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This study investigates acute myeloid leukemia/lymphoblastic leukemia (AML/ALL) through a 14-year analysis (2009–2022) of 46 autopsied cases (age >12 years). B-ALL was the dominant subtype (34.8%). Liver and spleen were the common sites of active leukemia (63% cases). Symptoms like dyspnea and altered sensorium associated significantly with heart (p =.031) and brain leukostasis (p =.006). Measurable residual disease (MRD) negativity correlated with disease-free status outside the bone marrow, while MRD-positive cases displayed leukemic infiltrates. Infections were identified in 23 autopsied cases, notably linked to post-induction and post-transplant fatalities. Surprisingly, 18 of these 23 cases had unexpected infections mainly fungal (13 cases) with Aspergillus species as the most common. Diagnostic discrepancies were identified in 48% of cases. Malignant infiltration (46%) and infections (25%) were the leading causes of death. This research sheds light on leukemia in extra-medullary tissues, uncovers novel clinical-pathological associations, and highlights overlooked therapy side effects, offering insights for future case management. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to examine mortality for people living with dementia/mild cognitive impairment who self-harmed. Methods: We conducted a retrospective cohort study in New South Wales, Australia, using data ranging from 2001 to 2015. From people who accessed hospital services in the study period, we identified 154,811 people living with dementia/mild cognitive impairment, 28,972 who self-harmed and 1511 who had a record of both dementia/mild cognitive impairment and self-harm. We examined rates, causes and predictors of death for people with dementia/mild cognitive impairment and/or self-harm diagnoses using flexible parametric survival analyses. We explored rates of repeat self-harm in people living with dementia who self-harmed. Results: Circulatory disorders accounted for 32.0% of deaths in people with a living with dementia who self-harmed, followed by neoplasms (14.7%), and mental and behavioural disorders (9.6%). Death was more likely for someone who had self-harmed if they developed dementia/mild cognitive impairment. Predictors of death included male sex, greater physical comorbidity, a history of delirium, more previous emergency department presentations and fewer previous mental health ambulatory service days. Greater engagement with outpatient mental health services predicted a decreased likelihood of repeat self-harm. Discussion: We found that mortality increases when people who self-harm develop dementia. We argue post-diagnosis support offers a potential opportunity to reduce mortality rates in people with both dementia and self-harm diagnoses. [ABSTRACT FROM AUTHOR]

Background: Surgery is an indispensable component of a functional healthcare system. To date there is limited information regarding how many people die during the perioperative period globally. This study describes a protocol for a systematic review and multilevel meta-regression to evaluate time trends regarding the odds of perioperative mortality among adults undergoing a bellweather surgical procedure while accounting for higher order clustering at the national level. Methods: Published studies reporting the number of perioperative deaths from bellweather surgical procedures among adults will be identified from MEDLINE, Embase, Cochrane CENTRAL, LILACS and Global Index Medicus. The primary outcome will be the rate of perioperative mortality across time and the secondary outcome will be investigating cause of death over time as a proportion of overall perioperative mortality. Two reviewers will independently conduct full text screening and extract the data. Disagreements will first be resolved via consensus. If consensus cannot be reached a third reviewer will be included to arbitrate. Due to human resource limitations, a risk of bias appraisal will not be conducted. From the included studies a multilevel meta-regression will be constructed to synthesize the results. This model will conceptualize patients as nested in studies which are in turn nested within countries while taking into account potential confounding variables at all levels. Discussion: The systematic review and multilevel meta-regression that will be conducted based on this protocol will provide synthesized global evidence regarding the trends of perioperative mortality. This eventual study may help policymakers and other key stakeholders with benchmarking surgical safety initiatives as well as identify key gaps in our current understanding of global perioperative mortality. Trial registration: Systematic review registration: PROSPERO registration number 429040. [ABSTRACT FROM AUTHOR]

BACKGROUND: Planetary and human health are highly intertwined; our current food system is associated with high greenhouse gas emissions (GHGE) and burden of disease. OBJECTIVE: The aim of this study was to investigate the associations of diet-related GHGE with all-cause and cause-specific mortality in Japan. METHODS: This study included 58,031 Japanese adults (35,078 women and 22,953 men) 40–79 y of age who participated in the Japan Collaborative Cohort Study during the period 1988–1990. Diet-related GHGE was calculated from dietary intake estimated by a validated food frequency questionnaire and previously developed GHGE tables of each food and beverage. Participants were classified into quintiles of diet-related GHGE per kg food/ d. Hazard ratios (HRs) of all-cause and cause-specific mortality were calculated using the Cox proportional hazard and restricted cubic spline models. Results: The average diet-related GHGE was 1,522??g-CO2-eq/kg?food/d. Over a period of 19.3 y (955,819 person-years) of median follow-up, 11,508 deaths were documented. After adjusting for lifestyle and medical history, in comparison with the fourth quintiles of diet-related GHGE, the first and fifth quintiles were associated with a higher risk of all-cause mortality: multivariable HR of all-cause mortality was 1.11 [95% confidence interval (CI): 1.05, 1.18] and 1.09 (95% CI: 1.03, 1.17) for the lowest and highest GHGE, respectively; those of cardiovascular disease mortality were 1.23 (95% CI: 1.10, 1.38) and 1.22 (95% CI: 1.08, 1.37), respectively. The diet-related GHGE range with the lowest HR of all-cause mortality was 1,400–1,600??g-CO2eq/kg food/d (푝 for nonlinearity <0.001). Replacing one serving of red meat with one serving of pulses was inversely associated with all-cause mortality (HR=0.96; 95% CI: 0.93, 0.99) and GHGE (mean change, -347??g-CO2-eq/kg/d; 95% CI: -353, -342). DISCUSSION: Diet-related GHGE was associated with all-cause and cardiovascular disease mortality in a U-shaped fashion. This finding could be useful for creating a policy for sustainable shifts in dietary habits that will benefit the population and environmental health. [ABSTRACT FROM AUTHOR]

Drowning is one of the hardest homicides to prove. Proof, such as bodies, can be decomposed and washed away, and gathering forensics can be very challenging. Since it is common, police may assume drowning as an accident. Drowning and blunt force injuries are mode extremely combined in complex homicide. We report a difficult case of complex homicide by blunt trauma causing basilar skull fracture in a drowned-suspected corpse. A decomposing body was found in the river with no identifiable injuries visible as the body had decomposed on external examination. In an autopsy is also difficult to identify the cause of death because the internal organs are so badly decomposed. Further autopsy, we obtained the accidental finding that there was a fracture to the base of the skull which was suspected to be due to blunt force trauma. It is hard to know how to search for clues in homicide involving drowning as there is no definitive test to determine that a death was caused by drowning. We concluded that a complex homicide by blunt trauma and drowning that confuses between homicide and accidental death should be thoroughly investigated by autopsy. Even though the internal organs had already decayed and liquefied. [ABSTRACT FROM AUTHOR]

Background This study compared the mortality risk of long-lived siblings with the U.S. population average and their spouse controls, and investigated the leading causes of death and the familial effect in death pattern. Methods In the Long Life Family Study (LLFS), 1 264 proband siblings (mean age 90.1, standard deviation [ SD ] 6.4) and 172 spouses (83.8, 7.2) from 511 U.S.-based families were recruited and followed more than 12 years. Their survival function was compared with a birth cohort-, baseline age-, sex-, and race-matched pseudo sample from U.S. census data. To examine underlying and contributing causes, we examined in detail 338 deaths with complete death adjudication at the University of Pittsburgh Field Center through the year 2018. A familial effect on survival and death patterns was examined using mixed-effect models. Results The LLFS siblings had better survival than the matched U.S. population average. They also had slightly but not significantly better survival than their spouses' (HR = 1.18 [95%CI 0.94–1.49]) after adjusting for age and sex. Age at death ranged from 75 to 104 years, mean 91.4. The leading causes of death were cardiovascular disease (33.1%), dementia (22.2%), and cancer (10.7%). Mixed effect model shows a significant random effect of family in survival, with adjustment of baseline age and sex. There was no significant familial effect in the underlying cause of death or conditions directly contributing to death among siblings recruited by the University of Pittsburgh Field Center. Conclusions Our findings demonstrate a higher survival in the LLFS siblings than the U.S. census data, with a familial component of survival. We did not find significant correspondence in causes of death between siblings within families. [ABSTRACT FROM AUTHOR]

Cardiac arrhythmia is currently considered to be the direct cause of death in a majority of sudden unexplained death (SUD) cases, yet the genetic predisposition and corresponding endophenotypes contributing to SUD remain incompletely understood. In this study, we aimed to investigate the involvement of Coenzyme Q (CoQ) deficiency in SUD. First, we re-analyzed the exome sequencing data of 45 SUD and 151 sudden infant death syndrome (SIDS) cases from our previous studies, focusing on previously overlooked genetic variants in 44 human CoQ deficiency-related genes. A considerable proportion of the SUD (38%) and SIDS (37%) cases were found to harbor rare variants with likely functional effects. Subsequent burden testing, including all rare exonic and untranslated region variants identified in our case cohorts, further confirmed the existence of significant genetic burden. Based on the genetic findings, the influence of CoQ deficiency on electrophysiological and morphological properties was further examined in a mouse model. A significantly prolonged PR interval and an increased occurrence of atrioventricular block were observed in the 4-nitrobenzoate induced CoQ deficiency mouse group, suggesting that CoQ deficiency may predispose individuals to sudden death through an increased risk of cardiac arrhythmia. Overall, our findings suggest that CoQ deficiency-related genes should also be considered in the molecular autopsy of SUD. [ABSTRACT FROM AUTHOR]

Objective: Suicidal thoughts and behaviors are a leading cause of death, injury, and hospitalization among adolescents. Few evidence-based interventions exist, and these tend to be inaccessible for most youth. Electronic safety plan interventions represent a new avenue to disseminate an evidence-based suicide prevention tool. However, it is not clear whether youth find electronic, self-guided safety plans helpful, nor whether they will use the resulting safety card when experiencing suicidal thoughts or urges. This study examines adolescents' perceptions and use of an electronic, self-guided safety plan intervention. Method: We recruited 322 adolescents with a past-year history of suicidal thoughts or behaviors, ages 13–17 (55.9% white and non-Hispanic; majority reporting diverse sexual orientations and genders) online via social media to participate in this two-part longitudinal study. At baseline, participants completed the electronic safety plan interventions and reported on key aspects of its usefulness and areas of improvement. Participants reported their use and perceptions of the plan one month later. Results: Results suggested that adolescents understood, liked, and believed they would use a self-guided safety plan. One month later, about ⅓ of youth who experienced suicidal thoughts or urges used their safety card. Open-ended responses highlighted several features that adolescents enjoyed, including clarity, ease of use, and privacy. Participants also highlighted key areas for improvement, including formatting and language. Conclusion: This study provides initial support for adolescent use of electronic self-guided safety plans. Next steps include updating this intervention based on youth feedback and testing the effectiveness of this tool using gold standard research methods. [ABSTRACT FROM AUTHOR]

Background: There is no specified diagnostic procedure that can help in determining the cause of death and the diagnosis of drowning because the pathohistological signs are almost identical and non-specified. Aim: Our study aims to recognize and prove diatom appearance in organs from a forensic aspect in Bosnia and Herzegovina, and to examine which is the more specific method in the diagnosis of drowning, the diatom test or the pathohistological finding. Methods: Rats of the recommended body weight were divided into four groups: G1 (n = 8; mechanism of death--asphyxia; cause of death--suffocation, submerged 1 hour after death); G2 (n = 8: mechanism of death-asphyxia; cause of death-suffocation, immersed 72 hours after death); G3 (n = 8: mechanism of death-asphyxia; cause of death-drowning, autopsy immediately after death), and G4 (n = 8: mechanism of death-asphyxia; cause of death-drowning, post mortem 24 hours after death). Results: During the diatom analysis, four species of diatoms, Diatoma vulgaris, Melosira varians, Epithemia adnata, and Cymbella sp, were successfully recovered from the stomach. Microscopic analysis did not detect diatoms in the kidneys and brains of rats, while the pathohistological changes were relatively uniform. Conclusion: Our results propose that the diatom test is a sustainable tool for supporting the diagnosis of drowning in the forensic pathology analysis of the cause of death. This experimental study is a starting point toward the optimization of tests and sampling in cases of unexplained etiology. [ABSTRACT FROM AUTHOR]

Aims This study described the burden of alcohol-related morbidity and mortality among those who had been enrolled in residential treatment for drug use disorders in Denmark and investigated whether self-reported information on alcohol use provided at treatment admission can be used to assess risk for future serious alcohol-related harms. Methods At baseline (entry in drug use disorder treatment during 2000–10), clients completed a European adaptation of the Addiction Severity Index-5. We tracked 4981 clients through 2018 using multiple national registers to identify fully (100%) alcohol-attributable hospital contacts and deaths. Results The death rate due to fully alcohol-attributable causes was 411 per 100 000 person-years, with an average of 0.18 fully alcohol-attributable hospital contacts per person-year. Using the Addiction Severity Index-5 alcohol composite score as a predictor in an adjusted competing risks regression model, a higher score was associated with a higher risk of alcohol-related death. The alcohol composite score was a significant predictor of alcohol-related hospital contacts in an adjusted recurrent events model. Conclusions A substantial proportion of people originally identified as experiencing drug use disorders have alcohol problems that need to be monitored and managed to prevent serious complications. By demonstrating the predictive power of self-reported data, our study concludes that the Addiction Severity Index-5 can be used to identify individuals with drug use disorders at risk for severe long-term alcohol-related health outcomes. [ABSTRACT FROM AUTHOR]

Sedentary behavior (SB) may affect arterial stiffness, preceding the development of cardiovascular disease. We investigated the association of objectively measured SB with arterial stiffness. We also investigated factors that affected this association. We recruited adult volunteers and measured SB with thigh‐worn accelerometery for 24 hrs/day for eight consecutive days. Central (carotid‐femoral pulse wave velocity, cfPWV, gold standard) and local carotid arterial stiffness (stiffness index Beta and pressure‐strain elasticity EP) were measured with ultrasound. Linear regression was used and adjusted for demographics, cardiometabolic factors, and moderate‐to‐vigorous physical activity (MVPA) volume. Effect modification was studied with interaction terms. Participants (N = 664, 64 (standard deviation: 11, range: 23–89) years, 397 (59.8%) male) demonstrated 9.1 (1.6) hrs/day of SB, and arterial stiffness was 8.6 (3.0) m/s for cfPWV, 6.4 (2.9) for Beta, and 87 (43) kPa for EP. SB was not associated with cfPWV (β = 0.04 95% CI (−0.11, 0.18), p = 0.60). The association of SB with local arterial stiffness was modified by systolic blood pressure (SBP) and MVPA volume. Stratified analyses revealed positive associations of SB with Beta (β = 0.29 (0.05, 0.53), p = 0.016) and EP (β = 4.83 (1.39, 8.27), p = 0.006) in participants with SBP > 134 mmHg or > 103 min/day of MVPA (β = 0.23 (0.03, 0.42), p = 0.024 and β = 3.55 (0.82, 6.29), p = 0.011, respectively). We found no association of objectively measured SB with central arterial stiffness. However, SB was positively associated with local carotid stiffness in participants with higher SBP or MVPA levels. In certain subgroups, SB may affect carotid arterial stiffening, reinforcing the relation between SB and cardiovascular disease. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyse the burden of disease due to noncommunicable diseases (NCDs) between 1990 and 2021 in Brazil. In addition, this study compared mortality from NCDs with mortality from all causes and COVID-19, analysed NCD mortality trends and projections for 2030, and analysed NCD mortality rates and risk factors attributed to these deaths among the 27 states of Brazil. Ecological studies. This study used the Global Burden of Disease study (GBD) database from 1990 to 2021. Premature deaths from four NCDs (neoplasms, cardiovascular disease, chronic respiratory diseases and diabetes mellitus) were analysed. The following metrics were used to analyse the burden of NCDs in Brazil: absolute number of deaths, proportional mortality, mortality rate, years of life lost due to premature death (YLL), years lived with disabilities (YLD) and disability-adjusted years of life lost due to premature death (DALY). For comparison between the years studied and states, age-standardised rates were used. Finding from this study showed that there was increase in the proportion of premature deaths due to NCDs between 1990 and 2019 (29.4 % in 1990, 30.8 % in 2019), and a reduction in 2021 (24.7 %). The mortality rates, DALY and YLL from NCDs declined between 1990 and 2019 (−37.7 %, −34.5 % and −38.3 %, respectively); however, a stability in mortality rates, DALY, YLD, YLL was observed between 2019 and 2021 (−0.1 %, 0.7 %, −0.1 % and 0.8 %, respectively). Between 1990 and 2021, there was a decline in mortality rates, DALY and YLL for most states and an increase in YLD rates. However, results suggest that the Sustainable Development Goal (SDG) for the reduction in mortality from NCDs by one-third by 2030 will not be achieved. The main risk factors associated with premature death from NCDs in 2021 were high blood pressure, tobacco use, dietary risks, high body mass index (BMI) and high blood glucose levels. The correlation between sociodemographic index and percentage change in mortality rates was significant for the following total NCDs, cardiovascular disease, chronic respiratory disease, diabetes and neoplasms. The current study highlights the importance of deaths from NCDs in Brazil and the worsening of mortality rates since 2016, as a result of austerity measures and the COVID-19 pandemic, which compromises the achievement of the SDG reduced mortality targets for NCDs. There was a reduction in risk factors for NCDs, mainly behavioural, although metabolic risk factors are of great concern and require new strategies to promote health, prevention and comprehensive care. [ABSTRACT FROM AUTHOR]

This study aims to analyse age-specific all-cause mortality trends in the UK before and after COVID-19 emergence to determine if pre-pandemic trends contributed to increased mortality levels in the post-pandemic era. Statistical analysis of UK mortality data. We utilised age-structured population and mortality data for all UK countries from 2005 to 2023. Mortality rates were calculated for each age group, and excess mortality was estimated using the Office for National Statistics (ONS) method. Our most concerning finding is an increase in all-cause mortality rates for middle-aged adults (30–54 years) starting around 2012. The COVID-19 pandemic may have further impacted these rates, but the pre-existing upward trend suggests that current elevated mortality rates might have been reached regardless of the pandemic. This finding is more alarming than the slowdown in the decline of cardiovascular disease death rates for individuals under 75 noted by the British Heart Foundation. Our results highlight the importance of considering both immediate pandemic impacts and long-term mortality trends in public health strategies. This underscores the need for targeted interventions and improved healthcare planning to address both ongoing and future challenges. [ABSTRACT FROM AUTHOR]

To describe analgesic-related deaths in France and report trends over a 10-year period. The DTA ("Décès Toxiques par Antalgiques") register is a French database of analgesic-related deaths among people without a history of drug abuse, reported by forensic toxicology experts. We included analgesic-related deaths occurring from January 2013 to December 2022 in France. Subject demographic characteristics and medical history, forensic autopsy findings, and toxicology reports were evaluated. Among the 1036 deceased individuals (mean [SD] age, 48.3 [15.6] years), there were slightly more women than men (M:F sex ratio, 0.89:1). Over the entire study period, tramadol was the leading cause of death, ahead of morphine. A relative increase in oxycodone-related mortality was observed (from 6.8% in 2013 to 21.1% in 2022) compared to a progressive decrease in tramadol, morphine, and codeine-related deaths (from 43.2%, 31.1% and 24.3% in 2013 to 37.5%, 26.6% and 20.3% in 2022, respectively). However, no statistically significant variations were found (Chi-squared tests of homogeneity). Other analgesics (buprenorphine, dihydrocodeine, fentanyl, gabapentin, ketamine, methadone, nefopam, and pregabalin) were also implicated in deaths, but with low and stable rates over the period studied. In France, no increase in fentanyl-related deaths and only a non-significant increase in oxycodone-related deaths were observed over the period 2013–2022. Tramadol was the leading cause of analgesic-related deaths throughout this period. Although close monitoring is still required, particularly for oxycodone, our data do not support the hypothesis of an opioid crisis in France. [ABSTRACT FROM AUTHOR]

The objective of this study was to provide novel comparative insights on the contributions of injury deaths to the changes in sex gaps in life expectancy (SGLE) and sex gaps in life disparity (SGLD) across Nordic countries. Retrospective demographic analysis of aggregated mortality data. To compute life expectancy (LE)/life disparity (LD), annual data on age- and sex-specific causes of death from the World Health Organization mortality database were used to construct abridged life tables for two periods: 2000–2002 and 2016–2018 (2014–2016 for Norway). The contributions of injury deaths to the changes in the SGLE and SGLD between these two periods were decomposed by age and cause using a continuous-change model. Females' LE and LD advantages due to injury deaths narrowed by 0.16–0.44 (0.06–0.35) years for LE (LD) over time. While self-inflicted injuries consistently played a predominant role in contributing to the SGLE/SGLD in all countries in both periods, in all countries but Finland, transport accidents had the greatest contributions to the narrowing SGLE/SGLD. Widening SGLE due to self-inflicted injuries in Iceland and due to falls in Sweden were unique to these countries. Accounting for >20% of total contributions of injury deaths, the age group of 20–24 years had the greatest contributions to the narrowing SGLE/SGLD. Deaths due to falls in older ages and assault in younger ages generally contributed to the widening SGLE/SGLD. Injury deaths, particularly transport accidents, contributed significantly to the narrowing SGLE and SGLD across Nordic countries, with cross-country variations in age- and cause-specific patterns. The results suggest the need for injury prevention policies targeting self-inflicted injuries in younger and falls in older males. [ABSTRACT FROM AUTHOR]

This study assessed associations of three theoretically different occupational class schemes with all-cause and cardiovascular mortality in Norwegian men and women. Pooled survey and register data from four Norwegian cohort studies. We pooled survey data from four general population cohorts (N = 97,469) linked to national mortality registries with follow-up over 45 years. Survival was modelled using accelerated failure time models stratified by sex for three class schemes: The European Socio-Economic Classification (ESeC), The Oslo Register Data Class scheme (ORDC) and The International Socio-Economic Index (ISEI). Main analyses were adjusted for age, birth cohort, and study. Secondary analyses included smoking behaviour as a mediator. During median 27.6 years of observation, 37,488 participants had died (13,243 from cardiovascular disease). Hazard ratios for male all-cause mortality were lowest in the highest occupational class categories ORDC 2: 0.68 (0.65–0.72), ESeC 1: 0.76 (0.73–0.79) and ISEI 5th quintile: 0.80 (0.77–0.82) compared to working class reference categories. Female mortality risks were lowest for Cultural Lower Middle class ORDC 7: 0.84 (0.72–0.98), Small Employers and Self-employed ESeC4: 0.70 (0.50–0.97) and ISEI 5th quintile: 0.79 (0.70–0.90). Patterns for cardiovascular mortality were similar to all-cause mortality. Including smoking behaviour as a mediator attenuated associations, but overall mortality patterns according to occupational class remained unchanged. The results underline that mortality inequalities do not simply consist of higher risks in the most disadvantaged groups. The association of occupational class with mortality is found across different categories of occupational class schemes, illustrating their continued relevance for studying social determinants of health. [ABSTRACT FROM AUTHOR]

To assess all-cause mortality and suicides after pediatric traumatic brain injury (pTBI). We conducted population-based historical cohort study using three nationwide registers from 1998 to 2018 in Finland. All patients that were the age of 0–17 at the time of the pTBI were included. The reference group consisted of children with ankle or wrist fractures. We used Kaplan–Meier and restricted mean survival time (RMST) analysis with 95% confidence intervals (CI) to compare all-cause mortality and suicides between groups. After 20 years of follow-up, there were 479 deaths in the pTBI group (0.67% of 71,963) and 306 deaths in the reference group (0.47% of 64,848). In the pTBI group, 28.6% of the deaths occurred after the first follow-up year, compared to 2.6% in the reference group. In all-cause mortality, survival time was slightly less in the pTBI group with age and gender adjustment throughout the follow-up period [20-year RMST ratio: 0.995; CI (0.994–0.996)]. The leading manners of death were suicides (pTBI group = 28.4%; reference group = 45.5%) and traffic collisions (pTBI group = 37.4%; reference group = 20.8%). Age and gender-adjusted survival time was slightly less for those with suicide as a manner of death in the pTBI group [10-year RMST ratio: 0.999; CI (0.999–0.999); 20-year RMST ratio: 0.999; CI (0.998–0.999)]. Children and adolescents who sustained a TBI have slightly lower long-term survival time for all-cause mortality, most of which occurs during the first year following injury. There is no clinically meaningful difference in deaths by suicide between the two injury groups. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore sex-specific disparities in rates of deaths of despair across 183 countries from 2000 to 2019. Secondary analysis of cross-sectional population-level data. Data were obtained from the World Health Organization Health Inequality Data Repository. We analysed data on mortality due to alcohol, drug-use disorders, and self-harm (as a proxy for suicide). We calculated the average rate of deaths of despair by year and sex, trends in these rates, and cause-specific mortality trends. We then fitted mixed-effect generalised linear models to compare mortality rates by sex and country. Analyses revealed significant disparities by sex, with a 3.3-fold higher rate among men than among women globally (95% confidence interval: 3.1–3.5, P < 0.001). There was a significant decline in deaths of despair globally and among both sexes during the assessed period (5% per 5 years). Lesotho, Belarus, the US, the Russian Federation, Guyana, and Slovenia ranked among the top 10 countries out of 183 with the highest mortality rates for both sexes. Canada, the Republic of Korea, Belgium, and Finland were countries with the highest mortality rates among women, whereas Ukraine, Lithuania, Mongolia, and Eswatini have the highest rates among men. In the US, 5-year mortality rates increased by 35% for women and 21% for men: drug-use mortality showed a significant increase over time, whereas suicide rates decreased for both sexes in the given country. Additionally, mortality rates from alcohol use decreased among women. This global analysis shed light on health disparities by sex in deaths of despair, especially concerning trends in the US. It identified countries and groups in need of targeted mental health and substance-use programs. Moreover, the disparities by sex revealed in this analysis suggest that mental health and substance-use interventions and programs may need to be more attentive to sex and/or gender, such as inequitable social norms and restrictive forms of masculinities, which have been shown to be contributing factors to deaths of despair. [ABSTRACT FROM AUTHOR]

Despite extensive public health initiatives, Bulgaria still has the lowest life expectancy at birth (LE) in the European Union. Sex and ethnic differences in LE and mortality are also exceptionally large. We aimed to identify what causes of death drive these wide disparities and thus provide clear targets for future public health interventions. We conducted a retrospective analysis of mortality rates from 2010 to 2022 to assess sex disparities in LE by age and cause of death. Combining mortality data with the 2021 Bulgarian census also allowed us to study LE disparities among the three main ethnic groups (Bulgarians, Turks, and Roma). We implemented standard demographic decomposition methods to quantify the role of seven major causes of death on LE disparities. We found that the difference between male and female LE has persisted for around seven years. Circulatory diseases contribute 3.66 years, or around 50% of the male-female gap. Ethnic LE disparities are larger for women than for men. Circulatory diseases account for more than 60% of these ethnic LE gaps. COVID-19 mortality explained between 0.5 and 1.1 years of the male-female gap. We found minimal differences in COVID-19 mortality across ethnic groups in Bulgaria. In Bulgaria, circulatory diseases contributed more to both the sex and ethnic LE gaps than in any other previously studied country. Our findings suggest that future public health policy initiatives should focus on circulatory diseases to narrow the Bulgarian LE disparities. One possible target for such a policy would be to reduce excessive smoking and alcohol consumption. [ABSTRACT FROM AUTHOR]

Background: De novo malignancies are one of the leading causes of death after liver transplantation (LT), particularly in patients transplanted for alcohol‐related liver disease (ALD). This retrospective study aimed to assess risk factors for malignancies and to evaluate the impact of calcineurin inhibitor (CNI) discontinuation. Methods: From 1990 to 2015, all patients transplanted for ALD were included. Results: A total of 493 patients were included, 77.9% were male and the median age at LT was 54 years. After LT, 278 de novo malignancies were diagnosed in 214 patients (43.4%). The cumulative incidence of de novo malignancies was 16.3% at 5 years, 34.4% at 10 years, and 49.8% at 15 years. In multivariate analysis, the independent risk factors were male gender (HR = 1.6), and active or weaned smoking (HR = 2.0). Discontinuation of CNI was a protective factor (HR = 0.6). Survival after diagnosis of de novo malignancy was 42.7% at 5 years and 27.5% at 10 years. Conclusion: Our results confirm the major incidence of de novo malignancies after LT for ALD, as well as the important role of non‐modifiable risk factors such as smoking and gender. CNI discontinuation is a protective factor, and the only adaptable, and could be proposed in smoker male patients transplanted for ALD. [ABSTRACT FROM AUTHOR]

Tuberculosis is the primary cause of death due to infection in the world. Identification of Mycobacterium tuberculosis in sputum is a diagnostic test, which can be used in screening programs—especially in countries with a high incidence of tuberculosis—to identify and treat those persons with the highest risk of disseminating the infection. We previously developed an algorithm which is able to automatically detect mycobacteria on tissue; in particular, our algorithm identified acid-fast bacilli on tissue with 100% specificity, 95.65% sensitivity, and 98.33% accuracy. We tested this algorithm on 1059 Ziehl–Neelsen-stained sputum smears to evaluate its results as a possible tool for screening. The results were displayed as a heat map of 32 × 32 pixel patches. Analysis of the positive patches revealed a good specificity (86.84%) and 100% sensitivity for patches with a level of confidence over 90; furthermore, the accuracy remained over 95% for all levels of confidence over 80, except the class (95–100]. The modest specificity is caused by the peculiarities of smears (uneven thickness, dust contamination, lack of coverslip). We will train the algorithm on sputum smears to increase the specificity to over 95%. However, as our algorithm showed no false negatives, it is suitable for screening. [ABSTRACT FROM AUTHOR]

The French "OMIN registry" was established in 2015 to collect nationwide standardised data concerning biological, clinical, environmental and social characteristics of sudden unexpected death in infancy (SUDI) and unexpected death in children aged 1–2 years. A biobank has existed since July 2020 to store biological samples for each case. This article aimed to detail (1) a brief history and the objectives of the registry; (2) a description of the methodology used; (3) the first results of the registry, i.e. the main characteristics of the cases included so far; (4) the process for accessing the data for research projects; and (5) issues regarding weakness and improvement and perspectives offered by the registry. On 31 May 2024, 1975 cases were included in the OMIN registry; on 31 December 2022, 4606 biological samples from 176 cases were collected. For each deceased child, different types of data are registered on an electronic case report form: socio-demographic data, personal and familial medical background, environment and feeding data, clinical data, and biological and imaging results. A strict and continuous quality control process is used to ensure the reliability of the data, in parallel with specific actions to improve the exhaustiveness of the registry. The OMIN registry database is one of the largest and the most complete databases on SUDI, especially in Europe, and the first in the world to associate a standardised biological sample collection with it. Perspectives of research provided by our registry are numerous and could be supported by national and international scientific collaborations. Conclusion: This article details the objectives and methods of the French registry of SUDI. It provides initial results relating to the population included in the register and the procedure for accessing the data. What is Known: • In Western Europe, France is one of the countries with the highest SUDI rate, making it the first cause of death of infants between 28 and 364 days. • The development of epidemiological tools on a national and international scale is essential to advance research into the determinants and risk factors of unexpected death in children under 2 years of age. What is New: • The OMIN registry was created in France in 2015 to collect nationwide standardised social, environmental, clinical, and paraclinical data for cases of unexpected death in children aged 0 to 2 years. • To date, the OMIN registry has included 680 data from almost 2000 children unexpectedly deceased, completed by a biocollection since 2020. • Data from the OMIN registry, unique in its field, are freely available for scientific research teams, after acceptation by the scientific committee of the registry. [ABSTRACT FROM AUTHOR]

Background: Cancer is one of the leading causes of death worldwide. The tumor microenvironment makes the tumor difficult to treat, favoring drug resistance and the formation of metastases, resulting in death. Methods: Stimuli-responsive nanoparticles have shown great capacity to be used as a powerful strategy for cancer treatment, diagnostic, as well as theranostic. Nanocarriers are not only able to respond to internal stimuli such as oxidative stress, weakly acidic pH, high temperature, and the high expression of particular enzymes, but also to external stimuli such as light and paramagnetic characteristics to be exploited. Results: In this work, stimulus-responsive nanocarriers functionalized with arginine-glycine-aspartic acid (Arg-Gly-Asp) sequence as well as mimetic sequences with the capability to recognize integrin receptors are analyzed. Conclusions: This review highlights the progress that has been made in the development of new nanocarriers, capable of responding to endogenous and exogenous stimuli essential to combat cancer. [ABSTRACT FROM AUTHOR]

In addition to being the main cause of death and premature mortality In Europe, cardiovascular diseases are Increasingly becoming a significant burden on public health, productivity and healthcare resources. At 34%, coronary heart disease (CHD) represents the largest proportion of this spectrum (1). The traditional understanding of CHD, which focused almost exclusively on epicardial atherosclerotic stenoses, Is now considered outdated. Although increasing attention Is being paid to non-obstructive CAD, the mechanisms are largely unknown and the diagnosis may be underestimated in everyday practice. Therefore, itls crucial to recognize non-obstructive CHD in order to develop appropriate treatment strategies. The aim of this review Is to provide an overview of the common definitions, causes and diagnostic steps of non-obstructive coronary artery disease. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancers are still the leading cause of death worldwide. This is related, among other things, to the non-specific symptoms, especially in the initial stages, and also to the limited possibilities for treatment. Therefore, research is still being conducted to improve the detection of this type of cancer and increase the effectiveness of therapy. The potential application of natural compounds in cancer management deserves special attention. In the group of such products, there are polyphenolic compounds that reveal, e.g., anti-oxidative, anti-carcinogenic, anti-inflammatory, anti-diabetic, and neuroprotective properties. One of these polyphenols is rosmarinic acid, commonly found in plants such as the Boraginaceae and Nepetoideae subfamilies of the Lamiaceae (mint) family. A number of studies have considered the positive effects of rosmarinic acid in the treatment of many cancers, including gastrointestinal ones such as oral, stomach, pancreas, colon, and liver cancers. The main aim of this paper was to summarize the mechanisms of action of rosmarinic acid in gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Cancer is one of the most common causes of death in the world. Despite the fact that there are many types of therapies available, cancer treatment remains a major challenge. The main reason for the ineffectiveness of chemotherapy is the acquisition of multidrug resistance (MDR) by cancer cells. One of the factors responsible for the acquisition of MDR is the NRF2 transcription factor, which regulates the expression of proteins such as HO-1, NQO1, MRP1, MRP2, and GST. In normal cells, NRF2 is the first line of defense against oxidative stress, thereby preventing carcinogenesis. Still, its hyperactivation in cancer cells causes them to acquire MDR, which significantly reduces or eliminates the effectiveness of chemotherapy. Considering the important role NRF2 plays in the acquisition of MDR, its modulators and, above all, inhibitors are being sought after, including among compounds of plant origin. NRF2 inhibition may prove to be a key element of anticancer therapy. This review summarizes the current state of knowledge about plant NRF2 inhibitors and presents the effects of their use in overcoming MDR in cancer. [ABSTRACT FROM AUTHOR]

Background & objectives Cancer is one of the leading causes of death among older adults worldwide. The global burden of cancer among older individuals is increasing due to the ageing population. The increasing burden of cancer among older adults will pose significant social and economic challenges for the delivery of healthcare services. Materials Estimated cancer new cases, deaths, age-standardized truncated incidence and mortality rate per 100,000 for older adults (60 yr or above) were reported using GLOBOCAN 2020 estimates (gco.iarc.fr). Mortality to Incidence ratio (M/I ratio) expressed in percentage by gender and continent was provided. Results Globally, of all cancer cases, 11.3 million cases (representing 62.3%) and 7.5 million deaths (representing 71.2%) were seen among older adults. The top five leading sites of cancer account for 62.2 per cent of older men and 55.9 per cent of older women; however, a widespread geographical variation across world regions is observed. The number of new cancer cases among older adults is expected to rise from 11.3 to 19.8 million (a 75.2% increase) and deaths from 3.99 to 7.3 million (82.8% increase) by 2040. Interpretation & conclusions The expected rise will bring exceptional challenges to healthcare systems, especially in lower- or lower-medium-income countries where resources are limited. Data on cancer among older adults will help health planners and policymakers develop global geriatric cancer control policies. [ABSTRACT FROM AUTHOR]

The COVID-19 global pandemic drastically changed the lives of so many, including creating a sense of mass bereavement in the United States because of the million plus lives lost. As obituaries provide public documentation of personal legacies as well as serve to create a generational memory, this study sought to determine how obituaries, published in the United States during a public health crisis with excess deaths, discuss living and dying. We analysed 82 obituaries published in the United States during the COVID-19 pandemic to determine their functions during this time. These U.S. obituaries documented how the COVID-19 pandemic interrupted the life stories of so many. Several key themes emerged in the obituaries – cause of death, COVID-19 changing lives, resilience/positivity, political statements, and thanking healthcare workers. These COVID-19 obituaries shared many of the known functions of obituaries, but they also served as public service death announcements. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of death. Quinoline is well known as one of the most potent pharmaceutically active scaffolds with remarkable pharmacological properties. So, in this article, we focused our efforts on the utility of the key scaffold N′-(1-(4-((7-chloroquinolin-4-yl)amino)phenyl)ethylidene)-2-cyanoacetohydrazide (5) in the synthesis of their novel heterocyclic compounds with potential as anticancer agents. Based on these preliminary screening results against four different human cancer cell lines (HepG2, MCF-7, HCT-116, and PC-3). Gratifyingly, compounds 9 and 16 showed the highest anticancer activity. Adenosine A2B receptor (A2BAR) was found to be the probable cellular target for both promising candidate compounds 9 and 16. The docking study of tested compounds 9 and 16 revealed that they bind more strongly to the A2BAR as compared to that of its co-crystalized ligand, suggesting that the anticancer activities of the tested compounds may be related to their ability to block the A2BAR receptor signaling in cancer cells, leading to cell death. Computational studies and countersurfaces of the novel compounds helped us clarify and interpret the compounds that have high and low anticancer activity. Noteworthy, the results of these studies are approximately compatible with what was done in vitro. [ABSTRACT FROM AUTHOR]

Despite remarkable advances in immunotherapy, melanoma remains a significant cause of cancer mortality. Many factors concerning melanoma mortality are poorly understood, posing an obstacle to optimal care. We conducted a retrospective observational cohort study of 183 patients with metastatic melanoma who died following immunotherapy treatment to investigate sites of metastases at death, settings of death, and mechanisms of death. The median time from metastatic diagnosis to death was 16.1 months (range 0.3–135.1 months). Most patients experienced hospitalization within 3 months before death (80.3%), with 31.7% dying while hospitalized, 31.2% while in inpatient hospice, and 29.4% while in home hospice. The most common sites of metastases at death were distant lymph nodes (62.8%), lung (57.9%), liver (50.8%), brain (38.8%), and bone (37.7%). The most common causes of death were progressive failure to thrive (57.5%), respiratory failure (22.4%), and infection (21.8%); the vast majority (87.9%) of patients died from melanoma‐specific causes. Overall, 10.9% of patients in our cohort had survival >5 years after metastatic diagnosis, and 76.2% of long‐term survivors died due to melanoma. This study describes factors associated with melanoma mortality, highlighting an ongoing need for therapeutic advancements. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to compare outcomes post‐admission to a Swedish paediatric intensive care unit (PICU) in children with complex chronic conditions (CCC) and without CCC. Methods: In this observational registry‐based study, consecutive admissions to the Astrid Lindgren Children's Hospital PICU from 1 January 2008 to 31 December 2016 were analysed. Data on demographics, predicted death rates (PDR), admission diagnoses and causes of death were collected. Mortality was recorded up to 15 years after admission and compared between groups. Results: Patients with CCC constituted 64.6% (n = 3026) of PICU admissions and 83.5% (n = 111) of PICU deaths. The crude mortality rate in PICU was 2.84% overall. CCC‐patients were 2.83 times more likely to die in PICU compared to non‐CCC (OR 2.83; 95% CI: 1.78–4.49). Mortality increased in the CCC‐cohort up to 5 years after PICU discharge, while non‐CCC patients generally survived if they survived in PICU. Of the patients who died in PICU, the median PDR was 22.9% for CCC‐patients and 66.5% in the non‐CCC cohort. Conclusion: Children with CCC accounted for most admissions and deaths in PICU. Despite lower severity of illness scores upon admission, CCC patients were nearly three times more likely to die in PICU compared to non‐CCC patients. [ABSTRACT FROM AUTHOR]

Suicide remains a leading cause of death in the United States, and recent data suggest suicide deaths involving opioids are increasing. Given unprecedented increases in drug-poisoning deaths, suicidality, and suicide deaths in recent years, an updated examination of the trends in suicide deaths involving opioids is warranted. In this descriptive epidemiologic analysis, we leverage final and provisional mortality data from the US Centers for Disease Control and Prevention's WONDER database to examine trends in suicide deaths involving opioid poisoning from 1999 to 2021 by biological sex. Results reveal complex changes over time: the number and age-adjusted rate of suicide deaths involving opioid poisoning among male and female residents tended to track together, and both increased through 2010, but then diverged, with the number and rate of suicide deaths involving opioid poisoning among female residents outpacing that of male residents. However, the number and rate of suicide deaths involving opioid poisoning among male residents then began to stabilize, while that of female residents declined, closing the sex-based gap. Across all years of data, the proportion of suicide deaths that involved opioid poisoning was consistently higher among female decedents (5.8%-11.0%) compared with male decedents (1.4%-2.8%). Findings have implications for improved suicide prevention and harm reduction efforts. This article is part of a Special Collection on Mental Health. [ABSTRACT FROM AUTHOR]

High and low daily ambient temperatures are associated with higher mortality in the general population. People experiencing homelessness (PEH) are thought to be particularly vulnerable, but there is almost no direct evidence available. We examined the temperature-mortality association among PEH in 2 populous, urban counties in hot-climate regions of the United States, focusing on heat effects. Study setting was Los Angeles County, CA, and Clark County, NV, which encompass the cities of Los Angeles and Las Vegas, respectively. Outcomes were 2015-2022 deaths among decedents categorized as homeless in county administrative records. We used quasi-Poisson distributed lag nonlinear models to estimate the association of mortality with daily temperatures and with 7-day lagged temperatures, adjusting for day of week, seasonality, and long-term trends. We estimated the minimum mortality temperature and fraction of mortality attributable to temperatures above and below minimum mortality temperature. The association between daily temperature and PEH mortality was skewed towards greater risk at higher temperatures, especially in Clark County. Temperature-attributable mortality equaled 50.1% of deaths in Clark County (95% CI, 29.0-62.8) and 7.0% in Los Angeles County (95% CI, 1.4-12.1). In both counties, most temperature-attributable deaths were attributable to heat rather than cold. In these hot-climate urban counties, our estimates of heat-attributable mortality among PEH were orders of magnitude greater than those reported in prior research on the general population. These results indicate that temperature vulnerability, particularly heat vulnerability, requires stronger public health and policy responses. This article is part of a Special Collection on Environmental Epidemiology. [ABSTRACT FROM AUTHOR]

Firearm-related violence is the leading cause of death for adolescents and can have lifelong ramifications, including to one's mental health and well-being. Through a scoping review of existing literature published since 1980, the current study describes nuanced pathways through which exposure to firearm violence (direct or indirect) can contribute to the development and exacerbation of posttraumatic symptomatology during adolescence (ages 10–19). Furthermore, this review explores moderators and mediators of this relationship, shedding light on the interplay between individual, familial, and societal factors. Findings from the reviewed studies (N = 16) demonstrate various links between direct and indirect firearm exposure and short- and long-term posttraumatic symptomatology in adolescents and point to necessary solutions that encompass consistent firearm violence prevention and mental health support. Results can inform future research, policy development, and intervention strategies to mitigate the adverse psychological effects of firearm violence on the vulnerable adolescent population. [ABSTRACT FROM AUTHOR]

Aim: The impact of cognitive dysfunction‐associated activities of daily living (ADL) on mortality and rehospitalization for heart failure has not yet been evaluated. Methods: We retrospectively evaluated DASC‐21, the incidence of all‐cause mortality, and rehospitalization for heart failure after discharge in 329 older patients with heart failure. Results: The mean age was 85.1 ± 7.4 years (62.6% women). There were 110 cases of death from any cause (33.4%) during 25.5 ± 16.1 months of follow‐up and 166 cases of rehospitalization from heart failure (50.5%) during 16.1 ± 15.2 months of follow‐up. The DASC‐21 score was not significantly associated with an increased risk of all‐cause mortality or rehospitalization. For each item of the DASC‐21 questionnaire, defective route‐finding (item 6) (HR = 2.631, P = 0.003), common sense and capacity for judgement (item 9) (HR = 1.717, P = 0.040), instrumental ADL (IADL) for shopping (item 10) (HR = 1.771, P = 0.020), and IADL for meal preparation (item 14) (HR = 1.790, P = 0.019) were significantly associated with an increased risk of all‐cause mortality. Disabilities in route finding (HR = 2.257, P = 0.005), IADL for shopping (HR = 1.632, P = 0.016), and IADL for transportation (HR = 1.537, P = 0.033) were significant risk factors for rehospitalization due to heart failure. Even in the multivariate‐adjusted model, disability in defective route‐finding was significantly associated with an increased risk of all‐cause mortality (hazard ratio [HR] = 2.148, 95% confidence interval [CI] 1.090–4.236; P = 0.027) and of rehospitalization for heart failure (HR = 2.138, 95% CI 1.153–3.963, P = 0.016). Conclusions: In older patients hospitalized for heart failure, route disability was associated with all‐cause mortality and rehospitalization for heart failure after discharge. Geriatr Gerontol Int 2024; 24: 1130–1136. [ABSTRACT FROM AUTHOR]

Background: Autopsies are done since the olden days to study anatomy, to learn pathology, and to identify the cause of death. However, this procedure is not widely accepted due to lack of facilities, reluctancies by relatives, various religious and ethical issues, and fear of transmission of communicable diseases. Percutaneous needle autopsies have bridged these shortcomings and provide better results when done under radiological guidance. Aims and Objectives: The aim of the study was to determine the adequacy of tissue obtained by percutaneous needle autopsy in comparison to conventional autopsy for lung and liver tissues. Materials and Methods: Descriptive study, done in autopsies performed in the Department of Forensic Medicine and Department of Pathology, Government Medical College Kottayam. Percutaneous needle samples are obtained from lungs and liver using surface landmarks. Samples are also obtained after opening the deceased body. After microscopic examination, adequacy is observed and morphological findings are compared. Results: In lungs, 164 samples met the adequacy criteria and 156 samples showed similar morphological findings by both methods; in the liver 159 samples met the adequacy criteria and 151 samples showed similar morphological findings by both methods. In lungs and liver, the most common histological finding was congestion. Conclusion: Percutaneous needle autopsies and the tissue thus obtained are adequate and comparable when compared to conventional autopsies. The findings are more comparable in diffuse lesions rather than in localized lesions. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is now one of the top three causes of death worldwide. Despite the availability of various kinds of treatments, there is a paucity of data regarding potential treatment for COPD. Aims and Objectives: This study has been carried out to evaluate the effectiveness and safety of treatments used for COPD. Materials and Methods: A prospective, longitudinal, observational study was carried out at a tertiary care teaching hospital. A total of 105 patients were included and divided into two treatment groups: Group budesonide+formoterol (BF) and group fluticasone+salmeterol (FS) based on the treatment they received. Patients' details were recorded in a pre-defined case record form. Effectiveness was evaluated and compared between the two treatment groups in terms of the number of exacerbations experienced, the mean reduction in COPD assessment test (CAT) score, and the mean change in forced expiratory volume 1 s (FEV1%) at the end of the study period. Safety was assessed by recording adverse drug reactions. Results: Out of a total of 105 patients with COPD, 67 (63.80%) patients belonged to group BF and 38 (36.19%) patients belonged to group FS. Twenty-seven (40.30%) patients from Group BF (n=67) and 18 (47.37%) patients from group FS (n=38) developed exacerbations. No statistically significant difference between group BF and group FS was observed in terms of mean reduction in CAT score (P= 0.17) as well as mean change in FEV1% (P=0.38) from baseline to the end of 6 months of treatment. Conclusion: Our study concludes that inhalational corticosteroids/long-acting beta-agonist combinations such as BF and FS are equally effective in terms of reduction in frequency and severity of exacerbation, reduction in CAT score, and improvement in lung functions (FEV1%). [ABSTRACT FROM AUTHOR]

Background and Objectives: Suicidal ideation (SI) during the postpartum phase is linked with suicide, a leading cause of death during this period. Antenatal depression and anxiety symptoms have both been linked with increased risk for postpartum SI. However, research aimed at examining the relative contributions of antenatal anxiety and depression symptoms towards postpartum SI remains nascent. In this study, we investigated the relative contribution of antenatal anxiety symptoms, depression symptoms, and SI towards postpartum SI. Design: These data are from a longitudinal study in which American mothers were assessed during pregnancy and again at six- to eight weeks postpartum. Methods: Data were analyzed using correlations and logistic regression models. Results: Antenatal anxiety symptoms and antenatal depression symptoms were significantly correlated with postpartum SI. Results from a logistic regression model indicated that antenatal anxiety symptoms (T1; OR = 1.185 [1.125, 1.245], p =.004), but not antenatal depression symptoms (T1; OR = 1.018 [0.943, 1.093], p =.812) or antenatal SI (T1; OR = 1.58 [0.11, 22.29], p = 0.73), were significantly associated with postpartum SI. Conclusions: Antenatal anxiety symptoms, depression symptoms, and SI were positively associated with postpartum SI. When examined simultaneously, anxiety symptoms during the antenatal phase (but not depression symptoms or SI) predicted SI in the postpartum phase. [ABSTRACT FROM AUTHOR]

Background and Purpose : Cancer remains one of the leading causes of death globally. In pursuit of alternative treatments, nature-based ones are especially in demand due to the perceived lesser toxicity and cost-effectiveness. Plumbagin, a naphthoquinone compound derived from the Plumbaginaceae family, has demonstrated significant anticancer properties. It is a yellow crystalline phytochemical that exhibits potent cytotoxic effects against various cancer cells in vitro and in vivo. Results : Its distinct anticancer mechanisms include modulating signaling pathways, such as NF-kβ, STAT3, MMP-9, VEGF, and Akt, induction of apoptosis, autophagy, cell cycle regulation etc. Furthermore, plumbagin also induces reactive oxygen species (ROS) generation and causes oxidative DNA damage. An exciting feature of plumbagin is its ability to sensitize chemo and radio resistant cancer cells. Even with significant anticancer potential, plumbagin is yet to be used in clinics due to its high lipophilicity, insolubility in water, short half-life, and low melting point. To conquer these limitations and possible exploitation of this potent natural compound, the scientific community has used several nano-based delivery systems, such as liposomes, niosomes, micelles, microparticles etc. Conclusion : Despite all these promising attributes, rigorous preclinical and clinical evaluations are essential to validate its actual anticancer potential before considering it as one of the mainstream phytotherapeutic agents. [Display omitted] • The current article is a comprehensive summary of anticancer potential of plumbagin in different cancer models. • The mechanism of action of plumbagin affecting different signaling cascade has been highlighted. • Despite their significant therapeutic potential, plumbagin is yet to be exploited in clinics. The reason and troubleshoot have been suggested. • Various nanoformulations of plumbagin have been covered that showed better efficacy compared to free plumbagin. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study describes characteristics of children ages 1 to 17 years who died of coronavirus disease 2019 (COVID-19) in 2020 to 2022 and whose deaths were reviewed by child death review (CDR) teams across the United States. METHODS: We used data in the National Fatality Review-Case Reporting System to examine children who died of COVID-19. Deaths were determined because of COVID-19 from death certificates or CDR determinations. RESULTS: A total of 183 children 1 to 17 years old who died of COVID-19 were reported in the National Fatality Review-Case Reporting System. One-third (33%) were 15- to 17-year-olds, and 26% were 1- to 4-year-olds. Fifty-six percent were reported as male, 54% white, 24% Black, and 18% Hispanic ethnicity. Physicians declared cause of death in at least 82% of deaths. More than two-thirds (68%) had a medical condition (excluding COVID-19) at time of death. The most common conditions were nervous system disorders (19%), congenital disorders (14%), obesity (12%), respiratory disorders (12%), and neurodevelopmental disorders (10%). Of children with an underlying condition, 35% had 3 or more conditions. Less than half (42%) had contact with a health care provider within a month of their death; and three-fourths died within 14 days of exposure. CONCLUSIONS: This study describes the demographics, death investigation findings, and medical conditions of children who died of COVID-19. The results highlight the short timeline between COVID-19 exposure and death. Pandemic planning that prioritizes prevention efforts and timely access to effective medical care may result in saving children's lives. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Develop guidelines for child death review teams that will improve the consistency in classifying child maltreatment (CM) and distinguish between classification of exposure to hazards and neglect for sleep-related sudden unexpected infant deaths (SUID). METHODS: Sleep-related SUID (n = 25797) were identified from the National Fatality Review-Case Reporting System between 2004 and 2018. Key variables considered when classifying CM among sleep-related SUID were identified. Logistic regression was used to assess the strength of associations and identify factors that distinguished between exposure to hazards and neglect. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Guidelines were developed based on these findings. RESULTS: Among the 13 034 sleep-related SUID with CM identified, hazards in the infant sleep environment were strongly associated with classification of both exposure to hazards and neglect, as were supervisor impairment and child welfare substantiation of the death. Comparing neglect to exposure to hazards, there was no association with sleep environment hazards with ORs ranging from 0.8 to 1.3 (95% CI 0.4-3.0), but sleep-related SUID were approximately twice as likely to be classified as neglect when the supervisor was impaired (OR 2.3, 95% CI 2.0-2.7) or child welfare action was taken (OR 1.8, 95% CI 1.5-2.0). The guidelines recommend classification of exposure to hazards for sleep environment hazards with elevation to neglect if the supervisor was impaired or child welfare substantiated the death. CONCLUSIONS: Among sleep-related SUID, classification of exposure to hazards is based on presence of sleep environment hazards, whereas neglect is based on supervisor impairment and child welfare action. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To describe sudden unexpected infant deaths (SUIDs) occurring in safe sleep environments and explore differences in selected characteristics. METHODS: We examined SUID from 22 jurisdictions from 2011 to 2020 and classified them as unexplained, no unsafe sleep factors (U-NUSF). Data were derived from the Sudden Unexpected Infant Death and Sudden Death in the Young Case Registry, a population-based Centers for Disease Control and Prevention surveillance system built on the National Center for Fatality Review and Prevention's child death review program. SUID classified as U-NUSF included infants who were (1) awake, under supervision, and witnessed to become unresponsive or (2) found unresponsive in a safe sleep environment after sleep (unwitnessed). We calculated frequencies and percentages for demographics, birth and environmental characteristics, medical history, and death investigation findings. RESULTS: Most of the 117 U-NUSF SUID occurred before 4 months of age. Witnessed deaths most commonly occurred at <1 month of age (28%), whereas unwitnessed deaths most commonly occurred at ages 2 to 3 months (44%) Among all U-NUSF, 69% occurred in the infant's home (62% witnessed, 77% unwitnessed). All unwitnessed deaths occurred in a crib; most witnessed deaths occurred while being held (54%) or in a car seat traveling (18%). Most infants (84%) had no history of abuse or neglect. Abnormal autopsy findings were reported in 46% of deaths (49% witnessed, 42% unwitnessed). CONCLUSIONS: Characterizing these deaths is key to advancing our knowledge of SUID etiology. Our study revealed a heterogeneous group of infants, suggesting physiologic, genetic, or environmental etiologies. [ABSTRACT FROM AUTHOR]

The National Fatality Review Case Reporting System (NFR-CRS) is a web-based data collection tool for child death review and fetal and infant mortality review teams. The NFR-CRS captures information from the multidisciplinary review, including the social and community risk factors that may have impacted the death. The NFR-CRS is a nimble data system that has evolved throughout the past 20 years. The most recent enhancements include a life stressors section focused on collecting contextual information such as racism and poverty, revised cause of death sections to better align data collected with risk factors identified in the research, and enhanced data visualizations. The NFR-CRS has improved data quality since the launch of a data quality initiative in 2015. As a result of the data quality initiative, the completeness, consistency, accuracy, and timeliness of the NFR-CRS data have improved. Limitations for the NFR-CRS include the fact that data entered are not population-based, data fields have evolved over time, and there are high percentages of missing and unknown data. Despite its limitations, the NFR-CRS remains a valuable research tool, especially when paired with other data sources. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) have shown comparable efficacy and a superior safety profile in clinical trials for patients with venous thromboembolism (VTE). However, further study is needed to assess DOACs' effectiveness and safety compared to warfarin in a real-world context. Thus, this meta-analysis compares the effectiveness and safety of warfarin and DOACs in patients with VTE. Method: A systematic review of the literature using PubMed and EMBASE was conducted from inception until June 2024. We examined observational studies that compared safety and effectiveness between DOACs and warfarin when used in treating VTE and reported adjusted hazard ratios (HRs) and/or odds ratios (ORs) for recurrent VTE, major bleeding, clinically relevant non-major bleeding, gastrointestinal bleeding, intracranial hemorrhage, and death from any cause. We then estimated the pooled effect using the random-effects model for meta-analysis. Results: A total of 25 studies were included in the current meta-analysis. DOAC therapy was associated with significantly lower risks of recurrent VTE (HR 0.76, 95% confidence interval [CI] 0.69–0.85), major bleeding (HR 0.77, 95% CI 0.72–0.83), clinically relevant non-major bleeding (HR 0.82, 95% CI 0.77–0.88), and gastrointestinal bleeding (HR 0.75, 95% CI 0.68–0.83) compared to warfarin. However, no statistically significant difference was observed in all-cause mortality between the two groups (HR 0.96, 95% CI 0.83–1.10). Conclusion: This meta-analysis found that DOACs are associated with a significant reduction in VTE recurrence in addition to the known favorable safety profile when compared to warfarin. [ABSTRACT FROM AUTHOR]

Purpose: Suicide is a leading cause of death in prison and the suicide rates are several times higher in the prison population than in the general population in most countries. Of the studies that have investigated risk factors for suicide in prison, few have controlled for possible confounding factors. The aim of this study is to identify risk factors of suicide among people in French prisons, over a four-year period. Methods: All incarcerations that occurred in France during 2017–2020 were eligible. Sociodemographic, criminal and prison characteristics were collected for each incarceration from data of the National Prison Service. Survival univariate and multivariate analyses were performed with a Cox regression model. Results: 358,522 incarcerations were included, of which 449 ended in suicide during the follow-up. The median length of prison stay was 5.1 months. The median age at prison entry was 30 years and 95.8% of incarcerations involved men. The overall suicide rate was 173 [157–189] per 100,000 person-years. Factors associated with suicide in the multivariate model (p < 0.05) were the early stage of incarceration and in particular the first week (HR = 7.6 [5.4–10.8]), violent offences and in particular homicide (HR = 3.0 [2.1–4.2]), French (HR = 1.7 [1.2–2.4]) and other European nationalities (HR = 2.1 [1.4–3.3]), age above 40 (HR = 2.0 [1.5–2.6]), pre-trial incarceration (HR = 1.8 [1.4–2.3]), being separated (HR = 1.6 [1.1–2.3] and having a high school diploma (HR = 1.4 [1.0–1.8]). Conclusions: Factors associated with suicide in prison are complex and involve individuals' criminal history as well as conditions of incarceration. These characteristics may be relevant to focus suicide prevention efforts. [ABSTRACT FROM AUTHOR]

Background: For the initial treatment strategy for patients with cardiac resynchronization therapy (CRT) indications, whether to choose left bundle branch area pacing (LBBaP) or biventricular pacing (BVP) remains controversial. We aimed to investigate the cost‐effectiveness ratio (CER) of LBBaP and BVP in heart failure (HF) patients with left bundle branch block (LBBB). Methods: This observational study included HF patients with LBBB who underwent successful LBBaP or BVP. The primary outcomes were echocardiographic response (left ventricular ejection fraction [LVEF] increase ≥5%), LVEF improvement, hospitalization costs, and CER (CER = cost/echocardiographic response rate). Secondary outcomes included other echocardiographic parameters, New York Heart Association (NYHA), N‐terminal pro–B‐type natriuretic peptide (NT‐proBNP), pacemaker parameters, complications, ventricular arrhythmia (VA) events, HF hospitalization (HFH), and all‐cause mortality. Results: A total of 130 patients (85 LBBaP and 45 BVP) were included (65.6 ± 10.0 years, 70.77% men). The median follow‐up period was 16(12,30), months. Compared with BVP, the LBBaP group showed a greater increase in LVEF (20.2% ± 11.8% vs. 10.5% ± 13.9%; p < 0.001), higher echocardiographic response rate (86.1% vs. 57.8%; p < 0.001), and lower hospitalization costs [$9707.7 (7751.2, 18,088.5) vs. $20,046.1 (18,840.1, 22,447.3); p < 0.0001]. The CER was 112.7 and 346.8 in LBBaP and BVP, respectively. The incremental cost‐effectiveness ratio (ICER = △cost/△echocardiographic response rate) was $−365.3/per 1% increase in effectiveness. LBBaP improved cardiac function more significantly than BVP. There were no significant differences in clinical outcomes. Conclusions: LBBaP‐CRT is more cost‐effective than BVP, offering greater LVEF improvement, higher echocardiographic response rates, lower hospitalization costs, and more significantly improved cardiac function. These findings need large randomized clinical trials for further confirmation. [ABSTRACT FROM AUTHOR]

Background: Nonischemic cardiomyopathy (NICM) is responsible for approximately one‐third of heart failure and is associated with significant morbidity and mortality. Recent data suggested the lack of mortality reduction from adding a defibrillator to cardiac resynchronization therapy (CRT) in all patients with NICM. Myocardial fibrosis detected by cardiac magnetic resonance late gadolinium enhancement (CMR‐LGE) can help risk stratify patients who would benefit from adding a defibrillator to CRT in this patient population. Objectives: We aim to assess the relationship between the presence of myocardial fibrosis detected by CMR‐LGE and the rate of major arrhythmic events (MAE) that included sustained ventricular tachycardia (VT), appropriate cardiac resynchronization therapy‐defibrillator (CRT‐D) intervention, ventricular fibrillation (VF), and sudden cardiac death (SCD) in patients with NICM undergoing CRT and to compare all‐cause mortality and heart failure improvement between patients receiving cardiac resynchronization therapy‐pacing (CRT‐P) versus those receiving CRT‐D based on the presence of myocardial fibrosis. Methods: All consecutive patients with NICM satisfying a guideline‐directed indication for CRT implantation were included in the study after excluding patients who refused to consent, patients with acute decompensated heart failure, and those contraindicated for a cardiac magnetic resonance (CMR). Patients were divided into two groups based on the presence of fibrosis in cardiac MRI: the LGE/CRT‐D group and the No LGE/CRT‐P group. They were then followed for 1 year. Results: Sixty patients were enrolled. Sixteen patients (26.6%) developed MAE during the study duration, among those patients, seven had myocardial fibrosis (receiving CRT‐D as per protocol), while nine had no myocardial fibrosis (receiving CRT‐P as per protocol), (41.2% vs. 20.9%, p = 0.045). The presence of CMR‐LGE, regardless of the extent and distribution, predicted MAE with an odds ratio of 2.6 (CI = 1.78–8.9, p = 0.04). The presence of ≥7.5% of myocardial fibrosis by CMR was associated with 54% sensitivity and 100% specificity for MAE in the study population. All‐cause mortality was significantly higher in the No LGE/CRT‐P group versus the LGE/CRT‐D group (15 [34.9%] vs. 2 [11.8%], p = 0.076). Conclusion: In patients with NICM candidates for biventricular pacing, the presence of LGE on CMR, irrespective of the extent or segmental pattern, is independently associated with an MAE and is associated with worse heart failure outcomes. However, the absence of LGE did not rule out MAE, and implanting CRT‐P based on lack of fibrosis may result in higher all‐cause mortality. [ABSTRACT FROM AUTHOR]

Background: Recent studies have demonstrated an obesity paradox, where obese patients with cardiovascular disease have a better outcome compared to those with normal weight. However, the effect of obesity and body mass index (BMI) on the outcome of patients with cardiac resynchronization therapy (CRT) devices remains unclear. The current study aims to investigate this relationship using all available published data. Methods: We systematically reviewed studies from Medline and EMBASE databases from inception to January 2024. Eligible studies must investigate the association between BMI status and all‐cause mortality in individuals with CRT devices. Relative risk (RR) or hazard ratio (HR) and 95% CIs were retrieved from each study and combined using the generic inverse variance method. Results: A total of 12 cohort studies were included in the meta‐analysis. Pooled analysis showed that overweight and obesity patients had lower all‐cause mortality compared to those with normal body weight with the pooled risk ratios (RR) for overweight of 0.77 (95% CI 0.69–0.87, I2 47%) and for obesity of 0.81 (95% CI 0.67–0.97, I2 59%). Conversely, the underweight exhibited higher all‐cause mortality than the group with normal weight, with a pooled RR of 1.37 (95% CI 1.14–1.64, I2 0%). Additionally, higher BMI as continuous data was associated with decreased all‐cause mortality, with a pooled HR of 0.94 (95% CI 0.89–0.98, I2 72%). Conclusions: The pooled analyses observed an obesity paradox in patients with CRT, where overweight and obesity were associated with reduced all‐cause mortality, while underweight individuals exhibited higher all‐cause mortality. Further research is necessary to investigate the underlying mechanisms and their implications for clinical practice. [ABSTRACT FROM AUTHOR]

Context.--: Autopsies performed on COVID-19 patients have provided critical information about SARS-CoV-2's tropism, mechanisms of tissue injury, and spectrum of disease. Objective.--: To provide an updated database of postmortem disease in COVID-19 patients, assess relationships among clinical and pathologic variables, evaluate the accuracy of death certification, and correlate disease variables to causes of death. Design.--: The 272 postmortem examinations reported in this paper were submitted by 14 pathologists from 9 medical or forensic institutions across the United States. The study spans the eras of the 3 principal COVID-19 strains and incorporates surveyed demographic, clinical, and postmortem data from decedents infected with SARS-CoV-2, including primary and contributing causes of death. It is the largest database of its kind to date. Results.--: Demographics of the decedents reported here correspond well to national statistics. Primary causes of death as determined by autopsy and official death certificates were significantly correlated. When specifically cited disease conditions found at autopsy were correlated with COVID-19 versus non-COVID-19 deaths, only lung findings characteristic of SARS-CoV-2 infection or the absence of lung findings were significantly associated. Conclusions.--: Changes in hospitalization and disease likely stem from longer lifespans after COVID-19 diagnosis and alteration in treatment approaches. Although Omicron variants preferentially replicate in the upper airways, autopsied patients who died of COVID-19 in that time period showed the same lung damage as earlier decedents. Most importantly, findings suggest that there are still unelucidated risk factors for death from COVID-19 including possibly genetic susceptibility. [ABSTRACT FROM AUTHOR]