Health Institutions Research Articles

The association of HIV status with triple-negative breast cancer in patients with breast cancer in South Africa: a cross-sectional analysis of case-only data from a prospective cohort study

Breast cancer is the most common malignancy diagnosed among women in South Africa, with the aggressive triple-negative subtype comprising approximately 15% of breast cancers in this population. South Africa has the largest population of people with HIV in the world. This study aims to evaluate the association between HIV status and the proportion of patients with breast cancer with the triple-negative subtype. We did a cross-sectional analysis of case-only data from the South African Breast Cancer and HIV Outcomes (SABCHO) study, a prospective cohort study recruiting patients with newly diagnosed breast cancer at six public hospitals in South Africa. We analysed data from patients who enrolled in SABCHO between Jan 1, 2015, and Jan 18, 2022. Women aged 18 years or older with newly diagnosed and histologically confirmed invasive breast cancer were eligible. Participants were classified as HIV-positive or HIV-negative by use of an ELISA-based HIV test done at the time of enrolment. We developed multivariable logistic regression models to test for an association between HIV status and the proportion of triple-negative relative to non-triple-negative breast cancers while adjusting for demographic and reproductive risk factors. Of the 4122 patients enrolled in the SABCHO cohort within our study timeframe, 239 patients were excluded due to unknown breast cancer subtype (n=141), HIV status (n=97), or race (n=1). 3883 women with breast cancer were included in the study, of whom 637 (16·4%) had triple-negative breast cancer, 894 (23·0%) were HIV-positive, and 186 (4·8%) had triple-negative breast cancer and HIV. Triple-negative breast cancer accounted for 186 (20·8%) of 894 breast cancers among women who were HIV-positive and 451 (15·1%) of 2989 breast cancers among women who were HIV-negative (p<0·0001). In the fully adjusted logistic regression model, HIV-positive status was associated with an increased proportion of triple-negative breast cancer (adjusted odds ratio [OR] 1·39, 95% CI 1·12-1·74, compared with women who were HIV-negative). When compared with women who were HIV-negative, the association between HIV-positive status and the proportion of triple-negative breast cancer was strongest among the subgroup of women with a duration of HIV infection of 2 years or longer (1·57, 1·23-2·00) and those on antiretroviral therapy (ART; 1·47, 1·16-1·87). Patients with breast cancer and chronic HIV who are on ART are more likely to have triple-negative breast cancer than patients with breast cancer without HIV. This association is independent of age, race, and reproductive factors. US National Institutes of Health, University of the Witwatersrand, South Africa Medical Research Council Common Epithelial Cancers Research Center, Conquer Cancer Foundation, and Varmus Global Scholars Fund.

Determining health professional students' self-perceived cultural capability following participation in clinical placement with Aboriginal and Torres Strait Islander Peoples: A systematic review.

Collective evaluation of studies assessing students' self-perceived cultural capability following clinical placement is required to help inform future cultural capability training for both university and healthcare service environments. Therefore, the aim of this systematic review was to evaluate studies investigating health professional students' self-perceived cultural capability following participation in a clinical placement with First Nations Peoples. Electronic database searchers were conducted in MEDLINE, EMBASE, AMED, PsychINFO, Pubmed, CINAHL and Informit. Hand Searches of grey literature were conducted including Lowitja institute, Australian Indigenous HealthInfoNet, Menzies School of Health Research, Services for AustralianRural and Remote Allied Health, and the Australian Institute of Health and Welfare. Studies published in English that investigated health professional students' self-perceived cultural capability before and after clinical placement undertaken with First Nations people in Australia were eligible for inclusion. Two authors independently screened potentially eligible studies and performed quality appraisal and data extraction. A total of 14 studies were included (n = 307 participants). Studies included undergraduate students from podiatry, medicine, nursing, pharmacy, and mixed health professions. The results of this systematic review suggest that clinical placements in health services or settings for Aboriginal and Torres Strait Islander Peoples that involve elements of co-design are effective in increasing aspects of health professional students' self-perceived cultural capability. This outcome was consistent across studies regardless of the location of clinical placements (urban or rural), type of clinical placement (health setting or Community), or length of placement. The findings from this systematic review suggest that clinical placement in health services or settings for Aboriginal and Torres Strait Islander Peoples may contribute to increased self-perceived cultural capability in health professions graduates. However, the impact of the placements on the cultural safety of student-led care, from a First Nations perspective, remains to be established.

Early mental health intervention and supported self-care for LGBTQ+ young people in the UK: a mixed-methods study.

Lesbian, gay, bisexual, trans, queer/questioning, plus young people have a higher risk of poor mental health in comparison to cisgendered heterosexual young people, and they underutilise mental health services and support. In addition, there is a paucity of research conducted in United Kingdom examining mental health early intervention provision for lesbian, gay, bisexual, trans, queer/questioning, plus young people. To produce a model of what works for early intervention mental health support for lesbian, gay, bisexual, trans, queer/questioning, plus young people and increase understanding of lesbian, gay, bisexual, trans, queer/questioning, plus young people's access to, navigation of, and engagement with mental health support. This was a multi-methods theory-led case study evaluation with three distinct stages: (1) a meta-narrative review of existing literature to develop a theoretical framework to explain effective mental health support for lesbian, gay, bisexual, trans, queer/questioning, plus young people; (2) an online and offline service mapping exercise to locate current mental health early intervention support for lesbian, gay, bisexual, trans, queer/questioning, plus young people in the United Kingdom in order to produce a service typology; and (3) a theory-led case study evaluation of 12 case study sites selected from the service typology produced in stage 2, to establish the components of appropriate quality, early intervention mental health support for lesbian, gay, bisexual, trans, queer/questioning, plus young people. Stage 1 produced an interdisciplinary theoretical framework indicating that early intervention mental health support for lesbian, gay, bisexual, trans, queer/questioning, plus youth must prioritise addressing normative environments that marginalise youth, lesbian, gay, bisexual, trans, queer/questioning, plus identities and mental health problems. Stage 2 mapping found 111 services, the majority in urban settings in England. There was an absence of mainstream National Health Service support that specifically addressed the needs of lesbian, gay, bisexual, trans, queer/questioning, plus young people. The majority of lesbian, gay, bisexual, trans, queer/questioning, plus youth mental health support was provided by voluntary/community organisations. Stage 3 case study evaluation found that an intersectional, youth-rights approach is the most appropriate way to deliver early intervention mental health support for lesbian, gay, bisexual, trans, queer/questioning, plus young people. Youth rights should underpin mental health support to address the multiple marginalisation, isolation and stigmatisation that lesbian, gay, bisexual, trans, queer/questioning, plus young people may experience and to enable them to make informed independent decisions about their own bodies and lives, and for the right to freedom of safe self-expression to be upheld. The model that we have produced contains 13 principles that are necessary to the provision of mental health support, and to improve access to, engagement with, and navigation of mental health services. In the United Kingdom, a rights-based approach to mental health service provision is not prominent. In addition, at the time of writing, lesbian, gay, bisexual, trans, queer/questioning, plus young people are facing active legislative and policy attacks on their human rights. This study provides the first large-scale theory-led evaluation of early intervention mental health support for lesbian, gay, bisexual, trans, queer/questioning, plus young people with common mental health problems. The resulting intersectional, youth-rights approach provides evidence on ways of improving lesbian, gay, bisexual, trans, queer/questioning, plus young people's mental health. Further research on the implementation of an intersectional, youth-rights approach to early intervention mental health support for lesbian, gay, bisexual, trans, queer/questioning, plus young people with mental health problems is required. This study is registered as PROSPERO CRD42019135722. This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 17/09/04) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 47. See the NIHR Funding and Awards website for further award information.

Polygenic and transcriptional risk scores identify chronic obstructive pulmonary disease subtypes in the COPDGene and ECLIPSE cohort studies

Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics. We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein-protein interaction networks and drug repurposing analyses between high-risk groups. We examined two high-risk omics-defined groups in non-overlapping test sets (n=1133 NHW COPDGene, n=299 African American (AA) COPDGene, n=468 ECLIPSE). We defined "high activity" (low PRS, high TRS) and "severe risk" (high PRS, high TRS) subgroups. Participants in both subgroups had lower body-mass index (BMI), lower lung function, and alterations in metabolic, growth, and immune signalling processes compared to a low-risk (low PRS, low TRS) subgroup. "High activity" but not "severe risk" participants had greater prospective FEV1 decline (COPDGene:-51mL/year; ECLIPSE:-40mL/year) and proteomic profiles were enriched in gene sets perturbed by treatment with 5-lipoxygenase inhibitors and angiotensin-converting enzyme (ACE) inhibitors. Concomitant use of polygenic and transcriptional risk scores identified clinical and molecular heterogeneity amongst high-risk individuals. Proteomic and drug repurposing analysis identified subtype-specific enrichment for therapies and suggest prior drug repurposing failures may be explained by patient selection. National Institutes of Health.

Genomic insights for personalised care in lung cancer and smoking cessation: motivating at-risk individuals toward evidence-based health practices

Lung cancer and tobacco use pose significant global health challenges, necessitating a comprehensive translational roadmap for improved prevention strategies such as cancer screening and tobacco treatment, which are currently under-utilised. Polygenic risk scores (PRSs) may further motivate health behaviour change in primary care for lung cancer in diverse populations. In this work, we introduce the GREAT care paradigm, which integrates PRSs within comprehensive patient risk profiles to motivate positive health behaviour changes. We developed PRSs using large-scale multi-ancestry genome-wide association studies and standardised PRS distributions across all ancestries. We validated our PRSs in 561,776 individuals of diverse ancestry from the GISC Trial, UK Biobank (UKBB), and All of Us Research Program (AoU). Significant odds ratios (ORs) for lung cancer and difficulty quitting smoking were observed in both UKBB and AoU. For lung cancer, the ORs for individuals in the highest risk group (top 20% versus bottom 20%) were 1.85 (95% CI: 1.58-2.18) in UKBB and 2.39 (95% CI: 1.93-2.97) in AoU. For difficulty quitting smoking, the ORs (top 33% versus bottom 33%) were 1.36 (95% CI: 1.32-1.41) in UKBB and 1.32 (95% CI: 1.28-1.36) in AoU. Our PRS-based intervention model leverages large-scale genetic data for robust risk assessment across populations, which will be evaluated in two cluster-randomised clinical trials. This approach integrates genomic insights into primary care, promising improved outcomes in cancer prevention and tobacco treatment. National Institutes of Health, NIH Intramural Research Program, National Science Foundation.

Collagenase injection versus limited fasciectomy surgery to treat Dupuytren's contracture in adult patients in the UK: DISC, a non-inferiority RCT and economic evaluation.

Dupuytren's contracture is caused by nodules and cords which pull the fingers towards the palm of the hand. Treatments include limited fasciectomy surgery, collagenase injection and needle fasciotomy. There is limited evidence comparing limited fasciectomy with collagenase injection. To compare whether collagenase injection is not inferior to limited fasciectomy when treating Dupuytren's contracture. Pragmatic, two-arm, unblinded, randomised controlled non-inferiority trial with a cost-effectiveness evaluation and nested qualitative and photographic substudies. Thirty-one National Health Service hospitals in England and Scotland. Patients with Dupuytren's contracture of ≥ 30 degrees who had not received previous treatment in the same digit. Collagenase injection with manipulation 1-7 days later was compared with limited fasciectomy. The primary outcome was the Patient Evaluation Measure score, with 1 year after treatment serving as the primary end point. A difference of 6 points in the primary end point was used as the non-inferiority margin. Secondary outcomes included: Unité Rhumatologique des Affections de la Main scale; Michigan Hand Outcomes Questionnaire; recurrence; extension deficit and total active movement; further care/re-intervention; complications; quality-adjusted life-year; resource use; and time to function recovery. Online central randomisation, stratified by the most affected joint, and with variable block sizes allocates participants 1 : 1 to collagenase or limited fasciectomy. Participants and clinicians were not blind to treatment allocation. Between 31 July 2017 and 28 September 2021, 672 participants were recruited (n = 336 per group), of which 599 participants contributed to the primary outcome analysis (n = 285 limited fasciectomy; n = 314 collagenase). At 1 year (primary end point) there was little evidence to support rejection of the hypothesis that collagenase is inferior to limited fasciectomy. The difference in Patient Evaluation Measure score at 1 year was 5.95 (95% confidence interval 3.12 to 8.77; p = 0.49), increasing to 7.18 (95% confidence interval 4.18 to 10.88) at 2 years. The collagenase group had more complications (n = 267, 0.82 per participant) than the limited fasciectomy group (n = 177, 0.60 per participant), but limited fasciectomy participants had a greater proportion of 'moderate'/'severe' complications (5% vs. 2%). At least 54 participants (15.7%) had contracture recurrence and there was weak evidence suggesting that collagenase participants recurred more often than limited fasciectomy participants (odds ratio 1.39, 95% confidence interval 0.74 to 2.63). At 1 year, collagenase had an insignificantly worse quality-adjusted life-year gain (-0.003, 95% confidence interval -0.006 to 0.0004) and a significant cost saving (-£1090, 95% confidence interval -£1139 to -£1042) than limited fasciectomy with the probability of collagenase being cost-effective exceeding 99% at willingness to pay thresholds of £20,000-£30,000 per quality-adjusted life-year. At 2 years, collagenase was both significantly less effective (-0.048, 95% confidence interval -0.055 to -0.040) and less costly (-£1212, 95% confidence interval -£1276 to -£1147). The probability of collagenase being cost-effective was 72% at the £20,000 threshold but limited fasciectomy became the optimal treatment at thresholds over £25,488. The Markov model found the probability of collagenase being cost-effective at the lifetime horizon dropped below 22% at thresholds over £20,000. Semistructured qualitative interviews found that those treated with collagenase considered the outcome to be acceptable, though not perfect. The photography substudy found poor agreement between goniometry and both participant and clinician taken photographs, even after accounting for systematic differences from each method. Impacts of the COVID-19 pandemic resulted in longer waits for Dupuytren's contracture treatment, meaning some participants could not be followed up for 2 years. This resulted in potential underestimation of Dupuytren's contracture recurrence and/or re-intervention rates, which may particularly have impacted the clinical effectiveness and long-term Markov model findings. Among adults with Dupuytren's contracture, collagenase delivered in an outpatient setting is less effective but more cost-saving than limited fasciectomy. Further research is required to establish the longer-term implications of both treatments. Recurrence and re-intervention usually occur after 1 year, and therefore follow-up to 5 years or more could resolve whether the differences observed in the Dupuytren's interventions surgery versus collagenase trial to 2 years worsen. Current Controlled Trials ISRCTN18254597. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 15/102/04) and is published in full in Health Technology Assessment; Vol. 28, No. 78. See the NIHR Funding and Awards website for further award information.

Assessing long-term effectiveness and cost-effectiveness of statin therapy in the UK: a modelling study using individual participant data sets.

Cardiovascular disease has declined but remains a major disease burden across developed countries. To assess the effectiveness and cost-effectiveness of statin therapy across United Kingdom population categories. The cardiovascular disease microsimulation model, developed using Cholesterol Treatment Trialists' Collaboration data and the United Kingdom Biobank cohort, projected cardiovascular events, mortality, quality of life and healthcare costs using participant characteristics. United Kingdom primary health care. A total of 117,896 participants in 16 statin trials in the Cholesterol Treatment Trialists' Collaboration; 501,854 United Kingdom Biobank participants by previous cardiovascular disease status, sex, age (40-49, 50-59 and 60-70 years), 10-year cardiovascular disease risk [QRISK®3 (%): <5, 5-10, 10-15, 15-20 and ≥20] and low-density lipoprotein cholesterol level (< 3.4, 3.4-4.1 and ≥ 4.1 mmol/l); 20,122 United Kingdom Biobank and Whitehall II participants aged ≥ 70 years by previous cardiovascular disease status, sex and low-density lipoprotein cholesterol (<3.4, 3.4-4.1 and ≥4.1 mmol/l). Lifetime standard (35-45% low-density lipoprotein cholesterol reduction) or higher-intensity (≥45% reduction) statin. Quality-adjusted life-years and incremental cost per quality-adjusted life-year gained from the United Kingdom healthcare perspective. Cholesterol Treatment Trialists' Collaboration and United Kingdom Biobank data informed risk equations. United Kingdom primary and hospital care data informed healthcare costs (2020-1 Great British pounds); £1.10 standard or £1.68 higher-intensity generic statin therapy per 28 tablets; and Health Survey for England data informed health-related quality of life. Meta-analyses of trials and cohort studies informed the effects of statin therapies on cardiovascular events, incident diabetes, myopathy and rhabdomyolysis. Across categories of participants 40-70 years old, lifetime use of standard statin therapy resulted in undiscounted 0.20-1.09 quality-adjusted life-years gained per person, and higher-intensity statin therapy added a further 0.03-0.20 quality-adjusted life-years per person. Among participants aged ≥70 years, lifetime standard statin was estimated to increase quality-adjusted life-years by 0.24-0.70 and higher-intensity statin by a further 0.04-0.13 quality-adjusted life-years per person. Benefits were larger among participants at higher cardiovascular disease risk or with higher low-density lipoprotein cholesterol. Standard statin therapy was cost-effective across all categories of people 40-70 years old, with incremental costs per quality-adjusted life-year gained from £280 to £8530. Higher-intensity statin therapy was cost-effective at higher cardiovascular disease risk or higher low-density lipoprotein cholesterol. Both standard and higher-intensity statin therapies appeared to be cost-effective for people aged ≥70 years, with an incremental cost per quality-adjusted life-year gained of under £3500 for standard and under £11,780 for higher-intensity statin. Standard or higher-intensity statin therapy was certain to be cost effective in the base-case analysis at a threshold of £20,000 per quality-adjusted life-year. Statins remained cost-effective in sensitivity analyses. The randomised evidence for effects of statin therapy is for about 5 years of treatment. There is limited randomised evidence of the effects of statin therapy in older people without previous cardiovascular disease. Based on the current evidence of the effects of statin therapy and modelled contemporary disease risks, low-cost statin therapy is cost-effective across all categories of men and women aged ≥40 years in the United Kingdom, with higher-intensity statin therapy cost-effective at higher cardiovascular disease risk or higher low-density lipoprotein cholesterol. Cholesterol Treatment Trialists' Collaboration has ongoing studies of effects of statin therapy using individual participant data from randomised statin trials. Ongoing large randomised controlled trials are studying the effects of statin therapy in people ≥70 years old. Future economic analyses should integrate the emerging newevidence. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/140/02) and is published in full in Health Technology Assessment; Vol. 28, No. 79. See the NIHR Funding and Awards website for further award information.

Effectiveness and cost-effectiveness of online recorded recovery narratives in improving quality of life for people with psychosis experience (NEON Trial): a pragmatic randomised controlled trial

The Narrative Experiences Online (NEON) Intervention provides self-managed web-based access to mental health recovery narratives (n=659). We evaluated effectiveness and cost-effectiveness in improving quality of life for adults resident in England with mental health problems and recent psychosis experience. Prospectively registered pragmatic parallel-group randomised trial controlling for usual care, recruiting from statutory mental health services and through community engagement activities, with a 52-week primary endpoint (ISRCTN11152837). All trial procedures and the NEON Intervention were delivered by an integrated web-application. Randomisation was through an independently generated list (no stratification). Allocation was masked for statistical staff and the Chief Investigator but not participants. Intervention arm participants received immediate NEON Intervention access. Control arm participants received access after completing primary endpoint questionnaires. The primary outcome was quality of life through the Manchester Short Assessment (MANSA). Serious Adverse Events (SAEs) were collected through web-based safety report forms and identified from health service usage data. The primary analysis was by a prospectively described Intention To Treat principle excluding participants who had registered multiple times, with multiple imputation for missing data. Between 9 March 2020 and 1 March 2021, 739 participants were randomised (intervention:370; control: 369), providing more than 90% power to detect a baseline-adjusted difference of 0.25 in the MANSA score. Mean age was 34.8 years (standard deviation (SD) 12.0), 561 (75.9%) were white British, 443 (59.9%) were female, 609 (82.4%) had accessed specialist care mental health services, and 698 (94.5%) had accessed primary care mental health services. Mean baseline MANSA score was 3.7 for control and intervention arms (SD 0.9 and 1.0). 565 (76.5%) participants provided primary endpoint MANSA data with a mean score of 4.1 (SD 1.0) for both arms. We found no significant difference in Quality of Life between the two arms at the primary endpoint (baseline-adjusted difference 0.07, 95% CI-0.07 to 0.21, p=0.35). The incremental cost-effectiveness ratio (£110,501 per quality-adjusted life-year (QALY)) exceeded the prospectively defined cost-effectiveness threshold (£30,000 per QALY). 158(42.8%) control arm and 194 (52.4%) intervention arm participants accessed narratives outside of the NEON Intervention. There were no related serious adverse events (SAEs). 116 unrelated SAEs were reported by control arm participants, and 107 by intervention arm participants. Our findings do not indicate NEON Intervention access for all people with psychosis experience. Future research should consider a) evaluation with current mental health services users; b) optimisation to enable users to find hope-promoting narratives. National Institute for Health and Care Research (NIHR).

Diagnosing recipient- vs. donor-derived posttransplant myelodysplastic neoplasm via targeted single-cell mutational profiling.

Distinguishing donor- vs. recipient-derived myelodysplastic neoplasm (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is challenging and has direct therapeutical implications. Here, we took a translational approach that we used in addition to conventional diagnostic techniques to resolve the origin of MDS in a 38-year-old patient with acquired aplastic anemia and evolving MDS after first allo-HSCT. Specifically, we used single-cell transcriptional profiling to differentiate between donor- and recipient-derived bone marrow cells and established a strategy that additionally allows identification of cells carrying the MDS-associated U2AF1S34Y variant. The patient exhibited mixed donor chimerism combined with severely reduced erythropoiesis and dysplastic morphology within the granulocytic and megakaryocytic lineage along with the MDS-associated U2AF1S34Y mutation in the bone marrow. Single-cell transcriptional profiling together with targeted enrichment of the U2AF1S34Y-specific locus further revealed that, while the immune compartment was mainly populated by donor-derived cells, myelopoiesis was predominantly driven by the recipient. Additionally, concordant with recipient-derived MDS, we found that U2AF1S34Y-mutated cells were exclusively recipient derived with X but not Y chromosome-specific gene expression. Our study highlights the clinical potential of integrating high-resolution single-cell techniques to resolve complex cases for personalized treatment decisions. The study was funded by intramural resources of the Charité- Universitätsmedizin Berlin and the Berlin Institute of Health.

How the US National Institutes of Health is confronting health threats in a changing world

How the US National Institutes of Health is confronting health threats in a changing world

INTERVENÇÃO NO AUTOCUIDADO DE PACIENTES DIABÉTICOS TIPO II ATENDIDOS EM UNIDADES NO BRASIL: REVISÃO NARRATIVA DURANTE O PERÍODO 2016-2023

INTRODUCTION: Studies conducted in Brazil also corroborate the association between obesity and type 2 diabetes (DM2). More than 70% of patients diagnosed with the disease are overweight or have some degree of obesity, which reinforces the importance of sel-care as a preventive and treatment measure. OBJECTIVE: To evaluate the self-care intervention in patients with type 2 diabetes in units in Brazil. METHODOLOGY: The study is a narrative review of the literature, utilizing electronic databases such as PubMed (US National Library of Medicine National Institutes of Health), the Scientific Electronic Library Online (SciELO), and the Virtual Health Library (BVS). To analyze the descriptors most suitable for the study's objective, the Health Sciences Descriptors (DeCS) were used. RESULTS: Presentation of the articles included in the sample, highlighting the type of study, author, year, sample characteristics, and country/state, among others. DISCUSSION: Managing diabetes requires a multidisciplinary approach, involving health education, self-care, and continuous medical support. Studies have demonstrated the effectiveness of interventions focused on promoting self-care to improve health outcomes in patients with diabetes. CONCLUSION: The study highlights the importance of self-care, health education, and family support in managing type 2 diabetes mellitus. Collaboration between doctors and patients, along with the use of technologies, can enhance outcomes. Therefore, it is essential to invest in health education programs that prioritize individualization and collaboration to improve the quality of life for patients with diabetes.

Evaluating the Compliance to 24-Hour Venous Thromboembolism Risk Re-assessment Following Orthopaedic Surgery at a Tertiary Center: A Closed-Loop Clinical Audit.

Introduction Venous thromboembolism (VTE) is a preventable cause of patient morbidity and mortality among hospitalised patients. VTE events have a high incidence among orthopaedic patients, who routinely receive chemical thromboprophylaxis in the form of heparin, warfarin, antiplatelet agents or direct oral anticoagulants. These can be associated with adverse events, most commonly bleeding or heparin-induced thrombocytopenia. A VTE risk reassessment following 24 hours of admission or a change in clinical condition like surgery is recommended to avoid such complications. We evaluated the compliance to completion of these reassessments following surgery at a tertiary elective orthopaedic hospital. Methods A closed-loop audit was undertaken for all elective orthoapedic specialties. First loop was conducted between 01/07/2022 and 25/05/2023, whilst the second loop was done between 01/01/2024 and 01/02/2024. Insight, an online database was used to collect data on initial VTE assessment forms completed at admission and VTE reassessment forms completed within 24 hours of surgery, as agreed with orthopaedic teams. Audit standards were derived from National Institute for Health and Care Excellence (NICE) guidelines on venous thromboembolism in over 16s. A target compliance was agreed at 100%. Paediatric patients, day case procedures and medical admissions comprised the exclusion criteria. Results For the first audit loop, only 6/4780 (0.13%) patients had completed VTE reassessment forms within 24 hours following surgery. Following implementation of a system prompt on Electronic Patient Medication Administration (EPMA) to serve as a reminder for VTE reassessment completion, the second audit loop found 112/156 (74%) patients had completed forms (p<0.001). Conclusion VTE risk reassessment following surgery is recommended by NICE guidelines in order to assess and potentially minimize complications like bleeding and heparin-induced thrombocytopenia. A simple intervention such as a system reminder can serve to improve compliance. This can be implemented at a large scale given most hospitals use integrated electronic medication administration systems where initial VTE risk assessments are completed as part of the initial patient admission process.

Building capacity for maternal, newborn and child health research in low-income country settings: A research fellowship experience in Ethiopia.

There is a need to build research capacity to improve maternal, newborn, and child health (MNCH) in low- and middle-income countries (LMICs). To address this gap, we co-designed the HaSET (meaning 'happiness' in Amharic) MNCH Research Fellowship programme for academics and policymakers in collaboration with the Ministry of Health (MOH) and academic institutions in Ethiopia. Based on interviews and focus group discussions regarding a landscape analysis of the MNCH research environment, we developed an innovative 'learning by doing' model in which fellows identified research questions, developed proposals, obtained institutional review board (IRB) approvals, conducted research, analysed data, disseminated their findings, and developed policy briefs. Postdoctoral fellows were paired with policymakers and health professionals at the MoH to facilitate the translation of research findings into policy and programmes. Each pair received mentorship from a member of the HaSET's scientific advisory group (SAG) who had expertise in research methods, data analysis, dissemination, and translation of evidence into policy. The HaSET MNCH Research Fellowship curriculum included 10 modules covering topics from biostatistics to study operations and professional development. From March 2021 to July 2023, five postdoctoral fellows from local universities and four policymakers from the MoH and government research institutes underwent the HaSET programme, where they learned to gather high-quality evidence on priority research questions and guide the implementation of national policies and programmes. Leveraging existing data, the fellows produced 15 manuscripts and 11 policy briefs. The programme established a functional research link between the MoH, regional health bureaus, and local universities, while utilising the SAG's expertise in mentorship. This robust and comprehensive HaSET MNCH Research Fellowship produced the first cohort of dedicated fellows trained in evidence-based medicine and mentored them to become effective public health professionals. They conducted high-quality studies to inform policy decisions on MNCH interventions in Ethiopia. Given its sustainability and scalability, researchers and academic institutions can further adapt the fellowship curriculum within capacity-building programmes to educate the next generation of research leaders in LMICs.

Optimal duration of medical therapy for patients with acute myocardial infarction.

Optimal medical therapy, including Beta-blockers (BB), inhibitors of the renin-angiotensin system (RAS), and statins, is recommended for patients with acute myocardial infarction (AMI) in the absence of contraindications. However, the optimal duration of these medications has not been clearly established in clinical studies. This observational study aimed to investigate the period during which these medications are associated with improved clinical outcomes. Among patients enrolled in the Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH), in-hospital survivors were selected. In a Cox-proportional hazard analysis of 12,200 patients, BB (hazard ratio [HR] = 0.73; 95% confidence interval [CI] = 0.57-0.95; P = .019), RAS inhibitors (HR 0.70; 95% CI = 0.55-0.89; P = .004), and statins at discharge (HR = 0.65; 95% CI = 0.48-0.87; P = .004) were all associated with lower 1-year cardiac mortality. At 1-year, 10,613 patients without all-cause death, myocardial infarction, revascularization, or re-hospitalization due to heart failure were selected for further analysis. RAS inhibitors (HR = 0.53; 95% CI = 0.37-0.76; P = .001) and statins (HR = 0.30; 95% CI = 0.14-0.61; P = .001) prescribed at 1-year were associated with lower 2-year cardiac mortality, whereas BB were not (HR = 0.79; 95% CI = 0.51-1.23; P = .23). However, none of these medications prescribed at 2-years were associated with reduced 3-year cardiac mortality among the 9232 patients who remained event-free until then. RAS inhibitors and statins were associated with reduced cardiac mortality for up to 2-years, and BB for up to 1-year after the initial attack. The effectiveness of these medications beyond these periods remains questionable.

A qualitative study of adaptation challenges of Ukrainian refugees in the United States

This study examines adaptation challenges faced by Ukrainian refugees living in the United States (U.S.), with a focus on families with children. Since 2022, an estimated 6.8 million Ukrainian refugees have left the country, including at least 221,000 to the U.S. This population has experienced trauma and displacement and now faces new challenges of adaptation and acculturation in the U.S. after resettlement. The research team conducted in-depth interviews with 32 Ukrainian refugees and generated themes from the responses using qualitative grounded theory research methods. Findings indicated Ukrainian refugees in the U.S. are struggling with multiple adaptation challenges which group into five themes: 1) coping with the stressors of displacement, family separation, and pre-migration trauma, 2) maintaining mental health and well-being while adapting, 3) navigating the language barrier, 4) coping with gender-role conflicts related to employment status, and 5) acculturating to everyday life with U.S. institutions of education, health, transportation, and social assistance. Implications for practitioners and policymakers include clarifying future visa status for Ukrainian refugees, making English language classes and automatic translation technology easily accessible, supporting intra-community and remote mental health services, and developing economic and social packages to help this population adapt and acculturate resiliently into U.S. society. The findings are also informative for the comparative understanding of adaptation pathways of different groups of refugees and are relevant for perspectives on life course development under conditions of acculturation, trauma, and displacement.

Developing a Multiscale Neural Connectivity Knowledgebase of the Autonomic Nervous System.

The Stimulating Peripheral Activity to Relieve Conditions (SPARC) program is a U.S. National Institutes of Health (NIH) funded effort to enhance our understanding of the neural circuitry responsible for visceral control. SPARC's mission is to identify, extract, and compile our overall existing knowledge and understanding of the autonomic nervous system (ANS) connectivity between the central nervous system and end organs. A major goal of SPARC is to use this knowledge to promote the development of the next generation of neuromodulation devices and bioelectronic medicine for nervous system diseases. As part of the SPARC program, we have been developing SCKAN, a dynamic knowledge base of ANS connectivity that contains information about the origins, terminations, and routing of ANS projections. The distillation of SPARC's connectivity knowledge into this knowledge base involves a rigorous curation process to capture connectivity information provided by experts, published literature, textbooks, and SPARC scientific data. SCKAN is used to automatically generate anatomical and functional connectivity maps on the SPARC portal. In this article, we present the design and functionality of SCKAN, including the detailed knowledge engineering process developed to populate the resource with high quality and accurate data. We discuss the process from both the perspective of SCKAN's ontological representation as well as its practical applications in developing information systems. We share our techniques, strategies, tools and insights for developing a practical knowledgebase of ANS connectivity that supports continual enhancement.

Forgotten older people: health system debt.

The exercise of all human rights is inherent to all persons, which must be guaranteed by the States regardless of the characteristics of all persons, such as age, gender, sexual preferences, ethnic origin, nationality or migratory status. This document presents a reflection on the discrimination that older people face not only because they are older (ageism), but also because of other characteristics that place them in a situation of greater vulnerability and discrimination, such as belonging to the LGBT+ community, being in prisons or having HIV. It urges reflection on the role and sensitivity with which public institutions, mainly health institutions, must have to guarantee a fundamental right such as health, not only in the physical aspect but also in the mental one. The health challenges that the country faces are presented, and a call is made to leave no one behind, encouraging the most vulnerable populations to have immediate attention free of discrimination. The elderly are the present and the future of the realities of our countries, where Mexico is no exception.

Mentoring Early-Career Investigators of HIV/STI Health Disparities Research: A Study Examining the CAPS Visiting Professors Program.

To build research capacity for early-career faculty conducting HIV/STI research with minoritized communities and to enhance diversity in the scientific workforce, the University of California, San Francisco (UCSF) Center for AIDS Prevention (CAPS) conducts a training program for visiting professors (VPs), begun in 1996. VPs are in residence at CAPS for three summers, complete a pilot research project, and prepare National Institutes of Health (NIH) grant proposals. Best practices and key elements for successfully training scholars of color, and others who work with minoritized communities, are identified. This paper draws on qualitative interviews with 31 VPs and 10 program mentors (VPMs) who participated in the program between 1996 and 2016. All VPs were also invited to participate in an anonymous survey to assess potential differences between study participants and non-participants. Interviews took place between September 2017 and March 2018 and were audio-recorded, transcribed, and thematically coded. VPs and VPMs described key elements relevant to both human and social capital that contributed to Program success. Paramount among these were the importance of establishing trusting mentorship relationships; sustained collegial engagement over time; and fostering a training environment based on multidisciplinarity, skills-building, scholarly networking, and peer reviews. Participant voices from this objectively successful training program provide directions for future initiatives to support scholars of color and those working with minoritized groups. An indispensable value of such programs is to intentionally foster trusted scholarly communities to counterbalance systemic inequities in the academy.

Inequalities in geographic barriers and patient representation in lymphoma clinical trials across England.

The distribution of trial site locations may lead to disparities in geographic access and affect patient representativeness in clinical trials. We utilised trial data covering 1993-2022 from the National Institute for Health and Care Research (NIHR) Open Data Platform, 2011 and 2021 English Census and geographic data and English individual-patient cancer registry data for patients diagnosed with lymphoma between 1997 and 2017. To assess representation, we compared patient age and sex between trial participants and the incident population. We mapped the distance and travel times of English lower layer super output areas (LSOAs) to their nearest research active NHS Trusts and assessed associations between distance and travel times and the geographic and sociodemographic characteristics of the LSOAs. Trial participants were younger than the incident population and more likely to be male. The closest NHS Trust to more than half of English LSOAs was not research active. Greater LSOA mean age, male percent, White British percent, rurality and coastal/border status were positively associated with distance and travel time (at prespecified p < 0.05 level), while greater deprivation was negatively associated. Female and older lymphoma patients in England are underrepresented in trials, with the latter facing a higher burden of geographic barriers.

Signatures of transmission in within-host Mycobacterium tuberculosis complex variation: a retrospective genomic epidemiology study

Mycobacterium tuberculosis complex (MTBC) species evolve slowly, so isolates from individuals linked in transmission often have identical or nearly identical genomes, making it difficult to reconstruct transmission chains. Finding additional sources of shared MTBC variation could help overcome this problem. Previous studies have reported MTBC diversity within infected individuals; however, whether within-host variation improves transmission inferences remains unclear. Here, we aimed to quantify within-host MTBC variation and assess whether such information improves transmission inferences. We conducted a retrospective genomic epidemiology study in which we reanalysed publicly available sequence data from household transmission studies published in PubMed from database inception until Jan 31, 2024, for which both genomic and epidemiological contact data were available, using household membership as a proxy for transmission linkage. Wequantified minority variants (ie, positions with two or more alleles each supported by at least five-fold coverage and with a minor allele frequency of 1% or more) outside of PE and PPE genes, within individual samples and shared across samples. We used receiver operator characteristic (ROC) curves to compare the performance of a general linear model for household membership that included shared minority variants and one that included only fixed genetic differences. We identified three MTBC household transmission studies with publicly available whole-genome sequencing data and epidemiological linkages: a household transmission study in Vitória, Brazil (Colangeli etal), a retrospective population-based study of paediatric tuberculosis in British Columbia, Canada (Guthrie etal), and a retrospective population-based study in Oxfordshire, England (Walker etal). We found moderate levels of minority variation present in MTBC sequence data from cultured isolates that varied significantly across studies: mean 168·6minority variants (95% CI 151·4-185·9) for the Colangeli etal dataset, 5·8 (1·5-10·2) for Guthrie etal (p<0·0001, Wilcoxon rank sum test, vsColangeli etal), and 7·1 (2·4-11·9) for Walker etal (p<0·0001, Wilcoxon rank sum test, vs Colangeli etal). Isolates from household pairs shared more minority variants than did randomly selected pairs of isolates: mean 97·7shared minority variants (79·1-116·3) versus 9·8 (8·6-11·0) in Colangeli etal, 0·8 (0·1-1·5) versus 0·2(0·1-0·2) in Guthrie etal, and 0·7 (0·1-1·3) versus 0·2 (0·2-0·2) in Walker etal (allp<0·0001, Wilcoxon rank sumtest). Shared within-host variation was significantly associated with household membership (odds ratio 1·51 [95% CI 1·30-1·71], p<0·0001), for one standard deviation increase in shared minority variants. Models that included shared within-host variation versus models without within-host variation improved the accuracy of predicting household membership in all three studies: area under the ROC curve 0·95versus 0·92for the Colangeli etal study, 0·99versus 0·95for the Guthrie etal study, and 0·93versus 0·91for the Walker etal study. Within-host MTBC variation persists through culture of sputum and could enhance the resolution of transmission inferences. The substantial differences in minority variation recovered across studies highlight the need to optimise approaches to recover and incorporate within-host variation into automated phylogenetic and transmission inference. National Institutes of Health.