Deborah Thompson

Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis

Background: Insulinemia and type 2 diabetes (T2D) have been associated with endometrial cancer risk in numerous observational studies. However, the causality of these associations is uncertain. Here we use a Mendelian randomization (MR) approach to assess whether insulinemia and T2D are causally associated with endometrial cancer. Methods: We used single nucleotide polymorphisms (SNPs) associated with T2D (49 variants), fasting glucose (36 variants), fasting insulin (18 variants), early insulin secretion (17 variants), and body mass index (BMI) (32 variants) as instrumental variables in MR analyses. We calculated MR estimates for each risk factor with endometrial cancer using an inverse-variance weighted method with SNP-endometrial cancer associations from 1287 case patients and 8273 control participants. Results: Genetically predicted higher fasting insulin levels were associated with greater risk of endometrial cancer (odds ratio [OR] per standard deviation = 2.34, 95% confidence internal [CI] = 1.06 to 5.14, P = .03). Consistently, genetically predicted higher 30-minute postchallenge insulin levels were also associated with endometrial cancer risk (OR = 1.40, 95% CI = 1.12 to 1.76, P = .003). We observed no associations between genetic risk of type 2 diabetes (OR = 0.91, 95% CI = 0.79 to 1.04, P = .16) or higher fasting glucose (OR = 1.00, 95% CI = 0.67 to 1.50, P = .99) and endometrial cancer. In contrast, endometrial cancer risk was higher in individuals with genetically predicted higher BMI (OR = 3.86, 95% CI = 2.24 to 6.64, P = 1.2x10-6). Conclusion: This study provides evidence to support a causal association of higher insulin levels, independently of BMI, with endometrial cancer risk.

Epidemiology and risk factors for hospital-acquired methicillin-resistant Staphylococcus aureus among burn patients.

Methicillin-resistant Staphylococcus aureus (MRSA) is a substantial source of morbidity among burn patients. The objectives of this study were to determine the feasibility and efficacy of surveillance cultures and isolation precautions on limiting the transmission of MRSA among burn patients and to determine risk factors for the development of hospital-acquired MRSA (HA-MRSA). All patients admitted to the burn service from January 2007 to June 2009 were screened by nasal swab culture on admission and weekly thereafter. Other sites were cultured based on clinical suspicion. Patients with MRSA were immediately placed on isolation precautions. Community-acquired MRSA (CA-MRSA) and HA-MRSA were defined as identification of the organism <72 hours from admission (CA-MRSA) or ≥72 hours after admission (HA-MRSA). Charts were retrospectively analyzed to identify risk factors for development of HA. Screening compliance was 100%. Seventy MRSA cases were identified in 752 admissions (9% incidence), including 30 cases of CA-MRSA and 40 cases of HA-MRSA. Over the 30-month study period, HA-MRSA incidence decreased according to a significant linear trend. Independent risk factors for the development of HA-MRSA on multivariate analysis included length of stay >7 days (odds ratio [OR] 12.0, 95% confidence interval [CI] 1.6–91), TBSA affected >10% (OR 6.1, CI 2.6–14.2), age >30 years (OR 4.9, CI 2.0–12.0), and inhalation injury (OR 3.5, CI 1.0–11.7). Surveillance cultures with isolation precautions are practical and effective for preventing HA-MRSA among burn patients. Older patients with prolonged hospital stays, large wounds, and inhalation injury are at greatest risk.

Discord among Performance Measures for Central Line- Associated Bloodstream Infection

BACKGROUND Central line-associated bloodstream infection (CLABSI) is a national target for mandatory reporting and a Centers for Medicare and Medicaid Services target for value-based purchasing. Differences in chart review versus claims-based metrics used by national agencies and groups raise concerns about the validity of these measures. OBJECTIVE Evaluate consistency and reasons for discordance among chart review and claims-based CLABSI events. METHODS We conducted 2 multicenter retrospective cohort studies within 6 academic institutions. A total of 150 consecutive patients were identified with CLABSI on the basis of National Healthcare Safety Network (NHSN) criteria (NHSN cohort), and an additional 150 consecutive patients were identified with CLABSI on the basis of claims codes (claims cohort). All events had full-text medical record reviews and were identified as concordant or discordant with the other metric. RESULTS In the NHSN cohort, there were 152 CLABSIs among 150 patients, and 73.0% of these cases were discordant with claims data. Common reasons for the lack of associated claims codes included coding omission and lack of physician documentation of bacteremia cause. In the claims cohort, there were 150 CLABSIs among 150 patients, and 65.3% of these cases were discordant with NHSN criteria. Common reasons for the lack of NHSN reporting were identification of non-CLABSI with bacteremia meeting Centers for Disease Control and Prevention (CDC) criteria for an alternative infection source. CONCLUSION Substantial discordance between NHSN and claims-based CLABSI indicators persists. Compared with standardized CDC chart review criteria, claims data often had both coding omissions and misclassification of non-CLABSI infections as CLABSI. Additionally, claims did not identify any additional CLABSIs for CDC reporting. NHSN criteria are a more consistent interhospital standard for CLABSI reporting.

Exome array analysis identifies GPR35 as a novel susceptibility gene for anthracycline-induced cardiotoxicity in childhood cancer.

Objectives Pediatric cancer survivors are a steadily growing population; however, chronic anthracycline-induced cardiotoxicity (AIC) is a serious long-term complication leading to considerable morbidity. We aimed to identify new genes and low-frequency variants influencing the susceptibility to AIC for pediatric cancer patients. Patients and methods We studied the association of variants on the Illumina HumanExome BeadChip array in 83 anthracycline-treated pediatric cancer patients. In addition to single-variant association tests, we carried out a gene-based analysis to investigate the combined effects of common and low-frequency variants to chronic AIC. Results Although no single-variant showed an association with chronic AIC that was statistically significant after correction for multiple testing, we identified a novel significant association for G protein-coupled receptor 35 (GPR35) by gene-based testing, a gene with potential roles in cardiac physiology and pathology (P=7.0×10−6), which remained statistically significant after correction for multiple testing (PFDR=0.03). The greatest contribution to this observed association was made by rs12468485, a missense variant (p.Thr253Met, c.758C>T, minor allele frequency=0.04), with the T allele associated with an increased risk of chronic AIC and more severe symptomatic cardiac manifestations at low anthracycline doses. Conclusion Using exome array data, we identified GPR35 as a novel susceptibility gene associated with chronic AIC in pediatric cancer patients.

Brucella abortus Exposure during an Orthopedic Surgical Procedure in New Mexico, 2010

Brucellosis, a zoonotic disease transmitted through inhalation of infectious aerosolized particles, is endemic in many areas, including Mexico.(1, 2, 3, 4) Manifestations of disease can range from subclinical illness to osteoarticular disease and chronic sequelae.(4) It is a potential occupational hazard among laboratory workers.(3) Although Brucella infection is not usually a risk to medical staff, prosthetic joint infections have been encountered during surgery.(5–9) We report a case of periprosthetic Brucella infection and the subsequent investigation into possible transmission to operating room and laboratory staff. Objectives of the investigation included infection prevention, case-finding and examination into potential routes of Brucella spp. transmission.

Genetic predictors of testosterone and their associations with cardiovascular disease and risk factors: A Mendelian randomization investigation.

Background Testosterone supplementation has been linked to increased cardiovascular disease risk in some observational studies. The causal role of testosterone can be investigated using a Mendelian randomization approach. Methods and results We assessed genetic associations of variants in two gene regions (SHBG and JMJD1C) with several cardiovascular risk factors (lipids, adiponectin, blood pressure, anthropometric traits) plus male pattern baldness, including control outcomes and potential mediators. We assessed genetic associations with coronary artery disease (CAD) risk in the CARDIoGRAMplusC4D consortium (171,191 individuals including 60,801 cases), and associations with CAD and ischaemic stroke risk in the UK Biobank (367,643 individuals including 25,352 CAD cases and 3650 ischaemic stroke cases). Genetic predictors of increased serum testosterone were associated with lipids, blood pressure, and height. There was some evidence of an association with risk of CAD (SHBG gene region: odds ratio (OR) 0.95 per 1 unit increase in log-transformed testosterone [95% confidence interval: 0.81–1.12, p = 0.55]; JMJD1C gene region: OR 1.24 [1.01–1.51, p = 0.04]) and ischaemic stroke both overall (SHBG: OR 1.05 [0.64, 1.73, p = 0.83]; JMJD1C: OR 2.52 [1.33, 4.77, p = 0.005]) and in men. However, associations with some control outcomes were in the opposite direction to that expected. Conclusions Sex hormone-related mechanisms appear to be relevant to cardiovascular risk factors and for stroke (particularly for men). However, the extent that these findings are specifically informative about endogenous testosterone or testosterone supplementation is unclear. These findings underline a fundamental limitation for the use of Mendelian randomization where biological knowledge about the function of genetic variants is uncertain.

Measuring Antibiotic Appropriateness for Urinary Tract Infections in Nursing Home Residents

We assessed the appropriateness of initiating antibiotics in 49 nursing home (NH) residents receiving antibiotics for urinary tract infection (UTI) using 3 published algorithms. Overall, 16 residents (32%) received prophylaxis, and among the 33 receiving treatment, the percentage of appropriate use ranged from 15% to 45%. Opportunities exist for improving UTI antibiotic prescribing in NH. Infect Control Hosp Epidemiol 2017;38:998-1001.