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paramix: An R package for parameter discretisation in compartmental models, with application to calculating years of life lost.
Get PDFCompartmental infectious disease models are used to calculate disease transmission, estimate underlying rates, forecast future burden, and compare benefits across intervention scenarios. These models aggregate individuals into compartments, often stratified by characteristics to represent groups that might be intervention targets or otherwise of particular concern. Ideally, model calculation could occur at the most demanding resolution for the overall analysis, but this may be infeasible due to availability of computational resources or empirical data. Instead, detailed population age structure might be consolidated into broad categories such as children, working-age adults, and seniors. Researchers must then discretise key epidemic parameters, like the infection-fatality ratio, for these lower resolution groups. After estimating outcomes for those crude groups, follow-on analyses, such as calculating years of life lost (YLLs), may need to distribute or weight those low-resolution outcomes back to the high resolution. The specific calculation for these aggregation and disaggregation steps can substantially influence outcomes. To assist researchers with these tasks, we developed paramix, an R package which simplifies the transformations between high and low resolution. We demonstrate applying paramix to a common discretisation analysis: using age structured models for health economic calculations comparing YLLs. We compare how estimates vary between paramix and several alternatives for an archetypal model, including comparison to a high resolution benchmark. We consistently found that paramix yielded the most similar estimates to the high-resolution model, for the same computational burden of low-resolution models. In our illustrative analysis, the non-paramix methods estimated up to twice as many YLLs averted as the paramix approach, which would likely lead to a similarly large impact on incremental cost-effectiveness ratios used in economic evaluations
Potential impact, costs, and benefits of population-wide screening interventions for tuberculosis in Viet Nam: A mathematical modelling study.
Get PDFPopulation-wide screening may accelerate the decline of tuberculosis (TB) incidence, but the optimal screening algorithm and duration must weigh resource considerations. We calibrated a deterministic transmission model to TB epidemiology in Viet Nam. We simulated three population-wide screening algorithms from 2025: sputum nucleic acid amplification tests (NAAT, Xpert MTB/RIF Ultra) only; chest radiography (CXR) followed by NAAT; and CXR-only without microbiological confirmation. We determined the annual screening rounds required to reduce pulmonary TB prevalence below 50 per 100,000 people. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs), representing the additional costs (in US1 each. NAAT-based algorithms required at least six rounds to reach the prevalence threshold, while CXR-only required three. NAAT-only achieved a prevalence reduction consistent with the ACT3 trial after three rounds. The CXR+NAAT algorithm averted 4.29m DALYs (95%UI:2.86-6.14) at US161m (95%UI:111-224) annually during the intervention resulted in average annual cost savings of US1 led to a 50% and 15% reduction in budget impact and a 63% and 26% reduction in the estimated ICER for the NAAT-only and CXR+NAAT algorithms, respectively. In Viet Nam, population-wide screening could achieve ambitious policy goals. Substantial front-loaded investment is immediately followed by persistent cost savings and could be further offset by more affordable NAATs
Impact of COVID-19 on unmet needs for healthcare in Peru: an interrupted time series analysis.
Get PDFThe COVID-19 pandemic affected people's health and access to healthcare worldwide. Still, little is known about how distinct phases of the pandemic - namely the lockdown period and the period directly after lockdown - impacted these outcomes, and whether there were differences in these impacts among different segments of the Peruvian population. The aim of this study was to examine the impact of different phases of the COVID-19 response on unmet needs for healthcare across Peru. Using an interrupted time series design, this study analyzed quarterly data from Peru's National Household Survey on Living Conditions and Poverty (ENAHO) from 2018 to 2022. Outcome variables included people reporting having a health problem in the last 4 weeks and, among those reporting a problem, whether they had needed and sought care. These outcomes were stratified by demographic characteristics (i.e., by age group, gender, disability, indigenous status, regions, and rural/urban). Step and trend changes in outcomes during and directly after lockdown periods were compared to the pre-pandemic period. Overall, the prevalence of health problems decreased by 18.4 percentage points (pp) during the lockdown period compared to pre-pandemic levels, although unmet healthcare needs increased by 16.7 pp. Once lockdowns were removed, prevalence of health problems and access to healthcare increased slightly, but remained below pre-pandemic levels. Certain groups, namely people with disabilities, indigenous people and people in rural areas, had persistently worse health and poorer access to care. Persistent disparities in unmet healthcare needs highlight the necessity of targeted interventions to address systemic barriers faced by vulnerable populations and ensure continuity of care during health crises
BactiVac, the Bacterial Vaccines Network.
Get PDFBacterial vaccines save lives and constitute a major tool to address the challenge of anti-microbial resistance, though, despite their success, there is a relative paucity of such vaccines. Historically there has not been a network that focuses on bacterial vaccines, to promote sharing of approaches and best practices, and provide advocacy. BactiVac, the Bacterial Vaccines Network, was established in August 2017 to address this gap. Its mission is to advance vaccine development against global bacterial infections in humans and animals, to reduce disease, death, and antimicrobial resistance, and thereby enhance economic development. BactiVac brings together academia, industry, policymakers and funders from high-income countries (HICs) and low- and middle-income countries (LMICs), in a network of 2060 members from 92 countries, including 51 % from LMICs and 15 % from industry. BactiVac supports vaccine development through Catalyst Project Awards and Catalyst Training Awards. This funding targets bottlenecks and capacity-building in vaccinology, particularly among LMIC early-career researchers. Annual Network Meetings facilitate exchange of information and ideas, and new collaborations. We provide advocacy for bacterial vaccines nationally and internationally and, by partnering with aligned networks, function as a network within a network of networks. Therefore, through providing financial support and facilitating collaboration, BactiVac supports and enhances the bacterial vaccinology community to help reduce the devastating burden of disease caused by bacterial infections
Circulating cardiovascular biomarkers in motion: redefining cardiovascular risk with dynamic prediction.
Get PDFCurrent approaches to estimate cardiovascular risk for primary prevention of cardiovascular disease (CVD) are suboptimal and novel strategies that optimise and personalise risk predictions are needed. In this review, we provide an overview of the potential use of circulating cardiovascular biomarkers - C-reactive protein, growth differentiation factor 15, N-terminal pro B-type natriuretic peptide, and cardiac troponins - to improve CVD risk prediction in the general population. We present novel statistical approaches that dynamically capture risk to further optimise and personalise cardiovascular risk estimation systems. While all studied cardiovascular biomarkers are independently associated with CVD risk when using measurements from a single time-point, the added value they provide to traditional risk factors in terms of accuracy is modest. A dynamic risk prediction approach - such as joint modelling - that can incorporate changes in biomarkers and other risk factors over time may better capture the complexities of CVD development, enhancing CVD risk estimates. With the increasing adoption of electronic health records and commercially available assays for these circulating biomarkers, deploying such systems in clinical practice has become feasible. Future research should focus on the development and validation of multi-marker biomarker-driven dynamic risk prediction models, along with development of a standardized methodological approach for comparing performance of dynamic risk estimation systems against current static models. To facilitate its implementation in clinical practice, public health impact and cost-effectiveness needs to be assessed. Finally, optimizing screening intervals through a biomarker-driven dynamic risk approach may offer further improvement in individualising primary CVD prevention strategies
Determinants of geographic variation in the incidence of adult nonmalignant meningioma in the United States, 2010-2019.
Get PDFBACKGROUND: US incidence rates of nonmalignant brain tumors are 3-fold higher in highest versus lowest incidence states. A county-level analysis was conducted to assess whether geographic variation in nonmalignant meningioma (NMM) incidence is related to demographics, cancer registry, health care, and other factors.
METHODS: Age-adjusted incidence rates of NMM in US counties during 2010-2019 were modeled with data from the Central Brain Tumor Registry of the United States. Demographic, geographic, cancer registry, environmental, health care, health, lifestyle, and socioeconomic factors at the county level were drawn from numerous data sources. Bayesian index regression models were fit containing spatial random effects.
RESULTS: Three domains were significantly associated with rates of NMM at the county level: cancer registry practices (funding source and % radiographically confirmed), socioeconomic status index (higher levels with percent working in white-collar occupations as an important contributor), and demographics (% Black and % female). No associations were observed for general health or environmental factors. In the fully adjusted model, the number of counties with significantly elevated and lowered spatial random effects decreased by 33% and 28%, respectively, compared to a no-covariate model.
CONCLUSIONS: Although general health and environmental factors cannot be ruled out in explaining the geographic variation in NMM incidence rates, results suggest that socioeconomic factors, certain demographic characteristics, and cancer diagnosis and registry practices may all play a significant role in driving such variation. These results may have implications for other tumor types diagnosed primarily radiographically or outside hospital settings, where variation in detection and reporting may affect incidence rates
Effect of Brazil's national human papillomavirus vaccination programme on the incidence of cervical cancer and cervical intraepithelial neoplasia grade 3 in women aged 20-24 years: a population-based study.
Get PDFBACKGROUND: Studies from high-income countries have shown significant reductions in cervical cancer and cervical intraepithelial neoplasia grade 3 (CIN3) after implementing the human papillomavirus (HPV) vaccination. However, evidence from low-income and middle-income countries remains limited. Therefore, we aimed to evaluate the impact of the Brazilian HPV vaccination programme on the incidence of cervical cancer and CIN3.
METHODS: In this population-based study, we analysed cervical cancer and CIN3 incidence among women aged 20-24 years between 2019 and 2023, using data from the diagnosis, treatment, and hospitalisations (ie, admittance to hospital) databases from Brazil. Birth cohorts were categorised according to the year of birth. The primary outcome was the diagnosis of cervical cancer (ICD-10 code C53) and CIN3 (code D06). Incidence rate ratios were estimated using Bayesian negative binomial regression, adjusting for calendar year, age, and trimester of diagnosis. We used breast cancer as a negative control outcome. The main analysis was conducted using the data from the Painel Oncologia (diagnosis and treatment database).
FINDINGS: We analysed 60·6 million women-years of follow-up for women aged 20-24 years. 1318 cervical cancer and 2132 CIN3 cases were recorded. The incidence rate ratios comparing the 2001-03 birth cohort to the 1994-98 birth cohort were 0·42 (95% credible interval 0·27-0·66) for cervical cancer and 0·33 (0·20-0·53) for CIN3. The negative control outcome and exposure showed values close to the null with wider credible intervals. Sensitivity analyses using hospitalisation data showed similar results.
INTERPRETATION: Brazil's HPV vaccination programme reduced cervical cancer and CIN3 incidence in women aged 20-24 years. These findings underscore the vaccine's potential to reduce health disparities and contribute to the elimination of cervical cancer in low-income and middle-income populations.
FUNDING: Royal Society and Conselho Nacional de Desenvolvimento Científico e Tecnológico
The Good School Toolkit-Secondary to prevent violence against students: a pilot cluster randomised controlled trial.
Get PDFBACKGROUND: Schools provide a unique opportunity to address multiple forms of violence against adolescents. Yet, few whole-school interventions to comprehensively address physical, sexual and emotional violence against adolescents from multiple perpetrators have been evaluated in the Global South. We report results of a pilot trial of the Good School Toolkit-Secondary (GST-S), an intervention for secondary schools in Uganda. The trial aimed to determine whether criteria for progression to a phase 3 trial were met based on pre-specified implementation and research feasibility criteria.
METHODS: We conducted a pilot cluster randomised controlled trial with two arms and parallel assignment. The trial was conducted in eight secondary schools, varying by faith status and urban or rural setting, randomly selected from a list of all eligible registered schools in Kampala and Wakiso Districts. Schools were randomised to control or intervention arms and aware of their allocation. The primary outcome was to determine whether criteria for progression to a phase 3 trial were met based on pre-specified criteria regarding fidelity, acceptability and understanding of GST-S, and research feasibility. Outcomes were measured using cross-sectional baseline and endline surveys among eligible school students and staff, and routine monitoring data collected during implementation.
RESULTS: Overall, seven of eight schools agreed to participate in the baseline survey, randomisation and endline survey, with three randomised to the control and four to the intervention group. The endline survey included 837 students (response rate: control, 100%; intervention, 99.4%) and 98 staff (response rate: control, 91.1%; intervention, 95.0%). There were delays to the trial due to Covid-19 and an Ebola outbreak. Despite this, all pre-specified implementation and feasibility criteria were met. The intervention was acceptable and understandable to students and staff, was delivered with fidelity, and the trial demonstrated good research feasibility.
CONCLUSIONS: We present the first evidence that it is feasible to deliver a whole-school intervention aiming to address physical, sexual and emotional violence against adolescents from multiple perpetrators including peers, teachers and intimate partners in sub-Saharan Africa. Based on our results, we recommend progression to a phase 3 trial with minor refinements to the research methods and intervention.
TRIAL REGISTRATION: Pan African Clinical Trials Registry, PACTR202009826515511, 16/09/20
Measured and self-reported hypertension among women of reproductive age, Gambia, Kenya, Mozambique.
Get PDFPROBLEM: In sub-Saharan Africa, hypertension prevalence is usually estimated from participant recall. We assessed the accuracy of self-reported hypertension in women of reproductive age.
APPROACH: In PRECISE (PREgnancy Care Integrating translational Science, Everywhere), an observational prospective cohort study, we recruited 1825 non-pregnant women of reproductive age, 610 in the Gambia, 609 in Kenya and 606 in Mozambique. We compared self-reported and measured hypertension (systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90mmHg). We adjusted hypertension prevalence for age, body mass index, education, parity, and antihypertensive medicine and oral contraceptive use.
LOCAL SETTING: PRECISE was conducted in both urban and rural hospitals or clinics.
RELEVANT CHANGES: The women were generally in their late twenties and parous. Adjusted measured hypertension prevalence was higher in Mozambique (10.4%; 95% confidence interval, CI: 7.9-12.7) and the Gambia (9.3%; 95% CI: 6.6-12.6) than in Kenya (4.6%; 95% CI: 3.0-6.6). Self-reported hypertension prevalence was highest in the Gambia (12.9%; 95% CI: 10.2-15.9) versus Mozambique (4.2%; 95% CI: 2.8-5.7) or Kenya (6.7%; 95% CI: 5.0-8.6). Sensitivity of self-reported (versus measured) hypertension was less than 45% in all countries, with specificities more than 89%. Positive likelihood ratios were fair in the Gambia (3.70; 95% CI: 2.47-5.54), and good in Kenya (5.79; 95% CI: 3.36-9.98) and Mozambique (5.18; 95% CI: 2.56-10.46). All negative likelihood ratios were poor (≥ 0.20).
LESSONS LEARNT: Self-reported hypertension is unsuitable for population hypertension estimates among women of reproductive age in these countries
Association of Increase in White Matter Hyperintensity Volume With Rate of Hippocampal Atrophy in a Population-Based Study of Aging.
Get PDFBACKGROUND AND OBJECTIVES: Higher white matter hyperintensity volume (WMHV) is associated with hippocampal atrophy, cognitive decline, and dementia; however, it is unknown whether continually increasing WMHV is related to hippocampal atrophy. The aim of this study was to determine whether higher WMHV change rate (WMHVR) is related to higher hippocampal atrophy rate (HAR); this relationship is dependent on cardiovascular risk factors (CVRFs), Alzheimer disease (AD) pathology, and genetic risk; and this relationship is mediated by neuroaxonal degradation.
METHODS: Participants from Insight46, a substudy of the 1946 British Birth Cohort, underwent combined [18F] florbetapir PET/MRI scans at University College London approximately 2.5 years apart. WMHVR was quantified from T2/fluid-attenuated inversion recovery and HAR from T1 sequences. Life-course blood pressure and CVRF data were measured at 6 and 3 time points, respectively. APOE genotype and neurofilament light chain (NfL) quantification were derived from blood samples. Participants with neurologic conditions were excluded from primary analyses. Linear regression was used to test the relationships between WMHVR and HAR, adjusting for sex, age, and total intracranial volume (TIV) and CVRF, APOE-ε4 status, and β-amyloid (Aβ) in separate models. Semipartial R2 was calculated from these models. In a post hoc analysis, structural equation modeling aimed to determine whether NfL mediated the relationship between WMHVR and HAR.
RESULTS: A total of 317 individuals without neurologic conditions (48% female, 100% White British, mean baseline age [SD] = 70.5 [0.6] years) were included. The mean HAR was 0.04 [0.04] mL/y. Each 1 mL/y increase in WMHVR was associated with a 0.014 mL/y (95% CI 0.005-0.022) increase in HAR, adjusted for TIV, age, and sex (p = 0.002). Adjustment for additional variables did not meaningfully attenuate this association (≥0.012 mL/y, p ≤ 0.005, all models), and there was no indirect effect through NfL (0.0004 mL/y [95% CI -0.0006 to 0.0012], p < 0.1).
DISCUSSION: Higher WMHVR was associated with HAR between approximately 70 and 73 years, independent of CVRF levels, APOE-ε4 status, and Aβ load, and not mediated by markers of neuroaxonal degradation. Although AD-specific pathology is typically considered the main cause of accelerated HAR, we demonstrated that HAR is also linked to deteriorating WM health. These results will need to be replicated in more diverse cohorts with longer follow-up periods to confirm the findings