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The pandemic of coronavirus disease (COVID)-19 is a global threat, causing high mortality, especially in the elderly. The main symptoms and the primary cause of death are related to interstitial pneumonia. Viral entry also into myocardial cells mainly via the angiotensin converting enzyme type 2 (ACE2) receptor and excessive production of pro-inflammatory cytokines, however, also make the heart susceptible to injury. In addition to the immediate damage caused by the acute inflammatory response, the heart may also suffer from long-term consequences of COVID-19, potentially causing a post-pandemic increase in cardiac complications. Although the main cause of cardiac damage in COVID-19 remains coagulopathy with micro- (and to a lesser extent macro-) vascular occlusion, open questions remain about other possible modalities of cardiac dysfunction, such as direct infection of myocardial cells, effects of cytokines storm, and mechanisms related to enhanced coagulopathy. In this opinion paper, we focus on these lesser appreciated possibilities and propose experimental approaches that could provide a more comprehensive understanding of the cellular and molecular bases of cardiac injury in COVID-19 patients. We first discuss approaches to characterize cardiac damage caused by possible direct viral infection of cardiac cells, followed by formulating hypotheses on how to reproduce and investigate the hyperinflammatory and pro-thrombotic conditions observed in the heart of COVID-19 patients using experimental in vitro systems. Finally, we elaborate on strategies to discover novel pathology biomarkers using omics platforms.

Coronary heart disease (CHD) is the leading cause of death and disability worldwide. Despite current therapy, the morbidity and mortality for patients with CHD remains significant. The most important manifestations of CHD arise from acute myocardial ischaemia-reperfusion injury (IRI) in terms of cardiomyocyte death and its long-term consequences. As such, new therapeutic interventions are required to protect the heart against the detrimental effects of acute IRI and improve clinical outcomes. Although a large number of cardioprotective therapies discovered in pre-clinical studies have been investigated in CHD patients, few have been translated into the clinical setting, and a significant number of these have failed to show any benefit in terms of reduced myocardial infarction and improved clinical outcomes. Because of this, there is currently no effective therapy for protecting the heart against the detrimental effects of acute IRI in patients with CHD. One major factor for this lack of success in translating cardioprotective therapies into the clinical setting can be attributed to problems with the clinical study design. Many of these clinical studies have not taken into consideration the important data provided from previously published pre-clinical and clinical studies. The overall aim of this ESC Working Group Cellular Biology of the Heart Position Paper is to provide recommendations for optimizing the design of clinical cardioprotection studies, which should hopefully result in new and effective therapeutic interventions for the future benefit of CHD patients.

Introduction Every year there is an increase in the number of cases and deaths due to the majority of cancers. Currently, these diseases constitute the second cause of death in Poland and the USA. The number of cases of malignant neoplasms in Poland has more than doubled over the last three decades. According to the National Cancer Registry, in Poland about 95.5 people per thousand die every year from malignant neoplasms. Current epidemiological data on cancer is worrying because the World Health Organization predicts a significant increase in the incidence of cancer in the general population. This problem, which is significant on the global scale, demands the search for more effective prevention methods so that more and more attention is paid to both primary and secondary prevention. Prevention and early detection of cancer have become a priority for the national health policy of many European countries. Numerous studies around the world prove that reducing the risk of cancer is most effective through adopting a healthy lifestyle, avoiding exposure to carcinogens, combined with regular screening. Objective The aim of the study was to review knowledge on cancer prevention, including the latest research results. Conclusions Due to the systematic increase in the incidence of cancer, a strong emphasis should be placed on prevention. Preventive actions bring benefits not only to the individual, but are an important aspect of health policy. The importance of primary prevention in relation to healthy people has been demonstrated, including secondary prevention aimed at controlling risk factors in relation to persons exposed to them. The combination of these activities becomes an important element in maintaining the health of the individual, as well as society.

Objectives: The objective of the present study was to investigate the risk of death from non-malignant diseases in female pulp and paper workers in Norway. Methods: A total of 3143 women first employed between 1920–93 were included in the study cohort. Information about each cohort member was obtained from personnel record files in the mills in order to identify employment periods and job categories. Data on cause and date of death were added by linkage to the Cause of Death Register using unique personal identification numbers. The follow up period was 1951–2000. Standardised mortality ratios (SMRs) with 95% confidence intervals (95% CIs) were calculated using the national female mortality rates as reference. Poisson regression analysis was used to examine internal relations between the duration of employment in paper departments and the risk of death from selected causes. Relative risks (RRs) and 95% CIs were calculated. Results: The study showed a significantly increased risk for total non-malignant mortality (SMR = 1.14, 95% CI 1.05 to 1.24), mainly due to increased mortality from ischaemic heart disease (SMR = 1.22, 95% CI 1.03 to 1.43) and cerebrovascular diseases (SMR = 1.16, 95% CI 0.94 to 1.42). Analysis by department showed the highest risk of death in paper department workers with short term employment. Internal analyses showed a 5% and 9% increase in risk of dying from ischaemic heart disease and respiratory diseases, respectively, among paper department workers exposed to paper dust. The risk decreased with increasing duration of employment. Conclusion: The increased risk of ischaemic heart diseases and respiratory diseases seen among employees of paper departments may be related to exposure to paper dust.

Item does not contain fulltext There are large variations in the incidence, registration methods and reported causes of sudden cardiac arrest/sudden cardiac death (SCA/SCD) in competitive and recreational athletes. A crucial question is to which degree these variations are genuine or partly due to methodological incongruities. This paper discusses the uncertainties about available data and provides comprehensive suggestions for standard definitions and a guide for uniform registration parameters of SCA/SCD. The parameters include a definition of what constitutes an 'athlete', incidence calculations, enrolment of cases, the importance of gender, ethnicity and age of the athlete, as well as the type and level of sporting activity. A precise instruction for autopsy practice in the case of a SCD of athletes is given, including the role of molecular samples and evaluation of possible doping. Rational decisions about cardiac preparticipation screening and cardiac safety at sport facilities requires increased data quality concerning incidence, aetiology and management of SCA/SCD in sports. Uniform standard registration of SCA/SCD in athletes and leisure sportsmen would be a first step towards this goal.

European journal of nuclear medicine and molecular imaging 43(4), 780-792 (2016). doi:10.1007/s00259-015-3259-3, Published by Springer-Verl., Heidelberg [u.a.]

Overdiagnosis is a growing problem worldwide. Overdiagnosis is the diagnosis of deviations, abnormalities, risk factors, and pathologies that in themselves would never cause symptoms (this applies only to risk factors and pathology), would never lead to morbidity, and would never be the cause of death. Overdiagnosis is often misinterpreted as overutilization or overtreatment. Overutilization, overtreatment, and overdiagnosis are interrelated but three distinct topics. Overutilization (establishment of standard practice that does not provide net benefit) does not have to lead to overdiagnosis or overtreatment, but the risk exists. Treatment of overdiagnosed conditions is one category of overtreatment. Another is when the best available evidence shows that the treatment has no beneficial effect. Overdiagnosis can be caused by overutilization and is nearly always followed by overtreatment. Treating an overdiagnosed condition cannot improve the patient’s prognosis, and therefore can only be harmful. At the individual level, we can never be sure if the person is overdiagnosed. However, experiences and thoughts of individuals who are most likely overdiagnosed can be explored in qualitative interviews, e.g. men with a small screening detected abdominal aortic aneurism. In longitudinal surveys, the degree and length of psychosocial consequences associated with overdiagnosis can be estimated. In high-quality RCTs, the magnitude of overdiagnosis can be quantified, and in cohort studies, we can find indications of overdiagnosis. Finally, we can conduct research about the consequences of overdiagnosis in at least eight different areas: financial strain, hassles/inconveniences, medical costs, opportunity costs, physical harms, psychological harms, societal costs and work-related costs.

Cardiac arrest is a common and treatable cause of death and disability. Each year ≈424 000 people experience emergency medical services (EMS)-assessed out-of-hospital cardiac arrest (OHCA) in the United States.1 The actual burden of OHCA is likely significantly higher because a substantial number go unassessed. In a prospective analysis of deaths in a US county, 5.6% of annual mortality was attributable to cardiac arrest.2 Many patients who suffer OHCA do not receive prompt cardiopulmonary resuscitation (CPR). Among those who receive CPR, a large number do not survive because of an inability to restore spontaneous circulation, or anoxic cerebral injury even after restoration of circulation. Nevertheless, when timely interventions are provided, a small proportion of patients (10.4% of all EMS-treated OHCA) recover to resume normal lives. The key therapeutic interventions that make the difference between life and death, metaphorically characterized as the 5 links in a chain of survival by the American Heart Association, include: (1) immediate recognition of cardiac arrest and activation of the EMS, (2) early CPR with emphasis on chest compression, (3) rapid defibrillation, (4) effective advanced life support, and (5) integrated postcardiac arrest care.3 Resuscitation science has undergone major advances since the origins of modern CPR >50 years ago.4 The field continues to be dynamic with emergence of new therapies such as therapeutic hypothermia5 and improvements in systems of care. However, many questions remain on issues such as optimum compression rate, efficacy of chest compression only CPR (CCCPR), dispatcher-assisted CPR, and benefits of postresuscitation measures such as hypothermia. A critical challenge also lies in the translation of resuscitation science into practice. To improve outcomes, each of the links in the chain of survival needs to be executed promptly and effectively. There remain several lacunae, which need to be overcome to develop an …

A mortality cohort study was undertaken among Polish pulp and paper workers. This paper concentrates on neoplasms mortality among men and women employed continuously for at least one year in the factory producing sulphate pulp, paper board and paper products. A retrospective observation carried out till 31 December 1995 covered 10,460 workers employed during the years 1968-1990. The cohort accessibility was 99%. Cancer risk was evaluated on the basis of standardized mortality ratio (SMR) calculated according to the person-years method. The general population of Poland was the reference population. The results of a 23-year cohort observation, published earlier, showed a lowered overall mortality from all causes and from all malignant neoplasms, and a significant excess of death from peritoneum and prostate cancer among pulp mill male subcohort. The conclusion was drawn that a 'young' cohort and relatively short follow-up period might have affected the results. The results presented in this paper, obtained after further five years of observation showed in the male cohort an excess of deaths from cancer of respiratory tract and peritoneum (lung SMR = 122, nasal cavities SMR = 587, peritoneum SMR = 562). An approximate correction for smoking habits resulted in only 4 decreased risk estimates for lung cancer, indicating a small positive confounding effect of smoking in this material. In female cohort an excess of brain cancer was found (SMR = 355). Only the excess mortality from cancers of nose, lung and peritoneum was coherent with the exposure to higher concentrations of wood dust, pulp, paper and board dust. It may support a hypothesis that these factors as well as dust pollutants, not yet identified in this study, may be considered as one of the risk factors contributing to the incidence of neoplasms of these sites.

A cohort study was designed to evaluate the risk of death from malignant neoplasms among pulp and paper workers. This paper presents the evaluation of death risk among workers engaged only in the production of paper, paperboard and paper products. The cohort study covered 1,322 males and 1,914 females employed for, at least, one year in a big pulp and paper mill during the period 1968-90. The study of exposure to harmful factors revealed that concentrations of paper and paperboard dusts in this mill exceeded hygienic standards. The analysis of death risk by causes and gender of those under study was based on standardized mortality rate (SMR) calculated using the method of person-year observation. The general population of Poland was used as reference. The results do not confirm excess mortality from lung, stomach and hematopoietic cancers in paper mill workers reported by other authors. However, an elevated risk of bladder cancer in males (SMR = 491, two deaths) and brain cancer in females (SMR = 353, two deaths) was observed. Both SMR values were not statistically significant. Because of small number of deaths, risk according to exposure and latency was not evaluated.

Mortality among workers in the Polish pulp and paper industry was evaluated in retrospective cohort study of 10460 workers who had been employed continuously for at least one year between 1968 and 1990 in the factory producing sulphate pulp, paper, board and paper products. A standardized mortality ratio (SMR) analysis was used to compare death rates for the exposure group with Polish national rates. For all the subjects death due to all causes and all malignant neoplasms were lower than the number expected. The only significantly increased risks were those of malignant neoplasm of brain among women (4 cases, SMR = 318) and of retroperitoneum and peritoneum among men (2 cases, SMR = 659), exposed to high level of wood dust and irritant sulphur compounds. The authors could not find any etiological explanation of the excessive mortality from brain and peritoneum cancers.

AMI : acute myocardial infarction ARVC : arrhythmogenic right ventricular cardiomyopathy BrS : Brugada syndrome CACS : coronary artery calcium score CAD : coronary artery disease ChD : Chagas heart disease CMR : cardiac magnetic resonance CPVT : catecholaminergic polymorphic ventricular tachycardia CTCA : computed tomography coronary angiography CV : cardiovascular DCM : dilated cardiomyopathy EAPCR : European Association for Cardiovascular Prevention and Rehabilitation HCM : hypertrophic cardiomyopathy LGE : late gadolinium enhancement LQTS : long QT syndrome LV/RV : left/right ventricle LVH : left ventricle hypertrophy NSVT : non-sustained ventricular tachycardia PPE : preparticipation evaluation PVC : premature ventricular contractions SCA/SCD : sudden cardiac arrest/death TTE : transthoracic echocardiography VF : ventricular fibrillation VT : ventricular tachycardia Sudden cardiac death (SCD) associated with athletic activity is a rare but devastating event. Victims are usually young and apparently healthy, and while many of these deaths remain unexplained, a substantial number of victims harbour an underlying and potentially detectable cardiovascular (CV) disease.1–4 The vast majority of these events are due to malignant tachyarrhythmias, usually ventricular fibrillation (VF) or ventricular tachycardia (VT) degenerating into ventricular fibrillation (VF), occurring in individuals with arrhythmogenic disorders (e.g. hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, channelopathies). Intensive exercise training and competitive sport participation is a trigger that may favour insurgence of ominous ventricular tachyarrhythmias in predisposed individuals.5 Consequently, there is a great interest in early identification of at-risk individuals for whom appropriate treatment, followed or not by physical activity adjustment, may be implemented to minimize the risk of SCD. However, the role of pre-participation evaluation (PPE) in athletes as a feasible and efficient strategy to identify individuals at risk has remained controversial. …

Each year in the United States, approximately 800 000 men and women are affected by stroke, which equates to one incident of stroke every 40 seconds.1 Stroke is the fourth leading cause of death nationally and is one of the foremost contributors to functional disability.2 The cost to the US healthcare system is substantial. Specifically, in 2010 medical treatment for stroke cost approximately $54 billion and is expected to exceed $1 trillion by 2050.3 The burden of stroke is not limited to US alone; mortality from stroke is responsible for ~9% of all deaths worldwide and is the second most common cause of death following ischemic heart disease.4 While the overall risk of stroke has declined by 25% in the last decade,5 disability from stroke is now emerging as a major public health problem, particularly in the elderly, as we observe an increase in aging of the population. Accordingly, in this month’s topic review in Circulation: Cardiovascular Quality and Outcomes , we concentrate on contemporary issues around stroke and transient ischemic attack (TIA). Significant knowledge and practice gaps continue to exist across the continuum of stroke care. First, risk factor modification for stoke remains suboptimal. The most important modifiable risk factor for prevention of stroke is hypertension (HTN), with the lowering of blood pressure associated with a more than 25% reduction in the relative risk (RR) of stroke.6,7 Modification of other risk factors such as diabetes, hypercholesterolemia, smoking cessation and atrial fibrillation (AF),8 have also been shown to reduce the incidence of stroke.9 However, appropriate identification of patients at risk and ensuring adherence to prevention strategies presents many challenges. For example, numerous patients with HTN are not on therapy and many of those who are treated have suboptimal blood pressure …

Cardiovascular disease (CVD) in women has been historically understudied. For many years, heart disease had been thought to be primarily a “man’s disease.” Consequently, women have been significantly under-represented in longitudinal studies of disease history and in clinical trials. High-quality data from women at the extremes of age, with multiple co-morbidities, and from racial and ethnic minorities have been particularly rare. In order to increase awareness of cardiovascular prevention among women, in 1999 the American Heart Association (AHA) published its first women-specific clinical recommendations for the prevention of CVD.1 In 2004, the AHA and multiple other collaborating organizations subsequently sponsored “Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women,” which underwent updates in 2007 and 2011. As a result of these and other related initiatives, the rate of public awareness of CVD as the leading cause of death among US women has increased from 30% in 1997 to 54% in 2009.2 CVD-associated death among US women has declined significantly over this time period.3,4 Yet substantial work still needs to be done to improve women’s cardiovascular health. CVD remains the number one killer among women.4 As the obesity epidemic continues, we are actually finding increases in coronary heart disease (CHD) death among young women 35 to 54 years of age.2 Morbidity and mortality from stroke and hypertension remain high.4 In addition, substantial outcomes disparities continue for women from racial and ethnic minorities.4 We have therefore dedicated our topic summaries in this issue of Circulation: Cardiovascular Quality and Outcomes to CVD in women. We have included only those studies where authors provided a convincing a priori reason to study a particular disease process or clinical intervention in women and reported primary endpoints that were sex-specific. We have included articles on the representation of women …

Mortality among workers in the Finnish pulp and paper industry was evaluated in a retrospective cohort study of 3520 workers who had been employed continuously for at least one year between 1945 and 1961. Six subcohorts were formed according to six work areas: sulphite, sulphate, paper, and board mills, maintenance department, and power plant. National mortality rates were used for comparison. The mortality of a cohort of 1290 sawmill workers was also studied in order to have a socially, geographically, and occupationally similar group without the exposures typical of the pulp and paper industry for comparison. Smoking habits were surveyed. Mortality was followed up until 31 December 1981. Overall mortality for the entire cohort did not differ from that expected (1044 obs, 1029.4 exp, SMR 101), but there was an excess of deaths from diseases of the circulatory system among the men (489 obs, 404.9 exp, SMR 121). This was due to the excess of deaths from ischaemic heart disease found among the men at the sulphite, sulphate, and paper mills, maintenance department, and power plant, but not at the sawmill. The existing smoking data did not explain this finding and it may therefore be associated with occupational exposures.

The different studies published and indexed in Medline and in the Spanish Medical Index (IME) from 1984 up to 1998 (IME: 1971-1996) are reviewed. To start with, an assessment was made of the number of publications put out which have to do with the impact of pollution on human health as well as the percentage thereof which analyze the mortality as a health indicator. Afterward, the original works published within the January 1994-June 1998 period were reviewed in detail. Most of the original articles are combined time series studies which analyze, on a single-day basis, the relationship between the levels of pollution and the mortality for non-accidental causes. Other original articles were also summarized based on an approach other than the time series one, highlighting different cohort studies which relate the levels of pollution to the mortality on an individual level and which confirm the findings of prior ecological studies. The pollutants analyzed most often are the different types of particles, although studies are also common regarding the impact of sulfur dioxide, nitrogen dioxide, ozone and carbon monoxide. The method of analysis most used is the Poisson regression, into which different confusion variables bearing an impact thereon such as seasonality and tendency, temperature and relative humidity and day of the year are basically added. In the studies reviewed, the positive significant findings prevail, being consistent especially for particles, which is the pollutant most analyzed. The articles studying other pollutants, although fewer in number, also indicate a significant relationship between pollution levels and the mortality.

Mortality among workers in the Finnish pulp and paper industry was evaluated in a retrospective cohort study of 3520 workers who had been employed continuously for at least one year between 1945 and 1961. Six subcohorts were formed according to six work areas: sulphite, sulphate, paper, and board mills, maintenance department, and power plant. National mortality rates were used for comparison. The mortality of a cohort of 1290 sawmill workers was also studied in order to have a socially, geographically, and occupationally similar group without the exposures typical of the pulp and paper industry for comparison. Smoking habits were surveyed. Mortality was followed up until 31 December 1981. Overall mortality for the entire cohort did not differ from that expected (1044 obs, 1029.4 exp, SMR 101), but there was an excess of deaths from diseases of the circulatory system among the men (489 obs, 404.9 exp, SMR 121). This was due to the excess of deaths from ischaemic heart disease found among the men at the sulphite, sulphate, and paper mills, maintenance department, and power plant, but not at the sawmill. The existing smoking data did not explain this finding and it may therefore be associated with occupational exposures.

Background The second coronavirus disease (COVID-19) epidemic wave in the UK progressed aggressively and was characterised by the emergence and circulation of variant of concern alpha (VOC 202012/01). The impact of this variant on in-hospital COVID-19-specific mortality has not been widely studied. We aimed to compare mortality, clinical characteristics, and management of COVID-19 patients across epidemic waves to better understand the progression of the epidemic at a hospital level and support resource planning. Methods We conducted an analytical, dynamic cohort study in a large hospital in South London. We included all adults (≥ 18 years) with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who required hospital admission to COVID-19-specific wards between January 2020 and March 2021 (n = 2701). Outcome was COVID-19-specific in-hospital mortality ascertained through Medical Certificate Cause of Death. Results In the second wave, the number of COVID-19 admissions doubled, and the crude mortality rate dropped 25% (1.66 versus 2.23 per 100 person-days in second and first wave, respectively). After accounting for age, sex, dexamethasone, oxygen requirements, symptoms at admission and Charlson Comorbidity Index, mortality hazard ratio associated with COVID-19 admissions was 1.62 (95% CI 1.26, 2.08) times higher in the second wave. Conclusions Although crude mortality rates dropped during the second wave, the multivariable analysis suggests a higher underlying risk of death for COVID-19 admissions in the second wave. These findings are ecologically correlated with an increased circulation of SARS-CoV-2 variant of concern 202012/1 (alpha). Availability of improved management, particularly dexamethasone, was important in reducing risk of death.

Background and aim Pneumonia remains one of the most frequent death causes worldwide. Among the etiological factors S. pneumoniae-causing lobar pneumonia plays a leading role. According to current textbook knowledge at least three sequential stages of lobar pneumonia are distinguished: congestion, red hepatization and gray hepatization. However, there are no detailed data supporting this stage concept. There are also controversial views on its etiology. In this study, the lung changes in lobar pneumonia were related to the cause and duration of the disease. In addition, the complications of the disease were evaluated. PCR studies verified the etiology of pneumonia. Material and methods Lobar pneumonia was analyzed in 252 post mortem cases examined in a large hospital in Irkutsk. The pathology, etiology of pneumonia, course of disease and cause of death were recorded and correlated to its clinical course and duration. In the second part of the study, the results in 95 patients were analyzed in detail and related to PCR findings. Results Most patients were adult men of low social status who showed signs of severe alcoholism. Lobar pneumonia was observed in 85% of the patients, while the remaining patients showed sublobar (“lobular”, focal) lung involvement. Histologically, three patterns of inflammation were observed, which in most patients occurred concurrently in different parts of the involved lobe: “congestion”, characterized by serous exudation with multiple cocci (41% of cases), “red hepatization” (41% of cases) and “gray hepatization” (100% of cases). The latter pattern was subdivided into three subgroups according to the ratio of fibrin—neutrophils and the presence of macrophages. The mean number of different histological patterns observed per patient was 3.8. There was no correlation between the inflammatory patterns and the duration of the disease. In 23% of the patients, the cause of death was of pulmonary origin, while the remaining patients died of extrapulmonary complications (i.e. acute heart failure 26%, acute vascular insufficiency 15% purulent meningitis 11–24.3%. In 29/95 patients (20 with lobar and 9 with focal pneumonia) pneumococcal etiology of pneumonia was established by PCR. Conclusion Lobar pneumonia is a distinct clinico-pathological entity caused by S. pneumoniae, demonstrated by PCR testing and/or cytological examinations. Bacteriologic studies frequently give falsenegative results. Lobar pneumonia is characterized by three main histopathological patterns (congestion or microbeous edema, and red and gray hepatization) which usually occur side by side and not in chronological order. Early death is often related to heart failure and septic shock, while meningitis is a frequent complication later in the course.

Children are known to be better protected from COVID-19 than adults, but their susceptibility patterns and the risk relative to other diseases are insufficiently defined. Here, we found that the COVID-19 mortality rate is U-shaped in childhood: it initially decreases, reaching the minimum at the ages 3-10 years, and then increases throughout life. All-cause mortality and mortality from other diseases, such as pneumonia and influenza, show a similar pattern; however, childhood mortality rates from COVID-19 are considerably lower than from other diseases, with the best relative protection achieved at the youngest ages. Consistent with this, the fraction of COVID-19 deaths among all deaths increases as a function of age throughout childhood and the entire life. We discuss implications of the elevated postnatal COVID-19 risk and lower childhood COVID-19 mortality compared to other diseases.

Introduction Tobacco is the leading cause of death and disease in India. This study examines the effect of training intervention in behavioral counseling on intention to quit tobacco in primary healthcare settings in India. The intervention included training to improve behavioral counseling practices of primary care physicians (PCPs) based on the 5As approach to increase patients' motivation to quit tobacco. Methods A quasi-experimental design was used for the study. The intervention consists of training of primary care physicians in the behavioral intervention in tobacco cessation. The intervention was conducted in twelve districts of two states in India (Rajasthan and Odisha) in 2016-2017. Four districts were randomly sampled for the study. A total of 1314 participants (intervention and control) were recruited for the study in the baseline and end-line surveys, respectively. Intention to quit in 30 days was the primary outcome measure. Difference-in-difference (DiD) logistic regression models were used separately for smokers and smokeless tobacco users to estimate the odds of intention to quit. Analysis was done in STATA Version 14. Results The intervention and time variable had a significantly positive influence on the intention to quit tobacco among smokers. Smokers in the intervention districts had higher odds of intention to quit (OR=9.82; 95% CI: 1.67-57.72) compared to smokers in the control districts. Smokeless tobacco (SLT) users had higher odds of intention to quit (OR=3.06; 95% CI: 1.35-6.98) in the end-line survey compared to baseline survey. Conclusions Our findings indicate that building capacity in behavioral intervention in primary care settings can help increase the intention to quit among smokers. The observed difference in intention to quit between smokers and SLT users suggests the need of tailored counseling interventions for SLT users. There is a need for further research to design and evaluate training and behavioral interventions for SLT and dual (smoking and SLT) users in primary care settings in low- and middle-income countries.

Introduction: Falls are a leading cause of death among Chinese oldest olds. However, studies on Chinese community-dwelling older adults are lacking. We aimed to identify the associations of falls and severe falls with blood pressure and frailty among Chinese community-dwelling oldest olds. Methods: Cross-sectional analyses were conducted with 6,595 community-dwelling oldest olds (aged ≥80 years) from 22 Chinese provinces from the Chinese Longitudinal Health and Longevity Study (CLHLS). Systolic BP (SBP) and diastolic BP (DBP) were measured twice at participants’ homes, and a 38-item frailty index was used to assess the frailty status of participants. Falls and severe falls were confirmed through face-to-face interviews. Multivariate logistic regression was used to investigate the associations of BP and frailty with falls and severe falls. Results: The mean participant age was 91.0 years, and 56.1% were female. In total, 24.2% participants had a history of fall and 8.3% had a history of severe falls. The multivariate-adjusted odds ratio (OR) for falls among the oldest old with SBP ≥140 mm Hg compared to those with an SBP of 120–129 mm Hg was 1.20 (95% confidence interval [CI], 1.01–1.44). The adjusted OR for falls among frail participants compared to robust participants was 1.39 (95% CI, 1.02–1.89). DBP and pre-frailty were not associated with falls after multivariate adjustment. SBP, DBP, and frailty status were not associated with severe falls after multivariate adjustment. Conclusions: SBP and frailty but not DBP and pre-frailty are associated with increased odds of falls among Chinese community-dwelling oldest olds.

IntroductionCOVID-19 deaths are commoner among care-home residents, but the mortality burden has not been quantified.MethodsCare-home residency was identified via a national primary care registration database linked to national mortality data. Life expectancy was estimated using Makeham-Gompertz models, to (i) describe yearly life expectancy from Nov 2015 to Oct 2020 (ii) compare life expectancy (during 2016-2018) between care-home residents and the wider Scottish population and (iii) apply care-home life expectancy estimates to COVID-19 death counts to estimate years of life lost (YLL).ResultsAmong care-home residents, life expectancy in 2015/16 to 2019/20 ranged from 2.7 to 2.3 years for women and 2.3 to 1.8 years for men. Life expectancy was lowest in 2019/20. Age-sex specific life expectancy in 2016-2018 in care-home residents was lower than in the Scottish population (10 and 2.5 years in those aged 70 and 90 respectively). Rather than using national life tables, applying care-home specific life expectancies to COVID-19 deaths yields, mean YLLs for care-home residents were 2.6 and 2.2 for women and men respectively, with total care-home resident YLLs of 3,560 years in women and 2,046 years in men. In people aged over-70, approximately half of deaths and a quarter of YLL attributed to COVID-19 were accounted for by the 5% of over-70s who were care-home residents.ConclusionPrioritising care-home residents for vaccination is justified not only in terms of total deaths, but also in terms of years of life lost.Research in contextEvidence before this studyWe searched PubMed to 1st December 2020, with the terms (“nursing home” OR “care-home” OR “long-term care” OR “residential care”) AND (“mortality” OR “life expectancy” OR “length of stay”). We also searched for studies specific to the impact of the COVID-19 pandemic on those living in care-homes. We restricted our search to publications in English. Usual care-home life expectancy, in a UK context, has not previously been defined. One systematic review of length of stay was identified, which found significant heterogeneity in factors and associations. The impact of COVID-19 on excess mortality among care-home residents was noted, but the impact on life expectancy was not reported. Studies evaluating life expectancy among older people in the COVID-19 pandemic have not taken account of residency in their estimates.Added value of this studyUsing Scottish national representative linked data we describe the usual life expectancy of older adults (aged ≥70 years) living in care-homes, compared to older people living elsewhere. Deaths among care-home residents account for a considerable proportion of all mortality in older adults, around 19% for men and 30% for women. Life expectancy in care-home residents during the pandemic fell by almost 6 months, from 2.7 to 2.3 years in men and 2.1 to 1.8 years in women. In total, over 5,600 Years of Life were Lost (YLL) by care-home residents in Scotland who died with COVID-19. Around half of COVID-19 deaths and a quarter of YLL in those aged 70 years and over occurred among care-home residents. During the COVID-19 pandemic a smaller proportion of deaths among care-home residents occurred in hospitals.Implications of all the available evidencePrioritising the 5% of older adults who are care-home residents for vaccination against COVID-19 is justified both in terms of total deaths and total years of life lost. Individual and societal planning for care needs in older age relies on understanding usual care-home life expectancy and patterns of mortality. Understanding life expectancy may help clinicians, residents and their families make decisions about their health care, facilitating more informed discussions around their priorities and wishes. Population-wide estimates of YLL and burden of disease should take account of residency status, given the significant differences between life expectancy of those living in care-homes from their peers in other settings.

Features of the deaths caused by COPD (chronic obstructive pulmonary disease) in cancer patients remained a controversial issue. This study aimed to characterize the demographic characteristics and mortality rates of the deaths from COPD in patients with cancer. In total, 7,846,370 cancer patients aged 40 years or older in the United States were identified from the Surveillance, Epidemiology, and End Results database (1975-2016). Mortality rates and SMRs (standardized mortality ratios) adjusted by age, race, sex, and calendar year were calculated to investigate the risk of COPD deaths in cancer survivors and to compare it with the general population. A total of 119,228 COPD deaths in patients with cancer were recorded, with a mortality rate of 261.5/100,000 person-years, nearly two-fold that of the general population (SMR, 2.17; 95% CI [confidence interval], 2.16-2.18). The proportion of cancer survivors dying from COPD increased from 0.9% in 1975 to 3.4% in 2016. Patients with lung cancer had a higher overall risk (SMR, 9.23; 95% CI, 9.12-9.35) than those with extrapulmonary malignancies. Among all extrapulmonary sites, laryngeal (SMR, 5.54; 95% CI, 5.34-5.75) and esophageal cancers (SMR, 4.33; 95% CI, 4.04-4.63) had the highest SMR. The risk of death from COPD increased with follow-up time.

The year 2021 marks the 50th anniversary of the National Cancer Act of 1971 and President Richard Nixon's declaration of a "war on cancer". In 1971 cancer was the second leading cause of death in the USA, and today it is still the second leading cause of death with an estimated 606,520 Americans dying of cancer in the year 2020. The half a century campaign to eliminate cancer reveals at least two important public health lessons that must be heeded for the next 50 years of the war against the disease-(1) recognizing the limits of behaviour control and (2) recognizing the significance of rate (of ageing) control. These two lessons result in a somewhat paradoxical conclusion in that we must have both humility and ambition in our attitudes towards future preventative medicine for the world's ageing populations. Geroscience must become an integral part of public health if serious headway is to be made preventing not only cancer but most of the other chronic conditions of late life.

Uric acid is both a pro-oxidant and antioxidant. We investigated serum uric acid's association with mortality and aging biomarkers in older adults with varying levels of grip strength. A total of 5329 community-dwelling adults aged ≥55 years underwent assessments of serum uric acid levels, grip strength, and biomarkers of diverse physiological systems. The primary outcome was all-cause mortality. We observed a significant (P < .001) interaction between uric acid levels and grip strength on all-cause mortality risk. Among participants with low grip strength, a nonlinear association (P for nonlinearity = .006) was observed between serum uric acid levels and mortality risk after multivariate adjustment. Compared with participants with neither extreme uric acid levels nor low grip strength, those with a combination of high serum uric acid and low grip strength exhibited greater risks of mortality (adjusted hazard ratio [aHR], 1.52; 95% confidence interval [CI], 1.15–2.02) and deviations in biomarkers of specific systems, so did those with a combination of low serum uric acid and low grip strength (aHR, 1.52; 95% CI, 1.13–2.05). In conclusion, there was a J-shaped association between serum uric acid and the risk of all-cause mortality in older adults. This was primarily true for those with low grip strength.

With age-related functional deterioration, sensory impairment including vision impairment (VI), hearing impairment (HI), and dual sensory impairment (DSI) usually occurred among the elderly population, causing a decrease in functional capacity and quality of life. The study aimed to explore how sensory impairment is associated with the risk of all-cause mortality among the elderly adults in China. We prospectively investigated the association among 37,076 participants enrolled from 1998 to 2019 in the Chinese Longitudinal Healthy Longevity Survey. We also, as a sensitivity analysis, explored the association among 11,365 newly incident sensory impairment participants. Cox regression model with sensory impairment as a time-varying exposure was performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Compared with participants without sensory impairment, those with VI (HR=1.20, 95% CI: 1.15-1.24), HI (HR=1.26, 95% CI: 1.21-1.31), and DSI (HR: 1.46, 95% CI=1.41-1.52) had significant higher risk of all-cause mortality after adjusting for potential confounders. These associations were robust among subgroup analyses stratified by sex and entry age, and sensitivity analyses performed among newly incident sensory impairment participants. In conclusion, sensory impairment was associated with higher mortality risk among the elderly adults in China.

Aims During the COVID-19 pandemic, hospital admissions for cardiac care have declined. However, effects on mortality are unclear. Thus, we sought to evaluate the impact of the lockdown period in central Germany on overall and cardiovascular deaths. Simultaneously we looked at catheterization activities in the same region. Methods and results Data from 22 of 24 public health-authorities in central Germany were aggregated during the pandemic related lockdown period and compared to the same time period in 2019. Information on the total number of deaths and causes of death, including cardiovascular mortality, were collected. Additionally, we compared rates of hospitalization (n = 5178) for chronic coronary syndrome (CCS), acute coronary syndrome (ACS), and out of hospital cardiac arrest (OHCA) in 26 hospitals in this area. Data on 5,984 deaths occurring between March 23, 2020 and April 26, 2020 were evaluated. In comparison to the reference non-pandemic period in 2019 (deaths: n = 5832), there was a non-significant increase in all-cause mortality of 2.6% [incidence rate ratio (IRR) 1.03, 95% confidence interval (CI) 0.99–1.06; p = 0.16]. Cardiovascular and cardiac mortality increased significantly by 7.6% (IRR 1.08, 95%-CI 1.01–1.14; p = 0.02) and by 11.8% (IRR 1.12, 95%-CI 1.05–1.19; p Conclusion During the COVID-19-related lockdown a significant increase in cardiovascular mortality was observed in central Germany, whereas catherization activities were reduced. The mechanisms underlying both of these observations should be investigated further in order to better understand the effects of a pandemic-related lockdown and social-distancing restrictions on cardiovascular care and mortality. Graphic abstract

Introduction Tobacco use is a leading cause of death and disability worldwide, particularly in South-East Asia. The tobacco problem in India is probably more complex than in any other country, with a huge consequential burden of tobacco related diseases and deaths. The present study aimed at analyzing the pattern and predictors of tobacco use among college students aged 18-24 years, using the Global Tobacco Surveillance System (GTSS). Methods A cross-sectional study was conducted among 2063 students, from 30 colleges of Mangalore, South India, who were selected by multistage sampling with probability proportional to size. The tobacco questions used for this study were a validated, recommended subset of key questions from the Global Adult Tobacco Survey (GATS). Data analysis was performed using GATS manuals and SPSS version 24.0. Results A total of 2063 students participated in the study (738 males, 1325 females). Prevalence of tobacco smoking was 4.8%, which included 9.9% males and 2.1% females. Manufactured cigarettes were the most commonly preferred tobacco product among daily smokers. The overall percentage of smokeless tobacco use was 4.8%, which included 7.4% males and 3.3% females. Logistic regression analysis showed that 71.4% of the participants who noticed anticigarette information on television made an attempt to quit smoking. The odds ratio (OR) of quitting was 4.4 times higher compared to those who did not notice any information on television (p=0.002). In addition, noticing health warnings on cigarette packs strongly influenced an individual to quit smoking (OR=30.09). Conclusions The study results showed low prevalence of the use of both smoked and smokeless forms of tobacco, current smoking, and chewing tobacco, among the study population. Generating data in this part of the country on tobacco use and developing tobacco control measures at regular intervals are essential to better understand and develop effective intervention programs.

Objectives We aimed to investigate long-term survival of paclitaxel DCB for percutaneous coronary intervention (PCI). Background Safety concerns have been raised over the use of paclitaxel devices for peripheral artery disease recently, following a meta-analysis suggesting increased late mortality. With regard to drug-coated balloon (DCB) angioplasty for coronary artery intervention however, there is limited data to date regarding possible late mortality relating to paclitaxel. Methods We compared all-cause mortality of patients treated with paclitaxel DCB to those with non-paclitaxel second-generation drug-eluting stents (DES) for stable, de novo coronary artery disease from 1st January 2011 till 31st December 2018. To have homogenous groups allowing data on safety to be interpreted accurately, we excluded patients with previous PCI and patients treated with a combination of both DCB and DES in subsequent PCIs. Data were analysed with Kaplan–Meier curves and Cox regression statistical models. Results We present 1517 patients; 429 treated with paclitaxel DCB and 1088 treated with DES. On univariate analysis, age, hypercholesterolaemia, hypertension, peripheral vascular disease, prior myocardial infarction, heart failure, smoking, atrial fibrillation, decreasing estimated glomerular filtration rate (eGFR) [and renal failure (eGFR p = 0.08). On multivariable analysis age, decreasing eGFR and smoking associated with worse prognosis. Conclusion We found no evidence of late mortality associated with DCB angioplasty compared with non-paclitaxel second-generation DES in up to 5 years follow-up. DCB is a safe option for the treatment of de novo coronary artery disease.

Cardiovascular diseases (CVD) are the world's leading cause of death. High blood pressure (BP) is the leading global risk factor for all‐cause preventable morbidity and mortality. Globally, only about 14% of patients achieve BP control to systolic BP 60%) require two or more drugs to achieve BP control, yet poor adherence to therapy is a major barrier to achieving this control. Fixed‐dose combinations (FDCs) of BP‐lowering drugs are one means to improve BP control through greater adherence and efficacy, with favorable safety and cost profiles. The authors present a review of the supporting data from a successful application to the World Health Organization (WHO) for the inclusion of FDCs of two BP‐lowering drugs on the 21st WHO Essential Medicines List. The authors discuss the efficacy and safety of FDCs of two BP‐lowering drugs for the management of hypertension in adults, relevant hypertension guideline recommendations, and the estimated cost of such therapies.

DNA methylation has fundamental roles in gene programming and aging that may help predict mortality. However, no large-scale study has investigated whether site-specific DNA methylation predicts all-cause mortality. We used the Illumina-HumanMethylation450-BeadChip to identify blood DNA methylation sites associated with all-cause mortality for 12, 300 participants in 12 Cohorts of the Heart and Aging Research in Genetic Epidemiology (CHARGE) Consortium. Over an average 10-year follow-up, there were 2,561 deaths across the cohorts. Nine sites mapping to three intergenic and six gene-specific regions were associated with mortality (P < 9.3x10-7) independently of age and other mortality predictors. Six sites (cg14866069, cg23666362, cg20045320, cg07839457, cg07677157, cg09615688)—mapping respectively to BMPR1B, MIR1973, IFITM3, NLRC5, and two intergenic regions—were associated with reduced mortality risk. The remaining three sites (cg17086398, cg12619262, cg18424841)—mapping respectively to SERINC2, CHST12, and an intergenic region—were associated with increased mortality risk. DNA methylation at each site predicted 5%¬¬–15% of all deaths. We also assessed the causal association of those sites to age-related chronic diseases by using Mendelian randomization, identifying weak causal relationship between cg18424841 and cg09615688 with coronary heart disease. Of the nine sites, three (cg20045320, cg07839457, cg07677157) were associated with lower incidence of heart disease risk and two (cg20045320, cg07839457) with smoking and inflammation in prior CHARGE analyses. Methylation of cg20045320, cg07839457, and cg17086398 was associated with decreased expression of nearby genes (IFITM3, IRF, NLRC5, MT1, MT2, MARCKSL1) linked to immune responses and cardiometabolic diseases. These sites may serve as useful clinical tools for mortality risk assessment and preventative care.

Background Environmental noise exposure has been associated with increased cardiovascular morbidity and mortality. Recently, noise annoyance was shown to induce atrial fibrillation, which was accompanied by significantly increased levels of midregional pro atrial natriuretic peptide (MR-proANP). Therefore, the aim of the present study was to analyze the association between noise annoyance, MR-proANP, incident cardiovascular events, and all-cause mortality. Methods Levels of MR-proANP were measured in the first 5000 participants of the population-based Gutenberg Health Study. Annoyance was assessed separately for aircraft, road traffic, railway, neighborhood, and industrial/construction noise during the day and sleep. Results In cross-sectional analyses, aircraft noise annoyance during day and sleep, industrial/construction noise annoyance during day, and railway noise annoyance during sleep were independently associated with increased levels of MR-proANP after multivariable adjustment. After a 5-year follow-up period, there were 43 cases of incident atrial fibrillation and 103 of incident cardiovascular disease (comprising atrial fibrillation, coronary artery disease, myocardial infarction, heart failure, or stroke). Moreover, there were 301 deaths after a mean follow-up of 7.42 ± 1.66 years. An odds ratio (OR) of 2.82 ([95% confidence interval (CI) 1.86; 4.35], p p = 0.0046) for incident cardiovascular disease per 1-standard deviation (SD) increase in MR-proANP levels were found. A 36% (hazard ratio: 1.36 [95% CI 1.19; 1.55], p Conclusions Noise annoyance may contribute to cardiovascular morbidity and mortality and is characterized by increased levels of MR-proANP. Graphic abstract

Atherosclerotic lesions in the great arteries are frequent findings in the elderly. Numerous studies have shown their strong predictive value for cardiovascular disease, embolic events, and mortality. We sought to determine the risk of all-cause mortality depending on the localization of plaques in the thoracic aorta evaluated by transesophageal echocardiography (TEE). A total of 2,054 patients (median age 65 years, interquartile range 52–73; 58% men) who underwent a TEE examination between 01/2007 and 03/2015 were retrospectively analyzed. For each patient, the presence of atherosclerotic lesions in the ascending aorta, the aortic arch, and in the descending aorta, as well as cardiovascular risk factors and survival were documented. Median follow-up period was 48 months (interquartile range 38–58). Multivariate Cox regression analysis indicated plaque in the ascending aorta (HR of 1.36, 95% CI 1.01–1.83, P = 0.046), the aortic arch (HR of 1.78, 95% CI 1.29–2.45, P

Background Iron deficiency is now accepted as an independent entity beyond anemia. Recently, a new functional definition of iron deficiency was proposed and proved strong efficacy in randomized cardiovascular clinical trials of intravenous iron supplementation. Here, we characterize the impact of iron deficiency on all-cause mortality in the non-anemic general population based on two distinct definitions. Methods The Gutenberg Health Study is a population-based, prospective, single-center cohort study. The 5000 individuals between 35 and 74 years underwent baseline and a planned follow-up visit at year 5. Tested definitions of iron deficiency were (1) functional iron deficiency—ferritin levels below 100 µg/l, or ferritin levels between 100 and 299 µg/l and transferrin saturation below 20%, and (2) absolute iron deficiency—ferritin below 30 µg/l. Results At baseline, a total of 54.5% of participants showed functional iron deficiency at a mean hemoglobin of 14.3 g/dl; while, the rate of absolute iron deficiency was 11.8%, at a mean hemoglobin level of 13.4 g/dl. At year 5, proportion of newly diagnosed subjects was 18.5% and 4.8%, respectively. Rate of all-cause mortality was 7.2% (n = 361); while, median follow-up was 10.1 years. After adjustment for hemoglobin and major cardiovascular risk factors, the hazard ratio with 95% confidence interval of the association of iron deficiency with mortality was 1.3 (1.0–1.6; p = 0.023) for the functional definition, and 1.9 (1.3–2.8; p = 0.002) for absolute iron deficiency. Conclusions Iron deficiency is very common in the apparently healthy general population and independently associated with all-cause mortality in the mid to long term. Graphic abstract

Background: Patients with chronic kidney disease (CKD) are associated with high prevalence rates of proteinuria, vascular calcification and cardiomegaly. In this study, we investigated relationships among proteinuria, aortic arch calcification (AoAC) and cardio-thoracic ratio (CTR) in patients with CKD stage 3A-5. In addition, we investigated correlations among proteinuria and decline in renal function, overall and cardiovascular (CV) mortality. Methods: We enrolled 482 pre-dialysis patients with CKD stage 3A-5, and determined AoAC and CTR using chest radiography at enrollment. The patients were stratified into four groups according to quartiles of urine protein-to-creatinine ratio (UPCR). Results: The patients in quartile 4 had a lower estimated glomerular filtration rate (eGFR) slope, and higher prevalence rates of rapid renal progression, progression to commencement of dialysis, overall and CV mortality. Multivariable analysis showed that a high UPCR was associated with high AoAC (unstandardized coefficient β: 0.315; p = 0.002), high CTR (unstandardized coefficient β: 1.186; p = 0.028) and larger negative eGFR slope (unstandardized coefficient β: -2.398; p < 0.001). With regards to clinical outcomes, a high UPCR was significantly correlated with progression to dialysis (log per 1 mg/g; hazard ratio [HR], 2.538; p = 0.003), increased overall mortality (log per 1 mg/g; HR, 2.292; p = 0.003) and increased CV mortality (log per 1 mg/g; HR, 3.195; p = 0.006). Conclusions: Assessing proteinuria may allow for the early identification of high-risk patients and initiate interventions to prevent vascular calcification, cardiomegaly, and poor clinical outcomes.

Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China. The clinical data in other centers is limited. This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19). Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group. Clinical information was collected and analyzed for the following objectives: 1. Comparisons of basic characteristics between two groups; 2. Risk factors for death on admission using logistic regression; 3. Dynamic changes of radiographic and laboratory parameters between two groups in the course. Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89). Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression. Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p77.35mg/L, PCT>0.20μg/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p

Background Mid‐regional pro‐atrial natriuretic peptide (MR‐proANP) is a strong prognostic marker in several inflammatory, respiratory and cardiovascular conditions, but has not been studied in COVID‐19 yet. Methods This prospective, observational study of patients with COVID‐19 infection was conducted from 6 June to 26 November 2020 in different wards of a tertiary hospital. MR‐proANP, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and high‐sensitive cardiac troponin I levels on admission were collected and tested for their association with disease severity and 28‐day mortality. Results A total of 213 eligible patients with COVID‐19 were included in the final analyses of whom 13.2% (n = 28) died within 28 days. Median levels of MR‐proANP at admission were significantly higher in nonsurvivors (307 pmol/L IQR, [161 ‐ 532] vs 75 pmol/L [IQR, 43 ‐ 153], P

Community-acquired pneumonia (CAP) is a lower respiratory tract infection. It is one of the commonest infectious diseases and the third leading cause of death worldwide. However, the epidemiological profiles of CAP in southeastern China are unknown. Data of inpatients and outpatients diagnosed with CAP from January 1, 2015 to December 31, 2020 were obtained from the National Healthcare Big Data in Fuzhou (Fuzhou Database). This database covers medical data from 37 hospitals and 159 community health service stations. The incidence rate, treatment pattern, and direct medical costs of CAP were assessed using clinical data. A total of 8,156,237 patients were enrolled, with a mean age of 33.72 ± 20.88 years. The overall incidence rate of CAP was 3.13 (95% confidence interval [CI]: 3.11–3.15) per 1000 person-years (PY), with 15.97 (95% CI: 15.85–16.08) per 1000 PY in children below 5 years old and 2.62 (95% CI: 2.57–2.66) per 1000 PY in the elderly ≥60 years. The cost per outpatient was $242.83 ± 341.62, and the cost per inpatient was $4,530.4 ± 9,151.68. The three most used therapeutic drugs in patients with CAP are cefotaxime, moxifloxacin, and azithromycin. In addition, despite the ability of both imported and domestic pneumococcal conjugate vaccines to reduce the incidence rate of CAP, the current vaccination coverage rates were relatively low. We suggest that more attention should be paid to the disease burden of CAP, especially due to its great economic burden in China.

Background: We aimed to evaluate atrial fibrillation occurrence, reasons for healthcare visits, mortality, causes of death and examined patterns by relative deprivation in the UK. Methods: To study the atrial fibrillation (AF) incidence, mortality and case-fatality, we implemented a prospective cohort study with the linked electronic health records of 5.6 million population in the United Kingdom Clinical Practice Research Datalink from 1998 to 2016. A matched case-control study was used to investigate causes of hospitalisation and death comparing individuals with and without incident AF. Results: During a median follow-up of 10.3 years, 199,433(3.6%) patients developed incident AF. Increased risk of hospitalisation for heart failure, cardiovascular conditions and infection was present among patients who later developed AF. Following an AF diagnosis, patients were frequently admitted to the hospital for heart failure, lower respiratory tract infection, chronic obstructive pulmonary disease and ischemic heart disease. One in 5 AF patients died during the first year after diagnosis, and the mortality increased to 42.7% at the fifth year. The excess deaths in AF cases compared to controls may result from cardiovascular diseases, infection and metabolic disorders. Individuals from areas with higher deprivation in socioeconomic and living status had both higher AF incidence and fatality. Interpretation: We observed an elevated risk of hospitalisation for cardiovascular or respiratory diseases among incident AF patients, and the considerable disparity in AF burden by socioeconomic deprivation informs priorities for prevention and provision of patient care. Funding: The study was supported by the GlaxoSmithKline, University College London Hospital and National Institute for Health Research. The funders did not have any role in study design, data collection, data analysis, interpretation, and writing of the report.

The World Health Organization (WHO) has published a guideline for the management of individuals with advanced HIV disease (AHD) to reduce HIV-related deaths. The guideline consists of a package of recommendations including interventions to prevent, diagnose and treat common opportunistic infections, including tuberculosis (TB), cryptococcosis and severe bacterial infections, along with rapid initiation of antiretroviral treatment and enhanced adherence support. Currently no clear targets exist for these key interventions. Emerging programmatic data from Uganda, Tanzania and Nigeria suggest that an estimated 80% of eligible people continue to miss the recommended cryptococcal or TB testing, highlighting the remaining challenges to the effective implementation of WHO-recommended AHD packages of care in real-world resource-limited settings. The absence of mortality indicators for the leading causes of HIV-related deaths, because of the lack of mechanisms to ascertain cause of death, has had a negative impact on establishing interventions to reduce mortality. We suggest that setting 95-95-95 targets for CD4 testing, cryptococcal antigen and TB testing, and treatment that are aligned to the WHO AHD package of care would be a step in the right direction to achieving the greater goal of the WHO End TB strategy and the proposed new strategy to end cryptococcal meningitis deaths. However, these targets will only be achieved if there is healthcare worker training, expanded access to bedside point-of-care diagnostics for hospitalised patients and those in outpatient care who meet the criteria for AHD, and health systems strengthening to minimise delays in initiating the WHO-recommended therapies for TB and cryptococcal disease.

Background Unintentional injury is a leading cause of death/disability, with more disadvantaged children at greater risk. Understanding how inequalities vary by injury type, age, severity, and place of injury, can inform prevention. Methods For all Scotland-born children 2009-2013 (n=195,184), hospital admissions for unintentional injury (HAUI) were linked to socioeconomic circumstances (SECs) at birth: area deprivation via the Scottish Index of Multiple Deprivation (SIMD), mother's occupational social class, parents’ relationship status. HAUI was examined from birth-five, and during infancy. We examined HAUI frequency, severity, injury type, and injury location (home vs. elsewhere). We estimated relative inequalities using the relative indices of inequality (RII, 95% CIs), before and after adjusting for demographics and other non-mediating SECs. Findings More disadvantaged children were at greater risk of any HAUI from birth-five, RII: 1•59(1•49-1•70), 1•74(1•62-1•86), 1•97(1•84-2•12) for area deprivation, maternal occupational social class, and relationship status respectively. These attenuated after adjustment (1•15 [1•06-1•24], 1.22 [1•12-1•33], 1.32 [1•21-1•44]). Inequalities were greater for severe (vs. non-severe), multiple (vs. one-off) and home (vs. other location) injuries. Similar patterns were seen in infancy, excluding SIMD-inequalities in falls, where infants living in more disadvantaged neighbourhoods were at lower risk (0•79 [0•62-1•00]). After adjustment, reverse SIMD-gradients were also observed for all injuries and poisonings. Interpretation Children living in more disadvantaged households are more likely to be injured across multiple dimensions of HAUI in Scotland. Upstream interventions which tackle family-level disadvantage may be most effective at reducing childhood HAUI. Funding Wellcome Trust, Medical Research Council, Scottish Government Chief Scientist Office.

Background Suicide is a major public health problem, with far-reaching social, emotional and economic consequences. Suicide rates are high in all age groups are particularly high in all age groups but are one of the major causes of death among younger age groups, yeilding substantial years of premature life lost. Preventing suicide is one of the major mental health challenges in the world. Objective The aim of this study was to estimate the number and rates of suicide deaths in the Federation of Bosnia and Herzegovina (FB&H), and describe suicide characteristics by sex, age, method of suicide over the period of 2010 to 2020. Methods This is a retrospective population-based study from the period 2010 - 2020. Data were from the FB&H mortality register, Institute for Statistics FB&H. Data on deaths by cause of death are given according to the 10th edition of the International Statistical Classification of Diseases, Injuries and Causes of Death. Suicide data were presented rates by three age group, total number, male and female, crude rates, age-specific death rates and suicide mechanism by age and gender. Results The total number of suicides increased until 2017 to a peak of 201, then decreased to 157 for 2020. Males comprised over 70% of the suicide deaths. Over half of suicides were among those aged 30 - 64 and nearly one third among those 65 and above. However, the greatest increases were among youth aged 15 to 29, which grew from 2% to 9% of suicides over teh study period. The most common mechanisms for suicide were for hanging and firearms, both most common amond males. Poisoning was the most common mechanism among females. Conclusion Understanding age and mechanism trends over time will help prioritize prevention strategies. Focus on mental health systems needs to ensure equal access to high-quality services in community based settings. For responses to this challenge to be effective, a comprehensive multisectoral suicide prevention strategy is needed.

The prevalence of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is increasing day by day in the region, including Turkey. The study aimed to examine AIDS-related deaths in Turkey between 2009 and 2018 according to the national death registration system records. In this descriptive study, data on AIDS-related deaths were obtained from the Turkish Statistical Institute. The data consist of the cause of death codes, year of death, age and gender. Findings were presented using numbers and percentages. Seven hundred twenty-one AIDS-related deaths were reported in Turkey between 2009 and 2018. AIDS-related deaths in Turkey increased more than twice at the end of 10 years. The male/female death ratio is 4.5. Deaths under the age of 15 were 4.2% in total; however, they were increased to 10.2% in 2018. AIDS-related deaths are decreasing in the world but increasing in Turkey. The data from the Ministry of Health do not match the data of the national death registration system. Establishing a strong and accurate HIV/AIDS reporting system and identifying the causes and risk groups of this increase in AIDS-related deaths are critical.

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

As obesity becomes more common worldwide, the prevalence of obstructive sleep apnoea (OSA) continues to rise. Obstructive sleep apnoea is a well-known disorder that causes chronic intermittent hypoxia (CIH), which is considered a risk factor for atherosclerosis directly and indirectly. Ischaemic heart disease remains the leading cause of death. Most risk factors for atherosclerosis are well understood. However, other factors such as CIH are less well understood. Several studies have investigated the pathophysiology of CIH, attempting to uncover its link to atherosclerosis and to determine whether OSA treatment can be a therapeutic modality to modify the risk for atherosclerosis. In this article, we will review the pathophysiology of OSA as an independent risk factor for cardiovascular disease and discuss the most common markers that have been studied. We will also examine the potential impact of OSA management as a risk factor modifier on the reversibility of atherosclerosis.

Background: Recent progress in the diagnosis and treatment of primary and metastatic cutaneous melanoma (CM) has led to a significant increase in the patients` expectancy of life. The development of additional primary tumors (APT) other than CM represents an important survival issue. Results: Of a total of 1764 CM patients, 80 (4.5%) patients developed APT. For tumors diagnosed after CM, there was a 2.7 fold excess risk for APT compared to the swiss german population. A significantly increased risk was noted for female breast (SIR, 2.46), male larynx (SIR, 76.92), male multiple myeloma (SIR, 11.2), male oesophagus (SIR, 10.8) and thyroid on males (SIR, 58.8) and females (SIR, 38.1). All thyroid cancer cases had a common papillary histological subtype and a high rate of BRAFV600E mutation. Melanoma was the primary cause of death in the vast majority of patients. Methods: We used the cancer registry from the Comprehensive Cancer Center Zurich (CCCZ) and retrospectively analyzed patients with CM and APT between 2008 and 2018. We calculated the risk of APT compared to the swiss german population using the standardized incidence ratio (SIR). Conclusions: Patients with CM have an increased risk for hematologic and solid APT. Long-term follow-up is indicated.

Background: Acute myeloid leukemia (AML) is a common hematological malignancy treated with regimens containing anthracycline, an agent with cardiotoxicity. However, the cardiac-specific mortality in AML patients receiving chemotherapy remains unknown. Methods: In this population-based study, patients diagnosed with AML between 1973 and 2015 were identified in the Surveillance, Epidemiology, and End Results database. Cumulative mortality by cause of death was calculated. To quantify the excessive cardiac-specific death compared with the general population, standardized mortality ratios (SMRs) were calculated. Multivariate Cox regression analyses were performed to identify risk factors associated with cardiac-specific death and AML-specific death. Results: A total of 64,679 AML patients were identified between 1973 and 2015; 68.48% of patients (44,292) received chemotherapy. Among all possible competing causes of death, AML was associated with the highest cumulative mortality. The AML patients who received chemotherapy showed excessive cardiac-specific mortality compared with the general population, with an SMR of 6.35 (95% CI: 5.89-6.82). Age, year of diagnosis, sex, and marital status were independently associated with patient prognosis. Conclusion: Cardiac-specific mortality in AML patients receiving chemotherapy is higher than that in the general population.

ObjectiveTo assess trends of mortality attributable to child and maternal undernutrition (CMU), overweight/obesity and dietary risks of non-communicable diseases (NCD) in sub-Saharan Africa (SSA) using data from the Global Burden of Disease (GBD) Study 2015.DesignFor each risk factor, a systematic review of data was used to compute the exposure level and the effect size. A Bayesian hierarchical meta-regression analysis was used to estimate the exposure level of the risk factors by age, sex, geography and year. The burden of all-cause mortality attributable to CMU, fourteen dietary risk factors (eight diets, five nutrients and fibre intake) and overweight/obesity was estimated.SettingSub-Saharan Africa.ParticipantsAll age groups and both sexes.ResultsIn 2015, CMU, overweight/obesity and dietary risks of NCD accounted for 826204 (95 % uncertainty interval (UI) 737346, 923789), 266768 (95 % UI 189051, 353096) and 558578 (95 % UI 453433, 680197) deaths, respectively, representing 10·3 % (95 % UI 9·1, 11·6 %), 3·3 % (95 % UI 2·4, 4·4 %) and 7·0 % (95 % UI 5·8, 8·3 %) of all-cause mortality. While the age-standardized proportion of all-cause mortality accounted for by CMU decreased by 55·2 % between 1990 and 2015 in SSA, it increased by 63·3 and 17·2 % for overweight/obesity and dietary risks of NCD, respectively.ConclusionsThe increasing burden of diet- and obesity-related diseases and the reduction of mortality attributable to CMU indicate that SSA is undergoing a rapid nutritional transition. To tackle the impact in SSA, interventions and international development agendas should also target dietary risks associated with NCD and overweight/obesity.