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At least 19 records

Contextualizing Data Streams for Infectious Disease Surveillance

To aid in developing a global biosurveillance program, it is critical to develop a framework to capture and understand the myriad of data streams and evaluate them in context of surveillance goals. Toward this goal, Los Alamos National Laboratory has developed a new method of evaluating the effectiveness of data stream types through the use of a novel concept called the surveillance window, a technique that integrates operational systems analysis, surveillance system analysis and epidemiological analysis. This study provides a simple, yet elegant methodology for which to ground truth known and emerging data streams for utility in integrated biosurveillance efforts.

59 BASIC BIOLOGICAL SCIENCES↗

Shared Dosimetry Error in Epidemiological Dose-Response Analyses

Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of "possible" dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. Use of these methods for several studies, including the Mayak Worker Cohort and the U.S. Atomic Veterans Study, is discussed.

epidemiological analysis↗

Cadmium and atherosclerosis: A review of toxicological mechanisms and a meta-analysis of epidemiologic studies

Cadmium has been proposed to be the one of the factors of atherosclerosis development, although the existing data are still controversial. The primary objective of the present study is the review and the meta-analysis of studies demonstrating the association between Cd exposure and atherosclerosis as well as review of the potential mechanisms of such association. We performed a systematic search in the PubMed-Medline database using the MeSH terms cadmium, cardiovascular disease, atherosclerosis, coronary artery disease, myocardial infarction, stroke, mortality and humans up through December 20, 2017. Elevated urinary Cd levels were associated with increased mortality for cardiovascular disease (HR = 1.34, 95% CI: 1.07–1.67) as well as elevated blood Cd levels (HR = 1.78, 95% CI: 1.24–2.56). Analysis restricted to never smokers showed similar, though more imprecise, results. Consistently, we also observed an association between Cd exposure markers (blood and urine) and coronary heart disease, stroke, and peripheral artery disease. Moreover, Cd exposure was associated with atherogenic changes in lipid profile. High Cd exposure was associated with higher TC levels (OR = 1.48, 95% CI: 1.10–2.01), higher LDL-C levels (OR = 1.31, 95% CI 0.99–1.73) and lower HDL-C levels (OR = 1.96, 95% CI: 1.09–3.55). The mechanisms of atherogenic effect of cadmium may involve oxidative stress, inflammation, endothelial dysfunction, enhanced lipid synthesis, up-regulation of adhesion molecules, prostanoid dysbalance, as well as altered glycosaminoglycan synthesis.

54 ENVIRONMENTAL SCIENCES↗

Outbreak investigations of foot and mouth disease virus in Nepal between 2010 and 2015 in the context of historical serotype occurrence

Abstract Foot and Mouth Disease ( FMD ) is endemic in Nepal and causes substantial economic losses in the livestock industry. The goal of this study was to perform an epidemiological analysis of FMD outbreaks reported to the Veterinary Epidemiology Center, Tripureshwor, Nepal during 2010–2015, in order to strengthen the National FMD Control Program. These current data were considered in the context of historical data on FMD virus ( FMDV ) serotypes detected in the country between 1965 and 2015. During 2010–2015, a total of 1333 livestock holdings reported FMD outbreaks in Nepal. On average, 71.2 animals were affected in each outbreak, with a case fatality rate of 3.6%. FMD was reported throughout the country, and the proportion of affected holdings was not significantly among eco‐zones, regions, or species. The Hill eco‐zone had the highest number of holdings affected (782), followed by Mountain (304), and Terai (247). When analysed by the developmental region, the Western (381) and Central (368) Developmental Regions had the highest numbers of holdings affected. Cattle were the most frequently affected species (39%), followed by buffalo (33%), and goats (19%). FMD occurred throughout the year, with peaks in winter (December/January) and in the pre‐monsoon period (April/May). Between 1965 and 2015 FMDV serotype O had the highest prevalence (81%), followed by Asia‐1 (11%), A (6%), and C (2%). Serotype C was not detected after 1996, and only serotype O was reported after 2011. These descriptive analyses provide critical landmarks to establish baselines, and document early progress of the ongoing Progressive Control Pathway of FMD ( PCP ‐ FMD ) which could be useful in Nepal and other South Asian nations.

59 BASIC BIOLOGICAL SCIENCES↗

Short-term ozone exposure and asthma severity: Weight-of-evidence analysis

Highlights: • Evidence from multiple realms is integrated in the weight-of-evidence analysis. • Epidemiology suggests exacerbation events are associated with ambient ozone. • Experimental human and animal studies show pulmonary effects with high exposure. • The relevance of animal toxicity studies to human asthma is uncertain. • Evidence for causality between ambient ozone and asthma is {sup e}quipoise and above.” To determine whether evidence indicates that short-term exposure to ambient concentrations of ozone in the United States can affect asthma severity, we systematically reviewed published controlled human exposure, epidemiology, and animal toxicity studies. The strongest evidence for a potential causal relationship came from epidemiology studies reporting increased emergency department visits and hospital admissions for asthma following elevated ambient ozone concentrations. However, while controlled exposure studies reported lung function decrements and increased asthma symptoms following high ozone exposures 160–400 parts per billion [ppb]), epidemiology studies evaluating similar outcomes reported less consistent results. Animal studies showed changes in pulmonary function at high ozone concentrations (> 500 ppb), although there is substantial uncertainty regarding the relevance of these animal models to human asthma. Taken together, the weight of evidence indicates that there is at least an equal likelihood that either explanation is true, i.e., the strength of the evidence for a causal relationship between short-term exposure to ambient ozone concentrations and asthma severity is ''equipoise and above''.

54 ENVIRONMENTAL SCIENCES↗

Regional patterns of genetic diversity in swine influenza A viruses in the United States from 2010 to 2016

Background Regular spatial and temporal analyses of the genetic diversity and evolutionary patterns of influenza A virus (IAV) in swine inform control efforts and improve animal health. Initiated in 2009, the USDA passively surveils IAV in U.S. swine, with a focus on subtyping clinical respiratory submissions, sequencing the hemagglutinin (HA) and neuraminidase (NA) genes at a minimum, and sharing these data publicly. Objectives In this study, our goal was to quantify and describe regional and national patterns in the genetic diversity and evolution of IAV in U.S. swine from 2010 to 2016. Methods A comprehensive phylogenetic and epidemiological analysis of publicly available HA and NA genes generated by the USDA surveillance system collected from January 2010 to December 2016 was conducted. Results The dominant subtypes and genetic clades detected during the study period were H1N1 (H1-γ/1A.3.3.3, N1-classical, 29%), H1N2 (H1-δ1/1B.2.2, N2-2002, 27%), and H3N2 (H3-IV-A, N2-2002, 15%), but many other minor clades were also maintained. Year-round circulation was observed, with a primary epidemic peak in October-November and a secondary epidemic peak in March-April. Partitioning these data into 5 spatial zones revealed that genetic diversity varied regionally and was not correlated with aggregated national patterns of HA/NA diversity. Conclusions These data suggest that vaccine composition and control efforts should consider IAV diversity within swine production regions in addition to aggregated national patterns.

Infectious Diseases↗

Epidemiology, Clinical Features, and Outcomes of Coccidioidomycosis, Utah, 2006–2015

On the basis of a 1957 geographic Coccidioides seropositivity survey, 3 counties in southwestern Utah, USA, were considered coccidioidomycosis-endemic, but there has been a paucity of information on the disease burden in Utah since. We report findings from a recent clinical and epidemiologic study of coccidioidomycosis in Utah. To describe clinical characteristics, we identified all coccidioidomycosis cases in an integrated health system in the state during 2006–2015. For epidemiologic analysis, we used cases reported to the Utah Department of Health during 2009–2015. Mean state incidence was 1.83 cases/100,000 population/year. Washington County, in southwestern Utah, had the highest incidence, 17.2 cases/100,000 population/year. In a generalized linear model with time as a fixed effect, mean annual temperature, population, and new construction were associated with regional variations in incidence. Using these variables in a spatiotemporal model, we estimated the adjusted regional variation by county to predict areas where Coccidioides infections might increase.

60 APPLIED LIFE SCIENCES↗

Tea consumption and risk of bladder cancer in the Bladder Cancer Epidemiology and Nutritional Determinants (BLEND) Study: Pooled analysis of 12 international cohort studies

Tea has been shown to be associated with reduced risk of several diseases including cardiovascular diseases, stroke, metabolic syndrome, and obesity. However, the results on the relationship between tea consumption and bladder cancer are conflicting. This research aimed to assess the association between tea consumption and risk of bladder cancer using a pooled analysis of prospective cohort data. Individual data from 532,949 participants in 12 cohort studies, were pooled for analyses. Cox regression models stratified by study centre was used to estimate hazard ratios (HR) and corresponding 95% CIs. Fractional polynomial regression models were used to examine the dose–response relationship. A higher level of tea consumption was associated with lower risk of bladder cancer incidence (compared with no tea consumption: HR = 0.87, 95% C.I. = 0.77–0.98 for low consumption; HR = 0.86, 95% C.I. = 0.77–0.96 for moderate consumption; HR = 0.84, 95% C.I. = 0.75–0.95 for high consumption). When stratified by sex and smoking status, this reduced risk was statistically significant among men and current and former smokers. In addition, dose–response analyses showed a lower bladder cancer risk with increment of 100 ml of tea consumption per day (HR-increment = 0.97; 95% CI = 0.96–0.98). A similar inverse association was found among males, current and former smokers while never smokers and females showed non-significant results, suggesting potential sex-dependent effect. Higher consumption of tea is associated with reduced risk of bladder cancer with potential interaction with sex and smoking status. Further studies are needed to clarify the mechanisms for a protective effect of tea (e.g. inhibition of the survival and proliferation of cancer cells and anti-inflammatory mechanisms) and its interaction with smoking and sex.

60 APPLIED LIFE SCIENCES↗

Protecting Privacy of Shared Epidemiologic Data without Compromising Analysis Potential

Objective . Ensuring privacy of research subjects when epidemiologic data are shared with outside collaborators involves masking (modifying) the data, but overmasking can compromise utility (analysis potential). Methods of statistical disclosure control for protecting privacy may be impractical for individual researchers involved in small-scale collaborations. Methods . We investigated a simple approach based on measures of disclosure risk and analytical utility that are straightforward for epidemiologic researchers to derive. The method is illustrated using data from the Japanese Atomic-bomb Survivor population. Results . Masking by modest rounding did not adequately enhance security but rounding to remove several digits of relative accuracy effectively reduced the risk of identification without substantially reducing utility. Grouping or adding random noise led to noticeable bias. Conclusions . When sharing epidemiologic data, it is recommended that masking be performed using rounding. Specific treatment should be determined separately in individual situations after consideration of the disclosure risks and analysis needs.

Cologne, John↗

HIV-1 Transmission during Early Infection in Men Who Have Sex with Men: A Phylodynamic Analysis

Conventional epidemiological surveillance of infectious diseases is focused on characterization of incident infections and estimation of the number of prevalent infections. Advances in methods for the analysis of the population-level genetic variation of viruses can potentially provide information about donors, not just recipients, of infection. Genetic sequences from many viruses are increasingly abundant, especially HIV, which is routinely sequenced for surveillance of drug resistance mutations. In this study, we conducted a phylodynamic analysis of HIV genetic sequence data and surveillance data from a US population of men who have sex with men (MSM) and estimated incidence and transmission rates by stage of infection.

59 BASIC BIOLOGICAL SCIENCES↗

Computational epidemiological tools for pandemic analysis, understanding, and response

This suite of software tools is being developed to enhance and analyze computational epidemiological models that incorporate realistic disease dynamics and human behavior, with the goal of supporting epidemic and pandemic response. Specifically, the tools enable data analysis, feature extraction, data synthesis, machine learning model development, and prediction of key public health outcomes, such as cases, hospitalizations, deaths, and behavioral responses, for airborne infectious diseases like COVID-19 and influenza.

Butts, David↗

Survival Outcomes in Resected Extrahepatic Cholangiocarcinoma: Effect of Adjuvant Radiotherapy in a Surveillance, Epidemiology, and End Results Analysis

Purpose: The benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic cholangiocarcinoma has not been clearly established. We analyzed survival outcomes of patients with resected extrahepatic cholangiocarcinoma and examined the effect of adjuvant RT. Methods and Materials: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2003. The primary endpoint was the overall survival time. Cox regression analysis was used to perform univariate and multivariate analyses of the following clinical variables: age, year of diagnosis, histologic grade, localized (Stage T1-T2) vs. regional (Stage T3 or greater and/or node positive) stage, gender, race, and the use of adjuvant RT after surgical resection. Results: The records for 2,332 patients were obtained. Patients with previous malignancy, distant disease, incomplete or conflicting records, atypical histologic features, and those treated with preoperative/intraoperative RT were excluded. Of the remaining 1,491 patients eligible for analysis, 473 (32%) had undergone adjuvant RT. After a median follow-up of 27 months (among surviving patients), the median overall survival time for the entire cohort was 20 months. Patients with localized and regional disease had a median survival time of 33 and 18 months, respectively (p < .001). The addition of adjuvant RT was not associated with an improvement in overall or cause-specific survival for patients with local or regional disease. Conclusion: Patients with localized disease had significantly better overall survival than those with regional disease. Adjuvant RT was not associated with an improvement in long-term overall survival in patients with resected extrahepatic bile duct cancer. Key data, including margin status and the use of combined chemotherapy, was not available through the SEER database.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Management of Male Breast Cancer in the United States: A Surveillance, Epidemiology and End Results Analysis

Purpose: To analyze the stage-specific management of male breast cancer (MBC) with surgery and radiation therapy (RT) and relate them to outcomes and to female breast cancer (FBC). Methods and Materials: The Surveillance, Epidemiology, and End Results database was queried for all primary invasive MBC and FBC diagnosed from 1973 to 2008. Analyzable data included age, race, registry, grade, stage, estrogen and progesterone receptor status, type of surgery, and use of RT. Stage was defined as localized (LocD): confined to the breast; regional (RegD): involving skin, chest wall, and/or regional lymph nodes; and distant: M1. The primary endpoint was cause-specific survival (CSS). Results: A total of 4276 cases of MBC and 718,587 cases of FBC were identified. Male breast cancer constituted 0.6% of all breast cancer. Comparing MBC with FBC, mastectomy (M) was used in 87.4% versus 38.3%, and breast-conserving surgery in 12.6% versus 52.6% (P<10{sup −4}). For males with LocD, CSS was not significantly different for the 4.6% treated with lumpectomy/RT versus the 70% treated with M alone (hazard ratio [HR] 1.33; 95% confidence interval [CI] 0.49-3.61; P=.57). Postmastectomy RT was delivered in 33% of males with RegD and was not associated with an improvement in CSS (HR 1.11; 95% CI 0.88-1.41; P=.37). There was a significant increase in the use of postmastectomy RT in MBC over time: 24.3%, 27.2%, and 36.8% for 1973-1987, 1988-1997, and 1998-2008, respectively (P<.0001). Cause-specific survival for MBC has improved: the largest significant change was identified for men diagnosed in 1998-2008 compared with 1973-1987 (HR 0.73; 95% CI 0.60-0.88; P=.0004). Conclusions: Surgical management of MBC is dramatically different than for FBC. The majority of males with LocD receive M despite equivalent CSS with lumpectomy/RT. Postmastectomy RT is greatly underutilized in MBC with RegD, although a CSS benefit was not demonstrated. Outcomes for MBC are improving, attributable to improved therapy and its use in this unscreened population.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Non-Rhabdomyosarcoma Soft Tissue Sarcomas in Children: A Surveillance, Epidemiology, and End Results Analysis Validating COG Risk Stratifications

Purpose: Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) are a heterogeneous group of sarcomas that encompass over 35 histologies. With an incidence of ∼500 cases per year in the United States in those <20 years of age, NRSTS are rare and therefore difficult to study in pediatric populations. We used the large Surveillance, Epidemiology, and End Results (SEER) database to validate the prognostic ability of the Children's Oncology Group (COG) risk classification system and to define patient, tumor, and treatment characteristics. Methods and Materials: From SEER data from 1988 to 2007, we identified patients ≤18 years of age with NRSTS. Data for age, sex, year of diagnosis, race, registry, histology, grade, primary size, primary site, stage, radiation therapy, and survival outcomes were analyzed. Patients with nonmetastatic grossly resected low-grade tumors of any size or high-grade tumors ≤5 cm were considered low risk. Cases of nonmetastatic tumors that were high grade, >5 cm, or unresectable were considered intermediate risk. Patients with nodal or distant metastases were considered high risk. Results: A total of 941 patients met the review criteria. On univariate analysis, black race, malignant peripheral nerve sheath (MPNST) histology, tumors >5 cm, nonextremity primary, lymph node involvement, radiation therapy, and higher risk group were associated with significantly worse overall survival (OS) and cancer-specific survival (CSS). On multivariate analysis, MPNST histology, chemotherapy-resistant histology, and higher risk group were significantly poor prognostic factors for OS and CSS. Compared to low-risk patients, intermediate patients showed poorer OS (hazard ratio [HR]: 6.08, 95% confidence interval [CI]: 3.53-10.47, P<.001) and CSS (HR: 6.27; 95% CI: 3.44-11.43, P<.001), and high-risk patients had the worst OS (HR: 13.35, 95% CI: 8.18-21.76, P<.001) and CSS (HR: 14.65, 95% CI: 8.49-25.28, P<.001). Conclusions: The current COG risk group stratification for children with NRSTS has been validated with a large number of children in the SEER database.

62 RADIOLOGY AND NUCLEAR MEDICINE↗