BMJ

Objectives To quantify the frequency of baseline control-group use in published long COVID prevalence studies and assess their key methodological features. Design Cross-sectional meta-epidemiological evaluation of published post-acute COVID-19 prevalence studies, supplemented by a corresponding-author survey. Setting Published studies identified through a systematic review by Hou et al. (2025) and supplementary data obtained through direct email contact with corresponding authors. Participants A total of 440 published long COVID prevalence studies. Main Outcome measures Presence and type of comparator group, reliance on solely self-reported outcomes, acknowledgment of lack of a control group among uncontrolled studies, and availability of additional comparator data through author survey. Results Among 440 studies, 372 (84.5%) reported no control group on their publication. Healthy or uninfected comparators were reported in 55 studies (12.5%) and other comparator types in 14 (3.2%); 1 study included both categories. Solely self-reported outcomes were used in 279 studies (63.4%). Among 372 uncontrolled studies, 244 (65.6%) did not explicitly acknowledge the absence of a baseline comparator as a limitation anywhere in text. Corresponding authors of 140 studies (31.8%) responded to the survey; among them, 126 (90.0%) reported no additional comparative data, while 14 (10.0%) mentioned some available comparative datasets (19 additional datasets). Almost all of that information (10/14, 17/19) had been already published in other articles not captured by the Hou et al. systematic review. Conclusions Most published long COVID prevalence studies lacked comparator groups and relied exclusively on self-reported outcomes without acknowledging this limitation. Direct author contact identified little additional comparator information. Much of the long COVID prevalence literature may therefore be poorly suited to estimating burden attributable specifically to SARS-CoV-2, underscoring the need for appropriately matched comparators and more objective outcome assessment. Registration The protocol was prospectively registered on the Open Science Framework (https://osf.io/f4hra).

Background and Aims SARS-CoV-2 infection is associated with an increased risk of cardiovascular, cerebrovascular and venous thromboembolism events. We aimed to assess the impact of COVID-19 vaccination prior to SARS-CoV-2 infection on the risk of these events post-infection. Methods Embase and MEDLINE were searched from January 2021 to 11 September 2025, supplemented by citation searching. Observational studies were included if they reported risks of cardiovascular, cerebrovascular, or venous thromboembolic events after SARS-CoV-2 infection between different vaccination groups (e.g. unvaccinated, vaccinated, or booster vaccinated), or reported risk of events after SARS-CoV-2 infection compared with no infection, stratified by vaccination status. Random-effects meta-analyses were conducted to estimate pooled hazard ratios (HRs) comparing vaccinated and unvaccinated individuals across prespecified outcomes. Results Twenty-three studies were included in the systematic review; most reported an association between vaccination and a reduced risk of post-infection vascular events. Ten studies were included across meta-analyses comparing vaccinated and unvaccinated individuals. Pre-infection vaccination was associated with significantly reduced risks of composite cardiovascular/cerebrovascular events (HR 0.60, 95% confidence intervals [CI] 0.51-0.69), stroke (HR 0.75, 95% CI 0.64-0.88), acute coronary syndrome (HR 0.70, 95% CI 0.52-0.95), arrhythmias (HR 0.82, 95% CI 0.69-0.98), and venous thromboembolism (HR 0.51, 95% CI 0.36-0.73). No statistically significant reduction was observed for heart failure (HR 0.72 [95% CI 0.47-1.10]). Conclusions Pre-infection COVID-19 vaccination is associated with lower risks of cardiovascular, cerebrovascular and venous thromboembolism events following SARS-CoV-2 infection in the pre- and post-Omicron eras, supporting its role within broader prevention strategies

BackgroundThe multicentre WOMAN trial showed that tranexamic acid reduces postpartum haemorrhage (PPH) deaths. Several studies have recommended adjusting for clustering at the country and centre level to improve power and reduce bias in the standard errors. We reanalysed data from the WOMAN trial, adjusting for these centre effects. MethodsThe WOMAN trial recruited 20,060 women with clinically diagnosed PPH from 193 centres in 21 countries. The intervention was intravenous tranexamic acid versus matching placebo and the outcome was death from bleeding within 42 days of randomisation. We reanalysed data for the 14,928 women treated within 3 hours of birth for whom tranexamic acid provided the most benefit. We used random effects logistic regression to calculate the effect of tranexamic acid taking into account variation in risk of death and treatment effectiveness by country and centre. We calculated intraclass correlations (ICCs) to quantify between country and between centre within country variation. Results216 (1.4%) women died from bleeding. Using a univariable analysis without adjusting for centre effects, we found tranexamic acid reduced the odds of death from bleeding by 31% (OR=0.69 95% CI: 0.52-0.90, p=0.007). Adjusting for baseline covariates (age, systolic blood pressure (SBP) and SBP2) but not country or centre yielded a 36% odds reduction (OR=0.64 95% CI: 0.48-0.85 p=0.002). Adjustment for baseline covariates, country and centre yielded a 37% odds reduction (OR=0.63 95% CI: 0.48-0.85 p=0.002). We found substantial between country and centre variation in outcomes but not treatment effectiveness. The ICC for outcome was 14% for country and 19% for centre within country. ConclusionsAdjusting for country and centre effects made negligible differences to the magnitude of the treatment effect estimate or its associated p-value. Consistent with other studies of large clinical trials for medicines with binary outcomes, we found considerable between country and centre variation in outcomes but not in relative treatment effectiveness. Despite substantial ICCs for the outcome, adjusting for country and centre effects had minimal impact on our results. Trial registrationclinicalTrials.gov:NCT00872469 (March 2009)

Background Planned caesarean birth (CB) is an increasingly utilised intervention, observed in almost 1 in 6 first-time mothers giving birth in the UK in 2023-24. Outcomes of planned (or actual) CB have been compared with planned (or actual) vaginal birth (VB) in a UK national guideline, but the scope of the comparison does not fully reflect the range of outcomes of interest to stakeholders. This review provides a comprehensive synthesis of outcomes of planned or actual CB with planned or actual VB to shape information resources which support informed birth planning. Methods The UK NICE Caesarean Birth Guideline NG192 evidence review of outcomes associated with planned CB (or actual CB where no planned CB data was available) was updated and expanded to incorporate additional outcomes prioritised by stakeholders. Results A total of 33 new study reports were combined with 32 reports previously included in NG192. All new reports were observational cohort studies or systematic reviews at low risk of bias. Only 3 studies reported outcomes of planned CB compared with planned VB (regardless of actual mode of birth), whereas all remaining studies reported actual VB outcomes. Planned CB was followed by more maternal infection (wound infection, mastitis, endometritis and urinary tract), venous thrombosis and lower neonatal unit admission rates than a planned VB. In the long-term, CB was linked to one or more sexual problems (insufficient lubrication and dyspareunia) being more common, future pregnancy being less common, and infertility being more frequent than after VB. For offspring, infant urinary tract infection after any CB, gastrointestinal tract infections and autism after planned CB were more common compared with VB. New findings highlight conflicting reports on childhood asthma and type 1 diabetes risk after planned CB, suggesting that prior positive associations may be explained by confounding. Existing evidence in NG192 suggests that cardiac arrest, maternal death and hysterectomy are more common after planned CB, but arise from studies at high risk of bias. NG192 also reports that placenta accreta and uterine rupture in a future pregnancy are more common after any CB. No new evidence was identified on these outcomes. Conclusion This review provides stakeholder-relevant information to populate decision-support materials on outcomes of planned (and actual) CB compared with planned (and actual) VB. The existing evidence base lacks data on long-term outcomes of planned (rather than actual) VB.

Title and abstract screening limit the timeliness of systematic reviews used for clinical guidelines. We evaluated audited large language model (LLM) triage at Sweden's National Board of Health and Welfare. Ten LLMs from five model families were tested on 419 Cochrane reviews comprising 26,892 records, and the selected ensemble was externally validated on 133 reviews including 8,501 records matched to planned guideline topics. The same locked model pair was then used prospectively across 24 systematic reviews in two national guideline programmes. On the 419-review selection benchmark, the selected Gemini-3-flash plus GPT-5.1 ensemble achieved 98.0% (95% CI, 97.3-98.7) mean review-level sensitivity, while topic-matched validation yielded 96.7% sensitivity (95% CI, 93.7-98.9). Prospective deployment screened 74,679 records, placed 63,858 (85.5%) in the AI-excluded pool and reduced estimated first-pass screening effort from 415 to 34 person-days. Across 600 randomly sampled AI-excluded records from the migraine and dementia programmes, none was confirmed as a final false negative after post-unblinding adjudication; across the completed 680-record audit, all 38 final retained records had been AI flagged, whereas locked blinded human consensus missed seven. These findings support locked, audited LLM triage, with human oversight and programme-specific monitoring, for systematic reviews used in national guidelines.

Background Home Test-to-Treat (HTTT) programs deliver timely antiviral treatment for acute respiratory infections, including COVID-19 and influenza, through at-home testing and telehealth. Because access is often measured by visit occurrence, variation in how and when care is delivered may be overlooked. We hypothesized that telehealth access follows distinct process-based patterns. Methods We analyzed de-identified encounters from the national HTTT program (September 2023-July 2024); 6,213 of 8,160 eligible individuals remained after exclusions for missing data. Phenotypes were derived by k-means clustering of standardized variables capturing encounter timing, modality preference, process duration, and sociodemographic and digital access attributes. Ten-day surveys assessed symptom duration and healthcare utilization. Results Three phenotypes emerged: Delayed/Disrupted Access (n = 1,537; 24.7%), Digitally Engaged but Socioeconomically Vulnerable (n = 1,460; 23.5%), and Mainstream Access and Efficient Utilization (n = 3,216; 51.8%). Mean process duration differed (15.93 [SD 3.84] vs 3.69 [3.31] vs 2.87 [2.41] hours; p < 0.001). Synchronous preference was lowest in the Digitally Engaged group (22.9%); antiviral prescribing was high (88.6%-91.9%). Among 10-day respondents (n = 1,023), symptom duration did not differ. Emergency department visits were most frequent in the Digitally Engaged group (2.3% vs 0.0% and 0.5%; p = 0.02) and urgent care in the Delayed/Disrupted group (5.8% vs 4.1% vs 2.0%; p = 0.02). Conclusions Telehealth use in a national HTTT program formed distinct phenotypes defined by timing, modality, and care-process efficiency. Evaluating equity requires attention to how and when care is delivered, not simply whether it occurred.

Background Thalassemia is one of the most common monogenic disorders worldwide, current screening strategies combining hematological testing with molecular assays still carry a risk of missed diagnoses and undesirable efficiency, particularly for complex structural variants and rare mutations. Methods In this prospective double-blind, multicenter cohort study of 3,842 participants (3,362 pregnant women and 480 male partners), we conducted a head-to-head comparison to systematically evaluate the incremental clinical value and detection performance of single-molecule nanopore sequencing in thalassemia (SMITH) against conventional hematological testing and next-generation sequencing (NGS). Findings The overall concordance rate between NGS and SMITH was 98.6% (3789/3842). The discrepant cases (n=53) were directly attributed to the superior detection capabilities of SMITH, which successfully identified complex structural rearrangements-including 45 -globin gene triplications and four HK alleles-that were missed by NGS. Furthermore, SMITH accurately detected four rare variants (c.134_135insT/, c.-22(C>T)/, {beta}N/{beta}c.316-290delinsAGGGCAATAATTT and {beta}3.5 kb deletion/{beta}N ) and resolved ten trans and three cis configurations within the globin gene allele. Clinically, these technical advantages translated to a 9.3% (5/54) increase in the detection rate of high-risk prenatal couples, effectively preventing one birth affected by moderate-to-severe thalassemia. Additionally, SMITH corrected a diagnostic discrepancy in one case (HK vs. -3.7), sparing the couple from an unnecessary invasive procedure. Interpretation Our findings demonstrate that SMITH provides a powerful platform for resolving globin gene rearrangements, detecting rare variants, and enabling direct haplotype phasing. By effectively eliminating diagnostic blind spots, SMITH is expected to become an optimal method for thalassemia prevention programs. Funding This study was supported by Chinese National Natural Science Foundation Projects 81760037 and 82271894.

Importance: Despite the benefits of statin therapy in individuals with diabetes, fewer than 70% of adults with diabetes meet contemporary guidelines for statin therapy and reducing low-density lipoprotein cholesterol (LDL) to <100 mg/dL. Evidence describing delays in statin initiation after diabetes diagnosis and associated clinical outcomes may motivate process of care interventions to improve guideline recommended care in individuals newly diagnosed with type 2 diabetes mellitus (T2D). Objective: To examine the timing of statin initiation and achievement of LDL <100 mg/dL after diabetes diagnosis, and to determine the association of early LDL reduction among statin initiators with incident atherosclerotic cardiovascular disease (ASCVD). Design: Retrospective observational cohort study using data from 2005-2021 Setting: Veterans Affairs Health Care System (VA) Participants: Individuals with newly diagnosed T2D Exposure: Primary exposure was ASCVD risk based on ACC/AHA Pooled Cohort Equations; secondary exposure was LDL <100 mg/dL in the first year after T2D diagnosis among statin initiators Main Outcomes and Measures: Co-primary outcomes were initiation of statin therapy and achievement of LDL <100 mg/dL within 5 years of diabetes diagnosis; incident 5-year ASCVD was a secondary outcome. Results: Among 100,406 individuals with newly diagnosed T2D, 59,615 were prescribed statin therapy within five years (59.4%), and 44,783 (57.5%) of those with LDL above goal achieved LDL <100 mg/dL within 5 years. Relative to those at low (<7.5%) 10-year ASCVD risk, individuals at intermediate (7.5-20%) and high (>20%) risk were more likely to be initiated on a statin (intermediate: Hazard Ratio [HR] 1.14 [95% CI 1.11, 1.17]; high: HR 1.16 [95% CI 1.13, 1.19]) and to achieve LDL <100 mg/dL (intermediate: HR 1.23 [95% CI 1.19, 1.26]; high: HR 1.34 [95% CI 1.30, 1.38]). Among those prescribed a statin within one year of diabetes diagnosis, achieving LDL <100 mg/dL in the first year after diabetes diagnosis was associated with lower risk of 5-year incident ASCVD (HR 0.84 [95% CI 0.77, 0.92]). Conclusions and Relevance: Gaps in guideline-directed primary prevention of ASCVD arise early following initial diabetes diagnosis. Guideline recommended early LDL lowering among statin initiators was associated with improved clinical outcomes.

Objectives: To evaluate if direct access to a Pregnancy Early Access Center (PEACE) improves the timeliness and efficiency of pregnancy loss care. Methods: We conducted a retrospective cohort study of patients diagnosed with EPL from January 2017 to December 2022 within a single healthcare system. We included EPL patients treated with procedural or medication management who had been assessed for a related early pregnancy complaint in the thirty days prior. The exposure was direct utilization of PEACE (yes/no) between first EPL symptom visit and EPL management. The primary outcome was "care latency" defined as days from initial presentation for concerning early pregnancy symptoms to initiation of active management. Secondary outcomes included "care continuity," the number of care teams encountered, "care efficiency," the number of patient encounters, and the type of EPL management received. Results: The evaluable cohort included 2151 individuals, with 36.5% patients of Black race and 30.3% publicly insured. A total of 885 (41.1%) received any EPL care at PEACE and 246 (11.4%) initiated their care at PEACE. Patients initiating care through PEACE experienced a 5-day reduction in care latency compared to patients who did not access PEACE. Adjusting for age, race, and insurance type, patients whose index EPL visit was with PEACE initiated their treatment twice as quickly as those who never saw PEACE (aHR 2.36 [95% CI, 2.05-2.71]). Care efficiency (median 2 [1-3] encounters) and care continuity (median 4.5 [4-7] care teams) were also improved by an index visit with PEACE when compared with controls (3 [2-4] and 6 [4-8] p<0.01), respectively). Conclusions: The Pregnancy Early Access Center (PEACE) model is associated with reduced care latency and improved efficiency and continuity when compared with routine care. PEACE reduces barriers to timely, patient-centered early pregnancy care.

Background During infectious disease outbreaks, characteristics of reported cases are routinely collected. These give information on becoming infected but not on infecting others. We assess whether linking infectees to infectors, together with their characteristics, can help understand transmission. Methods From the start of the COVID-19 pandemic in the Netherlands, reported cases were asked to identify their most probable infector in routine surveillance, enabling the linking of cases. We assess for the period 27 February 2020 - 11 April 2022 whether the infectees of these transmission pairs are representative of all reported cases, whether the transmission pairs yield verifiable estimates of epidemiological characteristics (here the serial interval), and whether they provide information on transmission that cannot be obtained otherwise. Results Of 8,003,008 reported cases, 678,482 (8.5%) could be linked to their most probable infector. These infectees were largely representative of the reported cases regarding age group, sex, and geographical location. The mean serial interval of 3.6 days (sd 3.4 days) from transmission pairs aligns with literature. Transmissions between age groups largely follow known contact patterns. Most transmissions in September 2021 occurred between persons who were not (fully) vaccinated, indicating the effectiveness of the vaccine, and relatively few between persons with different vaccination status, indicating assortative mixing in vaccination status. Conclusion Transmission pairs can be efficiently collected in routine surveillance, providing insight into disease transmission. The current post-pandemic period provides an excellent opportunity to adjust reporting systems for linking infectees to their most probable infector as preparation for future outbreaks.

Background: The global SARS-CoV-2 pandemic disrupted healthcare systems worldwide, raising concerns about its impact on clinical research. Early reports suggested reductions in participant enrollment, interruptions to ongoing trials, and challenges to protocol adherence, yet the magnitude and duration of these operational disruptions remain unclear. Methods: We conducted a registry-based analysis comparing clinical trials during the COVID-19 pandemic (December 2019 to November 2022) with a matched pre-pandemic cohort (December 2016 to November 2019). Studies were included if they reported any modifications to trial status, enrollment, or protocols during the study periods. Key variables included trial stoppage, enrollment changes, and adoption of remote or hybrid procedures. Results: The global SARS-CoV-2 pandemic resulted in widespread disruptions to trial operations with 13,323 clinical trials terminated, suspended or withdrawn over the course of the pandemic, a 38% increase compared to the 9,665 trials that stopped in the 3 years prior to the pandemic. Registries indicated a sharp decline in new participant enrollment across geographic regions and therapeutic areas, with partial recovery in later months. Review findings highlighted barriers including patient inaccessibility, staff redeployment, and supply chain interruptions. Conclusions: The pandemic caused system-wide operational shocks that compromised trial timelines and may have downstream methodological consequences. Recovery in enrollment does not imply restoration of pre-pandemic protocol fidelity or outcome ascertainment. Standardized reporting of disruptions, proactive contingency planning, and resilient trial designs are needed to maintain data integrity during large-scale disruptions and to support reliable evidence generation.

ABSTRACT OBJECTIVES To examine whether psychological safety and power distance are associated with medical researchers' well-being, and whether these associations operate through team inclusiveness and conflict. DESIGN Cross-sectional survey study. SETTING A biomedical research institute at a major UK university. PARTICIPANTS 133 medical researchers from 17 teams, including 20 principal investigators and 113 team members. MAIN OUTCOME MEASURES Job satisfaction, life satisfaction, intrinsic motivation, and psychological detachment. Mediators were dimensions of team inclusiveness and team conflict. RESULTS Psychological safety had no significant direct associations with job satisfaction, life satisfaction, intrinsic motivation, or psychological detachment, but showed several indirect associations through researchers' team experiences. It was indirectly associated with higher job satisfaction, life satisfaction, and intrinsic motivation primarily through greater integration of differences, inclusion in decision making, or more constructive forms of conflict (bs=.23-.38, ps=.032-<.001).For psychological detachment, psychological safety showed conflicting indirect associations: it had the potential to support detachment through greater integration of differences and lower avoidant conflict (bs=.21-.56, ps=.054-.002), but to undermine detachment through greater inclusion in decision-making (b=-.26, p=.082). Power distance showed a different pattern. Most notably, it was positively associated with psychological detachment (b=.54, p=.062). However, power distance was indirectly associated with lower job satisfaction, life satisfaction, and intrinsic motivation, primarily through reduced integration of differences and greater dominating conflict (bs=-.14 to -.19, ps=.068-.020). CONCLUSIONS Common assumptions about psychological safety and power distance should be revisited. Psychological safety did not show strong direct benefits for researcher well-being, whereas power distance was not uniformly harmful and was positively associated with psychological detachment. A more nuanced understanding of both cultural dimensions is needed in medical research teams.

Objectives: Diabetes affects over 500 million people globally and glycemia is inadequately managed. Metformin is the most frequently prescribed initial treatment for type 2 diabetes globally, yet glycemic response trajectories to metformin in routine real-world care and predictors of treatment response have not been well described. We aimed to identify glycemic response trajectories in adults prescribed metformin monotherapy as initial type 2 diabetes treatment and predictors of poor glycemic response to metformin. Design: Observational cohort study using latent class mixed models to identify hemoglobin A1c (HbA1c) trajectory classes, followed by random forests machine learning to predict trajectory class membership. Setting: US Veterans Affairs Healthcare System Participants: Adults treated with metformin alone for >30 days after diabetes diagnosis with a minimum of two HbA1c measurements from 90 days prior to two years after the first metformin prescription (N=140,413). Exposures: Demographic, laboratory, vital sign, and comorbidity data were included as predictors of metformin response trajectory Main Outcomes and Measures: We included all HbA1c measurements (487,604 total) for two years after metformin initiation to define metformin glycemic response trajectories. Results: We identified three HbA1c trajectories: stably low (89.7% of sample, mean HbA1c decrease from 7.2% to 6.6%), brisk response (7.1% of sample, mean HbA1c decrease from 11.4% to 7.0%), and non-response (3.1% of sample, mean HbA1c increase from 8.9% to 10.8%). Of those in the stably low and brisk response classes at 2 years, 91% maintained HbA1c at approximately 7% on metformin alone for 5 years after drug initiation. Prediction models could accurately predict brisk response (91% accuracy) but not metformin non-response (59% accuracy). Conclusions: Most individuals treated initially with metformin monotherapy have a beneficial and durable glycemic response. Predicting individuals who will not respond to metformin may be challenging but is evident within six months with recommended glycemic surveillance. The findings support current guidelines for HbA1c surveillance when initiating diabetes treatment.

Background: Atrial high-rate episodes (AHRE) detected by cardiac implantable electronic devices (CIEDs) are associated with increased thromboembolic risk, yet their clinical significance and optimal anticoagulation strategy remain uncertain, particularly in the absence of electrocardiogram (ECG)-confirmed atrial fibrillation. Methods: We conducted a nationwide cross-sectional survey of UK clinicians involved in CIED follow-up. The survey assessed anticoagulation decision-making in AHRE, including episode-duration thresholds, cumulative burden, CHA2DS2-VA use, additional ECG monitoring, and anticoagulant choice. Only responses from UK-based consultant clinicians were included and analysed descriptively. Results: A total of 51 responses were received; 38 met the inclusion criteria and were analysed. Most respondents (86.8%) reported having reviewed AHRE alerts within the preceding six months, indicating that AHRE are commonly encountered in clinical practice. A [&ge;]24-hour episode was the most common threshold for anticoagulation (44.7%), although many clinicians reported lower thresholds or individualised approaches. Nearly half (44.7%) did not consider cumulative AHRE burden in decision-making. CHA2DS2-VA thresholds also varied, most commonly [&ge;]2 or [&ge;]1. Additional ECG monitoring was infrequently performed. Direct oral anticoagulants were universally preferred, with apixaban the most commonly selected agent (73.7%). Conclusion: There is substantial variation in UK clinical practice regarding anticoagulation for AHRE, reflecting ongoing uncertainty and lack of clear guidance. These findings highlight the need for evidence-based thresholds to support consistent and informed clinical decision-making.

Rheumatic heart disease (RHD) is a leading preventable cause of cardiac death in children in low and middle-income countries. Nepals epidemiological data come mainly from auscultation surveys that miss subclinical disease, and no echocardiographic screening study had been conducted in Dhanusha district, a densely populated, low-income region in southern Nepal. We aimed to determine the prevalence of borderline and definite RHD among school children (6-16 years) in Dhanusha using the 2012 World Heart Federation (WHF) echocardiographic criteria, identify independent predictors, and quantify school-level clustering via the intraclass correlation coefficient (ICC). In a cross-sectional study (January 2023-December 2024), we screened 4,536 children from 8 public schools selected by four-stage cluster sampling. RHD was classified by WHF 2012 criteria; predictors were identified using random-effects logistic regression with school as random intercept. Ethical approval was from the Nepal Health Research Council (Protocol No. 155/2023). Overall prevalence of borderline or definite RHD was 18.7 per 1,000 (95% CI 15.1-23.0); definite RHD was 6.8 per 1,000 (95% CI 4.7-9.7) and borderline RHD 11.9 per 1,000 (95% CI 9.0-15.5). Prevalence was higher in girls (23.3 per 1,000) than boys (13.6 per 1,000; P=0.02), with the peak in girls aged 10-14 years (26.0 per 1,000). Subclinical disease accounted for 64.7% of cases; auscultation sensitivity was 35.3%. Mitral valve involvement predominated. Female sex was the sole independent predictor (OR 1.60, 95% CI 1.02-2.53; P=0.043). The school-level ICC was 0.19 (95% CI 0.07-0.44; P<0.001), giving a design effect of {approx}109. The echocardiographic RHD burden in Dhanusha (18.7 per 1,000) is the highest documented in Nepal. Two-thirds of cases are subclinical. Female sex and school attended explain a similar amount of variance in RHD risk, supporting school-targeted screening and informing sample size planning for future cluster-based surveillance.

Background: Statins are key to preventing atherosclerotic cardiovascular disease and lowering low-density lipoprotein cholesterol and cardiovascular events. However, skepticism regarding their safety and value persists and is increasingly influenced by social media. TikTok has emerged as a major source of health information, but its content varies in quality and accuracy. This study evaluated the quality, attitudes, misinformation, and engagement of statin-related content on TikTok. Methods: Public TikTok videos were collected using predefined search terms and coded by creator type, thematic content, and overall attitude. Video quality was assessed using the DISCERN instrument, the Patient Education Materials Assessment Tool for Audiovisual Materials, and the Global Quality Score. False or misleading claims were independently reviewed by two cardiology fellows. Associations between engagement and quality were also examined. Results: Of 1,349 screened videos, 258 met inclusion criteria. Most were educational (91.0%), with non-physician healthcare providers (34.5%) as the largest creator group. Risks or negative effects were discussed more often than benefits (63.2% vs 42.2%), and 39.5% contained at least one false or misleading claim, most often from complementary and alternative medicine providers and wellness promoters. Quality differed by creator type across all instruments, with physician-created content scoring highest. Video popularity showed minimal association with informational quality. Conclusion: Statin-related TikTok content frequently emphasizes harms, often contains misinformation, and varies substantially in quality by creator type. Greater involvement of healthcare professionals on social media may help improve digital health literacy and counter misleading information about statin therapy.

Aims CGM devices report glucose only within fixed limits (typically 40-400 mg/dL; 2.2-22.2 mmol/L), truncating extreme values to a boundary ("capping"). We characterised prevalence, duration, and consequences of capping in type 1 diabetes trial data. Materials and Methods We analysed 46,990,617 CGM readings from 948 participants across four publicly available clinical trial datasets (Dexcom G4 Platinum or G6 sensors). Capping prevalence, run duration, and associations with age, HbA1c and sex were characterised across all datasets. In the 77 participants of the Replace-BG trial CGM-plus-blood glucose monitor (BGM) arm, CGM-derived metrics were compared with contemporaneous BGM measurements across 1,162 non-overlapping 14-day windows. Results Between 93.5% and 100% of participants had at least one capped reading, and capped values comprised 0.47-0.98% of all readings. In the three datasets for which duration could be calculated, over 70% of upper-cap runs exceeded 15 minutes and over one third exceeded 60 minutes. Upper-limit capping was inversely associated with age (Spearman {rho} -0.20 to -0.47, p[&le;]0.002) in three of the datasets, and positively associated with baseline HbA1c ({rho} 0.39-0.62, p<0.001) in all four datasets. A within-participant analysis showed that capping burden did not predict CGM-BGM divergence in any summary metric (all p>0.2), and a systematic CGM-BGM offset in mean glucose and time in range (TIR) reflected the physiological lag between blood and interstitial fluid rather than capping artefact. Conclusions Sensor limit capping is near-universal in type 1 diabetes, produces sustained periods of right-censored glucose data disproportionately affecting younger patients, and does not substantially distort standard summary metrics at the population level. Clinicians and trialists should be aware that CGM data can confirm extreme glucose events but cannot quantify their severity.

Introduction: A prominent symptom of post-acute sequelae of SARS-CoV-2 infection (i.e., Long COVID) is exercise intolerance with or without post-exertional malaise (PEM). PEM is characterized by the worsening of both symptoms and function following even minor physical or mental exertion, with symptoms typically worsening 12 to 48 hours after activity and lasting for days or even weeks. Individualized, supervised cardiopulmonary rehabilitation is considered a safe and effective intervention for many cardiac and pulmonary conditions, and has been effective in gradually improving function in previously hospitalized and nonhospitalized patients with severe COVID-19. While traditional cardiopulmonary rehabilitation approaches appear helpful in some situations, the exercise intolerance symptoms experienced by many individuals with Long COVID may require a different approach, especially when attempts to increase physical activity result in PEM. No clear consensus exists on the optimal treatment of PEM, and no major studies have evaluated the efficacy in individuals with Long COVID of either carefully supervised, individualized cardiopulmonary rehabilitation programs for exercise intolerance without significant PEM or activity pacing interventions designed to treat or prevent PEM. Methods and Analysis: The Researching COVID to Enhance Recovery Clinical Trials (RECOVER-CT) initiative funded by the National Institutes of Health (NIH) included a prospective, multicenter, randomized controlled platform trial (RECOVER-ENERGIZE) designed to assess two interventions in patients with Long COVID and exercise intolerance: (1) cardiopulmonary rehabilitation for patients without significant PEM and (2) structured activity pacing to prevent or reduce PEM in participants who experience the symptom. The intervention duration will be 12 weeks. The primary endpoints for the trial include the Endurance Shuttle Walk Test as a measure of endurance capacity for the cardiopulmonary rehabilitation intervention and a modified version of the DePaul Symptom Questionnaire - Post-Exertional Malaise for the pacing intervention. Assessments will be completed at baseline, middle of intervention, end of intervention, and 12 weeks after completion of the intervention, and include physical performance measures and patient-reported surveys. Ethics and Dissemination: The RECOVER-ENERGIZE trial protocol has been approved by an institutional review board (Advarra), and written informed consent will be obtained from all participants prior to enrollment. The trial is registered on ClinicalTrials.gov (NCT06404047). Formally assessing PEM and developing a structured activity pacing intervention delivered by local pacing coaches are novel features of this trial. Results will be disseminated through peer-reviewed publications, presentations at scientific conferences, and communication with participants, patient advocacy organizations, and the broader Long COVID community. De-identified participant data will be made available through the NIH RECOVER data repository in accordance with NIH data-sharing policies. If successful, this protocol will provide accessible tools that clinicians can use to address exercise intolerance and PEM in patients with Long COVID.

OBJECTIVES To quantify socioeconomic inequalities in antibiotic prescribing for common infections in primary care, and assess whether these inequalities arise from differences in consultation frequency, prescribing behaviour, or variation in vaccination uptake, smoking, and body mass index. DESIGN Population based cohort study. SETTING Primary care data from Clinical Practice Research Datalink, England. PARTICIPANTS 17,195,399 children and adults estimated to have been registered with a general practice in 2019. MAIN OUTCOME MEASURES Antibiotic prescribing rates (prescriptions per person-year), consultation rates (consultations per person-year), and probability of receiving an antibiotic prescription following consultation. RESULTS Higher deprivation was associated with higher antibiotic prescribing rates for most respiratory tract indications. In children, prescribing rates were 44.8% (95% confidence interval [CI] 41.9% to 47.7%) higher for upper respiratory tract infections and 47.6% (95% CI 44.2% to 51.3%) higher for lower respiratory tract infections in the most versus least deprived twentile. In adults, prescribing rates for lower respiratory tract infections were 22.7% (95% CI 21.4% to 24.1%) higher in the most deprived twentile. Prescribing rates for other indications showed weak, U-shaped, or negative associations with deprivation. Prescribing inequalities were primarily driven by inequalities in consultation rates rather than probability of receiving antibiotics once consulted. Lower influenza vaccination uptake partly accounted for higher consultation rates for respiratory infections among more deprived children, while smoking prevalence contributed to inequalities among adults. CONCLUSIONS Socioeconomic inequalities in antibiotic prescribing vary by indication type and are largely explained by consultation frequency. Reducing inequalities may require interventions that decrease the need to consult, e.g. improving influenza vaccination coverage in children and reducing smoking among adults, rather than focussing solely on prescribing behaviour.

Background Post-acute sequelae are well described following COVID-19 but may also occur after other respiratory infections and Aedes-borne infections. Evidence remains fragmented due to heterogeneity in study design, populations, and exposure, outcome, and follow-up definitions. Methods We synthesized and compared post-acute sequelae across influenza, RSV-ARI, dengue fever, chikungunya, Zika, and yellow fever. We searched five databases from inception to 25-08-2025 for articles quantifying risk, incidence, or rates of post-acute sequelae following these diseases. Eligible non-randomized observational studies assessed post-acute neurological, psychiatric, gastrointestinal, cardiovascular, respiratory, renal, musculoskeletal, autoimmune, or endocrine outcomes after confirmed infection. Risk of bias was assessed using ROBINS-E. Random-effects meta-analyses with restricted maximum likelihood estimation were conducted when comparable effect estimates were available (PROSPERO #CRD420251124994). Findings 51 studies were included, predominantly from high-income regions. Most were retrospective cohorts using ICD-coded diagnoses; prospective studies used laboratory-confirmed infections. Data sources, comparator groups, exposure definitions, outcome ascertainment, and follow-up periods varied substantially. Meta-analyses were feasible for RSV, influenza, and dengue fever. All RSV-ARI studies were pediatric and assessed infections during infancy, which were associated with higher pooled odds of physician-diagnosed asthma (OR:2.93 [95%CI: 2.12-4.06]). Influenza studies used COVID-19-positive comparators; pooled estimates showed lower risk for neurological (HR:0.82 [0.76-0.89]) and composite outcomes (RR:0.88 [0.82-0.95]), with other organ systems non-significant. Dengue fever studies spanned all ages and showed increased risks of anxiety (HR:1.34 [1.01-1.78]), dementia (HR:1.61 [1.10-2.35]), autoimmune (RR:1.39 [1.17-1.67]), cardiovascular (HR:1.51 [1.27-1.80]), psychiatric (HR:1.17 [1.07-1.28]), and any sequelae (HR:1.19 [1.13-1.25]) versus those without prior infection. Interpretations Post-acute sequelae contribute to overall disease burden following RSV-ARI and dengue fever. The evidence remains limited by heterogeneity in study design, exposure and outcome definitions, comparator selection, and follow-up duration. Greater standardization in study design and reporting is needed to improve comparability and strengthen causal inference.