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Although the theoretical foundations of the modern field of cultural evolution have been in place for over 50 y, laboratory experiments specifically designed to test cultural evolutionary theory have only existed for the last two decades. Here, we review the main experimental designs used in the field of cultural evolution, as well as major findings related to the generation of cultural variation, content- and model-based biases, cumulative cultural evolution, and nonhuman culture. We then identify methodological advances that demonstrate the iterative improvement of cultural evolution experimental methods. Finally, we focus on one common critique of cultural evolution experiments, the appropriate individual learning control condition needed to demonstrate cumulative culture, and present an original experimental investigation relevant to this critique. Participants completed a combinatorial innovation task allowing for cumulative improvement over time in one of four commonly used experimental designs/conditions: social learners in chains, social learners in groups, individual learners experiencing an extended session lasting the same accumulated time as an entire chain or group, and individual learners experiencing repeated sessions adding up to the same total time. We found that repeated individual learning resulted in superior performance to any other condition. We discuss these findings in light of the relevance of the specific criticism of previous experimental studies that purport to have demonstrated cumulative culture. We also use our findings to discuss the broad trade-offs that participants face when learning individually and socially in different contexts, including variable acquisition costs, redundancy of effort in groups, and cognitive and motivational fatigue., Competing Interests: Competing interests statement:The authors declare no competing interest.

As the principal part of acupuncture therapy, acupuncture operators play the key role in clinical effect. There are the inevitably differences in the characteristics among different operators when delivering acupuncture, which may bring a potential impact on the therapeutic effect of acupuncture. However, this impact has not been drawn enough attention in acupuncture research, and the relevant evidences are still contradictory and partially viewed. If ignored, the quality of the relevant outcomes in research is reduced undoubtedly. In order to ensure these problems being realized by more investigators, perfect the clinical design of acupuncture research and improve the quality of acupuncture operation and research, we put forward the theory of the effects of acupuncture operator, analyzed the limitations of current researches in the aspect of the consideration by acupuncture operators and holistic cognition, and provided the corresponding solutions. It is significant in guiding clinical research and practice of acupuncture in future.

The two-trials rule for drug approval requires "at least two adequate and well-controlled studies, each convincing on its own, to establish effectiveness." This is usually implemented by requiring two significant pivotal trials and is the standard regulatory requirement to provide evidence for a new drug's efficacy. However, there is need to develop suitable alternatives to this rule for a number of reasons, including the possible availability of data from more than two trials. I consider the case of up to three studies and stress the importance to control the partial Type-I error rate, where only some studies have a true null effect, while maintaining the overall Type-I error rate of the two-trials rule, where all studies have a null effect. Some less-known P $$ P $$ -value combination methods are useful to achieve this: Pearson's method, Edgington's method and the recently proposed harmonic mean χ 2 $$ {\chi}^2 $$ -test. I study their properties and discuss how they can be extended to a sequential assessment of success while still ensuring overall Type-I error control. I compare the different methods in terms of partial Type-I error rate, project power and the expected number of studies required. Edgington's method is eventually recommended as it is easy to implement and communicate, has only moderate partial Type-I error rate inflation but substantially increased project power., (© 2024 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.)

Background: White matter hyperintensities (WMH) and their progression are associated with risk of dementia and stroke, so are an important target for clinical trials. The cost of broad magnetic resonance imaging (MRI) screening to identify eligible individuals, however, limits the feasibility of designing clinical trials targeting WMH. A low-cost retinal or clinical screening measure before MRI could reduce recruitment costs versus an MRI-only screening design in a hypothetical clinical trial., Methods and Results: Data from the Atherosclerosis Risk in Communities study with valid retinal and WMH measurements ( N =1311) were used. To identify a population at greater likelihood of significant WMH on MRI and thus reduce the number of screening MRIs required, we evaluated 3 theoretical prescreening measures: (1) retinal, (2) clinical, (3) combined clinical-retinal. Given a target sample for clinical trials ( N =646), we calculated screening sample sizes based on the proportion within the population having an elevated score for each prescreening measure (separately) multiplied by the proportion of significant WMH among those with that prescreening feature. Recruitment costs were calculated using estimated retinal and MRI cost estimates. Compared with the estimated cost of MRI-only screening (>$4.24 million, requiring MRI on 6526 participants), prescreening for a high clinical score resulted in total cost of $2.47 million, with an initial screening group of 52 778 participants, with MRI in 3801. A high clinical-retinal score cutoff resulted in costs of $2.9 million while requiring 13 572 participants, with 3801 completing MRI., Conclusions: A 2-stage design with low-cost prescreening measures is a promising approach, resulting in reduced theoretical recruitment costs compared with an MRI-only design.

Background: Process evaluations are increasingly integrated into randomised controlled trials (RCTs) of complex interventions to document their delivery and interactions with local systems and dynamics, helping understand observed health outcomes. Yet process evaluations often struggle to assess relevant contextual determinants, leaving much of the important role of "context" in shaping an intervention's mechanisms opaque in many studies. A lack of easily adapted data collection methods to help define and operationalise indicators of context likely contributes to this., Methods: We present a method to help structure measures of context in process evaluations and describe its use in two very different settings. The "Context Tracker" is an innovative tool for use within trials and quasi-experiments to more systematically capture and understand key dimensions of context. It was developed in Zimbabwe as part of a cluster randomised controlled trial and then adapted for a quasi-experimental evaluation in the UK. Both studies provided harm reduction and health services for marginalised and hard-to-reach populations., Results: We developed the Context Tracker to be both standardised (i.e. formatted and applied in the same way across study sites) and flexible enough to allow unique features to be explored in greater detail. Drawing on the Context and Implementation of Complex Interventions (CICI) and Risk Environments frameworks, we mapped 5 domains across micro, meso and macro levels in a simple table and used existing evidence and experience to predict factors likely to affect delivery of and participation in intervention components. We tracked these over time across study sites using routine programme statistics, observation and qualitative methods. The Context Tracker enables identification and comparison of facilitators and barriers to implementation, variations in engagement with interventions, and how mechanisms of action are (or are not) triggered in different settings., Conclusions: The Context Tracker is one example of how evidence-based contextual determinants can be used to guide data collection and analysis within process evaluations. It is relevant in low- and high-income settings and applicable to both qualitative and quantitative analyses. While perhaps most useful to process evaluations of complex interventions targeting marginalised communities, the broader approach would benefit a more general research audience., Competing Interests: Declarations Ethics approval and consent to participate The AMETHIST study received ethical approval from the Medical Research Council of Zimbabwe (MRCZ/A/2559), Liverpool School of Tropical Medicine (19-115RS) and London School of Hygiene and Tropical Medicine (19123). The SIPP study received ethical approval from the London School of Hygiene & Tropical Medicine Research Ethics Committee (28102). Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Introduction: Hospitals are vital infrastructures that provide health services during emergencies and disasters. However, in recent years, disasters have led to hospital losses and interruptions in medical services. Consequently, the concept of resilience has garnered significant attention. Despite extensive research, the lack of clarity in explaining hospital resilience poses challenges in effective assessment and identifying key priorities for enhancing disaster risk management. Recently, the WHO's Eastern Mediterranean Regional Office (EMRO) introduced a conceptual framework for the conceptualisation of hospital resilience, defining it through six interconnected components and four resilience capacities. Identifying specific indicators and characteristics for hospital resilience components based on the EMRO framework. This protocol outlines the method for conducting a scoping review to identify such indicators and characteristics to develop a comprehensive hospital resilience assessment tool., Methods and Analysis: This scoping review will adhere to the six-step protocol proposed by Arksey and O'Malley. It aims to comprehensively understand current knowledge about resilient hospital characteristics and identify effective components and indicators for assessing hospital resilience. The review will encompass available articles indexed in PubMed, Scopus and Web of Science. Additionally, searches will explore the grey literature on Google Scholar, the WHO's website and regional offices. There will be no publication date restrictions applied to the search. Quantitative and qualitative content analyses will assess and categorise the study results. Our protocol was drafted using the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols extension for scoping reviews., Ethics and Dissemination: This protocol describes a scoping review within a doctoral thesis focused on health in emergencies and disasters, specifically hospital resilience. The study, associated with ethics code number (IR.USWR.REC.1402.120), aims to develop a comprehensive assessment tool for hospital resilience. Once peer-reviewed and published, the findings will inform experts, policymakers and relevant organisations in emergency and disaster management., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Tandem Spinal Stenosis (TSS) is a disease characterised by the narrowing of the spinal canal in two or more non-adjacent areas of the spine, often affecting both the cervical and lumbar vertebrae. Doctors and patients increasingly favour non-surgical treatments that have the function of relieving symptoms and improving outcomes. This systematic review aims to evaluate the effectiveness and safety of non-surgical therapies for TSS and comprehensively summarise existing evidence., Methods and Analysis: We will conduct comprehensive searches, both manual and electronic, of literature published up to 30 September 2024; database searches will commence after the publication of this agreement, with an estimated commencement date of 1 December 2024, and the end date is 31 May 2025, without language restrictions. Key databases such as MEDLINE, PubMed, EMBASE, Web of Science, Cochrane Library, WHO International Clinical Trial Registration Platform, China National Knowledge Infrastructure, China Biomedical Literature Database, China Scientific Journal Database and Wan-Fang Database will be explored. In addition, we will include resources such as library journals and conference abstracts. Following the identification and screening of all randomised controlled trials focusing on non-surgical treatments for TSS, two investigators will perform a meta-analysis of the included studies. The findings will be summarised as the risk ratio for binary data and the standardised or weighted mean difference for continuous data., Ethics and Dissemination: Ethical approval is not required, as the review does not involve individual patient data. The review's findings will provide clinicians with evidence on using non-surgical treatments for TSS, disseminated through peer-reviewed publications or conferences., Prospero Registration Number: CRD42024496634., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Tonsillitis is a self-limiting inflammatory process of the tonsils. In high-income countries, guidelines have been developed to decide if a patient needs an antibiotic or not. These guidelines help to reduce unnecessary antibiotic prescriptions and prevent the development of antimicrobial resistance (AMR). In low- and middle-income countries (LMICs), medical practitioners have the tendency to prescribe antibiotics in all cases of tonsillitis; there is an overprescription of antibiotics. These prescriptions are probably unjustified and seem to be responsible for the increased AMR seen in developing countries. The aim of this review will be to estimate the proportion of unjustified antibiotic prescriptions in LMICs., Methods and Analysis: We will conduct a systematic review of all observational studies on the diagnosis and treatment of tonsillitis in LMICs. The selected database will include PubMed, Web of Sciences Global Index Medicus and the Grey literature. The search will include studies published from January 2012 until December 2024. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and bias will be assessed by a Risk of Bias Assessment Tool for observational studies by Hoy et al . A meta-analysis will be conducted for homogeneous studies, eventually using the random effect model. Subgroup analysis will include a period of study, study quality, countries and/or subregions of LMICs involved, study setting, age of participants, tools and definition used., Ethics and Dissemination: Formal ethical approval is not required, as primary data will not be collected. The results will be disseminated through peer-reviewed publications and presented at scientific conferences., Prospero Registration Number: CRD 42022384957., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Interstitial lung diseases (ILDs), encompassing both pediatric and adult cases, present a diverse spectrum of chronic conditions with variable prognosis. Despite limited therapeutic options beyond antifibrotic drugs and immunosuppressants, accurate diagnosis is challenging, often necessitating invasive procedures that may not be feasible for certain patients. Drawn against this background, experts across pediatric and adult ILD fields have joined forces in the RARE-ILD initiative to pioneer novel non-invasive diagnostic algorithms and biomarkers. Collaborating with the RARE-ILD consortium, the eurILDreg aims to comprehensively describe different ILDs, analyze genetically defined forms across age groups, create innovative diagnostic and therapeutic biomarkers, and employ artificial intelligence for data analysis., Methods: The foundation of eurILDreg is built on a comprehensive parameter list developed and adopted by clinical experts, encompassing over 1,800 distinct parameters related to patient history, clinical examinations, diagnosis, lung function and biospecimen collection. This robust dataset is further enriched with daily assessments captured through the patientMpower app, including handheld spirometry and exercise tests, conducted on approximately 350 patients over the course of a year. This approach involves app-based daily assessments of quality of life, symptom tracking, handheld spirometry, saturation measurement, and the 1-min sit-to-stand test (1-STST). Additionally, pediatric data from the ChILD-EU registry will be integrated into the RARE-ILD Data Warehouse, with the ultimate goal of including a total of 4.000 ILD patients and over 100.000 biospecimen., Discussion: The collaborative efforts within the consortium are poised to streamline research endeavors significantly, promising to advance patient-centered care, foster innovation, and shape the future landscape of interstitial lung disease research and healthcare practices., Trial Registration: EurILDreg is registered in the German Clinical Trials Register (DRKS 00028968, 26.07.2022), and eurIPFreg is registered in ClinicalTrials.gov (NCT02951416)., Competing Interests: Declarations Ethics approval and consent to participate The ethics committee of the Justus Liebig University of Giessen has approved the eurILDreg as extension of eurIPFreg under protocol reference number 111/08. Additionally, approval from the medical ethics committee at each participating site will be obtained prior to patient inclusion. Written informed consent will be obtained from all participants. The study will be conducted in accordance with the Declaration of Helsinki. Consent for publication All authors gave their consent for publication. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: It is important to incorporate the patient perspective into healthcare education, as we know that patients are experts in their own conditions. The expertise gained through lived experience serves to complement the theoretical knowledge that healthcare educators can provide. This scoping review aims to explore patient involvement in medical education within obstetrics and gynaecology, a specialty that can provide unique challenges and complexities to patient involvement due to its potentially highly sensitive and intimate nature. The goal of this study is to map the available literature on this topic which will allow for the identification of potential gaps in the provision of training for medical students in this field. The research also aims to highlight challenges that may be associated with patient involvement in this specialty in order to guide future initiatives., Methods and Analysis: The Joanna Briggs Institute scoping review framework and methodology will be used to guide and conduct this scoping review. A systematic search of electronic databases MEDLINE, CINAHL, Embase, Scopus, PsycINFO, ERIC, Google Scholar, Web of Science, African Journals Online, Cochrane Library and SciVerse will be carried out. Articles will be limited to the English language. No geographical limitations will be placed on the search. Literature from 1960 to 2023 will be considered for inclusion which corresponds with the first reports of patient educators used to assist with the demonstration of clinical skills in obstetrics and gynaecology. Relevant academic journals will be hand-searched for the previous 5 years. Identified studies will be screened by two independent reviewers and data extraction carried out by the primary researcher. Key findings will be presented in tables and summarised in narrative form. Findings from the review will be reported according to the PRISMA Extension for Scoping Reviews reporting checklist., Ethics and Dissemination: Ethical approval is not required for this study. The findings from the study will be submitted for publication in peer-reviewed journals and at medical education conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Perianal fistulising Crohn's disease (pfCD) is a distinct and debilitating phenotype seen in around one-third of patients with CD. Clinical trials in pfCD are increasingly using magnetic resonance imaging (MRI) criteria as a primary endpoint, but there is heterogeneity in the radiological definition of a healed perianal fistula that currently limits our ability to perform meaningful meta-analyses of studies. Our aim is to standardise outcomes through the generation of an international consensus definition of a radiologically healed fistula., Methods and Analysis: This international Delphi consensus study employs a two-part strategy.The first is a systematic review to identify a longlist of variables used to define radiological healing in pfCD. MRI-based indices used to score fistula severity and healing will be assessed for their methodological quality using Consensus-based Standards for the selection of health Measurement Instruments (COSMIN). The systematic review protocol will be conducted using COSMIN methodology and reported using Preferred Reporting Items for Systematic Reviews and Meta-Analyses.The second part will be an online Delphi consensus, guided by the results of the systematic review. Radiologists, gastroenterologists and colorectal surgeons with expertise in the management of pfCD will be invited to take part in two to three rounds of online surveys. Once an a priori threshold of >80% agreement is reached on individual radiological components used to define 'healing' and 'healed', a final meeting of key stakeholders will be organised to generate a consensus definition of a healed fistula., Ethics and Dissemination: The study has been deemed exempt from a formal Research Ethics Committee review as no patients will participate directly in the consensus process, given the technical nature of the research question. The study is registered with the local R&D department (Reference RD24/007). Publication of this study will help standardise radiological endpoint measurement in clinical trials of pfCD and improve the synthesis and meta-analysis of comparative studies., Prospero Registration Number: CRD42024504334., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Life satisfaction is a key indicator of successful ageing and reflects well-being. There is evidence of the association between life satisfaction and health behaviours among older adults. Therefore, this systematic review and meta-analysis protocol seeks to determine the strength and direction of the association between life satisfaction and health behaviours among older adults., Methods and Analysis: This protocol followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search the electronic databases (MEDLINE, APA PsycINFO, Web of Science, CINAHL and Global Health) from inception to date. Only observational studies that described the association between life satisfaction and health behaviours-smoking, alcohol drinking, physical activity, diet/nutrition and sleep-will be included. Two independent reviewers will conduct screening, data extraction and risk of bias assessment of the articles. The risk of bias will be assessed using the Joanna Briggs Institute critical appraisal tools for cohort and analytical cross-sectional studies. Studies will be included in the meta-analysis if they report zero-order associations between life satisfaction and health behaviours; otherwise, a narrative synthesis will be presented., Ethics and Dissemination: This study does not require ethics approval, as it involves analysing secondary data from published studies. The completed review will be published in a peer-reviewed journal and presented at conferences., Trial Registration Number: PROSPERO (CRD42023441386)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The available literature reviews of shift work among care workers are almost exclusively focused on 8-hour shifts and 12-hour shifts or 24-hour on-call shifts for physicians. We do not yet know the scope of evidence regarding extended-duration work shifts (defined as on-duty shifts of 16 or more hours per shift) in diverse healthcare settings, such as the impact on care workers and recipients of care. In this proposed scoping review, we aim to provide an overview of the current research regarding extended-duration work shifts among care workers in various healthcare settings., Methods and Analysis: We will conduct this scoping review in accordance with the Joanna Briggs Institute scoping review methodology. Comprehensive searches will be conducted in PubMed, Embase, MEDLINE, Web of Science and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases and grey literature sources. We will include empirical studies that focus on extended-duration work shifts among care workers working in different healthcare settings, including home care, community, acute care settings, long-term care homes and assisted living facilities. We will not apply language restrictions. We will conduct searches in August 2024, followed by screening of records. We will exclude research on on-call work shifts and investigations that solely focus on interns. The included literature will be screened independently by pairs of reviewers at the title and abstract review phase, followed by a full-text review for relevant literature. Any disagreement will be resolved by consensus or discussion with a third reviewer. The results will be extracted and summarised in the final report in tabular form, when possible, along with narrative synthesis., Ethics and Dissemination: All data for this study will come from published literature, so an ethics review is not necessary. The findings will be disseminated through conference presentations and publication in peer-reviewed journals, with the expectation that they will guide future research and inform future management of work shifts in care workers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Carbapenems are used to treat multidrug-resistant organisms as last-resort antibiotics. Resistance to carbapenems is an emerging public health threat worldwide, with alarming reported rates in Asian countries. To minimise further spread of resistant strains and guide interventions, it is important to understand the prevalence rates and causative molecular determinants. Therefore, the systematic review and meta-analysis arising from this protocol will aim to comprehensively describe the available surveillance data on carbapenem resistance in Asian countries to provide an in-depth overview of the carbapenem resistance status in this region., Methodology and Analysis: A systematic review and meta-analysis will be conducted via PubMed, ScienceDirect, Cochrane Library and Web of Science databases. Additional articles and grey literature will be searched in Google Scholar, OpenGrey and Google Chrome by manually searching the reference lists of selected studies. The review question was designed according to components in the ECLIPSE (E-expectations, C-client, L-location, I-impact, P-profile and S-service) framework. Studies conducted with samples other than clinical samples will be excluded. Only original articles published in the English language will be included. The Joanna Briggs Institute critical appraisal tool will be used to assess the quality of the included studies. A random-effects meta-analysis will be performed if the data are sufficiently homogenous. Heterogeneity between studies will be assessed via the I² statistic. The subgroup analysis will be performed considering the type of sample, pathogen type, region/country where the studies were conducted and genetic determinants., Ethics and Dissemination: As this study is conducted on the basis of published data, ethical approval is exempt. The findings of this study will be disseminated in a peer-reviewed journal with the intention of providing summarised data on the globally emerging threat of carbapenem resistance and emphasising the need to introduce alternative, more effective treatment options., Prospero Registration Number: CRD42024515806., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Somatic symptom disorder (SSD) is a distressing mental disorder characterised by the presence of at least one persistent somatic symptom and a significant psychological burden due to the symptom(s), as well as excessive thoughts, feelings or behaviours related to them or associated health concerns. The primary aim of our study is to deepen the understanding of risk factors and mechanisms for somatic symptom persistence. Specifically, we will investigate the role of patients' expectations and somatic comorbidity regarding symptom persistence., Methods and Analysis: In a prospective 12-month cohort study, n=240 patients with SSD will be recruited from the outpatient clinics of the Department of Psychosomatic Medicine and Psychotherapy at the University Medical Center Hamburg-Eppendorf. The roles of two hypothesised predictors (ie, expectations and comorbidity) will be analysed together with known predisposing and maintaining factors of persistent somatic symptoms. The study entails macrolevel and microlevel assessments to investigate symptom severity over different timespans. Assessments at the macrolevel take place at baseline, 6 and 12 months. At the microlevel, a 10-day ecological momentary assessment study will be implemented to elucidate patients' dynamic experience with somatic symptoms in their natural environments. In order to elicit possible framing effects on the 10-day course of symptom severity, participants are randomised to either a positive or a negative expectation framing group. Cross-lagged panel models will be used to analyse data at the macrolevel. At the microlevel, multivariate latent growth curve models will be conducted to relate temporal changes in predictor and outcome variables to one another., Ethics and Dissemination: The study was approved by the Ethics Committee of the Medical Associations Hamburg, Germany (2020-10197-BO-ff). The results will enable us to draw conclusions regarding the role of expectations for future targeted treatment options and regarding the utility of somatic comorbidity as a potential diagnostic specifier of SSD. Dissemination of our results will be achieved through scientific publications, and lay summaries for study participants, patient advocacy groups and the general public., Trial Registration Number: ISRCTN36251388., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: This systematic review aims to evaluate the methodology used in pancreatic cancer (PC) randomised controlled trials (RCTs) measuring quality of life (QOL) and focuses on the type, frequency, survey compliance and duration of these assessments., Design: Systematic review of PC RCTs measuring QOL., Data Sources: A search of PubMed.gov and ClinicalTrials.gov was conducted for PC RCTs measuring QOL from inception to 21 March 2023. Only phase III RCTs were included. Studies were excluded if QOL was not measured, the study was phase I/II, in the second-line setting or unavailable in English. Data were independently extracted by two reviewers in a standardised fashion., Primary and Secondary Outcome Measures: Primary outcomes included the type of QOL instrument used, the timing and frequency of assessments, methods of analysis and survey completion rates (SCRs) over time. Secondary outcomes included patient demographics, significant QOL improvements and the frequency of trials measuring QOL., Results: Out of 269 studies screened, 54 RCTs were identified, and 24 measured QOL (involving 11 229 patients). Instruments used included the EORTC QLQ-C30 (n=15), FACT-HEP (n=3), Spitzer-QOL-Index (n=2), EQ-5D (n=2), LASA (n=1) and FACT-PA (n=1). Most trials assessed QOL until disease progression or death (10/24), with 4-week intervals being the most common (7/24). SCRs were reported in 15/24 trials, with disease stage influencing SCRs over time. In trials with metastatic, locally advanced/metastatic, and resectable disease, the median times to reach a 50% response rate-defined as the point where the number of surveys completed was half of the enrolled participants-were 12.41 weeks (n=2), 14.14 weeks (n=10), and 54.2 weeks (n=3), respectively." Only 2/24 trials reported significant QOL improvements between treatment arms. Patient age was reported in all trials, while race/ethnicity was only reported in 4/24 trials., Conclusions: Significant variability exists in the timing, methods and reporting of QOL assessments in PC trials. There is a need for further research to assess the implications of missing data and consider the temporality of QOL assessment in patients with advanced cancers and poor prognosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: A clinical prediction tool to estimate life expectancy in community-dwelling individuals living with dementia could inform healthcare decision-making and prompt future planning. An existing Ontario-based tool for community-dwelling elderly individuals does not perform well in people living with dementia specifically. This study seeks to develop and validate a clinical prediction tool to estimate survival in community-dwelling individuals living with dementia receiving home care in Ontario, Canada., Methods and Analysis: This will be a population-level retrospective cohort study that will use data in linked healthcare administrative databases at ICES. Specifically, data that are routinely collected from regularly administered assessments for home care will be used. Community-dwelling individuals living with dementia receiving home care at any point between April 2010 and March 2020 will be included (N≈200 000). The model will be developed in the derivation cohort (N≈140 000), which includes individuals with a randomly selected home care assessment between 2010 and 2017. The outcome variable will be survival time from index assessment. The selection of predictor variables will be fully prespecified and literature/expert-informed. The model will be estimated using a Cox proportional hazards model. The model's performance will be assessed in a temporally distinct validation cohort (N≈60 000), which includes individuals with an assessment between 2018 and 2020. Overall performance will be assessed using Nagelkerke's R 2 , discrimination using the concordance statistic and calibration using the calibration curve. Overfitting will be assessed visually and statistically. Model performance will be assessed in the validation cohort and in prespecified subgroups., Ethics and Dissemination: The study received research ethics board approval from the Sunnybrook Health Sciences Centre (SUN-6138). Abstracts of the project will be submitted to academic conferences, and a manuscript thereof will be submitted to a peer-reviewed journal for publication. The model will be disseminated on a publicly accessible website (www.projectbiglife.com)., Trial Registration Number: NCT06266325 (clinicaltrials.gov)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Data sharing, the act of making scientific research data available to others, can accelerate innovation and discoveries, and ultimately enhance public health. The National Cancer Institute Implementation Science Centers in Cancer Control convened a diverse group of research scientists, practitioners, and community partners in three interactive workshops (May-June 2022) to identify and discuss factors that must be considered when designing research for equitable data sharing with a specific emphasis on implementation science and social, behavioral, and population health research. This group identified and operationalized a set of seven key considerations for equitable data sharing-conceptualized as an inclusive process that fairly includes the perspectives and priorities of all partners involved in and impacted by data sharing, with consideration of ethics, history, and benefits-that were integrated into a framework. Key data-sharing components particularly important for health equity included: elevating data sharing into a core research activity, incorporating diverse perspectives, and meaningfully engaging partners in data-sharing decisions throughout the project lifecycle. As the process of data sharing grows in research, it is critical to continue considering the potential positive and adverse impact of data sharing on diverse beneficiaries of health data and research., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Behavioral Medicine.)

The success of therapeutic monoclonal antibodies (mAbs) and their biosimilars, highlights the challenge to control their purity, identity, and stability. For this purpose, among several orthogonal methodologies, imaged capillary Iso Electric Focusing (icIEF) is one of the leading techniques. Despite the isoelectric point (pI) being a univocal parameter relying on the protein's primary sequence and its post-translational modifications (PTMs), the current Charge Variants Profile Assessment (CVPA) carried out by cIEF relies on relative comparisons with corresponding reference standards, this is because the inconsistent outputs for the same sample across different instruments preclude the uniqueness of the measured parameters. We demonstrate that refining the current calibration approach in the iciEF method allows for obtaining more reliable and objective pIs, and a deeper understanding of the pH gradients along the capillaries. We are confident our advancements will enhance CVPA, by exploring the concept of univocal charge identity. This is crucial for constructing biobanks and developing algorithms to quickly identify divergences from the originators, thus ensuring drug quality, efficacy, and safety. Moreover, our method allows an experimental design optimized to minimize bias ("Unbiased" Experimental Design-UED) to study resolution as a multivariate function of different input variables. This endeavor aims to develop optimal methods tailored to specific pH ranges., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: The benefits of randomised trials are not shared equally, and people from ethnic minority groups are a key constituency under-served by clinical research and clinical care. The STRIDE project aimed to give trialists practical information about how to decide which ethnic groups should be in their trials, and at what proportion., Methods: We considered trials in six clinical areas: cancer, cardiovascular, diabetes, maternal health, mental health, and smoking cessation. We created a summary for each, including participants-intervention-comparators-outcomes, and data on disease prevalence by ethnicity. These were discussed with panels with clinical expertise, trial and methodology expertise, lived experience, funding, and experience of working with and on behalf of ethnic communities. For each trial, we asked panel members to decide which ethnic groups should have been involved and at what proportion., Results: We discussed 23 trials with 40 individual panel members. Panels found our questions difficult to answer. The lack of publicly available data on prevalence by ethnicity was central to this. Where data were available, decision-making was easier but not simple. The discussions led to eight STRIDE recommendations. We recommend that discussions involve diverse teams and that discussions need time, with access to the best available data. In the absence of data or consensus, we recommend the adoption of 'default' minimum rates of inclusion, with oversampling considered. These discussions should inform site selection, and the practical challenges of recruitment and retention should not determine which groups are to be included. We also suggest five policy initiatives to support implementation of the recommendations. Broadly, these are (1) funders need to signal that ethnic diversity is expected, (2) trial teams need access to better data, (3) funders and others need to signal that ethnic diversity means better science, (4) more funding is needed for evaluation, and (5) Good Clinical Practice training should cover ethnic diversity., Conclusions: Agreeing targets for which ethnic groups to involve in a trial is essential but difficult. Our eight recommendations could help to make trials more ethnically diverse if followed, and we suggest five policy initiatives that would create a supportive environment for their implementation., Competing Interests: Declarations Ethics approval and consent to participate Ethics approval was not required for this work. Members of the public who took part did so as patient and public partners helping to drive and shape the work, not as research participants. Consent for publication Not applicable for this article. Competing interests KK is Director for Centre for Ethnic Health Research, University of Leicester, UK. ST is an Editor-in-Chief of Trials. All other authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Climate change impacts the circumpolar region (including northern Canada) at a greater magnitude than other parts of the world. This affects food (in)security as well as food sovereignty. This scoping review aims to map the methods of measuring food (in)security and food sovereignty across northern Canada and the circumpolar region in support of the Yukon Government's climate change adaptation strategy., Methods and Analysis: We will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews, and work will be conducted according to the Joanna Briggs Institute (JBI) manual chapter on scoping reviews. Academic librarians develop the academic literature and grey literature search strategies, and the search strategies are further revised through iterative stages of peer review. The search strategy includes 7 academic literature databases, 11 grey literature databases, over 50 websites and the University of Toronto Libraries catalogue. Covidence, an evidence synthesis software, will be used for screening and extraction. The extraction chart will be developed and piloted by our team. A minimum of two reviewers will conduct screening, and conflicts will be resolved through discussion. Data will be extracted by one reviewer and verified by a second. Conflicts will be resolved through discussion or by a third reviewer., Ethics and Dissemination: This project does not require ethical approval as it is secondary research; data will be extracted from published academic research papers, dissertations, and publicly available reports and documents. Our dissemination plan includes presentations at conferences, submission to international peer-reviewed journals and a workshop on the search strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Early in the COVID-19 pandemic, numerous clinical trials were initiated. Although concerns were raised regarding the quality of the trials, the eventual research output yielded from the trials remains unknown. The objective of this study was to include all clinical trials registered on ClinicalTrials.gov during the first 6 months of the pandemic and assess if and where their results had been reported, their completion and discontinuation rates, achieved enrolment and changes made to the primary outcome after trial registration., Methods: We included all interventional studies related to COVID-19 first registered on ClinicalTrials.gov between 1 January 2020 and 1 July 2020. We systematically searched for trial results, reported through 15 May 2023, in scientific publications, preprints and ClinicalTrials.gov. We assessed the achieved trial enrolment, trial discontinuation (reaching <90% of target enrolment), and whether the primary outcome had been changed as compared with the initial protocol registration., Results: The 775 clinical trials included in the analysis planned to enrol 238 933 (median (IQR) 120 (60, 304) patients; 355 (46%) of the trials had reported results, and 283 (36%) were published in a scientific journal. In the reported trials, the total enrolment was 95 332 (median (IQR) 105 (45, 222) patients. 186 (24%) trials were completed, and 169 (22%) trials were discontinued, with slow recruitment being the most stated reason for discontinuation (9% of all trials, although 30% of the discontinued trials did not report a reason). 117 (33%) of the reported trials had changed their primary outcome. In total, 157 (20%) trials were completed and published in a scientific journal, of which 105 enrolled ≥100 patients and 103 had not changed the primary outcome. 63 completed and published trials enrolled ≥100 patients and had not changed the primary outcome., Conclusions: Most clinical trials of COVID-19 registered at ClinicalTrials.gov during the first 6 months of the pandemic remained unreported or had been discontinued. Many of the trials whose results had been reported enrolled few patients and changed the primary outcome after trial registration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Adolescent mental health is a global public health challenge as most cases remain undetected and untreated, and consequently, have a high likelihood of persistence or recurrence. It is critical to improve early detection of mental disorders and to target individuals experiencing subclinical symptoms. However, most indicated prevention approaches have been developed for risk syndromes of specific mental disorders. This contradicts the increasing recognition of emerging psychopathology as a complex system characterised by rapid shifts in subclinical symptoms, cutting across diagnostic categories and interacting with each other over time. Therefore, this study aims to examine the dynamic course, pattern and network of subclinical symptoms and transdiagnostic mechanisms over time., Method and Analysis: The EMERGE-study is a prospective, naturalistic, 1-year follow-up study. A general population sample of 1196 adolescents will be recruited. Inclusion criteria are age between 11 and 17 years, German language skills, main residency in Switzerland and access to internet. Individuals will be excluded if they have a current or lifetime axis I mental disorder. Assessments of subclinical symptoms of several mental disorders and potential transdiagnostic mechanisms will be conducted at baseline and at 3-month, 6-month, 9-month and 12-month follow-up. Structural equation modelling will be used to estimate the homotypic and heterotypic patterns of subclinical symptoms and the associations with transdiagnostic mechanisms. Latent growth mixture modelling and growth mixture survival analysis will be carried out to identify subclasses of individuals with different trajectories of subclinical symptoms that may be predictive of an onset of a mental disorder. Network analysis will be applied to assess the centrality of subclinical symptoms and how networks of emerging psychopathology change over time., Ethics and Dissemination: Ethical approval was obtained from the Bern Cantonal Ethics Committee (ID 2020-02108). All findings will be disseminated by publication in peer-reviewed scientific journals and by presentation of the results to conferences and stakeholder organisation events., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Teleworking is one of the most significant legacies of the pandemic. Great attention is now being paid to its effects on workers' health. One of the arguments that emerged on this issue is that 'working away from the office' affects the time we spend with significant others. This calls into question all those processes that make relatives and colleagues important to our health, such as forms of mentoring and social support, but also conflicts, work interruptions or control over workers' activities. So far, no study has evaluated the impact that teleworking has on these processes using data on personal networks. The Empty Office is the first study to use social network analysis to measure the impact that telework has on social relations and, in turn, workers' health and well-being., Methods and Analysis: The project draws on a total sample of 4400 participants from Switzerland, the Netherlands, Spain and Germany (n=1100 per country). The choice of these countries is due to their specificity and diversity in socioeconomic features, which make them particularly interesting for studying teleworking from a comparative point of view. The research is conceived as a sequential mixed-method design. First, quantitative data collection will administer an online questionnaire to gather information on telework modalities, health and well-being markers, and data on personal networks collected by a name generator. A qualitative module, administered one year later, will consist of in-depth interviews with a subsample (n=32) of teleworkers selected for delving narratively into the mechanisms identified with the quantitative analyses., Ethics and Dissemination: This study has obtained 2 years of funding from the Swiss Network for International Study and was approved by the Ethics Committee of the University of Geneva (CUREG-20230920-292-2). All participants will be asked to provide informed consent to participate in this study. The results will be shared with international organisations and disseminated in scientific journals and conferences. Fully anonymised data will be made available on the Open Science Framework (OSF) data-repository platform., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Human papillomavirus (HPV) infection is the most prevalent sexually transmitted infection worldwide. HPV vaccination is an important tool to prevent and control HPV infection and its complications. Despite carrying the severe burden of disease, HPV vaccine coverage in Africa remains low. The aim of the current review is to evaluate the factors associated with HPV vaccination acceptance among adolescent men and women, young men and women, parents/caregivers, men who have sex with men, healthcare workers and programme managers in Africa., Methods and Analysis: We will include peer-reviewed quantitative studies. We will search PubMed, Scopus, PsycInfo, Web of Science and Cochrane Central Register of Controlled Trials, with no language restriction, to identify eligible studies. Two review authors will independently screen the titles and abstracts of the search output in Covidence to select potentially eligible studies. The same two reviewers will independently screen the full-text of all identified potentially eligible articles to identify studies meeting inclusion criteria. Two review authors will independently extract data from eligible studies using a predefined data extraction form. Two review authors will independently assess the risk of bias in each included study, using the Effective Public Health Practice Project 'Quality Assessment Tool for Quantitative Studies'. We will assess the quality of evidence using the method for Grading of Recommendations Assessment, Development and Evaluation., Ethics and Dissemination: Ethical approval is not required for this study because we will use already published data. The results of this review will be disseminated through peer-reviewed publication and conference presentation., Prospero Registration Number: CRD42023475810., Competing Interests: Competing interests: CSW serves on the Editorial Advisory Board of BMJ Open., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with kidney failure often lack robust evidence because they are excluded from randomized trials. Trial emulation provides an alternative approach to derive treatment effect estimates when randomized trials cannot be conducted. Critical questions about the comparative efficacy and safety of interventions in kidney failure are now being answered using this approach or parts of it. However, variations and inconsistencies in reporting cast doubt on the reliability and validity of effect estimates not derived from randomized trials. The aim of this methodological systematic review is to understand the extent to which the target study approach is used in kidney failure and the appropriateness of this approach. By identifying and evaluating studies that qualify as emulating a target trial, compared with studies that did not apply the principles. We aim to provide more specific methodological guidance to increase the clarity and reliability of reporting treatment effect estimates when running a trial in kidney failure is not feasible., Methods: This protocol is developed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocols (PRISMA-P) statement. MEDLINE, Embase, and reference lists (backwards citation chasing) will be searched up until 1st July 2023 and the search updated prior to publication to identify all studies evaluating patient outcomes in late-stage kidney disease and failure that use target trial emulation as the primary approach for analysis. Two authors (A. A., P. K.) will select articles based on title and abstract and then full text, with a third reviewer settling disagreements (J. P.). The prespecified variables will be extracted, and the risk of bias will be assessed by at least two authors (A. A., P. K., A. N.) using prespecified data forms. This will enable the determination of the robustness of the methodological quality of observational studies in using the whole or elements of the target trial approach. We will thereby assess their ability to reliably report treatment effect estimates., Discussion: We will provide specific methodological recommendations on how to design target trials and model assumptions for emulation to get reliable treatment effect estimates for therapeutic interventions in kidney failure., Methodological Systematic Review Registration: Open Science Framework: Identifier https://doi.org/10.17605/OSF.IO/Z4Y29 ., Competing Interests: Declarations Ethics approval and consent to participate The protocol plan does not contain active involvement of participants which would require ethical consent. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Objectives: Most first-time biomedical research grant applications are not funded. In the challenging research funding climate, resubmitting a grant application is a necessary task for scientists. Identifying which factors influence their decision to resubmit and the success of resubmissions will inform funders and applicants. However, data on resubmissions are fragmented and under-reported. In this scoping review, we aimed to summarise (1) the outcomes of resubmitting biomedical research grant applications and (2) the demographic characteristics of scientists who resubmitted grant applications., Design: Scoping review with reporting informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses., Data Sources: MEDLINE, CINAHL, EMBASE, Cochrane Central Registrar of Controlled Trials CENTRAL, PsycINFO, Web of Science and grey literature sources were searched through November 2022., Eligibility Criteria: We included peer-reviewed and grey literature records from the biomedical sciences that reported outcomes of the resubmission process (eg, resubmission success rate, rate of resubmission) and information about the scientists who resubmit grant applications (eg, sex, race, career stage)., Data Extraction and Synthesis: Data were extracted independently by two reviewers. The data were cross-referenced and any conflicts were resolved via consensus. Data were summarised descriptively and presented in tables and figures., Results: Resubmissions represented a substantial proportion of applications (lowest prevalence rate: 4%; highest prevalence rate: 56%) in a given funding cycle and were reliably more successful than first-time applications (lowest success rate: 16%; highest success rate: 82%)-a phenomenon associated with several sociodemographic, institutional and project-related factors. There was conflicting evidence about the relationship of sociodemographic-related, institution-related and project-related factors to resubmission likelihood and success., Conclusion: The resubmission process is a time-consuming and often frustrating experience for researchers. Our review identified opportunities to streamline and improve the process to enhance the biomedical research landscape., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: By 2030, an estimated 42% of the world's adolescent girls and young women (AGYW) will live in sub-Saharan Africa (SSA), where a quarter of AGYW pregnancies are undesired and AGYW represent 75% of new HIV infections. Most AGYW in SSA use short-acting contraceptive methods, including many who rely solely on condoms, which results in variable patterns of protection against undesired pregnancies and HIV. Dynamics of contraceptive use and HIV prevention efforts are poorly understood but the DYnamics of Contraception in Eswatini study will contribute to the understanding of the complex relationship between sexual behaviours, risk perception and HIV and pregnancy prevention., Methods and Analysis: All AGYW 18-24 years who participated in a 2021 nationally representative, population-based (face-to-face) HIV survey, consented to future research and provided a mobile phone number will be contacted for enrolment. Consenting AGYW will complete a baseline questionnaire and be surveyed biweekly for 2 years. The three objectives of the study are to (1) investigate how changing individual context (schooling, income, residential mobility) impact contraceptive use; (2) examine the relationship between pregnancy desires and contraceptive use and (3) test whether changes in a woman's perception of her HIV risk changes her probability of contraceptive use and HIV protective behaviours. Data collection will take place from March 2024 to March 2026 via computer-assisted telephone interviews. During recruitment (March-April 2024), two interviewers called 794 AGYW, of whom 326 completed the baseline questionnaire (41%) and 321 consented to biweekly follow-up (40% American Association for Public Opinion Research response rate #1). Analyses will mainly use hybrid within-between logistic regression models., Ethics and Dissemination: This protocol was reviewed and approved by the Eswatini National Health Research Review Board in 2024 and Columbia University Medical Center Institutional Review Board in 2023. Findings from the study will inform the Eswatini Ministry of Health approaches to mitigating undesired pregnancies and HIV among AGYW. Second, few examples exist of high-frequency longitudinal data collection in SSA, and this study will contribute to the survey method knowledge. Finally, the rich dataset will available for secondary data analysis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Globally, long-distance truck drivers' (LDTDs) risk of exposure to HIV infections is higher compared with other populations in transit. Thus, several HIV prevention interventions have been implemented, though to a narrower extent compared with other most at-risk populations. Consequently, the effectiveness of such interventions is not well understood. Therefore, a review is warranted to inform policymakers on the most effective HIV prevention interventions targeted for LDTDs., Methods and Analysis: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines were followed. Original peer-reviewed interventional studies involving LDTDs of either gender aged above 18 years, and reporting findings on HIV prevention interventions from any part of the world will be included. Non-empirical research studies like systematic reviews, literature reviews and scoping reviews will be excluded. A comprehensive search will be done from PubMed, Cumulated Index to Nursing and Allied Health Literature and other five databases to identify eligible studies. The Rayyan online platform will be used for the screening of titles and abstracts. For the meta-analysis, a random-effects meta-analysis using the ' metafor ' package in R software will be done. Where specific studies may not report adequate data for meta-analysis, their findings will be presented qualitatively. The Cochrane Collaboration tool and Joanna Brigs Checklist will be used to assess the quality and risk of bias in the included studies., Ethics and Dissemination: A formal ethical approval is not required for this systematic review and meta-analysis. The findings will be presented at scientific conferences and published in open-access peer-reviewed journals to reach policymakers, stakeholders and the scientific community., Prospero Registration Number: CRD42024505542., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Climate change is a paramount global health threat with multifaceted implications. Societal change is required to mitigate the negative effects of climate change, as well as help people adapt to the associated health risks. This requires situation-specific, large-scale data to help scientists and policymakers understand public perceptions and behaviours and identify the levers to increase public readiness to act against climate change and protect health. The Planetary Health Action Survey (PACE) assesses this readiness to act as a regular monitoring of representative samples in Germany. The ongoing monitoring seeks to develop and refine an integrated conceptual model of the trait-like readiness to act, comprising policy acceptance, political participation and individual behaviours as indicators of the trait. It also proposes as set of determinants to explain different levels of readiness to act. This study protocol provides newly developed valid measurement instruments and the methodological details of the monitoring., Method and Analysis: PACE assesses indicators of the readiness to act and a set of sociocognitive factors predicting the readiness to act in continuous cross-sectional data collections. The latter comprise climate change knowledge, trust in institutions, perceived health risks, self-efficacy, social norms and perceived effectiveness of policy measures. The online questionnaire is updated regularly. Data collection involves non-probabilistic quota samples from Germany (n≈1000 at each collection)., Ethics and Dissemination: The project adheres to the ethical guidelines of the University of Erfurt and the German Research Foundation. Ethical clearance was granted by the University's Institutional Review Board (No #20220525/No #2024-01). Participants are guaranteed confidentiality and anonymity, and informed consent is obtained before participation. Results will be published in peer-reviewed journals. Additionally, we aim to inform and empower the public and support stakeholders (media, policymakers, climate protection organisations) in preparing climate communication and assisting policymakers through the project website including an interactive tool, detailed reports and short summaries for practitioners., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Personalised medicine (PM) research programmes represent the modern paradigm of complex cross-disciplinary research, integrating innovative methodologies and technologies. Methodological research is required to ensure that these programmes generate robust and reproducible evidence. The PERMIT project developed methodological recommendations for each stage of the PM research pipeline. A common methodology was applied to develop the recommendations in collaboration with relevant stakeholders. Each stage was addressed by a dedicated working group, specializing in the subject matter. A series of scoping reviews that mapped the methods used in PM research and a gap analysis were followed by working sessions and workshops where field experts analyzed the gaps and developed recommendations. Through collaborative writing and consensus building exercises, the final recommendations were defined. They provide guidance for the design, implementation and evaluation of PM research, from patient and omics data collection and sample size calculation to the selection of the most appropriate stratification approach, including machine learning modeling, the development and application of reliable preclinical models, and the selection and implementation of the most appropriate clinical trial design. The dissemination and implementation of these recommendations by all stakeholders can improve the quality of PM research, enhance the robustness of evidence, and improve patient care., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: The objective of this study was to establish a zone of clinical equipoise for the Proximal FEmur Resection or Internal Fixation fOR Metastases (PERFORM) randomized controlled trial, which will compare resection and endoprosthetic reconstruction to internal fixation for skeletal metastases of the proximal femur., Methods: A survey was developed, piloted, and distributed to self-declared interested stakeholders in the PERFORM trial. The survey targeted orthopedic oncologists and was designed to assess patient and bone lesion characteristics that drive surgical decision-making in the treatment of skeletal metastases in the proximal femur. An Ethics Waiver was obtained at the lead academic institution and data was collected in the REDCap survey database., Results: Responses were complete from 76 surgeons across North America, South America, Europe, Asia, and Africa. Response rate from self-declared interested stakeholders was 70%, with additional responses collected from a broader international audience. Responses indicate that a study population for which either resection and endoprosthetic reconstruction or internal fixation are acceptable options include (1) life expectancy at least 6 months, (2) bone loss of no more than 75% and no less than 25%, and (3) minimal to moderate risk for perioperative complications. Ninety-three percent of respondents indicated that they would be interested in participating in the PERFORM trial., Conclusion: A preliminary zone of equipoise for the PERFORM trial includes patients with 25-75% bone loss, low to moderate risk of operative complications, and life expectancy of at least 6 months. Further stakeholder discussions have finalized the PERFORM trial protocol prior to study initiation., Competing Interests: Ethics approval and consent to participate An Ethics Waiver for this study was obtained at the lead academic institution. Consent for participation was inferred by survey completion. Consent for publication Consent for publication of survey data was inferred by survey completion. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Introduction: Micropapillary serous borderline ovarian tumours (MP-SBOTs) are an aggressive subtype of serous borderline ovarian tumours (SBOTs). Surgery is the mainstay of treatment. Radical surgery (RS, including debulking) is an alternative. However, for patients who are of reproductive age, another treatment option is fertility-sparing surgery (FSS). Up to now, the best surgical approach for MP-SBOTs and whether different procedures will have an impact on postoperative recurrence are still up for debate. This protocol outlines a systematic review and meta-analysis to investigate whether FSS adversely affected outcomes compared with RS in patients with MP-SBOTs. Additionally, we will do a prognosis analysis of BOTs with no microcapillary pattern and MP-SOBTs, if possible., Methods and Analysis: This protocol will consider non-randomised studies comparing outcomes in patients with MP-SBOTs treated with RS or FSS. The following databases will be searched: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, MEDLINE, Embase Medline, PubMed, Web of Science, China Biological Medicine Database, China National Knowledge Infrastructure and Wan Fang database. We will try our best to search the grey literature to avoid missing crucial research. Data collection and extraction will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of Bias in Non-randomised Studies of intervention will be used to assess non-randomized studies. We will assess the certainty of the evidence using the GRADEpro methodology and describe the degree of certainty of our results using suggested wording based on the GRADEpro assessment. We will conduct a meta-analysis and offer summary statistics for each result if there is enough data available. Instead, we will report the findings narratively where the data do not permit a statistical assessment., Ethics and Dissemination: Ethics approval was not required for this study. Results will be published through a peer-reviewed publication and communicated at scientific events once complete., Prospero Registration Number: CRD42023439136., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Emotion dysregulation is a transdiagnostic characteristic that affects many people with many psychopathological problems. Two mechanisms that have been frequently associated with emotional regulation are immersion and distancing. Focusing is a task that combines these two mechanisms of emotion regulation through the phase of creating a working distance and subsequently the phase of reassigning meaning. However, the benefit of its use in Portuguese population without a moderate to severe symptomatology for promoting mental health remains unclear., Methods and Analysis: Participants aged between 18 and 65 years who wish to improve their awareness and understanding of their emotions will be recruited and then, randomised into two groups: the intervention group (IG) and the control group (CG; delayed intervention). The IG will have access to two focusing sessions and the CG will only have access to the intervention 4 weeks later. Both groups will be evaluated at five different times. Primary outcomes include positive and negative affect, attitudes towards focusing (emotions and bodily sensations), the ability to perform focusing and emotion regulation. Secondary outcomes include mental health and psychological well-being, depression and anxiety symptoms and self-esteem., Ethics and Dissemination: Our study has been approved by the Council of Ethics and Deontology of the University of Maia. Findings will be disseminated via manuscripts, presentations and the lead author's thesis., Trial Registration Number: ISRCTN16974329., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: For several years, studies have been conducted on the contribution of social robots as an intervention tool for children with autism spectrum disorder (ASD). One of the early intervention models recommended by the French National Authority for Health is the Early Start Denver Model, an individualised, intensive programme based on play activities chosen by the child. While studies published in recent years suggest that robots provide benefits for autistic children in learning social interactions within a clinical setting, there is no scientific consensus on the widespread contribution and maintenance of their effects over time. On the other hand, a robotic solution controlled directly by a practitioner (ie, on-site telepresence system) enables greater adaptability to children's responses and choices during interventions. We believe that such a solution would enable better assessment of progress in the fundamental skills of expressive communication and imitation as well as greater engagement during interventions., Methods and Analysis: This is a prospective, monocentric, descriptive and evaluative pilot study based on single-case experimental design (SCED) methodology. The study will recruit eight children diagnosed with ASD aged between 2 and 5 years. The intervention will take place 15 min after the usual weekly care. The SCED methodology is constructed in three stages: (A) 4 weekly sessions at baseline without the robot, (B) 9 weekly sessions with intervention modification using a social robot as cotherapist and (C) 4 weekly sessions without the robot for follow-up., Ethics and Dissemination: Ethical approval was obtained from the South East IV Ethics Committee (CPP Sud-Est IV) (number: 2023-A00895-40) in France. Explicit consent is required from all legal representatives (parents) of children participating in this study. We aim to disseminate the results of this study through national and international conferences, international peer-reviewed journals and social media., Trial Registration Number: NCT05991791., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Olfactory dysfunction (OD) is a prevalent nasal affliction that has detrimental effects on the patients' quality of life and safety. Conventional therapeutic strategies have various limitations such as high costs, prolonged treatment durations and adverse side effects. Intranasal insulin is a novel intervention for the management of OD. To date, few systematic reviews have been conducted to evaluate the efficacy of this intervention. This study aims to critically assess the therapeutic efficacy and safety profile of intranasal insulin administration in patients with OD., Methods and Analysis: A systematic literature search will be performed on several databases, including PubMed, the Cochrane Central Register of Controlled Trials, Embase, SinoMed and China National Knowledge Infrastructure (CNKI), to identify studies investigating the efficacy of intranasal insulin in treating OD. The search will span from database inception to 1 April 2024, including publication in Chinese and English languages. Data will be retrieved from the literature by two independent investigators. Subsequently, the data will be processed using RevMan V.5.3.5. The meta-analysis will be performed in line with the Cochrane Handbook guidelines. The clinical efficacy and safety of intranasal insulin for OD will be appraised based on various outcomes, including overall symptom improvement, the Connecticut Chemosensory Clinical Research Center score, variations in serum glucose levels, body mass index variations and the incidence of adverse events., Ethics and Dissemination: This will be a systematic review of available literature; thus, no ethical clearance is required. The results of this study will be shared through journal publication or presented at an academic conference., Trial Registration Number: According to the guidelines, our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 16 May 2024 (registration number CRD42024543438)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Key informant interviews (KII) are a widely used method in qualitative health research to gain in-depth insights from individuals with specialized knowledge, experience, or access that is crucial to the research topic. However, there is growing criticism regarding how the selection of key informants is insufficiently described in research. This opacity is problematic as the authority and knowledge of key informants may be given undue weight in research findings, potentially overshadowing other non-expert samples. The resulting imbalance in representation can lead to favoring certain viewpoints while marginalizing others, and thereby reinforcing existing inequities., Methods: Using our KII study as an example, we demonstrate how we initially composed an ideal sample based on theoretical considerations and subsequently operationalized it in the field. We employed a selective recruitment strategy informed by intersectional theory, targeting physicians with migration backgrounds from Middle Eastern countries for a study on cancer prevention and screening. Our recruitment process combined direct methods, including database searches and email outreach, with indirect methods like snowball sampling and engagement with multipliers. The recruitment strategy was iterative, allowing for ongoing assessment and adaptation to ensure a diverse and representative sample., Results: The KII study successfully recruited 21 physicians with diverse social categories, including different genders, migration backgrounds, language skills, and medical specialties. Direct recruitment was more effective than indirect methods and allowed for greater control in reaching out to specific subsamples. It highlights the importance of flexible and persistent recruitment strategies to achieve the desired sample., Conclusions: This KII study underscores the interplay between methodological ideals and the practical realities of recruiting a diverse, carefully composed sample of key informants in health research. Our intersectional approach aimed to ensure equitable representation by considering power dynamics and refining recruitment strategies, while balancing the challenges of real-world fieldwork-such as engaging busy physicians with specific recruitment criteria-with practical adaptability. Our KII study emphasizes the need for ongoing reflexivity to balance ideality and equity with practical feasibility., Competing Interests: Declarations Ethics approval and consent to participate The research project was granted ethical clearance by the ethical board of Bielefeld University (No. 2022 − 181). Prospective participants from all samples received an information sheet, detailing their role, rights, type of data collection, data protection, and a consent form. Informed consent was obtained from all research participants. Invitations to attend any of the study components were extended to participants solely upon receipt of their signed consent forms. All our procedures have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Clinical trial number Not applicable. Consent for publication Written consent for publication was obtained from all study participants. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Premature birth is the leading cause of neonatal mortality. Cervical length shortening during pregnancy serves as the gold standard for predicting preterm birth. Although several interventions have been applied to reduce the incidence of preterm birth in short cervix pregnant women, the optimal intervention in clinical practice remains controversial. The aim of this study is to conduct a network meta-analysis to explore the optimal intervention for preventing preterm birth among pregnant women with a short cervix., Methods and Analysis: We will search electronic information databases including PubMed, Embase Ovid, Cochrane Library Ovid, Wanfang Data, China Science and Technology Journal Database(VIP) and clinical trial registry websites (US Clinical Trials Registry and China Clinical Trials Registry) until 1 January 2024. Randomised controlled trials (RCTs) comparing two or more interventions to prevent preterm birth in short cervix pregnant women will be included. The primary outcomes are preterm birth rate at <37 weeks and the composite neonatal adverse outcome, secondary outcomes include spontaneous preterm birth rate at <37 weeks, preterm birth rate at <34 weeks, spontaneous preterm birth rate at <34 weeks, week of gestation, birth weight of the newborn, perinatal mortality and neonatal admission rate. Risk of bias 2.0 (ROB 2.0） will be used to assess the risk of bias in the RCT, and the Confidence in Network Meta-Analysis software will be used to assess the certainty of the generated evidence. The network meta-analysis will be conducted using the gemtc package in R 4.2.2. Two investigators independently performed article screening, data extraction and quality assessment. In addition, subgroup analyses and sensitivity analyses will be used to assess the robustness of the findings., Ethics and Dissemination: Ethical considerations will not be required. Results will be published in a peer-review journal., Prospero Registration Number: CRD42022315200., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Individualized genetic therapies-medicines that precisely target a genetic variant that may only be found in a small number of individuals, as few as only one-offer promise for addressing unmet needs in genetic disease, but present unique challenges for trial design. By nature these new individualized medicines require testing in individualized N-of-1 trials. Here, we provide a framework for maintaining scientific rigor in N-of-1 trials. Building upon best practices from traditional clinical trial design, recent guidance from the United States Food and Drug Administration, and our own clinical research experience, we suggest key considerations including comprehensive baseline natural history, selection of appropriate clinical outcome assessments (COAs) individualized to the patient genotype-phenotype for safety and efficacy assessment over time, and specific statistical considerations. Standardization of N-of-1 trial designs in this fashion will maximize efficient learning from this next generation of targeted individualized therapeutics., Competing Interests: Competing interests Joseph Gleeson serves as a consultant for Ionis Pharmaceuticals, Neurocrine Pharmaceuticals, and the n-Lorem Foundation. Winston Yan is a founder, employee, and shareholder of Arbor Biotechnologies, and serves as President and Board Member of the N=1 Collaborative. Timothy Yu has received research support from EveryONE Medicines, and volunteer Board Member for the N=1 Collaborative, the Oligonucleotide Therapeutics Society, and the Society for RNA Therapeutics, and a volunteer advisor to several rare disease foundations. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Asthma exacerbations or 'attacks' can vary in severity from mild worsening of symptoms to life-threatening changes that require urgent hospital care. Understanding these exacerbations is crucial to improving treatment and support for patients. Electronic health records (EHR) using anonymised data from people with asthma in primary and secondary care can be used to understand exacerbations and outcomes. However, previous studies found significant heterogeneity in the algorithms used to define asthma exacerbations. Validating definitions of asthma exacerbations in EHR will lead to more robust and comparable evidence in future research., Methods and Analysis: Medline and Embase will be searched for the key concepts relating to asthma exacerbations, EHR and validation. All studies that validate exacerbations of asthma in EHR and administrative claims databases published before 30 May 2024 and written in English will be considered. Validated algorithms for asthma exacerbations or attacks must be compared against a reference or gold standard definition, and a measure of validity must be included. Articles will be screened for inclusion by two independent reviewers with any disagreements resolved by consensus or arbitration by a third reviewer. Study details will be extracted, and the risk of bias will be assessed using a QUADAS-2 tailored to this review., Ethics & Dissemination: No ethical approval is required as this is a review of previously published literature. Results will be disseminated in a peer-reviewed journal with the aim of being used in future research to help identify asthma exacerbation in EHR., Prospero Registration Number: CRD42024545081., Competing Interests: Competing interests: The author JKQ has been supported by institutional research grants from the Medical Research Council, NIHR, Health Data Research, GSK, BI, AZ, Insmed and Sanofi and received personal fees for advisory board participation, consultancy or speaking fees from GlaxoSmithKline, Chiesi and AstraZeneca., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Post-intensive care syndrome (PICS) seriously affects the quality of life of intensive care unit (ICU) survivors, their ability to return to work and society and the quality of life of their families, increasing overall care costs and healthcare expenditures. ICU follow-up services have important potential to improve PICS. However, the best clinical practice model of ICU follow-up service has not been fully defined and its benefits for ICU survivors are not clear. This review will synthesise and map the current types of follow-up services for ICU survivors and summarise the impact of follow-up services on PICS., Methods and Analysis: This scoping review will be conducted by applying the five-stage protocol proposed by Arksey and O'Malley in an updated version of the Joanna Briggs Institute. Eight academic databases including the Cochrane Library, MEDLINE, Web of Science, Embase, EBSCO Academic, CINAHL, PsycInfo and SinoMed (China Biology Medicine) will be systematically searched from inception to the present. Peer-reviewed literature and grey literature will be included. Qualitative, quantitative and mixed methods studies will be included. Studies published in English or Chinese will be included. There will be no time restriction. Two reviewers will screen and select the articles independently and if there is any disagreement, the two reviewers will discuss or invite a third reviewer to make decisions together. Descriptive analysis will be used to conduct an overview of the literature. The results will be presented in a descriptive format in response to the review questions accompanied by the necessary tables or charts., Ethics and Dissemination: Ethical approval is not required for this scoping review because data could be obtained by reviewing published primary study results and do not involve human participants. Findings should be disseminated at scientific meetings and published in peer-reviewed journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Target trial emulation is an approach that is increasingly used to improve transparency in observational studies and help mitigate biases. For studies declaring that they emulated a target trial, we aimed to evaluate the specification of the target trial, examine its consistency with the observational emulation and assess the risk of bias in the observational analysis., Design: Methodological systematic review reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement., Data Sources: The database MEDLINE (Medical Literature Analysis and Retrieval System Online) was interrogated for all studies published from 1 January 2021 to 3 July 2022. We performed an additional manual search of 20 general medical and specialised journals that spanned the same period., Eligibility Criteria: All studies that declared emulating a hypothetical or real randomised trial were eligible., Data Extraction and Synthesis: Two independent reviewers performed the whole systematic review process (screening and selection of studies, data extraction and risk of bias assessment). The main outcomes were the definition of the key protocol components of the target trial and its emulation, consistency between the target trial and its emulation and risk of bias according to the ROBINS-I (Risk Of Bias In Non-randomised Studies - of Interventions) tool., Results: Among the selected sample of 100 studies, 24 (24%) did not specify the target trial. Only 40 studies (40%) provided detailed information on all components of the target trial protocol. Eligibility criteria, intervention strategies and outcomes were consistent between the target trial and its emulation in 35 studies (46% of those specifying the target trial). Overall, 28 studies (28%) exhibited serious risk of bias and 41 (41%) had misalignments in the timing of eligibility assessment, treatment assignment and the start of follow-up (time-zero). As compared with studies that did not specify the target trial, those that did specify the trial less frequently seemed to have both time-zero issues (39% vs 52%) and serious risk of bias (26% vs 33%)., Conclusions: One-quarter of studies declaring that they emulated a target trial did not specify the trial. Target trials and their emulations were particularly inconsistent for studies emulating a real randomised trial. Risk of methodological issues seemed lower in observational analyses that specified versus did not specify the target trial., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare that they have no competing interest related to the study. GLM declares consulting fees from Synapse Medicine, unrelated to the study., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Traumatic brain injury (TBI) is one of the prevalent critical illnesses encountered in clinical practice, often resulting in a spectrum of consciousness disorders among survivors. Prolonged states of impaired consciousness can significantly elevate the susceptibility to complications such as urinary tract infections and pulmonary issues, consequently leading to a compromised prognosis and substantially impacting the quality of life for affected individuals. Clinical studies have reported that median nerve electrical stimulation (MNES) may have a therapeutic effect in the treatment of disorders of consciousness (DOC). We plan to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of MNES in the management of DOC subsequent to TBI., Methods and Analysis: We will conduct a comprehensive literature search in the following electronic databases: Web of Science, Embase, PubMed, Cochrane Library, China Biology Medicine, China National Knowledge Infrastructure, Wan Fang Database and Chinese Scientific Journal Database. The search will be performed from the inception of the databases until 30 September 2024. Furthermore, we will search for relevant ongoing trials in the International Clinical Trial Registry Platform, ClinicalTrials.gov and China Clinical Trial Registry. Grey literature will also be sourced from reputable sources like GreyNet International, Open Grey and Google Scholar. We will include eligible randomised controlled trials. The primary outcome of interest will be the assessment of consciousness disorder severity. To ensure rigour and consistency, two independent reviewers will screen the studies for inclusion, extract relevant data and assess the risk of bias. Any discrepancies will be resolved through discussion or consultation with a third reviewer. The quality of evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Data synthesis and meta-analysis will be conducted using STATA 15.1 software., Ethics and Dissemination: This systematic review and meta-analysis do not involve the collection or use of any individual patient data, thereby obviating the necessity for ethical review. The research findings will be disseminated through publication in peer-reviewed scientific journals., Prospero Registration Number: CRD42024533359., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The delayed and modest uptake of evidence-based treatments following cardiovascular clinical trials highlights the need for greater attention to implementation early in the development and testing of treatments. However, implementation science is not well understood and is often an afterthought following phase 3 trials. In this review, we describe the goals, frameworks, and methods of implementation science, along with common multilevel barriers and facilitators of implementation. We propose that some of the approaches used for implementation well after a trial has ended can be incorporated into the design of phase 3 trials to foster early post-trial implementation. Approaches include, but are not limited to, engaging broad stakeholders including patients, clinicians, and decision-makers in trial advisory boards; using less restrictive eligibility criteria that ensure both internal validity and generalizability; having trial protocols reviewed by regulators; integrating trial execution with the health care system; evaluating and addressing barriers and facilitators to deployment of the intervention; and undertaking cost-effectiveness and cost utility analyses across jurisdictions. We provide case examples to highlight concepts and to guide end-of-trial implementation., Competing Interests: Funding Support and Author Disclosures CVCT meetings are supported by unrestricted educational grants with no allocation for speakers’ fees. Dr Van Spall has received grants from the Canadian Institutes of Health Research (CIHR) and the Heart and Stroke Foundation (HSF); has institution educational accounts with Boehringer Ingelheim and Novartis; has received consulting fees from the Baim Institute for Clinical Research; has trial committee roles with Medtronic, CardioVascular Research Foundation, and the Colorado Prevention Center Clinical Research; and has received travel and/or meeting attendance support from CVCT. Drs Desveaux, Finch, and Singh have received travel and/or meeting attendance support from CVCT. Dr Lewis has received royalties or licenses from Springer Publishing for Practical Implementation Science. Dr Venter has received Institutional grants from the Bill and Melinda Gates Foundation, SA Medical Research Council, National Institutes for Health, Unitaid, Foundation for Innovative New Diagnostics, Merck and the Children's Investment Fund Foundation, USAID, Merck, Johnson and Johnson, ViiV Healthcare, and Novo Nordisk; has received honoraria for educational events and advisory board participation from Gilead Sciences, ViiV Healthcare, Mylan/Viatris, Merck, Adcock-Ingram, Aspen, Abbott, Roche, Johnson and Johnson, Sanofi, Boehringer Ingelheim, Thermo-Fischer, and Virology Education; has received honorarium from the International National Institutes of Health HIV Data and Safety Monitoring Board; and has received drug donations from ViiV Healthcare, Merck, Johnson and Johnson, and Gilead Sciences for investigator-led clinical studies. Dr Zannad has received consulting fees from 89bio, Applied Therapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior Pharmaceuticals, Cellprothera, Cereno Scientific, CEVA, CVRx, Merck, Novartis, Novo Nordisk, Owkin, Pfizer, and Servier; has received honoraria for lectures from Bayer, Boehringer Ingelheim, CEVA, CVRx, Merck, and Novartis; has received fees for participation on a data safety monitoring board or advisory board from Acceleron/Merck; and has equity interests in G3 Pharmaceuticals, Cereno Pharmaceuticals, Cardiorenal, Eshmoun Clinical Research, and CVCT. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The views expressed in this paper are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Similarly, the views expressed in this paper by other authors are their personal views and may not be understood or quoted as being made on behalf of or reflecting the position of the organizations with which the authors are employed/affiliated., (Copyright © 2024 American College of Cardiology Foundation. All rights reserved.)

Background: Pragmatic randomized controlled trials are getting more interest to improve trials' external validity. This study aimed to assess how pragmatic the design of the self-labelled pragmatic randomised controlled trials in the manual therapy field is., Methods: We searched MEDLINE and the Cochrane Central Register of Controlled Trials for self-labelled pragmatic randomised controlled trials in the manual therapy field until January 2024 were included. Two independent reviewers collected and extracted data related to the intention of the trial, the rationale for the intervention, and specific features of the trial and performed an assessment using the PRECIS-2 tool., Results: Of 39 self-labelled pragmatic trials, the mean PRECIS-2 score was 3.5 (SD: 0.6). Choice of outcome measures, how the interventions were performed, the follow-up of the participants and how all the available data were included in the statistical analysis were the domains rated as most 'pragmatic'. Participants' eligibility, recruitment, and setting obtained lower scores. Less than 25% of the trials claimed that the aim was to investigate an intervention under real-world conditions and to make clinical decisions about its effectiveness. In the 21% of the sample the authors described neither the proof-of-concept of the intervention nor the state of previous studies addressing related research questions., Conclusions: Self-labelled pragmatic randomised controlled trials showed a moderately pragmatic attitude. Beyond the label 'pragmatic', the description of the intention of the trial and the context of every PRECIS-2 domain is crucial to understanding the real pragmatism of a trial., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Family caregivers of people with dementia are a distinct group due to the particularly stressful and time-intensive care situation at home. Despite these challenges, involving them in research is crucial to better understand and address their specific needs. However, little evidence exists regarding a tailored approach for researchers for this group considering their situation at home., Methods: A scoping review will be conducted following the Joanna Briggs Institute methodological guidance, including the databases MEDLINE (PubMed), CINAHL, Scopus (Elsevier), and PsycINFO (EBSCO). The review will include family caregivers of people with dementia, regardless of age, gender, or ethnicity, who have been actively involved in research throughout the research process. Moreover, sources of evidence from any country in both English and German are eligible for inclusion. Sources will be screened by two independent reviewers. Results will be extracted using a tailored charting tool and presented in the final report according to the research questions and objectives., Discussion: Developing a tailored approach to involve family caregivers of people with dementia in research and development has profound importance to both the scientific community and the target group itself., Systematic Review Registration: Open Science Framework https://doi.org/10.17605/OSF.IO/PMZYV ., Competing Interests: Declarations Ethics approval and consent to participate N.A. Consent for publication N.A. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Introduction: Inclisiran, an siRNA targeting hepatic PCSK9 mRNA, administered twice-yearly (after initial and 3-month doses), substantially and sustainably reduced LDL-cholesterol (LDL-C) in Phase III trials. Whether lowering LDL-C with inclisiran translates into a reduced risk of major adverse cardiovascular events (MACE) is not yet established. In-silico trials applying a disease computational model to virtual patients receiving new treatments allow to emulate large scale long-term clinical trials. The SIRIUS in-silico trial programme aims to predict the efficacy of inclisiran on CV events in individuals with established atherosclerotic cardiovascular disease (ASCVD)., Methods and Results: A knowledge-based mechanistic model of ASCVD was built, calibrated, and validated to conduct the SIRIUS programme (NCT05974345) aiming to predict the effect of inclisiran on CV outcomes. The SIRIUS Virtual Population included patients with established ASCVD (previous myocardial infarction (MI), previous ischemic stroke (IS), previous symptomatic lower limb peripheral arterial disease (PAD) defined as either intermittent claudication with ankle-brachial index <0.85, prior peripheral arterial revascularization procedure, or vascular amputation) and fasting LDL-C ≥ 70 mg/dL, despite stable (≥4 weeks) well-tolerated lipid-lowering therapies.SIRIUS is an in-silico multi-arm trial programme. It follows an idealized crossover design where each virtual patient is its own control, comparing inclisiran to (i) placebo as adjunct to high-intensity statin therapy with or without ezetimibe, (ii) ezetimibe as adjunct to high-intensity statin therapy, (iii) evolocumab as adjunct to high-intensity statin therapy and ezetimibe.The co-primary efficacy outcomes are based on the time to the first occurrence of any component of 3P-MACE (composite of CV death, nonfatal MI, or nonfatal IS) and time to occurrence of CV death over 5 years., Perspectives/conclusion: The SIRIUS in-silico trial programme will provide early insights regarding potential effect of inclisiran on MACE in ASCVD patients, several years before the availability of the results from ongoing CV outcomes trials (ORION-4 and VICTORION-2-P)., Clinical Trial Registration: Clinicaltrials.gov identifier: NCT05974345., Competing Interests: Conflict of interest: Denis Angoulvant reports having received payment or honoraria for lectures, presentations, speakers bureaus or educational events from Amgen, Alnylam, Amarin, Astra Zeneca, Boehringer, BMS, Bouchara Recordati, Pfizer, Novartis, Novo Nordisk, Organon, Sanofi, Servier, Vifor. Gabriel Steg reports the following: research grants from Amarin and Sanofi. Consulting or speaking for Amarin, Amgen, BMS and Novo-Nordisk. Clinical Trials (Steering committee, CEC, DSMB) for Amarin, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Idorsia, Janssen, Novartis, Novo-Nordisk, Pfizer, Sanofi. Senior Associate Editor at Circulation and Chief Scientific Officer of Bioquantis Guillaume Mahé reports having received payments for consulting, speaking, or educational events from Amgen, Amarin, Bayer Healthcare, BMS, Leo Pharma, Novartis, Novo Nordisk, Pfizer and Sanofi. Bertrand Cariou reports having received payments for consulting, speaking, or educational events from Amgen, Astra Zeneca, BMS, Eli Lilly, Novartis, Novo Nordisk, Sanofi, Ultragenyx. Franck Boccara reports having received payments for consulting, speaking, or educational events from Amgen, Amarin, Novartis, Novo Nordisk, Boehringer, Servier, ViiV healthcare, Gilead and Sanofi. Pierre Amarenco reports the following: grants from the French government (PHRC: RIISC-THETIS, TST-40, SPICAF trials), Pfizer and AstraZeneca (TST trial). Speaker fee from Novartis, Viatris and Sanofi. Advisory board for Novartis and Neuraltide. Steering committee for Bayer., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Many individually randomized group treatment (IRGT) trials randomly assign individuals to study arms but deliver treatments via shared agents, such as therapists, surgeons, or trainers. Post-randomization interactions induce correlations in outcome measures between participants sharing the same agent. Agents can be nested in or crossed with trial arm, and participants may interact with a single agent or with multiple agents. These complications have led to ambiguity in choice of models but there have been no systematic efforts to identify appropriate analytic models for these study designs. To address this gap, we undertook a simulation study to examine the performance of candidate analytic models in the presence of complex clustering arising from multiple membership, single membership, and single agent settings, in both nested and crossed designs and for a continuous outcome. With nested designs, substantial type I error rate inflation was observed when analytic models did not account for multiple membership and when analytic model weights characterizing the association with multiple agents did not match the data generating mechanism. Conversely, analytic models for crossed designs generally maintained nominal type I error rates unless there was notable imbalance in the number of participants that interact with each agent., (© 2024 The Author(s). Statistics in Medicine published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Introduction: Gender is a well-established social determinant of health and health (in)equality. Gender-sensitive health indicators for health monitoring and health reporting can support gender mainstreaming in relevant policy areas and inform strategies to promote gender equality. They generally lack theoretical approaches to explain gender inequalities in health in the context of individual, social and structural circumstances. Gender-sensitive and intersectionality-informed health indicators provide a more accurate and nuanced picture of health outcomes and risks but are often lacking. The aim of this scoping review is to map the evidence on gender-sensitive and intersectionality-informed indicators for health reporting in order to support the development of an indicator set for German Federal Health Reporting., Methods and Analysis: This scoping review follows Arksey and O'Malley's methodological framework and its extension by Levac et al and will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. We will conduct a database search complemented by a backward citation search using English search terms to find research articles and grey literature (eg, reports, policy/working papers, book chapters) reporting on gender-sensitive health indicators in the context of health reporting in the European Union-27 and Organisation for Economic Cooperation and Development published since 2014. Electronic databases include Medline, PsycINFO, Embase, Scopus, CINAHL and Cochrane Library. Other resources include targeted searches on websites relevant to national and international health reporting and a Google Search to include further eligible literature. After removing duplicates, two reviewers will independently screen all titles/abstracts and full texts for eligibility for inclusion and extract the data from included articles using a data extraction form. The results will be synthesised both narratively and descriptively and, where appropriate, presented in tables and graphs., Ethics and Dissemination: No ethical approval is required for this study. Findings will be disseminated through peer-reviewed publication, conference presentations and meetings with relevant stakeholders in health monitoring and reporting., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)