Specific Deaths Research Articles

Unravelling COVID-19 social mortality patterns using conditional inference tree algorithm

Abstract Background The COVID-19 pandemic led to significant excess mortality in 2020 in Belgium. By using microlevel cause-specific mortality data for the total Belgian adult population in 2020, three outcomes were considered in this study aiming at predicting sociodemographic (SD) and socioeconomic (SE) patterns of 1) COVID-19 specific death compared to survival; 2) all other causes of death (OCOD) compared to survival; 3) COVID-19 specific deaths compared to all OCOD. Methods Multivariable logistic regression models were fitted for the three outcomes. In addition, we computed conditional inference tree (CIT) algorithms, complementing regression models, to identify and rank the strongest SD and SE predictors of the three outcomes. Results Older people, males, people living in collectivities, first-generation migrants, and deprived SE groups experienced higher odds of dying from COVID-19 compared to survival; living in collectivities was identified by the CIT as the strongest predictor followed by age and sex. Education emerged as one of the strongest predictors for people not living in collectivities. Overall, similar patterns were observed for all OCOD except for first- and second-generation migrants having lower odds of all OCOD compared to survival; age group was identified by the CIT as the strongest predictor. Older people, males, people living in collectivities, first- and second-generation migrants, and people with lower levels of education had higher odds of COVID-19 death compared to all OCOD; living in collectivities was identified by the CIT as the strongest predictor followed by age, sex, and migration status. Education and income emerged as the strongest predictors among people not living in collectivities. Conclusions This study identified important SD and SE disparities in COVID-19 mortality underlying the importance of implementing preventive measures, particularly within the most vulnerable populations, in infectious disease pandemic preparedness. Key messages • Living in collectivities appeared to be the strongest predictor of COVID-19 death across all age groups, highlighting the importance of preventive measures in reducing the transmission of the virus. • Poor education plays a crucial role in predicting COVID-19 death among people not living in collectivities, highlighting the importance of targeting preventive measures towards low educated groups.

PDOC-05 MULTIPLE ISOCENTRE VMAT PLANNING FOR PAEDIATRIC CRANIOSPINAL IRRADIATION USING THE HALCYON LINEAR ACCELERATOR

Abstract Paediatric brain tumours constitute the leading cause of cancer specific deaths worldwide. Many patients require craniospinal irradiation (CSI), one of the most technically demanding techniques in radiotherapy. Many LMIC centres have installed Varian Halcyon® linear accelerators and require a technique to execute CSI safely. This study evaluates a multiple isocentre VMAT planning strategy for CSI. The Halcyon is a ring based linac with a single 6MV flattening filter free (FFF) photon beam, a stacked and staggered double MLC for beam shaping and modulation, and no movable collimator jaws. Multiple isocentres are required for treatment fields longer than 28 cm. Paediatric CSI requires dose to be delivered to the entire thecal sac incorporating whole brain as well as entire spinal cord, resulting in long planning target volumes. In addition to the length of the treatment field, CSI treatments are complex due to the change in geometry of the target and the patient body over the length of the treatment field. Traditional 3D conformal radiotherapy techniques (3DCRT) require multiple isocentres with field matching and junction feathering. VMAT offers an alternative, but also require multiple fields to achieve coverage. A Halcyon based three isocentre VMAT technique was investigated and evaluated according to the QUANTEC criteria. Portal dosimetry quality assurance was performed on all fields to ensure they were clinically deliverable. High quality paediatric CSI VMAT treatments can be delivered on the Halcyon, using three isocentres with automatic feathering applied in field overlap regions. Two full arcs and one support arc were used for the brain area, with two posterior partial arcs per spine isocentre, each covering a total of 140 degrees posteriorly to limit integral dose and dose to the lungs and kidneys. Imaging and setup is required for every isocentre further than 8cm/10cm (Halcyon V2/V3 respectively) from the previous isocentre.

Maroon Anti-necropolitics

This article describes Maroon anti-necropolitics and its implications for multispecies justice to aid in creating a genuinely decolonial Caribbean ecological theory. Ndyuka Maroons, the descendants of one nation of self-liberated formerly enslaved Black Surinamese peoples, have created a cosmopolitical order based on the refusal of necropolitics (which is the assumption that politics must be predicated on the sovereign human appropriation of the right to kill or let die). In its place, Ndyukas practice an ethics of sociality premised on the shared collective vulnerability of present and future generations to the consequences of acts of killing. This Maroon anti-necropolitics has three primary principles: (1) death always relates specific deaths to future collective harm; (2) humans do not have a sovereign right to death over the lives of others; and (3) death does not rupture relations between the living and the dead, or the community and its enemies, but intensifies them by imposing ineradicable connections of tragic loss between perpetrators and victims. Ndyukas accordingly articulate a theory of relational justice that rejects human sovereignty while emphasizing human responsibility. This article illustrates how Maroons have imagined a world beyond necropolitics and why this helps confront the ways in which necropolitical assumptions inflect how multispecies justice is imagined.

Identification of patients at high risk for relapse using the Merlin Assay (CP-GEP) in an independent cohort of 451 patients (pts) with stage I/II melanoma who did not undergo sentinel lymph node biopsy.

9574 Background: Sentinel lymph node biopsy (SLNB) is the gold standard for nodal assessment in staging cutaneous melanoma (CM) according to AJCC v8 guideline. 80-85% of pts are negative for nodal metastasis, but most pts who relapse or die from melanoma are initially diagnosed as ‘low risk’ early-stage. Previously we showed that the clinicopathological-gene expression profiling (CP-GEP) model is able to stratify SLNB negative pts for their risk of recurrence (1). Later we showed in a small cohort (n=80) that CP-GEP also has the potential to stratify pts who did not undergo SLNB in low and high-risk of recurrence (2). Here we investigate CP-GEP ability to stratify pts who did not undergo SLNB for their risk of recurrence in an expanded cohort. Methods: We analysedformalin-fixed paraffin-embedded primary tumor samples of 451 pts with stage I/II CM diagnosed between 2000-2017, included in the Central Malignant Melanoma Registry, who did not receive SLNB. Study hypothesis and protocol were prospectively formulated. Tumors were analyzed blinded to clinical outcome. The CP-GEP model used combines the expression of 8 genes ( SERPINE2, GDF15, ITGB3, CXCL8, LOXL4, TGFBR1, PLAT and MLANA) by quantitative reverse transcription polymerase chain reaction with age and Breslow thickness to obtain a binary output: CP-GEP Low- or High-Risk. Relapse-free survival (RFS), distant metastasis free survival (DMFS) and Melanoma Specific Survival (MSS) were evaluated using Kaplan-Meier curves. Results: We included 451 pts (stage IA-IIC). 40% were females, median age was 63-year-old, median Breslow thickness was 0.5 mm, and the majority were not ulcerated (96%). An interim analysis was performed on samples from 159 pts and showed the following survival: 5-year RFS 85.8%; DMFS 94.1; MSS 95.7%. The median follow-up time of 57 months (RFS). CP-GEP identified 149 pts as Low-Risk and 10 pts as High-Risk. The 5-year RFS rate was 90.5% and 0% (HR 23.85; p < 0.001), 5-year DMFS was 97.2% and 27% (HR 43.14; p < 0.001), respectively for CP-GEP Low-Risk and High-Risk pts. The 5-year MSS was 99.1% for Low-Risk pts and 25.7% for High-Risk patients (HR 112.96; p < 0.001), capturing 4 out of 5 melanoma specific deaths in the CP-GEP High-Risk group. The final survival analysis of the whole cohort will be presented at the congress. Conclusions: This study shows that CP-GEP has the potential to stratify pts with early-stage melanoma who did not undergo SLNB based on their risk of recurrence. Pts with CP-GEP Low-Risk have a good long-term survival. Contrary, pts with CP-GEP High-Risk have a high risk of recurrence. CP-GEP may have the potential to stratify pts beyond SLNB. 1. Amaral et al, ASCO 2022. 2. Amaral et al, EJC 2023.

Abstract 3425: Genetic predisposition to obesity and survival in women with breast cancer

Abstract Background. Higher body mass index (BMI) is associated with poor survival after breast cancer diagnosis. BMI is a heritable trait. A polygenic risk score (PRS) for BMI has been associated with cardiometabolic traits and found to modify weight loss interventions. Whether BMI genetic scores affect survival in women with breast cancer is unknown. Methods. This analysis was conducted in the Cancer Prevention Study II Nutrition cohort. Women diagnosed with non-metastatic breast cancer between 1992 and 2017 were included in the analysis if they had genotype data. Analyses were restricted to unrelated, postmenopausal women at the time of diagnosis who were of European ancestry (N=3,566). Deaths through 2020 were identified through linkage with the National Death Index. Primary cause of death was based on the International Classification of Disease codes. Pre-diagnosis BMI was self-reported (median 1.3 years from BMI measurement to diagnosis, interquartile range (IQR): 0.6, 1.9). We constructed a PRS using findings from a published meta-analysis of BMI genome wide association studies (GWAS) that included ~700,000 individuals and the PRSice tool.Hazard ratios (HR) and 95% confidence intervals (CI) between the PRS and all-cause mortality were estimated using Cox proportional hazards regression and Fine and Gray models for cause-specific mortality to account for competing risks. Models were adjusted for age and GWAS-specific statistically significant (P<0.05) principal components for population stratification. Mediation was estimated using the mediation R package. Results. The median age at diagnosis was 71.5 years (IQR: 66.3, 76.8). Most women were overweight (33.5%) or obese (18.4%) and were diagnosed with localized stage (63%) and estrogen receptor positive (65%) breast cancer. During a median follow-up of 14.5 years (IQR: 9.7-19.8), there were 1,825 (51.2%) deaths, including 301 breast cancer and 337 cardiovascular disease (CVD) specific deaths. In multivariable models, a 5 Kg/m2 increase in BMI was associated with increased risks of all-cause mortality (HR=1.09, 95% CI: 1.04, 1.15), breast cancer-specific mortality (HR=1.27, 95% CI: 1.13, 1.42), and CVD-specific mortality (HR=1.25, 95% CI: 1.11, 1.41). The PRS was highly predictive of pre-diagnostic BMI (P<0.001). A 1-standard deviation increase in the PRS was associated with statistically increased risk of all-cause mortality (HR=1.06, 95% CI: 1.02, 1.11). Risks of breast cancer (HR=1.07, 95% CI: 0.96, 1.19) or CVD (HR=1.01, 95% CI: 0.90, 1.12) specific mortality did not reach statistical significance. We estimated that 27% of the PRS and all-cause mortality association was mediated by BMI (95% CI: 12%, 91%; P=0.004). Conclusions. Women with breast cancer predisposed to higher BMI were at increased risk of all-cause mortality. A BMI-related PRS may be a useful tool to identify women with breast cancer in need of additional interventions and/or surveillance. Citation Format: Clara Bodelon, Adriana Lori, Mariah Landry, James Hodge, Parichoy Pal Choudhury, Ying Wang, Lauren E. McCullough, Alpa V. Patel, Lauren R. Teras. Genetic predisposition to obesity and survival in women with breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3425.

Changes in tuberculosis burden and its associated risk factors in Guizhou Province of China during 2006–2020: an observational study

BackgroundUnderstanding the trends of tuberculosis (TB) burden and its risk factors at the provincial level in the context of global End TB targets is crucial to identify the progress and challenges in TB control. We aimed to estimate the burden of TB and risk factors for death from 2006 to 2020 for the first time in Guizhou Province, China.MethodsData were collected from the national TB surveillance system. Four indicators of TB burden and their corresponding age-standardized rates (ASRs), including incidence (ASIR), prevalence (ASPR), mortality (ASMR) and disability-adjusted life years (DALYs) (ASDR), were estimated and stratified by year, age, gender and prefecture. Temporal trends of ASRs were presented by locally weighted regression, and the annual percentage change was calculated. The correlation between gross domestic product (GDP) per capita and ASRs was evaluated by Pearson correlation analysis. The associated risk factors for death in PTB patients were determined using logistic regression models.ResultsA total of 557,476 pulmonary TB (PTB) cases and 11,234 deaths were reported, including 2233 (19.9%) TB specific deaths and 9001 (80.1%) deaths from other causes. The 15-year average incidence, prevalence and mortality rates were 94.6, 102.6 and 2.1 per 100,000 population, respectively. The average DALY rate was 0.60 per 1000 population. The ASIR and ASPR have shown downward trends since 2012, with the largest percentage decrease in 2020 (ASIR: -29.8%; ASPR: -30.5%). The number in TB specific deaths consistently decreased during the study period (P<0.001), while the increase in deaths from other causes drove the overall upward trend in ASMR and ASDR. Four ASRs remained high in males and 5 prefectures. GDP per capita was negatively associated with the ASIR, ASPR and ASDR (P<0.05). Among PTB patients, men, patients with no fixed job, those with a low GDP level, patients with increasing age, those previously treated, those with severe symptoms, those transferred in and those receiving directly observed treatment were more likely to suffer death.ConclusionGuizhou has made progress in reducing PTB cases and TB specific deaths over the last 15 years. Targeted interventions are needed to address these risk factors for death in PTB patients and high-risk areas.

Perinatal depression and risk of mortality: nationwide, register based study in Sweden

ObjectiveTo determine whether women with perinatal depression are at an increased risk of death compared with women who did not develop the disorder, and compared with full sisters.DesignNationwide, register based...

Abstract IA047: A multiomic approach towards identifying actionable targets to combat prostate cancer health disparities

Abstract Prostate cancer (PC) is the most commonly diagnosed cancer among African American men (AA) and continues to be the largest difference in absolute incidence and cancer specific deaths between AA and Caucasian men (CA). AA have a 70% higher incidence of PC than CA and over a 2 times higher mortality rate. Among men undergoing prostate biopsy In an equal access setting (i.e. the VA), AA are ~50% more likely to have PC and ~80% more likely to have high-grade PC than CA. The frequency of PC associated genetic alterations and differences in oncogene expression in PCs is altered from CA and AA. While social economic status and environmental factors may play a role in PC health disparities, there are inherent genetic/molecular differences that account for the differences in PC outcomes between CA and AA. We sought to test our hypothesis that there is subset of actionable gene products that are essential for enhanced PC progression in AA. A focused and clinically informed CRISPR knockout screen was conducted to identify and functionally validate race specific actionable genes that contribute to the increased risks of fatal PC in AA. The CRISPR screen was designed leveraging a radical prostatectomy trancscriptomic dataset from the Durham VA Medical Center that was linked with long-term clinical outcome data. This unique dataset consists of ~600-profiled radical prostatectomy samples of which over 50% were from AA patients. A cox hazard analysis revealed differentially expressed genes (DEGs) which positively associated with increased risk of metastatic disease unique to AA PC patients. To identify drug targetable genes, these DEGs were filtered against the drug gene interaction database (DGIdb).This approach yielded 89 genes positively associated with increased risk of metastatic outcome in AA and 236 genes in CA only. The CRISPR KO screen resulted in 19 genes significantly depleted genes. Of these 19 hits, 11 genes were genes associated with metastasis in AA, while 8 hits were CA genes, with 5 of 11 AA hits have documented small molecule inhibitors. To further prioritize our hits, we have conducted spatial transcriptomic analysis of radical prostatectomy tissues from AA and CA PCs. By standard H and E staining these tumors looking quite similar. But spatial analysis of AA compared to CA tissues revealed differences in immune cells and cells associated with tumor microenvironment. These integative multiomic approach reveals new cell identities that may contribute to the aggressive pathogenicity of PC in AA compared to CA. CRISPR models and small molecule inhibitors of our top candidates will be used in investigate druggability of these DEGs. This study lays the groundwork for potential therapeutics targeted towards PC in AA men. Citation Format: Felipe Dezem, Aiza Akhtar, Sungyong You, So Young Kim, Jasmine Plummer, Everardo Macias. A multiomic approach towards identifying actionable targets to combat prostate cancer health disparities [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr IA047.

Air pollution deaths attributable to fossil fuels: observational and modelling study

ObjectivesTo estimate all cause and cause specific deaths that are attributable to fossil fuel related air pollution and to assess potential health benefits from policies that replace fossil fuels with...

Reduced lung function and cause-specific mortality: A population-based study of Norwegian men followed for 26 years

Background and aimReduced lung function is associated with increased mortality, but it is unclear how different spirometric patterns are related to specific deaths. Aim of this study was to investigate these associations in a large general population cohort. MethodsThe study population consisted of 26,091 men aged 30–46 years from the Pneumoconiosis Survey of Western Norway conducted in 1988–1990 with follow-up on date and cause of death for 26 years. Cox proportional hazard models were used to estimate the association between baseline FEV1, FVC, obstructive (OSP) and restrictive spirometric pattern (RSP) (z-scores calculated according to GLI-2012 equations) and mortality (European 2012 shortlist classification (E−2012)), after adjustment for age, body mass index, smoking habits, and education. ResultsIn total, 2462 (9%) subjects died. A predominant reduction of FEV1 (and OSP) were associated with respiratory non-cancer (E−8) (HR for one unit FEV1 z-score decrease 2.29 (95% CI 1.90, 2.77) and lung cancer mortality (E−2.1.8) (1.27(1.12, 1.44)). A similar reduction of FEV1 and FVC (and RSP) were associated with diabetes (E−4.1) (FEV1 2.21(1.67, 2.92), FVC 2.41(1.75, 3.32)), cerebrovascular (E−7.3) (1.52(1.21, 1.91), 1.54(1.19, 1.98)), ischemic heart disease (E−7.1) (1.22(1.10, 1.35), 1.21(1.08, 1.36)), neurological (E−6.3) (1.56(1.21, 2.01), 1.61(1.22, 2.13)), suicide (E−17.2) (1.37(1.13, 1.65), 1.29(1.04, 1.59)) and hematological cancer mortality (E−2.1.19–21) (1.29(1.05, 1.58), (1.26(1.00, 1.58)). No association was found between reduced lung function and mortality due to accidents, alcohol abuse, digestive and genitourinary cancer. ConclusionsSpirometric obstruction was mainly related to pulmonary mortality. Spirometric restriction was mainly related to extra-pulmonary mortality.

The quality of media reporting of suicide news in a high suicide state of India against World Health Organization guidelines: A content analysis study of major newspapers in Chhattisgarh

ObjectivesSuicide rates in India are amongst the highest in the world, resulting in an estimated 250,000 suicide deaths annually, and suicide rates in the state of Chhattisgarh are more than double the national average. Responsible media reporting is one of the few population-level suicide prevention interventions. To inform media interventions, the objective of our study was to assess the quality of newspaper reporting of suicide-related news in Chhattisgarh against World Health Organization (WHO) suicide reporting guidelines. MethodsWe used content analysis to assess the quality of suicide reporting against WHO guidelines in the thirteen most highly read Hindi- and English-language daily newspapers in Chhattisgarh between February and July of 2019. ResultsA total of 441 suicide articles were retrieved. The mean number of suicide articles per day per newspaper was 0.6 (range 0.2–1.1) and 33.3% of the articles were 10 sentences or less. The vast majority (97.8%) of articles primarily focused on reporting of specific suicide deaths and attempts. Harmful reporting practices were very common (for example, a detailed suicide method was reported in 38.7% of articles) while helpful reporting practices were rare (for example, just 0.5% gave contact details for a suicide support service). ConclusionsWe observed that short and explicit articles covering suicide incidents was commonplace amongst newspapers in Chhattisgarh. Attempts should be made to devise context-specific strategies to boost the positive contribution that media can make to suicide prevention in Chhattisgarh.

Influence of the Hypersensitivity to Low Dose Phenomenon on the Tumor Response to Hypofractionated Stereotactic Body Radiation Therapy.

Stereotactic body radiation therapy (SBRT) has made the hypofractionation of high doses delivered in a few sessions more acceptable. While the benefits of hypofractionated SBRT have been attributed to additional vascular, immune effects, or specific cell deaths, a radiobiological and mechanistic model is still needed. By considering each session of SBRT, the dose is divided into hundreds of minibeams delivering some fractions of Gy. In such a dose range, the hypersensitivity to low dose (HRS) phenomenon can occur. HRS produces a biological effect equivalent to that produced by a dose 5-to-10 times higher. To examine whether HRS could contribute to enhancing radiation effects under SBRT conditions, we exposed tumor cells of different HRS statuses to SBRT. Four human HRS-positive and two HRS-negative tumor cell lines were exposed to different dose delivery modes: a single dose of 0.2 Gy, 2 Gy, 10 × 0.2 Gy, and a single dose of 2 Gy using a non-coplanar isocentric minibeams irradiation mode were delivered. Anti-γH2AX immunofluorescence, assessing DNA double-strand breaks (DSB), was applied. In the HRS-positive cells, the DSB produced by 10 × 0.2 Gy and 2 Gy, delivered by tens of minibeams, appeared to be more severe, and they provided more highly damaged cells than in the HRS-negative cells, suggesting that more severe DSB are induced in the "SBRT modes" conditions when HRS occurs in tumor. Each SBRT session can be viewed as hyperfractionated dose delivery by means of hundreds of low dose minibeams. Under current SBRT conditions (i.e., low dose per minibeam and not using ultra-high dose-rate), the response of HRS-positive tumors to SBRT may be enhanced significantly. Interestingly, similar conclusions were reached with HRS-positive and HRS-negative untransformed fibroblast cell lines, suggesting that the HRS phenomenon may also impact the risk of post-RT tissue overreactions.

Five-year survival outcomes in patients with melanoma with complete response to immunotherapy who discontinue therapy.

e21503 Background: Immune checkpoint inhibitor (ICI) therapy for advanced melanoma in the first-line setting often results in durable responses and prolonged overall survival (OS) after achieving a complete response (CR). While generally well-tolerated, there are financial toxicities and treatment related adverse events (TRAEs) associated with ICI use. There are limited data to inform the optimal duration of therapy after CR, and how specific patient factors may lead to variable OS in patients (pts) with CR. Methods: Pts with locally advanced stage III or stage IV melanoma who started first-line ICI therapy with pembrolizumab, nivolumab, or ipilimumab/nivolumab (ipi/nivo) and achieved CR were identified at a single institution under an Institutional Review Board approved protocol. Pts were only included in the sample if they had initiated treatment by 2013 and discontinued therapy by February of 2021 and had documented follow-up at least 1 year after discontinuing ICI therapy. Recurrence rates were determined by the presence of any recurrence after CR. Pts were analyzed by baseline stage (III vs IV), BRAF status, use of steroids for TRAEs, time from treatment start to CR, and total duration of therapy. OS was determined by time from treatment start to death or date of last follow-up. Results: 78 Pts with CRs from ICI therapy who discontinued treatment were identified at the University of Pennsylvania. Median follow-up time was 63 months from ICI treatment start. Median age at treatment start was 65 years (range 33-94). 51 Pts (68%) had an ECOG performance status (PS) of 0 vs 24 (32%) with ECOG PS of 1-2. 21 Pts (27%) had locally advanced stage III and 57 (73%) had stage IV disease. Of stage IV pts, 8 were M1a, 16 M1b, 22 M1c, and 11 M1d. 61 (78%) pts were treated with pembrolizumab, 5 (6%) nivolumab, 12 (15%) ipi/nivo. 34 pts (44%) were treated with steroids for TRAEs. Of the 78 total pts, 13 (16.7%) developed a recurrence after stopping treatment. The median time to recurrence was 57 months (range 9-110). Melanoma specific survival was 96%. Of the pts with recurrence, 3 died of melanoma, 9 are disease free after additional local and/or systemic treatment and one patient is alive with disease. There was no significant difference ( p &lt; 0.05) in OS based on baseline stage, BRAF status, or use of steroids for TRAEs. Pts were treated for a median of 6 months (range 1 day to 24 months). Conclusions: With over 5 years median follow-up time, the majority of pts with advanced melanoma who attain a CR from first-line ICI therapy remain disease free after treatment discontinuation. Patient factors including stage at treatment initiation, BRAF status, and steroid usage during treatment were not associated with significant variation in OS in this cohort. Most pts with recurrences remain disease free after additional local and/or systemic treatment. Few melanoma specific deaths occurred in pts with a CR to ICI who discontinued treatment.

Organisational learning, or organised irresponsibility? Risk, opacity and lesson learning about mental health related deaths

This article examines how deaths related to mental health in England and Wales are investigated and the extent to which lessons are learned in their aftermath. It uses two concepts from academic literature to discuss organisational responses to these deaths: organisational learning, and organised irresponsibility. Organisational learning stresses the importance of learning lessons from data; in contrast, Beck’s concept of organised irresponsibility states that organisational lesson learning is impeded by the fragmented and risk-averse nature of public institutions. The article considers 210 organisational responses to Reports to Prevent Future Deaths (PFDs) issued by Coroners. PFDs are sent to any organisation Coroners believe could act to prevent future deaths. The article identifies three findings: Firstly, organisations tend to produce generic responses rather than addressing specific issues raised by Coroners. Second, organisations tend to cite existing policies as responses to Coroners despite those policies not preventing specific deaths. Third, institutions seek to displace blame onto other organisations in attempting to avoid accepting responsibility for the death. The article adds to the canon of knowledge on deaths in healthcare, and in the care of the state by identifying significant structural weaknesses that impede organisational lesson learning about preventable deaths.

Cuproptosis-related gene PDHX and heat stress-related HSPD1 as potential key drivers associated with cell stemness, aberrant metabolism and immunosuppression in esophageal carcinoma.

Heat stress is fundamental to esophageal carcinoma (ESCA) oncogenesis and progression. Heat stress damages epithelial structure, causing aberrant 'cell death-repair' patterns of esophagus cells and thereby driving tumor occurrence and progression. However, due to the distinctive functions and crosstalk of regulatory cell death (RCD) patterns, the specific cell deaths in ESCA malignancy are still unclear. We analyzed the key regulatory cell death genes involved in heat stress and ESCA progression by using The Cancer Genome Atlas-ESCA database. The least absolute shrinkage and selection operator (LASSO) algorithm was used to filter the key genes. The one-class logistic regression (OCLR) and quanTIseq methods were used to evaluate the cell stemness and immune cell infiltration in ESCA samples. Cell counting kit-8 (CCK8) and wound healing assays were performed to assess the proliferation and migration of cells. We found that cuproptosis may be a potential risk factor of heat stress-related ESCA. Two interrelated genes, HSPD1 and PDHX, were associated with heat stress and cuproptosis and played a role in cell survival, proliferation, migration, metabolism and immunosuppression. We found that cuproptosis promoted ESCA related to heat stress, offering a new therapeutic opportunity to treat this malignant disorder.

Abstract P5-03-06: Effect of Sleep Traits on Subtype Specific Breast Cancer Survival: a Mendelian Randomization Analysis

Abstract Background There is increasing interest in the relationship between sleep traits and both quality of life and survival in breast cancer. Recent work has found that oestrogen receptor positive (ER+) tumour cells are more likely to spread, via the circulation, at night than in the morning, providing support for a potential role of sleep characteristics influencing metastasis and therefore survival from breast cancer. The aim of this study was to investigate causal effects of sleep traits on subtype-specific breast cancer survival. Methods Single-nucleotide polymorphisms (SNPs) identified from GWAS associated with sleep traits with were used as a genetic instruments for Chronotype (N=697,828), Insomnia (N=1,331,010), Sleep Duration (N=446,118), Napping (N=452,633), Daytime sleepiness(N=452,071) and Ease of Getting up (N=461,658). All instruments were identified in data from UK Biobank, except chronotype and insomnia, which were identified in meta-analyses of UK Biobank and 23andme. For all instruments female-specific effect estimates were used. For these SNPs, summary statistics of their association with breast cancer survival were obtained from GWAS meta-analyses of European women from the Breast Cancer Association Consortium (BCAC), (N=91,686, with 7531 breast cancer specific deaths over a median follow-up of 8.1 years). To estimate the causal effect of the sleep traits on breast cancer survival, we applied two-sample MR for both overall and subtype-specific breast cancer (Luminal A-like, Luminal B-like, Human Epidermal Growth Factor 2 (Her2) positive, Her2 negative and triple negative (TNBC)). Further stratification by tumour characteristics at diagnosis and treatment received was also used. Sensitivity analyses were used to assess the robustness of main analyses to MR assumptions. Results For every hour increase in sleep duration, we observed worsening 5-year breast cancer specific survival in patients with ER+ tumours who received endocrine therapy (HR: 2.55, 95% CI: 1.10, 5,82) and for all patients receiving aromatase inhibitors (HR: 9.57, 95% CI: 1.61, 57.10). Conversely, improved 5-year survival was observed in patients with ER- tumours who received chemotherapy (HR: 0.30, 95% CI: 0.10, 0.87) and all patients receiving taxanes (HR: 0.23, 95% CI: 0.05, 0.98). We also observed that an increase in daytime sleepiness improved 15-year survival in patients both overall (HR: 0.34, 95% CI: 0.14, 0.80) and with lymph node negative tumours at diagnosis (HR: 0.12, 95% CI: 0.02, 0.64). Detailed sensitivity analyses are ongoing. Conclusions The current study uses a causal approach to identify potential effects between sleep patterns and breast cancer survival and confirms the previously observed relationships with increased sleep duration and worse survival in ER+ breast cancer. The reasons for opposite effects seen in those with ER- and those receiving taxanes needs further mechanistic work. Although the improved survival in relation to increased daytime sleepiness appears to be in-keeping with previous findings, this may largely reflect shorter sleep duration. Further work accurately characterising sleep quality, rather than duration in those with breast cancer, examining the effects on quality of life and survival and establishing mechanisms are needed. Citation Format: Bryony Hayes, Richard Martin, Deborah Lawlor, Rebecca Richmond, Tim Robinson. Effect of Sleep Traits on Subtype Specific Breast Cancer Survival: a Mendelian Randomization Analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-06.

Abstract P115: Ethnic Differences in Cardiovascular Disease Deaths Among African American, African Immigrant and Afro-Caribbean Adults in the 1999-2018 National Health Interview Surveys

Background: Black persons are an heterogenous group in the US and bear a disparate higher burden of worse cardiovascular disease (CVD) outcomes. Our objective was to examine ethnic differences in CVD mortality among Black subgroups; African Americans(AAs); African Immigrants(AIs); and Afro Caribbeans(ACs). Methods: We analyzed the 1999-2018 National Health Interview Survey data, prospectively linked to mortality records in the National Death Index on 23,169,679 Black adults. The outcomes was CVD mortality, defined as CVD and cerebrovascular deaths, which was modelled as time till death (in years). This was calculated from each survey year till time of death or December 31, 2019 (administrative censoring) for those who survived. Using multivariable Cox proportional hazards regression analyses to model the survival function, we evaluated differences in CVD-and cerebrovascular-cause specific deaths among the three groups with progressive adjustment for age, sex, socioeconomic status and CVD risk factors. Results: With median of 10 years of mortality follow-up, there were 2.44, and 1.86 CVD deaths per 1,000 person-years among AA, and foreign born black adults (AIs and ACs combined), respectively. CVD mortality hazard was 81% lower in AIs [hazard ratio [HR], 0.19 (95% CI, 0.13–0.29], Table ) and 54% lower in ACs [HR, 0.46 (95% CI, 0.40–0.53], than among AAs. Compared to AAs, age-and sex-adjusted CVD mortality hazard was lower among AIs by 66% [HR, 0.34 (95% CI, 0.23–0.51], Table ) and ACs (HR, 0.46 [95% CI, 0.40–0.53]) by 54% (unchanged from unadjusted). In the fully adjusted model with SES and CVD risk factors adjustment, ACs had 41% lower adjusted CVD mortality hazard than AA adults (HR, 0.59 [95% CI, 0.45–0.77]). Conclusions: Cardiovascular deaths were higher among US-born AAs than foreign-born ACs. Nativity status is an important determinant of CVD mortality, and the heterogeneity of this population should be considered in health disparities research and interventions.

Early detection of gastric cancer in China: progress and opportunities.

In the past decade, the Chinese government has committed to promoting gastric cancer (GC) prevention and control[1][1],[2][2]. GC is a major malignancy globally, and nearly half of GC cases and specific deaths worldwide occur in China; moreover, GC is frequently diagnosed in local advanced or

Examining COVID-19 mortality rates by race and ethnicity among incarcerated people in 11 U.S. state prisons (March–October 2021)

BackgroundPopulations who are incarcerated have experienced disproportionately high coronavirus disease 2019 (COVID-2019) mortality rates compared to the general population. However, mortality rates by race/ethnicity from federal, state, and local carceral settings are largely unavailable due to unregulated reporting; therefore, racial/ethnic inequities have yet to be examined. We aimed to estimate coronavirus disease 2019 (COVID-19) mortality rates among individuals incarcerated in U.S. state prisons by race and ethnicity (RE). MethodsPublic records requests to state Departments of Corrections were used to identify deaths from COVID-19 among incarcerated adults occurring from March 1-October 1, 2020. We requested race, ethnicity, and age specific data on deaths and custody populations; sufficient data to calculate age-adjusted rates were obtained for 11 state systems. Race and ethnic specific unadjusted deaths rates per 100,000 persons were calculated overall and by state, based on March 1, 2020 custody populations. Rate ratios (RR) and 95% confidence intervals (95%CI) compared aggregated age-adjusted death rates by race and ethnicity, with White individuals as the reference group. ResultsOf all COVID-related deaths in U.S. prisons through October 2020, 23.35% (272 of 1165) were captured in our analyses. The average age at COVID-19 death was 63 years (SD = 10 years) and was significantly lower among Black (60 years, SD = 11 years) compared to White adults (66 years, SD = 10 years; p < 0.001). In age-standardized analysis, COVID-19 death rates were significantly higher among Black (RR = 1.93, 95% CI: 1.25–2.99), Hispanic (RR = 1.81, 95% CI: 1.10–2.96) and those of Other racial and ethnic groups (RR = 2.60, 95% CI: 1.01–6.67) when compared to White individuals. ConclusionsAge-standardized death rates were higher among incarcerated Black, Hispanic and those of Other racial and ethnic groups compared to their White counterparts. Greater data transparency from all carceral systems is needed to better understand populations at disproportionate risk of COVID-19 morbidity and mortality.

Respiratory symptoms and cardiovascular causes of deaths: A population-based study with 45 years of follow-up.

This study determined the association between respiratory symptoms and death from cardiovascular (CV) diseases during 45 years in a pooled sample of four cohorts of random samples of the Norwegian population with 95,704 participants. Respiratory symptoms were assessed using a modification of the MRC questionnaire on chronic bronchitis. We analyzed the association between respiratory symptoms and specific cardiovascular deaths by using Cox regression analysis with age as the time variable, accounting for cluster-specific random effects using shared frailty for study cohort. Hazard ratios (HR) for death were adjusted for sex, highest attained education, smoking habits, occupational air pollution, and birth cohort. Overall, 12,491 (13%) of participants died from CV diseases: 4,123 (33%) acute myocardial infarction, 2,326 (18%) other ischemic heart disease, 2,246 (18%) other heart diseases, 2,553 (20%) cerebrovascular diseases, and 1,120 (9%) other vascular diseases. The adjusted HR (95% confidence interval) for CV deaths was 1.9 (1.7-2.1) in men and 1.5 (1.2-1.9) in women for "yes" to the question "Are you breathless when you walk on level ground at an ordinary pace?". The same item response showed an adjusted HR for death from acute myocardial infarction of 1.8 (1.5-2.1), other ischemic heart disease 2.2 (1.8-2.7), other heart diseases 1.5 (1.1-1.9), cerebrovascular disease 1.8 (1.5-2.3), and other circulatory diseases 1.7 (1.2-2.4). The adjusted HR for CV death was 1.3 (1.2-1.4) when answering positive to the question" Are you more breathless than people of your own age when walking uphill?". However, positive answers to questions on cough, phlegm, wheezing and attacks of breathlessness were after adjustments not associated with early CV deaths. The associations between CV deaths and breathlessness were also present in never smokers. Self-reported breathlessness was associated with CV deaths and could be an early marker of CV deaths.