Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: a population-level modelling analysis

Background: Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Area (EEA) in 2015, measured in number of cases, attributable deaths, and disability-adjusted life-years (DALYs). Methods: We estimated the incidence of infections with 16 antibiotic resistance–bacterium combinations from European Antimicrobial Resistance Surveillance Network (EARS-Net) 2015 data that was country-corrected for population coverage. We multiplied the number of bloodstream infections (BSIs) by a conversion factor derived from the European Centre for Disease Prevention and Control point prevalence survey of health-care-associated infections in European acute care hospitals in 2011–12 to estimate the number of non-BSIs. We developed disease outcome models for five types of infection on the basis of systematic reviews of the literature. Findings: From EARS-Net data collected between Jan 1, 2015, and Dec 31, 2015, we estimated 671 689 (95% uncertainty interval [UI] 583 148–763 966) infections with antibiotic-resistant bacteria, of which 63·5% (426 277 of 671 689) were associated with health care. These infections accounted for an estimated 33 110 (28 480–38 430) attributable deaths and 874 541 (768 837–989 068) DALYs. The burden for the EU and EEA was highest in infants (aged <1 year) and people aged 65 years or older, had increased since 2007, and was highest in Italy and Greece. Interpretation: Our results present the health burden of five types of infection with antibiotic-resistant bacteria expressed, for the first time, in DALYs. The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007. Our burden estimates provide useful information for public health decision-makers prioritising interventions for infectious diseases

Biological brain age prediction using machine learning on structural neuroimaging data: Multi-cohort validation against biomarkers of Alzheimer's disease and neurodegeneration stratified by sex

Brain-age can be inferred from structural neuroimaging and compared to chronological age (brain-age delta) as a marker of biological brain aging. Accelerated aging has been found in neurodegenerative disorders like Alzheimer's disease (AD), but its validation against markers of neurodegeneration and AD is lacking. Here, imaging-derived measures from the UK Biobank dataset (N=22,661) were used to predict brain-age in 2,314 cognitively unimpaired (CU) individuals at higher risk of AD and mild cognitive impaired (MCI) patients from four independent cohorts with available biomarker data: ALFA+, ADNI, EPAD, and OASIS. Brain-age delta was associated with abnormal amyloid-β, more advanced stages (AT) of AD pathology and APOE-ε4 status. Brain-age delta was positively associated with plasma neurofilament light, a marker of neurodegeneration, and sex differences in the brain effects of this marker were found. These results validate brain-age delta as a non-invasive marker of biological brain aging in non-demented individuals with abnormal levels of biomarkers of AD and axonal injury

GUIDELINES FOR GENETIC COUNSELLING AND TESTING FOR HEREDITARY BREAST AND OVARIAN CANCER

Tijekom posljednjih desetljeća svjedoci smo velikog napretka u izvedivosti i kliničkoj iskoristivosti genetičkog testiranja kod nasljednih karcinoma. Nasljedni karcinomi dojke i jajnika najčešće su posljedica mutacija u genima BRCA1 i BRCA2. Ovim smjernicama obuhvatili smo kriterije za upućivanje pacijenata na genetičko savjetovanje i testiranje; kriterije za upućivanje zdravih pojedinaca na prediktivno testiranje ako nije moguće testiranje oboljelog člana obitelji; postupak genetičkog savjetovanja prije i nakon testiranja; nalaz testiranja, kategorije nalaza i razine rizika; preporuke za daljnje praćenje osoba s povišenim rizikom; kemoprevenciju i profilaktičku kirurgiju kod nositelja/-ica patogenih mutacija gena BRCA 1 i BRCA 2; očuvanje reproduktivne funkcije u žena oboljelih od raka dojke i nositeljica mutacija BRCA i pristanak informiranog bolesnika na genetičko testiranje. Smjernice su namijenjene svim specijalistima koji su na bilo koji način uključeni u zbrinjavanje oboljelih od nasljednih karcinoma dojke i jajnika, a sastavila ih je radna skupina prema podacima iz relevantne medicinske literature te kliničkim iskustvima članova radne skupine.The last few decades have witnessed a great progress in feasibility and clinical utilization of genetic testing for hereditary cancers. Hereditary breast and ovarian cancers are most often the result of BRCA1 and BRCA2 gene mutations. In these guidelines we have covered: the criteria for referral of patients to genetic counselling and testing; the criteria for referral of healthy family members to predictive testing in the event when there is no possibility of testing the patient; the process of genetic counselling before and after testing; test results, their categories and risk levels; recommendations for monitoring of individuals with an increased risk; chemoprevention and prophylactic surgery for carriers of BRCA1 and BRCA2 gene mutations; preservation of reproductive function in women with breast cancer and in carriers of BRCA mutations; and informed consent for genetic testing. The guidelines are intended for all specialists who are in any way involved in the care of patients with hereditary breast and ovarian cancer, and are compiled by the working group according to the data from the relevant medical literature and from clinical experience of the members of the working group

Smjernice za genetičko savjetovanje i testiranje na nasljedni rak dojke i jajnika [Guidelines for genetic counselling and testing for hereditary breast and ovarian cancer]

The last few decades have witnessed a great progress in feasibility and clinical utilization of genetic testing for hereditary cancers. Hereditary breast and ovarian cancers are most often the result of BRCA1 and BRCA2 gene mutations. In these guidelines we have covered: the criteria for referral of patients to genetic counselling and testing; the criteria for referral of healthy family members to predictive testing in the event when there is no possibility of testing the patient; the process of genetic counselling before and after testing; test results, their categories and risk levels; recommendations for monitoring of individuals with an increased risk; chemoprevention and prophylactic surgery for carriers of BRCA1 and BRCA2 gene mutations; preservation of reproductive function in women with breast cancer and in carriers of BRCA mutations; and informed consent for genetic testing. The guidelines are intended for all specialists who are in any way involved in the care of patients with hereditary breast and ovarian cancer, and are compiled by the working group according to the data from the relevant medical literature and from clinical experience of the members of the working group

Tele-education model for primary care providers to advance diabetes equity: Findings from Project ECHO Diabetes

IntroductionIn the US, many individuals with diabetes do not have consistent access to endocrinologists and therefore rely on primary care providers (PCPs) for their diabetes management. Project ECHO (Extension for Community Healthcare Outcomes) Diabetes, a tele-education model, was developed to empower PCPs to independently manage diabetes, including education on diabetes technology initiation and use, to bridge disparities in diabetes.MethodsPCPs (n=116) who participated in Project ECHO Diabetes and completed pre- and post-intervention surveys were included in this analysis. The survey was administered in California and Florida to participating PCPs via REDCap and paper surveys. This survey aimed to evaluate practice demographics, protocols with adult and pediatric T1D management, challenges, resources, and provider knowledge and confidence in diabetes management. Differences and statistical significance in pre- and post-intervention responses were evaluated via McNemar’s tests.ResultsPCPs reported improvement in all domains of diabetes education and management. From baseline, PCPs reported improvement in their confidence to serve as the T1D provider for their community (pre vs post: 43.8% vs 68.8%, p=0.005), manage insulin therapy (pre vs post: 62.8% vs 84.3%, p=0.002), and identify symptoms of diabetes distress (pre vs post: 62.8% vs 84.3%, p=0.002) post-intervention. Compared to pre-intervention, providers reported significant improvement in their confidence in all aspects of diabetes technology including prescribing technology (41.2% vs 68.6%, p=0.001), managing insulin pumps (41.2% vs 68.6%, p=0.001) and hybrid closed loop (10.2% vs 26.5%, p=0.033), and interpreting sensor data (41.2% vs 68.6%, p=0.001) post-intervention.DiscussionPCPs who participated in Project ECHO Diabetes reported increased confidence in diabetes management, with notable improvement in their ability to prescribe, manage, and troubleshoot diabetes technology. These data support the use of tele-education of PCPs to increase confidence in diabetes technology management as a feasible strategy to advance equity in diabetes management and outcomes

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. Variant annotation was supported by software resources provided via the Caché Campus program of the InterSystems GmbH to Alexander Teumer