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Long-term exposure to outdoor fine particulate and physical activity with mortality and cardiovascular events: an analysis of the Prospective Urban Rural Epidemiology (PURE)-China cohort study
Get PDFBackgroundLong-term exposure to PM2.5 and low physical activity are independently associated with an increased risk of cardiovascular disease (CVD). However, there is limited research investigating the combined effects of PM2.5 exposure and physical activity on CVD risk. This study aims to explore these interactions related to CVD and mortality.MethodsWe analysed data from the PURE-China cohort, including 39,970 adults aged 35–70 years, with a median follow-up of 11.9 years. PM2.5 exposure was estimated using a Bayesian hierarchical model. Physical activity was quantified using metabolic equivalent task (MET)-minutes per week. The primary outcome was a composite of all-cause mortality and major cardiovascular events. Cox frailty models and restricted cubic splines were used to assess associations. Interaction effects were evaluated using measures of multiplicative and additive interaction, including the relative excess risk due to interaction (RERI) and the proportion attributable to interaction (AP).FindingsParticipants were divided into high and low PM2.5 exposure groups by the median concentration (47.70 μg/m3). In low-exposure areas, higher total physical activity significantly reduced the risk of composite outcome (HR: 0.84, 95% CI: 0.73–0.97, p trend = 0.012) and major cardiovascular events (HR: 0.80, 0.67–0.95, p trend = 0.022). However, in high-exposure regions, physical activity showed no protective effect for the composite outcome (HR: 0.97, 0.85–1.09, p trend = 0.551) and major cardiovascular events (HR: 0.98, 0.85–1.13, p trend = 0.864). Higher non-recreational physical activity reduced the risks of composite outcome and major CVD in low-exposure areas but provided no benefit in high-exposure regions (p interaction = 0.011, 0.024, respectively). Significant antagonistic interaction was observed between high PM2.5 exposure and low non-recreational physical activity for the composite outcome (RERI: −0.215, 95% CI: −0.406 to −0.024; AP: −0.155, 95% CI: −0.294 to −0.017).InterpretationLong-term exposure to high PM2.5 concentrations diminishes the cardiovascular benefits of physical activity, particularly non-recreational activities. These findings underscore the need for tailored physical activity guidelines and air quality interventions in heavily polluted regions to maximize public health benefits.<p/
Impact of Vgsc-1014 mutations on the feeding pattern of Phlebotomus argentipes
Get PDFKnockdown resistance alleles (kdr alleles) within the para voltage-gated sodium channel gene (Vgsc) are a common mechanism of DDT and pyrethroid resistance in insect vectors. In the primary Asian visceral leishmaniasis vector, Phlebotomus argentipes, two kdr alleles in codon 1014 of the Vgsc are associated with insecticide resistance, potentially presenting challenges to vector control efforts in the Indian subcontinent. Here, we screened Vgsc-1014 alleles and blood meal origin in P. argentipes females collected between September 2013 and August 2015 in Bangladesh (Mymensingh), to understand how Vgsc-1014 alleles could impact feeding patterns. The sand fly collection took place in parallel with the vector control agency’s biannual indoor residual spraying (IRS) programme. In this region, the wild-type leucine (wt-leucine) was the most common allele (66.7%), followed by the mutant serine (19.4%) and phenylalanine alleles (13.9%). Only 55 sand fly blood meals (13%) came from humans, with most of bovine origin (61%). However, sand flies that had fed on humans showed strongly contrasting Vgsc-1014 genotypic frequencies compared to those feeding on other blood sources. Whilst most (81%) P. argentipes with human blood possessed kdr genotypes with two mutant alleles, most (81%) sand flies feeding on other blood sources possessed genotypes with wt-leucine alleles (P<0.001). Significant spatial variation in kdr frequencies was detected, but there was no clear temporal trend nor effect of sampling year on any results, and no significant impact of recent IRS in any analyses. The association between human feeding and kdr alleles in parallel with pyrethroid spraying indicates a new mechanism of how kdr alleles might impact VL control programs.</p
A cluster-randomized trial of interventions for adolescent mental disorders in Zimbabwe
Get PDFPurpose: Young people have low uptake of mental health. We compared two task-shifted mental health care models, i.e., adult Friendship Bench (FB) delivered by community health workers and Youth Friendship Bench (YouFB) delivered by trained university students in Harare, Zimbabwe. We hypothesised that the peer-delivered YouFB would have greater uptake and effectiveness in managing common mental disorders (CMDs) in 16–19-year-olds compared to the standard FB model. We also aimed to evaluate the reach, fidelity, acceptability and cost of the YouFB compared to standard FB. Methods: We conducted an open-label cluster-randomised, hybrid type-2 implementation trial with cost analysis in 26 primary care clinics and their surrounding communities. Facilities were randomised 1:1 to FB or YouFB. The primary implementation outcome was uptake, defined as the proportion of adolescents aged 16–19 offered FB sessions for treatment of CMD who completed at least one FB session. Secondary implementation outcomes included reach, fidelity, and acceptability. The main clinical outcome was the clinical effectiveness of YouFB vs. FB at six months, assessed by changes in Shona Symptom Questionnaire (SSQ-14) scores. We also carried out a cost analysis from a societal perspective. Acceptability was evaluated qualitatively using in-depth interviews. Reach was calculated as the number of adolescents receiving FB sessions per clinic day. Results: Uptake in the FB and YouFB arms was 86.6% (187/216) and 95.6% (220/230), respectively (primary outcome). The number of completed FB sessions (feasibility) was higher in the YouFB arm than the FB arm (cluster-level mean prevalence 96.7% vs. 85.8%, prevalence ratio = 1.13; 95% CI:0.98–1.30). Among 528 trial participants, adjusting for baseline score, gender, education, marital status, employment and HIV status, the proportion of participants with SSQ-14 score ≥ 8 was similar by arm after six months, adjusted odds ratio = 0.65 (95% CI: 0.36–1.17). Total program costs were higher in the YouFB arm. Process evaluation found the YouFB to be highly acceptable. Conclusions: A youth-focused Friendship Bench intervention is feasible and acceptable. Recipients highly valued the ability to connect with a same-age peer and its easy accessibility. However, further intervention optimisation is needed to improve its clinical and cost-effectiveness. Trial registration: This trial was prospectively registered on 21/08/2018 with the Pan African Clinical Trial Registry database. Registration no PACTR201808181810124.</p
Molnupiravir or nirmatrelvir–ritonavir plus usual care versus usual care alone in patients admitted to hospital with COVID-19 (RECOVERY):a randomised, controlled, open-label, platform trial
Get PDFBackground: Molnupiravir and nirmatrelvir–ritonavir are oral antivirals that have shown efficacy in preventing disease progression in outpatients with COVID-19. We aimed to evaluate these treatments for patients hospitalised with COVID-19 pneumonia, for whom data on these antivirals are scarce. Methods: The RECOVERY trial is a randomised, controlled, open-label, adaptive platform trial testing treatments for COVID-19. In this study we report the molnupiravir and nirmatrelvir–ritonavir comparisons from the RECOVERY trial. In each comparison, participants aged 18 years and older were randomly allocated (1:1) to the relevant antiviral (5 days of molnupiravir 800 mg twice daily or 300 mg nirmatrelvir and 100 mg ritonavir twice daily) in addition to usual care, or to usual care alone. The molnupiravir comparison was conducted at 75 hospitals in the UK, two in Nepal, and two in Indonesia; the nirmatrelvir–ritonavir comparison was conducted at 32 hospitals in the UK. Participants could take part in both comparisons. The primary outcome was 28-day mortality, and secondary outcomes were time to discharge alive from hospital and progression to invasive ventilation or death. Analysis was by intention to treat. Both comparisons were stopped because of low recruitment. This study is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: From Jan 24, 2022, to May 24, 2023, 923 participants were recruited to the molnupiravir comparison (445 allocated to molnupiravir and 478 to usual care), and from March 31, 2022, to May 24, 2023, 137 participants were recruited to the nirmatrelvir–ritonavir comparison (68 allocated to nirmatrelvir–ritonavir and 69 to usual care). More than three-quarters of participants were vaccinated and had antispike antibodies at randomisation, and more than two-thirds were receiving other SARS-CoV-2 antivirals. In the molnupiravir comparison, 74 (17%) participants allocated to molnupiravir and 79 (17%) allocated to usual care died within 28 days (hazard ratio [HR] 0·93 [95% CI 0·68–1·28], p=0·66). In the nirmatrelvir–ritonavir comparison, 13 (19%) participants allocated to nirmatrelvir–ritonavir and 13 (19%) allocated to usual care died within 28 days (HR 1·02 [0·47–2·23], p=0·96). In neither comparison was there evidence of any difference in the duration of hospitalisation or the proportion of participants progressing to invasive ventilation or death.Interpretation: Adding molnupiravir or nirmatrelvir–ritonavir to usual care was not associated with improvements in clinical outcomes. However, low recruitment meant a clinically meaningful benefit of treatment could not be ruled out, particularly for nirmatrelvir–ritonavir. Funding: UK Research and Innovation (UK Medical Research Council), the National Institute for Health and Care Research, and the Wellcome Trust.</p
Eliciting initial programme theories for a health research capacity strengthening initiative targeting African universities: A realist synthesis
Get PDFThere is a growing call for theory-driven evaluation approaches to health research capacity strengthening (HRCS) interventions. Specifically, realist evaluation has gained wide attention given its response to the question: How does an intervention work, why, for whom and under what conditions? In realist evaluation, initial programme theories (IPTs) are first elicited before they are tested and refined. This article describes the IPTs of an HRCS programme aimed at strengthening the research capacity of African universities. Using the ‘Developing Excellence in Leadership, Training and Science (DELTAS Africa) programme as a real-world case, the IPTs were drafted through a review of the programme documents and other published literature. Seven programme documents and 32 published papers covering 26 research capacity strengthening initiatives in African universities were reviewed. Different Context, Mechanism and Outcomes (CMO) were extracted and CMO configurations were formulated. Thereafter, the CMO configurations were refined through four interviews with the DELTAS programme designing team. Three transferrable IPTs were elicited. Evidence suggests that, for HRCS interventions to be more effective in strengthening research capacity in African universities, systemic challenges (e.g., lack of funding for health research, ineffective research policy environment and lack of institutional support for research) need to be addressed and the university staff/ researchers empowered, incentivised and motivated. The article underscores the importance of institutional buy-in, effective implementation of research policies (e.g., protected time, research career pathways, gender equality, research ethics and integrity, anti-bullying and anti-harassment, etc.), long-term research funding and equitable research partnerships in fostering a strong research environment and culture. Notably, the article makes a methodological contribution by demonstrating how IPTs can be developed using disparate evidence sources. The IPTs will be tested and refined through a primary realist evaluation, which will further refine the CMOs presented in this article and provide insights into the current HRCS evaluation framework
Long-Term Outcomes of BAV-0 Patients Compared With BAV-1 and TAV Patients After TAVR
Get PDFBackground: Differences in long-term clinical outcomes following transcatheter aortic valve replacement (TAVR) in different anatomical subtypes of aortic valve stenosis (AS), specifically tricuspid aortic valves (TAV) and bicuspid aortic valves (BAV) of types 0 (BAV-0) and 1 (BAV-1), are not well understood. Objectives: The authors sought to report and compare the long-term clinical outcomes among patients with different anatomical subtypes of AS undergoing TAVR. Methods: We conducted an international retrospective cohort study involving patients who underwent TAVR for severe AS at 3 large, high-volume heart centers in China, Germany, and Denmark before October 2018. Five-year follow-up ended on October 30, 2023, and the primary endpoint was all-cause mortality. Results: A total of 2,553 AS patients (BAV-0: n = 134; BAV-1: n = 305; TAV: n = 2,114) who underwent TAVR more than 5 years ago were included. The mean age of this cohort was 79.9 ± 6.8 years, and the median Society of Thoracic Surgeons score was 3.6% [Q1-Q3: 2.4%-5.4%]. The median follow-up time was 3.24 years (Q1-Q3: 1.25-5.00 years). At 5 years, BAV-1 (adjusted HR: 2.38 [95% CI: 1.32-4.28]; P = 0.004) and TAV (adjusted HR: 3.02 [95% CI: 1.71-5.31]; P < 0.001) had a higher risk for all-cause mortality after TAVR compared with BAV-0. BAV patients who were treated with balloon-expandable valves had a higher long-term all-cause mortality (41.7% [28.5%-52.5%] vs 23.6% [17.9%-28.8%]; HR: 1.63 [95% CI: 1.05-2.51]; P = 0.028) compared with those with self-expanding valves. Conclusions: Among patients with severe AS undergoing TAVR, BAV-0 was associated with a better long-term prognosis compared with TAV and BAV-1.</p
Protocol for the Redefining Maternal Anemia in Pregnancy and Postpartum (ReMAPP) study: A multisite, international, population-based cohort study to establish global hemoglobin thresholds for maternal anemia
Get PDFBackground. Anemia affects one in three pregnant women worldwide, with the greatest burden in South Asia and sub-Saharan Africa. During pregnancy, anemia has been linked to an increased risk of adverse maternal and neonatal health outcomes. Despite widespread recognition that anemia can complicate pregnancy, critical gaps persist in our understanding of the specific causes of maternal anemia and the cutoffs used to diagnose anemia in each trimester and in the postpartum period. Methods and analysis. The Redefining Maternal Anemia in Pregnancy and Postpartum (ReMAPP) study is a multisite, prospective, cohort study nested within the Pregnancy Risk, Infant Surveillance, and Measurement Alliance (PRISMA) Maternal and Newborn Health study. Research sites are located in Kenya, Ghana, Zambia, India, and Pakistan. Participants are up to 12,000 pregnant women who provide serial venous blood samples for hemoglobin assessment at five time points: at <20 weeks, 20 weeks, 28 weeks, and 36 weeks gestation and at six weeks postpartum. We will use two analytical approaches to estimate hemoglobin thresholds for defining anemia: (1) clinical decision limits for cutoffs in each trimester and at six weeks postpartum based on associations of hemoglobin levels with adverse maternal, fetal, and neonatal health outcomes and (2) reference limits for gestational-week-specific cutoffs and at six weeks postpartum for mild, moderate, and severe anemia based on tail statistical percentiles of hemoglobin values in a reference (i.e., clinically healthy) subpopulation. We will also conduct biomarker-intensive testing among a sub-sample of participants in each trimester to explore underlying contributing factors of maternal anemia. Ethics and dissemination. The study received local and national ethical approvals from all participating institutions. Findings from multisite analyses will be published among open-access, peer-reviewed journals and disseminated with local, national, and international partners. Strengths and limitations.• Novel study design to allow multiple analytical approaches (clinical decision limits and reference limits) in the same population to establish hemoglobin thresholds. • Use of gold standard methods and external quality assurance programs to ensure harmonized hemoglobin measurement across sites. • Inclusion of biomarker-intensive study arm to examine the etiology of anemia among pregnant women. • All data is contributed by populations historically underrepresented in research in low- and middle-income countries.</p
The effect of follow-up reexamination on the long-term prognosis of patients with acute coronary syndrome undergoing coronary angiography
Get PDFBackground: Patients with acute coronary syndrome (ACS) remain at high risk for recurrent adverse cardiovascular events after discharge. Patient adherence to secondary prevention is poor. This study proposes a follow-up center-based secondary prevention program to assess whether a structured cardiologist-led follow-up and reexamination protocol influences ACS patient prognosis.Methods: A total of 9,534 ACS patients undergoing coronary angiography were retrospectively included and divided into a reexamination group (n = 6,804) and a non-reexamination group (n = 2,730) according to whether they were reexamined within one year or not. The patients were followed up after discharge for 3 years, and clinical outcomes were recorded. The primary outcome was cardiac death. Results: Reexamination within 12 months was significantly associated with a reduced risk of cardiac death (adjusted hazard ratio [aHR], 0.58; 95% confidence interval [CI], 0.44–0.75) at 3 years after ACS. Among patients who underwent reexamination, the risk of cardiac death was 50% lower (aHR, 0.50; 95% CI, 0.35–0.70) and 63% lower (aHR, 0.37; 95% CI, 0.20–0.67) in the high-frequency (more than or equal to 2 times within one year) and long-term (continued reexamination after the first year of follow-up) reexamination groups, respectively. Similar results were observed after propensity score matching analysis. Conclusions: Participation in a structured follow-up and reexamination programme significantly reduces the risk of cardiac death among ACS survivors. Establishing a follow-up center could be of great significance in improving patient prognoses.</p
A broader lens on tuberculosis cost-effectiveness analysis: How patient-incurred costs and post-tuberculosis outcomes reshape estimates in a multi-country study
Get PDFTuberculosis (TB) remains a major public health challenge, with financial and health impacts extending beyond treatment. Both the perspective adopted in cost-effectiveness analyses—which critically determines choices such as the inclusion of patient-incurred costs—and the extent to which long-term post-treatment considerations are incorporated have important policy implications. This study examines how the choice of timeframe and cost perspectives influence the estimated cost-effectiveness of TB interventions, particularly preventative measures. Using data from 19 WHO TB patient cost surveys and global epidemiological databases, we modelled a hypothetical preventative TB intervention, generating four incremental cost-effectiveness ratios (ICERs) per country under different analytical approaches. These included a conventional timeframe up to treatment completion, an extended timeframe incorporating post-TB effects, and two perspectives that either included or excluded patient-incurred costs. The approach yielding the lowest ICER (societal perspective; extended timeframe) was anchored in the primary analysis to a 1×GDP per capita threshold. Using this benchmark simplified cross-country comparisons and removed the need for health system cost estimates. Sensitivity and scenario analyses explored how threshold values influenced the relative impact of timeframe and costing perspective. ICERs were higher when patient costs were omitted or the post-TB period was excluded, peaking when both were absent. However, across all countries, post-TB considerations had a far greater impact on cost-effectiveness. On average, removing the post-TB period increased ICERs by over 50% (ranging from +19.3% in Ghana to +108% in Mongolia, societal perspective). Including patient-incurred costs increased the likelihood that prevention was cost-effective, particularly in low-GDP settings with lower willingness-to-pay thresholds. However, their impact was minimal above 2×GDP. Our study highlights how narrowly defining the financial and health burden of tuberculosis in cost-effectiveness analyses risks underestimating the benefits of interventions—particularly in lower-GDP countries where the socioeconomic burden of tuberculosis is greatest—which could lead to misguided policy decisions that overlook the full impact of tuberculosis
Evaluation of the effectiveness of a restricted diet therapy package combining standardised caloric intake with exercise in obese patients: A 12-month randomised controlled trial.
No full textObjectives to background and aims: Obesity is a major global health challenge associated with increased risks of diabetes and cardiovascular disease. Although calorie restriction and exercise are cornerstone strategies for weight management, long-term adherence remains difficult in real-world settings. This randomised controlled trial aimed to evaluate the effectiveness of a structured calorie-restricted dietary therapy package combined with exercise in achieving weight loss and improving metabolic and psychological outcomes among obese adults. Methods: In this 12-month, parallel-group randomised controlled trial, 99 obese adults were randomly assigned to an intervention group (standardised meal kit + exercise) or a control group (standard dietary advice + exercise). Weight, glucose, lipid profiles, and mental health outcomes were assessed at baseline, 3, 6, and 12 months. LASSO regression was used to identify predictors of successful weight loss, and linear mixed-effects models evaluated associations between percentage weight loss and changes in glycaemic, lipid, and psychosocial outcomes. Results: By month 12, all participants in the intervention group achieved ≥5 % weight loss, with 59.18 % achieving ≥10 %, compared to 38.00 % and 6.00 % in the control group, respectively. Group assignment was the strongest predictor of weight loss success, followed by HDL levels and family history of obesity. Each 1 % reduction in body weight was significantly associated with lower FPG, 2hPG, TC, TG, and LDL-C, as well as improved SDS, SAS, and SF-36 scores. These associations remained significant after adjusting for confounders. However, interaction analyses showed no significant between-group differences in the effect of weight loss on outcomes. Conclusion: A standardised dietary therapy package combining calorie restriction and exercise is a feasible and effective strategy to achieve clinically meaningful weight loss and improve metabolic and psychological health in obese adults. Although both groups experienced improvements, the structured intervention enhanced adherence and overall effectiveness.</p