Excess Mortality Research Articles

The effect of the COVID-19 health disruptions on breast cancer mortality for older women: a semi-Markov modelling approach

ABSTRACT Public health measures necessitated by the COVID-19 pandemic have affected cancer pathways by halting screening, delaying diagnostic tests and reducing the numbers starting treatment. Specifically, this moves individuals from observed and treated pathways to unobserved and untreated pathways. We introduce a semi-Markov model that includes both, extending an industry-based multiple state model used for life and critical illness insurance. Our model includes events related to cancer diagnosis and progression based on publicly available population data for women aged 65–89 in England and on relevant medical literature. We quantify age-specific excess deaths, for a period up to 5 years, along with years of life expectancy lost and changes in cancer mortality by cancer stage. Our analysis suggests a 3–6% increase in breast cancer deaths, and a 4–6% increase in registrations of advanced breast cancer, robust under sensitivity analysis. This should be applicable to actuarial work in areas where longevity and advanced age morbidity affect healthcare, retirement and insurance.

Coronary Embolism Among Patients With ST-Segment-Elevation Myocardial Infarction and Atrial Fibrillation: An Underrecognized But Deadly Association.

The prevalence and impact of coronary emboli (CE) in patients with ST-segment-elevation myocardial infarction (STEMI) and atrial fibrillation (AF) have not been specifically studied. The objective was to describe the clinical characteristics and outcomes of patients with AF and CE in a large series of patients with STEMI. We investigated 2292 consecutive patients with STEMI and among them 225 patients with AF: 46 patients with a STEMI related to CE (group A) and 179 patients with a STEMI related to an atherosclerotic cause (group B). Compared with the 2067 patients without AF and CE (group C), patients with AF and CE were older (73 versus 59 years, P<0.05), more likely to be female (43% versus 22%, P<0.05), and presented more frequently with cardiogenic shock at admission (26% versus 9%, P<0.05). The baseline characteristics of patients with AF (group A versus B) did not differ significantly according to STEMI pathogenesis. In the unadjusted analysis, the 45-day mortality was higher in patients with CE and AF (group A versus group C: 20% versus 4%; P<0.05 and group A versus group B: 20% versus 8%, P=not significant); this trend persisted at 2-year follow-up (group A versus group C: 24% versus 6%; P<0.05 and group A versus group B: 24% versus 17%, P=not significant). After stabilized inverse exposure probability weighting adjustment, a higher 45-day mortality rate was confirmed in patients with CE and AF (group A versus group C: 18% versus 5%, P<0.05). In patients presenting with STEMI and AF, CE was associated with excess early mortality. URL: clinicaltrials.gov. Identifier: NCT05679843.

Longitudinal analysis of nursing home residents' T cell responses after SARS-CoV-2 mRNA vaccinations shows influence of biological sex and SARS-CoV-2 infection history.

Vaccines and vaccine boosting have blunted excess morbidity and mortality from SARS-CoV-2 infection suffered by older nursing home residents (NHR). However, the impact of repeated vaccination on the T cell response based on biological sex and prior infection of NHR remain understudied. We examined T cell responses to mRNA vaccines to SARS-CoV-2 in a cohort of NHR and healthcare workers (HCW) over 2 years. We used IFN-γ ELIspot and flow cytometry to assess T cell response before, two weeks and 6 months after the initial series and each of two booster vaccines. We analyzed these data longitudinally with mixed-effect modeling and also examined subsets of our cohorts for additional changes in T cell effector function. We show that prior SARS-CoV-2 infection and female sex contribute to higher T cell response in NHR but not HCW. When looking across time points, NHR but not HCW with prior infection had significantly higher T cell responses than infection-naive subjects. These patterns of response were maintained across multiple booster vaccinations and suggest that the age, multimorbidity, and/or frailty of the NHR cohort may accentuate sex and infection status differences in T cell response to mRNA vaccination.

An evaluation of the impact of social and structural determinants of health on forgone care during the COVID-19 pandemic in Baltimore, Maryland.

Evidence suggests that reductions in healthcare utilization, including forgone care, during the COVID-19 pandemic may be contributing towards excess morbidity and mortality. The objective of this study was to describe individual and community-level correlates of forgone care during the COVID-19 pandemic. We conducted a cross-sectional, secondary data analysis of participants (n = 2,003) who reported needing healthcare in two population-representative surveys conducted in Baltimore, MD in 2021 and 2021-2022. Abstracted data included the experience of forgone care, socio-demographic data, comorbidities, financial strain, and community of residence. Participant's community of residence were linked with data acquired from the Baltimore Neighborhood Indicators Alliance relevant to healthcare access and utilization, including walkability and internet access, among others. The data were analyzed using weighted random effects logistic regression. Individual-level factors found to be associated with increased odds for forgone care included individuals age 35-49 (compared to 18-34), female sex, experiencing housing insecurity during the pandemic, and the presence of functional limitations and mental illness. Black/African American individuals were found to have reduced odds of forgone care, compared to any other race. No community-level factors were significant in the multilevel analyses. Moving forward, it will be critical that health systems identify ways to address any barriers to care that populations might be experiencing, such as the use of mobile health services or telemedicine platforms. Additionally, public health emergency preparedness planning efforts must account for the unique needs of communities during future crises, to ensure that their health needs can continue to be met. Finally, additional research is needed to better understand how healthcare access and utilization practices have changed during versus before the pandemic.

Diabetes-related risk factors and survival among individuals with type 2 diabetes and breast, lung, colorectal, or prostate cancer

Premature death in diabetes is increasingly caused by cancer. The objectives were to estimate the excess mortality when individuals with type 2 diabetes(T2D) were diagnosed with cancer, and to examine the impact of modifiable diabetes-related risk factors. This longitudinal nationwide cohort study included individuals with T2D registered in the Swedish National Diabetes Register between 1998–2019. Poisson models were used to estimate mortality as a function of time-updated risk-factors, adjusted for sex, age, diabetes duration, marital status, country of birth, BMI, blood pressure, lipids, albuminuria, smoking, and physical activity. We included 690,539 individuals with T2D and during 4,787,326 person-years of follow-up 179,627 individuals died. Overall, the all-cause mortality rate ratio was 3.75 [95%confidence interval(CI):3.69–3.81] for individuals with T2D and cancer compared to those remaining free of cancer. The most marked risk factors associated to mortality among individuals with T2D and cancer were low physical activity, 1.59 (1.57–1.61) and smoking, 2.15 (2.08–2.22), whereas HbA1c, lipids, hypertension, and BMI had no/weak associations with survival. In a future with more patients with comorbid T2D and cancer diagnoses, these results suggest that smoking and physical activity might be the two most salient modifiable risk factors for mortality in people with type 2 diabetes and cancer.

Plasma Biomarkers for Hypertension-Mediated Organ Damage Detection: A Narrative Review

Hypertension (HT) is a disease that poses a serious threat to human health, mediating organ damage such as the cardiovascular (CV) system, kidneys, central nervous system (CNS), and retinae, ultimately increasing the risk of death due to damage to the entire vascular system. Thus, the widespread prevalence of hypertension brings enormous health problems and socioeconomic burdens worldwide. The goal of hypertension management is to prevent the risk of hypertension-mediated organ damage and excess mortality of cardiovascular diseases. To achieve this goal, hypertension guidelines recommend accurate monitoring of blood pressure and assessment of associated target organ damage. Early identification of organ damage mediated by hypertension is therefore crucial. Plasma biomarkers as a non-invasive test can help identify patients with organ damage mediated by hypertension who will benefit from antihypertensive treatment optimization and improved prognosis. In this review, we provide an overview of some currently available, under-researched, potential plasma biomarkers of organ damage mediated by hypertension, looking for biomarkers that can be detected by simple testing to identify hypertensive patients with organ damage, which is of great significance in clinical work. Natriuretic peptides (NPs) can be utilized as a traditional biomarker to detect hypertension-mediated organ damage, especially for heart failure. Nevertheless, we additionally may need to combine two or more plasma biomarkers to monitor organ damage in the early stages of hypertension.

Evaluating the temperature–mortality relationship over 16 years in Cyprus

ABSTRACT In many regions of the world, the relationship between ambient temperature and mortality is well-documented, but little is known about Cyprus, a Mediterranean island country where climate change is progressing faster than the global average. We Examined the association between daily ambient temperature and all-cause mortality risk in Cyprus. We conducted a time-series analysis with quasipoisson distribution and distributed lag non-linear models to investigate the association between temperature and all-cause mortality from 1 January 2004 to 31 December 2019 in five districts in Cyprus. We then performed a meta-analysis to estimate the overall temperature-mortality dose-response relationship in Cyprus. Excess mortality was computed to determine the public health burden caused by extreme temperatures. We did not find evidence of heterogeneity between the five districts (p = 0.47). The pooled results show that for cold effects, comparing the 1st, 2.5th, and 5th percentiles to the optimal temperature (temperature associated with least mortality, 25 ℃), the overall relative risks of mortality were 1.55 (95% CI: 1.32, 1.82), 1.41 (95% CI: 1.21, 1.64), and 1.32 (95% CI: 1.15, 1.52), respectively. For heat effects, the overall relative risks of mortality at the 95th, 97.5th and 99th percentiles were 1.10 (95% CI: 1.04, 1.16), 1.17 (95% CI: 1.07, 1.29), and 1.29 (95% CI: 1.11, 1.5), respectively. The excess mortality attributable to cold days accounted for 8.0 deaths (95% empirical CI: 4.5–10.8) for every 100 deaths, while the excess mortality attributable to heat days accounted for 1.3 deaths (95% empirical CI: 0.7–1.7) for every 100 deaths. The results prompt additional research into environmental risk prevention in this under-studied hot and dry region that could experience disproportionate climate change related exposures. Implications: The quantification of excess mortality attributable to temperature extremes shows an urgent need for targeted public health interventions and climate adaptation strategies in Cyprus and similar regions facing rapid climate change. Future steps should look into subpopulation sensitivity, coping strategies, and adaptive interventions to reduce potential future risks.

Were the 2022 Summer Heatwaves a Strong Cause of Europe’s Excess Deaths?

During the 2022 summer, Europe experienced heatwaves with record temperatures, and a study has argued that they caused about 62,000 deaths between 30 May and 4 September. The total number of excess deaths during the same period was about 137,000, indicating that the heatwaves were a substantial contributor. Not ruling out that explanation entirely, this paper argues that it was unlikely a strong cause. First, if the heatwaves were a strong cause of numerous deaths, one would assume that the older and deprived were relatively likely to die. However, during the 2022 summer heatwaves in England, which were claimed to have caused about 2900 deaths, the oldest age cohort did not have a higher excess death rate than the middle age cohort, and the excess death rate actually decreased with deprivation status. Moreover, Iceland had among Europe’s highest excess death rates during the summer, which cannot be attributed to heatwaves. During June, July, and August 2022, comparable southern hemisphere countries furthermore had high excess death rates, which cannot be attributed to heatwaves either, as it was during their winter. Also, Europe’s excess death rate was higher during the 2022–2023 winter than during the 2022 summer, and intuitively not attributed to heatwaves, but neither to cold weather, as that winter was abnormally mild. Finally, the paper discusses the puzzling issue that about 56% more women than men, relative to the population, presumably died from the heatwaves.

V-A ECMO window of opportunity: identification of potential responders after an acute myocardial infarction complicated by cardiogenic shock

Abstract Funding Acknowledgements None. Background V-A ECMO is designed to supply oxygen demands in patients with circulatory failure. Neutral results obtained in recent cardiogenic shock (CS) trials are probably related to the inclusion of a high proportion of patients with SCAI C stage, in many of whom, the device might not provide hemodynamic benefit despite the addition of inherent complications. Mechanical circulatory support could potentially have a role only for patients in SCAI D-E stages. Purpose Our aim was to explore the excess in mortality explained by a SCAI D-E stage at 12h, compared to a SCAI A-C stages at 12h, in patients admitted due to an acute myocardial infarction (AMI) complicated by CS (stages C-E at admission). Additionally, we aimed to identify those factors at admission—clinical, electrocardiographic, gasometrical, echocardiographic, and angiographic—which predict whether a patient will progress to SCAI D-E stages within the subsequent 12h from CS onset. Main Outcome: SCAI D and E stage at 12h. Methods We retrospectively analysed those patients admitted due to an AMI in SCAI C-E stages at admission, that had been prospectively screened for EUROSHOCK trial. We classified the patients in two groups: "SCAI A-C" and "SCAI D-E" at 12 hours and conducted a survival analysis. Additionally, we conducted a univariate and multivariate analysis including arrival potential predictors for SCAI D-E at 12 hours. Results A total of 72 patients were included. At admission 25 patien were in SCAI D-E. At 12 hours, 42 patients were in SCAI D-E, and this group showed a higher 30-day mortality rate particularly explained by an excess of mortality within the first 7 days (Figure 1). There were no significant differences between groups in most baseline characteristics (Table 1) such as age or gender. We observed a fewer proportion of previous chronic treatment with negative inotropes (betablockers and calcium channel antagonists) in the SCAI D-E group. Overall, anterior ST elevation on EKG was more prevalent among SCAI D-E group, median pH lower and median glycaemia and lactate higher. In the multivariate analysis after adjustment by confounders, the independently predictors at arrival for the development of a SCAI D-E stage at 12h were culprit LAD, cardiac arrest in the cath Lab, low initial median pH and final TIMI &amp;lt;3 result. Conclusions In a cohort of AMI patients complicated by CS, those patients who remained in a SCAI D-E stage at 12 hours from CS onset, compared to those in A-C, showed a 26% excess mortality at 30-day follow-up, especially during the first week. Patients who presented with LAD as the culprit artery, low initial pH, cardiac arrest in the cath lab, and got a TIMI &amp;lt;3 result after PCI were independently associated with the development of SCAI D-E within 12 hours from admission. Patients meeting these criteria could benefit from early selective mechanical support and be taken into consideration in the design of future randomized controlled trials.

Persistent high mortality rates for Diabetes Mellitus and Hypertension after excluding deaths associated with COVID-19 in Brazil, 2020-2022.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a significant public health challenge globally, with Brazil being no exception. Excess mortality during this period reached alarming levels. Cardiovascular diseases (CVD), Systemic Hypertension (HTN), and Diabetes Mellitus (DM) were associated with increased mortality. However, the specific impact of DM and HTN on mortality during the pandemic remains poorly understood. This study analyzed mortality data from Brazil's mortality system, covering the period from 2015 to 2022. Data included all causes of death as listed on death certificates, categorized by International Classification of Diseases 10th edition (ICD-10) codes. Population data were obtained from the Brazilian Census. Mortality ratios (MRs) were calculated by comparing death rates in 2020, 2021, and 2022 to the average rates from 2015 to 2019. Adjusted MRs were calculated using Poisson models. Between 2015 and 2022, Brazil recorded a total of 11,423,288 deaths. Death rates remained relatively stable until 2019 but experienced a sharp increase in 2020 and 2021. In 2022, although a decrease was observed, it did not return to pre-pandemic levels. This trend persisted even when analyzing records mentioning DM, HTN, or CVD. Excluding death certificates mentioning COVID-19 codes, the trends still showed increases from 2020 through 2022, though less pronounced. This study highlights the persistent high mortality rates for DM and HTN in Brazil during the years 2020-2022, even after excluding deaths associated with COVID-19. These findings emphasize the need for continued attention to managing and preventing DM and HTN as part of public health strategies, both during and beyond the COVID-19 pandemic. There are complex interactions between these conditions and the pandemic's impact on mortality rates.

Reduced temporal muscle thickness predicts shorter survival in patients undergoing chronic subdural haematoma drainage.

Chronic subdural haematoma (CSDH) drainage is a common neurosurgical procedure. CSDHs cause excess mortality, which is exacerbated by frailty. Sarcopenia contributes to frailty - its key component, low muscle mass, can be assessed using cross-sectional imaging. We aimed to examine the prognostic role of temporal muscle thickness (TMT) measured from preoperative computed tomography head scans among patients undergoing surgical CSDH drainage. We retrospectively identified all patients who underwent CSDH drainage within 1year of February 2019. We measured their mean TMT from preoperative computed tomography scans, tested the reliability of these measurements, and evaluated their prognostic value for postoperative survival. One hundred and eighty-eight (122, 65% males) patients (median age 78years, IQR 70-85years) were included. Thirty-four (18%) patients died within 2years, and 51 (27%) died at a median follow-up of 39months (IQR 34-42months). Intra- and inter-observer reliability of TMT measurements was good-to-excellent (ICC 0.85-0.97, P<0.05). TMT decreased with age (Pearson's r=-0.38, P<0.001). Females had lower TMT than males (P<0.001). The optimal TMT cut-off values for predicting two-year survival were 4.475mm for males and 3.125mm for females. TMT below these cut-offs was associated with shorter survival in both univariate (HR 3.24, 95% CI 1.85-5.67) and multivariate (HR 1.86, 95% CI 1.02-3.36) analyses adjusted for age, ASA grade and bleed size. The effect of TMT on mortality was not mediated by age. In patients with CSDH, TMT measurements from preoperative imaging were reliable and contained prognostic information supplemental to previously known predictors of poor outcomes.

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.