Association between changes in adherence to the planetary health diet and adiposity and body fat distribution: a cohort study

Dengue epidemiology and transmission intensity across Panama during 2000-2024: a modelling study.

Comorbid diabetes disease severity and microbial changes in patients with bronchiectasis: a combined analysis of data from the EMBARC, EMBARC-India, Australian, and BE-China registries.

BackgroundType 2 diabetes is a growing challenge in low- and middle-income countries (LMIC), where health systems face major capacity gaps. Participatory learning and action (PLA) has shown effectiveness in preventing type 2 diabetes in Bangladesh, but little is known about its use in other LMICs for diabetes. The EMPOWER-D (Engagement of community through Participatory learning and action for cOntrol and prevention of type 2 diabetes) trial is testing PLA for diabetes prevention in communities in Pakistan and Afghanistan. This protocol describes the plans for the embedded process evaluation (PE).MethodsThe PE will use a mixed-methods design across three sites, following the UK Medical Research Council framework for PE, examining implementation, mechanisms of impact and context. Implementation will be assessed using adaptation reports, fidelity checklists, attendance data and supervisor reports. Mechanisms of impact will be explored through interviews, focus group discussions and photovoice. Contextual factors will be examined through interviews with participants, community mobilisers, supervisors and key stakeholders. Quantitative data will be analysed descriptively, while qualitative data will undergo thematic analysis using a theory of change framework. Comparative analysis will identify common and context-specific influences.DiscussionThis is the first multi-country PE of a PLA intervention for diabetes prevention to our knowledge, and the first in Afghanistan and Pakistan. The study will provide insights into how the intervention was delivered, how and why it worked (or did not work) and the contextual factors shaping outcomes. Findings will inform the adaptation and scale-up of participatory approaches for non-communicable disease prevention in resource strained setting health systems. Trial registration: ClinicalTrials.gov: NCT06561126 (registered 23 August 2024); NCT06570057 (registered 26 August 2024).

Infective endocarditis is an infectious heart disease strongly associated with morbidity and mortality. Up to half of the patients with infective endocarditis require heart valve surgery. While early exercise-based rehabilitation is well documented for patients recovering from heart surgery for non-infective endocarditis, there is limited research on those who have undergone valve surgery due to this infection. This study aimed to explore the early aerobic training in this patient population. A single-centre prospective feasibility study was conducted using the UK Medical Research Council's framework for complex interventions. The study investigated the feasibility (recruitment, retention, adherence), safety, acceptability, and preliminary functional outcomes of 4 × 4 interval training in this patient population. Training session data included the number, duration, and intensity, which were monitored via the Apple Watch S5 (Present Age-Predicted Maximum Heart Rate) and the Borg RPE scale. Functional outcomes were evaluated at baseline and 3 months post-surgery, including sub-maximal oxygen uptake (treadmill protocol), 6-min walk test, and quality of life (HeartQoL, EQ-5D-5L). Sixteen patients consented to participate, with 12 initiating the intervention and 11 completing it, yielding a retention rate of 91.7%. Training adherence averaged 73.1% of the minimum expected sessions, with high participant satisfaction and no serious adverse events reported. At the 12-week follow-up, participants demonstrated measurable change in functional capacity, including an increase in workload capacity (+ 95 W), METs (+ 3.4), and 6-min walk test distance (+ 219m). Health-related quality of life also showed a noticeable increase, with HeartQoL physical and emotional scores increasing by 1.0 and 1.3, respectively, and EQ-5D-5L VAS scores rising by 17.2. The EQ-5D-5L index increased from 0.61 at baseline to 0.87 after 12weeks. Interval training, when conducted with appropriate safeguards and tailored to individual needs, is a feasible and safe intervention for patients recovering from endocarditis and cardiac surgery. The observed improvements in functional capacity, quality of life, and patient satisfaction support the need for larger controlled studies. Clinical Trials, ID NCT05703022. Registered on 25 November 2021, http://www. gov.

Rehabilitation after stroke is a complex process, and innovative solutions, including digital tools, have been suggested as way of meeting the challenge of limited access to services. F@ce 2.0 is a person-centred intervention for rehabilitation after stroke where goal achievement is supported by information and communication technology. Guidance for evaluation of complex interventions, such as that from the UK Medical Research Council (MRC), underlines the importance of evaluating not only the effects of an intervention but also process, such as its implementation in a clinical setting. The objective was therefore to study the implementation process of the F@ce 2.0 intervention for stroke survivors living at home as well as the interaction between the intervention and the implementation context. A process evaluation of the implementation of F@ce 2.0 was conducted, informed by the MRC guidance for process evaluations, utilising a convergent mixed methods design. Participants included stroke survivors (n = 39), rehabilitation team members (n = 53) and managers (n = 6). Data were collected through a web server, surveys and interviews. Descriptive statistics were used for quantitative analysis. Qualitative data were analysed using a deductive thematic approach based on the Consolidated Framework for Implementation Research. Analysis revealed challenges in conducting research during the COVID-19 pandemic as well as limitations related to implementation planning in relation to the specific context. The reach of the intervention among stroke survivors was low, and fidelity issues were identified related to the teams' lack of readiness to deliver the intervention. Analysis of teams' perception of delivering the intervention revealed that they saw potential in using a structured instrument for person-centred goal setting and in goal reminders, but also a hesitation regarding the usability of the intervention for stroke survivors. Teams also expressed a need of further education in delivering the intervention. The process evaluation showed that although rehabilitation teams recognized the potential of F@ce 2.0, implementation and reach were limited, largely due to insufficient contact with the teams for both support and monitoring. Earlier involvement of the rehabilitation teams would likely have helped identify educational needs and organizational conditions necessary for successful implementation. ClinicalTrials.gov NCT04351178. Firs posted 2020-04-17. https://clinicaltrials.gov/study/NCT04351178 .

An estimated 150 million people have mental health care needs in India, but only 15% are able to access care. Depression and anxiety contribute to a large proportion of mental morbidity. The Systematic Medical Appraisal, Referral, and Treatment (SMART) Mental Health trial used a mobile-based clinical decision support system for primary care doctors and community health workers (CHWs) to identify and treat people at risk of depression, anxiety disorders, and self-harm. A community-based antistigma campaign was also delivered. The intervention led to improved remission rates for depression and anxiety and lower stigma scores. A process evaluation assessed (1) implementation fidelity, barriers, and facilitators; (2) perceptions of doctors and CHWs on the use of SMART Mental Health; and (3) the causal pathways that led to trial outcomes. A mixed methods evaluation combining backend program data and qualitative data was conducted. A total of 38 focus group discussions and 37 key informant interviews were conducted with primary doctors, CHWs, government officials, local community leaders, and research project staff. The data were coded and analyzed using a framework analysis approach based on the UK Medical Research Council guidance on process evaluations and the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. The intervention had high implementation fidelity. Across clusters, the median proportion of participants with at least 1 CHW follow-up was 98% (IQR 96.6%-100%). The referral rate for a psychiatrist was low (224/1697, 13.2%), and only 23.6% (53/224) of those referred visited the psychiatrist. The median exposure to antistigma audiovisual content was 84% (IQR 65.7%-95.9%). At the community level, key implementation barriers included cultural inhibitions in seeking mental health care and the unavailability of patients due to competing demands. Proximity and tight social connections between CHWs and their communities were important facilitators in seeking medical help. Doctor and CHW training, mentoring, and feedback provided by program staff were important facilitators to support the use of the digital health components by the health workforce. A complex intervention that included both community-based antistigma and clinical digital health interventions achieved high implementation fidelity. Key areas to consider for maintenance of such interventions include (1) the need for sustained community-based strategies to address stigma and other cultural barriers; (2) health workforce strengthening policies, including supportive supervision for CHWs and doctors to increase capability in the use of mental health digital health tools; and (3) strategies to improve access to specialist care for those with more complex care needs. Clinical Trial Registry India CTRI/2018/08/015355; https://tinyurl.com/5r63suxp.

The UK Medical Research Council's Guidance on Developing and Evaluating Complex Interventions (MRC GDECI) outlines a 4-phase framework for structuring research programs on interventions: development, feasibility, evaluation, and implementation. However, it provides limited practical direction on how researchers should select which phases to conduct or determine when and whether to progress between phases. This gap is particularly challenging in the context of digital health interventions (DHIs), given their fast-paced and rapidly evolving nature. This scoping review examined the research phases conducted, how researchers progressed through them, and the intervention characteristics associated with overall program structure and duration in DHI research, to inform the design of future research programs. We searched PubMed, Embase, CINAHL, PsycINFO, and ClinicalTrials.gov to identify complex DHIs promoting health among adolescents and young adults, implemented between 2017 and 2026, for which at least 2 phases of the MRC GDECI were reported, including the evaluation phase. For each eligible intervention, all related protocols, preprints, and published articles were retrieved to reconstruct the full research program. For each program, we analyzed the presence of each research phase, its organization (ie, phase arrangements), and the mechanisms guiding progression between phases (ie, progression mechanisms). Phase-specific and overall program durations were recorded. A total of 31 research programs, covering 31 interventions and reported in 130 articles, were included. Development, feasibility, evaluation, and implementation phases were reported in 26, 23, 31, and 7 research programs, respectively. Three types of phase arrangements were identified: sequential, iterative, and overlapping. Progression mechanisms between phases included automatic progression, conditional progression based on researchers' appraisal of findings without prespecified criteria, and progression based on predefined quantitative criteria. Six main research program structures were observed, combining phase arrangements and progression mechanisms. Iterative arrangements were most common, observed in 22 research programs, followed by overlapping (n=10) and strictly sequential structures (n=7). Most progressions relied on researchers' appraisal of findings without prespecified criteria. Justifications for phase iteration, omission, or progression decisions were rarely reported. The median program duration was 5.8 (IQR 3.8-6.6) years (n=13). Based on these findings, a novel 4-step operational framework and visualization tools were developed to guide the design and planning of DHIs, highlighting key considerations for each step, as well as the strengths, limitations, and risks associated with each phase arrangement and progression mechanism. This scoping review is the first to systematically examine phase arrangements and progression mechanisms in DHI research programs. Beyond descriptive reporting, it provides a conceptualization of research program structures and offers a flexible operational framework to support the concrete implementation of the MRC GDECI. Greater explicitness in decisions about program structure may enhance methodological rigor, reduce research waste, and improve the integrity and reproducibility of interventions. PROSPERO CRD42023401979; https://tinyurl.com/mvc265y3.

Chronic stroke and spinal cord injury (SCI) lead to persistent motor impairments that reduce independence and quality of life. Although rehabilitation is essential to address these challenges, the amount of therapy provided during the chronic phase remains limited, while the long-term costs of care are substantial. The INTeRAcT (Intensive Rehabilitation Programme Integrating Advanced Technology) trial investigates a high-dose, intensive-targeted, and personalized rehabilitation program through an integrated clinical, health economic, and process evaluation. This single-blind randomized controlled trial will include 100 adults in the chronic phase after stroke or SCI. Participants will be randomized to either the INTeRAcT intervention group (n=50) or a control group receiving usual care (n=50). The intervention group will receive 90 hours of personalized motor rehabilitation over 3 weeks, including upper and lower limb therapy, with and without technology, cardiovascular fitness training, and self-management education. Both groups then resume usual care and are followed for 9 months. Clinical assessments are performed at baseline (T0), after 3 weeks (T1, postintervention), and after 9-months follow-up (T2) by a blinded assessor. The primary outcome is independence in daily life, assessed using the Functional Independence Measure for stroke and the Spinal Cord Independence Measure for SCI. Secondary outcomes include the EQ-5D-5L, Canadian Occupational Performance Measure, Goal Attainment Scaling, Fatigue Severity Scale, and stroke-specific measures such as the Action Research Arm Test, Fugl-Meyer Assessment, 6-Minute and 10-Meter Walk-Test, and the Stroke Self-Efficacy Questionnaire. Group differences in clinical change will be analyzed using multivariate linear models. Health economic data will be collected using diaries and questionnaires, capturing direct and indirect costs. Cost-effectiveness will be assessed through a trial-based cost-utility analysis over 9 months and a Markov model over a lifetime horizon. The process evaluation follows the UK Medical Research Council framework, using mixed methods with quantitative and qualitative data from diaries, interviews, and observations, analyzed descriptively and thematically. The funding of the project started in February 2023. Protocol version 5 (accepted March 15, 2024). Participant recruitment occurred between June 2023 and September 2024, with a total of 102 participants enrolled. Data collection ended in July 2025. Data analysis is ongoing. This protocol outlines a randomized controlled trial integrating clinical, health economic, and process evaluations to assess a high-dose, individualized rehabilitation program. The findings will provide evidence on effectiveness, cost-effectiveness, and implementation feasibility in chronic stroke and SCI, supporting the optimization of long-term neurorehabilitation care.

Effects of ovarian ablation or suppression on breast cancer recurrence and survival: patient-level meta-analysis of 15 000 women in 23 randomised trials.

Translating brain anatomy and disease from mouse to human in latent gene expression space.

International guidelines for treatment of children with severe acute malnutrition advise against giving standard oral rehydration solutions (ORS) for dehydration secondary to diarrhoea. Instead, they recommend exclusive use of low-sodium rehydration solution for malnutrition (ReSoMal), due to concerns about both sodium and fluid overload. Supportive evidence is lacking, warranting reappraisal of this guidance. We aimed to assess the safety and superiority of standard WHO-ORS versus ReSoMal. GASTROSAM was a phase 2, factorial, open-label, superiority randomised controlled trial conducted at six hospitals in four African countries (Kenya, Niger, Nigeria, and Uganda). Children aged 6 months to 12 years with severe acute malnutrition who were admitted to hospital with severe (stratum A) or moderate (stratum B) dehydration and diarrhoea were randomly assigned in a 1:1 ratio to receive ReSoMal or low-osmolarity WHO-ORS. A simultaneous randomisation in stratum A compared two intravenous strategies versus an oral control rehydration strategy (results reported elsewhere). Children with severe dehydration (stratum A) received their allocated ORS as soon as possible. The primary endpoint was change in sodium concentration at 24 h from baseline in all randomised participants and analysed on an intention-to-treat basis. Children with lived experience were not involved in the study design. The trial is registered on the ISRCTN registry (ISRCTN76149273) and the Pan-African Clinical Trials Registry (PACTR202103852542919). Between Sept 2, 2019, and Oct 27, 2024, 415 eligible children were enrolled (218 [53%] male; 197 [47%] female); 272 were enrolled into stratum A (137 to ReSoMal and 135 to WHO-ORS) and 143 were enrolled into stratum B (69 to ReSoMal and 74 to WHO-ORS). Children were followed up for 28 days; 11 (3%) were lost to follow-up or withdrew. The primary endpoint was assessed in 387 (93%) of 415 participants. The increase in sodium concentration was similar in both groups (5·3 mmol/L [SD 8·1] with ReSoMal vs 5·0 mmol/L [7·6] with WHO-ORS; mean difference for WHO-ORS vs ReSoMal -0·6 [95% CI -1·9 to 0·7], p=0·37). There was no difference in day 28 mortality between the WHO-ORS and ReSoMal groups (19 [9%] vs 24 [12%]; adjusted hazard ratio 0·76 [95% CI 0·41 to 1·41], p=0·39). Fluid overload events (pulmonary oedema and cardiac overload) were actively monitored: none was observed. WHO-ORS resulted in similar outcomes to ReSoMal, and neither strategy led to fluid overload. This finding informs the simplification of guidelines supporting the use of WHO-ORS for the management of dehydration in children regardless of nutritional status. Joint Global Health Trials Scheme of the UK Medical Research Council, UK Department for International Development, Wellcome, and Médecins Sans Frontières.

Protecting children aged 1-5 years from drowning in low-income deltaic or riverine regions like the Sundarbans, India, has proven to be challenging due to resource and access constraints. Fencing of water bodies to prevent access is one low-cost intervention proposed for resource-limited settings. We co-developed, implemented a prototype and conducted a process evaluation of a fencing intervention for the first time in a low-income region and assessed its acceptability and feasibility. The study was conducted in the rural region of Sundarbans, India, which faces some of the highest child drowning rates globally. 100 households with children received the intervention where nearby ponds were fenced and monitored over 1 year. The process evaluation was guided by UK Medical Research Council's Guidance for Evaluating Complex Interventions. Quantitative data assessing the fence's safety and use were collected at baseline and four quarterly monitoring visits. Qualitative data was collected from participants, non-participants, self-motivated fence-builders and project team members to understand barriers and enablers to usage and maintenance. Results showed high levels of acceptability by community members, who showed ownership to build and maintain the fencing. However, long-term sustainability may be impacted for those unable to afford materials for maintenance. Community engagement was essential in ensuring continuous use, particularly the involvement of community leaders. Buy-in could be improved by holding engagement sessions in the evening when household decision-makers were available. The fencing intervention was found to be successful and may be considered for larger scale-up to assess its effectiveness against drowning.

Efficacy and safety of short-cycle, dolutegravir-based antiretroviral therapy in adolescents living with HIV (BREATHER Plus): a multicentre, open-label, randomised, parallel, two-arm, non-inferiority trial.

The FirstCPR cluster randomised trial delivered multimodal basic life support (BLS) learning opportunities to community organisations. An a priori process evaluation examined intervention implementation, including participation, reach, uptake and member engagement. The study used a multimethod process evaluation. Data were collected via semistructured interviews, focus group discussions, participant surveys, study records, web analytics and in-field observations. These sources captured participation patterns and implementation measures (delivery, reach, uptake and engagement: opt-in to digital messages and attendance at training sessions), as well as reasons for refusals and withdrawals. Qualitative data were analysed thematically and organised using the UK Medical Research Council process-evaluation framework. Qualitative and quantitative data were analysed separately and subsequently interpreted collectively to contextualise implementation patterns and identify barriers and enablers that influenced trial successes and failures. Intervention uptake and engagement varied significantly across organisations, with greater success observed in social and faith-based groups. Of the 82 intervention clusters, 78 (95%) received intervention materials; 74 (90%) engaged in at least one activity and 15 (18%) engaged in all activities. Participation was primarily driven by the organisation's leadership interest and support in providing BLS training to members, and by the time available to facilitate intervention activities. The presence of a dedicated liaison/champion emerged as the most critical enabler of member engagement and implementation. Feedback recommended concise, simple and culturally tailored modules, with practical components delivered in shorter, convenient sessions. Intervention delivery was affected by contextual challenges, including COVID-19 disruptions that limited in-field recruitment and group activities. Process evaluation can strengthen community-based interventions by identifying mechanisms and contextual factors that shape implementation and engagement. Partnering with social and faith-based organisations may be an effective approach to disseminating educational programmes such as life-saving skills to lay communities. Minimising research burden and ensuring organisational leadership support may improve participation while brief, practical and culturally tailored training may enhance engagement. ACTRN12621000367842.

A new community centre in a district with a high amount of equity deserving populations in Halle (Saale), Germany provides a space to design and implement health-related services that reflect the needs and priorities of local residents. Health information often fails to meet existing quality standards. Therefore, strengthening critical health literacy is essential. Co-creation is a participatory approach that addresses needs by involving community members as equal partners in the joint development of ideas, concepts and interventions. The study aims to co-create interventions with residents of the community to promote critical health literacy. The study will be conducted as an iterative co-creation process and feasibility study using both qualitative and quantitative methods, based on the PRODUCES+ framework and guided by the UK Medical Research Council (MRC) framework for developing and evaluating complex interventions. In phase I, co-creators engage in a multi-step co-creation process involving participatory workshops and focus group interviews to explore community health needs, information behaviours and to co-develop tailored interventions. Interest-holders representing local institutions are continuously involved to ensure contextual relevance and sustainability. The co-creation process will be evaluated using the PROSECO framework. In phase II, the developed interventions will undergo feasibility testing and pilot implementation within the newly established community centre, using qualitative and quantitative methods such as think-aloud, observations, interviews and questionnaires. The study is expected to develop interventions that will strengthen critical health literacy and empower residents to make informed health decisions. It will also provide insights into mechanisms and success factors of co-creation.

Type 2 diabetes is the leading cause of kidney failure and is predominantly managed in primary care. Large randomised trials have shown that GLP-1 receptor agonists and SGLT2 inhibitors each slow kidney disease progression, but their combined effect on kidney outcomes remains unclear. We aimed to evaluate the comparative effectiveness of GLP-1 receptor agonists versus DPP-4 inhibitors or sulfonylureas on kidney outcomes in individuals with type 2 diabetes already receiving SGLT2 inhibitor treatment. In this observational study, we emulated a pragmatic target trial using an active-comparator, new-user cohort design with UK primary care electronic health record data (Clinical Practice Research Datalink, March 31, 2013-March 31, 2023) with linkage to hospital inpatient, deprivation, and mortality data. We included individuals with type 2 diabetes already receiving SGLT2 inhibitors who newly initiated either GLP-1 receptor agonists or comparator drugs DPP-4 inhibitors or sulfonylureas. We excluded those with estimated glomerular filtration rate (eGFR) of less than 20 mL/min per 1·73 m2 or end-stage kidney disease. Individuals in the comparator group who initiated a GLP-1 receptor agonist during follow-up were censored at the date of GLP-1 receptor agonist initiation and subsequently re-entered into the GLP-1 receptor agonist group. We followed up all initiations regardless of subsequent treatment discontinuation (intention-to-treat analysis), with a maximum follow-up of 3 years. The primary outcome was kidney disease progression (defined as occurrence of ≥40% eGFR decline, end-stage kidney disease, or death from kidney-related causes). Safety outcomes were acute pancreatitis and incident retinopathy (among those without a recorded history at baseline). We estimated hazard ratios (HRs) using Cox proportional hazards models with double-robust overlap weighting. We included 33 659 treatment initiations (20 039 GLP-1 receptor agonists and 13 620 DPP-4 inhibitors or sulfonylureas; among 31 650 unique individuals), of whom these initiations occurred among 20 239 (60%) male individuals and 13 420 (40%) female individuals; median age was 60 years (IQR 53-67), and 26 530 (79%) were White, 4492 (13%) south Asian, 1398 (4%) Black, and 1239 (4%) of other ethnicities. Over a median follow-up of 1·4 years (IQR 0·6-3·0), kidney disease progression occurred in 187 (0·9%) of 20 039 individuals who initiated a GLP-1 receptor agonist and 189 (1·4%) of 13 620 who initiated a DPP-4 inhibitor or sulfonylurea. GLP-1 receptor agonist initiation was associated with a lower risk of kidney disease progression compared with DPP-4 inhibitor or sulfonylurea initiation (HR 0·73 [95% CI 0·58-0·92]). GLP-1 receptor agonist initiation was not associated with occurrence of acute pancreatitis (32 [0·2%] of 19 727 individuals with no recorded history of pancreatitis who initiated a GLP-1 receptor agonist vs 25 [0·2%] of 13 305 who initiated a DPP-4 inhibitor or sulfonylurea; HR 0·94 [0·52-1·70]) or incident diabetic retinopathy (1097 [10·1%] of 10 844 individuals with no recorded history of diabetic retinopathy who initiated a GLP-1 receptor agonist vs 936 [10·7%] of 8719 who initiated a DPP-4 inhibitor or sulfonylurea; HR 1·07 [0·97-1·18]). These real-world data suggest that the kidney-protective benefits of GLP-1 receptor agonists observed in randomised trials of individuals with type 2 diabetes might also extend to individuals already receiving SGLT2 inhibitors. This finding supports consideration of combination treatment for kidney protection in primary care, particularly in individuals at highest absolute risk. Further prospective data would be valuable to confirm these findings. UK Medical Research Council.

Some common infections are associated with poorer age-related health outcomes; however, findings are limited to a small number of pathogens and frequently inconclusive. This study aimed to expand the range of pathogens investigated in relation to frailty and mortality in older age. We investigated relationships between seropositivity for 18 viruses, bacteria and protozoa with concurrent frailty and prospective mortality in middle-aged and older adults within two UK population-based cohorts: UK Biobank (N = 9427; aged 40-70 years) and Medical Research Council National Survey of Health and Development (N = 1791; aged 60-65 years). Multiplex serological assays were used to identify seropositivity for each pathogen and frailty was assessed using a frailty index measuring the accumulation of age-related health deficits. Mortality was determined from linked administrative records. Adjusting for sex, age, income and education, previous infection with Toxoplasma gondii ((β = 0.77%; 95% CI, 0.42-1.11) and Helicobacter pylori (0.63%; 95% CI, 0.28-0.97) were associated with higher frailty equivalent to 3.8 or 3.1 years of aging, as was inflammation-weighted pathogen burden (0.41%/SD, 95% CI, 0.25-0.57; 0.42%/SD, 95% CI, 0.26-0.58). Previous infection with Chlamydia trachomatis, human herpes simplex virus 1 and cytomegalovirus were associated with increased frailty after adjustment for sex and age, although relationships were confounded by socioeconomic circumstances. No common infections were robustly associated with mortality. Our results indicate that infection with H. pylori and T. gondii, and the combined burden of infection may detrimentally impact ageing health. These pathogens may warrant targeting beyond current clinical measures to mitigate the development of frailty.

Despite known maternal, perinatal, and infant health risks of tuberculosis during pregnancy, global estimates of incidence remain scarce. Existing estimates are outdated, and do not include the postpartum period, HIV co-infection, age, or specific changes in risk, limiting our understanding of the true scale of disease in this understudied population. In this rapid review and modelling analysis, we estimated the global tuberculosis incidence in pregnant and postpartum women using a population-based modelling approach. We searched MEDLINE and EMBASE, with no date or language limits, and included studies reporting tuberculosis incidence in pregnancy or postpartum with suitable comparison groups; we also used Feb 6, 2025, interim data from the ongoing ORCHID cohort. We combined WHO age and sex-stratified tuberculosis incidence data with country-specific population and fertility data to estimate baseline tuberculosis incidence, and applied systematic review-based risk ratios to account for elevated increased risk during pregnancy and postpartum. Uncertainty in all inputs was propagated using standard error propagation formulae and summarised as mean tuberculosis incidence rates and mean incidence rate ratios (IRRs), each reported with 95% quantile-based uncertainty intervals (UIs). We identified 37 studies published between 1996 and 2020, of which three were of sufficient quality to provide data for HIV-negative women. One additional study (ORCHID; Odayar et al, unpublished) provided data for women living with HIV. Compared with non-pregnant women without HIV, tuberculosis IRRs were 1·34 (95% CI 1·17-1·54) during pregnancy and 1·91 (1·53-2·39) during postpartum among HIV-negative women. For women living with HIV, IRRs were 5·73 (95% CI 2·64-10·94) during pregnancy and 3·58 (0·85-9·63) postpartum. We estimated 239 500 pregnant women (95% UI 216 300-262 800) and 97 600 postpartum women (90 100-105 200) developed tuberculosis disease globally in 2023, with HIV contributing to 21·3% (19·8-22·8) and 10·6% (9·9-11·3) of cases, respectively. The WHO African region had the highest incidence (110 600 [95% UI 96 700-124 500] in pregnant women and 40 900 [36 300-45 400] in postpartum women), followed by the South-East Asia region (79 900 [64 100-95 700] in pregnant women and 35 900 [30 800-41 100] in postpartum women). Pregnant and postpartum women face substantial tuberculosis risk, yet remain under-represented in global estimates. Our findings underscore the need for improved surveillance and targeted interventions to reduce tuberculosis incidence in this group. UK Medical Research Council.

The role of frailty and comorbidities in severe infections and the risk of dementia: a prospective, multicohort, observational study.