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Objective: We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection. Background: Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease. Method: In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram. Results: High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables. Conclusions: Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.

Breast cancer and stroke were leading cause of cancer-related mortality in the world. Stroke is the second leading cause of death. Previous studies showed that patients with breast cancer had a relatively higher risk of sleep disorders. Sleep disorders increased the risk of stroke. The aim of our study was to examine the risk of stroke after a breast cancer with sleep disorder among women in Taiwan. The Taiwan Cancer Registry was used to identify patients with breast cancer. Patients with new-onset breast cancer from January 2007 to December 2015 were selected for this study and followed until December 31, 2017. Patients who were diagnosed with sleep disorders were set as the case group, and the controls were those without sleep disorders. We enrolled 5256 patients with sleep disorders and 10,512 patients without sleep disorders. There were 121 (2.30%) patients with ischemic stroke among the breast cancer patients with sleep disorders. The mean time from the diagnosis of breast cancer to the occurrence of ischemic stroke was 6.29±2.59 years for breast cancer patients with sleep disorders and 6.00±2.76 years for those without sleep disorders (p < 0.0001). After matching by age and index year, breast patients with sleep disorders had a 1.31-fold higher risk (95% confidence interval: 1.03-1.66; p-value=0.026) of ischemic stroke than those without sleep disorders, after adjustment for comorbidities, cancer clinical stage, and treatment types. In conclusion, Breast cancer patients with sleep disorders have an increased risk of stroke.

Background Cardiovascular disease is the leading cause of death worldwide. Early recognition, diagnosis, and reperfusion are the key elements of treatment for ST-segment elevation myocardial infarction. The absence of a prehospital 12-lead electrocardiogram (P12ECG) can cause definitive treatment delay and repeated transfer. Although guidelines highly recommend the measurement and transmission of P12ECG data, P12ECG use has not been widely established. Objective The aim of this study was to verify the time-efficiency and feasibility of the use of a patchy-type 12-lead ECG measuring and transmitting device (P-ECG) by an emergency medical technician (EMT) in an ambulance during patient transport. Methods This was a simulation-based prospective randomized crossover-controlled study that included EMTs. The participants were randomly assigned to one of two groups. Group A began the experiment with a conventional 12-lead ECG (C-ECG) device and then switched to the intervention device (P-ECG), whereas group B began the experiment with the P-ECG and then switched to the C-ECG. All simulations were performed inside an ambulance driving at 30 km/h. The time interval was measured from the beginning of ECG application to completion of sending the results. After the simulation, participants were administered the System Usability Scale questionnaire about usability of the P-ECG. Results A total of 18 EMTs were recruited for this study with a median age of 35 years. The overall interval time for the C-ECG was 254 seconds (IQR 247-270), whereas the overall interval time for the P-ECG was 130 seconds (IQR 112-150), with a significant difference (P Conclusions Performance of 12-lead ECG examination and transmission of the results using P-ECG are faster than those of C-ECG during ambulance transport. With the additional time afforded, EMTs can provide more care to patients and transport patients more rapidly, which may help reduce the symptoms-to-balloon time for patients with acute coronary syndrome. Trial Registration ClinicalTrials.gov NCT04114760; https://www.clinicaltrials.gov/ct2/show/NCT04114760

Aims To evaluate the impact of chronic obstructive pulmonary disease (COPD) on 10-year all-cause death and the treatment effect of CABG versus PCI on 10-year all-cause death in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) and COPD. Methods Patients were stratified according to COPD status and compared with regard to clinical outcomes. Ten-year all-cause death was examined according to the presence of COPD and the revascularization strategy. Results COPD status was available for all randomized 1800 patients, of whom, 154 had COPD (8.6%) at the time of randomization. Regardless of the revascularization strategy, patients with COPD had a higher risk of 10-year all-cause death, compared with those without COPD (43.1% vs. 24.9%; hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.56–2.64; p p = 0.858), whereas among those without COPD, CABG had a significantly lower risk of 10-year all-cause death (22.7% vs. 27.1%; HR: 0.81; 95% CI: 0.67–0.99, p = 0.041). There was no significant differential treatment effect of CABG versus PCI on 10-year all-cause death between patients with and without COPD (pinteraction = 0.544). Conclusions COPD was associated with a higher risk of 10-year all-cause death after revascularization for complex coronary artery disease. The presence of COPD did not significantly modify the beneficial effect of CABG versus PCI on 10-year all-cause death. Trial registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050 Graphic abstract

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.

Few studies with mixed results have examined the association between chocolate consumption and mortality. We aimed to examine this association in a US population. A population-based cohort of 91891 participants aged 55 to 74 years was identified. Chocolate consumption was assessed via a food frequency questionnaire. Cox regression was used to estimate risk estimates. After an average follow-up of 13.5 years, 19586 all-cause deaths were documented. Compared with no regular chocolate consumption, the maximally adjusted hazard ratios of all-cause mortality were 0.89 [95% confidence interval (CI) 0.84-0.94], 0.84 (95% CI 0.79-0.90), 0.86 (95% CI 0.81-0.93), and 0.87 (95% CI 0.82-0.93) for >0-0.5 servings/week, >0.5-1 serving/week, >1-2 servings/week, and >2 servings/week, respectively (Ptrend = 0.009). A somewhat stronger inverse association was observed for mortality from cardiovascular disease and Alzheimer's disease. A nonlinear dose-response pattern was found for all-cause and cardiovascular mortality (all Pnonlinearity < 0.01), with the lowest risk observed at chocolate consumption of 0.7 servings/week and 0.6 servings/week, respectively. The favorable associations with all-cause and cardiovascular mortality were found to be more pronounced in never smokers than in current or former smokers (all Pinteraction < 0.05). In conclusion, chocolate consumption confers reduced risks of mortality from all causes, cardiovascular disease, and Alzheimer's disease in this US population.

IntroductionTracking progress in reaching global targets for reducing premature mortality from non-communicable diseases (NCDs) requires accurately collected population based longitudinal data. However, most African countries lack such data because of weak or non-existent civil registration systems. We used data from the Nairobi Urban Health and Demographic Surveillance System (NUDSS) to estimate NCD mortality trends over time and to explore the determinants of NCD mortality.MethodsDeaths identified in the NUHDSS were followed up with a verbal autopsy to determine the signs and symptoms preceding the death. Causes of death were then assigned using InSilicoVA algorithm. We calculated the rates of NCD mortality in the whole NUHDSS population between 2008 and 2017, looking at how these changed over time. We then merged NCD survey data collected in 2008, which contains information on potential determinants of NCD mortality in a sub-sample of the NUHDSS population, with follow up information from the full NUHDSS including whether any of the participants died of an NCD or non-NCD cause. Poisson regression models were used to identify independent risk factors (broadly categorized as socio-demographic, behavioural and physiological) for NCD mortality, as well as non-NCD mortality.ResultsIn the total NUHDSS population of adults age 18 and over, 23% were assigned an NCD as the most likely cause of death. There was evidence that NCD mortality decreased over the study period, with rates of NCD mortality dropping from 1.32 per 1000 person years in 2008–10 (95% CI: 1.13–1.54) to 0.93 per 1000 person years in 2014–17 (95% CI: 0.80–1.08). Of 5115 individuals who participated in the NCD survey in 2008, 421 died during the follow-up period of which 43% were attributed to NCDs. Increasing age, lower education levels, ever smoking and having high blood pressure were identified as independent determinants of NCD mortality in multivariate analyses.ConclusionWe found that NCDs account for one-quarter of mortality in Nairobi slums, although we document a reduction in the rate of NCD mortality over time. This may be attributed to increased surveillance and introduction of population-wide NCD interventions and health system improvements from research activities in the slums. To achieve further decline there is a need to strengthen health systems to respond to NCD care and prevention along with addressing social factors such as education.

In aging Caenorhabditis elegans, as in higher organisms, there is more than one cause of death. C. elegans exhibit early death with a swollen, infected pharynx (P death), and later death with pharyngeal atrophy (p death). Interventions that alter lifespan can differentially affect frequency and timing of each type of death, generating complex survival curve shapes. Here, we use mortality deconvolution analysis to investigate how reduction of insulin/IGF‐1 signaling (IIS), which increases lifespan (the Age phenotype), affects different forms of death. All daf‐2 insulin/IGF‐1 receptor mutants exhibit increased lifespan in the p subpopulation (p Age), while pleiotropic class 2 daf‐2 mutants show an additional marked reduction in P death frequency. The latter is promoted by pharyngeal expression of the IIS‐regulated DAF‐16 FOXO transcription factor, and at higher temperature by reduced pharyngeal pumping rate. Pharyngeal DAF‐16 also promotes p Age in class 2 daf‐2 mutants, revealing a previously unknown role for the pharynx in the regulation of aging. Necropsy analysis of daf‐2 interactions with the daf‐12 steroid receptor implies that previously described opposing effects of daf‐12 on daf‐2 longevity are attributable to internal hatching of larvae, rather than complex interactions between insulin/IGF‐1 and steroid signaling. These findings support the view that wild‐type IIS acts through multiple distinct mechanisms which promote different life‐limiting pathologies, each of which contribute to late‐life mortality. This study further demonstrates the utility of mortality deconvolution analysis to better understand the genetics of lifespan., Different daf‐2 insulin/IGF‐1 receptor mutations differentially affect different forms of death in C. elegans. This involves tissue‐ and isoform‐specific action of the DAF‐16 FOXO transcription factor, notably in the pharynx where it protects not only against lethal pharyngeal pathology, but also aging more widely. Thus, wild‐type daf‐2 promotes death from old age through multiple effectors with distinct effects on the various senescent pathologies that cause it.

Background Disease epidemiology of (re-)emerging infectious diseases is changing rapidly, rendering surveillance of travel-associated illness important. Methods We evaluated travel-related illness encountered at EuroTravNet clinics, the European surveillance sub-network of GeoSentinel, between March 1, 1998 and March 31, 2018. Findings 103,739 ill travellers were evaluated, including 11,239 (10.8%) migrants, 89,620 (86.4%) patients seen post-travel, and 2,880 (2.8%) during and after travel. Despite increasing numbers of patient encounters over 20 years, the regions of exposure by year of clinic visits have remained stable. In 5-year increments, greater proportions of patients were migrants or visiting friends and relatives (VFR); business travel-associated illness remained stable; tourism-related illness decreased. Falciparum malaria was amongst the most-frequently diagnosed illnesses with 5,254 cases (5.1% of all patients) and the most-frequent cause of death (risk ratio versus all other illnesses 2.5:1). Animal exposures requiring rabies post-exposure prophylaxis increased from 0.7% (1998-2002) to 3.6% (2013-2018). The proportion of patients with seasonal influenza increased from zero in 1998-2002 to 0.9% in 2013-2018. There were 44 cases of viral haemorrhagic fever, most during the past five years. Arboviral infection numbers increased significantly as did the range of presenting arboviral diseases, Dengue and chikungunya diagnoses increased by 2.6% and 1%, respectively. Interpretation Travel medicine must adapt to serve the changing profile of travellers, with an increase in migrants and persons visiting relatives and friends and the strong emergence of vector-borne diseases, with potential for further local transmission in Europe. Funding This project was supported by a cooperative agreement (U50CK00189) between the Centers for Disease Control and Prevention to the International Society of Travel Medicine (ISTM) and funding from the ISTM and the Public Health Agency of Canada.

Aim of the study Neonatal cholestasis (NC) constitutes a large proportion of pediatric liver disorders. Nevertheless, awareness of the variant etiologies and how to manage them appropriately are lacking. So, out of a few specialized centers, many cases pass without appropriate management. This study aimed to present our tertiary level center's experience in NC that could increase the pediatrician's awareness of handling this problematic and common medical morbidity efficiently. Material and methods It is a retrospective study in which we analyzed the NC cases admitted to the inpatient department within three years. For all recruited patients, the available data were retrieved and recorded. Results A total of 412 patients were reviewed with 20 different etiologies diagnosed. The most common cause was biliary atresia (n = 151, 37%), followed by progressive familial intrahepatic cholestasis (n = 51, 12%), neonatal sepsis (n = 39, 9%), and cytomegalovirus (n = 33, 8%). Of the 412 patients, 394 (81%) had follow-up ranging from 1 to 36 months. A total of 173 patients improved with supportive and/or specific therapy, while 108 patients died at a median age of 6 months. The commonest cause of death was liver failure (40.7%), followed by pneumonia (28.7%), sudden death (13%), septicemia (6.5%), and hepatorenal syndrome (5.5%). Conclusions NC constitutes more than one-third of the inpatient admissions of all pediatric liver disorders and has a high rate of mortality. Awareness of the variety of etiologies and a rapid stepwise approach to diagnosis could have an impact on the outcome of this devastating disease.

Aims To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD). Methods The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD. Results Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08–1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83–1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p-interaction = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11–4.23, p Conclusions The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization. Trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract

To examine the risk for premature mortality and intentional self-harm in autism spectrum disorders (ASD). Based on a national birth cohort. Children born in 1987–2005, diagnosed with ASD by 2007 (n = 4695) were matched with four non-ASD subjects (n = 18,450) and followed until 2015 for mortality and intentional self-harm. The risk among ASD subjects was elevated only for natural cause of death. The risk for intentional self-harm was increased in the unadjusted analyses, but decreased to non-significant after adjusting for comorbid psychiatric disorders. ASD subjects are at increased risk for premature mortality due to natural causes of death. While ASD subjects die of suicide and present with more self-harm, the association is explained by comorbid psychiatric disorders. Electronic supplementary material The online version of this article (10.1007/s10803-020-04768-x) contains supplementary material, which is available to authorized users.

Myocardial infarction (MI) is a major atherosclerotic cardiovascular disease which represents a leading cause of death worldwide. Kruppel-like factor 5 (KLF5) is a member of the kruppel-like transcription factor family which has been reported with pro-apoptotic functions in myocardial cells. This work focuses on the function of KLF5 in the pathogenesis of MI and the molecules involved. A mouse model with MI was established. Hypoxia/reoxygenation (H/R)-treated H9C2 cells were applied for in vitro experiments. A KLF5-specific inhibitor ML264 was administrated in cell and animal models. ML264 significantly reduced apoptosis, expression of fibrosis-related markers, reactive oxygen species in the H/R-treated H9C2 cells, and it reduced myocardial injury, infarct size, apoptosis and fibrosis in the myocardial tissues in model mice through specific downregulation of KLF5. A microRNA (miRNA) microarray analysis was performed, which suggested miR-27a as the most upregulated miRNA in the H/R-treated cells after ML264 treatment. miR-27a mimic reduced apoptosis and fibrosis in H/R-treated cells, while miR-27a inhibition blocked the protective roles of ML264. The integrated bioinformatic analyses and luciferase assays confirmed glutamine fructose-6-phosphate transaminase 2 (GFPT2) mRNA as a target of miR-27a. Overexpression of GFPT2 counteracted the protective functions of miR-27a against MI through the activation of the TGF-β/Smad2/3 signaling pathway. To conclude, this study evidenced that KLF5 possibly induces cell and tissue damage in MI through downregulation of miR-27a and the subsequent activation of GFPT2/TGF-β/Smad2/3 axis. This study may offer novel thoughts into MI treatment.

Introduction Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis. Aim We assessed the prognostic role of SUA in patients with and without MS. Methods We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular mortality (CVM) as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. Results A total of 9589 subjects (median age 58.5 years, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM (> 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p p = 0.004). Cox regression analyses identified an independent association between SUA and CVM (Hazard Ratio: 1.79 [95% CI, 1.15–2.79]; p p Conclusion Increasing SUA levels are associated with a higher CVM risk irrespective of the presence of MS: a cardiovascular SUA threshold may improve risk stratification. Graphic abstract

Background DNA methylation (DNAm) may play a role in age-related outcomes. It is not yet known which DNAm-based biomarkers of age acceleration (BoAA) has the strongest association with age-related endpoints. Methods We collected the blood samples from two independent cohorts: the Normative Ageing Study, and the Cooperative Health Research in the Region of Augsburg cohort. We measured epigenome-wide DNAm level, and generated five DNAm BoAA at baseline. We used Cox proportional hazards model to analyze the relationships between BoAA and all-cause death. We applied the Fine and Gray competing risk model to estimate the risk of BoAA on myocardial infarction (MI), stroke, and cancer, accounting for death of other reasons as the competing risks. We used random-effects meta-analyses to pool the individual results, with adjustment for multiple testing. Findings The mean chronological ages in the two cohorts were 74, and 61, respectively. Baseline GrimAgeAccel, and DNAm-related mortality risk score (DNAmRS) both had strong associations with all-cause death, MI, and stroke, independent from chronological age. For example, a one standard deviation (SD) increment in GrimAgeAccel was significantly associated with increased risk of all-cause death [hazard ratio (HR): 2.01; 95% confidence interval (CI), 1.15, 3.50], higher risk of MI (HR: 1.44; 95% CI, 1.16, 1.79), and elevated risk of stroke (HR: 1.42; 95% CI, 1.06, 1.91). There were no associations between any BoAA and cancer. Interpretation From the public health perspective, GrimAgeAccel is the most useful tool for identifying at-risk elderly, and evaluating the efficacy of anti-aging interventions. Funding National Institute of Environmental Health Sciences of U.S., Harvard Chan-NIEHS Center for Environmental Health, German Federal Ministry of Education and Research, and the State of Bavaria in Germany.

Introduction The public most frequently associates tobacco use solely with pulmonary health risks, despite heart disease being the leading cause of death in smokers. The health perceptions of e-cigarettes, especially cardiovascular health, have not been well studied. We aimed to evaluate the prevalence and health perceptions of tweets related to cardiovascular, pulmonary, and brain health – three organ systems for which tobacco use is a major disease risk factor. Methods We examined the cardiovascular, pulmonary, and brain health perceptions of vaping and JUUL on Twitter, followed by a content analysis of tweets pertaining to the cardiovascular risks. A Twitter firehose API scraped about 6.2 million publicly available tweets from 2015–2019 that contained vaping-related terms, and a separate dataset of about 1.9 million tweets that contained the term JUUL. A quantitative content analysis (n=2145) of tweets was subsequently conducted to assess the health perceptions of vaping and JUUL. Two trained coders independently assessed the posts and Twitter profiles to determine age (

Objectives To describe the epidemiology of granulomatosis with polyangiitis (GPA) in Denmark. To investigate if cardiovascular (CV) related comorbidity and death were increased among Danish AAV patients registered with a diagnosis of granulomatosis with polyangiitis (GPA) in Denmark. To investigate if there was a temporal relation between diagnosis of GPA and CV disease and death. Methods A population-based cohort study was performed using the Danish Civil Registration System, the Danish National Patient Registry and the Danish Cause of Death Register in the period January 1, 1995, to December 31, 2015. Patients registered twice or more with a diagnosis of GPA were included. Annual incidence rate (IR), point prevalence (PP) and standardized mortality rate (SMR) were calculated. The entire adult population in Denmark served as control population. CV morbidity and death caused by CV disease was registered. Results We identified 1829 individuals with GPA. The median annual IR was 20.5/1,000,000 and PP increased from 64 to 277/1,000,000 in 2015. Overall SMR was 2.14. Among patients with GPA 171 had a hospital diagnosis of acute myocardial infarction (AMI). Compared to the control population, the hazard ratio (HR) of AMI was 2.47 (95% CI 1.24–4.94) during the first 3 months after the GPA diagnosis. From 3 months to one year declining to 1.41 (95%CI 0.80–2.49) and after 10 years the HR was still slightly increased to 1.64 (95%CI 1.20–2.23). The risk of a diagnosis of heart failure (HF) was markedly increased with a HR at 7.22 (95% CI 4.55–11.46) during the first 3 months after a GPA diagnosis, after three months up to one year 2.94 (95%CI 1.87–4.69), and 2.07 (95% CI 1.54–2.78) after 10 years. The total number of CV deaths in the GPA cohort was 307. During the first three months after a GPA diagnosis, the HR was increased to 9.51 (95%CI 7.12–12.70) declining to 2.51 (95% CI 1.77–3.58) after one year, but still increased to 1.56 (95% CI 1.23–1.98) after 10 years. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation. Conclusion In a population-based study on GPA, we found stable incidence, increasing prevalence and an overall increased SMR. The risk of CV comorbidity and of CV death among patients with a register diagnosis of GPA was increased., Highlights • This is a nationwide register based study on granolumatosis with polyangiitis in the period 1995–2015. • We found stable incidence, increasing prevalence and increased mortality rate. • Furthermore, we found increased cardiovascular mortality and morbidity especially early in the disease cause. • This is relevant for the initial diagnostic set up regarding these rare patients.

In the last few years, quantitative analysis of metabolites in body fluids using LC/MS has become an established method in laboratory medicine and toxicology. By preparing metabolite profiles in biological specimens, we are able to understand pathophysiological mechanisms at the biochemical and thus the functional level. An innovative investigative method, which has not yet been used widely in the forensic context, is to use the clinical application of metabolomics. In a metabolomic analysis of 41 samples of postmortem cerebrospinal fluid (CSF) samples divided into cohorts of four different causes of death, namely, cardiovascular fatalities, isoIated torso trauma, traumatic brain injury, and multi-organ failure, we were able to identify relevant differences in the metabolite profile between these individual groups. According to this preliminary assessment, we assume that information on biochemical processes is not gained by differences in the concentration of individual metabolites in CSF, but by a combination of differently distributed metabolites forming the perspective of a new generation of biomarkers for diagnosing (fatal) TBI and associated neuropathological changes in the CNS using CSF samples.

This study assessed the association of CD5L and soluble CD36 (sCD36) with the risk of a cardiovascular event (CVE), including CV death and all-cause mortality in CKD. We evaluated the association of CD5L and sCD36 with a predefined composite CV endpoint (unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular accident, congestive heart failure, arrhythmia, peripheral arterial disease [PAD] or amputation by PAD, aortic aneurysm, or death from CV causes) and all-cause mortality using Cox proportional hazards regression, adjusted for CV risk factors. The analysis included 1,516 participants free from pre-existing CV disease followed up for 4 years. The median age was 62 years, 38.8% were female, and 26.8% had diabetes. There were 98 (6.5%) CVEs and 72 (4.8%) deaths, of which 26 (36.1%) were of CV origin. Higher baseline CD5L concentration was associated with increased risk of CVE (HR, 95% CI, 1.17, 1.0-1.36), and all-cause mortality (1.22, 1.01-1.48) after adjusting for age, sex, diabetes, systolic blood pressure, dyslipidemia, waist circumference, smoking, and CKD stage. sCD36 showed no association with adverse CV outcomes or mortality. Our study showed for the first time that higher concentrations of CD5L are associated with future CVE and all-cause mortality in individuals with CKD. This research was supported by grants from the European Foundation for the Study of Diabetes (2014-EFSD-00914) Düsseldorf, Germany; the European Regional Development Fund; and the Carlos III National Institute of Health (PI14/1772) Madrid, Spain. CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM) and CIBER on Liver and Digestive Diseases (CIBEREHD) are an initiative of ISCIII, Madrid, Spain. The NEFRONA study is funded by a research grant from AbbVie, Lake County, Illinois.

Background High resting heart rate (RHR) is associated with increased adverse events. However, the long-term prognostic value in a general population is unclear. We aimed at investigating the impact of RHR, based on baseline as well as time-updated, on mortality in a middle-aged men cohort. Methods A random population sample of 852 men, all born in 1913 was followed from age 50 until age 98 with repeated examinations including RHR during 48 years. The impact of baseline and time-updated RHR on cause-specific mortality was assessed using Cox proportional hazards models and cubic spline models. Results Baseline RHR ≥90 beats per minute (bpm) was associated with higher all-cause mortality as compared to RHR 60–70 bpm (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.17–2.19, P=0.003), but not with cardiovascular (CV) mortality. A time-updated RHR Conclusions In this middle-aged men cohort, a time-updated RHR at 60–70 bpm was associated with lowest CV mortality, suggesting that time-updated RHR could be a useful long-term prognostic index in the general population. RHR and Mortality Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): In recent years, funding has been received from the Swedish state under the agreement between the Swedish government and the county councils relating to the economic support of research and education under the ALF agreement (ALFGBG-721351).

Background Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally, and timely health care seeking is imperative for its prevention, early detection, and management. While online health information–seeking behavior (OHISB) is increasingly popular due to widespread internet connectivity, little is known about how OHISB for COPD has changed in comparison with the COPD disease burden, particularly at a country-specific level. Objective This study aimed to examine the trends in OHISB for COPD and how that compared with the estimates of COPD disease burden in Singapore, a highly wired country with a steadily increasing COPD disease burden. Methods To examine the trends in OHISB for COPD, we performed Prais-Winsten regression analyses on monthly search volume data for COPD from January 2004 to June 2020 downloaded from Google Trends. We then conducted cross-correlational analyses to examine the relationship between annualized search volume on COPD topics and estimates of COPD morbidity and mortality reported in the Global Burden of Disease study from 2004 to 2017. Results From 2004 to 2020, the trend in COPD search volume was curvilinear (β=1.69, t194=6.64, P Conclusions Google search volume on COPD increased from 2007 to 2020; this trend correlated with the upward trajectory of several COPD morbidity estimates, suggesting increasing engagement in OHISB for COPD in Singapore. These findings underscore the importance of making high-quality, web-based information accessible to the public, particularly COPD patients and their carers.

Pancreatic ductal adenocarcinoma (PDA) accounts for 95% of all pancreatic cancers. About 230,000 PDA cases are diagnosed worldwide each year. PDA has the lowest five-year survival rate as compared to others cancers. PDA in Poland is the fifth leading cause of death after lung, stomach, colon and breast cancer. In our paper we have analysed the newest epidemiological research, some of it controversial, to establish the best practical solution for pancreatic cancer prevention in the healthy population as well as treatment for patients already diagnosed with pancreatic cancer. We found that PDA occurs quite frequently but is usually diagnosed too late, at its advanced stage. Screening for PDA is not very well defined except in subgroups of high-risk individuals with genetic disorders or with chronic pancreatitis. We present convincing, probable, and suggestive risk factors associated with pancreatic cancer, many of which are modifiable and should be introduced and implemented in our society.

In Lao People’s Democratic Republic (Lao PDR), the cause of death is not registered in death reports. As a result, the government cannot produce official reports that show mortality according to cause of death. This study aimed to report the underlying cause of death in a tertiary general hospital (Mittaphab Hospital) in Vientiane capital. Mittaphab hospital is a governmental teaching hospital with 300 beds for inpatient services specialized in orthopedics, neurology, and hemodialysis. Since a children hospital exists beside Mittaphab Hospital, severe pediatric cases are referred to the child hospital. HIV-positive cases and sputum positive tuberculosis are also transferred to the other specialized hospitals. All of the subjects in this study were patients who died in 2013–2015 at Mittaphab Hospital. Paper-based medical charts were examined by a medical doctor and staff from the medical records division. This chart review revealed that 1,509 patients (1,006 males and 503 females) died in this hospital during the study period. Of those, the number of patients aged 80 years was small (6.2% and 7.7%, respectively). The most common underlying causes were injury (29.7%), cerebrovascular diseases (26.8%), renal disease (13.3%), infectious diseases (12.4%), and malignant neoplasm including brain tumor (4.8%). Among those aged 20–59 years, these percentages were 37.9%, 23.7%, 12.3%, 10.2%, and 5.0%, respectively. Although the patients visiting the hospital did not represent the whole population, the distribution of cause of death in the hospital was the only available information reported in Lao PDR.

Respiratory pathogens have been detected in forensic investigations using multiple techniques; however, no study has examined the use of automated, nested, multiplex polymerase chain reaction (ANM‐PCR), commonly used in living patients, in the forensic setting. This retrospective study assessed the utility of ANM‐PCR in detecting respiratory pathogens in the pediatric forensic setting. Respiratory samples from 35 cases were tested for up to 20 respiratory pathogens. 51.4% of these cases yielded a positive ANM‐PCR result, 20% of which were considered the cause of or contributory to death. The most commonly detected pathogens were rhinovirus/enterovirus and respiratory syncytial virus, and these were the only pathogens determined to play a significant role in cause of death. The sampled sites and postmortem intervals tested did not affect the likelihood of a positive or negative test. ANM‐PCR panels are effective, affordable, and rapid ancillary tools in evaluating cause of death in the forensic pediatric population.

There are over 850 000 people living with dementia in the UK, with numbers projected to triple by 2050. Dementia prevalence increases with age, affecting 6% of those aged 75–79 years and a third of people over the age of 95 (Knapp & Privette, 2007). Increasing numbers of people will die with dementia and in 2015 dementia became the commonest cause of death in men and women over the age of 80 years (Office for National Statistics, 2017). Deaths due to dementia will increase to around 220,000 deaths per year by 2040 leading to an increased need for palliative care (Etkind, Bone, Gomes et al., 2017). Identifying when people with dementia are reaching the end of their life can be challenging and some studies have attempted to identify prognostic indicators to guide clinicians to adopt a palliative care approach. However, these tools are more reliable at identifying people with dementia at low risk of dying rather than those at higher risk of death (van der Steen, Ooms, van der Wal et al., 2005). So what does palliative care for people with dementia ‘look like’? Definitions of palliative care share a common philosophy, which is an holistic approach, valuing autonomy of patients and families, focussing on dignity, collaborative relationships between healthcare professionals, patients and their families, good communication, and a central goal to maintain quality of life. The European Association for Palliative Care (EAPC) surveyed experts in the field using a Delphi process and published a consensus statement defining the principles of practice for palliative care in dementia (van der Steen, Radbruch, Hertogh et al., 2014). Around this time Dementia UK developed its ‘hospice model’ of Admiral Nursing, of which services are growing. This paper will describe benchmarking of the Admiral Nurse palliative care approach against the domains and recommendations as set out in the EAPC white paper.

Introduction: Cancer of the prostate (PCa) is the second most common cancer-related cause of death among men and the most common non-cutaneous malignancy in Western countries. Numerous papers have been published on the topic of various aspects of this disease; however, rather little has been written on the diagnostic and prognostic value of the prostate cancer obtained from needle biopsy. Aim: To examine the utility of Pixel Prostate software in determining the volume and topographic distribution cancer of the prostate (PCa), and to analyze it with other variables that are characteristic for PCa. Methods: retrospectively, 75 patients data and postoperative prostate specimens were analyzed, after determining topographic distribution and cancer volume (PCa), using PixelProstate software. Results: Mean VPCa was 6.99 cm3 (0.14-29.7; median 4.51), and mean percentage cancer volume relative to prostate volume (%VPCa) was 16% (0.1-67.2%; median 13%). 71% of the patients had T2 stage, while the rest had T3 stage. Apex involvement was present in 65% of the patients, while central zone involvement and extraprostatic extension were present in 23.5% and 22.7% of the patients, respectively. Preoperative Gleason score undergrading was present in 27 (36%) patients, while bilateral PCa finding was increased from 51% to 87%, postoperatively. The most discriminant variable according to the prediction of %VPCa>10% had preoperative bilateral needle biopsy findings, with AUC of 0.75 (

Background: Autopsy rates in neonatal intensive care unit (NICU) patients who died are declining worldwide. Postmortem magnetic resonance imaging (MRI) is suggested as adjunct to or substitute for autopsy. Objective: The aim of this paper was to determine the additional diagnostic value of autopsy in NICU patients and whether autopsy findings were potentially detectable using postmortem MRI. Methods: From 2008 to 2015, 298 infants died during admission to our NICU. Permission for unrestricted, nonforensic autopsy was obtained in 100 (33.6%) of these 298 infants. Retrospectively, autopsy reports and medical records of NICU patients were compared. Additional autopsy findings were graded according to the Goldman system, grading the clinical relevance of additional findings. In addition, the potential detectability of these additional findings on postmortem MRI was assessed. Results: Additional findings obtained by autopsy were found in 48% of the cases, divided into major (Goldman I/II, 24%) and minor (Goldman III/IV, 24%) additional findings. Major additional findings were significantly more often found in patients with a lower gestational age, and minor additional findings in patients with a higher postnatal age at death. Of all patients with additional findings determined by autopsy, 56.3% would most likely not have been detected using postmortem MRI. Conclusions: Our results emphasize the still very important role of autopsy in the NICU setting and show that conventional autopsy could probably not be completely substituted by postmortem MRI.

CRC (Colorectal cancer) is one of the most common causes of death worldwide and in the US (United States). In this study, we aim to perform a population-based analysis on the cause of death among patients with CRC in the US. A total of 834,510 CRC patients diagnosed between 1975 and 2016 in the US were selected from the SEER (Surveillance, Epidemiology, and End Results) program. Causes of death among CRC patients were characterized and SMRs (standardized mortality ratios) of death from non-cancer causes were calculated. Among all CRC patients included in this study, a total of 531,507 deaths were recorded, of which 51.3% were due to CRC, 10.3% were due to other cancers, and 38.4% were due to non-cancer causes. Recently, there has been a relative decrease in index-cancer deaths and an increase in non-cancer causes among CRC patients. The mortality risk from non-cancer rises with accumulating age and longer follow-up time. Cardiovascular diseases are the most prevalent non-cancer causes, accounting for 20.3% of all deaths among CRC patients. Compared with the general population, the mortality rate of non-cancer deaths among CRC patients is doubled (SMR, 2.02; 95% confidence interval, 2.01-2.03).

Background: B-type natriuretic peptide (BNP) is a well-known predictor for prognosis in patients with cardiac and renal diseases. However, there is a lack of studies in patients with advanced hepatic disease, especially patients who underwent liver transplantation (LT). We evaluated whether BNP could predict the prognosis of patients who underwent LT. Material and Methods: The data from a total of 187 patients who underwent LT were collected retrospectively. The serum levels of BNP were acquired at four time points, the pre-anhepatic (T1), anhepatic (T2), and neohepatic phases (T3), and on postoperative day 1 (T4). The patients were dichotomized into survival and non-survival groups for 1-month mortality after LT. Combined BNP (cBNP) was calculated based on conditional logistic regression analysis of pairwise serum BNP measurements at two time points, T2 and T4. The area under the receiver operating characteristic curve (AUROC) was analyzed to determine the diagnostic accuracy and cut-off value of the predictive models, including cBNP. Results: Fourteen patients (7.5 %) expired within one month after LT. The leading cause of death was sepsis (N = 9, 64.3 %). The MELD and MELD-Na scores had an acceptable predictive ability for 1-month mortality (AUROC = 0.714, and 0.690, respectively). The BNPs at each time point (T1 - T4) showed excellent predictive ability (AUROC = 0.864, 0.962, 0.913, and 0.963, respectively). The cBNP value had an outstanding predictive ability for 1-month mortality after LT (AUROC = 0.976). The optimal cutoff values for cBNP at T2 and T4 were 137 and 187, respectively. Conclusions: The cBNP model showed the improved predictive ability for mortality within 1-month of LT. It could help clinicians stratify mortality risk and be a useful biomarker in patients undergoing LT.

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern. The current study aims to explore whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with the development of death in patients with COVID-19. A total of 131 patients diagnosed with COVID-19 from 13 February 2020 to 14 March 2020 in a hospital in Wuhan designated for treating COVID-19 were enrolled in the current study. These 131 patients had a median age of 64 years old (interquartile range: 56–71 years old). Furthermore, among these patients, 111 (91.8%) patients were discharged and 12 (9.2%) patients died in the hospital. The pooled analysis revealed that the NLR at admission was significantly elevated for non-survivors, when compared to survivors (P< 0.001). The NLR of 3.338 was associated with all-cause mortality, with a sensitivity of 100.0% and a specificity of 84.0% (area under the curve (AUC): 0.963, 95% confidence interval (CI) 0.911–1.000;P< 0.001). In view of the small number of deaths (n= 12) in the current study, NLR of 2.306 might have potential value for helping clinicians to identify patients with severe COVID-19, with a sensitivity of 100.0% and a specificity of 56.7% (AUC: 0.729, 95% CI 0.563–0.892;P= 0.063). The NLR was significantly associated with the development of death in patients with COVID-19. Hence, NLR is a useful biomarker to predict the all-cause mortality of COVID-19.

The aim of this study was to evaluate the clinical features and prognostic factors of elderly patients with metastatic pancreatic cancer. Patients diagnosed with metastatic pancreatic cancer between 2004 and 2014 were identified from the Surveillance Epidemiology and End Results database. Clinical characteristics and prognostic factors in elderly patients with metastatic pancreatic cancer were examined. A total of 10784 metastatic pancreatic cancer patients between 65 and 80 years old were included and divided into three age groups. Elderly metastatic pancreatic cancer patients differed from younger patients in many aspects, including marital status, race, sex, T stage, N stage, treatment regimen, prognosis, cause of death, and metastatic characteristics (P

Background By law, covid-19 disease and deaths in workers may lead to coroners’ inquests and/or Health and Safety Executive (HSE) investigations. Aims This study assesses the adequacy of these statutory means to yield recommendations for prevention of acquiring covid-19 infection from work. Methods Covid-19 guidance from the chief coroner and the HSE was appraised, including using Office for National Statistics (ONS) data. Practitioners were asked to estimate the likelihood that covid-19 disease may have arisen from ‘near-miss’ scenarios. Data from the judiciary and the HSE were analysed. Results The coroners’ guidance allowed a wider range of reports of death than did the HSE and conformed better with ONS data on covid-19 mortality by occupation. In the practitioner survey, 62 respondents considered a higher likelihood that reported covid-19 cases would have arisen from the scenario deemed unreportable as a ‘dangerous occurrence’ by HSE than the reportable scenario (P < 0.001). On average there was only one coroner’s report to prevent future death from occupational disease every year in England and Wales. The HSE dealt with a yearly average of 1611 reports of work-related disease including 104 on biological agents, but has received about 9000 covid-19 reports. Conclusions Current HSE guidance for reporting work-related covid-19 may miss many thousands of cases and needs further iteration. Coroners have very limited experience of inquiry into occupational disease caused by biological agents compared with the HSE. Concerns regarding national policy such as on protective equipment warrant a full public inquiry.

In some studies, electrocardiographic early repolarization pattern (ERP) has been associated with an increased risk of death from cardiac causes. However, little is known about the prognostic significance of ERP in the middle-aged and geriatric general populations. We investigated the prevalence and long-term prognostic significance of early repolarization pattern (ERP) on electrocardiograms (ECGs) in the Healthy Aging Longitudinal Study (HALST) cohort of 4615 middle-aged and geriatric community-dwelling Han Chinese adults from Taiwan. The study subjects were followed-up for 95±22 months. A positive ERP of ≥0.1 mV was observed in 889 (19.3%) of the subjects. Kaplan-Meier survival curve analysis showed that ERP was not associated with all-cause and cardiovascular mortality (log-rank test, P=0.13 and 0.84, respectively). Cox regression analysis after adjusting for covariables revealed that age, blood pressure, smoking, diabetes, stroke, chronic kidney disease, and corrected QT interval (QTc) were associated with increased risk of all-cause mortality (P

Deaths caused by traumatic brain injury (TBI) increase in incidence every year worldwidely, mainly in developing countries. Thus, World Health Organization (WHO) estimates that in 2020, TBI will become the third main cause of death. In our study, we evaluated the deaths caused by TBI recorded within the Institute of Forensic Medicine of Craiova, Romania, between 2011 and 2017. Therefore, according to age, the cases were divided into two groups: people aged 0-18 years old (including 18 years old) and people aged over 18 years old (a total of 1005 cases, of which 971 were adults and 34 included in the age group 0-18 years old). In both groups, most patients were males from the rural area. In adults, falling was the main legal entity of the cases, followed by car accidents (which were the most common in children). In both groups, in car accidents, most of them were pedestrians and car occupants. Various aggressions (human, animal, self-injury) were found in 94 (9.68%) of the adult cases and in four (11.76%) cases of children. Another parameter under study was the blood alcohol concentration, being observed that most of the subjects with positive blood alcohol content died from car accidents. By evaluating the Glasgow Coma Scale (GCS) score as a prognostic factor, most of the subjects presented third and fourth degree coma at admission; still, 5.14% of the adult patients who deceased had GCS score 15 at admission, death occurring probably by developing some intracranial hematomas in time. Regarding the morphology of the lesions, most patients presented various forms of cranial fractures, 185 (19.05%) adults in association with extradural hemorrhages∕hematomas, but also there were four cases with extradural hematomas without any cranial fractures. In children, there was highlighted a single case of extradural hemorrhage under the fracture line. Seventy-eight percent of the adults and 44.12% of children presented subdural hematomas associated with other meningo-cerebral lesions. Also, 83.63% of the adults and 97% of children presented brain contusions. In both groups, brain laceration was observed in approximately 50% of the cases.

Objective Malnutrition is associated with an increased risk of mortality in heart failure (HF) patients. Here, we examined the hypothesis that assessment of energy intake in addition to nutritional status improves the stratification of mortality risk in elderly HF patients. Methods We retrospectively examined 419 HF patients aged ≥ 65 years (median 78 years, 49% female). Nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF), and daily energy intake was calculated from intake during 3 consecutive days before discharge. Results During a median 1.52-year period (IQR 0.96–2.94 years), 110 patients (26%) died. Kaplan–Meier survival curves showed that patients with low tertile of daily energy intake had a higher mortality rate than did patients with high or middle tertile of daily energy intake. In multivariate Cox regression analyses, low daily energy intake was independently associated with higher mortality after adjustment for the model including age, sex, BNP, Charlson Comorbidity Index, history of HF hospitalization, and cachexia in addition to MNA-SF. Inclusion of both MNA-SF and energy intake into the adjustment model improved the accuracy of prediction of the mortality after discharge (continuous net reclassification improvement, 0.355, p = 0.003; integrated discrimination improvement, 0.029, p = 0.003). Results of a fully adjusted dose-dependent association analysis showed that risk of all-cause mortality was lowest among HF patients who consumed 31.5 kcal/kg/day of energy. Conclusions Energy intake during hospital stay is an independent predictor of the mortality in elderly HF patients, and its assessment together with established predictors improves the mortality risk stratification. Graphic abstract

Background Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death and is characterized by a progressive loss of pulmonary function over time with intermittent episodes of exacerbations. Rapid and proactive interventions may reduce the burden of the condition for the patients. Telehealth solutions involving self-tracking of vital parameters such as pulmonary function, oxygen saturation, heart rate, and temperature with synchronous communication of health data may become a powerful solution as they enable health care professionals to react with a proactive and adequate response. We have taken this idea to the next level in the Epital Care Model and organized a person-centered technology-assisted ecosystem to provide health services to COPD patients. Objective The objective is to reveal the nature of COPD by combining technology with a person-centered design aimed to benefit from interactions based on patient-reported outcome data and to assess the needed kind of contacts to best treat exacerbations. We wanted to know the following: (1) What are the incidences of mild, moderate, and severe exacerbations in a mixed population of COPD patients? (2) What are the courses of mild, moderate, and severe exacerbations? And (3) How is the activity and pattern of contacts with health professionals related to the participant conditions? Methods Participants were recruited by convenience sampling from November 2013 to December 2015. The participants’ sex, age, forced expiratory volume during the first second, pulse rate, and oxygen saturation were registered at entry. During the study, we registered number of days, number of exacerbations, and number of contact notes coded into care and treatment notes. Each participant was classified according to GOLD I-IV and risk factor group A-D. Participants reported their clinical status using a tablet by answering 4 questions and sending 3 semiautomated measurements. Results Of the 87 participants, 11 were in risk factor group A, 24 in B, 13 in C, and 39 in D. The number of observed days was 31,801 days with 12,470 measurements, 1397 care notes, and 1704 treatment notes. A total of 254 exacerbations were treated and only 18 caused hospitalization. Those in risk factor group D had the highest number of hospitalizations (16), exacerbations (151), and contacts (1910). The initial contacts during the first month declined within 3 months to one-third for care contacts and one-half for treatment contacts and reached a plateau after 4 months. Conclusions The majority of COPD patients in risk factor group D can be managed virtually, and only 13% of those with severe exacerbations required hospitalization. Contact to the health care professionals decreases markedly within the first months after enrollment. These results provide a new and detailed insight into the course of COPD. We propose a resilience index for virtual clinical management making it easier to compare results across settings.

Cardiovascular disease remains the leading cause of death and morbidity worldwide. Inflammation plays an important role in the development of atherosclerosis and is associated with adverse clinical outcomes in patients after percutaneous coronary interventions. Data on stent elements that lead to excessive inflammatory response, proper identification of high–risk patients, prevention and treatment targeting residual inflammatory risk are limited. This review aims to present the role of inflammation in the context of evolving stent technologies and appraise the potential imaging modalities in detection of inflammatory response and anti-inflammatory therapies.

BackgroundCoding of underlying causes of death from death certificates is a process that is nowadays undertaken mostly by humans with potential assistance from expert systems, such as the Iris software. It is, consequently, an expensive process that can, in addition, suffer from geospatial discrepancies, thus severely impairing the comparability of death statistics at the international level. The recent advances in artificial intelligence, specifically the rise of deep learning methods, has enabled computers to make efficient decisions on a number of complex problems that were typically considered out of reach without human assistance; they require a considerable amount of data to learn from, which is typically their main limiting factor. However, the CépiDc (Centre d’épidémiologie sur les causes médicales de Décès) stores an exhaustive database of death certificates at the French national scale, amounting to several millions of training examples available for the machine learning practitioner.ObjectiveThis article investigates the application of deep neural network methods to coding underlying causes of death.MethodsThe investigated dataset was based on data contained from every French death certificate from 2000 to 2015, containing information such as the subject’s age and gender, as well as the chain of events leading to his or her death, for a total of around 8 million observations. The task of automatically coding the subject’s underlying cause of death was then formulated as a predictive modelling problem. A deep neural network−based model was then designed and fit to the dataset. Its error rate was then assessed on an exterior test dataset and compared to the current state-of-the-art (ie, the Iris software). Statistical significance of the proposed approach’s superiority was assessed via bootstrap.ResultsThe proposed approach resulted in a test accuracy of 97.8% (95% CI 97.7-97.9), which constitutes a significant improvement over the current state-of-the-art and its accuracy of 74.5% (95% CI 74.0-75.0) assessed on the same test example. Such an improvement opens up a whole field of new applications, from nosologist-level batch-automated coding to international and temporal harmonization of cause of death statistics. A typical example of such an application is demonstrated by recoding French overdose-related deaths from 2000 to 2010.ConclusionsThis article shows that deep artificial neural networks are perfectly suited to the analysis of electronic health records and can learn a complex set of medical rules directly from voluminous datasets, without any explicit prior knowledge. Although not entirely free from mistakes, the derived algorithm constitutes a powerful decision-making tool that is able to handle structured medical data with an unprecedented performance. We strongly believe that the methods developed in this article are highly reusable in a variety of settings related to epidemiology, biostatistics, and the medical sciences in general.

Background: Coronary heart disease is a leading cause of death in Indonesia and percutaneous coronary intervention (PCI) is a routinely performed procedure. The aim of this study is to provide real-world insight on the demographics of coronary artery disease and comparison between radial compared to femoral PCI in Indonesia, which performed radial access whenever possible. Methods: This is a prospective cohort study involving 5420 patients with coronary artery disease who underwent PCI at 9 participating centers in the period of January 2017–December 2018. Results: Radial access rate was performed in 4038 (74.5%) patients. Patients receiving femoral access has a higher rate of comorbidities and complex lesions compared to radial access. The incidence of in-hospital mortality, cardiogenic shock, major arrhythmia, and tamponade were higher in femoral group. The incidence of in-hospital mortality was 114 (2.1%). New-onset angina (OR 3.412), chronic renal failure (OR 3.47), RBBB (OR 4.26), LBBB (OR 6.26), left main stenosis PCI (OR 3.58), cardiogenic shock (OR 4.9), and arrhythmia (OR 15.59) were found to be independent predictors of in-hospital mortality. Radial access did not independently affect in-hospital mortality. In propensity-matched cohort, radial access was not associated with lower in-hospital mortality in both bivariable and multivariable model. However, radial access was associated with reduced in-hospital mortality in STEMI subgroup (OR 0.31). Conclusion: Higher rate of adverse events was noted on the femoral access group. However, it might stem from the fact that patients with more comorbidities and complex lesions are more likely to be assigned to femoral access-group. Neither radial or femoral access is superior in terms of in-hospital mortality upon propensity-score matching/multivariable analysis. Keywords: Radial access, Percutaneous coronary intervention, National registry, Indonesia

Tuberculosis (TB) is the leading cause of death among infectious diseases. China has a high burden of TB and accounted for almost 13% of the world's cases of multi-drug resistant (MDR) TB. Spinal TB is one reason for the resurgence of TB in China. Few large case studies of MDR spinal TB in China have been conducted. The aim of this research was to observe the epidemiological characteristics of inpatients with MDR spinal TB in six provinces and cities of China from 1999–2015. This is a multicentre retrospective observational study. Patients' information was collected from the control disease centre and infectious disease database of hospitals in six provinces and cities in China. A total of 3137 patients with spinal TB and 272 patients with MDR spinal TB were analysed. The result showed that MDR spinal TB remains a public health concern and commonly affects patients 15–30 years of age (34.19%). The most common lesions involved the thoracolumbar spine (35.66%). Local pain was the most common symptom (98.53%). Logistic analysis showed that for spinal TB patients, reside in rural district (OR 1.79), advanced in years (OR 1.92) and high education degree (OR 2.22) were independent risk factors for the development of MDR spinal TB. Women were associated with a lower risk of MDR spinal TB (OR 0.48). The most common first-line and second-line resistant drug was isoniazid (68.75%) and levofloxacin (29.04%), respectively. The use of molecular diagnosis resulted in noteworthy clinical advances, including earlier initiation of MDR spinal TB treatment, improved infection control and better clinical outcome. Chemotherapy and surgery can yield satisfactory outcomes with timely diagnosis and long-term treatment. These results enable a better understanding of the MDR spinal TB in China among the general public.

Complete right bundle branch block (CRBBB) occurs in 0.2% to 1.3% of the general population, but its prognostic significance in the geriatric population is unknown. We prospectively investigated the prevalence and prognostic value of CRBBB in individuals aged ≥65 years in a community-based population in Taiwan. A total of 5,830 community-dwelling individuals were prospectively recruited from 7 regions across Taiwan starting in December 2008 through March 2013. Those aged ≥65 years were included in the analysis (N=3,383). All subjects underwent a home visit and standardized medical exams and were followed up annually until the end of April 2019; cause of death was documented by citizen death records. The mean age of the study cohort was 73.5±5.9 years (65-104), and 47.21% were men. Among these individuals, 171 (5.05%) had CRBBB; the prevalence was higher in men (7.08%) than in women (3.25%). Subjects with CRBBB were older than those without CRBBB (75.4±6.5 vs. 73.4±5.9), and the frequency of CRBBB increased with age. Survival analysis revealed that all-cause mortality and cardiac mortality were similar in individuals with and without CRBBB during a mean follow-up of 92.6±23.6 months. CRBBB is not associated with increased risk of mortality in the geriatric population.

The spatial synoptic classification (SSC) is a holistic categorical assessment of the daily weather conditions at specific locations; it is a useful tool for assessing weather effects on health. In this study, we assessed (a) the effect of hot weather types and the duration of heat events on cardiovascular and respiratory mortality in summer and (b) the effect of cold weather types and the duration of cold events on cardiovascular and respiratory mortality in winter. A time-stratified case-crossover design combined with a distributed lag nonlinear model was carried out to investigate the association of weather types with cause-specific mortality in two southern (Skåne and Stockholm) and two northern (Jämtland and Västerbotten) locations in Sweden. During summer, in the southern locations, the Moist Tropical (MT) and Dry Tropical (DT) weather types increased cardiovascular and respiratory mortality at shorter lags; both hot weather types substantially increased respiratory mortality mainly in Skåne. The impact of heat events on mortality by cardiovascular and respiratory diseases was more important in the southern than in the northern locations at lag 0. The cumulative effect of MT, DT and heat events lagged over 14 days was particularly high for respiratory mortality in all locations except in Jämtland, though these did not show a clear effect on cardiovascular mortality. During winter, the dry polar and moist polar weather types and cold events showed a negligible effect on cardiovascular and respiratory mortality. This study provides valuable information about the relationship between hot oppressive weather types with cause-specific mortality; however, the cold weather types may not capture sufficiently effects on cause-specific mortality in this sub-Arctic region. Electronic supplementary material The online version of this article (10.1007/s00484-020-01921-0) contains supplementary material, which is available to authorized users.

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.

textabstractBackground: Unhealthy diet, especially consumption of trans fatty acids (TFAs), is a known risk factor for cardiovascular disease (CVD), a leading cause of death in Austria. In 2009, Austria introduced a law regulating the content of TFAs in foods. The aim of this study was to assess the impact of the TFA regulation on CVD-related outcomes.Methods: The study evaluated the TFA regulation as an intervention in a natural experiment. Two study periods were assessed: pre-intervention (1995-2009) and post-intervention (2010-14). The study compared the age-standardized death rates per 100 000 population for CVD outcomes with those of a 'synthetic' international comparator population, created from data of OECD countries where TFA regulation has not been implemented, but where the population is otherwise comparable.Results: There was a continuous decrease in CVD-related mortality throughout the study period in both the synthetic international comparator population, as well as in the adult Austrian population, with no significant change in this trend observed as an effect of TFA regulation.Conclusions: Whilst the results are counterintuitive, given the established link between TFA consumption and an increased risk of CVD, there are many possible explanations: high prevalence of tobacco smoking, changes in TFA content in foods due to international guidance as opposed to formal regulation and a beneficial impact of TFA regulation on sub-groups of the population that might not be detected with nationally aggregated data. However, reduction in TFAs should still be considered an important part of risk factor reduction for CVD and other non-communicable diseases.

Background Tobacco is the leading preventable cause of death globally and tobacco taxation is a cost-effective method of reducing tobacco use in countries and increasing revenue. However, without adequate enforcement some argue the risk of increasing illicit trade in cheap tobacco makes taxation ineffective. We explore this by testing sub-national variations in the impact of tobacco tax increases from 2009 to 2011, on seven smoking-related diseases in adults in Romania, to see if regions that are prone to cigarette smuggling due to bordering other countries see less benefit. Method We use a pragmatic natural experiment study approach to analyse the study period 2009–15. Findings from hospital episodes data relating to smoking-attributable diseases are analysed for six regional subgroups which are compared according to border characteristics with other countries. Results At a national level smoking-attributable diseases reduced over the study period especially around the tax increase years, with asthma showing the most significant decline. Sub-nationally there was no statistically significant correlation in variations between central regions and those bordering other countries. Conclusion There is a reassuring decline in hospitalizations for smoking-related diseases associated with the tax increases, and no sub-national association with smuggling risk measured by variation in the size of this effect and regions that border other countries. More comprehensive and progressive tobacco control in Romania should be implemented in line with the WHO Framework Convention for Tobacco Control.

Telomere length (TL) is considered an indicator of aging and age-related diseases, but longitudinal studies on TL changes and mortality are few. We therefore analyzed TL and longitudinal changes in TL in relation to all-cause, cardiovascular, and cancer mortality in 247 elderly Swedish men. TL was determined by the qPCR method at ages 71 and 81 and subsequent mortality cases were identified from the Swedish cause-of-death registry. Cox proportional hazard ratios were calculated during a mean follow-up of 7.4 years, during which 178 deaths occurred. Short telomeres at baseline was strongly associated with mortality risks, with a 40 to 70% increased risk of all-cause mortality, and a 2-fold increased risk of cancer mortality. Longitudinal changes in TL revealed shortening in 83% of individuals, whilst 10% extended their telomeres. TL attrition did not predict all-cause or cancer mortality, but we found a 60% decreased risk for cardiovascular mortality in those who shortened their telomeres. Our data show an increased risk of mortality in individuals with short baseline telomeres, but no relations to all-cause, and cancer mortality for changes in TL. Intriguingly, our data indicate lower risk of cardiovascular mortality with shortening of telomeres. The latter should be interpreted cautiously.

Metabolic syndrome is a critically important precursor to the onset of many diseases, such as cardiovascular disease, and cardiovascular disease is the leading cause of death worldwide. The primary risk factors of metabolic syndrome include hyperglycaemia, abdominal obesity, dyslipidaemia, and high blood pressure. It has been well documented that metabolic syndrome alters vascular endothelial and smooth muscle cell functions in the heart, brain, kidney and peripheral vessels. However, there is less information available regarding how metabolic syndrome can affect pulmonary vascular function and ultimately increase an individual's risk of developing various pulmonary vascular diseases, such as pulmonary hypertension. Here, we review in detail how metabolic syndrome affects pulmonary vascular function. [Image: see text]