Excess Mortality Research Articles

Age at death during the Covid-19 lockdown in French metropolitan regions: a non parametric quantile regression approach

BackgroundLockdowns have been implemented to limit the number of hospitalisations and deaths during the first wave of 2019 coronavirus disease. These measures may have affected differently death characteristics, such age and sex. France was one of the hardest hit countries in Europe with a decreasing east–west gradient in excess mortality. This study aimed at describing the evolution of age at death quantiles during the lockdown in spring 2020 (17 March—11 May 2020) in the French metropolitan regions focusing on 3 representatives of the epidemic variations in the country: Bretagne, Ile-de-France (IDF) and Bourgogne-Franche-Comté (BFC).MethodsData were extracted from the French public mortality database from 1 January 2011 to 31 August 2020. The age distribution of mortality observed during the lockdown period (based on each decile, plus quantiles 1, 5, 95 and 99) was compared with the expected one using Bayesian non-parametric quantile regression.ResultsDuring the lockdown, 5457, 5917 and 22 346 deaths were reported in Bretagne, BFC and IDF, respectively. An excess mortality from + 3% in Bretagne to + 102% in IDF was observed during lockdown compared to the 3 previous years. Lockdown led to an important increase in the first quantiles of age at death, irrespective of the region, while the increase was more gradual for older age groups. It corresponded to fewer young people, mainly males, dying during the lockdown, with an increase in the age at death in the first quantile of about 7 years across regions. In females, a less significant shift in the first quantiles and a greater heterogeneity between regions were shown. A greater shift was observed in eastern region and IDF, which may also represent excess mortality among the elderly.ConclusionsThis study focused on the innovative outcome of the age distribution at death. It shows the first quantiles of age at death increased differentially according to sex during the lockdown period, overall shift seems to depend on prior epidemic intensity before lockdown and complements studies on excess mortality during lockdowns.

Coronary revascularization and sex differences in cardiovascular mortality after myocardial infarction in 12 high and middle-income European countries.

Existing data on female sex and excess cardiovascular mortality after myocardial infarction (MI) mostly come from high-income countries (HICs). This study aimed to investigate how sex disparities in treatments and outcomes vary across countries with different income levels. Data from the ISACS-Archives registry included 22087 MI patients from 6 HICs and 6 middle-income countries (MICs). MI data were disaggregated by clinical presentation: ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). The primary outcome was 30-day mortality. Among STEMI patients, women in MICs had nearly double the 30-day mortality rate of men (12.4% versus 5.8%; adjusted risk ratio [RR] 2.30, 95% CI 1.98-2.68). This difference was less pronounced in HICs (6.8% versus 5.1%; RR 1.36, 95% CI 1.05-1.75). Despite more frequent treatments and timely revascularization in MICs, sex-based mortality differences persisted even after revascularization (8.0% versus 4.1%; RR 2.05, 95% CI, 1.68-2.50 in MICs and 5.6% versus 2.6%; RR 2.17, 95% CI 1.48-3.18) in HICs. Additionally, women from MICs had higher diabetes rates compared to HICs (31.8% versus 25.1%, standardized difference=0.15). NSTEMI outcomes were relatively similar between sexes and income groups. Sex disparities in mortality rates following STEMI are more pronounced in MICs compared to HICs. These disparities cannot be solely attributed to sex-related inequities in revascularization. Variations in mortality may also be influenced by sex differences in socioeconomic factors and baseline comorbidities.

Conventional and frugal methods of estimating COVID-19-related excess deaths and undercount factors

Across the world, the officially reported number of COVID-19 deaths is likely an undercount. Establishing true mortality is key to improving data transparency and strengthening public health systems to tackle future disease outbreaks. In this study, we estimated excess deaths during the COVID-19 pandemic in the Pune region of India. Excess deaths are defined as the number of additional deaths relative to those expected from pre-COVID-19-pandemic trends. We integrated data from: (a) epidemiological modeling using pre-pandemic all-cause mortality data, (b) discrepancies between media-reported death compensation claims and official reported mortality, and (c) the “wisdom of crowds” public surveying. Our results point to an estimated 14,770 excess deaths [95% CI 9820–22,790] in Pune from March 2020 to December 2021, of which 9093 were officially counted as COVID-19 deaths. We further calculated the undercount factor—the ratio of excess deaths to officially reported COVID-19 deaths. Our results point to an estimated undercount factor of 1.6 [95% CI 1.1–2.5]. Besides providing similar conclusions about excess deaths estimates across different methods, our study demonstrates the utility of frugal methods such as the analysis of death compensation claims and the wisdom of crowds in estimating excess mortality.

Survival analysis and gender differences in hypertrophic cardiomyopathy proband patients referred for genetic testing

BackgroundHypertrophic cardiomyopathy (HCM) is believed to have low overall mortality rate, that could be influenced by gender, particularly among probands. We aimed to evaluate the survival rates and possible gender differences in a homogeneous cohort of HCM proband patients, referred for genetic testing, from the same geographical area, without differences in medical care access nor clinical referral pathways. Methodswe compared the mortality rates of a cohort of consecutive HCM probands referred for genetic testing (2000−2022), from a Spanish region (xxx1) with a centralized genetic testing pathway, with its control reference population by Ederer II method. Gender differences were analyzed. ResultsAmong the 649 HCM probands included in this study, there were significantly more men than women (61.3% vs 38.7, p < 0.05), with an earlier diagnosis (53.5 vs 61.1 years old, p < 0.05). Clinical evolution or arrhythmogenic HCM profile did no show no significant gender differences. Mean follow up was 9,8 years ±6,6 SD (9,9 ± 7 vs 9,6 ± 6,1, p = 0.59). No statistically significant differences in observed mortality, expected survival and excess mortality were found in the general HCM proband cohort. However, we found a significant excess mortality in female probands with HCM. No additional differences in analysis by genetic status were identified. ConclusionExpected survival in our HCM probands did not differ from its reference population. However, despite no gender differences in phenotype severity were identified, proband HCM women did present a diagnosis delay and worse mortality outcomes.

Interaction between mental disorders and social disconnectedness on mortality: a population-based cohort study.

Despite the recognised importance of mental disorders and social disconnectedness for mortality, few studies have examined their co-occurrence. To examine the interaction between mental disorders and three distinct aspects of social disconnectedness on mortality, while taking into account sex, age and characteristics of the mental disorder. This cohort study included participants from the Danish National Health Survey in 2013 and 2017 who were followed until 2021. Survey data on social disconnectedness (loneliness, social isolation and low social support) were linked with register data on hospital-diagnosed mental disorders and mortality. Poisson regression was applied to estimate independent and joint associations with mortality, interaction contrasts and attributable proportions. A total of 162 497 individuals were followed for 886 614 person-years, and 9047 individuals (5.6%) died during follow-up. Among men, interaction between mental disorders and loneliness, social isolation and low social support, respectively, accounted for 47% (95% CI: 21-74%), 24% (95% CI: -15 to 63%) and 61% (95% CI: 35-86%) of the excess mortality after adjustment for demographics, country of birth, somatic morbidity, educational level, income and wealth. In contrast, among women, no excess mortality could be attributed to interaction. No clear trends were identified according to age or characteristics of the mental disorder. Mortality among men, but not women, with a co-occurring mental disorder and social disconnectedness was substantially elevated compared with what was expected. Awareness of elevated mortality rates among socially disconnected men with mental disorders could be of importance to qualify and guide prevention efforts in psychiatric services.

Hospital Volume for Rectal Cancer Resection Plays a Pivotal Role in Improving Outcomes: A Population-based Analysis.

Assessing the association between hospital surgical volume (SV) and outcomes after rectal cancer surgery (RCS), using national population-based data. For RCS, the association of higher SV with improved short- and/or long-term outcomes remains controversial. National cancer registry data and administrative data were used to select patients diagnosed with stage I-III rectal cancer in 2009-2018 and who underwent RCS. The average annual SV of RCS was categorised as low (<15; LV), medium (15-29; MV) or high (≥30; HV). The association between SV and 90-day and 1-year excess postoperative mortality (90DPM and 1YEPM) and 5-year observed survival (5YOS) was evaluated. From the 11,519 patients , RCS was performed in LV (4,088; 36%), MV (2,795; 24%) or HV (4,636; 40%) hospitals. Observed 90DPM was significantly better in HV (2.3% 95%CI[1.9,2.8]) than in LV (3.7% 95%CI[3.2,4.4]) and MV (3.5% 95%CI[2.9,4.3]) with adjusted OR 1.4, P<0.0001. Continuous regression analysis showed significantly higher 90DPM in annual SV <35 compared to ≥35 (OR 1.6 95%CI[1.21,2.11]; P=0.0009). Observed 1YEPM was significantly better in HV (2.9% 95%CI[2.2,3.6]) compared to LV (4.7% 95%CI [3.9,5.6]) with adjusted excess HR 1.31 95%CI[1.00,1.73] and P=0.05, and to MV (5.0% 95%CI[4.0,6.1]) with adjusted excess HR 1.45 95%CI[1.09,1.94] and P=0.01. The 5YOS was significantly better in HV (75.9% 95%CI[74.6,77.2]) than in LV (70.3% 95%CI[68.8,71.8]) and MV (71.5% 95%CI[69.7,73.2]) with adjusted HR 1.4 in both LV and MV versus HV, P≤0.003. This population-based study identified robustly superior outcomes at 90-days, 1-year and 5-years after RCS in hospitals with higher volumes.

129 Evaluating effects of myostatin loss-of-function mutation on piglets for potential causes of early mortality

Abstract Pigs with an engineered myostatin loss-of-function mutation in exon 3 (-1T) experience perinatal mortality of unknown cause. From 36 litters resulting from matings of sows and boars both heterozygous for the mutation, 240 total piglets were born but only 14% (5/35) of piglets with myostatin loss-of-function mutation survived or were viable beyond postnatal d 3. Thus, the objective was to evaluate the effects of this myostatin loss-of-function mutation on piglet organ and muscle development and blood parameters to determine potential causes of this excess mortality. Blood was collected for complete blood count and then piglets (n = 50) were euthanized at postnatal d 3. Piglets were dissected and longissimus muscle, semitendinosus muscle, heart, liver, lungs, kidneys, pancreas, spleen, stomach, small intestine, large intestine, testicles or female reproductive tract, and tongue were weighed. Front girth, back girth, and snout to rump were measured. Loin samples were used to genotype piglets into one of three groups: wild type (WT; unmutated myostatin, n = 13), heterozygous (HET, n = 21) and myostatin mutant (MKO, n = 10). Data were analyzed as a two-way ANOVA using the MIXED procedure of SAS to determine the effect of sex, genotype, and their interaction. Body weight (P = 0.67) and front girth (P = 0.13) were not different between genotypes, but back girth was reduced (P = 0.04) in MKO by 2.3 cm compared with WT and by 2.1 cm compared with HET piglets. MKO piglets had lighter (P ≤ 0.03) hearts, livers, kidneys, pancreases, spleens, stomachs, and small intestine compared with HET and WT piglets, on both an absolute basis and as a percentage of body weight. In general, compared with other other genotypes, MKO organs were 5 to 19% lighter. Surprisingly, muscle weights, both longissimus and semitendinosus muscles, were not different (P ≥ 0.15) between genotypes, either on an absolute basis or as a percentage of body weight. White blood cell count was not different; however, neutrophil count was increased in MKO compared with other genotypes. These data suggest that underdeveloped or undersized organs in MKO piglets may compromise their survivability. Additionally, increased neutrophil counts may be indicative of a stress response in MKO piglets.

The short-term effects of individual and mixed ambient air pollutants on suicide mortality: A case-crossover study

It is critical to explore intervenable environmental factors in suicide mortality. Based on 30,688 suicide cases obtained from the Mortality Surveillance System of the Jiangsu Provincial Centre for Disease Control and Prevention, we utilized a case-crossover design, and found that the OR of suicide deaths increased by a maximum of 0.71 % (95 % CI: 0.09 %, 1.32 %), 0.68 % (95 % CI: 0.12 %, 1.25 %), 0.77 % (95 % CI: 0.19 %, 1.37 %), 2.95 % (95 % CI: 1.62 %, 4.29 %), 4.18 % (95 % CI: 1.55 %, 6.88 %), and 0.93 % (95 % CI: 0.10 %, 1.77 %), respectively, for per 10 μg/m3 increase in the particulate matter (PM) with diameters ≤ 2.5 µm (PM2.5), PM with diameters ≤ 10 µm (PM10), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), and per 0.1 mg/m3 increase in carbon monoxide (CO) concentrations with the conditional logistic regression analysis. People living in county-level cities were more susceptible. Particularly, a significant positive association was found between air pollutant mixture exposure and suicide deaths (OR=1.04,95 % CI: 1.01, 1.06). The excess fraction of suicide deaths due to air pollution reached a maximum of 8.07 %. In conclusion, we found associations between individual and mixed ambient air pollutants and suicide deaths, informing the development of integrated air pollution management and targeted measures for suicide prevention and intervention. Environmental ImplicationAs a major contributor to the global burden of disease, air pollution was confirmed by accumulating studies to have adverse impact on mental health, and potentially lead to suicide deaths. However, systematic studies on the association between air pollution and suicide mortality are lacking. We explored the associations of multiple air pollutants and pollution mixtures with suicide deaths and assessed excess suicide mortality due to air pollution, emphasizing the importance of air pollution control on suicide prevention. Our study provides evidence to support mechanistic studies on the association between air pollution and suicide, and informs comprehensive air pollution management.

Lower extremity arterial disease vs. coronary artery disease: mortality differences after revascularization.

Patients undergoing revascularization for lower extremity arterial disease (LEAD) may face a higher risk of mortality than those with coronary artery disease (CAD). This study aimed to characterize the difference in mortality risk between patients undergoing revascularization for LEAD and CAD and identify associated factors. The 1-year database of 10 754 patients undergoing revascularization for CAD (n = 6349) and LEAD (n = 4405) was analysed. Poisson regression models were used to characterize interpopulation differences in mortality, adjusting for baseline clinical features, including age, sex, polyvascular disease, comorbidities, medications, and vulnerabilities. Individuals with LEAD were older, were more likely to have polyvascular disease, had more comorbidities, and received fewer cardioprotective drugs than those with CAD. Vulnerabilities remained more common in the LEAD group even after adjusting for these clinical features. The crude risk ratio of mortality incidence for LEAD vs. CAD was 2.91 (95% confidence interval, 2.54-3.34), attenuated to 2.14 (1.83-2.50) after controlling for age, sex, and polyvascular disease. The percentage attenuation in the excessive mortality associated with LEAD was 29%. The stepwise addition of comorbidities, medications, and vulnerabilities as adjusting factors attenuated the incidence risk ratio to 1.48 (1.26-1.72), 1.33 (1.12-1.58), and 1.17 (0.98-1.39), respectively, and increased the percentage attenuation to 64%, 73%, and 86%, respectively. Mortality risk was almost three-fold higher in patients undergoing revascularization for LEAD than in those with CAD. The excessive mortality was considerably attributable to inter-group differences in baseline characteristics, including potentially clinically or socially modifiable factors.

Mortality from the 1944–1945 famine in Java, Indonesia

AbstractThis article examines the human toll of the 1944–1945 famine in Java, Indonesia's main island. It estimates birth and death rates for the Indonesian population in Java during 1941–1951. Using the net population loss method, the article approximates a net loss of 3.3 million people during the 1942–1945 Japanese occupation period. This includes 1.8 million excess deaths; 0.7 million during 1944 and 1.1 million during 1945. The remainder are 1.4 million missing births in 1944 and 1945, associated with the malnutrition of women of childbearing ages and physical separation of wives from husbands recruited by Japanese authorities for forced labour.

Abstract PO5-24-12: IRX5010, a Highly Selective RARγ Nuclear Receptor Agonist Compound Inhibits In Vivo Growth of Murine EMT-6 Triple Negative Breast Cancer and Human JIMT-1Her2+ Breast Cancer By Induction of Tumor-Infiltrating Effector Memory T-cells

Abstract Research Objectives and Rationale: Previously, RARγ agonism has been shown to play an essential role in CD8 T-cell-mediated immunity to infectious pathogens. However, we found no previous reports on effects of RARγ agonists on in vivo tumor growth of triple negative or Her2+ breast cancers. Here we explored whether RARγ could play a critical role in T-cell-mediated immunity in these breast cancers, using potent highly selective novel RARγ agonist compounds. Experimental methods and results: We synthesized and screened compounds for selective transactivation of RAR γ in reporter assays. Three highly potent compounds, demonstrating highly selective RARγ transactivation at less than one nanomolar concentrations, were selected for further evaluation of potential anti-cancer activities in vitro. None of the three evaluated compounds demonstrated significant inhibitory effects on in vitro growth of EMT-6 triple negative breast cancer cells at concentrations of 20-100 millimolar, indicating that the three compounds have insignificant direct inhibitory effects on EMT-6 cancer cell growth in vitro. We then examined the effects of one of the compounds in vivo in a syngeneic mouse model of EMT-6 triple negative breast cancer. Treatment with the most potent of the three compounds, IRX5010, demonstrated dose response inhibition of in vivo growth of EMT-6 tumors. Inhibition of tumor growth at day 17 relative to vehicle was 59% and 69% respectively in mice treated with IRX5010 at 10 or 25 mg/kg/day. A cohort treated with 50 mg/kg/day was sacrificed early on day 12 due to excessive weight loss and deaths of some of the animals. This cohort experienced a 73% inhibition of tumor growth relative to vehicle. Gross necropsies of animals in the 25 and 50 mg/kg/day dose groups did not show observable pathologic findings in any major organ. Flow cytometry was performed on freshly excised tumors on the day of termination of the in-life portion of the study in the 10 and 25 mg/kg/day dose groups. Tumors from mice treated with IRX5010 had increased intratumoral numbers of Total CD45+ cells; Total CD3+, Total CD4+, and Total CD8+ T-cells per mg of tumor tissue, relative to vehicle controls. IRX5010 treated mice also had increased intratumoral CD4+IL-17+ T-helper cells; and increased CD4+CD62L- and CD8+CD62L- T-effector memory T-cells per mg of tumor tissue relative to vehicle-treated control mice. We also conducted an experiment of treatment with IRX5010 in mice transplanted with human immune cells (to provide a human immune system) to examine its effects on xenografted human Her2+ JIMT-1 cancer cells. In this model, treatment with IRX5010 at 10 mg/kg/day resulted in a 17% inhibition of tumor growth relative to vehicle control over 26 days of treatment. Flow cytometric analysis showed that tumors from the IRX5010 treated mice contained increased numbers per mg of tumor tissue of intratumoral human CD8+ T-cells, most of which were CD8+ CD7- CD45RA+ terminally differentiated effector memory phenotype T-cells. Conclusions: Treatment with IRX5010, a potent and highly selective RARγ nuclear receptor agonist compound demonstrated substantial treatment effects relative to vehicle control on inhibition of growth of murine triple negative breast cancer in vivo, despite having essentially no growth inhibitory effect on these cells in vitro. Treatment of xenografted human Her2+ tumors in mice with humanized immune systems resulted in a moderate inhibition of Her2+ breast cancer growth relative to vehicle controls. In both models, treatment with IRX5010 induced tumor infiltrating T-lymphocytes of largely effector memory phenotypes, demonstrating an effect on the tumor immune microenvironment. These data identify RARγ and RARγ agonists as a new treatment target and novel treatment modality for breast cancers, especially for the highly unmet need for new and better treatments for triple negative breast cancer. Citation Format: Martin Sanders, Mary Topalovski, Vidyasagar Vuligonda. IRX5010, a Highly Selective RARγ Nuclear Receptor Agonist Compound Inhibits In Vivo Growth of Murine EMT-6 Triple Negative Breast Cancer and Human JIMT-1Her2+ Breast Cancer By Induction of Tumor-Infiltrating Effector Memory T-cells [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-24-12.

Preventable Premature Deaths from the Five Leading Causes of Death in Nonmetropolitan and Metropolitan Counties, United States, 2010-2022.

A 2019 report quantified the higher percentage of potentially excess (preventable) deaths in U.S. nonmetropolitan areas compared with metropolitan areas during 2010-2017. In that report, CDC compared national, regional, and state estimates of preventable premature deaths from the five leading causes of death in nonmetropolitan and metropolitan counties during 2010-2017. This report provides estimates of preventable premature deaths for additional years (2010-2022). 2010-2022. Mortality data for U.S. residents from the National Vital Statistics System were used to calculate preventable premature deaths from the five leading causes of death among persons aged <80 years. CDC's National Center for Health Statistics urban-rural classification scheme for counties was used to categorize the deaths according to the urban-rural county classification level of the decedent's county of residence (1: large central metropolitan [most urban], 2: large fringe metropolitan, 3: medium metropolitan, 4: small metropolitan, 5: micropolitan, and 6: noncore [most rural]). Preventable premature deaths were defined as deaths among persons aged <80 years that exceeded the number expected if the death rates for each cause in all states were equivalent to those in the benchmark states (i.e., the three states with the lowest rates). Preventable premature deaths were calculated separately for the six urban-rural county categories nationally, the 10 U.S. Department of Health and Human Services public health regions, and the 50 states and the District of Columbia. During 2010-2022, the percentage of preventable premature deaths among persons aged <80 years in the United States increased for unintentional injury (e.g., unintentional poisoning including drug overdose, unintentional motor vehicle traffic crash, unintentional drowning, and unintentional fall) and stroke, decreased for cancer and chronic lower respiratory disease (CLRD), and remained stable for heart disease. The percentages of preventable premature deaths from the five leading causes of death were higher in rural counties in all years during 2010-2022. When assessed by the six urban-rural county classifications, percentages of preventable premature deaths in the most rural counties (noncore) were consistently higher than in the most urban counties (large central metropolitan and fringe metropolitan) for the five leading causes of death during the study period.During 2010-2022, preventable premature deaths from heart disease increased most in noncore (+9.5%) and micropolitan counties (+9.1%) and decreased most in large central metropolitan counties (-10.2%). Preventable premature deaths from cancer decreased in all county categories, with the largest decreases in large central metropolitan and large fringe metropolitan counties (-100.0%; benchmark achieved in both county categories in 2019). In all county categories, preventable premature deaths from unintentional injury increased, with the largest increases occurring in large central metropolitan (+147.5%) and large fringe metropolitan (+97.5%) counties. Preventable premature deaths from CLRD decreased most in large central metropolitan counties where the benchmark was achieved in 2019 and increased slightly in noncore counties (+0.8%). In all county categories, preventable premature deaths from stroke decreased from 2010 to 2013, remained constant from 2013 to 2019, and then increased in 2020 at the start of the COVID-19 pandemic. Percentages of preventable premature deaths varied across states by urban-rural county classification during 2010-2022. During 2010-2022, nonmetropolitan counties had higher percentages of preventable premature deaths from the five leading causes of death than did metropolitan counties nationwide, across public health regions, and in most states. The gap between the most rural and most urban counties for preventable premature deaths increased during 2010-2022 for four causes of death (cancer, heart disease, CLRD, and stroke) and decreased for unintentional injury. Urban and suburban counties (large central metropolitan, large fringe metropolitan, medium metropolitan, and small metropolitan) experienced increases in preventable premature deaths from unintentional injury during 2010-2022, leading to a narrower gap between the already high (approximately 69% in 2022) percentage of preventable premature deaths in noncore and micropolitan counties. Sharp increases in preventable premature deaths from unintentional injury, heart disease, and stroke were observed in 2020, whereas preventable premature deaths from CLRD and cancer continued to decline. CLRD deaths decreased during 2017-2020 but increased in 2022. An increase in the percentage of preventable premature deaths for multiple leading causes of death was observed in 2020 and was likely associated with COVID-19-related conditions that contributed to increased mortality from heart disease and stroke. Routine tracking of preventable premature deaths based on urban-rural county classification might enable public health departments to identify and monitor geographic disparities in health outcomes. These disparities might be related to different levels of access to health care, social determinants of health, and other risk factors. Identifying areas with a high prevalence of potentially preventable mortality might be informative for interventions.

Environmental Justice and Systems Analysis for Air Quality Planning in the Port of Oakland in California.

Many frontline communities experience adverse health impacts from living in proximity to high-polluting industrial sources. Securing environmental justice requires, in part, a comprehensive set of quantitative indicators. We incorporate environmental justice and life-cycle thinking into air quality planning to assess fine particulate matter (PM2.5) exposure and monetized damages from operating and maintaining the Port of Oakland, a major multimodal marine port located in the historically marginalized West Oakland community in the San Francisco Bay Area. The exposure domain for the assessment is the entire San Francisco Bay Area, a home to more than 7.5 million people. Of the more than 14 sources included in the emissions inventory, emissions from large container ships, or ocean-going vessels (OGVs), dominate the PM2.5 intake, and supply chain sources (material production and delivery, fuel production) represent between 3.5% and 7.5% of annual intake. Exposure damages, which model the costs from excess mortalities resulting from exposure from the study's emission sources, range from USD 100 to 270 million per annum. Variations in damages are due to the use of different concentration-response relationships, hazard ratios, and Port resurfacing area assumptions. Racial and income-based exposure disparities are stark. The Black population and people within the lowest income quintile are 2.2 and 1.9 times more disproportionately exposed, respectively, to the Port's pollution sources relative to the general population. Mitigation efforts focused on electrifying in-port trucking operations yield modest reductions (3.5%) compared to strategies that prioritize emission reductions from OGVs and commercial harbor craft operations (8.7-55%). Our recommendations emphasize that a systems-based approach is critical for identifying all relevant emission sources and mitigation strategies for improving equity in civil infrastructure systems.

BENEFIT AND HARM OF ASPIRIN ON MORTALITY FROM GASTROINTESTINAL CANCERS VERSUS BLEEDING IN HELICOBACTER PYLORI-ERADICATED PATIENTS

We investigated benefit-risk profile of aspirin on mortality reduction from chemoprevention of gastrointestinal (GI) cancer versus excess mortality from bleeding among Helicobacter pylori (HP)-eradicated patients, and its interaction with proton pump inhibitors (PPIs). HP-eradicated patients (between 2003 and 2016), identified from a territory-wide database, were observed from date of HP therapy till death or end of study (July 2020). Primary exposure was aspirin use as time-varying variable. Primary outcome was GI cancer-related (gastrointestinal, hepatobiliary or pancreatic cancer) death and secondary outcome was bleeding-related (GIB or intracranial bleeding) death. Adjusted hazard ratio (aHR) of outcomes was calculated by multivariable Cox model after adjusting for age, sex, comorbidities and concomitant medications. Benefit-risk profile was expressed as adjusted absolute risk difference of cancer-related deaths and bleeding-related deaths between aspirin users and non-users. 87,967 subjects were followed for a median of 10.1years, with 1,294 (1.5%) GI cancer-related deaths and 304 (0.3%) bleeding-related deaths. Aspirin was associated with lower GI cancer-related mortality (aHR:0.51;95%CI:0.42-0.61), but higher bleeding-related mortality (aHR:1.52;95%CI:1.11-2.08). Among PPI users, aHR of bleeding-related mortality with aspirin was 1.06 (95%CI:0.70-1.63). For whole cohort, adjusted absolute risk difference between aspirin users and non-users was 7 (95%CI: 5-8) fewer cancer-related and 1 (95%CI: 0.3-3) more bleeding-related death per 10,000 person-years. Among concomitant PPI-aspirin use, there were 9 (95%CI:8-10) fewer cancer-related deaths per 10,000 person-years without increase in bleeding-related deaths. GI-cancer mortality benefit from aspirin outweighs bleeding-related mortality in HP-eradicated subjects, which is further enhanced by PPI use.

Artificial Intelligence Assessment of Biological Age from Transthoracic Echocardiography: Discrepancies to Chronologic Age Predict Significant Excess Mortality

Age and sex can be estimated by artificial intelligence based on various sources. We aimed to test whether convolutional neural networks could be trained to estimate the age and predict the sex using standard transthoracic echocardiography (TTE), and to evaluate its prognostic implications. The algorithm was trained on 76,342 patients, validated in 22,825 patients, and tested in 20,960 patients. It was then externally validated using data from a different hospital (N=556). Finally, a prospective cohort of handheld point-of-care ultrasound (POCUS) devices (N=319; ClinicalTrials.Gov NCT05455541) was used to confirm the findings. Multivariate Cox regression model was used to investigate the association between age-estimation and chronological age with overall survival. The mean average error in age estimation was 4.9 years, with a Pearson correlation coefficient of 0.922. The probabilistic value of sex had an overall accuracy of 96.1% and an area under the curve (AUC) of 0.993. External validation and prospective study cohorts yielded consistent results. Finally, survival analysis demonstrated that age prediction ≥ 5 years of chronological age was associated with an independent 34% increased risk of death during follow-up (p<0.001). Applying artificial intelligence to the standard TTE allows prediction of sex and estimation of age. Machine-based estimation is an independent predictor of overall survival and, with further evaluation, can be used for risk stratification and estimation of biological age.

An exploratory analysis of routine ferritin measurement upon admission and the prognostic implications of low-grade ferritinemia during inflammation

An exploratory analysis of routine ferritin measurement upon admission and the prognostic implications of low-grade ferritinemia during inflammation

B-29 | Examining Excess Mortality in Patients Presenting With Preeclampsia During the Covid-19 Pandemic: A National Inpatient Survey Analysis (2019-2020)

B-29 | Examining Excess Mortality in Patients Presenting With Preeclampsia During the Covid-19 Pandemic: A National Inpatient Survey Analysis (2019-2020)

Global, regional, and national burden of heatwave-related mortality from 1990 to 2019: A three-stage modelling study.

The regional disparity of heatwave-related mortality over a long period has not been sufficiently assessed across the globe, impeding the localisation of adaptation planning and risk management towards climate change. We quantified the global mortality burden associated with heatwaves at a spatial resolution of 0.5°×0.5° and the temporal change from 1990 to 2019. We collected data on daily deaths and temperature from 750 locations of 43 countries or regions, and 5 meta-predictors in 0.5°×0.5° resolution across the world. Heatwaves were defined as location-specific daily mean temperature ≥95th percentiles of year-round temperature range with duration ≥2 days. We first estimated the location-specific heatwave-mortality association. Secondly, a multivariate meta-regression was fitted between location-specific associations and 5 meta-predictors, which was in the third stage used with grid cell-specific meta-predictors to predict grid cell-specific association. Heatwave-related excess deaths were calculated for each grid and aggregated. During 1990 to 2019, 0.94% (95% CI: 0.68-1.19) of deaths [i.e., 153,078 cases (95% eCI: 109,950-194,227)] per warm season were estimated to be from heatwaves, accounting for 236 (95% eCI: 170-300) deaths per 10 million residents. The ratio between heatwave-related excess deaths and all premature deaths per warm season remained relatively unchanged over the 30 years, while the number of heatwave-related excess deaths per 10 million residents per warm season declined by 7.2% per decade in comparison to the 30-year average. Locations with the highest heatwave-related death ratio and rate were in Southern and Eastern Europe or areas had polar and alpine climates, and/or their residents had high incomes. The temporal change of heatwave-related mortality burden showed geographic disparities, such that locations with tropical climate or low incomes were observed with the greatest decline. The main limitation of this study was the lack of data from certain regions, e.g., Arabian Peninsula and South Asia. Heatwaves were associated with substantial mortality burden that varied spatiotemporally over the globe in the past 30 years. The findings indicate the potential benefit of governmental actions to enhance health sector adaptation and resilience, accounting for inequalities across communities.

In-Hospital Mortality in Patients with and without Dementia across Age Groups, Clinical Departments, and Primary Admission Diagnoses

Background: Studies have reported higher in-hospital mortality rates in patients living with dementia (PlwD) with limited evidence across age groups, clinical departments, and admission diagnoses. The aim of this study was to compare the in-hospital mortality rate of PlwD with patients without dementia across groups, clinical departments, and admission diagnoses. Methods: This case-control study included patients aged ≥ 60 years hospitalized in 1 of 14 German hospitals between January 2019 and July 2023. PlwD were matched to patients without dementia. The associations between dementia and in-hospital mortality across groups were assessed using univariable logistic regression analyses. Results: 15,956 patients with and 15,956 without dementia were included (mean age: 83.9 years, 60.7% female). PlwD had a significantly higher in-hospital mortality rate (14.0% vs. 11.7%; OR 1.24, 95% CI: 1.16–1.32) than non-dementia controls. The highest excess mortality rate was observed in the youngest age group (60–70 years: 10.9% vs. 5.7%; OR: 2.05, 95% CI: 1.30–3.24), decreased with age, and became non-significant in the oldest age group (≥90 years: 16.2% vs. 17.3%; OR: 0.93, 95% CI: 0.80–1.08). Significant differences were found for digestive system disorders (OR: 1.59; 95% CI: 1.15–1.89), cardiovascular and cerebrovascular disorders (OR: 1.51; 95% CI: 1.30–1.75), endocrine, nutritional, and metabolic diseases (OR: 1.42; 95% CI: 1.06–1.90), and pneumonia (OR: 1.20; 95% CI: 1.04–1.37), as well as for all clinic departments except for geriatric departments. Conclusion: The excess mortality rate was highest in younger age groups, where the general mortality and complication rate is relatively low in the general population. Appropriate approaches are needed, especially in non-geriatric wards.

Adverse Drug Reactions in Multimorbid Older People Exposed to Polypharmacy: Epidemiology and Prevention

Adverse drug reactions (ADRs) are frequent and represent a significant healthcare burden. ADRs are a potentially avoidable contributor to excess unscheduled hospital admissions, higher morbidity, mortality, and healthcare costs. The objective of this review is to examine the epidemiology of ADRs in older multimorbid adults and to explore strategies for ADR prevention. ADRs in this population are often linked to commonly prescribed medications, including anticoagulants, antiplatelet agents, insulin, and non-steroidal anti-inflammatory drugs, but ADRs and adverse drug events (ADEs) in fact encompass a much broader range of culprit drugs. Age-related factors such as changes in pharmacokinetics and pharmacodynamics, multimorbidity, polypharmacy, and frailty have been associated with ADR occurrences. Various strategies have been proposed to prevent ADRs in different clinical settings, such as structured routine medication review and the use of bespoke software applications to identify potentially inappropriate prescriptions and drug interactions. Although these approaches have demonstrated some improvement in the quality of prescribing, there is still a lack of consistent evidence regarding their effectiveness in preventing ADRs. The nuanced and often intricate complexities associated with older patients’ pharmacotherapy necessitate a comprehensive approach to attenuate the impact of ADRs within this growing section of most populations globally.