Reports Of Randomized Controlled Trials Research Articles

Sodium glucose co-transporter 2 inhibitors for glycemic control in type 2 diabetes mellitus: Quality of reporting of randomized controlled trials.

Background:Sodium glucose co-transporter 2 inhibitors represent a novel class of antidiabetic drugs. The reporting quality of the trials evaluating the efficacy of these agents for glycemic control in type 2 diabetes mellitus has not been explored. Our aim was to assess the reporting quality of such randomized controlled trials (RCTs) and to identify the predictors of reporting quality.Materials and Methods:A systematic literature search was conducted for RCTs published till 12 June 2014. Two independent investigators carried out the searches and assessed the reporting quality on three parameters: Overall quality score (OQS) using Consolidated Standards of Reporting Trials (CONSORT) 2010 statement, Jadad score and intention to treat analysis. Inter-rater agreements were compared using Cohen's weighted kappa statistic. Multivariable linear regression analysis was used to identify the predictors.Results:Thirty-seven relevant RCTs were included in the present analysis. The median OQS was 17 with a range from 8 to 21. On Jadad scale, the median score was three with a range from 0 to 5. Complete details about allocation concealment and blinding were present in 21 and 10 studies respectively. Most studies lacked an elaborate discussion on trial limitations and generalizability. Among the factors identified as significantly associated with reporting quality were the publishing journal and region of conduct of RCT.Conclusions:The key methodological items remain poorly reported in most studies. Strategies like stricter adherence to CONSORT guidelines by journals, access to full trial protocols to gain valuable information and full collaboration among investigators and methodologists might prove helpful in improving the quality of published RCT reports.

Quality of reporting randomized controlled trials (RCTs) in diabetes in Iran; a systematic review.

ObjectiveTo determine the quality of randomized controlled clinical trial (RCT) reports in diabetes research in Iran.DesignSystematized review.MethodsWe included RCTs conducted on diabetes mellitus in Iran. Animal studies, educational interventions, and non-randomized trials were excluded. We excluded duplicated publications reporting the same groups of participants and intervention. Two independent reviewers identify all eligible articles specifically designed data extraction form. We searched through international databases; Scopus, ProQuest, EBSCO, Science Direct, Web of Science, Cochrane Library, PubMed; and national databases (In Persian language) such as Magiran, Scientific Information Database (SID) and IranMedex from January 1995 to January of 2013 Two investigators assessed the quality of reporting by CONSORT 2010 (Consolidated Standards of Reporting Trials) checklist statemen.t,. Discrepancies were resolved by third reviewer consulting.ResultsOne hundred and eight five (185) studies were included and appraised. Half of them (55.7 %) were published in Iranian journals. Most (89.7 %) were parallel RCTs, and being performed on type2 diabetic patients (77.8 %). Less than half of the CONSORT items (43.2 %) were reported in studies, totally. The reporting of randomization and blinding were poor. A few studies 15.1 % mentioned the method of random sequence generation and strategy of allocation concealment. And only 34.8 % of trials report how blinding was applied.ConclusionsThe findings of this study show that the quality of RCTs conducted in Iran in diabetes research seems suboptimal and the reporting is also incomplete however an increasing trend of improvement can be seen over time. Therefore, it is suggested Iranian researchers pay much more attention to design and methodological quality in conducting and reporting of diabetes RCTs.Electronic supplementary materialThe online version of this article (doi:10.1186/s40200-016-0258-2) contains supplementary material, which is available to authorized users.

Operative versus nonoperative interventions for common fractures of the clavicle: a meta-analysis of randomized controlled trials

The popularity of surgery for acute displaced midshaft clavicle fractures has been fuelled by early randomized controlled trials (RCTs) showing improved rates of radiographic union and perceived functional benefits compared with nonoperative approaches. We performed a meta-analysis to determine the effect of operative and nonoperative interventions on the risk of secondary operation and complications and on long-term function. We search MEDLINE, Embase and the Cochrane Central Register of Controlled Trials for reports of relevant RCTs published to Mar. 7, 2014. Two reviewers assessed eligibility of potential reports and the risk of bias of included trials. The Grading of Recommendations Assessment, Development and Evaluation approach was used to summarize the quality of evidence for all outcomes. We included 15 RCTs (9 trials comparing operative and nonoperative interventions, 5 comparing implants for operative treatment, and 1 comparing nonoperative treatments). Nonoperative treatments did not differ from operative treatments in the risk of secondary operation (risk ratio [RR] 1.16, 95% confidence interval [CI] 0.58 to 2.35) or all complications (RR 0.90, 95% CI 0.55 to 1.50). One in 4 patients had a complication regardless of the treatment approach. Differences in functional outcomes, although smaller than the threshold for minimal important differences at 1 year, favoured operative interventions (standardized mean difference 0.38, 95% CI 0 to 0.75). Evidence for the type of implant or approach to nonoperative treatment remained inconclusive. Current evidence does not support the routine use of internal fixation for the treatment of displaced midshaft clavicle fractures. Complication rates were high regardless of the treatment approach.

Protocol registration and selective outcome reporting in recent psychiatry trials: new antidepressants and cognitive behavioural therapies.

The selective reporting of favorable outcomes has a serious influence on our evidence base. However, this problem has not yet been systematically investigated in the field of psychiatry. Our study aimed to evaluate registration and outcome reporting in randomized controlled trials (RCTs) of standard treatments for depression: cognitive behavioural therapy (CBT) or new-generation antidepressants (ADs). We searched for reports of RCTs examining the efficacy of CBT or AD for depression that were published between 2011 and 2013. We then compared their primary outcomes in the trial registries and those in publications. We identified 170 trials. Among them, 92 trials (54.1%) were registered, 43 trials (25.3%) were properly registered, and only 32 (18.8%) trials were both properly registered and reported (the primary outcomes as recorded in the registries were reported in publications). There was no statistically significant difference in the proportions of properly registered and reported trials for CBT or AD (relative risk: 0.51, 95% CI: 0.25-1.03). High impact factor journals, commercial funding, publication of protocol, and relatively large sample size were significant predictors of proper registration and reporting. The prevalence of proper registration and reporting is still very low in depression trials.

CONSORT in China: past development and future direction.

The Consolidated Standards of Reporting Trials (CONSORT) Statement was published in 1996, and first introduced to China in 2001. Although CONSORT has been widely accepted in high-quality international journals, we still need to have more investigation on how many Chinese journals have adopted the CONSORT Statement, and whether the quality of reporting has improved. A systematic search of the “Instructions to authors” in all Chinese medical journals in China Academic Journals (CAJ) Full-text Database was conducted up to February 2012 and only 7 journals officially listed the requirements of the CONSORT Statement. The research articles about randomized controlled trials (RCTs) published in 2002, 2004, 2006, 2008, and 2010 from journals which had specifically adopted the CONSORT Statement, and from 30 top journals based on the Chinese Science Citation Index (CSCI) 2011 as the control group, were identified. The quality of both cohorts of articles was assessed using the revised CONSORT Checklist and Jadad scale. A total of 1221 Chinese medical journals was identified. Only seven journals stated clearly in the “Instructions to authors” that authors should adopt the CONSORT requirement in the clinical trial paper. None of these journals is among the control group in the CSCI 2011. In the selected years, a total of 171 articles from 7 journals which had adopted CONSORT and 232 articles in the control were identified as including RCT trials. The average scores according to the revised CONSORT Checklist were 29.47 for the CONSORT-adopting journals and 25.57 for the control group; while the average scores based on the Jadad scale were 2.53 for CONSORT-adopting journals and 1.97 for the control group. Few journals among Chinese medical journals have adopted the CONSORT Statement. The overall quality of RCT reports in the 7 journals which have adopted CONSORT was better than those in the top 30 journals which have not adopteded CONSORT. The quality of RCT reports in Chinese journals needs further improvement, and the CONSORT Statement could be a very helpful guideline.

Quality evaluation of randomized controlled trials reports of laparoscopy compared with open colorectal resection for colorectal cancer

Objectives: Previously, there were no data looking at the quality evaluation of randomized controlled trials (RCTs) on effect comparison of laparoscopic surgery and open surgery for colorectal cancer in China. Here, we evaluate the completeness and transparency of RCT reports in this field. Methods: The following databases were searched: Medline, EMbase, SCI Expanded, China National Knowledge Infrastructure, the Chinese Biological Medicine Database, VIP database and Wan Fang databases) to search RCT reports on the effect comparison of laparoscopic surgery and open surgery for colorectal cancer in China. Our study evaluated the reporting quality of RCTs based on 22 standards of Consolidated Standards for Reporting Trials (CONSORT) 2010 Statement. Two reviewers responded with ‘yes’ or ‘no’ to each standard to judge whether the authors had reported or had recorded concrete details of the reports accomplished in accordance with the requirement of each standard. Results: A total of 40 relevant RCTs were included in the final analysis. For the ‘Title and abstract’, only three articles (7.5%) could be identified directly from its title as the report of RCTs. For the ‘Methods’, only three articles (7.5%) applied the method of random allocation of sequences; only two articles (5%) mentioned the type of randomization or gave the description of the mechanism of allocation concealment; no article referred the concrete implementation of random method. Only one article (2.5%) applied the method of blinding or sample size calculation; no article had analysis about the metaphase of an experiment or an explanation of its interruption. For ‘results’, only one article (2.5%) described participant flow, primary and secondary outcomes with estimated effect size or ancillary analyses. Only 13 articles (32.5%) showed baseline demographic and clinical characteristics, 10 (25%) referred to intention-to-treat analysis, and 12 (30%) mentioned important harms or unintended effects. For the ‘discussion’, only eight articles (20%) gave the description of trials’ limitations and 13 (32.5%) presented the generalizability (external validity, applicability) of the trial findings. Conclusion: The quality of the RCT reports on effect comparison of laparoscopic surgery and open surgery for colorectal cancer in China is poor. The reporting of RCTs in this field should be standardized, according to the specifications of the CONSORT 2010.

Is the relationship among outcome variables shown in randomized trials?

BackgroundRandomized controlled trials (RCTs) often have more than one primary outcome and frequently have secondary and harm outcomes. Comparison of outcomes between study arms is the primary focus of RCTs, but there are times when the relation between outcomes is important, such as determining whether an intermediate outcome and a clinical outcome have a strong association. We sought to determine how often reports of RCTs depict the relations among outcomes at the individual patient level and, for those studies that use composite outcomes, how often the relations between component elements are depicted.MethodsWe selected 20 general, specialty and subspecialty medical journals with high impact factors that publish original clinical research. We identified every RCT in the 2011 and 2012 issues and randomly selected 10 articles per journal. For each article we recorded the number of outcomes, the number of composite outcomes and how often the relations between outcomes or elements of composite outcomes were portrayed.ResultsAll but 16 of the 200 RCTs had more than one outcome. Thus, outcomes could have been related in 92% of studies, but such relations were only reported in 2 (1%). A total of 33 (17%) investigations measured a composite outcome, 32 of which showed data for each component. None, however, showed cross-tabulation of the components.ConclusionsReaders are rarely shown the relation between outcomes. Mandatory posting of datasets or requirements for detailed appendices would allow readers to see these cross-tabulations, helping future investigators know which outcomes are redundant, which provide unique information and which are most responsive to changes in the independent variables. While not every relationship between outcomes requires depiction, at present such information is seldom portrayed.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0584-6) contains supplementary material, which is available to authorized users.

Reporting of pre-enrolment screening with randomized clinical trials: A small item that could impact a big difference.

Introduction:Randomized controlled trials (RCTs), when conducted using ethical and transparent methods, become the ultimate standard for producing evidence-based knowledge in the field of medical research. We sought to determine the proportion of RCTs in which the number of screened patients is reported, and also to ascertain what predicted efficient screening (i.e., a high number of screened participants being enrolled).Materials and Methods:Thirty-five RCTs from the Journals Clinical Infectious Diseases and The Lancet Infectious Diseases were reviewed from the time period of January 2012 to July 2013 using standardised criteria.Results:From the 35 RCTs, 9 of 35 (26%) did not report the number of patients screened prior to recruitment. From the 26 studies that reported this screening figure, 10,215 (47%; range: 2-98%) of the screened participants (21,862) were subsequently enrolled. About 18.3% of those screened and not enrolled, met inclusion and exclusion criteria yet did not wish to participate in an RCT. Studies performed in developed countries and pediatric populations were more likely to have low rates of enrolment compared with the screened population although there was no statistical significance to these associations (P = 0.2 for both variables).Conclusion:Many reports of RCTs do not report screening figures, even though these add useful information about the feasibility of future trials.

Impact of adding a limitations section to abstracts of systematic reviews on readers' interpretation: a randomized controlled trial.

BackgroundTo allow an accurate evaluation of abstracts of systematic reviews, the PRISMA Statement recommends that the limitations of the evidence (e.g., risk of bias, publication bias, inconsistency, imprecision) should be described in the abstract. We aimed to evaluate the impact of adding such limitations sections on reader’s interpretation.MethodWe performed a two-arm parallel group randomized controlled trial (RCT) using a sample of 30 abstracts of systematic reviews evaluating the effects of healthcare intervention with conclusions favoring the beneficial effect of the experimental treatments. Two formats of these abstracts were derived: one reported without and one with a standardized limitations section written according to the PRISMA statement for abstracts. The primary outcome was readers’ confidence in the results of the systematic review as stated in the abstract assessed by a Likert scale from 0, not at all confident, to 10, very confident. In total, 300 participants (corresponding authors of RCT reports indexed in PubMed) were randomized by a web-based randomization procedure to interpret one abstract with a limitations section (n = 150) or without a limitations section (n = 150). Participants were blinded to the study hypothesis.ResultsAdding a limitations section did not modify readers’ interpretation of findings in terms of confidence in the results (mean difference [95% confidence interval] 0.19 [−0.37–0.74], p = 0.50), confidence in the validity of the conclusions (0.07 [−0.49–0.62], p = 0.80), or benefit of the experimental intervention (0.12 [−0.42–0.44], p = 0.65).This study is limited because the participants were expert-readers and are not representative of all systematic review readers.ConclusionAdding a limitations section to abstracts of systematic reviews did not affect readers’ interpretation of the abstract results. Other studies are needed to confirm the results and explore the impact of a limitations section on a less expert panel of participants.Trial registrationClinicalTrial.gov (NCT01848782).Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2288-14-123) contains supplementary material, which is available to authorized users.

Assessment of the reporting quality of ophthalmic diseases related randomized controlled trials published in SCI journals from mainland China

Background Randomized controlled trial (RCT) can offer high quality of evidence for the medical decisions.Consolidated standards of reporting trials (CONSORT) statement,an international criteria for RCT report,is a guideline and methodology of RCT report.However,the assessment and application of RCT according to CONSORT are dissatisfactory in China.Objective This study was to evaluate the reporting quality of ophthalmic diseases related RCTs published in SCI journals from mainland China and offer a good methodology of RCT report.Methods The RCT literature were searched on PubMed database according to Ophthalmology, Eye and all of their inferior subjective terms,and the published papers were limited in mainland China and before March,2013.Included papers were evaluated independently and checked by two searchers.The methodology and results of all retrieved papers were stratifiedly analyzed by the year of CONSORT published and revised.Results Sixty eligible RCTs were assessed,and the intervention methods were primarily surgery trials (34/60).Forty-four papers presented the comparison study of two groups with the median sample size of 76.0.Only 22％ (13/60) trial reports gave the clear identification of RCT in the title.Majority of papers described trial design,eligibility criteria for participants,detail of interventions and outcome measures.Twelve pieces of articles reported how sample size was determined,and 41 pieces referred settings and locations,but only 6 pieces recorded interim analyses and stopping guidelines.After CONSORT 2010 Statement was published,the proportion of trial reports that included details of the randomization had little improvement (RR=1.06,95％ CI:0.62-1.82).Only 42％ trial reports (25/60) offered a description about blinding method.Conclusions RCT reports related to ophthalmic diseases from mainland China in SCI journals are still flawed with certain shortcomings.Following the guidance of the CONSORT statement can improve the quality of ophthalmic diseases related RCT from mainland China. Key words: Consolidated standards of reporting trials; Publication; Randomized controlled trial; Ophthalmology; SCI journal; China

Consolidated Standards of Reporting Trials의 소개: 무작위 대조군 연구의 보고 지침

세계 유수의 의학관련 연구 저널의 편집자들은 제출된 원고의 질을 관리하기 위하여 연구진행의 가이드라인 역할을 할 수 있는 보고 지침을 개발하여 평가에 적용하고 있다. 따라서 본 연구는 RCTs를 위한 보고 지침인 CONSORT의 2010년 개정판 내용과 특징을 소개함으로써 치위생 연구의 계획 및 수행에 도움을 주고 더 나아가 EBP의 활성화에 기여하고자 하였다. CONSORT는 시험 보고의 질을 향상시킬 수 있도록 논문 저자들에게 보고 지침을 제공한다. 이 보고 지침은 RCTs 보고서에 반드시 포함되어야 할 필수 항목인 25개의 체크 리스트와 연구 과정의 도식화를 위한 순서도를 제시한다. 저자들은 연구 설계 시점부터 CONSORT의 각 항목을 참고함으로써 연구의 질을 향상시킬 수 있다. 따라서 우리 치위생계에서도 이러한 보고지침을 준수함으로써 치위생 연구의 타당성을 높이고, 이러한 연구 결과를 질 높은 근거 기반적 치위생 실무로 접목시켜 발전시킬 수 있을 것으로 생각된다. Recently, there are lots methodologies to improve the quality of research in medical and public health fields. One of them is to checking a process of research with a reporting guideline before reporting paper. Especially, reporting guideline for randomized controlled trials (RCTs) is the consolidated standards of reporting trials (CONSORT). Therefore, this review describes the latest version of the CONSORT statement, CONSORT 2010, including intent, background, and contents of this. The CONSORT statement comprises a checklist of essential items that should be included in reports of RCTs and a diagram for documenting the flow of participants through a trial. This report guideline aims at providing guidance to authors about how to improve the reporting of their trials. As consulting the CONSORT, authors could be strictly reported about research methods and results. From this review, we expect to elevate the quality of such research about dental hygiene and to establish the foundation for evidence-based dental hygiene.

Antigen-specific active immunotherapy for ovarian cancer.

Despite advances in chemotherapy, prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce tumour-antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. To assess the feasibility of antigen-specific active immunotherapy for ovarian cancer. Primary outcomes are clinical efficacy and antigen-specific immunogenicity with carrier-specific immunogenicity and side effects as secondary outcomes. For the previous version of this review, a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL) 2009, Issue 3, Cochrane Gynaecological Cancer Group Specialized Register, MEDLINE and EMBASE databases and clinicaltrials.gov was performed (1966 to July 2009). We conducted handsearches of the proceedings of relevant annual meetings (1996 to July 2009).For this update of the review the searches were extended to October 2013. Randomised controlled trials (RCTs), as well as non-randomised non-controlled studies that included participants with epithelial ovarian cancer, irrespective of stage of disease, and treated with antigen-specific active immunotherapy, irrespective of type of vaccine, antigen used, adjuvant used, route of vaccination, schedule, and reported clinical or immunological outcomes. Two reviews authors independently performed the data extraction. Risk of bias was evaluated for RCTs according to standard methodological procedures expected by The Cochrane Collabororation or for non-RCTs using a selection of quality domains deemed best applicable to the non-randomised non-controlled studies. Fifty-five studies were included (representing 3051 women with epithelial ovarian cancer). Response definitions showed substantial variation between trials, which makes comparison of trial results unreliable. Information on adverse events was frequently limited. Furthermore, reports of both RCTs and non-RCTs frequently lacked the relevant information necessary to assess risk of bias. Serious biases in most of the included trials can therefore not be ruled out.The largest body of evidence is currently available for CA-125 targeted antibody therapy (16 studies: 2339 participants). Non-RCTs of CA-125 targeted antibody therapy suggests increased survival in humoral and/or cellular responders. However, four large randomised placebo-controlled trials did not show any clinical benefit despite induction of immune responses in approximately 60% of participants.Other small studies targeting many different tumour antigens showed promising immunological results. As these strategies have not yet been tested in RCTs, no reliable inferences about clinical efficacy can be made. Given the promising immunological results, limited side effects and toxicity exploration of clinical efficacy in large well-designed RCTs may be worthwhile. We conclude that despite promising immunological responses, no clinically effective antigen-specific active immunotherapy is yet available for ovarian cancer. Results should be interpreted cautiously as there was a significant lack of relevant information for the assessment of risk of bias in both RCTs and non-RCTs.

Innovative approaches to clinical data management in resource limited settings using open-source technologies.

The primary objective of clinical datamanagement (CDM) is to provide high-quality, reliable data for reporting ran-domized controlled trials (RCTs) in linewith good clinical practice (GCP) require-ments. For treatment trials of neglectedtropical diseases (NTDs) in endemic coun-tries, CDM systems need to be efficientand affordable. Challenges include poorinfrastructure, license costs associated withGCP-compliant software, and limitedhuman resources to provide the requiredexpertise. We argue that high-qualityCDM for NTDs can be achieved and thatchallenges can be overcome through theuse of readily available open-access tools.The Drugs for Neglected Diseasesinitiative (DNDi) [1,2] sponsors severalRCTs of treatments for visceral leishman-iasis (VL) in eastern Africa, working withregional partners through the Leishmani-asis East Africa Platform (LEAP). Thesetrials are conducted according to GCPstandards to ensure internal and externalvalidity, with CDM conducted by theauthors at the Data Centre (DC) basedat DNDi Africa in Nairobi.Choice of proprietary or open-sourcetools is dependent largely on budget anduser experience, with tools used indepen-dently or in combination. We have beenworking to overcome two main challenges:(1) Telecommunication, in particularwith unstable internet connectivity.An ideal tool for CDM would allowimplementation with or without aninternet connection (online and offlinemodes respectively) and be configuredfor use across multiple remote sites.(2) Automated query generation andresolution to provide an audit trailensuring consistency, rigor, and limit-ed risk of human error.We describe our development of two newtools for CDM: an offline module forOpenClinicausersandaquerymanagementsystem (QMS) that allows automation andstandardization of query management withmultiple-user access.

Low Adequacy Between Severe Adverse Events Reporting in Oncology Phase III Trials and Expectations of the Eortc Members

ABSTRACT Aim: Reports of randomized controlled trials (RCTs) published in oncology literature are generally poorly conform to the 2004 Consolidated Standards of Reporting Trials (CONSORT ) extension for harms. We assessed the consistency in between expectations of a panel of EORTC experts regarding reporting of AEs and the actual quality of publication of RCTs. Methods: Reporting of severe-AEs, AEs related outcomes and composite AEs outcomes were reviewed in 325 oncology RCTs reports published between 2007 and 2011. An online survey was sent to the network of EORTC investigators to evaluate their expectation concerning the AE reporting. Then we compared AE reporting in phase III reports with EORTC member expectations. The characteristics of the article associated with better quality in AEs related outcomes reporting were also investigated. Results: A total of 211 EORTC members have responded to the survey. Among them, 99% thought that all lethal AEs (LAEs) should be reported and 95% thought that all AE leading to withdrawal should also be reported. Clearly described LAEs were found in 190 out of 325 RCTs (58%) and AEs leading to withdrawal were correctly reported in 53 out of 325 RCTs (16%). LAEs were more correctly reported in North-America / Intercontinental trials (p = 0.0004) and in trials testing a molecular targeted therapy (p = 0.016). AEs leading to withdrawals were more correctly reported in RCTs funded by industry (p = 0,001). Composite AEs such as “dermatologic AEs” or “neurologic AEs” were used in 95 out of 325 RCTs (29%); 25% of them were clearly described. Conclusions: There are important discrepancies between the expectations of EORTC network investigators and the reporting quality of AE reporting in oncology phase III reports. Recommendations able to improve the reporting of severe-AE reporting in oncology phase III reports are discussed. Disclosure: All authors have declared no conflicts of interest.

Realities of observational study registration.

Interest in registration of observational studies is growing. Observational studies (OSs)3 of human subjects represent a large fraction of published scientific reports and may be considered closer to bedside than clinical trials (CTs), yet the majority are unregistered in prospective study registries. A recent article by Dal-Re et al. in Science Translational Medicine (1) provides commentary on the ethical and scientific rationale supporting prospective registration of OSs. To briefly illustrate their point, the authors performed a literature search of PubMed articles from 2011 and observed that the number of publications from OSs outnumbered those from randomized controlled trials (RCTs) almost 300 000 to 20 000. Although approximately 20% of RCT reports were accompanied by a registration number, the registration of OSs was …

Continuous passive motion for preventing venous thromboembolism after total knee arthroplasty.

Total knee arthroplasty (TKA) is a common form of orthopaedic surgery. Venous thromboembolism (VTE), which consists of deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major and potentially fatal complication after TKA. The incidence of DVT after TKA is 40% to 80% and the incidence of PE is approximately 2%. It is generally agreed that thromboprophylaxis should be used in patients who undergo TKA. Both pharmacological and mechanical methods are used in the prevention of DVT. Pharmacological methods alter the blood coagulation profile and may increase the risk of bleeding complications. When pharmacological methods cannot be used the mechanical methods become crucial for VTE prophylaxis. Continuous passive motion (CPM) is provided through an external motorised device which enables a joint to move passively throughout a preset arc of motion. Despite the theoretical effectiveness and widespread use of CPM, there are still differing views on the effectiveness of CPM as prophylaxis against thrombosis after TKA. This is an update of the review first published in 2012. The aim of this review was to determine the effectiveness of continuous passive motion (CPM) therapy for preventing venous thromboembolism (VTE) in patients after total knee arthroplasty (TKA). For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014), CENTRAL (2014, Issue 1), Ovid MEDLINE (to week 1 February 2014) and EMBASE (to Week 07 2014). Randomised controlled trials (RCTs) comparing the use of CPM with control in preventing DVT or PE after TKA. People aged 18 years and older who had undergone TKA were included in this review. We excluded studies of patients who presented with DVT at baseline. The experimental and control groups received similar postoperative care and therapy other than the CPM. Two review authors independently assessed the citations retrieved by the search strategies for reports of relevant RCTs. They independently selected trials that satisfied the inclusion criteria, extracted data and undertook quality assessment. Effects were estimated as risk ratios (RRs), mean differences or standardised mean differences with 95% confidence intervals (CIs). Meta-analyses were performed using a fixed-effect model for continuous variables. Where heterogeneity existed (determined by the I(2) statistic) a random-effects model was used. Eleven RCTs involving 808 participants met the inclusion criteria. The methodological quality of the included studies was variable and most of the predefined outcomes were reported by only one or two studies, therefore the quality of the evidence was low. Five studies with a total of 405 patients reported the incidence of DVT. In the CPM group (205 patients) 36 developed DVT (18%) compared to 29 (15%) in the control group (200 patients). The results of the meta-analysis showed no evidence that CPM had any effect on preventing VTE after TKA (RR 1.22, 95% CI 0.84 to 1.79). One trial (150 participants) did not find PE in any of the patients during hospitalisation or in the subsequent three months. PE was not reported in the other included studies. None of the trials reported deaths among the included participants. There is not enough evidence from the available RCTs to conclude that CPM reduces VTE after TKA. We cannot assess the effect of CPM on mortality because no such events occurred amongst the participants of these trials. The quality of the evidence was low. The results are supported by only a small number of studies, most of which are of low to moderate quality.

Randomized controlled trials and challenge trials: design and criterion for validity.

This article is the third of six articles addressing systematic reviews in animal agriculture and veterinary medicine. This article provides an overview of clinical trials, both randomized controlled trials (RCTs) and challenge trials, where the disease outcome is deliberately induced by the investigator. RCTs are not the only study design used in systematic reviews, but are preferred when available as the gold standard for evaluating interventions under real-world conditions. RCTs are planned experiments, which involve diseased or at-risk study subjects and are designed to evaluate interventions (therapeutic treatments or preventive strategies, including antibiotics, vaccines, management practices, dietary changes, management changes or lifestyle changes). Key components of the RCT are the use of one or more comparison (control) groups and investigator control over intervention allocation. Important design features in RCTs include as follows: how the population is selected, approach to allocation of intervention and control group subjects, how allocation is concealed prior to enrolment of study subjects, how outcomes are defined, how allocation to group is concealed (blinding) and how withdrawals from the study are managed. Guidelines for reporting important features of RCTs have been published and are useful tools for writing, reviewing and reading reports of RCTs.

A meta-analysis of randomized trials of telmisartan versus active controls for insulin resistance in hypertensive patients

To determine whether telmisartan improves insulin resistance compared with other antihypertensive drugs, we performed a meta-analysis of randomized controlled trials (RCTs) of telmisartan. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through December 2013. Eligible studies were prospective RCTs of telmisartan versus other antihypertensive drugs, enrolling individuals with hypertension and reporting insulin levels and/or homeostasis model assessment-insulin resistance (HOMA-IR) as outcomes. Of 67 potentially relevant articles screened initially, 33 reports of RCTs enrolling a total of 2033 patients with hypertension were identified and included. Pooled analyses of only the eight double-blind-design trials demonstrated statistically significant reductions in percent changes of insulin levels (mean difference, −5.19%; 95% confidence interval, −8.94% to −1.43%; P = .007) and HOMA-IR (−15.34%; −26.39% to −4.28%; P = .007) with telmisartan relative to other antihypertensive drugs. When data from all the 33 trials were pooled, telmisartan was associated with statistically significant reductions in percent changes of insulin levels (−10.92%; −15.60% to −6.23%; P < .00001) and HOMA-IR (−15.89%; −22.01% to −9.78%; P < .00001) relative to other antihypertensive drugs. In conclusion, telmisartan appears to significantly improve insulin resistance compared with other antihypertensive drugs in patients with hypertension.

Type II error and statistical power in reports of small animal clinical trials.

To describe reporting of key methodological elements associated with type II error in published reports of small animal randomized controlled trials (RCTs) and to determine the statistical power in a subset of RCTs with negative results. Descriptive literature survey. Reports of parallel-group clinical RCTs published in 11 English-language veterinary journals from 2005 to 2012. Predefined criteria were used to identify trial primary outcomes and classify results as negative or positive. Details of sample size determination and use of confidence intervals in results reporting were recorded. For each 2-group RCT with negative results, the statistical power to detect 25% and 50% relative differences in outcome was calculated. Of 238 RCTs, 42 (18%) stated a primary outcome, 52 (22%) reported a sample size calculation, and 18 (9%) included a confidence interval around the observed treatment effect. Reports of only 2 (0.8%) RCTs included all 3 elements. Among 103 two-group RCTs with negative results, only 14 (14%) and 40 (39%) were sufficiently powered (β < 0.20) to detect 25% and 50% relative differences in outcome between treatments, respectively. The present survey found that small animal RCTs with negative results were often underpowered to detect moderate-to-large effect sizes between study groups. Information needed for critical appraisal was missing from most reports. The potential for clinicians to base treatment decisions on inappropriate interpretations of RCTs was worrisome. Design and reporting of small animal RCTs must be improved.

Methodological reporting quality of randomized controlled trials in three spine journals from 2010 to 2012.

To elucidate the methodological reporting quality of randomized controlled trials (RCTs) in three spine journals from 2010 to 2012. In this study, we summarized the methodological report of RCTs in three major spine journals, including the Spine Journal, Spine and the European Spine Journal from 2010 to 2012. The methodological reporting quality, including the allocation sequence generation, allocation concealment, blinding and sample size calculation, was revealed. Number of patients, funding source, type of intervention and country were also retrieved from each trial. The methodological reporting quality was descriptively reported. Ninety trials were involved and 57.8% (52/90) reported adequate allocation sequence generation, 46.7% (42/90) reported adequate allocation concealment, 34.4% (31/90) reported adequate blinding and 37.8% (34/90) reported adequate sample size calculation. This study shows that the methodological reporting quality of RCTs in the spine field needs further improvement.