Objective: To evaluate the association between non-steroidal anti-inflammatory drugs (NSAIDs) and miscarriage, which remains elusive in the actual literature, using modelling approaches to mitigate time-related bias.
Design: Nationwide, population-based retrospective cohort study.
Setting: The study used data from the French National Mother-Child Register (EPI-MERES), developed from the French National Health Data System containing the health information (hospital admissions, drug dispensing, comorbidities, etc.) of about 99% French population.
Participants: 4 857 907 pregnancies ended in a live birth, a stillbirth or a miscarriage from 2013 to 2019.
Interventions: Exposure to NSAIDs from 2 weeks before conception to the 20th week of pregnancy.
Main outcome measures: Miscarriage (ie, spontaneous abortion before the 20th week of pregnancy) from the sixth week of pregnancy. The Cox regression with a time-dependent exposure that incorporated a 3-day lag was used to estimate HRs and their 95% CIs adjusted for maternal characteristics. The 3-day lag period allows for addressing protopathic bias.
Results: In total, there were 163 666 (3,37%) miscarriage cases, and 349 294 (7.19%) pregnancies were exposed to NSAIDs. Unexposed pregnancies were used as the reference category in all analyses. In the main analysis, exposure to NSAIDs increased the risk of miscarriage (HR, 1.83; 95% CI 1.81 to 1.86). The effect of individual drugs was heterogeneous, with 7 of the 19 drugs evaluated shown to increase the risk (flurbiprofen had the highest risk (HR, 3.28; 95% CI 3.15 to 3.41) and naproxen the lowest (HR, 1.09; 95% CI 1.01 to 1.18)). In the sensitivity analyses, increasing the lag time decreased the estimated HR (from HR, 2.25; 95% CI 2.21 to 2.28 with no lag to HR, 1.56; 95% CI 1.54 to 1.59 with a 7-day lag). Overall, the risk of miscarriage remained statistically significant in all the analyses.
Conclusions: Our study found that early exposure to NSAIDs could increase the risk of miscarriage. This finding contributes to the body of evidence on their safety profile and may help inform future recommendations for their use in pregnant women.
Introduction: The 'strike early and strike strong' lipid-lowering strategy emphasises rapid reduction of low-density lipoprotein cholesterol (LDL-C) in patients with acute coronary syndrome (ACS). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are increasingly used alongside statins to achieve guideline-recommended LDL-C targets after ACS. However, despite substantial LDL-C reductions with early PCSK9i initiation, their effects on non-culprit coronary atherosclerotic plaques remain unclear. This study aims to assess the impact of early intensive LDL-C lowering with PCSK9i added to moderate-intensity statin therapy on optical coherence tomography (OCT)-derived plaque characteristics in non-culprit coronary lesions in patients with ACS.
Methods and analysis: In this prospective, multicentre, open-label trial, 212 patients with ACS will be randomised 1:1 to an early intensified lipid-lowering strategy (PCSK9i added to moderate-intensity statin) or guideline-directed medical therapy for 6 months. Serial OCT imaging of non-culprit coronary arteries with 20-70% stenosis will be performed at baseline and 6 months. The primary endpoint is the absolute change in minimum fibrous cap thickness within a matched target arterial segment from baseline to 6 months. Secondary endpoints include changes in minimum lumen area, maximum lipid arc, presence of macrophage infiltration, LDL-C reduction and achievement of LDL-C targets. The primary endpoint will be analysed using analysis of covariance, adjusting for treatment group, baseline LDL-C stratification (≥1.8 vs <1.8 mmol/L), and baseline minimum FCT. Secondary continuous outcomes will be analysed similarly, while categorical outcomes will be compared using chi-square, Fisher's exact test or logistic regression, as appropriate.
Ethics and dissemination: Ethics approval was granted by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University (2024 Review No 1943). Results will be disseminated via peer-reviewed publications and presentations at academic conferences.
Trial registration number: NCT06791031.
Introduction: Diagnostic stewardship is an emerging concept, so far primarily associated with microbiology, specifically antibiotic stewardship. However, its core idea, ensuring 'the right test at the right time for the right patient', holds relevance across all areas of clinical medicine. By optimising the diagnostic process, diagnostic stewardship aims to enhance clinical decision-making and promote more effective, efficient and patient-centred care. Key objectives are the reduction of diagnostic errors, namely overdiagnosis, underdiagnosis and misdiagnosis, as well as optimal resource management. The aim of our review was to establish whether and how diagnostic stewardship has been implemented outside the area of antibiotic stewardship.
Methods and analysis: This scoping review will be conducted in accordance with the Joanna Briggs Institute (JBI) guidelines and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) checklist. Medline, Embase, Web of Science, Scopus, Google Scholar and Proquest Thesis and Dissertation will be searched using a search strategy based on the population, concept, context (PCC) framework, adding an outcome variable. Studies will be screened by two independent reviewers and reported using the PRISMA flowchart. Included will be studies starting from 2015, which will describe stewardship interventions in different diagnostic modalities. Excluded will be results regarding antimicrobial stewardship. No language restriction will be applied. Information on the definition and application of the concept of diagnostic stewardship, as well as general study characteristics, will be extracted using a previously developed and piloted data extraction form. Extracted data will be analysed and reported using narrative and descriptive analysis.
Ethics and dissemination: Ethics approval is not required for this scoping review. Dissemination activities include peer-reviewed journal publication and conference presentations.
Introduction: Shift work is associated with disrupted sleep, circadian misalignment and increased risks of adverse health, performance and safety outcomes. Although recommendations for shift workers typically focus on obtaining one long sleep period, many shift workers divide sleep into two episodes, referred to as biphasic sleep. Biphasic sleep may help mitigate sleep loss-related impairments, yet its prevalence, characteristics and potential benefits for shift working populations remain unclear. Existing reviews have examined sleep duration, mental health, or the consequences of shift work broadly, but none have specifically mapped evidence comparing biphasic and monophasic sleep between shifts. This scoping review will identify and summarise the available literature on biphasic sleep among adult shift workers. In addition, we will describe the outcomes and subsequently highlight any possible gaps to inform future research.
Methods and analysis: This review will follow the Joanna Briggs Institute methodology for scoping reviews and be reported in accordance with the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews guidelines. Biphasic sleep is defined as two distinct sleep episodes within a 24-hour period between work shifts, including two similarly timed sleep periods or one longer sleep combined with a shorter nap. A comprehensive search will be conducted in April 2026 in MEDLINE, Embase, PsycINFO, Web of Science and CENTRAL using controlled vocabulary (eg, Medical Subject Headings) and free-text terms related to shift work and split sleep. Peer-reviewed primary research examining biphasic sleep among adult shift workers will be included, and studies focusing solely on naps during work hours will be excluded. Two reviewers will independently screen titles/abstracts and full texts, with discrepancies resolved through discussion or by consulting a third reviewer. Data will be extracted using a standardised template including study characteristics, sleep parameters and reported outcomes. Results will be summarised descriptively and presented in tables and evidence maps. No statistical synthesis will be performed.
Ethics and dissemination: This scoping review will synthesise data from articles published in peer-reviewed journals. As no primary data will be collected and no human participants will be involved, the review is exempted from formal ethical approval. Findings will be disseminated in terms of a peer-reviewed publication and will inform future systematic reviews on sleep strategies among shift workers.
Trial registration number: This project is registered with the Open Science Framework accessible at 10.17605/OSF.IO/WY7KJ.
Introduction: This multi-centre, randomised controlled trial (RCT) investigates the effects of intensive upper limb (UL) motor training on neurophysiological and functional recovery in individuals with cervical spinal cord injury (c-SCI) during the sub-acute phase. The study aims first to assess neurophysiological adaptations in the central and peripheral nervous systems and functional changes to evaluate the impact of intensive UL motor training on recovery. Second, it determines dose dimensions and their correlation with neural and functional improvements.
Methods and analysis: A total of 44 individuals with c-SCI within 13 weeks post-injury will be recruited from five rehabilitation centres in Belgium and the Netherlands. They will be randomised into an intervention group, receiving six additional hours of goal-directed UL training per week for 8 weeks, or a control group receiving standard care. Primary outcomes are changes in resting motor threshold, a proxy for corticospinal tract integrity; compound muscle action potential amplitude, indicating peripheral nerve excitability and functionality; and assessments of strength, sensory function and prehension, with the primary comparison between groups at baseline and after the intervention period. Secondary outcomes cover additional neurophysiological assessments and motor function. Dose dimensions will be quantified and related to primary and secondary outcomes.
Ethics and dissemination: The central medical ethics committees, METC Máxima MC (NL84212.015.23) and MEC Gent (B6702023000227), as well as local ethics committees, reviewed and approved this trial. The protocol is registered (ClinicalTrials.gov; NCT06065384). The findings of this RCT will be disseminated through articles in peer-reviewed journals and at neurological rehabilitation conferences.
Trial registration number: NCT06065384.
Introduction: Administration of antibiotics before incising the skin ('surgical antimicrobial prophylaxis') is a critical infection prevention strategy in surgery. Extending doses of prophylaxis into the postoperative period is a common practice in cardiac surgery; however, the benefit has not been clearly established and may lead to emergence of antimicrobial resistance and patient harm. We present the protocol for a large international multicentre, adaptive, pragmatic, double-blind, three-arm, placebo-controlled, randomised, non-inferiority clinical trial to compare the incidence of surgical site infection after three different durations of postoperative surgical antimicrobial prophylaxis in patients undergoing cardiac surgery.
Methods and analysis: This adaptive, multi-arm multistage non-inferiority trial will compare intraoperative only (Arm A), to intraoperative and 24 hours (Arm B) and, to intraoperative and 48 hours (Arm C) of intravenous cefazolin and placebo as surgical antimicrobial prophylaxis in 9180 patients undergoing cardiac surgery. The adaptive design allows for potential dropping of any of the three arms if clear inferiority is indicated at any of the scheduled interim analyses. The trial will evaluate the clinical and cost-effectiveness of the three different antibiotic prophylaxis durations.
Ethics and dissemination: Ethics approval will be obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences. Patients and members of the public will also be involved in the dissemination and translation of the trial results.
Trial registration number: NCT05447559.
Background: While almost half of older adults admitted to hospital are prescribed potentially inappropriate medicines, less than 1% have a medicine proactively deprescribed during admission in the UK. The CompreHensive geriAtRician-led MEdication Review (CHARMER) intervention is designed to address geriatricians' and pharmacists' barriers and enablers to deprescribing. The CHARMER definitive trial will evaluate effectiveness, cost-effectiveness and safety.
Methods: A stepped-wedge cluster randomised controlled trial will be conducted in 20 hospitals in England, with four hospitals in reserve. All hospitals will collect baseline data. Every 3 months, five hospitals will be randomised to receive the intervention. The intervention, implemented by a local project manager, comprises a hospital action plan to set deprescribing as an organisational goal; workshops for pharmacists and geriatricians to change beliefs about deprescribing; weekly briefings between geriatricians and pharmacists to discuss opportunities for deprescribing; benchmarking reports to compare deprescribing performance across participating hospitals. With an average of 200 patients admitted and discharged during each step, the study will have 89.5% power at 5% significance level and intra-class correlation coefficient of 0.05 to detect a 3% difference in 90-day re-admission rate from 16.7% versus 13.7%. Anonymised routinely collected data, including readmissions, will be obtained for all patients admitted during the study period. Enhanced data collection periods of 1 month during control and intervention periods will be used to recruit patients and data for secondary outcomes and process evaluation.
Discussion: A stepped-wedge design enabled a smaller number of hospitals and patients to be included than a traditional cluster-randomised design. The complexity of intervention implementation necessitated a project manager in addition to the principal investigator responsible for trial conduct. Using routinely collected data for the primary outcome measure should ensure that the trial has sufficient power on completion. Planned enhanced data collection for short periods of time improves trial efficiency.
Trial registration number: ISRCTN13248281.
Objective: The aim of this study is to explore in depth adolescents' insights regarding experiences of spectacle lens wear and its correlation with self-perception, quality of life, social interactions, adherence and barriers.
Design: Qualitative design through individual interviews and thematic analysis.
Setting: Middle school students in five regions of Jakarta Province.
Participants: 31 middle school adolescents who participated and received free spectacle wear by the Indonesian Ophthalmologist Association.
Methods: A set of semistructured questionnaires exploring adolescents' perception regarding spectacle lens wear, adapted from the PedEyeQ. Interviews were conducted on site or through Zoom and were then transcribed.
Findings: Thematic analysis identified three themes, as follows: (1) experience with eyeglasses, (2) motivation and encouragement and (3) barriers to usage. This study found that more than half of adolescents received their first spectacles during the outreach programme, with most reporting improved vision and academic performance after spectacle wear. However, adherence varied, as some participants-particularly those with moderate to high myopia and astigmatism-did not use their new glasses due to discomfort, poor fit or dissatisfaction with visual clarity. While initial adaptation often involved dizziness or soreness, most adjusted within a week. The majority recognised the importance of spectacle wear, describing clearer vision, reduced eye strain and improved confidence, though a minority viewed it as unnecessary. Parents played a central role in influencing health-seeking behaviour, and limited prior access to eye examinations and geographic challenges restricted care for several adolescents. Financial concerns were reported by a small proportion, while psychological barriers such as fear of teasing or negative self-perception were the major barrier. Overall, adolescents highlighted both the benefits and challenges of spectacle wear, with motivation shaped by personal experience, parental influence and accessibility of eye care services.
Conclusions: Findings showed insight that adolescent understanding regarding eye health is imperative to support adherence. However, psychological barriers act as a major factor that impedes lens wear. Involving parents and teachers in understanding urgency and severity of eye health in adolescents, specifically refractive error and its long-term negative impact, as well as the prominent psychological barriers, may improve adolescent perception and adherence.
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