Trends in keratinocyte skin cancer incidence, mortality and burden of disease in 33 countries between 1990 and 2017.

BACKGROUND: Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs. Understanding the epidemiological trends for KCs, namely basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs), is required to assess burden of disease, project future trends and identify strategies for addressing this pressing global health issue. OBJECTIVES: To report trends in BCC and SCC incidence, and SCC mortality and disability-adjusted life-years (DALYs). METHODS: An observational study of the Global Burden of Disease (GBD) database between 1990 and 2017 was performed. European Union countries and other selected high-income countries, including the UK and the USA, classified as having high-quality mortality data, were included. Annual age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs) and DALYs for each country were obtained from the GBD database. Trends were described using joinpoint regression analysis. RESULTS: Overall, 33 countries were included. For both BCC and SCC in 2015-2017, the highest ASIRs were observed in the USA and Australia. Males had higher ASIRs than females at the end of the observation period in all countries for SCC, and in all countries but two for BCC. In contrast, the highest ASDRs for SCC were observed in Australia and Latvia for males, and in Romania and Croatia for females. The highest DALYs for SCC for both sexes were seen in Australia and Romania. Over the observation period, there were more countries demonstrating decreasing trends in mortality than in incidence, and disparities were observed between which countries had comparatively high mortality rates and which had high incidence rates. Overall reductions in SCC DALYs were observed in 24 of 33 countries for males, and 25 countries for females. CONCLUSIONS: Over the past 27 years, although trends in SCC incidence have risen in most countries, there is evidence that mortality rates have been decreasing. Burden of disease as assessed using DALYs has decreased in the majority of countries. Future work will explore potential explanatory factors for the observed disparity in trends in SCC incidence and mortality.

As-needed inhaled corticosteroids as add-on therapy versus SMART therapy: an evolving understanding of the two approaches in the management of moderate-to-severe asthma.

PURPOSE OF REVIEW: Asthma is the most common chronic respiratory disorder, characterized by recurring, reversible airflow obstruction due to inflammation and airway hyperresponsiveness. Although biologics have provided significant advances in the treatment of asthma, they are expensive, and their use remains restricted to more severe asthma. Additional approaches in the management of moderate-to-severe asthma are necessary. RECENT FINDINGS: ICS-formoterol as maintenance and reliever therapy in asthma and its effect on improved asthma control has been demonstrated in multiple cohorts of asthma. Although ICS-formoterol as maintenance and reliever therapy has been widely validated, there are significant design considerations including the requirement for exacerbation and bronchodilator response and the lack of evidence for effectiveness in patients who use nebulized reliever therapies, which may limit the use of this therapy in selected populations. More recent trials of as-needed ICS have demonstrated effectiveness in reducing asthma exacerbations and improvements in asthma control and may provide an additional therapeutic strategy for individuals with moderate-to-severe asthma. SUMMARY: Both ICS-formoterol as a maintenance and a reliever as well as as-needed ICS have demonstrated significant improvements in the control of moderate-to-severe asthma. Future investigational work will be necessary to elucidate whether a strategy of ICS-formoterol as maintenance and reliever therapy or an as-needed ICS strategy demonstrates superiority in asthma control in the context of the cost to individual patients and health systems.

Trends in Hospital Admissions, Operative Approaches, and Mortality Related to Abdominal Aortic Aneurysms in England Between 1998 and 2020.

OBJECTIVE: To assess trends in abdominal aortic aneurysm (AAA) hospital admissions, interventions, and aneurysm related mortality in England, and to examine the impact of endovascular repair on mortality for the years 1998 - 2020. METHODS: Hospital admission and operative approach (endovascular aortic aneurysm repair, or open surgical repair [OSR]) using Hospital Episodes Statistics (HES), and aneurysm related mortality data from the Office for National Statistics for England standardised to the 2013 European Standard Population, were analysed using linear regression and Joinpoint regression analyses. Aneurysm related mortality was compared between the pre-endovascular era (1998 - 2010) and the endovascular era (2011 - 2019). RESULTS: A declining trend in hospital admission incidence was observed, mainly due to a decline in ruptured admissions from 34.6 per 100 000 (95% confidence interval [CI] 33.5 - 35.6) to 13.5 per 100 000 (95% CI 12.9 - 14.2; ßi = -1.04, r2 = .97, p < .001). Operative interventions have been declining over the last 23 years mainly due to the statistically significant decline in open procedures (41.2 per 100 000 in 2000 [95% CI 40 - 42.3] to 9.6 per 100 000 [95% CI 9.1 - 10.1]; ßi = -1.92, r2 = .95; p < .001). There was an increasing trend toward endovascular procedures (5.8 per 100 000 [95% CI 5.3 - 6.2] in 2006 to 16.9 per 100 000 [95% CI 16.2 - 17.5] in 2020; ßi = .82, r2 = .30, p = .040). Reductions in aneurysm related mortality due to AAAs were observed for males and females, irrespective of age and rupture status. CONCLUSION: A significant decrease in hospital admissions for AAAs was observed over the last 23 years in England, paralleled by a shift toward endovascular repair and a decline in OSR. Declines in aneurysm related mortality were observed overall, and in the endovascular era irrespective of age, sex, and rupture status.

Trends in pulmonary tuberculosis mortality between 1985 and 2018: an observational analysis.

BACKGROUND: Pulmonary tuberculosis (TB) is a major source of global morbidity and mortality. Latent infection has enabled it to spread to a quarter of the world's population. The late 1980s and early 1990s saw an increase in the number of TB cases related to the HIV epidemic, and the spread of multidrug-resistant TB. Few studies have reported pulmonary TB mortality trends. Our study reports and compares trends in pulmonary TB mortality. METHODS: We utilized the World Health Organization (WHO) mortality database from 1985 through 2018 to analyze TB mortality using the International Classification of Diseases-10 codes. Based on the availability and quality of data, we investigated 33 countries including two countries from the Americas; 28 countries from Europe; and 3 countries from the Western Pacific region. Mortality rates were dichotomized by sex. We computed age-standardized death rates per 100,000 population using the world standard population. Time trends were investigated using joinpoint regression analysis. RESULTS: We observed a uniform decrease in mortality in all countries across the study period except the Republic of Moldova, which showed an increase in female mortality (+ 0.12 per 100,000 population). Among all countries, Lithuania had the greatest reduction in male mortality (-12) between 1993-2018, and Hungary had the greatest reduction in female mortality (-1.57) between 1985-2017. For males, Slovenia had the most rapid recent declining trend with an estimated annual percentage change (EAPC) of -47% (2003-2016), whereas Croatia showed the fastest increase (EAPC, + 25.0% [2015-2017]). For females, New Zealand had the most rapid declining trend (EAPC, -47.2% [1985-2015]), whereas Croatia showed a rapid increase (EAPC, + 24.9% [2014-2017]). CONCLUSIONS: Pulmonary TB mortality is disproportionately higher among Central and Eastern European countries. This communicable disease cannot be eliminated from any one region without a global approach. Priority action areas include ensuring early diagnosis and successful treatment to the most vulnerable groups such as people of foreign origin from countries with a high burden of TB and incarcerated population. Incomplete reporting of TB-related epidemiological data to WHO excluded high-burden countries and limited our study to 33 countries only. Improvement in reporting is crucial to accurately identify changes in epidemiology, the effect of new treatments, and management approaches.

Trends in Thoracic Aortic Aneurysm Hospital Admissions, Interventions, and Mortality in England between 1998 and 2020: An Observational Study.

OBJECTIVE: To assess trends in thoracic aortic aneurysm (TAA) hospital admissions, interventions, and aneurysm related mortality (ARM) in England, and examine the impact of endovascular repair on mortality for the years 1998 to 2020. METHODS: Hospital admission and operative approach (thoracic endovascular aortic repair, [TEVAR] or open surgical repair) using Hospital Episodes Statistics, and ARM data from the Office for National Statistics for England standardised to the 2013 European Standard Population were analysed using linear regression and Joinpoint regression analyses. ARM was compared between the pre-endovascular era (1998 - 2008) and the endovascular era (2009 - 2019). RESULTS: A rising trend in hospital admission incidence has been observed, mainly due non-ruptured admissions (4.11 per 100 000 in 1998; 95% confidence interval (CI) 3.71 - 4.50 to 12.61 per 100 000 in 2020; 95% CI 12.00 - 13.21 in 2020; r2 = .98; p < .001). Operative interventions increased mainly due to an increase in TEVAR (2.15 per 100 000; 95% CI 1.91 - 2.41 in 2020 vs. 0.26 per 100 000; 95% CI 0.16 - 0.36 in 2006; r2 = .90; p < .001). Reductions in ARM from TAA were observed for males and females, irrespective of age and rupture status. The greatest reduction in ARM in the endovascular era was observed in females aged > 80 years with ruptured disease (15.26 deaths per 100 000 vs. 9.50 deaths per 100 000; p < .001). CONCLUSION: A significant increase in hospital admissions for non-ruptured TAA has been observed in the last 23 years in England, paralleled by a shift towards endovascular repair, and significant declining trends in ARM, irrespective of sex and age. The significant reductions in age standardised death rates from ruptured and non-ruptured TAA in the endovascular era, particularly for females aged > 80 years with ruptured disease, affirm the positive impact of an endovascular approach to TAA.

Trends in prevalence, mortality, and disability-adjusted life-years relating to chronic obstructive pulmonary disease in Europe: an observational study of the global burden of disease database, 2001-2019.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is associated with significant mortality and well-defined aetiological factors. Previous reports indicate that mortality from COPD is falling worldwide. This study aims to assess the burden of COPD using prevalence, mortality, and disability-adjusted life years (DALYs) between 2001 and 2019 in 28 European countries (the European Union and the United Kingdom). METHODS: We extracted COPD data from the Global Burden of Disease database based on the International Classification of Diseases versions 10 (J41, 42, 43, 44 and 47). Age-standardised prevalence rates (ASPRs), age-standardised mortality rates (ASMRs), and DALYs were analysed for European countries by sex for each year (2001-2019) and reported per 100,000 population. We used Joinpoint regression analysis to quantify changing trends in the burden of COPD. RESULTS: In 2019, the median ASPR across Europe was 3230/100,000 for males and 2202/100,000 for females. Between 2001 and 2019, the median percentage change in ASPR was - 9.7% for males and 4.3% for females. 23/28 countries demonstrated a decrease in ASPRs in males, and 11/28 demonstrated a decrease in females. The median percentage change in ASMR between 2001 and 2019 was - 27.5% for males and - 10.4% for females. 25/28 and 19/28 countries demonstrated a decrease in ASMR in males and females, respectively. CONCLUSION: In the EU between 2001 and 2019 COPD prevalence has overall increased in females but continues to decrease in males and in some countries, female prevalence now exceeds that of males. COPD mortality in the EU has decreased overall between 2001 and 2019; however, this decrease is not universal, particularly in females, and therefore remains a substantial source of amenable mortality.

Paradoxical impact of socioeconomic factors on outcome of atrial fibrillation in Europe: trends in incidence and mortality from atrial fibrillation.

AIMS: The aim of this study was to understand the changing trends in atrial fibrillation (AF) incidence and mortality across Europe from 1990 to 2017, and how socioeconomic factors and sex differences play a role. METHODS AND RESULTS: We performed a temporal analysis of data from the 2017 Global Burden of Disease Database for 20 countries across Europe using Joinpoint regression analysis. Age-adjusted incidence, mortality, and mortality-to-incidence ratios (MIRs) to approximate case fatality rate are presented. Incidence and mortality trends were heterogenous throughout Europe, with Austria, Denmark, and Sweden experiencing peaks in incidence in the middle of the study period. Mortality rates were higher in wealthier countries with the highest being Sweden for both men and women (8.83 and 8.88 per 100 000, respectively) in 2017. MIRs were higher in women in all countries studied, with the disparity increasing the most over time in Germany (43.6% higher in women vs. men in 1990 to 74.5% higher in women in 2017). CONCLUSION: AF incidence and mortality across Europe did not show a general trend, but unique patterns for some nations were observed. Higher mortality rates were observed in wealthier countries, potentially secondary to a survivor effect where patients survive long enough to suffer from AF and its complications. Outcomes for women with AF were worse than men, represented by higher MIRs. This suggests that there is widespread healthcare inequality between the sexes across Europe, or that there are biological differences between them in terms of their risk of adverse outcomes from AF.

An observational epidemiological study to analyze intracerebral hemorrhage across the United States: Incidence and mortality trends from 1990 to 2017.

OBJECTIVES: Intracerebral Hemorrhage (ICH) accounts for 10% of strokes annually in the United States (US). Up-to-date trends in disease burden and regional variations remain unknown. Our study reports updated trends of ICH incidence, mortality, and mortality to incidence ratio (MIR) across the US. MATERIALS AND METHODS: Observational study to evaluate the incidence and mortality from ICH across the US. Data was obtained from Global Burden of Disease (GBD) database. Age-Standardized Incidence (ASIRs) and Death (ASDRs) Rates, as well as the Mortality- to-Incidence ratios (MIRs) for ICH in the US overall and state-wise from 1990-2017. Joinpoint regression analysis was used, with presentation of estimated annual percentage changes (EAPCs). RESULTS: Overall decrease in ASIRs, ASDRs, and MIRs in the US for both sexes. The 2017 mean ASIR was 25.67/100,000 for men and 19.17/100,000 for women, whereas mean ASDR was 13.96/100,000 for men and 11.35/100,000 for women. District of Columbia had greatest decreases in ASIR EAPCs for both men and women at -41.25% and -40.58%, respectively, and greatest decreases in ASDR EAPCs for men and women at -55.38% and -48.51%, respectively. MIR between 1990-2017 decreased in men by -12.12% and women by -7.43%. MIR increased in men from 2014-2017 (EAPC +2.2%) and in women from 2011-2017 (EAPC +1.0%). CONCLUSION: Decreasing trends in incidence, mortality, and MIR. No significant trends in mortality were found in the last 6 years of the study period. MIR worsened in males from 2014-2017 and females from 2011-2017, suggesting decreased ICH-related survival lately.

Socioeconomic Factors Associated With Liver-Related Mortality From 1985 to 2015 in 36 Developed Countries.

BACKGROUND & AIMS: There is increasing disparity in liver-related mortality worldwide. Although there are many biologic and lifestyle risk factors for liver-related mortality, the effects of inequalities in social and economic determinants of health have received little attention. We investigated changes in liver-related mortality from 1985 through 2015 in 36 countries, using 4 international health and economic databases, and searched for socioeconomic factors that might influence these trends. METHODS: We collected information on sex- and country-specific liver-related mortality from countries with designated high-usability data from the World Health Organization mortality database. We obtained data on alcohol consumption per capita, the percentage of adults with a body mass index greater than 30 kg/m2, health expenditure per capita, gross domestic product per capita, Gini index, national unemployment estimates, and diabetes prevalence from the World Health Organization global health observatory data repository, the World Bank database, and the International Diabetes Federation. We examined changes in mortality using Joinpoint regression analysis. Univariate analysis and a mixed-effects linear model were used to identify factors associated with liver-related mortality. RESULTS: From 1985 to 2015, the mean liver-related deaths per 100,000 persons increased in men from 23.8 to 26.1, and in women from 9.7 to 11.9. Increased liver-related mortality was associated with male sex, a high level of alcohol consumption, obesity, and indicators of national wealth and government health expenditure gross domestic product or government expenditure on health. CONCLUSIONS: In addition to established risk factors for liver mortality, this study identified addressable economic factors associated with liver-related mortality trends. Health care professionals and policy makers may wish to consider these factors to reduce liver-related mortality.

Maximum Daily Temperature, Precipitation, Ultraviolet Light, and Rates of Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in the United States.

BACKGROUND: Previous reports have suggested that transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is reduced by higher temperatures and higher humidity. We analyzed case data from the United States to investigate the effects of temperature, precipitation, and ultraviolet (UV) light on community transmission of SARS-CoV-2. METHODS: Daily reported cases of SARS-CoV-2 across the United States from 22 January 2020 to 3 April 2020 were analyzed. We used negative binomial regression modeling to determine whether daily maximum temperature, precipitation, UV index, and the incidence 5 days later were related. RESULTS: A maximum temperature above 52°F on a given day was associated with a lower rate of new cases at 5 days (incidence rate ratio [IRR], 0.85 [0.76, 0.96]; P = .009). Among observations with daily temperatures below 52°F, there was a significant inverse association between the maximum daily temperature and the rate of cases at 5 days (IRR, 0.98 [0.97, 0.99]; P = .001). A 1-unit higher UV index was associated with a lower rate at 5 days (IRR, 0.97 [0.95, 0.99]; P = .004). Precipitation was not associated with a greater rate of cases at 5 days (IRR, 0.98 [0.89, 1.08]; P = .65). CONCLUSIONS: The incidence of disease declines with increasing temperature up to 52°F and is lower at warmer vs cooler temperatures. However, the association between temperature and transmission is small, and transmission is likely to remain high at warmer temperatures.

Editor's Choice - Trends in Lower Extremity Amputation Incidence in European Union 15+ Countries 1990-2017.

OBJECTIVE: Lower extremity amputation (LEA) carries significant mortality, morbidity, and health economic burden. In the Western world, it most commonly results from complications of peripheral arterial occlusive disease (PAOD) or diabetic foot disease. The incidence of PAOD has declined in Europe, the United States, and parts of Australasia. The present study aimed to assess trends in LEA incidence in European Union (EU15+) countries for the years 1990-2017. METHODS: This was an observational study using data obtained from the 2017 Global Burden of Disease (GBD) Study. Age standardised incidence rates (ASIRs) for LEA (stratified into toe amputation, and LEA proximal to toes) were extracted from the GBD Results Tool (http://ghdx.healthdata.org/gbd-results-tool) for EU15+ countries for each of the years 1990-2017. Trends were analysed using Joinpoint regression analysis. RESULTS: Between 1990 and 2017, variable trends in the incidence of LEA were observed in EU15+ countries. For LEAs proximal to toes, increasing trends were observed in six of 19 countries and decreasing trends in nine of 19 countries, with four countries showing varying trends between sexes. For toe amputation, increasing trends were observed in eight of 19 countries and decreasing trends in eight of 19 countries for both sexes, with three countries showing varying trends between sexes. Australia had the highest ASIRs for both sexes in all LEAs at all time points, with steadily increasing trends. The USA observed the greatest reduction in all LEAs in both sexes over the time period analysed (LEAs proximal to toes: female patients -22.93%, male patients -29.76%; toe amputation: female patients -29.93%, male patients -32.67%). The greatest overall increase in incidence was observed in Australia. CONCLUSION: Variable trends in LEA incidence were observed across EU15+ countries. These trends do not reflect previously observed reductions in incidence of PAOD over the same time period.

Trends in mortality from idiopathic pulmonary fibrosis in the European Union: an observational study of the WHO mortality database from 2001-2013.

Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic interstitial pneumonias and is characterised by progressive accumulation of scar tissue in the lungs. The objective of this study was to describe the current mortality rates due to IPF in Europe, based on the World Health Organization (WHO) mortality database.We used country-level data for IPF mortality, identified in the WHO mortality database using International Classification of Diseases 10th Edition (ICD-10) codes, for the period 2001-2013. Joinpoint analysis was performed to describe trends throughout the observation period.The median mortality was 3.75 per 100 000 (interquartile range (IQR) 1.37-5.30) and 1.50 per 100 000 (IQR 0.65-2.02) for males and females, respectively. IPF mortality increased in the majority of the European Union (EU) countries with the exceptions of Denmark, Croatia, Austria and Romania. There was a significant disparity in rates across Europe, in the range 0.41-12.1 per 100 000 for men and 0.24-5.63 per 100 000 for women. The most notable increases were observed in the United Kingdom and Finland. Rates were also substantially higher in males, with sex disparity increasing across the period.The reported IPF mortality appears to be increasing across the EU; however, there is substantial variation in mortality trends and overall reported mortality rates between countries.

Trends in mortality from pneumonia in the Europe union: a temporal analysis of the European detailed mortality database between 2001 and 2014.

BACKGROUND: Pneumonia is responsible for approximately 230,000 deaths in Europe, annually. Comprehensive and comparable reports on pneumonia mortality trends across the European Union (EU) are lacking. METHODS: A temporal analysis of national mortality statistics to compare trends in pneumonia age-standardised death rates (ASDR) of EU countries between 2001 and 2014 was performed. International Classification of Diseases version 10 (ICD-10) codes were used to extract data from the World Health Organisation European Detailed Mortality Database and trends were analysed using Joinpoint regression. RESULTS: Median pneumonia mortality across the EU for the last recorded observation was 19.8 / 100,000 and 6.9 / 100,000 for males and females, respectively. Mortality was higher in males across all EU countries, most notably in Estonia and Lithuania where the ratio of male to female ASDR was 4.0 and 3.7, respectively. Gender mortality differences were lowest in the UK and Demark with ASDR ratios of 1.1 and 1.5, respectively. Pneumonia mortality across all countries decreased by a median of 31.0% over the observation period. Countries that demonstrated an increase in pneumonia mortality were Poland (males + 33.1%, females + 10.2%), and Lithuania (males + 6.0%). CONCLUSIONS: Mortality from pneumonia is improving in most EU countries, however substantial variation in trends remains between countries and between genders.

Trends in Mortality From Ischemic Heart Disease and Cerebrovascular Disease in Europe: 1980 to 2009.

BACKGROUND: Trends in cardiovascular mortality across Europe demonstrate significant geographical variation, and an understanding of these trends has a central role in global public health. METHODS AND RESULTS: Ischemic heart disease and cerebrovascular disease age-standardized death rates (as per International Classification of Diseases, ninth and tenth revisions) were collated from the World Health Organization mortality database for member states of the European Union. Trends were characterized by using Joinpoint regression analysis. An overall trend for reduction in ischemic heart disease mortality was observed, most pronounced in Western Europe (>60% for the Netherlands, United Kingdom, and Ireland) for both sexes from 1980 to 2009. Eastern European states, Romania, Croatia, and Slovakia, had modest mortality reductions. Most recently (2009), Lithuania had the highest mortality for males and females (318.1/100 000 and 166.1/100 000, respectively), followed by Latvia and Slovakia. France had the lowest mortality: 39.8/100 000 for males and 14.7/100 000 for females. Analysis of cerebrovascular disease mortality revealed that Austria had the largest reduction for both sexes (76.8% males, 76.5% females) from 1980 to 2009. The smallest improvement over this period was seen in Lithuania, Poland, and Cyprus (-5% to +20% approximately). France has the lowest present-day cerebrovascular disease mortality for both males and females (23.9/100 000 and 17.3/100 000, respectively). CONCLUSIONS: There is a growing disparity in cardiovascular mortality between Western and Eastern Europe, for which diverse explanations are discussed. The need for population-wide health promotion and primary prevention policies is emphasized.

Trends in UK regional cancer mortality 1991-2007.

BACKGROUND: Until 1990, there was an upward trend in mortality from breast, lung, prostate, and colon cancers in the United Kingdom. With improvements in cancer treatment there has, in general, been a fall in mortality over the last 20 years. We evaluate regional cancer mortality trends in the United Kingdom between 1991 and 2007. METHODS: We analysed mortality trends for breast, lung, prostate, and colon cancers using data obtained from the EUREG cancer database. We have described changes in age-standardised rates (using European standard population) per 100,000 for cancer mortality and generated trends in mortality for the 11 regions using Joinpoint regression. RESULTS: Across all regions in the United Kingdom there was a downward trend in mortality for the four most common cancers in males and females. Overall, deaths from colon cancer decreased most rapidly and deaths from prostate cancer decreased at the slowest rate. Similar downward trends in mortality were observed across all regions of the United Kingdom with the data for lung cancer exhibiting the greatest variation. CONCLUSIONS: Mortality from the four most common cancers decreased across all regions of the United Kingdom; however, the rate of decline varied between cancer type and in some instances by region.

Bridging the Health Data Divide.

Fundamental quality, safety, and cost problems have not been resolved by the increasing digitization of health care. This digitization has progressed alongside the presence of a persistent divide between clinicians, the domain experts, and the technical experts, such as data scientists. The disconnect between clinicians and data scientists translates into a waste of research and health care resources, slow uptake of innovations, and poorer outcomes than are desirable and achievable. The divide can be narrowed by creating a culture of collaboration between these two disciplines, exemplified by events such as datathons. However, in order to more fully and meaningfully bridge the divide, the infrastructure of medical education, publication, and funding processes must evolve to support and enhance a learning health care system.

The 2015 advanced life support guidelines: a summary and evidence for the updates.

The International Liaison Committee on Resuscitation recently released updated 2015 recommendations for resuscitation. The guidelines form the basis for all levels of resuscitation training, now from first aid to advanced life support (ALS), and for trainees of varying medical skills, from schoolchildren to medical students and consultants. We highlight major updates relating to intra-arrest and postarrest care, and the evidence for their recommendation. We also summarise areas of uncertainty in the evidence for ALS, and highlight current discussions that will likely inform the next round of recommendations.

The association between the neutrophil-to-lymphocyte ratio and mortality in critical illness: an observational cohort study.

INTRODUCTION: The neutrophil-to-lymphocyte ratio (NLR) is a biological marker that has been shown to be associated with outcomes in patients with a number of different malignancies. The objective of this study was to assess the relationship between NLR and mortality in a population of adult critically ill patients. METHODS: We performed an observational cohort study of unselected intensive care unit (ICU) patients based on records in a large clinical database. We computed individual patient NLR and categorized patients by quartile of this ratio. The association of NLR quartiles and 28-day mortality was assessed using multivariable logistic regression. Secondary outcomes included mortality in the ICU, in-hospital mortality and 1-year mortality. An a priori subgroup analysis of patients with versus without sepsis was performed to assess any differences in the relationship between the NLR and outcomes in these cohorts. RESULTS: A total of 5,056 patients were included. Their 28-day mortality rate was 19%. The median age of the cohort was 65 years, and 47% were female. The median NLR for the entire cohort was 8.9 (interquartile range, 4.99 to 16.21). Following multivariable adjustments, there was a stepwise increase in mortality with increasing quartiles of NLR (first quartile: reference category; second quartile odds ratio (OR) = 1.32; 95% confidence interval (CI), 1.03 to 1.71; third quartile OR = 1.43; 95% CI, 1.12 to 1.83; 4th quartile OR = 1.71; 95% CI, 1.35 to 2.16). A similar stepwise relationship was identified in the subgroup of patients who presented without sepsis. The NLR was not associated with 28-day mortality in patients with sepsis. Increasing quartile of NLR was statistically significantly associated with secondary outcome. CONCLUSION: The NLR is associated with outcomes in unselected critically ill patients. In patients with sepsis, there was no statistically significant relationship between NLR and mortality. Further investigation is required to increase understanding of the pathophysiology of this relationship and to validate these findings with data collected prospectively.