Reporting completeness of nutrition and diet-related randomised controlled trials protocols.

BACKGROUND AND AIMS: There is a need to consolidate reporting guidance for nutrition randomised controlled trial (RCT) protocols. The reporting completeness in nutrition RCT protocols and study characteristics associated with adherence to SPIRIT and TIDieR reporting guidelines are unknown. We, therefore, assessed reporting completeness and its potential predictors in a random sample of published nutrition and diet-related RCT protocols. METHODS: We conducted a meta-research study of 200 nutrition and diet-related RCT protocols published in 2019 and 2021 (aiming to consider periods before and after the start of the COVID pandemic). Data extraction included bibliometric information, general study characteristics, compliance with 122 questions corresponding to items and subitems in the SPIRIT and TIDieR checklists combined, and mention to these reporting guidelines in the publications. We calculated the proportion of protocols reporting each item and the frequency of items reported for each protocol. We investigated associations between selected publication aspects and reporting completeness using linear regression analysis. RESULTS: The majority of protocols included adults and elderly as their study population (n = 73; 36.5%), supplementation as intervention (n = 96; 48.0%), placebo as comparator (n = 89; 44.5%), and evaluated clinical status as the outcome (n = 80; 40.0%). Most protocols described a parallel RCT (n = 188; 94.0%) with a superiority framework (n = 141; 70.5%). Overall reporting completeness was 52.0% (SD = 10.8%). Adherence to SPIRIT items ranged from 0% (n = 0) (data collection methods) to 98.5% (n = 197) (eligibility criteria). Adherence to TIDieR items ranged from 5.5% (n = 11) (materials used in the intervention) to 98.5% (n = 197) (description of the intervention). The multivariable regression analysis suggests that a higher number of authors [ß = 0.53 (95%CI: 0.28-0.78)], most recent published protocols [ß = 3.19 (95%CI: 0.24-6.14)], request of reporting guideline checklist during the submission process by the journal [ß = 6.50 (95%CI: 2.56-10.43)] and mention of SPIRIT by the authors [ß = 5.15 (95%CI: 2.44-7.86)] are related to higher reporting completeness scores. CONCLUSIONS: Reporting completeness in a random sample of 200 diet or nutrition-related RCT protocols was low. Number of authors, year of publication, self-reported adherence to SPIRIT, and journals' endorsement of reporting guidelines seem to be positively associated with reporting completeness in nutrition and diet-related RCT protocols.

What do Australians affected by cancer think about oncology researchers sharing research data? A cross-sectional survey.

AIM: Previous research has shown patients and the public in Australia generally support medical researchers in making de-identified research data available to other scientists. However, this research has focussed on certain types of data and recipients. We surveyed Australians affected by cancer to characterize their attitudes toward the sharing of research data with multiple third parties, including the public. METHODS: A short, anonymous online survey of Australians with a previous diagnosis of cancer was advertised between October 27, 2022, and February 27, 2023. Quantitative responses were analyzed with descriptive statistics. Free-text responses were coded deductively and summarised using content analysis. RESULTS: In total, 551 respondents contributed data to the survey. There was strong support for cancer researchers sharing non-human and de-identified human research data with clinicians (90% and 95%, respectively) and non-profit researchers (both 94%). However, fewer participants supported sharing data with for-profit researchers (both 64%) or publicly (both 61%). When asked if they would hypothetically consent to researchers at their treatment location using and sharing their de-identified data publicly, only half agreed. In contrast, after being shown a visual representation of the de-identified survey data, 80% of respondents supported sharing it publicly. CONCLUSION: Australians affected by cancer support the sharing of research data, particularly with clinicians and non-profit researchers. Our results also imply that visualization of the data to be shared may enhance support for making it publicly available. These results should help alleviate any concerns about research participants' attitudes toward data sharing, as well as boost researchers' motivation for sharing.

Development of a search filter to retrieve reports of interrupted time series studies from MEDLINE and PubMed.

BACKGROUND: Interrupted time series (ITS) studies contribute importantly to systematic reviews of population-level interventions. We aimed to develop and validate search filters to retrieve ITS studies in MEDLINE and PubMed. METHODS: A total of 1017 known ITS studies (published 2013-2017) were analysed using text mining to generate candidate terms. A control set of 1398 time-series studies were used to select differentiating terms. Various combinations of candidate terms were iteratively tested to generate three search filters. An independent set of 700 ITS studies was used to validate the filters' sensitivities. The filters were test-run in Ovid MEDLINE and the records randomly screened for ITS studies to determine their precision. Finally, all MEDLINE filters were translated to PubMed format and their sensitivities in PubMed were estimated. RESULTS: Three search filters were created in MEDLINE: a precision-maximising filter with high precision (78%; 95% CI 74%-82%) but moderate sensitivity (63%; 59%-66%), most appropriate when there are limited resources to screen studies; a sensitivity-and-precision-maximising filter with higher sensitivity (81%; 77%-83%) but lower precision (32%; 28%-36%), providing a balance between expediency and comprehensiveness; and a sensitivity-maximising filter with high sensitivity (88%; 85%-90%) but likely very low precision, useful when combined with specific content terms. Similar sensitivity estimates were found for PubMed versions. CONCLUSION: Our filters strike different balances between comprehensiveness and screening workload and suit different research needs. Retrieval of ITS studies would be improved if authors identified the ITS design in the titles.

Identification of application and interpretation errors that can occur in pairwise meta-analyses in systematic reviews of interventions: a systematic review.

OBJECTIVES: To generate a bank of items describing application and interpretation errors that can arise in pairwise meta-analyses in systematic reviews of interventions. STUDY DESIGN AND SETTING: MEDLINE, Embase, and Scopus were searched to identify studies describing types of errors in meta-analyses. Descriptions of errors and supporting quotes were extracted by multiple authors. Errors were reviewed at team meetings to determine if they should be excluded, reworded, or combined with other errors, and were categorized into broad categories of errors and subcategories within. RESULTS: Fifty articles met our inclusion criteria, leading to the identification of 139 errors. We identified 25 errors covering data extraction/manipulation, 74 covering statistical analyses, and 40 covering interpretation. Many of the statistical analysis errors related to the meta-analysis model (eg, using a two-stage strategy to determine whether to select a fixed or random-effects model) and statistical heterogeneity (eg, not undertaking an assessment for statistical heterogeneity). CONCLUSION: We generated a comprehensive bank of possible errors that can arise in the application and interpretation of meta-analyses in systematic reviews of interventions. This item bank of errors provides the foundation for developing a checklist to help peer reviewers detect statistical errors.

Investigation of bias due to selective inclusion of study effect estimates in meta-analyses of nutrition research.

We aimed to explore, in a sample of systematic reviews (SRs) with meta-analyses of the association between food/diet and health-related outcomes, whether systematic reviewers selectively included study effect estimates in meta-analyses when multiple effect estimates were available. We randomly selected SRs of food/diet and health-related outcomes published between January 2018 and June 2019. We selected the first presented meta-analysis in each review (index meta-analysis), and extracted from study reports all study effect estimates that were eligible for inclusion in the meta-analysis. We calculated the Potential Bias Index (PBI) to quantify and test for evidence of selective inclusion. The PBI ranges from 0 to 1; values above or below 0.5 suggest selective inclusion of effect estimates more or less favourable to the intervention, respectively. We also compared the index meta-analytic estimate to the median of a randomly constructed distribution of meta-analytic estimates (i.e., the estimate expected when there is no selective inclusion). Thirty-nine SRs with 312 studies were included. The estimated PBI was 0.49 (95% CI 0.42-0.55), suggesting that the selection of study effect estimates from those reported was consistent with a process of random selection. In addition, the index meta-analytic effect estimates were similar, on average, to what we would expect to see in meta-analyses generated when there was no selective inclusion. Despite this, we recommend that systematic reviewers report the methods used to select effect estimates to include in meta-analyses, which can help readers understand the risk of selective inclusion bias in the SRs.

Cancer researchers' experiences with and perceptions of research data sharing: Results of a cross-sectional survey.

BACKGROUND: Despite wide recognition of the benefits of sharing research data, public availability rates have not increased substantially in oncology or medicine more broadly over the last decade. METHODS: We surveyed 285 cancer researchers to determine their prior experience with sharing data and views on known drivers and inhibitors. RESULTS: We found that 45% of respondents had shared some data from their most recent empirical publication, with respondents who typically studied non-human research participants, or routinely worked with human genomic data, more likely to share than those who did not. A third of respondents added that they had previously shared data privately, with 74% indicating that doing so had also led to authorship opportunities or future collaborations for them. Journal and funder policies were reported to be the biggest general drivers toward sharing, whereas commercial interests, agreements with industrial sponsors and institutional policies were the biggest prohibitors. We show that researchers' decisions about whether to share data are also likely to be influenced by participants' desires. CONCLUSIONS: Our survey suggests that increased promotion and support by research institutions, alongside greater championing of data sharing by journals and funders, may motivate more researchers in oncology to share their data.

Methods proposed for monitoring the implementation of evidence-based research: a cross-sectional study.

OBJECTIVES: Evidence-based research (EBR) is the systematic and transparent use of prior research to inform a new study so that it answers questions that matter in a valid, efficient, and accessible manner. This study surveyed experts about existing (e.g., citation analysis) and new methods for monitoring EBR and collected ideas about implementing these methods. STUDY DESIGN AND SETTING: We conducted a cross-sectional study via an online survey between November 2022 and March 2023. Participants were experts from the fields of evidence synthesis and research methodology in health research. Open-ended questions were coded by recurring themes; descriptive statistics were used for quantitative questions. RESULTS: Twenty-eight expert participants suggested that citation analysis should be supplemented with content evaluation (not just what is cited but also in which context), content expert involvement, and assessment of the quality of cited systematic reviews. They also suggested that citation analysis could be facilitated with automation tools. They emphasized that EBR monitoring should be conducted by ethics committees and funding bodies before the research starts. Challenges identified for EBR implementation monitoring were resource constraints and clarity on responsibility for EBR monitoring. CONCLUSION: Ideas proposed in this study for monitoring the implementation of EBR can be used to refine methods and define responsibility but should be further explored in terms of feasibility and acceptability. Different methods may be needed to determine if the use of EBR is improving over time.

Variation observed in consensus judgments between pairs of reviewers when assessing the risk of bias due to missing evidence in a sample of published meta-analyses of nutrition research.

OBJECTIVES: To evaluate the risk of bias due to missing evidence in a sample of published meta-analyses of nutrition research using the Risk Of Bias due to Missing Evidence (ROB-ME) tool and determine inter-rater agreement in assessments. STUDY DESIGN AND SETTING: We assembled a random sample of 42 meta-analyses of nutrition research. Eight assessors were randomly assigned to one of four pairs. Each pair assessed 21 randomly assigned meta-analyses, and each meta-analysis was assessed by two pairs. We calculated raw percentage agreement and chance corrected agreement using Gwet's Agreement Coefficient (AC) in consensus judgments between pairs. RESULTS: Across the eight signaling questions in the ROB-ME tool, raw percentage agreement ranged from 52% to 100%, and Gwet's AC ranged from 0.39 to 0.76. For the risk-of-bias judgment, the raw percentage agreement was 76% (95% confidence interval 60% to 92%) and Gwet's AC was 0.47 (95% confidence interval 0.14 to 0.80). In seven (17%) meta-analyses, either one or both pairs judged the risk of bias due to missing evidence as "low risk". CONCLUSION: Our findings indicated substantial variation in assessments in consensus judgments between pairs for the signaling questions and overall risk-of-bias judgments. More tutorials and training are needed to help researchers apply the ROB-ME tool more consistently.

The PRISMATIC project: protocol for a research programme on novel methods to improve reporting and peer review of systematic reviews of health evidence.

BACKGROUND: Incomplete reporting about what systematic reviewers did and what they found prevents users of the report from being able to fully interpret the findings and understand the limitations of the underlying evidence. Reporting guidelines such as the PRISMA statement and its extensions are designed to improve reporting. However, there are important inconsistencies across the various PRISMA reporting guidelines, which causes confusion and misinterpretation. Coupled with this, users might need to consult multiple guidelines to gain a full understanding of the guidance. Furthermore, the current passive strategy of implementing PRISMA has not fully brought about needed improvements in the completeness of systematic review reporting. METHODS: The PRISMATIC ('PRISMA, Technology, and Implementation to enhance reporting Completeness') project aims to use novel methods to enable more efficient and effective translation of PRISMA reporting guidelines into practice. We will establish a working group who will develop a unified PRISMA statement that harmonises content across the main PRISMA guideline and several of its extensions. We will then develop a web application that generates a reporting template and checklist customised to the characteristics and methods of a systematic review ('PRISMA-Web app') and conduct a randomised trial to evaluate its impact on authors' reporting. We will also develop a web application that helps peer reviewers appraise systematic review manuscripts ('PRISMA-Peer app') and conduct a diagnostic accuracy study to evaluate its impact on peer reviewers' detection of incomplete reporting. DISCUSSION: We anticipate the novel guidance and web-based apps developed throughout the project will substantively enhance the completeness of reporting of systematic reviews of health evidence, ultimately benefiting users who rely on systematic reviews to inform health care decision-making.

Efficacy of tumor necrosis factor inhibitors in hand osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.

Objectives: This study aimed at systematically review the evidence for the efficacy of Tumor Necrosis Factor (TNF) inhibitors on symptoms and structural outcomes in hand osteoarthritis. Methods: Three databases were searched for randomized controlled trials examining the efficacy of TNF inhibitors in hand osteoarthritis. Two authors extracted data and assessed the risk of bias. The mean difference (MD) was calculated, and a random-effects meta-analysis was performed. Results: Four studies were identified involving 276 participants. Meta-analysis showed that TNF inhibitors had no effect on pain at 4-6 weeks (MD -0.93, 95%CI -7.41 to 5.55; 2 studies) and 24-26 weeks (MD -3.82, 95%CI -11.46 to 3.83; 2 studies) and no effect on grip strength at 12 months (MD -0.35, 95%CI -1.08 to 0.37; 2 studies). There was limited evidence for the effect of TNF inhibitors on structural outcomes at 12 months. Subgroup analysis from 2 studies showed beneficial effect of TNF inhibitors on reducing the progression of structural outcomes in hand OA patients with signs of inflammation but not in those without inflammation. The certainty of the evidence was low for the effect of TNF inhibitor on pain and moderate for the effect on grip strength. Conclusion: This study found no effect of TNF inhibitors on clinical outcomes in hand osteoarthritis over the short term (<6 weeks) and within one year, with some evidence for beneficial effect on structural outcomes.

Prevalence and predictors of data and code sharing in the medical and health sciences: systematic review with meta-analysis of individual participant data.

OBJECTIVES: To synthesise research investigating data and code sharing in medicine and health to establish an accurate representation of the prevalence of sharing, how this frequency has changed over time, and what factors influence availability. DESIGN: Systematic review with meta-analysis of individual participant data. DATA SOURCES: Ovid Medline, Ovid Embase, and the preprint servers medRxiv, bioRxiv, and MetaArXiv were searched from inception to 1 July 2021. Forward citation searches were also performed on 30 August 2022. REVIEW METHODS: Meta-research studies that investigated data or code sharing across a sample of scientific articles presenting original medical and health research were identified. Two authors screened records, assessed the risk of bias, and extracted summary data from study reports when individual participant data could not be retrieved. Key outcomes of interest were the prevalence of statements that declared that data or code were publicly or privately available (declared availability) and the success rates of retrieving these products (actual availability). The associations between data and code availability and several factors (eg, journal policy, type of data, trial design, and human participants) were also examined. A two stage approach to meta-analysis of individual participant data was performed, with proportions and risk ratios pooled with the Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis. RESULTS: The review included 105 meta-research studies examining 2 121 580 articles across 31 specialties. Eligible studies examined a median of 195 primary articles (interquartile range 113-475), with a median publication year of 2015 (interquartile range 2012-2018). Only eight studies (8%) were classified as having a low risk of bias. Meta-analyses showed a prevalence of declared and actual public data availability of 8% (95% confidence interval 5% to 11%) and 2% (1% to 3%), respectively, between 2016 and 2021. For public code sharing, both the prevalence of declared and actual availability were estimated to be <0.5% since 2016. Meta-regressions indicated that only declared public data sharing prevalence estimates have increased over time. Compliance with mandatory data sharing policies ranged from 0% to 100% across journals and varied by type of data. In contrast, success in privately obtaining data and code from authors historically ranged between 0% and 37% and 0% and 23%, respectively. CONCLUSIONS: The review found that public code sharing was persistently low across medical research. Declarations of data sharing were also low, increasing over time, but did not always correspond to actual sharing of data. The effectiveness of mandatory data sharing policies varied substantially by journal and type of data, a finding that might be informative for policy makers when designing policies and allocating resources to audit compliance. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework doi:10.17605/OSF.IO/7SX8U.

Credibility at stake: only two-thirds of randomized trials of nutrition interventions are registered and lack transparency in outcome and treatment effect definitions.

OBJECTIVES: This study aimed to investigate the adherence of randomized controlled trials of nutrition interventions to transparency practices informing assessments of selective reporting biases, including the availability of a trial registration entry, protocol and statistical analysis plan (SAP). STUDY DESIGN AND SETTING: Retrospective observational study with cross-sectional design. We systematically searched for trials published from 1 July 2019, to 30 June 2020, and included a randomly selected sample of 400 studies. We searched for registry entries, protocols, and SAPs for all included studies. We extracted data to characterize the disclosure of sufficient information in the available materials to inform assessments of selective reporting biases, considering the definition of outcome domain, measure, metric, method of aggregation, time point, analysis population, methods to handle missing data and method of adjustment. RESULTS: Most trials (69%) were registered, but these often lacked sufficient specification of outcomes and intended treatment effects. Protocols and SAPs provided more details but were less often available (14% and 3%, respectively), and even then, almost all studies presented limited information to inform the assessments of risk of bias due to the selection of the reported result. CONCLUSION: Lack of full specification of outcomes and intended treatment effects hinder a full adherence of randomized controlled trials of nutrition interventions to transparency practices and may affect their credibility.

Are COVID-19 systematic reviews up to date and can we tell? A cross-sectional study.

BACKGROUND: COVID-19 led to a rapid acceleration in the number of systematic reviews. Readers need to know how up to date evidence is when selecting reviews to inform decisions. This cross-sectional study aimed to evaluate how easily the currency of COVID-19 systematic reviews published early in the pandemic could be determined and how up to date these reviews were at the time of publication. METHODS: We searched for systematic reviews and meta-analyses relevant to COVID-19 added to PubMed in July 2020 and January 2021, including any that were first published as preprints. We extracted data on the date of search, number of included studies, and date first published online. For the search date, we noted the format of the date and where in the review this was reported. A sample of non-COVID-19 systematic reviews from November 2020 served as a comparator. RESULTS: We identified 246 systematic reviews on COVID-19. In the abstract of these reviews, just over half (57%) reported the search date (day/month/year or month/year) while 43% failed to report any date. When the full text was considered, the search date was missing from 6% of reviews. The median time from last search to publication online was 91 days (IQR 63-130). Time from search to publication was similar for the subset of 15 rapid or living reviews (92 days) but shorter for the 29 reviews published as preprints (37 days). The median number of studies or publications included per review was 23 (IQR 12-40). In the sample of 290 non-COVID SRs, around two-thirds (65%) reported the search date while a third (34%) did not include any date in the abstract. The median time from search to publication online was 253 days (IQR 153-381) and each review included a median of 12 studies (IQR 8-21). CONCLUSIONS: Despite the context of the pandemic and the need to easily ascertain the currency of systematic reviews, reporting of the search date information for COVID-19 reviews was inadequate. Adherence to reporting guidelines would improve the transparency and usefulness of systematic reviews to users.

Self-care interventions for preconception, antenatal, intrapartum and postpartum care: a scoping review.

OBJECTIVE: To identify current and emerging self-care interventions to improve maternity healthcare. DESIGN: Scoping review. DATA SOURCES: MEDLINE, Embase, EmCare, PsycINFO, Cochrane CENTRAL/CDSR, CINAHL Plus (last searched on 17 October 2021). ELIGIBILITY CRITERIA: Evidence syntheses, interventional or observational studies describing any tool, resource or strategy to facilitate self-care in women preparing to get pregnant, currently pregnant, giving birth or post partum. DATA EXTRACTION/SYNTHESIS: Screening and data collection were conducted independently by two reviewers. Self-care interventions were identified based on predefined criteria and inductively organised into 11 categories. Characteristics of study design, interventions, participants and outcomes were recorded. RESULTS: We identified eligible 580 studies. Many included studies evaluated interventions in high-income countries (45%) and during antenatal care (76%). Self-care categories featuring highest numbers of studies were diet and nutrition (26% of all studies), physical activity (24%), psychosocial strategies (18%) and other lifestyle adjustments (17%). Few studies featured self-care interventions for sexual health and postpartum family planning (2%), self-management of medication (3%) and self-testing/sampling (3%). Several venues to introduce self-care were described: health facilities (44%), community venues (14%), digital platforms (18%), partner/peer support (7%) or over-the-counter products (13%). Involvement of health and community workers were described in 38% and 8% of studies, who supported self-care interventions by providing therapeutics for home use, training or counselling. The most common categories of outcomes evaluated were neonatal outcomes (eg, birth weight) (31%), maternal mental health (26%) and labour outcomes (eg, duration of labour) (22%). CONCLUSION: Self-care interventions in maternal care are diverse in their applications, implementation characteristics and intended outcomes. Many self-care interventions were implemented with support from the health system at initial stages of use and uptake. Some promising self-care interventions require further primary research, though several are matured and up-to-date evidence syntheses are needed. Research on self-care in the preconception period is lacking.

Conceptualizing the reporting of living systematic reviews.

OBJECTIVES: As part of an effort to develop an extension of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement for living systematic reviews (LSRs), we discuss conceptual issues relevant to the reporting of LSRs and highlight a few challenges. METHODS: Discussion of conceptual issues based on a scoping review of the literature and discussions among authors. RESULTS: We first briefly describe aspects of the LSR production process relevant to reporting. The production cycles differ by whether the literature surveillance identifies new evidence and whether newly identified evidence is judged to be consequential. This impacts the timing, content, and format of LSR versions. Second, we discuss four types of information that are specific to the reporting of LSRs: justification for adopting the living mode, LSR specific methods, changes between LSR versions, and LSR updating status. We also discuss the challenge of conveying changes between versions to the reader. Third, we describe two commonly used reporting formats of LSRs: full and partial reports. Although partial reports are easier to produce and publish, they lead to the scattering of information across different versions. Full reports ensure the completeness of reporting. We discuss the implications for the extension of the PRISMA 2020 statement for LSRs. CONCLUSION: We argue that a dynamic publication platform would facilitate complete and timely reporting of LSRs.

Splinting for carpal tunnel syndrome.

BACKGROUND: Carpal tunnel syndrome (CTS) is a compression neuropathy of the median nerve causing pain and numbness and tingling typically in the thumb, index and middle finger. It sometimes results in muscle wasting, diminished sensitivity and loss of dexterity. Splinting the wrist (with or without the hand) using an orthosis is usually offered to people with mild-to-moderate findings, but its effectiveness remains unclear. OBJECTIVES: To assess the effects (benefits and harms) of splinting for people with CTS. SEARCH METHODS: On 12 December 2021, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, CINAHL, ClinicalTrials.gov, and WHO ICTRP with no limitations. We checked the reference lists of included studies and relevant systematic reviews for studies. SELECTION CRITERIA: Randomised trials were included if the effect of splinting could be isolated from other treatment modalities. The comparisons included splinting versus no active treatment (or placebo), splinting versus another disease-modifying non-surgical treatment, and comparisons of different splint-wearing regimens. We excluded studies comparing splinting with surgery or one splint design with another. We excluded participants if they had previously undergone surgical release. DATA COLLECTION AND ANALYSIS: Review authors independently selected trials for inclusion, extracted data, assessed study risk of bias and the certainty in the body of evidence for primary outcomes using the GRADE approach, according to standard Cochrane methodology. MAIN RESULTS: We included 29 trials randomising 1937 adults with CTS. The trials ranged from 21 to 234 participants, with mean ages between 42 and 60 years. The mean duration of CTS symptoms was seven weeks to five years. Eight studies with 523 hands compared splinting with no active intervention (no treatment, sham-kinesiology tape or sham-laser); 20 studies compared splinting (or splinting delivered along with another non-surgical intervention) with another non-surgical intervention; and three studies compared different splinting regimens (e.g. night-time only versus full time). Trials were generally at high risk of bias for one or more domains, including lack of blinding (all included studies) and lack of information about randomisation or allocation concealment in 23 studies. For the primary comparison, splinting compared to no active treatment, splinting may provide little or no benefits in symptoms in the short term (< 3 months). The mean Boston Carpal Tunnel Questionnaire (BCTQ) Symptom Severity Scale (SSS) (scale 1 to 5, higher is worse; minimal clinically important difference (MCID) 1 point) was 0.37 points better with splint (95% confidence interval (CI) 0.82 better to 0.08 worse; 6 studies, 306 participants; low-certainty evidence) compared with no active treatment. Removing studies with high or unclear risk of bias due to lack of randomisation or allocation concealment supported our conclusion of no important effect (mean difference (MD) 0.01 points worse with splint; 95% CI 0.20 better to 0.22 worse; 3 studies, 124 participants). In the long term (> 3 months), we are uncertain about the effect of splinting on symptoms (mean BCTQ SSS 0.64 better with splinting; 95% CI 1.2 better to 0.08 better; 2 studies, 144 participants; very low-certainty evidence). Splinting probably does not improve hand function in the short term and may not improve hand function in the long term. In the short term, the mean BCTQ Functional Status Scale (FSS) (1 to 5, higher is worse; MCID 0.7 points) was 0.24 points better (95% CI 0.44 better to 0.03 better; 6 studies, 306 participants; moderate-certainty evidence) with splinting compared with no active treatment. In the long term, the mean BCTQ FSS was 0.25 points better (95% CI 0.68 better to 0.18 worse; 1 study, 34 participants; low-certainty evidence) with splinting compared with no active treatment. Night-time splinting may result in a higher rate of overall improvement in the short term (risk ratio (RR) 3.86, 95% CI 2.29 to 6.51; 1 study, 80 participants; number needed to treat for an additional beneficial outcome (NNTB) 2, 95% CI 2 to 2; low-certainty evidence).  We are uncertain if splinting decreases referral to surgery, RR 0.47 (95% CI 0.14 to 1.58; 3 studies, 243 participants; very low-certainty evidence).  None of the trials reported health-related quality of life. Low-certainty evidence from one study suggests that splinting may have a higher rate of adverse events, which were transient, but the 95% CIs included no effect. Seven of 40 participants (18%) reported adverse effects in the splinting group and 0 of 40 participants (0%) in the no active treatment group (RR 15.0, 95% CI 0.89 to 254.13; 1 study, 80 participants).  There was low- to moderate-certainty evidence for the other comparisons: splinting may not provide additional benefits in symptoms or hand function when given together with corticosteroid injection (moderate-certainty evidence) or with rehabilitation (low-certainty evidence); nor when compared with corticosteroid (injection or oral; low certainty), exercises (low certainty), kinesiology taping (low certainty), rigid taping (low certainty), platelet-rich plasma (moderate certainty), or extracorporeal shock wave treatment (moderate certainty). Splinting for 12 weeks may not be better than six weeks, but six months of splinting may be better than six weeks of splinting in improving symptoms and function (low-certainty evidence). AUTHORS' CONCLUSIONS: There is insufficient evidence to conclude whether splinting benefits people with CTS. Limited evidence does not exclude small improvements in CTS symptoms and hand function, but they may not be clinically important, and the clinical relevance of small differences with splinting is unclear. Low-certainty evidence suggests that people may have a greater chance of experiencing overall improvement with night-time splints than no treatment. As splinting is a relatively inexpensive intervention with no plausible long-term harms, small effects could justify its use, particularly when patients are not interested in having surgery or injections. It is unclear if a splint is optimally worn full time or at night-time only and whether long-term use is better than short-term use, but low-certainty evidence suggests that the benefits may manifest in the long term.