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Cardiovascular diseases (CVDs) represent a growing public-health challenge in India, where nearly one in four deaths is CVD-related. Accurate risk stratification underpins targeted prevention, yet laboratory-dependent tools are often impractical in resource-limited settings. The World Health Organization (WHO) and GLOBORISK initiatives both offer non-laboratory-based 10-year CVD risk algorithms alongside their laboratory-based counterparts. We aimed to compare laboratory- and non-laboratory-based WHO and GLOBORISK CVD risk scores, assess their concordance, and examine relationships with sub-clinical atherosclerosis in a rural Indian cohort. We conducted a cross-sectional analysis of 2,465 adults (1,184 men, 1,281 women) aged 40-74 years from the third wave (2010-12) of the Andhra Pradesh Children and Parents Study (APCAPS). Participants with prior CVD were excluded. Ten-year CVD risk was calculated using sex-specific WHO (South Asia) and India-calibrated GLOBORISK models, both laboratory-based (age, sex, smoking, systolic blood pressure, diabetes, total cholesterol) and non-laboratory-based (age, sex, smoking, systolic blood pressure, BMI) algorithms. Categorical agreement was quantified via percentage agreement and quadratic weighted kappa (κ); continuous agreement by Bland-Altman analysis. We also evaluated linear associations between each risk score (categorical and continuous) and three sub-clinical atherosclerosis markers: carotid intima-media thickness (CIMT), pulse-wave velocity (PWV), and augmentation index (AIx), through sex-stratified multi-level linear regression with random intercept at the household level, adjusting for multiple testing (p < 0.01). Median WHO-CVD-risk was 6.0% (IQR 4% - 9%) in men and 3.0% (2% - 4%) in women for both lab and non-lab models; median GLOBORISK-CVD-risk was 12.0% (9% - 16%) for lab-model vs. 15.0% (10% - 16%) for non-lab-model in men and 5.0% (3% - 9%) for lab-model vs. 5.0% (3% - 9%) for non-lab-model in women. Categorical agreement was substantial to almost perfect: WHO κ = 0.82 (overall), GLOBORISK κ = 0.72. Bland-Altman analyses demonstrated mean differences <1% between lab- and non-lab-based scores, though non-lab models underestimated risk by 4.2% in diabetics and 1.2% in participants with total cholesterol ≥200 mg/dL. Both risk scores showed positive, dose-response relationships with CIMT, PWV, and AIx (p-trend<0.001), with each SD increase in CVD-scores associated with clinically meaningful increases in all three markers of sub-clinical atheroscerosis. Non-laboratory-based WHO and GLOBORISK CVD risk scores exhibit high overall agreement with laboratory-based models and correlate strongly with subclinical atherosclerosis in rural India. However, modest underestimation in high-risk subgroups (diabetics, hypercholesterolemia) warrants cautious interpretation. These findings support the feasibility of non-lab risk assessment in resource-constrained settings, while underscoring the need for prospective validation against hard cardiovascular outcomes prior to large-scale implementation.

IntroductionUnderstanding causal risk factors that contribute to the development of multimorbidity is essential for designing and targeting effective preventive strategies. Despite a large body of research in this field, there has been little critical discussion about the appropriateness of the various analytical approaches used. This proposed scoping review aims to summarise and appraise the analytical approaches used in the published literature that evaluated risk factors of multimorbidity and to provide guidance for researchers conducting analyses in this field.Methods and analysisWe will systematically search three electronic databases—Embase, Global Health and MEDLINE, as well as the reference lists of identified relevant review articles, from inception to September 2024. We will screen titles and abstracts using the artificial intelligence-aided software ASReview, followed by screening for eligible articles in full text and extracting data. We will then categorise the analytical approaches used across studies, provide a comprehensive overview of the methodology and discuss the potential strengths and limitations of each analytical approach.Ethics and disseminationWe will undertake a secondary analysis of published literature; therefore, ethical approval is not required. The results will be disseminated through an open-access, peer-reviewed publication. This systematic scoping review will serve as a guide for researchers in selecting analytical approaches for aetiological multimorbidity research, thereby improving the quality and comparability of research in this field.

BackgroundLong covid describes a syndrome of persistent symptoms following COVID-19 and is responsible for substantial healthcare and economic burden. Currently, no effective treatments have been established. Ashwagandha (Withania somnifera (L.) Dunal) is a medicinal herb traditionally used in India for its immune-strengthening and anti-inflammatory properties. Withanolides, a family of steroid-derived molecules unique to Ashwagandha, have been shown to modulate inflammatory pathways in animal models, and several small randomised trials in humans support its effectiveness for reducing symptoms that are also associated with long covid. Therefore, this study aims to assess whether Ashwagandha is effective and safe for improving functional status and reducing symptom burden in adults living with long covid.MethodsA randomised double-blind placebo-controlled trial will be performed at participating general practice (GP) surgeries and long covid clinics across the UK. Individuals diagnosed with long covid will be screened for eligibility and then randomised 1:1 to take 1000 mg daily of Ashwagandha root extract tablets (standardised to <0.9% withanolides) or matching placebo tablets for 3 months (target, n = 2500). Monthly online surveys will be performed to collect patient-reported outcomes, and monthly safety monitoring, including liver function tests, will be conducted by clinical site teams. The primary outcome of the Post-COVID Functional Status Scale score at 3 months will be assessed by baseline-adjusted ordinal logistic regression, according to a pre-published statistical analysis plan. The secondary outcomes included validated quality of life and long covid symptom scales, work status and productivity and adverse events. The trial has been approved as a Clinical Trial of an Investigational Medicinal Produce by the Medicines and Healthcare Regulatory Authority and by the NHS Research Ethics Committee and Health Research Authority.DiscussionTreatments for long covid are urgently needed. This trial will robustly evaluate the safety and efficacy of a candidate treatment with a promising efficacy and safety profile. If found to be effective, the findings will likely influence treatment guidelines and improve health outcomes in those living with long covid.Trial registration numberThis trial was pre-registered on 15/08/2022: ISRCTN12368131

Gait assessment is an important tool for evaluating health risks in older adults but remains underused in low-resource settings. We explored the feasibility of using a low-cost, simple walking protocol with smartphone video capture to extract health-related gait signals by classifying sex and age. Sex and age are fundamental biological factors linked to most health- and aging-related outcomes. Establishing baseline classification performance provides justification for future exploration of more complex health-related conditions using this protocol. This study aimed to assess whether pose parameters derived from smartphone-based gait videos can be used by machine learning models to classify age and sex. A cross-sectional study was conducted with 155 participants (Thailand: n=59, 38.1%; India: n=96, 61.9%). Participants performed a simple walking protocol while being recorded using smartphones. Pose estimation was conducted using the MediaPipe algorithm to extract 109 features related to joint distances, angles, and walking speed. For feasibility assessment, we calculated the proportion of recordings for which pose estimation could be extracted. Elastic-net logistic regression and histogram-based gradient boosting classifiers were used for analysis. Model performance was evaluated using 5-fold cross-validation. Outcomes were sex (male vs female) and age group (aged<65 vs ≥65 y). Pose parameters were successfully extracted from 145 (93.5%) of the 155 video recordings. Among the 145 participants, 94 (64.8%) were female, and 55 (37.9%) were aged 65 years or older. The 2 analytic models demonstrated comparable performance. Sex classification achieved a maximum mean area under the receiver operating characteristic curve of approximately 0.90 (SD 0.06), whereas age classification achieved a maximum mean area under the receiver operating characteristic curve of approximately 0.70 (SD 0.09). Classification performance was primarily influenced by the number of features used, clothing characteristics, and the quality of pose estimation. This simple smartphone-based gait assessment protocol was able to extract meaningful pose parameters and classify biological features (age and sex). Further studies are warranted to evaluate its potential utility for disease screening, risk stratification, and longitudinal health monitoring.

IntroductionThe epidemiological and demographic transitions are leading to a rising burden of multimorbidity (co-occurrence of two or more chronic conditions) worldwide. Evidence on the burden, determinants, consequences and care of multimorbidity in rural and urbanising India is limited, partly due to a lack of longitudinal and objectively measured data on chronic health conditions. We will conduct a mixed-methods study nested in the prospective Andhra Pradesh Children and Parents’ Study (APCAPS) cohort to develop a data resource for understanding the epidemiology of multimorbidity in rural and urbanising India and developing interventions to improve the prevention and care of multimorbidity.Methods and analysisWe aim to recruit 2100 APCAPS cohort members aged 45+ who have clinical and lifestyle data collected during a previous cohort follow-up (2010–2012). We will screen for locally prevalent non-communicable, infectious and mental health conditions, alongside cognitive impairments, disabilities and frailty, using a combination of self-reported clinical diagnosis, symptom-based questionnaires, physical examinations and biochemical assays. We will conduct in-depth interviews with people with varying multimorbidity clusters, their informal carers and local healthcare providers. Deidentified data will be made available to external researchers.Ethics and disseminationThe study has received approval from the ethics committees of the National Institute of Nutrition and Indian Institute of Public Health Hyderabad, India and the London School of Hygiene and Tropical Medicine, UK. Meta-data and data collection instruments will be published on the APCAPS website alongside details of existing APCAPS data and the data access process (www.lshtm.ac.uk/research/centres-projects-groups/apcaps).

Women live on average five years longer than men, and the sex difference in longevity is typically lower in populations with high mortality. South Africa-a high mortality population with a large sex disparity-is an exception, but the causes of death that contribute to this difference are not well understood. Using data from a demographic surveillance system in rural KwaZulu-Natal (2000-2014), we estimate differences between male and female adult life expectancy by HIV status. The contribution of causes of death to these life expectancy differences are computed with demographic decomposition techniques. Cause of death information comes from verbal autopsy interviews that are interpreted with the InSilicoVA tool. Adult women lived an average of 10.4 years (95% confidence Interval 9.0-11.6) longer than men. Sex differences in adult life expectancy were even larger when disaggregated by HIV status: 13.1 (95% confidence interval 10.7-15.3) and 11.2 (95% confidence interval 7.5-14.8) years among known HIV negatives and positives, respectively. Elevated male mortality from pulmonary tuberculosis (TB) and external injuries were responsible for 43% and 31% of the sex difference in life expectancy among the HIV negative population, and 81% and 16% of the difference among people living with HIV. The sex differences in adult life expectancy in rural KwaZulu-Natal are exceptionally large, atypical for an African population, and largely driven by high male mortality from pulmonary TB and injuries. This is the case for both HIV positive and HIV negative men and women, signalling a need to improve the engagement of men with health services, irrespective of their HIV status.

Tranexamic acid, given within 3 h of birth, reduces bleeding deaths in women with postpartum haemorrhage. We examined whether giving tranexamic acid shortly after birth can prevent postpartum haemorrhage in women with moderate or severe anaemia. This international, randomised, double-blind, placebo-controlled trial was done in 34 hospitals across four countries (Nigeria, Pakistan, Tanzania, and Zambia). We recruited women of any age in active labour with moderate or severe anaemia (haemoglobin <100 g/L). We randomly assigned women (1:1) who had given birth vaginally to receive 1 g of tranexamic acid or matching placebo by slow intravenous injection (over 10 min) within 15 min of the umbilical cord being cut or clamped. Women were randomly assigned by selection of the lowest numbered treatment pack from a box containing 20 packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to group assignment. The primary outcome was a clinical diagnosis of primary postpartum haemorrhage, which might be an estimated blood loss of more than 500 mL or any blood loss sufficient to compromise haemodynamic stability within 24 h of randomisation, analysed on an intention-to-treat basis. Safety analyses were performed in all participants included in the intention-to-treat population. This trial was registered on ISRCTN (ISRCTN62396133), ClinicalTrials.gov (NCT03475342), and the Pan African Clinical Trial Registry (PACTR201909735842379) and is closed to recruitment. From Aug 24, 2019, to Sept 19, 2023, 16 586 women aged 14–50 years were invited to take part and 1518 were excluded. 7580 women were randomly assigned to receive tranexamic acid and 7488 to receive placebo. Primary outcome data were unavailable for one woman in each group. The median time interval from the start of the administration of the trial treatment to the diagnosis of postpartum haemorrhage was 18·5 min (IQR 5–58); 20 min (8–64) in women with moderate anaemia and 13 min (7–44) in women with severe anaemia. 358 (35%) of 1024 with postpartum haemorrhage for whom time data were available were diagnosed before the trial treatment had been fully administered. Clinically diagnosed postpartum haemorrhage occurred in 530 (7·0%) of 7579 in the tranexamic acid group and in 497 (6·6%) of 7487 in the placebo group (risk ratio [RR] 1·05, 95% CI 0·94–1·19). There was no strong evidence against the null hypothesis of homogeneity of effects for any of the prespecified subgroup analyses: severity of anaemia (p=0·44), antepartum haemorrhage (p=0·044), birth canal trauma (p=0·37), use of pain control (p=0·37), and baseline risk of postpartum haemorrhage (p=0·31). There were no vascular occlusive events (pulmonary embolism, deep vein thrombosis, stroke, and myocardial infarction) reported in either group. There were no adverse events related to the treatment and no treatment-related deaths. In women with moderate and severe anaemia, giving tranexamic acid within 15 min of the umbilical cord being clamped did not reduce the risk of clinically diagnosed postpartum haemorrhage. The Bill & Melinda Gates Foundation and the Wellcome Trust.

BackgroundSouth Asians are at an increased risk of premature cardiovascular disease, but the reasons for this are unclear. Poor socio-economic conditions in childhood are associated with an increased risk of cardiovascular disease in many high-income countries and may be particularly relevant to South Asia, where socio-economic deprivation is more prevalent and severe. However, evidence from South Asia is limited.MethodsWe pooled data from two large population-based studies in India to provide a geographically representative and adequately powered sample of Indian adults. We used multilevel linear regression models to assess associations between standard of living index (SLI) in childhood (measured by recalled household assets at age 10–12 years) and major cardiovascular risk factors including adiposity, blood pressure, and fasting blood lipids, glucose and insulin.ResultsData on 14 011 adults (median age 39 years, 56% men) were analysed. SLI in childhood was inversely associated with systolic and diastolic blood pressure, independent of socio-economic conditions in adulthood, with beta coefficients (95% CIs) of −0.70 mmHg (−1.17 to −0.23) and −0.56 mmHg (−0.91 to −0.22), respectively, per SD increase in SLI in childhood. There was no strong evidence for an association between SLI in childhood and other risk factors of cardiovascular disease.ConclusionsPoor socio-economic conditions in childhood may contribute to the increased risk of premature cardiovascular disease among South Asians by raising their blood pressure. Elucidating the mechanisms and improving socio-economic conditions for children in South Asia could provide major reductions in the burden of cardiovascular disease.

Aim: Meat is commonly consumed in India; however, in comparison to Western settings, it is eaten in relatively lower quantities and with minimal processing. The association between meat intake and cardio-metabolic diseases (CMDs) and their risk factors in India is currently uncertain. We examined whether meat intake is associated with risk factors for CMDs and the measures of subclinical atherosclerosis in urbanising villages in southern India. Methods: We conducted a cross-sectional analysis of 6012 adults (52.3% male) participating in the Andhra Pradesh Children and Parents’ Study (APCAPS), which is a large prospective, intergenerational cohort study in Southern India that began with the long-term follow-up of the Hyderabad Nutrition Trial (1987–1990). We used cross-sectional data from the third wave of data collection conducted in 2010–2012, where total meat intake was assessed using 100-item, semi-quantitative validated food frequency questionnaires (FFQ). The FFQs were validated using multiple weighed 24 h dietary recalls. The main predictor, ‘total meat intake’, was calculated as the sum of chicken, red meat, and fish consumption. The risk factors for CMDs [systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), waist circumference (WC), fasting glucose, total cholesterol, homeostasis model assessment insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, and C-reactive protein] and measures of subclinical atherosclerosis [Carotid Intima-Media Thickness, Pulse Wave Velocity, and Augmentation Index] were assessed using standardised clinical procedures. Stratified by gender, the association of meat intake with the risk factors of CMDs and measures of subclinical atherosclerosis was examined using linear multilevel models with random intercept at the household level. Results: The mean (SD) age of the male (n = 3128) and female participants (n = 2828) was 34.09 years (15.55) and 34.27 years (12.73), respectively. The median (IQR) intake of meat was 17.79 g/day (8.90, 30.26) in males and 8.90 g/day (4.15, 18.82) in females. In males, a 10 g increase in total meat intake/1000 Kcal/day was positively associated with DBP, BMI, WC, total cholesterol, LDL-C, and triglycerides, whereas in females, a 10 g increase in total meat intake/1000 Kcal/day was positively associated with SBP, DBP, fasting glucose, HOMA-IR, total cholesterol, LDL-C, and triglycerides. There was no relationship between meat consumption and measures of subclinical atherosclerosis. Conclusions: Meat intake had a linear positive association with CMD risk factors among the relatively younger Indian population who were consuming meat at lower levels compared to their European counterparts.