Search

Sudden unexpected death of an individual with epilepsy can pose a challenge to death investigators, as most deaths are unwitnessed, and the individual is commonly found dead in bed. Anatomic findings (eg, tongue/lip bite) are commonly absent and of varying specificity, thereby limiting the evidence to implicate epilepsy as a cause of or contributor to death. Thus it is likely that death certificates significantly underrepresent the true number of deaths in which epilepsy was a factor. To address this, members of the National Association of Medical Examiners, North American SUDEP Registry, Epilepsy Foundation SUDEP Institute, American Epilepsy Society, and the Centers for Disease Control and Prevention constituted an expert panel to generate evidence-based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of autopsy and toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance of epilepsy-related deaths. The recommendations provided in this paper are intended to assist medical examiners, coroners, and death investigators when a sudden unexpected death in a person with epilepsy is encountered. [ABSTRACT FROM AUTHOR]

The ongoing COVID‐19 pandemic caused by SARS‐CoV‐2 has caused widespread deaths, illnesses, and societal disruption. I describe here how I pivoted a discussion‐based senior biology capstone course to include a multiweek module surrounding one primary literature paper on the evolution of SARS‐CoV‐2 and the subsequent scientific discourse about the paper. Using a gradual reveal of the paper following the CREATE method (consider, read, elucidate, and think of the next experiment), I challenged students to learn new evolutionary principles and critically analyze the data surrounding the evolution and transmission of SARS‐CoV‐2 presented in the paper. I also provide general advice for implementing this module in future courses. [ABSTRACT FROM AUTHOR]

Background: Liver disease is a growing health concern and a major cause of death. It causes multiple symptoms, including financial, psychological and social issues. To address these challenges, palliative care can support people alongside active treatment, and towards the end of life, but little is known about the care experiences of individuals with liver disease in the United Kingdom. This review aimed to explore the palliative and end‐of‐life care experiences of people with liver disease in the United Kingdom. Method: A systematic review was conducted using a five‐stage process and following Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. Searches were across Web of Science, Scopus, EBSCO and grey literature until 10 May 2023. The review was registered through International Prospective Register of Systematic Reviews (PROSPERO). NVivo 12.5 was used to facilitate data analysis (systematic review registration: PROSPERO CRD42022382649). Results: Of 6035 papers (excluding duplicates) found from searches, five met the inclusion criteria of primary research related to adults with liver disease receiving palliative and/or end‐of‐life care in the United Kingdom, published in English. Reflexive thematic analysis of the data was conducted. The themes identified were the experiences of people with liver disease of relating to healthcare professionals, using services, receiving support, and experiences of information and communication. These were connected by an overarching concept of disempowerment versus empowerment, with the notion of person‐centred care as an important feature. Conclusion: This review has found variations in the care experiences of people with advanced liver disease towards the end of life and an overall lack of access to specialist palliative care services. Where services are designed to be person‐centred, experiences are more empowering. Further research is needed but with recognition that it is often unclear when care for people with liver disease is palliative or end‐of‐life. Patient and Public Contribution: An online public involvement workshop was held on 18 April 2023 through Voice (2023). This included four people with liver disease and four carers to discuss the review findings and to design a qualitative research study to further explore the topic. [ABSTRACT FROM AUTHOR]

This article is an editor's introduction to the magazine. The article by Roland Kirstein and Stefan Voigt, "The Violent and the Weak: When Dictators Care about Social Contracts" is highlighted with the allegory of hens who need protection to lay their eggs, so they hire foxes to guard them. The other six articles use theories and formulas to show what is wrong with "conventional wisdom" when tackling economic and societal problems. The author also highlights the article from Richard J. Cebula and Tatyana V. Zelensaya "Determinants of Youth Suicide," in which they write about the commonly accepted ideas about suicide, and then expand on the definitions of these ideas.

This article presents global cancer statistics by world region for the year 2022 based on updated estimates from the International Agency for Research on Cancer (IARC). There were close to 20 million new cases of cancer in the year 2022 (including nonmelanoma skin cancers [NMSCs]) alongside 9.7 million deaths from cancer (including NMSC). The estimates suggest that approximately one in five men or women develop cancer in a lifetime, whereas around one in nine men and one in 12 women die from it. Lung cancer was the most frequently diagnosed cancer in 2022, responsible for almost 2.5 million new cases, or one in eight cancers worldwide (12.4% of all cancers globally), followed by cancers of the female breast (11.6%), colorectum (9.6%), prostate (7.3%), and stomach (4.9%). Lung cancer was also the leading cause of cancer death, with an estimated 1.8 million deaths (18.7%), followed by colorectal (9.3%), liver (7.8%), female breast (6.9%), and stomach (6.8%) cancers. Breast cancer and lung cancer were the most frequent cancers in women and men, respectively (both cases and deaths). Incidence rates (including NMSC) varied from four‐fold to five‐fold across world regions, from over 500 in Australia/New Zealand (507.9 per 100,000) to under 100 in Western Africa (97.1 per 100,000) among men, and from over 400 in Australia/New Zealand (410.5 per 100,000) to close to 100 in South‐Central Asia (103.3 per 100,000) among women. The authors examine the geographic variability across 20 world regions for the 10 leading cancer types, discussing recent trends, the underlying determinants, and the prospects for global cancer prevention and control. With demographics‐based predictions indicating that the number of new cases of cancer will reach 35 million by 2050, investments in prevention, including the targeting of key risk factors for cancer (including smoking, overweight and obesity, and infection), could avert millions of future cancer diagnoses and save many lives worldwide, bringing huge economic as well as societal dividends to countries over the forthcoming decades. [ABSTRACT FROM AUTHOR]

EDITOR-The commentary on our paper[[1]] prompted us to further explore our data on coding cerebral palsy (CP) as the underlying cause of death. This number remained the same regardless of revising the cause of death where the underlying cause of death was coded as CP. [Extracted from the article]

Background: The neurovascular unit (NVU) is emerging as a potential therapeutic target in neurological conditions, such as stroke, brain injury, Alzheimer's disease, and Parkinson's disease; meanwhile, stroke is the second leading cause of death globally. The purpose of the study is to analyze the most influential articles, authors, countries, and topics in the role of NVU in stroke. Methods: The Web of Science (WoS) database was used for bibliometric analysis using the search terms "Stroke" and "Neurovascular unit" on January 1st, 2021. Data were extracted from the WoS database to identify collaborations between authors, countries, organizations, and keywords using VOSviewer (1.6.16 mac). Two bibliometric indicators, the activity index (AI) and category normalized citation impact (CNCI), were computed. The keywords of bursts were also identified by CiteSpace. Results: A total of 770 articles were analyzed by VOSviewer. AIs and CNCIs were computed of the eighteen countries according to VOSviewer co‐authorship analysis results. The majority of authors mainly came from the United States and Japan. Romania, Hungary, and Poland have emerged as rising‐star countries. In the 100 most‐cited articles, the number of citations ranged from 1873 to 69, with a total of 15,758 citations. Most articles were published in 2011 and 2012 (n = 13 each), followed by 2009 (n = 11) and 2013, 2014, and 2015 (n = 8 each). Stroke and Journal of Cerebral Blood Flow and Metabolism were the two top journals. EH Lo from Harvard University/ Massachusetts General Hospital was the top first author and corresponding author. Harvard University/Massachusetts General Hospital was the most productive affiliated institution with 15 publications. Conclusion: There has been growing attention and efforts made in the field of stroke and NVU. The merit of the above findings may help to shape the research policy in ischemic stroke both at the country and institutional level. [ABSTRACT FROM AUTHOR]

The article explores the relationship with data from a nation with a substantially different social context, Japan. American research on suicide has been based largely on American samples. Little is known about whether the results of this work, such as the link between divorce and suicide, will be replicated for nations with substantially different institutional and cultural structures. The present paper tests the marital integration theory of suicide with data from Japan. Briefly, the marital integration theory holds that as bonds to marriage weaken, suicide risk increases. Further, the kinship system in Japan is apparently more integrated than it is in the United States. For example, in Japan 37.3% of the elderly lived in three-generation households compared to only 0.5% of the elderly in the United States. Durkheim's theory of social integration and suicide emphasizes the subordination of the individual to group life as a prophylactic against suicide. Individualism in family life was emerging as the pattern for the future at the time of Durkheim's study. It is anticipated that a rising divorce rate should affect suicide risk for several groups: divorced persons; separated persons who are contemplating divorce; married persons with severe marital problems; and the children in such families.

With the changing disease spectrum, atherosclerosis has become increasingly prevalent worldwide and the associated diseases have emerged as the leading cause of death. Due to their fascinating physical, chemical, and biological characteristics, nanomaterials are regarded as a promising tool to tackle enormous challenges in medicine. The emerging discipline of nanomedicine has filled a huge application gap in the atherosclerotic field, ushering a new generation of diagnosis and treatment strategies. Herein, based on the essential pathogenic contributors of atherogenesis, as well as the distinct composition/structural characteristics, synthesis strategies, and surface design of nanoplatforms, the three major application branches (nanodiagnosis, nanotherapy, and nanotheranostic) of nanomedicine in atherosclerosis are elaborated. Then, state‐of‐art studies containing a sequence of representative and significant achievements are summarized in detail with an emphasis on the intrinsic interaction/relationship between nanomedicines and atherosclerosis. Particularly, attention is paid to the biosafety of nanomedicines, which aims to pave the way for future clinical translation of this burgeoning field. Finally, this comprehensive review is concluded by proposing unresolved key scientific issues and sharing the vision and expectation for the future, fully elucidating the closed loop from atherogenesis to the application paradigm of nanomedicines for advancing the early achievement of clinical applications. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) significantly impacts global society since it is the leading cause of death and disability worldwide, and extracellular vesicle (EV)‐based therapies have been extensively investigated. EV delivery is involved in mediating the progression of CVDs and has great potential to be biomarker and therapeutic molecular carrier. Besides, EVs from stem cells and cardiac cells can effectively protect the heart from various pathologic conditions, and then serve as an alternative treatment for CVDs. Moreover, the research of using EVs as delivery carriers of therapeutic molecules, membrane engineering modification of EVs, or combining EVs with biomaterials further improves the application potential of EVs in clinical treatment. However, currently there are only a few articles summarizing the application of EVs in CVDs. This review provides an overview of the role of EVs in the pathogenesis and diagnosis of CVDs. It also focuses on how EVs promote the repair of myocardial injury and therapeutic methods of CVDs. In conclusion, it is of great significance to review the research on the application of EVs in the treatment of CVDs, which lays a foundation for further exploration of the role of EVs, and clarifies the prospect of EVs in the treatment of myocardial injury. [ABSTRACT FROM AUTHOR]

Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research. [ABSTRACT FROM AUTHOR]

The article focuses on nonspecific complaints like fatigue, and dizziness are relatively common among elderly patients presenting to the emergency department. Topics include the appropriate workup of such complaints is not always evident, the significant number of elderly patients presenting with nonspecific symptoms are ultimately diagnosed with serious conditions, and the patients diagnosed with acute coronary syndrome being more likely than younger patients to present without chest pain.

The United States is in the midst of a multifaceted public health crisis, marked by increasing midlife mortality rates among nearly all racial and ethnic groups.[[1]] The burden of this crisis has fallen most heavily among vulnerable populations, particularly individuals with lower levels of income and education.[[2]] Patterns of rising mortality - which vary across time, space, and causes of death - suggest a complex set of underlying causes, many of which may have been operative for decades.[2] How do the findings speak to the potential consequences of other trends in urban housing, in particular gentrification, whose relationship to evictions and health outcomes has thus far been shown to be mixed? America's declining well-being, health, and life expectancy: not just a white problem. 33 Fazel S, Geddes JR, Kushel M. The health of homeless people in high-income countries: descriptive epidemiology, health consequences, and clinical and policy recommendations. [Extracted from the article]

Background: This study aims to accurately estimate influenza‐associated deaths in Poland and their certified cause of death, due to significant discrepancies between official numbers and expected impact. Methods: Excess influenza‐associated mortality in Poland from 2000 to 2019 was calculated using Seasonal‐Trend Decomposition Procedure based on LOESS (STL), which can detect non‐linear trends and non‐sinusoidal cycles. Excess mortality was then used as an explanatory variable in a model predicting monthly fluctuations of officially recorded causes of death from 2010 to 2019. Results: A total of 142,000 conservative estimates of influenza‐associated deaths were identified, representing 1.86% of overall mortality. Only 0.61% of influenza‐associated deaths were officially recorded as influenza. Nearly half of certified influenza deaths were attributed to the seasonal baseline mortality, potentially doubling estimated impact based solely on influenza peaks. Influenza‐associated deaths were frequently recorded as respiratory diseases (24.36%), with majority attributed to underlying conditions such as cardiovascular diseases (45.31%), cancer (9.06%), or diabetes (2.66%). Influenza‐associated deaths were more commonly certified as nervous system diseases (1.84%) or mental disorders (1.04%), rather than influenza itself. There was a noticeable impact of influenza on secondary infections, such as meningococcal and gastrointestinal infections. Conclusion: These findings highlight the importance of improved estimation for informing public health policy decisions. [ABSTRACT FROM AUTHOR]

Background: Globally, coronary artery disease (CAD) and cancer are the leading causes of death. Studies focusing on the proportion and spectrum of cancer mortality among CAD patients are lacking. We aim to characterize the proportion and spectrum of cancer‐specific mortality among patients with CAD. Methods: We analyzed 93,797 hospitalized survivors with angiographically documented CAD between 2007 and 2020 (mean age: 62.8 ± 11.1 years, 24.7% female) from Cardiorenal ImprovemeNt II (CIN‐II) cohort. Results: During the median follow‐up of 4.8 years (IQR: 2.6–7.5), 13,162 (14.0%) patients died after discharge. A total of 1223/7703 (15.8% of cause‐specific death) CAD patients died of cancer. The three most common types of cancer‐specific death were lung (36.1%), liver (13.3%), and colorectum cancer (12.8%). Furthermore, male (adjusted HR 2.38, 95% CI: 1.99–2.85) and older (≥60 vs. <60 years, adjusted HR 3.25, 95%CI 2.72–3.88) patients had a significantly increased cancer‐specific mortality. Conclusions: Our data suggest that nearly one‐sixth of death is accounted for cancer among CAD patients within a median follow‐up of 4.8 years. Lung, liver, and colorectum cancer are top three cancer‐specific mortality. Further studies are needed to reduce cancer mortality for CAD patients, especially in older and male ones. Trail Registration: (ClinicalTrials.gov NCT05050877). [ABSTRACT FROM AUTHOR]

Please cite this paper as: Hardelid et al. (2012) Mortality caused by influenza and respiratory syncytial virus by age group in England and Wales 1999-2010. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2012.00345.x. Background: The mortality burden caused by influenza cannot be quantified directly from death certificates because of under-recording; therefore, the estimated number of influenza deaths has to be obtained through statistical modelling. Objective: To estimate the number of deaths caused by influenza and respiratory syncytial virus (RSV) in England and Wales between 1999 and 2010 using a multivariable regression model. Methods: Generalised linear models were used to estimate weekly deaths by age group (<15, 15-44, 45-74 and 75+ years) as a function of positive influenza and RSV isolates. Adjustment was made for temperature variation (using weekly means of daily Central England temperature time series), underlying seasonal variation and temporal trends. The parameters from the model were used to predict the number of deaths caused by influenza and RSV across winter seasons. Results: Between 7000 and 25 000 deaths across all ages were associated with influenza in the winter periods 1999-2009. The mortality burden was the highest among the over 75 age group, among whom 2·5-8·1% of deaths were caused by influenza. The lowest number of influenza deaths was estimated for the winter 2009/2010 when pandemic influenza A/H1N1 (2009) was the predominant circulating strain. RSV accounted for 5000-7500 deaths each winter season. Conclusions: The model presented provides a robust and reasonable approach to estimating the number of deaths caused by influenza and RSV by age group at the end of each winter. [ABSTRACT FROM AUTHOR]

Please cite this paper as: He et al. (2012) Mucosal antibody responses are directed by viral burden in children with acute influenza infection. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2012.00346.x. Background Influenza infection causes excess hospitalizations and deaths in younger patients, but susceptibility to severe disease is poorly understood. While mucosal antibodies can limit influenza-associated infection and disease, little is known about acute mucosal antibody responses to influenza infection. Objectives These studies characterize mucosal antiviral antibody production in children during lower respiratory infection (LRI) with H1N1 influenza versus other viral LRI and examine the relationship between mucosal antiviral antibodies and protection against severe disease. Methods B lymphocytes were assessed by immunohistochemistry in lung tissue from infants with fatal acute seasonal influenza infection. Nasopharyngeal secretions (NPS) were obtained at presentation from children with acute respiratory illness, including H1N1 (2009) influenza infection. Total and antiviral antibodies, and inflammatory and immune mediators, were quantified by ELISA. Neutralizing activity in NPS was detected using a pseudotyped virus assay. Viral burden was assessed by qPCR. Results and conclusions B lymphocytes were abundant in lung tissue of infants with fatal acute influenza LRI. Among surviving children with H1N1 infection, only a small subset (11%) demonstrated H1N1 neutralizing activity in NPS. H1N1 neutralizing activity coincided with high local levels of antiviral IgM, IgG and IgA, greater detection of inflammatory mediators, and higher viral burden ( P = 0·016). Patients with mucosal antiviral antibody responses demonstrated more severe respiratory symptoms including greater hypoxia ( P = 0·0018) and pneumonia ( P = 0·038). These patients also trended toward younger age, longer duration of illness and longer hospital stays. Prophylaxis strategies that heighten neutralizing antibody production in the mucosa are likely to benefit both older and younger children. [ABSTRACT FROM AUTHOR]

ABSTRACT Surveys in different countries (e.g. the UK, Belgium and The Netherlands) show a marked recent increase in the incidence of continuous deep sedation at the end of life (CDS). Several hypotheses can be formulated to explain the increasing performance of this practice. In this paper we focus on what we call the 'natural death' hypothesis, i.e. the hypothesis that acceptance of CDS has spread rapidly because death after CDS can be perceived as a 'natural' death by medical practitioners, patients' relatives and patients. We attempt to show that the label 'natural' cannot be unproblematically applied to the nature of this end-of-life practice. We argue that the labeling of death following CDS as 'natural' death is related to a complex set of mechanisms which facilitate the use of this practice. However, our criticism does not preclude the view that CDS may be clinically and ethically justified in many cases. [ABSTRACT FROM AUTHOR]

There has been much debate regarding the ‘double-effect’ of sedatives and analgesics administered at the end-of-life, and the possibility that health professionals using these drugs are performing ‘slow euthanasia.’ On the one hand analgesics and sedatives can do much to relieve suffering in the terminally ill. On the other hand, they can hasten death. According to a standard view, the administration of analgesics and sedatives amounts to euthanasia when the drugs are given with an intention to hasten death. In this paper we report a small qualitative study based on interviews with 8 Australian general physicians regarding their understanding of intention in the context of questions about voluntary euthanasia, assisted suicide and particularly the use of analgesic and sedative infusions (including the possibility of voluntary or non-voluntary ‘slow euthanasia’). We found a striking ambiguity and uncertainty regarding intentions amongst doctors interviewed. Some were explicit in describing a ‘grey’ area between palliation and euthanasia, or a continuum between the two. Not one of the respondents was consistent in distinguishing between a foreseen death and an intended death. A major theme was that ‘slow euthanasia’ may be more psychologically acceptable to doctors than active voluntary euthanasia by bolus injection, partly because the former would usually only result in a small loss of ‘time’ for patients already very close to death, but also because of the desirable ambiguities surrounding causation and intention when an infusion of analgesics and sedatives is used. The empirical and philosophical implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Background: The great majority of post-infarction studies of beta-blockers were conducted in an era when these agents were widely held to be contra-indicated for the management of heart failure. We now know that beta-blockers are highly effective for the management of patients with chronic stable heart failure. However, there remains uncertainty about their role in the setting of post-infarction heart failure and ventricular dysfunction.Aim: the primary objective in this paper, was to investigate the extent to which heart failure or evidence of major cardiac dysfunction influenced outcome in previous trials of beta-blockers in heart failure after myocardial infarction.Methods: We assessed the extent to which the inclusion of patients with heart failure or major cardiac dysfunction influenced outcome in randomised trials of long-term use of beta-blockade after myocardial infarction. The primary analysis was to assess the extent to which the proportion of patients included in each trial with heart failure influenced the relative odds of all-cause mortality in the trials. All randomised trials without crossover with treatment lasting more than one month and with 50 or more patients were considered. All those that provided information on the proportion of patients with heart failure or major cardiac dysfunction in the original or subsequent articles were included in the analysis.Results: Overall treatment with a beta-blocker was associated with a 22.6% reduction in the odds of death (95% C1 11-32.3%). There were very few data on the effects of beta-blockers after myocardial infarction in patients with documented left ventricular systolic dysfunction. In the analysis that included heart failure as a factor, treatment with a beta-blocker was associated with a non-significant interaction with the presence of heart failure. However, because the group including heart failure patients were at higher risk, the absolute benefit of treatment with beta-blockers appeared greater in this group.Conclusions: This analysis suggests that the relative benefit of beta-blockers on mortality after a myocardial infarction is similar in the presence or absence of heart failure but that the absolute benefit may be greater in the former. However, as current clinical practice has changed radically from the time when the majority of these trials were conducted, further trial evidence would be desirable. [ABSTRACT FROM AUTHOR]

Aim: To explore the relationship between the serum sodium level on admission and all‐cause mortality in HF patients. Design: A single‐center retrospective cohort study. Methods: Patients hospitalized with HF at the Heart Failure Center, Fuwai Hospital, from November 2008 to November 2018 were enrolled. Results: A total of 3649 patients were included, and the mean sodium level was 137.19 ± 4.36 mmol/L, with a range from 115.6 to 160.9 mmol/L. During a median follow‐up of 1101 days, mortality occurred in 1413 (38.7%) hospital survivors. After adjustment for age, sex, and other potential confounders, patients with sodium levels <135 mmol/L (hazard ratio [HR]: 1.67; 95% confidence interval [CI]: 1.29–2.16) and 135–137 mmol/L (HR: 1.34; 95% CI: 1.01–1.78) had an increased risk of all‐cause mortality compared to those with sodium levels of 139–141 mmol/L. [ABSTRACT FROM AUTHOR]

Numerous publications have stated that metastases are responsible for 90% of cancer deaths, but data underlying this assertion has been lacking. Our objective was to determine what proportions of cancer deaths are caused by metastases. Population‐based data from the Cancer Registry of Norway for the years 2005‐2015 was analyzed. We compared all deaths in the Norwegian population where a cancer diagnosis was registered as cause of death. Deaths caused by cancer, with and without metastases, were analyzed, by sex and tumor group. For solid tumors, 66.7% of cancer deaths were registered with metastases as a contributing cause. Proportions varied substantially between tumor groups. Our data support the idea that the majority of deaths from solid tumors are caused by metastases. Thus, a better understanding of the biology of metastases and identification of druggable targets involved in growth at the metastatic site is a promising strategy to reduce cancer mortality. [ABSTRACT FROM AUTHOR]

Objective: To report multiple cause of death (MCOD) occurrence among patients in the United States with amyotrophic lateral sclerosis (ALS). Methods: Using death certificate data for all ALS deaths from 50 U.S. states and the District of Columbia, 2011–2014, we tabulated MCOD, used association rules mining (ARM) to determine if MCOD occurred together, and calculated standardized mortality odds ratios (SMOR) for select causes, comparing ALS with other U.S. decedents. Results: Among 24,328 death certificates, there were 25,704 MCOD, excluding ALS. ALS was listed as the sole cause of death in n = 11,263 (46%). The most frequent causes of death co‐occurring with ALS were respiratory failure (n = 6503; 25.3%), cardiovascular disease (n = 6077; 12.6%), pneumonia (n = 1345; 5.2%), and pneumonitis (n = 856; 3.3%). The SMORs among ALS decedents compared with non‐ALS decedents for falls and accidents were 3.4 (95% CI 2.6, 4.3) and 3.0 (95% CI 2.2, 4.2), respectively. From ARM analysis, falls and accidents were both associated with injuries. The most common causes identified were weakly to very strongly associated with being an ALS decedent compared with other U.S. deaths, with SMOR point estimates ranging from 1.3 to 51.1. Interpretation: This study provides information about the natural history of ALS. With knowledge that some causes of death may be preventable, healthcare providers may be able to optimize patient care and possibly postpone mortality and reduce morbidity. Moreover, this study located gaps in data; medical certifiers completing death certificates for ALS decedents should ensure all MCOD data are recorded. [ABSTRACT FROM AUTHOR]

Background: There are no previous reports on the main causes of death in biliary tract cancer (BTC) patients. This study aimed to evaluate the main causes of death and survival rates in patients with BTC. Methods: We retrospectively evaluated 143 patients who were diagnosed with unresectable BTC between August 2010 and March 2020. We classified the main causes of death based on laboratory data, imaging studies, and medical records. The main causes of death evaluated included liver failure, cholangitis, cachexia, other causes associated with tumor progression, and complications. We also analyzed survival rates for each main cause of death. Results: After excluding patients who were lost to follow‐up, living patients, and patients who had no records of laboratory data within 30 days before the date of death, 108 patients were analyzed. The main cause of death was cholangitis in 33 (30.6%), cachexia in 22 (20.4%), liver failure in 10 (9.3%), other causes associated with tumor progression in 18 (16.7%), and complications in 25 (23.2%) patients. Median overall survival (OS) was 334.0 days in the chemotherapy group and 75.0 days in the best supportive care (BSC) group. Survival analyzed according to the main cause of death was significantly different between the chemotherapy and BSC groups; OS for cachexia, cholangitis, liver failure, other causes associated with tumor progression, and complications, respectively, were 453.0, 499.0, 567.0, 205.0, and 327.5 days (p = 0.003) in the chemotherapy group and 219.0, 69.0, 34.0, 93.0, and 56.0 days (p = 0.001) in the BSC group. Conclusion: The main causes of death in patients with advanced BTC are cholangitis, cachexia, liver failure, other causes associated with tumor progression, and complications. Other causes associated with tumor progression in the chemotherapy group, and liver failure in the BSC group as the main causes of death shortened the survival of BTC patients. [ABSTRACT FROM AUTHOR]

Introduction: The death of a baby is devastating for parents, families and staff involved. Involving bereaved parents in their baby's care and in the maternity hospital perinatal death review can help parents manage their bereavement and plan for the future. In Ireland, bereaved parents generally have not been involved in this review process. The aim of our study was to assess parents' perception of how they may be appropriately involved in the maternity hospital perinatal death review in ways that benefit them and the review process itself. Methods: Bereaved parents (n = 20) in Ireland were invited to take part in semistructured interviews. Thematic analysis was carried out on the interview transcripts. Results: Four main themes were identified based on the participants' views and opinions on how they experienced the review process and how they feel this process may be improved. The themes reflect the journey of the parents through the different stages of the review process: Throughout process; On leaving the hospital; Interaction with the hospital 'waiting in limbo'; Review itself. Identified subthemes highlighted essential aspects of this process and care provided to parents. For the parents, open, honest communication with staff, as well as having a key hospital contact was essential. Parents wished to provide feedback on their experience and wanted to be included in the review of their baby's death, in a way that was sensitive to their needs and the hospital's schedule. Conclusion: A respectful, flexible system that allows bereaved parents' involvement in their baby's perinatal death review and is tailored to their needs is essential. A collaborative process between staff and parents can highlight clinical areas in need of change, enhance lessons learned, improve bereavement services and may prevent future perinatal deaths. Public Contribution: Bereaved parents were interviewed for this study. [ABSTRACT FROM AUTHOR]

Summary: Problem: The prevalence of epilepsy is high in many areas of Africa. This condition is stigmatized, and there are limited health personnel and facilities for diagnosis and treatment. A huge treatment gap is suspected for epilepsy, and data suggest that nearly 80–85% of people with epilepsy have never been diagnosed or treated. It is reported worldwide that the mortality among people with epilepsy is two- to threefold higher than in general population. An increase of at least this magnitude is suspected in Africa, but there are very few data. Verbal autopsy studies may be one way of carrying out studies of mortality for epilepsy in Africa because these methods do not rely on autopsies, which are rare, or upon death certificates, which are a poor source of information on death in Africa. Methods: This paper presents the literature on mortality after seizures in Africa, although there are few studies of mortality among people with epilepsy in Africa. Results: The existing studies suggest an increased risk of dying and a greater proportion of deaths that are epilepsy-related. One study reports a sixfold increase in mortality in people with epilepsy. This is higher than the two- to threefold increase reported in developed countries. Conclusions: Considering the high prevalence of this condition, the public health impact of epilepsy mortality is likely to be enormous. [ABSTRACT FROM AUTHOR]

The urgent need for appropriate treatment for suicide, the tenth leading cause of death, has led to numerous studies. This study aims to systematically identify and appraise systematic reviews with or without meta‐analyses investigating ketamine in suicidal ideation and behaviours. Scopus, ISI, Embase, PubMed, CINAHL, PsycINFO, Cochrane Library, Google Scholar and two registries were searched without any restrictions for systematic reviews investigating the efficacy of ketamine on suicidal ideation and behaviours. The primary outcome was the final inference of ketamine effectiveness. A formal narrative synthesis was conducted, and the AMSTAR‐2 tool was used to evaluate the quality of the studies. Of 27 studies that addressed ketamine for suicidal ideation, only four reported mixed or negative results, and out of nine reviews, esketamine was significantly beneficial only in five. A transient rise in pulse rate and blood pressure, dissociation, confusion, blurred vision, nausea and vertigo were the most common adverse effects; however, most were mild. More than two‐thirds of the included studies qualified as of low or critically low quality. Preliminary evidence for the short‐term efficacy of ketamine in suicidality was noted by the majority of reviews; however, long‐term effects remained unknown. Due to the low quality of many studies and the limitations of core studies, further research is required. [ABSTRACT FROM AUTHOR]

Adaptive plasticity in life‐history traits is often critical to maximize fitness in the face of environmental heterogeneity. For example, many organisms respond to a threat to their survival (and hence residual reproductive value) by adaptively increasing their investment into current reproduction (i.e. 'terminal investment').A key to successful terminal investment is the use of adequate environmental cues to extrinsic mortality sources. In species that live at high population densities, the presence of dead conspecifics could potentially act as a reliable cue to extrinsic mortality sources (e.g. via pathogens).We experimentally tested this idea using the model organism Drosophila melanogaster, a pest species that experiences marked demographic shifts. We monitored the reproductive output of young mated females during repeated bouts of egg laying in the presence (i.e. dead exposed) or absence (i.e. controls) of dead conspecifics, interspersed by mating periods where dead conspecifics were always absent.Dead‐exposed females produced more offspring than controls when in the presence of dead conspecifics but fewer offspring than controls when dead conspecifics were subsequently removed (i.e. during mating periods). These changes were repeatable across time, and are thus indicative of high plasticity in reproductive behaviour induced by perception of dead conspecifics.Flies responded equally to starvation‐induced and flash‐frozen dead conspecifics, indicating that the cause of death is irrelevant to trigger the plastic response observed, and that females respond to the presence of dead conspecifics per se.Finally, we found that dead‐exposed females produced heavier daughters (but not sons) than controls when in the presence of dead conspecifics, but not during mating periods (when dead conspecifics were absent). In this species, body size correlates more strongly with female (than male) fitness, so higher investment in daughter weight is congruent with terminal investment.Altogether, these results show that perception of dead conspecifics leads to highly plastic life‐history adjustments in the form of increased investment in both the quantity and the quality of offspring. We discuss these results in the context of terminal investment and other alternative hypotheses. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

Background: Seasonal influenza‐associated excess mortality estimates can be timely and provide useful information on the severity of an epidemic. This methodology can be leveraged during an emergency response or pandemic. Method: For Denmark, Spain, and the United States, we estimated age‐stratified excess mortality for (i) all‐cause, (ii) respiratory and circulatory, (iii) circulatory, (iv) respiratory, and (v) pneumonia, and influenza causes of death for the 2015/2016 and 2016/2017 influenza seasons. We quantified differences between the countries and seasonal excess mortality estimates and the death categories. We used a time‐series linear regression model accounting for time and seasonal trends using mortality data from 2010 through 2017. Results: The respective periods of weekly excess mortality for all‐cause and cause‐specific deaths were similar in their chronological patterns. Seasonal all‐cause excess mortality rates for the 2015/2016 and 2016/2017 influenza seasons were 4.7 (3.3–6.1) and 14.3 (13.0–15.6) per 100,000 population, for the United States; 20.3 (15.8–25.0) and 24.0 (19.3–28.7) per 100,000 population for Denmark; and 22.9 (18.9–26.9) and 52.9 (49.1–56.8) per 100,000 population for Spain. Seasonal respiratory and circulatory excess mortality estimates were two to three times lower than the all‐cause estimates. Discussion We observed fewer influenza‐associated deaths when we examined cause‐specific death categories compared with all‐cause deaths and observed the same trends in peaks in deaths with all death causes. Because all‐cause deaths are more available, these models can be used to monitor virus activity in near real time. This approach may contribute to the development of timely mortality monitoring systems during public health emergencies. [ABSTRACT FROM AUTHOR]

Heart failure is a clinical syndrome caused by ventricular insufficiency, which results in decreased activity tolerance and repeated hospitalization, seriously affecting quality of life, and it is the main cause of death in elderly people. In recent years, great progress has been made in the treatment of heart failure, but the prevalence, mortality, and readmission rate among elderly patients with heart failure remain high. Because elderly patients have multiple cardiovascular disease risk factors, coexistence of multiple diseases accompanied by multiple syndromes, multiple medications, and natural decline of body functions, the clinical diagnosis, treatment, rehabilitation, and long‐term management of these patients differ from those in other populations. To facilitate clinical practice and application of clinical geriatric medicine, especially among community physicians, experts from the Cardiovascular Group, Geriatrics Branch of the Chinese Medical Association have drafted this consensus to summarize the diagnosis and treatment regimens for elderly patients with chronic heart failure and provide guidance for its clinical diagnosis and treatment in China. [ABSTRACT FROM AUTHOR]

In the United States, the Bald and Golden Eagle Protection Act prohibits take of golden eagles (Aquila chrysaetos) unless authorized by permit, and stipulates that all permitted take must be sustainable. Golden eagles are unintentionally killed in conjunction with many lawful activities (e.g., electrocution on power poles, collision with wind turbines). Managers who issue permits for incidental take of golden eagles must determine allowable take levels and manage permitted take accordingly. To aid managers in making these decisions in the western United States, we used an integrated population model to obtain estimates of golden eagle vital rates and population size, and then used those estimates in a prescribed take level (PTL) model to estimate the allowable take level. Estimated mean annual survival rates for golden eagles ranged from 0.70 (95% credible interval = 0.66–0.74) for first‐year birds to 0.90 (0.88–0.91) for adults. Models suggested a high proportion of adult female golden eagles attempted to breed and breeding pairs fledged a mean of 0.53 (0.39–0.72) young annually. Population size in the coterminous western United States has averaged ~31,800 individuals for several decades, with λ = 1.0 (0.96–1.05). The PTL model estimated a median allowable take limit of ~2227 (708–4182) individuals annually given a management objective of maintaining a stable population. We estimate that take averaged 2572 out of 4373 (59%) deaths annually, based on a representative sample of transmitter‐tagged golden eagles. For the subset of golden eagles that were recovered and a cause of death determined, anthropogenic mortality accounted for an average of 74% of deaths after their first year; leading forms of take over all age classes were shooting (~670 per year), collisions (~611), electrocutions (~506), and poisoning (~427). Although observed take overlapped the credible interval of our allowable take estimate and the population overall has been stable, our findings indicate that additional take, unless mitigated for, may not be sustainable. Our analysis demonstrates the utility of the joint application of integrated population and prescribed take level models to management of incidental take of a protected species. [ABSTRACT FROM AUTHOR]

Background: There are no reports on the number of fatalities or causes of death in the Norwegian and Swedish harness racehorses. Objectives: The incidence rates (IRs), risk factors, and postmortem findings in horses that died or were euthanized associated with racing between 2014 and 2019 were investigated. Animals: Thirty‐eight Standardbreds and 10 Norwegian‐Swedish Coldblooded Trotters died or were euthanized associated with racing. A total of 816 085 race‐starts were recorded. Methods: Incidence rates were calculated for both countries and horse breeds. Risk factors for sudden death were identified using a case‐control logistic model. Postmortem examinations were performed in 43 horses. Results: The overall fatality IR was 0.059/1000 race‐starts. Traumatic injuries accounted for 14.5%, while sudden death for 85.5% of fatalities. Only minor differences between countries and breeds were recorded. The number of starts within the last 30 days increased the risk of sudden death (5 starts odds ratio (OR) 228.80, confidence interval (CI) 10.9‐4793). An opposite non‐linear effect was observed in number of starts the last 180 days (>10 starts OR 0.12, CI 0.02‐0.68). Seven horses were euthanized because of catastrophic injury. Acute circulatory collapse because of suspected cardiac or pulmonary failure or both was recorded in 30 horses, while major hemorrhage after vessel rupture was the primary cause of death in 10 cases. One horse collapsed and died but was not submitted for autopsy. Conclusions and Clinical Importance: Comparatively low rates of catastrophic orthopedic fatalities were reported, while causes and IR of sudden death were similar to previous studies. [ABSTRACT FROM AUTHOR]

Infection is the second leading cause of death in patients with cancer. Loss of efficacy in antibiotics due to antibiotic resistance in bacteria is an urgent threat against the continuing success of cancer therapy. In this review, the authors focus on recent updates on the impact of antibiotic resistance in the cancer setting, particularly on the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.). This review highlights the health and financial impact of antibiotic resistance in patients with cancer. Furthermore, the authors recommend measures to control the emergence of antibiotic resistance, highlighting the risk factors associated with cancer care. A lack of data in the etiology of infections, specifically in oncology patients in United States, is identified as a concern, and the authors advocate for a centralized and specialized surveillance system for patients with cancer to predict and prevent the emergence of antibiotic resistance. Finding better ways to predict, prevent, and treat antibiotic‐resistant infections will have a major positive impact on the care of those with cancer. [ABSTRACT FROM AUTHOR]

Copyright of British Journal of Clinical Pharmacology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The occurrence of cardiovascular events is a major cause of death in patients with cancer. Small studies have documented a connection between specific brain alterations and autonomic cardiac dysfunctions, possibly resulting in a worse prognosis. We aimed to refine the knowledge of fatal cardiac events in patients with brain metastasis (BM). Methods: We performed a Surveillance, Epidemiology, and End Results SEER registry‐based investigation (timeline: 2010–2016) and extracted all the advanced patients who had experienced fatal cardiac outcomes. Populations were compared according to the presence or not BM. Kaplan–Meier (KM) methodology was used for survival analysis and a multivariate model was developed by adjusting for multiple possible confounders. Results: Most related BM and cardiac death were observed at the site of lung cancer (81.4%). We extracted 3187 patients with lung cancer site, including 417 patients who had experienced fatal heart‐specific with a history of BM, which is considered a BM group. The second group of heart‐specific death included 2770 patients was stated as a non‐BM group. Patients who had experienced heart‐specific death in the BM group were predominately male, right side, upper site, and non‐small type (62.11%, 54.92%, 51.56%, 69.78%), respectively. The survival outcomes between BM and the non‐ BM was significantly prominent (p = 0.003; median: 2 months vs. 3 months).The negative prognostic independent significance of heart‐fatal events was confirmed after adjusting for multiple variables (HR = 0.76, CI = 0.68–84, p < 0.0001). The metastatic liver site was significantly associated with poorer survival rates (HR = 0.68; CI = 0.52–0.88, p = 0.005). We revealed a possible connection between the brain and heart functions. Conclusions: The prognosis of heart‐specific death patients in BM is unfavorable compared to non‐BM settings in lung cancer. We may be at the gates of a new field of neurocardiooncology. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the magnitude of under‐reporting the number of deaths due to COVID‐19 in Brazil in 2020, previously shown to occur due to low rate of laboratory testing for SARS‐CoV‐2, reporting delay, inadequate access to medical care, and its poor quality, leading to the low sensitivity of epidemiological surveillance and poor outcomes, often without laboratory confirmation of the cause of death. Methods: Excess mortality due to COVID‐19 was estimated directly based on various data sources, and indirectly, based on the difference between the observed and expected number of deaths from serious acute respiratory infection (SARI) and all‐natural causes in 2020 had there been no COVID‐19. The absence of laboratory testing for SARS‐CoV‐2 was adjusted based on the proportion of those who tested positive among the tested individuals whose death was attributed to COVID‐19. Least absolute shrinkage and selection operator (lasso) were used to improve prediction of likely mortality without COVID‐19 in 2020. Results: Under‐reporting of COVID‐19 deaths was 22.62%, with a corresponding mortality rate per 100 000 inhabitants of 115 by the direct method, 71–76 by the indirect methods based on the excess SARI mortality and 95–104 by excess mortality due to natural causes. COVID‐19 was the third cause of mortality that contributed directly with 18%, and indirectly with additional 10–11% to all deaths in Brazil in 2020. Conclusions: Underestimation of COVID‐19 mortality between 1:5 and 1:4 is likely its lower bound. Timely and accurate surveillance of death causes is of the essence to evaluate the COVID‐19 burden. [ABSTRACT FROM AUTHOR]

Introduction: Misclassification of HIV deaths can substantially diminish the usefulness of cause of death data for decision‐making. In this study, we describe the methods developed by the Global Burden of Disease Study to account for the misclassified cause of death data from vital registration systems for estimating HIV mortality in 132 countries and territories. Methods: The cause of death data were obtained from the World Health Organization Mortality Database and official country‐specific mortality databases. We implemented two steps to adjust the raw cause of death data: (1) redistributing garbage codes to underlying causes of death, including HIV/AIDS by applying methods, such as analysis of multiple cause data and proportional redistribution, and (2) reassigning HIV deaths misclassified as other causes to HIV/AIDS by examining the age patterns of underlying causes in location and years with and without HIV epidemics. Results: In 132 countries, during the period from 1990 to 2018, 1,848,761 deaths were reported as caused by HIV/AIDS. After garbage code redistribution in these 132 countries, this number increased to 4,165,015 deaths. An additional 1,944,291 deaths were added through correction of HIV deaths misclassified as other causes in 44 countries. The proportion of HIV deaths derived from garbage code redistribution decreased over time, from 0.4 in 1990 to 0.1 in 2018. The proportion of deaths derived from HIV misclassification correction peaked at 0.4 in 2006 and declined afterwards to 0.08 in 2018. The greatest contributors to garbage code redistribution were "immunodeficiency antibody" (ICD 9: 279‐279.1; ICD 10: D80‐D80.9) and "immunodeficiency other" (ICD 9: 279, 279.5‐279.9; ICD 10: D83‐D84.9, D89, D89.8‐D89.9), which together contributed 77% of all redistributed deaths at their peak in 1995. Respiratory tuberculosis (ICD 9: 010–012.9; ICD 10: A10‐A14, A15‐A16.9) contributed the greatest proportion of all HIV misclassified deaths (25–62% per year) over the most years. Conclusions: Correcting for miscoding and misclassification of cause of death data can enhance the utility of the data for analyzing trends in HIV mortality and tracking progress toward the Sustainable Development Goal targets. [ABSTRACT FROM AUTHOR]

Introduction: : Tuberculosis (TB) remains the most common cause of death among people living with HIV. Integrating HIV and TB services reduces mortality but is sub‐optimally implemented. Quality improvement (QI) methods offer a low‐cost and easily implementable approach to strengthening healthcare delivery systems. This trial assessed a QI intervention on key process indicators for delivering integrated HIV‐TB care in rural South African primary healthcare (PHC) clinics. Methods: Sixteen nurse supervisors, (each with a cluster of clinics) overseeing 40 PHC clinics, were randomized 1:1 to the intervention or the standard of care (SOC) groups. The QI intervention comprised three key components: clinical and QI skills training, on‐site mentorship of nurse supervisors and clinic staff, and data quality improvement activities to enhance accuracy and completeness of routine clinic data. The SOC comprised monthly supervision and data feedback meetings. From 01 December 2016 to 31 December 2018, data were collected monthly by a team of study‐appointed data capturers from all study clinics. This study's outcomes were HIV testing services (HTS), TB screening, antiretroviral therapy (ART) initiation, isoniazid preventive therapy (IPT) initiation and viral load (VL) testing. Results: The QI group (eight clusters) comprised 244 clinic staff who attended to 13,347 patients during the trial compared to the SOC group (eight clusters) with 217 clinic staff who attended to 8141 patients. QI mentors completed 85% (510/600) of expected QI mentorship visits to QI clinics. HTS was 19% higher [94.5% vs. 79.6%; relative risk (RR)=1.19; 95% CI: 1.02–1.38; p=0.029] and IPT initiation was 66% higher (61.2 vs. 36.8; RR=1.66; 95% CI: 1.02–2.72; p=0·044), in the QI group compared to SOC group. The percentage of patients screened for TB (83.4% vs. 79.3%; RR=1.05; p=0.448), initiated on ART (91.7 vs. 95.5; RR=0.96; p=0.172) and VL testing (72.2% vs. 72.8%; RR=0.99; p=0.879) was similar in both groups. Conclusions: QI improved HIV testing and IPT initiation compared to SOC. TB screening, ART initiation and VL testing remained similar. Incorporating QI methods into routine supervision and support activities may strengthen integrated HIV‐TB service delivery and increase the success of future QI scale‐up activities. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?The current literature indicates that oxidative stress plays a major role in iron overload. Although exercise is a well‐established approach to treat/prevent cardiovascular diseases, its effects on iron overload are not known.What is the main finding and its importance?Moderate‐intensity aerobic training had benefits in a rodent model of iron‐overload cardiomyopathy by improving the antioxidant capacity of the heart. After further confirmation by translational and clinical studies, we should consider using this non‐pharmacological, highly accessible and easily executable adjuvant approach allied to other therapies to improve the quality of life of iron‐overloaded patients. Iron is an essential micronutrient for several life processes, but its excess can damage organs owing to oxidative stress, with cardiomyopathy being the leading cause of death in iron‐overloaded patients. Although exercise has long been considered as a cardioprotective tool, its effects on iron overload are not known. This study was designed to investigate the effects of moderate‐intensity aerobic training in rats previously submitted to chronic iron overload. Wistar rats received i.p. injections of iron dextran (100 mg/kg, 5 days/week for 4 weeks); thereafter, the rats were kept sedentary or exercised (60 min/day, progressive aerobic training, 60–70% of maximal speed, 5 days/week on a treadmill) for 8 weeks. At the end of the experimental period, haemodynamics were recorded and blood samples, livers and hearts harvested. Myocardial mechanics of papillary muscles were assessed in vitro, and cardiac remodelling was evaluated by histology and immunoblotting. Iron overload led to liver iron deposition, liver fibrosis and increased serum alanine aminotransferase and aspartate aminotransferase. Moreover, cardiac iron accumulation was accompanied by impaired myocardial mechanics, increased cardiac collagen type I and lipid peroxidation (TBARS), and release of creatine phosphokinase‐MB to the serum. Although exercise did not influence iron levels, tissue injury markers were significantly reduced. Likewise, myocardial contractility and inotropic responsiveness were improved in exercised rats, in association with an increase in the endogenous antioxidant enzyme catalase. In conclusion, moderate‐intensity aerobic exercise was associated with attenuated oxidative stress and cardiac damage in a rodent model of iron overload, thereby suggesting its potential role as a non‐pharmacological adjuvant therapy for iron‐overload cardiomyopathy. [ABSTRACT FROM AUTHOR]

The influence of the central nervous system and autonomic system on cardiac activity is being intensively studied, as it contributes to the high rate of cardiologic comorbidities observed in people with epilepsy. Indeed, neuroanatomic connections between the brain and the heart provide links that allow cardiac arrhythmias to occur in response to brain activation, have been shown to produce arrhythmia both experimentally and clinically. Moreover, seizures may induce a variety of transient cardiac effects, which include changes in heart rate, heart rate variability, arrhythmias, asystole, and other ECG abnormalities, and can trigger the development of Takotsubo syndrome. People with epilepsy are at a higher risk of death than the general population, and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy‐related cause of death. Although the cause of SUDEP is still unknown, cardiac abnormalities during and between seizures could play a significant role in its pathogenesis, as highlighted by studies on animal models of SUDEP and registration of SUDEP events. Recently, genetic mutations in genes co‐expressed in the heart and brain, which may result in epilepsy and cardiac comorbidity/increased risk for SUDEP, have been described. Recognition and a better understanding of brain–heart interactions, together with new advances in sequencing techniques, may provide new insights into future novel therapies and help in the prevention of cardiac dysfunction and sudden death in epileptic individuals. [ABSTRACT FROM AUTHOR]

We present the hypothesis that advanced stage cancer is also a heart failure syndrome. It can develop independently of or in addition to cardiotoxic effects of anti‐cancer therapies. This includes an increased risk of ventricular arrhythmias. We suggest the pathophysiologic link for these developments includes generalized muscle wasting (i.e. sarcopenia) due to tissue homeostasis changes leading to cardiac wasting associated cardiomyopathy. Cardiac wasting with thinning of the ventricular wall increases ventricular wall stress, even in the absence of ventricular dilatation. In addition, arrhythmias may be facilitated by cellular wasting processes affecting structure and function of electrical cells and conduction pathways. We submit that in some patients with advanced cancer (but not terminal cancer), heart failure therapy or defibrillators may be relevant treatment options. The key points in selecting patients for such therapies may be the predicted life expectancy, quality of life at intervention time, symptomatic burden, and consequences for further anti‐cancer therapies. The cause of death in advanced cancer is difficult to ascertain and consensus on event definitions in cancer is not established yet. Clinical investigations on this are called for. Broader ethical considerations must be taken into account when aiming to target cardiovascular problems in cancer patients. We suggest that focused attention to evaluating cardiac wasting and arrhythmias in cancer will herald a further evolution in the rapidly expanding field of cardio‐oncology. [ABSTRACT FROM AUTHOR]

Carbon monoxide (CO) is the leading cause of death by poisoning worldwide. The aim was to explore the effects of mild and severe poisoning on blood gas parameters and metabolites. Eleven pigs were exposed to CO intoxication and had blood collected before and during poisoning. Mild CO poisoning (carboxyhaemoglobin, COHb 35.2 ± 7.9%) was achieved at 32 ± 13 minutes, and severe poisoning (69.3 ± 10.2% COHb) at 64 ± 23 minutes from baseline (2.9 ± 0.5% COHb). Blood gas parameters and metabolites were measured on a blood gas analyser and nuclear magnetic resonance spectrometer, respectively. Unsupervised principal component, analysis of variance and Pearson's correlation tests were applied. A P‐value ≤.05 was considered statistically significant. Mild poisoning resulted in a 28.4% drop in oxyhaemoglobin (OHb) and 12‐fold increase in COHb, while severe poisoning in a 65% drop in OHb and 24‐fold increase in COHb. Among others, metabolites implicated in regulation of metabolic acidosis (lactate, P <.0001), energy balance (pyruvate, P <.0001; 3‐hydroxybutyrc acid, P =.01), respiration (citrate, P =.007; succinate, P =.0003; fumarate, P <.0001), lipid metabolism (glycerol, P =.002; choline, P =.0002) and antioxidant‐oxidant balance (glutathione, P =.03; hypoxanthine, P <.0001) were altered, especially during severe poisoning. Our study adds new insights into the deranged metabolism of CO poisoning and leads the way for further investigation. [ABSTRACT FROM AUTHOR]

Albatrosses are among the world's most imperiled vertebrates, with 73% of species threatened with extinction. Ingestion of plastic is a well‐recognized threat among three North Pacific species, but lesser known in the southern hemisphere, where it is considered a minor threat. As plastic entering the ocean is increasing while albatross populations decline, the threat of ocean plastic to albatross populations may be underestimated. We present case studies of 107 beach‐cast albatrosses of twelve species, received by wildlife hospitals in Australia and New Zealand, and estimate plastic ingestion and mortality rates for albatrosses in the southern hemisphere. Ingested plastic was present in 5.6% of individuals, and the cause of death in half of these cases. We estimate ingestion of plastic may cause 3.4–17.5% of nearshore mortalities and is worth consideration as a substantial threat to albatross populations. We provide clinical findings and "checklist" methodologies for identifying potential cases of foreign‐body gastrointestinal obstruction. We suggest practical policy responses, empowering decision makers to reduce albatross mortality from anthropogenic sources. [ABSTRACT FROM AUTHOR]

Objective: Sudden unexpected death in epilepsy (SUDEP) is a diagnosis of exclusion; the definition includes individuals with epilepsy who die suddenly without an identifiable toxicological or anatomical cause of death. Limited data suggest underidentification of SUDEP as the cause of death on death certificates. Here, we evaluate the autopsy‐reported cause of death in a population‐based cohort of SUDEP cases. Methods: Case summaries of forensic autopsies conducted in Ontario, Canada between January 2014 and June 2016 were retrospectively screened using a language processing script for decedents with a history of epilepsy or seizures. After manual review for potential SUDEP cases, two neurologists independently examined the autopsy reports and classified deaths by Nashef criteria. Demographic characteristics and consideration by the forensic pathologist of the role of epilepsy, seizure, and SUDEP in death were summarized. Results: One hundred and eight Definite, 34 Definite Plus, and 22 Possible SUDEP cases were identified. Seventy‐five percent of Definite/Definite Plus SUDEP cases identified by the neurologists were attributed to SUDEP, epilepsy, or seizure disorder in the autopsy report. There was a significant association between the proportion of cases listed in the autopsy report as SUDEP, epilepsy, or seizure disorder and neurologists' SUDEP classification (86% of Definite, 38% of Definite Plus, 0% of Possible). Age was significantly associated with SUDEP classification; Definite cases were younger than Definite Plus, which were younger than Possible SUDEP cases. Significance: Most SUDEP cases identified by neurologists were classified concordantly by forensic pathologists in Ontario, Canada; however, concordance decreased with increased case complexity. Although the role of epilepsy/seizures was considered in most Definite/Definite Plus cases, this study highlights the need for autopsy report review of potential SUDEP cases in research studies and assessments of the public health burden of SUDEP. The relationship between age and SUDEP classification has important public health implications; SUDEP incidence may be underappreciated in older adults. [ABSTRACT FROM AUTHOR]

We compared sudden unexpected death in epilepsy (SUDEP) diagnosis rates between North American SUDEP Registry (NASR) epileptologists and original death investigators, to determine degree and causes of discordance. In 220 SUDEP cases with post‐mortem examination, we recorded the epileptologist adjudications and medical examiner‐ and coroner‐ (ME/C) listed causes of death (CODs). COD diagnosis concordance decreased with NASR's uncertainty in the SUDEP diagnosis: highest for Definite SUDEP (84%, n = 158), lower in Definite Plus (50%, n = 36), and lowest in Possible (0%, n = 18). Rates of psychiatric comorbidity, substance abuse, and toxicology findings for drugs of abuse were all higher in discordant cases than concordant cases. Possible SUDEP cases, an understudied group, were significantly older, and had higher rates of cardiac, drug, or toxicology findings than more certain SUDEP cases. With a potentially contributing or competing COD, ME/Cs favored non–epilepsy‐related diagnoses, suggesting a bias toward listing CODs with structural or toxicological findings; SUDEP has no pathognomonic features. A history of epilepsy should always be listed on death certificates and autopsy reports. Even without an alternate COD, ME/Cs infrequently classified COD as "SUDEP." Improved collaboration and communication between epilepsy and ME/C communities improve diagnostic accuracy, as well as bereavement and research opportunities. [ABSTRACT FROM AUTHOR]

Pseudorabies virus (PRV) or suid herpesvirus 1 (SHV‐1) is the causative agent of Aujeszky's disease, a highly contagious viral infection which causes neurological fatal illness in mammals other than suids. Here we report a case of a young wolf (Canis lupus) of around 2 years found dead by a hunter in the province of Avellino, Campania Region. Necropsy showed pathological findings consistent with encephalitis and gastroenteritis. Organs were analysed by microbiological and molecular investigations following standard procedures to ascertain the possible cause of death. Real‐time PCR revealed the presence of PRV in the brain and of canine parvovirus 2b in organs like intestine, liver, brain, kidney and pancreas. Death probably occurred very shortly after SHV‐1 infection in an animal already weakened by parvovirosis. [ABSTRACT FROM AUTHOR]

Uptake of colorectal cancer screening remains suboptimal. Mailed fecal immunochemical testing (FIT) offers promise for increasing screening rates, but optimal strategies for implementation have not been well synthesized. In June 2019, the Centers for Disease Control and Prevention convened a meeting of subject matter experts and stakeholders to answer key questions regarding mailed FIT implementation in the United States. Points of agreement included: 1) primers, such as texts, telephone calls, and printed mailings before mailed FIT, appear to contribute to effectiveness; 2) invitation letters should be brief and easy to read, and the signatory should be tailored based on setting; 3) instructions for FIT completion should be simple and address challenges that may lead to failed laboratory processing, such as notation of collection date; 4) reminders delivered to initial noncompleters should be used to increase the FIT return rate; 5) data infrastructure should identify eligible patients and track each step in the outreach process, from primer delivery through abnormal FIT follow-up; 6) protocols and procedures such as navigation should be in place to promote colonoscopy after abnormal FIT; 7) a high-quality, 1-sample FIT should be used; 8) sustainability requires a program champion and organizational support for the work, including sufficient funding and external policies (such as quality reporting requirements) to drive commitment to program investment; and 9) the cost effectiveness of mailed FIT has been established. Participants concluded that mailed FIT is an effective and efficient strategy with great potential for increasing colorectal cancer screening in diverse health care settings if more widely implemented. [ABSTRACT FROM AUTHOR]

Aims: The prevalence and hospitalizations of patients with heart failure (HF) aged <55 years have increased in Sweden during the last decades. We aimed to compare characteristics of younger and older patients with HF, and examine survival in patients <55 years compared with matched controls.Methods and Results: All patients ≥18 years in the Swedish Heart Failure Register from 2003 to 2014 were included. Data were merged with National Patient and Cause of Death Registers. Among 60 962 patients, 3752 (6.2%) were <55 years, and were compared with 7425 controls from the Population Register. Compared with patients ≥55 years, patients <55 years more frequently had registered diagnoses of obesity, dilated cardiomyopathy, congenital heart disease, and an ejection fraction <40% (9.8% vs. 4.7%, 27.2% vs. 5.5%, 3.7% vs. 0.8%, 67.9% vs. 45.1%, respectively; all P < 0.001). One-year all-cause mortality was 21.2%, 4.2%, and 0.3% in patients ≥55 years, patients <55 years, and controls <55 years, respectively (all P < 0.001). Patients <55 years had a five times higher mortality risk compared with controls [hazard ratio (HR) 5.48, 95% confidence interval (CI) 4.45-6.74]; the highest HR was in patients 18-34 years (HR 38.3, 95% CI 8.70-169; both P < 0.001). At the age of 20, the estimated life-years lost was up to 36 years for 50% of patients, with declining estimates with increasing age.Conclusion: Patients with HF <55 years had different comorbidities than patients ≥55 years. The highest mortality risk relative to that of controls was among the youngest patients. [ABSTRACT FROM AUTHOR]

Objectives: The objective was to evaluate if there is an association between patient–physician language concordance and adverse patient outcomes or physician adherence to clinical recommendations for emergency department (ED) patients with chest pain. Methods: We conducted a retrospective observational study of adult ED chest pain encounters with a troponin order from May 2016 to September 2017 across 15 community EDs. Outcomes were 30‐day acute myocardial infarction or all‐cause mortality, hospital admission/observation, or noninvasive cardiac testing. To assess patient outcomes, we used the overall cohort. To assess adherence to clinical recommendations, we used a subgroup of patients with a low‐risk HEART score. A mixed‐effects logistic regression model was used to compare the odds of the outcomes between language concordant and discordant patient–physician pairs, controlling for patient characteristics. Results: Overall, 52,014 ED encounters were included (10,791 low‐risk HEART encounters). Of those 6,452 (12.4%) encounters were language discordant and 1.7% in each group had an adverse outcome. Adjusted models demonstrated no increased risk for language discordant ED encounters when comparing adverse outcomes (odds ratio [OR] = 0.96, 95% confidence interval [CI] = 0.6 to 1.5) for all patients or recommended care (OR = 1.02, 95% CI = 0.87 to 1.2) for low‐risk patients. Conclusions: No associations were found between patient–physician language concordance and outcomes or physician adherence to clinical recommendations for ED patients with chest pain. Accessible and effective interpretation services, combined with a decision support tool with standard clinical recommendations, may have contributed to equitable care. [ABSTRACT FROM AUTHOR]