Association of community types and features in a case-control analysis of new onset type 2 diabetes across a diverse geography in Pennsylvania.

OBJECTIVES: To evaluate associations of community types and features with new onset type 2 diabetes in diverse communities. Understanding the location and scale of geographic disparities can lead to community-level interventions. DESIGN: Nested case-control study within the open dynamic cohort of health system patients. SETTING: Large, integrated health system in 37 counties in central and northeastern Pennsylvania, USA. PARTICIPANTS AND ANALYSIS: We used electronic health records to identify persons with new-onset type 2 diabetes from 2008 to 2016 (n=15 888). Persons with diabetes were age, sex and year matched (1:5) to persons without diabetes (n=79 435). We used generalised estimating equations to control for individual-level confounding variables, accounting for clustering of persons within communities. Communities were defined as (1) townships, boroughs and city census tracts; (2) urbanised area (large metro), urban cluster (small cities and towns) and rural; (3) combination of the first two; and (4) county. Community socioeconomic deprivation and greenness were evaluated alone and in models stratified by community types. RESULTS: Borough and city census tract residence (vs townships) were associated (OR (95% CI)) with higher odds of type 2 diabetes (1.10 (1.04 to 1.16) and 1.34 (1.25 to 1.44), respectively). Urbanised areas (vs rural) also had increased odds of type 2 diabetes (1.14 (1.08 to 1.21)). In the combined definition, the strongest associations (vs townships in rural areas) were city census tracts in urban clusters (1.41 (1.22 to 1.62)) and city census tracts in urbanised areas (1.33 (1.22 to 1.45)). Higher community socioeconomic deprivation and lower greenness were each associated with increased odds. CONCLUSIONS: Urban residence was associated with higher odds of type 2 diabetes than for other areas. Higher community socioeconomic deprivation in city census tracts and lower greenness in all community types were also associated with type 2 diabetes.

Longitudinal evaluation of clustering of chronic sinonasal and related symptoms using exploratory factor analysis.

BACKGROUND: Sinonasal symptoms are common and can have several underlying causes. When symptoms occur in specified patterns lasting 3 months or more they meet criteria for chronic rhinosinusitis (CRS). Approaches to CRS symptom measurement do not specify how to measure symptoms and treat specified sinonasal symptoms as generally interchangeable, suggesting that such symptoms should cluster on 1 or 2 latent factors. METHODS: We used questionnaire responses to 37 questions on the presence, severity, bother, and frequency of cardinal sinonasal and related symptoms lasting 3 months, from 3535 subjects at 3 time points over 16 months. We completed 5 exploratory factor analyses (EFA) to identify symptom clustering, 1 for each time point and 2 for the differences between adjacent questionnaires. The baseline EFA was used to provide factor scores that were described longitudinally and examined by CRS status. RESULTS: Five EFAs identified the same 5 factors (blockage and discharge, pain and pressure, asthma and cold/flu symptoms, smell loss, and ear and eye [mainly allergy] symptoms), with clustering determined by symptom frequency, severity, and degree of bother. Responses to individual questions showed changes over time but when combined into factor scores showed less longitudinal change. All symptom factor scores were progressively higher from never to past to current CRS status. CONCLUSIONS: Although the current approaches to symptom characterization in CRS imply a single underlying latent construct, our results suggest that there are at least 3 latent constructs relevant to CRS. Further studies are needed to evaluate whether these clusters have identifiable underlying pathobiologies.

Prevalence, severity, and risk factors for acute exacerbations of nasal and sinus symptoms by chronic rhinosinusitis status.

BACKGROUND: Nasal and sinus symptoms (NSS) are common to many health conditions, including chronic rhinosinusitis (CRS). Few studies have investigated the occurrence and severity of, and risk factors for, acute exacerbations of NSS (AENSS) by CRS status (current, past, or never met European Position Paper on Rhinosinusitis [EPOS] criteria for CRS). METHODS: Four seasonal questionnaires were mailed to a stratified random sample of Geisinger primary care patients. Logistic regression was used to identify individual characteristics associated with AENSS occurrence and severity by CRS status (current long-term, current recent, past, never) using EPOS subjective symptoms-only (EPOSS ) CRS criteria. We operationalized 3 AENSS definitions based on prescribed antibiotics or oral corticosteroids, symptoms, and symptoms with purulence. RESULTS: Baseline and at least 1 follow-up questionnaires were available from 4736 subjects. Self-reported NSS severity with exacerbation was worst in the current long-term CRS group. AENSS was common in all subgroups examined and generally more common among those with current EPOSS CRS. Seasonal prevalence of AENSS differed by AENSS definition and CRS status. Associations of risk factors with AENSS differed by definition, but CRS status, body mass index, asthma, hay fever, sinus surgery history, and winter season consistently predicted AENSS. CONCLUSIONS: In this first longitudinal, population-based study of 3 AENSS definitions, NSS and AENSS were both common, sometimes severe, and differed by EPOSS CRS status. Contrasting associations of risk factors for AENSS by the different definitions suggest a need for a standardized approach to definition of AENSS.

Early-life antibiotic use and subsequent diagnosis of food allergy and allergic diseases.

BACKGROUND: Antibiotic use in early life has been linked to disruptions in the microbiome. Such changes can disturb immune system development. Differences have been observed in the microbiota of children with and without allergies, but there have been few studies on antibiotic use and allergic disease. OBJECTIVE: We evaluated associations of early-life antibiotic use with subsequent occurrence of food allergy and other allergies in childhood using electronic health record data. METHODS: We used longitudinal data on 30 060 children up to age 7 years from Geisinger Clinic's electronic health record to conduct a sex- and age-matched case-control study to evaluate the association between antibiotic use and milk allergy, non-milk food allergies, and other allergies. For each outcome, we estimated conditional logistic regression models adjusting for race/ethnicity, history of Medical Assistance, and mode of birth delivery. Models were repeated separately for penicillins, cephalosporins and macrolides. RESULTS: There were 484 milk allergy cases, 598 non-milk food allergy cases and 3652 other allergy cases. Children with three or more antibiotic orders had a greater odds of milk allergy (Odds Ratio; 95% Confidence interval) (1.78; 1.28-2.48), non-milk food allergy (1.65; 1.27-2.14), and other allergies (3.07; 2.72-3.46) compared with children with no antibiotic orders. Associations were strongest at younger ages and differed by antibiotic class. CONCLUSIONS AND CLINICAL RELEVANCE: We observed associations between antibiotic orders and allergic diseases, providing evidence of a potentially modifiable clinical practice associated with paediatric allergic disease. Differences by antibiotic class should be further explored, as this knowledge could inform paediatric treatment decisions.

Nasal and sinus symptoms and chronic rhinosinusitis in a population-based sample.

BACKGROUND: The objective of this study was to describe the first US-based study to use the European Position Paper on Rhinosinusitis (EPOS) criteria to study the prevalence of chronic rhinosinusitis (CRS) in a general-population sample. METHODS: A CRS symptom questionnaire was mailed to 23 700 primary care patients from Geisinger Clinic, a health system serving 45 counties in Pennsylvania. CRS cases were categorized into four unique subgroups based on EPOS symptoms: obstruction and discharge with no smell loss or pain/pressure; smell loss without pain/pressure; facial pain and/or pressure without smell loss; and both smell loss and pain/pressure. All cases were required to have nasal obstruction or discharge. Logistic regression was used to evaluate potential factors associated with CRS subgroups. RESULTS: We found that 11.9% of patients met criteria for CRS. Prevalence peaked at 15.9% between ages 50 and 59 years and then dropped to 6.8% after age 69. The odds of CRS was higher among patients who were white, younger, smokers, had a history of Medical Assistance, and had other diseases. When CRS subgroups were modeled separately, these associations were no longer significant for some CRS subgroups. Comorbid diseases were most strongly associated with CRS cases who reported smell loss and facial pain and/or pressure and had the weakest associations with CRS cases who did not report these symptoms. CONCLUSIONS: CRS is a highly prevalent and heterogeneous condition. Differences in risk factors and health outcomes across symptom subgroups may be indicative of differences in etiology that have implications for disease management.

Antibiotic use and childhood body mass index trajectory.

BACKGROUND/OBJECTIVES: Antibiotics are commonly prescribed for children. Use of antibiotics early in life has been linked to weight gain but there are no large-scale, population-based, longitudinal studies of the full age range among mainly healthy children. SUBJECTS/METHODS: We used electronic health record data on 163 820 children aged 3-18 years and mixed effects linear regression to model associations of antibiotic orders with growth curve trajectories of annual body mass index (BMI) controlling for confounders. Models evaluated three kinds of antibiotic associations-reversible (time-varying indicator for an order in year before each BMI), persistent (time-varying cumulative orders up to BMIj) and progressive (cumulative orders up to prior BMI (BMIj-1))-and whether these varied by age. RESULTS: Among 142 824 children under care in the prior year, a reversible association was observed and this short-term BMI gain was modified by age (P<0.001); effect size peaked in mid-teen years. A persistent association was observed and this association was stronger with increasing age (P<0.001). The addition of the progressive association among children with at least three BMIs (n=79 752) revealed that higher cumulative orders were associated with progressive weight gain; this did not vary by age. Among children with an antibiotic order in the prior year and at least seven lifetime orders, antibiotics (all classes combined) were associated with an average weight gain of approximately 1.4 kg at age 15 years. When antibiotic classes were evaluated separately, the largest weight gain at 15 years was associated with macrolide use. CONCLUSIONS: We found evidence of reversible, persistent and progressive effects of antibiotic use on BMI trajectories, with different effects by age, among mainly healthy children. The results suggest that antibiotic use may influence weight gain throughout childhood and not just during the earliest years as has been the primary focus of most prior studies.

Five-year risk of incident disease following a diagnosis of chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) has a broad range of comorbidities. Due to a lack of longitudinal studies, it is not known whether these comorbidities cause CRS, are promoted by CRS, or share a systemic disease process with CRS. OBJECTIVE: The objective of this study was to determine the risk of incident disease within 5 years after a new diagnosis of CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP). METHODS: We conducted a case-control study nested within the longitudinal cohort of primary care patients in the Geisinger Clinic using electronic health record data. We evaluated incident disease over 5 years in newly diagnosed CRSwNP and CRSsNP cases compared to controls using multivariable Cox regression models. RESULTS: CRSsNP (n = 3612) cases were at greater risk (HR, 95% confidence interval) than controls for incidence of: upper airway diseases, including adenotonsillitis (3.29, 2.41-4.50); lower aerodigestive tract diseases, including asthma (2.69, 2.14-3.38); epithelial conditions, including atopic dermatitis (2.75, 1.23-6.16); and hypertension (1.38, 1.19-1.61). CRSwNP (n = 241) cases were at greater risk for obesity than controls (1.74, 1.08-2.80), but CRSwNP was not associated with other diseases. CONCLUSION: The risk of other diseases associated with CRS adds to the burden of an already highly burdensome condition, and suggests either that CRS promotes onset of other diseases or is an indicator of systemic disease processes. Different patterns of association with diseases by CRS phenotype may be due to CRSwNP sample size limitations or reflect a different pattern of disease onset by phenotype. These findings have implications for screening guidelines and care of CRS patients.

Considerations for screening live kidney donors for endemic infections: a viewpoint on the UNOS policy.

In February 2013, the Organ Procurement and Transplantation Network mandated that transplant centers perform screening of living kidney donors prior to transplantation for Strongyloides, Trypanosoma cruzi and West Nile virus (WNV) infection if the donor is from an endemic area. However, specific guidelines for screening were not provided, such as the optimal testing modalities, timing of screening prior to donation and the appropriate selection of donors. In this regard, the American Society of Transplantation Infectious Diseases Community of Practice, together with disease-specific experts, has developed this viewpoint document to provide guidance for the testing of live donors for Strongyloides, T. cruzi and WNV infection, specifically identifying at-risk populations and testing algorithms, including advantages, limitations and interpretation of results.

Scedosporium prolificans pericarditis and mycotic aortic aneurysm in a lung transplant recipient receiving voriconazole prophylaxis.

Despite the adoption of antifungal prophylaxis, fungal infections remain a significant concern in lung transplant recipients. Indeed, some concern exists that such prophylaxis may increase the risk of infection with drug-resistant fungal organisms. Here, we describe a case of disseminated Scedosporium prolificans infection, presenting as pericarditis, which developed in a lung transplant patient receiving prophylactic voriconazole for 8 months. The epidemiology and clinical presentation of S. prolificans infections are reviewed, and controversies surrounding antifungal prophylaxis and the development of resistant infections are discussed.

A population-based study of the epidemiology and clinical features of methicillin-resistant Staphylococcus aureus infection in Pennsylvania, 2001-2010.

No U.S. general population-based study has characterized the epidemiology and risk factors, including skin and soft tissue infection (SSTI), for healthcare-associated (HA) and community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA). We estimated the incidence of HA- and CA-MRSA and SSTI over a 9-year period using electronic health record data from the Geisinger Clinic in Pennsylvania. MRSA cases were frequency-matched to SSTI cases and controls in a nested case-control analysis. Logistic regression was used to assess risk factors, while accounting for antibiotic administration. We identified 1713 incident CA- and 1506 HA-MRSA cases and 78 216 SSTI cases. On average, from 2005 to 2009, the annual incidence of CA-MRSA increased by 34%, HA-MRSA by 7%, and SSTI by 4%. Age, season, community socioeconomic deprivation, obesity, smoking, previous SSTI, and antibiotic administration were identified as independent risk factors for CA-MRSA.

Diagnosis and management of tuberculosis in transplant donors: a donor-derived infections consensus conference report.

Mycobacterium tuberculosis is a ubiquitous organism that infects one-third of the world's population. In previous decades, access to organ transplantation was restricted to academic medical centers in more developed, low tuberculosis (TB) incidence countries. Globalization, changing immigration patterns, and the expansion of sophisticated medical procedures to medium and high TB incidence countries have made tuberculosis an increasingly important posttransplant infectious disease. Tuberculosis is now one of the most common bacterial causes of solid-organ transplant donor-derived infection reported in transplant recipients in the United States. Recognition of latent or undiagnosed active TB in the potential organ donor is critical to prevent emergence of disease in the recipient posttransplant. Donor-derived tuberculosis after transplantation is associated with significant morbidity and mortality, which can best be prevented through careful screening and targeted treatment. To address this growing challenge and provide recommendations, an expert international working group was assembled including specialists in transplant infectious diseases, transplant surgery, organ procurement and TB epidemiology, diagnostics and management. This working group reviewed the currently available data to formulate consensus recommendations for screening and management of TB in organ donors.

Organ donor screening practices for Trypanosoma cruzi infection among US Organ Procurement Organizations.

Donor-derived Trypanosoma cruzi infection in solid organ transplant recipients is associated with significant morbidity and mortality. Little is known about T. cruzi screening practices among U.S. organ procurement organizations (OPOs). We distributed a questionnaire to all U.S. OPO directors, requesting data on T. cruzi screening strategies, laboratory methods, number of donors screened, disposition of organs from positive donors and attitudes toward screening. Fifty-eight (100%) U.S. OPOs responded to the survey. Donor screening began in 2002 and is presently performed by 11 (19%) OPOs. Among screening OPOs, four screen all donors and seven use a risk-based strategy. Three different T. cruzi serology tests are used for donor screening. During 2008, 9/993 (0.9%) donors screened positive by a T. cruzi screening test, 6/9 (66%) had confirmatory tests performed and 4/6 (66%) had positive confirmatory tests. These results led to the nonuse of five donors and 17 organs. Five organs from three seropositive donors were transplanted in 2008 without recognized disease transmission. Variability of T. cruzi donor screening strategies, laboratory methods and disposition of organs from positive donors currently exists. Further research is needed to identify the risk of donor-derived T. cruzi infections to help inform the best screening strategy.

Screening and treatment of chagas disease in organ transplant recipients in the United States: recommendations from the chagas in transplant working group.

Donor-derived transmission of Trypanosoma cruzi, the etiologic agent of Chagas disease, has emerged as an issue in the United States over the past 10 years. Acute T. cruzi infection causes substantial morbidity and mortality in the posttransplant setting if not recognized and treated early. We assembled a working group of transplant infectious disease specialists, laboratory medicine specialists, organ procurement organization representatives and epidemiologists with expertise in Chagas disease. Based on review of published and unpublished data, the working group prepared evidence-based recommendations for donor screening, and follow-up testing and treatment of recipients of organs from infected donors. We advise targeted T. cruzi screening of potential donors born in Mexico, Central America and South America. Programs can consider transplantation of kidneys and livers from T. cruzi-infected donors with informed consent from recipients. However, we recommend against heart transplantation from infected donors. For other organs, we recommend caution based on the anticipated degree of immunosuppression. Our recommendations stress the need for systematic monitoring of recipients by polymerase chain reaction, and microscopy of buffy coat and advance planning for immediate antitrypanosomal treatment if recipient infection is detected. Data on management and outcomes of all cases should be collected to inform future guidelines and to assist in coordination with public health authorities.

Environmental lead exposure and cognitive function in community-dwelling older adults.

OBJECTIVE: To determine if long-term exposure to high levels of lead in the environment is associated with decrements in cognitive ability in older Americans. METHODS: We completed a cross-sectional analysis using multiple linear regression to evaluate associations of recent (in blood) and cumulative (in tibia) lead dose with cognitive function in 991 sociodemographically diverse, community-dwelling adults, aged 50 to 70 years, randomly selected from 65 contiguous neighborhoods in Baltimore, MD. Tibia lead was measured with (109)Cd induced K-shell X-ray fluorescence. Seven summary measures of cognitive function were created based on standard tests in these domains: language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, visual memory, and visuoconstruction. RESULTS: The mean (SD) blood lead level was 3.5 (2.2) microg/dL and tibia lead level was 18.7 (11.2) microg/g. Higher tibia lead levels were consistently associated with worse cognitive function in all seven domains after adjusting for age, sex, APOE-epsilon4, and testing technician (six domains p

Past adult lead exposure is linked to neurodegeneration measured by brain MRI.

OBJECTIVE: To determine whether cumulative lead dose in former organolead workers was associated with MRI measures of white matter lesions (WML) and global and structure-specific brain volumes. METHODS: MRIs, tibia lead, and other measures were obtained from 532 former organolead workers with a mean age of 56 years and a mean of 18 years since last occupational exposure to lead. Cumulative lead dose was measured by tibia lead, obtained by X-ray fluorescence, and expressed as microg lead per gram of bone mineral (microg Pb/g). WML were evaluated using the Cardiovascular Health Study grading scale. A total of 21 global and specific brain regions were evaluated. RESULTS: A total of 36% of individuals had WML grade of 1 to 7 (0 to 9 scale). Increasing peak tibia lead was associated with increasing WML grade (p = 0.004). The adjusted OR for a 1 microg Pb/g increase in tibia lead was 1.042 (95% CI = 1.021, 1.063) for a CHS grade of 5+ (> or = 5 vs < 5). In linear regression, the coefficient for tibia lead was negative for associations with all structures. Higher tibia lead was significantly related to smaller total brain volume, frontal and total gray matter volume, and parietal white matter volume. Of nine smaller specific regions of interest, higher tibia lead was associated with smaller volumes for the cingulate gyrus and insula. CONCLUSIONS: These data suggest that cumulative lead dose is associated with persistent brain lesions, and may explain previous findings of a progressive decline in cognitive function.

Associations of lead biomarkers with renal function in Korean lead workers.

AIMS: To compare associations of lead biomarkers with renal function in current and former lead workers. METHODS: Cross sectional analysis of first year results from a longitudinal study of 803 lead workers and 135 controls in South Korea. Clinical renal function was assessed by blood urea nitrogen (BUN), serum creatinine, and measured and calculated creatinine clearance. Urinary N-acetyl-beta-D-glucosaminidase (NAG) and retinol-binding protein were also measured. RESULTS: Mean (SD) tibia lead, blood lead, and DMSA chelatable lead levels in lead workers were 37.2 (40.4) micro g/g bone mineral, 32.0 (15.0) micro g/dl, and 767.8 (862.1) micro g/g creatinine, respectively. Higher lead measures were associated with worse renal function in 16/42 models. When influential outliers were removed, higher lead measures remained associated with worse renal function in nine models. An additional five associations were in the opposite direction. Effect modification by age was observed. In 3/16 models, associations between higher lead measures and worse clinical renal function in participants in the oldest age tertile were significantly different from associations in those in the youngest age tertile which were in the opposite direction. Mean urinary cadmium (CdU) was 1.1 micro g/g creatinine (n = 191). Higher CdU levels were associated with higher NAG. CONCLUSIONS: These data suggest that lead has an adverse effect on renal function in the moderate dose range, particularly in older workers. Associations between higher lead measures and lower BUN and serum creatinine and higher creatinine clearances may represent lead induced hyperfiltration. Environmental cadmium may also have an adverse renal impact, at least on NAG.

Occupational risk of Lyme disease: an epidemiological review.

Lyme disease is the most common vector borne disease in the United States. Since the early 1980s, a large body of literature has evaluated the occupational risk of Lyme disease. The availability of a new vaccine to prevent Lyme disease makes it necessary for occupational health professionals to make decisions regarding the occupational risk of the disease among employees.

Associations of lead exposure and dose measures with erythrocyte protein kinase C activity in 212 current Korean lead workers.

Lead can replace calcium in enzyme assays that measure protein kinase C activity and lead activates protein kinase C in human erythrocytes after exposure to lead in vitro. To examine the relevance of these observations to lead exposure in humans, we studied the associations of lead found in blood or tibia with activation of protein kinase C in erythrocytes isolated from workers in the lead industry. We examined erythrocytes among 212 lead workers, with a mean (+/-SD) age of 39.1 (10.0) years and exposure duration of 8.1 (6.5) years and measured protein kinase C activation by an in vitro back-phosphorylation assay. After adjustment for potential confounding factors (age and sex), tibia lead and exposure duration were significantly associated with erythrocyte protein kinase C activation (both p values < 0.05). No associations were observed between protein kinase C activation and blood-lead or zinc-protoporphyrin levels. These findings suggest that human exposure to lead results in activation of erythrocyte protein kinase C, which may be directly relevant to the neurotoxicity of lead.