Relationship between volume and outcome for gastroschisis: A systematic review.

BACKGROUND: Newborns with gastroschisis need surgery to reduce intestines into the abdominal cavity and to close the abdominal wall. Due to an existing volume-outcome relationship for other high-risk, low-volume procedures, we aimed at examining the relationship between hospital or surgeon volume and outcomes for gastroschisis. METHODS: We conducted a systematic literature search in Medline, Embase, CENTRAL, CINAHL and Biosis Previews in June 2021 and searched for additional literature. We included (cluster-) randomized controlled trials (RCTs) and prospective or retrospective cohort studies analyzing the relationship between hospital or surgeon volume and mortality, morbidity or quality of life. We assessed risk of bias of included studies using ROBINS-I and performed a systematic synthesis without meta-analysis and used GRADE for assessing the certainty of the evidence. RESULTS: We included 12 cohort studies on hospital volume. Higher hospital volume may reduce in-hospital mortality of neonates with gastroschisis, while the evidence is very uncertain for other outcomes. Findings are based on a low certainty of the evidence for in-hospital mortality and a very low certainty of the evidence for all other analyzed outcomes, mainly due to risk of bias and imprecision. We did not identify any study on surgeon volume. CONCLUSION: The evidence suggests that higher hospital volume reduces in-hospital mortality of newborns with gastroschisis. However, the magnitude of this effect seems to be heterogeneous and results should be interpreted with caution. There is no evidence on the relationship between surgeon volume and outcomes.

Measuring test-retest reliability (TRR) of AMSTAR provides moderate to perfect agreement - a contribution to the discussion of the importance of TRR in relation to the psychometric properties of assessment tools.

BACKGROUND: Systematic Reviews (SRs) can build the groundwork for evidence-based health care decision-making. A sound methodological quality of SRs is crucial. AMSTAR (A Measurement Tool to Assess Systematic Reviews) is a widely used tool developed to assess the methodological quality of SRs of randomized controlled trials (RCTs). Research shows that AMSTAR seems to be valid and reliable in terms of interrater reliability (IRR), but the test retest reliability (TRR) of AMSTAR has never been investigated. In our study we investigated the TRR of AMSTAR to evaluate the importance of its measurement and contribute to the discussion of the measurement properties of AMSTAR and other quality assessment tools. METHODS: Seven raters at three institutions independently assessed the methodological quality of SRs in the field of occupational health with AMSTAR. Between the first and second ratings was a timespan of approximately two years. Answers were dichotomized, and we calculated the TRR of all raters and AMSTAR items using Gwet's AC1 coefficient. To investigate the impact of variation in the ratings over time, we obtained summary scores for each review. RESULTS: AMSTAR item 4 (Was the status of publication used as an inclusion criterion?) provided the lowest median TRR of 0.53 (moderate agreement). Perfect agreement of all reviewers was detected for AMSTAR-item 1 with a Gwet's AC1 of 1, which represented perfect agreement. The median TRR of the single raters varied between 0.69 (substantial agreement) and 0.89 (almost perfect agreement). Variation of two or more points in yes-scored AMSTAR items was observed in 65% (73/112) of all assessments. CONCLUSIONS: The high variation between the first and second AMSTAR ratings suggests that consideration of the TRR is important when evaluating the psychometric properties of AMSTAR.. However, more evidence is needed to investigate this neglected issue of measurement properties. Our results may initiate discussion of the importance of considering the TRR of assessment tools. A further examination of the TRR of AMSTAR, as well as other recently established rating tools such as AMSTAR 2 and ROBIS (Risk Of Bias In Systematic reviews), would be useful.

Authors should clearly report how they derived the overall rating when applying AMSTAR 2-a cross-sectional study.

OBJECTIVES: A measurement tool to assess systematic reviews (SRs) 2 (AMSTAR 2) allows for deriving the overall confidence in an SR. We investigated how authors derived the overall confidence rating and whether different schemes lead to different results. STUDY DESIGN AND SETTING: We compared three different schemes (original 7-item scheme, a self-developed 5-item scheme, and the AMSTAR Web site) to derive the overall confidence in AMSTAR 2 using two distinct samples of SRs. Multiple bibliographic databases were searched for articles to analyze how AMSTAR 2 was applied by others. RESULTS: In both samples (n = 60 and n = 58), the Friedman test revealed a significant difference between the schemes (P < 0.001). The Web site scheme was the least strict one, whereas between the 5-item and 7-item scheme, no differences were found in post hoc analyses. We included 53 publications applying AMSTAR 2 identified in our literature search. Only 37 of them (70%) used the original 7-item scheme. Less than half of them (18 of 37) reported how they derived the overall rating. CONCLUSION: Authors should clearly report how they have derived the overall rating when applying AMSTAR 2. Reporting should allow for reproducing the overall ratings for editors, peer reviewers, and readers.

The methodological quality of systematic reviews on the treatment of adult major depression needs improvement according to AMSTAR 2: A cross-sectional study.

BACKGROUND: Several standards have been developed to assess methodological quality of systematic reviews (SR). One widely used tool is the AMSTAR. A recent update - AMSTAR 2 - is a 16 item evaluation tool that enables a detailed assessment of SR that include randomised (RCT) or non-randomised studies (NRS) of healthcare interventions. METHODS: A cross-sectional study of SR on pharmacological or psychological interventions in major depression in adults was conducted. SR published during 2012-2017 were sampled from MEDLINE, EMBASE and the Cochrane Database of SR. Methodological quality was assessed using AMSTAR 2. Potential predictive factors associated with quality were examined. RESULTS: In rating overall confidence in the results of 60 SR four reviews were rated "high", two were "moderate", one was "low" and 53 were "critically low". The mean AMSTAR 2 percentage score was 45.3% (standard deviation 22.6%) in a wide range from 7.1% to 93.8%. Predictors of higher quality were: type of review (higher quality in Cochrane Reviews), SR including only randomized trials and higher journal impact factor. LIMITATIONS: AMSTAR 2 is not intended to be used for the generation of a percentage score. CONCLUSIONS: According to AMSTAR 2 the overall methodological quality of SR on the treatment of adult major depression needs improvement. Although there is a high need for summarized information in the field of mental health, this work demonstrates the need to critically assess SR before using their findings. Better adherence to established reporting guidelines for SR is needed.

Relationship between volume and outcome for gastroschisis: a systematic review protocol.

BACKGROUND: Gastroschisis is a congenital anomaly that needs surgical management for repositioning intestines into the abdominal cavity and for abdominal closure. Higher hospital or surgeon volume has previously been found to be associated with better clinical outcomes for different especially high-risk, low volume procedures. Therefore, we aim to examine the relationship between hospital or surgeon volume and outcomes for gastroschisis. METHODS: We will perform a systematic literature search from inception onwards in Medline, Embase, CENTRAL, CINAHL, and Biosis Previews without applying any limitations. In addition, we will search trial registries and relevant conference proceedings. We will include (cluster-) randomized controlled trials (RCTs) and prospective or retrospective cohort studies analyzing the relationship between hospital or surgeon volume and clinical outcomes. The primary outcomes will be survival and mortality. Secondary outcomes will be different measures of morbidity (e.g., severe gastrointestinal complications, gastrointestinal dysfunctions, and sepsis), quality of life, and length of stay. We will systematically assess risk of bias of included studies using RoB 2 for individually or cluster-randomized trials and ROBINS-I for cohort studies, and extract data on the study design, patient characteristics, case-mix adjustments, statistical methods, hospital and surgeon volume, and outcomes into standardized tables. Title and abstract screening, full text screening, critical appraisal, and data extraction of results will be conducted by two reviewers independently. Other data will be extracted by one reviewer and checked for accuracy by a second one. Any disagreements will be resolved by discussion. We will not pool results statistically as we expect included studies to be clinically and methodologically very diverse. We will conduct a systematic synthesis without meta-analysis and use GRADE for assessing the certainty of the evidence. DISCUSSION: Given the lack of a comprehensive summary of findings on the relationship between hospital or surgeon volume and outcomes for gastroschisis, this systematic review will put things right. Results can be used to inform decision makers or clinicians and to adapt medical care. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework (DOI: https://doi.org/10.17605/OSF.IO/EX34M ; https://doi.org/10.17605/OSF.IO/HGPZ2 ).

Relationship between volume and outcome for surgery on congenital diaphragmatic hernia: A systematic review.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a rare and life-threatening anomaly that needs surgical therapy after clinical stabilization of the neonate. Given an existing volume-outcome relationship for other high-risk, low volume procedures, we aimed at examining the relationship between hospital or surgeon volume and outcomes for surgery on CDH. METHODS: We conducted a systematic search in multiple databases in September 2019 and searched for additional literature. We assessed risk of bias of included studies using ROBINS-I and synthesized results in a structured narrative way using GRADE. RESULTS: We included 5 cohort studies on hospital volume. Results for in-hospital mortality, one-year mortality and length of stay are inconclusive. The certainty of the evidence was very low for all outcomes, due to risk of bias, inconsistency and imprecision. We did not identify any study on surgeon volume. CONCLUSION: Due to the very low certainty of the evidence it is uncertain whether higher hospital volume is associated with favorable outcomes for neonates undergoing surgery for CDH. There is no evidence on the relationship between surgeon volume and outcomes. Future studies should use more rigorous methodology and analyze additional outcomes to allow for more meaningful inferences. LEVEL OF EVIDENCE: III SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42018090231).

A psychometric study found AMSTAR 2 to be a valid and moderately reliable appraisal tool.

OBJECTIVES: The objectives of this study were to determine the interrater reliability (IRR) of assessment of multiple systematic reviews (AMSTAR) 2 for reviews of pharmacological or psychological interventions for the treatment of major depression, to compare it to that of AMSTAR and risk of bias in systematic reviews (ROBIS), and to assess the convergent validity between the appraisal tools. STUDY DESIGN AND SETTING: Two groups of four raters were each assigned one of two samples of 30 systematic reviews. All eight raters applied AMSTAR 2 to their sample. Each group also applied either AMSTAR or ROBIS. Fleiss' kappa and Gwet's AC1 were calculated, and agreement between the tools was assessed. RESULTS: The median kappa values as a measure of IRR indicated a moderate agreement for AMSTAR 2 (median = 0.51), a substantial agreement for AMSTAR (median = 0.62), and a fair agreement for ROBIS (median = 0.27). Validity results showed a positive association for AMSTAR and AMSTAR 2 (r = 0.91) as well as ROBIS and AMSTAR 2 (r = 0.84). For the overall rating, AMSTAR 2 showed a high concordance with ROBIS and a lower concordance with AMSTAR. CONCLUSION: The IRR of AMSTAR 2 was found to be slightly lower than the IRR of AMSTAR and higher than the IRR of ROBIS. Validity measurements indicate that AMSTAR 2 is closely related to both ROBIS and AMSTAR.

Relationship between volume and outcome for congenital diaphragmatic hernia: a systematic review protocol.

BACKGROUND: Congenital diaphragmatic hernia is a rare and life-threatening anomaly that occurs during fetal development and results in an incomplete or incorrect formation of the diaphragm. Surgical therapy of the diaphragm should be performed after clinical stabilization of the neonate. Higher hospital or surgeon volume has previously been found to be associated with better clinical outcomes for different especially high-risk, low-volume procedures. Therefore, we aim to examine the relationship between hospital or surgeon volume and outcomes for congenital diaphragmatic hernia. METHODS: This systematic review protocol has been designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol. We will perform a systematic literature search in MEDLINE, Embase, CINAHL and Biosis Previews without applying any limitations. In addition, we will search for relevant conference abstracts. We will screen titles and abstracts of retrieved studies, obtain potentially relevant full texts, and assess the eligibility of those full texts against our inclusion criteria. We will include comparative studies analyzing the relationship between hospital or surgeon volume and clinical outcomes. We will systematically assess risk of bias of included studies and extract data on the study design, patient characteristics, case-mix adjustments, statistical methods, hospital and surgeon volume, and outcomes into standardized tables. Title and abstract screening, full-text screening, critical appraisal, and data extraction of results will be conducted by two reviewers independently. Other data will be extracted by one reviewer and checked for accuracy by a second one. Any disagreements will be resolved by discussion. We will not perform a meta-analysis as we expect included studies to be clinically and methodologically very diverse. We will synthesize findings from primary studies in a structured narrative way and using GRADE. DISCUSSION: Given the lack of a comprehensive summary of findings on the relationship between hospital or surgeon volume and outcomes for congenital diaphragmatic hernia, this systematic review will put things right. Results can be used to inform decision makers or clinicians and to adapt medical care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ( CRD42018090231 ).

Inter-rater reliability of AMSTAR is dependent on the pair of reviewers.

BACKGROUND: Inter-rater reliability (IRR) is mainly assessed based on only two reviewers of unknown expertise. The aim of this paper is to examine differences in the IRR of the Assessment of Multiple Systematic Reviews (AMSTAR) and R(evised)-AMSTAR depending on the pair of reviewers. METHODS: Five reviewers independently applied AMSTAR and R-AMSTAR to 16 systematic reviews (eight Cochrane reviews and eight non-Cochrane reviews) from the field of occupational health. Responses were dichotomized and reliability measures were calculated by applying Holsti's method (r) and Cohen's kappa (κ) to all potential pairs of reviewers. Given that five reviewers participated in the study, there were ten possible pairs of reviewers. RESULTS: Inter-rater reliability varied for AMSTAR between r = 0.82 and r = 0.98 (median r = 0.88) using Holsti's method and κ = 0.41 and κ = 0.69 (median κ = 0.52) using Cohen's kappa and for R-AMSTAR between r = 0.77 and r = 0.89 (median r = 0.82) and κ = 0.32 and κ = 0.67 (median κ = 0.45) depending on the pair of reviewers. The same pair of reviewers yielded the highest IRR for both instruments. Pairwise Cohen's kappa reliability measures showed a moderate correlation between AMSTAR and R-AMSTAR (Spearman's ρ =0.50). The mean inter-rater reliability for AMSTAR was highest for item 1 (κ = 1.00) and item 5 (κ = 0.78), while lowest values were found for items 3, 8, 9 and 11, which showed only fair agreement. CONCLUSIONS: Inter-rater reliability varies widely depending on the pair of reviewers. There may be some shortcomings associated with conducting reliability studies with only two reviewers. Further studies should include additional reviewers and should probably also take account of their level of expertise.

Resuming the discussion of AMSTAR: What can (should) be made better?

BACKGROUND: Evidence syntheses, and in particular systematic reviews (SRs), have become one of the cornerstones of evidence-based health care. The Assessment of Multiple Systematic Reviews (AMSTAR) tool has become the most widely used tool for investigating the methodological quality of SRs and is currently undergoing revision. The objective of this paper is to present insights, challenges and potential solutions from the point of view of a group of assessors, while referring to earlier methodological discussions and debates with respect to AMSTAR. DISCUSSION: One major drawback of AMSTAR is that it relies heavily on reporting quality rather than on methodological quality. This can be found in several items. Furthermore, it should be acknowledged that there are now new methods and procedures that did not exist when AMSTAR was developed. For example, the note to item 1 should now refer to the International Prospective Register of Ongoing Systematic Reviews (PROSPERO). Furthermore, item 3 should consider the definition of hand-searching, as the process of reviewing conference proceedings using the search function (e.g. in Microsoft Word or in a PDF file) does not meet the definition set out by the Cochrane Collaboration. Moreover, methods for assessing the quality of the body of evidence have evolved since AMSTAR was developed and should be incorporated into a revised AMSTAR tool. Potential solutions are presented for each AMSTAR item with the aim of allowing a more thorough assessment of SRs. As the AMSTAR tool is currently undergoing further development, our paper hopes to add to preceding discussions and papers regarding this tool and stimulate further discussion.

Topical treatments for scalp psoriasis.

BACKGROUND: People with chronic plaque psoriasis often have lesions on the scalp. Hair makes the scalp difficult to treat and the adjacent facial skin is particularly sensitive to topical treatments. OBJECTIVES: To assess the efficacy and safety of topical treatments for scalp psoriasis. SEARCH METHODS: We searched the following databases up to August 2015: the Cochrane Skin Group Specialised Register, CENTRAL (2015, Issue 7), MEDLINE (from 1946), EMBASE (from 1974) and LILACS (from 1982). We also searched five trials registers, screened abstracts of six psoriasis-specific conferences and checked the reference lists of included studies for further references to relevant randomised controlled trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) with a parallel-group, cross-over or within-patient design of topical treatments for people of all ages with scalp psoriasis. DATA COLLECTION AND ANALYSIS: Two authors independently carried out study selection, data extraction and 'Risk of bias' assessment. Disagreements were settled by reference to a third author.To assess the quality of evidence, we focused on the following outcomes: 'clearance' or 'response' as assessed by the investigator global assessment (IGA), improvement in quality of life, adverse events requiring withdrawal of treatment and 'response' as assessed by the patient global assessment (PGA).We expressed the results of the single studies as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes, and mean differences (MD) with 95% CI for continuous outcomes. If studies were sufficiently homogeneous, we meta-analysed the data by using the random-effects model. Where it was not possible to calculate a point estimate for a single study, we described the data qualitatively. We also presented the number needed to treat to benefit (NNTB).We categorised topical corticosteroids according to the German classification of corticosteroid potency as mild, moderate, high and very high. MAIN RESULTS: We included 59 RCTs with a total of 11,561 participants. Thirty studies were either conducted or sponsored by the manufacturer of the study medication. The risk of bias varied considerably among the included studies. For instance, most authors did not state the randomisation method and few addressed allocation concealment. Most findings were limited to short-term treatments, since most studies were conducted for less than six months. Only one trial investigated long-term therapy (12 months). Although we found a wide variety of different interventions, we limited the grading of the quality of evidence to three major comparisons: steroid versus vitamin D, two-compound combination of steroid and vitamin D versus steroid monotherapy and versus vitamin D.In terms of clearance, as assessed by the IGA, steroids were better than vitamin D (RR 1.82; 95% CI 1.52 to 2.18; four studies, 2180 participants, NNTB = 8; 95% CI 7 to 11; moderate quality evidence). Statistically, the two-compound combination was superior to steroid monotherapy, however the additional benefit was small (RR 1.22; 95% CI 1.08 to 1.36; four studies, 2474 participants, NNTB = 17; 95% CI 11 to 41; moderate quality evidence). The two-compound combination was more effective than vitamin D alone (RR 2.28; 95% CI 1.87 to 2.78; four studies, 2008 participants, NNTB = 6; 95% CI 5 to 7; high quality evidence).In terms of treatment response, as assessed by the IGA, corticosteroids were more effective than vitamin D (RR 2.09; 95% CI 1.80 to 2.41; three studies, 1827 participants; NNTB = 4; 95% CI 4 to 5; high quality evidence). The two-compound combination was better than steroid monotherapy, but the additional benefit was small (RR 1.15; 95% CI 1.06 to 1.25; three studies, 2444 participants, NNTB = 13; 95% CI 9 to 24; moderate quality evidence). It was also more effective than vitamin D alone (RR 2.31; 95% CI 1.75 to 3.04; four studies, 2222 participants, NNTB = 3; 95% CI 3 to 4; moderate quality evidence).Reporting of quality of life data was poor and data were insufficient to be included for meta-analysis.Steroids caused fewer withdrawals due to adverse events than vitamin D (RR 0.22; 95% CI 0.11 to 0.42; four studies, 2291 participants; moderate quality evidence). The two-compound combination and steroid monotherapy did not differ in the number of adverse events leading withdrawal (RR 0.88; 95% CI 0.42 to 1.88; three studies, 2433 participants; moderate quality evidence). The two-compound combination led to fewer withdrawals due to adverse events than vitamin D (RR 0.19; 95% CI 0.11 to 0.36; three studies, 1970 participants; high quality evidence). No study reported the type of adverse event requiring withdrawal.In terms of treatment response, as assessed by the PGA, steroids were more effective than vitamin D (RR 1.48; 95% CI 1.28 to 1.72; three studies, 1827 participants; NNTB = 5; 95% CI 5 to 7; moderate quality evidence). Statistically, the two-compound combination was better than steroid monotherapy, however the benefit was not clinically important (RR 1.13; 95% CI 1.06 to 1.20; two studies, 2226 participants; NNTB = 13; 95% CI 9 to 26; high quality evidence). The two-compound combination was more effective than vitamin D (RR 1.76; 95% CI 1.46 to 2.12; four studies, 2222 participants; NNTB = 4; 95% CI 3 to 6; moderate quality evidence).Common adverse events with these three interventions were local irritation, skin pain and folliculitis. Systemic adverse events were rare and probably not drug-related.In addition to the results of the major three comparisons we found that the two-compound combination, steroids and vitamin D monotherapy were more effective than the vehicle. Steroids of moderate, high and very high potency tended to be similarly effective and well tolerated. There are inherent limitations in this review concerning the evaluation of salicylic acid, tar, dithranol or other topical treatments. AUTHORS' CONCLUSIONS: The two-compound combination as well as corticosteroid monotherapy were more effective and safer than vitamin D monotherapy. Given the similar safety profile and only slim benefit of the two-compound combination over the steroid alone, monotherapy with generic topical steroids may be fully acceptable for short-term therapy.Future RCTs should investigate how specific therapies improve the participants' quality of life. Long-term assessments are needed (i.e. 6 to 12 months).

Efficacy and Safety of Systemic Long-Term Treatments for Moderate-to-Severe Psoriasis: A Systematic Review and Meta-Analysis.

Psoriasis as a chronic inflammatory disease often requires effective long-term treatment; a comprehensive systematic evaluation of efficacy and safety of systemic long-term treatments in patients with moderate-to-severe psoriasis is lacking. Twenty-five randomized clinical trials were included. Results were pooled and quality of evidence was assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). With respect to PASI 75 (psoriasis area and severity index), pooled risk ratios for infliximab (13.07, 95% confidence interval (CI): 8.60-19.87), secukinumab (11.97, 95% CI: 8.83-16.23), ustekinumab (11.39, 95% CI: 8.94-14.51), adalimumab (8.92, 95% CI: 6.33-12.57), etanercept (8.39, 95% CI: 6.74-10.45), and apremilast (5.83, 95% CI: 2.58-13.17) show superiority of biologics and apremilast in long-term therapy compared with placebo. With respect to the addressed safety parameters, no differences were seen between adalimumab, etanercept, or infliximab versus placebo. No placebo-controlled data on conventional treatments was identified. Head-to-head studies showed superior efficacy of secukinumab and infliximab versus etanercept and of infliximab versus methotrexate. A clear ranking is limited by the lack of long-term head-to-head trials. From the available evidence, infliximab, secukinumab, and ustekinumab are the most efficacious long-term treatments. Data on conventionals are insufficient. Further head-to-head comparisons and studies on safety and patient-related outcomes are needed to draw more reliable conclusions.

Online consensus conferences for clinical guidelines development - a survey among participants from the International Guidelines for the Treatment of Actinic Keratosis.

RATIONALE, AIMS AND OBJECTIVES: Guideline development requires considerable time and financial resources. New technical devices such as software for online conferences may help to reduce time and financial efforts of guidelines development. The present survey may serve as an explorative pilot for a future study to determine the technical feasibility, acceptability and possible weaknesses of online consensus conferences for clinical guidelines development. METHODS: An anonymous online survey was conducted among participants in the online consensus conference of the International League of Dermatological Societies (ILDS) Guidelines for the Treatment of Actinic Keratosis. RESULTS: The majority of participants reported no technical problems with the participation in the online consensus conference; one participant had substantial technical problems accountable to a regional telephone breakdown. The majority of participants would not have preferred a traditional face-to-face conference, and all participants rated online consensus conferences for international guidelines as absolutely acceptable. Rates of acceptance were particularly high among those participants with prior experience with consensus conferences. Certain aspects, particularly the possibilities of debating, were rated as possibly superior in face-to-face conferences by some participants. CONCLUSIONS: The data from the online survey indicate that online consensus conferences may be an appropriate alternative to traditional face-to-face consensus conferences, especially within the frame of international guidelines that would require high travel costs and time. Further research is necessary to confirm the data from this explorative pilot study.

Study of perceptions of the extent to which guideline recommendations are binding: a survey of commonly used terminology.

BACKGROUND: Doctors are more likely to implement guidelines in their everyday practice if the recommendations contained in them are understandable. So far, there has been little standardization in the wording of guideline recommendations. It would be important to know how certain terms are understood by guideline users. In this study, doctors were asked in a survey about what they considered to be the level of obligation carried by various formulations that are commonly used in guidelines to recommend particular courses of action. METHODS: An online survey of physicians (mostly dermatologists) was carried out in which they were asked to rate, on a visual analog scale, what they perceived to be the level of obligation of various common formulations for guideline recommendations. RESULTS: The terms "muss" (must) and "darf nicht" (must not) were interpreted as being maximally binding. The two closely related German words "soll" (shall) and "sollte" (should) were considered highly binding, as were negative formulations such as "wird nicht empfohlen" (is not recommended). The perceived level of obligation of "soll" did not differ from that of "sollte" to any detectable extent, nor was there any detectable distinction between the various negative formulations studied. Formulations with the words "wird empfohlen" (is recommended), "kann empfohlen werden" (can be recommended), or other "kann" (can) expressions were considered to be only mildly or moderately binding. In general, there was marked variation in the perceived level of obligation of formulations located in the low and middle ranges. CONCLUSION: These findings suggest that guideline users do not necessarily perceive recommendation strengths as the guideline authors intended. It might be better if positive recommendations came in only two different strengths, while a single recommendation strength might suffice for negative ones. Further studies should shed more light on this question.

Which antipsoriatic drug has the fastest onset of action? Systematic review on the rapidity of the onset of action.

The time necessary for a treatment to become effective is crucial for patients and physicians but has been largely neglected in the reporting and comparison of clinical trials in dermatology. The aim of this systematic review is to determine the time until the onset of action (TOA) of systemic agents approved for moderate-to-severe psoriasis. Primary outcome is the TOA defined as the weighted mean time until 25% of the patients achieved a psoriasis area and severity index (PASI) 75 response. Among the biologics, infliximab has the shortest TOA (3.5 weeks), followed by ustekinumab (high dose 4.6/low dose 5.1 weeks/not weight adapted), adalimumab (4.6 weeks), etanercept (high dose 6.6/low dose 9.5 weeks), and alefacept (high dose 15.4 weeks/low dose: no data). Among the conventional treatments, good data are available for cyclosporine A (CsA; TOA: 6.0 weeks) and limited data are found for methotrexate (MTX; TOA: high dose 3.2/low dose 9.9 weeks). No data are available for fumaric acid esters and retinoids. This systematic review provides clinically relevant information on the onset of action of antipsoriatic agents, although the data currently available allow only a limited assessment. Psoriasis trials should consider including TOA as an additional outcome measure.

Methodological standards in medical reporting.

Published research findings are the basis for health care decisions or further medical research. However, reporting of research methods and findings is often incomplete and of insufficient quality. Poor reporting hampers the assessment of reliability and validity of study results. Strengths and weaknesses of the investigation cannot be completely evaluated and subsequently it can mislead decision making in health care or in further clinical research. Transparent reporting can help minimize misinterpretation of publications. Several guidelines were developed to provide advice for reporting research methods and findings. These reporting guidelines facilitate critical appraisal and interpretation of the studies. The guidelines specify in form of checklists a minimum set of items required for clear and transparent reporting. The checklists focus on design, conduct and analysis of studies in particular issues that might introduce bias into the research. The application of these reporting guidelines is required by many international journals. In this CME article we present guidelines for reporting of randomized controlled trials (CONSORT), observational studies (STROBE) and systematic reviews and meta-analyses (PRISMA, MOOSE).

The OTSC®-clip in revisional endoscopy against weight gain after bariatric gastric bypass surgery.

The maintenance of the restrictive component of the Fobi pouch gastric bypass is essential for permanent weight control. Dilatation of the pouch-outlet and of the pouch itself is responsible for substantial weight gain by an increased volume per meal and binge-eating due to the rapid emptying. An endoscopic over-the-scope clip (OTSC®; Ovesco AG, Tübingen, Germany) was applied in 94 patients following gastric bypass and unintended weight gain by dilated gastro-jejunostomy to narrow the pouch-outlet. The OTSC®-clip application was safe and efficient to reduce the pouch-outlet in all cases. Best clinical results were obtained by narrowing the gastro-jejunostomy by placing two clips at opposite sites, hence reducing the outlet of more than 80%. Preferably, the clip approximated the whole thickness of the wall to avoid further dilatation of the anastomosis. Between surgery and OTSC®-clip application the mean BMI dropped from 45.8 (±3.6) to 32.8 (±1.9). At the first follow-up about 3 months (mean 118 days, ±46 days) after OTSC®-clip application the mean BMI was 29.7 (±1.8). At the second follow-up about 1 year (mean 352 days, ±66 days) after OTSC®-clip application the mean BMI was 27.4 (±3.8). The OTSC®-clip for revisional endoscopy after gastric bypass is reliable and effective in treating weight gain due to a dilated pouch-outlet with favorable short- and midterm results.

Efficacy of isoflavones in relieving vasomotor menopausal symptoms - A systematic review.

This review assessed the efficacy of isoflavone supplements to reduce vasomotor symptoms in menopausal women by reviewing all published randomized controlled trials. Systematic literature searches were carried out in 70 databases. Randomized and placebo controlled studies were included if they investigated the treatment of isoflavone supplements derived from soy or red clover on vasomotor symptoms in peri- or postmenopausal women for at least 12 wks. Data were analyzed concerning outcome and methodological quality of the study. Twenty-three trials met the inclusion criteria, thereof 17 investigated soy isoflavones and 6 red clover isoflavones. Without exception, selected trials examining the effect of red clover isoflavones were already assessed in several meta-analyses and were therefore excluded from this evaluation. As the soy isoflavone studies were very heterogeneous concerning interventions and outcome measures, meta-analysis could not be performed and trials were systematically assessed in a structured approach. Included soy isoflavone studies had numerous quality deficiencies and did not consistently show a reduction of flushes after treatment with soy isoflavones. Therefore, there is no conclusive evidence, but only some indication of a benefit of soy isoflavones on hot flush frequency or severity.