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21.
Ole?A. Andreassen Srdjan Djurovic Wesley?K. Thompson Andrew?J. Schork Kenneth?S. Kendler Michael?C. O’Donovan Dan Rujescu Thomas Werge Martijn van?de?Bunt Andrew?P. Morris Mark?I. McCarthy International Consortium for Blood Pressure GWAS Diabetes Genetics Replication Meta-analysis Consortium Psychiatric Genomics Consortium Schizophrenia Working Group J.?Cooper Roddey Linda?K. McEvoy Rahul?S. Desikan Anders?M. Dale 《American journal of human genetics》2013,92(2):197-209
Several lines of evidence suggest that genome-wide association studies (GWASs) have the potential to explain more of the “missing heritability” of common complex phenotypes. However, reliable methods for identifying a larger proportion of SNPs are currently lacking. Here, we present a genetic-pleiotropy-informed method for improving gene discovery with the use of GWAS summary-statistics data. We applied this methodology to identify additional loci associated with schizophrenia (SCZ), a highly heritable disorder with significant missing heritability. Epidemiological and clinical studies suggest comorbidity between SCZ and cardiovascular-disease (CVD) risk factors, including systolic blood pressure, triglycerides, low- and high-density lipoprotein, body mass index, waist-to-hip ratio, and type 2 diabetes. Using stratified quantile-quantile plots, we show enrichment of SNPs associated with SCZ as a function of the association with several CVD risk factors and a corresponding reduction in false discovery rate (FDR). We validate this “pleiotropic enrichment” by demonstrating increased replication rate across independent SCZ substudies. Applying the stratified FDR method, we identified 25 loci associated with SCZ at a conditional FDR level of 0.01. Of these, ten loci are associated with both SCZ and CVD risk factors, mainly triglycerides and low- and high-density lipoproteins but also waist-to-hip ratio, systolic blood pressure, and body mass index. Together, these findings suggest the feasibility of using genetic-pleiotropy-informed methods for improving gene discovery in SCZ and identifying potential mechanistic relationships with various CVD risk factors. 相似文献
22.
Carlos Alberto Pires Pereira Alexandre R. Marra Luis Fernando Aranha Camargo Ant?nio Carlos Campos Pignatari Teresa Sukiennik Paulo Renato Petersen Behar Eduardo Alexandrino Servolo Medeiros Julival Ribeiro Evelyne Gir?o Luci Correa Carla Guerra Irna Carneiro Carlos Brites Marise Reis Marta Antunes de Souza Regina Tranchesi Cristina U. Barata Michael B. Edmond Brazilian SCOPE Study Group 《PloS one》2013,8(7)
Background
Nosocomial bloodstream infections (nBSIs) are an important cause of morbidity and mortality and are the most frequent type of nosocomial infection in pediatric patients.Methods
We identified the predominant pathogens and antimicrobial susceptibilities of nosocomial bloodstream isolates in pediatric patients (≤16 years of age) in the Brazilian Prospective Surveillance for nBSIs at 16 hospitals from 12 June 2007 to 31 March 2010 (Br SCOPE project).Results
In our study a total of 2,563 cases of nBSI were reported by hospitals participating in the Br SCOPE project. Among these, 342 clinically significant episodes of BSI were identified in pediatric patients (≤16 years of age). Ninety-six percent of BSIs were monomicrobial. Gram-negative organisms caused 49.0% of these BSIs, Gram-positive organisms caused 42.6%, and fungi caused 8.4%. The most common pathogens were Coagulase-negative staphylococci (CoNS) (21.3%), Klebsiella spp. (15.7%), Staphylococcus aureus (10.6%), and Acinetobacter spp. (9.2%). The crude mortality was 21.6% (74 of 342). Forty-five percent of nBSIs occurred in a pediatric or neonatal intensive-care unit (ICU). The most frequent underlying conditions were malignancy, in 95 patients (27.8%). Among the potential factors predisposing patients to BSI, central venous catheters were the most frequent (66.4%). Methicillin resistance was detected in 37 S. aureus isolates (27.1%). Of the Klebsiella spp. isolates, 43.2% were resistant to ceftriaxone. Of the Acinetobacter spp. and Pseudomonas aeruginosa isolates, 42.9% and 21.4%, respectively, were resistant to imipenem.Conclusions
In our multicenter study, we found a high mortality and a large proportion of gram-negative bacilli with elevated levels of resistance in pediatric patients. 相似文献23.
Umberto Raucci Rossella Rossi Roberto Da Cas Concita Rafaniello Nadia Mores Giulia Bersani Antonino Reale Nicola Pirozzi Francesca Menniti-Ippolito Giuseppe Traversa Italian Multicenter Study Group for Vaccine Safety in Drug Children 《PloS one》2013,8(7)
Objective
Stevens-Johnson Syndrome (SJS) is one of the most severe muco-cutaneous diseases and its occurrence is often attributed to drug use. The aim of the present study is to quantify the risk of SJS in association with drug and vaccine use in children.Methods
A multicenter surveillance of children hospitalized through the emergency departments for acute conditions of interest is currently ongoing in Italy. Cases with a diagnosis of SJS were retrieved from all admissions. Parents were interviewed on child’s use of drugs and vaccines preceding the onset of symptoms that led to the hospitalization. We compared the use of drugs and vaccines in cases with the corresponding use in a control group of children hospitalized for acute neurological conditions.Results
Twenty-nine children with a diagnosis of SJS and 1,362 with neurological disorders were hospitalized between 1st November 1999 and 31st October 2012. Cases were more frequently exposed to drugs (79% vs 58% in the control group; adjusted OR 2.4; 95% CI 1.0–6.1). Anticonvulsants presented the highest adjusted OR: 26.8 (95% CI 8.4–86.0). Significantly elevated risks were also estimated for antibiotics use (adjusted OR 3.3; 95% CI 1.5–7.2), corticosteroids (adjusted OR 4.2; 95% CI 1.8–9.9) and paracetamol (adjusted OR 3.2; 95% CI 1.5–6.9). No increased risk was estimated for vaccines (adjusted OR: 0.9; 95% CI 0.3–2.8).Discussion
Our study provides additional evidence on the etiologic role of drugs and vaccines in the occurrence of SJS in children. 相似文献24.
25.
Louis Aronne Domenica Rubino Christopher Still Holly Wyatt Colleen Burns Dennis Kim Eduardo Dunayevich for the COR‐II Study Group 《Obesity (Silver Spring, Md.)》2013,21(5):935-943
Objective:
To examine the effects of naltrexone/bupropion (NB) combination therapy on weight and weight‐related risk factors in overweight and obese participants.Design and Methods:
CONTRAVE Obesity Research‐II (COR‐II) was a double‐blind, placebo‐controlled study of 1,496 obese (BMI 30‐45 kg/m2) or overweight (27‐45 kg/m2 with dyslipidemia and/or hypertension) participants randomized 2:1 to combined naltrexone sustained‐release (SR) (32 mg/day) plus bupropion SR (360 mg/day) (NB32) or placebo for up to 56 weeks. The co‐primary endpoints were percent weight change and proportion achieving ≥5% weight loss at week 28.Results:
Significantly (P < 0.001) greater weight loss was observed with NB32 versus placebo at week 28 (?6.5% vs. ?1.9%) and week 56 (?6.4% vs. ?1.2%). More NB32‐treated participants (P < 0.001) experienced ≥5% weight loss versus placebo at week 28 (55.6% vs. 17.5%) and week 56 (50.5% vs. 17.1%). NB32 produced greater improvements in various cardiometabolic risk markers, participant‐reported weight‐related quality of life, and control of eating. The most common adverse event with NB was nausea, which was generally mild to moderate and transient. NB was not associated with increased events of depression or suicidality versus placebo.Conclusion:
NB represents a novel pharmacological approach to the treatment of obesity, and may become a valuable new therapeutic option.26.
Jacques Amar Céline Lange Ga?lle Payros Celine Garret Chantal Chabo Olivier Lantieri Michael Courtney Michel Marre Marie Aline Charles Beverley Balkau Rémy Burcelin D.E.S.I.R. Study Group 《PloS one》2013,8(1)
Aim
We recently described a human blood microbiome and a connection between this microbiome and the onset of diabetes. The aim of the current study was to assess the association between blood microbiota and incident cardiovascular disease.Methods and Results
D.E.S.I.R. is a longitudinal study with the primary aim of describing the natural history of the metabolic syndrome and its complications. Participants were evaluated at inclusion and at 3-, 6-, and 9-yearly follow-up visits. The 16S ribosomal DNA bacterial gene sequence, that is common to the vast majority of bacteria (Eubac) and a sequence that mostly represents Proteobacteria (Pbac), were measured in blood collected at baseline from 3936 participants. 73 incident cases of acute cardiovascular events, including 30 myocardial infarctions were recorded. Eubac was positively correlated with Pbac (r = 0.59; P<0.0001). In those destined to have cardiovascular complications, Eubac was lower (0.14±0.26 vs 0.12±0.29 ng/µl; P = 0.02) whereas a non significant increase in Pbac was observed. In multivariate Cox analysis, Eubac was inversely correlated with the onset of cardiovascular complications, (hazards ratio 0.50 95% CI 0.35–0.70) whereas Pbac (1.56, 95%CI 1.12–2.15) was directly correlated.Conclusion
Pbac and Eubac were shown to be independent markers of the risk of cardiovascular disease. This finding is evidence for the new concept of the role played by blood microbiota dysbiosis on atherothrombotic disease. This concept may help to elucidate the relation between bacteria and cardiovascular disease. 相似文献27.
NIH working group report—using genomic information to guide weight management: From universal to precision treatment 下载免费PDF全文
28.
The relationship of social support with treatment adherence and weight loss in Latinos with type 2 diabetes 下载免费PDF全文
29.
Correction: Guidelines for Accurate and Transparent Health Estimates Reporting: the GATHER statement
Gretchen A. Stevens Leontine Alkema Robert E. Black J. Ties Boerma Gary S. Collins Majid Ezzati John T. Grove Daniel R. Hogan Margaret C. Hogan Richard Horton Joy E. Lawn Ana Maru?i? Colin D. Mathers Christopher J. L. Murray Igor Rudan Joshua A. Salomon Paul J. Simpson Theo Vos Vivian Welch The GATHER Working Group 《PLoS medicine》2016,13(8)
30.
Antonia Barcelo Josep Miquel Bau?a Aina Ya?ez Laura Fueyo Cristina Gomez Monica de la Pe?a Javier Pierola Alberto Rodriguez Manuel Sanchez-de-la-Torre Jorge Abad Olga Mediano Jose Amilibia Maria Jose Masdeu Joaquin Teran Josep Maria Montserrat Mercè Mayos Alicia Sanchez-de-la-Torre Ferran Barbé Spanish Sleep Group 《PloS one》2016,11(3)