Polymorphisms in Nucleotide Excision Repair Genes, Arsenic Exposure, and Non-Melanoma Skin Cancer in New Hampshire

Background: Arsenic exposure may alter the efficiency of DNA repair. UV damage is specifically repaired by nucleotide excision repair (NER), and common genetic variants in NER may increase risk for non-melanoma skin cancer (NMSC). Objective: We tested whether polymorphisms in the NER genes XPA (A23G) and XPD (Asp312Asn and Lys751Gln) modify the association between arsenic and NMSC. Methods: Incident cases of basal and squamous cell carcinoma (BCC and SCC, respectively) were identified through a network of dermatologists and pathology laboratories across New Hampshire. Population-based controls were frequency matched to cases on age and sex. Arsenic exposure was assessed in toenail clippings. The analysis included 880 cases of BCC, 666 cases of SCC, and 780 controls. Results: There was an increased BCC risk associated with high arsenic exposure among those homozygous variant for XPA [odds ratio (OR) = 1.8; 95% confidence interval (CI), 0.9–3.7]. For XPD, having variation at both loci (312Asn and 751Gln) occurred less frequently among BCC and SCC cases compared with controls (OR = 0.8; 95% CI, 0.6–1.0) for both case groups. In the stratum of subjects who have variant for both XPD polymorphisms, there was a 2-fold increased risk of SCC associated with elevated arsenic (OR = 2.2; 95% CI, 1.0–5.0). The test for interaction between XPD and arsenic in SCC was of borderline significance (p < 0.07, 3 degrees of freedom). Conclusions: Our findings indicate a reduced NMSC risk in relation to XPD Asp312Asn and Lys751Gln variants. Further, these data support the hypothesis that NER polymorphisms may modify the association between NMSC and arsenic

Academic-community partnerships improve outcomes in pediatric trauma care

BackgroundTo address the specialized needs of injured children, pediatric trauma centers (PTCs) were established at many large, academic hospitals. This study explores clinical outcomes observed for injured children treated at an academic-sponsored community facility.MethodsIn partnership with an academic medical center in a major metropolitan area, a not-for-profit community hospital became a designated Level II PTC in October 2010. Data for injured children &lt;15 years old treated prior to PTC designation from January 2000 to September 2010 were prospectively collected using the Trauma and Emergency Medicine Information System and compared to data collected after PTC designation from January 2011 to December 2013.ResultsOverall, 681 injured children were treated at the community hospital from January 2011 to December 2013. Children treated after PTC designation were less likely to undergo computed tomography (CT) (50.9% vs. 81.3%, p&lt;0.01), even when controlling for age, gender, injury type, injury severity, and year (OR 0.18, 95%CI 0.08-0.37). Specifically, fewer head (45.7% vs. 68.7%, p&lt;0.01) and abdominal CTs (13.2% vs. 26.5%, p&lt;0.01) were performed. Hospital length of stay was significantly shorter (2.8 ± 3.7 days vs. 3.7 ± 5.9 days, p&lt;0.01). Mortality was low overall, but also decreased after PTC designation (0.4% vs. 2.0%, p=0.02).ConclusionsThese results indicate that academic-community partnerships in pediatric trauma care are a feasible alternative and may lead to improved outcomes for injured children

The Effect of Occupational Exposures to Animals on the Prevalence and Evidence of Leptospirosis

Background: The disease leptospirosis is one of the deadliest zoonotic illnesses worldwide and has been understudied in occupational populations who regularly work with animals. Previous studies have focused on weather and climate related exposures, neglecting this working population. Objective: The Navigation Guide methodology was used to conduct a systematic literature review to determine if there is increased prevalence of leptospirosis or seroprevalence indicating previous infection in occupationally exposed animal professions. Methods: By following the Navigation Guide procedures, we identified a specific study question and systematically evaluated the literature for inclusion in the final review. The 14 studies that were included subsequently underwent evaluation for risk of bias, quality, and strength of the evidence. Discussion: Due to issues with non-uniform presentation of the results among the included studies, cross study comparisons were made sparingly. Factors influencing the odds of contracting Leptospirosis included; smoking OR 14.4 (1.39, 134.74), consuming a liquid while working OR 5.1 (1.04, 24.30), washing hands after work OR 0.2 (0.03, 0.81), and using protective aprons OR 0.4 (0.2, 0.7). The annual prevalence of Leptospirosis ranged from 0.07-1.6 per 100,000 individuals. Occupation as the source of infection ranged from 30% to 88%. Studies had similar outcomes indicating increased prevalence/evidence of leptospirosis in occupational groups but these measures were not presented in an overly convincing manner. Conclusion: The quality of evidence was deemed moderate among the included studies and there was only “limited evidence” of an association between the occupationally exposed to animals population and increased prevalence of leptospirosis or leptospira antibody seropositivity. However, several factors were identified as either being protective or increasing the odds of contracting leptospirosis within this working population, and can subsequently serve as short term areas of intervention while more rigorous prospective research is conducted in the future

Toxic metals in private drinking well water and urinary tract outcomes in North Carolina

We investigated the association between levels of inorganic arsenic, cadmium, lead and manganese in private well water, incidence of bladder and kidney cancer and end stage renal disease [ESRD] prevalence in 100 counties in North Carolina, a state that has among the highest proportion of well water consumption in the country. Between 1998-2010, samples from private wells across counties were used to determine levels of inorganic arsenic, cadmium, lead and manganese (n=63,836, n=22,915, n=70,675 and n=65,535 measurements, respectively) and geocoded. Bladder and kidney cancer incidence for each county between 1990 and 2011 were obtained from the North Carolina Department of Health and Human Services. Prevalent cases of ESRD overall and subtypes were obtained from the US Renal Data System administrative data for all counties from 1991-2011. Counties with fewer than 11 cases or fewer than 10 well measurements for any metal were excluded from the analysis. County-level data on potential confounders were obtained from US Census Bureau data (2010) and the Behavioral Risk Factor Surveillance Study (2003, 2005). For each analyte, county-level mean concentration was calculated and divided into tertiles. We then used Poisson regression to estimate incidence rate ratio (IRR) for cancer outcomes and prevalence ratio (PR) for ESRD, 95% confidence interval (CI) between exposures and urinary tract outcomes, adjusting for age, gender, race, education, physical activity, smoking, diabetes, hypertension and residential well water supply using counties as the unit of analysis. Altogether, there were 24,989 kidney cancer and 34,270 bladder cancer cases and 2,76,091 ESRD cases. Elevated IRRs for kidney cancer were observed for both the 2nd tertile (0.60-0.98 ppb: IRR=1.07 (95% CI 1.03, 1.11)) and 3rd tertiles (0.99-11.44 ppb: IRR=1.06 (95% CI 1.01, 1.10)) of inorganic arsenic. For arsenic and ESRD, the 3rd tertile 0.99-11.44 ppb, vs. the 1st tertile (0.50-0.59 ppb), the prevalence risk was observed to be 1.05 (95% CI, 1.04, 1.07) for ESRD overall, and elevated for subtypes: 1.06 (95% CI: 1.03, 1.08) for diabetic nephropathy, 1.46 (95% CI: 1.42, 1.50) for hypertensive nephropathy, and 1.17 (95% CI: 1.13, 1.22) for glomerulonephritis. A dose response was observed for kidney and bladder cancer incidence in manganese exposure but not for ESRD and ESRD subtypes. Higher levels of cadmium and lead moderately increased the incidence risk of bladder cancer only. The conclusions are limited by the ecological approach, but the consistency of the associations suggests that the influence of metals, especially inorganic arsenic in private well water, on urinary tract outcomes deserves additional investigation

The Relationship Between Caregiving and Mortality After Accounting for Time-Varying Caregiver Status and Addressing the Healthy Caregiver Hypothesis.

BACKGROUND. Previous studies have shown inconsistent associations between caregiving and mortality. This may be due to analyzing caregiver status at baseline only, and that better health is probably related to taking on caregiving responsibilities and continuing in that role. The latter is termed The Healthy Caregiver Hypothesis, similar to the Healthy Worker Effect in occupational epidemiology. We applied common approaches from occupational epidemiology to evaluate the association between caregiving and mortality, including treating caregiving as time-varying and lagging exposure up to 5 years. METHODS. Caregiving status among 1,068 women (baseline mean age = 81.0 years; 35% caregivers) participating in the Caregiver-Study of Osteoporotic Fractures study was assessed at five interviews conducted between 1999 and 2009. Mortality was determined through January 2012. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals adjusted for sociodemographics, perceived stress, and functional limitations. RESULTS. A total of 483 participants died during follow-up (38.8% and 48.7% of baseline caregivers and noncaregivers, respectively). Using baseline caregiving status, the association with mortality was 0.77, 0.62–0.95. Models of time-varying caregiving status showed a more pronounced reduction in mortality in current caregivers (hazard ratios = 0.54, 0.38–0.75), which diminished with longer lag periods (3-year lag hazard ratio = 0.68, 0.52–0.88, 5-year lag hazard ratios = 0.76, 0.60–0.95). CONCLUSIONS. Overall, caregivers had lower mortality rates than noncaregivers in all analyses. These associations were sensitive to the lagged period, indicating that the timing of leaving caregiving does influence this relationship and should be considered in future investigations