Trends in type 2 diabetes mellitus disease burden in European Union countries between 1990 and 2019.

This observational study aimed to assess trends in type 2 diabetes mellitus (T2DM) disease burden in European Union countries for the years 1990-2019. Sex specific T2DM age-standardised prevalence (ASPRs), mortality (ASMRs) and disability-adjusted life-year rates (DALYs) per 100,000 population were extracted from the Global Burden of Disease (GBD) Study online results tool for each EU country (inclusive of the United Kingdom), for the years 1990-2019. Trends were analysed using Joinpoint regression analysis. Between 1990 and 2019, increases in T2DM ASPRs were observed for all EU countries. The highest relative increases in ASPRs were observed in Luxembourg (males + 269.1%, females + 219.2%), Ireland (males + 191.9%, females + 165.7%) and the UK (males + 128.6%, females + 114.6%). Mortality trends were less uniform across EU countries, however a general trend towards reducing T2DM mortality was observed, with ASMRs decreasing over the 30-year period studied in 16/28 countries for males and in 24/28 countries for females. The UK observed the highest relative decrease in ASMRs for males (- 46.9%). For females, the largest relative decrease in ASMRs was in Cyprus (- 67.6%). DALYs increased in 25/28 countries for males and in 17/28 countries for females between 1990 and 2019. DALYs were higher in males than females in all EU countries in 2019. T2DM prevalence rates have increased across EU countries over the last 30 years. Mortality from T2DM has generally decreased in EU countries, however trends were more variable than those observed for prevalence. Primary prevention strategies should continue to be a focus for preventing T2DM in at risk groups in EU countries

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.National Institutes of Health (U.S.) (Grant R01 EB017205-01A1

Association between Inflammation and Cardiac Geometry in Chronic Kidney Disease: Findings from the CRIC Study.

Background Left ventricular hypertrophy (LVH) and myocardial contractile dysfunction are independent predictors of mortality in patients with chronic kidney disease (CKD). The association between inflammatory biomarkers and cardiac geometry has not yet been studied in a large cohort of CKD patients with a wide range of kidney function. Methods Plasma levels of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, high-sensitivity C-Reactive protein (hs-CRP), fibrinogen and serum albumin were measured in 3,939 Chronic Renal Insufficiency Cohort study participants. Echocardiography was performed according to the recommendations of the American Society of Echocardiography and interpreted at a centralized core laboratory. Results LVH, systolic dysfunction and diastolic dysfunction were present in 52.3%, 11.8% and 76.3% of the study subjects, respectively. In logistic regression analysis adjusted for age, sex, race/ethnicity, diabetic status, current smoking status, systolic blood pressure, urinary albumin- creatinine ratio and estimated glomerular filtration rate, hs-CRP (OR 1.26 [95% CI 1.16, 1.37], p Conclusion In patients with CKD, elevated plasma levels of hs-CRP and IL-6 are associated with LVH and systolic dysfunction

Effects of health and social care spending constraints on mortality in England: a time trend analysis.

OBJECTIVE: Since 2010, England has experienced relative constraints in public expenditure on healthcare (PEH) and social care (PES). We sought to determine whether these constraints have affected mortality rates. METHODS: We collected data on health and social care resources and finances for England from 2001 to 2014. Time trend analyses were conducted to compare the actual mortality rates in 2011-2014 with the counterfactual rates expected based on trends before spending constraints. Fixed-effects regression analyses were conducted using annual data on PES and PEH with mortality as the outcome, with further adjustments for macroeconomic factors and resources. Analyses were stratified by age group, place of death and lower-tier local authority (n=325). Mortality rates to 2020 were projected based on recent trends. RESULTS: Spending constraints between 2010 and 2014 were associated with an estimated 45 368 (95% CI 34 530 to 56 206) higher than expected number of deaths compared with pre-2010 trends. Deaths in those aged ≥60 and in care homes accounted for the majority. PES was more strongly linked with care home and home mortality than PEH, with each £10 per capita decline in real PES associated with an increase of 5.10 (3.65-6.54) (p<0.001) care home deaths per 100 000. These associations persisted in lag analyses and after adjustment for macroeconomic factors. Furthermore, we found that changes in real PES per capita may be linked to mortality mostly via changes in nurse numbers. Projections to 2020 based on 2009-2014 trend was cumulatively linked to an estimated 152 141 (95% CI 134 597 and 169 685) additional deaths. CONCLUSIONS: Spending constraints, especially PES, are associated with a substantial mortality gap. We suggest that spending should be targeted on improving care delivered in care homes and at home; and maintaining or increasing nurse numbers

An O-Antigen glycoconjugate vaccine produced using protein glycan coupling technology is protective in an inhalational rat model of tularemia

There is a requirement for an efficacious vaccine to protect people against infection from Francisella tularensis, the etiological agent of tularemia. The lipopolysaccharide (LPS) of F. tularensis is suboptimally protective against a parenteral lethal challenge in mice. To develop a more efficacious subunit vaccine, we have used a novel biosynthetic technique of protein glycan coupling technology (PGCT) that exploits bacterial N-linked glycosylation to recombinantly conjugate F. tularensis O-antigen glycans to the immunogenic carrier protein Pseudomonas aeruginosa exoprotein A (ExoA). Previously, we demonstrated that an ExoA glycoconjugate with two glycosylation sequons was capable of providing significant protection to mice against a challenge with a low-virulence strain of F. tularensis. Here, we have generated a more heavily glycosylated conjugate vaccine and evaluated its efficacy in a Fischer 344 rat model of tularemia. We demonstrate that this glycoconjugate vaccine protected rats against disease and the lethality of an inhalational challenge with F. tularensis Schu S4. Our data highlights the potential of this biosynthetic approach for the creation of next-generation tularemia subunit vaccines

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

The Seroepidemiology of Haemophilus influenzae Type B Prior to Introduction of an Immunization Programme in Kathmandu, Nepal.

Haemophilus influenzae type b (Hib) is now recognized as an important pathogen in Asia. To evaluate disease susceptibility, and as a marker of Hib transmission before routine immunization was introduced in Kathmandu, 71 participants aged 7 months-77 years were recruited and 15 cord blood samples were collected for analysis of anti-polyribosylribitol phosphate antibody levels by enzyme-linked immunosorbent assay. Only 20% of children under 5 years old had levels considered protective (>0.15 µg/ml), rising to 83% of 15-54 year-olds. Prior to introduction of Hib vaccine in Kathmandu, the majority of young children were susceptible to disease

Rationale and design of a longitudinal study of cerebral small vessel diseases, clinical and imaging outcomes in patients presenting with mild ischaemic stroke: Mild Stroke Study 3

Background: Cerebral small vessel disease is a major cause of dementia and stroke, visible on brain magnetic resonance imaging. Recent data suggest that small vessel disease lesions may be dynamic, damage extends into normal-appearing brain and microvascular dysfunctions include abnormal blood–brain barrier leakage, vasoreactivity and pulsatility, but much remains unknown regarding underlying pathophysiology, symptoms, clinical features and risk factors of small vessel disease. Patients and Methods: The Mild Stroke Study 3 is a prospective observational cohort study to identify risk factors for and clinical implications of small vessel disease progression and regression among up to 300 adults with non-disabling stroke. We perform detailed serial clinical, cognitive, lifestyle, physiological, retinal and brain magnetic resonance imaging assessments over one year; we assess cerebrovascular reactivity, blood flow, pulsatility and blood–brain barrier leakage on magnetic resonance imaging at baseline; we follow up to four years by post and phone. The study is registered ISRCTN 12113543. Summary: Factors which influence direction and rate of change of small vessel disease lesions are poorly understood. We investigate the role of small vessel dysfunction using advanced serial neuroimaging in a deeply phenotyped cohort to increase understanding of the natural history of small vessel disease, identify those at highest risk of early disease progression or regression and uncover novel targets for small vessel disease prevention and therapy