Editorial Commentary: Evidence for Patch Augmentation of Rotator Cuff Repair Is Weak.

Rotator cuff repair has a substantial failure rate despite various attempts to improve outcome and prevent a retear. Patch augmentation is an intuitively appealing approach to seek to reduce failure rate and improve outcomes for patients. Two main augmentation approaches are used: "on-lay" and "bridging." The literature is heterogeneous, and the best approach is uncertain. The evidence on patch augmentation for rotator cuff repair is both disparate and weak. Large randomized trials and registry data are required to move the field, ensure patient safety, and avoid wasting precious resources.

How surgical Trainee Research Collaboratives achieve success: a mixed methods study to develop trainee engagement strategies.

OBJECTIVES: This study aimed to understand the role of surgical Trainee Research Collaboratives (TRCs) in conducting randomised controlled trials and identify strategies to enhance trainee engagement in trials. DESIGN: This is a mixed methods study. We used observation of TRC meetings, semi-structured interviews and an online survey to explore trainees' motivations for engagement in trials and TRCs, including barriers and facilitators. Interviews were analysed thematically, alongside observation field notes. Survey responses were analysed using descriptive statistics. Strategies to enhance TRCs were developed at a workshop by 13 trial methodologists, surgical trainees, consultants and research nurses. SETTING: This study was conducted within a secondary care setting in the UK. PARTICIPANTS: The survey was sent to registered UK surgical trainees. TRC members and linked stakeholders across surgical specialties and UK regions were purposefully sampled for interviews. RESULTS: We observed 5 TRC meetings, conducted 32 semi-structured interviews and analysed 73 survey responses. TRCs can mobilise trainees thus gaining wider access to patients. Trainees engaged with TRCs to improve patient care, surgical evidence and to help progress their careers. Trainees valued the TRC infrastructure, research expertise and mentoring. Challenges for trainees included clinical and other priorities, limited time and confidence, and recognition, especially by authorship. Key TRC strategies were consultant support, initial simple rapid studies, transparency of involvement and recognition for trainees (including authorship policies) and working with Clinical Trials Units and research nurses. A 6 min digital story on YouTube disseminated these strategies. CONCLUSION: Trainee surgeons are mostly motivated to engage with trials and TRCs. Trainee engagement in TRCs can be enhanced through building relationships with key stakeholders, maximising multi-disciplinary working and offering training and career development opportunities.

Protocol for a meta-research study of protocols for diet or nutrition-related trials published in indexed journals: general aspects of study design, rationale and reporting limitations.

INTRODUCTION: The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) reporting guideline establishes a minimum set of items to be reported in any randomised controlled trial (RCT) protocol. The Template for Intervention Description and Replication (TIDieR) reporting guideline was developed to improve the reporting of interventions in RCT protocols and results papers. Reporting completeness in protocols of diet or nutrition-related RCTs has not been systematically investigated. We aim to identify published protocols of diet or nutrition-related RCTs, assess their reporting completeness and identify the main reporting limitations remaining in this field. METHODS AND ANALYSIS: We will conduct a meta-research study of RCT protocols published in journals indexed in at least one of six selected databases between 2012 and 2022. We have run a search in PubMed, Embase, CINAHL, Web of Science, PsycINFO and Global Health using a search strategy designed to identify protocols of diet or nutrition-related RCTs. Two reviewers will independently screen the titles and abstracts of records yielded by the search in Rayyan. The full texts will then be read to confirm protocol eligibility. We will collect general study features (publication information, types of participants, interventions, comparators, outcomes and study design) of all eligible published protocols in this contemporary sample. We will assess reporting completeness in a randomly selected sample of them and identify their main reporting limitations. We will compare this subsample with the items in the SPIRIT and TIDieR statements. For all data collection, we will use data extraction forms in REDCap. This protocol is registered on the Open Science Framework (DOI: 10.17605/OSF.IO/YWEVS). ETHICS AND DISSEMINATION: This study will undertake a secondary analysis of published data and does not require ethical approval. The results will be disseminated through journals and conferences targeting stakeholders involved in nutrition research.

Effects of temporarily suspending low-dose methotrexate treatment for 2 weeks after SARS-CoV-2 vaccine booster on vaccine response in immunosuppressed adults with inflammatory conditions: protocol for a multicentre randomised controlled trial and nested mechanistic substudy (Vaccine Response On/Off Methotrexate (VROOM) study).

INTRODUCTION: It is unknown if a temporary break in long-term immune-suppressive treatment after vaccination against COVID-19 improves vaccine response. The objective of this study was to evaluate if a 2-week interruption in low-dose weekly methotrexate treatment after SARS-CoV-2 vaccine boosters enhances the immune response compared with continuing treatment in adults with autoimmune inflammatory conditions. METHODS AND ANALYSIS: An open-label, pragmatic, prospective, parallel group, randomised controlled superiority trial with internal feasibility assessment and nested mechanistic substudy will be conducted in rheumatology and dermatology clinics in approximately 25 UK hospitals. The sample size is 560, randomised 1:1 to intervention and usual care arms. The main outcome measure is anti-spike receptor-binding domain (RBD) antibody level, collected at prebooster (baseline), 4 weeks (primary outcome) and 12 weeks (secondary outcome) post booster vaccination. Other secondary outcome measures are patient global assessments of disease activity, disease flares and their treatment, EuroQol 5- dimention 5-level (EQ-5D-5L), self-reported adherence with advice to interrupt or continue methotrexate, neutralising antibody titre against SARS-CoV-2 (mechanistic substudy) and oral methotrexate biochemical adherence (mechanistic substudy). Analysis of B-cell memory and T-cell responses at baseline and weeks 4 and 12 will be investigated subject to obtaining additional funding. The principal analysis will be performed on the groups as randomised (ie, intention to treat). The difference between the study arms in anti-spike RBD antibody level will be estimated using mixed effects model, allowing for repeated measures clustered within participants. The models will be adjusted for randomisation factors and prior SARS-CoV-2 infection status. ETHICS AND DISSEMINATION: This study was approved by the Leeds West Research Ethics Committee and Health Research Authority (REC reference: 21/HRA/3483, IRAS 303827). Participants will be required to give written informed consent before taking part in the trial. Dissemination will be via peer review publications, newsletters and conferences. Results will be communicated to policymakers. TRIAL REGISTRATION NUMBER: ISRCTN11442263.

Use of implantable meshes for augmented rotator cuff repair: a systematic review and meta-analysis.

OBJECTIVE: To appraise studies reporting on clinical effectiveness and safety of surgical meshes used to augment rotator cuff repairs (RCRs). DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase and Cochrane databases were searched between April 2006 and April 2020. ELIGIBILITY CRITERIA: All studies evaluating adults (≥18 years) undergoing RCR were considered. There were no language restrictions. DATA EXTRACTION AND SYNTHESIS: Screening, data extraction and quality appraisal were conducted by two independent reviewers. Meta-analysis was conducted using a random-effects models if ≥2 comparative studies reported the same outcome measure. Risk of bias assessment was undertaken for randomised (RoB2, Cochrane) and comparative studies (ROBINS-I, Cochrane). RESULTS: We included 60 studies, consisting of 7 randomised controlled trials, 13 observational comparative studies and 40 observational case series. All comparative studies reported on shoulder-specific functional outcome scores, 18 on the radiographic occurrence of re-tear and 14 on pain score metrics. All studies contained some risk of bias.Compared with non-augmented repair, a small improvement in shoulder-specific function or pain scores was observed for synthetic patches with a mean improvement of 6.7 points on the University of California Los Angles (UCLA) shoulder score (95% CI 0.1 to 13.4) and 0.46 point reduction on the Visual Analogue Scale (95% CI -0.74 to -0.17), respectively. A reduced likelihood of radiologically observed re-tear was observed for synthetic (risk ratio (RR) 0.41, 95% CI 0.27 to 0.61) and allograft (RR 0.34, 95% CI 0.18 to 0.65) patches. A total of 49 studies reported on the occurrence of complications. Slightly higher crude complication rates were observed following patch-augmented repair (2.1%) than standard repair (1.6%). CONCLUSIONS: While several studies suggest a decreased failure rate and small improvements in shoulder function and pain following augmented RCR, a paucity of rigorous clinical evaluation, for both effectiveness and safety, prevents firm recommendations. PROSPERO REGISTRATION NUMBER: CRD42017057908.

Correction to: Choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial - the development of the DELTA2 guidance.

Following publication of the original article [1], we have been notified of a few mistakes.

Choosing the target difference and undertaking and reporting the sample size calculation for a randomised controlled trial - the development of the DELTA2 guidance.

BACKGROUND: A key step in the design of a randomised controlled trial is the estimation of the number of participants needed. The most common approach is to specify a target difference in the primary outcome between the randomised groups and then estimate the corresponding sample size. The sample size is chosen to provide reassurance that the trial will have high statistical power to detect the target difference at the planned statistical significance level. Alternative approaches are also available, though most still require specification of a target difference. The sample size has many implications for the conduct of the study, as well as incurring scientific and ethical aspects. Despite the critical role of the target difference for the primary outcome in the design of a randomised controlled trial (RCT), the manner in which it is determined has received little attention. This article reports the development of the DELTA2 guidance on the specification and reporting of the target difference for the primary outcome in a sample size calculation for a RCT. METHODS: The DELTA2 (Difference ELicitation in TriAls) project has five components comprising systematic literature reviews of recent methodological developments (stage 1) and existing funder guidance (stage 2), a Delphi study (stage 3), a 2-day consensus meeting bringing together researchers, funders and patient representatives (stage 4), and the preparation and dissemination of a guidance document (stage 5). RESULTS: The project started in April 2016. The literature search identified 28 articles of methodological developments relevant to a method for specifying a target difference. A Delphi study involving 69 participants, along with a 2-day consensus meeting were conducted. In addition, further engagement sessions were held at two international conferences. The main guidance text was finalised on April 18, 2018, after revision informed by feedback gathered from stages 2 and 3 and from funder representatives. DISCUSSION: The DELTA2 Delphi study identified a number of areas (such as practical recommendations and examples, greater coverage of different trial designs and statistical approaches) of particular interest amongst stakeholders which new guidance was desired to meet. New relevant references were identified by the review. Such findings influenced the scope, drafting and revision of the guidance. While not all suggestions could be accommodated, it is hoped that the process has led to a more useful and practical document.

The curious case of an internal pilot in a multicentre randomised trial-time for a rethink?

Multicentre randomised trials are complex projects with many operational uncertainties. The embedding of a formal check upon study progress and viability at a pre-specified time point (sometimes referred to as an 'internal pilot') is becoming increasingly common within multicentre pragmatic randomised trials. However, it is worth considering this practice. We argue that most, if not all, multicentre trials have reassessment of the recruitment strategy and study processes whilst the study is running. Additionally, we propose discontinuation of the 'internal/external pilot study' terminology. Instead, we suggest for an alternative taxonomy along with greater recognition of the process of refinement which routinely occurs in trials and transparent reporting of it.

Systematic review of the agreement of tonometers with Goldmann applanation tonometry.

OBJECTIVE: To assess the agreement of tonometers available for clinical practice with the Goldmann applanation tonometer (GAT), the most commonly accepted reference device. DESIGN: A systematic review and meta-analysis of directly comparative studies assessing the agreement of 1 or more tonometers with the reference tonometer (GAT). PARTICIPANTS: A total of 11 582 participants (15 525 eyes) were included. METHODS: Summary 95% limits of agreement (LoA) were produced for each comparison. MAIN OUTCOME MEASURES: Agreement, recordability, and reliability. RESULTS: A total of 102 studies, including 130 paired comparisons, were included, representing 8 tonometers: dynamic contour tonometer, noncontact tonometer (NCT), ocular response analyzer, Ocuton S, handheld applanation tonometer (HAT), rebound tonometer, transpalpebral tonometer, and Tono-Pen. The agreement (95% limits) seemed to vary across tonometers: 0.2 mmHg (-3.8 to 4.3 mmHg) for the NCT to 2.7 mmHg (-4.1 to 9.6 mmHg) for the Ocuton S. The estimated proportion within 2 mmHg of the GAT ranged from 33% (Ocuton S) to 66% and 59% (NCT and HAT, respectively). Substantial inter- and intraobserver variability were observed for all tonometers. CONCLUSIONS: The NCT and HAT seem to achieve a measurement closest to the GAT. However, there was substantial variability in measurements both within and between studies.