Estimates Of Burden Research Articles

Machine learning-driven estimation of mutational burden highlights DNAH5 as a prognostic marker in colorectal cancer.

Tumor Mutational Burden (TMB) have emerged as pivotal predictive biomarkers in determining prognosis and response to immunotherapy in colorectal cancer (CRC) patients. While Whole Exome Sequencing (WES) stands as the gold standard for TMB assessment, carry substantial costs and demand considerable time commitments. Additionally, the heterogeneity among high-TMB patients remains poorly characterized. We employed eight advanced machine learning algorithms to develop gene-panel-based models for TMB estimation. To rigorously compare and validate these TMB estimation models, four external cohorts, involving 1,956 patients, were used. Furthermore, we computed the Pearson correlation coefficient between the estimated TMB and tumor neoantigen levels to elucidate their association. CD8+ tumor-infiltrating lymphocyte (TIL) density was assessed via immunohistochemistry. The TMB estimation model based on the Lasso algorithm, incorporating 20 genes, exhibiting satisfactory performance across multiple independent cohorts (R2 ≥ 0.859). This 20-gene TMB model proved to be an independent prognostic indicator for the progression-free survival (PFS) of CRC patients (p = 0.001). DNAH5 mutations were associated with a more favorable prognosis in high-TMB CRC patients, and correlated strongly with tumor neoantigen levels and CD8+ TIL density. The 20-gene model offers a cost-efficient approach to precisely estimating TMB, providing prognosis in patients with CRC. Incorporating DNAH5 within this model further refines the categorization of patients with elevated TMB. Utilizing the 20-gene model facilitates the stratification of patients with CRC, enabling more precise treatment planning.

Abstract B064: Prevalence and clinical relevance of clonal hematopoiesis in metastatic urologic malignancies

Abstract Introduction: Clonal hematopoiesis (CH) is an age-related process whereby hematopoietic progenitor cells with specific mutations gain a proliferative advantage, resulting in populations that can be detected in blood. CH is a major confounder in plasma cell-free DNA (cfDNA) assays that do not profile patient-matched white blood cell (WBC) DNA to distinguish circulating tumor DNA (ctDNA) somatic mutations from those with hematopoietic origin. We aimed to characterize CH in patients with advanced urologic cancers and clarify the potential for CH to interfere with plasma-based tumor genotyping. Methods: We applied error-corrected targeted DNA sequencing (median 2200X) to matched cfDNA and WBC DNA from 301 patients with advanced urothelial cancer (UC) or renal cell carcinoma (RCC) enrolled in a provincial biobank, using a 57 gene panel capturing key CH and urologic cancer genes. CH mutations were defined as those detected in both WBC and cfDNA with a variant allele frequency (VAF) exceeding a 0.25% limit of detection and supported by at least 5 mutant reads. In contrast, ctDNA mutations were required to be exclusively detected in plasma, with a cfDNA VAF ≥5 times the VAF in WBC. Results: 73% (221/301) of patients had ≥1 CH mutation with a VAF above 0.25% (35% of patients had a variant above 2% VAF), and CH- patients were younger than CH+ (RCC: 56 vs 68.5, p<0.01; UC: 63 vs 72, p<0.01). There was no difference in CH prevalence by biological sex. There was no difference in overall survival according to CH status (UC: [CH+] 13 vs [CH-] 16 months, p=0.98; RCC: [CH+] 33 vs [CH-] 49 months, p=0.77), in contrast to the presence of ctDNA mutations which is an established prognostic factor linked with shorter overall survival (UC: [ctDNA+] 10 vs [ctDNA-] 23 months, p<0.01; RCC: [ctDNA+] 15 vs [ctDNA-] 49 months, p<0.01). CH+ patients carried CH mutations most commonly within hematologic malignancy-associated genes (e.g. DNMT3A [58%] and TET2 [26%]), although genes linked to DNA damage response such as TP53 (10%) and ATM (9%) were also mutated. PPM1D was mutated more frequently in UC compared to RCC within CH+ patients (UC: 22%, RCC: 9%, p<0.01), likely attributable to platinum chemotherapy exposure prior to blood collection in 50% of the UC cohort. Importantly, a notable proportion of mutations in UC- or RCC-relevant driver genes originated from CH rather than cancer, including 28% and 65% of mutations falling in TP53 and ATM, respectively. Finally, randomly downsampling sequencing reads from WBC DNA suggested that 500X coverage is sufficient to resolve 90% of CH events with >1% VAF. Conclusion: CH was highly prevalent in patients with advanced urologic malignancies but had no impact on survival in this heterogeneous real-world cohort. CH commonly affected clinically-relevant driver genes that are also altered in solid cancers, potentially causing false-positive genotyping and inflating tumor mutation burden estimates in plasma-only ctDNA assays. Incorporating WBC sequencing to liquid biopsy assays can help correctly identify tumor-originating mutations. Citation Format: Aslı D Munzur, Jack V W Bacon, Francine Fishbein, Gráinne Donnellan, Cecily Q Bernales, Karan Parekh, Gillian Vandekerkhove, David C Müller, Cameron Herberts, Lucia Nappi, Corinne Maurice-Dror, Kim N Chi, Bernhard J Eigl, Christian Kollmannsberger, Maryam Soleimani, Alexander W Wyatt. Prevalence and clinical relevance of clonal hematopoiesis in metastatic urologic malignancies [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B064.

Abstract B009: Individualized-tumor-informed panel approach enables ultra-sensitive ctDNA-based minimal residue disease monitoring for high-risk pediatric cancers

Abstract While the use of ctDNA-based minimal residual disease (MRD) monitoring is gaining popularity in adult cancers, this approach is not yet widely adopted in pediatric cancers (PCs). We developed a robust and sensitive assay to monitor ctDNA in PCs, which overcomes PC-specific challenges including low tumor mutational burden, paucity of hotspot mutations and low blood volume. To address these challenges, our innovations include personalized panel design that targets primary tumor mutations from each patient, a fixed panel targeting hotspot mutations, error suppression from duplex deep sequencing and customized pipeline for tumor burden estimation. We retrospectively analyzed 661 blood or cerebrospinal fluid (CSF) samples from 168 patients. We achieved an average detection limit of 0.005% ctDNA purity leading to MRD detected ranging from 0.001% to 100% with brain tumor consistently showing a low MRD. At disease diagnosis, progression and relapse, our assay identified ctDNA in over 93% of extra- cranial solid tumors, 90% of leukemia, 89% of sarcoma, and 90% of neuroblastoma. For brain tumors, we detected MRD in ∼90% of CSF samples, and in ∼60% of blood samples, a major advance over previous approaches. Importantly, we detected MRD in ∼ 20% of cases with a clinically complete response, predicting relapse up to 6 months before clinical confirmation. Overall, these results demonstrate that our monitoring assay for PCs is an important addition to standard of care for precision-guided treatment. Citation Format: Rob Salomon, Wenhan Chen, Charles Shale, Mojgan Toumari, Aileen Lowe, Wenyan Li, Jingwei Chen, Sajad Razavi-Bazaz, Paulette Barahona, Louise Cui, Chelsea Mayoh, Sam El-Kamand, Vanessa Tyrrell, Marie Wong-Erasmus, Loretta MS Lau, Noemi Fuentes-Bolanos, Edwin Cuppen, Dong-Anh Khoung-Quang, Jordan Staunton, Marion K Mateos, Toby Trahair, Michelle Haber, David S Ziegler, Paul Ekert, Peter Priestley, Mark Cowley. Individualized-tumor-informed panel approach enables ultra-sensitive ctDNA-based minimal residue disease monitoring for high-risk pediatric cancers [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B009.

Abstract 4123373: Estimating obesity-attributable cardiovascular disease burden in the United States: a Bayesian network analysis

Background: Obesity is a known contributor to the development of cardiovascular disease (CVD) and increases the risk of subsequent mortality. To fully understand the burden of obesity, accurate information regarding its effects on CVD is necessary. Current estimates are limited by a focus on direct effects, use of non-representative data sources, and a reliance on inaccurate diagnosis codes. Aim: To determine the size of CVD burden attributable to obesity in the US and identify the mechanisms through which obesity affects CVD. Methods: This study used data collected from US adults (aged ≥35 years) participating in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020 and US Census projections. NHANES data were longitudinally adapted, and participants were excluded if they had missing data for weight history, risk factors, or a given outcome of interest. Bayesian networks (BNs) mapping out the relationship between risk factors and each outcome were constructed to estimate current CVD risk and expected CVD risk in the absence of obesity. Obesity-attributable CVD burden was then calculated for each outcome, and the direct and indirect pathways through which changes in CVD risk occur were characterized. A subgroup analysis was conducted in non-smoking participants aged ≤65 years for whom obesity is likely the primary CVD risk factor. Results: The final sample included data from approximately 29,000 participants. Of these, 1286 (4.3%) had a history of myocardial infarction (MI), 1283 (4.4%) had a history of stroke, 1092 (3.7%) had a history of heart failure (HF), and 1992 (6.7%) had a history of CVD (composite of MI, stroke, angina, coronary heart disease, and HF). Results from the fitted BN indicate that 21% of MI, 16% of stroke, 38% of HF, and 19% of CVD cases were attributable to obesity, with ≥80% of this burden due to the effect of obesity on intermediate risk factors (hypertension, type 2 diabetes, and prior cardiovascular events). In the subgroup analysis, the obesity-attributable CVD burden was approximately twice as high for non-smokers aged ≤65 years, with 39% of MI, 32% of stroke, 65% of HF, and 38% of CVD cases attributable to obesity. Conclusion: Through a sophisticated network modeling approach, we generated estimates of obesity-attributable CVD burden in the US. Results highlight the importance of obesity as a CVD risk factor, particularly in younger non-smokers, and provide insight into the nature of this relationship.

An automated pheochromocytoma and paraganglioma lesion segmentation AI-model at whole-body 68Ga- DOTATATE PET/CT.

Somatostatin receptor (SSR) targeting radiotracer 68Ga-DOTATATE is used for Positron Emission Tomography (PET)/Computed Tomography (CT) imaging to assess patients with Pheochromocytoma and paraganglioma (PPGL), rare types of Neuroendocrine tumor (NET) which can metastasize thereby becoming difficult to quantify. The goal of this study is to develop an artificial intelligence (AI) model for automated lesion segmentation on whole-body 3D DOTATATE-PET/CT and to automate the tumor burden calculation. 132 68Ga-DOTATATE PET/CT scans from 38 patients with metastatic and inoperable PPGL, were split into 70, and 62 scans, from 20, and 18 patients for training, and test sets, respectively. The training set was further divided into patient-stratified 5 folds for cross-validation. 3D-full resolution nnUNet configuration was trained with 5-fold cross-validation. The model's detection performance was evaluated at both scan and lesion levels for the PPGL test set and two other clinical cohorts with NET (n = 9) and olfactory neuroblastoma (ONB, n = 5). Additionally, quantitative statistical analysis of PET parameters including SUVmax, total lesion uptake (TLU), and total tumor volume (TTV), was conducted. The nnUNet AI model achieved an average 5-fold validation dice similarity coefficient of 0.84 at the scan level. The model achieved dice similarity coefficients (DSC) of 0.88, 0.6, and 0.67 at the scan level, the sensitivity of 86%, 61.13%, and 61.64%, and a positive predictive value of 89%, 74%, and 86.54% at the lesion level for the PPGL test, NET and ONB cohorts, respectively. For PPGL cohorts, smaller lesions with low uptake were missed by the AI model (p < 0.001). Anatomical region-based failure analysis showed most of the false negative and false positive lesions within the liver for all the cohorts, mainly due to the high physiologic liver background activity and image noise on 68Ga- DOTATATE PET scans. The developed deep learning-based AI model showed reliable performance for automated segmentation of metastatic PPGL lesions on whole-body 68Ga-DOTATATE-PET/CT images, which may be beneficial for tumor burden estimation for objective evaluation during therapy follow-up. https://www. gov/study/NCT03206060 , https://www. gov/study/NCT04086485 , https://www. gov/study/NCT05012098 .

The global burden of enteric fever, 2017–2021: a systematic analysis from the global burden of disease study 2021

Enteric fever is a major public health challenge in developing countries. We conducted a systematic analysis from the Global Burden of Diseases 2021 Study to provide updated estimates of enteric fever's burden. We presented estimates for incident cases and deaths, age-standardized incidence and mortality rates, years of life lost (YLLs), and case-fatality rates spanning the study period of 2017-2021, stratified by region, country, socio-demographic index (SDI), and age group. Random-effects Poisson regression for longitudinal data was used to estimate the association between SDI and case-fatality rates, adjusting for antimicrobial resistance patterns. In 2021, there were 9.3 million global cases of enteric fever (95% uncertainty interval: 7.3-11.9) and 107.5 thousand deaths (56.1-180.8). The age-standardized incidence rate decreased from 152/100,000 person-years (118-195) in 2017 to 128/100,000 person-years (100-163) in 2021, and the mortality rate decreased from 1.87/100,000 person-years (0.95-3.18) to 1.50/100,000 person-years (0.78-2.54). There were wide geographical differences, with South Asia contributing the most cases and deaths. Age-standardized incidence exceeded the threshold for "high burden" of enteric fever (100/100,000 person-years) in 23 countries in2021.Children under five accounted for 40% of deaths and 47% of YLLs, with incidence and mortality peaking during the second year. Case-fatality was highest in low SDI countries and showed a global trend toward reduction, except among children aged 1-4 years. After adjusting for the prevalence of multidrug resistance, fluoroquinolone non-susceptibility, and third-generation cephalosporin resistance, a higher SDI was associated with a lower case-fatality rate, with a 1.1% (0.7-1.7) reduction for each percentage point increase in SDI. Despite notable improvements, several countries still showed a high burden of enteric fever, which remains a significant global health concern, especially among children under five. Although enhancing water and sanitation systems is crucial, the most significant reductions in the global disease burden are likely to be achieved through broader vaccine coverage. This includes the use of typhoid conjugate vaccines, which are effective in infants and young children and offer extended protection, along with improved data collection and surveillance to guide vaccine distribution efforts across high-incidence areas. This work was partially supported by "Ricerca Corrente" funding from Italian Ministry of Health to IRCCSHumanitas Research Hospital.

Burden of Ischemic Heart Diseases among US States from 1990-2019.

Ischemic Heart Disease (IHD) is a leading cause of global mortality, including in the United States. Understanding the burden of IHD in the United States is crucial for informed decision-making and targeted interventions aimed at reducing morbidity and mortality associated with this leading cause of death. This study aimed to understand the burden of IHD, identify gender disparities and risk factors, explore the relationship between socioeconomic growth and IHD, and analyze risk factor distribution across the states of the United States. This study utilized data from the Global Burden of Diseases Study 2019, which provided comprehensive information on IHD from 1990 to 2019. Data related to IHD from these years were extracted using a query tool from the Institute for Health Metrics and Evaluation (IHME) website. The study assessed the relationship between IHD and socioeconomic development using the Socio-demographic Index (SDI) and measured the overall impact of IHD using Disability-adjusted Life Years (DALYs), considering premature death and disability. Additionally, the study analyzed the burden of IHD attributed to six main risk factors. Data analysis involved comparing prevalence, mortality, SDI, DALYs, attributable burden, and risk estimation among the states. Between 1990 and 2019, there was an improvement in socioeconomic development in all states. Age-standardized rates of disease burden for IHD decreased by 50% [ASDR 3278.3 to 1629.4 (95% UI: 1539.9-1712.3) per 100,000] with the most significant decline observed in Minnesota. Males had higher burden rates than females in all states, and the southeast region had the highest mortality rates. The prevalence of IHD showed a declining trend, with approximately 8.9 million cases (95% UI: 8.0 million to 9.8 million) in 2019, representing a 37.1% decrease in the Age-standardized Prevalence Rate (ASPR) from 1990. Metabolic risks were the leading contributors to the disease burden, accounting for 50% of cases, with Mississippi having the highest attributable risk. Arkansas had the highest attributable risk for high cholesterol and smoking. Conversely, Minnesota had the lowest burden of IHD among all the states. This study highlights variations in the burden of IHD across US states and emphasizes the need for tailored prevention programs to address specific risk factors and gender differences. Understanding the trend in IHD may inform policymakers and healthcare professionals in effectively allocating resources to reduce the burden of IHD and improve national health outcomes.

Spectrum and Antifungal Drug Resistance among Fungal Pathogens Isolated from Prison Inmates in Nairobi, Kenya

Background The emergence of antifungal resistance in fungal pathogens highlights the need for local epidemiological data to guide empirical therapy in clinical settings. Fungal research and anti-fungal drug resistance studies are limited in developing countries; hence, there is a need for burden estimation in low- and middle-income countries. This study aimed to determine the spectrum of fungal pathogens and the anti-fungal resistance profile of fungal pathogens isolated from the respiratory and urinary tracts of prison inmates in Nairobi, Kenya. Methods A cross-sectional study was conducted in which sputum and urine samples were obtained from inmates presenting with symptoms of respiratory and urogenital infections at a prison outpatient clinic. One hundred and sixty-two samples were collected and subjected to fungal investigation using standard protocols. Susceptibility to fluconazole, itraconazole, and voriconazole was assessed using standard broth microdilution. Clinical and sociodemographic data were obtained using a structured questionnaire. Results From the 162, 94 samples were positive for fungal pathogens, with an overall prevalence of 58%. Seventeen (18%) of the isolated fungi were Aspergillus fumigatus, Aspergillus flavus and Histoplasma. There was a statistically significant difference between fungal pathogens isolated from the respiratory and urogenital tracts in both sexes (p&lt;0.05). Antifungal susceptibility testing against itraconazole showed 2 of Aspergillus flavus and Aspergillus fumigatus were resistant. Conclusion Mycological agents are significant causes of respiratory and UTI infections among prison inmates, which could be attributed to prison conditions and misdiagnosis as bacterial infections. This highlights the need for specific control measures to reduce exposure to fungal infections in prisons and in the general population.

Health consequences of harmful chemicals in foods: insights from the WHO Global Burden of Foodborne Disease Study

Abstract Foods can be an important source of human exposure to harmful chemicals. Contamination can occur at any stage of the food chain; with chemicals that occur naturally or by anthropogenic pollution in the environment and during production processes from farm level to the kitchen of the consumer. The variety of chemicals in foods is broad and associated with a wide range of adverse health effects. Where toxicological risk assessment of chemicals in foods serves the purpose of protecting populations from exposure levels constituting a health concern, burden of disease methodology provides a quantitative snapshot of the current impact of chemicals on disease occurrence and population health. This allows for the comparison across hazards, health effects and foods and eventually prioritized allocation of resources to maximize health benefits. Following the advice by the World Health Organization Foodborne Disease Burden Epidemiology Reference group (WHO/FERG), WHO published in 2015 the first estimates of the global burden of foodborne disease. More than 400,000 deaths and 33 million disability-adjusted life years were estimated due to unsafe foods in 2010; the largest proportion due to foodborne pathogens, as the contribution of only 3 chemical hazards (dioxins, aflatoxin B1 and cassava cyanide) was included. WHO, once more under the advice by the re-established WHO/FERG (2021-2025), is currently working to update the 2010 estimates. Besides applying updated data and methodological improvements in managing data gaps and time series analysis, WHO’s ambition is to consider a wider range of chemicals and associated health effects for the year of 2020. In this presentation, we will share insights on the WHO estimates of the global burden of foodborne chemicals, and explore the methodological opportunities and challenges that estimating the burden of foodborne chemicals provides for informing policies.

Working on new topics: Estimation of the burden of zoonotic diseases

Abstract Zoonoses, diseases naturally transmitted between vertebrates and humans, represent significant global health threats. These diseases not only affect human health but also impose a considerable burden on animal populations, emphasizing the need for a One Health approach that integrates strategies across human, animal, and environmental health sectors. The socioeconomic impacts of zoonoses are profound in low- and middle-income countries, disrupting production systems, impacting livelihoods, and compromising food security. Populations in these regions are excessively affected, highlighting the urgent need for a comprehensive approach. The disability-adjusted life year (DALY) quantifies disease burden in terms of morbidity and mortality. The zoonotic DALY (zDALY) expands this metric by incorporating the burden on animals through the ‘animal loss equivalents’, accounting for both fatal and non-fatal outcomes in livestock. However, zDALYs do not encompass broader economic impacts associated with prevention and treatment. Cost of illness (COI) studies further quantify the financial costs due to health issues; ad hoc approaches can be used to quantify other costs related to animal disease control and eradication, trade and movement Implications, or loss of consumer confidence. While few zoonoses, such as cystic echinococcosis and brucellosis, have comprehensive data across these metrics, most do not. While these metrics provide complementary insights, no holistic metric currently encompasses all necessary aspects to fully assess the burden of zoonoses within a One Health framework. This presentation aims to offer state-of-the-art estimates of the disease burdens of zoonoses, employing DALY, zDALY, and COI studies. It will explore how to integrate these metrics from a One Health perspective. Indeed, only by integrating health and economic metrics that consider the well-being of humans and animals, can the One Health approach effectively be developed for zoonotic diseases.

Burden of inflammatory bowel disease in Belgium, 2020

Abstract Inflammatory bowel disease (IBD) comprises digestive disorders resulting from non-infectious inflammation of the colon and gastrointestinal tract. With its global prevalence on the rise, IBD poses significant challenges to healthcare systems. There is a need for more accurate disease burden estimates to guide decision-making processes within the health sector. As a part of the Belgian national burden of disease study (BeBOD), this study aims to estimate the burden of IBD in Belgium based on locally available data. We estimated the Belgian IBD burden in 2020 in terms of mortality, prevalence, years of life lost (YLLs) due to premature death, years lived with disability (YLDs), and disability-adjusted life years (DALYs). As there is no single comprehensive data source on prevalence of IBD in Belgium, a critical appraisal of existing local and national data sources was conducted. Prevalence data were combined with disability weights to yield YLDs. YLLs were calculated using the most recent Global Burden of Disease (GBD) 2019 reference life table and the number of deaths caused by non-infective IBD (ICD-10 K50-52). Cause of death data were extracted from Statbel, the Belgian statistical office. The best available data source to estimate the IBD prevalence in Belgium was a widespread network of general practitioners. The prevalence of IBD was 1.5% in 2020. The prevalence-based YLD for IBD was 220 YLDs per 100 000, while the YLL rate was 11.5 per 100 000. We estimated 26 276 DALYs caused by IBD in 2020. Of the total DALYs caused by IBD, 5% were due to YLLs and 95% were due to YLDs. Our burden estimates for IBD in Belgium were however higher than those of the GBD study. IBD imposes a low fatal burden, whereas the burden of morbidity is more prominent. Our findings could be useful for policy makers to justify and prioritize resource allocation. Integrating the current research in BeBOD will allow monitoring the burden of IBD over time. Key messages • Inflammatory bowel disease is characterized by a substantial non-fatal burden due to chronic relapsing and persistent symptoms. • National inflammatory bowel disease burden estimates are useful to guide decision-making within the health sector.

Burden of disease due to road traffic noise in Flanders, Belgium

Abstract This study estimates the disease burden of ischemic heart disease (IHD), stroke and diabetes mellitus attributable to road traffic noise in the Flemish Region (Belgium) for the year 2020, expressed in disability-adjusted life years (DALYs). The research proposes an approach to stratify population exposure to noise according to age and sex, which allows to examine internal differences in noise burden related to both varying risk and baseline burden. Stratification of population exposure to noise is achieved by (1) linking modelled noise exposure to age- and sex-stratified population data at small area-level, (2) dividing the prevalence in each exposure class proportionally over the strata, and (3) aggregating the small areas to a Flemish total per stratum. Annual day-evening-night level exposure is translated into the fraction of attributable burden relying on relative risks (RR) from the WHO’s Environmental Noise Guidelines and more recent studies. Baseline burden for the three outcomes is sourced from the Belgian National Burden of Disease Study. The lower and upper bound of the RR’s 95% confidence interval (CI) are used to calculate the uncertainty range on the burden estimates. The total noise DALYs estimated are 1092 (95% CI: 135, 2061) for IHD, 761 (379, 1017) for stroke, and 671 (486, 918) for diabetes. Noise burden rates rise steeply with age for all outcomes, although the wide CIs on the IHD estimates prevent to ascertain a significant trend. The IHD burden is twice as high in men as in women, while both sexes are almost equal for the other outcomes. The variations between age and sex groups are largely explained by differences in baseline burden, as exposure is fairly constant across strata. This study estimates age- and sex-stratified disease burden attributable to noise traffic in Flanders, Belgium. As differential exposure between the population subgroups is limited, any variation in noise DALYs is mainly related to stratum-specific baseline burden. Key messages • Road traffic noise is responsible for hundreds of healthy life years lost in Flanders, Belgium. • The noise burden for stroke and diabetes rises sharply with age, and the burden for ischemic heart disease is twice as high in men as in women.

The burden of psoriasis in Belgium, 2021

Abstract Psoriasis is a common, chronic, inflammatory skin disease with a great impact on healthcare systems. Given the limitations of the currently available burden estimates, estimates of the Belgian national burden of disease study are necessary in order to guide decision-making processes within the health sector. According to the Global Psoriasis Atlas, the prevalence of psoriasis is rising globally. The current study aims to estimate the burden of psoriasis in Belgium using national data. As there is no single comprehensive data source on prevalence of psoriasis in Belgium, a critical appraisal of existing local and national data sources was conducted. We estimated the non-fatal psoriasis burden in terms of years lived with disability (YLD). Estimated prevalence data were combined with disability weights to yield YLDs imposed by psoriasis. Mortality attributable to psoriasis was assumed to be zero, in line with the Global Burden of Disease study (GBD) 2019. We assessed three data sources containing information on existing cases with psoriasis in Belgium. Based on qualitative and quantitative appraisal, a widespread network of general practitioners was identified as the best available national data source. In 2021, the prevalence of psoriasis in Belgium was 2.1%, leading to 13084 DALYs (113 DALYs per 100 000). The burden of psoriasis was in line with national disease burden estimates for bipolar disorder, multiple myeloma, and hearing loss. Our prevalence, YLD, and DALY estimates for psoriasis in Belgium were however lower than those of the GBD study. Psoriasis imposes a non-negligible burden on population health in Belgium, despite it not being a cause of death. Along progression in psoriasis management, objective evaluation of psoriasis burden is critical to track the trends at the population level. Key messages • Psoriasis is a common skin disease with a relatively high morbidity burden. • Information on psoriasis prevalence and burden are crucial for disease management and appropriate health-care planning.

Past-year mental health issues: discrepant survey &amp; administrative data

Abstract Introduction Accurately measuring mental health disorder prevalence is crucial for public health planning. Administrative and survey data are common methods, but often yield differing results. This study compares case identification of mental health issues across these data sources in Slovenia. Methods We linked the 2019 European Health Interview Survey (EHIS) with three Slovenian health administrative databases: the National Hospital Health Care Statistics Database, Outpatient Prescription Drugs Database, and Absence From Work Database. Case identification utilized self-report of any mental health issue in the past 12 months and healthcare utilization records in 12 months preceding participation in EHIS. Multinomial logistic regression was used to examine the association between socio-demographic factors and case identification across data sources. Results Significant differences were found in 12 month prevalence of any mental health issue estimates between data sources. Only 45.9% of self-reported cases were identified in administrative data, and 36.6% of administrative cases self-reported mental health issues (Kappa = 0.302). Socio-demographics, including age, gender, education, and employment status, were significantly associated with the likelihood of identification in specific data sources. Discussion Our findings underscore the importance of data source and assessment tool selection on mental health prevalence estimates. Variations in identification across population subgroups could reflect differences in healthcare access and self-disclosure biases. Linking data sources and considering their inherent limitations is crucial for accurate burden estimation. Key messages • Data source and assessment methods significantly impact how we identify individuals with mental health issues in the past year. • Combining data sources and understanding their limitations is essential for improving mental health burden estimation.

Estimation of Environmental Burden of Disease related to Arsenic exposure in European Populations

Abstract Background Arsenic (As) exposure poses significant health risks to exposed populations, with exposure occurring predominantly via diet for the general population as recently referred by the European Food Safety Authority. This study assesses the environmental burden of disease (EBD) for three cancer types related to arsenic, across Europe. Methods A literature review was conducted to 1) identify the dose-response function (DRF) to assess the cancer risk in European populations, and 2) define EBD approaches applicable to the available data. Country-specific data (Belgium, Denmark, Portugal) for EBD calculation (exposure, socioeconomic status, health outcomes) were gathered. Disability-Adjusted Life Years (DALY) estimations were performed by calculating attributable cases (AC). Results Two main references are used for DRF: the United States Food and Drug Administration DRF for assessing bladder and lung cancer risks, and the United States Environmental Protection Agency DRF for skin cancer. Preliminary results for Belgium indicate that inorganic arsenic dietary exposure ranges from 0.084 [0.080 - 0.088] to 0.102 [0.097 - 0.107] µg/kg body weight per day, varying with education level. Stratified estimates suggest that individuals with higher educational attainment (ISCED levels 5 &amp; 6) have a marginally higher average daily intake of arsenic compared to those with lower educational attainment (ISCED levels 0, 1 &amp; 2). DALY attributable to inorganic arsenic exposure follow the same trend as exposure levels, i.e. individuals with a higher education level bear a higher burden of disease than individuals of the low education stratum. This concerns the three studied cancers. Conclusions This study quantifies DALY related to inorganic arsenic from dietary exposure for different European countries. Our findings will contribute to better target public health policies and interventions for arsenic risk mitigation. Key messages • Exposure to inorganic arsenic is confirmed in European countries. • EBD studies guide action priorities to tackle chemical risk factors.

Developing survey instruments for low back and neck pain to improve disease severity estimates for burden of disease assessment

Abstract Two people living with the same disease can have very different experiences; one has little consequence, whilst the other struggles with much more debilitating consequences that impacts how they live their lives day-to-day. A growing body of research highlights the need for better estimates of disease severity to facilitate better estimation of the non-fatal burden of disease (BOD). Routine data does not always offer solutions because it’s often not coded at a granular enough level to map to individual health states. Data offering solutions are scarce and therefore not available across time or space. Most commentators have quantified the problem of assuming the same proportional severity splits to fill data gaps; a problem common to the Global Burden of Disease (GBD) study and independent BOD studies. However, whilst the need for highlighting the problems associated with this assumption remains, there are other positive steps that can be taken to overcome it. We propose how reproducible approaches can be developed, and present how they can be used to develop disease severity estimates. This involves developing a survey instrument to estimate the overall and health state prevalence of back pain and neck pain, basing health state definitions from the GBD non-fatal disease models, where the classification of cases by severity is based on the combination of respondent’s answers. Furthermore, we discuss how self-assessed severity estimates allow for internal validity checks, but also more widely offer opportunities to appraise the appropriateness of GBD non-fatal disease models. The development, and publication, of survey instruments can assist both independent studies and the GBD study to improve estimates of disease severity, as well as retaining important opportunities for cross-country comparability. Understanding the spectrum of severity is important for understanding how disease impacts populations and can inform healthcare provision and expenditure strategies.

Economic burden of suicide in Sweden in 2022

Abstract Background Suicide and suicidal behaviors bring massive human, social and economic impacts. Estimates of the cost of suicide can give some guidance as to where research on developing new interventions might be focused to give the greatest potential gain. The aim of the study is to quantify the economic cost of suicide in Sweden in 2022. Methods Incidence of suicide attempts and mortality due to suicide, intentional and undetermined (ICD10 X60-X84 and Y10-Y34) were sourced from the Swedish National Board of Health and Welfare databases for 2022. Cost were estimated from a societal perspective, including costs for inpatient and outpatient care, medication, police and justice activities as well as productivity losses due to early mortality. Results In 2022, a total of 1,569 suicide death were registered in Sweden (1,102 men and 467 women). The incidence rate remains stable during the last ten years, 17 death per 100 000. In total, 18,854 patients (10, 359 women and 8,459 men) were treated in inpatient and outpatient hospital care with suicide-related diagnoses, generated 32,843 days in inpatient care and 11,471 outpatient care visits. Direct costs for suicide death including forensic examination, emergency services, police investigation and property damage were estimated as €6,02 million, while indirect costs for productivity losses totaled €690 million. Direct healthcare costs for suicide related treatment were estimated at €54.3 million. Overall, suicide and suicide attempts cost around €750 million per year to society. Conclusions Estimates of the economic burden of suicide are needed for the Swedish setting, and these amounted to €60.3 million in direct costs and €690 million in indirect costs in 2022. The cost might be underestimated because the societal cost of suicide bereaved persons was not considered. These cost estimates can provide useful inputs to a cost-effectiveness analysis of a specific preventive intervention, and to its subsequent evaluation. Key messages • Economic burden of suicide is substantial for society. • Public health policies aimed at the prevention of suicide should be increased.

Environmental burden of disease related to pyrethroid-insecticide exposure and neurodevelopmental toxicity in Europe based on human biomonitoring

Abstract As indicated by human biomonitoring (HBM) studies, exposure to pyrethroids is widespread in Europe with significantly higher exposure observed in children compared to adults. Epidemiological, toxicological, and mechanistic studies raise concerns about potential health effects in humans and, particularly, behavioral disorders such as attention deficit hyperactivity disorder (ADHD) in children at low levels of exposure. Based on an exposure-response function from a single European study and on available quality-assured and harmonized HBM data collected in France, Germany, Iceland, Switzerland, and Israel, an initial estimate of the environmental burden of disease for ADHD associated with pyrethroid exposure (measured by the metabolite 3-phenoxybenzoic acid) was made for individuals aged 0-19 years. The estimated yearly number of prevalence-based disability-adjusted life years (DALYs) per million inhabitants due to ADHD were 34 DALYs for Israel, 26 DALYs for France, 14 DALYs for both Switzerland and Iceland, and 4 DALYs for Germany. Additionally, a substantial number of ADHD cases, averaging 18%, were associated with pyrethroid exposure. Yet, these figures should be interpreted with caution given the uncertainty of some input parameter. In addition to burden of disease estimates due to ADHD, the associated burden of autism-spectrum disorder (ASD) due to pyrethroid exposure and the health economic costs attributable to ADHD and ASD will also be investigated further. To ensure adequate follow-up of policy measures and more robust disease burden estimates, more HBM studies are recommended, along with increased efforts to harmonize the design of epidemiological studies to ensure more meaningful meta-analyses of exposure-response functions. This is particularly important for pyrethroids as more evidence on potential adverse health effects is continuously emerging.

Long-term ozone exposure and asthma: a systematic review and meta-analysis

Abstract Background Ambient air pollution, particularly surface ozone, is a significant global health concern, with 9 out of 10 people exposed to levels exceeding WHO guidelines. This exposure is linked to approximately 7 million premature deaths annually, a number expected to double by 2050. While the effects of short-term exposure to ozone on exacerbation of asthma symptoms and mortality are well-documented, the impact of long-term exposure remains unclear. Aim This systematic literature review aims to quantify the association between long-term exposure to ozone and asthma incidence and prevalence and derive an exposure-response relationship. Methods International electronic databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science, were searched, supplemented by grey literature sources such as Google Scholar and WHO - Global Index Medicus from conception to July 31, 2023. Observational epidemiological cohort, case-control, or cross-sectional studies reporting quantitative associations between exposure and outcome were included. Meta-analysis will synthesize effect size estimates using a Meta-Regression - Bayesian, Ensemble, Regularized, Trimmed (MR-BRT) model. Results A total of 5,947 titles were initially identified from databases, and following the removal of duplicates, 3,235 titles and abstracts were screened, resulting in 84 articles deemed eligible for full-text review. The full-text screening identified 29 studies comprising 38 articles. A comprehensive overview of the included studies will be provided. We will describe the study settings, design, and measurement methods used by the identified studies. Furthermore, results of the MR-BRT model will be summarized, and exposure-response functions will be discussed. Funding: This work is part of the BEST-COST project which is funded by the European Union’s Horizon Europe programme under Grant Agreement No.101095408. Key messages • This research fills the gap in understanding the association between long-term exposure to ambient ozone and asthma incidence and prevalence. • Developing exposure-response functions would enable estimation of the disease burden associated with long-term ozone exposure.

Establishing disease models for the Belgian national burden of disease study: challenges and perspectives

Abstract The Belgian national burden of disease study (BeBOD) was launched in 2022, and currently provides disease burden estimates for 38 key diseases. The calculation of the non-fatal component of the disease burden, the Years Lived with Disability (YLD), follows a stepwise approach that aims to establish priority outcomes; quantify prevalence “best estimates”; establish disease models; and perform expert evaluation of methods and results. The disease models visualize the relationship between the different health states associated with a given outcome. Health states include the different acute and chronic stages of the outcome (including complications), which may be stratified in different severity levels (e.g., mild, moderate, severe). Disease models used in burden of disease studies primarily aim to document the considered health states, and do not aim at a representation of the complete clinical picture of the condition. The disease models instead help in understanding how the number of cases for each health state is calculated. Models typically start with one “parent node”, which contains all cases. This parent node then gives rise to multiple “child nodes”, with the terminal child nodes representing the individual health states. In BeBOD, disease models and severity distributions are adapted from the Global Burden of Disease (GBD) study, and complemented with local data where possible. This process ensures consistency with available disability weights, while still allowing for local data to feed into the calculations. In this presentation, we will demonstrate the BeBOD process for establishing disease models based on a number of archetypical examples, which represent varying challenges linked to disease model complexity, clarity and completeness of the GBD disease model documentation, and availability of local data. Future perspectives will be discussed, including the improved leveraging of local clinical data, and the implementation of tailored active data collection.