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Background: Interleukin-18 (IL-18) is involved in endothelial activation and dysfunction, and in the pathogenesis and severity of acute graft-versus-host disease (aGVHD). Its relevance for patient outcome after allogeneic stem cell transplantation (alloSCT) has not yet been comprehensively addressed. Methods: Pre-transplant serum levels of free IL-18 were retrospectively assessed in a cohort of 589 patients (training cohort). Results were validated in 688 patients allografted in a different centre. The primary endpoint was overall survival (OS). Secondary endpoints included incidences of non-relapse mortality (NRM), relapse, and aGVHD. Findings: In the training cohort, higher pre-transplant levels of free IL-18 were significantly associated with worse OS (hazard ratio [HR] per 1-log2 increase, 1.25, P = 0.008) in multivariable models. This was due to a higher hazard of NRM (HR per 1-log2 increase, 1.39, P = 0.001), rather than relapse. The associations of pre-transplant free IL-18 with higher NRM (HR per 1-log2 increase, 1.24, P = 0.02) and shorter OS (HR per 1-log2 increase, 1.22, P = 0.006) were confirmed in the validation cohort. In both cohorts, the correlations of higher pre-transplant free IL-18 serum levels with increased NRM and worse OS were mainly driven by fatal infectious complications. No associations with incidence of aGVHD were observed. Interpretation: Higher pre-transplant levels of free IL-18 were associated with non-relapse and overall mortality after alloSCT. Our results may provide a rationale for prospective studies evaluating IL-18 status and inhibition of IL-18 activity in patients undergoing allografting. Keywords: Interleukin-18, Allogeneic stem cell transplantation, Outcome, Mortality

Background There is limited literature on kidney disease in the Pacific Region, despite it being recognised as a leading cause of death in some Pacific Island nations. Kidney replacement therapy is only available in a handful of Pacific Islands. This paper reports the epidemiology of haemodialysis patients in Samoa. Methods Registry data from the National Kidney Foundation of Samoa was analysed to estimate the incidence and prevalence rates of kidney failure from the rates of haemodialysis in Samoa and to explore some of the demographic features related to kidney failure in Samoa Findings In total, 393 patients have received long-term haemodialysis in the National Kidney Foundation of Samoa since its inception in 2005 until August 2019. 43% of the haemodialysis population were women and the mean age of people dialysed was 54.9 years. The crude mean incidence rate of kidney failure in Samoa, based on treated kidney failure cases, is 224 patients per million population with a crude prevalence of 629 patients per million population. Diabetic nephropathy (69.4%) was the leading cause of kidney failure. Interpretation This is the first paper to report the epidemiology of haemodialysis patients in Samoa and reveals an urgent need for further studies on the extent of chronic kidney disease, and kidney failure, in Samoa to develop country specific prevention strategies to mitigate this growing burden and optimise care for kidney failure patients in Samoa. Funding : No funding was received for this study.

Background: Accurate interpretation of rare genetic variants is a challenge for clinical translation. Updates in recommendations for rare variant classification require the reanalysis and reclassification. We aim to perform an exhaustive re-analysis of rare variants associated with inherited arrhythmogenic syndromes, which were classified ten years ago, to determine whether their classification aligns with current standards and research findings. Methods: In 2010, the rare variants identified throughout genetic analysis were classified following recommendations available at that time. Nowadays, the same variants have been reclassified following current American College of Medical Genetics and Genomics recommendations. Findings: Our cohort included 104 cases diagnosed with inherited arrhythmogenic syndromes and 17 post-mortem cases in which inherited arrhythmogenic syndromes was cause of death. 71.87% of variants change their classification. While 65.62% of variants were classified as likely pathogenic in 2010, after reanalysis, only 17.96% remain as likely pathogenic. In 2010, 18.75% of variants were classified as uncertain role but nowadays 60.15% of variants are classified of unknown significance. Interpretation: Reclassification occurred in more than 70% of rare variants associated with inherited arrhythmogenic syndromes. Our results support the periodical reclassification and personalized clinical translation of rare variants to improve diagnosis and adjust treatment. Funding Statement:This work was supported by Obra Social "La Caixa Foundation" (ID 100010434), Fondo Investigacion Sanitaria (FIS PI16/01203 and FIS, PI17/01690) from Instituto Salud Carlos III (ISCIII), Sociedad Espanola de Cardiologia (Proyecto Investigacion Basica Cardiologia 2015 de los Socios Estrategicos SEC), and “Fundacio Privada Daniel Bravo Andreu”. Declaration of Interests: The authors have no conflicts of interest to declare. Ethics Approval Statement: Genetic analysis was approved by the ethics committee of Hospital Josep Trueta (Girona, Spain) following the Helsinki II declaration. Written informed consent was obtained from all patients included in the study.

Background Tuberculosis (TB) is the leading infectious cause of death worldwide. A major barrier to control of the pandemic is a lack of clinical biomarkers with the ability to distinguish active TB from healthy and sick controls and potential for development into point-of-care diagnostics. Methods We conducted a prospective case control study to identify candidate urine-based diagnostic biomarkers of active pulmonary TB (discovery cohort) and obtained a separate blinded “validation” cohort of confirmed cases of active pulmonary TB and controls with non-tuberculous pulmonary disease for validation. Clean-catch urine samples were collected and analyzed using high performance liquid chromatography-coupled time-of-flight mass spectrometry. Results We discovered ten molecules from the discovery cohort with receiver-operator characteristic (ROC) area-under-the-curve (AUC) values >85%. These 10 molecules also significantly decreased after 60 days of treatment in a subset of 20 participants followed over time. Of these, a specific combination of diacetylspermine, neopterin, sialic acid, and N-acetylhexosamine exhibited ROC AUCs >80% in a blinded validation cohort of participants with active TB and non-tuberculous pulmonary disease. Conclusion Urinary levels of diacetylspermine, neopterin, sialic acid, and N-acetylhexosamine distinguished patients with tuberculosis from healthy controls and patients with non-tuberculous pulmonary diseases, providing a potential noninvasive biosignature of active TB. Funding This study was funded by Weill Cornell Medicine, the National Institute of Allergy and Infectious Diseases, the Clinical and Translational Science Center at Weill Cornell, the NIH Fogarty International Center grants, and the NIH Tuberculosis Research Unit (Tri-I TBRU)., Highlights • Urinary levels of small metabolites appear capable of distinguishing cases of active pulmonary tuberculosis from sick and healthy controls. • Levels of these biomarkers decrease after 60 days of treatment in a longitudinal cohort of 20 participants. • - Many of the identified biomarkers are known inflammatory intermediates that may reflect a specific immune response to tuberculosis. Urine tests are commonly used to enable non-invasive, rapid and point-of-care diagnosis of various infectious diseases. We identified diacetylspermine, neopterin, sialic acid and N-acetylhexosamine as potential urine-based biomarkers for tuberculosis from two independent patient cohorts. These metabolites are known inflammatory intermediates and appear to decrease with anti-tuberculosis therapy in a subset of participants followed over 2 months. If validated, these metabolites have potential to both improve our understanding of the immune reaction to active tuberculosis and facilitate the development of a much-needed clinical biomarker for tuberculosis.

Introduction This study aimed to assess the case completeness of out-of-hospital cardiac arrests (OHCA) in the Norwegian Cardiac Arrest Registry (NorCAR) and describe the differences between the registered and missing patients identified from the case-control assessment. Methods We identified the relevant patients in the Norwegian Patient Registry and the Norwegian Cause of Death Registry and compared them with the patients in NorCAR. Data processors used patient records to confirm if the potential cardiac arrest cases met the inclusion criteria in NorCAR. Results Between 2015 and 2017, 8612 OHCA patients were registered in NorCAR. Through the Patient Registry and the Cause of Death Registry we identified 11,114 potential OHCA patients, 3469 of these were already registered in NorCAR. After evaluating the patient records for the remaining 7645 patients, we found 344 patients (4%), were eligible for inclusion in NorCAR, giving a case completeness of 96%. The registered and missing patients were similar in age and gender distribution. Initial shockable rhythm and presumed cause were also comparable. However, the missing patients more frequently achieved return of spontaneous circulation, were more often transported to hospital, and had higher survival rates. The already registered patients had more key variables registered than the missing patients. Conclusion Our results indicate high case completeness in NorCAR. The missing patients were too few to introduce significant changes in the distribution of patient characteristics, indicating that NorCAR is representative of the Norwegian OHCA population.

Triggering factors of Acute Chest Syndrome (ACS) is a leading cause of death in patients with Sickle Cell Disease (SCD) and targeted therapies are limited. Chlorine (Cl2) inhalation happens frequently, but its role as a potential trigger of ACS has not been determined. In this study, we hypothesized that Cl2 exposure resembling that in the vicinity of industrial accidents induces acute hemolysis with acute lung injury, reminiscent of ACS in humanized SCD mice. When exposed to Cl2 (500 ppm for 30 min), 64% of SCD mice succumbed within 6 h while none of the control mice expressing normal human hemoglobin died (p, Graphical abstract Image 1, Highlights • Chlorine inhalation induces exaggerated hemolysis in sickle mice. • Free heme results in fatal acute chest syndrome in sickle versus control mice. • Chlorinated lipids mediate the effects of chlorine on the red blood cells. • Hemopexin alleviates chlorine induced hypoxia, and acute lung injury. • Therefore, postexposure hemopexin injection improves the survival of sickle mice.

Background: Cancer survivors are at greater risk for cardiovascular disease (CVD) than second malignancy, resulting in a decreased quality of life and increased cost of care. Additional knowledge of CVD prevention by identifying possible risk factors has clinical relevance. Our main objective was to determine the relevance of a clinical index of arterial stiffness, pulse pressure, in predicting CVD mortality in cancer patients, with a second objective to examine its relationship with cancer mortality. Methods: We retrospectively analyzed 781 cancer patients from Third National Health and Nutrition Examination Survey and Linked Mortality File, including demographic, anthropometric, blood pressure, and cause of death. Kaplan-Meier survival curve and Cox hazard regression analyses were performed to assess the relationship between pulse pressure and cardiovascular, cancer, and all-cause mortality. Results: During a mean follow-up time of 8.1 years, 603 deaths, 257 cancer and 151 CVD, occurred. In unadjusted models, the risk of CVD, cancer, and all-cause mortality were 3.8-fold, 5.3-fold, and 1.6-fold higher, respectively, for pulse pressure ≥70 ​mmHg compared to

Background Cause of death data are essential for rational health planning yet are not routinely available in Papua New Guinea (PNG) and Solomon Islands. Indirect estimation of cause of death patterns suggests these populations are epidemiologically similar, but such assessments are not based on direct evidence. Methods Verbal autopsy (VA) interviews were conducted at three sites in PNG and nationwide in Solomon Islands. Training courses were also facilitated to improve data from medical certificates of cause of death (MCCODs) in both countries. Data were categorised into broad groups of endemic and emerging conditions to aid assessment of the epidemiological transition. Findings Between 2017 and 2020, VAs were collected for 1,814 adult deaths in PNG and 819 adult deaths in Solomon Islands. MCCODs were analysed for 662 deaths in PNG and 1,408 deaths in Solomon Islands. The VA data suggest lower NCD mortality (48.8% versus 70.3%); higher infectious mortality (27.0% versus 18.3%) and higher injury mortality (24.5% versus 11.4%) in PNG compared to Solomon Islands. Higher infectious mortality in PNG was evident for both endemic and emerging infections. Higher NCD mortality in Solomon Islands reflected much higher emerging NCDs (43.6% vs 21.4% in PNG). A similar pattern was evident from the MCCOD data. Interpretation The cause of death patterns suggested by VA and MCCOD indicate that PNG is earlier in its epidemiological transition than Solomon Islands, with relatively higher infectious mortality and lower NCD mortality. Injury mortality was also particularly high in PNG. This study was funded by Bloomberg Philanthropies.

Aims: Over the last four decades, in-hospital mortality from acute coronary syndromes (ACS) has declined. We characterized the patients who died in our cardiovascular intensive care unit (CICU) over a 15-year period. Based on these data, we described the changing patient population in the CICU. Methods: This retrospective study compared characteristics of patients who died in our CICU in 2005–6, 2013–4 and 2019. During these 5 years, 13,931 patients were hospitalized; 251 (1.8%) died. The mean age of the patients who died was 76 years, 144 (57%) were men. ACS was the leading cause of admission (93 patients, 37%), and 145 (58%) patients had a history of heart failure prior to hospitalization. The leading cause of death was cardiogenic shock in 104 (41%) patients, septic shock in 48 (19%) patients, and combined cardiogenic and septic shock in 31 (12%). Patients hospitalized in the later years of the study were significantly older (67.7, 69.0 and 70.5 years, 2005–6, 2013–4 and 2019, respectively, p

Background Cardiovascular disease is the leading cause of death in China. The aim of this study was to evaluate the levels of cardiovascular health among Chinese adults and to understand the geographic pattern of cardiovascular health. Methods In 2015, a total of 74,726 respondents aged ≥ 20 years with no history of cardiovascular disease were randomly sampled from 298 counties/districts of 31 provinces in mainland China and were interviewed. Seven metrics, including smoking, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting glucose, were determined. Ideal cardiovascular health was defined as the simultaneous presence of all metrics at the ideal level. A score ranging from 0 to 14 was calculated as the sum of all seven metrics for each province. Scores for cardiovascular health behaviors (smoking, body mass index, physical activity and diet) and those for cardiovascular health factors (smoking, total cholesterol, blood pressure, and fasting glucose) were also calculated. Findings The mean age was 44.4 ± 15.9 years, and 49.3% were women. The age-sex-standardized prevalence of ideal cardiovascular health was universally poor, ranging from 0.02% [95% confidence interval (CI): 0%, 0.05%] in Tibet to 2.76% (95% CI: 0.45%, 5.07%) in Heilongjiang. Ideal diet (7.1%) was the least common factor of the seven metrics in each province and varied considerably across provinces. Other component metrics of ideal cardiovascular health were also spatially patterned. In all provinces, women had higher scores than men for cardiovascular health, health behaviors and health factors. Differences in cardiovascular health and health behavior scores between urban and rural areas were associated with levels of socio-economic development. Interpretation Strategies for addressing poor cardiovascular health require geographic targeting and localized consideration. Funding This research was supported by National Key R&D Program, the Shenzhen Strategic Emerging Industry Development Special Fund, and the Fund of "Sanming" Project of Medicine in Shenzhen.

Background: Coronary artery disease (CAD) is a leading cause of death worldwide and increasing cost for society. Genome wide association studies (GWAS) have identified common variants associated with CAD. Combining single nucleotide polymorphisms (SNPs) into a genetic risk score (GRS) can estimate an individual's genetic burden. Objectives: To investigate whether GRS for CAD can predict hospitalization and mortality. Methods: 23,594 individuals without CAD at baseline and with full data for all covariates from the population based prospective study Malmö diet and cancer study were investigated. The association between hospitalizations was calculated by negative binomial regression and risk of mortality was calculated by Cox proportional hazards regression. The GRS was constructed from 50 SNPs. Results: The study population was divided into quintiles according to the value of GRS. During the mean follow-up time of 17.8 years, 17,254 individuals were hospitalized at least once. Individuals in the highest quintile of GRS were hospitalized 10% more often than individuals in the lowest quintile (IRR: 1.10 [95% CI 1.04–1.16], p = 0.001), mainly for cardiovascular reasons (IRR: 1.31 [95% CI 1.20–1.43], p = 5.17 × 10−10). These individuals had highly increased risk of CVD mortality (HR: 1.44 [1.25–1.66], p = 6.56 × 10−7) but not the risk of mortality due to other causes. Conclusion: Our results suggest that genetic predisposition for CAD can predict hospitalization burden and mortality, especially due to cardiovascular causes, independently of traditional risk factors. As the risk conferred by the GRS is partially modifiable, our results may help to reduce societal costs, individual suffering and prolong life. Keywords: Genetic risk score (GRS), Coronary artery disease (CAD), Hospitalization, Mortality

Background . To define the long-term results of 331 standard Hancock porcine bioprostheses implanted in the mitral position between 1973 and 1980. Methods . Of 331 patients (225 male patients, 68%), mean age 49 ± 10 years (range 14 to 69 years), 88% were in New York Heart Association functional class III or IV and 77% were in atrial fibrillation. Follow-up time extended more than 20 years (mean 13.9 years, range 0.3 to 24.7 years) for a total of 4,601 patient-years. Results . Overall operative mortality was 6.3%. At 5, 10, 15, and 20 years, the actuarial survival rate of patients were 71% ± 2%, 46% ± 3%, 30% ± 3%, and 22% ± 2%, respectively. Actuarial estimates of freedom from structural valve deterioration were 95% ± 1%, 67% ± 3%, 32% ± 3%, and 14% ± 3%; from reoperation were 96% ± 1%, 72% ± 3%, 36% ± 4%, and 18% ± 4%; from thromboembolism were 89% ± 2%, 82% ± 3%, 74% ± 4%, and 51% ± 2%; and from anticoagulant-related hemorrhage were 98% ± 1%, 96% ± 1%, 91% ± 1%, and 86% ± 4%. Estimates of freedom from all valve-related mortality at 5, 10, 15, and 20 years were 89% ± 2%, 76% ± 3%, 64% ± 4%, and 48% ± 4%. Multivariate analysis showed younger age to be a significant risk factor for reoperation. Age at operation did not correlate with structural valve deterioration. Conclusions . The long-term results with the standard Hancock bioprosthesis implanted in the mitral position appear satisfactory, particularly up to 15 years from implantation. Protection from stroke, anticoagulant hemorrhage, and endocarditis was good.

Infection is a leading cause of death worldwide in babies under one month of age who are more susceptible to sepsis due to immature host defence mechanisms. Usually, babies may become acutely unwell from infective pathogens due to specific differences in their respiratory and immune systems. However, with the Covid-19 virus, the focus of this paper, it appears that the neonatal population is not significantly affected in the same way as adults. That said, knowledge about this novel virus is rapidly emerging. Therefore, it is vital that neonatal nurses, midwives and other healthcare professionals are adequately informed and educated about the potential impact on neonatal practice. This review paper draws upon key findings and themes from a selection of recent literature to provide an overview of current knowledge on Covid-19 and the implications for care within the neonatal field. The discussion focuses on the nature of Covid-19, its pathophysiology and transmission relevant to maternal and neonatal care. This is followed by implications for practice; namely, maternal issues, the importance of human breast milk, neonatal care relating to parenting and specific management before a final review of the current World Health Organization guidance.

Summary Background Between 1990 and 2015, the global injury mortality declined, but in countries where the poorest billion live, injuries are becoming an increasingly prevalent cause of death. The vulnerability of this population requires immediate attention from policy makers to implement effective interventions that lessen the burden of injuries in these countries. Our aim was two-fold; first, to review all the evidence on effective interventions for the five main types of unintentional injury; and second, to estimate the potential number of lives saved by effective injury interventions among the poorest billion. Methods For our systematic review we used references in the Disability Control Priorities third edition, and searched PubMed and the Cochrane database for papers published until Sept 10, 2016, using a comprehensive search strategy to find interventions for the five major causes of unintentional injuries: road traffic crashes, falls, drowning, burns, and poisoning. Studies were included if they presented evidence with significant effects sizes for any outcome; no inclusions or exclusions made on the basis of where the study was carried out (ie, low-income, middle-income, or high-income country). Then we used data from the Global Burden of Disease 2015 study and a Monte Carlo simulation technique to estimate the potential annual attributable number of lives saved among the poorest billion by these evidence-based injury interventions. We estimated results for 84 countries where the poorest billion live. Findings From the 513 papers identified, 47 were eligible for inclusion. We identified 11 interventions that had an effect on injury mortality. For road traffic deaths, the most successful interventions in preventing deaths are speed enforcement (>80 000 lives saved per year) and drink-driving enforcement (>60 000 lives saved per year). Interventions potentially most effective in preventing deaths from drowning are formal swimming lessons for children younger than 14 years (>25 000 lives saved per year) and the use of creches to supervise younger children (younger than 5 years; >10 000 lives saved per year). We did not find sufficient evidence on interventions for other causes of unintentional injuries (poisoning, burns, and falls) to run similar simulations. Interpretation Based on the little available evidence, key interventions have been identified to prevent lives lost from unintentional injuries among the poorest billion. This Article provides guidance to national authorities on evidence-based priority interventions that can reduce the burden of injuries among the most vulnerable members of the population. We also identify an important gap in knowledge on the effectiveness and the mortality impacts of injury interventions. Funding Partly supported by the Fogarty International Center of the US National Institutes of Health (Chronic Consequences of Trauma, Injuries, Disability Across the Lifespan: Uganda; #D43TW009284).

Dinitrogen (N2) has been increasingly connected to suicidal deaths. The analysis of N2 in post-mortem cases still represents a major challenge in forensic toxicology and circumstantial data has so far played a major role for the determination of the cause of death. In this paper, after presenting a review of cases of N2 intoxication described in forensic literature, we report the application of two approaches in order to quantify an excess of N2 in post-mortem whole blood collected from a case of suicide by nitrogen inhalation. N2 analyses were performed by GC–MS on the suicidal case and on controls taken from 10 autopsy cases with similar PMI (5 traumatic deaths and 5 deaths by asphyxia). The percentage of N2 was estimated by building a five-point N2 peak area calibration curve (0, 15.6 %, 62.4 % 78.1 %, 100 %) and through an external QC, assessing linearity, accuracy and precision, LLOQ, specificity and stability of N2 in the sample vial. Percentage of N2 of the case was significantly higher than the post-mortem controls (p < 0.05). The N2/O2 ratio of the case and controls was also calculated as an additional indicator, and was significantly higher in the case (p < 0.05). The strengths and the limitation of both methods are reported in the paper. Toxicological confirmation for N2 are rarely performed when the cause of death is evident, probably due to the lack of validated methods and the complexity of the interpretation of N2 concentration in biological fluids. The presented methods can be rapidly and profitably applied with instrumentation normally available in forensic laboratories.

The association between egg consumption and mortality is extremely debatable. This study aimed to investigate the potential dose-response association of egg consumption with risk of mortality from all causes and cause-specific in the general population. The primary comprehensive literature search was conducted in PubMed/Medline, Scopus, ISI Web of Science, and Embase up to March 2021, as well as reference lists of relevant original papers and key journals. We calculated summary RRs and their 95% CIs for the highest and lowest categories, as well as the linear trend estimation of egg intake, using the random-effects model. Thirty-three (32 publications) cohort studies were included. These studies enrolled 2,216,720 participants and recorded 232,408 deaths from all causes. Comparing highest versus lowest egg intake categories was not associated with the risk of mortality from all causes (RR: 1.02; 95% CI: 0.94, 1.11; n = 25), cardiovascular disease (CVD) (RR: 1.04; 95% CI: 0.87, 1.23, n = 11), coronary heart disease (CHD) (RR: 0.98; 95% CI: 0.84, 1.16; n = 10), stroke (RR: 0.81; 95% CI: 0.64, 1.02; n = 9), and respiratory disease (RR: 0.96; 95% CI: 0.53, 1.71; n = 3); however, it was associated with a higher risk of cancer mortality (RR: 1.20; 95% CI: 1.04, 1.39; n = 13). In the linear dose-response analysis, an additional intake of 1 egg per week was associated with a 2% and 4% increased risk of all-cause and cancer mortality, respectively, and a 4% decreased risk of stroke mortality. The certainty of the evidence was rated as low to moderate. Higher egg consumption was not associated with an increased risk of mortality from all causes, CVD, CHD, stroke, or respiratory disease, whereas an elevated risk was observed for cancer mortality. These findings suggest that eggs be consumed in low to moderate amounts (≤1 egg/d) as part of a healthy diet.

Background Colorectal cancer (CRC) is the second major cause of death from cancer in Europe and in the USA. Dietary factors and colonic microflora seem to play an important role in colorectal carcinogenesis, making the potential protective role of probiotics of overwhelming interest. Methods and Aim This article analyzes existing data from basic science (animal and in vitro models) and human (epidemiological and interventional) studies to highlight areas for which more evidence is necessary. We interrogated Medline for studies analysing the risk of CRC and the use of probiotics and also screened the references of identified papers. Results As far as regards animal models, we identified 29 studies aimed at evaluating the effect of probiotics administration on the incidence of CRC and/or of precursor lesions. All but one study using an animal model with spontaneous tumour growth in the background of colitis employed carcinogens, and most studies employed Lactobacilli or Bifidobacteria. All but 3 studies had positive results, and when prebiotics were evaluated too, the combination led to an important synergistic effect. The protective effect of probiotics seemed more important when they were administered before, and not after the carcinogen, and the putative mechanisms are not fully elucidated. Five papers evaluated the effect of probiotics on CRC cell lines in vitro , with results suggesting the ability of probiotics to modulate important cell functions and in a complex interplay. There are few human epidemiological studies specifically designed to analyze the effect of probiotics on CRC incidence, with important confounding factors, such as role of fibers, other dairy products and vitamin D often present. Overall, these studies fail to detect significant effects of fermented milks against CRC. Interventional studies suggest reduction of surrogate markers for CRC risk. However, one recent study showed no significant difference in the development of new CRC following administration of either fibers or probiotics in patients previously treated for colon neoplasm. A single randomised, double blind, placebo controlled pilot interventional trial aimed to evaluate the reduction in cancer risk biomarkers obtainable with the consumption of a symbiotic has been designed and started but a complete final report is not yet available. Conclusions In our search of the literature few and conflicting epidemiologic data regarding the impact of fermented dairy products consumption in humans have been gathered. There are no positive data from interventional studies so far. Therefore, even though an ample body of evidence supports the potential anticarcinogenic action of probiotics on the basis of the results obtained in both in vitro and in vivo models, further evidence is very much needed.

This paper critically reviews an experience of health cooperation in an hospital of a rural area of Ivory Coast. This particular situation is analysed in the more general frame of health problems in low-income countries and may suggest priorities for international health cooperation. The analysis of the main causes of avoidable death in poor countries does indicate targets and tools of intervention. In this case, the target was the reduction of infant mortality from anaemia of different origin and from HIV-1 mother-to-infant transmission. The major tool for intervention was the partnership between an Italian teaching and research hospital and the African hospital, with the catalyst of a non-governmental organisation. This paper analyses the different levels at which cooperation developed in this project, from sheer economic support to the implementation of disease-oriented twinning programs that can improve health care and strengthen research capacity on both sides. Besides, medical, ethical and social implications of the ongoing cooperation program are discussed, with particular reference to the problems of preventing mortality from severe anaemia (diet fortification in children and pregnancy and transfusional guidelines in severe malaria) and of preventing mother-to-child neonatal transmission of HIV-1 infection (counselling and testing pregnant women for HIV-1, nevirapine administering to the mother and the baby and breast-feeding).

The seminal paper by Daniel Bernoulli published in 1766 is put into a new perspective. After a short account of smallpox inoculation and of Bernoulli’s life, the motivation for that paper and its impact are described. It determines the age-specific equilibrium prevalence of immune individuals in an endemic potentially lethal infectious disease. The gain in life expectancy after elimination of this cause of death can be explicitly expressed in terms of the case fatality and the endemic prevalence of susceptibles. D’Alembert developed in 1761 an alternative method for dealing with competing risks of death, which is also applicable to non-infectious diseases. Bernoulli’s formula for the endemic prevalence of susceptibles has so far escaped attention. It involves the lifetime risk of the infection, the force of infection and the life expectancy at birth. A new formula for the basic reproduction number is derived which involves the average force of infection, the average case fatality and the life expectancy at the time of infection. One can use this estimate to assess the gain in life expectancy if only a fraction of the population is immunized.

This paper presents an analysis of the relationships between the passage of key alcohol safety laws and the number of drinking drivers in fatal crashes. The study evaluated three major alcohol safety laws--administrative license revocation laws, 0.10 illegal per se, and 0.08 illegal per se laws--on the proportion of drinking drivers in fatal crashes. Drivers aged 21 and older in fatal crashes at two BAC levels--0.01-0.09 and 0.10 or greater--were considered separately. Drivers under age 21 were not included because they are affected by the Minimum Legal Drinking Age (MLDA) law. This study used data on drinking drivers in fatal crashes from the Fatality Analysis Reporting System (FARS) covering 16 years (1982-1997) for all 50 states and the District of Columbia. Also included in the study were such variables as per capita alcohol consumption and annual vehicle miles traveled (VMT), which could affect the number of alcohol-related crashes. The results indicate that each of the three laws had a significant relationship to the downward trend in alcohol-related fatal crashes in the United States over that period. This paper points out that this long-term trend is not the product of a single law. Instead, it is the result of the growing impact of several laws over time plus the affect of some factors not included in the model tested (such as the increasing use of sobriety checkpoints and the media's attention to the drinking-and-driving problem).

Women and children bear substantial morbidity and mortality as a result of armed conflicts. This Series paper focuses on the direct (due to violence) and indirect health effects of armed conflict on women and children (including adolescents) worldwide. We estimate that nearly 36 million children and 16 million women were displaced in 2017, on the basis of international databases of refugees and internally displaced populations. From geospatial analyses we estimate that the number of non-displaced women and children living dangerously close to armed conflict (within 50 km) increased from 185 million women and 250 million children in 2000, to 265 million women and 368 million children in 2017. Women’s and children’s mortality risk from non-violent causes increases substantially in response to nearby conflict, with more intense and more chronic conflicts leading to greater mortality increases. More than 10 million deaths in children younger than 5 years can be attributed to conflict between 1995 and 2015 globally. Women of reproductive ages living near high intensity conflicts have three times higher mortality than do women in peaceful settings. Current research provides fragmentary evidence about how armed conflict indirectly affects the survival chances of women and children through malnutrition, physical injuries, infectious diseases, poor mental health, and poor sexual and reproductive health, but major systematic evidence is sparse, hampering the design and implementation of essential interventions for mitigating the harms of armed conflicts.

Background Myocardial infarction with non-obstructive coronary arteries (MINOCA) is common and occurs in 6–8% of all patients fulfilling the diagnostic criteria for acute myocardial infarction (AMI). This paper describes the rationale behind the trial ‘Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment (ACEI/ARB) of MINOCA patients’ (MINOCA-BAT) and the need to improve the secondary preventive treatment of MINOCA patients. Methods MINOCA-BAT is a registry-based, randomized, parallel, open-label, multicenter trial with 2:2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce the composite endpoint of death of any cause, readmission because of AMI, ischemic stroke or heart failure in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 3500 patients will be randomized into four groups; e.g. ACEI/ARB and beta blocker, beta blocker only, ACEI/ARB only and neither ACEI/ARB nor beta blocker, and followed for a mean of 4 years. Summary While patients with MINOCA have an increased risk of serious cardiovascular events and death, whether conventional secondary preventive therapies are beneficial has not been assessed in randomized trials. There is a limited basis for guideline recommendations in MINOCA. Furthermore, studies of routine clinical practice suggest that use of secondary prevention therapies in MINOCA varies considerably. Thus results from this trial may influence future treatment strategies and guidelines specific to MINOCA patients.

Infections are a frequent complication and a major cause of death among patients with cirrhosis. The important impact of infections in general and especially spontaneous bacterial peritonitis on the course of disease and prognosis of patients with cirrhosis has been recognized for many years. Nevertheless, such importance has recently increased due to the comprehension of infection as one of the most prominent risk factors for patients to develop acute-on-chronic liver failure. Furthermore, the issue of infections in cirrhosis is a focus of increasing attention because of the spreading of multidrug resistant bacteria, which is an emerging concern among physicians assisting patients with cirrhosis. In the present paper, we will review the current epidemiology of infections in patients with cirrhosis and particularly that of infections caused by resistant bacteria, demonstrating the relevance of the subject. Besides, we will discuss the current recommendations on diagnosis and treatment of different kinds of infections, including spontaneous bacterial peritonitis, and we will highlight the importance of knowing local microbiological profiles and choosing empirical antibiotic therapy wisely. Finally, we will debate the existing evidences regarding the role of volume expansion with albumin in patients with cirrhosis and extraperitoneal infections, and that of antibiotic prophylaxis of spontaneous bacterial peritonitis.

Cancer is the leading cause of death in Singapore since the early 1980s and has remained so since then, accounting for 29.7% of deaths in 2015. Rapid technological advancements in the treatment of cancer and the development of the specialty of radiation and medical oncology demanded nurses with the knowledge and skills to provide care and support to cancer patients and their families. The evolvement of oncology nursing as a specialty in Singapore mirrors many countries due to the increase in cancer incidences as well as the development of medical specialty in the treatment of cancer. This paper traces the development of oncology nursing as a clinical specialty in Singapore. The historical perspective maps up the factors that caused oncology nursing to develop as a specialty within nursing practice. As cancer continues to be the leading cause of mortality for many years to come in Singapore and cancer care continues to evolve, the roles of oncology nurses will continue to unfold and expand as part of an interdisciplinary team in the fight against cancer.

Epidemiological studies on the impact of outdoor temperature to human health have demonstrated the capability of humans to adapt to local climate. However, there is limited information on the association between indoor temperature and human health, despite people spending most of their time indoors. The problem stems from the lack of sufficient indoor temperature measurement in the population. To overcome this obstacle, this paper presents an indirect epidemiological approach to evaluate the impact of high indoor temperature on mortality. The relationships between indoor-outdoor temperatures in different climate zones identified in the literature were combined with the outdoor temperature-mortality curves of the same locations to obtain the local indoor minimum mortality temperatures (iMMT), the temperature at which mortality is lowest, which by implication is the temperature at which the population is most comfortable on average. We show that the iMMT varies and has a weak linear relationship with the distance to the equator, which provides evidence of human adaptation to local indoor temperatures. These findings reinforce the adaptive comfort theory, which states that people can adapt to local indoor environment and establish their thermal comfort. Recognising the human adaptability to local climate will direct flexible and optimized policy to protect public health against extreme temperature events. This will also help reduce energy consumption for regulating indoor temperature without compromising the occupants' health.

HIV/AIDS was the main cause of death among young adults in the 1990s. The sexual freedom from the rise of contraceptives and women's empowerment affected individuals' preferences for dating, marriage and fertility. In this paper, we investigate whether the HIV/AIDS epidemic from the 1980s onward, a non-monetary shock, affected people's preferences for marriage. We set out a simple two period non-cooperative model and demonstrate that under growing likelihood of meeting someone infected by AIDS, the expected payoff of people who got married in the first period increased. Then, using unique Brazilian data, we estimate the marriage gain in two different time spans, 1984 to 1991 and 1999 to 2010, respectively before and after the free distribution of antiretrovirals by the Brazilian government. Our findings corroborate that HIV/AIDS influenced marriages in the past, working as a response against the risk of being infected and increasing the marital surplus, especially for women. We also find evidence that the impact of HIV/AIDS on marriage disappeared once antiretroviral drugs were universally distributed, which significantly reduced the mortality risk of the disease, and therefore the expected costs of the disease. The perceived vulnerability to the consequences of HIV/AIDS decreased, resulting in a change in sexual behavior, thus reducing the value of monogamous relationships compared to the period without antiretroviral drugs (ARVs).

This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in 5 of the 23 patients. Two of the Houston cases had interstitial pneumonia with diffuse alveolar damage pattern. One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in nonhemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia. Multifocal acute injury of cardiac myocytes was frequently observed. Lymphocytic myocarditis was reported in 1 case. In addition to major pulmonary pathology, the 3 Houston cases had evidence of lymphocytic pericarditis, multifocal acute injury of cardiomyocytes without inflammatory cellular infiltrates, depletion of splenic white pulp, focal hepatocellular degeneration and rare glomerular capillary thrombosis. Each had evidence of chronic cardiac disease: hypertensive left ventricular hypertrophy (420 g heart), dilated cardiomyopathy (1070 g heart), and hypertrophic cardiomyopathy (670 g heart). All 3 subjects were obese (BMIs of 33.8, 51.65, and 35.2 Kg/m2). Overall, the autopsy findings support the concept that the pathogenesis of severe COVID-19 disease involves direct viral-induced injury of multiple organs, including heart and lungs, coupled with the consequences of a procoagulant state with coagulopathy.

Suicide by hanging is a sentinel event and a major cause of death in prisons, with an increasing frequency over recent years. The rapid detection of suicidal behavior can reduce the mortality rate and increase the odds of survival for the suicide victim. Significant efforts have been made to develop technologies for preventing hanging attempts, but most of them use cumbersome devices, or they are mainly depending on human attention and intervention. In this paper, we propose a vision-based method to automatically detect suicide by hanging. Our intelligent video surveillance system operates using depth streams provided by an RGB-D camera, regardless of illumination conditions. The proposed algorithm is based on the exploitation of the body joints’positions to model suicidal behavior. Both dynamic and static pose characteristics are calculated in order to efficiently capture the body joints’movement and model suicidal behavior. Results from the experiments on realistic video sequences, show that our system achieves a high accuracy in detecting suicide attempts, while meeting real-time requirements.

Life expectancy has increased in the United States over many decades. The difference in life expectancy between black and white Americans has also decreased, but some states have made much more progress towards racial equality than others. This paper describes the pattern of contributions of six major causes of death to the black-white life expectancy gap within US states and the District of Columbia between 1969 and 2013, and identifies states diverging from the overall pattern. Across multiple causes, the District of Columbia, Illinois, Wisconsin, and Michigan had the highest contributions to black-white inequality, while New York, Massachusetts, and Rhode Island had the lowest contributions and have either achieved or are the closest to achieving black-white equality in life expectancy.

Objective Death certificates are an invaluable source of cancer mortality statistics. However, this value can only be realised if accurate, quantitative data can be extracted from certificates—an aim hampered by both the volume and variable quality of certificates written in natural language. This paper proposes an automatic classification system for identifying all cancer related causes of death from death certificates. Methods Detailed features, including terms, n-grams and SNOMED CT concepts were extracted from a collection of 447,336 death certificates. The features were used as input to two different classification sub-systems: a machine learning sub-system using Support Vector Machines (SVMs) and a rule-based sub-system. A fusion sub-system then combines the results from SVMs and rules into a single final classification. A held-out test set was used to evaluate the effectiveness of the classifiers according to precision, recall and F-measure. Results The system was highly effective at determining the type of cancers for both common cancers (F-measure of 0.85) and rare cancers (F-measure of 0.7). In general, rules performed superior to SVMs; however, the fusion method that combined the two was the most effective. Conclusion The system proposed in this study provides automatic identification and characterisation of cancers from large collections of free-text death certificates. This allows organisations such as Cancer Registries to monitor and report on cancer mortality in a timely and accurate manner. In addition, the methods and findings are generally applicable beyond cancer classification and to other sources of medical text besides death certificates.

Background: Hemodynamic support with Impella (Abiomed Inc., Danvers, MA) devices is becoming a more prevalent treatment option for patients with cardiogenic shock (CS) undergoing percutaneous coronary intervention (PCI). There exists only limited published data regarding outcome differences between male and female patients. Therefore, the objective of this paper is to analyze these gender differences between short-term survival and in-hospital outcomes in those undergoing PCI with CS. Methods: Between January 2011 and July 2016, patients undergoing PCI with simultaneous use of Impella were identified. Only patients presenting with CS were included in the analysis. All-cause in-hospital mortality was the primary outcome. Using SAS 9.4 for propensity score matching, additional secondary outcomes were also compared. Results: The primary outcome was comparable between males and females (39.5% vs. 26.3%, p = 0.33) in CS patients. Secondary outcomes were also comparable and included: myocardial infarction, stroke, CS, heart failure, dialysis requirement, bleeding within 72 h, blood transfusion, dysrhythmia, composite of all complications, major adverse cardiac events. Survival at 30 days was equal in both groups. A reduced mortality in males was noted for pre-PCI initiation of Impella. Additionally, both genders who received pre-PCI Impella support, experienced a significant reduction in inotrope use. Conclusions: Despite the small number of cohorts, this study did not reveal any significant differences among gender with the use of percutaneous left ventricular assist devices for PCI in patients with acute myocardial infarction complicated by CS. However, initiation of Impella prior to PCI may be associated with improved mortality and morbidity in both genders. Keywords: Mechanical circulatory device, Cardiogenic shock, High-risk PCI, Gender

Detainees may be subjected to torture and extra-judicial execution by State actors and terrorists. But, the pathology of torture has not been well-described. This is due to the lack of autopsies performed on victims of torture, mostly due to the disposal of the bodies of the victims by their torturers. On this basis, the cause of death of detainees subjected to torture is often a matter of speculation or remains obscure. This paper provides an overview of the pathology of torture based on the authour's experience with the autopsies of torture victims. At autopsy, many different types of inflicted injuries may be observed, often ranging in severity. However, three recurrent patterns of trauma that are the hallmarks of torture were recognized by the authour: (1) blunt impact trauma characterized by bruises, patterned injuries, and internal injuries; (2) electrical and thermal injuries; and (3) injuries from stress positions that occur from prolonged suspension. The most under-recognized form of fatal torture are the complications of stress positions related to suspension of the victim's body by the upper, or lower extremities. For example, prolonged suspension by reverse hanging (suspension of the victim's body by the wrists or forearms with the arms extended backward at the shoulder joint) can cause over-stretching and necrosis of the muscles of the shoulder, resulting in fatal myoglobinuric renal failure. It is essential that autopsies be performed on all detainees who die in custody, to determine if torture played a role in death. Furthermore, the true nature of the injuries sustained often remains obscure unless a musculocutaneous dissection is performed. Specifically, dissection of the back, limbs and the soles of the feet, as well as the shoulders and knees is essential to determine if specific forms of torture have been applied. This is especially true for fatal complications of stress positions. Seeking the truth about the medical consequences of fatal torture will raise awareness about torture-related injuries, assist in rehabilitation of torture survivors, and strengthen forensic humanitarian action.

Background Synthetic fentanyl analogues are highly potent opioid drugs which have no pharmaceutical use in humans. We detected the synthetic fentanyl analogues; carfentanil, butyryl fentanyl, fluorobutyrylfentanyl, furanylfentanyl, and alfentanil as well as fentanyl itself in 25 cases in early 2017. There have been no previous reports of synthetic fentanyl deaths in the United Kingdom (UK). Methods Cases in which the history clearly stated drug use but where a post mortem blood morphine concentration was lower than would be expected to explain the sudden death, were referred for further analysis by high resolution accurate mass (HRAM) mass spectrometry. Results 25 post mortem cases in which synthetic fentanyl analogues were implicated in the cause of death were reported from January to May 2017. No cases were seen in June 2017. The age range was 21–54 years and 22 were male. There was a history of heroin use, or markers of heroin use on toxicology screening in 21/25 cases. Carfentanil and fentanyl were detected in 7 cases. Multiple synthetic fentanyl analogues were present in 13 cases, with the remaining 5 cases having only carfentanil present. Synthetic fentanyl analogues were detected in combination with other drugs in all cases. Significant concentrations of ethanol were detected in only 2 cases. The concentration range of carfentanil in blood was 90–4004 pg/mL. Of note, the 3 cases in which ante mortem carfentanil was quantified ranged from 21 to 98 pg/mL. In all cases, death was attributed to combined central nervous system depression. Conclusions This paper highlights a new and rapid emergence of these drugs into the UK illicit drug arena. Synthetic fentanyl analogues represent a significant challenge both analytically and clinically within the groups who misuse drugs. It is worthwhile considering the possibility of the presence of these drugs in cases in which a toxicological cause of death is not apparent analytically but there is a history of drug use and circumstantial evidence exists to support a drug-related death as the most likely cause. It may be that synthetic fentanyl analogues should be screened for routinely to avoid reporting any false negative results, but the cost implications and viability of this have not been fully evaluated.

Aims: Studies consistently identify substance treatment populations as more likely to die prematurely compared with age-matched general population, with mortality risk higher out-of-treatment than in-treatment. While opioid-using pharmacotherapy cohorts have been studied extensively, less evidence exists regarding effects of other treatment types, and clients in treatment for other drugs. This paper examines mortality during and following treatment across treatment modalities.\ud \ud Methods: A retrospective seven-year cohort was utilised to examine mortality during and in the two years following treatment among clients from Victoria, Australia, recorded on the Alcohol and Drug Information Service database by linking with National Death Index. 18,686 clients over a 12-month period were included. Crude (CMRs) and standardised mortality rates (SMRs) were analysed in terms of treatment modality, and time in or out of treatment.\ud \ud Results: Higher risk of premature death was associated with residential withdrawal as the last type of treatment engagement, while mortality following counselling was significantly lower than all other treatment types in the year post-treatment. Both CMRs and SMRs were significantly higher in-treatment than post-treatment.\ud \ud Conclusion: Better understanding of factors contributing to elevated mortality risk for clients engaged in, and following treatment, is needed to ensure that treatment systems provide optimal outcomes during and after treatment.

3-methoxyphencyclidine (3-MeO-PCP) appeared on the illicit drug market in 2011 and is an analogue of phencyclidine, which exhibits anesthetic, analgesic and hallucinogenic properties. In this paper, we report data from a non-fatal intoxication and seven deaths involving 3-MeO-PCP in Sweden during the period March 2014 until June 2016.The non-fatal intoxication case, a 19-year-old male with drug problems and a medical history of depression, was found awake but tachycardic, hypertensive, tachypnoeic and catatonic at home. After being hospitalized, his condition worsened as he developed a fever and lactic acidosis concomitant with psychomotor agitation and hallucinations. After 22h of intensive care, the patient had made a complete recovery. During his hospitalization, a total of four blood samples were collected at different time points. The seven autopsy cases, six males and one female, were all in their twenties to thirties with psychiatric problems and/or an ongoing drug abuse.3-MeO-PCP was identified with liquid chromatography (LC)/time-of-flight technology and quantified using LC-tandem mass spectrometry.In the clinical case, the concentration of 3-MeO-PCP was 0.14μg/g at admission, 0.08μg/g 2.5h after admission, 0.06μg/g 5h after admission and 0.04μg/g 17h after admission. The half-life of 3-MeO-PCP was estimated to 11h. In the autopsy cases, femoral blood concentrations ranged from 0.05μg/g to 0.38μg/g. 3-MeO-PCP was the sole finding in the case with the highest concentration and the cause of death was established as intoxication with 3-MeO-PCP. In the remaining six autopsy cases, other medications and drugs of abuse were present as well.Despite being scheduled in January 2015, 3-MeO-PCP continues to be abused in Sweden. Exposure to 3-MeO-PCP may cause severe adverse events and even death, especially if the user does not receive life-supporting treatment.

Objectives The purpose of this study was to perform the first meta-analysis of currently available data. Background Soluble suppression of tumorigenesis 2 (sST2) plasma concentration is elevated in chronic heart failure (CHF) and helps to predict prognosis in this setting, although the evidence is limited. Methods Three databases (Medline, Cochrane Library, and Scopus) were searched. Inclusion criteria were: follow-up studies; papers published in English; enrollment of CHF outpatients; available data on hazard ratio (HR) for the log2 ST2 (so that the reported HRs represent the risk per doubling of sST2) and 95% confidence interval (CI) for all-cause death, and possibly also for cardiovascular (CV) death; and use of standardized sST2 assay. Exclusion criteria were: sST2 considered only as an element of a prognostic score, and studies on patients with end-stage HF. Results Seven studies were finally included for all-cause death, with a global population of 6,372 patients; data on CV death were available for 5 studies, totaling 5,051 patients. The HR was 1.75 (95% CI: 1.37 to 2.22) for all-cause death and 1.79 (95% CI: 1.22 to 2.63) for CV death (both p Conclusions sST2 is a predictor of both all-cause and CV death in CHF outpatients. The present meta-analysis supports the use of sST2 for risk stratification in patients with stable CHF.

Cancer is the third highest cause of death in Kenya, preceded by infectious and cardiovascular diseases, and in most cases, diagnosed in later stages. Nurses are the primary caregivers, assessing and managing these patients in the clinic, in inpatient settings, and in rural and remote communities. While cancer rates remain high, the burden to the patient, the caregiver, and society as a whole continues to rise. Kenya's poverty complicates cancer even further. Many Kenyans are unaware of cancer's signs and symptoms, and limited diagnostic and treatment centers are available. Despite these barriers, there is still hope and help for those in Kenya, who suffer from cancer. The World Health Organization has stated that palliative care is a basic human right and nurses providing this care in Kenya are making efforts to support cancer patients' ongoing needs, in order to promote compassionate palliative care and prevent suffering. The purpose of this paper is to address the palliative care needs of patients with cancer in Kenya by providing education to nurses and influencing health-care policy and education at micro and macro levels. A case study weaved throughout will highlight these issues.

Purpose Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the Saudi Arabia (KSA). Over the last decade dyslipidemia has been the predominant risk factor in KSA. The linear relationship between low density lipoprotein cholesterol (LDL-C) levels, a marker for dyslipidemia, and progression of ASCVD is well established. The objective of this paper is to to provide an overview of the burden of disease, outline current clinical practice guidelines (CPG), examine gaps in care, and provide actionable recommendations to prevent, diagnose, and treat dyslipidemia in KSA. Results Saudi Arabia has the highest prevalence of ASCVD in the Gulf region. Several gaps in the implementation of CPGs, including the underdiagnosis and undertreatment of dyslipidemia, inadequate primary and secondary prevention efforts, complicated by a fragmented health system have been identified. Compelling evidence indicates that target LDL-C levels are not achieved throughout the Middle East region. In addition, high-risk patients are often left unidentified with adequate treatment. Conclusion This statement recommends specific multilevel interventions to optimize the prevention, diagnosis, and treatment of ASCVD. These recommendations focus on strengthening primary and secondary prevention through education initiatives, establishment of specialized prevention and treatment centers, and development of local and regional CPGs.

Purpose This paper compares the mortality burden of heart disease versus cancer among women by age, race, and ethnicity. Methods U.S. death and population data for the years 2000 through 2013 were used to calculate heart disease and cancer death rates. Detailed analyses focused on age (15–19 years old to ≥100 years old) and race and ethnicity (Whites, Blacks, Hispanics, Asians and Pacific Islanders (A/PIs), and American Indians and Alaska Natives (AI/ANs)). Results Among women aged 15 years and older, there were 289,467 heart disease deaths and 276,716 cancer deaths in 2013. The majority of heart disease deaths (51.6%) occurred among women 85 years or older, compared with 18.9% of female cancer deaths. The age-adjusted death rates (per 100,000 population) were 171 (95% confidence interval [CI], 170–171) for heart disease versus 177 (95% CI, 176–178) for cancer. For all racial and ethnic groups, cancer mortality was significantly higher than heart disease mortality among women younger than 80 years of age. For all ages combined, cancer deaths exceeded heart disease deaths among Hispanics, A/PIs, and AI/ANs. Black non-Hispanic women were the only racial/ethnic group who had a higher age-adjusted death rate for heart disease than for cancer: 224 (95% CI, 222–226) versus 207 (95% CI, 205–209). Conclusions Heart disease remains the leading cause of death among all women combined in the United States by a narrow margin. However, cancer predominantly kills middle-aged and young women, whereas heart disease predominantly kills the very old. New research on the overreporting of heart disease on death certificates for elderly women is needed. National summary statistics obscure the fact that cancer is already the overall leading cause of death for Hispanic women, Asian and Pacific Islander women, and American Indian and Alaska Native women.

International audience; Mortality data, by the unambiguity of their definition and understanding by all stakeholders, and completeness of registration, are a cornerstone of public health statistics in France and in most industrialized countries. This article describes the data production process, and the main types of possible analyses. Data production is composed of different stages: death certification by a medical doctor on paper or electronic (using a web application) format, data transmission to Inserm, capture and coding of information. The encoding of the information follows the WHO recommendations of the International Classification of Diseases ([ICD], 10th revision used since 2000). It is carried out using an automatic coding software, called Iris, developed in an international consortium. The coding aims, first, at assigning an ICD code to all nosologic entities encountered on the certificate, and then at selecting the underlying cause of death. The latter is the main information used for statistical analyses. Three main types of analysis emerge in the literature: the exploitation of data on the death certificate only, ecological analyses (studies of associations between variables measured across groups) and analysis from data individually linked to other databases. Many public health issues can be addressed with these various analyses. Several developments in the production process are being implemented: the deployment of electronic certification, increased automation of the death certificate information processing and durable and complete record linkage with health insurance and hospitalisation data. They could soon be deeply expanding the scope of possible uses of causes of death data.

Microbially mediated mechanisms of human decomposition begin immediately after death, and are a driving force for the conversion of a once living organism to a resource of energy and nutrients. Little is known about post-mortem microbiology in cadavers, particularly the community structure of microflora residing within the cadaver and the dynamics of these communities during decomposition. Recent work suggests these bacterial communities undergo taxa turnover and shifts in community composition throughout the post-mortem interval. In this paper we describe how the microbiome of a living host changes and transmigrates within the body after death thus linking the microbiome of a living individual to post-mortem microbiome changes. These differences in the human post-mortem from the ante-mortem microbiome have demonstrated promise as evidence in death investigations. We investigated the post-mortem structure and function dynamics of Staphylococcus aureus and Clostridium perfringens after intranasal inoculation in the animal model Mus musculus L. (mouse) to identify how transmigration of bacterial species can potentially aid in post-mortem interval estimations. S. aureus was tracked using in vivo and in vitro imaging to determine colonization routes associated with different physiological events of host decomposition, while C. perfringens was tracked using culture-based techniques. Samples were collected at discrete time intervals associated with various physiological events and host decomposition beginning at 1 h and ending at 60 days post-mortem. Results suggest that S. aureus reaches its highest concentration at 5–7 days post-mortem then begins to rapidly decrease and is undetectable by culture on day 30. The ability to track these organisms as they move in to once considered sterile space may be useful for sampling during autopsy to aid in determining post-mortem interval range estimations, cause of death, and origins associated with the geographic location of human remains during death investigations.

MDMB-CHMICA is a synthetic cannabinoid that appeared on the European drug market in September 2014. This substance was found in Poland in the herbal mixture "Mocarz" ("Strongman"), which caused a large outbreak of intoxications at the beginning of July 2015. This paper describes the circumstances of death and toxicological findings in a fatal intoxication with MDMB-CHMICA (in combination with alcohol). Loss of consciousness and asystole occurred a few minutes after smoking the 'legal high'. The man died after 4 days of hospitalisation. The cause of death accepted by the medical examiner was multiple organ failure. MDMB-CHMICA was detected and quantified in blood (ante- and postmortem) and internal organs tissues. The samples were analysed using liquid chromatography with mass spectrometry (LC-MS/MS). The concentration of MDMB-CHMICA in antemortem blood was 5.6 ng/mL. Although the death occurred after 4 days from administration a relatively high concentration (2.6 ng/g) was estimated in the brain. Traces of this compound were also found in other postmortem materials (blood, stomach, liver, bile, and kidney). The presented case shows the health risks associated with MDMB-CHMICA use. The administration of this substance can lead to the number of organ failures, cardiac arrest and consequently death.

Although implantable cardioverter-defibrillators (ICDs) are frequently viewed as a lifelong commitment in that patients are routinely scheduled for generator exchange (GE) at end of battery life, several considerations should prompt a reevaluation of risks and benefits before GE. Compared with initial ICD implant, patients receiving replacement devices are older, and have more comorbidities and shorter life expectancy, all of which may limit the benefit of ICD therapy following GE. Additionally, GE is associated with significant complications, including infection, which may increase the risk of mortality. In this paper, we review recent data regarding opportunities for risk stratification before GE, with a particular focus on those with improved left ventricular function and those who have not experienced ICD therapies during the first battery life. We also provide a broader perspective on ICD therapy, focusing on how decisions regarding GE may affect goals of care at the end of life.

Traumatic Brain Injury (TBI) is recognized as an important cause of death and disabilities after an accident. The availability a tool for the early diagnosis of brain dysfunctions could greatly improve the quality of life of people affected by TBI and even prevent deaths. The contribution of the paper is a process including several methods for the automatic processing of electroencephalography (EEG) data, in order to provide a fast and reliable diagnosis of TBI. Integrated in a portable decision support system called EmerEEG, the TBI diagnosis is obtained using discriminant analysis based on quantitative EEG (qEEG) features extracted from data recordings after the automatic removal of artifacts. The proposed algorithm computes the TBI diagnosis on the basis of a model extracted from clinically-labelled EEG records. The system evaluations have confirmed the speed and reliability of the processing algorithms as well as the system's ability to deliver accurate diagnosis. The developed algorithms have achieved 79.1% accuracy in removing artifacts, and 87.85% accuracy in TBI diagnosis. Therefore, the developed system enables a short response time in emergency situations and provides a tool the emergency services could base their decision upon, thus preventing possibly miss-diagnosed injuries.

The role of procalcitonin (PCT) as a biomarker for sepsis in adults is well documented, while its role in infections affecting neonatal children remains controversial. Among these infections, Community-Acquired pneumonia (CAP) has been studied extensively, because it's the second cause of death in children in developing countries, and one of the most frequent causes of hospitalization in industrialized countries. The PubMed database and the Cochrane Library were used to search for the following keywords: CAP, procalcitonin, and children. Thirteen articles were studied to determine the role of PCT in CAP management, specifically its usefulness for distinguishing pneumococcal infections from viral and unknown infections, for predicting severity and the correct antibiotic treatment. This paper focuses on the studies performed to identify the best inflammatory biomarker for CAP management. Although there is an increase in studies confirming the usefulness of PCT in CAP management in children, further studies are needed to have better understanding of its role for pediatric CAP management.

Two recent UK reports have highlighted data of concern in relation to potentially preventable epilepsy deaths. Public Health England, an executive agency of the Government Department of Health, using National Health Service data from 2001 to 2014 reported a rise in direct age-standardised mortality for epilepsy-associated deaths, in contrast to a reduction in all-cause deaths over the same period. Premature death was seen in people aged below 50 years, especially in men, and where epilepsy was a contributory cause rather than an association. The Scottish Epilepsy Deaths Study, analysing deaths between 2009 and 2016, similarly found death in those with epilepsy was significantly higher than the matched population below the age of 54, especially between the ages of 16 and 24 (6 times higher). Sudden unexpected death in epilepsy accounted for 38% of epilepsy-related deaths under the age of 45. Both studies found a strong relationship between risk of death and deprivation; we discuss the implications of these and other data for planning service delivery and improving epilepsy care. This paper is for the Special Issue: Prevent 21: SUDEP Summit - Time to Listen.

The paper provides an overview of a neighbourhood level classification of mortality for England and Wales (2006-2009). Standardised mortality ratios for 63 causes of death were calculated for middle super output areas (weighted by prevalence). A k-means partitional method was used to classify the data. An eight cluster solution was found to best segment mortality patterns. Clusters mostly differentiated in terms of prevalence, however the importance of neurodegenerative diseases and causes related to unhealthy behaviours were important. The results describe a neighbourhood classification that can be an important tool to help inform policy development, resource allocation and targeting of services.

Use and abuse of alcohol are common findings when unnatural deaths are investigated as evidenced by high blood- and urine- alcohol concentrations (BAC and UAC) at autopsy. Because ethanol is metabolized in the liver until the time of death, the autopsy BAC or UAC might be negative even though the deceased had consumed alcohol in the immediate ante-mortem period. Analysis of the non-oxidative metabolite of ethanol [ethyl glucuronide (EtG)] offers a more sensitive test of recent drinking. In this paper, we determined the concentrations of ethanol and EtG in urine samples from 972 consecutive forensic autopsies. In 425 cases (44%) both EtG and ethanol were positive, which supports ante-mortem drinking. In 342 cases (35%), both EtG and ethanol was negative, which speaks against any consumption of alcohol just before death. In 181 cases, ethanol was negative in urine (0.2 g/kg), whereas EtG was positive (0.5 mg/L), which points towards ingestion of alcohol some time before death. In these cases, mean and median concentrations of EtG were 53.2 mg/L and 23.7 mg/L, respectively, although there was no mention of alcohol on 131 of the death certificates. Alcohol was mentioned on death certificates as an underlying or immediate cause of death or a contributing factor in 435 (45%) cases, which rose to 566 (58%) cases when positive EtG results were included. This article demonstrates the usefulness of EtG analysis in routine post-mortem toxicology when ante-mortem drinking and alcohol-related deaths are investigated.

With advances in antiretroviral therapy (ART), individuals with human immunodeficiency virus (HIV) infection are living longer and increasingly die of non–HIV-related diseases, such as cardiovascular disease (CVD). Several observational studies suggest that HIV-infected patients on ART are at increased risk of CVD; however, the precise mechanisms underlying the association between HIV infection and CVD risk are uncertain. Atherosclerosis and arterial disease in HIV-infected individuals is a multifactorial process with several potential targets for research and therapeutic intervention. This paper critically reviews the contributions of imaging to our understanding of arterial disease, atherosclerosis, and CVD risk in HIV-infected individuals. In general, the findings of studies using carotid ultrasound, coronary computed tomographic angiography, and aortic positron emission tomography agree with those from observational studies of CVD events and suggest that HIV infection is associated with an increased risk of CVD. Observational studies of CVD outcomes and studies using carotid intima-media thickness suggest that there is a moderate increase in CVD risk related to HIV serostatus. Less can be said about the role of ART and specific ART therapies in CVD risk, mainly because imaging studies have had serious methodological limitations that diminish their generalizability. Brachial artery reactivity testing has been especially useful for elucidating the arterial pathophysiology of HIV infection and its treatments, as well as the arterial effects of interventions for treating HIV and dyslipidemia. Aortic positron emission tomography has been especially useful for evaluating arterial inflammation. Coronary artery calcium has not proven to be a useful marker of subclinical atherosclerosis in HIV-infected individuals. Imaging studies support the intriguing hypothesis that persistent inflammation and immune dysregulation contribute to increased CVD risk among treated and suppressed patients with HIV infection.

We read with interest the paper by Witt et al,1 which details the visual examination of Chopin's heart. The organ is described as massively enlarged and completely covered with whitish, massive fibrillary coating.1 Tuberculous (TB) pericarditis coupled with massive enlargement of the right ventricle, possibly due to pulmonary hypertension, was proposed as the most plausible cause of death of the artist.1 The retrospective diagnosis of probable TB pericarditis was made by the authors based on the identification of three small nodules, between several mm up to 1 cm in diameter, of white-glass appearance, two on an upper part of the ventricle one just near the apex (Figure, A).1 However, these nodules were not examined histologically.