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Understanding Inequalities in Cancer Survival Using Bayesian Machine Learning
No full textMost cancer patients are diagnosed after the age of 60, often with existing chronic health conditions (comorbidities), that can delay diagnosis and complicate treatment, prognosis, and monitoring. These comorbidities may exacerbate existing sociodemographic inequalities in cancer survival. While much research has focused on how comorbidities affect overall survival, national and international institutions typically prefer the relative survival framework for population-based studies. This framework decomposes an individual’s overall hazard into a known population hazard and an excess hazard attributable to cancer. Estimands derived from the excess hazard, such as net survival, are widely used to assess interventions and inform policy. In this article, we use a Bayesian machine learning approach to estimate the excess hazard and identify vulnerable subgroups with a higher excess hazard, using Bayesian additive regression trees (BART). We develop a proportional hazards version of BART for the relative survival context and extend it to accommodate nonproportional hazards. We also provide tools for model interpretation and posterior summarization. This is applied to colon cancer data from England to provide insights when paired with state-of-the-art data linkage methods. We then identify drivers of inequalities in cancer survival through variable importance quantification. Supplementary materials for this article are available online, including a standardized description of the materials available for reproducing the work
Untangling the fragmented landscape of extreme heat services and warning systems
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Extreme heat warning systems are expanding globally, yet remain conceptually fragmented and operationally diverse. With a myriad of heat indices in use and limited guidance on their purpose or performance, countries risk adopting ineffective systems misaligned with local risks and decision-making needs. This Perspective traces the roots of this fragmentation across disciplinary, operational, and institutional lines, showing how differing approaches from health, meteorology, and climate science have led to incompatible definitions and thresholds. We then propose a clear typology of heat indices, aligned with WMO guidance: (1) temperature indicators, (2) thermal indices, and (3) heatwave intensity indices. The typology clarifies what each type measures, where it performs best, and the trade-offs involved, helping systems move toward greater transparency, coherence, and fit-for-purpose. Each type offers distinct strengths, and many countries will benefit from layered approaches that combine them. Moving toward intensity-based approaches represents a conceptual shift, from identifying hot days to quantifying the severity of heatwaves. By aligning early warning systems with this understanding, countries can improve coordination, reduce health and societal impacts, and accelerate progress under global frameworks such as the UN’s Early Warnings for All initiative
A Machine Learning Model Integrating Remote Sensing, Ground Station, and Geospatial Data to Predict Fine-Resolution Daily Air Temperature for Tuscany, Italy.
Get PDFHeat-related morbidity and mortality are increasing due to climate change, emphasizing the need to identify vulnerable areas and people exposed to extreme temperatures. To improve heat stress impact assessment, we developed a replicable machine learning model that integrates remote sensing, ground station, and geospatial data to estimate daily air temperature at a spatial resolution of 100 m × 100 m across the region of Tuscany, Italy. Using a two-stage approach, we first imputed missing land surface temperature data from MODIS using gradient-boosted trees and spatio-temporal predictors. Then, we modeled daily maximum and minimum air temperatures by incorporating monitoring station observations, satellite-derived data (MODIS, Landsat 8), topography, land cover, meteorological variables (ERA5-land), and vegetation indices (NDVI). The model achieved high predictive accuracy, with R2 values of 0.95 for Tmax and 0.92 for Tmin, and root mean square errors (RMSE) of 1.95 °C and 1.96 °C, respectively. It effectively captured both temporal (R2: 0.95; 0.94) and spatial (R2: 0.92; 0.72) temperature variations, allowing for the creation of high-resolution maps. These results highlight the potential of integrating Earth Observation and machine learning to generate high-resolution temperature maps, offering valuable insights for urban planning, climate adaptation, and epidemiological studies on heat-related health effects
Carbon sedimentation in shallow floodplain lakes
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Shallow lakes are increasingly recognized as important sites for organic carbon (OC) storage. However, the drivers of OC deposition in shallow floodplain lakes remain unclear due to complex terrestrial and aquatic interactions. Using 8 yr of monthly sediment trap data in a cross‐ecosystem experiment on six UK shallow lakes of varying riverine connectivity, we investigated the role of allochthonous (fluvial materials) vs. autochthonous (phytoplankton production) deposits as the OC supply to lake sediments. Organic carbon sedimentation rates in river‐connected (1.3 ± 1.2 g C m−2 d−1, mean ± SD) and isolated lakes (0.5 ± 0.4 g C m−2 d−1) surpassed those previously published for temperate zone eutrophic lakes. Generalized linear mixed‐effect models identified water column chlorophyll a as the best predictor of OC sedimentation for most lakes, suggesting that autochthonous phytoplankton production was the dominant driver of OC sedimentation, albeit stimulated by riverine nutrient supply. Carbon (C) transfer to the sediments was modulated by flow; during major floods, phytoplankton was likely flushed out of lakes, reducing OC sedimentation. Inorganic carbon sedimentation intermittently contributes substantially to carbon deposition in spring, summer, and winter. This study evidenced that shallow floodplain lakes are important sites for C deposition, with maximum C transfer to the sediments during the growing season. Future increases in hydrological variability could negatively impact the capacity of shallow floodplain lakes to retain and sequester carbon
Associations of ambient exposure to benzene, toluene, ethylbenzene, and xylene with daily mortality: a multicountry time-series study in 757 global locations.
No full textBACKGROUND: The presence of benzene, toluene, ethylbenzene, and xylene isomers (BTEX) in the environment is of increasing concern due to their toxicity and ubiquity. Although the adverse health effects of BTEX exposure have been documented, robust epidemiological evidence from large-scale, multicountry studies using advanced exposure assessment methodologies remains scarce. We aimed to assess the association of short-term ambient exposure to individual BTEX components and their mixture with daily total, cardiovascular, and respiratory mortality on a global scale. METHODS: Daily data on mortality, meteorological factors, and air pollution were collected from 757 locations across 46 countries or regions. Data on individual chemicals (ie, benzene, toluene, xylenes [summation of ethylbenzene, m-xylene, p-xylene, and o-xylene]) and the aggregate mixture (ie, BTEX) were estimated using a chemistry-climate model. We examined the short-term associations of each individual chemical as well as the BTEX mixture with daily total, cardiovascular, and respiratory mortality in a multicountry framework. Using a two-stage time-series design, we first applied generalised additive models with a quasi-Poisson distribution to obtain location-specific associations, which were subsequently pooled using random-effects meta-analysis. Two-pollutant models were used to assess the independent effects of BTEX after adjusting for co-pollutants (PM2·5, PM10, nitrogen dioxide, sulphur dioxide, ozone, and carbon monoxide). Additionally, we assessed the overall exposure-response curves with spline terms. FINDINGS: An IQR increment of BTEX concentration on lag 0-2 days (3-day moving average of the present day and the previous 2 days) was associated with increases of 0·57% (95% CI 0·49-0·65), 0·42% (0·30-0·54), and 0·68% (0·50-0·86) in total, cardiovascular, and respiratory mortality, respectively. The corresponding effect estimates for an IQR increment in individual chemicals (benzene, toluene, and xylenes) were 0·38-0·61%, 0·44-0·70%, and 0·41-0·65%, respectively. The associations remained significant after adjusting for co-pollutants, with a general decline in magnitude, except for a slight increase after adjustment for ozone. The shape of the exposure-response curves for all pollutants and causes of death was almost linear, with steeper slopes at low concentrations and no discernible thresholds. INTERPRETATION: This global study provides novel evidence linking short-term exposure to ambient BTEX, both individually and as a mixture, with increased daily total, cardiovascular, and respiratory mortality. Our findings underscore the need for comprehensive air pollution mitigation policies, including stringent controls on BTEX emissions, to protect public health. FUNDING: Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China, Shanghai Municipal Science and Technology Major Project, Shanghai B&R Joint Laboratory Project, and Shanghai International Science and Technology Partnership Project
Streptococcus intermedius: an underestimated pathogen in brain infection?
Get PDFStreptococcus intermedius is an oral commensal organism belonging to the Streptococcus anginosus group (SAG). S. intermedius causes periodontitis as well as invasive, pyogenic infection of the central nervous system, pleural space or liver. Compared with other SAG organisms, S. intermedius has a higher mortality as well as a predilection for intracranial infection, suggesting it is likely to possess virulence factors that mediate specific interactions with the host resulting in bacteria reaching the brain. The mechanisms involved are not well described. Intracranial suppuration (ICS) due to S. intermedius infection can manifest as an abscess within the brain parenchyma, or a collection of pus (empyema) in the sub- or extra-dural space. These infections necessitate neurosurgery and prolonged antibiotic treatment and are associated with a considerable burden of morbidity and mortality. The incidence of ICS is increasing in several settings, with SAG species accounting for an increasing proportion of cases. There is a paucity of published literature regarding S. intermedius pathogenesis as well as few published genomes, hampering molecular epidemiological research. This perspective evaluates what is known about the clinical features and pathogenesis of ICS due to S. intermedius and explores hypothetical explanations why the incidence of these infections may be increasing
Xpert MTB/RIF Cycle Threshold as a Marker of Tuberculosis (TB) Disease Severity: Implications for TB Treatment Stratification.
Get PDFBACKGROUND: Recent trials have demonstrated that shortened 4-month treatment durations are effective for the majority of people with tuberculosis (TB). However, there is a population of patients with TB who require longer treatment durations. Prospectively identifying those who require shorter versus longer treatment durations would support evaluation and implementation of optimized regimens. METHODS: We analyzed data from the RIFASHORT TB treatment-shortening noninferiority trial to define a TB phenotype classification. The RIFASHORT trial primary outcome was reanalyzed using the protocol-defined noninferiority criterion of 8 percentage points, stratifying by those classified as having limited or extensive disease. RESULTS: Xpert MTB/RIF semiquantitative bacterial burden in combination with TB disease involvement grading on chest X-ray achieved the strongest differentiation between relapse and nonrelapse. The extensive disease TB phenotype (high semiquantitative bacterial burden and extensive TB disease on X-ray) accounted for one-quarter of the RIFASHORT trial population and more than half of all posttreatment TB relapses (13/23). For the limited TB disease phenotype (a semiquantitative bacterial burden other than high or no extensive TB disease on X-ray), the experimental 4-month 1200-mg rifampicin-containing regimen met the protocol-defined noninferiority criterion in both modified intention-to-treat (adjusted risk difference: -1.3%; 95% CI, -6.7% to 4.0%) and per protocol analyses (1.7%; 95% CI, -3.8% to 7.1%). CONCLUSIONS: The TB phenotype classification derived here successfully identified three-quarters of RIFASHORT trial participants for whom a 4-month 1200-mg rifampicin regimen was noninferior to the 6-month standard of care. A definitive phase III randomized trial of disease-stratified rifampicin-based TB treatment is justified
Mifepristone Access Through Community Pharmacies When Regulated as a Routine Prescription Medication.
Get PDFIMPORTANCE: The mifepristone-misoprostol medication abortion regimen became available in Canada as a normally prescribed medication, without restrictions, in 2017. Despite rapid uptake, patients have reported difficulty accessing this time-sensitive medication. OBJECTIVE: To quantify mifepristone availability within 3 calendar days at community pharmacies. DESIGN, SETTING, AND PARTICIPANTS: This population-based, cross-sectional study using a mystery caller survey was conducted from July to August 2024 at community pharmacies in British Columbia (BC), Canada. EXPOSURE: Surveyor posing as a patient with a prescription for mifepristone who requests to pick up the medication within 3 calendar days. For nondispensing pharmacies (ie, unable to dispense within 3 days), surveyors requested a referral to a dispensing pharmacy. MAIN OUTCOMES AND MEASURES: Proportion of pharmacies that could dispense mifepristone or provide a valid referral to a dispensing pharmacy; proportion of reproductive-aged (15-49 years) female population residing within 15-minute walking and 15-, 30-, and 60-minute driving times of a dispensing pharmacy, and proportion of the population with poor local availability (<50% of available pharmacies dispense mifepristone). RESULTS: Among 1460 of 1482 community pharmacies, 962 (66%) could dispense mifepristone within 3 days and 169 (12%) provided a valid referral. Only one-third of nondispensing pharmacies (169 of 498 pharmacies [34%]) provided a valid referral to a dispensing pharmacy; 329 pharmacies (23%) neither dispensed within 3 days nor provided a valid referral. Almost all reproductive-aged females (1 095 915 of 1 110 218 females [99%]) in BC lived within a 15-minute drive of a mifepristone-dispensing pharmacy. Urban pharmacies were more likely to be nondispensing and nonreferring (relative risk [RR], 1.78; 95% CI, 1.19-2.80) and less likely to offer same-day dispensing (RR, 0.39; 95% CI, 0.30-0.51) compared with rural pharmacies. Populations in areas with the most residential instability (RR, 1.41; 95% CI, 1.19-1.67) or greater ethnocultural diversity (RR, 1.36; 95% CI, 1.15-1.61) had poorer local availability of mifepristone-dispensing pharmacies. CONCLUSIONS AND RELEVANCE: This cross-sectional study found 99% of reproductive-aged BC females lived within a 15-minute drive of a mifepristone-dispensing pharmacy; however, despite relatively good geographic coverage and mifepristone being available as a routine prescription, 23% of pharmacies neither dispensed within 3 days nor provided a valid referral, putting the onus on patients to identify a dispensing pharmacy. These findings may inform policy and initiatives to enhance pharmacist referral networks and improve mifepristone access, as well as service planning for international jurisdictions considering a similar medication abortion framework
The experience of trial participation disclosure among sex workers in a phase IIb HIV vaccine trial: A qualitative study in urban Tanzania.
Get PDFGlobally, HIV vaccine clinical trials are conducted in the quest for an effective preventive vaccine. Volunteers' participation is vital to the success of these trials. However, disclosing involvement in a vaccine trial may have significant consequences, potentially affecting key aspects such as recruitment, retention, and overall engagement. This study aimed to explore the experiences of disclosure and non-disclosure of participation in a Phase IIb HIV Vaccine Trial among female sex workers in Dar es Salaam, Tanzania, and used a descriptive qualitative design. Fifteen in-depth interviews and four focus group discussions were conducted among volunteers who were participating in the HIV vaccine trial. Data analysis was done manually using the framework method. Three themes emerged: reasons for disclosure, reasons for non-disclosure, and consequences of disclosure. Reasons for disclosure were grouped into two categories: intended disclosure and unintended disclosure. Intended disclosure occurred to seek support for trial participation and to share information within trusted relationships. Unintended disclosure arose from circumstances related to trial participation. Reasons for non-disclosure had two categories: perceived lack of understanding about trial participation and concerns about inadequate support. Consequences of disclosure encompassed three categories: uncertainty about the vaccine's side effects, the perception of volunteers being infected with HIV, and disapproval of the vaccine trial. The findings reveal that volunteers experienced a complex interplay between disclosure and non-disclosure of their participation in the PrEPVacc trial. The key themes - reasons for disclosure, non-disclosure, and consequences of disclosure - underscore the importance of understanding the personal and social factors influencing these decisions. These insights highlight the need for enhanced community education and support mechanisms to address concerns, mitigate misconceptions, and improve participation in HIV vaccine trials. Trial Registration: This study was conducted as part of a multicenter phase IIb three-arm, two-stage HIV prophylactic vaccine trial with Registration Number NCT04066881, accessible at https://clinicaltrials.gov/study/NCT04066881
Global, regional, and national trends in routine childhood vaccination coverage from 1980 to 2023 with forecasts to 2030: a systematic analysis for the Global Burden of Disease Study 2023.
Get PDFBACKGROUND: Since its inception in 1974, the Essential Programme on Immunization (EPI) has achieved remarkable success, averting the deaths of an estimated 154 million children worldwide through routine childhood vaccination. However, more recent decades have seen persistent coverage inequities and stagnating progress, which have been further amplified by the COVID-19 pandemic. In 2019, WHO set ambitious goals for improving vaccine coverage globally through the Immunization Agenda 2030 (IA2030). Now halfway through the decade, understanding past and recent coverage trends can help inform and reorient strategies for approaching these aims in the next 5 years. METHODS: Based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, this study provides updated global, regional, and national estimates of routine childhood vaccine coverage from 1980 to 2023 for 204 countries and territories for 11 vaccine-dose combinations recommended by WHO for all children globally. Employing advanced modelling techniques, this analysis accounts for data biases and heterogeneity and integrates new methodologies to model vaccine scale-up and COVID-19 pandemic-related disruptions. To contextualise historic coverage trends and gains still needed to achieve the IA2030 coverage targets, we supplement these results with several secondary analyses: (1) we assess the effect of the COVID-19 pandemic on vaccine coverage; (2) we forecast coverage of select life-course vaccines up to 2030; and (3) we analyse progress needed to reduce the number of zero-dose children by half between 2023 and 2030. FINDINGS: Overall, global coverage for the original EPI vaccines against diphtheria, tetanus, and pertussis (first dose [DTP1] and third dose [DTP3]), measles (MCV1), polio (Pol3), and tuberculosis (BCG) nearly doubled from 1980 to 2023. However, this long-term trend masks recent challenges. Coverage gains slowed between 2010 and 2019 in many countries and territories, including declines in 21 of 36 high-income countries and territories for at least one of these vaccine doses (excluding BCG, which has been removed from routine immunisation schedules in some countries and territories). The COVID-19 pandemic exacerbated these challenges, with global rates for these vaccines declining sharply since 2020, and still not returning to pre-COVID-19 pandemic levels as of 2023. Coverage for newer vaccines developed and introduced in more recent years, such as immunisations against pneumococcal disease (PCV3) and rotavirus (complete series; RotaC) and a second dose of the measles vaccine (MCV2), saw continued increases globally during the COVID-19 pandemic due to ongoing introductions and scale-ups, but at slower rates than expected in the absence of the pandemic. Forecasts to 2030 for DTP3, PCV3, and MCV2 suggest that only DTP3 would reach the IA2030 target of 90% global coverage, and only under an optimistic scenario. The number of zero-dose children, proxied as children younger than 1 year who do not receive DTP1, decreased by 74·9% (95% uncertainty interval 72·1-77·3) globally between 1980 and 2019, with most of those declines reached during the 1980s and the 2000s. After 2019, counts of zero-dose children rose to a COVID 19-era peak of 18·6 million (17·6-20·0) in 2021. Most zero-dose children remain concentrated in conflict-affected regions and those with various constraints on resources available to put towards vaccination services, particularly sub-Saharan Africa. As of 2023, more than 50% of the 15·7 million (14·6-17·0) global zero-dose children resided in just eight countries (Nigeria, India, Democratic Republic of the Congo, Ethiopia, Somalia, Sudan, Indonesia, and Brazil), emphasising persistent inequities. INTERPRETATION: Our estimates of current vaccine coverage and forecasts to 2030 suggest that achieving IA2030 targets, such as halving zero-dose children compared with 2019 levels and reaching 90% global coverage for life-course vaccines DTP3, PCV3, and MCV2, will require accelerated progress. Substantial increases in coverage are necessary in many countries and territories, with those in sub-Saharan Africa and south Asia facing the greatest challenges. Recent declines will need to be reversed to restore previous coverage levels in Latin America and the Caribbean, especially for DTP1, DTP3, and Pol3. These findings underscore the crucial need for targeted, equitable immunisation strategies. Strengthening primary health-care systems, addressing vaccine misinformation and hesitancy, and adapting to local contexts are essential to advancing coverage. COVID-19 pandemic recovery efforts, such as WHO's Big Catch-Up, as well as efforts to bolster routine services must prioritise reaching marginalised populations and target subnational geographies to regain lost ground and achieve global immunisation goals. FUNDING: The Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance