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Reply to the commentary of Burkhard Madea and Elke Doberentz on our article "An assessment of the Henssge method for forensic death time estimation in the early post-mortem interval".
Get PDFA predictive model is developed to forecast an outcome of interest within a target population based on the characteristics of the cases. The model aims to identify key factors associated with the outcome of interest to achieve a high degree of agreement between observed and predicted outcome values (i.e. model precision). For models that seek to predict the time since death, the target population includes individuals who died at a crime scene, as predicting the time since death is especially relevant in these instances. The Henssge model, based on the work of Marshall and Hoare [2], was developed using a cohort of individuals who were not reported to have died at a crime scene and for whom a known time since death was established, comprising a convenience sample of 39 bodies from corpses admitted to an Institute of Legal Medicine in Germany (cases of sudden death in public an hospital cases [3, 4]). Furthermore, model development was conducted without external validation steps, making it prone to overfitting
Assessing the risk of diseases with epidemic and pandemic potential in a changing world.
Get PDFHow do human activities contribute to the emergence of zoonotic diseases that can lead to epidemics and pandemics? Our analysis of common drivers of the World Health Organization's priority diseases suggests that climate conditions, including higher temperatures, higher annual precipitation levels, and water deficits, elevate the risk of disease outbreaks. In addition, land-use changes, human encroachment on forested areas, increased population and livestock density, and biodiversity loss contribute to this risk, with biodiversity loss showing a complex and nonlinear relationship. This study also presents a global risk map and an epidemic risk index that combines countries' specific risk with their capacities for preparing and responding to zoonotic threats
Impact of distribution of facemasks on community incidence and outcomes of COVID-19: A cluster randomised trial in India.
Get PDFBACKGROUND: Randomised evidence on the effectiveness of delivering facemasks for reducing the health impact of COVID-19 remains limited. METHODS: We conducted a cluster randomised trial in Telangana, India, in August-November 2020 to investigate whether distribution and promotion of facemasks in villages reduces the incidence and adverse outcomes of COVID-19. We randomised 20 villages from the ongoing APCAPS surveillance study (1:1 ratio) to village-wide distribution of 3-layer cloth facemasks along with promotional messaging, or no intervention. Outcomes were incidence of notified COVID-19 (primary), hospitalised COVID-19 and all-cause mortality (secondary), collected through household surveillance by village health workers. Mask wearing was assessed through standardised observations in village centres. Data were analysed by multilevel Poisson regression. FINDINGS: Use of the study facemasks and any face coverings in public spaces was higher in intervention villages (19% and 59%, respectively) than control villages (0% and 38%). In the 10 intervention (N=16,741 adults) and 10 control villages (N=15,278 adults), respectively, the crude incidence per thousand person months (number of events) of notified COVID-19 was 2.15 (n=144) and 2.45 (n=150), of hospitalised COVID-19 was 0.07 (n=5) and 0.21 (n=13), and of all-cause mortality was 0.91 (n=61) and 1.10 (n=67). In models accounting for age, sex and pre-intervention COVID-19 rate, rate ratios in intervention versus control villages were 0.96 (95% confidence interval 0.57-1.63) for COVID-19 cases, 0.36 (0.12-1.05) for COVID-19 hospitalisations, and 0.84 (0.55-1.29) for all-cause mortality. No adverse effects were reported. INTERPRETATION: We are unable to draw firm conclusions about the effect of village-wide distribution and promotion of facemasks on COVID-19 incidence from these data due to a low number of events leading to imprecise effect estimates. Nonetheless, our findings are consistent with the modest protective effect on incident cases seen in previous randomised trials, extending these to adverse outcomes for the first time. REGISTRATION: The trial was pre-registered on the Clinical Trials Registry of India on 25/07/2020 (CTRI/2020/07/026796)
Disparate co-evolution and prevalence of sulfadoxine and pyrimethamine resistance alleles and haplotypes at dhfr and dhps genes across Africa.
Get PDFSulfadoxine-pyrimethamine (SP), despite emergence of mutations in dhfr and dhps genes associated with lower treatment efficacy, is still recommended for preventive malaria treatment. Therefore, it is important to understand the evolution of P. falciparum dhfr and dhps genes. We used the MalariaGEN Pf7 dataset to describe haplotype frequencies across 22 African countries, including changes over time in The Gambia, Mali, Ghana, and Kenya. We show that the triple mutant of dhfr, N51I/C59R/S108N, has remained the dominant haplotype across the continent with limited evidence of additional mutations. There is greater variation for dhps in terms of haplotype diversity and spatial heterogeneity of haplotypes found across Africa. Although samples from Madagascar have low genetic differentiation from samples from mainland East Africa at the whole genome level, we show that dhps K540E is highly differentiated between the two populations, being at very low frequency in Madagascar (4%). Whole genome data reveal 12 SNPs which are also highly differentiated between Madagascar and East Africa, including aat1 and a possible novel drug resistance locus approximately 20 kb 3' of mdr1. We highlight the value of longitudinal sampling and whole genome sequence data for understanding the heterogeneity and ongoing changes in anti-malarial drug resistance genetic markers
Trial emulation to assess the effect of surgery on survival when there are competing risks, with application to patients with thoracic aortic aneurysms.
Get PDFOBJECTIVES: This study extends methods to estimate average causal effect of aneurysm repair surgery on (i) overall survival and (ii) aneurysm-related mortality, accounting for competing risks using data from the Effective Treatment for Thoracic Aortic Aneurysm (ETTAA) cohort. STUDY DESIGN AND SETTING: ETTAA, a prospective cohort study, recruited 886 patients between 2014 and 2018. Patients were linked to UK national hospital and mortality databases by National Health Service digital and followed-up for later surgeries and deaths. We compared a strategy of open or endovascular surgery (whichever appropriate) within 12 months of enrollment to ETTAA with no surgery within 12 months using the trial emulation framework and cloning-censoring-weighting (CCW) analysis. Key confounders at baseline were controlled for using inverse probability weighting methods. RESULTS: In complete case analysis, if everyone received surgery within a 12-month grace period, an estimated 7-year survival probability was 57.4% (95% CI: 47.3%, 67.4%) vs 49.9% (44.0%, 55.0%) if no one received surgery. This benefit was primarily attributable to reduction in aneurysm-related deaths (difference -8.7%, 95% CI: -14.0%, -3.9%), with no significant effect on deaths from other causes. The findings were consistent under sensitivity analyses, including multiple imputation of missing confounders. Our CCW approach addressed selection-for-treatment, allowed for surgery to be received within a grace period, and used appropriate methods to separate aneurysm-related mortality from competing risks. CONCLUSION: The study demonstrates the utility of trial emulation and counterfactual methods in estimation of causal effects on competing risks using observational data. The findings suggest a benefit for aneurysm-related survival up to 7 years after enrollment. PLAIN LANGUAGE SUMMARY: This study shows how to estimate effects of surgery on different causes of death, when we cannot do a clinical trial, and illustrates this using an example from heart surgery. The aorta is the main artery that carries oxygen-rich blood from the heart to the body. In some people, a part of the vessel wall becomes weak and loses its elastic properties, so it doesn't return to its normal shape after the blood has passed through. This can lead to swelling or bulging in the aorta, called an aneurysm. A thoracic aortic aneurysm, or TAA for short, is an aneurysm in the section of the aorta in the chest (https://www.bhf.org.uk/informationsupport/conditions/thoracic-aortic-aneurysm). We have used data from the Effective Treatment for Thoracic Aortic Aneurysm (ETTAA) study, which investigated aneurysm growth rates, patient outcomes, quality of life, and costs, in 886 patients diagnosed with TAA. ETTAA compared two surgical treatments, Open Heart Surgery, where the section of the aorta that contains the aneurysm is removed and replaced by a new aorta made from a synthetic material, and Stent Grafting, where tubes are inserted into arteries to allow blood to flow freely using less invasive "keyhole" surgery. ETTAA reviewed existing research evidence but data comparing the effectiveness of these two approaches to each other and to outcomes without surgery were of sparse or limited quality and outdated. The results of ETTAA up to 2020 have been published in a monograph. (https://pubmed.ncbi.nlm.nih.gov/35094747/). Two findings from ETTAA motivated this study. First, there were no clinical trials comparing surgery with no surgery and no studies that mimic clinical trials. Second, we had not considered whether surgery overall prevents deaths due to aneurysm or deaths from other causes. We call these two types of death, competing risks. It is unlikely that a clinical trial comparing surgery with no surgery will ever be completed because the number of people who are diagnosed with TAA is small. Also, TAA can become a serious problem if left untreated. On the other hand, surgery for TAA is difficult and can result in serious complications, including death. Therefore, it is important to know how much surgery improves survival related to the aneurysm and whether it improves survival overall. Recent developments in statistics provided methods for investigating survival in a way which increases confidence in the cause-effect relationship between surgery and outcomes. In this study, we show how these statistical methods can be used to estimate the proportion of patients who die from the competing risks, if all patients had surgery within 12 months compared with if no patients had surgery within 12 months. We take into account the different times between diagnosis of TAA and surgery and adjust for the main differences between surgery and no surgery patients. Using these methods, we estimate that surgery reduces deaths due to aneurysms at 7 years by 8.7%, with no effect on deaths from other causes. The benefit of surgery was significant by 3 years after diagnosis. We also provide discussion about using routine medical records to repeat this type of study
Modelling extensions for multi-location studies in environmental epidemiology.
Get PDFMulti-location studies are increasingly used in environmental epidemiology. Their application is supported by designs and statistical techniques developed in the last decades, which however have known limitations. In this contribution, we propose an improved modelling framework that addresses these issues. Specifically, this flexible framework allows the direct modelling of demographic differences across locations, defining geographical variations linked to multiple vulnerability factors, capturing spatial heterogeneity and predicting risks to new locations, and improving the assessment of uncertainty. We illustrate these new developments in an analysis of temperature-mortality associations in Italian cities, providing fully reproducible R code and data
Phylogenetic insights into the early spread of the SARS-CoV-2 Alpha variant across Europe.
Get PDFThe evolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has profoundly influenced the trajectory of the COVID-19 pandemic. In late 2020, the Alpha variant (Pango lineage B.1.1.7) emerged in South East England, characterized by enhanced transmissibility, increased mortality, and rapid geographic expansion. Here, we studied the evolutionary history and migration dynamics of Alpha across Europe using genomic data sourced from 38 European countries. Our findings reveal that Alpha was introduced to over 25 European countries within 90 days of its emergence, with the UK accounting for 61% of early exportation events. However, as the epidemic progressed, several mainland European countries, including France, Denmark, and the Czech Republic, became significant hubs of onward transmission. Social mixing during the December holiday period and air travel facilitated the variant's rapid dissemination, as corroborated by air passenger flight volumes and viral introductions. Notably, genomic surveillance intensified after Alpha was designated a variant of concern, reducing the detection lag in countries with later introductions. Our study highlights the critical interplay between international mobility, surveillance efforts, and regional connectivity in shaping the epidemiology of SARS-CoV-2 variants and underscores the need for coordinated genomic surveillance and timely interventions to mitigate the spread of emerging pathogens
Eating habits and sociodemographic factors impact household dietary greenhouse gas emissions reduction in Great Britain
Get PDFDietary changes can substantially reduce greenhouse gas emissions in Great Britain. Guidelines recommend reducing meat and dairy consumption while increasing plant-based foods, but household purchasing habits achieving these shifts are not well understood. Here we analysed food purchase data from ~30,000 British households (2012–2019), identifying 709 households that reduced their dietary greenhouse gas emissions by 34%. Using latent class analysis, we identified two distinct clusters among these households: plant-based adopters who reduced meat and dairy, adopting healthier diets; and households replacing meat with dairy and convenience foods, showing less healthy dietary changes. Plant-based adopters typically had higher education, higher incomes, were older (45+ years), and smaller in size. Households shifting toward dairy and convenience foods were older and smaller. Supporting healthy and sustainable diets requires targeted policies to enhance affordability, availability, and convenience of nutritious plant-based foods
The first BILGENSA Research Network workshop in Zambia: identifying research priorities, challenges and needs in genital bilharzia in Southern Africa
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Female genital schistosomiasis (FGS) and male genital schistosomiasis (MGS) are gender-specific manifestations of urogenital schistosomiasis. Morbidity is a consequence of prolonged inflammation in the human genital tract caused by the entrapped eggs of the waterborne parasite,
Schistosoma (S.) haematobium.
Both diseases affect the sexual and reproductive health (SRH) of millions of people globally, especially in sub-Sahara Africa (SSA). Awareness and knowledge of these diseases is largely absent among affected communities and healthcare workers in endemic countries. Accurate burden of FGS and MGS disease estimates, single and combined, are absent, mostly due to lack of awareness of both diseases and absence of standardized methods for individual or population-based screening and diagnosis. In addition, there are disparities in country-specific FGS and MGS knowledge, research and implementation approaches, and diagnosis and treatment. There are currently no WHO guidelines to inform practice. The BILGENSA (Genital Bilharzia in Southern Africa) Research Network aimed to create a collaborative multidisciplinary network to advance clinical research of FGS and MGS across Southern African endemic countries. The workshop was held in Lusaka, Zambia over two days in November 2022. Over 150 researchers and stakeholders from different schistosomiasis endemic settings attended. Attendees identified challenges and research priorities around FGS and MGS from their respective countries. Key research themes identified across settings included: 1) To increase the knowledge about the local burden of FGS and MGS; 2) To raise awareness among local communities and healthcare workers; 3) To develop effective and scalable guidelines for disease diagnosis and management; 4) To understand the effect of treatment interventions on disease progression, and 5) To integrate FGS and MGS within other existing sexual and reproductive health (SRH) services. In its first meeting, the BILGENSA Network set forth a common research agenda across
S. haematobium endemic
countries for the control of FGS and MGS.
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