Subset (6)

evidence_summarization · 4.64k rows

Split (1)

train · 4.64k rows

id int64 0 4.64k	task_type stringclasses 1 value	instruction_prompt stringclasses 1 value	question stringlengths 362 64.9k	answer stringclasses 5 values
4,600	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What were the findings regarding the effectiveness of transarterial embolisation (TAE) or transarterial chemoembolisation (TACE) compared to no intervention in people with liver metastases? Please answer this question based on the information provided below: Prospective randomized controlled trial of hepatic arterial embolization or infusion chemotherapy with 5-fluorouracil and degradable starch microspheres for colorectal liver metastases. Survival benefit from hepatic artery embolization (HAE) or hepatic arterial infusion chemotherapy (HAI) in patients with unresectable colorectal liver metastases has not previously been assessed in a randomized controlled trial. Sixty-one patients were randomized, 20 to receive no treatment, 22 to receive HAE, and 19 to receive HAI with 5-fluorouracil and degradable starch microspheres. Both treatments were acceptable to the patients in terms of low treatment morbidity rate. Median survival from diagnosis of metastases was 9.6 months for controls, 8.7 months for the HAE group and 13.0 months in the HAI group. There was no apparent survival benefit for the HAE group. The increased survival in the HAI group was observed in all the subgroups analysed but failed to reach statistical significance. The greatest observed benefit was achieved in the subgroup with less than 50 per cent hepatic replacement with tumour at presentation (median survival from diagnosis 10.0 months for controls, 10.2 months for HAE and 23.6 months for HAI); 36 per cent of patients developed extrahepatic disease recurrence. No significant benefit has been shown from either HAE or HAI, but a more carefully selected group of patients with only low volume hepatic disease may benefit from HAI therapy. Options: A: TAE and TACE significantly reduced mortality compared to no intervention. B: TAE and TACE showed no significant difference in mortality compared to no intervention. C: TAE and TACE significantly improved health-related quality of life compared to no intervention. D: TAE and TACE significantly reduced the time to progression of liver metastases compared to no intervention.	B
4,601	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the diagnostic accuracy of basal and/or stimulated calcitonin testing for detecting medullary thyroid cancer (MTC) in individuals with thyroid nodules? Please answer this question based on the information provided below: Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 5817 consecutive patients with thyroid nodules. CONTEXT: Routine serum calcitonin (CT) measurement in patients with thyroid nodules for diagnosis of medullary thyroid carcinoma (MTC) is controversial. OBJECTIVE: The objective of this study was to evaluate the diagnostic accuracy of systematic CT measurement in non-multiple endocrine neoplasia type 2 patients with nodular thyroid disease. SETTINGS: This study was conducted at a national healthcare system hospital (outpatient and inpatient sectors). SUBJECTS: Consecutive patients with nodular thyroid disease (n = 5817) were studied. MAIN OUTCOME MEASURES: Serum CT levels were measured under basal conditions, and when basal values were more than or equal to 20 and less than 100 pg/ml, testing was repeated after pentagastrin stimulation. Basal or stimulated levels more than 100 pg/ml were indication for surgery. RESULTS: Fifteen cases of MTC and seven of C cell hyperplasia (CCH) were identified. MTCs were diagnosed in all patients with basal CT more than 100 pg/ml. The four patients with basal CT more than or equal to 50 and less than 100 pg/ml included two diagnosed with MTC and two with CCH. In 10 patients with basal levels more than or equal to 20 and less than 50 pg/ml, histology confirmed the presence of MTC in four, four others had CCH, and the remaining two were negative for thyroid malignancy. Positive predictive values for basal CT levels in the preoperative diagnosis of MTC were: 23.1% for values more than or equal to 20 pg/ml, 100% for values more than 100 pg/ml, 25% for levels more than or equal to 50 and less than 100 pg/ml, and 8.3% for values more than or equal to 20 and less than 50 pg/ml. Positive predictive values for the pentagastrin test (>100 pg/ml) were 40% in the entire series. CONCLUSIONS: CT screening of thyroid nodules is a highly sensitive test for early diagnosis of MTC, but confirmatory stimulation testing is necessary in most cases to identify true positive increases. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. The survival rate of patients with medullary thyroid carcinoma (MTC) is significantly better in patients diagnosed and treated when the tumor is limited to the thyroid. In a pioneer study carried out in 1991, we demonstrated that routine measurement of serum calcitonin (CT) in nodular thyroid disease allowed the preoperative diagnosis of unsuspected sporadic MTC with better accuracy than routine fine needle aspiration cytology (FNAC). This finding has been confirmed in subsequent studies. In the present study we report the results of CT screening in 10,864 patients with thyroid nodular disease seen in the years 1991-1998 (group 1). We analyzed the prevalence of MTC and compared their outcomes with those of a historical group of patients (group 2) diagnosed before the introduction of CT screening (1970-1990). The prevalence of MTC found by CT screening in group 1 was 0.40% (44 patients). A positive CT test had a higher diagnostic sensitivity and specificity compared with FNAC. CT screening allowed the diagnosis of MTC at an earlier stage compared with group 2 (P = 0.004). Normalization of serum CT levels (undetectable) after surgery was more frequently observed in group 1. At the end of follow-up, complete remission was observed in 59% of group 1 and in 2.7% of group 2 (P = 0.0001). Our study confirms that MTC is not an infrequent finding among patients with thyroid nodules (nearly 1 in 250 patients). In addition, screening thyroid nodules with serum CT measurement allows the diagnosis and treatment of MTC at an earlier stage, resulting in a better outcome compared with MTC not detected by serum CT measurement. One of the reasons for this finding is that increasing the preoperative diagnostic accuracy of MTC prompts the surgeon to perform a more radical and possibly curative treatment. On this basis, routine measurement of basal serum CT levels should be considered an integral part of the diagnostic evaluation of thyroid nodules. Routine measurement of serum calcitonin in nodular thyroid diseases allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma. To assess whether routine measurement of serum calcitonin (CT) could improve the preoperative diagnosis of sporadic medullary thyroid carcinoma (MTC), 1385 consecutive patients presenting for nodular thyroid disease during the year 1991 were submitted to serum CT determination and fine needle aspiration cytology (FNAC). The clinical diagnosis was nontoxic nodular goiter in 1197 (86.4%) patients, toxic multinodular goiter in 65 (4.7%), autonomously functioning thyroid nodule (AFTN) in 64 (4.6%), and autoimmune thyroid disease (Graves' disease or Hashimoto's thyroiditis) with nodule(s) in 59 (4.3%). As controls, 177 patients with nonnodular thyroid disease and 32 normal subjects were also studied. Patients with FNAC suspicious of any kind of thyroid carcinoma and patients with elevated basal and pentagastrin-stimulated serum CT, regardless of the results of FNAC, were submitted to surgery. Eight (0.57%) patients (7 with nontoxic nodular goiter and 1 with AFTN) had elevated basal serum CT levels, ranging between 55-10,000 pg/mL. The pentagastrin test was abnormal in all of them. FNAC was suggestive of MTC in 2, thyroid carcinoma in 1, benign nodule in 3, and inadequate in 2. By histology, immunohistochemistry, and Northern blot analysis of total tumor RNAs, MTC was confirmed in all patients, including the 1 with AFTN, who had the association of microfollicular adenoma and a small MTC in the same lobe. After surgery, serum CT decreased to undetectable levels in 7 patients and remained undetectable in 6 of them during a mean follow-up of 22 months, although 1 of them had a positive response to pentagastrin. Forty-four patients in the group with normal serum CT levels had FNAC suspicious for differentiated thyroid carcinoma and were treated by surgery. Differentiated thyroid carcinoma, mostly papillary, was confirmed at histology in 43 subjects (3.1% of all thyroid nodules). In conclusion, the results of our study indicate that serum CT measurement is useful for the screening of sporadic MTC in patients with thyroid nodule(s). The prevalence of MTC, diagnosed by serum CT measurement in a 12-month period, among an unselected series of 1385 patients with nodular thyroid disease was surprisingly high: 0.57% of all thyroid nodules and 15.7% of all thyroid carcinomas. Serum CT measurement was superior to FNAC in suggesting the diagnosis of MTC and was devoid of falsely positive results. Increasing the diagnostic accuracy helped the surgeon to perform more radical treatment of MTC, thus achieving frequent normalization of postoperative serum CT levels. Whether this result indicates definitive cure remains to be established on the basis of longer follow-up.(ABSTRACT TRUNCATED AT 400 WORDS) Comparison of serum calcitonin and procalcitonin in detecting medullary thyroid carcinoma among patients with thyroid nodules. BACKGROUND: To prospectively evaluate the role of procalcitonin (PCT) in detecting or excluding medullary thyroid carcinoma (MTC) among patients with thyroid nodules and increased calcitonin (CT) levels. METHODS: Fourteen of 1236 patients referred for thyroid nodules had increased serum CT >10 pg/mL. A stimulation test with pentagastrin was done and both CT and PCT were measured after stimulation. All patients underwent thyroid ultrasound, fine-needle cytology and, if indicated, surgery with histological and immunohistochemical examination of the surgical specimens. RESULTS: After follow-up, two MTCs were found. These two patients had basal CT >100 pg/mL and detectable (>0.1 ng/mL) PCT, with 100% sensitivity. Pentagastrin stimulated CT achieved values above 100 pg/mL in two MTCs and in other two cases with no MTC outcome (50% PPV and 83% NPV). On the contrary, all patients with no MTC had both basal and stimulated undetectable PCT (100% PPV and 100% NPV). CONCLUSIONS: The addition of basal PCT measurement in patients with thyroid nodule(s) and increased CT may significantly improve accuracy of CT measurement without needing a PG stimulation test. Interpretation of serum calcitonin in patients with chronic autoimmune thyroiditis. Calcitonin (CT) is an important clinical marker for the diagnosis and follow-up of medullary thyroid carcinoma, although it is not absolutely specific. Some authors have reported C-cell hyperplasia in a number of thyroid specimens affected by Hashimoto's thyroiditis. The association between thyroiditis and hypercalcitoninemia is still controversial because some authors have reported low CT levels. The aim of this study is to evaluate the basal CT values in patients with and without thyroid autoimmunity. From May 2005 to February 2010, 1073 patients underwent ultrasonography-guided fine-needle aspiration cytology at the Thyroid Center of Sapienza University of Rome, with evaluation of basal serum FT4, FT3, TSH, and antithyroid peroxidase (anti-TPO) antibodies as well as CT levels. Forty-one patients presented a basal CT level above the reference upper limit. The mean serum CT was significantly lower in women than in men (4.28 ± 6.63 vs 7.50 ± 25.50 pg/ml; P<0.01). Basal serum CT was not significantly higher in patients showing anti-TPO Ab positivity (4.71 ± 6.46 vs 4.84 ± 13.11 pg/ml; P>0.05). Importantly, the rate of 'suspicious' CT values (above the 10 pg/ml cutoff) was not significantly different between patients with or without thyroid autoimmunity (3.9 vs 3.0%). Patients with hypercalcitoninemia suffering from chronic autoimmune thyroiditis should undergo the same clinical evaluation procedure as patients do without thyroid autoimmunity. Routine measurement of serum calcitonin is useful for early detection of medullary thyroid carcinoma in patients with nodular thyroid diseases. BACKGROUND: Medullary thyroid carcinoma (MTC) is characterized by a high concentration of serum calcitonin. Routine measurement of serum calcitonin concentration has been advocated for detection of MTC among patients with nodular thyroid diseases. However, a minimal to moderate increase of serum calcitonin concentration has been frequently observed in diseases other than MTC. Fine-needle aspiration cytology (FNAC) is not a reliable method for detection of MTC. Therefore, we evaluated the usefulness of routine measurement of serum calcitonin concentration in patients with nodular thyroid diseases, and studied the validity of pentagastrin stimulation test and FNAC in these patients. SUBJECTS AND METHODS: We performed routine measurement of serum calcitonin concentrations in 1,448 patients (male, 285, female, 1,163) with nodular thyroid diseases. The average age was 46 years (range, 14-86 years). Initial examination included thyroid examination, thyroid scan or ultrasonography, measurements of serum free triiodothyronine) (T3), free thyroxine (T4), thyrotropin (TSH) levels, and antithyroid autoantibodies. FNAC was performed in all patients who had palpable or visible thyroid nodule by ultrasonography, and pentagastrin stimulation test was performed in 39 patients who consented. Serum calcitonin concentration was measured with a two-site immunoradiometric assay using commercial kits. We also measured the serum calcitonin concentration in 407 healthy subjects without thyroid or nonthyroid diseases. RESULTS: Serum calcitonin concentration was 10 pg/mL or less in 403 normal subjects (99.0 percentile), and 11-13 pg/mL in the remaining 4 subjects. We found that 56 (3.87%) of 1,448 patients with nodular thyroid diseases had serum calcitonin level above 10 pg/mL. Ten patients (0.69%) with histologically confirmed MTC were detected by the routine measurement of serum calcitonin. The prevalence of MTC was 5.2% in 194 patients with thyroid carcinoma. Five of 10 patients with MTC had basal serum calcitonin level above 100 pg/mL. The remaining 5 patients had minimal or moderate elevation of basal serum calcitonin (range, 12-86 pg/mL). Serum calcitonin concentration increased to more than 100 pg/mL by pentagastrin in all patients with MTC (2.4- to 37.7-fold increase). FNAC suggested MTC in only 2 patients (22.2%), and failed to diagnose MTC in 7 patients. FNAC was not performed in 1 patient with MTC, because he had no visible mass by ultrasonography. CONCLUSION: These results suggested that routine measurement of serum calcitonin is useful in the early detection of MTC among patients with nodular thyroid diseases. Pentagastrin stimulation test may also be a reliable way for evaluating thyroid nodular patients with mild or moderate elevation of serum calcitonin concentrations. However, FNAC was not sensitive in detecting MTC. We recommend routine measurement of serum calcitonin concentration in patients with nodular thyroid diseases. Benefit of measuring basal serum calcitonin to detect medullary thyroid carcinoma in a Danish population with a high prevalence of thyroid nodules. BACKGROUND: Routine measurement of serum calcitonin to detect medullary thyroid carcinoma (MTC) continues to be fiercely debated, although less attention has been paid to the positive predictive value (PPV) of this method. METHODS: We collected data from 959 patients with nontoxic nodular goiter; thyroidectomy was performed in 307 of these patients. RESULTS: Thirty-nine patients had elevated serum calcitonin; 6 of these patients had MTC detected by the initial diagnostic setup. No additional patient in the cohort was registered in the Danish Thyroid Cancer Database, reflecting that all patients with MTC were classified correctly initially. The sensitivity of serum calcitonin for detection of MTC was 100%, the specificity was 95.3%, the positive predictive value was 15.4%, and the negative predictive value was 100%. CONCLUSION: Serum calcitonin has high sensitivity and specificity for detection of MTC. The low PPV might lead to unnecessary thyroid surgery. Thus, the result of serum calcitonin measurement should always be interpreted in the context of other clinical variables. Calcitonin screening and pentagastrin testing: predictive value for the diagnosis of medullary carcinoma in nodular thyroid disease. CONTEXT: Serum calcitonin (hCT) measurement may be useful for detecting medullary thyroid carcinoma (MTC), but the routine use of hCT after pentagastrin stimulation to screen patients with nodular thyroid disease remains controversial. PATIENTS: A total of 1007 patients (567 females and 440 males) with nodular thyroid disease and a mean age of 55+/-14 (mean+/-S.D.) years were included in the study. All patients did not have impaired renal function, bacterial infection, alcohol and drug abuse, pseudohypoparathyroidism, or proton-pump inhibitor therapy. Individuals referred with known elevation of hCT, Graves' disease, or autoimmune thyroid disease were not considered or included in this investigation. METHODS: Serum hCT levels were determined under basal conditions, and when basal values were >or=10 and <100 pg/ml, testing was repeated after pentagastrin stimulation. Patients with basal or stimulated levels >100 pg/ml were referred for surgery. RESULTS: hCT levels >10 pg/ml were increased in 17 patients (1.7%). One patient had a basal hCT level of 4400 pg/ml with a histological confirmation of a MTC. In this patient, pentagastrin test was not performed. Sixteen patients with basal hCT between 10 and 100 pg/ml underwent pentagastrin-stimulated hCT measurement. Of 16 patients, 4 had stimulated hCT>100 pg/ml. Of 17 patients with hCT>10 pg/ml, 2 had MTC, and of 17 patients, 3 had C-cell hyperplasia. In total, two patients (0.20%) had a histologically verified MTC. CONCLUSIONS: Basal hCT measurement together with pentagastrin-stimulated hCT measurement in cases of basal hCT>10 pg/ml detects MTC in 0.20% of patients with nodular thyroid disease. Whether this high incidence of MTC has major implications or not has to be discussed, but it should be considered as a useful and recommended tool for early detection of MTC and to save patients' life. Frequency and relevance of elevated calcitonin levels in patients with neoplastic and nonneoplastic thyroid disease and in healthy subjects. Routine measurement of serum calcitonin (CT) has been recently proposed for all patients with neoplastic thyroid disease to detect clinically occult medullary thyroid carcinoma (MTC). Data on the prevalence of elevated CT levels in nonneoplastic thyroid disease or in healthy subjects have not been reported to date. Four hundred and fourteen consecutive patients with suspected thyroid disease and 362 healthy controls underwent thyroid examination with measurement of basal serum CT. Whenever serum CT was 10 pg/ml or more, a pentagastrin (PG) stimulation test was performed. Twenty-eight of 414 patients (6.8%) showed elevated basal serum CT levels, 15 of them with nonneoplastic thyroid disease, and the remaining 13 subjects with neoplastic thyroid disease. Four patients with abnormal PG testing (stimulated CT, > or = 100 pg/ml) were identified. Three of them had biochemical and sonographical evidence of thyroiditis. Elevated basal CT levels were significantly more frequent in patients with Hashimoto's thyroiditis (HT; P < 0.05). One female patient with HT had a 5-mm nodule, which was classified as MTC. None of the 6 out of 362 healthy controls with elevated basal CT (1.7%) presented an abnormal PG test. Our data suggest that basal CT measurements can be of use in the detection/screening of MTC not only in subjects with neoplastic thyroid disorders, but also in patients with immunological evidence of HT. They also confirm earlier reports on the essential value of PG stimulation testing, even when basal plasma CT levels are only modestly elevated, with regard to establishing the diagnosis of MTC or its premalignant associated conditions (micro-MTC and neoplastic C cell hyperplasia). Evaluation of routine basal serum calcitonin measurement for early diagnosis of medullary thyroid carcinoma in seven hundred seventy-three patients with nodular goiter. The aims of the study were to identify medullary thyroid cancer (MTC) in its earliest stages by screening patients with basal calcitonin measurements and to determine whether basal serum calcitonin measurements should be a part of the routine evaluation of a nodular goiter. Basal serum calcitonin levels were obtained from 75 patients (female:male 57:18, mean age 42.8 years, range with 18-76 years) with nonnodular thyroid disease as controls. Their mean basal calcitonin level was 7.8+/-0.4 pg/mL with a range of 5-27 pg/mL. Seven hundred seventy-three patients with nodular goiter were included in the study (female:male 586:187) with the mean age of 46.1 years (range 17-78). Four patients had elevated basal serum calcitonin levels ranging between 150-1000 pg/mL. These 4 patients underwent surgery. MTC was confirmed by histopathology in all 4. One patient's mother and brother were also diagnosed as MTC as a result of family screening. Basal serum calcitonin levels were higher than 150 pg/mL in these patients. Fine needle aspiration biopsy (FNAB) of 2 of 4 MTC patients were incorrectly diagnosed as papillary carcinoma; another had malignant cytology and the fourth had benign cytology. None were diagnosed as MTC on the basis of FNAB. In conclusion, calcitonin measurement is an effective method for the diagnosis of MTC. Measurement of basal calcitonin levels in patients with malignant or suspicious FNAB may be a cost-effective approach to screen for MTC. High basal serum calcitonin levels increase the chance of curative therapy by diagnosing MTC in the early stages. It is superior to FNAB for diagnosis of MTC. Value of routine measurement of serum calcitonin concentrations in patients with nodular thyroid disease: A multicenter study. BACKGROUND: The routine measurement of serum calcitonin (CT) has been proposed for patients with nodular thyroid disease (NTD), to detect unsuspected medullary thyroid carcinoma (MTC) before surgery. OBJECTIVE: To assess the prevalence of hypercalcitoninemia and MTC in NTD patients; to compare the ability of CT measurement and fine needle aspiration cytology (FNAC) to predict MTC; to identify age groups of NTD patients who should be better candidates than others to undergo routine measurement of CT. PATIENTS AND METHODS: 1425 consecutive patients, referred from April 1, 2003, through March 31, 2004, to four Italian endocrine centers due to NTD, were grouped depending on age, and underwent basal and, in some cases, pentagastrin (Pg)-stimulated CT measurement, FNAC and, when indicated, surgery. Serum CT concentrations were measured by an immunoluminometric assay (ILMA). RESULTS: Hypercalcitoninemia was found in 23 out of 1425 patients. MTC was discovered in 9 patients, all >40 yr old and showing high CT levels. Sensitivity of basal and Pg-stimulated CT to predict MTC before surgery was 100% for both tests, whereas specificity was 95 and 93%, respectively. CT specificity reached 100% when a cutoff value of 20 pg/ml was taken. FNAC showed an overall 86% sensitivity. When >10 mm MTC nodules were considered, FNAC sensitivity approached 100%. On the contrary, a correct cytological diagnosis was obtained in only one out of five patients with <10 mm MTC nodules (microMTC); in one patient with histologically proved microMTC, FNAC even demonstrated a benign lesion. Hypercalcitoninemia or MTC were associated with chronic thyroiditis in 30 or 33% of cases, respectively. C-cell hyperplasia was found in 57% of hypercalcitoninemic patients without MTC. CONCLUSIONS: Basal CT measurement detects elevated CT values in 1.6% of NTD patients. Although CT is not a specific marker of MTC, its routine measurement represents a useful tool in the pre-operative evaluation of NTD patients, particularly those >40 yr old presenting with nodules <10 mm, even when FNAC does not show malignant features. To our knowledge, this is the first trial using ILMA to assess the ability of pre-operative CT measurement to predict MTC in a large series of NTD patients. Prevalence of sporadic medullary thyroid carcinoma: the importance of routine measurement of serum calcitonin in the diagnostic evaluation of thyroid nodules. OBJECTIVE: The prevalence of sporadic forms of medullary thyroid carcinoma (MTC) has been studied in patients living in an area of moderate iodine deficiency. Such forms of MTC are usually diagnosed after surgery and have little chance of definitive cure. Using the measurement of basal serum calcitonin (CT) levels in a large series of patients with both thyroid disease and normal 24-hour urinary iodine excretion, we assessed the prevalence of MTC and, in patients affected with the disease, we also evaluated the stage of the disease according to surgical findings and post surgical plasma CT levels. PATIENTS: A prospective study of 657 patients with thyroid disease (469 with nodular and 188 with non-nodular thyroid disease). As controls, 40 normal subjects were also studied. MEASUREMENTS: In all patients: (1) measurement of basal serum CT, free T4, total T3, TSH levels and serum TSH-receptor, peroxidase and thyroglobulin (Tg) antibody concentrations, (2) thyroid ultrasonography, (3) fine needle aspiration cytology (FNAC). In patients with increased basal CT levels: (1) measurement of serum CT levels during pentagastrin test prior to surgery, (2) histological examination and immunostaining with both anti-CT and anti-Tg antibodies of all the nodular thyroid tissue surgically removed, (3) measurement of basal and pentagastrin stimulated serum CT values after surgery. RESULTS: All the patients with non-nodular thyroid disease had normal basal CT levels. Four patients (0.84%) with nodular thyroid disease (2 with uninodular and 2 with multinodular goitre) had both elevated basal and pentagastrin stimulated CT levels. In the two patients with uninodular goitre, FNAC was suggestive of MTC in 1 (nodular diameter 8.0 cm) and of follicular carcinoma in 1 (nodular diameter 2.5 cm). Histological examination of the nodules confirmed these histotypes. Immunostaining with anti-CT antibodies was positive in the former patient but also in the latter. FNAC was suggestive of benign adenomatous tissues in the two patients with multinodular goitre. Histological examination of all the thyroid nodules confirmed the cytological findings. However, serial sections through the gland in each of these two patients showed an occult follicular carcinoma which had, however, positive staining with anti-CT antibodies. Furthermore, immunostaining with anti-Tg antibodies was negative in the patient with MTC but positive in the 3 patients with follicular carcinoma. Finally, both basal and pentagastrin stimulated CT levels remained elevated after total thyroidectomy only in the patient with FNAC suggesting MTC. CONCLUSIONS: This study demonstrates a surprisingly high prevalence of sporadic forms of medullary thyroid carcinoma in patients with nodular thyroid disease. Such forms of medullary thyroid carcinoma seem to be unrelated to iodine intake and may be pure or mixed with a follicular carcinoma. In these mixed thyroid carcinomas, only the neoplastic follicular pattern was seen on both cytological and histological examination. Routine measurements of serum calcitonin levels should therefore be considered an integral part of the diagnostic evaluation of thyroid nodules. Indeed, increasing the accuracy of diagnosis of medullary thyroid carcinoma encourages the surgeon to perform more radical treatment, thus achieving more frequent normalization of post-operative serum calcitonin levels. Calculation and validation of a plasma calcitonin limit for early detection of medullary thyroid carcinoma in nodular thyroid disease. BACKGROUND: The early diagnosis of medullary thyroid carcinoma (MTC) is crucial for effective therapy. Elevated plasma calcitonin concentrations (pCT-Cs) are generally a specific and sensitive indicator for C-cell hyperplasia or MTC. The presence of thyroid nodules raises the possibility of MTC. Hence, in endemic goiter regions, there is a need for information regarding the pCT-C values that are indicative of C-cell hyperplasia or MTC. The aim of this study, therefore, was to determine an upper pCT-C to distinguish patients with and without MTC in a collective with nodular thyroid disease, and to give an estimation of the prevalence of MTC in an endemic goiter area. METHODS: Basal pCT-C was measured in 21,928 patients with thyroid nodules living in central Germany, an area with endemic goiter due to previous iodine deficiency. In 218 subjects with pCT-Cs exceeding 10 ng/L, stimulated pCT-C was additionally determined, as suggested by the German consensus recommendation. A nominal normal range for basal pCT-C was calculated with data from 21,900 subjects without known MTC. The predicted upper limit was then validated using the known diagnoses of 376 patients with pCT-Cs exceeding 10 ng/L, 28 of whom presented with MTC. RESULTS: For basal pCT-C, calculation of the three-sigma borders after logarithmic transformation revealed upper limits of the nominal normal range of 14.6 ng/L in females and 32.8 ng/L in males, respectively. However, three male patients with small MTCs had basal pCT-Cs between 15 and 33 ng/L. None of the patients with MTC had a basal pCT-C below 15 ng/L or an increase in pCT-C after pentagastrin stimulation that was less than 80 ng/L. In the basal pCT-C range between 15 and 50 ng/L (n = 192; eight with MTC), the positive predictive value for the detection of MTC was 4% in our group. Applying an upper limit for basal pCT-C of 15 ng/L in both sexes, 329 of the total of 21,928 patients exceeded this range. Among these, the final outcome is known in 231 subjects, including all 28 MTCs. CONCLUSIONS: An upper limit of 15 ng/L instead of 10 ng/L for basal pCT-C is able to detect all MTC and reduce false-positive cases. The prevalence of MTC in nodular thyroid disease in our group was approximately 1.8 per thousand. Calcitonin screening in patients with thyroid nodules. Diagnostic value. AIM: The positive predictive value (PPV) of a slightly elevated basal calcitonin (CT) for the diagnosis of medullary thyroid cancer (MTC) is still under debate. PATIENTS, METHODS: A total of 11270 patients with thyroid nodules underwent calcitonin screening. Patients with known elevation of CT, renal insufficiency, bacterial infection, alcohol abuse, proton-pump inhibitor therapy or autoimmune thyroid disease were excluded from further analysis. Serum CT was determined by the solid-phase, enzyme-labeled, two-site chemiluminescent immunoassay Immulite 2000. If possible, a pentagastrin test was done to differentiate cases of hypercalcitoninaemia. RESULTS: Hypercalcitoninsemia was found in 32 patients. 20 patients underwent surgery. In 10 patients a MTC was found. The PPV of hypercalcitoninaemia for MTC was 31%. The PPV increased to 50% for those patients who underwent surgery (10/20). A subgroup of 26 patients presented with basal CT between 13 and 50 pg/ml, 14 of them underwent surgery, in 4 cases evidence of MTC was revealed. This resulted in a PPV of 15% (4/26), although the value increased to 28% when only surgically treated patients were considered (4/14). CONCLUSION: Taking all clinical data into account, calcitonin screening has an acceptable PPV for medullary thyroid cancer in patients with thyroid nodules. Therefore, we recommend calcitonin screening in centers for thyroid disorders. Calcitonin measurements for early detection of medullary thyroid carcinoma or its premalignant conditions in Hashimoto's thyroiditis. The measurement of basal serum calcitonin (CT) in patients with evidence of Hashimoto's thyroiditis (HT) has been proposed in a recent study demonstrating an increased prevalence of elevated basal and stimulated CT. The aim of this study was to evaluate the frequency and relevance of elevated CT levels in HT. The basal sera CT were measured in 568 consecutive HT patients using a chemiluminescent immuno-assay. Whenever the serum CT was > 10 pg/ml, a pentagastrin (PG) stimulation test was performed. Two patients with abnormal/pathological PG tests were identified. Total thyroidectomy and lymph node dissection revealed for the first patient medullary thyroid carcinoma (MTC) and for the second patient C cell hyperplasia (CCH), together with papillary thyroid carcinoma. Our data showed a low prevalence of MTC and its premalignant condition CCH in HT patients; nevertheless, the patient with MTC presented lymph node metastasis. The fact that both cases presented without evidence of nodular thyroid disease highlights the persistent diagnostic dilemma of CT screening programs. Early diagnosis and curative therapy of medullary thyroid carcinoma by routine measurement of serum calcitonin in patients with thyroid disorders. To identify patients with medullary thyroid carcinoma (MTC) at a potentially curable stage of the disease, serum concentrations of calcitonin (hCT) were determined in 14,000 patients (including 10,158 patients with thyroid nodules) referred to a thyroid outpatient clinic. Excluding patients in whom elevated basal hCT concentrations had already been known at the time of their referral, 507 patients with thyroid nodules presented basal concentrations of hCT of more than 10 pg/ml. Following stimulation by IV pentagastrin (0.5 microg/kg BW), hCT concentrations of more than 100 pg/ml were seen in 103 patients. This group included 32 new cases of MTC (29 patients with sporadic MTC and 3 new index cases of the familial form) and 43 patients with C cell hyperplasia (CCH). Among the 3,843 patients without thyroid nodules, 2 were found to harbor sporadic MTC while 4 had CCH. As compared to 1.1 cases of MTC per 1,000 patients with nodular thyroid diseases diagnosed in our institution before hCT screening was begun, 3.2 cases of MTC per 1,000 patients were identified when hCT was determined in all patients with thyroid nodules. The determination of hCT in all patients with thyroid nodular disease facilitates the timely diagnosis of MTC, thus providing the chance of curative surgery. Routine measurement of plasma calcitonin in nodular thyroid diseases. In a prospective study, plasma concentrations of human calcitonin (hCT) were determined in 1062 consecutive patients with thyroid nodular disease. Basal plasma hCT was above the normal range (>6 pg/mL) in 55 patients and was elevated up to more than 100 pg/mL (range, 127-5459) in 3 of these 55 patients. A pentagastrin-induced rise in hCT up to more than 100 pg/mL was observed in only 1 of 38 patients with a basal concentration of hCT between 5-10 pg/mL, but was found in 10 of 31 patients with basal hCT ranging from 10-100 pg/mL. Histologically, 7 of the 14 patients with either basal or stimulated plasma concentrations of hCT above 100 pg/mL presented C cell hyperplasia, which in one case showed histological transition into a small (diameter, 3 mm) medullary thyroid carcinoma (MTC). Including this patient, MTC was found in 6 of the 12 patients. We conclude that the routine determination of hCT in all patients with thyroid nodular disease should be supplemented by pentagastrin-stimulation when the basal hCT concentration exceeds 10 pg/mL. Patients with basal and/or stimulated plasma CT concentrations of more than 100 pg/mL should be operated on because they run a substantial risk to suffer either MTC or C cell hyperplasia, a potentially precancerous condition. This will increase the chance of a timely diagnosis of MTC and provide the chance of curative surgery. Options: A: Both basal and combined basal and stimulated calcitonin testing have high sensitivity and specificity, but the low prevalence of MTC results in a low positive predictive value (PPV) for basal calcitonin testing. B: Basal calcitonin testing has high sensitivity but low specificity, while combined basal and stimulated calcitonin testing has low sensitivity and high specificity. C: Both basal and combined basal and stimulated calcitonin testing have low sensitivity and specificity, making them unreliable for detecting MTC. D: Basal calcitonin testing has low sensitivity and high specificity, while combined basal and stimulated calcitonin testing has high sensitivity and low specificity.	A
4,602	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What were the findings regarding the effectiveness and safety of diaphragm-triggered non-invasive respiratory support (NIV-NAVA) in preterm infants compared to other non-invasive respiratory support methods? Please answer this question based on the information provided below: Feasibility and physiological effects of noninvasive neurally adjusted ventilatory assist in preterm infants. BackgroundNoninvasive neurally adjusted ventilator assist (NIV-NAVA) was introduced to our clinical practice via a pilot and a randomized observational study to assess its safety, feasibility, and short-term physiological effects.MethodsThe pilot protocol applied NIV-NAVA to 11 infants on nasal CPAP, high-flow nasal cannula, or nasal intermittent mandatory ventilation (NIMV), in multiple 2- to 4-h periods of NIV-NAVA for comparison. This provided the necessary data to design a randomized, controlled observational crossover study in eight additional infants to compare the physiological effects of NIV-NAVA with NIMV during 2-h steady-state conditions. We recorded the peak inspiratory pressure (PIP), FiO Non-invasive neurally adjusted ventilatory assist in preterm infants: a randomised phase II crossover trial. OBJECTIVE: To compare non-invasive ventilation neurally adjusted ventilatory assist (NIV-NAVA) and non-invasive pressure support (NIV-PS) in preterm infants on patient-ventilator synchrony. DESIGN: A randomised phase II crossover trial. SETTING: Neonatal intensive care units of two tertiary university hospitals in Korea. PATIENTS: Preterm infants born <32 weeks. INTERVENTION: NIV-NAVA and NIV-PS were applied in random order after ventilator weaning. Data were recorded for sequential 5 min periods after 10 min applications of each mode. MAIN OUTCOME MEASURES: The electrical activity of the diaphragm (Edi), ventilator flow and pressure curves were compared to examine the trigger delay (primary outcome) and other parameters of patient-ventilator interaction (secondary outcomes) for each period. RESULTS: Fifteen infants completed the protocol. Trigger delay (35.2±8.3 vs 294.6±101.9 ms, p<0.001), ventilator inspiratory time (423.3±87.1 vs 534.0±165.5 ms, p=0.009) and inspiratory time in excess (32.3±8.3% vs 294.6±101.9%, p=0.001) were lower during NIV-NAVA compared with NIV-PS. Maximum Edi (12.6±6.3 vs 16.6±8.7 μV, p=0.003), swing Edi (8.8±4.8 vs 12.2±8.7 μV, p=0.012) and peak inspiratory pressure (12.3±1.5 vs 14.7±2.7 cm H2O, p=0.003) were also lower during NIV-NAVA. The main asynchrony events during NIV-PS were ineffective efforts and autotriggering. All types of asynchronies except double triggering were reduced with NIV-NAVA. Asynchrony index was significantly lower during NIV-NAVA compared with NIV-PS (p<0.001). No significant differences in leakage, expiratory tidal volume or minute ventilation were observed, but the respiratory rate was lower during NIV-PS than during NIV-NAVA. CONCLUSIONS: NAVA improved patient-ventilator synchrony and diaphragmatic unloading in preterm infants during non-invasive nasal ventilation even in the presence of large air leaks. TRIAL REGISTRATION NUMBER: Registered with http://www.clinicaltrials.gov (NCT01877720). Options: A: NIV-NAVA significantly reduced the failure of respiratory support modality compared to NIPPV. B: NIV-NAVA showed no significant difference in the failure of respiratory support modality compared to NIPPV. C: NIV-NAVA significantly increased the failure of respiratory support modality compared to NIPPV. D: NIV-NAVA was found to be significantly more effective and safer than other non-invasive respiratory support methods.	B
4,603	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What were the findings regarding the effectiveness and safety of postnatal corticosteroids in treating transient tachypnoea of the newborn (TTN) in infants born at 34 weeks' gestational age or more? Please answer this question based on the information provided below: Inhaled corticosteroids in transient tachypnea of the newborn: A randomized, placebo-controlled study. OBJECTIVE: Prenatal corticosteroids were shown to reduce the respiratory complication in late preterm infants. Our objective was to determine if early inhaled corticosteroids could alleviate the respiratory distress and morbidity in late preterm and term neonates with transient tachypnea of the newborn (TTN). STUDY DESIGN: Double-blind, randomized placebo-controlled, multicenter pilot study. Infants born at >34 weeks gestational age with TTN at 4 h of age were randomized to two doses, 12 h apart, of inhaled Budesonide 1000 μg/dose or placebo within 6 h from delivery. Analysis was done by intention to treat. RESULTS: The study (n = 24) and control (n = 25) groups were comparable in birth characteristics (gestational age: 36.8 ± 1.9 vs 36.4 ± 1.8 weeks) and clinical condition at the time of recruitment (vital signs, clinical score, ventilation support, and blood gases). There was no difference between the study and control groups in clinical score (based on grunting, retractions, ala nasi, and respiratory rate) at recruitment and at 12, 24, and 48 h after the first inhalation (4.3 ± 1.6 vs 4.1 ± 2.1; 1.9 ± 1.8 vs 1.5 ± 1.7; 1.1 ± 1.4 vs 1.3 ± 1.6; 0.5 ± 0.8 vs 0.6 ± 1.0; respectively). Respiratory support at each time point, time to spontaneous unsupported breathing (67.4 ± 74.1 vs 75.2 ± 95.2 h), time to full feeds (86.7 ± 68.7 vs 84.3 ± 66.6 h) and length of stay (9.9 ± 5.5 vs 12.4 ± 8.0 days) did not differ between the groups. We did not detect any side effects. CONCLUSIONS: Our pilot study was unable to detect a beneficial effect of early administration of inhaled steroids on the clinical course of TTN in late preterm and term infants. Options: A: Postnatal corticosteroids significantly reduced the need for nasal continuous positive airway pressure and mechanical ventilation. B: Postnatal corticosteroids significantly increased the need for nasal continuous positive airway pressure and mechanical ventilation. C: There were no significant differences between postnatal corticosteroids and placebo in terms of need for nasal continuous positive airway pressure and mechanical ventilation. D: Postnatal corticosteroids significantly reduced the duration of hospital stay for infants with TTN.	C
4,604	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the current understanding of the effectiveness and safety of intense pulsed light (IPL) therapy for treating meibomian gland dysfunction (MGD) and its associated dry eye symptoms? Please answer this question based on the information provided below: Therapeutic efficacy of intense pulsed light in patients with refractory meibomian gland dysfunction. PURPOSE: To evaluate the efficacy and safety of intense pulsed light (IPL) combined with meibomian gland expression (MGX) for treatment of refractory meibomian gland dysfunction (MGD). METHODS: Ninety eyes of 45 patients were randomly assigned to receive either the combination of IPL and MGX or MGX alone (control). Each eye underwent eight treatment sessions at 3-week intervals. Parameters were evaluated before and during treatment as well as at 3-11 weeks after the last treatment session. Measured parameters included the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire score, noninvasive breakup time (NIBUT), fluorescein breakup time (BUT), lipid layer grade, lipid layer thickness (LLT), lid margin abnormalities, corneal and conjunctival fluorescein staining (CFS) score, meibum grade, and meiboscore. RESULTS: A significant improvement in lipid layer grade was apparent in the IPL-MGX group from 6 to 32 weeks after treatment onset (adjusted P < 0.001) but was not observed in the control group. The IPL-MGX group also showed significant improvements in LLT, NIBUT, BUT, lid margin abnormalities, and meibum grade compared with the control group at 24 and 32 weeks (adjusted P < 0.001) as well as significant improvements in the SPEED score at 32 weeks (adjusted P = 0.044) and in CFS score at 24 (adjusted P = 0.015) and 32 (adjusted P = 0.006) weeks. CONCLUSIONS: The combination of IPL and MGX improved homeostasis of the tear film and ameliorated ocular symptoms in patients with refractory MGD and is thus a promising modality for treatment of this condition. Prospective trial of intense pulsed light for the treatment of meibomian gland dysfunction. PURPOSE: To evaluate the effect of intense pulsed light (IPL) applied to the periocular area for meibomian gland dysfunction (MGD) in a prospective, double-masked, placebo-controlled, paired-eye study. METHODS: Twenty-eight participants underwent IPL treatment, with homogeneously sequenced light pulses delivered to one eye and placebo treatment to the partner control eye at 1, 15, and 45 days following baseline (BL) evaluation. Lipid layer grade (LLG), noninvasive tear break-up time (NIBUT), tear evaporation rate (TER), tear meniscus height (TMH), and subjective symptom score using visual analogue scales (VAS) were compared with BL and control values at each visit. RESULTS: Lipid layer grade improved significantly from BL to Day (D) 45 in the treated eye (P < 0.001), but not the control eye (P = 0.714), with 82% of treated eyes improving by at least one LLG. Noninvasive tear break-up time also improved significantly from BL to D45 in the treated (P < 0.001) but not in the control eye (P = 0.056) and was significantly longer than in the treated eye at D45 (14.1 ± 9.8 seconds versus 8.6 ± 8.2 seconds, P < 0.001). The tear evaporation rate was not different in the treated eye compared with the control eye at any visit. Tear meniscus height did not change from BL in either eye (P > 0.05). Visual analog scale symptom scores improved from BL in the treated (P = 0.015), but not the control eye (P = 0.245), with 86% of participants noting reduced symptoms in the treated eye by D45. CONCLUSIONS: Intense pulsed light with multiple sculpted pulses shows therapeutic potential for MGD, improving tear film quality and reducing symptoms of dry eye. ( https://www.anzctr.org.au number, ACTRN12614000162617.). Prospective trial of intense pulsed light for the treatment of meibomian gland dysfunction. PURPOSE: To evaluate the effect of intense pulsed light (IPL) applied to the periocular area for meibomian gland dysfunction (MGD) in a prospective, double-masked, placebo-controlled, paired-eye study. METHODS: Twenty-eight participants underwent IPL treatment, with homogeneously sequenced light pulses delivered to one eye and placebo treatment to the partner control eye at 1, 15, and 45 days following baseline (BL) evaluation. Lipid layer grade (LLG), noninvasive tear break-up time (NIBUT), tear evaporation rate (TER), tear meniscus height (TMH), and subjective symptom score using visual analogue scales (VAS) were compared with BL and control values at each visit. RESULTS: Lipid layer grade improved significantly from BL to Day (D) 45 in the treated eye (P < 0.001), but not the control eye (P = 0.714), with 82% of treated eyes improving by at least one LLG. Noninvasive tear break-up time also improved significantly from BL to D45 in the treated (P < 0.001) but not in the control eye (P = 0.056) and was significantly longer than in the treated eye at D45 (14.1 ± 9.8 seconds versus 8.6 ± 8.2 seconds, P < 0.001). The tear evaporation rate was not different in the treated eye compared with the control eye at any visit. Tear meniscus height did not change from BL in either eye (P > 0.05). Visual analog scale symptom scores improved from BL in the treated (P = 0.015), but not the control eye (P = 0.245), with 86% of participants noting reduced symptoms in the treated eye by D45. CONCLUSIONS: Intense pulsed light with multiple sculpted pulses shows therapeutic potential for MGD, improving tear film quality and reducing symptoms of dry eye. ( https://www.anzctr.org.au number, ACTRN12614000162617.). Analysis of Cytokine Levels in Tears and Clinical Correlations After Intense Pulsed Light Treating Meibomian Gland Dysfunction. PURPOSE: To investigate the change from baseline of inflammatory markers in tears of dry eye disease (DED) subjects owing to meibomian gland dysfunction (MGD) after intense pulsed light (IPL) treatment and meibomian gland expression (MGE) compared to sham treatment, and the correlations with ocular surface parameters. DESIGN: Randomized, double-masked, controlled study. METHODS: Those randomized into the active treatment arm received 3 consecutive treatments (14∼16 J/cm RESULTS: All of the inflammatory markers declined in value compared to baselines. IL-17A and IL-6 showed statistically significant decreases compared to sham treatment at each measured time point. PGE2 showed statistically significant decreases compared to sham at week 12. Results showed that the expressions of IL-17A and IL-6 correlated well with ocular surface parameters of the lower eyelid before IPL. The changed values of IL-6 and PGE2 in tears correlated with the changed values of partial ocular surface parameters after IPL treatment in study eyes, respectively. CONCLUSIONS: The study results suggest that IPL can significantly reduce inflammatory markers in tears of patients suffering with DED owing to MGD after IPL treatment. These findings indicate that IL-17A and IL-6 play roles in the pathogenesis of DED owing to MGD, and the reduction of the inflammatory factors is consistent with the improvement of partial clinical symptoms and signs. Long-Term Effects of Intense Pulsed Light Combined with Meibomian Gland Expression in the Treatment of Meibomian Gland Dysfunction. OBJECTIVE: To evaluate the long-term effects of intense pulsed light (IPL) combined with meibomian gland expression (MGX) in the treatment of meibomian gland dysfunction (MGD). BACKGROUND: Although IPL has been proven to be effective in the treatment of MGD, any report regarding its long-term efficacy is unavailable by now. METHODS: The randomly selected study eye received a series of three IPL treatments that were applied directly on eyelids with an interval of 4 weeks (treatment energy, 14-16 J/cm RESULTS: In the study eyes, MGYSS of both the upper and lower eyelids and TBUT improved at 1, 3, 6 months after treatments (p < 0.01). MGYSS in lower eyelids continued to improve at 9 months (p < 0.05). The changes in MGYSS and TBUT after treatment were larger in the study eyes than in the control eyes at 1, 3, 6 months (p < 0.01), but no difference at 9 months (p > 0.05). The percentage improvement in the MGYSS of lower eyelids after treatment was higher than that of upper eyelids. CONCLUSIONS: Three consecutive IPL treatments combined with MGX improved MG secretion function and TBUT by 6 months after treatment in MGD patients. The improvement in MG secretion function was greater in the lower eyelid than in the upper eyelid. Intense Pulsed Light Applied Directly on Eyelids Combined with Meibomian Gland Expression to Treat Meibomian Gland Dysfunction. OBJECTIVE: To determine the efficacy and safety of intense pulsed light (IPL) applied directly on the eyelids and meibomian gland expression (MGX) in treating meibomian gland dysfunction (MGD). BACKGROUND: IPL application on the periocular skin effectively improves meibomian gland secretion and tear film break-up time (TBUT) in patients with MGD/dry eye. METHODS: This prospective, randomized, double-masked, controlled study involved 44 patients. One eye was randomly selected for IPL treatment; the other served as a control. Study eyes received three IPL treatments at 4-week intervals; IPL was applied directly on the eyelids, and the eye was protected with a Jaeger lid plate. Control eyes received sham IPL treatments. Both eyes received MGX and artificial tears. Meibomian gland yielding secretion score (MGYSS), TBUT, Standard Patient Evaluation of Eye Dryness (SPEED), cornea fluorescein staining (CFS), meibography, best corrected visual acuity (BCVA), intraocular pressure (IOP), and fundus examination were performed. RESULTS: Compared to the baseline, MGYSS, TBUT, and SPEED and CFS scores improved in the study eyes, while only SPEED and CFS scores improved in the control eyes (p < 0.001 for all). Changes in MGYSS and TBUT were higher in the study eyes than in the control eyes (p < 0.05), but changes in SPEED and CFS scores were similar (p > 0.05). BCVA and IOP improved in both the study and control eyes (p < 0.05). Five patients experienced mild pain and burning during IPL treatment. One patient suffered partial eyelash loss. CONCLUSIONS: IPL combined with MGX safely and effectively treated MGD. [Evaluation of short-term effect of intense pulsed light combined with meibomian gland expression in the treatment of meibomian gland dysfunction]. Options: A: IPL therapy is proven to significantly reduce dry eye symptoms and improve clinical parameters with high certainty. B: There is a scarcity of high-certainty evidence, making the effectiveness and safety of IPL therapy for MGD uncertain. C: IPL therapy has been shown to have no effect on dry eye symptoms and is associated with significant adverse events. D: IPL therapy is widely accepted as the best treatment for MGD, with clear evidence supporting its safety and effectiveness.	B
4,605	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What were the findings regarding the effectiveness of initial sustained lung inflation (SLI) compared to standard inflations in newborn infants receiving resuscitation with intermittent positive pressure ventilation (PPV) in terms of mortality and respiratory outcomes? Please answer this question based on the information provided below: Sustained lung inflation at birth for preterm infants at risk of respiratory distress syndrome: The proper pressure and duration. BACKGROUND: Variations exist among the administered pressure and duration of sustained lung inflation (SLI) in the delivery room (DR). We aimed to evaluate the appropriate pressure and duration needed for SLI in preterm infants with respiratory distress syndrome. METHODS: We prospectively randomized 100 preterm (<32 weeks) infants to receive either conventional therapy of continuous positive airway pressure (CPAP) at 5 cm H2O, or four groups of CPAP plus a single maneuver of SLI at four regimens based on administered pressures and durations; P20D20 (Pressure of 20 cm H2O for a duration of 20 seconds), P20D10 (20 cm H2O for 10 seconds), P15D20 (15 cm H2O for 20 seconds), and P15D10 (15 cm H2O for 10 seconds) using a T-piece ventilator. The primary outcome was the need for endotracheal intubation (ETT) in the DR. Broncho-alveolar lavage (BAL) was obtained from intubated infants for interleukin-10 (IL-10) assessment. RESULTS: SLI decreased the need for ETT in the DR (21% versus 55%, p < 0.01) compared to conventional therapy. ETT requirement was significantly lower in P20D10 (20%), P15D20 (20%), and P15D10 (20%) groups, but not P20D20 (25%) compared to the conventional group (55%, p < 0.05). Group P20D20 had significant higher BAL levels of IL-10 [713.8 (IQR 611-874) versus 535.4 (IQR 480-563) pg/ml, p < 0.05] compared to the conventional group, and to other SLI groups. Pneumothorax was not significantly different among studied groups. CONCLUSION: SLI for a pressure and duration ≥20 cm H2O for 20 seconds is not superior to lower pressures for shorter duration and may be injurious to lungs. Sustained versus intermittent lung inflation for resuscitation of preterm infants: a randomized controlled trial. AIM: To evaluate efficacy and safety of delivery room (DR) sustained lung inflation (SLI) in resuscitation of preterm neonates. METHODS: Randomized Controlled Trial including 112 preterm infants randomized to either SLI (n = 57) using T-piece resuscitator [maximum three inflations with maximum pressure of 30 cmH RESULTS: SLI was associated with significantly higher success rate compared to CBMI [75.4 versus 54.5%; p = 0.017], lower need for DR intubation [5.3% versus 23.6%; (X CONCLUSION: Delivery room SLI is more effective than intermittent bag and mask inflation for improving short-term respiratory outcome in preterm infants, without significant adverse effects. Randomised controlled trial of sustained lung inflation for resuscitation of preterm infants in the delivery room. AIM: To compare the effects of sustained lung inflation (SLI) vs. standard resuscitation on physiologic responses of preterm infants during resuscitation. METHODS: Preterm infants (25-32 weeks gestational age) requiring positive-pressure ventilation or continuous positive airway pressure were randomly assigned to either the SLI group (SLI at 25cmH RESULTS: Eighty-one infants were enrolled (SLI group, 43; Non-SLI group, 38). The use of SLI effectively reduced the oxygen requirement. The mean fraction of inspired oxygen 10min after birth was 0.28 (95% CI, 0.26-0.30) in the SLI group and 0.47 (95% CI, 0.43-0.52) in the Non-SLI group (p<0.001). During the first 5min, infants in the SLI group trended towards a higher HR and SpO CONCLUSION: SLI in infants who require respiratory support appears to be effective in facilitating postnatal transition as determined by HR and SpO Sustained Aeration of Infant Lungs (SAIL) trial: study protocol for a randomized controlled trial. BACKGROUND: Extremely preterm infants require assistance recruiting the lung to establish a functional residual capacity after birth. Sustained inflation (SI) combined with positive end expiratory pressure (PEEP) may be a superior method of aerating the lung compared with intermittent positive pressure ventilation (IPPV) with PEEP in extremely preterm infants. The Sustained Aeration of Infant Lungs (SAIL) trial was designed to study this question. METHODS/DESIGN: This multisite prospective randomized controlled unblinded trial will recruit 600 infants of 23 to 26 weeks gestational age who require respiratory support at birth. Infants in both arms will be treated with PEEP 5 to 7 cm H2O throughout the resuscitation. The study intervention consists of performing an initial SI (20 cm H20 for 15 seconds) followed by a second SI (25 cm H2O for 15 seconds), and then PEEP with or without IPPV, as needed. The control group will be treated with initial IPPV with PEEP. The primary outcome is the combined endpoint of bronchopulmonary dysplasia or death at 36 weeks post-menstrual age. TRIAL REGISTRATION: www.clinicaltrials.gov , Trial identifier NCT02139800 , Registered 13 May 2014. Effect of Sustained Inflations vs Intermittent Positive Pressure Ventilation on Bronchopulmonary Dysplasia or Death Among Extremely Preterm Infants: The SAIL Randomized Clinical Trial. Importance: Preterm infants must establish regular respirations at delivery. Sustained inflations may establish lung volume faster than short inflations. Objective: To determine whether a ventilation strategy including sustained inflations, compared with standard intermittent positive pressure ventilation, reduces bronchopulmonary dysplasia (BPD) or death at 36 weeks' postmenstrual age without harm in extremely preterm infants. Design, Setting, and Participants: Unmasked, randomized clinical trial (August 2014 to September 2017, with follow-up to February 15, 2018) conducted in 18 neonatal intensive care units in 9 countries. Preterm infants 23 to 26 weeks' gestational age requiring resuscitation with inadequate respiratory effort or bradycardia were enrolled. Planned enrollment was 600 infants. The trial was stopped after enrolling 426 infants, following a prespecified review of adverse outcomes. Interventions: The experimental intervention was up to 2 sustained inflations at maximal peak pressure of 25 cm H2O for 15 seconds using a T-piece and mask (n = 215); standard resuscitation was intermittent positive pressure ventilation (n = 211). Main Outcome and Measures: The primary outcome was the rate of BPD or death at 36 weeks' postmenstrual age. There were 27 prespecified secondary efficacy outcomes and 7 safety outcomes, including death at less than 48 hours. Results: Among 460 infants randomized (mean [SD] gestational age, 25.30 [0.97] weeks; 50.2% female), 426 infants (92.6%) completed the trial. In the sustained inflation group, 137 infants (63.7%) died or survived with BPD vs 125 infants (59.2%) in the standard resuscitation group (adjusted risk difference [aRD], 4.7% [95% CI, -3.8% to 13.1%]; P = .29). Death at less than 48 hours of age occurred in 16 infants (7.4%) in the sustained inflation group vs 3 infants (1.4%) in the standard resuscitation group (aRD, 5.6% [95% CI, 2.1% to 9.1%]; P = .002). Blinded adjudication detected an imbalance of rates of early death possibly attributable to resuscitation (sustained inflation: 11/16; standard resuscitation: 1/3). Of 27 secondary efficacy outcomes assessed by 36 weeks' postmenstrual age, 26 showed no significant difference between groups. Conclusions and Relevance: Among extremely preterm infants requiring resuscitation at birth, a ventilation strategy involving 2 sustained inflations, compared with standard intermittent positive pressure ventilation, did not reduce the risk of BPD or death at 36 weeks' postmenstrual age. These findings do not support the use of ventilation with sustained inflations among extremely preterm infants, although early termination of the trial limits definitive conclusions. Trial Registration: clinicaltrials.gov Identifier: NCT02139800. Sustained pressure-controlled inflation or intermittent mandatory ventilation in preterm infants in the delivery room? A randomized, controlled trial on initial respiratory support via nasopharyngeal tube. AIM: To prove the hypothesis that sustained pressure-controlled inflation compared to intermittent mandatory ventilation for lung recruitment via nasopharyngeal tube after delivery is more effective in reducing the rate of endotracheal intubation and mechanical ventilation in very preterm infants. METHODS: The study was designed as a randomized, controlled trial. The setting was the delivery room and neonatal intensive care unit of a university hospital in Germany. Subjects were 61 infants (25.0-28.9 wk of gestation) with signs of respiratory distress immediately after birth. The infants were randomized in the delivery room to two different respiratory interventions: either to sustained pressure-controlled inflation (15 s) or to intermittent mandatory ventilation (rate 60 min(-1)). This respiratory support was given by a nasopharyngeal tube. The inflation pressure or peak inspiratory pressure was increased stepwise (20-25-30 cm H2O) according to the response of heart rate and oxygenation. RESULTS: The main outcome measure was treatment failure, i.e., endotracheal intubation and mechanical ventilation according to given intubation criteria. Treatment failure occurred in 61% (95% CI, sustained pressure-controlled inflation: 42-78) and 70% (95% CI, intermittent mandatory ventilation: 51-85) (p = 0.59). The rates of mortality (3/61), severe intraventricular haemorrhage (5/61) and chronic lung disease (10/58) were not different between groups. CONCLUSION: Sufficient spontaneous breathing within the first 48 h of life without endotracheal intubation and mechanical ventilation was achieved in about 30% with both methods of initial respiratory support. Sustained lung inflation at birth for preterm infants: a randomized clinical trial. BACKGROUND: Studies suggest that giving newly born preterm infants sustained lung inflation (SLI) may decrease their need for mechanical ventilation (MV) and improve their respiratory outcomes. METHODS: We randomly assigned infants born at 25 weeks 0 days to 28 weeks 6 days of gestation to receive SLI (25 cm H2O for 15 seconds) followed by nasal continuous positive airway pressure (nCPAP) or nCPAP alone in the delivery room. SLI and nCPAP were delivered by using a neonatal mask and a T-piece ventilator. The primary end point was the need for MV in the first 72 hours of life. The secondary end points included the need for respiratory supports and survival without bronchopulmonary dysplasia (BPD). RESULTS: A total of 148 infants were enrolled in the SLI group and 143 in the control group. Significantly fewer infants were ventilated in the first 72 hours of life in the SLI group (79 of 148 [53%]) than in the control group (93 of 143 [65%]); unadjusted odds ratio: 0.62 [95% confidence interval: 0.38-0.99]; P = .04). The need for respiratory support and survival without BPD did not differ between the groups. Pneumothorax occurred in 1% (n = 2) of infants in the control group compared with 6% (n = 9) in the SLI group, with an unadjusted odds ratio of 4.57 (95% confidence interval: 0.97-21.50; P = .06). CONCLUSIONS: SLI followed by nCPAP in the delivery room decreased the need for MV in the first 72 hours of life in preterm infants at high risk of respiratory distress syndrome compared with nCPAP alone but did not decrease the need for respiratory support and the occurrence of BPD. Sustained lung inflation in late preterm infants: a randomized controlled trial. OBJECTIVE: To assess the need for respiratory support in late preterm infants treated with sustained lung inflation (SLI) at birth. STUDY DESIGN: In this controlled trial, we randomly assigned infants born at 34(+0) to 36(+6) weeks of gestation to receive SLI (25 cmH2O for 15 s) at birth, followed by continuous positive airway pressure (CPAP) or assistance according to the recommendations of the American Academy of Pediatrics. The primary outcome was the need for any type of respiratory support. The secondary outcomes included neonatal intensive care unit (NICU) admission for respiratory distress and length of stay. The risk ratios (RRs) and 95% confidence intervals (CIs) of the outcomes were calculated for the SLI group in reference to the control group. RESULTS: A total of 185 infants were enrolled: 93 in the SLI group and 92 in the control group. No difference was found in the need for any type of respiratory support between the infants treated with SLI and the control group (10.6 vs 8.7%, RR 1.24, 95% CI 0.51 to 2.99). The NICU admission for respiratory distress and the length of stay did not differ between the groups. CONCLUSION: Providing SLI at birth in late preterm infants does not affect their need for respiratory support. Using exhaled CO IMPORTANCE: A sustained inflation (SI) provided at birth might reduce bronchopulmonary dysplasia (BPD). OBJECTIVE: This study aims to examine whether an SI-guided exhaled carbon dioxide (ECO DESIGN: Randomised controlled trial. Infants were randomly allocated to either SI (SI group) or PPV (PPV group). PARTICIPANTS: Participants of this study include infants between 23 INTERVENTION: Infants randomised into the SI group received an initial SI with a peak inflation pressure (PIP) of 24 cmH PRIMARY OUTCOMES: Reduction in BPD defined as the need for respiratory support or supplemental oxygen at corrected gestational age of 36 weeks. RESULTS: SI (n=76) and PPV (n=86) group had similar rates of BPD (23% vs 33%, p=0.090, not statistically significant). The duration of mechanical ventilation was significantly reduced with SI versus PPV (63 (10-246) hours versus 204 (17-562) hours, respectively (p=0.045)). No short-term harmful effects were identified from two SI lasting up to 40 s (eg, pneumothorax, intraventricular haemorrhage or patent ductus arteriosus). CONCLUSION: Preterm infants <33 weeks gestation receiving SI at birth had lower duration of mechanical ventilation and similar incidence of BPD compared with PPV. Using ECO TRIAL REGISTRATION NUMBER: NCT01739114; Results. Chest compression during sustained inflation versus 3:1 chest compression:ventilation ratio during neonatal cardiopulmonary resuscitation: a randomised feasibility trial. BACKGROUND: Current neonatal resuscitation guidelines recommend 3:1 compression:ventilation (C:V) ratio. Recently, animal studies reported that continuous chest compressions (CC) during a sustained inflation (SI) significantly improved return of spontaneous circulation (ROSC). The approach of CC during SI (CC+SI) has not been examined in the delivery room during neonatal resuscitation. HYPOTHESIS: It is a feasibility study to compare CC+SI versus 3:1 C:V ratio during neonatal resuscitation in the delivery room. We hypothesised that during neonatal resuscitation, CC+SI will reduce the time to ROSC. Our aim was to examine if CC+SI reduces ROSC compared with 3:1 C:V CPR in preterm infants <33 weeks of gestation. STUDY DESIGN: Randomised feasibility trial. METHOD: Once CC was indicated all eligible infants were immediately and randomly allocated to either CC+SI group or 3:1 C:V group. A sequentially numbered, brown, sealed envelope contained a folded card box with the treatment allocation was opened by the clinical team at the start of CC. STUDY INTERVENTIONS: Infants in the CC+SI group received CC at a rate of 90/min during an SI with a duration of 20 s (CC+SI). After 20 s, the SI was interrupted for 1 s and the next SI was started for another 20 s until ROSC. Infants in the '3:1 group' received CC using 3:1 C:V ratio until ROSC. PRIMARY OUTCOME: Overall the mean (SD) time to ROSC was significantly shorter in the CC+SI group with 31 (9) s compared with 138 (72) s in the 3:1 C:V group (p=0.011). CONCLUSION: CC+SI is feasible in the delivery room. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT02083705, pre-results. Do Sustained Lung Inflations during Neonatal Resuscitation Affect Cerebral Blood Volume in Preterm Infants? A Randomized Controlled Pilot Study. BACKGROUND: Sustained lung inflations (SLI) during neonatal resuscitation may promote alveolar recruitment in preterm infants. While most of the studies focus on respiratory outcome, the impact of SLI on the brain hasn't been investigated yet. OBJECTIVE: Do SLI affect cerebral blood volume (CBV) in preterm infants? METHODS: Preterm infants of gestation 28 weeks 0 days to 33 weeks 6 days with requirement for respiratory support (RS) were included in this randomized controlled pilot trial. Within the first 15 minutes after birth near-infrared spectroscopy (NIRS) measurements using 'NIRO-200-NX' (Hamamatsu, Japan) were performed to evaluate changes in CBV and cerebral tissue oxygenation. Two groups were compared based on RS: In SLI group RS was given by applying 1-3 SLI (30 cmH2O for 15 s) continued by respiratory standard care. Control group received respiratory standard care only. RESULTS: 40 infants (20 in each group) with mean gestational age of 32 weeks one day (±2 days) and birth weight of 1707 (±470) g were included. In the control group ΔCBV was significantly decreasing, whereas in SLI group ΔCBV showed similar values during the whole period of 15 minutes. Comparing both groups within the first 15 minutes ΔCBV showed a tendency toward different overall courses (p = 0.051). CONCLUSION: This is the first study demonstrating an impact of SLI on CBV. Further studies are warranted including reconfirmation of the present findings in infants with lower gestational age. Future investigations on SLI should not only focus on respiratory outcome but also on the consequences on the developing brain. TRIAL REGISTRATION: German Clinical Trials Register DRKS00005161 https://drks-neu.uniklinik-freiburg.de/drks_web/setLocale_EN.do. Options: A: SLI significantly reduced mortality in the delivery room and during hospitalisation. B: SLI had no significant impact on mortality in the delivery room or during hospitalisation. C: SLI significantly increased the risk of chronic lung disease and pneumothorax. D: SLI significantly reduced the need for endotracheal intubation and surfactant administration.	B
4,606	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What was the primary objective of the research on psychological interventions for people with hemophilia? Please answer this question based on the information provided below: A pilot randomized control trial to evaluate the feasibility of an Internet-based self-management and transitional care program for youth with haemophilia. Adolescents with haemophilia must assume responsibility for their health and management of their disease. An online self-management program was developed to support adolescents during this transition. To determine the feasibility of the program using a randomized control trial (RCT) design in terms of accrual/attrition rates, willingness to be randomized, compliance with the program/outcome measures and satisfaction. Adolescents, ages 13-18, were enrolled in a pilot RCT (NCT01477437) and randomized to either the intervention (8-week program with telephone coaching) or the control arm (no access to the website, weekly telephone call as attention-strategy). All participants completed pre/post-outcome measures. Twenty-nine teens participated (intervention n = 16, control n = 13). Participants in the intervention arm spent an average of 50 min on the website per week and completed the modules in an average of 14 weeks (SD = 4.9). Attrition was higher in the control group compared to the intervention group (54% vs. 25%). 17/18 (94%) who completed the program also completed the poststudy measures. Teens on the intervention arm showed significant improvement in disease-specific knowledge (P = 0.004), self-efficacy (P = 0.007) and transition preparedness (P = 0.046). There was a statistically significant improvement in knowledge in the intervention group when compared to the control group (P = 0.01). Overall, the teens found the website to be informative, comprehensive and easy to use and were satisfied with the program. This pilot RCT study suggests benefit to the program and indicates an RCT design to be feasible with minor adjustments to the protocol. A pilot randomized control trial to evaluate the feasibility of an Internet-based self-management and transitional care program for youth with haemophilia. Adolescents with haemophilia must assume responsibility for their health and management of their disease. An online self-management program was developed to support adolescents during this transition. To determine the feasibility of the program using a randomized control trial (RCT) design in terms of accrual/attrition rates, willingness to be randomized, compliance with the program/outcome measures and satisfaction. Adolescents, ages 13-18, were enrolled in a pilot RCT (NCT01477437) and randomized to either the intervention (8-week program with telephone coaching) or the control arm (no access to the website, weekly telephone call as attention-strategy). All participants completed pre/post-outcome measures. Twenty-nine teens participated (intervention n = 16, control n = 13). Participants in the intervention arm spent an average of 50 min on the website per week and completed the modules in an average of 14 weeks (SD = 4.9). Attrition was higher in the control group compared to the intervention group (54% vs. 25%). 17/18 (94%) who completed the program also completed the poststudy measures. Teens on the intervention arm showed significant improvement in disease-specific knowledge (P = 0.004), self-efficacy (P = 0.007) and transition preparedness (P = 0.046). There was a statistically significant improvement in knowledge in the intervention group when compared to the control group (P = 0.01). Overall, the teens found the website to be informative, comprehensive and easy to use and were satisfied with the program. This pilot RCT study suggests benefit to the program and indicates an RCT design to be feasible with minor adjustments to the protocol. Randomized trial of a DVD intervention to improve readiness to self-manage joint pain. A DVD (digital video disk) intervention to increase readiness to self-manage joint pain secondary to hemophilia was informed by a 2-phase, motivational-volitional model of readiness to self-manage pain, and featured the personal experiences of individuals with hemophilia. The DVD was evaluated in a randomized controlled trial in which 108 men with hemophilia completed measures of readiness to self-manage pain (Pain Stages of Change Questionnaire) before and 6 months after receiving the DVD plus information booklet (n=57) or just the booklet (n=51). The effect of the DVD was assessed by comparing changes in Pain Stages of Change Questionnaire scores (precontemplation, contemplation, and action/maintenance) between groups. The impact on pain coping, pain acceptance, and health-related quality of life was tested in secondary analyses. Repeated-measures analysis of variance, including all those with complete baseline and follow-up data regardless of use of the intervention, showed a significant, medium-sized, group×time effect on precontemplation, with reductions among the DVD group but not the booklet group. Significant use×time effects showed that benefits in terms of contemplation and action/maintenance were restricted to those who used the interventions at least once. The results show that low-intensity interventions in DVD format can improve the motivational impact of written information, and could be used to help prepare people with chronic pain for more intensive self-management interventions. The findings are consistent with a 2-phase, motivational-volitional model of pain self-management, and provide the first insights to our knowledge of readiness to self-manage pain in hemophilia. Effects of a pain self-management intervention combining written and video elements on health-related quality of life among people with different levels of education. Combining written and video material could increase the impact of health education for people with less education, but more evidence is needed about the impact of combined materials in different formats, especially in the context of chronic pain self-management. This study tested the impact of combining written information about self-managing chronic joint pain, which used language at a high reading level, with a DVD containing narrative video material presented directly by patients, using language at a lower reading level. Physical and mental health-related quality of life (36-Item Short Form Health Survey) was measured among 107 men with hemophilia before and 6 months after being randomly assigned to receive an information booklet alone or the booklet plus the DVD. Analysis of covariance was used to compare health outcomes between randomized groups at follow-up, using the baseline measures as covariates, with stratified analyses for groups with different levels of education. The DVD significantly improved mental health-related quality of life among those with only high school education. Video material could therefore supplement written information to increase its impact on groups with less education, and combined interventions of this type could help to achieve health benefits for disadvantaged groups who are most in need of intervention. Auto-hypnosis in haemophilia. A pilot study to determine the use of adjunctive trance therapy in the treatment of haemophiliacs has been carried out. Over a period of forty months, twenty randomly selected males were assigned to a control and an experimental group. All received due haematologic care. The ten patients in the experimental group utilized medical hypnosis as well, in group suggestive sessions to train and sustain them, but primarily in self-induced trance states. Results were compared at intervals on the basis of the amount of transfused blood and blood products. This provided an objective measure of the efficacy of trance therapy. Statistical analysis of the data confirmed the clinical observation of a greater improvement among patients in the experimental group. Progressive versus self-control relaxation to reduce spontaneous bleeding in hemophiliacs. Motivated by previous reports of relaxation successes with hemophiliacs, we sought to isolate the value of relaxation strategies. The effects of progressive and self-control relaxation on spontaneous bleeding and collateral symptoms were tested with seven hemophiliacs in a combined multiple-baseline partial-crossover design. Following 6 or 12 weeks of training in either or both relaxation methods, there was no strong evidence that the treatment affected bleeding or perceived pain in these subjects. These disappointing results were obtained despite within-session physiological evidence of relaxation induction and self- and spouse reports of faithful relaxation practice. The present results failed to replicate previous findings, cast doubt on the stress theory of spontaneous bleeding, and recommend further research to clarify the role of psychological interventions for hemophiliacs. E-learning improves knowledge and practical skills in haemophilia patients on home treatment: a randomized controlled trial. Home treatment of haemophilia is currently the standard of care for patients with severe haemophilia. Home treatment increases the responsibility of the patients for their own treatment and care. Therefore, it is of utmost importance to attain a high level of knowledge and practical skills. The aim of our study was to investigate whether or not an educational e-learning program improves knowledge and skills of adult patients with haemophilia on home treatment. Participants treated at the Haemophilia Treatment Center of the Erasmus University Medical Centre completed a questionnaire to test their knowledge of haemophilia, treatment of bleedings and of complications of treatment and were observed during the intravenous injection of clotting factor concentrate, using a standardized scoring list. Afterwards they were randomized to follow an e-learning program or no intervention (control group). After 1 month they completed the same questionnaire again and practical skills were scored once more. At baseline, haemophilia patients (n = 30) scored 24 of 48 questions in the questionnaire correctly. Seventy-five per cent of the items on the practical skills scoring list were performed correctly. One month later, the e-learning group (n = 16; 36; 18-45) showed a higher level of theoretical knowledge compared to the control group (n = 14; 26; 19-32; P < 0.001). Also practical skills were significantly better in the group that followed the e-learning program compared to the control group (respectively P = 0.002). Self-efficacy of 90% vs. 80% the patients with haemophilia was high in all patients. Our study shows that in haemophilia patients with haemophilia, who are on home treatment, knowledge of haemophilia treatment and complications as well as practical skills can be improved by an educational e-learning program. A pilot randomized control trial to evaluate the feasibility of an Internet-based self-management and transitional care program for youth with haemophilia. Adolescents with haemophilia must assume responsibility for their health and management of their disease. An online self-management program was developed to support adolescents during this transition. To determine the feasibility of the program using a randomized control trial (RCT) design in terms of accrual/attrition rates, willingness to be randomized, compliance with the program/outcome measures and satisfaction. Adolescents, ages 13-18, were enrolled in a pilot RCT (NCT01477437) and randomized to either the intervention (8-week program with telephone coaching) or the control arm (no access to the website, weekly telephone call as attention-strategy). All participants completed pre/post-outcome measures. Twenty-nine teens participated (intervention n = 16, control n = 13). Participants in the intervention arm spent an average of 50 min on the website per week and completed the modules in an average of 14 weeks (SD = 4.9). Attrition was higher in the control group compared to the intervention group (54% vs. 25%). 17/18 (94%) who completed the program also completed the poststudy measures. Teens on the intervention arm showed significant improvement in disease-specific knowledge (P = 0.004), self-efficacy (P = 0.007) and transition preparedness (P = 0.046). There was a statistically significant improvement in knowledge in the intervention group when compared to the control group (P = 0.01). Overall, the teens found the website to be informative, comprehensive and easy to use and were satisfied with the program. This pilot RCT study suggests benefit to the program and indicates an RCT design to be feasible with minor adjustments to the protocol. E-learning improves knowledge and practical skills in haemophilia patients on home treatment: a randomized controlled trial. Home treatment of haemophilia is currently the standard of care for patients with severe haemophilia. Home treatment increases the responsibility of the patients for their own treatment and care. Therefore, it is of utmost importance to attain a high level of knowledge and practical skills. The aim of our study was to investigate whether or not an educational e-learning program improves knowledge and skills of adult patients with haemophilia on home treatment. Participants treated at the Haemophilia Treatment Center of the Erasmus University Medical Centre completed a questionnaire to test their knowledge of haemophilia, treatment of bleedings and of complications of treatment and were observed during the intravenous injection of clotting factor concentrate, using a standardized scoring list. Afterwards they were randomized to follow an e-learning program or no intervention (control group). After 1 month they completed the same questionnaire again and practical skills were scored once more. At baseline, haemophilia patients (n = 30) scored 24 of 48 questions in the questionnaire correctly. Seventy-five per cent of the items on the practical skills scoring list were performed correctly. One month later, the e-learning group (n = 16; 36; 18-45) showed a higher level of theoretical knowledge compared to the control group (n = 14; 26; 19-32; P < 0.001). Also practical skills were significantly better in the group that followed the e-learning program compared to the control group (respectively P = 0.002). Self-efficacy of 90% vs. 80% the patients with haemophilia was high in all patients. Our study shows that in haemophilia patients with haemophilia, who are on home treatment, knowledge of haemophilia treatment and complications as well as practical skills can be improved by an educational e-learning program. The effects of a comprehensive self-hypnosis training program on the use of factor VIII in severe hemophilia. Options: A: To evaluate the effectiveness of psychological therapies in improving the ability of people with hemophilia to cope with their chronic condition. B: To determine the cost-effectiveness of psychological interventions for people with hemophilia. C: To compare the physical health outcomes of different psychological therapies for people with hemophilia. D: To assess the impact of psychological interventions on the frequency of bleeding episodes in people with hemophilia.	A
4,607	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What conclusions can be drawn about the efficacy and safety of different glucocorticoid replacement regimens for treating congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency in children and adults? Please answer this question based on the information provided below: One-year clinical evaluation of single morning dose prednisolone therapy for 21-hydroxylase deficiency. Replacement schedules with hydrocortisone (HC) to treat 21OHD are generally unsatisfactory and partially successful regarding growth. Noncompliance is common since its short half-life requires TID administration. Even multiple daily HC doses do not reproduce cortisol chronobiology and may disturb hypothalamic-mediated rhythms. Because synthetic glucocorticoids could improve clinical control, we evaluated the possible benefits of a one-year treatment period with a single morning oral dose of prednisolone (PD) phosphate in 44 patients with 21OHD randomized to two sex and age-matched groups: one (n=23) receiving PD (2.4-3.5 mg/m2 BSA) and the other (n=21) TID HC (10-15 mg/m2 BSA). After one year, bone maturation ratio was kept stable in the PD group (from 1.20 to 1.14), whereas a slight increase was seen in the HC group (from 1.21 to 1.29). Growth velocity (SDS) was preserved in the PD group (from 1.2 to 1.2 in all; 0.79 to 1.13 in pre-pubertals), whereas a slight increase occurred in the pre-pubertal HC-treated patients (from 1.1 to 1.9); height SDS for BA increased significantly in the PD group. Thus, patients with 21OHD treated for one year with a single morning dose of PD appear to achieve a better clinical and hormonal control than those on TID HC, permitting a reduction of the replacement dose. The current PD schedule used by our group (1.5-3 mg/m2 BSA/day) suggests a higher HC:PD bioequivalence ratio of 6-8:1. Control of childhood congenital adrenal hyperplasia and sleep activity and quality with morning or evening glucocorticoid therapy. CONTEXT: Traditionally, hydrocortisone (HC) replacement therapy in congenital adrenal hyperplasia (CAH) is given by three daily doses, albeit not necessarily of equal quantity. Although a higher dose in the morning better imitates the physiological diurnal variation, a late-night higher dose was suggested to better suppress early morning hypothalamic-pituitary-adrenal axis peak activity. Yet, increased night cortisol has been claimed to be associated with sleep disturbances and insomnia. OBJECTIVE: Our objective was to evaluate evening vs. morning high-HC dose with respect to disease control, sleep pattern, and daytime activity in children with CAH. DESIGN: An open-label, cross-over, randomized trial of 15 children with classical CAH was performed. Patients were randomized to receive 50% of the daily HC in the morning or evening for 2 wk; the other two doses included 25% of the daily dose each. OUTCOME MEASURES: Disease control was assessed by 0800-h 17-hydroxyprogesterone, testosterone, androstenedione, and dehydroepiandrosterone sulfate on the last day of each treatment schedule. Sleep and daytime activity were assessed by a 7-d actigraph. RESULTS: Basal morning androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, and testosterone levels during the high-morning and high-evening HC treatment schedules were comparable. There were no significant differences in sleep or daytime activity. CONCLUSIONS: With respect to disease control, sleep quality and daytime activity were not affected by treatment schedules. We recommend the high-morning dose schedule in replacement therapy of children with CAH. Differential effects of hydrocortisone, prednisone, and dexamethasone on hormonal and pharmacokinetic profiles: a pilot study in children with congenital adrenal hyperplasia. BACKGROUND: Little is known about the comparative effects of different glucocorticoids on the adrenal and growth hormone (GH) axes in children with congenital adrenal hyperplasia (CAH). We sought to compare the effects of hydrocortisone (HC), prednisone (PDN), and dexamethasone (DEX) in children with classic CAH and to investigate a potential role of pharmacogenetics. METHODS: Subjects were randomly assigned to three sequential 6-week courses of HC, PDN, and DEX, each followed by evaluation of adrenal hormones, IGF-1, GH, and body mass index (BMI). Single nucleotide polymorphism (SNP) analysis of genes in the glucocorticoid pathway was also performed. RESULTS: Nine prepubertal subjects aged 8.1 ± 2.3 years completed the study. Mean ACTH, androstenedione, and 17-hydroxyprogesterone (17-OHP) values were lower following the DEX arm of the study than after subjects received HC (p ≤ 0.016) or PDN (p ≤ 0.002). 17-OHP was also lower after HC than PDN (p < 0.001). There was no difference in IGF-1, GH, or change in BMI. SNP analysis revealed significant associations between hormone concentrations, pharmacokinetic parameters, and variants in several glucocorticoid pathway genes (ABCB1, NR3C1, IP013, GLCCI1). CONCLUSIONS: DEX resulted in marked adrenal suppression suggesting that its potency relative to hydrocortisone and prednisone was underestimated. SNPs conferred significant differences in responses between subjects. Although preliminary, these pilot data suggest that incorporating pharmacogenetics has the potential to eventually lead to targeted therapy in children with CAH. Randomised controlled trial of growth effect of hydrocortisone in congenital adrenal hyperplasia. The influence of 15 or 25 mg/m2 of daily oral hydrocortisone with fludrocortisone 0.1 mg/day on growth and laboratory findings was evaluated in a prospective randomised crossover trial over 12 months in 26 children with 21-hydroxylase deficiency. Nine non-salt losers had fludrocortisone stopped for a further six month period. Height velocity was significantly decreased during treatment with 25 mg/m2 as compared with 15 mg/m2. This was the most sensitive indicator of corticosteroid treatment excess. A dose dependent effect upon plasma concentrations of 17-hydroxyprogesterone, testosterone, and androstenedione was found but increased values were still detected in more than half of the determinations made during the 25 mg/m2 period. Height velocity and 17-hydroxyprogesterone concentrations were positively correlated. Growth hormone response to clonidine stimulation and insulin-like growth factor-1 concentrations were both within reference values and there was no difference between treatment periods. Withdrawal of fludrocortisone did not result in any difference for the non-salt losers. It was concluded that 25 mg/m2 of hydrocortisone depressed growth in children with congenital adrenal hyperplasia, and that full suppression, or even normalisation, of plasma concentrations of 17-hydroxyprogesterone and androgens should not be considered a treatment goal, but instead an indication of corticosteroid treatment excess. Effect of hydrocortisone dose schedule on adrenal steroid secretion in congenital adrenal hyperplasia. Effect of hydrocortisone dose schedule on adrenal steroid secretion in congenital adrenal hyperplasia. To explore the potential effect of dose schedule on the adrenal suppressive action of hydrocortisone in congenital adrenal hyperplasia, eight patients (six with 21-hydroxylase deficiency and two with 11-hydroxylase deficiency) were given five different dose schedules. Two of the schedules used single daily doses (morning or evening), two twice daily doses (two-thirds dose in the morning or evening), one and three equal doses at morning, noon, and night. Each dose schedule used the same total daily hydrocortisone dose (12.5 mg/m2/day), which is within the normal range of hydrocortisone production rate. Each schedule was given for 4 to 6 weeks. The different dose schedules caused the predicted alterations in the temporal pattern of adrenal steroid levels, with the greatest apparent suppression during the 2 to 4 hours after each dose. None of the schedules, however, caused significant differences in the mean 24-hour plasma concentration of 17-hydroxyprogesterone (21-hydroxylase deficiency) or 11-deoxycortisol (11-hydroxylase deficiency) or in the 24-hour urine pregnanetriol or 17-ketosteroid concentrations, either in the six patients undertreated at the dose of 12.5 mg/m2/day or in the two patients adequately treated. Nocturnal administration of all or a part of the daily dose did not improve adrenal suppression. These observations suggest that treatment of congenital adrenal hyperplasia with a once-a-day hydrocortisone dose schedule may be as effective as conventional multiple-dose schedules. Until this hypothesis has been tested by more extended clinical studies, however, we do not recommend a once-a-day schedule. Regardless of the dose schedule, the total daily hydrocortisone dose must be adjusted to achieve a normal rate of growth and bone age advancement. Options: A: There is strong evidence supporting the superiority of hydrocortisone over prednisolone and dexamethasone in managing CAH. B: The evidence is insufficient to determine the most effective glucocorticoid replacement regimen for CAH due to limited and heterogeneous trials. C: Prednisolone is clearly more effective than hydrocortisone and dexamethasone in normalizing androgen levels and improving growth outcomes. D: Dexamethasone is the preferred treatment due to its superior efficacy in preventing adrenal crises and improving quality of life.	B
4,608	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What were the findings regarding the effectiveness and safety of lamotrigine as an add-on treatment for drug-resistant focal epilepsy? Please answer this question based on the information provided below: A comparison of pregabalin, lamotrigine, and placebo as adjunctive therapy in patients with refractory partial-onset seizures. PURPOSE: This study assessed the comparative efficacy of pregabalin for refractory partial seizures. METHODS: Four-hundred and thirty-four patients with partial seizures were randomized to pregabalin, lamotrigine, or placebo as adjunctive therapy for 17 weeks of double-blind treatment. In phase I (11 weeks), pregabalin was titrated over 1 week and lamotrigine over 5 weeks to fixed dosages of 300mg/day for both. In phase II (6 weeks), patients not yet seizure-free were increased to pregabalin 600mg/day or lamotrigine 400mg/day. RESULTS: During phase I, there was a nonsignificant trend toward a greater reduction in seizures with pregabalin versus placebo and lamotrigine. Across the 17 weeks of treatment, pregabalin showed a median percentage reduction from baseline in seizure frequency of -20.0% (p=.001) versus placebo, and -9.7% (p=.080) versus lamotrigine. The responder rate (> or =50% reduction in seizure frequency) for pregabalin exceeded that of placebo (36% vs 21%; p=.007) and lamotrigine (36% vs 24%; p=.04). Adverse events were consistent with the known safety profiles of pregabalin and lamotrigine. DISCUSSION: Pregabalin was demonstrated to be noninferior to lamotrigine in the treatment of refractory partial seizures. Overall conclusions were complicated by an unusually large and heterogeneous placebo response. Double-blind crossover trial of lamotrigine (Lamictal) as add-on therapy in intractable epilepsy. A double-blind, placebo-controlled trial is reported of lamotrigine as add-on treatment in therapy-resistant epilepsy. A within-patients serial design was used, with two 3-month treatment periods and an intervening 6-week washout/crossover period. An unblinded investigator adjusted lamotrigine dosage to achieve a plasma concentration within a previously predicted therapeutic range. All patients had therapy-resistant partial seizures, some in combination with other seizure types and were without serious neurological or intellectual deficit. Of 34 patients recruited only one was withdrawn because of an adverse experience (maculo-papular rash) probably related to the experimental drug and 30 completed the trial. The other 3 withdrawals were due to default during baseline, dispensing error and cholecystectomy. There was a modest statistically significant reduction in total and partial seizures on lamotrigine compared to placebo treatment. There was no difference in adverse experiences or abnormal biochemical or haematological findings between the lamotrigine and placebo periods. The plasma concentrations of concomitantly administered antiepileptic drugs were not affected by lamotrigine treatment. It is concluded that lamotrigine shows promise as an antiepileptic drug with low toxicity. Controlled trial of lamotrigine (Lamictal) for treatment-resistant partial seizures. The antiepileptic effect of lamotrigine (Lamictal) was assessed in a double-blind, placebo-controlled, crossover trial in 56 adult patients with refractory partial seizures. Lamotrigine or placebo was added to the patients' existing antiepileptic drugs (AEDs). The dose of lamotrigine varied from 75 to 400 mg daily. Thirty-eight patients completed the trial and 7 withdrew because of adverse experiences. There was a statistically significant reduction in seizure counts on lamotrigine compared with placebo for total seizures (30.3% reduction, 95% CI 8.4%, 47.0%), complex partial seizures (29.2% reduction, 95% CI 3.8%, 47.9%) and secondary generalised seizures (37.9%, CI 18.9%, 52.4%). The analysis of total seizure days showed a similar significant reduction during lamotrigine treatment for the same seizure categories. There was no statistically significant difference in reporting of adverse events between lamotrigine and placebo except for dizziness which was reported more frequently on lamotrigine than on placebo. There were no differences in abnormal haematological or biochemical findings between lamotrigine and placebo, and lamotrigine had no effect on plasma concentrations of concomitant AEDs. A placebo-controlled trial of lamotrigine add-on therapy for partial seizures in children. Lamictal Pediatric Partial Seizure Study Group. OBJECTIVE: To compare the safety and efficacy of add-on lamotrigine and placebo in the treatment of children and adolescents with partial seizures. BACKGROUND: Add-on and monotherapy lamotrigine is safe and effective in adults with partial seizures, and reports of preliminary uncontrolled trials suggest similar benefits in children. METHODS: We studied 201 children with diagnoses of partial seizures of any subtype currently receiving stable conventional regimens of antiepileptic therapy at 40 study sites in the United States and France. After a baseline observation period (to confirm that more than four seizures occurred in each of two consecutive 4-week periods), patients were randomized to add-on lamotrigine or placebo therapy. A 6-week dose-escalation period was followed by a 12-week maintenance period. RESULTS: Compared with placebo, lamotrigine significantly reduced the frequency of all partial seizures and the frequency of secondarily generalized partial seizures in these treatment-resistant patients. The most commonly reported adverse events in the lamotrigine-treated patients were vomiting, somnolence, and infection; the frequency of these and other adverse events was similar to that in the placebo-treated group, with the exception of ataxia, dizziness, tremor, and nausea, which were more frequent in the lamotrigine-treated group. The frequency of withdrawals for adverse events was similar between groups. Two patients were hospitalized for skin rash, which resolved after discontinuation of lamotrigine therapy. CONCLUSIONS: Lamotrigine was effective for the adjunctive treatment of partial seizures in children and demonstrated an acceptable safety profile. Controlled trial of lamotrigine (Lamictal) for refractory partial seizures. The antiepileptic effect of lamotrigine (LTG) was assessed in a double-blind, placebo-controlled crossover trial in 24 adult patients with refractory partial seizures. LTG or placebo was added to existing antiepileptic drugs (AEDs). The dose of LTG varied from 75 to 400 mg daily. Three patients did not complete the trial. One was withdrawn from the trial with ataxia, tiredness, dyspnea, and diplopia while receiving LTG and died 18 days later of invasive carcinoma involving the liver. A second patient was withdrawn during baseline for contravening admission criteria, and a third received LTG in error during both treatment periods. Twenty-one patients (12 men and 9 women) completed the trial. An analysis of seizure counts in the 12-week treatment period with LTG showed a statistically significant reduction in seizures as compared with placebo for total seizures (p less than 0.002), partial seizures (p less than 0.002), and secondarily generalized seizures (p less than 0.05). The analysis of total seizure days showed a significant reduction during LTG treatment (p less than 0.002). There were no statistically significant changes in plasma concentrations of phenytoin (PHT), carbamazepine (CBZ), primidone (PRM), or phenobarbital (PB) between the two treatment periods. The most common adverse events reported during the trial were diplopia, drowsiness, tiredness, ataxia, and headache, but although these were more frequent during LTG treatment, the differences from placebo were not statistically significant. No hematological or biochemical changes were noted. A randomised double-blind placebo-controlled crossover add-on trial of lamotrigine in patients with treatment-resistant partial seizures. Efficacy and safety of lamotrigine (LTG) as add-on therapy was assessed in a randomised double-blind placebo-controlled trial of this drug in 23 adult patients with refractory partial seizures. Fifteen patients showed an improvement on LTG treatment, with a greater than 50% decrease in total seizure count in 7 patients. Fourteen patients experienced fewer simple and complex partial seizures, with 8 patients benefitting by more than a 50% decrease in seizure frequency. The drug was well tolerated over the 2 month treatment period. The plasma concentration of concomitant antiepileptic drugs remained unchanged. No haematological or chemical abnormalities were noted. Placebo-controlled study of the efficacy and safety of lamotrigine in patients with partial seizures. U.S. Lamotrigine Protocol 0.5 Clinical Trial Group. We evaluated the efficacy and safety of lamotrigine (300 and 500 mg/day) as add-on therapy in a multicenter, randomized, double-blind, parallel-group, placebo-controlled study of 216 patients with refractory partial seizures. During 6 months of treatment, median seizure frequency decreased by 8% with placebo, 20% with 300 mg lamotrigine, and 36% with 500 mg lamotrigine. Seizure frequency decreased by > or = 50% in one-third of the 500-mg group and one-fifth of the 300-mg group. Reductions in seizure frequency and seizure days were statistically significant, compared with placebo, for the 500-mg group but not the 300-mg group. Most adverse events were minor and resolved over time. Nine percent of patients on lamotrigine withdrew because of adverse experiences. Lamotrigine plasma concentrations appeared to be a linear function of dose, and the drug did not affect plasma concentrations of concomitant antiepileptic drugs. Lamotrigine was safe, effective, and well tolerated as add-on therapy for refractory partial seizures. Lamotrigine therapy for partial seizures: a multicenter, placebo-controlled, double-blind, cross-over trial. The efficacy and safety of lamotrigine (LTG), a new antiepileptic drug (AED), were evaluated in a multicenter, randomized, double-blind, placebo-controlled, cross-over study of 98 patients with refractory partial seizures. Each treatment period lasted 14 weeks. Most patients were titrated to a LTG maintenance dose of 400 mg/day. Seizure frequency with LTG decreased by > or = 50%, as compared with placebo, in one fifth of patients. Overall median seizure frequency decreased by 25% with LTG as compared with placebo (p < 0.001). With LTG, the number of seizure days decreased by 18% as compared with placebo (p < 0.01), and investigator global evaluation of overall patient clinical status favored LTG by 2:1 (p = 0.013). Plasma LTG concentrations appeared to be linearly related to dosage. LTG had no clinically important effects on the plasma concentrations of concomitant AEDs. Adverse experiences were generally minor and most frequently were CNS-related (e.g., ataxia, dizziness, diplopia, headache). Most were transient and resolved without discontinuing treatment. Five patients withdrew as a result of adverse experiences while receiving LTG, including 3 patients with rash. One placebo patient was also withdrawn because of rash. The addition of twice-daily LTG to an existing AED regimen was safe, effective, and well tolerated in these medically refractory partial seizure patients. Lamotrigine extended-release as adjunctive therapy for partial seizures. OBJECTIVE: To evaluate the efficacy and tolerability of once-daily adjunctive lamotrigine extended-release (XR) for partial seizures in epilepsy. METHODS: Patients more than 12 years old diagnosed with epilepsy with partial seizures and taking one to two baseline antiepileptic drugs were randomized to adjunctive once-daily lamotrigine XR or placebo in a double-blind, parallel-group trial. The study comprised a baseline phase, a 7-week double-blind escalation phase, and a 12-week double-blind maintenance phase during which doses of study medication and concomitant antiepileptic drugs were maintained. RESULTS: Of the 243 randomized patients, 239 (118 lamotrigine XR, 121 placebo) entered the escalation phase and received study medication. Lamotrigine XR was more effective than placebo with respect to median percent reduction from baseline in weekly partial seizure frequency (primary endpoint-entire 19-week treatment phase: 46.6% vs 24.5%, p = 0.0001 [corrected] via Wilcoxon test; escalation phase: 29.8% vs 15.6%, p = 0.027; maintenance phase: 58.4% vs 26.8%, p [corrected] < 0.0001). The percentage of patients with >or=50% reduction in partial seizure frequency (44.0% vs 20.8%, p = 0.0002) [corrected] and time to >or=50% reduction in partial seizure frequency (p = 0.0001) [corrected] also favored lamotrigine XR over placebo. A similar pattern of results was observed for secondarily generalized seizures. The most common adverse events were headache (lamotrigine XR 16%, placebo 18%) [corrected] and dizziness (lamotrigine XR 19%, [corrected] placebo 5%). Differences between lamotrigine XR and placebo on health outcomes measures were not significant. CONCLUSIONS: Once-daily adjunctive lamotrigine extended-release compared with placebo effectively reduced partial seizure frequency and was well tolerated in this double-blind study. Results support the clinical utility of this new once-daily formulation. Adjunctive lamotrigine for partial seizures in patients aged 1 to 24 months. OBJECTIVE: This randomized, double-blind, placebo-controlled trial was conducted to assess the efficacy and tolerability of adjunctive lamotrigine for the treatment of partial seizures in infants aged 1 to 24 months. METHODS: The study used a responder-enriched design in which all patients received adjunctive lamotrigine during an open-label phase (n = 177; maximum maintenance dose 5.1 mg/kg/day for those on non-enzyme-inducing antiepileptic drugs [AEDs] or valproate and 15.6 mg/kg/day for those on enzyme-inducing AEDs). Patients meeting response criteria were randomly assigned to double-blind treatment for up to 8 weeks with continued lamotrigine (n = 19) or to withdrawal from lamotrigine (placebo; n = 19) while background AEDs were maintained. RESULTS: The proportion of treatment failures (patients who met escape criteria or withdrew before completing the double-blind phase) was lower with lamotrigine (58%) than with placebo (84%). This finding was not significant in the primary analysis (two-sided chi(2) test [primary endpoint]). A post hoc sensitivity analysis of the primary endpoint was also performed (p = 0.045 by one-sided, mid-p corrected Fisher exact test). The median time to meet escape criteria was longer with lamotrigine (42 days) than with placebo (22 days) (p = 0.059). During the last 28 days of the open-label phase, 53% of the patients had a >or=50% reduction in frequency of partial seizures with lamotrigine. Additional reduction in partial seizure frequency was observed during the double-blind phase compared with the last 4 weeks of the open-label phase among those randomly assigned to lamotrigine (32% with a >or=25% reduction) but not those randomly assigned to placebo (5% with a >or=25% reduction). Lamotrigine was well tolerated, with an adverse event profile comparable to that observed in older pediatric patients. CONCLUSION: Lamotrigine was well tolerated, and the data indicate that it may be efficacious in the treatment of partial seizures in infants aged 1 to 24 months. Double-blind, placebo controlled, crossover study of lamotrigine in treatment resistant partial seizures. The results of a multicentre, randomised, double-blind, placebo controlled, crossover trial of lamotrigine as add-on therapy in patients with partial seizures poorly controlled by established antiepileptic drugs (AEDs) are presented. The study consisted of two 12 week treatment periods each followed by a four week washout period. During the lamotrigine treatment phase, patients received 150 mg or 300 mg daily dose depending on their concomitant AEDs to achieve concentrations in the range 1-3 mg/L. Forty one patients were entered at four centres and all patients entered completed the study. There was a highly significant (p < 0.001) decrease in total seizure counts on lamotrigine compared with placebo. Overall, 22% of patients experienced at least a 50% reduction in the total numbers of all seizures types on lamotrigine, compared with none on placebo. When the total numbers of partial seizures (simple and complex partial) were analysed there was also a significant (p < 0.05) reduction in seizure counts on lamotrigine compared with placebo. When total numbers of secondarily generalised seizures were compared the trend for a reduction in this seizure type did not achieve significance (0.05 < p < 0.1). Concomitant AED plasma concentrations were virtually unchanged. It is concluded that lamotrigine is an effective AED in the treatment of therapy-resistant partial seizures. Outcomes of add-on treatment with lamotrigine in partial epilepsy. The need for new antiepileptic drugs (AEDs) and more sensitive methods of assessing their efficacy is well recognized. This study was designed to evaluate the efficacy and safety of lamotrigine (LTG), a potential new AED and to develop and test new outcome measures. A health-related quality of life (HRQL) model was developed which contains previously validated measures of anxiety, depression, happiness, overall mood, self-esteem, and mastery and a specifically designed seizure severity scale with patient- and caregiver-based components. This HRQL model was used in a randomized, placebo-controlled, double-blind, cross-over study of LTG in 81 patients with refractory partial seizures. Seizure frequency was the primary measure and seizure severity and the HRQL were secondary measures of efficacy. The reduction in seizure frequency with LTG, relative to placebo, was 29.7% [95% confidence interval (CI) 17.8%, 39.9%] for total seizure count, 33.4% (95% CI 14.8%, 47.9%) for complex partial seizures (CPS) and 20.3% (95% CI 0.3%, 36.2%) for secondarily generalized tonic-clonic seizures (GTCS). However, although 41 patients elected to continue with LTG, only 11 experienced at least 50% reduction in total seizures, indicating that other factors influenced their decision. The score with LTG, relative to placebo, was significantly lower for the ictal (p = 0.017) and caregivers (p = 0.035) subscales of the seizure severity scale and significantly higher for happiness (p = 0.003) and mastery (p = 0.003). Simple correlation and multiple-regression analyses indicate that the effects on seizure frequency, seizure severity, and psychological variables appear to be independent of each other. This study indicates that LTG is effective in reducing seizure frequency and has additional favorable effects on seizure severity, mood, and perceived internal control. Some of the scales used indicate the potential of secondary measures of efficacy to enhance the sensitivity of trials of new AEDs. Options: A: Lamotrigine was found to be ineffective in reducing seizure frequency and had no significant adverse effects. B: Lamotrigine significantly reduced seizure frequency and was associated with several adverse effects such as ataxia, dizziness, diplopia, and nausea. C: Lamotrigine had no significant impact on seizure frequency but was associated with improved cognition and quality of life. D: Lamotrigine significantly reduced seizure frequency and had no adverse effects.	B
4,609	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What are the effects of convective radiofrequency water vapour thermal therapy on lower urinary tract symptoms and quality of life in men with benign prostatic hyperplasia, compared to a sham procedure? Please answer this question based on the information provided below: Erectile and Ejaculatory Function Preserved With Convective Water Vapor Energy Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: Randomized Controlled Study. INTRODUCTION: Most surgical treatments for male lower urinary tract symptoms and benign prostatic hyperplasia affect erectile and ejaculatory functions negatively, leading to patient dissatisfaction. AIM: To determine whether water vapor thermal therapy, when conducted in a randomized controlled trial, would significantly improve lower urinary tract symptoms secondary to benign prostatic hyperplasia and urinary flow rate while preserving erectile and ejaculatory functions. METHODS: Men at least 50 years old with International Prostate Symptom Scores of at least 13, a peak flow rate of at least 5 to no higher than 15 mL/s, and prostate volume of 30 to 80 cm(3) were randomized 2:1 between Rezūm System thermal therapy and control. Thermal water vapor (103°C) was injected into lateral and median lobes as required for treatment of benign prostatic hyperplasia. The control procedure entailed rigid cystoscopy with simulated active treatment sounds. MAIN OUTCOME MEASURES: Blinded group (active = 136, control = 61) comparison occurred at 3 months and the active arm was followed to 12 months for International Prostate Symptom Score, peak flow rate, and sexual function using the International Index of Erectile Function and the Male Sexual Health Questionnaire for Ejaculatory Function. The minimal clinically important difference in erectile function perceived by subjects as beneficial was determined for each erectile function severity category. Subjects not sexually active were censored from sexual function analysis. RESULTS: No treatment- or device-related de novo erectile dysfunction occurred after thermal therapy. International Index of Erectile Function and Male Sexual Health Questionnaire for Ejaculatory Function scores were not different from the control group at 3 months or from baseline at 1 year. Ejaculatory bother score improved 31% over baseline (P = .0011). Also, 32% of subjects achieved minimal clinically important differences in erectile function scores at 3 months, and 27% at 1 year, including those with moderate to severe erectile dysfunction. International Prostate Symptom Score and peak flow rate were significantly superior to controls at 3 months and throughout 1 year (P < .0001). CONCLUSION: Convective water vapor thermal therapy provides sustainable improvements for 12 months to lower urinary tract symptoms and urinary flow while preserving erectile and ejaculatory functions. Minimally Invasive Prostate Convective Water Vapor Energy Ablation: A Multicenter, Randomized, Controlled Study for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia. PURPOSE: This report reveals the results of a multicenter, randomized, controlled study using transurethral prostate convective water vapor thermal energy to treat lower urinary tract symptoms associated with benign prostatic hyperplasia. MATERIALS AND METHODS: Men 50 years old or older with an International Prostate Symptom Score of 13 or greater, maximum flow rate of 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 between thermal therapy with the Rezūm® System and control. Thermal water vapor was injected into the transition zone and median lobe as needed. The control procedure was rigid cystoscopy with simulated active treatment sounds. The primary end point compared International Prostate Symptom Score reduction at 3 months. Treatment subjects were followed for 12 months. RESULTS: There were 197 men randomized (active 136, control 61). Thermal therapy and control International Prostate Symptom Score was reduced by 11.2 ± 7.6 and 4.3 ± 6.9 respectively (p <0.0001). Treatment subject baseline International Prostate Symptom Score of 22 decreased at 2 weeks (18.6, p=0.0006) and by 50% or greater at 3, 6 and 12 months, p <0.0001. The peak flow rate increased by 6.2 ml per second at 3 months and was sustained throughout 12 months (p <0.0001). No de novo erectile dysfunction was reported. Adverse events were mild to moderate and resolved quickly. CONCLUSIONS: Convective water vapor thermal therapy provides rapid and durable improvements in benign prostatic hyperplasia symptoms and preserves erectile and ejaculatory function. Treatment can be delivered in an office or hospital setting using oral pain medication and is applicable to all prostate zones including the median lobe. Three-Year Outcomes of the Prospective, Randomized Controlled Rezūm System Study: Convective Radiofrequency Thermal Therapy for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia. OBJECTIVE: To report 3-year outcomes of a prospective, multicenter, randomized, blinded control trial after treatment with convective radiofrequency (RF) water vapor thermal therapy for moderate to severe lower urinary tract symptoms due to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Fifteen centers enrolled and randomized 197 men ≥50 years old with International Prostate Symptom Score (IPSS) ≥13, maximum flow rate (Qmax) ≤15 mL/s, and prostate volume 30 to 80 cc to thermal therapy with Rezūm System or control (2:1). Rigid cystoscopy with simulated active treatment sound effects served as the control procedure. Convective RF thermal energy was delivered into obstructive prostate tissue including the median lobe as needed. After randomized comparison at 3 months, thermal therapy subjects were followed annually for 3 years. RESULTS: Convective RF thermal therapy yielded IPSS improvement of 160% compared with control subjects at 3 months (P <.0001). Maximal symptom relief of at least 50% improvement in IPSS, quality of life, Qmax, and BPH Impact Index remained durable throughout 3 years (P <.0001). Subjects with a treated median lobe had similar responses. No late-related adverse events occurred, and no de novo erectile dysfunction was reported. The surgical retreatment rate was 4.4% over 3 years. CONCLUSION: The minimally invasive convective RF thermal therapy is an office or ambulatory outpatient procedure with minimal transient perioperative side effects. It provides early effective and durable relief of BPH symptoms with preservation of sexual function in subjects followed up for 3 years and is applicable to treatment of the median lobe and hyperplastic central zone tissue. Rezūm Water Vapor Thermal Therapy for Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia: 4-Year Results From Randomized Controlled Study. OBJECTIVE: To report 4-year outcomes of the randomized controlled trial of water vapor thermal therapy for treatment of moderate to severe lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: Total 188 subjects; 135 men ≥50years old, International Prostate Symptom Score ≥ 13, maximum flow rate (Qmax) ≤15 mL/s and prostate volume 30 to 80 cc treated with Rezūm System thermal therapy were followed 4 years; subset of 53 men who requalified for crossover from control to active treatment were followed 3years. RESULTS: Lower urinary tract symptoms were significantly improved within ≤3 months after thermal therapy and remained consistently durable (International Prostate Symptom Score 47%, quality of life 43%, Qmax 50%, Benign Prostatic Hyperplasia Impact Index 52%) throughout 4years (P <.0001); outcomes were similarly sustained in crossover subjects at 3years. Surgical retreatment rate was 4.4% over 4years. No disturbances in sexual function were reported. CONCLUSION: The minimally invasive thermal therapy provides effective symptom relief and improved quality of life that remains durable for over 4years. It is applicable to all prostate zones with procedures performed under local anesthesia in an office setting. Convective Thermal Therapy: Durable 2-Year Results of Randomized Controlled and Prospective Crossover Studies for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia. PURPOSE: We report 2-year outcomes of a multicenter randomized controlled trial plus 1-year results of a crossover trial after treatment with convective radiofrequency water vapor thermal energy for lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 men at least 50 years old with I-PSS (International Prostate Symptom Score) 13 or greater, maximum flow rate 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 to thermal therapy with the Rezūm® System or a control group. Rigid cystoscopy with simulated active treatment sounds served as the control procedure. After unblinding at 3 months control subjects could requalify for crossover study. Convectively delivered radiofrequency thermal energy was delivered into obstructive prostate tissue, including the median lobe as needed. The primary efficacy end point was a change in severity of symptom scores. RESULTS: Convective radiofrequency thermal therapy improved urinary symptoms significantly over controls at 3 months and provided a sustained 51% reduction from baseline at 24 months (p <0.0001). This produced a 5 and 8-point or greater score decrease in 84% and 74% of subjects, respectively, at 24 months. Crossover subject symptoms, flow rate and quality of life measures were markedly improved after thermal therapy compared to after the control procedure (p = 0.024 to <0.0001). No de novo erectile dysfunction was reported. CONCLUSIONS: Convective radiofrequency water vapor thermal therapy is a minimally invasive office or outpatient procedure that provides early effective symptom relief that remains durable for 2 years and is applicable to the median lobe. Convective Thermal Therapy: Durable 2-Year Results of Randomized Controlled and Prospective Crossover Studies for Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia. PURPOSE: We report 2-year outcomes of a multicenter randomized controlled trial plus 1-year results of a crossover trial after treatment with convective radiofrequency water vapor thermal energy for lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 197 men at least 50 years old with I-PSS (International Prostate Symptom Score) 13 or greater, maximum flow rate 15 ml per second or less and prostate size 30 to 80 cc were randomized 2:1 to thermal therapy with the Rezūm® System or a control group. Rigid cystoscopy with simulated active treatment sounds served as the control procedure. After unblinding at 3 months control subjects could requalify for crossover study. Convectively delivered radiofrequency thermal energy was delivered into obstructive prostate tissue, including the median lobe as needed. The primary efficacy end point was a change in severity of symptom scores. RESULTS: Convective radiofrequency thermal therapy improved urinary symptoms significantly over controls at 3 months and provided a sustained 51% reduction from baseline at 24 months (p <0.0001). This produced a 5 and 8-point or greater score decrease in 84% and 74% of subjects, respectively, at 24 months. Crossover subject symptoms, flow rate and quality of life measures were markedly improved after thermal therapy compared to after the control procedure (p = 0.024 to <0.0001). No de novo erectile dysfunction was reported. CONCLUSIONS: Convective radiofrequency water vapor thermal therapy is a minimally invasive office or outpatient procedure that provides early effective symptom relief that remains durable for 2 years and is applicable to the median lobe. Options: A: It may improve urologic symptom scores and likely improves quality of life. B: It has no significant effect on urologic symptom scores or quality of life. C: It worsens urologic symptom scores and decreases quality of life. D: It has a significant effect on urologic symptom scores but no effect on quality of life.	A
4,610	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the impact of maternal and perinatal death audits and reviews, when included as part of a complex intervention, on maternal and perinatal mortality and quality of care in different settings? Please answer this question based on the information provided below: Quality of care, risk management, and technology in obstetrics to reduce hospital-based maternal mortality in Senegal and Mali (QUARITE): a cluster-randomised trial. BACKGROUND: Maternal mortality is higher in west Africa than in most industrialised countries, so the development and validation of effective interventions is essential. We did a trial to assess the effect of a multifaceted intervention to promote maternity death reviews and onsite training in emergency obstetric care in referral hospitals with high maternal mortality rates in Senegal and Mali. METHODS: We did a pragmatic cluster-randomised controlled trial, with hospitals as the units of randomisation and patients as the unit of analysis. 46 public first-level and second-level referral hospitals with more than 800 deliveries a year were enrolled, stratified by country and hospital type, and randomly assigned to either the intervention group (n=23) or the control group with no external intervention (n=23). All women who delivered in each of the participating facilities during the baseline and post-intervention periods were included. The intervention, implemented over a period of 2 years at the hospital level, consisted of an initial interactive workshop and quarterly educational clinically-oriented and evidence-based outreach visits focused on maternal death reviews and best practices implementation. The primary outcome was reduction of risk of hospital-based mortality. Analysis was by intention-to-treat and relied on the generalised estimating equations extension of the logistic regression model to account for clustering of women within hospitals. This study is registered with ClinicalTrials.gov, number ISRCTN46950658. FINDINGS: 191,167 patients who delivered in the participating hospitals were analysed (95,931 in the intervention groups and 95,236 in the control groups). Overall, mortality reduction in intervention hospitals was significantly higher than in control hospitals (odds ratio [OR] 0·85, 95% CI 0·73-0·98, p=0·0299), but this effect was limited to capital and district hospitals, which mainly acted as first-level referral hospitals in this trial. There was no effect in second-level referral (regional) hospitals outside the capitals (OR 1·02, 95% CI 0·79-1·31, p=0·89). No hospitals were lost to follow-up. Concrete actions were implemented comprehensively to improve quality of care in intervention hospitals. INTERPRETATION: Regular visits by a trained external facilitator and onsite training can provide health-care professionals with the knowledge and confidence to make quality improvement suggestions during audit sessions. Maternal death reviews, combined with best practices implementation, are effective in reducing hospital-based mortality in first-level referral hospitals. Further studies are needed to determine whether the benefits of the intervention are generalisable to second-level referral hospitals. FUNDING: Canadian Institutes of Health Research. Effect of a facility-based multifaceted intervention on the quality of obstetrical care: a cluster randomized controlled trial in Mali and Senegal. BACKGROUND: Maternal mortality in referral hospitals in Mali and Senegal surpasses 1% of obstetrical admissions. Poor quality obstetrical care contributes to high maternal mortality; however, poor care is often linked to insufficient hospital resources. One promising method to improve obstetrical care is maternal death review. With a cluster randomized trial, we assessed whether an intervention, based on maternal death review, could improve obstetrical quality of care. METHODS: The trial began with a pre-intervention year (2007), followed by two years of intervention activities and a post-intervention year. We measured obstetrical quality of care in the post-intervention year using a criterion-based clinical audit (CBCA). We collected data from 32 of the 46 trial hospitals (16 in each trial arm) and included 658 patients admitted to the maternity unit with a trial of labour. The CBCA questionnaire measured 5 dimensions of care- patient history, clinical examination, laboratory examination, delivery care and postpartum monitoring. We used adjusted mixed models to evaluate differences in CBCA scores by trial arms and examined how levels of hospital human and material resources affect quality of care differences associated with the intervention. RESULTS: For all women, the mean percentage of care criteria met was 66.3 (SD 13.5). There were significantly greater mean CBCA scores in women treated at intervention hospitals (68.2) compared to control hospitals (64.5). After adjustment, women treated at intervention sites had 5 points' greater scores than those at control sites. This difference was mostly attributable to greater clinical examination and post-partum monitoring scores. The association between the intervention and quality of care was the same, irrespective of the level of resources available to a hospital; however, as resources increased, so did quality of care scores in both arms of the trial. Effect of maternal death reviews and training on maternal mortality among cesarean delivery: post-hoc analysis of a cluster-randomized controlled trial. OBJECTIVES: To explore the differential effect of a multifaceted intervention on hospital-based maternal mortality between patients with cesarean and vaginal delivery in low-resource settings. STUDY DESIGN: We reanalyzed the data from a major cluster-randomized controlled trial, QUARITE (Quality of care, Risk management and technology in obstetrics). These subgroup analyses were not pre-specified and were treated as exploratory. The intervention consisted of an initial interactive workshop and quarterly educational clinically oriented and evidence-based outreach visits focused on maternal death reviews (MDR) and best practices implementation. The trial originally recruited 191,167 patients who delivered in each of the 46 participating hospitals in Mali and Senegal, between 2007 and 2011. The primary endpoint was hospital-based maternal mortality. Subgroup-specific Odds Ratios (ORs) of maternal mortality were computed and tested for differential intervention effect using generalized linear mixed model between two subgroups (cesarean: 40,975; and vaginal delivery: 150,192). RESULTS: The test for homogeneity of intervention effects on hospital-based maternal mortality among the two delivery mode subgroups was statistically significant (p-value: 0.0201). Compared to the control, the adjusted OR of maternal mortality was 0.71 (95% CI: 0.58-0.82, p=0.0034) among women with cesarean delivery. The intervention had no significant effect among women with vaginal delivery (adjusted OR 0.87, 95% CI 0.69-1.11, p=0.6213). This differential effect was particularly marked for district hospitals. CONCLUSION: Maternal deaths reviews and on-site training on emergency obstetric care may be more effective in reducing maternal mortality among high-risk women who need a cesarean section than among low-risk women with vaginal delivery. Multifaceted intervention to improve obstetric practices: The OPERA cluster-randomized controlled trial. OBJECTIVE: Suboptimal care contributes to perinatal morbidity and mortality. We investigated the effects of a multifaceted program designed to improve obstetric practices and outcomes. STUDY DESIGN: A cluster-randomized trial was conducted from October 2008 to November 2010 in 95 French maternity units randomized either to receive an information intervention about published guidelines or left to apply them freely. The intervention combined an outreach visit with a morbidity/mortality conference (MMC) to review perinatal morbidity/mortality cases. Within the intervention group, the units were randomized to have MMCs with or without clinical psychologists. The primary outcome was the rate of suboptimal care among perinatal morbidity/mortality cases. The secondary outcomes included the rate of suboptimal care among cases of morbidity, the rate of suboptimal care among cases of mortality, the rate of avoidable morbidity and/or mortality cases, and the incidence of, morbidity and/or mortality. A mixed logistic regression model with random intercept was used to quantify the effect of the intervention on the main outcome. RESULTS: The study reviewed 2459 cases of morbidity or mortality among 165,353 births. The rate of suboptimal care among morbidity plus mortality cases was not significantly lower in the intervention than in the control group (8.1% vs. 10.6%, OR [95% CI]: 0.75 [0.50-1.12], p=0.15. However, the cases of suboptimal care among morbidity cases were significantly lower in the intervention group (7.6% vs. 11.5%, 0.62 [0.40-0.94], p=0.02); the incidence of perinatal morbidity was also lower (7.0 vs. 8.1‰, p=0.01). No differences were found between psychologist-backed and the other units. CONCLUSIONS: The intervention reduced the rate of suboptimal care mainly in morbidity cases and the incidence of morbidity but did not succeed in improving morbidity plus mortality combined. More clear-cut results regarding mortality require a longer study period and the inclusion of structures that intervene before and after the delivery room. (ClinicalTrials.gov ID: NCT02584166). Options: A: Maternal death audits and reviews, as part of a complex intervention, probably reduce inpatient maternal mortality and slightly improve quality of care in low-income country district hospitals. B: Perinatal death audits and reviews, as part of a complex intervention, probably reduce overall perinatal mortality in high-income settings where mortality was already very low. C: Maternal and perinatal death audits and reviews, when conducted in isolation, are sufficient to achieve significant reductions in mortality. D: There is no evidence to suggest that maternal and perinatal death audits and reviews have any impact on mortality or quality of care.	A
4,611	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What are the potential effects of breathing exercises on adults with asthma? Please answer this question based on the information provided below: Assessment of significance of BACKGROUND: Asthma is a chronic inflammatory respiratory disease characterized by periodic attacks of wheezing, shortness of breath and a tight feeling in the chest. The current study is based on the effect of MATERIALS AND METHODS: A total of 300 participants of mild-to-moderate persistent asthma (FEV RESULTS: In "the CONCLUSION: "The Yoga training improves quality of life in women with asthma. OBJECTIVES: Individuals with asthma frequently suffer with a decrease in quality of life. Yoga has been shown to improve autonomic function in the healthy population and has been used as an alternative therapy to help improve symptoms associated with various diseases. PURPOSE: The purpose of this study was to assess whether 10 weeks of yoga training can improve quality of life and heart rate variability (HRV) in patients with asthma. DESIGN: Nineteen (19) females were randomly assigned to a yoga group or a control group for a 10-week intervention while still following guidelines established by their physician. All subjects answered the St. George's Respiratory Questionnaire (SGRQ) to assess quality of life and performed an isometric handgrip exercise test to assess HRV. RESULTS: Based on the SGRQ, significant improvements (45%, p < 0.05) in quality of life were observed with the yoga training, while no changes were found in the control group. Resting hemodynamic measures improved significantly in the yoga group compared to the control group (p < 0.05). The yoga group decreased parasympathetic modulation (HFnu [normalized units]) pre- to postintervention (0.45 ± 0.60 to 0.35 ± 0.06 nu, p<0.05, respectively) in response to the isometric forearm exercise (IFE), whereas the control group did not change. Additionally, the yoga group increased sympathetic (LFnu) (pre 0.47 ± 0.07 to post 0.60 ± 0.07 nu, p < 0.05) and sympathovagal modulation (logLF/HF) (pre 4.61 ± 0.39 to post 5.31 ± 0.44, p < 0.05, respectively) during IFE with no change in the control group. CONCLUSIONS: Yoga training improved quality of life in women with mild-to-moderate asthma and resulted in decreased parasympathetic and increased sympathetic modulation in response to an IFE. [Long-term effects of breathing exercises and yoga in patients with bronchial asthma]. To compare the effects of breathing exercises (BE) or Yoga (Y) on the course of bronchial asthma we studied 36 subjects with a mild disease. The patients were randomly divided into 3 groups. 2 of them participated in a 3 weeks training program of BE or Y while the third group rested without any additional treatment (control group, C). At the end of the training period the patients were asked to practise BE or Y on their own. Drug therapy and lung function parameters before and after a beta 2-agonist metered dose inhaler (albuterol, ALB) were recorded prior to the training program and in 4 weeks intervals for 4 months thereafter. The response to the beta 2-agonist was documented continuously in 28 patients. The mental state of the patients was elucidated by questionnaires.--Prior to the study a significant effect of inhaled ALB on the FEV1 was shown without any significant between group differences. Both, BE and Y, caused a significant amelioration of the mental state but only the BE induced a significant improvement of lung function parameters compared to the individual baseline values. The FEV1 increased significantly by 356.3 +/- 146.2 ml (p < 0.05) and the VC by 225.0 +/- 65.5 ml (p < 0.01). These long-term changes were not significantly different from the actual response to ALB. BE decreased the RV significantly by 306.3 +/- 111.6 ml (p < 0.05), an effect significantly higher compared to the beta 2-agonist (p < 0.01). BE in combination with ALB caused an additive effect.(ABSTRACT TRUNCATED AT 250 WORDS) Deep diaphragmatic breathing: rehabilitation exercises for the asthmatic patient. A new diaphragmatic breathing technique practiced without the aid of a physical corset is outlined, and the findings from a study of its application in the respiratory rehabilitation of asthmatic patients are presented. Sixty-seven asthmatic adults randomly assigned to either deep diaphragmatic breathing training, physical exercise training, or a waiting list control group participated in a 16-week program. Deep diaphragmatic training resulted in significant reductions in medication use and in the intensity of asthmatic symptoms. Importantly, a nearly 300% increase in time spent in physical activities also resulted from deep diaphragmatic training. A follow-up at two months found many patients had returned to earlier medication levels and sedentary habits. A strengthened musculature can replace the need for a physical aid in this respiratory habilitation; adherence to its use may require individually-tailored encouragement. The effect of physiotherapy-based breathing retraining on asthma control. BACKGROUND: The mechanism of the breathing retraining effect on asthma control is not adequately based on evidence. OBJECTIVE: The present study was designed to evaluate the effect of physiotherapy-based breathing retraining on asthma control and on asthma physiological indices across time. STUDY DESIGN: A 6-month controlled study was conducted. Adult patients with stable, mild to moderate asthma (n = 40), under the same specialist's care, were randomized either to be trained as one group receiving 12 individual breathing retraining sessions (n = 20), or to have usual asthma care (n = 20). The main outcome was the Asthma Control Test score, with secondary outcomes the end-tidal carbon dioxide, respiratory rate, spirometry, and the scores of Nijmegen Hyperventilation Questionnaire, Medical Research Council scale, and SF-36v2 quality-of-life questionnaire. RESULTS: The 2 × 4 ANOVA showed significant interaction between intervention and time in asthma control (F = 9.03, p < .001, η(2) = 0.19), end-tidal carbon dioxide (p < .001), respiratory rate (p < .001), symptoms of hypocapnia (p = .001), FEV1% predicted (p = .022), and breathlessness disability (p = .023). The 2 × 4 MANOVA showed significant interaction between intervention and time, with respect to the two components of the SF-36v2 (p < .001). CONCLUSION: Breathing retraining resulted in improvement not only in asthma control but in physiological indices across time as well. Further studies are needed to confirm the benefits of this training in order to help patients with stable asthma achieve the control of their disease. Integrated breathing and relaxation training (the Papworth method) for adults with asthma in primary care: a randomised controlled trial. BACKGROUND: An integrated breathing and relaxation technique known as the Papworth method has been implemented by physiotherapists since the 1960s for patients with asthma and dysfunctional breathing, but no controlled trials have been reported. This study evaluated the effectiveness of the Papworth method in a randomised controlled trial. METHODS: Eighty-five patients (36 men) were individually randomised to the control group (n = 46) or to the intervention group receiving five sessions of treatment by the Papworth method (n = 39). Both groups received usual medical care. Assessments were undertaken at baseline, post-treatment (6 months after baseline) and at 12 months. The primary outcome measure was the St George's Respiratory Symptoms Questionnaire (SGRQ). Secondary outcome measures included the Hospital Anxiety and Depression Scale (HADS), the Nijmegen dysfunctional breathing questionnaire and objective measures of respiratory function. RESULTS: Post-treatment and 12 month data were available for 78 and 72 patients, respectively. At the post-treatment assessment the mean (SD) score on the SGRQ Symptom subscale was 21.8 (18.1) in the intervention group and 32.8 (20.1) in the control group (p = 0.001 for the difference). At the 12 month follow-up the corresponding figures were 24.9 (17.9) and 33.5 (15.9) (p = 0.007 for the difference). SGRQ Total scores and HADS and Nijmegen scores were similarly significantly lower in the intervention group than in the control group. The groups did not differ significantly following the treatment on objective measures of respiratory function except for relaxed breathing rate. CONCLUSIONS: The Papworth method appears to ameliorate respiratory symptoms, dysfunctional breathing and adverse mood compared with usual care. Further controlled trials are warranted to confirm this finding, assess the effect in other patient groups and determine whether there is some effect on objective measures of respiratory function. Yoga for bronchial asthma: a controlled study. Fifty three patients with asthma underwent training for two weeks in an integrated set of yoga exercises, including breathing exercises, suryanamaskar, yogasana (physical postures), pranayama (breath slowing techniques), dhyana (meditation), and a devotional session, and were told to practise these exercises for 65 minutes daily. They were then compared with a control group of 53 patients with asthma matched for age, sex, and type and severity of asthma, who continued to take their usual drugs. There was a significantly greater improvement in the group who practised yoga in the weekly number of attacks of asthma, scores for drug treatment, and peak flow rate. This study shows the efficacy of yoga in the long term management of bronchial asthma, but the physiological basis for this beneficial effect needs to be examined in more detail. Comparison of the effects of Buteyko and pranayama breathing techniques on quality of life in patients with asthma - a randomized controlled trial. OBJECTIVE: To compare two breathing exercises (Buteyko and pranayama) with a control group in patients with asthma. DESIGN: Randomized controlled trial. SUBJECTS: One hundred and twenty subjects were randomized to three groups through block randomization. Subjects with an Asthma Quality of Life Questionnaire score <5.5 participated in the study. SETTING: Outpatient pulmonary medicine department. INTERVENTIONS: Subjects in the Buteyko and pranayama groups were trained for 3-5 days and instructed to practise the exercises for 15 minutes twice daily, and for three months duration. The control group underwent routine pharmacological management during the study period. OUTCOME MEASURES: Asthma Quality of Life Questionnaire, Asthma Control Questionnaire and pulmonary function test. RESULTS: The baseline characteristics were similar in all three groups. Post intervention, the Buteyko group showed better trends of improvement (mean (95% confidence interval), P-value) in total Asthma Quality of Life Questionnaire score than the pranayama (0.47 (-0.008-0.95), P = 0.056) and control groups (0.97 (0.48-1.46), P = 0.0001). In comparison between the pranayama and control groups, pranayama showed significant improvement (0.50 (0.01-0.98), P = 0.042) in total Asthma Quality of Life Questionnaire score. CONCLUSION: The Buteyko group showed better trends of improvement in quality of life and asthma control than the group performing the pranayama breathing exercise. Effect of yoga practices on pulmonary function tests including transfer factor of lung for carbon monoxide (TLCO) in asthma patients. Prana is the energy, when the self-energizing force embraces the body with extension and expansion and control, it is pranayama. It may affect the milieu at the bronchioles and the alveoli particularly at the alveolo-capillary membrane to facilitate diffusion and transport of gases. It may also increase oxygenation at tissue level. Aim of our study is to compare pulmonary functions and diffusion capacity in patients of bronchial asthma before and after yogic intervention of 2 months. Sixty stable asthmatic-patients were randomized into two groups i.e group 1 (Yoga training group) and group 2 (control group). Each group included thirty patients. Lung functions were recorded on all patients at baseline, and then after two months. Group 1 subjects showed a statistically significant improvement (P<0.001) in Transfer factor of the lung for carbon monoxide (TLCO), forced vital capacity (FVC), forced expiratory volume in 1st sec (FEV1), peak expiratory flow rate (PEFR), maximum voluntary ventilation (MVV) and slow vital capacity (SVC) after yoga practice. Quality of life also increased significantly. It was concluded that pranayama & yoga breathing and stretching postures are used to increase respiratory stamina, relax the chest muscles, expand the lungs, raise energy levels, and calm the body. Assessment of the quality of life in patients with bronchial asthma, before and after yoga: a randomised trial. Yoga which is used as an adjunct treatment for bronchial asthma is gaining popularity throughout the world. The objective of this study was to assess the effect of yoga on quality of life in patients with bronchial asthma. 120 non-smoking male and female patients of asthma in the age group of 17-50 years were randomized into two groups i.e. Group A (Yoga group) and Group B (control group). All patients remained on their prescribed medication, but Group A patients practiced yoga breathing exercises for 8 weeks. Asthma Quality of Life Questionnaire (AQLQ) and diary record was used to assess quality of life, number and severity of asthmatic attacks, and the dosage of the medication required at baseline and after 8 weeks. Group A subjects showed a statistically significant improvement in "symptoms", "activities" and "environmental" domains of AQLQ at 8 weeks (p<0.01) and significant reduction in daily number and severity of attacks, and the dosage of medication required at 4 and 8 weeks (p<0.01) compared to the baseline. Yoga breathing exercises used adjunctively with standard pharmacological treatment significantly improved quality of life in patients with bronchial asthma. A study of the effect of yoga training on pulmonary functions in patients with bronchial asthma. The role of yoga breathing exercises, as an adjunct treatment for bronchial asthma is well recognized. One hundred twenty patients of asthma were randomized into two groups i.e Group A (yoga training group) and Group B (control group). Each group included sixty patients. Pulmonary function tests were performed on all the patients at baseline, after 4 weeks and then after 8 weeks. Majority of the subjects in the two groups had mild disease (34 patients in Group A and 32 in Group B). Group A subjects showed a statistically significant increasing trend (P < 0.01) in % predicted peak expiratory flow rate (PEFR), forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), forced mid expiratory flow in 0.25-0.75 seconds (FEF25-75) and FEV1/FVC% ratio at 4 weeks and 8 weeks as compared to Group B. Thus, yoga breathing exercises used adjunctively with standard pharmacological treatment significantly improves pulmonary functions in patients with bronchial asthma. Breathing retraining for dysfunctional breathing in asthma: a randomised controlled trial. BACKGROUND: Functional breathing disorders may complicate asthma and impair quality of life. This study aimed to determine the effectiveness of physiotherapy based breathing retraining for patients treated for asthma in the community who have symptoms suggestive of dysfunctional breathing. METHODS: 33 adult patients aged 17-65 with diagnosed and currently treated asthma and Nijmegen questionnaire scores > or =23 were recruited to a randomised controlled trial comparing short physiotherapy breathing retraining and an asthma nurse education control. The main outcome measures were asthma specific health status (Asthma Quality of Life questionnaire) and Nijmegen questionnaire scores RESULTS: Of the 33 who entered the study, data were available on 31 after 1 month and 28 at 6 months. The median (interquartile range) changes in overall asthma quality of life score at 1 month were 0.6 (0.05-1.12) and 0.09 (-0.25-0.26) for the breathing retraining and education groups, respectively (p=0.018), 0.42 (0.11-1.17) and 0.09 (-0.58-0.5) for the symptoms domain (p=0.042), 0.52 (0.09-1.25) and 0 (-0.45-0.45) for the activities domain (p=0.007), and 0.50 (0-1.50) and -0.25 (-0.75-0.75) for the environment domain (p=0.018). Only the change in the activities domain remained significant at 6 months (0.83 (-0.10-1.71) and -0.05 (-0.74-0.34), p=0.018), although trends to improvement were seen in the overall score (p=0.065), the symptoms domain (p=0.059), and the environment domain (p=0.065). There was a correlation between changes in quality of life scores and Nijmegen questionnaire scores at 1 month and at 6 months. The number needed to treat to produce a clinically important improvement in health status was 1.96 and 3.57 at 1 and 6 months. CONCLUSION: Over half the patients treated for asthma in the community who have symptoms suggestive of dysfunctional breathing show a clinically relevant improvement in quality of life following a brief physiotherapy intervention. This improvement is maintained in over 25% 6 months after the intervention. Breathing exercises for asthma: a randomised controlled trial. BACKGROUND: The effect of breathing modification techniques on asthma symptoms and objective disease control is uncertain. METHODS: A prospective, parallel group, single-blind, randomised controlled trial comparing breathing training with asthma education (to control for non-specific effects of clinician attention) was performed. Subjects with asthma with impaired health status managed in primary care were randomised to receive three sessions of either physiotherapist-supervised breathing training (n = 94) or asthma nurse-delivered asthma education (n = 89). The main outcome was Asthma Quality of Life Questionnaire (AQLQ) score, with secondary outcomes including spirometry, bronchial hyper-responsiveness, exhaled nitric oxide, induced sputum eosinophil count and Asthma Control Questionnaire (ACQ), Hospital Anxiety and Depression (HAD) and hyperventilation (Nijmegen) questionnaire scores. RESULTS: One month after the intervention there were similar improvements in AQLQ scores from baseline in both groups but at 6 months there was a significant between-group difference favouring breathing training (0.38 units, 95% CI 0.08 to 0.68). At the 6-month assessment there were significant between-group differences favouring breathing training in HAD anxiety (1.1, 95% CI 0.2 to 1.9), HAD depression (0.8, 95% CI 0.1 to 1.4) and Nijmegen (3.2, 95% CI 1.0 to 5.4) scores, with trends to improved ACQ (0.2, 95% CI 0.0 to 0.4). No significant between-group differences were seen at 1 month. Breathing training was not associated with significant changes in airways physiology, inflammation or hyper-responsiveness. CONCLUSION: Breathing training resulted in improvements in asthma-specific health status and other patient-centred measures but not in asthma pathophysiology. Such exercises may help patients whose quality of life is impaired by asthma, but they are unlikely to reduce the need for anti-inflammatory medication. Physiotherapy breathing retraining for asthma: a randomised controlled trial. BACKGROUND: Despite effective pharmacotherapy, asthma continues to impair quality of life for most patients. Non-pharmacological approaches, including breathing retraining, are therefore of great interest to patients. However, clinicians rarely advocate breathing retraining and access to this intervention is restricted for most patients due to the limited availability of suitable physiotherapists and poor integration of breathing retraining into standard care. We aimed to assess the effectiveness of a digital self-guided breathing retraining intervention. METHODS: In this randomised controlled trial, we recruited patients from 34 general practices in the UK. Eligibility criteria for patients with asthma were broad, comprising a physician diagnosis of asthma, age of 16-70 years, receipt of at least one anti-asthma medication in the previous year, and impaired asthma-related quality of life (Asthma Quality of Life Questionnaire [AQLQ] score of <5·5). We developed a self-guided intervention, which was delivered as a DVD plus a printed booklet (DVDB). Participants were randomly assigned to receive either the DVDB intervention, three face-to-face breathing retraining sessions, or standard care, in a 2:1:2 ratio, for 12 months. Randomisation was achieved using the Southampton Clinical Trials Unit telephone randomisation service by use of random number generators. The primary outcome was the AQLQ score in the intention-to-treat population at 12 months. The trial was powered to show equivalence between the two active intervention groups, and superiority of both intervention groups over usual care. Secondary outcomes included patient-reported and physiological measures of asthma control, patient acceptability, and health-care costs. This trial was registered with International Standard Randomised Controlled Trial Number registry, number ISRCTN88318003. FINDINGS: Between Nov 5, 2012 and Jan 28, 2014, invitations to participate in the study were sent to 15 203 patients with general practitioner-diagnosed asthma, of whom 655 were recruited into the study. AQLQ scores at 12 months were significantly higher in the DVDB group (mean 5·40, SD 1·14) than in the usual care group (5·12, SD 1·17; adjusted mean difference 0·28, 95% CI 0·11 to 0·44), and in the face-to-face group (5·33, SD 1·06) than in the usual care group (adjusted mean difference 0·24, 95% CI 0·04 to 0·44); AQLQ scores were similar between the DVDB group and the face-to-face group (0·04, 95% CI -0·16 to 0·24). There were no significant differences between the randomisation groups in FEV1 or fraction of exhaled nitric oxide. 744 adverse events occurred in 272 patients: 101 (39%) of 261 patients in the DVDB group, 55 (42%) of 132 patients in the face-to-face group, and 132 (50%) of 262 in the usual care group, with patients reporting one or more event. 11 (4%) patients in the DVDB group, four (3%) patients in the face-to-face group, and 20 (8%) patients in the usual care group had a serious adverse event. INTERPRETATION: Breathing retraining programmes improve quality of life in patients with incompletely controlled asthma despite having little effect on lung function or airway inflammation. Such programmes can be delivered conveniently and cost-effectively as a self-guided digital audiovisual programme, so might also reduce health-care costs. FUNDING: UK National Institute of Health Research. A randomised controlled study of the effectiveness of breathing retraining exercises taught by a physiotherapist either by instructional DVD or in face-to-face sessions in the management of asthma in adults. BACKGROUND: Asthma control is suboptimal, resulting in quality of life (QoL) impairment and costs. Breathing retraining exercises have evidence of effectiveness as adjuvant treatment, but are infrequently used. OBJECTIVES: To transfer the contents of a brief (three-session) physiotherapist-delivered breathing retraining programme to a digital versatile disc (DVD) and booklet format; to compare the effectiveness of the self-guided intervention with that of 'face-to-face' physiotherapy and usual care for QoL and other asthma-related outcomes; to perform a health economic assessment of both interventions; and to perform a process evaluation using quantitative and qualitative methods. DESIGN: Parallel-group three-arm randomised controlled trial. SETTING: General practice surgeries in the UK. PARTICIPANTS: In total, 655 adults currently receiving asthma treatment with impaired asthma-related QoL were randomly allocated to the DVD ( INTERVENTIONS: Physiotherapy-based breathing retraining delivered through three 'face-to-face' respiratory physiotherapist sessions or a self-guided programme (DVD plus our theory-based behaviour change booklet) developed by the research team, with a control of usual care. MAIN OUTCOME MEASURES: The primary outcome measure was asthma-specific QoL, measured using the Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes included asthma symptom control [Asthma Control Questionnaire (ACQ)], psychological state [Hospital Anxiety and Depression Scale (HADS)], hyperventilation symptoms (Nijmegen questionnaire), generic QoL [EuroQol-5 Dimensions (EQ-5D)], assessments of airway physiology (spirometry) and inflammation (exhaled nitric oxide) and health resource use and costs. Assessments were carried out at baseline and at 3, 6 and 12 months post randomisation. Patient engagement and experience were also assessed using quantitative and qualitative methods. RESULTS: Primary efficacy analysis was between-group comparison of changes in AQLQ scores from baseline to 12 months in the intention-to-treat population with adjustments for prespecified covariates. Significant improvements occurred in the DVD group compared with the control group [adjusted mean difference 0.28, 95% confidence interval (CI) 0.11 to 0.44; CONCLUSIONS: Only 10% of the potentially eligible population responded to the study invitation. However, breathing retraining exercises improved QoL and reduced health-care costs in adults with asthma whose condition remains uncontrolled despite standard pharmacological therapy, were engaged with well by patients and can be delivered effectively as a self-guided intervention. The intervention should now be transferred to an internet-based platform and implementation studies performed. Interventions for younger patients should be developed and trialled. TRIAL REGISTRATION: Current Controlled Trials ISRCTN88318003. FUNDING: This project was primarily funded by the NIHR Health Technology Assessment programme and will be published in full in Clinical study of yoga techniques in university students with asthma: a controlled study. Adult asthmatics, ranging from 19 to 52 years from an asthma and allergy clinic in a university setting volunteered to participate in the study. The 17 students were randomly divided into yoga (9 subjects) and nonyoga control (8 subjects) groups. The yoga group was taught a set of breathing and relaxation techniques including breath slowing exercises (pranayama), physical postures (yogasanas), and meditation. Yoga techniques were taught at the university health center, three times a week for 16 weeks. All the subjects in both groups maintained daily symptom and medication diaries, collected A.M. and P.M. peak flow readings, and completed weekly questionnaires. Spirometry was performed on each subject every week. Analysis of the data showed that the subjects in the yoga group reported a significant degree of relaxation, positive attitude, and better yoga exercise tolerance. There was also a tendency toward lesser usage of beta adrenergic inhalers. The pulmonary functions did not vary significantly between yoga and control groups. Yoga techniques seem beneficial as an adjunct to the medical management of asthma. The efficacy of a comprehensive lifestyle modification programme based on yoga in the management of bronchial asthma: a randomized controlled trial. BACKGROUND: There is a substantial body of evidence on the efficacy of yoga in the management of bronchial asthma. Many studies have reported, as the effects of yoga on bronchial asthma, significant improvements in pulmonary functions, quality of life and reduction in airway hyper-reactivity, frequency of attacks and medication use. In addition, a few studies have attempted to understand the effects of yoga on exercise-induced bronchoconstriction (EIB) or exercise tolerance capacity. However, none of these studies has investigated any immunological mechanisms by which yoga improves these variables in bronchial asthma. METHODS: The present randomized controlled trial (RCT) was conducted on 57 adult subjects with mild or moderate bronchial asthma who were allocated randomly to either the yoga (intervention) group (n = 29) or the wait-listed control group (n = 28). The control group received only conventional care and the yoga group received an intervention based on yoga, in addition to the conventional care. The intervention consisted of 2-wk supervised training in lifestyle modification and stress management based on yoga followed by closely monitored continuation of the practices at home for 6-wk. The outcome measures were assessed in both the groups at 0 wk (baseline), 2, 4 and 8 wk by using Generalized Linear Model (GLM) repeated measures followed by post-hoc analysis. RESULTS: In the yoga group, there was a steady and progressive improvement in pulmonary function, the change being statistically significant in case of the first second of forced expiratory volume (FEV1) at 8 wk, and peak expiratory flow rate (PEFR) at 2, 4 and 8 wk as compared to the corresponding baseline values. There was a significant reduction in EIB in the yoga group. However, there was no corresponding reduction in the urinary prostaglandin D2 metabolite (11beta prostaglandin F2alpha) levels in response to the exercise challenge. There was also no significant change in serum eosinophilic cationic protein levels during the 8-wk study period in either group. There was a significant improvement in Asthma Quality of Life (AQOL) scores in both groups over the 8-wk study period. But the improvement was achieved earlier and was more complete in the yoga group. The number-needed-to-treat worked out to be 1.82 for the total AQOL score. An improvement in total AQOL score was greater than the minimal important difference and the same outcome was achieved for the sub-domains of the AQOL. The frequency of rescue medication use showed a significant decrease over the study period in both the groups. However, the decrease was achieved relatively earlier and was more marked in the yoga group than in the control group. CONCLUSION: The present RCT has demonstrated that adding the mind-body approach of yoga to the predominantly physical approach of conventional care results in measurable improvement in subjective as well as objective outcomes in bronchial asthma. The trial supports the efficacy of yoga in the management of bronchial asthma. However, the preliminary efforts made towards working out the mechanism of action of the intervention have not thrown much light on how yoga works in bronchial asthma. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00815962. Options: A: Breathing exercises have no significant impact on quality of life, asthma symptoms, hyperventilation symptoms, or lung function. B: Breathing exercises may improve quality of life, reduce hyperventilation symptoms, and have some positive effects on lung function, but the evidence quality ranges from moderate to very low. C: Breathing exercises significantly worsen asthma symptoms and lung function in adults with asthma. D: Breathing exercises are only effective in improving asthma symptoms but have no impact on quality of life or lung function.	B
4,612	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the effectiveness and safety of prophylactic antibiotics in reducing infectious puerperal morbidities in women undergoing operative vaginal deliveries? Please answer this question based on the information provided below: Factors associated with infection after operative vaginal birth-a secondary analysis of a randomized controlled trial of prophylactic antibiotics for the prevention of infection following operative vaginal birth. BACKGROUND: A recent randomized controlled trial of prophylactic antibiotics for the prevention of infection following operative vaginal birth showed that women allocated prophylactic intravenous amoxicillin and clavulanic acid had a significantly lower risk of developing confirmed or suspected infection within 6 weeks after operative vaginal birth (risk ratio [RR], 0.58; 95% confidence interval [CI], 0.49-0.69; P < .001). Some international and national guidelines have subsequently been updated to include prophylactic antibiotics after operative vaginal birth. However, the generalizability of the trial results may be limited in settings where the episiotomy rate is lower (89% of women in the trial had an episiotomy). In addition, there was a high burden of infection in the prophylactic antibiotics group despite the administration of prophylactic antibiotics. It is essential to identify modifiable risk factors for infection after operative vaginal birth, including the timing of antibiotic administration. OBJECTIVE: This study aimed to evaluate if the effectiveness of the prophylactic antibiotic in reducing confirmed or suspected infection was independent of perineal trauma, identify risk factors for infection after operative vaginal birth, and investigate variation in efficacy with the timing of antibiotic administration. STUDY DESIGN: This study was a secondary analysis of 3225 women with primary outcome data from the prophylactic antibiotics for the prevention of infection following operative vaginal birth randomized controlled trial. Women were divided into subgroups according to the perineal trauma experienced (episiotomy and/or perineal tear). The consistency of the prophylactic antibiotics in preventing infection across the subgroups was assessed using log-binomial regression and the likelihood ratio test. Multivariable log-binomial regression was used to investigate factors associated with infection. The multivariable risk factor model was subsequently fitted to the group of women who received amoxicillin and clavulanic acid to investigate the timing of antibiotic administration. RESULTS: Of the 3225 women included in the secondary analysis, 2144 (66.5%) had an episiotomy alone, 726 (22.5%) had an episiotomy and a tear, 277 (8.6%) had a tear alone, and 78 (2.4%) had neither episiotomy nor tear. Among women who experienced perineal trauma, amoxicillin and clavulanic acid administration was protective against infection in all subgroups compared with placebo with no significant interaction between subgroup and trial allocation (P=.17). Moreover, 2925 women were included in the multivariable risk factor analysis. The following were associated with adjusted risk ratios of infection: episiotomy, 2.94 (95% confidence interval, 1.62-5.31); forceps, 1.37 (95% confidence interval, 1.12-1.69) compared to vacuum extraction; primiparity, 1.34 (95% confidence interval, 1.05-1.70); amoxicillin and clavulanic acid administration, 0.60 (95% confidence interval, 0.51-0.72); body mass index of 25.0 to 29.9 kg/m CONCLUSION: Timely prophylactic antibiotics should be administered to all women after operative vaginal birth, irrespective of the type of perineal trauma. The use of episiotomy, forceps birth, primiparity, and overweight were associated with an increased risk of confirmed or suspected infection after operative vaginal birth. Prophylactic antibiotics in the prevention of infection after operative vaginal delivery (ANODE): a multicentre randomised controlled trial. BACKGROUND: Risk factors for maternal infection are clearly recognised, including caesarean section and operative vaginal birth. Antibiotic prophylaxis at caesarean section is widely recommended because there is clear systematic review evidence that it reduces incidence of maternal infection. Current WHO guidelines do not recommend routine antibiotic prophylaxis for women undergoing operative vaginal birth because of insufficient evidence of effectiveness. We aimed to investigate whether antibiotic prophylaxis prevented maternal infection after operative vaginal birth. METHODS: In a blinded, randomised controlled trial done at 27 UK obstetric units, women (aged ≥16 years) were allocated to receive a single dose of intravenous amoxicillin and clavulanic acid or placebo (saline) following operative vaginal birth at 36 weeks gestation or later. The primary outcome was confirmed or suspected maternal infection within 6 weeks of delivery defined by a new prescription of antibiotics for specific indications, confirmed systemic infection on culture, or endometritis. We did an intention-to-treat analysis. This trial is registered with ISRCTN, number 11166984, and is closed to accrual. FINDINGS: Between March 13, 2016, and June 13, 2018, 3427 women were randomly assigned to treatment: 1719 to amoxicillin and clavulanic acid, and 1708 to placebo. Seven women withdrew, leaving 1715 in the amoxicillin and clavulanic acid group and 1705 in the placebo groups. Primary outcome data were missing for 195 (6%) women. Significantly fewer women allocated to amoxicillin and clavulanic acid had a confirmed or suspected infection (180 [11%] of 1619) than women allocated to placebo (306 [19%] of 1606; risk ratio 0·58, 95% CI 0·49-0·69; p<0·0001). One woman in the placebo group reported a skin rash and two women in the amoxicillin and clavulanic acid reported other allergic reactions, one of which was reported as a serious adverse event. Two other serious adverse events were reported, neither was considered causally related to the treatment. INTERPRETATION: This trial shows benefit of a single dose of prophylactic antibiotic after operative vaginal birth and guidance from WHO and other national organisations should be changed to reflect this. FUNDING: NIHR Health Technology Assessment programme. Prophylactic antibiotics for the prevention of infection following operative vaginal delivery (ANODE): study protocol for a randomised controlled trial. BACKGROUND: Sepsis is one of the most important causes of maternal death and severe morbidity worldwide. Studies conducted both in the UK and US have documented an additional risk associated with operative vaginal delivery. However, a Cochrane review, updated in 2017, identified only one small trial of prophylactic antibiotics following operative vaginal delivery, which included a total of 393 women. Given the small size of that trial, it recommended that further robust evidence is needed. Operative vaginal delivery rates vary worldwide, but typically 5-10% of women have operative vaginal births. A conservative estimated incidence of maternal infection following operative vaginal delivery is 4%, based on the one previous trial. There is, therefore, considerable scope for direct patient benefit from an effective preventive strategy. METHODS/DESIGN: This protocol describes a multicentre, randomised, blinded, placebo-controlled trial aiming to recruit 3424 participants from over 20 hospital sites in the UK. Women who have undergone an operative vaginal delivery at 36 DISCUSSION: This randomised trial will investigate whether a prophylactic dose of antibiotic following operative vaginal delivery can reduce the incidence of infection and sepsis. If shown to be effective, this could lead to a change in recommended practice and the prevention of infection. Conversely, if there is no significant difference between the two arms, then this could contribute to a reduction in antibiotic use and improved antimicrobial stewardship. TRIAL REGISTRATION: ISRCTN11166984 . Registered on 23 September 2015. Efficacy of prophylactic antibiotics for the prevention of endomyometritis after forceps delivery. The purpose of this prospective randomized controlled clinical trial was to determine whether prophylactic antibiotics reduce the incidence of endomyometritis after forceps delivery. Of the 393 patients studied, 192 received 2 gm of intravenous cefotetan after forceps delivery, and 201 patients received no antibiotics. There were seven cases of endomyometritis in the group given no antibiotic and none in the cefotetan group, a statistically significant difference (P less than .01). We conclude that prophylactic antibiotics are effective in reducing the incidence of endomyometritis after forceps delivery. We believe this is the first published study demonstrating this benefit. Options: A: Prophylactic antibiotics significantly reduce superficial and deep perineal wound infections and serious infectious complications. B: Prophylactic antibiotics have no significant effect on reducing superficial and deep perineal wound infections or serious infectious complications. C: Prophylactic antibiotics increase the risk of superficial and deep perineal wound infections and serious infectious complications. D: Prophylactic antibiotics have a significant effect on reducing maternal adverse reactions and maternal length of stay.	A
4,613	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What were the findings regarding the comparison of nasogastric tube feeding and nasojejunal tube feeding in terms of mortality, morbidity, and nutritional status outcomes in people with severe acute pancreatitis? Please answer this question based on the information provided below: A randomized study of early nasogastric versus nasojejunal feeding in severe acute pancreatitis. BACKGROUND: After 50 yr in which nasoenteric feeding was considered contraindicated in acute pancreatitis (AP), several clinical studies have shown that early nasojejunal (NJ) feeding can be achieved in most patients. A pilot study of early nasogastric (NG) feeding in patients with objectively graded severe AP proved that this approach was also feasible. A randomized study comparing NG versus NJ feeding has been performed. METHODS: A total of 50 consecutive patients with objectively graded severe AP were randomized to receive either NG or NJ feeding via a fine bore feeding tube. The end points were markers of the acute phase response APACHE II scores and C-reactive protein (CRP) measurements, and pain patterns by visual analogue score (VAS) and analgesic requirements. Complications were monitored and comparisons made of both total hospital and intensive-care stays. RESULTS: A total of 27 patients were randomized to NG feeding and 23 to NJ. One of those in the NJ group had a false diagnosis, thereby reducing the number to 22. Demographics were similar between the groups and no significant differences were found between the groups in APACHE II score, CRP measurement, VAS, or analgesic requirement. Clinical differences between the two groups were not significant. Overall mortality was 24.5% with five deaths in the NG group and seven in the NJ group. CONCLUSIONS: The simpler, cheaper, and more easily used NG feeding is as good as NJ feeding in patients with objectively graded severe AP. This appears to be a useful and practical therapeutic approach to enteral feeding in the early management of patients with severe AP. Early enteral nutrition in severe acute pancreatitis: a prospective randomized controlled trial comparing nasojejunal and nasogastric routes. PURPOSE: Enteral nutrition (EN) is effective, easy to provide, cheaper, and associated with fewer complications in comparison with parenteral nutrition in severe acute pancreatitis (SAP). However, the nasogastric (NG) route for enteral supplements still remains to be established, and most studies have used the nasojejunal (NJ) route. The purpose of this study was to compare early NJ with NG feeding in SAP. PATIENTS AND METHODS: A total of 31 patients with SAP were randomized to feeding by either NG (15 patients) or NJ (16 patients). A semi-elemental formula was used through an enteral tube in both groups. Nutritional parameters (anthropometry, serum prealbumin and albumin levels) were recorded at baseline and after 7 days. Recurrence of pain and tolerance of feeding was noted. RESULTS: Recurrence of pain occurred in only 1 patient each in the 2 groups. Diarrhea occurred in 3 and 4 patients in the NJ and NG groups, respectively. There were 4 deaths in the NJ group and 5 in the NG group. Two patients in the NJ group and 1 in the NG group underwent surgery. There was no difference in the outcome measures (ie, discharge, surgery, and death). There was a decline in nutritional parameters in both groups. CONCLUSIONS: EN at a slow infusion is well tolerated by both NJ and NG routes in patients with SAP. Neither NJ nor NG feeding leads to recurrence or worsening of pain in SAP. Nutritional parameters remained unaffected because of inadequate calorie intake during the first week of feeding. Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: a noninferiority randomized controlled trial. OBJECTIVE: This study aimed to determine the noninferiority of early enteral feeding through nasogastric (NG) compared to nasojejunal (NJ) route on infectious complications in patients with severe acute pancreatitis (SAP). METHODS: Patients with SAP were fed via NG (candidate) or NJ (comparative) route. The primary outcome was the occurrence of any infectious complication in blood, pancreatic tissue, bile, or tracheal aspirate. Secondary end points were pain in refeeding, duration of hospital stay, intestinal permeability assessed by lactulose/mannitol excretion, and endotoxemia assessed by endotoxin core antibody types immunoglobulin G and M. RESULTS: Seventy-eight patients were randomized to feeding by either the NG or the NJ route. During the hospital stay, the presence of any infectious complication in the NG and NJ groups was 23.1% and 35.9% (significantly different), respectively. The effect size of the difference of infectious complications was -12.8 (95% confidence interval, -29.6 to 4.0). The upper limit of the 95% confidence interval was 4.0 and was within the 5% limit set for noninferiority. The value of 8.0 for the number needed to treat implies that 8 patients should be treated with NG compared with the NJ group to prevent 1 patient from any of the infectious complications. CONCLUSIONS: Early enteral feeding through NG was not inferior to NJ in patients with SAP. Infectious complications were within the noninferiority limit. Pain in refeeding, intestinal permeability, and endotoxemia were comparable in both groups. Options: A: Nasogastric tube feeding was found to be superior to nasojejunal tube feeding. B: Nasojejunal tube feeding was found to be superior to nasogastric tube feeding. C: There was insufficient evidence to determine superiority, inferiority, or equivalence between nasogastric and nasojejunal tube feeding. D: Both nasogastric and nasojejunal tube feeding were found to be equally effective.	C
4,614	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What were the findings regarding the effectiveness of physical therapies for managing postural abnormalities in people with cystic fibrosis, specifically in terms of quality of life, pain, trunk deformity, and pulmonary function? Please answer this question based on the information provided below: Musculoskeletal techniques for clinically stable adults with cystic fibrosis: a preliminary randomised controlled trial. AIMS: To assess the sensitivity of selected outcome measures to any change resulting from treatment of adults with cystic fibrosis with physiotherapy musculoskeletal techniques, use the data for sample size calculations for future studies and assess the acceptability of the methods to potential participants. DESIGN: Preliminary, prospective, single-blind, randomised controlled trial. SETTING: Specialist cystic fibrosis centre. PARTICIPANTS: Adults recruited from a cystic fibrosis outpatient clinic. INTERVENTIONS: The control group received normal optimal physiotherapy care and the intervention group received weekly musculoskeletal treatment for 6 weeks in addition to normal optimal physiotherapy care. OUTCOME MEASURES: Recorded at baseline, 3, 6 and 12 weeks. The outcome measures were posture (thoracic index), chest wall excursion, forced expiratory volume in 1 second (FEV₁), visual analogue scale for pain, modified shuttle test and Cystic Fibrosis Quality of Life Questionnaire--Section One (physical functioning). STATISTICAL ANALYSIS: Descriptive statistics [using medians and interquartile ranges (IQRs)] and linear regression mixed model. RESULTS: From a total of 20 subjects, 10 were randomised to each group. Fifty percent of subjects were male, with a median age of 27 years (IQR 25 to 34), median FEV(1) of 1.75 l (IQR 1.4 to 2.4) and median body mass index of 20.8 (IQR 20.0 to 23.5). Baseline differences between groups in thoracic index and modified shuttle test made any differences difficult to interpret, but the results for thoracic index and chest wall excursion at the third rib in the treatment group showed a trend towards improvement. The usefulness of FEV₁, the visual analogue scale for pain and the Cystic Fibrosis Quality of Life Questionnaire as measures is unclear. CONCLUSION: Further musculoskeletal studies in people with cystic fibrosis should consider using thoracic index and a measure of lung function in addition to FEV₁. The musculoskeletal techniques appear to be acceptable to people with cystic fibrosis, and do not seem to have associated adverse effects. Options: A: Physical therapies significantly improved quality of life, reduced pain, corrected trunk deformity, and enhanced pulmonary function. B: Physical therapies had no significant impact on quality of life, pain, trunk deformity, or pulmonary function. C: Physical therapies may make little or no difference to trunk deformity, and the evidence is very low quality for their impact on quality of life, pain, and pulmonary function. D: Physical therapies worsened the postural abnormalities and decreased pulmonary function in people with cystic fibrosis.	C
4,615	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What are the effects of enteral lactoferrin supplementation on late-onset sepsis, necrotizing enterocolitis (NEC), and all-cause mortality in preterm infants? Please answer this question based on the information provided below: Oral lactoferrin to prevent nosocomial sepsis and necrotizing enterocolitis of premature neonates and effect on T-regulatory cells. OBJECTIVE: Lactoferrin (LF) is effective in the prevention of sepsis in very low birth weight (VLBW) neonates. T-regulatory cells (Tregs) are important subsets of T lymphocytes that control pathogen-specific immune responses and are essential for intestinal immune homoeostasis. The aim of the present study is to determine whether oral LF at a dosage of 200 mg/d reduces nosocomial sepsis episodes and necrotizing enterocolitis (NEC) in premature infants and to evaluate the possible effects of LF on Treg levels. STUDY DESIGN: In this prospective, placebo-controlled, double-blind, randomized trial, infants either VLBW or born before 32 weeks were assigned to receive either placebo (n = 25), or 200 mg LF (n = 25) daily throughout hospitalization. Episodes of culture proven nosocomial sepsis and NEC were recorded. The level of FOXP3 + CD4 + CD25hi lymphocytes was studied by flow cytometry at birth and discharge. A third comparison was made with healthy term neonates (n = 16). RESULTS: Fewer sepsis episodes were observed in LF-treated infants (4.4 vs. 17.3/1,000 patient days, p = 0.007) with none developing NEC, without statistical significance. Treg levels at birth and discharge were similar, while preterm infants showed significantly lower levels than term controls. However, individual increases in Treg levels were higher in the LF group. CONCLUSION: LF prophylaxis reduced nosocomial sepsis episodes. Treg levels in preterm infants were lower than in term infants and an increase of Treg levels under LF prophylaxis was observed. Increase in Treg levels can be the mechanism for protective effects of LF on nosocomial sepsis. The Lacuna Trial: a double-blind randomized controlled pilot trial of lactoferrin supplementation in the very preterm infant. OBJECTIVE: To determine tolerability of bovine lactoferrin (bLF) in very preterm infants, and whether the intervention can be adequately masked. STUDY DESIGN: In a single-center masked pilot trial infants under 31 weeks gestation were randomized before 48 h of age to receive milk with 100 mg per day of bLF or control. The primary outcome was feeding tolerance, defined as time to achieve full feeds (140 ml kg(-1) per day). Parents answered a short questionnaire regarding acceptability of the intervention. RESULTS: Seventy-nine infants were enrolled and analyzed according to intention to treat. There was no effect of bLF on the primary outcome. In addition, mortality, late onset sepsis and other complications of prematurity were no different. Equal numbers of parents in both groups believed their infant received bLF. CONCLUSION: We demonstrated that bLF is well tolerated, easy to administer and its presence in prepared milk is not evident. Trial registration number ISRCTN66482337. Efficacy of Bovine Lactoferrin Supplementation in Preventing Late-onset Sepsis in low Birth Weight Neonates: A Randomized Placebo-Controlled Clinical Trial. OBJECTIVES: To evaluate the efficacy of bovine lactoferrin (BLF) in preventing first episode of late-onset sepsis (LOS) in low birth weight (LBW) neonates. METHODS: In this study conducted from May 2012 to July 2013 in the neonatal intensive care unit (NICU) of a tertiary care hospital, inborn asymptomatic neonates, <2000 g, admitted to NICU in first 12 h of birth with no maternal risk factors for sepsis were randomized to receive BLF or placebo from 1st to 28th day of life. The incidence of culture-proven sepsis and sepsis-attributable mortality after 72 h of life was recorded. Increasing doses of BLF were used with higher birth weights. RESULTS: Incidence of first episode of culture-proven LOS was significantly lower in the BLF group vs. placebo [2/63 (3.2%) vs. 9/67(13.4%); risk ratio, 0.211; 95% CI, 0.044-1.019; p = 0.036]. Statistically significant reduction in the sepsis-attributable mortality was also seen after use of prophylactic BLF [0/63 (0%) vs. 5/67 (7.5%); p = 0.027]. CONCLUSION: BLF supplementation in LBW neonates reduced the incidence of first episode of LOS. The effect of lactoferrin supplementation on death or major morbidity in very low birthweight infants (LIFT): a multicentre, double-blind, randomised controlled trial. BACKGROUND: Very low birthweight or preterm infants are at increased risk of adverse outcomes including sepsis, necrotising enterocolitis, and death. We assessed whether supplementing the enteral diet of very low-birthweight infants with lactoferrin, an antimicrobial protein, reduces all-cause mortality or major morbidity. METHODS: We did a multicentre, double-blind, pragmatic, randomised superiority trial in 14 Australian and two New Zealand neonatal intensive care units. Infants born weighing less than 1500 g and aged less than 8 days, were eligible and randomly assigned (1:1) using minimising web-based randomisation to receive once daily 200 mg/kg pasteurised bovine lactoferrin supplements or no lactoferrin supplement added to breast or formula milk until 34 weeks' post-menstrual age (or for 2 weeks, if longer), or until discharge from the study hospital if that occurred first. Designated nurses preparing the daily feeds were not masked to group assignment, but other nurses, doctors, parents, caregivers, and investigators were unaware. The primary outcome was survival to hospital discharge or major morbidity (defined as brain injury, necrotising enterocolitis, late-onset sepsis at 36 weeks' post-menstrual age, or retinopathy treated before discharge) assessed in the intention-to-treat population. Safety analyses were by treatment received. We also did a prespecified, PRISMA-compliant meta-analysis, which included this study and other relevant randomised controlled trials, to estimate more precisely the effects of lactoferrin supplementation on late-onset sepsis, necrotising enterocolitis, and survival. This trial is registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12611000247976. FINDINGS: Between June 27, 2014, and Sept 1, 2017, we recruited 1542 infants; 771 were assigned to the intervention group and 771 to the control group. One infant who had consent withdrawn before beginning lactoferrin treatment was excluded from analysis. In-hospital death or major morbidity occurred in 162 (21%) of 770 infants in the intervention group and in 170 (22%) of 771 infants in the control group (relative risk [RR] 0·95, 95% CI 0·79-1·14; p=0·60). Three suspected unexpected serious adverse reactions occurred; two in the lactoferrin group, namely unexplained late jaundice and inspissated milk syndrome, but were not attributed to the intervention and one in the control group had fatal inspissated milk syndrome. Our meta-analysis identified 13 trials completed before Feb 18, 2020, including this Article, in 5609 preterm infants. Lactoferrin supplements significantly reduced late-onset sepsis (RR 0·79, 95% CI 0·71-0·88; p<0·0001; I INTERPRETATION: Lactoferrin supplementation did not improve death or major morbidity in this trial, but might reduce late-onset sepsis, as found in our meta-analysis of over 5000 infants. Future collaborative studies should use products with demonstrated biological activity, be large enough to detect moderate and clinically important effects reliably, and assess greater doses of lactoferrin in infants at increased risk, such as those not exclusively receiving breastmilk or infants of extremely low birthweight. FUNDING: Australian National Health and Medical Research Council. Bovine lactoferrin supplementation for prevention of necrotizing enterocolitis in very-low-birth-weight neonates: a randomized clinical trial. IMPORTANCE: NEC is a common and severe complication in premature neonates, particularly those with very-low-birth-weight (VLBW, <1500 g at birth). Probiotics including lactobacillus rhamnosus GG (LGG) proved effective in preventing NEC in preterm infants in several RCTs. OBJECTIVE: Lactoferrin, a mammalian milk glycoprotein involved in innate immune host defences, can reduce the incidence of NEC in animal models, and its action is enhanced by LGG. We tried to assess whether bovine lactoferrin (BLF), alone or with the probiotic LGG, has a similar effect in human infants, something that has not yet been studied. DESIGN: An international, multicenter, randomized, double-blind, placebo-controlled trial conducted from October 1st, 2007 through July 31st, 2010. SETTING: Thirteen Italian and New Zealand tertiary neonatal intensive care units. PARTICIPANTS: 743 VLBW neonates were assessed until discharge for development of NEC. INTERVENTION: Infants were randomly assigned to receive orally either BLF (100 mg/day) alone (group LF; n = 247) or with LGG (at 6×10(9) CFU/day; group BLF + LGG; n = 238), or placebo (Control group; n = 258) from birth until day 30 of life (45 for neonates <1000 g at birth). MAIN OUTCOME MEASURES: ≥ stage 2 NEC; death-and/or-≥ stage 2 NEC prior to discharge. RESULTS: Demographics, clinical and management characteristics of the 3 groups were similar, including type of feeding and maternal milk intakes. NEC incidence was significantly lower in groups BLF and BLF + LGG [5/247 (2.0%)] and 0/238 (0%), respectively] than in controls [14/258 (5.4%)] (RR = 0.37; 95% CI: 0.136-1.005; p = 0.055 for BLF vs. control; RR = 0.00; p < 0.001 for BLF + LGG vs. control). The incidence of death-and/or-NEC was significantly lower in both treatment groups (4.0% and 3.8% in BLF and BLF + LGG vs. 10.1% in control; RR = 0.39; 95% CI: 0.19-0.80; p = 0.008. RR = 0.37; 95% CI: 0.18-0.77; p = 0.006, respectively). No adverse effects or intolerances to treatment occurred. CONCLUSIONS AND RELEVANCE: Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of ≥ stage 2 NEC and of death-and/or ≥ stage 2 NEC in VLBW neonates. BLF might be a promising strategy to prevent NEC in NICU settings. Further data on larger sample sizes are warranted before BLF can be widespreadly used in clinical settings. TRIAL REGISTRATION: ISRCTN53107700-http://www.controlled-_trials.com/ISRCTN53107700. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. CONTEXT: Sepsis is a common and severe complication in premature neonates, particularly those with very low birth weight (VLBW) (<1500 g). Whether lactoferrin, a mammalian milk glycoprotein involved in innate immune host defenses, can reduce the incidence of sepsis is unknown. In animal models, the probiotic Lactobacillus rhamnosus GG (LGG) enhances the activity of lactoferrin but has not been studied in human infants. OBJECTIVE: To establish whether bovine lactoferrin (BLF), alone or in combination with LGG, reduces the incidence of late-onset sepsis in VLBW neonates. DESIGN, SETTING, AND PATIENTS: Prospective, multicenter, double-blind, placebo-controlled, randomized trial conducted in 11 Italian tertiary neonatal intensive care units. Patients were 472 VLBW infants enrolled from October 1, 2007, through July 31, 2008, and assessed until discharge for development of sepsis. INTERVENTION: Infants were randomly assigned to receive orally administered BLF (100 mg/d) alone (n = 153), BLF plus LGG (6 x 10(9) colony-forming units/d) (n = 151), or placebo (n = 168) from birth until day 30 of life (day 45 for neonates <1000 g at birth). MAIN OUTCOME MEASURE: First episode of late-onset sepsis, ie, sepsis occurring more than 72 hours after birth with isolation of any pathogen from blood or from peritoneal or cerebrospinal fluid. RESULTS: Demographic, clinical, and management characteristics of the 3 groups were similar, including type of feeding and intake of maternal milk. Incidence of late-onset sepsis was significantly lower in the BLF and BLF plus LGG groups (9/153 [5.9%] and 7/151 [4.6%], respectively) than in the control group receiving placebo (29/168 [17.3%]) (risk ratio, 0.34; 95% confidence interval, 0.17-0.70; P = .002 for BLF vs control and risk ratio, 0.27; 95% confidence interval, 0.12-0.60; P < .001 for BLF plus LGG vs control). The decrease occurred for both bacterial and fungal sepsis. No adverse effects or intolerances to treatment occurred. CONCLUSION: Compared with placebo, BLF supplementation alone or in combination with LGG reduced the incidence of a first episode of late-onset sepsis in VLBW neonates. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN53107700. Bovine lactoferrin prevents invasive fungal infections in very low birth weight infants: a randomized controlled trial. BACKGROUND: Lactoferrin is a mammalian milk glycoprotein involved in innate immunity. Recent data show that bovine lactoferrin (bLF) prevents late-onset sepsis in preterm very low birth weight (VLBW) neonates. METHODS: This is a secondary analysis of data from a multicenter randomized controlled trial where preterm VLBW neonates randomly received bLF (100 mg/day; group A1), bLF + Lactobacillus rhamnosus GG (10(6) colony-forming units per day; group A2), or placebo (group B) for 6 weeks. Here we analyze the incidence rates of fungal colonization, invasive fungal infection (IFI), and rate of progression from colonization to infection in all groups. RESULTS: This study included 472 neonates whose clinical, nutritional, and demographical characteristics were similar. Overall, the incidence of fungal colonization was comparable (17.6%, 16.6%, and 18.5% in A1, A2, and B, respectively; P = .89 [A1] and .77 [A2]). In contrast, IFIs were significantly decreased in A1 and A2 (0.7% and 2.0%, respectively) compared with B (7.7%; P = .002 [A1] and .02 [A2]), and this was significantly true both in <1000 g (0.9% [A1] and 5.6% [A2], vs 15.0%) and in 1001 to 1500 g infants (0% and 0% vs 3.7%). The progression rate colonization-infection was significantly lower in the bLF groups: 3.7% (A1) and 12% (A2), vs 41.9%; P < .001 (A1) and P = .02 (A2). No IFI-attributable deaths occurred in the treatment groups, versus 2 in placebo. No adverse effects or intolerances occurred. CONCLUSIONS: Prophylactic oral administration of bLF reduces the incidence of IFI in preterm VLBW neonates. No effect is seen on colonization. The protective effect on IFI is likely due to limitation of ability of fungal colonies to progress toward invasion and systemic disease in colonized infants. Randomized controlled trial of lactoferrin for prevention of sepsis in peruvian neonates less than 2500 g. BACKGROUND: Lactoferrin (LF) is a broad-spectrum antimicrobial and immunomodulatory milk glycoprotein. OBJECTIVE: To determine the effect of bovine LF on the prevention of the first episode of late-onset sepsis in Peruvian infants. METHODS: We conducted a pilot randomized placebo-controlled double blind study in infants with a birth weight (BW) less than 2500g in 3 Neonatal Units in Lima. Patients were randomized to receive bovine LF 200mg/kg/d or placebo for 4 weeks. RESULTS: One hundred and ninety neonates with a BW of 1591 ± 408 g and a gestational age of 32.1 ± 2.6 weeks were enrolled. Overall, 33 clinically defined first late-onset sepsis events occurred. The cumulative sepsis incidence in the LF group was 12/95 (12.6%) versus 21/95 (22.1%) in the placebo group, and 20% (8/40) versus 37.5% (15/40) for infants less than or equal to 1500 g. The hazard ratio of LF, after adjustment by BW, was 0.507 (95% CI: 0.249-1.034). There were 4 episodes of culture-proven sepsis in the LF group versus 4 in the placebo group. Considering that children did not received the intervention until the start of oral or tube feeding, we ran a secondary exploratory analysis using time since the start of the treatment; in this model, LF achieved significance. There were no serious adverse events attributable to the intervention. CONCLUSIONS: Overall sepsis occurred less frequently in the LF group than in the control group. Although the primary outcome did not reach statistical significance, the confidence interval is suggestive of an effect that justifies a larger trial. Randomized Controlled Trial of Bovine Lactoferrin for Prevention of Sepsis and Neurodevelopment Impairment in Infants Weighing Less Than 2000 Grams. OBJECTIVES: To determine the effect of bovine lactoferrin on prevention of late-onset sepsis (LOS) and neurodevelopment delay. STUDY DESIGN: Randomized, double-blind, controlled trial in neonates with a birth weight of 500-2000 g in 3 neonatal units in Lima, Peru, comparing bovine lactoferrin 200 mg/kg/day with placebo administered for 8 weeks. The primary outcome was the first episode of culture-proven LOS or sepsis-associated death. Neurodevelopment delay was assessed by the Mullen Scales at 24 months corrected age. RESULTS: Of the 414 infants enrolled, 209 received bovine lactoferrin and 205 received placebo. LOS or sepsis-associated death occurred in 22 infants (10.5%) in the bovine lactoferrin group vs 30 (14.6%) in the placebo group; there was no difference after adjusting for hospital and birth weight; hazard ratio 0.73 (95% CI, 0.42-1.26). For infants with birth weights of <1500 g the hazard ratio was 0.69 (95% CI, 0.39-1.25). The mean age-adjusted normalized Mullen composite score at 24 months was 83.3 ± 13.6 in the bovine lactoferrin group vs 82.6 ± 13.1 in the placebo group. Growth outcomes and rehospitalization rates during the 2-year follow-up were similar in both groups, except for significantly less bronchiolitis in the bovine lactoferrin group (rate ratio, 0.34; 95% CI, 0.14-0.86). CONCLUSIONS: Supplementation with bovine lactoferrin did not decrease the incidence of sepsis in infants with birth weights of <2000 g. Growth and neurodevelopment outcomes at 24 months of age were similar. Neonatal bovine lactoferrin supplementation had no adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01525316. Randomized Controlled Trial of Talactoferrin Oral Solution in Preterm Infants. OBJECTIVE: To evaluate the safety and explore the efficacy of recombinant human lactoferrin (talactoferrin [TLf]) to reduce infection. STUDY DESIGN: We conducted a randomized, double blind, placebo-controlled trial in infants with birth weight of 750-1500 g. Infants received enteral TLf (n = 60) or placebo (n = 60) on days 1 through 28 of life; the TLf dose was 150 mg/kg every 12 hours. Primary outcomes were bacteremia, pneumonia, urinary tract infection, meningitis, and necrotizing enterocolitis (NEC). Secondary outcomes were sepsis syndrome and suspected NEC. We recorded clinical, laboratory, and radiologic findings, along with diseases and adverse events, in a database used for statistical analyses. RESULTS: Demographic data were similar in the 2 groups of infants. We attributed no enteral or organ-specific adverse events to TLf. There were 2 deaths in the TLf group (1 each due to posterior fossa hemorrhage and postdischarge sudden infant death), and 1 death in the placebo group, due to NEC. The rate of hospital-acquired infections was 50% lower in the TLf group compared with the placebo group (P < .04), including fewer blood or line infections, urinary tract infections, and pneumonia. Fourteen infants in the TLf group weighing <1 kg at birth had no gram-negative infections, compared with only 3 of 14 such infants in the placebo group. Noninfectious outcomes were not statistically significantly different between the 2 groups, and there were no between-group differences in growth or neurodevelopment over a 1-year posthospitalization period. CONCLUSION: We found no clinical or laboratory toxicity and a trend toward less infectious morbidity in the infants treated with TLf. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00854633. Options: A: Lactoferrin supplementation decreases late-onset sepsis, NEC stage II or III, and all-cause mortality. B: Lactoferrin supplementation decreases late-onset sepsis but has no effect on NEC stage II or III or all-cause mortality. C: Lactoferrin supplementation has no effect on late-onset sepsis, NEC stage II or III, or all-cause mortality. D: Lactoferrin supplementation increases late-onset sepsis, NEC stage II or III, and all-cause mortality.	B
4,616	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the effectiveness of interventions in preventing Sudden Unexpected Death in Epilepsy (SUDEP) in people with epilepsy? Please answer this question based on the information provided below: Case-control study of SUDEP. OBJECTIVE: To examine the influence of various factors on the risk of sudden unexpected death in epilepsy (SUDEP). METHODS: The authors investigated 154 cases in which a postmortem examination was performed. Each case had four controls with epilepsy from the community, matched for age and geographic location. Backward stepwise conditional logistic regression analysis was performed and odds ratios for risk and protection were determined. RESULTS: The risk of SUDEP was increased with a history of generalized tonic-clonic seizures in the previous 3 months (odds ratio [OR]: 13.8, 95% CI: 6.6 to 29.1). The presence of supervision at night was found to be protective (OR: 0.4, 95% CI: 0.2 to 0.8) when a supervising individual shared the same bedroom or when special precautions such as a listening device were employed (OR: 0.1, 95% CI: 0.0 to 0.3). CONCLUSION: This work lends support to the view that SUDEP is a seizure-related phenomenon and that control of tonic-clonic seizures is important in its prevention. Nocturnal supervision seems to protect against SUDEP. Effect of providing sudden unexpected death in epilepsy (SUDEP) information to persons with epilepsy (PWE) and their caregivers-Experience from a tertiary care hospital. OBJECTIVE: The primary objective of present study was to observe the effect of providing SUDEP (Sudden Unexpected Death in Epilepsy) information on drug adherence in persons with epilepsy (PWE). We also looked at impact of disclosing SUDEP information on patient's quality of life and mood. MATERIAL AND METHODS: This prospective study had a pretest/post-test design. A total of 231 consecutive PWE (>15 years) were enrolled. Of these 121 PWE received information about SUDEP in addition to standard epilepsy care. One hundred and ten PWE (control group) received routine standard epilepsy care but did not receive SUDEP information. Follow up assessment was done at 6 months. The primary outcome was a change in drug adherence (measured by Modified Morisky Medication Adherence Scale, MMAS) in PWE following disclosure of SUDEP information. RESULTS: After 6 months, 116 PWE in the SUDEP information group and 106 in control group were available for follow up. A non-significant higher adherence was observed in the SUDEP information group as compared to the control group (Mean MMAS change 0.51 ± 1.66 vs 0.25 ± 1.26, P value = 0.194). No significant change was perceived in patient's anxiety and depression levels or quality of life in either group. CONCLUSION: The present study suggests that providing information on SUDEP to PWE and their caregivers may increase drug adherence without adverse effect on quality of life or mood. Well-designed studies with high methodological quality are required to determine the precise effect size associated with disclosure of SUDEP information on drug adherence in PWE. Steps to prevent SUDEP: the validity of risk factors in the SUDEP and seizure safety checklist: a case control study. Our objectives were to compare people with epilepsy (PWE) who died of sudden unexpected death in epilepsy (SUDEP) with live controls using the risk factor items of the SUDEP and Seizure Safety Checklist. All 48 SUDEPs of 93 epilepsy deaths which occurred in Cornwall UK 2004-2012 were compared to 220 live controls using the SUDEP and Seizure Safety Checklist, an evidenced based tool used to communicate person centered risk of SUDEP to PWE. The odds ratio for having a specific factor in those who died was compared to controls and ranked according to P value using a sequential Bonferroni correction for multiple comparisons. Of the 17 modifiable and non-modifiable risk factors analyzed 9 were statistically significant of which 7 are potentially modifiable. Well known modifiable factors such as nocturnal monitoring, compliance and sleeping position featured prominently in the risk association. This is the first case control study exploring the risk factors for SUDEP since 2009. The findings are compared to the current considered risk factors as identified in a major recent review. The study further validates certain SUDEP risk factors. It highlights that the majority of risk factors strongly associated with SUDEP are potentially modifiable. There is an emerging profile to rank the risk factors. It furthers the evidence to use structured risk assessment and communication tools such as the SUDEP and Seizure Safety Checklist in daily clinical practice. It highlights key areas for a person centered discussion to empower PWE to mitigate risk. Nocturnal supervision and SUDEP risk at different epilepsy care settings. OBJECTIVE: To estimate the incidence of sudden unexpected death in epilepsy (SUDEP) in people with intellectual disabilities in residential care settings and to ascertain the effects of nocturnal seizures and nocturnal supervision on SUDEP risk. METHODS: We conducted a nested case-control study reviewing records of all people who died at 2 residential care settings over 25 years. Four controls per case were selected from the same population, matched on age (±5 years) and residential unit. Nocturnal supervision was graded in 3 categories: (1) no supervision; (2) a listening device or a roommate or physical checks at least every 15 minutes; and (3) 2 of the following: a listening device, roommate, additional device (bed motion sensor/video monitoring), or physical checks every 15 minutes. Outcome measures were compared using Mann-Whitney RESULTS: We identified 60 SUDEP cases and 198 matched controls. People who died of SUDEP were more likely to have nocturnal convulsive seizures in general (77% of cases vs 33% of controls, CONCLUSIONS: Having nocturnal seizures, in particular convulsions, may increase SUDEP risk. Different levels of nocturnal supervision may account for some of the difference in incidence. Options: A: No interventions have been found to be effective in preventing SUDEP. B: Supervision at night has been found to reduce the incidence of SUDEP. C: Selective serotonin reuptake inhibitors (SSRIs) have been found to be the most effective intervention in preventing SUDEP. D: Early surgical evaluation is the only effective intervention in preventing SUDEP.	B
4,617	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the effectiveness of prescription spectacles compared with no intervention for the prevention of strabismus in infants and children with hyperopia? Please answer this question based on the information provided below: Normal emmetropization in infants with spectacle correction for hyperopia. PURPOSE: The development of emmetropic refraction is known to be under visual control. Does partial spectacle correction of infants' refractive errors, which has been shown to have beneficial effects in reducing strabismus and amblyopia, impede emmetropization? The purpose of the present study was to perform the first longitudinal controlled trial to investigate this question in human subjects. METHODS: Children identified as having significant hyperopia in a population screening program at age 8 to 9 months were assigned to treated (partial spectacle correction) or untreated groups. A control group of infants with no significant refractive errors at screening was also recruited. Measurements of retinoscopic refraction under cycloplegia were taken at 4- to 6-month intervals up to the age of 36 months, and changes in refraction of 148 subjects were analyzed longitudinally. RESULTS: Refractive error decreased toward low hyperopic values between 9 and 36 months in both hyperopic groups. By 36 months, this reduction of hyperopia showed no overall difference between children who were treated with partial spectacle correction and those who were not. Despite the improvement, both hyperopic groups' mean refractive error at 36 months remained higher than that of the control group. When infants in all three groups were considered together, the rate of reduction of refractive error was, on average, a linear function of the initial level of hyperopia. CONCLUSIONS: The benefits of spectacle correction for infants with hyperopia can be achieved without impairing the normal developmental regulation of refraction. Infant hyperopia: detection, distribution, changes and correlates-outcomes from the cambridge infant screening programs. PURPOSE: To report on two population screening programs designed to detect significant refractive errors in 8308 8- to 9-month-old infants, examine the sequelae of infant hyperopia, and test whether early partial spectacle correction improved visual outcome (strabismus and acuity). The second program also examined whether infant hyperopia was associated with developmental differences across various domains such as language, cognition, attention, and visuomotor competences up to age 7 years. Linked programs in six European countries assessed costs of infant refractive screening. METHOD: In the first program, screening included an orthoptic examination and isotropic photorefraction, with cycloplegia. In the second program we carried out the same screening procedure without cycloplegia. Hyperopic infants (> or = +4 D) were followed up alongside an emmetropic control group, with visual and developmental measures up to age 7 years, and entered a controlled trial of partial spectacle correction. RESULTS: The second program showed that accommodative lag during photorefraction with a target at 75 cm (focus > or = +1.5 D) was a marker for significant hyperopia. In each program, prevalence of significant hyperopia at 9 to 11 months was around 5%; manifest strabismus was 0.3% at 9 months and 1.5 to 2.0% by school age. Infant hyperopia was associated with increased strabismus and poor acuity at 4 years. Spectacle wear by infant hyperopes produced better visual outcome than in uncorrected infants, although an improvement in strabismus was found in the first program only. The corrections did not affect emmetropization to 3.5 years; however, both corrected and uncorrected groups remained more hyperopic than controls in the preschool years. The hyperopic group showed poorer overall performance than controls between 1 and 7 years on visuoperceptual, cognitive, motor, and attention tests, but showed no consistent differences in early language or phonological awareness. Relative cost estimates suggest that refractive screening programs can detect visual problems in infancy at lower overall cost than surveillance in primary care. CONCLUSIONS: Photo/videorefraction can successfully screen infants for refractive errors, with visual outcomes improved through early refractive correction. Infant hyperopia is associated with mild delays across many aspects of visuocognitive and visuomotor development. These studies raise the possibility that infant refractive screening can identify not only visual problems, but also potential developmental and learning difficulties. Two infant vision screening programmes: prediction and prevention of strabismus and amblyopia from photo- and videorefractive screening. Two infant vision screening programmes on total populations in the Cambridge Health District have been designed to identify manifest strabismus and strabismogenic and amblyogenic refractive errors at 7-9 months of age. The first, completed, programme used the isotropic photorefractor with cycloplegia together with a standard orthoptic examination. The second, current, programme uses the VRP-1 isotropic videorefractor to identify infants with accommodative lags which are followed up by refraction under cycloplegia. Both programmes show good agreement between infants identified at screening and retinoscopic refractions at follow-up, showing that photo- and videorefraction (with or without cycloplegia) can be effective methods for screening for ametropia in infants and young children. In each programme 5-6% of infants showed abnormal levels of hyperopia (> or = 3.5 D in any meridian), less than 1% showed anisometropia > or = 1.5 D; very few infants (0.25%) showed -3D myopia or greater. Less than 1% showed manifest strabismus. Hyperopic and anisometropic children entered a randomised controlled trial of partial refractive correction. All children identified at screening, alongside appropriate control groups, are extensively followed up to age 4 years. The first programme has found that children who were hyperopic in infancy were 13 times more likely to become strabismic, and 6 times more likely to show measurable acuity deficits by 4 years, compared with controls. Wearing a partial spectacle correction reduced these risk ratios to 4:1 and 2.5:1 respectively. The impaired acuity can be attributed, in part, to meridional amblyopia resulting from persisting astigmatism. Both hyperopic and myopic infants showed refractive changes in the direction of emmetropia between 9 months and 4 years. Wearing a partial spectacle correction did not affect this process of emmetropisation, but does provide the possibility of reducing the incidence of common pre-school vision problems. A Randomized Clinical Trial of Immediate versus Delayed Glasses for Moderate Hyperopia in 1- and 2-Year-Olds. PURPOSE: Two strategies were compared for managing moderate hyperopia without manifest strabismus among 1- and 2-year-old children: (1) immediate prescription of glasses versus (2) observation without glasses unless reduced distance visual acuity (VA), reduced stereoacuity, or manifest strabismus. DESIGN: Prospective randomized clinical trial. PARTICIPANTS: A total of 130 children aged 1 to 2 years with hyperopia between +3.00 diopters (D) and +6.00 D spherical equivalent (SE) in at least 1 eye, anisometropia ≤1.50 D SE, and astigmatism ≤1.50 D based on cycloplegic refraction and no manifest strabismus. METHODS: Participants were randomly assigned to glasses (1.00 D less than full cycloplegic hyperopia) versus observation and followed every 6 months for 3 years. Glasses were prescribed to those assigned to observation if they met prespecified deterioration criteria of distance VA or near stereoacuity below age norms, or development of manifest strabismus. MAIN OUTCOME MEASURES: At the 3-year primary outcome examination, participants were classified as failing the randomized management regimen if distance VA or stereoacuity was below age norms or manifest strabismus was observed (each with and without correction in trial frames, confirmed by masked retest, irrespective of whether deterioration had occurred previously), or if strabismus surgery had been performed. RESULTS: Of the 106 participants (82%) completing the 3-year primary outcome examination, failure occurred in 11 (21%) of 53 in the glasses group and 18 (34%) of 53 in the observation group (difference = -13%; 95% confidence interval [CI], -31 to 4; P = 0.14). Sixty-two percent (95% CI, 49-74) in the observation group and 34% (95% CI, 23-48) in the glasses group met deterioration criteria (requiring glasses if not wearing). CONCLUSIONS: For 1- and 2-year-olds with uncorrected moderate hyperopia (+3.00 D to +6.00 D SE), our estimates of failure, after 3 years of 6-month follow-ups, are inconclusive and consistent with a small to moderate benefit or no benefit of immediate prescription of glasses compared with careful observation (with glasses only if deteriorated). A first attempt to prevent amblyopia and squint by spectacle correction of abnormal refractions from age 1 year. Spectacle correction of unusually hypermetropic refractions from age 1 year did not reduce the incidence of squint or amblyopia, nor did it lead to a reduction in the severity of residual amblyopia after subsequent occlusion. Emmetropisation, squint, and reduced visual acuity after treatment. In a sample of children used to assess the value of optical correction of hypermetropia from the age of 6 months the refraction of the most hypermetropic meridian frequently became less than 3.5 D as the children grew. When this occurred, the incidence of squint was significantly less (p less than 0.001) and the last known acuity after treatment was significantly better (p less than 0.001) than when it did not. This process of emmetropisation appears to have been impeded by the consistent wearing of hypermetropic spectacle correction from the age of 6 months. Results of a randomised trial of treating abnormal hypermetropia from the age of 6 months. Children who were abnormally hypermetropic at the age of 6 months were randomly allocated treatment with spectacles or no treatment. The eventual incidence of squint was the same in both groups (approximately 24%). The last known visual acuity of the two groups was not significantly different either. Therefore there is no indication to screen infants with a view to preventing squint/amblyopia by optical correction of hypermetropia. If, however, the children allocated treatment are divided into two subgroups--those who wore glasses consistently and those who probably or certainly did not do so--the incidence of squint was the same, but the last known acuities of those who consistently wore glasses may be better than those who did not do so. This suggests that it may yet prove possible to prevent severe amblyopia. Effect of spectacles on changes of spherical hypermetropia in infants who did, and did not, have strabismus. AIM: To explore why emmetropisation fails in children who have strabismus. METHODS: 289 hypermetropic infants were randomly allocated spectacles and followed. Changes in spherical hypermetropia were compared in those who had strabismus and those who did not. The effect of wearing glasses on these changes was assessed using t tests and regression analysis. RESULTS: Mean spherical hypermetropia decreased in both eyes of "normal" children (p<0.001). The consistent wearing of glasses impeded this process in both eyes (p<0.007). In the children with strabismus, there were no significant changes in either eye, irrespective of treatment (p>0. 05). CONCLUSIONS: In contrast with normal infants, neither eye of those who had strabismus emmetropised, irrespective of whether the incoming vision was clear or blurred. It is suggested that these eyes did not "recognise" the signal of blurred vision, and that they remained long sighted because they were destined to squint. Hence, the children did not squint because they were long sighted, and glasses did not prevent them squinting. Reduction of astigmatism after infancy in children who did and did not wear glasses and have strabismus. The purpose of this study was to record and explain the changes in astigmatism as normal and strabismic infants grew. Two-hundred-and-eighty-nine hypermetropic infants were randomly allocated to wear glasses from the age of six months. Changes in astigmatism and in hypermetropia of the horizontal and vertical meridia were compared in those who did and did not wear glasses and have strabismus. Mean astigmatism decreased significantly (p < 0.001) in both eyes of normal and strabismic children, but the 'last' astigmatism was significantly (p < 0.001) larger in both eyes of those who had strabismus. There was a similar progressive decrease of hypermetropia in both meridia of both eyes within each diagnostic group, but with the exception of the vertical meridian of the non-fixating eyes (in which the difference approached statistical significance), this was significantly (p < 0.01) larger in the normal children. The consistent wear of glasses was not associated with change in both meridia of both eyes in the normal children (p < 0.005), but had no significant effect on the changes in astigmatism. Since the changes in the two meridia were proportional to the starting level, hypermetropia decreased more in the meridian which was, initially, the more hypermetropic one, and the difference between them, i.e. astigmatism, tended to disappear whether or not the child eventually had strabismus. Options: A: Prescription spectacles significantly reduce the incidence of strabismus in hyperopic children. B: Prescription spectacles have a clear and consistent benefit in preventing strabismus, amblyopia, and inadequate stereoacuity in hyperopic children. C: The effect of prescription spectacles on the prevention of strabismus, amblyopia, and inadequate stereoacuity in hyperopic children is unclear, with very low confidence in the evidence. D: Prescription spectacles impede the natural process of emmetropization in hyperopic children.	C
4,618	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What were the findings regarding the effectiveness of exercise in altering the occurrence, severity, or duration of acute respiratory infections (ARIs) in adults? Please answer this question based on the information provided below: Meditation or exercise for preventing acute respiratory infection: a randomized controlled trial. PURPOSE: This study was designed to evaluate potential preventive effects of meditation or exercise on incidence, duration, and severity of acute respiratory infection (ARI) illness. METHODS: Community-recruited adults aged 50 years and older were randomized to 1 of 3 study groups: 8-week training in mindfulness meditation, matched 8-week training in moderate-intensity sustained exercise, or observational control. The primary outcome was area-under-the-curve global illness severity during a single cold and influenza season, using the Wisconsin Upper Respiratory Symptom Survey (WURSS-24) to assess severity. Health care visits and days of missed work were counted. Nasal wash collected during ARI illness was assayed for neutrophils, interleukin-8, and viral nucleic acid. RESULTS: Of 154 adults randomized into the study, 149 completed the trial (82% female, 94% white, mean age 59.3 ± 6.6 years). There were 27 ARI episodes and 257 days of ARI illness in the meditation group (n = 51), 26 episodes and 241 illness days in the exercise group (n = 47), and 40 episodes and 453 days in the control group (n = 51). Mean global severity was 144 for meditation, 248 for exercise, and 358 for control. Compared with control, global severity was significantly lower for meditation (P = .004). Both global severity and total days of illness (duration) trended toward being lower for the exercise group (P=.16 and P=.032, respectively), as did illness duration for the meditation group (P=.034). Adjusting for covariates using zero-inflated multivariate regression models gave similar results. There were 67 ARI-related days of-work missed in the control group, 32 in the exercise group (P = .041), and 16 in the meditation group (P <.001). Health care visits did not differ significantly. Viruses were identified in 54% of samples from meditation, 42% from exercise, and 54% from control groups. Neutrophil count and interleukin-8 levels were similar among intervention groups. CONCLUSIONS: Training in meditation or exercise may be effective in reducing ARI illness burden. Advantage of meditation over exercise in reducing cold and flu illness is related to improved function and quality of life. PURPOSE: To examine whether apparent advantages following training in meditation over exercise can be attributed to specific symptoms, functional impairments, or quality-of-life indicators assessed by the Wisconsin Upper Respiratory Symptom Survey (WURSS-24). METHODS: Results from the randomized controlled trial "Meditation or Exercise for Preventing Acute Respiratory Illness" showed mean global severity and total days of illness were worse in control (358, 8·9) compared with exercise (248, 5·1) or meditation (144, 5·0). Global severity of illness was estimated using area under the curve from daily self-reported severity scores on the WURSS-24. For this project, we estimated within-group WURSS item-level severity and between-group effect sizes (Cohen's "d" statistic) relative to control. The item-level effect sizes were grouped into (i) symptom and (ii) function and quality of life domains. RESULTS: Among the three groups, mediators showed the lowest severity estimates for 21 of 22 WURSS items. Item-level Cohen's "d" indicated most benefit was evident in WURSS items representing function and quality of life. Compared with exercise, meditation fostered larger reductions in illness severity, although due mostly to improved function and the quality of life domain (d=-0·33, P<0·001) compared with symptom domain (d=-0·22, P<0·001). CONCLUSIONS: The apparent advantage of training in meditation over exercise for reducing cold and flu illness is explained more by improved function and quality of life than by a reduction in symptom severity. Value associated with mindfulness meditation and moderate exercise intervention in acute respiratory infection: the MEPARI Study. BACKGROUND AND OBJECTIVES: Acute respiratory infection (ARI) is among the most common, debilitating and expensive human illnesses. The purpose of this study was to assess ARI-related costs and determine if mindfulness meditation or exercise can add value. METHODS: One hundred and fifty-four adults ≥50 years from Madison, WI for the 2009-10 cold/flu season were randomized to (i) wait-list control (ii) meditation or (iii) moderate intensity exercise. ARI-related costs were assessed through self-reported medication use, number of missed work days and medical visits. Costs per subject were based on cost of generic medications, missed work days ($126.20) and clinic visits ($78.70). Monte Carlo bootstrap methods evaluated reduced costs of ARI episodes. RESULTS: The total cost per subject for the control group was $214 (95% CI: $105-$358), exercise $136 (95% CI: $64-$232) and meditation $65 (95% CI: $34-$104). The majority of cost savings was through a reduction in missed days of work. Exercise had the highest medication costs at $16.60 compared with $5.90 for meditation (P = 0.004) and $7.20 for control (P = 0.046). Combining these cost benefits with the improved outcomes in incidence, duration and severity seen with the Meditation or Exercise for Preventing Acute Respiratory Infection study, meditation and exercise add value for ARI. Compared with control, meditation had the greatest cost benefit. This savings is offset by the cost of the intervention ($450/subject) that would negate the short-term but perhaps not long-term savings. CONCLUSIONS: Meditation and exercise add value to ARI-associated health-related costs with improved outcomes. Further research is needed to confirm results and inform policies on adding value to medical spending. Randomized controlled trial of mindfulness meditation and exercise for the prevention of acute respiratory infection: possible mechanisms of action. Background. A randomized trial suggests that meditation and exercise may prevent acute respiratory infection (ARI). This paper explores potential mediating mechanisms. Methods. Community-recruited adults were randomly assigned to three nonblinded arms: 8-week mindfulness-based stress reduction (N = 51), moderate-intensity exercise (N = 51), or wait-list control (N = 52). Primary outcomes were ARI illness burden (validated Wisconsin Upper Respiratory Symptom Survey). Potential mediators included self-reported psychophysical health and exercise intensity (baseline, 9 weeks, and 3 months). A Baron and Kenny approach-based mediational analysis model, adjusted for group status, age, and gender, evaluated the relationship between the primary outcome and a potential mediator using zero-inflated modeling and Sobel testing. Results. Of 154 randomized, 149 completed the trial (51, 47, and 51 in meditation, exercise, and control groups) and were analyzed (82% female, 94% Caucasian, 59.3 ± SD 6.6 years old). Mediational analyses suggested that improved mindfulness (Mindful Attention Awareness Scale) at 3 months may mediate intervention effects on ARI severity and duration (P < 0.05); 1 point increase in the mindfulness score corresponded to a shortened ARI duration by 7.2-9.6 hours. Conclusions. Meditation and exercise may decrease the ARI illness burden through increased mindfulness. These preliminary findings need confirmation, if confirmed, they would have important policy and clinical implications. This trial registration was Clinicaltrials.gov: NCT01057771. Meditation or exercise for preventing acute respiratory infection (MEPARI-2): A randomized controlled trial. BACKGROUND: Practice of meditation or exercise may enhance health to protect against acute infectious illness. OBJECTIVE: To assess preventive effects of meditation and exercise on acute respiratory infection (ARI) illness. DESIGN: Randomized controlled prevention trial with three parallel groups. SETTING: Madison, Wisconsin, USA. PARTICIPANTS: Community-recruited adults who did not regularly exercise or meditate. METHODS: 1) 8-week behavioral training in mindfulness-based stress reduction (MBSR); 2) matched 8-week training in moderate intensity sustained exercise (EX); or 3) observational waitlist control. Training classes occurred in September and October, with weekly ARI surveillance through May. Incidence, duration, and area-under-curve ARI global severity were measured using daily reports on the WURSS-24 during ARI illness. Viruses were identified multiplex PCR. Absenteeism, health care utilization, and psychosocial health self-report assessments were also employed. RESULTS: Of 413 participants randomized, 390 completed the trial. In the MBSR group, 74 experienced 112 ARI episodes with 1045 days of ARI illness. Among exercisers, 84 had 120 episodes totaling 1010 illness days. Eighty-two of the controls had 134 episodes with 1210 days of ARI illness. Mean global severity was 315 for MBSR (95% confidence interval 244, 386), 256 (193, 318) for EX, and 336 (268, 403) for controls. A prespecified multivariate zero-inflated regression model suggested reduced incidence for MBSR (p = 0.036) and lower global severity for EX (p = 0.042), compared to control, not quite attaining the p<0.025 prespecified cut-off for null hypothesis rejection. There were 73 ARI-related missed-work days and 22 ARI-related health care visits in the MBSR group, 82 days and 21 visits for exercisers, and 105 days and 24 visits among controls. Viruses were identified in 63 ARI episodes in the MBSR group, compared to 64 for EX and 72 for control. Statistically significant (p<0.05) improvements in general mental health, self-efficacy, mindful attention, sleep quality, perceived stress, and depressive symptoms were observed in the MBSR and/or EX groups, compared to control. CONCLUSIONS: Training in mindfulness meditation or exercise may help protect against ARI illness. LIMITATIONS: This trial was likely underpowered. TRIAL REGISTRATION: Clinicaltrials.gov NCT01654289. Beverage Containing Dispersible Yeast β-Glucan Decreases Cold/Flu Symptomatic Days After Intense Exercise: A Randomized Controlled Trial. In this double-blind, randomized, placebo-controlled parallel study, we examined the effect of dairy-based beverages (250 mL/day) containing 250 mg of dispersible baker's yeast β-glucan (Wellmune) compared to a macronutrient- and calorie-matched control on upper respiratory tract infection (URTI) in marathon runners. Healthy adults running in the 2017 Austin Marathon consumed either β-glucan ( Moderate-intensity exercise reduces the incidence of colds among postmenopausal women. PURPOSE: Our aim was to assess the effect of a moderate-intensity, year-long exercise program on the risk of colds and other upper respiratory tract infections in postmenopausal women. SUBJECTS: A total of 115 overweight and obese, sedentary, postmenopausal women in the Seattle area participated. METHODS: Participants were randomly assigned to the moderate-intensity exercise group or the control group. The intervention consisted of 45 minutes of moderate-intensity exercise 5 days per week for 12 months. Control participants attended once-weekly, 45-minute stretching sessions. Questionnaires asking about upper respiratory tract infections in the previous 3 months were administered quarterly during the course of the year-long trial. Poisson regression was used to estimate the effect of exercise on colds and other upper respiratory tract infections. RESULTS: Over 12 months, the risk of colds decreased in exercisers relative to stretchers (P = .02): In the final 3 months of the study, the risk of colds in stretchers was more than threefold that of exercisers (P = .03). Risk of upper respiratory tract infections overall did not differ (P = .16), yet may have been biased by differential proportions of influenza vaccinations in the intervention and control groups. CONCLUSIONS: This study suggests that 1 year of moderate-intensity exercise training can reduce the incidence of colds among postmenopausal women. These findings are of public health relevance and add a new facet to the growing literature on the health benefits of moderate exercise. The effect of exercise on salivary IgA levels and the incidence of upper respiratory tract infections in postmenopausal women. OBJECTIVES: To examine the patterns of upper respiratory tract infections (URTI) in postmenopausal Turkish women and the relationship of moderate aerobic exercise with secretion of salivary IgA and episodes of URTI. MATERIALS AND METHODS: Ninety healthy, sedentary women at ages 45 to 65 years volunteered to participate in a 12-week prospective study. They were randomized to three groups equal in number: indoor exercise, outdoor exercise, and no exercise. The exercising women were supervised during 30 min indoor treadmill walk or outdoor track walking sessions during 5 days/week at 60% of their calculated maximal heart rate. During a 12-week exercise program, episodes suggestive of URTI were recorded. Non-exercising women were followed with weekly telephone calls. The salivary IgA levels were measured in all the subjects before and at the end of the study. RESULTS: There were significant differences between the exercising and non-exercising women with respect to the number of URTI episodes and the length of URTI symptomatology per episode in favor of exercise. No significant difference was found between the indoor and outdoor exercising groups. The salivary IgA levels showed no significant differences between the three groups and within each group. CONCLUSION: Moderate intensity aerobic exercise is associated with fewer episodes of URTI and fewer days of URTI symptomatology per episode in healthy postmenopausal Turkish women, but this does not seem to be related to salivary IgA concentrations. Effect of moderate exercise on salivary immunoglobulin A and infection risk in humans. The incidence of upper respiratory tract infections (URTI) and salivary immunoglobulin A concentrations [IgA(s)] of nine individuals were examined during 12 weeks of moderate exercise training, and compared to ten sedentary controls. Changes in maximal oxygen uptake were assessed at initial, mid-point and final evaluations (T1-3), while changes in [IgA(s)] and salivary immunoglobulin concentration-salivary albumin concentration ratio ([IgA(s)]:[Alb(s)]) were monitored at T1 and T3. During the 12 week period, symptoms of URTI were self-recorded daily. During the period of training the level of fitness significantly increased ( P<0.05) in the exercise group. The number of days recording symptoms of influenza, but not of cold, and total light URTI symptoms was significantly reduced in the exercise group during the last weeks of training. A significant increase in [IgA(s)] and in [IgA(s)]:[Alb(s)] was found in the exercise group after training. Both [IgA(s)] and [IgA(s)]:[Alb(s)] were significantly related to the number of days showing symptoms of influenza ( P<0.01) and the total number of days of sickness ( P<0.05). These data provide quantitative support for the belief that regular, moderate exercise results in an increased [IgA(s)] at rest and [IgA(s)]:[Alb(s)], which may contribute to a decreased risk of infection. Assessment of immunological parameters following a qigong training program. BACKGROUND: Qigong is a type of Chinese psychosomatic exercise that integrates meditation, slow physical movements, and breathing, and to which numerous physical as well as mental benefits have been classically ascribed. The aim of the present study was to analyze the effects of a qigong program on various immunological parameters. MATERIAL/METHODS: 29 naive subjects participated in the study, of whom 16 were allocated to the experimental group and the rest to the control group. The experimental subjects underwent a qigong training program, conducted by a qualified instructor, consisting of half an hour of daily practice for one month. The day before the experiment commenced and the day after it finished, blood samples were drawn from all subjects for the quantification of immunological parameters (leukocytes, immunoglobulins, and complement). As statistical analysis, analysis of covariance (ANCOVA) was carried out. RESULTS: Statistically significant differences were found between the control and experimental groups, with the experimental group showing lower numbers of total leukocytes and eosinophils, number and percentage of monocytes, as well as complement C3 concentration. In addition, a similar result with a trend towards significance was observed in the number of eosinophils. CONCLUSIONS: These findings demonstrate that after one month of practicing qigong, significant immunological changes occurred between the experimental and control groups, with a consistently lower and broadly significant profile of these measures within the qigong practitioner group. The effects of moderate exercise training on natural killer cells and acute upper respiratory tract infections. A randomly controlled 15-wk exercise training (ET) study (five 45-min sessions/wk, brisk walking at 60% heart rate reserve) with a group of 36 mildly obese, sedentary women was conducted to investigate the relationship between improvement in cardiorespiratory fitness, changes in natural killer (NK) cell number and activity, and acute upper respiratory tract infection (URI) symptomatology. The study was conducted using a 2 (exercise and nonexercise groups) x 3 (baseline, 6-, and 15-wk testing sessions) factorial design, with data analyzed using repeated measures ANOVA. No significant change in NK cell number occurred as a result of ET as measured by the CD16 and Leu-19 monoclonal antibodies. ET did have a significant effect on NK cell activity (E:T 50:1) especially during the initial 6-wk period [F(2.68) = 12.34, p less than 0.001]. Using data from daily logs kept by each subject, the exercise group was found to have significantly fewer URI symptom days/incident than the nonexercise group (3.6 +/- 0.7 vs 7.0 +/- 1.4 days, respectively, p = 0.049). Improvement in cardiorespiratory fitness was correlated significantly with a reduction in URI symptom days/incident (r = 0.37, p = 0.025) and a change in NK cell activity from baseline to six but not 15 wks (r = 0.35, p = 0.036). In summary, moderate ET is associated with elevated NK cell activity after six but not 15 weeks, and reduced URI symptomatology in comparison to a randomized, sedentary control group. Physical activity and immune function in elderly women. The relationship between cardiorespiratory exercise, immune function, and upper respiratory tract infection (URTI) was studied in elderly women utilizing a randomized controlled experimental design with a follow-up of 12 wk. Thirty-two sedentary, elderly Caucasian women, 67-85 yr of age, who met specific selection criteria, were randomized to either a walking or calisthenic group; 30 completed the study. Twelve highly conditioned elderly women, 65-84 yr of age, who were active in endurance competitions, were recruited at baseline for cross-sectional comparisons. Intervention groups exercised 30-40 min, 5 d.wk-1, for 12 wk, with the walking group training at 60% heart rate reserve and the calisthenic group engaging in mild range-of-motion and flexibility movements that kept their heart rates close to resting levels. At baseline, the highly conditioned subjects exhibited superior NK (119 +/- 13 vs 77 +/- 8 lytic units, P < 0.01) and T (33.3 +/- 4.9 vs 21.4 +/- 2.1 cpm x 10(-3) using PHA, P < 0.05) cell function, despite no differences in circulating levels of lymphocyte subpopulations. Twelve weeks of moderate cardiorespiratory exercise improved the VO2max of the sedentary subjects 12.6%, but did not result in any improvement in NK cell activity or T cell function. Incidence of URTI was lowest in the highly conditioned group and highest in the calisthenic control group during the 12-wk study, with the walkers in an intermediate position (chi-square = 6.36, P = 0.042). In conclusion, the highly conditioned elderly women in this study had superior NK and T cell function when compared with their sedentary counterparts.(ABSTRACT TRUNCATED AT 250 WORDS) Immune response to exercise training and/or energy restriction in obese women. PURPOSE: The effect of exercise training (five 45-min walking sessions/wk at 60-75% maximum heart rate) and/or moderate energy restriction (4.19-5.44 MJ or 1,200-1,300 kcal x d(-1)) on innate and adaptive immunity (including mitogen-stimulated lymphocyte proliferation (MSLP), natural killer cell activity (NKCA), and monocyte and granulocyte phagocytosis and oxidative burst (MGPOB) was studied in obese women (N = 91, age 45.6 +/- 1.1 yr, body mass index 33.1 +/- 0.6 kg x m(-2)) randomized to one of four groups: control (C), exercise (E), diet (D), exercise, and diet (ED). METHODS: Aerobic power, body composition, and immune function were measured in all subjects before and after a 12-wk diet intervention period, with data analyzed using a 4 x 2 repeated measures design. All subjects self-reported symptoms of sickness in health logs using a precoded checklist. Statistical significance was set at P < or = 0.05. RESULTS: Data from this study indicate that although exercise training was unrelated to any significant changes in resting immune function, the number of days with symptoms of upper respiratory tract infection (URTI) was reduced relative to subjects in the nonexercise groups (5.6 +/- 0.9 and 9.4 +/- 1.1 sickness days, respectively, P < 0.05). Energy restriction and weight loss (7.9 +/- 0.7 kg) was associated with a significant decrease in MSLP, but no change in NKCA, MGPOB, or URTI. CONCLUSION: The data are consistent the viewpoint that weight loss, even at a moderate rate, is associated with a decrease in mitogen-stimulated lymphocyte proliferation without a change in various measures of innate immunity of the blood compartment. The impact of exercise training on the lipid peroxidation metabolomic profile and respiratory infection risk in older adults. UNLABELED: Aging is associated with oxidative stress that may increase susceptibility to respiratory infections (RIs). We aimed to assess the impact of exercise training on the risk of RIs in older adults and on a targeted metabolomic profile of stress oxidative lipid peroxidation-related metabolites. METHODS: In an 8-month clinical trial, 38 participants over 60 years of age were allocated to an exercise group (EG), in which participants underwent 90-min training sessions three times/week(n = 20), or a control group (CG), in which participants maintained daily physical activities(n = 18). Daily respiratory symptoms and RIs number and severity were collected. Serum by-products were assessed by comprehensive two-dimensional gas chromatography coupled to mass spectrometry with time of flight analyzer. Serum metabolomic profiling comprised 76 metabolites (alcohols, aldehydes, alkanes, and ketones). Principal components analysis and ANOVA-simultaneous component analysis were used to evaluate the metabolomic profile change. RESULTS: The odds ratio of RIs for the EG was 2.0 CI 95% [0.2;25]. The incidence of RIs was 47% [23;70] in the EG vs. 44%[12;77] in the CG. The metabolomic profiling showed that alkanes and aldehydes classes differed between the EG and the CG before and after intervention. A calibration model showed a relation between the metabolites from four main classes (ketones, alcohols, alkanes and aldehydes) and the prediction of the number of RIs. CONCLUSION: Moderate exercise training, in older adults, compared with no exercise in controls, did not show a difference in the risk of RIs. A pattern of lipid peroxidation was associated with the number of RIs. Effects of exercise on S-IGA and URS in postmenopausal women. 32 postmenopausal women were randomized to a 16-week home-based walking program or control group. Before and after the intervention, each subject completed a graded maximal treadmill test to establish VO(2)max and resting saliva was collected to determine levels of salivary immunoglobulin A. The 16-week walking program resulted in an increase in VO(2)max (+10.4%; p<0.01). Repeated measures ANOVA revealed a marked increase in the resting secretion rate of salivary immunoglobulin A (+37.4%; p<0.05) in the exercise group following training. Independent of study group, both before and after the intervention, the secretion rate of salivary immunoglobulin A ( - 32.3%) and saliva flow rate (- 29.3%) were reduced following acute maximal exercise (p<0.05). Weekly upper respiratory symptomatology logs revealed that the number of incidences of upper respiratory symptoms throughout the intervention period were the same and the duration per incidence (control: 5.3±1.5 days; exercise: 6.3±2.2 days) were similar between study groups. These findings in postmenopausal women support that the secretion rate of salivary immunoglobulin A and saliva flow rate are reduced immediately following maximal exercise. Moreover, a 16-week moderate intense walking program can increase the secretion of salivary immunoglobulin A without affecting upper respiratory symptomatology. The effect of exercise training on the severity and duration of a viral upper respiratory illness. PURPOSE: The purpose of this investigation was to determine whether exercise training affects the severity and duration of a rhinovirus-caused upper respiratory illness (URI). METHODS: Subjects who were rhinovirus 16 (RV 16) antibody-free completed a graded exercise test. Thirty-four individuals (ages 18-29 yr) of moderate fitness (32 mL.kg-1.min-1 to 60 mL.kg-1.min-1) were randomly assigned to the exercise group (EX) while 16 additional individuals of similar age and fitness served as a nonexercise (NEX) control group. All EX and NEX subjects were inoculated with RV 16 on 2 consecutive days. EX subjects completed 40 min of supervised exercise every other day at 70% of heart rate (HR) reserve for a 10-d period. Every 12 h, all subjects completed a 13-item symptom severity checklist and a physical activity log. Used facial tissues were collected and weighed (symptom severity measure) during these same reporting periods. RESULTS: A two group by nine measure (2 x 9) repeated measures ANOVA procedure showed no difference in symptom questionnaire mean scores and the mucous weights of the EX and NEX groups for days 2-10 of the experiment. A two measure by five measure (2 x 5) repeated measures ANOVA procedure indicated no differences between the pre- and post-exercise questionnaire means for the five sessions that EX subjects exercised. Statistical significance was set at P < 0.05. CONCLUSION: These results suggest that moderate exercise training during a rhinovirus-caused URI under the conditions of this study design do not alter the severity and duration of the illness. Effect of exercise on upper respiratory tract infection in sedentary subjects. OBJECTIVE: To determine if exercise training affects the severity and duration of a naturally acquired upper respiratory tract infection (URTI) in sedentary subjects. METHODS: Subjects were sedentary volunteers (two or fewer days a week of exercise for less than 30 minutes a day for the previous three months), 18-29 years of age, with a naturally acquired URTI (three to four days of onset). All subjects were screened-for example, asthma, hay fever-by a doctor and were afebrile. Volunteers were alternately assigned to an exercise (EX) group (four men, seven women) or a non-exercise (NEX) group (three men, eight women). Subjects in the EX group completed 30 minutes of supervised exercise at 70% of target heart rate range for five days of a seven day period. For the initial screening, and every 12 hours, all subjects completed a 13 item symptom severity checklist and a physical activity log. Cold symptom scores were obtained until the subjects were asymptomatic. Significance was set at p</=0.05. RESULTS: There were no significant differences between EX and NEX group mean symptom scores for the morning and evening reporting periods. There were also no differences between the groups for the mean number of days from the baseline symptom score to when the subjects were asymptomatic. There were no differences between physical activity levels, other than what was assigned in the EX group. CONCLUSION: Moderate exercise in sedentary subjects with naturally acquired URTI probably does not alter the overall severity and duration of the illness. Previously sedentary people who have acquired a URTI and have just initiated an exercise programme may continue to exercise. Options: A: Exercise significantly reduced the number of ARI episodes per person per year. B: Exercise significantly reduced the proportion of participants experiencing at least one ARI during the study period. C: Exercise significantly reduced the severity of ARI symptoms and the number of symptom days during the follow-up period. D: Exercise had no significant effect on the severity of ARI symptoms or the number of symptom days during the follow-up period.	C
4,619	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What are the conclusions regarding the effectiveness of treatments for stuttering and fulminant priapism in individuals with sickle cell disease? Please answer this question based on the information provided below: Randomized controlled trial of sildenafil for preventing recurrent ischemic priapism in sickle cell disease. BACKGROUND: Successful preventive therapy for ischemic priapism, a disorder of penile erection with major physical and psychologic consequences, is limited. We conducted a randomized, double-blind, placebo-controlled clinical trial to assess the efficacy and safety of sildenafil by a systematic dosing protocol to prevent recurrent ischemic priapism associated with sickle cell disease. METHODS: Thirteen patients with sickle cell disease reporting priapism recurrences at least twice weekly were randomized to receive sildenafil 50 mg or placebo daily, unassociated with sleep or sexual activity, for 8 weeks, followed by open-label use of this sildenafil regimen for an additional 8 weeks. RESULTS: Priapism frequency reduction by 50% did not differ between sildenafil and placebo groups by intention-to-treat or per protocol analyses (P = 1.0). However, during open-label assessment, 5 of 8 patients (62.5%) by intention-to-treat analysis and 2 of 3 patients (66.7%) by per protocol analysis met this primary efficacy outcome. No significant differences were found between study groups in rates of adverse effects, although major priapism episodes were decreased 4-fold in patients monitored "on-treatment." CONCLUSIONS: Sildenafil use by systematic dosing may offer a strategy to prevent recurrent ischemic priapism in patients with sickle cell disease. Prevention of Ischemic Priapism in Sickle Cell Disease: Sildenafil: Commentary on: Randomized Controlled Trial of Sildenafil for Preventing Recurrent Ischemic Priapism in Sickle Cell Disease. A prospective diary study of stuttering priapism in adolescents and young men with sickle cell anemia: report of an international randomized control trial--the priapism in sickle cell study. Priapism is defined as a prolonged, persistent, and purposeless penile erection. It is a common (35%) but frequently understated complication in young men and adults with sickle cell disease. We had previously demonstrated an association between stuttering attacks (<4 hours) and an acute catastrophic event with its consequent problems of erectile dysfunction and impotence. We describe a randomized, placebo-controlled, clinical study looking at medical prophylaxis with 2 oral α-adrenergic agonists, etilefrine and ephedrine, in preventing stuttering attacks of priapism. One hundred thirty-one patients were registered into a 2-phase (observational and intervention phase) study, and 86 patients (66%) completed Phase A diary charts. Forty-six patients (59%) completed a 6-month treatment phase (Phase B), and the remaining patients were lost to follow-up despite persistent efforts to contact them. Various reasons are postulated for the high attrition rates. The drugs were well tolerated, and no serious adverse events were reported. There was no significant difference among the 4 treatment groups in the weekly total number of attacks in Phase B (analysis of covariance P = .99) nor among the average pain score per attack after adjusting for attack rates and pain scores in Phase A (analysis of covariance P = .33). None of the patients who completed the study required penile aspiration at study sites while on medical prophylaxis. Young men with sickle cell disease are not comfortable engaging with health care providers about issues relating to their sexual health. The full impact of an improved awareness campaign and early presentation to hospital merits further standardized study. Priapism still contributes seriously to the comorbidity experienced by this previously inaccessible group of patients and medical prophylaxis with oral α-adrenergic agonists is feasible. Future international collaborative efforts using some of the lessons learnt in this study should be undertaken. Re.: A prospective diary study of stuttering priapism in adolescents and young men with sickle cell anemia: report of an international randomized control trial; the Priapism in Sickle Cell Study (PISCES study). Stilboestrol and stuttering priapism in homozygous sickle-cell disease. A double-blind, placebo-controlled crossover study was conducted in 11 patients with stuttering attacks of priapism and homozygous sickle-cell (SS) disease. Stilboestrol 5 mg daily was better than the placebo in preventing attacks. Options: A: There is strong evidence supporting the effectiveness of stilboestrol, etilefrine, and ephedrine in reducing the frequency of stuttering priapism. B: Sildenafil has been proven to significantly reduce the frequency of stuttering priapism and has minimal side effects. C: There is a lack of evidence for the benefits or risks of the different treatments for both stuttering and fulminant priapism in sickle cell disease. D: All treatments studied (stilboestrol, etilefrine, ephedrine, and sildenafil) have been shown to be effective in reducing the frequency of stuttering priapism with high certainty.	C
4,620	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What are the comparative outcomes of using a mechanical microkeratome versus a femtosecond laser in LASIK for adults with myopia or myopic astigmatism? Please answer this question based on the information provided below: Comparison of corneal aberration changes after laser in situ keratomileusis performed with mechanical microkeratome and IntraLase femtosecond laser: 1-year follow-up. PURPOSE: To compare corneal aberration changes 1 year after myopic laser in situ keratomileusis (LASIK) performed with a mechanical microkeratome and IntraLase femtosecond laser. METHODS: Twenty four eyes of 15 patients underwent LASIK with the Hansatome microkeratome, and 23 eyes of 13 patients underwent LASIK with the IntraLase femtosecond laser. A standard ablation was performed with the Bausch & Lomb Technolas 217 excimer laser. Topography data were used to calculate corneal aberrations with a 3.0 mm and 5.00 mm pupil, before and 12 months after surgery. The increasing factor (IF), defined as the ratio between the postoperative and preoperative mean value of the optical aberration, was calculated. The method of Mulhern et al was used to evaluate the centration of ablation. The comalike aberration was correlated with the decentration of ablation. The Student t test was used for the statistical anaylsis. RESULTS: The postoperative mean decentration of ablation was <0.5 mm. The comalike aberration appeared to be positively correlated with the decentration of ablation in both groups with a 5.0-mm pupil (P < 0.05). With a 3.00-mm pupil, the comalike aberration changed in the Hansatome group, whereas with a 5.00-mm pupil, all aberrations statistically significantly changed in both groups (P < 0.05). The IF similarly increased in 2 groups for spherical-like aberration, whereas IF greatly increased for total and comalike aberrations in the Hansatome group. CONCLUSIONS: Wavefront corneal aberrations change significantly 1 year after myopic LASIK performed with the Hansatome microkeratome as well as with IntraLase femtosecond lasers. Both of the procedures induce higher-order aberrations in the anterior corneal surface, but the amount of comalike aberration increases more with the Hansatome mechanical microkeratome. Femtosecond laser versus mechanical keratome flaps in wavefront-guided laser in situ keratomileusis: prospective contralateral eye study. PURPOSE: To compare the outcomes of wavefront-guided laser in situ keratomileusis (LASIK) performed using the IntraLase femtosecond laser with the outcomes using the Hansatome mechanical microkeratome. SETTING: Private clinic, Overland Park, Kansas, USA. METHODS: In a prospective contralateral-eye study performed under institutional review board supervision, 51 consecutive patients (102 eyes) had bilateral wavefront-guided LASIK for myopia using the Alcon LADARVision laser. One eye of each patient was randomized to have the flap created with the IntraLase femtosecond laser and the other flap using a standard compression head Hansatome microkeratome. All other treatment parameters were the same. RESULTS: The IntraLase group had significantly better mean uncorrected visual acuity (UCVA) at all intervals from 1 day to 3 months postoperatively. The mean spheroequivalent at 3 months was more myopic with the Hansatome (-0.34 diopter [D] +/- 0.28 [SD]) than with the IntraLase (-0.19 +/- 0.24 D) (P<.01). The mean residual astigmatism at 3 months was also significantly higher in the Hansatome group than in the IntraLase group (0.32 +/- 0.25 D and 0.17 +/- 0.20 D, respectively) (P<.01). The differences in UCVA persisted after spheroequivalent outcomes were controlled for but equilibrated when the analysis was modified to control for manifest postoperative astigmatism. Aberrometry showed significantly higher astigmatism and trefoil in the Hansatome group. Recovery of corneal sensation and epithelial integrity was similar between groups. CONCLUSIONS: The statistically better UCVA and manifest refractive outcomes after LASIK with the IntraLase femtosecond laser may be the result of differences in postoperative astigmatism and trefoil. These findings are consistent with previous findings of better astigmatic outcomes with the IntraLase laser and may have clinical significance for wavefront-guided treatments. [Femtosecond laser versus mechanical microkeratome for LASIK flap creation]. PURPOSE: To assess LASIK flaps made by femtosecond laser and mechanical microkeratome. METHODS: Clinical, prospective, randomized, masked study of 32 eyes (16 patients). Both eyes of all patients were operated, each patient underwent different techniques for lasik. Microkeratome Hansatome (TM) Bausch & Lomb (group microkeratome) was used in one eye and femtosecond laser Femto LDV(TM) Ziemer (group femtosecond) was used for the fellow eye. Patients were selected from the Refractive Surgery service of the Eye Hospital of Paraná between July 2010 and September 2010. Inclusion criteria were myopia less than 6.00 D, astigmatism less than 3.00 D, hyperopia less than 5.00 D, stable refraction over one year, corneal diameter smaller than 11 mm, discontinuation of contact lenses seven days before the preoperative evaluation, corrected visual acuity of at least 20/20. Eyes were randomly allocated for each technique. The studied variables were: visual acuity with and without correction, residual refractive error, high order aberrations, low contrast visual acuity, complications and subjective patient preference. RESULTS: All studied variables were similar between the two groups. CONCLUSION: We could not demonstrate any difference between the studied groups. Comparison of the femtosecond laser and mechanical keratome for laser in situ keratomileusis. OBJECTIVE: To compare clinical outcomes between fellow eyes randomized to femtosecond laser-created flaps (femtosecond group) or mechanical keratome-created flaps (mechanical group) during wavefront-guided laser in situ keratomileusis. DESIGN: Prospective, randomized, comparative clinical study. MAIN OUTCOME MEASURES: Efficacy, safety, predictability, stability, changes in corneal optical aberrations, and low-contrast visual acuity before and 1 week and 1, 3, 6, and 12 months after surgery. RESULTS: Forty-three patients underwent evaluation in this study. One month after surgery, the mean (SD) spherical equivalent was -0.15 (0.30) diopters (D) for the femtosecond group and -0.12 (0.29) D for the mechanical group (differences were not statistically significant). Twelve months after surgery, 39 eyes (98%) in the femtosecond group had uncorrected visual acuity of 20/20 or better compared with 37 (95%) in the mechanical group. The femtosecond group had fewer high-order, spherical, and coma aberrations and more trefoil aberrations than the mechanical group at 1 month (P = .55), 3 months (P = .05), 6 months (P = .33), and 12 months (P = .48) after surgery. At 25% contrast, the femtosecond group had gains at 1 month (P = .01) and 6 months (P = .008) after surgery. CONCLUSION: Twelve months after keratomileusis, clinical outcomes were similar for both groups. Dry eye after laser in situ keratomileusis with femtosecond laser and mechanical keratome. PURPOSE: To prospectively compare dry-eye symptoms after laser in situ keratomileusis (LASIK) with mechanical keratome-created flaps and femtosecond laser keratome-created flaps. SETTING: Department of Ophthalmology, Stanford University School of Medicine, Stanford, California, USA. DESIGN: Randomized clinical trial. METHODS: Fellow eyes were prospectively randomized to the mechanical keratome group and femtosecond laser keratome group. Patients had wavefront-guided LASIK using a mechanical keratome in 1 eye and a femtosecond laser keratome in the fellow eye. They completed dry-eye questionnaires preoperatively and 1, 3, 6, and 12 months postoperatively. The effect of laser ablation depth, sex, age, and flap thickness on dry-eye symptoms was also analyzed. RESULTS: The study enrolled 51 patients. There was no statistically significant change in dry-eye symptoms except in the femtosecond group 1 month postoperatively (mean increase 1.08) (P=.03). There were no significant differences in symptoms between the 2 groups (P=.7). The dry-eye score was 1.3 points lower in women than in men (P=.01). Central ablation depth, flap thickness, and age did not significantly affect the reported dryness. CONCLUSION: There appeared to be no statistically significant difference in self-reported dry-eye symptoms between the mechanical keratome group and the femtosecond laser keratome group. Corneal aberrations and visual acuity after laser in situ keratomileusis: femtosecond laser versus mechanical microkeratome. PURPOSE: To compare corneal high-order aberrations and visual acuity after laser in situ keratomileusis (LASIK) with the flap created by a femtosecond laser (bladeless) to LASIK with the flap created by a mechanical microkeratome. DESIGN: Prospective, randomized, paired-eye study. METHODS: Fellow eyes of 21 patients with myopia or myopic astigmatism were randomized by ocular dominance. Corneal topography and visual acuity were measured before and at 1, 3, 6, 12, and 36 months after LASIK. Wavefront errors from the anterior corneal surface were calculated from the topography data over 4- and 6-mm-diameter pupils and decomposed into Zernike polynomials to the 6th order. RESULTS: There were no differences in corneal total high-order aberrations, spherical aberration, coma, or trefoil between methods of flap creation at any examination over 4- and 6-mm-diameter pupils. Over a 6-mm pupil, total high-order aberrations increased by 1 month after LASIK with both treatments (P <or= .001) and remained increased through 36 months (P <or= .001). Uncorrected and best-corrected visual acuity did not differ between methods at any examination and remained stable postoperatively through 3 years; the minimum detectable difference in visual acuity between treatments was <or=0.1 logMAR (<or=1 line of vision, alpha = 0.05/6, beta = 0.20, n = 21). CONCLUSIONS: The planar configuration of the femtosecond laser flap did not offer any advantage in corneal high-order aberrations or visual acuity through 3 years after LASIK. Corneal high-order aberrations remain stable through 3 years after LASIK. Corneal endothelial cell changes 5 years after laser in situ keratomileusis: femtosecond laser versus mechanical microkeratome. PURPOSE: To compare corneal endothelial cell density (ECD) and morphology between flap creation with a femtosecond laser and flap creation with a mechanical microkeratome 5 years after laser in situ keratomileusis (LASIK). SETTING: Mayo Clinic, Rochester, Minnesota, USA. DESIGN: Prospective randomized masked paired-eye study. METHODS: In this study of LASIK for myopia or myopic astigmatism, fellow eyes were randomized by ocular dominance to flap creation by a femtosecond laser or by a mechanical microkeratome. Central endothelial images were analyzed before and 3 years and 5 years after LASIK; endothelial cell variables were compared between treatments at each examination. Relationships between endothelial cell loss and contact lens wear, residual bed thickness, and preoperative refractive error were evaluated. RESULTS: There were no differences in the ECD, percentage of hexagonal cells, or coefficient of variation of cell area between treatments at any examination (all P = .99); the smallest detectable differences were 120 cells/mm(2), 5%, and 2%, respectively. The mean annual rate of corneal endothelial cell loss was -0.1% ± 1.2% (SD) and -0.1% ± 1.0% for the femtosecond laser and the mechanical microkeratome, respectively. Endothelial cell loss was not associated with contact lens wear, residual bed thickness, or preoperative refractive error. CONCLUSIONS: The energy delivered to the cornea during femtosecond laser flap creation did not affect the corneal endothelium 5 years after LASIK when compared with flap creation with a mechanical microkeratome. Corneas that have had either method of flap creation could be accepted as donor tissue for endothelial keratoplasty from the standpoint of endothelial health. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. Changes in Keratocyte Density and Visual Function Five Years After Laser In Situ Keratomileusis: Femtosecond Laser Versus Mechanical Microkeratome. PURPOSE: To determine the effects of keratocyte loss on optical properties and vision after laser in situ keratomileusis (LASIK) with the flap created with a femtosecond laser or a mechanical microkeratome. DESIGN: Randomized clinical paired-eye study. METHODS: Both eyes of 21 patients received LASIK for myopia or myopic astigmatism. One eye of each patient was randomized by ocular dominance to flap creation with a femtosecond laser and the other eye to flap creation with a mechanical microkeratome. Before LASIK and at 1, 3, and 6 months and 1, 3, and 5 years after LASIK, keratocyte density was measured using confocal microscopy, and high-contrast visual acuity and anterior corneal wavefront aberrations were measured by standard methods. At each visit, all variables were compared between methods of creating the flap and to the same variable before treatment using paired tests with Bonferroni correction for multiple comparisons. RESULTS: Keratocyte density in the flap decreased by 20% during the first year after LASIK and remained low through 5 years (P < .001). High-order wavefront aberrations increased and uncorrected visual acuity improved immediately after surgery, but these variables did not change further to 5 years. There were no differences in any variables between treatments. CONCLUSIONS: A sustained reduction in keratocyte density does not affect vision or optical properties of the cornea through 5 years after LASIK. The method of creating a LASIK flap does not influence the changes in keratocyte density in the flap. Femtosecond laser versus mechanical microkeratome for LASIK: a randomized controlled study. PURPOSE: To compare corneal haze (backscattered light) and visual outcomes between fellow eyes randomized to LASIK with the flap created by a femtosecond laser (bladeless) or with the flap created by a mechanical microkeratome. DESIGN: Randomized, controlled, paired-eye study. PARTICIPANTS: Twenty-one patients (42 eyes) received LASIK for myopia or myopic astigmatism. METHODS: One eye of each patient was randomized to flap creation with a femtosecond laser (IntraLase FS, IntraLase Corp., Irvine, CA) with intended thickness of 120 microm, and the fellow eye to flap creation with a mechanical microkeratome (Hansatome, Bausch & Lomb, Rochester, NY) with intended thickness of 180 microm. Patients were examined before and at 1, 3, and 6 months after LASIK. MAIN OUTCOME MEASURES: Corneal backscatter, high-contrast visual acuity, manifest refractive error, contrast sensitivity, and intraocular forward light scatter were measured at each examination. Flap thickness was measured by confocal microscopy at 1 month, and patients were asked if they preferred the vision in either eye at 3 months. RESULTS: Corneal backscatter was 6% higher after bladeless LASIK than after LASIK with the mechanical microkeratome at 1 month (P = 0.007), but not at 3 or 6 months. High-contrast visual acuity, contrast sensitivity, and forward light scatter did not differ between treatments at any examination. Flap thicknesses at 1 month were 143+/-16 microm (bladeless, mean +/- standard deviation) and 138+/-22 microm (mechanical microkeratome), with no statistical difference in variances. At 3 months, 5 patients preferred the bladeless eye, 7 patients preferred the microkeratome eye, and 9 patients had no preference. CONCLUSIONS: The method of flap creation did not affect visual outcomes during the first 6 months after LASIK. Although corneal backscatter was greater early after bladeless LASIK than LASIK with the mechanical microkeratome, patients did not perceive a difference in vision. Subbasal nerve density and corneal sensitivity after laser in situ keratomileusis: femtosecond laser vs mechanical microkeratome. OBJECTIVE: To compare changes in subbasal nerve density and corneal sensitivity after laser in situ keratomileusis (LASIK) with the flap created by a femtosecond laser (bladeless) vs a mechanical microkeratome. DESIGN: In a randomized paired-eye study, 21 patients received myopic LASIK with the flap created by a femtosecond laser in one eye and by a mechanical microkeratome in the fellow eye. Eyes were examined before and at 1, 3, 6, 12, and 36 months after LASIK. Central subbasal nerve density was measured by using confocal microscopy. Corneal mechanical sensitivity was measured by using a gas esthesiometer and was expressed as the ratio of mechanical threshold in eyes that received LASIK to mechanical threshold in concurrent control eyes. RESULTS: Subbasal nerve density and corneal sensitivity did not differ between methods of flap creation at any examination. Mean (SD) nerve density was decreased at 1 month (bladeless, 974 [2453] μm/mm(2); microkeratome, 1308 [2881] μm/mm(2)) compared with the preoperative examination (bladeless, 10,883 [5083] μm/mm(2), P < .001; microkeratome, 12,464 [6683] μm/mm(2), P < .001) and remained decreased through 12 months (P < .001). Mechanical threshold ratios did not differ from that at the preoperative examination through 36 months for either LASIK treatment; when all LASIK eyes were combined, the mechanical threshold ratio was transiently higher (decreased sensitivity) at 1 month (1.29 [0.85]) compared with the preoperative examination (0.89 [0.73], P = .05). CONCLUSIONS: The planar configuration of the femtosecond laser flaps is not associated with faster reinnervation compared with the microkeratome flaps. The prolonged decrease in subbasal nerve density after LASIK is not accompanied by a prolonged decrease in corneal sensitivity. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00350246. Dry eye associated with laser in situ keratomileusis: Mechanical microkeratome versus femtosecond laser. PURPOSE: To compare the incidence of laser in situ keratomileusis (LASIK)-associated dry eye and the need for postoperative cyclosporine A treatment after flap creation with a femtosecond laser and a mechanical microkeratome. SETTING: Cole Eye Institute, Cleveland, Ohio, USA. METHODS: Eyes were randomized to flap creation with an IntraLase femtosecond laser (30 or 60 kHz) or a Hansatome microkeratome. No patient had signs, symptoms, or treatment of dry eye preoperatively. Flap thickness was determined by intraoperative ultrasonic pachymetry. Slitlamp assessments of the cornea and need for postoperative dry-eye treatment were evaluated preoperatively and 1 month postoperatively. RESULTS: The flap was created with the femtosecond laser in 113 eyes and with the microkeratome in 70 eyes. The difference in mean central flap thickness between the femtosecond group (111 mum +/- 14 [SD]) and the microkeratome group (131 +/- 25 mum) was statistically significant (P<.001). The incidence of LASIK-associated dry eye was statistically significantly higher in the microkeratome group (46%) than in the femtosecond group (8%) (P<.0001), as was the need for postoperative cyclosporine A treatment (24% and 7%, respectively) (P<.01). In the microkeratome group, there was no correlation between thick flaps and a higher incidence of LASIK-induced dry eye. CONCLUSIONS: Eyes with femtosecond flaps had a lower incidence of LASIK-associated dry eye and required less treatment for the disorder. In addition to neurotrophic effects from corneal nerve cutting, other factors may be important because no correlation was found between flap thickness (or ablation depth) and the incidence of LASIK-induced dry eye. Visual experiences during different stages of LASIK: Zyoptix XP microkeratome vs Intralase femtosecond laser. PURPOSE: To describe the loss of light perception and other visual experiences encountered during different stages of laser in situ keratomileusis (LASIK) and to compare patients' experiences between LASIK performed with the Zyoptix XP microkeratome and Intralase laser. DESIGN: Prospective, randomized, self-matched clinical study. METHODS: Forty-one patients (82 eyes) had bilateral LASIK with the corneal flap fashioned by Zyoptix XP microkeratome in one eye and Intralase laser in the other. They were interviewed postoperatively with a standardized questionnaire about their intraoperative visual experiences, including light perception and ability to see the red fixation light. RESULTS: During both vacuum suction and corneal flap fashioning, a higher proportion of eyes in the Zyoptix XP microkeratome group lost light perception compared with the Intralase group (85.4% vs 39.0% and 90.2% vs 61.0%; P < .001 and P = .004, respectively). Patients also saw flashes, various colors, movement, the surgeon's hands or fingers, and the surgeon during surgery, and there was no difference in these visual experiences between the Zyoptix XP microkeratome and Intralase groups. Overall, eight (19.5%) of 41 patients were frightened by their intraoperative visual experiences during LASIK. CONCLUSIONS: Patients retain light perception during most stages of LASIK except during suction and fashioning of the corneal flap, when some are temporarily unable to see. Many also experience various visual sensations intraoperatively, and 19.5% of patients are frightened by their visual experiences. Randomized prospective clinical study comparing induced aberrations with IntraLase and Hansatome flap creation in fellow eyes: potential impact on wavefront-guided laser in situ keratomileusis. PURPOSE: To measure and compare the changes in objective wavefront aberration and subjective manifest refraction after laser in situ keratomileusis (LASIK) flap creation with a mechanical microkeratome and a femtosecond laser. SETTING: Private practice refractive surgery center, Irvine, California, USA. METHODS: This randomized prospective study comprised 9 patients (18 eyes) treated with a 2-step LASIK procedure: lamellar keratectomy with a Hansatome microkeratome (Bausch & Lomb) or the IntraLase femtosecond laser in fellow eyes followed by non-wavefront-guided (standard) excimer laser treatment with the Technolas 217A (Bausch & Lomb) excimer laser 10 weeks later. Fellow eyes were matched to within 0.75 diopter (D) sphere and 0.50 D cylinder. Patients were followed for 3 months after excimer laser treatment. Preoperative and post-flap creation wavefront aberrometry using a Hartmann-Shack aberrometer and manifest refraction were compared between the 2 groups. The same tests were performed 3 months after excimer laser ablation. RESULTS: Statistically significant changes were seen in defocus wavefront aberrations after Hansatome (P=.004) and IntraLase (P=.008) flap creation. A hyperopic shift in manifest refraction was noted in the Hansatome group after the creation of the corneal flap (P=.04); no statistically significant changes in manifest refraction were seen in the IntraLase group. Statistically significant changes in total higher-order aberrations (HOAs) (trefoil and quadrafoil Zernike terms) were seen after flap creation in the Hansatome group (P=.02). No significant changes in HOAs were noted after flap creation in the IntraLase group. After the flap was relifted and standard excimer laser ablation was performed, a statistically significant increase in coma occurred in the Hansatome group (P=.008). Standard refractive outcomes in the 2 groups were similar. CONCLUSIONS: The creation of the LASIK flap alone can modify the eye's optical characteristics in low-order aberrations and HOAs. A significant increase in HOAs was seen in the Hansatome group but not in the IntraLase group. This may have significant clinical implications in wavefront-guided LASIK treatments, which are based on measurements made before flap creation. Comparison of the flaps made by femtosecond laser and automated keratomes for sub-bowman keratomileusis. BACKGROUND: Thin-flap laser in situ keratomileusis (LASIK) is the new trend of refractive error correction surgery, the formation of corneal flap is crucial for a success of LASIK surgery. This study aimed to assess and compare the variations of LASIK flap created by the IntraLase femtosecond laser, Moria One Use-Plus SBK and Moria M2 Single-Use 90 µm-head microkeratome using Anterior segment optical coherence tomography (Visante OCT). METHODS: One hundred and sixty-one eyes of 81 consecutive patients were enrolled in this prospective study and randomly divided into three groups depending on the flap creation method: flap creation with the the IntraLase femtosecond laser (IntraLase group, 59 eyes), flap creation with the Moria One Use-Plus SBK (SBK group, 44 eyes), and flap creation with the Moria M2 Single-Use 90 µm-head microkeratome (M2SU90 group, 58 eyes). The nominal flap thickness was 110 µm for all patients and for the three devices. One month after surgery, Visante OCT was used to measure the flap thickness at 20 locations on each cornea and the results were assessed for uniformity, regularity, and accuracy. RESULTS: At 1 month after surgery, the mean central flap thickness was (111 ± 3) µm in the IntraLase group, (114 ± 8) µm in the SBK group, and (118 ± 13) µm in the M2SU90 group respectively. The flaps in the IntraLase group and the SBK group were more regular, showing an almost planar configuration, than the meniscus-shaped flaps in the M2SU90 group. The maximum deviation from the intended flap thickness (110 µm) was 6 µm in the IntraLase group, 10 µm in the SBK group, and 20 µm in the M2SU90 group respectively. A difference greater than 20 µm was observed in 0.42% of measurements in the IntraLase group; 2.95% of the measurements in the SBK group and 21.12% of measurements in the M2SU90 group. CONCLUSIONS: The flaps created by the IntraLase femtosecond laser and Moria One Use-Plus SBK are more uniform; more regular, and more accurate than those created by the Moria M2 Single-Use 90 µm-head microkeratome. The first two methods can make precise flaps for Sub-Bowman Keratomileusis. Comparison of the Ziemer FEMTO LDV femtosecond laser and Moria M2 mechanical microkeratome. PURPOSE: To assess and compare the dimensions of LASIK flaps created by the Ziemer FEMTO LDV "Classic" femtosecond (FS) laser and Moria M2 microkeratome with 110-μm head and -20 blade. METHODS: Seven hundred twenty eyes from 360 consecutive patients were enrolled in this study and divided into two groups of equal size for flap creation with the Ziemer LDV (FS laser group) and Moria M2 mechanical microkeratome (microkeratome group). Nominal flap thickness was 110 μm for all patients and for both devices. Flap thickness was measured by Fourier-domain optical coherence tomography in 14 specified positions on each flap 1 week after surgery to analyze the regularity, uniformity, and accuracy of the two types of LASIK flaps. RESULTS: The mean deviation between achieved and attempted flap thickness was smaller in the FS laser group than in the microkeratome group. The flaps in the FS laser group were more regular and uniform, showing an almost planar configuration, whereas flaps in the microkeratome group had a meniscus shape and were significantly thicker near the flap edge. Nasal and temporal flap thickness did not differ significantly in the FS laser group, whereas in the microkeratome group, characteristic differences in temporal versus nasal flap thickness were noticed. Within the 5040 individual measurements of the 360 eyes, deviations of >20 μm were observed in 0.73% of eyes in the FS laser group and 42.4% in the microkeratome group. CONCLUSIONS: The dimensions of flaps created by the Ziemer LDV femtosecond laser were more uniform and accurate than those created by the Moria M2 microkeratome. Options: A: There is a significant difference in visual acuity outcomes between the two methods. B: Mechanical microkeratome is associated with a higher risk of diffuse lamellar keratitis compared to femtosecond laser. C: Femtosecond laser is associated with a higher risk of dry eye compared to mechanical microkeratome. D: There is no significant difference in visual acuity outcomes between the two methods.	D
4,621	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What were the findings regarding the timing of parenteral nutrition (PN) in critically ill term and late preterm infants in terms of in-hospital all-cause mortality and neonatal mortality? Please answer this question based on the information provided below: Randomized, controlled trial of early intravenous nutrition for prevention of neonatal jaundice in term and near-term neonates. BACKGROUND: This study was undertaken to investigate the effects of early parenteral nutrition on prevention of neonatal jaundice in term and near-term neonates who could not be enterally fed. PATIENTS AND METHODS: Seventy-two infants were randomized into 2 groups: the early parenteral nutrition group (group 1) received 1.0 g/kg/d amino acids beginning within the first day and 1.0 g/kg/d lipid added the next day. The conventional nutrition group (group 2) started on a solution containing 10% glucose and electrolytes in the first 72 hours of life, followed by 0.5 g/kg/d amino acids and lipid. Amino acids and lipid were each increased by 0.5 g/kg/d to a maximum of 3.0 g/kg/d in both groups. Main outcome measures were energy intake; serum bilirubin levels at 24, 48, and 72 hours; need for phototherapy; and duration of phototherapy. RESULTS: Higher energy intake was achieved after the first day in group 1. Daily serum bilirubin levels did not significantly differ between groups. Nine patients in each group required phototherapy. The initiation times of phototherapy were 92.9 hours +/- 25.5 in group 1 and 83.1 hours +/- 28.5 in group 2. Durations of phototherapy were 37.3 hours +/- 11.1 in group 1 and 52.0 hours +/- 20.7 in group 2. There were no significant differences in the requirement, initiation time, and duration of phototherapy. CONCLUSIONS: Early parenteral nutrition has no proven benefit in terms of therapy requirement or severity and duration of neonatal jaundice compared with conventional parenteral nutrition in term and near-term infants who could not be enterally fed. Early versus late parenteral nutrition in critically ill, term neonates: a preplanned secondary subgroup analysis of the PEPaNIC multicentre, randomised controlled trial. BACKGROUND: Previous randomised studies showed that withholding parenteral nutrition for 1 week of critical illness was superior to early initiation (<24-48 h) of parenteral nutrition in children and adults. However, neonates are considered more susceptible to macronutrient deficits. We investigated the effect of withholding parenteral nutrition for 1 week in critically ill, term neonates. METHODS: We previously did a randomised, controlled study (PEPaNIC) of children aged up to 17 years admitted to paediatric intensive-care units (ICUs) in three hospitals in Belgium, Canada, and the Netherlands randomly assigned (1:1) to either standard care of parenteral nutrition initiated early within 24 h of admission to an ICU or late parenteral nutrition (where supplemental parenteral nutrition was withheld for 1 week after admission to the ICU). In this preplanned, secondary subanalysis of PEPaNIC, we looked at data from critically ill, term neonate participants (gestational age ≥37 weeks) aged up to 28 days (studied in overlapping age groups of ≤4 weeks, ≤1 week, and <1 day-ie, age at admission). In both the early parenteral nutrition and late parenteral nutrition groups, enteral nutrition was initiated as soon as possible and increased according to local protocols. Outcome assessors and investigators not directly involved in the paediatric ICU were not informed of treatment allocation. The primary endpoints were incidence of new infections and duration of paediatric ICU dependency (quantified as the number of days in the paediatric ICU and likelihood of earlier live discharge from the ICU), analysed based on intention to treat. Multivariable analyses were adjusted for the following risk factors: centre, Paediatric Logistic Organ Dysfunction score, Paediatric Index of Mortality 2 score, diagnosis group, and weight-for-age Z scores on admission. Secondary safety outcomes were mortality (at 90 days, during the intervention, in the paediatric ICU, and in the hospital) and hypoglycaemic incidents during the intervention. All patients in the respective groups were included in the safety analysis. FINDINGS: Between June 18, 2012, and July 27, 2015, we included 209 participants in this substudy, 145 of whom were aged up to and including 1 week and 45 aged younger than 1 day. In neonates aged up to and including 4 weeks, late parenteral nutrition increased the likelihood of earlier live discharge from the paediatric ICU compared with early parenteral nutrition (adjusted hazard ratio [HR] 1·61, 95% CI 1·19-2·20; p=0·0021) but did not affect the risk of infection. The risk of infection in neonates aged up to and including 1 week and younger than 1 day was lower with late parenteral nutrition than with early parenteral nutrition (adjusted odds ratios [OR] 0·36, 95% CI 0·15-0·83, p=0·017; and 0·10, 0·01-0·64, p=0·015, respectively). For neonates aged up to and including 1 week, the likelihood of an earlier live discharge from the ICU was higher with late parenteral nutrition (adjusted HR 1·69, 95% CI 1·16-2·46; p=0·0063). For neonates younger than 1 day, adjusted HR was 1·95 (95% CI 0·93-4·12; p=0·078). Mortality at all studied timepoints was similar between the groups for all ages; however, in neonates aged up to and including 4 weeks and aged up to and including 1 week, the risk of hypoglycaemia was higher with late parenteral nutrition (23% vs 14%; adjusted OR 3·05, 95% CI 1·27-7·35, p=0·013; and 24% vs 14%; 3·57, 1·23-10·45, p=0·019, respectively. INTERPRETATION: In critically ill, term neonates, withholding parenteral nutrition for 1 week was clinically superior to standard care of initiating parenteral nutrition within 24 h for short-term outcomes. However, withholding parenteral nutrition for 1 week significantly increased the risk of developing hypoglycaemia, which necessitates long-term follow-up of these children before late parenteral nutrition can be confidently recommended for this vulnerable patient group. FUNDING: Flemish Agency for Innovation through Science and Technology, Methusalem-Programme Flemish Government, European Research Council, Fonds NutsOhra, Stichting Agis-Zorginnovatie, and the Sophia Research-Foundation. Options: A: Early PN significantly reduced in-hospital all-cause mortality and neonatal mortality. B: Late PN significantly reduced in-hospital all-cause mortality and neonatal mortality. C: There were no significant differences in in-hospital all-cause mortality and neonatal mortality between early and late PN. D: Early PN significantly increased in-hospital all-cause mortality and neonatal mortality.	B
4,622	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What were the main findings regarding the effectiveness of zinc supplementation in promoting growth and preventing infections in infants less than six months of age? Please answer this question based on the information provided below: Efficacy of combined iron and zinc supplementation on micronutrient status and growth in Vietnamese infants. OBJECTIVE: To evaluate the effect of combined iron-zinc supplementation on micronutrient status, growth and morbidity. DESIGN: Randomized, double-masked, placebo-controlled supplementation trial. SETTING: Rural district of Que Vo, in the Red River Delta in Vietnam. SUBJECTS: A total of 915 breast-fed infants aged 4-7 months were included and 784 completed the study. INTERVENTIONS: The Fe-group received daily and for a 6-month period 10 mg of iron, the Zn-group 10 mg zinc, the Fe-Zn group 10 mg iron+10 mg zinc and the placebo group a placebo. Hemoglobin (Hb), serum ferritin (SF) and zinc (SZn), and anthropometry were measured before and at the end of the intervention. Morbidity was recorded daily. RESULTS: Changes of Hb and SF were higher in both Fe and Fe+Zn groups (respectively 22.6 and 20.6 g/l for Hb; 36.0 and 24.8 microg/l for SF) compared to Zn and placebo groups (Hb: 6.4 and 9.8 g/l; SF: -18.2 and -16.9 microg/l, P<0.0001). SZn increased more in Zn group (10.3 micromol/l) than in Fe+Zn group (8.0 micromol/l, P=0.03) and more in these groups compared to Fe and placebo groups (1.6 and 1.2 micromol/l, P<0.0001). Weight gain was higher in the Zn group. No significant effects of supplementations on growth in length or morbidity. CONCLUSIONS: Combined iron-zinc supplementation had a positive effect on iron and zinc status in infants. However, the positive effect of zinc alone on SZn and weight would indicate a negative interaction of iron when added to zinc supplements. SPONSORSHIP: UNICEF New York. Zinc supplementation improved length growth only in anemic infants in a multi-country trial of iron and zinc supplementation in South-East Asia. Data from 4 randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam, the South-East Asian Multicountry Trial on Iron and Zinc supplementation in Infants (SEAMTIZI), were pooled to investigate the effects of iron and zinc supplementation infant growth. Infants (n = 2451) aged 4-6 mo old were supplemented with iron (10 mg/d) and/or zinc (10 mg/d) for 6 mo. Overall, neither iron nor zinc supplementation prevented the progressive growth faltering during infancy, which is common in many developing countries. However, infants who received zinc were less likely to be stunted at the end of the supplementation period (odds ratio 0.80; 95% CI 0.64-1.0). Boys had a 30% higher risk of being stunted at the end of the study than girls (P < 0.01). Baseline factors modified the effect of supplementation, with infants anemic at baseline (hemoglobin < 105 g/L) benefiting from zinc supplementation, with an estimated increase in height-for-age Z-score (HAZ) score of 0.17 (P < 0.01), but with no effect of zinc supplementation on growth in infants not anemic at baseline. Iron supplementation negatively affected linear growth in infants with a birth weight of >3500 g (estimated effect size, -0. 14 HAZ score; P < 0.01), but with no significant effect in infants with a lower birth weight. This study shows that blanket supplementation of infants with iron or zinc will not be beneficial to all recipients and may have adverse effects in some. Hence, interventions such as iron and zinc supplementation for infants should be restricted to subgroups in which there is a clear benefit and baseline factors should be considered and characterized before implementing new policies. Effects of iron and zinc supplementation in Indonesian infants on micronutrient status and growth. In this study the effects of supplementation of iron and zinc, alone or combined, on iron status, zinc status and growth in Indonesian infants is investigated. Micronutrient deficiencies are prevalent in infants in developing countries, and deficiencies often coexist; thus, combined supplementation is an attractive strategy. However, little is known about interactions between micronutrients. In a randomized, double-blind, placebo-controlled supplementation trial, 478 infants, 4 mo of age, were supplemented for 6 mo with iron (10 mg/d), zinc (10 mg/d), iron + zinc (10 mg of each/d) or placebo. Anthropometry was assessed monthly, and micronutrient status was assessed at the end of supplementation. Supplementation significantly reduced the prevalence of anemia, iron deficiency anemia and zinc deficiency. Iron supplementation did not negatively affect plasma zinc concentrations, and zinc supplementation did not increase the prevalence of anemia or iron deficiency anemia. However, iron supplementation combined with zinc was less effective than iron supplementation alone in reducing the prevalence of anemia (20% vs. 38% reduction) and in increasing hemoglobin and plasma ferritin concentrations. There were no differences among the groups in growth. The growth of all groups was insufficient to maintain the same Z-scores for height for age and weight for height. There is a high prevalence of deficiencies of iron and zinc in these infants, which can be overcome safely and effectively by supplementation of iron and zinc combined. However, overcoming these deficiencies is not sufficient to improve growth performance in these infants. Zinc supplementation improved length growth only in anemic infants in a multi-country trial of iron and zinc supplementation in South-East Asia. Data from 4 randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam, the South-East Asian Multicountry Trial on Iron and Zinc supplementation in Infants (SEAMTIZI), were pooled to investigate the effects of iron and zinc supplementation infant growth. Infants (n = 2451) aged 4-6 mo old were supplemented with iron (10 mg/d) and/or zinc (10 mg/d) for 6 mo. Overall, neither iron nor zinc supplementation prevented the progressive growth faltering during infancy, which is common in many developing countries. However, infants who received zinc were less likely to be stunted at the end of the supplementation period (odds ratio 0.80; 95% CI 0.64-1.0). Boys had a 30% higher risk of being stunted at the end of the study than girls (P < 0.01). Baseline factors modified the effect of supplementation, with infants anemic at baseline (hemoglobin < 105 g/L) benefiting from zinc supplementation, with an estimated increase in height-for-age Z-score (HAZ) score of 0.17 (P < 0.01), but with no effect of zinc supplementation on growth in infants not anemic at baseline. Iron supplementation negatively affected linear growth in infants with a birth weight of >3500 g (estimated effect size, -0. 14 HAZ score; P < 0.01), but with no significant effect in infants with a lower birth weight. This study shows that blanket supplementation of infants with iron or zinc will not be beneficial to all recipients and may have adverse effects in some. Hence, interventions such as iron and zinc supplementation for infants should be restricted to subgroups in which there is a clear benefit and baseline factors should be considered and characterized before implementing new policies. Zinc-iron, but not zinc-alone supplementation, increased linear growth of stunted infants with low haemoglobin. Zinc supplementation has been shown to benefit linear growth. However the effect may depend on whether zinc is the most limiting nutrient. This study aims to investigate the effect of supplementation with zinc-given alone or with iron and vitamin-A in improving infantsf micronutrient status and linear growth. The study was a double-blind-community-intervention study involving 800 infants aged 3-6 months in rural East Lombok, West Nusa Tenggara. Syrup consisting of zinc-alone, Zn (10 mg/d), zinc+iron, Zn+Fe (10 mg/d of each), zinc+iron+vitamin-A, Zn+Fe+vit.A (10 mg/d of each zinc and iron plus 1,000 IU vitamin-A), or placebo were given daily for six months. Outcomes measured were length, weight, and micronutrient status (haemoglobin, se-rum zinc, ferritin and retinol). Zn+Fe and Zn+Fe+vit.A supplementations benefit zinc and iron status of the sub-jects, while Zn-alone supplementation disadvantaged haemoglobin and iron status. The highest increment in vi-tamin A and haemoglobin status was shown in Zn+Fe+vit.A group. An effect on linear growth was observed among initially-stunted subjects in Zn+Fe and Zn+Fe+vit.A groups who grew 1.1-1.5 cm longer than placebo. On the other hand, in the Zn-alone group, mean height-for-age Z-score decreased to a greater extent than placebo. The between-group difference in HAZ among initially-stunted subjects was significant after four months sup-plementation. While the difference was not significant in follow-up after 6 months, the pattern remained the same where means height-for-age Z-score in Zn+Fe+vit.A and Zn+Fe groups were higher than placebo and Zn-alone groups. Given the low haemoglobin/iron status of the subjects, zinc supplementation would have positive effect on growth if the low haemoglobin/iron status is also addressed and corrected. Zinc supplementation does not affect growth, morbidity, or motor development of US term breastfed infants at 4-10 mo of age. BACKGROUND: It has been documented that growth patterns differ between breastfed and formula-fed infants. Some investigators have suggested that these differences may be related to differences in zinc nutriture. OBJECTIVE: The objective of this study was to examine the effect of zinc supplementation on growth, morbidity, and motor development in healthy, term, breastfed infants. DESIGN: We conducted a randomized double-blind intervention comparing zinc supplementation (5 mg/d as zinc sulfate) with placebo in breastfed infants aged 4-10 mo. Growth and indexes of body composition and gross motor development were measured monthly from 3 to 10 mo. Morbidity data were collected weekly. RESULTS: Eighty-five infants were enrolled, and 70 completed the study. The baseline characteristics, attained weight or length at 10 mo, growth velocity, gross motor development, and morbidity did not differ significantly between groups, even after control for potentially confounding variables. CONCLUSIONS: The dietary zinc intake of these breastfed infants appeared to be adequate, given that zinc supplementation did not affect growth, development, or risk of infection (although sample size for detection of differences in development or infection was limited). Previously described differences in growth between breastfed and formula-fed infants in such populations do not appear to be due to differences in zinc nutriture. Effectiveness of zinc supplementation to full term normal infants: a community based double blind, randomized, controlled, clinical trial. UNLABELLED: The study was aimed to test whether zinc supplementation, if initiated early, can prevent stunting and promote optimum body composition in full term infants. For this, full term pregnant women from low income urban community were enrolled and were followed-up for 24 months postpartum. Body mass index (BMI) was calculated from maternal weight and height that were collected one month after delivery. Infants' weight, and length, head, chest and mid upper arm circumferences and skin fold thicknesses at triceps, biceps and subscapular area were collected at baseline (before randomization) and once in three months up till 24 months. Three hundred and twenty four infants were randomized and allocated to zinc (163) or placebo (161) groups respectively. Supplementation of zinc was initiated from 4 months of age and continued till children attained 18 months. The control (placebo) group of children received riboflavin 0.5 mg/day, whereas the intervention (zinc) group received 5 mg zinc plus riboflavin 0.5 mg/day. When infants were 18 months old, dietary intakes (in 78 children) were calculated by 24 hour diet recall method and hemoglobin, zinc, copper and vitamin A were quantified in blood samples collected from 70 children. The results showed prevalence of undernutrition (body mass index <18.5) in 37% of the mothers. Mean±SD calorie consumption and zinc intakes from diets in infants were 590±282.8 Kcal/day and 0.97±0.608 mg/day respectively. Multiple linear regression models demonstrated maternal weight as a strong predictor of infants' weight and length at 18 months of age. As expected, diarrhea duration impacted infants' linear growth and weight gain adversely. Zinc supplementation for a mean period of 190 days, starting from 4 months up to 18 months of age, in full term normal infants, consuming an average energy of 590 Kcal/day, had significant effect on the skin fold thicknesses, but not on their linear growth. TRIAL REGISTRATION: Clinical Trail Registration India (CTRI) CTRI/2012/08/002884. Effect of zinc supplementation on mortality in children aged 1-48 months: a community-based randomised placebo-controlled trial. BACKGROUND: Studies from Asia have suggested that zinc supplementation can reduce morbidity and mortality in children, but evidence from malarious populations in Africa has been inconsistent. Our aim was to assess the effects of zinc supplementation on overall mortality in children in Pemba, Zanzibar. METHODS: We enrolled 42,546 children aged 1-36 months, contributing a total of 56,507 child-years in a randomised, double-blind, placebo-controlled trial in Pemba, Zanzibar. Randomisation was by household. 21 274 children received daily supplementation with zinc 10 mg (5 mg in children younger than 12 months) for mean 484.7 days (SD 306.6). 21,272 received placebo. The primary endpoint was overall mortality, and analysis was by intention to treat. This study is registered as an International Standard Randomised Clinical Trial, number ISRCTN59549825. FINDINGS: Overall, there was a non-significant 7% (95% CI -6% to 19%; p=0.29) reduction in the relative risk of all-cause mortality associated with zinc supplementation. INTERPRETATION: We believe that a meta-analysis of all studies of mortality and morbidity, will help to make evidence-based recommendations for the role of zinc supplementation in public health policy to improve mortality, morbidity, growth, and development in young children. Inconsistent effects of iron-folic acid and/or zinc supplementation on the cognitive development of infants. Despite concerns over the neurocognitive effects of micronutrient deficiencies in infancy, few studies have examined the effects of micronutrient supplementation on specific cognitive indicators. This study investigated, in 2002, the effects of iron-folic acid and/or zinc supplementation on the results of Fagan Test of Infant Intelligence (FTII) and the A-not-B Task of executive functioning among 367 Nepali infants living in Sarlahi district. Infants were enrolled in a cluster-randomized, placebo-controlled clinical trial of daily supplementation with 5 mg of zinc, 6.25 mg of iron with 25 microg of folic acid, or zinc-iron-folic acid, or placebo. These were tested on both the tasks using five indicators of information processing: preference for novelty (FTII), fixation duration (FTII), accelerated performance (> or = 85% correct; A-not-B), deteriorated performance (< 75% correct and > 1 error on repeat-following-correct trails; A-not-B), and the A-not-B error (A-not-B). At 39 and 52 weeks, 247 and 333 infants respectively attempted the cognitive tests; 213 made an attempt to solve both the tests. The likelihood of females completing the A-not-B Task was lower compared to males when cluster randomization was controlled [odds ratio = 0.67; 95% confidence interval 0.46-0.97; p < 0.05]. All of the five cognitive outcomes were modelled in linear and logistic regression. The results were not consistent across either the testing sessions or the information-processing indicators. Neither the combined nor the individual micronutrient supplements improved the performance on the FTII or the A-not-B Task (p > 0.05). These findings suggest that broader interventions (both in terms of scope and duration) are needed for infants who face many biological and social stressors. The role of zinc and iron-folic acid supplementation on early child temperament and eating behaviors in rural Nepal: a randomized controlled trial. UNLABELLED: Child eating behaviors play an important role in nutrient intake, ultimately affecting child growth and later outcomes in adulthood. The study assessed the effects of iron-folic acid and zinc supplementation on child temperament and child eating behaviors in rural Nepal. Children (N = 569) aged 4-17 months in Sarlahi district, southern Nepal were randomized to receive daily supplements of placebo, iron-folic acid, zinc, or zinc plus iron-folic acid and followed for approximately 1 year. At baseline and four follow-up visits mothers completed questionnaires including information on demographic characteristics and child temperament and eating behaviors. The main effects of zinc and iron-folic acid supplementation on temperament and eating behaviors were assessed through crude and adjusted differences in mean cumulative score changes between visits 1 and 5. The adjusted rate-of-change for these outcomes was modeled using generalized estimating equations. Mean changes in temperament scores and in eating behavior scores between visits 1 and 5 were not significant in either the zinc or non-zinc group. Children in the iron-folic acid group increased temperament scores by 0.37 points over 5 visits (95% CI 0.02, 0.7), which was not significant after adjustment. Neither the adjusted rate-of-change in temperament scores between zinc and non-zinc (β = -0.03, 95% CI -0.3, 0.2) or iron-folic acid and non-iron-folic acid (β = 0.08, 95% CI -0.2, 0.3) were significantly different. Adjusted rate of change analysis showed no significant difference between zinc and non-zinc (β = -0.14, 95% CI -0.3, 0.04) or between iron and non-iron eating behavior scores (β = -0.11, 95% CI -0.3, 0.1). Only among children with iron-deficiency anemia at baseline was there a significant decrease in eating behavior score, indicating better eating behaviors, when supplemented with zinc (β = -0.3, 95% CI -0.6, -0.01), Ultimately, this effect of zinc on eating behaviors was the only effect we observed after approximately one year of micronutrient supplementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00109551. Effect of daily zinc supplementation on child mortality in southern Nepal: a community-based, cluster randomised, placebo-controlled trial. BACKGROUND: Zinc supplementation can reduce subsequent morbidity in children recovering from diarrhoea and respiratory illness in developing countries. However, whether routine supplementation would decrease morbidity and mortality in populations with zinc deficiency is unclear. We assessed the effect of daily zinc supplementation on children in southern Nepal. METHODS: We did a community-based, cluster-randomised, double-masked, placebo-controlled, 2x2 factorial trial in children aged 1-35 months. Treatment groups were placebo, iron and folic acid, zinc, and iron and folic acid with zinc, with daily doses of 12.5 mg iron, 50 microg folic acid, and 10 mg zinc. Study staff gave children tablets on 2 days each week and left tablets with caregivers for other days. All children received vitamin A supplementation twice per year. Results of the iron arm of the trial have been reported previously. Between October, 2001, and January, 2006, 41,276 children were enrolled into the placebo (n=20,308) or zinc (n=20,968) groups and were followed-up for 60,636.3 person-years. The primary outcome was child mortality, and analyses were by intention to treat. Daily reports of signs and symptoms of common morbidities in stratified random subsamples of children were assessed every week for 12 months. This study is registered at ClinicalTrials.gov, number NCT00109551. FINDINGS: 2505 children refused to continue the trial and 3219 children were lost to follow-up. There was no significant difference in mortality between the zinc and placebo groups (316 vs 333 deaths; hazard ratio 0.92, 95% CI 0.75-1.12). Zinc had no effect on mortality in children younger than 12 months (181 vs 168 deaths; 1.04, 0.83-1.31); mortality was lower, but not statistically significantly so, in older children receiving zinc (135 vs 165; 0.80, 0.60-1.06). The frequency and duration of diarrhoea, persistent diarrhoea, dysentery, and acute lower respiratory infections did not differ between the groups. INTERPRETATION: Total mortality of children receiving zinc supplementation was not significantly different from that of children receiving placebo. Further data are needed from other populations with endemic zinc deficiency to confirm the potential age-specific effects reported in this study. Effect of routine prophylactic supplementation with iron and folic acid on preschool child mortality in southern Nepal: community-based, cluster-randomised, placebo-controlled trial. INTRODUCTION: Iron deficiency is widespread in the developing world and is especially common in young children who live on the Indian subcontinent. Supplementation with iron and folic acid alleviates severe anaemia and enhances neurodevelopment in deficient populations, but little is known about the risks of mortality and morbidity associated with supplementation. METHODS: We did a community-based, cluster-randomised, double-masked, placebo-controlled, 2x2 factorial trial in children aged 1-36 months and residing in southern Nepal. We randomly assigned children daily oral supplementation to age 36 months with: iron (12.5 mg) and folic acid (50 microg; n=8337), zinc alone (10 mg), iron, folic acid, and zinc (n=9230), or placebo (n=8683); children aged 1-11 months received half the dose. Our primary outcome measure was all-cause mortality, and our secondary outcome measures included cause-specific mortality and incidence and severity of diarrhoea, dysentery, and acute respiratory illness. Analyses were by intention to treat. This study is registered at , number NCT00109551. FINDINGS: The iron and folic acid-containing groups of the study were stopped early in November, 2003, on the recommendation of the data and safety monitoring board; mortality in these groups did not differ from placebo and there was low power to detect positive or negative effects by the time enrollment was completed. We continued to enroll children to the placebo and zinc alone groups. 25,490 children participated and analyses are based on 29,097.3 person-years of follow-up. There was no difference in mortality between the groups who took iron and folic acid without or with zinc when compared with placebo (HR 1.03, 95% CI 0.78-1.37, and 1.00, 0.74-1.34, respectively). There were no significant differences in the attack rates for diarrhoea, dysentery, or respiratory infections between groups, although all the relative risks except one indicated modest, non-significant protective effects. INTERPRETATION: Daily supplementation of young children in southern Nepal with iron and folic acid with or without zinc has no effect on their risk of death, but might protect against diarrhoea, dysentery, and acute respiratory illness. Zinc supplementation improved length growth only in anemic infants in a multi-country trial of iron and zinc supplementation in South-East Asia. Data from 4 randomized, placebo-controlled, double-blind trials in Indonesia, Thailand, and Vietnam, the South-East Asian Multicountry Trial on Iron and Zinc supplementation in Infants (SEAMTIZI), were pooled to investigate the effects of iron and zinc supplementation infant growth. Infants (n = 2451) aged 4-6 mo old were supplemented with iron (10 mg/d) and/or zinc (10 mg/d) for 6 mo. Overall, neither iron nor zinc supplementation prevented the progressive growth faltering during infancy, which is common in many developing countries. However, infants who received zinc were less likely to be stunted at the end of the supplementation period (odds ratio 0.80; 95% CI 0.64-1.0). Boys had a 30% higher risk of being stunted at the end of the study than girls (P < 0.01). Baseline factors modified the effect of supplementation, with infants anemic at baseline (hemoglobin < 105 g/L) benefiting from zinc supplementation, with an estimated increase in height-for-age Z-score (HAZ) score of 0.17 (P < 0.01), but with no effect of zinc supplementation on growth in infants not anemic at baseline. Iron supplementation negatively affected linear growth in infants with a birth weight of >3500 g (estimated effect size, -0. 14 HAZ score; P < 0.01), but with no significant effect in infants with a lower birth weight. This study shows that blanket supplementation of infants with iron or zinc will not be beneficial to all recipients and may have adverse effects in some. Hence, interventions such as iron and zinc supplementation for infants should be restricted to subgroups in which there is a clear benefit and baseline factors should be considered and characterized before implementing new policies. Long-term effects of iron and zinc supplementation during infancy on cognitive function at 9 y of age in northeast Thai children: a follow-up study. BACKGROUND: Iron and zinc are important micronutrients for child growth and development. One would expect that iron and zinc supplementation in infancy would affect long-term cognitive development and school achievement, but this has not been evaluated. OBJECTIVE: We investigated the effect of iron or zinc supplementation or both during infancy on cognitive performance 8 y later. DESIGN: A follow-up study was performed in 560 children aged 9 y or 92% of those who had participated in a randomized controlled trial involving 4 groups who received daily iron, zinc, iron plus zinc, or a placebo at 4-6 mo of age for 6 mo. Cognitive performance was assessed by using the Wechsler Intelligence Scale for Children-Third Edition (Thai version), the Raven's Colored Progressive Matrices (CPM), and school performance tests. General linear mixed models were used to assess long-term effects. RESULTS: No significant differences in any of the outcomes at 9 y of age were observed at follow-up between the 4 groups. Mean intelligence quotients ranged across groups from 92.9 to 93.7 for full scale, 93.9-95.4 for verbal, and 93.1-94.0 for performance. The Raven's CPM score ranged from 21.4 to 22.4. CONCLUSION: Supplementation with iron or zinc or both during infancy does not lead to long-term cognitive improvement in 9-y-old children. This trial was registered at clinicaltrials.gov as NCT00824304. Iron and zinc supplementation improved iron and zinc status, but not physical growth, of apparently healthy, breast-fed infants in rural communities of northeast Thailand. Iron deficiency is prevalent in children and infants worldwide. Zinc deficiency may be prevalent, but data are lacking. Both iron and zinc deficiency negatively affect growth and psychomotor development. Combined iron and zinc supplementation might be beneficial, but the potential interactions need to be verified. In a randomized, placebo-controlled trial using 2 x 2 factorial design, 609 Thai infants aged 4-6 mo were supplemented daily with 10 mg of iron and/or 10 mg of zinc for 6 mo to investigate effects and interactions on micronutrient status and growth. Iron supplementation alone increased hemoglobin and ferritin concentrations more than iron and zinc combined. Anemia prevalence was significantly lower in infants receiving only iron than in infants receiving iron and zinc combined. Baseline iron deficiency was very low, and iron deficiency anemia was almost nil. After supplementation, prevalence of iron deficiency and iron deficiency anemia were significantly higher in infants receiving placebo and zinc than in those receiving iron or iron and zinc. Serum zinc was higher in infants receiving zinc (16.7 +/- 5.2 micromol/L), iron and zinc (12.1 +/- 3.8 micromol/L) or iron alone (11.5 +/- 2.5 micromol/L) than in the placebo group (9.8 +/- 1.9 micromol/L). Iron and zinc interacted to affect iron and zinc status, but not hemoglobin. Iron supplementation had a small but significant effect on ponderal growth, whereas zinc supplementation did not. To conclude, in Thai infants, iron supplementation improved hemoglobin, iron status, and ponderal growth, whereas zinc supplementation improved zinc status. Overall, for infants, combined iron and zinc supplementation is preferable to iron or zinc supplementation alone. Options: A: Zinc supplementation significantly improved weight-for-age and weight-for-length Z-scores after six months of intervention, but had no effect on mortality or incidence of diarrhoea and respiratory infections. B: Zinc supplementation had no significant impact on growth outcomes, but significantly reduced the incidence of diarrhoea and respiratory infections. C: Zinc supplementation significantly improved growth outcomes and reduced both mortality and the incidence of infections in infants. D: Zinc supplementation had no significant impact on growth outcomes, mortality, or incidence of infections.	A
4,623	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What were the findings regarding the impact of agricultural education interventions aimed at reducing aflatoxin exposure on infant weight-for-age z-scores (WAZ) in low- and middle-income countries? Please answer this question based on the information provided below: Post-harvest practices for aflatoxin control: Evidence from Kenya. We assess the impact of a package of post-harvest technologies on aflatoxin contamination of maize through a randomized trial in rural Kenya. Some elements of this package (training and provision of plastic sheets for sun-drying) were provided free of charge to all participants in treatment villages and were widely adopted. Others (a mobile drying service and hermetic storage bags) were provided free to a subset of randomly selected farmers in treatment villages while others had to pay. Overall, the intervention reduced aflatoxin contamination by over 50%. Most of this reduction appears to be due training and the use of drying sheets, the lowest-cost of all the technologies offered. Options: A: Agricultural education interventions had no significant impact on infant WAZ. B: Agricultural education interventions significantly decreased infant WAZ. C: Agricultural education interventions may improve infant WAZ. D: Agricultural education interventions significantly increased linear growth in infants.	C
4,624	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What were the findings regarding the treatment of distal deep vein thrombosis (DVT) with anticoagulation therapy using vitamin K antagonists (VKA) compared to no intervention or placebo? Please answer this question based on the information provided below: Optimal duration of treatment in surgical patients with calf venous thrombosis involving one or more veins. The aim of this study was to evaluate different durations of treatment in patients with calf venous thrombosis (CVT) involving 1 or more deep veins. The authors studied 2 groups of patients with postsurgical CVT diagnosed by echo-color Doppler. The first group consisted of 68 patients with CVT involving a single vein, and the second group consisted of 124 patients with CVT involving 2 or more veins. Immediately after diagnosis, all patients were treated with nadroparin calcium and sodium warfarin. Heparin treatment was withdrawn after 5-6 days of treatment, when the international normalized ratio (INR) was stabilized between 2 and 3. Each group was divided into 2 subgroups receiving anticoagulation treatment for 6 or 12 weeks, respectively. The endpoint was proximal extension of the thrombotic lesion, defined as the extension of the thrombus to the popliteal and/or femoral vein. In patients with single-vessel CVT there was no significant difference between the 2 subgroups, whereas in patients with CVT involving 2 or more vessels, a statistically significant difference was observed, the number of cases showing proximal extension of the thrombus being higher among patients treated for 6 weeks. Twelve weeks of anticoagulation treatment is better than 6 weeks only in patients with postsurgical CVT involving 2 or more veins. The anticoagulation of calf thrombosis (ACT) project: results from the randomized controlled external pilot trial. BACKGROUND: There is currently little evidence defining the clinical importance of detecting and treating isolated distal DVT (IDDVT). International guidelines vary regarding diagnostic and therapeutic advice. The potential benefits of anticoagulation are unquantified. We sought to evaluate the feasibility of a randomized controlled study within a modern framework and provide a primary outcome point estimate. METHODS: In this open-label, external pilot randomized controlled trial, consecutive, symptomatic, ambulatory patients with IDDVT were approached for inclusion. Participants were allocated to receive either therapeutic anticoagulation or conservative management. Patients underwent blinded color-duplex imaging at 7 and 21 days and follow-up at 3 months. Principal feasibility outcomes included recruitment rate and attrition. The principal clinical outcome was a composite including proximal propagation, pulmonary embolism, death attributable to VTE disease, or major bleeding. Analysis was by intention to treat. RESULTS: In total, 93 patients with IDDVT were screened, and 70 of those eligible (88.6%) were recruited. All patients but one were followed-up by direct contact after 90 days. Allocation crossover occurred in 15 patients (21.4%). The principal clinical outcome occurred in four of 35 of those conservatively treated (11.4%) and zero of 35 in the anticoagulated group (absolute risk reduction, 11.4%; 95% CI, -1.5 to 26.7, P = .11, number needed to treat of nine). There were no major bleeding episodes. CONCLUSIONS: We have established the feasibility of definitive study regarding the value of therapeutic anticoagulation in IDDVT and provide an approximate point estimate for serious complications with a contemporary conservative strategy. TRIAL REGISTRY: Current Controlled Trials; No.: ISRCTN75175695; URL: www.controlled-trials.com. The Anticoagulation of Calf Thrombosis (ACT) project: study protocol for a randomized controlled trial. BACKGROUND: Half of all lower limb deep vein thrombi (DVT) in symptomatic ambulatory patients are located in the distal (calf) veins. While proximal disease warrants therapeutic anticoagulation to reduce the associated risks, distal DVT often goes untreated. However, a proportion of untreated distal disease will undoubtedly propagate or embolize. Concern also exists that untreated disease could lead to long-term post thrombotic changes. Currently, it is not possible to predict which distal thrombi will develop such complications. Whether these potential risks outweigh those associated with unrestricted anticoagulation remains unclear. The Anticoagulation of Calf Thrombosis (ACT) trial aims to compare therapeutic anticoagulation against conservative management for patients with acute symptomatic distal deep vein thrombosis. METHODS: ACT is a pragmatic, open-label, randomized controlled trial. Adult patients diagnosed with acute distal DVT will be allocated to either therapeutic anticoagulation or conservative management. All patients will undergo 3 months of clinical and assessor blinded sonographic follow-up, followed by 2-year final review. The project will commence initially as an external pilot study, recruiting over a 16-month period at a single center to assess feasibility measures and clinical event rates. Primary outcome measures will assess feasibility endpoints. Secondary clinical outcomes will be collected to gather accurate data for the design of a definitive clinical trial and will include: (1) a composite endpoint combining thrombus propagation to the popliteal vein or above, development of symptomatic pulmonary embolism or sudden death attributable to venous thromboembolic disease; (2) the incidence of major and minor bleeding episodes; (3) the incidence of post-thrombotic leg syndrome at 2 years using a validated screening tool; and (4) the incidence of venous thromboembolism (VTE) recurrence at 2 years. DISCUSSION: The ACT trial will explore the feasibility of comparing therapeutic anticoagulation to conservative management in acute distal DVT, within a modern cohort. We also aim to provide contemporary data on clot propagation, bleeding rates and long-term outcomes within both groups. These results will inform the conduct of a definitive study if feasibility is established. Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis. The need for oral anticoagulation in patients with calf-vein thrombosis was examined in a randomised study of 51 patients, of whom 23 received warfarin for 3 months and 28 did not. Both groups received an initial course of heparin and all wore compression stockings. Progress was monitored by the use of serial isotope tests and physical examination. Phlebography was repeated if recurrence was suspected. During the first 3 months, 8 patients in the non-warfarin group (29%) had recurrences compared with none in the warfarin group (p less than 0.01). 5 patients had recurrence with proximal extension and 1 patient had a pulmonary embolus. After 1 year, 22 out of 23 patients in the warfarin group had not had a recurrence, compared with 19 out of 28 (p less than 0.02). The findings indicate that oral anticoagulants should be given to all patients with thrombi that produce symptoms. Treatment for 3 months seems to be sufficient. Anticoagulant therapy in deep venous thrombosis. A randomized controlled study. Ninety patients with venographically proven deep venous thrombosis(DVT) but without clinical signs of pulmonary embolism(PE) were randomized into two different treatment regimens to compare the safety and efficacy of continuous intravenous heparin and oral anticoagulant(AC) treatment versus non-AC treatment. All patients in the two treatment groups were actively mobilized from the day of admission and wore graduated compressing stockings. In the non-AC-group the patients were treated with phenylbutazone for ten days. Treatment with heparin was maintained for 6 days and oral AC treatment was given from the third day and continued for 3 months. Venography was repeated after 30 days. A perfusion-ventilation lung scan was performed on day 1-2, 10 and 60. In fifty-nine patients a revenography was performed, twenty nine in the AC-group and thirty in the non-AC group. For distal veins regression was found in nine and eight respectively (4.4% in favour of AC, 95% confidence limit 27.5% to -18.7%) and in proximal veins regression was found in five and eight, respectively (10.9% in favour of AC, 95% confidence limit 32.0% to -10.1%). No difference in lung scans was found after 10 days (0.8% in favour of AC, 95% confidence limit 21.5% to -19.9%) or after 60 days (3.3% in favour of non-AC treatment, 95% confidence limit 21.8% to -28.5%). In the AC group the incidence of bleeding complications was 8.3%. No side-effects of phenylbutazone was found. The present controlled clinical study demonstrated no effect of AC-treatment on DVT progression in actively mobilized patients wearing graduated compressing stockings when compared to a non-AC treated group receiving analgetic therapy with phenylbutazone. However, the patient population of the study is relatively small with wide confidence intervals for differences between groups. Before more general recommendations can be made, a large scale placebo-controlled study is needed to evaluate the possible effect of AC-treatment in DVT patients, who can be mobilized from the first day. Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. BACKGROUND: The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism remains controversial. METHODS AND RESULTS: We performed an open-label, randomized trial comparing a short oral anticoagulant course (3 months for proximal deep vein thrombosis [P-DVT] and/or pulmonary embolism [PE]; 6 weeks for isolated calf DVT [C-DVT]) with a long course of therapy (6 months for P-DVT/PE; 12 weeks for C-DVT). The outcome events were recurrences and major, minor, or fatal bleeding complications. A total of 736 patients were enrolled. There were 23 recurrences of venous thromboembolism in the short treatment group (6.4%) and 26 in the long treatment group (7.4%); the 2 treatment regimens had an equivalent effect. For the hemorrhage end point, the difference between the short and the long treatment groups was not significant: 15.5% versus 18.4% for all events (P=0.302), 1.7% versus 2.8% (P=0.291) for major events, and 13.9% versus 15.3% for minor bleeding. Subgroup analysis demonstrated that the rate of recurrence was lower for C-DVT than for P-DVT or PE. CONCLUSIONS: After isolated C-DVT, 6 weeks of oral anticoagulation is sufficient. For P-DVT or PE, we demonstrated an equivalence between 3 and 6 months of anticoagulant therapy. For patients with temporary risk factors who have a low risk of recurrence, 3 months of treatment seems to be sufficient. For patients with idiopathic venous thromboembolism or permanent risk factors who have a high risk of recurrence, other trials are necessary to assess prolonged therapy beyond 6 months. Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial. BACKGROUND: The efficacy and safety of anticoagulant treatment is not established for patients with acute symptomatic deep vein thrombosis (DVT) of the calf. We aimed to assess whether therapeutic anticoagulation is superior to placebo in patients with symptomatic calf DVT. METHODS: In this randomised, double-blind, placebo-controlled trial, we enrolled low-risk outpatients (without active cancer or previous venous thromboembolic disease) with a first acute symptomatic DVT in the calf from 23 university medical centres or community medical clinics in Canada, France, and Switzerland. We randomly assigned (1:1) patients to receive either the low-molecular-weight heparin nadroparin (171 UI/kg, subcutaneously, once a day) or placebo (saline 0·9%, subcutaneously, once a day) for 6 weeks (42 days). Central randomisation was done using a computer-generated randomisation list, stratified by study centre. Random allocation sequences of variable block size were centrally determined by an independent research clinical centre. Study staff, patients, and outcome assessors (central adjudication committee) were masked to group assignment. Numbered boxes of active drug or placebo were provided to pharmacies in identical packaging. All patients were prescribed compression stockings and followed up for 90 days. The primary efficacy outcome was a composite measure of extension of calf DVT to proximal veins, contralateral proximal DVT, and symptomatic pulmonary embolism at day 42 in the modified intention-to-treat population. The primary safety outcome was major or clinically relevant non-major bleeding at day 42. The trial was registered with ClinicalTrials.gov, number NCT00421538. FINDINGS: Between Feb 1, 2008, and Nov 30, 2014, we screened 746 patients, enrolling 259 patients (50% of the prespecified sample size), before the trial steering committee terminated the trial because of expiry of study drug and slow recruitment. The intention-to-treat analysis population comprised 122 patients in the nadroparin group and 130 in the placebo group. There was no significant difference between the groups in the composite primary outcome, which occurred in four patients (3%) in the nadroparin group and in seven (5%) in the placebo group (risk difference -2·1%, 95% CI -7·8 to 3·5; p=0·54). Bleeding occurred in five patients (4%) in the nadroparin group and no patients in the placebo group (risk difference 4·1, 95% CI 0·4 to 9·2; p=0·0255). In the nadroparin group one patient died from metastatic pancreatic cancer and one patient was diagnosed with heparin-induced thrombocytopenia type 2. INTERPRETATION: Nadroparin was not superior to placebo in reducing the risk of proximal extension or venous thromboembolic events in low-risk outpatients with symptomatic calf DVT, but did increase the risk of bleeding. Avoidance of systematic anticoagulation for calf DVT could have a substantial impact on individual patients and from a public health perspective. FUNDING: Swiss National Science Foundation, the Programme Hospitalier de Recherche Clinique in France, and the Canadian Institutes of Health Research. Effect of anticoagulant treatment on pain in distal deep vein thrombosis: an ancillary analysis from the cactus trial. Essentials Management of patients with calf deep vein thrombosis remains controversial. We conducted a post-hoc analysis of a placebo controlled LMWH randomized clinical trial. Pain was assessed using visual analogue scale at inclusion, one and six weeks. There was no difference in pain control between the two arms. SUMMARY: Background The optimal management of distal deep vein thrombosis (DVT) is highly debated. The only available placebo-controlled trial suggested the absence of clear benefit of anticoagulation. Many physicians feel that, beyond preventing thromboembolic complications, anticoagulation with low-molecular-weight heparin (LMWH) has the potential to improve pain control. Objectives To analyze whether LMWHs decrease pain in patients with distal deep vein thrombosis. Patients and methods Two-hundred and fifty-two patients included in a multicenter, placebo-controlled, randomized clinical trial of LMWH in patients with acute distal DVT and who were asked to rate their pain at inclusion and at each medical visit, using a visual analogue pain scale (VAS). Results One hundred and thirty patients were randomized in the therapeutic nadroparin arm and 122 patients were randomized in the placebo arm. Mean VAS values were 4.6 (standard deviation [SD] 2.5) at inclusion, 2.1 (SD 2.0) at 1 week and 0.4 (SD 1.2) at 6 weeks. We calculated the individual variation in VAS between inclusion and 1 week in patients in whom VAS was available at the two study time-points. There was no difference in the mean VAS reduction between patients treated with therapeutic nadroparin (n = 106) and with placebo (n = 109): -2.6 (SD 2.4) vs. -2.3 (SD 2.0) after 1 week and -4.4 (SD 2.8) vs. -4.0 (SD 2.4) after 6 weeks, respectively. The use of compression stockings was associated with a reduction in pain. Conclusion These data suggests that LMWH use does not improve pain control as compared with placebo in patients with acute distal DVT. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group. BACKGROUND: The optimal duration of oral anticoagulant therapy after a first episode of venous thromboembolism is still a matter of debate. METHODS: We performed a multicenter trial comparing six weeks of oral anticoagulant treatment with six months of such therapy in patients who had a first episode of venous thromboembolism. Anticoagulant therapy consisted of warfarin or dicumarol. Of the 902 patients enrolled, 5 were later excluded because they had congenital protein C deficiency; 443 were randomly assigned to receive six weeks of oral anticoagulant therapy with a targeted international normalized ratio (INR) of 2.0 to 2.85, and 454 were randomly assigned to receive six months of such therapy. The initial diagnoses were confirmed by means of venography in cases of deep-vein thromboses (n = 790) and with perfusion-ventilation scanning or angiography in cases of pulmonary embolism (n = 107); recurrences were confirmed in the same way. RESULTS: After two years of follow-up, there had been 123 recurrences of venous thromboembolism that met the diagnostic criteria, 80 in the six-week group (18.1 percent; 95 percent confidence interval, 14.5 to 21.6) and 43 in the six-month group (9.5 percent; 95 percent confidence interval, 6.8 to 12.2). The odds ratio for recurrence in the six-week group was 2.1 (95 percent confidence interval, 1.4 to 3.1). There was no difference in mortality or the rate of major hemorrhage between the six-week and six-month groups. CONCLUSIONS: Six months of prophylactic oral anticoagulation after a first episode of venous thromboembolism led to a lower recurrence rate than did treatment lasting for six weeks. The difference between the two groups occurred between 6 weeks and 6 months after the start of treatment, and the rates of recurrence remained nearly parallel for 1 1/2 years thereafter. Therapy of isolated calf muscle vein thrombosis: a randomized, controlled study. BACKGROUND: Treatment of isolated calf muscle vein thrombosis (ICMVT) is controversial. There are no data from prospective, controlled studies. Objective of this article was to compare the efficacy and safety of a short-term course of anticoagulation with compression therapy alone. METHODS: We prospectively randomized patients with symptomatic, sonographically proven ICMVT in the soleal and/or gastrocnemial muscle veins in two treatment arms. The first received low-molecular-weight heparin for 10 days at therapeutic dosage (nadroparin 180 anti-activated factor X units once daily) and compression therapy for three months, and the second received compression therapy alone. Primary efficacy endpoint of the study was sonographically proven progression of ICMVT into the deep veins and clinical pulmonary embolism (PE) as confirmed by objective testing. Secondary efficacy and primary safety endpoints were major bleeding, death not due to PE, and complete sonographically proven recanalization of the muscle vein. We assessed transient and permanent risk factors for venous thromboembolism. RESULTS: One-hundred seven patients were finally ruled eligible for evaluation: 89% outpatients, 11% hospitalized patients. In the heparin group (n=54) progression to deep vein thrombosis (DVT) occurred in two patients (3.7%), in the group compression therapy alone (n=53) progression to DVT occurred in two patients (n.s.). No clinical PE and no death occurred. Thrombus recanalization after 3 months was not statistically significant different between the two study groups. No major bleeding occurred. CONCLUSION: The data do not show superiority of a short-term regimen of low-molecular-weight heparin and compression therapy in comparison with compression therapy alone in patients with ICMVT in a rather low-risk population. Options: A: Anticoagulation therapy with VKA significantly reduced the risk of recurrent venous thromboembolism (VTE) with little or no difference in major bleeding events, but increased clinically relevant non-major bleeding. B: Anticoagulation therapy with VKA had no significant effect on the risk of recurrent VTE and increased the risk of major bleeding events. C: Anticoagulation therapy with VKA significantly increased the risk of recurrent VTE and had no effect on major bleeding events. D: Anticoagulation therapy with VKA had no significant effect on the risk of recurrent VTE and decreased the risk of clinically relevant non-major bleeding.	A
4,625	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the conclusion regarding the effectiveness and safety of omega-3 fatty acid supplementation for people with cystic fibrosis? Please answer this question based on the information provided below: The clinical benefits of long-term supplementation with omega-3 fatty acids in cystic fibrosis patients - A pilot study. Effectiveness of omega-3 supplementation in cystic fibrosis (CF) remains controversial. This study sought to evaluate clinical status, exercise tolerance, inflammatory parameters, and erythrocyte fatty acid profile after 1 year of oral omega-3 supplementation in CF patients. Fifteen ΔF508-homozygous patients undergoing chronic azithromycin were randomized to receive omega-3 fish oil supplementation at a dose of 60mg/Kg/day or placebo. In comparison with the previous year, in the supplemented group, the number of pulmonary exacerbations decreased at 12 months (1.7 vs. 3.0, p<0.01), as did the duration of antibiotic therapy (26.5 days vs. 60.0 days, p<0.025). Supplementation significantly increased the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as early as <3 months of administration, with concomitant decreases in arachidonic acid (AA) levels. This pilot study suggests that long-term omega-3 supplementation offers several clinical benefits as to the number of exacerbations and duration of antibiotic therapy in CF patients. Oral absorption of omega-3 fatty acids in patients with cystic fibrosis who have pancreatic insufficiency and in healthy control subjects. Dietary supplementation with fish oils high in the omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, may have an antiinflammatory effect. We determined whether patients with cystic fibrosis (CF) could incorporate omega-3 fatty acids into their plasma and cell membrane phospholipids without adverse effects. In this double-blind study, 12 patients with pancreatic insufficiency who have CF (mean age, 12.2 +/- 5.4 (SD) years) and 13 subjects without CF (mean age, 13.4 +/- 6.3 (SD) years) were randomly assigned to ingest 8 gm daily of either encapsulated fish oil (3.2 gm of eicosapentaenoic acid and 2.2 gm of docosahexaenoic acid daily) or olive oil ethyl esters for 6 weeks. Two of seven and two of five patients with CF who received fish and olive oils, respectively, and one of eight and none of five subjects without CF discontinued taking the capsules before 6 weeks because of eructation or diarrhea. Significant incorporation of omega-3 fatty acids into plasma and erythrocyte membrane phospholipids was observed in subjects with and those without CF randomly assigned to the fish oil treatment. For example, in subjects randomly assigned to receive fish oil, the eicosapentaenoic acid/arachidonic acid ratio in plasma increased 9.8-fold, from 0.04 +/- 0.02 (mean +/- SEM) to 0.39 +/- 0.11 (p = 0.02), in the patients with CF (n = 7) and 23.0-fold, from 0.04 +/- 0.01 to 0.92 +/- 0.17 (p = 0.001), in the subjects without CF (n = 8) who received fish oil (p = 0.02, patients with CF vs subjects without CF at 6 weeks). No clinically or statistically significant changes from baseline were observed in platelet aggregation or levels of vitamin E or A in subjects who received fish oil. Future studies are indicated to determine whether omega-3 fatty acid enrichment provides a clinically beneficial antiinflammatory effect in patients with CF. Oral absorption of omega-3 fatty acids in patients with cystic fibrosis who have pancreatic insufficiency and in healthy control subjects. Dietary supplementation with fish oils high in the omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, may have an antiinflammatory effect. We determined whether patients with cystic fibrosis (CF) could incorporate omega-3 fatty acids into their plasma and cell membrane phospholipids without adverse effects. In this double-blind study, 12 patients with pancreatic insufficiency who have CF (mean age, 12.2 +/- 5.4 (SD) years) and 13 subjects without CF (mean age, 13.4 +/- 6.3 (SD) years) were randomly assigned to ingest 8 gm daily of either encapsulated fish oil (3.2 gm of eicosapentaenoic acid and 2.2 gm of docosahexaenoic acid daily) or olive oil ethyl esters for 6 weeks. Two of seven and two of five patients with CF who received fish and olive oils, respectively, and one of eight and none of five subjects without CF discontinued taking the capsules before 6 weeks because of eructation or diarrhea. Significant incorporation of omega-3 fatty acids into plasma and erythrocyte membrane phospholipids was observed in subjects with and those without CF randomly assigned to the fish oil treatment. For example, in subjects randomly assigned to receive fish oil, the eicosapentaenoic acid/arachidonic acid ratio in plasma increased 9.8-fold, from 0.04 +/- 0.02 (mean +/- SEM) to 0.39 +/- 0.11 (p = 0.02), in the patients with CF (n = 7) and 23.0-fold, from 0.04 +/- 0.01 to 0.92 +/- 0.17 (p = 0.001), in the subjects without CF (n = 8) who received fish oil (p = 0.02, patients with CF vs subjects without CF at 6 weeks). No clinically or statistically significant changes from baseline were observed in platelet aggregation or levels of vitamin E or A in subjects who received fish oil. Future studies are indicated to determine whether omega-3 fatty acid enrichment provides a clinically beneficial antiinflammatory effect in patients with CF. Supplementation with fatty acids influences the airway nitric oxide and inflammatory markers in patients with cystic fibrosis. OBJECTIVES: To obtain a balance in the fatty acid (FA) metabolism is important for the inflammatory response and of special importance in cystic fibrosis (CF), which is characterized by impaired FA metabolism, chronic inflammation, and infection in the airways. Nitric oxide (NO) has antimicrobial properties and low nasal (nNO) and exhaled NO (FENO), commonly reported in CF that may affect bacterial status. The present study investigates the effect of different FA blends on nNO and FENO and immunological markers in patients with CF. PATIENTS AND METHODS: Forty-three patients with CF and "severe" mutations were consecutively enrolled in a randomized double-blind placebo-controlled study with 3 FA blends containing mainly n-3 or n-6 FA or saturated FA acting as placebo. FENO, nNO, serum phospholipid concentrations of FA, and biomarkers of inflammation were measured before and after 3 months of supplementation. RESULTS: Thirty-five patients in clinically stable condition completed the study. The serum phospholipid FA pattern changed significantly in all 3 groups. An increase of the n-6 FA, arachidonic acid, was associated with a decrease of FENO and nNO. The inflammatory biomarkers, erythrocyte sedimentation rate, and interleukin-8 decreased after supplementation with n-3 FA and erythrocyte sedimentation rate increased after supplementation with n-6 FA. CONCLUSIONS: This small pilot study indicated that the composition of dietary n-3 and n-6 FA influenced the inflammatory markers in CF. FENO and nNO were influenced by changes in the arachidonic acid concentration, supporting previous studies suggesting that both the lipid abnormality and the colonization with Pseudomonas influenced NO in the airways. Eicosapentaenoic acid in cystic fibrosis: evidence of a pathogenetic role for leukotriene B4. Much of the lung damage that limits the life of young adults with cystic fibrosis is due to proteases and oxygen metabolites generated by neutrophils, which are recruited into the airway by the interaction between Pseudomonas aeruginosa and pulmonary macrophages. Leukotriene B4 (LTB4) has been proposed as a local mediator of this process; its production is susceptible to specific modulation with dietary eicosapentaenoic acid (EPA). We carried out a placebo-controlled trial of EPA (2.7 g daily for 6 weeks) to assess its effects on markers of clinical state, peripheral neutrophil function, and lung inflammation in sixteen patients with cystic fibrosis colonised with P aeruginosa. EPA was well tolerated and resulted in a significant reduction in sputum volume (median change with EPA -10 mL/day, placebo 0; p = 0.015), and improvements in Schwachman score (EPA 5%, placebo 0; p = 0.034), forced expiratory volume in 1 s (EPA 0.25 L, placebo -0.1 L; p = 0.006), and vital capacity (EPA 0.6 L, placebo 0; p = 0.011). Relative chemotaxis of circulating neutrophils to LTB4 increased from a subnormal baseline of 4 (median; range 0-10) microns/30 min before treatment, to a near normal value of 11 (5-18) microns/30 min after EPA. Relative chemotaxis to LTB4 of patients taking placebo did not change: the difference in response was highly significant (p = 0.001). Specific reduction of neutrophil chemotaxis to LTB4 is a sensitive assay of chronic in-vivo exposure to LTB4. Our results suggest that LTB4 has a pathogenetic role in the lung damage of cystic fibrosis. Longer-term clinical trials of EPA are warranted in a larger number of cystic fibrosis patients. Biological effects of a dietary omega-3 polyunsaturated fatty acids supplementation in cystic fibrosis patients: a randomized, crossover placebo-controlled trial. BACKGROUND AND AIMS: Various anti-inflammatory therapies, including dietary omega-3 polyunsaturated fatty acids (PUFA) supplementation, have been investigated in cystic fibrosis (CF) patients. To further explore this nutritional approach, biological effects of an omega-3 PUFA oral liquid supplementation were measured in 17 CF patients in a double-blind, randomized, crossover without a washout period and placebo-controlled study. METHODS: CF patients (age: 18+/-9 year; weight: 43+/-13 kg) received a liquid dietary supplementation either enriched or not in omega-3 PUFA (390-1170 mg/day according to patient weight) during two 6-month periods. RESULTS: Increase in eicosapentaenoic acid was observed in neutrophil membrane following omega-3 PUFA dietary supplementation (from 0.7+/-0.6 to 1.6+/-0.6 micromol%, P<0.01). The leukotriene B(4) (LTB(4))/leukotriene B(5) (LTB(5)) ratio was decreased (from 72+/-27 to 24+/-7, P<0.001) in CF patients taking omega-3 PUFA supplements. In contrast, omega-3 PUFA supplementation affected neither internalization of IL-8 receptors following IL-8 exposure, nor IL-8-induced neutrophil chemotaxis. CONCLUSION: Our results show that omega-3 PUFA are incorporated in neutrophil membranes. The subsequent decrease in LTB(4)/LTB(5) ratio suggests that, in such conditions, neutrophils may produce less pro-inflammatory mediators from the acid arachidonic pathway. These data indicate that omega-3 PUFA intake may have anti-inflammatory effect that still need to be assessed by long-term studies following large groups of patients. Options: A: Omega-3 supplements provide significant benefits and are recommended for routine use in cystic fibrosis patients. B: Omega-3 supplements may offer some limited benefits with relatively few adverse effects, but the evidence is insufficient to recommend routine use. C: Omega-3 supplements have no benefits and are associated with significant adverse effects, making them unsuitable for cystic fibrosis patients. D: Omega-3 supplements are harmful and should be avoided in cystic fibrosis patients.	B
4,626	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the overall conclusion regarding the efficacy and safety of interventions for managing fatigue in individuals with inflammatory bowel disease (IBD)? Please answer this question based on the information provided below: Cognitive behavioural therapy for the management of inflammatory bowel disease-fatigue with a nested qualitative element: study protocol for a randomised controlled trial. BACKGROUND: Fatigue is one of the most prevalent and burdensome symptoms for patients with inflammatory bowel disease (IBD). Although fatigue increases during periods of inflammation, for some patients it persists when disease is in remission. Compared to other long-term conditions where fatigue has been extensively researched, optimal management of fatigue in patients with IBD is unknown and fatigue has rarely been the primary outcome in intervention studies. To date, interventions for the management of IBD-fatigue are sparse, have short-term effects and have not been implemented within the existing health system. There is a need to integrate current best evidence across different conditions, patient experience and clinical expertise in order to develop interventions for IBD-fatigue management that are feasible and effective. Modifying an existing intervention for patients with multiple sclerosis, this study aims to assess the feasibility and initial estimates of efficacy of a cognitive behavioural therapy (CBT) intervention for the management of fatigue in patients with IBD. METHODS: The study will be a two-arm pilot randomised controlled trial. Patients will be recruited from one outpatient IBD clinic and randomised individually to either: Group 1 (CBT manual for the management of fatigue, one 60-min session and seven 30-min telephone/Skype sessions with a therapist over an eight-week period); or Group 2 (fatigue information sheet to use without therapist help). Self-reported IBD-fatigue (Inflammatory Bowel Disease-Fatigue Scale) and IBD-quality of life (United Kingdom Inflammatory Bowel Disease Questionnaire) and self-reported disease activity will be collected at baseline, three, six and 12 months post randomisation. Illness perceptions, daytime sleepiness, anxiety and depression explanatory variables will be collected only at three months post randomisation. Clinical and sociodemographic data will be retrieved from the patients' medical notes. A nested qualitative study will evaluate patient and therapist experience, and healthcare professionals' perceptions of the intervention. DISCUSSION: The study will provide evidence of the feasibility and initial estimates of efficacy of a CBT intervention for the management of fatigue in patients with IBD. Quantitative and qualitative findings from the study will contribute to the development and implementation of a large-scale randomised controlled trial assessing the efficacy of CBT interventions for IBD-fatigue. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN17917944 . Registered on 2 September 2016. Cognitive-behavioural therapy for the management of inflammatory bowel disease-fatigue: a feasibility randomised controlled trial. BACKGROUND: Fatigue is the third most prevalent symptom for patients with inflammatory bowel disease (IBD), yet optimal strategies for its management are unclear. Treatment protocols for fatigue in other conditions have been based on cognitive-behavioural models. Targeting cognitions, emotions and behaviour related to fatigue through cognitive-behavioural therapy (CBT) may be a viable option to improve fatigue and quality of life (QoL) in IBD. METHODS: This single centre, two-arm, feasibility randomised controlled trial (RCT) aimed to assess the feasibility and initial estimates of potential efficacy of a CBT intervention for the management of IBD-fatigue. Feasibility, acceptability and initial estimates of potential efficacy outcomes were collected through self-report measures and semi-structured interviews. Participants were recruited from one tertiary referral centre. Intervention Group 1 received a CBT manual for fatigue, one 60-min and seven 30-min telephone sessions with a therapist over 8-weeks. Control Group 2 received a fatigue information sheet without therapist support. A nested qualitative study evaluated patients' and therapists' experiences, and IBD-healthcare professionals' (HCPs) perceptions of the intervention. RESULTS: Eighty-nine participants were assessed for eligibility. Of these, 31 of the 70 eligible participants consented to participate (recruitment rate of 44%). Of the 15 participants randomised to the intervention group, 13 (87%) started it and 10 (77% of those who started) completed all 8 sessions. Follow-up questionnaires were completed by 22 (71%) participants at 3 months, 14 (45%) at 6 months and 12 (39%) at 12 months' follow-up. The intervention was acceptable to participants and feasible for therapists to deliver. HCPs reported that the intervention would be applicable, but time, finance and training constraints limit its implementation. Initial estimates of potential efficacy with complete case analysis showed a reduction in fatigue and an increase in QoL at 3, 6 and 12 months post-randomisation. CONCLUSIONS: A full-scale effectiveness RCT testing CBT for IBD-fatigue is feasible and is potentially worthwhile with some changes to the protocol. However, given the small numbers, further pilot work is warranted before a full-scale RCT. TRIAL REGISTRATION: Registration Trial ISRCTN 17917944, Registered 2 September 2016. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. BACKGROUND & AIMS: This study evaluated the efficacy and safety of adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody administered subcutaneously, in the maintenance of response and remission in patients with moderate to severe Crohn's disease (CD). METHODS: Patients received open-label induction therapy with adalimumab 80 mg (week 0) followed by 40 mg (week 2). At week 4, patients were stratified by response (decrease in Crohn's Disease Activity Index > or =70 points from baseline) and randomized to double-blind treatment with placebo, adalimumab 40 mg every other week (eow), or adalimumab 40 mg weekly through week 56. Co-primary end points were the percentages of randomized responders who achieved clinical remission (Crohn's Disease Activity Index score <150) at weeks 26 and 56. RESULTS: The percentage of randomized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 (40%, 47%, and 17%, respectively; P < .001) and week 56 (36%, 41%, and 12%, respectively; P < .001). No significant differences in efficacy between adalimumab eow and weekly were observed. More patients receiving placebo discontinued treatment because of an adverse event (13.4%) than those receiving adalimumab (6.9% and 4.7% in the 40-mg eow and 40-mg weekly groups, respectively). CONCLUSIONS: Among patients who responded to adalimumab, both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks. Adalimumab was well-tolerated, with a safety profile consistent with previous experience with the drug. Effects of adalimumab maintenance therapy on health-related quality of life of patients with Crohn's disease: patient-reported outcomes of the CHARM trial. OBJECTIVES: We evaluated the effects of adalimumab maintenance therapy on health-related quality of life (HRQOL) in patients with moderate to severe Crohn's disease. METHODS: In a Phase III, randomized, double-blind clinical trial (CHARM) of moderate to severe Crohn's disease patients, HRQOL outcomes were compared between the adalimumab maintenance treatment groups (every other week and weekly injection) and the adalimumab induction-only group. The Zung Self-Rating Depression Scale, functional assessment of chronic illness therapy (FACIT)-Fatigue, visual analog pain scales, Inflammatory Bowel Disease questionnaire (IBDQ), and Medical Outcomes Study 36-item Short Form Health Survey (SF-36) were analyzed for 499 randomized responders (a decrease of > or =70 points from baseline in the Crohn's Disease Activity Index [CDAI]) at baseline and weeks 4, 12, 26, and 56. RESULTS: CHARM patients' HRQOL was substantially impaired at baseline. Following a 4-week adalimumab induction therapy, patients experienced statistically significant improvements in all HRQOL measures (P < 0.0001). Compared with patients who were assigned to placebo after induction therapy, patients who continued adalimumab at 40 mg every other week maintenance therapy reported less depression (P < 0.01), fewer fatigue symptoms (P < 0.001), greater improvements in the IBDQ (P < 0.05), greater SF-36 physical component summary scores (P < 0.05), and less abdominal pain (P < 0.05) from weeks 12 to 56. They also had greater SF-36 mental component summary scores at week 56 (P < 0.05). Patients who continued adalimumab at 40-mg weekly maintenance therapy reported less depression and fewer fatigue symptoms at week 56, greater improvement in IBDQ, and less abdominal pain from weeks 12 to 56 (all P < 0.05 vs. placebo). CONCLUSIONS: Adalimumab maintenance therapy provided sustained improvements in HRQOL for patients with moderate to severe Crohn's disease through week 56. Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial. BACKGROUND: Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm. METHODS: CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18-75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150-450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (<70 kg or ≥70 kg), and disease duration (≤2 years or >2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 μg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of <70 points compared with baseline or CDAI >200; clinical management group after random assignment: CDAI decrease of <100 points compared with baseline or CDAI ≥200, or prednisone use in the previous week). De-escalation was possible for patients receiving weekly adalimumab and azathioprine or weekly adalimumab alone if failure criteria were not met. The primary endpoint was mucosal healing (CDEIS <4) with absence of deep ulcers 48 weeks after randomisation. Primary and safety analyses were done in the intention-to-treat population. This trial has been completed, and is registered with ClinicalTrials.gov, number NCT01235689. FINDINGS: Between Feb 11, 2011, and Nov 3, 2016, 244 patients (mean disease duration: clinical management group, 0·9 years [SD 1·7]; tight control group, 1·0 year [2·3]) were randomly assigned to monitoring groups (n=122 per group). 29 (24%) patients in the clinical management group and 32 (26%) patients in the tight control group discontinued the study, mostly because of adverse events. A significantly higher proportion of patients in the tight control group achieved the primary endpoint at week 48 (56 [46%] of 122 patients) than in the clinical management group (37 [30%] of 122 patients), with a Cochran-Mantel-Haenszel test-adjusted risk difference of 16·1% (95% CI 3·9-28·3; p=0·010). 105 (86%) of 122 patients in the tight control group and 100 (82%) of 122 patients in the clinical management group reported treatment-emergent adverse events; no treatment-related deaths occurred. The most common adverse events were nausea (21 [17%] of 122 patients), nasopharyngitis (18 [15%]), and headache (18 [15%]) in the tight control group, and worsening Crohn's disease (35 [29%] of 122 patients), arthralgia (19 [16%]), and nasopharyngitis (18 [15%]) in the clinical management group. INTERPRETATION: CALM is the first study to show that timely escalation with an anti-tumour necrosis factor therapy on the basis of clinical symptoms combined with biomarkers in patients with early Crohn's disease results in better clinical and endoscopic outcomes than symptom-driven decisions alone. Future studies should assess the effects of such a strategy on long-term outcomes such as bowel damage, surgeries, hospital admissions, and disability. FUNDING: AbbVie. Vedolizumab as induction and maintenance therapy for ulcerative colitis. BACKGROUND: Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis. METHODS: We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. RESULTS: Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P<0.001). At week 52, 41.8% of patients who continued to receive vedolizumab every 8 weeks and 44.8% of patients who continued to receive vedolizumab every 4 weeks were in clinical remission (Mayo Clinic score ≤2 and no subscore >1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P<0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P<0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups. CONCLUSIONS: Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.). A stress management programme for Crohn's disease. The present study was designed to assess the effectiveness of techniques of behavioural assessment and treatment of Crohn's disease (CD). On the assumption that stress events have a pronounced influence on the life of Crohn's patients, we proposed stress management treatment. This is intended to control stress and improve patients' personal and social competence. Forty-five patients with Crohn's disease were randomly assigned to one of three treatment groups, two experimental groups: stress management and self-directed stress management, and a control group: conventional medical treatment. The subjects underwent eight individual sessions which were specific to each condition. All subjects completed symptom monitoring diaries. The subjects who received training in stress management experienced a significant post-treatment reduction of tiredness (P < 0.1), constipation (P < 0.1), abdominal pain (P < 0.5) and distended abdomen (P < 0.5). The subjects who received training in self-directed stress management experienced a significant reduction in tiredness (P < 0.1) and abdominal pain (P < 0.5). No significant changes were observed in symptomatology in the conventional medical treatment group. Similar results were obtained in the 12 month follow-up. Ferric maltol is effective in correcting iron deficiency anemia in patients with inflammatory bowel disease: results from a phase-3 clinical trial program. BACKGROUND: Iron deficiency anemia (IDA) is frequently seen in inflammatory bowel disease. Traditionally, oral iron supplementation is linked to extensive gastrointestinal side effects and possible disease exacerbation. This multicenter phase-3 study tested the efficacy and safety of ferric maltol, a complex of ferric (Fe) iron with maltol (3-hydroxy-2-methyl-4-pyrone), as a novel oral iron therapy for IDA. METHODS: Adult patients with quiescent or mild-to-moderate ulcerative colitis or Crohn's disease, mild-to-moderate IDA (9.5-12.0 g/dL and 9.5-13.0 g/dL in females and males, respectively), and documented failure on previous oral ferrous products received oral ferric maltol capsules (30 mg twice a day) or identical placebo for 12 weeks according to a randomized, double-blind, placebo-controlled study design. The primary efficacy endpoint was change in hemoglobin (Hb) from baseline to week 12. Safety and tolerability were assessed. RESULTS: Of 329 patients screened, 128 received randomized therapy (64 ferric maltol-treated and 64 placebo-treated patients) and comprised the intent-to-treat efficacy analysis: 55 ferric maltol patients (86%) and 53 placebo patients (83%) completed the trial. Significant improvements in Hb were observed with ferric maltol versus placebo at weeks 4, 8, and 12: mean (SE) 1.04 (0.11) g/dL, 1.76 (0.15) g/dL, and 2.25 (0.19) g/dL, respectively (P < 0.0001 at all time-points; analysis of covariance). Hb was normalized in two-thirds of patients by week 12. The safety profile of ferric maltol was comparable with placebo, with no impact on inflammatory bowel disease severity. CONCLUSIONS: Ferric maltol provided rapid clinically meaningful improvements in Hb and showed a favorable safety profile, suggesting its possible use as an alternative to intravenous iron in IDA inflammatory bowel disease. Vedolizumab as induction and maintenance therapy for Crohn's disease. BACKGROUND: The efficacy of vedolizumab, an α4β7 integrin antibody, in Crohn's disease is unknown. METHODS: In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52. RESULTS: At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of ≤150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (≥100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P<0.001 and P=0.004 for the two vedolizumab groups, respectively, vs. placebo). Antibodies against vedolizumab developed in 4.0% of the patients. Nasopharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving vedolizumab than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%). CONCLUSIONS: Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolizumab (rather than switching to placebo) were more likely to be in remission at week 52. Adverse events were more common with vedolizumab. (Funded by Millennium Pharmaceuticals; GEMINI 2 ClinicalTrials.gov number, NCT00783692.). Effect of a Medicinal Agaricus blazei Murill-Based Mushroom Extract, AndoSan™, on Symptoms, Fatigue and Quality of Life in Patients with Ulcerative Colitis in a Randomized Single-Blinded Placebo Controlled Study. BACKGROUND: Ingestion of AndoSan™, based on the mushroom Agaricus blazei Murill, has previously been shown to exhibit anti-inflammatory effects because of reduction of pro-inflammatory cytokines in healthy individuals and patients with ulcerative colitis. In this randomized single-blinded placebo controlled study we examined whether intake of AndoSan™ also resulted in clinical effects. METHODS AND FINDINGS: 50 patients with symptomatic ulcerative colitis were block-randomized and blinded for oral daily intake of AndoSan™ or placebo for the 21 days' experimental period. The patients reported scores for symptoms, fatigue and health related quality of life (HRQoL) at days 0, 14 and 21. Fecal calprotectin and general blood parameters were also analyzed. In the AndoSan™ group (n = 24) symptoms improved from baseline (day 0) to days 14 and 21, with respective mean scores (95% CI) of 5.88 (4.92-6.83), 4.71 (3.90-5.52) (p = 0.002) and 4.50 (3.70-5.30) (p = 0.001). Corresponding improved mean scores (±SD) for total fatigue were 16.6 (5.59), 14.1 (4.50) (p = 0.001) and 15.1 (4.09) (p = 0.023). These scores in the placebo group (n = 26) were not improved. When comparing the two study groups using mixed model statistics, we found significant better scores for the AndoSan™-patients. HRQoL for dimensions bodily pain, vitality, social functioning and mental health improved in the AndoSan™ group. There were no alterations in general blood samples and fecal calprotectin. CONCLUSIONS: Beneficiary effects on symptoms, fatigue and HRQoL from AndoSan™ consumption were demonstrated in this per-protocol study, supporting its use as a supplement to conventional medication for patients with mild to moderate symptoms from ulcerative colitis. The patients did not report any harms or unintended effects of AndoSan™ in this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT01496053. Effect of the Medicinal Agaricus blazei Murill-Based Mushroom Extract, AndoSanTM, on Symptoms, Fatigue and Quality of Life in Patients with Crohn's Disease in a Randomized Single-Blinded Placebo Controlled Study. BACKGROUND: Ingestion of AndoSanTM, based on the mushroom Agaricus blazei Murill, has previously shown an anti-inflammatory effect through reduction of pro-inflammatory cytokines in healthy individuals and patients with Crohn's disease (CD). In this randomized single-blinded placebo-controlled study we examined whether intake of AndoSanTM also resulted in clinical effects. METHODS AND FINDINGS: 50 patients with symptomatic CD were randomized for oral daily consumption of AndoSanTM or placebo for a 21-day experimental period, in this per-protocol study. Patients reported validated scores for symptoms, fatigue and health related quality of life (HRQoL) at days 0, 14 and 21. Fecal calprotectin and general blood parameters were also analyzed. In the AndoSanTM group (n = 25) symptoms improved from baseline (day 0) to days 14 and 21, with respective mean scores (95% CI) of 5.52 (4.64-6.40), 4.48 (3.69-5.27) and 4.08 (3.22-4.94) (p<0,001). We found significant improvements in symptom score for both genders in the AndoSanTM group, and no significant changes in the placebo (n = 25) group. There were however no significant differences between the groups (p = 0.106), although a marginal effect in symptom score for men (p = 0.054). There were comparable improvements in physical, mental and total fatigue for both groups. HRQoL versus baseline were at day 21 improved for bodily pain and vitality in the AndoSanTM group and for vitality and social functioning in the placebo group. No crucial changes in general blood samples and fecal calprotectin were detected. CONCLUSIONS: The results from this single-blinded randomized clinical trial shows significant improvement on symptoms, for both genders, in the AndoSanTM group, but no significant differences between the study groups. The results on fatigue, HRQoL, fecal calprotectin and blood samples were quite similar compared with placebo. The patients did not report any harms or unintended effects of AndoSanTM. CD patients with mild to moderate symptoms may have beneficiary effects of AndoSanTM as a safe supplement in addition to conventional medication. TRIAL REGISTRATION: ClinicalTrials.gov NCT01496053. Fatigue management in patients with IBD: a randomised controlled trial. OBJECTIVE: To assess the effectiveness of solution-focused therapy (SFT) on fatigue and quality of life (QoL) in patients with fatigued inflammatory bowel disease (IBD). DESIGN: Randomised controlled trial in two Dutch hospitals. Patients with IBD with quiescent IBD and with a Checklist Individual Strength--Fatigue (CIS--fatigue) score of ≥ 35 were enrolled. Patients were 1:1 randomised to receive SFT or care as usual (CAU) for 3 months. Patients were followed for a further 6 months after the SFT. Primary endpoint was defined as changes in fatigue and QoL during follow-up. Secondary endpoints included change in anxiety and depression, medication use, side effects to medication, disease activity, laboratory parameters (C-reactive protein, leucocytes and haemoglobin) and sleep quality. RESULTS: Ninety-eight patients were included, of whom 63% were women, mean age was 40.1 years. After the SFT course, 17 (39%) patients in the SFT group had a CIS-fatigue score below 35 compared with eight (18%) of patients in the CAU group (p=0.03). The SFT group also showed a greater reduction in fatigue across the first 6 months compared with the CAU group (CIS-fatigue: p=<0.001 and CIS-total: p=0.001). SFT was associated with a significant higher mean IBD questionnaire change at 3 months (p=0.020). At 9 months, no significant differences between the two groups were observed. CONCLUSIONS: SFT has a significant beneficial effect on the severity of fatigue and QoL in patients with quiescent IBD. However, this effect diminished during follow-up. Options: A: The effects of interventions for managing fatigue in IBD are well-established and show significant benefits. B: The effects of interventions for managing fatigue in IBD are uncertain, and no firm conclusions can be drawn. C: Pharmacological interventions are proven to be effective, while non-pharmacological interventions are not. D: Non-pharmacological interventions are proven to be effective, while pharmacological interventions are not.	B
4,627	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the conclusion regarding the effectiveness and safety of non-invasive respiratory support for managing transient tachypnea of the newborn? Please answer this question based on the information provided below: Nasal intermittent mandatory ventilation versus nasal continuous positive airway pressure for transient tachypnea of newborn: a randomized, prospective study. OBJECTIVE: To evaluate the efficacy of nasal intermittent mandatory ventilation (NIMV) in reducing the duration of respiratory distress compared with nasal continuous positive airway pressure (NCPAP) in transient tachypnea of the newborn (TTN). PATIENT AND METHODS: In this randomized-prospective study, 40 infants with a gestational age ≥ 37 weeks and birth weight ≥ 2000 g with TTN were randomized to either nonsynchronized NIMV (n = 20) or NCPAP (n = 20). The primary end point was the reduction of the duration of respiratory distress. Secondary end points were the duration and level of oxygen supplementation, the incidence of complications such as pneumothorax, pneumonia and respiratory failure requiring entubation. RESULTS: There were no significant difference in the duration of respiratory support (28.0 ± 19.2 h versus 32.2 ± 23.3 h, p = 0.231), O2 therapy (31.2 ± 15.6 h versus 29.0 ± 19.3 h, p = 0.187), duration of TTN (67.6 ± 36.5 h versus 63.3 ± 39.1 h, p = 0.480) and hospitalization (6.2 ± 2.6 d versus 5.4 ± 2.0 d, p = 0.330) between the groups. The rate of complications were not significantly different between the groups. CONCLUSION: Our study indicates that NIMV is well tolerated and as effective as NCPAP in the treatment of TTN. Nasal high frequency percussive ventilation versus nasal continuous positive airway pressure in transient tachypnea of the newborn: a pilot randomized controlled trial (NCT00556738). OBJECTIVE: To determine whether nasal high frequency percussive ventilation (NHFPV) would decrease duration of transient tachypnea of the newborn (TTN) compared to nasal continuous positive airway pressure (NCPAP) in newborn infants. METHODS: A prospective, unmasked, randomized, controlled clinical trial was conducted in 46 eligible newborn infants who were hospitalized for TTN in the University Hospital of Bordeaux (France) between 2007 and 2009. Infants born by cesarian section ≥37 GA, ≥2,000 g with diagnosis of TTN and with a transcutaneous saturation <90% at 20 min after birth were eligible. Infants were randomized to either NHFPV or NCPAP. The primary endpoint was a reduction of the duration of TTN. Secondary endpoints were the duration of oxygen therapy and the minimal level required to obtain a saturation between 90% and 96% integrated into an index which included a time factor: [(FiO2 -21)/time of O2 therapy]. RESULTS: In the NHFPV group the duration of TTN was half the time of NCPAP group (105 min ± 20 and 377 min ± 150, respectively; P < 0.0001). There was a significant decrease in duration of oxygen supplementation in the NHFPV group (6.3 min ± 3.3) compared to the NCPAP group (19.1 min ± 8.1; P < 0.001), and a significant decrease in level of oxygen supplementation [(FiO2 -0.21)/time of O2 therapy] in the NHFPV group (0.29 min(-1) ± 0.16) compared to the NCPAP group (0.46 min(-1) ± 0.50; P < 0.001). There was no complication and NHFPV was as well tolerated as NCPAP. CONCLUSION: NHFPV is well tolerated and more effective than NCPAP in treatment of TTN. NHFPV might be a novel and safe tool to manage TTN. Pediatr Pulmonol. Early rescue Neopuff for infants with transient tachypnea of newborn: a randomized controlled trial. OBJECTIVE: To examine the efficacy of early continuous positive airway pressure (CPAP), delivered using a T-piece-based infant resuscitator (Neopuff) via a face mask, in reducing the severity and duration of transient tachypnea of the newborn (TTN) as well as testing a hypothesis suggesting that rapid clearance of fetal lung fluid to the circulation via CPAP would increase plasma B-type natriuretic peptide (BNP). METHODS: A randomized controlled trial (NCT01859533) was conducted on 64 late preterm/term neonates, delivered by cesarean section and presented by respiratory distress shortly after birth. The Neopuff group included 34 neonates received 20 min of early CPAP and control group included 30 neonates received free flow O RESULTS: The duration of tachypnea was shorter in Neopuff group with less need of neonatal intensive care unit admission and need of mechanical support (p < .05) with no effect on duration of hospitalization (p > .05). Plasma BNP showed no significant difference between pre- and post-Neopuff levels (p > .05). A positive correlation was found between BNP and duration of tachypnea as well as the length of hospitalization (p < .05) among Neopuff group. CONCLUSION: Early rescue CPAP reduces the duration and severity of respiratory distress among infants with TTN. Options: A: Non-invasive respiratory support significantly reduces the need for mechanical ventilation and the incidence of pneumothorax. B: Non-invasive respiratory support significantly increases the duration of tachypnea in newborns. C: There is insufficient evidence to establish the benefit and harms of non-invasive respiratory support in the management of transient tachypnea of the newborn. D: Non-invasive respiratory support is proven to be safe and effective for the treatment of transient tachypnea of the newborn.	C
4,628	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the effect of vitamin D, calcium, or a combination of vitamin D and calcium on the healing of nutritional rickets in children? Please answer this question based on the information provided below: Management of nutritional rickets in Indian children: a randomized controlled trial. INTRODUCTION: Rickets is usually attributed to vitamin D deficiency. However, recent studies have implicated dietary calcium deficiency in its etiology. Information on relative efficacy of calcium, vitamin D or both together in healing of rickets is limited. OBJECTIVE: To study effect of treatment with calcium, vitamin D or a combination of these two on healing of nutritional rickets in young children. DESIGN: Randomized controlled trial. METHODS: Sixty-seven cases of nutritional rickets in the age group of 6 months to 5 years were randomly allocated to receive vitamin D (600 000 IU single intramuscular dose), calcium (75 mg/kg/day elemental calcium orally) or a combination of the above two for a period of 12 weeks. The demographic parameters, nutritional status, dietary calcium and phytate intake were assessed for all. Radiographs (wrist and knee) and biochemical parameters (serum calcium, inorganic phosphate, alkaline phosphatase, 25-hydroxycholecalciferol and parathyroid hormone) were evaluated at baseline, 6 and 12 weeks for evidence of healing. RESULTS: Mean dietary intake of calcium in all cases was low (204 ± 129 mg/day). Mean serum 25-hydroxycholecalciferol D level was 15.9 ± 12.4 ng/ml, and 82.1% of patients had serum vitamin D levels <20 ng/ml, indicative of vitamin D deficiency. After 6 and 12 weeks of treatment, radiological and biochemical evidence of healing rickets was observed in all treatment groups, albeit to a variable extent. The combined end point of normal serum alkaline phosphatase and complete radiological healing at 12 weeks was observed in 50% subjects on combination therapy as compared with 15.7% subjects on vitamin D alone and 11.7% on calcium alone. CONCLUSIONS: Children with rickets had a low serum vitamin D level and a low dietary calcium intake. The best therapeutic response was seen with a combination of vitamin D and calcium than either of them given alone. TRIAL REGISTRATION NUMBER: CTRI/2010/091/000448. Varying role of vitamin D deficiency in the etiology of rickets in young children vs. adolescents in northern India. The relative importance of calcium vs. vitamin D deficiency in the etiology of nutritional rickets in the tropics may be different in children compared with adolescents. We studied calcium intake, sun exposure, serum alkaline phosphatase, and 25 hydroxyvitamin D in 24 children and 16 adolescents with rickets/osteomalacia. The values were compared with those obtained in control subjects (34 children and 19 adolescents). We found that young children with rickets had lower calcium intake compared with controls (285 +/- 113 vs. 404 +/- 149 mg/day, p < 0.01), but similar sun exposure (55 +/- 28 vs. 56 +/- 23 min x m2/day) and 25 hydroxyvitamin D (49 +/- 38 vs. 61 +/- 36 nmol/l). Sixteen of 24 children with rickets had 25 hydroxyvitamin D above the rachitic range (> 25 nmol/l), in contrast to one of 16 adolescents. Adolescent patients had low calcium intake vs. controls (305 +/- 196 vs. 762 +/- 183 mg, p < 0.001), and lower sunshine exposure (16 +/- 15 vs. 27 +/- 17 min x m2/day, p < 0.01) and serum 25 hydroxyvitamin D (12.6 +/- 7.1 vs. 46 +/- 45.4 nmol/l, p < 0.001). The odds ratio for developing rickets with a daily calcium intake below 300 mg was 4.8 (95 per cent CI, 1.9 - 12.4, p = 0.001). Subjects with rickets were randomized to receive 1 g calcium daily, with or without vitamin D. Children showed complete healing in 3 months, whether they received calcium alone or with vitamin D. Adolescents showed no response to calcium alone, but had complete healing with calcium and vitamin D in 3-9 months (mean 5.3 months). Thus deficient calcium intake is universal among children and adolescents with rickets/osteomalacia. Inadequate sun exposure and vitamin D deficiency are important in the etiology of adolescent osteomalacia. A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children. BACKGROUND: Nutritional rickets remains prevalent in many tropical countries despite the fact that such countries have ample sunlight. Some postulate that a deficiency of dietary calcium, rather than vitamin D, is often responsible for rickets after infancy. METHODS: We enrolled 123 Nigerian children (median age, 46 months) with rickets in a randomized, double-blind, controlled trial of 24 weeks of treatment with vitamin D (600,000 U intramuscularly at enrollment and at 12 weeks), calcium (1000 mg daily), or a combination of vitamin D and calcium. We compared the calcium intake of the children at enrollment with that of control children without rickets who were matched for sex, age, and weight. We measured serum calcium and alkaline phosphatase and used a 10-point radiographic score to assess the response to treatment at 24 weeks. RESULTS: The daily dietary calcium intake was low in the children with rickets and the control children (median, 203 mg and 196 mg, respectively; P=0.64). Treatment produced a smaller increase in the mean (+/-SD) serum calcium concentration in the vitamin D group (from 7.8+/-0.8 mg per deciliter [2.0+/-0.2 mmol per liter] at base line to 8.3+/-0.7 mg per deciliter [2.1+/-0.2 mmol per liter] at 24 weeks) than in the calcium group (from 7.5+/-0.8 [1.9+/-0.2 mmol per liter] to 9.0+/-0.6 mg per deciliter [2.2+/-0.2 mmol per liter], P<0.001) or the combination-therapy group (from 7.7+/-1.0 [1.9+/-0.25 mmol per liter] to 9.1+/-0.6 mg per deciliter [2.3+/-0.2 mmol per liter], P<0.001). A greater proportion of children in the calcium and combination-therapy groups than in the vitamin D group reached the combined end point of a serum alkaline phosphatase concentration of 350 U per liter or less and radiographic evidence of nearly complete healing of rickets (61 percent, 58 percent, and 19 percent, respectively; P<0.001). CONCLUSIONS: Nigerian children with rickets have a low intake of calcium and have a better response to treatment with calcium alone or in combination with vitamin D than to treatment with vitamin D alone. Vitamin D treatment in calcium-deficiency rickets: a randomised controlled trial. OBJECTIVE: To determine whether children with calcium-deficiency rickets have a better response to treatment with vitamin D and calcium than with calcium alone. DESIGN: Randomised controlled trial. SETTING: Jos University Teaching Hospital, Jos, Nigeria. POPULATION: Nigerian children with active rickets treated with calcium carbonate as limestone (approximately 938 mg elemental calcium twice daily) were, in addition, randomised to receive either oral vitamin D2 50,000 IU (Ca+D, n=44) or placebo (Ca, n=28) monthly for 24 weeks. MAIN OUTCOME MEASURE: Achievement of a 10-point radiographic severity score ≤1.5 and serum alkaline phosphatase ≤350 U/L. RESULTS: The median (range) age of enrolled children was 46 (15-102) months, and baseline characteristics were similar in the two groups. Mean (±SD) 25-hydroxyvitamin D (25(OH)D) was 30.2±13.2 nmol/L at baseline, and 29 (43%) had values <30 nmol/L. Baseline alkaline phosphatase and radiographic scores were unrelated to vitamin D status. Of the 68 children (94% of original cohort) who completed 24 weeks of treatment, 29 (67%) in the Ca+D group and 11 (44%) in the Ca group achieved the primary outcome (p=0.06). Baseline 25(OH)D did not alter treatment group effects (p=0.99 for interaction). At the end of 24 weeks, 25(OH)D values were 55.4±17.0 nmol/L and 37.9±20.0 nmol/L in the Ca+D and Ca groups, respectively, (p<0.001). In the Ca+D and Ca groups, the final 25(OH)D concentration was greater in those who achieved the primary outcome (56.4±17.2 nmol/L) than in those who did not (37.7±18.5 nmol/L, p<0.001). CONCLUSIONS: In children with calcium-deficiency rickets, there is a trend for vitamin D to improve the response to treatment with calcium carbonate as limestone, independent of baseline 25(OH)D concentrations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00949832. Options: A: Vitamin D alone is more effective than calcium alone in improving the healing of nutritional rickets. B: Calcium alone is more effective than vitamin D alone in improving the healing of nutritional rickets. C: A combination of vitamin D and calcium is more effective than vitamin D alone in improving the healing of nutritional rickets. D: There is no difference in the effectiveness of vitamin D, calcium, or a combination of vitamin D and calcium in improving the healing of nutritional rickets.	C
4,629	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What are the potential benefits and limitations of disease-modifying pharmacological agents for transthyretin-related familial amyloid polyneuropathy (TTR-FAP) based on recent clinical trials? Please answer this question based on the information provided below: Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. BACKGROUND: Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin. METHODS: In this phase 3 trial, we randomly assigned patients with hereditary transthyretin amyloidosis with polyneuropathy, in a 2:1 ratio, to receive intravenous patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks. The primary end point was the change from baseline in the modified Neuropathy Impairment Score+7 (mNIS+7; range, 0 to 304, with higher scores indicating more impairment) at 18 months. Other assessments included the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire (range, -4 to 136, with higher scores indicating worse quality of life), 10-m walk test (with gait speed measured in meters per second), and modified body-mass index (modified BMI, defined as [weight in kilograms divided by square of height in meters]×albumin level in grams per liter; lower values indicated worse nutritional status). RESULTS: A total of 225 patients underwent randomization (148 to the patisiran group and 77 to the placebo group). The mean (±SD) mNIS+7 at baseline was 80.9±41.5 in the patisiran group and 74.6±37.0 in the placebo group; the least-squares mean (±SE) change from baseline was -6.0±1.7 versus 28.0±2.6 (difference, -34.0 points; P<0.001) at 18 months. The mean (±SD) baseline Norfolk QOL-DN score was 59.6±28.2 in the patisiran group and 55.5±24.3 in the placebo group; the least-squares mean (±SE) change from baseline was -6.7±1.8 versus 14.4±2.7 (difference, -21.1 points; P<0.001) at 18 months. Patisiran also showed an effect on gait speed and modified BMI. At 18 months, the least-squares mean change from baseline in gait speed was 0.08±0.02 m per second with patisiran versus -0.24±0.04 m per second with placebo (difference, 0.31 m per second; P<0.001), and the least-squares mean change from baseline in the modified BMI was -3.7±9.6 versus -119.4±14.5 (difference, 115.7; P<0.001). Approximately 20% of the patients who received patisiran and 10% of those who received placebo had mild or moderate infusion-related reactions; the overall incidence and types of adverse events were similar in the two groups. CONCLUSIONS: In this trial, patisiran improved multiple clinical manifestations of hereditary transthyretin amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO ClinicalTrials.gov number, NCT01960348 .). Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy. BACKGROUND: Patisiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of hereditary ATTR (hATTR) amyloidosis, a progressive disease associated with significant disability, morbidity, and mortality. METHODS: Here we describe the rationale and design of the Phase 3 APOLLO study, a randomized, double-blind, placebo-controlled, global study to evaluate the efficacy and safety of patisiran in patients with hATTR amyloidosis with polyneuropathy. Eligible patients are 18-85 years old with hATTR amyloidosis, investigator-estimated survival of ≥2 years, Neuropathy Impairment Score (NIS) of 5-130, and polyneuropathy disability score ≤IIIb. Patients are randomized 2:1 to receive either intravenous patisiran 0.3 mg/kg or placebo once every 3 weeks. The primary objective is to determine the efficacy of patisiran at 18 months based on the difference in the change in modified NIS+7 (a composite measure of motor strength, sensation, reflexes, nerve conduction, and autonomic function) between the patisiran and placebo groups. Secondary objectives are to evaluate the effect of patisiran on Norfolk-Diabetic Neuropathy quality of life questionnaire score, nutritional status (as evaluated by modified body mass index), motor function (as measured by NIS-weakness and timed 10-m walk test), and autonomic symptoms (as measured by the Composite Autonomic Symptom Score-31 questionnaire). Exploratory objectives include assessment of cardiac function and pathologic evaluation to assess nerve fiber innervation and amyloid burden. Safety of patisiran will be assessed throughout the study. DISCUSSION: APOLLO represents the largest randomized, Phase 3 study to date in patients with hATTR amyloidosis, with endpoints that capture the multisystemic nature of this disease. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov ( NCT01960348 ); October 9, 2013. Effects of Patisiran, an RNA Interference Therapeutic, on Cardiac Parameters in Patients With Hereditary Transthyretin-Mediated Amyloidosis. BACKGROUND: Hereditary transthyretin-mediated (hATTR) amyloidosis is a rapidly progressive, multisystem disease that presents with cardiomyopathy or polyneuropathy. The APOLLO study assessed the efficacy and tolerability of patisiran in patients with hATTR amyloidosis. The effects of patisiran on cardiac structure and function in a prespecified subpopulation of patients with evidence of cardiac amyloid involvement at baseline were assessed. METHODS: APOLLO was an international, randomized, double-blind, placebo-controlled phase 3 trial in patients with hATTR amyloidosis. Patients were randomized 2:1 to receive 0.3 mg/kg patisiran or placebo via intravenous infusion once every 3 weeks for 18 months. The prespecified cardiac subpopulation comprised patients with a baseline left ventricular wall thickness ≥13 mm and no history of hypertension or aortic valve disease. Prespecified exploratory cardiac end points included mean left ventricular wall thickness, global longitudinal strain, and N-terminal prohormone of brain natriuretic peptide. Cardiac parameters in the overall APOLLO patient population were also evaluated. A composite end point of cardiac hospitalizations and all-cause mortality was assessed in a post hoc analysis. RESULTS: In the cardiac subpopulation (n=126; 56% of total population), patisiran reduced mean left ventricular wall thickness (least-squares mean difference ± SEM: -0.9±0.4 mm, P=0.017), interventricular septal wall thickness, posterior wall thickness, and relative wall thickness at month 18 compared with placebo. Patisiran also led to increased end-diastolic volume (8.3±3.9 mL, P=0.036), decreased global longitudinal strain (-1.4±0.6%, P=0.015), and increased cardiac output (0.38±0.19 L/min, P=0.044) compared with placebo at month 18. Patisiran lowered N-terminal prohormone of brain natriuretic peptide at 9 and 18 months (at 18 months, ratio of fold-change patisiran/placebo 0.45, P<0.001). A consistent effect on N-terminal prohormone of brain natriuretic peptide at 18 months was observed in the overall APOLLO patient population (n=225). Median follow-up duration was 18.7 months. The exposure-adjusted rates of cardiac hospitalizations and all-cause death were 18.7 and 10.1 per 100 patient-years in the placebo and patisiran groups, respectively (Andersen-Gill hazard ratio, 0.54; 95% CI, 0.28-1.01). CONCLUSIONS: Patisiran decreased mean left ventricular wall thickness, global longitudinal strain, N-terminal prohormone of brain natriuretic peptide, and adverse cardiac outcomes compared with placebo at month 18, suggesting that patisiran may halt or reverse the progression of the cardiac manifestations of hATTR amyloidosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01960348. Patisiran Pharmacokinetics, Pharmacodynamics, and Exposure-Response Analyses in the Phase 3 APOLLO Trial in Patients With Hereditary Transthyretin-Mediated (hATTR) Amyloidosis. Hereditary transthyretin-mediated (hATTR) amyloidosis is an inherited, rapidly progressive, life-threatening disease caused by deposition of abnormal transthyretin protein. Patisiran is an RNA interference therapeutic comprising a novel, small interfering ribonucleic acid (ALN-18328) formulated in a lipid nanoparticle targeted to inhibit hepatic transthyretin protein synthesis. The lipid nanoparticle also contains 2 novel lipid excipients (DLin-MC3-DMA and PEG Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. BACKGROUND: Hereditary transthyretin amyloidosis is caused by pathogenic single-nucleotide variants in the gene encoding transthyretin ( TTR) that induce transthyretin misfolding and systemic deposition of amyloid. Progressive amyloid accumulation leads to multiorgan dysfunction and death. Inotersen, a 2'- O-methoxyethyl-modified antisense oligonucleotide, inhibits hepatic production of transthyretin. METHODS: We conducted an international, randomized, double-blind, placebo-controlled, 15-month, phase 3 trial of inotersen in adults with stage 1 (patient is ambulatory) or stage 2 (patient is ambulatory with assistance) hereditary transthyretin amyloidosis with polyneuropathy. Patients were randomly assigned, in a 2:1 ratio, to receive weekly subcutaneous injections of inotersen (300 mg) or placebo. The primary end points were the change in the modified Neuropathy Impairment Score+7 (mNIS+7; range, -22.3 to 346.3, with higher scores indicating poorer function; minimal clinically meaningful change, 2 points) and the change in the score on the patient-reported Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) questionnaire (range, -4 to 136, with higher scores indicating poorer quality of life). A decrease in scores indicated improvement. RESULTS: A total of 172 patients (112 in the inotersen group and 60 in the placebo group) received at least one dose of a trial regimen, and 139 (81%) completed the intervention period. Both primary efficacy assessments favored inotersen: the difference in the least-squares mean change from baseline to week 66 between the two groups (inotersen minus placebo) was -19.7 points (95% confidence interval [CI], -26.4 to -13.0; P<0.001) for the mNIS+7 and -11.7 points (95% CI, -18.3 to -5.1; P<0.001) for the Norfolk QOL-DN score. These improvements were independent of disease stage, mutation type, or the presence of cardiomyopathy. There were five deaths in the inotersen group and none in the placebo group. The most frequent serious adverse events in the inotersen group were glomerulonephritis (in 3 patients [3%]) and thrombocytopenia (in 3 patients [3%]), with one death associated with one of the cases of grade 4 thrombocytopenia. Thereafter, all patients received enhanced monitoring. CONCLUSIONS: Inotersen improved the course of neurologic disease and quality of life in patients with hereditary transthyretin amyloidosis. Thrombocytopenia and glomerulonephritis were managed with enhanced monitoring. (Funded by Ionis Pharmaceuticals; NEURO-TTR ClinicalTrials.gov number, NCT01737398 .). Hereditary transthyretin amyloidosis: baseline characteristics of patients in the NEURO-TTR trial. BACKGROUND: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations. OBJECTIVE: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis. METHODS: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial ( www.clinicaltrials.gov , NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed. RESULTS: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity. CONCLUSIONS: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems. The diflunisal trial: update on study drug tolerance and disease progression. The diflunisal trial: update on study drug tolerance and disease progression. Repurposing diflunisal for familial amyloid polyneuropathy: a randomized clinical trial. IMPORTANCE: Familial amyloid polyneuropathy, a lethal genetic disease caused by aggregation of variant transthyretin, induces progressive peripheral nerve deficits and disability. Diflunisal, a nonsteroidal anti-inflammatory agent, stabilizes transthyretin tetramers and prevents amyloid fibril formation in vitro. OBJECTIVE: To determine the effect of diflunisal on polyneuropathy progression in patients with familial amyloid polyneuropathy. DESIGN, SETTING, AND PARTICIPANTS: International randomized, double-blind, placebo-controlled study conducted among 130 patients with familial amyloid polyneuropathy exhibiting clinically detectable peripheral or autonomic neuropathy at amyloid centers in Sweden (Umeå), Italy (Pavia), Japan (Matsumoto and Kumamoto), England (London), and the United States (Boston, Massachusetts; New York, New York; and Rochester, Minnesota) from 2006 through 2012. INTERVENTION: Participants were randomly assigned to receive diflunisal, 250 mg (n=64), or placebo (n=66) twice daily for 2 years. MAIN OUTCOMES AND MEASURES: The primary end point, the difference in polyneuropathy progression between treatments, was measured by the Neuropathy Impairment Score plus 7 nerve tests (NIS+7) which ranges from 0 (no neurological deficits) to 270 points (no detectable peripheral nerve function). Secondary outcomes included a quality-of-life questionnaire (36-Item Short-Form Health Survey [SF-36]) and modified body mass index. Because of attrition, we used likelihood-based modeling and multiple imputation analysis of baseline to 2-year data. RESULTS: By multiple imputation, the NIS+7 score increased by 25.0 (95% CI, 18.4-31.6) points in the placebo group and by 8.7 (95% CI, 3.3-14.1) points in the diflunisal group, a difference of 16.3 points (95% CI, 8.1-24.5 points; P < .001). Mean SF-36 physical scores decreased by 4.9 (95% CI, -7.6 to -2.2) points in the placebo group and increased by 1.5 (95% CI, -0.8 to 3.7) points in the diflunisal group (P < .001). Mean SF-36 mental scores declined by 1.1 (95% CI, -4.3 to 2.0) points in the placebo group while increasing by 3.7 (95% CI, 1.0-6.4) points in the diflunisal group (P = .02). By responder analysis, 29.7% of the diflunisal group and 9.4% of the placebo group exhibited neurological stability at 2 years (<2-point increase in NIS+7 score; P = .007). CONCLUSIONS AND RELEVANCE: Among patients with familial amyloid polyneuropathy, the use of diflunisal compared with placebo for 2 years reduced the rate of progression of neurological impairment and preserved quality of life. Although longer-term follow-up studies are needed, these findings suggest benefit of this treatment for familial amyloid polyneuropathy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00294671. The Diflunisal Trial: study accrual and drug tolerance. Familial amyloidotic polyneuropathy (FAP) is a protein folding disorder that induces neuropathy and cardiomyopathy, leading to death within 7-15 years after onset of clinical disease. In vitro, small ligands binding the thyroid hormone docking site stabilize tetrameric transthyretin, inhibiting amyloid fibril formation. We undertook a randomized, placebo-controlled clinical trial to determine whether diflunisal, a well-known non-steroidal anti-inflammatory drug (NSAID) alters neurologic disease progression in FAP. We enrolled 130 subjects with wide age and FAP mutation representation. To date, few recognized complications of NSAIDs have occurred in the study cohort. Data collection will be completed by November 2012. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial. OBJECTIVES: To evaluate the efficacy and safety of 18 months of tafamidis treatment in patients with early-stage V30M transthyretin familial amyloid polyneuropathy (TTR-FAP). METHODS: In this randomized, double-blind trial, patients received tafamidis 20 mg QD or placebo. Coprimary endpoints were the Neuropathy Impairment Score-Lower Limbs (NIS-LL) responder analysis (<2-point worsening) and treatment-group difference in the mean change from baseline in Norfolk Quality of Life-Diabetic Neuropathy total score (TQOL) in the intent-to-treat (ITT) population (n = 125). These endpoints were also evaluated in the efficacy-evaluable (EE; n = 87) population. Secondary endpoints, including changes in neurologic function, nutritional status, and TTR stabilization, were analyzed in the ITT population. RESULTS: There was a higher-than-anticipated liver transplantation dropout rate. No differences were observed between the tafamidis and placebo groups for the coprimary endpoints, NIS-LL responder analysis (45.3% vs 29.5% responders; p = 0.068) and change in TQOL (2.0 vs 7.2; p = 0.116) in the ITT population. In the EE population, significantly more tafamidis patients than placebo patients were NIS-LL responders (60.0% vs 38.1%; p = 0.041), and tafamidis patients had better-preserved TQOL (0.1 vs 8.9; p = 0.045). Significant differences in most secondary endpoints favored tafamidis. TTR was stabilized in 98% of tafamidis and 0% of placebo patients (p < 0.0001). Adverse events were similar between groups. CONCLUSIONS: Although the coprimary endpoints were not met in the ITT population, tafamidis was associated with no trend toward more NIS-LL responders and a significant reduction in worsening of most neurologic variables, supporting the hypothesis that preventing TTR dissociation can delay peripheral neurologic impairment. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that 20 mg tafamidis QD was associated with no difference in clinical progression in patients with TTR-FAP, as measured by the NIS-LL and the Norfolk QOL-DN score. Secondary outcomes demonstrated a significant delay in peripheral neurologic impairment with tafamidis, which was well tolerated over 18 months. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial. BACKGROUND: Tafamidis, a non-NSAID highly specific transthyretin stabilizer, delayed neurologic disease progression as measured by Neuropathy Impairment Score-Lower Limbs (NIS-LL) in an 18-month, double-blind, placebo-controlled randomized trial in 128 patients with early-stage transthyretin V30M familial amyloid polyneuropathy (ATTRV30M-FAP). The current post hoc analyses aimed to further evaluate the effects of tafamidis in delaying ATTRV30M-FAP progression in this trial. METHODS: Pre-specified, repeated-measures analysis of change from baseline in NIS-LL in this trial (ClinicalTrials.gov NCT00409175) was repeated with addition of baseline as covariate and multiple imputation analysis for missing data by treatment group. Change in NIS-LL plus three small-fiber nerve tests (NIS-LL + Σ3) and NIS-LL plus seven nerve tests (NIS-LL + Σ7) were assessed without baseline as covariate. Treatment outcomes over the NIS-LL, Σ3, Σ7, modified body mass index and Norfolk Quality of Life-Diabetic Neuropathy Total Quality of Life Score were also examined using multivariate analysis techniques. RESULTS: Neuropathy progression based on NIS-LL change from baseline to Month 18 remained significantly reduced for tafamidis versus placebo in the baseline-adjusted and multiple imputation analyses. NIS-LL + Σ3 and NIS-LL + Σ7 captured significant treatment group differences. Multivariate analyses provided strong statistical evidence for a superior tafamidis treatment effect. CONCLUSIONS: These supportive analyses confirm that tafamidis delays neurologic progression in early-stage ATTRV30M-FAP. TRIAL REGISTRATION NUMBER: NCT00409175. Post hoc analysis of nutritional status in patients with transthyretin familial amyloid polyneuropathy: impact of tafamidis. INTRODUCTION: Gastrointestinal symptoms are common among patients with transthyretin familial amyloid polyneuropathy (TTR-FAP). This post hoc analysis evaluated the nutritional status of TTR-FAP patients treated with tafamidis while enrolled in clinical trials. METHODS: Nutritional status was measured by the modified body mass index (mBMI = BMI × albumin level). Treatment-related changes in mBMI were reported for 71 Val30Met TTR-FAP patients who completed an 18-month, randomized, double-blind, placebo-controlled trial and who continued into its open-label, 12-month extension. RESULTS: At month 18, mBMI worsened in the placebo group (n = 33) (-33 ± 16 kg/m(2) g/l, P = 0.04 versus baseline) but improved in the tafamidis group (n = 38) (+37 ± 14 kg/m(2) g/l, P = 0.01 versus baseline) such that the effect size between the groups was statistically significant (P = 0.001). By month 30 (completion of the open-label extension), placebo patients with 12 months of tafamidis treatment and tafamidis-treated patients with 30 months of treatment both tended to increase their mBMI (28 ± 19 kg/m(2) g/l and 16 ± 18 kg/m(2) g/l, respectively). Increase in BMI was most pronounced in patients with low BMI at entry into the studies. CONCLUSIONS: mBMI is well suited to monitor disease progression in TTR-FAP patients. The delay in neurological deterioration brought about by tafamidis treatment in clinical trials is associated with improvements in, or maintenance of, mBMI. FUNDING: This study was sponsored by Pfizer Inc., New York, USA. Options: A: Tafamidis, diflunisal, patisiran, and inotersen may reduce the progression of peripheral neuropathy and improve quality of life, but they may also have varying impacts on mortality and adverse events. B: All pharmacological agents for TTR-FAP have been proven to significantly improve quality of life and reduce mortality without any adverse events. C: Only tafamidis has shown any potential benefit in reducing the progression of peripheral neuropathy, while other agents have shown no significant effects. D: None of the pharmacological agents for TTR-FAP have shown any benefits in clinical trials, and all have significant adverse events.	A
4,630	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What were the findings regarding the efficacy of simulated presence therapy (SPT) for treating behavioural and psychological symptoms and improving the quality of life in people with dementia? Please answer this question based on the information provided below: Evaluation of Simulated Presence: a personalized approach to enhance well-being in persons with Alzheimer's disease. OBJECTIVE: To evaluate the efficacy of Simulated Presence, a personalized approach to enhance well-being among nursing home residents with Alzheimer's disease and related dementia's (ADRD). DESIGN: Latin-Square, double blinded, 3-factor design with restrictive randomization of three treatments (the study intervention, a placebo audio tape of a person reading the newspaper, and usual care). The three factors were treatment, time, and facility type. SETTING: Nine nursing homes in Eastern Massachusetts and Southern New Hampshire. PARTICIPANTS: Fifty-four subjects with documented ADRD who were aged 50 years or older, medically stable, had resided in their current nursing home for at least 3 months, and who had no planned discharge. All subjects had a history of agitated or withdrawn behaviors. INTERVENTION: The purpose of Simulated Presence is to provide a personalized intervention for persons with moderate to severe cognitive impairment. Through a unique testing process, some of the best loved memories of the ADRD person's lifetime are identified and then those memories are introduced to the patient in the format of a telephone conversation using a continuous play audio tape system. The intervention may be used for extended periods of time because each repetition is viewed as a fresh, live telephone call as a result of the short-term memory deficit of the person with ADRD. MEASUREMENTS: Direct observations of outcomes included using a newly developed scale, the Scale for the Observation of Agitation in Persons with Dementia, an agitation visual analog scale, the Positive Affect Rating Scale (mood and "interest"), a withdrawal visual analog scale, and facial diagrams of mood. Reported measures included daily staff observation logs of responses to interventions offered, and weekly staff surveys using the short-form Cohen-Mansfield Agitation Inventory and the Multidimensional Observation Scale for Elderly Subjects (mood and "interest"). Severity of dementia was assessed by the Mini-Mental State Exam, the Test for Severe Impairment, the Bedford Alzheimer's Nursing Scale, and the ADL Self-Performance Scale. RESULTS: Chi-square analysis of direct observations, using facial diagrams, revealed that Simulated Presence was equivalent to usual care (P = .141) and superior to placebo for producing a happy facial expression (P = .001). A positive effect was also documented in nursing staff observation logs using Analysis of Variance techniques (ANOVA) for subjects during Simulated Presence phases compared with the placebo phases (P < .001) and usual care phases (P < .001). According to ANOVA analyses of "interest" from weekly surveys, Simulated Presence was superior to both usual care (P = .001) and placebo (P = .008). We were unable to find evidence of significant differences (P < .05) among interventions for other direct observations and weekly reports of overall agitation or mood aspects of withdrawal. Subjects accepted the intervention most of the time, except for five subjects who refused it more than 50% of the time. CONCLUSION: This study provided evidence that Simulated Presence can be effective in enhancing well-being and decreasing problem behaviors in the nursing home setting as a substitute for or complement to usual care. Management of verbally disruptive behaviors in nursing home residents. BACKGROUND: Verbally disruptive behaviors (VDB) are verbal or vocal behaviors that are inappropriate to the circumstances in which they are manifested. These behaviors are a source of concern because they disturb persons around the older person and may be an indicator of distress. METHODS: Three interventions were tried and compared to a control no-intervention phase. The interventions were: (1) Presentation of a videotape of a family member talking to the older person, (2) in vivo social interaction, and (3) use of music. RESULTS: Thirty-two nursing home residents suffering from dementia and manifesting VDB were observed before, during, and after the interventions, and the duration of VDB was recorded. The behaviors decreased by 56% during the social interaction, 46% during the videotape, 31% during the music, and 16% during the no-intervention. CONCLUSIONS: The effects of the interventions were clinically and statistically significant, indicating the importance of providing stimulating activities and a richer environment to cognitively impaired nursing home residents. A comparison of two treatments of agitated behavior in nursing home residents with dementia: simulated family presence and preferred music. OBJECTIVE: The objective of this study was to compare the effectiveness of two individualized psychosocial treatments in reducing the frequency of physically and verbally agitated behaviors in nursing home residents whose dementia was complicated by marked behavioral disturbance. METHODS: Thirty nursing home residents with frequent, severe behavioral disturbances were observed by research staff before, during, and after multiple, randomized, single-blind exposures to 15-minute audiotapes of simulated family presence (a conversation prepared by a family member about positive experiences from the past), music preferred by the resident in earlier life, and a placebo condition of a reading from a horticultural text. Selected (usually multiple) physical and verbal behaviors were counted as present or absent at regular intervals. All three treatment conditions were compared with usual care. RESULTS: Simulated presence and preferred music both proved effective in reducing counts of physically agitated behaviors. Simulated presence, but not music, resulted in significantly reduced counts of verbally agitated behaviors. The placebo tape proved more effective than expected. Participants' responses to simulated presence and music varied widely. Behavior counts fell by one-half or more in many cases. Other residents became more agitated. CONCLUSION: Participants' better-than-expected responses to the placebo tape suggest that even the simplest technology can improve the lives of confused, disturbed nursing home residents. Of the two psychosocial treatments, preferred music tapes were easier to make and were clearly helpful in many instances. By contrast, family members often struggled to recall enough happy memories to compile a simulated presence tape. Simulated presence might prove just as effective if relatives speak on topics of their own choosing. Although not all residents were helped by these treatments, adverse effects were mild and shortlived. Options: A: SPT was found to be highly effective in reducing behavioural and psychological symptoms and improving quality of life in people with dementia. B: SPT showed some promise in reducing behavioural and psychological symptoms, but its effects on quality of life were inconclusive. C: The evidence was very low quality, and no conclusions could be drawn about the efficacy of SPT for treating behavioural and psychological symptoms or improving quality of life in people with dementia. D: SPT was found to be ineffective in reducing behavioural and psychological symptoms and had no impact on the quality of life in people with dementia.	C
4,631	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the effectiveness of antibiotic prophylaxis in reducing postoperative wound infections in adults undergoing elective open inguinal and femoral hernia repair? Please answer this question based on the information provided below: Polyglycolic acid, silk, and topical ampicillin. Their use in hernia repair and cholecystectomy. The effect of topical ampicillin sodium and polyglycolic acid and silk sutures on the recurrence of an existing hernia or an incisional hernia and on infection rates in clean abdominal wounds (herniotomies and simple cholecystectomies) was studied in a triple-blind, randomized trial with 398 consecutive patients. One infection, three suture sinuses, and two incisional hernias occurred among 113 patients with cholecystectomies, while the corresponding rates in 285 patients with hernia repairs were 11 infections, no suture sinuses, and three recurrent hernias. No effect of ampicillin could be demonstrated, nor was any difference between polyglycolic acid and silk sutures shown. No interaction between the antibiotic and suture material was found, and no side effects were observed. Wound infection was significantly more frequent in patients with postoperative seromas or hematomas. The role of antibiotic prophylaxis in prevention of wound infection after Lichtenstein open mesh repair of primary inguinal hernia: a multicenter double-blind randomized controlled trial. OBJECTIVE: To determine whether the use of prophylactic antibiotics is effective in the prevention of postoperative wound infection after Lichtenstein open mesh inguinal hernia repair. SUMMARY BACKGROUND DATA: A recent Cochrane meta-analysis (2003) concluded that "antibiotic prophylaxis for elective inguinal hernia repair cannot be firmly recommended or discarded." METHODS: Patients with a primary inguinal hernia scheduled for Lichtenstein repair were randomized to a preoperative single dose of 1.5 g intravenous cephalosporin or a placebo. Patients with recurrent hernias, immunosuppressive diseases, or allergies for the given antibiotic were excluded. Infection was defined using the Centers for Disease Control and Prevention criteria. RESULTS: We included 1040 patients in the study between November 1998 and May 2003. According to the intention-to-treat principle, 1008 patients were analyzed. There were 8 infections (1.6%) in the antibiotic prophylaxis group and 9 (1.8%) in the placebo group (P = 0.82). There was 1 deep infection in the antibiotic prophylaxis group and 2 in the placebo group (P = 0.57). Statistical analysis showed an absolute risk reduction of 0.19% (95% confidence interval, -1.78%-1.40%) and a number needed to treat of 520 for the total number of infections. For deep infection, the absolute risk reduction is 0.20% (95% confidence interval, -0.87%-0.48%) with a number needed to treat of 508. CONCLUSIONS: A low percentage (1.7%) of wound infection after Lichtenstein open mesh inguinal (primary) hernia repair was found, and there was no difference between the antibiotic prophylaxis or placebo group. The results show that, in Lichtenstein inguinal primary hernia repair, antibiotic prophylaxis is not indicated in low-risk patients. The role of antibiotic prophylaxis on wound infection after mesh hernia repair under local anesthesia on an ambulatory basis. Mesh prosthesis, local anesthesia, and ambulatory care have been widely introduced in recent decades in the treatment of inguinal hernia. The use of antibiotic prophylaxis during open inguinal hernia repair has been controversial. No prospective trial has been conducted to assess the role of antibiotic prophylaxis in patients operated on for inguinal hernia under the above-mentioned conditions. A prospective, randomized, double-blinded trial was initiated to assess the efficacy of antibiotic prophylaxis in the prevention of wound infection during open mesh inguinal hernia repair under local anesthesia on an ambulatory basis. Ninety-nine consecutive hernia repairs were randomized to receive 1 g of parenteral Cefazolin preoperatively or a placebo. No wound infections existed in the therapeutic group (0/50). Four infections appeared in the control group (4/49), and the study was suspended for ethical reasons when differences reached values close to statistical significance ( P=0.059). We conclude that a single dose of intravenous Cefazolin decreases the risk of wound infection during open mesh inguinal hernia repair under local anesthesia on an ambulatory basis. Prophylactic antibiotic use in elective inguinal hernioplasty in a trauma center. PURPOSE: In this double-blind prospective randomized trial, our objective was to investigate the effect of antibiotic prophylaxis in patients undergoing elective inguinal hernia surgery with mesh repair in a large-volume tertiary referral trauma center. METHODS: Eligible patients were assigned randomly to either an antibiotic prophylaxis group or a control group. Patients in the prophylaxis group were given 1 g cefazolin by IV bolus injection whereas the placebo control group received an equal volume of sterile saline preoperatively. A Lichtenstein repair was done in all cases. The patients were examined for surgical site infection (SSI) and other postoperative local complications before discharge, and reexamined 3, 5, 7, and 30 days after discharge. RESULTS: Groups were well matched for age, sex, coexisting diseases, ASA scores, type of hernia, type of anesthesia, duration of surgery. Incidence of infection was 7% in the control group (7/100) and 5% in the prophylaxis group (5/100) (P = 0.38). All the infections were superficial and responded well to drainage and proper antibiotic therapy. All other postoperative complications were similar in the two groups. CONCLUSIONS: In our settings antibiotic prophylaxis has no significant effect on the incidence of SSI in elective repair of inguinal hernias with mesh. The most effective way to reduce the incidence of infection in prosthetic repair may be a specific center for treatment of abdominal wall hernias. The reduction of surgical wound infections by prophylactic parenteral cephaloridine. A controlled clinical trial. Role of prophylactic antibiotics in open inguinal hernia repair: a randomised study. To study the role of prophylactic antibiotics in open inguinal hernia repair. A total of 200 patients were included, they were randomised in two groups. Group 1 was given prophylactic dose of inj amoxy-clav while group 2 was given placebo only. Results were compared and Data analysed using the Chi-square test. Complications in both the groups were compared. Rate of serous discharge and seroma formation was 1% and 22% respectively in group 1 while 2% and 26% in group 2 also the rate of erythema and stitch abscess were 1% and none in group 1 and 2% and 1% in group 2 respectively. On statistical analysis these differences were not significant. Addition of prophylactic antibiotics in elective open inguinal hernia repair has no significant benefit over placebo although larger studies are required to prepare some uniform guidelines. The role of antibiotic prophylaxis in mesh repair of primary inguinal hernias using prolene hernia system: a randomized prospective double-blind control trial. Antibiotic prophylaxis is being commonly used in mesh repair of inguinal hernia but its role has been questioned in a recent Cochrane analysis performed in 2003. Routine use of antibiotic prophylaxis in mesh repair of inguinal hernia can lead to bacterial resistance and increase in cost. In a present double-blind placebo controlled trial involving 120 patients undergoing inguinal hernia repair using prolene hernia system, we did not find any benefit of the routine use of antibiotic prophylaxis in terms of wound infection rate. Local antibiotic prophylaxis in inguinal hernia repair. We compared the effects of single dose (750 milligrams) prophylactic cefamandole delivered directly into the operative wound with local anesthesia (n = 162) with a control group (no antibiotics) (n = 162) in a randomized trial. No adverse effects were observed. There were seven wound abscesses in the untreated group compared with none in the group receiving antibiotic prophylaxis (p = 0.007). Six of the seven abscesses occurred as late as one month after the patient was discharged from the hospital. The costs of antibiotics used were ten times less than the costs of treatment of wound complications in the control group. A randomized trial of antibiotic prophylaxis for the prevention of surgical site infection after open mesh-plug hernia repair. BACKGROUND: The efficacy of antibiotic prophylaxis for the prevention of surgical-site infection (SSI) after open tension-free inguinal hernia repair remains controversial. METHODS: A double-blind, randomized, placebo-controlled trial was conducted. Patients who underwent elective open mesh-plug hernia repair were eligible for randomization. In the antibiotic prophylaxis group, 1.0 g cefazolin was intravenously administrated 30 minutes before the incision. In the placebo group, an equal volume of sterile saline was administered. The primary end point was the incidence of SSI. RESULTS: A total of 200 patients were enrolled. SSI developed in 2 of 100 patients (2%) in the antibiotic prophylaxis group and 13 of 100 patients (13%) in the placebo group, indicating a significant difference between the 2 groups (relative risk ratio, 0.25; 95% confidence interval, 0.070 to 0.92; P = .003). Other complications occurred in 23 patients: 7 (7%) in the antibiotic prophylaxis group and 16 (16%) in the placebo group (P = .046). CONCLUSIONS: This study indicates that antibiotic prophylaxis is effective for the prevention of SSI after open mesh-plug hernia repair. Prospective randomized evaluation of prophylactic antibiotic usage in patients undergoing tension free inguinal hernioplasty. OBJECTIVES: Assessment of the usefulness of antibiotic prophylaxis in inguinal hernioplasty. MATERIALS AND METHODS: This prospective randomized double blind study was conducted on 98 patients. Group A (50 patients) received a single dose of intravenous amoxicillin and clavulanic acid, and Group P (48 patients) received an equal volume of normal saline placebo by intravenous bolus 30 min before the induction of anesthesia. Hernioplasty was performed with polypropylene mesh. Skin was closed using skin staples that were removed after complete wound healing. The surgical site infection was diagnosed according to APIC, CDC criteria ( http://www.apic.org ). RESULTS: The mean operative time was 38.8 ± 10.8 min in group A versus 40.9 ± 11.1 min in group P (P = 0.34). The mean hospitalization time was 1.3 ± 0.463 days in group A versus 1.25 ± 0.438 days in group P (P = 0.58). Four patients (2%) in group A and 6 patients (2.88%) in group P had wound infections (P = 0.47). Group A had 3 superficial infections and 1 deep infection while group P had 5 superficial infections and 1 deep infection. Antibiotic treatment of the wound infection was successful in all patients. Wound culture showed Staphylococcus aureus infection in 1 patient each group, Streptococcus pyogenes in 1 group A patient and Pseudomonas aeruginosa in 1 group P patient. Cultures in other patients in both groups were reported to be sterile. CONCLUSION: Prophylactic antibiotic usage in patients undergoing tension free inguinal hernioplasty did not show any statistically significant beneficial effects in reduction of surgical site infection. A randomized, double-blind, placebo-controlled trial to determine effectiveness of antibiotic prophylaxis for tension-free mesh herniorrhaphy. BACKGROUND: In recent years, use of prosthetic material for inguinal hernia repair has increased dramatically. Tension-free repairs have gained popularity not only for recurrent or complicated hernias, but for primary hernia repairs as well. Although routine use of prophylactic antibiotics is not recommended in the Philippines for open nonimplant herniorrhaphy, there is little direct clinical evidence on which to base recommendations when implantable mesh is used. STUDY DESIGN: We conducted a prospective, randomized, double-blind, placebo-controlled trial comparing wound infection rates in 360 patients (180 received prophylactic antibiotics, 180 received a placebo) undergoing primary inguinal hernia repair electively using polypropylene mesh. Age, gender, American Society of Anesthesiologists class, type of hernia, type of anesthesia, and duration of operation were recorded. Infections were evaluated 1 week, 2 weeks, and 1 month after operation by an independent surgeon. All complications were recorded. Results were assessed using chi-square, Fisher's exact test, and Student's t-tests as appropriate. RESULTS: Groups were well matched for all preoperative variables studied, including comorbid conditions. Six patients from the antibiotic group and four from the placebo group failed to followup after the second week. Superficial surgical site infection developed in 3 patients (1.7%) from the antibiotic group and 6 (3.3%) from the placebo group (p = 0.50). One from each group developed deep surgical site infection. Both patients were readmitted and underwent repeated debridement, which eventually resulted in graft loss. CONCLUSIONS: Preoperative administration of single-dose antibiotic for tension-free inguinal mesh herniorrhaphy did not markedly decrease risk of wound infection in this patient population. Our results do not support use of antibiotic prophylaxis for tension-free mesh herniorrhaphy. Perioperative antibiotic prophylaxis for herniorrhaphy and breast surgery. We assessed the efficacy of perioperative antibiotic prophylaxis for surgery in a randomized, double-blind trial of 1218 patients undergoing herniorrhaphy or surgery involving the breast, including excision of a breast mass, mastectomy, reduction mammoplasty, and axillary-node dissection. The prophylactic regimen was a single dose of cefonicid (1 g intravenously) administered approximately half an hour before surgery. The patients were followed up for four to six weeks after surgery. Blinding was maintained until the last patient completed the follow-up and all diagnoses of infection had been made. The patients who received prophylaxis had 48 percent fewer probable or definite infections than those who did not (Mantel-Haenszel risk ratio, 0.52; 95 percent confidence interval, 0.32 to 0.84; P = 0.01). For patients undergoing a procedure involving the breast, infection occurred in 6.6 percent of the cefonicid recipients (20 of 303) and 12.2 percent of the placebo recipients (37 of 303); for those undergoing herniorrhaphy, infection occurred in 2.3 percent of the cefonicid recipients (7 of 301) and 4.2 percent of the placebo recipients (13 of 311). There were comparable reductions in the numbers of definite wound infections (Mantel-Haenszel risk ratio, 0.49), wounds that drained pus (risk ratio, 0.43), Staphylococcus aureus wound isolates (risk ratio, 0.49), and urinary tract infections (risk ratio, 0.40). There were also comparable reductions in the need for postoperative antibiotic therapy, non-routine visits to a physician for problems involving wound healing, incision and drainage procedures, and readmission because of problems with wound healing. We conclude that perioperative antibiotic prophylaxis with cefonicid is useful for herniorrhaphy and certain types of breast surgery. Prophylactic antibiotics in open mesh repair of inguinal hernia - a randomized controlled trial. The role of prophylactic antibiotics in mesh repair of inguinal hernia is unclear. A Cochrane meta-analysis in 2005 concluded that "antibiotic prophylaxis for elective inguinal hernia repair cannot be firmly recommended or discarded" and "further studies are needed, particularly on the use for mesh repair." So, we designed a study to define the role of prophylactic antibiotics in mesh repair of inguinal hernia. We conducted a prospective, randomized, double-blind, trial comparing wound infection rates in 450 patients (225 received intravenous Cefazolin, 225 received a placebo) undergoing primary inguinal hernia repair electively using polypropylene mesh. 334 patients who completed a followup period of one month were analyzed. Age, American Society of Anesthesiologists class, type of hernia, type of anesthesia, grade of surgeon, pre and postoperative hospital stay and duration of operation were recorded. CDC criteria was used to define wound infection. Groups were well matched for all preoperative variables studied. The overall infection rate was 8.7% (29 out of 334). The incidence of wound infection in antibiotic group was 7% and 10.5% in control group. One from each group developed deep surgical site infection. Most of the infections occurred between the 7th and 12th post-operative day after discharge from the hospital. Antibiotic prophylaxis was associated with decreased incidence of wound infection when compared to control group, but the difference was not statistically significant. Based on our results we do not recommend the routine use of antibiotic prophylaxis in elective mesh repair of inguinal hernias. Antibiotic prophylaxis and open groin hernia repair. Antibiotic prophylaxis is not routinely given for nonimplant, clean operations, although this view has recently been challenged. We have conducted a randomized multicenter, double-blind prospective trial to compare co-amoxiclav with placebo in 619 patients undergoing open groin hernia repair. Altogether 563 (91%) patients fulfilled the protocol; 283 received co-amoxiclav and 280 placebo. There was no difference between the groups in the number of patients receiving local or general anesthetic, the type of repair performed, the use of a subcutaneous fat suture, the type of skin closure used, the use of wound analgesia, or the use of a wound drain. Patients were given a card to return to the hospital in the event of their wound discharging or their needing to see their general practitioner. All patients were reviewed at approximately 6 weeks after operation. Fifty (8.9%) patients sustained a wound infection, 25 in the co-amoxiclav group and 25 in the placebo group. We conclude that antibiotic prophylaxis is of no benefit to patients undergoing open groin hernia repair. Prophylactic antibiotic usage in patients undergoing inguinal mesh hernioplasty - A clinical study. BACKGROUND: There is ambiguity about the use of antibiotic prophylaxis in inguinal mesh hernioplasty. We have tried to assess the efficacy of antibiotic prophylaxis in this procedure. MATERIALS AND METHODS: A randomized double blind placebo controlled study was conducted which included 55 patients who underwent an inguinal mesh hernioplasty over a 2 year period. The patients were evaluated for the status of the suture line as well as the presence of wound infection. RESULTS: Out of 55 patients 29 were randomized to the antibiotic arm and 26 to the placebo group. The groups were well matched for all variables studied excluding wound infections, which occurred at a rate of 10.34% (n = 3) in the antibiotic group and 15.38% (n = 4) in the placebo arm, (p > 0.01). CONCLUSION: This study did not document any statistically significant difference observed between those who received antibiotics and those receiving placebo in terms of any of the prognostic end points evaluated for Lichtenstein mesh hernioplasty. The role of antibiotic prophylaxis in elective tension-free mesh inguinal hernia repair: results of a single-centre prospective randomised trial. Hernia repair is one of the so-called clean operations. Many surgeons, however, use antibiotics, especially in the mesh repair era, without strong evidence to support this policy. We conducted a single-centre prospective randomised trial with a view to clarify this issue on a scientific basis. From January 2000 all patients undergoing elective inguinal hernia repair using a tension-free polypropylene mesh technique, provided they fulfilled predetermined criteria, were randomised to have a single dose of amoxicillin and clavoulanic acid or placebo in a double-blind manner. The main end point was to detect any difference in infectious complication rates - with specific interest to wound infection rates - between the two groups. Between January 2000 and June 2004, 386 patients entered the study (364 men and 22 women, median age 63 years, range 15-90 years) and were randomised to have antibiotic prophylaxis (group A, n = 193) or placebo (group B, n = 193). The two groups were comparable regarding demographic data. In total, 19 (5%) cases with infectious complications were detected. Fourteen of these were wound infections (3.7%). There were five cases of wound infection in group A and nine in group B (p = 0.4, Fisher's exact test). All wound infections were treated with antibiotics. The wound was opened in some cases. Mesh removal was not required in any of the cases. From the results of this study it does not appear that antibiotic prophylaxis offers any benefits in the elective mesh inguinal hernia repair. Efficacy of preoperative single dose antibiotic in patients undergoing mesh repair for inguinal hernia. BACKGROUND: Inguinal hernia is the commonest type of external hernias. Lichtenstein mesh repair is the most favoured technique of inguinal hernia repair nowadays. It is tension free repair of weakened inguinal wall using polypropylene mesh. The present study was conducted to determine the efficacy of single dose antibiotic with placebo on patients undergoing inguinal hernia mesh repair. METHODS: This randomised controlled trial was carried out in the Department of General Surgery, Ayub Teaching Hospital, Abbottabad from January to December 2011. The study population included male patients presenting with primary unilateral inguinal hernia, above 18 years of age. Mesh repair was performed in all patients. The patients were randomly divided into two groups. Patients in group A were given a single dose of antibiotic before inguinal hernia mesh repair and patients in group B were given placebo before inguinal hernia mesh repair. Efficacy of antibiotic and placebo was accessed in terms of surgical site infections (SSIs). RESULTS: A total of 166 cases of inguinal hernia mesh repair patients were recorded during the study period. A total of 83 patients were recruited in each group. Surgical site infection was found in 6 (7.2%) in Group B it was 15 (18.1%). The difference being statistically significant (p = 0.036). CONCLUSION: Antibiotic prophylaxis is a preferred option for mesh plasty. Prospective randomized, double-blind, placebo controlled trial to evaluate infection prevention in adult patients after tension-free inguinal hernia repair. OBJECTIVE: Infection is one of possible complications after prosthetic material hernia repair surgery. Antibiotic prophylaxis is applied routinely in China, but its effect is still controversial. The present study aims to offer direct clinical evidence on prevention of infection after tension-free inguinal hernia repair. METHODS: A total of 1,200 cases with primary inguinal hernia treated in 6 hospitals in Shaanxi Province were enrolled in this study. They were randomly divided into three groups (n = 400 per group): placebo control group, Cefazolin group and Levofloxacin group after tensionfree inguinal hernia repair using polypropylene mesh. Hernia type, age, gender, weight and complications were recorded. The surgical-site infection was diagnosed according to APIC, CDC criteria (http://www.apic. org). Infections were evaluated every other day in the first week, and then at 14 days, 21 days and 30 days following surgery. RESULTS: Two cases from the placebo group, 3 from the Cefazolin group and 3 from the Levofloxacin group failed to follow-up. Six patients (2 non-following the protocol, 2 severe depression, and 2 laparoscopic surgery) from the placebo group, 14 (8 nonreceiving trial medication, 5 laparoscopic surgery, and 1 failure to tolerance) from the Cefazolin group, and 12 (2 combination of antibiotic usage, 5 laparoscopic surgery and 5 failure to tolerance) from the Levofloxacin group were excluded. The data of the 1,160 cases were statistically analyzed in the incidence rates of surgical-site infection and complications after inguinal hernia repair. Surgical-site infection including wound infection, cellulitis or mesh-related infection was found in 20 cases (5.1%) of the control group, 15 (3.92%) of the Cefazolin group and 17 (4.42%) of the Levofloxacin group, and the difference among the three groups was not statistically significant (χ2 = 0.438, p = 0.803). There was also no significant difference in post-surgery complications including seroma (p = 0.6366), urinary retention (p = 0.8136), fat liquefaction (p = 0.8061), pulmonary infection (p = 0.1911), and urinary tract infection (p = 0.8144) among the three groups. CONCLUSIONS: Prophylactic use of Cefazolin or Levofloxacin did not significantly decrease the risk of wound infection in these patients undergoing inguinal hernia repair. The present results do not support the administration of antibiotic prophylaxis for tension-free inguinal hernia repair. *The authors contributed equally to this work. Effect of single-dose prophylactic ampicillin and sulbactam on wound infection after tension-free inguinal hernia repair with polypropylene mesh: the randomized, double-blind, prospective trial. OBJECTIVE: To assess the value of single-dose, intravenous, prophylactic ampicillin and sulbactam (AS) in the prevention of wound infections during open prosthetic inguinal hernia repair by a double-blind, prospective, randomized trial. SUMMARY BACKGROUND DATA: The use of antibiotic prophylaxis during open prosthetic inguinal hernia surgery is controversial, and no prospective trial has been conducted to examine this issue. METHODS: Patients undergoing unilateral, primary inguinal hernia repair electively with the Lichtenstein technique using polypropylene mesh were randomized to receive 1.5 g intravenous AS before the incision or an equal volume of placebo according to a predetermined code of which the surgeons were unaware. Patients with recurrent, femoral, bilateral, giant, or incarcerated hernias or any systemic diseases were excluded. Age, sex, body mass index, American Society of Anesthesiologists score, type of hernia, type of anesthesia, duration of surgery, and use of drains were recorded. Infection was defined according to the criteria of Centers for Disease Control. Patients were evaluated 1 week, 1 month, 6 months, and 1 year after surgery by an independent surgeon. All complications were recorded. Results were assessed using chi-square, Fisher's exact, and Student t tests as appropriate. RESULTS: Between September 1996 and July 1998, 280 patients (140 AS, 140 placebo group) entered the protocol. Four patients from the AS group and seven from the placebo group were excluded because of inadvertent antibiotic administration or follow-up problems. Groups were well matched for all the variables studied and postoperative complications, excluding wound infections, which occurred at a rate of 0.7% in the AS group and 9% in the placebo group (P =.00153). Twelve patients in the placebo group developed wound infections, requiring five repeat hospital admissions in three patients. These three patients suffered deep infections reaching the graft, which resulted in graft loss in two. The single infected patient in the AS group had his graft removed as well because of deep persistent infection. CONCLUSIONS: This study documented a significant (10-fold) decrease in overall wound infections when single-dose, intravenous AS was used during Lichtenstein hernia repair. Deep infections and wound infection-related readmissions were also reduced by the use of AS. Proponents of mesh repairs may therefore be advised to use prophylactic single-dose intravenous antibiotic coverage in the light of the results of this trial. AS proved to be an effective antimicrobial agent. Options: A: Antibiotic prophylaxis significantly reduces the risk of all types of postoperative wound infections in both herniorrhaphy and hernioplasty surgeries. B: Antibiotic prophylaxis probably makes little or no difference in preventing wound infections after hernioplasty surgery in a low infection risk environment, but may reduce the risk of all wound infections and SSSI in a high-risk environment. C: Antibiotic prophylaxis is highly effective in preventing deep surgical site infections (DSSI) in both low and high infection risk environments. D: Antibiotic prophylaxis is not effective in reducing any type of postoperative wound infections in hernia repair surgeries.	B
4,632	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What was the main finding regarding the comparison between transverse and vertical groin incision techniques for accessing the femoral artery in terms of surgical wound infection? Please answer this question based on the information provided below: Vascular reconstruction at the groin: oblique or vertical incisions? Incisions for vascular access at the groin are usually vertical. Because such incisions cross the moist skin-crease area and disrupt lymphatics, they may be more prone to infection than oblique incisions placed above and parallel to the groin crease. To determine whether this was the case, 149 patients undergoing vascular reconstruction through a groin incision over a period of 30 months were studied. Those with previous groin incisions were excluded, and where an incision was necessary in both groins, each wound was studied separately. Over a 10-day postoperative period 5 of 85 vertical wounds developed infection with purulent discharge, whereas no oblique wounds (n = 82) became infected (P = 0.032). Oblique incisions for vascular access at the groin are associated with a decreased incidence of wound infection compared with conventional vertical incisions. Vertical or transverse incisions for access to the femoral artery: a randomized control study. BACKGROUND: To look at wound complications with either a transverse or vertical groin incision in vascular surgery. METHODS: All patients undergoing vascular procedure requiring access to femoral vessels were randomized to either a vertical or transverse incision. Patients were followed up for 28 days after the procedure and examined for wound infection, wound breakdown, development of lymphatic leak and lymphatic collection. RESULTS: 88 patients (116 groins) were randomised to either incision. Of these, 55 groins had transverse incisions and the remaining had vertical incisions. There was no significant difference in the patient's age, sex, smoking, diabetes, operative times and use of prosthetic material. 29/61 (47.5%) of vertical incisions and 7/55 (12.7%) of transverse incisions had wound complications (p<0.001). There were 13(11%) wound infections in the 116 groins by day 28. There were 3 wound infections in the transverse group and 10 infections in the vertical group (p=0.062). There were 17 (27.9%) lymphatic leaks in the vertical incisions compared to 7(12.7%) in the transverse incisions (p=0.044). The majority of infections were diagnosed after patient discharge from hospital. CONCLUSION: Wound complications are higher with vertical incision. Many infections are diagnosed after patient discharge. We recommend transverse incisions for access to the femoral vessels in the groin. Options: A: Transverse groin incision resulted in a higher risk of surgical wound infection compared to vertical groin incision. B: Transverse groin incision resulted in a lower risk of surgical wound infection compared to vertical groin incision. C: There was no difference in the risk of surgical wound infection between transverse and vertical groin incisions. D: The risk of surgical wound infection was not evaluated in the comparison between transverse and vertical groin incisions.	B
4,633	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the effect of indocyanine green fluorescence angiography (ICGA) on postoperative complications in women undergoing immediate breast reconstruction following skin-sparing mastectomy? Please answer this question based on the information provided below: ICG angiography in immediate and delayed autologous breast reconstructions: peroperative evaluation and postoperative outcomes. Postoperative complications in patients undergoing autologous breast reconstruction should be kept at the lowest possible level. Optimization of autologous breast reconstruction, especially techniques that can identify tissue perfusion and ischemia, will greatly benefit the patients and consequently society. Hence, the aim of this study was to evaluate the complication rates for autologous pedicle flap breast reconstructions, with and without the use of ICG-angiography. A single-institution retrospective review of mastectomy patients was performed. A total of 230 cases who underwent immediate or delayed, unilateral or bilateral pedicle autologous flap breast reconstruction between January 2013 and September 2016 was reviewed. Complication rates in the ICG-angiography and clinical assessment group were evaluated and compared. A total of 191 cases were identified of which 77 were evaluated with ICG-angiography, and 114 were evaluated clinically. There was no significant difference in overall complication rates between the two groups (ICG-angiography, 36.4%; Clinical assessment, 37.7%; p = .88). No significant difference was observed when stratifying for major or minor complications. However, when stratifying for the timing of the reconstruction, the rate of major complications was significantly lower in the ICG-angiography group (ICG-angiography, 0%; Clinical assessment 23.3%; p = .039). BMI was significantly associated with increased risk of minor complications (p = .018), whereas there was no correlation to age, prior smoking, chemotherapy, radiation, diabetes, or hypertension. Our study found that use of ICG-angiography was associated with a significant decrease in the rate of major complications for immediate autologous reconstructions. Postmastectomy Reconstruction Outcomes After Intraoperative Evaluation with Indocyanine Green Angiography Versus Clinical Assessment. BACKGROUND: Mastectomy flap necrosis is a major complication in patients undergoing tissue expander-based reconstruction. This study compared the complication rates following mastectomy and immediate reconstruction with intraoperative indocyanine green (ICG) angiography evaluation to those with clinical assessment only. METHODS: We performed a single-institution retrospective study of mastectomy patients who underwent immediate tissue expander-based reconstruction between September 2009 and December 2013. ICG angiography was adopted in March 2012. The rates of complications in the ICG and clinical assessment only groups were compared. Factors associated with complications were identified with the Fischer exact test and univariate analysis. RESULTS: A total of 114 patients were identified; clinical assessment only, 53 patients; ICG angiography, 61 patients. The overall complication rates were not significantly different between the two groups (ICG angiography, 50.8 %; clinical assessment, 43.4 %; p = 0.46). There was no significant difference in the rates of unexpected return to the operating room, cellulitis, hematomas, and seromas. The overall rates of flap necrosis were not significantly different (ICG angiography, 27.9 %; clinical assessment, 18.9 %; p = 0.28). However, the rates of severe flap necrosis were significantly lower with intraoperative ICG angiography (4.9 %) than with clinical assessment only (18.9 %, p = 0.02). On univariate analysis, breast weight (≥500 g) was significantly associated with increased rates of severe flap necrosis (p = 0.04), whereas body mass index, age, smoking status, prior breast surgery, history of radiation therapy, and receipt of nipple-sparing mastectomy were not. CONCLUSIONS: We observed that the implementation of intraoperative ICG angiography was associated with a significant decrease in the rate of severe flap necrosis. An outcome analysis of intraoperative angiography for postmastectomy breast reconstruction. BACKGROUND: Intraoperative angiography is a useful tool for predicting both tissue perfusion during postmastectomy breast reconstruction and mastectomy flap and free flap survival. OBJECTIVES: The authors determine whether the routine use of laser-assisted indocyanine green (ICG) fluorescence angiography (SPY Imaging; LifeCell Corp, Branchburg, New Jersey) in breast reconstruction decreases the incidence of complications and whether this new technology is cost-effective. METHODS: A retrospective review was conducted for 184 consecutive patients who underwent breast reconstruction using intraoperative ICG angiography from April 2009 to December 2011 at Emory University (Atlanta, Georgia). The incidence of complications (including mastectomy skin necrosis, flap necrosis, fat necrosis, unexpected reoperations, infections, and dehiscence) among these patients was compared with data for 184 consecutive patients who underwent breast reconstruction at Emory University from October 2007 to April 2009, prior to the introduction of ICG angiography. Patient data recorded included age, body mass index, smoking status, and history of preoperative radiation as well as the timing and type of reconstruction, along with complications. The cost of unexpected reoperations for perfusion-related complications and associated hospital stays was calculated. RESULTS: The 184 patients who underwent procedures using ICG angiography imaging had a lower incidence of mastectomy skin necrosis (13% vs 23.4%; P = .010) and unexpected reoperations for perfusion-related complications (5.9% vs 14.1%, P = .009). The 184 patients who underwent procedures without ICG angiography had a higher mean degree of severity of mastectomy skin necrosis (2.22 vs 1.83 on a scale of 1-3; P = .065). There were no significant differences in the degree of flap necrosis, nipple necrosis, fat necrosis, dehiscence, infection, implant exposure, flap loss, seroma, hematoma, or the number of overall complications between the 2 groups. The use of ICG angiography saved patients an average of $610. CONCLUSIONS: The use of ICG angiography during postmastectomy breast reconstruction decreased the incidence and severity of mastectomy skin necrosis as well as the incidence of unexpected reoperations for perfusion-related complications. The technology was found to be cost-effective. Prediction of Skin Necrosis after Mastectomy for Breast Cancer Using Indocyanine Green Angiography Imaging. BACKGROUND: In immediate tissue expander reconstruction following total mastectomy for breast cancer, indocyanine green angiography (ICGA)-guided skin trimming is useful for the prevention of complications. However, instances of unclear ICGA contrast can occur with this method, which are difficult to judge as to whether preventive trimming is warranted. To further improve the mastectomy flap necrosis rate, more accurate objective parameters are necessary. METHODS: The degree of clinical improvement was compared between 81 patients trimmed according to the surgeon's judgment (non-ICGA group) and 100 patients with ICGA-guided trimming (ICGA group). We then retrospectively measured 3 parameters [relative perfusion (RP); time (T) to reach RPmax; and slope (S = RP/T) reflecting the rate of increase to RPmax] by using region of interest analysis software and examined their relationships with skin necrosis. RESULTS: The rate of grade III necrosis (reaching the subcutaneous fat layer) was significantly lower in the ICGA group (4.8%) than in the non-ICGA group (17.8%; CONCLUSIONS: ICGA-guided trimming decreased the rate of deep skin necrosis requiring additional surgical treatment. Region of interest analysis indicated that a relatively low percentage luminescence (RP < 34) was indicative of the need for skin trimming, combined with a slow increase in the perfusion of the mastectomy skin flaps. Laser-assisted indocyanine green angiography in implant-based immediate breast reconstruction: a retrospective study. OBJECTIVE: Necrosis in implant-based immediate breast reconstruction is a feared complication. Accurate evaluation of mastectomy skin flaps per-operatively is necessary to decrease this risk. The present study is the first in Scandinavia to review the effects of perioperative evaluation with laser-assisted indocyanine green fluorescence angiography (LA-ICGA). METHOD: A retrospective review was performed using data from the electronic patient record at the Department of Plastic and Breast Surgery at Aarhus University Hospital in Denmark on all patients who underwent implant-based skin-sparing immediate breast reconstruction with ADM in the time period March 2012 to October 2015. A total of 92 patients undergoing 128 breasts reconstructions were included in the study. An evaluation of complications before and after the implementation of LA-ICGA was performed. RESULTS: No significant difference in necrosis rates requiring surgical revision (p = .411) or conservative treatment (p = .149) in patients undergoing implant-based immediate breast reconstruction were found. CONCLUSION: Our results differ from previously published studies in that no beneficial effect on necrosis rates of was found after implementing LA-ICGA, possibly due to our limited sample size. Tailoring through Technology: A Retrospective Review of a Single Surgeon's Experience with Implant-Based Breast Reconstruction before and after Implementation of Laser-Assisted Indocyanine Green Angiography. Reported complication rates of implant-based breast reconstruction in the literature exceed 50%, with mastectomy skin flap necrosis reported to occur in up to 25% of cases. Laser-assisted indocyanine green angiography (LA-ICGA) technology allows the surgeon to optimize preservation of the mastectomy skin flap while avoiding skin necrosis. The purpose of this study was to determine if outcomes of breast reconstruction are beneficially affected by using LA-ICGA. A total 269 consecutive women (467 breast reconstructions) undergoing implant-based breast reconstruction from 2008 to 2013 were examined. The complication rates of those who underwent reconstruction prior to the implementation of LA-ICGA were compared with those who were reconstructed after implementation of LA-ICGA. A total of 254 consecutive breast reconstructions were performed prior to implementation of LA-ICGA, and 213 breasts were reconstructed with the use of LA-ICGA. After implementation of LA-ICGA System, the rate of mastectomy skin flap necrosis decreased by 86% (6.7% versus 0.9%, p = 0.02). The overall complication rate prior to LA-ICGA was 13.8% compared with 6.6% with the use of LA-ICGA (p = 0.01). After LA-ICGA was incorporated, the percentage of patients undergoing single-stage reconstruction increased from 12% to 32% (p = <0.001). Implementation of LA-ICGA provides the surgeon with an objective assessment of mastectomy flap perfusion resulting in a trend toward overall reduction in complications as well as an 86% decrease in the rate of subsequent skin necrosis. The objective assessment of mastectomy flap perfusion allows the surgeon to tailor breast reconstruction intraoperatively, in real-time, adjusting for the individual patient's mastectomy flap perfusion. A Prospective Study of Immediate Breast Reconstruction with Laser-Assisted Indocyanine Green Angiography. BACKGROUND: Complication rates following immediate breast reconstruction range from 4% to 60%. Mastectomy skin flap necrosis (MSFN) is often the sentinel event leading to secondary complications. METHODS: All patients undergoing immediate reconstruction were enrolled. Upon mastectomy completion, the surgeon visually interpreted the skin flaps, performed laser-assisted indocyanine green angiography (LAIGA), and intervened if needed. Patients were followed for 90 days, documenting skin necrosis, infection, seroma, hematoma, implant loss, and reoperation. RESULTS: There were 126 patients who had 206 immediate breast reconstructions. The complication rate was 22.3%. The incidence of MSFN was 14.1%. The reoperation rate was 8.7%. There was 1 necrosis-related implant loss. Postoperative surveys were completed on 193 breasts: 137 had visual and LAIGA interpretation of well or adequately perfused, resulting in 5.8% rate of necrosis, 2 reoperations, and no implant losses. Twenty breasts had visual and LAIGA interpretation of marginal or poor perfusion. Sixteen of these underwent intervention. The necrosis rate in this group was 35% with no implant losses. A third group with 26 breasts had adequate visual interpretation with marginal or poor perfusion on LAIGA. Ten breasts had no intervention, and 16 received intervention. The overall necrosis rate in this group was 42.3%, with 4 reoperations for necrosis and 1 implant loss. CONCLUSIONS: LAIGA can more accurately predict complications from MSFN than surgeon assessment alone. When surgeon decision making is supplemented with LAIGA, it reduces the incidence of MSFN, infection, implant loss, and overall unexpected reoperation rate. LAIGA is a valuable adjunct for intraoperative decision making. A Comparison of Methods to Assess Mastectomy Flap Viability in Skin-Sparing Mastectomy and Immediate Reconstruction: A Prospective Cohort Study. BACKGROUND: Skin-sparing mastectomy with immediate reconstruction can yield excellent aesthetic results, but high rates of mastectomy flap necrosis have been reported. A prospective cohort study was undertaken to compare three methods of assessing mastectomy flap viability following skin-sparing mastectomy and immediate reconstruction to determine which is most effective in reducing mastectomy flap necrosis. METHODS: The study group included 60 consecutive patients (99 breasts) undergoing skin-sparing mastectomy and immediate reconstruction with either tissue expanders (n = 39) or transverse rectus abdominis musculocutaneous flaps (n = 21). Mastectomy flap viability was assessed either visually (n = 20), with fluorescein dye and Wood's lamp imaging (n = 20), or by indocyanine green angiography (n = 20). Variation across groups was analyzed using analysis of variance for continuous variables and chi-square test for dichotomous variables. RESULTS: The mean follow-up was 10 months. There were no significant differences in mean age, body mass index, medical history, smoking history, pathologic diagnosis, chemotherapy, or reconstruction type. Mastectomy flap necrosis was observed in eight of 30 breasts in the direct visualization group (27 percent), compared with 14 percent in the indocyanine green angiography group and 3 percent in the fluorescein group (p = 0.03). The reoperation rate in the direct visualization group was 20 percent, compared with 15 percent in the indocyanine green angiography group and 0 percent in the fluorescein group. CONCLUSIONS: Fluorescein dye was associated with the lowest rate of complications after skin-sparing mastectomy, but indocyanine green angiography was also shown to reduce mastectomy flap necrosis compared with direct visualization. Routine imaging of mastectomy flap perfusion seems to be beneficial in skin-sparing mastectomy, but intravenous fluorescein may be as effective as more expensive modalities. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II. Potential of the SPY intraoperative perfusion assessment system to reduce ischemic complications in immediate postmastectomy breast reconstruction. BACKGROUND: The quality and viability of mastectomy flaps remain a central challenge in reconstructive surgery, particularly for immediate breast reconstruction. Insufficient perfusion in tissue flaps is a leading cause of early complications following reconstructive procedures, and clinical judgment alone is not completely reliable for the assessment of flap viability. Accurate and reliable intraoperative methods for assessment of tissue perfusion are needed to help surgeons identify tissue at risk for ischemia and necrosis, thereby allowing for maneuvers to improve tissue flap viability. METHODS: This study evaluates the use of intraoperative laser angiography using the SPY System (LifeCell Corp., Branchburg, NJ) for the assessment of perfusion in mastectomy flaps for immediate breast reconstruction. The SPY System uses the contrast agent indocyanine green, which has an excellent safety profile and pharmacokinetics that allow for repeat evaluations during the same surgical procedure. In recent work, the SPY System has demonstrated high sensitivity and specificity for detection of tissues at risk for ischemia and necrosis during reconstructive surgery. Using a retrospective, chart-review design, the authors compared consecutive cases of immediate breast reconstruction using a prosthesis, before and after implementation of the SPY System. RESULTS: Ninety-one subjects were included in the analysis: 52 prior to SPY (Pre-SPY) and 39 after implementation of SPY (Post-SPY). Baseline characteristics were similar between the groups. Both groups had high rates of comorbidities, chemotherapy, and radiation therapy. The rate of postoperative complications was two-fold higher in the Pre-SPY group compared to the Post-SPY group (36.5% vs. 17.9%); this difference was of borderline significance (P = 0.0631). However, mean number of repeat visits to the OR per patient was significantly higher in the Pre-SPY group (1.21 ± 1.47 vs. 0.41 ± 0.71; P = 0.0023). Of the seven patients with complications in the Post-SPY group, five were identified by SPY as having poor flap perfusion; none were identified by clinical judgment alone. CONCLUSIONS: This study suggests that the SPY System can contribute to reduced ischemia-related complications in a population of women undergoing immediate breast reconstruction following mastectomy for breast cancer. Options: A: ICGA significantly reduces the rates of mastectomy skin flap necrosis (MSFN), reoperation, and infection compared to clinical evaluation alone. B: ICGA significantly increases the rates of mastectomy skin flap necrosis (MSFN), reoperation, and infection compared to clinical evaluation alone. C: ICGA has no significant effect on the rates of mastectomy skin flap necrosis (MSFN), reoperation, and infection compared to clinical evaluation alone. D: The evidence is very low quality and inconclusive, making it uncertain whether ICGA affects the rates of mastectomy skin flap necrosis (MSFN), reoperation, and infection compared to clinical evaluation alone.	D
4,634	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the effect of vaginal preparation with antiseptic solution immediately before cesarean delivery on maternal infectious morbidities? Please answer this question based on the information provided below: Chlorhexidine vaginal wipes prior to elective cesarean section: does it reduce infectious morbidity? A randomized trial. OBJECTIVE: To evaluate the efficacy of preoperative vaginal cleansing using chlorhexidine 0.25% antiseptic wipes on rates of postcesarean section (CS) infectious morbidities (endometritis, febrile morbidity and wound infection). METHODS: This prospective randomized trial was conducted among 218 pregnant women scheduled for term elective CS. Patients were equally divided into two groups by simple randomization. After spinal anesthesia and catheterization under aseptic technique, the study group had preoperative vaginal cleansing using chlorhexidine 0.25% antiseptic wipes for about 1 min, while the control group did not. All cases received the prophylactic antibiotics and the usual abdominal scrub. All participants received the routine postoperative care without other interventions. Adverse postcesarean infectious morbidities such as endometritis, febrile morbidity and wound infection were observed at the time of hospital discharge and weekly for 6 weeks postpartum. RESULTS: Both groups were matched regarding the baseline patients' characteristics (age, gestational age, BMI, operative time and postoperative hospital stay). Overall, post-CS infectious morbidity were significantly reduced from 24.4% in the control group to 8.8% in the intervention group; p value <0.05. Marked reduction was seen in the incidence of endometritis (13.2% in the control group versus 2.9% in the intervention group; p value <0.05). However, fever and wound infection showed no significant difference between both groups. CONCLUSION: Cleansing the birth canal with chlorhexidine 0.25% wipes prior to elective CS appears to be effective in reducing rates of post-CS infectious morbidity mainly endometritis. Vaginal cleansing prior to caesarian section: To do or not to do?: A randomized trial. PURPOSE: To evaluate the efficacy of preoperative vaginal cleansing using povidone-iodine solution 10% on rates of post cesarean section (CS) infectious morbidities (endometritis, febrile morbidity and wound infection). METHODS: This prospective randomized trial was conducted among 226 pregnant women scheduled for term elective CS. Patients were equally divided into two groups by simple randomization method. The study group had preoperative vaginal cleansing using povidone-iodine solution 10% for about 1 min, while the control group did not. All cases received the prophylactic antibiotics and the usual abdominal scrub. Adverse post CS infectious morbidities such as endometritis, febrile morbidity and wound infection were observed at the time of hospital discharge and weekly for 6 weeks postpartum. RESULTS: Both groups were matched regarding the baseline patients' characteristics. Overall, post-CS infectious morbidity was significantly reduced from 20.7% in the control group to 7.5% in the intervention group. Marked significant reduction was seen in the incidence of endometritis (11.8% in the control group versus 2.8% in the intervention group). However, maternal fever and wound infection showed no significant difference between both groups. CONCLUSION: Vaginal cleansing with povidone-iodine solution 10% prior to elective CS appears to be effective in reducing rates of post-CS infectious morbidity mainly endometritis. Preoperative vaginal preparation with povidone-iodine on post-caesarean infectious morbidity. The commonest complication associated with caesarean section is infection. The aim of this study is to investigate the effect of vaginal preparation with povidone-iodine on post-caesarean infection. In this clinical trial, 568 patients were selected for two groups: a treatment group and a control group, each with 284 patients. A vaginal scrub was performed before the routine abdominal scrub, with two 4 × 4 cm sponge sticks saturated with povidone-iodine solution, rotated in the vagina for about 30 s. In the control group, only the abdominal scrub was performed. Patients received a single dose of prophylactic antibiotics, and were reviewed for 6 weeks to look for predefined variables. Post-caesarean endometritis occurred less frequently in the treatment group than in the control group (2.5% vs 1.4%). There was no significant difference for febrile morbidity and wound infection in the two groups. The adjusted odds ratio for endometritis after vaginal preparation was 0.03 (95% CI: 0.008-0.7). Vaginal preparation with povidone-iodine may decrease the risk of post-caesarean endometritis. Effect of vaginal cleansing on postoperative factors in elective caesarean sections: a prospective, randomised controlled trial. OBJECTIVE: To assess the effect of povidone iodine versus benzalkonium chloride, which were applied preoperatively for vaginal disinfection in caesarean sections, on postoperative factors. METHODS: One hundred and twenty patients underwent elective caesarean section were divided into three groups using the simple randomisation method: Group 1 (povidone iodine, n: 41); Group 2 (benzalkonium chloride, n: 39); Group 3 (control group, n: 40). Demographic data, duration of operation, amount of bleeding, postoperative pain, time to first flatulence and defaecation, haematological parameters on postoperative day 1 were compared between three groups. Pain evaluation was performed at 6th and 24th postoperative hour using Visual Analogue Scale. RESULTS: No statistically significant differences were detected between the groups in demographic characteristics. There were no significant differences between the groups with respect to the duration of operation and hospital stay. The patients in the group who underwent povidone iodine vaginal cleansing had statistically significantly less postoperative pain as compared to control group. No difference was observed between the groups in haematological parameters other than C-reactive protein (CRP); however, CRP levels at 24th post-operative hour were significantly lower in Group 1 compared to the other groups. CONCLUSIONS: The preoperative vaginal cleansing with povidone iodine could reduce the postoperative pain, analgesic need and infection parameter. Vaginal cleansing before cesarean delivery to reduce postoperative infectious morbidity: a randomized, controlled trial. OBJECTIVE: The objective of the study was to determine whether vaginal preparation with povidone iodine before cesarean delivery decreased the risk of postoperative maternal morbidities. STUDY DESIGN: The design of the study was a randomized, controlled trial in women undergoing cesarean delivery with subjects assigned to have a preoperative vaginal cleansing with povidone iodine or to a standard care group (no vaginal wash). The primary outcome was a composite of postoperative fever, endometritis, sepsis, readmission, wound infection, or complication. RESULTS: There were 155 vaginal cleansing subjects and 145 control subjects. Overall, 9.0% developed the composite outcome, with fewer women in the cleansing group (6.5%) compared with the control group (11.7%), although the difference was not statistically significant (relative risk, 0.55; 95% confidence interval, 0.26-1.11; P = .11). Length of surgery, being in labor, and having a dilated cervix were all associated with the composite morbidity outcome. CONCLUSION: Vaginal cleansing with povidone iodine before cesarean delivery may decrease postoperative morbidities, although the reduction is not statistically significant. Chlorhexidine vaginal preparation versus standard treatment at caesarean section to reduce endometritis and prevent sepsis-a feasibility study protocol (the PREPS trial). BACKGROUND: Worldwide caesarean section (CS) delivery is the most common major operation. Approximately 25% of pregnant women undergo a CS in the UK for delivery of their babies. Sepsis and post-natal infection constitute significant maternal mortality and morbidity. Infection following a CS has a number of primary sources including endometritis occurring in 7-17% of women. Sepsis reduction and reduction in antibiotic use have been identified as a national and international priority. The overarching aim of this research is to reduce infectious morbidity from caesarean sections. METHODS: This is a parallel group feasibility randomised controlled trial comparing vaginal cleansing using chlorhexidine gluconate versus no cleansing (standard practice) at CS to reduce infection. Women will be recruited from four National Health Service maternity units. Two hundred fifty women (125 in each arm) undergoing elective or emergency CS, who are aged 16 years and above, and at least 34 weeks pregnant will be randomised. Allocation to treatment will be on a 1:1 ratio. The study includes a qualitative aspect to develop women centred outcomes of wellbeing after delivery. DISCUSSION: The success of the feasibility study will be assessed by criteria related to the feasibility measurements to ascertain if a larger study is feasible in its current format, needs modification or is unfeasible, and includes recruitment, adherence, follow-up and withdrawal measures. TRIAL REGISTRATION: The PREPS trial has been registered with ISRCTN (ISRCTN 33435996). Effect of preoperative vaginal cleansing with an antiseptic solution to reduce post caesarean infectious morbidity. OBJECTIVE: To determine the effectiveness of pre operative vaginal cleansing with an antiseptic solution to reduce post caesarean infectious morbidity. METHODS: An observational case control study was conducted at Department of Obstetrics and Gynaecology, Unit-III, Liaquat University Hospital, Hyderabad from February to July 2010. The 100 women in control group received the standard abdominal preparation only, while the 100 subjects in interventional group also received preoperative vaginal cleansing with 10% pyodine along with the usual abdominal scrub. All subjects received prophylactic antibiotic cover during the surgery. Maternal demographics, surgical parameters and infectious outcome were collected and data compiled on a pre-designed proforma and analysis was done using SPSS 15. RESULTS: The comparison between two groups did not show a significant difference in patient's demographics, labour and surgical variables. Post caesarean endometritis occurred in 1% of case group and 7% of controls (p value: <0.03). There was no measurable effect seen on development of fever and wound infection However, statistically significant reduction in overall composite morbidity i.e. p value: <0.02 and odds ratio 0.335 (CI=0.125-0.896) was seen in patients with vaginal cleansing group when compared with controls. CONCLUSION: Preoperative vaginal cleansing with pyodine has reduced post caesarean infectious morbidities. Vaginal preparation with povidone iodine and postcesarean infectious morbidity: a randomized controlled trial. OBJECTIVE: To determine whether vaginal preparation with povidone iodine before cesarean decreased the incidence of postpartum infectious morbidity. METHODS: Participants were randomly assigned to vaginal preparation with povidone iodine (n = 247) or no preparation (n = 251). Postpartum infectious morbidity included fever, defined as temperature of 38C or greater after the day of surgery; endometritis, defined as fever with abdominal or uterine tenderness and initiation of intravenous antibiotics; and wound separation, defined as disruption of the abdominal incision that required wound care. We calculated overall rates of postpartum infectious morbidity, relative risks (RR), and 95% confidence intervals (CI) for the effect of vaginal preparation. As designed and reported, the trial had at least 80% power to detect a 10% or greater absolute difference in rates of overall infectious morbidity, fever, and endometritis (two-tailed, alpha = 0.05). RESULTS: There was no difference between groups in maternal age, parity, race, education, prior cesarean, type of anesthesia, labor before current cesarean, number of vaginal examinations during labor, internal monitoring, prophylactic antibiotic use, gestational age at delivery, or payment status. Excluding 68 women with chorioamnionitis, incidence of postoperative fever was 19.3%, endometritis 7.2%, and wound separation 7.0%. Vaginal preparation with povidone iodine before cesarean had no effect on risk for fever (RR 1.1, 95% CI 0.8, 1.6), endometritis (RR 1.6, 95% CI 0.8, 3.1), or wound separation (RR 0.6, 95% CI 0.3, 1.3). CONCLUSION: Vaginal preparation with povidone iodine before cesarean had no effect on the incidence of fever, endometritis, or wound infection. Chlorhexidine vaginal irrigation for the prevention of peripartal infection: a placebo-controlled randomized clinical trial. OBJECTIVE: Our purpose was to determine whether chlorhexidine vaginal irrigation prevents maternal peripartal infection. STUDY DESIGN: A double-blinded, placebo-controlled, randomized trial was performed. Single 200 ml irrigations of either 0.2% chlorhexidine solution or sterile water placebo were given in active labor or before planned cesarean delivery. The primary outcome measure was the combined rate of chorioamnionitis and endometritis (which were mutually exclusive diagnoses). RESULTS: A total of 1024 patients were enrolled: 508 in the chlorhexidine group and 516 in the placebo group. The two groups were generally well balanced on important clinical factors but differed (p < 0.05) in rates of nulliparity (chlorhexidine 42%, placebo 52%), intrauterine pressure catheter usage (chlorhexidine 65%, placebo 72%), and presence of meconium (chlorhexidine 17%, placebo 22%). There were no recognized adverse maternal or neonatal reactions to irrigation. Rates of infection (chorioamnionitis + endometritis) did not differ significantly between the groups, chlorhexidine 10% versus placebo 13% (relative risk 0.8, 95% confidence interval 0.5 to 1.1). Stratified and logistic regression analyses supported the primary univariate analysis. Neonatal outcomes, including sepsis rates of 0.4%, were equivalent for the groups. CONCLUSION: As used in this trial, chlorhexidine lacked efficacy in the prevention of maternal peripartal infection. Preoperative vaginal preparation with povidone-iodine and the risk of postcesarean endometritis. OBJECTIVE: Postcesarean endometritis and wound infection remain significant morbidities, despite use of strategies to prevent these complications. We investigated the effect of preoperative vaginal preparation with povidone-iodine as a preventive intervention against postcesarean endometritis and wound infection. METHODS: A randomized controlled study was performed in 308 women undergoing nonemergent cesarean delivery. Subjects received either standard abdominal scrub alone or abdominal scrub with an additional vaginal preparation with povidone-iodine solution. All subjects received prophylactic antibiotic at the time of umbilical cord clamping. Each subject's postoperative course was reviewed for development of febrile morbidity (temperature > 38.0 degrees C), endometritis (temperature > 38.4 degrees C accompanied by fundal tenderness occurring beyond the first postoperative day, in the absence of evidence of other infection), and wound infection. RESULTS: Postcesarean endometritis occurred in 7.0% of subjects who received a preoperative vaginal preparation and 14.5% of controls (P < .05). There was no measurable effect of a vaginal scrub on the development of postoperative fever or wound infection. The adjusted odds ratio for developing endometritis after a vaginal preparation was 0.44 (95% confidence interval [CI] 0.193-0.997). Multivariate analysis showed an increased risk of developing endometritis in association with severe anemia (adjusted OR 4.26, 95% CI 1.568-11.582), use of intrapartum internal monitors (adjusted OR 2.84, 95% CI 1.311-6.136), or history of antenatal genitourinary infection (adjusted OR 2.9, 95% CI 1.265-6.596). CONCLUSION: Preoperative vaginal scrub with povidone-iodine decreases the incidence of postcesarean endometritis. This intervention does not seem to decrease the overall risk of postoperative fever or wound infection. Does vaginal preparation with povidone-iodine prior to caesarean delivery reduce the risk of endometritis? A randomized controlled trial. OBJECTIVE: The purpose of the present study was to determine whether the vaginal preparation with povidone-iodine prior to caesarean delivery decreased the incidence of postpartum endometritis. METHODS: The present study was a prospective randomized controlled trial in which subjects received a vaginal preparation with povidone-iodine solution immediately prior to caesarean delivery or received no vaginal preparation. The primary outcome measure was the rate of postpartum endometritis. RESULTS: A significant decrease in post-caesarean endometritis was noted in the group that received the povidone-iodine vaginal preparation (n = 334) compared with the control group (n = 336) [6.9 vs. 11.6%; RR = 1.69; 95% CI = 1.03-2.76]. No statistically significant differences in the incidence of endometritis were noted between the experimental and control groups among women who were not in labor at the time of the caesarean delivery [9.2 vs. 8.6%; RR = 1.05; 95% CI = 0.58-1.90], and no differences were found between groups when women with ruptured membranes were excluded from the analysis [9.6 vs. 6.7%; RR = 1.39; 95% CI = 0.78-2.47]. CONCLUSIONS: Vaginal preparation with povidone-iodine solution immediately prior to a caesarean delivery reduces the risk of post-operative endometritis. This preemptive measure was only found to be beneficial in women whose membranes had ruptured and those who were in labor prior to caesarean surgery. Options: A: It increases the risk of post-cesarean endometritis, postoperative fever, and postoperative wound infection. B: It has no significant effect on the risk of post-cesarean endometritis, postoperative fever, and postoperative wound infection. C: It probably reduces the risk of post-cesarean endometritis, postoperative fever, and postoperative wound infection. D: It causes significant adverse effects and should be avoided.	C
4,635	evidence_summarization	You are a clinical research expert specializing in evidence synthesis and systematic reviews. Based on the provided clinical evidence from multiple studies, please analyze the findings and select the most accurate summary of the evidence.	What is the current understanding of the impact of vitamin C supplementation on the prevention and treatment of pneumonia in children and adults? Please answer this question based on the information provided below: [Prophylactic value of vitamin C in acute respiratory tract infections in schoolchildren]. Vitamin C prophylaxis in a boarding school. The clinical effects of vitamin C supplementation in elderly hospitalised patients with acute respiratory infections. A randomised double-blind trial involving vitamin C/placebo supplementation was conducted on 57 elderly patients admitted to hospital with acute respiratory infections (bronchitis and bronchopneumonia). Patients were assessed clinically and biochemically on admission and again at 2 and 4 weeks after admission having received either 200 mg vitamin C per day, or placebo. This relatively modest oral dose led to a significant increase in plasma and white cell vitamin C concentration even in the presence of acute respiratory infection. Using a clinical scoring system based on major symptoms of the respiratory condition, patients supplemented with the vitamin fared significantly better than those on placebo. This was particularly the case for those commencing the trial most severely ill, many of whom had very low plasma and white cell vitamin C concentrations on admission. Various mechanisms by which vitamin C could assist this type of patient are discussed. Vitamin C prophylaxis in marine recruits. A prospective, randomized, double-blind study was carried out to determine whether vitamin C prophylaxis, 2.0 g/day, vs placebo prophylaxis would reduce the incidence or morbidity of the common cold and other respiratory illnesses in 674 marine recruits during an eight-week period. Whole-blood ascorbic acid levels measured six weeks after initiation of the study were significantly higher in the vitamin C group. There was no difference between the two groups in the incidence or duration of colds. The vitamin C group rated their colds as being less severe, but this was not reflected in different symptom complexes or in fewer sick-call visits or training days lost. This study and the literature do not support the prophylactic use of vitamin C to prevent the common cold. Effect of micronutrients on morbidity and duration of hospital stay in childhood pneumonia. A cross-sectional and controlled clinical trial was conducted in under-5 children to compare the effects of supplementation of five micronutrients (vitamin-A, vitamin C, vitamin E, folic acid and zinc) on the morbidity and on the duration of hospital stay in pneumonia. Data were collected from 1150 children. Among them 350 children were excluded for various reasons and finally data from 800 children were analyzed. Among these 800 children 59.00% (475) were male and 41.00% (325) were female. The mean+/-SD age was 6.5+/-5.6 months and 56.25% (450) were infants. The children were divided into two groups-400 in control group and 400 in intervention (case) group. In both the groups, specific treatment was given by ampicillin and gentamycin. In intervention group, five micronutrients were given in 200 children from the day of admission and continued up to discharge. Another 200 children were again divided into 5 sub-groups (40 in each sub-group) and a single micronutrient was given in the same way in each sub-groups. All the subjects were suffering clinically from severe pneumonia and radiologically from bronchopneumonia. Cases and controls were matched by parents' occupation, education level, economic status and family members. All the children were fully vaccinated as per existing EPI schedule of the country, partially breastfed up to six months and after six months weaned by carbohydrate rich diet. All the children were in mild (grade I) PEM according to Gomez's classification. Venous blood was collected for estimation of serum level of five micronutrients from all the samples before starting treatment by standard procedures. The average blood level of all the micronutrients was low. The average duration of hospital staying was 6.75 days in intervention group and 7.75 days in control group (p<0.01). Chest indrawing and fast breathing disappeared earlier in the intervention group (p<0.01) suggesting that supplementation of micronutrients decrease the morbidity and duration of hospital stay of children suffering from pneumonia. Options: A: Vitamin C supplementation significantly reduces the incidence and mortality of pneumonia. B: Vitamin C supplementation has a clear and well-established benefit in reducing the duration of pneumonia symptoms. C: The effect of vitamin C supplementation on the prevention and treatment of pneumonia is uncertain due to the small number of studies and very low quality of evidence. D: Vitamin C supplementation has been proven to have no effect on the prevention and treatment of pneumonia.	C

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.