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British Journal of General Practice

● Royal College of General Practitioners

Preprints posted in the last 30 days, ranked by how well they match British Journal of General Practice's content profile, based on 23 papers previously published here. The average preprint has a 0.03% match score for this journal, so anything above that is already an above-average fit.

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Social prescribing for patients with severe mental illnesses: an English primary care longitudinal observational study

Burton, A.; Launders, N.; Taylor, A. E.; Richards-Belle, A.; Osborn, D.; Tierney, S.; Fancourt, D.; Bu, F.

2026-10-02 primary care research 10.64898/2026.10.01.26364429 medRxiv
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Background People diagnosed with severe mental illnesses (SMI) including bipolar disorder, schizophrenia and psychosis are disproportionately exposed to adverse social determinants of health, contributing to premature morbidity and mortality. Social prescribing aims to address social risk factors for poor health by linking patients in primary care to community activities. However, whether people with SMI access social prescribing through primary care remains unexplored. Aims To describe prevalence of, and sociodemographic characteristics associated with, social prescribing consultations in patients with SMI in primary care. Methods Using the UK Clinical Practice Research Datalink, we identified patients aged 18+ with a diagnosis of SMI between 2004-2019. We calculated the percentage of patients with SMI who received a social prescribing consultation between 2019-2023 and used logistic regression to examine associations between sociodemographic, health-related factors and social prescribing consultations and refusals. We used fixed effects analysis to determine whether a new diagnosis of SMI made between 2019-2023 was associated with an increased odds of receiving a social prescribing consultation. Results Among 112,334 patients with SMI, 0.8% received a social prescribing consultation in 2019 increasing to 9.5% in 2023. Between 2020-2023, older age (OR=1.18-2.34), being female (OR=1.16-1.31) and living in more deprived areas (OR=1.14-1.49) were associated with higher odds of receiving a social prescribing consultation amongst patients with SMI. Across all years, patients with SMI and depression (OR=1.32-1.92), diabetes (OR=1.19-1.35) or obesity (OR=1.17-1.54) also had increased odds. In 140,514 patients with time-varying SMI status, a new diagnosis of SMI was associated with higher odds of receiving a social prescribing consultation (OR=1.39, 95% CI 1.26-1.53). Conclusion Since 2019, social prescribing consultations among patients with SMI in primary care have increased and are reaching those in areas of higher deprivation and with greater health needs. Strategies to remove barriers to consultations among younger adults and males are still needed

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When Prescribing Diverges From Published Lactation Compatibility Guidance: A National Claims Analysis

Krutsch, K.; Appiah, D.

2026-10-21 epidemiology 10.64898/2026.10.19.26365940 medRxiv
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Purpose Prescribing to lactating women is constrained by limited evidence. Published compatibility classifications provide clinical guidance and a discrete research comparator. How often prescribing diverges from that guidance, and what characteristics are associated with divergence, is unknown at national scale. Methods Retrospective analysis of prescriptions filled during lactation, identified in the 2012-2014 MarketScan Commercial Claims Database. Prescriptions were classified as concordant (Hale's lactation risk category L1-L3) or discordant (L4-L5). Multivariable logistic regression identified factors associated with concordance. Results Of 96,484 new prescriptions, 95,710 (99.2%) were concordant and 774 (0.8%) were discordant. Discordant prescriptions were filled later after delivery (median 59 vs 33 days) and had a day supply three times longer (30 vs 10 days). In multivariable analysis (N=28,732), concordant prescriptions were associated with maternal age under 35 (adjusted odds ratio (aOR)=1.34, 95% confidence interval (CI): 1.02-1.75) and chronic-condition medications (aOR=10.94, 95% CI: 6.47-18.50), and were less likely within 14 days of delivery (aOR=0.53, 95% CI: 0.38-0.73) and with each additional day of supply (aOR=0.96, 95% CI: 0.96-0.96). Compared with family practice, concordance did not differ for obstetric, internal medicine, or emergency medicine prescriptions, but prescriptions from other provider types had lower odds of concordance (aOR=0.57, 95% CI: 0.41-0.79). Conclusions Prescribing during lactation was overwhelmingly concordant with published compatibility guidance; the rare divergence was patterned by prescription and prescriber characteristics. Because the categories are an expert classification rather than consensus guidance, divergence should not be read as inappropriate prescribing.

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Evaluating the impact of Advice and Guidance on diagnostic pathways and healthcare use in England: retrospective cohort study, 2015-2022

Mason, K. J.; Welsh, V. K.; Jordan, K. P.; Bailey, J.; Bajpai, R.; Clarson, L. E.; Faux-Nightingale, A.; Hadley-Barrows, T.; Haines, J. K.; Harrison, R.; Helliwell, T.; Hider, S. L.; Jinks, C.; Knight, N.; Mallen, C. D.; Burton, C.

2026-10-11 primary care research 10.64898/2026.10.08.26365047 medRxiv
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Objective: To determine outcomes by referral route (any Advice and Guidance [A&G] versus elective referrals only) for patients with inflammatory bowel disease (IBD), Parkinson's disease, and systemic lupus erythematosus (SLE). Design: Population-based retrospective cohort study. Setting: Linked Clinical Practice Research Datalink (CPRD) Aurum primary care records, 2015-2022. Participants: Patients with incident diagnosis of IBD, Parkinson's disease, or SLE. Main Outcome Measures: Time from the earliest recorded A&G or elective referral to diagnosis, first recorded definitive treatment and first attended outpatient appointment. Secondary outcomes included counts of primary care consultations, prescriptions, referrals, and outpatient appointments. Propensity score weighted flexible parametric survival analyses accounted for differences between exposure groups. Results: Among 71,145 eligible patients, A&G was recorded for 1,137 (3.0%) with IBD, 971 (3.4%) with Parkinson's, and 243 (4.9%) patients with SLE. Compared with elective referral only, A&G was associated with slower time to diagnosis for IBD (adjusted median difference 15.9 weeks; hazard ratio 0.58, 95% confidence interval 0.52 to 0.66), Parkinson's disease (11.4 weeks; 0.57, 0.51 to 0.64), and SLE (6.3 weeks; 0.82, 0.73 to 0.91). However, A&G was not associated with a longer time to treatment or first attended outpatient appointment. An increase in primary care consultations following A&G was observed in patients later diagnosed with IBD and SLE. Conclusion: A&G was associated with a longer diagnostic interval than elective referral only. These findings do not establish that A&G caused diagnostic delay. A&G might be used at an earlier stage of more complex diagnostic pathways.

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Exploring associations between trust in doctors and the likelihood of accessing healthcare for anxiety, depression and menstrual problems

Hoque, D.; Wootton, R. E.; Haworth, C. M. A.; Easey, K. E.

2026-10-01 primary care research 10.64898/2026.09.30.26364328 medRxiv
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Background Anxiety, depression and menstrual problems are conditions that significantly impact an individual's health and wellbeing yet, barriers to healthcare can prevent access to appropriate medical care. Trust in doctors is a notable factor as previous studies have shown that it affects engagement with healthcare services and has declined in recent years. Methods Using the Avon Longitudinal Study of Parents and Children, we investigated associations between trust in doctors and healthcare access at two timepoints, for anxiety, depression (mothers and partners) and menstrual problems (mothers only). Results Mothers reporting greater trust in doctors were more likely to access care for anxiety (n=1849, adjusted odds ratio (AOR) 1.11, 95% confidence interval (95% CI) 1.08-1.14), depression (n=2411, AOR 1.10, 95% CI 1.07-1.12), and menstrual problems (n=1723, AOR 1.04 95% CI 1.01-1.06). If mothers and partners endorsed 'the doctor is always helpful', they were more likely to access care for depression (mothers: n=2005, AOR 1.30, 95% CI 1.16-1.46; partners: n=580, AOR 1.46, 95% CI 1.05-2.03) and for anxiety (mothers: n=1892, AOR 1.35, 95% CI 1.19 to 1.54; partners: n=734, AOR 1.40, 95% CI 1.02-1.91). Implications This study supports association between trust in doctors and healthcare access for anxiety, depression and menstrual problems, particularly amongst mothers. This contributes to previous literature that suggests that trust remains an important factor in understanding treatment gaps, and that researchers and clinicians must work to improve public trust in healthcare systems.

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Accuracy and completeness of death recording in primary care electronic health records compared with national death registrations in England using OpenSAFELY-TPP

Pesce, M.; Hulme, W. J.; Kyomuhangi, I.; Prestige, E.; Evans, D.; Wong, S. Y.; Goldacre, B.; Bacon, S. C.; Mehrkar, A.; OpenSAFELY Collaborative, ; MacKenna, B.; Schaffer, A. L.

2026-10-15 epidemiology 10.64898/2026.10.14.26365028 medRxiv
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Introduction: Primary care electronic health records (EHRs) are an important resource for health research, but death recording in primary care EHRs may be incomplete or differ from Office for National Statistics (ONS) death registrations. We used OpenSAFELY-TPP to assess the completeness and concordance of death recording and provide recommendations for using date-of-death information. Methods: Using linked primary care EHRs and ONS death registrations, we assessed whether ONS-registered deaths from 2020-2025 had a primary care date of death and, where present, calculated the difference between dates. Where a primary care date was absent, we assessed death-related SNOMED CT codes. Analyses were conducted overall and by year, population subgroup, and general practice. We also examined GP registration end dates and primary-care-recorded deaths without a corresponding ONS record, including monthly patterns near the data extraction date. Results: Among 1,409,275 ONS-registered deaths, 88% had the same date recorded in primary care and 8% had no corresponding primary care date. Among 1,324,995 deaths recorded in primary care, <2% had no corresponding ONS record. Deaths recorded in only one source were more frequent among people aged <45 years and those from Mixed, Asian or Asian British, Black or Black British, and Chinese or Other ethnic groups. ONS-only dates were also more frequent in London and the West Midlands. Primary-care-only deaths increased close to date of data extraction, reaching 7% in February 2026. Same-day GP deregistration increased from 9% in 2020 to 85% in 2025. Conclusions: Death recording in primary care EHRs showed high completeness and concordance with ONS registrations, but discrepancies remained for recent deaths and some population groups. Data recency and population-specific completeness should therefore be considered when using linked mortality data for research.

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Post-Initiation Care Patterns and Weight Loss With Semaglutide and Tirzepatide for Obesity in Clinical Practice

Yang, H.; Kim, C.; Ross, J. S.; Huang, C.; Choi, K.; Kang, B.; Arun, A.; Tang, H.; Chen, Y.; Xu, H.; Sharifi, M.; Li, Z.; Krumholz, H.; Lu, Y.

2026-10-06 cardiovascular medicine 10.64898/2026.10.04.26364715 medRxiv
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Abstract Background: Randomized trials show substantial weight loss with semaglutide and tirzepatide under structured care, but little is known about whether patients in routine practice continue therapy, reach a maintenance dose, and have their weight measured. Objectives: To describe the first year after initiation of semaglutide or tirzepatide for obesity, including care patterns, maintenance-dose attainment, weight documentation, and total body weight loss (TBWL). Methods: This retrospective cohort study used Epic Cosmos, an electronic health record network of >350 US health systems, to identify adults with obesity and without diabetes who initiated injectable semaglutide or tirzepatide in 2024. Outcomes over 12 months included prescribing persistence, discontinuation, switching, add-on therapy, and reinitiation; attainment of Food and Drug Administration (FDA)-labeled maintenance doses; availability of follow-up weight; and TBWL across progressively restricted populations. Results: Among 743,153 adults (60.1% semaglutide; mean age, 48.5 years; 72.5% female), 12-month prescribing persistence was 29.9% for semaglutide and 35.9% for tirzepatide. FDA-labeled maintenance-dose attainment was 28.3% and 55.0%, respectively, and only 8.8% and 16.4% remained prescribing persistent at a maintenance dose with a recorded weight at 12 months. About half of initiators lacked a 12-month weight. Among all initiators, [&ge;]5% TBWL was documented in 25.6% (semaglutide) and 30.4% (tirzepatide), rising to 51.9% and 61.9% among those with recorded weight, 66.1% and 79.5% among those also prescribing persistent, and 82.9% and 87.3% among those further at a maintenance dose. Conclusions: In routine practice, most patients initiating semaglutide or tirzepatide did not remain on therapy, reach a maintenance dose, and have weight documented through the first year. Documented weight loss was greatest among those completing each step of care, suggesting continuation, dose escalation, and monitoring as targets for improvement.

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Understanding clinician engagement with electronic health records: a mixed-methods study of structured data entry using the Theory of Planned Behaviour

Boustani, S.; Staras, C.; Rich, A.; Wilson, A.; Griffin, A.

2026-10-11 health informatics 10.64898/2026.10.08.26365036 medRxiv
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Background: Electronic health records (EHRs) are central to NHS clinical practice, and the value of the data they hold depends on clinicians entering structured data. Structured data entry (SDE) is nonetheless used inconsistently, and most evidence comes from US settings documenting barriers rather than the mechanisms interventions must target. This is, to our knowledge, the first study to apply the Theory of Planned Behaviour (TPB) to SDE, to examine SDE behaviour among UK NHS doctors, and to apply corpus linguistics to clinicians' free-text accounts of EHR use. Methods: A two-part mixed-methods study was conducted at a large NHS teaching hospital in central London using the Epic EHR. Study 1 was a cross-sectional survey of non-consultant grade doctors comprising the System Usability Scale (SUS), a purpose-designed TPB questionnaire, and two open-text questions analysed using corpus linguistics. Study 2 was an Interpretative Phenomenological Analysis (IPA) of semi-structured interviews with six resident doctors. Results: Eighty-three doctors responded; 65 completed the SUS and 49 the TPB questionnaire. Mean SUS score was 62.1 (95% CI 58.3-65.9), below the benchmark of 68 and equivalent to a grade of "D". Structured features were used markedly less often than narrative notes. TPB constructs explained 56% of the variance in intention (F(3,45) = 18.95, p < .001); attitudes (p = .003) and subjective norms (p = .009) predicted intention independently, whereas perceived behavioural control did not (p = .14). Intention predicted self-reported use of problem lists, event-specific templates and standardised documents, but not narrative notes. Corpus analysis identified time pressure and interface friction as dominant barriers. IPA generated four themes: structured documentation as cognitive relief; as fragile collective infrastructure; as a practice clinicians are expected to perform but not enabled to learn; and as a format that can flatten clinical reasoning. Conclusions: Engagement with SDE is driven principally by attitudes and social norms rather than by perceived control, and the barriers clinicians describe arise from the intersection of interface design, training, team norms and institutional expectation. Interventions addressing usability alone are unlikely to succeed: sustained change requires team-level normative reinforcement, specialty-relevant training that explains both how and why, and systems that preserve space for clinical narrative. Keywords: Electronic health records; structured data entry; Theory of Planned Behaviour; System Usability Scale; Interpretative Phenomenological Analysis; corpus linguistics; clinical documentation; data quality; NHS

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Remission of Type 2 Diabetes in Linked Health Records: Uncommon, Short-Lived, and More Often Ended by Treatment Restart Than by Rising HbA1c

Lobelo, F.; Durieux, J.; Kim, D. S.; Colovos, C.

2026-10-16 endocrinology 10.64898/2026.10.14.26365480 medRxiv
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Objective: To estimate how often remission of type 2 diabetes is recorded in routine care, how long it lasts, and what ends it, separating a return of hyperglycemia from a restart of treatment. Research design and methods: We studied 136,781 adults aged 18 years or older with laboratory confirmed type 2 diabetes in the Protege linked electronic health record (EHR) and claims database. The 96,817 adults with glucose-lowering treatment recorded at or before cohort entry formed the primary (previously treated) cohort; 39,964 adults with no treatment recorded at entry were analyzed in parallel. Remission required two HbA1c values <6.5%, 90 to 365 days apart, the first at least 3 months after all glucose-lowering drugs were discontinued, with no therapy recorded between them. After remission we followed glycemic relapse (HbA1c over 6.5%) and treatment restart (a new outpatient prescription or dispensed fill) separately, with death as a competing event (Aalen Johansen). Results: Remission was documented in 4.33% of previously treated adults cohort and 15.57% in the cohort of untreated adults at entry. Five-year cumulative incidence (Aalen Johansen) was 3.82% (95% CI 3.69 ;3.93) and 13.27% (12.90;13.59) in each cohort, respectively. Remission was less common with greater baseline treatment burden: exploratory adjusted 5-year incidence was 4.65% in adults with 1 glucose-lowering class with a treatment episode recorded at or before entry, 3.62% with two, 2.69% with three, and 2.02% with four or more such drugs.. The Median Kaplan Meier duration of first remission was 226 days (IQR 93 to 855) in previously treated adults and 371 days (166 to 1,027) in adults untreated at entry; 37.9% (treated cohort) and 23.1% (untreated cohort) of episodes had ended by 152 days. Among remission episodes that had ended, median duration was 159 days (71 to 362) and 265 days (129 to 565) for the treated and untreated at entry cohort, respectively. Within 5 years of remission in previously treated adults, the first event ending remission was glycemic relapse in 31.94%, treatment restart in 47.83%, and death in 4.65%.Treatment restart was about 1.5 times as common as glycemic relapse as the first event ending remission. A second remission followed within 5 years in 19.53% of previously treated and 24.10% of untreated remitters. Conclusions: Recorded remission was uncommon and short-lived, and it ended more often with a treatment restart than with a rise in HbA1c. Studies of remission in real-world data should report relapse and restart separately and state how they confirm remission and establish that treatment stopped.

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Medicine carbon footprinting across National Health Service trusts in England, 2021-2024: a longitudinal study using Freedom of Information requests

Taylor, H.; Rahman, N.

2026-10-12 health systems and quality improvement 10.64898/2026.10.09.26365120 medRxiv
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Introduction Medicines account for 20% of the National Health Service (NHS) carbon footprint, but it is unclear how consistently they are measured by individual NHS trusts. This study assessed medicine carbon footprint (MCF) practices across NHS trusts in England and whether these changed between 2021 and 2024. Methods Freedom of Information requests were sent to NHS trusts about MCF practices in 2021 and 2024. Responses were analysed to determine the proportion of trusts calculating MCFs, the medicines included and the emission factors used for spend-based calculations. Reported spend-based factors were compared with the median factor for each year to assess the effect of factor choice on MCFs. Results Of 196 trusts included in analysis, 178 (91%) responded for 2021 and 182 (93%) for 2024. Among responding trusts, 30 of 178 calculated MCFs in 2021 compared with 46 of 182 in 2024. Spend-based medicine footprinting increased from 19 trusts in 2021 to 31 in 2024. Ten different factors were used by 15 trusts in 2021 and 13 by 21 trusts in 2024. Reported factors ranged from 31% below to 258% above the median in 2024. Conclusions Medicine carbon footprinting remained uncommon, with only one-quarter of responding NHS trusts calculating a footprint in 2024. Among trusts using spend-based methods, wide variation in emission factors produced substantially different estimated MCFs. Clear national guidance on spend-based methodology could improve consistency in the short term, while greater use of standardised product-level approaches may better support medicine decarbonisation over time.

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How healthcare professionals manage uncertainty around hormone replacement therapy (dis-)continuation: the TAPER qualitative Study

Hillman, S.; Jones, L.; Kuypers, N.; Molloy, E.

2026-10-15 sexual and reproductive health 10.64898/2026.10.14.26365532 medRxiv
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Abstract Many women experience menopausal symptoms after stopping hormone replacement therapy (HRT). An evidence gap remains regarding how women and healthcare professionals (HCPs) make decisions about discontinuing and restarting HRT. Aim To explore experiences of HCPs that support women when they discontinue and restart HRT. Design and setting Qualitative study with HCPs working in NHS primary care. Method Semi-structured interviews with HCPs (n = 15) conducted between October 2025 and March 2026. A preliminary coding template was created using the discussion guide as a framework. Each interview was then coded inductively against the template which developed iteratively. Team based discussion helped refine codes into themes and sub-themes, and a subsequent conceptual model was created. Results The model describes HCPs experiences of supporting women to discontinue HRT as an iterative process characterised by uncertainty. Discussions about discontinuation were commonly prompted by changes in clinical risk or annual HRT review, but decisions about whether and when to stop also depended on womens symptoms, side effects, life stage and readiness. HCPs described agreeing an individualised discontinuation strategy, providing support during the process, and reviewing women after discontinuation to consider alternative treatments or, where appropriate, restarting HRT. Conclusion HCPs recognise the importance of readiness to discontinue and that decision making should be woman led, with HCP support, clear practice guidance and opportunities to revisit treatment. Further research is needed to support women weigh up their personalised risk and benefit of continuing/discontinuing and identify discontinuation strategies that limit resurgent symptoms.

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Reliability and accuracy of medication-based performance measures for assessment of outpatient cardiology clinicians

Chow, C.; Gunzburger, E.; Wilson, C.; Salahuddin, T.; Hess, P. L.; Essien, U.; Rodriguez, F.; Yang, K.-C.; Ziaeian, B.; Doll, J. A.

2026-10-02 cardiovascular medicine 10.64898/2026.09.29.26364366 medRxiv
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Background: Multiple performance measures are used to assess the management of common cardiovascular conditions, such as coronary artery disease (CAD), heart failure with reduced ejection fraction (HFrEF), and atrial fibrillation (AF). These measures are sometimes used to assess individual clinicians, despite lack of evidence of reliability and accuracy. We used national Veteran Affairs (VA) data to test medication-based performance measures for assessment of clinician performance in outpatient cardiology care. Methods: This retrospective study examined VA cardiology clinician/Veteran dyads from 2017-2023 to evaluate 10 medication-based performance measures for CAD, HFrEF, or AF with elevated stroke risk. Achievement of each performance measure was defined as an active prescription of an indicated medication for each eligible patient encounter, summarized at the clinician level. Reliability was calculated using the beta-binomial method. A Bayesian causal model was used to assess the impact of case complexity on performance measure achievement. Finally, we performed peer review of a subset of cases (n=952) to assess the accuracy of three representative performance measures. Results: Of 456,071 unique cardiology encounters, 312,331 included CAD, 224,599 included HFrEF, and 178,678 included AF. These patients were treated by 1,043 cardiology clinicians. Median performance measure achievement ranged from 0.23 (SGLT2i for HFrEF) to 0.99 (beta blocker for HFrEF). Measure reliability varied from 0.63 to 0.90. Case complexity did not significantly affect performance measure achievement. Using peer review as the gold standard, accuracy was poor to moderate (balanced accuracy 0.51-0.73), and measures underestimated performance relative to peer review. Conclusions: Ten medication-based performance measures for CAD, HFrEF, and AF can be efficiently measured using electronic health record data, and most have sufficient reliability to support clinician benchmarking and the identification of potential care gaps. However, suboptimal accuracy compared with a peer review indicates that these measures may be insufficient as a standalone assessment of clinician quality.

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Learning to integrate? Multimorbidity, chronic care and health system adaptation in post-USAID Zimbabwe

Mundoga, F.; Choga, K.; Webb, K.; Mangisi, P.; Tsvangirai, S.; Makore, V.; Katsidzira, A.; Gwanzura, C.; Apollo, T.; Chimbetete, C.; Mhlanga, T.; Chimberengwa, P.; Chinyanga, T. T.; Dhodho, E.; Dixon, J.

2026-09-29 primary care research 10.64898/2026.09.28.26364151 medRxiv
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Multimorbidity exposes tensions between complex health needs and health systems historically organized vertically around single diseases. While integrated chronic care has become a policy priority for many low- and middle-income countries, responses remain constrained by disease-specific configurations of knowledge, policy and practice. The USAID cuts represent a critical rupture in these arrangements, exposing dependencies while creating opportunities for integration, institutionalisation and local ownership. We examined challenges and opportunities for multimorbidity-responsive primary healthcare through a Learning Health System (LHS) lens, focusing on how information, deliberation, and action shape learning and adaptation processes in Zimbabwe during this period of transition. We conducted an ethnographic study in two urban metropolitan centers in Zimbabwe between October 2025 and February 2026, using patient journey mapping (n=23), participant observation, and in-depth interviews with healthcare workers, patients, decision-makers, health information specialists, and technical partners (n=19). We analyzed data thematically using an iterative framework informed by LHS concepts. Participants widely recognized multimorbidity as an increasingly common feature of primary care, yet care remained constrained by systems organized around individual diseases. Fragmentation was evident not only in clinical pathways but also in the information, accountability, and decision-making architectures through which health priorities were recognized and acted upon. At the same time, frontline providers routinely adapted care around patients' multiple conditions, revealing capacity for more integrated and person-centered approaches. Existing HIV platforms, including differentiated service delivery models and regional learning networks, were frequently identified as foundations for broader chronic care integration. These findings suggest that advancing multimorbidity-responsive care requires more than service integration; it requires strengthening the learning architectures through which health priorities are defined, knowledge is generated, and action is coordinated.

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Patterns of GLP-1 Receptor Agonist Initiation Compared With Other Glucose-Lowering and Anti-Obesity Therapies Among Older Adults

Brooks, J. D.; Donahue, M. A.; ElHassan, A.; Tian, J.; Hernandez-Diaz, S.; Blacker, D.; Estiri, H.; Haas, J. S.; Moura, L. M. V. R.

2026-10-05 endocrinology 10.64898/2026.09.29.26364340 medRxiv
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Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have rapidly expanded from primarily glucose-lowering agents for type 2 diabetes (T2D) to therapies used across diabetes, obesity, and cardiometabolic disease. Prescribing has risen sharply since 2018, especially with the broader uptake of semaglutide-based products. Still, real-world initiation patterns remain incompletely characterized in older adults with varying levels of cognitive vulnerability and frailty. Methods: We analyzed treatment patterns of GLP-1RA use in a retrospective cohort of adults aged >=65 years with T2D in a regional healthcare system from 2018 to 2026. We describe the demographic and clinical characteristics of new initiators of GLP-1RAs compared with initiators of alternative therapies, including sodium-glucose cotransporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i). We analyzed a sub-cohort of patients to identify the prevalence of baseline cognitive concerns using a large language model (LLM). We used a LASSO logistic regression to identify important predictors of GLP-1RA initiation compared to other therapies. Results: Of 58,754 adults aged 65 years or older with T2D, 5,095 initiated GLP-1RA, 5,483 initiated a SGLT2 inhibitor, and 1,516 initiated a DPP-4 inhibitor. GLP-1RA initiators were younger (mean 75.2 [SD 4.9] vs 77.7 [6.0] and 79.5 [7.1] years) and less often aged 80 years or older (17.7% vs 35.0% and 47.6%). The largest difference across groups was adiposity: mean BMI was 33.8 (6.2) vs 29.7 (5.7) and 28.6 (5.6) kg/m2 (SMD 0.592), with a BMI of 30 kg/m2 or higher in 72.1% vs 41.9% and 34.0%. Glycemic control was similar (mean HbA1c 7.46% vs 7.38% and 7.70%; SMD 0.165). GLP-1RA initiators were younger; more likely to be overweight; had lower average comorbidity index; and less dementia, heart failure, and renal disease than those initiating alternative therapies. GLP-1RA initiators had fewer hospitalizations 1-year prior to drug initiation. In a LASSO model, BMI greater than 27 kg/m2 was the strongest predictor of GLP-1RA initiation (positive), followed by baseline congestive heart failure (negative) and baseline hospitalization (negative). Conclusion: In this cohort of older adults, those with T2D who initiated GLP-1RAs were younger and had less comorbidities at baseline compared to initiators of other T2D therapies. Overweight BMI was the strongest predictor of GLP-1RAs initiation, whereas baseline HbA1c was similar across groups, suggesting that the decision to start GLP1-RA is more influenced by adiposity than glycemic control. Our analysis of real-world prescribing patterns appear to be in alignment with guidelines for Type II diabetes treatment1, which recommend GLP-1RA treatment for glucose lowering and weight management and SGLT2 treatment in those with risk of cardiovascular disease or heart failure.

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Can we Generate and Validate a Pregnancy Register for Research in the UK Greater Manchester Care Record Database Using Routine Primary Care Records

Cornett, C.; Tilston, G.; Martin, G.; Palin, V.

2026-10-02 obstetrics and gynecology 10.64898/2026.09.30.26364393 medRxiv
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Background: The Greater Manchester Care Record (GMCR) integrates health and social care data for 2.8 million individuals. While it contains maternity information, identifying individual pregnancies, including timing and outcomes, is complex due to variations in healthcare interactions and recording practices. This study develops open-source code to create a pregnancy register within the GMCR using diagnosis- and procedure-based algorithm established in other databases. Methods: 1,448 maternity SNOMED clinical codes identified pregnancy-related primary care records among women aged 14-49 years between March 2012 and August 2023. Codes were grouped by pregnancy outcome, with a hierarchical ruling approach where multiple outcomes appeared within one episode. Pregnancy start dates were derived from hierarchical coded events or imputed using biologically plausible duration based on outcome type. Internal validation compared GMCR register episodes against Hospital Episode Statistics (HES) hospital maternity admissions; external validation compared outcome rates against published UK estimates. Results: The algorithm was developed across 379,832 women, identifying 880,926 pregnancies. Internal validation showed nearly half of register deliveries had a corresponding HES record, with a positive predictive value (PPV) of 48.1%and a median date difference of 17 days (IQR 1-30). External comparison revealed live birth (927.8 vs. 995.6 per 1,000 deliveries) and stillbirth (2.12 vs. 3.9 per 1,000 births) rates close to national estimates but a notable discrepancy for miscarriage (8.00 vs. 15.3 per 100 pregnancies) and termination of pregnancy (5.36 vs. 25.1 per 1,000 women). Demographic alignment was strong for maternal age (31 vs. 29.8 years) and deprivation (IMD10 median: 3 vs. 2.6), though ethnic minority representation was expectedly higher in the GMCR (37.0% vs. 28.7%). Conclusions: This pregnancy register enriches the GMCR for maternal health research, enabling more comprehensive and regionally tailored studies to inform healthcare delivery and policy. This work represents an important first step in developing a scalable, open-source algorithmic tool to support pregnancy research across diverse populations. By making the code openly available, it can be adapted for use in federated data environments, enhancing reproducibility and collaboration.

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Evaluating a Clinical Decision Support System for Chronic Pain Management: A Per-Protocol Analysis

McCord, E.; Blackburn, J.; Holmes, A. M.; Apathy, N. C.; Grout, R. W.; Harle, C. A.; Mazurenko, O.

2026-10-09 primary care research 10.64898/2026.10.07.26364970 medRxiv
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Background: Clinical decision support (CDS) systems may improve chronic pain management by providing guideline-based recommendations within clinical workflows. However, low clinician use can limit their effectiveness. Understanding the association between CDS use and guideline-recommended care may help distinguish implementation challenges from limitations in CDS functionality. Objective: To estimate the association of OneSheet, a CDS system for chronic pain management, and guideline-recommended care when the system was used during patient encounters. Methods: We conducted a per-protocol secondary data analysis of data from a pragmatic randomized clinical trial conducted from October 2020 to May 2022 across 25 primary care clinics at 2 academic health systems in Indiana and North Carolina. The parent trial enrolled 137 primary care clinicians. This analysis included 145511 eligible chronic pain encounters and 15480 long term opioid therapy (LTOT) encounters that occurred after OneSheet implementation. OneSheet use at a patient encounter was the exposure of interest. Propensity score matching was used to create comparable groups of encounters with and without OneSheet use. Outcomes included documentation of pain-related goals, documentation of pain and function using the Pain, Enjoyment of Life and General Activity (PEG) scale, prescription drug monitoring (PDMP) review, urine drug screening (UDS) orders, and naloxone orders. Results: OneSheet was used in 959 of 145511 chronic pain encounters (0.7%) and 582 of 15480 LTOT encounters (4.0%). In matched analyses, OneSheet use was associated with increased documentation of pain-related goals (relative risk (RR)=11.70 (95% CI 4.25-32.50) and PEG score documentation (RR=9.70 (95% CI 4.14-22.31). Among LTOT encounters, OneSheet use was associated with increased UDS ordering (RR=1.52 (95% CI 1.40-1.65) and PDMP review (RR=1.06 (95% CI 1.03-1.09), but decreased naloxone ordering (RR=0.13 (95% CI, 0.02-0.90). Conclusions: OneSheet use was associated with several guideline-recommended chronic pain management actions, suggesting that they system may support care quality when clinicians use it. However, use was rare, indicating that increasing routine use through better workflow integration may be necessary to achieve population-level improvements in chronic pain care.

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Electronic Health Record Coding of Self-Reported Diagnoses in the All of Us Research Program

Asiaee, A.; Aryan, K.

2026-10-20 health informatics 10.64898/2026.10.18.26365863 medRxiv
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Importance: Conditions that are hard to diagnose, several more common in women, may be missing from electronic health records (EHRs), hiding patients from research cohorts and case finding. Objective: To measure how often the EHR contains a diagnosis code for chronic conditions that participants report, and to compare this with national survey benchmarks. Design, Setting, and Participants: This cross-sectional study used the All of Us Research Program Registered Tier Dataset v9. Participants were adults with EHR visits in both 12-month periods from July 2021 to June 2023 who completed a health history survey. We analyzed the data in October 2026. Exposures: Self-reported clinician diagnosis of 10 conditions with ongoing visits or treatment, as well as sex at birth, race and ethnicity, age, and years of EHR records. Main Outcomes and Measures: Share of participants reporting current care who had a qualifying diagnosis code, alone and relative to hypertension and type 2 diabetes, and the ratio of age-standardized coded shares to national survey prevalence. Results: Of 161,480 respondents, 114,610 (73,870 female [64.5%], median [IQR] age 63 [50-72] years) had at least 5 years of EHR records before the survey. Among those reporting current care, 84.6% (95% CI, 84.2%-85.0%) with hypertension and 87.0% (95% CI, 86.5%-87.6%) with type 2 diabetes had a code, compared with 41.3% (95% CI, 38.9%-43.8%) for endometriosis, 39.4% (95% CI, 34.3%-44.8%) for Lyme disease, and 24.4% (95% CI, 23.2%-25.6%) for chronic fatigue. Counting ICD-9-CM and other mapped codes, 55.3%, 51.5%, and 28.3%, respectively, had any qualifying record. Women had lower coded shares than men for hypertension, type 2 diabetes, obesity, depression, and anxiety (crude ratios 0.93-0.96, within-health-system ratios 0.98-1.02) and higher shares for migraine and fibromyalgia (within health systems, 1.11 [95% CI, 1.07-1.15] and 1.41 [95% CI, 1.29-1.57]). Age-standardized coded shares among active patients were 1.1 to 2.4 times national prevalence of the same self-reported diagnoses. Conclusions and Relevance: In this cross-sectional study, fewer than half of participants reporting ongoing care for chronic fatigue, Lyme disease, or endometriosis had a qualifying ICD-10-CM code. Linking each participant's report to their own record measured this gap directly.

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Timing matters: when do primiparous and multiparous pregnant women initiate folic acid supplementation, and who initiates it too late?

Ebong, U.; Given, J.; Casey, F.; Loane, M.; Dolk, H.

2026-09-27 public and global health 10.64898/2026.09.25.26363991 medRxiv
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Background: Women are recommended to take folic acid supplements (FAS) periconceptionally to prevent neural tube defects, but the low levels of FAS uptake are poorly understood. This study aimed to determine how parity, pregnancy planning and other maternal factors affect the timing of FAS initiation. Method: We used data from a representative sample of 966 pregnant women from the Northern Ireland Baby Hearts study. Questionnaire responses on health behaviours, including FAS, were linked to maternity and area-based deprivation data. Logistic regression assessed determinants of FAS initiation preconception. Time-varying Cox regression assessed associations between initiation postconception and pregnancy-related milestones. Results: Forty-one per cent of women initiated FAS preconception. Lower odds of preconception initiation were associated with multiparity (adjusted OR 0.47 (0.32 to 0.68)), unplanned pregnancy (adjusted OR 0.08 (0.05 to 0.13)), deprivation and consuming a low folate diet. Higher odds were associated with fertility treatment and previous pregnancy loss. Forty-seven per cent of women initiated FAS postconception, mainly after pregnancy recognition (median 5 weeks), including 34.1% of those who planned their pregnancy. For primiparous women with unplanned pregnancies, the first health service contact (median 7 weeks) further increased FAS initiation. Conclusion: Many women, even multiparous women with previous pregnancy experience and women who planned their pregnancies, are initiating FAS after pregnancy recognition. This shows awareness of FAS benefits, but is too late to prevent neural tube defects. Public health interventions need to go beyond awareness to address motivation and opportunity for FAS, and pay more attention to multiparous women.

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No Field for Lactation: Inferring Lactation Status From US Commercial Claims to Describe Postpartum Medication Dispensing

Krutsch, K.; Appiah, D.

2026-09-29 epidemiology 10.64898/2026.09.23.26363728 medRxiv
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Purpose Lactation status is not recorded as a discrete data element in U.S. administrative claims databases, limiting research on lactation in health databases. We developed a claims-based phenotype to identify periods of probable lactation and used it to describe medications dispensed to lactating women enrolled in a national health plan. Methods This retrospective cohort study used data from the 2012-2014 Merative MarketScan Commercial Claims Database. Deliveries were identified by diagnosis-related group classification system. Lactation windows ran from the delivery date to the date of the last surrogate lactation indicator, such as breast pump and supply codes, the encounter code for supervision of a lactating mother, and mastitis. New prescriptions filled within a window were characterized by therapeutic group, prescriber type, lactation risk category, and availability of published lactation data. Results Of 566,284 women with a single delivery, 84,679 were determined to be lactating using the developed algorithm based on maternal phenotype. The median length of assignable lactation window was 17 days (IQR 5-47). Windows most often closed on a breast pump claim (53.2%) or a postpartum visit code (28.2%). Among 158,471 new prescriptions filled during lactation, central nervous system agents (54.5%), anti-infectives (17.5%), and hormonal products accounted for > 80%. Combined oral contraceptives represented 8.2% of hormonal prescriptions during lactation against 29.0% among women of unknown status. Obstetricians wrote approximately one third of prescriptions filled during lactation windows. Conclusions Lactation can be identified in administrative claims using codes already present in the data, making national description of dispensing during lactation possible.

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Back to work MD - Experiences of internal medicine physicians returning to work after parental leave

Hasan, S.; Tang, G. H.; Van Bakel, T.; Fralick, M.; Sholzberg, M.

2026-10-08 medical education 10.64898/2026.10.06.26364854 medRxiv
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Background: Parenthood in medicine is an experience fraught with challenges that begin in the pre-conception phase and persist as physician-parents navigate their dual role. Methods: This study aims to understand the experiences of physician-parents (both childbearing and non-childbearing) returning to work after parental leave. Physicians, including residents, affiliated with the University of Toronto Department of Medicine internal medicine division who had a child within the last ten years were invited to participate in a self-administered electronic survey from June2022 to 30June 2023. Data were summarized using descriptive statistics. Results: Twenty-nine respondents took part in the survey; 79% were staff physicians while the remaining were trainees at the time of the survey. At the time their first child was born, 48% were staff members and 52% were trainees. The median duration of parental leave was 5 months (range 1-12 months). Among those for whom lactation was applicable, 76% reported that they continued their lactation efforts on returning to work, while 24% chose not to. Thirty five percent (35%, n=6/17) of respondents cited that they were not provided with duty hour modifications when required. Many respondents (46%) felt guilty about burdening their co-workers for requesting accommodations for childcare. When requested to rate their experiences of balancing their personal and professional lives on a scale of 1-10 (1 being impossible to maintain and 10 being extremely easy to maintain), most respondents (66%) chose a rating of 5 or less. Conclusion: This study supports previous findings that physician-parents face a myriad of challenges integrating their roles in medicine and parenthood. A change in culture is required to support and normalize parenthood for physicians and foster sustainability and productivity in academic medicine.

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Effects of Reimbursement Policy Change on Utilization of Injectable Semaglutide for Type 2 Diabetes and on Glycemic Control Among Discontinuers: A Danish Nationwide Cohort Study

Simonsen, E.; Ernst, M. T.; Christensen, D. H.; Kildegaard, H.; Soendergaard, J.; Thomsen, R. W.; Pottegaard, A.

2026-09-25 endocrinology 10.64898/2026.09.23.26363640 medRxiv
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Objectives. To evaluate the impact of reimbursement restrictions for glucagon-like peptide-1 receptor agonists (GLP-1RAs) for type 2 diabetes, introduced in Denmark in November 2024, on injectable semaglutide (Ozempic) utilization patterns and subsequent HbA1c changes among discontinuers. Design. Nationwide registry-based cohort study. Setting. Denmark. Participants. Adults treated with injectable semaglutide for diabetes (January 2018 to December 2025). Main outcome measures. We described temporal patterns in injectable semaglutide use before and after the policy change. Among semaglutide continuers after the policy change, we assessed whether continuation met a key criterion in the new policy: non-feasibility of sodium-glucose cotransporter 2 inhibitor use and high cardiovascular risk. We characterized semaglutide discontinuers around the policy implementation (March 2024 to November 2024) and subsequent treatment switches. Among discontinuers, we evaluated HbA1c changes and performed interrupted time series (ITS) analyses. Results. Following the policy change, use of injectable semaglutide declined modestly before subsequently increasing. Among 61,120 individuals classified as semaglutide continuers, 27,143 (44%) were already using an SGLT2i. Of the remaining 33,977 (56%), only 1,862 (5.5%) met a key reimbursement criterion (i.e., non-feasibility of SGLT2i use and high cardiovascular risk). Among 79,305 individuals with a semaglutide fill between March 2024 and November 2024, 22,096 (28%) were classified as discontinuers. Within six months, ~40% of discontinuers switched to other glucose-lowering therapies, most commonly SGLT2is (24%). 37% of discontinuers later reinitiated semaglutide. Among individuals with an on-treatment HbA1c measurement (within 12 months before their last semaglutide fill) and an off-treatment HbA1c measurement (6-12 months after their last semaglutide fill) (n=13,017), mean HbA1c increased from 49 to 57 mmol/mol (mean change +7.4 mmol/mol, 95% CI 7.2-7.6). ITS analysis showed that HbA1c increased by 5.9 mmol/mol (95% CI 5.1-6.7) at six months post-discontinuation, which attenuated to 3.1 mmol/mol (95% CI 2.2-4.1) at 12 months; raw monthly means (not included in the ITS model) suggested this persisted through 18 months. Conclusions. Following the policy change, population-level use of injectable semaglutide declined modestly before increasing again. Most discontinuers did not initiate another glucose-lowering therapy and experienced an increase in HbA1c that did not fully return to pre-discontinuation levels during follow-up.