Sample records for large population-based case-control

  1. Assessment of TREM2 rs75932628 association with Alzheimer's disease in a population-based sample: the Cache County Study.

    PubMed

    Gonzalez Murcia, Josue D; Schmutz, Cameron; Munger, Caitlin; Perkes, Ammon; Gustin, Aaron; Peterson, Michael; Ebbert, Mark T W; Norton, Maria C; Tschanz, Joann T; Munger, Ronald G; Corcoran, Christopher D; Kauwe, John S K

    2013-12-01

    Recent studies have identified the rs75932628 (R47H) variant in TREM2 as an Alzheimer's disease risk factor with estimated odds ratio ranging from 2.9 to 5.1. The Cache County Memory Study is a large, population-based sample designed for the study of memory and aging. We genotyped R47H in 2974 samples (427 cases and 2540 control subjects) from the Cache County study using a custom TaqMan assay. We observed 7 heterozygous cases and 12 heterozygous control subjects with an odds ratio of 3.5 (95% confidence interval, 1.3-8.8; p = 0.0076). The minor allele frequency and population attributable fraction for R47H were 0.0029 and 0.004, respectively. This study replicates the association between R47H and Alzheimer's disease risk in a large, population-based sample, and estimates the population frequency and attributable risk of this rare variant. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Birth outcomes of male and female patients with infantile hypertrophic pyloric stenosis--a population-based case-control study.

    PubMed

    Vermes, Gabor; Mátrai, Ákos; Czeizel, Andrew E; Ács, Nándor

    2016-01-01

    Most of the patients are affected by isolated infantile hypertrophic pyloric stenosis (IHPS) beyond the polygenic predisposition, the other factors in the multifactorial etiology are largely unknown. The main characteristic of IHPS is the robust male predominance, thus the aim of this study was to analyze birth outcomes in males and females whether they are different or not. The study samples included 241 cases with IHPS, 357 matched, and 38,151 population controls without any defect in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. The findings of this case-control study confirmed the well-known strong male excess (85.5%). The mean gestational age was somewhat longer and it is associated with a lower rate of preterm births. Mean birth weight did not show significant differences among the study groups, but the rate of low birthweight was higher in cases with IHPS. However, these differences were found only in males. Thus, intrauterine fetal growth restriction is characteristic only for male cases with IHPS. Our study confirmed the well-known obvious male excess of cases with IHPS, but our findings suggest some differences in birth outcomes of male and female cases. Male cases with IHPS had intrauterine fetal growth restriction while females did not. These data may indicate some differences in the pathogenesis of IHPS in males and females.

  3. Combining matched and unmatched control groups in case-control studies.

    PubMed

    le Cessie, Saskia; Nagelkerke, Nico; Rosendaal, Frits R; van Stralen, Karlijn J; Pomp, Elisabeth R; van Houwelingen, Hans C

    2008-11-15

    Multiple control groups in case-control studies are used to control for different sources of confounding. For example, cases can be contrasted with matched controls to adjust for multiple genetic or unknown lifestyle factors and simultaneously contrasted with an unmatched population-based control group. Inclusion of different control groups for a single exposure analysis yields several estimates of the odds ratio, all using only part of the data. Here the authors introduce an easy way to combine odds ratios from several case-control analyses with the same cases. The approach is based upon methods used for meta-analysis but takes into account the fact that the same cases are used and that the estimated odds ratios are therefore correlated. Two ways of estimating this correlation are discussed: sandwich methodology and the bootstrap. Confidence intervals for the pooled estimates and a test for checking whether the odds ratios in the separate case-control studies differ significantly are derived. The performance of the method is studied by simulation and by applying the methods to a large study on risk factors for thrombosis, the MEGA Study (1999-2004), wherein cases with first venous thrombosis were included with a matched control group of partners and an unmatched population-based control group.

  4. Risk factors for pneumonic and ulceroglandular tularaemia in Finland: a population-based case-control study.

    PubMed

    Rossow, H; Ollgren, J; Klemets, P; Pietarinen, I; Saikku, J; Pekkanen, E; Nikkari, S; Syrjälä, H; Kuusi, M; Nuorti, J P

    2014-10-01

    Few population-based data are available on factors associated with pneumonic and ulceroglandular type B tularaemia. We conducted a case-control study during a large epidemic in 2000. Laboratory-confirmed case patients were identified through active surveillance and matched control subjects (age, sex, residency) from the national population information system. Data were collected using a self-administered questionnaire. A conditional logistic regression model addressing missing data with Bayesian full-likelihood modelling included 227 case patients and 415 control subjects; reported mosquito bites [adjusted odds ratio (aOR) 9·2, 95% confidence interval (CI) 4·4-22, population-attributable risk (PAR) 82%] and farming activities (aOR 4·3, 95% CI 2·5-7·2, PAR 32%) were independently associated with ulceroglandular tularaemia, whereas exposure to hay dust (aOR 6·6, 95% CI 1·9-25·4, PAR 48%) was associated with pneumonic tularaemia. Although the bulk of tularaemia type B disease burden is attributable to mosquito bites, risk factors for ulceroglandular and pneumonic forms of tularaemia are different, enabling targeting of prevention efforts accordingly.

  5. Birth outcomes of cases with conotruncal defects of heart - a population-based case-control study.

    PubMed

    Vereczkey, Attila; Kósa, Zsolt; Csáky-Szunyogh, Melinda; Gerencsér, Balázs; Czeizel, Andrew E

    2015-03-01

    The aim of this study was to evaluate the birth outcomes of cases with four types of conotruncal defects (CTDs), i.e. common truncus, transposition of great arteries, tetralogy of Fallot and double-outlet right ventricle. Birth outcomes of 597 live-born cases with CTD and 38,151 population controls without any defects were compared in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities completed by socio-demographic variables of their mothers. There was a male excess in cases with CTD (56.8%) with the same mean gestational age (39.4 versus 39.4 weeks) and preterm birth rate (8.2 versus 9.2%), but their mean birth weight was smaller (3077 versus 3276 g) with a high rate of low birthweight (14.6 versus 5.7%) compared to the birth outcomes of population controls. These data indicate intrauterine growth restriction of fetuses affected with transposition of great arteries, tetralogy of Fallot and double-outlet right ventricle particularly in females, while there were a shorter mean gestational age and smaller mean birth weigh in cases with common truncus. In general CTD, except common truncus, had no effect for gestational age but associated with a high risk for intrauterine fetal growth restriction particularly in female cases.

  6. Maternal characteristics and birth outcomes of pregnant women who had offspring with congenital ear abnormalities - a population-based case-control study.

    PubMed

    Paput, László; Bánhidy, Ferenc; Czeizel, Andrew E

    2011-09-01

    To describe the maternal characteristics and birth outcomes of newborn infants affected with isolated ear congenital abnormalities (IECA), mainly isolated anotia/microtia and unclassified multiple congenital abnormalities (CAs) including anotia/microtia (UMAM). Cases with IECA and UMAM were compared with their matched controls and all controls without any defect and malformed controls affected with other defects in the population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities. The mothers of 354 cases with IECA did not show significant difference in age, but their mean birth order was higher while their socio-economic status based on the maternal employment status was lower compared to the figures of their matched controls. There was a male excess among cases with microtia and mainly with UMAM. The evaluation of birth outcomes of newborns affected with IECA indicated intrauterine fetal growth retardation. Newborn infants with isolated microtia had intrauterine growth retardation and the association of this developmental defect localized for a small region of head with the general fetal development raises interesting theoretical question.

  7. Hyperthyroidism and erectile dysfunction: a population-based case-control study.

    PubMed

    Keller, J; Chen, Y-K; Lin, H-C

    2012-01-01

    Dysthyroidism has been highlighted as a common endocrine disorder associated with erectile dysfunction (ED); however, to date, no large-scale population-based study has investigated the association between hyperthyroidism and ED. This case-control study aimed to explore the association between ED and hyperthyroidism using a population-based data set. In total, 6310 adult patients who received new diagnoses of ED were recruited as cases together with 18 930 matched enrollees with no history of ED who served as controls. Conditional logistic regressions were conducted to explore the association between ED and having been previously diagnosed with hyperthyroidism. In total, 569 (2.3%) of the 25 240 sampled subjects had been diagnosed with hyperthyroidism before the index date; hyperthyroidism was found in 207 (3.3%) cases and 362 (1.90%) controls. After adjusting for potential confounding factors, the odds ratio (OR) of prior hyperthyroidism among cases was 1.64 (95% confidence interval=1.37-1.96, P<0.001) than that of controls. No association was detected between prior hyperthyroidism and ED for the 18-30, 30-39 and >70 age groups. Subjects aged between 60 and 69 years had the highest ORs for prior hyperthyroidism among cases when compared to controls (OR=1.84; 95% confidence interval=1.20-2.84; P<0.001). Our study further confirms the existence of an association between ED and prior hyperthyroidism.

  8. Pooled Resequencing of 122 Ulcerative Colitis Genes in a Large Dutch Cohort Suggests Population-Specific Associations of Rare Variants in MUC2.

    PubMed

    Visschedijk, Marijn C; Alberts, Rudi; Mucha, Soren; Deelen, Patrick; de Jong, Dirk J; Pierik, Marieke; Spekhorst, Lieke M; Imhann, Floris; van der Meulen-de Jong, Andrea E; van der Woude, C Janneke; van Bodegraven, Adriaan A; Oldenburg, Bas; Löwenberg, Mark; Dijkstra, Gerard; Ellinghaus, David; Schreiber, Stefan; Wijmenga, Cisca; Rivas, Manuel A; Franke, Andre; van Diemen, Cleo C; Weersma, Rinse K

    2016-01-01

    Genome-wide association studies have revealed several common genetic risk variants for ulcerative colitis (UC). However, little is known about the contribution of rare, large effect genetic variants to UC susceptibility. In this study, we performed a deep targeted re-sequencing of 122 genes in Dutch UC patients in order to investigate the contribution of rare variants to the genetic susceptibility to UC. The selection of genes consists of 111 established human UC susceptibility genes and 11 genes that lead to spontaneous colitis when knocked-out in mice. In addition, we sequenced the promoter regions of 45 genes where known variants exert cis-eQTL-effects. Targeted pooled re-sequencing was performed on DNA of 790 Dutch UC cases. The Genome of the Netherlands project provided sequence data of 500 healthy controls. After quality control and prioritization based on allele frequency and pathogenicity probability, follow-up genotyping of 171 rare variants was performed on 1021 Dutch UC cases and 1166 Dutch controls. Single-variant association and gene-based analyses identified an association of rare variants in the MUC2 gene with UC. The associated variants in the Dutch population could not be replicated in a German replication cohort (1026 UC cases, 3532 controls). In conclusion, this study has identified a putative role for MUC2 on UC susceptibility in the Dutch population and suggests a population-specific contribution of rare variants to UC.

  9. Calcium and vitamin D and risk of colorectal cancer: results from a large population-based case-control study in Newfoundland and Labrador and Ontario.

    PubMed

    Sun, Zhuoyu; Wang, Peizhong Peter; Roebothan, Barbara; Cotterchio, Michelle; Green, Roger; Buehler, Sharon; Zhao, Jinhui; Squires, Josh; Zhao, Jing; Zhu, Yun; Dicks, Elizabeth; Campbell, Peter T; Mclaughlin, John R; Parfrey, Patrick S

    2011-01-01

    Previous epidemiological studies have been suggestive but inconclusive in demonstrating inverse associations of calcium, vitamin D, dairy product intakes with risk of colorectal cancer (CRC). We conducted a large population-based comparison of such associations in Newfoundland and Labrador (NL) and Ontario (ON). A case control study design was used. Colorectal cancer cases were new CRC patients aged 20-74 years. Controls were a sex and age-group matched random sample of the population in each province. 1760 cases and 2481 controls from NL and ON were analyzed. Information on dietary intake and lifestyle was collected using self-administered food frequency and personal history questionnaires. Controls reported higher mean daily intakes of total calcium and total vitamin D than cases in both provinces. In ON, significant reduced CRC risk was associated with intakes of total calcium (OR of highest vs. lowest quintiles was 0.57, 95% CI 0.42-0.77, p(trend) = 0.03), total vitamin D (OR = 0.73, 95% CI 0.54-1.00), dietary calcium (OR = 0.76, 95% CI 0.60-0.97), dietary vitamin D (OR = 0.77, 95% CI 0.61-0.99), total dairy products and milk (OR = 0.78, 95% CI 0.60-1.00), calcium-containing supplements use (OR = 0.76). In NL, the inverse associations of calcium, vitamin D with CRC risk were most pronounced among calcium- or vitamin D-containing supplement users (OR = 0.67, 0.68, respectively). Results of this study add to the evidence that total calcium, dietary calcium, total vitamin D, dietary vitamin D, calcium- or vitamin D-containing supplement use may reduce the risk of CRC. The inverse associations of CRC risk with intakes of total dairy products and milk may be largely due to calcium and vitamin D.

  10. Vaccines for Conservation: Plague, Prairie Dogs & Black-Footed Ferrets as a Case Study.

    PubMed

    Salkeld, Daniel J

    2017-09-01

    The endangered black-footed ferret (Mustela nigripes) is affected by plague, caused by Yersinia pestis, both directly, as a cause of mortality, and indirectly, because of the impacts of plague on its prairie dog (Cynomys spp.) prey base. Recent developments in vaccines and vaccine delivery have raised the possibility of plague control in prairie dog populations, thereby protecting ferret populations. A large-scale experimental investigation across the western US shows that sylvatic plague vaccine delivered in oral baits can increase prairie dog survival. In northern Colorado, an examination of the efficacy of insecticides to control fleas and plague vaccine shows that timing and method of plague control is important, with different implications for long-term and large-scale management of Y. pestis delivery. In both cases, the studies show that ambitious field-work and cross-sectoral collaboration can provide potential solutions to difficult issues of wildlife management, conservation and disease ecology.

  11. A case-control study of the association between ulcerative colitis and hyperthyroidism in an Asian population.

    PubMed

    Tsai, Ming-Chieh; Lin, Herng-Ching; Lee, Cha-Ze

    2017-06-01

    Ulcerative colitis (UC) is a chronic relapsing inflammatory disease with significant clinical diversity. However, the aetiology, pathogenesis and optimal treatment of UC remain unclear. The purpose of this case-control study was to investigate the association between previously diagnosed hyperthyroidism and UC using a large population-based data set in Taiwan. The data for this population-based case-control study were retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We included 2709 patients with UC as cases and 8127 sex- and age-matched patients without UC as controls. A conditional logistic regression analysis was conducted to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between UC and prior hyperthyroidism. We found that, in total, 327 of the 10 836 sampled patients (3.02%) had previously been diagnosed with hyperthyroidism. There was a higher proportion of prior hyperthyroidism among cases than controls (4.10% vs 2.66%, P<.001). A conditional logistic regression showed that the OR of prior hyperthyroidism was 1.57 (95% CI=1.24-1.98) compared to controls. Similarly, after adjusting for monthly income, geographic location and urbanization level, cases were still more likely to have previously been diagnosed with hyperthyroidism than controls (OR=1.61, 95% CI=1.27-2.05). Furthermore, we analysed the ORs of prior hyperthyroidism between cases and controls according to age group. We found that of the youngest group of sampled patients (18-39 years), cases had the greatest adjusted OR for having previously been diagnosed with hyperthyroidism than controls (OR=1.98, 95% CI=1.04-3.79). This study demonstrated an association between UC and hyperthyroidism. © 2017 John Wiley & Sons Ltd.

  12. Association of young and advanced age of pregnant women with the risk of isolated congenital abnormalities in Hungary - a population-based case-matched control study.

    PubMed

    Csermely, Gyula; Susánszky, Éva; Czeizel, Andrew E

    2015-03-01

    To analyze the possible association of maternal age with the risk of all congenital abnormalities (CAs) in a population-based large case-matched control data set. The Hungarian Case-Control Surveillance of Congenital Abnormalities included 21,494 cases with isolated CA and their 34,311 matched controls. First the distribution of maternal age groups in 24 CA-groups and their matched controls was compared. In the second step, young (19 years or less) and advanced (35 years or more) age groups were compared. Finally, the subgroups of neural-tube defects, congenital heart defects and abdominal wall's CA were evaluated separately. A higher risk of gastroschisis, congenital heart defects, particularly left-sided obstructive defects, undescended testis and clubfoot was found in the youngest age group (19 years or less) of cases. The higher proportion of pregnant women with advanced age (i.e. 35 years or more) showed only a borderline excess in cases with clubfoot. The so-called U-shaped risk of maternal age distribution was found in cases with clubfoot and in the total group of isolated CAs. The maternal age is a contributing factor to the origin of some isolated CAs mainly in young pregnant women.

  13. Childhood leukaemia and distance from power lines in California: a population-based case-control study.

    PubMed

    Crespi, Catherine M; Vergara, Ximena P; Hooper, Chris; Oksuzyan, Sona; Wu, Sheng; Cockburn, Myles; Kheifets, Leeka

    2016-06-28

    Studies have reported an increased risk of childhood leukaemia associated with living near high-voltage electric power transmission lines that extend to distances at which magnetic fields from lines are negligible. We conducted a large records-based case-control study of childhood leukaemia risk in the population living near power lines in California. The study included 5788 childhood leukaemia and 3308 central nervous system (CNS) cancer cases (for comparison) born in and diagnosed in California (1986-2008), and matched to population-based controls by age and sex. We geocoded birth address and estimated the distance from residence to transmission lines using geographic information systems, aerial imagery, and, for some residences, site visits. For leukaemia, there was a slight excess of cases within 50 m of a transmission line over 200 kV (odds ratio 1.4, 95% confidence interval 0.7-2.7). There was no evidence of increased risk for distances beyond 50 m, for lower-voltage lines, or for CNS cancers. Our findings did not clearly support an increased childhood leukaemia risk associated with close proximity (<50 m) to higher voltage lines, but could be consistent with a small increased risk. Reports of increased risk for distances beyond 50 m were not replicated.

  14. Environment And Genetics in Lung cancer Etiology (EAGLE) study: an integrative population-based case-control study of lung cancer.

    PubMed

    Landi, Maria Teresa; Consonni, Dario; Rotunno, Melissa; Bergen, Andrew W; Goldstein, Alisa M; Lubin, Jay H; Goldin, Lynn; Alavanja, Michael; Morgan, Glen; Subar, Amy F; Linnoila, Ilona; Previdi, Fabrizio; Corno, Massimo; Rubagotti, Maurizia; Marinelli, Barbara; Albetti, Benedetta; Colombi, Antonio; Tucker, Margaret; Wacholder, Sholom; Pesatori, Angela C; Caporaso, Neil E; Bertazzi, Pier Alberto

    2008-06-06

    Lung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease. We designed a large population-based case-control study that combines a traditional molecular epidemiology design with a more integrative approach to investigate the dynamic process that begins with smoking initiation, proceeds through dependency/smoking persistence, continues with lung cancer development and ends with progression to disseminated disease or response to therapy and survival. The study allows the integration of data from multiple sources in the same subjects (risk factors, germline variation, genomic alterations in tumors, and clinical endpoints) to tackle the disease etiology from different angles. Before beginning the study, we conducted a phone survey and pilot investigations to identify the best approach to ensure an acceptable participation in the study from cases and controls. Between 2002 and 2005, we enrolled 2101 incident primary lung cancer cases and 2120 population controls, with 86.6% and 72.4% participation rate, respectively, from a catchment area including 216 municipalities in the Lombardy region of Italy. Lung cancer cases were enrolled in 13 hospitals and population controls were randomly sampled from the area to match the cases by age, gender and residence. Detailed epidemiological information and biospecimens were collected from each participant, and clinical data and tissue specimens from the cases. Collection of follow-up data on treatment and survival is ongoing. EAGLE is a new population-based case-control study that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer outcome, through examination of epidemiological, molecular, and clinical data. We have provided a detailed description of the study design, field activities, management, and opportunities for research following this integrative approach, which allows a sharper and more comprehensive vision of the complex nature of this disease. The study is poised to accelerate the emergence of new preventive and therapeutic strategies with potentially enormous impact on public health.

  15. Lung Cancer and Occupation in a Population-based Case-Control Study

    PubMed Central

    Consonni, Dario; De Matteis, Sara; Lubin, Jay H.; Wacholder, Sholom; Tucker, Margaret; Pesatori, Angela Cecilia; Caporaso, Neil E.; Bertazzi, Pier Alberto; Landi, Maria Teresa

    2010-01-01

    The authors examined the relation between occupation and lung cancer in the large, population-based Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study. In 2002–2005 in the Lombardy region of northern Italy, 2,100 incident lung cancer cases and 2,120 randomly selected population controls were enrolled. Lifetime occupational histories (industry and job title) were coded by using standard international classifications and were translated into occupations known (list A) or suspected (list B) to be associated with lung cancer. Smoking-adjusted odds ratios and 95% confidence intervals were calculated with logistic regression. For men, an increased risk was found for list A (177 exposed cases and 100 controls; odds ratio = 1.74, 95% confidence interval: 1.27, 2.38) and most occupations therein. No overall excess was found for list B with the exception of filling station attendants and bus and truck drivers (men) and launderers and dry cleaners (women). The authors estimated that 4.9% (95% confidence interval: 2.0, 7.8) of lung cancers in men were attributable to occupation. Among those in other occupations, risk excesses were found for metal workers, barbers and hairdressers, and other motor vehicle drivers. These results indicate that past exposure to occupational carcinogens remains an important determinant of lung cancer occurrence. PMID:20047975

  16. The Mortality Penalty of Incarceration: Evidence from a Population-based Case-control Study of Working-age Males.

    PubMed

    Pridemore, William Alex

    2014-06-01

    There is a growing body of research on the effects of incarceration on health, though there are few studies in the sociological literature of the association between incarceration and premature mortality. This study examined the risk of male premature mortality associated with incarceration. Data came from the Izhevsk (Russia) Family Study, a large-scale population-based case-control design. Cases (n = 1,750) were male deaths aged 25 to 54 in Izhevsk between October 2003 and October 2005. Controls (n = 1,750) were selected at random from a city population register. The key independent variable was lifetime prevalence of incarceration. I used logistic regression to estimate mortality odds ratios, controlling for age, hazardous drinking, smoking status, marital status, and education. Seventeen percent of cases and 5 percent of controls had been incarcerated. Men who had been incarcerated were more than twice as likely as those who had not to experience premature mortality (odds ratio = 2.2, 95 percent confidence interval: 1.6-3.0). Relative to cases with no prior incarceration, cases who had been incarcerated were more likely to die from infectious diseases, respiratory diseases, non-alcohol-related accidental poisonings, and homicide. Taken together with other recent research, these results from a rigorous case-control design reveal not only that incarceration has durable effects on illness, but that its consequences extend to a greater risk of early death. I draw on the sociology of health literature on exposure, stress, and social integration to speculate about the reasons for this mortality penalty of incarceration. © American Sociological Association 2014.

  17. Investigation of occupational and environmental causes of respiratory cancers (ICARE): a multicenter, population-based case-control study in France.

    PubMed

    Luce, Danièle; Stücker, Isabelle

    2011-12-14

    Occupational causes of respiratory cancers need to be further investigated: the role of occupational exposures in the aetiology of head and neck cancers remains largely unknown, and there are still substantial uncertainties for a number of suspected lung carcinogens. The main objective of the study is to examine occupational risk factors for lung and head and neck cancers. ICARE is a multi-center, population-based case-control study, which included a group of 2926 lung cancer cases, a group of 2415 head and neck cancer cases, and a common control group of 3555 subjects. Incident cases were identified in collaboration with cancer registries, in 10 geographical areas. The control group was a random sample of the population of these areas, with a distribution by sex and age comparable to that of the cases, and a distribution by socioeconomic status comparable to that of the population. Subjects were interviewed face to face, using a standardized questionnaire collecting particularly information on tobacco and alcohol consumption, residential history and a detailed description of occupational history. Biological samples were also collected from study subjects. The main occupational exposures of interest are asbestos, man-made mineral fibers, formaldehyde, polycyclic aromatic hydrocarbons, chromium and nickel compounds, arsenic, wood dust, textile dust, solvents, strong acids, cutting fluids, silica, diesel fumes, welding fumes. The complete list of exposures of interest includes more than 60 substances. Occupational exposure assessment will use several complementary methods: case-by-case evaluation of exposure by experts; development and use of algorithms to assess exposure from the questionnaires; application of job-exposure matrices. The large number of subjects should allow to uncover exposures associated with moderate increase in risks, and to evaluate risks associated with infrequent or widely dispersed exposures. It will be possible to study joint effects of exposure to different occupational risk factors, to examine the interactions between occupational exposures, tobacco smoking, alcohol drinking, and genetic risk factors, and to estimate the proportion of respiratory cancers attributable to occupational exposures in France. In addition, information on many non-occupational risk factors is available, and the study will provide an excellent framework for numerous studies in various fields.

  18. ALS and the Military: A Population-Based Study in the Danish Registries

    PubMed Central

    Seals, Ryan M.; Kioumourtzoglou, Marianthi-Anna; Gredal, Ole; Hansen, Johnni; Weisskopf, Marc G.

    2016-01-01

    Background Prior studies have suggested that military service may be associated with the development of amyotrophic lateral sclerosis. We conducted a population-based case-control study in Denmark to assess whether occupation in the Danish military is associated with an increased risk of developing amyotrophic lateral sclerosis. Methods There were 3,650 incident cases of amyotrophic lateral sclerosis recorded in the Danish National Patient Registry between 1982 and 2009. Each case was matched to 100 age- and sex-matched population controls alive and free of amyotrophic lateral sclerosis on the date of the case diagnosis. Comprehensive occupational history was obtained from the Danish Pension Fund database, which began in 1964. Results 2.4% (n=8,922) of controls had a history of employment in the military prior to the index date. Military employees overall had an elevated rate of ALS (OR=1.3; 95% CI: 1.1-1.6). A ten-year increase in years employed by the military was associated with an odds ratio of 1.2 (95% CI: 1.0-1.4), and all quartiles of time employed were elevated. There was little suggestion of a pattern across calendar year of first employment, but there was some evidence that increasing age at first employment was associated with increased ALS rates. Rates were highest in the decade immediately following the end of employment (OR=1.6; 95% CI: 1.2-2.2). Conclusions In this large population-based case-control study, employment by the military is associated with increased rates of ALS. These findings are consistent with earlier findings that military service or employment may entail exposure to risk factors for ALS. PMID:26583610

  19. Childhood leukaemia and distance from power lines in California: a population-based case-control study

    PubMed Central

    Crespi, Catherine M; Vergara, Ximena P; Hooper, Chris; Oksuzyan, Sona; Wu, Sheng; Cockburn, Myles; Kheifets, Leeka

    2016-01-01

    Background: Studies have reported an increased risk of childhood leukaemia associated with living near high-voltage electric power transmission lines that extend to distances at which magnetic fields from lines are negligible. We conducted a large records-based case-control study of childhood leukaemia risk in the population living near power lines in California. Methods: The study included 5788 childhood leukaemia and 3308 central nervous system (CNS) cancer cases (for comparison) born in and diagnosed in California (1986–2008), and matched to population-based controls by age and sex. We geocoded birth address and estimated the distance from residence to transmission lines using geographic information systems, aerial imagery, and, for some residences, site visits. Results: For leukaemia, there was a slight excess of cases within 50 m of a transmission line over 200 kV (odds ratio 1.4, 95% confidence interval 0.7–2.7). There was no evidence of increased risk for distances beyond 50 m, for lower-voltage lines, or for CNS cancers. Conclusions: Our findings did not clearly support an increased childhood leukaemia risk associated with close proximity (<50 m) to higher voltage lines, but could be consistent with a small increased risk. Reports of increased risk for distances beyond 50 m were not replicated. PMID:27219016

  20. Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design.

    PubMed

    Castaño-Vinyals, Gemma; Aragonés, Nuria; Pérez-Gómez, Beatriz; Martín, Vicente; Llorca, Javier; Moreno, Victor; Altzibar, Jone M; Ardanaz, Eva; de Sanjosé, Sílvia; Jiménez-Moleón, José Juan; Tardón, Adonina; Alguacil, Juan; Peiró, Rosana; Marcos-Gragera, Rafael; Navarro, Carmen; Pollán, Marina; Kogevinas, Manolis

    2015-01-01

    We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  1. Does Exposure to Agricultural Chemicals Increase the Risk of Prostate Cancer among Farmers?

    PubMed Central

    Parent, Marie-Élise; Désy, Marie; Siemiatycki, Jack

    2009-01-01

    Several studies suggest that farmers may be at increased risk of prostate cancer. The present analysis, based on a large population-based case-control study conducted among men in the Montreal area in the early 1980’s, aim at identifying occupational chemicals which may be responsible for such increases. The original study enrolled 449 prostate cancer cases, nearly 4,000 patients with other cancers, as well as 533 population controls. Subjects were interviewed about their occupation histories, and a team of industrial hygienists assigned their past exposures using a checklist of some 300 chemicals. The present analysis was restricted to a study base of men who had worked as farmers earlier in their lives. There were a total of 49 men with prostate cancers, 127 with other cancers and 56 population controls. We created a pool of 183 controls combining the patients with cancers at sites other than the prostate and the population controls. We then estimated the odds ratio for prostate cancer associated with exposure to each of 10 agricultural chemicals, i.e., pesticides, arsenic compounds, acetic acid, gasoline engine emissions, diesel engine emissions, polycyclic aromatic hydrocarbons from petroleum, lubricating oils and greases, alkanes with ≥18 carbons, solvents, and mononuclear aromatic hydrocarbons. Based on a model adjusting for age, ethnicity, education, and respondent status, there was evidence of a two-fold excess risk of prostate cancer among farmers with substantial exposure to pesticides [odds ratio (OR)=2.3, 95% confidence interval (CI) 1.1–5.1], as compared to unexposed farmers. There was some suggestion, based on few subjects, of increased risks among farmers ever exposed to diesel engine emissions (OR=5.7, 95% CI 1.2–26.5). The results for pesticides are particularly noteworthy in the light of findings from previous studies. Suggestions of trends for elevated risks were noted with other agricultural chemicals, but these are largely novel and need further confirmation in larger samples. PMID:19753293

  2. Maximum likelihood estimation for Cox's regression model under nested case-control sampling.

    PubMed

    Scheike, Thomas H; Juul, Anders

    2004-04-01

    Nested case-control sampling is designed to reduce the costs of large cohort studies. It is important to estimate the parameters of interest as efficiently as possible. We present a new maximum likelihood estimator (MLE) for nested case-control sampling in the context of Cox's proportional hazards model. The MLE is computed by the EM-algorithm, which is easy to implement in the proportional hazards setting. Standard errors are estimated by a numerical profile likelihood approach based on EM aided differentiation. The work was motivated by a nested case-control study that hypothesized that insulin-like growth factor I was associated with ischemic heart disease. The study was based on a population of 3784 Danes and 231 cases of ischemic heart disease where controls were matched on age and gender. We illustrate the use of the MLE for these data and show how the maximum likelihood framework can be used to obtain information additional to the relative risk estimates of covariates.

  3. The potential value of sibling controls compared with population controls for association studies of lifestyle-related risk factors: an example from the Breast Cancer Family Registry.

    PubMed

    Milne, Roger L; John, Esther M; Knight, Julia A; Dite, Gillian S; Southey, Melissa C; Giles, Graham G; Apicella, Carmel; West, Dee W; Andrulis, Irene L; Whittemore, Alice S; Hopper, John L

    2011-10-01

    A previous Australian population-based breast cancer case-control study found indirect evidence that control participation, although high, was not random. We hypothesized that unaffected sisters may provide a more appropriate comparison group than unrelated population controls. Three population-based case-control-family studies of breast cancer in women of white European origin were carried out by the Australian, Ontario and Northern California sites of the Breast Cancer Family Registry. We compared risk factors between 3643 cases, 2444 of their unaffected sisters and 2877 population controls and conducted separate case-control analyses based on population and sister controls using unconditional multivariable logistic regression. Compared with sister controls, population controls were more highly educated, had an earlier age at menarche, fewer births, their first birth at a later age and their last birth more recently. The established breast cancer associations detected using sister controls, but not detected using population controls, were decreasing risk with each of later age at menarche, more births, younger age at first birth and greater time since last birth. Since participation of population controls might be unintentionally related to some risk factors, we hypothesize that sister controls could provide more valid relative risk estimates and be recruited at lower cost. Given declining study participation by population controls, this contention is highly relevant to epidemiologic research.

  4. Night work and breast cancer: a population-based case-control study in France (the CECILE study).

    PubMed

    Menegaux, Florence; Truong, Thérèse; Anger, Antoinette; Cordina-Duverger, Emilie; Lamkarkach, Farida; Arveux, Patrick; Kerbrat, Pierre; Févotte, Joëlle; Guénel, Pascal

    2013-02-15

    Night work involving disruption of circadian rhythm was suggested as a possible cause of breast cancer. We examined the role of night work in a large population-based case-control study carried out in France between 2005 and 2008. Lifetime occupational history including work schedules of each night work period was elicited in 1,232 cases of breast cancer and 1,317 population controls. Thirteen percent of the cases and 11% of the controls had ever worked on night shifts (OR = 1.27 [95% confidence interval = 0.99-1.64]). Odds ratios were 1.35 [1.01-1.80] in women who worked on overnight shifts, 1.40 [1.01-1.92] in women who had worked at night for 4.5 or more years, and 1.43 [1.01-2.03] in those who worked less than three nights per week on average. The odds ratio was 1.95 [1.13-3.35] in women employed in night work for >4 years before their first full-term pregnancy, a period where mammary gland cells are incompletely differentiated and possibly more susceptible to circadian disruption effects. Our results support the hypothesis that night work plays a role in breast cancer, particularly in women who started working at night before first full-term pregnancy. Copyright © 2012 UICC.

  5. [Design requirements for clinical trials on re-evaluation of safety and efficacy of post-marketed Chinese herbs].

    PubMed

    Xie, Yanming; Wei, Xu

    2011-10-01

    Re-evaluation of post-marketed based on pharmacoepidemiology is to study and collect clinical medicine safety in large population under practical applications for a long time. It is necessary to conduct re-evaluation of clinical effectiveness because of particularity of traditional Chinese medicine (TCM). Right before carrying out clinical trials on re-evaluation of post-marketed TCM, we should determine the objective of the study and progress it in the assessment mode of combination of disease and syndrome. Specical population, involving children and seniors who were excluded in pre-marketed clinical trial, were brought into drug monitoring. Sample size needs to comply with statistical requirement. We commonly use cohort study, case-control study, nested case-control, pragmatic randomized controlled trials.

  6. Evaluation of type 2 diabetes genetic risk variants in Chinese adults: findings from 93,000 individuals from the China Kadoorie Biobank.

    PubMed

    Gan, Wei; Walters, Robin G; Holmes, Michael V; Bragg, Fiona; Millwood, Iona Y; Banasik, Karina; Chen, Yiping; Du, Huaidong; Iona, Andri; Mahajan, Anubha; Yang, Ling; Bian, Zheng; Guo, Yu; Clarke, Robert J; Li, Liming; McCarthy, Mark I; Chen, Zhengming

    2016-07-01

    Genome-wide association studies (GWAS) have discovered many risk variants for type 2 diabetes. However, estimates of the contributions of risk variants to type 2 diabetes predisposition are often based on highly selected case-control samples, and reliable estimates of population-level effect sizes are missing, especially in non-European populations. The individual and cumulative effects of 59 established type 2 diabetes risk loci were measured in a population-based China Kadoorie Biobank (CKB) study of 93,000 Chinese adults, including >7,100 diabetes cases. Association signals were directionally consistent between CKB and the original discovery GWAS: of 56 variants passing quality control, 48 showed the same direction of effect (binomial test, p = 2.3 × 10(-8)). We observed a consistent overall trend towards lower risk variant effect sizes in CKB than in case-control samples of GWAS meta-analyses (mean 19-22% decrease in log odds, p ≤ 0.0048), likely to reflect correction of both 'winner's curse' and spectrum bias effects. The association with risk of diabetes of a genetic risk score, based on lead variants at 25 loci considered to act through beta cell function, demonstrated significant interactions with several measures of adiposity (BMI, waist circumference [WC], WHR and percentage body fat [PBF]; all p interaction < 1 × 10(-4)), with a greater effect being observed in leaner adults. Our study provides further evidence of shared genetic architecture for type 2 diabetes between Europeans and East Asians. It also indicates that even very large GWAS meta-analyses may be vulnerable to substantial inflation of effect size estimates, compared with those observed in large-scale population-based cohort studies. Details of how to access China Kadoorie Biobank data and details of the data release schedule are available from www.ckbiobank.org/site/Data+Access .

  7. Modeling and E-M estimation of haplotype-specific relative risks from genotype data for a case-control study of unrelated individuals.

    PubMed

    Stram, Daniel O; Leigh Pearce, Celeste; Bretsky, Phillip; Freedman, Matthew; Hirschhorn, Joel N; Altshuler, David; Kolonel, Laurence N; Henderson, Brian E; Thomas, Duncan C

    2003-01-01

    The US National Cancer Institute has recently sponsored the formation of a Cohort Consortium (http://2002.cancer.gov/scpgenes.htm) to facilitate the pooling of data on very large numbers of people, concerning the effects of genes and environment on cancer incidence. One likely goal of these efforts will be generate a large population-based case-control series for which a number of candidate genes will be investigated using SNP haplotype as well as genotype analysis. The goal of this paper is to outline the issues involved in choosing a method of estimating haplotype-specific risk estimates for such data that is technically appropriate and yet attractive to epidemiologists who are already comfortable with odds ratios and logistic regression. Our interest is to develop and evaluate extensions of methods, based on haplotype imputation, that have been recently described (Schaid et al., Am J Hum Genet, 2002, and Zaykin et al., Hum Hered, 2002) as providing score tests of the null hypothesis of no effect of SNP haplotypes upon risk, which may be used for more complex tasks, such as providing confidence intervals, and tests of equivalence of haplotype-specific risks in two or more separate populations. In order to do so we (1) develop a cohort approach towards odds ratio analysis by expanding the E-M algorithm to provide maximum likelihood estimates of haplotype-specific odds ratios as well as genotype frequencies; (2) show how to correct the cohort approach, to give essentially unbiased estimates for population-based or nested case-control studies by incorporating the probability of selection as a case or control into the likelihood, based on a simplified model of case and control selection, and (3) finally, in an example data set (CYP17 and breast cancer, from the Multiethnic Cohort Study) we compare likelihood-based confidence interval estimates from the two methods with each other, and with the use of the single-imputation approach of Zaykin et al. applied under both null and alternative hypotheses. We conclude that so long as haplotypes are well predicted by SNP genotypes (we use the Rh2 criteria of Stram et al. [1]) the differences between the three methods are very small and in particular that the single imputation method may be expected to work extremely well. Copyright 2003 S. Karger AG, Basel

  8. Distribution of maternal age and birth order groups in cases with unclassified multiple congenital abnormalities according to the number of component abnormalities: a national population-based case-control study.

    PubMed

    Csermely, Gyula; Czeizel, Andrew E; Veszprémi, Béla

    2015-02-01

    Multiple congenital abnormalities are caused by chromosomal aberrations, mutant major genes and teratogens. A minor proportion of these patients are identified as syndromes but the major part belonging to the group of unclassified multiple CAs (UMCAs). The main objective of this study was to evaluate the maternal age and birth order in pregnant women who had offspring affected with UMCA. The strong association between numerical chromosomal aberrations, e.g., Down syndrome and advanced maternal age is well-known and tested here. The Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980 to 1996, yielded a large population-based national data set with 22,843 malformed newborns or fetuses ("informative cases") included 1349 UMCA cases with their 2407 matched controls. Case-control comparison of maternal age and birth order was made for cases with UMCA, stratified by component numbers and their controls. In addition, 834 cases with Down syndrome were compared to 1432 matched controls. The well-known advanced maternal age with the higher risk for Down syndrome was confirmed. The findings of the study suggest that the young age of mothers associates with the higher risk of UMCA, in addition birth order 4 or more associates with the higher risk for UMCA with 2 and 3 component CAs. This study was the first to analyze the possible maternal and birth order effect for cases with UMCA, and the young age and higher birth order associated with a higher risk for UMCA. © 2014 Wiley Periodicals, Inc.

  9. Syphilis in the economic center of South China: results from a real-time, web-based surveillance program.

    PubMed

    Zhang, Wangjian; Du, Zhicheng; Tang, Shaokai; Guo, Pi; Ye, Xingdong; Hao, Yuantao

    2015-08-08

    Guangzhou is the economic center of South China, which is currently suffering an insidious re-emergence of syphilis. Syphilis epidemic in this area is a matter of serious concern, because of the special economic position of Guangzhou and its large migrant population. Therefore, a comprehensive analysis of surveillance data is needed to provide further information for developing targeted control programs. Case-based surveillance data obtained from a real-time, web-based system were analyzed. A hierarchical clustering method was applied to classify the 12 districts of Guangzhou into several epidemiological regions. The district-level annual incidence and clustering results were displayed on the same map to show the spatial patterns of syphilis in Guangzhou. A total of 60,178 syphilis cases were reported during the period from 2005 to 2013, among which primary/secondary syphilis accounted for 15,864 cases (26.36 %), latent syphilis for 41,078 cases (68.26 %) and congenital syphilis for 2,090 cases (3.47 %). Moreover, primary/secondary syphilis burden slightly decreased from 17.5-18.0 cases per 100,000 people in the first years to 10.6 cases per 100,000 in 2013, with latent syphilis largely increasing from 18.5 cases per 100,000 to 43.4 cases per 100,000. Districts of Guangzhou could be classified into 3 epidemiological regions according to the syphilis burden over the last 3 years of the study period. The burden of primary/secondary syphilis appears to be decreasing in recent years, whereas that of latent syphilis is increasing. Given the epidemiological features and the annual changes found in this study, it is suggested that future control programs should be more population-specific and spatially targeted.

  10. Investigation of established genetic risk variants for glioma in prediagnostic samples from a population-based nested case-control study.

    PubMed

    Wibom, Carl; Späth, Florentin; Dahlin, Anna M; Langseth, Hilde; Hovig, Eivind; Rajaraman, Preetha; Johannesen, Tom Børge; Andersson, Ulrika; Melin, Beatrice

    2015-05-01

    Although glioma etiology is poorly understood in general, growing evidence indicates a genetic component. Four large genome-wide association studies (GWAS) have linked common genetic variants with an increased glioma risk. However, to date, these studies are based largely on a case-control design, where cases have been recruited at the time of or after diagnosis. They may therefore suffer from a degree of survival bias, introduced when rapidly fatal cases are not included. To confirm glioma risk variants in a prospective setting, we have analyzed 11 previously identified risk variants in a set of prediagnostic serum samples with 598 cases and 595 matched controls. Serum samples were acquired from The Janus Serum Bank, a Norwegian population-based biobank reserved for cancer research. We confirmed the association with glioma risk for variants within five genomic regions: 8q24.21 (CCDC26), 9p21.3 (CDKN2B-AS1), 11q23.3 (PHLDB1), 17p13.1 (TP53), and 20q13.33 (RTEL1). However, previously identified risk variants within the 7p11.2 (EGFR) region were not confirmed by this study. Our results indicate that the risk variants that were confirmed by this study are truly associated with glioma risk and may, consequently, affect gliomagenesis. Though the lack of positive confirmation of EGFR risk variants may be attributable to relatively limited statistical power, it nevertheless raises the question whether they truly are risk variants or markers for glioma prognosis. Our findings indicate the need for further studies to clarify the role of glioma risk loci with respect to prolonged survival versus etiology. ©2015 American Association for Cancer Research.

  11. A general regression framework for a secondary outcome in case-control studies.

    PubMed

    Tchetgen Tchetgen, Eric J

    2014-01-01

    Modern case-control studies typically involve the collection of data on a large number of outcomes, often at considerable logistical and monetary expense. These data are of potentially great value to subsequent researchers, who, although not necessarily concerned with the disease that defined the case series in the original study, may want to use the available information for a regression analysis involving a secondary outcome. Because cases and controls are selected with unequal probability, regression analysis involving a secondary outcome generally must acknowledge the sampling design. In this paper, the author presents a new framework for the analysis of secondary outcomes in case-control studies. The approach is based on a careful re-parameterization of the conditional model for the secondary outcome given the case-control outcome and regression covariates, in terms of (a) the population regression of interest of the secondary outcome given covariates and (b) the population regression of the case-control outcome on covariates. The error distribution for the secondary outcome given covariates and case-control status is otherwise unrestricted. For a continuous outcome, the approach sometimes reduces to extending model (a) by including a residual of (b) as a covariate. However, the framework is general in the sense that models (a) and (b) can take any functional form, and the methodology allows for an identity, log or logit link function for model (a).

  12. Genetic variations in the Dravidian population of South West coast of India: Implications in designing case-control studies.

    PubMed

    D'Cunha, Anitha; Pandit, Lekha; Malli, Chaithra

    2017-06-01

    Indian data have been largely missing from genome-wide databases that provide information on genetic variations in different populations. This hinders association studies for complex disorders in India. This study was aimed to determine whether the complex genetic structure and endogamy among Indians could potentially influence the design of case-control studies for autoimmune disorders in the south Indian population. A total of 12 single nucleotide variations (SNVs) related to genes associated with autoimmune disorders were genotyped in 370 healthy individuals belonging to six different caste groups in southern India. Allele frequencies were estimated; genetic divergence and phylogenetic relationship within the various caste groups and other HapMap populations were ascertained. Allele frequencies for all genotyped SNVs did not vary significantly among the different groups studied. Wright's FSTwas 0.001 per cent among study population and 0.38 per cent when compared with Gujarati in Houston (GIH) population on HapMap data. The analysis of molecular variance results showed a 97 per cent variation attributable to differences within the study population and <1 per cent variation due to differences between castes. Phylogenetic analysis showed a separation of Dravidian population from other HapMap populations and particularly from GIH population. Despite the complex genetic origins of the Indian population, our study indicated a low level of genetic differentiation among Dravidian language-speaking people of south India. Case-control studies of association among Dravidians of south India may not require stratification based on language and caste.

  13. Association between bullous pemphigoid and neurologic diseases: a case-control study.

    PubMed

    Casas-de-la-Asunción, E; Ruano-Ruiz, J; Rodríguez-Martín, A M; Vélez García-Nieto, A; Moreno-Giménez, J C

    2014-11-01

    In the past 10 years, bullous pemphigoid has been associated with other comorbidities and neurologic and psychiatric conditions in particular. Case series, small case-control studies, and large population-based studies in different Asian populations, mainland Europe, and the United Kingdom have confirmed this association. However, no data are available for the Spanish population. This was an observational, retrospective, case-control study with 1:2 matching. Fifty-four patients with bullous pemphigoid were selected. We compared the percentage of patients in each group with concurrent neurologic conditions, ischemic heart disease, diabetes, chronic obstructive pulmonary disease, and solid tumors using univariate logistic regression. An association model was constructed with conditional multiple logistic regression. The case group had a significantly higher percentage of patients with cerebrovascular accident and/or transient ischemic attack (odds ratio [OR], 3.06; 95% CI, 1.19-7.87], dementia (OR, 5.52; 95% CI, 2.19-13.93), and Parkinson disease (OR, 5; 95% CI, 1.57-15.94). A significantly higher percentage of cases had neurologic conditions (OR, 6.34; 95% CI, 2.89-13.91). Dementia and Parkinson disease were independently associated with bullous pemphigoid in the multivariate analysis. Patients with bullous pemphigoid have a higher frequency of neurologic conditions. Copyright © 2013 Elsevier España, S.L.U. and AEDV. All rights reserved.

  14. Outlining a Population “at Risk” of Parkinson's Disease: Evidence from a Case-Control Study

    PubMed Central

    Schirinzi, Tommaso; Martella, Giuseppina; D'Elia, Alessio; Di Lazzaro, Giulia; Imbriani, Paola; Madeo, Graziella; Monaco, Leonardo; Maltese, Marta

    2016-01-01

    The multifactorial pathogenesis of Parkinson's Disease (PD) requires a careful identification of populations “at risk” of developing the disease. In this case-control study we analyzed a large Italian population, in an attempt to outline general criteria to define a population “at risk” of PD. We enrolled 300 PD patients and 300 controls, gender and age matched, from the same urban geographical area. All subjects were interviewed on demographics, family history of PD, occupational and environmental toxicants exposure, smoking status, and alcohol consumption. A sample of 65 patients and 65 controls also underwent serum dosing of iron, copper, mercury, and manganese by means of Inductively Coupled-Plasma-Mass-Spectrometry (ICP-MS). Positive family history, toxicants exposure, non-current-smoker, and alcohol nonconsumer status occurred as significant risk factors in our population. The number of concurring risk factors overlapping in the same subject impressively increased the overall risk. No significant differences were measured in the metal serum levels. Our findings indicate that combination of three to four concurrent PD-risk factors defines a condition “at risk” of PD. A simple stratification, based on these questionnaires, might be of help in identifying subjects suitable for neuroprotective strategies. PMID:27651975

  15. Unprovoked seizures after traumatic brain injury: A population-based case-control study.

    PubMed

    Mahler, Benno; Carlsson, Sofia; Andersson, Tomas; Adelöw, Cecilia; Ahlbom, Anders; Tomson, Torbjörn

    2015-09-01

    To quantify the risk of unprovoked seizures after traumatic brain injury (TBI) METHODS: We used the Stockholm Incidence Registry on Epilepsy to carry out a population-based case-control study, including 1,885 cases with incident unprovoked seizures from September 1, 2000 through August 31, 2008, together with 15,080 matched controls. Information of prior hospitalizations for TBI was obtained through record linkage with the Swedish National Inpatient Registry for the period 1980-2008. Relative risks (RRs) for unprovoked seizures were estimated after various TBI diagnoses, and influences of TBI severity and time since trauma were studied in detail. After hospitalization for mild TBI, the RR was 2.0 (95% confidence interval [CI] 1.5-2.7). The RR was higher after brain contusion (5.9, 95% CI 2.4-15.0) or intracranial hemorrhage (ICH) (4.5, 95% CI 2.2-9.0), whereas a combination of both diagnoses led to a further sevenfold increase in RR (42.6, 95% CI 12.2-148.5). The risk was greatest during the first 6 months after severe TBI (RR 48.9, 95% CI 10.9-218.9) or mild TBI (RR 8.1, 95% CI 3.1-21.7), but was still elevated >10 years after any TBI. Herein we present a large population-based case-control study on TBI as a risk factor for unprovoked epileptic seizures, including cases of all ages with individually validated seizure diagnoses. The risk for epileptic seizures was substantially increased after TBI, especially during the first 6 months after the injury and in patients with a combination of ICH and brain contusion. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  16. Fetal Growth and Childhood Cancer: A Population-Based Study

    PubMed Central

    Sørensen, Henrik Toft; Grotmol, Tom; Engeland, Anders; Stephansson, Olof; Gissler, Mika; Tretli, Steinar; Troisi, Rebecca

    2013-01-01

    OBJECTIVE: The etiology of childhood cancers is largely unknown. Studies have suggested that birth characteristics may be associated with risk. Our goal was to evaluate the risk of childhood cancers in relation to fetal growth. METHODS: We conducted a case-control study nested within Nordic birth registries. The study included cancer cases diagnosed in Denmark, Finland, Norway, and Sweden among children born from 1967 to 2010 and up to 10 matched controls per case, totaling 17 698 cases and 172 422 controls. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were derived from conditional logistic regression. RESULTS: Risks of all childhood cancers increased with increasing birth weight (Ptrend ≤ .001). Risks of acute lymphoid leukemia and Wilms tumor were elevated when birth weight was >4000 g and of central nervous system tumors when birth weight was >4500 g. Newborns large for gestational age were at increased risk of Wilms tumor (OR: 2.1 [95% CI: 1.2–3.6]) and connective/soft tissue tumors (OR: 2.1 [95% CI: 1.1–4.4]). In contrast, the risk of acute myeloid leukemia was increased among children born small for gestational age (OR: 1.8 [95% CI: 1.1–3.1]). Children diagnosed with central nervous system tumors at <1 year of age had elevated risk with increasing head circumference (Ptrend < .001). Those with head circumference >39 cm had the highest risk (OR: 4.7 [95% CI: 2.5–8.7]). CONCLUSIONS: In this large, Nordic population-based study, increased risks for several childhood tumors were associated with measures of fetal growth, supporting the hypothesis that tumorigenesis manifesting in childhood is initiated in utero. PMID:24167169

  17. The Distillation of "VISCI": Towards a Better Identification of Suicidal Inmates

    ERIC Educational Resources Information Center

    Frottier, Patrick; Koenig, Franz; Seyringer, Michaela; Matschnig, Teresa; Fruehwald, Stefan

    2009-01-01

    The "Viennese Instrument for Suicidality in Correctional Institutions" (VISCI) presented here is based on the results of a large case-control study and on research on literature examining suicide prevention in general and in the prison population in particular. The aim of this study was to validate the properties of the VISCI to differentiate…

  18. Self-reported Ethnicity, Genetic Structure and the Impact of Population Stratification in a Multiethnic Study

    PubMed Central

    Wang, Hansong; Haiman, Christopher A.; Kolonel, Laurence N.; Henderson, Brian E.; Wilkens, Lynne R.; Le Marchand, Loïc; Stram, Daniel O.

    2011-01-01

    It is well-known that population substructure may lead to confounding in case-control association studies. Here, we examined genetic structure in a large racially and ethnically diverse sample consisting of 5 ethnic groups of the Multiethnic Cohort study (African Americans, Japanese Americans, Latinos, European Americans and Native Hawaiians) using 2,509 SNPs distributed across the genome. Principal component analysis on 6,213 study participants, 18 Native Americans and 11 HapMap III populations revealed 4 important principal components (PCs): the first two separated Asians, Europeans and Africans, and the third and fourth corresponded to Native American and Native Hawaiian (Polynesian) ancestry, respectively. Individual ethnic composition derived from self-reported parental information matched well to genetic ancestry for Japanese and European Americans. STRUCTURE-estimated individual ancestral proportions for African Americans and Latinos are consistent with previous reports. We quantified the East Asian (mean 27%), European (mean 27%) and Polynesian (mean 46%) ancestral proportions for the first time, to our knowledge, for Native Hawaiians. Simulations based on realistic settings of case-control studies nested in the Multiethnic Cohort found that the effect of population stratification was modest and readily corrected by adjusting for race/ethnicity or by adjusting for top PCs derived from all SNPs or from ancestry informative markers; the power of these approaches was similar when averaged across causal variants simulated based on allele frequencies of the 2,509 genotyped markers. The bias may be large in case-only analysis of gene by gene interactions but it can be corrected by top PCs derived from all SNPs. PMID:20499252

  19. Childhood Adversities Increase the Risk of Psychosis: A Meta-analysis of Patient-Control, Prospective- and Cross-sectional Cohort Studies

    PubMed Central

    Varese, Filippo; Smeets, Feikje; Drukker, Marjan; Lieverse, Ritsaert; Lataster, Tineke; Viechtbauer, Wolfgang; Read, John; van Os, Jim; Bentall, Richard P.

    2012-01-01

    Evidence suggests that adverse experiences in childhood are associated with psychosis. To examine the association between childhood adversity and trauma (sexual abuse, physical abuse, emotional/psychological abuse, neglect, parental death, and bullying) and psychosis outcome, MEDLINE, EMBASE, PsychINFO, and Web of Science were searched from January 1980 through November 2011. We included prospective cohort studies, large-scale cross-sectional studies investigating the association between childhood adversity and psychotic symptoms or illness, case-control studies comparing the prevalence of adverse events between psychotic patients and controls using dichotomous or continuous measures, and case-control studies comparing the prevalence of psychotic symptoms between exposed and nonexposed subjects using dichotomous or continuous measures of adversity and psychosis. The analysis included 18 case-control studies (n = 2048 psychotic patients and 1856 nonpsychiatric controls), 10 prospective and quasi-prospective studies (n = 41 803) and 8 population-based cross-sectional studies (n = 35 546). There were significant associations between adversity and psychosis across all research designs, with an overall effect of OR = 2.78 (95% CI = 2.34–3.31). The integration of the case-control studies indicated that patients with psychosis were 2.72 times more likely to have been exposed to childhood adversity than controls (95% CI = 1.90–3.88). The association between childhood adversity and psychosis was also significant in population-based cross-sectional studies (OR = 2.99 [95% CI = 2.12–4.20]) as well as in prospective and quasi-prospective studies (OR = 2.75 [95% CI = 2.17–3.47]). The estimated population attributable risk was 33% (16%–47%). These findings indicate that childhood adversity is strongly associated with increased risk for psychosis. PMID:22461484

  20. Spatial variation in mortality risk for haematological malignancies near a petrochemical refinery: a population-based case-control study

    PubMed Central

    Di Salvo, Francesca; Meneghini, Elisabetta; Vieira, Veronica; Baili, Paolo; Mariottini, Mauro; Baldini, Marco; Micheli, Andrea; Sant, Milena

    2015-01-01

    Introduction The study investigated the geographic variation of mortality risk for hematological malignancies (HMs) in order to identify potential high-risk areas near an Italian petrochemical refinery. Material and methods A population-based case-control study was conducted and residential histories for 171 cases and 338 sex- and age-matched controls were collected. Confounding factors were obtained from interviews with consenting relatives for 109 HM deaths and 267 controls. To produce risk mortality maps, two different approaches were applied. We mapped (1) adptive kernel density relative risk estimation (KDE) for case-control studies which estimates a spatial relative risk function using the ratio between cases and controls’ densities, and (2) estimated odds ratios for case-control study data using generalized additive models (GAMs) to smooth the effect of location, a proxy for exposure, while adjusting for confounding variables. Results No high-risk areas for HM mortality were identified among all subjects (men and women combined), by applying both approaches. Using the adaptive KDE approach, we found a significant increase in death risk only among women in a large area 2–6 km southeast of the refinery and the application of GAMs also identified a similarly-located significant high-risk area among women only (global p-value<0.025). Potential confounding risk factors we considered in the GAM did not alter the results. Conclusion Both approaches identified a high-risk area close to the refinery among women only. Those spatial methods are useful tools for public policy management to determine priority areas for intervention. Our findings suggest several directions for further research in order to identify other potential environmental exposures that may be assessed in forthcoming studies based on detailed exposure modeling. PMID:26073202

  1. Personality as a risk factor in large bowel cancer: data from the Melbourne Colorectal Cancer Study.

    PubMed

    Kune, G A; Kune, S; Watson, L F; Bahnson, C B

    1991-02-01

    In a case control study which formed one arm of a large, population-based investigation of colorectal cancer incidence, aetiology and survival. 'The Melbourne Colorectal Cancer Study', among others, 22 psychosocially orientated questions were asked by personal interview of 637 histologically confirmed new cases of colorectal cancer and 714 age/sex frequency matched community controls, from Melbourne (population 2.81 million). Self-reported childhood or adult life 'unhappiness' was statistically significantly more common among the cancer cases, while 'unhappiness with retirement' was similarly distributed among cases and controls. Questions which were formulated to test a particular personality profile as a cancer risk, and which included the elements of denial and repression of anger and of other negative emotions, a commitment to prevailing social norms resulting in the external appearance of a 'nice' or 'good' person, a suppression of reactions which may offend others and the avoidance of conflict, showed a statistically significant discrimination between cases and controls. The risk of colorectal cancer with respect to this model was independent of the previously found risk factors of diet, beer intake, and family history of colorectal cancer, and was also independent of other potential confounding factors of socioeconomic level, marital status, religion and country of birth. Although the results must be interpreted with caution, the data are consistent with the hypothesis that this personality type may play a role in the clinical expression of colorectal cancer and merits further study.

  2. Characteristics of boys with the so-called true undescended testis diagnosed at the third postnatal month--a population-based case-control study.

    PubMed

    Mavrogenis, Stelios; Urbán, Robert; Czeizel, Andrew E

    2015-07-01

    Undescended testis (cryptorchidism) is a common congenital abnormality of male genital organs diagnosed at birth followed with frequent postnatal descensus. However, the so-called isolated true undescended testis (ITUT) diagnosed at the third postnatal month seems to be an independent defect-entity, and this hypothesis was planned to confirm or reject in the study. The evaluation of birth outcomes and maternal socio-demographic data of cases with ITUT in the population-based large dataset of the Hungarian Congenital Abnormality Registry. There was a higher rate of preterm birth and particularly of low birthweight in 2052 cases with ITUT compared to 24,814 population male controls without any defects. The rate of twins was not higher in cases with older mothers, higher birth order and lower socio-economic status. The comparison of data of boys with undescended testis diagnosed at birth found in the previous study and with ITUT in this study confirmed our hypothesis. Undescended testis can be differentiated into two subgroups: boys with frequent postnatal descensus mainly after preterm delivery and boys with ITUT without postnatal testis descensus with frequent intrauterine growth restriction, older mothers with higher birth order and low socio-economic status.

  3. Association of TRPV4 gene polymorphisms with chronic obstructive pulmonary disease.

    PubMed

    Zhu, Guohua; Gulsvik, Amund; Bakke, Per; Ghatta, Srinivas; Anderson, Wayne; Lomas, David A; Silverman, Edwin K; Pillai, Sreekumar G

    2009-06-01

    Chronic obstructive pulmonary disease (COPD) is characterized by airway epithelial damage, bronchoconstriction, parenchymal destruction and mucus hypersecretion. Upon activation by a broad range of stimuli, transient receptor potential vanilloid 4 (TRPV4) functions to control airway epithelial cell volume and epithelial and endothelial permeability; it also triggers bronchial smooth muscle contraction and participates in autoregulation of mucociliary transport. These functions of TRPV4 may be important for the regulation of COPD pathogenesis, so TRPV4 is a candidate gene for COPD. We genotyped 20 single nucleotide polymorphisms (SNPs) in TRPV4, and tested qualitative COPD and quantitative FEV(1) and FEV(1)/(F)VC phenotypes in two independent large populations. The family population had 606 pedigrees including 1891 individuals, and the case-control sample included 953 COPD cases and 956 controls. Family-based association tests were performed in the family data. Logistic regression and linear models were used in the case-control data to replicate the association results. In the family data, seven out of 20 SNPs tested were associated with COPD (2.5 x 10(-4) < or = P < or = 0.04) and six SNPs were associated with FEV(1)/VC (0.02 < or = P < or = 0.03) from family-based association tests (PBAT) analysis. Four out of the seven SNPs associated with COPD demonstrated replicated associations with the same effect directions in the case-control population (0.02 < or = P < or = 0.03). Significant haplotype associations supported the results of single SNP analyses. Thus, polymorphisms in the TRPV4 gene are associated with COPD.

  4. The National Birth Defects Prevention Study: a review of the methods

    PubMed Central

    Reefhuis, Jennita; Gilboa, Suzanne M.; Anderka, Marlene; Browne, Marilyn L.; Feldkamp, Marcia L.; Hobbs, Charlotte A.; Jenkins, Mary M.; Langlois, Peter H.; Newsome, Kimberly B.; Olshan, Andrew F.; Romitti, Paul A.; Shapira, Stuart K.; Shaw, Gary M.; Tinker, Sarah C.; Honein, Margaret A.

    2015-01-01

    Background The National Birth Defects Prevention Study (NBDPS) is a large population-based multi-center case-control study of major birth defects in the United States. Methods Data collection took place from 1998 through 2013 on pregnancies ending between October 1997 and December 2011. Cases could be live born, stillborn or induced terminations, and were identified from birth defects surveillance programs in Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas and Utah. Controls were live born infants without major birth defects identified from the same geographical regions and time periods as cases via either vital records or birth hospitals. Computer-assisted telephone interviews were completed with women between 6 weeks and 24 months after the estimated date of delivery. After completion of interviews, families received buccal cell collection kits for the mother, father and infant (if living). Results There were 47,832 eligible cases and 18,272 eligible controls. Among these, 32,187 (67%) and 11,814 (65%) respectively, provided interview information about their pregnancies. Buccal cell collection kits with a cytobrush for at least one family member were returned by 19,065 case and 6,211 control families (65% and 59% of those who were sent a kit). More than 500 projects have been proposed by the collaborators and over 200 manuscripts published using data from the NBDPS through December 2014. Conclusion The NBDPS has made substantial contributions to the field of birth defects epidemiology through its rigorous design, including case classification, detailed questionnaire and specimen collection, large study population, and collaborative activities across Centers. PMID:26033852

  5. The National Birth Defects Prevention Study: A review of the methods.

    PubMed

    Reefhuis, Jennita; Gilboa, Suzanne M; Anderka, Marlene; Browne, Marilyn L; Feldkamp, Marcia L; Hobbs, Charlotte A; Jenkins, Mary M; Langlois, Peter H; Newsome, Kimberly B; Olshan, Andrew F; Romitti, Paul A; Shapira, Stuart K; Shaw, Gary M; Tinker, Sarah C; Honein, Margaret A

    2015-08-01

    The National Birth Defects Prevention Study (NBDPS) is a large population-based multicenter case-control study of major birth defects in the United States. Data collection took place from 1998 through 2013 on pregnancies ending between October 1997 and December 2011. Cases could be live born, stillborn, or induced terminations, and were identified from birth defects surveillance programs in Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, and Utah. Controls were live born infants without major birth defects identified from the same geographical regions and time periods as cases by means of either vital records or birth hospitals. Computer-assisted telephone interviews were completed with women between 6 weeks and 24 months after the estimated date of delivery. After completion of interviews, families received buccal cell collection kits for the mother, father, and infant (if living). There were 47,832 eligible cases and 18,272 eligible controls. Among these, 32,187 (67%) and 11,814 (65%), respectively, provided interview information about their pregnancies. Buccal cell collection kits with a cytobrush for at least one family member were returned by 19,065 case and 6,211 control families (65% and 59% of those who were sent a kit). More than 500 projects have been proposed by the collaborators and over 200 manuscripts published using data from the NBDPS through December 2014. The NBDPS has made substantial contributions to the field of birth defects epidemiology through its rigorous design, including case classification, detailed questionnaire and specimen collection, large study population, and collaborative activities across Centers. © 2015 Wiley Periodicals, Inc.

  6. Calcified Neurocysticercosis Associates with Hippocampal Atrophy: A Population-Based Study

    PubMed Central

    Del Brutto, Oscar H.; Salgado, Perla; Lama, Julio; Del Brutto, Victor J.; Campos, Xavier; Zambrano, Mauricio; García, Héctor H.

    2015-01-01

    Calcified neurocysticercosis has been associated with hippocampal atrophy in patients with refractory epilepsy, but the relevance of this association in the population at large is unknown. We assessed calcified cysticerci and its association with hippocampal atrophy in elderly persons living in Atahualpa, an Ecuadorian village endemic for neurocysticercosis. All Atahualpa residents ≥ 60 years of age were invited to undergo computed tomography/magnetic resonance imaging for neurocysticercosis detection. Twenty-eight (11%) out of 248 enrolled persons had calcified cysticerci (case-patients) and were matched 1:1 by age, sex, and years of education to individuals without neurocysticercosis on computed tomography/magnetic resonance imaging (controls). Four case-patients and none of the controls had epilepsy (P = 0.134). Cognitive performance was similar across both groups. The Scheltens' medial temporal atrophy scale was used for hippocampal rating in case-patients and matched controls without neurocysticercosis. Mean score in the Scheltens' scale was higher in case-patients than in controls (P < 0.001). Atrophic hippocampi were noticed in 19 case-patients and five controls (P = 0.003). Atrophy was bilateral in 11 case-patients and unilateral in eight. All case-patients with unilateral hippocampal atrophy had at least one ipsilateral calcification. This study shows an association between calcified cysticerci and hippocampal atrophy and raises the possibility of an inflammation-mediated hippocampal damage as the responsible mechanism for these findings. PMID:25349375

  7. Birth characteristics and Wilms tumors in children in the Nordic countries: a register-based case-control study.

    PubMed

    Schüz, Joachim; Schmidt, Lisbeth Samsø; Kogner, Per; Lähteenmäki, Päivi M; Pal, Niklas; Stokland, Tore; Schmiegelow, Kjeld

    2011-05-01

    Little is known about causes of Wilms tumor. Because of the young age at diagnosis, several studies have looked at various birth characteristics. We conducted a registry-based case-control study involving 690 cases of Wilms tumor aged 0-14 years, occurring in Denmark, Finland, Norway or Sweden during 1985-2006, individually matched to five controls drawn randomly from the Nordic childhood population. Information on birth characteristics was obtained from the population-based medical birth registries. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis. We observed a distinct association between Wilms tumor and high birth weight (≥4 kg) for girls (OR 1.97, CI 1.50-2.59) but not for boys (1.04, 0.78-1.38); overall, the OR was 1.43 (1.17-1.74). Among girls, risk increased by 28% (15-42%) per 500 g increase in birth weight. Large-for-gestational age girls also had a higher risk (2.48, 1.51-4.05), whereas no effect was seen for boys (1.12, 0.60-2.07). An association was seen with Apgar score at 5 min < 7 for both sexes combined (5.13, 2.55-10.3). ORs close to unity were seen for parental age and birth order. In our large-scale, registry-based study, we confirmed earlier observations of an association between high birth weight and risk of Wilms tumor, but we found an effect only in girls. The higher risk of infants with low Apgar score might reflect hypoxia causing cell damage, adverse side effects of neonatal treatment or reverse causation as low Apgar score might indicate the presence of a tumor. Copyright © 2010 UICC.

  8. Association of Phosphodiesterase 4D with ischemic stroke: a population-based case-control study.

    PubMed

    Woo, Daniel; Kaushal, Ritesh; Kissela, Brett; Sekar, Padmini; Wolujewicz, Michael; Pal, Prodipto; Alwell, Kathleen; Haverbusch, Mary; Ewing, Irene; Miller, Rosie; Kleindorfer, Dawn; Flaherty, Matthew; Chakraborty, Ranajit; Deka, Ranjan; Broderick, Joseph

    2006-02-01

    The Phosphodiesterase 4D (PDE4D) gene was reported recently to be associated with ischemic stroke in an Icelandic population. The association was found predominately with large vessel and cardioembolic stroke. However, 2 recent reports were unable to confirm this association, although a trend toward association with cardioembolic stroke was reported. None of the reports included significant proportions of blacks. We tested for genotype and haplotype association of polymorphisms of the PDE4D gene with ischemic stroke in a population-based, biracial, case-control study. A total of 357 cases of ischemic stroke and 482 stroke-free controls from the same community were examined. Single nucleotide polymorphisms (SNPs) were chosen based on significant associations reported previously. Linkage disequilibrium (LD), SNP, and haplotype association analysis was performed using PHASE 2.0 and Haploview 3.2. Although several univariate associations were identified, only 1 SNP (rs2910829) was found to be significantly associated with cardioembolic stroke among both whites and blacks. The rs152312 SNP was associated with cardioembolic stroke among whites after multiple comparison corrections. The same SNP was not associated with cardioembolic stroke among blacks. However, significant haplotype association was identified for both whites and blacks for all ischemic stroke, cardioembolic stroke, and stroke of unknown origin. Haplotype association was identified for small vessel stroke among whites. PDE4D is a risk factor for ischemic stroke and, in particular, for cardioembolic stroke, among whites and blacks. Further study of this gene is warranted.

  9. Household demographic determinants of Ebola epidemic risk.

    PubMed

    Adams, Ben

    2016-03-07

    A salient characteristic of Ebola, and some other infectious diseases such as Tuberculosis, is intense transmission among small groups of cohabitants and relatively limited indiscriminate transmission in the wider population. Here we consider a mathematical model for an Ebola epidemic in a population structured into households of equal size. We show that household size, a fundamental demographic unit, is a critical factor that determines the vulnerability of a community to epidemics, and the effort required to control them. Our analysis is based on the household reproduction number, but we also consider the basic reproduction number, intrinsic growth rate and final epidemic size. We show that, when other epidemiological parameters are kept the same, all of these quantifications of epidemic growth and size are increased by larger households and more intense within-household transmission. We go on to model epidemic control by case detection and isolation followed by household quarantine. We show that, if household quarantine is ineffective, the critical probability with which cases must be detected to halt an epidemic increases significantly with each increment in household size and may be a very challenging target for communities composed of large households. Effective quarantine may, however, mitigate the detrimental impact of large household sizes. We conclude that communities composed of large households are fundamentally more vulnerable to epidemics of infectious diseases primarily transmitted by close contact, and any assessment of control strategies for these epidemics should take into account the demographic structure of the population. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Organochlorine Pesticides and Risk of Endometriosis: Findings from a Population-Based Case–Control Study

    PubMed Central

    De Roos, Anneclaire J.; Thompson, Mary Lou; Sathyanarayana, Sheela; Scholes, Delia; Barr, Dana Boyd; Holt, Victoria L.

    2013-01-01

    Background: Endometriosis is considered an estrogen-dependent disease. Persistent environmental chemicals that exhibit hormonal properties, such as organochlorine pesticides (OCPs), may affect endometriosis risk. Objective: We investigated endometriosis risk in relation to environmental exposure to OCPs. Methods: We conducted the present analyses using data from the Women’s Risk of Endometriosis (WREN) study, a population-based case–control study of endometriosis conducted among 18- to 49-year-old female enrollees of a large health care system in western Washington State. OCP concentrations were measured in sera from surgically confirmed endometriosis cases (n = 248) first diagnosed between 1996 and 2001 and from population-based controls (n = 538). We estimated odds ratios (OR) and 95% CIs using unconditional logistic regression, adjusting for age, reference date year, serum lipids, education, race/ethnicity, smoking, and alcohol intake. Results: Our data suggested increased endometriosis risk associated with serum concentrations of β-hexachlorocyclohexane (HCH) (third vs. lowest quartile: OR = 1.7; 95% CI: 1.0, 2.8; highest vs. lowest quartile OR = 1.3; 95% CI: 0.8, 2.4) and mirex (highest vs. lowest category: OR = 1.5; 95% CI: 1.0, 2.2). The association between serum β-HCH concentrations and endometriosis was stronger in analyses restricting cases to those with ovarian endometriosis (third vs. lowest quartile: OR = 2.5; 95% CI: 1.5, 5.2; highest vs. lowest quartile: OR = 2.5; 95% CI: 1.1, 5.3). Conclusions: In our case–control study of women enrolled in a large health care system in the U.S. Pacific Northwest, serum concentrations of β-HCH and mirex were positively associated with endometriosis. Extensive past use of environmentally persistent OCPs in the United States or present use in other countries may affect the health of reproductive-age women. Citation: Upson K, De Roos AJ, Thompson ML, Sathyanarayana S, Scholes D, Barr DB, Holt VL. 2013. Organochlorine pesticides and risk of endometriosis: findings from a population-based case–control study. Environ Health Perspect 121:1319–1324; http://dx.doi.org/10.1289/ehp.1306648 PMID:24192044

  11. Case-spouse control design in practice: an experience in estimating smoking and chronic obstructive pulmonary disease deaths in Chinese adults.

    PubMed

    Jiang, Jingmei; Liu, Boqi; Sitas, Freddy; Zeng, Xianjia; Chen, Junshi; Han, Wei; Zou, Xiaonong; Wu, Yanping; Zhao, Ping; Li, Junyao

    2010-05-01

    We assessed the effect of smoking on death from chronic obstructive pulmonary disease (COPD) in China by employing a large population-based, case-spouse control study design using data from a nationwide survey of mortality. During 1989-1991, a nationwide retrospective survey of mortality was conducted in China. For approximately 1,000,000 adults dying from all causes during 1986-1988, their surviving spouses or other informants provided detailed information about their own as well as the deceased person's smoking history. For this study, 183,393 individuals who died of COPD at age > or = 40 years were taken as cases, while 272,984 sex-matched surviving spouses of subjects who died from any cause were taken as controls. COPD death rates for smokers were more than twice as high as those of non-smokers, with a dose-response risk pattern, despite the fact that COPD death rates varied widely by region and age. Tobacco accounted for 41.4% of COPD deaths in men, but only 13.5% of those in women, who had a lower rate of smoking. A case-spouse control study, as an alternative design, is valid and feasible in utilizing information from population-based, retrospective mortality survey data for an analytical epidemiological study of disease etiology. Copyright 2010 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.

  12. Japanese population structure, based on SNP genotypes from 7003 individuals compared to other ethnic groups: effects on population-based association studies.

    PubMed

    Yamaguchi-Kabata, Yumi; Nakazono, Kazuyuki; Takahashi, Atsushi; Saito, Susumu; Hosono, Naoya; Kubo, Michiaki; Nakamura, Yusuke; Kamatani, Naoyuki

    2008-10-01

    Because population stratification can cause spurious associations in case-control studies, understanding the population structure is important. Here, we examined Japanese population structure by "Eigenanalysis," using the genotypes for 140,387 SNPs in 7003 Japanese individuals, along with 60 European, 60 African, and 90 East-Asian individuals, in the HapMap project. Most Japanese individuals fell into two main clusters, Hondo and Ryukyu; the Hondo cluster includes most of the individuals from the main islands in Japan, and the Ryukyu cluster includes most of the individuals from Okinawa. The SNPs with the greatest frequency differences between the Hondo and Ryukyu clusters were found in the HLA region in chromosome 6. The nonsynonymous SNPs with the greatest frequency differences between the Hondo and Ryukyu clusters were the Val/Ala polymorphism (rs3827760) in the EDAR gene, associated with hair thickness, and the Gly/Ala polymorphism (rs17822931) in the ABCC11 gene, associated with ear-wax type. Genetic differentiation was observed, even among different regions in Honshu Island, the largest island of Japan. Simulation studies showed that the inclusion of different proportions of individuals from different regions of Japan in case and control groups can lead to an inflated rate of false-positive results when the sample sizes are large.

  13. Lifelong vegetarianism and breast cancer risk: a large multicentre case control study in India.

    PubMed

    Gathani, Toral; Barnes, Isobel; Ali, Raghib; Arumugham, Rajkumar; Chacko, Raju; Digumarti, Raghunadharao; Jivarajani, Parimal; Kannan, Ravi; Loknatha, Dasappa; Malhotra, Hemant; Mathew, Beela S

    2017-01-18

    The lower incidence of breast cancer in Asian populations where the intake of animal products is lower than that of Western populations has led some to suggest that a vegetarian diet might reduce breast cancer risk. Between 2011 and 2014 we conducted a multicentre hospital based case-control study in eight cancer centres in India. Eligible cases were women aged 30-70 years, with newly diagnosed invasive breast cancer (ICD10 C50). Controls were frequency matched to the cases by age and region of residence and chosen from the accompanying attendants of the patients with cancer or those patients in the general hospital without cancer. Information about dietary, lifestyle, reproductive and socio-demographic factors were collected using an interviewer administered structured questionnaire. Multivariate logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals for the risk of breast cancer in relation to lifelong vegetarianism, adjusting for known risk factors for the disease. The study included 2101 cases and 2255 controls. The mean age at recruitment was similar in cases (49.7 years (SE 9.7)) and controls (49.8 years (SE 9.1)). About a quarter of the population were lifelong vegetarians and the rates varied significantly by region. On multivariate analysis, with adjustment for known risk factors for the disease, the risk of breast cancer was not decreased in lifelong vegetarians (OR 1.09 (95% CI 0.93-1.29)). Lifelong exposure to a vegetarian diet appears to have little, if any effect on the risk of breast cancer.

  14. Selection bias in population-based cancer case-control studies due to incomplete sampling frame coverage.

    PubMed

    Walsh, Matthew C; Trentham-Dietz, Amy; Gangnon, Ronald E; Nieto, F Javier; Newcomb, Polly A; Palta, Mari

    2012-06-01

    Increasing numbers of individuals are choosing to opt out of population-based sampling frames due to privacy concerns. This is especially a problem in the selection of controls for case-control studies, as the cases often arise from relatively complete population-based registries, whereas control selection requires a sampling frame. If opt out is also related to risk factors, bias can arise. We linked breast cancer cases who reported having a valid driver's license from the 2004-2008 Wisconsin women's health study (N = 2,988) with a master list of licensed drivers from the Wisconsin Department of Transportation (WDOT). This master list excludes Wisconsin drivers that requested their information not be sold by the state. Multivariate-adjusted selection probability ratios (SPR) were calculated to estimate potential bias when using this driver's license sampling frame to select controls. A total of 962 cases (32%) had opted out of the WDOT sampling frame. Cases age <40 (SPR = 0.90), income either unreported (SPR = 0.89) or greater than $50,000 (SPR = 0.94), lower parity (SPR = 0.96 per one-child decrease), and hormone use (SPR = 0.93) were significantly less likely to be covered by the WDOT sampling frame (α = 0.05 level). Our results indicate the potential for selection bias due to differential opt out between various demographic and behavioral subgroups of controls. As selection bias may differ by exposure and study base, the assessment of potential bias needs to be ongoing. SPRs can be used to predict the direction of bias when cases and controls stem from different sampling frames in population-based case-control studies.

  15. Identification of target risk groups for population-based Clostridium difficile infection prevention strategies using a population attributable risk approach.

    PubMed

    Oh, Sung-Hee; Kang, Hye-Young

    2018-01-01

    We aimed to determine risk factors associated with Clostridium difficile infection (CDI) and assess the contributions of these factors on CDI burden. We conducted a 1:4 matched case-control study using a national claims dataset. Cases were incident CDI without a history of CDI in the previous 84 days, and were age- and sex-matched with control patients. We ascertained exposure, defined as a history of morbidities and drug use within 90 days. The population attributable risk (PAR) percent for risk factors was estimated using odds ratios (ORs) obtained from the case-control study. Overall, the strongest CDI-associated risk factors, which have significant contributions to the CDI burden as well, were the experience of gastroenteritis (OR=5.08, PAR%=17.09%) and use of antibiotics (OR=1.69, PAR%=19.00%), followed by the experiences of female pelvic infection, irritable bowel syndrome, inflammatory bowel disease, and pneumonia, and use of proton-pump inhibitors (OR=1.52-2.37, PAR%=1.95-2.90). The control of risk factors that had strong association with CDI and affected large proportions of total CDI cases would be beneficial for CDI prevention. We suggest performing CDI testing for symptomatic patients with gastroenteritis and implementing antibiotics stewardship. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  16. Statins and hip fracture risk in men: a population-based case-control study.

    PubMed

    Adams, Annette L; Shi, Jiaxiao M; Reynolds, Kristi; Haque, Reina; Cheetham, T Craig; Kawatkar, Aniket A; Fithian, Donald C; Jacobsen, Steven J

    2015-11-01

    To estimate the association between hydroxymethylglutaryl-CoA inhibitor (statin) use and hip fracture. We conducted a population-based case-control study. Cases were 6774 male enrollees in a large managed care organization, aged 45 or more years, with an incident hip fracture from 1997 to 2006. Controls without fracture (n = 6774) were matched to cases on age, race, and medical center. Electronic information on pharmaceutical use was used to identify the dispensing of statins from 1991 forward. Overall, 1884 (27.8%) cases and 2150 controls (31.7%) used a statin before index date (matched odds ratio [mOR] = 0.81, 95% confidence interval [CI] = 0.74-0.87). Adjustment for comorbidity burden strengthened the magnitude of the overall association (mOR = 0.68, CI = 0.62-0.74). The adjusted association was similar across age groups but was strongest among men aged 80 years or more (mOR = 0.62, CI = 0.54-0.71) and was most pronounced in African Americans (mOR = 0.43, CI = 0.28-0.64). Greater duration of statin use did not alter the odds ratios. These data add to the growing evidence of a potential protective effect of statin use on bone health. However, these results need to be replicated in a prospective study that can account for confounding by indication which may explain these findings. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Mammary tumor associated Hspb1 mutation and screening of eight cat populations of the world.

    PubMed

    Saif, R; Awan, A R; Lyons, L; Gandolfi, B; Tayyab, M; Ellahi Babar, M; Wasim, M

    2016-01-01

    Current research highlights the Hspb1 based screening of eight cat populations of the world to investigate the association of newly found locus within cat mammary tumors. Total 180 cats were screened on the basis of Hspb1 4 bp deletion locus (1514-1517del4) which was observed in six mammary tumor cases in Siamese cat breed. Case-control association study revealed the non-significance with P=0.201 and an overall mutant allele frequency of 0.30 ranging from 0.20-0.40 was observed in other cat populations. Similarly, HWE was also obeyed in combined population samples with P=0.860 and found non-significant with range of 0.429-0.708 in other non-Pakistani cat populations as well. These results might be helpful to understand the association of this novel locus in a better way with large sample size of cases and may also serve as a potential marker for mammary tumor diagnosis, particularly in cats and generally in all other animal populations in comparative genetics and genomics context.

  18. Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

    PubMed

    Rucker, James J H; Tansey, Katherine E; Rivera, Margarita; Pinto, Dalila; Cohen-Woods, Sarah; Uher, Rudolf; Aitchison, Katherine J; Craddock, Nick; Owen, Michael J; Jones, Lisa; Jones, Ian; Korszun, Ania; Barnes, Michael R; Preisig, Martin; Mors, Ole; Maier, Wolfgang; Rice, John; Rietschel, Marcella; Holsboer, Florian; Farmer, Anne E; Craig, Ian W; Scherer, Stephen W; McGuffin, Peter; Breen, Gerome

    2016-02-15

    Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD. In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset. We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p = .0002). After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. On estimation of time-dependent attributable fraction from population-based case-control studies.

    PubMed

    Zhao, Wei; Chen, Ying Qing; Hsu, Li

    2017-09-01

    Population attributable fraction (PAF) is widely used to quantify the disease burden associated with a modifiable exposure in a population. It has been extended to a time-varying measure that provides additional information on when and how the exposure's impact varies over time for cohort studies. However, there is no estimation procedure for PAF using data that are collected from population-based case-control studies, which, because of time and cost efficiency, are commonly used for studying genetic and environmental risk factors of disease incidences. In this article, we show that time-varying PAF is identifiable from a case-control study and develop a novel estimator of PAF. Our estimator combines odds ratio estimates from logistic regression models and density estimates of the risk factor distribution conditional on failure times in cases from a kernel smoother. The proposed estimator is shown to be consistent and asymptotically normal with asymptotic variance that can be estimated empirically from the data. Simulation studies demonstrate that the proposed estimator performs well in finite sample sizes. Finally, the method is illustrated by a population-based case-control study of colorectal cancer. © 2017, The International Biometric Society.

  20. Local bladder cancer clusters in southeastern Michigan accounting for risk factors, covariates and residential mobility.

    PubMed

    Jacquez, Geoffrey M; Shi, Chen; Meliker, Jaymie R

    2015-01-01

    In case control studies disease risk not explained by the significant risk factors is the unexplained risk. Considering unexplained risk for specific populations, places and times can reveal the signature of unidentified risk factors and risk factors not fully accounted for in the case-control study. This potentially can lead to new hypotheses regarding disease causation. Global, local and focused Q-statistics are applied to data from a population-based case-control study of 11 southeast Michigan counties. Analyses were conducted using both year- and age-based measures of time. The analyses were adjusted for arsenic exposure, education, smoking, family history of bladder cancer, occupational exposure to bladder cancer carcinogens, age, gender, and race. Significant global clustering of cases was not found. Such a finding would indicate large-scale clustering of cases relative to controls through time. However, highly significant local clusters were found in Ingham County near Lansing, in Oakland County, and in the City of Jackson, Michigan. The Jackson City cluster was observed in working-ages and is thus consistent with occupational causes. The Ingham County cluster persists over time, suggesting a broad-based geographically defined exposure. Focused clusters were found for 20 industrial sites engaged in manufacturing activities associated with known or suspected bladder cancer carcinogens. Set-based tests that adjusted for multiple testing were not significant, although local clusters persisted through time and temporal trends in probability of local tests were observed. Q analyses provide a powerful tool for unpacking unexplained disease risk from case-control studies. This is particularly useful when the effect of risk factors varies spatially, through time, or through both space and time. For bladder cancer in Michigan, the next step is to investigate causal hypotheses that may explain the excess bladder cancer risk localized to areas of Oakland and Ingham counties, and to the City of Jackson.

  1. RELIANCE ON GEOCODED MATERNAL RESIDENCE: IMPACT ON A POPULATION-BASED CASE-CONTROL STUDY OF AIR QUALITY AND BIRTH DEFECTS

    EPA Science Inventory

    Introduction: Unbiased geocoding of maternal residence is critical to the success of an ongoing population-based case-control study of exposure to five criteria air pollutants and the risk of selected birth defects in seven Texas counties between 1997 and 2000. The geocoded res...

  2. Senna treatment in pregnant women and congenital abnormalities in their offspring--a population-based case-control study.

    PubMed

    Acs, Nándor; Bánhidy, Ferenc; Puhó, Erzsébet H; Czeizel, Andrew E

    2009-07-01

    Previously, the possible teratogenic effect of frequently used laxative drug, senna has not been checked in case-control epidemiological study. Objective of the study was the comparison of cases with congenital abnormalities (CAs) and their matched controls without CAs in the population-based large data set of the Hungarian Case-Control Surveillance System of Congenital Abnormalities. Of 22,843 cases with CA, 506 (2.2%) had mothers with senna treatment, while of 38,151 control newborn infants without CA, 937 (2.5%) were born to mothers with senna treatment (adjusted OR with 95% CI: 1.0, 0.9-1.1), and of 834 malformed controls with Down syndrome, 26 (3.1%) had mothers with the use of senna (OR with 95% CI: 0.7, 0.5-1.1). The range of senna doses was between 10mg and 30 mg, but most pregnant women used 20mg daily. The mothers with senna treatment showed the characteristics of pregnant women with constipation (elder with larger proportion of primiparae). There was no higher risk for 23 different CA groups after the senna treatment during the second and/or third gestational month of 260 mothers, i.e. in the critical period of most major CAs, compared with their 500 matched controls. Gestational age at delivery was somewhat longer (0.2 week) and the rate of preterm birth was lower (6.6% vs. 9.2%) in newborn infants without CA born to mothers with senna treatment compared with babies born to mothers without senna treatment. In conclusion, senna treatment did not associate with a higher risk of CAs in the offspring of pregnant women with constipation.

  3. Association of atrial fibrillation and cancer: Analysis from two large population-based case-control studies.

    PubMed

    Saliba, Walid; Rennert, Hedy S; Gronich, Naomi; Gruber, Stephen B; Rennert, Gad

    2018-01-01

    An association between atrial fibrillation (AF) and risk of cancer has been suggested in several studies, including prospective cohort studies. However, the magnitude and the temporal nature of this association remain unclear. Data from two large prospective population-based case-control studies, the Molecular Epidemiology of Colorectal Cancer (MECC, n = 8,383) and the Breast Cancer in Northern Israel Study (BCINIS, n = 11,608), were used to better understand the nature and temporality of a possible association between cancer diagnosis and AF events before and after cancer diagnosis. A case-control study approach was employed to study prior AF as a risk factor for cancer, and a cohort study approach was employed to study incident cancer as a risk factor for AF. AF was associated with a significant reduced odds of cancer as reflected in the case-control approach, with an adjusted OR = 0.77 (95% CI, 0.65-0.91), while cancer was not found to be significantly associated with elevated risk of AF in the cohort approach, with an adjusted HR = 1.10 (0.98-1.23). The immediate period (90 days) after an AF event was associated with a 1.85 times increased risk of cancer, and the immediate period after the diagnosis of cancer was associated with a 3.4 fold increased risk of AF. These findings probably reflect both the effect of acute transient conditions associated with new cancer diagnosis and detection bias. Similar results were identified with colorectal and breast cancer cases. Atrial fibrillation of longer than 90 days duration is associated with reduced odds of new cancer diagnosis. The results of this study suggest that an association observed in prior research may be due to instances related to cancer diagnosis and detection bias rather than a causal relationship. However, there may be bias in the sampling and residual confounding that distort the associations.

  4. Cigarette Smoking and the Risk of Barrett's Esophagus

    PubMed Central

    Kubo, Ai; Levin, T.R.; Block, Gladys; Rumore, Gregory; Quesenberry, Charles P.; Buffler, Patricia; Corley, Douglas A.

    2008-01-01

    Introduction We examined the association between smoking and the risk of Barrett's esophagus (BE), a metaplastic precursor to esophageal adenocarcinoma. Methods We conducted a case-control study within the Kaiser Permanente Northern California population. Patients with a new diagnosis of BE (n=320) were matched to persons with gastroesophageal reflux disease (GERD) (n=316) and to population controls (n=317). Information was collected using validated questionnaires from direct in-person interviews and electronic databases. Analyses used multivariate unconditional logistic regression that controlled for age, gender, race and education. Results Ever smoking status, smoking intensity (pack-years), and smoking cessation were not associated with the risk of BE. Stratified analyses suggested that ever smoking may be associated with an increased risk of BE among some groups (compared to population controls): persons with long-segment Barrett's esophagus (odds ratio [OR]=1.72, 95% confidence interval [CI] 1.12-2.63); subjects without GERD symptoms (OR=3.98, 95% CI 1.58-10.0); obese subjects (OR=3.38, 95%CI 1.46-7.82); and persons with a large abdominal circumference (OR=3.02, 95%CI (1.18-2.75)). Conclusion Smoking was not a strong or consistent risk factor for BE in a large community-based study, although associations may be present in some population subgroups. PMID:18853262

  5. Occupation and malignant lymphoma: a population based case control study in Germany

    PubMed Central

    Mester, B; Nieters, A; Deeg, E; Elsner, G; Becker, N; Seidler, A

    2006-01-01

    Aims To identify occupations suspected to be associated with malignant lymphoma and to generate new hypotheses about occupational risks in a multicentre, population based case control study. Methods Male and female patients with malignant lymphoma (n = 710) aged 18–80 years of age were prospectively recruited in six study regions in Germany. For each newly recruited lymphoma case, a sex, region, and age matched control was drawn from the population registers. Odds ratios and 95% confidence intervals for major occupations and industries were calculated using conditional logistic regression analysis, adjusted for smoking (in pack‐years) and alcohol consumption. Patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression analysis. Results The following economic/industrial sectors were positively associated with lymphoma: food products, beverages, tobacco; paper products, publishing and printing; and metals. Chemicals; real estate, renting, and business activities were negatively associated with lymphoma diagnosis. The authors observed an increased overall lymphoma risk among architects; maids; farmers; glass formers; and construction workers. Shoemaking and leather goods making was negatively associated with the lymphoma diagnosis (although based on small numbers). In the occupational group analysis of lymphoma subentities, Hodgkin's lymphoma was significantly associated only with rubber and plastic products making; diffuse large B cell lymphoma risk was considerably increased among metal processors; follicular lymphoma showed highly significant risk increases for several occupational groups (medical, dental, and veterinary workers; sales workers; machinery fitters; and electrical fitters); and multiple myeloma showed a particularly pronounced risk increase for farmers as well as for agriculture and animal husbandry workers. Conclusions The results partly confirm previously defined occupational risks. Occupational risk factors for follicular lymphomas might differ from the overall risk factors for malignant lymphoma. PMID:16361401

  6. Cardiac glycosides use and the risk of lung cancer: a nested case-control study.

    PubMed

    Couraud, Sébastien; Azoulay, Laurent; Dell'Aniello, Sophie; Suissa, Samy

    2014-08-08

    Two studies have reported statistically significant associations between the use of cardiac glycosides (CGs) and an increased risk of lung cancer. However, these studies had a number of methodological limitations. Thus, the objective of this study was to assess this association in a large population-based cohort of patients. We used the United Kingdom Clinical Practice Research Datalink (CPRD) to identify a cohort of patients, at least 40 years of age, newly-diagnosed with heart failure, or supra-ventricular arrhythmia. A nested case-control analysis was conducted where each incident case of lung cancer identified during follow-up was randomly matched with up to 10 controls. Exposure to CGs was assessed in terms of ever use, cumulative duration of use and cumulative dose. Rate ratios (RRs) with 95% confidence intervals (CIs) were estimated using conditional logistic regression after adjusting for potential confounders. A total of 129,002 patients were included, and followed for a mean (SD) of 4.7 (3.8) years. During follow-up, 1237 patients were newly-diagnosed with lung cancer. Overall, ever use of CGs was not associated with an increased risk of lung cancer when compared to never use (RR = 1.09, 95% CI: 0.94-1.26). In addition, no dose-response relationship was observed in terms of cumulative duration of use and cumulative dose with all RRs around the null value across quartile categories. The results of this large population-based study indicate that the use of CGs is not associated with an increased risk of lung cancer.

  7. Exposure to genocide and risk of suicide in Rwanda: a population-based case-control study.

    PubMed

    Rubanzana, Wilson; Hedt-Gauthier, Bethany L; Ntaganira, Joseph; Freeman, Michael D

    2015-02-01

    In Rwanda, an estimated one million people were killed during the 1994 genocide, leaving the country shattered and social fabric destroyed. Large-scale traumatic events such as wars and genocides have been linked to endemic post-traumatic stress disorder, depression and suicidality. The study objective was to investigate whether the 1994 genocide exposure is associated with suicide in Rwanda. We conducted a population-based case-control study. Suicide victims were matched to three living controls for sex, age and residential location. Exposure was defined as being a genocide survivor, having suffered physical/sexual abuse in the genocide, losing a first-degree relative in the genocide, having been convicted for genocide crimes or having a first-degree relative convicted for genocide. From May 2011 to May 2013, 162 cases and 486 controls were enrolled countrywide. Information was collected from the police, local village administrators and family members. After adjusting for potential confounders, having been convicted for genocide crimes was a significant predictor for suicide (OR=17.3, 95% CI 3.4 to 88.1). Being a survivor, having been physically or sexually abused during the genocide, and having lost a first-degree family member to genocide were not significantly associated with suicide. These findings demonstrate that individuals convicted for genocide crimes are experiencing continued psychological disturbances that affect their social reintegration into the community even 20 years after the event. Given the large number of genocide perpetrators reintegrated after criminal courts and Gacaca traditional reconciling trials, suicide could become a serious public health burden if preventive remedial action is not identified. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Concordance of occupational and environmental exposure information elicited from patients with Alzheimer's disease and surrogate respondents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chong, J.P.; Turpie, I.; Haines, T.

    Identification of risk factors for Alzheimer's disease through the use of well designed case-control studies has been described as a research priority. Increasing recognition of the neurotoxic potential of many industrial chemicals such as organic solvents raises the question of the occupational and environmental contribution to the etiology of this high-priority health problem. The intention of this study was to develop and evaluate a methodology that could be used in a large scale case-control study of the occupational and environmental risk factors for dementia or a population-based surveillance system for neurotoxic disorders. The specific objectives of this study were tomore » investigate: (1) the reliability of exposure-eliciting, interviewer-administered questionnaires given to patients with Alzheimer's disease (SDAT); (2) the reliability of exposure-eliciting interviewer-administered questionnaires given to the family of patients with SDAT and the agreement with the responses of the patient or surrogate respondents; (3) the reliability and agreement of responses of age- and sex-matched control patients and their families selected from geriatric care institutions and the community, with respect to the same exposure-eliciting and interviewer-administered questionnaire; and (4) the reliability of agent-based exposure ascertainment by a single, trained rater. The results of the study demonstrate that occupational and environmental histories from which exposure information can be derived is most reliably elicited from job descriptions of cases and control subjects rather than job titles alone or detailed probes for potential neurotoxic exposures. This will necessitate the use of standardized interviewer-administered instruments to derive this information in case-control studies of Alzheimer's disease or population-based surveillance systems for occupational and environmental neurotoxicity.« less

  9. Field-based random sampling without a sampling frame: control selection for a case-control study in rural Africa.

    PubMed

    Crampin, A C; Mwinuka, V; Malema, S S; Glynn, J R; Fine, P E

    2001-01-01

    Selection bias, particularly of controls, is common in case-control studies and may materially affect the results. Methods of control selection should be tailored both for the risk factors and disease under investigation and for the population being studied. We present here a control selection method devised for a case-control study of tuberculosis in rural Africa (Karonga, northern Malawi) that selects an age/sex frequency-matched random sample of the population, with a geographical distribution in proportion to the population density. We also present an audit of the selection process, and discuss the potential of this method in other settings.

  10. Familial aggregation of age-related macular degeneration in the Utah population.

    PubMed

    Luo, Ling; Harmon, Jennifer; Yang, Xian; Chen, Haoyu; Patel, Shrena; Mineau, Geraldine; Yang, Zhenglin; Constantine, Ryan; Buehler, Jeanette; Kaminoh, Yuuki; Ma, Xiang; Wong, Tien Y; Zhang, Maonian; Zhang, Kang

    2008-02-01

    We examined familial aggregation and risk of age-related macular degeneration in the Utah population using a population-based case-control study. Over one million unique patient records were searched within the University of Utah Health Sciences Center and the Utah Population Database (UPDB), identifying 4764 patients with AMD. Specialized kinship analysis software was used to test for familial aggregation of disease, estimate the magnitude of familial risks, and identify families at high risk for disease. The population-attributable risk (PAR) for AMD was calculated to be 0.34. Recurrence risks in relatives indicate increased relative risks in siblings (2.95), first cousins (1.29), second cousins (1.13), and parents (5.66) of affected cases. There were 16 extended large families with AMD identified for potential use in genetic studies. Each family had five or more living affected members. The familial aggregation of AMD shown in this study exemplifies the merit of the UPDB and supports recent research demonstrating significant genetic contribution to disease development and progression.

  11. Risk factors and therapy for goat mastitis in a hospital-based case-control study in Bangladesh.

    PubMed

    Koop, Gerrit; Islam, Md Nurul; Rahman, Md Mizanur; Khatun, Momena; Ferdous, Jinnat; Sayeed, Md Abu; Islam, Shariful; Ahaduzzaman, Md; Akter, Sazeda; Mannan, Abdul; Hassan, Mohammad Mahmudul; Dissanayake, Ravi; Hoque, Md Ahasanul

    2016-02-01

    Bangladesh has a large population of goats, which contribute to the income, nutrition and welfare of the households of many families. Mastitis in goats has a low incidence, but is often very severe, making veterinary care necessary. The aim of this study was to identify seasonality and risk factors for goat mastitis in a hospital-based matched case-control study in a teaching veterinary hospital in Chittagong, Bangladesh and to describe the range of antimicrobial treatments applied in this situation. Cases of mastitis and controls were drawn from the hospital patient recording system, along with their risk factor status. Multiple imputation was applied to deal with the missing values in the data analysis. Mastitis occurred somewhat more in the rainy season, and comprised about 3% of all goats admitted to the hospital during January 2011-June 2014. Free-ranging farming system, poor body condition score and non-native goat breeds were significantly associated with case status. Treatment of clinical mastitis was variable and unsystematic, but the use of gentamicin was commonly recorded. The need for more prudent and evidence-based antimicrobial therapies is discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. A multi-site evaluation of innovative approaches to increase tuberculosis case notification: summary results.

    PubMed

    Creswell, Jacob; Sahu, Suvanand; Blok, Lucie; Bakker, Mirjam I; Stevens, Robert; Ditiu, Lucica

    2014-01-01

    Globally, TB notifications have stagnated since 2007, and sputum smear positive notifications have been declining despite policies to improve case detection. We evaluate results of 28 interventions focused on improving TB case detection. We measured additional sputum smear positive cases treated, defined as the intervention area's increase in case notification during the project compared to the previous year. Projects were encouraged to select control areas and collect historical notification data. We used time series negative binomial regression for over-dispersed cross-sectional data accounting for fixed and random effects to test the individual projects' effects on TB notification while controlling for trend and control populations. Twenty-eight projects, 19 with control populations, completed at least four quarters of case finding activities, covering a population of 89.2 million. Among all projects sputum smear positive (SS+) TB notifications increased 24.9% and annualized notification rates increased from 69.1 to 86.2/100,000 (p = 0.0209) during interventions. Among the 19 projects with control populations, SS+TB case notifications increased 36.9% increase while in the control populations a 3.6% decrease was observed. Fourteen (74%) of the 19 projects' SS+TB notification rates in intervention areas increased from the baseline to intervention period when controlling for historical trends and notifications in control areas. Interventions were associated with large increases in TB notifications across many settings, using an array of interventions. Many people with TB are not reached using current approaches. Different methods and interventions tailored to local realities are urgently needed.

  13. Genetic Risk Score of NOS Gene Variants Associated with Myocardial Infarction Correlates with Coronary Incidence across Europe

    PubMed Central

    Carreras-Torres, Robert; Kundu, Suman; Zanetti, Daniela; Esteban, Esther

    2014-01-01

    Coronary artery disease (CAD) mortality and morbidity is present in the European continent in a four-fold gradient across populations, from the South (Spain and France) with the lowest CAD mortality, towards the North (Finland and UK). This observed gradient has not been fully explained by classical or single genetic risk factors, resulting in some cases in the so called Southern European or Mediterranean paradox. Here we approached population genetic risk estimates using genetic risk scores (GRS) constructed with single nucleotide polymorphisms (SNP) from nitric oxide synthases (NOS) genes. These SNPs appeared to be associated with myocardial infarction (MI) in 2165 cases and 2153 controls. The GRSs were computed in 34 general European populations. Although the contribution of these GRS was lower than 1% between cases and controls, the mean GRS per population was positively correlated with coronary incidence explaining 65–85% of the variation among populations (67% in women and 86% in men). This large contribution to CAD incidence variation among populations might be a result of colinearity with several other common genetic and environmental factors. These results are not consistent with the cardiovascular Mediterranean paradox for genetics and support a CAD genetic architecture mainly based on combinations of common genetic polymorphisms. Population genetic risk scores is a promising approach in public health interventions to develop lifestyle programs and prevent intermediate risk factors in certain subpopulations with specific genetic predisposition. PMID:24806096

  14. A population-based case-control teratologic study of furazidine, a nitrofuran-derivative treatment during pregnancy.

    PubMed

    Czeizel, A E; Rockenbauer, M; Sørensen, H T; Olsen, J

    2000-04-01

    To study human teratogenic potential of furazidine treatment during pregnancy. Pair analysis of cases with congenital abnormalities and matched population controls. The Hungarian Case-Control Surveillance of Congenital Abnormalities. 38,151 pregnant women who had newborn infants without any defects (population control group) and 22,865 pregnant women who had newborns or fetuses with congenital abnormalities between 1980 and 1996. In the case group, 157 (0.7%) and in the control group, 254 (0.7%) pregnant women were treated with furazidine. The case-control pair analysis did not indicate a teratogenic potential of furazidine use during the second to third months of gestation, i.e. in the critical period for major congenital abnormalities. Treatment with furazidine during pregnancy did not show teratogenic risk to the fetus.

  15. A coccidioidomycosis outbreak following the Northridge, Calif, earthquake

    USGS Publications Warehouse

    Schneider, E.; Hajjeh, R.A.; Spiegel, R.A.; Jibson, R.W.; Harp, E.L.; Marshall, G.A.; Gunn, R.A.; McNeil, M.M.; Pinner, R.W.; Baron, R.C.; Burger, R.C.; Hutwagner, L.C.; Crump, C.; Kaufman, L.; Reef, S.E.; Feldman, G.M.; Pappagianis, D.; Werner, S.B.

    1997-01-01

    Objective. - To describe a coccidioidomycosis outbreak in Ventura County following the January 1994 earthquake, centered in Northridge, Calif, and to identify factors that increased the risk for acquiring acute coccidioidomycosis infection. Design. - Epidemic investigation, population- based skin test survey, and case-control study. Setting. - Ventura County, California. Results. - In Ventura County, between January 24 and March 15, 1994, 203 outbreak-associated coccidioidomycosis cases, including 3 fatalities, were identified (attack rate [AR], 30 cases per 100 000 population). The majority of cases (56%) and the highest AR (114 per 100 000 population) occurred in the town of Simi Valley, a community located at the base of a mountain range that experienced numerous landslides associated with the earthquake. Disease onset for cases peaked 2 weeks after the earthquake. The AR was 2.8 times greater for persons 40 years of age and older than for younger persons (relative risk, 2.8; 95% confidence interval [CI], 2.1-3.7; P<.001). Environmental data indicated that large dust clouds, generated by landslides following the earthquake and strong aftershocks in the Santa Susana Mountains north of Simi Valley, were dispersed into nearby valleys by northeast winds. Simi Valley case-control study data indicated that physically being in a dust cloud (odds ratio, 3.0; 95% CI, 1.6-5.4; P<.001) and time spent in a dust cloud (P<.001) significantly increased the risk for being diagnosed with acute coccidioidomycosis. Conclusions. - Both the location and timing of cases strongly suggest that the coccidioidomycosis outbreak in Ventura County was caused when arthrospores were spread in dust clouds generated by the earthquake. This is the first report of a coccidioidomycosis outbreak following an earthquake. Public and physician awareness, especially in endemic areas following similar dust cloud- generating events, may result in prevention and early recognition of acute coccidioidomycosis.

  16. Lysenkoism and the population control movement.

    PubMed

    Simon, J L

    1997-09-01

    The case of Lysenkoism in the Soviet Union helps us understand how people's wrong beliefs can be influenced by what the information they receive from outside, especially when there is a large volume of media coverage and there is no contrary information to be heard. The population control movement in contemporary United States has many parallels to the Lysenko episode.

  17. Dietary patterns and colorectal cancer: results from a Canadian population-based study.

    PubMed

    Chen, Zhi; Wang, Peizhong Peter; Woodrow, Jennifer; Zhu, Yun; Roebothan, Barbara; Mclaughlin, John R; Parfrey, Patrick S

    2015-01-15

    The relationship between major dietary patterns and colorectal cancer (CRC) in other populations largely remains consistent across studies. The objective of the present study is to assess if dietary patterns are associated with the risk of CRC in the population of Newfoundland and Labrador (NL). Data from a population based case-control study in the province of NL were analyzed, including 506 CRC patients (306 men and 200 women) and 673 controls (400 men and 273 women), aged 20-74 years. Dietary habits were assessed by a 169-item food frequency questionnaire (FFQ). Logistic regression analyses were performed to investigate the association between dietary patterns and the CRC risk. Three major dietary patterns were derived using factor analysis, namely a Meat-diet pattern, a Plant-based diet pattern and a Sugary-diet pattern. In combination the three dietary patterns explained 74% of the total variance in food intake. Results suggest that the Meat-diet and the Sugary-diet increased the risk of CRC with corresponding odds ratios (ORs) of 1.84 (95% CI: 1.19-2.86) and 2.26 (95% CI: 1.39-3.66) for people in the highest intake quintile compared to those in the lowest. Whereas plant-based diet pattern decreases the risk of CRC with a corresponding OR of 0.55 (95% CI: 0.35-0.87). Even though odds ratios (ORs) were not always statistically significant, largely similar associations across three cancer sites were found: the proximal colon, the distal colon, and the rectum. The finding that Meat-diet/Sugary-diet patterns increased and Plant-based diet pattern decreased the risk of CRC would guide the promotion of healthy eating for primary prevention of CRC in this population.

  18. Higher risk of orofacial clefts in children born to mothers with angina pectoris: a population-based case-control study.

    PubMed

    Czeizel, Andrew E; Vereczkey, Attila; Bánhidy, Ferenc

    2015-02-01

    Previously an unexpected association of maternal angina pectoris (MAP) during pregnancy with a higher risk of orofacial clefts in their children was found. There were three objectives of this study: (i) to evaluate the validity of MAP-diagnoses in the previous study and the recent history of mothers with MAP in a follow-up study; (ii) to estimate the prevalence of other congenital abnormalities in the offspring of mothers with MAP; and (iii) to analyze the possible effect of confounders for the risk of orofacial clefts. The large dataset of population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities, 1980-1996 was evaluated including 22 843 cases with congenital abnormalities and 38 151 controls without any defect. Twenty-two cases (0.10%) and 12 controls (0.03%) were born to mothers with medically recorded MAP (odds ratio [OR] with 95% confidence interval [CI]: 3.7, 1.8-7.3). Of 22 cases, six had isolated cleft lip ± palate (OR with 95% CI: 13.3, 4.9-35.9) and two were affected with isolated cleft palate (OR with 95% CI: 10.5, 2.3-47.6). The diagnosis of MAP was confirmed in seven women visited at home in 2009-2010, two had recent myocardial infarction and five were smokers. There was no higher risk for other congenital abnormalities. In conclusion the higher risk of orofacial clefts was confirmed in the children of mothers with MAP and smoking may trigger the genetic predisposition of both MAP and orofacial clefts. However, the number of cases was limited and therefore further studies are needed to confirm or reject this theoretically and practically important observation. © 2014 Japanese Teratology Society.

  19. Neuropsychologic assessment of a population-based sample of Gulf War veterans.

    PubMed

    Wallin, Mitchell T; Wilken, Jeffrey; Alfaro, Mercedes H; Rogers, Catherine; Mahan, Clare; Chapman, Julie C; Fratto, Timothy; Sullivan, Cynthia; Kang, Han; Kane, Robert

    2009-09-01

    The objective of this project was to compare neuropsychologic performance and quality of life in a population-based sample of deployed Gulf War (GW) veterans with and without multisymptom complaints. The study participants were obtained from the 30,000 member population-based National Health Survey of GW-era veterans conducted in 1995. Cases (N=25) were deployed to the year 1990 and 1991 GW and met Center for Disease Control and Prevention criteria for multisymptom GW illness (GWI). Controls (N=16) were deployed to the 1990 and 1991 GW but did not meet Center for Disease Control and Prevention criteria for GWI. There were no significant differences in composite scores on the traditional and computerized neuropsychologic battery (automated neuropsychologic assessment metrics) between GW cases and controls using bivariate techniques. Multiple linear regression analyses controlling for demographic and clinical variables revealed composite automated neuropsychologic assessment metrics scores were associated with age (b=-7.8; P=0.084), and education (b=22.9; P=0.0012), but not GW case or control status (b=-63.9; P=0.22). Compared with controls, GW cases had significantly more impairment on the Personality Assessment Inventory and the short form-36. Compared with GW controls, GW cases meeting criteria for GWI had preserved cognition function but had significant psychiatric symptoms and lower quality of life.

  20. Association between glioma and history of allergies, asthma, and eczema: a case-control study with three groups of controls

    PubMed Central

    Il’yasova, Dora; McCarthy, Bridget; Marcello, Jennifer; Schildkraut, Joellen M.; Moorman, Patricia G.; Krishnamachari, Bhuma; Ali-Osman, Francis; Bigner, Darell D.; Davis, Faith

    2009-01-01

    Because glioma etiology is largely unknown, the inverse association of glioma risk with atopic conditions is promising and deserves close scrutiny. We examined the association between a history of allergies, asthma, and eczema and glioma risk using sibling, friend, and clinic-based controls. This analysis included 388 incident glioma cases and 80 sibling, 191 friend, and 177 clinic-based controls. Each subject’s medical history was assessed via a web-based or telephone survey. Odds ratios (ORs) and their 95% confidence intervals for the associations with allergies, asthma, eczema, and the overall number of these conditions were calculated from conditional (for sibling and friend controls) and unconditional (for clinic-based controls) logistic models. Allergies were consistently inversely associated with the glioma: ORs were 0.53 (95% CI, 0.15–1.84), 0.54 (95% CI, 0.28–1.07), and 0.34 (95% CI, 0.23–0.50) with sibling, friend, and clinic-based controls, respectively. Asthma showed an inverse association only in the comparison with sibling controls (OR=0.43; 95% CI, 0.19–1.00). Eczema showed an inverse association only in the comparison with friend controls (OR=0.42; 95% CI, 0.15–1.18). The overall number of these conditions (ordinal score 0, 1, 2, 3) was inversely associated with glioma: The risk decreased 31–45% with each addition of an atopic condition. These estimates were the most stable when different control groups were considered. Comparing the prevalence of these conditions in the three control groups with published data, we note that clinic-based controls generally better approximate the prevalence data for population-based groups. These controls appear to present a reasonable choice for clinic-centered case-control studies. PMID:19336556

  1. Extension of traditional infectious disease surveillance with a repeated population survey.

    PubMed

    Friesema, Ingrid H M; van Gageldonk-Lafeber, Arianne B; van Pelt, Wilfrid

    2015-02-01

    Public health surveillance is an important tool for monitoring cases of infectious diseases. Identification of risk factors requires the comparison of exposure between cases and controls. However, standard surveillance systems do not routinely collect information on controls. Since 2008, we have extended the surveillance of infectious diseases in The Netherlands with a repeated population survey. This survey is based on the thrice-yearly administration of a questionnaire about potential risk factors for several gastrointestinal, foodborne and respiratory infections to a representative, dynamic sample of the Dutch population. The questionnaire contains questions similar to those used for interviewing cases. Over 14 mailing rounds, 4926 persons were approached with a response of 36%, with a small underrepresentation of men, young people, people living in large cities and persons with both parents born outside The Netherlands. Costs per completed questionnaire were around 15 euro. Muscle/joint pain in the past 4 weeks was the most reported symptom (44%), followed by running nose (39%) and headache (32%); 5.6% reported gastroenteritis, reflecting an incidence of 997 episodes per 1000 person-years. Extending traditional surveillance with a repeated population survey offers the unique opportunity to gather data for a multitude of purposes. The survey already has been used in two outbreak investigations and two case-control studies. It is cost-effective and may provide novel epidemiological insights towards risk group and risk factor identification and characterization for a variety of infectious diseases. The survey will be continued and expanded in use. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  2. Driver sleepiness and risk of motor vehicle crash injuries: a population-based case control study in Fiji (TRIP 12).

    PubMed

    Herman, Josephine; Kafoa, Berlin; Wainiqolo, Iris; Robinson, Elizabeth; McCaig, Eddie; Connor, Jennie; Jackson, Rod; Ameratunga, Shanthi

    2014-03-01

    Published studies investigating the role of driver sleepiness in road crashes in low and middle-income countries have largely focused on heavy vehicles. We investigated the contribution of driver sleepiness to four-wheel motor vehicle crashes in Fiji, a middle-income Pacific Island country. The population-based case control study included 131 motor vehicles involved in crashes where at least one person died or was hospitalised (cases) and 752 motor vehicles identified in roadside surveys (controls). An interviewer-administered questionnaire completed by drivers or proxies collected information on potential risks for crashes including sleepiness while driving, and factors that may influence the quantity or quality of sleep. Following adjustment for confounders, there was an almost six-fold increase in the odds of injury-involved crashes for vehicles driven by people who were not fully alert or sleepy (OR 5.7, 95%CI: 2.7, 12.3), or those who reported less than 6 h of sleep during the previous 24 h (OR 5.9, 95%CI: 1.7, 20.9). The population attributable risk for crashes associated with driving while not fully alert or sleepy was 34%, and driving after less than 6 h sleep in the previous 24 h was 9%. Driving by people reporting symptoms suggestive of obstructive sleep apnoea was not significantly associated with crash risk. Driver sleepiness is an important contributor to injury-involved four-wheel motor vehicle crashes in Fiji, highlighting the need for evidence-based strategies to address this poorly characterised risk factor for car crashes in less resourced settings. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Night shift work, chronotype and prostate cancer risk in the MCC-Spain case-control study.

    PubMed

    Papantoniou, Kyriaki; Castaño-Vinyals, Gemma; Espinosa, Ana; Aragonés, Nuria; Pérez-Gómez, Beatriz; Burgos, Javier; Gómez-Acebo, Inés; Llorca, Javier; Peiró, Rosana; Jimenez-Moleón, Jose Juan; Arredondo, Francisco; Tardón, Adonina; Pollan, Marina; Kogevinas, Manolis

    2015-09-01

    Night shift work has been classified as a probable human carcinogen based on experimental studies and limited human evidence on breast cancer. Evidence on other common cancers, such as prostate cancer, is scarce. Chronotype is an individual characteristic that may relate to night work adaptation. We evaluated night shift work with relation to prostate cancer, taking into account chronotype and disease severity in a population based case-control study in Spain. We included 1,095 prostate cancer cases and 1,388 randomly selected population controls. We collected detailed information on shift schedules (permanent vs. rotating, time schedules, duration, frequency), using lifetime occupational history. Sociodemographic and lifestyle factors were assessed by face-to-face interviews and chronotype through a validated questionnaire. We used unconditional logistic regression analysis adjusting for potential confounders. Subjects who had worked at least for one year in night shift work had a slightly higher prostate cancer risk [Odds Ratio (OR) 1.14; 95%CI 0.94, 1.37] compared with never night workers; this risk increased with longer duration of exposure (≥ 28 years: OR 1.37; 95%CI 1.05, 1.81; p-trend = 0.047). Risks were more pronounced for high risk tumors [D'Amico classification, Relative Risk Ratio (RRR) 1.40; 95%CI 1.05, 1.86], particularly among subjects with longer duration of exposure (≥28 years: RRR 1.63; 95%CI 1.08, 2.45; p-trend = 0.027). Overall risk was higher among subjects with an evening chronotype, but also increased in morning chronotypes after long-term night work. In this large population based study, we found an association between night shift work and prostate cancer particularly for tumors with worse prognosis. © 2014 UICC.

  4. Colon Cancer Family Registry: an international resource for studies of the genetic epidemiology of colon cancer.

    PubMed

    Newcomb, Polly A; Baron, John; Cotterchio, Michelle; Gallinger, Steve; Grove, John; Haile, Robert; Hall, David; Hopper, John L; Jass, Jeremy; Le Marchand, Loïc; Limburg, Paul; Lindor, Noralane; Potter, John D; Templeton, Allyson S; Thibodeau, Steve; Seminara, Daniela

    2007-11-01

    Family studies have served as a cornerstone of genetic research on colorectal cancer. The Colorectal Cancer Family Registry (Colon CFR) is an international consortium of six centers in North America and Australia formed as a resource to support studies on the etiology, prevention, and clinical management of colorectal cancer. Differences in design and sampling schemes ensures a resource that covers the continuum of disease risk. Two separate recruitment strategies identified colorectal cancer cases: population-based (incident case probands identified by cancer registries; all six centers) and clinic-based (families with multiple cases of colorectal cancer presenting at cancer family clinics; three centers). At this time, the Colon CFR is in year 10 with the second phase of enrollment nearly complete. In phase I recruitment (1998-2002), population-based sampling ranged from all incident cases of colorectal cancer to a subsample based on age at diagnosis and/or family cancer history. During phase II (2002-2007), population-based recruitment targeted cases diagnosed before the age of 50 years are more likely attributable to genetic factors. Standardized protocols were used to collect information regarding family cancer history and colorectal cancer risk factors, and biospecimens were obtained to assess microsatellite instability (MSI) status, expression of mismatch repair proteins, and other molecular and genetic processes. Of the 8,369 case probands enrolled to date, 2,602 reported having one or more colorectal cancer-affected relatives and 799 met the Amsterdam I criteria for Lynch syndrome. A large number of affected (1,324) and unaffected (19,816) relatives were enrolled, as were population-based (4,108) and spouse (983) controls. To date, 91% of case probands provided blood (or, for a few, buccal cell) samples and 75% provided tumor tissue. For a selected sample of high-risk subjects, lymphocytes have been immortalized. Nearly 600 case probands had more than two affected colorectal cancer relatives, and 800 meeting the Amsterdam I criteria and 128, the Amsterdam II criteria. MSI testing for 10 markers was attempted on all obtained tumors. Of the 4,011 tumors collected in phase I that were successfully tested, 16% were MSI-high, 12% were MSI-low, and 72% were microsatellite stable. Tumor tissues from clinic-based cases were twice as likely as population-based cases to be MSI-high (34% versus 17%). Seventeen percent of phase I proband tumors and 24% of phase II proband tumors had some loss of mismatch repair protein, with the prevalence depending on sampling. Active follow-up to update personal and family histories, new neoplasms, and deaths in probands and relatives is nearly complete. The Colon CFR supports an evolving research program that is broad and interdisciplinary. The greater scientific community has access to this large and well-characterized resource for studies of colorectal cancer.

  5. Aircraft, road and railway traffic noise as risk factors for heart failure and hypertensive heart disease-A case-control study based on secondary data.

    PubMed

    Seidler, Andreas; Wagner, Mandy; Schubert, Melanie; Dröge, Patrik; Römer, Karin; Pons-Kühnemann, Jörn; Swart, Enno; Zeeb, Hajo; Hegewald, Janice

    2016-11-01

    Several studies point to an elevated risk for cardiovascular diseases induced by traffic noise. We examined the association between aircraft, road traffic and railway noise and heart failure or hypertensive heart disease (HHD) in a large case-control study. The study population consisted of individuals that were insured by three large statutory health insurance funds in the Rhine-Main area of Germany. Based on insurance claims and prescription data, 104,145 cases of heart failure or HHD diagnosed 2006-10 were identified and compared with 654,172 control subjects. Address-specific exposure to aircraft, road and railway traffic noise in 2005 was estimated. Odds Ratios were calculated using logistic regression analysis, adjusted for age, sex, local proportion of persons receiving unemployment benefits, and individual socioeconomic status (available for 39% of the individuals). A statistically significant linear exposure-risk relationship with heart failure or hypertensive heart disease was found for aircraft traffic noise (1.6% risk increase per 10dB increase in the 24-h continuous noise level; 95% CI 0.3-3.0%), road traffic noise (2.4% per 10dB; 95% CI 1.6-3.2%), and railway noise (3.1% per 10dB; 95% CI 2.2-4.1%). For individuals with 24-h continuous aircraft noise levels <40dB and nightly maximum aircraft noise levels exceeding 50dB six or more times, a significantly increased risk was observed. In general, risks of HHD were considerably higher than the risks of heart failure. Regarding the high prevalence of traffic noise from various sources, even low risk increases for frequent diseases are relevant for the population as a whole. Copyright © 2016 Elsevier GmbH. All rights reserved.

  6. Contribution of Established Stroke Risk Factors to the Burden of Stroke in Young Adults.

    PubMed

    Aigner, Annette; Grittner, Ulrike; Rolfs, Arndt; Norrving, Bo; Siegerink, Bob; Busch, Markus A

    2017-07-01

    As stroke in young adults is assumed to have different etiologies and risk factors than in older populations, the aim of this study was to examine the contribution of established potentially modifiable cardiovascular risk factors to the burden of stroke in young adults. A German nationwide case-control study based on patients enrolled in the SIFAP1 study (Stroke In Young Fabry Patients) 2007 to 2010 and controls from the population-based GEDA study (German Health Update) 2009 to 2010 was performed. Cases were 2125 consecutive patients aged 18 to 55 years with acute first-ever stroke from 26 clinical stroke centers; controls (age- and sex-matched, n=8500, without previous stroke) were from a nationwide community sample. Adjusted population-attributable risks of 8 risk factors (hypertension, hyperlipidemia, diabetes mellitus, coronary heart disease, smoking, heavy episodic alcohol consumption, low physical activity, and obesity) and their combinations for all stroke, ischemic stroke, and primary intracerebral hemorrhage were calculated. Low physical activity and hypertension were the most important risk factors, accounting for 59.7% (95% confidence interval, 56.3-63.2) and 27.1% (95% confidence interval, 23.6-30.6) of all strokes, respectively. All 8 risk factors combined explained 78.9% (95% confidence interval, 76.3-81.4) of all strokes. Population-attributable risks of all risk factors were similar for all ischemic stroke subtypes. Population-attributable risks of most risk factors were higher in older age groups and in men. Modifiable risk factors previously established in older populations also account for a large part of stroke in younger adults, with 4 risk factors explaining almost 80% of stroke risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583. © 2017 American Heart Association, Inc.

  7. The c.553G>T Genetic Variant of the APOA5 Gene and Altered Triglyceride Levels in the Asian Population: A Meta-Analysis of Case-Control Studies.

    PubMed

    He, Hongjuan; Lei, Lei; Chen, Erfei; Dong, Jing; Zhang, Kejin; Yang, Jin

    2016-12-01

    To explore the association of the APOA5 gene c.553G>T polymorphism with hypertriglyceridemia (HTG) susceptibility and altered triglyceride levels. We searched the PubMed, Google Scholar, and CNKI databases for published studies relating to analyses of these associations. Case-control and comparative studies of the association between the APOA5 c.553G>T variant and altered triglyceride levels were included. In total, the meta-analysis involved 10 studies on HTG, which provided 2219 cases and 3401 controls. To measure the correlation between the c.553G>T polymorphism and HTG susceptibility, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The overall OR was calculated using a random-effects model. Compared with APOA5 c.553 GG carriers, c.553T carriers displayed an increased risk of HTG in the Asian population, with an overall random effects OR of 3.55 (95% CI: 2.46-5.13) in the dominant model. There was significant heterogeneity among the studies (P heterogeneity : Chi 2  = 45.80, I 2  = 75.98%), which may be largely explained by certain patient types. Both the sensitivity analysis and publication bias suggested that the overall result was acceptable. Subgroup analysis showed a large difference in serum triglyceride levels based on the c.553 G > T polymorphism in healthy individuals and HTG patients. APOA5 c.553T carriers exhibit higher triglyceride levels than GG carriers. Our results suggest that APOA5 c. 553T is an independent risk factor for HTG and increased triglyceride levels in the Asian population. APOA5 c. 553T could be employed as a genetic risk marker for HTG and increased triglyceride levels.

  8. Virtual reality measures in neuropsychological assessment: a meta-analytic review.

    PubMed

    Neguț, Alexandra; Matu, Silviu-Andrei; Sava, Florin Alin; David, Daniel

    2016-02-01

    Virtual reality-based assessment is a new paradigm for neuropsychological evaluation, that might provide an ecological assessment, compared to paper-and-pencil or computerized neuropsychological assessment. Previous research has focused on the use of virtual reality in neuropsychological assessment, but no meta-analysis focused on the sensitivity of virtual reality-based measures of cognitive processes in measuring cognitive processes in various populations. We found eighteen studies that compared the cognitive performance between clinical and healthy controls on virtual reality measures. Based on a random effects model, the results indicated a large effect size in favor of healthy controls (g = .95). For executive functions, memory and visuospatial analysis, subgroup analysis revealed moderate to large effect sizes, with superior performance in the case of healthy controls. Participants' mean age, type of clinical condition, type of exploration within virtual reality environments, and the presence of distractors were significant moderators. Our findings support the sensitivity of virtual reality-based measures in detecting cognitive impairment. They highlight the possibility of using virtual reality measures for neuropsychological assessment in research applications, as well as in clinical practice.

  9. Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case-control study.

    PubMed

    Chan, June M; Wang, Furong; Holly, Elizabeth A

    2009-08-01

    We examined the associations between sweets, sweetened and unsweetened beverages, and sugars and pancreatic cancer risk. We conducted a population-based case-control study (532 cases, 1,701 controls) and used multivariate logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI). Because associations were often different by sex, we present results for men and women combined and separately. Among men, greater intakes of total and specific sweets were associated with pancreatic cancer risk (total sweets: OR = 1.9, 95% CI: 1.0, 3.6; sweet condiments: OR = 1.9, 95% CI: 1.2, 3.1; chocolate candy: OR = 2.4, 95% CI: 1.1, 5.0; other mixed candy bars: OR = 3.3, 95% CI: 1.5, 7.3 for 1 + servings/day versus none/rarely). Sweets were not consistently associated with risk among women. Sweetened beverages were not associated with increased pancreatic cancer risk. In contrast, low-calorie soft drinks were associated with increased risk among men only; while other low-/non-caloric beverages (e.g., coffee, tea, and water) were unassociated with risk. Of the three sugars assessed (lactose, fructose, and sucrose), only the milk sugar lactose was associated with pancreatic cancer risk (OR = 2.0, 95% CI: 1.5, 2.7 comparing extreme quartiles). These results provide limited support for the hypothesis that sweets or sugars increase pancreatic cancer risk.

  10. Analgesic and anti-inflammatory drug use and risk of bladder cancer: a population based case control study

    PubMed Central

    Fortuny, Joan; Kogevinas, Manolis; Zens, Michael S; Schned, Alan; Andrew, Angeline S; Heaney, John; Kelsey, Karl T; Karagas, Margaret R

    2007-01-01

    Background Use of phenacetin and other analgesic and non-steroidal anti-inflammatory drugs (NSAIDs) potentially influences bladder cancer incidence, but epidemiologic evidence is limited. Methods We analyzed data from 376 incident bladder cancer cases and 463 controls from a population-based case-control study in New Hampshire on whom regular use of analgesic drugs and NSAIDs was obtained. Odds ratios and 95% confidence intervals were computed using logistic regression with adjustment for potentially confounding factors. Separate models by tumor stage, grade and TP53 status were conducted. Results We found an elevated odds ratio (OR) associated with reported use of phenacetin-containing medications, especially with longer duration of use (OR >8 years = 3.00, 95% confidence interval (CI) = 1.4–6.5). In contrast, use of paracetamol did not relate overall to risk of bladder cancer. We also found that regular use of any NSAID was associated with a statistically significant decrease in bladder cancer risk (OR = 0.6, 95% CI = 0.4–0.9), and specifically use of aspirin. Further, the association with NSAID use was largely among invasive, high grade and TP53 positive tumors. Conclusion While these agents have been investigated in several studies, a number of questions remain regarding the effects of analgesic and NSAID use on risk of bladder cancer. PMID:17692123

  11. Possible association of first and high birth order of pregnant women with the risk of isolated congenital abnormalities in Hungary - a population-based case-matched control study.

    PubMed

    Csermely, Gyula; Susánszky, Éva; Czeizel, Andrew E; Veszprémi, Béla

    2014-08-01

    In epidemiological studies at the estimation of risk factors in the origin of specified congenital abnormalities in general birth order (parity) is considered as confounder. The aim of this study was to analyze the possible association of first and high (four or more) birth order with the risk of congenital abnormalities in a population-based case-matched control data set. The large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities included 21,494 cases with different isolated congenital abnormality and their 34,311 matched controls. First the distribution of birth order was compared of 24 congenital abnormality groups and their matched controls. In the second step the possible association of first and high birth order with the risk of congenital abnormalities was estimated. Finally some subgroups of neural-tube defects, congenital heart defects and abdominal wall's defects were evaluated separately. A higher risk of spina bifida aperta/cystica, esophageal atresia/stenosis and clubfoot was observed in the offspring of primiparous mothers. Of 24 congenital abnormality groups, 14 had mothers with larger proportion of high birth order. Ear defects, congenital heart defects, cleft lip± palate and obstructive defects of urinary tract had a linear trend from a lower proportion of first born cases to the larger proportion of high birth order. Birth order showed U-shaped distribution of neural-tube defects and clubfoot, i.e. both first and high birth order had a larger proportion in cases than in their matched controls. Birth order is a contributing factor in the origin of some isolated congenital abnormalities. The higher risk of certain congenital abnormalities in pregnant women with first or high birth order is worth considering in the clinical practice, e.g. ultrasound scanning. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Space-Time Analysis of Testicular Cancer Clusters Using Residential Histories: A Case-Control Study in Denmark

    PubMed Central

    Sloan, Chantel D.; Nordsborg, Rikke B.; Jacquez, Geoffrey M.; Raaschou-Nielsen, Ole; Meliker, Jaymie R.

    2015-01-01

    Though the etiology is largely unknown, testicular cancer incidence has seen recent significant increases in northern Europe and throughout many Western regions. The most common cancer in males under age 40, age period cohort models have posited exposures in the in utero environment or in early childhood as possible causes of increased risk of testicular cancer. Some of these factors may be tied to geography through being associated with behavioral, cultural, sociodemographic or built environment characteristics. If so, this could result in detectable geographic clusters of cases that could lead to hypotheses regarding environmental targets for intervention. Given a latency period between exposure to an environmental carcinogen and testicular cancer diagnosis, mobility histories are beneficial for spatial cluster analyses. Nearest-neighbor based Q-statistics allow for the incorporation of changes in residency in spatial disease cluster detection. Using these methods, a space-time cluster analysis was conducted on a population-wide case-control population selected from the Danish Cancer Registry with mobility histories since 1971 extracted from the Danish Civil Registration System. Cases (N=3297) were diagnosed between 1991 and 2003, and two sets of controls (N=3297 for each set) matched on sex and date of birth were included in the study. We also examined spatial patterns in maternal residential history for those cases and controls born in 1971 or later (N= 589 case-control pairs). Several small clusters were detected when aligning individuals by year prior to diagnosis, age at diagnosis and calendar year of diagnosis. However, the largest of these clusters contained only 2 statistically significant individuals at their center, and were not replicated in SaTScan spatial-only analyses which are less susceptible to multiple testing bias. We found little evidence of local clusters in residential histories of testicular cancer cases in this Danish population. PMID:25756204

  13. Space-time analysis of testicular cancer clusters using residential histories: a case-control study in Denmark.

    PubMed

    Sloan, Chantel D; Nordsborg, Rikke B; Jacquez, Geoffrey M; Raaschou-Nielsen, Ole; Meliker, Jaymie R

    2015-01-01

    Though the etiology is largely unknown, testicular cancer incidence has seen recent significant increases in northern Europe and throughout many Western regions. The most common cancer in males under age 40, age period cohort models have posited exposures in the in utero environment or in early childhood as possible causes of increased risk of testicular cancer. Some of these factors may be tied to geography through being associated with behavioral, cultural, sociodemographic or built environment characteristics. If so, this could result in detectable geographic clusters of cases that could lead to hypotheses regarding environmental targets for intervention. Given a latency period between exposure to an environmental carcinogen and testicular cancer diagnosis, mobility histories are beneficial for spatial cluster analyses. Nearest-neighbor based Q-statistics allow for the incorporation of changes in residency in spatial disease cluster detection. Using these methods, a space-time cluster analysis was conducted on a population-wide case-control population selected from the Danish Cancer Registry with mobility histories since 1971 extracted from the Danish Civil Registration System. Cases (N=3297) were diagnosed between 1991 and 2003, and two sets of controls (N=3297 for each set) matched on sex and date of birth were included in the study. We also examined spatial patterns in maternal residential history for those cases and controls born in 1971 or later (N= 589 case-control pairs). Several small clusters were detected when aligning individuals by year prior to diagnosis, age at diagnosis and calendar year of diagnosis. However, the largest of these clusters contained only 2 statistically significant individuals at their center, and were not replicated in SaTScan spatial-only analyses which are less susceptible to multiple testing bias. We found little evidence of local clusters in residential histories of testicular cancer cases in this Danish population.

  14. Residential traffic noise exposure and vestibular schwannoma - a Danish case-control study.

    PubMed

    Roswall, Nina; Stangerup, Sven-Eric; Cayé-Thomasen, Per; Schüz, Joachim; Johansen, Christoffer; Jensen, Steen Solvang; Raaschou-Nielsen, Ole; Sørensen, Mette

    2017-10-01

    Few risk factors for sporadic vestibular schwannoma (VS) are known. Several studies have proposed an increased risk with occupational noise exposure, whereas no studies have investigated residential traffic noise exposure as a risk factor. The present study investigated if residential traffic noise was associated with vestibular schwannoma in a large, population-based Danish case-control study. We identified 1454 VS cases, age above 30 years at diagnosis, between 1990 and 2007. For each case, we selected two random population controls, matched on sex and year of birth. Road and railway traffic noise at the residence was calculated for all present and historical addresses between 1987 and index date. Associations between traffic noise and risk for VS were estimated using conditional logistic regression, adjusted for education, disposable personal income, cohabitation status, railway noise exposure, municipal population density, and municipal income. A two-year time-weighted mean road traffic noise exposure was associated with an adjusted odds ratio of 0.92 (0.82-1.03) for developing VS, per 10 dB increment. There was no clear trend in categorical analyses. Similarly, linear and categorical analyses of residential railway noise did not suggest an association. We found no interaction with demographics, year of diagnosis, individual and municipal socioeconomic variables, and railway noise exposure. The results did not differ by tumor side, spread or size. The present study does not suggest an association between residential traffic noise and VS.

  15. Risk of Psoriasis Following Terbinafine or Itraconazole Treatment for Onychomycosis: A Population-Based Case-Control Comparative Study.

    PubMed

    Chiu, Hsien-Yi; Chang, Wei-Lun; Tsai, Tsen-Fang; Tsai, Yi-Wen; Shiu, Ming-Neng

    2018-03-01

    Several case studies have reported an association between antifungal drug use and psoriasis risk. The objective of this study was to investigate the association between terbinafine/itraconazole exposure and psoriasis incidence. Among patients with onychomycosis in the Taiwan National Health Insurance Research Database, 3831 incident psoriasis cases were identified during 2004-2010 and compared with 3831 age- and sex-matched controls with the same look-back period. Multivariate conditional logistic regression was used for the analysis. The psoriasis cases were significantly more likely than matched controls to have used terbinafine or itraconazole (59.85 vs. 42.70%, respectively; p < 0.0001). After adjusting for potential confounders and cumulative duration of antifungal drug prescription, terbinafine/itraconazole use was associated with an increased psoriasis risk (adjusted odds ratio 1.33, 95% confidence interval 1.15-1.54). The association was stronger for more recent drug exposure (adjusted odds ratio 2.96, 95% confidence interval 2.25-3.90 for ≤ 90 days before the sampling date; adjusted odds ratio 1.04, 95% confidence interval 0.89-1.22 for > 360 days). In a comparison of patients receiving terbinafine or itraconazole only, psoriasis risk was higher for itraconazole (adjusted odds ratio 1.21, 95% confidence interval 1.05-1.40). This large population-based case-control analysis showed that exposure to terbinafine or itraconazole is associated with an increased risk of incident psoriasis. The finding of an increased psoriasis risk for antifungal drug users, particularly for itraconazole, deserves attention in clinical practice although further prospective studies are necessary to confirm our findings and clarify the biological mechanisms that underlie these associations.

  16. Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    2014-01-01

    Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD). These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case-control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer's disease in seven independent case-control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer's disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer's disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer's disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.

  17. Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease.

    PubMed

    Cruchaga, Carlos; Karch, Celeste M; Jin, Sheng Chih; Benitez, Bruno A; Cai, Yefei; Guerreiro, Rita; Harari, Oscar; Norton, Joanne; Budde, John; Bertelsen, Sarah; Jeng, Amanda T; Cooper, Breanna; Skorupa, Tara; Carrell, David; Levitch, Denise; Hsu, Simon; Choi, Jiyoon; Ryten, Mina; Sassi, Celeste; Bras, Jose; Gibbs, Raphael J; Hernandez, Dena G; Lupton, Michelle K; Powell, John; Forabosco, Paola; Ridge, Perry G; Corcoran, Christopher D; Tschanz, JoAnn T; Norton, Maria C; Munger, Ronald G; Schmutz, Cameron; Leary, Maegan; Demirci, F Yesim; Bamne, Mikhil N; Wang, Xingbin; Lopez, Oscar L; Ganguli, Mary; Medway, Christopher; Turton, James; Lord, Jenny; Braae, Anne; Barber, Imelda; Brown, Kristelle; Pastor, Pau; Lorenzo-Betancor, Oswaldo; Brkanac, Zoran; Scott, Erick; Topol, Eric; Morgan, Kevin; Rogaeva, Ekaterina; Singleton, Andy; Hardy, John; Kamboh, M Ilyas; George-Hyslop, Peter St; Cairns, Nigel; Morris, John C; Kauwe, John S K; Goate, Alison M

    2014-01-23

    Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD). These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case-control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer's disease in seven independent case-control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer's disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer's disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer's disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.

  18. Assessing different measures of population-level vaccine protection using a case-control study.

    PubMed

    Ali, Mohammad; You, Young Ae; Kanungo, Suman; Manna, Byomkesh; Deen, Jacqueline L; Lopez, Anna Lena; Wierzba, Thomas F; Bhattacharya, Sujit K; Sur, Dipika; Clemens, John D

    2015-11-27

    Case-control studies have not been examined for their utility in assessing population-level vaccine protection in individually randomized trials. We used the data of a randomized, placebo-controlled trial of a cholera vaccine to compare the results of case-control analyses with those of cohort analyses. Cases of cholera were selected from the trial population followed for three years following dosing. For each case, we selected 4 age-matched controls who had not developed cholera. For each case and control, GIS was used to calculate vaccine coverage of individuals in a surrounding "virtual" cluster. Specific selection strategies were used to evaluate the vaccine protective effects. 66,900 out of 108,389 individuals received two doses of the assigned regimen. For direct protection among subjects in low vaccine coverage clusters, we observed 78% (95% CI: 47-91%) protection in a cohort analysis and 84% (95% CI: 60-94%) in case-control analysis after adjusting for confounding factors. Using our GIS-based approach, estimated indirect protection was 52% (95% CI: 10-74%) in cohort and 76% (95% CI: 47-89%) in case control analysis. Estimates of total and overall effectiveness were similar for cohort and case-control analyses. The findings show that case-control analyses of individually randomized vaccine trials may be used to evaluate direct as well as population-level vaccine protection. Copyright © 2015. Published by Elsevier Ltd.

  19. Frequency of soy food consumption and serum isoflavone concentrations among Chinese women in Shanghai.

    PubMed

    Frankenfeld, Cara L; Lampe, Johanna W; Shannon, Jackilen; Gao, Dao L; Ray, Roberta M; Prunty, Joann; Kalhorn, Thomas F; Wähälä, Kristiina; Patterson, Ruth E; Thomas, David B

    2004-09-01

    The food-frequency questionnaire (FFQ) can be an efficient tool to evaluate dietary intake in large, population-based studies, especially for specific foods. The objective of this study was to validate the assessment of soy and isoflavone (daidzein and genistein) intakes, measured by an FFQ, by comparing intakes with serum isoflavone concentrations. Soy and isoflavone intakes and serum isoflavone concentrations were determined as part of a case-control study of dietary factors and risks of benign breast disease and breast cancer. The FFQ, administered during an in-person interview, included six soy-specific line items. Blood was drawn within one week of FFQ completion. In total, 1823 women living in Shanghai, People's Republic of China. In this population, soybean milk, fresh bean curd and other bean foods were eaten once per week, and fermented bean curd, fried bean curd puff and soybeans were eaten less than once per week. A significant linear trend (P<0.01) in serum isoflavone concentrations across increasing categories of soy and isoflavone intakes was observed, indicating that soy and isoflavone intakes, measured by the FFQ, well distinguished serum isoflavone concentrations. Linear trends were also observed in both case and control groups in stratified analyses, suggesting little differential bias by case-control status. The results suggest that the FFQ provides a useful marker of soy food consumption and isoflavone exposure in this population.

  20. Socio-economic and demographic determinants affecting participation in the Swedish cervical screening program: A population-based case-control study.

    PubMed

    Broberg, Gudrun; Wang, Jiangrong; Östberg, Anna-Lena; Adolfsson, Annsofie; Nemes, Szilard; Sparén, Pär; Strander, Björn

    2018-01-01

    Cervical screening programs are highly protective for cervical cancer, but only for women attending screening procedure. Identify socio-economic and demographic determinants for non-attendance in cervical screening. Design: Population-based case-control study. Setting: Sweden. Population: Source population was all women eligible for screening. Based on complete screening records, two groups of women aged 30-60 were compared. The case group, non-attending women, (N = 314,302) had no smear registered for 6-8 years. The control group (N = 266,706) attended within 90 days of invitation. Main outcome measures: Risk of non-attendance by 9 groups of socioeconomic and demographic variables. Analysis: Unadjusted odds ratios (OR) and OR after adjustment for all variables in logistic regression models were calculated. Women with low disposable family income (adjOR 2.06; 95% confidence interval (CI) 2.01-2.11), with low education (adjOR 1.77; CI 1.73-1.81) and not cohabiting (adjOR 1.47; CI 1.45-1.50) were more likely to not attend cervical screening. Other important factors for non-attendance were being outside the labour force and receiving welfare benefits. Swedish counties are responsible for running screening programs; adjusted OR for non-participation in counties ranged from OR 4.21 (CI 4.06-4.35) to OR 0.54 (CI 0.52-0.57), compared to the reference county. Being born outside Sweden was a risk factor for non-attendance in the unadjusted analysis but this disappeared in certain large groups after adjustment for socioeconomic factors. County of residence and socio-economic factors were strongly associated with lower attendance in cervical screening, while being born in another country was of less importance. This indicates considerable potential for improvement of cervical screening attendance in several areas if best practice of routines is adopted.

  1. Myocardial infarction in Swedish subway drivers.

    PubMed

    Bigert, Carolina; Klerdal, Kristina; Hammar, Niklas; Gustavsson, Per

    2007-08-01

    Particulate matter in urban air is associated with the risk of myocardial infarction in the general population. Very high levels of airborne particles have been detected in the subway system of Stockholm, as well as in several other large cities. This situation has caused concern for negative health effects among subway staff. The aim of this study was to investigate whether there is an increased incidence of myocardial infarction among subway drivers. Data from a population-based case-control study of men aged 40-69 in Stockholm County in 1976-1996 were used. The study included all first events of myocardial infarction in registers of hospital discharges and deaths. The controls were selected randomly from the general population. National censuses were used for information on occupation. Altogether, 22 311 cases and 131 496 controls were included. Among these, 54 cases and 250 controls had worked as subway drivers. The relative risk of myocardial infarction among subway drivers was not increased. It was 0.92 [95% confidence interval (95% CI) 0.68-1.25] when the subway drivers were compared with other manual workers and 1.06 (95% CI 0.78-1.43) when the subway drivers were compared with all other gainfully employed men. Subgroup analyses indicated no influence on the risk of myocardial infarction from the duration of employment, latency time, or time since employment stopped. Subway drivers in Stockholm do not have a higher incidence of myocardial infarction than other employed persons.

  2. Genetic factors in pemphigus.

    PubMed

    Tron, François; Gilbert, Danièle; Mouquet, Hugo; Joly, Pascal; Drouot, Laurent; Makni, Sondès; Masmoudi, Hatem; Charron, Dominique; Zitouni, Mondher; Loiseau, Pascale; Ben Ayed, Mourad

    2005-06-01

    Epidemiological studies performed in different ethnic populations and family studies, notably based on a partial phenotype of the autoimmune process, indicate that genetic factors are involved in the occurrence of pemphigus. However, the precise heritability remains uncertain in the absence of twin concordance rate studies. Among the different strategies available to identify genetic factors participating in autoimmune disease susceptibility, only population studies based on case-control design have been performed in pemphigus. These studies consistently showed that MHC locus, in particular HLA class II alleles, are associated with pemphigus vulgaris and pemphigus foliaceus. Other genes of the MHC locus may also participate in disease susceptibility as shown by studies using microsatellite markers across different regions of the MHC. It is likely that other non-MHC genes are involved in the pathogenesis of pemphigus. In particular, involvement of a polymorphic variant of desmoglein 1 gene was shown to be associated with pemphigus foliaceus and to interact in an epistatic manner with MHC class II genes to contribute to the autoimmune process. Other candidate genes to which a role can be assigned in the disease pathogenesis should be considered to design case-control or family-based association studies. Genome scan studies which require a large number of multiplex families to reach statistical power, should also be considered in the endemic form of pemphigus foliaceus because of the high number of familial cases.

  3. Deciphering the evolution of herbicide resistance in weeds.

    PubMed

    Délye, Christophe; Jasieniuk, Marie; Le Corre, Valérie

    2013-11-01

    Resistance to herbicides in arable weeds is increasing rapidly worldwide and threatening global food security. Resistance has now been reported to all major herbicide modes of action despite the development of resistance management strategies in the 1990s. We review here recent advances in understanding the genetic bases and evolutionary drivers of herbicide resistance that highlight the complex nature of selection for this adaptive trait. Whereas early studied cases of resistance were highly herbicide-specific and largely under monogenic control, cases of greatest concern today generally involve resistance to multiple modes of action, are under polygenic control, and are derived from pre-existing stress response pathways. Although 'omics' approaches should enable unraveling the genetic bases of complex resistances, the appearance, selection, and spread of herbicide resistance in weed populations can only be fully elucidated by focusing on evolutionary dynamics and implementing integrative modeling efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Association of CASP9, CASP10 gene polymorphisms and tea drinking with colorectal cancer risk in the Han Chinese population.

    PubMed

    Liu, He; Jiang, Xia; Zhang, Ming-wu; Pan, Yi-feng; Yu, Yun-xian; Zhang, Shan-chun; Ma, Xin-yuan; Li, Qi-long; Chen, Kun

    2013-01-01

    The initiators caspase-9 (CASP9) and caspase-10 (CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer (CRC) susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms (SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information (NCBI) datasets and genotyped by restriction fragment length polymorphism (RFLP) assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 (odds ratio (OR)(AA+AG): 0.654, 95% confidence interval (CI): 0.406-1.055; P=0.082), rs4233532 (OR(CC): 1.667, 95% CI: 0.967-2.876; OR(CT): 1.435, 95% CI: 0.998-2.063; P=0.077), and rs2881930 (OR(CC): 0.263, 95% CI: 0.095-0.728, P=0.036) showed possible association with CRC risk. However, none of the three SNPs, rs4646077 (OR(AA+AG): 1.233, 95% CI: 0.903-1.683), rs4233532 (OR(CC): 0.892, 95% CI: 0.640-1.243; OR(CT): 1.134, 95% CI: 0.897-1.433), and rs2881930 (OR(CC): 1.096, 95% CI: 0.620-1.938; OR(CT): 1.009, 95% CI: 0.801-1.271), remained significant with CRC risk in the validation set, even after stratification for different tumor locations (colon or rectum). In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set (OR: 1.755, 95% CI: 1.319-2.334). Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC.

  5. Association of CASP9, CASP10 gene polymorphisms and tea drinking with colorectal cancer risk in the Han Chinese population*

    PubMed Central

    Liu, He; Jiang, Xia; Zhang, Ming-wu; Pan, Yi-feng; Yu, Yun-xian; Zhang, Shan-chun; Ma, Xin-yuan; Li, Qi-long; Chen, Kun

    2013-01-01

    The initiators caspase-9 (CASP9) and caspase-10 (CASP10) are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer (CRC) susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms (SNPs) in CASP9 and CASP10 were chosen based on HapMap and the National Center of Biotechnology Information (NCBI) datasets and genotyped by restriction fragment length polymorphism (RFLP) assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 (odds ratio (OR)AA+AG: 0.654, 95% confidence interval (CI): 0.406–1.055; P=0.082), rs4233532 (ORCC: 1.667, 95% CI: 0.967–2.876; ORCT: 1.435, 95% CI: 0.998–2.063; P=0.077), and rs2881930 (ORCC: 0.263, 95% CI: 0.095–0.728, P=0.036) showed possible association with CRC risk. However, none of the three SNPs, rs4646077 (ORAA+AG: 1.233, 95% CI: 0.903–1.683), rs4233532 (ORCC: 0.892, 95% CI: 0.640–1.243; ORCT: 1.134, 95% CI: 0.897–1.433), and rs2881930 (ORCC: 1.096, 95% CI: 0.620–1.938; ORCT: 1.009, 95% CI: 0.801–1.271), remained significant with CRC risk in the validation set, even after stratification for different tumor locations (colon or rectum). In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set (OR: 1.755, 95% CI: 1.319–2.334). Our results found that polymorphisms of CASP9 and CASP10 genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC. PMID:23303631

  6. Jiangsu Four Cancers Study: a large case-control study of lung, liver, stomach, and esophageal cancers in Jiangsu Province, China.

    PubMed

    Zhao, Jin-Kou; Wu, Ming; Kim, Claire H; Jin, Zi-Yi; Zhou, Jin-Yi; Han, Ren-Qiang; Yang, Jie; Zhang, Xiao-Feng; Wang, Xu-Shan; Liu, Ai-Ming; Gu, Xiaoping; Su, Ming; Hu, Xu; Sun, Zheng; Li, Gang; Li, Liming; Mu, Lina; Zhang, Zuo-Feng

    2017-07-01

    Cancer is a major public health burden both globally and in China. The most common cancer-related deaths in China are attributable to cancers of the lung, liver, stomach, and esophagus. Previous epidemiologic studies on cancer in China have often been limited by small sample sizes, inconsistent measurements, and lack of precise and accurate data. The Jiangsu Four Cancers (JFC) Study is a population-based case-control study carried out in an effort to obtain consistent and high-quality data to investigate the life style, behavioral, environmental, and genetic factors associated with the four major cancers in China. The aim of this paper is to describe the overall design of the JFC Study and report selected findings on the major risk factors for cancers. Epidemiologic data were collected from 2003 to 2010 through in-person interviews using a structured questionnaire and blood samples were drawn. Unconditional logistic regression was used to estimate the associations of putative risk factors with risks of cancers of the lung, liver, stomach, and esophagus. The study included 2871 lung cancer cases, 2018 liver cancer cases, 2969 esophageal cancer cases, 2216 stomach cancer cases, and 8019 community controls. Low educational level, low income level, tobacco smoking, alcohol drinking, and family history of cancer were confirmed as risk factors for these major cancers. The JFC Study is one of the largest case-control studies of cancers in the Chinese population and will serve as a rich resource for future research on the four major cancers in China.

  7. Sarcoma risk and dioxin emissions from incinerators and industrial plants: a population-based case-control study (Italy)

    PubMed Central

    Zambon, Paola; Ricci, Paolo; Bovo, Emanuela; Casula, Alessandro; Gattolin, Massimo; Fiore, Anna Rita; Chiosi, Francesco; Guzzinati, Stefano

    2007-01-01

    Background It is not clear whether environmental exposure to dioxin affects the general population. The aim of this research is to evaluate sarcoma risk in relation to the environmental pollution caused by dioxin emitted by waste incinerators and industrial sources of airborne dioxin. The study population lives in a part of the Province of Venice (Italy), where a population-based cancer registry (Veneto Tumour Registry – RTV) has been active since 1987. Methods Two hundred and five cases of visceral and extravisceral sarcoma, confirmed by microscopic examination, diagnosed from 01.01.1990 to 31.12.1996, were extracted from the RTV database. Diagnoses were revised using the actual pathology reports and clinical records. For each sarcoma case, three controls of the same age and sex were randomly selected from the population files of the Local Health Units (LHUs). The residential history of each subject, whether case or control, was reconstructed, address by address, from 1960 to the date of diagnosis. All waste incinerators and industrial sources of airborne dioxin in the Province of Venice were taken into account, as was one very large municipal waste incinerator outside the area but close to its boundaries. The Industrial Source Complex Model in Long Term mode, version 3 (ISCLT3), was used to assess the level of atmospheric dispersion. A specific value for exposure was calculated for each point (geo-referenced address) and for each calendar year; the exposure value for each subject is expressed as the average of specific time-weighted values. The analysis takes into account 172 cases and 405 controls, aged more than 14 years. Results The risk of developing a sarcoma is 3.3 times higher (95% Confidence Interval – 95% CI: 1.24 – 8.76) among subjects, both sexes, with the longest exposure period and the highest exposure level ; a significant excess of risk was also observed in women (Odds Ratio OR = 2.41, 95% CI: 1.04 – 5.59) and for cancers of the connective and other soft tissue (International Classification of Diseases, ninth Revision – ICD-IX 171), both sexes (OR = 3.27, 95% CI: 1.35 – 7.93). Conclusion Our study supports the association between modelled dioxin exposure and sarcoma risk. PMID:17634118

  8. Elucidating the mechanisms of paternal non-disjunction of chromosome 21 in humans.

    PubMed

    Savage, A R; Petersen, M B; Pettay, D; Taft, L; Allran, K; Freeman, S B; Karadima, G; Avramopoulos, D; Torfs, C; Mikkelsen, M; Hassold, T J; Sherman, S L

    1998-08-01

    Paternal non-disjunction of chromosome 21 accounts for 5-10% of Down syndrome cases, therefore, relative to the maternally derived cases, little is known about paternally derived trisomy 21. We present the first analysis of recombination and non-disjunction for a large paternally derived population of free trisomy 21 conceptuses ( n = 67). Unlike maternal cases where the ratio of meiosis I (MI) to meiosis II (MII) errors is 3:1, a near 1:1 ratio exists among paternal cases, with a slight excess of MII errors. We found no paternal age effect for the overall population nor when classifying cases according to stage of non-disjunction error. Among 22 MI cases, only five had an observable recombinant event. This differs significantly from the 11 expected events ( P < 0.02, Fisher's exact), suggesting reduced recombination along the non-disjoined chromosomes 21 involved in paternal MI non-disjunction. No difference in recombination was detected among 27 paternal MII cases as compared with controls. However, cases exhibited a slight increase in the frequency of proximal and medial exchange when compared with controls (0.37 versus 0.28, respectively). Lastly, this study confirmed previous reports of excess male probands among paternally derived trisomy 21 cases. However, we report evidence suggesting an MII stage-specific sex ratio disturbance where 2.5 male probands were found for each female proband. Classification of MII cases based on the position of the exchange event suggested that the proband sex ratio disturbance was restricted to non-telomeric exchange cases. Based on these findings, we propose new models to explain the association between paternally derived trisomy 21 and excessive male probands.

  9. Decreased breast cancer risk in systemic lupus erythematosus: the search for a genetic basis continues.

    PubMed

    Bernatsky, S; Easton, D F; Dunning, A; Michailidou, K; Ramsey-Goldman, R; Gordon, C; Clarke, A E; Foulkes, W

    2012-07-01

    Recent work has demonstrated an important decrease in breast cancers for women with systemic lupus erythematosus (SLE). The reason behind this phenomenon is unknown. Our purpose was to explore whether the single nucleotide polymorphisms (SNPs) predisposing to SLE might be protective against breast cancer (in women in the general population). We focused on loci relevant to 10 SNPs associated with SLE (with a p value of <10(-9)). We determined whether we could establish a decreased frequency of these SNPs in breast cancer cases versus controls, within the general population. To do this we used a large breast cancer genome-wide association study (GWAS) dataset, involving 3,659 breast cancer cases and 4,897 controls. These subjects were all primarily of European ancestry. The population-based GWAS breast cancer data we examined suggested little evidence for important associations between breast cancer and SLE-related SNPs. Within the general population GWAS data, a cytosine(C) nucleotide substitution at rs9888739 (on chromosome 16p11.2) showed a very weak inverse association with breast cancer. The odds ratio (OR) for the rs9888739-C allele was 0.907551 (p value 0.049899) in the GWAS breast cancer sample, compared to controls. There was a slightly stronger, positive, association with breast cancer for rs6445975-G (Guanine) on chromosome 3p14.3, with a breast cancer OR of 1.0911 (p value 0.0097). Within this large breast cancer dataset, we did not demonstrate important associations with 10 lupus-associated SNPs. If decreased breast cancer risk in SLE is influenced by genetic profiles, this may be due to complex interactions and/or epigenetic factors.

  10. IκBα polymorphisms were associated with increased risk of gastric cancer in a southern Chinese population: a case-control study.

    PubMed

    Wang, Shiyan; Zhang, Mingdong; Zeng, Zhirong; Tian, Linwei; Wu, Kaichun; Chu, Jianhong; Fan, Daiming; Hu, Pinjin; Sung, Joseph J Y; Yu, Jun

    2011-04-25

    Nuclear factor-kappa B inhibitor alpha (IκBα) polymorphisms were found to be associated with inflammatory diseases. However, the association between IκBα polymorphisms with gastric cancer is still unknown. We aim to investigate the association between IκBα polymorphisms and gastric cancer risk in a large population-based case-control study among southern Chinese. A population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 1010 gastric cancer patients and 1500 healthy controls were enrolled in this study. IκBα polymorphisms were identified by sequencing of IκBα gene ranging from the 2kb promoter region to the 3.5kb genomic region. Polymorphisms in IκBα were analyzed by TaqMan SNP genotyping assay. rs17103265 deletion homozygote (-/-) had significantly increased gastric cancer risk (OR=2.11, 95% CI=1.17-3.83, P=0.01), compared with rs17103265 T homozygote (TT). rs17103265 (-/-) genotype was significantly associated with increased risk of intestinal-type gastric cancer with (OR=2.21, 95% CI=1.19-4.08, P=0.01), but not with the diffuse or mix type of gastric cancer. rs17103265 (-/-) was associated with poorly differentiated gastric cancer (OR=2.05, 95% CI=1.07-3.94, P=0.03), but not with moderately or well differentiated gastric cancer. A significant decrease in luciferase activity was observed in rs17103265 deletion allele as compared with the vector containing the rs17103265 T allele (P<0.0001). rs17103265 polymorphism was not associated with the prognosis of gastric cancer patients. IκBα rs17103265 deletion homozygote is a novel genetic risk factor for gastric carcinogenesis, especially for the development of certain subtypes of gastric cancer in southern Chinese population. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. A population-based case-control study of cancer of the bile ducts and gallbladder in Quebec, Canada.

    PubMed

    Ghadirian, P; Simard, A; Baillargeon, J

    1993-01-01

    In a population-based case-control study of pancreatic cancer in Greater Montreal between 1984 and 1988, a total of 24 patients with cancer of the bile ducts and 33 patients suffering from cancer of the gallbladder were compared to 239 population-based controls. This study was part of the SEARCH program of the International Agency for Research on Cancer. In cases of cancer of the bile ducts, smoking nonfiltered cigarettes produced a relative risk of 2.82 and a 95% confidence interval of 1.01-7.86 after adjustment for age, sex, other smoking habits, alcohol consumption, schooling, and respondent status. Laxative intake was associated with a risk of 2.87 (1.00-8.22). Coffee drinkers were collectively at lower risk than non-drinkers: OR = 0.26 (0.07-0.95). In patients with cancer of the gallbladder, constipation was related to a risk of 3.19 (1.02-9.95) after adjustment for the same factors. In cases with previous gallbladder problems, the risk was found to be significant [OR = 7.96 (2.03-31.2)], 8 times greater in cases than in controls.

  12. Perinatal factors and the risk of bipolar disorder in Finland.

    PubMed

    Chudal, Roshan; Sourander, Andre; Polo-Kantola, Päivi; Hinkka-Yli-Salomäki, Susanna; Lehti, Venla; Sucksdorff, Dan; Gissler, Mika; Brown, Alan S

    2014-02-01

    Complications during the perinatal period have been associated with neurodevelopmental disorders like schizophrenia and autism. However, similar studies on bipolar disorder (BPD) have been limited and the findings are inconsistent. The aim of this study was to examine the association between perinatal risk factors and BPD. This nested case-control study, based on the Finnish Prenatal Study of Bipolar Disorders (FIPS-B), identified 724 cases and 1419 matched controls from population based registers. Conditional logistic regression was used to examine the associations between perinatal factors and BPD adjusting for potential confounding due to maternal age, psychiatric history and educational level, place of birth, number of previous births and maternal smoking during pregnancy. Children delivered by planned cesarean section had a 2.5-fold increased risk of BPD (95% CI: 1.32-4.78, P<0.01). No association was seen between other examined perinatal risk factors and BPD. The limitations of this study include: the restriction in the sample to treated cases of BPD in the population, and usage of hospital based clinical diagnosis for case ascertainment. In addition, in spite of the large sample size, there was low power to detect associations for certain exposures including the lowest birth weight category and pre-term birth. Birth by planned cesarean section was associated with risk of BPD, but most other perinatal risk factors examined in this study were not associated with BPD. Larger studies with greater statistical power to detect less common exposures and studies utilizing prospective biomarker-based exposures are necessary in the future. © 2013 Published by Elsevier B.V.

  13. The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) Study Protocol

    PubMed Central

    Woo, Daniel; Rosand, Jonathan; Kidwell, Chelsea; McCauley, Jacob L.; Osborne, Jennifer; Brown, Mark W.; West, Sandra E.; Rademacher, Eric W.; Waddy, Salina; Roberts, Jamie N.; Koch, Sebastian; Gonzales, Nicole R.; Sung, Gene; Kittner, Steven J.; Birnbaum, Lee; Frankel, Michael; Daniel Testai, Fernando; Hall, Christiana E.; Elkind, Mitchell S. V.; Flaherty, Matthew; Coull, Bruce; Chong, Ji Y.; Warwick, Tanya; Malkoff, Marc; James, Michael L.; Ali, Latisha K.; Worrall, Bradford B.; Jones, Floyd; Watson, Tiffany; Leonard, Anne; Martinez, Rebecca; Sacco, Ralph I; Langefeld, Carl D.

    2013-01-01

    Background and Purpose Epidemiologic studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, age at presentation, and outcomes among non-Hispanic white, black, and Hispanic populations. We report here the design and methods for this large, prospective, multi-center case-control study of ICH. Methods The ERICH study is a multi-center, prospective case-control study of ICH. Cases are identified by hot-pursuit and enrolled using standard phenotype and risk factor information and include neuroimaging and blood sample collection. Controls are centrally identified by random digit dialing to match cases by age (+/−5 years), race, ethnicity, gender and metropolitan region. Results As of March 22, 2013, 1,655 cases of ICH had been recruited into the study which is 101.5% of the target for that date and 851 controls had been recruited which is 67.2% of the target for that date (1,267 controls) for a total of 2,506 subjects which is 86.5% of the target for that date (2,897 subjects). Of the 1,655 cases enrolled, 1,640 cases had the case interview entered into the database of which 628 (38%) were non-Hispanic black, 458 (28%) were non-Hispanic white and 554 (34%) were Hispanic. Of the 1,197 cases with imaging submitted, 876 (73.2%) had a 24 hour follow-up CT available In addition to CT imaging, 607 cases have had MRI evaluation. Conclusion The ERICH study is a large, case-control study of ICH with particular emphasis on recruitment of minority populations for the identification of genetic and epidemiologic risk factors for ICH and outcomes after ICH. PMID:24021679

  14. Association between diabetes mellitus and the occurrence and outcome of intracerebral hemorrhage

    PubMed Central

    Boulanger, Marion; Poon, Michael T.C.; Wild, Sarah H.

    2016-01-01

    Objective: Whether diabetes mellitus (DM) is a risk factor for spontaneous intracerebral hemorrhage (ICH) and influences outcome after ICH remains unclear. Methods: One reviewer searched Ovid MEDLINE and Embase 1980–2014 inclusive for studies investigating the associations between DM and ICH occurrence or DM and ICH case fatality. Two reviewers independently confirmed each study's eligibility, assessed risk of bias, and extracted data. One reviewer combined studies using random effects meta-analysis. Results: Nineteen case-control studies involving 3,397 people with ICH and 5,747 people without ICH found an association between DM and ICH occurrence (unadjusted odds ratio [OR] 1.23, 95% confidence interval [CI] 1.04–1.45; I2 = 22%), which did not differ between 17 hospital-based and 2 population-based studies (pdiff = 0.70), and was similar in the 16 studies that controlled for age and sex (unadjusted OR 1.15, 95% CI 0.95–1.40; I2 = 14%). This association was not identified in 3 population-based cohort studies in which ICH occurred in 38 (0.66%) of 5,724 people with DM and 448 (0.57%) of 78,702 people without DM (unadjusted risk ratio [RR] 1.27, 95% CI 0.68–2.36; I2 = 69%). DM was associated with a higher case fatality by 30 days or hospital discharge in 18 cohort studies involving 813 people with DM and 3,714 people without DM (unadjusted RR 1.52, 95% CI 1.28–1.81; I2 = 49%). Conclusions: The findings suggest that there may be modest associations between DM and ICH occurrence and outcome, but further information from large, population-based studies that account for confounding is required before the association can be confirmed. PMID:27473136

  15. Association between glutathione S-transferase P1 Ile (105) Val gene polymorphism and chronic obstructive pulmonary disease: A meta-analysis based on seventeen case-control studies.

    PubMed

    Yang, Lingjing; Li, Xixia; Tong, Xiang; Fan, Hong

    2015-12-01

    Previous studies have shown that glutathione S-transferase P1 (GSTP1) was associated with chronic obstructive pulmonary disease (COPD). However, the association between GSTP1 Ile (105) Val gene polymorphism and COPD remains controversial. To drive a more precise estimation, we performed a meta-analysis based on published case-control studies. An electronic search of PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated (CNKI) Database for papers on GSTP1 Ile (105) Val gene polymorphism and COPD risk was performed. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygote model, heterozygote model, dominant model, recessive model and an additive mode. Statistical heterogeneity, test of publication bias and sensitivity analysis was performed. The software STATA (Version 13.0) was used data analysis. Overall, seventeen studies with 1892 cases and 2012 controls were included in this meta-analysis. The GSTP1 Ile (105) Val polymorphism showed pooled odds ratios for the homozygote comparison (OR = 1.501, 95%CI [0.862, 2.614]), heterozygote comparison (OR = 0.924, 95%CI [0.733, 1.165]), dominant model (OR = 1.003, 95%CI [0.756, 1.331]), recessive model (OR = 1.510, 95%CI [0.934, 2.439]), and an additive model (OR = 1.072, 95%CI [0.822, 1.398]). In conclusion, the current meta-analysis, based on the most updated information, showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in any genetic models. The results of subgroup analysis also showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in Asian population and Caucasian population. Further studies involving large populations and careful control with age, sex, ethnicity, and cigarette smoking are greatly needed.

  16. Ischemic stroke subtypes: a population-based study of incidence rates among blacks and whites.

    PubMed

    Schneider, Alexander T; Kissela, Brett; Woo, Daniel; Kleindorfer, Dawn; Alwell, Kathleen; Miller, Rosemary; Szaflarski, Jerzy; Gebel, James; Khoury, Jane; Shukla, Rakesh; Moomaw, Charles; Pancioli, Arthur; Jauch, Edward; Broderick, Joseph

    2004-07-01

    Blacks have an excess burden of stroke compared with whites; however, data comparing ischemic stroke subtypes among the 2 groups are limited and typically involve relative frequencies. The objective of this study is to compare the incidence rates of ischemic stroke subtypes between blacks and whites within a large, representative, biracial population. The Greater Cincinnati/Northern Kentucky Stroke Study is designed to measure incidence rates and trends of all strokes within a well-defined, large, biracial population. Hospitalized cases were ascertained by International Classification of Disease (9th revision; ICD-9) discharge codes. Out-of-hospital events were ascertained by prospective screening of emergency department admission logs, review of coroners' cases, and monitoring all public health and hospital-based primary care clinics. A sampling scheme was used to ascertain events from nursing homes and all other primary care physician offices. All potential cases underwent detailed chart abstraction and confirmed by physician review. Based on all available clinical, laboratory, and radiographic information, ischemic stroke cases were subtyped into the following categories: cardioembolic, large-vessel, small-vessel, other, and stroke of undetermined cause. Race-specific incidence rates were calculated and compared after adjusting for age and gender, and standardizing to the 1990 US population. Between July 1, 1993, and June 30, 1994, 1956 first-ever ischemic strokes occurred among blacks and whites in the study population. Small-vessel strokes and strokes of undetermined cause were nearly twice as common among blacks. Large-vessel strokes were 40% more common among blacks than whites, and there was a trend toward cardioembolic strokes being more common among blacks. The excess burden of ischemic strokes among blacks compared with whites is not uniformly spread across the different subtypes. Large-vessel strokes are more common and cardioembolic stroke are as common among blacks, traditionally thought to be more common among whites.

  17. Surveillance of work-related asthma in new york state.

    PubMed

    Tice, Cori J; Cummings, Karen R; Gelberg, Kitty H

    2010-04-01

    The objective of this paper is to determine the percent of adults with asthma attributable to work and describe characteristics of the work-related asthma population in New York State. Sociodemographic and control characteristics of those with and without work-related asthma are compared. Data from three population-based surveys and one case-based surveillance system were analyzed. Work-relatedness of asthma was determined by self-report for the population-based surveys and by physician report for the case-based system. Self-reported sociodemographic and control characteristics were analyzed for the population-based surveys by work-relatedness. The percent of work-relatedness among adults with current asthma in New York State ranged from 10.6% to 44.5%. Significantly more adults with work-related asthma had poorly controlled asthma than those without work-related asthma. More adults with work-related asthma also tended to be employed in the manufacturing, educational services, and public administration industries than the general population. The most frequently reported exposure was dust. Adults with work-related asthma have decreased control and adverse socioeconomic impacts compared to those with asthma that is not work-related. Increased recognition and physician reporting is necessary to further prevent the impact of work-related exposures.

  18. Prevalence of Periodontitis in Patients with Established Rheumatoid Arthritis: A Swedish Population Based Case-Control Study

    PubMed Central

    Eriksson, Kaja; Nise, Lena; Kats, Anna; Luttropp, Elin; Catrina, Anca Irinel; Askling, Johan; Jansson, Leif; Alfredsson, Lars; Klareskog, Lars; Lundberg, Karin; Yucel-Lindberg, Tülay

    2016-01-01

    Introduction The possible hypothesis of a link between periodontitis and rheumatoid arthritis (RA), specifically anti-citrullinated protein antibody (ACPA) positive RA, prompted us to investigate the prevalence of periodontitis in the Swedish Epidemiological Investigation of RA (EIRA), a well-characterised population-based RA case-control cohort. Methods Periodontal status of 2,740 RA cases and 3,942 matched controls was retrieved through linking EIRA with the National Dental Health Registry (DHR), where dental diagnostic- and treatment codes on the adult Swedish population have been registered. Dental records from 100 cases and controls were reviewed to validate the periodontal diagnostic codes in DHR. Results The reviewed dental records confirmed 90% of the periodontitis diagnoses in DHR among RA cases, and 88% among controls. We found the positive predictive value of periodontitis diagnoses in the DHR to be 89% (95% CI 78 to 95%) with a sensitivity of 77% (95% CI: 65 to 86%). In total, 86% of EIRA participants were identified in DHR. The risk for periodontitis increased by age and current smoking status in both cases as well as controls. No significant differences in prevalence of periodontal disease in terms of gingivitis, periodontitis, peri-implantitis or increased risk for periodontitis or peri-implantitis were observed between RA cases and controls. In addition, there was no difference on the basis of seropositivity, ACPA or rheumatoid factor (RF), among patients with RA. Conclusions Our data verify that smoking and ageing are risk factors for periodontitis, both in RA and controls. We found no evidence of an increased prevalence of periodontitis in patients with established RA compared to healthy controls, and no differences based on ACPA or RF status among RA subjects. PMID:27203435

  19. Breed-specific incidence rates of canine primary bone tumors — A population based survey of dogs in Norway

    PubMed Central

    Anfinsen, Kristin P.; Grotmol, Tom; Bruland, Oyvind S.; Jonasdottir, Thora J.

    2011-01-01

    This is one of few published population-based studies describing breed specific rates of canine primary bone tumors. Incidence rates related to dog breeds could help clarify the impact of etiological factors such as birth weight, growth rate, and adult body weight/height on development of these tumors. The study population consisted of dogs within 4 large/giant breeds; Irish wolfhound (IW), Leonberger (LB), Newfoundland (NF), and Labrador retriever (LR), born between January 1st 1989 and December 31st 1998. Questionnaires distributed to owners of randomly selected dogs — fulfilling the criteria of breed, year of birth, and registration in the Norwegian Kennel Club — constituted the basis for this retrospective, population-based survey. Of the 3748 questionnaires received by owners, 1915 were completed, giving a response rate of 51%. Forty-three dogs had been diagnosed with primary bone tumors, based upon clinical examination and x-rays. The breeds IW and LB, with 126 and 72 cases per 10 000 dog years at risk (DYAR), respectively, had significantly higher incidence rates of primary bone tumors than NF and LR (P < 0.0001). Incidence rates for the latter were 11 and 2 cases per 10 000 DYAR, respectively. Pursuing a search for risk factors other than body size/weight is supported by the significantly different risks of developing primary bone tumors between similarly statured dogs, like NF and LB, observed in this study. Defining these breed-specific incidence rates enables subsequent case control studies, ultimately aiming to identify specific etiological factors for developing primary bone tumors. PMID:22210997

  20. A Model Framework to Estimate Impact and Cost of Genetics-Based Sterile Insect Methods for Dengue Vector Control

    PubMed Central

    Alphey, Nina; Alphey, Luke; Bonsall, Michael B.

    2011-01-01

    Vector-borne diseases impose enormous health and economic burdens and additional methods to control vector populations are clearly needed. The Sterile Insect Technique (SIT) has been successful against agricultural pests, but is not in large-scale use for suppressing or eliminating mosquito populations. Genetic RIDL technology (Release of Insects carrying a Dominant Lethal) is a proposed modification that involves releasing insects that are homozygous for a repressible dominant lethal genetic construct rather than being sterilized by irradiation, and could potentially overcome some technical difficulties with the conventional SIT technology. Using the arboviral disease dengue as an example, we combine vector population dynamics and epidemiological models to explore the effect of a program of RIDL releases on disease transmission. We use these to derive a preliminary estimate of the potential cost-effectiveness of vector control by applying estimates of the costs of SIT. We predict that this genetic control strategy could eliminate dengue rapidly from a human community, and at lower expense (approximately US$ 2∼30 per case averted) than the direct and indirect costs of disease (mean US$ 86–190 per case of dengue). The theoretical framework has wider potential use; by appropriately adapting or replacing each component of the framework (entomological, epidemiological, vector control bio-economics and health economics), it could be applied to other vector-borne diseases or vector control strategies and extended to include other health interventions. PMID:21998654

  1. Primary aldosteronism and thyroid disorders in atrial fibrillation: A Swedish nationwide case-control study.

    PubMed

    Mourtzinis, Georgios; Adamsson Eryd, Samuel; Rosengren, Annika; Björck, Lena; Adiels, Martin; Johannsson, Gudmundur; Manhem, Karin

    2018-05-01

    Background Atrial fibrillation is associated with hyperthyroidism. Patients with primary aldosteronism have an increased prevalence of atrial fibrillation. However, the prevalence of primary aldosteronism in the atrial fibrillation population is unknown. Aim This nationwide case-control study aimed to compare the prevalence of primary aldosteronism and thyroid disorders in patients with atrial fibrillation with that of age- and sex-matched controls. Methods We identified all atrial fibrillation cases in Sweden between 1987 and 2013 ( n = 713,569) by using the Swedish National Patient Register. A control cohort without atrial fibrillation was randomly selected from the Swedish Total Population Register with a case to control ratio of 1:2. This control cohort was matched for age, sex and place of birth ( n = 1,393,953). Results The prevalence of primary aldosteronism in December 2013 was 0.056% in the atrial fibrillation cohort and 0.024% in controls. At the same time, the prevalence of hypothyroidism was 5.9% in the atrial fibrillation cohort and 3.7% in controls. The prevalence of hyperthyroidism was 2.3% in the atrial fibrillation cohort and 0.8% in controls. Conclusion This study shows, for the first time, a doubled prevalence of primary aldosteronism in a large cohort of patients with atrial fibrillation compared with the general population. There is also an increased prevalence of hypo- and hyper-thyroidism in patients with atrial fibrillation compared with the general population.

  2. Antioxidants and breast cancer risk- a population-based case-control study in Canada

    PubMed Central

    2011-01-01

    Background The effect of antioxidants on breast cancer is still controversial. Our objective was to assess the association between antioxidants and breast cancer risk in a large population-based case-control study. Methods The study population included 2,362 cases with pathologically confirmed incident breast cancer (866 premenopausal and 1,496 postmenopausal) and 2,462 controls in Canada. Intakes of antioxidants from diet and from supplementation as well as other potential risk factors for breast cancer were collected by a self-reported questionnaire. Results Compared with subjects with no supplementation, 10 years or longer supplementation of zinc had multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) of 0.46 (0.25-0.85) for premenopausal women, while supplementation of 10 years or longer of multiple vitamin, beta-carotene, vitamin C, vitamin E and zinc had multivariable-adjusted ORs (95% CIs) of 0.74 (0.59, 0.92), 0.58 (0.36, 0.95), 0.79 (0.63-0.99), 0.75 (0.58, 0.97), and 0.47 (0.28-0.78), respectively, for postmenopausal women. No significant effect of antioxidants from dietary sources (including beta-carotene, alpha-carotene, lycopene, lutein and zeaxanthin, vitamin C, vitamin E, selenium and zinc) or from supplementation less than 10 years was observed. Conclusions This study suggests that supplementation of zinc in premenopausal women, and supplementation of multiple vitamin, beta-carotene, vitamin C, vitamin E and zinc in postmenopausal women for 10 or more years may protect women from developing breast cancer. However, we were unable to determine the overall effect of total dose or intake from both diet and supplement. PMID:21864361

  3. α1-Antitrypsin Protease Inhibitor MZ Heterozygosity Is Associated With Airflow Obstruction in Two Large Cohorts

    PubMed Central

    Sørheim, Inga-Cecilie; Bakke, Per; Gulsvik, Amund; Pillai, Sreekumar G.; Johannessen, Ane; Gaarder, Per I.; Campbell, Edward J.; Agustí, Alvar; Calverley, Peter M. A.; Donner, Claudio F.; Make, Barry J.; Rennard, Stephen I.; Vestbo, Jørgen; Wouters, Emiel F. M.; Paré, Peter D.; Levy, Robert D.; Coxson, Harvey O.; Lomas, David A.; Hersh, Craig P.

    2010-01-01

    Background: Severe α1-antitrypsin deficiency is a known genetic risk factor for COPD. Heterozygous (protease inhibitor [PI] MZ) individuals have moderately reduced serum levels of α1-antitrypsin, but whether they have an increased risk of COPD is uncertain. Methods: We compared PI MZ and PI MM individuals in two large populations: a case-control study from Norway (n = 1,669) and a multicenter family-based study from Europe and North America (n = 2,707). We sought to determine whether PI MZ was associated with the specific COPD-related phenotypes of lung function and quantitative CT scan measurements of emphysema and airway disease. Results: PI MZ was associated with a 3.5% lower FEV1/FVC ratio in the case-control study (P = .035) and 3.9% lower FEV1/vital capacity (VC) ratio in the family study (P = .009). In the case-control study, PI MZ also was associated with 3.7% more emphysema on quantitative analysis of chest CT scans (P = .003). The emphysema result was not replicated in the family study. PI MZ was not associated with airway wall thickness or COPD status in either population. Among subjects with low smoking exposure (< 20 pack-years), PI MZ individuals had more severe emphysema on chest CT scan than PI MM individuals in both studies. Conclusions: Compared with PI MM individuals, PI MZ heterozygotes had lower FEV1/(F)VC ratio in two independent studies. Our results suggest that PI MZ individuals may be slightly more susceptible to the development of airflow obstruction than PI MM individuals. PMID:20595457

  4. Candidate genes for COPD in two large data sets.

    PubMed

    Bakke, P S; Zhu, G; Gulsvik, A; Kong, X; Agusti, A G N; Calverley, P M A; Donner, C F; Levy, R D; Make, B J; Paré, P D; Rennard, S I; Vestbo, J; Wouters, E F M; Anderson, W; Lomas, D A; Silverman, E K; Pillai, S G

    2011-02-01

    Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV₁) % predicted and FEV₁/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV₁ % predicted and FEV₁/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.

  5. Lifestyle factors and risk of leukemia and non-Hodgkin's lymphoma: a case-control study.

    PubMed

    Parodi, Stefano; Santi, Irene; Marani, Enza; Casella, Claudia; Puppo, Antonella; Garrone, Elsa; Fontana, Vincenzo; Stagnaro, Emanuele

    2016-03-01

    Risk factors for leukemia and lymphomas in adults are largely unknown. This study was aimed at evaluating the association between lifestyle factors and the risk of hematological malignancies in an adult population. Data were drawn from a population-based case-control study carried out in Italy and included 294 cases (199 lymphoid and 95 myeloid) and 279 controls. Analyses were performed using standard multivariable logistic regression. Hair dye use for at least 15 years was associated with a higher risk of lymphoid malignancies among females (OR 2.3, 95 % CI 1.0-4.9, p = 0.036, test for trend). Furthermore, a protective effect of a moderate to heavy tea consumption on the risk of myeloid malignancies was observed (OR 0.4, 95 % CI 0.2-0.9, p = 0.017). No association was found for the use of alcoholic beverages and tobacco smoking. Our results confirm the potential carcinogenic effect of prolonged hair dye use observed in previous investigations. The excess risk could be explained by exposure to a higher concentration of toxic compounds in hair products used in the past. The protective effect of regular tea consumption observed in an area with a very high prevalence of black tea consumers deserves further investigation.

  6. Correction of Population Stratification in Large Multi-Ethnic Association Studies

    PubMed Central

    Serre, David; Montpetit, Alexandre; Paré, Guillaume; Engert, James C.; Yusuf, Salim; Keavney, Bernard; Hudson, Thomas J.; Anand, Sonia

    2008-01-01

    Background The vast majority of genetic risk factors for complex diseases have, taken individually, a small effect on the end phenotype. Population-based association studies therefore need very large sample sizes to detect significant differences between affected and non-affected individuals. Including thousands of affected individuals in a study requires recruitment in numerous centers, possibly from different geographic regions. Unfortunately such a recruitment strategy is likely to complicate the study design and to generate concerns regarding population stratification. Methodology/Principal Findings We analyzed 9,751 individuals representing three main ethnic groups - Europeans, Arabs and South Asians - that had been enrolled from 154 centers involving 52 countries for a global case/control study of acute myocardial infarction. All individuals were genotyped at 103 candidate genes using 1,536 SNPs selected with a tagging strategy that captures most of the genetic diversity in different populations. We show that relying solely on self-reported ethnicity is not sufficient to exclude population stratification and we present additional methods to identify and correct for stratification. Conclusions/Significance Our results highlight the importance of carefully addressing population stratification and of carefully “cleaning” the sample prior to analyses to obtain stronger signals of association and to avoid spurious results. PMID:18196181

  7. Neurocognitive performance in family-based and case-control studies of schizophrenia.

    PubMed

    Gur, Ruben C; Braff, David L; Calkins, Monica E; Dobie, Dorcas J; Freedman, Robert; Green, Michael F; Greenwood, Tiffany A; Lazzeroni, Laura C; Light, Gregory A; Nuechterlein, Keith H; Olincy, Ann; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Stone, William S; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Gur, Raquel E

    2015-04-01

    Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures. The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS. Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms. Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs.

  8. Allium Vegetables and Stomach Cancer Risk in China

    PubMed Central

    Setiawan, Veronica Wendy; Yu, Guo-Pei; Lu, Qing-Yi; Lu, Ming-Lan; Yu, Shun-Zhang; Mu, Lina; Zhang, Jian-Guo; Kurtz, Robert C; Cai, Lin; Hsieh, Chung-Cheng; Zhang, Zuo-Feng

    2014-01-01

    Although the incidence of stomach cancer has been declining, it remains the second leading cause of cancer death worldwide. Potential protective effects of allium vegetables against cancer have been reported by a few epidemiologic studies in Chinese populations, but the sample sizes of these studies were relatively small. We examined the associations between allium vegetable consumption and stomach cancer in a large population-based case-control study in Shanghai (750 cases and 750 age- and gender-matched controls) and Qingdao (128 cases and 128 age- and gender-matched controls). Epidemiological data were collected by a standard questionnaire, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression in SAS. After adjusting for matching variables, education, body mass index, pack-years of smoking, alcohol drinking, salt intake, and fruit and vegetable intake, inverse relationships with dose response pattern were observed between frequency of onion intake and stomach cancer in Qingdao (P for trend=0.02) and Shanghai (P for trend=0.04) populations. In Shanghai, negative dose-response relationships were observed between monthly intake of onions (P=0.03), monthly intake of garlic stalks (P=0.04) and distal cancer (but not with cardia cancer). Negative association was also noted between intake of garlic stalks (often vs. never) and risk of stomach cancer in Qingdao (OR=0.30; 95% CI: 0.12–0.77). Our results confirm the protective effect of allium vegetables (especially garlic and onions) against stomach cancer. PMID:16236005

  9. Asthma exacerbation and proximity of residence to major roads: a population-based matched case-control study among the pediatric Medicaid population in Detroit, Michigan

    PubMed Central

    2011-01-01

    Background The relationship between asthma and traffic-related pollutants has received considerable attention. The use of individual-level exposure measures, such as residence location or proximity to emission sources, may avoid ecological biases. Method This study focused on the pediatric Medicaid population in Detroit, MI, a high-risk population for asthma-related events. A population-based matched case-control analysis was used to investigate associations between acute asthma outcomes and proximity of residence to major roads, including freeways. Asthma cases were identified as all children who made at least one asthma claim, including inpatient and emergency department visits, during the three-year study period, 2004-06. Individually matched controls were randomly selected from the rest of the Medicaid population on the basis of non-respiratory related illness. We used conditional logistic regression with distance as both categorical and continuous variables, and examined non-linear relationships with distance using polynomial splines. The conditional logistic regression models were then extended by considering multiple asthma states (based on the frequency of acute asthma outcomes) using polychotomous conditional logistic regression. Results Asthma events were associated with proximity to primary roads with an odds ratio of 0.97 (95% CI: 0.94, 0.99) for a 1 km increase in distance using conditional logistic regression, implying that asthma events are less likely as the distance between the residence and a primary road increases. Similar relationships and effect sizes were found using polychotomous conditional logistic regression. Another plausible exposure metric, a reduced form response surface model that represents atmospheric dispersion of pollutants from roads, was not associated under that exposure model. Conclusions There is moderately strong evidence of elevated risk of asthma close to major roads based on the results obtained in this population-based matched case-control study. PMID:21513554

  10. Rarity of the Alzheimer Disease–Protective APP A673T Variant in the United States

    PubMed Central

    Wang, Li-San; Naj, Adam C.; Graham, Robert R.; Crane, Paul K.; Kunkle, Brian W.; Cruchaga, Carlos; Gonzalez Murcia, Josue D.; Cannon-Albright, Lisa; Baldwin, Clinton T.; Zetterberg, Henrik; Blennow, Kaj; Kukull, Walter A.; Faber, Kelley M.; Schupf, Nicole; Norton, Maria C.; Tschanz, JoAnn T.; Munger, Ronald G.; Corcoran, Christopher D.; Rogaeva, Ekaterina; Lin, Chiao-Feng; Dombroski, Beth A.; Cantwell, Laura B.; Partch, Amanda; Valladares, Otto; Hakonarson, Hakon; St George-Hyslop, Peter; Green, Robert C.; Goate, Alison M.; Foroud, Tatiana M.; Carney, Regina M.; Larson, Eric B.; Behrens, Timothy W.; Kauwe, John S. K.; Haines, Jonathan L.; Farrer, Lindsay A.; Pericak-Vance, Margaret A.; Mayeux, Richard; Schellenberg, Gerard D.

    2015-01-01

    IMPORTANCE Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States. OBJECTIVE To determine the frequency of the APP A673T variant in a large group of elderly cognitively normal controls and AD cases from the United States and in 2 case-control cohorts from Sweden. DESIGN, SETTING, AND PARTICIPANTS Case-control association analysis of variant APP A673T in US and Swedish white individuals comparing AD cases with cognitively intact elderly controls. Participants were ascertained at multiple university-associated medical centers and clinics across the United States and Sweden by study-specific sampling methods. They were from case-control studies, community-based prospective cohort studies, and studies that ascertained multiplex families from multiple sources. MAIN OUTCOMES AND MEASURES Genotypes for the APP A673T variant were determined using the Infinium HumanExome V1 Beadchip (Illumina, Inc) and by TaqMan genotyping (Life Technologies). RESULTS The A673T variant genotypes were evaluated in 8943 US AD cases, 10 480 US cognitively normal controls, 862 Swedish AD cases, and 707 Swedish cognitively normal controls. We identified 3 US individuals heterozygous for A673T, including 1 AD case (age at onset, 89 years) and 2 controls (age at last examination, 82 and 77 years). The remaining US samples were homozygous for the alanine (A673) allele. In the Swedish samples, 3 controls were heterozygous for A673T and all AD cases were homozygous for the A673 allele. We also genotyped a US family previously reported to harbor the A673T variant and found a mother-daughter pair, both cognitively normal at ages 72 and 84 years, respectively, who were both heterozygous for A673T; however, all individuals with AD in the family were homozygous for A673. CONCLUSIONS AND RELEVANCE The A673T variant is extremely rare in US cohorts and does not play a substantial role in risk for AD in this population. This variant may be primarily restricted to Icelandic and Scandinavian populations. PMID:25531812

  11. Twenty Years of Active Bacterial Core Surveillance

    PubMed Central

    Schaffner, William; Farley, Monica M.; Lynfield, Ruth; Bennett, Nancy M.; Reingold, Arthur; Thomas, Ann; Harrison, Lee H.; Nichols, Megin; Petit, Susan; Miller, Lisa; Moore, Matthew R.; Schrag, Stephanie J.; Lessa, Fernanda C.; Skoff, Tami H.; MacNeil, Jessica R.; Briere, Elizabeth C.; Weston, Emily J.; Van Beneden, Chris

    2015-01-01

    Active Bacterial Core surveillance (ABCs) was established in 1995 as part of the Centers for Disease Control and Prevention Emerging Infections Program (EIP) network to assess the extent of invasive bacterial infections of public health importance. ABCs is distinctive among surveillance systems because of its large, population-based, geographically diverse catchment area; active laboratory-based identification of cases to ensure complete case capture; detailed collection of epidemiologic information paired with laboratory isolates; infrastructure that allows for more in-depth investigations; and sustained commitment of public health, academic, and clinical partners to maintain the system. ABCs has directly affected public health policies and practices through the development and evaluation of vaccines and other prevention strategies, the monitoring of antimicrobial drug resistance, and the response to public health emergencies and other emerging infections. PMID:26292067

  12. Occupational exposure to diesel and gasoline emissions and lung cancer in Canadian men.

    PubMed

    Villeneuve, Paul J; Parent, Marie-Élise; Sahni, Vanita; Johnson, Kenneth C

    2011-07-01

    The International Agency for Research on Cancer classifies diesel exhaust as a probable human carcinogen; this decision is based largely from lung cancer evidence. Gasoline exhaust is classified as a possible carcinogen. Epidemiological studies are needed that improve upon some of the limitations of previous research with respect to the characterization of exposure, and the control for the potential confounding influence of smoking and other occupational exposures. Our objective was to investigate associations between occupational exposure to diesel and gasoline engine emissions and lung cancer. We used a case-control study design that involved men 40 years of age and older at the time of interview. Analyses are based on 1681 incident cases of lung cancer and 2,053 population controls. A self-reported questionnaire elicited a lifetime occupational history, including general tasks, and information on other potential risk factors. Occupational exposures to diesel and gasoline emissions, crystalline silica, and asbestos were assigned to each job held by study subjects by industrial hygienists who were blind to case-control status. Exposure metrics for diesel and gasoline emissions that were modeled included: ever exposure, cumulative exposure, and concentration of exposure. We found a dose-response relationship between cumulative occupational exposure to diesel engine emissions and lung cancer. This association was more pronounced for the squamous and large cell subtypes with adjusted odds ratios across the three increasing tertiles of cumulative lifetime exposure relative to those with no exposure of 0.99, 1.25, and 1.32 (p=0.04) for squamous cell carcinoma, and 1.06, 1.19, 1.68 (p=0.02) for large cell carcinoma. While the association with cumulative exposure to gasoline was weakly positive, it was not statistically significant. Our findings suggest that exposure to diesel engine emissions increases the risk of lung cancer particularly for squamous and large cell carcinoma subtypes. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

  13. How allele frequency and study design affect association test statistics with misrepresentation errors.

    PubMed

    Escott-Price, Valentina; Ghodsi, Mansoureh; Schmidt, Karl Michael

    2014-04-01

    We evaluate the effect of genotyping errors on the type-I error of a general association test based on genotypes, showing that, in the presence of errors in the case and control samples, the test statistic asymptotically follows a scaled non-central $\\chi ^2$ distribution. We give explicit formulae for the scaling factor and non-centrality parameter for the symmetric allele-based genotyping error model and for additive and recessive disease models. They show how genotyping errors can lead to a significantly higher false-positive rate, growing with sample size, compared with the nominal significance levels. The strength of this effect depends very strongly on the population distribution of the genotype, with a pronounced effect in the case of rare alleles, and a great robustness against error in the case of large minor allele frequency. We also show how these results can be used to correct $p$-values.

  14. Oral contraceptive use, parity, and constitutional characteristics in soft tissue sarcoma: a Swedish population-based case-control study 1988-2009.

    PubMed

    Wagner, Philippe; Alvegård, Thor; Ranstam, Jonas; Rydholm, Anders; Vult von Steyern, Fredrik; Olsson, Håkan

    2014-09-01

    The study was designed to investigate the influence of surrogate factors associated with sex (SH) and growth hormones (GH) on the risk of developing soft tissue sarcomas (STS). The etiology of soft tissue sarcoma is largely unknown. We have studied the effect of hormone related factors on STS in the Swedish population between 1988 and 2009 using a population-based matched case-control design. Our study is the largest on this topic to date, including 634 cases in a primary matched analysis and 855 cases in an unmatched sensitivity analysis. We identified protective effects connected to constitutional characteristics, hormonal and reproductive factors. Being shorter than your peers at age 11 was associated with an odds ratio (OR) of 0.51 (0.36-0.74). Having used oral contraceptives (OC), OR 0.75 (0.49-1.15), and high parity, OR 0.16 (0.04-0.63), comparing three or more children to two or less, also appeared to reduce the risk of STS. The risk was further reduced with the duration of OC use (p = 0.01), comparing use for 11 years or more to use for 3 years or less yielded an OR of 0.10 (0.02-0.41). No effect was observed for ever having had perimenopausal hormone therapy OR 1.02 (0.70-1.47). The effect of BMI varied significantly with subtype (p = 0.03) and tumor location (p < 0.001). We observed surrogates of SH, GH, and insulin-like growth factor 1 to be associated with STS development. These findings are important as they may connect STSs to the group of hormone-dependent tumors, potentially revealing common treatment and prevention targets.

  15. Patterns of cannabis use in patients with Inflammatory Bowel Disease: A population based analysis.

    PubMed

    Weiss, Alexandra; Friedenberg, Frank

    2015-11-01

    Tobacco use patterns and effects in patients with Inflammatory Bowel Disease have been extensively studied, however the role and patterns of cannabis use remains poorly defined. Our aim was to evaluate patterns of marijuana use in a large population based survey. Cases were identified from the NHANES database from the National Center for Health Statistics for the time period from January, 2009 through December, 2010 as having ulcerative colitis or Crohn's disease, and exact matched with controls using the Propensity Score Module of SPSS, based on age, gender, and sample weighted using the nearest neighbor method. After weighting, 2084,895 subjects with IBD and 2013,901 control subjects were identified with no significant differences in demographic characteristics. Subjects with IBD had a higher incidence of ever having used marijuana/hashish (M/H) (67.3% vs. 60.0%) and an earlier age of onset of M/H use (15.7 years vs. 19.6 years). Patients with IBD were less likely to have used M/H every month for a year, but more likely to use a heavier amount per day (64.9% subjects with IBD used three or more joints per day vs. 80.5% of subjects without IBD used two or fewer joints per day). In multivariable logistic regression, presence of IBD, male gender, and age over 40 years predicted M/H use. Our study is the first to evaluate marijuana patterns in a large-scale population based survey. Older, male IBD patients have the highest odds of marijuana use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Validation of a Screening Risk Index for Serious Prescription Opioid-Induced Respiratory Depression or Overdose in a US Commercial Health Plan Claims Database

    PubMed Central

    Zedler, Barbara K; Saunders, William B; Joyce, Andrew R; Vick, Catherine C; Murrelle, E Lenn

    2018-01-01

    Abstract Objective To validate a risk index that estimates the likelihood of overdose or serious opioid-induced respiratory depression (OIRD) among medical users of prescription opioids. Subjects and Methods A case-control analysis of 18,365,497 patients with an opioid prescription from 2009 to 2013 in the IMS PharMetrics Plus commercially insured health plan claims database (CIP). An OIRD event occurred in 7,234 cases. Four controls were selected per case. Validity of the Risk Index for Overdose or Serious Opioid-induced Respiratory Depression (RIOSORD), developed previously using Veterans Health Administration (VHA) patient data, was assessed. Multivariable logistic regression was used within the CIP study population to develop a slightly refined RIOSORD. The composition and performance of the CIP-based RIOSORD was evaluated and compared with VHA-based RIOSORD. Results VHA-RIOSORD performed well in discriminating OIRD events in CIP (C-statistic = 0.85). Additionally, re-estimation of logistic model coefficients in CIP yielded a 0.90 C-statistic. The resulting comorbidity and pharmacotherapy variables most highly associated with OIRD and retained in the CIP-RIOSORD were largely concordant with VHA-RIOSORD. These variables included neuropsychiatric and cardiopulmonary disorders, impaired drug excretion, opioid characteristics, and concurrent psychoactive medications. The average predicted probability of OIRD ranged from 2% to 83%, with excellent agreement between predicted and observed incidence across risk classes. Conclusions RIOSORD had excellent predictive accuracy in a large population of US medical users of prescription opioids, similar to its performance in VHA. This practical risk index is designed to support clinical decision-making for safer opioid prescribing, and its clinical utility should be evaluated prospectively. PMID:28340046

  17. Mapping a New Spontaneous Preterm Birth Susceptibility Gene, IGF1R, Using Linkage, Haplotype Sharing, and Association Analysis

    PubMed Central

    Luukkonen, Aino; Teramo, Kari; Puttonen, Hilkka; Ojaniemi, Marja; Varilo, Teppo; Chaudhari, Bimal P.; Plunkett, Jevon; Murray, Jeffrey C.; McCarroll, Steven A.; Muglia, Louis J.; Palotie, Aarno; Hallman, Mikko

    2011-01-01

    Preterm birth is the major cause of neonatal death and serious morbidity. Most preterm births are due to spontaneous onset of labor without a known cause or effective prevention. Both maternal and fetal genomes influence the predisposition to spontaneous preterm birth (SPTB), but the susceptibility loci remain to be defined. We utilized a combination of unique population structures, family-based linkage analysis, and subsequent case-control association to identify a susceptibility haplotype for SPTB. Clinically well-characterized SPTB families from northern Finland, a subisolate founded by a relatively small founder population that has subsequently experienced a number of bottlenecks, were selected for the initial discovery sample. Genome-wide linkage analysis using a high-density single-nucleotide polymorphism (SNP) array in seven large northern Finnish non-consanginous families identified a locus on 15q26.3 (HLOD 4.68). This region contains the IGF1R gene, which encodes the type 1 insulin-like growth factor receptor IGF-1R. Haplotype segregation analysis revealed that a 55 kb 12-SNP core segment within the IGF1R gene was shared identical-by-state (IBS) in five families. A follow-up case-control study in an independent sample representing the more general Finnish population showed an association of a 6-SNP IGF1R haplotype with SPTB in the fetuses, providing further evidence for IGF1R as a SPTB predisposition gene (frequency in cases versus controls 0.11 versus 0.05, P = 0.001, odds ratio 2.3). This study demonstrates the identification of a predisposing, low-frequency haplotype in a multifactorial trait using a well-characterized population and a combination of family and case-control designs. Our findings support the identification of the novel susceptibility gene IGF1R for predisposition by the fetal genome to being born preterm. PMID:21304894

  18. Socioeconomic Status and Childhood Cancer Incidence: A Population-Based Multilevel Analysis.

    PubMed

    Kehm, Rebecca D; Spector, Logan G; Poynter, Jenny N; Vock, David M; Osypuk, Theresa L

    2018-05-01

    The etiology of childhood cancers remains largely unknown, especially regarding environmental and behavioral risk factors. Unpacking the association between socioeconomic status (SES) and incidence may offer insight into such etiology. We tested associations between SES and childhood cancer incidence in a population-based case-cohort study (source cohort: Minnesota birth registry, 1989-2014). Cases, ages 0-14 years, were linked from the Minnesota Cancer Surveillance System to birth records through probabilistic record linkage. Controls were 4:1 frequency matched on birth year (2,947 cases and 11,907 controls). We tested associations of individual-level (maternal education) and neighborhood-level (census tract composite index) SES using logistic mixed models. In crude models, maternal education was positively associated with incidence of acute lymphoblastic leukemia (odds ratio (OR) = 1.10, 95% confidence interval (CI): 1.02, 1.19), central nervous system tumors (OR = 1.12, 95% CI: 1.04, 1.21), and neuroblastoma (OR = 1.15, 95% CI: 1.02, 1.30). Adjustment for established risk factors-including race/ethnicity, maternal age, and birth weight-substantially attenuated these positive associations. Similar patterns were observed for neighborhood-level SES. Conversely, higher maternal education was inversely associated with hepatoblastoma incidence (adjusted OR = 0.70, 95% CI: 0.51, 0.98). Overall, beyond the social patterning of established demographic and pregnancy-related exposures, SES is not strongly associated with childhood cancer incidence.

  19. Design and validity of a clinic-based case-control study on the molecular epidemiology of lymphoma

    PubMed Central

    Cerhan, James R; Fredericksen, Zachary S; Wang, Alice H; Habermann, Thomas M; Kay, Neil E; Macon, William R; Cunningham, Julie M; Shanafelt, Tait D; Ansell, Stephen M; Call, Timothy G; Witzig, Thomas E; Slager, Susan L; Liebow, Mark

    2011-01-01

    We present the design features and implementation of a clinic-based case-control study on the molecular epidemiology of lymphoma conducted at the Mayo Clinic (Rochester, Minnesota, USA), and then assess the internal and external validity of the study. Cases were newly diagnosed lymphoma patients from Minnesota, Iowa and Wisconsin seen at Mayo and controls were patients from the same region without lymphoma who had a pre-scheduled general medical examination, frequency matched on age, sex and residence. Overall response rates were 67% for cases and 70% for controls; response rates were lower for cases and controls over age 70 years, cases with more aggressive disease, and controls from the local area, although absolute differences were modest. Cases and controls were well-balanced on age, sex, and residence characteristics. Demographic and disease characteristics of NHL cases were similar to population-based cancer registry data. Control distributions were similar to population-based data on lifestyle factors and minor allele frequencies of over 500 SNPs, although smoking rates were slightly lower. Associations with NHL in the Mayo study for smoking, alcohol use, family history of lymphoma, autoimmune disease, asthma, eczema, body mass index, and single nucleotide polymorphisms in TNF (rs1800629), LTA (rs909253), and IL10 (rs1800896) were at a magnitude consistent with estimates from pooled studies in InterLymph, with history of any allergy the only directly discordant result in the Mayo study. These data suggest that this study should have strong internal and external validity. This framework may be useful to others who are designing a similar study. PMID:21686124

  20. A case control study of senile cataract in a hospital based population.

    PubMed

    Badrinath, S S; Sharma, T; Biswas, J; Srinivas, V

    1996-12-01

    A case-control study (244 cases and 264 controls) was done during 1986-89 on a hospital based population to evaluate the risk factors associated with the etiology of senile cataract. Patient with age between 40-60 years, visual acuity of 6/9 or less, and presence of lenticular opacity of senile origin were included as cases. Age matched individuals with absence of lenticular opacity made up the controls. Multivariate logistic regression analysis revealed that higher systolic BP and number of meals were significantly (P < or = 0.05) associated with presence of senile cataract; whereas higher weight, education and income, and utilization of cooking water had a significant protective effect against senile cataract. The present study helps the clinician to understand the possible risk factors associated with the development of senile cataract and could be helpful in designing a intervention strategy in future.

  1. Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort

    PubMed Central

    Namjou, Bahram; Kothari, Parul H.; Kelly, Jennifer A.; Glenn, Stuart B.; Ojwang, Joshua O.; Adler, Adam; Alarcón-Riquelme, Marta E.; Gallant, Caroline J.; Boackle, Susan A.; Criswell, Lindsey A.; Kimberly, Robert P.; Brown, Elizabeth; Edberg, Jeffrey; Stevens, Anne M.; Jacob, Chaim O.; Tsao, Betty P.; Gilkeson, Gary S.; Kamen, Diane L.; Merrill, Joan T.; Petri, Michelle; Goldman, Rosalind Ramsey; Vila, Luis M.; Anaya, Juan-Manuel; Niewold, Timothy B.; Martin, Javier; Pons-Estel, Bernardo A.; Sabio, Jose M.; Callejas, Jose L.; Vyse, Timothy J.; Bae, Sang-Cheol; Perrino, Fred W.; Freedman, Barry I.; Scofield, R. Hal; Moser, Kathy L.; Gaffney, Patrick M.; James, Judith A.; Langefeld, Carl D.; Kaufman, Kenneth M.; Harley, John B.; Atkinson, John P.

    2011-01-01

    Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors play a role. Rare mutations in the TREX1 gene, the major mammalian 3′-5′ exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurologic condition featuring an inflammatory encephalopathy known as Aicardi-Goutières syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. Methods Forty single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene were evaluated in ∼8370 patients with SLE and ∼7490 control subjects. Stringent quality control procedures were applied and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated. Results The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (MAF >10%) revealed a relatively common risk haplotype in European SLE patients with neurologic manifestations, especially seizures, with a frequency of 58% in lupus cases compared to 45% in normal controls (p=0.0008, OR=1.73, 95% CI=1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant genetic associations. For example, a strong association with anti-nRNP was observed in the European cohort at a coding synonymous variant rs56203834 (p=2.99E-13, OR=5.2, 95% CI=3.18-8.56). Conclusion Our data confirm and expand previous reports and provide additional support for the involvement of TREX1 in lupus pathogenesis. PMID:21270825

  2. Rare, evolutionarily unlikely missense substitutions in CHEK2 contribute to breast cancer susceptibility: results from a breast cancer family registry case-control mutation-screening study.

    PubMed

    Le Calvez-Kelm, Florence; Lesueur, Fabienne; Damiola, Francesca; Vallée, Maxime; Voegele, Catherine; Babikyan, Davit; Durand, Geoffroy; Forey, Nathalie; McKay-Chopin, Sandrine; Robinot, Nivonirina; Nguyen-Dumont, Tù; Thomas, Alun; Byrnes, Graham B; Hopper, John L; Southey, Melissa C; Andrulis, Irene L; John, Esther M; Tavtigian, Sean V

    2011-01-18

    Both protein-truncating variants and some missense substitutions in CHEK2 confer increased risk of breast cancer. However, no large-scale study has used full open reading frame mutation screening to assess the contribution of rare missense substitutions in CHEK2 to breast cancer risk. This absence has been due in part to a lack of validated statistical methods for summarizing risk attributable to large numbers of individually rare missense substitutions. Previously, we adapted an in silico assessment of missense substitutions used for analysis of unclassified missense substitutions in BRCA1 and BRCA2 to the problem of assessing candidate genes using rare missense substitution data observed in case-control mutation-screening studies. The method involves stratifying rare missense substitutions observed in cases and/or controls into a series of grades ordered a priori from least to most likely to be evolutionarily deleterious, followed by a logistic regression test for trends to compare the frequency distributions of the graded missense substitutions in cases versus controls. Here we used this approach to analyze CHEK2 mutation-screening data from a population-based series of 1,303 female breast cancer patients and 1,109 unaffected female controls. We found evidence of risk associated with rare, evolutionarily unlikely CHEK2 missense substitutions. Additional findings were that (1) the risk estimate for the most severe grade of CHEK2 missense substitutions (denoted C65) is approximately equivalent to that of CHEK2 protein-truncating variants; (2) the population attributable fraction and the familial relative risk explained by the pool of rare missense substitutions were similar to those explained by the pool of protein-truncating variants; and (3) post hoc power calculations implied that scaling up case-control mutation screening to examine entire biochemical pathways would require roughly 2,000 cases and controls to achieve acceptable statistical power. This study shows that CHEK2 harbors many rare sequence variants that confer increased risk of breast cancer and that a substantial proportion of these are missense substitutions. The study validates our analytic approach to rare missense substitutions and provides a method to combine data from protein-truncating variants and rare missense substitutions into a one degree of freedom per gene test.

  3. Population versus hospital controls for case-control studies on cancers in Chinese hospitals

    PubMed Central

    2011-01-01

    Background Correct control selection is crucial to the internal validity of case-control studies. Little information exists on differences between population and hospital controls in case-control studies on cancers in Chinese hospital setting. Methods We conducted three parallel case-control studies on leukemia, breast and colorectal cancers in China between 2009 and 2010, using population and hospital controls to separately match 540 incident cases by age, gender and residency at a 1:1 ratio. Demographic and lifestyle factors were measured using a validated questionnaire in face-to-face interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using conditional logistic regression analyses. Results The two control groups had closely similar exposure distributions of 15 out of 16 factors, with the only exception being that hospital controls were less likely to have a BMI ≥ 25 (OR = 0.71, 95% CI: 0.54, 0.93). For exposure of green tea drinking, the adjusted ORs (95% CIs) comparing green tealeaves intake ≥ 1000 grams annually with non-drinkers were 0.51 (0.31, 0.83) and 0.21 (0.27, 0.74) for three cancers combined, 0.06 (0.01, 0.61) and 0.07 (0.01, 0.47) for breast cancer, 0.52 (0.29, 0.94) and 0.45 (0.25, 0.82) for colorectal cancer, 0.65 (0.08, 5.63) and 0.57 (0.07, 4.79) for leukemia using hospital and population controls respectively. Conclusions The study found that hospital controls were comparable with population controls for most demographic characteristics and lifestyle factors measured, but there was a slight difference between the two control groups. Hospital outpatients provide a satisfactory control group in hospital-based case-control study in the Chinese hospital setting. PMID:22171783

  4. Population versus hospital controls for case-control studies on cancers in Chinese hospitals.

    PubMed

    Li, Lin; Zhang, Min; Holman, D'Arcy

    2011-12-15

    Correct control selection is crucial to the internal validity of case-control studies. Little information exists on differences between population and hospital controls in case-control studies on cancers in Chinese hospital setting. We conducted three parallel case-control studies on leukemia, breast and colorectal cancers in China between 2009 and 2010, using population and hospital controls to separately match 540 incident cases by age, gender and residency at a 1:1 ratio. Demographic and lifestyle factors were measured using a validated questionnaire in face-to-face interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using conditional logistic regression analyses. The two control groups had closely similar exposure distributions of 15 out of 16 factors, with the only exception being that hospital controls were less likely to have a BMI ≥ 25 (OR = 0.71, 95% CI: 0.54, 0.93). For exposure of green tea drinking, the adjusted ORs (95% CIs) comparing green tealeaves intake ≥ 1000 grams annually with non-drinkers were 0.51 (0.31, 0.83) and 0.21 (0.27, 0.74) for three cancers combined, 0.06 (0.01, 0.61) and 0.07 (0.01, 0.47) for breast cancer, 0.52 (0.29, 0.94) and 0.45 (0.25, 0.82) for colorectal cancer, 0.65 (0.08, 5.63) and 0.57 (0.07, 4.79) for leukemia using hospital and population controls respectively. The study found that hospital controls were comparable with population controls for most demographic characteristics and lifestyle factors measured, but there was a slight difference between the two control groups. Hospital outpatients provide a satisfactory control group in hospital-based case-control study in the Chinese hospital setting.

  5. Behavioral characteristics of Internet gamblers who trigger corporate responsible gambling interventions.

    PubMed

    Gray, Heather M; LaPlante, Debi A; Shaffer, Howard J

    2012-09-01

    As the worldwide popularity of Internet gambling increases, concerns about the potential for gambling-related harm also increase. This paper reports the results of a study examining actual Internet gambling behavior during 10 years of play. We examined the electronic gambling records of subscribers (N=2,066) who triggered a responsible gaming alert system at a large international online gaming company. We compared these cases with control subscribers (N=2,066) who had the same amount of exposure to the Internet gambling service provider. We used discriminant function analysis to explore what aspects of gambling behavior distinguish cases from controls. Indices of the intensity of gambling activity (e.g., total number of bets made, number of bets per betting day) best distinguished cases from controls, particularly in the case of live-action sports betting. Control group players evidenced behavior similar to the population of players using this service. These results add to our understanding of behavioral markers for disordered Internet gambling and will aid in the development of behavior-based algorithms capable of predicting the presence and/or the onset of disordered Internet gambling. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  6. Occupational exposure to asbestos and risk of cholangiocarcinoma: a population-based case-control study in four Nordic countries.

    PubMed

    Farioli, Andrea; Straif, Kurt; Brandi, Giovanni; Curti, Stefania; Kjaerheim, Kristina; Martinsen, Jan Ivar; Sparen, Pär; Tryggvadottir, Laufey; Weiderpass, Elisabete; Biasco, Guido; Violante, Francesco Saverio; Mattioli, Stefano; Pukkala, Eero

    2018-03-01

    To assess the association between occupational exposure to asbestos and the risk of cholangiocarcinoma (CC). We conducted a case-control study nested in the Nordic Occupational Cancer (NOCCA) cohort. We studied 1458 intrahepatic CC (ICC) and 3972 extrahepatic CC (ECC) cases occurring among subjects born in 1920 or later in Finland, Iceland, Norway and Sweden. Each case was individually matched by birth year, gender and country to five population controls. The cumulative exposure to asbestos (measured in fibres (f)/ml × years) was assessed by applying the NOCCA job-exposure matrix to data on occupations collected during national population censuses (conducted in 1960, 1970, 1980/81 and 1990). Odds ratios (OR) and 95% CI were estimated using conditional logistic regression models adjusted by printing industry work. We observed an increasing risk of ICC with cumulative exposure to asbestos: never exposed, OR 1.0 (reference category); 0.1-4.9 f/mL × years, OR 1.1 (95% CI 0.9 to 1.3); 5.0-9.9 f/mL × years, OR 1.3 (95% CI 0.9 to 2.1); 10.0-14.9 f/mL × years, OR 1.6 (95% CI 1.0 to 2.5); ≥15.0 f/mL × years, OR 1.7 (95% CI 1.1 to 2.6). We did not observe an association between cumulative asbestos exposure and ECC. Our study provides evidence that exposure to asbestos might be a risk factor for ICC. Our findings also suggest that the association between ECC and asbestos is null or weaker than that observed for ICC. Further studies based on large industrial cohorts of asbestos workers and possibly accounting for personal characteristics and clinical history are needed. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Rare coding variants in Phospholipase D3 (PLD3) confer risk for Alzheimer's disease

    PubMed Central

    Cruchaga, Carlos; Benitez, Bruno A.; Cai, Yefei; Guerreiro, Rita; Harari, Oscar; Norton, Joanne; Budde, John; Bertelsen, Sarah; Jeng, Amanda T.; Cooper, Breanna; Skorupa, Tara; Carrell, David; Levitch, Denise; Hsu, Simon; Choi, Jiyoon; Ryten, Mina; Sassi, Celeste; Bras, Jose; Gibbs, Raphael J.; Hernandez, Dena G.; Lupton, Michelle K.; Powell, John; Forabosco, Paola; Ridge, Perry G.; Corcoran, Christopher D.; Tschanz, JoAnn T.; Norton, Maria C.; Munger, Ronald G.; Schmutz, Cameron; Leary, Maegan; Demirci, F. Yesim; Bamne, Mikhil N.; Wang, Xingbin; Lopez, Oscar L.; Ganguli, Mary; Medway, Christopher; Turton, James; Lord, Jenny; Braae, Anne; Barber, Imelda; Brown, Kristelle; Pastor, Pau; Lorenzo-Betancor, Oswaldo; Brkanac, Zoran; Scott, Erick; Topol, Eric; Morgan, Kevin; Rogaeva, Ekaterina; Singleton, Andy; Hardy, John; Kamboh, M. Ilyas; George-Hyslop, Peter St; Cairns, Nigel; Morris, John C.; Kauwe, John S.K.; Goate, Alison M.

    2014-01-01

    Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD)1,2. These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low frequency coding variants with large effects on LOAD risk, we performed whole exome-sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large case-control datasets. A rare variant in PLD3 (phospholipase-D family, member 3, rs145999145; V232M) segregated with disease status in two independent families and doubled risk for AD in seven independent case-control series (V232M meta-analysis; OR= 2.10, CI=1.47-2.99; p= 2.93×10-5, 11,354 cases and controls of European-descent). Gene-based burden analyses in 4,387 cases and controls of European-descent and 302 African American cases and controls, with complete sequence data for PLD3, indicate that several variants in this gene increase risk for AD in both populations (EA: OR= 2.75, CI=2.05-3.68; p=1.44×10-11, AA: OR= 5.48, CI=1.77-16.92; p=1.40×10-3). PLD3 is highly expressed in brain regions vulnerable to AD pathology, including hippocampus and cortex, and is expressed at lower levels in neurons from AD brains compared to control brains (p=8.10×10-10). Over-expression of PLD3 leads to a significant decrease in intracellular APP and extracellular Aβ42 and Aβ40, while knock-down of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a two-fold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may be used to identify rare variants with large effects on risk for disease or other complex traits. PMID:24336208

  8. Updated Global Burden of Cholera in Endemic Countries

    PubMed Central

    Ali, Mohammad; Nelson, Allyson R.; Lopez, Anna Lena; Sack, David A.

    2015-01-01

    Background The global burden of cholera is largely unknown because the majority of cases are not reported. The low reporting can be attributed to limited capacity of epidemiological surveillance and laboratories, as well as social, political, and economic disincentives for reporting. We previously estimated 2.8 million cases and 91,000 deaths annually due to cholera in 51 endemic countries. A major limitation in our previous estimate was that the endemic and non-endemic countries were defined based on the countries’ reported cholera cases. We overcame the limitation with the use of a spatial modelling technique in defining endemic countries, and accordingly updated the estimates of the global burden of cholera. Methods/Principal Findings Countries were classified as cholera endemic, cholera non-endemic, or cholera-free based on whether a spatial regression model predicted an incidence rate over a certain threshold in at least three of five years (2008-2012). The at-risk populations were calculated for each country based on the percent of the country without sustainable access to improved sanitation facilities. Incidence rates from population-based published studies were used to calculate the estimated annual number of cases in endemic countries. The number of annual cholera deaths was calculated using inverse variance-weighted average case-fatality rate (CFRs) from literature-based CFR estimates. We found that approximately 1.3 billion people are at risk for cholera in endemic countries. An estimated 2.86 million cholera cases (uncertainty range: 1.3m-4.0m) occur annually in endemic countries. Among these cases, there are an estimated 95,000 deaths (uncertainty range: 21,000-143,000). Conclusion/Significance The global burden of cholera remains high. Sub-Saharan Africa accounts for the majority of this burden. Our findings can inform programmatic decision-making for cholera control. PMID:26043000

  9. Maternal urinary tract infection and related drug treatments during pregnancy and risk of congenital abnormalities in the offspring.

    PubMed

    Bánhidy, F; Acs, N; Puhó, E H; Czeizel, A E

    2006-12-01

    The association between urinary tract infection (UTI) of pregnant women and preterm birth/low birthweight is known, but the possible association between UTI and congenital abnormalities (CAs) was evaluated rarely. Only one study showed an association with atrial septal defect, thus we decided to check this possible association. The population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA); most maternal UTIs were based on medically recorded data. SETTING The HCCSCA, 1980-1996, contained 22 843 newborns or fetuses with CAs and 38 151 matched controls, i.e. newborn infants without any HCAs. Hungarian informative offspring: live births, stillbirths and prenatally diagnosed malformed fetuses. Case-control pair analysis. Twenty-five CA groups. A total of 1542 (6.75%) mothers in the case group had UTI during entire pregnancy compared with 2188 (5.74%) mothers in the control group (adjusted prevalence odds ratios [POR] with 95% CI: 1.15, 1.06-1.24). We did not find a higher prevalence of UTI during the second and/or third months of pregnancy in total case group (adjusted POR with 95% CI: 1.1, 0.9-1.2) and in any group of CAs including atrial septal defect type II. No evidence for the teratogenic effect of maternal UTI and related drug treatments during early pregnancy.

  10. Association between aircraft, road and railway traffic noise and depression in a large case-control study based on secondary data.

    PubMed

    Seidler, Andreas; Hegewald, Janice; Seidler, Anna Lene; Schubert, Melanie; Wagner, Mandy; Dröge, Patrik; Haufe, Eva; Schmitt, Jochen; Swart, Enno; Zeeb, Hajo

    2017-01-01

    Few studies have examined the relationship between traffic noise and depression providing inconclusive results. This large case-control study is the first to assess and directly compare depression risks by aircraft, road traffic and railway noise. The study population included individuals aged ≥40 years that were insured by three large statutory health insurance funds and were living in the region of Frankfurt international airport. Address-specific exposure to aircraft, road and railway traffic noise in 2005 was estimated. Based on insurance claims and prescription data, 77,295 cases with a new clinical depression diagnosis between 2006 and 2010 were compared with 578,246 control subjects. For road traffic noise, a linear exposure-risk relationship was found with an odds ratio (OR) of 1.17 (95% CI=1.10-1.25) for 24-h continuous sound levels ≥70dB. For aircraft noise, the risk estimates reached a maximum OR of 1.23 (95% CI=1.19-1.28) at 50-55dB and decreased at higher exposure categories. For railway noise, risk estimates peaked at 60-65dB (OR=1.15, 95% CI=1.08-1.22). The highest OR of 1.42 (95% CI=1.33-1.52) was found for a combined exposure to noise above 50dB from all three sources. This study indicates that traffic noise exposure might lead to depression. As a potential explanation for the decreasing risks at high traffic noise levels, vulnerable people might actively cope with noise (e.g. insulate or move away). Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Indoor dampness and molds and development of adult-onset asthma: a population-based incident case-control study.

    PubMed Central

    Jaakkola, Maritta S; Nordman, Henrik; Piipari, Ritva; Uitti, Jukka; Laitinen, Jukka; Karjalainen, Antti; Hahtola, Paula; Jaakkola, Jouni J K

    2002-01-01

    Previous cross-sectional and prevalent case-control studies have suggested increased risk of asthma in adults related to dampness problems and molds in homes. We conducted a population-based incident case-control study to assess the effects of indoor dampness problems and molds at work and at home on development of asthma in adults. We recruited systematically all new cases of asthma during a 2.5-year study period (1997-2000) and randomly selected controls from a source population consisting of adults 21-63 years old living in the Pirkanmaa Hospital district, South Finland. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and the control series of 932 controls, after we excluded 76 (7.5%) controls with a history of asthma. In logistic regression analysis adjusting for confounders, the risk of asthma was related to the presence of visible mold and/or mold odor in the workplace (odds ratio, 1.54; 95% confidence interval, 1.01-2.32) but not to water damage or damp stains alone. We estimated the fraction of asthma attributable to workplace mold exposure to be 35.1% (95% confidence interval, 1.0-56.9%) among the exposed. Present results provide new evidence of the relation between workplace exposure to indoor molds and adult-onset asthma. PMID:12003761

  12. Multiple effects and uncertainties of emission control policies in China: Implications for public health, soil acidification, and global temperature.

    PubMed

    Zhao, Yu; McElroy, Michael B; Xing, Jia; Duan, Lei; Nielsen, Chris P; Lei, Yu; Hao, Jiming

    2011-11-15

    Policies to control emissions of criteria pollutants in China may have conflicting impacts on public health, soil acidification, and climate. Two scenarios for 2020, a base case without anticipated control measures and a more realistic case including such controls, are evaluated to quantify the effects of the policies on emissions and resulting environmental outcomes. Large benefits to public health can be expected from the controls, attributed mainly to reduced emissions of primary PM and gaseous PM precursors, and thus lower ambient concentrations of PM2.5. Approximately 4% of all-cause mortality in the country can be avoided (95% confidence interval: 1-7%), particularly in eastern and north-central China, regions with large population densities and high levels of PM2.5. Surface ozone levels, however, are estimated to increase in parts of those regions, despite NOX reductions. This implies VOC-limited conditions. Even with significant reduction of SO2 and NOX emissions, the controls will not significantly mitigate risks of soil acidification, judged by the exceedance levels of critical load (CL). This is due to the decrease in primary PM emissions, with the consequent reduction in deposition of alkaline base cations. Compared to 2005, even larger CL exceedances are found for both scenarios in 2020, implying that PM control may negate any recovery from soil acidification due to SO2 reductions. Noting large uncertainties, current polices to control emissions of criteria pollutants in China will not reduce climate warming, since controlling SO2 emissions also reduces reflective secondary aerosols. Black carbon emission is an important source of uncertainty concerning the effects of Chinese control policies on global temperature change. Given these conflicts, greater consideration should be paid to reconciling varied environmental objectives, and emission control strategies should target not only criteria pollutants but also species such as VOCs and CO2. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Maternal Consumption of Coffee and Caffeine-containing Beverages and Oral Clefts: A Population-based Case-Control Study in Norway

    PubMed Central

    Wilcox, Allen J.; Lie, Rolv T.; Andersen, Lene F.; Drevon, Christian A.

    2009-01-01

    A large, population-based case-control study of facial clefts was carried out in Norway between 1996 and 2001. The study included 573 cases—377 with cleft lip with or without cleft palate and 196 with cleft palate only—and 763 randomly selected controls. Maternal consumption of coffee and other caffeine-containing beverages in early pregnancy was recorded shortly after birth. Compared with that for no coffee consumption, the adjusted odds ratios for cleft lip with or without cleft palate were 1.39 (95% confidence interval: 1.01, 1.92) for less than 3 cups a day and 1.59 (95% confidence interval: 1.05, 2.39) for 3 cups or more. Coffee consumption was not associated with risk of cleft palate only (for ≥3 cups vs. none, adjusted odds ratio = 0.96, 95% confidence interval: 0.55, 1.67). Tea consumption was associated with a reduced odds ratio of both cleft lip with or without cleft palate and cleft palate only. There was little evidence of an association between caffeine exposure and clefts when all sources of caffeine were considered. Adjustment for known confounding factors in general had minor effects on risk estimates. Still, the authors could not rule out the possibility of uncontrolled confounding by factors associated with the habit of drinking coffee. PMID:19342400

  14. Socioeconomic and Nutritional Factors Account for the Association of Gastric Cancer with Amerindian Ancestry in a Latin American Admixed Population

    PubMed Central

    Pereira, Latife; Zamudio, Roxana; Soares-Souza, Giordano; Herrera, Phabiola; Cabrera, Lilia; Hooper, Catherine C.; Cok, Jaime; Combe, Juan M.; Vargas, Gloria; Prado, William A.; Schneider, Silvana; Kehdy, Fernanda; Rodrigues, Maira R.; Chanock, Stephen J.; Berg, Douglas E.; Gilman, Robert H.; Tarazona-Santos, Eduardo

    2012-01-01

    Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers. Although the urban population from Lima is usually considered as mestizo (i.e., admixed from Africans, Europeans, and Native Americans), we observed a high fraction of Native American ancestry (78.4% for the cases and 74.6% for the controls) and a very low African ancestry (<5%). We determined that higher Native American individual ancestry is associated with gastric cancer, but socioeconomic factors associated both with gastric cancer and Native American ethnicity account for this association. Therefore, the high incidence of gastric cancer in Peru does not seem to be related to susceptibility alleles common in this population. Instead, our result suggests a predominant role for ethnic-associated socioeconomic factors and disparities in access to health services. Since Native Americans are a neglected group in genomic studies, we suggest that the population from Lima and other large cities from Western South America with high Native American ancestry background may be convenient targets for epidemiological studies focused on this ethnic group. PMID:22870209

  15. Algorithm development and the clinical and economic burden of Cushing's disease in a large US health plan database.

    PubMed

    Burton, Tanya; Le Nestour, Elisabeth; Neary, Maureen; Ludlam, William H

    2016-04-01

    This study aimed to develop an algorithm to identify patients with CD, and quantify the clinical and economic burden that patients with CD face compared to CD-free controls. A retrospective cohort study of CD patients was conducted in a large US commercial health plan database between 1/1/2007 and 12/31/2011. A control group with no evidence of CD during the same time was matched 1:3 based on demographics. Comorbidity rates were compared using Poisson and health care costs were compared using robust variance estimation. A case-finding algorithm identified 877 CD patients, who were matched to 2631 CD-free controls. The age and sex distribution of the selected population matched the known epidemiology of CD. CD patients were found to have comorbidity rates that were two to five times higher and health care costs that were four to seven times higher than CD-free controls. An algorithm based on eight pituitary conditions and procedures appeared to identify CD patients in a claims database without a unique diagnosis code. Young CD patients had high rates of comorbidities that are more commonly observed in an older population (e.g., diabetes, hypertension, and cardiovascular disease). Observed health care costs were also high for CD patients compared to CD-free controls, but may have been even higher if the sample had included healthier controls with no health care use as well. Earlier diagnosis, improved surgery success rates, and better treatments may all help to reduce the chronic comorbidity and high health care costs associated with CD.

  16. Measuring local depletion of terrestrial game vertebrates by central-place hunters in rural Amazonia.

    PubMed

    Abrahams, Mark I; Peres, Carlos A; Costa, Hugo C M

    2017-01-01

    The degree to which terrestrial vertebrate populations are depleted in tropical forests occupied by human communities has been the subject of an intense polarising debate that has important conservation implications. Conservation ecologists and practitioners are divided over the extent to which community-based subsistence offtake is compatible with ecologically functional populations of tropical forest game species. To quantify depletion envelopes of forest vertebrates around human communities, we deployed a total of 383 camera trap stations and 78 quantitative interviews to survey the peri-community areas controlled by 60 semi-subsistence communities over a combined area of over 3.2 million hectares in the Médio Juruá and Uatumã regions of Central-Western Brazilian Amazonia. Our results largely conform with prior evidence that hunting large-bodied vertebrates reduces wildlife populations near settlements, such that they are only found at a distance to settlements where they are hunted less frequently. Camera trap data suggest that a select few harvest-sensitive species, including lowland tapir, are either repelled or depleted by human communities. Nocturnal and cathemeral species were detected relatively more frequently in disturbed areas close to communities, but individual species did not necessarily shift their activity patterns. Group biomass of all species was depressed in the wider neighbourhood of urban areas rather than communities. Interview data suggest that species traits, especially group size and body mass, mediate these relationships. Large-bodied, large-group-living species are detected farther from communities as reported by experienced informants. Long-established communities in our study regions have not "emptied" the surrounding forest. Low human population density and low hunting offtake due to abundant sources of alternative aquatic protein, suggest that these communities represent a best-case scenario for sustainable hunting of wildlife for food, thereby providing a conservative assessment of game depletion. Given this 'best-case' camera trap and interview-based evidence for hunting depletion, regions with higher human population densities, external trade in wildlife and limited access to alternative protein will likely exhibit more severe depletion.

  17. The Value of Large-Scale Randomised Control Trials in System-Wide Improvement: The Case of the Reading Catch-Up Programme

    ERIC Educational Resources Information Center

    Fleisch, Brahm; Taylor, Stephen; Schöer, Volker; Mabogoane, Thabo

    2017-01-01

    This article illustrates the value of large-scale impact evaluations with counterfactual components. It begins by exploring the limitations of small-scale impact studies, which do not allow reliable inference to a wider population or which do not use valid comparison groups. The paper then describes the design features of a recent large-scale…

  18. Congenital Abnormalities and Hepatoblastoma: A Report from the Children’s Oncology Group (COG) and the Utah Population Database (UPDB)

    PubMed Central

    Venkatramani, Rajkumar; Spector, Logan G.; Georgieff, Michael; Tomlinson, Gail; Krailo, Mark; Malogolowkin, Marcio; Kohlmann, Wendy; Curtin, Karen; Fonstad, Rachel K.; Schiffman, Joshua D.

    2014-01-01

    Beckwith-Wiedemann Syndrome (BWS) and Familial Adenomatous Polyposis (FAP) are known to predispose to hepatoblastoma (HB). A case control study was conducted through the Children’s Oncology Group (COG) to study the association of HB with isolated congenital abnormalities. Cases (N = 383) were diagnosed between 2000 and 2008. Controls (N = 387) were recruited from state birth registries, frequency matched for sex, region, year of birth, and birth weight. Data on congenital abnormalities among subjects and covariates were obtained by maternal telephone interview. Odds ratios (OR) and 95% confidence intervals (CI) describing the association between congenital abnormalities with HB, adjusted for sex, birth weight, maternal age and maternal education, were calculated using unconditional logistic regression. There was a significant association of HB with kidney, bladder, or sex organ abnormalities (OR = 4.75; 95% CI: 1.74–13) which appeared to be specific to kidney/bladder defects (OR = 4.3; 95% CI: 1.2–15.3) but not those of sex organs (OR = 1.24; 95% CI: 0.37–4.1). Elevated but non-significant ORs were found for spina bifida or other spinal defects (OR = 2.12; 95% CI: 0.39–11.7), large or multiple birthmarks (OR = 1.33; 95% CI: 0.81–2.21). The results were validated through the Utah Population Database (UPDB), a statewide population-based registry linking birth certificates, medical records, and cancer diagnoses. In the UPDB, there were 29 cases and 290 population controls matched 10:1 on sex and birth year. Consistent with the COG findings, kidney/bladder defects were associated with hepatoblastoma. These results confirm the association of HB with kidney/bladder abnormalities. PMID:24934283

  19. Direct heuristic dynamic programming for damping oscillations in a large power system.

    PubMed

    Lu, Chao; Si, Jennie; Xie, Xiaorong

    2008-08-01

    This paper applies a neural-network-based approximate dynamic programming method, namely, the direct heuristic dynamic programming (direct HDP), to a large power system stability control problem. The direct HDP is a learning- and approximation-based approach to addressing nonlinear coordinated control under uncertainty. One of the major design parameters, the controller learning objective function, is formulated to directly account for network-wide low-frequency oscillation with the presence of nonlinearity, uncertainty, and coupling effect among system components. Results include a novel learning control structure based on the direct HDP with applications to two power system problems. The first case involves static var compensator supplementary damping control, which is used to provide a comprehensive evaluation of the learning control performance. The second case aims at addressing a difficult complex system challenge by providing a new solution to a large interconnected power network oscillation damping control problem that frequently occurs in the China Southern Power Grid.

  20. Occupational factors and pancreatic cancer.

    PubMed Central

    Norell, S; Ahlbom, A; Olin, R; Erwald, R; Jacobson, G; Lindberg-Navier, I; Wiechel, K L

    1986-01-01

    The relation between occupational factors and pancreatic cancer has been studied by two different approaches: a population based case-control study with two series of controls and a retrospective cohort study based on register data. With both approaches, some support was found for an association with occupational exposure to petroleum products. Associations were also indicated with exposure to paint thinner (case-control study) and work in painting and in paint and varnish factories (cohort study), for exposure to detergents, floor cleaning agents, or polish (case-control study) and with floor polishing or window cleaning (cohort study), and for exposure to refuse (case-control study) and work in refuse disposal plants (cohort study). PMID:3790458

  1. Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression.

    PubMed

    Quteineh, Lina; Preisig, Martin; Rivera, Margarita; Milaneschi, Yuri; Castelao, Enrique; Gholam-Rezaee, Mehdi; Vandenberghe, Frederik; Saigi-Morgui, Nuria; Delacrétaz, Aurélie; Cardinaux, Jean-René; Willemsen, Gonneke; Boomsma, Dorret I; Penninx, Brenda W J H; Ching-López, Ana; Conus, Philippe; Eap, Chin B

    2016-07-01

    Psychiatric disorders have been hypothesized to share common etiological pathways with obesity, suggesting related neurobiological bases. We aimed to examine whether CRTC1 polymorphisms were associated with major depressive disorder (MDD) and to test the association of these polymorphisms with obesity markers in several large case-control samples with MDD. The association between CRTC1 polymorphisms and MDD was investigated in three case-control samples with MDD (PsyCoLaus n1=3,362, Radiant n2=3,148 and NESDA/NTR n3=4,663). The effect of CRTC1 polymorphisms on obesity markers was then explored. CRTC1 polymorphisms were not associated with MDD in the three samples. CRTC1 rs6510997C>T was significantly associated with fat mass in the PsyCoLaus study. In fact, a protective effect of this polymorphism was found in MDD cases (n=1,434, β=-1.32%, 95% CI -2.07 to -0.57, p<0.001), but not in controls. In the Radiant study, CRTC1 polymorphisms were associated with BMI, exclusively in individuals with MDD (n=2,138, β=-0.75kg/m(2), 95% CI -1.30 to -0.21, p=0.007), while no association with BMI was found in the NESDA/NTR study. Estimated fat mass using bioimpedance that capture more accurately adiposity was only present in the PsyCoLaus sample. CRTC1 polymorphisms seem to play a role with obesity markers in individuals with MDD rather than non-depressive individuals. Therefore, the weak association previously reported in the population-based samples was driven by cases diagnosed with lifetime MDD. However, CRTC1 seems not to be implicated directly in the development of psychiatric diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Association between mobile phone traffic volume and road crash fatalities: A population-based case-crossover study.

    PubMed

    Gariazzo, Claudio; Stafoggia, Massimo; Bruzzone, Silvia; Pelliccioni, Armando; Forastiere, Francesco

    2018-06-01

    Use of mobile phones while driving is known to cause crashes with possible fatalities. Different habits of mobile phone use might be distracting forces and display differential impacts on accident risk; the assessment of the relative importance is relevant to implement prevention, mitigation, and control measures. This study aimed to assess the relationship between the use of mobile phones at population level and road crash fatalities in large urban areas. Data on road crashes with fatalities were collected from seven Italian metropolitan areas and matched in time and space with high resolution mobile phone traffic volume data about calls, texts, Internet connections and upload/download data. A case-crossover study design was applied to estimate the relative risks of road accident for increases in each type of mobile phone traffic volumes in underlying population present in the small areas where accidents occurred. Effect modification was evaluated by weekday/weekend, hour of the day, meteorological conditions, and street densities. Positive associations between road crashes rates and the number of calls, texts, and Internet connections were found, with incremental risks of 17.2% (95% Confidence Interval [CI] 7.7, 27.6), 8.4% (CI 0.7, 16.8), and 54.6% (CI 34.0, 78.5) per increases (at 15 min intervals) of 5 calls/100 people, 3 text/100 people, and 40 connections/100 people, respectively. Small differences across cities were detected. Working days, nighttime and morning hours were associated with greater phone use and more road accidents. The relationship between mobile phone use and road fatalities at population level is strong. Strict controls on cellular phone in the vehicle may results in a large health benefit. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Epidemiologic study of residential proximity to transmission lines and childhood cancer in California: description of design, epidemiologic methods and study population

    PubMed Central

    Kheifets, Leeka; Crespi, Catherine M; Hooper, Chris; Oksuzyan, Sona; Cockburn, Myles; Ly, Thomas; Mezei, Gabor

    2015-01-01

    We conducted a large epidemiologic case-control study in California to examine the association between childhood cancer risk and distance from the home address at birth to the nearest high-voltage overhead transmission line as a replication of the study of Draper et al. in the United Kingdom. We present a detailed description of the study design, methods of case ascertainment, control selection, exposure assessment and data analysis plan. A total of 5788 childhood leukemia cases and 3308 childhood central nervous system cancer cases (included for comparison) and matched controls were available for analysis. Birth and diagnosis addresses of cases and birth addresses of controls were geocoded. Distance from the home to nearby overhead transmission lines was ascertained on the basis of the electric power companies’ geographic information system (GIS) databases, additional Google Earth aerial evaluation and site visits to selected residences. We evaluated distances to power lines up to 2000 m and included consideration of lower voltages (60–69 kV). Distance measures based on GIS and Google Earth evaluation showed close agreement (Pearson correlation >0.99). Our three-tiered approach to exposure assessment allowed us to achieve high specificity, which is crucial for studies of rare diseases with low exposure prevalence. PMID:24045429

  4. Coffee and tea consumption and risk of leukaemia in an adult population: A reanalysis of the Italian multicentre case-control study.

    PubMed

    Parodi, Stefano; Merlo, Domenico Franco; Stagnaro, Emanuele

    2017-04-01

    Coffee and tea are the most frequently consumed beverages in the world. Their potential effect on the risk of developing different types of malignancies has been largely investigated, but studies on leukaemia in adults are scarce. The present investigation is aimed at evaluating the potential role of regular coffee and tea intake on the risk of adult leukaemia by reanalysing a large population based case-control study carried out in Italy, a country with a high coffee consumption and a low use of green tea. Interviewed subjects, recruited between 1990 and 1993 in 11 Italian areas, included 1771 controls and 651 leukaemia cases. Association between Acute Myeloid Leukaemia (AML), Acute Lymphoid Leukaemia, Chronic Myeloid Leukaemia, Chronic Lymphoid Leukaemia, and use of coffee and tea was evaluated by standard logistic regression. Odds Ratios (OR) were estimated adjusting for the following potential confounders: gender, age, residence area, smoking habit, educational level, previous chemotherapy treatment, alcohol consumption and exposure to electromagnetic fields, radiation, pesticides and aromatic hydrocarbons. No association was observed between regular use of coffee and any type of leukaemia. A small protective effect of tea intake was found among myeloid malignancies, which was more evident among AML (OR=0.68, 95%CI: 0.49-0.94). However, no clear dose-response relation was found. The lower risk of leukaemia among regular coffee consumers, reported by a few of previous small studies, was not confirmed. The protective effect of tea on the AML risk is only partly consistent with results from other investigations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Haemorrhoids are associated with erectile dysfunction: a population-based study.

    PubMed

    Keller, J J; Lin, H-C

    2012-12-01

    Haemorrhoids are associated with regional vascular abnormalities and rectal pain, which are hypothesized to increase the risk of erectile dysfunction (ED); however, few studies have investigated the association between ED and haemorrhoids. This case-control study aimed to estimate the association between haemorrhoids and ED by using a population-based data in Taiwan. We identified 6,310 patients with ED as cases and randomly selected 31,550 controls. Conditional logistic regression was performed to compute the odds ratio (OR) for having been previously diagnosed with haemorrhoids between cases and controls. The results show that haemorrhoids were found to be present among 1,572 (24.9%) cases and 4,491 (14.20%) controls. The OR for prior haemorrhoids among cases was 1.90 (95% CI = 1.78-2.03) when compared with controls after adjusting for monthly income, geographical location, hypertension, diabetes, coronary heart disease, hyperlipidemia, obesity and alcohol abuse/alcohol dependence syndrome. Younger cases demonstrated a higher risk for prior haemorrhoids when compared with controls. In particular, the adjusted OR among cases <30 years old was 3.71 (95% CI = 2.74-5.02) when compared with controls. We concluded that there was an association between ED and a prior diagnosis of haemorrhoids. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

  6. Comparative study of control selection in a national population-based case-control study: Estimating risk of smoking on cancer deaths in Chinese men.

    PubMed

    Jiang, Jingmei; Liu, Boqi; Nasca, Philip C; Han, Wei; Zou, Xiaonong; Zeng, Xianjia; Tian, Xiaobing; Wu, Yanping; Zhao, Ping; Li, Junyao

    2009-10-28

    To assess the validation of a novel control selection design by comparing the consistency between the new design and a routine design in a large case-control study that was incorporated into a nationwide mortality survey in China. A nationwide mortality study was conducted during 1989-1991. Surviving spouses or other relatives of all adults who died during 1986-1988 provided detailed information about their own as well as the deceased person's smoking history. In this study, 130,079 males who died of various smoking-related cancers at age 35 or over were taken as cases, while 103,248 male surviving spouses (same age range with cases) of women who died during the same period and 49,331 males who died from causes other than those related to smoking were used as control group 1 and control group 2, respectively. Consistency in the results when comparing cases with each of the control groups was assessed. Consistency in the results was observed in the analyses using different control groups although cancer deaths varied with region and age. Equivalence could be ascertained using a 15% criterion in most cancer deaths which had high death rates in urban areas, but they were uncertain for most cancers in rural areas irrespective of whether the hypothesis testing showed significant differences or not. Sex-matched living spouse control design as an alternative control selection for a case-control study is valid and feasible, and the basic principles of the equivalence study are also supported by epidemiological survey data.

  7. Neurocognitive performance in family-based and case-control studies of schizophrenia

    PubMed Central

    Gur, Ruben C.; Braff, David L.; Calkins, Monica E.; Dobie, Dorcas J.; Freedman, Robert; Green, Michael F.; Greenwood, Tiffany A.; Lazzeroni, Laura C.; Light, Gregory A.; Nuechterlein, Keith H.; Olincy, Ann; Radant, Allen D.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Stone, William S.; Sugar, Catherine A.; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Gur, Raquel E.

    2014-01-01

    Background Neurocognitive deficits in schizophrenia (SZ) are established and the Consortium on the Genetics of Schizophrenia (COGS) investigated such measures as endophenotypes in family-based (COGS-1) and case-control (COGS-2) studies. By requiring family participation, family-based sampling may result in samples that vary demographically and perform better on neurocognitive measures. Methods The Penn computerized neurocognitive battery (CNB) evaluates accuracy and speed of performance for several domains and was administered across sites in COGS-1 and COGS-2. Most tests were included in both studies. COGS-1 included 328 patients with SZ and 497 healthy comparison subjects (HCS) and COGS-2 included 1195 patients and 1009 HCS. Results Demographically, COGS-1 participants were younger, more educated, with more educated parents and higher estimated IQ compared to COGS-2 participants. After controlling for demographics, the two samples produced very similar performance profiles compared to their respective controls. As expected, performance was better and with smaller effect sizes compared to controls in COGS-1 relative to COGS-2. Better performance was most pronounced for spatial processing while emotion identification had large effect sizes for both accuracy and speed in both samples. Performance was positively correlated with functioning and negatively with negative and positive symptoms in both samples, but correlations were attenuated in COGS-2, especially with positive symptoms. Conclusions Patients ascertained through family-based design have more favorable demographics and better performance on some neurocognitive domains. Thus, studies that use case-control ascertainment may tap into populations with more severe forms of illness that are exposed to less favorable factors compared to those ascertained with family-based designs. PMID:25432636

  8. Participatory Risk Mapping of Malaria Vector Exposure in Northern South America using Environmental and Population Data

    PubMed Central

    Fuller, D.O.; Troyo, A.; Alimi, T.O.; Beier, J.C.

    2014-01-01

    Malaria elimination remains a major public health challenge in many tropical regions, including large areas of northern South America. In this study, we present a new high spatial resolution (90 × 90 m) risk map for Colombia and surrounding areas based on environmental and human population data. The map was created through a participatory multi-criteria decision analysis in which expert opinion was solicited to determine key environmental and population risk factors, different fuzzy functions to standardize risk factor inputs, and variable factor weights to combine risk factors in a geographic information system. The new risk map was compared to a map of malaria cases in which cases were aggregated to the municipio (municipality) level. The relationship between mean municipio risk scores and total cases by muncípio showed a weak correlation. However, the relationship between pixel-level risk scores and vector occurrence points for two dominant vector species, Anopheles albimanus and An. darlingi, was significantly different (p < 0.05) from a random point distribution, as was a pooled point distribution for these two vector species and An. nuneztovari. Thus, we conclude that the new risk map derived based on expert opinion provides an accurate spatial representation of risk of potential vector exposure rather than malaria transmission as shown by the pattern of malaria cases, and therefore it may be used to inform public health authorities as to where vector control measures should be prioritized to limit human-vector contact in future malaria outbreaks. PMID:24976656

  9. Association of zolpidem use and subsequent increased risk of epilepsy: a population-based, case-control study.

    PubMed

    Harnod, Tomor; Wang, Yu-Chiao; Sung, Fung-Chang; Kao, Chia-Hung

    2014-10-01

    To evaluate the impact of long-term zolpidem use on the subsequent risk of epilepsy. We used data from the National Health Insurance system of Taiwan to conduct a population-based case-control study. We identified 4,972 newly diagnosed epilepsy patients (ICD-9-CM code 345) for the period of 2005-2010 as cases. For each epilepsy case, 4 controls without a history of epilepsy were randomly selected from the rest of the population. Zolpidem was used as a predictor of epilepsy. Patients with epilepsy exhibited an adjusted odds ratio (OR) of 1.86 (95% CI, 1.70-2.03) and were, therefore, more strongly associated with zolpidem exposure than control patients were. The adjusted OR of epilepsy increased with the increase of mean zolpidem exposure (g/y). Compared with the OR of nonusers, the adjusted OR was 1.64 (95% CI, 1.44-1.86) for those who had taken < 1.0 g/y of zolpidem and 2.38 (95% CI, 2.06-2.74) for those who had taken ≥ 20.0 g/y of zolpidem. An adjusted OR of 3.55 (95% CI, 2.94-4.28) was noted to be associated with epilepsy when users had stopped taking the drug less than 7 days earlier. The estimated risk declined to an OR of 1.62 (95% CI, 1.47-1.78) when users had stopped taking the drug more than 90 days earlier. This population-based, retrospective case-control study revealed a possible increase in epilepsy risk with zolpidem use, at either typical or supratherapeutic doses. These findings might stimulate public interest in safety issues regarding zolpidem use. © Copyright 2014 Physicians Postgraduate Press, Inc.

  10. Early childhood measles vaccinations are not associated with paediatric IBD: a population-based analysis.

    PubMed

    Shaw, Souradet Y; Blanchard, James F; Bernstein, Charles N

    2015-04-01

    Early childhood vaccinations have been hypothesized to contribute to the emergence of paediatric inflammatory bowel disease [IBD] in developed countries. Using linked population-based administrative databases, we aimed to explore the association between vaccination with measles-containing vaccines and the risk for IBD. This was a case-control study using the University of Manitoba IBD Epidemiology Database [UMIBDED]. The UMIBDED was linked to the Manitoba Immunization Monitoring System [MIMS], a population-based database of immunizations administered in Manitoba. All paediatric IBD cases in Manitoba, born after 1989 and diagnosed before March 31, 2008, were included. Controls were matched to cases on the basis of age, sex, and region of residence at time of diagnosis. Measles-containing vaccinations received in the first 2 years of life were documented, with vaccinations categorized as 'None' or 'Complete', with completeness defined according to Manitoba's vaccination schedule. Conditional logistic regression models were fitted to the data, with models adjusted for physician visits in the first 2 years of life and area-level socioeconomic status at case date. A total of 951 individuals [117 cases and 834 controls] met eligibility criteria, with average age of diagnosis among cases at 11 years. The proportion of IBD cases with completed vaccinations was 97%, compared with 94% of controls. In models adjusted for physician visits and area-level socioeconomic status, no statistically significant association was detected between completed measles vaccinations and the risk of IBD (adjusted odds ratio [AOR]: 1.5; 95% confidence interval [CI]: 0.5-4.4; p = 0.419]. No significant association between completed measles-containing vaccination in the first 2 years of life and paediatric IBD could be demonstrated in this population-based study. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  11. A genetic study and meta-analysis of the genetic predisposition of prostate cancer in a Chinese population.

    PubMed

    Marzec, Jacek; Mao, Xueying; Li, Meiling; Wang, Meilin; Feng, Ninghan; Gou, Xin; Wang, Guomin; Sun, Zan; Xu, Jianfeng; Xu, Hua; Zhang, Xiaoping; Zhao, Shan-Chao; Ren, Guoping; Yu, Yongwei; Wu, Yudong; Wu, Ji; Xue, Yao; Zhou, Bo; Zhang, Yanling; Xu, Xingxing; Li, Jie; He, Weiyang; Benlloch, Sara; Ross-Adams, Helen; Chen, Li; Li, Jucong; Hong, Yingqia; Kote-Jarai, Zsofia; Cui, Xingang; Hou, Jianguo; Guo, Jianming; Xu, Lei; Yin, Changjun; Zhou, Yuanping; Neal, David E; Oliver, Tim; Cao, Guangwen; Zhang, Zhengdong; Easton, Douglas F; Chelala, Claude; Al Olama, Ali Amin; Eeles, Rosalind A; Zhang, Hongwei; Lu, Yong-Jie

    2016-04-19

    Prostate cancer predisposition has been extensively investigated in European populations, but there have been few studies of other ethnic groups. To investigate prostate cancer susceptibility in the under-investigated Chinese population, we performed single-nucleotide polymorphism (SNP) array analysis on a cohort of Chinese cases and controls and then meta-analysis with data from the existing Chinese prostate cancer genome-wide association study (GWAS). Genotyping 211,155 SNPs in 495 cases and 640 controls of Chinese ancestry identified several new suggestive Chinese prostate cancer predisposition loci. However, none of them reached genome-wide significance level either by meta-analysis or replication study. The meta-analysis with the Chinese GWAS data revealed that four 8q24 loci are the main contributors to Chinese prostate cancer risk and the risk alleles from three of them exist at much higher frequencies in Chinese than European populations. We also found that several predisposition loci reported in Western populations have different effect on Chinese men. Therefore, this first extensive single-nucleotide polymorphism study of Chinese prostate cancer in comparison with European population indicates that four loci on 8q24 contribute to a great risk of prostate cancer in a considerable large proportion of Chinese men. Based on those four loci, the top 10% of the population have six- or two-fold prostate cancer risk compared with men of the bottom 10% or median risk respectively, which may facilitate the design of prostate cancer genetic risk screening and prevention in Chinese men. These findings also provide additional insights into the etiology and pathogenesis of prostate cancer.

  12. Representativeness of Tuberculosis Genotyping Surveillance in the United States, 2009-2010.

    PubMed

    Shak, Emma B; France, Anne Marie; Cowan, Lauren; Starks, Angela M; Grant, Juliana

    2015-01-01

    Genotyping of Mycobacterium tuberculosis isolates contributes to tuberculosis (TB) control through detection of possible outbreaks. However, 20% of U.S. cases do not have an isolate for testing, and 10% of cases with isolates do not have a genotype reported. TB outbreaks in populations with incomplete genotyping data might be missed by genotyping-based outbreak detection. Therefore, we assessed the representativeness of TB genotyping data by comparing characteristics of cases reported during January 1, 2009-December 31, 2010, that had a genotype result with those cases that did not. Of 22,476 cases, 14,922 (66%) had a genotype result. Cases without genotype results were more likely to be patients <19 years of age, with unknown HIV status, of female sex, U.S.-born, and with no recent history of homelessness or substance abuse. Although cases with a genotype result are largely representative of all reported U.S. TB cases, outbreak detection methods that rely solely on genotyping data may underestimate TB transmission among certain groups.

  13. Representativeness of Tuberculosis Genotyping Surveillance in the United States, 2009–2010

    PubMed Central

    Shak, Emma B.; Cowan, Lauren; Starks, Angela M.; Grant, Juliana

    2015-01-01

    Genotyping of Mycobacterium tuberculosis isolates contributes to tuberculosis (TB) control through detection of possible outbreaks. However, 20% of U.S. cases do not have an isolate for testing, and 10% of cases with isolates do not have a genotype reported. TB outbreaks in populations with incomplete genotyping data might be missed by genotyping-based outbreak detection. Therefore, we assessed the representativeness of TB genotyping data by comparing characteristics of cases reported during January 1, 2009–December 31, 2010, that had a genotype result with those cases that did not. Of 22,476 cases, 14,922 (66%) had a genotype result. Cases without genotype results were more likely to be patients <19 years of age, with unknown HIV status, of female sex, U.S.-born, and with no recent history of homelessness or substance abuse. Although cases with a genotype result are largely representative of all reported U.S. TB cases, outbreak detection methods that rely solely on genotyping data may underestimate TB transmission among certain groups. PMID:26556930

  14. Maternal underweight and obesity and risk of orofacial clefts in a large international consortium of population-based studies.

    PubMed

    Kutbi, Hebah; Wehby, George L; Moreno Uribe, Lina M; Romitti, Paul A; Carmichael, Suzan; Shaw, Gary M; Olshan, Andrew F; DeRoo, Lisa; Rasmussen, Sonja A; Murray, Jeffrey C; Wilcox, Allen; Lie, Rolv T; Munger, Ronald G

    2017-02-01

    Evidence on association of maternal pre-pregnancy weight with risk of orofacial clefts is inconsistent. Six large case-control studies of orofacial clefts from Northern Europe and the USA were included in analyses pooling individual-level data. Cases included 4943 mothers of children with orofacial clefts (cleft lip only: 1135, cleft palate with cleft lip: 2081, cleft palate only: 1727) and controls included 10 592 mothers of unaffected children. Association of orofacial cleft risk with pre-pregnancy maternal weight classified by level of body mass index (BMI, kg/m 2 ) was evaluated using logistic regression adjusting for multiple covariates. Cleft palate, both alone and with cleft lip (CP+/-CL), was associated with maternal class II+ pre-pregnancy obesity (≥ 35)compared with normal weight [adjusted odds ratio (aOR) = 1.36; 95% confidence interval (CI) = 1.16, 1.58]. CP+/-CL was marginally associated with maternal underweight (aOR = 1.16; 95% CI = 0.98, 1.36). Cleft lip alone was not associated with BMI. In this largest population-based study to date, we found an increased risk of cleft palate, with or without cleft lip, in class II+ obese mothers compared with normal-weight mothers; underweight mothers may also have an increased risk, but this requires further study. These results also suggest that extremes of weight may have a specific effect on palatal development. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

  15. Occupation and lung cancer in Shanghai: a case-control study.

    PubMed Central

    Levin, L I; Zheng, W; Blot, W J; Gao, Y T; Fraumeni, J F

    1988-01-01

    Occupation was evaluated as a potential risk factor for lung cancer as part of a large population based case-control study conducted in the ten urban districts of Shanghai. A total of 733 newly diagnosed cases of male lung cancer and 760 controls selected from the general population was interviewed to obtain lifetime occupational histories and information on smoking and other factors. Of the approximately 25 major industrial titles examined, significantly raised risks, adjusted for smoking, were found for employment in agricultural production (odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.0-2.6). A concomitant increase was detected for farmers (OR = 1.6, 95% CI = 1.0-2.5) when 35 major occupational titles were examined. There was a 70% excess among workers in the chemical industry (OR = 1.7, 95% CI = 0.9-3.1) and a significant decrease among textile industry workers (OR = 0.7, 95% CI = 0.5-1.0). Raised risks of 30% to 80% were associated with reported job exposures to wood and coal dusts, smoke from burning fuels, and chemical fumes. Employment categories were also examined for 672 cases and 735 controls among women, but small numbers in many of the industrial and occupational categories precluded detailed analyses. The largest excess risk among women (OR = 5.1, 95% CI 1.3-23.5) was among glass products workers. Although cigarette smoking was the dominant cause of lung cancer among men and a significant risk factor among women in Shanghai, these findings suggest the importance of certain workplace exposures and offer leads to occupational carcinogens. PMID:3395581

  16. Associations between trans fatty acid consumption and colon cancer among Whites and African Americans in the North Carolina colon cancer study I.

    PubMed

    Vinikoor, Lisa C; Satia, Jessie A; Schroeder, Jane C; Millikan, Robert C; Martin, Christopher F; Ibrahim, Joseph G; Sandler, Robert S

    2009-01-01

    Disparities in incidence and mortality rates of colon cancer exist between Whites and African Americans. Prior studies examined the association between trans fatty acid consumption and colorectal cancer, but none assessed this possible relationship within a large study population of African Americans and Whites. Using data from a population-based, case-control study in North Carolina, we investigated this association with attention to possible racial differences. Cases and matched controls were queried on demographic characteristics, lifestyle factors, medical history, and diet. Cases reported higher daily consumption (g/day) of trans fatty acids (mean = 5.9, SD = 2.9, median = 5.5, IQR = 3.8-7.5) compared to controls (mean = 5.2, SD = 2.4, median = 4.7, IQR = 3.5-6.4). Energy-adjusted trans fatty acid consumption was not associated with colon cancer. Compared to participants in the lowest quartile of consumption, those in the highest quartile had an adjusted odds ratio of 1.01 (95% confidence interval 0.69, 1.49) for Whites and 0.99 (95% confidence interval 0.61, 1.62) for African Americans. No association was found between increased consumption of trans fatty acid and specific tumor location (proximal or distal colon). In conclusion, trans fatty acid consumption is not associated with colon cancer and does not contribute to disparities in colon cancer rates.

  17. Spatial processes decouple management from objectives in a heterogeneous landscape: predator control as a case study.

    PubMed

    Mahoney, Peter J; Young, Julie K; Hersey, Kent R; Larsen, Randy T; McMillan, Brock R; Stoner, David C

    2018-04-01

    Predator control is often implemented with the intent of disrupting top-down regulation in sensitive prey populations. However, ambiguity surrounding the efficacy of predator management, as well as the strength of top-down effects of predators in general, is often exacerbated by the spatially implicit analytical approaches used in assessing data with explicit spatial structure. Here, we highlight the importance of considering spatial context in the case of a predator control study in south-central Utah. We assessed the spatial match between aerial removal risk in coyotes (Canis latrans) and mule deer (Odocoileus hemionus) resource selection during parturition using a spatially explicit, multi-level Bayesian model. With our model, we were able to evaluate spatial congruence between management action (i.e., coyote removal) and objective (i.e., parturient deer site selection) at two distinct scales: the level of the management unit and the individual coyote removal. In the case of the former, our results indicated substantial spatial heterogeneity in expected congruence between removal risk and parturient deer site selection across large areas, and is a reflection of logistical constraints acting on the management strategy and differences in space use between the two species. At the level of the individual removal, we demonstrated that the potential management benefits of a removed coyote were highly variable across all individuals removed and in many cases, spatially distinct from parturient deer resource selection. Our methods and results provide a means of evaluating where we might anticipate an impact of predator control, while emphasizing the need to weight individual removals based on spatial proximity to management objectives in any assessment of large-scale predator control. Although we highlight the importance of spatial context in assessments of predator control strategy, we believe our methods are readily generalizable in any management or large-scale experimental framework where spatial context is likely an important driver of outcomes. © 2018 by the Ecological Society of America.

  18. Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case-Control Study in Spain and Italy.

    PubMed

    Villanueva, Cristina M; Gracia-Lavedan, Esther; Bosetti, Cristina; Righi, Elena; Molina, Antonio José; Martín, Vicente; Boldo, Elena; Aragonés, Nuria; Perez-Gomez, Beatriz; Pollan, Marina; Acebo, Ines Gomez; Altzibar, Jone M; Zabala, Ana Jiménez; Ardanaz, Eva; Peiró, Rosana; Tardón, Adonina; Chirlaque, Maria Dolores; Tavani, Alessandra; Polesel, Jerry; Serraino, Diego; Pisa, Federica; Castaño-Vinyals, Gemma; Espinosa, Ana; Espejo-Herrera, Nadia; Palau, Margarita; Moreno, Victor; La Vecchia, Carlo; Aggazzotti, Gabriella; Nieuwenhuijsen, Mark J; Kogevinas, Manolis

    2017-01-01

    Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent. We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer. A multicenter case-control study was conducted in Spain and Italy in 2008-2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, type of water consumed in each residence, frequency and duration of showering/bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant's residential tap water (micrograms/liter; from age 18 to 2 years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (micrograms/day). We analyzed 2,047 cases and 3,718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0-174), 17 (0-63), and 9 (0-145) μg/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR = 0.92, 95% CI: 0.66, 1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR = 0.31, 95% CI: 0.24, 0.41 for highest vs. lowest quartile). Brominated THM concentrations showed a positive association among men in the highest versus the lowest quartile (OR = 1.43, 95% CI: 0.83, 2.46). Patterns of association were similar for estimated average THM ingestion through residential water consumption. We did not find clear evidence of an association between detailed estimates of lifetime total THM exposure and colorectal cancer in our large case-control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings should be confirmed in other study populations. Citation: Villanueva CM, Gracia-Lavedan E, Bosetti C, Righi E, Molina AJ, Martín V, Boldo E, Aragonés N, Perez-Gomez B, Pollan M, Gomez Acebo I, Altzibar JM, Jiménez Zabala A, Ardanaz E, Peiró R, Tardón A, Chirlaque MD, Tavani A, Polesel J, Serraino D, Pisa F, Castaño-Vinyals G, Espinosa A, Espejo-Herrera N, Palau M, Moreno V, La Vecchia C, Aggazzotti G, Nieuwenhuijsen MJ, Kogevinas M. 2017. Colorectal cancer and long-term exposure to trihalomethanes in drinking water: a multicenter case---control study in Spain and Italy. Environ Health Perspect 125:56-65; http://dx.doi.org/10.1289/EHP155.

  19. Occupational risk factors for brain cancer: a population-based case-control study in Iowa.

    PubMed

    Zheng, T; Cantor, K P; Zhang, Y; Keim, S; Lynch, C F

    2001-04-01

    A number of occupations and industries have been inconsistently associated with the risk of brain cancer. To further explore possible relationships, we conducted a population-based case-control study of brain glioma in the state of Iowa, involving 375 histologically confirmed incident cases and 2434 population-based controls. Among men, the industries and/or occupations that had a significantly increased risk for employment of more than 10 years included roofing, siding, and sheet metalworking; newspaper work; rubber and plastics products, particularly tires and inner tubes; miscellaneous manufacturing industries; wholesale trade of durable goods, grain, and field beans; cleaning and building service occupations; miscellaneous mechanics and repairers; and janitors and cleaners. Subjects who worked in plumbing, heating, and air conditioning; electrical services; gasoline service stations; and military occupations also experienced a significantly increased risk. Among women, significant excess risk was observed for occupations in agricultural services and farming, apparel and textile products, electrical and electronic equipment manufacturing, various retail sales, record-keeping, and restaurant service. Workers in industries with a potential for gasoline or motor exhaust exposures experienced a non-significant excess risk of brain glioma.

  20. Effectiveness of open versus endovascular abdominal aortic aneurysm repair in population settings: A systematic review of statewide databases.

    PubMed

    Williams, Christopher R; Brooke, Benjamin S

    2017-10-01

    Patient outcomes after open abdominal aortic aneurysm and endovascular aortic aneurysm repair have been widely reported from several large, randomized, controlled trials. It is not clear whether these trial outcomes are representative of abdominal aortic aneurysm repair procedures performed in real-world hospital settings across the United States. This study was designed to evaluate population-based outcomes after endovascular aortic aneurysm repair versus open abdominal aortic aneurysm repair using statewide inpatient databases and examine how they have helped improve our understanding of abdominal aortic aneurysm repair. A systematic search of MEDLINE, EMBASE, and CINAHL databases was performed to identify articles comparing endovascular aortic aneurysm repair and open abdominal aortic aneurysm repair using data from statewide inpatient databases. This search was limited to studies published in the English language after 1990, and abstracts were screened and abstracted by 2 authors. Our search yielded 17 studies published between 2004 and 2016 that used data from 29 different statewide inpatient databases to compare endovascular aortic aneurysm repair versus open abdominal aortic aneurysm repair. These studies support the randomized, controlled trial results, including a lower mortality associated with endovascular aortic aneurysm repair extended from the perioperative period up to 3 years after operation, as well as a higher complication rate after endovascular aortic aneurysm repair. The evidence from statewide inpatient database analyses has also elucidated trends in procedure volume, patient case mix, volume-outcome relationships, and health care disparities associated with endovascular aortic aneurysm repair versus open abdominal aortic aneurysm repair. Population analyses of endovascular aortic aneurysm repair and open abdominal aortic aneurysm repair using statewide inpatient databases have confirmed short- and long-term mortality outcomes obtained from large, randomized, controlled trials. Moreover, these analyses have allowed us to assess the effect of endovascular aortic aneurysm repair adoption on population outcomes and patient case mix over time. Published by Elsevier Inc.

  1. Siemens Immulite Aspergillus-specific IgG assay for chronic pulmonary aspergillosis diagnosis.

    PubMed

    Page, Iain D; Richardson, Malcolm D; Denning, David W

    2018-05-14

    Chronic pulmonary aspergillosis (CPA) complicates underlying lung disease, including treated tuberculosis. Measurement of Aspergillus-specific immunoglobulin G (IgG) is a key diagnostic step. Cutoffs have been proposed based on receiver operating characteristic (ROC) curve analyses comparing CPA cases to healthy controls, but performance in at-risk populations with underlying lung disease is unclear. We evaluated optimal cutoffs for the Siemens Immulite Aspergillus-specific IgG assay for CPA diagnosis in relation to large groups of healthy and diseased controls with treated pulmonary tuberculosis. Sera from 241 patients with CPA attending the UK National Aspergillosis Centre, 299 Ugandan blood donors (healthy controls), and 398 Ugandans with treated pulmonary tuberculosis (diseased controls) were tested. Radiological screening removed potential CPA cases from diseased controls (234 screened diseased controls). ROC curve analyses were performed and optimal cutoffs identified by Youden J statistic. CPA versus control ROC area under curve (AUC) results were: healthy controls 0.984 (95% confidence interval 0.972-0.997), diseased controls 0.972 (0.959-0.985), screened diseased controls 0.979 (0.967-0.992). Optimal cutoffs were: healthy controls 15 mg/l (94.6% sensitivity, 98% specificity), unscreened diseased controls 15 mg/l (94.6% sensitivity, 94.5% specificity), screened diseased controls 25 mg/l (92.9% sensitivity, 98.7% specificity). Results were similar in healthy and diseased controls. We advocate a cutoff of 20 mg/l as this is the midpoint of the range of optimal cutoffs. Cutoffs calculated in relation to healthy controls for other assays are likely to remain valid for use in a treated tuberculosis population.

  2. Brief Report: Prevalence of Self-Injurious Behaviors among Children with Autism Spectrum Disorder--A Population-Based Study

    ERIC Educational Resources Information Center

    Soke, Gnakub N.; Rosenberg, Steven A.; Hamman, Richard F.; Fingerlin, Tasha; Robinson, Cordelia; Carpenter, Laura; Giarelli, Ellen; Lee, Li-Ching; Wiggins, Lisa D.; Durkin, Maureen S.; DiGuiseppi, Carolyn

    2016-01-01

    Self-injurious behaviors (SIB) have been reported in more than 30% of children with an autism spectrum disorder (ASD) in clinic-based studies. This study estimated the prevalence of SIB in a large population-based sample of children with ASD in the United States. A total of 8,065 children who met the surveillance case definition for ASD in the…

  3. The evaluation of the National Long Term Care Demonstration. 4. Case management under channeling.

    PubMed Central

    Phillips, B R; Kemper, P; Applebaum, R A

    1988-01-01

    The channeling demonstration involved provision of comprehensive case management and direct service expansion. This article considers the former. Under both models, comprehensive case management was implemented largely as intended; moreover, channeling substantially increased the receipt of comprehensive care management. However, channeling was not a pure test of the effect of comprehensive case management: roughly 10-20 percent of control group members received comparable case management services. This was particularly the case for the financial control model. Thus, the demonstration was not a test of case management compared to no case management; rather, it compared channeling case management to the existing community care system, which already was providing comprehensive case management to some of the population eligible for channeling. PMID:3130331

  4. Drug interactions with phenprocoumon and the risk of serious haemorrhage: a nested case-control study in a large population-based German database.

    PubMed

    Jobski, Kathrin; Behr, Sigrid; Garbe, Edeltraut

    2011-09-01

    Phenprocoumon is the most frequently used vitamin K antagonist in Germany. The aim of this study was to estimate the risk of serious bleeding as a result of the use of drugs with potential interaction with phenprocoumon. We conducted a nested case-control study in a cohort of 246,220 phenprocoumon users in the German Pharmacoepidemiological Research Database. Cases were patients hospitalised for haemorrhage of different kinds. Ten controls were matched to each case by health insurance, birth year and sex using incidence density sampling. Odds ratios (OR) with 95% confidence intervals (CI) of the risk of serious bleeding associated with combined use of phenprocoumon and potentially interacting drugs versus phenprocoumon alone were estimated using conditional logistic regression analysis. Our analyses considered multiple risk factors, such as bleeding history, other comorbidities or co-medication. Our study included 2,553 cases and 25,348 matched controls. An increased risk of bleeding was observed for the combined use of phenprocoumon and clopidogrel vs phenprocoumon use alone (OR: 1.83, 95% CI: 1.41-2.36). Antibiotic drugs associated with an increased risk of haemorrhage in the population of phenprocoumon users included the group of quinolones with ORs ranging from 2.74 (95% CI: 1.80-4.18) for ciprofloxacin to 4.40 (95% CI: 2.45-7.89) for levofloxacin, amoxicillin plus clavulanic acid (OR: 2.99, 95% CI: 1.39-6.42) and cotrimoxazole (OR 3.57, 95% CI: 2.36-5.40). Among non-steroidal anti-inflammatory drugs (NSAIDs), ketoprofen and naproxen were associated with the highest risks. Significantly elevated risks of major bleeding were mainly observed for drugs with known pharmacodynamic interaction with phenprocoumon, and less for drugs with possible pharmacokinetic interaction.

  5. Alcohol drinking and esophageal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population.

    PubMed

    Oze, Isao; Matsuo, Keitaro; Wakai, Kenji; Nagata, Chisato; Mizoue, Tetsuya; Tanaka, Keitaro; Tsuji, Ichiro; Sasazuki, Shizuka; Inoue, Manami; Tsugane, Shoichiro

    2011-05-01

    Although alcohol drinking is considered as an important risk factor for esophageal cancer, the magnitude of the association might be varied among geographic areas. Therefore, we reviewed epidemiologic studies on the association between alcohol drinking and esophageal cancer among the Japanese population. Original data were obtained from MEDLINE, searched using PubMed or from searches of the Ichushi database, complemented with manual searches. Evaluation of associations was based on the strength of evidence ('convincing', 'probable', 'possible' or 'insufficient') and the magnitude of association ('strong', 'moderate', 'weak' or 'no association'), together with biological plausibility as previously evaluated by the International Agency of Research on Cancer. We identified four cohort studies and nine case-control studies. All cohort studies and case-control studies showed strong positive associations between esophageal cancer and alcohol drinking. All cohort studies and six case-control studies showed that alcohol drinking had the dose- or frequency-response relationships with esophageal cancer. In addition, four case-control studies showed that acetaldehyde dehydrogenase Glu504Lys polymorphism had strong effect modification with alcohol drinking. We conclude that there is convincing evidence that alcohol drinking increases the risk of esophageal cancer in the Japanese population.

  6. Risk factors for chronic periodontitis in Sri Lankan adults: a population based case-control study.

    PubMed

    Wellapuli, Nimali; Ekanayake, Lilani

    2017-09-07

    To determine risk factors for chronic periodontitis in 30-60 year olds in Sri Lanka. Cases and controls for this population based unmatched case-control study were identified from a broader cross-sectional study which was conducted to determine the prevalence of chronic periodontitis in 30-60 year old adults in Colombo district Sri Lanka. The study included 694 cases and 706 controls. Data were collected by means of a pre-tested interviewer administered questionnaire to obtain information about socio-demographic and behavioural factors, a physical examination to record anthropometric measurements and an oral examination. Being a male, a Muslim, belonging to the 45-60 year old age group, having less than 12 years of education, using the finger to clean teeth, current smoking, current betel quid chewing, self-reported diabetes and hypertension emerged as risk factors for chronic periodontitis. Several socio-demographic and behavioural factors as well as co-morbid conditions emerged as independent risk factors for chronic periodontits in this population. The findings could be used for planning programmes to reduce the burden of chronic periodontits in Colombo district Sri Lanka.

  7. Childhood Leukemia and 50 Hz Magnetic Fields: Findings from the Italian SETIL Case-Control Study

    PubMed Central

    Salvan, Alberto; Ranucci, Alessandra; Lagorio, Susanna; Magnani, Corrado

    2015-01-01

    We report on an Italian case-control study on childhood leukemia and exposure to extremely low frequency magnetic fields (ELF-MF). Eligible for inclusion were 745 leukemia cases, aged 0–10 years at diagnosis in 1998–2001, and 1475 sex- and age-matched population controls. Parents of 683 cases and 1044 controls (92% vs. 71%) were interviewed. ELF-MF measurements (24–48 h), in the child’s bedroom of the dwelling inhabited one year before diagnosis, were available for 412 cases and 587 controls included in the main conditional regression analyses. The magnetic field induction was 0.04 μT on average (geometric mean), with 0.6% of cases and 1.6% of controls exposed to >0.3 μT. The impact of changes in the statistical model, exposure metric, and data-set restriction criteria was explored via sensitivity analyses. No exposure-disease association was observed in analyses based on continuous exposure, while analyses based on categorical variables were characterized by incoherent exposure-outcome relationships. In conclusion, our results may be affected by several sources of bias and they are noninformative at exposure levels >0.3 μT. Nonetheless, the study may contribute to future meta- or pooled analyses. Furthermore, exposure levels among population controls are useful to estimate attributable risk. PMID:25689995

  8. Occupation and thyroid cancer: a population-based case-control study in Connecticut

    PubMed Central

    Ba, Yue; Huang, Huang; Lerro, Catherine C.; Li, Shuzhen; Zhao, Nan; Li, Anqi; Ma, Shuangge; Udelsman, Robert; Zhang, Yawei

    2016-01-01

    Objective The study aims to explore the associations between various occupations and thyroid cancer risk. Methods A population-based case-control study involving 462 histologically confirmed incident cases and 498 controls was conducted in Connecticut in 2010–2011. Results A significantly increased risk of thyroid cancer, particularly papillary microcarcinoma, was observed for those working as the healthcare practitioners and technical workers, health diagnosing and treating practitioners and registered nurses. Those working in building and grounds cleaning, maintenance occupations, pest control, retail sales, and customer service also had increased risk for papillary thyroid cancer. Subjects who worked as cooks, janitors, cleaners, and customer service representatives were at an increased risk of papillary thyroid cancer with tumor size >1 cm. Conclusions Certain occupations were associated with an increased risk of thyroid cancer, with some tumor size and subtype specificity. PMID:26949881

  9. Population attributable risks of oral cavity cancer to behavioral and medical risk factors in France: results of a large population-based case-control study, the ICARE study.

    PubMed

    Radoï, Loredana; Menvielle, Gwenn; Cyr, Diane; Lapôtre-Ledoux, Bénédicte; Stücker, Isabelle; Luce, Danièle

    2015-10-31

    Population attributable risks (PARs) are useful tool to estimate the burden of risk factors in cancer incidence. Few studies estimated the PARs of oral cavity cancer to tobacco smoking alone, alcohol drinking alone and their joint consumption but none performed analysis stratified by subsite, gender or age. Among the suspected risk factors of oral cavity cancer, only PAR to a family history of head and neck cancer was reported in two studies. The purpose of this study was to estimate in France the PARs of oral cavity cancer to several recognized and suspected risk factors, overall and by subsite, gender and age. We analysed data from 689 oral cavity cancer cases and 3481 controls included in a population-based case-control study, the ICARE study. Unconditional logistic regression models were used to estimate odds ratios (ORs), PARs and 95% confidence intervals (95% CI). The PARs were 0.3% (95% CI -3.9%; +3.9%) for alcohol alone, 12.7% (6.9%-18.0%) for tobacco alone and 69.9% (64.4%-74.7%) for their joint consumption. PAR to combined alcohol and tobacco consumption was 74% (66.5%-79.9%) in men and 45.4% (32.7%-55.6%) in women. Among suspected risk factors, body mass index 2 years before the interview <25 kg.m(-2), never tea drinking and family history of head and neck cancer explained 35.3% (25.7%-43.6%), 30.3% (14.4%-43.3%) and 5.8% (0.6%-10.8%) of cancer burden, respectively. About 93% (88.3%-95.6%) of oral cavity cancers were explained by all risk factors, 94.3% (88.4%-97.2%) in men and only 74.1% (47.0%-87.3%) in women. Our study emphasizes the role of combined tobacco and alcohol consumption in the oral cavity cancer burden in France and gives an indication of the proportion of cases attributable to other risk factors. Most of oral cavity cancers are attributable to concurrent smoking and drinking and would be potentially preventable through smoking or drinking cessation. If the majority of cases are explained by recognized or suspected risk factors in men, a substantial number of cancers in women are probably due to still unexplored factors that remain to be clarified by future studies.

  10. Type, number or both? A population-based matched case-control study on the risk of fall injuries among older people and number of medications beyond fall-inducing drugs.

    PubMed

    Laflamme, Lucie; Monárrez-Espino, Joel; Johnell, Kristina; Elling, Berty; Möller, Jette

    2015-01-01

    Drug use is a modifiable risk factor for fall-related injuries in older people. Whereas the injurious effect of polypharmacy is established, that of low numbers of medications has not been fully ascertained. Neither do we know whether it is the number per se or the type of medications that actually matters. We assessed this question for fall injuries leading to hospitalization. National register-based, population-based, matched case-control study. Community dwellers aged 65+ years living in Sweden between March 2006 and December 2009. Cases (n = 64,399) were identified in the national inpatient register and four controls per case were randomly matched by gender, date of birth and residential area. The association between number of prescribed medications, assessed through linkage with the Swedish prescribed drug register, and the risk of injurious falls was estimated with odds ratios with 95% confidence intervals using conditional logistic regression, adjusted for demographic and health status. The number of medications was associated with an increased risk of fall injury in a dose-response fashion, even after adjustment for marital status, comorbidity and number of fall-risk-inducing drugs (FRIDs). Using ten or more medications was associated with an almost two-fold higher risk (adjusted OR: 1.76, 95% CI: 1.66 to 1.88). When stratified by use (or not) of at least one FRID, the association weakened slightly among both non-users (adjusted OR: 1.50, 95% CI: 1.34 to 1.67) and users (adjusted OR: 1.67, 95% CI: 1.58 to 1.77). In older people, not only large but also small numbers of medications may affect the risk for them to sustain injurious falls. Although the mechanisms lying behind this are complex, the finding challenges the prevention strategies targeting either specific types of medications (FRIDs) or high numbers of them.

  11. European multiple sclerosis risk variants in the south Asian population.

    PubMed

    Pandit, Lekha; Ban, Maria; Beecham, Ashley Harris; McCauley, Jacob L; Sawcer, Stephen; D'Cunha, Anitha; Malli, Chaitra; Malik, Omar

    2016-10-01

    In less than a decade, genomewide association studies have identified over 100 single-nucleotide variants that are associated with increased risk of developing multiple sclerosis. However, since these studies have focused almost exclusively on European populations, it is unclear what role these variants might play in determining risk in other ethnic groups. To assess the effects of European multiple sclerosis-associated risk variants in the south Asian population. Using a combination of chip-based genotyping and next-generation sequencing, we have assessed 109 European-associated variants in a total of 270 cases and 555 controls from the south Asian population. We found that two-thirds of the tested variants (72/109) showed over representation of the European risk allele in south Asian cases (p < 0.0003). In the rest of the Immunochip array, the most associated variant was rs7318477 which maps close to TNFSF13B, the gene for the B-cell-related protein BAFF. Our data indicate substantial overlap in genetic risk architecture between Europeans and south Asians and suggest that the aetiology of the disease may be largely independent of ethnicity. © The Author(s), 2016.

  12. Multicentre hospital-based case-control study of diffuse large B-cell lymphoma in Shanghai, China.

    PubMed

    Fan, Rong; Zhang, Lu-Yao; Wang, Hong; Yang, Bo; Han, Tao; Zhao, Xiao-Li; Wang, Wei; Wang, Xiao-Qin; Lin, Guo-Wei

    2012-01-01

    Several potential risk factors have been identified for diffuse large B-cell lymphoma (DLBCL); however, epidemiological studies investigating the association between these risk factors and DLBCL have yielded inconsistent results. To investigate potential medical, lifestyle, and environmental risk factors of DLBCL in Shanghai, China through a hospital-based case-control study. One-hundred- and-forty-seven newly diagnosed DLBCL patients and 294 sex- and age-matched controls were recruited from 11 hospitals in Shanghai between 2003 and 2007. A standardized structured questionnaire was used to obtain patient data on demographics, medical history, family history, lifestyle, and environmental exposures. Conditional logistic regression models were used to estimate odds ratios (ORs), with 95% confidence intervals (CIs), for risk associated with each data category. History of tuberculosis (TB) infection and "living on a farm" were positively associated with DLBCL (TB: OR=3.05, 95% CI: 1.19-7.80; farm: OR=1.82, 95% CI: 1.21-2.73). In contrast, taking traditional Chinese medicine was negatively associated with DLBCL (OR=0.36, 95% CI: 0.14- 0.89). No significant correlation with DLBCL risk was found for any of the other potential risk factors (p>0.05), including but not limited to hair dyes, alcohol drinking, smoking, and home/workplace renovation within one year. Consistent with results from previous studies in other DLBCL case populations, traditional Chinese medicine appeared to have a direct or indirect protective effect against DLBCL. However, this study also identified a possible predisposition for DLBCL in TB sufferers and farmers.

  13. A community-based, case-control study of childhood stroke risk associated with congenital heart disease

    PubMed Central

    Fox, Christine K.; Sidney, Stephen; Fullerton, Heather J.

    2014-01-01

    Background and Purpose A better understanding of the stroke risk factors in children with congenital heart disease (CHD) could inform stroke prevention strategies. We analyzed pediatric stroke associated with CHD in a large community-based, case-control study. Methods From 2.5 million children (< 20 years) enrolled in a Northern California integrated healthcare plan, we identified ischemic and hemorrhagic strokes and randomly selected age and facility-matched stroke-free controls (3 per case). We determined exposure to CHD (diagnosed prior to stroke) and used conditional logistic regression to analyze stroke risk. Results CHD was identified in 15/412 cases (4%) versus 7/1,236 controls (0.6%). Children (28 days – 20 years) with CHD had 19-fold (Odds Ratio [OR] 19; 95% Confidence Interval [CI] 4.2, 83) increased stroke risk compared to controls. History of CHD surgery was associated with >30-fold increased risk of stroke (OR 31; CI 4, 241 compared to controls). After excluding peri-operative strokes, a history of CHD surgery still increased childhood stroke risk (OR 13; CI 1.5, 114). The majority of children with stroke and CHD were outpatient at the time of stroke, and almost half the cases who underwent cardiac surgery had their stroke >5 years after the most recent procedure. An estimated 7% of ischemic and 2% of hemorrhagic childhood strokes in the population were attributable to CHD. Conclusions CHD is an important childhood stroke risk factor. Children who undergo CHD surgery remain at elevated risk outside of the peri-operative period, and would benefit from optimized long-term stroke prevention strategies. PMID:25516197

  14. Clinically observed chickenpox and the risk of childhood-onset multiple sclerosis.

    PubMed

    Mikaeloff, Yann; Caridade, Guillaume; Suissa, Samy; Tardieu, Marc

    2009-05-15

    The authors conducted a population-based case-control study to investigate whether clinically observed chickenpox, linked with a level of intensity for clinical expression, increases the risk of multiple sclerosis (MS) in childhood. The cases were MS patients whose disease onset occurred between 1994 and 2003, before age 16 years, in France. Each case was matched for age, sex, and geographic origin with as many as 12 controls randomly selected from the general population. Information about clinically observed chickenpox in cases and controls before the index date regarding onset of MS was collected with a standardized questionnaire and was checked against health certificates. Conditional logistic regression was used to estimate the odds ratio for an association between MS and chickenpox. The 137 MS cases were matched with 1,061 controls. Clinically observed chickenpox had occurred in 76.6% of the cases and 84.9% of their matched controls. The adjusted odds ratio of MS onset associated with chickenpox occurrence was 0.58 (95% confidence interval: 0.36, 0.92). The authors concluded that clinically observed chickenpox was associated with a lower risk of childhood-onset MS in a French population.

  15. Chronic Rhinosinusitis Associated with Erectile Dysfunction: A Population-Based Study.

    PubMed

    Tai, Shu-Yu; Wang, Ling-Feng; Tai, Chih-Feng; Huang, Yu-Ting; Chien, Chen-Yu

    2016-08-31

    Few studies have investigated the relationship between chronic rhinosinusitis (CRS) and erectile dysfunction (ED). This case-control study aimed to investigate the association between CRS and the risk of ED in a large national sample. Tapping Taiwan's National Health Insurance Research Database, we identified people 30 years or older with a new primary diagnosis of CRS between 1996 and 2007. The cases were compared with sex- and age-matched controls. We identified 14 039 cases and recruited 140 387 matched controls. Both groups were followed up in the same database until the end of 2007 for instances of ED. Of those with CRS, 294 (2.1%) developed ED during a mean (SD) follow-up of 3.20 (2.33) years, while 1 661 (1.2%) of the matched controls developed ED, mean follow up 2.97 (2.39) years. Cox regression analyses were performed adjusting for sex, age, insurance premium, residence, hypertension, hyperlipidemia, diabetes, obesity, coronary heart disease, chronic kidney disease, chronic obstructive pulmonary disease, asthma, allergic rhinitis, arrhythmia, ischemic stroke, intracerebral hemorrhage, and medications. CRS was revealed to be an independent predictor of ED in the fully adjusted model (HR = 1.51; 95% CI = 1.33-1.73; P < 0.0001).

  16. Fibromyalgia: epidemiology and risk factors, a population-based case-control study in Lebanon.

    PubMed

    Moukaddem, Afaf; Chaaya, Monique; Slim, Zeinab F N; Jaffa, Miran; Sibai, Abla Mehio; Uthman, Imad

    2017-02-01

    To investigate the epidemiology of fibromyalgia (FM) and assess its risk factors. Using data from the 2009 Community Oriented Program for Control of Rheumatic Diseases (COPCORD) study conducted in Lebanon, a population-based case control study was performed. The sample included 34 FM patients, frequency matched with 136 controls free from any musculoskeletal complaints and randomly sampled from the population. The controls were frequency matched with cases by age and gender. The 34 female FM cases were prevalent cases which existed for a long period of time and all those who consulted a doctor were previously misdiagnosed. Family history of joint problems (OR = 4.93, 95% CI: 1.56-15.58) and working status (OR = 2.69, 95% CI: 1.04-6.93) were significant risk factors for FM, after adjusting for body mass index, distress level, smoking status and residence location. This was the first study to address the epidemiology of FM in Lebanon and the region. The chronic nature of FM that is characterized by frequent bouts of intense disabling pain and symptoms constitutes a significant health and economic burden. Clustering of cases in coastal areas was partially explained by other factors such as body mass index, distress level, smoking and work status. The high burden of FM found in our study calls for further investigation of potential risk factors of this condition. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  17. Clostridium difficile in the Military Population

    DTIC Science & Technology

    2016-08-05

    association between race and infection . This is similar to the Buchner and associates case- control study; which noted an increase in occurrence of C...sustained within a hospital , additional persons infected with C. difficile are needed10. Acute appendicitis ranking first among diagnoses for hospitalized ...Buchner AM, Sonnenberg A. Epidemiology of Clostridium difficile infection in a large population of hospitalized US military veterans. Dig Dis Sci

  18. Does cost-effectiveness of influenza vaccine choice vary across the U.S.? An agent-based modeling study.

    PubMed

    DePasse, Jay V; Nowalk, Mary Patricia; Smith, Kenneth J; Raviotta, Jonathan M; Shim, Eunha; Zimmerman, Richard K; Brown, Shawn T

    2017-07-13

    In a prior agent-based modeling study, offering a choice of influenza vaccine type was shown to be cost-effective when the simulated population represented the large, Washington DC metropolitan area. This study calculated the public health impact and cost-effectiveness of the same four strategies: No Choice, Pediatric Choice, Adult Choice, or Choice for Both Age Groups in five United States (U.S.) counties selected to represent extremes in population age distribution. The choice offered was either inactivated influenza vaccine delivered intramuscularly with a needle (IIV-IM) or an age-appropriate needle-sparing vaccine, specifically, the nasal spray (LAIV) or intradermal (IIV-ID) delivery system. Using agent-based modeling, individuals were simulated as they interacted with others, and influenza was tracked as it spread through each population. Influenza vaccination coverage derived from Centers for Disease Control and Prevention (CDC) data, was increased by 6.5% (range 3.25%-11.25%) to reflect the effects of vaccine choice. Assuming moderate influenza infectivity, the number of averted cases was highest for the Choice for Both Age Groups in all five counties despite differing demographic profiles. In a cost-effectiveness analysis, Choice for Both Age Groups was the dominant strategy. Sensitivity analyses varying influenza infectivity, costs, and degrees of vaccine coverage increase due to choice, supported the base case findings. Offering a choice to receive a needle-sparing influenza vaccine has the potential to significantly reduce influenza disease burden and to be cost saving. Consistent findings across diverse populations confirmed these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Automatic initialization and quality control of large-scale cardiac MRI segmentations.

    PubMed

    Albà, Xènia; Lekadir, Karim; Pereañez, Marco; Medrano-Gracia, Pau; Young, Alistair A; Frangi, Alejandro F

    2018-01-01

    Continuous advances in imaging technologies enable ever more comprehensive phenotyping of human anatomy and physiology. Concomitant reduction of imaging costs has resulted in widespread use of imaging in large clinical trials and population imaging studies. Magnetic Resonance Imaging (MRI), in particular, offers one-stop-shop multidimensional biomarkers of cardiovascular physiology and pathology. A wide range of analysis methods offer sophisticated cardiac image assessment and quantification for clinical and research studies. However, most methods have only been evaluated on relatively small databases often not accessible for open and fair benchmarking. Consequently, published performance indices are not directly comparable across studies and their translation and scalability to large clinical trials or population imaging cohorts is uncertain. Most existing techniques still rely on considerable manual intervention for the initialization and quality control of the segmentation process, becoming prohibitive when dealing with thousands of images. The contributions of this paper are three-fold. First, we propose a fully automatic method for initializing cardiac MRI segmentation, by using image features and random forests regression to predict an initial position of the heart and key anatomical landmarks in an MRI volume. In processing a full imaging database, the technique predicts the optimal corrective displacements and positions in relation to the initial rough intersections of the long and short axis images. Second, we introduce for the first time a quality control measure capable of identifying incorrect cardiac segmentations with no visual assessment. The method uses statistical, pattern and fractal descriptors in a random forest classifier to detect failures to be corrected or removed from subsequent statistical analysis. Finally, we validate these new techniques within a full pipeline for cardiac segmentation applicable to large-scale cardiac MRI databases. The results obtained based on over 1200 cases from the Cardiac Atlas Project show the promise of fully automatic initialization and quality control for population studies. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Insurance problems among inflammatory bowel disease patients: results of a Dutch population based study.

    PubMed

    Russel, M G V M; Ryan, B M; Dagnelie, P C; de Rooij, M; Sijbrandij, J; Feleus, A; Hesselink, M; Muris, J W; Stockbrugger, R

    2003-03-01

    The majority of patients with inflammatory bowel disease (IBD) have a normal life expectancy and therefore should not be weighted when applying for life assurance. There is scant literature on this topic. In this study our aim was to document and compare the incidence of difficulties in application for life and medical insurance in a population based cohort of IBD patients and matched population controls. A population based case control study of 1126 IBD patients and 1723 controls. Based on a detailed questionnaire, the frequency and type of difficulties encountered when applying for life and medical insurance in matched IBD and control populations were appraised. In comparison with controls, IBD patients had an 87-fold increased risk of encountering difficulties when applying for life assurance (odds ratio (OR) 87 (95% confidence interval (CI) 31-246)), with a heavily weighted premium being the most common problem. Patients of high educational status, with continuous disease activity, and who smoked had the highest odds of encountering such problems. Medical insurance difficulties were fivefold more common in IBD patients compared with controls (OR 5.4 (95% CI 2.3-13)) although no specific disease or patient characteristics were identified as associated with such difficulties. This is the first detailed case control study that has investigated insurance difficulties among IBD patients. Acquiring life and medical insurance constituted a major problem for IBD patients in this study. These results are likely to be more widely representative given that most insurance companies use international guidelines for risk assessment. In view of the recent advances in therapy and promising survival data on IBD patients, evidence based guidelines for risk assessment of IBD patients by insurance companies should be drawn up to prevent possible discriminatory practices.

  1. Insurance problems among inflammatory bowel disease patients: results of a Dutch population based study

    PubMed Central

    Russel, M G V M; Ryan, B M; Dagnelie, P C; de Rooij, M; Sijbrandij, J; Feleus, A; Hesselink, M; Muris, J W; Stockbrugger, R

    2003-01-01

    Background and aims: The majority of patients with inflammatory bowel disease (IBD) have a normal life expectancy and therefore should not be weighted when applying for life assurance. There is scant literature on this topic. In this study our aim was to document and compare the incidence of difficulties in application for life and medical insurance in a population based cohort of IBD patients and matched population controls. Methods: A population based case control study of 1126 IBD patients and 1723 controls. Based on a detailed questionnaire, the frequency and type of difficulties encountered when applying for life and medical insurance in matched IBD and control populations were appraised. Results: In comparison with controls, IBD patients had an 87-fold increased risk of encountering difficulties when applying for life assurance (odds ratio (OR) 87 (95% confidence interval (CI) 31–246)), with a heavily weighted premium being the most common problem. Patients of high educational status, with continuous disease activity, and who smoked had the highest odds of encountering such problems. Medical insurance difficulties were fivefold more common in IBD patients compared with controls (OR 5.4 (95% CI 2.3–13)) although no specific disease or patient characteristics were identified as associated with such difficulties. Conclusions: This is the first detailed case control study that has investigated insurance difficulties among IBD patients. Acquiring life and medical insurance constituted a major problem for IBD patients in this study. These results are likely to be more widely representative given that most insurance companies use international guidelines for risk assessment. In view of the recent advances in therapy and promising survival data on IBD patients, evidence based guidelines for risk assessment of IBD patients by insurance companies should be drawn up to prevent possible discriminatory practices. PMID:12584216

  2. Learning-by-catching: uncertain invasive-species populations and the value of information.

    PubMed

    D'Evelyn, Sean T; Tarui, Nori; Burnett, Kimberly; Roumasset, James A

    2008-12-01

    This paper develops a model of invasive species control when the species' population size is unknown. In the face of an uncertain population size, a resource manager's species-control efforts provide two potential benefits: (1) a direct benefit of possibly reducing the population of invasive species, and (2) an indirect benefit of information acquisition (due to learning about the population size, which reduces uncertainty). We provide a methodology that takes into account both of these benefits, and show how optimal management decisions are altered in the presence of the indirect benefit of learning. We then apply this methodology to the case of controlling the Brown Treesnake (Boiga irregularis) on the island of Saipan. We find that the indirect benefit--the value of information to reduce uncertainty--is likely to be quite large.

  3. Pest persistence and eradication conditions in a deterministic model for sterile insect release.

    PubMed

    Gordillo, Luis F

    2015-01-01

    The release of sterile insects is an environment friendly pest control method used in integrated pest management programmes. Difference or differential equations based on Knipling's model often provide satisfactory qualitative descriptions of pest populations subject to sterile release at relatively high densities with large mating encounter rates, but fail otherwise. In this paper, I derive and explore numerically deterministic population models that include sterile release together with scarce mating encounters in the particular case of species with long lifespan and multiple matings. The differential equations account separately the effects of mating failure due to sterile male release and the frequency of mating encounters. When insects spatial spread is incorporated through diffusion terms, computations reveal the possibility of steady pest persistence in finite size patches. In the presence of density dependence regulation, it is observed that sterile release might contribute to induce sudden suppression of the pest population.

  4. Health extension workers improve tuberculosis case finding and treatment outcome in Ethiopia: a large-scale implementation study

    PubMed Central

    Datiko, Daniel G; Yassin, Mohammed A; Theobald, Sally J; Blok, Lucie; Suvanand, Sahu; Creswell, Jacob

    2017-01-01

    Background Tuberculosis (TB) is a major cause of death in Ethiopia. One of the main barriers for TB control is the lack of access to health services. Methods We evaluated a diagnostic and treatment service for TB based on the health extension workers (HEW) of the Ethiopian Health Extension Programme in Sidama Zone, with 3.5 million population. We added the services to the HEW routines and evaluated their effect over 4.5 years. 1024 HEWs were trained to identify individuals with symptoms of TB, request sputum samples and prepare smears. Smears were transported to designated laboratories. Individuals with TB were offered treatment at home or the local health post. A second zone (Hadiya) with 1.2 million population was selected as control. We compared TB case notification rates (CNR) and treatment outcomes in the zones 3 years before and 4.5 years after intervention. Results HEWs identified 216 165 individuals with symptoms and 27 918 (12%) were diagnosed with TB. Smear-positive TB CNR increased from 64 (95% CI 62.5 to 65.8) to 127 (95% CI 123.8 to 131.2) and all forms of TB increased from 102 (95% CI 99.1 to 105.8) to 177 (95% CI 172.6 to 181.0) per 100 000 population in the first year of intervention. In subsequent years, the smear-positive CNR declined by 9% per year. There was no change in CNR in the control area. Treatment success increased from 76% before the intervention to 95% during the intervention. Patients lost to follow-up decreased from 21% to 3% (p<0.001). Conclusion A community-based package significantly increased case finding and improved treatment outcome. Implementing this strategy could help meet the Ethiopian Sustainable Development Goal targets. PMID:29209537

  5. Occupational Exposure to Electric Shocks and Magnetic Fields and Amyotrophic Lateral Sclerosis in Sweden.

    PubMed

    Fischer, Heidi; Kheifets, Leeka; Huss, Anke; Peters, Tracy L; Vermeulen, Roel; Ye, Weimin; Fang, Fang; Wiebert, Pernilla; Vergara, Ximena P; Feychting, Maria

    2015-11-01

    Amyotrophic lateral sclerosis (ALS) has been consistently related to "electric occupations," but associations with magnetic field levels were generally weaker than those with electrical occupations. Exposure to electric shock has been suggested as a possible explanation. Furthermore, studies were generally based on mortality or prevalence of ALS, and studies often had limited statistical power. Using two electric shock and three magnetic field job-exposure matrices, we evaluated the relationship of occupational magnetic fields, electric shocks, electric occupations, and incident ALS in a large population-based nested case-control study in Sweden. Subanalyses, specified a priori, were performed for subjects by gender and by age (less than and more than 65 years). Overall, we did not observe any associations between occupational magnetic field or electric shock exposure and ALS. For individuals less than 65 years old, high electric shock exposure was associated with an odds ratio (OR) of 1.22 (95% confidence interval [CI] = 1.03, 1.43). The corresponding result for the age group 65 years or older was OR = 0.92 (95% CI = 0.81, 1.05). Results were similar regardless which job exposure matrices, exposure definitions, or cutpoints were used. For electric occupations, ORs were close to unity, regardless of age. For welders, no association was observed overall, although for welders <65 years the OR was 1.52 (95% CI = 1.05, 2.21). In this very large population-based study based on incident ALS case subjects, we did not confirm previous observations of higher risk of ALS in electrical occupations, and provided only weak support for associations between electric shocks and ALS.

  6. Migraine with aura and risk of silent brain infarcts and white matter hyperintensities: an MRI study

    PubMed Central

    Garde, Ellen; Blaabjerg, Morten; Nielsen, Helle H.; Krøigård, Thomas; Østergaard, Kamilla; Møller, Harald S.; Hjelmborg, Jacob; Madsen, Camilla G.; Iversen, Pernille; Kyvik, Kirsten O.; Siebner, Hartwig R.; Ashina, Messoud

    2016-01-01

    Abstract A small number of population-based studies reported an association between migraine with aura and risk of silent brain infarcts and white matter hyperintensities in females. We investigated these relations in a population-based sample of female twins. We contacted female twins ages 30–60 years identified through the population-based Danish Twin Registry. Based on questionnaire responses, twins were invited to participate in a telephone-based interview conducted by physicians. Headache diagnoses were established according to the International Headache Society criteria. Cases with migraine with aura, their co-twins, and unrelated migraine-free twins (controls) were invited to a brain magnetic resonance imaging scan performed at a single centre. Brain scans were assessed for the presence of infarcts, and white matter hyperintensities (visual rating scales and volumetric analyses) blinded to headache diagnoses. Comparisons were based on 172 cases, 34 co-twins, and 139 control subjects. Compared with control subjects, cases did not differ with regard to frequency of silent brain infarcts (four cases versus one control), periventricular white matter hyperintensity scores [adjusted mean difference (95% confidence interval): −0.1 (−0.5 to 0.2)] or deep white matter hyperintensity scores [adjusted mean difference (95% confidence interval): 0.1 (−0.8 to 1.1)] assessed by Scheltens’ scale. Cases had a slightly higher total white matter hyperintensity volume compared with controls [adjusted mean difference (95% confidence interval): 0.17 (−0.08 to 0.41) cm 3 ] and a similar difference was present in analyses restricted to twin pairs discordant for migraine with aura [adjusted mean difference 0.21 (−0.20 to 0.63)], but these differences did not reach statistical significance. We found no evidence of an association between silent brain infarcts, white matter hyperintensities, and migraine with aura. PMID:27190013

  7. A polygenic burden of rare disruptive mutations in schizophrenia

    PubMed Central

    Purcell, Shaun M.; Moran, Jennifer L.; Fromer, Menachem; Ruderfer, Douglas; Solovieff, Nadia; Roussos, Panos; O’Dushlaine, Colm; Chambert, Kimberly; Bergen, Sarah E.; Kähler, Anna; Duncan, Laramie; Stahl, Eli; Genovese, Giulio; Fernández, Esperanza; Collins, Mark O; Komiyama, Noboru H.; Choudhary, Jyoti S.; Magnusson, Patrik K. E.; Banks, Eric; Shakir, Khalid; Garimella, Kiran; Fennell, Tim; de Pristo, Mark; Grant, Seth G.N.; Haggarty, Stephen; Gabriel, Stacey; Scolnick, Edward M.; Lander, Eric S.; Hultman, Christina; Sullivan, Patrick F.; McCarroll, Steven A.; Sklar, Pamela

    2014-01-01

    By analyzing the exome sequences of 2,536 schizophrenia cases and 2,543 controls, we have demonstrated a polygenic burden primarily arising from rare (<1/10,000), disruptive mutations distributed across many genes. Especially enriched genesets included the voltage-gated calcium ion channel and the signaling complex formed by the activity-regulated cytoskeleton-associated (ARC) scaffold protein of the postsynaptic density (PSD), sets previously implicated by genome-wide association studies (GWAS) and copy-number variation (CNV) studies. Similar to reports in autism, targets of the fragile × mental retardation protein (FMRP, product of FMR1) were enriched for case mutations. No individual gene-based test achieved significance after correction for multiple testing and we did not detect any alleles of moderately low frequency (~0.5-1%) and moderately large effect. Taken together, these data suggest that population-based exome sequencing can discover risk alleles and complements established gene mapping paradigms in neuropsychiatric disease. PMID:24463508

  8. Suicidal drug overdose in patients with systemic lupus erythematosus, a nationwide population-based case-control study.

    PubMed

    Tang, K T; Lin, C H; Chen, H H; Chen, Y H; Chen, D Y

    2016-02-01

    A four-fold increase of suicide mortality has been demonstrated in systemic lupus erythematosus (SLE) patients. Prior studies showed that the most common method of suicide attempts in SLE patients involves drug overdose. Therefore, we conducted a nationwide population-based case-control study to elucidate factors associated with drug overdose as suicide attempt in SLE patients. This study was based on the National Health Insurance Research Database in Taiwan. We identified all SLE patients from January 1, 2000 to December 31, 2010. Patients who had suicidal drug overdose (SDO) were selected as cases while age- and gender-matched patients who did not have SDO were selected as controls. The incidence rate of SDO in SLE patients was 291 cases per 100,000 person-years, higher than that in the general population (160 cases per 100,000 person-years). In a multivariate logistic regression analysis, we observed that SDO was associated with psychiatric disorders such as depressive disorders (odds ratio: 8.36, 95% confidence interval (CI): 5.60-12.48) and insomnia (odds ratio: 2.71, 95% CI: 1.73-4.25), and lower monthly income (odds ratios: 2.74 to 3.50) in SLE patients. SDO is associated with psychiatric disorders such as depressive disorders and insomnia, and lower monthly income in SLE patients. © The Author(s) 2015.

  9. Estimating the Marginal Causal Effect of Fish Consumption during Adolescence on Multiple Sclerosis: A Population-Based Incident Case-Control Study.

    PubMed

    Abdollahpour, Ibrahim; Nedjat, Saharnaz; Mansournia, Mohammad Ali; Sahraian, Mohammad Ali; Kaufman, Jay S

    2018-01-01

    Adolescence is considered as a critical time period in multiple sclerosis (MS) etiology. Nonetheless, there are insufficient reports regarding the potential role of fresh and canned fish consumptions during adolescence in MS etiology. The authors investigated the association between fresh and canned fish consumptions and MS. This was a population-based incident case-control study conducted in Tehran. Cases (n = 547) identified from Iranian Multiple Sclerosis Society between August 7, 2013, and November 17, 2015 were included in the study. Population-based controls (n = 1,057) were recruited by random digit telephone dialing without any matching. Inverse-probability-of-treatment weighing (IPTW) using 2 sets of propensity scores and model-based standardization were used to separately estimate the marginal odds ratio between fresh and canned fish consumptions in adolescence and MS. The marginal OR for fresh fish was 0.72 (95% CI 0.58-0.90; p = 0.005) in both IPTW analyses. Similarly, the marginal OR for canned fish consumption was 0.75 (95% CI 0.60-0.95; p = 0.014).The model-based standardized OR was 0.72 (95% CI 0.58-0.91; p = 0.008) for fresh and 0.73 (95% CI 0.59-0.94; p = 0.006) for canned fish consumption in adolescence. Subject to limitation of case-control studies in interpreting associations causally, this study suggests that both fresh and canned fish consumptions in adolescence can decrease the risk of MS. © 2018 S. Karger AG, Basel.

  10. Gene-Based Genome-Wide Association Analysis in European and Asian Populations Identified Novel Genes for Rheumatoid Arthritis.

    PubMed

    Zhu, Hong; Xia, Wei; Mo, Xing-Bo; Lin, Xiang; Qiu, Ying-Hua; Yi, Neng-Jun; Zhang, Yong-Hong; Deng, Fei-Yan; Lei, Shu-Feng

    2016-01-01

    Rheumatoid arthritis (RA) is a complex autoimmune disease. Using a gene-based association research strategy, the present study aims to detect unknown susceptibility to RA and to address the ethnic differences in genetic susceptibility to RA between European and Asian populations. Gene-based association analyses were performed with KGG 2.5 by using publicly available large RA datasets (14,361 RA cases and 43,923 controls of European subjects, 4,873 RA cases and 17,642 controls of Asian Subjects). For the newly identified RA-associated genes, gene set enrichment analyses and protein-protein interactions analyses were carried out with DAVID and STRING version 10.0, respectively. Differential expression verification was conducted using 4 GEO datasets. The expression levels of three selected 'highly verified' genes were measured by ELISA among our in-house RA cases and controls. A total of 221 RA-associated genes were newly identified by gene-based association study, including 71'overlapped', 76 'European-specific' and 74 'Asian-specific' genes. Among them, 105 genes had significant differential expressions between RA patients and health controls at least in one dataset, especially for 20 genes including 11 'overlapped' (ABCF1, FLOT1, HLA-F, IER3, TUBB, ZKSCAN4, BTN3A3, HSP90AB1, CUTA, BRD2, HLA-DMA), 5 'European-specific' (PHTF1, RPS18, BAK1, TNFRSF14, SUOX) and 4 'Asian-specific' (RNASET2, HFE, BTN2A2, MAPK13) genes whose differential expressions were significant at least in three datasets. The protein expressions of two selected genes FLOT1 (P value = 1.70E-02) and HLA-DMA (P value = 4.70E-02) in plasma were significantly different in our in-house samples. Our study identified 221 novel RA-associated genes and especially highlighted the importance of 20 candidate genes on RA. The results addressed ethnic genetic background differences for RA susceptibility between European and Asian populations and detected a long list of overlapped or ethnic specific RA genes. The study not only greatly increases our understanding of genetic susceptibility to RA, but also provides important insights into the ethno-genetic homogeneity and heterogeneity of RA in both ethnicities.

  11. Argentine Population Genetic Structure: Large Variance in Amerindian Contribution

    PubMed Central

    Seldin, Michael F.; Tian, Chao; Shigeta, Russell; Scherbarth, Hugo R.; Silva, Gabriel; Belmont, John W.; Kittles, Rick; Gamron, Susana; Allevi, Alberto; Palatnik, Simon A.; Alvarellos, Alejandro; Paira, Sergio; Caprarulo, Cesar; Guillerón, Carolina; Catoggio, Luis J.; Prigione, Cristina; Berbotto, Guillermo A.; García, Mercedes A.; Perandones, Carlos E.; Pons-Estel, Bernardo A.; Alarcon-Riquelme, Marta E.

    2011-01-01

    Argentine population genetic structure was examined using a set of 78 ancestry informative markers (AIMs) to assess the contributions of European, Amerindian, and African ancestry in 94 individuals members of this population. Using the Bayesian clustering algorithm STRUCTURE, the mean European contribution was 78%, the Amerindian contribution was 19.4%, and the African contribution was 2.5%. Similar results were found using weighted least mean square method: European, 80.2%; Amerindian, 18.1%; and African, 1.7%. Consistent with previous studies the current results showed very few individuals (four of 94) with greater than 10% African admixture. Notably, when individual admixture was examined, the Amerindian and European admixture showed a very large variance and individual Amerindian contribution ranged from 1.5 to 84.5% in the 94 individual Argentine subjects. These results indicate that admixture must be considered when clinical epidemiology or case control genetic analyses are studied in this population. Moreover, the current study provides a set of informative SNPs that can be used to ascertain or control for this potentially hidden stratification. In addition, the large variance in admixture proportions in individual Argentine subjects shown by this study suggests that this population is appropriate for future admixture mapping studies. PMID:17177183

  12. Association between allergies, asthma, and breast cancer risk among women in Ontario, Canada.

    PubMed

    Lowcock, Elizabeth C; Cotterchio, Michelle; Ahmad, Noor

    2013-05-01

    To investigate the association between allergies, asthma, and breast cancer risk in a large, population-based case-control study. Breast cancer cases (n = 3,101) were identified using the Ontario Cancer Registry and population controls (n = 3,471) through random digit dialing. Self-reported histories of allergies, hay fever, and asthma were collected by questionnaire. Logistic regression was used to assess associations between breast cancer risk and history of allergy/hay fever and asthma, with 16 possible confounders examined. Analyses were stratified by menopausal status. A history of allergies or hay fever was associated with a small reduction in breast cancer risk [age-adjusted odds ratio (AOR) = 0.86, 95 % confidence interval (CI) 0.77-0.96] and did not differ by menopausal status. Asthma was not associated with breast cancer risk overall; however, among premenopausal women, asthma was associated with a reduced risk of breast cancer (AOR = 0.72, 95 % CI 0.54-0.97). A history of allergies may be associated with a modest reduction in breast cancer risk. Asthma does not appear to be associated with breast cancer risk overall; however, asthma may be associated with reduced breast cancer risk among premenopausal women.

  13. Quantifying penetrance in a dominant disease gene using large population control cohorts

    PubMed Central

    Minikel, Eric Vallabh; Vallabh, Sonia M.; Lek, Monkol; Estrada, Karol; Samocha, Kaitlin E.; Sathirapongsasuti, J. Fah; McLean, Cory Y.; Tung, Joyce Y.; Yu, Linda P.C.; Gambetti, Pierluigi; Blevins, Janis; Zhang, Shulin; Cohen, Yvonne; Chen, Wei; Yamada, Masahito; Hamaguchi, Tsuyoshi; Sanjo, Nobuo; Mizusawa, Hidehiro; Nakamura, Yosikazu; Kitamoto, Tetsuyuki; Collins, Steven J.; Boyd, Alison; Will, Robert G.; Knight, Richard; Ponto, Claudia; Zerr, Inga; Kraus, Theo F.J.; Eigenbrod, Sabina; Giese, Armin; Calero, Miguel; de Pedro-Cuesta, Jesús; Haïk, Stéphane; Laplanche, Jean-Louis; Bouaziz-Amar, Elodie; Brandel, Jean-Philippe; Capellari, Sabina; Parchi, Piero; Poleggi, Anna; Ladogana, Anna; O'Donnell-Luria, Anne H.; Karczewski, Konrad J.; Marshall, Jamie L.; Boehnke, Michael; Laakso, Markku; Mohlke, Karen L.; Kähler, Anna; Chambert, Kimberly; McCarroll, Steven; Sullivan, Patrick F.; Hultman, Christina M.; Purcell, Shaun M.; Sklar, Pamela; van der Lee, Sven J.; Rozemuller, Annemieke; Jansen, Casper; Hofman, Albert; Kraaij, Robert; van Rooij, Jeroen G.J.; Ikram, M. Arfan; Uitterlinden, André G.; van Duijn, Cornelia M.; Daly, Mark J.; MacArthur, Daniel G.

    2016-01-01

    More than 100,000 genetic variants are reported to cause Mendelian disease in humans, but the penetrance - the probability that a carrier of the purported disease-causing genotype will indeed develop the disease - is generally unknown. Here we assess the impact of variants in the prion protein gene (PRNP) on the risk of prion disease by analyzing 16,025 prion disease cases, 60,706 population control exomes, and 531,575 individuals genotyped by 23andMe, Inc. We show that missense variants in PRNP previously reported to be pathogenic are at least 30× more common in the population than expected based on genetic prion disease prevalence. While some of this excess can be attributed to benign variants falsely assigned as pathogenic, other variants have genuine effects on disease susceptibility but confer lifetime risks ranging from <0.1% to ~100%. We also show that truncating variants in PRNP have position-dependent effects, with true loss-of-function alleles found in healthy older individuals, supporting the safety of therapeutic suppression of prion protein expression. PMID:26791950

  14. [Epidemiological methods used in studies in the prevalence of Tourette syndrome].

    PubMed

    Stefanoff, Paweł; Mazurek, Jacek

    2003-01-01

    Tourette syndrome (TS) prevalence was studied since the early 80-ies. Its clinical course is characterised by co-occurrence of motor and vocal tics. Results of previous epidemiological studies were surprisingly divergent: the prevalence varied from 0.5 to 115 cases per 10,000 population. The disease previously recognised as extremely rare and severe is now considered as quite common, with often moderate course. Selected methods used in studies of TS prevalence and analysis of their possible impact on study results are presented. The studies were divided into 3 groups: studies of the hospitalised population, large-scale screenings and studies involving school population, basing on characteristic and size of population, methods of selection of subjects, diagnostic and screening methods used. Studies of the hospitalised population involved patients with most severe symptoms, in different age groups, different methods of final diagnosis confirmation were used. TS prevalence varied from 0.5 up to 15 cases per 10,000 population. Procedures used in large-scale screening studies made possible the elimination of potential selection bias. Large populations were studied using transparent and repetitive confirmation of diagnoses. Their validity was additionally checked in parallel validity studies. TS prevalence was in the range 4.3 to 10 cases per 10,000 population. The highest TS prevalence was obtained in studies involving schoolchildren. Data were gathered from multiple sources: from parents, teachers and children, as well as from classroom observation. Diagnoses were made by experienced clinicians. TS prevalence obtained in school population studies was between 36.2 up to 115 per 10,000 population.

  15. Cigarette smoking and risk of pancreatic cancer: a clinic-based case-control study in the San Francisco Bay Area.

    PubMed

    Lea, C Suzanne; Holly, Elizabeth A; Bracci, Paige M

    2015-11-01

    Cigarette smoking is an established risk factor for pancreatic cancer (PC). We examined the association between cigarette smoking and PC in a San Francisco Bay Area clinic-based, case-control study. A total of 536 cases and sex and age frequency-matched controls (n = 869) were recruited predominately from the University of California San Francisco (UCSF) medical clinics between 2006 and 2011. Participants were interviewed in-person using structured questionnaires. Adjusted odds ratios (ORs) were computed. Forty-eight percent of cases and controls reported never having smoked cigarettes; 39% of cases and 40% of controls were former smokers; 13% of cases and 12% of controls were current smokers. No association was found for either former (OR = 0.85, 95% confidence interval [CI] = 0.66-1.1) or current cigarette smoking (men: OR = 1.0, 95% CI = 0.60-1.7; women: OR = 1.2, 95% CI = 0.73-2.1). No dose-response relationships were detected with number of cigarettes/day, smoking intensity, duration, or years since last smoked. Comparisons with a 1995-1999 population-based UCSF study demonstrated a significantly increased proportion of never smokers in this study (P < .001). This study revealed no significant associations between cigarette smoking and PC in the San Francisco Bay Area during 2006-2011. Data suggest a reduction in the duration of smoking within the referral population. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Appendectomy and Risk of Subsequent Diverticular Disease Requiring Hospitalization: A Population-Based Case-Control Study.

    PubMed

    Sköldberg, Filip; Olén, Ola; Ekbom, Anders; Schmidt, Peter T

    2018-07-01

    Appendicitis and acute diverticulitis share clinical features and are both influenced by genetic and environmental factors. Appendectomy has been positively associated with diverticular disease in hospital-based case-control studies. The aim of the present study was to investigate, in a population-based setting, whether appendectomy, with or without appendicitis, is associated with an altered risk of hospitalization with diverticular disease. This was a population-based case-control study. The study was based on national healthcare and population registers. We studied 41,988 individuals hospitalized between 2000 and 2010 with a first-time diagnosis of colonic diverticular disease and 413,115 matched control subjects. The association between appendectomy with or without appendicitis and diverticular disease was investigated by conditional logistic regression, including a model adjusting for hospital use. A total of 2813 cases (6.7%) and 19,037 controls (4.6%) had a previous record of appendectomy (appendectomy with acute appendicitis: adjusted OR = 1.31 (95% CI, 1.24-1.39); without appendicitis: adjusted OR = 1.30 (95% CI, 1.23-1.38)). Appendectomy was most strongly associated with an increased risk of diverticular disease within 1 year (with appendicitis: adjusted OR = 2.26 (95% CI, 1.61-3.16); without appendicitis: adjusted OR = 3.98 (95% CI, 2.71-5.83)), but the association was still present ≥20 years after appendectomy (with appendicitis: adjusted OR = 1.22 (95% CI, 1.12-1.32); without appendicitis: adjusted OR = 1.19 (95% CI, 1.10-1.28)). Detailed clinical information on the cases was not available. There were unmeasured potential confounders, such as smoking and dietary factors. The findings are consistent with a hypothesis of appendectomy causing an increased risk of diverticular disease, for example, by affecting the mucosal immune system or the gut microbiome. However, several other mechanisms may contribute to, or account for, the positive association, including a propensity for abdominal pain increasing the risk of both the exposure and the outcome. See Video Abstract at http://links.lww.com/DCR/A604.

  17. Sex ratio of congenital abnormalities in the function of maternal age: a population-based study.

    PubMed

    Csermely, Gyula; Urbán, Robert; Czeizel, Andrew E; Veszprémi, Béla

    2015-05-01

    Maternal age effect is well-known in the origin of numerical chromosomal aberrations and some isolated congenital abnormalities (CAs). The sex ratio (SR), i.e. number of males divided by the number of males and females together, of most CAs deviates from the SR of newborn population (0.51). The objective of this analysis was to evaluate the possible association of maternal age with the SR of isolated CAs in a population-based large dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. First, SR of 24 CA entities/groups was estimated in 21,494 patients with isolated CA. In the next step SR of different maternal age groups was compared to the mean SR of the given CA-groups. The SR of four CA-groups showed some deviation in certain maternal age groups. Cases with anencephaly had female excess in young mothers (<25 years). Cases with skull's CAs particularly craniosynostosis had a male excess in cases born to women over 30 years. Two other CA groups (cleft lip ± palate and valvar pulmonic stenosis within the group of right-sided obstructive defect of heart) had significant deviation in SR of certain maternal age groups from the mean SR, but these deviations were not harmonized with joining age groups and thus were considered as a chance effect due to multiple testing. In conclusion, our study did not suggest that in general SR of isolated CAs might be modified by certain maternal age groups with some exception such as anencephaly and craniosynostosis. © 2014 Japanese Teratology Society.

  18. Occupation and bladder cancer: a population-based, case-control study in Iowa.

    PubMed

    Zheng, Tongzhang; Cantor, Kenneth P; Zhang, Yawei; Lynch, Charles F

    2002-07-01

    While considerable efforts have been made to investigate the role of occupation and industry in the risk of bladder cancer, many reported associations have not been consistent, and strong evidence of increased risk is apparent for few occupational groups. To further examine the issue, a large, population-based, case-control study was conducted in the state of Iowa among both men and women. A total of 1452 incident bladder cancer cases and 2434 controls were included in the study. Occupational history was collected from respondents for each job held for 5 years or longer since age 16. Among men, excess risk was observed for industries including plumbing, heating, and air conditioning (odds ratio [OR], = 2.2; 95% confidence interval [CI], 1.0 to 5.0); rubber and plastic products (OR = 3.1; 95% CI, 1.2 to 8.5), motor vehicle parts and supplies (OR = 4.5; 95% CI, 1.2 to 16.5), and occupations including supervisors for transportation and material moving (OR = 6.5; 95% CI, 1.4 to 29.9), material-moving-equipment operators (OR = 1.9; 95% CI, 1.0 to 3.6), automobile mechanics (OR = 1.6; 95% CI, 1.0 to 2.6), painters (OR = 2.7; 95% CI, 1.0 to 7.7), and metal- and plastic-working machine operators (OR = 2.0; 95% CI, 1.1 to 3.4). Among women, significant excess risk was observed for secondary school teachers and record clerks. Housekeepers and butlers and workers in laundering and dry cleaning were also at increased risk. In conclusion, these results suggest that occupational exposures may play a significant role in the risk of bladder cancer.

  19. Maternal occupational exposure to polycyclic aromatic hydrocarbons and congenital heart defects among offspring in the national birth defects prevention study.

    PubMed

    Lupo, Philip J; Symanski, Elaine; Langlois, Peter H; Lawson, Christina C; Malik, Sadia; Gilboa, Suzanne M; Lee, Laura J; Agopian, A J; Desrosiers, Tania A; Waters, Martha A; Romitti, Paul A; Correa, Adolfo; Shaw, Gary M; Mitchell, Laura E

    2012-11-01

    There is evidence in experimental model systems that exposure to polycyclic aromatic hydrocarbons (PAHs) results in congenital heart defects (CHDs); however, to our knowledge, this relationship has not been examined in humans. Therefore, we conducted a case-control study assessing the association between estimated maternal occupational exposure to PAHs and CHDs in offspring. Data on CHD cases and control infants were obtained from the National Birth Defects Prevention Study for the period of 1997 to 2002. Exposure to PAHs was assigned by industrial hygienist consensus, based on self-reported maternal occupational histories from 1 month before conception through the third month of pregnancy. Logistic regression was used to evaluate the association between maternal occupational PAH exposure and specific CHD phenotypic subtypes among offspring. The prevalence of occupational PAH exposure was 4.0% in CHD case mothers (76/1907) and 3.6% in control mothers (104/2853). After adjusting for maternal age, race or ethnicity, education, smoking, folic acid supplementation, and study center, exposure was not associated with conotruncal defects (adjusted odds ratio [AOR], 0.98; 95% confidence interval [CI], 0.58-1.67), septal defects (AOR, 1.28; 95% CI, 0.86-1.90), or with any isolated CHD subtype. Our findings do not support an association between potential maternal occupational exposure to PAHs and various CHDs in a large, population-based study. For CHD phenotypic subtypes in which modest nonsignificant associations were observed, future investigations could be improved by studying populations with a higher prevalence of PAH exposure and by incorporating information on maternal and fetal genotypes related to PAH metabolism. Birth Defects Research (Part A), 2012. Copyright © 2012 Wiley Periodicals, Inc.

  20. Cardiovascular disease and risk of acute pancreatitis in a population-based study.

    PubMed

    Bexelius, Tomas Sjöberg; Ljung, Rickard; Mattsson, Fredrik; Lagergren, Jesper

    2013-08-01

    The low-grade inflammation that characterizes cardiovascular disorders may facilitate the development of pancreatitis; therefore, we investigated the connection between cardiovascular disorders and acute pancreatitis. A nested population-based case-control study was conducted in Sweden in 2006-2008. Cases had a first episode of acute pancreatitis diagnosed in the nationwide Patient Register. Controls were matched on age, sex, and calendar year and randomly selected from all Swedish residents (40-84 years old). Exposure to cardiovascular diseases (hypertension, ischemic heart disease, congestive heart failure, and stroke) was identified in the Patient Register. Relative risk of acute pancreatitis was estimated by odds ratios with 95% confidence intervals using logistic regression adjusting for confounders (matching variables, alcohol disease, chronic obstructive pulmonary disease, type 2 diabetes, number of distinct medications, and other cardiovascular diseases). The study included 6161 cases and 61,637 control subjects. Cardiovascular disorders were positively associated with acute pancreatitis (adjusted odds ratio, 1.35; 95% confidence interval, 1.25-1.45). This population-based study indicates an association between cardiovascular disease and acute pancreatitis. Specifically, ischemic heart disease and hypertension seem to increase the risk of acute pancreatitis. Further research is needed to determine causality.

  1. Proton pump inhibitor and histamine-2 receptor antagonist use and risk of liver cancer in two population-based studies.

    PubMed

    Tran, K T; McMenamin, Ú C; Hicks, B; Murchie, P; Thrift, A P; Coleman, H G; Iversen, L; Johnston, B T; Lee, A J; Cardwell, C R

    2018-05-09

    Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly used. PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans. To investigate PPIs and H2RAs and risk of primary liver cancer in two large independent study populations. We conducted a nested case-control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations with prescribed PPIs and H2RAs were calculated using conditional logistic regression. We also conducted a prospective cohort study within the UK Biobank using self-reported medication use and cancer-registry recorded primary liver cancer. Hazard ratios (HRs) and 95% CIs were calculated using Cox regression. In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2103 controls. In the UK Biobank cohort, 182 of 475 768 participants developed liver cancer. In both, ever use of PPIs was associated with increased liver cancer risk (adjusted OR 1.80, 95% CI 1.34, 2.41 and adjusted HR 1.99, 95% CI 1.34, 2.94 respectively). There was little evidence of association with H2RA use (adjusted OR 1.21, 95% CI 0.84, 1.76 and adjusted HR 1.70, 95% CI 0.82, 3.53 respectively). We found some evidence that PPI use was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research. © 2018 John Wiley & Sons Ltd.

  2. Impact of aggregating exposure information from cases and controls when building a population-based job-exposure matrix from past expert evaluations.

    PubMed

    Kirkham, Tracy L; Siemiatycki, Jack; Labrèche, France; Lavoué, Jérôme

    2016-07-01

    To assess whether the inclusion of data from cases would bias a job-exposure matrix (JEM), we evaluated whether exposures were systematically different between cases and controls from a large historical case-control study. Data included 10 381 jobs assessed for occupational exposure to 294 agents within a lung cancer case-control study. For each sex, 1 JEM was developed from case jobs, and 1 from control jobs: with occupation (four-digit occupational codes), time period (1945-1959, 1960-1984, 1985-1995) and agent axes. We estimated concordance in exposure status (defined as probability of exposure threshold ≥5%) and exposure metrics of probability and intensity of exposure, between the 2 JEMs. Of all hypothetical occupation-period-agent combinations, most had no or few observations. Among males there were 8136 common cells (24-occupational codes, 3-periods, 226-agents), containing sufficient observations for comparison with 92% concordance in exposure status; discordance was equally likely to be towards cases or controls. Females had 1710 common cells (9-occupational codes, 3-periods, 114-agents) with 93% concordance in exposure status; discordant cells were more likely to reflect greater exposure among cases. Among concordantly exposed cells, probability and intensity of exposures were highly correlated between the case JEM and control JEM (Kendall τ>0.50), and absolute differences were small (median difference in probability <1.5%, median ratio in intensity=1.00) for both sexes. Agreement between the case JEM and control JEM was high, suggesting that aggregating the case and control information in our study into a single JEM is justifiable given the benefits of increased sample size. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  3. Association of Asthma with Rheumatoid Arthritis: A Population-Based Case-Control Study.

    PubMed

    Sheen, Youn Ho; Rolfes, Mary C; Wi, Chung-Il; Crowson, Cindy S; Pendegraft, Richard S; King, Katherine S; Ryu, Euijung; Juhn, Young J

    T H 1 and T H 2 cells have counterregulatory relationships. However, the relationship between asthma, a T H 2-predominant condition, and risk of systemic inflammatory diseases such as rheumatoid arthritis (RA), a T H 1 condition, is poorly understood. We aimed to determine whether asthma was associated with increased risks of incident RA among adults. We conducted a retrospective population-based case-control study that examined existing incident RA cases and controls matched by age, sex, and registration year from the general population in Olmsted County, Minnesota, between January 2002 and December 2007. We performed comprehensive medical record reviews to ascertain asthma status using predetermined asthma criteria. The frequency of a history of asthma before the index date was compared between cases and controls. Logistic regression models were used to adjust for confounding factors. We enrolled 221 RA cases and 218 controls. Of the 221 RA cases, 156 (70.6%) were females, 207 (93.7%) were white, the median age at the index date was 52.5 years, and 53 (24.0%) had a history of asthma. Controls had similar characteristics except that 35 of 218 controls (16.1%) had a history of asthma. After adjustment for sex, age, smoking, body mass index, socioeconomic status, and comorbidity, asthma was significantly associated with increased risks of RA (adjusted odds ratio, 1.74; 95% CI, 1.05-2.90; P = .03). Despite the counterregulatory relationship between T H 1 and T H 2 cells, patients with asthma had a significantly higher risk of developing RA than healthy individuals. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  4. Parental and comorbid epilepsy in persons with bipolar disorder.

    PubMed

    Sucksdorff, Dan; Brown, Alan S; Chudal, Roshan; Jokiranta-Olkoniemi, Elina; Leivonen, Susanna; Suominen, Auli; Heinimaa, Markus; Sourander, Andre

    2015-12-01

    Population-based studies have demonstrated an overrepresentation of bipolar disorder (BPD) in individuals with epilepsy. However, few studies have examined the reverse association, i.e. comorbid epilepsy in individuals selected based on BPD diagnosis. No previous population-based study having examined the co-occurrence of BPD and epilepsy has adjusted for parental psychopathology. Such an adjustment is motivated by population-based studies reporting an overrepresentation of various types of parental psychiatric disorders in both BPD and epilepsy. Furthermore, an association between epilepsy in first-degree relatives and BPD has previously only been examined and demonstrated in a small clinical sample. The objective of this study is to examine the associations between parental and comorbid epilepsy and BPD, adjusting for parental psychopathology. This nested case-control study identified 1861 cases with BPD, age up to 25 years, 3643 matched controls, and their parents from Finnish national registers. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) and two-sided significance limits of p<0.05. BPD was associated with comorbid epilepsy (adjusted OR 2.53, 95% CI: 1.73-3.70) but not with parental epilepsy. Epilepsy was found in 3.33% of cases versus 1.29% of controls, 2.69% of cases' parents versus 2.53% of controls' parents. The diagnoses were register-based, not based on standardized procedures with direct ascertainment. An association between BPD and comorbid epilepsy persists even after adjusting for parental psychopathology. Lack of familial clustering of BPD and epilepsy would suggest that the elevated co-occurrence of these disorders is influenced by non-genetic factors. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Birth order and risk of hepatocellular carcinoma in chronic carriers of hepatitis B virus: a case-control study in The Gambia.

    PubMed

    Shimakawa, Yusuke; Lemoine, Maud; Bottomley, Christian; Njai, Harr Freeya; Ndow, Gibril; Jatta, Abdoulie; Tamba, Saydiba; Bojang, Lamin; Taal, Makie; Nyan, Ousman; D'Alessandro, Umberto; Njie, Ramou; Thursz, Mark; Hall, Andrew J

    2015-10-01

    Early age at infection with Hepatitis B virus (HBV) increases the risk of chronic infection. Moreover, early HBV infection may further independently increase the risk of hepatocellular carcinoma (HCC) beyond its effect on chronicity. The distribution of birth order, a proxy for mode and timing of HBV transmission, was compared in The Gambia between hepatitis B surface antigen (HBsAg)-positive HCC cases recruited from hospitals (n = 72) and two HBsAg-positive control groups without HCC: population-based controls from a community HBV screening (n = 392) and hospital-based controls (n = 63). HCC risk decreased with increasing birth order in the population-based case-control analysis. Using first birth order as the reference, the odds ratios were 0.52 (95% CI: 0.20-1.36), 0.52 (0.17-1.56), 0.57 (0.16-2.05) and 0.14 (0.03-0.64) for second, third, fourth and greater than fourth birth order respectively (P = 0.01). A similar inverse association was observed in the hospital-based case-control comparison (P = 0.04). Compared to controls, HCC cases had earlier birth order, a proxy for young maternal age and maternal HBV viraemia at birth. This finding suggests that in chronic HBV carriers perinatal mother-to-infant transmission may increase HCC risk more than horizontal transmission. Providing HBV vaccine within 24 h of birth to interrupt perinatal transmission might reduce the incidence of HCC in The Gambia. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Childhood infectious diseases and risk of leukaemia in an adult population.

    PubMed

    Parodi, Stefano; Crosignani, Paolo; Miligi, Lucia; Nanni, Oriana; Ramazzotti, Valerio; Rodella, Stefania; Costantini, Adele Seniori; Tumino, Rosario; Vindigni, Carla; Vineis, Paolo; Stagnaro, Emanuele

    2013-10-15

    Our study is aimed at investigating the association between common childhood infectious diseases (measles, chickenpox, rubella, mumps and pertussis) and the risk of developing leukaemia in an adult population. A reanalysis of a large population-based case-control study was carried out. Original data included 1,771 controls and 649 leukaemia cases from 11 Italian areas. To contain recall bias, the analysis was restricted to subjects directly interviewed and with a good quality interview (1,165 controls and 312 cases). Odds ratios (ORs) and their related 95% confidence intervals (95% CIs) were estimated by unconditional polychotomous logistic regression model adjusting for age, gender and occupational and lifestyle exposures. A protective effect of at least one infection (OR = 0.66, 95% CI: 0.45-0.97), measles (OR = 0.57, 95% CI: 0.39-0.82) and pertussis (OR = 0.66, 95% CI: 0.45-0.98) was observed for chronic lymphoid leukaemia (CLL). The number of infections was strongly inversely associated with the risk of CLL (p = 0.002, test for trend). With regard to the other types of leukaemia, only a protective effect of pertussis was observed for AML (OR = 0.52, 95% CI: 0.32-0.87). Our results pointed out a protective role of childhood infectious diseases on the risk of CLL in adults. Although a specific antioncogenic effect of some infectious disease, especially measles, cannot be ruled out, the observed decrease of risk with increasing number of infections suggests that a more general "hygiene hypothesis" could be the most likely explanation of the detected association. The protective role of pertussis remains to be elucidated. Copyright © 2013 UICC.

  7. Polymorphisms in CARS are associated with gastric cancer risk: a two-stage case-control study in the Chinese population.

    PubMed

    Tian, Tian; Xiao, Ling; Du, Jiangbo; Zhu, Xun; Gu, Yayun; Qin, Na; Yan, Caiwang; Liu, Li; Ma, Hongxia; Jiang, Yue; Chen, Jiaping; Yu, Hao; Dai, Juncheng

    2017-11-01

    The cysteinyl transfer RNA synthetase gene (CARS) is located on chromosome band 11p15.5, which is an important tumor-suppressor gene region. Mutations in CARS have been identified in many kinds of cancers; however, evidence for a relationship between genetic variants in CARS and gastric cancer at the population level is still lacking. Thus, we explored the association of variants in CARS with gastric cancer using a two-stage case-control strategy in Chinese. We undertook a two-stage case-control study to investigate the association between polymorphisms in CARS and risk of gastric cancer with use of an Illumina Infinium ® BeadChip and an ABI 7900 system. Four single nucleotide polymorphisms (SNPs) were significantly associated with gastric cancer risk in both the discovery stage and the validation stage after adjustment for age and sex. In addition, the combined results of the two stages showed these SNPs were related to gastric cancer risk (P false discovery rate  ≤ 0.001 for rs384,490, rs729662, rs2071101, and rs7394702). In silico analyses revealed that rs384490 and rs7394702 could affect transcription factor response elements or DNA methylation of CARS, and rs729662 was associated with the prognosis of gastric cancer. Additionally, expression quantitative trait loci analysis showed rs384490 and rs729662 might alter expression of CARS-related genes. The potential functional SNPs in CARS might influence the biological functions of CARS or CARS-related genes and ultimately modify the occurrence and development of gastric cancer in Chinese. Further large-scale population-based studies or biological functional assays are warranted to validate our findings.

  8. Phthalates and risk of endometriosis

    PubMed Central

    Upson, Kristen; Sathyanarayana, Sheela; De Roos, Anneclaire J.; Thompson, Mary Lou; Scholes, Delia; Dills, Russell; Holt, Victoria L.

    2013-01-01

    Background Phthalates are ubiquitous environmental chemicals with endocrine disruptive properties. The impact of these chemicals on endocrine-related disease in reproductive-age women is not well understood. Objective To investigate the relationship between urinary phthalate metabolite concentrations and the risk of a hormonally-driven disease, endometriosis, in reproductive-age women. Methods We used data from a population-based case-control study of endometriosis, conducted among female enrollees of a large healthcare system in the U.S. Pacific Northwest. We measured urinary phthalate metabolite concentrations on incident, surgically-confirmed cases (n=92) diagnosed between 1996 and 2001 and population-based controls (n=195). Odds ratios (OR), and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusting for urinary creatinine concentrations, age, and reference year. Results The majority of women in our study had detectable concentrations of phthalate metabolites. We observed a strong inverse association between urinary mono-(2-ethyl-5-hexyl) phthalate (MEHP) concentration and endometriosis risk, particularly when comparing the fourth and first MEHP quartiles (aOR 0.3, 95% CI: 0.1–0.7). Our data suggested an inverse association between endometriosis and urinary concentrations of other di-2-ethylhexyl phthalate (DEHP) metabolites (mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)) and ΣDEHP, however, the confidence intervals include the null. Our data also suggested increased endometriosis risk with greater urinary concentrations of mono-benzyl phthalate (MBzP) and mono-ethyl phthalate (MEP), although the associations were not statistically significant. Conclusions Exposure to select phthalates is ubiquitous among female enrollees of a large healthcare system in the U.S. Pacific Northwest. The findings from our study suggest that phthalates may alter the risk of a hormonally-mediated disease among reproductive-age women. PMID:23890968

  9. Environmental Tobacco Smoke and Adult-Onset Asthma: A Population-Based Incident Case–Control Study

    PubMed Central

    Jaakkola, Maritta S.; Piipari, Ritva; Jaakkola, Niina; Jaakkola, Jouni J. K.

    2003-01-01

    Objectives. The authors assessed the effects of environmental tobacco smoke (ETS) on the development of asthma in adults. Methods. In the Pirkanmaa district of South Finland, all 21- to 63-year-old adults with new cases of asthma diagnosed during a 2.5-year period (n = 521 case patients, out of 441 000 inhabitants) and a random sample of control subjects from the source population (932 control subjects) participated in a population-based incident case–control study. Results. Risk of asthma was related to workplace ETS exposure (adjusted odds ratio [OR] = 2.16; 95% confidence interval [CI] = 1.26, 3.72) and home exposure (OR = 4.77; 95% CI = 1.29, 17.7) in the past year. Cumulative ETS exposure over a lifetime at work and at home increased the risk. Conclusions. This study indicates for the first time that both cumulative lifetime and recent ETS exposures increase the risk of adult-onset asthma. PMID:14652334

  10. Long-term survival after traumatic brain injury: a population-based analysis controlled for nonhead trauma.

    PubMed

    Brown, Allen W; Leibson, Cynthia L; Mandrekar, Jay; Ransom, Jeanine E; Malec, James F

    2014-01-01

    To examine the contribution of co-occurring nonhead injuries to hazard of death after traumatic brain injury (TBI). A random sample of Olmsted County, Minnesota, residents with confirmed TBI from 1987 through 1999 was identified. Each case was assigned an age- and sex-matched, non-TBI "regular control" from the population. For "special cases" with accompanying nonhead injuries, 2 matched "special controls" with nonhead injuries of similar severity were assigned. Vital status was followed from baseline (ie, injury date for cases, comparable dates for controls) through 2008. Cases were compared first with regular controls and second with regular or special controls, depending on case type. In total, 1257 cases were identified (including 221 special cases). For both cases versus regular controls and cases versus regular or special controls, the hazard ratio was increased from baseline to 6 months (10.82 [2.86-40.89] and 7.13 [3.10-16.39], respectively) and from baseline through study end (2.92 [1.74-4.91] and 1.48 [1.09-2.02], respectively). Among 6-month survivors, the hazard ratio was increased for cases versus regular controls (1.43 [1.06-2.15]) but not for cases versus regular or special controls (1.05 [0.80-1.38]). Among 6-month survivors, accounting for nonhead injuries resulted in a nonsignificant effect of TBI on long-term mortality.

  11. Level of neurotoxic metals in amyotrophic lateral sclerosis: A population-based case-control study.

    PubMed

    Bocca, Beatrice; Forte, Giovanni; Oggiano, Riccardo; Clemente, Simonetta; Asara, Yolande; Peruzzu, Angela; Farace, Cristiano; Pala, Salvatore; Fois, Alessandro Giuseppe; Pirina, Pietro; Madeddu, Roberto

    2015-12-15

    The association between exposure to toxic metals and amyotrophic lateral sclerosis (ALS) was explored in a population-based case-control study in the Sardinia island (Italy), a region characterized by elevated rates of ALS cases. In 34 patients with ALS (mean age, 62 ± 10 years) and 30 controls (mean age, 65 ± 11 years), Al, Cd, Hg, Mn and Pb were determined in blood, hair and urine by sector field inductively coupled mass spectrometry. Results indicated that, in blood, concentrations of Al (p=0.045) and Pb were higher (p=0.026) in ALS patients than in control subjects. In hair, a depletion of Al (p=0.006) and Mn (p=0.032) concentrations in ALS subjects respect to controls was found. In urine, no significant differences between cases and controls were observed. Thus, some metals seemed to be associated with ALS degeneration, but a definitive conclusion is still far considering the multiple risk factors (genetic mutations, environmental toxicants and stressors) involved in the disease. Finally, the interpretation that deregulated metal concentrations can be a consequence of the degenerative process, rather than a cause, is also valid. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Association of Drug and Alcohol Use With Adolescent Firearm Homicide at Individual, Family, and Neighborhood Levels.

    PubMed

    Hohl, Bernadette C; Wiley, Shari; Wiebe, Douglas J; Culyba, Alison J; Drake, Rebecca; Branas, Charles C

    2017-03-01

    Homicide is the third leading cause of death for adolescents in the United States and the leading cause of death for adolescents who are African American. Large cities have disproportionate homicide rates. To determine the relationships between exposures to drugs and alcohol at the individual, family, and neighborhood levels and adolescent firearm homicide and to inform new approaches to preventing firearm violence. Population-based case-control study from January 2010 to December 2012 of all 13- to 20-year-olds who were homicide victims in Philadelphia during the study period matched to randomly selected 13- to 20-year-old controls from the general population. Individual drug and alcohol use at the time of injury, history of drug and alcohol use, caregiver drug and alcohol use, and neighborhood availability of alcohol and illegal drugs. We also controlled for age, race, school suspensions, arrests, and neighborhood ethnicity. Adolescent firearm homicide identified from police and medical examiner's reports. We enrolled 161 adolescent homicide cases, including 157 (97.5%) firearm homicide cases and 172 matched controls, including 166 (96.5%) firearm homicide controls. Adolescents with a history of alcohol use (adjusted odds ratio [AOR], 4.1; 95% CI, 1.2-14.0) or drug use (AOR, 4.4; 95% CI, 1.7-11.6) had increased odds of firearm homicide. Adolescents whose caregiver had a history of drug use had increased odds of firearm homicide (AOR, 11.7; 95% CI, 2.8-48.0). Adolescents in neighborhoods with high densities of alcohol outlets (AOR, 3.2; 95% CI, 1.1-9.1) and moderate or high drug availability had increased odds of firearm homicide (AOR, 3.4; 95% CI, 1.1-10.3 vs AOR, 7.5; 95% CI, 2.2-25.8). Almost all adolescent homicides in Philadelphia between 2010 and 2012 were committed with a firearm. Substance use at the individual, family, and neighborhood levels was associated with increased odds of adolescent firearm homicide; drug use was associated at all 3 levels and alcohol at the individual and neighborhood levels. Expanding violence prevention efforts to target drug and alcohol use at multiple levels may help to reduce the firearm violence that disproportionately affects adolescents in minority populations in large US cities.

  13. Familial aggregation of childhood and adult cancer in the Utah genealogy.

    PubMed

    Neale, Rachel E; Stiller, Charles A; Bunch, Kathryn J; Milne, Elizabeth; Mineau, Geraldine P; Murphy, Michael F G

    2013-12-15

    A small proportion of childhood cancer is attributable to known hereditary syndromes, but whether there is any familial component to the remainder remains uncertain. We explored familial aggregation of cancer in a population-based case-control study using genealogical record linkage and designed to overcome limitations of previous studies. Subjects were selected from the Utah Population Database. We compared risk of cancer in adult first-degree relatives of children who were diagnosed with cancer with the risk in relatives of children who had not had a cancer diagnosed. We identified 1,894 childhood cancer cases and 3,788 controls; 7,467 relatives of cases and 14,498 relatives of controls were included in the analysis. Relatives of children with cancer had a higher risk of cancer in adulthood than relatives of children without cancer [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.11-1.56]; this was restricted to mothers and siblings and was not evident in fathers. Familial aggregation appeared stronger among relatives of cases diagnosed before 5 years of age (OR 1.48, 95% CI 1.13-1.95) than among relatives of cases who were older when diagnosed (OR 1.22, 95% CI 0.98-1.51). These findings provide evidence of a generalized excess of cancer in the mothers and siblings of children with cancer. The tendency for risk to be higher in the relatives of children who were younger at cancer diagnosis should be investigated in other large data sets. The excesses of thyroid cancer in parents of children with cancer and of any cancer in relatives of children with leukemia merit further investigation. Copyright © 2013 UICC.

  14. Long-term Mortality Risk After Hyperglycemic Crisis Episodes in Geriatric Patients With Diabetes: A National Population-Based Cohort Study.

    PubMed

    Huang, Chien-Cheng; Weng, Shih-Feng; Tsai, Kang-Ting; Chen, Ping-Jen; Lin, Hung-Jung; Wang, Jhi-Joung; Su, Shih-Bin; Chou, Willy; Guo, How-Ran; Hsu, Chien-Chin

    2015-05-01

    Hyperglycemic crisis is one of the most serious diabetes-related complications. The increase in the prevalence of diabetes in the geriatric population leads to a large disease burden, but previous studies of geriatric hyperglycemic crisis were focused on acute hyperglycemic crisis episode (HCE). This study aimed to delineate the long-term mortality risk after HCE. This retrospective national population-based cohort study reviewed, in Taiwan's National Health Insurance Research Database, data from 13,551 geriatric patients with new-onset diabetes between 2000 and 2002, including 4,517 with HCE (case subjects) (ICD-9 code 250.1 or 250.2) and 9,034 without HCE (control subjects). The groups were compared and followed until 2011. One thousand six hundred thirty-four (36.17%) case and 1,692 (18.73%) control subjects died (P < 0.0001) during follow-up. Incidence rate ratios (IRRs) of death were 2.82 times higher in case subjects (P < 0.0001). The mortality risk was highest in the first month (IRR 26.56; 95% CI 17.97-39.27) and remained higher until 4-6 years after the HCE (IRR 1.49; 95% CI 1.23-1.81). After adjustment for age, sex, selected comorbidities, and monthly income, the mortality hazard ratio was still 2.848 and 4.525 times higher in case subjects with one episode and two or more episodes of hyperglycemic crisis, respectively. Older age, male sex, renal disease, stroke, cancer, chronic obstructive pulmonary disease, and congestive heart failure were independent mortality predictors. Patients with diabetes had a higher mortality risk after HCE during the first 6 years of follow-up. Referral for proper education, better access to medical care, effective communication with a health care provider, and control of comorbidities should be done immediately after HCE. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  15. Association of CLU and PICALM variants with Alzheimer's disease

    PubMed Central

    Kamboh, M.I.; Minster, R. L.; Demirci, F.Y.; Ganguli, M.; DeKosky, S.T.; Lopez, O.L.; Barmada, M.M.

    2010-01-01

    Two recent large genome-wide association studies have reported significant associations in the CLU (APOJ), CR1 and PICALM genes. In order to replicate these findings, we examined 7 single nucleotide polymorphisms (SNPs) most significantly implicated by these studies in a large case-control sample comprising of 2,707 individuals. Principle components analysis revealed no population substructure in our sample. While no association was observed with CR1 SNPs (P=0.30–0.457), a trend of association was seen with the PICALM (P=0.071–0.086) and CLU (P=0.148–0.258) SNPs. A meta-analysis of three studies revealed significant associations with all three genes. Our data from an independent and large case-control sample suggest that these gene regions should be followed up by comprehensive resequencing to find functional variants. PMID:20570404

  16. Neovascular age-related macular degeneration is not associated with coronary heart disease in a Chinese Population: a population-based study.

    PubMed

    Hu, Chao-Chien; Lin, Herng-Ching; Sheu, Jau-Jiuan; Kao, Li-Ting

    2017-11-01

    This case-control study aimed to explore the association between prior coronary heart disease (CHD) and neovascular age-related macular degeneration (AMD) using a population-based data set in Taiwan. We analysed data sourced from the Taiwan Longitudinal Health Insurance Database 2005. The study consisted of 1970 patients with neovascular AMD as cases and 5910 age- and sex-matched controls. We performed a conditional logistic regression to examine the odds ratio (OR) and its corresponding 95% confidence interval (CI) for previously diagnosed CHD between cases and controls. Of the 7880 sampled patients, 24.5% had a prior history of CHD; CHD was found in 25.7% of cases and in 22.7% of controls (p = 0.008). The conditional logistic regression analysis indicated that the OR for prior CHD for cases was 1.17 [95% confidence interval (CI): 1.04-1.32] compared to the controls. However, after adjusting for patient's monthly income, geographic location, urbanization level, age, hyperlipidaemia, diabetes and hypertension, we failed to observe an association between prior CHD and AMD (OR = 1.03, 95% CI = 0.91-1.17). Additionally, the medical comorbidities of hyperlipidaemia (adjusted OR = 1.29, 95% CI = 1.15-1.45), hypertension (adjusted OR = 1.20, 95% CI = 1.05-1.37) and diabetes (adjusted OR = 1.47, 95% CI = 1.32-1.65) were significantly associated with AMD. This study presented no significant difference in the odds of prior CHD between patients with AMD and those without AMD after adjusting for comorbidities and sociodemographic characteristics in a Chinese population. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  17. A case-control study: occupational cooking and the risk of uveal melanoma

    PubMed Central

    2010-01-01

    Background A European-wide population based case-control study (European rare cancer study) undertaken in nine European countries examined risk factors for uveal melanoma. They found a positive association between cooks and the risk of uveal melanoma. In our study we examine whether cooks or people who worked in cook related jobs have an increased uveal melanoma risk. Methods We conducted a case-control study during 2002 and 2005. Overall, 1653 eligible subjects (age range: 20-74 years, living in Germany) participated. Interviews were conducted with 459 incident uveal melanoma cases, 827 population controls, 180 ophthalmologist controls and 187 sibling controls. Data on occupational exposure were obtained from a self-administered postal questionnaire and a computer-assisted telephone interview. We used conditional logistic regression to estimate odds ratios adjusting for the matching factors. Results Overall, we did not observe an increased risk of uveal melanoma among people who worked as cooks or who worked in cook related jobs. When we restricted the source population of our study to the population of the Federal State of Northrhine-Westphalia, we observed an increased risk among subjects who were categorized as cooks in the cases-control analysis. Conclusion Our results are in conflict with former results of the European rare cancer study. Considering the rarity of the disease laboratory in vitro studies of human uveal melanoma cell lines should be done to analyze potential exposure risk factors like radiation from microwaves, strong light from incandescent ovens, or infrared radiation. PMID:20969762

  18. Attitudes and Perception Towards Eye Donation in Patients with Corneal Disease: A Case-controlled Population-based Study.

    PubMed

    Noopur, Gupta; Praveen, Vashist; Radhika, Tandon; Sanjeev K, Gupta; Mani, Kalaivani; Deepak, Kumar

    2018-06-01

    To assess awareness, barriers, and misconceptions related to eye donation in people with corneal disease as compared to controls in a population setting. A population-based study was conducted in 25 randomly selected clusters of Rural Gurgaon, Haryana, India, as part of the CORE (Cornea Opacity Rural Epidemiological) study. In addition to ophthalmic examination, knowledge and perceptions regarding eye donation were assessed through a validated questionnaire. The questionnaire captured the sociodemographic factors influencing awareness regarding eye donation in participants with corneal disease and twice the number of age- and gender-matched controls recruited from the same study clusters. Descriptive statistics were computed along with multivariable logistic regression analysis to determine associated factors for awareness of eye donation. In the CORE study, 452 participants had corneal opacities on ocular examination. Of these, 442 were assessed for eye donation awareness. Additionally, 884 age- and gender-matched controls were recruited. The mean age of cases and controls was 60.9 ± 15.5 and 59.6 ± 14.3 years, respectively. Awareness of eye donation in cases and controls was 46.4% (n = 205 of 442) and 52.3% (n = 462 of 884), respectively (P = 0.044). Educational status was an important factor determining knowledge about eye donation in both cases and controls (P = < 0.001). Major barriers reported for not pledging eyes were lack of willingness (36.7%) and ignorance (15.3%). Common misconceptions like eyes could be donated before death or even after 24 h of death and that any type of blindness could be treated with corneal transplantation were prevalent. The study demonstrated that although there is substantial awareness about eye donation, there are numerous barriers in this population that need to be resolved to improve donation rates. Additional efforts are needed to translate this awareness into actual eye donation in both cases with corneal disease and controls.

  19. Exposure to ambient air pollution and the incidence of dementia: A population-based cohort study.

    PubMed

    Chen, Hong; Kwong, Jeffrey C; Copes, Ray; Hystad, Perry; van Donkelaar, Aaron; Tu, Karen; Brook, Jeffrey R; Goldberg, Mark S; Martin, Randall V; Murray, Brian J; Wilton, Andrew S; Kopp, Alexander; Burnett, Richard T

    2017-11-01

    Emerging studies have implicated air pollution in the neurodegenerative processes. Less is known about the influence of air pollution, especially at the relatively low levels, on developing dementia. We conducted a population-based cohort study in Ontario, Canada, where the concentrations of pollutants are among the lowest in the world, to assess whether air pollution exposure is associated with incident dementia. The study population comprised all Ontario residents who, on 1 April 2001, were 55-85years old, Canadian-born, and free of physician-diagnosed dementia (~2.1 million individuals). Follow-up extended until 2013. We used population-based health administrative databases with a validated algorithm to ascertain incident diagnosis of dementia as well as prevalent cases. Using satellite observations, land-use regression model, and an optimal interpolation method, we derived long-term average exposure to fine particulate matter (≤2.5μm in diameter) (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ), respectively at the subjects' historical residences based on a population-based registry. We used multilevel spatial random-effects Cox proportional hazards models, adjusting for individual and contextual factors, such as diabetes, brain injury, and neighborhood income. We conducted various sensitivity analyses, such as lagging exposure up to 10years and considering a negative control outcome for which no (or weaker) association with air pollution is expected. We identified 257,816 incident cases of dementia in 2001-2013. We found a positive association between PM 2.5 and dementia incidence, with a hazard ratio (HR) of 1.04 (95% confidence interval (CI): 1.03-1.05) for every interquartile-range increase in exposure to PM 2.5 . Similarly, NO 2 was associated with increased incidence of dementia (HR=1.10; 95% CI: 1.08-1.12). No association was found for O 3 . These associations were robust to all sensitivity analyses examined. These estimates translate to 6.1% of dementia cases (or 15,813 cases) attributable to PM 2.5 and NO 2 , based on the observed distribution of exposure relative to the lowest quartile in concentrations in this cohort. In this large cohort, exposure to air pollution, even at the relative low levels, was associated with higher dementia incidence. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  20. Differences in child versus parent reports of the child's health-related quality of life in children with epilepsy and healthy siblings.

    PubMed

    Baca, Christine Bower; Vickrey, Barbara G; Hays, Ron D; Vassar, Stefanie D; Berg, Anne T

    2010-01-01

    Self versus proxy perspectives may produce different results that are important for clinical decision-making and for assessing outcomes in research studies. We examined differences in child versus parent report of the child's health-related quality of life (HRQOL) in a large prospective, community-based study of newly diagnosed childhood epilepsy that included children with epilepsy (case) and sibling controls. HRQOL was assessed 8 to 9 years after initial diagnosis of epilepsy in a subset of 143 case-control matched pairs using the Child Health Questionnaire (CHQ), a generic HRQOL measure with child (CHQ-CF87), and parent (CHQ-PF50) versions. There were no significant differences between self-reported case and sibling control HRQOL scores on 9 of 11 scales or 2 global items. Nevertheless, parent ratings were significantly better (higher HRQOL) for sibling controls compared with epilepsy cases on 10 of 12 scales, global behavior and general health items, and the physical and psychosocial summary scores (P≤0.05). Parent-child agreement was low for cases and controls (kappa 0.27-0.33) for three single-item questions with the same wording on parent and child versions. Parent ratings of the case's HRQOL were often significantly associated with 5-year remission status and current antiepileptic drug use, but the case's self-reported HRQOL scores were not. In contrast, current pharmacoresistance was often associated with the child and parent ratings of the child's HRQOL. Children with epilepsy report HRQOL that is comparable to that of sibling controls, while parents rate children with epilepsy as having lower HRQOL than sibling controls. Measuring outcomes in studies of this population should incorporate both perspectives. © 2010, International Society for Pharmacoeconomics and Outcomes Research (ISPOR).

  1. Hepatitis C virus infection and the risk of cancer among elderly US adults: A registry-based case-control study.

    PubMed

    Mahale, Parag; Torres, Harrys A; Kramer, Jennifer R; Hwang, Lu-Yu; Li, Ruosha; Brown, Eric L; Engels, Eric A

    2017-04-01

    Hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC) and subtypes of non-Hodgkin lymphoma (NHL). Associations with other cancers are not established. The authors systematically assessed associations between HCV infection and cancers in the US elderly population. This was a registry-based case-control study using Surveillance, Epidemiology, and End Results (SEER)-Medicare data in US adults aged ≥66 years. Cases (n = 1,623,538) were patients who had first cancers identified in SEER registries (1993-2011). Controls (n = 200,000) were randomly selected, cancer-free individuals who were frequency-matched to cases on age, sex, race, and calendar year. Associations with HCV (documented by Medicare claims) were determined using logistic regression. HCV prevalence was higher in cases than in controls (0.7% vs 0.5%). HCV was positively associated with cancers of the liver (adjusted odds ratio [aOR] = 31.5; 95% confidence interval [CI], 29.0-34.3), intrahepatic bile duct (aOR, 3.40; 95% CI, 2.52-4.58), extrahepatic bile duct (aOR, 1.90; 95% CI, 1.41-2.57), pancreas (aOR, 1.23; 95% CI, 1.09-1.40), and anus (aOR, 1.97; 95% CI, 1.42-2.73); nonmelanoma nonepithelial skin cancer (aOR, 1.53; 95% CI, 1.15-2.04); myelodysplastic syndrome (aOR, 1.56; 95% CI, 1.33-1.83); and diffuse large B-cell lymphoma (aOR, 1.57; 95% CI, 1.34-1.84). Specific skin cancers associated with HCV were Merkel cell carcinoma (aOR, 1.92; 95% CI, 1.30-2.85) and appendageal skin cancers (aOR, 2.02; 95% CI, 1.29-3.16). Inverse associations were observed with uterine cancer (aOR, 0.64; 95% CI, 0.51-0.80) and prostate cancer (aOR, 0.73; 95% CI, 0.66-0.82). Associations were maintained in sensitivity analyses conducted among individuals without documented alcohol abuse, cirrhosis, or hepatitis B or human immunodeficiency virus infections and after adjustment for socioeconomic status. Associations of HCV with other cancers were not observed. HCV is associated with increased risk of cancers other than HCC in the US elderly population, notably bile duct cancers and diffuse large B-cell lymphoma. These results support a possible etiologic role for HCV in an expanded group of cancers. Cancer 2017;123:1202-1211. © 2016 American Cancer Society. © 2017 American Cancer Society.

  2. Indoor pollution as an occupational risk factor for tuberculosis among women: a population-based, gender oriented, case-control study in Southern Mexico.

    PubMed

    García-Sancho, Ma Cecilia; García-García, Lourdes; Báez-Saldaña, Renata; Ponce-De-León, Alfredo; Sifuentes-Osornio, José; Bobadilla-Del-valle, Miriam; Ferreyra-Reyes, Leticia; Cano-Arellano, Bulmaro; Canizales-Quintero, Sergio; Palacios-Merino, Luz del Carmen; Juárez-Sandino, Luis; Ferreira-Guerrero, Elizabeth; Cruz-Hervert, Luis Pablo; Small, Peter M; Pérez-Padilla, José Rogelio

    2009-01-01

    Indoor air pollution produced by biomass cooking fuels in developing countries has been associated with acute and chronic lower respiratory diseases, but has not been identified as an occupational exposure among women. To examine the relationship between the use of biomass cooking fuels (mainly wood) and tuberculosis (TB) among women living in rural areas in Southern Mexico. We conducted a population based case-control study in the health jurisdiction of Orizaba, Mexico. Cases were all incident female pulmonary TB patients, with Mycobacterium tuberculosis in sputum, living in communities with fewer than 15,000 inhabitants, diagnosed between March 1995 and April 2003. Woodsmoke exposure was assessed by applying a standardized questionnaire (ATS-DLD-78 questionnaire). Controls were randomly selected from sex-matched neighbors. Appropriate IRB approval was obtained. 42 TB cases and 84 community controls were recruited. Multivariate assessment showed that more than 20 years of exposure to smoke from biomass fuels was three times more frequent among cases than among controls [Odds ratio (OR): 3.3, 95% confidence interval (CI):1.06-10.30, p = 0.03], after controlling for age, body mass, household crowding, years of formal education and tobacco use. We found a strong association between the use of biomass cooking fuels and tuberculosis among women in a community-based, case-control study. Results of this study are intended to provide evidence to policy makers, community leaders and the general public on the importance of implementing gender oriented interventions that decrease the use of biomass fuels in poor communities in developing countries.

  3. Risk factors of tuberculosis among health care workers in Sabah, Malaysia.

    PubMed

    Jelip, Jenarun; Mathew, George G; Yusin, Tanrang; Dony, Jiloris F; Singh, Nirmal; Ashaari, Musa; Lajanin, Noitie; Shanmuga Ratnam, C; Yusof Ibrahim, Mohd; Gopinath, Deyer

    2004-01-01

    Tuberculosis (TB) is one of the main public health problems in Sabah; 30% of the total number of TB cases reported in Malaysia every year occur in Sabah. The average incidence of TB among health care workers over the past 5 years is 280.4 per 100,000 population (1, Annual Report of Sabah State TB Control Programme, 1998). At present, there are no specific measures for the prevention of TB transmission in health care facilities. A case-control study was conducted among health care workers in Sabah in 2000-2001. Cases were health care workers with TB diagnosed between January 1990 and June 2000. Controls were health care workers without TB and working in the same facility as cases during the disease episode. The study attempted to identify risk factors for TB among the study population. Data were collected through structured interviews and review of patients' records. The notification rate of TB among health care workers was significantly higher than that to the general population (Z=4.893, p<0.01). The average notification rate of TB among health care workers over the last 5 years was two times higher than in the general population (280.4/100,000 compared to 153.9/100,000). Regression results showed that ethnicity, designation, family contact and TB related knowledge did not significantly contribute to the risk of contracting TB in this study. However, after controlling for the above factors, age, gender, history of TB contact outside the workplace (other than family contact), duration of service and failure to use respiratory protection when performing high-risk procedures, were the main risk factors of TB among health care workers. This study succeeded in identifying some of the risk factors of TB among health care workers. We managed to include the large ratio of controls to case (3:1) and those cases spanned over a period of 10 years. However, the findings from the study have to be applied with caution due to the limitations of this study, which include recall bias, dropouts, and small sample size. Based on the study findings, we recommend that health care workers in the first 10 years of service should take extra precautions, such as using respiratory protection when performing procedures that are considered to be of high risk with respect to TB infection. They should also undergo TB screening at least once every 2 years and, if symptomatic, offered prophylactic treatment. The Respiratory Protection Programme should be fully implemented to help reduce the risk of TB among health care workers in Sabah.

  4. Patterns of population subdivision, gene flow and genetic variability in the African wild dog (Lycaon pictus).

    PubMed

    Girman, D J; Vilà, C; Geffen, E; Creel, S; Mills, M G; McNutt, J W; Ginsberg, J; Kat, P W; Mamiya, K H; Wayne, R K

    2001-07-01

    African wild dogs are large, highly mobile carnivores that are known to disperse over considerable distances and are rare throughout much of their geographical range. Consequently, genetic variation within and differentiation between geographically separated populations is predicted to be minimal. We determined the genetic diversity of mitochondrial DNA (mtDNA) control region sequences and microsatellite loci in seven populations of African wild dogs. Analysis of mtDNA nucleotide diversity suggests that, historically, wild dog populations have been small relative to other large carnivores. However, population declines due to recent habitat loss have not caused a dramatic reduction in genetic diversity. We found one historical and eight recent mtDNA genotypes in 280 individuals that defined two highly divergent clades. In contrast to a previous, more limited, mtDNA analysis, sequences from these clades are not geographically restricted to eastern or southern African populations. Rather, we found a large admixture zone spanning populations from Botswana, Zimbabwe and south-eastern Tanzania. Mitochondrial and microsatellite differentiation between populations was significant and unique mtDNA genotypes and alleles characterized the populations. However, gene flow estimates (Nm) based on microsatellite data were generally greater than one migrant per generation. In contrast, gene flow estimates based on the mtDNA control region were lower than expected given differences in the mode of inheritance of mitochondrial and nuclear markers which suggests a male bias in long-distance dispersal.

  5. Asthma and Attention-Deficit/Hyperactivity Disorder: A Nationwide Population-Based Prospective Cohort Study

    ERIC Educational Resources Information Center

    Chen, Mu-Hong; Su, Tung-Ping; Chen, Ying-Sheue; Hsu, Ju-Wei; Huang, Kai-Lin; Chang, Wen-Han; Chen, Tzeng-Ji; Bai, Ya-Mei

    2013-01-01

    Background: Previous cross-sectional studies have suggested an association between asthma and attention-deficit/hyperactivity disorder (ADHD), but the temporal relationship was not determined. Using a nationwide population-based prospective case-control cohort study (1:4, age-/gender-matched), we hypothesized that asthma in infanthood or early…

  6. Ensuring quality in studies linking cancer registries and biobanks.

    PubMed

    Langseth, Hilde; Luostarinen, Tapio; Bray, Freddie; Dillner, Joakim

    2010-04-01

    The Nordic countries have a long tradition of providing comparable and high quality cancer data through the national population-based cancer registries and the capability to link the diverse large-scale biobanks currently in operation. The joining of these two infrastructural resources can provide a study base for large-scale studies of etiology, treatment and early detection of cancer. Research projects based on combined data from cancer registries and biobanks provides great opportunities, but also presents major challenges. Biorepositories have become an important resource in molecular epidemiology, and the increased interest in performing etiological, clinical and gene-environment-interaction studies, involving information from biological samples linked to population-based cancer registries, warrants a joint evaluation of the quality aspects of the two resources, as well as an assessment of whether the resources can be successfully combined into a high quality study. While the quality of biospecimen handling and analysis is commonly considered in different studies, the logistics of data handling including the linkage of the biobank with the cancer registry is an overlooked aspect of a biobank-based study. It is thus the aim of this paper to describe recommendations on data handling, in particular the linkage of biobank material to cancer registry data and the quality aspects thereof, based on the experience of Nordic collaborative projects combining data from cancer registries and biobanks. We propose a standard documentation with respect to the following topics: the quality control aspects of cancer registration, the identification of cases and controls, the identification and use of data confounders, the stability of serum components, historical storage conditions, aliquoting history, the number of freeze/thaw cycles and available volumes.

  7. Methodology Series Module 2: Case-control Studies.

    PubMed

    Setia, Maninder Singh

    2016-01-01

    Case-Control study design is a type of observational study. In this design, participants are selected for the study based on their outcome status. Thus, some participants have the outcome of interest (referred to as cases), whereas others do not have the outcome of interest (referred to as controls). The investigator then assesses the exposure in both these groups. The investigator should define the cases as specifically as possible. Sometimes, definition of a disease may be based on multiple criteria; thus, all these points should be explicitly stated in case definition. An important aspect of selecting a control is that they should be from the same 'study base' as that of the cases. We can select controls from a variety of groups. Some of them are: General population; relatives or friends; and hospital patients. Matching is often used in case-control control studies to ensure that the cases and controls are similar in certain characteristics, and it is a useful technique to increase the efficiency of the study. Case-Control studies can usually be conducted relatively faster and are inexpensive - particularly when compared with cohort studies (prospective). It is useful to study rare outcomes and outcomes with long latent periods. This design is not very useful to study rare exposures. Furthermore, they may also be prone to certain biases - selection bias and recall bias.

  8. A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder.

    PubMed

    Martin, Joanna; Walters, Raymond K; Demontis, Ditte; Mattheisen, Manuel; Lee, S Hong; Robinson, Elise; Brikell, Isabell; Ghirardi, Laura; Larsson, Henrik; Lichtenstein, Paul; Eriksson, Nicholas; Werge, Thomas; Mortensen, Preben Bo; Pedersen, Marianne Giørtz; Mors, Ole; Nordentoft, Merete; Hougaard, David M; Bybjerg-Grauholm, Jonas; Wray, Naomi R; Franke, Barbara; Faraone, Stephen V; O'Donovan, Michael C; Thapar, Anita; Børglum, Anders D; Neale, Benjamin M

    2018-06-15

    Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls). Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with r g estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98-1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11-1.18], p = 1.5E-15). Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  9. Detailed Investigation of the Role of Common and Low-Frequency WFS1 Variants in Type 2 Diabetes Risk

    PubMed Central

    Fawcett, Katherine A.; Wheeler, Eleanor; Morris, Andrew P.; Ricketts, Sally L.; Hallmans, Göran; Rolandsson, Olov; Daly, Allan; Wasson, Jon; Permutt, Alan; Hattersley, Andrew T.; Glaser, Benjamin; Franks, Paul W.; McCarthy, Mark I.; Wareham, Nicholas J.; Sandhu, Manjinder S.; Barroso, Inês

    2010-01-01

    OBJECTIVE Wolfram syndrome 1 (WFS1) single nucleotide polymorphisms (SNPs) are associated with risk of type 2 diabetes. In this study we aimed to refine this association and investigate the role of low-frequency WFS1 variants in type 2 diabetes risk. RESEARCH DESIGN AND METHODS For fine-mapping, we sequenced WFS1 exons, splice junctions, and conserved noncoding sequences in samples from 24 type 2 diabetic case and 68 control subjects, selected tagging SNPs, and genotyped these in 959 U.K. type 2 diabetic case and 1,386 control subjects. The same genomic regions were sequenced in samples from 1,235 type 2 diabetic case and 1,668 control subjects to compare the frequency of rarer variants between case and control subjects. RESULTS Of 31 tagging SNPs, the strongest associated was the previously untested 3′ untranslated region rs1046320 (P = 0.008); odds ratio 0.84 and P = 6.59 × 10−7 on further replication in 3,753 case and 4,198 control subjects. High correlation between rs1046320 and the original strongest SNP (rs10010131) (r2 = 0.92) meant that we could not differentiate between their effects in our samples. There was no difference in the cumulative frequency of 82 rare (minor allele frequency [MAF] <0.01) nonsynonymous variants between type 2 diabetic case and control subjects (P = 0.79). Two intermediate frequency (MAF 0.01–0.05) nonsynonymous changes also showed no statistical association with type 2 diabetes. CONCLUSIONS We identified six highly correlated SNPs that show strong and comparable associations with risk of type 2 diabetes, but further refinement of these associations will require large sample sizes (>100,000) or studies in ethnically diverse populations. Low frequency variants in WFS1 are unlikely to have a large impact on type 2 diabetes risk in white U.K. populations, highlighting the complexities of undertaking association studies with low-frequency variants identified by resequencing. PMID:20028947

  10. Physical activity and survival among Hispanic and non-Hispanic white long-term breast cancer survivors and population-based controls.

    PubMed

    Pinkston, Christina M; Baumgartner, Richard N; Connor, Avonne E; Boone, Stephanie D; Baumgartner, Kathy B

    2015-12-01

    We investigated the association of physical activity with survival for 601 Hispanic women and 682 non-Hispanic white women who participated in the population-based breast cancer case-control New Mexico Women's Health Study. We identified 240 deaths among cases diagnosed with a first primary invasive breast cancer between 1992 and 1994, and 88 deaths among controls. Follow-up extended through 2012 for cases and 2008 for controls. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Higher levels of total physical activity were inversely associated with all-cause mortality among Hispanic cases (Quartile (Q)4: HR = 0.55, 95% CI 0.31-0.99). A non-significant trend was observed for recreational activity in Hispanic cases also (Q4: HR = 0.50, 95% CI 0.23-1.09, p for trend = 0.08). No significant associations were noted for non-Hispanic white cases or for controls. The results suggest that increasing physical activity may be protective against mortality in Hispanic women with breast cancer, despite reporting lower levels of recreational activity than non-Hispanic white women or Hispanic controls. Public health programs in Hispanic communities should promote physical activity in women as a means of decreasing breast cancer risk and improving survival.

  11. Identification and medical utilization of incident cases of alcohol dependence: A population-based case-control study.

    PubMed

    Pan, Chun-Hung; Li, Min-Shan; Yang, Tien-Wey; Huang, Ming-Chyi; Su, Sheng-Shiang; Hung, Yen-Ni; Chen, Chiao-Chicy; Kuo, Chian-Jue

    2018-05-05

    Patients with alcohol dependence (AD) often seek help from medical professionals due to alcohol-related diseases, but the overall distribution of medical specialties identifying new AD cases is unclear. We investigated how such cases were identified and how medical resources were utilized before the identification of AD in a nationwide cohort. We enrolled a population-based cohort (N = 1,000,000) using the National Health Insurance Research Database of Taiwan; 8181 cases with incident AD were retrieved between January 1, 2000, and December 31, 2010. For this nested case-control study, four controls were matched for age and sex with each case based on risk-set sampling. We measured various dimensions of medical utilization before AD was diagnosed, including department visited, physical comorbidity, and medication used. Conditional logistic regression was used for estimating the variables associated with AD. Patients living in less urbanized areas who were unemployed were more likely to develop AD. The highest proportions (34.2%) of AD cases were identified in the internal medicine department, followed by the emergency (22.3%) and psychiatry (18.7%) departments. AD patients had a higher risk of comorbid chronic hepatic disease (adjusted RR = 2.72, p < 0.001) before identification of AD than controls. AD patients also had greater numbers of hospital admissions than controls, including non-psychiatric and psychiatric hospitalizations. Outpatient visit numbers were similar for AD patients and controls. The findings indicate that clinicians providing care in diverse medical settings should be prepared to screen for unhealthy alcohol use and to mitigate its detrimental effects. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Estimation of the probability of exposure to metalworking fluids in a population-based case-control study

    PubMed Central

    Park, Dong-Uk; Colt, Joanne S.; Baris, Dalsu; Schwenn, Molly; Karagas, Margaret R.; Armenti, Karla R.; Johnson, Alison; Silverman, Debra T; Stewart, Patricia A

    2014-01-01

    We describe here an approach for estimating the probability that study subjects were exposed to metalworking fluids (MWFs) in a population-based case-control study of bladder cancer. Study subject reports on the frequency of machining and use of specific MWFs (straight, soluble, and synthetic/semi-synthetic) were used to estimate exposure probability when available. Those reports also were used to develop estimates for job groups, which were then applied to jobs without MWF reports. Estimates using both cases and controls and controls only were developed. The prevalence of machining varied substantially across job groups (10-90%), with the greatest percentage of jobs that machined being reported by machinists and tool and die workers. Reports of straight and soluble MWF use were fairly consistent across job groups (generally, 50-70%). Synthetic MWF use was lower (13-45%). There was little difference in reports by cases and controls vs. controls only. Approximately, 1% of the entire study population was assessed as definitely exposed to straight or soluble fluids in contrast to 0.2% definitely exposed to synthetic/semi-synthetics. A comparison between the reported use of the MWFs and the US production levels by decade found high correlations (r generally >0.7). Overall, the method described here is likely to have provided a systematic and reliable ranking that better reflects the variability of exposure to three types of MWFs than approaches applied in the past. PMID:25256317

  13. Risk factors for first trimester miscarriage--results from a UK-population-based case-control study.

    PubMed

    Maconochie, N; Doyle, P; Prior, S; Simmons, R

    2007-02-01

    The aim of this study was to examine the association between biological, behavioural and lifestyle risk factors and risk of miscarriage. Population-based case-control study. Case-control study nested within a population-based, two-stage postal survey of reproductive histories of women randomly sampled from the UK electoral register. Six hundred and three women aged 18-55 years whose most recent pregnancy had ended in first trimester miscarriage (<13 weeks of gestation; cases) and 6116 women aged 18-55 years whose most recent pregnancy had progressed beyond 12 weeks (controls). Women were questioned about socio-demographic, behavioural and other factors in their most recent pregnancy. First trimester miscarriage. After adjustment for confounding, the following were independently associated with increased risk: high maternal age; previous miscarriage, termination and infertility; assisted conception; low pre-pregnancy body mass index; regular or high alcohol consumption; feeling stressed (including trend with number of stressful or traumatic events); high paternal age and changing partner. Previous live birth, nausea, vitamin supplementation and eating fresh fruits and vegetables daily were associated with reduced risk, as were feeling well enough to fly or to have sex. After adjustment for nausea, we did not confirm an association with caffeine consumption, smoking or moderate or occasional alcohol consumption; nor did we find an association with educational level, socio-economic circumstances or working during pregnancy. The results confirm that advice to encourage a healthy diet, reduce stress and promote emotional wellbeing might help women in early pregnancy (or planning a pregnancy) reduce their risk of miscarriage. Findings of increased risk associated with previous termination, stress, change of partner and low pre-pregnancy weight are noteworthy, and we recommend further work to confirm these findings in other study populations.

  14. Prescriptions for selective cyclooxygenase-2 inhibitors, non-selective non-steroidal anti-inflammatory drugs, and risk of breast cancer in a population-based case-control study.

    PubMed

    Cronin-Fenton, Deirdre P; Pedersen, Lars; Lash, Timothy L; Friis, Søren; Baron, John A; Sørensen, Henrik T

    2010-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) prevent the growth of mammary tumours in animal models. Two population-based case-control studies suggest a reduced risk of breast cancer associated with selective cyclooxygenase-2 (sCox-2) inhibitor use, but data regarding the association between breast cancer occurrence and use of non-selective NSAIDs are conflicting. We conducted a population-based case-control study using Danish healthcare databases to examine if use of NSAIDs, including sCox-2 inhibitors, was associated with a reduced risk of breast cancer. We included 8,195 incident breast cancer cases diagnosed in 1991 through 2006 and 81,950 population controls. Overall, we found no reduced breast cancer risk in ever users (>2 prescriptions) of sCox-2 inhibitors (odds ratio (OR) = 1.08, 95% confidence interval (95% CI) = 0.99, 1.18), aspirin (OR = 0.98, 95% CI = 0.90-1.07), or non-selective NSAIDs OR = 1.04, (95% CI = 0.98, 1.10)). Recent use (>2 prescriptions within two years of index date) of sCox-2 inhibitors, aspirin, or non-selective NSAIDs was likewise not associated with breast cancer risk (Ors = 1.06 (95% CI = 0.96, 1.18), 0.96 (95% CI = 0.87, 1.06) and 0.99 (95% CI = 0.85, 1.16), respectively). Risk estimates by duration (<10, 10 to 15, 15+ years) or intensity (low/medium/high) of NSAID use were also close to unity. Regardless of intensity, shorter or long-term NSAID use was not significantly associated with breast cancer risk. Overall, we found no compelling evidence of a reduced risk of breast cancer associated with use of sCox-2 inhibitors, aspirin, or non-selective NSAIDs.

  15. CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.

    PubMed

    Nag, Abhishek; Bochukova, Elena G; Kremeyer, Barbara; Campbell, Desmond D; Muller, Heike; Valencia-Duarte, Ana V; Cardona, Julio; Rivas, Isabel C; Mesa, Sandra C; Cuartas, Mauricio; Garcia, Jharley; Bedoya, Gabriel; Cornejo, William; Herrera, Luis D; Romero, Roxana; Fournier, Eduardo; Reus, Victor I; Lowe, Thomas L; Farooqi, I Sadaf; Mathews, Carol A; McGrath, Lauren M; Yu, Dongmei; Cook, Ed; Wang, Kai; Scharf, Jeremiah M; Pauls, David L; Freimer, Nelson B; Plagnol, Vincent; Ruiz-Linares, Andrés

    2013-01-01

    Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400 kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.

  16. CNV Analysis in Tourette Syndrome Implicates Large Genomic Rearrangements in COL8A1 and NRXN1

    PubMed Central

    Nag, Abhishek; Bochukova, Elena G.; Kremeyer, Barbara; Campbell, Desmond D.; Muller, Heike; Valencia-Duarte, Ana V.; Cardona, Julio; Rivas, Isabel C.; Mesa, Sandra C.; Cuartas, Mauricio; Garcia, Jharley; Bedoya, Gabriel; Cornejo, William; Herrera, Luis D.; Romero, Roxana; Fournier, Eduardo; Reus, Victor I.; Lowe, Thomas L.; Farooqi, I. Sadaf; Mathews, Carol A.; McGrath, Lauren M.; Yu, Dongmei; Cook, Ed; Wang, Kai; Scharf, Jeremiah M.; Pauls, David L.; Freimer, Nelson B.; Plagnol, Vincent; Ruiz-Linares, Andrés

    2013-01-01

    Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions. PMID:23533600

  17. Rapid case-based mapping of seasonal malaria transmission risk for strategic elimination planning in Swaziland

    PubMed Central

    2013-01-01

    Background As successful malaria control programmes move towards elimination, they must identify residual transmission foci, target vector control to high-risk areas, focus on both asymptomatic and symptomatic infections, and manage importation risk. High spatial and temporal resolution maps of malaria risk can support all of these activities, but commonly available malaria maps are based on parasite rate, a poor metric for measuring malaria at extremely low prevalence. New approaches are required to provide case-based risk maps to countries seeking to identify remaining hotspots of transmission while managing the risk of transmission from imported cases. Methods Household locations and travel histories of confirmed malaria patients during 2011 were recorded through routine surveillance by the Swaziland National Malaria Control Programme for the higher transmission months of January to April and the lower transmission months of May to December. Household locations for patients with no travel history to endemic areas were compared against a random set of background points sampled proportionate to population density with respect to a set of variables related to environment, population density, vector control, and distance to the locations of identified imported cases. Comparisons were made separately for the high and low transmission seasons. The Random Forests regression tree classification approach was used to generate maps predicting the probability of a locally acquired case at 100 m resolution across Swaziland for each season. Results Results indicated that case households during the high transmission season tended to be located in areas of lower elevation, closer to bodies of water, in more sparsely populated areas, with lower rainfall and warmer temperatures, and closer to imported cases than random background points (all p < 0.001). Similar differences were evident during the low transmission season. Maps from the fit models suggested better predictive ability during the high season. Both models proved useful at predicting the locations of local cases identified in 2012. Conclusions The high-resolution mapping approaches described here can help elimination programmes understand the epidemiology of a disappearing disease. Generating case-based risk maps at high spatial and temporal resolution will allow control programmes to direct interventions proactively according to evidence-based measures of risk and ensure that the impact of limited resources is maximized to achieve and maintain malaria elimination. PMID:23398628

  18. Rapid case-based mapping of seasonal malaria transmission risk for strategic elimination planning in Swaziland.

    PubMed

    Cohen, Justin M; Dlamini, Sabelo; Novotny, Joseph M; Kandula, Deepika; Kunene, Simon; Tatem, Andrew J

    2013-02-11

    As successful malaria control programmes move towards elimination, they must identify residual transmission foci, target vector control to high-risk areas, focus on both asymptomatic and symptomatic infections, and manage importation risk. High spatial and temporal resolution maps of malaria risk can support all of these activities, but commonly available malaria maps are based on parasite rate, a poor metric for measuring malaria at extremely low prevalence. New approaches are required to provide case-based risk maps to countries seeking to identify remaining hotspots of transmission while managing the risk of transmission from imported cases. Household locations and travel histories of confirmed malaria patients during 2011 were recorded through routine surveillance by the Swaziland National Malaria Control Programme for the higher transmission months of January to April and the lower transmission months of May to December. Household locations for patients with no travel history to endemic areas were compared against a random set of background points sampled proportionate to population density with respect to a set of variables related to environment, population density, vector control, and distance to the locations of identified imported cases. Comparisons were made separately for the high and low transmission seasons. The Random Forests regression tree classification approach was used to generate maps predicting the probability of a locally acquired case at 100 m resolution across Swaziland for each season. Results indicated that case households during the high transmission season tended to be located in areas of lower elevation, closer to bodies of water, in more sparsely populated areas, with lower rainfall and warmer temperatures, and closer to imported cases than random background points (all p < 0.001). Similar differences were evident during the low transmission season. Maps from the fit models suggested better predictive ability during the high season. Both models proved useful at predicting the locations of local cases identified in 2012. The high-resolution mapping approaches described here can help elimination programmes understand the epidemiology of a disappearing disease. Generating case-based risk maps at high spatial and temporal resolution will allow control programmes to direct interventions proactively according to evidence-based measures of risk and ensure that the impact of limited resources is maximized to achieve and maintain malaria elimination.

  19. Tularemia Outbreak Investigation in Kosovo: Case Control and Environmental Studies

    PubMed Central

    Dedushaj, Isuf; Gjini, Ardiana; Jorgensen, Tine Rikke; Cotter, Benvon; Lieftucht, Alfons; D’Ancona, Fortunato; Dennis, David T.; Kosoy, Michael A.; Mulliqi-Osmani, Gjyle; Grunow, Roland; Kalaveshi, Ariana; Gashi, Luljeta; Humolli, Isme

    2002-01-01

    A large outbreak of tularemia occurred in Kosovo in the early postwar period, 1999-2000. Epidemiologic and environmental investigations were conducted to identify sources of infection, modes of transmission, and household risk factors. Case and control status was verified by enzyme-linked immunosorbent assay, Western blot, and microagglutination assay. A total of 327 serologically confirmed cases of tularemia pharyngitis and cervical lymphadenitis were identified in 21 of 29 Kosovo municipalities. Matched analysis of 46 case households and 76 control households suggested that infection was transmitted through contaminated food or water and that the source of infection was rodents. Environmental circumstances in war-torn Kosovo led to epizootic rodent tularemia and its spread to resettled rural populations living under circumstances of substandard housing, hygiene, and sanitation. PMID:11749751

  20. Exposure to community violence and self-harm in California: A multi-level, population-based, case-control study.

    PubMed

    Matthay, Ellicott C; Farkas, Kriszta; Skeem, Jennifer; Ahern, Jennifer

    2018-06-07

    Self-harm is a leading cause of morbidity and mortality. Exposure to community violence is an important and potentially modifiable feature of the social environment that may affect self-harm, but studies to date are limited in the samples and outcomes examined. We conducted a population-based, nested case-control study. Cases were all deaths and hospital visits due to self-harm in California, 2006-2013. We frequency-matched California resident population-based controls from the American Community Survey to cases on age, gender, race/ethnicity, and year of survey/injury. We assessed past-year community violence using deaths and hospital visits due to interpersonal violence in the community of residence. We estimated risk-difference parameters that were defined to avoid extrapolation and to capture associations between changes in the distribution of community violence and the population-level risk of self-harm. After adjustment for confounders, setting past-year community violence to the lowest monthly levels observed within each community over the study period was associated with a 30.1 (95% CI: 29.6 to 30.5) per 100,000 persons per year lower risk of nonfatal self-harm, but no difference in the risk of fatal self-harm. Associations for a parameter corresponding to a hypothetical violence prevention intervention targeting high-violence communities indicated a 5% decrease in self-harm at the population level. In sensitivity analyses, results were robust. This study strengthens evidence on the relationship between community violence and self-harm. Future research should investigate reasons for differential associations by age and gender and whether community violence prevention programs have meaningful impacts on self-harm.

  1. Epidemiology of haemolytic uremic syndrome in children. Data from the North Italian HUS network.

    PubMed

    Ardissino, Gianluigi; Salardi, Stefania; Colombo, Elisa; Testa, Sara; Borsa-Ghiringhelli, Nicolò; Paglialonga, Fabio; Paracchini, Valentina; Tel, Francesca; Possenti, Ilaria; Belingheri, Mirco; Civitillo, Cristina Felice; Sardini, Stefano; Ceruti, Rossella; Baldioli, Carlo; Tommasi, Paola; Parola, Luciana; Russo, Fiorella; Tedeschi, Silvana

    2016-04-01

    Despite the severity of HUS and the fact that it represents a leading cause of acute kidney injury in children, the general epidemiology of HUS is all but well documented. The present study provides updated, population-based, purely epidemiological information on HUS in childhood from a large and densely populated area of northern Italy (9.6 million inhabitants, 1.6 million children). We systematically reviewed the files concerning patients with STEC-HUS and atypical HUS (aHUS) over a 10-year observation period (January 2003-December 2012). We included all incident cases with a documented first episode of HUS before the age of 18 years. We identified 101 cases of HUS during the 10 years. The overall mean annual incidence was 6.3 cases/million children aged <18 years (range 1.9-11.9), and 15.7/million of age-related population (MARP) among subjects aged <5 years; aHUS accounted for 11.9 % of the cases (mean incidence 0.75/MARP). The overall case fatality rate was 4.0 % (3.4 % STEC-HUS, 8.3 % aHUS). Given the public health impact of HUS, this study provides recent, population-based epidemiological data useful for healthcare planning and particularly for estimating the financial burden that healthcare providers might have to face in treating HUS, whose incidence rate seems to increase in Northern Italy. • HUS is a rare disease, but it represents the leading cause of acute kidney injury in children worldwide. • STEC-HUS (also called typical, D + HUS) is more common compared to atypical HUS, but recent, population-based epidemiological data (incidence) are scanty. What is New: • Comprehensive, population-based epidemiological data concerning both typical and atypical HUS based on a long observational period.

  2. Birth outcomes of cases with isolated atrial septal defect type II--a population-based case-control study.

    PubMed

    Vereczkey, Attila; Kósa, Zsolt; Csáky-Szunyogh, Melinda; Urbán, Róbert; Czeizel, Andrew E

    2013-07-01

    In general, epidemiological studies have evaluated cases with congenital cardiovascular abnormalities together. The aim of this study is to describe the birth outcomes of cases with isolated/single atrial septal defect type II (ASD-II, i.e. only a fossa ovalis defect) after surgical correction or lethal outcome in the light of maternal sociodemographic data. Comparison of birth outcomes and maternal characteristics of cases with ASD-II and controls without defect. The population-based Hungarian Case-Control Surveillance of Congenital Abnormalities. Hungarian newborn infants with or without ASD-II. Medically recorded birth outcomes, maternal age and birth order were evaluated. Marital and employment status was based on maternal information. The lifestyle factors were analyzed in a subsample of mothers visited at home based on a personal interview with mothers and their close relatives, and the family consensus was accepted. Mean gestational age at delivery and birthweight, rate of preterm birth and low birthweight, maternal age, birth order, marital and employment status. The evaluation of 471 cases with ASD-II and 38,151 controls without any defects showed a female excess in cases with ASD-II, having shorter gestational age and lower mean birthweight, and thus a higher rate of preterm births and low birthweight. Intrauterine growth restriction and shorter gestational age were found in cases with ASD-II, particularly in female children. These factors may have a general developmental process in which there was not closure of the foramen ovale, thus echocardiographic screening of these babies might be of value. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

  3. Identification of FGF7 as a novel susceptibility locus for chronic obstructive pulmonary disease.

    PubMed

    Brehm, John M; Hagiwara, Koichi; Tesfaigzi, Yohannes; Bruse, Shannon; Mariani, Thomas J; Bhattacharya, Soumyaroop; Boutaoui, Nadia; Ziniti, John P; Soto-Quiros, Manuel E; Avila, Lydiana; Cho, Michael H; Himes, Blanca; Litonjua, Augusto A; Jacobson, Francine; Bakke, Per; Gulsvik, Amund; Anderson, Wayne H; Lomas, David A; Forno, Erick; Datta, Soma; Silverman, Edwin K; Celedón, Juan C

    2011-12-01

    Traditional genome-wide association studies (GWASs) of large cohorts of subjects with chronic obstructive pulmonary disease (COPD) have successfully identified novel candidate genes, but several other plausible loci do not meet strict criteria for genome-wide significance after correction for multiple testing. The authors hypothesise that by applying unbiased weights derived from unique populations we can identify additional COPD susceptibility loci. Methods The authors performed a homozygosity haplotype analysis on a group of subjects with and without COPD to identify regions of conserved homozygosity haplotype (RCHHs). Weights were constructed based on the frequency of these RCHHs in case versus controls, and used to adjust the p values from a large collaborative GWAS of COPD. The authors identified 2318 RCHHs, of which 576 were significantly (p<0.05) over-represented in cases. After applying the weights constructed from these regions to a collaborative GWAS of COPD, the authors identified two single nucleotide polymorphisms (SNPs) in a novel gene (fibroblast growth factor-7 (FGF7)) that gained genome-wide significance by the false discovery rate method. In a follow-up analysis, both SNPs (rs12591300 and rs4480740) were significantly associated with COPD in an independent population (combined p values of 7.9E-7 and 2.8E-6, respectively). In another independent population, increased lung tissue FGF7 expression was associated with worse measures of lung function. Weights constructed from a homozygosity haplotype analysis of an isolated population successfully identify novel genetic associations from a GWAS on a separate population. This method can be used to identify promising candidate genes that fail to meet strict correction for multiple testing.

  4. New strategies for the management of diverticular disease: insights for the clinician

    PubMed Central

    Floch, Martin

    2013-01-01

    Diverticulosis is one of the most common gastrointestinal conditions affecting the general population in the Western world. It is estimated that over 2.5 million people are affected by diverticular disease in the United States. The spectrum of clinical manifestations of diverticulosis ranges from asymptomatic diverticulosis to complicated diverticulitis. Treatment for symptomatic diverticular disease is largely based on symptoms. Traditional therapy includes fiber, bowel rest, antibiotics, pain control and surgery for selected cases. This review discusses recent advances in the medical treatment of diverticular disease such as the use of mesalamine, rifaximin and probiotics as our understanding of the disease evolves. PMID:23634185

  5. A large community outbreak of blastomycosis in Wisconsin with geographic and ethnic clustering.

    PubMed

    Roy, Monika; Benedict, Kaitlin; Deak, Eszter; Kirby, Miles A; McNiel, Jena T; Sickler, Carrie J; Eckardt, Eileen; Marx, Ruth K; Heffernan, Richard T; Meece, Jennifer K; Klein, Bruce S; Archer, John R; Theurer, Joan; Davis, Jeffrey P; Park, Benjamin J

    2013-09-01

    Blastomycosis is a potentially life-threatening infection caused by the soil-based dimorphic fungus Blastomyces dermatitidis, which is endemic throughout much of the Midwestern United States. We investigated an increase in reported cases of blastomycosis that occurred during 2009-2010 in Marathon County, Wisconsin. Case detection was conducted using the Wisconsin Electronic Disease Surveillance System (WEDSS). WEDSS data were used to compare demographic, clinical, and exposure characteristics between outbreak-related and historical case patients, and to calculate blastomycosis incidence rates. Because initial mapping of outbreak case patients' homes and recreational sites demonstrated unusual neighborhood and household case clustering, we conducted a 1:3 matched case-control study to identify factors associated with being in a geographic cluster. Among the 55 patients with outbreak-related cases, 33 (70%) were hospitalized, 2 (5%) died, 30 (55%) had cluster-related cases, and 20 (45%) were Hmong. The overall incidence increased significantly since 2005 (average 11% increase per year, P < .001), and incidence during 2005-2010 was significantly higher among Asians than non-Asians (2010 incidence: 168 vs 13 per 100 000 population). Thirty of the outbreak cases grouped into 5 residential clusters. Outdoor activities were not risk factors for blastomycosis among cluster case patients or when comparing outbreak cases to historical cases. This outbreak of blastomycosis, the largest ever reported, was characterized by unique household and neighborhood clustering likely related to multifocal environmental sources. The reasons for the large number of Hmong affected are unclear, but may involve genetic predisposition.

  6. Metformin for Primary Colorectal Cancer Prevention in Diabetic Patients: A Case-Control Study in a US Population

    PubMed Central

    Sehdev, Amikar; Shih, Ya-Chen T.; Vekhter, Benjamin; Bissonnette, Marc; Olopade, Olufunmilayo I.; Polite, Blase

    2016-01-01

    Background Emerging evidence from observational studies suggests that metformin may be beneficial in the primary prevention of colorectal cancer (CRC). However, none of these were conducted in a US population. Since environmental factors, such as Western diet and obesity, are implicated in the causation of CRC, we conducted a large case control study to assess the effects of metformin on CRC incidence in a US population. Methods MarketScan® databases were used to identify diabetic patients with CRC. A case was defined as having an incident diagnosis of CRC. Up to two controls matched for age, sex and geographical region, were selected for each case. Metformin exposure was assessed by prescription tracking in the 12 months period prior to the index date. Conditional logistic regression was used to adjust for multiple potential confounders and to calculate adjusted odds ratios (AOR). Results The mean age of participants was 55 and 57 years in the control and case group, respectively (p=1.0). Sixty percent of the study participants were males and 40% were females in each group. In the multivariable model, any metformin use was associated with 15% reduced odds of CRC (AOR, 0.85, 95% confidence interval (CI), 0.76–0.95, p<0.007). After adjusting for health-care utilization the beneficial effect of metformin was reduced to 12% (AOR, 0.88, 95% CI, 0.77–1.00, p=0.05). The dose-response analyses showed no significant association with metformin dose, duration or total exposure. Conclusions Metformin use is associated with reduced risk of developing CRC among diabetic patients in the US population. PMID:25424411

  7. Does Marital Status Predict the Odds of Suicidal Death in Taiwan? A Seven-Year Population-Based Study

    ERIC Educational Resources Information Center

    Yeh, Jui-Yuan; Xirasagar, Sudha; Liu, Tsai-Ching; Li, Chong-Yi; Lin, Herng-Ching

    2008-01-01

    Using nationwide, 7-year population-based data for 1997-2003, we examined marital status to see if it predicted suicide among the ethnic Chinese population of Taiwan. Using cause of death data, with a case-control design, two groups--total adult suicide deaths, n = 17,850, the study group, and adult deaths other than suicide, n = 71,400 (randomly…

  8. Childhood hematologic cancer and residential proximity to oil and gas development.

    PubMed

    McKenzie, Lisa M; Allshouse, William B; Byers, Tim E; Bedrick, Edward J; Serdar, Berrin; Adgate, John L

    2017-01-01

    Oil and gas development emits known hematological carcinogens, such as benzene, and increasingly occurs in residential areas. We explored whether residential proximity to oil and gas development was associated with risk for hematologic cancers using a registry-based case-control study design. Participants were 0-24 years old, living in rural Colorado, and diagnosed with cancer between 2001-2013. For each child in our study, we calculated inverse distance weighted (IDW) oil and gas well counts within a 16.1-kilometer radius of residence at cancer diagnosis for each year in a 10 year latency period to estimate density of oil and gas development. Logistic regression, adjusted for age, race, gender, income, and elevation was used to estimate associations across IDW well count tertiles for 87 acute lymphocytic leukemia (ALL) cases and 50 non-Hodgkin lymphoma (NHL) cases, compared to 528 controls with non-hematologic cancers. Overall, ALL cases 0-24 years old were more likely to live in the highest IDW well count tertiles compared to controls, but findings differed substantially by age. For ages 5-24, ALL cases were 4.3 times as likely to live in the highest tertile, compared to controls (95% CI: 1.1 to 16), with a monotonic increase in risk across tertiles (trend p-value = 0.035). Further adjustment for year of diagnosis increased the association. No association was found between ALL for children aged 0-4 years or NHL and IDW well counts. While our study benefited from the ability to select cases and controls from the same population, use of cancer-controls, the limited number of ALL and NHL cases, and aggregation of ages into five year ranges, may have biased our associations toward the null. In addition, absence of information on O&G well activities, meteorology, and topography likely reduced temporal and spatial specificity in IDW well counts. Because oil and gas development has potential to expose a large population to known hematologic carcinogens, further study is clearly needed to substantiate both our positive and negative findings. Future studies should incorporate information on oil and gas development activities and production levels, as well as levels of specific pollutants of interest (e.g. benzene) near homes, schools, and day care centers; provide age-specific residential histories; compare cases to controls without cancer; and address other potential confounders, and environmental stressors.

  9. Polymorphisms in CTNNBL1 in relation to colorectal cancer with evolutionary implications

    PubMed Central

    Huhn, Stefanie; Ingelfinger, Dierk; Bermejo, Justo Lorenzo; Bevier, Melanie; Pardini, Barbara; Naccarati, Alessio; Steinke, Verena; Rahner, Nils; Holinski-Feder, Elke; Morak, Monika; Schackert, Hans K; Görgens, Heike; Pox, Christian P; Goecke, Timm; Kloor, Matthias; Loeffler, Markus; Büttner, Reinhard; Vodickova, Ludmila; Novotny, Jan; Demir, Kubilay; Cruciat, Cristina-Maria; Renneberg, Rebecca; Huber, Wolfgang; Niehrs, Christof; Boutros, Michael; Propping, Peter; Vodička, Pavel; Hemminki, Kari; Försti, Asta

    2011-01-01

    Colorectal cancer (CRC) is a complex disease related to environmental and genetic risk factors. Several studies have shown that susceptibility to complex diseases can be mediated by ancestral alleles. Using RNAi screening, CTNNBL1 was identified as a putative regulator of the Wnt signaling pathway, which plays a key role in colorectal carcinogenesis. Recently, single nucleotide polymorphisms (SNPs) in CTNNBL1 have been associated with obesity, a known risk factor for CRC. We investigated whether genetic variation in CTNNBL1 affects susceptibility to CRC and tested for signals of recent selection. We applied a tagging SNP approach that cover all known common variation in CTNNBL1 (allele frequency >5%; r2>0.8). A case-control study was carried out using two well-characterized study populations: a hospital-based Czech population composed of 751 sporadic cases and 755 controls and a family/early onset-based German population (697 cases and 644 controls). Genotyping was performed using allele specific PCR based TaqMan® assays (Applied Biosystems, Weiterstadt, Germany). In the Czech cohort, containing sporadic cases, the ancestral alleles of three SNPs showed evidence of association with CRC: rs2344481 (OR 1.44, 95%CI 1.06-1.95, dominant model), rs2281148 (OR 0.59, 95%CI 0.36-0.96, dominant model) and rs2235460 (OR 1.38, 95%CI 1.01-1.89, AA vs. GG). The associations were less prominent in the family/early onset-based German cohort. Data derived from several databases and statistical tests consistently pointed to a likely shaping of CTNNBL1 by positive selection. Further studies are needed to identify the actual function of CTNNBL1 and to validate the association results in other populations. PMID:21537400

  10. Possible association between hyperthyroidism in pregnant women and obstructive congenital abnormalities of urinary tract in their offspring--a population-based case-control study.

    PubMed

    Bánhidy, Ferenc; Puhó, Erzsébet H; Czeizel, Andrew E

    2011-02-01

    The teratogenic potential of some antithyroid drugs is known, but the aim of the study was to estimate the risk of congenital abnormalities (CAs) in the offspring of pregnant women with hyperthyroidism with or without antithyroid drug treatment. Comparison of the occurrence of medically recorded hyperthyroidism who had malformed fetuses/newborns (cases) and who delivered healthy babies (controls) in the population-based Hungarian Case-Control Surveillance System of CAs, 1980-1996. Of 22,843 cases with congenital abnormalities, 71 (0.31%) while of 38,151 controls, 116 (0.30%) had mothers with hyperthyroidism. The rate of hyperthyroidism in the mothers of cases with different CAs and in the mothers of matched controls was compared. Preeclampsia-eclampsia occurred more frequently in pregnant women with hyperthyroidism without antithyroid treatment. The analysis of specific groups of CAs showed an association between hyperthyroidism in pregnant women and obstructive defects of urinary tract in their children. The lack of appropriate treatment of pregnant women affected with hyperthyroidism seems to be the major problem, because it would be necessary to prevent the hyperthyroidism related risks of pregnancy complications and CAs which exceed the risk of antithyroid medication in these pregnant women.

  11. Occupational exposure to petroleum-based and oxygenated solvents and hypopharyngeal and laryngeal cancer in France: the ICARE study.

    PubMed

    Barul, Christine; Carton, Matthieu; Radoï, Loredana; Menvielle, Gwenn; Pilorget, Corinne; Bara, Simona; Stücker, Isabelle; Luce, Danièle

    2018-04-05

    To examine associations between occupational exposure to petroleum-based and oxygenated solvents and the risk of hypopharyngeal and laryngeal cancer. ICARE is a large, frequency-matched population-based case-control study conducted in France. Lifetime occupational history, tobacco smoking and alcohol consumption were collected. Analyses were restricted to men and included 383 cases of hypopharyngeal cancer, 454 cases of laryngeal cancer, and 2780 controls. Job-exposure matrices were used to assess exposure to five petroleum-based solvents (benzene; gasoline; white spirits; diesel, fuels and kerosene; special petroleum products) and to five oxygenated solvents (alcohols; ketones and esters; ethylene glycol; diethyl ether; tetrahydrofuran). Odds ratios (ORs) adjusted for smoking, alcohol drinking and other potential confounders and 95% confidence intervals (CI) were estimated with unconditional logistic models. No significant association was found between hypopharyngeal or laryngeal cancer risk and exposure to the solvents under study. Non-significantly elevated risks of hypopharyngeal cancer were found in men exposed to high cumulative levels of white spirits (OR = 1.46; 95% CI: 0.88-2.43) and tetrahydrofuran (OR = 2.63; 95CI%: 0.55-12.65), with some indication of a dose-response relationship (p for trend: 0.09 and 0.07 respectively). This study provides weak evidence for an association between hypopharyngeal cancer and exposure to white spirits and tetrahydrofuran, and overall does not suggest a substantial role of exposure to petroleum-based or oxygenated solvents in hypopharyngeal or laryngeal cancer risk.

  12. Clinical features of Hispanic thyroid cancer cases and the role of known genetic variants on disease risk

    PubMed Central

    Estrada-Florez, Ana P.; Bohórquez, Mabel E.; Sahasrabudhe, Ruta; Prieto, Rodrigo; Lott, Paul; Duque, Carlos S.; Donado, Jorge; Mateus, Gilbert; Bolaños, Fernando; Vélez, Alejandro; Echeverry, Magdalena; Carvajal-Carmona, Luis G.

    2016-01-01

    Abstract Thyroid cancer (TC) is the second most common cancer among Hispanic women. Recent genome-wide association (GWA) and candidate studies identified 6 single nucleotide polymorphisms (SNPs; rs966423, rs2439302, rs965513, rs6983267, rs944289, and rs116909374), associated with increased TC risk in Europeans but their effects on disease risk have not been comprehensively tested in Hispanics. In this study, we aimed to describe the main clinicopathological manifestations and to evaluate the effects of known SNPs on TC risk and on clinicopathological manifestations in a Hispanic population. We analyzed 281 nonmedullary TC cases and 1146 cancer-free controls recruited in a multicenter population-based study in Colombia. SNPs were genotyped by Kompetitive allele specific polymerase chain reaction (KASP) technique. Association between genetic variants and TC risk was assessed by computing odds ratios (OR) and confidence intervals (CIs). Consistent with published data in U.S. Hispanics, our cases had a high prevalence of large tumors (>2 cm, 43%) and a high female/male ratio (5:1). We detected significant associations between TC risk and rs965513A (OR = 1.41), rs944289T (OR = 1.26), rs116909374A (OR = 1.96), rs2439302G (OR = 1.19), and rs6983267G (OR = 1.18). Cases carried more risk alleles than controls (5.16 vs. 4.78, P = 4.8 × 10−6). Individuals with ≥6 risk alleles had >6-fold increased TC risk (OR = 6.33, P = 4.0 × 10−6) compared to individuals with ≤2 risk alleles. rs944289T and rs116909374A were strongly associated with follicular histology (ORs = 1.61 and 3.33, respectively); rs2439302G with large tumors (OR = 1.50); and rs965513A with regional disease (OR = 1.92). To our knowledge, this is the first study of known TC risk variants in South American Hispanics and suggests that they increase TC susceptibility in this population and can identify patients at higher risk of severe disease. PMID:27512836

  13. Clinical features of Hispanic thyroid cancer cases and the role of known genetic variants on disease risk.

    PubMed

    Estrada-Florez, Ana P; Bohórquez, Mabel E; Sahasrabudhe, Ruta; Prieto, Rodrigo; Lott, Paul; Duque, Carlos S; Donado, Jorge; Mateus, Gilbert; Bolaños, Fernando; Vélez, Alejandro; Echeverry, Magdalena; Carvajal-Carmona, Luis G

    2016-08-01

    Thyroid cancer (TC) is the second most common cancer among Hispanic women. Recent genome-wide association (GWA) and candidate studies identified 6 single nucleotide polymorphisms (SNPs; rs966423, rs2439302, rs965513, rs6983267, rs944289, and rs116909374), associated with increased TC risk in Europeans but their effects on disease risk have not been comprehensively tested in Hispanics. In this study, we aimed to describe the main clinicopathological manifestations and to evaluate the effects of known SNPs on TC risk and on clinicopathological manifestations in a Hispanic population.We analyzed 281 nonmedullary TC cases and 1146 cancer-free controls recruited in a multicenter population-based study in Colombia. SNPs were genotyped by Kompetitive allele specific polymerase chain reaction (KASP) technique. Association between genetic variants and TC risk was assessed by computing odds ratios (OR) and confidence intervals (CIs).Consistent with published data in U.S. Hispanics, our cases had a high prevalence of large tumors (>2 cm, 43%) and a high female/male ratio (5:1). We detected significant associations between TC risk and rs965513A (OR = 1.41), rs944289T (OR = 1.26), rs116909374A (OR = 1.96), rs2439302G (OR = 1.19), and rs6983267G (OR = 1.18). Cases carried more risk alleles than controls (5.16 vs. 4.78, P = 4.8 × 10). Individuals with ≥6 risk alleles had >6-fold increased TC risk (OR = 6.33, P = 4.0 × 10) compared to individuals with ≤2 risk alleles. rs944289T and rs116909374A were strongly associated with follicular histology (ORs = 1.61 and 3.33, respectively); rs2439302G with large tumors (OR = 1.50); and rs965513A with regional disease (OR = 1.92).To our knowledge, this is the first study of known TC risk variants in South American Hispanics and suggests that they increase TC susceptibility in this population and can identify patients at higher risk of severe disease.

  14. Risk of intracerebral hemorrhage associated with phenprocoumon exposure: a nested case-control study in a large population-based German database.

    PubMed

    Behr, Sigrid; Andersohn, Frank; Garbe, Edeltraut

    2010-07-01

    Intracerebral hemorrhage (ICH) is the most serious complication of oral anticoagulation. This study investigated the risk of ICH for phenprocoumon which is the most widely used oral anticoagulant in Germany. We conducted a nested case-control study in a cohort of 13.4 million insurants of 4 German statutory health insurances (SHIs) who were continuously enrolled for 6 months prior to cohort entry. Cases were patients hospitalized for ICH. Ten controls were matched to each case by SHI, birth year, and sex using incidence density sampling. Rate ratios (RR) of ICH for current phenprocoumon use as compared to non-use were estimated from odds ratios calculated by conditional logistic regression analyses considering multiple risk factors. Analysis of the full cohort revealed a strong increase in incidence of ICH with increasing age. In the nested case-control study including 8138 cases of ICH and 81,373 matched controls, we observed an increased risk of ICH for current phenprocoumon exposure that varied with age. The phenprocoumon-associated risk of ICH was lower in older age groups with RRs from 4.20 (95% confidence interval (CI) 2.44-7.21) for phenprocoumon users less than 55 years of age to 2.43 (95%CI, 1.81-3.27) for those older than 85 years. Our study confirmed known risk factors of ICH. Phenprocoumon exposure was associated with an increased risk of ICH. The interaction of risk for phenprocoumon with age was unexpected and needs further study. (c) 2010 John Wiley & Sons, Ltd.

  15. Measles outbreak in the Republic of the Marshall Islands, 2003.

    PubMed

    Hyde, Terri B; Dayan, Gustavo H; Langidrik, Justina R; Nandy, Robin; Edwards, Russell; Briand, Kennar; Konelios, Mailynn; Marin, Mona; Nguyen, Huong Q; Khalifah, Anthony P; O'leary, Michael J; Williams, Nobia J; Bellini, William J; Bi, Daoling; Brown, Cedric J; Seward, Jane F; Papania, Mark J

    2006-04-01

    Measles is a highly contagious viral infection. Measles transmission can be prevented through high population immunity (>or=95%) achieved by measles vaccination. In the Republic of the Marshall Islands (RMI), no measles cases were reported during 1989-2002; however, a large measles outbreak occurred in 2003. Reported 1-dose measles vaccine coverage among children aged 12-23 months varied widely (52-94%) between 1990 and 2000. RMI is a Pacific island nation (1999 population: 50,840). A measles case was defined as fever, rash, and cough, or coryza, or conjunctivitis, in an RMI resident between July 13 and November 7, 2003. A vaccination campaign was used for outbreak control. Of the 826 reported measles cases, 766 (92%) occurred in the capital (Majuro). There were 186 (23%) cases in infants aged <1 year and 309 (37%) of cases in persons aged >or=15 years. The attack rate was highest among infants (Majuro atoll: 213 cases/1,000 infants). Among cases aged 1-14 years, 281 (59%) reported no measles vaccination before July 2003. There were 100 hospitalizations and 3 deaths. The measles H1 genotype was identified. The vaccination campaign resulted in 93% coverage among persons aged 6 months to 40 years. Interpretation Populations without endemic measles transmission can accumulate substantial susceptibility and be at risk for large outbreaks when measles virus is imported. 'Islands' of measles susceptibility may develop in infants, adults, and any groups with low vaccine coverage. To prevent outbreaks, high population immunity must be sustained by maintaining and documenting high vaccine coverage.

  16. Socioeconomic status is associated with symptom severity and sickness absence in people with infectious intestinal disease in the UK.

    PubMed

    Rose, Tanith C; Adams, Natalie L; Barr, Benjamin; Hawker, Jeremy; O'Brien, Sarah J; Violato, Mara; Whitehead, Margaret; Taylor-Robinson, David C

    2017-06-23

    The burden of infectious intestinal disease (IID) in the UK is substantial. Negative consequences including sickness absence are common, but little is known about the social patterning of these outcomes, or the extent to which they relate to disease severity. We performed a cross-sectional analysis using IID cases identified from a large population-based survey, to explore the association between socioeconomic status (SES) and symptom severity and sickness absence; and to assess the role of symptom severity on the relationship between SES and absence. Regression modelling was used to investigate these associations, whilst controlling for potential confounders such as age, sex and ethnicity. Among 1164 cases, those of lower SES versus high had twice the odds of experiencing severe symptoms (OR 2.2, 95%CI;1.66-2.87). Lower SES was associated with higher odds of sickness absence (OR 1.8, 95%CI;1.26-2.69), however this association was attenuated after adjusting for symptom severity (OR 1.4, 95%CI;0.92-2.07). In a large sample of IID cases, those of low SES versus high were more likely to report severe symptoms, and sickness absence; with greater severity largely explaining the higher absence. Public health interventions are needed to address the unequal consequences of IID identified.

  17. Characterizing a large outbreak of dengue fever in Guangdong Province, China.

    PubMed

    Xiao, Jian-Peng; He, Jian-Feng; Deng, Ai-Ping; Lin, Hua-Liang; Song, Tie; Peng, Zhi-Qiang; Wu, Xiao-Cheng; Liu, Tao; Li, Zhi-Hao; Rutherford, Shannon; Zeng, Wei-Lin; Li, Xing; Ma, Wen-Jun; Zhang, Yong-Hui

    2016-05-03

    Dengue cases have been reported each year for the past 25 years in Guangdong Province, China with a recorded historical peak in 2014. This study aims to describe the epidemiological characteristics of this large outbreak in order to better understand its epidemic factors and to inform control strategies. Data for clinically diagnosed and laboratory-confirmed dengue fever cases in 2014 were extracted from the China Notifiable Infectious Disease Reporting System. We analyzed the incidence and characteristics of imported and indigenous cases in terms of population, temporal and spatial distributions. A total of 45 224 dengue fever cases and 6 deaths were notified in Guangdong Province in 2014, with an incidence of 47.3 per 100 000 people. The elderly (65+ years) represented 11.7 % of total indigenous cases with the highest incidence (72.3 per 100 000). Household workers and the unemployed accounted for 23.1 % of indigenous cases. The majority of indigenous cases occurred in the 37(th) to 44(th) week of 2014 (September and October) and almost all (20 of 21) prefecture-level cities in Guangdong were affected. Compared to the non-Pearl River Delta Region, the Pearl River Delta Region accounted for the majority of dengue cases and reported cases earlier in 2014. Dengue virus serotypes 1 (DENV-1), 2 (DENV-2) and 3 (DENV-3) were detected and DENV-1 was predominant (88.4 %). Dengue fever is a serious public health problem and is emerging as a continuous threat in Guangdong Province. There is an urgent need to enhance dengue surveillance and control, especially for the high-risk populations in high-risk areas.

  18. Prevalence of oral HPV infection among healthy individuals and head and neck cancer cases in the French West Indies.

    PubMed

    Auguste, Aviane; Gaëte, Stanie; Herrmann-Storck, Cécile; Michineau, Leah; Joachim, Clarisse; Deloumeaux, Jacqueline; Duflo, Suzy; Luce, Danièle

    2017-11-01

    Human papillomavirus (HPV) is known to play a role in the development of head and neck squamous cell carcinomas (HNSCC) and to date, no study has reported on the association between oral HPV infection and HNSCC in the Caribbean. The objective was to determine the prevalence of oral HPV infection in the French West Indies (FWI), overall and by HPV genotype, among HNSCC cases and healthy population controls. We used data from a population-based case-control study conducted in the FWI. The prevalence of oral HPV was estimated separately among 100 HNSCC cases (mean age 59 years) and 308 population controls (mean age 57 years). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using a logistic regression adjusting for age, sex, tobacco, and alcohol consumption, to assess the association between oral HPV infection and HNSCC. Prevalence of oral HPV infections was 26% in controls (30% in men and 14% in women) and 36% in HNSCC cases (36% in men, 33% in women). HPV52 was the most commonly detected genotype, in cases and in controls. The prevalence of HPV16, HPV33, and HPV51 was significantly higher in cases than in controls (p = 0.0340, p = 0.0472, and 0.0144, respectively). Oral infection with high-risk HPV was associated with an increase in risk of HNSCC (OR 1.99, 95% CI 0.95-4.15). HPV16 was only associated with oropharyngeal cancer (OR 16.01, 95% CI 1.67-153.64). This study revealed a high prevalence of oral HPV infection in this middle-aged Afro-Caribbean population, and a specific distribution of HPV genotypes. These findings may provide insight into HNSCC etiology specific to the FWI.

  19. Possible association between ocular chloramphenicol and aplastic anaemia—the absolute risk is very low

    PubMed Central

    Laporte, Joan-Ramon; Vidal, Xavier; Ballarín, Elena; Ibáñez, Luisa

    1998-01-01

    Aims To determine whether topical ocular chloramphenicol increases the risk of aplastic anaemia and to estimate the magnitude of this risk, if any. Methods Population-based prospective case-control surveillance of aplastic anaemia in a community of 4.2 million inhabitants from 1980 to 1995 (67.2 million person-years) plus case-population estimate of the risk, based on sales figures of ocular chloramphenicol in the study area during the study period. Results One hundred and forty-five patients with aplastic anaemia and 1,226 controls were included in the analysis. Three cases (2.1%) and 5 controls (0.4%) had been exposed to ocular chloramphenicol during the relevant etiological period. The adjusted odds ratio was 3.77 (95% confidence interval, 0.84–16.90). Two cases had also been exposed to other known causes of aplastic anaemia. The incidence of aplastic anaemia among users of ocular chloramphenicol was 0.36 cases per million weeks of treatment. The incidence among non users was 0.04 cases per million weeks. Conclusions An association between ocular chloramphenicol and aplastic anaemia cannot be excluded. However, the risk is less than one per million treatment courses. PMID:9723830

  20. White Matter Correlates of Musical Anhedonia: Implications for Evolution of Music.

    PubMed

    Loui, Psyche; Patterson, Sean; Sachs, Matthew E; Leung, Yvonne; Zeng, Tima; Przysinda, Emily

    2017-01-01

    Recent theoretical advances in the evolution of music posit that affective communication is an evolutionary function of music through which the mind and brain are transformed. A rigorous test of this view should entail examining the neuroanatomical mechanisms for affective communication of music, specifically by comparing individual differences in the general population with a special population who lacks specific affective responses to music. Here we compare white matter connectivity in BW, a case with severe musical anhedonia, with a large sample of control subjects who exhibit normal variability in reward sensitivity to music. We show for the first time that structural connectivity within the reward system can predict individual differences in musical reward in a large population, but specific patterns in connectivity between auditory and reward systems are special in an extreme case of specific musical anhedonia. Results support and extend the Mixed Origins of Music theory by identifying multiple neural pathways through which music might operate as an affective signaling system.

  1. White Matter Correlates of Musical Anhedonia: Implications for Evolution of Music

    PubMed Central

    Loui, Psyche; Patterson, Sean; Sachs, Matthew E.; Leung, Yvonne; Zeng, Tima; Przysinda, Emily

    2017-01-01

    Recent theoretical advances in the evolution of music posit that affective communication is an evolutionary function of music through which the mind and brain are transformed. A rigorous test of this view should entail examining the neuroanatomical mechanisms for affective communication of music, specifically by comparing individual differences in the general population with a special population who lacks specific affective responses to music. Here we compare white matter connectivity in BW, a case with severe musical anhedonia, with a large sample of control subjects who exhibit normal variability in reward sensitivity to music. We show for the first time that structural connectivity within the reward system can predict individual differences in musical reward in a large population, but specific patterns in connectivity between auditory and reward systems are special in an extreme case of specific musical anhedonia. Results support and extend the Mixed Origins of Music theory by identifying multiple neural pathways through which music might operate as an affective signaling system. PMID:28993748

  2. Risk of stomach cancer in Aotearoa/New Zealand: A Māori population based case-control study

    PubMed Central

    Sporle, Andrew; Corbin, Marine; Cheng, Soo; Harawira, Pauline; Gray, Michelle; Whaanga, Tracey; Guilford, Parry; Koea, Jonathan; Pearce, Neil

    2017-01-01

    Māori, the indigenous people of New Zealand, experience disproportionate rates of stomach cancer, compared to non-Māori. The overall aim of the study was to better understand the reasons for the considerable excess of stomach cancer in Māori and to identify priorities for prevention. Māori stomach cancer cases from the New Zealand Cancer Registry between 1 February 2009 and 31 October 2013 and Māori controls, randomly selected from the New Zealand electoral roll were matched by 5-year age bands to cases. Logistic regression was used to estimate odd ratios (OR) and 95% confidence intervals (CI) between exposures and stomach cancer risk. Post-stratification weighting of controls was used to account for differential non-response by deprivation category. The study comprised 165 cases and 480 controls. Nearly half (47.9%) of cases were of the diffuse subtype. There were differences in the distribution of risk factors between cases and controls. Of interest were the strong relationships seen with increased stomach risk and having >2 people sharing a bedroom in childhood (OR 3.30, 95%CI 1.95–5.59), testing for H pylori (OR 12.17, 95%CI 6.15–24.08), being an ex-smoker (OR 2.26, 95%CI 1.44–3.54) and exposure to environmental tobacco smoke in adulthood (OR 3.29, 95%CI 1.94–5.59). Some results were attenuated following post-stratification weighting. This is the first national study of stomach cancer in any indigenous population and the first Māori-only population-based study of stomach cancer undertaken in New Zealand. We emphasize caution in interpreting the findings given the possibility of selection bias. Population-level strategies to reduce the incidence of stomach cancer in Māori include expanding measures to screen and treat those infected with H pylori and a continued policy focus on reducing tobacco consumption and uptake. PMID:28732086

  3. Occupational exposure to lead and lung cancer: results from two case-control studies in Montreal, Canada.

    PubMed

    Wynant, Willy; Siemiatycki, Jack; Parent, Marie-Élise; Rousseau, Marie-Claude

    2013-03-01

    We investigated the association between workplace lead exposure and lung cancer risk, separately for organic lead and for inorganic lead, from either engine emissions or from other sources. Two population-based case-control studies were carried out in Montreal (1979-1986 and 1996-2002) to investigate occupational factors in relation to lung cancer among 1593 men with histologically confirmed incident lung cancer, and 1426 controls from the general population. Interviews elicited information on sociodemographic characteristics, lifetime smoking and occupational history. Chemists translated each job into potential chemical exposures. Cumulative indices of exposure were derived and classified into non-substantial and substantial exposure. ORs adjusted for several potential confounders including smoking, and 95% CIs were estimated by logistic regression. Lifetime prevalences of exposure in Study I were 3% for organic lead, 40% for inorganic lead from engine emissions and 17% for inorganic lead from other sources; corresponding prevalences in Study II were 4%, 19% and 16%, respectively. No associations were observed when comparing ever to never exposed subjects in pooled analyses (organic lead, OR=1.39, 95% CI 0.77 to 2.52; inorganic lead from engine emissions: OR=0.89, 95% CI 0.72 to 1.09; inorganic lead from other sources: OR=0.99, 95% CI 0.76 to 1.29). Nor were these exposures associated with lung cancer in subjects with substantial cumulative exposure. In this large study, using a blinded expert-based assessment of lifetime occupational exposure and adjustment for several potential confounders, we observed no increased risk of lung cancer with exposure to lead compounds.

  4. Exposure to genocide and risk of suicide in Rwanda: a population-based case–control study

    PubMed Central

    Rubanzana, Wilson; Hedt-Gauthier, Bethany L; Ntaganira, Joseph; Freeman, Michael D

    2015-01-01

    Background In Rwanda, an estimated one million people were killed during the 1994 genocide, leaving the country shattered and social fabric destroyed. Large-scale traumatic events such as wars and genocides have been linked to endemic post-traumatic stress disorder, depression and suicidality. The study objective was to investigate whether the 1994 genocide exposure is associated with suicide in Rwanda. Methods We conducted a population-based case–control study. Suicide victims were matched to three living controls for sex, age and residential location. Exposure was defined as being a genocide survivor, having suffered physical/sexual abuse in the genocide, losing a first-degree relative in the genocide, having been convicted for genocide crimes or having a first-degree relative convicted for genocide. From May 2011 to May 2013, 162 cases and 486 controls were enrolled countrywide. Information was collected from the police, local village administrators and family members. Results After adjusting for potential confounders, having been convicted for genocide crimes was a significant predictor for suicide (OR=17.3, 95% CI 3.4 to 88.1). Being a survivor, having been physically or sexually abused during the genocide, and having lost a first-degree family member to genocide were not significantly associated with suicide. Conclusions These findings demonstrate that individuals convicted for genocide crimes are experiencing continued psychological disturbances that affect their social reintegration into the community even 20 years after the event. Given the large number of genocide perpetrators reintegrated after criminal courts and Gacaca traditional reconciling trials, suicide could become a serious public health burden if preventive remedial action is not identified. PMID:25488977

  5. Evidence of Recessive Alzheimer Disease Loci in a Caribbean Hispanic Data Set

    PubMed Central

    Ghani, Mahdi; Sato, Christine; Lee, Joseph H.; Reitz, Christiane; Moreno, Danielle; Mayeux, Richard; St George-Hyslop, Peter; Rogaeva, Ekaterina

    2014-01-01

    IMPORTANCE The search for novel Alzheimer disease (AD) genes or pathologic mutations within known AD loci is ongoing. The development of array technologies has helped to identify rare recessive mutations among long runs of homozygosity (ROHs), in which both parental alleles are identical. Caribbean Hispanics are known to have an elevated risk for AD and tend to have large families with evidence of inbreeding. OBJECTIVE To test the hypothesis that the late-onset AD in a Caribbean Hispanic population might be explained in part by the homozygosity of unknown loci that could harbor recessive AD risk haplotypes or pathologic mutations. DESIGN We used genome-wide array data to identify ROHs (>1 megabase) and conducted global burden and locus-specific ROH analyses. SETTING A whole-genome case-control ROH study. PARTICIPANTS A Caribbean Hispanic data set of 547 unrelated cases (48.8% with familial AD) and 542 controls collected from a population known to have a 3-fold higher risk of AD vs non-Hispanics in the same community. Based on a Structure program analysis, our data set consisted of African Hispanic (207 cases and 192 controls) and European Hispanic (329 cases and 326 controls) participants. EXPOSURE Alzheimer disease risk genes. MAIN OUTCOMES AND MEASURES We calculated the total and mean lengths of the ROHs per sample. Global burden measurements among autosomal chromosomes were investigated in cases vs controls. Pools of overlapping ROH segments (consensus regions) were identified, and the case to control ratio was calculated for each consensus region. We formulated the tested hypothesis before data collection. RESULTS In total, we identified 17 137 autosomal regions with ROHs. The mean length of the ROH per person was significantly greater in cases vs controls (P = .0039), and this association was stronger with familial AD (P = .0005). Among the European Hispanics, a consensus region at the EXOC4 locus was significantly associated with AD even after correction for multiple testing (empirical P value 1 [EMP1], .0001; EMP2, .002; 21 AD cases vs 2 controls). Among the African Hispanic subset, the most significant but nominal association was observed for CTNNA3, a well-known AD gene candidate (EMP1, .002; 10 AD cases vs 0 controls). CONCLUSIONS AND RELEVANCE Our results show that ROHs could significantly contribute to the etiology of AD. Future studies would require the analysis of larger, relatively inbred data sets that might reveal novel recessive AD genes. The next step is to conduct sequencing of top significant loci in a subset of samples with overlapping ROHs. PMID:23978990

  6. Cadmium exposure and risk of lung cancer: a meta-analysis of cohort and case-control studies among general and occupational populations.

    PubMed

    Chen, Cheng; Xun, Pengcheng; Nishijo, Muneko; He, Ka

    2016-09-01

    The association between cadmium exposure and risk of lung cancer is still unclear. We quantitatively reviewed the observational studies that investigated the association between cadmium exposure and lung cancer risk in both general and occupational populations published through April 2015. The final data set is comprised of three cohort studies in the general population totaling 22,551 participants (354 events) with a mean follow-up of 15 years, five occupational cohort studies including 4205 individuals (180 events) with an average follow-up of 31 years, and three occupational case-control studies including 4740 cases and 6268 controls. Comparing the highest to the lowest category of cadmium exposure, the weighted relative risk and 95% confidence interval of lung cancer in the general population was 1.42 (95% CI (0.91, 2.23)); the weighted risk estimates (95% CIs) of lung cancer in three occupational cohort studies and three case-control studies were 0.68 (95% CI (0.33, 1.41)) and 1.61 (95% CI (0.94, 2.75)), respectively. No linear association was found. When comparing participants exposed to cadmium with non-exposed based on available data, the association became statistically significant. According to findings from this meta-analysis, the possibility that cadmium exposure may increase risk of lung cancer cannot be completely ruled out in either general or occupational population.

  7. Prenatal Maternal Serum Concentrations of Per- and Polyfluoroalkyl Substances in Association with Autism Spectrum Disorder and Intellectual Disability.

    PubMed

    Lyall, Kristen; Yau, Vincent M; Hansen, Robin; Kharrazi, Martin; Yoshida, Cathleen K; Calafat, Antonia M; Windham, Gayle; Croen, Lisa A

    2018-01-02

    Emerging work has examined neurodevelopmental outcomes following prenatal exposure to per- and polyfluoroalkyl substances (PFAS), but few studies have assessed associations with autism spectrum disorder (ASD). Our objective was to estimate associations of maternal prenatal PFAS concentrations with ASD and intellectual disability (ID) in children. Participants were from a population-based nested case-control study of children born from 2000 to 2003 in southern California, including children diagnosed with ASD ( n =553), ID without autism ( n =189), and general population (GP) controls ( n =433). Concentrations of eight PFAS from stored maternal sera collected at 15-19 wk gestational age were quantified and compared among study groups. We used logistic regression to obtain adjusted odds ratios for the association between prenatal PFAS concentrations (parameterized continuously and as quartiles) and ASD versus GP controls, and separately for ID versus GP controls. Geometric mean concentrations of most PFAS were lower in ASD and ID groups relative to GP controls. ASD was not significantly associated with prenatal concentrations of most PFAS, though significant inverse associations were found for perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) [adjusted ORs for the highest vs. lowest quartiles 0.62 (95% CI: 0.41, 0.93) and 0.64 (95% CI: 0.43, 0.97), respectively]. Results for ID were similar. Results from this large case-control study with prospectively collected prenatal measurements do not support the hypothesis that prenatal exposure to PFAS is positively associated with ASD or ID. https://doi.org/10.1289/EHP1830.

  8. Impacts from control operations on a recreationally hunted feral swine population at a large military installation in Florida.

    PubMed

    Engeman, Richard; Hershberger, Troy; Orzell, Steve; Felix, Rodney; Killian, Gary; Woolard, John; Cornman, Jon; Romano, David; Huddleston, Chet; Zimmerman, Pat; Barre, Chris; Tillman, Eric; Avery, Michael

    2014-06-01

    Feral swine were targeted for control at Avon Park Air Force Range in south-central Florida to avert damage to sensitive wetland habitats on the 40,000-ha base. We conducted a 5-year study to assess impacts from control to this population that had been recreationally hunted for many years. Control was initiated in early 2009. The feral swine population was monitored from 2008 to 2012 using a passive tracking index (PTI) during the dry and wet seasons and using recreational hunter take rates from the dry season. All three indices showed substantial feral swine declines after implementing control, with indices leveling for the final two study years. Military missions and recreational hunting seasons impacted temporal and spatial consistency of control application, thereby limiting further impacts of control efforts on the feral swine population. The PTI was also able to monitor coyotes, another invasive species on the base, and detect Florida black bear and Florida panther, species of particular concern.

  9. Automatic glaucoma diagnosis through medical imaging informatics.

    PubMed

    Liu, Jiang; Zhang, Zhuo; Wong, Damon Wing Kee; Xu, Yanwu; Yin, Fengshou; Cheng, Jun; Tan, Ngan Meng; Kwoh, Chee Keong; Xu, Dong; Tham, Yih Chung; Aung, Tin; Wong, Tien Yin

    2013-01-01

    Computer-aided diagnosis for screening utilizes computer-based analytical methodologies to process patient information. Glaucoma is the leading irreversible cause of blindness. Due to the lack of an effective and standard screening practice, more than 50% of the cases are undiagnosed, which prevents the early treatment of the disease. To design an automatic glaucoma diagnosis architecture automatic glaucoma diagnosis through medical imaging informatics (AGLAIA-MII) that combines patient personal data, medical retinal fundus image, and patient's genome information for screening. 2258 cases from a population study were used to evaluate the screening software. These cases were attributed with patient personal data, retinal images and quality controlled genome data. Utilizing the multiple kernel learning-based classifier, AGLAIA-MII, combined patient personal data, major image features, and important genome single nucleotide polymorphism (SNP) features. Receiver operating characteristic curves were plotted to compare AGLAIA-MII's performance with classifiers using patient personal data, images, and genome SNP separately. AGLAIA-MII was able to achieve an area under curve value of 0.866, better than 0.551, 0.722 and 0.810 by the individual personal data, image and genome information components, respectively. AGLAIA-MII also demonstrated a substantial improvement over the current glaucoma screening approach based on intraocular pressure. AGLAIA-MII demonstrates for the first time the capability of integrating patients' personal data, medical retinal image and genome information for automatic glaucoma diagnosis and screening in a large dataset from a population study. It paves the way for a holistic approach for automatic objective glaucoma diagnosis and screening.

  10. Polymorphism of SMAD7 gene (rs2337104) and risk of colorectal cancer in an Iranian population: a case-control study

    PubMed Central

    Akbari, Zahra; Safari-Alighiarloo, Nahid; Taleghani, Mohammad Yaghoob; Mirfakhar, Farzaneh Sadat; Asadzadeh Aghdaei, Hamid; Vahedi, Mohsen; Irani Shemirani, Atena; Nazemalhosseini-Mojarad, Ehsan; Zali, Mohammad Reza

    2014-01-01

    Aim: The purpose of this study was to evaluate the influence of intronic polymorphism of the SMAD7 (Mothers Against Decantaplegic Homolog 7) gene (rs2337104) on the risk of colorectal cancer (CRC) and clinicopathological features in an Iranian population. Background: SMAD7 has been identified as an antagonist of transforming growth factor beta (TGF-b)-mediating fibrosis, carcinogenesis, and inflammation. Regarding to the recent genome-wide scan, a risk locus for colorectal cancer at 18q21 has been found, which maps to the SMAD7 gene. Patients and methods: This case-control study was performed on 109 CRC patients and 109 healthy controls recruited in Taleghani Hospital. The genotyping of all samples were done by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from peripheral blood. The association of this polymorphism with the risk of CRC and clinicopathological features was investigated. Results: Our results indicated that there were no significant association between genotypic and allelic frequencies of SMAD7 polymorphism (rs2337104) and CRC risk in our population. Although the T allele is the most frequent one in this population and its frequency was 86.7% in patients compared with 91.7% in controls (OR=1.705, 95% CI= 0.916–3.172). Also, the SMAD7 genotypes were not associated with any clinicopathological characteristics in CRC patients (P>0.05). Conclusion: For the first time, this study results revealed that this SMAD7 polymorphism couldn’t be a potential risk factor for CRC or a prognostic biomarker for prediction of clinicopathological features in an Iranian population. A large-scale case-control study is needed to validate our results. PMID:25289133

  11. Risk for attempted suicide in children and youths after contact with somatic hospitals: a Danish register based nested case-control study.

    PubMed

    Christiansen, E; Stenager, E

    2012-03-01

    A range of studies have found an association between some somatic diseases and increased risk of suicide and attempted suicide. These studies are mostly analyses of adult populations and illnesses related to adulthood. To study the risk of attempted suicide in children and youths with a somatic diagnosis, and to assess a possible association from a somatic perspective. From a cohort of 403 431 individuals (born 1983-89), 3465 children and youths who had attempted suicide were identified. Each case was matched with 20 population controls. 72 765 children and youths constituted the case-control population. All data were obtained from national population registers and analysed in a nested case-control design. Contact of children and youths with a somatic hospital is correlated with increased risk of attempted suicide; the risk peaks in the time immediately after contact. Risk factors were treatment for injury caused by violence, epilepsy, asthma and malformation for males; and spontaneous and medical abortions, treatment for injury caused by violence, epilepsy, asthma, insulin dependent diabetes mellitus and malformation for females. Not all the mentioned diagnoses were significant in the adjusted model. Based on the results of the study a strategy to minimise the risk of attempted suicide among children and youths must be implemented. The strategy should mainly focus on children at high risk-that is, children from families with low socioeconomic status, and children with a psychiatric history, a history of previous suicide attempts and with an unstable somatic disease subsequently causing many admissions.

  12. Occupational exposures and non-Hodgkin's lymphoma: Canadian case-control study.

    PubMed

    Karunanayake, Chandima P; McDuffie, Helen H; Dosman, James A; Spinelli, John J; Pahwa, Punam

    2008-08-07

    The objective was to study the association between Non-Hodgkin's Lymphoma (NHL) and occupational exposures related to long held occupations among males in six provinces of Canada. A population based case-control study was conducted from 1991 to 1994. Males with newly diagnosed NHL (ICD-10) were stratified by province of residence and age group. A total of 513 incident cases and 1506 population based controls were included in the analysis. Conditional logistic regression was conducted to fit statistical models. Based on conditional logistic regression modeling, the following factors independently increased the risk of NHL: farmer and machinist as long held occupations; constant exposure to diesel exhaust fumes; constant exposure to ionizing radiation (radium); and personal history of another cancer. Men who had worked for 20 years or more as farmer and machinist were the most likely to develop NHL. An increased risk of developing NHL is associated with the following: long held occupations of faer and machinist; exposure to diesel fumes; and exposure to ionizing radiation (radium). The risk of NHL increased with the duration of employment as a farmer or machinist.

  13. Fumonisin B1 and Risk of Hepatocellular Carcinoma in Two Chinese Cohorts

    PubMed Central

    Persson, E. Christina; Sewram, Vikash; Evans, Alison A.; London, W. Thomas; Volkwyn, Yvette; Shen, Yen-Ju; Van Zyl, Jacobus A.; Chen, Gang; Lin, Wenyao; Shephard, Gordon S.; Taylor, Philip R.; Fan, Jin-Hu; Dawsey, Sanford M.; Qiao, You-Lin; McGlynn, Katherine A.; Abnet, Christian C.

    2011-01-01

    Fumonisin B1 (FB1), a mycotoxin that contaminates corn in certain climates, has been demonstrated to cause hepatocellular cancer (HCC) in animal models. Whether a relationship between FB1 and HCC exists in humans is not known. To examine the hypothesis, we conducted case-control studies nested within two large cohorts in China; the Haimen City Cohort and the General Population Study of the Nutritional Intervention Trials cohort in Linxian. In the Haimen City Cohort, nail FB1 levels were determined in 271 HCC cases and 280 controls. In the General Population Nutritional Intervention Trial, nail FB1 levels were determined in 72 HCC cases and 147 controls. In each population, odds ratios and 95% confidence intervals (95%CI) from logistic regression models estimated the association between measurable FB1 and HCC, adjusting for hepatitis B virus infection and other factors. A meta-analysis that included both populations was also conducted. The analysis revealed no statistically significant association between FB1 and HCC in either Haimen City (OR=1.10, 95%CI=0.64–1.89) or in Linxian (OR=1.47, 95%CI=0.70–3.07). Similarly, the pooled meta-analysis showed no statistically significant association between FB1 exposure and HCC (OR=1.22, 95%CI=0.79–1.89). These findings, although somewhat preliminary, do not support an associated between FB1 and HCC. PMID:22142693

  14. Risk factors for breast cancer by oestrogen receptor status: a population-based case-control study.

    PubMed Central

    Cooper, J. A.; Rohan, T. E.; Cant, E. L.; Horsfall, D. J.; Tilley, W. D.

    1989-01-01

    Data from a population-based case-control study conducted in Adelaide, South Australia, and involving 451 case-control pairs, were analysed to determine whether the associations of menstrual, reproductive, dietary and other factors with risk of breast cancer differed by oestrogen receptor (ER) status. Data on ER status were available for 380 cases. The proportion of tumours which were ER+ increased with age, and there was a higher proportion of ER+ tumours in post-menopausal than in premenopausal women. Both oral contraceptive use (P = 0.055) and cigarette smoking (P = 0.047) were associated with increased (unadjusted) risk of ER- cancer, while having little association with risk of ER+ cancer. Most dietary factors had little association with risk of either cancer type, the main exception being the reduction in risk of ER- breast cancer with increasing beta-carotene intake (P for trend = 0.017). In general, however, links with the factors examined were not strong enough to suggest different causal pathways for ER- and ER+ breast cancer. PMID:2757918

  15. Melanocytic nevi, nevus genes and melanoma risk in a large case-control study in the United Kingdom

    PubMed Central

    Newton-Bishop, Julia A; Chang, Yu-Mei; Iles, Mark M; Taylor, John C; Bakker, Bert; Chan, May; Leake, Susan; Karpavicius, Birute; Haynes, Sue; Fitzgibbon, Elaine; Elliott, Faye; Kanetsky, Peter A.; Harland, Mark; Barrett, Jennifer H; Bishop, D Timothy

    2010-01-01

    Background Increased number of melanocytic nevi is a potent melanoma risk factor. We have carried out a large population-based case-control study to explore the environmental and genetic determinants of nevi and the relationship with melanoma risk. Methods We report nevus phenotype in relation to differing patterns of sun exposure, inherited variation at loci shown in recent genome-wide association studies to be nevus genes, and risk. Results Increased numbers of nevi were associated with holiday sun exposure, particularly on intermittently sun-exposed body sites (test for trend p<0.0001). Large nevi were also associated with holiday sun exposure (p=0.002). Single nucleotide polymorphisms (SNPs) on chromosomes 9 and 22 were associated with increased numbers of nevi (p=0.04 and p=0.002 respectively) and larger nevi (p=0.03 and p=0.002), whereas that on chromosome 6 was associated only with large nevi (p=0.01). Melanoma risk was associated with increased nevus count, large nevi and atypical nevi for tumors in all body sites (including rare sites) irrespective of age. The risk persisted when adjusted for inheritance of nevus SNPs. Conclusions The at-risk nevus phenotype is associated with behaviors known to increase melanoma risk (holiday sun exposure). Although SNPs on chromosomes 6, 9 and 22 were shown to be nevus genes they explained only a small proportion of melanoma risk and nevus phenotype; therefore a number of nevus genes likely remain to be identified. Impact This paper confirms the importance of nevi in melanoma pathogenesis and increases understanding of their genetic determinants. PMID:20647408

  16. Association of bladder pain syndrome/interstitial cystitis with urinary calculus: a nationwide population-based study.

    PubMed

    Keller, Joseph; Chen, Yi-Kuang; Lin, Herng-Ching

    2013-04-01

    Although one prior study reported an association between bladder pain syndrome/interstitial cystitis (BPS/IC) and urinary calculi (UC), no population-based study to date has been conducted to explore this relationship. Therefore, using a population-based data set in Taiwan, this study set out to investigate the association between BPS/IC and a prior diagnosis of UC. This study included 9,269 cases who had received their first-time diagnosis of BPS/IC between 2006 and 2007 and 46,345 randomly selected controls. We used conditional logistic regression analysis to compute the odds ratio (OR) and its corresponding 95 % confidence interval (CI) for having been previously diagnosed with UC between cases and controls. There was a significant difference in the prevalence of prior UC between cases and controls (8.1 vs 4.3 %, p < 0.001). Conditional logistic regression analysis revealed that cases were more likely to have been previously diagnosed with UC than controls (OR = 1.70; 95 % CI = 1.56-1.84) after adjusting for chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraine, sicca syndrome, allergy, endometriosis, and asthma. BPS/IC was found to be significantly associated with prior UC regardless of stone location; the adjusted ORs of kidney calculus, ureter calculus, bladder calculus, and unspecified calculus when compared to controls were 1.58 (95 % CI = 1.38-1.81), 1.73 (95 % CI = 1.45-2.05), 3.80 (95 % CI = 2.18-6.62), and 1.83 (95 % CI = 1.59-2.11), respectively. This work generates the hypothesis that UC may be associated with BPS/IC.

  17. Driving following Kava Use and Road Traffic Injuries: A Population-Based Case-Control Study in Fiji (TRIP 14).

    PubMed

    Wainiqolo, Iris; Kafoa, Berlin; Kool, Bridget; Robinson, Elizabeth; Herman, Josephine; McCaig, Eddie; Ameratunga, Shanthi

    2016-01-01

    To investigate the association between kava use and the risk of four-wheeled motor vehicle crashes in Fiji. Kava is a traditional beverage commonly consumed in many Pacific Island Countries. Herbal anxiolytics containing smaller doses of kava are more widely available. Data for this population-based case-control study were collected from drivers of 'case' vehicles involved in serious injury-involved crashes (where at least one road user was killed or admitted to hospital for 12 hours or more) and 'control' vehicles representative of 'driving time' in the study base. Structured interviewer administered questionnaires collected self-reported participant data on demographic characteristics and a range of risk factors including kava use and potential confounders. Unconditional logistic regression models estimated odds ratios relating to the association between kava use and injury-involved crash risk. Overall, 23% and 4% of drivers of case and control vehicles, respectively, reported consuming kava in the 12 hours prior to the crash or road survey. After controlling for assessed confounders, driving following kava use was associated with a four-fold increase in the odds of crash involvement (Odds ratio: 4.70; 95% CI: 1.90-11.63). The related population attributable risk was 18.37% (95% CI: 13.77-22.72). Acknowledging limited statistical power, we did not find a significant interaction in this association with concurrent alcohol use. In this study conducted in a setting where recreational kava consumption is common, driving following the use of kava was associated with a significant excess of serious-injury involved road crashes. The precautionary principle would suggest road safety strategies should explicitly recommend avoiding driving following kava use, particularly in communities where recreational use is common.

  18. Burden of group A streptococcal meningitis in Salvador, Brazil: report of 11 years of population-based surveillance

    PubMed Central

    Santos, Milena Soares; de Sousa Ribeiro, Guilherme; Oliveira, Tainara Queiroz; Santos, Renan Cardoso Nery; Gouveia, Edilane; Salgado, Kátia; Takahashi, Daniele; Fontes, Cleuber; Campos, Leila Carvalho; Reis, Mitermayer Galvão; Ko, Albert Icksang; Reis, Joice Neves

    2009-01-01

    1.2 Summary Background Over recent decades, a resurgence of invasive group A streptococcal (GAS) infections has been observed; GAS remains a rare cause of pyogenic meningitis. We report herein population-based findings of long-term surveillance for GAS meningitis in Salvador, Brazil, and estimate the overall burden of invasive GAS infections. Methods From February 1996 to January 2006 we conducted active surveillance for GAS meningitis in the state reference hospital for infectious diseases in Salvador, Brazil. Data on clinical presentation, laboratory records, and outcome were collected through interviews and chart review. GAS isolates were evaluated for antimicrobial susceptibility and emm type. Results We identified 20 cases of GAS meningitis, which accounted for 0.9% of all culture-proven bacterial meningitis in the study period. The mean annual incidence of GAS meningitis was 0.03 cases per 100 000 population in metropolitan Salvador and peaked in children <1 year of age (0.67 cases per 100 000 population). Among 17 cases with clinical information available, 41% required intensive care unit support and 25% died. Tested isolates were susceptible to penicillin and exhibited large emm type diversity. Based on the incidence of GAS meningitis, we estimate that the annual incidence of GAS infection is 3 cases per 100 000 population in metropolitan Salvador. Conclusions Although rare, GAS is a life-threatening cause of bacterial meningitis. Knowledge of the incidence and emm type variability of the disease is necessary for planning immunization strategies. PMID:19019714

  19. Simple Genetic Distance-Optimized Field Deployments for Clonal Seed Orchards Based on Microsatellite Markers: As a Case of Chinese Pine Seed Orchard.

    PubMed

    Yuan, Huwei; Niu, Shihui; El-Kassaby, Yousry A; Li, Yue; Li, Wei

    2016-01-01

    Chinese pine seed orchards are in a period of transition from first-generation to advanced-generations. How to effectively select populations for second-generation seed orchards and significantly increase genetic gain through rational deployment have become major issues. In this study, we examined open- and control-pollinated progeny of the first-generation Chinese pine seed orchards in Zhengning (Gansu Province, China) and Xixian (Shanxi Province, China) to address issues related to phenotypic selection for high volume growth, genetic diversity analysis and genetic distance-based phylogenetic analysis of the selections by simple sequence repeats (SSRs), and phylogenetic relationship-based field deployment for advanced-generation orchards. In total, 40, 28, 20, and 13 superior individuals were selected from the large-scale no-pedigree open-pollinated progeny of Zhengning (ZN-NP), open-pollinated families of Zhengning (ZN-OP), open-pollinated families of Xixian (XX-OP), and control-pollinated families of Xixian, with mean volume dominance ratios of 0.83, 0.15, 0.25, and 0.20, respectively. Phylogenetic relationship analysis of the ZN-NP and XX-OP populations showed that the 40 superior individuals in the ZN-NP selected population belonged to 23 families and could be further divided into five phylogenetic groups, and that families in the same group were closely related. Similarly, 20 families in the XX-OP population were related to varying degrees. Based on these results, we found that second-generation Chinese pine seed orchards in Zhengning and Xixian should adopt a grouped, unbalanced, complete, fixed block design and an unbalanced, incomplete, fixed block design, respectively. This study will provide practical references for applying molecular markers to establishing advanced-generation seed orchards.

  20. Of Pesticides and Men: A California Story of Genes and Environment in Parkinson’s Disease

    PubMed Central

    Ritz, BR; Paul, KC; Bronstein, JM

    2018-01-01

    At the start of the post-genomics era, most Parkinson’s disease (PD) etiology cannot be explained by our knowledge of genetic or environmental factors alone. For more than a decade, we have explored gene-environment (GxE) interactions possibly responsible for the heterogeneity of genetic as well as environmental results across populations. We developed three pesticide exposure measures (ambient due to agricultural applications, home and garden use, occupational use) in a large population-based case-control study of incident PD in central California. Specifically, we assessed interactions with genes responsible for pesticide metabolism (PON1); transport across the blood brain barrier (ABCB1); pesticides interfering with or depending on dopamine transporter activity (DAT) and dopamine metabolism (ALDH2); impacting mitochondrial function via oxidative/nitrosative stress (NOS1) or proteasome inhibition (SKP1); and contributing to immune dysregulation (HLA-DR). These studies established some specificity for pesticides’ neurodegenerative actions, contributed biologic plausibility to epidemiologic findings, and identified genetically susceptible populations. PMID:26857251

  1. Optimal exploitation strategies for an animal population in a Markovian environment: A theory and an example

    USGS Publications Warehouse

    Anderson, D.R.

    1975-01-01

    Optimal exploitation strategies were studied for an animal population in a Markovian (stochastic, serially correlated) environment. This is a general case and encompasses a number of important special cases as simplifications. Extensive empirical data on the Mallard (Anas platyrhynchos) were used as an example of general theory. The number of small ponds on the central breeding grounds was used as an index to the state of the environment. A general mathematical model was formulated to provide a synthesis of the existing literature, estimates of parameters developed from an analysis of data, and hypotheses regarding the specific effect of exploitation on total survival. The literature and analysis of data were inconclusive concerning the effect of exploitation on survival. Therefore, two hypotheses were explored: (1) exploitation mortality represents a largely additive form of mortality, and (2) exploitation mortality is compensatory with other forms of mortality, at least to some threshold level. Models incorporating these two hypotheses were formulated as stochastic dynamic programming models and optimal exploitation strategies were derived numerically on a digital computer. Optimal exploitation strategies were found to exist under the rather general conditions. Direct feedback control was an integral component in the optimal decision-making process. Optimal exploitation was found to be substantially different depending upon the hypothesis regarding the effect of exploitation on the population. If we assume that exploitation is largely an additive force of mortality in Mallards, then optimal exploitation decisions are a convex function of the size of the breeding population and a linear or slight concave function of the environmental conditions. Under the hypothesis of compensatory mortality forces, optimal exploitation decisions are approximately linearly related to the size of the Mallard breeding population. Dynamic programming is suggested as a very general formulation for realistic solutions to the general optimal exploitation problem. The concepts of state vectors and stage transformations are completely general. Populations can be modeled stochastically and the objective function can include extra-biological factors. The optimal level of exploitation in year t must be based on the observed size of the population and the state of the environment in year t unless the dynamics of the population, the state of the environment, and the result of the exploitation decisions are completely deterministic. Exploitation based on an average harvest, or harvest rate, or designed to maintain a constant breeding population size is inefficient.

  2. Target prioritization and strategy selection for active case-finding of pulmonary tuberculosis: a tool to support country-level project planning.

    PubMed

    Nishikiori, Nobuyuki; Van Weezenbeek, Catharina

    2013-02-02

    Despite the progress made in the past decade, tuberculosis (TB) control still faces significant challenges. In many countries with declining TB incidence, the disease tends to concentrate in vulnerable populations that often have limited access to health care. In light of the limitations of the current case-finding approach and the global urgency to improve case detection, active case-finding (ACF) has been suggested as an important complementary strategy to accelerate tuberculosis control especially among high-risk populations. The present exercise aims to develop a model that can be used for county-level project planning. A simple deterministic model was developed to calculate the number of estimated TB cases diagnosed and the associated costs of diagnosis. The model was designed to compare cost-effectiveness parameters, such as the cost per case detected, for different diagnostic algorithms when they are applied to different risk populations. The model was transformed into a web-based tool that can support national TB programmes and civil society partners in designing ACF activities. According to the model output, tuberculosis active case-finding can be a costly endeavor, depending on the target population and the diagnostic strategy. The analysis suggests the following: (1) Active case-finding activities are cost-effective only if the tuberculosis prevalence among the target population is high. (2) Extensive diagnostic methods (e.g. X-ray screening for the entire group, use of sputum culture or molecular diagnostics) can be applied only to very high-risk groups such as TB contacts, prisoners or people living with human immunodeficiency virus (HIV) infection. (3) Basic diagnostic approaches such as TB symptom screening are always applicable although the diagnostic yield is very limited. The cost-effectiveness parameter was sensitive to local diagnostic costs and the tuberculosis prevalence of target populations. The prioritization of appropriate target populations and careful selection of cost-effective diagnostic strategies are critical prerequisites for rational active case-finding activities. A decision to conduct such activities should be based on the setting-specific cost-effectiveness analysis and programmatic assessment. A web-based tool was developed and is available to support national tuberculosis programmes and partners in the formulation of cost-effective active case-finding activities at the national and subnational levels.

  3. Statins are Associated With a Reduced Risk of Brain Cancer: A Population-Based Case-Control Study.

    PubMed

    Chen, Brian K; Chiu, Hui-Fen; Yang, Chun-Yuh

    2016-04-01

    The aim of this study was to investigate whether statin utilization is associated with brain cancer risk.A population-based case-control study was conducted using nationally representative claims data from the National Health Insurance Bureau in Taiwan. Cases included all patients 50 years and older who received an index diagnosis of brain cancer between 2004 and 2011. Our controls were matched by age, sex, and index date. We estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) using multiple logistic regression.We examined 213 brain cancer cases and 852 controls. The unadjusted ORs for any statin prescription was 0.77 (95% CI = 0.50-1.18) and the adjusted OR was 0.59 (95% CI = 0.37-0.96). Compared with no use of statins, the adjusted ORs were 0.68 (95% CI = 0.38-1.24) for the group having been prescribed with statins with cumulative defined daily dose (DDD) below 144.67 DDDs and 0.50 (95% CI = 0.28-0.97) for the group with the cumulative statin use of 144.67 DDDs or more.The results of this study suggest that statins may reduce the risk of brain cancer.

  4. Communicable disease surveillance and control in the context of conflict and mass displacement in Syria.

    PubMed

    Ismail, Sharif A; Abbara, Aula; Collin, Simon M; Orcutt, Miriam; Coutts, Adam P; Maziak, Wasim; Sahloul, Zaher; Dar, Osman; Corrah, Tumena; Fouad, Fouad M

    2016-06-01

    To describe trends in major communicable diseases in Syria during the ongoing conflict, and the challenges to communicable disease surveillance and control in the context of dynamic, large-scale population displacement, unplanned mass gatherings, and disruption to critical infrastructure. A rapid review of the peer-reviewed and non-peer-reviewed literature from 2005 to 2015 was performed, augmented by secondary analysis of monitoring data from two disease early warning systems currently operational in Syria, focusing mainly on three diseases: tuberculosis (TB), measles, and polio. Trend data show discrepancies in case report numbers between government and non-government controlled areas, especially for TB, but interpretation is hampered by uncertainties over sentinel surveillance coverage and base population numbers. Communicable disease control has been undermined by a combination of governance fragmentation, direct and indirect damage to facilities and systems, and health worker flight. Five years into the crisis, some progress has been made in disease surveillance, but governance and coordination problems, variable immunization coverage, and the dynamic and indiscriminate nature of the conflict continue to pose a serious threat to population health in Syria and surrounding countries. The risk of major cross-border communicable disease outbreaks is high, and challenges for health in a post-conflict Syria are formidable. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  5. The Clinical Next-Generation Sequencing Database: A Tool for the Unified Management of Clinical Information and Genetic Variants to Accelerate Variant Pathogenicity Classification.

    PubMed

    Nishio, Shin-Ya; Usami, Shin-Ichi

    2017-03-01

    Recent advances in next-generation sequencing (NGS) have given rise to new challenges due to the difficulties in variant pathogenicity interpretation and large dataset management, including many kinds of public population databases as well as public or commercial disease-specific databases. Here, we report a new database development tool, named the "Clinical NGS Database," for improving clinical NGS workflow through the unified management of variant information and clinical information. This database software offers a two-feature approach to variant pathogenicity classification. The first of these approaches is a phenotype similarity-based approach. This database allows the easy comparison of the detailed phenotype of each patient with the average phenotype of the same gene mutation at the variant or gene level. It is also possible to browse patients with the same gene mutation quickly. The other approach is a statistical approach to variant pathogenicity classification based on the use of the odds ratio for comparisons between the case and the control for each inheritance mode (families with apparently autosomal dominant inheritance vs. control, and families with apparently autosomal recessive inheritance vs. control). A number of case studies are also presented to illustrate the utility of this database. © 2016 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

  6. Lot quality assurance sampling (LQAS) for monitoring a leprosy elimination program.

    PubMed

    Gupte, M D; Narasimhamurthy, B

    1999-06-01

    In a statistical sense, prevalences of leprosy in different geographical areas can be called very low or rare. Conventional survey methods to monitor leprosy control programs, therefore, need large sample sizes, are expensive, and are time-consuming. Further, with the lowering of prevalence to the near-desired target level, 1 case per 10,000 population at national or subnational levels, the program administrator's concern will be shifted to smaller areas, e.g., districts, for assessment and, if needed, for necessary interventions. In this paper, Lot Quality Assurance Sampling (LQAS), a quality control tool in industry, is proposed to identify districts/regions having a prevalence of leprosy at or above a certain target level, e.g., 1 in 10,000. This technique can also be considered for identifying districts/regions at or below the target level of 1 per 10,000, i.e., areas where the elimination level is attained. For simulating various situations and strategies, a hypothetical computerized population of 10 million persons was created. This population mimics the actual population in terms of the empirical information on rural/urban distributions and the distribution of households by size for the state of Tamil Nadu, India. Various levels with respect to leprosy prevalence are created using this population. The distribution of the number of cases in the population was expected to follow the Poisson process, and this was also confirmed by examination. Sample sizes and corresponding critical values were computed using Poisson approximation. Initially, villages/towns are selected from the population and from each selected village/town households are selected using systematic sampling. Households instead of individuals are used as sampling units. This sampling procedure was simulated 1000 times in the computer from the base population. The results in four different prevalence situations meet the required limits of Type I error of 5% and 90% Power. It is concluded that after validation under field conditions, this method can be considered for a rapid assessment of the leprosy situation.

  7. Childhood ADHD Is Strongly Associated with a Broad Range of Psychiatric Disorders during Adolescence: A Population-Based Birth Cohort Study

    ERIC Educational Resources Information Center

    Yoshimasu, Kouichi; Barbaresi, William J.; Colligan, Robert C.; Voigt, Robert G.; Killian, Jill M.; Weaver, Amy L.; Katusic, Slavica K.

    2012-01-01

    Background: To evaluate associations between attention-deficit/hyperactivity disorder (ADHD) and comorbid psychiatric disorders using research-identified incident cases of ADHD and population-based controls. Methods: Subjects included a birth cohort of all children born 1976-1982 remaining in Rochester, MN after age five (n = 5,718). Among them we…

  8. Ecological feedbacks can reduce population-level efficacy of wildlife fertility control

    USGS Publications Warehouse

    Ransom, Jason I.; Powers, Jenny G.; Hobbs, N. Thompson; Baker, Dan L.

    2014-01-01

    1. Anthropogenic stress on natural systems, particularly the fragmentation of landscapes and the extirpation of predators from food webs, has intensified the need to regulate abundance of wildlife populations with management. Controlling population growth using fertility control has been considered for almost four decades, but nearly all research has focused on understanding effects of fertility control agents on individual animals. Questions about the efficacy of fertility control as a way to control populations remain largely unanswered. 2. Collateral consequences of contraception can produce unexpected changes in birth rates, survival, immigration and emigration that may reduce the effectiveness of regulating animal abundance. The magnitude and frequency of such effects vary with species-specific social and reproductive systems, as well as connectivity of populations. Developing models that incorporate static demographic parameters from populations not controlled by contraception may bias predictions of fertility control efficacy. 3. Many population-level studies demonstrate that changes in survival and immigration induced by fertility control can compensate for the reduction in births caused by contraception. The most successful cases of regulating populations using fertility control come from applications of contraceptives to small, closed populations of gregarious and easily accessed species. 4. Fertility control can result in artificial selection pressures on the population and may lead to long-term unintentional genetic consequences. The magnitude of such selection is dependent on individual heritability and behavioural traits, as well as environmental variation. 5. Synthesis and applications. Understanding species' life-history strategies, biology, behavioural ecology and ecological context is critical to developing realistic expectations of regulating populations using fertility control. Before time, effort and funding are invested in wildlife contraception, managers may need to consider the possibility that many species and populations can compensate for reduction in fecundity, and this could minimize any reduction in population growth rate.

  9. Ecological feedbacks can reduce population-level efficacy of wildlife fertility control

    PubMed Central

    Ransom, Jason I; Powers, Jenny G; Thompson Hobbs, N; Baker, Dan L

    2014-01-01

    Anthropogenic stress on natural systems, particularly the fragmentation of landscapes and the extirpation of predators from food webs, has intensified the need to regulate abundance of wildlife populations with management. Controlling population growth using fertility control has been considered for almost four decades, but nearly all research has focused on understanding effects of fertility control agents on individual animals. Questions about the efficacy of fertility control as a way to control populations remain largely unanswered. Collateral consequences of contraception can produce unexpected changes in birth rates, survival, immigration and emigration that may reduce the effectiveness of regulating animal abundance. The magnitude and frequency of such effects vary with species-specific social and reproductive systems, as well as connectivity of populations. Developing models that incorporate static demographic parameters from populations not controlled by contraception may bias predictions of fertility control efficacy. Many population-level studies demonstrate that changes in survival and immigration induced by fertility control can compensate for the reduction in births caused by contraception. The most successful cases of regulating populations using fertility control come from applications of contraceptives to small, closed populations of gregarious and easily accessed species. Fertility control can result in artificial selection pressures on the population and may lead to long-term unintentional genetic consequences. The magnitude of such selection is dependent on individual heritability and behavioural traits, as well as environmental variation. Synthesis and applications. Understanding species' life-history strategies, biology, behavioural ecology and ecological context is critical to developing realistic expectations of regulating populations using fertility control. Before time, effort and funding are invested in wildlife contraception, managers may need to consider the possibility that many species and populations can compensate for reduction in fecundity, and this could minimize any reduction in population growth rate. PMID:25558083

  10. Effect of using an audience response system on learning environment, motivation and long-term retention, during case-discussions in a large group of undergraduate veterinary clinical pharmacology students.

    PubMed

    Doucet, Michèle; Vrins, André; Harvey, Denis

    2009-12-01

    Teaching methods that provide an opportunity for individual engagement and focussed feedback are required to create an active learning environment for case-based teaching in large groups. A prospective observational controlled study was conducted to evaluate whether the use of an audience response system (ARS) would promote an active learning environment during case-based discussions in large groups, have an impact on student motivation and improve long-term retention. Group A (N = 83) participated in large group case discussions where student participation was voluntary, while for group B (N = 86) an ARS was used. Data collection methods included student and teacher surveys, student focus group interviews, independent observations and 1-year post-course testing. Results indicated that the use of an ARS provided an active learning environment during case-based discussions in large groups by favouring engagement, observation and critical reflection and by increasing student and teacher motivation. Although final exam results were significantly improved in group B, long-term retention was not significantly different between groups. It was concluded that ARS use significantly improved the learning experience associated with case-based discussions in a large group of undergraduate students.

  11. Population-based family case-control proband study on familial aggregation of metabolic syndrome: finding from Taiwanese people involved in Keelung community-based integrated screening (KCIS no. 5).

    PubMed

    Chiu, Yueh-Hsia; Lin, Wen-Yuan; Wang, Po-En; Chen, Yao-Der; Wang, Ting-Ting; Warwick, Jane; Chen, Tony Hsiu-Hsi

    2007-03-01

    A population-based case-control proband study was undertaken to elucidate familial aggregation, independent environmental factors, and the interaction between them. A total of 7308 metabolic syndrome (MET-S) cases were identified from the Keelung community-based integrated screening programme between 1999 and 2002. The study has a case-control/family sampling design. A total of 1417 case probands were randomly selected from 3225 metabolic syndrome cases and the corresponding 2458 controls selected from 16,519 subjects without metabolic syndrome by matching on sex, age (+/-3 years) and place of residence. The generalized estimation equation model was used to estimate odds ratios and corresponding 95% confidence intervals. The risk for having metabolic syndrome among family members for cases versus control probands was 1.56-fold (1.29-1.89) after controlling for significant environmental factors. Higher risk of metabolic syndrome was found in parents than spouse. Low education against high education had 2.06-fold (1.36-3.13) risk for metabolic syndrome. Betel quid chewing was positively associated with the risk of MET-S, with 1.99-fold (1.13-3.53) risk for 1-9 pieces and 1.76-fold (0.96-3.23) risk for >or=10 pieces compared with non-chewer. Moderate and high intensity of non-occupational exercise led to 21.0% (OR=0.79 (0.63-0.98)) and 26.0% (OR=0.74 (0.59-0.94)) reduction in the risk for metabolic syndrome, respectively. The frequent consumption of vegetable reduced 24.0% (OR=0.76 (0.62-0.92)) risk for MET-S. The frequent consumption of coffee was associated the increased risk for metabolic syndrome (OR=1.32 (1.07-1.64)). The present study confirmed the risk of metabolic syndrome not only has the tendency towards familial aggregation but is affected by independent effect of environmental or individual correlates.

  12. Impact of floating population on the epidemic of tuberculosis: a spatial analysis

    NASA Astrophysics Data System (ADS)

    Jia, Zhongwei; He, Xiaoxin; Zhao, Wenjuan; An, Yansheng; Cao, Wuchun; Li, Xiaowen

    2007-06-01

    According to the report issued by the Health Bureau of Beijing that the number of newly registered active pulmonary tuberculosis cases in floating population exceeded half of that in registered permanent residence in 2006. More attention has been paid to the tuberculosis of floating population. Materials and methods: The population data included in the studied was reported by the Beijing Police Bureau in 2004, and the case source from 2004 to 2006 was provided by Beijing Research Institute for TB Control. Two GIS-based methods have been used to detect the hot spots of tuberculosis in 18 districts of Beijing. Results: The distributions of hot spots of tuberculosis in Beijing are significantly associated with that of floating people. Most likely cluster from all population matches with those from floating population, which is stable from 2004 to 2006. Conclusion: The spatial analytical results indicated that the floating population has a drastic influence on the epidemic of tuberculosis in Beijing. The tuberculosis control measures should incorporate the effect of floating population.

  13. Diarrheagenic Escherichia coli and Acute Gastroenteritis in Children in Davidson County, Tennessee, United States: A Case-control Study.

    PubMed

    Imdad, Aamer; Foster, Monique A; Iqbal, Junaid; Fonnesbeck, Christopher; Payne, Daniel C; Zhang, Chengxian; Chappell, James D; Halasa, Natasha; Gómez-Duarte, Oscar G

    2018-06-01

    Diarrheagenic Escherichia coli (DEC) is an important cause of acute gastroenteritis in children; however, there is limited information available on the epidemiology, phylogenetics, serotyping and antibiotic susceptibility of DEC in children in the United States. The aim of this study was to determine the molecular epidemiology of DEC among children with and without acute gastroenteritis in Davidson County, Tennessee. This prospective, frequency matched, case-control study recruited subjects 15 days to 17 years of age and detected DEC with polymerase chain reaction from stool samples. Additional testing was done to define phylogenetics and antibiotics resistance. Among 1267 participants, 857 cases and 410 controls, 5.5% were positive for at least one subtype of DEC. Enteroaggregative E. coli [n = 32 (45%)] was the most common subtype followed by enteropathogenic E. coli (EPEC) [n = 30 (43%)], Shiga toxin-producing E. coli [n = 4 (6%)] and diffusely adherent E. coli [n = 4 (6%)]. No significant difference in prevalence of DEC was found between cases (5%) and controls (7%) [odds ratio: 0.66 (95% confidence interval: 0.4-1.07)], and results were similar when data were stratified by subtypes and adjusted for age, sex, race and ethnicity. Substantial diversity was found among DEC isolates in terms of phylotypes and serotypes, and a large proportion was resistant to, at least, one antibiotic. Enteroaggregative E. coli and enteropathogenic E. coli were frequently found in both cases and controls in this study population. DNA-based methods for detection of these subtypes need further investigation to help differentiate between pathogenic and colonizing strains.

  14. Lung Cancer Risk Among Hairdressers: A Pooled Analysis of Case-Control Studies Conducted Between 1985 and 2010

    PubMed Central

    Olsson, Ann C.; Xu, Yiwen; Schüz, Joachim; Vlaanderen, Jelle; Kromhout, Hans; Vermeulen, Roel; Peters, Susan; Stücker, Isabelle; Guida, Florence; Brüske, Irene; Wichmann, Heinz-Erich; Consonni, Dario; Landi, Maria Teresa; Caporaso, Neil; Tse, Lap Ah; Yu, Ignatius Tak-sun; Siemiatycki, Jack; Richardson, Lesley; Mirabelli, Dario; Richiardi, Lorenzo; Simonato, Lorenzo; Gustavsson, Per; Plato, Nils; Jöckel, Karl-Heinz; Ahrens, Wolfgang; Pohlabeln, Hermann; Tardón, Adonina; Zaridze, David; Marcus, Michael W.; ‘t Mannetje, Andrea; Pearce, Neil; McLaughlin, John; Demers, Paul; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Boffetta, Paolo; Fortes, Cristina; Bueno-de-Mesquita, Bas; Kendzia, Benjamin; Behrens, Thomas; Pesch, Beate; Brüning, Thomas; Straif, Kurt

    2013-01-01

    Increased lung cancer risks among hairdressers were observed in large registry-based cohort studies from Scandinavia, but these studies could not adjust for smoking. Our objective was to evaluate the lung cancer risk among hairdressers while adjusting for smoking and other confounders in a pooled database of 16 case-control studies conducted in Europe, Canada, China, and New Zealand between 1985 and 2010 (the Pooled Analysis of Case-Control Studies on the Joint Effects of Occupational Carcinogens in the Development of Lung Cancer). Lifetime occupational and smoking information was collected through interviews with 19,369 cases of lung cancer and 23,674 matched population or hospital controls. Overall, 170 cases and 167 controls had ever worked as hairdresser or barber. The odds ratios for lung cancer in women were 1.65 (95% confidence interval (CI): 1.16, 2.35) without adjustment for smoking and 1.12 (95% CI: 0.75, 1.68) with adjustment for smoking; however, women employed before 1954 also experienced an increased lung cancer risk after adjustment for smoking (odds ratio = 2.66, 95% CI: 1.09, 6.47). The odds ratios in male hairdressers/barbers were generally not elevated, except for an increased odds ratio for adenocarcinoma in long-term barbers (odds ratio = 2.20, 95% CI: 1.02, 4.77). Our results suggest that the increased lung cancer risks among hairdressers are due to their smoking behavior; single elevated risk estimates should be interpreted with caution and need replication in other studies. PMID:24068200

  15. Cadmium exposure and risk of prostate cancer: a meta-analysis of cohort and case-control studies among the general and occupational populations

    PubMed Central

    Chen, Cheng; Xun, Pengcheng; Nishijo, Muneko; Carter, Sue; He, Ka

    2016-01-01

    We aimed to evaluate the association of cadmium exposure with the risk of prostate cancer in both the general and occupational populations. Online database searches were performed for studies of prostate cancer risk and cadmium exposure. Twelve cohort studies (5 in the general, 7 in occupational populations) and 9 case-control studies (3 in the general, 6 in occupational populations) were identified. Five/seven cohort studies in the general and occupational populations consist of 78,263/13, 434 participants with a mean follow-up of 12.1/43.0 years, respectively. Case-control studies include 334 cases/670 controls in the general population, and 1,315 cases/4,477 controls in occupational populations. Comparing the highest to the lowest category of cadmium exposure in the general population, the weighted relative risk of prostate cancer incidence and mortality among cohort studies, and the weighted odds ratio in case-control studies were 1.05 (95%CI [0.91, 1.22]), 0.83 (95%CI [0.35, 1.98]), and 1.27 (95%CI [0.58,2.78]), respectively. For occupational populations, the weighted OR in case-control studies was 1.17 (95%CI [0.85, 1.62]), and the weighted standardized mortality ratio in cohort studies was 98 (95%CI [75, 126]). Accumulated epidemiological evidence does not support the hypothesis that cadmium exposure may increase the risk of prostate cancer in either the general or occupational populations. PMID:27174617

  16. Cadmium exposure and risk of prostate cancer: a meta-analysis of cohort and case-control studies among the general and occupational populations.

    PubMed

    Chen, Cheng; Xun, Pengcheng; Nishijo, Muneko; Carter, Sue; He, Ka

    2016-05-13

    We aimed to evaluate the association of cadmium exposure with the risk of prostate cancer in both the general and occupational populations. Online database searches were performed for studies of prostate cancer risk and cadmium exposure. Twelve cohort studies (5 in the general, 7 in occupational populations) and 9 case-control studies (3 in the general, 6 in occupational populations) were identified. Five/seven cohort studies in the general and occupational populations consist of 78,263/13, 434 participants with a mean follow-up of 12.1/43.0 years, respectively. Case-control studies include 334 cases/670 controls in the general population, and 1,315 cases/4,477 controls in occupational populations. Comparing the highest to the lowest category of cadmium exposure in the general population, the weighted relative risk of prostate cancer incidence and mortality among cohort studies, and the weighted odds ratio in case-control studies were 1.05 (95%CI [0.91, 1.22]), 0.83 (95%CI [0.35, 1.98]), and 1.27 (95%CI [0.58,2.78]), respectively. For occupational populations, the weighted OR in case-control studies was 1.17 (95%CI [0.85, 1.62]), and the weighted standardized mortality ratio in cohort studies was 98 (95%CI [75, 126]). Accumulated epidemiological evidence does not support the hypothesis that cadmium exposure may increase the risk of prostate cancer in either the general or occupational populations.

  17. Optimized PID control of depth of hypnosis in anesthesia.

    PubMed

    Padula, Fabrizio; Ionescu, Clara; Latronico, Nicola; Paltenghi, Massimiliano; Visioli, Antonio; Vivacqua, Giulio

    2017-06-01

    This paper addresses the use of proportional-integral-derivative controllers for regulating the depth of hypnosis in anesthesia by using propofol administration and the bispectral index as a controlled variable. In fact, introducing an automatic control system might provide significant benefits for the patient in reducing the risk for under- and over-dosing. In this study, the controller parameters are obtained through genetic algorithms by solving a min-max optimization problem. A set of 12 patient models representative of a large population variance is used to test controller robustness. The worst-case performance in the considered population is minimized considering two different scenarios: the induction case and the maintenance case. Our results indicate that including a gain scheduling strategy enables optimal performance for induction and maintenance phases, separately. Using a single tuning to address both tasks may results in a loss of performance up to 102% in the induction phase and up to 31% in the maintenance phase. Further on, it is shown that a suitably designed low-pass filter on the controller output can handle the trade-off between the performance and the noise effect in the control variable. Optimally tuned PID controllers provide a fast induction time with an acceptable overshoot and a satisfactory disturbance rejection performance during maintenance. These features make them a very good tool for comparison when other control algorithms are developed. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Evidence for Association of the E23K Variant of KCNJ11 Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis

    PubMed Central

    Lasram, Khaled; Ben Halim, Nizar; Hsouna, Sana; Kefi, Rym; Arfa, Imen; Ghazouani, Welid; Jamoussi, Henda; Benrahma, Houda; Kharrat, Najla; Rebai, Ahmed; Ben Ammar, Slim; Bahri, Sonia; Barakat, Abdelhamid; Abid, Abdelmajid; Abdelhak, Sonia

    2014-01-01

    Aims. Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.). Results. A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95% CI = 1.14–2.27, and P = 0.007). Furthermore, our meta-analysis has confirmed the significant role of the E23K variant in susceptibility of Type 2 diabetes in Tunisian and Arab populations (OR = 1.29, 95% CI = 1.15–1.46, and P < 10−3 and OR = 1.33, 95% CI = 1.13–1.56, and P = 0.001, resp.). Conclusion. Both case-control and meta-analyses results revealed the significant association between the E23K variant of KCNJ11 and Type 2 diabetes among Tunisians and Arabs. PMID:25165692

  19. Incidence of X and Y Chromosomal Aneuploidy in a Large Child Bearing Population

    PubMed Central

    Kırkızlar, Eser; Hall, Megan P.; Demko, Zachary; Zneimer, Susan M.; Curnow, Kirsten J.; Gross, Susan; Gropman, Andrea

    2016-01-01

    Background X&Y chromosomal aneuploidies are among the most common human whole-chromosomal copy number changes, but the population-based incidence and prevalence in the child-bearing population is unclear. Methods This retrospective analysis of prospectively collected data leveraged a routine non-invasive prenatal test (NIPT) using parental genotyping to estimate the population-based incidence of X&Y chromosome variations in this population referred for NIPT (generally due to advanced maternal age). Results From 141,916 women and 29,336 men, 119 X&Y chromosomal abnormalities (prevalence: 1 in 1,439) were identified. Maternal findings include: 43 cases of 45,X (40 mosaic); 30 cases of 47,XXX (12 mosaic); 3 cases of 46,XX uniparental disomy; 2 cases of 46,XY/46,XX; 23 cases of mosaicism of unknown type; 2 cases of 47,XX,i(X)(q10). Paternal findings include: 2 cases of 47,XXY (1 mosaic); 10 cases of 47,XYY (1 mosaic); 4 partial Y deletions. Conclusions Single chromosome aneuploidy was present in one of every 1,439 individuals considered in this study, showing 47,XXX; 47,XX,i(X)(q10); 47,XYY; 47,XXY, partial Y deletions, and a high level of mosaicism for 45,X. This expands significantly our understanding of X&Y chromosomal variations and fertility issues, and is critical for families and adults affected by these disorders. This current and extensive information on fertility will be beneficial for genetic counseling on prenatal diagnoses as well as for newly diagnosed postnatal cases. PMID:27512996

  20. Feasibility study for remote assessment of cognitive function in multiple sclerosis.

    PubMed

    George, Michaela F; Holingue, Calliope B; Briggs, Farren B S; Shao, Xiaorong; Bellesis, Kalliope H; Whitmer, Rachel A; Schaefer, Catherine; Benedict, Ralph Hb; Barcellos, Lisa F

    2016-01-01

    Cognitive impairment is common in multiple sclerosis (MS), and affects employment and quality of life. Large studies are needed to identify risk factors for cognitive decline. Currently, a MS-validated remote assessment for cognitive function does not exist. Studies to determine feasibility of large remote cognitive function investigations in MS have not been published. To determine whether MS patients would participate in remote cognitive studies. We utilized the Modified Telephone Interview for Cognitive Status (TICS-M), a previously validated phone assessment for cognitive function in healthy elderly populations to detect mild cognitive impairment. We identified factors that influenced participation rates. We investigated the relationship between MS risk factors and TICS-M score in cases, and score differences between cases and control individuals. The TICS-M was administered to MS cases and controls. Linear and logistic regression models were utilized. 11.5% of eligible study participants did not participate in cognitive testing. MS cases, females and individuals with lower educational status were more likely to refuse (p<0.001). Cases who did complete testing did not differ in terms of perceived cognitive deficit compared to cases that did participate. More severe disease, smoking, and being male were associated with a lower TICS-M score among cases (p<0.001). The TICS-M score was significantly lower in cases compared to controls (p=0.007). Our results demonstrate convincingly that a remotely administered cognitive assessment is quite feasible for conducting large epidemiologic studies in MS, and lay the much needed foundation for future work that will utilize MS-validated cognitive measures.

  1. Feasibility study for remote assessment of cognitive function in multiple sclerosis

    PubMed Central

    George, Michaela F.; Holingue, Calliope B.; Briggs, Farren B.S.; Shao, Xiaorong; Bellesis, Kalliope H.; Whitmer, Rachel A.; Schaefer, Catherine; Benedict, Ralph HB; Barcellos, Lisa F.

    2017-01-01

    Background Cognitive impairment is common in multiple sclerosis (MS), and affects employment and quality of life. Large studies are needed to identify risk factors for cognitive decline. Currently, a MS-validated remote assessment for cognitive function does not exist. Studies to determine feasibility of large remote cognitive function investigations in MS have not been published. Objective To determine whether MS patients would participate in remote cognitive studies. We utilized the Modified Telephone Interview for Cognitive Status (TICS-M), a previously validated phone assessment for cognitive function in healthy elderly populations to detect mild cognitive impairment. We identified factors that influenced participation rates. We investigated the relationship between MS risk factors and TICS-M score in cases, and score differences between cases and control individuals. Methods The TICS-M was administered to MS cases and controls. Linear and logistic regression models were utilized. Results 11.5% of eligible study participants did not participate in cognitive testing. MS cases, females and individuals with lower educational status were more likely to refuse (p<0.001). Cases who did complete testing did not differ in terms of perceived cognitive deficit compared to cases that did participate. More severe disease, smoking, and being male were associated with a lower TICS-M score among cases (p<0.001). The TICS-M score was significantly lower in cases compared to controls (p=0.007). Conclusions Our results demonstrate convincingly that a remotely administered cognitive assessment is quite feasible for conducting large epidemiologic studies in MS, and lay the much needed foundation for future work that will utilize MS-validated cognitive measures. PMID:28255581

  2. Patterns of anti-inflammatory drug use and risk of dementia: a matched case-control study.

    PubMed

    Dregan, A; Chowienczyk, P; Armstrong, D

    2015-11-01

    There is limited primary-care-based evidence about a potential association between anti-inflammatory therapy and dementia subtypes. The present study addressed this limitation by using electronic health records from a large primary care database. A case-control study was implemented using electronic medical records. Cases had a diagnosis of dementia between 1992 and 2014. Up to four controls matched on age, gender, family practice and index date were selected for each case. Use of non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoid drugs represented the exposure variables. Primary outcome measures included all-cause dementia and main dementia subtypes, including Alzheimer disease (AD), vascular dementia (VaD) and Lewy body dementia (LBD). Data were analysed using conditional logistic regression. The study identified 31,083 patients with AD, 23,465 with VaD and 1694 with LBD. Ever-used NSAIDs were associated with a modest increase in the risk of all-cause dementia (odds ratio 1.04, 95% confidence interval 1.02-1.05, P < 0.006), whilst no association was apparent for ever-used glucocorticoids (0.98, 0.96-1.01, P = 0.152). There was no evidence for an association between NSAIDs and AD (1.03, 0.99-1.06, P = 0.07) or LBD (1.13, 0.99-1.29, P = 0.08). However, a significant increase in the risk for VaD (1.33, 1.29-1.38, P < 0.001) was observed. Similar patterns emerged for glucocorticoid therapy. In a large primary care population, there was no robust evidence for a potential association between anti-inflammatory drugs and risk of AD or LBD. NSAIDs and glucocorticoid drugs were associated with higher risk of VaD. © 2015 EAN.

  3. Leveraging public health's participation in a Health Information Exchange to improve communicable disease reporting.

    PubMed

    Painter, Ian; Revere, Debra; Gibson, P Joseph; Baseman, Janet

    2017-01-01

    Infectious diseases can appear and spread rapidly. Timely information about disease patterns and trends allows public health agencies to quickly investigate and efficiently contain those diseases. But disease case reporting to public health has traditionally been paper-based, resulting in somewhat slow, burdensome processes. Fortunately, the expanding use of electronic health records and health information exchanges has created opportunities for more rapid, complete, and easily managed case reporting and investigation. To assess how this new service might impact the efficiency and quality of a public health agency's case investigations, we compared the timeliness of usual case investigation to that of case investigations based on case report forms that were partially pre-populated with electronic data. Between September 2013-March 2014, chlamydia disease report forms for certain clinics in Indianapolis were electronically pre-populated with clinical, lab and patient data available through the Indiana Health Information Exchange, then provided to the patient’s doctor. Doctors could then sign the form and deliver it to public health for investigation and population-level disease tracking. Methods: We utilized a novel matched case analysis of timeliness changes in receipt and processing of communicable disease report forms. Each Chlamydia cases reported with the pre-populated form were matched to cases reported in usual ways. We assessed the time from receipt of the case at the public health agency: 1) inclusion of the case into the public health surveillance system and 2) to close to case. A hierarchical random effects model was used to compare mean difference in each outcome between the target cases and the matched cases, with random intercepts for case. Twenty-one Chlamydia cases were reported to the public health agency using the pre-populated form. Sixteen of these pre-populated form cases were matched to at least one other case, with a mean of 23 matches per case. The mean Reporting Lag for the pre-populated form cases was 2.5 days, which was 2.7 days shorter than the mean Reporting Lag for the matched controls (p = <0.001). The mean time to close a pre-populated form case was 4.7 days, which was 0.2 days shorter than time to close for the matched controls (p = 0.792). Use of pre-populated forms significantly decreased the time it took for the local public health agency to begin documenting and closing chlamydia case investigations. Thoughtful use of electronic health data for case reporting may decrease the per-case workload of public health agencies, and improve the timeliness of information about the pattern and spread of disease.

  4. Association of head circumference and shoulder dystocia in macrosomic neonates.

    PubMed

    Larson, Austin; Mandelbaum, David E

    2013-04-01

    To determine whether asymmetric macrosomia (disproportionately large body size in comparison to head circumference) could be demonstrated in a population of infants suffering shoulder dystocia during delivery relative to those that did not suffer from shoulder dystocia. A case-control study was conducted as a retrospective chart review over 3 years at a large maternity hospital in an urban setting. Among infants over 4,000 g, those that suffered from shoulder dystocia during delivery had a smaller mean head circumference than infants of a similar size that did not suffer from shoulder dystocia. A statistically significant difference was also present when cases of documented gestational diabetes were excluded. Asymmetric macrosomia is more likely to be present in a population of infants who suffered shoulder dystocia during delivery. This knowledge could be used in designing tools to predict which pregnancies are at highest risk for shoulder dystocia during delivery.

  5. Risk of leukaemia and residential exposure to air pollution in an industrial area in Northern Italy: a case-control study.

    PubMed

    Parodi, Stefano; Santi, Irene; Casella, Claudia; Puppo, Antonella; Montanaro, Fabio; Fontana, Vincenzo; Pescetto, Massimiliano; Stagnaro, Emanuele

    2015-01-01

    Leukaemia risk in adult populations exposed to environmental air pollution is poorly investigated. We have carried out a population-based case-control study in an area that included a fossil fuel power plant, a coke oven and two big chemical industries. Information on residential history and several risk factors for leukaemia was obtained from 164 cases, diagnosed between 2002 and 2005, and 279 controls. A higher risk for subjects residing in polluted areas was observed, but statistical significance was not reached (adjusted OR = 1.11 and 1.56 for subjects living in moderately and in heavily polluted zones, respectively, p = 0.190). Results suggest a possible aetiological role of residential air pollution from industrial sites on the risk of developing leukaemia in adult populations. However, the proportion of eligible subjects excluded from the study and the lack of any measure of air pollution prevent definitive conclusions from being drawn.

  6. Polymorphisms in DNA double-strand break repair genes and risk of breast cancer: two population-based studies in USA and Poland, and meta-analyses.

    PubMed

    García-Closas, Montserrat; Egan, Kathleen M; Newcomb, Polly A; Brinton, Louise A; Titus-Ernstoff, Linda; Chanock, Stephen; Welch, Robert; Lissowska, Jolanta; Peplonska, Beata; Szeszenia-Dabrowska, Neonila; Zatonski, Witold; Bardin-Mikolajczak, Alicja; Struewing, Jeffery P

    2006-05-01

    The double-strand break DNA repair pathway has been implicated in breast carcinogenesis. We evaluated the association between 19 polymorphisms in seven genes in this pathway (XRCC2, XRCC3, BRCA2, ZNF350, BRIP1, XRCC4, LIG4) and breast cancer risk in two population-based studies in USA (3,368 cases and 2,880 controls) and Poland (1,995 cases and 2,296 controls). These data suggested weak associations with breast cancer risk for XRCC3 T241M and IVS7-14A>G (pooled odds ratio (95% confidence interval): 1.18 (1.04-1.34) and 0.85 (0.73-0.98) for homozygous variant vs wild-type genotypes, respectively), and for an uncommon variant in ZNF350 S472P (1.24 (1.05-1.48)), with no evidence for study heterogeneity. The remaining variants examined had no significant relationships to breast cancer risk. Meta-analyses of studies in Caucasian populations, including ours, provided some support for a weak association for homozygous variants for XRCC3 T241M (1.16 (1.04-1.30); total of 10,979 cases and 10,423 controls) and BRCA2 N372H (1.13 (1.10-1.28); total of 13,032 cases and 13,314 controls), and no support for XRCC2 R188H (1.06 (0.59-1.91); total of 8,394 cases and 8,404 controls). In conclusion, the genetic variants evaluated are unlikely to have a substantial overall association with breast cancer risk; however, weak associations are possible for XRCC3 (T241M and IVS7-14A>G), BRCA2 N372H, and ZNF350 S472P. Evaluation of potential underlying gene-gene interactions or associations in population subgroups will require even larger sample sizes.

  7. The scaling of contact rates with population density for the infectious disease models.

    PubMed

    Hu, Hao; Nigmatulina, Karima; Eckhoff, Philip

    2013-08-01

    Contact rates and patterns among individuals in a geographic area drive transmission of directly-transmitted pathogens, making it essential to understand and estimate contacts for simulation of disease dynamics. Under the uniform mixing assumption, one of two mechanisms is typically used to describe the relation between contact rate and population density: density-dependent or frequency-dependent. Based on existing evidence of population threshold and human mobility patterns, we formulated a spatial contact model to describe the appropriate form of transmission with initial growth at low density and saturation at higher density. We show that the two mechanisms are extreme cases that do not capture real population movement across all scales. Empirical data of human and wildlife diseases indicate that a nonlinear function may work better when looking at the full spectrum of densities. This estimation can be applied to large areas with population mixing in general activities. For crowds with unusually large densities (e.g., transportation terminals, stadiums, or mass gatherings), the lack of organized social contact structure deviates the physical contacts towards a special case of the spatial contact model - the dynamics of kinetic gas molecule collision. In this case, an ideal gas model with van der Waals correction fits well; existing movement observation data and the contact rate between individuals is estimated using kinetic theory. A complete picture of contact rate scaling with population density may help clarify the definition of transmission rates in heterogeneous, large-scale spatial systems. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Brief Report: Maternal Smoking during Pregnancy and Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Lee, Brian K.; Gardner, Renee M.; Dal, Henrik; Svensson, Anna; Galanti, Maria Rosaria; Rai, Dheeraj; Dalman, Christina; Magnusson, Cecilia

    2012-01-01

    Prenatal exposure to tobacco smoke is suggested as a potential risk factor for autism spectrum disorders (ASD). Previous epidemiological studies of this topic have yielded mixed findings. We performed a case-control study of 3,958 ASD cases and 38,983 controls nested in a large register-based cohort in Sweden. ASD case status was measured using a…

  9. Non-specific effect of measles vaccination on overall child mortality in an area of rural India with high vaccination coverage: a population-based case-control study.

    PubMed

    Kabir, Zubair; Long, Jean; Reddaiah, Vankadara P; Kevany, John; Kapoor, Suresh K

    2003-01-01

    To determine whether vaccination against measles in a population with sustained high vaccination coverage and relatively low child mortality reduces overall child mortality. In April and May 2000, a population-based, case-control study was conducted at Ballabgarh (an area in rural northern India). Eligible cases were 330 children born between 1 January 1991 and 31 December 1998 who died aged 12-59 months. A programme was used to match 320 controls for age, sex, family size, and area of residence from a birth cohort of 15 578 born during the same time period. The analysis used 318 matched pairs and suggested that children aged 12-59 months who did not receive measles vaccination in infancy were three times more likely to die than those vaccinated against measles. Children from lower caste households who were not vaccinated in infancy had the highest risk of mortality (odds ratio, 8.9). A 27% increase in child mortality was attributable to failure to vaccinate against measles in the study population. Measles vaccine seems to have a non-specific reducing effect on overall child mortality in this population. If true, children in lower castes may reap the greatest gains in survival. The findings should be interpreted with caution because the nutritional status of the children was not recorded and may be a residual confounder. "All-cause mortality" is a potentially useful epidemiological endpoint for future vaccine trials.

  10. An Outbreak of Japanese Encephalitis in Adults in Northern China, 2013: A Population-Based Study.

    PubMed

    Li, Xiaolong; Gao, Xiaoyan; Fu, Shihong; Wang, Huanyu; Lu, Zhi; He, Ying; Lei, Wenwen; Liang, Guodong

    2018-05-09

    A Japanese encephalitis (JE) epidemic occurred in 2013 in China. The aim of this study was to determine the spatial-temporal pattern of JE cases in adults occurring in 2013, as well as identify potential hotspots of incidences in the afflicted regions in China. To generate a spatial-temporal pattern of JE cases in China, epidemiological and demographic data between 2011 and 2013 were collected. Our results indicate that the total number of JE cases in 2013 was significantly higher compared with those in 2011 and 2012. While the incidence of JE in individuals aged less than 15 years decreased in 2013, the incidence rate increased substantially in those aged 15 years and older. The population aged over 40 years was associated with the greatest increase of JE. Demographic analysis revealed a consistent increase in the proportion of JE cases aged 15 years and older in 2013 (42%) compared with that in 2012 (15%). In addition, JE cases from areas located between 35°N, 114°E and 40°N, 120°E in northern China were found to account for 27.17% of total JE cases nationwide in 2013, compared with 2.21% and 3.13% in 2011 and 2012, respectively. In these northern regions, the group aged 15 years and older represents the predominant population with JE, accounting for 73% of total cases. Further cluster analysis identified a large number of hotspots of JE in adults (>15 years of age) in northern China. Unlike the JE epidemics primarily in children below 15 years old in southern China, a significant outbreak of JE occurred in northern China in 2013, with the older age groups being the primary population affected. The increasing incidence of JE in adults has become an important public health issue and poses a new challenge to the successful prevention and control of JE in China, as well as other countries in East Asia.

  11. Childhood cancer and residential radon exposure - results of a population-based case-control study in Lower Saxony (Germany).

    PubMed

    Kaletsch, U; Kaatsch, P; Meinert, R; Schüz, J; Czarwinski, R; Michaelis, J

    1999-09-01

    A population-based case-control study on risk factors for childhood malignancies was used to investigate a previously reported association between elevated indoor radon concentrations and childhood cancer, with special regard to leukaemia. The patients were all children suffering from leukaemia and common solid tumours (nephroblastoma, neuroblastoma, rhabdomyosarcoma, central nervous system (CNS) tumours) diagnosed between July 1988 and June 1993 in Lower Saxony (Germany) and aged less than 15 years. Two population-based control groups were matched by age and gender to the leukaemia patients. Long-term (1 year) radon measurements were performed in those homes where the children had been living for at least 1 year, with particular attention being paid to those rooms where they had stayed most of the time. Due to the sequential study design, radon measurements in these rooms could only be done for 36% (82 leukaemias, 82 solid tumours and 209 controls) of the 1038 families initially contacted. Overall mean indoor radon concentrations (27 Bq m(-3)) were low compared with the measured levels in other studies. Using a prespecified cutpoint of 70 Bq m(-3), no association with indoor radon concentrations was seen for the leukaemias (odds ratio (OR): 1.30; 95% confidence interval (95% CI): 0.32-5.33); however, the risk estimates were elevated for the solid tumours (OR: 2.61; 95% CI: 0.96-7.13), mainly based on 6 CNS tumours. We did not find any evidence for an association between indoor radon and childhood leukaemia, which is in line with a recently published American case-control study. There is little support for an association with CNS tumours in the literature.

  12. Lifetime occupational exposure to metals and welding fumes, and risk of glioma: a 7-country population-based case-control study.

    PubMed

    Parent, Marie-Elise; Turner, Michelle C; Lavoué, Jérôme; Richard, Hugues; Figuerola, Jordi; Kincl, Laurel; Richardson, Lesley; Benke, Geza; Blettner, Maria; Fleming, Sarah; Hours, Martine; Krewski, Daniel; McLean, David; Sadetzki, Siegal; Schlaefer, Klaus; Schlehofer, Brigitte; Schüz, Joachim; Siemiatycki, Jack; van Tongeren, Martie; Cardis, Elisabeth

    2017-08-25

    Brain tumor etiology is poorly understood. Based on their ability to pass through the blood-brain barrier, it has been hypothesized that exposure to metals may increase the risk of brain cancer. Results from the few epidemiological studies on this issue are limited and inconsistent. We investigated the relationship between glioma risk and occupational exposure to five metals - lead, cadmium, nickel, chromium and iron- as well as to welding fumes, using data from the seven-country INTEROCC study. A total of 1800 incident glioma cases and 5160 controls aged 30-69 years were included in the analysis. Lifetime occupational exposure to the agents was assessed using the INTEROCC JEM, a modified version of the Finnish job exposure matrix FINJEM. In general, cases had a slightly higher prevalence of exposure to the various metals and welding fumes than did controls, with the prevalence among ever exposed ranging between 1.7 and 2.2% for cadmium to 10.2 and 13.6% for iron among controls and cases, respectively. However, in multivariable logistic regression analyses, there was no association between ever exposure to any of the agents and risk of glioma with odds ratios (95% confidence intervals) ranging from 0.8 (0.7-1.0) for lead to 1.1 (0.7-1.6) for cadmium. Results were consistent across models considering cumulative exposure or duration, as well as in all sensitivity analyses conducted. Findings from this large-scale international study provide no evidence for an association between occupational exposure to any of the metals under scrutiny or welding fumes, and risk of glioma.

  13. Association between prostate cancer and urinary calculi: a population-based study.

    PubMed

    Chung, Shiu-Dong; Liu, Shih-Ping; Lin, Herng-Ching

    2013-01-01

    Understanding the reasons underlying the emerging trend and the changing demographics of Asian prostate cancer (PC) has become an important field of study. This study set out to explore the possibility that urinary calculi (UC) and PC may share an association by conducting a case-control study on a population-based database in Taiwan. The cases of this study included 2,900 subjects ≥ 40 years-old who had received their first-time diagnosis of PC and 14,500 randomly selected controls without PC. Conditional logistic regressions were employed to explore the association between PC and having been previously diagnosed with UC. We found that prior UC was found among 608 (21.0%) cases and 2,037 (14.1%) controls (p<0.001). Conditional logistic regression analysis revealed that compared to controls, the odds ratio (OR) of prior UC for cases was 1.63 (95% CI = 1.47-1.80). Furthermore, we found that cases were more likely to have been previously diagnosed with kidney calculus (OR = 1.71; 95% CI = 1.42-2.05), bladder calculus (OR = 2.06; 95% CI = 1.32-3.23), unspecified calculus (OR = 1.66; 95% CI = 1.37-2.00), and ≥2 locations of UC (OR = 1.73; 1.47-2.02) than controls. However, there was no significant relationship between PC and prior ureter calculus. We also found that of the patients with UC, there was no significant difference between PC and treatment method. This investigation detected an association between PC and prior UC. These results highlight a potential target population for PC screening.

  14. Preoperative Antibiotics and Mortality in the Elderly

    PubMed Central

    Silber, Jeffrey H.; Rosenbaum, Paul R.; Trudeau, Martha E.; Chen, Wei; Zhang, Xuemei; Lorch, Scott A.; Kelz, Rachel Rapaport; Mosher, Rachel E.; Even-Shoshan, Orit

    2005-01-01

    Objective and Background: It is generally thought that the use of preoperative antibiotics reduces the risk of postoperative infection, yet few studies have described the association between preoperative antibiotics and the risk of dying. The objective of this study was to determine whether preoperative antibiotics are associated with a reduced risk of death. Methods: We performed a multivariate matched, population-based, case-control study of death following surgery on 1362 Pennsylvania Medicare patients between 65 and 85 years of age undergoing general and orthopedic surgery. Cases (681 deaths within 60 days from hospital admission) were randomly selected throughout Pennsylvania using claims from 1995 and 1996. Models were developed to scan Medicare claims, looking for controls who did not die and who were the closest matches to the previously selected cases based on preoperative characteristics. Cases and their controls were identified, and charts were abstracted to define antibiotic use and obtain baseline severity adjustment data. Results: For general surgery, the odds of dying within 60 days were less than half in those treated with preoperative antibiotics within 2 hours of incision as compared with those without such treatment: (odds ratio = 0.44; 95% confidence interval, 0.32–0.60), P < 0.0001). For orthopedic surgery, no significant mortality reduction was observed (OR = 0.85; 95% confidence interval, 0.54–1.32; P < 0.464). Interpretation: Preoperative antibiotics are associated with a substantially lower 60-day mortality rate in elderly patients undergoing general surgery. In patients who appear to be comparable, the risk of death was half as large among those who received preoperative antibiotics. PMID:15973108

  15. Association of genetic polymorphisms in matrix metalloproteinase-9 and coronary artery disease in the Chinese Han population: a case-control study.

    PubMed

    Wu, Hai-di; Bai, Xiao; Chen, Dong-mei; Cao, Hong-yan; Qin, Ling

    2013-09-01

    Matrix metalloproteinase-9 (MMP-9) plays an important role in inflammation and matrix degradation involved in atherosclerosis and plaque rupture. The T allele of rs3918242 has been reported to lead to a high promoter activity and associate with the extent of coronary artery disease (CAD). And some studies have reported that the G allele of rs17576 might be associated with CAD. The aim of this study was to assess the association between the polymorphisms of the MMP-9 gene and CAD in the Chinese Han population. This case-control study comprised 258 CAD cases and 153 controls from the Chinese Han Population. The genomic DNA of MMP-9 was isolated from whole blood. Polymerase chain reaction-based restriction fragment length polymorphism was used to determine the rs3918242 and rs17576 genotypes in the MMP-9 gene and the total serum levels of MMP-9 were measured using enzyme-linked immunosorbent assay in both case and control groups. Analysis of MMP-9 gene polymorphisms showed that the frequencies of the T allele and CT+TT genotypes of rs3918242 were significantly higher in the case group than in the control group (p<0.05). However, the distribution of variant genotypes of rs17576 did not differ between the case and control groups (p>0.05). The total serum level of MMP-9 was significantly higher in the case group than in the control group (p<0.05). The subjects carrying T alleles in the CAD group had higher average serum MMP-9 levels compared with CC genotypes (p<0.05). Our results suggest that the single-nucleotide polymorphism of rs3918242 in the MMP-9 gene is associated with CAD and high serum levels of MMP-9 are also associated with CAD in the Chinese Han population. Therefore, genetic variation of rs3918242 may participate in the development of CAD through influencing MMP-9 expression.

  16. Association of Drug and Alcohol Use With Adolescent Firearm Homicide at Individual, Family, and Neighborhood Levels

    PubMed Central

    Hohl, Bernadette C.; Wiley, Shari; Wiebe, Douglas J.; Culyba, Alison J.; Drake, Rebecca; Branas, Charles C.

    2017-01-01

    IMPORTANCE Homicide is the third leading cause of death for adolescents in the United States and the leading cause of death for adolescents who are African American. Large cities have disproportionate homicide rates. OBJECTIVE To determine the relationships between exposures to drugs and alcohol at the individual, family, and neighborhood levels and adolescent firearm homicide and to inform new approaches to preventing firearm violence. DESIGN, SETTING, AND PARTICIPANTS Population-based case-control study from January 2010 to December 2012 of all 13- to 20-year-olds who were homicide victims in Philadelphia during the study period matched to randomly selected 13- to 20-year-old controls from the general population. EXPOSURES Individual drug and alcohol use at the time of injury, history of drug and alcohol use, caregiver drug and alcohol use, and neighborhood availability of alcohol and illegal drugs. We also controlled for age, race, school suspensions, arrests, and neighborhood ethnicity. MAIN OUTCOMES AND MEASURES Adolescent firearm homicide identified from police and medical examiner’s reports. RESULTS We enrolled 161 adolescent homicide cases, including 157 (97.5%) firearm homicide cases and 172 matched controls, including 166 (96.5%) firearm homicide controls. Adolescents with a history of alcohol use (adjusted odds ratio [AOR], 4.1; 95% CI, 1.2–14.0) or drug use (AOR, 4.4; 95% CI, 1.7–11.6) had increased odds of firearm homicide. Adolescents whose caregiver had a history of drug use had increased odds of firearm homicide (AOR, 11.7; 95% CI, 2.8–48.0). Adolescents in neighborhoods with high densities of alcohol outlets (AOR, 3.2; 95% CI, 1.1–9.1) and moderate or high drug availability had increased odds of firearm homicide (AOR, 3.4; 95% CI, 1.1–10.3 vs AOR, 7.5; 95% CI, 2.2–25.8). CONCLUSIONS AND RELEVANCE Almost all adolescent homicides in Philadelphia between 2010 and 2012 were committed with a firearm. Substance use at the individual, family, and neighborhood levels was associated with increased odds of adolescent firearm homicide; drug use was associated at all 3 levels and alcohol at the individual and neighborhood levels. Expanding violence prevention efforts to target drug and alcohol use at multiple levels may help to reduce the firearm violence that disproportionately affects adolescents in minority populations in large US cities. PMID:28055064

  17. Occupational exposure to asbestos and risk of cholangiocarcinoma: a population-based case–control study in four Nordic countries

    PubMed Central

    Farioli, Andrea; Straif, Kurt; Brandi, Giovanni; Curti, Stefania; Kjaerheim, Kristina; Martinsen, Jan Ivar; Sparen, Pär; Tryggvadottir, Laufey; Weiderpass, Elisabete; Biasco, Guido; Violante, Francesco Saverio; Mattioli, Stefano; Pukkala, Eero

    2018-01-01

    Objectives To assess the association between occupational exposure to asbestos and the risk of cholangiocarcinoma (CC). Methods We conducted a case–control study nested in the Nordic Occupational Cancer (NOCCA) cohort. We studied 1458 intrahepatic CC (ICC) and 3972 extrahepatic CC (ECC) cases occurring among subjects born in 1920 or later in Finland, Iceland, Norway and Sweden. Each case was individually matched by birth year, gender and country to five population controls. The cumulative exposure to asbestos (measured in fibres (f)/ml × years) was assessed by applying the NOCCA job-exposure matrix to data on occupations collected during national population censuses (conducted in 1960, 1970, 1980/81 and 1990). Odds ratios (OR) and 95% CI were estimated using conditional logistic regression models adjusted by printing industry work. Results We observed an increasing risk of ICC with cumulative exposure to asbestos: never exposed, OR 1.0 (reference category); 0.1–4.9 f/mL × years, OR 1.1 (95% CI 0.9 to 1.3); 5.0–9.9 f/mL × years, OR 1.3 (95% CI 0.9 to 2.1); 10.0–14.9 f/mL × years, OR 1.6 (95% CI 1.0 to 2.5); ≥15.0 f/mL × years, OR 1.7 (95% CI 1.1 to 2.6). We did not observe an association between cumulative asbestos exposure and ECC. Conclusions Our study provides evidence that exposure to asbestos might be a risk factor for ICC. Our findings also suggest that the association between ECC and asbestos is null or weaker than that observed for ICC. Further studies based on large industrial cohorts of asbestos workers and possibly accounting for personal characteristics and clinical history are needed. PMID:29133597

  18. Risk factors for squamous cell carcinoma of the penis--population-based case-control study in Denmark.

    PubMed

    Madsen, Birgitte Schütt; van den Brule, Adriaan J C; Jensen, Helle Lone; Wohlfahrt, Jan; Frisch, Morten

    2008-10-01

    Few etiologic studies of squamous cell carcinoma (SCC) of the penis have been carried out in populations where childhood circumcision is rare. A total of 71 patients with invasive (n=53) or in situ (n=18) penile SCC, 86 prostate cancer controls, and 103 population controls were interviewed in a population-based case-control study in Denmark. For 37 penile SCC patients, tissue samples were PCR examined for human papillomavirus (HPV) DNA. Overall, 65% of PCR-examined penile SCCs were high-risk HPV-positive, most of which (22 of 24; 92%) were due to HPV16. Penile SCC risk was positively associated with measures of early and high sexual activity, including lifetime number of female sex partners, number of female sex partners before age 20, age at first intercourse, penile-oral sex, a history of anogenital warts, and never having used condoms. Histories of phimosis and priapism at least 5 years before diagnosis were also significant risk factors, whereas alcohol abstinence was associated with reduced risk. Our study confirms sexually transmitted HPV16 infection and phimosis as major risk factors for penile SCC and suggests that penile-oral sex may be an important means of viral transmission. The association with priapism was unexpected and needs replication.

  19. The Fraction of Cancer Attributable to Ways of Life, Infections, Occupation, and Environmental Agents in Brazil in 2020

    PubMed Central

    Azevedo e Silva, Gulnar; de Moura, Lenildo; Curado, Maria Paula; Gomes, Fabio da Silva; Otero, Ubirani; de Rezende, Leandro Fórnias Machado; Daumas, Regina Paiva; Guimarães, Raphael Mendonça; Meira, Karina Cardoso; Leite, Iuri da Costa; Valente, Joaquim Gonçalves; Moreira, Ronaldo Ismério; Koifman, Rosalina; Malta, Deborah Carvalho; Mello, Marcia Sarpa de Campos; Guedes, Thiago Wagnos Guimarães; Boffetta, Paolo

    2016-01-01

    Many human cancers develop as a result of exposure to risk factors related to the environment and ways of life. The aim of this study was to estimate attributable fractions of 25 types of cancers resulting from exposure to modifiable risk factors in Brazil. The prevalence of exposure to selected risk factors among adults was obtained from population-based surveys conducted from 2000 to 2008. Risk estimates were based on data drawn from meta-analyses or large, high quality studies. Population-attributable fractions (PAF) for a combination of risk factors, as well as the number of preventable deaths and cancer cases, were calculated for 2020. The known preventable risk factors studied will account for 34% of cancer cases among men and 35% among women in 2020, and for 46% and 39% deaths, respectively. The highest attributable fractions were estimated for tobacco smoking, infections, low consumption of fruits and vegetables, excess weight, reproductive factors, and physical inactivity. This is the first study to systematically estimate the fraction of cancer attributable to potentially modifiable risk factors in Brazil. Strategies for primary prevention of tobacco smoking and control of infection and the promotion of a healthy diet and physical activity should be the main priorities in policies for cancer prevention in the country. PMID:26863517

  20. Genotyping and inflated type I error rate in genome-wide association case/control studies

    PubMed Central

    Sampson, Joshua N; Zhao, Hongyu

    2009-01-01

    Background One common goal of a case/control genome wide association study (GWAS) is to find SNPs associated with a disease. Traditionally, the first step in such studies is to assign a genotype to each SNP in each subject, based on a statistic summarizing fluorescence measurements. When the distributions of the summary statistics are not well separated by genotype, the act of genotype assignment can lead to more potential problems than acknowledged by the literature. Results Specifically, we show that the proportions of each called genotype need not equal the true proportions in the population, even as the number of subjects grows infinitely large. The called genotypes for two subjects need not be independent, even when their true genotypes are independent. Consequently, p-values from tests of association can be anti-conservative, even when the distributions of the summary statistic for the cases and controls are identical. To address these problems, we propose two new tests designed to reduce the inflation in the type I error rate caused by these problems. The first algorithm, logiCALL, measures call quality by fully exploring the likelihood profile of intensity measurements, and the second algorithm avoids genotyping by using a likelihood ratio statistic. Conclusion Genotyping can introduce avoidable false positives in GWAS. PMID:19236714

  1. Long-term mobile phone use and brain tumor risk.

    PubMed

    Lönn, Stefan; Ahlbom, Anders; Hall, Per; Feychting, Maria

    2005-03-15

    Handheld mobile phones were introduced in Sweden during the late 1980s. The purpose of this population-based, case-control study was to test the hypothesis that long-term mobile phone use increases the risk of brain tumors. The authors identified all cases aged 20-69 years who were diagnosed with glioma or meningioma during 2000-2002 in certain parts of Sweden. Randomly selected controls were stratified on age, gender, and residential area. Detailed information about mobile phone use was collected from 371 (74%) glioma and 273 (85%) meningioma cases and 674 (71%) controls. For regular mobile phone use, the odds ratio was 0.8 (95% confidence interval: 0.6, 1.0) for glioma and 0.7 (95% confidence interval: 0.5, 0.9) for meningioma. Similar results were found for more than 10 years' duration of mobile phone use. No risk increase was found for ipsilateral phone use for tumors located in the temporal and parietal lobes. Furthermore, the odds ratio did not increase, regardless of tumor histology, type of phone, and amount of use. This study includes a large number of long-term mobile phone users, and the authors conclude that the data do not support the hypothesis that mobile phone use is related to an increased risk of glioma or meningioma.

  2. Estimation of the marginal effect of regular drug use on multiple sclerosis in the Iranian population.

    PubMed

    Abdollahpour, Ibrahim; Nedjat, Saharnaz; Mansournia, Mohammad Ali; Schuster, Tibor

    2018-01-01

    There are only few reports regarding the role of lifetime drug or substance use in multiple sclerosis (MS) etiology. In this study, we investigated the potential effect of drug or substance exposure on the onset of MS diagnosis. We conducted a population-based incident case control study in Tehran. Cases (n = 547) were 15-50 years old persons with MS identified from the Iranian Multiple Sclerosis Society (IMSS) register during August 7, 2013, and November 17, 2015. Population-based controls (n = 1057) were 15-50 years old and were recruited by random digit telephone dialing. Inverse-probability-of-treatment weighing (IPTW) using two sets of propensity scores (PSs) was used to estimate marginal incidence odds ratios (ORs) for MS contrasting pre-specified substance use. The estimated marginal OR was 6.03 (95% confidence interval: 3.54;10.3, using trimmed weights at the 95th percentile of the stabilized weight distribution) in both IPTW analyses comparing lifetime substance use (opioids, cannabis, inhalants, hallucinogens and stimulants) for at least one time monthly during a six-months or longer period vs. no such history of drug use. Subject to limitation of causal claims based on case-control studies, this study suggests that monthly drug or substance use for a period of at least six consecutive months, may increase the risk of MS by factor 3.5 or higher.

  3. Dietary factors and the risk of glioma in adults: results of a case-control study in Melbourne, Australia.

    PubMed

    Giles, G G; McNeil, J J; Donnan, G; Webley, C; Staples, M P; Ireland, P D; Hurley, S F; Salzberg, M

    1994-11-01

    In a population-based case-control study of 416 incident gliomas in adults carried out in Melbourne, Australia, between 1987 and 1991, 409 age-sex-matched case-control pairs (243 male and 166 female) had adequate data available to examine associations between the dietary intake of N-nitroso compounds, N-nitroso precursors, other nutrients including N-nitroso inhibitors, and the risk of glioma. Dietary intakes were based on the reported frequency of consumption of 59 food items. Increased odds ratio (OR) were observed in males who consumed high levels of bacon, corned meats, apples, melons and oil. OR less than unity were observed in men consuming cabbage and cola drinks, and in women who consumed wholegrain bread, pasta, corned meat, bananas, cauliflower, brocoli, cola drinks and nuts. Generally, N-nitroso associations were greater in men and micronutrient associations were greater in women. Elevated OR in men, but not women, were associated with the intake of N-nitroso dimethylamine (NDMA), retinol and vitamin E. The intake of nitrate (largely of vegetable origin) was protective in women but not in men. When analyzed using multiple logistic regression, the association with NDMA intake in males was not modified by dietary micronutrient intakes. In females, beta carotene alone, though not directly associated with risk, modified the effect of NDMA. On balance, this study added only limited support to the N-nitroso hypothesis of glial carcinogenesis.

  4. Hyponatremia Is Associated With Increased Osteoporosis and Bone Fractures in a Large US Health System Population.

    PubMed

    Usala, Rachel L; Fernandez, Stephen J; Mete, Mihriye; Cowen, Laura; Shara, Nawar M; Barsony, Julianna; Verbalis, Joseph G

    2015-08-01

    The significance of studies suggesting an increased risk of bone fragility fractures with hyponatremia through mechanisms of induced bone loss and increased falls has not been demonstrated in large patient populations with different types of hyponatremia. This matched case-control study evaluated the effect of hyponatremia on osteoporosis and fragility fractures in a patient population of more than 2.9 million. Osteoporosis (n = 30 517) and fragility fracture (n = 46 256) cases from the MedStar Health database were matched on age, sex, race, and patient record length with controls without osteoporosis (n = 30 517) and without fragility fractures (n = 46 256), respectively. Cases without matched controls or serum sodium (Na(+)) data or with Na(+) with a same-day blood glucose greater than 200 mg/dL were excluded. Incidence of diagnosis of osteoporosis and fragility fractures of the upper or lower extremity, pelvis, and vertebrae were the outcome measures. Multivariate conditional logistic regression models demonstrated that hyponatremia was associated with osteoporosis and/or fragility fractures, including chronic [osteoporosis: odds ratio (OR) 3.97, 95% confidence interval (CI) 3.59-4.39; fracture: OR 4.61, 95% CI 4.15-5.11], recent (osteoporosis: OR 3.06, 95% CI 2.81-3.33; fracture: OR 3.05, 95% CI 2.83-3.29), and combined chronic and recent hyponatremia (osteoporosis: OR 12.09, 95% CI 9.34-15.66; fracture: OR 11.21, 95% CI 8.81-14.26). Odds of osteoporosis or fragility fracture increased incrementally with categorical decrease in median serum Na(+). These analyses support the hypothesis that hyponatremia is a risk factor for osteoporosis and fracture. Additional studies are required to evaluate whether correction of hyponatremia will improve patient outcomes.

  5. Direct medical costs of constipation in children over 15 years: a population-based birth cohort

    PubMed Central

    Choung, Rok Seon; Shah, Nilay D.; Chitkara, Denesh; Branda, Megan E.; Van Tilburg, Miranda A.; Whitehead, William E.; Katusic, Slavica K.; Locke, G. Richard; Talley, Nicholas J.

    2011-01-01

    Background Although direct medical costs for constipation-related medical visits are thought to be high, to date there have been no studies examining if longitudinal resource utilization is persistently elevated in children with constipation. Our aim was to estimate the incremental direct medical costs and types of health care utilization associated with constipation from childhood to early adulthood. Methods A nested case-control study was conducted to evaluate the incremental costs associated with constipation. The original sample consisted of 5,718 children in a population-based birth cohort who were born during 1976–1982 in Rochester, MN. The cases included individuals who presented to medical facilities with constipation. The controls were matched and randomly selected among all non-cases in the sample. Direct medical costs for cases and controls were collected from the time subjects were between 5–18 years of age or until the subject emigrated from the community. Results We identified 250 cases with a diagnosis of constipation in the birth cohort. While the mean inpatient costs for cases were $9994 (95% CI=2538, 37201) compared to $2391 (95% CI=923, 7452) for controls (p=0.22) over the time period, the mean outpatient costs for cases were $13927 (95% CI=11325, 16525) compared to $3448 (95% CI=3771, 4621) for controls (p<0.001) over the same time period. The mean annual number emergency department visits for cases were 0.66 (95% CI=0.62, 0.70) compared to 0.34 (95% CI=0.32, 0.35) for controls (p<0.0001). Conclusion Individuals with constipation have higher medical care utilization. Outpatient costs and ER utilization were significantly greater for individuals with constipation from childhood to early adulthood. PMID:20890220

  6. Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population.

    PubMed

    Yu, H; Yan, H; Li, J; Li, Z; Zhang, X; Ma, Y; Mei, L; Liu, C; Cai, L; Wang, Q; Zhang, F; Iwata, N; Ikeda, M; Wang, L; Lu, T; Li, M; Xu, H; Wu, X; Liu, B; Yang, J; Li, K; Lv, L; Ma, X; Wang, C; Li, L; Yang, F; Jiang, T; Shi, Y; Li, T; Zhang, D; Yue, W

    2017-07-01

    Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 × 10 -12 , odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 × 10 -10 , OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 × 10 -10 , OR=0.87; rs10883765 at an intron of ARL3, P=3.06 × 10 -9 , OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case-control status in the Chinese population (Nagelkerke R 2 : 1.7% ~5.7%). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.

  7. Partial AZFc duplications not deletions are associated with male infertility in the Yi population of Yunnan Province, China.

    PubMed

    Ye, Jun-jie; Ma, Li; Yang, Li-juan; Wang, Jin-huan; Wang, Yue-li; Guo, Hai; Gong, Ning; Nie, Wen-hui; Zhao, Shu-hua

    2013-09-01

    There are many reports on associations between spermatogenesis and partial azoospermia factor c (AZFc) deletions as well as duplications; however, results are conflicting, possibly due to differences in methodology and ethnic background. The purpose of this study is to investigate the association of AZFc polymorphisms and male infertility in the Yi ethnic population, residents within Yunnan Province, China. A total of 224 infertile patients and 153 fertile subjects were selected in the Yi ethnic population. The study was performed by sequence-tagged site plus/minus (STS+/-) analysis followed by gene dosage and gene copy definition analysis. Y haplotypes of 215 cases and 115 controls were defined by 12 binary markers using single nucleotide polymorphism on Y chromosome (Y-SNP) multiplex assays based on single base primer extension technology. The distribution of Y haplotypes was not significantly different between the case and control groups. The frequencies of both gr/gr (7.6% vs. 8.5%) and b2/b3 (6.3% vs. 8.5%) deletions do not show significant differences. Similarly, single nucleotide variant (SNV) analysis shows no significant difference of gene copy definition between the cases and controls. However, the frequency of partial duplications in the infertile group (4.0%) is significantly higher than that in the control group (0.7%). Further, we found a case with sY1206 deletion which had two CDY1 copies but removed half of DAZ genes. Our results show that male infertility is associated with partial AZFc duplications, but neither gr/gr nor b2/b3 deletions, suggesting that partial AZFc duplications rather than deletions are risk factors for male infertility in Chinese-Yi population.

  8. Sensitive response of a model of symbiotic ecosystem to seasonal periodic drive

    NASA Astrophysics Data System (ADS)

    Rekker, A.; Lumi, N.; Mankin, R.

    2014-11-01

    A symbiotic ecosysytem (metapopulation) is studied by means of the stochastic Lotka-Volterra model with generalized Verhulst self-regulation. The effect of variable environment on the carrying capacities of populations is taken into account as an asymmetric dichotomous noise and as a deterministic periodic stimulus. In the framework of the mean-field theory an explicit self-consistency equation for the system in the long-time limit is presented. Also, expressions for the probability distribution and for the moments of the population size are found. In certain cases the mean population size exhibits large oscillations in time, even if the amplitude of the seasonal environmental drive is small. Particularly, it is shown that the occurrence of large oscillations of the mean population size can be controlled by noise parameters (such as amplitude and correlation time) and by the coupling strength of the symbiotic interaction between species.

  9. Biomarkers of Alzheimer’s Disease Among Mexican Americans

    PubMed Central

    O’Bryant, Sid E.; Xiao, Guanghua; Edwards, Melissa; Devous, Michael; Gupta, Veer Bala; Martins, Ralph; Zhang, Fan; Barber, Robert

    2013-01-01

    Background Mexican Americans are the fastest aging segment of the U.S. population yet little scientific literature exists regarding the Alzheimer disease (AD) among this segment of the population. The extant literature suggests that biomarkers of AD will vary according to race/ethnicity though no prior work has explicitly studied this possibility. The aim of this study was to create a serum-based biomarker profile of AD among Mexican American. Methods Data were analyzed from 363 Mexican American participants (49 AD and 314 normal controls) enrolled in the Texas Alzheimer’s Research & Care Consortium (TARCC). Non-fasting serum samples were analyzed using a luminex-based multi-plex platform. A biomarker profile was generated using random forest analyses. Results The biomarker profile of AD among Mexican Americans was different from prior work from non-Hispanic populations with regards to the variable importance plots. In fact, many of the top markers were related to metabolic factors (e.g. FABP, GLP-1, CD40, pancreatic polypeptide, insulin-like-growth factor, and insulin). The biomarker profile was a significant classifier of AD status yielding an area under the receiver operating characteristic curve (AUC), sensitivity (SN) and specificity (SP) of 0.77, 0.92 and 0.64, respectively. Combining biomarkers with clinical variables yielded a better balance of SN and SP. Conclusion The biomarker profile for AD among Mexican American cases is significantly different from that previously identified among non-Hispanic cases from many large-scale studies. This is the first study to explicitly examine and provide support for blood-based biomarkers of AD among Mexican Americans. Areas for future research are highlighted. PMID:23313927

  10. Socioeconomic Status and Childhood Leukemia Incidence in Switzerland

    PubMed Central

    Adam, Martin; Kuehni, Claudia E.; Spoerri, Adrian; Schmidlin, Kurt; Gumy-Pause, Fabienne; Brazzola, Pierluigi; Probst-Hensch, Nicole; Zwahlen, Marcel

    2015-01-01

    Socioeconomic status (SES) discrepancies exist for child and adult cancer morbidity and are a major public health concern. In this Swiss population-based matched case–control study on the etiology of childhood leukemia, we selected the cases from the Swiss Childhood Cancer Registry diagnosed since 1991 and the controls randomly from census. We assigned eight controls per case from the 1990 and 2000 census and matched them by the year of birth and gender. SES information for both cases and controls was obtained from census records by probabilistic record linkage. We investigated the association of SES with childhood leukemia in Switzerland, and explored whether it varied with different definitions of socioeconomic status (parental education, living condition, area-based SES), time period, and age. In conditional logistic regression analyses of 565 leukemia cases and 4433 controls, we found no consistent evidence for an association between SES and childhood leukemia. The odds ratio comparing the highest with the lowest SES category ranged from 0.95 (95% CI: 0.71–1.26; Ptrend = 0.73) for paternal education to 1.37 (1.00–1.89; Ptrend = 0.064) for maternal education. No effect modification was found for time period and age at diagnosis. Based on this population-based study, which avoided participation and reporting bias, we assume the potential association of socioeconomic status and childhood leukemia if existing to be small. This study did not find evidence that socioeconomic status, of Switzerland or comparable countries, is a relevant risk factor or strong confounder in etiological investigations on childhood leukemia. PMID:26175964

  11. Genetic Classification of Populations Using Supervised Learning

    PubMed Central

    Bridges, Michael; Heron, Elizabeth A.; O'Dushlaine, Colm; Segurado, Ricardo; Morris, Derek; Corvin, Aiden; Gill, Michael; Pinto, Carlos

    2011-01-01

    There are many instances in genetics in which we wish to determine whether two candidate populations are distinguishable on the basis of their genetic structure. Examples include populations which are geographically separated, case–control studies and quality control (when participants in a study have been genotyped at different laboratories). This latter application is of particular importance in the era of large scale genome wide association studies, when collections of individuals genotyped at different locations are being merged to provide increased power. The traditional method for detecting structure within a population is some form of exploratory technique such as principal components analysis. Such methods, which do not utilise our prior knowledge of the membership of the candidate populations. are termed unsupervised. Supervised methods, on the other hand are able to utilise this prior knowledge when it is available. In this paper we demonstrate that in such cases modern supervised approaches are a more appropriate tool for detecting genetic differences between populations. We apply two such methods, (neural networks and support vector machines) to the classification of three populations (two from Scotland and one from Bulgaria). The sensitivity exhibited by both these methods is considerably higher than that attained by principal components analysis and in fact comfortably exceeds a recently conjectured theoretical limit on the sensitivity of unsupervised methods. In particular, our methods can distinguish between the two Scottish populations, where principal components analysis cannot. We suggest, on the basis of our results that a supervised learning approach should be the method of choice when classifying individuals into pre-defined populations, particularly in quality control for large scale genome wide association studies. PMID:21589856

  12. Population-centered Risk- and Evidence-based Dental Interprofessional Care Team (PREDICT): study protocol for a randomized controlled trial.

    PubMed

    Cunha-Cruz, Joana; Milgrom, Peter; Shirtcliff, R Michael; Bailit, Howard L; Huebner, Colleen E; Conrad, Douglas; Ludwig, Sharity; Mitchell, Melissa; Dysert, Jeanne; Allen, Gary; Scott, JoAnna; Mancl, Lloyd

    2015-06-20

    To improve the oral health of low-income children, innovations in dental delivery systems are needed, including community-based care, the use of expanded duty auxiliary dental personnel, capitation payments, and global budgets. This paper describes the protocol for PREDICT (Population-centered Risk- and Evidence-based Dental Interprofessional Care Team), an evaluation project to test the effectiveness of new delivery and payment systems for improving dental care and oral health. This is a parallel-group cluster randomized controlled trial. Fourteen rural Oregon counties with a publicly insured (Medicaid) population of 82,000 children (0 to 21 years old) and pregnant women served by a managed dental care organization are randomized into test and control counties. In the test intervention (PREDICT), allied dental personnel provide screening and preventive services in community settings and case managers serve as patient navigators to arrange referrals of children who need dentist services. The delivery system intervention is paired with a compensation system for high performance (pay-for-performance) with efficient performance monitoring. PREDICT focuses on the following: 1) identifying eligible children and gaining caregiver consent for services in community settings (for example, schools); 2) providing risk-based preventive and caries stabilization services efficiently at these settings; 3) providing curative care in dental clinics; and 4) incentivizing local delivery teams to meet performance benchmarks. In the control intervention, care is delivered in dental offices without performance incentives. The primary outcome is the prevalence of untreated dental caries. Other outcomes are related to process, structure and cost. Data are collected through patient and staff surveys, clinical examinations, and the review of health and administrative records. If effective, PREDICT is expected to substantially reduce disparities in dental care and oral health. PREDICT can be disseminated to other care organizations as publicly insured clients are increasingly served by large practice organizations. ClinicalTrials.gov NCT02312921 6 December 2014. The Robert Wood Johnson Foundation and Advantage Dental Services, LLC, are supporting the evaluation.

  13. Randomization-Based Inference about Latent Variables from Complex Samples: The Case of Two-Stage Sampling

    ERIC Educational Resources Information Center

    Li, Tiandong

    2012-01-01

    In large-scale assessments, such as the National Assessment of Educational Progress (NAEP), plausible values based on Multiple Imputations (MI) have been used to estimate population characteristics for latent constructs under complex sample designs. Mislevy (1991) derived a closed-form analytic solution for a fixed-effect model in creating…

  14. Mild asthma and chronic bronchitis seem to influence functional exercise capacity: a multi-case control study.

    PubMed

    Marcon, Alessandro; Girardi, Paolo; Ferrari, Marcello; Olivieri, Mario; Accordini, Simone; Bombieri, Cristina; Bortolami, Oscar; Braggion, Marco; Cappa, Veronica; Cazzoletti, Lucia; Locatelli, Francesca; Nicolis, Morena; Perbellini, Luigi; Sembeni, Silvia; Verlato, Giuseppe; Zanolin, Maria Elisabetta; de Marco, Roberto

    2013-01-01

    In the Genes Environment Interaction in Respiratory Diseases population-based multi-case control study, we investigated whether asthma, chronic bronchitis (CB) and rhinitis were associated with a reduced 6-minute walk distance (6MWD), and whether the 6MWD determinants were similar for subjects with/without respiratory diseases. Cases of asthma (n = 360), CB (n = 120), rhinitis (n = 203) and controls (no respiratory diseases: n = 302) were recruited. The variation in the 6MWD across the groups was analyzed by ANCOVA, adjusting for gender, age, height, weight and comorbidity. The 6MWD determinants were studied by linear regression, and heterogeneity across the cases and controls was investigated. The 6MWD differed across cases and controls (p = 0.01). It was shorter for cases of asthma (-17.1, 95% CI -28.3 to -5.8 m) and CB (-20.7, 95% CI: -36.6 to -4.8 m) than for controls (604 ± 68 m on average), but not for cases of rhinitis. The negative association between age and the 6MWD was significant for cases of CB, but not for the other groups (p = 0.001). Even at the level of severity found in the general population, asthma and CB could influence the 6MWD, which seems to reflect the functional exercise level for daily physical activities. The negative association between ageing and the 6MWD was particularly strong in subjects with CB. Our report adds to the mounting evidence that CB is not a trivial condition, especially in the ageing adult population, and it supports the importance of monitoring functional capacity and of physical reconditioning in mild asthma. Copyright © 2013 S. Karger AG, Basel.

  15. Association of IL-10-1082 G/G genotype with lower mortality of acute respiratory distress syndrome in a Chinese population.

    PubMed

    Jin, Xiaodong; Hu, Zhi; Kang, Yan; Liu, Chang; Zhou, Yongfang; Wu, Xiaodong; Liu, Jin; Zhong, Mingxing; Luo, Chuanxing; Deng, Lijing; Deng, Yiyun; Xie, Xiaoqi; Zhang, Zhongwei; Zhou, Yan; Liao, Xuelian

    2012-01-01

    We aimed to investigate whether interleukin-10 (IL-10) -1082 G/G genotype is associated with lower mortality of acute respiratory distress syndrome (ARDS) in a Chinese population. A hospital-based case-control study was conducted in 314 cases of ARDS and 210 controls who were admitted to an intensive care unit with sepsis, trauma, aspiration or massive transfusions. Cases were followed for 30-day mortality. The -1082G/G genotype was associated with lower development of ARDS (OR=0.51; 95% CI 0.34-0.76; P=0.001). Among patients with ARDS, the -1082G/G genotype was associated with lower 30-day mortality (OR=0.44; 95% CI 0.25-0.76; P=0.003). In conclusion, IL-10-1082 G/G genotype is associated with lower development and mortality of ARDS in a Chinese population.

  16. Interleukin 1 beta gene and risk of schizophrenia: detailed case-control and family-based studies and an updated meta-analysis.

    PubMed

    Shibuya, Masako; Watanabe, Yuichiro; Nunokawa, Ayako; Egawa, Jun; Kaneko, Naoshi; Igeta, Hirofumi; Someya, Toshiyuki

    2014-01-01

    Interleukin-1 beta (IL-1β) has been implicated in the pathophysiology of schizophrenia. To assess whether the IL1B gene confers increased susceptibility to schizophrenia, we conducted case-control and family-based studies and an updated meta-analysis. We tested the association between IL1B and schizophrenia in 1229 case-control and 112 trio samples using 12 markers, including common tagging single nucleotide variations (SNVs) and a rare non-synonymous variation detected by resequencing the coding regions. We also performed a meta-analysis of rs16944 using a total of 8724 case-control and 201 trio samples from 16 independent populations. We found no significant associations between any of the 12 SNVs examined and schizophrenia in either case-control or trio samples. Moreover, our meta-analysis results showed no significant association between the common SNV, rs16944, and schizophrenia. The present study does not support a role for IL1B in schizophrenia susceptibility.

  17. Trend of application of World Health Organization control strategy of tuberculosis in Egypt.

    PubMed

    Saad-Hussein, Amal; Mohammed, Asmaa M

    2014-09-01

    World Health Organization (WHO) control policy for tuberculosis (TB) includes Bacillus Calmette-Guérin (BCG) vaccine at birth, case detection, and treatment of cases with directly observed therapy short-course (DOTS). This policy has been applied through the Ministry of Health and Population in Egypt for more than 30years. The controversies about the efficacy of the BCG vaccination against TB in adults initiate some suggestions for its discontinuation from compulsory vaccinations in countries with low incidence of TB. The present work aimed to study the trend of applying the WHO control policy for TB in Egypt among the Egyptian population throughout the last 20years (1992-2011). The documented database of the country, bibliographic review on MEDLINE, published studies and reports, WHO and EMRO databases that covered the period from 1992 to 2011 were used in this study. The incidence rate of all forms of TB (pulmonary and extrapulmonary) dropped by 50% from 34 cases to 17 cases per 100,000 population, as well as the prevalence rate declined by 60.6% from 71 cases per 100,000 population throughout the last 20years. Case detection and treatment success rates have increased throughout the studied period while it flat-lined over the past 6years which may need attention. The results of this study introduce an evidence-based recommendation for continuation of the WHO TB control policy in Egypt towards elimination of the disease. Copyright © 2014 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  18. Productivity losses in chronic obstructive pulmonary disease: a population-based survey.

    PubMed

    Erdal, Marta; Johannessen, Ane; Askildsen, Jan Erik; Eagan, Tomas; Gulsvik, Amund; Grønseth, Rune

    2014-01-01

    We aimed to estimate incremental productivity losses (sick leave and disability) of spirometry-defined chronic obstructive pulmonary disease (COPD) in a population-based sample and in hospital-recruited patients with COPD. Furthermore, we examined predictors of productivity losses by multivariate analyses. We performed four quarterly telephone interviews of 53 and 107 population-based patients with COPD and controls, as well as 102 hospital-recruited patients with COPD below retirement age. Information was gathered regarding annual productivity loss, exacerbations of respiratory symptoms and comorbidities. Incremental productivity losses were estimated by multivariate quantile median regression according to the human capital approach, adjusting for sex, age, smoking habits, education and lung function. Main effect variables were COPD/control status, number of comorbidities and exacerbations of respiratory symptoms. Altogether 55%, 87% and 31% of population-based COPD cases, controls and hospital patients, respectively, had a paid job at baseline. The annual incremental productivity losses were 5.8 (95% CI 1.4 to 10.1) and 330.6 (95% CI 327.8 to 333.3) days, comparing population-recruited and hospital-recruited patients with COPD to controls, respectively. There were significantly higher productivity losses associated with female sex and less education. Additional adjustments for comorbidities, exacerbations and FEV1% predicted explained all productivity losses in the population-based sample, as well as nearly 40% of the productivity losses in hospital-recruited patients. Annual incremental productivity losses were more than 50 times higher in hospital-recruited patients with COPD than that of population-recruited patients with COPD. To ensure a precise estimation of societal burden, studies on patients with COPD should be population-based.

  19. Use of Patients With Diarrhea Who Test Negative for Rotavirus as Controls to Estimate Rotavirus Vaccine Effectiveness Through Case-Control Studies.

    PubMed

    Tate, Jacqueline E; Patel, Manish M; Cortese, Margaret M; Payne, Daniel C; Lopman, Benjamin A; Yen, Catherine; Parashar, Umesh D

    2016-05-01

    Case-control studies are often performed to estimate postlicensure vaccine effectiveness (VE), but the enrollment of controls can be challenging, time-consuming, and costly. We evaluated whether children enrolled in the same hospital-based diarrheal surveillance used to identify rotavirus cases but who test negative for rotavirus (test-negative controls) can be considered a suitable alternative to nondiarrheal hospital or community-based control groups (traditional controls). We compared calculated VE estimates as a function of varying values of true VE, attack rates of rotavirus and nonrotavirus diarrhea in the population, and sensitivity and specificity of the rotavirus enzyme immunoasssay. We also searched the literature to identify rotavirus VE studies that used traditional and test-negative control groups and compared VE estimates obtained using the different control groups. Assuming a 1% attack rate for severe rotavirus diarrhea, a 3% attack rate for severe nonrotavirus diarrhea in the population, a test sensitivity of 96%, and a specificity of 100%, the calculated VE estimates using both the traditional and test-negative control groups closely approximated the true VE for all values from 30% to 100%. As true VE decreased, the traditional case-control approach slightly overestimated the true VE and the test-negative case-control approach slightly underestimated this estimate, but the absolute difference was only ±0.2 percentage points. Field VE estimates from 10 evaluations that used both traditional and test-negative control groups were similar regardless of control group used. The use of rotavirus test-negative controls offers an efficient and cost-effective approach to estimating rotavirus VE through case-control studies. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  20. Immunoglobulin G antibodies against indoor dampness-related microbes and adult-onset asthma: a population-based incident case–control study

    PubMed Central

    JAAKKOLA, M S; LAITINEN, S; PIIPARI, R; UITTI, J; NORDMAN, H; HAAPALA, A-M; JAAKKOLA, J J K

    2002-01-01

    Immunoglobulin G (IgG) antibodies against microbes related to indoor dampness problems have been used as potential biomarkers of fungal exposure in clinical investigations. There is limited information on their relation to asthma. We conducted a population-based incident case–control study to assess the risk of asthma in relation to specific IgG antibodies to eight dampness-related microbes: Aspergillus fumigatus, A. versicolor, Cladosporium cladosporioides, Fusarium oxysporum, Sporobolomyces salmonicolor, Stachybotrys chartarum, Streptomyces albus and Trichoderma citrinoviride. We recruited systematically all new cases of asthma during a 2·5-year study period and randomly selected controls from a source population of adults 21–63 years of age living in the Pirkanmaa Hospital District, South Finland. The clinically diagnosed case series consisted of 521 adults with newly diagnosed asthma and the control series of 932 controls selected randomly from the source population. IgG antibodies were analysed with ELISA. An increased risk of developing asthma in adulthood was significantly related to IgG antibodies to T. citrinoviride, but not to the other moulds. There was no evidence of a dose–response relation between the IgG antibody level and the risk of asthma. T. citrinoviride may play a role in the aetiology of adult-onset asthma or serve as an indicator of other causal factors. PMID:12100029

  1. Smoking and adult glioma: a population-based case-control study in China.

    PubMed

    Hou, Lei; Jiang, Jingmei; Liu, Boqi; Han, Wei; Wu, Yanping; Zou, Xiaonong; Nasca, Philip C; Xue, Fang; Chen, Yuanli; Zhang, Biao; Pang, Haiyu; Wang, Yuyan; Wang, Zixing; Li, Junyao

    2016-01-01

    Smoking increases the risk of numerous cancers; however, an association of smoking with adult gliomas has not been found in a population. This case-control study included 4556 glioma cases (ICD-9 code 191.0-191.9) aged ≥ 30 years and 9112 controls from a national survey of smoking and mortality in China in 1989-1991. Controls from 325 255 surviving spouses of all-cause deaths were randomly assigned to cases in each of 103 areas according to sex and age groups at a ratio of 2:1. Smoking information was ascertained retrospectively by interviewing surviving spouses. After adjustment for confounders, smoking increased the risk of glioma deaths by 11% (odds ratio [OR] = 1.11; 95% confidence interval [CI]: 1.03-1.21). Compared with non-smokers; the increased risk was 9% (OR = 1.09; 95% CI: 0.99-1.20) in men and 16% (OR = 1.16; 95% CI: 1.00-1.36) in women. The risk increased with age and doses. For individuals aged ≥ 50 years, smoking was associated with higher risk of glioma death by 25% (OR = 1.25; 95% CI: 1.15-1.38); this increased risk for smokers who smoked ≥ 20 cigarettes daily for ≥ 30 years was 53% (OR = 1.53; 95% CI: 1.34-1.74). There were similar findings in both men and women and with either pathology-based or non-pathology-based comparisons. This study indicates that smoking is associated with glioma deaths in the Chinese population. Long-term heavy smoking could be a factor for risk stratification in individuals attending brain tumor clinics. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. High risk of brain tumors in farmers: a mini-review of the literature, and report of the results of a case control study.

    PubMed

    Fallahi, P; Foddis, R; Cristaudo, A; Antonelli, A

    2017-01-01

    Even though a relationship between farmer work and the development of brain tumors was suggest by the scientific literature, a small number of italian studies investigate on the impact of this job on the cancer morbidity of farmer population. The informations about this case-control study were obtained from patients recruited in the Neurosurgical Department of the University-Hospital of Pisa, Italy, from 1990 to 2000. One hundred and seventy-four, newly diagnosed cases of brain tumors (glioma and meningiomas, histologically confirmed), were recruited, such as 522 controls (with other non tumoral neurologic diseases: trauma, etc), by matching cases and controls (1:3), for age (± 5 years) and gender. Cases and controls were interviewed in the Neurosurgical Department, University-Hospital of Pisa, Italy, and the occupational histories of cases and controls were compared. Cases and controls have showed a statistically significant difference, based on their occupation (agricultural vs. non-agricultural). We observed a significant association among brain tumors and rural activity in evaluated patients (P=0.008). Further studies regarding this population group are needed, to determine the causes for the increased risk of this cancer, particularly in regions where there is an intense agricultural activity and where pesticides are used. Furthermore, a subsequent reevaluation in other patients collected in more recent years will be needed to evaluate the trend of this association.

  3. Large-scale replication and heterogeneity in Parkinson disease genetic loci

    PubMed Central

    Ioannidis, John P.A.; Aasly, Jan O.; Annesi, Grazia; Brice, Alexis; Van Broeckhoven, Christine; Bertram, Lars; Bozi, Maria; Crosiers, David; Clarke, Carl; Facheris, Maurizio; Farrer, Matthew; Garraux, Gaetan; Gispert, Suzana; Auburger, Georg; Vilariño-Güell, Carles; Hadjigeorgiou, Georgios M.; Hicks, Andrew A.; Hattori, Nobutaka; Jeon, Beom; Lesage, Suzanne; Lill, Christina M.; Lin, Juei-Jueng; Lynch, Timothy; Lichtner, Peter; Lang, Anthony E.; Mok, Vincent; Jasinska-Myga, Barbara; Mellick, George D.; Morrison, Karen E.; Opala, Grzegorz; Pramstaller, Peter P.; Pichler, Irene; Park, Sung Sup; Quattrone, Aldo; Rogaeva, Ekaterina; Ross, Owen A.; Stefanis, Leonidas; Stockton, Joanne D.; Satake, Wataru; Silburn, Peter A.; Theuns, Jessie; Tan, Eng-King; Toda, Tatsushi; Tomiyama, Hiroyuki; Uitti, Ryan J.; Wirdefeldt, Karin; Wszolek, Zbigniew; Xiromerisiou, Georgia; Yueh, Kuo-Chu; Zhao, Yi; Gasser, Thomas; Maraganore, Demetrius; Krüger, Rejko

    2012-01-01

    Objective: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. Methods: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. Results: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78–0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14–1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I2 estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. Conclusion: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity. Neurology® 2012;79:659–667 PMID:22786590

  4. Large-scale replication and heterogeneity in Parkinson disease genetic loci.

    PubMed

    Sharma, Manu; Ioannidis, John P A; Aasly, Jan O; Annesi, Grazia; Brice, Alexis; Van Broeckhoven, Christine; Bertram, Lars; Bozi, Maria; Crosiers, David; Clarke, Carl; Facheris, Maurizio; Farrer, Matthew; Garraux, Gaetan; Gispert, Suzana; Auburger, Georg; Vilariño-Güell, Carles; Hadjigeorgiou, Georgios M; Hicks, Andrew A; Hattori, Nobutaka; Jeon, Beom; Lesage, Suzanne; Lill, Christina M; Lin, Juei-Jueng; Lynch, Timothy; Lichtner, Peter; Lang, Anthony E; Mok, Vincent; Jasinska-Myga, Barbara; Mellick, George D; Morrison, Karen E; Opala, Grzegorz; Pramstaller, Peter P; Pichler, Irene; Park, Sung Sup; Quattrone, Aldo; Rogaeva, Ekaterina; Ross, Owen A; Stefanis, Leonidas; Stockton, Joanne D; Satake, Wataru; Silburn, Peter A; Theuns, Jessie; Tan, Eng-King; Toda, Tatsushi; Tomiyama, Hiroyuki; Uitti, Ryan J; Wirdefeldt, Karin; Wszolek, Zbigniew; Xiromerisiou, Georgia; Yueh, Kuo-Chu; Zhao, Yi; Gasser, Thomas; Maraganore, Demetrius; Krüger, Rejko

    2012-08-14

    Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown. Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry. In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I(2) estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD. Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity.

  5. Costs of venous thromboembolism associated with hospitalization for medical illness.

    PubMed

    Cohoon, Kevin P; Leibson, Cynthia L; Ransom, Jeanine E; Ashrani, Aneel A; Petterson, Tanya M; Long, Kirsten Hall; Bailey, Kent R; Heit, Johm A

    2015-04-01

    To determine population-based estimates of medical costs attributable to venous thromboembolism (VTE) among patients currently or recently hospitalized for acute medical illness. Population-based cohort study conducted in Olmsted County, Minnesota. Using Rochester Epidemiology Project (REP) resources, we identified all Olmsted County residents with objectively diagnosed incident VTE during or within 92 days of hospitalization for acute medical illness over the 18-year period of 1988 to 2005 (n=286). One Olmsted County resident hospitalized for medical illness without VTE was matched to each case for event date (±1 year), duration of prior medical history, and active cancer status. Subjects were followed forward in REP provider-linked billing data for standardized, inflation-adjusted direct medical costs (excluding outpatient pharmaceutical costs) from 1 year before their respective event or index date to the earliest of death, emigration from Olmsted County, or December 31, 2011 (study end date). We censored follow-up such that each case and matched control had similar periods of observation. We used generalized linear modeling (controlling for age, sex, preexisting conditions, and costs 1 year before index) to predict costs for cases and controls. Adjusted mean predicted costs were 2.5-fold higher for cases ($62,838) than for controls ($24,464) (P<.001) from index to up to 5 years post index. Cost differences between cases and controls were greatest within the first 3 months after the event date (mean difference=$16,897) but costs remained significantly higher for cases compared with controls for up to 3 years. VTE during or after recent hospitalization for medical illness contributes a substantial economic burden.

  6. Statin Use and Fatal Prostate Cancer: A Matched Case-Control Study

    PubMed Central

    Marcella, Stephen W.; David, Alice; Ohman-Strickland, Pamela A.; Carson, Jeffery; Rhoads, George G.

    2015-01-01

    Background Statins are one of the most commonly prescribed medications in medical practice and prostate cancer is the most common male malignancy. While there has been no consistent evidence that statins affect cancer incidence, including prostate cancer, several reports suggest they may decrease the rate of advanced prostate cancer. However, no study has examined statin use and prostate cancer mortality specifically. We report here a population-based case-control investigation that examines this association. Methods We conducted a matched case-control study. Cases were residents of New Jersey ages 55 – 79 who died from prostate cancer between 1997–2000. We individually matched population-based controls by five-year age-group and race. Medication data were obtained identically for cases and controls from blinded medical chart review. We used conditional logistic regression to adjust for confounders. Results We identified 718 cases and obtained cooperation from 77% of their spouses (N=553). After review of medical records, 387 were eligible and 380 were matched to a control. The unadjusted odds ratio was 0.49 (95% CI, 0.34–0.70) which decreased to 0.37 (p<0.0001) after adjustment for education, waist size, BMI, comorbidities, and anti-hypertensive medication. There was little difference between lipophilic and hydrophilic statins but more risk reduction was noted for hi-potency statins (73%, p<0.0001) as compared to low-potency statins (31%, p=0.32). Conclusion Statin use is associated with substantial protection against prostate cancer death, adding to the epidemiologic evidence for an inhibitory effect on prostate cancer. PMID:22180145

  7. IT Governance in SMEs: Trust or Control?

    NASA Astrophysics Data System (ADS)

    Devos, Jan; van Landeghem, Hendrik; Deschoolmeester, Dirk

    It is believed by many scholars that a small and medium-sized enterprise (SME) cannot be seen through the lens of a large firm. Theories which explain IT governance in large organizations and methodologies used by practitioners can therefore not be extrapolated to SMEs, which have a completely different economic, cultural and managerial environment. SMEs suffer from resource poverty, have less IS experience and need more external support. SMEs largely contribute to the failure of many IS projects. We define an outsourced information system failure (OISF) as a failure of IT governance in an SME environment and propose a structure for stating propositions derived from both agency theory and theory of trust. The theoretical question addressed in this paper is: how and why do OISFs occur in SMEs? We have chosen a qualitative and positivistic IS case study research strategy based on multiple cases. Eight cases of IS projects were selected. We found that trust is more important than control issues like output-based contracts and structured controls for eliminating opportunistic behaviour in SMEs. We conclude that the world of SMEs is significantly different from that of large companies. This necessitates extra care to be taken on the part of researchers and practitioners when designing artefacts for SMEs.

  8. Pleural mesothelioma and occupational and non-occupational asbestos exposure: a case-control study with quantitative risk assessment.

    PubMed

    Ferrante, Daniela; Mirabelli, Dario; Tunesi, Sara; Terracini, Benedetto; Magnani, Corrado

    2016-03-01

    Casale Monferrato (north west Italy) is an area with an exceptionally high incidence of mesothelioma caused by asbestos contamination at work and in the general environment from the asbestos-cement Eternit plant that was operational until 1986. The purpose of this study was to quantify the association between pleural malignant mesothelioma (PMM) and asbestos cumulative exposure using individual assessment of environmental and domestic exposure, as well as of occupational exposure. This population-based case-control study included cases of PMM diagnosed between January 2001 and June 2006 among residents in the Casale Monferrato Local Health Authority. Population controls were randomly sampled, matched by age and sex to cases. Cumulative exposure was estimated to account for the lifelong exposure history. Analyses were conducted using unconditional logistic regression models adjusting for gender, age at diagnosis and type of interview (direct or proxy respondents). 200 PMM cases of 223 eligible cases (89.7%) and 348 (63%) of 552 eligible controls accepted to be interviewed. ORs increased with cumulative exposure index (p<0.0001) from 4.4 (CI 95% 1.7 to 11.3) (<1 f/mL-years) to 62.1 (CI 95% 22.2 to 173.2) (≥10 f/mL-years). Among subjects never occupationally exposed, corresponding ORs were 3.8 (CI 95% 1.3 to 11.1) and 23.3 (CI 95% 2.9 to 186.9) (reference: background level of asbestos exposure). ORs of about 2, statistically significant, were observed for domestic exposure and for living in houses near buildings with large asbestos cement parts. Risk of PMM increased with cumulative asbestos exposure and also in analyses limited to subjects non-occupationally exposed. Our results also provide indication of risk associated with common sources of environmental exposure and are highly relevant for the evaluation of residual risk after the cessation of asbestos industrial use. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Effects of Reservoir Characteristics on Malaria and its vector Abundance: A Case Study of the Bongo District of Ghana

    NASA Astrophysics Data System (ADS)

    Ofosu, E.; Awuah, E.; Annor, F. O.

    2009-04-01

    In the seven (7) administrative zones of the Bongo District of the Upper East Region of Ghana, the occurrences of malaria and relative abundance of the principal malaria vector, Anopheles species, were studied as a function of the presence and characteristics of reservoirs during the rainy season. Case studies in the sub-Sahara Africa indicate that malaria transmission may increase decrease or remain largely unchanged as a consequence of reservoir presence. Analysis made, shows that the distance from reservoir to settlement and surface area of reservoirs significantly affected adult Anopheles mosquito abundance. Percentage of inhabitants using insecticide treated nets, livestock population density, human population density and Anopheles mosquito abundance significantly affected the occurrence of malaria. The results suggest that vector control targeted at reservoir characteristics and larval control, and supplemented by high patronage of insecticide treated nets may be an effective approach for epidemic malaria control in the Bongo District. Key Words: Bongo District, Reservoir, Anopheles species, Malaria, Vector abundance.

  10. Childhood hematologic cancer and residential proximity to oil and gas development

    PubMed Central

    McKenzie, Lisa M.; Allshouse, William B.; Byers, Tim E.; Bedrick, Edward J.; Serdar, Berrin; Adgate, John L.

    2017-01-01

    Background Oil and gas development emits known hematological carcinogens, such as benzene, and increasingly occurs in residential areas. We explored whether residential proximity to oil and gas development was associated with risk for hematologic cancers using a registry-based case-control study design. Methods Participants were 0–24 years old, living in rural Colorado, and diagnosed with cancer between 2001–2013. For each child in our study, we calculated inverse distance weighted (IDW) oil and gas well counts within a 16.1-kilometer radius of residence at cancer diagnosis for each year in a 10 year latency period to estimate density of oil and gas development. Logistic regression, adjusted for age, race, gender, income, and elevation was used to estimate associations across IDW well count tertiles for 87 acute lymphocytic leukemia (ALL) cases and 50 non-Hodgkin lymphoma (NHL) cases, compared to 528 controls with non-hematologic cancers. Findings Overall, ALL cases 0–24 years old were more likely to live in the highest IDW well count tertiles compared to controls, but findings differed substantially by age. For ages 5–24, ALL cases were 4.3 times as likely to live in the highest tertile, compared to controls (95% CI: 1.1 to 16), with a monotonic increase in risk across tertiles (trend p-value = 0.035). Further adjustment for year of diagnosis increased the association. No association was found between ALL for children aged 0–4 years or NHL and IDW well counts. While our study benefited from the ability to select cases and controls from the same population, use of cancer-controls, the limited number of ALL and NHL cases, and aggregation of ages into five year ranges, may have biased our associations toward the null. In addition, absence of information on O&G well activities, meteorology, and topography likely reduced temporal and spatial specificity in IDW well counts. Conclusion Because oil and gas development has potential to expose a large population to known hematologic carcinogens, further study is clearly needed to substantiate both our positive and negative findings. Future studies should incorporate information on oil and gas development activities and production levels, as well as levels of specific pollutants of interest (e.g. benzene) near homes, schools, and day care centers; provide age-specific residential histories; compare cases to controls without cancer; and address other potential confounders, and environmental stressors. PMID:28199334

  11. Isohaline position as a habitat indicator for estuarine populations

    USGS Publications Warehouse

    Jassby, Alan D.; Kimmerer, W.J.; Monismith, Stephen G.; Armor, C.; Cloern, James E.; Powell, T.M.; Vedlinski, Timothy J.

    1995-01-01

    The striped bass survival data were also used to illustrate a related important point: incorporating additionalexplanatory variables may decrease the prediction error for a population or process, but it can increase theuncertainty in parameter estimates and management strategies based on these estimates. Even in cases wherethe uncertainty is currently too large to guide management decisions, an uncertainty analysis can identify themost practical direction for future data acquisition.

  12. Measuring local depletion of terrestrial game vertebrates by central-place hunters in rural Amazonia

    PubMed Central

    Peres, Carlos A.; Costa, Hugo C. M.

    2017-01-01

    The degree to which terrestrial vertebrate populations are depleted in tropical forests occupied by human communities has been the subject of an intense polarising debate that has important conservation implications. Conservation ecologists and practitioners are divided over the extent to which community-based subsistence offtake is compatible with ecologically functional populations of tropical forest game species. To quantify depletion envelopes of forest vertebrates around human communities, we deployed a total of 383 camera trap stations and 78 quantitative interviews to survey the peri-community areas controlled by 60 semi-subsistence communities over a combined area of over 3.2 million hectares in the Médio Juruá and Uatumã regions of Central-Western Brazilian Amazonia. Our results largely conform with prior evidence that hunting large-bodied vertebrates reduces wildlife populations near settlements, such that they are only found at a distance to settlements where they are hunted less frequently. Camera trap data suggest that a select few harvest-sensitive species, including lowland tapir, are either repelled or depleted by human communities. Nocturnal and cathemeral species were detected relatively more frequently in disturbed areas close to communities, but individual species did not necessarily shift their activity patterns. Group biomass of all species was depressed in the wider neighbourhood of urban areas rather than communities. Interview data suggest that species traits, especially group size and body mass, mediate these relationships. Large-bodied, large-group-living species are detected farther from communities as reported by experienced informants. Long-established communities in our study regions have not “emptied” the surrounding forest. Low human population density and low hunting offtake due to abundant sources of alternative aquatic protein, suggest that these communities represent a best-case scenario for sustainable hunting of wildlife for food, thereby providing a conservative assessment of game depletion. Given this ‘best-case’ camera trap and interview-based evidence for hunting depletion, regions with higher human population densities, external trade in wildlife and limited access to alternative protein will likely exhibit more severe depletion. PMID:29040340

  13. Association between osteoporosis and urinary calculus: evidence from a population-based study.

    PubMed

    Keller, J J; Lin, C-C; Kang, J-H; Lin, H-C

    2013-02-01

    This population-based case-control analysis investigated the association between osteoporosis and prior urinary calculus (UC) in Taiwan. We succeeded in detecting an association between osteoporosis and prior UC (adjusted odds ratio = 1.66). This association was consistent and significant regardless of stone location. UC has been demonstrated to be a risk factor for osteoporotic fractures, but no studies to date have directly investigated the association between UC and osteoporosis. This case-control analysis aimed to investigate the association of osteoporosis with prior UC using a population-based dataset in Taiwan. We first identified 39,840 cases ≥40 years who received their first-time diagnosis of osteoporosis between 2002 and 2009 and then randomly selected 79,680 controls. We used conditional logistic regression analyses to compute the odds ratio (OR) and the corresponding 95 % confidence interval (CI) for having been previously diagnosed with UC between cases and controls. The OR of having been previously diagnosed with UC for patients with osteoporosis was 1.66 (95 % CI = 1.59-1.73) when compared to controls after adjusting for geographic location, urbanization level, type I diabetes mellitus, coronary heart disease, hyperlipidemia, rheumatoid arthritis, stroke, renal disease, Parkinson's disease, hyperthyroidism, chronic hepatopathy, Cushing's syndrome, malabsorption, gastrectomy, obesity, and alcohol abuse/alcohol dependence syndrome. The results consistently showed that osteoporosis was significantly associated with a previous diagnosis of UC regardless of stone location; the adjusted ORs of prior kidney calculus, ureter calculus, bladder calculus, and unspecified calculus when compared to controls were 1.71 (95 % CI = 1.61-1.81), 1.60 (95 % CI = 1.47-1.74), 1.59 (95 % CI = 1.23-2.04), and 1.69 (95 % CI = 1.59-1.80), respectively. This study succeeded in detecting an association between osteoporosis and prior UC. In addition, our findings were consistent and significant regardless of stone location.

  14. Case-control vaccine effectiveness studies: Preparation, design, and enrollment of cases and controls.

    PubMed

    Verani, Jennifer R; Baqui, Abdullah H; Broome, Claire V; Cherian, Thomas; Cohen, Cheryl; Farrar, Jennifer L; Feikin, Daniel R; Groome, Michelle J; Hajjeh, Rana A; Johnson, Hope L; Madhi, Shabir A; Mulholland, Kim; O'Brien, Katherine L; Parashar, Umesh D; Patel, Manish M; Rodrigues, Laura C; Santosham, Mathuram; Scott, J Anthony; Smith, Peter G; Sommerfelt, Halvor; Tate, Jacqueline E; Victor, J Chris; Whitney, Cynthia G; Zaidi, Anita K; Zell, Elizabeth R

    2017-06-05

    Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide policy-relevant data on vaccine performance under 'real world' conditions, contributing to the evidence base to support and sustain introduction of new vaccines. However, case-control studies do not measure the impact of vaccine introduction on disease at a population level, and are subject to bias and confounding, which may lead to inaccurate results that can misinform policy decisions. In 2012, a group of experts met to review recent experience with case-control studies evaluating the effectiveness of several vaccines; here we summarize the recommendations of that group regarding best practices for planning, design and enrollment of cases and controls. Rigorous planning and preparation should focus on understanding the study context including healthcare-seeking and vaccination practices. Case-control vaccine effectiveness studies are best carried out soon after vaccine introduction because high coverage creates strong potential for confounding. Endpoints specific to the vaccine target are preferable to non-specific clinical syndromes since the proportion of non-specific outcomes preventable through vaccination may vary over time and place, leading to potentially confusing results. Controls should be representative of the source population from which cases arise, and are generally recruited from the community or health facilities where cases are enrolled. Matching of controls to cases for potential confounding factors is commonly used, although should be reserved for a limited number of key variables believed to be linked to both vaccination and disease. Case-control vaccine effectiveness studies can provide information useful to guide policy decisions and vaccine development, however rigorous preparation and design is essential. Published by Elsevier Ltd.

  15. Metformin for primary colorectal cancer prevention in patients with diabetes: a case-control study in a US population.

    PubMed

    Sehdev, Amikar; Shih, Ya-Chen T; Vekhter, Benjamin; Bissonnette, Marc B; Olopade, Olufunmilayo I; Polite, Blase N

    2015-04-01

    Emerging evidence from observational studies has suggested that metformin may be beneficial in the primary prevention of colorectal cancer (CRC). However, to the authors' knowledge, none of these studies was conducted in a US population. Because environmental factors such as Western diet and obesity are implicated in the causation of CRC, a large case-control study was performed to assess the effects of metformin on the incidence of CRC in a US population. MarketScan databases were used to identify diabetic patients with CRC. A case was defined as having an incident diagnosis of CRC. Up to 2 controls matched for age, sex, and geographical region were selected for each case. Metformin exposure was assessed by prescription tracking within the 12-month period before the index date. Conditional logistic regression was used to adjust for multiple potential confounders and to calculate adjusted odds ratios (AORs). The mean age of the study participants was 55 years and 57 years, respectively, in the control and case groups (P = 1.0). Approximately 60% of the study participants were male and 40% were female in each group. In the multivariable model, any metformin use was associated with a 15% reduction in the odds of CRC (AOR, 0.85; 95% confidence interval, 0.76-0.95 [P = .007]). After adjusting for health care use, the beneficial effect of metformin was reduced to 12% (AOR, 0.88; 95% confidence interval, 0.77-1.00 [P = .05]). The dose-response analyses demonstrated no significant association with metformin dose, duration, or total exposure. Metformin use appears to be associated with a reduced risk of developing CRC among diabetic patients in the United States. © 2014 American Cancer Society.

  16. Risk factors for operated carpal tunnel syndrome: a multicenter population-based case-control study

    PubMed Central

    Mattioli, Stefano; Baldasseroni, Alberto; Bovenzi, Massimo; Curti, Stefania; Cooke, Robin MT; Campo, Giuseppe; Barbieri, Pietro G; Ghersi, Rinaldo; Broccoli, Marco; Cancellieri, Maria Pia; Colao, Anna Maria; dell'Omo, Marco; Fateh-Moghadam, Pirous; Franceschini, Flavia; Fucksia, Serenella; Galli, Paolo; Gobba, Fabriziomaria; Lucchini, Roberto; Mandes, Anna; Marras, Teresa; Sgarrella, Carla; Borghesi, Stefano; Fierro, Mauro; Zanardi, Francesca; Mancini, Gianpiero; Violante, Francesco S

    2009-01-01

    Background Carpal tunnel syndrome (CTS) is a socially and economically relevant disease caused by compression or entrapment of the median nerve within the carpal tunnel. This population-based case-control study aims to investigate occupational/non-occupational risk factors for surgically treated CTS. Methods Cases (n = 220) aged 18-65 years were randomly drawn from 13 administrative databases of citizens who were surgically treated with carpal tunnel release during 2001. Controls (n = 356) were randomly sampled from National Health Service registry records and were frequency matched by age-gender-specific CTS hospitalization rates. Results At multivariate analysis, risk factors were blue-collar/housewife status, BMI ≥ 30 kg/m2, sibling history of CTS and coexistence of trigger finger. Being relatively tall (cut-offs based on tertiles: women ≥165 cm; men ≥175 cm) was associated with lower risk. Blue-collar work was a moderate/strong risk factor in both sexes. Raised risks were apparent for combinations of biomechanical risk factors that included frequent repetitivity and sustained force. Conclusion This study strongly underlines the relevance of biomechanical exposures in both non-industrial and industrial work as risk factors for surgically treated CTS. PMID:19758429

  17. Experience with multiple control groups in a large population-based case-control study on genetic and environmental risk factors.

    PubMed

    Pomp, E R; Van Stralen, K J; Le Cessie, S; Vandenbroucke, J P; Rosendaal, F R; Doggen, C J M

    2010-07-01

    We discuss the analytic and practical considerations in a large case-control study that had two control groups; the first control group consisting of partners of patients and the second obtained by random digit dialling (RDD). As an example of the evaluation of a general lifestyle factor, we present body mass index (BMI). Both control groups had lower BMIs than the patients. The distribution in the partner controls was closer to that of the patients, likely due to similar lifestyles. A statistical approach was used to pool the results of both analyses, wherein partners were analyzed with a matched analysis, while RDDs were analyzed without matching. Even with a matched analysis, the odds ratio with partner controls remained closer to unity than with RDD controls, which is probably due to unmeasured confounders in the comparison with the random controls as well as intermediary factors. However, when studying injuries as a risk factor, the odds ratio remained higher with partner control subjects than with RRD control subjects, even after taking the matching into account. Finally we used factor V Leiden as an example of a genetic risk factor. The frequencies of factor V Leiden were identical in both control groups, indicating that for the analyses of this genetic risk factor the two control groups could be combined in a single unmatched analysis. In conclusion, the effect measures with the two control groups were in the same direction, and of the same order of magnitude. Moreover, it was not always the same control group that produced the higher or lower estimates, and a matched analysis did not remedy the differences. Our experience with the intricacies of dealing with two control groups may be useful to others when thinking about an optimal research design or the best statistical approach.

  18. Risk Factors and Predictors for Candidemia in Pediatric Intensive Care Unit Patients: Implications for Prevention

    PubMed Central

    Zaoutis, Theoklis E.; Prasad, Priya A.; Localio, A. Russell; Coffin, Susan E.; Bell, Louis M.; Walsh, Thomas J.; Gross, Robert

    2013-01-01

    Summary Few data exist on risk factors for candidemia in pediatric intensive care unit (PICU) patients who are at high risk of mortality from infection. We conducted a population-based case-control study to determine risk factors and predictors for candidemia in the PICU. Background Candida species are the leading cause of invasive fungal infections in hospitalized children and are the third most common isolates recovered from pediatric healthcare-associated bloodstream infection in the US [1]. Few data exist on risk factors for candidemia in pediatric intensive care unit (PICU) patients. Methods We conducted a population-based case-control study of PICU patients at Children's Hospital of Philadelphia (CHOP) from 1997-2004. Cases were identified using laboratory records, controls were selected from PICU rosters. Controls were matched to cases by incidence density sampling, adjusting for time at risk. Following conditional multivariate analysis, we performed weighted multivariate analysis to determine predicted probabilities for candidemia given certain risk factor combinations. Results We identified 101 cases of candidemia(incidence,3.5/1,000 PICU admissions). Factors independently associated with candidemia included presence of a central venous catheter(OR 30.4;CI,7.7,119.5), malignancy(OR 4.0;CI,1.23,13.1), use of vancomycin for >3 days in the prior two weeks(OR 6.2;CI,2.4,16), and receipt of agents with activity against anaerobic organisms for >3 days in the prior two weeks(OR 3.5;CI, 1.5,8.4). Predicted probability of various combinations of the factors above ranged from 10.7%-46%. The 30-day mortality rate was 44% in cases compared to 14% in controls (OR 4.22;CI,2.35,7.60). Conclusions To our knowledge, this is the first study to evaluate independent risk factors and to determine a population of children in PICUs at high risk for developing candidemia. Future efforts should focus on validation of these risk factors identified in a different PICU population and development of interventions for prevention of candidemia in critically ill children. PMID:20636126

  19. A prevalence-based association test for case-control studies.

    PubMed

    Ryckman, Kelli K; Jiang, Lan; Li, Chun; Bartlett, Jacquelaine; Haines, Jonathan L; Williams, Scott M

    2008-11-01

    Genetic association is often determined in case-control studies by the differential distribution of alleles or genotypes. Recent work has demonstrated that association can also be assessed by deviations from the expected distributions of alleles or genotypes. Specifically, multiple methods motivated by the principles of Hardy-Weinberg equilibrium (HWE) have been developed. However, these methods do not take into account many of the assumptions of HWE. Therefore, we have developed a prevalence-based association test (PRAT) as an alternative method for detecting association in case-control studies. This method, also motivated by the principles of HWE, uses an estimated population allele frequency to generate expected genotype frequencies instead of using the case and control frequencies separately. Our method often has greater power, under a wide variety of genetic models, to detect association than genotypic, allelic or Cochran-Armitage trend association tests. Therefore, we propose PRAT as a powerful alternative method of testing for association.

  20. Awareness and uptake of direct-to-consumer genetic testing among cancer cases, their relatives, and controls: the Northwest Cancer Genetics Network.

    PubMed

    Hall, Taryn O; Renz, Anne D; Snapinn, Katherine W; Bowen, Deborah J; Edwards, Karen L

    2012-07-01

    To determine if awareness of, interest in, and use of direct-to-consumer (DTC) genetic testing is greater in a sample of high-risk individuals (cancer cases and their relatives), compared to controls. Participants were recruited from the Northwest Cancer Genetics Network. A follow-up survey was mailed to participants to assess DTC genetic testing awareness, interest, and use. One thousand two hundred sixty-seven participants responded to the survey. Forty-nine percent of respondents were aware of DTC genetic testing. Of those aware, 19% indicated interest in obtaining and <1% reported having used DTC genetic testing. Additional information supplied by respondents who reported use of DTC genetic tests indicated that 55% of these respondents likely engaged in clinical genetic testing, rather than DTC genetic testing. Awareness of DTC genetic testing was greater in our sample of high-risk individuals than in controls and population-based studies. Although interest in and use of these tests among cases in our sample were equivalent to other population-based studies, interest in testing was higher among relatives and people who self-referred for a registry focused on cancer than among cases and controls. Additionally, our results suggest that there may be some confusion about what constitutes DTC genetic testing.

  1. Association between cervical screening and prevention of invasive cervical cancer in Ontario: a population-based case-control study.

    PubMed

    Vicus, Danielle; Sutradhar, Rinku; Lu, Yan; Kupets, Rachel; Paszat, Lawrence

    2015-01-01

    The aim of this study was to estimate the effect of cervical screening in the prevention of invasive cervical cancer among age groups, using a population-based case-control study in the province of Ontario, Canada. Exposure was defined as cervical cytology history greater than 3 months before the diagnosis date of cervical cancer (index date). Cases were women who were diagnosed with cervical cancer between January 1, 1998, and December 31, 2008. Controls were women without a diagnosis of cervical cancer on, or before, December 31, 2008. Two controls were matched to each case on year of birth and income quintile, as of the index date. Conditional logistic regression was used to estimate the odds ratio for having been screened among those with cervical cancer. Cervical cancer screening performed between 3 and 36 months before the index date was protective against invasive cervical cancer in women aged 40 through 69 years. In women younger than 40 years, cervical cancer screening performed 3 to 36 months before the index date was not protective. Cervical screening is associated with a reduced risk for invasive cervical cancer among women older than 40 years. Cervical cancer resources should be focused on maximizing the risk reduction.

  2. Internet-based control recruitment for a case-control study of major risk factors for stroke in Korea: lessons from the experience.

    PubMed

    Park, Jong-Moo; Cho, Yong-Jin; Lee, Kyung Bok; Park, Tai Hwan; Lee, Soo Joo; Han, Moon-Ku; Ko, Youngchai; Lee, Jun; Cha, Jae-Kwan; Lee, Byung-Chul; Yu, Kyung-Ho; Oh, Mi-Sun; Lee, Ji Sung; Lee, Juneyoung; Bae, Hee-Joon

    2014-01-01

    This study aimed to estimate the population-attributable risks (PARs) of 9 major risk factors for stroke in Korea through a case-control study and to test the feasibility and validity of internet-based control recruitment. From April 2008 to September 2009, controls were enrolled via internet after providing consent for participation through a web-based survey. The cases included patients who were admitted to the participating centers due to acute stroke or transient ischemic attack within 7 days of onset during the study period. Each control was age- and sex-matched with 2 cases. Adjusted odd ratios, age-standardized prevalence, and PARs were estimated for the 9 major risk factors using the prevalence of risk factors in the control group and the age and sex characteristics from Korea's national census data. In total, 1041 controls were matched to 2082 stroke cases. Because of a shortage of elderly controls in the internet-based recruitment, 248 controls were recruited off-line. The PARs were 23.44%, 10.95%, 51.32%, and 6.35% for hypertension, diabetes, smoking, and stroke history, respectively. Hypercholesterolemia, atrial fibrillation, obesity, coronary heart disease, and a family history of stroke were not associated with stroke. Comparison with education and religion of the control group with that mentioned in the national census data showed a notable difference. The study results imply that internet-based control recruitment for a case-control study requires careful selection of risk factors with high self-awareness and effective strategies to facilitate the recruitment of elderly participants. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  3. Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions

    PubMed Central

    Han, Ying; Hazelett, Dennis J.; Wiklund, Fredrik; Schumacher, Fredrick R.; Stram, Daniel O.; Berndt, Sonja I.; Wang, Zhaoming; Rand, Kristin A.; Hoover, Robert N.; Machiela, Mitchell J.; Yeager, Merideth; Burdette, Laurie; Chung, Charles C.; Hutchinson, Amy; Yu, Kai; Xu, Jianfeng; Travis, Ruth C.; Key, Timothy J.; Siddiq, Afshan; Canzian, Federico; Takahashi, Atsushi; Kubo, Michiaki; Stanford, Janet L.; Kolb, Suzanne; Gapstur, Susan M.; Diver, W. Ryan; Stevens, Victoria L.; Strom, Sara S.; Pettaway, Curtis A.; Al Olama, Ali Amin; Kote-Jarai, Zsofia; Eeles, Rosalind A.; Yeboah, Edward D.; Tettey, Yao; Biritwum, Richard B.; Adjei, Andrew A.; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P.; Isaacs, William B.; Chen, Constance; Lindstrom, Sara; Le Marchand, Loic; Giovannucci, Edward L.; Pomerantz, Mark; Long, Henry; Li, Fugen; Ma, Jing; Stampfer, Meir; John, Esther M.; Ingles, Sue A.; Kittles, Rick A.; Murphy, Adam B.; Blot, William J.; Signorello, Lisa B.; Zheng, Wei; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Nemesure, Barbara; Carpten, John; Leske, M. Cristina; Wu, Suh-Yuh; Hennis, Anselm J. M.; Rybicki, Benjamin A.; Neslund-Dudas, Christine; Hsing, Ann W.; Chu, Lisa; Goodman, Phyllis J.; Klein, Eric A.; Zheng, S. Lilly; Witte, John S.; Casey, Graham; Riboli, Elio; Li, Qiyuan; Freedman, Matthew L.; Hunter, David J.; Gronberg, Henrik; Cook, Michael B.; Nakagawa, Hidewaki; Kraft, Peter; Chanock, Stephen J.; Easton, Douglas F.; Henderson, Brian E.; Coetzee, Gerhard A.; Conti, David V.; Haiman, Christopher A.

    2015-01-01

    Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry. Markers at 55 regions passed a region-specific significance threshold (P-value cutoff range: 3.9 × 10−4–5.6 × 10−3) and in 30 regions we identified markers that were more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (P < 5.0 × 10−6) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with P-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation. PMID:26162851

  4. Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions.

    PubMed

    Han, Ying; Hazelett, Dennis J; Wiklund, Fredrik; Schumacher, Fredrick R; Stram, Daniel O; Berndt, Sonja I; Wang, Zhaoming; Rand, Kristin A; Hoover, Robert N; Machiela, Mitchell J; Yeager, Merideth; Burdette, Laurie; Chung, Charles C; Hutchinson, Amy; Yu, Kai; Xu, Jianfeng; Travis, Ruth C; Key, Timothy J; Siddiq, Afshan; Canzian, Federico; Takahashi, Atsushi; Kubo, Michiaki; Stanford, Janet L; Kolb, Suzanne; Gapstur, Susan M; Diver, W Ryan; Stevens, Victoria L; Strom, Sara S; Pettaway, Curtis A; Al Olama, Ali Amin; Kote-Jarai, Zsofia; Eeles, Rosalind A; Yeboah, Edward D; Tettey, Yao; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Chokkalingam, Anand P; Isaacs, William B; Chen, Constance; Lindstrom, Sara; Le Marchand, Loic; Giovannucci, Edward L; Pomerantz, Mark; Long, Henry; Li, Fugen; Ma, Jing; Stampfer, Meir; John, Esther M; Ingles, Sue A; Kittles, Rick A; Murphy, Adam B; Blot, William J; Signorello, Lisa B; Zheng, Wei; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Nemesure, Barbara; Carpten, John; Leske, M Cristina; Wu, Suh-Yuh; Hennis, Anselm J M; Rybicki, Benjamin A; Neslund-Dudas, Christine; Hsing, Ann W; Chu, Lisa; Goodman, Phyllis J; Klein, Eric A; Zheng, S Lilly; Witte, John S; Casey, Graham; Riboli, Elio; Li, Qiyuan; Freedman, Matthew L; Hunter, David J; Gronberg, Henrik; Cook, Michael B; Nakagawa, Hidewaki; Kraft, Peter; Chanock, Stephen J; Easton, Douglas F; Henderson, Brian E; Coetzee, Gerhard A; Conti, David V; Haiman, Christopher A

    2015-10-01

    Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry. Markers at 55 regions passed a region-specific significance threshold (P-value cutoff range: 3.9 × 10(-4)-5.6 × 10(-3)) and in 30 regions we identified markers that were more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (P < 5.0 × 10(-6)) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with P-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Direct medical costs of constipation from childhood to early adulthood: a population-based birth cohort study.

    PubMed

    Choung, Rok Seon; Shah, Nilay D; Chitkara, Denesh; Branda, Megan E; Van Tilburg, Miranda A; Whitehead, William E; Katusic, Slavica K; Locke, G Richard; Talley, Nicholas J

    2011-01-01

    Although direct medical costs for constipation-related medical visits are thought to be high, to date there have been no studies examining whether longitudinal resource use is persistently elevated in children with constipation. Our aim was to estimate the incremental direct medical costs and types of health care use associated with constipation from childhood to early adulthood. A nested case-control study was conducted to evaluate the incremental costs associated with constipation. The original sample consisted of 5718 children in a population-based birth cohort who were born during 1976 to 1982 in Rochester, MN. The cases included individuals who presented to medical facilities with constipation. The controls were matched and randomly selected among all noncases in the sample. Direct medical costs for cases and controls were collected from the time subjects were between 5 and 18 years of age or until the subject emigrated from the community. We identified 250 cases with a diagnosis of constipation in the birth cohort. Although the mean inpatient costs for cases were $9994 (95% Confidence interval [CI] 2538-37,201) compared with $2391 (95% CI 923-7452) for controls (P = 0.22) during the time period, the mean outpatient costs for cases were $13,927 (95% CI 11,325-16,525) compared with $3448 (95% CI 3771-4621) for controls (P < 0.001) during the same time period. The mean annual number of emergency department visits for cases was 0.66 (95% CI 0.62-0.70) compared with 0.34 (95% CI 0.32-0.35) for controls (P < 0.0001). Individuals with constipation have higher medical care use. Outpatient costs and emergency department use were significantly greater for individuals with constipation from childhood to early adulthood.

  6. Statin use and fatal prostate cancer: a matched case-control study.

    PubMed

    Marcella, Stephen W; David, Alice; Ohman-Strickland, Pamela A; Carson, Jeffery; Rhoads, George G

    2012-08-15

    Statins are some of the most commonly prescribed medications in medical practice, and prostate cancer is the most common malignancy among men. Although there has been no consistent evidence that statins affect cancer incidence, including prostate cancer, several reports suggest they may decrease the rate of advanced prostate cancer. However, no study to date has specifically examined statin use and prostate cancer mortality. The authors conducted this population-based case-control investigation to examine this association. This was a matched case-control study. Cases were residents of New Jersey ages 55 to 79 years who died from prostate cancer between 1997 and 2000. The cases were matched individually to population-based controls by 5-year age group and race. Medication data were obtained identically for cases and controls from blinded medical chart review. Conditional logistic regression was used to adjust for confounders. In total, 718 cases were identified, and cooperation was obtained from 77% of their spouses (N = 553). After a review of medical records, 387 men were eligible, and 380 were matched to a control. The unadjusted odds ratio was 0.49 (95% confidence interval, 0.34-0.70) and decreased to 0.37 (P < .0001) after adjusting for education, waist size, body mass index, comorbidities, and antihypertensive medication. There was little difference between lipophilic and hydrophilic statins, but more risk reduction was noted for high-potency statins (73%; P < .0001) compared with low-potency statins (31%; P = .32). Statin use was associated with substantial protection against prostate cancer death, adding to the epidemiologic evidence for an inhibitory effect on prostate cancer. Copyright © 2011 American Cancer Society.

  7. Most Common SNPs Associated with Rheumatoid Arthritis in Subjects of European Ancestry Confer Risk of Rheumatoid Arthritis in African-Americans

    PubMed Central

    Hughes, Laura B.; Reynolds, Richard J.; Brown, Elizabeth E.; Kelley, James M.; Thomson, Brian; Conn, Doyt L.; Jonas, Beth L.; Westfall, Andrew O.; Padilla, Miguel A.; Callahan, Leigh F.; Smith, Edwin A.; Brasington, Richard D.; Edberg, Jeffrey C.; Kimberly, Robert P.; Moreland, Larry W.; Plenge, Robert M.; Bridges, S. Louis

    2010-01-01

    Objective Large-scale genetic association studies have identified over 20 rheumatoid arthritis (RA) risk alleles among individuals of European ancestry. The influence of these risk alleles has not been comprehensively studied in African-Americans. We therefore sought to examine whether these validated RA risk alleles are associated with RA in an African-American population. Methods 27 candidate SNPs were genotyped in 556 autoantibody-positive African-Americans with RA and 791 healthy African-American controls. Odds ratios (OR) and 95% confidence intervals (CI) for each SNP were compared to previously published ORs of RA patients of European ancestry. We then calculated a composite Genetic Risk Score (GRS) for each individual based on the sum of all risk alleles. Results There was overlap in the OR and 95% CI between the European and African-American populations in 24 of the 27 candidate SNPs. Conversely, 3 of the 27 SNPs (CCR6 rs3093023, TAGAP rs394581, TNFAIP3 rs6920220) demonstrated an OR in the opposite direction from those reported in RA patients of European ancestry. The GRS analysis indicated a small but highly significant probability that African-American cases were enriched for the European RA risk alleles relative to controls (p=0.00005). Conclusion The majority of RA risk alleles previously validated among European ancestry RA patients showed similar ORs in our population of African-Americans with RA. Furthermore, the aggregate GRS supports the hypothesis that these SNPs are risk alleles for RA in the African-American population. Future large-scale genetic studies are needed to validate these risk alleles and identify novel risk alleles for RA in African-Americans. PMID:21120996

  8. Rethinking sources of representative controls for the conduct of case-control studies in minority populations.

    PubMed

    Bandera, Elisa V; Chandran, Urmila; Zirpoli, Gary; McCann, Susan E; Ciupak, Gregory; Ambrosone, Christine B

    2013-05-31

    Recruitment of controls remains a challenge in case-control studies and particularly in studies involving minority populations. We compared characteristics of controls recruited through random digit dialing (RDD) to those of community controls enrolled through churches, health events and other outreach sources among women of African ancestry (AA) participating in the Women's Circle of Health Study, a case-control study of breast cancer. Odds ratios and 95% confidence intervals were also computed using unconditional logistic regression to evaluate the impact of including the community controls for selected variables relevant to breast cancer and for which there were significant differences in distribution between the two control groups. Compared to community controls (n=347), RDD controls (n=207) had more years of education and higher income, lower body mass index, were more likely to have private insurance, and less likely to be single. While the percentage of nulliparous women in the two groups was similar, community controls tended to have more children, have their first child at a younger age, and were less likely to breastfeed their children. Dietary intake was similar in the two groups. Compared to census data, the combination of RDD and community controls seems to be more representative of the general population than RDD controls alone. Furthermore, the inclusion of the community group had little impact on the magnitude of risk estimates for most variables, while enhancing statistical power. Community-based recruitment was found to be an efficient and feasible method to recruit AA controls.

  9. Antidepressant Use After Aneurysmal Subarachnoid Hemorrhage: A Population-Based Case-Control Study.

    PubMed

    Huttunen, Jukka; Lindgren, Antti; Kurki, Mitja I; Huttunen, Terhi; Frösen, Juhana; von Und Zu Fraunberg, Mikael; Koivisto, Timo; Kälviäinen, Reetta; Räikkönen, Katri; Viinamäki, Heimo; Jääskeläinen, Juha E; Immonen, Arto

    2016-09-01

    To elucidate the predictors of antidepressant use after subarachnoid hemorrhage from saccular intracranial aneurysm (sIA-SAH) in a population-based cohort with matched controls. The Kuopio sIA database includes all unruptured and ruptured sIA cases admitted to the Kuopio University Hospital from its defined catchment population in Eastern Finland, with 3 matched controls for each patient. The use of all prescribed medicines has been fused from the Finnish national registry of prescribed medicines. In the present study, 2 or more purchases of antidepressant medication indicated antidepressant use. The risk factors of the antidepressant use were analyzed in 940 patients alive 12 months after sIA-SAH, and the classification tree analysis was used to create a predicting model for antidepressant use after sIA-SAH. The 940 12-month survivors of sIA-SAH had significantly more antidepressant use (odds ratio, 2.6; 95% confidence interval, 2.2-3.1) than their 2676 matched controls (29% versus 14%). Classification tree analysis, based on independent risk factors, was used for the best prediction model of antidepressant use after sIA-SAH. Modified Rankin Scale until 12 months was the most potent predictor, followed by condition (Hunt and Hess Scale) and age on admission for sIA-SAH. The sIA-SAH survivors use significantly more often antidepressants, indicative of depression, than their matched population controls. Even with a seemingly good recovery (modified Rankin Scale score, 0) at 12 months after sIA-SAH, there is a significant risk of depression requiring antidepressant medication. © 2016 American Heart Association, Inc.

  10. The behavior of multiple independent managers and ecological traits interact to determine prevalence of weeds.

    PubMed

    Coutts, Shaun R; Yokomizo, Hiroyuki; Buckley, Yvonne M

    2013-04-01

    Management of damaging invasive plants is often undertaken by multiple decision makers, each managing only a small part of the invader's population. As weeds can move between properties and re-infest eradicated sites from unmanaged sources, the dynamics of multiple decision makers plays a significant role in weed prevalence and invasion risk at the landscape scale. We used a spatially explicit agent-based simulation to determine how individual agent behavior, in concert with weed population ecology, determined weed prevalence. We compared two invasive grass species that differ in ecology, control methods, and costs: Nassella trichotoma (serrated tussock) and Eragrostis curvula (African love grass). The way decision makers reacted to the benefit of management had a large effect on the extent of a weed. If benefits of weed control outweighed the costs, and either net benefit was very large or all agents were very sensitive to net benefits, then agents tended to act synchronously, reducing the pool of infested agents available to spread the weed. As N. trichotoma was more damaging than E. curvula and had more effective control methods, agents chose to manage it more often, which resulted in lower prevalence of N. trichotoma. A relatively low number of agents who were intrinsically less motivated to control weeds led to increased prevalence of both species. This was particularly apparent when long-distance dispersal meant each infested agent increased the invasion risk for a large portion of the landscape. In this case, a small proportion of land mangers reluctant to control, regardless of costs and benefits, could lead to the whole landscape being infested, even when local control stopped new infestations. Social pressure was important, but only if it was independent of weed prevalence, suggesting that early access to information, and incentives to act on that information, may be crucial in stopping a weed from infesting large areas. The response of our model to both behavioral and ecological parameters was highly nonlinear. This implies that the outcomes of weed management programs that deal with multiple land mangers could be highly variable in both space and through time.

  11. 77 FR 11136 - Proposed Collection; Comment Request; a Multi-Center International Hospital-Based Case-Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-24

    ... of the world. The contribution of environmental, occupational, and genetic factors to the cause of... loci in Western populations. To optimize the ability to build on and clarify these findings, it is necessary to investigate populations that differ from those in the West in both exposure patterns and...

  12. Multidrug-resistant tuberculosis.

    PubMed

    Zager, Ellen M; McNerney, Ruth

    2008-01-25

    With almost 9 million new cases each year, tuberculosis remains one of the most feared diseases on the planet. Led by the STOP-TB Partnership and WHO, recent efforts to combat the disease have made considerable progress in a number of countries. However, the emergence of mutated strains of Mycobacterium tuberculosis that are resistant to the major anti-tuberculosis drugs poses a deadly threat to control efforts. Multidrug-resistant tuberculosis (MDR-TB) has been reported in all regions of the world. More recently, extensively drug resistant-tuberculosis (XDR-TB) that is also resistant to second line drugs has emerged in a number of countries. To ensure that adequate resources are allocated to prevent the emergence and spread of drug resistance it is important to understand the scale of the problem. In this article we propose that current methods of describing the epidemiology of drug resistant tuberculosis are not adequate for this purpose and argue for the inclusion of population based statistics in global surveillance data. Whereas the prevalence of tuberculosis is presented as the proportion of individuals within a defined population having disease, the prevalence of drug resistant tuberculosis is usually presented as the proportion of tuberculosis cases exhibiting resistance to anti-tuberculosis drugs. Global surveillance activities have identified countries in Eastern Europe, the former Soviet Union and regions of China as having a high proportion of MDR-TB cases and international commentary has focused primarily on the urgent need to improve control in these settings. Other regions, such as sub-Saharan Africa have been observed as having a low proportion of drug resistant cases. However, if one considers the incidence of new tuberculosis cases with drug resistant disease in terms of the population then countries of sub-Saharan Africa have amongst the highest rates of transmitted MDR-TB in the world. We propose that inclusion of population based statistics in global surveillance data is necessary to better inform debate on the control of drug resistant tuberculosis. Re-appraisal of global MDR-TB data to include population based statistics suggests that the problem of drug resistant tuberculosis in sub-Saharan Africa is more critical than previously perceived.

  13. The use of customised versus population-based birthweight standards in predicting perinatal mortality.

    PubMed

    Zhang, X; Platt, R W; Cnattingius, S; Joseph, K S; Kramer, M S

    2007-04-01

    The objective of this study was to critically examine potential artifacts and biases underlying the use of 'customised' standards of birthweight for gestational age (GA). Population-based cohort study. Sweden. A total of 782,303 singletons > or =28 weeks of gestation born in 1992-2001 to Nordic mothers with complete data on birthweight; GA; and maternal age, parity, height, and pre-pregnancy weight. We compared perinatal mortality in four groups of infants based on the following classification of small for gestational age (SGA): non-SGA based on either population-based or customised standards (the reference group), SGA based on the population-based standard only, SGA based on the customised standard only, and SGA according to both standards. We used graphical methods to compare GA-specific birthweight cutoffs for SGA using the two standards and also used logistic regression to control for differences in GA and maternal pre-pregnancy body mass index (BMI) in the four groups. Perinatal mortality, including stillbirth and neonatal death. Customisation led to a large artifactual increase in the proportion of SGA infants born preterm. Adjustment for differences in GA and maternal BMI markedly reduced the excess risk among infants classified as SGA by customised standards only. The large increase in perinatal mortality risk among infants classified as SGA based on customised standards is largely an artifact due to inclusion of more preterm births.

  14. Similarity between generic and brand-name antihypertensive drugs for primary prevention of cardiovascular disease: evidence from a large population-based study.

    PubMed

    Corrao, Giovanni; Soranna, Davide; Merlino, Luca; Mancia, Giuseppe

    2014-10-01

    Although generic and earlier brand-name counterparts are bioequivalent, their equivalence in preventing relevant clinical outcomes is of concern. To compare effectiveness of generic and brand-name antihypertensive drugs for preventing the onset of cardiovascular (CV) outcomes. A population-based, nested case-control study was carried out by including the cohort of 78 520 patients from Lombardy (Italy) aged 18 years or older who were newly treated with antihypertensive drugs during 2005. Cases were the 2206 patients who experienced a hospitalization for CV disease from initial prescription until 2011. One control for each case was randomly selected from the same cohort that generated cases. Logistic regression was used to model the CV risk associated with starting on and/or continuing with generic or brand-name agents. There was no evidence that patients who started on generics experienced different CV risk than those on brand-name product (OR 0·86; 95% CI 0·63-1·17). Patients at whom generics were main dispensed had not significantly difference in CV outcomes than those mainly on brand-name agents (OR 1·19; 95% CI 0·86-1·63). Compared with patients who kept initial brand-name therapy, those who experienced brand-to-generic or generic-to-brand switches, and those always on generics, did not show differential CV risks, being the corresponding ORs (and 95% CIs), 1·18 (0·96-1·47), 0·87 (0·63-1·21) and 1·08 (0·80-1·46). Our findings do not support the notion that brand-name antihypertensive agents are superior to generics for preventing CV outcomes in the real-world clinical practice. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

  15. Stressful psychosocial factors and symptoms of gastroesophageal reflux disease: a population-based study in Norway.

    PubMed

    Jansson, Catarina; Wallander, Mari-Ann; Johansson, Saga; Johnsen, Roar; Hveem, Kristian

    2010-01-01

    Adverse psychosocial factors, including work-related stress, are, like gastroesophageal reflux disease (GERD), increasing health problems in industrialized countries. The importance of clarifying the relation between psychosocial factors and GERD has been stressed, but there are few population-based studies. This was a population-based, cross-sectional, case-control study based on two health surveys conducted in the Norwegian county Nord-Trondelag in 1984-86 and 1995-97. GERD symptoms were assessed in the second survey, which included 65,333 participants, representing 70% of the county's adult population. The 3153 persons reporting severe GERD symptoms were defined as cases and the 40,210 persons without such symptoms were defined as controls. Data on psychosocial factors and potential confounders were collected using questionnaires. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using unconditional logistic regression. In models adjusted for age, sex, smoking, obesity and socioeconomic status, positive associations were observed between high job demands (OR 1.9, 95% CI 1.6-2.2), low job control (OR 1.1, 95% CI 1.0-1.2) and job strain (OR 1.9, 95% CI 1.6-2.4) and risk of GERD symptoms. Persons reporting low job satisfaction had a twofold (95% CI 1.6-2.5) increased risk of GERD compared to persons reporting high job satisfaction. Self pressure (OR 1.8, 95% CI 1.6-2.1) and time pressure (OR 2.0, 95% CI 1.7-2.4) were positively associated with GERD symptoms. These associations were attenuated after further adjustment for anxiety, depression, myocardial infarction, angina pectoris, stroke and insomnia, but remained statistically significant. This population-based study reveals a link between stressful psychosocial factors, including job strain, and GERD symptoms.

  16. Use of Organic Nitrates and the Risk of Hip Fracture: A Population-Based Case-Control Study

    PubMed Central

    Pouwels, Sander; Lalmohamed, Arief; van Staa, Tjeerd; Cooper, Cyrus; Souverein, Patrick; Leufkens, Hubertus G.; Rejnmark, Lars; de Boer, Anthonius; Vestergaard, Peter; de Vries, Frank

    2010-01-01

    Context: Use of organic nitrates has been associated with increased bone mineral density. Moreover, a large Danish case-control study reported a decreased fracture risk. However, the association with duration of nitrate use, dose frequency, and impact of discontinuation has not been extensively studied. Objective: Our objective was to evaluate the association between organic nitrates and hip fracture risk. Methods: A case-control study was conducted using the Dutch PHARMO Record Linkage System (1991–2002, n = 6,763 hip fracture cases and 26,341 controls). Cases had their first admission for hip fracture, whereas controls had not sustained any fracture after enrollment. Current users of organic nitrates were patients who had received a prescription within 90 d before the index date. The analyses were adjusted for disease and drug history. Results: Current use of nitrates was not associated with a decreased risk of hip fracture [adjusted odds ratio (OR) = 0.93; 95% confidence interval (CI) = 0.83–1.04]. Those who used as-needed medication only had a lower risk of hip fracture (adjusted OR = 0.83; 95% CI = 0.63–1.08) compared with users of maintenance medication only (adjusted OR = 1.17; 95% CI = 0.97–1.40). No association was found between duration of nitrate use and fracture risk. Conclusions: Our overall analyses showed that risk of a hip fracture was significantly lower among users of as-needed organic nitrates, when compared with users of maintenance medication. Our analyses of hip fracture risks with duration of use did not further support a beneficial effect of organic nitrates on hip fracture, although residual confounding may have masked beneficial effects. PMID:20130070

  17. Use of organic nitrates and the risk of hip fracture: a population-based case-control study.

    PubMed

    Pouwels, Sander; Lalmohamed, Arief; van Staa, Tjeerd; Cooper, Cyrus; Souverein, Patrick; Leufkens, Hubertus G; Rejnmark, Lars; de Boer, Anthonius; Vestergaard, Peter; de Vries, Frank

    2010-04-01

    Use of organic nitrates has been associated with increased bone mineral density. Moreover, a large Danish case-control study reported a decreased fracture risk. However, the association with duration of nitrate use, dose frequency, and impact of discontinuation has not been extensively studied. Our objective was to evaluate the association between organic nitrates and hip fracture risk. A case-control study was conducted using the Dutch PHARMO Record Linkage System (1991-2002, n = 6,763 hip fracture cases and 26,341 controls). Cases had their first admission for hip fracture, whereas controls had not sustained any fracture after enrollment. Current users of organic nitrates were patients who had received a prescription within 90 d before the index date. The analyses were adjusted for disease and drug history. Current use of nitrates was not associated with a decreased risk of hip fracture [adjusted odds ratio (OR) = 0.93; 95% confidence interval (CI) = 0.83-1.04]. Those who used as-needed medication only had a lower risk of hip fracture (adjusted OR = 0.83; 95% CI = 0.63-1.08) compared with users of maintenance medication only (adjusted OR = 1.17; 95% CI = 0.97-1.40). No association was found between duration of nitrate use and fracture risk. Our overall analyses showed that risk of a hip fracture was significantly lower among users of as-needed organic nitrates, when compared with users of maintenance medication. Our analyses of hip fracture risks with duration of use did not further support a beneficial effect of organic nitrates on hip fracture, although residual confounding may have masked beneficial effects.

  18. The case for improving road safety in Pacific Islands: a population-based study from Fiji (TRIP 6).

    PubMed

    Herman, Josephine; Ameratunga, Shanthi; Wainiqolo, Iris; Kafoa, Berlin; McCaig, Eddie; Jackson, Rod

    2012-10-01

    To estimate the incidence and demographic characteristics associated with road traffic injuries (RTIs) resulting in deaths or hospital admission for 12 hours or more in Viti Levu, Fiji. Analysis of the prospective population-based Fiji Injury Surveillance in Hospitals database (October 2005 - September 2006). Of the 374 RTI cases identified (17% of all injuries), 72% were males and one third were aged 15-29 years. RTI fatalities (10.3 per 100,000 per year) were higher among Indians compared to Fijians. Two-thirds of deaths (largely ascribed to head, chest and abdominal trauma) occurred before hospital admission. While the RTI fatality rate was comparable to the global average for high-income countries, the level of motorisation in Fiji is considerably lower. To avert rising RTI rates with increasing motorisation, Fiji requires a robust road safety strategy alongside effective trauma-care services and a reliable population-based RTI surveillance system. © 2012 The Authors. ANZJPH © 2012 Public Health Association of Australia.

  19. Non-specific effect of measles vaccination on overall child mortality in an area of rural India with high vaccination coverage: a population-based case-control study.

    PubMed Central

    Kabir, Zubair; Long, Jean; Reddaiah, Vankadara P.; Kevany, John; Kapoor, Suresh K.

    2003-01-01

    OBJECTIVE: To determine whether vaccination against measles in a population with sustained high vaccination coverage and relatively low child mortality reduces overall child mortality. METHODS: In April and May 2000, a population-based, case-control study was conducted at Ballabgarh (an area in rural northern India). Eligible cases were 330 children born between 1 January 1991 and 31 December 1998 who died aged 12-59 months. A programme was used to match 320 controls for age, sex, family size, and area of residence from a birth cohort of 15 578 born during the same time period. FINDINGS: The analysis used 318 matched pairs and suggested that children aged 12-59 months who did not receive measles vaccination in infancy were three times more likely to die than those vaccinated against measles. Children from lower caste households who were not vaccinated in infancy had the highest risk of mortality (odds ratio, 8.9). A 27% increase in child mortality was attributable to failure to vaccinate against measles in the study population. CONCLUSION: Measles vaccine seems to have a non-specific reducing effect on overall child mortality in this population. If true, children in lower castes may reap the greatest gains in survival. The findings should be interpreted with caution because the nutritional status of the children was not recorded and may be a residual confounder. "All-cause mortality" is a potentially useful epidemiological endpoint for future vaccine trials. PMID:12764490

  20. Poor oral health is associated with an increased risk of esophageal squamous cell carcinoma - a population-based case-control study in China.

    PubMed

    Chen, Xingdong; Yuan, Ziyu; Lu, Ming; Zhang, Yuechan; Jin, Li; Ye, Weimin

    2017-02-01

    To further examine the association between oral hygiene and esophageal squamous cell carcinoma (ESCC) risk and the effect modification of other exposures, we conducted a population-based case-control study between 2010 and 2012 in Taixing, China, a high-risk area for ESCC. Cases were primarily recruited from endoscopy units at local hospitals, supplemented by linkage to the local Cancer Registry. Control subjects were frequency matched to cases by sex and age (5-year groups) and were randomly selected from the Taixing Population Registry. For the current analysis, data from 616 histopathologically confirmed cases and 770 controls with complete information on oral hygiene were analyzed. Unconditional logistic regression models, including oral hygiene indicators and potential behavioral confounders, were used to derive odds ratios (ORs) and 95% confidence intervals (CIs). Tooth loss was only marginally significantly associated with ESCC risk (yes vs. no, OR = 1.29, 95% CI 0.94-1.74). However, the excess risk increased with increasing numbers of lost teeth (more than 6 teeth lost vs. none, OR = 1.48, 95% CI 1.04-2.11). Tooth brushing once or less per day, compared with tooth brushing twice or more per day, was associated with a 1.81-fold increased risk of ESCC. In the stratification analyses, the increased risks associated with these indicators of oral health were more pronounced in older subjects (age ≥ 70 years), women, non-smokers, and non-drinkers. Further studies are warranted to verify these findings and to explore the underlying mechanisms, e.g., changed oral microbiota, associated with poor oral hygiene. © 2016 UICC.

  1. Effectiveness of the live attenuated rotavirus vaccine produced by a domestic manufacturer in China studied using a population-based case-control design.

    PubMed

    Zhen, Shan-Shan; Li, Yue; Wang, Song-Mei; Zhang, Xin-Jiang; Hao, Zhi-Yong; Chen, Ying; Wang, Dan; Zhang, Yan-Hong; Zhang, Zhi-Yong; Ma, Jing-Chen; Zhou, Peng; Zhang, Zhen; Jiang, Zhi-Wei; Zhao, Yu-Liang; Wang, Xuan-Yi

    2015-10-01

    A universal rotavirus (RV) immunization program is a potentially cost-effective measure for preventing RV infection in China. However, the efficacy of the only licensed RV vaccine (Lanzhou lamb rotavirus vaccine, LLR), which is made by a domestic manufacturer, has not been proven by a properly designed clinical trial. In October 2011 to March 2012, to measure the potential protection provided by LLR, a case-control study nested in a population-based active diarrhea surveillance study of children <5 years of age was conducted in rural Zhengding county. During the study period, 308 episodes of diarrhea were identified as being caused by RV infection, resulting in an incidence rate of 48.0/1000 people/year. The predominant RV serotype was G3 (61.5%), followed by G1 (15.2%), and G9 (6.5%). Overall, a protection of 35.0% (95% confidence interval (CI), 13.0%-52.0%) was identified, and higher protection was found among moderate RV gastroenteritis cases caused by the serotype G3 (52.0% 95% CI: 2.0%-76.1%). A concurrently conducted case-control study comparing non-RV viral diarrheal cases with non-diarrheal controls in the same population found that the RV vaccine offered no protection against non-RV diarrhea. Even under a less ideal immunization schedule, the oral LLR conferred a certain level of protection against RV gastroenteritis. However, further studies are needed to understand the full characteristics of the LLR, including its efficacy when administered following the optimal regimen, the potential risk of inducing intussusception, and the direct and indirect protective effects of LLR.

  2. Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals

    PubMed Central

    Ghani, Mahdi; Reitz, Christiane; Cheng, Rong; Vardarajan, Badri Narayan; Jun, Gyungah; Sato, Christine; Naj, Adam; Rajbhandary, Ruchita; Wang, Li-San; Valladares, Otto; Lin, Chiao-Feng; Larson, Eric B.; Graff-Radford, Neill R.; Evans, Denis; De Jager, Philip L.; Crane, Paul K.; Buxbaum, Joseph D.; Murrell, Jill R.; Raj, Towfique; Ertekin-Taner, Nilufer; Logue, Mark; Baldwin, Clinton T.; Green, Robert C.; Barnes, Lisa L.; Cantwell, Laura B.; Fallin, M. Daniele; Go, Rodney C. P.; Griffith, Patrick A.; Obisesan, Thomas O.; Manly, Jennifer J.; Lunetta, Kathryn L.; Kamboh, M. Ilyas; Lopez, Oscar L.; Bennett, David A.; Hendrie, Hugh; Hall, Kathleen S.; Goate, Alison M.; Byrd, Goldie S.; Kukull, Walter A.; Foroud, Tatiana M.; Haines, Jonathan L.; Farrer, Lindsay A.; Pericak-Vance, Margaret A.; Lee, Joseph H.; Schellenberg, Gerard D.; St. George-Hyslop, Peter; Mayeux, Richard; Rogaeva, Ekaterina

    2015-01-01

    IMPORTANCE Mutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROHs) detectable by single-nucleotide polymorphism (SNP) arrays. OBJECTIVE To evaluate the association between ROHs and AD in an African American population known to have a risk for AD up to 3 times higher than white individuals. DESIGN, SETTING, AND PARTICIPANTS Case-control study of a large African American data set previously genotyped on different genome-wide SNP arrays conducted from December 2013 to January 2015. Global and locus-based ROH measurements were analyzed using raw or imputed genotype data. We studied the raw genotypes from 2 case-control subsets grouped based on SNP array: Alzheimer’s Disease Genetics Consortium data set (871 cases and 1620 control individuals) and Chicago Health and Aging Project–Indianapolis Ibadan Dementia Study data set (279 cases and 1367 control individuals). We then examined the entire data set using imputed genotypes from 1917 cases and 3858 control individuals. MAIN OUTCOMES AND MEASURES The ROHs larger than 1 Mb, 2 Mb, or 3 Mb were investigated separately for global burden evaluation, consensus regions, and gene-based analyses. RESULTS The African American cohort had a low degree of inbreeding (F ~ 0.006). In the Alzheimer’s Disease Genetics Consortium data set, we detected a significantly higher proportion of cases with ROHs greater than 2 Mb (P = .004) or greater than 3 Mb (P = .02), as well as a significant 114-kilobase consensus region on chr4q31.3 (empirical P value 2 = .04; ROHs >2 Mb). In the Chicago Health and Aging Project–Indianapolis Ibadan Dementia Study data set, we identified a significant 202-kilobase consensus region on Chr15q24.1 (empirical P value 2 = .02; ROHs >1 Mb) and a cluster of 13 significant genes on Chr3p21.31 (empirical P value 2 = .03; ROHs >3 Mb). A total of 43 of 49 nominally significant genes common for both data sets also mapped to Chr3p21.31. Analyses of imputed SNP data from the entire data set confirmed the association of AD with global ROH measurements (12.38 ROHs >1 Mb in cases vs 12.11 in controls; 2.986 Mb average size of ROHs >2 Mb in cases vs 2.889 Mb in controls; and 22% of cases with ROHs >3 Mb vs 19% of controls) and a gene-cluster on Chr3p21.31 (empirical P value 2 = .006-.04; ROHs >3 Mb). Also, we detected a significant association between AD and CLDN17 (empirical P value 2 = .01; ROHs >1 Mb), encoding a protein from the Claudin family, members of which were previously suggested as AD biomarkers. CONCLUSIONS AND RELEVANCE To our knowledge, we discovered the first evidence of increased burden of ROHs among patients with AD from an outbred African American population, which could reflect either the cumulative effect of multiple ROHs to AD or the contribution of specific loci harboring recessive mutations and risk haplotypes in a subset of patients. Sequencing is required to uncover AD variants in these individuals. PMID:26366463

  3. Fine mapping of genetic polymorphisms of pulmonary tuberculosis within chromosome 18q11.2 in the Chinese population: a case-control study.

    PubMed

    Dai, Yaoyao; Zhang, Xia; Pan, Hongqiu; Tang, Shaowen; Shen, Hongbing; Wang, Jianming

    2011-10-22

    Recently, one genome-wide association study identified a susceptibility locus of rs4331426 on chromosome 18q11.2 for tuberculosis in the African population. To validate the significance of this susceptibility locus in other areas, we conducted a case-control study in the Chinese population. The present study consisted of 578 cases and 756 controls. The SNP rs4331426 and other six tag SNPs in the 100 Kbp up and down stream of rs4331426 on chromosome 18q11.2 were genotyped by using the Taqman-based allelic discrimination system. As compared with the findings from the African population, genetic variation of the SNP rs4331426 was rare among the Chinese. No significant differences were observed in genotypes or allele frequencies of the tag SNPs between cases and controls either before or after adjusting for age, sex, education, smoking, and drinking history. However, we observed strong linkage disequilibrium of SNPs. Constructed haplotypes within this block were linked the altered risks of tuberculosis. For example, in comparison with the common haplotype AA(rs8087945-rs12456774), haplotypes AG(rs8087945-rs12456774) and GA(rs8087945-rs12456774) were associated with a decreased risk of tuberculosis, with the adjusted odds ratio(95% confidence interval) of 0.34(0.27-0.42) and 0.22(0.16-0.29), respectively. Susceptibility locus of rs4331426 discovered in the African population could not be validated in the Chinese population. None of genetic polymorphisms we genotyped were related to tuberculosis in the single-point analysis. However, haplotypes on chromosome 18q11.2 might contribute to an individual's susceptibility. More work is necessary to identify the true causative variants of tuberculosis.

  4. Methodology Series Module 2: Case-control Studies

    PubMed Central

    Setia, Maninder Singh

    2016-01-01

    Case-Control study design is a type of observational study. In this design, participants are selected for the study based on their outcome status. Thus, some participants have the outcome of interest (referred to as cases), whereas others do not have the outcome of interest (referred to as controls). The investigator then assesses the exposure in both these groups. The investigator should define the cases as specifically as possible. Sometimes, definition of a disease may be based on multiple criteria; thus, all these points should be explicitly stated in case definition. An important aspect of selecting a control is that they should be from the same ‘study base’ as that of the cases. We can select controls from a variety of groups. Some of them are: General population; relatives or friends; and hospital patients. Matching is often used in case-control control studies to ensure that the cases and controls are similar in certain characteristics, and it is a useful technique to increase the efficiency of the study. Case-Control studies can usually be conducted relatively faster and are inexpensive – particularly when compared with cohort studies (prospective). It is useful to study rare outcomes and outcomes with long latent periods. This design is not very useful to study rare exposures. Furthermore, they may also be prone to certain biases – selection bias and recall bias. PMID:27057012

  5. An Examination of the Dynamics of Organizational Culture and Values-Based Leader Identities and Behaviors: One Company's Experience

    ERIC Educational Resources Information Center

    MacTavish, Murray D.; Kolb, Judith A.

    2008-01-01

    This in-depth case study utilized grounded theory methodology to discover how a large privately-owned manufacturing firm in Northeastern USA develops values-based leaders, particularly from minority populations. Over 18 months, interviews with 35 leaders from five levels explored the perceived influence of the environment on leaders' behaviors and…

  6. Analysis of Rare, Exonic Variation amongst Subjects with Autism Spectrum Disorders and Population Controls

    PubMed Central

    Liu, Li; Sabo, Aniko; Neale, Benjamin M.; Nagaswamy, Uma; Stevens, Christine; Lim, Elaine; Bodea, Corneliu A.; Muzny, Donna; Reid, Jeffrey G.; Banks, Eric; Coon, Hillary; DePristo, Mark; Dinh, Huyen; Fennel, Tim; Flannick, Jason; Gabriel, Stacey; Garimella, Kiran; Gross, Shannon; Hawes, Alicia; Lewis, Lora; Makarov, Vladimir; Maguire, Jared; Newsham, Irene; Poplin, Ryan; Ripke, Stephan; Shakir, Khalid; Samocha, Kaitlin E.; Wu, Yuanqing; Boerwinkle, Eric; Buxbaum, Joseph D.; Cook, Edwin H.; Devlin, Bernie; Schellenberg, Gerard D.; Sutcliffe, James S.; Daly, Mark J.; Gibbs, Richard A.; Roeder, Kathryn

    2013-01-01

    We report on results from whole-exome sequencing (WES) of 1,039 subjects diagnosed with autism spectrum disorders (ASD) and 870 controls selected from the NIMH repository to be of similar ancestry to cases. The WES data came from two centers using different methods to produce sequence and to call variants from it. Therefore, an initial goal was to ensure the distribution of rare variation was similar for data from different centers. This proved straightforward by filtering called variants by fraction of missing data, read depth, and balance of alternative to reference reads. Results were evaluated using seven samples sequenced at both centers and by results from the association study. Next we addressed how the data and/or results from the centers should be combined. Gene-based analyses of association was an obvious choice, but should statistics for association be combined across centers (meta-analysis) or should data be combined and then analyzed (mega-analysis)? Because of the nature of many gene-based tests, we showed by theory and simulations that mega-analysis has better power than meta-analysis. Finally, before analyzing the data for association, we explored the impact of population structure on rare variant analysis in these data. Like other recent studies, we found evidence that population structure can confound case-control studies by the clustering of rare variants in ancestry space; yet, unlike some recent studies, for these data we found that principal component-based analyses were sufficient to control for ancestry and produce test statistics with appropriate distributions. After using a variety of gene-based tests and both meta- and mega-analysis, we found no new risk genes for ASD in this sample. Our results suggest that standard gene-based tests will require much larger samples of cases and controls before being effective for gene discovery, even for a disorder like ASD. PMID:23593035

  7. Translational cancer research: balancing prevention and treatment to combat cancer globally.

    PubMed

    Wild, Christopher P; Bucher, John R; de Jong, Bas W D; Dillner, Joakim; von Gertten, Christina; Groopman, John D; Herceg, Zdenko; Holmes, Elaine; Holmila, Reetta; Olsen, Jørgen H; Ringborg, Ulrik; Scalbert, Augustin; Shibata, Tatsuhiro; Smith, Martyn T; Ulrich, Cornelia; Vineis, Paolo; McLaughlin, John

    2015-01-01

    Cancer research is drawing on the human genome project to develop new molecular-targeted treatments. This is an exciting but insufficient response to the growing, global burden of cancer, particularly as the projected increase in new cases in the coming decades is increasingly falling on developing countries. The world is not able to treat its way out of the cancer problem. However, the mechanistic insights from basic science can be harnessed to better understand cancer causes and prevention, thus underpinning a complementary public health approach to cancer control. This manuscript focuses on how new knowledge about the molecular and cellular basis of cancer, and the associated high-throughput laboratory technologies for studying those pathways, can be applied to population-based epidemiological studies, particularly in the context of large prospective cohorts with associated biobanks to provide an evidence base for cancer prevention. This integrated approach should allow a more rapid and informed translation of the research into educational and policy interventions aimed at risk reduction across a population. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study.

    PubMed

    McCourt, C; Coleman, H G; Murray, L J; Cantwell, M M; Dolan, O; Powe, D G; Cardwell, C R

    2014-04-01

    Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers. To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma. Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case-control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing. Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68-1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56-1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality. Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study. © 2014 British Association of Dermatologists.

  9. On the Analysis of Case-Control Studies in Cluster-correlated Data Settings.

    PubMed

    Haneuse, Sebastien; Rivera-Rodriguez, Claudia

    2018-01-01

    In resource-limited settings, long-term evaluation of national antiretroviral treatment (ART) programs often relies on aggregated data, the analysis of which may be subject to ecological bias. As researchers and policy makers consider evaluating individual-level outcomes such as treatment adherence or mortality, the well-known case-control design is appealing in that it provides efficiency gains over random sampling. In the context that motivates this article, valid estimation and inference requires acknowledging any clustering, although, to our knowledge, no statistical methods have been published for the analysis of case-control data for which the underlying population exhibits clustering. Furthermore, in the specific context of an ongoing collaboration in Malawi, rather than performing case-control sampling across all clinics, case-control sampling within clinics has been suggested as a more practical strategy. To our knowledge, although similar outcome-dependent sampling schemes have been described in the literature, a case-control design specific to correlated data settings is new. In this article, we describe this design, discuss balanced versus unbalanced sampling techniques, and provide a general approach to analyzing case-control studies in cluster-correlated settings based on inverse probability-weighted generalized estimating equations. Inference is based on a robust sandwich estimator with correlation parameters estimated to ensure appropriate accounting of the outcome-dependent sampling scheme. We conduct comprehensive simulations, based in part on real data on a sample of N = 78,155 program registrants in Malawi between 2005 and 2007, to evaluate small-sample operating characteristics and potential trade-offs associated with standard case-control sampling or when case-control sampling is performed within clusters.

  10. The home environment and asthma symptoms in childhood: two population based case-control studies 13 years apart

    PubMed Central

    Butland, B. K.; Strachan, D. P.; Anderson, H. R.

    1997-01-01

    BACKGROUND: Prevalence surveys of asthma and/or wheezing among all children aged between 7 1/2 and 8 1/2 attending state and private schools in the London Borough of Croydon were conducted in February 1978 and February 1991. Two population based case-control studies drawn from the survey responders were used to investigate the association between childhood wheeze and characteristics of the home environment and to assess whether changes in these characteristics between 1978 and 1991 may have contributed to an increase in the population prevalence of wheeze among school children. METHODS: Information on exposure to potential indoor environmental risk factors was obtained from parents by home interview and compared between cases-that is, children with frequent (> or = 5) or in-frequent (1-4) attacks of asthma or wheezing in the past 12 months- and controls, with adjustment for study. Changes in exposure over time were assessed by comparing control groups. RESULTS: Between 1978 and 1991 the population prevalence odds of wheeze increased by 20% (OR 1.20; 95% CI 1.04 to 1.39). Change in parental smoking, gas cooking, pet ownership, and central heating did not appear to explain the rise. Use of non-feather pillows was positively associated with childhood wheeze even after adjusting for other risk factors and after re-coding from non-feather to feather cases thought to have changed pillow in response to symptoms (OR 1.54; 95% CI 1.13 to 2.10). The proportion of control children reportedly using non-feather pillows was 44% in 1978 and 67% in 1991. CONCLUSIONS: Increased use of non-feather pillows was the only domestic indoor exposure studied which appeared to explain a modest rise in prevalence of wheeze from 1978 to 1991. Our analysis attempts to address behavioural change in response to the child's symptoms but an artifact arising from lifelong avoidance of feather bedding in atopic families cannot be entirely discounted. 


 PMID:9246133

  11. Online market research panel members as controls in case-control studies to investigate gastrointestinal disease outbreaks: early experiences and lessons learnt from the UK.

    PubMed

    Mook, P; McCormick, J; Kanagarajah, S; Adak, G K; Cleary, P; Elson, R; Gobin, M; Hawker, J; Inns, T; Sinclair, C; Trienekens, S C M; Vivancos, R; McCarthy, N D

    2018-03-01

    Established methods of recruiting population controls for case-control studies to investigate gastrointestinal disease outbreaks can be time consuming, resulting in delays in identifying the source or vehicle of infection. After an initial evaluation of using online market research panel members as controls in a case-control study to investigate a Salmonella outbreak in 2013, this method was applied in four further studies in the UK between 2014 and 2016. We used data from all five studies and interviews with members of each outbreak control team and market research panel provider to review operational issues, evaluate risk of bias in this approach and consider methods to reduce confounding and bias. The investigators of each outbreak reported likely time and cost savings from using market research controls. There were systematic differences between case and control groups in some studies but no evidence that conclusions on the likely source or vehicle of infection were incorrect. Potential selection biases introduced by using this sampling frame and the low response rate are unclear. Methods that might reduce confounding and some bias should be balanced with concerns for overmatching. Further evaluation of this approach using comparisons with traditional methods and population-based exposure survey data is recommended.

  12. Disease-Concordant Twins Empower Genetic Association Studies.

    PubMed

    Tan, Qihua; Li, Weilong; Vandin, Fabio

    2017-01-01

    Genome-wide association studies with moderate sample sizes are underpowered, especially when testing SNP alleles with low allele counts, a situation that may lead to high frequency of false-positive results and lack of replication in independent studies. Related individuals, such as twin pairs concordant for a disease, should confer increased power in genetic association analysis because of their genetic relatedness. We conducted a computer simulation study to explore the power advantage of the disease-concordant twin design, which uses singletons from disease-concordant twin pairs as cases and ordinary healthy samples as controls. We examined the power gain of the twin-based design for various scenarios (i.e., cases from monozygotic and dizygotic twin pairs concordant for a disease) and compared the power with the ordinary case-control design with cases collected from the unrelated patient population. Simulation was done by assigning various allele frequencies and allelic relative risks for different mode of genetic inheritance. In general, for achieving a power estimate of 80%, the sample sizes needed for dizygotic and monozygotic twin cases were one half and one fourth of the sample size of an ordinary case-control design, with variations depending on genetic mode. Importantly, the enriched power for dizygotic twins also applies to disease-concordant sibling pairs, which largely extends the application of the concordant twin design. Overall, our simulation revealed a high value of disease-concordant twins in genetic association studies and encourages the use of genetically related individuals for highly efficiently identifying both common and rare genetic variants underlying human complex diseases without increasing laboratory cost. © 2016 John Wiley & Sons Ltd/University College London.

  13. Epidemiology and the economic assessment of a mumps outbreak in a highly vaccinated population, Orange County, New York, 2009–2010

    PubMed Central

    Kutty, Preeta Krishnan; Lawler, Jacqueline; Rausch-Phung, Elizabeth; Ortega-Sanchez, Ismael R; Goodell, Stephen; Schulte, Cynthia; Pollock, Lynn; Valure, Barbara; Hudson, Jean; Gallagher, Kathleen; Blog, Debra

    2014-01-01

    Studies assessing the economic burden of a mumps outbreak in a highly vaccinated population are limited. The Orange County Health Department (OCHD), New York State Department of Health (NYS DOH), and the Centers for Disease Control and Prevention conducted a mumps investigation in an affected village with a highly vaccinated population. To understand the epidemiology, standardized mumps case definition and active surveillance were used to identify mumps cases. In addition, an economic assessment of a combined outbreak investigation and third dose measles-mumps-rubella (MMR) vaccine intervention conducted by OCHD and NYS DOH was performed; estimated by retrospectively evaluating public health response-related activities including use of a third dose of MMR vaccine. From September 24, 2009, through June 15, 2010, 790 mumps cases were reported—64% were male and highest attack rate was among 11–17 year age group (99.1 cases per 1000 individuals). Of the 658 cases with known vaccination history, 83.6% had documentation of 2 doses of mumps containing vaccine. No deaths were reported. The 2 major exposure settings were schools (71.8%) and households (22.5%). Approximately 7736 h of public health personnel time were expended with the total approximate cost of US $463 000, including US $34 392 for MMR vaccine—the estimated cost per household was US $827. Mumps continues to be endemic in many parts of the world, resulting in importations into the United States. Large mumps outbreaks similar to this in highly vaccinated populations may require considerable investigation and control activities. PMID:24633360

  14. Epidemiology and the economic assessment of a mumps outbreak in a highly vaccinated population, Orange County, New York, 2009-2010.

    PubMed

    Kutty, Preeta Krishnan; Lawler, Jacqueline; Rausch-Phung, Elizabeth; Ortega-Sanchez, Ismael R; Goodell, Stephen; Schulte, Cynthia; Pollock, Lynn; Valure, Barbara; Hudson, Jean; Gallagher, Kathleen; Blog, Debra

    2014-01-01

    Studies assessing the economic burden of a mumps outbreak in a highly vaccinated population are limited. The Orange County Health Department (OCHD), New York State Department of Health (NYS DOH), and the Centers for Disease Control and Prevention conducted a mumps investigation in an affected village with a highly vaccinated population. To understand the epidemiology, standardized mumps case definition and active surveillance were used to identify mumps cases. In addition, an economic assessment of a combined outbreak investigation and third dose measles-mumps-rubella (MMR) vaccine intervention conducted by OCHD and NYS DOH was performed; estimated by retrospectively evaluating public health response-related activities including use of a third dose of MMR vaccine. From September 24, 2009, through June 15, 2010, 790 mumps cases were reported-64% were male and highest attack rate was among 11-17 year age group (99.1 cases per 1000 individuals). Of the 658 cases with known vaccination history, 83.6% had documentation of 2 doses of mumps containing vaccine. No deaths were reported. The 2 major exposure settings were schools (71.8%) and households (22.5%). Approximately 7736 h of public health personnel time were expended with the total approximate cost of US $463,000, including US $34,392 for MMR vaccine-the estimated cost per household was US $827. Mumps continues to be endemic in many parts of the world, resulting in importations into the United States. Large mumps outbreaks similar to this in highly vaccinated populations may require considerable investigation and control activities.

  15. Spatiotemporal air pollution exposure assessment for a Canadian population-based lung cancer case-control study

    PubMed Central

    2012-01-01

    Background Few epidemiological studies of air pollution have used residential histories to develop long-term retrospective exposure estimates for multiple ambient air pollutants and vehicle and industrial emissions. We present such an exposure assessment for a Canadian population-based lung cancer case-control study of 8353 individuals using self-reported residential histories from 1975 to 1994. We also examine the implications of disregarding and/or improperly accounting for residential mobility in long-term exposure assessments. Methods National spatial surfaces of ambient air pollution were compiled from recent satellite-based estimates (for PM2.5 and NO2) and a chemical transport model (for O3). The surfaces were adjusted with historical annual air pollution monitoring data, using either spatiotemporal interpolation or linear regression. Model evaluation was conducted using an independent ten percent subset of monitoring data per year. Proximity to major roads, incorporating a temporal weighting factor based on Canadian mobile-source emission estimates, was used to estimate exposure to vehicle emissions. A comprehensive inventory of geocoded industries was used to estimate proximity to major and minor industrial emissions. Results Calibration of the national PM2.5 surface using annual spatiotemporal interpolation predicted historical PM2.5 measurement data best (R2 = 0.51), while linear regression incorporating the national surfaces, a time-trend and population density best predicted historical concentrations of NO2 (R2 = 0.38) and O3 (R2 = 0.56). Applying the models to study participants residential histories between 1975 and 1994 resulted in mean PM2.5, NO2 and O3 exposures of 11.3 μg/m3 (SD = 2.6), 17.7 ppb (4.1), and 26.4 ppb (3.4) respectively. On average, individuals lived within 300 m of a highway for 2.9 years (15% of exposure-years) and within 3 km of a major industrial emitter for 6.4 years (32% of exposure-years). Approximately 50% of individuals were classified into a different PM2.5, NO2 and O3 exposure quintile when using study entry postal codes and spatial pollution surfaces, in comparison to exposures derived from residential histories and spatiotemporal air pollution models. Recall bias was also present for self-reported residential histories prior to 1975, with cases recalling older residences more often than controls. Conclusions We demonstrate a flexible exposure assessment approach for estimating historical air pollution concentrations over large geographical areas and time-periods. In addition, we highlight the importance of including residential histories in long-term exposure assessments. For submission to: Environmental Health PMID:22475580

  16. Sitting occupations are an independent risk factor for Ischemic stroke in North Indian population.

    PubMed

    Kumar, A; Prasad, M; Kathuria, P

    2014-10-01

    Stroke is a multi-factorial disease and is influenced by complex environmental interactions. The purpose of this case-control study was to determine the relationship of sitting occupations with ischemic stroke in the North Indian population. In a hospital-based case-control study, age- and sex-matched controls were recruited from the outpatient department and the neurology ward of All India Institute of Medical Sciences, New Delhi. Occupation along with other demographic and risk factor variables was measured in-person interview in standardized case record form. The multivariate logistic regression model was used to estimate the odds ratio associated with ischemic stroke. Two hundred and twenty-four people post-stroke and 224 control participants were recruited from the period of February 2009 to February 2012. Mean age of cases and controls was 53.47 ± 14 and 52.92 ± 13.4, respectively. The occupations which involve sitting at work were independently associated with the risk of ischemic stroke after adjustment for demographic and risk factor variables (OR 2.2, 95% CI 1.12-3.8). The result of this study has shown an independent association between the sitting occupations and ischemic stroke in North Indian population. The present study supports the workplace health initiative to implement workplace physical activity policy and encourages employee to reduce the amount of time they spend sitting throughout the day.

  17. Sugary food and beverage consumption and epithelial ovarian cancer risk: a population-based case-control study.

    PubMed

    King, Melony G; Olson, Sara H; Paddock, Lisa; Chandran, Urmila; Demissie, Kitaw; Lu, Shou-En; Parekh, Niyati; Rodriguez-Rodriguez, Lorna; Bandera, Elisa V

    2013-02-27

    Ovarian cancer is the deadliest gynecologic cancer in the US. The consumption of refined sugars has increased dramatically over the past few decades, accounting for almost 15% of total energy intake. Yet, there is limited evidence on how sugar consumption affects ovarian cancer risk. We evaluated ovarian cancer risk in relation to sugary foods and beverages, and total and added sugar intakes in a population-based case-control study. Cases were women with newly diagnosed epithelial ovarian cancer, older than 21 years, able to speak English or Spanish, and residents of six counties in New Jersey. Controls met same criteria as cases, but were ineligible if they had both ovaries removed. A total of 205 cases and 390 controls completed a phone interview, food frequency questionnaire, and self-recorded waist and hip measurements. Based on dietary data, we computed the number of servings of dessert foods, non-dessert foods, sugary drinks and total sugary foods and drinks for each participant. Total and added sugar intakes (grams/day) were also calculated. Multiple logistic regression models were used to estimate odds ratios and 95% confidence intervals for food and drink groups and total and added sugar intakes, while adjusting for major risk factors. We did not find evidence of an association between consumption of sugary foods and beverages and risk, although there was a suggestion of increased risk associated with sugary drink intake (servings per 1,000 kcal; OR=1.63, 95% CI: 0.94-2.83). Overall, we found little indication that sugar intake played a major role on ovarian cancer development.

  18. Sex-specific impact of socio-economic factors on suicide risk: a population-based case-control study in Denmark.

    PubMed

    Andrés, Antonio Rodríguez; Collings, Sunny; Qin, Ping

    2010-06-01

    Although many authors have investigated the impact of sex on the association between socio-economic status (SES) and suicide, a definite consensus has not yet emerged. Using Danish population registration data including 15 648 suicide deaths of individuals aged 18-65 year during 1981-97 and matched population controls, we investigate the associations of multiple SES factors with suicide risk and explore the sex-specific aspects of these associations. We use conditional logistic regression models to estimate the statistical relationship between SES, sex and suicide. SES, proxied by low income, unskilled blue-collar work, non-specific wage work and unemployment, increases suicide risk more prominently for men than for women. Marital status has a comparable influence on suicide risk in both sexes; parenthood is protective against suicide, and the effect is larger for women. Living in a large city raises suicide risk for women but reduces it for men; residents with a foreign citizenship in Denmark have a lower risk of suicide compared with Danish citizens, but this protection is confined to male immigrants. Our results demonstrate that suicide risk is associated with a range of SES proxies but the strength and/or direction of the association can differ by sex. Risk assessment and, therefore, prevention approaches should take this into consideration.

  19. No association between FOXP2 rs10447760 and schizophrenia in a replication study of the Chinese Han population.

    PubMed

    Yin, Jiajun; Jia, Ningren; Liu, Yansong; Jin, Chunhui; Zhang, Fuquan; Yu, Shui; Wang, Jun; Yuan, Jianmin

    2018-04-01

    Schizophrenia (SCZ) is a severe and heritable psychiatric disorder, and previous studies have shown that regulation of the forkhead-box P2 gene (FOXP2) may play a role in schizophrenia. Moreover, just a few studies have identified a single nucleotide polymorphism (SNP) rs10447760 within the gene that was a risk variant for SCZ in the Chinese Han population. To examine whether the variant in the FOXP2 gene contributes toward SCZ susceptibility, we carried out an association analysis of the SNP rs10447760 of the FOXP2 gene in a case-control study (1405 cases, 1137 controls) from China. We identified no association of rs10447760 in the FOXP2 gene with SCZ (all P>0.05). In addition, a meta-analysis indicated that the SNP rs10447760 was not associated with susceptibility to SCZ in Han Chinese populations (pooled odds ratio=1.44, 95% confidence interval: 0.63-3.31, P=0.39). Thus, our results did not support the association between FOXP2 rs10447760 and schizophrenia in a Chinese Han population, and large-scale genetic replication studies with different racial and geographic origins are required in the future.

  20. Risk of tinnitus in patients with sleep apnea: A nationwide, population-based, case-control study.

    PubMed

    Koo, Malcolm; Hwang, Juen-Haur

    2017-09-01

    To investigate the risk of tinnitus in patients with sleep disturbance or sleep apnea. Case control study. We identified 21,798 middle-aged and elderly patients with otolaryngologist-diagnosed tinnitus between January 1, 2000, and December 31, 2012, from the Longitudinal Health Insurance Database 2000 of the Taiwan National Health Insurance Research Database. A total of 108,990 controls were also identified from the same database based on frequency-matching on 10-year age interval, sex, and year of index date of the cases. Diagnoses of sleep disturbance (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] codes 780.50, 780.52, 307.4) and sleep apnea (ICD-9-CM codes 780.51, 780.53, 780.57) in the cases and controls prior to the index date were assessed. The risks of tinnitus in patients with sleep disturbance and sleep apnea were separately evaluated with multivariate logistic regression analyses. The mean age of the total 130,788 patients was 59.8 years, and 47% of them were males. The risk of tinnitus was higher in patients with sleep disturbance compared to those without the condition (adjusted odds ratio [OR] = 1.13, 95% confidence interval [CI] [95% CI] = 1.11-1.17), and the risk of tinnitus was higher in patients with sleep apnea compared to those without the condition (adjusted OR = 1.36, 95% CI = 1.16-1.60). In this population-based, case-control study, the risk of tinnitus was found to be significantly higher among middle-aged and elderly Taiwanese patients with sleep disturbances, especially with sleep apnea. 3b. Laryngoscope, 127:2171-2175, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  1. An individual-based model for population viability analysis of humpback chub in Grand Canyon

    USGS Publications Warehouse

    Pine, William Pine; Healy, Brian; Smith, Emily Omana; Trammell, Melissa; Speas, Dave; Valdez, Rich; Yard, Mike; Walters, Carl; Ahrens, Rob; Vanhaverbeke, Randy; Stone, Dennis; Wilson, Wade

    2013-01-01

    We developed an individual-based population viability analysis model (females only) for evaluating risk to populations from catastrophic events or conservation and research actions. This model tracks attributes (size, weight, viability, etc.) for individual fish through time and then compiles this information to assess the extinction risk of the population across large numbers of simulation trials. Using a case history for the Little Colorado River population of Humpback Chub Gila cypha in Grand Canyon, Arizona, we assessed extinction risk and resiliency to a catastrophic event for this population and then assessed a series of conservation actions related to removing specific numbers of Humpback Chub at different sizes for conservation purposes, such as translocating individuals to establish other spawning populations or hatchery refuge development. Our results suggested that the Little Colorado River population is generally resilient to a single catastrophic event and also to removals of larvae and juveniles for conservation purposes, including translocations to establish new populations. Our results also suggested that translocation success is dependent on similar survival rates in receiving and donor streams and low emigration rates from recipient streams. In addition, translocating either large numbers of larvae or small numbers of large juveniles has generally an equal likelihood of successful population establishment at similar extinction risk levels to the Little Colorado River donor population. Our model created a transparent platform to consider extinction risk to populations from catastrophe or conservation actions and should prove useful to managers assessing these risks for endangered species such as Humpback Chub.

  2. Urban parasitology: visceral leishmaniasis in Brazil.

    PubMed

    Harhay, Michael O; Olliaro, Piero L; Costa, Dorcas Lamounier; Costa, Carlos Henrique Nery

    2011-09-01

    Since the early 1980s, visceral leishmaniasis (VL) which is, in general, a rural zoonotic disease, has spread to the urban centers of the north, and now the south and west of Brazil. The principal drivers differ between cities, though human migration, large urban canid populations (animal reservoir), and a decidedly peripatetic and adaptable sand fly vector are the primary forces. The exact number of urban cases remains unclear as a result of challenges with surveillance. However, the number of urban cases registered continues to increase annually. Most control initiatives (e.g. culling infected dogs and household spraying to kill the sand fly) could be effective, but have proven hard to maintain at large scales due to logistical, financial and other reasons. In this article, the urbanization of VL in Brazil is reviewed, touching on these and other topics related to controlling VL within and outside Brazil. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. A matched case-control study of convenience store robbery risk factors.

    PubMed

    Hendricks, S A; Landsittel, D P; Amandus, H E; Malcan, J; Bell, J

    1999-11-01

    Convenience store clerks have been shown to be at high risk for assault and homicide, mostly owing to robbery or robbery attempts. Although the literature consistently indicates that at least some environmental designs are effective deterrents of robbery, the significance of individual interventions and policies has differed across past studies. To address these issues, a matched case-control study of 400 convenience store robberies in three metropolitan areas of Virginia was conducted. Conditional logistic regression was implemented to evaluate the significance of various environmental designs and other factors possibly related to convenience store robbery. Findings indicate that numerous characteristics of the surrounding environment and population were significantly associated with convenience store robbery. Results also showed that, on a univariate level, most crime prevention factors were significantly associated with a lower risk for robbery. Using a forward selection process, a multivariate model, which included cash handling policy, bullet-resistant shielding, and numerous characteristics of the surrounding area and population, was identified. This study addressed numerous limitations of the previous literature by prospectively collecting extensive data on a large sample of diverse convenience stores and directly addressing the current theory on the robbers' selection of a target store through a matched case-control design.

  4. An agent-based modeling framework for evaluating hypotheses on risks for developing autism: effects of the gut microbial environment.

    PubMed

    Weston, Bronson; Fogal, Benjamin; Cook, Daniel; Dhurjati, Prasad

    2015-04-01

    The number of cases diagnosed with Autism Spectrum Disorders is rising at an alarming rate with the Centers for Disease Control estimating the 2014 incidence rate as 1 in 68. Recently, it has been hypothesized that gut bacteria may contribute to the development of autism. Specifically, the relative balances between the inflammatory microbes clostridia and desulfovibrio and the anti-inflammatory microbe bifidobacteria may become destabilized prior to autism development. The imbalance leads to a leaky gut, characterized by a more porous epithelial membrane resulting in microbial toxin release into the blood, which may contribute to brain inflammation and autism development. To test how changes in population dynamics of the gut microbiome may lead to the imbalanced microbial populations associated with autism patients, we constructed a novel agent-based model of clostridia, desulfovibrio, and bifidobacteria population interactions in the gut. The model demonstrates how changing physiological conditions in the gut can affect the population dynamics of the microbiome. Simulations using our agent-based model indicate that despite large perturbations to initial levels of bacteria, the populations robustly achieve a single steady-state given similar gut conditions. These simulation results suggests that disturbance such as a prebiotic or antibiotic treatment may only transiently affect the gut microbiome. However, sustained prebiotic treatments may correct low population counts of bifidobacteria. Furthermore, our simulations suggest that clostridia growth rate is a key determinant of risk of autism development. Treatment of high-risk infants with supra-physiological levels of lysozymes may suppress clostridia growth rate, resulting in a steep decrease in the clostridia population and therefore reduced risk of autism development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Size matters: insights from an allometric approach to evaluate control methods for invasive Australian Rhinella marina.

    PubMed

    Beaty, Lynne E; Salice, Christopher J

    2013-10-01

    Invasive species are costly and difficult to control. In order to gain a mechanistic understanding of potential control measures, individual-based models uniquely parameterized to reflect the salient life-history characteristics of invasive species are useful. Using invasive Australian Rhinella marina as a case study, we constructed a cohort- and individual-based population simulation that incorporates growth and body size of terrestrial stages. We used this allometric approach to examine the efficacy of nontraditional control methods (i.e., tadpole alarm chemicals and native meat ants) that may have indirect effects on population dynamics mediated by effects on body size. We compared population estimates resulting from these control methods with traditional hand removal. We also conducted a sensitivity analysis to investigate the effect that model parameters, specifically those associated with growth and body size, had on adult population estimates. Incremental increases in hand removal of adults and juveniles caused nonlinear decreases in adult population estimates, suggesting less return with increased investment in hand-removal efforts. Applying tadpole alarm chemicals or meat ants decreased adult population estimates on the same level as removing 15-25% of adults and juveniles by hand. The combined application of tadpole alarm chemicals and meat ants resulted in approximately 80% decrease in adult abundance, the largest of any applied control method. In further support of the nontraditional control methods, which greatly affected the metamorph stage, our model was most sensitive to changes in metamorph survival, juvenile survival, metamorph growth rate, and adult survival. Our results highlight the use and insights that can be gained from individual-based models that incorporate growth and body size and the potential success that nontraditional control methods could have in controlling established, invasive Rhinella marina populations.

  6. Early Statin Use and the Progression of Alzheimer Disease: A Total Population-Based Case-Control Study.

    PubMed

    Lin, Feng-Cheng; Chuang, Yun-Shiuan; Hsieh, Hui-Min; Lee, Tzu-Chi; Chiu, Kuei-Fen; Liu, Ching-Kuan; Wu, Ming-Tsang

    2015-11-01

    The protective effect of statin on Alzheimer disease (AD) is still controversial, probably due to the debate about when to start the use of statin and the lack of any large-scale randomized evidence that actually supports the hypothesis. The purpose of this study was to examine the protective effect of early statin use on mild-to-moderate AD in the total Taiwanese population.This was a total population-based case-control study, using the total population of Taiwanese citizens seen in general medical practice; therefore, the findings can be applied to the general population. The study patients were those with newly diagnosed dementia (ICD-9 290.x) and prescribed any acetylcholinesterase inhibitors (AChEI) from the Taiwan National Health Insurance dataset in 1997 to 2008. The newly diagnosed eligible mild-to-moderate AD patients were traced from the dates of their index dates, which was defined as the first day to receive any AChEI treatment, back to 1 year (exposure period) to categorize them into AD with early statin use and without early statin use. Early statin use was defined as patients using statin before AChEI treatment. Alzheimer disease patients with early statin use were those receiving any statin treatment during the exposure period. Then, we used propensity-score-matched strategy to match these 2 groups as 1:1. The matched study patients were followed-up from their index dates. The primary outcome was the discontinuation of AChEI treatment, indicating AD progression.There were 719 mild-to-moderate AD-paired patients with early statin use and without early statin use for analyses. Alzheimer disease progression was statistically lower in AD patients with early statin use than those without (P = 0.00054). After adjusting for other covariates, mild-to-moderate AD patients with early stain use exhibited a 0.85-risk (95% CI = 0.76-0.95, P = 0.0066) to have AD progression than those without.Early statin use was significantly associated with a reduction in AD progression in mild-to-moderate AD patients. The future randomized trial studies can confirm our findings.

  7. Diagnostic Tests to Support Late-Stage Control Programs for Schistosomiasis and Soil-Transmitted Helminthiases.

    PubMed

    Hawkins, Kenneth R; Cantera, Jason L; Storey, Helen L; Leader, Brandon T; de Los Santos, Tala

    2016-12-01

    Global efforts to address schistosomiasis and soil-transmitted helminthiases (STH) include deworming programs for school-aged children that are made possible by large-scale drug donations. Decisions on these mass drug administration (MDA) programs currently rely on microscopic examination of clinical specimens to determine the presence of parasite eggs. However, microscopy-based methods are not sensitive to the low-intensity infections that characterize populations that have undergone MDA. Thus, there has been increasing recognition within the schistosomiasis and STH communities of the need for improved diagnostic tools to support late-stage control program decisions, such as when to stop or reduce MDA. Failure to adequately address the need for new diagnostics could jeopardize achievement of the 2020 London Declaration goals. In this report, we assess diagnostic needs and landscape potential solutions and determine appropriate strategies to improve diagnostic testing to support control and elimination programs. Based upon literature reviews and previous input from experts in the schistosomiasis and STH communities, we prioritized two diagnostic use cases for further exploration: to inform MDA-stopping decisions and post-MDA surveillance. To this end, PATH has refined target product profiles (TPPs) for schistosomiasis and STH diagnostics that are applicable to these use cases. We evaluated the limitations of current diagnostic methods with regards to these use cases and identified candidate biomarkers and diagnostics with potential application as new tools. Based on this analysis, there is a need to develop antigen-detecting rapid diagnostic tests (RDTs) with simplified, field-deployable sample preparation for schistosomiasis. Additionally, there is a need for diagnostic tests that are more sensitive than the current methods for STH, which may include either a field-deployable molecular test or a simple, low-cost, rapid antigen-detecting test.

  8. Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population

    PubMed Central

    Oh, Il Hwan; Choi, Eun Young; Park, Joon-Sung; Lee, Chang Hwa

    2016-01-01

    Ferritin is considered to be a marker of the body’s iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, population-based, case-control study (KNHNES IV and V). All native Koreans aged ≥ 20 years and who had no medical illness were eligible to participate. Among them, 2.9% had AMD, and its prevalence was found to increase in the higher ferritin quintile groups (Ptrend < 0.0001). In multiple linear regression analysis, serum ferritin level was closely related to conventional risk factors for AMD. Comparison of early AMD with a control group showed that serum ferritin levels were closely associated with AMD (OR = 1.004, 95% CI = 1.002–1.006), and further adjustment for age, gender, serum iron, and kidney function did not reduce this association (OR = 1.003, 95% CI = 1.001–1.006). Furthermore, the relationship between ferritin quintile and early AMD was dose-dependent. Thus, an increased level of serum ferritin in a healthy person may be a useful indicator of neurodegenerative change in the macula. A large population-based prospective clinical study is needed to confirm these findings. PMID:27096155

  9. Evolutionary Computation with Spatial Receding Horizon Control to Minimize Network Coding Resources

    PubMed Central

    Leeson, Mark S.

    2014-01-01

    The minimization of network coding resources, such as coding nodes and links, is a challenging task, not only because it is a NP-hard problem, but also because the problem scale is huge; for example, networks in real world may have thousands or even millions of nodes and links. Genetic algorithms (GAs) have a good potential of resolving NP-hard problems like the network coding problem (NCP), but as a population-based algorithm, serious scalability and applicability problems are often confronted when GAs are applied to large- or huge-scale systems. Inspired by the temporal receding horizon control in control engineering, this paper proposes a novel spatial receding horizon control (SRHC) strategy as a network partitioning technology, and then designs an efficient GA to tackle the NCP. Traditional network partitioning methods can be viewed as a special case of the proposed SRHC, that is, one-step-wide SRHC, whilst the method in this paper is a generalized N-step-wide SRHC, which can make a better use of global information of network topologies. Besides the SRHC strategy, some useful designs are also reported in this paper. The advantages of the proposed SRHC and GA for the NCP are illustrated by extensive experiments, and they have a good potential of being extended to other large-scale complex problems. PMID:24883371

  10. Retrospective multicenter matched case-control study on the risk factors for narcolepsy with special focus on vaccinations (including pandemic influenza vaccination) and infections in Germany.

    PubMed

    Oberle, Doris; Pavel, Jutta; Mayer, Geert; Geisler, Peter; Keller-Stanislawski, Brigitte

    2017-06-01

    Studies associate pandemic influenza vaccination with narcolepsy. In Germany, a retrospective, multicenter, matched case-control study was performed to identify risk factors for narcolepsy, particularly regarding vaccinations (seasonal and pandemic influenza vaccination) and infections (seasonal and pandemic influenza) and to quantify the detected risks. Patients with excessive daytime sleepiness who had been referred to a sleep center between April 2009 and December 2012 for multiple sleep latency test (MSLT) were eligible. Case report forms were validated according to the criteria for narcolepsy defined by the Brighton Collaboration (BC). Confirmed cases of narcolepsy (BC level of diagnostic certainty 1-4a) were matched with population-based controls by year of birth, gender, and place of residence. A second control group was established including patients in whom narcolepsy was definitely excluded (test-negative controls). A total of 103 validated cases of narcolepsy were matched with 264 population-based controls. The second control group included 29 test-negative controls. A significantly increased odd ratio (OR) to develop narcolepsy (crude OR [cOR] = 3.9, 95% confidence interval [CI] = 1.8-8.5; adjusted OR [aOR] = 4.5, 95% CI = 2.0-9.9) was detected in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset as compared to nonvaccinated individuals. Using test-negative controls, in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset, a nonsignificantly increased OR of narcolepsy was detected when compared to nonvaccinated individuals (whole study population, BC levels 1-4a: cOR = 1.9, 95% CI = 0.5-6.9; aOR = 1.8, 95% CI = 0.3-10.1). The findings of this study support an increased risk for narcolepsy after immunization with pandemic influenza A/H1N1/v vaccine. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Socioeconomic conditions among long-term gynaecological cancer survivors--a population-based case-control study.

    PubMed

    Platou, Toril Forbord; Skjeldestad, Finn Egil; Rannestad, Toril

    2010-03-01

    The population of gynaecological cancer survivors is growing, yet little is known about the effects of cancer and treatment on socioeconomic conditions well beyond the completion of therapy. The aim of this study was to investigate the socioeconomic conditions in long-term survivors of gynaecological cancer compared with a representative group of women from the general population. The study comprises women aged 32-75 residing in central part of Norway and who were treated as primary cases of gynaecological cancer at the University Hospital in Trondheim, Norway (n=160), and a control group from the general population (n=493). All analyses were done by chi(2) test and logistic regression. Gynaecological cancer survivors scored lower on a Socioeconomic Condition Index than the control group. They had on the average a complete remission period of 12 years. Compared with the control group, they were more often disabled (p<0.01) and had lower annual household income (p<0.01). No difference was detected between the groups in ability to pay bills. More cases than controls had experienced problems assigning personal insurance (p<0.03). Long-term gynaecological cancer survivors lived under poorer socioeconomic conditions, were more often disabled and had lower annual household income than the women in the control group, whereas no difference in ability to pay bills were found between the groups. In spite of poorer socioeconomic conditions, the gynaecological cancer survivors seem to adapt well to their financial situation.

  12. Health care seeking for Childhood Diarrhea in Developing Countries: Evidence from Seven Sites in Africa and Asia

    PubMed Central

    Nasrin, Dilruba; Wu, Yukun; Blackwelder, William C.; Farag, Tamer H.; Saha, Debasish; Sow, Samba O.; Alonso, Pedro L.; Breiman, Robert F.; Sur, Dipika; Faruque, Abu S. G.; Zaidi, Anita K. M.; Biswas, Kousick; Van Eijk, Anna Maria; Walker, Damian G.; Levine, Myron M.; Kotloff, Karen L.

    2013-01-01

    We performed serial Health Care Utilization and Attitudes Surveys (HUASs) among caretakers of children ages 0–59 months randomly selected from demographically defined populations participating in the Global Enteric Multicenter Study (GEMS), a case-control study of moderate-to-severe diarrhea (MSD) in seven developing countries. The surveys aimed to estimate the proportion of children with MSD who would present to sentinel health centers (SHCs) where GEMS case recruitment would occur and provide a basis for adjusting disease incidence rates to include cases not seen at the SHCs. The proportion of children at each site reported to have had an incident episode of MSD during the 7 days preceding the survey ranged from 0.7% to 4.4% for infants (0–11 months of age), from 0.4% to 4.7% for toddlers (12–23 months of age), and from 0.3% to 2.4% for preschoolers (24–59 months of age). The proportion of MSD episodes at each site taken to an SHC within 7 days of diarrhea onset was 15–56%, 17–64%, and 7–33% in the three age strata, respectively. High cost of care and insufficient knowledge about danger signs were associated with lack of any care-seeking outside the home. Most children were not offered recommended fluids and continuing feeds at home. We have shown the utility of serial HUASs as a tool for optimizing operational and methodological issues related to the performance of a large case-control study and deriving population-based incidence rates of MSD. Moreover, the surveys suggest key targets for educational interventions that might improve the outcome of diarrheal diseases in low-resource settings. PMID:23629939

  13. Whole exome sequencing in 75 high-risk families with validation and replication in independent case-control studies identifies TANGO2, OR5H14, and CHAD as new prostate cancer susceptibility genes.

    PubMed

    Karyadi, Danielle M; Geybels, Milan S; Karlins, Eric; Decker, Brennan; McIntosh, Laura; Hutchinson, Amy; Kolb, Suzanne; McDonnell, Shannon K; Hicks, Belynda; Middha, Sumit; FitzGerald, Liesel M; DeRycke, Melissa S; Yeager, Meredith; Schaid, Daniel J; Chanock, Stephen J; Thibodeau, Stephen N; Berndt, Sonja I; Stanford, Janet L; Ostrander, Elaine A

    2017-01-03

    Prostate cancer (PCa) susceptibility is defined by a continuum from rare, high-penetrance to common, low-penetrance alleles. Research to date has concentrated on identification of variants at the ends of that continuum. Taking an alternate approach, we focused on the important but elusive class of low-frequency, moderately penetrant variants by performing disease model-based variant filtering of whole exome sequence data from 75 hereditary PCa families. Analysis of 341 candidate risk variants identified nine variants significantly associated with increased PCa risk in a population-based, case-control study of 2,495 men. In an independent nested case-control study of 7,121 men, there was risk association evidence for TANGO2 p.Ser17Ter and the established HOXB13 p.Gly84Glu variant. Meta-analysis combining the case-control studies identified two additional variants suggestively associated with risk, OR5H14 p.Met59Val and CHAD p.Ala342Asp. The TANGO2 and HOXB13 variants co-occurred in cases more often than expected by chance and never in controls. Finally, TANGO2 p.Ser17Ter was associated with aggressive disease in both case-control studies separately. Our analyses identified three new PCa susceptibility alleles in the TANGO2, OR5H14 and CHAD genes that not only segregate in multiple high-risk families but are also of importance in altering disease risk for men from the general population. This is the first successful study to utilize sequencing in high-risk families for the express purpose of identifying low-frequency, moderately penetrant PCa risk mutations.

  14. A population-based case-control study on statin exposure and risk of acute diverticular disease.

    PubMed

    Sköldberg, Filip; Svensson, Tobias; Olén, Ola; Hjern, Fredrik; Schmidt, Peter T; Ljung, Rickard

    2016-01-01

    A reduced risk of perforated diverticular disease among individuals with current statin exposure has been reported. The aim of the present study was to investigate whether statins reduce the risk of acute diverticular disease. A nation-wide population-based case-control study was performed, including 13,127 cases hospitalised during 2006-2010 with a first-time diagnosis of colonic diverticular disease, and 128,442 control subjects (matched for sex, age, county of residence and calendar year). Emergency surgery, assumed to be a proxy for complicated diverticulitis, was performed on 906 of the cases during the index admission, with 8818 matched controls. Statin exposure was classified as "current" or "former" if a statin prescription was last dispensed ≤ 125 days or >125 days before index date, respectively. The association between statin exposure and acute diverticular disease was investigated by conditional logistic regression, including models adjusting for country of birth, educational level, marital status, comorbidities, nonsteroidal anti-inflammatory drug/steroid exposure and healthcare utilisation. A total of 1959 cases (14.9%) and 16,456 controls (12.8%) were current statin users (crude OR 1.23 [95% CI 1.17-1.30]; fully adjusted OR 1.00 [0.94-1.06]). One hundred and thirty-two of the cases subjected to surgery (14.6%), and 1441 of the corresponding controls (16.3%) were current statin users (crude OR 0.89 [95% CI 0.73-1.08]; fully adjusted OR 0.70 [0.55-0.89]). The results do not indicate that statins affect the development of symptomatic diverticular disease in general. However, current statin use was associated with a reduced risk of emergency surgery for diverticular disease.

  15. An approach of the exact linearization techniques to analysis of population dynamics of the mosquito Aedes aegypti.

    PubMed

    Dos Reis, Célia A; Florentino, Helenice de O; Cólon, Diego; Rosa, Suélia R Fleury; Cantane, Daniela R

    2018-05-01

    Dengue fever, chikungunya and zika are caused by different viruses and mainly transmitted by Aedes aegypti mosquitoes. These diseases have received special attention of public health officials due to the large number of infected people in tropical and subtropical countries and the possible sequels that those diseases can cause. In severe cases, the infection can have devastating effects, affecting the central nervous system, muscles, brain and respiratory system, often resulting in death. Vaccines against these diseases are still under development and, therefore, current studies are focused on the treatment of diseases and vector (mosquito) control. This work focuses on this last topic, and presents the analysis of a mathematical model describing the population dynamics of Aedes aegypti, as well as present the design of a control law for the mosquito population (vector control) via exact linearization techniques and optimal control. This control strategy optimizes the use of resources for vector control, and focuses on the aquatic stage of the mosquito life. Theoretical and computational results are also presented. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Stroke incidence is decreasing in whites but not in blacks: a population-based estimate of temporal trends in stroke incidence from the Greater Cincinnati/Northern Kentucky Stroke Study.

    PubMed

    Kleindorfer, Dawn O; Khoury, Jane; Moomaw, Charles J; Alwell, Kathleen; Woo, Daniel; Flaherty, Matthew L; Khatri, Pooja; Adeoye, Opeolu; Ferioli, Simona; Broderick, Joseph P; Kissela, Brett M

    2010-07-01

    Although other studies (in largely white populations) have found that stroke incidence declined during the 1990s, we previously reported that stroke incidence in our population (18% of which was black) did not change during that decade and that incidence rates in blacks were significantly higher than in whites. We sought to update temporal trends in stroke incidence by adding new data obtained from our large, biracial population in 2005. The objective of this study was to examine temporal trends in stroke incidence and case-fatality within a large biracial population over time by comparing stroke incidence rates from 1993 to 1994, 1999, and 2005. Within the Greater Cincinnati/Northern Kentucky population of 1.3 million, all strokes among area residents were ascertained at all local hospitals during July 1993 to June 19/94 and calendar years 1999 and 2005. A sampling scheme was used to ascertain cases in the out-of-hospital setting. Only first-ever strokes were included in this analysis. Race-specific incidence rates, standardized to the 2000 US Census population, and case-fatality rates were calculated. The number of physician-confirmed first-ever strokes in patients >or=20 years of age was 1942 in 1993 to 1994, 2041 in 1999, and 1921 in 2005. In all study periods, blacks had higher stroke incidence than whites, and case-fatality rates were similar between races. In contrast to previous study periods, we found a significant decrease in overall stroke incidence in 2005. When stratified by race and stroke subtype, this change was driven by a decrease in ischemic stroke incidence among whites, whereas ischemic stroke incidence in blacks was unchanged. Hemorrhagic stroke incidence was unchanged in both races. For the first time, we report a significant decrease in stroke incidence within our population, which is consistent with other reports in the literature. This decrease was found only among whites, which suggests a worsening of the racial disparity in stroke incidence.

  17. Stroke Incidence is Decreasing in Whites, but Not in Blacks: A Population-Based Estimate of Temporal Trends in Stroke Incidence from the Greater Cincinnati/Northern Kentucky Stroke Study

    PubMed Central

    Kleindorfer, Dawn; Khoury, Jane; Moomaw, Charles J.; Alwell, Kathleen; Woo, Daniel; Flaherty, Matthew L.; Khatri, Pooja; Adeoye, Opeolu; Ferioli, Simona; Broderick, Joseph P.; Kissela, Brett M.

    2010-01-01

    Context While other studies (in largely white populations) have found that stroke incidence declined during the 1990s, we previously reported that stroke incidence in our population (18% of which was black) did not change during that decade and that incidence rates in blacks were significantly higher than in whites. We sought to update temporal trends in stroke incidence by adding new data obtained from our large, bi-racial population in 2005. Objective To examine temporal trends in stroke incidence and case fatality within a large, biracial population over time, by comparing stroke incidence rates from 1993/94, 1999, and 2005. Design, Setting, and Participants Within the Greater Cincinnati/Northern Kentucky population of 1.3 million, all strokes among area residents were ascertained at all local hospitals during 7/93-6/94 and calendar years 1999 and 2005. A sampling scheme was used to ascertain cases in the out-of-hospital setting. Only first-ever strokes were included in this analysis. Race-specific incidence rates, standardized to the 2000 U.S. Census population, and case-fatality rates were calculated. Results The number of physician-confirmed first-ever strokes in patients ≥20 years of age was 1,942 in 1993/94, 2,041 in 1999, and 1,921 in 2005. In all study periods, blacks had higher stroke incidence than whites, and case fatality rates were similar between races. In contrast to previous study periods, we found a significant decrease in overall stroke incidence in 2005. When stratified by race and stroke subtype, this change was driven by a decrease in ischemic stroke incidence among whites, while ischemic stroke incidence in blacks was unchanged. Hemorrhagic stroke incidence was unchanged in both races. Discussion For the first time, we report a significant decrease in stroke incidence within our population, which is consistent with other reports in the literature. This decrease was found only among whites, which suggests a worsening of the racial disparity in stroke incidence. PMID:20489177

  18. Association between glutathione S-transferase P1 Ile (105) Val gene polymorphism and chronic obstructive pulmonary disease: A meta-analysis based on seventeen case–control studies

    PubMed Central

    Yang, Lingjing; Li, Xixia; Tong, Xiang; Fan, Hong

    2015-01-01

    Introduction Previous studies have shown that glutathione S-transferase P1 (GSTP1) was associated with chronic obstructive pulmonary disease (COPD). However, the association between GSTP1 Ile (105) Val gene polymorphism and COPD remains controversial. To drive a more precise estimation, we performed a meta-analysis based on published case–control studies. Methods An electronic search of PubMed, EMBASE, Cochrane library, Web of Science and China Knowledge Resource Integrated (CNKI) Database for papers on GSTP1 Ile (105) Val gene polymorphism and COPD risk was performed. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygote model, heterozygote model, dominant model, recessive model and an additive mode. Statistical heterogeneity, test of publication bias and sensitivity analysis was performed. The software STATA (Version 13.0) was used data analysis. Results Overall, seventeen studies with 1892 cases and 2012 controls were included in this meta-analysis. The GSTP1 Ile (105) Val polymorphism showed pooled odds ratios for the homozygote comparison (OR = 1.501, 95%CI [0.862, 2.614]), heterozygote comparison (OR = 0.924, 95%CI [0.733, 1.165]), dominant model (OR = 1.003, 95%CI [0.756, 1.331]), recessive model (OR = 1.510, 95%CI [0.934, 2.439]), and an additive model (OR = 1.072, 95%CI [0.822, 1.398]). Conclusions In conclusion, the current meta-analysis, based on the most updated information, showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in any genetic models. The results of subgroup analysis also showed no significant association between GSTP1 Ile (105) Val gene polymorphism and COPD risk in Asian population and Caucasian population. Further studies involving large populations and careful control with age, sex, ethnicity, and cigarette smoking are greatly needed. PMID:26504746

  19. Socioeconomic inequalities in risk of hospitalization for community-acquired bacteremia: a Danish population-based case-control study.

    PubMed

    Koch, Kristoffer; Søgaard, Mette; Nørgaard, Mette; Thomsen, Reimar Wernich; Schønheyder, Henrik Carl

    2014-05-01

    In a Danish population-based case-control study, we examined the association between socioeconomic status (SES) and risk of community-acquired bacteremia, as well as the contribution of chronic diseases and substance abuse to differences in bacteremia risk. Analyses were based on 4,117 patients aged 30-65 years who were hospitalized with first-time community-acquired bacteremia during 2000-2008 and 41,170 population controls matched by sex, age, and region of residence. Individual-level information on SES (education and income), chronic diseases, and substance abuse was retrieved from public and medical registries. Conditional logistic regression was used to compute odds ratios for bacteremia. Persons of low SES had a substantially higher risk of bacteremia than those of high SES (for short duration of education vs. long duration, odds ratio = 2.30 (95% confidence interval: 2.10, 2.52); for low income vs. high income, odds ratio = 2.77 (95% confidence interval: 2.54, 3.02)). A higher prevalence of chronic diseases and substance abuse in low-SES individuals versus high-SES individuals explained 43%-48% of the socioeconomic differences in bacteremia risk. In a country with a universal welfare system, differences in the burden of chronic diseases and substance abuse seem to have major importance in explaining inequalities in bacteremia risk.

  20. Modelling the role of dietary habits and eating behaviours on the development of acute coronary syndrome or stroke: aims, design, and validation properties of a case-control study.

    PubMed

    Kastorini, Christina-Maria; Milionis, Haralampos J; Goudevenos, John A; Panagiotakos, Demosthenes B

    2010-09-14

    In this paper the methodology and procedures of a case-control study that will be developed for assessing the role of dietary habits and eating behaviours on the development of acute coronary syndrome and stroke is presented. Based on statistical power calculations, 1000 participants will be enrolled; of them, 250 will be consecutive patients with a first acute coronary event, 250 consecutive patients with a first ischaemic stroke, and 500 population-based healthy subjects (controls), age and sex matched to the cases. Socio-demographic, clinical, dietary, psychological, and other lifestyle characteristics will be measured. Dietary habits and eating behaviours will be evaluated with a special questionnaire that has been developed for the study.

  1. Refining and validating a two-stage and web-based cancer risk assessment tool for village doctors in China.

    PubMed

    Shen, Xing-Rong; Chai, Jing; Feng, Rui; Liu, Tong-Zhu; Tong, Gui-Xian; Cheng, Jing; Li, Kai-Chun; Xie, Shao-Yu; Shi, Yong; Wang, De-Bin

    2014-01-01

    The big gap between efficacy of population level prevention and expectations due to heterogeneity and complexity of cancer etiologic factors calls for selective yet personalized interventions based on effective risk assessment. This paper documents our research protocol aimed at refining and validating a two-stage and web- based cancer risk assessment tool, from a tentative one in use by an ongoing project, capable of identifying individuals at elevated risk for one or more types of the 80% leading cancers in rural China with adequate sensitivity and specificity and featuring low cost, easy application and cultural and technical sensitivity for farmers and village doctors. The protocol adopted a modified population-based case control design using 72, 000 non-patients as controls, 2, 200 cancer patients as cases, and another 600 patients as cases for external validation. Factors taken into account comprised 8 domains including diet and nutrition, risk behaviors, family history, precancerous diseases, related medical procedures, exposure to environment hazards, mood and feelings, physical activities and anthropologic and biologic factors. Modeling stresses explored various methodologies like empirical analysis, logistic regression, neuro-network analysis, decision theory and both internal and external validation using concordance statistics, predictive values, etc..

  2. Retinopathy of prematurity: a global perspective of the epidemics, population of babies at risk and implications for control.

    PubMed

    Gilbert, Clare

    2008-02-01

    Globally at least 50,000 children are blind from retinopathy of prematurity (ROP) which is now a significant cause of blindness in many middle income countries in Latin American and Eastern Europe. Retinopathy of prematurity is also being reported from the emerging economies of India and China. The characteristics of babies developing severe disease varies, with babies in middle and low income countries having a much wider range of birth weights and gestational ages than is currently the case in industrialized countries. Rates of disease requiring treatment also tend to be higher in middle and low income countries suggesting that babies are being exposed to risk factors which are, to a large extent, being controlled in industrialised countries. The reasons for this "third epidemic" of ROP are discussed as well as strategies for control, including the need for locally relevant, evidence based criteria which ensure that all babies at risk are examined.

  3. Association between Diabetes and Risk of Aortic Dissection: A Case-Control Study in a Chinese Population.

    PubMed

    He, Xingwei; Liu, Xintian; Liu, Wanjun; Wang, Bei; Liu, Yujian; Li, Zhuxi; Wang, Tao; Tan, Rong; Gao, Bo; Zeng, Hesong

    2015-01-01

    It is well-recognized that diabetes represents a powerful independent risk factor for cardiovascular diseases. However, very few studies have investigated the relationship between diabetes and risk of aortic dissection (AD). The aim of this case-control study was to evaluate the association between diabetes and risk of AD in Chinese population. A hospital-based case-control study, consisting of 2160 AD patients and 4320 controls, was conducted in a Chinese population. Demographic, clinical characteristics and risk factors were collected. Diabetes rate of patients with overall AD, Stanford type A AD and type B AD group was compared with that of corresponding matched control groups. Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) for relationship between diabetes and AD risk. The prevalence of diabetes was lower in AD cases than that of control subjects, whether it is the overall AD, type A AD or type B AD group (4.7% vs. 10.0%, 2.9% vs. 8.8%, 5.9% vs. 10.9%, all P<0.001). Furthermore, in multivariate model, diabetes was found to be associated with lower AD risk, which not only applies to the overall AD (OR = 0.2, 95%CI: 0.15-0.26), but also type A AD (OR = 0.12, 95% CI: 0.07-0.20) and type B AD (OR = 0.25, 95%CI: 0.18-0.33). We observed the paradoxical inverse relationship between DM and risk of AD in the Chinese population. These results suggest diabetes may play a protective role in the development of AD. However, further studies are needed to enrich related evidence, especially with regard to underlying mechanisms for these trends.

  4. Population-based programs for increasing colorectal cancer screening in the United States.

    PubMed

    Verma, Manisha; Sarfaty, Mona; Brooks, Durado; Wender, Richard C

    2015-01-01

    Answer questions and earn CME/CNE Screening to detect polyps or cancer at an early stage has been shown to produce better outcomes in colorectal cancer (CRC). Programs with a population-based approach can reach a large majority of the eligible population and can offer cost-effective interventions with the potential benefit of maximizing early cancer detection and prevention using a complete follow-up plan. The purpose of this review was to summarize the key features of population-based programs to increase CRC screening in the United States. A search was conducted in the SCOPUS, OvidSP, and PubMed databases. The authors selected published reports of population-based programs that met at least 5 of the 6 International Agency for Research on Cancer (IARC) criteria for cancer prevention and were known to the National Colorectal Cancer Roundtable. Interventions at the level of individual practices were not included in this review. IARC cancer prevention criteria served as a framework to assess the effective processes and elements of a population-based program. Eight programs were included in this review. Half of the programs met all IARC criteria, and all programs led to improvements in screening rates. The rate of colonoscopy after a positive stool test was heterogeneous among programs. Different population-based strategies were used to promote these screening programs, including system-based, provider-based, patient-based, and media-based strategies. Treatment of identified cancer cases was not included explicitly in 4 programs but was offered through routine medical care. Evidence-based methods for promoting CRC screening at a population level can guide the development of future approaches in health care prevention. The key elements of a successful population-based approach include adherence to the 6 IARC criteria and 4 additional elements (an identified external funding source, a structured policy for positive fecal occult blood test results and confirmed cancer cases, outreach activities for recruitment and patient education, and an established rescreening process). © 2015 American Cancer Society.

  5. Field-based high throughput phenotyping rapidly identifies genomic regions controlling yield components in rice

    PubMed Central

    Tanger, Paul; Klassen, Stephen; Mojica, Julius P.; Lovell, John T.; Moyers, Brook T.; Baraoidan, Marietta; Naredo, Maria Elizabeth B.; McNally, Kenneth L.; Poland, Jesse; Bush, Daniel R.; Leung, Hei; Leach, Jan E.; McKay, John K.

    2017-01-01

    To ensure food security in the face of population growth, decreasing water and land for agriculture, and increasing climate variability, crop yields must increase faster than the current rates. Increased yields will require implementing novel approaches in genetic discovery and breeding. Here we demonstrate the potential of field-based high throughput phenotyping (HTP) on a large recombinant population of rice to identify genetic variation underlying important traits. We find that detecting quantitative trait loci (QTL) with HTP phenotyping is as accurate and effective as traditional labor-intensive measures of flowering time, height, biomass, grain yield, and harvest index. Genetic mapping in this population, derived from a cross of an modern cultivar (IR64) with a landrace (Aswina), identified four alleles with negative effect on grain yield that are fixed in IR64, demonstrating the potential for HTP of large populations as a strategy for the second green revolution. PMID:28220807

  6. Sources of heterogeneity in case-control studies on associations between statins, ACE-inhibitors, and proton pump inhibitors and risk of pneumonia.

    PubMed

    de Groot, Mark C H; Klungel, Olaf H; Leufkens, Hubert G M; van Dijk, Liset; Grobbee, Diederick E; van de Garde, Ewoudt M W

    2014-10-01

    The heterogeneity in case-control studies on the associations between community-acquired pneumonia (CAP) and ACE-inhibitors (ACEi), statins, and proton pump inhibitors (PPI) hampers translation to clinical practice. Our objective is to explore sources of this heterogeneity by applying a common protocol in different data settings. We conducted ten case-control studies using data from five different health care databases. Databases varied on type of patients (hospitalised vs. GP), level of case validity, and mode of exposure ascertainment (prescription or dispensing based). Identified CAP patients and controls were matched on age, gender, and calendar year. Conditional logistic regression was used to calculate odds ratios (OR) for the associations between the drugs of interest and CAP. Associations were adjusted by a common set of potential confounders. Data of 38,742 cases and 118,019 controls were studied. Comparable patterns of variation between case-control studies were observed for ACEi, statins and PPI use and pneumonia risk with adjusted ORs varying from 1.04 to 1.49, 0.82 to 1.50 and 1.16 to 2.71, respectively. Overall, higher ORs were found for hospitalised CAP patients matched to population controls versus GP CAP patients matched to population controls. Prevalence of drug exposure was higher in dispensing data versus prescription data. We show that case-control selection and methods of exposure ascertainment induce bias that cannot be adjusted for and to a considerable extent explain the heterogeneity in results obtained in case-control studies on statins, ACEi and PPIs and CAP. The common protocol approach helps to better understand sources of variation in observational studies.

  7. Occupational UV-Exposure is a Major Risk Factor for Basal Cell Carcinoma: Results of the Population-Based Case-Control Study FB-181.

    PubMed

    Schmitt, Jochen; Haufe, Eva; Trautmann, Freya; Schulze, Hans-Joachim; Elsner, Peter; Drexler, Hans; Bauer, Andrea; Letzel, Stephan; John, Swen Malte; Fartasch, Manigé; Brüning, Thomas; Seidler, Andreas; Dugas-Breit, Susanne; Gina, Michal; Weistenhöfer, Wobbeke; Bachmann, Klaus; Bruhn, Ilka; Lang, Berenice Mareen; Bonness, Sonja; Allam, Jean Pierre; Grobe, William; Stange, Thoralf; Westerhausen, Stephan; Knuschke, Peter; Wittlich, Marc; Diepgen, Thomas Ludwig

    2018-01-01

    The aim of this study was to investigate the role of occupational and nonoccupational ultraviolet (UV)-exposure concerning the development of basal cell carcinoma (BCC). We undertook a population-based multicenter case-control study. Patients with first incident BCC (n = 836) were propensity score matched by age and sex to controls without skin cancer (n = 836). Sociodemographic characteristics, clinical characteristics, and lifetime UV-exposure were assessed by trained investigators. The differential estimation of occupational and nonoccupational UV-exposure dosages was based on validated instruments and established reference values. Associations were assessed using multivariable-adjusted conditional logistic regression models. Individuals with high levels of occupational UV-exposure were at significantly increased BCC-risk compared with individuals with low [odds ratio (OR) 1.84; 95% confidence interval (95% CI) 1.19 to 2.83 and moderate (OR 1.97; 95% CI 1.20 to 3.22) occupational UV-exposure. Nonoccupational UV-exposure was not independently associated with BCC. Skin cancer prevention strategies should be expanded to the occupational setting.

  8. A Century Spent Combating Rabies in Morocco (1911-2015): How Much Longer?

    PubMed

    Darkaoui, Sami; Cliquet, Florence; Wasniewski, Marine; Robardet, Emmanuelle; Aboulfidaa, Nadia; Bouslikhane, Mohammed; Fassi-Fihri, Ouafaa

    2017-01-01

    Rabies has no known beginning in Morocco and to date, government control efforts and plans fail to eradicate the disease. A review and analysis of available epidemiological data are crucial to learn lessons from the past and to propose effective actions. Legally, animal rabies is a notifiable disease since 1913 and legislation has been updated periodically since. Dogs have always been considered as both the disease's vector and reservoir, while cattle, other herbivores, and humans are victims. Animal rabies cases evolution from 1942 to 2015 is characterized by ascending phase then decreasing one following structured rabies control plan implementation in 1980s. Indeed, from 1986 to 2010, three rabies control plans have been conducted based on free of charge rabies vaccination of owned dogs through mass campaigns. The geographical distribution of rabies is stable over the years with highest cases number in rich rural areas and around cities. Human rabies cases are decreasing over the time (1976-2015) thanks to the opening of new antirabic treatment centers in the last decade which permit the administration of more PEPs. After a century of rabies control, Morocco registered an average of 301 animal cases and 21 human cases annually for the last decade (2005-2015). Few reasons led to those limited results. The lack in law enforcement and, moreover, the fact that the law do not take into account responsible dog ownership aspect are of importance. Lack of dog population knowledge and management and intersectoral coordination deficiency are additional failure reasons. The gathered data will help to build a new strategy with a focus on a "One Health" approach. Dog population ecology parameters' study is of primary importance. We estimated dog population to be 2.8 million dogs based on human:dog ratio. Enhancing vaccination coverage of dog population is feasible by combining parenteral vaccination and complementary oral vaccination. Updating legislation by inclusion of responsible dog ownership and law enforcement are crucial. Over the last century, Morocco registered a slow decreasing tendency in the number of animal and human rabies cases. Urgent strategy need to be implemented because rabies elimination is an achievable goal in Morocco.

  9. A Century Spent Combating Rabies in Morocco (1911–2015): How Much Longer?

    PubMed Central

    Darkaoui, Sami; Cliquet, Florence; Wasniewski, Marine; Robardet, Emmanuelle; Aboulfidaa, Nadia; Bouslikhane, Mohammed; Fassi-Fihri, Ouafaa

    2017-01-01

    Rabies has no known beginning in Morocco and to date, government control efforts and plans fail to eradicate the disease. A review and analysis of available epidemiological data are crucial to learn lessons from the past and to propose effective actions. Legally, animal rabies is a notifiable disease since 1913 and legislation has been updated periodically since. Dogs have always been considered as both the disease’s vector and reservoir, while cattle, other herbivores, and humans are victims. Animal rabies cases evolution from 1942 to 2015 is characterized by ascending phase then decreasing one following structured rabies control plan implementation in 1980s. Indeed, from 1986 to 2010, three rabies control plans have been conducted based on free of charge rabies vaccination of owned dogs through mass campaigns. The geographical distribution of rabies is stable over the years with highest cases number in rich rural areas and around cities. Human rabies cases are decreasing over the time (1976–2015) thanks to the opening of new antirabic treatment centers in the last decade which permit the administration of more PEPs. After a century of rabies control, Morocco registered an average of 301 animal cases and 21 human cases annually for the last decade (2005–2015). Few reasons led to those limited results. The lack in law enforcement and, moreover, the fact that the law do not take into account responsible dog ownership aspect are of importance. Lack of dog population knowledge and management and intersectoral coordination deficiency are additional failure reasons. The gathered data will help to build a new strategy with a focus on a “One Health” approach. Dog population ecology parameters’ study is of primary importance. We estimated dog population to be 2.8 million dogs based on human:dog ratio. Enhancing vaccination coverage of dog population is feasible by combining parenteral vaccination and complementary oral vaccination. Updating legislation by inclusion of responsible dog ownership and law enforcement are crucial. Over the last century, Morocco registered a slow decreasing tendency in the number of animal and human rabies cases. Urgent strategy need to be implemented because rabies elimination is an achievable goal in Morocco. PMID:28626749

  10. Mobile phone base stations and early childhood cancers: case-control study.

    PubMed

    Elliott, Paul; Toledano, Mireille B; Bennett, J; Beale, L; de Hoogh, K; Best, N; Briggs, D J

    2010-06-22

    To investigate the risk of early childhood cancers associated with the mother's exposure to radiofrequency from and proximity to macrocell mobile phone base stations (masts) during pregnancy. Case-control study. Cancer registry and national birth register data in Great Britain. 1397 cases of cancer in children aged 0-4 from national cancer registry 1999-2001 and 5588 birth controls from national birth register, individually matched by sex and date of birth (four controls per case). Incidence of cancers of the brain and central nervous system, leukaemia, and non-Hodgkin's lymphomas, and all cancers combined, adjusted for small area measures of education level, socioeconomic deprivation, population density, and population mixing. Mean distance of registered address at birth from a macrocell base station, based on a national database of 76,890 base station antennas in 1996-2001, was similar for cases and controls (1107 (SD 1131) m v 1073 (SD 1130) m, P=0.31), as was total power output of base stations within 700 m of the address (2.89 (SD 5.9) kW v 3.00 (SD 6.0) kW, P=0.54) and modelled power density (-30.3 (SD 21.7) dBm v -29.7 (SD 21.5) dBm, P=0.41). For modelled power density at the address at birth, compared with the lowest exposure category the adjusted odds ratios were 1.01 (95% confidence interval 0.87 to 1.18) in the intermediate and 1.02 (0.88 to 1.20) in the highest exposure category for all cancers (P=0.79 for trend), 0.97 (0.69 to 1.37) and 0.76 (0.51 to 1.12), respectively, for brain and central nervous system cancers (P=0.33 for trend), and 1.16 (0.90 to 1.48) and 1.03 (0.79 to 1.34) for leukaemia and non-Hodgkin's lymphoma (P=0.51 for trend). There is no association between risk of early childhood cancers and estimates of the mother's exposure to mobile phone base stations during pregnancy.

  11. Mobile phone base stations and early childhood cancers: case-control study

    PubMed Central

    Toledano, Mireille B; Bennett, J; Beale, L; de Hoogh, K; Best, N; Briggs, D J

    2010-01-01

    Objective To investigate the risk of early childhood cancers associated with the mother’s exposure to radiofrequency from and proximity to macrocell mobile phone base stations (masts) during pregnancy. Design Case-control study. Setting Cancer registry and national birth register data in Great Britain. Participants 1397 cases of cancer in children aged 0-4 from national cancer registry 1999-2001 and 5588 birth controls from national birth register, individually matched by sex and date of birth (four controls per case). Main outcome measures Incidence of cancers of the brain and central nervous system, leukaemia, and non-Hodgkin’s lymphomas, and all cancers combined, adjusted for small area measures of education level, socioeconomic deprivation, population density, and population mixing. Results Mean distance of registered address at birth from a macrocell base station, based on a national database of 76 890 base station antennas in 1996-2001, was similar for cases and controls (1107 (SD 1131) m v 1073 (SD 1130) m, P=0.31), as was total power output of base stations within 700 m of the address (2.89 (SD 5.9) kW v 3.00 (SD 6.0) kW, P=0.54) and modelled power density (−30.3 (SD 21.7) dBm v −29.7 (SD 21.5) dBm, P=0.41). For modelled power density at the address at birth, compared with the lowest exposure category the adjusted odds ratios were 1.01 (95% confidence interval 0.87 to 1.18) in the intermediate and 1.02 (0.88 to 1.20) in the highest exposure category for all cancers (P=0.79 for trend), 0.97 (0.69 to 1.37) and 0.76 (0.51 to 1.12), respectively, for brain and central nervous system cancers (P=0.33 for trend), and 1.16 (0.90 to 1.48) and 1.03 (0.79 to 1.34) for leukaemia and non-Hodgkin’s lymphoma (P=0.51 for trend). Conclusions There is no association between risk of early childhood cancers and estimates of the mother’s exposure to mobile phone base stations during pregnancy. PMID:20570865

  12. The balancing act: experts' opinions about the relative resourcing of tobacco control efforts for the general population versus disadvantaged populations.

    PubMed

    Paul, Christine Louise; Bonevski, Billie; Turon, Heidi Erin; Bryant, Jamie

    2012-07-01

    Despite the persistent socioeconomic gradient associated with smoking, little is known about how to 'close the gap'. There is a debate regarding the implications of directing resources away from general population efforts towards disadvantaged groups. The study explored views of those with expertise in tobacco control about the appropriate balance of tobacco control resourcing between the general population and disadvantaged groups. A Web-based survey of 192 respondents (response rate 65%) working in tobacco control in Australia and New Zealand was completed. Respondents were sampled from the Australian and New Zealand Tobacco Control Contact List and a literature search. Respondents were asked to allocate a hypothetical budget for: (a) anti-tobacco mass media campaigns; and (b) tobacco control research. The vast majority (93%) of respondents believed that some tobacco control resources should be specifically directed towards disadvantaged groups. Respondents believed up to half of mass media resources should be directed towards disadvantaged groups. In the case of tobacco control research, the median allocation to the general population was approximately one-third of a hypothetical research budget. It appears there is a desire among the Australian and New Zealand tobacco control community for substantial effort to be directed towards disadvantaged groups. It is important to develop an evidence base to ensure an efficient and equitable approach to balancing the potentially competing demands of general population versus disadvantaged group activities in relation to tobacco control. © 2012 Australasian Professional Society on Alcohol and other Drugs.

  13. Oral health in patients treated by positive airway pressure for obstructive sleep apnea: a population-based case-control study.

    PubMed

    Carra, M C; Thomas, F; Schmitt, A; Pannier, B; Danchin, N; Bouchard, Ph

    2016-03-01

    Recent epidemiological evidence suggests that patients with obstructive sleep apnea (OSA) have an increased risk of periodontal disease. Little is known about the oral health of OSA patients treated by continuous or bi-level positive airway pressure (CPAP/BiPAP). The aim of this population-based case-control study was to compare oral health variables (amount of plaque, calculus, gingival inflammation, and masticatory function) between CPAP/BiPAP users and control subjects. The study population was retrieved from a French cohort examined between 2012 and 2013 at the Centre d'Investigations Préventives et Cliniques of Paris. Cases were selected if they reported to be treated by CPAP/BiPAP; controls were age-, gender-, and BMI-matched based on a 1:2 ratio. Univariate and logistic regression analyses were performed for group comparisons. Over a total of 20,436 subjects, 287 CPAP/BiPAP users (mean age (SD) 57.6 years (11.5); 76.3 % males) who underwent medical and dental examinations were compared with 574 matched controls (no OSA, no CPAP/BiPAP). CPAP/BiPAP users reported significantly higher prevalence of diabetes (15.6 vs. 10.3 %; p = 0.012; odds ratio (OR) 1.68), history of hypertension (36.5 vs. 26.1 %; p = 0.003; OR 1.62), cardiovascular diseases (14.1 vs. 8.8 %; p = 0.029; OR 1.69), and sleep complaints (59 vs. 34.4 %; p = 0.0001; OR 2.75). CPAP/BiPAP users also showed higher levels of depression and stress compared to controls. However, no group difference was observed for the amount of dental plaque, calculus, gingival inflammation, and masticatory function. Oral health of OSA patients treated by CPAP/BiPAP is comparable to that of matched controls in terms of amount of plaque, gingival inflammation, and masticatory function.

  14. Utilizing population controls in rare-variant case-parent association tests.

    PubMed

    Jiang, Yu; Satten, Glen A; Han, Yujun; Epstein, Michael P; Heinzen, Erin L; Goldstein, David B; Allen, Andrew S

    2014-06-05

    There is great interest in detecting associations between human traits and rare genetic variation. To address the low power implicit in single-locus tests of rare genetic variants, many rare-variant association approaches attempt to accumulate information across a gene, often by taking linear combinations of single-locus contributions to a statistic. Using the right linear combination is key-an optimal test will up-weight true causal variants, down-weight neutral variants, and correctly assign the direction of effect for causal variants. Here, we propose a procedure that exploits data from population controls to estimate the linear combination to be used in an case-parent trio rare-variant association test. Specifically, we estimate the linear combination by comparing population control allele frequencies with allele frequencies in the parents of affected offspring. These estimates are then used to construct a rare-variant transmission disequilibrium test (rvTDT) in the case-parent data. Because the rvTDT is conditional on the parents' data, using parental data in estimating the linear combination does not affect the validity or asymptotic distribution of the rvTDT. By using simulation, we show that our new population-control-based rvTDT can dramatically improve power over rvTDTs that do not use population control information across a wide variety of genetic architectures. It also remains valid under population stratification. We apply the approach to a cohort of epileptic encephalopathy (EE) trios and find that dominant (or additive) inherited rare variants are unlikely to play a substantial role within EE genes previously identified through de novo mutation studies. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  15. Population-level approaches to universal health coverage in resource-poor settings: lessons from tobacco control policy in Vietnam.

    PubMed

    Higashi, Hideki; Khuong, Tuan A; Ngo, Anh D; Hill, Peter S

    2011-07-01

    Population-based health promotion and disease prevention approaches are essential elements in achieving universal health coverage; yet they frequently do not appear on national policy agendas. This paper suggests that resource-poor countries should take greater advantage of such approaches to reach all segments of the population to positively affect health outcomes and equity, especially considering the epidemic of chronic non-communicable diseases and associated modifiable risk factors. Tobacco control policy development and implementation in Vietnam provides a case study to discuss opportunities and challenges associated with such strategies.

  16. Three ADIPOR1 Polymorphisms and Cancer Risk: A Meta-Analysis of Case-Control Studies.

    PubMed

    Ye, Jiaxiang; Jiang, Li; Wu, Changliang; Liu, Aiqun; Mao, Sufei; Ge, Lianying

    2015-01-01

    Studies have come to conflicting conclusions about whether polymorphisms in the adiponectin receptor 1 gene (ADIPOR1) are associated with cancer risk. To help resolve this question, we meta-analyzed case-control studies in the literature. PubMed, EMBASE, Cochrane Library, the Chinese Biological Medical Database and the Chinese National Knowledge Infrastructure Database were systematically searched to identify all case-control studies published through February 2015 examining any ADIPOR1 polymorphisms and risk of any type of cancer. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. A total of 13 case-control studies involving 5,750 cases and 6,762 controls were analyzed. Analysis of the entire study population revealed a significant association between rs1342387(G/A) and overall cancer risk using a homozygous model (OR 0.82, 95%CI 0.72 to 0.94), heterozygous model (OR 0.84, 95%CI 0.76 to 0.93), dominant model (OR 0.85, 95%CI 0.75 to 0.97) and allele contrast model (OR 0.88, 95%CI 0.80 to 0.97). However, subgroup analysis showed that this association was significant only for Asians in the case of colorectal cancer. No significant associations were found between rs12733285(C/T) or rs7539542(C/G) and cancer risk, either in analyses of the entire study population or in analyses of subgroups. Our meta-analysis suggests that the ADIPOR1 rs1342387(G/A) polymorphism, but not rs12733285(C/T) or rs7539542(C/G), may be associated with cancer risk, especially risk of colorectal cancer in Asians. Large, well-designed studies are needed to verify our findings.

  17. Birth order and Risk of Childhood Cancer: A Pooled Analysis from Five U.S. States

    PubMed Central

    Von Behren, Julie; Spector, Logan G.; Mueller, Beth A.; Carozza, Susan E.; Chow, Eric J.; Fox, Erin E.; Horel, Scott; Johnson, Kimberly J.; McLaughlin, Colleen; Puumala, Susan E.; Ross, Julie A.; Reynolds, Peggy

    2010-01-01

    The causes of childhood cancers are largely unknown. Birth order has been used as a proxy for prenatal and postnatal exposures, such as frequency of infections and in utero hormone exposures. We investigated the association between birth order and childhood cancers in a pooled case-control dataset. The subjects were drawn from population-based registries of cancers and births in California, Minnesota, New York, Texas, and Washington. We included 17,672 cases less than 15 years of age who were diagnosed from1980-2004 and 57,966 randomly selected controls born 1970-2004, excluding children with Down syndrome. We calculated odds ratios and 95% confidence intervals using logistic regression, adjusted for sex, birth year, maternal race, maternal age, multiple birth, gestational age, and birth weight. Overall, we found an inverse relationship between childhood cancer risk and birth order. For children in the fourth or higher birth order category compared to first-born children, the adjusted OR was 0.87 (95% CI: 0.81, 0.93) for all cancers combined. When we examined risks by cancer type, a decreasing risk with increasing birth order was seen in the central nervous system (CNS) tumors, neuroblastoma, bilateral retinoblastoma, Wilms tumor, and rhabdomyosarcoma. We observed increased risks with increasing birth order for acute myeloid leukemia but a slight decrease in risk for acute lymphoid leukemia. These risk estimates were based on a very large sample size which allowed us to examine rare cancer types with greater statistical power than in most previous studies, however the biologic mechanisms remain to be elucidated. PMID:20715170

  18. Lack of replication of previous autism spectrum disorder GWAS hits in European populations.

    PubMed

    Torrico, Bàrbara; Chiocchetti, Andreas G; Bacchelli, Elena; Trabetti, Elisabetta; Hervás, Amaia; Franke, Barbara; Buitelaar, Jan K; Rommelse, Nanda; Yousaf, Afsheen; Duketis, Eftichia; Freitag, Christine M; Caballero-Andaluz, Rafaela; Martinez-Mir, Amalia; Scholl, Francisco G; Ribasés, Marta; Battaglia, Agatino; Malerba, Giovanni; Delorme, Richard; Benabou, Marion; Maestrini, Elena; Bourgeron, Thomas; Cormand, Bru; Toma, Claudio

    2017-02-01

    Common variants contribute significantly to the genetics of autism spectrum disorder (ASD), although the identification of individual risk polymorphisms remains still elusive due to their small effect sizes and limited sample sizes available for association studies. During the last decade several genome-wide association studies (GWAS) have enabled the detection of a few plausible risk variants. The three main studies are family-based and pointed at SEMA5A (rs10513025), MACROD2 (rs4141463) and MSNP1 (rs4307059). In our study we attempted to replicate these GWAS hits using a case-control association study in five European populations of ASD patients and gender-matched controls, all Caucasians. Results showed no association of individual variants with ASD in any of the population groups considered or in the combined European sample. We performed a meta-analysis study across five European populations for rs10513025 (1,904 ASD cases and 2,674 controls), seven European populations for rs4141463 (2,855 ASD cases and 36,177 controls) and five European populations for rs4307059 (2,347 ASD cases and 2,764 controls). The results showed an odds ratio (OR) of 1.05 (95% CI = 0.84-1.32) for rs10513025, 1.0002 (95% CI = 0.93-1.08) for rs4141463 and 1.01 (95% CI = 0.92-1.1) for rs4307059, with no significant P-values (rs10513025, P = 0.73; rs4141463, P = 0.95; rs4307059, P = 0.9). No association was found when we considered either only high functioning autism (HFA), genders separately or only multiplex families. Ongoing GWAS projects with larger ASD cohorts will contribute to clarify the role of common variation in the disorder and will likely identify risk variants of modest effect not detected previously. Autism Res 2017, 10: 202-211. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  19. Adjusting Expected Mortality Rates Using Information From a Control Population: An Example Using Socioeconomic Status.

    PubMed

    Bower, Hannah; Andersson, Therese M-L; Crowther, Michael J; Dickman, Paul W; Lambe, Mats; Lambert, Paul C

    2018-04-01

    Expected or reference mortality rates are commonly used in the calculation of measures such as relative survival in population-based cancer survival studies and standardized mortality ratios. These expected rates are usually presented according to age, sex, and calendar year. In certain situations, stratification of expected rates by other factors is required to avoid potential bias if interest lies in quantifying measures according to such factors as, for example, socioeconomic status. If data are not available on a population level, information from a control population could be used to adjust expected rates. We have presented two approaches for adjusting expected mortality rates using information from a control population: a Poisson generalized linear model and a flexible parametric survival model. We used a control group from BCBaSe-a register-based, matched breast cancer cohort in Sweden with diagnoses between 1992 and 2012-to illustrate the two methods using socioeconomic status as a risk factor of interest. Results showed that Poisson and flexible parametric survival approaches estimate similar adjusted mortality rates according to socioeconomic status. Additional uncertainty involved in the methods to estimate stratified, expected mortality rates described in this study can be accounted for using a parametric bootstrap, but this might make little difference if using a large control population.

  20. An exome-wide analysis of low frequency and rare variants in relation to risk of breast cancer in African American Women: the AMBER Consortium

    PubMed Central

    Haddad, Stephen A.; Ruiz-Narváez, Edward A.; Haiman, Christopher A.; Sucheston-Campbell, Lara E.; Bensen, Jeannette T.; Zhu, Qianqian; Liu, Song; Yao, Song; Bandera, Elisa V.; Rosenberg, Lynn; Olshan, Andrew F.; Ambrosone, Christine B.; Palmer, Julie R.; Lunetta, Kathryn L.

    2016-01-01

    A large percentage of breast cancer heritability remains unaccounted for, and most of the known susceptibility loci have been established in European and Asian populations. Rare variants may contribute to the unexplained heritability of this disease, including in women of African ancestry (AA). We conducted an exome-wide analysis of rare variants in relation to risk of overall and subtype-specific breast cancer in the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, which includes data from four large studies of AA women. Genotyping on the Illumina Human Exome Beadchip yielded data for 170 812 SNPs and 8287 subjects: 3629 cases (1093 estrogen receptor negative (ER−), 1968 ER+, 568 ER unknown) and 4658 controls, the largest exome chip study to date for AA breast cancer. Pooled gene-based association analyses were performed using the unified optimal sequence kernel association test (SKAT-O) for variants with minor allele frequency (MAF) ≤ 5%. In addition, each variant with MAF >0.5% was tested for association using logistic regression. There were no significant associations with overall breast cancer. However, a novel gene, FBXL22 (P = 8.2×10–6), and a gene previously identified in GWAS of European ancestry populations, PDE4D (P = 1.2×10–6), were significantly associated with ER− breast cancer after correction for multiple testing. Cases with the associated rare variants were also negative for progesterone and human epidermal growth factor receptors—thus, triple-negative cancer. Replication is required to confirm these gene-level associations, which are based on very small counts at extremely rare SNPs. PMID:27267999

  1. Medication Use in Pregnancy in Relation to the Risk of Isolated Clubfoot in Offspring

    PubMed Central

    Werler, Martha M.; Yazdy, Mahsa M.; Kasser, James R.; Mahan, Susan T.; Meyer, Robert E.; Anderka, Marlene; Druschel, Charlotte M.; Mitchell, Allen A.

    2014-01-01

    Clubfoot, a common major structural malformation, develops early in gestation. Epidemiologic studies have identified higher risks among boys, first-born children, and babies with a family history of clubfoot, but studies of risks associated with maternal exposures are lacking. We conducted the first large-scale, population-based, case-control study of clubfoot with detailed information on maternal medication use in pregnancy. Study subjects were ascertained from birth defect registries in Massachusetts, New York, and North Carolina during 2007–2011. Cases were 646 mothers of children with clubfoot without other major structural malformations (i.e., isolated clubfoot); controls were mothers of 2,037 children born without major malformations. Mothers were interviewed within 12 months of delivery about medication use, including product, timing, and frequency. Odds ratios were estimated for exposure to 27 medications in pregnancy months 2–4 after adjustment for study site, infant sex, first-born status, body mass index (weight (kg)/height (m)2), and smoking. Odds ratios were less than 1.20 for 14 of the medications; of the remainder, most odds ratios were only slightly elevated (range, 1.21–1.66), with wide confidence intervals. The use of antiviral drugs was more common in clubfoot cases than in controls (odds ratio = 4.22, 95% confidence interval: 1.52, 11.73). Most of these results are new findings and require confirmation in other studies. PMID:24824985

  2. Multicenter cohort association study of SLC2A1 single nucleotide polymorphisms and age-related macular degeneration

    PubMed Central

    Baas, Dominique C.; Ho, Lintje; Tanck, Michael W.T.; Fritsche, Lars G.; Merriam, Joanna E.; van het Slot, Ruben; Koeleman, Bobby P.C.; Gorgels, Theo G.M.F.; van Duijn, Cornelia M.; Uitterlinden, André G.; de Jong, Paulus T.V.M.; Hofman, Albert; ten Brink, Jacoline B.; Vingerling, Johannes R.; Klaver, Caroline C.W.; Dean, Michael; Weber, Bernhard H. F.; Allikmets, Rando; Hageman, Gregory S.

    2012-01-01

    Purpose Age-related macular degeneration (AMD) is a major cause of blindness in older adults and has a genetically complex background. This study examines the potential association between single nucleotide polymorphisms (SNPs) in the glucose transporter 1 (SLC2A1) gene and AMD. SLC2A1 regulates the bioavailability of glucose in the retinal pigment epithelium (RPE), which might influence oxidative stress–mediated AMD pathology. Methods Twenty-two SNPs spanning the SLC2A1 gene were genotyped in 375 cases and 199 controls from an initial discovery cohort (the Amsterdam-Rotterdam-Netherlands study). Replication testing was performed in The Rotterdam Study (the Netherlands) and study populations from Würzburg (Germany), the Age Related Eye Disease Study (AREDS; United States), Columbia University (United States), and Iowa University (United States). Subsequently, a meta-analysis of SNP association was performed. Results In the discovery cohort, significant genotypic association between three SNPs (rs3754219, rs4660687, and rs841853) and AMD was found. Replication in five large independent (Caucasian) cohorts (4,860 cases and 4,004 controls) did not yield consistent association results. The genotype frequencies for these SNPs were significantly different for the controls and/or cases among the six individual populations. Meta-analysis revealed significant heterogeneity of effect between the studies. Conclusions No overall association between SLC2A1 SNPs and AMD was demonstrated. Since the genotype frequencies for the three SLC2A1 SNPs were significantly different for the controls and/or cases between the six cohorts, this study corroborates previous evidence that population dependent genetic risk heterogeneity in AMD exists. PMID:22509097

  3. The MOBI-Kids Study Protocol: Challenges in Assessing Childhood and Adolescent Exposure to Electromagnetic Fields from Wireless Telecommunication Technologies and Possible Association with Brain Tumor Risk.

    PubMed

    Sadetzki, Siegal; Langer, Chelsea Eastman; Bruchim, Revital; Kundi, Michael; Merletti, Franco; Vermeulen, Roel; Kromhout, Hans; Lee, Ae-Kyoung; Maslanyj, Myron; Sim, Malcolm R; Taki, Masao; Wiart, Joe; Armstrong, Bruce; Milne, Elizabeth; Benke, Geza; Schattner, Rosa; Hutter, Hans-Peter; Woehrer, Adelheid; Krewski, Daniel; Mohipp, Charmaine; Momoli, Franco; Ritvo, Paul; Spinelli, John; Lacour, Brigitte; Delmas, Dominique; Remen, Thomas; Radon, Katja; Weinmann, Tobias; Klostermann, Swaantje; Heinrich, Sabine; Petridou, Eleni; Bouka, Evdoxia; Panagopoulou, Paraskevi; Dikshit, Rajesh; Nagrani, Rajini; Even-Nir, Hadas; Chetrit, Angela; Maule, Milena; Migliore, Enrica; Filippini, Graziella; Miligi, Lucia; Mattioli, Stefano; Yamaguchi, Naohito; Kojimahara, Noriko; Ha, Mina; Choi, Kyung-Hwa; Mannetje, Andrea 't; Eng, Amanda; Woodward, Alistair; Carretero, Gema; Alguacil, Juan; Aragones, Nuria; Suare-Varela, Maria Morales; Goedhart, Geertje; Schouten-van Meeteren, A Antoinette Y N; Reedijk, A Ardine M J; Cardis, Elisabeth

    2014-01-01

    The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case-control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10-24 years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people.

  4. COPS: Large-scale nonlinearly constrained optimization problems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bondarenko, A.S.; Bortz, D.M.; More, J.J.

    2000-02-10

    The authors have started the development of COPS, a collection of large-scale nonlinearly Constrained Optimization Problems. The primary purpose of this collection is to provide difficult test cases for optimization software. Problems in the current version of the collection come from fluid dynamics, population dynamics, optimal design, and optimal control. For each problem they provide a short description of the problem, notes on the formulation of the problem, and results of computational experiments with general optimization solvers. They currently have results for DONLP2, LANCELOT, MINOS, SNOPT, and LOQO.

  5. Islands in the sea: extreme female natal site fidelity in the Australian sea lion, Neophoca cinerea.

    PubMed

    Campbell, R A; Gales, N J; Lento, G M; Baker, C S

    2008-02-23

    Pinnipeds (seals, fur seals, sea lions and walrus) form large breeding aggregations with females often remaining faithful to a natal site or area. In these cases, females are philopatric to regional areas on broad geographical scales of hundreds to thousands of kilometers. An investigation of variation in a control region sequence of mtDNA in the Australian sea lion (Neophoca cinerea) has shown a case of extreme female natal site fidelity that has resulted in almost fixed population differentiation across its range (PhiST=0.93). This high level of population subdivision over short geographical distances (approx. 60 km) is unparalleled in any social marine mammal and reflects the unique life-history traits of this rare species. The high level of population subdivision and exclusive female natal site fidelity has important ramifications for conservation management, and poses many interesting questions of both academic and applied interest.

  6. Cardiovascular health status and metabolic syndrome in Ecuadorian natives/Mestizos aged 40 years or more with and without stroke and ischemic heart disease--an atahualpa project case-control nested study.

    PubMed

    Del Brutto, Oscar H; Mera, Robertino M; Montalván, Martha; Del Brutto, Victor J; Zambrano, Mauricio; Santamaría, Milton; Tettamanti, Daniel

    2014-04-01

    Knowledge of regional-specific cardiovascular risk factors is mandatory to reduce the growing burden of stroke and ischemic heart disease in Latin American populations. We conducted a population-based case-control study to assess which risk factors are associated with the occurrence of vascular events in natives/mestizos living in rural coastal Ecuador. We assessed the cardiovascular health (CVH) status and the presence of the metabolic syndrome in all Atahualpa residents aged 40 years or more with stroke and ischemic heart disease and in randomly selected healthy persons to evaluate differences in the prevalence of such risk factors between patients and controls. A total of 120 persons (24 with stroke or ischemic heart disease and 96 matched controls) were included. A poor CVH status (according to the American Heart Association) was found in 87.5% case-patients and 81.3% controls (P = .464). The metabolic syndrome was present in the same proportion (58.3%) of case-patients and controls. Likewise, both sets of risk factors (poor CVH status and the metabolic syndrome) were equally prevalent among both groups (58.3% versus 49%, P = .501). This case-control study suggests that none of the measured risk factors is associated with the occurrence of vascular events. It is possible that some yet unmeasured risk factors or an unknown genetic predisposition may account for a sizable proportion of stroke and ischemic heart disease occurring in the native/mestizo population of rural coastal Ecuador. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  7. The demand control model and circadian saliva cortisol variations in a Swedish population based sample (The PART study)

    PubMed Central

    Alderling, Magnus; Theorell, Töres; de la Torre, Bartolomé; Lundberg, Ingvar

    2006-01-01

    Background Previous studies of the relationship between job strain and blood or saliva cortisol levels have been small and based on selected occupational groups. Our aim was to examine the association between job strain and saliva cortisol levels in a population-based study in which a number of potential confounders could be adjusted for. Methods The material derives from a population-based study in Stockholm on mental health and its potential determinants. Two data collections were performed three years apart with more than 8500 subjects responding to a questionnaire in both waves. In this paper our analyses are based on 529 individuals who held a job, participated in both waves as well as in an interview linked to the second wave. They gave saliva samples at awakening, half an hour later, at lunchtime and before going to bed on a weekday in close connection with the interview. Job control and job demands were assessed from the questionnaire in the second wave. Mixed models were used to analyse the association between the demand control model and saliva cortisol. Results Women in low strain jobs (high control and low demands) had significantly lower cortisol levels half an hour after awakening than women in high strain (low control and high demands), active (high control and high demands) or passive jobs (low control and low demands). There were no significant differences between the groups during other parts of the day and furthermore there was no difference between the job strain, active and passive groups. For men, no differences were found between demand control groups. Conclusion This population-based study, on a relatively large sample, weakly support the hypothesis that the demand control model is associated with saliva cortisol concentrations. PMID:17129377

  8. Beta2-adrenergic agonist use and the risk of multiple sclerosis: a total population-based case-control study.

    PubMed

    Tsai, Ching-Piao; Lin, Feng-Cheng; Lee, Charles Tzu-Chi

    2014-10-01

    The aim of this study was to investigate whether the use of fenoterol, a beta2-adrenergic agonist, was associated with multiple sclerosis (MS) risk by conducting a total population-based case-control study in Taiwan. A total of 578 patients with newly diagnosed MS who had a severely disabling disease (SDD) certificate between January 1, 2002 and December 1, 2008 comprised the case group. These cases were compared with 2890 gender-, age-, residence-, and insurance premium-matched controls. Fenoterol use was analyzed using a conditional logistic regression model that controlled for asthma, chronic obstructive pulmonary disease (COPD), salbutamol and steroid use. Compared with the group of people who did not use fenoterol, the adjusted odds ratios were 0.67 (95% confidence interval (CI) = 0.48-0.93, p = 0.016) for the group prescribed fenoterol below 2.25 cumulative defined daily dose (cDDD) and 0.49 (95% CI = 0.33-0.71, p < 0.001) for the group with a cumulative fenoterol use of more than 2.25 cDDD. The dose-response relationship was similar within the non-asthma patients. The associations were similar between males and females, but differences between age groups were observed. The results of this study suggest that fenoterol use may reduce the risk of MS. © The Author(s), 2014.

  9. Maternal consumption of coffee and tea during pregnancy and risk of childhood brain tumors: results from an Australian case-control study.

    PubMed

    Greenop, Kathryn R; Miller, Margaret; Attia, John; Ashton, Lesley J; Cohn, Richard; Armstrong, Bruce K; Milne, Elizabeth

    2014-10-01

    The causes of childhood brain tumors (CBT) are largely unknown, but gestational diet may influence this risk. The aim of this analysis was to investigate whether maternal coffee or tea consumption during pregnancy was associated with the risk of CBT. The Australian Study of the Causes of Childhood Brain Tumours was a population-based, Australian case-control study conducted between 2005 and 2010. Case children were recruited from 10 pediatric oncology centers and control children by nationwide random-digit dialing, frequency matched to cases on the basis of age, sex and state of residence. Coffee and tea intake were assessed using a food frequency questionnaire. Data on coffee and tea consumption during pregnancy were available from 293 case mothers and 726 control mothers. Odds ratios (ORs) and confidence intervals (CIs) were calculated using multivariable unconditional logistic regression. There was little evidence of an association between gestational consumption of any coffee (OR 1.23, 95% CI 0.92, 1.64) or tea (OR 1.00, 95% CI 0.74, 1.36) and CBT risk. Among children aged under 5 years, the OR for any coffee consumption during pregnancy was 1.76 (95% CI 1.09, 2.84) and for ≥2 cups per day during pregnancy was 2.52 (95% CI 1.26, 5.04). There was little evidence that associations with coffee or tea intake differed by parental smoking status. These results suggest a positive association between coffee intake ≥2 cups per day and risk of CBT in younger children, although some estimates are imprecise. There was no association between maternal tea drinking and risk of CBT.

  10. Risk Factors for Stillbirth: Findings from a Population-Based Case-Control Study, Haryana, India.

    PubMed

    Neogi, Sutapa Bandyopadhyay; Negandhi, Preeti; Chopra, Sapna; Das, Ankan Mukherjee; Zodpey, Sanjay; Gupta, Ravi Kant; Gupta, Rakesh

    2016-01-01

    Stillbirth is a prevalent adverse outcome of pregnancy in India despite efforts to improve care of women during pregnancy. Risk factors for stillbirths include sociodemographic factors, medical complications during pregnancy, intake of harmful drugs, and complications during delivery. The objective of the study was to examine the risk factors for stillbirth with a focus on sex selection drugs (SSDs). A population-based case-control study was undertaken in Haryana. Cases of stillbirths were identified from the Maternal Infant Death Review System portal of Haryana state for the months of August-September 2014. A consecutive birth from the same geographical area as the case was selected as the control. The sample size was 325 per group. Mothers were interviewed using a validated tool. Bivariate analyses and logistic regression were conducted to examine the association between risk factors and stillbirth. Attributable risk proportions (ARP) and population attributable risk proportions (PARP) were estimated. The sociodemographic profiles of the cases and controls were similar. History of intake of SSDs [adjusted odds ratio (OR) 2.6, 95% confidence interval (CI) 1.5, 4.5] emerged as a risk factor. Other significant factors were preterm <37 weeks (OR 3.5, 95% CI 2.1, 6.0), history of previous stillbirths (OR 4.0, 95% CI 2.1, 7.8), and complications during labour (OR 3.3, 95% CI 2.1, 5.3). Estimates of the ARP and PARP for intake of SSDs were 0.60 (95% CI 0.32, 0.77) and 0.1 (95% CI -0.13, 0.28), respectively. SSDs could be attributed as a risk factor in a fifth of the cases of stillbirths. The number needed to harm for the use of SSDs in causing adverse effect of stillbirths was 5, suggesting thereby that for every five mothers exposed to SSDs, one would have stillbirth. Greater efforts are required to inform people about the harmful effects of SSD consumption during pregnancy. © 2015 John Wiley & Sons Ltd.

  11. Effect of Tubal Sterilization Technique on Risk of Serous Ovarian and Primary Peritoneal Carcinoma

    PubMed Central

    LESSARD-ANDERSON, Collette R.; HANDLOGTEN, Kathryn S.; MOLITOR, Rochelle J.; DOWDY, Sean C.; CLIBY, William A.; WEAVER, Amy L.; SAUVER, Jennifer ST.; BAKKUM-GAMEZ, Jamie N.

    2014-01-01

    Objective To determine the effect of excisional tubal sterilization on subsequent development of serous epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC). Methods We performed a population-based, nested case-control study using the Rochester Epidemiology Project. We identified all patients with a diagnosis of serous EOC or PPC from 1966 through 2009. Each case was age-matched to 2 controls without either diagnosis. Odds ratios (ORs) and corresponding 95% CIs were estimated from conditional logistic regression models. Models were adjusted for prior hysterectomy, prior salpingo-oophorectomy, oral contraceptive use, endometriosis, infertility, gravidity, and parity. Results In total, we identified 194 cases of serous EOC and PPC during the study period and matched them with 388 controls (mean [SD] age, 61.4 [15.2] years). Fourteen cases (7.2%) and 46 controls (11.9%) had undergone tubal sterilization. Adjusted risk of serous EOC or PPC was slightly lower after any tubal sterilization (OR, 0.59 [95% CI, 0.29–1.17]; P=.13). The rate of excisional tubal sterilization was lower in cases than controls (2.6% vs 6.4%). Adjusted risk of serous EOC and PPC was decreased by 64% after excisional tubal sterilization (OR, 0.36 [95% CI, 0.13–1.02]; P=.054) compared with those without sterilization or with nonexcisional tubal sterilization. Conclusions We present a population-based investigation of the effects of excisional tubal sterilization on the risk of serous EOC and PPC. Excisional methods may confer greater risk reduction than other sterilization methods. PMID:25316178

  12. A concordance index for matched case-control studies with applications in cancer risk.

    PubMed

    Brentnall, Adam R; Cuzick, Jack; Field, John; Duffy, Stephen W

    2015-02-10

    In unmatched case-control studies, the area under the receiver operating characteristic (ROC) curve (AUC) may be used to measure how well a variable discriminates between cases and controls. The AUC is sometimes used in matched case-control studies by ignoring matching, but it lacks interpretation because it is not based on an estimate of the ROC for the population of interest. We introduce an alternative measure of discrimination that is the concordance of risk factors conditional on the matching factors. Parametric and non-parametric estimators are given for different matching scenarios, and applied to real data from breast and lung cancer case-control studies. Diagnostic plots to verify the constancy of discrimination over matching factors are demonstrated. The proposed simple measure is easy to use, interpret, more efficient than unmatched AUC statistics and may be applied to compare the conditional discrimination performance of risk factors. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Prostate cancer, benign prostatic hyperplasia and physical activity in Shanghai, China.

    PubMed

    Lacey, J V; Deng, J; Dosemeci, M; Gao, Y T; Mostofi, F K; Sesterhenn, I A; Xie, T; Hsing, A W

    2001-04-01

    Studies suggest that increased levels of physical activity might decrease the risk of prostate cancer. We ascertained lifetime measures of activity in a population-based case-control study of prostate cancer in Shanghai, China to investigate physical activity in a population where the incidence of prostate cancer is low but rising. In all, 238 men with prostate cancer, diagnosed 1993-1995, were identified through a rapid reporting system. A second group of 206 men with benign prostatic hyperplasia (BPH) was matched to prostate cancer cases, and 471 age-matched and population-based controls were identified from urban Shanghai. Through personal interviews, we ascertained all daily, occupational, and recreational activities at ages 20-29, ages 40-49, and in 1988 to generate hours spent sleeping, sitting, in moderate activity, and in vigorous activity. Time spent per week in different activities was converted to metabolic equivalents (MET-h) and energy expended. Time spent in, MET-h of, and energy expended in physical activities were not consistently related to either prostate cancer or BPH when compared to controls. Few men reported regular vigorous activity. Occupational activity, based on an energy expenditure index using job titles, was suggestively associated with a decreased risk of BPH, but not associated with prostate cancer. Associations did not vary according to age or stage of prostate cancer at diagnosis. Our results, based on regular physical activity, occupational activity, hours in activities, MET-h, and energy expended, did not support a protective role of physical activity in prostate cancer or BPH for men in a low-risk population.

  14. Population Stratification in the Context of Diverse Epidemiologic Surveys Sans Genome-Wide Data

    PubMed Central

    Oetjens, Matthew T.; Brown-Gentry, Kristin; Goodloe, Robert; Dilks, Holli H.; Crawford, Dana C.

    2016-01-01

    Population stratification or confounding by genetic ancestry is a potential cause of false associations in genetic association studies. Estimation of and adjustment for genetic ancestry has become common practice thanks in part to the availability of ancestry informative markers on genome-wide association study (GWAS) arrays. While array data is now widespread, these data are not ubiquitous as several large epidemiologic and clinic-based studies lack genome-wide data. One such large epidemiologic-based study lacking genome-wide data accessible to investigators is the National Health and Nutrition Examination Surveys (NHANES), population-based cross-sectional surveys of Americans linked to demographic, health, and lifestyle data conducted by the Centers for Disease Control and Prevention. DNA samples (n = 14,998) were extracted from biospecimens from consented NHANES participants between 1991–1994 (NHANES III, phase 2) and 1999–2002 and represent three major self-identified racial/ethnic groups: non-Hispanic whites (n = 6,634), non-Hispanic blacks (n = 3,458), and Mexican Americans (n = 3,950). We as the Epidemiologic Architecture for Genes Linked to Environment study genotyped candidate gene and GWAS-identified index variants in NHANES as part of the larger Population Architecture using Genomics and Epidemiology I study for collaborative genetic association studies. To enable basic quality control such as estimation of genetic ancestry to control for population stratification in NHANES san genome-wide data, we outline here strategies that use limited genetic data to identify the markers optimal for characterizing genetic ancestry. From among 411 and 295 autosomal SNPs available in NHANES III and NHANES 1999–2002, we demonstrate that markers with ancestry information can be identified to estimate global ancestry. Despite limited resolution, global genetic ancestry is highly correlated with self-identified race for the majority of participants, although less so for ethnicity. Overall, the strategies outlined here for a large epidemiologic study can be applied to other datasets accessible for genotype–phenotype studies but are sans genome-wide data. PMID:27200085

  15. Healthcare cost savings estimator tool for chronic disease self-management program: a new tool for program administrators and decision makers.

    PubMed

    Ahn, SangNam; Smith, Matthew Lee; Altpeter, Mary; Post, Lindsey; Ory, Marcia G

    2015-01-01

    Chronic disease self-management education (CDSME) programs have been delivered to more than 100,000 older Americans with chronic conditions. As one of the Stanford suite of evidence-based CDSME programs, the chronic disease self-management program (CDSMP) has been disseminated in diverse populations and settings. The objective of this paper is to introduce a practical, universally applicable tool to assist program administrators and decision makers plan implementation efforts and make the case for continued program delivery. This tool was developed utilizing data from a recent National Study of CDSMP to estimate national savings associated with program participation. Potential annual healthcare savings per CDSMP participant were calculated based on averted emergency room visits and hospitalizations. While national data can be utilized to estimate cost savings, the tool has built-in features allowing users to tailor calculations based on their site-specific data. Building upon the National Study of CDSMP's documented potential savings of $3.3 billion in healthcare costs by reaching 5% of adults with one or more chronic conditions, two heuristic case examples were also explored based on different population projections. The case examples show how a small county and large metropolitan city were not only able to estimate healthcare savings ($38,803 for the small county; $732,290 for the large metropolitan city) for their existing participant populations but also to project significant healthcare savings if they plan to reach higher proportions of middle-aged and older adults. Having a tool to demonstrate the monetary value of CDSMP can contribute to the ongoing dissemination and sustainability of such community-based interventions. Next steps will be creating a user-friendly, internet-based version of Healthcare Cost Savings Estimator Tool: CDSMP, followed by broadening the tool to consider cost savings for other evidence-based programs.

  16. A Place-Oriented, Mixed-Level Regionalization Method for Constructing Geographic Areas in Health Data Dissemination and Analysis

    PubMed Central

    Mu, Lan; Wang, Fahui; Chen, Vivien W.; Wu, Xiao-Cheng

    2015-01-01

    Similar geographic areas often have great variations in population size. In health data management and analysis, it is desirable to obtain regions of comparable population by decomposing areas of large population (to gain more spatial variability) and merging areas of small population (to mask privacy of data). Based on the Peano curve algorithm and modified scale-space clustering, this research proposes a mixed-level regionalization (MLR) method to construct geographic areas with comparable population. The method accounts for spatial connectivity and compactness, attributive homogeneity, and exogenous criteria such as minimum (and approximately equal) population or disease counts. A case study using Louisiana cancer data illustrates the MLR method and its strengths and limitations. A major benefit of the method is that most upper level geographic boundaries can be preserved to increase familiarity of constructed areas. Therefore, the MLR method is more human-oriented and place-based than computer-oriented and space-based. PMID:26251551

  17. Association of infectious mononucleosis with multiple sclerosis. A population-based study.

    PubMed

    Ramagopalan, Sreeram V; Valdar, William; Dyment, David A; DeLuca, Gabriele C; Yee, Irene M; Giovannoni, Gavin; Ebers, George C; Sadovnick, A Dessa

    2009-01-01

    Genetic and environmental factors have important roles in multiple sclerosis (MS) susceptibility. Several studies have attempted to correlate exposure to viral illness with the subsequent development of MS. Here in a population-based Canadian cohort, we investigate the relationship between prior clinical infection or vaccination and the risk of MS. Using the longitudinal Canadian database, 14,362 MS index cases and 7,671 spouse controls were asked about history of measles, mumps, rubella, varicella and infectious mononucleosis as well as details about vaccination with measles, mumps, rubella, hepatitis B and influenza vaccines. Comparisons were made between cases and spouse controls. Spouse controls and stratification by sex appear to correct for ascertainment bias because with a single exception we found no significant differences between cases and controls for all viral exposures and vaccinations. However, 699 cases and 165 controls reported a history of infectious mononucleosis (p < 0.001, corrected odds ratio 2.06, 95% confidence interval 1.71-2.48). Females were more aware of disease history than males (p < 0.001). The data further confirms a reporting distortion between males and females. Historically reported measles, mumps, rubella, varicella and vaccination for hepatitis B, influenza, measles, mumps and rubella are not associated with increased risk of MS later in life. A clinical history of infectious mononucleosis is conspicuously associated with increased MS susceptibility. These findings support studies implicating Epstein-Barr virus in MS disease susceptibility, but a co-association between MS susceptibility and clinically apparent infectious mononucleosis cannot be excluded.

  18. Driving following Kava Use and Road Traffic Injuries: A Population-Based Case-Control Study in Fiji (TRIP 14)

    PubMed Central

    Wainiqolo, Iris; Kafoa, Berlin; Kool, Bridget; Robinson, Elizabeth; Herman, Josephine; McCaig, Eddie; Ameratunga, Shanthi

    2016-01-01

    Objective To investigate the association between kava use and the risk of four-wheeled motor vehicle crashes in Fiji. Kava is a traditional beverage commonly consumed in many Pacific Island Countries. Herbal anxiolytics containing smaller doses of kava are more widely available. Methods Data for this population-based case-control study were collected from drivers of ‘case’ vehicles involved in serious injury-involved crashes (where at least one road user was killed or admitted to hospital for 12 hours or more) and ‘control’ vehicles representative of ‘driving time’ in the study base. Structured interviewer administered questionnaires collected self-reported participant data on demographic characteristics and a range of risk factors including kava use and potential confounders. Unconditional logistic regression models estimated odds ratios relating to the association between kava use and injury-involved crash risk. Findings Overall, 23% and 4% of drivers of case and control vehicles, respectively, reported consuming kava in the 12 hours prior to the crash or road survey. After controlling for assessed confounders, driving following kava use was associated with a four-fold increase in the odds of crash involvement (Odds ratio: 4.70; 95% CI: 1.90–11.63). The related population attributable risk was 18.37% (95% CI: 13.77–22.72). Acknowledging limited statistical power, we did not find a significant interaction in this association with concurrent alcohol use. Conclusion In this study conducted in a setting where recreational kava consumption is common, driving following the use of kava was associated with a significant excess of serious-injury involved road crashes. The precautionary principle would suggest road safety strategies should explicitly recommend avoiding driving following kava use, particularly in communities where recreational use is common. PMID:26930404

  19. A randomized controlled open trial of population-based disease and case management in a Medicare Plus Choice health maintenance organization.

    PubMed

    Martin, David C; Berger, Marc L; Anstatt, David T; Wofford, Jonathan; Warfel, DeAnn; Turpin, Robin S; Cannuscio, Carolyn C; Teutsch, Steven M; Mansheim, Bernard J

    2004-10-01

    The object of this study was to examine the effect of population-based disease management and case management on resource use, self-reported health status, and member satisfaction with and retention in a Medicare Plus Choice health maintenance organization (HMO). Study design consisted of a prospective, randomized controlled open trial of 18 months' duration. Participants were 8504 Medicare beneficiaries aged 65 and older who had been continuously enrolled for at least 12 months in a network model Medicare Plus Choice HMO serving a contiguous nine-county metropolitan area. Members were care managed with an expert clinical information system and frequent telephone contact. Main outcomes included self-reported health status measured by the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), resource use measured by admission rates and bed-days per thousand per year, member satisfaction, and costs measured by paid claims. More favorable outcomes occurred in the intervention group for satisfaction with the health plan (P < .01) and the social function domain as measured by SF-36 (P = .04). There was no difference in member retention or mortality between groups. Use of skilled nursing home services was significantly lower in the intervention group than in the control (616 vs 747 days per thousand members per year, P = .02). This reduction, however, did not lead to lower mean total expenditures in the intervention group compared with the control (6828 dollars per member for 18 months vs 7001 dollars, P = .61). Population-based disease management and case management led to improved self-reported satisfaction and social function but not to a global net decrease in resource use or improved member retention.

  20. Reduced-Order Models for Load Management in the Power Grid

    NASA Astrophysics Data System (ADS)

    Alizadeh, Mahnoosh

    In recent years, considerable research efforts have been directed towards designing control schemes that can leverage the inherent flexibility of electricity demand that is not tapped into in today's electricity markets. It is expected that these control schemes will be carried out by for-profit entities referred to as aggregators that operate at the edge of the power grid network. While the aggregator control problem is receiving much attention, more high-level questions of how these aggregators should plan their market participation, interact with the main grid and with each other, remain rather understudied. Answering these questions requires a large-scale model for the aggregate flexibility that can be harnessed from the a population of customers, particularly for residences and small businesses. The contribution of this thesis towards this goal is divided into three parts: In Chapter 3, a reduced-order model for a large population of heterogeneous appliances is provided by clustering load profiles that share similar degrees of freedom together. The use of such reduced-order model for system planning and optimal market decision making requires a foresighted approximation of the number of appliances that will join each cluster. Thus, Chapter 4 provides a systematic framework to generate such forecasts for the case of Electric Vehicles, based on real-world battery charging data. While these two chapters set aside the economic side that is naturally involved with participation in demand response programs and mainly focus on the control problem, Chapter 5 is dedicated to the study of optimal pricing mechanisms in order to recruit heterogeneous customers in a demand response program in which an aggregator can directly manage their appliances' load under their specified preferences. Prices are proportional to the wholesale market savings that can result from each recruitment event.

  1. Estimating Epilepsy Incidence and Prevalence in the US Pediatric Population Using Nationwide Health Insurance Claims Data.

    PubMed

    Kim, Hyunmi; Thurman, David J; Durgin, Tracy; Faught, Edward; Helmers, Sandra

    2016-05-01

    This study aims to determine prevalence and incidence of epilepsy in the US pediatric population. We analyzed commercial claims and Medicaid insurance claims data between 2008 and 2012. Over 8 million continuously enrolled lives aged 0 to 19 years were included. Our definition of a prevalent case of epilepsy was based on International Classification of Diseases-coded diagnoses of epilepsy or seizures and evidence of prescribed antiepileptic drugs. Incident cases were identified in subjects continuously enrolled for ≥2 years of which the first 2 years had no indication of epilepsy or seizures. The overall prevalence estimate for 2012 was 6.8 per 1,000 children. The overall incidence estimate for 2012 was 104 per 100,000 pediatric population. This study provides estimates of the prevalence and incidence of epilepsy in the US pediatric population, using large claims datasets from multiple US population sectors. The findings appear reasonably representative of the US-insured pediatric population. © The Author(s) 2015.

  2. Development and Validation of a Predictive Model to Identify Individuals Likely to Have Undiagnosed Chronic Obstructive Pulmonary Disease Using an Administrative Claims Database.

    PubMed

    Moretz, Chad; Zhou, Yunping; Dhamane, Amol D; Burslem, Kate; Saverno, Kim; Jain, Gagan; Devercelli, Giovanna; Kaila, Shuchita; Ellis, Jeffrey J; Hernandez, Gemzel; Renda, Andrew

    2015-12-01

    Despite the importance of early detection, delayed diagnosis of chronic obstructive pulmonary disease (COPD) is relatively common. Approximately 12 million people in the United States have undiagnosed COPD. Diagnosis of COPD is essential for the timely implementation of interventions, such as smoking cessation programs, drug therapies, and pulmonary rehabilitation, which are aimed at improving outcomes and slowing disease progression. To develop and validate a predictive model to identify patients likely to have undiagnosed COPD using administrative claims data. A predictive model was developed and validated utilizing a retro-spective cohort of patients with and without a COPD diagnosis (cases and controls), aged 40-89, with a minimum of 24 months of continuous health plan enrollment (Medicare Advantage Prescription Drug [MAPD] and commercial plans), and identified between January 1, 2009, and December 31, 2012, using Humana's claims database. Stratified random sampling based on plan type (commercial or MAPD) and index year was performed to ensure that cases and controls had a similar distribution of these variables. Cases and controls were compared to identify demographic, clinical, and health care resource utilization (HCRU) characteristics associated with a COPD diagnosis. Stepwise logistic regression (SLR), neural networking, and decision trees were used to develop a series of models. The models were trained, validated, and tested on randomly partitioned subsets of the sample (Training, Validation, and Test data subsets). Measures used to evaluate and compare the models included area under the curve (AUC); index of the receiver operating characteristics (ROC) curve; sensitivity, specificity, positive predictive value (PPV); and negative predictive value (NPV). The optimal model was selected based on AUC index on the Test data subset. A total of 50,880 cases and 50,880 controls were included, with MAPD patients comprising 92% of the study population. Compared with controls, cases had a statistically significantly higher comorbidity burden and HCRU (including hospitalizations, emergency room visits, and medical procedures). The optimal predictive model was generated using SLR, which included 34 variables that were statistically significantly associated with a COPD diagnosis. After adjusting for covariates, anticholinergic bronchodilators (OR = 3.336) and tobacco cessation counseling (OR = 2.871) were found to have a large influence on the model. The final predictive model had an AUC of 0.754, sensitivity of 60%, specificity of 78%, PPV of 73%, and an NPV of 66%. This claims-based predictive model provides an acceptable level of accuracy in identifying patients likely to have undiagnosed COPD in a large national health plan. Identification of patients with undiagnosed COPD may enable timely management and lead to improved health outcomes and reduced COPD-related health care expenditures.

  3. The international limits and population at risk of Plasmodium vivax transmission in 2009.

    PubMed

    Guerra, Carlos A; Howes, Rosalind E; Patil, Anand P; Gething, Peter W; Van Boeckel, Thomas P; Temperley, William H; Kabaria, Caroline W; Tatem, Andrew J; Manh, Bui H; Elyazar, Iqbal R F; Baird, J Kevin; Snow, Robert W; Hay, Simon I

    2010-08-03

    A research priority for Plasmodium vivax malaria is to improve our understanding of the spatial distribution of risk and its relationship with the burden of P. vivax disease in human populations. The aim of the research outlined in this article is to provide a contemporary evidence-based map of the global spatial extent of P. vivax malaria, together with estimates of the human population at risk (PAR) of any level of transmission in 2009. The most recent P. vivax case-reporting data that could be obtained for all malaria endemic countries were used to classify risk into three classes: malaria free, unstable (<0.1 case per 1,000 people per annum (p.a.)) and stable (> or =0.1 case per 1,000 p.a.) P. vivax malaria transmission. Risk areas were further constrained using temperature and aridity data based upon their relationship with parasite and vector bionomics. Medical intelligence was used to refine the spatial extent of risk in specific areas where transmission was reported to be absent (e.g., large urban areas and malaria-free islands). The PAR under each level of transmission was then derived by combining the categorical risk map with a high resolution population surface adjusted to 2009. The exclusion of large Duffy negative populations in Africa from the PAR totals was achieved using independent modelling of the gene frequency of this genetic trait. It was estimated that 2.85 billion people were exposed to some risk of P. vivax transmission in 2009, with 57.1% of them living in areas of unstable transmission. The vast majority (2.59 billion, 91.0%) were located in Central and South East (CSE) Asia, whilst the remainder were located in America (0.16 billion, 5.5%) and in the Africa+ region (0.10 billion, 3.5%). Despite evidence of ubiquitous risk of P. vivax infection in Africa, the very high prevalence of Duffy negativity throughout Central and West Africa reduced the PAR estimates substantially. After more than a century of development and control, P. vivax remains more widely distributed than P. falciparum and is a potential cause of morbidity and mortality amongst the 2.85 billion people living at risk of infection, the majority of whom are in the tropical belt of CSE Asia. The probability of infection is reduced massively across Africa by the frequency of the Duffy negative trait, but transmission does occur on the continent and is a concern for Duffy positive locals and travellers. The final map provides the spatial limits on which the endemicity of P. vivax transmission can be mapped to support future cartographic-based burden estimations.

  4. Occupational exposures to engine exhausts and other PAHs and breast cancer risk: A population-based case-control study.

    PubMed

    Rai, Rajni; Glass, Deborah C; Heyworth, Jane S; Saunders, Christobel; Fritschi, Lin

    2016-06-01

    Some previous studies have suggested that exposure to engine exhausts may increase risk of breast cancer. In a population-based case-control study of breast cancer in Western Australia we assessed occupational exposure to engine exhausts using questionnaires and telephone interviews. Odds Ratios (OR) and 95% Confidence Intervals (CI) were calculated using logistic regression. We found no association between risk of breast cancer and occupational exposure to diesel exhaust (OR 1.07, 95%CI: 0.81-1.41), gasoline exhaust (OR 0.98, 95%CI: 0.74-1.28), or other exhausts (OR 1.08, 95%CI: 0.29-4.08). There were also no significant dose- or duration-response relationships. This study did not find evidence supporting the association between occupational exposures to engine exhausts and breast cancer risk. Am. J. Ind. Med. 59:437-444, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Artificial sweeteners and absence of bladder cancer risk in Copenhagen.

    PubMed

    Møller-Jensen, O; Knudsen, J B; Sørensen, B L; Clemmesen, J

    1983-11-15

    During the years 1979 to 1981 a population-based case-control study of bladder cancer including papillomas was performed in Greater Copenhagen. After exclusions some 388 patients (290 males; 98 females) and an age- and sex-matched group of 787 controls (592 males; 195 females) remained for analysis. Controls were selected at random from the general population of the study area. All persons were interviewed concerning use of artificial sweeteners in addition to their exposure to a number of other known or suspected risk factors for bladder cancer. Fifty-five male bladder cancer patients (19.4%) and 150 controls (25.7%) had at some time used artificial sweeteners regularly. Among females 27.1% of cases and 25.9% of controls regularly used sweeteners. In neither sex was the relative risk significantly increased in users compared with non-users of artificial sweeteners. The relative risk of 0.78 in the two sexes combined was not significantly different from 1.0 (95% C.I.: 0.58-1.05). There was no indication of a regular increase in risk with increasing daily consumption of table-top sweeteners nor was there any indication of an increase in risk with a duration of regular use of artificial sweeteners. Taking into account a possible latency period between first regular use and bladder cancer development did not change the finding of an absence of association between use of artificial sweeteners and the risk of bladder cancer. Neither saccharine nor cyclamate users had an increased risk of bladder cancer. This population-based case-control investigation provides further evidence that it is highly unlikely that the consumption of artificial sweeteners has contributed to current bladder cancer rates in man.

  6. A population-based case-control study of urinary arsenic species and squamous cell carcinoma in New Hampshire, USA.

    PubMed

    Gilbert-Diamond, Diane; Li, Zhigang; Perry, Ann E; Spencer, Steven K; Gandolfi, A Jay; Karagas, Margaret R

    2013-10-01

    Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States. We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population. We conducted a population-based case-control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and summed these arsenic species (ΣAs). Because seafood contains arsenolipids and arsenosugars that metabolize into DMA through alternate pathways, participants who reported seafood consumption within 2 days before urine collection were excluded from the analyses. In adjusted logistic regression analyses (323 cases, 319 controls), the SCC odds ratio (OR) was 1.37 for each ln-transformed microgram per liter increase in ln-transformed ΣAs concentration [ln(ΣAs)] (95% CI: 1.04, 1.80). Urinary ln(MMA) and ln(DMA) also were positively associated with SCC (OR = 1.34; 95% CI: 1.04, 1.71 and OR = 1.34; 95% CI: 1.03, 1.74, respectively). A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49). Percent iAs, MMA, and DMA were not associated with SCC. These results suggest that arsenic exposure at levels common in the United States relates to SCC and that arsenic metabolism ability does not modify the association.

  7. FTO Is Associated with Aortic Valve Stenosis in a Gender Specific Manner of Heterozygote Advantage: A Population-Based Case-Control Study.

    PubMed

    Thron, Cindy; Akhyari, Payam; Godehardt, Erhard; Lichtenberg, Artur; Rüther, Ulrich; Seehaus, Stefanie

    2015-01-01

    Single nucleotide polymorphisms (SNPs) within the Fat mass and obesity associated (FTO) gene have been linked with increased body weight. However, the data on an association of FTO with cardiovascular diseases remains conflicting. Therefore, we ascertained whether FTO is associated with aortic valve stenosis (AVS), one of the most frequent cardiovascular diseases in the Western world. In this population-based case-control study the FTO SNP rs9939609 was analyzed in 300 German patients with AVS and 429 German controls of the KORA survey S4, representing a random population. Blood samples were collected prior to aortic valve replacement in AVS cases and FTO rs9939609 was genotyped via ARMS-PCR. Genotype frequencies differed significantly between AVS cases and KORA controls (p = 0.004). Separate gender-analyses uncovered an association of FTO with AVS exclusively in males; homozygote carriers for the risk-allele (A) had a higher risk to develop AVS (p = 0.017, odds ratio (OR) 1.727; 95% confidence interval (CI) 1.087-2.747, recessive model), whereas heterozygote carriers for the risk-allele showed a lower risk (p = 0.002, OR 0.565, 95% CI 0.384-0.828, overdominant model). After adjustment for multiple co-variables, the odds ratios of heterozygotes remained significant for an association with AVS (p = 0.008, OR 0.565, 95% CI 0.369-0.861). This study revealed an association of FTO rs9939609 with AVS. Furthermore, this association was restricted to men, with heterozygotes having a significantly lower chance to develop AVS. Lastly, the association between FTO and AVS was independent of BMI and other variables such as diabetes mellitus.

  8. Exposure to Genocide as a Risk Factor for Homicide Perpetration in Rwanda: A Population-Based Case-Control Study.

    PubMed

    Rubanzana, Wilson; Hedt-Gauthier, Bethany L; Ntaganira, Joseph; Freeman, Michael D

    2018-06-01

    A population-based case-control study was conducted to assess the relationship between genocide exposure and homicide perpetration in Rwanda. A sample of 150 homicide perpetrators who were charged with and confessed to having committed homicide between 1 May 2011 and 31 May 2013 and 450 controls were enrolled. Cases were matched to controls by neighborhood, age and sex. Socio-demographic, background and genocide-related information was collected from study subjects' next of kin. Four characteristics of genocide exposure were: genocide survivor, genocide perpetrator, having lost a first-degree relative to genocide and having a first-degree relative convicted of genocide. We assessed the impact of each genocide-exposure variable using conditional logistic regression. Of the 150 cases, 124 (82.7%) were male and 26 (17.3%) were female. The mean age of the alleged homicide perpetrators was 33 years, with a peak in the age group 20-29 years (39.3%). After adjusting for socio-demographic characteristics and past common criminal records, having a first-degree relative who had been convicted of genocide crimes was a significant predictor for homicide perpetration (odds ratio [OR] = 14.4, 95% confidence interval [CI] = 1.6-129.4). Being a genocide perpetrator, a genocide survivor and having lost a first-degree family member to genocide were not identified as risk factors for homicide perpetration. In Rwanda, young people who experienced early exposure to trauma by witnessing their first-degree relatives' active participation in the genocide, are more likely to commit homicide. Socio-economic and psychotherapeutic programs targeting this population group are needed to rehabilitate these young people for violent behavior change.

  9. FTO Is Associated with Aortic Valve Stenosis in a Gender Specific Manner of Heterozygote Advantage: A Population-Based Case-Control Study

    PubMed Central

    Thron, Cindy; Akhyari, Payam; Godehardt, Erhard; Lichtenberg, Artur; Rüther, Ulrich; Seehaus, Stefanie

    2015-01-01

    Background Single nucleotide polymorphisms (SNPs) within the Fat mass and obesity associated (FTO) gene have been linked with increased body weight. However, the data on an association of FTO with cardiovascular diseases remains conflicting. Therefore, we ascertained whether FTO is associated with aortic valve stenosis (AVS), one of the most frequent cardiovascular diseases in the Western world. Methods and Findings In this population-based case-control study the FTO SNP rs9939609 was analyzed in 300 German patients with AVS and 429 German controls of the KORA survey S4, representing a random population. Blood samples were collected prior to aortic valve replacement in AVS cases and FTO rs9939609 was genotyped via ARMS-PCR. Genotype frequencies differed significantly between AVS cases and KORA controls (p = 0.004). Separate gender-analyses uncovered an association of FTO with AVS exclusively in males; homozygote carriers for the risk-allele (A) had a higher risk to develop AVS (p = 0.017, odds ratio (OR) 1.727; 95% confidence interval (CI) 1.087–2.747, recessive model), whereas heterozygote carriers for the risk-allele showed a lower risk (p = 0.002, OR 0.565, 95% CI 0.384–0.828, overdominant model). After adjustment for multiple co-variables, the odds ratios of heterozygotes remained significant for an association with AVS (p = 0.008, OR 0.565, 95% CI 0.369–0.861). Conclusions This study revealed an association of FTO rs9939609 with AVS. Furthermore, this association was restricted to men, with heterozygotes having a significantly lower chance to develop AVS. Lastly, the association between FTO and AVS was independent of BMI and other variables such as diabetes mellitus. PMID:26431034

  10. Infections and the risk of incident giant cell arteritis: a population-based, case-control study.

    PubMed

    Rhee, Rennie L; Grayson, Peter C; Merkel, Peter A; Tomasson, Gunnar

    2017-06-01

    Alterations in the immune system and infections are suspected to increase susceptibility to giant cell arteritis (GCA). Recently herpes zoster has been directly implicated in the pathogenesis of GCA. We examined the association between prior infections, in particular herpes zoster, and incident GCA in a population-based cohort. A nested case-control study was performed using an electronic database from the UK. Cases with newly diagnosed GCA were identified using a validated algorithm and compared with age-matched, sex-matched and practice-matched controls. Conditional logistic regression was used to examine the relationship between any infection or herpes zoster infection on the development of GCA after adjusting for potential confounders; results were expressed as incidence rate ratios (IRRs). There were 4559 cases of GCA and 22 795 controls. Any prior infection and herpes zoster were associated with incident GCA (IRR 1.26 (95% CI 1.16 to 1.36), p<0.01; and 1.17 (95% CI 1.04 to 1.32), p<0.01, respectively). A greater number of infections was associated with a higher risk of developing GCA (IRR for 1, 2-4 and ≥5 infections was 1.28, 1.60 and 2.18, respectively). Antecedent infections and, to a lesser extent, herpes zoster infections are modestly associated with incident GCA. These data provide population-level support for the hypothesis that long-standing alterations of the immune system are associated with susceptibility to GCA and suggest that herpes zoster is unlikely to play a major causal role in the pathogenesis of GCA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. The Case for Diabetes Population Health Improvement: Evidence-Based Programming for Population Outcomes in Diabetes.

    PubMed

    Golden, Sherita Hill; Maruthur, Nisa; Mathioudakis, Nestoras; Spanakis, Elias; Rubin, Daniel; Zilbermint, Mihail; Hill-Briggs, Felicia

    2017-07-01

    The goal of this review is to describe diabetes within a population health improvement framework and to review the evidence for a diabetes population health continuum of intervention approaches, including diabetes prevention and chronic and acute diabetes management, to improve clinical and economic outcomes. Recent studies have shown that compared to usual care, lifestyle interventions in prediabetes lower diabetes risk at the population-level and that group-based programs have low incremental medial cost effectiveness ratio for health systems. Effective outpatient interventions that improve diabetes control and process outcomes are multi-level, targeting the patient, provider, and healthcare system simultaneously and integrate community health workers as a liaison between the patient and community-based healthcare resources. A multi-faceted approach to diabetes management is also effective in the inpatient setting. Interventions shown to promote safe and effective glycemic control and use of evidence-based glucose management practices include provider reminder and clinical decision support systems, automated computer order entry, provider education, and organizational change. Future studies should examine the cost-effectiveness of multi-faceted outpatient and inpatient diabetes management programs to determine the best financial models for incorporating them into diabetes population health strategies.

  12. Young People's Risk of Suicide Attempts in Relation to Parental Death: A Population-Based Register Study

    ERIC Educational Resources Information Center

    Jakobsen, Ida Skytte; Christiansen, Erik

    2011-01-01

    Background: The objective of this study was to examine the association between the death of a biological parent and subsequent suicide attempts by young people (aged 10-22 years), and to explore sociodemographic factors as modifying factors in the process. Methods: The study used a nested case-control design. The full study population was obtained…

  13. Safety Case Development as an Information Modelling Problem

    NASA Astrophysics Data System (ADS)

    Lewis, Robert

    This paper considers the benefits from applying information modelling as the basis for creating an electronically-based safety case. It highlights the current difficulties of developing and managing large document-based safety cases for complex systems such as those found in Air Traffic Control systems. After a review of current tools and related literature on this subject, the paper proceeds to examine the many relationships between entities that can exist within a large safety case. The paper considers the benefits to both safety case writers and readers from the future development of an ideal safety case tool that is able to exploit these information models. The paper also introduces the idea that the safety case has formal relationships between entities that directly support the safety case argument using a methodology such as GSN, and informal relationships that provide links to direct and backing evidence and to supporting information.

  14. Forecasting Malaria in the Western Amazon

    NASA Astrophysics Data System (ADS)

    Pan, W. K.; Zaitchik, B. F.; Pizzitutti, F.; Berky, A.; Feingold, B.; Mena, C.; Janko, M.

    2017-12-01

    Reported cases of malaria in the western Amazon regions of Peru, Colombia and Ecuador have more than tripled since 2011. Responding to this epidemic has been challenging given large-scale environmental impacts and demographic changes combined with changing financial and political priorities. In Peru alone, malaria cases increased 5-fold since 2011. Reasons include changes in the Global Malaria Fund, massive flooding in 2012, the "mega" El Nino in 2016, and continued natural resource extraction via logging and mining. These challenges prompted the recent creation of the Malaria Cero program in 2017 with the goal to eradicate malaria by 2021. To assist in malaria eradiation, a team of investigators supported by NASA have been developing an Early Warning System for Malaria. The system leverages demographic, epidemiological, meteorological and land use/cover data to develop a four-component system that will improve detection of malaria across the western Amazon Basin. System components include a land data assimilation system (LDAS) to estimate past and future hydrological states and flux, a seasonal human population model to estimate population at risk and spatial connectivity to high risk transmission areas, a sub-regional statistical model to identify when and where observed malaria cases have exceeded those expected, and an Agent Based Model (ABM) to integrate human, environmental, and entomological transmission dynamics with potential strategies for control. Data include: daily case detection reports between 2000 and 2017 from all health posts in the region of Loreto in the northern Peruvian Amazon; LDAS outputs (precipitation, temperature, humidity, solar radiation) at a 1km and weekly scale; satellite-derived estimates of land cover; and human population size from census and health data. This presentation will provide an overview of components, focusing on how the system identifies an outbreak and plans for technology transfer.

  15. Dopamine transporter (DAT1) VNTR polymorphism and alcoholism in two culturally different populations of south India.

    PubMed

    Bhaskar, Lakkakula V K S; Thangaraj, Kumarasamy; Wasnik, Samiksha; Singh, Lalji; Raghavendra Rao, Vadlamudi

    2012-01-01

    It is well established that the central dopaminergic reward pathway is likely involved in alcohol intake and the progression of alcohol dependence. Dopamine transporter (DAT1) mediates the active re-uptake of DA from the synapse and is a principal regulator of dopaminergic neurotransmission. The gene for the human DAT1 displays several polymorphisms, including a 40-bp variable number of tandem repeats (VNTR) ranging from 3 to 16 copies in the 3'-untranslated region (UTR) of the gene. To assess the role of this gene in alcoholism, we genotyped the VNTR of DAT1 gene in a sample of 206 subjects from the Kota population (111 alcohol dependence cases and 95 controls) and 142 subjects from Badaga population (81 alcohol dependence cases and 61 controls). Both populations inhabit a similar environmental zone, but have different ethnic histories. Phenotype was defined based on the DSM-IV criteria. Genotyping was performed using PCR and electrophoresis. The association of DAT1 with alcoholism was tested by using the Clump v1.9 program which uses the Monte Carlo method. In both Kota and Badaga populations, the allele A10 was the most frequent allele followed by allele A9. The genotypic distribution is in Hardy-Weinberg equilibrium in both cases and control groups of Kota and Badaga populations. The DAT1 VNTR was significantly associated with alcoholism in Badaga population but not in Kota population. Our results suggest that the A9 allele of the DAT gene is involved in vulnerability to alcoholism, but that these associations are population specific. Copyright © American Academy of Addiction Psychiatry.

  16. Evidence for the effect of disease management: is $1 billion a year a good investment?

    PubMed

    Mattke, Soeren; Seid, Michael; Ma, Sai

    2007-12-01

    To assess the evidence for the effect of disease management on quality of care, disease control, and cost, with a focus on population-based programs. Literature review. We conducted a literature search for and a structured review of studies on population-based disease management programs, as well as for reviews and meta-analyses of disease management interventions. We identified 3 evaluations of large-scale population-based programs, as well as 10 meta-analyses and 16 systematic reviews, covering 317 unique studies. We found consistent evidence that disease management improves processes of care and disease control but no conclusive support for its effect on health outcomes. Overall, disease management does not seem to affect utilization except for a reduction in hospitalization rates among patients with congestive heart failure and an increase in outpatient care and prescription drug use among patients with depression. When the costs of the intervention were appropriately accounted for and subtracted from any savings, there was no conclusive evidence that disease management leads to a net reduction of direct medical costs. Although disease management seems to improve quality of care, its effect on cost is uncertain. Most of the evidence to date addresses small-scale programs targeting high-risk individuals, while only 3 studies evaluate large population-based interventions, implying that little is known about their effect. Payers and policy makers should remain skeptical about vendor claims and should demand supporting evidence based on transparent and scientifically sound methods.

  17. Medicare utilization, screening, and costs among participants in the Southeastern Diabetes Initiative: A population-based evaluation.

    PubMed

    Van Houtven, Courtney H; Greiner, Melissa A; Heidenfelder, Brooke; Spratt, Susan E; Granger, Bradi B; Dunham, Ashley A; Qualls, Laura G; Curtis, Lesley H

    2018-04-01

    Type 2 diabetes mellitus imposes significant burdens on patients and health care systems. Population-level interventions are being implemented to reach large numbers of patients at risk of or diagnosed with diabetes. We describe a population-based evaluation of the Southeastern Diabetes Initiative (SEDI) from the perspective of a payer, the Centers for Medicare & Medicaid Services (CMS). The purpose of this paper is to describe the population-based evaluation approach of the SEDI intervention from a Medicare utilization and cost perspective. We measured associations between the SEDI intervention and receipt of diabetes screening (i.e., HbA1c test, eye exam, lipid profile), health care resource use, and costs among intervention enrollees, compared with a control cohort of Medicare beneficiaries in geographically adjacent counties. The intervention cohort had slightly lower 1-year screening in 2 of 3 domains (4% for HbA1c; 9% for lipid profiles) in the post-intervention period, compared with the control cohort. The SEDI intervention cohort did not have different Medicare utilization or total Medicare costs in the post-intervention period from surrounding control counties. Our analytic approach may be useful to others evaluating CMS demonstration projects in which population-level health is targeted for improvement in a well-defined clinical population. Published by Elsevier Ltd.

  18. Multimethod, multistate Bayesian hierarchical modeling approach for use in regional monitoring of wolves.

    PubMed

    Jiménez, José; García, Emilio J; Llaneza, Luis; Palacios, Vicente; González, Luis Mariano; García-Domínguez, Francisco; Múñoz-Igualada, Jaime; López-Bao, José Vicente

    2016-08-01

    In many cases, the first step in large-carnivore management is to obtain objective, reliable, and cost-effective estimates of population parameters through procedures that are reproducible over time. However, monitoring predators over large areas is difficult, and the data have a high level of uncertainty. We devised a practical multimethod and multistate modeling approach based on Bayesian hierarchical-site-occupancy models that combined multiple survey methods to estimate different population states for use in monitoring large predators at a regional scale. We used wolves (Canis lupus) as our model species and generated reliable estimates of the number of sites with wolf reproduction (presence of pups). We used 2 wolf data sets from Spain (Western Galicia in 2013 and Asturias in 2004) to test the approach. Based on howling surveys, the naïve estimation (i.e., estimate based only on observations) of the number of sites with reproduction was 9 and 25 sites in Western Galicia and Asturias, respectively. Our model showed 33.4 (SD 9.6) and 34.4 (3.9) sites with wolf reproduction, respectively. The number of occupied sites with wolf reproduction was 0.67 (SD 0.19) and 0.76 (0.11), respectively. This approach can be used to design more cost-effective monitoring programs (i.e., to define the sampling effort needed per site). Our approach should inspire well-coordinated surveys across multiple administrative borders and populations and lead to improved decision making for management of large carnivores on a landscape level. The use of this Bayesian framework provides a simple way to visualize the degree of uncertainty around population-parameter estimates and thus provides managers and stakeholders an intuitive approach to interpreting monitoring results. Our approach can be widely applied to large spatial scales in wildlife monitoring where detection probabilities differ between population states and where several methods are being used to estimate different population parameters. © 2016 Society for Conservation Biology.

  19. Population-expression models of immune response

    NASA Astrophysics Data System (ADS)

    Stromberg, Sean P.; Antia, Rustom; Nemenman, Ilya

    2013-06-01

    The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable.

  20. Candidate genes for alcohol dependence: A genetic association study from India.

    PubMed

    Malhotra, Savita; Basu, Debasish; Khullar, Madhu; Ghosh, Abhishek; Chugh, Neera

    2016-11-01

    Search for candidate genes for alcohol dependence (AD) has been inconsistent and inconclusive. Moreover, most of the research has been confined to a few specific ethnic groups. Hence, the aim of our study was to explore specific candidate genes for AD in north Indian male population. In this clinic-based genetic association study, 210 males with AD and 200 controls matched for age, gender and ethnicity were recruited from the clinic and the general population, respectively. Cases were diagnosed with Semi-structured Assessment for Genetics of Alcoholism-II (SSAGA-II). Single-nucleotide polymorphism genotyping was done by real-time quantitative-polymerase chain reaction (PCR) using Taq Man assay (ABI 7500) fast real-time PCR system. Both at the genotypic level and at allelic frequency, Met158 variant of catechol-O-methyl transferase (COMT) showed significant increase in cases as compared to controls. The frequency of heterozygous genotype (A/G) of gamma-aminobutyric acid receptor A1 (GABRA1) was significantly lower in cases as compared to controls. Likewise, for GABRA2, the frequency of homozygous recessive genotype (G/G) was significantly higher in the control group. With respect to the 5-hydroxytryptamine (5HT) transporter long promoter region (5HTTLPR), cholinergic receptor muscarinic (CHRM2) and alcohol dehydrogenase 1B (ADH1B) genes, there was no significant difference between the cases and the controls. Aldehyde dehydrogenase (ALDH2) gene was found to be monomorphic in our study population. Our study findings showed COMT polymorphism conferring risk and GABRA polymorphism as a protective genotype for Indian male with AD. Genes for alcohol metabolism, serotonin transporter and cholinergic receptor gene polymorphism were perhaps not contributory to AD for Indian population.

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