Mechanism of Ventricular Tachycardia Occurring in Chronic Myocardial Infarction Scar.

Cardiac arrest is the leading cause of death in the more economically developed countries. Ventricular tachycardia associated with myocardial infarct is a prominent cause of cardiac arrest. Ventricular arrhythmias occur in 3 phases of infarction: during the ischemic event, during the healing phase, and after the scar matures. Mechanisms of arrhythmias in these phases are distinct. This review focuses on arrhythmia mechanisms for ventricular tachycardia in mature myocardial scar. Available data have shown that postinfarct ventricular tachycardia is a reentrant arrhythmia occurring in circuits found in the surviving myocardial strands that traverse the scar. Electrical conduction follows a zigzag course through that area. Conduction velocity is impaired by decreased gap junction density and impaired myocyte excitability. Enhanced sympathetic tone decreases action potential duration and increases sarcoplasmic reticular calcium leak and triggered activity. These elements of the ventricular tachycardia mechanism are found diffusely throughout scar. A distinct myocyte repolarization pattern is unique to the ventricular tachycardia circuit, setting up conditions for classical reentry. Our understanding of ventricular tachycardia mechanisms continues to evolve as new data become available. The ultimate use of this information would be the development of novel diagnostics and therapeutics to reliably identify at-risk patients and prevent their ventricular arrhythmias.

Time-Restricted Feeding Reduces Atherosclerosis in LDLR KO Mice but Not in ApoE Knockout Mice.

BACKGROUND: Dyslipidemia increases cardiovascular disease risk, the leading cause of death worldwide. Under time-restricted feeding (TRF), wherein food intake is restricted to a consistent window of <12 hours, weight gain, glucose intolerance, inflammation, dyslipidemia, and hypercholesterolemia are all reduced in mice fed an obesogenic diet. LDLR (low-density lipoprotein receptor) mutations are a major cause of familial hypercholesterolemia and early-onset cardiovascular disease. METHODS: We subjected benchmark preclinical models, mice lacking LDLR-knockout or ApoE knockout to ad libitum feeding of an isocaloric atherogenic diet either ad libitum or 9 hours TRF for up to 13 weeks and assessed disease development, mechanism, and global changes in hepatic gene expression and plasma lipids. In a regression model, a subset of LDLR-knockout mice were ad libitum fed and then subject to TRF. RESULTS: TRF could significantly attenuate weight gain, hypercholesterolemia, and atherosclerosis in mice lacking the LDLR-knockout mice under experimental conditions of both prevention and regression. In LDLR-knockout mice, increased hepatic expression of genes mediating ß-oxidation during fasting is associated with reduced VLDL (very-low-density lipoprotein) secretion and lipid accumulation. Additionally, increased sterol catabolism coupled with fecal loss of cholesterol and bile acids contributes to the atheroprotective effect of TRF. Finally, TRF alone or combined with a cholesterol-free diet can reduce atherosclerosis in LDLR-knockout mice. However, mice lacking ApoE, which is an important protein for hepatic lipoprotein reuptake do not respond to TRF. CONCLUSIONS: In a preclinical animal model, TRF is effective in both the prevention and regression of atherosclerosis in LDLR knockout mice. The results suggest TRF alone or in combination with a low-cholesterol diet can be a lifestyle intervention for reducing cardiovascular disease risk in humans.

Polygenic Risk Score Associates With Atherosclerotic Plaque Characteristics at Autopsy.

BACKGROUND: Polygenic risk scores (PRSs) for coronary artery disease (CAD) potentially improve cardiovascular risk prediction. However, their relationship with histopathologic features of CAD has never been examined systematically. METHODS: From 4327 subjects referred to CVPath by the State of Maryland Office Chief Medical Examiner for sudden death between 1994 and 2015, 2455 cases were randomly selected for genotyping. We generated PRS from 291 known CAD risk loci. Detailed histopathologic examination of the coronary arteries was performed in all subjects. The primary study outcome measurements were histopathologic plaque features determining severity of atherosclerosis, including %stenosis, calcification, thin-cap fibroatheromas, and thrombotic CAD. RESULTS: After exclusion of cases with insufficient DNA sample quality or with missing data, 954 cases (mean age, 48.8±14.7 years; 75.7% men) remained in the final study cohort. Subjects in the highest PRS quintile exhibited more severe atherosclerosis compared with subjects in the lowest quintile, with greater %stenosis (80.3%±27.0% versus 50.4%±38.7%; adjusted P<0.001) and a higher frequency of calcification (69.6% versus 35.8%; adjusted P=0.004) and thin-cap fibroatheroma (26.7% versus 9.5%; adjusted P=0.007). Even after adjustment for traditional CAD risk factors, subjects within the highest PRS quintile had higher odds of severe atherosclerosis (ie, ≥75% stenosis; adjusted odds ratio, 3.77 [95% CI, 2.10-6.78]; P<0.001) and plaque rupture (adjusted odds ratio, 4.05 [95% CI, 2.26-7.24]; P<0.001). Moreover, subjects within the highest quintile had higher odds of CAD-associated cause of death, especially among those aged ≤50 years (adjusted odds ratio, 4.08 [95% CI, 2.01-8.30]; P<0.001). No statistically significant associations were observed with plaque erosion after adjusting for covariates. CONCLUSIONS: This is the first autopsy study investigating associations between PRS and atherosclerosis severity at the histopathologic level in subjects with sudden death. Our pathological analysis suggests PRS correlates with plaque burden and features of advanced atherosclerosis and may be useful as a method for CAD risk stratification, especially in younger subjects.

Mortality Rates of the Spanish Flu and Coronavirus Disease 2019 in the Netherlands: A Historical Comparison.

The coronavirus disease 2019 (COVID-19) pandemic has been called the deadliest disease event in history. In this study, we compared the cause-specific mortality rate of the Spanish flu (1918-1920) with that of COVID-19 (2020-2022) in the Netherlands. During the periods of exposure, about 50 000 people died of COVID-19 and 32 000 people of the Spanish flu. In absolute numbers, COVID-19 seems to be deadlier than Spanish flu. However, the crude mortality rates for COVID-19 and Spanish flu were 287 and 486 per 100 000 inhabitants, respectively. Comparing age-standardized mortality rates, there would have been 28 COVID-19- and 194 Spanish flu-related deaths in 1918-1920, or 214 Spanish flu- and 98 COVID-19-related deaths in 2020-2022 per 100 000 inhabitants per year. Thus, taking the population differences into account, the Spanish flu would have been deadlier than COVID-19.

From flesh to bones: Multi-omics approaches in forensic science.

Recent advancements in omics techniques have revolutionised the study of biological systems, enabling the generation of high-throughput biomolecular data. These innovations have found diverse applications, ranging from personalised medicine to forensic sciences. While the investigation of multiple aspects of cells, tissues or entire organisms through the integration of various omics approaches (such as genomics, epigenomics, metagenomics, transcriptomics, proteomics and metabolomics) has already been established in fields like biomedicine and cancer biology, its full potential in forensic sciences remains only partially explored. In this review, we have presented a comprehensive overview of state-of-the-art analytical platforms employed in omics research, with specific emphasis on their application in the forensic field for the identification of the cadaver and the cause of death. Moreover, we have conducted a critical analysis of the computational integration of omics approaches, and highlighted the latest advancements in employing multi-omics techniques for forensic investigations.

Time Trends in Causes of Death in People With HIV: Insights From the Swiss HIV Cohort Study.

BACKGROUND: Advancements in access to antiretroviral therapy (ART) and human immunodeficiency virus (HIV) care have led to a decline in AIDS-related deaths among people with HIV (PWH) in Switzerland. However, data on the ongoing changes in causes of death among PWH over the past 15 years are scarce. METHODS: We investigated all reported deaths in the Swiss HIV Cohort Study between 2005 and 2022. Causes of death were categorized using the Coding Causes of Death in HIV protocol. The statistical analysis included demographic stratification to identify time trends and logistic regression models to determine associated factors for the underlying cause of death. RESULTS: In total, 1630 deaths were reported, with 23.7% of individuals assigned female sex at birth. These deaths included 147 (9.0%) HIV/AIDS-related deaths, 373 (22.9%) due to non-AIDS, non-hepatic cancers, 166 (10.2%) liver-related deaths, and 158 (9.7%) cardiovascular-related deaths. The median age at death (interquartile range) increased from 45.0 (40.0-53.0) years in 2005-2007 to 61.0 (56.0-69.5) years in 2020-2022. HIV/AIDS- and liver-related deaths decreased, whereas deaths from non-AIDS, non-hepatic cancers increased and cardiovascular-related deaths remained relatively stable. CONCLUSIONS: The proportionally decreasing HIV/AIDS and liver-related deaths showcase the effectiveness of ART, comprehensive HIV patient care, and interventions targeting hepatitis C virus coinfection. Future research should focus on managing cancer and cardiovascular-related conditions as the new leading causes of death among PWH. Comprehensive healthcare strategies focusing on non-AIDS-related comorbid conditions, cancer management, and sustaining liver and cardiovascular health are needed to bridge the ongoing health disparities between PWH and the general population.

ATF2/BAP1 Axis Mediates Neuronal Apoptosis After Subarachnoid Hemorrhage via P53 Pathway.

BACKGROUND: Neuronal apoptosis plays an essential role in the pathogenesis of brain injury after subarachnoid hemorrhage (SAH). BAP1 (BRCA1-associated protein 1) is considered to exert pro-apoptotic effects in multiple diseases. However, evidence supporting the effect of BAP1 on the apoptotic response to SAH is lacking. Therefore, we aimed to confirm the role of BAP1 in SAH-induced apoptosis. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to detect BAP1 expression in the cerebrospinal fluid. Endovascular perforation was performed in mice to induce SAH. Lentiviral short hairpin RNA targeting BAP1 mRNA was transduced into the ipsilateral cortex of mice with SAH to investigate the role of BAP1 in neuronal damage. Luciferase and coimmunoprecipitation assays were performed to investigate the mechanism through which BAP1 participates in hemin-induced SAH. RESULTS: First, BAP1 expression was upregulated in the cerebrospinal fluid of patients with SAH and positively associated with unfavorable outcomes. ATF2 (activating transcription factor-2) then regulated BAP1 expression by binding to the BAP1 promoter. In addition, BAP1 overexpression enhanced P53 activity and stability by reducing P53 proteasome-mediated degradation. Subsequently, elevated P53 promoted neuronal apoptosis via the P53 pathway. Inhibition of the neuronal BAP1/P53 axis significantly reduced neurological deficits and neuronal apoptosis and improved neurological dysfunction in mice after SAH. CONCLUSIONS: Our results suggest that the neuronal ATF2/BAP1 axis exerts a brain-damaging effect by modulating P53 activity and stability and may be a novel therapeutic target for SAH.

Assessing the Quality of Cause-of-Death Reporting Before and During the COVID-19 Pandemic.

This study assessed the quality of cause-of-death reporting in the US before and during the COVID-19 pandemic. We used the selection rate and the adjusted odds ratio (aOR) to analyze each cause identified by the National Center for Health Statistics as unsuitable for the underlying cause of death (UCOD). The selection rate was defined as the proportion of deaths with mention of a particular unsuitable UCOD on the death certificate where that cause was ultimately selected as the UCOD. Out of 36 unsuitable UCODs, 33 exhibited a significant decline in selection rates from 2019 to 2021. However, when deaths with mention of COVID-19 on the death certificate were excluded, only 19 causes revealed a significant decline. In analyses that controlled for the age of decedents, aORs in 2021 were significantly lower compared with 2019 for 26 causes, and this number decreased to 17 causes in analyses that excluded COVID-19-related deaths. In conclusion, the overall quality of COD reporting improved during the COVID-19 pandemic, attributable mainly to the fact that over one-tenth of the deaths were related to COVID-19. Yet, for deaths that did not involve COVID-19, improvements in the quality of COD reporting were less prominent for certain causes.

Late mortality among 5-year survivors of childhood cancer: A systematic review and meta-analysis.

BACKGROUND: Childhood cancer survivors are at increased risk of late mortality (death ≥5 years after diagnosis) from cancer recurrence and treatment-related late effects. The authors conducted a systematic review and meta-analysis to provide comprehensive estimates of late mortality risk among survivors internationally and to investigate differences in risk across world regions. METHODS: Health sciences databases were searched for cohort studies comprised of 5-year childhood cancer survivors in which the risk of mortality was evaluated across multiple cancer types. Eligible studies assessed all-cause mortality risk in survivors relative to the general population using the standardized mortality ratio (SMR). The absolute excess risk (AER) was assessed as a secondary measure to examine excess deaths. Cause-specific mortality risk was also assessed, if reported. SMRs from nonoverlapping cohorts were combined in subgroup meta-analysis, and the effect of world region was tested in univariate meta-regression. RESULTS: Nineteen studies were included, and cohort sizes ranged from 314 to 77,423 survivors. Throughout survivorship, SMRs for all-cause mortality generally declined, whereas AERs increased after 15-20 years from diagnosis in several cohorts. All-cause SMRs were significantly lower overall in North American studies than in European studies (relative SMR, 0.63; 95% confidence interval, 0.49-0.80). SMRs for subsequent malignant neoplasms and for cardiovascular, respiratory, and external causes did not vary significantly between world regions. CONCLUSIONS: The current findings suggest that late mortality risk may differ significantly between world regions, but these conclusions are based on a limited number of studies with considerable heterogeneity. Reasons for regional differences remain unclear but may be better elucidated through future analyses of individual-level data.

Avoiding lead-time bias by estimating stage-specific proportions of cancer and non-cancer deaths.

PURPOSE: Understanding how stage at cancer diagnosis influences cause of death, an endpoint that is not susceptible to lead-time bias, can inform population-level outcomes of cancer screening. METHODS: Using data from 17 US Surveillance, Epidemiology, and End Results registries for 1,154,515 persons aged 50-84 years at cancer diagnosis in 2006-2010, we evaluated proportional causes of death by cancer type and uniformly classified stage, following or extrapolating all patients until death through 2020. RESULTS: Most cancer patients diagnosed at stages I-II did not go on to die from their index cancer, whereas most patients diagnosed at stage IV did. For patients diagnosed with any cancer at stages I-II, an estimated 26% of deaths were due to the index cancer, 63% due to non-cancer causes, and 12% due to a subsequent primary (non-index) cancer. In contrast, for patients diagnosed with any stage IV cancer, 85% of deaths were attributed to the index cancer, with 13% non-cancer and 2% non-index-cancer deaths. Index cancer mortality from stages I-II cancer was proportionally lowest for thyroid, melanoma, uterus, prostate, and breast, and highest for pancreas, liver, esophagus, lung, and stomach. CONCLUSION: Across all cancer types, the percentage of patients who went on to die from their cancer was over three times greater when the cancer was diagnosed at stage IV than stages I-II. As mortality patterns are not influenced by lead-time bias, these data suggest that earlier detection is likely to improve outcomes across cancer types, including those currently unscreened.

Mortality in patients with psoriatic arthritis in Sweden: a nationwide, population-based cohort study.

OBJECTIVES: To compare all-cause mortality and causes of death between patients with psoriatic arthritis (PsA) and the general population in Sweden. METHODS: Adults with at least one main PsA diagnosis (International Classification of Diseases-10: L40.5/M07.0-M07.3) from outpatient rheumatology/internal medicine departments 2001-2017 were identified from the National Patient Register. Each case was matched to five population comparator-subjects on sex/county/age at the case's first arthritis diagnosis. Follow-up ran from 1 January 2007, or from first PsA diagnosis thereafter, until death, emigration or 31 December 2018. Mortality was assessed overall, and stratified by sex and duration since diagnosis (diagnosis before/after 1 January 2007), using matched Cox proportional hazard regression (excluding/including adjustments for comorbidity) or Breslow test, as appropriate. Incidence rate ratios (IRR) of death, overall and stratified by sex/duration since diagnosis/age, as well as causes of death in PsA cases and comparator-subjects were also described. RESULTS: All-cause mortality was elevated in PsA (HR: 1.11 (95% CI: 1.07 to 1.16); IRR: 1.18 (95% CI: 1.13 to 1.22)), mainly driven by increased risks in women (HR: 1.23 (95% CI: 1.16 to 1.30)) and cases with longer time since diagnosis (HR: 1.18 (95% CI: 1.12 to 1.25)). IRR of death were significantly increased for all ages except below 40 years, with the numerically highest point-estimates for ages 40-59 years. When adjusted for comorbidity, however, the elevated mortality risk in PsA disappeared. Causes of death were similar among PsA cases/comparator-subjects, with cardiovascular disease and malignancy as the leading causes. CONCLUSIONS: Mortality risk in PsA in Sweden was about 10% higher than in the general population, driven by excess comorbidity and with increased risks mainly in women and patients with longer disease duration.

The changing landscape of both causes and locations of death in a regional HIV population 2010-2021.

BACKGROUND: Although HIV-related deaths among people with HIV have dramatically decreased, deaths from other medical conditions and non-medical events have increased. The location of death among people with HIV remains underreported. OBJECTIVES: We reviewed the deaths, causes of death, and reported location of death (i.e. within or outside of medical settings) of all people with HIV with the Southern Alberta Cohort, Calgary, Canada, between 1 January 2010 and 1 January 2022. METHODS: This was a retrospective longitudinal cohort study reviewing all deaths within a comprehensive geographically defined HIV cohort over 11 years. RESULTS: Deaths from HIV-related causes decreased from 52% of all deaths in 2010 to 14% in 2021. In 2021, non-HIV medical deaths increased from 38% to 44%, and non-medical deaths (e.g. violence, suicide, drug overdose) increased from 0.5% to 39%. Of non-medical deaths, 67% resulted from substance use/overdose. Overall, deaths in any medical setting decreased from 91% in 2010 to 39% in 2021; 61% of all deaths occurred in a medical setting (e.g. hospital/emergency department or supported/long-term/hospice care), 27% in a residence, and 9% in the community. CONCLUSION: The shifting causes of death (i.e. fewer HIV-related deaths, more overdose deaths) and location of death (i.e. fewer in medical settings, more at home/in the community) requires close monitoring so future resources can be matched to predicted patient needs.

Causes of death among Australians with type 1 or type 2 diabetes, 2002-2019.

AIMS: This population-based study sought to explore in detail the conditions driving the diversification in causes of death among people with diabetes. METHODS: We linked Australians with type 1 or type 2 diabetes of all ages on the National Diabetes Services Scheme to the National Death Index for 2002-2019. We investigated the proportional contributions of different causes of death to total deaths over time across eight categories of causes of death, stratified by sex and diabetes type. The underlying causes of death were classified according to the International Classification of Diseases, Tenth Revision codes. RESULTS: Between 2002 and 2019, there was a shift in the causes of death among Australians with diabetes away from cardiovascular disease. The proportion of deaths attributed to cardiovascular disease declined in both sexes (ptrend <0.001), most substantially among women with type 2 diabetes from 48.2% in 2002 to 30.7% in 2019. Among men with type 2 diabetes, cancer replaced cardiovascular disease as the leading cause of death. The proportion of deaths due to dementia increased overall, from 2% in 2002 to over 7% in 2019, and across all age groups, notably from 1% to 4% in those aged 70-79. The proportion of deaths due to falls and Parkinson's disease also increased. CONCLUSIONS: There has been a shift of causes of death among those with diabetes away from cardiovascular disease. The proportion of deaths due to conditions such as dementia and falls is increasing among those with diabetes, which will require consideration when planning future resource allocation.

Cause-specific mortality in a population-level cohort of diffuse large B-cell lymphoma following chemotherapy in the early 21st century.

Diffuse large B-cell lymphoma (DLBCL) is a severe non-Hodgkin's lymphoma. Life expectancy has improved with rituximab, but cause-specific mortality data is lacking. Using the Surveillance, Epidemiology, and End Results (SEER) database to study 27,449 individuals aged 20-74 years diagnosed with primary DLBCL who received chemotherapy between 2000 and 2019, we calculated standardized mortality rate (SMR) and excess absolute risk (EAR) and examined the connection between age, sex, time after diagnosis, and cause of death. Based on 12,205 deaths, 68.7% were due to lymphoma, 20.1% non-cancer causes, and 11.2% other cancers. Non-cancer mortality rates (SMR 1.2; EAR, 21.5) increased with DLBCL compared to the general population. The leading non-cancer death causes were cardiovascular (EAR, 22.6; SMR, 1.6) and infectious (EAR, 9.0; SMR, 2.9) diseases with DLBCL. Risks for non-cancer death and solid neoplasms are highest within the first diagnosis year, then decrease. Among socioeconomic factors, being white, being married, and having a higher income were favorable factors for reducing non-cancer mortality. To improve survival, close surveillance, assessment of risk factors, and early intervention are needed.

Maternal mortality in the United States: are the high and rising rates due to changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance?

BACKGROUND: National Vital Statistics System reports show that maternal mortality rates in the United States have nearly doubled, from 17.4 in 2018 to 32.9 per 100,000 live births in 2021. However, these high and rising rates could reflect issues unrelated to obstetrical factors, such as changes in maternal medical conditions or maternal mortality surveillance (eg, due to introduction of the pregnancy checkbox). OBJECTIVE: This study aimed to assess if the high and rising rates of maternal mortality in the United States reflect changes in obstetrical factors, maternal medical conditions, or maternal mortality surveillance. STUDY DESIGN: The study was based on all deaths in the United States from 1999 to 2021. Maternal deaths were identified using the following 2 approaches: (1) per National Vital Statistics System methodology, as deaths in pregnancy or in the postpartum period, including deaths identified solely because of a positive pregnancy checkbox, and (2) under an alternative formulation, as deaths in pregnancy or in the postpartum period, with at least 1 mention of pregnancy among the multiple causes of death on the death certificate. The frequencies of major cause-of-death categories among deaths of female patients aged 15 to 44 years, maternal deaths, deaths due to obstetrical causes (ie, direct obstetrical deaths), and deaths due to maternal medical conditions aggravated by pregnancy or its management (ie, indirect obstetrical deaths) were quantified. RESULTS: Maternal deaths, per National Vital Statistics System methodology, increased by 144% (95% confidence interval, 130-159) from 9.65 in 1999-2002 (n=1550) to 23.6 per 100,000 live births in 2018-2021 (n=3489), with increases occurring among all race and ethnicity groups. Direct obstetrical deaths increased from 8.41 in 1999-2002 to 14.1 per 100,000 live births in 2018-2021, whereas indirect obstetrical deaths increased from 1.24 to 9.41 per 100,000 live births: 38% of direct obstetrical deaths and 87% of indirect obstetrical deaths in 2018-2021 were identified because of a positive pregnancy checkbox. The pregnancy checkbox was associated with increases in less specific and incidental causes of death. For example, maternal deaths with malignant neoplasms listed as a multiple cause of death increased 46-fold from 0.03 in 1999-2002 to 1.42 per 100,000 live births in 2018-2021. Under the alternative formulation, the maternal mortality rate was 10.2 in 1999-2002 and 10.4 per 100,000 live births in 2018-2021; deaths from direct obstetrical causes decreased from 7.05 to 5.82 per 100,000 live births. Deaths due to preeclampsia, eclampsia, postpartum hemorrhage, puerperal sepsis, venous complications, and embolism decreased, whereas deaths due to adherent placenta, renal and unspecified causes, cardiomyopathy, and preexisting hypertension increased. Maternal mortality increased among non-Hispanic White women and decreased among non-Hispanic Black and Hispanic women. However, rates were disproportionately higher among non-Hispanic Black women, with large disparities evident in several causes of death (eg, cardiomyopathy). CONCLUSION: The high and rising rates of maternal mortality in the United States are a consequence of changes in maternal mortality surveillance, with reliance on the pregnancy checkbox leading to an increase in misclassified maternal deaths. Identifying maternal deaths by requiring mention of pregnancy among the multiple causes of death shows lower, stable maternal mortality rates and declines in maternal deaths from direct obstetrical causes.

Stroke Genetics: Discovery, Insight Into Mechanisms, and Clinical Perspectives.

Stroke is the second leading cause of death worldwide and a complex, heterogeneous condition. In this review, we provide an overview of the current knowledge on monogenic and multifactorial forms of stroke, highlighting recent insight into the continuum between these. We describe how, in recent years, large-scale genome-wide association studies have enabled major progress in deciphering the genetic basis for stroke and its subtypes, although more research is needed to interpret these findings. We cover the potential of stroke genetics to reveal novel pathophysiological processes underlying stroke, to accelerate the discovery of new therapeutic approaches, and to identify individuals in the population who are at high risk of stroke and could be targeted for tailored preventative interventions.

Treatment patterns in patients with systemic lupus erythematosus in New Zealand.

OBJECTIVES: This study aims to explore the treatment pattern of systemic lupus erythematosus (SLE) in Aotearoa/New Zealand. METHODS: SLE patients were linked to the pharmaceutical dispensing data. The use of publicly funded anti-malarials, immunomodulators, biologics, glucocorticoids and bisphosphonates were compared by gender, ethnicity, age group, socioeconomic status and year of SLE identification. Adherence to hydroxychloroquine was examined using the medication possession ratio (MPR), with a MPR of ≥0.8 considered as high adherence. RESULTS: Of the 2631 SLE patients, 73.8% used hydroxychloroquine, 64.1% used immunomodulators/biologics and 68.0% used 5 mg or more prednisone daily for at least 90 days. Women were more likely to use hydroxychloroquine than men. Asian patients had a different treatment pattern than other ethnic groups, and Maori were less likely to use hydroxychloroquine. The proportions of patients using different treatments decreased with age. Of the patients using hydroxychloroquine, 54.5% had high adherence. For patients over 40 years old and on long term prednisone, 47.3% had bisphosphonates and this figure was 17.8% for patients under the age of 40 years old. Patients with better socioeconomic status had a higher probability of using bisphosphonates than patients with lower socioeconomic status. CONCLUSIONS: Adherence to hydroxychloroquine in these patients varied and was lower in men and in Maori. Prednisone is commonly prescribed and used long term. Half of those over the age of 40 years old co-administered bisphosphonate. Further research is needed to identify the reasons for these discrepancies on SLE treatments by gender, ethnicity, age and socioeconomic status.

Trends in underlying causes of death in allogeneic hematopoietic cell transplant recipients over the last decade.

OBJECTIVES: Improved survival after hematopoietic cell transplantation (HCT) and an increasingly comorbid transplant population may give rise to new trends in the causes of death. METHODS: This study includes all adult allogeneic HCT recipients transplanted at Rigshospitalet between January 1, 2010 and December 31, 2019. Underlying causes of death were determined using the Classification of Death Causes after Transplantation (CLASS) method. RESULTS: Among 802 HCT recipients, 289 died during the study period. The main causes of death were relapse (N = 133, 46.0%), graft-versus-host disease (GvHD) (N = 64, 22.1%) and infections (N = 35, 12.1%). Multivariable analyses showed that with increasing transplant calendar year, a decreased risk of all-cause mortality (HR 0.92, 95% CI 0.87-0.97) and death from GvHD (HR 0.87, 95% CI 0.78-0.97) was identified, but not for other specific causes. Standardized mortality ratios (SMRs) for all-cause mortality decreased from 23.8 (95% CI 19.1-28.5) to 18.4 (95% CI 15.0-21.9) for patients transplanted in 2010-2014 versus 2015-2019, while SMR for patients who died from GvHD decreased from 8.19 (95% CI 5.43-10.94) to 3.65 (95% CI 2.13-5.18). CONCLUSIONS: As risk of all-cause mortality and death from GvHD decreases, death from relapse remains the greatest obstacle in further improvement of survival after HCT.

Validation of malaria-attributed deaths using verbal autopsy studies: a systematic review.

BACKGROUND: Malaria contributes substantially to the persistent burden of child deaths in sub-Saharan Africa. Accurate and comprehensive malaria mortality data are crucial to monitor the progress in reducing malaria incidence and mortality. Verbal Autopsy (VA) ascertains the cause of death despite its limitations leading to misclassification errors. Minimally Invasive Tissue Sampling (MITS) is being conducted in some settings as an alternative to Complete Diagnostic Autopsy (CDA). The present study examines the validity of malaria-related deaths comparing VA diagnoses with those obtained through MITS and/or CDA. METHODS: A comprehensive literature search for original studies in English language using Ovid MEDLINE, Ovid Embase, CINAHL via EBSCO, Scopus, The Cochrane Library via Wiley, Google Scholar and searching the MITS Surveillance Alliance papers was carried out. The reference period was January 1, 1990-March 31, 2024. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. RESULTS: Among 71 articles identified in the databases, 21 matched the eligibility criteria. Qualitative syntheses showed that malaria Cause Specific Mortality Fractions (CSMFs) across various studies ranged from 2 to 31%. Plasmodium falciparum was mostly responsible for these deaths and the most common complications were anaemia and cerebral malaria. The sensitivity and specificity of the VA validation studies ranged from 18.4% to 33% and from 86.6% to 97%, respectively, and there was a high level of misclassification for both InSilico and Expert Algorithm VA for malaria compared to MITS. The overall concordance rates between MITS and CDA diagnoses ranged from 68 to 90%, with the highest concordance seen in deaths due to infectious diseases and malignant tumours. Clinical data increased diagnostic coincidence between MITS blind to clinical data and the gold standard CDA by 11%. CONCLUSIONS: The comprehensive review finds that MITS demonstrated better accuracy compared to VA in diagnosing malaria-attributed deaths, particularly in hospital settings. The high specificity of malaria in VA diagnosis suggests population-based estimates of the proportion of deaths due to malaria are broadly plausible.

Automated detection of fatal cerebral haemorrhage in postmortem CT data.

During the last years, the detection of different causes of death based on postmortem imaging findings became more and more relevant. Especially postmortem computed tomography (PMCT) as a non-invasive, relatively cheap, and fast technique is progressively used as an important imaging tool for supporting autopsies. Additionally, previous works showed that deep learning applications yielded robust results for in vivo medical imaging interpretation. In this work, we propose a pipeline to identify fatal cerebral haemorrhage on three-dimensional PMCT data. We retrospectively selected 81 PMCT cases from the database of our institute, whereby 36 cases suffered from a fatal cerebral haemorrhage as confirmed by autopsy. The remaining 45 cases were considered as neurologically healthy. Based on these datasets, six machine learning classifiers (k-nearest neighbour, Gaussian naive Bayes, logistic regression, decision tree, linear discriminant analysis, and support vector machine) were executed and two deep learning models, namely a convolutional neural network (CNN) and a densely connected convolutional network (DenseNet), were trained. For all algorithms, 80% of the data was randomly selected for training and 20% for validation purposes and a five-fold cross-validation was executed. The best-performing classification algorithm for fatal cerebral haemorrhage was the artificial neural network CNN, which resulted in an accuracy of 0.94 for all folds. In the future, artificial neural network algorithms may be applied by forensic pathologists as a helpful computer-assisted diagnostics tool supporting PMCT-based evaluation of cause of death.