Gynaecologic surgery from uncertainty to science: evidence-based surgery is no passing fad

BACKGROUND: The randomized controlled trial (RCT) is the least biased measure of the effectiveness of interventions, including surgical interventions. The aim was to review the available evidence base in gynaecologic surgery, to assess what progress has been made and to determine gaps in the evidence for clinical decision-making. METHODS: Systematic reviews involving gynaecological surgery interventions were extracted from the Cochrane Database of Systematic Reviews (Issue 2, 2007) and data were extracted for key primary outcomes from each of the randomized trials in the reviews. The reviews were categorized as to whether they had provided evidence of effectiveness for pre-defined outcomes of most relevance to patients. RESULTS: Of 371 reviews or protocols published on the Cochrane Database of Systematic Reviews (Issue 2, 2007), only 30 were completed reviews assessing surgical interventions. Seven reviews concluded there was evidence of a significant effect (whether beneficial or harmful) of the interventions studied for pre-defined primary outcomes; 11 reviews concluded there was some evidence of significant effects for primary outcomes along with some gaps for primary outcomes; 12 reviews concluded insufficient evidence of effectiveness. Common themes of unique methodological challenges and pitfalls with trials of surgical interventions were apparent. CONCLUSIONS: Cochrane reviews have gone a long way to establishing a sound evidence base in gynaecologic surgery: some gaps in the evidence have been eliminated and others highlighted. In general, gynaecology has been a specialty where surgical interventions have been well exposed to the scrutiny of RCTs compared with other surgical specialties.     

Vasectomy techniques for male sterilization: systematic Cochrane review of randomized controlled trials and controlled clinical trials

BACKGROUND: The review aimed to compare the effectiveness, safety and acceptability of vasectomy techniques for male sterilization. METHODS: We searched five computerized databases and reference lists of relevant articles and book chapters for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing vasectomy techniques. Two reviewers independently extracted data from eligible articles. RESULTS: Two poor-quality trials compared vas occlusion with clips versus a conventional technique, and four poor-quality trials examined vas irrigation with water versus no irrigation or irrigation with euflavine. No significant differences regarding the primary outcome of time to azoospermia were found. However, one trial reported fewer median number of ejaculations to azoospermia with euflavine rather than water irrigation. An interim report of a high-quality trial comparing vasectomy with and without fascial interposition found more azoospermia with fascial interposition but also more surgical difficulties. CONCLUSIONS: No conclusions can be reached regarding the effectiveness, safety and acceptability of vas occlusion techniques or vas irrigation since only low-quality, underpowered studies were available. Fascial interposition had improved vasectomy success but also increased surgical difficulty. High-quality, adequately reported RCTs are required. More work is also needed in the standardization of follow-up protocols, evaluation of vasectomy success and failure, recanalization and analytical methods.     

Continuous versus cyclic use of combined oral contraceptives for contraception: systematic Cochrane review of randomized controlled trials

BACKGROUND: With the recent US Food and Drug Administration approval of a combination oral contraceptive that causes a withdrawal bleed every 3 months instead of monthly, avoidance of menstruation through extended or continuous administration (>28 days of active pills) of combined oral contraceptives may become more commonplace for reasons of personal preference rather than limited to treatment of menstrual-associated medical disorders. METHODS: The review aimed to compare contraceptive efficacy, compliance, continuation, satisfaction, bleeding profiles, and menstrual symptoms of combined oral contraceptives with continuous dosing (>28 days of active pills) versus traditional cyclic dosing (21 days of active pills and 7 days of placebo). We searched five computerized databases as well as reference lists of relevant articles for randomized controlled trials (RCT) using continuous or extended combined oral contraceptives for contraception. Two reviewers independently extracted data from eligible articles. RESULTS: Six RCT met inclusion criteria and were of good quality. Contraceptive efficacy and compliance were similar between groups. Discontinuation overall, and for bleeding problems, was not uniformly higher in either group. When studied, participants reported high satisfaction with both dosing regimens. Five out of the six studies found that bleeding patterns were either equivalent or improved with continuous-dosing regimens. The continuous-dosing group had greater improvement of menstrual-associated symptoms (headaches, genital irritation, tiredness, bloating, and menstrual pain). CONCLUSIONS: The variations in pill type and time-interval for continuous dosing make direct comparisons between regimens unfeasible. To allow for comparisons, future studies should choose a previously researched pill and dosing regimen. More attention needs to be directed towards participant satisfaction and menstruation-associated symptoms.     

Effective treatment of subfertility: introducing the Cochrane Menstrual Disorders and Subfertility Group.

The last two decades have seen a rapid explosion in research surrounding subfertility treatments. This ever-increasing volume of research has made it a difficult task for health professionals involved in the management of the subfertility to be able to assimilate the information easily. There is an urgent need for the findings from research to be synthesized into simple easy to read reviews that are both of a high quality and are based on the best evidence available. The Menstrual Disorders and Subfertility Group of the Cochrane Collaboration is attempting to address these issues by collecting a register of all the randomized controlled trials in the field of reproductive medicine and preparing systematic reviews on topics that will be of interest to healthcare workers and consumers. Readers are invited to participate in this process by identifying published and unpublished data and by helping in the process of preparing protocols and systematic reviews for inclusion in the Cochrane Library.     

Bringing Parenting Interventions Back to the Future: How Randomized Microtrials May Benefit Parenting Intervention Efficacy

A novel approach is needed to promote the efficacy of parenting interventions designed to improve children's mental health. The proposed approach bridges developmental and intervention science to test which intervention elements contribute to parenting intervention program efficacy. The approach encourages the field to move “back to the future” using stringent, focused experimental techniques to test discrete parenting techniques (e.g., praise, time‐out) on their merit. We argue that these randomized microtrials are needed to (a) distinguish between the less and more efficacious elements of parenting interventions, (b) illuminate for whom and under what conditions elements are efficacious, and (c) explore the potential for empirically supported tailoring of interventions to meet families’ specific needs.     

The impact of selenium administration on severe sepsis or septic shock: a meta-analysis of randomized controlled trials

IntroductionThe efficacy of selenium administration to treat severe sepsis or septic shock remains controversial. We conduct a systematic review and meta-analysis to explore the impact of selenium administration on severe sepsis or septic shock.MethodsWe search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2020 for randomized controlled trials (RCTs) assessing the effect of selenium administration on severe sepsis or septic shock. Meta-analysis is performed using the random-effect model.ResultsFive RCTs involving 1482 patients are included in the meta-analysis. Overall, compared with control group in septic patients, selenium administration is not associated with reduced 28-day mortality (RR=0.93; 95% CI=0.73 to 1.19; P=0.58), but results in substantially decreased all-cause mortality (RR=0.78; 95% CI=0.63 to 0.98; P=0.03) and length of hospital stay (MD=-3.09; 95% CI=-5.68 to -0.50; P=0.02).ConclusionSelenium administration results in notable decrease in all-cause mortality and length of hospital stay, but shows no substantial influence on the 28-day mortality, length of ICU stay, duration of vasopressor therapy, the incidence of acute renal failure, adverse events, and serious adverse events for septic patients.     

Luteal phase support in infertility treatment: a meta-analysis of the randomized trials

BACKGROUND: The addition of GnRH agonist to the treatment regimen in women undergoing IVF cycles is thought to create a luteal phase defect. In an attempt to correct for this, many practitioners supplement with a variety of steroid hormones in the luteal phase. METHODS: To determine whether luteal phase support increases reproductive success in modern IVF cycles, a systematic review of the literature was performed. Meta-analyses were conducted when multiple homogeneous studies addressed a single issue. Only randomized controlled trials were included in the data analysis. The efficacy of supplementation, as well as the optimal route, formulation, dose, and length of administration were queried. RESULTS: Luteal supplementation with either i.m. hCG or i.m. progesterone significantly improved fertility outcomes compared with no treatment. When comparing i.m. progesterone with i.m. hCG, no fertility differences were found. Intramuscular progesterone conferred the most benefit compared with oral or vaginal use. Addition of oral estrogen to progesterone also improved implantation rates. CONCLUSION: Given the increased risk of ovarian hyperstimulation syndrome associated with hCG use, i.m. progesterone is favoured for luteal phase supplementation with the addition of estrogen.     

针灸治疗女性压力性尿失禁:随机对照研究特点分析

背景:众多文献对针灸治疗压力性尿失禁进行综述分析,但存在中外文献数据库检索不全面或没有针对性分析针灸对女性患者的单独疗效等局限性.目的:对针灸治疗压力性尿失禁临床研究各特点进行分析,为针灸临床提供参考.方法:检索从建库截止至2020-03-15 PubMed、Embase、Cochrane Library、Clinic...     

Psychological interventions decrease unintended pregnancies: A meta-analysis of randomized controlled trials

Objective

Despite innovations in contraceptive methods, unintended pregnancies remain common. Researchers have examined psychological approaches to decrease unintended pregnancies through contraceptive use. These interventions have involved applying aspects of social cognitive theory, the health belief model and self-determination theory. Research findings on the effects of these psychological approaches show conflicting evidence. The aim of this meta-analysis was to clarify the impact of these psychological interventions on unintended pregnancies

Design

Meta-analysis of randomized controlled trials (RCTs) of psychological interventions intended to prevent unwanted pregnancies through an increase in the use of contraceptive methods

Methods

A systematic search of databases and article reference lists led to 26 relevant RCTs with a total of 31,222 participants

Results

The odds ratio for pregnancy in the psychological intervention condition = .83, 95% CI [.75, .93]. The results also showed that the longer an intervention's follow-up period was, the less the prevention effect. Quality assessment of included studies indicated that all used a treatment manual and reported attrition. It also showed that most studies reported the reasons for drop-out and assessed the facilitators' adherence to the intervention protocol. The proportion of variability due to chance amongst studies was I² = 22%. Duval and Tweedie's Trim and Fill showed a difference between the observed and the adjusted values. The adjusted value, representing a conservative estimate of effect size, was OR = .891, 95% CI [.777, .999]

Conclusions

Altogether, these results support the efficacy of psychological interventions aimed at preventing unintended pregnancy through contraception.     

The efficiency and safety of trastuzumab for advanced gastric and gastroesophageal cancer: a meta-analysis of five randomized controlled trials

A meta-analysis was performed to examine the efficiency and safety of trastuzumab in patients with advanced gastric and gastroesophageal cancer (AGC). By searching multiple databases from 1990 to March 2016, all randomized controlled trials (RCTs) which compared the effect of trastuzumab-combined chemotherapy (TC) versus chemotherapy alone (CT) in gastric cancer would be included. Five RCTs with a total of 875 patients were included. Trastuzumab can improve the overall survival (OS) rate, progression-free survival (PFS), one-year survival rate, two-year survival rate and overall response rate (ORR) of patients with AGC. There were no difference between the two arms in terms of grade 3/4 adverse effects, such as vomiting, nausea, neutropenia, thrombocytopaenia and anemia. Diarrhea increased in TC group. Trastuzumab can significantly improve the survival rate, PFS, ORR of patients with AGC. It is safe and feasible and can be tolerated. It needs further prospective multinational multicenter RCTs with large samples to define the clinical benefits of trastuzumab.     

How to design and evaluate randomized controlled trials in immunotherapy for allergic rhinitis: an ARIA-GA(2) LEN statement

Specific immunotherapy (SIT) is one of the treatments for allergic rhinitis. However, for allergists, nonspecialists, regulators, payers, and patients, there remain gaps in understanding the evaluation of randomized controlled trials (RCTs). Although treating the same diseases, RCTs in SIT and pharmacotherapy should be considered separately for several reasons, as developed in this study. These include the severity and persistence of allergic rhinitis in the patients enrolled in the study, the problem of the placebo, allergen exposure (in particular pollen and mite), the analysis and reporting of the study, the level of symptoms of placebo-treated patients, the clinical relevance of the efficacy of SIT, the need for a validated combined symptom-medication score, the differences between children and adults and pharmacoeconomic analyses. This statement reviews issues raised by the interpretation of RCTs in sublingual immunotherapy. It is not possible to directly extrapolate the rules or parameters used in medication RCTs to SIT. It also provides some suggestions for the research that will be needed. Interestingly, some of the research questions can be approached with the available data obtained from large RCTs.     

Infertility:Treatment of male infertility: is it effective? Review and meta-analyses of published randomized controlled trials

There are few widely accepted treatments for male subfertility.Controlled trials are necessary to evaluate different subfertilitytreatments because pregnancies and spontaneous improvementsin semen parameters occur without treatment. Properly randomizedtrials can find out whether pregnancy rates are higher or lowerthan expected after treatment. Quantitative meta-analysis improvesprecision where individual trials are not powerful enough todemonstrate moderate treatment effects. Only 174 published randomizedtreatment trials for male subfertility were found after extensiveliterature review, both by computerized search and hand searchesof 41 journals. In 72 of the studies, pregnancy was an outcomemeasure and these are analysed and discussed. The quality ofmost trials is poor. Meta-analysis was possible on seven themes,but the results of this exercise appear to be unduly influencedby trials of poor quality. Few conventional treatments (i.e.those not involving assisted conception techniques) result inimproved fertility rates.     

Impact and costs of incentives to reduce attrition in online trials: two randomized controlled trials

Background

Attrition from follow-up is a major methodological challenge in randomized trials. Incentives are known to improve response rates in cross-sectional postal and online surveys, yet few studies have investigated whether they can reduce attrition from follow-up in online trials, which are particularly vulnerable to low follow-up rates.

Objectives

Our objective was to determine the impact of incentives on follow-up rates in an online trial.

Methods

Two randomized controlled trials were embedded in a large online trial of a Web-based intervention to reduce alcohol consumption (the Down Your Drink randomized controlled trial, DYD-RCT). Participants were those in the DYD pilot trial eligible for 3-month follow-up (study 1) and those eligible for 12-month follow-up in the DYD main trial (study 2). Participants in both studies were randomly allocated to receive an offer of an incentive or to receive no offer of an incentive. In study 1, participants in the incentive arm were randomly offered a £5 Amazon.co.uk gift voucher, a £5 charity donation to Cancer Research UK, or entry in a prize draw for £250. In study 2, participants in the incentive arm were offered a £10 Amazon.co.uk gift voucher. The primary outcome was the proportion of participants who completed follow-up questionnaires in the incentive arm(s) compared with the no incentive arm.

Results

In study 1 (n = 1226), there was no significant difference in response rates between those participants offered an incentive (175/615, 29%) and those with no offer (162/611, 27%) (difference = 2%, 95% confidence interval [CI] –3% to 7%). There was no significant difference in response rates among the three different incentives offered. In study 2 (n = 2591), response rates were 9% higher in the group offered an incentive (476/1296, 37%) than in the group not offered an incentive (364/1295, 28%) (difference = 9%, 95% CI 5% to 12%, P < .001). The incremental cost per extra successful follow-up in the incentive arm was £110 in study 1 and £52 in study 2.

Conclusion

Whereas an offer of a £10 Amazon.co.uk gift voucher can increase follow-up rates in online trials, an offer of a lower incentive may not. The marginal costs involved require careful consideration.

Trial registration

ISRCTN31070347; http://www.controlled-trials.com/ISRCTN31070347 (Archived by WebCite at http://www.webcitation.org/5wgr5pl3s)     

Laparoscopic surgery is not inherently dangerous for patients presenting with benign gynaecologic pathology. Results of a meta-analysis

BACKGROUND: Laparoscopic surgery presents a large number of advantages over laparotomy. The goal of this work was to check whether these benefits outweigh any greater risk of complications. METHODS: The study design was a meta-analysis of published data from prospective randomized clinical trials (RCT). For the period 1966 to June 2000 we searched Medline and Cochrane Controlled Trial Registers and asked the investigators for further details. Meta-analysis was carried out with the Cochrane review manager software RevMan 4.1. RESULTS: A total of 27 prospective RCT including 3611 women (1809 treated by operative laparoscopy and 1802 treated by laparotomy) were enrolled in the meta-analysis. The overall risk of complications was significantly lower for patients operated by laparoscopic surgery [relative risk (RR) 0.59; 95% confidence interval (CI) 0.50-0.70]. There was no statistically significant difference concerning the risk of major complications with respect to the approach used (RR 1.0; 95% CI 0.60-1.65). The risk of minor complications was significantly lower for patients operated by laparoscopic surgery (RR 0.55; 95% CI 0.45-0.66). Concerning the risks of readmission, second procedure and blood transfusion, there was no difference between the two groups. Identical results were found when we performed a sensitivity analysis including or excluding studies according to the methodological score. Subgroup analysis according to how serious the surgery was (minor, major, advanced) showed a significant increase in the risk of transfusion for advanced procedures performed by laparotomy. CONCLUSIONS: Laparoscopic surgery is not inherently dangerous for patients presenting benign gynaecological pathologies. The potential risk of complications should no longer be advanced as an argument against using laparoscopic surgery rather than laparotomy for an operation when the indication allows the choice.     

Efficacy of hypnosis in adults undergoing surgery or medical procedures: A meta-analysis of randomized controlled trials

This meta-analysis investigates the efficacy of hypnosis in adults undergoing surgical or medical procedures compared to standard care alone or an attention control. Through a comprehensive literature search N = 34 eligible randomized controlled trials (RCTs) were included, comprising a total of 2597 patients. Random effects meta-analyses revealed positive treatment effects on emotional distress (g = 0.53, CI 95% [0.37; 0.69]), pain (g = 0.44, CI 95% [0.26; 0.61]), medication consumption (g = 0.38, CI 95% [0.20; 0.56]), physiological parameters (g = 0.10, CI 95% [0.02; 0.18]), recovery (g = 0.25, CI 95% [0.04; 0.46]), and surgical procedure time (g = 0.25, CI 95% [0.12; 0.38]). In conclusion, benefits of hypnosis on various surgically relevant outcomes were demonstrated. However, the internal validity of RCTs seems limited and further high methodological quality RCTs are needed to strengthen the promising evidence of hypnosis for adults undergoing surgery or medical procedures.     

Update of sarilumb to treat rheumatoid arthritis based on randomized clinical trials: a systematic review

Introduction: Sarilumab is a human monoclonal antibody against Interleukin 6 α (IL-6α) receptor. Compared to tocilizumab, another IL-6 α receptor antibody, sarilumab has a different structure and higher affinity.

Areas covered: In a systematic literature review, we examined all sarilumab randomized clinical trials (RCTs) in rheumatoid arthritis. The 6 reviewed RCTs included patients who were inadequate MTX, DMARD and/or TNFi responders. Sarilumab 150–200 mg every 2 weeks improved RA signs, symptoms, function and decreased radiological progression up to 52 weeks. The most common adverse events were infections and neutropenia, the latter of which will require careful observation in future trials.

Examination of the effect of sero-positivity, disease duration, presence of erosions, use of previous biologic and comparisons to other biologics etc are still needed to complete understanding of this drug’s profile. Long term studies, too, will be needed to assess long term tolerability

Expert commentary: Results support the use of sarilumab to treat RA patients with inadequate response to MTX, other DMARDs and TNFis, although further studies are needed to fully assess its toxicity and understand the specific place of sarilumab in the RA armamentarium.     

中药治疗冠心病室性早搏随机对照试验的系统评价

目的评价中药治疗冠心病室性早搏的有效性和安全性。方法根据Cochrane协作网系统评价方法,全面检索中国期刊全文数据库（CNKI,包库）、维普中文期刊数据库（VIP）、万方学术期刊全文数据库、中国生物医学文献服务系统（CBM）、中国生物医学期刊引文数据库（CMCI/CMCC整合版）、以及中医药、中西医结合在线数据库。筛选文献,评价质量,提取资料,并用RevMan5.1软件进行Meta分析。结果纳入8篇随机对照试验,1306例患者,所有试验改良Jadad质量评分≥4分。室性期前收缩疗效：参松养心胶囊优于美西律[RR=1.39,95%CI（1.14,1.69）,P=0.001],参松养心胶囊优于心律宁[RR=1.37,95%CI（1.18,1.69）,P〈0.0001]。中医证候疗效：参松养心胶囊优于心律宁[RR=1.34,95%CI（1.21,1.49）,P〈0.001],复脉颗粒优于美西律[RR=2.17,95%CI（1.37,3.43）,P=0.001]。心电图疗效：参松养心胶囊优于心律宁[RR=1.48,95%CI（1.15,1.90）,P=0.002]。不良反应共13例,主要为恶心、食欲不振等胃肠道症状,未发现肝、肾功能异常。结论参松养心胶囊等中药能有效地改善冠心病室性期前收缩,而且安全可靠。     

Efficacy of mometasone furoate nasal spray in the treatment of allergic rhinitis. Meta-analysis of randomized, double-blind, placebo-controlled, clinical trials

Rationale: Several randomized, double‐blind, placebo‐controlled clinical trials have demonstrated the efficacy of mometasone furoate nasal spray (MFNS) in the treatment of allergic rhinitis (AR) thus allowing for a meta‐analysis to determine the overall treatment effect. Methods: A comprehensive search of the MEDLINE, LILACS, SCOPUS, and the Cochrane Library databases up to 31 October, 2007 was carried out. Randomized, double‐blind, placebo‐controlled, clinical trials evaluating the efficacy of MFNS in patients with AR compared to placebo were included. Total nasal symptom scores (TNSS), individual nasal symptoms, total non‐nasal symptom scores (TNNSS) and nasal airflow were analysed as the standardized mean difference (SMD). Meta‐analysis was performed with the random or the fixed effect models depending on heterogeneity, by using revman 5 software. Data synthesis: Sixteen of the 113 identified articles met the inclusion criteria. For MFNS efficacy on TNSS, 2998 participants were analysed: 1534 received MFNS and 1464 placebo. Mometasone furoate nasal spray was associated with a significant reduction in TNSS (SMD ?0.49, 95% CI: ?0.60 to ?0.38; P < 0.00001; I² = 50.1%). A significant effect on SMD for nasal stuffiness/congestion (?0.41; 95% CI: ?0.56 to ?0.27), rhinorrhoea (?0.44; 95% CI: ?0.66 to ?0.21), sneezing (?0.40; 95% CI: ?0.57 to ?0.23) and nasal itching (?0.39; 95% CI: ?0.53 to ?0.25) was also demonstrated. Mometasone furoate nasal spray treated subjects also showed a significant reduction in TNNSS (?0.30; 95% CI: ?0.43 to ?0.18). The proportion of patients with adverse events was similar for MFNS and placebo (0.99; 95% CI: 0.81–1.20; P = 0.91). Conclusions: This meta‐analysis provides a level Ia evidence for the efficacy of MFSN in the treatment of AR vs placebo. Adverse events frequency was similar in both groups.     

Cross-sectional study of the quality of randomized control trials on problem-based learning in medical education

Problem-based learning (PBL) is increasingly being used in medical education globally, but its effectiveness in teaching remains controversial. A randomized controlled trial (RCT) is the method of choice for evaluating its effectiveness. The quality of an RCT has a significant effect on this evaluation, but to date we have not seen an assessment of the quality of RCTs for PBL. Two researchers searched MEDLINE and EMBASE for RCTs addressing PBL in medical education. The overall quality of each report was measured on a 28-point overall quality score (OQS) based on the 2010 revised Comprehensive Standards for Reporting and Testing (CONSORT) Statement. Furthermore, to study the key factors affecting OQS more effectively, a linear regression model of those factors was established using SPSS. After literature screening, 30 RCTs were eventually included and analyzed. The median OQS was 15 (range, 7–20), which meant that half of the items in the revised 2010 CONSORT statement were poorly reported in at least 40% of the RCTs analyzed. The regression model showed that the year of publication of RCTs and the impact factors of the journals in which they were published were the main factors affecting OQS. The overall quality of reporting of RCTs on PBL teaching in medical education was not satisfactory. Some RCTs were subjectively selective in reporting certain items, leading to heterogeneity in quality. It is expected that statisticians will develop new standards more suitable for evaluating RCTs related to teaching research and that editors and peer reviewers will be required to review the relevant RCTs more strictly.