Are the Subgroup Analyses in Stroke Clinical Trials Credible? – Protocol for a Systematic Review

Abstract Background: Clinicians and decision-makers are mostly interested in how the overall effect in a randomized controlled trial impact patient differently due to differential treatment effects. Subgroup analyses of randomized trials examine if the overall treatment effect is consistent among the subgroup or to identify groups that modify the intervention effects. Well defined and performed subgroup analyses led to critical policy decisions; however, inappropriately performed subgroup analyses had resulted in incorrect decisions with negative consequences. This systematic review examines the reporting quality and the subgroup analyses’ credibility in stroke clinical trials. Methods and analysis: We will extract relevant studies from PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science using three concepts in the Medical Subject Headings (MESH) heading. Two reviewers will independently screen the title, abstract, and full text of relevant studies. We will examine the risk of bias and the credibility of reported subgroup analyses using two validated instruments, i.e., Cochrane Risk-of-Bias tool for randomized trials version 2 (RoB 2) and the Instrument for assessing the Credibility of Effect Modification Analyses (ICEMAN), respectively. Random effects regression will be used to evaluate study characteristics associated with the credibility of subgroup analyses in the included studies.Expected outcomes: This research aims to review the quality of subgroup analyses’ results and reporting. The research’s results will also provide critical methodological contributions to the statistical literature of clinical trials. Ethics and dissemination: This systematic review does not require primary patient data and does not require ethical approval. The review’s results will be published in a peer-review and scientific conferences.Trial registration number: CRD42020223133

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Adverse events associated with administration of vasopressor medications through a peripheral intravenous catheter: a systematic review and meta-analysis

Critical Care ◽

10.1186/s13054-021-03553-1 ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Victoria S. Owen ◽

Brianna K. Rosgen ◽

Stephana J. Cherak ◽

Andre Ferland ◽

Henry T. Stelfox ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Controlled Trial ◽

Meta Analysis ◽

Patient Characteristics ◽

Risk Of Bias ◽

Cochrane Central Register ◽

Prevalence Studies ◽

Incidence Proportion ◽

Subgroup Analyses

Abstract Background It is unclear whether vasopressors can be safely administered through a peripheral intravenous (PIV). Systematic review and meta-analysis methodology was used to examine the incidence of local anatomic adverse events associated with PIV vasopressor administration in patients of any age cared for in any acute care environment. Methods MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of controlled trials, and the Database of Abstracts of Reviews of Effects were searched without restriction from inception to October 2019. References of included studies and related reviews, as well as relevant conference proceedings were also searched. Studies were included if they were: (1) cohort, quasi-experimental, or randomized controlled trial study design; (2) conducted in humans of any age or clinical setting; and (3) reported on local anatomic adverse events associated with PIV vasopressor administration. Risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials or the Joanna Briggs Institute checklist for prevalence studies where appropriate. Incidence estimates were pooled using random effects meta-analysis. Subgroup analyses were used to explore sources of heterogeneity. Results Twenty-three studies were included in the systematic review, of which 16 and 7 described adults and children, respectively. Meta-analysis from 11 adult studies including 16,055 patients demonstrated a pooled incidence proportion of adverse events associated with PIV vasopressor administration as 1.8% (95% CI 0.1–4.8%, I2 = 93.7%). In children, meta-analysis from four studies and 388 patients demonstrated a pooled incidence proportion of adverse events as 3.3% (95% CI 0.0–10.1%, I2 = 82.4%). Subgroup analyses did not detect any statistically significant effects associated with stratification based on differences in clinical location, risk of bias or design between studies, PIV location and size, or vasopressor type or duration. Most studies had high or some concern for risk of bias. Conclusion The incidence of adverse events associated with PIV vasopressor administration is low. Additional research is required to examine the effects of PIV location and size, vasopressor type and dose, and patient characteristics on the safety of PIV vasopressor administration.

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Intensity of Task-Specific Training for Functional Ability Post-stroke: Protocol for a Systematic Review

10.21203/rs.3.rs-21780/v2 ◽

2021 ◽

Author(s):

Rabiu Ibrahim ◽

Isa Usman Lawal ◽

Conran Joseph

Keyword(s):

Systematic Review ◽

Literature Search ◽

Risk Of Bias ◽

Controlled Trials ◽

Cochrane Central Register ◽

Specific Training ◽

Medical Subject Headings ◽

Mesh Terms ◽

Pubmed Search ◽

Evidence Database

Abstract Background This study aimed to describe and present detailed protocol of a systematic review aimed at determining available research evidence regarding the intensity, and frequency of task-specific training ( TST ) that can best result in improved motor function and mobility outcomes in both upper and lower extremities in acute, sub-acute and chronic stroke survivors. Methods Literature search strategies were developed using Medical Subject Headings (MeSH) terms and text key words related to stroke rehabilitation and the use of TST to search for relevant randomized controlled trials (RCTs). The Cochrane Central Register of Controlled Trials, MEDLINE (PubMed search engine), Excerpta Medica dataBASE (EMBASE), Physiotherapy Evidence Database (PEDro), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Google Scholar were searched for eligible articles published from inception to date. Two reviewers independently screened the titles, selected appropriate abstract/studies and extracted relevant data as yielded by the search based on the study inclusion criteria. Assessment of the study risk of bias and quality of included studies were appraised using the Cochrane’s tool for assessing risk of bias or other appropriate tools. Discussion This paper presented the description of the systematic review methods, and it is expected to guide researchers in conducting systematic review in similar fields of research. Sources of literature search terms and reviewers have been determined. Systematic review registration The study protocol has been registered with PROSPERO (130991)

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Dental Composite Restorations Repair: A Systematic Review and Meta-analysis

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i59a34322 ◽

2021 ◽

pp. 707-738

Author(s):

Abdulmohsen Al Rabiah ◽

Alamri Zahrah ◽

Tuwaym Malath ◽

Al Daghri Ebtihal ◽

Al Suhaibani Daniyah ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Prospective Cohort ◽

Randomized Clinical Trials ◽

Assessment Tool ◽

Risk Of Bias ◽

Dental Composite ◽

Controlled Trials ◽

Cochrane Central Register ◽

Bias Assessment

Background: Controversy exists in the literature regarding the most optimal repair procedure for improving the adhesion between the repair resin and the existing resin composite materials. Hence the aim of the present study was to do a systematic review and to analyze the adhesion potential of resin-based composites to similar and dissimilar composites and aimed to determine the possible dominant factors affecting the bond strength results. Materials & Methods: Randomized clinical trials (RCTs) and prospective cohort design were searched through electronic databases including MEDLINE, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials for randomized clinical trials (RCTs) until July 2020 that compared different methods of composite restoration repair and a minimum mean follow-up time of 1 year. There were no restrictions on a particular treatment indication or outcome measures. Two authors independently conducted screening, risk of bias assessment, and data extraction of eligible trials in duplicate. We applied the Cochrane risk of bias assessment tool to consider the risk of bias. Results: We identified 10 articles; two of them were RCTs, and eight prospective cohort studies. There were 530 participants, with 990 teeth, dealing with resin-based composite (RBC) restorations. The intervention of defective restorations ranged from minimal intervention to total restoration replacement. The evaluation criteria were also varied with different evaluation protocols. The low number and heterogeneity of RCTs did not allow for meta-analyses. Conclusions: Although different repair protocols are mentioned in the literature according to the included studies, an appropriate and definitive conclusion can't be drawn. However, it seems repairs versus replacements should be considered as the first line of treatment when all factors lead to repair rather than replacement. Further randomized controlled trials with high methodological quality need to be conducted in order to establish evidence-based recommendations, particularly for RBC repair.

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Short-Term Effectiveness and Safety of Biologics and Small Molecule Drugs for Moderate to Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis

Life ◽

10.3390/life11090927 ◽

2021 ◽

Vol 11 (9) ◽

pp. 927

Author(s):

José-Juan Pereyra-Rodriguez ◽

Sara Alcantara-Luna ◽

Javier Domínguez-Cruz ◽

Manuel Galán-Gutiérrez ◽

Ricardo Ruiz-Villaverde ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Atopic Dermatitis ◽

Adverse Effects ◽

Small Molecules ◽

Meta Analysis ◽

Risk Of Bias ◽

Severe Atopic Dermatitis ◽

Cochrane Central Register ◽

Number Of Patients

Background: Some Network Meta-analysis (NMA) has been published regarding atopic dermatitis (AD). These studies have considered drugs under investigation both in monotheraphy or in combination with topical corticosteroids, as well as systemic immunosuppressant therapies. The objective of this study is to evaluate the efficacy and safety of biological agents and small molecules in AD. Methods: A systematic review and NMA of biologics agents and small molecules in AD was performed. A literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for clinical trials and systematic reviews between January 2000 and 19 December 2020. Only randomized clinical trials (RCTs) were included. It was limited to English language and adult human subjects. Two networks were evaluated: monotherapy and combination with TCS. The two primary outcomes were Eczema Area and Severity Index (EASI) 75 and EASI 90 change from baseline to week 12–16, depending on source study cut-off. The Cochrane’s Risk of Bias tool 2011 update was used to analyze the risk of bias, focused on the primary objectives. Results: 30 RCTs (included in 26 publications) were included in the systematic review. Finally, 23 RCTs were included in the quantitative analysis (14 RCTs including 3582 patients in monotherapy; and 9 RCTs including 3686 patients with TCS). In monotherapy, a higher percentage of patients achieving EASI-75 was obtained with Upadacitinib 30 mg [OR: 18.90 (13.94; 25.62)] followed by Abrocitinib 200 mg [OR = 11.26 (7.02; 18.05)] and Upadacitinib 15 mg [OR: 10.89 (8.13; 14.59)]. These results were also observed in studies where the use of topical corticosteroid (TCS) was allowed (OR Upadacitinib 30 mg = 9.43; OR Abrocitinib 200 mg = 6.12; OR Upadacitinib 15 mg = 5.20). Regarding IGA, the percentage of patients achieving IGA0/1 was higher with both doses of Upadacitinib 30 mg [OR: 19.13 (13.14; 27.85)] and 15 mg [OR = 10.95 (7.52; 15.94). In studies where the use of TCS were allowed, however, the dose of Abrocitinib 200 mg [OR = 6.10 (3.94; 9.44)] showed higher efficacy than Upadacitinib 15 mg [OR = 5.47 (3.57; 8.41)]. Regarding safety, the drugs with the highest probability of presenting adverse effects were the Janus kinases (JAK) inhibitors, Upadacitinib and Abrocitinib in monotherapy and Baricitinib in combination with TCS. Discussion: Some risks of bias have been found, which must be taken into account when interpreting the results. The funnel plot shows a possible publication bias that may underestimate the efficacy of drugs. Upadacitinib and Abrocitinib are the drugs with the highest efficacy, both in monotherapy and in association with TCS. However, they were also those associated with the highest risk of adverse effects, showing monoclonal antibodies better safety profile. Limitations: We have included molecules still in the development phase as well studies completed and presented at conferences and with data available in Trialsgov® but not published yet. Several molecules’ development had included a small number of patients from 12 to 17 years of age, without being able to differentiate the results from the adult population. Other: Founding: None. PROSPERO database registration number CRD42021225793.

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Association between increased antenatal vaginal pH and preterm birth rate: a systematic review

Journal of Perinatal Medicine ◽

10.1515/jpm-2018-0097 ◽

2019 ◽

Vol 47 (2) ◽

pp. 142-151 ◽

Cited By ~ 3

Author(s):

Marina J. Weckend ◽

Loukia M. Spineli ◽

Susanne Grylka-Baeschlin ◽

Mechthild M. Gross

Keyword(s):

Systematic Review ◽

Preterm Birth ◽

Pregnant Women ◽

Controlled Trial ◽

Preterm Births ◽

Risk Of Bias ◽

Cochrane Central Register ◽

Hand Search ◽

Vaginal Ph ◽

Tract Infections

Abstract Background Worldwide, 14.9 million infants (11%) are born preterm each year. Up to 40% of preterm births (PTBs) are associated with genital tract infections. The vaginal pH can reflect changes in the vaginal milieu and, if elevated, indicates an abnormal flora or infection. Objective The aim of the study was to investigate whether an increased antenatal vaginal pH >4.5 in pre-labour pregnant women is associated with an increased PTB rate <37 completed weeks gestation. Search strategy Key databases included SCOPUS, EMBASE, MEDLINE, PsycInfo and the Cochrane Central Register of Controlled Trials, complemented by hand search, up to January 2017. Selection criteria Primary research reporting vaginal pH assessment in pre-labour pregnant women and PTB rate. Data collection and analysis Data extraction and appraisal were carried out in a pre-defined standardised manner, applying the Newcastle-Ottawa scale (NOS) and Cochrane risk of bias tool. Analysis included calculation of risk difference (RD) and narrative synthesis. It was decided to abstain from pooling of the studies due to missing information in important moderators. Main results Of 986 identified records, 30 were included in the systematic review. The risk of bias was considered mostly high (40%) or moderate (37%). Fifteen studies permitted a calculation of RD. Of these, 14 (93%) indicated a positive association between increased antenatal vaginal pH and PTB (RD range: 0.02–0.75). Conclusion An increased antenatal vaginal pH >4.5 may be associated with a higher risk for PTB. It is recommended to conduct a randomised controlled trial (RCT) to investigate the effectiveness of antenatal pH screening to prevent PTB. Tweetable abstract Pregnant women with an increased vaginal pH >4.5 may be at higher risk to experience preterm birth.

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Omega-3 polyunsaturated fatty acid supplementation for improving peripheral nerve health: protocol for a systematic review

BMJ Open ◽

10.1136/bmjopen-2017-020804 ◽

2018 ◽

Vol 8 (3) ◽

pp. e020804 ◽

Cited By ~ 1

Author(s):

Alexis Ceecee Zhang ◽

Richard J MacIsaac ◽

Leslie Roberts ◽

Jordan Kamel ◽

Jennifer P Craig ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Peripheral Nerve ◽

Risk Of Bias ◽

Published Data ◽

Controlled Trials ◽

Cochrane Central Register ◽

Omega 3 ◽

Pufa Supplementation ◽

Clinical Trials Registry

IntroductionDamage to peripheral nerves occurs in a variety of health conditions. Preserving nerve integrity, to prevent progressive nerve damage, remains a clinical challenge. Omega-3 polyunsaturated fatty acids (PUFAs) are implicated in the development and maintenance of healthy nerves and may be beneficial for promoting peripheral nerve health. The aim of this systematic review is to assess the effects of oral omega-3 PUFA supplementation on peripheral nerve integrity, including both subjective and objective measures of peripheral nerve structure and/or function.Methods and analysisA systematic review of randomised controlled trials that have evaluated the effects of omega-3 PUFA supplementation on peripheral nerve assessments will be conducted. Comprehensive electronic database searches will be performed in Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), US National Institutes of Health Clinical Trials Registry and the WHO International Clinical Trials Registry Platform. The title, abstract and keywords of identified articles will be assessed for eligibility by two reviewers. Full-text articles will be obtained for all studies judged as eligible or potentially eligible; these studies will be independently assessed by two reviewers to determine eligibility. Disagreements will be resolved by consensus. Risk of bias assessment will be performed using the Cochrane Collaboration risk of bias tool to appraise the quality of included studies. If clinically meaningful, and there are a sufficient number of eligible studies, a meta-analysis will be conducted and a summary of findings table will be provided.Ethics and disseminationThis is a systematic review that will involve the analysis of previously published data, and therefore ethics approval is not required. A manuscript reporting the results of this systematic review will be published in a peer-reviewed journal and may also be presented at relevant scientific conferences.PROSPERO registration numberCRD42018086297.

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Improving peer review of systematic reviews by involving librarians and information specialists: protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-021-05738-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Melissa L. Rethlefsen ◽

Sara Schroter ◽

Lex M. Bouter ◽

David Moher ◽

Ana Patricia Ayala ◽

...

Keyword(s):

Systematic Review ◽

Randomized Controlled Trial ◽

Peer Review ◽

Systematic Reviews ◽

Controlled Trial ◽

Reporting Quality ◽

Risk Of Bias ◽

Randomized Controlled ◽

Peer Reviewers

Abstract Background Problems continue to exist with the reporting quality and risk of bias in search methods and strategies in systematic reviews and related review types. Peer reviewers who are not familiar with what is required to transparently and fully report a search may not be prepared to review the search components of systematic reviews, nor may they know what is likely to introduce bias into a search. Librarians and information specialists, who have expertise in searching, may offer specialized knowledge that would help improve systematic review search reporting and lessen risk of bias, but they are underutilized as methodological peer reviewers. Methods This study will evaluate the effect of adding librarians and information specialists as methodological peer reviewers on the quality of search reporting and risk of bias in systematic review searches. The study will be a pragmatic randomized controlled trial using 150 systematic review manuscripts submitted to BMJ and BMJ Open as the unit of randomization. Manuscripts that report on completed systematic reviews and related review types and have been sent for peer review are eligible. For each manuscript randomized to the intervention, a librarian/information specialist will be invited as an additional peer reviewer using standard practices for each journal. First revision manuscripts will be assessed in duplicate for reporting quality and risk of bias, using adherence to 4 items from PRISMA-S and assessors’ judgements on 4 signaling questions from ROBIS Domain 2, respectively. Identifying information from the manuscripts will be removed prior to assessment. Discussion The primary outcomes for this study are quality of reporting as indicated by differences in the proportion of adequately reported searches in first revision manuscripts between intervention and control groups and risk of bias as indicated by differences in the proportions of first revision manuscripts with high, low, and unclear bias. If the intervention demonstrates an effect on search reporting or bias, this may indicate a need for journal editors to work with librarians and information specialists as methodological peer reviewers. Trial registration Open Science Framework. Registered on June 17, 2021, at 10.17605/OSF.IO/W4CK2.

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Acupuncture for biliary colic: a systematic review protocol

BMJ Open ◽

10.1136/bmjopen-2020-041931 ◽

2021 ◽

Vol 11 (1) ◽

pp. e041931

Author(s):

Ning Sun ◽

Wenwei Zuo ◽

Yuanfang Zhou ◽

Ying Cheng ◽

Shirui Cheng ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Data Extraction ◽

Meta Analysis ◽

Risk Of Bias ◽

Biomedical Literature ◽

Biliary Colic ◽

Common Symptom ◽

Cochrane Central Register ◽

China National Knowledge Infrastructure

IntroductionBiliary colic (BC) is a severe pain associated with nausea and vomiting, which is the most common symptom among the gallstone population. This protocol proposes a methodology for conducting a systematic review and meta-analysis that aims to assess the benefits and safety of acupuncture in patients with BC.Methods and analysisClinical trials will be identified through nine databases from inception to December 2020, using Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Allied and Complementary Medicine Database (AMED), CINAHL, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP Database and Wanfang Database. Search words will be used for the BC and acupuncture. The analysis would include randomised, controlled, clinical trials of adults with BC that were published in either Chinese or English. The primary outcome is to measure pain relief. Two or three reviewers should be in charge of study selection, data extraction and evaluating the risk of bias. RevMan software (V.5.4) will be used to perform the assessment of the risk of bias and data synthesis.Ethics and disseminationEthics approval will not be required for this review, as it will only involve the collection of literature previously published. The results of this meta-analysis will be disseminated in a peer-reviewed journal or relevant conference, through publication.Trial registration numberCRD42020167510.

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Nutraceuticals and nutritional supplements for the treatment of bipolar disorder: protocol for a systematic review

BMJ Open ◽

10.1136/bmjopen-2018-025640 ◽

2019 ◽

Vol 9 (4) ◽

pp. e025640 ◽

Cited By ~ 3

Author(s):

Melanie M Ashton ◽

Michael Berk ◽

Chee H Ng ◽

Malcolm Hopwood ◽

Bianca Kavanagh ◽

...

Keyword(s):

Systematic Review ◽

Bipolar Disorder ◽

Clinical Trials ◽

Research Question ◽

Risk Of Bias ◽

Published Data ◽

Cochrane Central Register ◽

Controlled Clinical Trials ◽

Double Blind ◽

Search Terms

IntroductionFirst line pharmacological treatments for bipolar disorder (BD) can leave shortfalls in recovery leading to patients seeking alternative and adjunctive treatments such as nutraceuticals. This protocol for a systematic review and proposed meta-analysis aims to answer the research question: in patients with BD, how does use of nutraceutical treatments compare with placebo in reducing depressive and mania symptoms?Methods and analysisClinical trials will be identified through database searches using PubMed via PubMed, EMBASE via embase.com, Cochrane Central Register of Controlled Clinical Trials (CENTRAL) via cochranelibrary.com and CINAHL Complete via EBSCO. Search terms for BD and specific nutraceuticals (75 total search terms) will be used. Double-blind, randomised, controlled, clinical trials of adults with BD will be included in the review. Risk of bias will be assessed using the Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.Ethics and disseminationThis review will only look at published data (already reviewed for ethical compliance); therefore, ethical approval is not required. We aim to publish the systematic review in a peer-reviewed journal and present at conferences.PROSPERO registration numberCRD42019100745.

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Intensity of Task Specific Training for Functional ability Post-stroke: Protocol for a Systematic Review

10.21203/rs.3.rs-21780/v1 ◽

2020 ◽

Author(s):

Rabiu Ibrahim ◽

Isa Usman Lawal ◽

Conran Joseph

Keyword(s):

Systematic Review ◽

Literature Search ◽

Risk Of Bias ◽

Cochrane Central Register ◽

Specific Training ◽

Medical Subject Headings ◽

Mesh Terms ◽

Upper And Lower Extremities ◽

Pubmed Search ◽

Evidence Database

Abstract Background To describe and present detailed protocol of a systematic review aimed at determining available research evidence regarding the intensity, and frequency of Task-Specific Training that can best result in improved motor function, and mobility outcomes in both upper and lower extremities in acute, sub-acute and chronic stroke survivors. Methods Literature search strategies will be developed using Medical Subject Headings (MeSH) terms and text key words related to stroke rehabilitation and the use of TST to search for relevant RCTs. Cochrane Central Register of Controlled Trials, MEDLINE (PubMed search engine), Excerpta Medica dataBASE (EMBASE), Physiotherapy Evidence Database (PEDro), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Google Scholar will be searched for eligible articles published from inception to date. Two reviewers will independently screen the titles, select appropriate abstract/studies and extract relevant data as yielded by the search base on the study inclusion criteria. Assessment of the study risk of bias and quality of included studies will be appraised using the Cochrane’s tool for assessing risk of bias or other appropriate tool. Discussion This paper presented the description of the systematic review methods, and it is expected to guide researchers in conducting systematic review in similar field of research. Sources of literature search terms and reviewers have been determined. Systematic review registration The study protocol has been registered with PROSPERO (130991)

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