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Isolation of bacterial small colony variants (SCVs) from clinical specimens is not uncommon and can fundamentally change the outcome of the associated infections. Bacterial SCVs often emerge with their normal colony phenotype (NCV) co-isolates in the same sample. The basis of SCV emergence in vivo is not well understood in Gram-negative bacteria. In this study, we interrogated the causal genetic lesions of SCV growth in three pairs of NCV and SCV co-isolates of Escherichia coli, Citrobacter freundii, and Enterobacter hormaechei. We confirmed SCV emergence was attributed to limited genomic mutations: 4 single nucleotide variants in the E. coli SCV, 5 in C. freundii, and 8 in E. hormaechei. In addition, a 10.2 kb chromosomal segment containing 11 genes was deleted in the E. hormaechei SCV isolate. Each SCV had at least one coding change in a gene associated with bacterial oxidative respiration and another involved in iron capture. Chemical and genetic rescue confirmed defects in heme biosynthesis for E. coli and C. freundii and lipoic acid biosynthesis in E. hormaachei were responsible for the SCV phenotype. Prototrophic growth in all 3 SCV Enterobacteriaceae species was unaffected under anaerobic culture conditions in vitro, illustrating how SCVs may persist in vivo.

Detection of Covid-19 through a Citywide Surveillance Platform The Seattle Flu study, initiated in 2018, mailed kits for home collection of midnasal swabs to people reporting respiratory symptoms. ...

Children are strikingly underrepresented in COVID-19 case counts. In the United States, children represent 22% of the population but only 1.7% of confirmed SARS-CoV-2 cases as of April 2, 2020. One possibility is that symptom-based viral testing is less likely to identify infected children, since they often experience milder disease than adults. Here, to better assess the frequency of pediatric SARS-CoV-2 infection, we serologically screen 1,775 residual samples from Seattle Children’s Hospital collected from 1,076 children seeking medical care during March and April of 2020. Only one child was seropositive in March, but seven were seropositive in April for a period seroprevalence of ≈1%. Most seropositive children (6/8) were not suspected of having had COVID-19. The sera of seropositive children have neutralizing activity, including one that neutralized at a dilution > 1:18,000. Therefore, an increasing number of children seeking medical care were infected by SARS-CoV-2 during the early Seattle outbreak despite few positive viral tests., COVID-19 disease is less common in children than adults, but the extent to which SARS-CoV-2 infections are missed through symptom-driven testing is not well understood. In this study, the authors show that approximately 1% of children seeking care for reasons other than COVID-19 at a Seattle hospital in March/April 2020 were seropositive for SARS-CoV-2.

A series of unfortunate events The history of how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread around the planet has been far from clear. Several narratives have been propagated by social media and, in some cases, national policies were forged in response. Now that many thousands of virus sequences are available, two studies analyzed some of the key early events in the spread of SARS-CoV-2. Bedford et al. found that the virus arrived in Washington state in late January or early February. The viral genome from the first case detected had mutations similar to those found in Chinese samples and rapidly spread and dominated subsequent undetected community transmission. The other viruses detected had origins in Europe. Worobey et al. found that early introductions into Germany and the west coast of the United States were extinguished by vigorous public health efforts, but these successes were largely unrecognized. Unfortunately, several major travel events occurred in February, including repatriations from China, with lax public health follow-up. Serial, independent introductions triggered the major outbreaks in the United States and Europe that still hold us in the grip of control measures. Science, this issue p. 571, p. 564, The first case of SARS-CoV-2 in Washington state occurred at the end of January and, by going undetected, sparked community transmission., After its emergence in Wuhan, China, in late November or early December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus rapidly spread globally. Genome sequencing of SARS-CoV-2 allows the reconstruction of its transmission history, although this is contingent on sampling. We analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington state in the United States. We find that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020, which subsequently spread locally before active community surveillance was implemented.

Executive Summary This document updates the 1999 World Health Organization (WHO) classification of diabetes. It prioritizes clinical care and guides health professionals in choosing appropriate treatments at the time of diabetes diagnosis, and provides practical guidance to clinicians in assigning a type of diabetes to individuals at the time of diagnosis. It is a compromise between clinical and aetiological classification because there remain gaps in knowledge of the aetiology and pathophysiology of diabetes. While acknowledging the progress that is being made towards a more precise categorization of diabetes subtypes, the aim of this document is to recommend a classification that is feasible to implement in different settings throughout the world. The revised classification is presented in Table 1. Unlike the previous classification, this classification does not recognize subtypes of type 1 diabetes and type 2 diabetes and includes new types of diabetes ("hybrid types of diabetes" and "unclassified diabetes").

Background: Event accumulation patterns in event-driven trials inform forecasting of trial size and duration. It is hypothesized that trials enrol a healthier cohort who have lower early cardiovascular (CV) event rates that increase during follow-up as surviving patients age and accumulate comorbidities. We present hazard rate patterns for incident CV events in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Methods: Using adjudicated endpoints from the intention-to-treat population, Weibull models show whether hazards for these CV events were increasing (shape parameter>1), decreasing ( Results: The Figure shows hazard rate over time. Weibull shape point estimates (95% CI) were MACE-4 0.96 (0.92, 1.01); ACM 1.14 (1.08, 1.21); CV death 1.(1.01, 1.16); F/NFMI 0.96 (0.89, 1.03); F/NFSt 0.93 (0.85, 1.03); UA 0.90 (0.79, 1.01); HF 0.98 (0.90, 1.08). Annual event rates (per 100 pt-years) were CV death: 1.5, 1.6, 2.0, 1.9, 2.7; ACM: 2.1, 2.3, 2.8, 3.0, 3.8. Conclusions: Hazard rates were constant for all events except CV death and ACM, which had small significant increased risk over time. Our findings may inform the planning and conduct of future trials in diabetes. Disclosure M. Bethel: Research Support; Self; AstraZeneca, Merck Sharp & Dohme Corp., Merck Serono. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; AstraZeneca. Other Relationship; Self; Sanofi. Consultant; Self; Theracos, Inc.. Research Support; Self; GlaxoSmithKline plc. H. Sourij: Speaker's Bureau; Self; Boehringer Ingelheim GmbH, Novo Nordisk A/S, Amgen Inc., Sanofi, MSD K.K.. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH, MSD K.K., GI Dynamics Inc.. S.R. Stevens: None. Y. Lokhnygina: None. R.D. Lopes: Consultant; Self; Bayer AG, Boehringer Ingelheim GmbH. Other Relationship; Self; Bristol-Myers Squibb Company. Consultant; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; GlaxoSmithKline plc., Medtronic. Consultant; Self; Merck & Co., Inc.. Other Relationship; Self; Pfizer Inc.. A. Adler: None. D.K. McGuire: Consultant; Self; AstraZeneca, Sanofi-Aventis, Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Pfizer Inc., Novo Nordisk A/S. Research Support; Self; AstraZeneca, Sanofi-Aventis, Janssen Pharmaceuticals, Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Lexicon Pharmaceuticals, Inc., Eisai Inc., GlaxoSmithKline plc., Esperion Therapeutics. E. Peterson: Research Support; Self; Merck & Co., Inc.. Consultant; Self; Merck & Co., Inc.. Research Support; Self; AstraZeneca. Consultant; Self; AstraZeneca. R.R. Holman: Research Support; Self; AstraZeneca, Merck & Co., Inc., Bayer AG. Advisory Panel; Self; Elcelyx Therapeutics, Inc., Novartis AG, Novo Nordisk A/S. Other Relationship; Self; Bayer AG. Advisory Panel; Self; Merck & Co., Inc.. Other Relationship; Self; AstraZeneca.

Clinical isolates of Pseudomonas aeruginosa from patients with cystic fibrosis (CF) are known to differ from those associated with non-CF hosts by colony morphology, drug susceptibility patterns, and genomic hypermutability. Pseudomonas aeruginosa isolates from CF patients have long been recognized for their overall reduced rate of antimicrobial susceptibility, but their intraclonal MIC heterogeneity has long been overlooked. Using two distinct cohorts of clinical strains ( n = 224 from 56 CF patients, n = 130 from 68 non-CF patients) isolated in 2013, we demonstrated profound Etest MIC heterogeneity in CF P. aeruginosa isolates in comparison to non-CF P. aeruginosa isolates. On the basis of whole-genome sequencing of 19 CF P. aeruginosa isolates from 9 patients with heterogeneous MICs, the core genome phylogenetic tree confirmed the within-patient CF P. aeruginosa clonal lineage along with considerable coding sequence variability. No extrachromosomal DNA elements or previously characterized antibiotic resistance mutations could account for the wide divergence in antimicrobial MICs between P. aeruginosa coisolates, though many heterogeneous mutations in efflux and porin genes and their regulators were present. A unique OprD sequence was conserved among the majority of isolates of CF P. aeruginosa analyzed, suggesting a pseudomonal response to selective pressure that is common to the isolates. Genomic sequence data also suggested that CF pseudomonal hypermutability was not entirely due to mutations in mutL , mutS , and uvr . We conclude that the net effect of hundreds of adaptive mutations, both shared between clonally related isolate pairs and unshared, accounts for their highly heterogeneous MIC variances. We hypothesize that this heterogeneity is indicative of the pseudomonal syntrophic-like lifestyle under conditions of being “locked” inside a host focal airway environment for prolonged periods. IMPORTANCE Patients with cystic fibrosis endure “chronic focal infections” with a variety of microorganisms. One microorganism, Pseudomonas aeruginosa , adapts to the host and develops resistance to a wide range of antimicrobials. Interestingly, as the infection progresses, multiple isogenic strains of P. aeruginosa emerge and coexist within the airways of these patients. Despite a common parental origin, the multiple strains of P. aeruginosa develop vastly different susceptibility patterns to actively used antimicrobial agents—a phenomenon we define as “heterogeneous MICs.” By sequencing pairs of P. aeruginosa isolates displaying heterogeneous MICs, we observed widespread isogenic gene lesions in drug transporters, DNA mismatch repair machinery, and many other structural or cellular functions. Coupled with the heterogeneous MICs, these genetic lesions demonstrated a symbiotic response to host selection and suggested evolution of a multicellular syntrophic bacterial lifestyle. Current laboratory standard interpretive criteria do not address the emergence of heterogeneous growth and susceptibilities in vitro with treatment implications.

Fecal microbiota transplantation (FMT) is a safe and effective therapy for adults with recurrent Clostridium difficile colitis, but data regarding FMT in children are limited and focus on colonoscopic administration of FMT. We present 10 consecutive children who received FMT via nasogastric tube for treatment of recurrent C difficile infection. Median age was 5.4 years, and 30% were receiving simultaneous immunosuppression. Median follow-up was 44 days, and 90% of patients resolved their C difficile infection; one patient relapsed 2 months later after receiving antibiotics. FMT via nasogastric tube appears safe, well tolerated, and effective in treating pediatric recurrent C difficile colitis.

Clinical isolates ofPseudomonas aeruginosa (Pa)from patients with cystic fibrosis (CF) are known to differ from those associated with infections of non-CF hosts in colony morphology, drug susceptibility patterns, and genomic hypermutability. AlthoughPaisolates from CF have long been recognized for their overall higher resistance rate calculated generally by reduced “percent susceptible”, this study takes the approach to compare and contrast Etest MIC distributions between two distinct cohorts of clinical strains (n=224 from 56 CF patients and n=130 from 68 non-CF patients respectively) isolated in 2013. Logarithmic transformed MIC (logMIC) values of 11 antimicrobial agents were compared between the two groups. CF isolates tended to produce heterogeneous and widely dispersed MICs compared to non-CF isolates. By applying a test for equality of variances, we were able to confirm that the MICs generated from CF isolates against 9 out of the 11 agents were significantly more dispersed than those from non-CF (pPaisolates, divergent gain- or loss-of-function mutations in efflux and porin genes and their regulators between isogenic or intra-clonal associates were evident. Not one, not a few, but the net effect all adaptive mutational changes in the genomes of CFPa, both shared and unshared between isogenic strains, are responsible for the divergent heteroresistance patterns. Moreover, the isogenic variations are suggestive of a bacterial syntrophic lifestyle when “lockedȍ inside a host focal airway environment over prolonged periods.Significance statementBacterial heteroresistance is associated with niche specialized organisms interacting with host species for prolonged period of time, medically characterized by “chronic focal infections”. A prime example is found inPseudomonas aeruginosaisogenic/non-homogeneous isolates from patient airways with cystic fibrosis. The development of pseudomonal polarizing MICsin vitroto many actively used antimicrobial agents among isogenic isolates and “Eagle-type” heteroresistance patterns are common and characteristic. Widespread isogenic gene lesions were evident for defects in drug transporters, DNA mismatch repair, and many other structural or cellular functions—a result of pseudomonal symbiotic response to host selection. Co-isolation of extremely susceptible and resistant isogenicPastrains suggests intra-airway evolution of a multicellular syntrophic bacterial lifestyle, which has laboratory interpretation and clinical treatment implications.

The objective of this study is to describe the epidemiology of intestinal carriage with extended-spectrum-cephalosporin-resistant Enterobacteriaceae in children with index infections with these organisms. Patients with resistant Escherichia coli or Klebsiella bacteria isolated from the urine or a normally sterile site between January 2006 and December 2010 were included in this study. Available infection and stool isolates underwent phenotypic and molecular characterization. Clinical data relevant to the infections were collected and analyzed. Overall, 105 patients were identified with 106 extended-spectrum-cephalosporin-resistant E. coli ( n = 92) or Klebsiella ( n = 14) strains isolated from urine or a sterile site. Among the 27 patients who also had stool screening for resistant Enterobacteriaceae , 17 (63%) had intestinal carriage lasting a median of 199 days (range, 62 to 1,576). There were no significant differences in demographic, clinical, and microbiological variables between those with and those without intestinal carriage. Eighteen (17%) patients had 37 subsequent resistant Enterobacteriaceae infections identified: 31 urine and 6 blood. In a multivariable analysis, antibiotic intake in the 91 days prior to subsequent urine culture was significantly associated with subsequent urinary tract infection with a resistant organism (hazard ratio, 14.3; 95% confidence interval [CI], 1.6 to 130.6). Intestinal carriage and reinfection were most commonly due to bacterial strains of the same sequence type and with the same resistance determinants as the index extended-spectrum-cephalosporin-resistant Enterobacteriaceae , but carriage and reinfection with different resistant Enterobacteriaceae strains also occurred.

Background Influenza epidemics and pandemics cause significant morbidity and mortality. An effective response to a potential pandemic requires the infrastructure to rapidly detect and contain new and emerging flu strains at a population level. The objective of this study was to use data gathered simultaneously from community and hospital sites to develop a model of how flu enters and spreads in a population. Methods In the 2018–2019 season, we enrolled individuals with respiratory illness from community sites throughout the Seattle area, including homeless shelters, childcare facilities, Seattle-Tacoma International Airport, workplaces, college campuses, clinics, and at home (Figure 1). We collected data and nasal swabs from individuals with at least two respiratory symptoms. Additionally, we collected residual nasal swabs and data from individuals who sought care at four regional hospitals. Home-based self-testing for influenza and prediction models for influenza were piloted. Swabs were tested with a multiplex molecular assay, and influenza whole-genome sequencing was performed. Geospatial mapping and computational modeling platforms were developed to characterize regional spread of respiratory pathogens. Results A total of 18,847 samples were collected in the 2018–2019 season. Of those tested to date, 291/3,653 (8%) community and 2,393/11,273 (21%) hospital samples have influenza detected. Of the community enrollments, 39% had influenza-like illness. Community enrollees were in age groups not well-represented from hospitals. Influenza A/H3N2 activity peaked on college campuses and homeless shelters 2 weeks before the peak in hospitals. We observed multiple independent introductions of influenza strains into the city and evidence of sustained transmission chains within the city (Figures 2 and 3). Conclusion Utilizing the city-wide infrastructure we developed, we observed the introduction of influenza A/H3N2 into the community before the hospital and evidence of transmissions of unique strains into and within the Seattle area. These data provide the blueprint for implementing city-wide, community-based surveillance systems for rapid detection, real-time assessment of transmission patterns, and interruption of spread of seasonal or pandemic strains. Disclosures Helen Y. Chu, MD MPH, Merck (Advisor or Review Panel member), Michael Boeckh, MD PhD, Ablynx (Consultant, Grant/Research Support), Ansun Biopharma (Consultant, Grant/Research Support), Bavarian Nordic (Consultant), Gilead (Consultant, Grant/Research Support), GlaxoSmithKline (Consultant), Vir Bio (Consultant, Grant/Research Support), Janet A. Englund, MD, Chimerix (Grant/Research Support), GlaxoSmithKline (Grant/Research Support), MedImmune/Astrazeneca (Grant/Research Support), Meissa Vaccines (Consultant), Merck (Grant/Research Support),Novavax (Grant/Research Support), Sanofi Pastuer (Consultant), Matthew Thompson, MD, Alere Inc. (Research Grant or Support), Roche Molecular Diagnostics (Consultant, Research Grant or Support, Speaker’s Bureau), . Other Authors: No reported disclosures.

Metformin is a safe, well-tolerated, inexpensive treatment that can be given in addition to current standard-of-care therapies for prostate cancer. Its use might mitigate the deleterious side effects of castration and exert an additional anticancer effect. It will be incorporated in the STAMPEDE trial platform in summer 2016. This will test its true utility as a repurposed treatment for men with high-risk locally advanced or metastatic prostate cancer at first presentation.

Epidemiologists have found relationships between diabetes and cardiovascular disease and between the degree of hyperglycemia and cardiovascular disease. Clinical trials, however, have been less successful in providing convincing evidence to support changes in clinical care. Observational data from the DCCT and interventional data—notably, results related to metformin use from the UKPDS—support glucose lowering. Several ongoing studies in individuals with diabetes and “pre-diabetes” and in those with and without existing cardiovascular disease seek a definitive answer. If positive, these studies will justify even greater efforts toward glycemic control, and they may support blood glucose lowering in individuals without diabetes.

Multidrug-resistant (MDR) Enterobacteriaceae infections are associated with increased morbidity. We describe a 20-year-old hematopoietic cell transplantation recipient with recurrent MDR Klebsiella pneumoniae infection, prolonged intestinal colonization, and subsequent intestinal decontamination. Further study should evaluate stool surveillance, molecular typing, and fecal microbiota transplantation for patients with intestinal MDR Enterobacteriaceae carriage.

OBJECTIVE To identify risk factors for diabetic lower-extremity peripheral sensory neuropathy prospectively in a cohort of U.S. veterans with diabetes. RESEARCH DESIGN AND METHODS General medicine clinic outpatients with diabetes were followed prospectively for the development of insensitivity to the 5.07 monofilament on the foot. RESULTS Of 775 subjects, 388 (50%) had neuropathy at baseline. Of the 387 subjects without neuropathy at baseline, 288 were followed up, and of these, 58 (20%) developed neuropathy. Multivariate logistic regression modeling of prevalent neuropathy controlling for sex and race revealed independent and significant associations with age, duration of diabetes, glycohemoglobin level, height, history of lower-extremity ulceration, callus, and edema; an independent and inverse correlation was noted with ankle-arm index. Risk factors for incident neuropathy in multivariate logistic regression included age, baseline glycohemoglobin level, height, history of ulcer, and CAGE screening instrument alcohol score; current smoking and albumin level were inversely associated with risk. CONCLUSIONS Poorer glycemic control increases the risk of neuropathy and is amenable to intervention. Height and age directly increase risk of neuropathy and may help identify patients at risk. A proportion of neuropathy in diabetic veterans is probably due to or worsened by alcohol ingestion. Neuropathy was less common in current smokers than subjects not currently smoking.

What you need to know New evidence and developments regarding the management of blood glucose levels, antiplatelet therapy, and erectile dysfunction prompted this update of the 2009 guidance. There were safety concerns surrounding some blood glucose lowering medicines, new evidence on new dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, new indications and combinations for licensed drugs, and the potential impact of drugs coming off patent on health and economic issues. New evidence and safety issues relating to the off label use of antiplatelet therapy (aspirin and clopidogrel) in the primary prevention of cardiovascular disease were also considered. Type 2 diabetes affects 6% of the UK population1 and is commonly associated with obesity, physical inactivity, raised blood pressure, and disturbed blood lipid levels. It causes long term microvascular and macrovascular complications, plus reduced quality of life and life expectancy. The management of diabetes is complex and needs to address the prevention of cardiovascular disease and microvascular disease and the detection and management of early vascular complications. This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE),2 recently updated due to the availability of new evidence and developments. The article also summarises a selection of recommendations which still stand. #### What’s new in this guidance

Resistance to extended-spectrum β-lactams is increasing worldwide among Escherichia coli and has been linked to a small number of emergent clones (e.g. ST38, ST131 and ST405) recovered from extraintestinal infections in community and hospital settings. There are, however, limited data about the relative contributions of bacterial strains, plasmids and β-lactamase genes to extended-spectrum β-lactam resistance in paediatric infections. We performed an extensive molecular analysis of phylogenetic, virulence and antibiotic resistance-related properties of 49 previously reported serial E. coli isolates recovered during 1999–2007 at Seattle Children's Hospital (Seattle, WA). Class C enzyme CMY-2 and class A enzyme CTX-M-15 were the most prominent extended-spectrum β-lactam resistance enzymes in the collection, first appearing in this patient population in 2001 and 2003, respectively, and then steadily increasing in frequency over the remainder of the study period. Among 19 CMY-2-positive isolates, 16 distinct STs were detected ( D =98.25%, 95% CI 96–100.25%), indicating that CMY spread is non-clonal at the host strain level. In contrast, among ten CTX-M-15-positive isolates, three STs were detected ( D =37.78%, 95% CI 2.36–73.20%), of which eight represented the worldwide-disseminated ST131 lineage, consistent with clonal spread of CTX-M-15-associated resistance. fimH TR subtyping of ten ST131 isolates (including two CTX-M-negative isolates) revealed that, within ST131, carriage of allele fimH TR 30 correlated with CTX-M-15 positivity, whilst carriage of non- fimH TR 30 alleles correlated with carriage of non-CTX-M enzymes. Thus, spread of CMY-2 is non-clonal at the ST level, but clonal spread of CTX-M-15 may be associated with a specific fimH TR -defined sublineage of ST131.

randomized controlled trials to help determine if intensive blood glucose control has benefit in reducing the risk of congestive heart failure (CHF). The study revealed that there was no significant reduction in risk of CHF among individuals randomized to intensive versus standard blood glucose control groups. The authors rightly point out the presence of important heterogeneity among the trials with regard to the use of thiazolidinediones (TZDs). As expected, among the 4 trials that had a high rate of TZD use (ie, PROactive, ACCORD, VADT, and RECORD), the risk of CHF was elevated in individuals randomized to intensive blood glucose control. On the other hand, among the remaining 3 trials (ie, UKPDS, ADVANCE, and VA-CSDM), the risk ratio was close to null with a wide CI, highlighting the limitedness of the available data (risk ratio 0.96, 95% CI 0.81-1.13). We believe that combining these 2 groups of trials that are fundamentally different with respect to CHF outcomes can give the reader a false sense of adequate power because, in actuality, the 4 trials that used TZDs (agents known to cause heart failure) to lower blood glucose levels are confounded by the intervention itself and, hence, are not appropriate to answer the question whether intensive blood glucose control can reduce the risk of CHF. Therefore, although Castagno et al discussed the various aspects of the observed null finding, it would have been useful to point out that the most relevant data on the topic come from only 2 trials (ie, UKPDS and ADVANCE, not counting the pilot trial with a total of 9 events of interest) and are not sufficiently powered to

OBJECTIVE To examine the association of seal oil and salmon consumption with impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) among Alaska Natives. RESEARCH DESIGN AND METHODS Screening was performed on 666 Yup'ik Eskimos and Athabaskan Indians ≥40 years old in 15 villages. Self-administered questionnaires were used to obtain partial food frequency data. A case was defined as IGT or NIDDM, either newly discovered or known. Newly discovered cases (11 patients with NIDDM and 17 with IGT) were determined by random blood glucose testing followed by a 2-h 75-g oral glucose tolerance test (OGTT) for those with values ≥ 6.72 mmol/l or for subjects with unconfirmed histories of glucose intolerance. Known cases included 26 patients with NIDDM and 1 with IGT. Control subjects had random blood glucoses RESULTS Compared with less-than-daily consumption, both daily seal oil (odds ratio [OR] 0.2, 95% confidence interval [CI] 0.1–0.8) and daily salmon consumption (OR 0.5, CI 0.2–1.1) were associated with a lower prevalence of glucose intolerance, controlling for age, ethnicity, body mass index, and sex. The effects were similar when limited to newly discovered cases: OR 0.3, CI 0.1–1.3 for seal oil and OR 0.4, CI 0.1–1.3 for salmon. Consumption of seal oil at least five times per week was required to reduce risk. CONCLUSIONS Consumption of seal oil and salmon, high in ω-3 fatty acids, appears to lower the risk of glucose intolerance and is a potentially modifiable risk factor for NIDDM in Alaska Natives.

BACKGROUND Surgical site infections (SSIs) cause significant morbidity and mortality in patients undergoing cardiovascular (CV) surgery. Following an increase in SSIs in this population, driven by a high rate in those with delayed closure, we implemented an intervention to reduce these infections and assessed the intervention using both population- and patient-level analyses. METHODS An intervention drawing from existing guidelines and targeting preoperative preparation of the patient, prophylactic antibiotics, and postoperative incision care was implemented. Special attention was paid to standardizing the care of the incision of patients with delayed closure. National Healthcare Safety Network criteria were used to prospectively identify SSIs. Population-level intervention effect was assessed using interrupted time series. To assess intervention adherence and effect in our patient population, retrospective chart review was performed on a cohort of patients undergoing cardiac procedures pre- and postintervention. Multivariate analysis was used to assess risk of SSI at the patient level. RESULTS Timely preoperative prophylactic antibiotic dosing increased from 60% preintervention to 92% postintervention, and redosing during prolonged surgeries increased from 5% to 79% (both, P

Vijaya L Soma1, Xuan Qin2, Chuan Zhou1, Amanda Adler1, Jessica E Berry2, Danielle M Zerr11Department of Pediatrics, 2Department of Laboratory Medicine, University of Washington, Seattle, WA, USAAbstract: Chlorhexidine gluconate (CHG) is a topical antiseptic used in a myriad of clinical settings. Recently, CHG baths have been shown to decrease multidrug-resistant organism acquisition and infections and catheter-associated bloodstream infections. The present study examined the effects of daily bathing with CHG on the recovery and antimicrobial susceptibility of cultivable cutaneous bacteria. The objectives of this study were to (1) explore the effects of clinical CHG bathing on cultivable cutaneous bacteria, (2) study the relationship between CHG minimum inhibitory concentration and antimicrobial susceptibility of coagulase-negative staphylococci, and (3) demonstrate the feasibility of the approach so a more definitive study may be performed. Significant decreases in bacterial colony counts and phenotypic diversity occurred with greater CHG exposure. The findings also suggest an inverse relationship between CHG minimum inhibitory concentration and antimicrobial susceptibility. Larger prospective studies are necessary to fully investigate the clinical impact of CHG usage.Keywords: antiseptic, resistance, Staphylococcus, coagulase-negative

Issue: Hand Hygiene (HH) is known to be the most effective way to prevent hospital associated infections. Since 2004, targeted education, hospital wide initiatives and other focused efforts have raised hand hygiene compliance rates in HCWs in our 250 bed inpatient pediatric tertiary care center to a sustained rate above 90%. However, family and visitor compliance rates have lagged. Review of hospital associated infections in our institution indicates that families and visitors can be an important source of infection transmission. Although families and visitors have been actively included in our past efforts to educate about the importance of HH, they have not been specifically targeted.

Objective. —To investigate an outbreak of gram-negative folliculitis in relation to a common exposure, mud wrestling, and identify risk factors for dermatitis among those who mud wrestled. Design. —Case-control study. Setting. —University of Washington, Seattle. Participants. —Two college-residence groups of students. Results. —Cultures from affected students and from mud similar to that used for wrestling yielded Enterobacteriaceae. The odds ratio associated with mud wrestling was 79.5 (95% confidence interval, 13.9 to 895.4). Increased time spent wrestling was associated with increased risk. Skin trauma during wrestling or immersion in the mud increased the risk of infection (odds ratio, 23.1; 95% confidence interval, 1.7 to 1440.4). Conclusions. —Mud wrestling is one cause of pustular follicular dermatitis. Trauma to the skin may be a necessary cofactor for the development of infection. ( JAMA . 1993;269:502-504)

We determined whether the exercise electrocardiogram predicted acute cardiac events during moderate or strenuous physical activity among 3617 asymptomatic, hypercholesterolemic men (age range, 35 to 59 years) who were followed up in the Coronary Primary Prevention Trial. Submaximal exercise test results were obtained at entry and at annual follow-up visits in years 2 through 7. ST-segment depression or elevation (≥ 1 mm or 10 μV-sec) was considered to be a positive test result. The circumstances that surrounded each nonfatal myocardial infarction and coronary heart disease death were determined through a record review. The cumulative incidence of activity-related acute cardiac events was 2% during a mean follow-up period of 7.4 years. The risk was increased 2.6-fold in the presence of clinically silent, exercise-induced, ST-segment changes at entry (95% confidence interval [CI], 1.3 to 5.2) after adjustment for 11 other potential risk factors. Of 62 men who experienced an activity-related event, 11 had a positive test result at entry (sensitivity, 18%; 95% CI, 8 to 27). The specificity of the entry exercise test was 92% (95% CI, 91 to 93). The sensitivity and specificity were similar when the length of follow-up was restricted to 1 year after testing. For a newly positive test result on a follow-up visit, the sensitivity was 24% (95% CI, 12 to 36), and the specificity was 85% (95% CI, 84 to 86); for any positive test result during the study (mean number of tests per subject, 6.2), the sensitivity was 37% (95% CI, 25 to 49), and the specificity was 79% (95% CI, 77 to 80). Our findings suggested that the presence of clinically silent, exercise-induced, ischemic ST-segment changes on a submaximal test was associated with an increased risk of activity-related acute cardiac events. However, this test was not sensitive when used to predict the occurrence of activity-related events among asymptomatic, hypercholesterolemic men. For this reason, the utility of the submaximal exercise test to assess the safety of physical activity among asymptomatic men at risk of coronary heart disease is likely to be limited. ( Arch Intern Med . 1991;151:325-330)