Annual Mortality Research Articles

Was Palaeolake Messel a death-trap? Insight from modern bat drownings and decay experiments

AbstractThe Messel Pit is an ancient maar lake that preserves an ecosystem from the last greenhouse phase of Earth’s climate with exceptional fidelity. There are two main competing hypotheses to explain the occurrence of animal fossils at Messel: asphyxiation in layers of heavy, toxic gases like carbon dioxide, and death following ingestion of surface water contaminated by cyanobacterial toxins. Both hypotheses imply mortality much higher than the null hypothesis of accidental death, for instance by drowning. We tested these hypotheses amongst bats by recourse to a unique survey on bats that drowned in modern swimming pools. We further conducted experiments on the fate of fresh bat carcasses that simulate drowning. Finally, we estimated the annual rate of bat fossil production at Messel. Overall, there are few good surveyed predictors of whether bats drown in swimming pools: most physical parameters like pool size or the height and distance of obstructions were not associated with mortality, although pool liner type would be a good candidate parameter for future study. In our experiments, carcasses with water-filled lungs tend to sink more quickly than those with air-filled lungs; all carcasses that initially sink “bloat and float” at shallow depths, but all floaters eventually disarticulate and sink within days to weeks. Our estimates of annual bat mortality at Palaeolake Messel are of the same order of magnitude as mortality in swimming pools. Mass mortality horizons for vertebrates are very rare at Messel. In sum, our quantitative analyses provide no evidence that bat mortality at Messel rises above background levels.

Integrating information from historical data into mechanistic models for influenza forecasting.

Seasonal influenza causes significant annual morbidity and mortality worldwide. In France, it is estimated that, on average, 2 million individuals consult their GP for influenza-like-illness (ILI) every year. Traditionally, mathematical models used for epidemic forecasting can either include parameters capturing the infection process (mechanistic or compartmental models) or rely on time series analysis approaches that do not make mechanistic assumptions (statistical or phenomenological models). While the latter make extensive use of past epidemic data, mechanistic models are usually independently initialized in each season. As a result, forecasts from such models can contain trajectories that are vastly different from past epidemics. We developed a mechanistic model that takes into account epidemic data from training seasons when producing forecasts. The parameters of the model are estimated via a first particle filter running on the observed data. A second particle filter is then used to produce forecasts compatible with epidemic trajectories from the training set. The model was calibrated and tested on 35 years' worth of surveillance data from the French Sentinelles Network, representing the weekly number of patients consulting for ILI over the period 1985-2019. Our results show that the new method improves upon standard mechanistic approaches. In particular, when retrospectively tested on the available data, our model provides increased accuracy for short-term forecasts (from one to four weeks into the future) and peak timing and intensity. Our new approach for epidemic forecasting allows the integration of key strengths of the statistical approach into the mechanistic modelling framework and represents an attempt to provide accurate forecasts by making full use of the rich surveillance dataset collected in France since 1985.

Trends in heart failure mortality in Sweden between 1997 and 2022.

Data from US have shown a reversal in the improvement of heart failure (HF)-related mortality over the last ~10 years. It is unknown whether these trends generalize to European universal healthcare systems. We assessed temporal trends in (i) HF-related mortality in the overall national population; and (ii) all-cause mortality following an incident HF diagnosis, overall and stratified by ejection fraction (EF), in Sweden between 1997 and 2022. Annual mortality rates with a HF diagnosis as underlying cause were extracted from the Cause of Death Register. All-cause mortality following incident HF was assessed in two HF cohorts derived from the National Patient Register (NPR) and the Swedish HF Registry (SwedeHF). Temporal trends were presented as average annual percentage change (AAPC). Between 1997 and 2022, age-adjusted HF-related mortality in the general population declined from 33.4 to 23.8 per 100 000 individuals (AAPC -2.15%, p < 0.001). In the HF cohort from NPR (n = 423 092), all-cause mortality at 1, 3, and 5 years following a first diagnosis of HF was 25%, 46%, and 58%, respectively, in 2022; 1-year mortality declined (AAPC -1.10%, p < 0.001) over time regardless of age or sex. In SwedeHF (n = 63 753), the decline in 1-year mortality was less steep with increasing EF (AAPC -2.64%, p < 0.001; -2.30%, p = 0.062; and -2.16%, p = 0.032 in EF <40%, 40-49%, and ≥50%, respectively). Heart failure-related mortality has declined over the last ~25 years in Sweden. All-cause mortality in patients with HF has also declined, more in HF with reduced than preserved EF, mirroring the different availability of life-saving treatments across the EF spectrum.

Reduced stroke volume by resting 2-dimensional echocardiography negatively affects survival in patients with abnormal ejection fraction

Abstract Background Abnormal (&amp;lt;50%) ejection fraction (EF) is a cornerstone of risk stratification and therapy, but also an imperfect proxy of left ventricular (LV) cardiac pump function, better assessed with stroke volume (SV). Aim To assess the value of SV in stratifying risk of patients with abnormal EF. Methods In a prospective, observational, multicenter study, we recruited 746 patients (age 66± 11 years, 536 males, 72%, 359 with previous myocardial infarction, 48%) with chronic coronary syndromes (CCS) and EF &amp;lt;50% referred for resting transthoracic echocardiography with technically successful 2-dimensional volumetric echocardiography in 17 accredited laboratories. We quantitatively assessed LV end-diastolic volume (EDV) and end-systolic volume (ESV) by Simpson’s biplane method. EF (EDV-ESV/EDV) and SV (EDV-ESV) were calculated from LV volumes. The outcome end-point was all-cause death. Results EF was 39±9%, SV 48±20 ml. There were 100 all-cause deaths during a median follow-up of 796 days (interquartile range 420-1286 days). Receiver-operating curve analysis identified SV≤31.4 ml/b as the best cut-off for predicting mortality. At multivariable analysis, after adjustment for age and prior myocardial infarction, EF &amp;lt;40% and SV ≤31.4 ml/b were significantly associated with decreased survival (HR 2.09, 95%, confidence intervals 1.09-4.01, p=0.024). The annual mortality was lowest (3.19%) in the group with mildly reduced (40-49%) EF and normal (&amp;gt;31.4 ml) SV, and highest (8.30%) in patients with both reduced EF and abnormal SV: see figure. Conclusion Patients with CCS and abnormal EF are a prognostically heterogeneous group, and the mortality rate is almost 3-times worse in patients with reduced EF and abnormal SV compared to patients with mildly reduced EF and normal SV. A simple resting volumetric two-dimensional echocardiography can offer an efficient risk stratification, beyond EF, with no extra imaging or analysis time.Figure

Changing patterns in clinical, echocardiographic and haemodynamic characteristics, and management strategies that may be translated to improved survival in pulmonary hypertension

Abstract Background and aims In this retrospective analysis of a single-center series on pulmonary hypertension (PH), we aimed to evaluate clinical, echocardiographic, and hemodynamic characteristics, management strategies, morbidity, and mortality in PH subgroups across three consecutive periods. Methods The study included 1071 patients enrolled in the Evaluation of Pulmonary Hypertension Risk factors Associated with Survival study (EUPHRATES). In reference to enrollment time, patients were assessed in three periods ; before 2016, the era of primarily monotherapy or sequential combinations; between 2016 and 2019, post-approval and reimbursement of macitentan in our country, marking a shift towards more proactive sequential combinations; and after 2019, signifying the initiation of earlier sequential combinations with selexipag in pulmonary arterial hypertension (PAH). The ESC/ERS 2022 risk scoring, COMPERA 2.0 and REVEAL lite 2 models were used for risk predictions. Composite endpoint (CEP) definitions were adopted from the SERAPHIN and GRIPHON trials. Annual incidence curves for mortality and CEP were evaluated, but 2020 analysis was adjusted to account for the possible adverse effects of the COVID-19. Results During the 1st, 2nd and 3rd periods, 481, 352, and 238 patients with PH were diagnosed, respectively. Incident cases comprised 91% of them. Idiopathic PAH (IPAH), PAH-associated with congenital heart diseases (CHD-PAH), PAH-associated with connective tissue diseases (CTD-PAH), group II, III, IV and V PH were documented in 24 %, 28 %, 4.6 %, 4.3 %, 11%, 27 % and 0.7 % of patients, respectively. Age and female dominance remained unchanged. Incidences of Group 1 PH and CHD-PAH decreased while IPAH, drug-associated PAH, and Group II and IV PH increased across three periods (p-values varying from &amp;lt;0.001 to 0.03). Although baseline functional class became worse (p=0.013), six-minute walk distance, N-terminal pro brain natriuretic peptide and risk scores showed no change (p=NS). Baseline echo and hemodynamic measures became better, and triple combinations increased after 2019 (p&amp;lt;0.001 for all). For overall PH, rates of all-cause mortality and CEPs at 1st, 2nd and 3rd periods were 52 % and 59 %, 30 % and 35 %, and 11 % and 13 %, respectively (p&amp;lt; 0.001, for all). Mortality rates for 1st, 2nd and 3rd periods were 36 %, 38 % and 26 % in IPAH, 60 %, 28 % and 13 % in CHD-PAH, 55 %, 22% and 22% in CTD-PAH, 38 %, 38% and 24 % in group IV PH, respectively (p&amp;lt; 0.001, for all). Mortality curves showed sudden increases in 2020, but excluding 2020, a steady improvement in the annual mortality was evident. Conclusions Our findings suggest a trend towards better clinical, echocardiographic, and hemodynamic presentations and improved survival in the PAH subgroups, and Group IV PH across the three periods that might be attributed to more proactive management strategies favouring earlier initiation of combinations.

Prognostic significance of coronary flow velocity reserve in patients with peripheral arterial disease

Abstract Background Patients with lower extremity peripheral arterial disease (PAD) have a higher risk of cardiovascular events. Stress echocardiography (SE) based on regional wall motion abnormality (RWMA) is imperfect for risk stratification in PAD, but it can be complemented with an assessment of coronary flow velocity reserve (CFVR) in the mid-distal left anterior descending coronary artery. Purpose To assess the value of SE with RWMA and CFVR to predict survival in PAD. Methods In a retrospective analysis of prospectively acquired data in an observational, multicenter study, we recruited 359 patients (age 69±8 years, 240 [67%] males) with PAD referred for dipyridamole SE in 3 accredited laboratories. We assessed RWMA and CFVR (abnormal value &amp;lt;2.0). All patients were followed up for a median of 4.7 (interquartile range: 2.0 to 8.2 years). All-cause death was the outcome end-point. Results The positivity rate was 37/359 (10%) for RWMA and 159/359 (44%) for CFVR. During follow-up, 97 (27%) deaths were registered. At multivariable analysis, inducible RWMA and/or CFVR &amp;lt;2.0 (HR 2.58, 95% CI 1.65-4.04; p&amp;lt;0.0001), age ≥70 years, diabetes, dialysis treatment, and ejection fraction ≤50% were associated with decreased survival. The annual mortality was 7.4% in patients with RWMA and/or CFVR &amp;lt;2.0 and 2.7% in those with no RWMA and CFVR &amp;gt;2.0 (Figure, p&amp;lt;0.0001). Conclusion In patients with PAD, SE shows more than 4-fold higher prevalence of abnormal CFVR compared to RWMA. The prognostic value of CFVR outperforms RWMA, showing the importance of coronary microvascular dysfunction and diffuse, subcritical coronary atherosclerosis in determining the outcome.

Insights into the aetiology and temporal trends in cardiac mortality in the young: a 21-year review of national and registry data in the united kingdom

Abstract Background An accurate representation of the incidence and aetiology of cardiac and sudden cardiac death (SCD) is vital for healthcare policymakers to effectively allocate resources for preventative strategies. Purpose We aimed to report on the incidence and causes of cardiac and SCD among individuals under 35-years-old in England and Wales for 21 years (2001-2021), with a focus on identifying any temporal trends. Methods Annual mortality data from the Office for National Statistics (ONS) pertaining to cardiovascular (CV) and possible CV deaths in individuals under 35-years-old were analyzed using International Classification of Diseases-10 codes. Deaths were categorized into four-classes: A1- definitive cardiac deaths without identifiable structural heart disease (consistent with sudden arrhythmic death syndrome, SADS); A2- definitive cardiac deaths with identified structural heart disease; A3- definitive cardiac deaths with indeterminate cause; and B- potential cardiac deaths. Incidence rates were computed based on annual ONS census data. Additionally, insights were gleaned from the Cardiac Risk in the Young Centre for Cardiac Pathology (CRYCCP) nationwide registry. Results The mean annual number of definitive cardiac deaths (classes A1+A2+A3) was 414 (SD 27.4), resulting in an incidence of young cardiac and SCD of 1.68/100,000 individuals/year. Ischaemic heart disease (28.4%), cardiomyopathies (25.9%), and SADS (21.8%) were the most prevalent cardiac conditions. Cardiomyopathies and SADS related mortality peaked in the 10-to-19 age group, while ischaemic heart disease peaked in the 30-to-35 age group. A mean of 573 (SD 76.6) possible cardiac deaths (class B) occurred, these primarily included ill-defined causes (33.5%), epilepsy (32.4%), sudden infant death syndrome (24.2%), and drowning (7%). Definitive and possible cardiac deaths showed a male preponderance (male to female ratios: 2.3:1 and 1.6:1, respectively). A declining trend in cardiac mortality was observed with a 1.3% (95%CI: 1.0%-1.7%) incidence rate reduction/year (p&amp;lt;0.001). This was associated with a 2.5% annual incidence rate reduction for deaths attributed to structural heart disease (p&amp;lt;0.001), but an 8.5% annual incidence rate increase for deaths attributed to SADS (p&amp;lt;0.001). These trends corelated with increasing numbers of deaths referred to the CRYCCP where an expert cardiac pathologist diagnosed SADS in over 52% of cases. Conclusions Over 21 years in England and Wales, national datasets suggest the incidence of young cardiac and SCD is 1.68/100,000/year, with a small but appreciable declining mortality trend. The rise in SADS rates and contemporaneous decline in deaths attributed to structural heart disease may signify increased awareness and accessibility to expert cardiac pathologists. Ensuring accurate mortality coding is crucial for thoroughly assessing first-degree family members in cases of suspected inherited cardiac conditions.

When does annual geriatric hip fracture mortality revert to baseline?

BackgroundGeriatric hip fracture patients exhibit high mortality post-injury. It's unclear if and when mortality reverts to baseline. We therefore ask, When, if ever, does the mortality rate of geriatric hip fracture revert to the population-wide baseline rate? How does the mortality rate after geriatric hip fracture compare to the population norms? Understanding this timeline is crucial for assessing disease burden and guiding treatment plans.MethodsA cohort of 17,868 male patients aged 65–89 years treated for hip fracture within the VA healthcare system was studied. Patients were grouped by age at the time of fracture, and age-specific fractional survival was assessed annually for 10 years. For a comparison control group, a virtual cohort of 17,868 individuals, mirroring the age distribution of the patient group, was created and reduced over 10 cycles according to Social Security Administration expected mortality statistics.ResultsThe year-one mortality rate among fracture patients was 35.4%, compared to 6.3% in age-matched controls. By year ten, only 8.5% of the fracture patients remained alive, vs. 39.8% in the general population. The annual risk of dying for patients who survived past the first year was consistently in the range 19%–21% for all subsequent years.ConclusionHip fracture patients who survive the initial injury are still subject to annual mortality risk of approximately 20%, an elevation above population norms persisting for at least a decade. The data underscores the severity of geriatric hip fractures, and suggest that focusing one- or two-year survival rates may not fully capture the severity of the injury.

Influence of stream temperature and human disturbance on prespawn mortality of Chinook Salmon in the Willamette River basin

AbstractObjectivePremature mortality of adult female Chinook Salmon Oncorhynchus tshawytscha is a major barrier to population recovery. The Willamette River basin, Oregon, typifies the problems that are faced by fishery managers in the Pacific Northwest (USA). Adult salmon are trapped and transported upstream of dams to access historical spawning grounds, but annual rates of prespawn mortality (PSM) are high (often &gt;40%) and may limit the recovery of natural populations. The purpose of this study was to identify potential factors related to PSM of female Chinook Salmon that are outplanted above dams and incorporate them into a modeling framework to facilitate adaptive management of outplanting operations.MethodsWe evaluated PSM in Fall Creek of the Willamette River basin prior to transport facility improvements in summer and fall of 2010–2017 and postimprovement during 2020–2021. We estimated PSM and conducted exploratory analyses to identify possible nontransport sources of stress that may contribute to the observed high PSM rates. Candidate factors included long‐term elevated temperature exposure, elevated temperature exposure below the trap, total number of outplanted fish, and monthly human disturbance of outplanted fish. We then developed and fit three models, each representing a hypothesis of a factor influencing PSM, incorporated them into a single alternative decision model, and conducted sensitivity analyses.ResultPrespawn mortality averaged 0.66 (ranging from 0.37 to 0.94) over the study period. According to the simulation results, the top two management actions were to exclude human activities—swimming and fishing—from Fall Creek in July and August.ConclusionExpected PSM rates were predicted to be 0.38 when human activity was excluded in July and 0.37 for August. Sensitivity analyses indicated that the most influential decision model component was the choice of the alternative model.

Effects of Alkaline Solutions on the Structure and Function of Influenza A Virus

Influenza A virus (IAV) infection contributes to high annual morbidity and mortality, thus necessitating measures aimed at protecting against the disease. Alcohol-based disinfectants are commonly used to inactivate IAV, but they have several undesirable properties. In search of other means which would inactivate IAV, we focused on the effect of alkaline solutions on IAV. We found the viral infectivity remarkably decreased with treatment of an alkaline solution at pH 12.0 for 1 min, where destruction of the viral spikes was observed using an electron microscope. A more detailed examination revealed that the infectivity of IAV was remarkedly reduced by brief treatment with the alkaline solution at pH 11.75 or above, most likely due to the degradation of viral hemagglutinin protein. These results show that at a high pH, the haemagglutinin protein is degraded, resulting in very rapid inactivation of IAV.

Defining and Validating Criteria to Identify Populations Who May Benefit From Home-Based Primary Care.

Home-based primary care (HBPC) is an important care delivery model for high-need older adults. Currently, target patient populations vary across HBPC programs, hindering expansion and large-scale evaluation. Develop and validate criteria that identify appropriate HBPC target populations. A modified Delphi process was used to achieve expert consensus on criteria for identifying HBPC target populations. All criteria were defined and validated using linked data from Medicare claims and the National Health and Aging Trends Study (NHATS) (cohort n=21,727). Construct validation involved assessing demographics and health outcomes/expenditures for selected criteria. Delphi panelists (n=29) represented diverse professional perspectives. Criteria were validated on community-dwelling Medicare beneficiaries (age above 70) enrolled in NHATS. Criteria were selected via Delphi questionnaires. For construct validation, sociodemographic characteristics of Medicare beneficiaries were self-reported in NHATS, and annual health care expenditures and mortality were obtained via linked Medicare claims. Panelists proposed an algorithm of criteria for HBPC target populations that included indicators for serious illness, functional impairment, and social isolation. The algorithm's Delphi-selected criteria applied to 16.8% of Medicare beneficiaries. These HBPC target populations had higher annual health care costs [Med (IQR): $10,851 (3316, 31,556) vs. $2830 (913, 9574)] and higher 12-month mortality [15% (95% CI: 14, 17) vs. 5% (95% CI: 4, 5)] compared with the total validation cohort. We developed and validated an algorithm to define target populations for HBPC, which suggests a need for increased HBPC availability. By enabling objective identification of unmet demands for HBPC access or resources, this algorithm can foster robust evaluation and equitable expansion of HBPC.

Mortality of alzheimer's disease in Italy from 1980 to 2015.

To evaluate mortality for Alzheimer's Disease (AD) in Italy over more than three decades (1980-2015) and discuss the possible role of general and specific contributing factors. Mortality data were extracted by the Italian National Institute of Statistics: crude mortality rates were computed for sex and age, considering the whole country and its five main geographical sub-areas. Rates were standardized in two ways: directly (annual mortality rates AMRs) and indirectly (standardized mortality rates, SMRs). SMRs were then used to evaluate geographical differences; to study mortality trend, AMRs and joinpoint linear regression analysis were used. Considering the entire period and the whole country, mortality rates were similar for females and males and for geographical regions, with the exception of the older age groups where mortality for AD in females slightly prevailed. In these older patients, a steep increase of mortality was seen starting from the current century. The increase in male mortality mirrored the national trend in North-West and Central Italy, but not in North-East, South, and the Islands, where it did not surge until the mid to late 1990s. the general increase of mortality is in line with international data and it reflects the increasing prevalence of the disease, likely due to increasing longevity, and to improvements in diagnostic accuracy. In addition, the accuracy of death certificate compilation could account for both geographical and temporal differences. Currently available drugs for AD do not seem to have an impact on mortality rates.

Computational model for policy simulation and prediction of the regulatory impact of front-of-package food labels

Non-communicable diseases (NCDs), a significant cause of global mortality, necessitate targeted policy measures to reduce exposure to risk factors, particularly nutrition-related ones. Front-of-pack food labeling aims to shape consumer behavior and decrease exposure to nutritional risk factors. There are various forms of this policy, including traffic light (TL), nutrient profile model (NPM), and reference value (RV) labels. Mathematical models incorporating experimental and dose–response data support determining the most effective form. When selecting a modeling method, it is essential to consider the uncertainty involved in estimating risk factors. This study aims to create a computational model to predict the health and economic impacts of different policy options using an improved version of the Scarborough algorithm, incorporating a validation process to address potential uncertainties. The model shows that NPM was the most effective, reducing the estimated annual mortality rate from 514,247 cases to 447,394 cases (13% reduction). The following labels were TL (11% reduction) and RV (6% reduction). Economically, the RV label affects consumer spending the least, predicting an 8% increase in monthly spending per individual from the baseline. When assessed from both health and economic perspectives, the RV label has emerged as the most advantageous front-of-pack food labeling policy. The proposed model can aid policymakers in evaluating policy alternatives and thus selecting the most advantageous policies based on health and economic outcomes while ensuring the model's accuracy and applicability for the community.

Estimating the lives that could be saved by expanded access to weight-loss drugs

Obesity is a major public health crisis in the United States (US) affecting 42% of the population, exacerbating a spectrum of other diseases and contributing significantly to morbidity and mortality overall. Recent advances in pharmaceutical interventions, particularly glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, liraglutide) and dual gastric inhibitory polypeptide and GLP-1 receptor agonists (e.g., tirzepatide), have shown remarkable efficacy in weight-loss. However, limited access to these medications due to high costs and insurance coverage issues restricts their utility in mitigating the obesity epidemic. We quantify the annual mortality burden directly attributable to limited access to these medications in the US. By integrating hazard ratios of mortality across body mass index categories with current obesity prevalence data, combined with healthcare access, willingness to take the medication, and observed adherence to and efficacy of the medications, we estimate the impact of making these medications accessible to all those eligible. Specifically, we project that with expanded access, over 42,000 deaths could be averted annually, including more than 11,000 deaths among people with type 2 diabetes. These findings underscore the urgent need to address barriers to access and highlight the transformative public health impact that could be achieved by expanding access to these novel treatments.

The state of cancer care in Russia: pancreatic cancer (C25). Diagnosis, prevalence, quality of accounting, typical mortality. Part 1. (clinical and population-based research)

The study focuses on pancreatic cancer (C25), a malignant neoplasm arising from the ductal epithelium or glandular tissue of the pancreas, which accounts for 3% of the overall cancer incidence in Russia. The rates of incidence and mortality are rising, with the number of newly registered patients in Russia being lower than the number of recorded deaths, although the one-year mortality rate among patients is decreasing. The direct cause of pancreatic cancer (C25) remains unknown. Risk factors for developing this condition include genetics, smoking, alcohol abuse, a sedentary lifestyle, excessive meat consumption, and a lack of plant-based foods in the diet. Diseases associated with a high risk of this pathology include long-standing chronic pancreatitis, newly diagnosed type 2 diabetes in individuals aged 50-70, and cystic neoplasms of the pancreas. The aim of the study is to examine the patterns of incidence and mortality, the quality of patient registration, the characteristics of tumor localization, and the histological structure of pancreatic cancer (C25). The study will also track the nature of annual mortality among patients and explore the possibilities, methods, and techniques of modern diagnosis and treatment for these patients. The research confirmed the significant burden of pancreatic cancer (C25), primarily due to the late detection of this disease. The study provided sufficient material to analyze age-related risk factors, as well as the patterns of incidence and mortality in the population. It also examined and presented mortality rates among patients, including during the first year of observation.

A five-year retrospective review of fatalities involving novel psychoactive substances in Southern Ireland

Introduction: Novel psychoactive substances (NPS) are rapidly emerging and being reformulated to evade legislative controls, creating unpredictability in drug markets and ineffective drug policies. Given that Ireland has the highest self-reported NPS use within Europe and literature regarding health risks is lacking, the National Advisory Committee on Drugs has advocated for the surveillance of regional trends. Objectives: To elucidate the demographic and autopsy findings of fatal cases involving NPS in Southern Ireland as compared to deaths involving traditional drugs of abuse (TDOA). Methods: Post-mortem reports from the Cork-Kerry region with positive toxicology for illicit substances between 2012-2016 were retrospectively analyzed to compare NPS and TDOA cases with respect to circumstances surrounding death, toxicological results, and pathological findings. Results: Between 2012-2016, there were 164 cases involving illicit substances in the Cork-Kerry region. NPS accounted for 17 (10.4%) cases, with an average annual mortality rate of 34.8 per 100,000 population. NPS contributed to the cause of death in 70.6% of cases where detected, compared to 43.5% for TDOA only. In both cohorts, fatal abusers were predominantly young males. Importantly, cases involving NPS showed a higher proportion of mono-drug intoxication and presentation to hospital prior to death. Autopsy findings were non-specific but commonly featured pulmonary congestion, aspiration, and cerebral oedema. Conclusion: NPS are detected in a small proportion of medicolegal autopsies but contribute significantly to acute intoxication deaths. This study highlights the need for effective drug monitoring and enforcement strategies, along with improved management of drug toxicities presenting to hospital.

Evolving epidemiological patterns of thyroid cancer and estimates of overdiagnosis in 2013–17 in 63 countries worldwide: a population-based study

The incidence of thyroid cancer has been increasing in many countries, mainly due to overdiagnosis. Given these rapid changes, we aim to assess the specific features of the thyroid cancer diagnosis epidemic and provide estimates of overdiagnosis across countries spanning five continents and identify areas in which coping strategies are needed. Two types of data were retrieved from the International Agency for Research on Cancer (IARC) Global Cancer Observatory database. The long-term annual incidence of thyroid cancer by sex and 5-year age group for all ages from 1980 to 2017 was obtained from continuous population-based registries available in the Cancer Incidence in Five Continents (CI5) plus, with 97 registries from 43 countries selected. Sex-age-specific thyroid cancer cases, overall and by subtype, along with corresponding population counts were retrieved from all registries included in the latest volume of CI5 (CI5-XII), with 385 registries in 63 countries. Annual mortality data from 1980 to 2022 were obtained from WHO, with population counts supplemented by UN population estimates. We estimated age-standardised rates (ASRs) of thyroid cancer incidence and mortality for all ages by sex using direct age standardisation, with the world population as a reference. Long-term annual trends of ASRs were compared between incidence and mortality since 1980. Subtype distribution was calculated for thyroid cancer incidence during 2013-17. We estimated the numbers of thyroid cancer cases and overdiagnosed cases and extrapolated to the whole country using a previously developed and validated method. Thyroid cancer incidence rates rose during 1980-2017 for most countries, with the highest rates seen in South Korea, Cyprus, Ecuador, China, and Türkiye for females and males. An upward trend was seen until the early 2010s, followed by a downward trend in South Korea, the USA, Canada, and Israel and some Western European countries, such as France, Italy, Austria, and Ireland. The difference between the highest and lowest incidence rates ranged from less than 10·0 per 100 000 females in the early 1980s to 101·4 per 100 000 females in 2012. For males, the difference between the highest and lowest incidence rates ranged from 2·7 per 100 000 to 23·5 per 100 000 over the study period. Mortality rates were substantially lower, with a difference between the highest and lowest rates across countries of around 1·0-2·0 per 100 000 for both sexes throughout the study period. During 2013-17, papillary thyroid cancer contributed to the large variation in ASRs of thyroid cancer incidence. The mortality rates of thyroid cancer increased with age for all countries, whereas the observed age-specific incidence rates showed an inverted U-shape in most countries. The magnitude of overdiagnosis varied across countries, ranging from no overdiagnosis (in Uganda, Zimbabwe, and Trinidad and Tobago) to more than 85·0% of thyroid cancer cases being overdiagnosed in females (in Cyprus, China, South Korea, and Türkiye). Overall, 1 736 133 (75·6%) of 2 297 057 cases were attributable to overdiagnosis, including 1 368 181 females and 367 952 males. Although the incidence of thyroid cancer has reached a plateau or decrease in some high-income countries, the magnitude of overdiagnosis is still very large and the expansion of overdiagnosis of thyroid cancer to the transitioning countries has been rapid, which makes it a global public health challenge that needs to be addressed. National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Young Talents Program of Sun Yat-sen University Cancer Center, Italian Association for Cancer Research, and the Italian Ministry of Health (Ricerca Corrente).

CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2017-2021.

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. Between 2017 and 2021, the average annual age-adjusted incidence rate (AAAIR) of all primary malignant and non-malignant brain and other CNS tumors was 25.34 per 100,000 population (malignant AAAIR=6.89 and non-malignant AAAIR=18.46). This overall rate was higher in females compared to males (28.77 versus 21.78 per 100,000) and non-Hispanic Black persons compared to persons who were non-Hispanic White (26.60 versus 25.72 per 100,000), non-Hispanic American Indian/Alaska Native (23.48 per 100,000), non-Hispanic Asian or Pacific Islander (19.86 per 100,000), and Hispanic persons of all races (22.37 per 100,000). Gliomas accounted for 22.9% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (13.9% of all tumors and 51.5% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (41.7% of all tumors and 56.8% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.02 per 100,000 population. There were 87,053 deaths attributed to malignant brain and other CNS tumors between 2017 and 2021. This represents an average annual mortality rate of 4.41 per 100,000 population and an average of 17,411 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain or other CNS tumor was 35.7%. For a non-malignant brain or other CNS tumor the five-year relative survival rate was 92.0%.

Increasing access to biomarker-driven treatment for lung cancer in Alabama: The Alabama Access initiative.

159 Background: Lung cancer is the leading cause of cancer death in Alabama, with an estimated 2,550 deaths in 2024. Non-small cell lung cancer (NSCLC) represents 85% of these cases. Despite national guidelines recommending comprehensive biomarker testing (CBT) for metastatic NSCLC, significant disparities persist in the utilization of CBT and targeted therapies among Alabama residents. Methods: In March 2024, we launched the "Alabama Access" initiative – a partnership between the LUNGevity Foundation and the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham – to foster academic and community oncology partnerships to increase access to biomarker-driven treatments. We used a population health science and geospatial mapping approach to visualize oncology practices serving counties with Alabama's highest lung cancer burden. Practices in Walker, Dothan, Marengo, Morgan, Jackson, Marshall, and Montgomery counties were identified as the highest priority based on annual mortality rates. Key interventions will include virtual molecular tumor boards and oncology navigation to facilitate the integration of resources and expertise and ensure that patients in nonacademic practices benefit from the latest advances in precision oncology. After roll-out, we will collect feasibility and acceptability data around program integration. Results: Our analysis revealed that 62.0% of the state’s population resides in Primary Care Health Professional Shortage Areas (HPSAs), and 58 out of 67 counties are classified as Medically Underserved Areas. The poverty rate in 89.6% of counties surpasses the national average, contributing to higher lung cancer incidence and mortality rates, with 62.0% of cases diagnosed at advanced stages. The state also shows a higher smoking prevalence, affecting 97.0% of counties compared to national figures. We will present practice-level testing data, including barriers to CBT. Conclusions: This pilot aims to mitigate disparities in CBT through enhanced collaboration between academic and community oncology settings. Integrating molecular navigation into community practices will be pivotal in disseminating program information and collecting data on current testing practices to improve overall lung cancer care quality in Alabama.

Influenza vaccine allocation in tropical settings under constrained resources.

Influenza virus seasonality, synchronicity, and vaccine supply differ substantially between temperate and tropical settings, and optimal vaccination strategy may differ on this basis. Many national vaccine recommendations focus on high-risk groups, elderly populations, and healthcare workers despite previous analyses demonstrating broad benefits to vaccinating younger high-contact age groups. In this study, we parameterized an age-structured nonseasonal asynchronous epidemiological model of influenza virus transmission for a tropical low-income setting. We evaluated timing and age allocation of vaccines across vaccine supplies ranging from 10 to 90% using decade-based age groups. Year-round vaccination was beneficial when compared with more concentrated annual vaccine distribution. When targeting a single age group for vaccine prioritization, maximum vaccine allocation to the 10-19 high-contact age group minimized annual influenza mortality for all but one vaccine supply. When evaluating across all possible age allocations, optimal strategies always allocated a plurality of vaccines to school-age children (10-19). The converse, however, was not true as not all strategies allocating a plurality to children aged 10-19 minimized mortality. Allocating a high proportion of vaccine supply to the 10-19 age group is necessary but not sufficient to minimize annual mortality as distribution of remaining vaccine doses to other age groups also needs to be optimized. Strategies focusing on indirect benefits (vaccinating children) showed higher variance in mortality outcomes than strategies focusing on direct benefits (vaccinating the elderly). However, the indirect benefit approaches showed a lower mean mortality and a lower minimum mortality than vaccination focused on the elderly.