[Methodological quality evaluation of randomized controlled trials for traditional Chinese medicines for treatment of sub-health].

Science.gov (United States)

Zhao, Jun; Liao, Xing; Zhao, Hui; Li, Zhi-Geng; Wang, Nan-Yue; Wang, Li-Min

2016-11-01

To evaluate the methodological quality of the randomized controlled trials(RCTs) for traditional Chinese medicines for treatment of sub-health, in order to provide a scientific basis for the improvement of clinical trials and systematic review. Such databases as CNKI, CBM, VIP, Wanfang, EMbase, Medline, Clinical Trials, Web of Science and Cochrane Library were searched for RCTS for traditional Chinese medicines for treatment of sub-health between the time of establishment and February 29, 2016. Cochrane Handbook 5.1 was used to screen literatures and extract data, and CONSORT statement and CONSORT for traditional Chinese medicine statement were adopted as the basis for quality evaluation. Among the 72 RCTs included in this study, 67 (93.05%) trials described the inter-group baseline data comparability, 39(54.17%) trials described the unified diagnostic criteria, 28(38.89%) trials described the unified standards of efficacy, 4 (5.55%) trials mentioned the multi-center study, 19(26.38%) trials disclosed the random distribution method, 6(8.33%) trials used the random distribution concealment, 15(20.83%) trials adopted the method of blindness, 3(4.17%) study reported the sample size estimation in details, 5 (6.94%) trials showed a sample size of more than two hundred, 19(26.38%) trials reported the number of withdrawal, defluxion cases and those lost to follow-up, but only 2 trials adopted the ITT analysis,10(13.89%) trials reported the follow-up results, none of the trial reported the test registration and the test protocol, 48(66.7%) trials reported all of the indicators of expected outcomes, 26(36.11%) trials reported the adverse reactions and adverse events, and 4(5.56%) trials reported patient compliance. The overall quality of these randomized controlled trials for traditional Chinese medicines for treatment of sub-health is low, with methodological defects in different degrees. Therefore, it is still necessary to emphasize the correct application of principles

Adherence of randomized trials within children's surgical specialties published during 2000 to 2009 to standard reporting guidelines.

Science.gov (United States)

Blakely, Martin L; Kao, Lillian S; Tsao, Kuojen; Huang, Eunice Y; Tsai, Anthony; Tanaka, Stacy; Younas, Shiraz; Lu, Zengqi; Lally, Kevin P

2013-09-01

Randomized clinical trials (RCTs) are uncommon in pediatric surgical specialties and the quality of reporting is unknown. Our primary purpose was to analyze published surgical RCTs involving children to measure adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Published RCTs from January 1, 2000 through December 31, 2009 were reviewed. The trials were evaluated for the presence of 7 CONSORT guidelines and also graded according to the Jadad scale. Two hundred and twenty-eight trials were included. Five trials met all 7 CONSORT criteria (2%) and 53 had a Jadad score of ≥3 (23%). Slightly more than 50% of all trials specified primary outcomes and guidelines for allocation concealment, randomization description, and attrition details was even lower. There were significant differences between surgical specialties with regard to CONSORT adherence to the majority of the guidelines. Pediatric general surgery had the largest number of published RCTs. Pediatric orthopaedic surgery had the highest proportion of trials with a Jadad score ≥3 (40%). Adherence to CONSORT guidelines is low across the spectrum of children's surgical specialties, although significant differences do exist. Future RCTs in children's surgical specialties should specifically focus on areas of low adherence to reporting guidelines. Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

A review of dipeptidyl peptidase-4 inhibitors. Hot topics from randomized controlled trials

DEFF Research Database (Denmark)

Deacon, Carolyn F

2018-01-01

The first clinical study to investigate effects of dipeptidyl peptidase-4 (DPP-4) inhibition was published in 2002, and since then, numerous randomized controlled trials (RCTs) have shown that DPP-4 inhibitors are efficacious, safe and well-tolerated. This review will focus upon RCTs which have i...

Quality of Reporting of Randomized Clinical Trials in Tai Chi Interventions—A Systematic Review

Directory of Open Access Journals (Sweden)

Jing-Yi Li

2011-01-01

Full Text Available Objectives. To evaluate the reporting quality of published randomized clinical trials (RCTs in the Tai Chi literature following the publication of the CONSORT guidelines in 2001. Data Sources. The OVID MEDLINE and PUBMED databases. Review Methods. To survey the general characteristics of Tai Chi RCTs in the literature, we included any report if (i it was an original report of the trial; (ii its design was RCT; (iii one of the treatments being tested was Tai Chi; and (iv it was in English. In addition, we assessed the reporting quality of RCTs that were published between 2002 and 2007, using a modified CONSORT checklist of 40 items. The adequate description of Tai Chi interventions in these trials was examined against a 10-item checklist adapted from previous reviews. Results. The search yielded 31 Tai Chi RCTs published from 2002 to 2007 and only 11 for 1992–2001. Among trials published during 2002–2007, the most adequately reported criteria were related to background, participant eligibility and interpretation of the study results. Nonetheless, the most poorly reported items were associated with randomization allocation concealment, implementation of randomization and the definitions of period of recruitment and follow-up. In addition, only 23% of RCTs provided adequate details of Tai Chi intervention used in the trials. Conclusion. The findings in this review indicated that the reporting quality of Tai Chi intervention trials is sub-optimal. Substantial improvement is required to meet the CONSORT guidelines and allow assessment of the quality of evidence. We believe that not only investigators, but also journal editors, reviewers and funding agencies need to follow the CONSORT guidelines to improve the standards of research and strengthen the evidence base for Tai Chi and for complementary and alternative medicine.

The Risk of Bias in Randomized Trials in General Dentistry Journals.

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Hinton, Stephanie; Beyari, Mohammed M; Madden, Kim; Lamfon, Hanadi A

2015-01-01

The use of a randomized controlled trial (RCT) research design is considered the gold standard for conducting evidence-based clinical research. In this present study, we aimed to assess the quality of RCTs in dentistry and create a general foundation for evidence-based dentistry on which to perform subsequent RCTs. We conducted a systematic assessment of bias of RCTs in seven general dentistry journals published between January 2011 and March 2012. We extracted study characteristics in duplicate and assessed each trial's quality using the Cochrane Risk of Bias tool. We compared risk of bias across studies graphically. Among 1,755 studies across seven journals, we identified 67 RCTs. Many included studies were conducted in Europe (39%), with an average sample size of 358 participants. These studies included 52% female participants and the maximum follow-up period was 13 years. Overall, we found a high percentage of unclear risk of bias among included RCTs, indicating poor quality of reporting within the included studies. An overall high proportion of trials with an "unclear risk of bias" suggests the need for better quality of reporting in dentistry. As such, key concepts in dental research and future trials should focus on high-quality reporting.

Trends in 'poor responder' research: lessons learned from RCTs in assisted conception.

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Papathanasiou, Athanasios; Searle, Belinda J; King, Nicole M A; Bhattacharya, Siladitya

2016-04-01

A substantial minority of women undergoing IVF will under-respond to controlled ovarian hyperstimulation. These women-so-called 'poor responders'-suffer persistently reduced success rates after IVF. Currently, no single intervention is unanimously accepted as beneficial in overcoming poor ovarian response (POR). This has been supported by the available research on POR, which consists mainly of randomized controlled trials (RCTs ) with an inherent high-risk of bias. The aim of this review was to critically appraise the available experimental trials on POR and provide guidance towards more useful-less wasteful-future research. A comprehensive review was undertaken of RCTs on 'poor responders' published in the last 15 years. Data on various methodological traits as well as important clinical characteristics were extracted from the included studies and summarized, with a view to identifying deficiencies from which lessons can be learned. Based on this analysis, recommendations were provided for further research in this field of assisted conception. We selected and analysed 75 RCTs. A valid, 'low-risk' randomization method was reported in three out of four RCTs. An improving trend in reporting concealment of patient allocation was also evident over the 15-year period. In contrast, methodological quality were more likely to have been published in a high-impact journal. Overall, the majority of published trials on POR suffer from methodological flaws and are, thus, regarded as being high-risk for bias. The same trials have used a variety of definitions for their poor responders and a variety of interventions for their head-to-head comparisons. Not surprisingly, discrepancies are also evident in the findings of trials comparing similar interventions. Based on the identified deficiencies, this novel type of 'methodology and clinical' review has introduced custom recommendations on how to improve future experimental research in the 'poor responder' population. © The Author

Revisiting the Quality of Reporting Randomized Controlled Trials in Nursing Literature.

Science.gov (United States)

Adams, Yenupini Joyce; Kamp, Kendra; Liu, Cheng Ching; Stommel, Manfred; Thana, Kanjana; Broome, Marion E; Smith, Barbara

2018-03-01

To examine and update the literature on the quality of randomized controlled trials (RCTs) as reported in top nursing journals, based on manuscripts' adherence to the CONsolidated Standards of Reporting Trials (CONSORT) guidelines. Descriptive review of adherence of RCT manuscript to CONSORT guidelines. Top 40 International Scientific Indexing (ISI) ranked nursing journals that published 20 or more RCTs between 2010 and 2014, were included in the study. Selected articles were randomly assigned to four reviewers who assessed the quality of the articles using the CONSORT checklist. Data were analyzed using descriptive and inferential statistics. A total of 119 articles were included in the review. The mean CONSORT score significantly differed by journal but did not differ based on year of publication. The least consistently reported items included random allocation, who randomly assigned participants and whether those administering the interventions were blinded to group assignment. Although progress has been made, there is still room for improvement in the quality of RCT reporting in nursing journals. Special attention must be paid to how adequately studies adhere to the CONSORT prior to publication in nursing journals. Evidence from (RCTs) are thought to provide the best evidence for evaluating the impact of treatments and interventions by the U.S. Preventive Services Task Force. Since the evidence may be used for the development of clinical practice guidelines, it is critical that RCTs be designed, conducted, and reported appropriately and precisely. © 2017 Sigma Theta Tau International.

Comparison of Registered and Reported Outcomes in Randomized Clinical Trials Published in Anesthesiology Journals.

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Jones, Philip M; Chow, Jeffrey T Y; Arango, Miguel F; Fridfinnson, Jason A; Gai, Nan; Lam, Kevin; Turkstra, Timothy P

2017-10-01

Randomized clinical trials (RCTs) provide high-quality evidence for clinical decision-making. Trial registration is one of the many tools used to improve the reporting of RCTs by reducing publication bias and selective outcome reporting bias. The purpose of our study is to examine whether RCTs published in the top 6 general anesthesiology journals were adequately registered and whether the reported primary and secondary outcomes corresponded to the originally registered outcomes. Following a prespecified protocol, an electronic database was used to systematically screen and extract data from RCTs published in the top 6 general anesthesiology journals by impact factor (Anaesthesia, Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of Anesthesia, and European Journal of Anaesthesiology) during the years 2007, 2010, 2013, and 2015. A manual search of each journal's Table of Contents was performed (in duplicate) to identify eligible RCTs. An adequately registered trial was defined as being registered in a publicly available trials registry before the first patient being enrolled with an unambiguously defined primary outcome. For adequately registered trials, the outcomes registered in the trial registry were compared with the outcomes reported in the article, with outcome discrepancies documented and analyzed by the type of discrepancy. During the 4 years studied, there were 860 RCTs identified, with 102 RCTs determined to be adequately registered (12%). The proportion of adequately registered trials increased over time, with 38% of RCTs being adequately registered in 2015. The most common reason in 2015 for inadequate registration was registering the RCT after the first patient had already been enrolled. Among adequately registered trials, 92% had at least 1 primary or secondary outcome discrepancy. In 2015, 42% of RCTs had at least 1 primary outcome discrepancy, while 90% of RCTs had at least 1 secondary outcome discrepancy

Synthesis of results of randomized controlled trials of contrast media

International Nuclear Information System (INIS)

Kinnison, M.L.; Powe, N.R.; Steinberg, E.P.

1988-01-01

The authors review 100 randomized controlled trials (RCTs) that examine the safety or efficacy of new low-osmolality contrast media (LOM) and focus on the 43 RCTs judged to be of the highest quality. These RCTs showed no consistent differences in nephrotoxicity between high- and low-osmolality contrast media. Certain cardiovascular parameters were altered less with low-osmolality agents during intracardiac injection, but the clinical significance of these differences in unclear. Heat and pain sensations occurred less often with low-osmolality contrast media. No differences were noted in the incidence of nausea, vomiting, urticaria, or bronchospasm. Even with numerous RCTs comparing these media, physicians still must make economically significant choices about contrast media without sufficient data about their relative safety

Moxibustion for the treatment of chemotherapy-induced leukopenia: a systematic review of randomized clinical trials.

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Choi, Tae-Young; Lee, Myeong Soo; Ernst, Edzard

2015-06-01

The purpose of this study is to assess the efficacy of moxibustion as a treatment of chemotherapy-induced leukopenia. Twelve databases were searched from their inception through June 2014, without a language restriction. Randomized clinical trials (RCTs) were included if moxibustion was used as the sole treatment or as a part of a combination therapy with conventional drugs for leukopenia induced by chemotherapy. Cochrane criteria were used to assess the risk of bias. Six RCTs with a total of 681 patients met our inclusion criteria. All of the included RCTs were associated with a high risk of bias. The trials included patients with various types of cancer receiving ongoing chemotherapy or after chemotherapy. The results of two RCTs suggested the effectiveness of moxibustion combined with chemotherapy vs. chemotherapy alone. In four RCTs, moxibustion was more effective than conventional drug therapy. Six RCTs showed that moxibustion was more effective than various types of control interventions in increasing white blood cell counts. There is low level of evidence based on these six trials that demonstrates the superiority of moxibustion over drug therapies in the treatment of chemotherapy-induced leukopenia. However, the number of trials, the total sample size, and the methodological quality are too low to draw firm conclusions. Future RCTs appear to be warranted.

Network meta-analysis incorporating randomized controlled trials and non-randomized comparative cohort studies for assessing the safety and effectiveness of medical treatments: challenges and opportunities

OpenAIRE

Cameron, Chris; Fireman, Bruce; Hutton, Brian; Clifford, Tammy; Coyle, Doug; Wells, George; Dormuth, Colin R.; Platt, Robert; Toh, Sengwee

2015-01-01

Network meta-analysis is increasingly used to allow comparison of multiple treatment alternatives simultaneously, some of which may not have been compared directly in primary research studies. The majority of network meta-analyses published to date have incorporated data from randomized controlled trials (RCTs) only; however, inclusion of non-randomized studies may sometimes be considered. Non-randomized studies can complement RCTs or address some of their limitations, such as short follow-up...

Cost-efficiency of knowledge creation: randomized controlled trials vs. observational studies.

Science.gov (United States)

Struck, Rafael; Baumgarten, Georg; Wittmann, Maria

2014-04-01

This article reviews traditional and current perspectives on randomized, controlled trials (RCTs) and observational studies relative to the economic implications for public healthcare stakeholders. It takes an average of 17 years to bring 14% of original research into clinical practice. Results from high-quality observational studies may complement limited RCTs in primary and secondary literature bases, and enhance the incorporation of sound evidence-based guidelines. Observational findings from comprehensive medical databases may offer valuable clues on the effectiveness and relevance of public healthcare interventions. Major expenditures associated with RCTs relate to recruitment, inappropriate site selection, conduct and reporting. Application of business strategies and economic evaluation tools, in addition to the planning and conduct of RCTs, may enhance clinical trial site performances. Considering the strengths and limitations of each study type, clinical researchers should explore the contextual worthiness of either design in promulgating knowledge. They should focus on quality of conduct and reporting that may allow for the liberation of limited public and private clinical research funding.

The association of funding source on effect size in randomized controlled trials: 2013-2015 - a cross-sectional survey and meta-analysis.

Science.gov (United States)

Falk Delgado, Alberto; Falk Delgado, Anna

2017-03-14

Trials financed by for-profit organizations have been associated with favorable outcomes of new treatments, although the effect size of funding source impact on outcome is unknown. The aim of this study was to estimate the effect size for a favorable outcome in randomized controlled trials (RCTs), stratified by funding source, that have been published in general medical journals. Parallel-group RCTs published in The Lancet, New England Journal of Medicine, and JAMA between 2013 and 2015 were identified. RCTs with binary primary endpoints were included. The primary outcome was the OR of patients' having a favorable outcome in the intervention group compared with the control group. The OR of a favorable outcome in each trial was calculated by the number of positive events that occurred in the intervention and control groups. A meta-analytic technique with random effects model was used to calculate summary OR. Data were stratified by funding source as for-profit, mixed, and nonprofit. Prespecified sensitivity, subgroup, and metaregression analyses were performed. Five hundred nine trials were included. The OR for a favorable outcome in for-profit-funded RCTs was 1.92 (95% CI 1.72-2.14), which was higher than mixed source-funded RCTs (OR 1.34, 95% CI 1.25-1.43) and nonprofit-funded RCTs (OR 1.32, 95% CI 1.26-1.39). The OR for a favorable outcome was higher for both clinical and surrogate endpoints in for-profit-funded trials than in RCTs with other funding sources. Excluding drug trials lowered the OR for a favorable outcome in for-profit-funded RCTs. The OR for a favorable surrogate outcome in drug trials was higher in for-profit-funded trials than in nonprofit-funded trials. For-profit-funded RCTs have a higher OR for a favorable outcome than nonprofit- and mixed source-funded RCTs. This difference is associated mainly with the use of surrogate endpoints in for-profit-financed drug trials.

Randomized controlled trials of simulation-based interventions in Emergency Medicine: a methodological review.

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Chauvin, Anthony; Truchot, Jennifer; Bafeta, Aida; Pateron, Dominique; Plaisance, Patrick; Yordanov, Youri

2018-04-01

The number of trials assessing Simulation-Based Medical Education (SBME) interventions has rapidly expanded. Many studies show that potential flaws in design, conduct and reporting of randomized controlled trials (RCTs) can bias their results. We conducted a methodological review of RCTs assessing a SBME in Emergency Medicine (EM) and examined their methodological characteristics. We searched MEDLINE via PubMed for RCT that assessed a simulation intervention in EM, published in 6 general and internal medicine and in the top 10 EM journals. The Cochrane Collaboration risk of Bias tool was used to assess risk of bias, intervention reporting was evaluated based on the "template for intervention description and replication" checklist, and methodological quality was evaluated by the Medical Education Research Study Quality Instrument. Reports selection and data extraction was done by 2 independents researchers. From 1394 RCTs screened, 68 trials assessed a SBME intervention. They represent one quarter of our sample. Cardiopulmonary resuscitation (CPR) is the most frequent topic (81%). Random sequence generation and allocation concealment were performed correctly in 66 and 49% of trials. Blinding of participants and assessors was performed correctly in 19 and 68%. Risk of attrition bias was low in three-quarters of the studies (n = 51). Risk of selective reporting bias was unclear in nearly all studies. The mean MERQSI score was of 13.4/18.4% of the reports provided a description allowing the intervention replication. Trials assessing simulation represent one quarter of RCTs in EM. Their quality remains unclear, and reproducing the interventions appears challenging due to reporting issues.

Intervention randomized controlled trials involving wrist and shoulder arthroscopy: a systematic review

Science.gov (United States)

2014-01-01

Background Although arthroscopy of upper extremity joints was initially a diagnostic tool, it is increasingly used for therapeutic interventions. Randomized controlled trials (RCTs) are considered the gold standard for assessing treatment efficacy. We aimed to review the literature for intervention RCTs involving wrist and shoulder arthroscopy. Methods We performed a systematic review for RCTs in which at least one arm was an intervention performed through wrist arthroscopy or shoulder arthroscopy. PubMed and Cochrane Library databases were searched up to December 2012. Two researchers reviewed each article and recorded the condition treated, randomization method, number of randomized participants, time of randomization, outcomes measures, blinding, and description of dropouts and withdrawals. We used the modified Jadad scale that considers the randomization method, blinding, and dropouts/withdrawals; score 0 (lowest quality) to 5 (highest quality). The scores for the wrist and shoulder RCTs were compared with the Mann–Whitney test. Results The first references to both wrist and shoulder arthroscopy appeared in the late 1970s. The search found 4 wrist arthroscopy intervention RCTs (Kienböck’s disease, dorsal wrist ganglia, volar wrist ganglia, and distal radius fracture; first 3 compared arthroscopic with open surgery). The median number of participants was 45. The search found 50 shoulder arthroscopy intervention RCTs (rotator cuff tears 22, instability 14, impingement 9, and other conditions 5). Of these, 31 compared different arthroscopic treatments, 12 compared arthroscopic with open treatment, and 7 compared arthroscopic with nonoperative treatment. The median number of participants was 60. The median modified Jadad score for the wrist RCTs was 0.5 (range 0–1) and for the shoulder RCTs 3.0 (range 0–5) (p = 0.012). Conclusion Despite the increasing use of wrist arthroscopy in the treatment of various wrist disorders the efficacy of arthroscopically

Diagnosis checking of statistical analysis in RCTs indexed in PubMed.

Science.gov (United States)

Lee, Paul H; Tse, Andy C Y

2017-11-01

Statistical analysis is essential for reporting of the results of randomized controlled trials (RCTs), as well as evaluating their effectiveness. However, the validity of a statistical analysis also depends on whether the assumptions of that analysis are valid. To review all RCTs published in journals indexed in PubMed during December 2014 to provide a complete picture of how RCTs handle assumptions of statistical analysis. We reviewed all RCTs published in December 2014 that appeared in journals indexed in PubMed using the Cochrane highly sensitive search strategy. The 2014 impact factors of the journals were used as proxies for their quality. The type of statistical analysis used and whether the assumptions of the analysis were tested were reviewed. In total, 451 papers were included. Of the 278 papers that reported a crude analysis for the primary outcomes, 31 (27·2%) reported whether the outcome was normally distributed. Of the 172 papers that reported an adjusted analysis for the primary outcomes, diagnosis checking was rarely conducted, with only 20%, 8·6% and 7% checked for generalized linear model, Cox proportional hazard model and multilevel model, respectively. Study characteristics (study type, drug trial, funding sources, journal type and endorsement of CONSORT guidelines) were not associated with the reporting of diagnosis checking. The diagnosis of statistical analyses in RCTs published in PubMed-indexed journals was usually absent. Journals should provide guidelines about the reporting of a diagnosis of assumptions. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

Quality of methodological reporting of randomized clinical trials of sodium-glucose cotransporter-2 (sglt2 inhibitors

Directory of Open Access Journals (Sweden)

Hadeel Alfahmi

2017-01-01

Full Text Available Sodium-glucose cotransporter-2 (SGLT2 inhibitors are a new class of medicines approved recently for the treatment of type 2 diabetes. To improve the quality of randomized clinical trial (RCT reports, the Consolidated Standards of Reporting Trials (CONSORT statement for methodological features was created. For achieving our objective in this study, we assessed the quality of methodological reporting of RCTs of SGLT2 inhibitors according to the 2010 CONSORT statement. We reviewed and analyzed the methodology of SGLT2 inhibitors RCTs that were approved by the Food & Drug Administration (FDA. Of the 27 trials, participants, eligibility criteria, and additional analyses were reported in 100% of the trials. In addition, trial design, interventions, and statistical methods were reported in 96.3% of the trials. Outcomes were reported in 93.6% of the trials. Settings were reported in 85.2% of the trials. Blinding and sample size were reported in 66.7 and 59.3% of the trials, respectively. Sequence allocation and the type of randomization were reported in 63 and 74.1% of the trials, respectively. Besides those, a few methodological items were inadequate in the trials. Allocation concealment was inadequate in most of the trials. It was reported only in 11.1% of the trials. The majority of RCTs have high percentage adherence for more than half of the methodological items of the 2010 CONSORT statement.

A quantum-like model of homeopathy clinical trials: importance of in situ randomization and unblinding.

Science.gov (United States)

Beauvais, Francis

2013-04-01

The randomized controlled trial (RCT) is the 'gold standard' of modern clinical pharmacology. However, for many practitioners of homeopathy, blind RCTs are an inadequate research tool for testing complex therapies such as homeopathy. Classical probabilities used in biological sciences and in medicine are only a special case of the generalized theory of probability used in quantum physics. I describe homeopathy trials using a quantum-like statistical model, a model inspired by quantum physics and taking into consideration superposition of states, non-commuting observables, probability interferences, contextuality, etc. The negative effect of blinding on success of homeopathy trials and the 'smearing effect' ('specific' effects of homeopathy medicine occurring in the placebo group) are described by quantum-like probabilities without supplementary ad hoc hypotheses. The difference of positive outcome rates between placebo and homeopathy groups frequently vanish in centralized blind trials. The model proposed here suggests a way to circumvent such problems in masked homeopathy trials by incorporating in situ randomization/unblinding. In this quantum-like model of homeopathy clinical trials, success in open-label setting and failure with centralized blind RCTs emerge logically from the formalism. This model suggests that significant differences between placebo and homeopathy in blind RCTs would be found more frequently if in situ randomization/unblinding was used. Copyright © 2013. Published by Elsevier Ltd.

Structured triglyceride for parenteral nutrition: meta-analysis of randomized controlled trials.

Science.gov (United States)

Zhou, Yong; Wu, Xiao-Ting; Li, Ni; Zhuang, Wen; Liu, Guanjian; Wu, Taixiang; Wei, Mao-Ling

2006-01-01

This study assessed the safety and efficacy of structured triglyceride (ST) for parenteral nutrition. A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. Clinical trials were identified from the following electronic databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Chinese Bio-medicine Database. The search was undertaken in March 2005. Language was restricted to Chinese and English. Literature references were checked at the same time. Only RCTs were extracted and evaluated by two reviewers independently of each other. The statistical analysis was performed by RevMan4.2 software which was provided by the Cochrane Collaboration. A P value of triglyceride (LCT), and the combined results showed that the ST had significant effect on resting energy expenditure (weighted mean difference [WMD] =1.54, 95%CI [ 1.26, 1.82], ptriglycerides (WMD = -0.10, 95%CI [-0.30, 0.10], P=0.32). Only two RCTs compared ST with the physical mixture of medium- and long-chain triglyceride (MCT/LCT), data from trials were not combined due to clinical differences between trials, and conclusions can not be drew from the present data. ST appeared to be safe and well tolerated. Further trials are required, especially compared with the MCT/LCT, with sufficient size and rigorous design.

Registry-based randomized controlled trials merged the strength of randomized controlled trails and observational studies and give rise to more pragmatic trials.

Science.gov (United States)

Mathes, Tim; Buehn, Stefanie; Prengel, Peggy; Pieper, Dawid

2018-01-01

The objective of this study was to analyze the features of registry-based randomized trials (rRCTs). We systematically searched PubMed for rRCTs. Study selection was performed independently by two reviewers. We extracted all data in standardized tables and prepared descriptive summary statistics. The search resulted in 1,202 hits. We included 71 rRCTs. Most rRCTs were from Denmark and Sweden. Chronic conditions were considered in 82.2%. A preventive intervention was examined in 45.1%. The median of included patients was 2,000 (range: 69-246,079). Definition of the study population was mostly broad. Study procedures were regularly little standardized. The number of included and analyzed patients was the same in 82.1%. In half of the rRCTs, more than one registry was utilized. Various linkage techniques were used. In median, two outcomes were collected from the registry/ies. The median follow-up of the rRCTs was 5.3 years (range: 6 weeks to 27 years). Information on quality of registry data was reported in 11.3%. rRCTs can provide valid (randomization, low lost-to-follow-up rates, generalizable) patient important long-term comparative-effectiveness data for relative little effort. Researchers planning an RCT should always check whether existing registries can be used for data collection. Reporting on data quality must be improved for use in evidence synthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Reporting of Randomized Trials in Common Cancers in the Lay Media.

Science.gov (United States)

Ribnikar, Domen; Goldvaser, Hadar; Ocana, Alberto; Templeton, Arnoud J; Seruga, Bostjan; Amir, Eitan

2018-01-01

Limited data exist about the role of the lay media in the dissemination of results of randomized controlled trials (RCTs) in common cancers. Completed phase III RCTs evaluating new drugs in common cancers between January 2005 and October 2016 were identified from ClinicalTrials.gov. Lay media reporting was identified by searching LexisNexis Academic. Scientific reporting was defined as presentation at an academic conference or publication in full. Associations between reporting in the lay media before scientific reporting and study design and sponsorship were evaluated using logistic regression. Of 180 RCTs identified, 52% were reported in the lay media and in 27%, lay media reporting occurred before scientific reporting with an increasing trend over time (p = 0.009). Reporting in the lay media before scientific reporting was associated with positive results (OR: 2.10, p = 0.04), targeted therapy compared to chemotherapy (OR: 4.75, p = 0.006), immunotherapy compared to chemotherapy (OR: 7.60, p = 0.02), and prostate cancer compared to breast cancer (OR: 3.25, p = 0.02). Over a quarter of all RCTs in common cancers are reported in the lay media before they are reported scientifically with an increasing proportion over time. Positive trials, studies in prostate cancer, and trials of immunotherapy are associated with early reporting in the lay media. © 2017 S. Karger AG, Basel.

Randomized controlled psychotherapy trials in eating disorders: Improving their conduct, interpretation and usefulness.

Science.gov (United States)

Wade, Tracey D; Johnson, Catherine; Byrne, Susan M

2018-04-25

While randomized controlled trials (RCTs) inform the efficacy and effectiveness of treatments, we need to understand that even RCTs can be associated with sub-optimal execution. This is of special pertinence to eating disorders given the majority of treatment studies involving cognitive behaviour therapy are of poor quality with respect to managing risk of bias adequately. The current paper outlines the components of a good RCT for psychotherapy, and examines ways to improve the conduct, interpretation, and usefulness of RCTs. This includes managing reporting bias, recognizing the limits of randomization, applicability, and ethical considerations. We highlight a number of strategies for future research, including issues related to utilizing a variety of designs to examine treatment outcomes, integrity, openness and reproducibility. © 2018 Wiley Periodicals, Inc.

Event Rates in Randomized Clinical Trials Evaluating Cardiovascular Interventions and Devices

NARCIS (Netherlands)

Mahmoud, Karim D.; Lennon, Ryan J.; Holmes, David R.

2015-01-01

Randomized clinical trials (RCTs) are considered the gold standard for evidence-based medicine. However, an accurate estimation of the event rate is crucial for their ability to test clinical hypotheses. Overestimation of event rates reduces the required sample size but can compromise the

Vitamin D and Testosterone in Healthy Men: A Randomized Controlled Trial

NARCIS (Netherlands)

Lerchbaum, Elisabeth; Pilz, Stefan; Trummer, Christian; Schwetz, Verena; Pachernegg, Oliver; Heijboer, Annemieke C.; Obermayer-Pietsch, Barbara

2017-01-01

Available evidence shows an association of vitamin D with androgen levels in men. However, results from preliminary randomized controlled trials (RCTs) are conflicting. To evaluate whether vitamin D supplementation increases total testosterone (TT) levels in healthy men. The Graz Vitamin D&TT-RCT is

Inclusion and definition of acute renal dysfunction in critically ill patients in randomized controlled trials: a systematic review.

Science.gov (United States)

da Hora Passos, Rogerio; Ramos, Joao Gabriel Rosa; Gobatto, André; Caldas, Juliana; Macedo, Etienne; Batista, Paulo Benigno

2018-04-24

In evidence-based medicine, multicenter, prospective, randomized controlled trials (RCTs) are the gold standard for evaluating treatment benefits and ensuring the effectiveness of interventions. Patient-centered outcomes, such as mortality, are most often the preferred evaluated outcomes. While there is currently agreement on how to classify renal dysfunction in critically ill patients , the application frequency of this new classification system in RCTs has not previously been evaluated. In this study, we aim to assess the definition of renal dysfunction in multicenter RCTs involving critically ill patients that included mortality as a primary endpoint. A comprehensive search was conducted for publications reporting multicenter randomized controlled trials (RCTs) involving adult patients in intensive care units (ICUs) that included mortality as a primary outcome. MEDLINE and PUBMED were queried for relevant articles in core clinical journals published between May 2004 and December 2017. Of 418 articles reviewed, 46 multicenter RCTs with a primary endpoint related to mortality were included. Thirty-six (78.3%) of the trial reports provided information on renal function in the participants. Only seven articles (15.2%) included mean or median serum creatinine levels, mean creatinine clearance or estimated glomerular filtration rates. Sequential organ failure assessment (SOFA) score was the most commonly used definition of renal dysfunction (20 studies; 43.5%). Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease Improving Global Outcomes (KDIGO) criteria were used in five (10.9%) trials. In thirteen trials (28.3%), no renal dysfunction criteria were reported. Only one trial excluded patients with renal dysfunction, and it used urinary output or need for renal replacement therapy (RRT) as criteria for this diagnosis. The presence of renal dysfunction was included as a baseline patient characteristic in

Twenty-year perspective of randomized controlled trials for surgery of chronic nonspecific low back pain: citation bias and tangential knowledge.

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Andrade, Nicholas S; Flynn, John P; Bartanusz, Viktor

2013-11-01

After decades of clinical research, the role of surgery for chronic nonspecific low back pain (CNLBP) remains equivocal. Despite significant intellectual, human, and economic investments into randomized controlled trials (RCTs) in the past two decades, the role of surgery in the treatment for CNLBP has not been clarified. To delineate the historical research agenda of surgical RCTs for CNLBP performed between 1993 and 2012 investigating whether conclusions from earlier published trials influenced the choice of research questions of subsequent RCTs on elucidating the role of surgery in the management of CNLBP. Literature review. We searched the literature for all RCTs involving surgery for CNLBP. We reviewed relevant studies to identify the study question, comparator arms, and sample size. Randomized controlled trials were classified as "indication" trials if they evaluated the effectiveness of surgical therapy versus nonoperative care or as "technical" if they compared different surgical techniques, adjuncts, or procedures. We used citation analysis to determine the impact of trials on subsequent research in the field. Altogether 33 technical RCTs (3,790 patients) and 6 indication RCTs (981 patients) have been performed. Since 2007, despite the unclear benefits of surgery reported by the first four indication trials published in 2001 to 2006, technical trials have continued to predominate (16 vs. 2). Of the technical trials, types of instrumentation (13 trials, 1,332 patients), bone graft materials and substitutes (11 trials, 833 patients), and disc arthroplasty versus fusion (5 trials, 1,337 patients) were the most common comparisons made. Surgeon authors have predominantly cited one of the indication trials that reported more favorable results for surgery, despite a lack of superior methodology or sample size. Trials evaluating bone morphogenic protein, instrumentation, and disc arthroplasty were all cited more frequently than the largest trial of surgical versus

167: CRITICALLY APPRAISE OF THE REPORTING QUALITY OF RANDOMIZED CONTROLLED TRIALS ARTICLES IN THE FIELD OF DIABETES IN MEDICAL GUIDELINES IN IRAN

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Aletaha, Azadeh; Baradaran, Hamid Reza; Soltani, Akbar; Ramezani, Amir

2017-01-01

Background and aims To determine the quality of randomized controlled clinical trial reports in diabetes research in Iran and their presence in domestic and foreign credible guidelines which can imply whether randomized controlled trial articles in the field of diabetes are of good quality or not with respect to their high level of received citations, quality and credibility. Method We included RCTs conducted on Diabetes mellitus in Iran. Animal studies, educational, interventions, and non-randomized trials were excluded. This was a bibliographic study examining published journal articles involving RCTs in diabetes research from Iranian authors. A systematic search of ten databases(ISI Web of science, Scopus, PubMed, Science Direct, The Cochrane Library, Taylor & Francis Online, Biomed Central, EBSCO, ProQuest and OVID)were undertaken from July 2004–2014. We excluded duplicated publications reporting the same groups of participants and intervention two independent reviewers identify all eligible articles specifically designed data extraction form. Two reviewers assessed the quality of reporting by CONSORT 2010 (Consolidated Standards of Reporting Trials) checklist statement and also evaluate each article with Scientometry tools in 260 valid English diabetes guidelines. Result Overall, we included 185 RCTs on diabetes mellitus, One 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. From 185 articles, twelve articles (10%) are presented in 260 Guidelines. Conclusion The reporting quality of abstracts of RCTs

Neighborhood Effects in a Behavioral Randomized Controlled Trial

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Pruitt, Sandi L.; Leonard, Tammy; Murdoch, James; Hughes, Amy; McQueen, Amy; Gupta, Samir

2014-01-01

Randomized controlled trials (RCTs) of interventions intended to modify health behaviors may be influenced by neighborhood effects which can impede unbiased estimation of intervention effects. Examining a RCT designed to increase colorectal cancer (CRC) screening (N=5,628), we found statistically significant neighborhood effects: average CRC test use among neighboring study participants was significantly and positively associated with individual patient’s CRC test use. This potentially import...

Neighborhood effects in a behavioral randomized controlled trial.

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Pruitt, Sandi L; Leonard, Tammy; Murdoch, James; Hughes, Amy; McQueen, Amy; Gupta, Samir

2014-11-01

Randomized controlled trials (RCTs) of interventions intended to modify health behaviors may be influenced by neighborhood effects which can impede unbiased estimation of intervention effects. Examining a RCT designed to increase colorectal cancer (CRC) screening (N=5628), we found statistically significant neighborhood effects: average CRC test use among neighboring study participants was significantly and positively associated with individual patient's CRC test use. This potentially important spatially-varying covariate has not previously been considered in a RCT. Our results suggest that future RCTs of health behavior interventions should assess potential social interactions between participants, which may cause intervention arm contamination and may bias effect size estimation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Outcomes in registered, ongoing randomized controlled trials of patient education.

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Cécile Pino

Full Text Available BACKGROUND: With the increasing prevalence of chronic noncommunicable diseases, patient education is becoming important to strengthen disease prevention and control. We aimed to systematically determine the extent to which registered, ongoing randomized controlled trials (RCTs evaluated an educational intervention focus on patient-important outcomes (i.e., outcomes measuring patient health status and quality of life. METHODS: On May 6, 2009, we searched for all ongoing RCTs registered in the World Health Organization International Clinical Trials Registry platform. We used a standardized data extraction form to collect data and determined whether the outcomes assessed were 1 patient-important outcomes such as clinical events, functional status, pain, or quality of life or 2 surrogate outcomes, such as biological outcome, treatment adherence, or patient knowledge. PRINCIPAL FINDINGS: We selected 268 of the 642 potentially eligible studies and assessed a random sample of 150. Patient-important outcomes represented 54% (178 of 333 of all primary outcomes and 46% (286 of 623 of all secondary outcomes. Overall, 69% of trials (104 of 150 used at least one patient-important outcome as a primary outcome and 66% (99 of 150 as a secondary outcome. Finally, for 31% of trials (46 of 150, primary outcomes were only surrogate outcomes. The results varied by medical area. In neuropsychiatric disorders, patient important outcomes represented 84% (51 of 61 of primary outcomes, as compared with 54% (32 of 59 in malignant neoplasm and 18% (4 of 22 in diabetes mellitus trials. In addition, only 35% assessed the long-term impact of interventions (i.e., >6 months. CONCLUSIONS: There is a need to improve the relevance of outcomes and to assess the long term impact of educational interventions in RCTs.

Behavioral insights and business taxation: Evidence from two randomized controlled trials

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Biddle, Nicholas; Fels, Katja; Sinning, Mathias

2017-01-01

This paper presents the findings of two Randomized Controlled Trials (RCTs) that were conducted in collaboration with the Australian Taxation Office (ATO). The first trial tests the effect of changes to letters (timing, social norms, color, and provision of information about charitable donations) on response rates of businesses, the timing of payments and the amount of tax debt payments. The second trial consists of two parts. The first part aims to raise awareness of the relevance of tax deb...

Characteristics of randomized trials published in Latin America and the Caribbean according to funding source.

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Ludovic Reveiz

Full Text Available INTRODUCTION: Few studies have assessed the nature and quality of randomized controlled trials (RCTs in Latin America and the Caribbean (LAC. METHODS AND FINDINGS: The aims of this systematic review are to evaluate the characteristics (including the risk of bias assessment of RCT conducted in LAC according to funding source. A review of RCTs published in 2010 in which the author's affiliation was from LAC was performed in PubMed and LILACS. Two reviewers independently extracted data and assessed the risk of bias. The primary outcomes were risk of bias assessment and funding source. A total of 1,695 references were found in PubMed and LILACS databases, of which 526 were RCTs (N = 73.513 participants. English was the dominant publication language (93% and most of the RCTs were published in non-LAC journals (84.2%. Only five of the 19 identified countries accounted for nearly 95% of all RCTs conducted in the region (Brazil 70.9%, Mexico 10.1%, Argentina 5.9%, Colombia 3.8%, and Chile 3.4%. Few RCTs covered priority areas related with Millennium Development Goals like maternal health (6.7% or high priority infectious diseases (3.8%. Regarding children, 3.6% and 0.4% RCT evaluated nutrition and diarrhea interventions respectively but none pneumonia. As a comparison, aesthetic and sport related interventions account for 4.6% of all trials. A random sample of RCTs (n = 358 was assessed for funding source: exclusively public (33.8%; private (e.g. pharmaceutical company (15.3%; other (e.g. mixed, NGO (15.1%; no funding (35.8%. Overall assessments for risk of bias showed no statistically significant differences between RCTs and type of funding source. Statistically significant differences favoring private and others type of funding was found when assessing trial registration and conflict of interest reporting. CONCLUSION: Findings of this study could be used to provide more direction for future research to facilitate innovation, improve health

Characteristics of randomized trials published in Latin America and the Caribbean according to funding source.

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Reveiz, Ludovic; Sangalang, Stephanie; Glujovsky, Demian; Pinzon, Carlos E; Asenjo Lobos, Claudia; Cortes, Marcela; Cañón, Martin; Bardach, Ariel; Bonfill, Xavier

2013-01-01

Few studies have assessed the nature and quality of randomized controlled trials (RCTs) in Latin America and the Caribbean (LAC). The aims of this systematic review are to evaluate the characteristics (including the risk of bias assessment) of RCT conducted in LAC according to funding source. A review of RCTs published in 2010 in which the author's affiliation was from LAC was performed in PubMed and LILACS. Two reviewers independently extracted data and assessed the risk of bias. The primary outcomes were risk of bias assessment and funding source. A total of 1,695 references were found in PubMed and LILACS databases, of which 526 were RCTs (N = 73.513 participants). English was the dominant publication language (93%) and most of the RCTs were published in non-LAC journals (84.2%). Only five of the 19 identified countries accounted for nearly 95% of all RCTs conducted in the region (Brazil 70.9%, Mexico 10.1%, Argentina 5.9%, Colombia 3.8%, and Chile 3.4%). Few RCTs covered priority areas related with Millennium Development Goals like maternal health (6.7%) or high priority infectious diseases (3.8%). Regarding children, 3.6% and 0.4% RCT evaluated nutrition and diarrhea interventions respectively but none pneumonia. As a comparison, aesthetic and sport related interventions account for 4.6% of all trials. A random sample of RCTs (n = 358) was assessed for funding source: exclusively public (33.8%); private (e.g. pharmaceutical company) (15.3%); other (e.g. mixed, NGO) (15.1%); no funding (35.8%). Overall assessments for risk of bias showed no statistically significant differences between RCTs and type of funding source. Statistically significant differences favoring private and others type of funding was found when assessing trial registration and conflict of interest reporting. Findings of this study could be used to provide more direction for future research to facilitate innovation, improve health outcomes or address priority health problems.

Randomized controlled trials and neuro-oncology: should alternative designs be considered?

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Mansouri, Alireza; Shin, Samuel; Cooper, Benjamin; Srivastava, Archita; Bhandari, Mohit; Kondziolka, Douglas

2015-09-01

Deficiencies in design and reporting of randomized controlled trials (RCTs) hinders interpretability and critical appraisal. The reporting quality of recent RCTs in neuro-oncology was analyzed to assess adequacy of design and reporting. The MEDLINE and EMBASE databases were searched to identify non-surgical RCTs (years 2005-2014, inclusive). The CONSORT and Jadad scales were used to assess the quality of design/reporting. Studies published in 2005-2010 were compared as a cohort against studies published in 2011-2014, in terms of general characteristics and reporting quality. A PRECIS-based scale was used to designate studies on the pragmatic-explanatory continuum. Spearman's test was used to assess correlations. Regression analysis was used to assess associations. Overall 68 RCTs were identified. Studies were often chemotherapy-based (n = 41 studies) focusing upon high grade gliomas (46 %) and metastases (41 %) as the top pathologies. Multi-center trials (71 %) were frequent. The overall median CONSORT and Jadad scores were 34.5 (maximum 44) and 2 (maximum 5), respectively; these scores were similar in radiation and chemotherapy-based trials. Major areas of deficiency pertained to allocation concealment, implementation of methods, and blinding whereby less than 20 % of articles fulfilled all criteria. Description of intervention, random sequence generation, and the details regarding recruitment were also deficient; less than 50 % of studies fulfilled all criteria. Description of sample size calculations and blinding improved in later published cohorts. Journal impact factor was significantly associated with higher quality (p = 0.04). Large academic consortia, multi-center designs, ITT analysis, collaboration with biostatisticians, larger sample sizes, and studies with pragmatic objectives were more likely to achieve positive primary outcomes on univariate analysis; none of these variables were significant on multivariate analysis. Deficiencies in the

[Analysing the defect of control design of acupuncture: taking RCTs of treating simple obesity with acupuncture for example].

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Zeng, Yi; Qi, Shulan; Meng, Xing; Chen, Yinyin

2018-03-12

By analysing the defect of control design in randomized controlled trials (RCTs) of simple obesity treated with acupuncture and using acupuncture as the contrast, presenting the essential factors which should be taken into account as designing the control of clinical trial to further improve the clinical research. Setting RCTs of acupuncture treating simple obesity as a example, we searched RCTs of acupuncture treating simple obesity with acupuncture control. According to the characteristics of acupuncture therapy, this research sorted and analysed the control approach of intervention from aspects of acupoint selection, the penetration of needle, the depth of insertion, etc, then calculated the amount of difference factor between the two groups and analyzed the rationality. In 15 RCTs meeting the inclusion criterias, 7 published in English, 8 in Chinese, the amount of difference factors between two groups greater than 1 was 6 (40%), 4 published in English abroad, 2 in Chinese, while only 1 was 9 (60%), 3 published in English, 6 in Chinese. Control design of acupuncture in some clinical RCTs is unreasonable for not considering the amount of difference factors between the two groups.

Acupuncture for treating polycystic ovary syndrome: guidance for future randomized controlled trials

OpenAIRE

Wu, Y; Robinson, N; Hardiman, PJ; Taw, MB; Zhou, J; Wang, FF; Qu, F

2016-01-01

Objective: To provide guidance for future randomized controlled trials (RCTs) based on a review concerning acupuncture for treating polycystic ovary syndrome (PCOS). Methods: A comprehensive literature search was conducted in October 2015 using MEDLINE, EMBASE, SCISEARCH, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Menstrual Disorders and Subfertility Group trials register, Allied and Complementary Medicine (AMED), China National Knowledge Infrastructure (CNKI), and...

Reporting Quality of Randomized, Controlled Trials Evaluating Combined Chemoradiotherapy in Nasopharyngeal Carcinoma

International Nuclear Information System (INIS)

Chen, Yu-Pei; Chen, Lei; Li, Wen-Fei; Lee, Anne W.M.; Vermorken, Jan B.; Wee, Joseph; O'Sullivan, Brian; Eisbruch, Avraham; Lin, Jin-Ching; Mai, Hai-Qiang; Zhang, Li; Guo, Ying; Lin, Ai-Hua; Sun, Ying

2017-01-01

Purpose: To comprehensively assess the reporting quality of randomized, controlled trials (RCTs) in nasopharyngeal carcinoma (NPC), and to identify significant predictors of quality. Methods and Materials: Two investigators searched MEDLINE and EMBASE for RCTs published between January 1988 and December 2015 that assessed the effect of combined chemoradiotherapy for NPC. The overall quality of each report was assessed using a 28-point overall quality score (OQS) based on the 2010 Consolidated Standards of Reporting Trials (CONSORT) statement. To provide baseline data for further evaluation, we also investigated the reporting quality of certain important issues in detail, including key methodologic items (allocation concealment, blinding, intention-to-treat principle), endpoints, follow-up, subgroup analyses, and adverse events. Results: We retrieved 24 relevant RCTs including 6591 patients. Median 2010 OQS was 15.5 (range, 10-24). Half of the items in the 2010 OQS were poorly reported in at least 40% of trials. Multivariable regression models revealed that publication after 2010 and high impact factor were significant predictors of improved 2010 OQS. Additionally, many issues that we consider significant were not reported adequately. Conclusions: Despite publication of the CONSORT statement more than a decade ago, overall reporting quality for RCTs in NPC was unsatisfactory. Additionally, substantial selectivity and heterogeneity exists in reporting of certain crucial issues. This survey provides the first prompt for NPC trial investigators to improve reporting quality according to the CONSORT statement; increased scrutiny and diligence by editors and peer reviewers is also required.

Reporting Quality of Randomized, Controlled Trials Evaluating Combined Chemoradiotherapy in Nasopharyngeal Carcinoma

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Chen, Yu-Pei; Chen, Lei; Li, Wen-Fei [Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre of Cancer Medicine, Guangzhou (China); Lee, Anne W.M. [Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen (China); Vermorken, Jan B. [Department of Medical Oncology, Antwerp University Hospital, Edegem (Belgium); Wee, Joseph [Department of Radiation Oncology, National Cancer Centre Singapore (Singapore); O' Sullivan, Brian [Department of Radiation Oncology, University of Toronto, Ontario Cancer Institute, University Health Network, Toronto, Ontario (Canada); Eisbruch, Avraham [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Lin, Jin-Ching [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Mai, Hai-Qiang [Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre of Cancer Medicine, Guangzhou (China); Zhang, Li [Department of Medical Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre of Cancer Medicine, Guangzhou (China); Guo, Ying [Clinical Trials Centre, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre of Cancer Medicine, Guangzhou (China); Lin, Ai-Hua [Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou (China); Sun, Ying [Department of Radiation Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre of Cancer Medicine, Guangzhou (China); and others

2017-05-01

Purpose: To comprehensively assess the reporting quality of randomized, controlled trials (RCTs) in nasopharyngeal carcinoma (NPC), and to identify significant predictors of quality. Methods and Materials: Two investigators searched MEDLINE and EMBASE for RCTs published between January 1988 and December 2015 that assessed the effect of combined chemoradiotherapy for NPC. The overall quality of each report was assessed using a 28-point overall quality score (OQS) based on the 2010 Consolidated Standards of Reporting Trials (CONSORT) statement. To provide baseline data for further evaluation, we also investigated the reporting quality of certain important issues in detail, including key methodologic items (allocation concealment, blinding, intention-to-treat principle), endpoints, follow-up, subgroup analyses, and adverse events. Results: We retrieved 24 relevant RCTs including 6591 patients. Median 2010 OQS was 15.5 (range, 10-24). Half of the items in the 2010 OQS were poorly reported in at least 40% of trials. Multivariable regression models revealed that publication after 2010 and high impact factor were significant predictors of improved 2010 OQS. Additionally, many issues that we consider significant were not reported adequately. Conclusions: Despite publication of the CONSORT statement more than a decade ago, overall reporting quality for RCTs in NPC was unsatisfactory. Additionally, substantial selectivity and heterogeneity exists in reporting of certain crucial issues. This survey provides the first prompt for NPC trial investigators to improve reporting quality according to the CONSORT statement; increased scrutiny and diligence by editors and peer reviewers is also required.

Expanding the Evidence Base: Comparing Randomized Controlled Trials and Observational Studies of Statins

NARCIS (Netherlands)

Atar, Dan; Ong, Seleen; Lansberg, Peter J.

2015-01-01

It is widely accepted that randomized controlled trials (RCTs) are the gold standard for demonstrating the efficacy of a given therapy (results under ideal conditions). Observational studies, on the other hand, can complement this by demonstrating effectiveness (results under real-world conditions).

QUINT : A tool to detect qualitative treatment-subgroup interactions in randomized controlled trials

NARCIS (Netherlands)

Doove, L.L.; Van Deun, K.; Dusseldorp, E.; van Mechelen, I.

2016-01-01

Objective: The detection of subgroups involved in qualitative treatment–subgroup interactions (i.e., for one subgroup of clients treatment A outperforms treatment B, whereas for another the reverse holds true) is crucial for personalized health. In typical Randomized Controlled Trials (RCTs), the

Inadequate description of educational interventions in ongoing randomized controlled trials

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Pino Cécile

2012-05-01

Full Text Available Abstract Background The registration of clinical trials has been promoted to prevent publication bias and increase research transparency. Despite general agreement about the minimum amount of information needed for trial registration, we lack clear guidance on descriptions of non-pharmacologic interventions in trial registries. We aimed to evaluate the quality of registry descriptions of non-pharmacologic interventions assessed in ongoing randomized controlled trials (RCTs of patient education. Methods On 6 May 2009, we searched for all ongoing RCTs registered in the 10 trial registries accessible through the World Health Organization International Clinical Trials Registry Platform. We included trials evaluating an educational intervention (that is, designed to teach or train patients about their own health and dedicated to participants, their family members or home caregivers. We used a standardized data extraction form to collect data related to the description of the experimental intervention, the centers, and the caregivers. Results We selected 268 of 642 potentially eligible studies and appraised a random sample of 150 records. All selected trials were registered in 4 registers, mainly ClinicalTrials.gov (61%. The median [interquartile range] target sample size was 205 [100 to 400] patients. The comparator was mainly usual care (47% or active treatment (47%. A minority of records (17%, 95% CI 11 to 23% reported an overall adequate description of the intervention (that is, description that reported the content, mode of delivery, number, frequency, duration of sessions and overall duration of the intervention. Further, for most reports (59%, important information about the content of the intervention was missing. The description of the mode of delivery of the intervention was reported for 52% of studies, the number of sessions for 74%, the frequency of sessions for 58%, the duration of each session for 45% and the overall duration for 63

Philosophers assess randomized clinical trials: the need for dialogue.

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Miké, V

1989-09-01

In recent years a growing number of professional philosophers have joined in the controversy over ethical aspects of randomized clinical trials (RCTs). Morally questionable in their utilitarian approach, RCTs are claimed by some to be in direct violation of the second form of Kant's Categorical Imperative. But the arguments used in these critiques at times derive from a lack of insight into basic statistical procedures and the realities of the biomedical research process. Presented to physicians and other nonspecialists, including the lay public, such distortions can be harmful. Given the great complexity of statistical methodology and the anomalous nature of concepts of evidence, more sustained input into the interdisciplinary dialogue is needed from the statistical profession.

Review of randomized controlled trials of nutritional supplementation in people living with HIV

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Sneij A

2016-04-01

Full Text Available Alicia Sneij, Adriana Campa, Marianna K Baum Stempel College of Public Health and Social Work, Florida International University, Modesto Maidique Campus, Miami, FL, USA Background: Nutritional deficiencies are widespread in people living with HIV (PLWH, prior to the antiretroviral treatment (ART. Nutrient deficiencies and other nutrition-related conditions, however, have been identified in patients receiving ART. Trials of nutritional supplementation have been conducted to alleviate these nutritional conditions and improve or reverse nutrition-related outcomes. This review aims to evaluate the benefits of supplementation, its unintended adverse effects, and the difference in approach and focus, research design, formulations, and outcomes between those randomized clinical trials (RCTs conducted before and after the initiation of ART. Methods: An evidence-based systematic review of the literature was conducted using electronic databases and the resources of the Florida International University Research Library. Forty-two RCTs were selected for review, and their design and outcomes were compared and contrasted conceptually and in the form of tables. Results: Most of the RCTs (n=31 were conducted before the advent of ART, and their aims were delaying disease progression, reversing malnutrition, and improving pregnancy outcomes in women and infants infected with HIV. The RCTs conducted with coadministration of ART were fewer (n=11, with relative smaller sample size, of shorter duration, and mainly focused on preventing or ameliorating the nutrition-related conditions generated by the chronic infection, its treatment, and the aging of PLWH. Conclusion: As ART is becoming more accessible worldwide, and people are living longer with the disease, more longitudinal trials of nutritional interventions with larger sample sizes are needed to study the nutritional consequences and potential treatments for PLWH. Keywords: HIV, antiretroviral therapy

No differential attrition was found in randomized controlled trials published in general medical journals: a meta-analysis.

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Crutzen, Rik; Viechtbauer, Wolfgang; Kotz, Daniel; Spigt, Mark

2013-09-01

Differential attrition is regarded as a major threat to the internal validity of a randomized controlled trial (RCT). This study identifies the degree of differential attrition in RCTs covering a broad spectrum of clinical areas and factors that are related to this. A PubMed search was conducted to obtain a random sample of 100 RCTs published between 2008 and 2010 in journals from the ISI Web of Knowledge(SM) category of medicine, general and internal. Eligibility criteria for selecting studies were primary publications of two-arm parallel randomized clinical trials, containing human participants and one or multiple follow-up measurements whose availability depended on the patients' willingness to participate. A significant amount of differential attrition was observed in 8% of the trials. The average differential attrition rate was 0.99 (95% confidence interval: 0.97-1.01), indicating no general difference in attrition rates between intervention and control groups. Moreover, no indication of heterogeneity was found, suggesting that the occurrence of differential attrition in the published literature is mostly a chance finding, unrelated to any particular design factors. Differential attrition did not generally occur in RCTs covering a broad spectrum of clinical areas within general and internal medicine. Copyright © 2013 Elsevier Inc. All rights reserved.

Randomized controlled trials of HIV/AIDS prevention and treatment in Africa: results from the Cochrane HIV/AIDS Specialized Register.

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Babalwa Zani

Full Text Available INTRODUCTION: To effectively address HIV/AIDS in Africa, evidence on preventing new infections and providing effective treatment is needed. Ideally, decisions on which interventions are effective should be based on evidence from randomized controlled trials (RCTs. Our previous research described African RCTs of HIV/AIDS reported between 1987 and 2003. This study updates that analysis with RCTs published between 2004 and 2008. OBJECTIVES: To describe RCTs of HIV/AIDS conducted in Africa and reported between 2004 and 2008. METHODS: We searched the Cochrane HIV/AIDS Specialized Register in September 2009. Two researchers independently evaluated studies for inclusion and extracted data using standardized forms. Details included location of trials, interventions, methodological quality, location of principal investigators and funders. RESULTS: Our search identified 834 RCTs, with 68 conducted in Africa. Forty-three assessed prevention-interventions and 25 treatment-interventions. Fifteen of the 43 prevention RCTs focused on preventing mother-to-child HIV transmission. Thirteen of the 25 treatment trials focused on opportunistic infections. Trials were conducted in 16 countries with most in South Africa (20, Zambia (12 and Zimbabwe (9. The median sample size was 628 (range 33-9645. Methods used for the generation of the allocation sequence and allocation concealment were adequate in 38 and 32 trials, respectively, and 58 reports included a CONSORT recommended flow diagram. Twenty-nine principal investigators resided in the United States of America (USA and 18 were from African countries. Trials were co-funded by different agencies with most of the funding obtained from USA governmental and non-governmental agencies. Nineteen pharmaceutical companies provided partial funding to 15 RCTs and African agencies co-funded 17 RCTs. Ethical approval was reported in 65 trials and informed consent in 61 trials. CONCLUSION: Prevention trials dominate the trial

Systematic Review of Randomized Clinical Trials on Safety and Efficacy of Pharmacological and Nonpharmacological Treatments for Retinitis Pigmentosa

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Marta Sacchetti

2015-01-01

Full Text Available Aims. Several treatments have been proposed to slow down progression of Retinitis pigmentosa (RP, a hereditary retinal degenerative condition leading to severe visual impairment. The aim of this study is to systematically review data from randomized clinical trials (RCTs evaluating safety and efficacy of medical interventions for the treatment of RP. Methods. Randomized clinical trials on medical treatments for syndromic and nonsyndromic RP published up to December 2014 were included in the review. Visual acuity, visual field, electroretinogram, and adverse events were used as outcome measures. Results. The 19 RCTs included in this systematic review included trials on hyperbaric oxygen delivery, topical brimonidine tartrate, vitamins, docosahexaenoic acid, gangliosides, lutein, oral nilvadipine, ciliary neurotrophic factor, and valproic acid. All treatments proved safe but did not show significant benefit on visual function. Long term supplementation with vitamin A showed a significantly slower decline rate in electroretinogram amplitude. Conclusions. Although all medical treatments for RP appear safe, evidence emerging from RCTs is limited since they do not present comparable results suitable for quantitative statistical analysis. The limited number of RCTs, the poor clinical results, and the heterogeneity among studies negatively influence the strength of recommendations for the long term management of RP patients.

Efficacy of auriculotherapy for constipation in adults: a systematic review and meta-analysis of randomized controlled trials.

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Yang, Li-Hua; Duan, Pei-Bei; Du, Shi-Zheng; Sun, Jin-Fang; Mei, Si-Juan; Wang, Xiao-Qing; Zhang, Yuan-Yuan

2014-08-01

To assess the clinical evidence of auriculotherapy for constipation treatment and to identify the efficacy of groups using Semen vaccariae or magnetic pellets as taped objects in managing constipation. Databases were searched, including five English-language databases (the Cochrane Library, PubMed, Embase, CINAHL, and AMED) and four Chinese medical databases. Only randomized controlled trials were included in the review process. Critical appraisal was conducted using the Cochrane risk of bias tool. Seventeen randomized, controlled trials (RCTs) met the inclusion criteria, of which 2 had low risk of bias. The primary outcome measures were the improvement rate and total effective rate. A meta-analysis of 15 RCTs showed a moderate, significant effect of auriculotherapy in managing constipation compared with controls (relative risk [RR], 2.06; 95% confidence interval [CI], 1.52- 2.79; pcultural and geographic differences. Further rigorous RCTs from around the world are warranted to confirm the effect and safety of auriculotherapy for constipation.

Reporting of symptoms in randomized controlled trials of atopic eczema treatments: a systematic review.

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Gerbens, L A A; Chalmers, J R; Rogers, N K; Nankervis, H; Spuls, P I

2016-10-01

'Symptoms' is a core outcome domain for atopic eczema (AE) trials, agreed by consensus as part of the Harmonising Outcome Measures for Eczema (HOME) initiative. To standardize and validate the core domain symptoms and symptom instruments for AE trials the HOME roadmap is followed. Its first step is to establish if and how symptoms have been measured in published AE treatment trials. Therefore the Global Resource for Eczema Trials database was used to collect all randomized controlled trials (RCTs) of treatments for AE between January 2000 and April 2014. Study selection and data extraction were performed by three reviewers independently. We identified the use of symptoms in 295 of 378 trials (78%). Symptoms as a primary end point were applied by 147 RCTs (50%). Seventeen different symptoms were measured, but mostly itch and sleep loss. Symptoms were assessed by only 37% of trials by a stand-alone symptom measurement. Overall 63% of RCTs used a composite instrument, and 30 different instruments were identified. The Scoring Atopic Dermatitis (SCORAD) index was the most commonly applied, but only 23% of RCTs reported the SCORAD symptom score separately. This systematic review demonstrates that symptoms, most frequently itch and sleep loss, are commonly reported in AE treatment trials, but are measured using many different instruments. Often symptoms are evaluated as part of a composite instrument, and currently it is not possible to extract symptoms-only data from most published studies. Future trials should report symptom scores to permit meta-analysis of the core outcomes. © 2016 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

Association between B vitamins supplementation and risk of cardiovascular outcomes: a cumulative meta-analysis of randomized controlled trials.

Directory of Open Access Journals (Sweden)

Chi Zhang

Full Text Available BACKGROUND: Observational studies suggest that B vitamin supplementation reduces cardiovascular risk in adults, but this association remains controversial. This study aimed to summarize the evidence from randomized controlled trials (RCTs investigating B vitamin supplementation for the primary or secondary prevention of major adverse cardiovascular outcomes and to perform a cumulative meta-analysis to determine the evidence base. METHODOLOGY AND PRINCIPAL FINDINGS: In April 2013, we searched PubMed, Embase, and the Cochrane Library to identify relevant RCTs. We included RCTs investigating the effect of B vitamin supplementation on cardiovascular outcome. Relative risk (RR was used to measure the effect using a random-effect model. Statistical heterogeneity scores were assessed using the Q statistic. We included data on 57,952 individuals from 24 RCTs: 12 primary prevention trials and 12 secondary prevention trials. In 23 of these trials, 10,917 major adverse cardiovascular events (MACE occurred; in 20 trials, 7,203 deaths occurred; in 15 trials, 3,422 cardiac deaths occurred; in 19 trials, 3,623 myocardial infarctions (MI occurred; and in 18 trials, 2,465 strokes occurred. B vitamin supplementation had little or no effect on the incidence of MACE (RR, 0.98; 95% confidence interval [CI]: 0.93-1.03; P = 0.37, total mortality (RR, 1.01; 95% CI: 0.97-1.05; P = 0.77, cardiac death (RR, 0.96; 95% CI: 0.90-1.02; P = 0.21, MI (RR, 0.99; 95% CI: 0.93-1.06; P = 0.82, or stroke (RR, 0.94; 95% CI: 0.85-1.03; P = 0.18. CONCLUSION/SIGNIFICANCE: B vitamin supplementation, when used for primary or secondary prevention, is not associated with a reduction in MACE, total mortality, cardiac death, MI, or stroke.

The effect of COPD severity and study duration on exacerbation outcome in randomized controlled trials

NARCIS (Netherlands)

Eriksson, Goran; Calverley, Peter M.; Jenkins, Christine R.; Anzueto, Antonio R.; Make, Barry J.; Lindberg, Magnus; Fageras, Malin; Postma, Dirkje S.

2017-01-01

Background: When discontinuation in COPD randomized controlled trials (RCTs) is unevenly distributed between treatments (differential dropout), the capacity to demonstrate treatment effects may be reduced. We investigated the impact of the time of differential dropout on exacerbation outcomes in

Evaluation of Wet Cupping Therapy: Systematic Review of Randomized Clinical Trials.

Science.gov (United States)

Al Bedah, Abdullah M N; Khalil, Mohamed K M; Posadzki, Paul; Sohaibani, Imen; Aboushanab, Tamer Shaaban; AlQaed, Meshari; Ali, Gazzaffi I M

2016-10-01

Wet cupping is a widely used traditional therapy in many countries, which justifies a continuous scientific evaluation of its efficacy and safety. To perform a systematic review to critically evaluate and update the available evidence of wet cupping in traditional and complementary medicine. Ten electronic databases were searched from their inceptions to February 2016. Included studies were randomized clinical trials (RCTs) that evaluated wet cupping against any type of control interventions in patients with any clinical condition, as well as healthy individuals. Cochrane risk of bias tool was used to appraise the included RCTs. Fourteen RCTs met the eligibility criteria. The included studies evaluated the following clinical conditions: nonspecific low back pain (NSLBP), hypertension, brachialgia, carpal tunnel syndrome (CTS), chronic neck pain, metabolic syndrome, migraine headaches, oxygen saturation in smokers with chronic obstructive pulmonary disease (COPD), and oral and genital ulcers due to Behçet disease. Two RCTs evaluated physiologic and biochemical parameters of healthy individuals. Overall, 9 RCTs favored wet cupping over various control interventions in NSLBP (n = 2), hypertension (n = 1), brachialgia (n = 1), CTS (n = 1), chronic neck pain (n = 2), oxygen saturation in smokers with COPD (n = 1), and oral and genital ulcers due to Behçet disease (n = 1). Five RCTs showed no statistically significant between-group differences: NSLBP (n = 1), metabolic syndrome (n = 1), migraine headaches (n = 1), and physiologic and biochemical parameters of healthy individuals (n = 2). Included RCTs had a variable risk of bias across all domains and suffered methodologic limitations. There is a promising evidence in favor of the use of wet cupping for musculoskeletal pain, specifically NSLBP, neck pain, CTS, and brachialgia. Better-quality trials are needed to generate solid evidence and firmly inform policy makers.

Commentary: Randomized controlled trials in autism spectrum disorder: state of the field and challenges for the future.

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Simonoff, Emily

2018-04-01

This issue of the Journal includes two articles summarizing the evidence from clinical trials aimed at improving symptoms of autism. French and Kennedy (Journal of Child Psychology and Psychiatry, 2018, xx, xxxx) systematically review randomized controlled trials (RCTs) aimed at an "early intervention" and focus on trials including children with or at risk of autism under age 6 years. Although no type of intervention were excluded from their review, none of the included 48 RCTs employed pharmacological modalities and the overwhelming majority tested psychological/behavioural interventions aimed at modifying aspects of observed behaviours that are abnormal in children with autism. Using the standard Cochrane tool for evaluating risk of bias, French and Kennedy conclude that many RCTs are of low quality, which throws into question the reliance that should be placed on the findings. © 2018 Association for Child and Adolescent Mental Health.

Progress and problems for randomized clinical trials: from streptomycin to the era of megatrials.

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Hilbrich, Lutz; Sleight, Peter

2006-09-01

Randomized clinical trials (RCTs) are the definitive contributors to evidence-based medicine. RCTs assessing serious outcomes in cardiovascular disease have grown, with 'megatrials' becoming more common with the realization that wrong conclusions resulted from random error in inadequately sized trials. Simple design and a heterogeneous patient population were early features, but multinational trials have increased in scientific, logistical, bureaucratic, regulatory, and legal complexity. These studies now exceed the financial means of academia or medical charities. Governments have left the bill with the pharmaceutical industry, encouraging a symbiosis with academics, who contribute medical and scientific expertise, and access to patients. Industry provides pharmacological, pharmaceutical, technical and regulatory know-how, good clinical practice expertise, and legal assistance during the trial. Study supervision is then in the hands of an independent steering committee and associated subcommittees, until appropriate dissemination of results. Prospectively defined interaction with the sponsor facilitates unbiased design and conduct, but arrangements need careful implementation to avoid conflicts of interest. The patient is protected by a strong data safety monitoring board that is wholly independent. Megatrials are under threat from over-regulation, increasing costs, and difficulties in execution. These issues merit urgent public and political education and debate.

Two Randomized Trials Provide No Consistent Evidence for Nonmusical Cognitive Benefits of Brief Preschool Music Enrichment

OpenAIRE

Mehr, Samuel A.; Schachner, Adena; Katz, Rachel C.; Spelke, Elizabeth S.

2013-01-01

Young children regularly engage in musical activities, but the effects of early music education on children’s cognitive development are unknown. While some studies have found associations between musical training in childhood and later nonmusical cognitive outcomes, few randomized controlled trials (RCTs) have been employed to assess causal effects of music lessons on child cognition and no clear pattern of results has emerged. We conducted two RCTs  with preschool children investigating the ...

Identifying randomized clinical trials in Spanish-language dermatology journals.

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Sanclemente, G; Pardo, H; Sánchez, S; Bonfill, X

2015-06-01

The necessary foundation for good clinical practice lies in knowledge derived from clinical research. Evidence from randomized clinical trials (RCTs) is the pillar on which decisions about therapy are based. To search exhaustively and rigorously to identify RCTs in dermatology journals published in Spanish. We located dermatology journals through the following search engines and indexes: PubMed, LILACS, SciELO, Periódica, Latindex, Índice Médico Español, C-17, IBECS, EMBASE, and IMBIOMED. We also sought information through dermatology associations and dermatologists in countries where Spanish was the usual language of publication, and we searched the Internet (Google). Afterwards we searched the journals electronically and manually to identify RCTs in all available volumes and issues, checking from the year publication started through 2012. Of 28 journals identified, we included 21 in the search. We found a total of 144 RCTs published since 1969; 78 (54%) were in Latin American journals and 66 (46%) were in Spanish journals. The most frequent disease contexts for RCTs in Spanish journals were psoriasis, mycoses, and acne vulgaris. In Latin American journals, the most frequent disease contexts were common warts, mycoses, acne vulgaris, and skin ulcers on the lower limbs. Manual searches identified more RCTs than electronic searches. Manual searches found a larger number of RCTs. Relatively fewer RCTs are published in Spanish and Latin American journals than in English-language journals. Internet facilitated access to full texts published by many journals; however, free open access to these texts is still unavailable and a large number of journal issues are still not posted online. Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.

A Mock Randomized Controlled Trial With Audience Response Technology for Teaching and Learning Epidemiology.

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Baker, Philip R A; Francis, Daniel P; Cathcart, Abby

2017-04-01

The study's objective was to apply and assess an active learning approach to epidemiology and critical appraisal. Active learning comprised a mock, randomized controlled trial (RCT) conducted with learners in 3 countries. The mock trial consisted of blindly eating red Smarties candy (intervention) compared to yellow Smarties (control) to determine whether red Smarties increase happiness. Audience response devices were employed with the 3-fold purposes to produce outcome data for analysis of the effects of red Smarties, identify baseline and subsequent changes in participant's knowledge and confidence in understanding of RCTs, and assess the teaching approach. Of those attending, 82% (117 of 143 learners) participated in the trial component. Participating in the mock trial was a positive experience, and the use of the technology aided learning. The trial produced data that learners analyzed in "real time" during the class. The mock RCT is a fun and engaging approach to teaching RCTs and helping students to develop skills in critical appraisal.

Transparency of outcome reporting and trial registration of randomized controlled trials in top psychosomatic and behavioral health journals: A systematic review.

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Milette, Katherine; Roseman, Michelle; Thombs, Brett D

2011-03-01

The most reliable evidence for evaluating healthcare interventions comes from well-designed and conducted randomized controlled trials (RCTs). The extent to which published RCTs reflect the efficacy of interventions, however, depends on the completeness and accuracy of published results. The Consolidated Standards of Reporting Trials statement, initially developed in 1996, provides guidelines intended to improve the transparency of published RCT reports. A policy of the International Committee of Medical Journal Editors, initiated in 2005, requires clinical trials published in member journals to be registered in publicly accessible registries prior to patient enrollment. The objective of this study was to assess the clarity of outcome reporting, proportion of registered trials, and adequacy of outcome registration in RCTs published in top behavioral health journals. Eligible studies were primary or secondary reports of RCTs published in Annals of Behavioral Medicine, Health Psychology, Journal of Psychosomatic Research, and Psychosomatic Medicine from January 2008 to September 2009. Data were extracted for each study on adequacy of outcome reporting and registration. Of 63 articles reviewed, only 25 (39.7%) had adequately declared primary or secondary outcomes, whereas 38 (60.3%) had multiple primary outcomes or did not define outcomes. Only 13 studies (20.6%) were registered. Only 1 study registered sufficiently precise outcome information to compare with published outcomes, and registered and published outcomes were discrepant in that study. Greater attention to outcome reporting and trial registration by researchers, peer reviewers, and journal editors will increase the likelihood that effective behavioral health interventions are readily identified and made available to patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Reassessing RCTs as the "Gold Standard": Synergy Not Separatism in Evaluation Designs

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Hanley, Pam; Chambers, Bette; Haslam, Jonathan

2016-01-01

Randomised controlled trials (RCTs) are increasingly used to evaluate educational interventions in the UK. However, RCTs remain controversial for some elements of the research community. This paper argues that the widespread use of the term "gold standard" to describe RCTs is problematic, as it implies that other research methods are…

Effects of trans fatty acids on glucose homeostasis: a meta-analysis of randomized, placebo-controlled clinical trials123

OpenAIRE

Aronis, Konstantinos N; Khan, Sami M; Mantzoros, Christos S

2012-01-01

Background: Although evidence from cohort studies has suggested that trans fatty acid (TFA) consumption may be associated with insulin resistance and diabetes, randomized placebo-controlled trials (RCTs) have yielded conflicting results.

Acupuncture for Children with Autism Spectrum Disorders: A Systematic Review of Randomized Clinical Trials

Science.gov (United States)

Lee, Myeong Soo; Choi, Tae-Young; Shin, Byung-Cheul; Ernst, Edzard

2012-01-01

This study aimed to assess the effectiveness of acupuncture as a treatment for autism spectrum disorders (ASD). We searched the literature using 15 databases. Eleven randomized clinical trials (RCTs) met our inclusion criteria. Most had significant methodological weaknesses. The studies' statistical and clinical heterogeneity prevented us from…

The efficacy of chiropractic manipulation for back pain : Blinded review of relevant randomized clinical trials

NARCIS (Netherlands)

Assendelft, W. J J; Koes, B. W.; Van der Heijden, G. J M G; Bouter, L. M.

1992-01-01

Objective: To assess the efficacy of chiropractic for patients with back pain. Data Sources: Randomized clinical trials (RCTs) on spinal manipulation were identified with a Medline search (1966-1990), by citation tracking, and by manual examination of the relevant chiropractic reference systems

Development of a framework to improve the process of recruitment to randomised controlled trials (RCTs): the SEAR (Screened, Eligible, Approached, Randomised) framework.

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Wilson, Caroline; Rooshenas, Leila; Paramasivan, Sangeetha; Elliott, Daisy; Jepson, Marcus; Strong, Sean; Birtle, Alison; Beard, David J; Halliday, Alison; Hamdy, Freddie C; Lewis, Rebecca; Metcalfe, Chris; Rogers, Chris A; Stein, Robert C; Blazeby, Jane M; Donovan, Jenny L

2018-01-19

Research has shown that recruitment to trials is a process that stretches from identifying potentially eligible patients, through eligibility assessment, to obtaining informed consent. The length and complexity of this pathway means that many patients do not have the opportunity to consider participation. This article presents the development of a simple framework to document, understand and improve the process of trial recruitment. Eight RCTs integrated a QuinteT Recruitment Intervention (QRI) into the main trial, feasibility or pilot study. Part of the QRI required mapping the patient recruitment pathway using trial-specific screening and recruitment logs. A content analysis compared the logs to identify aspects of the recruitment pathway and process that were useful in monitoring and improving recruitment. Findings were synthesised to develop an optimised simple framework that can be used in a wide range of RCTs. The eight trials recorded basic information about patients screened for trial participation and randomisation outcome. Three trials systematically recorded reasons why an individual was not enrolled in the trial, and further details why they were not eligible or approached, or declined randomisation. A framework to facilitate clearer recording of the recruitment process and reasons for non-participation was developed: SEAR - Screening, to identify potentially eligible trial participants; Eligibility, assessed against the trial protocol inclusion/exclusion criteria; Approach, the provision of oral and written information and invitation to participate in the trial, and Randomised or not, with the outcome of randomisation or treatment received. The SEAR framework encourages the collection of information to identify recruitment obstacles and facilitate improvements to the recruitment process. SEAR can be adapted to monitor recruitment to most RCTs, but is likely to add most value in trials where recruitment problems are anticipated or evident. Further work

Heterogenic control groups in randomized, controlled, analgesic trials of total hip and knee arthroplasty.

Science.gov (United States)

Karlsen, Anders P; Mathiesen, Ole; Dahl, Jørgen B

2018-03-01

Postoperative analgesic interventions are often tested adjunct to basic non-opioid analgesics in randomized controlled trials (RCTs). Consequently, treatment in control groups, and possible assay sensitivity, differs between trials. We hypothesized that postoperative opioid requirements and pain intensities vary between different control groups in analgesic trials. Control groups from RCTs investigating analgesic interventions after total hip and knee arthroplasty were categorized based on standardized basic analgesic treatment. Morphine consumption 0 to 24 hours postoperatively, and resting pain scores at 6 and 24 hours for subgroups of basic treatments, were compared with ANOVA. In an additional analysis, we compared pain and opioid requirements in trials where a non-steroidal anti-inflammatory drug (NSAID) was administered as an intervention with trial where NSAID was administered in a control group. We included 171 RCTs employing 28 different control groups with large variability in pain scores and opioid requirements. Four types of control groups (comprising 78 trials) were eligible for subgroup comparisons. These subgroups received "opioid" alone, "NSAID + opioid", "acetaminophen + opioid", or "NSAID + acetaminophen + opioid", respectively. Morphine consumption and pain scores varied substantially between these groups, with no consistent superior efficacy in any subgroup. Additionally, trials administering NSAID as an intervention demonstrated lower pain scores and opioid requirements than trials where NSAID was administered in a control group. Analgesic treatment in RCT control groups varies considerably. Control groups receiving various combinations of opioid, NSAID and acetaminophen did not differ consistently in pain and opioid requirements. Pain and opioid requirements were lower in trials administering NSAID as an intervention compared with trials administering NSAID in a control group.

Efficacy and safety of adjunctive topiramate for schizophrenia: a meta-analysis of randomized controlled trials.

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Zheng, W; Xiang, Y-T; Xiang, Y-Q; Li, X-B; Ungvari, G S; Chiu, H F K; Correll, C U

2016-11-01

To systematically examine the randomized controlled trial (RCT) evidence regarding efficacy and tolerability of topiramate cotreatment with antipsychotics in schizophrenia-spectrum disorders. Random-effects meta-analysis of RCTs of topiramate cotreatment with antipsychotics vs. placebo/ongoing antipsychotic treatment in schizophrenia-spectrum disorders. Standardized or weighted mean difference (SMD/WMD), risk ratio (RR) ±95% confidence intervals (CIs), and number needed to harm (NNH) were calculated. Across 16 RCTs (n = 934, duration = 11.8 ± 5.6 weeks), topiramate outperformed the comparator regarding change/endpoint of total (SMD: -0.58, 95% CI: -0.82, -0.35, P weight loss was greater in prevention/co-initiation vs. intervention/augmentation RCTs (-4.11 kg, 95% CI: -6.70, -1.52 vs. -1.41 kg, 95% CI: -2.23, -0.59, P schizophrenia-spectrum disorders. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Protocol for the development of a CONSORT-equity guideline to improve reporting of health equity in randomized trials.

Science.gov (United States)

Welch, Vivian; Jull, J; Petkovic, J; Armstrong, R; Boyer, Y; Cuervo, L G; Edwards, Sjl; Lydiatt, A; Gough, D; Grimshaw, J; Kristjansson, E; Mbuagbaw, L; McGowan, J; Moher, D; Pantoja, T; Petticrew, M; Pottie, K; Rader, T; Shea, B; Taljaard, M; Waters, E; Weijer, C; Wells, G A; White, H; Whitehead, M; Tugwell, P

2015-10-21

Health equity concerns the absence of avoidable and unfair differences in health. Randomized controlled trials (RCTs) can provide evidence about the impact of an intervention on health equity for specific disadvantaged populations or in general populations; this is important for equity-focused decision-making. Previous work has identified a lack of adequate reporting guidelines for assessing health equity in RCTs. The objective of this study is to develop guidelines to improve the reporting of health equity considerations in RCTs, as an extension of the Consolidated Standards of Reporting Trials (CONSORT). A six-phase study using integrated knowledge translation governed by a study executive and advisory board will assemble empirical evidence to inform the CONSORT-equity extension. To create the guideline, the following steps are proposed: (1) develop a conceptual framework for identifying "equity-relevant trials," (2) assess empirical evidence regarding reporting of equity-relevant trials, (3) consult with global methods and content experts on how to improve reporting of health equity in RCTs, (4) collect broad feedback and prioritize items needed to improve reporting of health equity in RCTs, (5) establish consensus on the CONSORT-equity extension: the guideline for equity-relevant trials, and (6) broadly disseminate and implement the CONSORT-equity extension. This work will be relevant to a broad range of RCTs addressing questions of effectiveness for strategies to improve practice and policy in the areas of social determinants of health, clinical care, health systems, public health, and international development, where health and/or access to health care is a primary outcome. The outcomes include a reporting guideline (CONSORT-equity extension) for equity-relevant RCTs and a knowledge translation strategy to broadly encourage its uptake and use by journal editors, authors, and funding agencies.

Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology.

Science.gov (United States)

Azar, Marleine; Riehm, Kira E; McKay, Dean; Thombs, Brett D

2015-01-01

Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals. Eligible RCTs were published in JCCP in 2013-2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration. Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709). The quality of published outcome analysis definitions and trial registrations in JCCP is

Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology.

Directory of Open Access Journals (Sweden)

Marleine Azar

Full Text Available Confidence that randomized controlled trial (RCT results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP is the primary trials journal amongst American Psychological Association (APA journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1 adequacy of primary outcome analysis definitions; (2 registration status; and, (3 among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals.Eligible RCTs were published in JCCP in 2013-2014. For each RCT, two investigators independently extracted data on (1 adequacy of outcome analysis definitions in the published report, (2 whether the RCT was registered prior to enrolling patients, and (3 adequacy of outcome registration.Of 70 RCTs reviewed, 12 (17.1% adequately defined primary or secondary outcome analyses, whereas 58 (82.3% had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7% registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029. The proportion of registered trials in JCCP (55.7% was comparable to behavioral medicine journals (52.6%; p = 0.709.The quality of published outcome analysis definitions and trial registrations in JCCP is

The conflict between randomized clinical trials and the therapeutic obligation.

Science.gov (United States)

Gifford, F

1986-11-01

The central dilemma concerning randomized clinical trials (RCTs) arises out of some simple facts about causal methodology (RCTs are the best way to generate the reliable causal knowledge necessary for optimally-informed action) and a prima facie plausible principle concerning how physicians should treat their patients (always do what it is most reasonable to believe will be best for the patient). A number of arguments related to this in the literature are considered. Attempts to avoid the dilemma fail. Appeals to informed consent and mechanisms for minimizing the resulting harm are important for policy, but informed consent is problematic and mechanisms for minimization of harm do not address the dilemma. Appeals to some sort of contract model of justification are promising and illuminating.

78 FR 63479 - Meta-Analyses of Randomized Controlled Clinical Trials (RCTs) for the Evaluation of Risk To...

Science.gov (United States)

2013-10-24

... pharmaceutical industry and health care organizations, and others from the general public, about the use of meta-analyses of randomized trials as a tool for safety assessment in the regulation of pharmaceutical products... PDUFA Goals Letter, titled ``Enhancing Regulatory Science and Expediting Drug Development,'' includes an...

Complementary and alternative medicine for rheumatic diseases: A systematic review of randomized controlled trials.

Science.gov (United States)

Phang, Jie Kie; Kwan, Yu Heng; Goh, Hendra; Tan, Victoria Ie Ching; Thumboo, Julian; Østbye, Truls; Fong, Warren

2018-04-01

To summarize all good quality randomized controlled trials (RCTs) using complementary and alternative medicine (CAM) interventions in patients with rheumatic diseases. A systematic literature review guided by the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) was performed. We excluded non-English language articles and abstract-only publications. Due to the large number of RCTs identified, we only include "good quality" RCTs with Jadad score of five. We identified 60 good quality RCTs using CAM as intervention for patients with rheumatic diseases: acupuncture (9), Ayurvedic treatment (3), homeopathic treatment (3), electricity (2), natural products (31), megavitamin therapies (8), chiropractic or osteopathic manipulation (3), and energy healing therapy (1). The studies do not seem to suggest a particular type of CAM is effective for all types for rheumatic diseases. However, some CAM interventions appear to be more effective for certain types of rheumatic diseases. Acupuncture appears to be beneficial for osteoarthritis but not rheumatoid arthritis. For the other therapeutic modalities, the evidence base either contains too few trials or contains trials with contradictory findings which preclude any definitive summary. There were only minor adverse reactions observed for CAM interventions presented. We identified 60 good quality RCTs which were heterogenous in terms of interventions, disease, measures used to assess outcomes, and efficacy of CAM interventions. Evidence indicates that some CAM therapies may be useful for rheumatic diseases, such as acupuncture for osteoarthritis. Further research with larger sample size is required for more conclusive evidence regarding efficacy of CAM interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Conduct and Reporting of Child Health Research: An Analysis of Randomized Controlled Trials Published in 2012 and Evaluation of Change over 5 Years.

Science.gov (United States)

Gates, Allison; Hartling, Lisa; Vandermeer, Ben; Caldwell, Patrina; Contopoulos-Ioannidis, Despina G; Curtis, Sarah; Fernandes, Ricardo M; Klassen, Terry P; Williams, Katrina; Dyson, Michele P

2018-02-01

For child health randomized controlled trials (RCTs) published in 2012, we aimed to describe design and reporting characteristics and evaluate changes since 2007; assess the association between trial design and registration and risk of bias (RoB); and assess the association between RoB and effect size. For 300 RCTs, we extracted design and reporting characteristics and assessed RoB. We assessed 5-year changes in design and reporting (based on 300 RCTs we had previously analyzed) using the Fisher exact test. We tested for associations between design and reporting characteristics and overall RoB and registration using the Fisher exact, Cochran-Armitage, Kruskal-Wallis, and Jonckheere-Terpstra tests. We pooled effect sizes and tested for differences by RoB using the χ 2 test for subgroups in meta-analysis. The 2012 and 2007 RCTs differed with respect to many design and reporting characteristics. From 2007 to 2012, RoB did not change for random sequence generation and improved for allocation concealment (P < .001). Fewer 2012 RCTs were rated high overall RoB and more were rated unclear (P = .03). Only 7.3% of 2012 RCTs were rated low overall RoB. Trial registration doubled from 2007 to 2012 (23% to 46%) (P < .001) and was associated with lower RoB (P = .009). Effect size did not differ by RoB (P = .43) CONCLUSIONS: Random sequence generation and allocation concealment were not often reported, and selective reporting was prevalent. Measures to increase trialists' awareness and application of existing reporting guidance, and the prospective registration of RCTs is needed to improve the trustworthiness of findings from this field. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Do authors report surgical expertise in open spine surgery related randomized controlled trials? A systematic review on quality of reporting

NARCIS (Netherlands)

van Oldenrijk, Jakob; van Berkel, Youri; Kerkhoffs, Gino M. M. J.; Bhandari, Mohit; Poolman, Rudolf W.

2013-01-01

A systematic review of published trials in orthopedic spine literature. To determine the quality of reporting in open spine surgery randomized controlled trials (RCTs) between 2005 and 2010 with special focus on the reporting of surgical skill or expertise. In technically demanding procedures such

An evaluation of the effectiveness of recruitment methods: the staying well after depression randomized controlled trial.

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Krusche, Adele; Rudolf von Rohr, Isabelle; Muse, Kate; Duggan, Danielle; Crane, Catherine; Williams, J Mark G

2014-04-01

Randomized controlled trials (RCTs) are widely accepted as being the most efficient way of investigating the efficacy of psychological therapies. However, researchers conducting RCTs commonly report difficulties in recruiting an adequate sample within planned timescales. In an effort to overcome recruitment difficulties, researchers often are forced to expand their recruitment criteria or extend the recruitment phase, thus increasing costs and delaying publication of results. Research investigating the effectiveness of recruitment strategies is limited, and trials often fail to report sufficient details about the recruitment sources and resources utilized. We examined the efficacy of strategies implemented during the Staying Well after Depression RCT in Oxford to recruit participants with a history of recurrent depression. We describe eight recruitment methods utilized and two further sources not initiated by the research team and examine their efficacy in terms of (1) the return, including the number of potential participants who contacted the trial and the number who were randomized into the trial; (2) cost-effectiveness, comprising direct financial cost and manpower for initial contacts and randomized participants; and (3) comparison of sociodemographic characteristics of individuals recruited from different sources. Poster advertising, web-based advertising, and mental health worker referrals were the cheapest methods per randomized participant; however, the ratio of randomized participants to initial contacts differed markedly per source. Advertising online, via posters, and on a local radio station were the most cost-effective recruitment methods for soliciting participants who subsequently were randomized into the trial. Advertising across many sources (saturation) was found to be important. It may not be feasible to employ all the recruitment methods used in this trial to obtain participation from other populations, such as those currently unwell, or in

Comparison of nuisance parameters in pediatric versus adult randomized trials: a meta-epidemiologic empirical evaluation

NARCIS (Netherlands)

Vandermeer, Ben; van der Tweel, Ingeborg; Jansen-van der Weide, Marijke C.; Weinreich, Stephanie S.; Contopoulos-Ioannidis, Despina G.; Bassler, Dirk; Fernandes, Ricardo M.; Askie, Lisa; Saloojee, Haroon; Baiardi, Paola; Ellenberg, Susan S.; van der Lee, Johanna H.

2018-01-01

Background: We wished to compare the nuisance parameters of pediatric vs. adult randomized-trials (RCTs) and determine if the latter can be used in sample size computations of the former. Methods: In this meta-epidemiologic empirical evaluation we examined meta-analyses from the Cochrane Database of

[Treatment of vascular dementia by Chinese herbal medicine: a systematic review of randomized controlled trials of clinical studies].

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Jian, Wen-Jia; Shi, Jing; Tian, Jin-Zhou; Ni, Jing-Nian

2015-01-01

Chinese herbal medicine has been extensively used in the treatment of vascular dementia (VaD), but lacked systematic review on its efficacy and safety. So we conducted a systematic review to assess the efficacy and safety of Chinese herbal medicine in treating VaD. CNKI, CBM, PubMed, and Wiley Online Library were retrieved for randomized trials (RCTs) on Chinese herbal medicine treating VaD patients. Randomized parallel control trials by taking Chinese herbal medicine as one treatment method and placebos/cholinesterase inhibitors/Memantine hydrochloride as the control were included. Quality rating and data extraction were performed. RevMan5.2.0 Software was used for meta-analysis. Standardized mean difference (SMD) at 95% confidence interval (CI) was used to indicate effect indicators of results. Seven RCTs met the inclusive criteria. Totally 677 VaD patients were randomly assigned to the treatment group and the control group. Descriptive analyses were performed in inclusive trials. The cognitive function was assessed in all trials. Results showed Mini-Mental state examination (MMSE) score was better in the Chinese herbal medicine group than in the placebo group, but with no significant difference when compared with the donepezil group (P > 0.05). Adverse reactions were mainly manifested as gastrointestinal symptoms such as abdominal pain in the Chinese herbal medicine group. But they occurred more in the donepezil group than in the Chinese herbal medicine group. The methodological quality of included trials was poor with less samples. Results of different trials were lack of consistency. Present evidence is not sufficient to prove or disapprove the role of Chinese herbal medicine in improving clinical symptoms and outcome indicators of VaD patients. Their clinical efficacy and safety need to be supported by more higher quality RCTs.

Patient Engagement in Randomized Controlled Tai Chi Clinical Trials among the Chronically Ill.

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Jiang, Dongsheng; Kong, Weihong; Jiang, Joanna J

2017-01-01

Physicians encounter various symptom-based complaints each day. While physicians strive to support patients with chronic illnesses, evidence indicates that patients who are actively involved in their health care have better health outcomes and sometimes lowers costs. This article is to analyze how patient engagement is described when complex interventions such as Tai Chi were delivered in Randomized Controlled clinical Trials (RCTs). It reviews the dynamic patient- physician relationship in chronic illness management and to illustrate the patient engagement process, using Tai Chi as an example intervention. RCTs are considered the gold standard in clinical research. This study is a qualitative analysis of RCTs using Tai Chi as an intervention. A systematic literature search was performed to identify quality randomized controlled clinical trials that investigated the effects of Tai Chi. Selected clinical trials were classified according to research design, intervention style, patient engagement, and outcomes. Patient engagement was classified based on levels of patient participation, compliance, and selfmanagement. The chronic health conditions included in this paper are Parkinson's disease, polyneuropathy, hypertension, stroke, chronic insomnia, chronic heart failure, fibromyalgia, osteoarthritis, central obesity, depression, deconditioning in the elderly, or being pre-clinically disabled. We found that patient engagement, as a concept, was not well defined in literature. It covers a wide range of related terms, such as patient involvement, participation, shared decision- making, patient activation, adherence, compliance, and self-management. Tai Chi, as a very complex practice system, is to balance all aspects of a patient's life; however, the level of patient engagement is difficult to describe using conventional clinical trial design. To accurately illustrate the effect of a complex intervention, novel research design must explore ways to measure patient

Systematic Review of Randomized Clinical Trials of Acupressure Therapy for Primary Dysmenorrhea

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Hui-ru Jiang

2013-01-01

Full Text Available The evidence of acupressure is limited in the management of dysmenorrhea. To evaluate the efficacy of acupressure in the treatment of primary dysmenorrhea based on randomized controlled trials (RCTs, we searched MEDLINE, the Chinese Biomedical Database (CBM, and the Cochrane Central Register of Controlled Trials (CENTRAL databases from inception until March 2012. Two reviewers independently selected articles and extracted data. Statistical analysis was performed with RevMan 5.1 software. Eight RCTs were identified from the retrieved 224 relevant records. Acupressure improved pain measured with VAS (−1.41 cm 95% CI [−1.61, −1.21], SF-MPQ at the 3-month followup (WMD −2.33, 95% CI [−4.11, −0.54] and 6-month followup (WMD −4.67, 95% CI [−7.30, −2.04], and MDQ at the 3-month followup (WMD −2.31, 95% CI [−3.74, −0.87] and 6-month followup (WMD −4.67, 95% CI [−7.30, −2.04]. All trials did not report adverse events. These results were limited by the methodological flaws of trials.

Chinese patent medicines for the treatment of the common cold: a systematic review of randomized clinical trials.

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Chen, Wei; Liu, Bo; Wang, Li-qiong; Ren, Jun; Liu, Jian-ping

2014-07-30

Many Chinese patent medicines (CPMs) have been authorized by the Chinese State of Food and Drug Administration for the treatment of the common cold. A number of clinical trials have been conducted and published. However, there is no systematic review or meta-analysis on their efficacy and safety for the common cold to justify their clinical use. We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites for published and unpublished randomized clinical trials (RCTs) of CPMs for the common cold till 31 March 2013. Revman 5.2 software was used for data analysis with effect estimate presented as relative risk (RR) and mean difference (MD) with a 95% confidence interval (CI). A total of five RCTs were identified. All of the RCTs were of high risk of bias with flawed study design and poor methodological quality. All RCTs included children aged between 6 months to 14 years. Results of individual trials showed that Shuanghuanglian oral liquid (RR 4.00; 95% CI: 2.26 to 7.08), and Xiaoer Resuqing oral liquid (RR 1.43; 95% CI: 1.15 to 1.77) had higher cure rates compared with antivirus drugs. Most of the trials did not report adverse events, and the safety of CPMs was still uncertain. Some CPMs showed a potential positive effect for the common cold on cure rate. However, due to the poor methodology quality and the defects in the clinical design of the included RCTs, such as the lack of placebo controlled trials, the inappropriate comparison intervention and outcome measurement, the confirmative conclusions on the beneficial effect of CPMs for the common cold could not be drawn.

Zinc intake and plasma/serum zinc concentration: a systematic review and meta-analysis of randomized controlled trials

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Warthon-Medina, M.; Dullemeijer, C.; Skinner, A.L.; Moran, V.H.

2011-01-01

A systematic review of randomized controlled trials (RCTs) was conducted to investigate how Zn intake influences plasma/serum Zn concentrations. We used protocols developed by EURRECA to perform a literature search for papers published up until February 2010 through MEDLINE, EMBASE, and Cochrane

A Proposed Multisite Double-Blind Randomized Clinical Trial of Neurofeedback for ADHD: Need, Rationale, and Strategy

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Kerson, Cynthia

2013-01-01

Objective: Additional treatments with persisting benefit are needed for ADHD. Because ADHD often shows excessive theta electroencephalogram (EEG) power, low beta, and excessive theta-beta ratio (TBR), a promising treatment is neurofeedback (NF) downtraining TBR. Although several nonblind randomized clinical trials (RCTs) show a medium-large…

[An investigation of the statistical power of the effect size in randomized controlled trials for the treatment of patients with type 2 diabetes mellitus using Chinese medicine].

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Ma, Li-Xin; Liu, Jian-Ping

2012-01-01

To investigate whether the power of the effect size was based on adequate sample size in randomized controlled trials (RCTs) for the treatment of patients with type 2 diabetes mellitus (T2DM) using Chinese medicine. China Knowledge Resource Integrated Database (CNKI), VIP Database for Chinese Technical Periodicals (VIP), Chinese Biomedical Database (CBM), and Wangfang Data were systematically recruited using terms like "Xiaoke" or diabetes, Chinese herbal medicine, patent medicine, traditional Chinese medicine, randomized, controlled, blinded, and placebo-controlled. Limitation was set on the intervention course > or = 3 months in order to identify the information of outcome assessement and the sample size. Data collection forms were made according to the checking lists found in the CONSORT statement. Independent double data extractions were performed on all included trials. The statistical power of the effects size for each RCT study was assessed using sample size calculation equations. (1) A total of 207 RCTs were included, including 111 superiority trials and 96 non-inferiority trials. (2) Among the 111 superiority trials, fasting plasma glucose (FPG) and glycosylated hemoglobin HbA1c (HbA1c) outcome measure were reported in 9% and 12% of the RCTs respectively with the sample size > 150 in each trial. For the outcome of HbA1c, only 10% of the RCTs had more than 80% power. For FPG, 23% of the RCTs had more than 80% power. (3) In the 96 non-inferiority trials, the outcomes FPG and HbA1c were reported as 31% and 36% respectively. These RCTs had a samples size > 150. For HbA1c only 36% of the RCTs had more than 80% power. For FPG, only 27% of the studies had more than 80% power. The sample size for statistical analysis was distressingly low and most RCTs did not achieve 80% power. In order to obtain a sufficient statistic power, it is recommended that clinical trials should establish clear research objective and hypothesis first, and choose scientific and evidence

Dropout Rates in Randomized Clinical Trials of Antipsychotics: A Meta-analysis Comparing First- and Second-Generation Drugs and an Examination of the Role of Trial Design Features

OpenAIRE

Rabinowitz, Jonathan; Levine, Stephen Z.; Barkai, Orna; Davidov, Ori

2008-01-01

Dropout is often used as an outcome measure in clinical trials of antipsychotic medication. Previous research is inconclusive regarding (a) differences in dropout rates between first- and second-generation antipsychotic medications and (b) how trial design features reduce dropout. Meta-analysis of randomized controlled trials (RCTs) of antipsychotic medication was conducted to compare dropout rates for first- and second-generation antipsychotic drugs and to examine how a broad range of design...

Randomized controlled trials in evidence-based mental health care: getting the right answer to the right question.

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Essock, Susan M; Drake, Robert E; Frank, Richard G; McGuire, Thomas G

2003-01-01

The purpose of clinical research is to answer this question: Would a new treatment, when added to the existing range of treatment options available in practice, help patients? Randomized controlled trials (RCTs)--in particular, double-blind RCTs--have important methodological advantages over observational studies for addressing this question. These advantages, however, come at a price. RCTs compare treatments using a particular allocation rule for assigning patients to treatments (random assignment) that does not mimic real-world practice. "Favorable" results from an RCT indicating that a new treatment is superior to existing treatments are neither necessary nor sufficient for establishing a "yes" answer to the question posed above. Modeled on an experimental design, RCTs are expensive in time and money and must compare simple differences in treatments. Findings have a high internal validity but may not address the needs of the field, particularly where treatment is complex and rapidly evolving. Design of clinical research needs to take account of the way treatments are allocated in actual practice and include flexible designs to answer important questions most effectively.

RANDOMIZED CONTROLLED TRIALS IN ORTHOPEDICS AND TRAUMATOLOGY: SYSTEMATIC ANALYSIS ON THE NATIONAL EVIDENCE

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de Moraes, Vinícius Ynoe; Moreira, Cesar Domingues; Tamaoki, Marcel Jun Sugawara; Faloppa, Flávio; Belloti, Joao Carlos

2015-01-01

Objective: To assess whether there has been any improvement in the quality and quantity of randomized controlled trials (RCTs) in nationally published journals through the application of standardized and validated scores. Methods: We electronically selected all RCTs published in the two indexed Brazilian journals that focus on orthopedics, over the period 2000-2009: Acta Ortopédica Brasileira (AOB) and Revista Brasileira de Ortopedia (RBO). These RCTs were identified and scored by two independent researchers in accordance with the Jadad scale and the Cochrane Bone, Joint and Muscle Trauma Group score. The studies selected were grouped as follows: 1) publication period (2000-2004 or 2004-2009); 2) journal of publication (AOB or RBO). Results: Twenty-two papers were selected: 10 from AOB and 12 from RBO. No statistically significant differences were found between the proportions (nRCT/nTotal of published papers) of RCTs published in the two journals (p = 0.458), or in the Jadad score (p = 0.722) and Cochrane score (p = 0.630). Conclusion: The relative quality and quantity of RCTs in the journals analyzed were similar. There was a trend towards improvement of quality, but there was no increase in the number of RCTs between the two periods analyzed. PMID:27026971

Systematic Review and Meta-Analysis of Randomized Controlled Trials of Xingnaojing Treatment for Stroke

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Weijun Peng

2014-01-01

Full Text Available Objective. Xingnaojing injection (XNJ is a well-known traditional Chinese patent medicine (TCPM for stroke. The aim of this study is to assess the efficacy of XNJ for stroke including ischemic stroke, intracerebral hemorrhage (ICH, and subarachnoid hemorrhage (SAH. Methods. An extensive search was performed within using eight databases up to November 2013. Randomized controlled trials (RCTs on XNJ for treatment of stroke were collected. Study selection, data extraction, quality assessment, and meta-analysis were conducted according to the Cochrane standards, and RevMan5.0 was used for meta-analysis. Results. This review included 13 RCTs and a total of 1,514 subjects. The overall methodological quality was poor. The meta-analysis showed that XNJ combined with conventional treatment was more effective for total efficacy, neurological deficit improvement, and reduction of TNF-α levels compared with those of conventional treatment alone. Three trials reported adverse events, of these one trial reported mild impairment of kidney and liver function, whereas the other two studies failed to report specific adverse events. Conclusion. Despite the limitations of this review, we suggest that XNJ in combination with conventional medicines might be beneficial for the treatment of stroke. Currently there are various methodological problems in the studies. Therefore, high-quality, large-scale RCTs are urgently needed.

Laparoscopic Anterior Versus Posterior Fundoplication for Gastroesophageal Reflux Disease Systematic Review and Meta-Analysis of Randomized Clinical Trials

NARCIS (Netherlands)

Broeders, Joris A.; Roks, David J.; Ahmed Ali, Usama; Draaisma, Werner A.; Smout, André J.; Hazebroek, Eric J.

2011-01-01

Objective: To compare short- and long-term outcome after laparoscopic anterior fundoplication (LAF) versus posterior fundoplication (LPF) through a systematic review and meta-analysis of randomized clinical trials (RCTs). Summary of Background Data: LPF is currently considered the surgical therapy

Barriers to participation in surgical randomized controlled trials in pediatric urology: A qualitative study of key stakeholder perspectives.

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Vemulakonda, Vijaya M; Jones, Jacqueline

2016-06-01

Randomized controlled trials (RCTs) are considered the gold standard for assessing treatment efficacy. However, pediatric surgical RCTs have been limited in their ability to recruit patients. The purpose of this study was to identify barriers and motivators to pediatric participation in surgical RCTs. We conducted a series of two focus groups with parents and one focus group with urology providers for children aged analysis of focus group findings. Theme analysis was used for all qualitative transcribed text data obtained from focus groups and open-ended survey questions using team-based inductive approaches. Descriptive statistics were obtained for the remainder of the provider survey. Using qualitative text from stakeholders (n = 38) we identified four key themes across the data: responsibility to my child; responsibility to my patient; responsibility to the field; and irreversibility of surgery. Participants felt there was an obligation to be informed of relevant scientific research within a clinic research culture. However, there remains a disconnect for parents between randomized research studies that may ultimately benefit their child, depending on their age and concern their child is being treated as a 'guinea pig'. Some parents were willing to participate in RCTs but all were more open to participate in an observational study where the treatment decisions were felt to be under their control even when there was no "right answer" or multiple equivalent options for treatment. There was mixed opinion across the parents and providers whether research trial education and enrollment should be provided by the pediatrician or urologist. Active physician decisions were seen as critical within the context of a long term clinical relationship and provision of information of risks and benefits without pressure were considered essential for ethical research by both parents and providers. While some parents are open to participation in surgical RCTs, providers and

Cultivating teacher mindfulness: Effects of a randomized controlled trial on work, home, and sleep outcomes.

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Crain, Tori L; Schonert-Reichl, Kimberly A; Roeser, Robert W

2017-04-01

The effects of randomization to a workplace mindfulness training (WMT) or a waitlist control condition on teachers' well-being (moods and satisfaction at work and home), quantity of sleep, quality of sleep, and sleepiness during the day were examined in 2 randomized, waitlist controlled trials (RCTs). The combined sample of the 2 RCTs, conducted in Canada and the United States, included 113 elementary and secondary school teachers (89% female). Measures were collected at baseline, postprogram, and 3-month follow-up; teachers were randomly assigned to condition after baseline assessment. Results showed that teachers randomized to WMT reported less frequent bad moods at work and home, greater satisfaction at work and home, more sleep on weekday nights, better quality sleep, and decreased insomnia symptoms and daytime sleepiness. Training-related group differences in mindfulness and rumination on work at home at postprogram partially mediated the reductions in negative moods at home and increases in sleep quality at follow-up. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Assessing Risk of Bias in Randomized Controlled Trials for Autism Spectrum Disorder

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Paola Matiko Martins Okuda

2017-11-01

Full Text Available AimTo determine construct validity and reliability indicators of the Cochrane risk of bias (RoB tool in the context of randomized clinical trials (RCTs for autism spectrum disorder (ASD.MethodsConfirmatory factor analysis was used to evaluate a unidimensional model consisting of 9 RoB categorical indicators evaluated across 94 RCTs addressing interventions for ASD.ResultsOnly five of the nine original RoB items returned good fit indices and so were retained in the analysis. Only one of this five had very high factor loadings. The remaining four indicators had more measurement error than common variance with the RoB latent factor. Together, the five indicators showed poor reliability (ω = 0.687; 95% CI: 0.613–0.761.ConclusionAlthough the Cochrane model of RoB for ASD exhibited good fit indices, the majorities of the items have more residual variance than common variance and, therefore, did not adequately capture the RoB in ASD intervention trials.

Methodological reporting of randomized controlled trials in major hepato-gastroenterology journals in 2008 and 1998: a comparative study

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2011-01-01

Background It was still unclear whether the methodological reporting quality of randomized controlled trials (RCTs) in major hepato-gastroenterology journals improved after the Consolidated Standards of Reporting Trials (CONSORT) Statement was revised in 2001. Methods RCTs in five major hepato-gastroenterology journals published in 1998 or 2008 were retrieved from MEDLINE using a high sensitivity search method and their reporting quality of methodological details were evaluated based on the CONSORT Statement and Cochrane Handbook for Systematic Reviews of interventions. Changes of the methodological reporting quality between 2008 and 1998 were calculated by risk ratios with 95% confidence intervals. Results A total of 107 RCTs published in 2008 and 99 RCTs published in 1998 were found. Compared to those in 1998, the proportion of RCTs that reported sequence generation (RR, 5.70; 95%CI 3.11-10.42), allocation concealment (RR, 4.08; 95%CI 2.25-7.39), sample size calculation (RR, 3.83; 95%CI 2.10-6.98), incomplete outecome data addressed (RR, 1.81; 95%CI, 1.03-3.17), intention-to-treat analyses (RR, 3.04; 95%CI 1.72-5.39) increased in 2008. Blinding and intent-to-treat analysis were reported better in multi-center trials than in single-center trials. The reporting of allocation concealment and blinding were better in industry-sponsored trials than in public-funded trials. Compared with historical studies, the methodological reporting quality improved with time. Conclusion Although the reporting of several important methodological aspects improved in 2008 compared with those published in 1998, which may indicate the researchers had increased awareness of and compliance with the revised CONSORT statement, some items were still reported badly. There is much room for future improvement. PMID:21801429

Assessing sample representativeness in randomized controlled trials: application to the National Institute of Drug Abuse Clinical Trials Network.

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Susukida, Ryoko; Crum, Rosa M; Stuart, Elizabeth A; Ebnesajjad, Cyrus; Mojtabai, Ramin

2016-07-01

To compare the characteristics of individuals participating in randomized controlled trials (RCTs) of treatments of substance use disorder (SUD) with individuals receiving treatment in usual care settings, and to provide a summary quantitative measure of differences between characteristics of these two groups of individuals using propensity score methods. Design Analyses using data from RCT samples from the National Institute of Drug Abuse Clinical Trials Network (CTN) and target populations of patients drawn from the Treatment Episodes Data Set-Admissions (TEDS-A). Settings Multiple clinical trial sites and nation-wide usual SUD treatment settings in the United States. A total of 3592 individuals from 10 CTN samples and 1 602 226 individuals selected from TEDS-A between 2001 and 2009. Measurements The propensity scores for enrolling in the RCTs were computed based on the following nine observable characteristics: sex, race/ethnicity, age, education, employment status, marital status, admission to treatment through criminal justice, intravenous drug use and the number of prior treatments. Findings The proportion of those with ≥ 12 years of education and the proportion of those who had full-time jobs were significantly higher among RCT samples than among target populations (in seven and nine trials, respectively, at P difference in the mean propensity scores between the RCTs and the target population was 1.54 standard deviations and was statistically significant at P different from individuals receiving treatment in usual care settings. Notably, RCT participants tend to have more years of education and a greater likelihood of full-time work compared with people receiving care in usual care settings. © 2016 Society for the Study of Addiction.

CPAP as treatment of sleep apnea after stroke: A meta-analysis of randomized trials.

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Brill, Anne-Kathrin; Horvath, Thomas; Seiler, Andrea; Camilo, Millene; Haynes, Alan G; Ott, Sebastian R; Egger, Matthias; Bassetti, Claudio L

2018-04-03

To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) examining the effectiveness of continuous positive airway pressure (CPAP) in stroke patients with sleep disordered breathing (SDB). In a systematic literature search of electronic databases (MEDLINE, Embase, and the Cochrane Library) from 1980 to November 2016, we identified RCTs that assessed CPAP compared to standard care or sham CPAP in adult patients with stroke or TIA with SDB. Mean CPAP use, odds ratios (ORs), and standardized mean differences (SMDs) were calculated. The prespecified outcomes were adherence to CPAP, neurologic improvement, adverse events, new vascular events, and death. Ten RCTs (564 participants) with CPAP as intervention were included. Two studies compared CPAP with sham CPAP; 8 compared CPAP with usual care. Mean CPAP use across the trials was 4.53 hours per night (95% confidence interval [CI] 3.97-5.08). The OR of dropping out with CPAP was 1.83 (95% CI 1.05-3.21, p = 0.033). The combined analysis of the neurofunctional scales (NIH Stroke Scale and Canadian Neurological Scale) showed an overall neurofunctional improvement with CPAP (SMD 0.5406, 95% CI 0.0263-1.0548) but with a considerable heterogeneity ( I 2 = 78.9%, p = 0.0394) across the studies. Long-term survival was improved with CPAP in 1 trial. CPAP use after stroke is acceptable once the treatment is tolerated. The data indicate that CPAP might be beneficial for neurologic recovery, which justifies larger RCTs. © 2018 American Academy of Neurology.

A systematic review of randomized controlled trials on curative and health enhancement effects of forest therapy

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Kamioka H

2012-07-01

Full Text Available Hiroharu Kamioka,1 Kiichiro Tsutani,2 Yoshiteru Mutoh,3 Takuya Honda,4 Nobuyoshi Shiozawa,5 Shinpei Okada,6 Sang-Jun Park,6 Jun Kitayuguchi,7 Masamitsu Kamada,8 Hiroyasu Okuizumi,9 Shuichi Handa91Faculty of Regional Environment Science, Tokyo University of Agriculture, Tokyo, 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 3Todai Policy Alternatives Research Institute, The University of Tokyo, Tokyo, 4Japanese Society for the Promotion of Science, Tokyo, 5Food Labeling Division, Consumer Affairs Agency, Cabinet Office, Government of Japan, Tokyo, 6Physical Education and Medicine Research Foundation, Nagano, 7Physical Education and Medicine Research Center Unnan, Shimane, 8Department of Environmental and Preventive Medicine, Shimane University School of Medicine, Shimane, 9Mimaki Onsen (Spa Clinic, Tomi City, Nagano, JapanObjective: To summarize the evidence for curative and health enhancement effects through forest therapy and to assess the quality of studies based on a review of randomized controlled trials (RCTs.Study design: A systematic review based on RCTs.Methods: Studies were eligible if they were RCTs. Studies included one treatment group in which forest therapy was applied. The following databases – from 1990 to November 9, 2010 – were searched: MEDLINE via PubMed, CINAHL, Web of Science, and Ichushi-Web. All Cochrane databases and Campbell Systematic Reviews were also searched up to November 9, 2010.Results: Two trials met all inclusion criteria. No specific diseases were evaluated, and both studies reported significant effectiveness in one or more outcomes for health enhancement. However, the results of evaluations with the CONSORT (Consolidated Standards of Reporting Trials 2010 and CLEAR NPT (A Checklist to Evaluate a Report of a Nonpharmacological Trial checklists generally showed a remarkable lack of description in the studies. Furthermore, there was a

Vitamin D and health: the need for more randomized controlled trials.

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Jorde, Rolf; Grimnes, Guri

2015-04-01

The importance of vitamin D for calcium absorption and bone health is undisputed. In addition, vitamin D may also be important for more than the skeleton as low serum levels of 25-hydroxyvitamin D (25(OH)D) have been associated with a number of diseases like cardiovascular disease, diabetes, cancer and infections. This is mainly based on observational studies and proof of causal relations from randomized controlled trials (RCTs) are lacking. At present several large RCTs including from 2152 to 25,000 subjects and with cardiovascular disease and cancer as endpoints are ongoing. Results are expected within 3-5 years, and hopefully these studies will give us a definite answer on need for vitamin D supplementation. However, since vitamin D deficiency (serum 25(OH)D vitamin D in truly vitamin D deficient subjects, studies that in retrospect obviously should have been the starting point for RCTs on vitamin D and health. This article is part of a Special Issue entitled '17th Vitamin D Workshop'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Randomized trials published in higher vs. lower impact journals differ in design, conduct, and analysis.

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Bala, Malgorzata M; Akl, Elie A; Sun, Xin; Bassler, Dirk; Mertz, Dominik; Mejza, Filip; Vandvik, Per Olav; Malaga, German; Johnston, Bradley C; Dahm, Philipp; Alonso-Coello, Pablo; Diaz-Granados, Natalia; Srinathan, Sadeesh K; Hassouneh, Basil; Briel, Matthias; Busse, Jason W; You, John J; Walter, Stephen D; Altman, Douglas G; Guyatt, Gordon H

2013-03-01

To compare methodological characteristics of randomized controlled trials (RCTs) published in higher vs. lower impact Core Clinical Journals. We searched MEDLINE for RCTs published in 2007 in Core Clinical Journals. We randomly sampled 1,140 study reports in a 1:1 ratio in higher (five general medicine journals with the highest total citations in 2007) and lower impact journals. Four hundred sixty-nine RCTs proved eligible: 219 in higher and 250 in lower impact journals. RCTs in higher vs. lower impact journals had larger sample sizes (median, 285 vs. 39), were more likely to receive industry funding (53% vs. 28%), declare concealment of allocation (66% vs. 36%), declare blinding of health care providers (53% vs. 41%) and outcome adjudicators (72% vs. 54%), report a patient-important primary outcome (69% vs. 50%), report subgroup analyses (64% vs. 26%), prespecify subgroup hypotheses (42% vs. 20%), and report a test for interaction (54% vs. 27%); P journals were more likely to report methodological safeguards against bias and patient-important outcomes than those published in lower impact journals. However, sufficient limitations remain such that publication in a higher impact journal does not ensure low risk of bias. Copyright © 2013 Elsevier Inc. All rights reserved.

Impact of the CONSORT Statement endorsement in the completeness of reporting of randomized clinical trials in restorative dentistry.

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Sarkis-Onofre, Rafael; Poletto-Neto, Victório; Cenci, Maximiliano Sérgio; Pereira-Cenci, Tatiana; Moher, David

2017-03-01

The aim of this study was to assess if journal endorsement of the CONSORT Statement is associated with improved completeness of reporting of randomized controlled trials (RCTs) in restorative dentistry. RCTs in restorative dentistry published in two journals that have (Journal of Dentistry and Clinical Oral Investigations) and have not (Operative Dentistry and Journal of Prosthetic Dentistry) endorsed the CONSORT Statement were selected. We compared the completeness of reporting between comparison groups (endorsers versus non-endorsers, before versus after endorsement) using a risk ratio (RR) with a 99% confidence interval for each outcome of CONSORT 2010. Also, the risk of bias of each study was evaluated. The electronic search retrieved a total of 3701 records. After the title and abstract evaluation, 169 full texts were screened and 79 RCTs identified. Considering CONSORT-endorsing journals before and after CONSORT endorsement, six items had effect estimates indicating a relatively higher proportion of completely reported RCTs published after CONSORT endorsement. Considering CONSORT-endorsing journals compared to non-endorsing journals, twelve items indicated a relatively higher proportion of completely reported RCTs published in CONSORT-endorsing journals. In both analyses the overall evidence did not present statistical significance. Although CONSORT endorsement has been linked with some improvement in the completeness of RCTs reports in the biomedical literature, this was not reflected in the present analysis confined to restorative dentistry. More innovative and involved approaches to enhancing reported may therefore be required. Inadequate reporting of randomized controlled trials can produce important consequences for all stakeholders including waste of resources and implication on healthcare decisions. A broad understandment of the use of reporting guidelines is necessary to lead to better results. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effectiveness of horticultural therapy: a systematic review of randomized controlled trials.

Science.gov (United States)

Kamioka, Hiroharu; Tsutani, Kiichiro; Yamada, Minoru; Park, Hyuntae; Okuizumi, Hiroyasu; Honda, Takuya; Okada, Shinpei; Park, Sang-Jun; Kitayuguchi, Jun; Abe, Takafumi; Handa, Shuichi; Mutoh, Yoshiteru

2014-10-01

To summarize the evidence from randomized controlled trials (RCTs) on the effects of horticultural therapy (HT). Studies were eligible if they were RCTs. Studies included one treatment group in which HT was applied. We searched the following databases from 1990 up to August 20, 2013: MEDLINE via PubMed, CINAHL, Web of Science, Ichushi-Web, GHL, WPRIM, and PsyclNFO. We also searched all Cochrane Database and Campbell Systematic Reviews up to September 20, 2013. Four studies met all inclusion criteria. The language of all eligible publications was English and Korean. Target diseases and/or symptoms were dementia, severe mental illness such as schizophrenia, bipolar disorder, and major depression, frail elderly in nursing home, and hemiplegic patients after stroke. These studies showed significant effectiveness in one or more outcomes for mental health and behavior. However, our review especially detected omissions of the following descriptions: method used to generate randomization, concealment, blinding, and intention-to-treat analysis. In addition, the results of this study suggested that the RCTs conducted have been of relatively low quality. Although there was insufficient evidence in the studies of HT due to poor methodological and reporting quality and heterogeneity, HT may be an effective treatment for mental and behavioral disorders such as dementia, schizophrenia, depression, and terminal-care for cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of perioperative insulin infusion on surgical morbidity and mortality: systematic review and meta-analysis of randomized trials.7

DEFF Research Database (Denmark)

Gandhi, G.Y.; Murad, M.H.; Flynn, D.N.

2008-01-01

OBJECTIVE: To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of perioperative insulin infusion on outcomes important to patients. PATIENTS AND METHODS: We used 6 search strategies including an electronic database search of MEDLINE, EMBA...

Adverse effects of homeopathy, what do we know? A systematic review and meta-analysis of randomized controlled trials.

Science.gov (United States)

Stub, Trine; Musial, Frauke; Kristoffersen, Agnete A; Alræk, Terje; Liu, Jianping

2016-06-01

Homeopathy is a popular treatment modality among patient, however there is sparse research about adverse effects of homeopathy. A concept unique for homeopathy, is homeopathic aggravation that is understood as a transient worsening of the patients' symptoms before an expected improvement occurs. From a risk perspective it is vital that a distinction between homeopathic aggravations and adverse effects is established. There is a lack of systematic information on how frequent adverse effects and homeopathic aggravations are reported in studies. Therefore, a systematic review and meta-analysis were performed. Sixteen electronic databases were searched for Randomized Controlled Trials (RCTs). The searches were limited from the year 1995 to January 2011. Forty-one RCTs, with a total of 6.055 participants were included. A subtotal of 39 studies was included in the additional meta-analysis. A total of 28 trials (68%) reported adverse effects and five trials (12%) reported homeopathic aggravations. The meta-analysis (including six subgroup comparisons) demonstrated that no significant difference was found between homeopathy and control with OR 0.99, 95% CI 0.86-1.14, I(2)=54%. More than two third of the adverse effects were classified as grade 1 (68%) and two third were classified as grade 2 (25%) and grade 3 (6%) according to the Common Terminology Criteria for Adverse Effects. Homeopathic aggravation was classified as grade 1 (98%) and grade 3 (2%), suggesting that homeopathic aggravations were reported to be less severe than adverse effects. The methodological quality according to a method recommended in the Cochrane handbook for RCTs, was high. Adverse effects including the concept of homeopathic aggravations are commonly reported in trials. The meta-analysis demonstrated that the proportion of patients experiencing adverse effects to be similar for patients randomized to homeopathic treatment compared to patients randomized to placebo and conventional medicine

Survivorship care plans: are randomized controlled trials assessing outcomes that are relevant to stakeholders?

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Birken, Sarah A; Urquhart, Robin; Munoz-Plaza, Corrine; Zizzi, Alexandra R; Haines, Emily; Stover, Angela; Mayer, Deborah K; Hahn, Erin E

2018-03-23

The purpose of this study was to compare outcomes assessed in extant randomized controlled trials (RCTs) to outcomes that stakeholders expect from survivorship care plans (SCPs). To facilitate the transition from active treatment to follow-up care for the 15.5 million US cancer survivors, many organizations require SCP use. However, results of several RCTs of SCPs' effectiveness have been null, possibly because they have evaluated outcomes on which SCPs should be expected to have limited influence. Stakeholders (e.g., survivors, oncologists) may expect outcomes that differ from RCTs' outcomes. We identified RCTs' outcomes using a PubMed literature review. We identified outcomes that stakeholders expect from SCPs using semistructured interviews with stakeholders in three healthcare systems in the USA and Canada. Finally, we mapped RCTs' outcomes onto stakeholder-identified outcomes. RCT outcomes did not fully address outcomes that stakeholders expected from SCPs, and RCTs assessed outcomes that stakeholders did not expect from SCPs. RCTs often assessed outcomes only from survivors' perspectives. RCTs of SCPs' effectiveness have not assessed outcomes that stakeholders expect. To better understand SCPs' effectiveness, future RCTs should assess outcomes of SCP use that are relevant from the perspective of multiple stakeholders. SCPs' effectiveness may be optimized when used with an eye toward outcomes that stakeholders expect from SCPs. For survivors, this means using SCPs as a map to guide them with respect to what kind of follow-up care they should seek, when they should seek it, and from whom they should seek it.

Proposed outcome measures for prospective clinical trials in juvenile idiopathic arthritis-associated uveitis

DEFF Research Database (Denmark)

Heiligenhaus, Arnd; Foeldvari, Ivan; Edelsten, Clive

2012-01-01

To develop a set of core outcome measures for use in randomized controlled trials (RCTs) and longitudinal observational studies in juvenile idiopathic arthritis (JIA)-associated uveitis.......To develop a set of core outcome measures for use in randomized controlled trials (RCTs) and longitudinal observational studies in juvenile idiopathic arthritis (JIA)-associated uveitis....

A Radical Sodium Reduction Policy is not Supported by Randomized Controlled Trials or Observational Studies

DEFF Research Database (Denmark)

Graudal, Niels

2016-01-01

Several health institutions recommend sodium intake be reduced to below 2,300 mg, which means that 6-7 billion individuals should alter their diet to accommodate. Such a radical recommendation should be based on solid evidence. However, this review reveals that (i) there are no randomized...... controlled trials (RCTs) allocating individuals to below 2,300 mg and measuring health outcomes; (ii) RCTs allocating risk groups such as obese prehypertensive individuals and hypertensive individuals down to (but not below) 2,300 mg show no effect of sodium reduction on all-cause mortality; (iii) RCTs...... allocating individuals to below 2,300 mg show a minimal effect on blood pressure in the healthy population (less than 1mm Hg) and significant increases in renin, aldosterone, noradrenalin cholesterol, and triglyceride; and (iv) observational studies show that sodium intakes below 2,645 and above 4,945 mg...

Probiotics for the management of neonatal hyperbilirubinemia: a systematic review of randomized controlled trials.

Science.gov (United States)

Deshmukh, Janki; Deshmukh, Mangesh; Patole, Sanjay

2017-08-31

Neonatal jaundice requiring phototherapy is associated with significant socioeconomic burden including hospital readmission, prolonged hospital stay, and separation of the baby from mother. To assess the efficacy and safety of probiotics in reducing the need for phototherapy and its duration in neonatal hyperbilirubinemia. A systematic review of randomized controlled trials (RCTs) of probiotic supplementation for prevention or treatment of jaundice in neonates (any gestation or weight) using the Cochrane methodology. Primary outcome was the duration of phototherapy. Secondary outcomes included incidence of jaundice, total serum bilirubin (TSB) level at 24, 48, 72, 96 h, and day 7, duration of hospital stay, and adverse effects (e.g. probiotic sepsis). Results were summarized as per GRADE guidelines. Nine RCTs (prophylactic: six trials, N = 1761; therapeutic: three trials, N = 279) with low to high risk of bias were included. Meta-analysis (random-effects model) showed probiotic supplementation reduced duration of phototherapy [N = 415, mean difference (MD): -11.80 (-17.47, -6.13); p probiotic treatment. Prophylactic probiotics did not reduce the incidence of jaundice significantly [N = 1582, relative risk (RR): 0.56 (0.25, 1.27); p = .16; LOE: low]. There were no probiotic-related adverse effects. Limited low-quality evidence indicates that probiotic supplementation may reduce the duration of phototherapy in neonates with jaundice. Routine use of probiotics to prevent or treat neonatal jaundice cannot be recommended. Large well-designed trials are essential to confirm these findings.

Cannabinoids for treatment of chronic non-cancer pain; a systematic review of randomized trials

OpenAIRE

Lynch, Mary E; Campbell, Fiona

2011-01-01

Effective therapeutic options for patients living with chronic pain are limited. The pain relieving effect of cannabinoids remains unclear. A systematic review of randomized controlled trials (RCTs) examining cannabinoids in the treatment of chronic non-cancer pain was conducted according to the PRISMA statement update on the QUORUM guidelines for reporting systematic reviews that evaluate health care interventions. Cannabinoids studied included smoked cannabis, oromucosal extracts of cannabi...

Effect of Risk of Bias on the Effect Size of Meta-Analytic Estimates in Randomized Controlled Trials in Periodontology and Implant Dentistry

Science.gov (United States)

Faggion, Clovis Mariano; Wu, Yun-Chun; Scheidgen, Moritz; Tu, Yu-Kang

2015-01-01

Background Risk of bias (ROB) may threaten the internal validity of a clinical trial by distorting the magnitude of treatment effect estimates, although some conflicting information on this assumption exists. Objective The objective of this study was evaluate the effect of ROB on the magnitude of treatment effect estimates in randomized controlled trials (RCTs) in periodontology and implant dentistry. Methods A search for Cochrane systematic reviews (SRs), including meta-analyses of RCTs published in periodontology and implant dentistry fields, was performed in the Cochrane Library in September 2014. Random-effect meta-analyses were performed by grouping RCTs with different levels of ROBs in three domains (sequence generation, allocation concealment, and blinding of outcome assessment). To increase power and precision, only SRs with meta-analyses including at least 10 RCTs were included. Meta-regression was performed to investigate the association between ROB characteristics and the magnitudes of intervention effects in the meta-analyses. Results Of the 24 initially screened SRs, 21 SRs were excluded because they did not include at least 10 RCTs in the meta-analyses. Three SRs (two from periodontology field) generated information for conducting 27 meta-analyses. Meta-regression did not reveal significant differences in the relationship of the ROB level with the size of treatment effect estimates, although a trend for inflated estimates was observed in domains with unclear ROBs. Conclusion In this sample of RCTs, high and (mainly) unclear risks of selection and detection biases did not seem to influence the size of treatment effect estimates, although several confounders might have influenced the strength of the association. PMID:26422698

Self-declared stock ownership and association with positive trial outcome in randomized controlled trials with binary outcomes published in general medical journals: a cross-sectional study.

Science.gov (United States)

Falk Delgado, Alberto; Falk Delgado, Anna

2017-07-26

Describe the prevalence and types of conflicts of interest (COI) in published randomized controlled trials (RCTs) in general medical journals with a binary primary outcome and assess the association between conflicts of interest and favorable outcome. Parallel-group RCTs with a binary primary outcome published in three general medical journals during 2013-2015 were identified. COI type, funding source, and outcome were extracted. Binomial logistic regression model was performed to assess association between COI and funding source with outcome. A total of 509 consecutive parallel-group RCTs were included in the study. COI was reported in 74% in mixed funded RCTs and in 99% in for-profit funded RCTs. Stock ownership was reported in none of the non-profit RCTs, in 7% of mixed funded RCTs, and in 50% of for-profit funded RCTs. Mixed-funded RCTs had employees from the funding company in 11% and for-profit RCTs in 76%. Multivariable logistic regression revealed that stock ownership in the funding company among any of the authors was associated with a favorable outcome (odds ratio = 3.53; 95% confidence interval = 1.59-7.86; p < 0.01). COI in for-profit funded RCTs is extensive, because the factors related to COI are not fully independent, a multivariable analysis should be cautiously interpreted. However, after multivariable adjustment only stock ownership from the funding company among authors is associated with a favorable outcome.

Expanding the Evidence Base: Comparing Randomized Controlled Trials and Observational Studies of Statins.

Science.gov (United States)

Atar, Dan; Ong, Seleen; Lansberg, Peter J

2015-01-01

It is widely accepted that randomized controlled trials (RCTs) are the gold standard for demonstrating the efficacy of a given therapy (results under ideal conditions). Observational studies, on the other hand, can complement this by demonstrating effectiveness (results under real-world conditions). To examine the role that observational studies can play in complementing data from RCTs, we reviewed published studies for statins, a class of drugs that have been widely used to reduce the risk of cardiovascular (CV) events by lowering low-density lipoprotein cholesterol levels. RCTs have consistently demonstrated the benefits of statin treatment in terms of CV risk reduction and have demonstrated that more intensive statin therapy has incremental benefits over less intensive treatment. Observational studies of statin use in 'real-world' populations have served to augment the evidence base generated from statin RCTs in preselected populations of patients who are often at high CV risk and have led to similar safety and efficacy findings. They have also raised questions about factors affecting medication adherence, under-treatment, switching between statins, and failure to reach low-density lipoprotein cholesterol target levels, questions for which the answers could lead to improved patient care.

Testing self-regulation interventions to increase walking using factorial randomized N-of-1 trials.

Science.gov (United States)

Sniehotta, Falko F; Presseau, Justin; Hobbs, Nicola; Araújo-Soares, Vera

2012-11-01

To investigate the suitability of N-of-1 randomized controlled trials (RCTs) as a means of testing the effectiveness of behavior change techniques based on self-regulation theory (goal setting and self-monitoring) for promoting walking in healthy adult volunteers. A series of N-of-1 RCTs in 10 normal and overweight adults ages 19-67 (M = 36.9 years). We randomly allocated 60 days within each individual to text message-prompted daily goal-setting and/or self-monitoring interventions in accordance with a 2 (step-count goal prompt vs. alternative goal prompt) × 2 (self-monitoring: open vs. blinded Omron-HJ-113-E pedometer) factorial design. Aggregated data were analyzed using random intercept multilevel models. Single cases were analyzed individually. The primary outcome was daily pedometer step counts over 60 days. Single-case analyses showed that 4 participants significantly increased walking: 2 on self-monitoring days and 2 on goal-setting days, compared with control days. Six participants did not benefit from the interventions. In aggregated analyses, mean step counts were higher on goal-setting days (8,499.9 vs. 7,956.3) and on self-monitoring days (8,630.3 vs. 7,825.9). Multilevel analyses showed a significant effect of the self-monitoring condition (p = .01), the goal-setting condition approached significance (p = .08), and there was a small linear increase in walking over time (p = .03). N-of-1 randomized trials are a suitable means to test behavioral interventions in individual participants.

Hypnosis in breast cancer care: a systematic review of randomized controlled trials.

Science.gov (United States)

Cramer, Holger; Lauche, Romy; Paul, Anna; Langhorst, Jost; Kümmel, Sherko; Dobos, Gustav J

2015-01-01

Many breast cancer patients and survivors experience pain and emotional stress related to their disease, its diagnostic procedures, or treatment. Hypnosis has long been used for the treatment of such symptoms. The aim of this review was to systematically assess the effectiveness of hypnosis in women with breast cancer, breast cancer survivors, and in women undergoing diagnostic breast biopsy. PubMed, Scopus, the Cochrane Library, PsycINFO, and CAMBASE were screened through February 2014 for randomized controlled trials (RCTs) of hypnosis in women with breast cancer or undergoing diagnostic breast biopsy. RCTs on postmenopausal women without a history of breast cancer were also eligible. Primary outcomes were pain, distress, fatigue, nausea/vomiting, and hot flashes. Safety was defined as secondary outcome measure. Risk of bias was assessed by 2 reviewers independently using the Cochrane Risk of Bias Tool. Thirteen RCTs with 1357 patients were included. In women undergoing diagnostic breast biopsy (3 RCTs), hypnosis positively influenced pain and distress; 1 RCT on breast cancer surgery found effects of hypnosis on pain, distress, fatigue, and nausea. For women undergoing radiotherapy (3 RCTs), hypnosis combined with cognitive-behavioral therapy improved distress and fatigue. In 3 RCTs on women with and without a history of breast cancer experiencing hot flashes, hypnosis improved hot flashes and distress. Three RCTs on women with metastatic breast cancer found effects on pain and distress. This systematic review found sparse but promising evidence for the effectiveness of hypnosis in breast cancer care. While more research is needed to underpin these results, hypnosis can be considered as an ancillary intervention in the management of breast cancer-related symptoms. © The Author(s) 2014.

The efficacy of laser therapy for musculoskeletal and skin disorders : A criteria-based meta-analysis of randomized clinical trials

NARCIS (Netherlands)

Beckerman, H.; De Bie, R. A.; Bouter, L. M.; De Cuyper, H. J.; Oostendorp, R. A.B.

1992-01-01

The efficacy of laser therapy for musculoskeletal and skin disorders has been assessed on the basis of the results of 36 randomized clinical trials (RCTs) involving 1,704 patients. For this purpose, a criteria-based meta- analysis that took into account the methodological quality of the individual

The quality of reporting of RCTs used within a postoperative pain management meta-analysis, using the CONSORT statement

Directory of Open Access Journals (Sweden)

Borg Debono Victoria

2012-07-01

Full Text Available Abstract Background Randomized controlled trials (RCTs are routinely used in systematic reviews and meta-analyses that help inform healthcare and policy decision making. The proper reporting of RCTs is important because it acts as a proxy for health care providers and researchers to appraise the quality of the methodology, conduct and analysis of an RCT. The aims of this study are to analyse the overall quality of reporting in 23 RCTs that were used in a meta-analysis by assessing 3 key methodological items, and to determine factors associated with high quality of reporting. It is hypothesized that studies with larger sample sizes, that have funding reported, that are published in journals with a higher impact factor and that are in journals that have adopted or endorsed the CONSORT statement will be associated with better overall quality of reporting and reporting of key methodological items. Methods We systematically reviewed RCTs used within an anesthesiology related post-operative pain management meta-analysis. We included all of the 23 RCTs used, all of which were parallel design that addressed the use of femoral nerve block in improving outcomes after total knee arthroplasty. Data abstraction was done independently by two reviewers. The two main outcomes were: 1 15 point overall quality of reporting score (OQRS based on the Consolidated Standards for Reporting Trials (CONSORT and 2 3 point key methodological item score (KMIS based on allocation concealment, blinding and intention-to-treat analysis. Results Twenty-three RCTs were included. The median OQRS was 9.0 (Interquartile Range = 3. A multivariable regression analysis did not show any significant association between OQRS or KMIS and our four predictor variables hypothesized to improve reporting. The direction and magnitude of our results when compared to similar studies suggest that the sample size and impact factor are associated with improved key methodological item reporting

Participant recruitment and retention in longitudinal preconception randomized trials: lessons learnt from the Calcium And Pre-eclampsia (CAP) trial.

Science.gov (United States)

Lawrie, Theresa A; Betrán, Ana Pilar; Singata-Madliki, Mandisa; Ciganda, Alvaro; Hofmeyr, G Justus; Belizán, José M; Purnat, Tina Dannemann; Manyame, Sarah; Parker, Catherine; Cormick, Gabriela

2017-10-26

The preconception period has the potential to influence pregnancy outcomes and randomized controlled trials (RCTs) are needed to evaluate a variety of potentially beneficial preconception interventions. However, RCTs commencing before pregnancy have significant participant recruitment and retention challenges. The Calcium And Pre-eclampsia trial (CAP trial) is a World Health Organization multi-country RCT of calcium supplementation commenced before pregnancy to prevent recurrent pre-eclampsia in which non-pregnant participants are recruited and followed up until childbirth. This sub-study explores recruitment methods and preconception retention of participants of the CAP trial to inform future trials. Recruiters at the study sites in Argentina, South Africa and Zimbabwe completed post-recruitment phase questionnaires on recruitment methods used. Qualitative data from these questionnaires and quantitative data on pre-pregnancy trial visit attendance and pregnancy rates up to September 2016 are reported in this paper. RStudio (Version 0.99.903 https://www.rstudio.org ) statistical software was used for summary statistics. Between July 2011 and 8 September 2016, 1354 women with previous pre-eclampsia were recruited. Recruitment took 2 years longer than expected and was facilitated mainly through medical record/register and maternity ward/clinic-based strategies. Recruiters highlighted difficulties associated with inadequate medical records, redundant patient contact details, and follow-up of temporarily ineligible women as some of the challenges faced. Whilst the attendance rates at pre-pregnancy visits were high (78% or more), visits often occurred later than scheduled. Forty-five percent of participants became pregnant (614/1354), 33.5% (454/1354) within 1 year of randomization. In preconception trials, both retrospective and prospective methods are useful for recruiting eligible women with certain conditions. However, these are time-consuming in low

An Assessment of the Risk of Bias in Randomized Controlled Trial Reports Published in Prosthodontic and Implant Dentistry Journals.

Science.gov (United States)

Papageorgiou, Spyridon N; Kloukos, Dimitrios; Petridis, Haralampos; Pandis, Nikolaos

2015-01-01

The objective of this study was to assess the risk of bias of randomized controlled trials (RCTs) published in prosthodontic and implant dentistry journals. The last 30 issues of 9 journals in the field of prosthodontic and implant dentistry (Clinical Implant Dentistry and Related Research, Clinical Oral Implants Research, Implant Dentistry, International Journal of Oral & Maxillofacial Implants, International Journal of Periodontics and Restorative Dentistry, International Journal of Prosthodontics, Journal of Dentistry, Journal of Oral Rehabilitation, and Journal of Prosthetic Dentistry) were hand-searched for RCTs. Risk of bias was assessed using the Cochrane Collaboration's risk of bias tool and analyzed descriptively. From the 3,667 articles screened, a total of 147 RCTs were identified and included. The number of published RCTs increased with time. The overall distribution of a high risk of bias assessment varied across the domains of the Cochrane risk of bias tool: 8% for random sequence generation, 18% for allocation concealment, 41% for masking, 47% for blinding of outcome assessment, 7% for incomplete outcome data, 12% for selective reporting, and 41% for other biases. The distribution of high risk of bias for RCTs published in the selected prosthodontic and implant dentistry journals varied among journals and ranged from 8% to 47%, which can be considered as substantial.

The effects of exercise on the quality of life of patients with breast cancer (the UMBRELLA Fit study) : study protocol for a randomized controlled trial

NARCIS (Netherlands)

Gal, Roxanne; Monninkhof, Evelyn M; Groenwold, Rolf H H; van Gils, Carla H; van den Bongard, Desiree H J G; Peeters, Petra H M; Verkooijen, Helena M; May, Anne M

2017-01-01

BACKGROUND: Meta-analyses of randomized controlled trials (RCTs) have shown that exercise has beneficial effects on quality of life (QoL) in patients with breast cancer. However, these effects were often small. Blinding in an exercise trial is not possible, which has the possible disadvantage of

Randomized clinical trials of dental bleaching - Compliance with the CONSORT Statement: a systematic review.

Science.gov (United States)

Loguercio, Alessandro Dourado; Maran, Bianca Medeiros; Hanzen, Taíse Alessandra; Paula, Alexandra Mara de; Perdigão, Jorge; Reis, Alessandra

2017-08-28

We reviewed the literature to evaluate: a) The compliance of randomized clinical trials (RCTs) on bleaching with the CONSORT; and b) the risk of bias of these studies using the Cochrane Collaboration risk of bias tool (CCRT). We searched the Cochrane Library, PubMed and other electronic databases, to find RCTs focused on bleaching (or whitening). The articles were evaluated in compliance with CONSORT in a scale: 0 = no description, 1 = poor description and 2 = adequate description. Descriptive analyses of the number of studies by journal, follow-up period, country and quality assessments were performed with CCRT for assessing risk of bias in RCTs. 185 RCTs were included for assessment. More than 30% of the studies received score 0 or 1. Protocol, flow chart, allocation concealment and sample size were more critical items, as 80% of the studies scored 0. The overall CONSORT score for the included studies was 16.7 ± 5.4 points, which represents 52.2% of the maximum CONSORT score. A significant difference among journal, country and period of time was observed (p risk; 62.1% were classified as "unclear"; and 30.3% as "high" risk of bias. The adherence of RCTs evaluating bleaching materials and techniques to the CONSORT is still low with unclear/high risk of bias.

Illness Management & Recovery (IMR) in the Netherlands : A naturalistic pilot study to explore the feasibility of a randomized controlled trial

NARCIS (Netherlands)

Roosenschoon, B.J.; Van Weeghel, J.; Bogaards, M.; Deen, M.L.; Mulder, C.L.

2016-01-01

Background Illness Management & Recovery (IMR) is a curriculum-based program for people with severe and persistent mental illness. To date, four randomized controlled trials (RCTs) have been published on it. As these produced mixed results, we conducted a pilot study to test the feasibility of

Illness Management & Recovery (IMR) in the Netherlands; a naturalistic pilot study to explore the feasibility of a randomized controlled trial

NARCIS (Netherlands)

B.J. Roosenschoon (Bert); J. van Weeghel (Jaap); Bogaards, M. (Moniek); M. Deen (Mathijs); C.L. Mulder (Niels)

2016-01-01

textabstractBackground: Illness Management & Recovery (IMR) is a curriculum-based program for people with severe and persistent mental illness. To date, four randomized controlled trials (RCTs) have been published on it. As these produced mixed results, we conducted a pilot study to test the

Evolution of Randomized Trials in Advanced/Metastatic Soft Tissue Sarcoma: End Point Selection, Surrogacy, and Quality of Reporting.

Science.gov (United States)

Zer, Alona; Prince, Rebecca M; Amir, Eitan; Abdul Razak, Albiruni

2016-05-01

Randomized controlled trials (RCTs) in soft tissue sarcoma (STS) have used varying end points. The surrogacy of intermediate end points, such as progression-free survival (PFS), response rate (RR), and 3-month and 6-month PFS (3moPFS and 6moPFS) with overall survival (OS), remains unknown. The quality of efficacy and toxicity reporting in these studies is also uncertain. A systematic review of systemic therapy RCTs in STS was performed. Surrogacy between intermediate end points and OS was explored using weighted linear regression for the hazard ratio for OS with the hazard ratio for PFS or the odds ratio for RR, 3moPFS, and 6moPFS. The quality of reporting for efficacy and toxicity was also evaluated. Fifty-two RCTs published between 1974 and 2014, comprising 9,762 patients, met the inclusion criteria. There were significant correlations between PFS and OS (R = 0.61) and between RR and OS (R = 0.51). Conversely, there were nonsignificant correlations between 3moPFS and 6moPFS with OS. A reduction in the use of RR as the primary end point was observed over time, favoring time-based events (P for trend = .02). In 14% of RCTs, the primary end point was not met, but the study was reported as being positive. Toxicity was comprehensively reported in 47% of RCTs, whereas 14% inadequately reported toxicity. In advanced STS, PFS and RR seem to be appropriate surrogates for OS. There is poor correlation between OS and both 3moPFS and 6moPFS. As such, caution is urged with the use of these as primary end points in randomized STS trials. The quality of toxicity reporting and interpretation of results is suboptimal. © 2016 by American Society of Clinical Oncology.

The reporting quality of randomized controlled trials in orthodontics.

Science.gov (United States)

Lempesi, Evangelia; Koletsi, Despina; Fleming, Padhraig S; Pandis, Nikolaos

2014-06-01

Accurate trial reporting facilitates evaluation and better use of study results. The objective of this article is to investigate the quality of reporting of randomized controlled trials (RCTs) in leading orthodontic journals, and to explore potential predictors of improved reporting. The 50 most recent issues of 4 leading orthodontic journals until November 2013 were electronically searched. Reporting quality assessment was conducted using the modified CONSORT statement checklist. The relationship between potential predictors and the modified CONSORT score was assessed using linear regression modeling. 128 RCTs were identified with a mean modified CONSORT score of 68.97% (SD = 11.09). The Journal of Orthodontics (JO) ranked first in terms of completeness of reporting (modified CONSORT score 76.21%, SD = 10.1), followed by American Journal of Orthodontics and Dentofacial Orthopedics (AJODO) (73.05%, SD = 10.1). Journal of publication (AJODO: β = 10.08, 95% CI: 5.78, 14.38; JO: β = 16.82, 95% CI: 11.70, 21.94; EJO: β = 7.21, 95% CI: 2.69, 11.72 compared to Angle), year of publication (β = 0.98, 95% CI: 0.28, 1.67 for each additional year), region of authorship (Europe: β = 5.19, 95% CI: 1.30, 9.09 compared to Asia/other), statistical significance (significant: β = 3.10, 95% CI: 0.11, 6.10 compared to non-significant) and methodologist involvement (involvement: β = 5.60, 95% CI: 1.66, 9.54 compared to non-involvement) were all significant predictors of improved modified CONSORT scores in the multivariable model. Additionally, median overall Jadad score was 2 (IQR = 2) across journals, with JO (median = 3, IQR = 1) and AJODO (median = 3, IQR = 2) presenting the highest score values. The reporting quality of RCTs published in leading orthodontic journals is considered suboptimal in various CONSORT areas. This may have a bearing in trial result interpretation and use in clinical decision making and evidence- based orthodontic treatment interventions. Copyright �

The blind leading the blind: use and misuse of blinding in randomized controlled trials.

Science.gov (United States)

Miller, Larry E; Stewart, Morgan E

2011-03-01

The use of blinding strengthens the credibility of randomized controlled trials (RCTs) by minimizing bias. However, there is confusion surrounding the definition of blinding as well as the terms single, double, and triple blind. It has been suggested that these terms should be discontinued due to their broad misinterpretation. We recommend that, instead of abandoning the use of these terms, explicit definitions of blinding should be adopted. We address herein the concept of blinding, propose standard definitions for the consistent use of these terms, and detail when different types of blinding should be utilized. Standardizing the definition of blinding and utilizing proper blinding methods will improve the quality and clarity of reporting in RCTs. Copyright © 2010 Elsevier Inc. All rights reserved.

Intention to treat (ITT) analysis as reported in orthodontic randomized controlled trials-evaluations of methodology and recommendations for the accurate use of ITT analysis and handling dropouts.

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Bondemark, Lars; Abdulraheem, Salem

2017-10-21

To systematically evaluate in five orthodontic journals how many randomized controlled trials (RCTs) use intention to treat (ITT) analysis and to assess the methodological quality of the ITT analysis, and finally, to demonstrate in an academic way how outcomes can be affected when not implementing the ITT analysis. A search of the database, Medline, was performed via PubMed for publication type 'randomized controlled trial' published for each journal between 1 January 2013 and 30 April 2017. The five orthodontic journals assessed were the American Journal of Orthodontics and Dentofacial Orthopedics, Angle Orthodontics, European Journal of Orthodontics, Journal of Orthodontics, and Orthodontics and Craniofacial Research. Two independent reviewers assessed each RCT to determine whether the trial reported an ITT or not or if a per-protocol analysis was accomplished. The initial search generated 137 possible trials. After applying the inclusion and exclusion criteria, 90 RCTs were included and assessed. Seventeen out of 90 RCTs (18.9%) either reported an ITT analysis in the text and/or supported the ITT by flow diagrams or tables. However, six RCTs applied and reported the ITT analysis correctly, while the majority performed a per-protocol analysis instead. Nearly all the trials that applied the ITT analysis incorrectly analysed the results using a per-protocol analysis, and thus, overestimating the results and/or having a reduced sample size which then could produce a diminished statistical power. © The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

"Open mesh" or "strictly selected population" recruitment? The experience of the randomized controlled MeMeMe trial.

Science.gov (United States)

Cortellini, Mauro; Berrino, Franco; Pasanisi, Patrizia

2017-01-01

Among randomized controlled trials (RCTs), trials for primary prevention require large samples and long follow-up to obtain a high-quality outcome; therefore the recruitment process and the drop-out rates largely dictate the adequacy of the results. We are conducting a Phase III trial on persons with metabolic syndrome to test the hypothesis that comprehensive lifestyle changes and/or metformin treatment prevents age-related chronic diseases (the MeMeMe trial, EudraCT number: 2012-005427-32, also registered on ClinicalTrials.gov [NCT02960711]). Here, we briefly analyze and discuss the reasons which may lead to participants dropping out from trials. In our experience, participants may back out of a trial for different reasons. Drug-induced side effects are certainly the most compelling reason. But what are the other reasons, relating to the participants' perception of the progress of the trial which led them to withdraw after randomization? What about the time-dependent drop-out rate in primary prevention trials? The primary outcome of this analysis is the point of drop-out from trial, defined as the time from the randomization date to the withdrawal date. Survival functions were non-parametrically estimated using the product-limit estimator. The curves were statistically compared using the log-rank test ( P =0.64, not significant). Researchers involved in primary prevention RCTs seem to have to deal with the paradox of the proverbial "short blanket syndrome". Recruiting only highly motivated candidates might be useful for the smooth progress of the trial but it may lead to a very low enrollment rate. On the other hand, what about enrolling all the eligible subjects without considering their motivation? This might boost the enrollment rate, but it can lead to biased results on account of large proportions of drop-outs. Our experience suggests that participants do not change their mind depending on the allocation group (intervention or control). There is no single

Lipid profile changes after pomegranate consumption: A systematic review and meta-analysis of randomized controlled trials.

Science.gov (United States)

Sahebkar, Amirhossein; Simental-Mendía, Luis E; Giorgini, Paolo; Ferri, Claudio; Grassi, Davide

2016-10-15

Transport of oxidized low-density lipoprotein across the endothelium into the artery wall is considered a fundamental priming step for the atherosclerotic process. Recent studies reported potential therapeutic effects of micronutrients found in natural products, indicating positive applications for controlling the pathogenesis of chronic cardiovascular disease driven by cardiovascular risk factors and oxidative stress. A particular attention has been recently addressed to pomegranate; however findings of clinical studies have been contrasting. To evaluate the effects of pomegranate consumption on plasma lipid concentrations through a systematic review and meta-analysis of randomized controlled trials (RCTs). The study was designed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. Scopus and Medline databases were searched to identify randomized placebo-controlled trials investigating the impact of pomegranate on plasma lipid concentrations. A fixed-effects model and the generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the one-study remove approach. Random-effects meta-regression was performed to assess the impact of potential confounders on the estimated effect sizes. A total of 545 individuals were recruited from the 12 RCTs. Fixed-effect meta-analysis of data from 12 RCTs (13 treatment arms) did not show any significant effect of pomegranate consumption on plasma lipid concentrations. The results of meta-regression did not suggest any significant association between duration of supplementation and impact of pomegranate on total cholesterol and HDL-C, while an inverse association was found with changes in triglycerides levels (slope: -1.07; 95% CI: -2.03 to -0.11; p = 0.029). There was no association between the amount of pomegranate juice consumed per day and respective changes in plasma total cholesterol, LDL-C, HDL-C and triglycerides. The

A Multisite Randomized Trial of a Cognitive Skills Program for Male Mentally Disordered Offenders: Violence and Antisocial Behavior Outcomes

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Cullen, Alexis E.; Clarke, Amory Y.; Kuipers, Elizabeth; Hodgins, Sheilagh; Dean, Kimberlie; Fahy, Tom

2012-01-01

Objective: Despite a large evidence base indicating that cognitive skills programs can reduce reoffending in individuals without mental illness, there have been no randomized controlled trials (RCTs) to determine their effectiveness in mentally disordered offenders (MDOs). In the first RCT of a cognitive skills program for MDOs, we aimed to…

Quality of randomized controlled trials published in the International Urogynecology Journal 2007-2016.

Science.gov (United States)

Kim, Kyu Shik; Chung, Jae Hoon; Jo, Jung Ki; Kim, Jae Heon; Kim, Seungjun; Cho, Jeoung Man; Cho, Hee Ju; Choi, Hong Yong; Lee, Seung Wook

2018-07-01

Randomized controlled trials (RCTs) provide the best quality clinical evidence. The aim of this study was to assess the quality of RCTs published by the International Urogynecology Journal (IUJ) in 2007-2016. RCTs in original articles were extracted from PubMed and IUJ homepage. Change in RCT quality over time was assessed with Jadad and van Tulder scales and Cochrane Collaboration's risk of bias tool (CCRBT). Jadad scores of 3-5 or van Tulder scores of >5 indicated high-quality RCTs. The effect on RCT quality of including funding source and institutional review board (IRB) approval statements and describing the intervention was assessed. In addition, changes in RCT topics over time were assessed. Annual RCT frequencies did not change significantly (6.7-15.7%): 36.1% and 25.7% described blinding and allocation concealment, respectively. Both tended to increase between 2013 and 2016, particularly 2013 and 2014. Funding statement inclusion (39.1% overall) and intervention description (78.2% overall) tended to increase steadily. IRB statement inclusion (60.4% overall) increased significantly (p < 0.01). Jadad scores and van Tulder rose significantly until 2014 (p < 0.01). Frequencies of high-quality RCTs tended to rise. CCRBT indicated that RCTs with a low risk of bias tended to increase until 2014. However, from 2015, Jadad scores, van Tulder, and CCRBT the low risk tended to decreased. RCTs with funding and IRB approval statements had higher Jadad and van Tulder scores than unfunded RCTs (p < 0.01 and p < 0.01, respectively). Intervention description did not associate with better quality. RCT quality improved over time, but a dip in quality was observed in 2015-2016 because of decreased blinding and allocation concealment.

Effect of sour tea (Hibiscus sabdariffa L.) on arterial hypertension: a systematic review and meta-analysis of randomized controlled trials.

Science.gov (United States)

Serban, Corina; Sahebkar, Amirhossein; Ursoniu, Sorin; Andrica, Florina; Banach, Maciej

2015-06-01

Hibiscus sabdariffa L. is a tropical wild plant rich in organic acids, polyphenols, anthocyanins, polysaccharides, and volatile constituents that are beneficial for the cardiovascular system. Hibiscus sabdariffa beverages are commonly consumed to treat arterial hypertension, yet the evidence from randomized controlled trials (RCTs) has not been fully conclusive. Therefore, we aimed to assess the potential antihypertensive effects of H. sabdariffa through systematic review of literature and meta-analysis of available RCTs. The search included PUBMED, Cochrane Library, Scopus, and EMBASE (up to July 2014) to identify RCTs investigating the efficacy of H. sabdariffa supplementation on SBP and DBP values. Two independent reviewers extracted data on the study characteristics, methods, and outcomes. Quantitative data synthesis and meta-regression were performed using a fixed-effect model, and sensitivity analysis using leave-one-out method. Five RCTs (comprising seven treatment arms) were selected for the meta-analysis. In total, 390 participants were randomized, of whom 225 were allocated to the H. sabdariffa supplementation group and 165 to the control group in the selected studies. Fixed-effect meta-regression indicated a significant effect of H. sabdariffa supplementation in lowering both SBP (weighed mean difference -7.58 mmHg, 95% confidence interval -9.69 to -5.46, P < 0.00001) and DBP (weighed mean difference -3.53 mmHg, 95% confidence interval -5.16 to -1.89, P < 0.0001). These effects were inversely associated with baseline BP values, and were robust in sensitivity analyses. This meta-analysis of RCTs showed a significant effect of H. sabdariffa in lowering both SBP and DBP. Further well designed trials are necessary to validate these results.

Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials.

Science.gov (United States)

Ha, Vanessa; Sievenpiper, John L; de Souza, Russell J; Jayalath, Viranda H; Mirrahimi, Arash; Agarwal, Arnav; Chiavaroli, Laura; Mejia, Sonia Blanco; Sacks, Frank M; Di Buono, Marco; Bernstein, Adam M; Leiter, Lawrence A; Kris-Etherton, Penny M; Vuksan, Vladimir; Bazinet, Richard P; Josse, Robert G; Beyene, Joseph; Kendall, Cyril W C; Jenkins, David J A

2014-05-13

Evidence from controlled trials encourages the intake of dietary pulses (beans, chickpeas, lentils and peas) as a method of improving dyslipidemia, but heart health guidelines have stopped short of ascribing specific benefits to this type of intervention or have graded the beneficial evidence as low. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction. We searched electronic databases and bibliographies of selected trials for relevant articles published through Feb. 5, 2014. We included RCTs of at least 3 weeks' duration that compared a diet emphasizing dietary pulse intake with an isocaloric diet that did not include dietary pulses. The lipid targets investigated were low-density lipoprotein (LDL) cholesterol, apolipoprotein B and non-high-density lipoprotein (non-HDL) cholesterol. We pooled data using a random-effects model. We identified 26 RCTs (n = 1037) that satisfied the inclusion criteria. Diets emphasizing dietary pulse intake at a median dose of 130 g/d (about 1 serving daily) significantly lowered LDL cholesterol levels compared with the control diets (mean difference -0.17 mmol/L, 95% confidence interval -0.25 to -0.09 mmol/L). Treatment effects on apolipoprotein B and non-HDL cholesterol were not observed. Our findings suggest that dietary pulse intake significantly reduces LDL cholesterol levels. Trials of longer duration and higher quality are needed to verify these results. ClinicalTrials.gov, no. NCT01594567.

Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized controlled trials.

Science.gov (United States)

Falagas, Matthew E; Vouloumanou, Evridiki K; Togias, Antonios G; Karadima, Maria; Kapaskelis, Anastasios M; Rafailidis, Petros I; Athanasiou, Stavros

2010-09-01

Cystitis is a common infection. The alarmingly high resistance rates exhibited by contemporary uropathogens necessitate the re-evaluation of old antibiotics. To evaluate the effectiveness and safety of fosfomycin compared with other antibiotics for the treatment of patients with cystitis. We performed a meta-analysis of randomized controlled trials (RCTs), generated from searches performed in PubMed, Scopus and Cochrane CENTRAL, which involved patients with cystitis treated with fosfomycin versus other antibiotics. Twenty-seven trials (eight double-blind) were included. Sixteen of these 27 trials involved exclusively non-pregnant female patients, 3 involved adult mixed populations of older age, 5 involved pregnant patients and 3 involved paediatric patients. Regarding clinical success, no difference was found in the comprehensive analysis regarding all comparators combined [10 RCTs, 1657 patients, risk ratio (RR) = 1.00, 95% confidence interval (CI) = 0.98-1.03] in trials involving non-pregnant females and in trials involving mixed populations. Insufficient relevant data were provided from trials involving paediatric and pregnant patients. No difference between fosfomycin and comparators was also found in all comparisons regarding the remaining effectiveness outcomes (namely microbiological success/relapse/re-infection). Fosfomycin had a comparable safety profile with the evaluated comparators in non-pregnant women, mixed and paediatric populations, whereas it was associated with significantly fewer adverse events in pregnant women (4 RCTs, 507 patients, RR = 0.35, 95% CI = 0.12-0.97). In the era of high drug resistance rates, reported even among community-acquired uropathogens, fosfomycin may provide a valuable alternative option for the treatment of cystitis in non-pregnant and pregnant women and in elderly and paediatric patients.

Electroconvulsive Therapy for Agitation in Schizophrenia: Metaanalysis of Randomized Controlled Trials.

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Gu, Xiaojing; Zheng, Wei; Guo, Tong; Ungvari, Gabor S; Chiu, Helen F K; Cao, Xiaolan; D'Arcy, Carl; Meng, Xiangfei; Ning, Yuping; Xiang, Yutao

2017-02-25

Agitation poses a significant challenge in the treatment of schizophrenia. Electroconvulsive therapy (ECT) is a fast, effective and safe treatment for a variety of psychiatric disorders, but no meta-analysis of ECT treatment for agitation in schizophrenia has yet been reported. To systematically evaluate the efficacy and safety of ECT alone or ECT-antipsychotics (APs) combination for agitation in schizophrenia. Systematic literature search of randomized controlled trials (RCTs) was performed. Two independent evaluators selected studies, extracted data about outcomes and safety with available data, conducted quality assessment and data synthesis. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to judge the level of the overall evidence of main outcomes. Seven RCTs from China, including ECT alone (4 RCTs with 5 treatment arms, n=240) and ECT-APs combination (3 RCTs, n=240), were identified. Participants in the studies were on average 34.3(4.5) years of age and lasted an average of 4.3(3.1) weeks of treatment duration. All 7 RCTs were non-blinded, and were rated as low quality based on Jadad scale. Meta-analysis of the pooled sample found no significant difference in the improvement of the agitation sub-score of the Positive and Negative Syndrome Scale (PANSS) when ECT alone (weighted mean difference=-0.90, (95% confidence interval (CI): -2.91, 1.11), p=0.38) or ECT-APs combination (WMD=-1.34, (95%CI: -4.07, 1.39), p=0.33) compared with APs monotherapy. However, ECT alone was superior to APs monotherapy regarding PANSS total score (WMD=-7.13, I 2 =0%, p =0.004) and its excitement sub-score (WMD=-1.97, p agitation related outcomes in schizophrenia patients. However, ECT alone or ECT-APs combination were associated with significant reduction in the PANSS total score. High-quality RCTs are needed to confirm the current interpretations.

Misuse of randomization

DEFF Research Database (Denmark)

Liu, Jianping; Kjaergard, Lise Lotte; Gluud, Christian

2002-01-01

The quality of randomization of Chinese randomized trials on herbal medicines for hepatitis B was assessed. Search strategy and inclusion criteria were based on the published protocol. One hundred and seventy-six randomized clinical trials (RCTs) involving 20,452 patients with chronic hepatitis B...... virus (HBV) infection were identified that tested Chinese medicinal herbs. They were published in 49 Chinese journals. Only 10% (18/176) of the studies reported the method by which they randomized patients. Only two reported allocation concealment and were considered as adequate. Twenty percent (30...

Insomnia From Drug Treatments: Evidence From Meta-analyses of Randomized Trials and Concordance With Prescribing Information.

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Doufas, Anthony G; Panagiotou, Orestis A; Panousis, Periklis; Wong, Shane Shucheng; Ioannidis, John P A

2017-01-01

To determine whether drugs used to treat diverse conditions cause insomnia symptoms and whether their prescription information is concordant with this evidence. We conducted a survey of meta-analyses (Cochrane Database of Systematic Reviews) and comparisons with package inserts compiled in the Physicians' Desk Reference (PDR). We identified randomized controlled trials (RCTs) in which any drug had been evaluated vs placebo and sleep had been assessed. We collectively referred to insomnia-related outcomes as sleep disturbance. We also searched the PDR to identify any insomnia symptoms listed for drugs with RCT evidence available. Seventy-four Cochrane systematic reviews corresponding to 274 RCTs assessed 88 drugs in 27 different conditions, providing evidence on 109 drug-condition pairs. Of these 88 drugs, 5 decreased sleep problems and 19 increased sleep problems; 64 drugs had no nominally statistically significant effect on sleep. Acetylcholinesterase inhibitors, dopamine agonists, and selective serotonin reuptake inhibitors were the drug classes most importantly associated with sleep disturbance. Of 35 drugs that included disturbed sleep as an adverse effect in the PDR, only 14 had RCT evidence supporting such effect, and 2 had evidence of increasing and decreasing sleep problems in RCTs, although this was not shown in the PDR. We identified weak concordance between the PDR and RCTs (weighted κ=0.31; P<.001). The RCTs offer substantial evidence about the common effects of drugs on the risk of sleep disturbance; currently, prescription information only partially agrees with the available randomized evidence. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Effectiveness of animal-assisted therapy: A systematic review of randomized controlled trials.

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Kamioka, Hiroharu; Okada, Shinpei; Tsutani, Kiichiro; Park, Hyuntae; Okuizumi, Hiroyasu; Handa, Shuichi; Oshio, Takuya; Park, Sang-Jun; Kitayuguchi, Jun; Abe, Takafumi; Honda, Takuya; Mutoh, Yoshiteru

2014-04-01

The objectives of this review were to summarize the evidence from randomized controlled trials (RCTs) on the effects of animal-assisted therapy (AAT). Studies were eligible if they were RCTs. Studies included one treatment group in which AAT was applied. We searched the following databases from 1990 up to October 31, 2012: MEDLINE via PubMed, CINAHL, Web of Science, Ichushi Web, GHL, WPRIM, and PsycINFO. We also searched all Cochrane Database up to October 31, 2012. Eleven RCTs were identified, and seven studies were about "Mental and behavioral disorders". Types of animal intervention were dog, cat, dolphin, bird, cow, rabbit, ferret, and guinea pig. The RCTs conducted have been of relatively low quality. We could not perform meta-analysis because of heterogeneity. In a study environment limited to the people who like animals, AAT may be an effective treatment for mental and behavioral disorders such as depression, schizophrenia, and alcohol/drug addictions, and is based on a holistic approach through interaction with animals in nature. To most effectively assess the potential benefits for AAT, it will be important for further research to utilize and describe (1) RCT methodology when appropriate, (2) reasons for non-participation, (3) intervention dose, (4) adverse effects and withdrawals, and (5) cost. Copyright © 2014 Elsevier Ltd. All rights reserved.

After the Gold Rush: Questioning the "Gold Standard" and Reappraising the Status of Experiment and Randomized Controlled Trials in Education

Science.gov (United States)

Thomas, Gary

2016-01-01

The past few years have seen a resurgence of faith in experimentation in education inquiry, and particularly in randomized controlled trials (RCTs). Proponents of such research have succeeded in bringing into common parlance the term "gold standard," which suggests that research emerging from any other design frame fails to achieve the…

Wet cupping therapy for treatment of herpes zoster: a systematic review of randomized controlled trials.

Science.gov (United States)

Cao, Huijuan; Zhu, Chenjun; Liu, Jianping

2010-01-01

Wet cupping is a traditional Chinese medicine therapy commonly used in treating herpes zoster in China, and clinical studies have shown that wet cupping may have beneficial effect on herpes zoster compared with Western medication. We included randomized controlled trials (RCTs) on wet cupping for herpes zoster. We searched PubMed, the Cochrane Library (Issue 3, 2008), China Network Knowledge Infrastructure (CNKI), Chinese Scientific Journals Fulltext Database VIP, and Wan Fang Database. All searches ended in February 2009. Two authors extracted data and assessed the trials' quality independently. RevMan 5.0.18 software (The Cochrane Collaboration, The Nordic Cochrane Centre, Copenhagen, Denmark) was used for data analysis with effect estimate presented as relative risk (RR) and mean difference (MD) with a 95% confidence interval (CI). Eight RCTs involving 651 patients were included, and the methodological quality of trials was generally fair in terms of randomization, blinding, and intention-to-treat analysis. Meta-analyses showed wet cupping was superior to medication in the number of cured patients (RR 2.49, 95% CI 1.91 to 3.24, P cupping plus medication was significantly better than medication alone on number of cured patients (RR 1.93, 95% CI 1.23 to 3.04, P = .005) but demonstrated no difference in symptom improvement (RR 1.00, 95% CI 0.92 to 1.08, P = .98). There were no serious adverse effects related to wet cupping therapy in the included trials. Wet cupping appears to be effective in the treatment of herpes zoster. However, further large, rigorously designed

Identifying Important Gaps in Randomized Controlled Trials of Adult Cardiac Arrest Treatments: A Systematic Review of the Published Literature

Science.gov (United States)

Sinha, Shashank S.; Sukul, Devraj; Lazarus, John J.; Polavarapu, Vivek; Chan, Paul S.; Neumar, Robert W.; Nallamothu, Brahmajee K.

2016-01-01

Background Cardiac arrests are a major public health concern worldwide. The extent and types of randomized controlled trials (RCTs) – our most reliable source of clinical evidence – conducted in these high-risk patients over recent years are largely unknown. Methods and Results We performed a systematic review, identifying all RCTs published in PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library from 1995 to 2014 that focused on acute treatment of non-traumatic cardiac arrest in adults. We then extracted data on the setting of study populations, types and timing of interventions studied, risk of bias, outcomes reported and how these factors have changed over time. Over this twenty-year period, 92 RCTs were published containing 64,309 patients (median, 225.5 per trial). Of these, 81 RCTs (88.0%) involved out-of-hospital cardiac arrest whereas 4 (4.3%) involved in-hospital cardiac arrest and 7 (7.6%) included both. Eighteen RCTs (19.6%) were performed in the U.S., 68 (73.9%) were performed outside the U.S., and 6 (6.5%) were performed in both settings. Thirty-eight RCTs (41.3%) evaluated drug therapy, 39 (42.4%) evaluated device therapy, and 15 (16.3%) evaluated protocol improvements. Seventy-four RCTs (80.4%) examined interventions during the cardiac arrest, 15 (16.3%) examined post-cardiac arrest treatment, and 3 (3.3%) studied both. Overall, reporting of risk of bias was limited. The most common outcome reported was ROSC: 86 (93.5%) with only 22 (23.9%) reporting survival beyond 6 months. Fifty-three RCTs (57.6%) reported global ordinal outcomes whereas 15 (16.3%) reported quality-of-life. RCTs in the last 5 years were more likely to be focused on protocol improvement and post-cardiac arrest care. Conclusions Important gaps in RCTs of cardiac arrest treatments exist, especially those examining in-hospital cardiac arrest, protocol improvement, post-cardiac arrest care, and long-term or quality-of-life outcomes. PMID:27756794

Impact of Cocoa Consumption on Inflammation Processes—A Critical Review of Randomized Controlled Trials

Science.gov (United States)

Ellinger, Sabine; Stehle, Peter

2016-01-01

Background: Cocoa flavanols have strong anti-inflammatory properties in vitro. If these also occur in vivo, cocoa consumption may contribute to the prevention or treatment of diseases mediated by chronic inflammation. This critical review judged the evidence for such effects occurring after cocoa consumption. Methods: A literature search in Medline was performed for randomized controlled trials (RCTs) that investigated the effects of cocoa consumption on inflammatory biomarkers. Results: Thirty-three RCTs were included, along with 9 bolus and 24 regular consumption studies. Acute cocoa consumption decreased adhesion molecules and 4-series leukotrienes in serum, nuclear factor κB activation in leukocytes, and the expression of CD62P and CD11b on monocytes and neutrophils. In healthy subjects and in patients with cardiovascular diseases, most regular consumption trials did not find any changes except for a decreased number of endothelial microparticles, but several cellular and humoral inflammation markers decreased in patients suffering from type 2 diabetes and impaired fasting glucose. Conclusions: Little evidence exists that consumption of cocoa-rich food may reduce inflammation, probably by lowering the activation of monocytes and neutrophils. The efficacy seems to depend on the extent of the basal inflammatory burden. Further well-designed RCTs with inflammation as the primary outcome are needed, focusing on specific markers of leukocyte activation and considering endothelial microparticles as marker of vascular inflammation. PMID:27240397

Impact of Cocoa Consumption on Inflammation Processes—A Critical Review of Randomized Controlled Trials

Directory of Open Access Journals (Sweden)

Sabine Ellinger

2016-05-01

Full Text Available Background: Cocoa flavanols have strong anti-inflammatory properties in vitro. If these also occur in vivo, cocoa consumption may contribute to the prevention or treatment of diseases mediated by chronic inflammation. This critical review judged the evidence for such effects occurring after cocoa consumption. Methods: A literature search in Medline was performed for randomized controlled trials (RCTs that investigated the effects of cocoa consumption on inflammatory biomarkers. Results: Thirty-three RCTs were included, along with 9 bolus and 24 regular consumption studies. Acute cocoa consumption decreased adhesion molecules and 4-series leukotrienes in serum, nuclear factor κB activation in leukocytes, and the expression of CD62P and CD11b on monocytes and neutrophils. In healthy subjects and in patients with cardiovascular diseases, most regular consumption trials did not find any changes except for a decreased number of endothelial microparticles, but several cellular and humoral inflammation markers decreased in patients suffering from type 2 diabetes and impaired fasting glucose. Conclusions: Little evidence exists that consumption of cocoa-rich food may reduce inflammation, probably by lowering the activation of monocytes and neutrophils. The efficacy seems to depend on the extent of the basal inflammatory burden. Further well-designed RCTs with inflammation as the primary outcome are needed, focusing on specific markers of leukocyte activation and considering endothelial microparticles as marker of vascular inflammation.

Impact of Cocoa Consumption on Inflammation Processes-A Critical Review of Randomized Controlled Trials.

Science.gov (United States)

Ellinger, Sabine; Stehle, Peter

2016-05-26

Cocoa flavanols have strong anti-inflammatory properties in vitro. If these also occur in vivo, cocoa consumption may contribute to the prevention or treatment of diseases mediated by chronic inflammation. This critical review judged the evidence for such effects occurring after cocoa consumption. A literature search in Medline was performed for randomized controlled trials (RCTs) that investigated the effects of cocoa consumption on inflammatory biomarkers. Thirty-three RCTs were included, along with 9 bolus and 24 regular consumption studies. Acute cocoa consumption decreased adhesion molecules and 4-series leukotrienes in serum, nuclear factor κB activation in leukocytes, and the expression of CD62P and CD11b on monocytes and neutrophils. In healthy subjects and in patients with cardiovascular diseases, most regular consumption trials did not find any changes except for a decreased number of endothelial microparticles, but several cellular and humoral inflammation markers decreased in patients suffering from type 2 diabetes and impaired fasting glucose. Little evidence exists that consumption of cocoa-rich food may reduce inflammation, probably by lowering the activation of monocytes and neutrophils. The efficacy seems to depend on the extent of the basal inflammatory burden. Further well-designed RCTs with inflammation as the primary outcome are needed, focusing on specific markers of leukocyte activation and considering endothelial microparticles as marker of vascular inflammation.

Efficacy of hydrotherapy in fibromyalgia syndrome--a meta-analysis of randomized controlled clinical trials.

Science.gov (United States)

Langhorst, Jost; Musial, Frauke; Klose, Petra; Häuser, Winfried

2009-09-01

To systematically review the efficacy of hydrotherapy in FM syndrome (FMS). We screened MEDLINE, PsychInfo, EMBASE, CAMBASE and CENTRAL (through December 2008) and the reference sections of original studies and systematic reviews on hydrotherapy in FMS. Randomized controlled trials (RCTs) on the treatment of FMS with hydrotherapy (spa-, balneo- and thalassotherapy, hydrotherapy and packing and compresses) were analysed. Methodological quality was assessed by the van Tulder score. Effects were summarized using standardized mean differences (SMDs). Ten out of 13 RCTs with 446 subjects, with a median sample size of 41 (range 24-80) and a median treatment time of 240 (range 200-300) min, were included into the meta-analysis. Only three studies had a moderate quality score. There was moderate evidence for reduction of pain (SMD -0.78; 95% CI -1.42, -0.13; P hydrotherapy has short-term beneficial effects on pain and HRQOL in FMS patients. There is a risk to over-estimate the effects of hydrotherapy due to methodological weaknesses of the studies and to small trials included in meta-analysis.

Sugars, obesity, and cardiovascular disease: results from recent randomized control trials.

Science.gov (United States)

Rippe, James M; Angelopoulos, Theodore J

2016-11-01

The relationship between sugar consumption and various health-related sequelas is controversial. Some investigators have argued that excessive sugar consumption is associated with increased risk of obesity, coronary heart disease, diabetes (T2D), metabolic syndrome, non-alcoholic fatty liver disease, and stimulation of reward pathways in the brain potentially causing excessive caloric consumption. These concerns have influenced organizations such as the World Health Organization, the Scientific Advisory Committee on Nutrition in England not to exceed 5 % of total energy and the Dietary Guidelines for Americans Advisory Committee 2015 to recommend upper limits of sugar consumption not to exceed 10 % of calories. Data from many randomized control trials (RCTs) do not support linkages between sugar consumption at normal levels within the human diet and various adverse metabolic and health-related effects. Fructose and glucose are typically consumed together in roughly equal proportions from high-fructose corn syrup (also known as isoglucose in Europe) or sucrose. The purpose of this review is to present data from recent RCTs and findings from recent systematic reviews and meta-analyses related to sugar consumption and its putative health effects. This review evaluates findings from recent randomized controlled trials, systematic reviews and meta-analyses into the relationship of sugar consumption and a range of health-related issues including energy-regulating hormones, obesity, cardiovascular disease, diabetes, and accumulation of liver fat and neurologic responses. Data from these sources do not support linkages between sugar consumption at normal levels within the human diet and various adverse metabolic and health-related effects.

Videogames and Health Improvement: A Literature Review of Randomized Controlled Trials.

Science.gov (United States)

Rahmani, Esmaeel; Boren, Suzanne Austin

2012-10-01

There are potential benefits of playing videogames for health improvement such as increasing knowledge about health-related issues by playing educational games and fighting a sedentary lifestyle by playing exergames. The number of systematic review articles about "videogames" and "health improvement" is limited. Therefore, the purpose of this study is to review those randomized controlled trials (RCTs) with the topic of "videogames" and "health improvement." Several electronic databases were searched for RCTs testing videogames on health outcomes that were published in English between January 2000 and April 2012. Forty-five articles met the eligibility criteria and were categorized into five groups: (1) videogames and patient pain and stress reduction (nine articles), (2) videogames and patient behavioral change (19 articles), (3) videogames and patient rehabilitation (eight articles), (4) videogames as diagnostic tools (three articles), and (5) videogames and cognitive ability (six articles). Most of the articles have shown promising results in using videogames within various fields of healthcare. Although exergames are the most prominent choice regarding health improvement, videogames have the potential to be used as a pain management tool, diagnostic tool, or educational tool. They also can be used as a facilitator in physical rehabilitation or cognitive loss prevention. More RCTs are needed to fully uncover the benefits of using videogames for improving patients' health.

Active implementation strategy of CONSORT adherence by a dental specialty journal improved randomized clinical trial reporting.

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Pandis, Nikolaos; Shamseer, Larissa; Kokich, Vincent G; Fleming, Padhraig S; Moher, David

2014-09-01

To describe a novel CONsolidated Standards of Reporting Trials (CONSORT) adherence strategy implemented by the American Journal of Orthodontics and Dentofacial Orthopedics (AJO-DO) and to report its impact on the completeness of reporting of published trials. The AJO-DO CONSORT adherence strategy, initiated in June 2011, involves active assessment of randomized clinical trial (RCT) reporting during the editorial process. The completeness of reporting CONSORT items was compared between trials submitted and published during the implementation period (July 2011 to September 2013) and trials published between August 2007 and July 2009. Of the 42 RCTs submitted (July 2011 to September 2013), 23 were considered for publication and assessed for completeness of reporting, seven of which were eventually published. For all published RCTs between 2007 and 2009 (n = 20), completeness of reporting by CONSORT item ranged from 0% to 100% (Median = 40%, interquartile range = 60%). All published trials in 2011-2013, reported 33 of 37 CONSORT (sub) items. Four CONSORT 2010 checklist items remained problematic even after implementation of the adherence strategy: changes to methods (3b), changes to outcomes (6b) after the trial commenced, interim analysis (7b), and trial stopping (14b), which are typically only reported when applicable. Trials published following implementation of the AJO-DO CONSORT adherence strategy completely reported more CONSORT items than those published or submitted previously. Copyright © 2014 Elsevier Inc. All rights reserved.

Ethical issues in pragmatic randomized controlled trials: a review of the recent literature identifies gaps in ethical argumentation.

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Goldstein, Cory E; Weijer, Charles; Brehaut, Jamie C; Fergusson, Dean A; Grimshaw, Jeremy M; Horn, Austin R; Taljaard, Monica

2018-02-27

Pragmatic randomized controlled trials (RCTs) are designed to evaluate the effectiveness of interventions in real-world clinical conditions. However, these studies raise ethical issues for researchers and regulators. Our objective is to identify a list of key ethical issues in pragmatic RCTs and highlight gaps in the ethics literature. We conducted a scoping review of articles addressing ethical aspects of pragmatic RCTs. After applying the search strategy and eligibility criteria, 36 articles were included and reviewed using content analysis. Our review identified four major themes: 1) the research-practice distinction; 2) the need for consent; 3) elements that must be disclosed in the consent process; and 4) appropriate oversight by research ethics committees. 1) Most authors reject the need for a research-practice distinction in pragmatic RCTs. They argue that the distinction rests on the presumptions that research participation offers patients less benefit and greater risk than clinical practice, but neither is true in the case of pragmatic RCTs. 2) Most authors further conclude that pragmatic RCTs may proceed without informed consent or with simplified consent procedures when risks are low and consent is infeasible. 3) Authors who endorse the need for consent assert that information need only be disclosed when research participation poses incremental risks compared to clinical practice. Authors disagree as to whether randomization must be disclosed. 4) Finally, all authors view regulatory oversight as burdensome and a practical impediment to the conduct of pragmatic RCTs, and argue that oversight procedures ought to be streamlined when risks to participants are low. The current ethical discussion is framed by the assumption that the function of research oversight is to protect participants from risk. As pragmatic RCTs commonly involve usual care interventions, the risks may be minimal. This leads many to reject the research-practice distinction and question

Does enteral nutrition affect clinical outcome? A systematic review of the randomized trials.

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Koretz, Ronald L; Avenell, Alison; Lipman, Timothy O; Braunschweig, Carol L; Milne, Anne C

2007-02-01

Both parenteral nutrition (PN) and enteral nutrition (EN) are widely advocated as adjunctive care in patients with various diseases. A systematic review of 82 randomized controlled trials (RCTs) of PN published in 2001 found little, if any, effect on mortality, morbidity, or duration of hospital stay; in some situations, PN increased infectious complication rates. The objective was to assess the effect of EN or volitional nutrition support (VNS) in individual disease states from available RCTs. We conducted a systematic review. RCTs comparing EN or VNS with untreated controls, or comparing EN with PN, were identified and separated according to the underlying disease state. Meta-analysis was performed when at least three RCTs provided data. The evidence from the RCTs was summarized into one of five grades. A or B, respectively, indicated the presence of strong or weak (low-quality RCTs) evidence supporting the use of the intervention. C indicated a lack of adequate evidence to make any decision about efficacy. D indicated that limited data could not support the intervention. E indicated either that strong data found no effect, or that either strong or weak data suggested that the intervention caused harm. RCTs could include either hospitalized or nonhospitalized patients. The EN or VNS had to be provided as part of a treatment plan for an underlying disease process. The RCT had to compare recipients of either EN or VNS with controls not receiving any type of artificial nutrition or had to compare recipients of EN with recipients of PN. These were mortality, morbidity (disease specific), duration of hospitalization, cost, or interventional complications. SUMMARY OF GRADING: A: No indication was identified. B: EN or VNS in the perioperative patient or in patients with chronic liver disease; EN in critically ill patients or low birth weight infants (trophic feeding); VNS in malnourished geriatric patients. (The low-quality trials found a significant difference in

How are palliative care cancer populations characterized in randomized controlled trials? A literature review.

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Sigurdardottir, Katrin Ruth; Oldervoll, Line; Hjermstad, Marianne Jensen; Kaasa, Stein; Knudsen, Anne Kari; Løhre, Erik Torbjørn; Loge, Jon Håvard; Haugen, Dagny Faksvåg

2014-05-01

The difficulties in defining a palliative care patient accentuate the need to provide stringent descriptions of the patient population in palliative care research. To conduct a systematic literature review with the aim of identifying which key variables have been used to describe adult palliative care cancer populations in randomized controlled trials (RCTs). The data sources used were MEDLINE (1950 to January 25, 2010) and Embase (1980 to January 25, 2010), limited to RCTs in adult cancer patients with incurable disease. Forty-three variables were systematically extracted from the eligible articles. The review includes 336 articles reporting RCTs in palliative care cancer patients. Age (98%), gender (90%), cancer diagnosis (89%), performance status (45%), and survival (45%) were the most frequently reported variables. A large number of other variables were much less frequently reported. A substantial variation exists in how palliative care cancer populations are described in RCTs. Few variables are consistently registered and reported. There is a clear need to standardize the reporting. The results from this work will serve as the basis for an international Delphi process with the aim of reaching consensus on a minimum set of descriptors to characterize a palliative care cancer population. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Conservative treatment of stress urinary incontinence in women: a systematic review of randomized clinical trials.

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Berghmans, L C; Hendriks, H J; Bo, K; Hay-Smith, E J; de Bie, R A; van Waalwijk van Doorn, E S

1998-08-01

To assess the efficacy of physical therapies for first-line use in the treatment and prevention of stress urinary incontinence (SUI) in women, using a systematic review of randomized clinical trials (RCTs). A computer-aided and manual search for published RCTs investigating treatment and prevention of SUI using physical therapies, e.g. pelvic floor muscle (PFM) exercises, with or without other treatment modalities, were carried out. The methodological quality of the included trials was assessed using criteria based on generally accepted principles of interventional research. Twenty-four RCTs (22 treatment and two prevention) were identified; the methodological quality of the studies included was moderate and 11 RCTs were of sufficient quality to be included in further analysis. Based on levels-of-evidence criteria, there is strong evidence to suggest that PFM exercises are effective in reducing the symptoms of SUI. There is limited evidence for the efficacy of high-intensity vs a low-intensity regimen of PFM exercises. Despite significant effects of biofeedback after testing as an adjunct to PFM exercises, there is no evidence that PFM exercises with biofeedback are more effective than PFM exercises alone. There is little consistency (of stimulation types and parameters) in the studies of electrical stimulation, but when the results are combined there is strong evidence to suggest that electrostimulation is superior to sham electrostimulation, and limited evidence that there is no difference between electrostimulation and other physical therapies. In the prevention of SUI the efficacy of PFM exercises, with or without other adjuncts, is uncertain.

What's in a Trial? On the Importance of Distinguishing Between Experimental Lab Studies and Randomized Controlled Trials: The Case of Cognitive Bias Modification and Alcohol Use Disorders.

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Wiers, Reinout W; Boffo, Marilisa; Field, Matt

2018-05-01

Recently, the National Institutes of Health (NIH) redefined clinical trials to include any study involving behavioral or biomedical interventions. In line with a general framework from experimental medicine, we argue that it is crucial to distinguish between experimental laboratory studies aimed at revealing psychological mechanisms underlying behavior and randomized controlled trials (RCTs) in clinical samples aimed at testing the efficacy of an intervention. As an illustration, we reviewed the current state of the evidence on the efficacy of cognitive bias modification (CBM) interventions in alcohol use disorders. A recent meta-analysis "cast serious doubts on the clinical utility of CBM interventions for addiction." That analysis combined experimental laboratory studies and RCTs. We demonstrated that, when studies are differentiated regarding study type (experimental laboratory study or RCT), mode of delivery (controlled experiment or Internet), and population (healthy volunteers or patients), the following effects are found: (a) short-lived effects of CBM on drinking behavior in experimental laboratory studies in students, but only when the bias is successfully manipulated; (b) small but robust effects of CBM on treatment outcome when administered as an adjunct to established treatments in clinical settings in RCTs with alcohol-dependent patients; and (c) nonspecific effects (reduced drinking irrespective of condition) in RCTs of CBM administered online to problem drinkers. We discuss how CBM might be improved when it is better integrated into regular treatment, especially cognitive behavioral therapy, and we conclude that disregarding the difference between experimental laboratory studies and RCTs can lead to invalid conclusions.

Sentence retrieval for abstracts of randomized controlled trials

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Chung Grace Y

2009-02-01

Full Text Available Abstract Background The practice of evidence-based medicine (EBM requires clinicians to integrate their expertise with the latest scientific research. But this is becoming increasingly difficult with the growing numbers of published articles. There is a clear need for better tools to improve clinician's ability to search the primary literature. Randomized clinical trials (RCTs are the most reliable source of evidence documenting the efficacy of treatment options. This paper describes the retrieval of key sentences from abstracts of RCTs as a step towards helping users find relevant facts about the experimental design of clinical studies. Method Using Conditional Random Fields (CRFs, a popular and successful method for natural language processing problems, sentences referring to Intervention, Participants and Outcome Measures are automatically categorized. This is done by extending a previous approach for labeling sentences in an abstract for general categories associated with scientific argumentation or rhetorical roles: Aim, Method, Results and Conclusion. Methods are tested on several corpora of RCT abstracts. First structured abstracts with headings specifically indicating Intervention, Participant and Outcome Measures are used. Also a manually annotated corpus of structured and unstructured abstracts is prepared for testing a classifier that identifies sentences belonging to each category. Results Using CRFs, sentences can be labeled for the four rhetorical roles with F-scores from 0.93–0.98. This outperforms the use of Support Vector Machines. Furthermore, sentences can be automatically labeled for Intervention, Participant and Outcome Measures, in unstructured and structured abstracts where the section headings do not specifically indicate these three topics. F-scores of up to 0.83 and 0.84 are obtained for Intervention and Outcome Measure sentences. Conclusion Results indicate that some of the methodological elements of RCTs are

Efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye: a systematic review of randomized clinical trials.

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Wu, Di; Chen, Wang Qi; Li, Ryan; Wang, Yan

2015-06-01

To evaluate the efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye. Randomized clinical trials (RCTs) from MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were identified to evaluate the efficacy and safety of topical administration of diquafosol to patients with dry eyes. Data evaluation was based on endpoints including Schirmer test, tear film break-up time, ocular surface staining score, subjective symptom score, and adverse events. A total of 8 RCTs involving 1516 patients were selected based on the prespecified criteria. Significant improvement of Schirmer test values and tear film break-up time were reported in 40% (2 of 5) and 80% (4 of 5) studies, respectively. Ocular surface staining scores significantly decreased in 100% (fluorescein corneal staining, 6 of 6; Rose Bengal corneal and conjunctival staining, 4 of 4) RCTs. Symptoms significantly improved in 75% (6 of 8) RCTs in patients with dry eyes. No severe adverse events were reported with the concentration of diquafosol from 0.5% to 5%. Heterogeneity in study design prevented meta-analysis from statistical integration and summarization. Topical diquafosol seems to be a safe therapeutic option for the treatment of dry eye. The high variability of the selected RCTs compromised the strength of evidence and limits the determination of efficacy. However, the topical administration of diquafosol seems to be beneficial in improving the integrity of the epithelial cell layer of the ocular surface and mucin secretion in patients with dry eyes. This review indicates a need for standardized criteria and methods for evaluation to assess the efficacy of diquafosol in the future clinical trials.

Patient advocacy and patient centredness in participant recruitment to randomized-controlled trials: implications for informed consent.

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Tomlin, Zelda; deSalis, Isabel; Toerien, Merran; Donovan, Jenny L

2014-10-01

With the routinization of evidence-based medicine and of the randomized-controlled trial (RCT), more patients are becoming 'sites of evidence production' yet, little is known about how they are recruited as participants; there is some evidence that 'substantively valid consent' is difficult to achieve. To explore the views and experiences of nurses recruiting patients to randomized-controlled trials and to examine the extent to which their recruitment practices were patient-centred and patient empowering. Semi-structured in-depth interviews; audio recording of recruitment appointments; thematic interactional analysis (drawing on discourse and conversation analysis). Nurses recruiting patients to five publicly funded RCTs and patients consenting to the recording of their recruitment sessions. The views of recruiting nurses about their recruitment role; the extent to which nurse-patient interactions were patient-centred; the nature of the nurses' interactional strategies and the nature and extent of patient participation in the discussion. The nurses had a keen sense of themselves as clinicians and patient advocates and their perceptions of the trial and its interventions were inextricably linked to those of the patients. However, many of their recruitment practices made it difficult for patients to play an active and informed part in the discussion about trial participation, raising questions over the quality of consent decisions. Nurses working in patient recruitment to RCTs need to reconcile two different worlds with different demands and ethics. Evidence production, a central task in evidence-based medicine, poses a challenge to patient-centred practice and more research and relevant training are needed. © 2012 John Wiley & Sons Ltd.

Measurement model choice influenced randomized controlled trial results.

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Gorter, Rosalie; Fox, Jean-Paul; Apeldoorn, Adri; Twisk, Jos

2016-11-01

In randomized controlled trials (RCTs), outcome variables are often patient-reported outcomes measured with questionnaires. Ideally, all available item information is used for score construction, which requires an item response theory (IRT) measurement model. However, in practice, the classical test theory measurement model (sum scores) is mostly used, and differences between response patterns leading to the same sum score are ignored. The enhanced differentiation between scores with IRT enables more precise estimation of individual trajectories over time and group effects. The objective of this study was to show the advantages of using IRT scores instead of sum scores when analyzing RCTs. Two studies are presented, a real-life RCT, and a simulation study. Both IRT and sum scores are used to measure the construct and are subsequently used as outcomes for effect calculation. The bias in RCT results is conditional on the measurement model that was used to construct the scores. A bias in estimated trend of around one standard deviation was found when sum scores were used, where IRT showed negligible bias. Accurate statistical inferences are made from an RCT study when using IRT to estimate construct measurements. The use of sum scores leads to incorrect RCT results. Copyright © 2016 Elsevier Inc. All rights reserved.

"Open mesh" or "strictly selected population" recruitment? The experience of the randomized controlled MeMeMe trial

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Cortellini M

2017-07-01

Full Text Available Mauro Cortellini, Franco Berrino, Patrizia Pasanisi Department of Preventive & Predictive Medicine, Foundation IRCCS National Cancer Institute of Milan, Milan, Italy Abstract: Among randomized controlled trials (RCTs, trials for primary prevention require large samples and long follow-up to obtain a high-quality outcome; therefore the recruitment process and the drop-out rates largely dictate the adequacy of the results. We are conducting a Phase III trial on persons with metabolic syndrome to test the hypothesis that comprehensive lifestyle changes and/or metformin treatment prevents age-related chronic diseases (the MeMeMe trial, EudraCT number: 2012-005427-32, also registered on ClinicalTrials.gov [NCT02960711]. Here, we briefly analyze and discuss the reasons which may lead to participants dropping out from trials. In our experience, participants may back out of a trial for different reasons. Drug-induced side effects are certainly the most compelling reason. But what are the other reasons, relating to the participants’ perception of the progress of the trial which led them to withdraw after randomization? What about the time-dependent drop-out rate in primary prevention trials? The primary outcome of this analysis is the point of drop-out from trial, defined as the time from the randomization date to the withdrawal date. Survival functions were non-parametrically estimated using the product-limit estimator. The curves were statistically compared using the log-rank test (P=0.64, not significant. Researchers involved in primary prevention RCTs seem to have to deal with the paradox of the proverbial “short blanket syndrome”. Recruiting only highly motivated candidates might be useful for the smooth progress of the trial but it may lead to a very low enrollment rate. On the other hand, what about enrolling all the eligible subjects without considering their motivation? This might boost the enrollment rate, but it can lead to biased

The effects of honey compared to silver sulfadiazine for the treatment of burns: A systematic review of randomized controlled trials.

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Aziz, Zoriah; Abdul Rasool Hassan, Bassam

2017-02-01

Evidence from animal studies and trials suggests that honey may accelerate wound healing. The objective of this review was to assess the effects of honey compared with silver dressings on the healing of burn wounds. Relevant databases for randomized controlled trials (RCTs) of honey compared with silver sulfadiazine (SSD) were searched. The quality of the selected trials was assessed using the Cochrane Risk of Bias Assessment Tool. The primary endpoints considered were wound healing time and the number of infected wounds rendered sterile. Nine RCTs met the inclusion criteria. Based on moderate quality evidence there was a statistically significant difference between the two groups, favoring honey in healing time (MD -5.76days, 95% CI -8.14 to -3.39) and the proportions of infected wounds rendered sterile (RR 2.59; 95% CI 1.58-2.88). The available evidence suggests that honey dressings promote better wound healing than silver sulfadiazine for burns. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Integrative treatment for low back pain: An exploratory systematic review and meta-analysis of randomized controlled trials.

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Hu, Xiao-Yang; Chen, Ni-Ni; Chai, Qian-Yun; Yang, Guo-Yan; Trevelyan, Esmé; Lorenc, Ava; Liu, Jian-Ping; Robinson, Nicola

2015-10-26

Low back pain (LBP) is a common musculoskeletal condition often treated using integrative medicine (IM). Most reviews have focused on a single complementary and alternative medicine (CAM) therapy for LBP rather than evaluating wider integrative approaches. This exploratory systematic review aimed to identify randomized controlled trials (RCTs) and provide evidence on the effectiveness, cost effectiveness and adverse effects of integrative treatment for LBP. A literature search was conducted in 12 English and Chinese databases. RCTs evaluating an integrative treatment for musculoskeletal related LBP were included. Reporting, methodological quality and relevant clinical characteristics were assessed and appraised. Metaanalyses were performed for outcomes where trials were sufficiently homogenous. Fifty-six RCTs were identified evaluating integrative treatment for LBP. Although reporting and methodological qualities were poor, meta-analysis showed a favourable effect for integrative treatment over conventional and CAM treatment for back pain and function at 3 months or less follow-up. Two trials investigated costs, reporting £ 5332 per quality adjusted life years with 6 Alexander technique lessons plus exercise at 12 months follow-up; and an increased total costs of $244 when giving an additional up to 15 sessions of CAM package of care at 12 weeks. Sixteen trials mentioned safety; no severe adverse effects were reported. Integrative treatment that combines CAM with conventional therapies appeared to have beneficial effects on pain and function. However, evidence is limited due to heterogeneity, the relatively small numbers available for subgroup analyses and the low methodological quality of the included trials. Identification of studies of true IM was not possible due to lack of reporting of the intervention details (registration No. CRD42013003916).

Blood pressure and endothelial function in healthy, pregnant women after acute and daily consumption of flavanol-rich chocolate: a pilot, randomized controlled trial

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2013-01-01

Background Several randomized clinical trials (RCTs) indicate that flavanol-rich chocolate has beneficial effects on flow-mediated dilation (FMD) and blood pressure (BP). However, no RCTs have evaluated these outcomes in pregnant women. The objective of this 2-group, parallel, double-blind RCT was to examine the effects of flavanol-rich chocolate on FMD and BP in pregnant women with normal BP. Methods Forty-four healthy, pregnant women were randomized to the high-flavanol (n = 23) or low-flavanol (n = 21) chocolate consumption for 12 weeks. At randomization (0, 60, 120 and 180 min after a single 40-g dose of chocolate), 6 and 12 weeks after daily 20-g chocolate intake, we evaluated plasma concentrations of flavanols and theobromine, as well as the FMD and BP. Results Plasma epicatechin was significantly increased (p chocolate compared to low-flavanol chocolate. Theobromine concentrations were significantly higher 180 min and 12 weeks after the intake of experimental chocolate or low-flavanol chocolate (p chocolate to an equivalent placebo during pregnancy and demonstrate higher plasma epicatechin and theobromine concentration in the intervention group after acute ingestion Trial registration ClinicalTrials.gov Identifier: NCT01659060 PMID:23565841

Moxibustion treatment for primary osteoporosis: A systematic review of randomized controlled trials.

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Fanping Xu

Full Text Available Primary osteoporosis (POP has a serious impact on quality of life for middle-aged and elderly, which particularly increase the risk of fracture. We conducted the systematic review to evaluate the effects of moxibustion for POP in randomized controlled trials (RCTs.Eight databases were searched from their inception to July 30, 2016. The RCTs reporting the moxibustion as a monotherapy or in combination with conventional therapy for POP were enrolled. The outcomes might be fracture incidence, quality of life, clinical symptoms, death attributed to osteoporosis, adverse effect, bone mineral density (BMD, and biochemical indicators. Literature selection, data abstraction, quality evaluation, and data analysis were in accordance with Cochrane standards.Thirteen trials including 808 patients were included. Meta-analysis was not conducted because of the obvious clinical or statistical heterogeneity. Limited evidence suggested that moxibustion plus anti-osteoporosis medicine might be more effective in relieving the pain (visual analogue scale scores average changed 2 scores between groups, 4 trials, increasing the BMD of femoral neck (average changed 0.4 g/cm2 between groups, 3 trials, and improving the level of bone gla protein, osteoprotegerin and bone alkaline phosphatase (2 trials compared with anti-osteoporosis medicine alone. However, the quality of previous studies was evaluated as generally poor. The safety evidence of moxibustion was still insufficient. Due to the paucity of high-quality studies, there was no definite conclusion about the efficacy and safety of moxibustion treating POP although parts of positive results were presented. Future research should pay attention to the dose-response relation and fracture incidence of moxibustion for POP.

Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review.

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Gaudry, Stéphane; Messika, Jonathan; Ricard, Jean-Damien; Guillo, Sylvie; Pasquet, Blandine; Dubief, Emeline; Boukertouta, Tanissia; Dreyfuss, Didier; Tubach, Florence

2017-12-01

Intensivists' clinical decision making pursues two main goals for patients: to decrease mortality and to improve quality of life and functional status in survivors. Patient-important outcomes are gaining wide acceptance in most fields of clinical research. We sought to systematically review how well patient-important outcomes are reported in published randomized controlled trials (RCTs) in critically ill patients. Literature search was conducted to identify eligible trials indexed from January to December 2013. Articles were eligible if they reported an RCT involving critically ill adult patients. We excluded phase II, pilot and physiological crossover studies. We assessed study characteristics. All primary and secondary outcomes were collected, described and classified using six categories of outcomes including patient-important outcomes (involving mortality at any time on the one hand and quality of life, functional/cognitive/neurological outcomes assessed after ICU discharge on the other). Of the 716 articles retrieved in 2013, 112 RCTs met the inclusion criteria. Most common topics were mechanical ventilation (27%), sepsis (19%) and nutrition (17%). Among the 112 primary outcomes, 27 (24%) were patient-important outcomes (mainly mortality, 21/27) but only six (5%) were patient-important outcomes besides mortality assessed after ICU discharge (functional disability = 4; quality of life = 2). Among the 598 secondary outcomes, 133 (22%) were patient-important outcomes (mainly mortality, 92/133) but only 41 (7%) were patient-important outcomes besides mortality assessed after ICU discharge (quality of life = 20, functional disability = 14; neurological/cognitive performance = 5; handicap = 1; post-traumatic stress = 1). Seventy-three RCTs (65%) reported at least one patient-important outcome but only 11 (10%) reported at least one patient-important outcome besides mortality assessed after ICU discharge. Patient-important outcomes are rarely primary

Potential misinterpretation of treatment effects due to use of odds ratios and logistic regression in randomized controlled trials.

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Mirjam J Knol

Full Text Available BACKGROUND: In randomized controlled trials (RCTs, the odds ratio (OR can substantially overestimate the risk ratio (RR if the incidence of the outcome is over 10%. This study determined the frequency of use of ORs, the frequency of overestimation of the OR as compared with its accompanying RR in published RCTs, and we assessed how often regression models that calculate RRs were used. METHODS: We included 288 RCTs published in 2008 in five major general medical journals (Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, New England Journal of Medicine. If an OR was reported, we calculated the corresponding RR, and we calculated the percentage of overestimation by using the formula . RESULTS: Of 193 RCTs with a dichotomous primary outcome, 24 (12.4% presented a crude and/or adjusted OR for the primary outcome. In five RCTs (2.6%, the OR differed more than 100% from its accompanying RR on the log scale. Forty-one of all included RCTs (n = 288; 14.2% presented ORs for other outcomes, or for subgroup analyses. Nineteen of these RCTs (6.6% had at least one OR that deviated more than 100% from its accompanying RR on the log scale. Of 53 RCTs that adjusted for baseline variables, 15 used logistic regression. Alternative methods to estimate RRs were only used in four RCTs. CONCLUSION: ORs and logistic regression are often used in RCTs and in many articles the OR did not approximate the RR. Although the authors did not explicitly misinterpret these ORs as RRs, misinterpretation by readers can seriously affect treatment decisions and policy making.

The quality of the reported sample size calculations in randomized controlled trials indexed in PubMed.

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Lee, Paul H; Tse, Andy C Y

2017-05-01

There are limited data on the quality of reporting of information essential for replication of the calculation as well as the accuracy of the sample size calculation. We examine the current quality of reporting of the sample size calculation in randomized controlled trials (RCTs) published in PubMed and to examine the variation in reporting across study design, study characteristics, and journal impact factor. We also reviewed the targeted sample size reported in trial registries. We reviewed and analyzed all RCTs published in December 2014 with journals indexed in PubMed. The 2014 Impact Factors for the journals were used as proxies for their quality. Of the 451 analyzed papers, 58.1% reported an a priori sample size calculation. Nearly all papers provided the level of significance (97.7%) and desired power (96.6%), and most of the papers reported the minimum clinically important effect size (73.3%). The median (inter-quartile range) of the percentage difference of the reported and calculated sample size calculation was 0.0% (IQR -4.6%;3.0%). The accuracy of the reported sample size was better for studies published in journals that endorsed the CONSORT statement and journals with an impact factor. A total of 98 papers had provided targeted sample size on trial registries and about two-third of these papers (n=62) reported sample size calculation, but only 25 (40.3%) had no discrepancy with the reported number in the trial registries. The reporting of the sample size calculation in RCTs published in PubMed-indexed journals and trial registries were poor. The CONSORT statement should be more widely endorsed. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Meta-analytic comparison of randomized and nonrandomized studies of breast cancer surgery.

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Edwards, Janet P; Kelly, Elizabeth J; Lin, Yongtao; Lenders, Taryn; Ghali, William A; Graham, Andrew J

2012-06-01

Randomized controlled trials (RCTs) are thought to provide the most accurate estimation of "true" treatment effect. The relative quality of effect estimates derived from nonrandomized studies (nRCTs) remains unclear, particularly in surgery, where the obstacles to performing high-quality RCTs are compounded. We performed a meta-analysis of effect estimates of RCTs comparing surgical procedures for breast cancer relative to those of corresponding nRCTs. English-language RCTs of breast cancer treatment in human patients published from 2003 to 2008 were identified in MEDLINE, EMBASE and Cochrane databases. We identified nRCTs using the National Library of Medicine's "related articles" function and reference lists. Two reviewers conducted all steps of study selection. We included studies comparing 2 surgical arms for the treatment of breast cancer. Information on treatment efficacy estimates, expressed as relative risk (RR) for outcomes of interest in both the RCTs and nRCTs was extracted. We identified 12 RCTs representing 10 topic/outcome combinations with comparable nRCTs. On visual inspection, 4 of 10 outcomes showed substantial differences in summary RR. The pooled RR estimates for RCTs versus nRCTs differed more than 2-fold in 2 of 10 outcomes and failed to demonstrate consistency of statistical differences in 3 of 10 cases. A statistically significant difference, as assessed by the z score, was not detected for any of the outcomes. Randomized controlled trials comparing surgical procedures for breast cancer may demonstrate clinically relevant differences in effect estimates in 20%-40% of cases relative to those generated by nRCTs, depending on which metric is used.

How Efficacious is Danshen (Salvia miltiorrhiza) Dripping Pill in Treating Angina Pectoris? Evidence Assessment for Meta-Analysis of Randomized Controlled Trials.

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Jia, Yongliang; Leung, Siu-Wai

2017-09-01

More than 230 randomized controlled trials (RCTs) of danshen dripping pill (DSP) and isosorbide dinitrate (ISDN) in treating angina pectoris after the first preferred reporting items for systematic reviews and meta-analyses-compliant comprehensive meta-analysis were published in 2010. Other meta-analyses had flaws in study selection, statistical meta-analysis, and evidence assessment. This study completed the meta-analysis with an extensive assessment of the evidence. RCTs published from 1994 to 2016 on DSP and ISDN in treating angina pectoris for at least 4 weeks were included. The risk of bias (RoB) of included RCTs was assessed with the Cochrane's tool for assessing RoB. Meta-analyses based on a random-effects model were performed on two outcome measures: symptomatic (SYM) and electrocardiography (ECG) improvements. Subgroup analysis, sensitivity analysis, metaregression, and publication bias analysis were also conducted. The evidence strength was evaluated with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) method. Among the included 109 RCTs with 11,973 participants, 49 RCTs and 5042 participants were new (after 2010). The RoB of included RCTs was high in randomization and blinding. Overall effect sizes in odds ratios for DSP over ISDN were 2.94 (95% confidence interval [CI]: 2.53-3.41) on SYM (n = 108) and 2.37 (95% CI: 2.08-2.69) by ECG (n = 81) with significant heterogeneities (I 2  = 41%, p < 0.0001 on SYM and I 2  = 44%, p < 0.0001 on ECG). Subgroup, sensitivity, and metaregression analyses showed consistent results without publication bias. However, the evidence strength was low in GRADE. The efficacy of DSP was still better than ISDN in treating angina pectoris, but the confidence decreased due to high RoB and heterogeneities.

N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials.

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Zheng, W; Zhang, Q-E; Cai, D-B; Yang, X-H; Qiu, Y; Ungvari, G S; Ng, C H; Berk, M; Ning, Y-P; Xiang, Y-T

2018-05-01

This systematic review and meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive N-acetylcysteine (NAC), an antioxidant drug, in treating major depressive disorder (MDD), bipolar disorder, and schizophrenia. The PubMed, Cochrane Library, PsycINFO, CNKI, CBM, and WanFang databases were independently searched and screened by two researchers. Standardized mean differences (SMDs), risk ratios, and their 95% confidence intervals (CIs) were computed. Six RCTs (n = 701) of NAC for schizophrenia (three RCTs, n = 307), bipolar disorder (two RCTs, n = 125), and MDD (one RCT, n = 269) were identified and analyzed as separate groups. Adjunctive NAC significantly improved total psychopathology (SMD = -0.74, 95% CI: -1.43, -0.06; I 2 = 84%, P = 0.03) in schizophrenia, but it had no significant effect on depressive and manic symptoms as assessed by the Young Mania Rating Scale in bipolar disorder and only a small effect on major depressive symptoms. Adverse drug reactions to NAC and discontinuation rates between the NAC and control groups were similar across the three disorders. Adjunctive NAC appears to be a safe treatment that has efficacy for schizophrenia, but not for bipolar disorder or MDD. Further higher quality RCTs are warranted to determine the role of adjunctive NAC in the treatment of major psychiatric disorders. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Are reports of randomized controlled trials improving over time? A systematic review of 284 articles published in high-impact general and specialized medical journals.

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To, Matthew J; Jones, Jennifer; Emara, Mohamed; Jadad, Alejandro R

2013-01-01

Inadequate reporting undermines findings of randomized controlled trials (RCTs). This study assessed and compared articles published in high-impact general medical and specialized journals. Reports of RCTs published in high-impact general and specialized medical journals were identified through a search of MEDLINE from January to March of 1995, 2000, 2005, and 2010. Articles that provided original data on adult patients diagnosed with chronic conditions were included in the study. Data on trial characteristics, reporting of allocation concealment, quality score, and the presence of a trial flow diagram were extracted independently by two reviewers, and discrepancies were resolved by consensus or independent adjudication. Descriptive statistics were used for quantitative variables. Comparisons between general medical and specialized journals, and trends over time were performed using Chi-square tests. Reports of 284 trials were analyzed. There was a significantly higher proportion of RCTs published with adequate reporting of allocation concealment (p = 0.003), presentation of a trial flow diagram (pgeneral medical journals had higher quality scores than those in specialized journals (p = 0.001), reported adequate allocation concealment more often (p = 0.013), and presented a trial flow diagram more often (pjournals over the last fifteen years. These improvements are likely attributed to concerted international efforts to improve reporting quality such as CONSORT. There is still much room for improvement, especially among specialized journals.

Efficacy and safety of tofacitinib for active rheumatoid arthritis with an inadequate response to methotrexate or disease-modifying antirheumatic drugs: a meta-analysis of randomized controlled trials

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Song, Gwan Gyu; Bae, Sang-Cheol

2014-01-01

Background/Aims The aim of this study was to assess the efficacy and safety of tofacitinib (5 and 10 mg twice daily) in patients with active rheumatoid arthritis (RA). Methods A systematic review of randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib in patients with active RA was performed using the Medline, Embase, and Cochrane Controlled Trials Register databases as well as manual searches. Results Five RCTs, including three phase-II and two phase-III trials involving 1,590 patients, met the inclusion criteria. The three phase-II RCTs included 452 patients with RA (144 patients randomized to 5 mg of tofacitinib twice daily, 156 patients randomized to 10 mg of tofacitinib twice daily, and 152 patients randomized to placebo) who were included in this meta-analysis. The American College of Rheumatology 20% response rate was significantly higher in the tofacitinib 5- and 10-mg groups than in the control group (relative risk [RR], 2.445; 95% confidence interval [CI], 1.229 to 4.861; p = 0.011; and RR, 2.597; 95% CI, 1.514 to 4.455; p = 0.001, respectively). The safety outcomes did not differ between the tofacitinib 5- and 10-mg groups and placebo groups with the exception of infection in the tofacitinib 10-mg group (RR, 2.133; 95% CI, 1.268 to 3.590; p = 0.004). The results of two phase-III trials (1,123 patients) confirmed the findings in the phase-II studies. Conclusions Tofacitinib at dosages of 5 and 10 mg twice daily was found to be effective in patients with active RA that inadequately responded to methotrexate or disease-modifying antirheumatic drugs, and showed a manageable safety profile. PMID:25228842

Conservative treatment of urge urinary incontinence in women: a systematic review of randomized clinical trials.

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Berghmans, L C; Hendriks, H J; De Bie, R A; van Waalwijk van Doorn, E S; Bø, K; van Kerrebroeck, P E

2000-02-01

To assess the efficacy of physical therapies for first-line use in the treatment of urge urinary incontinence (UUI) in women, using a systematic review of randomized clinical trials (RCTs). A computer-aided and manual search was carried out for RCTs published between 1980 and 1999 investigating the treatment of UUI defined by the keywords 'physical therapies', e.g. bladder (re)training (including 'behavioural' treatment), pelvic floor muscle (PFM) exercises, with or without biofeedback and/or electrical stimulation. The methodological quality of the included trials was assessed using methodological criteria, based on generally accepted principles of interventional research. Fifteen RCTs were identified; the methodological quality of the studies was moderate, with a median (range) score of 6 (3-8.5) (maximum possible 10). Eight RCTs were considered of sufficient quality, i.e. an internal validity score of >/= 5.5 points on a scale of 0-10, and were included in a further analysis. Based on levels-of-evidence criteria, there is weak evidence to suggest that bladder (re)training is more effective than no treatment (controls), and that bladder (re)training is better than drug therapy. Stimulation types and parameters in the studies of electrical stimulation were heterogeneous. There is insufficient evidence that electrical stimulation is more effective than sham electrical simulation. To date there are too few studies to evaluate effects of PFM exercise with or without biofeedback, and of toilet training for women with UUI. Although almost all studies included reported positive results in favour of physical therapies for the treatment of UUI, more research of high methodological quality is required to evaluate the effects of each method in the range of physical therapies.

Pilates Method for Women's Health: Systematic Review of Randomized Controlled Trials.

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Mazzarino, Melissa; Kerr, Debra; Wajswelner, Henry; Morris, Meg E

2015-12-01

To critically analyze the benefits of Pilates on health outcomes in women. CINAHL, MEDLINE, PubMed, Science Direct, SPORTDiscus, Physiotherapy Evidence Database (PEDro), Cochrane Central Register of Controlled Trials, and Web of Science. Databases were searched using the terms Pilates and Pilates Method. Published randomized controlled trials (RCTs) were included if they comprised female participants with a health condition and a health outcome was measured, Pilates needed to be administered, and the article was published in English in a peer-reviewed journal from 1980 to July 2014. Two authors independently applied the inclusion criteria to potential studies. Methodological quality was assessed using the PEDro scale. A best-evidence grading system was used to determine the strength of the evidence. Thirteen studies met the inclusion criteria. PEDro scale values ranged from 3 to 7 (mean, 4.5; median, 4.0), indicating a relatively low quality overall. In this sample, Pilates for breast cancer was most often trialed (n=2). The most frequent health outcomes investigated were pain (n=4), quality of life (n=4), and lower extremity endurance (n=2), with mixed results. Emerging evidence was found for reducing pain and improving quality of life and lower extremity endurance. There is a paucity of evidence on Pilates for improving women's health during pregnancy or for conditions including breast cancer, obesity, or low back pain. Further high-quality RCTs are warranted to determine the effectiveness of Pilates for improving women's health outcomes. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Short and long-term safety and efficacy of polymer-free vs. durable polymer drug-eluting stents. A comprehensive meta-analysis of randomized trials including 6178 patients

NARCIS (Netherlands)

Navarese, E.P.; Kowalewski, M.; Cortese, B.; Kandzari, D.; Dias, S.; Wojakowski, W.; Buffon, A.; Lansky, A.; Angelini, P.; Torguson, R.; Kubica, J.; Kelm, M.; Boer, M.J. de; Waksman, R.; Suryapranata, H.

2014-01-01

BACKGROUND: The efficacy and safety of polymer-free drug-eluting stents (DESs) in clinical practice is currently subject of debate; randomized trials (RCTs) conducted so far provided conflicting results or were underpowered to definitively address this question; we aimed to investigate the efficacy

Randomized clinical trials of dental bleaching – Compliance with the CONSORT Statement: a systematic review

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Alessandro Dourado LOGUERCIO

2017-08-01

Full Text Available Abstract We reviewed the literature to evaluate: a The compliance of randomized clinical trials (RCTs on bleaching with the CONSORT; and b the risk of bias of these studies using the Cochrane Collaboration risk of bias tool (CCRT. We searched the Cochrane Library, PubMed and other electronic databases, to find RCTs focused on bleaching (or whitening. The articles were evaluated in compliance with CONSORT in a scale: 0 = no description, 1 = poor description and 2 = adequate description. Descriptive analyses of the number of studies by journal, follow-up period, country and quality assessments were performed with CCRT for assessing risk of bias in RCTs. 185 RCTs were included for assessment. More than 30% of the studies received score 0 or 1. Protocol, flow chart, allocation concealment and sample size were more critical items, as 80% of the studies scored 0. The overall CONSORT score for the included studies was 16.7 ± 5.4 points, which represents 52.2% of the maximum CONSORT score. A significant difference among journal, country and period of time was observed (p < 0.02. Only 7.6% of the studies were judged at “low” risk; 62.1% were classified as “unclear”; and 30.3% as “high” risk of bias. The adherence of RCTs evaluating bleaching materials and techniques to the CONSORT is still low with unclear/high risk of bias.

Development and evaluation of an Individualized Outcome Measure (IOM) for randomized controlled trials in mental health.

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Pesola, Francesca; Williams, Julie; Bird, Victoria; Freidl, Marion; Le Boutillier, Clair; Leamy, Mary; Macpherson, Rob; Slade, Mike

2015-12-01

Pre-defined, researcher-selected outcomes are routinely used as the clinical end-point in randomized controlled trials (RCTs); however, individualized approaches may be an effective way to assess outcome in mental health research. The present study describes the development and evaluation of the Individualized Outcome Measure (IOM), which is a patient-specific outcome measure to be used for RCTs of complex interventions. IOM was developed using a narrative review, expert consultation and piloting with mental health service users (n = 20). The final version of IOM comprises two components: Goal Attainment (GA) and Personalized Primary Outcome (PPO). For GA, patients identify one relevant goal at baseline and rate its attainment at follow-up. For PPO, patients choose an outcome domain related to their goal from a pre-defined list at baseline, and complete a standardized questionnaire assessing the chosen outcome domain at baseline and follow-up. A feasibility study indicated that IOM had adequate completion (89%) and acceptability (96%) rates in a clinical sample (n = 84). IOM was then evaluated in a RCT (ISRCTN02507940). GA and PPO components were associated with each other and with the trial primary outcome. The use of the PPO component of IOM as the primary outcome could be considered in future RCTs. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

The Efficacy of Guanxinning Injection in Treating Angina Pectoris: Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Jia, Yongliang; Leung, Siu-wai; Lee, Ming-Yuen; Cui, Guozhen; Huang, Xiaohui; Pan, Fongha

2013-01-01

Objective. The randomized controlled trials (RCTs) on Guanxinning injection (GXN) in treating angina pectoris were published only in Chinese and have not been systematically reviewed. This study aims to provide a PRISMA-compliant and internationally accessible systematic review to evaluate the efficacy of GXN in treating angina pectoris. Methods. The RCTs were included according to prespecified eligibility criteria. Meta-analysis was performed to evaluate the symptomatic (SYMPTOMS) and electrocardiographic (ECG) improvements after treatment. Odds ratios (ORs) were used to measure effect sizes. Subgroup analysis, sensitivity analysis, and metaregression were conducted to evaluate the robustness of the results. Results. Sixty-five RCTs published between 2002 and 2012 with 6064 participants were included. Overall ORs comparing GXN with other drugs were 3.32 (95% CI: [2.72, 4.04]) in SYMPTOMS and 2.59 (95% CI: [2.14, 3.15]) in ECG. Subgroup analysis, sensitivity analysis, and metaregression found no statistically significant dependence of overall ORs upon specific study characteristics. Conclusion. This meta-analysis of eligible RCTs provides evidence that GXN is effective in treating angina pectoris. This evidence warrants further RCTs of higher quality, longer follow-up periods, larger sample sizes, and multicentres/multicountries for more extensive subgroup, sensitivity, and metaregression analyses. PMID:23634167

[Ultrafiltration versus intravenous diuretics in decompensated heart failure: a meta-analysis of randomized controlled trials].

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Zhao, Yu-liang; Zhang, Ling; Yang, Ying-ying; Tang, Yi; Liu, Fang; Fu, Ping

2013-08-13

To explore whether ultrafiltration is superior to intravenous diuretics in ameliorating fluid overload and preserving renal functions in decompensated heart failure patients. By searching in Pubmed, Cochrane Library, Embase, Springer, WanFang, CQVIP, CNKI and CBM database as well as related Chinese journals, qualified randomized controlled trials (RCTs) were included for meta-analysis by Revman 5.0 and STATA 10.0. Six RCTs were included with 241 patients in ultrafiltration group and 240 patients in intravenous diuretics group. Pooled analyses demonstrated ultrafiltration was superior to intravenous diuretics in the aspects of weight loss (WMD = 1.44 kg, 95%CI:0.33-2.55 kg, P = 0.01) and fluid removal (WMD = 1.23 kg, 95%CI:0.63-1.82 kg, P diuretics in mitigating fluid overload. No intergroup difference was observed in renal function preservation, mortality or rehospitalization.

A critical review of clinical trials in systemic lupus erythematosus

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Mahieu, Mary A.; Strand, Vibeke; Simon, Lee S.; Lipsky, Peter E.; Ramsey-Goldman, Rosalind

2016-01-01

One challenge in caring for patients with systemic lupus erythematosus (SLE) is a paucity of approved therapeutics for treatment of the diverse disease manifestations. In the last 60 years, only one drug, belimumab, has been approved for SLE treatment. Critical evaluation of investigator initiated and pharma-sponsored randomized controlled trials (RCTs) highlights barriers to successful drug development in SLE, including disease heterogeneity, inadequate trial size or duration, insufficient dose finding before initiation of large trials, handling of background medications, and choice of primary endpoint. Herein we examine lessons learned from landmark SLE RCTs and subsequent advances in trial design, as well as discuss efforts to address limitations in current SLE outcome measures that will improve detection of true therapeutic responses in future RCTs. PMID:27497257

Acupuncture and moxibustion for lateral elbow pain: a systematic review of randomized controlled trials

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2014-01-01

Background Acupuncture and moxibustion have widely been used to treat lateral elbow pain (LEP). A comprehensive systematic review of randomized controlled trials (RCTs) including both English and Chinese databases was conducted to assess the efficacy of acupuncture and moxibustion in the treatment of LEP. Methods Revised STRICTA (2010) criteria were used to appraise the acupuncture procedures, the Cochrane risk of bias tool was used to assess the methodological quality of the studies. A total of 19 RCTs that compared acupuncture and/or moxibustion with sham acupuncture, another form of acupuncture, or conventional treatment were included. Results All studies had at least one domain rated as high risk or uncertain risk of bias in the Cochrane risk of bias tool. Results from three RCTs of moderate quality showed that acupuncture was more effective than sham acupuncture. Results from 10 RCTs of mostly low quality showed that acupuncture or moxibustion was superior or equal to conventional treatment, such as local anesthetic injection, local steroid injection, non-steroidal anti- inflammatory drugs, or ultrasound. There were six low quality RCTs that compared acupuncture and moxibustion combined with manual acupuncture alone, and all showed that acupuncture and moxibustion combined was superior to manual acupuncture alone. Conclusion Moderate quality studies suggest that acupuncture is more effective than sham acupuncture. Interpretations of findings regarding acupuncture vs. conventional treatment, and acupuncture and moxibustion combined vs. manual acupuncture alone are limited by the methodological qualities of these studies. Future studies with improved methodological design are warranted to confirm the efficacy of acupuncture and moxibustion for LEP. PMID:24726029

Considerations for preparing a randomized population health intervention trial: lessons from a South African–Canadian partnership to improve the health of health workers

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Annalee Yassi

2014-05-01

Full Text Available Background: Community-based cluster-randomized controlled trials (RCTs are increasingly being conducted to address pressing global health concerns. Preparations for clinical trials are well-described, as are the steps for multi-component health service trials. However, guidance is lacking for addressing the ethical and logistic challenges in (cluster RCTs of population health interventions in low- and middle-income countries. Objective: We aimed to identify the factors that population health researchers must explicitly consider when planning RCTs within North–South partnerships. Design: We reviewed our experiences and identified key ethical and logistic issues encountered during the pre-trial phase of a recently implemented RCT. This trial aimed to improve tuberculosis (TB and Human Immunodeficiency Virus (HIV prevention and care for health workers by enhancing workplace assessment capability, addressing concerns about confidentiality and stigma, and providing onsite counseling, testing, and treatment. An iterative framework was used to synthesize this analysis with lessons taken from other studies. Results: The checklist of critical factors was grouped into eight categories: 1 Building trust and shared ownership; 2 Conducting feasibility studies throughout the process; 3 Building capacity; 4 Creating an appropriate information system; 5 Conducting pilot studies; 6 Securing stakeholder support, with a view to scale-up; 7 Continuously refining methodological rigor; and 8 Explicitly addressing all ethical issues both at the start and continuously as they arise. Conclusion: Researchers should allow for the significant investment of time and resources required for successful implementation of population health RCTs within North–South collaborations, recognize the iterative nature of the process, and be prepared to revise protocols as challenges emerge.

Chuna (or Tuina Manual Therapy for Musculoskeletal Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Nam-Woo Lee

2017-01-01

Full Text Available Objective. To review the literature and systematically evaluate the effectiveness of Chuna (or Tuina manual therapy (C[T]MT on pain and function for musculoskeletal disorders. Methods. We searched 15 English, Chinese, Japanese, and Korean databases using relevant keywords. All randomized controlled trials (RCTs of C(TMT for musculoskeletal disorders were considered, and we limited analyses to studies with a low-risk bias for randomization and/or allocation concealment. Results. Sixty-six RCTs with 6,170 participants were included. One sham-controlled RCT showed that C(TMT relieved pain more effectively than a sham control (SMD -3.09 [-3.59, -2.59]. For active-controlled RCTs, pooled meta-analysis showed that C(TMT had statistically significant effects on pain reduction, especially compared to traction (P<0.00001, drugs (P=0.04, and physical therapies (P<0.0001. For functional improvement, combined effects of C(TMT with drugs (P=0.04 and traction (P=0.05 also showed similar positive effects. Conclusions. This systematic review suggests that C(TMT is safe and effective for pain reduction and functional improvement for musculoskeletal diseases; however, the evidence for functional improvement was not as strong as for pain reduction. For future studies, high-quality RCTs such as sham-controlled studies with standardized interventions are needed to provide sufficient evidence on the effects of C(TMT for musculoskeletal diseases. Protocol registration number is CRD42016038307 04/07/2016.

Intermittent Cervical Traction for Treating Neck Pain: A Meta-analysis of Randomized Controlled Trials.

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Yang, Jheng-Dao; Tam, Ka-Wai; Huang, Tsai-Wei; Huang, Shih-Wei; Liou, Tsan-Hon; Chen, Hung-Chou

2017-07-01

A meta-analysis. The aim of this study was to perform a comprehensive search of current literature and conduct a meta-analysis of randomized controlled trials (RCTs) to assess the neck pain relieving effect of intermittent cervical traction (ICT). Neck pain is a common and disabling problem with a high prevalence in general population. It causes a considerable burden on the health care system with a substantial expenditure. ICT is a common component of physical therapy for neck pain in the outpatient clinic. However, the evidence regarding the effectiveness of ICT for neck pain is insufficient. Data were obtained from the PubMed, Cochrane Library, Embase, and Scopus databases from the database inception date to July 02, 2016. RCTs reporting the effects of ICT on neck pain, including those comparing the effects of ICT with those of a placebo treatment, were included. Two reviewers independently reviewed the studies, conducted a risk of bias assessment, and extracted data. The data were pooled in a meta-analysis by using a random-effects model. The meta-analysis included seven RCTs. The results indicated that patients who received ICT for neck pain had significantly lower pain scores than those receiving placebos did immediately after treatment (standardized mean difference = -0.26, 95% confidence interval = -0.46 to -0.07). The pain scores during the follow-up period and the neck disability index scores immediately after treatment and during the follow-up period did not differ significantly. ICT may have a short-term neck pain-relieving effect. Some risks of bias were noted in the included studies, reducing the evidence level of this meta-analysis. Additional high-quality RCTs are required to clarify the long-term effects of ICT on neck pain. 1.

Citations for Randomized Controlled Trials in Sepsis Literature: The Halo Effect Caused by Journal Impact Factor.

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Zhongheng Zhang

Full Text Available Citations for randomized controlled trials (RCT are important for the dissemination of study results. However, predictors of citations for RCTs have not been investigated. The study aimed to investigate the predictors of citations for RCTs in sepsis literature. RCTs that investigated the efficacy of treatment strategies on clinical outcomes in sepsis patients were included, and publication dates were restricted to the period from 2000 to 2016. Risk of bias was assessed using the Cochrane handbook for systematic reviews and interventions. A multivariable linear regression model was built to investigate the independent variables associated with total citations. In total, 160 RCTs met our inclusion criteria and were included for analysis. The median of total citations was 28.5 (IQR: 6-76. The journal impact factor (IF for articles was 6.312 (IQR: 3.143-7.214. The dependent variable was transformed by the square root to improve normality and meet the assumption of homoscedasticity. The journal IF (coefficient: 0.2; 95% CI: 0.16, 0.25 was independently associated with total citations. Large samples were associated with more total citations (coefficient: 0.0026; 95% CI: 0.0013, 0.0039. The study demonstrated that the journal IF was a major determinant of the RCT's total citation number.

Stroke rehabilitation evidence and comorbidity: a systematic scoping review of randomized controlled trials.

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Nelson, Michelle L A; McKellar, Kaileah A; Yi, Juliana; Kelloway, Linda; Munce, Sarah; Cott, Cheryl; Hall, Ruth; Fortin, Martin; Teasell, Robert; Lyons, Renee

2017-07-01

Most strokes occur in the context of other medical diagnoses. Currently, stroke rehabilitation evidence reviews have not synthesized or presented evidence with a focus on comorbidities and correspondingly may not align with current patient population. The purpose of this review was to determine the extent and nature of randomized controlled trial stroke rehabilitation evidence that included patients with multimorbidity. A systematic scoping review was conducted. Electronic databases were searched using a combination of terms related to "stroke" and "rehabilitation." Selection criteria captured inpatient rehabilitation studies. Methods were modified to account for the amount of literature, classified by study design, and randomized controlled trials (RCTs) were abstracted. The database search yielded 10771 unique articles. Screening resulted in 428 included RCTs. Three studies explicitly included patients with a comorbid condition. Fifteen percent of articles did not specify additional conditions that were excluded. Impaired cognition was the most commonly excluded condition. Approximately 37% of articles excluded patients who had experienced a previous stroke. Twenty-four percent excluded patients one or more Charlson Index condition, and 83% excluded patients with at least one other medical condition. This review represents a first attempt to map literature on stroke rehabilitation related to co/multimorbidity and identify gaps in existing research. Existing evidence on stroke rehabilitation often excluded individuals with comorbidities. This is problematic as the evidence that is used to generate clinical guidelines may not match the patient typically seen in practice. The use of alternate research methods are therefore needed for studying the care of individuals with stroke and multimorbidity.

Explaining feast or famine in randomized field trials. Medical science and criminology compared.

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Shepherd, Jonathan P

2003-06-01

A feast of randomized controlled trials (RCTs) in medical science and comparative famine in criminology can be explained in terms of cultural and structural factors. Of central importance is the context in which the evaluation of interventions is done and the difference in status of situational research in the two disciplines. Evaluation of medical interventions has traditionally been led by practitioner (clinical) academics. This is not the case in criminal justice, where theory has had higher status than intervention research. Medical science has advanced in, or closely associated with, university teaching hospitals, but links between criminology and criminal justice services are far more tenuous. The late development of situational crime prevention seems extraordinary from a medical perspective, as does the absence of university police schools in the United Kingdom and elsewhere. These structural and cultural factors explain concentration of expectation, resource, and RCT productivity in medical science. The Campbell Collaboration and the Academy of Experimental Criminology are forces which are reducing this polarization of feast and famine in RCTs. But unless scientific criminology is embedded in university schools which are responsible for the education and training of law, probation, and police practitioners, convergence in terms of RCTs and implementation of findings in practice seems unlikely.

How completely are physiotherapy interventions described in reports of randomised trials?

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Yamato, Tiê P; Maher, Chris G; Saragiotto, Bruno T; Hoffmann, Tammy C; Moseley, Anne M

2016-06-01

Incomplete descriptions of interventions are a common problem in reports of randomised controlled trials. To date no study has evaluated the completeness of the descriptions of physiotherapy interventions. To evaluate the completeness of the descriptions of physiotherapy interventions in a random sample of reports of randomised controlled trials (RCTs). A random sample of 200 reports of RCTs from the PEDro database. We included full text papers, written in English, and reporting trials with two arms. We included trials evaluating any type of physiotherapy interventions and subdisciplines. The methodological quality was evaluated using the PEDro scale and completeness of intervention description using the Template for Intervention Description and Replication (TIDieR) checklist. The proportion and 95% confidence interval were calculated for intervention and control groups, and used to present the relationship between completeness and methodological quality, and subdisciplines. Completeness of intervention reporting in physiotherapy RCTs was poor. For intervention groups, 46 (23%) trials did not describe at least half of the items. Reporting was worse for control groups, 149 (75%) trials described less than half of the items. There was no clear difference in the completeness across subdisciplines or methodological quality. Our sample were restricted to trials published in English in 2013. Descriptions of interventions in physiotherapy RCTs are typically incomplete. Authors and journals should aim for more complete descriptions of interventions in physiotherapy trials. Copyright © 2016 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

The use of the intention-to-treat principle in nursing clinical trials.

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Polit, Denise F; Gillespie, Brigid M

2009-01-01

In randomized controlled trials (RCTs), the intention-to-treat (ITT) principle, which involves maintaining study participants in the treatment groups to which they were randomized regardless of postrandomization withdrawal, is the recommended analytic approach for preserving the integrity of randomization, yet little is known about the use of ITT in nursing RCTs. The purpose of this study was to describe the extent to which nurse researchers who conduct RCTs state that they have used ITT, the extent to which they adhere to ITT principles, and the methods they use to handle missing data. Data regarding ITT analysis, participant flow, rates of attrition, and methods of handling missing data were extracted and coded from a consecutive sample of 124 RCTs published in 16 nursing journals in 2007 and 2008. ITT was declared in only 15.3% of the nursing RCTs, and a definition of ITT was offered in fewer than half of these studies. On the basis of the authors' descriptions of analytic procedures, it was concluded that 10.5% of those claiming ITT use had used a per-protocol analysis rather than an ITT analysis. Overall, 46.8% of the RCTs were classified as having either a classic or a modified ITT analysis, indicating that many nurse researchers are not stating their actual adherence to ITT, despite advice to do so in the Consolidated Standards of Reporting Trials guidelines. Nurse researchers conducting RCTs should be more diligent in following the Consolidated Standards of Reporting Trials guidelines about ITT, documenting ITT use in their reports, clarifying their definition of ITT, and presenting flowcharts that describe subject flow. Readers of nursing reports, in evaluating evidence from RCTs, should not rely on stated use of ITT but should examine how analyses were conducted.

Reporting methods of blinding in randomized trials assessing nonpharmacological treatments.

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Isabelle Boutron

2007-02-01

Full Text Available BACKGROUND: Blinding is a cornerstone of treatment evaluation. Blinding is more difficult to obtain in trials assessing nonpharmacological treatment and frequently relies on "creative" (nonstandard methods. The purpose of this study was to systematically describe the strategies used to obtain blinding in a sample of randomized controlled trials of nonpharmacological treatment. METHODS AND FINDINGS: We systematically searched in Medline and the Cochrane Methodology Register for randomized controlled trials (RCTs assessing nonpharmacological treatment with blinding, published during 2004 in high-impact-factor journals. Data were extracted using a standardized extraction form. We identified 145 articles, with the method of blinding described in 123 of the reports. Methods of blinding of participants and/or health care providers and/or other caregivers concerned mainly use of sham procedures such as simulation of surgical procedures, similar attention-control interventions, or a placebo with a different mode of administration for rehabilitation or psychotherapy. Trials assessing devices reported various placebo interventions such as use of sham prosthesis, identical apparatus (e.g., identical but inactivated machine or use of activated machine with a barrier to block the treatment, or simulation of using a device. Blinding participants to the study hypothesis was also an important method of blinding. The methods reported for blinding outcome assessors relied mainly on centralized assessment of paraclinical examinations, clinical examinations (i.e., use of video, audiotape, photography, or adjudications of clinical events. CONCLUSIONS: This study classifies blinding methods and provides a detailed description of methods that could overcome some barriers of blinding in clinical trials assessing nonpharmacological treatment, and provides information for readers assessing the quality of results of such trials.

Placement Of Cardiac PacemaKEr Trial (POCKET – rationale and design: a randomized controlled trial

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Peter Magnusson

2017-04-01

Full Text Available BackgroundA pacemaker system consists of one or two leads connected to a device that is implanted into a pocket formed just below the collarbone. This pocket is typically subcutaneous, that is, located just above the pectoral fascia. Even though the size of pacemakers has decreased markedly, complications due to superficial implants do occur. An alternative technique would be intramuscular placement of the pacemaker device, but there are no randomized controlled trials (RCTs to support this approach, which is the rationale for the Placement Of Cardiac PacemaKEr Trial (POCKET. The aim is to study if intramuscular is superior to subcutaneous placement of a pacemaker pocket.MethodsIn October 2016, we started to enroll 200 consecutive patients with an indication for bradycardia pacemaker implantation. Patients are randomized to random block sizes, stratified by age group (cut-off: 65 years and sex, and then randomized to either subcutaneous or intramuscular implant. A concealed allocation procedure is employed, using sequentially numbered, sealed envelopes. Pocket site is blinded to the patient and in all subsequent care. The primary endpoint is patient overall satisfaction with the pocket location at 24 months as measured using a visual analog scale (VAS 0-10. Secondary endpoints are: complications, patient-reported satisfaction at 1, 12, and 24 months (overall satisfaction, pain, discomfort, degree of unsightly appearance, movement problems, and sleep problems due to device.ConclusionsPOCKET is a prospective interventional RCT designed to evaluate if intramuscular is superior to subcutaneous placement of a bradycardia pacemaker during a two-year follow-up.

Placement Of Cardiac PacemaKEr Trial (POCKET – rationale and design: a randomized controlled trial

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Peter Magnusson

2017-04-01

Full Text Available Background: A pacemaker system consists of one or two leads connected to a device that is implanted into a pocket formed just below the collarbone. This pocket is typically subcutaneous, that is, located just above the pectoral fascia. Even though the size of pacemakers has decreased markedly, complications due to superficial implants do occur. An alternative technique would be intramuscular placement of the pacemaker device, but there are no randomized controlled trials (RCTs to support this approach, which is the rationale for the Placement Of Cardiac PacemaKEr Trial (POCKET. The aim is to study if intramuscular is superior to subcutaneous placement of a pacemaker pocket. Methods: In October 2016, we started to enroll 200 consecutive patients with an indication for bradycardia pacemaker implantation. Patients are randomized to random block sizes, stratified by age group (cut-off: 65 years and sex, and then randomized to either subcutaneous or intramuscular implant. A concealed allocation procedure is employed, using sequentially numbered, sealed envelopes. Pocket site is blinded to the patient and in all subsequent care. The primary endpoint is patient overall satisfaction with the pocket location at 24 months as measured using a visual analog scale (VAS 0-10. Secondary endpoints are: complications, patient-reported satisfaction at 1, 12, and 24 months (overall satisfaction, pain, discomfort, degree of unsightly appearance, movement problems, and sleep problems due to device. Conclusions: POCKET is a prospective interventional RCT designed to evaluate if intramuscular is superior to subcutaneous placement of a bradycardia pacemaker during a two-year follow-up.

Acupuncture for Functional Dyspepsia: What Strength Does It Have? A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Li, Jing; Li, Bo; Hu, Ya-Cai; Cai, Qiu-Han

2016-01-01

Background. Although the effectiveness of acupuncture therapy on functional dyspepsia (FD) has been systematically reviewed, the available reports are still contradictive and no robust evidence has been provided to date. Objective. To assess the current evidence of high quality on the effects of acupuncture for patients with FD. Methods. A comprehensive literature database search was conducted to identify randomized controlled trials (RCTs) comparing acupuncture therapies (including manual acupuncture and electroacupuncture) to sham acupuncture and medication use. A meta-analysis was performed following a strict methodology. Results. 16 RCTs involving 1436 participants were included. The majority of the trials were determined to be of low quality. Positive results were found for acupuncture in improving the Nepean Dyspepsia Index (NDI) and scores of the MOS 36-Item Short-Form Health Survey (SF-36), as well as in alleviating relevant symptoms (especially postprandial fullness and early satiation) of FD patients. Conclusion. Based on current available evidence, acupuncture therapy achieves statistically significant effect for FD in comparison with sham acupuncture and is superior to medication (prokinetic agents) in improving the symptoms and quality of life of FD patients. Nonetheless, despite stringent methodological analyses, the conclusion of our review still needs to be strengthened by additional RCTs of higher quality. PMID:28119758

A Systematic Review and Meta-Analysis Estimating the Expected Dropout Rates in Randomized Controlled Trials on Yoga Interventions.

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Cramer, Holger; Haller, Heidemarie; Dobos, Gustav; Lauche, Romy

2016-01-01

A reasonable estimation of expected dropout rates is vital for adequate sample size calculations in randomized controlled trials (RCTs). Underestimating expected dropouts rates increases the risk of false negative results while overestimating rates results in overly large sample sizes, raising both ethical and economic issues. To estimate expected dropout rates in RCTs on yoga interventions, MEDLINE/PubMed, Scopus, IndMED, and the Cochrane Library were searched through February 2014; a total of 168 RCTs were meta-analyzed. Overall dropout rate was 11.42% (95% confidence interval [CI] = 10.11%, 12.73%) in the yoga groups; rates were comparable in usual care and psychological control groups and were slightly higher in exercise control groups (rate = 14.53%; 95% CI = 11.56%, 17.50%; odds ratio = 0.82; 95% CI = 0.68, 0.98; p = 0.03). For RCTs with durations above 12 weeks, dropout rates in yoga groups increased to 15.23% (95% CI = 11.79%, 18.68%). The upper border of 95% CIs for dropout rates commonly was below 20% regardless of study origin, health condition, gender, age groups, and intervention characteristics; however, it exceeded 40% for studies on HIV patients or heterogeneous age groups. In conclusion, dropout rates can be expected to be less than 15 to 20% for most RCTs on yoga interventions. Yet dropout rates beyond 40% are possible depending on the participants' sociodemographic and health condition.

Systematic Review of Infrapopliteal Drug-Eluting Stents: A Meta-Analysis of Randomized Controlled Trials

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Katsanos, Konstantinos, E-mail: katsanos@med.upatras.gr [NHS Foundation Trust, King' s Health Partners, Department of Interventional Radiology, Guy' s and St. Thomas' Hospitals (United Kingdom); Spiliopoulos, Stavros [Patras University Hospital, Department of Interventional Radiology, School of Medicine (Greece); Diamantopoulos, Athanasios [NHS Foundation Trust, King' s Health Partners, Department of Interventional Radiology, Guy' s and St. Thomas' Hospitals (United Kingdom); Karnabatidis, Dimitris [Patras University Hospital, Department of Interventional Radiology, School of Medicine (Greece); Sabharwal, Tarun [NHS Foundation Trust, King' s Health Partners, Department of Interventional Radiology, Guy' s and St. Thomas' Hospitals (United Kingdom); Siablis, Dimitris [Patras University Hospital, Department of Interventional Radiology, School of Medicine (Greece)

2013-06-15

IntroductionDrug-eluting stents (DES) have been proposed for the treatment of infrapopliteal arterial disease. We performed a systematic review to provide a qualitative analysis and quantitative data synthesis of randomized controlled trials (RCTs) assessing infrapopliteal DES.Materials and MethodsPubMed (Medline), EMBASE (Excerpta Medical Database), AMED (Allied and Complementary medicine Database), Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), online content, and abstract meetings were searched in September 2012 for eligible RCTs according to the preferred reporting items for systematic reviews and meta-analyses selection process. Risk of bias was assessed using the Cochrane Collaboration's tool. Primary endpoint was primary patency defined as absence of {>=}50 % vessel restenosis at 1 year. Secondary outcome measures included patient survival, limb amputations, change of Rutherford-Becker class, target lesion revascularization (TLR) events, complete wound healing, and event-free survival at 1 year. Risk ratio (RRs) were calculated using the Mantel-Haenszel fixed effects model, and number-needed-to-treat values are reported.ResultsThree RCTs involving 501 patients with focal infrapopliteal lesions were analyzed (YUKON-BTX, DESTINY, and ACHILLES trials). All three RCTs included relatively short and focal infrapopliteal lesions. At 1 year, there was clear superiority of infrapopliteal DES compared with control treatments in terms of significantly higher primary patency (80.0 vs. 58.5 %; pooled RR = 1.37, 95 % confidence interval [CI] = 1.18-1.58, p < 0.0001; number-needed-to-treat (NNT) value = 4.8), improvement of Rutherford-Becker class (79.0 vs. 69.6 %; pooled RR = 1.13, 95 % CI = 1.002-1.275, p = 0.045; NNT = 11.1), decreased TLR events (9.9 vs. 22.0 %; pooled RR = 0.45, 95 % CI = 0.28-0.73, p = 0.001; NNT = 8.3), improved wound healing (76.8 vs. 59.7 %; pooled RR = 1.29, 95 % CI = 1.02-1.62, p = 0.04; NNT = 5.9), and better overall

Systematic Review of Infrapopliteal Drug-Eluting Stents: A Meta-Analysis of Randomized Controlled Trials

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Katsanos, Konstantinos; Spiliopoulos, Stavros; Diamantopoulos, Athanasios; Karnabatidis, Dimitris; Sabharwal, Tarun; Siablis, Dimitris

2013-01-01

IntroductionDrug-eluting stents (DES) have been proposed for the treatment of infrapopliteal arterial disease. We performed a systematic review to provide a qualitative analysis and quantitative data synthesis of randomized controlled trials (RCTs) assessing infrapopliteal DES.Materials and MethodsPubMed (Medline), EMBASE (Excerpta Medical Database), AMED (Allied and Complementary medicine Database), Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), online content, and abstract meetings were searched in September 2012 for eligible RCTs according to the preferred reporting items for systematic reviews and meta-analyses selection process. Risk of bias was assessed using the Cochrane Collaboration’s tool. Primary endpoint was primary patency defined as absence of ≥50 % vessel restenosis at 1 year. Secondary outcome measures included patient survival, limb amputations, change of Rutherford–Becker class, target lesion revascularization (TLR) events, complete wound healing, and event-free survival at 1 year. Risk ratio (RRs) were calculated using the Mantel–Haenszel fixed effects model, and number-needed-to-treat values are reported.ResultsThree RCTs involving 501 patients with focal infrapopliteal lesions were analyzed (YUKON-BTX, DESTINY, and ACHILLES trials). All three RCTs included relatively short and focal infrapopliteal lesions. At 1 year, there was clear superiority of infrapopliteal DES compared with control treatments in terms of significantly higher primary patency (80.0 vs. 58.5 %; pooled RR = 1.37, 95 % confidence interval [CI] = 1.18–1.58, p < 0.0001; number-needed-to-treat (NNT) value = 4.8), improvement of Rutherford–Becker class (79.0 vs. 69.6 %; pooled RR = 1.13, 95 % CI = 1.002–1.275, p = 0.045; NNT = 11.1), decreased TLR events (9.9 vs. 22.0 %; pooled RR = 0.45, 95 % CI = 0.28–0.73, p = 0.001; NNT = 8.3), improved wound healing (76.8 vs. 59.7 %; pooled RR = 1.29, 95 % CI = 1.02–1.62, p = 0.04; NNT = 5.9), and better

Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials.

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Guoyan Yang

Full Text Available Huperzine A is a Chinese herb extract used for Alzheimer's disease. We conducted this review to evaluate the beneficial and harmful effect of Huperzine A for treatment of Alzheimer's disease.We searched for randomized clinical trials (RCTs of Huperzine A for Alzheimer's disease in PubMed, Cochrane Library, and four major Chinese electronic databases from their inception to June 2013. We performed meta-analyses using RevMan 5.1 software. (Protocol ID: CRD42012003249.20 RCTs including 1823 participants were included. The methodological quality of most included trials had a high risk of bias. Compared with placebo, Huperzine A showed a significant beneficial effect on the improvement of cognitive function as measured by Mini-Mental State Examination (MMSE at 8 weeks, 12 weeks and 16 weeks, and by Hastgawa Dementia Scale (HDS and Wechsler Memory Scale (WMS at 8 weeks and 12 weeks. Activities of daily living favored Huperzine A as measured by Activities of Daily Living Scale (ADL at 6 weeks, 12 weeks and 16 weeks. One trial found Huperzine A improved global clinical assessment as measured by Clinical Dementia Rating Scale (CDR. One trial demonstrated no significant change in cognitive function as measured by Alzheimer's disease Assessment Scale-Cognitive Subscale (ADAS-Cog and activity of daily living as measured by Alzheimer's disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL in Huperzine A group. Trials comparing Huperzine A with no treatment, psychotherapy and conventional medicine demonstrated similar findings. No trial evaluated quality of life. No trial reported severe adverse events of Huperzine A.Huperzine A appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment in participants with Alzheimer's disease. However, the findings should be interpreted with caution due to the poor methodological quality of the included trials.

Efficacy and safety of oxcarbazepine in the treatment of children with epilepsy: a meta-analysis of randomized controlled trials.

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Geng, Hua; Wang, Chengzhong

2017-01-01

To assess the efficacy and safety of oxcarbazepine (OXC) in the treatment of children with epilepsy. Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, Cochrane Library, Scopus, SinoMed (Chinese BioMedical Literature Service System, China), and Chinese National Knowledge Infrastructure (China) database were systematically reviewed. Eligible studies were those that compared the efficacy and safety of OXC with other antiepileptic drugs in epilepsy. Risk ratio (RR) with 95% confidence intervals (95% CIs) was calculated using fixed-effects or random-effects model. Eleven RCTs with a total of 1,241 patients met the inclusion criteria and were included in this meta-analysis. Compared with other antiepileptic drugs (sodium valproate, levetiracetam, phenytoin, and placebo), OXC was associated with similar seizure-free rate (RR =1.06, 95% CI: 0.94, 1.20; P =0.366) and percentage reduction from baseline in seizure frequency (for ≥75% reduction: RR =1.15, 95% CI: 0.88, 1.49; P =0.310; for 50%-75% reduction: RR =1.12, 95% CI: 0.90, 1.39; P =0.301; for effects and safety as other antiepileptic drugs in the treatment of children with epilepsy. Further well-conducted, large-scale RCTs are needed to validate these findings.

Stereotactic aspiration versus craniotomy for primary intracerebral hemorrhage: a meta-analysis of randomized controlled trials.

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Jia-Wei Wang

Full Text Available BACKGROUND: A wealth of evidence based on the randomized controlled trials (RCTs has indicated that surgery may be a better choice in the management of primary intracerebral hemorrhage (ICH compared to conservative treatment. However, there is considerable controversy over selecting appropriate surgical procedures for ICH. Thus, this meta-analysis was performed to assess the effects of stereotactic aspiration compared to craniotomy in patients with ICH. METHODS: According to the study strategy, we searched PUBMED, EMBASE and Cochrane Central Register of Controlled Trials. Other sources such as the internet-based clinical trial registries, relevant journals and the lists of references were also searched. After literature searching, two investigators independently performed literature screening, assessment of quality of the included trials and data extraction. The outcome measures included death or dependence, total risk of complication, and the risk of rebleeding, gastrointestinal hemorrhage and systematic infection. RESULTS: Four RCTs with 2996 participants were included. The quality of the included trials was acceptable. Stereotactic aspiration significantly decreased the odds of death or dependence at the final follow-up (odds ratio (OR: 0.80, 95% confidence interval (CI: 0.69-0.93; P = 0.004 and the risk of intracerebral rebleeding (OR: 0.44, 95% CI: 0.26-0.74; P = 0.002 compared to craniotomy with no significant heterogeneity among the study results. CONCLUSIONS: The present meta-analysis provides evidence that the stereotactic aspiration may be associated with a reduction in the odds of being dead or dependent in primary ICH, which should be interpreted with caution. Further trials are needed to identify those patients most likely to benefit from the stereotactic aspiration.

Long-Term Efficacy of Maintenance Therapy for Multiple Myeloma: A Quantitative Synthesis of 22 Randomized Controlled Trials

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Jie-Li Li

2018-04-01

Full Text Available We aimed to quantitatively synthesize data from randomized controlled trials (RCTs concerning maintenance for multiple myeloma (MM. We searched electronic literature databases and conference proceedings to identify relevant RCTs. We selected eligible RCTs using predefined selection criteria. We conducted meta-analysis comparing maintenance containing new agents and conventional maintenance, and subgroup analysis by transplantation status and mainstay agent as well. We performed trial sequential analysis (TSA to determine adequacy of sample size for overall and subgroup meta-analyses. We performed network meta-analysis (NMA to compare and rank included regimens. A total of 22 RCTs involving 9,968 MM patients and 15 regimens were included, the overall quality of which was adequate. Significant heterogeneity was detected for progression-free survival (PFS but not overall survival (OS. Meta-analyses showed that maintenance containing new agents significantly improved PFS but not OS [PFS: Hazard Ratio (HR = 0.59, 95% Confidence Interval (CI = 0.54 to 0.64; OS: HR = 0.93, 95% CI = 0.87 to 1.00], compared with controls. Subgroup analyses revealed lenalidomide (Len-based therapies better than thalidomide-based ones (HR = 0.50 and 0.66, respectively; P = 0.001. NMA revealed that most of the maintenance regimens containing new agents were significantly better than simple observation in terms of PFS but not OS. Len single agent was the most effective, considering PFS and OS both. We concluded that conventional maintenance has very limited effect. Maintenance containing new agents is highly effective in improving PFS, but has very limited effect on OS. Maintenance with Len may have the largest survival benefits. Emerging strategies may further change the landscape of maintenance of MM.

Clinical trial registration in oral health journals.

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Smaïl-Faugeron, V; Fron-Chabouis, H; Durieux, P

2015-03-01

Prospective registration of randomized controlled trials (RCTs) represents the best solution to reporting bias. The extent to which oral health journals have endorsed and complied with RCT registration is unknown. We identified journals publishing RCTs in dentistry, oral surgery, and medicine in the Journal Citation Reports. We classified journals into 3 groups: journals requiring or recommending trial registration, journals referring indirectly to registration, and journals providing no reference to registration. For the 5 journals with the highest 2012 impact factors in each group, we assessed whether RCTs with results published in 2013 had been registered. Of 78 journals examined, 32 (41%) required or recommended trial registration, 19 (24%) referred indirectly to registration, and 27 (35%) provided no reference to registration. We identified 317 RCTs with results published in the 15 selected journals in 2013. Overall, 73 (23%) were registered in a trial registry. Among those, 91% were registered retrospectively and 32% did not report trial registration in the published article. The proportion of trials registered was not significantly associated with editorial policies: 29% with results in journals that required or recommended registration, 15% in those that referred indirectly to registration, and 21% in those providing no reference to registration (P = 0.05). Less than one-quarter of RCTs with results published in a sample of oral health journals were registered with a public registry. Improvements are needed with respect to how journals inform and require their authors to register their trials. © International & American Associations for Dental Research.

Iron deficiency anemia in Helicobacter pylori infection: meta-analysis of randomized controlled trials.

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Yuan, Wenzhen; Li Yumin; Yang Kehu; Ma Bin; Guan Quanlin; Wang, Donghai; Yang, Lijuan

2010-06-01

Helicobacter pylori (H. pylori) infection and iron deficiency anemia are prevalent in disadvantaged populations worldwide. The benefit of H. pylori eradiation for iron deficiency anemia has been extensively studied, but data are still equivocal. A search in The Cochrane Library, PUBMED, EMBASE, EBM Review databases, Science Citation Index Expanded, and CMB (Chinese Biomedical Literature Database) was performed. Randomized controlled trials (RCTs) comparing anti-H. pylori plus oral iron to oral iron alone for the iron deficiency patients in whom H. pylori was positive were selected for meta-analysis. Reviev Manager 5.0 software was used for the performance of meta-analysis. Sixteen randomized controlled trials totaling 956 patients were included. The meta-analysis showed that the difference from baseline to endpoint of hemoglobin (Hb), serum iron (SI), and serum ferritin (SF) was statistically significantly different between anti-H. pylori treatment plus oral iron and oral iron alone (SMD, Hb 1.48; 95% CI, 0.96, 2.00; p infection could be effective in improving anemia and iron statue in IDA patients infected by H. pylori, particularly in patients with moderate or severe anemia.

Chinese Medicine Injection Qingkailing for Treatment of Acute Ischemia Stroke: A Systematic Review of Randomized Controlled Trials

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Fafeng Cheng

2012-01-01

Full Text Available Qingkailing (QKL injection was a famous traditional Chinese patent medicine, which was extensively used to treat the acute stages of cerebrovascular disease. The aim of this study was to assess the quantity, quality and overall strength of the evidence on QKL in the treatment of acute ischemic stroke. Methods. An extensive search was performed within MEDLINE, Cochrane, CNKI, Vip and Wan-Fang up to November 2011. Randomized controlled trails (RCTs on QKL for treatment of acute stroke were collected, irrespective of languages. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards, and RevMan5 was used for data analysis. Results. 7 RCTs (545 patients were included and the methodological quality was evaluated as generally low. The pooled results showed that QKL combined with conventional treatment was more effective in effect rate, and the score of MESSS and TNF-α level compared with conventional treatment alone, but there was no significant difference in mortality of two groups. Only one trial reported routine life status. There were four trials reported adverse events, and no obvious adverse event occurred in three trials while one reported adverse events described as eruption and dizziness.

Lessons learned in a clinical trial for military sexual trauma-related posttraumatic stress disorder

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Alina Surís, PhD; Nicholas Holder, BS; Ryan Holliday, MA; E. Ellen Morris, PhD

2016-01-01

A large body of literature exists describing the challenges associated with implementing randomized controlled clinical trials (RCTs) [1]. However, when clinical trials are conducted within Department of Veterans Affairs (VA) Medical Center (VAMC) settings, several additional and unique factors contribute to the difficulty of conducting RCTs. The challenges and strategies to address them, described in this editorial, are based on an RCT conducted to determi...

Does the use of consumer health information technology improve outcomes in the patient self-management of diabetes? A meta-analysis and narrative review of randomized controlled trials.

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Or, Calvin K L; Tao, Da

2014-05-01

To assess whether the use of consumer health information technologies (CHITs) improves outcomes in the patient self-management of diabetes. The evidence from randomized controlled trials (RCTs) on the effects of CHITs on patient outcomes was analyzed using either meta-analysis or a narrative synthesis approach. A systematic search of seven electronic databases was conducted to identify relevant reports of RCTs for the analysis. In the meta-analyses, standardized mean differences in patient outcomes were calculated and random-effects models were applied in cases where the heterogeneity of the results was moderate or high, otherwise fixed-effects models were used. Sixty-two studies, representing 67 RCTs, met the inclusion criteria. The results of the meta-analyses showed that the use of CHITs was associated with significant reductions in HbA1c, blood pressure, total cholesterol, and triglycerides levels when compared with the usual care. The findings from the narrative synthesis indicated that only a small proportion of the trials reported positive effects of CHITs on patient outcomes. The use of CHITs in supporting diabetes self-management appears to have potential benefits for patients' self-management of diabetes. However, the effectiveness of the technologies in improving patient outcomes still awaits confirmation in future studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials.

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Giuseppe Grosso

Full Text Available BACKGROUND: Despite omega-3 polyunsaturated fatty acids (PUFA supplementation in depressed patients have been suggested to improve depressive symptomatology, previous findings are not univocal. OBJECTIVES: To conduct an updated meta-analysis of randomized controlled trials (RCTs of omega-3 PUFA treatment of depressive disorders, taking into account the clinical differences among patients included in the studies. METHODS: A search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of RCTs using omega-3 PUFA on patients with depressive symptoms published up to August 2013 was performed. Standardized mean difference in clinical measure of depression severity was primary outcome. Type of omega-3 used (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] and omega-3 as mono- or adjuvant therapy was also examined. Meta-regression analyses assessed the effects of study size, baseline depression severity, trial duration, dose of omega-3, and age of patients. RESULTS: Meta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD and patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized difference in random-effects model 0.56 SD [95% CI: 0.20, 0.92] and 0.22 SD [95% CI: 0.01, 0.43], respectively; pooled analysis was 0.38 SD [95% CI: 0.18, 0.59]. Use of mainly EPA within the preparation, rather than DHA, influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations

Role of Omega-3 Fatty Acids in the Treatment of Depressive Disorders: A Comprehensive Meta-Analysis of Randomized Clinical Trials

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Grosso, Giuseppe; Pajak, Andrzej; Marventano, Stefano; Castellano, Sabrina; Galvano, Fabio; Bucolo, Claudio; Drago, Filippo; Caraci, Filippo

2014-01-01

Background Despite omega-3 polyunsaturated fatty acids (PUFA) supplementation in depressed patients have been suggested to improve depressive symptomatology, previous findings are not univocal. Objectives To conduct an updated meta-analysis of randomized controlled trials (RCTs) of omega-3 PUFA treatment of depressive disorders, taking into account the clinical differences among patients included in the studies. Methods A search on MEDLINE, EMBASE, PsycInfo, and the Cochrane Database of RCTs using omega-3 PUFA on patients with depressive symptoms published up to August 2013 was performed. Standardized mean difference in clinical measure of depression severity was primary outcome. Type of omega-3 used (particularly eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and omega-3 as mono- or adjuvant therapy was also examined. Meta-regression analyses assessed the effects of study size, baseline depression severity, trial duration, dose of omega-3, and age of patients. Results Meta-analysis of 11 and 8 trials conducted respectively on patients with a DSM-defined diagnosis of major depressive disorder (MDD) and patients with depressive symptomatology but no diagnosis of MDD demonstrated significant clinical benefit of omega-3 PUFA treatment compared to placebo (standardized difference in random-effects model 0.56 SD [95% CI: 0.20, 0.92] and 0.22 SD [95% CI: 0.01, 0.43], respectively; pooled analysis was 0.38 SD [95% CI: 0.18, 0.59]). Use of mainly EPA within the preparation, rather than DHA, influenced final clinical efficacy. Significant clinical efficacy had the use of omega-3 PUFA as adjuvant rather than mono-therapy. No relation between efficacy and study size, baseline depression severity, trial duration, age of patients, and study quality was found. Omega-3 PUFA resulted effective in RCTs on patients with bipolar disorder, whereas no evidence was found for those exploring their efficacy on depressive symptoms in young populations, perinatal depression

Imbalance p values for baseline covariates in randomized controlled trials: a last resort for the use of p values? A pro and contra debate.

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Stang, Andreas; Baethge, Christopher

2018-01-01

Results of randomized controlled trials (RCTs) are usually accompanied by a table that compares covariates between the study groups at baseline. Sometimes, the investigators report p values for imbalanced covariates. The aim of this debate is to illustrate the pro and contra of the use of these p values in RCTs. Low p values can be a sign of biased or fraudulent randomization and can be used as a warning sign. They can be considered as a screening tool with low positive-predictive value. Low p values should prompt us to ask for the reasons and for potential consequences, especially in combination with hints of methodological problems. A fair randomization produces the expectation that the distribution of p values follows a flat distribution. It does not produce an expectation related to a single p value. The distribution of p values in RCTs can be influenced by the correlation among covariates, differential misclassification or differential mismeasurement of baseline covariates. Given only a small number of reported p values in the reports of RCTs, judging whether the realized p value distribution is, indeed, a flat distribution becomes difficult. If p values ≤0.005 or ≥0.995 were used as a sign of alarm, the false-positive rate would be 5.0% if randomization was done correctly, and five p values per RCT were reported. Use of a low p value as a warning sign that randomization is potentially biased can be considered a vague heuristic. The authors of this debate are obviously more or less enthusiastic with this heuristic and differ in the consequences they propose.

The relationship between external and internal validity of randomized controlled trials: A sample of hypertension trials from China.

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Zhang, Xin; Wu, Yuxia; Ren, Pengwei; Liu, Xueting; Kang, Deying

2015-10-30

To explore the relationship between the external validity and the internal validity of hypertension RCTs conducted in China. Comprehensive literature searches were performed in Medline, Embase, Cochrane Central Register of Controlled Trials (CCTR), CBMdisc (Chinese biomedical literature database), CNKI (China National Knowledge Infrastructure/China Academic Journals Full-text Database) and VIP (Chinese scientific journals database) as well as advanced search strategies were used to locate hypertension RCTs. The risk of bias in RCTs was assessed by a modified scale, Jadad scale respectively, and then studies with 3 or more grading scores were included for the purpose of evaluating of external validity. A data extract form including 4 domains and 25 items was used to explore relationship of the external validity and the internal validity. Statistic analyses were performed by using SPSS software, version 21.0 (SPSS, Chicago, IL). 226 hypertension RCTs were included for final analysis. RCTs conducted in university affiliated hospitals (P internal validity. Multi-center studies (median = 4.0, IQR = 2.0) were scored higher internal validity score than single-center studies (median = 3.0, IQR = 1.0) (P internal validity (P = 0.004). Multivariate regression indicated sample size, industry-funding, quality of life (QOL) taken as measure and the university affiliated hospital as trial setting had statistical significance (P external validity of RCTs do associate with the internal validity, that do not stand in an easy relationship to each other. Regarding the poor reporting, other possible links between two variables need to trace in the future methodological researches.

Acupoint Stimulation for Fibromyalgia: A Systematic Review of Randomized Controlled Trials

Directory of Open Access Journals (Sweden)

Huijuan Cao

2013-01-01

Full Text Available Background. Acupoint stimulation is popular for treatment of fibromyalgia though there is lack of comprehensive evaluation of current clinical evidence for its effect and safety. Objective. To systematically review the beneficial effects and safety of acupoint stimulation for fibromyalgia. Methods. We searched six electronic databases for randomized trials on acupoint stimulation for treatment of fibromyalgia. Two authors extracted data and assessed the trial quality independently. RevMan 5.2 software was used for data analyses with effect estimate presented as (standard mean difference and a 95% confidence interval. We defined minimum, medium, and large SMD effect sizes as 0.3, 0.5, and 0.75. Results. 16 RCTs with 1081 participants were involved in this review. Only two trials were evaluated as low risk of bias. Meta-analysis showed that acupuncture alone or combined with cupping therapy was superior to conventional medications on reducing pain scores and/or the number of tender points. However, acupuncture showed no better than sham acupuncture on pain reduction. There was no serious adverse event reported to be related to acupoint stimulation. Conclusions. Acupoint stimulation appears to be effective in treating fibromyalgia compared with medications. However, further large, rigorously designed trials are warranted due to insufficient methodological rigor in the included trials.

Patent foramen ovale closure versus medical therapy after cryptogenic stroke: An updated meta-analysis of all randomized clinical trials.

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Kheiri, Babikir; Abdalla, Ahmed; Osman, Mohammed; Ahmed, Sahar; Hassan, Mustafa; Bachuwa, Ghassan

2018-03-07

Cryptogenic strokes can be attributed to paradoxical emboli through patent foramen ovale (PFO). However, the effectiveness of PFO closure in preventing recurrent stroke is uncertain and the results of previous randomized clinical trials (RCTs) have been inconclusive. Hence, this study provides an updated meta-analysis of all RCTs comparing PFO closure with medical therapy for secondary prevention of cryptogenic stroke. All RCTs were identified by a comprehensive literature search of PubMed, Embase, the Cochrane Collaboration Central Register of Controlled Trials, Scopus, and Clinicaltrials.gov. The primary outcome was recurrent ischemic stroke and secondary outcomes were transient ischemic attack (TIA), all-cause mortality, new-onset atrial fibrillation (AF), serious adverse events, and major bleeding. 5 RCTs with 3440 participants were included in the present study (1829 patients underwent PFO closure and 1611 were treated medically). Pooled analysis showed a statistically significant reduction in the rate of recurrent stroke with PFO closure in comparison to medical therapy (OR 0.41; 95% CI 0.19-0.90; p = 0.03). However, there were no statistically significant reductions of recurrent TIAs (OR 0.77; 95% CI 0.51-1.14; p = 0.19) or all-cause mortality (OR 0.76; 95% CI 0.35-1.65; p = 0.48). The risk of developing new-onset AF was increased significantly with PFO closure (OR 4.74; 95% CI 2.33-9.61; p Patent foramen ovale closure in adults with recent cryptogenic stroke was associated with a lower rate of recurrent strokes in comparison with medical therapy alone.

Update on clinical trials in Dysphagia.

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Logemann, Jeri A

2006-04-01

Randomized clinical trials (RCTs) are often known as the gold standard in treatment efficacy studies. This article defines the characteristics of RCTs and the factors that investigators must consider in designing clinical trials in dysphagia. Design issues unique to behavioral treatments often used in dysphagia are discussed. Ongoing RCTs in dysphagia are described including studies of (1) the effectiveness of the Shaker exercise versus standardized treatment in patients with severe dysphagia resulting from stroke or treatment for head and neck cancer who have been nonoral for at least three months; (2) the comparative effects of nectar- and honey-thickened liquids versus chin tuck posture and in patients with dementia or Parkinson's disease with or without dementia who aspirate on thin liquids; and (3) the comparative effects of muscle exercise versus sensory postural therapy for dysphagia resulting from treatment for head and neck cancer. Issues in generalizing from the results of clinical trials are also described.

Cognitive-behavioral therapy for body dysmorphic disorder: A systematic review and meta-analysis of randomized controlled trials.

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Harrison, Amy; Fernández de la Cruz, Lorena; Enander, Jesper; Radua, Joaquim; Mataix-Cols, David

2016-08-01

Body dysmorphic disorder (BDD) is a chronic and disabling psychiatric disorder unlikely to remit without treatment. A systematic review and meta-analysis of randomized controlled trials (RCTs) of cognitive-behavioral therapy (CBT) for BDD was conducted, including published and unpublished trials to 26th November 2015. Primary outcomes were validated BDD measures; secondary outcomes included depression and insight. Meta-regressions were conducted to examine potential effects of variables on the primary outcome, including socio-demographic variables, comorbidity, symptom severity/duration, concomitant medication, treatment duration, and methodological quality of the RCTs. Seven RCTs (N=299) met inclusion criteria. CBT was superior to waitlist or credible psychological placebo in reducing BDD (7 studies; delta=-1.22, 95% CI=-1.66 to -0.79) and depression symptoms (5 studies; delta=-0.49, 95% CI=-0.76 to -0.22). CBT was associated with improvements in insight/delusionality (4 studies; delta=-0.56, 95% CI=-0.93 to -0.19). Improvement in BDD was maintained after 2-4months follow-up (3 studies; delta=-0.89, 95% CI=-1.24 to -0.54). Meta-regression analyses did not reveal any significant predictors of outcome. CBT is an efficacious treatment for BDD but there is substantial room for improvement. The specificity and long-term effects of CBT for BDD require further evaluation using credible control conditions. Additional trials comparing CBT with pharmacological therapies, as well as their combination, are warranted. Tele-care options, such as Internet-based CBT, hold great promise to increase access to evidence-based treatment for a majority of patients who need it and should be evaluated further. Copyright © 2016 Elsevier Ltd. All rights reserved.

Searches for Randomized Controlled Trials of Drugs in MEDLINE and EMBASE Using Only Generic Drug Names Compared with Searches Applied in Current Practice in Systematic Reviews

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Waffenschmidt, Siw; Guddat, Charlotte

2015-01-01

Background: It is unclear which terms should be included in bibliographic searches for randomized controlled trials (RCTs) of drugs, and identifying relevant drug terms can be extremely laborious. The aim of our analysis was to determine whether a bibliographic search using only the generic drug name produces sufficient results for the generation…

Milligan-Morgan (Open) Versus Ferguson Haemorrhoidectomy (Closed): A Systematic Review and Meta-Analysis of Published Randomized, Controlled Trials.

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Bhatti, Muhammad I; Sajid, Muhammad Shafique; Baig, Mirza K

2016-06-01

The purpose of this article is to systematically analyse the randomized, controlled trials (RCTs) comparing Ferguson or closed haemorrhoidectomy (CH) versus open haemorrhoidectomy (OH) or Milligan-Morgan haemorrhoidectomy in the management of haemorrhoidal disease (HD). RCTs on the effectiveness of CH and OH in the management of HD were analysed systematically using RevMan(®), and combined outcome was expressed as odds ratio (OR) and standardized mean difference. Eleven CRTs encompassing 1326 patients were analysed systematically. There was significant heterogeneity among included trials. Therefore, in the random effects model, CH was associated with a reduced post-operative pain (SMD, -0.36; 95 % CI, -0.64, -0.07; z = 2.45; p = 0.01), faster wound healing (OR, 0.08; 95 % CI, 0.02, 0.24; z = 4.33; p SMD, 6.10; 95 % CI, 3.21, 8.98; z = 4.13; p SMD, -0.33; 95 % CI, -0.68, 0.03; z = 1.82; p = 0.07), length of hospital stay, post-operative complications, HD recurrence and risk of surgical site infection were similar in both groups. CH has clinically measurable advantages over OH in terms of reduced post-operative pain, lower risk of post-operative bleeding and faster wound healing.

Atherectomy of the femoropopliteal artery: a systematic review and meta-analysis of randomized controlled trials.

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Diamantopoulos, A; Katsanos, K

2014-10-01

A systematic review was performed to provide a qualitative analysis and quantitative data synthesis of randomized controlled trials (RCTs) assessing debulking atherectomy versus balloon angioplasty for treatment of femoropopliteal artery occlusive disease. PubMed (MEDLINE), EMBASE, AMED, Scopus, online content and meeting abstracts were searched in May 2014 for eligible RCTs following the PRISMA selection process. Risk of bias was assessed using the Cochrane Collaboration's tool. Pooled risks were calculated with a random effects model to account for clinical and conceptual heterogeneity. Sensitivity analysis was employed to test the robustness of the results. Six RCTs comprising 287 patients (328 lesions) treated with either debulking atherectomy or balloon angioplasty for femoropopliteal artery disease were analyzed and synthesized. Technical success was similar between the atherectomy and the angioplasty group (93.6% vs. 96.2%, RR: 0.99. 95%CI: 0.95-1.03, P=0.57, I(2)=0%). Need for bail-out stenting and distal arterial embolization were largely similar between atherectomy and balloon angioplasty alone. After a median follow-up of 9 months the 2 groups showed similar primary patency (RR: 0.90, 95%CI: 0.56-1.46, P=0.68, I(2)=69%). Only 2 low-quality studies reported amputation and mortality rates, both of which were found significantly less in the atherectomy arms. Analysis of a limited body of low quality evidence with high risk of bias showed that debulking atherectomy of the femoropopliteal artery does not seem to confer any procedural advantage or improvement of clinical outcomes over balloon angioplasty alone.

Omitted Data in Randomized Controlled Trials for Anxiety and Depression: A Systematic Review of the Inclusion of Sexual Orientation and Gender Identity

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Heck, Nicholas C.; Mirabito, Lucas A.; LeMaire, Kelly; Livingston, Nicholas A.; Flentje, Annesa

2016-01-01

Objective The current study examined the frequency with which randomized controlled trials (RCTs) of behavioral and psychological interventions for anxiety and depression include data pertaining to participant sexual orientation and non-binary gender identities. Method Using systematic review methodology, the databases PubMed and PsycINFO were searched to identify RCTs published in 2004, 2009, and 2014. Random selections of 400 articles per database per year (2400 articles in total) were considered for inclusion in the review. Articles meeting inclusion criteria were read and coded by the research team to identify whether the trial reported data pertaining to participant sexual orientation and non-binary gender identities. Additional trial characteristics were also identified and indexed in our database (e.g., sample size, funding source etc.). Results Of the 232 articles meeting inclusion criteria, only one reported participants’ sexual orientation and zero articles included non-binary gender identities. A total of 52,769 participants were represented in the trials, 93 of which were conducted in the U.S. and 43 acknowledged the National Institutes of Health as a source of funding. Conclusions Despite known mental health disparities on the basis of sexual orientation and non-binary gender identification, researchers evaluating interventions for anxiety and depression are not reporting on these important demographic characteristics. Reporting practices must change in order to ensure that our interventions generalize to lesbian, gay, bisexual, and transgender persons. PMID:27845517

Off-label use of recombinant factor VIIa for treatment of haemorrhage: results from randomized clinical trials

DEFF Research Database (Denmark)

Johansson, Per Ingemar

2008-01-01

) for evidence of such an approach. Methods In October 2007, a review of RCT involving rFVIIa for non-haemophilic indications was performed. The effect of rFVIIa on blood loss and transfusion requirements was recorded. Results Seventeen RCTs were identified concerning different bleeding conditions, for example......, secondary to surgery, infection and stem cell transplantation. Three pilot studies reported a significant reduction in transfusion requirements and/or blood loss in the rFVIIa-treated groups, but these have not been confirmed in large randomized trials. No difference in thromboembolic complications between...

The optimization of treatment and management of schizophrenia in Europe (OPTiMiSE) trial

DEFF Research Database (Denmark)

Leucht, Stefan; Winter-van Rossum, Inge; Heres, Stephan

2015-01-01

Commission sponsored "Optimization of Treatment and Management of Schizophrenia in Europe" (OPTiMiSE) trial which aims to provide a treatment algorithm for patients with a first episode of schizophrenia. METHODS: We searched Pubmed (October 29, 2014) for randomized controlled trials (RCTs) that examined...... switching the drug in nonresponders to another antipsychotic. We described important methodological choices of the OPTiMiSE trial. RESULTS: We found 10 RCTs on switching antipsychotic drugs. No trial was conclusive and none was concerned with first-episode schizophrenia. In OPTiMiSE, 500 first episode...

Comparative effects of meditation and exercise on physical and psychosocial health outcomes: a review of randomized controlled trials.

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Edwards, Meghan K; Loprinzi, Paul D

2018-03-01

No review papers have examined studies that have directly compared non-active forms of meditation with exercise to evaluate effects on physical or psychosocial outcomes, which was the purpose of this paper. Studies were included if they had a randomized controlled trial (RCT) design, included a non-active form of meditation and exercise as intervention arms, and evaluated physical or psychosocial outcomes. The quality of included RCTs was rated using the Cochrane Collaboration's tool for assessing risk of bias in randomized trials. Five RCTs met the inclusion criteria. The total sample size across all studies was N = 325. Of the main outcomes assessed across the five studies, meditation was shown to be more effective than the exercise comparison arm when evaluating the psychosocial outcomes of anxiety, altruism, and life changes. Additionally, meditation was more effective at reducing chronic neck pain at rest and pain-related bothersomeness. Exercise, however, was more effective in improving physical health-related quality of life, HDL and LDL cholesterol, and fasting blood glucose levels. The interventions were found to be comparable when evaluating the outcomes of well-being, ethanol consumption, and perceived stress levels. Four of the evaluated studies were determined to have an overall 'unclear' risk of bias and one study was found to have a 'high' risk of bias. Exercise and non-active meditation may uniquely influence various health-related outcomes. A continued exploration of the effects of exercise and non-active meditation in controlled trials may yield a better understanding of their benefits.

Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Sehatzadeh, Shayan; Tu, Hong Anh; Palimaka, Stefan; Yap, Belinda; O'Reilly, Daria; Bowen, Jim; Higgins, Caroline; Holubowich, Corinne

2016-01-01

Background To date, several randomized controlled trials (RCTs) have shown the efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depression. Objective This analysis examined the antidepressant efficacy of rTMS in patients with treatment-resistant unipolar depression. Methods A literature search was performed for RCTs published from January 1, 1994, to November 20, 2014. The search was updated on March 1, 2015. Two independent reviewers evaluated the abstracts for inclusion, reviewed full texts of eligible studies, and abstracted data. Meta-analyses were conducted to obtain summary estimates. The primary outcome was changes in depression scores measured by the Hamilton Rating Scale for Depression (HRSD), and we considered, a priori, the mean difference of 3.5 points to be a clinically important treatment effect. Remission and response to the treatment were secondary outcomes, and we calculated number needed to treat on the basis of these outcomes. We examined the possibility of publication bias by constructing funnel plots and by Begg's and Egger's tests. A meta-regression was undertaken to examine the effect of specific rTMS technical parameters on the treatment effects. Results Twenty-three RCTs compared rTMS with sham, and six RCTs compared rTMS with electroconvulsive therapy (ECT). Trials of rTMS versus sham showed a statistically significant improvement in depression scores with rTMS (weighted mean difference [WMD] 2.31, 95% CI 1.19–3.43; P transcranial magnetic stimulation had a small short-term effect for improving depression in comparison with sham, but follow-up studies did not show that the small effect will continue for longer periods. PMID:27099642

Strategies for prevention of postoperative delirium: a systematic review and meta-analysis of randomized trials

Science.gov (United States)

2013-01-01

Introduction The ideal measures to prevent postoperative delirium remain unestablished. We conducted this systematic review and meta-analysis to clarify the significance of potential interventions. Methods The PRISMA statement guidelines were followed. Two researchers searched MEDLINE, EMBASE, CINAHL and the Cochrane Library for articles published in English before August 2012. Additional sources included reference lists from reviews and related articles from 'Google Scholar'. Randomized clinical trials (RCTs) on interventions seeking to prevent postoperative delirium in adult patients were included. Data extraction and methodological quality assessment were performed using predefined data fields and scoring system. Meta-analysis was accomplished for studies that used similar strategies. The primary outcome measure was the incidence of postoperative delirium. We further tested whether interventions effective in preventing postoperative delirium shortened the length of hospital stay. Results We identified 38 RCTs with interventions ranging from perioperative managements to pharmacological, psychological or multicomponent interventions. Meta-analysis showed dexmedetomidine sedation was associated with less delirium compared to sedation produced by other drugs (two RCTs with 415 patients, pooled risk ratio (RR) = 0.39; 95% confidence interval (CI) = 0.16 to 0.95). Both typical (three RCTs with 965 patients, RR = 0.71; 95% CI = 0.54 to 0.93) and atypical antipsychotics (three RCTs with 627 patients, RR = 0.36; 95% CI = 0.26 to 0.50) decreased delirium occurrence when compared to placebos. Multicomponent interventions (two RCTs with 325 patients, RR = 0.71; 95% CI = 0.58 to 0.86) were effective in preventing delirium. No difference in the incidences of delirium was found between: neuraxial and general anesthesia (four RCTs with 511 patients, RR = 0.99; 95% CI = 0.65 to 1.50); epidural and intravenous analgesia (three RCTs with 167 patients, RR = 0.93; 95% CI = 0.61 to 1

[Dengzhan Xixin injection as an adjuvant treatment for angina pectoris: a systematic review and Meta-analysis of randomized controlled trials].

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Wang, Feng-jiao; Xie, Yan-ming; Liao, Xing; Jia, Min

2015-08-01

The paper is to systematically evaluate the efficacy and safety of Deng Zhan Xi Xin injection ( DZXXI) as an adjuvant treatment for patients with angina pectoris. The Cochrane Library, Medline, EMbase, CBM, CNKI, VIP, and Wan fang Data base were searched. Randomized controlled trials (RCTs) of DZXXI combined with western medicine routine treatment versus western medicine routine treatment alone for angina pectoris patients were all included. All trials were assessed according to the Cochrane Reviewer' s Handbook 5.1 for Systematic Reviews of Intervention and Meta analyses were performed by RevMan 5. 2 Software. A total of 30RCTs (3 086 patients including 1 572 patients of treatment group and 1 514 patients of control group) were included. Meta-analysis of treatment group compared with control group showed superior effect over reducing cardiovascular events ( OR = 0.33; 95% CI: [0.16, 0.67], P = 0.002, improving effective rate of DZXXI as adjuvant treatment for angina pectoris patients (OR = 3.97; 95% CI: [3.15, 5.02]; P angina pectoris. But based on the limitations of the study, rigorous design with long follow up clinical trials are necessary for further evidence.

Huangqi Jianzhong Tang for Treatment of Chronic Gastritis: A Systematic Review of Randomized Clinical Trials

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Wei, Yue; Ma, Li-Xin; Yin, Sheng-Jun; An, Jing; Wei, Qi; Yang, Jin-Xiang

2015-01-01

To assess the clinical effects and safety of Huangqi Jianzhong Tang (HQJZ) for the treatment of chronic gastritis (CG), three English databases and four Chinese databases were searched through the inception to January 2015. In randomized controlled trials (RCTs) comparing HQJZ with placebo, no intervention and western medicine were included. A total of 9 RCTs involving 979 participants were identified. The methodological quality of the included trials was generally poor. Meta-analyses demonstrated that HQJZ plus conventional medicine was more effective in improving overall gastroscopy outcome than western medicine alone for treatment of chronic superficial gastritis with the pooling result of overall improvement [OR 3.78 (1.29,11.06), P = 0.02]. In addition, the combination of HQJZ with antibiotics has higher overall effect rate than antibiotics alone for the treatment of CG [OR 2.60 (1.49,4.54), P = 0.0007]. There were no serious adverse events reported in both the intervention and controlled groups. HQJZ has the potential of improvement of the patients' gastroscopy outcomes, Helicobacter pylori clearance rate, traditional Chinese Medicine syndromes, and overall effect rate alone or in combination use with conventional western medicine for chronic atrophic gastritis. However, due to poor methodological quality, the beneficial effect and safeties of HQJZ for CG could not be confirmed. PMID:26819622

Potential link between excess added sugar intake and ectopic fat: a systematic review of randomized controlled trials.

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Ma, Jiantao; Karlsen, Micaela C; Chung, Mei; Jacques, Paul F; Saltzman, Edward; Smith, Caren E; Fox, Caroline S; McKeown, Nicola M

2016-01-01

The effect of added sugar intake on ectopic fat accumulation is a subject of debate. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to examine the potential effect of added sugar intake on ectopic fat depots. MEDLINE, CAB Abstracts, CAB Global Health, and EBM (Evidence-Based Medicine) Reviews - Cochrane Central Register of Controlled Trials databases were searched for studies published from 1973 to September 2014. RCTs with a minimum of 6 days' duration of added sugar exposure in the intervention group were selected. The dosage of added sugar intake as a percentage of total energy was extracted or calculated. Means and standard deviations of pre- and post-test measurements or changes in ectopic fat depots were collected. Fourteen RCTs were included. Most of the studies had a medium to high risk of bias. Meta-analysis showed that, compared with eucaloric controls, subjects who consumed added sugar under hypercaloric conditions likely increased ectopic fat, particularly in the liver (pooled standardized mean difference = 0.9 [95%CI, 0.6-1.2], n = 6) and muscles (pooled SMD = 0.6 [95%CI, 0.2-1.0], n = 4). No significant difference was observed in liver fat, visceral adipose tissue, or muscle fat when isocaloric intakes of different sources of added sugars were compared. Data from a limited number of RCTs suggest that excess added sugar intake under hypercaloric diet conditions likely increases ectopic fat depots, particularly in the liver and in muscle fat. There are insufficient data to compare the effect of different sources of added sugars on ectopic fat deposition or to compare intake of added sugar with intakes of other macronutrients. Future well-designed RCTs with sufficient power and duration are needed to address the role of sugars on ectopic fat deposition. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For

OARSI Clinical Trials Recommendations

DEFF Research Database (Denmark)

Emery, C. A.; Roos, Ewa M.; Verhagen, E.

2015-01-01

The risk of post-traumatic osteoarthritis (PTOA) substantially increases following joint injury. Research efforts should focus on investigating the efficacy of preventative strategies in high quality randomized controlled trials (RCT). The objective of these OARSI RCT recommendations is to inform...... the design, conduct and analytical approaches to RCTs evaluating the preventative effect of joint injury prevention strategies. Recommendations regarding the design, conduct, and reporting of RCTs evaluating injury prevention interventions were established based on the consensus of nine researchers...... internationally with expertise in epidemiology, injury prevention and/or osteoarthritis (OA). Input and resultant consensus was established through teleconference, face to face and email correspondence over a 1 year period. Recommendations for injury prevention RCTs include context specific considerations...

Training health professionals to recruit into challenging randomized controlled trials improved confidence: the development of the QuinteT randomized controlled trial recruitment training intervention.

Science.gov (United States)

Mills, Nicola; Gaunt, Daisy; Blazeby, Jane M; Elliott, Daisy; Husbands, Samantha; Holding, Peter; Rooshenas, Leila; Jepson, Marcus; Young, Bridget; Bower, Peter; Tudur Smith, Catrin; Gamble, Carrol; Donovan, Jenny L

2018-03-01

The objective of this study was to describe and evaluate a training intervention for recruiting patients to randomized controlled trials (RCTs), particularly for those anticipated to be difficult for recruitment. One of three training workshops was offered to surgeons and one to research nurses. Self-confidence in recruitment was measured through questionnaires before and up to 3 months after training; perceived impact of training on practice was assessed after. Data were analyzed using two-sample t-tests and supplemented with findings from the content analysis of free-text comments. Sixty-seven surgeons and 32 nurses attended. Self-confidence scores for all 10 questions increased after training [range of mean scores before 5.1-6.9 and after 6.9-8.2 (scale 0-10, all 95% confidence intervals are above 0 and all P-values recruitment following training was high-surgeons' mean score 8.8 [standard deviation (SD), 1.2] and nurses' 8.4 (SD, 1.3) (scale 0-10); 50% (19/38) of surgeons and 40% (10/25) of nurses reported on a 4-point Likert scale that training had made "a lot" of difference to their RCT discussions. Analysis of free text revealed this was mostly in relation to how to convey equipoise, explain randomization, and manage treatment preferences. Surgeons and research nurses reported increased self-confidence in discussing RCTs with patients, a raised awareness of hidden challenges and a positive impact on recruitment practice following QuinteT RCT Recruitment Training. Training will be made more available and evaluated in relation to recruitment rates and informed consent. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A Systematic Review and Meta-Analysis Estimating the Expected Dropout Rates in Randomized Controlled Trials on Yoga Interventions

Directory of Open Access Journals (Sweden)

Holger Cramer

2016-01-01

Full Text Available A reasonable estimation of expected dropout rates is vital for adequate sample size calculations in randomized controlled trials (RCTs. Underestimating expected dropouts rates increases the risk of false negative results while overestimating rates results in overly large sample sizes, raising both ethical and economic issues. To estimate expected dropout rates in RCTs on yoga interventions, MEDLINE/PubMed, Scopus, IndMED, and the Cochrane Library were searched through February 2014; a total of 168 RCTs were meta-analyzed. Overall dropout rate was 11.42% (95% confidence interval [CI] = 10.11%, 12.73% in the yoga groups; rates were comparable in usual care and psychological control groups and were slightly higher in exercise control groups (rate = 14.53%; 95% CI = 11.56%, 17.50%; odds ratio = 0.82; 95% CI = 0.68, 0.98; p=0.03. For RCTs with durations above 12 weeks, dropout rates in yoga groups increased to 15.23% (95% CI = 11.79%, 18.68%. The upper border of 95% CIs for dropout rates commonly was below 20% regardless of study origin, health condition, gender, age groups, and intervention characteristics; however, it exceeded 40% for studies on HIV patients or heterogeneous age groups. In conclusion, dropout rates can be expected to be less than 15 to 20% for most RCTs on yoga interventions. Yet dropout rates beyond 40% are possible depending on the participants’ sociodemographic and health condition.

Effects of Fentanyl on Emergence Agitation in Children under Sevoflurane Anesthesia: Meta-Analysis of Randomized Controlled Trials

Science.gov (United States)

Xiong, Wei; Zhou, Qin; Yang, Peng; Huang, Xiongqing

2015-01-01

Background and Objectives The goal of this meta-analysis study was to assess the effects of fentanyl on emergence agitation (EA) under sevoflurane anesthesia in children. Subjects and Methods We searched electronic databases (PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials) for articles published until December 2014. Randomized controlled trials (RCTs) that assessed the effects of fentanyl and placebo on EA under sevoflurane anesthesia in children that the outcome were the incidence of EA, postoperative pain, emergence time or adverse effects were included in this meta-analysis. Results A total of 16 studies, including 1362 patients (737 patients for the fentanyl group and 625 for the placebo group), were evaluated in final analysis. We found that administration of fentanyl decreased the incidences of EA (RR = 0.37, 95% CI 0.27~0.49, Pfentanyl decreases the incidence of EA under sevoflurane anesthesia in children and postoperative pain, but has a higher incidence of PONV. Considering the inherent limitations of the included studies, more RCTs with extensive follow-up should be performed to validate our findings in the future. PMID:26275039

Non-inferiority trials: methodological and regulatory challenges

NARCIS (Netherlands)

Wangge, G.

2012-01-01

A randomized clinical trial (RCT) is the gold standard to evaluate the intended effects of drugs. In such trials a drug can be compared with a placebo or with another active compound for the same indication. RCTs can be used to demonstrate that a drug is superior to placebo or an active comparator

Combined versus single application of tranexamic acid in total knee and hip arthroplasty: A meta-analysis of randomized controlled trials.

Science.gov (United States)

Peng Zhang, M M; Jifeng Li, M M; Xiao Wang, M M

2017-07-01

To compare the efficacy and safety of the combined application of both intravenous and topical tranexamic acid versus the single use of either application in patients with total knee and hip arthroplasty. Potentially relevant studies were identified from electronic databases including Medline, PubMed, Embase, ScienceDirect and the Cochrane Library. Patients undergoing primary total knee and hip arthroplasty were included in our studies, with an experimental group that received combined intravenous and topical application of tranexamic acid and a control group that received a single application of tranexamic acid or normal saline. The primary outcomes were total blood loss, hemoglobin decline and transfusion requirements. The secondary outcomes were length of stay, operation time and tranexamic acid-related adverse effects, such as superficial infection, deep vein thrombosis or pulmonary embolism. Modified Jadad scores were used to assess the quality of the included randomized controlled trials (RCTs). The data was pooled using RevMan 5.3. After testing for heterogeneity across studies, the data were aggregated using random-effects modeling when appropriate. We have registered the trial at http://www.researchregistry.com. Six RCTs that included 704 patients met the inclusion criteria. The present meta-analysis indicated significant differences existed in the total blood loss (MD = -134.65, 95% CI: -191.66 to -77.64, P tranexamic acid in total knee and hip arthroplasty was associated with significantly reduced total blood loss, postoperative hemoglobin decline, drainage volume, and transfusion requirements. Based on the limitations of current meta-analysis, well-designed, high-quality RCTs with long-term follow-up are still required. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Comparison of intra-articular hyaluronic acid and methylprednisolone for pain management in knee osteoarthritis: A meta-analysis of randomized controlled trials.

Science.gov (United States)

Ran, Jian; Yang, Xiaohui; Ren, Zheng; Wang, Jian; Dong, Hui

2018-05-01

We performed a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of intra-articular methylprednisolone and hyaluronic acid (HA) in term of pain reduction and improvements of knee function in patients with knee osteoarthritis (OA). The PubMed, EMBASE, ScienceDirect, and Cochrane Library databases were systematically searched for literature up to January 2018. RCTs involving HA and methylprednisolone in knee OA were included. Two independent reviewers performed independent data abstraction. The I 2 statistic was used to assess heterogeneity. A fixed or random effects model was adopted for meta-analysis. All meta-analyses were performed by using STATA 14.0. Five RCTs with 1004 patients were included in the meta-analysis. The present meta-analysis indicated that there were no significant differences in terms of WOMAC pain, physical function and stiffness at 4 week, 12 weeks and 26 weeks between HA and methylprednisolone groups. No increased risk of adverse events were identified in both groups. Both HA and methylprednisolone injections were effective therapies for patients with knee OA. Methylprednisolone showed comparable efficacy in reducing pain and improving functional recovery to HA. And no significant difference was found in long-term of follow-up in terms of adverse effects. Copyright © 2018 IJS Publishing Group Ltd. All rights reserved.

Financial ties of principal investigators and randomized controlled trial outcomes: cross sectional study.

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Ahn, Rosa; Woodbridge, Alexandra; Abraham, Ann; Saba, Susan; Korenstein, Deborah; Madden, Erin; Boscardin, W John; Keyhani, Salomeh

2017-01-17

 To examine the association between the presence of individual principal investigators' financial ties to the manufacturer of the study drug and the trial's outcomes after accounting for source of research funding.  Cross sectional study of randomized controlled trials (RCTs).  Studies published in "core clinical" journals, as identified by Medline, between 1 January 2013 and 31 December 2013.  Random sample of RCTs focused on drug efficacy.  Association between financial ties of principal investigators and study outcome.  A total of 190 papers describing 195 studies met inclusion criteria. Financial ties between principal investigators and the pharmaceutical industry were present in 132 (67.7%) studies. Of 397 principal investigators, 231 (58%) had financial ties and 166 (42%) did not. Of all principal investigators, 156 (39%) reported advisor/consultancy payments, 81 (20%) reported speakers' fees, 81 (20%) reported unspecified financial ties, 52 (13%) reported honorariums, 52 (13%) reported employee relationships, 52 (13%) reported travel fees, 41 (10%) reported stock ownership, and 20 (5%) reported having a patent related to the study drug. The prevalence of financial ties of principal investigators was 76% (103/136) among positive studies and 49% (29/59) among negative studies. In unadjusted analyses, the presence of a financial tie was associated with a positive study outcome (odds ratio 3.23, 95% confidence interval 1.7 to 6.1). In the primary multivariate analysis, a financial tie was significantly associated with positive RCT outcome after adjustment for the study funding source (odds ratio 3.57 (1.7 to 7.7). The secondary analysis controlled for additional RCT characteristics such as study phase, sample size, country of first authors, specialty, trial registration, study design, type of analysis, comparator, and outcome measure. These characteristics did not appreciably affect the relation between financial ties and study outcomes (odds ratio 3.37, 1

Vitamin D and new-onset atrial fibrillation: A meta-analysis of randomized controlled trials.

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Huang, Wei-Ling; Yang, Jun; Yang, Jian; Wang, Hui-Bo; Yang, Chao-Jun; Yang, Ying

2017-11-14

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, which affects 1.5% to 2% of the general population. More than six million Europeans suffer from AF. To research vitamin D levels in the prevention of new-onset atrial fibrillation (AF), we conducted a systematic review of randomized controlled trials (RCTs). We focused on the vitamin D levels in the prevention of new-onset AF. The outcomes assessed were vitamin D levels, left ventricular ejection fraction (LVEF), and left atrium diameter. Six RCTs ultimately met the inclusion criteria in the meta-analysis. The outcomes of Vitamin D levels (MD = -4.27, 95% CI = -5.20 to-3.34, P = 0.30) in the new-onset AF showed no significant difference. The left atrium diameter (MD = 1.96, 95% CI = 1.48 to 2.60, P new-onset AF and LVEF (MD = -0.92, 95% CI = -1.59 to -0.26, P new-onset AF. Copyright © 2017 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Informing hot flash treatment decisions for breast cancer survivors: a systematic review of randomized trials comparing active interventions.

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Johns, Claire; Seav, Susan M; Dominick, Sally A; Gorman, Jessica R; Li, Hongying; Natarajan, Loki; Mao, Jun James; Irene Su, H

2016-04-01

Patient-centered decision making about hot flash treatments often incorporates a balance of efficacy and side effects in addition to patient preference. This systematic review examines randomized controlled trials (RCTs) comparing at least two non-hormonal hot flash treatments in breast cancer survivors. In July 2015, PubMed, SCOPUS, CINAHL, Cochrane, and Web of Science databases were searched for RCTs comparing active, non-hormonal hot flash treatments in female breast cancer survivors. Thirteen trials were included after identifying 906 potential studies. Four trials were dose comparison studies of pharmacologic treatments citalopram, venlafaxine, gabapentin, and paroxetine. Hot flash reduction did not differ by tamoxifen or aromatase inhibitor use. Citalopram 10, 20, and 30 mg daily had comparable outcomes. Venlafaxine 75 mg daily improved hot flashes without additional side effects from higher dosing. Gabapentin 900 mg daily improved hot flashes more than 300 mg. Paroxetine 10 mg daily had fewer side effects than 20 mg. Among four trials comparing different pharmacologic treatments, venlafaxine alleviated hot flash symptoms faster than clonidine; participants preferred venlafaxine over gabapentin. Five trials compared pharmacologic to non-pharmacologic treatments. Acupuncture had similar efficacy to venlafaxine and gabapentin but may have longer durability after completing treatment and fewer side effects. We could not perform a pooled meta-analysis because outcomes were not reported in comparable formats. Clinical trial data on non-hormonal hot flash treatments provide comparisons of hot flash efficacy and other patient important outcomes to guide clinical management. Clinicians can use the information to help patients select hot flash interventions.

Aerobic exercise effects upon cognition in Mild Cognitive Impairment: A systematic review of randomized controlled trials.

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Cammisuli, D M; Innocenti, A; Franzoni, F; Pruneti, C

2017-07-01

Several studies have shown that physical activity has positive effects on cognition in healthy older adults without cognitive complains but lesser is known about the effectiveness of aerobic exercise in patients suffering from Mild Cognitive Impairment (MCI). The aim of the present study was to systematically review the evidence from randomized controlled trials (RCTs) about the effects of aerobic exercise upon cognition in MCI patients. To this end, PubMed, Cochrane and Web of Science databases were analytically searched for RCTs including aerobic exercise interventions for MCI patients. There is evidence that aerobic exercise improves cognition in MCI patients. Overall research reported moderate effects for global cognition, logical memory, inhibitory control and divided attention. Due to methodological limitations of the investigated studies, findings should be interpreted with caution. Standardized training protocols, larger scale interventions and follow-ups may also provide better insight into the preventive effects of aerobic exercise on cognitive deterioration in MCI and its conversion into dementia.

A substantial and confusing variation exists in handling of baseline covariates in randomized controlled trials: a review of trials published in leading medical journals.

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Austin, Peter C; Manca, Andrea; Zwarenstein, Merrick; Juurlink, David N; Stanbrook, Matthew B

2010-02-01

Statisticians have criticized the use of significance testing to compare the distribution of baseline covariates between treatment groups in randomized controlled trials (RCTs). Furthermore, some have advocated for the use of regression adjustment to estimate the effect of treatment after adjusting for potential imbalances in prognostically important baseline covariates between treatment groups. We examined 114 RCTs published in the New England Journal of Medicine, the Journal of the American Medical Association, The Lancet, and the British Medical Journal between January 1, 2007 and June 30, 2007. Significance testing was used to compare baseline characteristics between treatment arms in 38% of the studies. The practice was very rare in British journals and more common in the U.S. journals. In 29% of the studies, the primary outcome was continuous, whereas in 65% of the studies, the primary outcome was either dichotomous or time-to-event in nature. Adjustment for baseline covariates was reported when estimating the treatment effect in 34% of the studies. Our findings suggest the need for greater editorial consistency across journals in the reporting of RCTs. Furthermore, there is a need for greater debate about the relative merits of unadjusted vs. adjusted estimates of treatment effect. Copyright 2010 Elsevier Inc. All rights reserved.

The effects of probiotics on total cholesterol: A meta-analysis of randomized controlled trials.

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Wang, Lang; Guo, Mao-Juan; Gao, Qing; Yang, Jin-Feng; Yang, Lin; Pang, Xiao-Li; Jiang, Xi-Juan

2018-02-01

Probiotics supplements provide a new nonpharmacological alternative to reduce cardiovascular risk factors. The impact of probiotics on the reduction of total cholesterol (TC) remains controversial. We conducted a meta-analysis to showcase the most updated and comprehensive evaluation of the studies. Randomized controlled trials (RCTs) were searched from electronic databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang database dating from January 2007 to January 2017. The curative effects of probiotics on the reduction of TC were assessed using mean difference (MD), as well as their 95% confidence interval (CI). RevMan software (version 5.3) was used to carry out this meta-analysis. Thirty-two RCTs including 1971 patients met the inclusion criteria. Results of this analysis showed that compared with the control group serum TC was significantly reduced in probiotics group [MD = -13.27, 95% CI (-16.74 to 9.80), P  6 weeks: [MD = -22.18, 95% CI (-28.73, -15.63), P probiotics forms and intervention duration might have a significant impact on the results. However, strains and doses of probiotics had no significant influence on curative effects. Available evidence indicates that probiotics supplements can significantly reduce serum TC. Furthermore, higher baseline TC, longer intervention time, and probiotics in capsules form might contribute to a better curative effect.

Developing evidence-based dentistry skills: how to interpret randomized clinical trials and systematic reviews.

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Kiriakou, Juliana; Pandis, Nikolaos; Madianos, Phoebus; Polychronopoulou, Argy

2014-10-30

Decision-making based on reliable evidence is more likely to lead to effective and efficient treatments. Evidence-based dentistry was developed, similarly to evidence-based medicine, to help clinicians apply current and valid research findings into their own clinical practice. Interpreting and appraising the literature is fundamental and involves the development of evidence-based dentistry (EBD) skills. Systematic reviews (SRs) of randomized controlled trials (RCTs) are considered to be evidence of the highest level in evaluating the effectiveness of interventions. Furthermore, the assessment of the report of a RCT, as well as a SR, can lead to an estimation of how the study was designed and conducted.

POLICY IMPLICATIONS OF ADJUSTING RANDOMIZED TRIAL DATA FOR ECONOMIC EVALUATIONS: A DEMONSTRATION FROM THE ASCUS-LSIL TRIAGE STUDY

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Campos, Nicole G.; Castle, Philip E.; Schiffman, Mark; Kim, Jane J.

2013-01-01

Background Although the randomized controlled trial (RCT) is widely considered the most reliable method for evaluation of health care interventions, challenges to both internal and external validity exist. Thus, the efficacy of an intervention in a trial setting does not necessarily represent the real-world performance that decision makers seek to inform comparative effectiveness studies and economic evaluations. Methods Using data from the ASCUS-LSIL Triage Study (ALTS), we performed a simplified economic evaluation of age-based management strategies to detect cervical intraepithelial neoplasia grade 3 (CIN3) among women who were referred to the study with low-grade squamous intraepithelial lesions (LSIL). We used data from the trial itself to adjust for 1) potential lead time bias and random error that led to variation in the observed prevalence of CIN3 by study arm, and 2) potential ascertainment bias among providers in the most aggressive management arm. Results We found that using unadjusted RCT data may result in counterintuitive cost-effectiveness results when random error and/or bias are present. Following adjustment, the rank order of management strategies changed for two of the three age groups we considered. Conclusion Decision analysts need to examine study design, available trial data and cost-effectiveness results closely in order to detect evidence of potential bias. Adjustment for random error and bias in RCTs may yield different policy conclusions relative to unadjusted trial data. PMID:22147881

Efficacy of menatetrenone (vitamin K2) against non-vertebral and hip fractures in patients with neurological diseases: meta-analysis of three randomized, controlled trials.

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Iwamoto, Jun; Matsumoto, Hideo; Takeda, Tsuyoshi

2009-01-01

Patients with neurological diseases such as Alzheimer's disease, stroke and Parkinson's disease have been reported to have vitamin K deficiency secondary to malnutrition, which increases the risk of non-vertebral and hip fractures. The purpose of the present study was to clarify the efficacy of menatetrenone (vitamin K(2)) against non-vertebral and hip fractures in patients with neurological diseases. A literature search was conducted on PubMed from January 1995 to July 2008 to identify randomized controlled trials (RCTs) of use of menatetrenone against non-vertebral and hip fractures in patients with neurological diseases. A meta-analysis of all RCTs meeting these criteria was then performed. Three RCTs of patients with Alzheimer's disease (n = 178, mean age 78 years), stroke (n = 99, mean age 66 years) and Parkinson's disease (n = 110, mean age 72 years) met the criteria for meta-analysis. These RCTs did not include placebo controls but did have non-treatment controls. According to the meta-analysis, the overall relative risks (95% confidence intervals) for non-vertebral and hip fractures with menatetrenone treatment compared with non-treatment were 0.13 (0.05, 0.35) and 0.14 (0.05, 0.43), respectively, in patients with neurological diseases. No severe adverse events were reported with menatetrenone treatment. The present meta-analysis of three RCTs suggests that there is efficacy for menatetrenone treatment against non-vertebral and hip fractures among patients with neurological diseases. Further larger placebo-controlled trials are needed to confirm the results of the present study.

Clinical Trials in Veterinary Medicine: A New Era Brings New Challenges.

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Oyama, M A; Ellenberg, S S; Shaw, P A

2017-07-01

Randomized clinical trials (RCTs) are among the most rigorous ways to determine the causal relationship between an intervention and important clinical outcome. Their use in veterinary medicine has become increasingly common, and as is often the case, with progress comes new challenges. Randomized clinical trials yield important answers, but results from these studies can be unhelpful or even misleading unless the study design and reporting are carried out with care. Herein, we offer some perspective on several emerging challenges associated with RCTs, including use of composite endpoints, the reporting of different forms of risk, analysis in the presence of missing data, and issues of reporting and safety assessment. These topics are explored in the context of previously reported veterinary internal medicine studies as well as through illustrative examples with hypothetical data sets. Moreover, many insights germane to RCTs in veterinary internal medicine can be drawn from the wealth of experience with RCTs in the human medical field. A better understanding of the issues presented here can help improve the design, interpretation, and reporting of veterinary RCTs. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Comparison of treatment effect estimates of non-vitamin K antagonist oral anticoagulants versus warfarin between observational studies using propensity score methods and randomized controlled trials

International Nuclear Information System (INIS)

Li, Guowei; Holbrook, Anne; Jin, Yanling; Zhang, Yonghong; Levine, Mitchell A. H.; Mbuagbaw, Lawrence; Witt, Daniel M.; Crowther, Mark; Connolly, Stuart; Chai-Adisaksopha, Chatree; Wan, Zhongxiao; Cheng, Ji; Thabane, Lehana

2016-01-01

Emerging observational studies using propensity score (PS) methods assessed real-world comparative effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with non-valvular atrial fibrillation (AF). We aimed to compare treatment effect estimates of NOACs between PS studies and randomized controlled trials (RCTs). Electronic databases and conference proceedings were searched systematically. Primary outcomes included stroke or systemic embolism (SE) and major bleeding. A random-effects meta-analysis was performed to synthesize the data by pooling the PS- and RCT-derived hazard ratios (HRs) separately. The ratio of HRs (RHR) from the ratio of PS-derived HRs relative to RCT-derived HRs was used to determine whether there was a difference between estimates from PS studies and RCTs. There were 10 PS studies and 5 RCTs included for analysis. No significant difference of treatment effect estimates between the PS studies and RCTs was observed: RHR 1.11, 95 % CI 0.98–1.23 for stroke or SE; RHR 1.07, 95 % CI 0.87–1.34 for major bleeding. A significant association between NOACs and risk of stroke or SE was observed: HR 0.88, 95 % CI 0.83–0.94 for the PS studies; HR 0.79, 95 % CI 0.72–0.87 for the RCTs. However, no relationship between NOACs and risk of major bleeding was found: HR 0.91, 95 % CI 0.79–1.05 for the PS studies; HR 0.85, 95 % CI 0.73–1.00 for the RCTs. In this study, treatment effect estimates of NOACs versus warfarin in patients with non-valvular AF from PS studies are found to be in agreement with those from RCTs.

Dropout from cognitive-behavioral therapy for eating disorders: A meta-analysis of randomized, controlled trials.

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Linardon, Jake; Hindle, Annemarie; Brennan, Leah

2018-05-01

Cognitive-behavioral therapy (CBT) is efficacious for a range of eating disorder presentations, yet premature dropout is one factor that might limit CBTs effectiveness. Improved understanding of dropout from CBT for eating disorders is important. This meta-analysis aimed to study dropout from CBT for eating disorders in randomized controlled trials (RCTs), by (a) identifying the types of dropout definitions applied, (b) providing estimates of dropout, (c) comparing dropout rates from CBT to non-CBT interventions for eating disorders, and (d) testing moderators of dropout. RCTs of CBT for eating disorders that reported rates of dropout were searched. Ninety-nine RCTs (131 CBT conditions) were included. Dropout definitions varied widely across studies. The overall dropout estimate was 24% (95% CI = 22-27%). Diagnostic type, type of dropout definition, baseline symptom severity, study quality, and sample age did not moderate this estimate. Dropout was highest among studies that delivered internet-based CBT and was lowest in studies that delivered transdiagnostic enhanced CBT. There was some evidence that longer treatment protocols were associated with lower dropout. No significant differences in dropout rates were observed between CBT and non-CBT interventions for all eating disorder subtypes. Present study dropout estimates are hampered by the use of disparate dropout definitions applied. This meta-analysis highlights the urgency for RCTs to utilize a standardized dropout definition and to report as much information on patient dropout as possible, so that strategies designed to minimize dropout can be developed, and factors predictive of CBT dropout can be more easily identified. © 2018 Wiley Periodicals, Inc.

Randomized clinical trials in pediatric critical care: Rarely done but desperately needed.

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Randolph, Adrienne G.; Lacroix, Jacques

2002-04-01

OBJECTIVE: To review the benefits and challenges of using the randomized, controlled trial (RCT) study design to evaluate preventive and therapeutic interventions in pediatric critical care medicine. CONCLUSIONS: The RCT design is able to control for many sources of potential bias that other types of study designs cannot. The findings of RCTs often contradict the findings of less rigorous study designs. Before performing an RCT, there must exist a state of clinical equipoise, a sufficient number of eligible patients must be available, and the epidemiology of the disorder in question must be well studied. There are many challenges to performing high-quality RCTs. Studying multiple element support strategies in the critically ill patient population is more complex than studying a single drug therapy. High patient and practice variability and hazy diagnostic definitions can dilute the signal-to-noise ratio. Most interventions in critical care are expected to have a modest or small effect. This markedly increases the requisite sample size. There is a paucity of accepted clinically important measurements of the outcome of critical care, making mortality a common outcome to evaluate with a not-so-common incidence. Developmental issues, the inability to give informed consent, and the failure to perform the appropriate pharmacokinetic and safety studies are additional challenges facing pediatric investigators. Despite these limitations, a good RCT remains the best way to prove that an intervention is working or not. Indeed, RCTs are and will remain the "gold standard" method to estimate the efficacy of a therapeutic or prophylactic intervention.

[Application of Chinese Medical Syndrome Scores in Effectiveness Evaluation: a Critical Appraisal of 240 Randomized Controlled Trials].

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Luo, Hui; Liao, Xing; Wang, Qian

2015-10-01

To explore the role of traditional Chinese medicine (TCM) syndrome scores in effectiveness evaluation of clinical studies. Randomized controlled trials (RCTs) of TCM published in five journals in 2013 were retrieved, including Journal of Traditional Chinese Medicine (JTCM), Chinese Journal of Integrated Traditional and Western Medicine (CJITWM), Chinese Journal of Integrative Medicine (CJIM), Evidence-Based Complementary and Alternative Medicine (ECAM), and American Journal of Chinese Medicine (AJCM). The details of TCM syndrome scores and other relevant factors reported in articles were extracted and analyzed. Descriptive statistics and Chi-square test were used to describe general features of inclusive studies, ratios of reports on CM syndrome scores in each journal, formulated evidence, adopted evaluation rules, important degrees. The difference in the application rate of CM syndrome scores were compared in various diseases, diseases with or without CM syndrome typing, places where clinical studies were implemented, and different journals. A total of 240 RCTs were included, involving 178 published in Chinese version and 62 in English version. CM syndrome scores were used for effectiveness evaluation in 27.1% (65/240) of RCTs, of which, the highest application percentage was 35.3% (18/51) in RCTs published in CJITWM, and the lowest was 0 (0/7) in RCTs published in AJCM. There were 17 methods for grading TCM syndrome scores, of which Guideline for Clinical Research of New Chinese Herbal Medicine was most commonly used. Detailed grading standards for CM syndrome scores were reported in 46 RCTs, and CM syndrome scores were taken as primary or secondary outcomes in 6 RCTs. When describing the percentages of RCTs adopting TCM syndrome score by diseases classification, the lowest was 9.5% (2/21) in mental and behavioral disorders, and the highest was 39.1% (9/23) in endocrine, nutritional, and metabolic diseases. RCTs with TCM syndrome differentiation had a higher

Effects of programmed exercise on depressive symptoms in midlife and older women: A meta-analysis of randomized controlled trials.

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Pérez-López, Faustino R; Martínez-Domínguez, Samuel J; Lajusticia, Héctor; Chedraui, Peter

2017-12-01

To perform a systematic review and meta-analysis to clarify the effect of programmed exercise on depressive symptoms (DSs) in midlife and older women. We carried out a structured search of PubMed-Medline, Web of Science, Scopus, Embase, Cochrane Library and Scielo, from database inception through June 29, 2017, without language restriction. The search included the following terms: "depression", "depressive symptoms", "exercise", "physical activity", "menopause", and "randomized controlled trial" (RCTs) in midlife and older women. The US, UK and Australian Clinical Trials databases were also searched. We assessed randomized controlled trials (RCTs) that compared the effect of exercise for at least 6 weeks versus no intervention on DSs as the outcome (as defined by trial authors). Exercise was classified according to duration as "mid-term exercise intervention" (MTEI; lasting for 12 weeks to 4 months), and "long-term exercise intervention" (LTEI; lasting for 6-12 months). Mean changes (±standard deviations) in DSs, as assessed with different questionnaires, were extracted to calculate Hedges' g and then used as the effect size for meta-analysis. Standardized mean differences (SMDs) of DSs after intervention were pooled using a random-effects model. Eleven publications were included for analysis related to 1943 midlife and older women (age range 44-55 years minimum to 65.5±4.0 maximum), none of whom was using a hormone therapy. Seven MTEIs were associated with a significant reduction in DSs (SMD=-0.44; 95% CI -0.69, -0.18; p=0.0008) compared with controls. The reduction in DSs was also significant in six LTEIs (SMD=- 0.29; 95% CI -0.49; -0.09; p=0.005). Heterogeneity of effects among studies was moderate to high. Less perceived stress and insomnia (after exercise) were also found as secondary outcomes. Exercise of low to moderate intensity reduces depressive symptoms in midlife and older women. Copyright © 2017. Published by Elsevier B.V.

Acupuncture-Related Techniques for Psoriasis: A Systematic Review with Pairwise and Network Meta-Analyses of Randomized Controlled Trials.

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Yeh, Mei-Ling; Ko, Shu-Hua; Wang, Mei-Hua; Chi, Ching-Chi; Chung, Yu-Chu

2017-12-01

There has be a large body of evidence on the pharmacological treatments for psoriasis, but whether nonpharmacological interventions are effective in managing psoriasis remains largely unclear. This systematic review conducted pairwise and network meta-analyses to determine the effects of acupuncture-related techniques on acupoint stimulation for the treatment of psoriasis and to determine the order of effectiveness of these remedies. This study searched the following databases from inception to March 15, 2016: Medline, PubMed, Cochrane Central Register of Controlled Trials, EBSCO (including Academic Search Premier, American Doctoral Dissertations, and CINAHL), Airiti Library, and China National Knowledge Infrastructure. Randomized controlled trials (RCTs) on the effects of acupuncture-related techniques on acupoint stimulation as intervention for psoriasis were independently reviewed by two researchers. A total of 13 RCTs with 1,060 participants were included. The methodological quality of included studies was not rigorous. Acupoint stimulation, compared with nonacupoint stimulation, had a significant treatment for psoriasis. However, the most common adverse events were thirst and dry mouth. Subgroup analysis was further done to confirm that the short-term treatment effect was superior to that of the long-term effect in treating psoriasis. Network meta-analysis identified acupressure or acupoint catgut embedding, compared with medication, and had a significant effect for improving psoriasis. It was noted that acupressure was the most effective treatment. Acupuncture-related techniques could be considered as an alternative or adjuvant therapy for psoriasis in short term, especially of acupressure and acupoint catgut embedding. This study recommends further well-designed, methodologically rigorous, and more head-to-head randomized trials to explore the effects of acupuncture-related techniques for treating psoriasis.

Effect of vitamin E supplementation on serum C-reactive protein level: a meta-analysis of randomized controlled trials.

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Saboori, S; Shab-Bidar, S; Speakman, J R; Yousefi Rad, E; Djafarian, K

2015-08-01

C-reactive protein (CRP), a marker of chronic inflammation, has a major role in the etiology of chronic disease. Vitamin E may have anti-inflammatory effects. However, there is no consensus on the effects of vitamin E supplementation on CRP levels in clinical trials. The aim of this study was to systematically review randomized controlled trials (RCTs) that report on the effects of vitamin E supplementation (α- and γ-tocopherols) on CRP levels. A systematic search of RCTs was conducted on Medline and EMBASE through PubMed, Scopus, Ovid and Science Direct, and completed by a manual review of the literature up to May 2014. Pooled effects were estimated by using random-effects models and heterogeneity was assessed by Cochran's Q and I(2) tests. Subgroup analyses and meta-regression analyses were also performed according to intervention duration, dose of supplementation and baseline level of CRP. Of 4734 potentially relevant studies, only 12 trials met the inclusion criteria with 246 participants in the intervention arms and 249 participants in control arms. Pooled analysis showed a significant reduction in CRP levels of 0.62 mg/l (95% confidence interval = -0.92, -0.31; P vitamin E-treated individuals, with the evidence of heterogeneity across studies. This significant effect was maintained in all subgroups, although the univariate meta-regression analysis showed that the vitamin E supplementation dose, baseline level of CRP and duration of intervention were not the sources of the observed heterogeneity. The results of this meta-analysis suggest that supplementation with vitamin E in the form of either α-tocopherol or γ-tocopherol would reduce serum CRP levels.

Clinical Effects and Safety of Zhi Sou San for Cough: A Meta-Analysis of Randomized Trials

Directory of Open Access Journals (Sweden)

Ningchang Cheng

2017-01-01

Full Text Available Introduction. Zhi Sou San (ZSS, a traditional Chinese prescription, has been widely applied in treating cough. The purpose of this meta-analysis was to evaluate the effectiveness and safety of ZSS for cough. Methods. We searched relevant articles up to 5 March 2017 in seven electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL, MEDLINE, PubMed, Chinese National Knowledge Infrastructure (CNKI, Cqvip Database (VIP, China Biology Medicine disc (CBM, and Wanfang Data. Randomized controlled trials (RCTs were eligible, regardless of blinding. The primary outcome was the total effective rate. Results. Forty-six RCTs with a total of 4007 participants were identified. Compared with western medicine, ZSS significantly improved the total effective rate (OR: 4.45; 95% CI: 3.62–5.47 and the pulmonary function in terms of FEV1 (OR: 0.35; 95% CI: 0.24–0.46 and decreased the adverse reactions (OR: 0.05; 95% CI: 0.02–0.01 and the recurrence rate (OR: 0.30; 95% CI: 0.16–0.57. However, there was no significant improvement in the cough symptom score comparing ZSS with western medicine. Conclusions. This meta-analysis shows that ZSS has significant additional benefits and relative safety in treating cough. However, more rigorously designed investigations and studies, with large sample sizes, are needed because of the methodological flaws and low quality of the included trials in this meta-analysis.

Effectiveness and implementation aspects of interventions for preventing falls in elderly people in long-term care facilities: a systematic review of RCTs.

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Neyens, Jacques C; van Haastregt, Jolanda C; Dijcks, Béatrice P; Martens, Mark; van den Heuvel, Wim J; de Witte, Luc P; Schols, Jos M

2011-07-01

There is extensive literature on interventions to prevent or reduce falls in elderly people. These findings, however, were based mainly on studies of community-living persons. The primary aim of the present study was to report the effectiveness and implementation aspects of interventions aimed at reducing falls in elderly residents in long-term care facilities: a systematic review of randomized controlled trials (RCTs). MEDLINE, EMBASE, CINAHL, and hand searching of reference lists of included RCTs. RCTs that assessed fall incidents (falls, fallers, recurrent fallers, fall-related injuries) among elderly residents in long-term care facilities were included in this narrative review. Two independent reviewers abstracted data: general program characteristics (setting, population, intervention program) and outcomes, detailed program characteristics (assessment, intervention content, individually tailored, multidisciplinary), and implementation aspects (feasibility, implications for practice). The CONSORT Statement 2001 Checklist was used regarding the quality of reporting RCTs. Twenty trials met the inclusion criteria. Seven trials, 4 multifactorial and 3 monofactorial, showed a significant reduction in the fall rate, the percentage of recurrent fallers, or both the fall rate and the percentage of persons sustaining femoral fractures. The positive effective programs were as follows: a comprehensive structured individual assessment with specific safety recommendations; a multidisciplinary program including general strategies tailored to the setting and strategies tailored specifically to residents; a multifaceted intervention including education, environmental adaptation, balance, resistance training, and hip protector; calcium plus vitamin D supplementation; vitamin D supplementation; a clinical medication review; and a multifactorial intervention (fall risk evaluation, specific and general interventions). In general, because of the limited number of included trials

Efficacy of Aloe Vera Supplementation on Prediabetes and Early Non-Treated Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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Zhang, Yiyi; Liu, Wen; Liu, Dan; Zhao, Tieyun; Tian, Haoming

2016-06-23

The aim of this study was to evaluate evidence for the efficacy of aloe vera on managing prediabetes and early non-treated diabetes mellitus. We performed a systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials until 28 January 2016. A total of five randomized controlled trials (RCTs) involving 415 participants were included. Compared with the controls, aloe vera supplementation significantly reduced the concentrations of fasting blood glucose (FBG) (p = 0.02; weighed mean difference [WMD]: -30.05 mg/dL; 95% confidence interval [CI]: -54.87 to -5.23 mg/dL), glycosylated hemoglobin A1c (HbA1c) (p Aloe vera was superior to placebo in increasing serum high density lipoprotein-cholesterol (HDL-C) levels (p = 0.04). Only one adverse event was reported. The evidence from RCTs showed that aloe vera might effectively reduce the levels of FBG, HbA1c, triglyceride, TC and LDL-C, and increase the levels of HDL-C on prediabetes and early non-treated diabetic patients. Limited evidence exists about the safety of aloe vera. Given the small number and poor quality of RCTs included in the meta-analysis, these results are inconclusive. A large-scale, well-designed RCT is needed to further address this issue.

Using Guasha to treat musculoskeletal pain: A systematic review of controlled clinical trials

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Choi Sun-Mi

2010-01-01

Full Text Available Abstract Background Guasha is a therapeutic method for pain management using tools to scrape or rub the surface of the body to relieve blood stagnation. This study aims to systematically review the controlled clinical trials on the effectiveness of using Guasha to treat musculoskeletal pain. Methods We searched 11 databases (without language restrictions: MEDLINE, Allied and Complementary Medicine (AMED, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL, Korean Studies Information (KSI, DBPIA, Korea Institute of Science and Technology Information (KISTI, KoreaMed, Research Information Service System (RISS, China National Knowledge Infrastructure (CNKI and the Cochrane Library. The search strategy was Guasha (OR scraping AND pain. Risk of bias was assessed with the Cochrane criteria (i.e. sequence generation, blinding, incomplete outcome measures and allocation concealment. Results Five randomized controlled trials (RCTs and two controlled clinical trials (CCTs were included in the present study. Two RCTs compared Guasha with acupuncture in terms of effectiveness, while the other trials compared Guasha with no treatment (1 trial, acupuncture (4 trials, herbal injection (1 trial and massage or electric current therapy (1 trial. While two RCTs suggested favorable effects of Guasha on pain reduction and response rate, the quality of these RCTs was poor. One CCT reported beneficial effects of Guasha on musculoskeletal pain but had low methodological quality. Conclusion Current evidence is insufficient to show that Guasha is effective in pain management. Further RCTs are warranted and methodological quality should be improved.

Prolonged Cardiac Monitoring to Detect Atrial Fibrillation after Cryptogenic Stroke or Transient Ischemic Attack: A Meta-Analysis of Randomized Controlled Trials.

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Dahal, Khagendra; Chapagain, Bikas; Maharjan, Raju; Farah, Hussam W; Nazeer, Ayesha; Lootens, Robert J; Rosenfeld, Alan

2016-07-01

The cause of ischemic stroke or transient ischemic attack (TIA) remains unclear after initial cardiac monitoring in approximately one-third of patients. Randomized controlled trials (RCTs) showed that the prolonged cardiac monitoring of patients with cryptogenic stroke or TIA increased detection of atrial fibrillation (AF). We aimed to perform a meta-analysis of all RCTs that evaluated the prolonged monitoring ≥7 days in patients with cryptogenic stroke or TIA. We searched PubMed, EMBASE, Cochrane CENTRAL, and relevant references for RCTs without language restriction (inception through December 2014) and performed meta-analysis using random effects model. Detection of AF, use of anticoagulation at follow-up, recurrent stroke or TIA, and mortality were major outcomes. Four RCTs with 1149 total patients were included in the meta-analysis. Prolonged cardiac monitoring ≥7 days compared to shorter cardiac monitoring of ≤48 hours duration increased the detection of AF (≥30 seconds duration) in patients after cryptogenic stroke or TIA (13.8% vs. 2.5%; odds ratio [OR], 6.4; 95% confidence interval [CI], 3.50-11.73; P vs. 5.2%; 5.68[3.3-9.77]; P stroke or TIA (0.78[0.40-1.55]; P = 0.48; I(2) , 0%) and mortality (1.33[0.29-6.00]; P = 0.71; I(2) , 0%] were observed between two strategies. Prolonged cardiac monitoring improves detection of atrial fibrillation and anti-coagulation use after cryptogenic stroke or TIA and therefore should be considered instead of shorter duration of cardiac monitoring. © 2015 Wiley Periodicals, Inc.

FFR-guided multivessel stenting reduces urgent revascularization compared with infarct-related artery only stenting in ST-elevation myocardial infarction: A meta-analysis of randomized controlled trials.

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Gupta, Ankur; Bajaj, Navkaranbir S; Arora, Pankaj; Arora, Garima; Qamar, Arman; Bhatt, Deepak L

2018-02-01

Randomized controlled trials (RCTs) have shown fractional flow reserve-guided (FFR) multivessel stenting to be superior to infarct-related artery (IRA) only stenting in patients with ST-elevation myocardial infarction (STEMI) and multivessel disease. This effect was mainly driven by a reduction in overall repeat revascularization. However, the ability to assess the effect of this strategy on urgent revascularization or reinfarction was underpowered in individual trials. We searched Pubmed, EMBASE, Cochrane CENTRAL, and Web of Science for RCTs of FFR-guided multivessel stenting versus IRA-only stenting in STEMI with multivessel disease. The outcomes of interest were death, reinfarction, urgent, and non-urgent repeat revascularization. Risk ratios (RR) were pooled using the DerSimonian and Laird random-effects model. After review of 786 citations, 2 RCTs were included. The pooled results demonstrated a significant reduction in the composite of death, reinfarction, or revascularization in the FFR-guided multivessel stenting group versus IRA-only stenting group (RR [95%, Confidence Interval]: 0.49 [0.33-0.72], p<0.001). This risk reduction was driven mainly by a reduction in repeat revascularization, both urgent (0.41 [0.24-0.71], p=0.002) and non-urgent revascularization (0.31 [0.19-0.50], p<0.001). Pooled RR for reinfarction was lower in the FFR-guided strategy, but was not statistically significant (0.71[0.39-1.31], p=0.28). This systematic review and meta-analysis suggests that a strategy of FFR-guided multivessel stenting in STEMI patients reduces not only overall repeat revascularization but also urgent revascularization. The effect on reinfarction needs to be evaluated in larger trials. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Sucralfate versus histamine 2 receptor antagonists for stress ulcer prophylaxis in adult critically ill patients: A meta-analysis and trial sequential analysis of randomized trials.

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Alquraini, Mustafa; Alshamsi, Fayez; Møller, Morten Hylander; Belley-Cote, Emilie; Almenawer, Saleh; Jaeschke, Roman; MacLaren, Robert; Alhazzani, Waleed

2017-08-01

To determine the impact of using sucralfate versus H2RAs for SUP on patient important outcomes. We searched CENTRAL, MEDLINE, EMBASE, ACPJC, clinical trials registries, and conference proceedings through June 2016 for randomized controlled trials (RCTs) comparing sucralfate to H2RAs for SUP in adult critically ill patients. 21 RCTs enrolling 3121 patients met inclusion criteria. There was no significant difference between sucralfate compared to H2RAs in the risk of clinically important GI bleeding (risk ratio [RR] 1.19; 95% CI [confidence interval] 0.79, 1.80; P=0.42; I 2 =0%; low quality evidence). However, there was a statistically significant lower risk of ICU acquired pneumonia with sucralfate compared to H2RAs (RR 0.84; 95% CI 0.72, 0.98; P=0.03; I 2 =0%; moderate quality evidence). Sucralfate did not significantly affect the risk of death (RR 0.95; 95% CI 0.82, 1.10; P=0.51; I 2 =0%; high quality evidence), or duration of ICU stay in days (mean difference-0.39; 95% CI [-1.12, 0.34]; P=0.29; I 2 =0%; moderate quality evidence). Trial sequential analysis adjusted estimates were consistent with conventional estimates. Moderate quality evidence suggests that sucralfate reduced ICU acquired pneumonia compared to H2RAs in adult critically ill patients, with no significant impact on GI bleeding or death. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of pomegranate juice on blood pressure: A systematic review and meta-analysis of randomized controlled trials.

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Sahebkar, Amirhossein; Ferri, Claudio; Giorgini, Paolo; Bo, Simona; Nachtigal, Petr; Grassi, Davide

2017-01-01

Punica granatum L. (Pomegranate) has been claimed to provide several health benefits. Pomegranate juice is a polyphenol-rich fruit juice with high antioxidant capacity. Several studies suggested that pomegranate juice can exert antiatherogenic, antioxidant, antihypertensive, and anti-inflammatory effects. Nevertheless, the potential cardioprotective benefits of pomegranate juice deserve further clinical investigation. To systematically review and meta-analyze available evidence from randomized placebo-controlled trials (RCTs) investigating the effects of pomegranate juice consumption and blood pressure (BP). A comprehensive literature search in Medline and Scopus was carried out to identify eligible RCTs. A meta-analysis of eligible studies was performed using a random-effects model. Quality assessment, sensitivity analysisand publication bias evaluations were conducted using standard methods. Quantitative data synthesis from 8 RCTs showed significant reductions in both systolic [weighed mean difference (WMD): -4.96mmHg, 95% CI: -7.67 to -2.25, pjuice consumption. Effects on SBP remained stable to sensitivity analyses. Pomegranate juice reduced SBP regardless of the duration (>12 wks: WMD=-4.36mmHg, 95% CI: -7.89 to -0.82, p=0.016) and 240cc: WMD=-3.62mmHg, 95% CI: -6.62 to -0.63, p=0.018) and juice per day) whereas doses >240cc provided a borderline significant effect in reducing DBP. The present meta-analysis suggests consistent benefits of pomegranate juice consumption on BP. This evidence suggests it may be prudent to include this fruit juice in a heart-healthy diet. Copyright © 2016 Elsevier Ltd. All rights reserved.

A critical appraisal of the reporting quality of published randomized controlled trials in the fall injuries.

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Asghari Jafarabadi, Mohammad; Sadeghi-Bazrgani, Homayoun; Dianat, Iman

2018-06-01

To evaluate the quality of reporting in published randomized controlled trials (RTCs) in the field of fall injuries. The 188 RTCs published between 2001 and 2011, indexed in EMBASE and Medline databases were extracted through searching by appropriate keywords and EMTree classification terms. The evaluation trustworthiness was assured through parallel evaluations of two experts in epidemiology and biostatistics. About 40%-75% of papers had problems in reporting random allocation method, allocation concealment, random allocation implementation, blinding and similarity among groups, intention to treat and balancing benefits and harms. Moreover, at least 10% of papers inappropriately/not reported the design, protocol violations, sample size justification, subgroup/adjusted analyses, presenting flow diagram, drop outs, recruitment time, baseline data, suitable effect size on outcome, ancillary analyses, limitations and generalizability. Considering the shortcomings found and due to the importance of the RCTs for fall injury prevention programmes, their reporting quality should be improved.

The metabolic and endocrine response and health implications of consuming sugar-sweetened beverages: findings from recent randomized controlled trials.

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Rippe, James M

2013-11-01

Fructose-containing sugars, including fructose itself, high fructose corn syrup (HFCS), and sucrose have engendered considerable controversy. The effects of HFCS and sucrose in sugar-sweetened beverages, in particular, have generated intense scientific debate that has spilled over to the public. This controversy is related to well-known differences in metabolism between fructose and glucose in the liver. In addition, research studies have often been conducted comparing pure fructose and pure glucose even though neither is consumed to any appreciable degree in isolation in the human diet. Other evidence has been drawn from animal studies and epidemiologic or cohort studies. Few randomized controlled trials (RCTs) have compared HFCS with sucrose (the 2 sugars most commonly consumed in the human diet) at dosage amounts within the normal human consumption range. This review compares results of recently concluded RCTs with other forms of evidence related to fructose, HFCS, and sucrose. We conclude that great caution must be used when suggesting adverse health effects of consuming these sugars in the normal way they are consumed and at the normal amounts in the human diet, because RCTs do not support adverse health consequences at these doses when employing these sugars.

Radioiodine therapy versus antithyroid drugs in Graves' disease: a meta-analysis of randomized controlled trials

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Qin, Lan

2016-01-01

Objective: This meta-analysis was performed to compare radioiodine therapy with antithyroid drugs in terms of clinical outcomes, including development or worsening of ophthalmopathy, hyperthyroid cure rate, hypothyroidism, relapse rate and adverse events. Methods: Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed and National Knowledge Infrastructure, China, were systematically reviewed to compare the effects of radioiodine therapy with antithyroid drugs in patients with Graves' disease. Results were expressed as risk ratio with 95% confidence intervals (CIs) and weighted mean differences with 95% CIs. Pooled estimates were performed using a fixed-effects model or random-effects model, depending on the heterogeneity among studies. Results: 17 RCTs involving 4024 patients met the inclusion criteria and were included. Results showed that radioiodine treatment has increased risk in new ophthalmopathy, development or worsening of ophthalmopathy and hypothyroidism. Whereas, compared with antithyroid drugs, radioiodine treatment seems to have a higher hyperthyroid cure rate, lower recurrence rate and lower incidence of adverse events. Conclusion: Radioiodine therapy is associated with a higher hyperthyroid cure rate and lower relapse rate compared with antithyroid drugs. However, it also increases the risk of ophthalmopathy and hypothyroidism. Advances in knowledge: Considering that antithyroid drug treatment can be associated with unsatisfactory control of hyperthyroidism, we would recommend radioiodine therapy as the treatment of choice for patients with Graves' disease. PMID:27266544

Citation networks of related trials are often disconnected: implications for bidirectional citation searches.

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Robinson, Karen A; Dunn, Adam G; Tsafnat, Guy; Glasziou, Paul

2014-07-01

Reports of randomized controlled trials (RCTs) should set findings within the context of previous research. The resulting network of citations would also provide an alternative search method for clinicians, researchers, and systematic reviewers seeking to base decisions on all available evidence. We sought to determine the connectedness of citation networks of RCTs by examining direct (referenced trials) and indirect (through references of referenced trials, etc) citation of trials to one another. Meta-analyses were used to create citation networks of RCTs addressing the same clinical questions. The primary measure was the proportion of networks where following citation links between RCTs identifies the complete set of RCTs, forming a single connected citation group. Other measures included the number of disconnected groups (islands) within each network, the number of citations in the network relative to the maximum possible, and the maximum number of links in the path between two connected trials (a measure of indirectness of citations). We included 259 meta-analyses with a total of 2,413 and a median of seven RCTs each. For 46% (118 of 259) of networks, the RCTs formed a single connected citation group-one island. For the other 54% of networks, where at least one RCT group was not cited by others, 39% had two citation islands and 4% (10 of 257) had 10 or more islands. On average, the citation networks had 38% of the possible citations to other trials (if each trial had cited all earlier trials). The number of citation islands and the maximum number of citation links increased with increasing numbers of trials in the network. Available evidence to answer a clinical question may be identified by using network citations created with a small initial corpus of eligible trials. However, the number of islands means that citation networks cannot be relied on for evidence retrieval. Copyright © 2014 Elsevier Inc. All rights reserved.

The Efficacy of Eye Movement Desensitization and Reprocessing in Children and Adults Who Have Experienced Complex Childhood Trauma: A Systematic Review of Randomized Controlled Trials.

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Chen, Runsen; Gillespie, Amy; Zhao, Yanhui; Xi, Yingjun; Ren, Yanping; McLean, Loyola

2018-01-01

Background: Survivors of complex childhood trauma (CT) such as sexual abuse show poorer outcomes compared to single event trauma survivors. A growing number of studies investigate Eye Movement Desensitization and Reprocessing (EMDR) treatment for posttraumatic stress disorder (PTSD), but no systematic reviews have focused on EMDR treatment for CT as an intervention for both adults and children. This study therefore systematically reviewed all randomized controlled trials (RCTs) evaluating the effect of EMDR on PTSD symptoms in adults and children exposed to CT. Methods: Databases including PubMed, Web of Science, and PsycINFO were searched in October 2017. Randomized controlled trials which recruited adult and children with experience of CT, which compared EMDR to alternative treatments or control conditions, and which measured PTSD symptoms were included. Study methodology quality was evaluated with Platinum Standard scale. Results: Six eligible RCTs of 251 participants were included in this systematic review. The results indicated that EMDR was associated with reductions in PTSD symptoms, depression and/or anxiety both post-treatment and at follow-up compared with all other alternative therapies (cognitive behavior therapy, individual/group therapy and fluoxetine) and control treatment (pill placebo, active listening, EMDR delayed treatment, and treatment as usual). However, studies suffered from significant heterogeneity in study populations, length of EMDR treatment, length of follow-up, comparison groups, and outcome measures. One study had a high risk of bias. Discussion: This systematic review suggests that there is growing evidence to support the clinical efficacy of EMDR in treating CT in both children and adults. However, conclusions are limited by the small number of heterogenous trials. Further RCTs with standardized methodologies, as well as studies addressing real world challenges in treating CT are required.

The Efficacy of Eye Movement Desensitization and Reprocessing in Children and Adults Who Have Experienced Complex Childhood Trauma: A Systematic Review of Randomized Controlled Trials

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Runsen Chen

2018-04-01

Full Text Available Background: Survivors of complex childhood trauma (CT such as sexual abuse show poorer outcomes compared to single event trauma survivors. A growing number of studies investigate Eye Movement Desensitization and Reprocessing (EMDR treatment for posttraumatic stress disorder (PTSD, but no systematic reviews have focused on EMDR treatment for CT as an intervention for both adults and children. This study therefore systematically reviewed all randomized controlled trials (RCTs evaluating the effect of EMDR on PTSD symptoms in adults and children exposed to CT.Methods: Databases including PubMed, Web of Science, and PsycINFO were searched in October 2017. Randomized controlled trials which recruited adult and children with experience of CT, which compared EMDR to alternative treatments or control conditions, and which measured PTSD symptoms were included. Study methodology quality was evaluated with Platinum Standard scale.Results: Six eligible RCTs of 251 participants were included in this systematic review. The results indicated that EMDR was associated with reductions in PTSD symptoms, depression and/or anxiety both post-treatment and at follow-up compared with all other alternative therapies (cognitive behavior therapy, individual/group therapy and fluoxetine and control treatment (pill placebo, active listening, EMDR delayed treatment, and treatment as usual. However, studies suffered from significant heterogeneity in study populations, length of EMDR treatment, length of follow-up, comparison groups, and outcome measures. One study had a high risk of bias.Discussion: This systematic review suggests that there is growing evidence to support the clinical efficacy of EMDR in treating CT in both children and adults. However, conclusions are limited by the small number of heterogenous trials. Further RCTs with standardized methodologies, as well as studies addressing real world challenges in treating CT are required.

Effects of Statin Treatment on Inflammation and Cardiac Function in Heart Failure: An Adjusted Indirect Comparison Meta-Analysis of Randomized Trials.

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Bonsu, Kwadwo Osei; Reidpath, Daniel Diamond; Kadirvelu, Amudha

2015-12-01

Statins are known to prevent heart failure (HF). However, it is unclear whether statins as class or type (lipophilic or hydrophilic) improve outcomes of established HF. The current meta-analysis was performed to compare the treatment effects of lipophilic and hydrophilic statins on inflammation and cardiac function in HF. Outcomes were indicators of cardiac function [changes in left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP)] and inflammation [changes in highly sensitive C-reactive protein (hsCRP) and interluekin-6 (IL-6)]. We conducted a search of PubMed, EMBASE, and the Cochrane databases until December 31, 2014 for randomized control trials (RCTs) of statin versus placebo in patients with HF. RCTs with their respective extracted information were dichotomized into statin type evaluated and analyzed separately. Outcomes were pooled with random effect approach, producing standardized mean differences (SMD) for each statin type. Using these pooled estimates, we performed adjusted indirect comparisons for each outcome. Data from 6214 patients from 19 trials were analyzed. Lipophilic statin was superior to hydrophilic statin treatment regarding follow-up LVEF (SMD, 4.54; 95% CI, 4.16-4.91; P statin produces greater treatment effects on cardiac function and inflammation compared with hydrophilic statin in patients with HF. Until data from adequately powered head-to-head trial of the statin types are available, our meta-analysis brings clinicians and researchers a step closer to the quest on which statin--lipophilic or hydrophilic--is associated with better outcomes in HF. © 2015 John Wiley & Sons Ltd.

[Systematic review on methodology of randomized controlled trials of post-marketing Chinese patent drugs for treatment of type 2 diabetes].

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Ma, Li-xin; Wang, Yu-yi; Li, Xin-xue; Liu, Jian-ping

2012-03-01

Randomized controlled trial (RCT) is considered as the gold standard for the efficacy assessment of medicines. With the increasing number of Chinese patent drugs for treatment of type 2 diabetes, the methodology of post-marketing RCTs evaluating the efficacy and specific effect has become more important. To investigate post-marketing Chinese patent drugs for treatment of type 2 diabetes, as well as the methodological quality of post-marketing RCTs. Literature was searched from the books of Newly Compiled Traditional Chinese Patent Medicine and Chinese Pharmacopeia, the websites of the State Food and Drug Administration and the Ministry of Human Resources and Social Security of the People's Republic of China, China National Knowledge Infrastructure Database, Chongqing VIP Chinese Science and Technology Periodical Database, Chinese Biomedical Database (SinoMed) and Wanfang Data. The time period for searching ran from the commencement of each database to August 2011. RCTs of post-marketing Chinese patent drugs for treatment of type 2 diabetes with intervention course no less than 3 months. Two authors independently evaluated the research quality of the RCTs by the checklist of risk bias assessment and the data collection forms based on the CONSORT Statement. Independent double data-extraction was performed. The authors identified a total of 149 Chinese patent drugs for treatment of type 2 diabetes. According to different indicative syndromes, the Chinese patent drugs can be divided into the following types, namely, yin deficiency and interior heat (n=48, 32%), dual deficiency of qi and yin (n=58, 39%) and dual deficiency of qi and yin combined with blood stasis (n=22, 15%). A total of 41 RCTs meeting the inclusion criteria were included. Neither multicenter RCTs nor endpoint outcome reports were found. Risk bias analysis showed that 81% of the included studies reported randomization for grouping without sequence generation, 98% of these studies did not report

A systematic review of randomized trials for the treatment of burning mouth syndrome.

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Kisely, Steve; Forbes, Malcolm; Sawyer, Emily; Black, Emma; Lalloo, Ratilal

2016-07-01

Burning mouth syndrome (BMS) is characterized by burning of the oral mucosa in the absence of underlying dental or medical causes. The results of previous systematic reviews have generally been equivocal. However, findings for most interventions are based on searches of 5-10years ago. This study therefore updates previous searches of randomized controlled trials (RCTs) for pain as assessed by Visual Analogue Scales (VAS). Secondary outcomes included quality of life, mood, taste and salivary flow. A search of MEDLINE and Embase up to 2016. 24 RCTs were identified. Meta-analyses were impossible because of wide variations in study method and quality. The commonest interventions were alpha-lipoic acid (ALA) (8 comparisons), capsaicin or an analogue (4 comparisons), clonazepam (3 comparisons) and psychotherapy (2 comparisons). ALA and capsaicin led to significantly greater improvements in VAS (4 studies each), as did clonazepam (all 3 studies), at up to two month follow-up. However, capsaicin led to prominent dyspepsia. Psychotherapy significantly improved outcomes in one study at two and 12month follow-up. Catauma and tongue-protectors also showed promise (one study each). There were no significant differences in any of the secondary outcomes except in the one study of tongue protectors. At least in some studies and for some outcomes, ALA, clonazepam, capsaicin and psychotherapy may show modest benefit in the first two months. However, these conclusions are limited by generally short follow-up periods, high study variability and low participant numbers. Further RCTs with follow-up of at least 12months are indicated. Copyright © 2016 Elsevier Inc. All rights reserved.

The influence of anti-infective periodontal treatment on C-reactive protein: a systematic review and meta-analysis of randomized controlled trials.

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Ryan T Demmer

Full Text Available Periodontal infections are hypothesized to increase the risk of adverse systemic outcomes through inflammatory mechanisms. The magnitude of effect, if any, of anti-infective periodontal treatment on systemic inflammation is unknown, as are the patient populations most likely to benefit. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs to test the hypothesis that anti-infective periodontal treatment reduces systemic c-reactive protein (CRP.MEDLINE, EMBASE, CENTRAL and CINAHL databases were searched using sensitivity-enhancing search terms. Eligible RCTs enrolled patients with periodontal infection, compared a clearly defined anti-infective periodontal intervention (experimental group to an "inactive control" (no periodontal intervention or to an "active control" (lower treatment intensity than the experimental group. Mean differences in final CRP values at the earliest post-treatment time point (typically 1-3 months between experimental and control groups were analyzed using random-effects regression. Among 2,753 possible studies 20 were selected, which included 2,561 randomized patients(median=57. Baseline CRP values were >3.0 mg/L in 40% of trials. Among studies with a control group receiving no treatment, the mean difference in CRP final values among experimental treatment vs. control groups was -0.37 mg/L [95%CI=-0.64, -0.11], (P=0.005, favoring experimental treatment. Trials for which the experimental group received antibiotics had stronger effects (P for interaction=0.03 and the mean difference in CRP final values among experimental treatment vs. control was -0.75 mg/L [95%CI=-1.17,-0.33]. No treatment effect was observed among studies using an active treatment comparator. Treatment effects were stronger for studies that included patients with co-morbidities vs. studies that included "systemically healthy" patients, although the interaction was not significant (P=0.48.Anti-infective periodontal

Long-acting insulin analogues for type 1 diabetes: An overview of systematic reviews and meta-analysis of randomized controlled trials.

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Laranjeira, Fernanda O; de Andrade, Keitty R C; Figueiredo, Ana C M G; Silva, Everton N; Pereira, Mauricio G

2018-01-01

The comparison between long acting insulin analogues (LAIA) and human insulin (NPH) has been investigated for decades, with many randomized controlled trials (RCTs) and systematic reviews giving mixed results. This overlapping and contradictory evidence has increased uncertainty on coverage decisions at health systems level. To conduct an overview of systematic reviews and update existing reviews, preparing new meta-analysis to determine whether LAIA are effective for T1D patients compared to NPH. We identified systematic reviews of RCTs that evaluated the efficacy of LAIA glargine or detemir, compared to NPH insulin for T1D, assessing glycated hemoglobin (A1C) and hypoglycemia. Data sources included Pubmed, Cochrane Library, EMBASE and hand-searching. The methodological quality of studies was independently assessed by two reviewers, using AMSTAR and Jadad scale. We found 11 eligible systematic reviews that contained a total of 25 relevant clinical trials. Two reviewers independently abstracted data. We found evidence that LAIA are efficacious compared to NPH, with estimates showing a reduction in nocturnal hypoglycemia episodes (RR 0.66; 95% CI 0.57; 0.76) and A1C (95% CI 0.23; 0.12). No significance was found related to severe hypoglycemia (RR 0.94; 95% CI 0.71; 1.24). This study design has allowed us to carry out the most comprehensive assessment of RCTs on this subject, filling a gap in diabetes research. Our paper addresses a question that is important not only for decision makers but also for clinicians.

Exercise for depression in older adults: a meta-analysis of randomized controlled trials adjusting for publication bias

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Felipe B. Schuch

Full Text Available Objective: To evaluate the antidepressant effects of exercise in older adults, using randomized controlled trial (RCT data. Methods: We conducted a meta-analysis of exercise in older adults, addressing limitations of previous works. RCTs of exercise interventions in older people with depression (≥ 60 years comparing exercise vs. control were eligible. A random-effects meta-analysis calculating the standardized mean difference (SMD (95% confidence interval [95%CI], meta-regressions, and trim, fill, and fail-safe number analyses were conducted. Results: Eight RCTs were included, representing 138 participants in exercise arms and 129 controls. Exercise had a large and significant effect on depression (SMD = -0.90 [95%CI -0.29 to -1.51], with a fail-safe number of 71 studies. Significant effects were found for 1 mixed aerobic and anaerobic interventions, 2 at moderate intensity, 3 that were group-based, 4 that utilized mixed supervised and unsupervised formats, and 5 in people without other clinical comorbidities. Conclusion: Adjusting for publication bias increased the beneficial effects of exercise in three subgroup analysis, suggesting that previous meta-analyses have underestimated the benefits of exercise due to publication bias. We advocate that exercise be considered as a routine component of the management of depression in older adults.

Effect of Replacing Animal Protein with Plant Protein on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Effie Viguiliouk

2015-12-01

Full Text Available Previous research on the effect of replacing sources of animal protein with plant protein on glycemic control has been inconsistent. We therefore conducted a systematic review and meta-analysis of randomized controlled trials (RCTs to assess the effect of this replacement on glycemic control in individuals with diabetes. We searched MEDLINE, EMBASE, and Cochrane databases through 26 August 2015. We included RCTs ≥ 3-weeks comparing the effect of replacing animal with plant protein on HbA1c, fasting glucose (FG, and fasting insulin (FI. Two independent reviewers extracted relevant data, assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD with 95% confidence intervals (CIs. Heterogeneity was assessed (Cochran Q-statistic and quantified (I2-statistic. Thirteen RCTs (n = 280 met the eligibility criteria. Diets emphasizing a replacement of animal with plant protein at a median level of ~35% of total protein per day significantly lowered HbA1c (MD = −0.15%; 95%-CI: −0.26, −0.05%, FG (MD = −0.53 mmol/L; 95%-CI: −0.92, −0.13 mmol/L and FI (MD = −10.09 pmol/L; 95%-CI: −17.31, −2.86 pmol/L compared with control arms. Overall, the results indicate that replacing sources of animal with plant protein leads to modest improvements in glycemic control in individuals with diabetes. Owing to uncertainties in our analyses there is a need for larger, longer, higher quality trials. Trial Registration: ClinicalTrials.gov registration number: NCT02037321.

Effect of inulin-type fructans on blood lipid profile and glucose level: a systematic review and meta-analysis of randomized controlled trials.

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Liu, F; Prabhakar, M; Ju, J; Long, H; Zhou, H-W

2017-01-01

This systematic review and meta-analysis was performed to assess the effects of inulin-type fructans (ITF) on human blood lipids and glucose homeostasis associated with metabolic abnormalities, including dyslipidemia, overweight or obesity, and type-2 diabetes mellitus (T2DM). The MEDLINE, EMBASE and Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) before January 2016. Human trials that investigated the effects of ITF supplementation on the lipid profile, fasting glucose and insulin were included using Review Manager 5.3. Twenty RCTs with 607 adult participants were included in this systematic review and meta-analysis. In the overall analysis, the supplementation of ITF reduced only the low density lipoprotein-cholesterol (LDL-c) (mean difference (MD): -0.15; 95% confidence interval (CI): -0.29, -0.02; P=0.03) without affecting the other endpoints. Within the T2DM subgroup analysis, ITF supplementation was positively associated with a decreased fasting insulin concentration (MD: -4.01; 95% CI: -5.92, -2.09; Pglucose tendency was identified only in the T2DM subgroup (MD: -0.42; 95% CI: -0.90, 0.06; P=0.09). There was a potential publication bias, and few trials were available for the T2DM subgroup analysis. In summary, the use of ITF may have benefits for LDL-c reduction across all study populations, whereas HDL-c improvement and glucose control were demonstrated only in the T2DM subgroup. Thus, additional, well-powered, long-term, randomized clinical trials are required for a definitive conclusion. Overall, ITF supplementation may provide a novel direction for improving the lipid profile and glucose metabolism.

The effect of magnesium supplementation on blood pressure in individuals with insulin resistance, prediabetes, or noncommunicable chronic diseases: a meta-analysis of randomized controlled trials.

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Dibaba, Daniel T; Xun, Pengcheng; Song, Yiqing; Rosanoff, Andrea; Shechter, Michael; He, Ka

2017-09-01

Background: To our knowledge, the effect of magnesium supplementation on blood pressure (BP) in individuals with preclinical or noncommunicable diseases has not been previously investigated in a meta-analysis, and the findings from randomized controlled trials (RCTs) have been inconsistent. Objective: We sought to determine the pooled effect of magnesium supplementation on BP in participants with preclinical or noncommunicable diseases. Design: We identified RCTs that were published in English before May 2017 that examined the effect of magnesium supplementation on BP in individuals with preclinical or noncommunicable diseases through PubMed, ScienceDirect, Cochrane, clinicaltrials.gov, SpringerLink, and Google Scholar databases as well as the reference lists from identified relevant articles. Random- and fixed-effects models were used to estimate the pooled standardized mean differences (SMDs) with 95% CIs in changes in BP from baseline to the end of the trial in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) between the magnesium-supplementation group and the control group. Results: Eleven RCTs that included 543 participants with follow-up periods that ranged from 1 to 6 mo (mean: 3.6 mo) were included in this meta-analysis. The dose of elemental magnesium that was used in the trials ranged from 365 to 450 mg/d. All studies reported BP at baseline and the end of the trial. The weighted overall effects indicated that the magnesium-supplementation group had a significantly greater reduction in both SBP (SMD: -0.20; 95% CI: -0.37, -0.03) and DBP (SMD: -0.27; 95% CI: -0.52, -0.03) than did the control group. Magnesium supplementation resulted in a mean reduction of 4.18 mm Hg in SBP and 2.27 mm Hg in DBP. Conclusion: The pooled results suggest that magnesium supplementation significantly lowers BP in individuals with insulin resistance, prediabetes, or other noncommunicable chronic diseases. © 2017 American Society for Nutrition.

Omalizumab for severe allergic asthma in clinical trials and real-life studies: what we know and what we should address.

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Caminati, Marco; Senna, Gianenrico; Guerriero, Massimo; Dama, Anna Rita; Chieco-Bianchi, Fulvia; Stefanizzi, Giorgia; Montagni, Marcello; Ridolo, Erminia

2015-04-01

Randomized clinical trials (RCTs) are the gold standard for the assessment of any therapeutic intervention. Real-life (R-L) studies are needed to verify the provided results beyond the experimental setting. This review aims at comparing RCTs and R-L studies on omalizumab in adult severe allergic asthma, in order to highlight the concurring results and the discordant/missing data. The results of a selective literature research, including "omalizumab, controlled studies, randomized trial, real-life studies" as key words are discussed. Though some similarities between RCTs and R-L studies strengthen omalizumab efficacy and safety outcomes, significant differences concerning study population features, follow-up duration, local adverse events and drop-out rate for treatment inefficacy emerge between the two study categories. Furthermore the comparative analysis between RCTs and R-L studies highlights the need for further research, concerning in particular long-term effects of omalizumab and its impact on asthma comorbidities. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Metabolic and Endocrine Response and Health Implications of Consuming Sugar-Sweetened Beverages: Findings From Recent Randomized Controlled Trials123

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Rippe, James M.

2013-01-01

Fructose-containing sugars, including fructose itself, high fructose corn syrup (HFCS), and sucrose have engendered considerable controversy. The effects of HFCS and sucrose in sugar-sweetened beverages, in particular, have generated intense scientific debate that has spilled over to the public. This controversy is related to well-known differences in metabolism between fructose and glucose in the liver. In addition, research studies have often been conducted comparing pure fructose and pure glucose even though neither is consumed to any appreciable degree in isolation in the human diet. Other evidence has been drawn from animal studies and epidemiologic or cohort studies. Few randomized controlled trials (RCTs) have compared HFCS with sucrose (the 2 sugars most commonly consumed in the human diet) at dosage amounts within the normal human consumption range. This review compares results of recently concluded RCTs with other forms of evidence related to fructose, HFCS, and sucrose. We conclude that great caution must be used when suggesting adverse health effects of consuming these sugars in the normal way they are consumed and at the normal amounts in the human diet, because RCTs do not support adverse health consequences at these doses when employing these sugars. PMID:24228199

Regression Discontinuity and Randomized Controlled Trial Estimates: An Application to The Mycotic Ulcer Treatment Trials.

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Oldenburg, Catherine E; Venkatesh Prajna, N; Krishnan, Tiruvengada; Rajaraman, Revathi; Srinivasan, Muthiah; Ray, Kathryn J; O'Brien, Kieran S; Glymour, M Maria; Porco, Travis C; Acharya, Nisha R; Rose-Nussbaumer, Jennifer; Lietman, Thomas M

2018-08-01

We compare results from regression discontinuity (RD) analysis to primary results of a randomized controlled trial (RCT) utilizing data from two contemporaneous RCTs for treatment of fungal corneal ulcers. Patients were enrolled in the Mycotic Ulcer Treatment Trials I and II (MUTT I & MUTT II) based on baseline visual acuity: patients with acuity ≤ 20/400 (logMAR 1.3) enrolled in MUTT I, and >20/400 in MUTT II. MUTT I investigated the effect of topical natamycin versus voriconazole on best spectacle-corrected visual acuity. MUTT II investigated the effect of topical voriconazole plus placebo versus topical voriconazole plus oral voriconazole. We compared the RD estimate (natamycin arm of MUTT I [N = 162] versus placebo arm of MUTT II [N = 54]) to the RCT estimate from MUTT I (topical natamycin [N = 162] versus topical voriconazole [N = 161]). In the RD, patients receiving natamycin had mean improvement of 4-lines of visual acuity at 3 months (logMAR -0.39, 95% CI: -0.61, -0.17) compared to topical voriconazole plus placebo, and 2-lines in the RCT (logMAR -0.18, 95% CI: -0.30, -0.05) compared to topical voriconazole. The RD and RCT estimates were similar, although the RD design overestimated effects compared to the RCT.

Benchmarking Controlled Trial--a novel concept covering all observational effectiveness studies.

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Malmivaara, Antti

2015-06-01

The Benchmarking Controlled Trial (BCT) is a novel concept which covers all observational studies aiming to assess effectiveness. BCTs provide evidence of the comparative effectiveness between health service providers, and of effectiveness due to particular features of the health and social care systems. BCTs complement randomized controlled trials (RCTs) as the sources of evidence on effectiveness. This paper presents a definition of the BCT; compares the position of BCTs in assessing effectiveness with that of RCTs; presents a checklist for assessing methodological validity of a BCT; and pilot-tests the checklist with BCTs published recently in the leading medical journals.

A systematic review of randomized controlled trials of bupropion versus methylphenidate in the treatment of attention-deficit/hyperactivity disorder

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Maneeton N

2014-08-01

Full Text Available Narong Maneeton,1 Benchalak Maneeton,1 Suthi Intaprasert,1 Pakapan Woottiluk2 1Department of Psychiatry, Faculty of Medicine, 2Psychiatric Nursing Division, Faculty of Nursing, Chiang Mai University, Chiang Mai, ThailandBackground: Some trials have suggested that bupropion, as well as methylphenidate, is bene­ficial in the treatment of attention-deficit/hyperactivity disorder (ADHD.Objectives: The purpose of this systematic review was to summarize the efficacy, acceptability, and tolerability of bupropion in comparison with methylphenidate for ADHD treatment. Included studies were randomized controlled trials (RCTs that compared bupropion and methylphenidate. Clinical studies conducted between January 1991 and January 2014 were reviewed.Data sources: MEDLINE®, EMBASE™, CINAHL, PsycINFO®, and the Cochrane Controlled Trials Register were searched in January 2014. Additionally, clinical trials were identified from the databases of ClinicalTrials.gov and the EU Clinical Trials Register.Study eligible criteria, participants, and interventions: All RCTs of bupropion and methylphenidate reporting final outcomes relevant to 1 ADHD severity, 2 response or remission rates, 3 overall discontinuation rate, or 4 discontinuation rate due to adverse events. Language restriction was not applied.Study appraisal and synthesis methods: The relevant clinical trials were examined and the data of interest were extracted. Additionally, the risks of bias were also inspected. The efficacy outcomes were the mean changed scores of ADHD rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate and the discontinuation rate due to adverse events were determined. Relative risks and weighted mean differences or standardized mean differences with 95% confidence intervals were estimated using a random effect model.Results: A total of 146 subjects in four RCTs comparing bupropion with methylphenidate in the treatment of

Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials

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Maneeton Narong

2012-09-01

Full Text Available Abstract Background Schizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect. Objectives This meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD. Only the randomized controlled trials (RCTs comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012. Data sources MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression. Study eligible criteria, participants and interventions Eligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i depression severity, ii response rate, iii overall discontinuation rate, or iv discontinuation rate due to adverse events. No language restriction was applied. Study appraisal and synthesis methods All abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs and weighted mean differences (WMDs with 95% confidence intervals (CIs were computed by using a random effect model. Results A total of 1,497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR. The pooled mean change scores of the Montgomery-Asberg Depression

Improving transparency and reproducibility through registration: The status of intervention trials published in clinical psychology journals.

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Cybulski, Lukasz; Mayo-Wilson, Evan; Grant, Sean

2016-09-01

Prospective registration increases the validity of randomized controlled trials (RCTs). In the United States, registration is a legal requirement for drugs and devices regulated by the Food and Drug Administration (FDA), and many biomedical journals refuse to publish trials that are not registered. Trials in clinical psychology have not been subject to these requirements; it is unknown to what extent they are registered. We searched the 25 highest-impact clinical psychology journals that published at least 1 RCT of a health-related psychological intervention in 2013. For included trials, we evaluated their registration status (prospective, retrospective, not registered) and the completeness of their outcome definitions. We identified 163 articles that reported 165 RCTs; 73 (44%) RCTs were registered, of which only 25 (15%) were registered prospectively. Of registered RCTs, only 42 (58%) indicated their registration status in the publication. Only 2 (1% of all trials) were registered prospectively and defined their primary outcomes completely. For the primary outcome(s), 72 (99%) of all registrations defined the domain, 67 (92%) the time frame, and 48 (66%) the specific measurements. Only 19 (26%) and 5 (7%) defined the specific metric and method of aggregation, respectively, for all primary outcomes. Very few reports of RCTs published in clinical psychology journals were registered prospectively and completely. Clinical psychology journals could improve transparency and reproducibility, as well as reduce bias, by requiring complete prospective trial registration for publication and by including trial registration numbers in all reports of RCTs. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Sample Size Calculation: Inaccurate A Priori Assumptions for Nuisance Parameters Can Greatly Affect the Power of a Randomized Controlled Trial.

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Elsa Tavernier

Full Text Available We aimed to examine the extent to which inaccurate assumptions for nuisance parameters used to calculate sample size can affect the power of a randomized controlled trial (RCT. In a simulation study, we separately considered an RCT with continuous, dichotomous or time-to-event outcomes, with associated nuisance parameters of standard deviation, success rate in the control group and survival rate in the control group at some time point, respectively. For each type of outcome, we calculated a required sample size N for a hypothesized treatment effect, an assumed nuisance parameter and a nominal power of 80%. We then assumed a nuisance parameter associated with a relative error at the design stage. For each type of outcome, we randomly drew 10,000 relative errors of the associated nuisance parameter (from empirical distributions derived from a previously published review. Then, retro-fitting the sample size formula, we derived, for the pre-calculated sample size N, the real power of the RCT, taking into account the relative error for the nuisance parameter. In total, 23%, 0% and 18% of RCTs with continuous, binary and time-to-event outcomes, respectively, were underpowered (i.e., the real power was 90%. Even with proper calculation of sample size, a substantial number of trials are underpowered or overpowered because of imprecise knowledge of nuisance parameters. Such findings raise questions about how sample size for RCTs should be determined.

Effect of Replacing Animal Protein with Plant Protein on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

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Viguiliouk, Effie; Stewart, Sarah E; Jayalath, Viranda H; Ng, Alena Praneet; Mirrahimi, Arash; de Souza, Russell J; Hanley, Anthony J; Bazinet, Richard P; Blanco Mejia, Sonia; Leiter, Lawrence A; Josse, Robert G; Kendall, Cyril W C; Jenkins, David J A; Sievenpiper, John L

2015-12-01

Previous research on the effect of replacing sources of animal protein with plant protein on glycemic control has been inconsistent. We therefore conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of this replacement on glycemic control in individuals with diabetes. We searched MEDLINE, EMBASE, and Cochrane databases through 26 August 2015. We included RCTs ≥ 3-weeks comparing the effect of replacing animal with plant protein on HbA1c, fasting glucose (FG), and fasting insulin (FI). Two independent reviewers extracted relevant data, assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q-statistic) and quantified (I²-statistic). Thirteen RCTs (n = 280) met the eligibility criteria. Diets emphasizing a replacement of animal with plant protein at a median level of ~35% of total protein per day significantly lowered HbA1c (MD = -0.15%; 95%-CI: -0.26, -0.05%), FG (MD = -0.53 mmol/L; 95%-CI: -0.92, -0.13 mmol/L) and FI (MD = -10.09 pmol/L; 95%-CI: -17.31, -2.86 pmol/L) compared with control arms. Overall, the results indicate that replacing sources of animal with plant protein leads to modest improvements in glycemic control in individuals with diabetes. Owing to uncertainties in our analyses there is a need for larger, longer, higher quality trials. ClinicalTrials.gov registration number: NCT02037321.

Heterogeneity of wound outcome measures in RCTs of treatments for VLUs: a systematic review.

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Gethin, G; Killeen, F; Devane, D

2015-05-01

Venous leg ulcers (VLUs) affect up to 4% of the population aged over 65 years. Outcomes of randomised controlled trials (RCTs) in VLUs are important to guide clinical and resource decision making. Our objective was to identify what endpoints and wound bed outcomes were assessed in RCTs in VLUs; how these were assessed and what reference was made to validity and reliability of methods used. A systematic review of all full text RCTs, published in English, from 1998-2013. Our criteria were met by 102 studies. There were 78 different endpoints recorded, the majority (n=34) related to healing and were evaluated at 12 different times points. Size was the most frequently reported outcome measure (n=99), with photographs, tissue type, exudate, odour and pain also recorded. There was poor reporting of methods used to assess outcomes. Visual analogue scales predominated as a method of assessment, but 95% of studies made no reference to the validity or reliability of assessment methods. Future research in VLUs requires standards for measuring outcomes with acceptable inter-rater reliability and validated measures of patient-reported outcomes.

Comparison between herbal medicine and fluoxetine for depression: a systematic review of randomized controlled trials.

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Ren, Yi; Zhu, Chenjun; Wu, Jianjun; Zheng, Ruwen; Cao, Huijaun

2015-10-01

To evaluate the effectiveness and safety of Chinese herbal medicine (CHM) versus fluoxetine on depression. A systematic review of randomized controlled trials (RCTs). RCT with two parallel groups that compared CHM and fluoxetine on treatment of depression with reported decreased Hamilton Depression Scale (HAMD) and adverse events during treatment were included after searching through six electric-databases. The methodological quality of RCTs was assessed according to the Cochrane risk of bias tool. Meta-analysis was conducted using RevMan 5.3 software with pooled mean difference (MD) or risk ratio (RR) and their 95% confidence interval (CI) if no significant heterogeneity was detected. A SOF table was generated using GRADEPro software to evaluate the overall quality of the evidence. Twenty-six trials with 3294 participants were included in the review. Most of them had high risk of bias during conducting and reporting. The results achieved weak evidence which showed CHM had similar effect to fluoxetine (20mg/day) on relieving depression according to HAMD assessment (for primary depression: MD=-0.08, 95%CI -0.98-0.82; for secondary depression: MD=-0.36, 95%CI -1.55-0.83), but fewer incidences of adverse events than the drug (for primary depression: RR=0.31, 95%CI 0.17-0.59; for post-stroke depression: RR=0.04, 95%CI 0.00-0.25). No serious adverse event was found in neither CHM nor fluoxetine group. Due to the poor quality of included trials and the potential publication bias of this review, no confirmed conclusion could be draw to evaluate the effectiveness and safety of CHM for depression compared with fluoxetine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Laparoscopic versus open repair for perforated peptic ulcer: A meta analysis of randomized controlled trials.

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Tan, Shanjun; Wu, Guohao; Zhuang, Qiulin; Xi, Qiulei; Meng, Qingyang; Jiang, Yi; Han, Yusong; Yu, Chao; Yu, Zhen; Li, Ning

2016-09-01

The role of laparoscopic surgery in the repair for peptic ulcer disease is unclear. The present study aimed to compare the safety and efficacy of laparoscopic versus open repair for peptic ulcer disease. Randomized controlled trials (RCTs) comparing laparoscopic versus open repair for peptic ulcer disease were identified from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and references of identified articles and relevant reviews. Primary outcomes were postoperative complications, mortality, and reoperation. Secondary outcomes were operative time, postoperative pain, postoperative hospital stay, nasogastric tube duration, and time to resume diet. Statistical analysis was carried out by Review Manage software. Five RCTs investigating a total of 549 patients, of whom, 279 received laparoscopic repair and 270 received open repair, were included in the final analysis. There were no significant differences between these two procedures in some primary outcomes including overal postoperative complication rate, mortality, and reoperation rate. Subcategory analysis of postoperative complications showed that laparoscopic repair had also similar rates of repair site leakage, intra-abdominal abscess, postoperative ileus, pneumonia, and urinary tract infection as open surgery, except of the lower surgical site infection rate (P peptic ulcer. The obvious advantages of laparoscopic surgery are the lower surgical site infection rate, shorter nasogastric tube duration and less postoperative pain. However, more higher quality studies should be undertaken to further assess the safety and efficacy of laparoscopic repair for peptic ulcer disease. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Analysis of the Quality of Clinical Trials Published in Spanish-Language Dermatology Journals Between 1997 and 2012.

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Sanclemente, G; Pardo, H; Sánchez, S; Bonfill, X

2016-01-01

The value of randomized clinical trials (RCTs) undertaken to identify an association between an intervention and an outcome is determined by their quality and scientific rigor. To assess the methodological quality of RCTs published in Spanish-language dermatology journals. By way of a systematic manual search, we identified all the RCTs in journals published in Spain and Latin America between 1997 (the year in which the CONSORT statement was published) and 2012. Risk of bias was evaluated for each RCT by assessing the following domains: randomization sequence generation, allocation concealment, blinding of patients and those assessing outcomes, missing data, and patient follow-up. Source of funding and conflict of interest statements, if any, were recorded for each study. The search identified 70 RCTs published in 21 journals. Most of the RCTs had a high risk of bias, primarily because of gaps in the reporting of important methodological aspects. The source of funding was reported in only 15 studies. In spite of the considerable number of Spanish and Latin American journals, few RCTs have been published in the 15 years analyzed. Most of the RCTs published had serious defects in that the authors omitted methodological information essential to any evaluation of the quality of the trial and failed to report sources of funding or possible conflicts of interest for the authors involved. Authors of experimental clinical research in dermatology published in Spain and Latin America need to substantially improve both the design of their trials and the reporting of results. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Randomised controlled trials in Scandinavian educational research

DEFF Research Database (Denmark)

Pontoppidan, Maiken; Keilow, Maria; Dietrichson, Jens

2018-01-01

of this paper is to examine the history of randomised controlled trials in Scandinavian compulsory schools (grades 0–10; pupil ages 6-15). Specifically, we investigate drivers and barriers for randomised controlled trials in educational research and the differences between the three Scandinavian countries...... crucial for the implementation of RCTs and are likely more important in smaller countries such as the Scandinavian ones. Supporting institutions have now been established in all three countries, and we believe that the use of RCTs in Scandinavian educational research is likely to continue....... or more interventions were randomly assigned to groups of students and carried out in a school setting with the primary aim of improving the academic performance of children aged 6-15 in grades 0–10 in Denmark, Norway, or Sweden. We included both conducted and ongoing trials. Publications that seemed...

Baseline participant characteristics and risk for dropout from ten obesity randomized controlled trials: a pooled analysis of individual level data.

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Kaiser, Kathryn A; Affuso, Olivia; Desmond, Renee; Allison, David B

Understanding participant demographic characteristics that inform the optimal design of obesity RCTs have been examined in few studies. The objective of this study was to investigate the association of individual participant characteristics and dropout rates (DORs) in obesity randomized controlled trials (RCT) by pooling data from several publicly available datasets for analyses. We comprehensively characterize DORs and patterns in obesity RCTs at the individual study level, and describe how such rates and patterns vary as a function of individual-level characteristics. We obtained and analyzed nine publicly-available, obesity RCT datasets that examined weight loss or weight gain prevention as a primary or secondary endpoint. Four risk factors for dropout were examined by Cox proportional hazards including sex, age, baseline BMI, and race/ethnicity. The individual study data were pooled in the final analyses with a random effect for study, and HR and 95% CIs were computed. Results of the multivariate analysis indicated that the risk of dropout was significantly higher for females compared to males (HR= 1.24, 95% CI = 1.05, 1.46). Hispanics and Non-Hispanic blacks had a significantly higher dropout rate compared to non-Hispanic whites (HR= 1.62, 95% CI = 1.37, 1.91; HR= 1.22, 95% CI = 1.11, 1.35, respectively). There was a significantly increased risk of dropout associated with advancing age (HR= 1.02, 95% CI = 1.01, 1.02) and increasing BMI (HR= 1.03, 95% CI = 1.03, 1.04). As more studies may focus on special populations, researchers designing obesity RCTs may wish to oversample in certain demographic groups if attempting to match comparison groups based on generalized estimates of expected dropout rates, or otherwise adjust a priori power estimates. Understanding true reasons for dropout may require additional methods of data gathering not generally employed in obesity RCTs, e.g. time on treatment.

A core outcome set for clinical trials on non-specific low back pain: study protocol for the development of a core domain set

DEFF Research Database (Denmark)

Chiarotto, Alessandro; Terwee, Caroline B; Deyo, Richard A.

2014-01-01

on randomized controlled trials (RCTs) included in a Cochrane systematic review on the effectiveness of constraint-induced movement therapy (CIMT) for stroke patients. METHODS: We extracted data on the functional independence measure (FIM) and the action research arm test (ARAT) from RCTs that compared CIMT...

Angioplasty Guided by Intravascular Ultrasound: Meta-Analysis of Randomized Clinical Trials

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Figueiredo, José Albuquerque Neto de, E-mail: jafneto@cardiol.br; Nogueira, Iara Antonia Lustosa [Universidade Federal do Maranhão, São Luiz, MA (Brazil); Figueiro, Mabel Fernandes; Buehler, Anna Maria; Berwanger, Otavio [Instituto de Ensino e Pesquisa do Hospital do Coração, São Paulo, SP (Brazil)

2013-08-15

The impact of intravascular ultrasound (IVUS) use on stenting has shown inconclusive results. Systematic review and meta-analysis of the impact of IVUS on stenting regarding the clinical and angiographic evolution. A search was performed in Medline/Pubmed, CENTRAL, Embase, Lilacs, Scopus and Web of Science databases. It included randomized clinical trials (RCTs) that evaluated the implantation of stents guided by IVUS, compared with those using angiography alone (ANGIO). The minimum follow-up duration was six months and the following outcomes were assessed: thrombosis, mortality, myocardial infarction, percutaneous and surgical revascularization, major adverse cardiovascular events (MACE) and restenosis. The binary outcomes were presented considering the number of events in each group; the estimates were generated by a random effects model, considering Mantel-Haenszel statistics as weighting agent and magnitude of effect for the relative risk (RR) with its respective 95% confidence interval (95%CI). Higgins I{sup 2} test was used to quantify the consistency between the results of each study. A total of 2,689 articles were evaluated, including 8 RCTs. There was a 27% reduction in angiographic restenosis (RR: 0.73, 95% CI: 0.54-0.97, I{sup 2} = 51%) and statistically significant reduction in the rates of percutaneous revascularization and overall (RR: 0.88; 95% CI: 0.51 to 1.53, I{sup 2} = 61%, RR: 0.73, 95% CI: 0.54 to 0.99, I{sup 2} = 55%), with no statistical difference in surgical revascularization (RR: 0.95, 95% CI: 0.52-1.74, I{sup 2} = 0%) in favor of IVUS vs. ANGIO. There were no differences regarding the other outcomes in the comparison between the two strategies. Angioplasty with stenting guided by IVUS decreases the rates of restenosis and revascularization, with no impact on MACE, acute myocardial infarction, mortality or thrombosis outcomes.

Effect of Aerobic Training on Peak Oxygen Uptake Among Seniors Aged 70 or Older: A Meta-Analysis of Randomized Controlled Trials.

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Bouaziz, Walid; Kanagaratnam, Lukshe; Vogel, Thomas; Schmitt, Elise; Dramé, Moustapha; Kaltenbach, Georges; Geny, Bernard; Lang, Pierre Olivier

2018-01-02

Older adults undergo a progressive decline in cardiorespiratory fitness and functional capacity. This lower peak oxygen uptake (VO 2peak ) level is associated with increased risk of frailty, dependency, loss of autonomy, and mortality from all causes. Regular physical activity and particularly aerobic training (AT) have been shown to contribute to better and healthy aging. We conducted a meta-analysis to measure the exact benefit of AT on VO 2peak in seniors aged 70 years or older. A comprehensive, systematic database search for articles was performed in Embase, Medline, PubMed Central, Science Direct, Scopus, and Web of Science using key words. Two reviewers independently assessed interventional studies for potential inclusion. Ten randomized controlled trials (RCTs) were included totaling 348 seniors aged 70 years or older. Across the trials, no high risk of bias was measured and all considered open-label arms for controls. With significant heterogeneity between the RCTs (all p seniors were, respectively, 1.72 (95% CI: 0.34-3.10) and 1.47 (95% CI: 0.60-2.34). This meta-analysis confirms the AT-associated benefits on VO 2peak in healthy and unhealthy seniors.

Is escitalopram really relevantly superior to citalopram in treatment of major depressive disorder? A meta-analysis of head-to-head randomized trials.

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Trkulja, Vladimir

2010-02-01

To evaluate clinical relevance of differences between escitalopram and citalopram (equimolar) for major depressive disorder. Review and meta-analysis of comparative randomized controlled trials (RCT). Comparisons were in relation to Montgomery-Asberg depression rating scale (MADRS) score reduction at weeks 1 (5 RCTs), 4 (5 RCTs), 6 (4 RCTs), 8 (5 RCTs), and 24 (1 RCT); proportion of responders at weeks 2, 4, 6 (2 RCTs for each time point), 8 (5 RCTs), and 24 (1 RCT); clinical global impression-severity (CGI-S) reduction at weeks 6 (1 RCT), 8 (5 RCTs), and 24 (1 RCT), and discontinuation due to adverse events or inefficacy during short-term (up to 8 weeks) and medium-term (24 weeks) treatment. MADRS reduction was greater with escitalopram, but 95% confidence intervals (CI) around the mean difference were entirely or largely below 2 scale points (minimally important difference) and CI around the effect size (ES) was below 0.32 ("small") at all time points. Risk of response was higher with escitalopram at week 8 (relative risk, 1.14; 95% CI, 1.04 to 1.26) but number needed to treat was 14 (95% CI, 7 to 111). All 95% CIs around the mean difference and ES of CGI-S reduction at week 8 were below 0.32 points and the limit of "small," respectively. Data for severe patients (MADRS> or =30) are scarce (only 1 RCT), indicating somewhat greater efficacy (response rate and MADRS reduction at week 8, but not CGI-S reduction) of escitalopram, but without compelling evidence of clinically relevant differences. Discontinuations due to adverse events or inefficacy up to 8 weeks of treatment were comparable. Data for the period up to 24 weeks are scarce and inconclusive. Presently, the claims about clinically relevant superiority of escitalopram over citalopram in short-to-medium term treatment of major depressive disorder are not supported by evidence.

Patient Characteristics Associated With a Successful Response to Nurse-Led Care Programs Targeting the Oldest-Old: A Comparison of Two RCTs.

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Bleijenberg, Nienke; Imhof, Lorenz; Mahrer-Imhof, Romy; Wallhagen, Margaret I; de Wit, Niek J; Schuurmans, Marieke J

2017-06-01

To improve the effectiveness of community-based care programs, especially those targeting the oldest-old population (80+), data are needed that elucidate those factors associated with a successful response to the intervention. Two comparable nurse-led care programs have been evaluated in two large randomized controlled trials (RCTs), one in Switzerland and one in the Netherlands. To identify common patient characteristics that are related to a successful response to proactive nurse-led care, we explored if and to what extent, identical factors were present in both study populations. A secondary data analysis using trial data from the intervention group of both RCTs was conducted. The study sample consisted 461 older adults, 230 from the U-PROFIT trial (the Netherlands) and 231 from the HPC trial (Switzerland). The mean age of the total sample was 85.1 years (SD 3.7). The UPROFIT intervention, delivered by registered nurses, included a frailty assessment and a comprehensive geriatric assessment (CGA) at home followed by an individualized evidence-based care plan, care coordination, and follow-up. The HCP intervention was delivered by advanced practice nurses consisting of four home visits and three phone calls, and was guided by the principles of health promotion, empowerment, partnership, and family-centeredness. A successful response was defined as "stable" or "no decline" in daily functioning at follow-up. Daily functioning was measured with 13 items of activities of daily living and instrumental activities of daily living. Multivariate logistic regression models were applied to calculate the association between individual characteristics and a successful response. Almost half of the participants in the U-PROFIT trial (50.9%), and two-thirds (65.7%) of the participants in the HCP trial had a successful response at follow-up. Fewer comorbidities and a better self-rated health had the strongest predictive value for benefiting from the intervention (OR = 0.83 [95

Hypnotherapy for insomnia: a systematic review and meta-analysis of randomized controlled trials.

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Lam, Tak-Ho; Chung, Ka-Fai; Yeung, Wing-Fai; Yu, Branda Yee-Man; Yung, Kam-Ping; Ng, Tommy Ho-Yee

2015-10-01

To examine the efficacy and safety of hypnotherapy for insomnia as compared to placebo, pharmacological or non-pharmacological intervention, or no treatment. A systematic search on major electronic databases was conducted up until March 2014. Inclusion criteria are: (1) randomized controlled trials (RCTs) or quasi-RCTs; (2) intervention targeted at improving sleep; (3) hypnosis as an intervention; and (4) English language articles. Sleep diary variable is the primary outcome measure. Six RCTs of hypnotherapy and seven on autogenic training or guided imagery, comprising 502 subjects, were included. Eleven of the 13 studies had low methodological quality, as indicated by a modified Jadad score below 3, and high risks of bias in blinding and design of the control interventions. No adverse events related to hypnosis were reported, though seldom investigated. Meta-analyses found hypnotherapy significantly shortened sleep latency compared to waitlist (standardized mean difference, SMD=-0.88, 95% confidence interval (CI): -1.56, -0.19, P=0.01, I(2)=15%), but no difference compared to sham intervention (SMD: -1.08, 95% CI: -3.15, 0.09, P=0.31, I(2)=90%). Similar results were found for autogenic training or guided imagery (SMD with waitlist=-1.16, 95% CI: -1.92, -0.40, P=0.003, I(2)=0%; SMD with sham intervention=-0.50, 95% CI: -1.19, 0.19, P=0.15, I(2)=0%). Generalizability of the positive results is doubtful due to the relatively small sample size and methodological limitations. Future studies with larger sample size and better study design and methodology are called for. Copyright © 2015 Elsevier Ltd. All rights reserved.

Total glucosides of paeony for rheumatoid arthritis: A systematic review of randomized controlled trials.

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Luo, Jing; Jin, Di-Er; Yang, Guo-Yan; Zhang, Ying-Ze; Wang, Jian-Ming; Kong, Wei-Ping; Tao, Qing-Wen

2017-10-01

Total glucosides of paeony (TGP) is commonly used to treat rheumatoid arthritis (RA) in China. However, clinical practice hasn't been well informed by evidence from appropriately conducted systematic reviews. This PRISMA-compliant systematic review aims at examining the effectiveness and safety of TGP for RA. Randomized controlled trials (RCTs) comparing TGP with placebo, no treatment, or disease-modifying antirheumatic drugs (DMARDs) for patients with RA were retrieved by searching seven databases. Primary outcomes included disease improvement and disease remission. Secondary outcomes included adverse effects, pain, health-related quality of life, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Data extraction and analyses were conducted according to the Cochrane standards. We assessed risk of bias for each included studies and quality of evidence on pre-specified outcomes. Eight studies enrolling 1209 patients with active RA were included in this systematic review. On the basis of traditional DMARD(s), TGP might be beneficial for patients with RA in improvement of American College of Rheumatology (ACR) 20 response rate, ACR 50 response rate, ACR70 response rate, and in reduction of adverse effects, compared with no treatment. The overall methodological quality of included studies and the quality of evidence for each outcome were limited. Current trials suggested potential benefits of TGP for RA on the basis of traditional DMARD(s). Therefore, TGP may be a good choice for RA as an adjuvant therapy. However, considering the limited methodological quality and strength of evidence, high-quality RCTs are warranted to support the use of TGP for RA. Copyright © 2017. Published by Elsevier Ltd.

Ranking of patient and surgeons' perspectives for endpoints in randomized controlled trials--lessons learned from the POVATI trial [ISRCTN 60734227].

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Fischer, Lars; Deckert, Andreas; Diener, Markus K; Zimmermann, Johannes B; Büchler, Markus W; Seiler, Christoph M

2011-10-01

Surgical trials focus mainly on mortality and morbidity rates, which may be not the most important endpoints from the patient's perspective. Evaluation of expectations and needs of patients enrolled in clinical trials can be analyzed using a procedure called ranking. Within the Postsurgical Pain Outcome of Vertical and Transverse Abdominal Incision randomized trial (POVATI), the perspectives of participating patients and surgeons were assessed as well as the influence of the surgical intervention on patients' needs. All included patients of the POVATI trial were asked preoperatively and postoperatively to rank predetermined outcome variables concerning the upcoming surgical procedure (e.g., pain, complication, cosmetic result) hierarchically according to their importance. Preoperatively, the surgeons were asked to do the same. One hundred eighty two out of 200 randomized patients (71 females, 111 males; mean age 59 years) returned the ranking questionnaire preoperatively and 152 patients (67 females, 85 males; mean age 60 years) on the day of discharge. There were no differences between the two groups with respect to the distribution of ranking variables (p > 0.05). Thirty-five surgeons (7 residents, 6 fellows, and 22 consultants) completed the same ranking questionnaire. The order of the four most important ranking variables for both patients and surgeons were death, avoiding of postoperative complications, avoiding of intraoperative complications, and pain. Surgeons ranked the variable "cosmetic result" significantly as more important compared to patients (p = 0.034, Fisher's exact test). Patients and surgeons did not differ in ranking predetermined outcomes in the POVATI trial. Only the variable "cosmetic result" is significantly more important from the surgeon's than from the patient's perspective. Ranking of outcomes might be a beneficial tool and can be a proper addition to RCTs.

Geographic differences in heart failure trials.

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Ferreira, João Pedro; Girerd, Nicolas; Rossignol, Patrick; Zannad, Faiez

2015-09-01

Randomized controlled trials (RCTs) are essential to develop advances in heart failure (HF). The need for increasing numbers of patients (without substantial cost increase) and generalization of results led to the disappearance of international boundaries in large RCTs. The significant geographic differences in patients' characteristics, outcomes, and, most importantly, treatment effect observed in HF trials have recently been highlighted. Whether the observed regional discrepancies in HF trials are due to trial-specific issues, patient heterogeneity, structural differences in countries, or a complex interaction between factors are the questions we propose to debate in this review. To do so, we will analyse and review data from HF trials conducted in different world regions, from heart failure with preserved ejection fraction (HF-PEF), heart failure with reduced ejection fraction (HF-REF), and acute heart failure (AHF). Finally, we will suggest objective and actionable measures in order to mitigate regional discrepancies in future trials, particularly in HF-PEF where prognostic modifying treatments are urgently needed and in which trials are more prone to selection bias, due to a larger patient heterogeneity. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Effect of Probiotics on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Meta-Analysis of 12 Randomized Controlled Trials.

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Yao, Kecheng; Zeng, Linghai; He, Qian; Wang, Wei; Lei, Jiao; Zou, Xiulan

2017-06-22

BACKGROUND It has been unclear whether supplemental probiotics therapy improves clinical outcomes in type 2 diabetic patients. This meta-analysis aimed to summarize the effect of probiotics on glucose and lipid metabolism and C-reactive protein (CRP) from 12 randomized controlled trials (RCTs). MATERIAL AND METHODS An up-to-date search was performed for all relevant RCTs up to April 2016 from PubMed, Embase, and Cochrane Library. Standardized mean difference (SMD) and weighted mean difference (WMD) were calculated for a fixed-effect and random-effect meta-analysis to assess the impact of supplemental probiotics on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, and CRP level. RESULTS A total of 12 studies (684 patients) were entered into the final analysis. The effect of probiotics was significant on reducing HbA1c level (standardized mean difference [SMD], -0.38; confidence interval [CI], -0.62 to -0.14, P=0.002; I²=0%, P=0.72 for heterogeneity), fasting insulin level (SMD, -0.38; CI -0.59 to -0.18, P=0.0003; I²=0%, P=0.81 for heterogeneity), and HOMA-IR (SMD, -0.99; CI -1.52 to -0.47, P=0.0002; I²=86%, Pprobiotics on FPG, CRP, or lipid profile were either non-significant or highly heterogeneous. CONCLUSIONS This meta-analysis demonstrated that probiotics supplementation was associated with significant improvement in HbA1c and fasting insulin in type 2 diabetes patients. More randomized placebo-controlled trials with large sample sizes are warranted to confirm our conclusions.

The effects of epidural/spinal opioids in labour analgesia on neonatal outcomes: a meta-analysis of randomized controlled trials.

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Wang, Kai; Cao, Liang; Deng, Qian; Sun, Li-Qiang; Gu, Tian-Yu; Song, Jie; Qi, Dun-Yi

2014-08-01

Epidural/spinal opioids are increasingly used to relieve parturients' pain in labour. Some studies indicate that opioids can induce side effects in neonates, such as respiratory depression and neurobehavioural changes. This meta-analysis aimed to clarify the effects of opioids in labour analgesia on neonates. PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE™ were searched for relevant randomized controlled trials (RCTs). The neonatal data of Apgar scores, Neurological and Adaptive Capacity Scores (NACS), and umbilical cord pH values were extracted. Statistical analyses were carried out using Review Manager 5.2 and Stata(®) 10. Twenty-one trials with 2,859 participants were included in our meta-analysis. No difference in the incidence of Apgar scores analgesia are safe for neonates up to 24 hr after delivery. In future studies, more attention should be paid to the long-term side effects in neonates.

Systematic literature review of clinical trials evaluating pharmacotherapy for overactive bladder in elderly patients: An assessment of trial quality.

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Kistler, Kristin D; Xu, Yingxin; Zou, Kelly H; Ntanios, Fady; Chapman, Douglass S; Luo, Xuemei

2018-01-01

Overactive bladder (OAB) disproportionately affects older-aged adults, yet most randomized controlled trials (RCTs) underrepresent patients ≥65. This systematic literature review (SLR) identified RCTs evaluating β-3 adrenergic agonists or muscarinic antagonists in elderly patients with OAB, and compared study quality across trials. MEDLINE ® , Embase ® , and Cochrane Collaboration Central Register of Clinical Trials databases were searched from inception through April 28, 2015 to identify published, peer-reviewed RCT reports evaluating β-3 adrenergic agonists or muscarinic antagonists in elderly OAB patients (either ≥65 years or study-described as "elderly"). To assess study quality of RCT reports, we focused on internal/external validity, assessed via two scales: the validated Effective Public Health Practice Project [EPHPP]): Quality Assessment Tool for Quantitative Studies, and a tool commissioned by the Agency for Healthcare Research and Quality (AHRQ). Database searches yielded 1380 records that were then screened according to predefined inclusion/exclusion criteria. We included eight papers meeting study criteria. Despite scientific community efforts to improve RCT reporting standards, published reports still include incomplete and inconsistent reporting-of subject attrition, baseline patient characteristics, inclusion/exclusion criteria, and other important details. Only three of the eight OAB RCTs in this review received quality ratings of Strong (EPHPP) or Fair (AHRQ) and were multicenter with large samples. Despite the prevalence of OAB among older age individuals, relatively few RCTs evaluate OAB treatments explicitly among elderly subjects. The findings from this quality assessment suggest some areas for improvement in both conduct and reporting of future RCTs assessing OAB treatment in elderly. © 2017 Wiley Periodicals, Inc.

Exploring reasons for the observed inconsistent trial reports on intra-articular injections with hyaluronic acid in the treatment of osteoarthritis: Meta-regression analyses of randomized trials.

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Johansen, Mette; Bahrt, Henriette; Altman, Roy D; Bartels, Else M; Juhl, Carsten B; Bliddal, Henning; Lund, Hans; Christensen, Robin

2016-08-01

The aim was to identify factors explaining inconsistent observations concerning the efficacy of intra-articular hyaluronic acid compared to intra-articular sham/control, or non-intervention control, in patients with symptomatic osteoarthritis, based on randomized clinical trials (RCTs). A systematic review and meta-regression analyses of available randomized trials were conducted. The outcome, pain, was assessed according to a pre-specified hierarchy of potentially available outcomes. Hedges׳s standardized mean difference [SMD (95% CI)] served as effect size. REstricted Maximum Likelihood (REML) mixed-effects models were used to combine study results, and heterogeneity was calculated and interpreted as Tau-squared and I-squared, respectively. Overall, 99 studies (14,804 patients) met the inclusion criteria: Of these, only 71 studies (72%), including 85 comparisons (11,216 patients), had adequate data available for inclusion in the primary meta-analysis. Overall, compared with placebo, intra-articular hyaluronic acid reduced pain with an effect size of -0.39 [-0.47 to -0.31; P hyaluronic acid. Based on available trial data, intra-articular hyaluronic acid showed a better effect than intra-articular saline on pain reduction in osteoarthritis. Publication bias and the risk of selective outcome reporting suggest only small clinical effect compared to saline. Copyright © 2016 Elsevier Inc. All rights reserved.

Combined application of eicosapentaenoic acid and docosahexaenoic acid on depression in women: a meta-analysis of double-blind randomized controlled trials

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Yang JR

2015-08-01

Full Text Available Jia-run Yang, Dong Han, Zheng-xue Qiao, Xue Tian, Dong Qi, Xiao-hui QiuDepartment of Medical Psychology, Public Health Institute of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of ChinaObjectives: Previous randomized controlled trials (RCTs suggest that depression can be effectively treated by omega-3 polyunsaturated fatty acids (PUFAs. Therefore, we conducted this meta-analysis to systematically evaluate the clinical applicability of the combination of docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA, which are the two major bioactive types of PUFAs, in depressed women.Methods: RCTs that compared the combination of DHA and EPA to placebo for short-course treatment of depression in women were systematically reviewed up to March 2015. Outcome measurement was the standardized difference in means in clinical measure of depression severity. Random effect model was performed. Meta-regression analysis was performed to assess the effects of baseline depression scores.Results: Data were obtained from eight RCTs. In these RCTs, 182 patients received placebo and 185 patients received DHA and EPA. The pooled standardized difference in mean was 0.65 with 95% CI = [0.18, 1.12]. There was no relation between the efficacy and the baseline depression scores. The sensitivity analysis found that the combination of EPA and DHA as monotherapy yielded a standardized difference in means of 0.65 (95% CI =0.41, 0.90 without heterogeneity.Discussion: These results indicate a beneficial effect of the combination of EPA and DHA on depressed mood in women compared with placebo. The clinical applicability of EPA and DHA showed greater promise and should be further explored.Keywords: depression, omega-3 polyunsaturated fatty acids, PUFAs, docosahexaenoic acid, DHA, eicosapentaenoic acid, EPA

Recent Treatment Advances and New Trials in Adult Nephrotic Syndrome

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Eva Königshausen

2017-01-01

Full Text Available The etiology of nephrotic syndrome is complex and ranges from primary glomerulonephritis to secondary forms. Patients with nephrotic syndrome often need immunosuppressive treatment with its side effects and may progress to end stage renal disease. This review focuses on recent advances in the treatment of primary causes of nephrotic syndrome (idiopathic membranous nephropathy (iMN, minimal change disease (MCD, and focal segmental glomerulosclerosis (FSGS since the publication of the KDIGO guidelines in 2012. Current treatment recommendations are mostly based on randomized controlled trials (RCTs in children, small RCTs, or case series in adults. Recently, only a few new RCTs have been published, such as the Gemritux trial evaluating rituximab treatment versus supportive antiproteinuric and antihypertensive therapy in iMN. Many RCTs are ongoing for iMN, MCD, and FSGS that will provide further information on the effectiveness of different treatment options for the causative disease. In addition to reviewing recent clinical studies, we provide insight into potential new targets for the treatment of nephrotic syndrome from recent basic science publications.

Adherence to the CONSORT Statement in the Reporting of Randomized Controlled Trials on Pharmacological Interventions Published in Iranian Medical Journals

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Pooneh Sarveravan

2017-11-01

Full Text Available Background: Among manuscripts submitted to biomedical journals, randomized controlled trials (RCTs form the backbone of evidence-based medicine. Hence, their protocol should be designed rigorously and their results should be reported clearly. To improve the quality of RCT reporting, researchers developed the CONSORT Statement in 1996 and updated it in 2010. This study was designed to assess the quality of RCT reporting vis-à-vis adherence to CONSORT among articles published in Iranian medical journals (English, Persian, CONSORT-endorsing, and non-CONSORT-endorsing. Methods: In this cross-sectional study, all RCTs published in all Iranian medical journals from September 2012 to September 2013 were retrieved to evaluate their adherence to CONSORT. The journals’ instructions for authors were also reviewed to find out whether or not they endorsed CONSORT. The CONSORT 2010 Checklist was used. Microsoft Excel 2007 was applied to analyze the data, and MedCalc was employed to compare the groups. Results: Totally, 492 pharmacological RCTs that met our inclusion criteria were identified. Twenty-five items were reported in fewer than 50% of the articles. The differences between the articles published in Persian and English language journals were statistically significant in 17 items. The differences between the articles published in the CONSORT-endorsing and non-CONSORT-endorsing journals were significant in 8 items. Conclusion: Our findings showed very weak adherence to CONSORT. Authors, reviewers, and editors should be trained to use standards expressed by the CONSORT Group in reporting RCTs.

The efficacy and safety of medical leech therapy for osteoarthritis of the knee: A meta-analysis of randomized controlled trials.

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Wang, Haixia; Zhang, Jing; Chen, Liyan

2018-06-01

It is controversial on whether medical leech therapy is effective in improving pain and functional outcome in patients with knee osteoarthritis (OA). Therefore, we perform a meta-analysis from randomized controlled trials (RCTs) to evaluate the efficacy and safety of medical leech therapy in patients with knee OA. The PubMed, EMBASE, ScienceDirect, and Cochrane Library databases were systematically searched for literature up to January 2018. RCTs involving medical leech therapy in patients with knee OA were included. Two independent reviewers performed independent data abstraction. The I 2 statistic was used to assess heterogeneity. A fixed or random effects model was adopted for meta-analysis. All meta-analyses were performed by using STATA 12.0. Four RCTs with 264 patients were included in this meta-analysis. The current meta-analysis showed that there were significant differences in terms of visual analogue scale (VAS) scores and WOMAC scores at 1 week, 4weeks and 7 weeks compared with control groups. However, leech therapy was associated with a significantly higher incidence of adverse events. The overall evidence quality is moderate, which means that further research is likely to significantly change confidence in the effect estimate but may change the estimate. Medical leech therapy was associated with a significantly improved outcome in pain relief and functional recovery in patients with symptomatic knee OA. However, given the inherent limitations in the included studies, this conclusion should be interpreted cautiously. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

No common denominator: a review of outcome measures in IVF RCTs.

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Wilkinson, Jack; Roberts, Stephen A; Showell, Marian; Brison, Daniel R; Vail, Andy

2016-12-01

Which outcome measures are reported in RCTs for IVF? Many combinations of numerator and denominator are in use, and are often employed in a manner that compromises the validity of the study. The choice of numerator and denominator governs the meaning, relevance and statistical integrity of a study's results. RCTs only provide reliable evidence when outcomes are assessed in the cohort of randomised participants, rather than in the subgroup of patients who completed treatment. Review of outcome measures reported in 142 IVF RCTs published in 2013 or 2014. Trials were identified by searching the Cochrane Gynaecology and Fertility Specialised Register. English-language publications of RCTs reporting clinical or preclinical outcomes in peer-reviewed journals in the period 1 January 2013 to 31 December 2014 were eligible. Reported numerators and denominators were extracted. Where they were reported, we checked to see if live birth rates were calculated correctly using the entire randomised cohort or a later denominator. Over 800 combinations of numerator and denominator were identified (613 in no more than one study). No single outcome measure appeared in the majority of trials. Only 22 (43%) studies reporting live birth presented a calculation including all randomised participants or only excluding protocol violators. A variety of definitions were used for key clinical numerators: for example, a consensus regarding what should constitute an ongoing pregnancy does not appear to exist at present. Several of the included articles may have been secondary publications. Our categorisation scheme was essentially arbitrary, so the frequencies we present should be interpreted with this in mind. The analysis of live birth denominators was post hoc. There is massive diversity in numerator and denominator selection in IVF trials due to its multistage nature, and this causes methodological frailty in the evidence base. The twin spectres of outcome reporting bias and analysis of non

Contrast-induced nephropathy in patients with diabetes mellitus between iso- and low-osmolar contrast media: A meta-analysis of full-text prospective, randomized controlled trials.

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Han, Xiao-Fang; Zhang, Xin-Xiu; Liu, Ke-Mei; Tan, Hua; Zhang, Qiu

2018-01-01

This study was conducted to compare iso-osmolar contrast medium, iodixanol, with low-osmolar contrast media (LOCM) for assessing contrast-induced nephropathy (CIN) incidence, exclusively in the diabetic population. A systematic search was conducted for full-text, prospective, randomized controlled trials (RCTs). The primary outcome was incidence of CIN. Medline, Cochrane Central Register of Controlled Trials, and other sources were searched until May 31, 2017. Twelve RCTs finally met the search criteria. Iodixanol did not significantly reduce the risk of CIN (risk ratio [RR]: 0.72, 95% confidence interval (CI): [0.49, 1.04], p = 0.08). However, there was significantly reduced risk of CIN when iodixanol was compared to a LOCM agent iohexol (RR: 0.32, 95% CI [0.12, 0.89]). There were no differences between iodixanol and the other non-iohexol LOCM (RR: 0.92, 95% CI [0.68, 1.25]). In diabetic populations, iodixanol is not associated with a significant reduction of CIN risk. Iodixanol is associated with a reduced risk of CIN compared with iohexol, whereas no significant difference between iodixanol and other LOCM could be found.

Are the Cochrane group registers comprehensive? A case study of Japanese psychiatry trials

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McGuire Hugh

2002-04-01

Full Text Available Abstract Background Language bias is a form of publication bias and constitutes a serious threat to meta-analyses. The Cochrane Controlled Trials Register is one attempt to remedy this and now contains more than 300,000 citations. However we are still unsure if it provides comprehensive coverage, particularly for non-English trials. Methods We have recently established a comprehensive register of Japanese trials of psychotropic drugs through extensive personal contacts, electronic searches and handsearches. We examined two Cochrane psychiatry group registers against this Japanese database. Results The Japanese register contained 56 reports of randomized controlled trials (RCTs of antidepressants for depression but the Cochrane Depression, Anxiety and Neurosis group register contained 18, with an overlap of only nine. The Japanese register contained 61 reports of RCTs of neuroleptics for schizophrenia and the Cochrane Schizophrenia group register contained 36, with an overlap of only six. Taking account of some duplicate publications, only a quarter to a third of all relevant Japanese RCTs were retrievable from the Cochrane group registers. Conclusions Similar, or worse, yields may be expected with RCTs conducted in other East Asian countries, and in other fields of medicine. What evidence there is suggests that this situation may lead to a systematic over estimate of treatment effect.

Dairy Intake Enhances Body Weight and Composition Changes during Energy Restriction in 18–50-Year-Old Adults—A Meta-Analysis of Randomized Controlled Trials

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Welma Stonehouse

2016-07-01

Full Text Available Background/Aims: A meta-analysis of randomized controlled trials (RCTs was performed to investigate the effects of dairy food or supplements during energy restriction on body weight and composition in 18–50-year-old. Methods: RCTs ≥ 4 weeks comparing the effect of dairy consumption (whole food or supplements with control diets lower in dairy during energy restriction on body weight, fat and lean mass were identified by searching MEDLINE, EMBASE, Pubmed, Cochrane Central and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP until March 2016. Reports were identified and critically appraised in duplicate. Data were pooled using random-effects meta-analysis. Chi2- and I2-statistics indicated heterogeneity. Dose effect was assessed using meta-regression analysis. GRADE guidelines were used to rate the quality (QR of the evidence considering risk of bias, inconsistency, indirectness, imprecision, publication bias and effect estimates. Results: 27 RCTs were reviewed. Participants consumed between 2 and 4 standard servings/day of dairy food or 20–84 g/day of whey protein compared to low dairy control diets, over a median of 16 weeks. A greater reduction in body weight (−1.16 kg [−1.66, −0.66 kg], p < 0.001, I2 = 11%, QR = high, n = 644 and body fat mass (−1.49 kg [−2.06, −0.92 kg], p < 0.001, I2 = 21%, n = 521, QR = high were found in studies largely including women (90% women. These effects were absent in studies that imposed resistance training (QR = low-moderate. Dairy intake resulted in smaller loss of lean mass (all trials pooled: 0.36 kg [0.01, 0.71 kg], p = 0.04, I2 = 64%, n = 651, QR = moderate. No between study dose-response effects were seen. Conclusions: Increased dairy intake as part of energy restricted diets resulted in greater loss in bodyweight and fat mass while attenuating lean mass loss in 18–50-year-old adults. Further research in males is needed to investigate sex effects.

Sexual risk reduction for HIV-infected persons: a meta-analytic review of "positive prevention" randomized clinical trials.

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Yin, Lu; Wang, Na; Vermund, Sten H; Shepherd, Bryan E; Ruan, Yuhua; Shao, Yiming; Qian, Han-Zhu

2014-01-01

Prevention intervention trials have been conducted to reduce risk of sexual transmission among people living with HIV/AIDS (PLWHA), but the findings were inconsistent. We performed a systematic review and meta-analysis to evaluate overall efficacy of prevention interventions on unprotected vaginal or anal intercourse (UVAI) among PLWHA from randomized clinical trials (RCTs). RCTs of prevention interventions among PLWHA published as of February 2012 were identified by systematically searching thirteen electronic databases. The primary outcome was UVAI. The difference of standardized mean difference (SMD) of UVAI between study arms, defined as effect size (ES), was calculated for each study and then pooled across studies using standard meta-analysis with a random effects model. Lower likelihood of UVAI was observed in the intervention arms compared with the control arms either with any sexual partners (mean ES: -0.22; 95% confidence interval [CI]: -0.32, -0.11) or with HIV-negative or unknown-status sexual partners (mean ES and 95% CI: -0.13 [-0.22, -0.04]). Short-term efficacy of interventions with ≤ 10 months of follow up was significant in reducing UVAI (1-5 months: -0.27 [-0.45, -0.10]; 6-10 months: -0.18 [-0.30, -0.07]), while long-term efficacy of interventions was weaker and might have been due to chance (11-15 months: -0.13 [-0.34, 0.08]; >15 months: -0.05 [-0.43, 0.32]). Our meta-analyses confirmed the short-term impact of prevention interventions on reducing self-reported UVAI among PLWHA irrespective of the type of sexual partner, but did not support a definite conclusion on long-term effect. It is suggested that booster intervention sessions are needed to maintain a sustainable reduction of unprotected sex among PLWHA in future risk reduction programs.

Effect of dietary fiber on circulating C-reactive protein in overweight and obese adults: a meta-analysis of randomized controlled trials.

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Jiao, Jun; Xu, Jia-Ying; Zhang, Weiguo; Han, Shufen; Qin, Li-Qiang

2015-02-01

Previous studies suggested that dietary fiber intake may have a lowing effect on circulating C-reactive protein (CRP) level, a sensitive marker of inflammation, in overweight/obese adults with inconsistent results. A literature search was performed in April 2014 for related randomized controlled trials (RCTs) and meta-analysis was conducted. Meta-analysis including 14 RCTs showed that intervention with dietary fiber or fiber-rich food, compared with control, produced a slight, but significant reduction of 0.37 mg/L (95% CI -0.74, 0) in circulating CRP level among this population. Subgroup analyses showed that such a significant reduction was only observed after combining studies where the total fiber intake was 8 g/d higher in the intervention group than in the control group. No obvious heterogeneity and publication bias were found in the meta-analysis. In conclusion, this meta-analysis provides evidence that dietary fiber or food naturally rich in fiber has beneficial effects on circulating CRP level in overweight/obese adults.

Quetiapine monotherapy in acute treatment of generalized anxiety disorder: a systematic review and meta-analysis of randomized controlled trials

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Maneeton N

2016-01-01

Full Text Available Narong Maneeton,1 Benchalak Maneeton,1 Pakapan Woottiluk,2 Surinporn Likhitsathian,1 Sirijit Suttajit,1 Vudhichai Boonyanaruthee,1 Manit Srisurapanont1 1Department of Psychiatry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Psychiatric Nursing Division, Faculty of Nursing, Chiang Mai University, Chiang Mai, Thailand Background: Some studies have indicated the efficacy of quetiapine in the treatment of generalized anxiety disorder (GAD.Objective: The purpose of this study was to systematically review the efficacy, acceptability, and tolerability of quetiapine in adult patients with GAD.Methods: The SCOPUS, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched in April 2015. All randomized controlled trials (RCTs of GAD were considered to be included in this meta-analysis. All RCTs of quetiapine in GAD patients providing endpoint outcomes relevant to severity of anxiety, response rate, remission rate, overall discontinuation rate, or discontinuation rate due to adverse events were included. The version reports from suitable clinical studies were explored, and the important data were extracted. Measurement for efficacy outcomes consisted of the mean-changed scores of the rating scales for anxiety, and response rate.Results: A total of 2,248 randomized participants in three RCTs were included. The pooled mean-changed score of the quetiapine-treated group was greater than that of the placebo-treated group and comparable to selective serotonin reuptake inhibitors (SSRIs. Unfortunately, the response and the remission rates in only 50 and 150 mg/day of quetiapine-XR (extended-release were better than those of the placebo. Their response and remission rates were comparable to SSRIs. The rates of pooled overall discontinuation and discontinuation due to adverse events of quetiapine-XR were greater than placebo. Only the overall discontinuation rate of quetiapine-XR at 50 and

The Traditional Chinese Medicine and Relevant Treatment for the Efficacy and Safety of Atopic Dermatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Shi, Zhao-feng; Song, Tie-bing; Xie, Juan; Yan, Yi-quan

2017-01-01

Background Atopic dermatitis (AD) has become a common skin disease that requires systematic and comprehensive treatment to achieve adequate clinical control. Traditional Chinese medicines and related treatments have shown clinical effects for AD in many studies. But the systematic reviews and meta-analyses for them are lacking. Objective The systematic review and meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement were conducted to evaluate the efficacy and safety of traditional Chinese medicines and related treatments for AD treatment. Methods Randomized controlled trials (RCTs) were searched based on standardized searching rules in eight medical databases from the inception up to December 2016 and a total of 24 articles with 1,618 patients were enrolled in this meta-analysis. Results The results revealed that traditional Chinese medicines and related treatments did not show statistical differences in clinical effectiveness, SCORAD amelioration, and SSRI amelioration for AD treatment compared with control group. However, EASI amelioration of traditional Chinese medicines and related treatments for AD was superior to control group. Conclusion We need to make conclusion cautiously for the efficacy and safety of traditional Chinese medicine and related treatment on AD therapy. More standard, multicenter, double-blind randomized controlled trials (RCTs) of traditional Chinese medicine and related treatment for AD were required to be conducted for more clinical evidences providing in the future. PMID:28713436

Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials.

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Benjamin Kasenda

2016-06-01

Full Text Available Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i the existence and types of publication agreements in trial protocols, (ii the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii the frequency of co-authorship by industry employees.We used a retrospective cohort of randomized clinical trials (RCTs based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5% mentioned an agreement regarding publication of results. Of these 456, 393 (86.2% documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6% agreements were without constraints of publication. The remaining 24 (5.3% protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0% trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]. Of 71 agreements reported in publications, 52 (73.2% were concordant with those documented in the protocol. In 14 of 37 (37.8% publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements.Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do

Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials

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Kasenda, Benjamin; von Elm, Erik; You, John J.; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J.; Stegert, Mihaela; Olu, Kelechi K.; Tikkinen, Kari A. O.; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M.; Mertz, Dominik; Akl, Elie A.; Bassler, Dirk; Busse, Jason W.; Nordmann, Alain; Gloy, Viktoria; Ebrahim, Shanil; Schandelmaier, Stefan; Sun, Xin; Vandvik, Per O.; Johnston, Bradley C.; Walter, Martin A.; Burnand, Bernard; Hemkens, Lars G.; Bucher, Heiner C.; Guyatt, Gordon H.; Briel, Matthias

2016-01-01

Background Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. Methods and Findings We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner’s right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. Conclusions Publication agreements constraining academic authors’ independence are common. Journal articles seldom report on

Differences in Funding Sources of Phase III Oncology Clinical Trials by Treatment Modality and Cancer Type.

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Jairam, Vikram; Yu, James B; Aneja, Sanjay; Wilson, Lynn D; Lloyd, Shane

2017-06-01

Given the limited resources available to conduct clinical trials, it is important to understand how trial sponsorship differs among different therapeutic modalities and cancer types and to consider the ramifications of these differences. We searched clinicaltrials.gov for a cross-sectional register of active, phase III, randomized controlled trials (RCTs) studying treatment-related endpoints such as survival and recurrence for the 24 most prevalent malignancies. We classified the RCTs into 7 categories of therapeutic modality: (1) chemotherapy/other cancer-directed drugs, (2) targeted therapy, (3) surgery, (4) radiation therapy (RT), (5) RT with other modalities, (6) multimodality therapy without RT, and (7) other. RCTs were categorized as being funded by one or more of the following groups: (1) government, (2) hospital/university, (3) industry, and (4) other. χ analysis was performed to detect differences in funding source distribution between modalities and cancer types. The percentage of multimodality trials (5%) and radiation RCTs (4%) funded by industry was less than that for chemotherapy (32%, Pfunding than any of the other modalities (Pfunded by industry if they also studied targeted therapy (Pfunded by industry than trials studying multimodality therapy or radiation. The impact of industry funding versus institutional or governmental sources of funding for cancer research is unclear and requires further study.

Adrenaline for out-of-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials.

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Lin, Steve; Callaway, Clifton W; Shah, Prakesh S; Wagner, Justin D; Beyene, Joseph; Ziegler, Carolyn P; Morrison, Laurie J

2014-06-01

The evidence for adrenaline in out-of-hospital cardiac arrest (OHCA) resuscitation is inconclusive. We systematically reviewed the efficacy of adrenaline for adult OHCA. We searched in MEDLINE, EMBASE, and Cochrane Library from inception to July 2013 for randomized controlled trials (RCTs) evaluating standard dose adrenaline (SDA) to placebo, high dose adrenaline (HDA), or vasopressin (alone or combination) in adult OHCA patients. Meta-analyses were performed using random effects modeling. Subgroup analyses were performed stratified by cardiac rhythm and by number of drug doses. The primary outcome was survival to discharge and the secondary outcomes were return of spontaneous circulation (ROSC), survival to admission, and neurological outcome. Fourteen RCTs (n=12,246) met inclusion criteria: one compared SDA to placebo (n=534), six compared SDA to HDA (n=6174), six compared SDA to an adrenaline/vasopressin combination (n=5202), and one compared SDA to vasopressin alone (n=336). There was no survival to discharge or neurological outcome differences in any comparison group, including subgroup analyses. SDA showed improved ROSC (RR 2.80, 95%CI 1.78-4.41, padrenaline. There was no benefit of adrenaline in survival to discharge or neurological outcomes. There were improved rates of survival to admission and ROSC with SDA over placebo and HDA over SDA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effect of the Mediterranean diet on cognition and brain morphology and function: a systematic review of randomized controlled trials.

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Radd-Vagenas, Sue; Duffy, Shantel L; Naismith, Sharon L; Brew, Bruce J; Flood, Victoria M; Fiatarone Singh, Maria A

2018-03-01

Observational studies of the Mediterranean diet suggest cognitive benefits, potentially reducing dementia risk. We performed the first published review to our knowledge of randomized controlled trials (RCTs) investigating Mediterranean diet effects on cognition or brain morphology and function, with an additional focus on intervention diet quality and its relation to "traditional" Mediterranean dietary patterns. We searched 9 databases from inception (final update December 2017) for RCTs testing a Mediterranean compared with alternate diet for cognitive or brain morphology and function outcomes. Analyses were based on 66 cognitive tests and 1 brain function outcome from 5 included studies (n = 1888 participants). The prescribed Mediterranean diets varied considerably between studies, particularly with regards to quantitative food advice. Only 8/66 (12.1%) of individual cognitive outcomes at trial level significantly favored a Mediterranean diet for cognitive performance, with effect sizes (ESs) ranging from small (0.32) to large (1.66), whereas 2 outcomes favored controls. Data limitations precluded a meta-analysis. Of 8 domain composite cognitive scores from 2 studies, the 3 (Memory, Frontal, and Global function) from PREDIMED (PREvención con DIeta MEDiterránea) were significant, with ESs ranging from 0.39 to 1.29. A posttest comparison at a second PREDIMED site found that the Mediterranean diet modulates the effect of several genotypes associated with dementia risk for some cognitive outcomes, with mixed results. Finally, the risk of low-plasma brain-derived neurotrophic factor was reduced by 78% (OR = 0.22; 95% CI: 0.05, 0.90) in those who consumed a Mediterranean diet compared to control diet at 3 y in this trial. There was no benefit of the Mediterranean diet for incident cognitive impairment or dementia. Five RCTs of the Mediterranean diet and cognition have been published to date. The data are mostly nonsignificant, with small ESs. However, the

INTERBED: internet-based guided self-help for overweight and obese patients with full or subsyndromal binge eating disorder. A multicenter randomized controlled trial

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de Zwaan Martina

2012-11-01

Full Text Available Abstract Background Binge eating disorder (BED is a prevalent clinical eating disorder associated with increased psychopathology, psychiatric comorbidity, overweight and obesity, and increased health care costs. Since its inclusion in the DSM-IV, a few randomized controlled trials (RCTs have suggested efficacy of book-based self-help interventions in the treatment of this disorder. However, evidence from larger RCTs is needed. Delivery of self-help through new technologies such as the internet should be investigated in particular, as these approaches have the potential to be more interactive and thus more attractive to patients than book-based approaches. This study will evaluate the efficacy of an internet-based guided self-help program (GSH-I and cognitive-behavioral therapy (CBT, which has been proven in several studies to be the gold standard treatment for BED, in a prospective multicenter randomized trial. Methods The study assumes the noninferiority of GSH-I compared to CBT. Both treatments lasted 4 months, and maintenance of outcome will be assessed 6 and 18 months after the end of treatment. A total of 175 patients with BED and a body mass index between 27 and 40 kg/m2 were randomized at 7 centers in Germany and Switzerland. A 20% attrition rate was assumed. As in most BED treatment trials, the difference in the number of binge eating days over the past 28 days is the primary outcome variable. Secondary outcome measures include the specific eating disorder psychopathology, general psychopathology, body weight, quality of life, and self-esteem. Predictors and moderators of treatment outcome will be determined, and the cost-effectiveness of both treatment conditions will be evaluated. Results The methodology for the INTERBED study has been detailed. Conclusions Although there is evidence that CBT is the first-line treatment for BED, it is not widely available. As BED is still a recent diagnostic category, many cases likely remain

Reporting of conflicts of interests in meta-analyses of trials of pharmacological treatments

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Roseman, M.; Milette, K.; Bero, A.B.; Coyne, J.C.; Lexchin, J.; Turner, E.H.; Thombs, B.D.

2011-01-01

Abstract CONTEXT: Disclosure of conflicts of interest (COIs) from pharmaceutical industry study funding and author-industry financial relationships is sometimes recommended for randomized controlled trials (RCTs) published in biomedical journals. Authors of meta-analyses, however, are not required

Could ginseng-based medicines be better than nitrates in treating ischemic heart disease? A systematic review and meta-analysis of randomized controlled trials.

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Jia, Yongliang; Zhang, Shikai; Huang, Fangyi; Leung, Siu-wai

2012-06-01

Ginseng-based medicines and nitrates are commonly used in treating ischemic heart disease (IHD) angina pectoris in China. Hundreds of randomized controlled trials (RCTs) reported in Chinese language claimed that ginseng-based medicines can relieve the symptoms of IHD. This study provides the first PRISMA-compliant systematic review with sensitivity and subgroup analyses to evaluate the RCTs comparing the efficacies of ginseng-based medicines and nitrates in treating ischemic heart disease, particularly angina pectoris. Past RCTs published up to 2010 on ginseng versus nitrates in treating IHD for 14 or more days were retrieved from major English and Chinese databases, including PubMed, Science Direct, Cochrane Library, WangFang Data, and Chinese National Knowledge Infrastructure. The qualities of included RCTs were assessed with Jadad scale, a refined Jadad scale called M scale, CONSORT 2010 checklist, and Cochrane risk of bias tool. Meta-analysis was performed on the primary outcomes including the improvement of symptoms and electrocardiography (ECG). Subgroup analysis, sensitivity analysis, and meta-regression were performed to evaluate the effects of study characteristics of RCTs, including quality, follow-up periods, and efficacy definitions on the overall effect size of ginseng. Eighteen RCTs with 1549 participants were included. Overall odds ratios for comparing ginseng-based medicines with nitrates were 3.00 (95% CI: 2.27-3.96) in symptom improvement (n=18) and 1.61 (95% CI: 1.20-2.15) in ECG improvement (n=10). Subgroup analysis, sensitivity analysis, and meta-regression found no significant difference in overall effects among all study characteristics, indicating that the overall effects were stable. The meta-analysis of 18 eligible RCTs demonstrates moderate evidence that ginseng is more effective than nitrates for treating angina pectoris. However, further RCTs for higher quality, longer follow-up periods, lager sample size, multi-center/country, and are

Aromatherapy for the Treatment of Patients with Behavioral and Psychological Symptoms of Dementia: A Descriptive Analysis of RCTs.

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Press-Sandler, Olga; Freud, Tamar; Volkov, Ilya; Peleg, Roni; Press, Yan

2016-06-01

Behavioral and psychological symptoms of dementia (BPSD) are a common problem among patients with dementia. This problem is usually treated by drugs, but they have limited efficacy and often cause adverse effects. Aromatherapy is a nonpharmacologic treatment that is simple to use and devoid of significant adverse effects. To review the literature on the effectiveness of aromatherapy treatment in patients with BPSD. A descriptive analysis of randomized clinical trials (RCTs) published in the English-language literature and cited in PubMed. Eleven articles on RCTs were found, of which 1 had fewer than 10 participants, 2 were mistakenly presented as RCTs, and another did not report treatment for BPSD. In all, 7 articles with 417 participants total (range, 15-114) were reviewed. The mean age in all studies was greater than 69 years (range, 69-85 years), and the percentage of women was 55% (range, 50%-57%). The intervention period ranged from 10 days to 12 weeks. Two studies used Melissa oil and 5 others used lavender oil. The studies described different methods of administration for the oils, including spraying and rubbing over various body organs. The duration of treatment differed among the studies. In 3 studies the investigators concluded that the treatment was not effective and in 3 that it was effective; in 1 study no clear conclusion could be drawn. The difference between positive and negative studies was not explained by differences in the study population, the type of oil, or the duration of treatment. The significant difference apparently stems from the method of administration. When the oil was applied close to the olfactory system the outcome was positive. A study should be designed to assess the effect of the site of application of aromatherapy.

Impact of patient position on the incidence of ventilator-associated pneumonia: a meta-analysis of randomized controlled trials.

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Alexiou, Vangelis G; Ierodiakonou, Vrettos; Dimopoulos, George; Falagas, Matthew E

2009-12-01

The aim of this study is to summarize the effect of position (prone and semirecumbent 45 degrees ) of mechanically ventilated patients on the incidence of ventilator-associated pneumonia (VAP) and other outcomes. A systematic search for randomized control trials (RCTs) was done. We estimated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using fixed effects model or random effects model, where appropriate. For continuous variables, we calculated the estimation of weighted mean differences. We analyzed data extracted from 3 RCTs studying the semirecumbent 45 degrees and 4 RCTs studying the prone position with a total of 337 and 1018 patients, respectively. The odds of developing clinically diagnosed VAP were significantly lower among patients in the semirecumbent 45 degrees position compared to patients in the supine position (OR = 0.47; 95% CI, 0.27-0.82; 337 patients). The comparison of prone vs supine position group showed a moderate trend toward better outcomes regarding the incidence of clinically diagnosed VAP among patients in the prone position (OR = 0.80; 95% CI, 0.60-1.08; 1018 patients). The subanalysis regarding the incidence of microbiologically documented VAP, the length of intensive care unit stay, and the duration of mechanical ventilation showed that patients in the semirecumbent 45 degrees position have a moderate trend toward better clinical outcomes. This meta-analysis provides additional evidence that the usual practice of back-rest elevation of 15 degrees to 30 degrees is not sufficient to prevent VAP in mechanically ventilated patients. Patients positioned semirecumbently 45 degrees have significantly lower incidence of clinically diagnosed VAP compared to patients positioned supinely. On the other hand, the incidence of clinically diagnosed VAP among patients positioned pronely does not differ significantly from the incidence of clinically diagnosed VAP among patients positioned supinely.

Reporting of Conflicts of Interest in Meta-analyses of Trials of Pharmacological Treatments

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Roseman, Michelle; Milette, Katherine; Bero, Lisa A.; Coyne, James C.; Lexchin, Joel; Turner, Erick H.; Thombs, Brett D.

2011-01-01

Context Disclosure of conflicts of interest (COIs) from pharmaceutical industry study funding and author-industry financial relationships is sometimes recommended for randomized controlled trials (RCTs) published in biomedical journals. Authors of meta-analyses, however, are not required to report

Methodological issues for designing and conducting a multicenter, international clinical trial in Acute Stroke: Experience from ARTSS-2 trial.

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Rahbar, Mohammad H; Dickerson, Aisha S; Cai, Chunyan; Pedroza, Claudia; Hessabi, Manouchehr; Shen, Loren; Pandurengan, Renganayaki; Jacobs, Amber Nicole M; Indupuru, Hari; Sline, Melvin R; Delgado, Rigoberto I; Macdonald, Claire; Ford, Gary A; Grotta, James C; Barreto, Andrew D

2015-09-01

We describe innovations in the study design and the efficient data coordination of a randomized multicenter trial of Argatroban in Combination with Recombinant Tissue Plasminogen Activator for Acute Stroke (ARTSS-2). ARTSS-2 is a 3-arm, multisite/multiregional randomized controlled trials (RCTs) of two doses of Argatroban injection (low, high) in combination with recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke patients and rt-PA alone. We developed a covariate adaptive randomization program that balanced the study arms with respect to study site as well as hemorrhage after thrombolysis (HAT) score and presence of distal internal carotid artery occlusion (DICAO). We used simulation studies to validate performance of the randomization program before making any adaptations during the trial. For the first 90 patients enrolled in ARTSS-2, we evaluated performance of our randomization program using chi-square tests of homogeneity or extended Fisher's exact test. We also designed a four-step partly Bayesian safety stopping rule for low and high dose Argatroban arms. Homogeneity of the study arms was confirmed with respect to distribution of study site (UK sites vs. US sites, P=0.98), HAT score (0-2 vs. 3-5, P=1.0), and DICAO (N/A vs. No vs. Yes, P=0.97). Our stopping thresholds for safety of low and high dose Argatroban were not crossed. Despite challenges, data quality was assured. We recommend adaptive designs for randomization and Bayesian safety stopping rules for multisite Phase I/II RCTs for maintaining additional flexibility. Efficient data coordination could lead to improved data quality. Copyright © 2015. Published by Elsevier Inc.

Assessing the risk of bias in randomized controlled trials in the field of dentistry indexed in the Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) database.

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Ferreira, Christiane Alves; Loureiro, Carlos Alfredo Salles; Saconato, Humberto; Atallah, Alvaro Nagib

2011-03-01

Well-conducted randomized controlled trials (RCTs) represent the highest level of evidence when the research question relates to the effect of therapeutic or preventive interventions. However, the degree of control over bias between RCTs presents great variability between studies. For this reason, with the increasing interest in and production of systematic reviews and meta-analyses, it has been necessary to develop methodology supported by empirical evidence, so as to encourage and enhance the production of valid RCTs with low risk of bias. The aim here was to conduct a methodological analysis within the field of dentistry, regarding the risk of bias in open-access RCTs available in the Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) database. This was a methodology study conducted at Universidade Federal de São Paulo (Unifesp) that assessed the risk of bias in RCTs, using the following dimensions: allocation sequence generation, allocation concealment, blinding, and data on incomplete outcomes. Out of the 4,503 articles classified, only 10 studies (0.22%) were considered to be true RCTs and, of these, only a single study was classified as presenting low risk of bias. The items that the authors of these RCTs most frequently controlled for were blinding and data on incomplete outcomes. The effective presence of bias seriously weakened the reliability of the results from the dental studies evaluated, such that they would be of little use for clinicians and administrators as support for decision-making processes.

Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

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Gourgou-Bourgade, S; Cameron, D; Poortmans, P; Asselain, B; Azria, D; Cardoso, F; A'Hern, R; Bliss, J; Bogaerts, J; Bonnefoi, H; Brain, E; Cardoso, M J; Chibaudel, B; Coleman, R; Cufer, T; Dal Lago, L; Dalenc, F; De Azambuja, E; Debled, M; Delaloge, S; Filleron, T; Gligorov, J; Gutowski, M; Jacot, W; Kirkove, C; MacGrogan, G; Michiels, S; Negreiros, I; Offersen, B V; Penault Llorca, F; Pruneri, G; Roche, H; Russell, N S; Schmitt, F; Servent, V; Thürlimann, B; Untch, M; van der Hage, J A; van Tienhoven, G; Wildiers, H; Yarnold, J; Bonnetain, F; Mathoulin-Pélissier, S; Bellera, C; Dabakuyo-Yonli, T S

2015-05-01

Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Data sharing and reanalysis of randomized controlled trials in leading biomedical journals with a full data sharing policy: survey of studies published in The BMJ and PLOS Medicine

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Naudet, Florian; Sakarovitch, Charlotte; Janiaud, Perrine; Cristea, Ioana; Fanelli, Daniele; Moher, David

2018-01-01

Abstract Objectives To explore the effectiveness of data sharing by randomized controlled trials (RCTs) in journals with a full data sharing policy and to describe potential difficulties encountered in the process of performing reanalyses of the primary outcomes. Design Survey of published RCTs. Setting PubMed/Medline. Eligibility criteria RCTs that had been submitted and published by The BMJ and PLOS Medicine subsequent to the adoption of data sharing policies by these journals. Main outcome measure The primary outcome was data availability, defined as the eventual receipt of complete data with clear labelling. Primary outcomes were reanalyzed to assess to what extent studies were reproduced. Difficulties encountered were described. Results 37 RCTs (21 from The BMJ and 16 from PLOS Medicine) published between 2013 and 2016 met the eligibility criteria. 17/37 (46%, 95% confidence interval 30% to 62%) satisfied the definition of data availability and 14 of the 17 (82%, 59% to 94%) were fully reproduced on all their primary outcomes. Of the remaining RCTs, errors were identified in two but reached similar conclusions and one paper did not provide enough information in the Methods section to reproduce the analyses. Difficulties identified included problems in contacting corresponding authors and lack of resources on their behalf in preparing the datasets. In addition, there was a range of different data sharing practices across study groups. Conclusions Data availability was not optimal in two journals with a strong policy for data sharing. When investigators shared data, most reanalyses largely reproduced the original results. Data sharing practices need to become more widespread and streamlined to allow meaningful reanalyses and reuse of data. Trial registration Open Science Framework osf.io/c4zke. PMID:29440066

Piracetam for Aphasia in Post-stroke Patients: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

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Zhang, Jie; Wei, Ruili; Chen, Zhongqin; Luo, Benyan

2016-07-01

Aphasia is a common symptom in post-stroke patients. Piracetam is a commonly used nootropic agent that promises various benefits to brain function, including language improvement. We performed a systematic review and meta-analysis to assess whether piracetam facilitates the rehabilitation of language performance in post-stroke patients. Randomized controlled trials (RCTs) of piracetam treatment in post-stroke patients published in any language were included, excluding those involving pre-existing cognitive disorders such as dementia and mood disturbances. We searched several databases including PubMed, EMBASE, Cochrane Central, CINAHL, Web of Science, and PsycINFO for RCTs published up to 31 December 2015. We conducted a meta-analysis using RevMan (version 5.3), with standardized mean differences (SMDs) and fixed-effect models, and used StataSE (version 13) for the detection of publication bias. This study has been submitted to PROSPERO, and its registration number is CRD42016034088. We identified 1180 titles and abstracts, and finally included seven RCTs in this meta-analysis. The number of participants in each study ranged from 19 to 66, summing up to 261 patients overall. The dose of piracetam was consistent while the frequency and time of therapy varied. The assessment of the language at the end of trials showed no significant improvement in overall severity of aphasia [SMD 0.23, 95 % confidence interval (CI) -0.03 to 0.49, P = 0.08], but written language (SMD 0.35, 95 % CI 0.04 to 0.66, P = 0.03) showed pronounced improvement. Subgroup analyses indicated a dissociation of effectiveness between short- and long-term assessment in overall severity (P = 0.008, I (2) = 85.6 %) in terms of tests for subgroup differences, and a mild trend toward dissociation in written subtests (P = 0.30, I (2) = 5.1 %). Funnel plots and Egger's test identified no obvious publication bias in the primary variable. Piracetam plays a limited role in the rehabilitation of

Are obsessive-compulsive personality traits associated with a poor outcome in anorexia nervosa? A systematic review of randomized controlled trials and naturalistic outcome studies.

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Crane, Anna M; Roberts, Marion E; Treasure, Janet

2007-11-01

Obsessive-compulsive personality disorder (OCPD) traits are commonly associated with anorexia nervosa (AN). The aim of this review was to systematically search the literature to examine whether OCPD traits have an impact on the outcome of AN. A systematic electronic search of the literature (using Medline, PsycINFO, and the Cochrane Central Register of Controlled Trials) was undertaken to identify relevant publications (randomized controlled trials (RCT's) and naturalistic studies), until February 2006. Eleven prospective longitudinal studies and 12 RCT's met criteria for inclusion. A meta-analysis was not feasible as the studies were too heterogeneous. Just over half of published longitudinal studies found that OCPD traits were associated with a negative outcome in AN. Additionally, results from three RCTs suggested that these traits may moderate outcome. OCPD traits were reduced after treatment in five RCTs. There is tentative support to suggest that individuals with AN and concomitant OCPD traits have a poorer prognosis, and that these traits moderate outcome. A reduction in these traits may mediate this change. An individualized case formulation with treatment tailored to OCPD traits may improve the outcome of AN. (c) 2007 by Wiley Periodicals, Inc.

Baseline participant characteristics and risk for dropout from ten obesity randomized controlled trials: a pooled analysis of individual level data

Directory of Open Access Journals (Sweden)

Kathryn Ann Kaiser

2014-12-01

Full Text Available Introduction: Understanding participant demographic characteristics that inform the optimal design of obesity RCTs have been examined in few studies. The objective of this study was to investigate the association of individual participant characteristics and dropout rates (DORs in obesity randomized controlled trials (RCT by pooling data from several publicly available datasets for analyses. We comprehensively characterize DORs and patterns in obesity RCTs at the individual study level, and describe how such rates and patterns vary as a function of individual-level characteristics. Methods: We obtained and analyzed nine publicly-available, obesity RCT datasets that examined weight loss or weight gain prevention as a primary or secondary endpoint. Four risk factors for dropout were examined by Cox proportional hazards including sex, age, baseline BMI, and race/ethnicity. The individual study data were pooled in the final analyses with a random effect for study, and HR and 95% CIs were computed. Results: Results of the multivariate analysis indicated that the risk of dropout was significantly higher for females compared to males (HR= 1.24, 95% CI = 1.05, 1.46. Hispanics and Non-Hispanic blacks had a significantly higher dropout rate compared to non-Hispanic whites (HR= 1.62, 95% CI = 1.37, 1.91; HR= 1.22, 95% CI = 1.11, 1.35, respectively. There was a significantly increased risk of dropout associated with advancing age (HR= 1.02, 95% CI = 1.01, 1.02 and increasing BMI (HR= 1.03, 95% CI = 1.03, 1.04. Conclusion/Significance: As more studies may focus on special populations, researchers designing obesity RCTs may wish to oversample in certain demographic groups if attempting to match comparison groups based on generalized estimates of expected dropout rates, or otherwise adjust a priori power estimates. Understanding true reasons for dropout may require additional methods of data gathering not generally employed in obesity RCTs, e.g. time on

Add-On Effect of Chinese Herbal Medicine on Mortality in Myocardial Infarction: Systematic Review and Meta-Analysis of Randomized Controlled Trials

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Vincent C. H. Chung

2013-01-01

Full Text Available In China, Chinese herbal medicine (CHM is widely used as an adjunct to biomedicine (BM in treating myocardial infarction (MI. This meta-analysis of RCTs evaluated the efficacy of combined CHM-BM in the treatment of MI, compared to BM alone. Sixty-five RCTs (12,022 patients of moderate quality were identified. 6,036 patients were given CHM plus BM, and 5,986 patients used BM only. Combined results showed clear additional effect of CHM-BM treatment in reducing all-cause mortality (relative risk reduction (RRR = 37%, 95% CI = 28%–45%, I2=0.0% and mortality of cardiac origin (RRR = 39%, 95% CI = 22%–52%, I2=22.8. Benefits remained after random-effect trim and fill adjustment for publication bias (adjusted RRR for all-cause mortality = 29%, 95% CI = 16%–40%; adjusted RRR for cardiac death = 32%, 95% CI = 15%–46%. CHM is also found to be efficacious in lowering the risk of fatal and nonfatal cardiogenic shock, cardiac arrhythmia, myocardial reinfarction, heart failure, angina, and occurrence of total heart events. In conclusion, addition of CHM is very likely to be able to improve survival of MI patients who are already receiving BM. Further confirmatory evaluation via large blinded randomized trials is warranted.

Glyceryl trinitrate for prevention of post-ERCP pancreatitis and improve the rate of cannulation: a meta-analysis of prospective, randomized, controlled trials.

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Jiexia Ding

Full Text Available BACKGROUND: Acute pancreatitis is the most common complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP. Several clinical trials used glyceryl trinitrate (GTN to prevent the incidence of post-ERCP pancreatitis (PEP. However, the results were still controversial. OBJECTIVE: To conduct a meta-analysis of published, full-length, randomized controlled trials evaluating the effect of prophylactic GTN on the prevention of PEP, improve the rate of cannulation and the prevention of hyperamylasemia. METHODS: Literature searches were conducted using PubMed, EMBASE, The Cochrane Library and Web of Knowledge databases, using keywords "post-ERCP" and "pancreatitis" and limited in randomized controlled trials. RESULTS: Twelve RCTs involving 2649 patients were included. Eleven RCTs compared GTN with placebo for PEP prevention. Meta-analysis showed the overall incidence of PEP was significantly reduced by GTN treatment (RR 0.67; 95% CI, 0.52-0.87. Nevertheless, GTN administration did not decrease the incidence of moderate to severe PEP (RR 0.70; 95% CI, 0.42-1.15. Subgroup analyses revealed that GTN administered by sublingual was more effective than transdermal and topical in reducing the incidence of PEP. Besides, the prophylactic effect of GTN was far more obvious in the group of high PEP incidence than in the group of low PEP incidence. Additionally, the incidence of hyperamylasemia was significantly reduced by GTN treatment (RR 0.69; 95% CI, 0.54-0.90. No differences of the successful cannulation rate of bile ducts (RR 1.03; 95% CI, 0.99-1.06 attributable to GTN were observed. CONCLUSION: Prophylactic use of GTN reduced the overall incidence of PEP and hyperamylasemia. However, GTN was not helpful for the severity of PEP and the rate of cannulation.

Efficacy of Turmeric Extracts and Curcumin for Alleviating the Symptoms of Joint Arthritis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

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Daily, James W; Yang, Mini; Park, Sunmin

2016-08-01

Although turmeric and its curcumin-enriched extracts have been used for treating arthritis, no systematic review and meta-analysis of randomized clinical trials (RCTs) have been conducted to evaluate the strength of the research. We systemically evaluated all RCTs of turmeric extracts and curcumin for treating arthritis symptoms to elucidate the efficacy of curcuma for alleviating the symptoms of arthritis. Literature searches were conducted using 12 electronic databases, including PubMed, Embase, Cochrane Library, Korean databases, Chinese medical databases, and Indian scientific database. Search terms used were "turmeric," "curcuma," "curcumin," "arthritis," and "osteoarthritis." A pain visual analogue score (PVAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used for the major outcomes of arthritis. Initial searches yielded 29 articles, of which 8 met specific selection criteria. Three among the included RCTs reported reduction of PVAS (mean difference: -2.04 [-2.85, -1.24]) with turmeric/curcumin in comparison with placebo (P curcumin treatment (mean difference: -15.36 [-26.9, -3.77]; P = .009). Furthermore, there was no significant mean difference in PVAS between turmeric/curcumin and pain medicine in meta-analysis of five studies. Eight RCTs included in the review exhibited low to moderate risk of bias. There was no publication bias in the meta-analysis. In conclusion, these RCTs provide scientific evidence that supports the efficacy of turmeric extract (about 1000 mg/day of curcumin) in the treatment of arthritis. However, the total number of RCTs included in the analysis, the total sample size, and the methodological quality of the primary studies were not sufficient to draw definitive conclusions. Thus, more rigorous and larger studies are needed to confirm the therapeutic efficacy of turmeric for arthritis.

Enteral versus parenteral nutrition in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials.

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Elke, Gunnar; van Zanten, Arthur R H; Lemieux, Margot; McCall, Michele; Jeejeebhoy, Khursheed N; Kott, Matthias; Jiang, Xuran; Day, Andrew G; Heyland, Daren K

2016-04-29

Enteral nutrition (EN) is recommended as the preferred route for early nutrition therapy in critically ill adults over parenteral nutrition (PN). A recent large randomized controlled trial (RCT) showed no outcome differences between the two routes. The objective of this systematic review was to evaluate the effect of the route of nutrition (EN versus PN) on clinical outcomes of critically ill patients. An electronic search from 1980 to 2016 was performed identifying relevant RCTs. Individual trial data were abstracted and methodological quality of included trials scored independently by two reviewers. The primary outcome was overall mortality and secondary outcomes included infectious complications, length of stay (LOS) and mechanical ventilation. Subgroup analyses were performed to examine the treatment effect by dissimilar caloric intakes, year of publication and trial methodology. We performed a test of asymmetry to assess for the presence of publication bias. A total of 18 RCTs studying 3347 patients met inclusion criteria. Median methodological score was 7 (range, 2-12). No effect on overall mortality was found (1.04, 95 % CI 0.82, 1.33, P = 0.75, heterogeneity I(2) = 11 %). EN compared to PN was associated with a significant reduction in infectious complications (RR 0.64, 95 % CI 0.48, 0.87, P = 0.004, I(2) = 47 %). This was more pronounced in the subgroup of RCTs where the PN group received significantly more calories (RR 0.55, 95 % CI 0.37, 0.82, P = 0.003, I(2) = 0 %), while no effect was seen in trials where EN and PN groups had a similar caloric intake (RR 0.94, 95 % CI 0.80, 1.10, P = 0.44, I(2) = 0 %; test for subgroup differences, P = 0.003). Year of publication and methodological quality did not influence these findings; however, a publication bias may be present as the test of asymmetry was significant (P = 0.003). EN was associated with significant reduction in ICU LOS (weighted mean difference [WMD] -0.80, 95 % CI -1.23, -0.37, P = 0.0003, I(2

Breast Cancer Chemoprevention: A Network Meta-Analysis of Randomized Controlled Trials.

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Mocellin, Simone; Pilati, Pierluigi; Briarava, Marta; Nitti, Donato

2016-02-01

Several agents have been advocated for breast cancer primary prevention. However, few of them appear effective, the associated severe adverse effects limiting their uptake. We performed a comprehensive search for randomized controlled trials (RCTs) reporting on the ability of chemoprevention agents (CPAs) to reduce the incidence of primary breast carcinoma. Using network meta-analysis, we ranked CPAs based simultaneously on efficacy and acceptability (an inverse measure of toxicity). All statistical tests were two-sided. We found 48 eligible RCTs, enrolling 271 161 women randomly assigned to receive either placebo or one of 21 CPAs. Aromatase inhibitors (anastrozole and exemestane, considered a single CPA class because of the lack of between-study heterogeneity; relative risk [RR] = 0.468, 95% confidence interval [CI] = 0.346 to 0.634), arzoxifene (RR = 0.415, 95% CI = 0.253 to 0.682), lasofoxifene (RR = 0.208, 95% CI = 0.079 to 0.544), raloxifene (RR = 0.572, 95% CI = 0.372 to 0.881), tamoxifen (RR = 0.708, 95% CI = 0.595 to 0.842), and tibolone (RR = 0.317, 95% CI = 0.127 to 0.792) were statistically significantly associated with a therapeutic effect, which was restricted to estrogen receptor-positive tumors of postmenopausal women (except for tamoxifen, which is active also during premenopause). Network meta-analysis ranking showed that the new selective estrogen receptor modulators (SERMs) arzoxifene, lasofoxifene, and raloxifene have the best benefit-risk ratio. Aromatase inhibitors and tamoxifen ranked second and third, respectively. These results provide physicians and health care regulatory agencies with RCT-based evidence on efficacy and acceptability of currently available breast cancer CPAs; at the same time, we pinpoint how much work still remains to be done before pharmacological primary prevention becomes a routine option to reduce the burden of this disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For

Mobile access to virtual randomization for investigator-initiated trials.

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Deserno, Thomas M; Keszei, András P

2017-08-01

Background/aims Randomization is indispensable in clinical trials in order to provide unbiased treatment allocation and a valid statistical inference. Improper handling of allocation lists can be avoided using central systems, for example, human-based services. However, central systems are unaffordable for investigator-initiated trials and might be inaccessible from some places, where study subjects need allocations. We propose mobile access to virtual randomization, where the randomization lists are non-existent and the appropriate allocation is computed on demand. Methods The core of the system architecture is an electronic data capture system or a clinical trial management system, which is extended by an R interface connecting the R server using the Java R Interface. Mobile devices communicate via the representational state transfer web services. Furthermore, a simple web-based setup allows configuring the appropriate statistics by non-statisticians. Our comprehensive R script supports simple randomization, restricted randomization using a random allocation rule, block randomization, and stratified randomization for un-blinded, single-blinded, and double-blinded trials. For each trial, the electronic data capture system or the clinical trial management system stores the randomization parameters and the subject assignments. Results Apps are provided for iOS and Android and subjects are randomized using smartphones. After logging onto the system, the user selects the trial and the subject, and the allocation number and treatment arm are displayed instantaneously and stored in the core system. So far, 156 subjects have been allocated from mobile devices serving five investigator-initiated trials. Conclusion Transforming pre-printed allocation lists into virtual ones ensures the correct conduct of trials and guarantees a strictly sequential processing in all trial sites. Covering 88% of all randomization models that are used in recent trials, virtual randomization

Efficacy for Psychopathology and Body Weight and Safety of Topiramate-Antipsychotic Cotreatment in Patients With Schizophrenia Spectrum Disorders: Results From a Meta-Analysis of Randomized Controlled Trials.

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Correll, Christoph U; Maayan, Lawrence; Kane, John; Hert, Marc De; Cohen, Dan

2016-06-01

To meta-analyze the efficacy and tolerability of topiramate-antipsychotic cotreatment in schizophrenia. PubMed/MEDLINE database were searched until September 5, 2015, using the keywords topiramate AND antipsych* OR neurolept* OR specific antipsychotic names. Randomized controlled trials (RCTs) of topiramate-antipsychotic cotreatment versus placebo and ongoing antipsychotic treatment in patients with schizophrenia spectrum disorders were included. Two evaluators extracted data. Standardized mean difference (SMD), weighted mean difference (WMD), and risk ratio (RR) ± 95% CIs were calculated. In 8 RCTs, lasting a mean ± SD of 13.6 ± 4.9 weeks, 439 patients were randomized to topiramate (100-400 mg/d) versus placebo (trials = 7) or ongoing antipsychotic treatment (trial = 1). Topiramate outperformed the comparator regarding total psychopathology (trials = 6, n = 269, SMD = -0.57 [95% CI, -1.01 to -0.14], P = .01), positive symptoms (trials = 4, n = 190, SMD = -0.56 [95% CI, -1.0 to -0.11], P = .01), negative symptoms (trials = 4, n = 190, SMD = -0.62 [95% CI, -1.13 to -0.10], P = .02) general psychopathology (trials = 3, n = 179, SMD = -0.69 [95% CI, -1.27 to -0.11], P = .02), body weight (trials = 7, n = 327, WMD = -3.14 kg [95% CI, -5.55 to -0.73], P = .01), and body mass index (BMI) (trials = 4, n = 198, WMD = -1.80 [95% CI, -2.77 to -0.84], P = .0003). Topiramate's efficacy for total psychopathology and weight reduction effects were not mediated/moderated by trial duration, topiramate dose, sex, age, inpatient status, baseline Positive and Negative Syndrome Scale, or baseline BMI. Conversely, clozapine-topiramate cotreatment moderated greater efficacy, but less weight loss, compared to topiramate-nonclozapine antipsychotic combinations. All-cause discontinuation was similar between topiramate and control groups (trials = 7, RR = 1.24 [95% CI, 0.76 to 2.02], P = .39). Topiramate trended only toward more paresthesia than placebo (trials = 4, RR = 2.03 [95 % CI, 0

Transcatheter closure of patent foramen ovale for secondary prevention of ischemic stroke: Quantitative synthesis of pooled randomized trial data.

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Hakeem, Abdul; Cilingiroglu, Mehmet; Katramados, Angelos; Boudoulas, Konstantinos Dean; Iliescu, Cezar; Gundogdu, Betul; Marmagkiolis, Konstantinos

2018-01-14

To evaluate the safety and efficacy of percutaneous device closure of patent foramen ovale (PFO) for secondary prevention of ischemic stroke BACKGROUND: Stroke remains the leading cause of serious long-term disability in the United States. The effectiveness of a percutaneous PFO closure in the prevention of recurrent cryptogenic strokes has not been established. We performed a literature search using PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Google Scholar, and Internet-based sources from January 2003 to September 2017. Randomized controlled trails (RCTs) comparing percutaneous PFO closure to medical therapy alone. Five RCTs (CLOSURE I, PC Trial, REDUCE, RESPECT, and CLOSE) with 1,829 patients in the device group and 1,611 patients in the medical group met inclusion criteria. The cumulative incidence of recurrent stroke was 2.02% in the PFO closure arm and 4.4% in the medical therapy group (RR 0.42, 95%CI 0.20, 0.91; P = 0.03). There was no difference in the incidence of death [0.7% vs. 0.9%; RR 0.76 (95% CI 0.35, 1.64), P = 0.49] or adverse events during the follow-up period [24.6% vs. 23.7% (RR 1.03; 95% CI 0.91, 1.16), P = 0.65] between the closure and medical therapy groups. Incidence of atrial fibrillation was significantly higher in closure group compared to medical therapy [4% vs. 0.6% (RR 4.73; 95% CI 2.09, 10.70), P = 0.0002]. The comparative effectiveness of PFO closure (compared to medical therapy) was significantly more pronounced in those younger than 45 years, males, larger shunts and disc design platforms (P < 0.05). Based on the results of this analysis of randomized trial data, percutaneous PFO closure appears to be a safe and effective therapeutic option for the secondary prevention of ischemic stroke in patients with PFO and cryptogenic stroke. © 2018 Wiley Periodicals, Inc.

Have Recent Vertebroplasty Trials Changed the Indications for Vertebroplasty?

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Gangi, Afshin; Clark, William A.

2010-01-01

Two different investigators in the New England Journal of Medicine recently published two randomized controlled trials (RCTs) regarding the efficacy of vertebroplasty for painful osteoporotic vertebral compression fractures. In their results, both investigators concluded that there was no significant difference in pain relief between the vertebroplasty group and control group 1 month after treatment. The trials described a different patient cohort from the one we treat with vertebroplasty. Both enrolled patients had back pain for ≤12 months. This duration of pain was far too long for a vertebroplasty trial, resulting in parallel trials of vertebroplasty on healed fractures. Where a study is needed, it should be comprised of patients with acute osteoporotic compression fractures, particularly those who are hospitalized or bedridden because of the pain of such fractures. Magnetic resonance imaging was not systematically performed before vertebroplasty, and inpatients were excluded. Inpatients with acute fracture pain are the group most likely to respond well to vertebroplasty. Enrolment was a problem in both trials. Randomization in both RCTs took >4 years for completion. We advise that vertebroplasty be offered to patients with recent fractures <8 weeks old who have uncontrolled pain as well as patients progressing to osteonecrosis and the intravertebral vacuum phenomenon (Kummels disease). The availability of recent MRI scanning is also critical to proper patient selection.

Efficacy and Safety of Everolimus for Maintenance Immunosuppression of Kidney Transplantation: A Meta-Analysis of Randomized Controlled Trials.

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Jinyu Liu

Full Text Available Conversion to everolimus is often used in kidney transplantation to overcome calcineurin inhibitor (CNI nephrotoxicity but there is conflicting evidence for this approach.To investigate the benefits and harm from randomized clinical trials (RCTs involving the conversion from CNI to everolimus after kidney transplantation.Databases were searched up to March 2016. Two reviewers independently assessed trials for eligibility and quality, and extracted data. Results are expressed as risk ratio (RR or mean difference (MD with 95% confidence intervals (CI.Eleven RCTs, with a total of 1,633 patients, met the final inclusion criteria. Patients converted to everolimus had improved renal function at 1 year posttransplant with an estimated glomerular filtration rate (eGFR of 5.36 mL/min per 1.73 m2 greater than patients remaining on CNI (p = 0.0005 and the longer-term results (> 1 year of renal function was identical to that of 1 year. There was not a substantial difference in graft loss, mortality, and the occurrence of adverse events (AEs or serious AEs. However, the risks of acute rejection and trial termination due to AEs with everolimus are respectively 1.82 and 2.63 times greater than patients staying on CNI at 1 year posttransplant (p = 0.02, p = 0.03, respectively. Further, those patients who converted to everolimus had a substantially greater risk of anemia, hyperlipidemia, hypercholesterolemia, hypokalemia, proteinuria, stomatitis, mouth ulceration, and acne.Conversion from CNI to everolimus after kidney transplantation is associated with improved renal function in the first 5 years posttransplant but increases the risk of acute rejection at 1 year posttransplant and may not be well endured.

Misoprostol versus ergometrine-oxytocin for preventing postpartum haemorrhage: a systematic review and meta-analysis of randomized controlled trials.

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Tan, Jing; Cao, Qiao; He, Guo-Lin; Cai, Yu-Han; Yu, Jia-Jie; Sun, Xin; Li, You-Ping

2016-11-01

To compare the effects of misoprostol versus ergometrine-oxytocin for postpartum haemorrhage (PPH) prevention, and provide important evidence to choose optimal agents for preventing PPH in developing countries. The Cochrane Central Register of Controlled Trials, PubMed, EMbase, and ClinicalTrails.gov were searched from inception to 1st January 2016. Two authors independently extracted data and assessed risk of bias of studies according to Cochrane Handbook5.1.0. Meta-analysis was performed using RevMan5.2.4 software. A total of 4034 women from six randomized controlled trials (RCTs) were included. Meta-analyses showed that the PPH rate (7.6% vs. 4.2%, RR = 1.81, 95%CI (1.40, 2.35), P oxytocin group, respectively. But there was no significant difference of severe PPH rate between two groups (1.2% vs. 0.76%, RR = 1.55, 95%CI (0.78, 3.07), P = 0.21). The need for manual removal of placenta in misoprostol was only about one-third of ergometrine-oxytocin (0.5% vs. 1.4%, RR = 0.33, 95%CI (0.15, 0.76), P oxytocin could be deemed as alternative agent in low-resource setting due to recognized effect. As a result of limited evidence about these uterotonic agents, the more high-quality RCTs are needed to determine the potentials and harms of various uterotonic agents for preventing PPH in developing countries. © 2016 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

Efficacy and safety of oxcarbazepine in the treatment of children with epilepsy: a meta-analysis of randomized controlled trials

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Geng H

2017-03-01

Full Text Available Hua Geng, Chengzhong Wang Department of Pediatrics, Maternal and Child Health Hospital of Yancheng, Yancheng City, People’s Republic of China Background: To assess the efficacy and safety of oxcarbazepine (OXC in the treatment of children with epilepsy.Methods: Randomized controlled trials (RCTs published in PubMed, Embase, Web of Science, Cochrane Library, Scopus, SinoMed (Chinese BioMedical Literature Service System, China, and Chinese National Knowledge Infrastructure (China database were systematically reviewed. Eligible studies were those that compared the efficacy and safety of OXC with other antiepileptic drugs in epilepsy. Risk ratio (RR with 95% confidence intervals (95% CIs was calculated using fixed-effects or random-effects model.Results: Eleven RCTs with a total of 1,241 patients met the inclusion criteria and were included in this meta-analysis. Compared with other antiepileptic drugs (sodium valproate, levetiracetam, phenytoin, and placebo, OXC was associated with similar seizure-free rate (RR =1.06, 95% CI: 0.94, 1.20; P=0.366 and percentage reduction from baseline in seizure frequency (for ≥75% reduction: RR =1.15, 95% CI: 0.88, 1.49; P=0.310; for 50%–75% reduction: RR =1.12, 95% CI: 0.90, 1.39; P=0.301; for <50% reduction: RR =0.79, 95% CI: 0.56, 1.12; P=0.179. Moreover, patients treated with OXC had a comparable incidence of adverse events compared with those treated with other antiepileptic drugs (RR =1.01, 95% CI: 0.92, 1.11; P=0.760.Conclusion: OXC showed similar effects and safety as other antiepileptic drugs in the treatment of children with epilepsy. Further well-conducted, large-scale RCTs are needed to validate these findings. Keywords: epilepsy, children, oxcarbazepine, meta-analysis

When referring physicians and researchers disagree on equipoise : the TOTAL trial experience

NARCIS (Netherlands)

Rodrigues, H. C. M. L.; Deprest, J.; v. d. Berg, P. P.

Objective In this article, we reflect on whether randomized controlled trials (RCTs) are adequate for the clinical evaluation of maternal-fetal surgery for congenital diaphragmatic hernia (CDH), focusing on the role of patients' preferences in the setting up of research protocols, on the requirement

A systematic review of the quality of randomized controlled trials in head and neck oncology surgery.

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Carlton, Daniel A; Kocherginsky, Masha; Langerman, Alexander J

2015-01-01

To determine the quality of randomized controlled trials (RCTs) in head and neck surgery in which surgery was a primary intervention. Potential articles were identified in PubMed without publication date restrictions. Articles were scored using the CONSORT checklist and the relationship between the checklist score and whether the first and/or last authors were surgeons was investigated. Differences in the checklist score based on how many surgeons were among the first and last authors of the study were analyzed using the Kruskal-Wallis test. Fisher's exact test was used to examine if there was a significant difference of the reporting of individual items from the checklist between surgeons and nonsurgeons. A nonparametric trend test was used to determine whether there was a difference in the reporting of individual items based on whether there were none, one, or two surgeons among first and last authors. A total of 38 publications satisfied the inclusion criteria. There was a trend toward lower quality for studies in which surgeons were either first, last, or both first and last authors compared to studies that were first-authored and last-authored by nonsurgeons (P = 0.068). Nonsurgeons were more likely to report on critical elements regarding hypothesis, sample size determination, randomization, and eligibility of centers (P = 0.023-0.058). The quality of RCTs in head and neck surgery is poor. Improved training in conducting and reporting clinical research is needed in otolaryngology residencies. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Can smartphone mental health interventions reduce symptoms of anxiety? A meta-analysis of randomized controlled trials.

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Firth, Joseph; Torous, John; Nicholas, Jennifer; Carney, Rebekah; Rosenbaum, Simon; Sarris, Jerome

2017-08-15

Various psychological interventions are effective for reducing symptoms of anxiety when used alone, or as an adjunct to anti-anxiety medications. Recent studies have further indicated that smartphone-supported psychological interventions may also reduce anxiety, although the role of mobile devices in the treatment and management of anxiety disorders has yet to be established. We conducted a systematic review and meta-analysis of all randomized clinical trials (RCTs) reporting the effects of psychological interventions delivered via smartphone on symptoms of anxiety (sub-clinical or diagnosed anxiety disorders). A systematic search of major electronic databases conducted in November 2016 identified 9 eligible RCTs, with 1837 participants. Random-effects meta-analyses were used to calculate the standardized mean difference (as Hedges' g) between smartphone interventions and control conditions. Significantly greater reductions in total anxiety scores were observed from smartphone interventions than control conditions (g=0.325, 95% C.I.=0.17-0.48, psmartphone interventions were significantly greater when compared to waitlist/inactive controls (g=0.45, 95% C.I.=0.30-0.61, psmartphone interventions can match (or exceed) the efficacy of recognised treatments for anxiety has yet to established. This meta-analysis shows that psychological interventions delivered via smartphone devices can reduce anxiety. Future research should aim to develop pragmatic methods for implementing smartphone-based support for people with anxiety, while also comparing the efficacy of these interventions to standard face-to-face psychological care. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

[Adequate application of quantitative and qualitative statistic analytic methods in acupuncture clinical trials].

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Tan, Ming T; Liu, Jian-ping; Lao, Lixing

2012-08-01

Recently, proper use of the statistical methods in traditional Chinese medicine (TCM) randomized controlled trials (RCTs) has received increased attention. Statistical inference based on hypothesis testing is the foundation of clinical trials and evidence-based medicine. In this article, the authors described the methodological differences between literature published in Chinese and Western journals in the design and analysis of acupuncture RCTs and the application of basic statistical principles. In China, qualitative analysis method has been widely used in acupuncture and TCM clinical trials, while the between-group quantitative analysis methods on clinical symptom scores are commonly used in the West. The evidence for and against these analytical differences were discussed based on the data of RCTs assessing acupuncture for pain relief. The authors concluded that although both methods have their unique advantages, quantitative analysis should be used as the primary analysis while qualitative analysis can be a secondary criterion for analysis. The purpose of this paper is to inspire further discussion of such special issues in clinical research design and thus contribute to the increased scientific rigor of TCM research.

The efficacy and safety of 10 mg vortioxetine in the treatment of major depressive disorder: a meta-analysis of randomized controlled trials

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Li G

2016-02-01

Full Text Available Guangjian Li, Xu Wang, Dihui Ma Department of Neurology and Neuroscience Center, First Hospital of Jilin University, Changchun, People’s Republic of China Background: Vortioxetine is an investigational multimodal antidepressant. We conducted this meta-analysis to assess the efficacy and safety of 10 mg vortioxetine in the treatment of major depressive disorder (MDD. Methods: Randomized controlled trials (RCTs published in PubMed, Web of Science, Embase, and ClinicalTrials.gov were systematically reviewed to assess the treatment effects and safety profiles of patients with MDD who were treated with 10 mg vortioxetine. The outcome measures included response rate, remission rate, changes from baseline in Montgomery–Asberg Depression Rating Scale (MADRS, Hamilton Rating Scale for Depression (24-items (HAM-D24, Clinical Global Impression-Severity (CGI-S, and Clinical Global Impression-Improvement (CGI-I scores. Results were expressed with risk ratio or weighted mean difference with 95% confidence intervals. Pooled results were calculated using a fixed-effects model or a random-effects model according to the heterogeneity among included trials. Results: Six RCTs with a total of 1,801 patients met the inclusion criteria and were included in this meta-analysis. The 10 mg vortioxetine dose significantly increased the response rate and remission rate in the treatment of MDD compared with placebo. Moreover, there was a statistically significant reduction from baseline in the MADRS, HAM-D24, CGI-S, and CGI-I scores with 10 mg vortioxetine vs placebo. The incidence of treatment-emergent adverse events such as nausea, vomiting, constipation, and hyperhidrosis was higher in the 10 mg vortioxetine group than in the placebo group. Conclusion: Vortioxetine 10 mg can significantly increase the response rate and remission rate, and reduce the MADRS, HAM-D24, CGI-S, and CGI-I scores in patients with MDD with an acceptable risk of treatment-emergent adverse

Methodological characteristics and treatment effect sizes in oral health randomised controlled trials: Is there a relationship? Protocol for a meta-epidemiological study.

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Saltaji, Humam; Armijo-Olivo, Susan; Cummings, Greta G; Amin, Maryam; Flores-Mir, Carlos

2014-02-25

It is fundamental that randomised controlled trials (RCTs) are properly conducted in order to reach well-supported conclusions. However, there is emerging evidence that RCTs are subject to biases which can overestimate or underestimate the true treatment effect, due to flaws in the study design characteristics of such trials. The extent to which this holds true in oral health RCTs, which have some unique design characteristics compared to RCTs in other health fields, is unclear. As such, we aim to examine the empirical evidence quantifying the extent of bias associated with methodological and non-methodological characteristics in oral health RCTs. We plan to perform a meta-epidemiological study, where a sample size of 60 meta-analyses (MAs) including approximately 600 RCTs will be selected. The MAs will be randomly obtained from the Oral Health Database of Systematic Reviews using a random number table; and will be considered for inclusion if they include a minimum of five RCTs, and examine a therapeutic intervention related to one of the recognised dental specialties. RCTs identified in selected MAs will be subsequently included if their study design includes a comparison between an intervention group and a placebo group or another intervention group. Data will be extracted from selected trials included in MAs based on a number of methodological and non-methodological characteristics. Moreover, the risk of bias will be assessed using the Cochrane Risk of Bias tool. Effect size estimates and measures of variability for the main outcome will be extracted from each RCT included in selected MAs, and a two-level analysis will be conducted using a meta-meta-analytic approach with a random effects model to allow for intra-MA and inter-MA heterogeneity. The intended audiences of the findings will include dental clinicians, oral health researchers, policymakers and graduate students. The aforementioned will be introduced to the findings through workshops, seminars, round

The clinically-integrated randomized trial: proposed novel method for conducting large trials at low cost

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Scardino Peter T

2009-03-01

Full Text Available Abstract Introduction Randomized controlled trials provide the best method of determining which of two comparable treatments is preferable. Unfortunately, contemporary randomized trials have become increasingly expensive, complex and burdened by regulation, so much so that many trials are of doubtful feasibility. Discussion Here we present a proposal for a novel, streamlined approach to randomized trials: the "clinically-integrated randomized trial". The key aspect of our methodology is that the clinical experience of the patient and doctor is virtually indistinguishable whether or not the patient is randomized, primarily because outcome data are obtained from routine clinical data, or from short, web-based questionnaires. Integration of a randomized trial into routine clinical practice also implies that there should be an attempt to randomize every patient, a corollary of which is that eligibility criteria are minimized. The similar clinical experience of patients on- and off-study also entails that the marginal cost of putting an additional patient on trial is negligible. We propose examples of how the clinically-integrated randomized trial might be applied in four distinct areas of medicine: comparisons of surgical techniques, "me too" drugs, rare diseases and lifestyle interventions. Barriers to implementing clinically-integrated randomized trials are discussed. Conclusion The proposed clinically-integrated randomized trial may allow us to enlarge dramatically the number of clinical questions that can be addressed by randomization.

Randomized Clinical Trial of Parent-Focused Treatment and Family-Based Treatment for Adolescent Anorexia Nervosa.

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Le Grange, Daniel; Hughes, Elizabeth K; Court, Andrew; Yeo, Michele; Crosby, Ross D; Sawyer, Susan M

2016-08-01

There have been few randomized clinical trials (RCTs) for adolescents with anorexia nervosa (AN). Most of these posit that involving all family members in treatment supports favorable outcomes. However, at least 2 RCTs suggest that separate parent and adolescent sessions may be just as effective as conjoint treatment. This study compared the relative efficacy of family-based treatment (FBT) and parent-focused treatment (PFT). In PFT, the therapist meets with the parents only, while a nurse monitors the patient. Participants (N = 107) aged 12 to 18 years and meeting DSM 4(th)Edition criteria for AN or partial AN were randomized to either FBT or PFT. Participants were assessed at baseline, end of treatment (EOT), and at 6 and 12 months posttreatment. Treatments comprised 18 outpatient sessions over 6 months. The primary outcome was remission, defined as ≥95% of median body mass index and Eating Disorder Examination Global Score within 1 SD of community norms. Remission was higher in PFT than in FBT at EOT (43% versus 22%; p = .016, odds ratio [OR] = 3.03, 95% CI = 1.23-7.46), but did not differ statistically at 6-month (PFT 39% versus FBT 22%; p = .053, OR = 2.48, CI = 0.989-6.22), or 12-month (PFT 37% versus FBT 29%; p = .444, OR = 1.39, 95% CI = 0.60-3.21) follow-up. Several treatment effect moderators of primary outcome were identified. At EOT, PFT was more efficacious than FBT in bringing about remission in adolescents with AN. However, differences in remission rates between PFT and FBT at follow-up were not statistically significant. A Randomised Controlled Trial of Two Forms of Family-Based Treatment and the Effect on Percent Ideal Body Weight and Eating Disorders Symptoms in Adolescent Anorexia Nervosa; http://www.anzctr.org.au/; ACTRN12610000216011. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials.

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Yunhui Zeng

Full Text Available To evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI.PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL, Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP were searched for randomized controlled trials (RCTs comparing progesterone and placebo administrated in acute TBI patients. The primary outcome was mortality and the secondary outcomes were unfavorable outcomes and adverse events. A meta-analysis was conducted to evaluate the efficacy and safety of progesterone administrated in patients with acute TBI.A total of 6 studies met inclusion criteria, involving 2,476 patients. The risk of bias was considered to be low in 4 studies but high in the other 2 studies. The results of meta-analysis indicated progesterone did not reduce the mortality (RR = 0.83, 95% CI = 0.57-1.20 or unfavorable outcomes (RR = 0.89, 95% CI = 0.78-1.02 of acute TBI patients in comparison with placebo. Sensitivity analysis yielded consistent results. Progesterone was basically safe and well tolerated in TBI patients with the exception of increased risk of phlebitis or thrombophlebitis (RR = 3.03, 95% CI = 1.96-4.66.Despite some modest bias, present evidence demonstrated that progesterone was well tolerated but did not reduce the mortality or unfavorable outcomes of adult patients with acute TBI.

Systematic review on randomized controlled trials of coronary heart disease complicated with depression treated with Chinese herbal medicines.

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Wang, An-Lu; Chen, Zhuo; Luo, Jing; Shang, Qing-Hua; Xu, Hao

2016-01-01

This systemic review evaluated the efficacy and safety of Chinese herbal medicines (CHMs) in patients with coronary heart disease (CHD) complicated with depression. All databases were retrieved till September 30, 2014. Randomized controlled trials (RCTs) comparing CHMs with placebo or conventional Western medicine were retrieved. Data extraction, analyses and quality assessment were performed according to the Cochrane standards. RevMan 5.3 was used to synthesize the results. Thirteen RCTs enrolling 1,095 patients were included. Subgroup analysis was used to assess data. In reducing the degree of depression, CHMs showed no statistic difference in the 4th week [mean difference (MD)=-1.06; 95% confidence interval (CI)-2.38 to 0.26; n=501; I(2)=73%], but it was associated with a statistically significant difference in the 8th week (MD=-1.00; 95% CI-1.64 to-0.36; n=436; I(2)=48%). Meanwhile, the combination therapy (CHMs together with antidepressants) showed significant statistic differences both in the 4th week (MD=-1.99; 95% CI-3.80 to-0.18; n=90) and in the 8th week (MD=-5.61; 95% CI-6.26 to-4.97; n=242; I(2)=87%). In CHD-related clinical evaluation, 3 trials reported the intervention group was superior to the control group. Four trials showed adverse events in the intervention group was less than that in the control group. CHMs showed potentially benefits on patients with CHD complicated with depression. Moreover, the effect of CHMs may be similar to or better than antidepressant in certain fields but with less side effects. However, because of small sample size and potential bias of most trials, this result should be interpreted with caution. More rigorous trials with larger sample size and higher quality are warranted to give high quality of evidence to support the use of CHMs for CHD complicated with depression.

Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials

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Vittorio Unfer1,

2017-10-01

Full Text Available Myo-inositol (MI supplementation in women with polycystic ovary syndrome (PCOS has been evaluated over the last years. Many hormonal and reproductive impairments associated with this disorder seem relieved by the supplement. The objective of the meta-analysis was to assess the effects of MI alone or combined with d-chiro-inositol (DCI on the endocrine and metabolic abnormalities of women with PCOS. Literature was retrieved from selected databases, MEDLINE, EMBASE, PubMed and Research Gate (up to November 2016. Only randomized controlled trials (RCTs investigating the effects of MI alone or combined with DdCI were reviewed. Nine RCTs involving 247 cases and 249 controls were included. Significant decreases in fasting insulin (SMD = −1.021 μU/mL, 95% CI: −1.791 to −0.251, P = 0.009 and homeostasis model assessment (HOMA index (SMD = −0.585, 95% CI: −1.145 to −0.025, P = 0.041 were identified after MI supplementation. The trial sequential analysis of insulin meta-analysis illustrates that the cumulative z-curve crossed the monitoring boundary, providing firm evidence of the intervention effect. A slight trend toward a reduction of testosterone concentration by MI with respect to controls was found (SMD = −0.49, 95% CI: −1.072 to 0.092, P = 0.099, whereas androstenedione levels remained unaffected. Throughout a subgroup’s meta-analysis, a significant increase in serum SHBG was observed only in those studies where MI was administered for at least 24 weeks (SMD = 0.425 nmol/L, 95% CI: 0.050–0.801, P = 0.026. These results highlight the beneficial effect of MI in improving the metabolic profile of women with PCOS, concomitantly reducing their hyperandrogenism.

Effectiveness of aquatic exercise and balneotherapy: a summary of systematic reviews based on randomized controlled trials of water immersion therapies.

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Kamioka, Hiroharu; Tsutani, Kiichiro; Okuizumi, Hiroyasu; Mutoh, Yoshiteru; Ohta, Miho; Handa, Shuichi; Okada, Shinpei; Kitayuguchi, Jun; Kamada, Masamitsu; Shiozawa, Nobuyoshi; Honda, Takuya

2010-01-01

The objective of this review was to summarize findings on aquatic exercise and balneotherapy and to assess the quality of systematic reviews based on randomized controlled trials. Studies were eligible if they were systematic reviews based on randomized clinical trials (with or without a meta-analysis) that included at least 1 treatment group that received aquatic exercise or balneotherapy. We searched the following databases: Cochrane Database Systematic Review, MEDLINE, CINAHL, Web of Science, JDream II, and Ichushi-Web for articles published from the year 1990 to August 17, 2008. We found evidence that aquatic exercise had small but statistically significant effects on pain relief and related outcome measures of locomotor diseases (eg, arthritis, rheumatoid diseases, and low back pain). However, long-term effectiveness was unclear. Because evidence was lacking due to the poor methodological quality of balneotherapy studies, we were unable to make any conclusions on the effects of intervention. There were frequent flaws regarding the description of excluded RCTs and the assessment of publication bias in several trials. Two of the present authors independently assessed the quality of articles using the AMSTAR checklist. Aquatic exercise had a small but statistically significant short-term effect on locomotor diseases. However, the effectiveness of balneotherapy in curing disease or improving health remains unclear.

Risk of fatigue in cancer patients receiving anti-EGFR monoclonal antibodies: results from a systematic review and meta-analysis of randomized controlled trial.

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Zhu, Jianhong; Zhao, Wenxia; Liang, Dan; Li, Guocheng; Qiu, Kaifeng; Wu, Junyan; Li, Jianfang

2018-04-01

To evaluate the association between fatigue and anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MAbs), we conducted the first meta-analysis to access the incidence and risk of fatigue associated with anti-EGFR MAbs. Electronic databases were searched for randomized controlled trials (RCTs) published up to February 2017. Eligible studies were selected according to PRISMA statement. Incidence rates, risk ratio (RRs), and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models. Outcomes of quality were summarized in accordance with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology. Thirty-five RCTs (including 15,622 patients) were included; median follow-up ranged from 8.1 to 71.4 months, and the fatigue events were recorded and graded according to the Common Toxicity Criteria for Adverse Events version 2.0 or 3.0 in most of the included trials. For patients receiving anti-EGFR MAbs, the overall incidence of all-grade and high-grade fatigue was 54.1% and 10.5%, respectively. Compared with control, anti-EGFR MAbs significantly increased the risk of all-grade fatigue (RR 1.10, 95% CI, 1.05-1.14, moderate-quality evidence) and high-grade fatigue (RR 1.31, 95% CI, 1.19-1.45, moderate-quality evidence). No significant differences among subgroup analyses (anti-EGFR MAbs, tumor type, and median follow-up) on high-grade fatigue were observed. No evidence of publication bias was observed. The present study suggested that anti-EGFR MAbs may increase the risk of fatigue in cancer patients.

Trial efficacy vs real world effectiveness in first line treatment of multiple myeloma

NARCIS (Netherlands)

Liwing, J.; Heeg, B.M.; Karstorp, S.; Postma, M.; Silvennoinen, R.; Putkonen, M.; Anttila, P.; Remes, K.; Abildgaard, N.; Waage, A.; Nahi, H.

2015-01-01

Background: Large randomized clinical trials (RCT) are the foundation of the registration of newly developed drugs. A potential problem with RCTs is that the inclusion/exclusion criteria will make the population different from the actual population treated in real life. Hence, it is important to

Efficacy, acceptability and safety of guided imagery/hypnosis in fibromyalgia - A systematic review and meta-analysis of randomized controlled trials.

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Zech, N; Hansen, E; Bernardy, K; Häuser, W

2017-02-01

This systematic review aimed at evaluating the efficacy, acceptability and safety of guided imagery/hypnosis (GI/H) in fibromyalgia. Cochrane Library, MEDLINE, PsycINFO and SCOPUS were screened through February 2016. Randomized controlled trials (RCTs) comparing GI/H with controls were analysed. Primary outcomes were ≥50% pain relief, ≥20% improvement of health-related quality of life, psychological distress, disability, acceptability and safety at end of therapy and 3-month follow-up. Effects were summarized by a random effects model using risk differences (RD) or standardized mean differences (SMD) with 95% confidence intervals (CI).Seven RCTs with 387 subjects were included into a comparison of GI/H versus controls. There was a clinically relevant benefit of GI/H compared to controls on ≥50% pain relief [RD 0.18 (95% CI 0.02, 0.35)] and psychological distress [SMD -0.40 (95% CI -0.70, -0.11)] at the end of therapy. Acceptability at the end of treatment for GI/H was not significantly different to the control. Two RCTs with 95 subjects were included in the comparison of hypnosis combined with cognitive behavioural therapy (CBT) versus CBT alone. Combined therapy was superior to CBT alone in reducing psychological distress at the end of therapy [SMD -0.50 (95% CI -0.91, -0.09)]. There were no statistically significant differences between combined therapy and CBT alone in other primary outcomes at the end of treatment and follow-up. No study reported on safety. GI/H hold promise in a multicomponent management of fibromyalgia. We provide a systematic review with meta-analysis on guided imagery and hypnosis for fibromyalgia. Current analyses endorse the efficacy and tolerability of guided imagery/hypnosis and of the combination of hypnosis with cognitive-behavioural therapy in reducing key symptoms of fibromyalgia. © 2016 European Pain Federation - EFIC®.

Influence of tranexamic acid on cerebral hemorrhage: A meta-analysis of randomized controlled trials.

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Huang, Beilei; Xu, Qiusheng; Ye, Ru; Xu, Jun

2018-06-12

Tranexamic acid might be beneficial for cerebral hemorrhage. However, the results remained controversial. We conducted a systematic review and meta-analysis to explore the influence of tranexamic acid on cerebral hemorrhage. PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of tranexamic acid on cerebral hemorrhage were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. This meta-analysis was performed using the random-effect model. Seven RCTs involving 1702 patients were included in the meta-analysis. Overall, compared with control intervention in cerebral hemorrhage, tranexamic acid could significantly reduce growth of hemorrhagic mass (RR = 0.78; 95% CI = 0.61-0.99; P = 0.04) and unfavorable outcome (RR = 0.75; 95% CI = 0.61-0.93; P = 0.008), but demonstrated no substantial influence on volume of hemorrhagic lesion (Std. MD = -0.10; 95% CI = -0.27 to 0.08; P = 0.28), neurologic deterioration (RR = 1.25; 95% CI = 0.60-2.60; P = 0.56), rebleeding (RR = 0.62; 95% CI = 0.35-1.09; P = 0.10), surgery requirement (RR = 0.78; 95% CI = 0.40-1.51; P = 0.46), and mortality (RR = 0.86; 95% CI = 0.69-1.05; P = 0.14). Compared to control intervention in cerebral hemorrhage, tranexamic acid was found to significantly decrease growth of hemorrhagic mass and unfavorable outcome, but showed no notable impact on volume of hemorrhagic lesion, neurologic deterioration, rebleeding, surgery requirement and mortality. Copyright © 2018 Elsevier B.V. All rights reserved.

Opioid analgesics-related pharmacokinetic drug interactions: from the perspectives of evidence based on randomized controlled trials and clinical risk management

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Feng XQ

2017-05-01

Full Text Available Xiu-qin Feng,1 Ling-ling Zhu,2 Quan Zhou3 1Nursing Administration Office, Division of Nursing, 2VIP Care Ward, Division of Nursing, 3Department of Pharmacy, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China Background: Multimorbidity results in complex polypharmacy which may bear a risk of drug interactions. A better understanding of opioid analgesics combination therapy used for pain management could help warrant medication safety, efficacy, and economic relevance. Until now there has been no review summarizing the opioid analgesics-related pharmacokinetic drug interactions from the perspective of evidence based on randomized controlled trials (RCTs. Method: A literature search was performed using PubMed, MEDLINE, and the Cochrane Library, using a PRISMA flowchart. Results: Fifty-two RCTs were included for data interpretation. Forty-two RCTs (80.8% were conducted in healthy volunteers, whereas 10 RCTs (19.2% enrolled true patients. None of the opioid–drug/herb pairs was listed as contraindications of opioids involved in this review. Circumstances in which opioid is comedicated as a precipitant drug include morphine–P2Y12 inhibitors, morphine–gabapentin, and methadone–zidovudine. Circumstances in which opioid is comedicated as an object drug include rifampin–opioids (morphine, tramadol, oxycodone, methadone, quinidine–opioids (morphine, fentanyl, oxycodone, codeine, dihydrocodeine, methadone, antimycotics–opioids (buprenorphine, fentanyl, morphine, oxycodone, methadone, tilidine, tramadol, protease inhibitors–opioids (ritonavir, ritonavir/lopinavir–oxycodone, ritonavir–fentanyl, ritonavir–tilidine, grapefruit juice–opioids (oxycodone, fentanyl, methadone, antidepressants–opioids (paroxetine–tramadol, paroxetine–hydrocodone, paroxetine–oxycodone, escitalopram–tramadol, metoclopramide–morphine, amantadine–morphine, sumatriptan�

Effects of chemopreventive agents on the incidence of recurrent colorectal adenomas: a systematic review with network meta-analysis of randomized controlled trials

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Veettil SK

2017-05-01

Full Text Available Sajesh K Veettil,1 Nattawat Teerawattanapong,2 Siew Mooi Ching,3,4 Kean Ghee Lim,5 Surasak Saokaew,6–9 Pochamana Phisalprapa,10 Nathorn Chaiyakunapruk7,8,11,12 1School of Pharmacy/School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia; 2Division of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand; 3Department of Family Medicine, Faculty of Medicine and Health Sciences, 4Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, 5Clinical School, Department of Surgery, International Medical University, Seremban, Negeri Sembilan, 6Center of Health Outcomes Research and Therapeutic Safety (Cohorts, School of Pharmaceutical Sciences, University of Phayao, Phayao, 7School of Pharmacy, Monash University Malaysia, Selangor, Malaysia; 8Centre of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 9Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao, Thailand; 10Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 11School of Pharmacy, University of Wisconsin, Madison, USA; 12Health and Well-being Cluster, Global Asia Platform in the 21st Century (GA21 Platform, Monash University Malaysia, Selangor, Malaysia Background: Protective effects of several chemopreventive agents (CPAs against colorectal adenomas have been well documented in randomized controlled trials (RCTs; however, there is uncertainty regarding which agents are the most effective.Methods: We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. We performed both pairwise analysis and network meta-analysis (NMA of RCTs to compare the effects of CPAs on the recurrence of colorectal adenomas (primary outcome. Using NMA, we

Barriers towards the publication of academic drug trials. Follow-up of trials approved by the Danish Medicines Agency.

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Berendt, Louise; Petersen, Lene Grejs; Bach, Karin Friis; Poulsen, Henrik Enghusen; Dalhoff, Kim

2017-01-01

To characterize and quantify barriers towards the publication of academic drug trials. We identified academic drug trials approved during a 3-year period (2004-2007) by the Danish Medicines Agency. We conducted a survey among the trial sponsors to describe the rates of initiation, completion, and publication, and the reasons for the failure to reach each of these milestones. Information on size and methodological characteristics of the trials was extracted from the EudraCT database, a prospective register of all approved clinical drug trials submitted to European medicines agencies since 2004. A total of 181 academic drug trials were eligible for inclusion, 139 of which participated in our survey (response rate: 77%). Follow-up time ranged from 5.1 to 7.9 years. Most trials were randomized controlled trials (73%, 95% CI 65-81%). Initiation and completion rates were 92% (95% CI: 88-97%) and 93% (95% CI: 89-97%) respectively. The publication rate of completed trials was 73% (95% CI: 62-79%). RCTs were published faster than non-RCTs (quartile time to publication 2.9 vs. 3.1 years, p = 0.0412). Many academic drug trials are left unpublished. Main barriers towards publication were related to the process from completion to publication. Hence, there is much to gain by facilitating the process from analysis to publication. Research institutions and funders should actively influence this process, e.g. by requiring the publication of trial results within a given time after completion.

Reduced dietary sodium intake increases heart rate. A meta-analysis of 63 randomized controlled trials including 72 study populations.

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Niels eGraudal

2016-03-01

Full Text Available Reduced dietary sodium intake (sodium reduction increases heart rate in some studies of animals and humans. As heart rate is independently associated with the development of heart failure and increased risk of premature death a potential increase in heart rate could be a harmful side-effect of sodium reduction. The purpose of the present meta-analysis was to investigate the effect of sodium reduction on heart rate. Relevant studies were retrieved from an updated pool of 176 randomized controlled trials (RCTs published in the period 1973–2014. 63 of the RCTs including 72 study populations reported data on heart rate. In a meta-analysis of these data sodium reduction increased heart rate with 1.65 beats per minute [95% CI: 1.19, 2.11], p < 0.00001, corresponding to 2.4% of the baseline heart rate. This effect was independent of baseline blood pressure. In conclusion sodium reduction increases heart rate by as much (2.4% as it decreases blood pressure (2.5%. This side-effect, which may cause harmful health effects, contributes to the need for a revision of the present dietary guidelines.

A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.

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Hadjigeorgiou, G M; Doxani, C; Miligkos, M; Ziakas, P; Bakalos, G; Papadimitriou, D; Mprotsis, T; Grigoriadis, N; Zintzaras, E

2013-12-01

The relative effectiveness and safety profile of the treatments with marketing authorization for relapsing multiple sclerosis (MS) are not well known because randomized controlled trials with head-to-head comparisons between these treatments do not exist. Thus, a network of multiple-treatments meta-analysis was performed using four clinical outcomes: 'patients free of relapse', 'patients without disease progression', 'patients without MRI progression' and 'patients with adverse events'. Randomized controlled trials (RCTs) on MS were systematically searched in PubMed and Cochrane Central Register of Controlled Trial. The network analysis performed pairwise comparisons between the marketed treatments (Betaferon 250mcg, Avonex 30mcg, Rebif 44mcg, Rebif 22mcg, Aubagio 7 mg, Aubagio 14 mg, Copaxone 20 mg, Tysabri 300 mg, Gilenya 0·5 mg and Novantrone 12 mg/m(2)) using direct and indirect analyses. The analysis included 48 articles, involving 20 455 patients with MS. The direct analysis showed better response for more than one outcome for Gilenya compared with Avonex ('patients free of relapse' and 'patients without MRI progression') and for Betaferon compared with Avonex ('patients without disease progression' and 'patients without MRI progression'). The indirect analysis indicated that Tysabri may have better relative effectiveness compared with the other treatments for two outcomes: 'patients free of relapse' and 'patients without MRI progression'. Regarding 'patients with adverse events', no data were available for all comparisons to make fair inferences. This was an attempt, for the first time, to compare the efficacy and safety profile of existing approved treatments for relapsing MS. Although some treatments have shown better response, the results of the network analysis should be interpreted with caution because of the lack of RCTs with head-to-head comparisons between treatments. © 2013 John Wiley & Sons Ltd.

Registration status and outcome reporting of trials published in core headache medicine journals.

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Rayhill, Melissa L; Sharon, Roni; Burch, Rebecca; Loder, Elizabeth

2015-11-17

To evaluate randomized controlled trial (RCT) registration and outcome reporting compliance in core headache medicine journals. We identified RCTs published in core journals (Headache, Cephalalgia, and the Journal of Headache and Pain) from 2005 through 2014. We searched articles for trial registration numbers, which were verified in the corresponding trial registry. We categorized trial funding sources as industry, academic, government, or mixed. We contacted corresponding authors to assess reasons for nonregistration. We evaluated whether primary outcomes in trial registries matched those in corresponding publications. The journals published 225 RCTs over the study period. Fifty-eight of 225 (26%) reported a trial registration number in the article that could be linked to a corresponding registry entry. Trial registration rates increased over the 9 years of the study. Forty-six of 118 (39%) of industry-funded studies were registered compared with 27% of academic and 0% of government-funded studies. Only 5% of RCTs were prospectively registered, reported primary outcomes identical to those in the trial registry, and did not report unacknowledged post hoc outcomes. The most common reason for nonregistration was lack of awareness. Only about a quarter of the articles published in the core headache medicine journals are compliant with trial registration, but compliance has increased over time. Selective reporting of outcomes remains a problem, and very few trials met all 3 reporting standards assessed in this study. Efforts to improve the quality of trial reporting in the headache literature should continue. © 2015 American Academy of Neurology.

Effect of psychiatric consultation models in primary care. A systematic review and meta-analysis of randomized clinical trials.

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van der Feltz-Cornelis, Christina M; Van Os, Titus W D P; Van Marwijk, Harm W J; Leentjens, Albert F G

2010-06-01

Psychiatric consultation in primary care is meant to enhance and improve treatment for mental disorder in that setting. An estimate of the effect for different conditions as well as identification of particularly effective elements is needed. Database search for randomized controlled trials (RCTs) on psychiatric consultation in primary care. Validity assessment and data extraction according to Cochrane criteria were performed by independent assessors in duplicate. Meta-analysis was performed. Data were collected from 10 RCTs with a total of 3408 included patients with somatoform disorder or depressive disorder, which compared psychiatric consultation to care as usual (CAU). Meta-analysis irrespective of condition showed a weighted mean indicating a combined assessment of illness burden as outcome of psychiatric consultation, compared to CAU, of 0.313 (95% CI 0.190-0.437). The effect was especially large in somatoform disorder (0.614; 95% CI 0.206-1.022). RCTs in which after the consult, consultation advice was given by means of a consultation letter, showed a combined weighted mean effect size of 0.561 (95% CI 0.337-0.786), while studies not using such a letter showed a small effect of 0.210 (95% CI 0.102-0.319). Effects are highest on utilization of health care services with 0.507 (95% CI 0.305-0.708). Psychiatric consultation in the primary care setting is effective in patients with somatoform and depressive disorder. Largest effects are seen in reduction of utilization of health care services. Copyright 2010 Elsevier Inc. All rights reserved.

Efficacy and safety of tumor necrosis factor-α blockers for ulcerative colitis: A systematic review and meta-analysis of published randomized controlled trials

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Yun-Na Song

2015-03-01

Full Text Available To evaluate the efficacy and safety of TNF-α blockers for ulcerative colitis. A systematic search for randomized controlled trials (RCTs of TNF-α blockers for treatment of ulcerative colitis (UC were performed in PubMed, Web of Science, Embase and cochrane clinical trial. We estimated Pooled estimates of the odds ratio (OR and relevant 95% confidence interval (CI using fixed effects model or random effects model as appropriate. Heterogeneity, publication bias, and subgroup analyses were conducted. Nine randomized controlled studies met the selection criteria with a total of 2518 patients. Five studies compared Infliximab with placebo. Two studies compared Infliximab to corticosteroids. Two studies compared Adalimumab to placebo. One study compared subcutaneous golimumab to placebo. Short-term response, short-term remission, long-term remission and mucosal healing were better in the TNF-α blocker group than in the control group (p < 0.05. TNF-α blockers decreased the colectomy rate and serious adverse reactions (p < 0.05. The TNF-α blockers were superior to controls in achieving short-term clinical response/remission, long-term remission and mucosal healing and decreased the colectomy rate and serious adverse reactions.

Best practice guidance for the use of strategies to improve retention in randomized trials developed from two consensus workshops.

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Brueton, Valerie; Stenning, Sally P; Stevenson, Fiona; Tierney, Jayne; Rait, Greta

2017-08-01

To develop best practice guidance for the use of retention strategies in randomized clinical trials (RCTs). Consensus development workshops conducted at two UK Clinical Trials Units. Sixty-six statisticians, clinicians, RCT coordinators, research scientists, research assistants, and data managers associated with RCTs participated. The consensus development workshops were based on the consensus development conference method used to develop best practice for treatment of medical conditions. Workshops commenced with a presentation of the evidence for incentives, communication, questionnaire format, behavioral, case management, and methodological retention strategies identified by a Cochrane review and associated qualitative study. Three simultaneous group discussions followed focused on (1) how convinced the workshop participants were by the evidence for retention strategies, (2) barriers to the use of effective retention strategies, (3) types of RCT follow-up that retention strategies could be used for, and (4) strategies for future research. Summaries of each group discussion were fed back to the workshop. Coded content for both workshops was compared for agreement and disagreement. Agreed consensus on best practice guidance for retention was identified. Workshop participants agreed best practice guidance for the use of small financial incentives to improve response to postal questionnaires in RCTs. Use of second-class post was thought to be adequate for postal communication with RCT participants. The most relevant validated questionnaire was considered best practice for collecting RCT data. Barriers identified for the use of effective retention strategies were: the small improvements seen in questionnaire response for the addition of monetary incentives, and perceptions among trialists that some communication strategies are outdated. Furthermore, there was resistance to change existing retention practices thought to be effective. Face-to-face and electronic follow

Comparison between paricalcitol and active non-selective vitamin D receptor activator for secondary hyperparathyroidism in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials.

Science.gov (United States)

Cai, Panpan; Tang, Xiaohong; Qin, Wei; Ji, Ling; Li, Zi

2016-04-01

The goal of this systematic review is to evaluate the efficacy and safety of paricalcitol versus active non-selective vitamin D receptor activators (VDRAs) for secondary hyperparathyroidism (SHPT) management in chronic kidney disease (CKD) patients. PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), clinicaltrials.gov (inception to September 2015), and ASN Web site were searched for relevant studies. A meta-analysis of randomized controlled trials (RCTs) and quasi-RCTs that assessed the effects and adverse events of paricalcitol and active non-selective VDRA in adult CKD patients with SHPT was performed using Review Manager 5.2. A total of 10 trials involving 734 patients were identified for this review. The quality of included trials was limited, and very few trials reported all-cause mortality or cardiovascular calcification without any differences between two groups. Compared with active non-selective VDRAs, paricalcitol showed no significant difference in both PTH reduction (MD -7.78, 95% CI -28.59-13.03, P = 0.46) and the proportion of patients who achieved the target reduction of PTH (OR 1.27, 95% CI 0.87-1.85, P = 0.22). In addition, no statistical differences were found in terms of serum calcium, episodes of hypercalcemia, serum phosphorus, calcium × phosphorus products, and bone metabolism index. Current evidence is insufficient, showing paricalcitol is superior to active non-selective VDRAs in lowering PTH or reducing the burden of mineral loading. Further trials are required to prove the tissue-selective effect of paricalcitol and to overcome the limitation of current research.