British Journal of General Practice

Objective The aim of this study was to develop and validate an automated, scalable framework to harmonise fragmented UK primary care prescription records into a research-ready dataset by mapping four diverse medical ontologies to a unified, historically comprehensive reference standard. Materials and Methods We used raw prescription records for consented participants in the UK Biobank, in which participants are uniquely characterized by multiple data modalities. Primary care data were preprocessed by selecting one drug code if multiple were recorded, cleaning codes to match reference presentations, expanding code granularity based on drug descriptions, and updating outdated codes to a single reference version. Harmonisation entailed mapping British National Formulary (BNF) and Read2 codes to dm+d, the universal NHS standard vocabulary for uniquely identifying and prescribing medicines. Harmonised dm+d records were then homogenised to a single concept granularity, the Virtual Medicinal Product (VMP). We validated our methods by creating medication profiles mapping contemporary drug prescribing patterns in 312 physical and mental health conditions. Results We preprocessed 57,659,844 records (100%) from 221,868 participants (100%). Of those, 48,950 records were dropped due to lack of drug code. 7,357,572 records (13%) used multiple ontologies. Most (76%) records were encoded in BNF and most had the code granularity expanded via the drug description (N=28,034,282; 49%). 41,244,315 records (72%) were harmonised to dm+d and 99.98% of these were converted to VMP as a homogeneous dataset. Across 312 diseases, we identified 23,352 disease-drug associations with 237 medications (represented as BNF subparagraphs) that survived statistical correction of which most resembled drug - indication pairs. Conclusion Our methodology converts highly fragmented and raw prescription records with inconsistent data quality into a streamlined, enriched dataset at a single reference, version, and granularity of information. Harmonised prescription records can be easily utilised by researchers to perform large-scale analyses in research.

BackgroundThe COVID-19 pandemic significantly accelerated the adoption of telemedicine, but it also exposed gaps in effective remote clinical assessment, particularly for medically vulnerable patients in rural areas. The ORCHARD intervention aimed to address this by providing patients with a Medical Self-Assessment Box to enable self-reporting of vital signs during remote consultations. MethodsA single-centre randomised mixed-methods feasibility trial recruited medically vulnerable patients from a rural general practice in Northeast Scotland. Participants in intervention group received a home medical equipment box for use during telemedicine consultations over six months. Patients and GPs were interviewed and transcripts were analysed using Framework Analysis. ResultsTwelve (15%) of 82 eligible invited patients enrolled. Six each were allocated to intervention and control group. 50%(n=3)patients in intervention group used equipment in 45%(5 of 11)teleconsultations and rated it helpful in all 5 uses (100%). The intervention group had 18% fewer primary care contacts than controls. All remote consultations were by telephone. Framework Analysis of patient interviews identified facilitators such as ease of use, improved triage access, reassurance, and barriers related to GP non-engagement and written instructions. GP interviews identified clinical value in patient-generated readings, alongside concerns regarding workload and patient over-monitoring. ConclusionsHalf of intervention participants used the medical-equipment box during remote consultations, all finding it useful, though frequency of use varied among particpants.A randomised controlled trial to evaluate the effectiveness of the Medical Self-Assessment Box for optimising remote consulting in medically vulnerable rural patients is feasible.Prior to a definitive trial refinements are recommended to patient labelling, GP engagement, and training materials.

Abstract Background Between 2021 and 2022, primary care obesity management was entering the early diffusion phase of newer anti obesity pharmacotherapy, as GLP1 based treatments began reshaping expectations. However, it was unclear whether primary care clinicians and practice environments were prepared to deliver comprehensive obesity care. (1,2) Methods In 2021 to 2022, we surveyed 276 clinicians from three cohorts: an opt-in national physician panel (Cohort A), clinicians from an integrated health system (Cohort B), and clinicians from a rural accountable care organization (Cohort C). The survey, informed by formative patient and physician focus groups conducted in 2021, assessed current and desired competence, attitudes, confidence, perceived forces for change, and barriers to obesity care. Analyses were descriptive (means and standard deviations). Results Across cohorts, desired competence exceeded current competence. The largest gaps involved recommending behavioral interventions, developing comprehensive care plans, and providing ongoing obesity management support. Attitudes toward obesity care were generally favorable, while confidence that current practices reflected best practice was only moderate. Professional and personal forces for change were moderate, patient driven motivators were moderate to high, whereas social (peer/organizational) reinforcement was weak. Reported barriers extended beyond knowledge deficits to include patient engagement, competing demands, cost, and practical constraints. Conclusions At the threshold of the GLP1 era, primary care clinicians were motivated to improve obesity care but lacked consistent support to deliver comprehensive management. The relative absence of peer and organizational reinforcement suggests that readiness for change reflected not only individual knowledge and attitudes, but also the degree of peer and organizational reinforcement that supports comprehensive obesity care in routine practice.

Aim To examine ethnic inequalities in recruitment outcomes and workforce representation across pay bands among nursing and midwifery staff, and to assess whether routinely collected administrative data can generate reproducible indicators for workforce equality monitoring. Design Retrospective observational study. Methods We analyzed routinely collected administrative data from one NHS Board in Scotland. This included annual staff-in-post data for 2021/22 to 2024/25 and pooled recruitment data on interviewed candidates and conditional job offers for 2021/22 to 2023/24. Ethnicity was grouped as White and non-White. Analyses focused on Bands 5, 6 and 7. Recruitment outcomes were assessed using relative risks for receipt of a conditional job offer among interviewed candidates, comparing White and non-White applicants. Workforce representation across pay bands was assessed using representation quotients. Analyses were descriptive and unadjusted. Results White applicants were more likely than non-White applicants to receive a conditional job offer following interview across all pay bands examined. Inequalities were also evident at Band 5, the usual entry point to registered practice. Workforce composition analyses showed a corresponding gradient in representation, with non-White staff overrepresented in Band 5 and underrepresented in Bands 6 and 7, with little change over the study period. Conclusion Routinely collected administrative data can generate reproducible indicators of ethnic inequality in recruitment and workforce representation. Embedded within existing workforce systems, such analyses could strengthen workforce equality monitoring, support benchmarking and enhance accountability across healthcare settings. Impact Utilising routine administrative data for workforce equality monitoring can support policy and practice aimed at improving accountability, retention and workforce sustainability across health systems. Reporting Method This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines. Patient or Public Involvement This study did not include patient or public involvement in its design, conduct, or reporting.

Objectives: Endometriosis affects approximately 10% of reproductive age women worldwide, yet care pathways remain fragmented and treatments have limitations. This study aimed to identify and categorize key stakeholders in endometriosis care in Ireland, assess their influence and interest in the digital health initiative, and identify drivers and barriers affecting uptake of innovative approaches to care. Methods: A virtual stakeholder mapping workshop was conducted with participants from healthcare, policy, education, technology, academia, and patient communities. Using a structured MS Teams Whiteboard, participants generated a stakeholder list, positioned stakeholders on an Influence-Interest Matrix, and provided qualitative insights on factors enabling or constraining engagement with digital health innovation. Results: Stakeholders were distributed across all four quadrants of the matrix. High-interest/high-influence stakeholders included the HSE, specialist centres, general practitioners, and the Endometriosis Association of Ireland. High-interest/low-influence groups comprised patients, families, and online communities, while policymakers, hospital managers, and the education sector were identified as high-influence but low-interest actors. Key drivers included strong patient advocacy, institutional support such as engagement from the HSE, and growing awareness of digital health tools. Major barriers encompassed prolonged diagnostic delays, resource constraints, gaps in clinical knowledge, technology anxiety, and challenges sustaining engagement. Conclusions: Stakeholder mapping provided an evidence-informed foundation for the VendoR project, revealing engagement gaps and leverage points critical for improving endometriosis care innovation. The findings highlight the need for intentional, well-resourced strategies that elevate patient voices, address systemic barriers, and ensure balanced representation, supporting the co-design, co-creation, and co-production of digital health interventions for sustainable, patient-centred care.

BackgroundHypertension is the leading modifiable risk factor for ischemic stroke, yet the adequacy of preventative hypertension care in routine clinical practice remains suboptimal. Whether gaps in hypertension management represent missed opportunities for stroke prevention remains unclear. ObjectiveTo evaluate the association between hypertension care delivery and the risk of incident ischemic stroke. MethodsWe conducted a retrospective, matched, nested case-control study among adults with hypertension using electronic health record data from a large regional health system (2010-2024). Patients with a first-ever ischemic stroke were matched 1:2 to controls on age, sex, race and ethnicity, and calendar time. Three care metrics were assessed during follow-up: (1) outpatient visits with blood pressure (BP) measurement per year; (2) number of antihypertensive medication ingredients; and (3) medication intensification score. Conditional logistic regression estimated adjusted odds ratios (aORs). ResultsThe study included 13,476 cases and 26,952 matched controls (N = 40,428). Mean (SD) age was 64.8 (12.2) years, 54.1% were female, and mean follow-up was 2,497 (1,308) days. Cases had fewer BP visits per year (median, 2.50 vs. 3.01; p < 0.001), similar number of medication ingredients (2.00 vs 2.00), and lower treatment intensification scores (-0.211 vs - 0.125). In adjusted models, >5 BP visits per year was associated with lower stroke odds (aOR, 0.55; 95% CI, 0.51-0.59) compared with [&le;]1 visit. Use of 2-3 medication ingredients (vs 0) was also associated with reduced stroke odds (aOR, 0.80; 95% CI, 0.75-0.86), whereas >3 ingredients was not significant. The highest quartile of treatment intensification showed the strongest association (aOR, 0.47; 95% CI, 0.44-0.51). Findings were consistent across subgroup and sensitivity analyses, including strata defined by baseline SBP and follow-up SBP. ConclusionsGreater engagement in hypertension care was associated with lower odds of ischemic stroke, suggesting that gaps in routine management may represent missed opportunities for prevention.

Background: Chronic conditions such as hypertension can significantly disrupt daily life and emotional wellbeing. The interaction between patients' perceptions, adherence to antihypertensive medication and quality of life (QoL) remains underexplored outside structured clinical settings. Objectives: To capture unprompted patient perspectives and assess whether hypertension affects QoL and to investigate if patient reported experiences are associated with self-reported antihypertensive medication adherence. Methods: Social media listening (SML) study analyzing 86,368 anonymized posts from individuals with hypertension in 12 countries, collected between January 2022 and May 2024. Posts from 11 countries (n=81,368) were analyzed using artificial intelligence-enabled natural language processing. Posts from China (n=5,000) were analyzed separately using a harmonized framework. Quantitative and qualitative methods assessed variations by country, age, and gender, and associations between emotional expression and antihypertensive medication adherence. Results: Across the 11-country core sample, 45% of posts mentioned at least one QoL impact, most commonly worry/anxiety (11%). Impacts varied across countries. Among 8,096 posts with age identified, individuals <40 years reported emotional balance impacts in 28% of posts versus 22% among those aged 40+. Work/Education impacts were mentioned in 17% of posts by those <40 years vs 12% in 40+. Among 7968 posts explicitly referencing adherence, expressed worry was associated with stricter adherence (62% association score), as were structured routines (79% score), home monitoring (77%), dietary changes (77%), and exercise (71%). In contrast, sadness/depression was associated with inconsistent adherence (71%), as were forgetfulness (79%), side effects (73%), and cost/insurance concerns (65%). Conclusions: These results emphasize the importance of the psychological and emotional impact of hypertension, including on adherence to medication regimens, reinforcing the value of a holistic approach to patient care.

Background India represents 18% of the global population yet remains underrepresented in health research. Moreover, existing national surveys miss critical variation across its 4,600 ethnolinguistic groups. We present a comprehensive phenotypic characterisation of 81 populations from the GenomeIndia project. Methods We analysed 67 sociodemographic, anthropometric, and blood biochemistry variables from 17,777 individuals sampled across 81 ethnolinguistic populations from India, examining population-level variation, disease reporting fractions, and age- and sex-specific life-course trends. Findings Ethnolinguistic identity predicted health outcomes independently of administrative state, improving phenotypic variance explained by an average of 7.4%. 95% of participants had at least one abnormal biochemical or anthropometric marker, driven by low HDL (52.2%) and elevated triglycerides (43.6%). Metabolic risk, however, was highly stratified: adjusted prevalence for low HDL ranged four-fold across ancestry groups from 17.2% to 67.7%. We also identified an "awareness gap"; only 17.6% of people with hypertension and 2.2% of people with dyslipidemia were aware of their condition. This awareness gap was higher in tribal populations, in which women did not show the higher HDL levels typically seen compared to men, pointing to distinct metabolic profiles and healthcare access barriers across India. Interpretation The Indian phenotypic landscape is highly structured along ethnolinguistic lines, where ancestry and environment both influence risk. The high systemic burden of abnormalities necessitates population-specific reference intervals. GenomeIndia provides a foundational map for precision public health, shifting the focus from state-level averages to population-specific risk profiles. Funding This work was funded by the Department of Biotechnology, Ministry of Science and Technology, Government of India.

BackgroundPaediatric liquid medicines (PLMs) routinely contain sucrose to improve palatability, yet their cariogenic potential is well established. Healthcare professionals awareness and prescribing practices regarding sugar-free PLMs have received limited study in India, particularly in Uttarakhand. MethodsA descriptive cross-sectional study was conducted among 500 healthcare professionals aged [&ge;]25 years, using a pilot-tested structured questionnaire (Cronbachs = 0.85), administered online and in person across Uttarakhand districts (January-March 2024). After excluding 69 incomplete responses, 431 participants were analysed (response rate: 86.2%), comprising general medicine practitioners (49%, n = 211), paediatricians (27%, n = 116), and dental practitioners (24%, n = 104). Descriptive statistics and chi-square tests were applied (p < 0.05). ResultsPrescription decisions were primarily driven by childs age and weight (58%), cost (40%), and pharmaceutical brand (37%). While 88% recognised PLM sweetness and 67% were aware of pH-dental harm links, only 20% associated PLMs with dental caries. Overall awareness of hidden sugars was 73%. Eighty-three percent knew of sugar-free alternatives (50% local availability), yet 80% found them less palatable and 85% costlier. Only 48% routinely provided oral health advice. A statistically significant association was found between specialty and sugar-free PLM awareness (p = 0.03), with dental practitioners recording the highest awareness (90%). ConclusionsHealthcare professionals demonstrated variable levels of knowledge, attitudes, and practices regarding PLMs, with critical gaps in caries recognition (20%) and oral health counselling (48%). Despite high sugar-free PLM awareness, uptake is constrained by perceived cost and palatability barriers. Targeted continuing medical education and policy measures, including sucrose-free labelling promotion, are needed to improve paediatric oral health outcomes in Uttarakhand. KEY MESSAGESO_LIOnly 20% of healthcare professionals in Uttarakhand associated pediatric liquid medicines (PLMs) with dental caries, representing a critical knowledge gap despite 88% recognising their sweetness. C_LIO_LIOverall awareness of hidden sugars in PLMs was 73%, yet only 48% routinely provided post-prescription oral health counsellingsubstantially below international benchmarks. C_LIO_LIEighty-three percent were aware of sugar-free PLM alternatives, but adoption was constrained by perceived inferior palatability (80%) and higher cost ([~]10% premium, cited by 85%). C_LIO_LIDental practitioners demonstrated significantly higher sugar-free PLM awareness than general practitioners and pediatricians (p = 0.03), supporting the case for interprofessional oral health education in medical training. C_LIO_LITargeted continuing medical education (CME) and policy measuresincluding sucrose-free labelling mandates and institutional formulary inclusionare needed to convert awareness into prescribing practice change. C_LI

Hormone replacement therapy (HRT) with oestrogen and progestogen is a common medical treatment for alleviating symptoms of menopause. Since 2015, its use has been increasing in the UK. Unscheduled bleeding can be a symptom of endometrial cancer, and guidelines state that women experiencing this should have an urgent referral for suspected endometrial cancer. However, unscheduled bleeding is also common in women taking HRT, particularly in the first few months after starting HRT or if there is a change in regimen. Current guidelines may result in women on HRT receiving referrals that are not necessary and undergoing unpleasant and invasive tests such as hysteroscopy. However, there is a lack of current information to guide recommendations. This protocol describes a cohort study in the ORCHID-e database of anonymised patient records from English primary care. We will use a cohort of women aged over 40 years starting on HRT with oestrogen and progestogen, age matched to women who have not started HRT. Exposure will be a prescription for oestrogen containing HRT with no previous prescription for oestrogen containing HRT in the previous year. Index date in each matched set will be the date of this prescription. Prescriptions for progestogen containing drugs will not be used to define the exposure, but this information will be extracted to describe the study population and for sensitivity analyses. Outcomes will be consultations for unscheduled bleeding, urgent referrals for suspected endometrial cancer, and diagnosis of endometrial cancer. Women will be followed up until they change exposure status or are otherwise censored. Women who start taking HRT in follow-up will re-enter the cohort in the exposed group. We will describe proportions of women with a code for consulting with unscheduled bleeding, proportions of those women referred for further investigation on the pathway for suspected endometrial cancer, and proportions diagnosed with endometrial cancer within one year of referral. We will investigate the diagnostic accuracy of unscheduled bleeding for endometrial cancer separately for women on HRT and those not on HRT. Analyses will be done by 6-month categories of time since index, age, calendar year, sociodemographic variables, risk factors for endometrial cancer, type of HRT.

Background and hypothesis Autosomal dominant polycystic kidney disease (ADPKD) affects over 12 million people worldwide including an estimated 30,000-70,000 in the United Kingdom (UK). Tolvaptan is the only disease-modifying therapy approved for rapidly progressing disease. Despite national guidance, prescribing rates were hypothesised to vary by kidney centre. Treatment may not always align with guidelines: some patients eligible for tolvaptan may not be initiated, while other patients initiated on tolvaptan may not meet eligibility criteria. This may have important consequences for healthcare costs and health-related quality of life. Methods The National Registry of Rare Kidney Diseases (RaDaR) collects longitudinal data from UK NHS kidney centres. This retrospective cohort study used routinely collected data (2016-2023) to examine tolvaptan prescribing across kidney centres. Kidney centre-level initiation patterns were described, assessed using mixed-effects logistic regression and visualised with funnel plots. Cost-effectiveness analyses combined observed prescribing practices under likely negotiated commercial discounts to estimate costs and quality-adjusted life year (QALY) consequences of prescribing at the national level. Results Our study included 3,609 people with ADPKD from 72 kidney centres. Patients eligible for tolvaptan who were not initiated accounted for 34.8% (292/839). Across centres, five (6.9%) initiated tolvaptan significantly more than expected among eligible participants, while one centre (1.4%) initiated significantly less. Nationally, this could result in up to {pound}53.7 million in lost savings (assuming a 60% medication price reduction) and result in up to 1,245 lost QALYs. Patients initiated on tolvaptan who were not eligible accounted for 26.1% (103/395). Only one centre had significantly fewer eligible patients than expected among initiated patients. Nationally, this could cost up to {pound}15.9 million (assuming a 60% medication price reduction). Conclusions There is evidence of variation in tolvaptan prescribing in the UK. A substantial proportion of patients eligible for tolvaptan were not initiated at the cohort-level, with evidence of variation between centres suggesting differences in treatment decision-making. A substantial proportion of patients initiated on tolvaptan were not eligible at the cohort-level, but there was limited evidence of variation between centres. Together, these findings raise questions regarding the potential consistency of clinical decision-making, equitable access to a sole disease-modifying therapy in a rare disease, alignment with national guidance, and effective use of healthcare resources.

Background Regulatory inconsistency across African countries contributes to duplicative scientific assessments, prolonged approval timelines, and delayed access to essential medical products. To inform the operationalisation of the African Medicines Agency (AMA), the African Medicines Regulatory Harmonisation (AMRH) programme implemented Africa's first continental pilot study for the scientific evaluation and listing of human medicinal products. This study evaluates the pilot's procedural performance and examines how continental scientific opinions were translated into national regulatory decisions through reliance mechanisms. Methods and Findings A mixed-methods programme evaluation was conducted using regulatory datasets generated during the pilot study. Quantitative data included assessment timelines, GMP inspection outcomes and national post-listing regulatory actions. Retrospective qualitative thematic analysis was applied to governance documents and National Regulatory Authority (NRA) feedback to identify legal, institutional and procedural determinants influencing uptake. Of 64 expressions of interest, 24 products progressed to full evaluation and 12 received positive continental scientific opinions. Ten met the predefined performance target of [&le;]210 working days. Twenty-four GMP inspections identified no critical deficiencies and aligned with global regulatory benchmarks. National uptake demonstrated active reliance: full reliance (continental opinion as primary basis for national approval) for 7 products (58%); sequential reliance (continental assessment supplemented with targeted national queries) for 3 products (25%); and supplemented national review (separate national assessment undertaken) for 2 products (17%). Products with broader market strategies achieved registration in up to 23 African countries within a median of 77 working days post-listing. Variability in uptake reflected national legal authority, administrative requirements, and applicant submission strategies Conclusions The pilot study demonstrates the feasibility of a continent-wide regulatory assessment mechanism capable of producing trusted scientific outputs and enabling reliance-based national decision-making in Africa. While reliance was widely applied, heterogeneity in national procedures and administrative sequencing affected time to national registration. Findings provide empirical evidence to inform the AMA scale-up, highlighting the need for harmonised reliance pathways, streamlined administrative processes, and coordinated digital regulatory infrastructure.

Background: Lung cancer screening can reduce lung cancer mortality through early detection, but uptake of the NHS Targeted Lung Health Check (TLHC) programme remains low. Behaviourally informed invitation messages have been proposed as a low-cost approach to increase attendance, but evidence of their effectiveness in lung cancer screening is mixed. Few intervention studies used evidence-based behaviour change frameworks, and rarely tailored invitation strategies to empirically identified barriers and enablers. Methods: In an online experiment, 3,274 adults aged 55-74 years and with a history of smoking were randomised to see one of four behaviourally informed invitation messages or a control message. Participants then rated their intention to attend a TLHC appointment, and selected barriers and enablers to attending from a pre-defined list, which were classified according to the Theoretical Domains Framework. Invitation messages were mapped to Behaviour Change Techniques using the Theory and Techniques Tool. Message conditions were compared on intention to attend TLHC using bootstrapped ANOVA followed by pairwise comparisons. Exploratory counterfactual mediation analyses examined the role of fear in intention to attend. Results: Behaviourally informed invitation messages did not meaningfully increase intention to attend TLHC compared with the control message. While a GP-endorsed message showed a small potential benefit relative to the other conditions, this finding was not robust after adjustment for multiple comparisons. Participants most frequently reported barriers related to Emotion (particularly fear), Social Influence, and Knowledge, while Beliefs about Consequences emerged as the primary enabler of attendance. Only around half of reported barriers and enablers were addressed by the invitation messages. Exploratory analyses found that fear was associated with lower intention to attend a TLHC appointment, yet none of the behaviourally informed messages appeared to reduce fear compared to the control message. Conclusions: Improving lung cancer screening uptake will likely require invitation messages that directly address emotional concerns, particularly fear, alongside credible recommendations. These findings highlight the importance of systematically aligning invitation message content with empirically identified behavioural influences when designing scalable interventions to improve lung cancer screening uptake.

Background: Previous recommendations on screening for prostate cancer relied on ongoing trials of screening with prostate-specific antigen (PSA), which may have lacked sufficient follow-up duration to fully examine effects on mortality and overdiagnosis. Findings which consider absolute effects by age and screening intensity, along with newer guidance for assessing evidence certainty, may lead to different interpretations. Adding magnetic resonance imaging (MRI) to PSA-based screening has been raised as a way to reduce false positives (FPs) and overdiagnosis. Methods: We systematically searched MEDLINE, Embase, and Central from 2014 to January 28, 2026, for randomized controlled trials (RCTs) and prospective observational studies of: (i) screening versus no screening and (ii) sequential screening with MRI for those with a positive PSA test versus PSA alone among men not known to be at high risk for prostate cancer. Studies on screening with PSA or digital rectal examination (DRE) published pre-2014 were identified from existing systematic reviews and reference lists. Studies on FPs and complications from biopsies after PSA screening did not require a control group. Paired reviewers screened titles/abstracts (assisted with artificial intelligence) and full texts, assessed risk of bias, and extracted data, by age when available. We pooled data when suitable using random-effects models, investigated heterogeneity, and assessed the certainty of evidence using GRADE with conclusions of effects based on decision thresholds based on absolute effect sizes. Results: Across both questions, we included 15 RCTs (N=856,000; 8 sites of ERSPC considered separate trials) and 8 observational studies (N=56,122). At 20 years, among 1000 men who underwent repeated PSA-based screening every 2-4 years starting from age 55-69 (mean 62), there is likely a reduction in prostate-cancer mortality ([&ge;]2 fewer) and metastatic cancer incidence ([&ge;]6 fewer), at the expense of prostate-cancer overdiagnosis ([&ge;]24 cases) and FPs ([&ge;]150 cases) (all moderate certainty). If screening starts at age 50-54 or age 55, the benefits are probably smaller (e.g., 1 vs. 2 fewer prostate-cancer related deaths) with similar harms. Adding DRE or screening with PSA annually does not add benefit. One round of PSA screening or starting screening later at age 70-74 may not offer any important benefit or harm (low to moderate certainty), and any benefit from screening primarily with DRE was not shown. Compared with PSA alone, sequential screening with PSA followed by MRI reduces FPs ([&ge;]33 fewer) and overdiagnosis (via [&ge;]10 fewer diagnoses of clinically insignificant [e.g., Gleason 6] cancers without impacting detection of clinically significant cancers) (moderate to high certainty), though findings were limited to one round of screening without long-term follow-up or measurement of mortality. Interpretation: This review provides clinicians and other interest holders with anticipated absolute effects by age, and assessments of certainty across critical and important outcomes and with approximately two decades of follow-up. Findings apply to a general population and may differ for specific groups. Results for most critical outcomes, both benefits and harms, exceeded thresholds for clinically important effect sizes, thereby demonstrating the complexity of guideline developers' and patients' decision-making regarding screening trade-offs. Findings about adding MRI for those with a positive PSA test were limited and would require additional consideration of costs, infrastructure, expertise, and equity. Protocol registration: PROSPERO - CRD420250651056.

Importance: Glucagon like peptide 1 receptor agonists (GLP 1 RAs) and dual glucose dependent insulinotropic polypeptide/glucagon like peptide 1 receptor agonists have demonstrated what may be considered transformative efficacy in recent randomized clinical trials for the treatment of obesity, yielding substantial weight loss in a majority of participants. However, the extent to which these trial results translate into routine clinical practice particularly within the rapidly expanding direct to consumer (DTC) telehealth sector serving self pay populations remains insufficiently characterized. As access to and affordability of these therapies broaden beyond traditional insurance based care models, evaluating real world effectiveness, safety, and patient engagement among individuals shouldering the full financial cost of treatment is essential for informing future models of obesity care delivery. Objective:To assess long term medication specific weight loss outcomes, including gender specific responses and discrepancies, and explore usage trends in a real world, self pay telehealth cohort receiving GLP 1 RA therapy, using an Observational study design (Retrospective data analysis). Setting and Participants:Retrospective data of patients enrolled in electronic health records (EHR) from Carevalidate, a national US telehealth platform provider for Online TeleHealth companies. The data collected ranged for a total of 703 days from January 12, 2024, to December 15, 2025. The analysis included 572 adults with overweight or obesity diagnosis who initiated treatment with semaglutide or tirzepatide and completed a minimum of 9 months of active follow up. Patients with insufficient follow up or those utilizing insurance coverage were excluded to isolate the self pay phenotype. Exposures: Prescription of semaglutide or tirzepatide (injectable or oral formulations) via synchronous or asynchronous telehealth consultations, titrated according to standard clinical protocols adapted for patient tolerance and financial sustainability. Main Outcomes and Measures: The primary outcome was percentage total body weight loss (%TBWL) from baseline to the last recorded encounter. Secondary outcomes included categorical responder rates (5%, 10%, 15%, >20% weight loss), weight loss velocity analysis, and telehealth utilization metrics (frequency of encounters and visit intervals) including gender differences in approaching the telehealth program. Results: The final analytical cohort included 572 patients (79.2% female; 20.8% male). Overall, 95.8% (548/572) achieved weight loss, while 3.7% experienced weight gain. At 12 months, the mean %TBWL was 13.8% for the semaglutide cohort (n=450) and 12.5% for the tirzepatide cohort (n=122), with no statistically significant difference between the two medications (P >.05), contrary to standard clinical trial data suggesting tirzepatide superiority. A significant gender difference was observed: females were significantly more in number comprising 80% of the cohort and were likely to be "major responders" (>20% weight loss) compared to males (29.8% vs 5.9%; P <.001). Conversely, males demonstrated significantly higher utilisation rates, attending more frequent encounters (mean 13.5 vs 12.7; P =.028) with shorter intervals between visits (35.6 vs 44.1 days; P =.009) compared to females. Weight loss velocity for both medications peaked during months 1 to 3 (~1.07 lbs/week) and declined substantially by months 12 to 15, indicating a plateau effect independent of the specific agent used. Conclusions and Relevance: Telehealth-managed GLP 1 treatment in a self pay population demonstrates high efficacy comparable to clinical trials for semaglutide. However, tirzepatide outcomes fell short of trial benchmarks, likely due to economic barriers preventing optimal dose titration and lower sample size. The study identifies a discrepancy where females approach the telehealth based self pay system more but males engage more frequently with the digital platform which could be due to inferior physiological outcomes ( less weight loss and more non responders) compared to females.This suggests that while telehealth is a viable model for long term obesity care, the "one size fits all" approach may be insufficient for under responders, who may require distinct titration strategies or tailored behavioral interventions to overcome baseline genetic and biological resistance.

Background: Lifestyle interventions incorporating medically-tailored meal delivery may support rapid behavior change among pregnant individuals with gestational diabetes (GDM). Purpose: To examine the feasibility and acceptability of a multicomponent lifestyle intervention for pregnant individuals with GDM. Primary outcomes included recruitment, retention, intervention receipt, and acceptability. Methods: We conducted a pilot randomized feasibility trial among pregnant individuals with GDM recruited from maternal fetal medicine clinics in the Hartford, Connecticut area. Participants were randomized to usual GDM care or the Meals4Moms intervention plus usual care. The intervention included medically-tailored meal delivery, personalized physical activity support, and multimodal education with digital tools. Participants completed a survey and three 24-hour dietary recalls at baseline and post-intervention. Meals4Moms participants also completed a semi-structured interview at follow-up. Intervention receipt was tracked by study staff. Results: Of 30 individuals approached, we screened 80% (n=24), of whom 75% (n=18/24) were eligible; we randomized 8 participants. Seventy-five percent (n=6/8) completed at least one component of the follow-up assessment (100%, n=4/4 Meals4Moms, 50%, n=2/4 Usual Care). One participant spent [&ge;]80% of her total food budget (n=1/4, 25%), and no participants completed [&ge;]80% of prescribed exercise sessions (range: 0-50%). All (n=4) Meals4Moms participants reported they would be very likely to participate in the program if they had GDM again, and 100% (n=4) would be very likely to recommend the program to a friend with GDM. Conclusions: While the Meals4Moms intervention was highly acceptable to participants, procedural refinements are needed prior to conducting a full-scale efficacy trial.

Introduction: Although temporal variation is the hallmark of asthma, recommended diagnostic approaches largely rely on single clinic-based measurements. Ambulatory monitoring captures diurnal and day-to-day variability and may therefore enhance diagnostic accuracy. We evaluated the clinical feasibility and potential utility of home spirometry and fractional exhaled nitric oxide (FeNO) monitoring in asthma diagnosis. Methods: Symptomatic, untreated adults with GP-suspected asthma underwent diagnostic tests including bronchodilator reversibility, in-clinic FeNO, blood eosinophil counts and bronchial challenge. Participants measured spirometry and FeNO four times daily over one week; during the second week spirometry were measured twice daily. The reference standard was provided (asthma/not-asthma) by an expert panel of at least two asthma specialists based on clinical history and the results of all in-clinic testing; home spirometry (except for peak expiratory flow) and FeNO measurements were blinded to the panel. Results: Of 67 eligible participants, 51(76%) were recruited, and 38 had asthma confirmed or excluded by the panel. 1058 home spirometry measurements were obtained from 37(73%) participants; 848 home FeNO readings were obtained from 39(76%) participants. Among those completing at least one home measurement, median (IQR) adherence was 66.7(58.6-97.6)% for spirometry and 78.5(51.8-103.6)% for FeNO. Collection of health impact data for economic evaluation was feasible. In participants with a confirmed diagnostic outcome who completed home measurements (FeNO: n=32; spirometry: n=28), the putative home-testing metrics demonstrated high sensitivities at [&ge;]90% specificity, and outperformed peak expiratory flow diurnal variability. Incorporating home testing into the BTS/NICE/SIGN 2024 diagnostic pathway had the potential to reduce reliance on bronchial challenge testing by 57%. Conclusions: Home spirometry and FeNO testing and the prospective collection of health-economic data in the diagnostic setting were feasible. Home-based testing strategy showed early potential to improve asthma diagnosis and pathway efficiency. These findings support further evaluation through an adequately powered diagnostic accuracy study and health-economic assessment.

Background: The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline lowered diagnostic threshold for hypertension, encouraging earlier treatment initiation in the U.S. compared to UK, where the National Institute for Health and Care Excellence (NICE) guideline recommends higher thresholds. No comparative study evaluating how different hypertension guidelines and physical activity are jointly associated with mortality outcomes in two countries. Aims: This study compared hypertension prevalence, treatment uptake, blood pressure (BP) levels, and mortality between the UK Biobank (UKBB) and the U.S. National Health and Nutrition Examination Survey (NHANES). We evaluated whether moderate-to-vigorous physical activity (MVPA) modifies mortality risk among different hypertension subgroups (normotensive, medicated hypertension, and unmedicated hypertension). Methods: We harmonized demographic, biomarker, lifestyle, and accelerometer data from UKBB (n=63,452) and NHANES (n=7,397). Comprehensive weighting methods were applied in both cohorts. Accelerometry data was classified using a validated two-stage machine learning Random Forest algorithm. Associations between MVPA and all-cause mortality were examined with restricted cubic spline regression and visualized using Kaplan-Meier survival curves. Results: NHANES showed a higher proportion of treated hypertension (29.9%) and lower average blood pressure (SBP/DBP: 122.2/70.7 mmHg) compared to UKBB (11.7% treated; SBP/DBP: 136.0/81.3 mmHg). Despite lower BP levels, cardiovascular mortality was higher in UKBB (10.3 per 10,000 person-years) compared to NHANES (4.0 per 10,000 person-years). In both cohorts, greater MVPA was linked to lower mortality risk, with the strongest association observed among medicated hypertensives. Notably, NHANES participants with treated hypertension and low MVPA (<10.7 minutes/day) experienced a steeper survival decline, falling to 74% by year 8, compared to 91% in normotensives and 79% in untreated hypertensives. Conclusion: Despite higher treatment prevalence and lower average BP levels in NHANES, mortality remained higher compared with UKBB, suggesting that differences in mortality patterns may relate to broader cardiometabolic profiles and PA patterns beyond pharmacological management alone. Across both cohorts, higher levels of MVPA were associated with lower all-cause mortality, with the strongest associations were observed among individuals with medicated hypertension.

Study questionWhat are the characteristics and treatment outcomes of women who undertook planned egg freezing (PEF) in Australia and New Zealand between 2009 and 2023? Summary answerThere has been an average yearly increase in the uptake of PEF of 35%, with most women undergoing a single PEF procedure in their mid-thirties. Given ten years follow-up a little over one in four women return, with nearly half of those using donor sperm and one-third achieving a live birth. What is known alreadyPEF, where women freeze their eggs as a strategy to preserve fertility, has increased dramatically in high income countries in the last decade. Despite the rapid uptake of PEF, there remains limited information to guide women, clinicians and policy makers regarding the characteristics of women undertaking this procedure and treatment outcomes. Study design, size, durationA retrospective population-based cohort study of all women who undertook PEF in Australia and New Zealand between 2009 and 2023, including their subsequent return to thaw their eggs and treatment outcomes. Where women returned to utilise their eggs, all subsequent embryo transfer procedures were linked enabling calculation of live birth rates per woman. Participants/materials, setting, methods20,209 women who undertook PEF in Australia and New Zealand between 2009 and 2023 including 1,657 women who returned to thaw their eggs. Main results and the role of chanceThere has been a huge increase in uptake of PEF, from 55 women in 2009 to 4,919 in 2023. Women who freeze their eggs are typically aged 34-38 years (interquartile range) and nulliparous (98.6%). For women with at least 10 years follow-up (i.e. undertook PEF in 2009-13; N=514), 27.9% returned and thawed their frozen eggs (average time to return: 4.9 years). This reduced to 22.1% in those with at least 5 years follow-up (i.e. undertook PEF in 2009-2018; N=4,288). Of those who used their frozen eggs, 47% used donor sperm. After at least two years follow up, 33.9% had a live birth, rising over time to 37.8% for eggs thawed between 2019-2021. Limitations, reasons for cautionIn the timeframe 2009-2019 we did not have information on whether egg freezing occurred because of a cancer diagnosis, a cohort we wished to exclude from the study. As a result, for this timeframe we weighted observations by the probability that egg freezing occurred due to cancer, with the prediction model developed on the years 2020-2023. Wider implications of the findingsThis study provides recent and comprehensive data on PEF to guide prospective patients and clinicians and inform policy. The exponential growth in PEF in Australia and New Zealand mirrors trends in other high-income countries, suggesting a doubling time of 2-3 years. Study findings highlight the need for setting realistic expectations about the likelihood of returning to use frozen eggs and live birth rates. Study funding/competing interest(s)2020-2025 MRFF Emerging Priorities and Consumer Driven Research initiative: EPCD000014

Purpose: To understand how the Philips PAP device recall affected patient experiences, clinical practice, and health system responses. Methods: From November 2022 to August 2023, we interviewed individuals with OSA, physicians, respiratory therapists and health system leaders. We also received emailed responses from Health Canada. Interviews explored participants' experiences with the recall announcement and communication, their own responses and perceptions of actions taken by others, the overall impact of the recall and suggestions for improving future recall processes. Interviews were analyzed using an inductive thematic approach. Results: We interviewed 47 participants (16 individuals with OSA, 10 physicians, 17 public or private respiratory therapists, five health system leaders). Themes were organized into four domains: recall communication, execution, participant experiences, and the policy and regulatory context. Participants were confused due to inadequate information from Philips throughout the process. The burden of notifying patients and tracing devices mostly fell to healthcare providers and vendors, while replacement efforts were disorganized and frustrating. Individuals with OSA experienced emotional distress over therapy decisions and difficulties navigating the recall. Healthcare providers described moral distress from being unable to support patients adequately, and vendors faced additional logistical and financial strain. While regulatory authorities reported that Philips followed standard procedures, participants expressed a loss of trust in both the manufacturer and oversight systems. Conclusions: Interviews revealed that poor communication and execution of the Philips recall caused confusion, frustration and significant emotional and financial burden. Collaborative, context-specific strategies are required to improve future recalls.