BACKGROUND:Individuals of Black heritage comprise 6.2% of the General Practice workforce in the UK. Representation is even lower in Primary Care Research. The understanding of why this misrepresentation exists is limited. We explored the representation of researchers of Black heritage at various career stages within primary care, alongside factors influencing retention and career advancement. METHODS:Semi-structured interviews were conducted with 18 researchers of Black heritage and 7 primary care senior academic leaders (current or former heads of primary care departments in UK universities). Interviews explored representations within academic primary care, researcher career journeys, barriers and enablers to progression, and recommendations for improving diversity in the UK's primary care research workforce. Interviews were digitally audio recorded, transcribed and analysed thematically. RESULTS:All participants recognised significant underrepresentation of researchers of Black heritage in primary care research. Key barriers to career progression and retention included systemic and structural inequities, racism and exclusionary academic culture. Facilitators included proactive leadership, tailored training and support for researchers (including international scholars), mentorship, sponsorship and safe networking spaces. Participants offered recommendations to improve representation and career progression: training for leaders to recognise bias, discrimination and inequity, leadership development opportunities, tailored career support for researchers of Black heritage and targeted assistance for international researchers navigating UK academic systems. Visibility of Black role models in academic primary care was seen as essential to attracting and inspiring future researchers. CONCLUSION:These findings highlight key areas for change to foster a more inclusive and equitable research environment in primary care.

BACKGROUND:Women benefit from reduced fracture risk while using menopausal hormone therapy. However, information on risks after stopping menopausal hormone therapy is scarce and inconsistent, with no information on longer-term fracture risk as women age. We aimed to produce robust estimates of fracture risk among past users for the longest possible period after discontinuing therapy. METHODS:We did a nested case-control study using UK primary and secondary care data from the Clinical Practice Research Datalink, with the underlying cohorts CPRD GOLD and Aurum. Women, aged 40 years and older, registered with a primary care practice between Jan 1, 1998, and Feb 28, 2023, and with a first record for any fracture, were matched at the fracture index date with up to five female controls with no fracture history, who were of the same age and registered at the same general practice. Menopausal hormone therapy-related fracture risks were assessed using conditional logistic regression adjusted for demographics, family history, menopausal symptoms, comorbidities, and other medications. FINDINGS:In total, 648 747 women (500 692 from Aurum and 148 055 from GOLD databases) with a first fracture record during the study period were matched to 2 357 125 women with no previous or contemporaneous fracture record. Age of average fracture cases was 68·5 years (SD 14·0), 3·2% were recorded as being from minority ethnic populations, and about a quarter of patients were older than 80 years. 140 410 (21·6%) cases used menopausal hormone therapy for a median of 3·6 years (IQR 1·3-6·8) and 515 917 (21·9%) controls used it for a median of 3·9 years (1·4-7·3). Compared with never-use, overall fracture risk was reduced for current use (oestrogen-only odds ratio [OR] 0·76 [95% CI 0·74-0·78], oestrogen-progestogen OR 0·75 [0·73-0·76]), became higher 1-10 years after discontinuation (oestrogen-only OR 0·99 [0·98-1·01], oestrogen-progestogen OR 1·06 [1·05-1·08]), but was again lower for more than 10 years post-cessation (oestrogen-only OR 0·93 [0·91-0·94], oestrogen-progestogen OR 0·95 [0·94-0·96]). Risk levels varied by menopausal hormone therapy type and by duration of treatment. Estimated extra fracture cases per 10 000 women-years 1-10 years after oestrogen-progestogen treatment were equivalent to 14 cases for less than 5 years menopausal hormone therapy exposure and five cases for 5 or more years of exposure. However, for more than 10 years after discontinuation, we estimated three fewer fracture cases for those on oestrogen-progestogen therapy for less than 5 years exposure and 13 fewer fracture cases for those with 5 or more years of exposure. INTERPRETATION:We have observed an attenuation of fracture risk after discontinuing menopausal hormone therapy, which manifests after an initial sharp rise. Fracture risk generally increases with age, but after discontinuation of menopausal hormone therapy, fracture risk increases steeply, usually to above the levels of comparable never-users, and then rises less quickly relative to never-users to become again notably reduced by comparison in older age. Our findings provide information for researchers looking to improve fracture risk outcomes for women after discontinuing menopausal hormone therapy, and for doctors and their patients to consider before commencing or stopping menopausal hormone therapy, especially regarding expected steep post-discontinuation rises in fracture risk and periods of enhanced fracture risk. FUNDING:National Institute for Health & Care Research.

(Abstracted from Lancet 2024;404:1430–1443) About 1 in 8 women experience postnatal depression. In the United Kingdom, common perinatal mental disorders, including postnatal depression, are estimated to cost about £8.1 billion for each 1-year birth cohort.

OBJECTIVE:To characterize multinational trends and patterns of opioid analgesic prescribing by sex and age. DESIGN, SETTING, AND PARTICIPANTS:We studied opioid analgesic prescribing from 2001 to 2019 with common protocol using population-based databases from eighteen countries and one special administrative region. MAIN OUTCOME MEASURES:We measured opioid prescribing by geographical region, sex and age, estimating annual prevalent, incident, and nonincident opioid prescribing per 100 population with a 95% confidence interval (CI) and meta-analyzed the multinational and regional opioid prescribing with a random-effects model. Time trends were reported through average annual absolute changes, estimated using linear mixed models. We further explored the effect of sex and age on prevalent opioid prescribing in the multivariable analysis. RESULTS:Over 248 million individuals were included. Pooled multinational opioid prescribing prevalence was 9.0% amongst included countries/regions. Opioid prescribing prevalence in 2015 ranged from 2.7% in Japan to 19.7% in Iceland. Average annual absolute changes in opioid prescribing prevalence per year ranged from - 1.53% (95% CI - 2.06, - 1.00; United States Medicaid) to + 1.24% (95% CI 1.02, 1.46; South Korea). Pooled multinational incident opioid prescribing (4.9%; 95% CI 4.1, 5.9) was higher than pooled multinational nonincident opioid prescribing (3.7%; 95% CI 2.9, 4.8). The female sex and older age were associated with higher opioid prescribing. Main limitations of this study include the absence of data from study duration or individuals not covered by the data sources and the lack of information on medication adherence and indication. CONCLUSIONS:Opioid prescribing remains unbalanced across geographical regions; however, results suggest a tendency to convergence across countries/regions. Differences in opioid prescribing by sex and age were identified.

Background:Postnatal depression is more common in British South Asian women than white women in the United Kingdom. Despite empirical evidence suggesting the effectiveness of cognitive-behavioural therapy as a first line of treatment, little evidence is available regarding its applicability to different minority ethnic groups. Objectives:Determining the clinical and cost-effectiveness of a culturally adapted group psychological intervention (Positive Health Programme) in primary care for British South Asian women with postnatal depression compared with treatment as usual. Setting:General practices and children's centres in the North West, East Midlands, Yorkshire, Glasgow and London. Participants:British South Asian women meeting the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) depression criteria, aged 16 years or above, with infants up to 12 months. Design:A multicentre randomised controlled trial with an internal pilot and partially nested design to compare treatment as usual plus the Positive Health Programme with treatment as usual in British South Asian women with postnatal depression, with a qualitative study to examine the acceptability and feasibility of the intervention. Intervention:The Positive Health Programme, a culturally adapted group intervention based on the principles of cognitive-behavioural therapy delivered by facilitators over 12 sessions. Outcomes measures:The primary outcome was recovery from depression (Hamilton Depression Rating Scale ≤ 7) at end of intervention (approximately 4-6 months). Analysis of the primary outcome and the long-term follow-up (at 12 months) used a logistic random-effects model to estimate the odds ratio of caseness between treatments, adjusting for centre, severity of depression and education at baseline. Cost data were collected using an Economic Patient Questionnaire. Results:Seven hundred and thirty-two participants across four study centres were randomised by the Manchester Clinical Trials Unit. At 4 months, almost half of patients in the treatment (Positive Health Programme) group were recovered (138 or 49%), whereas 105 (37%) were recovered in the control (treatment as usual) group. By 12 months, the control (treatment as usual) and treatment (Positive Health Programme) group had over 50% recovery at 140 (54%) and 141 (54%), respectively. For the primary outcome, recovery from postnatal depression at end of intervention, we found a significant effect such that the odds of achieving recovery in the treatment group were almost twice as high compared to the treatment as usual group (odds ratio 1.97, 95% confidence interval 1.26 to 3.10). Between the two groups, there was no significant difference in the odds of recovery at 12 months (odds ratio 1.02, 95% confidence interval 0.62 to 1.66), highlighting a need for more intensive therapies and/or longer-term care plans for this group of patients. Qualitative results:The intervention was considered feasible and acceptable from the perspectives of Positive Health Programme participants, facilitators, and general practitioners. The findings suggest improved emotional and social support and an enhanced sense of well-being. Economic evaluation:Positive Health Programme implementation was estimated to cost an average of £408 per participant. The intention-to-treat analysis shows that the Positive Health Programme intervention costs £22,198 per quality-adjusted life-year gain. Positive Health Programme was cost-effective on average but with a substantial uncertainty: the probability that Positive Health Programme was cost-effective was 44% (65%) at the willingness to pay £20,000 (£30,000) per quality-adjusted life-year. The Positive Health Programme was highly cost-effective for those who attended 5-8 sessions, costing £9040 per quality-adjusted life-year. Limitations:The study sample limits generalisability with other ethnic minority groups, and the cost-effectiveness analysis did not explore recall bias. Conclusions:The results of this study provide robust evidence that the culturally adapted psychological intervention for postnatal depression in South Asian women is effective at the primary end point and acceptable to women. Future work:Further development of the Positive Health Programme intervention and evaluation, with longer-term outcome follow-ups and exploration of cost-effectiveness of remote delivery of the Positive Health Programme. Study registration:Current Controlled Trials ISRCTN10697380. Funding:This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/68/08) and is published in full in Health Technology Assessment; Vol. 29, No. 6. See the NIHR Funding and Awards website for further award information.

Background: Social deprivation is associated with higher cardiovascular disease (CVD) morbidity and mortality. We examined whether this is also observed in people with Familial Hypercholesterolaemia (FH). Methods: Subjects with FH and linked secondary care records in Hospital Episode Statistics (HES) were identified from UK Clinical Practice Research Datalink (CPRD) and the Simon Broome (SB) adult FH register. Cox proportional hazards regression estimated hazard ratios (HR) for composite CVD outcomes (first HES outcome of coronary heart disease, myocardial infarction, angina, stroke, transient ischaemic attack, peripheral vascular disease, heart failure, coronary revascularisation interventions (PCI and CABG)) in Index of Multiple Deprivation (IMD) quintiles. Results: We identified 4309 patients with FH in CPRD (1988-2020) and 2956 in the SB register. Both cohorts had considerably fewer subjects in the most deprived compared to the least deprived quintile (60 % lower in CPRD and 52 % lower in SB). In CPRD, the most deprived individuals had higher unadjusted HRs for composite CVD (HR 1.71 [CI 1.22-2.40]), coronary heart disease (HR 1.63 [1.11-2.40]) and mortality (HR 1.58 [1.02-2.47]) compared to the least deprived but these became insignificant after adjusting for age, sex, smoking and alcohol consumption. In the SB register, hazard ratios for composite CVD increased with increasing deprivation quintiles and remained significant after adjustment for age, sex, smoking and alcohol consumption (adjusted HR in quintile 5 vs quintile 1 = 1.83 [1.54-2.17]). Conclusions: Strikingly fewer individuals with FH are identified from lower socioeconomic groups, though the most deprived FH patients have the highest risk of CVD and mortality. In CPRD, this risk was largely explained by smoking and alcohol consumption, but not in the SB register. More effective strategies to detect FH and optimise risk factor management, are needed in lower socioeconomic groups.

Randomised controlled trials (RCTs) are widely regarded as the most powerful research design for evidence-based practice. However, recruiting to RCTs can be challenging resulting in heightened costs and delays in research completion and implementation. Enabling successful recruitment is crucial in mental health research. Despite the increase in the use of remote recruitment strategies and digital health interventions, there is limited evidence on methods to improve recruitment to remotely delivered mental health trials. The paper outlines practical examples and recommendations on how to successfully recruit participants to remotely delivered mental health trials. The Alpha Stim-D Trial was a multi-centre double-blind randomised controlled trial, for people aged 16 years upwards, addressing depressive symptoms in primary care. Despite a 6-month delay in beginning recruitment due to the COVID-19 pandemic, the trial met the recruitment target within the timeframe and achieved high retention rates. Several strategies were implemented to improve recruitment; some of these were adapted in response to the COVID-19 pandemic. This included adapting the original in-person recruitment strategies. Subsequently, systematic recruitment using postal invitations from criteria-specific search of the sites’ electronic health records was added to opportunistic recruitment to increase referrals in response to sub-target recruitment whilst also reducing the burden on referring sites. Throughout the recruitment process, the research team collaborated with key stakeholders, such as primary care clinicians and the project’s Patient and Public Involvement and Engagement (PPI/E) representatives, who gave advice on recruitment strategies. Furthermore, the study researchers played a key role in communicating with participants and building rapport from study introduction to data collection. Our findings suggest that trial processes can influence recruitment; therefore, consideration and a regular review of the recruitment figures and strategies is important. Recruitment of participants can be maximised by utilising remote approaches, which reduce the burden and amount of time required by referring sites and allow the research team to reach more participants whilst providing participants and researchers with more flexibility. Effectively communicating and working collaboratively with key stakeholders throughout the trial process, as well as building rapport with participants, may also improve recruitment rates.

Menopausal hormone therapy (MHT) is prescribed to women with severe symptoms of menopause. Various studies have demonstrated increased bone density and decreased fracture risk in women using MHT. The randomised controlled trials were, however, run over only relatively short time periods, and there is no reliable or consistent evidence about fracture risk after MHT discontinuation. The proposed nested case-control study aims to fill this gap. We will use CPRD (GOLD and AURUM) and HES data. Every woman 40 years or over with a diagnosis of first fracture between 1998 and 2022 (a case) will be matched by age and general practice to up to 5 female controls with no previous records of fracture at the time of the case diagnosis (index date). MHT exposure will be assessed using prescriptions for the different types of MHT treatment historically available from the NHS. Conditional logistic regression will estimate fracture risk associated with duration of use and gap after discontinuation of MHT. The findings will be adjusted for smoking status, body mass index, family history of dementia, medical conditions and events, other medications and contraceptive drugs. A number of sensitivity analyses will be run to address the limitations of the study.### Competing Interest StatementThe authors have declared no competing interest.### Funding StatementThis study was funded by School for Primary Care Research NIHR, #617### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:National Research Ethics Service Committee (NRES), for all purely observational research using anonymised CPRD data, eRap#22_002376I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesTo guarantee the confidentiality of personal and health information, only the authors can have access to the CPRD data during the study in accordance with the relevant licence agreements. CPRD linked data were provided under a licence that does not permit sharing.

Patients with rare genetic diseases frequently experience significant diagnostic delays. Routinely collected data in the electronic health record (EHR) may be used to help identify patients at risk of undiagnosed conditions. Long QT syndrome (LQTS) is a rare inherited cardiac condition associated with significant morbidity and premature mortality. In this study, we examine LQTS as an exemplar disease to assess if clinical features recorded in the primary care EHR can be used to develop and validate a predictive model to aid earlier detection. 1495 patients with an LQTS diagnostic code and 7475 propensity-score matched controls were identified from 10.5 million patients’ electronic primary care records in the UK’s Clinical Practice Research Datalink (CPRD). Associated clinical features recorded before diagnosis (with p < 0.05) were incorporated into a multivariable logistic regression model, the final model was determined by backwards regression and validated by bootstrapping to determine model optimism. The mean age at LQTS diagnosis was 58.4 (SD 19.41). 18 features were included in the final model. Discriminative accuracy, assessed by area under the curve (AUC), was 0.74, (95

Background Postnatal depression necessitates timely and effective interventions to mitigate adverse maternal and child outcomes in the short term and over the life course. British south Asian women with depression are often underserved and undertreated due to stigma, language barriers, and cultural barriers. This trial aimed to test the clinical efficacy of a culturally adapted, group cognitive behavioural therapy (CBT)-based intervention, the Positive Health Programme (PHP), delivered by non-specialist health workers for postnatal depression in British south Asian women. Methods This study was a randomised controlled trial, with culturally adapted recruitment and an internal pilot, comparing the PHP (intervention group) with treatment as usual (control group) in British south Asian women with postnatal depression. The study was conducted at five centres across the UK. Participants were aged 16 years or older, met the DSM-5 criteria for depression, and had infants aged 0-12 months. Randomisation (1:1) was stratified by centre, with a block size of 18, and was done through an independent remote telephone service. The PHP was delivered over 12 group sessions in 4 months. The primary outcome was recovery from depression (defined as a Hamilton Depression Rating Scale [HDRS] score <= 7) at 4 months after randomisation, and an assessment was also done at 12 months. Analysis was on an intention-to-treat basis including only participants with non-missing outcome data; we used a random-effects logistic regression model including fixed covariates for study site, baseline depression severity (HDRS score), parity, and years in education and a random coefficient for therapy group. This trial is registered with the ISRCTN (ISRCTN10697380). Findings Of the 9136 individuals approached for recruitment between Feb 8, 2017, and March 29, 2020, 4296 women were eligible for and consented to screening, among whom 732 screened positive and were randomly allocated: 368 (50%) to the PHP group and 364 (50%) to the control group. Participants were mostly of Pakistani (397 [55%] of 719 with available data), Indian (176 [24%]), or Bangladeshi ethnicity (127 [18%]), with an overall mean age of 314 years (SD 52), with their youngest infants having a mean age of 236 weeks (142). At 4 months from randomisation, the proportion of participants who showed recovery from depression on the HDRS was significantly higher in the PHP group (138 [49%] of 281) than in the control group (105 [37%] of 281; adjusted odds ratio 197 [95% CI 126-310]). At the 12-month follow-up, this difference was no longer significant (102 [95% CI 062-166]). Interpretation In British south Asian women with postnatal depression, a culturally adapted group CBT-based intervention could aid in quicker recovery from depression compared with treatment as usual. Further research is needed to identify how to sustain the treatment effect and establish strategies for scale-up.

Background Evidence suggests that coordination of care for people affected by rare diseases is poor. In order to improve the way that care is coordinated it is necessary to understand the preferences of people affected by these conditions, and providers. The aim of this study was to examine patient, parent and carer, and health care professional preferences for different attributes of care coordination for people affected by rare diseases. We conducted a discrete choice experiment using online surveys. There were no restrictions on participants in terms of rare conditions, demographic factors other than age, or geographical location within the UK. Choice scenarios were based on the following attributes: annual cost of attending appointments; access to health records; access to clinical expertise; support of a care coordinator; access to a specialist centre; and, the existence of a documented plan for emergency care. Data were analysed using alternative-specific conditional logit regression models. Results Valid responses were obtained from 996 individuals (528 patients, 280 carers, 188 health care professionals) between August and December 2019. All attributes significantly influenced the type of service respondents preferred. Patients, carers and health professionals’ preferences for care coordination were influenced by: the cost of attending appointments; access to health records; clinical expertise; role of care coordinators; access to specialist centres; and the existence of plan for emergency care. There were no statistically significant differences in the preferences between patients and carers. Preferences of health professionals differed to those of patients and carers. Both patients and carers selected responses which granted them a greater degree of autonomy in relation to the role of care coordinators, whereas health professionals preferred services where care coordinators had more autonomy. Health care professionals also expressed a stronger preference for a documented formal emergency plan to be in place. Conclusions The findings highlight that people value better coordinated care, in line with policy documents emphasising commitments to coordinated care for people affected by rare diseases. This study highlights the factors that could be included in service provision as ways of improving the coordination of care for people affected by rare diseases.