Antimicrobial use in European acute care hospitals: results from the second point prevalence survey (PPS) of healthcare-associated infections and antimicrobial use, 2016 to 2017

Antimicrobial agents used to treat infections are life-saving. Overuse may result in more frequent adverse effects and emergence of multidrug-resistant microorganisms. In 2016-17, we performed the second point-prevalence survey (PPS) of healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals. We included 1,209 hospitals and 310,755 patients in 28 of 31 European Union/European Economic Area (EU/EEA) countries. The weighted prevalence of antimicrobial use in the EU/EEA was 30.5% (95% CI: 29.2-31.9%). The most common indication for prescribing antimicrobials was treatment of a community-acquired infection, followed by treatment of HAI and surgical prophylaxis. Over half (54.2%) of antimicrobials for surgical prophylaxis were prescribed for more than 1 day. The most common infections treated by antimicrobials were respiratory tract infections and the most commonly prescribed antimicrobial agents were penicillins with beta-lactamase inhibitors. There was wide variation of patients on antimicrobials, in the selection of antimicrobial agents and in antimicrobial stewardship resources and activities across the participating countries. The results of the PPS provide detailed information on antimicrobial use in European acute care hospitals, enable comparisons between countries and hospitals, and highlight key areas for national and European action that will support efforts towards prudent use of antimicrobials

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Trans-ancestral genome-wide association study of longitudinal pubertal height growth and shared heritability with adult health outcomes

Background: Pubertal growth patterns correlate with future health outcomes. However, the genetic mechanisms mediating growth trajectories remain largely unknown. Here, we modeled longitudinal height growth with Super-Imposition by Translation And Rotation (SITAR) growth curve analysis on ~ 56,000 trans-ancestry samples with repeated height measurements from age 5 years to adulthood. We performed genetic analysis on six phenotypes representing the magnitude, timing, and intensity of the pubertal growth spurt. To investigate the lifelong impact of genetic variants associated with pubertal growth trajectories, we performed genetic correlation analyses and phenome-wide association studies in the Penn Medicine BioBank and the UK Biobank. Results: Large-scale growth modeling enables an unprecedented view of adolescent growth across contemporary and 20th-century pediatric cohorts. We identify 26 genome-wide significant loci and leverage trans-ancestry data to perform fine-mapping. Our data reveals genetic relationships between pediatric height growth and health across the life course, with different growth trajectories correlated with different outcomes. For instance, a faster tempo of pubertal growth correlates with higher bone mineral density, HOMA-IR, fasting insulin, type 2 diabetes, and lung cancer, whereas being taller at early puberty, taller across puberty, and having quicker pubertal growth were associated with higher risk for atrial fibrillation. Conclusion: We report novel genetic associations with the tempo of pubertal growth and find that genetic determinants of growth are correlated with reproductive, glycemic, respiratory, and cardiac traits in adulthood. These results aid in identifying specific growth trajectories impacting lifelong health and show that there may not be a single “optimal” pubertal growth pattern

Meeting the International Health Regulations (2005) surveillance core capacity requirements at the subnational level in Europe: the added value of syndromic surveillance

BACKGROUND: The revised World Health Organization's International Health Regulations (2005) request a timely and all-hazard approach towards surveillance, especially at the subnational level. We discuss three questions of syndromic surveillance application in the European context for assessing public health emergencies of international concern: (i) can syndromic surveillance support countries, especially the subnational level, to meet the International Health Regulations (2005) core surveillance capacity requirements, (ii) are European syndromic surveillance systems comparable to enable cross-border surveillance, and (iii) at which administrative level should syndromic surveillance best be applied? DISCUSSION: Despite the ongoing criticism on the usefulness of syndromic surveillance which is related to its clinically nonspecific output, we demonstrate that it was a suitable supplement for timely assessment of the impact of three different public health emergencies affecting Europe. Subnational syndromic surveillance analysis in some cases proved to be of advantage for detecting an event earlier compared to national level analysis. However, in many cases, syndromic surveillance did not detect local events with only a small number of cases. The European Commission envisions comparability of surveillance output to enable cross-border surveillance. Evaluated against European infectious disease case definitions, syndromic surveillance can contribute to identify cases that might fulfil the clinical case definition but the approach is too unspecific to comply to complete clinical definitions. Syndromic surveillance results still seem feasible for comparable cross-border surveillance as similarly defined syndromes are analysed. We suggest a new model of implementing syndromic surveillance at the subnational level. In this model, syndromic surveillance systems are fine-tuned to their local context and integrated into the existing subnational surveillance and reporting structure. By enhancing population coverage, events covering several jurisdictions can be identified at higher levels. However, the setup of decentralised and locally adjusted syndromic surveillance systems is more complex compared to the setup of one national or local system. SUMMARY: We conclude that syndromic surveillance if implemented with large population coverage at the subnational level can help detect and assess the local and regional effect of different types of public health emergencies in a timely manner as required by the International Health Regulations (2005)

The potential risks and impact of the start of the 2015–2016 influenza season in the WHO European Region: a rapid risk assessment

Background: Countries in the World Health Organization (WHO) European Region are reporting more severe influenza activity in the 2015–2016 season compared to previous seasons. Objectives: To conduct a rapid risk assessment to provide interim information on the severity of the current influenza season. Methods: Using the WHO manual for rapid risk assessment of acute public health events and surveillance data available from Flu News Europe, an assessment of the current influenza season from 28 September 2015 (week 40/2015) up to 31 January 2016 (week 04/2016) was made compared with the four previous seasons. Results: The current influenza season started around week 51/2015 with higher influenza activity reported in Eastern Europe compared to Western Europe. There is a strong predominance of influenza A(H1N1)pdm09 compared to previous seasons, but the virus is antigenically similar to the strain included in the seasonal influenza vaccine. Compared to the 2014/2015 season, there was a rapid increase in the number of severe cases in Eastern European countries with the majority of such cases occurring among adults aged < 65 years. Conclusions: The current influenza season is characterized by an early start in Eastern European countries, with indications of a more severe season. Currently circulating influenza A(H1N1)pdm09 viruses are antigenically similar to those included in the seasonal influenza vaccine, and the vaccine is expected to be effective. Authorities should provide information to the public and health providers about the current influenza season, recommendations for the treatment of severe disease and effective public health measures to prevent influenza transmission

Mendelian Randomization Studies Do Not Support a Causal Role for Reduced Circulating Adiponectin Levels in Insulin Resistance and Type 2 Diabetes

Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics–based genetic risk scores to test the associations with gold-standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 case subjects and 64,731 control subjects). In conventional regression analyses, a 1-SD decrease in adiponectin levels was correlated with a 0.31-SD (95% CI 0.26–0.35) increase in fasting insulin, a 0.34-SD (0.30–0.38) decrease in insulin sensitivity, and a type 2 diabetes odds ratio (OR) of 1.75 (1.47–2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD; 95% CI −0.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (−0.20 SD; 95% CI −0.38 to −0.02; N = 1,860), and no evidence of a relationship with type 2 diabetes (OR 0.94; 95% CI 0.75–1.19; N = 2,777 case subjects and 13,011 control subjects). Using the ADIPOQ summary statistics genetic risk scores, we found no evidence of an association between adiponectin-lowering alleles and insulin sensitivity (effect per weighted adiponectin-lowering allele: −0.03 SD; 95% CI −0.07 to 0.01; N = 2,969) or type 2 diabetes (OR per weighted adiponectin-lowering allele: 0.99; 95% CI 0.95–1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of type 2 diabetes

Association of Chromosome 9p21 with Subsequent Coronary Heart Disease events:A GENIUS-CHD study of individual participant data

BACKGROUND:Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS:A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103,357 Europeans with established CHD at baseline from the GENIUS-CHD Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/MI), occurred in 13,040 of the 93,115 participants with available outcome data. Effect estimates were compared to case/control risk obtained from CARDIoGRAMPlusC4D including 47,222 CHD cases and 122,264 controls free of CHD. RESULTS:Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/MI among those with established CHD at baseline (GENIUS-CHD OR 1.02; 95% CI 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D OR 1.20; 95% CI 1.18-1.22; p for interaction Conclusions: In contrast to studies comparing individuals with CHD to disease free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development