Pretreatment Serum Concentrations of 25-Hydroxyvitamin D and Breast Cancer Prognostic Characteristics: A Case-Control and a Case-Series Study

PubMed Central

Yao, Song; Sucheston, Lara E.; Millen, Amy E.; Johnson, Candace S.; Trump, Donald L.; Nesline, Mary K.; Davis, Warren; Hong, Chi-Chen; McCann, Susan E.; Hwang, Helena; Kulkarni, Swati; Edge, Stephen B.; O'Connor, Tracey L.; Ambrosone, Christine B.

2011-01-01

Background Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity. Methods and Findings In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08–0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22–0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses. Conclusion In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for reducing breast cancer risk, particularly those with poor prognostic characteristics among premenopausal women. PMID:21386992

An approach to checking case-crossover analyses based on equivalence with time-series methods.

PubMed

Lu, Yun; Symons, James Morel; Geyh, Alison S; Zeger, Scott L

2008-03-01

The case-crossover design has been increasingly applied to epidemiologic investigations of acute adverse health effects associated with ambient air pollution. The correspondence of the design to that of matched case-control studies makes it inferentially appealing for epidemiologic studies. Case-crossover analyses generally use conditional logistic regression modeling. This technique is equivalent to time-series log-linear regression models when there is a common exposure across individuals, as in air pollution studies. Previous methods for obtaining unbiased estimates for case-crossover analyses have assumed that time-varying risk factors are constant within reference windows. In this paper, we rely on the connection between case-crossover and time-series methods to illustrate model-checking procedures from log-linear model diagnostics for time-stratified case-crossover analyses. Additionally, we compare the relative performance of the time-stratified case-crossover approach to time-series methods under 3 simulated scenarios representing different temporal patterns of daily mortality associated with air pollution in Chicago, Illinois, during 1995 and 1996. Whenever a model-be it time-series or case-crossover-fails to account appropriately for fluctuations in time that confound the exposure, the effect estimate will be biased. It is therefore important to perform model-checking in time-stratified case-crossover analyses rather than assume the estimator is unbiased.

Clinical Findings and Pain Symptoms as Potential Risk Factors for Chronic TMD: Descriptive Data and Empirically Identified Domains from the OPPERA Case-Control Study

PubMed Central

Ohrbach, Richard; Fillingim, Roger B.; Mulkey, Flora; Gonzalez, Yoly; Gordon, Sharon; Gremillion, Henry; Lim, Pei-Feng; Ribeiro-Dasilva, Margarete; Greenspan, Joel D.; Knott, Charles; Maixner, William; Slade, Gary

2011-01-01

Clinical characteristics might be associated with temporomandibular disorders (TMD) because they are antecedent risk factors that increase the likelihood of a healthy person developing the condition or because they represent signs or symptoms of either subclinical or overt TMD. In this baseline case-control study of the multisite Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) project, 1,633 controls and 185 cases with chronic, painful TMD completed questionnaires and received clinical examinations. Odds ratios measuring association between each clinical factor and TMD were computed, with adjustment for study-site as well as age, sex, and race/ethnicity. Compared to controls, TMD cases reported more trauma, greater parafunction, more headaches and other pain disorders, more functional limitation in using the jaw, more nonpain symptoms in the facial area, more temporomandibular joint noises and jaw locking, more neural or sensory medical conditions, and worse overall medical status. They also exhibited on examination reduced jaw mobility, more joint noises, and a greater number of painful masticatory, cervical, and body muscles upon palpation. The results indicated that TMD cases differ substantially from controls across almost all variables assessed. Future analyses of follow-up data will determine whether these clinical characteristics predict increased risk for developing first-onset pain-related TMD Perspective Clinical findings from OPPERA’s baseline case-control study indicate significant differences between chronic TMD cases and controls with respect to trauma history, parafunction, other pain disorders, health status, and clinical examination data. Future analyses will examine their contribution to TMD onset. PMID:22074750

Case-Control Genome-Wide Association Study of Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Neale, Benjamin M.; Medland, Sarah; Ripke, Stephan; Anney, Richard J. L.; Asherson, Philip; Buitelaar, Jan; Franke, Barbara; Gill, Michael; Kent, Lindsey; Holmans, Peter; Middleton, Frank; Thapar, Anita; Lesch, Klaus-Peter; Faraone, Stephen V.; Daly, Mark; Nguyen, Thuy Trang; Schafer, Helmut; Steinhausen, Hans-Christoph; Reif, Andreas; Renner, Tobias J.; Romanos, Marcel; Romanos, Jasmin; Warnke, Andreas; Walitza, Susanne; Freitag, Christine; Meyer, Jobst; Palmason, Haukur; Rothenberger, Aribert; Hawi, Ziarih; Sergeant, Joseph; Roeyers, Herbert; Mick, Eric; Biederman, Joseph

2010-01-01

Objective: Although twin and family studies have shown attention-deficit/hyperactivity disorder (ADHD) to be highly heritable, genetic variants influencing the trait at a genome-wide significant level have yet to be identified. Thus additional genome-wide association studies (GWAS) are needed. Method: We used case-control analyses of 896 cases…

Nested case-control studies: should one break the matching?

PubMed

Borgan, Ørnulf; Keogh, Ruth

2015-10-01

In a nested case-control study, controls are selected for each case from the individuals who are at risk at the time at which the case occurs. We say that the controls are matched on study time. To adjust for possible confounding, it is common to match on other variables as well. The standard analysis of nested case-control data is based on a partial likelihood which compares the covariates of each case to those of its matched controls. It has been suggested that one may break the matching of nested case-control data and analyse them as case-cohort data using an inverse probability weighted (IPW) pseudo likelihood. Further, when some covariates are available for all individuals in the cohort, multiple imputation (MI) makes it possible to use all available data in the cohort. In the paper we review the standard method and the IPW and MI approaches, and compare their performance using simulations that cover a range of scenarios, including one and two endpoints.

Association between Use of Exogenous Testosterone Therapy and Risk of Venous Thrombotic Events among Exogenous Testosterone Treated and Untreated Men with Hypogonadism.

PubMed

Li, Hu; Benoit, Karin; Wang, Wei; Motsko, Stephen

2016-04-01

Limited information exists about whether exogenous testosterone therapy is associated with a risk of venous thrombotic events. We investigated via cohort and nested case-control analyses whether exogenous testosterone therapy is associated with the risk of venous thrombotic events in men with hypogonadism. Databases were reviewed to identify men prescribed exogenous testosterone therapy and/or men with a hypogonadism diagnosis. Propensity score 1:1 matching was used to select patients for cohort analysis. Cases (men with venous thrombotic events) were matched 1:4 with controls (men without venous thrombotic events) for the nested case-control analysis. Primary outcome was defined as incident idiopathic venous thrombotic events. Cox regression and conditional logistic regression were used to assess HRs and ORs, respectively. Sensitivity analyses were also performed. A total of 102,650 exogenous testosterone treated and 102,650 untreated patients were included in cohort analysis after matching, and 2,785 cases and 11,119 controls were included in case-control analysis. Cohort analysis revealed a HR of 1.08 for all testosterone treated patients (95% CI 0.91, 1.27, p = 0.378). Case-control analysis resulted in an OR of 1.02 (95% CI 0.92, 1.13, p = 0.702) for current exogenous testosterone therapy exposure and an OR of 0.92 (95% CI 0.82, 1.03, p = 0.145) for past exogenous testosterone therapy exposure. These results remained nonstatistically significant after stratifying by exogenous testosterone therapy administration route and age category. Most sensitivity analyses yielded consistent results. No significant association was found between exogenous testosterone therapy and incidents of idiopathic or overall venous thrombotic events in men with hypogonadism. However, some discrepant findings exist for the association between injectable formulations and the risk of overall venous thrombotic events. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Prevalence of radiographic hip osteoarthritis is increased in high bone mass.

PubMed

Hardcastle, S A; Dieppe, P; Gregson, C L; Hunter, D; Thomas, G E R; Arden, N K; Spector, T D; Hart, D J; Laugharne, M J; Clague, G A; Edwards, M H; Dennison, E M; Cooper, C; Williams, M; Davey Smith, G; Tobias, J H

2014-08-01

Epidemiological studies have shown an association between increased bone mineral density (BMD) and osteoarthritis (OA), but whether this represents cause or effect remains unclear. In this study, we used a novel approach to investigate this question, determining whether individuals with High Bone Mass (HBM) have a higher prevalence of radiographic hip OA compared with controls. HBM cases came from the UK-based HBM study: HBM was defined by BMD Z-score. Unaffected relatives of index cases were recruited as family controls. Age-stratified random sampling was used to select further population controls from the Chingford and Hertfordshire cohort studies. Pelvic radiographs were pooled and assessed by a single observer blinded to case-control status. Analyses used logistic regression, adjusted for age, gender and body mass index (BMI). 530 HBM hips in 272 cases (mean age 62.9 years, 74% female) and 1702 control hips in 863 controls (mean age 64.8 years, 84% female) were analysed. The prevalence of radiographic OA, defined as Croft score ≥3, was higher in cases compared with controls (20.0% vs 13.6%), with adjusted odds ratio (OR) [95% CI] 1.52 [1.09, 2.11], P = 0.013. Osteophytes (OR 2.12 [1.61, 2.79], P < 0.001) and subchondral sclerosis (OR 2.78 [1.49, 5.18], P = 0.001) were more prevalent in cases. However, no difference in the prevalence of joint space narrowing (JSN) was seen (OR 0.97 [0.72, 1.33], P = 0.869). An increased prevalence of radiographic hip OA and osteophytosis was observed in HBM cases compared with controls, in keeping with a positive association between HBM and OA and suggesting that OA in HBM has a hypertrophic phenotype. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

HIV enteropathy: crypt stem and transit cell hyperproliferation induces villous atrophy in HIV/Microsporidia-infected jejunal mucosa.

PubMed

Batman, Philip A; Kotler, Donald P; Kapembwa, Moses S; Booth, Dawn; Potten, Christopher S; Orenstein, Jan M; Scally, Andrew J; Griffin, George E

2007-02-19

The study aim was to analyse the kinetics of stem and transit cells in the crypts of jejunal mucosa infected with HIV and Microsporidia. The size of villi, depth of crypts and proliferative activity of transit and stem cells in jejunal mucosa were measured using morphometric techniques. The surface area/volume ratio (S/V) of jejunal biopsies was estimated under light microscopy using a Weibel graticule. Crypt length was measured by counting enterocytes along the crypt side from the base to the villus junction, and the mean crypt length was calculated. The S/V and crypt lengths of the jejunal mucosa of 21 HIV and Microsporidia-infected test cases were compared with 14 control cases. The labelling index in relation to the crypt cell position of 10 of the test cases was analysed compared with 13 control cases. Differences were found in the S/V and crypt length, and there was a negative correlation between S/V and crypt length in test and control cases combined. Cell labelling indices fell into low and high proliferation groups. There were significant differences in labelling indices between low proliferation test cases and controls, between high proliferation test cases and controls, and between high and low proliferation test cases. Villous atrophy induced by HIV and Microsporidia is attributed to crypt cell hyperplasia and the encroachment of crypt cells onto villi. These infections induce crypt hypertrophy by stimulating cell mitosis predominantly in transit cells but also in stem cells. Increased stem cell proliferation occurs only in high proliferation cases.

The effect of holes in long-lasting insecticidal nets on malaria in Malawi: results from a case-control study.

PubMed

Minta, Anna A; Landman, Keren Z; Mwandama, Dyson A; Shah, Monica P; Eng, Jodi L Vanden; Sutcliffe, James F; Chisaka, Joseph; Lindblade, Kim A; Mathanga, Don P; Steinhardt, Laura C

2017-10-02

Long-lasting insecticidal nets (LLINs) are a cornerstone of malaria prevention. Holes develop in LLINs over time and compromise their physical integrity, but how holes affect malaria transmission risk is not well known. After a nationwide mass LLIN distribution in July 2012, a study was conducted to assess the relationship between LLIN damage and malaria. From March to September 2013, febrile children ages 6-59 months who consistently slept under LLINs (every night for 2 weeks before illness onset) were enrolled in a case-control study at Machinga District Hospital outpatient department. Cases were positive for Plasmodium falciparum asexual parasites by microscopy while controls were negative. Digital photographs of participants' LLINs were analysed using an image-processing programme to measure holes. Total hole area was classified by quartiles and according to the World Health Organization's proportionate hole index (pHI) cut-offs [< 79 cm 2 (good), 80-789 cm 2 (damaged), and > 790 cm 2 (too torn)]. Number of holes by location and size, and total hole area, were compared between case and control LLINs using non-parametric analyses and logistic regression. Of 248 LLINs analysed, 97 (39%) were from cases. Overall, 86% of LLINs had at least one hole. The median number of holes of any size was 9 [interquartile range (IQR) 3, 22], and most holes were located in the lower halves of the nets [median 7 (IQR 2, 16)]. There were no differences in number or location of holes between LLINs used by cases and controls. The median total hole area was 10 cm 2 (IQR 2, 125) for control LLINs and 8 cm 2 (IQR 2, 47) for case LLINs (p = 0.10). Based on pHI, 109 (72%) control LLINs and 83 (86%) case LLINs were in "good" condition. Multivariable modeling showed no association between total hole area and malaria, controlling for child age, caregiver education, and iron versus thatched roof houses. LLIN holes were not associated with increased odds of malaria in this study. However, most of the LLINs were in relatively good condition 1 year after distribution. Future studies should examine associations between LLIN holes and malaria risk with more damaged nets.

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

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.

Should Controls With Respiratory Symptoms Be Excluded From Case-Control Studies of Pneumonia Etiology? Reflections From the PERCH Study

PubMed Central

Hammitt, Laura L.; Deloria Knoll, Maria; Baggett, Henry C.; Brooks, W. Abdullah; Howie, Stephen R. C.; Kotloff, Karen L.; Levine, Orin S.; Madhi, Shabir A.; Murdoch, David R.; Scott, J. Anthony G.; Thea, Donald M.; Driscoll, Amanda J.; Karron, Ruth A.; Park, Daniel E.; Prosperi, Christine; Zeger, Scott L.; O’Brien, Katherine L.; Feikin, Daniel R.; O’Brien, Katherine L.; Levine, Orin S.; Knoll, Maria Deloria; Feikin, Daniel R.; DeLuca, Andrea N.; Driscoll, Amanda J.; Fu, Wei; Hammitt, Laura L.; Higdon, Melissa M.; Kagucia, E. Wangeci; Karron, Ruth A.; Li, Mengying; Park, Daniel E.; Prosperi, Christine; Wu, Zhenke; Zeger, Scott L.; Watson, Nora L.; Crawley, Jane; Murdoch, David R.; Brooks, W. Abdullah; Endtz, Hubert P.; Zaman, Khalequ; Goswami, Doli; Hossain, Lokman; Jahan, Yasmin; Ashraf, Hasan; Howie, Stephen R. C.; Ebruke, Bernard E.; Antonio, Martin; McLellan, Jessica; Machuka, Eunice; Shamsul, Arifin; Zaman, Syed M.A.; Mackenzie, Grant; Scott, J. Anthony G.; Awori, Juliet O.; Morpeth, Susan C.; Kamau, Alice; Kazungu, Sidi; Kotloff, Karen L.; Tapia, Milagritos D.; Sow, Samba O.; Sylla, Mamadou; Tamboura, Boubou; Onwuchekwa, Uma; Kourouma, Nana; Toure, Aliou; Madhi, Shabir A.; Moore, David P.; Adrian, Peter V.; Baillie, Vicky L.; Kuwanda, Locadiah; Mudau, Azwifarwi; Groome, Michelle J.; Baggett, Henry C.; Thamthitiwat, Somsak; Maloney, Susan A.; Bunthi, Charatdao; Rhodes, Julia; Sawatwong, Pongpun; Akarasewi, Pasakorn; Thea, Donald M.; Mwananyanda, Lawrence; Chipeta, James; Seidenberg, Phil; Mwansa, James; wa Somwe, Somwe; Kwenda, Geoffrey

2017-01-01

Abstract Many pneumonia etiology case-control studies exclude controls with respiratory illness from enrollment or analyses. Herein we argue that selecting controls regardless of respiratory symptoms provides the least biased estimates of pneumonia etiology. We review 3 reasons investigators may choose to exclude controls with respiratory symptoms in light of epidemiologic principles of control selection and present data from the Pneumonia Etiology Research for Child Health (PERCH) study where relevant to assess their validity. We conclude that exclusion of controls with respiratory symptoms will result in biased estimates of etiology. Randomly selected community controls, with or without respiratory symptoms, as long as they do not meet the criteria for case-defining pneumonia, are most representative of the general population from which cases arose and the least subject to selection bias. PMID:28575354

A Case Control Study of Suicide and Attempted Suicide in Older Adults.

ERIC Educational Resources Information Center

Beautrais, Annette L.

2002-01-01

Risk factors for serious suicidal behavior among older adults were examined in a case control study of adults aged 55 and older who died by suicide or made suicide attempts and who were compared with randomly selected comparison subjects. Multivariate analyses suggested that mood disorders were the most significant risk factor for suicidal…

Impact of organised mammography screening on breast cancer mortality in a case–control and cohort study

PubMed Central

Heinävaara, Sirpa; Sarkeala, Tytti; Anttila, Ahti

2016-01-01

Background: The usefulness of case–control studies has been questioned. Our aim was to evaluate the long-term effect of screening on breast cancer mortality within the population-based mammography programme in Finland using a case–control design, and to compare the analyses with the earlier cohort study. Methods: The cases were women invited to screening, diagnosed and died from breast cancer in 1992–2011 while being 50–84 years at death. We chose 10 controls for each case with non-restrictive eligibility criteria. Our data included 1907 cases and 18 978 matched controls. We analysed associations between the screening participation and the risk of breast cancer death using the conditional Cox proportional hazards model. The effect estimates were corrected for self-selection bias. Results: An overall effect of screening was 0.67 (95% confidence interval (CI): 0.49–0.90), and that remained unchanged over time. Analyses with matching criteria comparable to the cohort study yielded an effect (0.70, 95% CI: 0.49–1.00) in 1992–2003 similar to that of the previous cohort analysis (0.72, 95% CI: 0.56–0.88). Conclusions: Organised mammography screening decreases mortality from breast cancer by 33% among the participants. If made comparable, a case–cohort study can yield effect estimates similar to a cohort study. PMID:27010748

NEK1 variants confer susceptibility to amyotrophic lateral sclerosis

PubMed Central

Kenna, Kevin P; van Doormaal, Perry T C; Dekker, Annelot M; Ticozzi, Nicola; Kenna, Brendan J; Diekstra, Frank P; van Rheenen, Wouter; van Eijk, Kristel R; Jones, Ashley R; Keagle, Pamela; Shatunov, Aleksey; Sproviero, William; Smith, Bradley N; van Es, Michael A; Topp, Simon D; Kenna, Aoife; Miller, Jack W; Fallini, Claudia; Tiloca, Cinzia; McLaughlin, Russell L; Vance, Caroline; Troakes, Claire; Colombrita, Claudia; Mora, Gabriele; Calvo, Andrea; Verde, Federico; Al-Sarraj, Safa; King, Andrew; Calini, Daniela; de Belleroche, Jacqueline; Baas, Frank; van der Kooi, Anneke J; de Visser, Marianne; Asbroek, Anneloor L M A ten; Sapp, Peter C; McKenna-Yasek, Diane; Polak, Meraida; Asress, Seneshaw; Muñoz-Blanco, José Luis; Strom, Tim M; Meitinger, Thomas; Morrison, Karen E; Lauria, Giuseppe; Williams, Kelly L; Leigh, P Nigel; Nicholson, Garth A; Blair, Ian P; Leblond, Claire S; Dion, Patrick A; Rouleau, Guy A; Pall, Hardev; Shaw, Pamela J; Turner, Martin R; Talbot, Kevin; Taroni, Franco; Boylan, Kevin B; Van Blitterswijk, Marka; Rademakers, Rosa; Esteban-Pérez, Jesús; García-Redondo, Alberto; Van Damme, Phillip; Robberecht, Wim; Chio, Adriano; Gellera, Cinzia; Drepper, Carsten; Sendtner, Michael; Ratti, Antonia; Glass, Jonathan D; Mora, Jesús S; Basak, Nazli A; Hardiman, Orla; Ludolph, Albert C; Andersen, Peter M; Weishaupt, Jochen H; Brown, Robert H; Al-Chalabi, Ammar; Silani, Vincenzo; Shaw, Christopher E; van den Berg, Leonard H; Veldink, Jan H; Landers, John E

2017-01-01

To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology. PMID:27455347

Long-term mobile phone use and acoustic neuroma risk.

PubMed

Pettersson, David; Mathiesen, Tiit; Prochazka, Michaela; Bergenheim, Tommy; Florentzson, Rut; Harder, Henrik; Nyberg, Gunnar; Siesjö, Peter; Feychting, Maria

2014-03-01

There is concern about potential effects of radiofrequency fields generated by mobile phones on cancer risk. Most previous studies have found no association between mobile phone use and acoustic neuroma, although information about long-term use is limited. We conducted a population-based, nation-wide, case-control study of acoustic neuroma in Sweden. Eligible cases were persons aged 20 to 69 years, who were diagnosed between 2002 and 2007. Controls were randomly selected from the population registry, matched on age, sex, and residential area. Postal questionnaires were completed by 451 cases (83%) and 710 controls (65%). Ever having used mobile phones regularly (defined as weekly use for at least 6 months) was associated with an odds ratio (OR) of 1.18 (95% confidence interval = 0.88 to 1.59). The association was weaker for the longest induction time (≥10 years) (1.11 [0.76 to 1.61]) and for regular use on the tumor side (0.98 [0.68 to 1.43]). The OR for the highest quartile of cumulative calling time (≥680 hours) was 1.46 (0.98 to 2.17). Restricting analyses to histologically confirmed cases reduced all ORs; the OR for ≥680 hours was 1.14 (0.63 to 2.07). A similar pattern was seen for cordless land-line phones, although with slightly higher ORs. Analyses of the complete history of laterality of mobile phone revealed considerable bias in laterality analyses. The findings do not support the hypothesis that long-term mobile phone use increases the risk of acoustic neuroma. The study suggests that phone use might increase the likelihood that an acoustic neuroma case is detected and that there could be bias in the laterality analyses performed in previous studies.

BIOMONITORING TO ACHIEVE CONTROL OF TOXIC EFFLUENTS

EPA Science Inventory

This 48 - page Technology Transfer Report provides a case study of how water quality-based toxicity control procedures can be combined with chemical analyses and biological stream surveys to achieve more effective water pollution control. t describes how regulatory agencies used ...

Comparative analysis of bones, mites, soil chemistry, nematodes and soil micro-eukaryotes from a suspected homicide to estimate the post-mortem interval.

PubMed

Szelecz, Ildikó; Lösch, Sandra; Seppey, Christophe V W; Lara, Enrique; Singer, David; Sorge, Franziska; Tschui, Joelle; Perotti, M Alejandra; Mitchell, Edward A D

2018-01-08

Criminal investigations of suspected murder cases require estimating the post-mortem interval (PMI, or time after death) which is challenging for long PMIs. Here we present the case of human remains found in a Swiss forest. We have used a multidisciplinary approach involving the analysis of bones and soil samples collected beneath the remains of the head, upper and lower body and "control" samples taken a few meters away. We analysed soil chemical characteristics, mites and nematodes (by microscopy) and micro-eukaryotes (by Illumina high throughput sequencing). The PMI estimate on hair 14 C-data via bomb peak radiocarbon dating gave a time range of 1 to 3 years before the discovery of the remains. Cluster analyses for soil chemical constituents, nematodes, mites and micro-eukaryotes revealed two clusters 1) head and upper body and 2) lower body and controls. From mite evidence, we conclude that the body was probably brought to the site after death. However, chemical analyses, nematode community analyses and the analyses of micro-eukaryotes indicate that decomposition took place at least partly on site. This study illustrates the usefulness of combining several lines of evidence for the study of homicide cases to better calibrate PMI inference tools.

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.

XPAT: a toolkit to conduct cross-platform association studies with heterogeneous sequencing datasets.

PubMed

Yu, Yao; Hu, Hao; Bohlender, Ryan J; Hu, Fulan; Chen, Jiun-Sheng; Holt, Carson; Fowler, Jerry; Guthery, Stephen L; Scheet, Paul; Hildebrandt, Michelle A T; Yandell, Mark; Huff, Chad D

2018-04-06

High-throughput sequencing data are increasingly being made available to the research community for secondary analyses, providing new opportunities for large-scale association studies. However, heterogeneity in target capture and sequencing technologies often introduce strong technological stratification biases that overwhelm subtle signals of association in studies of complex traits. Here, we introduce the Cross-Platform Association Toolkit, XPAT, which provides a suite of tools designed to support and conduct large-scale association studies with heterogeneous sequencing datasets. XPAT includes tools to support cross-platform aware variant calling, quality control filtering, gene-based association testing and rare variant effect size estimation. To evaluate the performance of XPAT, we conducted case-control association studies for three diseases, including 783 breast cancer cases, 272 ovarian cancer cases, 205 Crohn disease cases and 3507 shared controls (including 1722 females) using sequencing data from multiple sources. XPAT greatly reduced Type I error inflation in the case-control analyses, while replicating many previously identified disease-gene associations. We also show that association tests conducted with XPAT using cross-platform data have comparable performance to tests using matched platform data. XPAT enables new association studies that combine existing sequencing datasets to identify genetic loci associated with common diseases and other complex traits.

Should Controls With Respiratory Symptoms Be Excluded From Case-Control Studies of Pneumonia Etiology? Reflections From the PERCH Study.

PubMed

Higdon, Melissa M; Hammitt, Laura L; Deloria Knoll, Maria; Baggett, Henry C; Brooks, W Abdullah; Howie, Stephen R C; Kotloff, Karen L; Levine, Orin S; Madhi, Shabir A; Murdoch, David R; Scott, J Anthony G; Thea, Donald M; Driscoll, Amanda J; Karron, Ruth A; Park, Daniel E; Prosperi, Christine; Zeger, Scott L; O'Brien, Katherine L; Feikin, Daniel R

2017-06-15

Many pneumonia etiology case-control studies exclude controls with respiratory illness from enrollment or analyses. Herein we argue that selecting controls regardless of respiratory symptoms provides the least biased estimates of pneumonia etiology. We review 3 reasons investigators may choose to exclude controls with respiratory symptoms in light of epidemiologic principles of control selection and present data from the Pneumonia Etiology Research for Child Health (PERCH) study where relevant to assess their validity. We conclude that exclusion of controls with respiratory symptoms will result in biased estimates of etiology. Randomly selected community controls, with or without respiratory symptoms, as long as they do not meet the criteria for case-defining pneumonia, are most representative of the general population from which cases arose and the least subject to selection bias. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Depressive symptoms in HIV-infected and seronegative control subjects in Cameroon: Effect of age, education and gender

PubMed Central

Kanmogne, Georgette D.; Qiu, Fang; Ntone, Félicien E.; Fonsah, Julius Y.; Njamnshi, Dora M.; Kuate, Callixte T.; Doh, Roland F.; Kengne, Anne M.; Tagny, Claude T.; Nchindap, Emilienne; Kenmogne, Léopoldine; Mbanya, Dora; Cherner, Mariana; Heaton, Robert K.; Njamnshi, Alfred K.

2017-01-01

Depression is a leading cause of HIV/AIDS disease burden; it worsens health outcomes and quality of life. Addressing this problem requires accurate quantification of the extra burden of depression to HIV/AIDS in a given population, and knowledge of the baseline depression prevalence in the general population. There has been no previous study of depression in the general Cameroonian population. The current study attempts to address that important need. We used the Beck Depression Inventory-II to assess the prevalence and severity of depressive symptoms in 270 HIV-infected and seronegative Cameroonians. Univariate analyses showed a trend toward higher depressive symptoms among cases, compared to controls (p = 0.055), and among older subjects (>40 years), compared to younger subjects (≤40 years) (p = 0.059). Analysis of depression severity showed that 33.73% of cases had moderate-to-severe depressive symptoms, compared to 19.8% of controls (p<0.01). However, multivariable negative binomial regression analyses showed no effect of age, HIV status, CD4 levels, viral loads, ART, or opportunistic infections on the risk of depressive symptoms. Both univariate and multivariable regression analyses showed significantly higher risk of depressive symptoms among females compared to males; this was significant for both female controls and female cases. Female cases had significantly higher CD4 cell counts and lower viral loads, compared to males. Both univariate and multivariable regression analyses showed that lower education (≤10 years) was associated with increased risk of depressive symptoms. This study shows a high prevalence of depressive symptoms among seronegative controls and HIV-infected Cameroonians. Integrating care for mental disorders such as depression into primary health care and existing HIV/AIDS treatment programs in Cameroon may improve the wellbeing of the general population and could lower the HIV/AIDS burden. PMID:28231258

Depressive symptoms in HIV-infected and seronegative control subjects in Cameroon: Effect of age, education and gender.

PubMed

Kanmogne, Georgette D; Qiu, Fang; Ntone, Félicien E; Fonsah, Julius Y; Njamnshi, Dora M; Kuate, Callixte T; Doh, Roland F; Kengne, Anne M; Tagny, Claude T; Nchindap, Emilienne; Kenmogne, Léopoldine; Mbanya, Dora; Cherner, Mariana; Heaton, Robert K; Njamnshi, Alfred K

2017-01-01

Depression is a leading cause of HIV/AIDS disease burden; it worsens health outcomes and quality of life. Addressing this problem requires accurate quantification of the extra burden of depression to HIV/AIDS in a given population, and knowledge of the baseline depression prevalence in the general population. There has been no previous study of depression in the general Cameroonian population. The current study attempts to address that important need. We used the Beck Depression Inventory-II to assess the prevalence and severity of depressive symptoms in 270 HIV-infected and seronegative Cameroonians. Univariate analyses showed a trend toward higher depressive symptoms among cases, compared to controls (p = 0.055), and among older subjects (>40 years), compared to younger subjects (≤40 years) (p = 0.059). Analysis of depression severity showed that 33.73% of cases had moderate-to-severe depressive symptoms, compared to 19.8% of controls (p<0.01). However, multivariable negative binomial regression analyses showed no effect of age, HIV status, CD4 levels, viral loads, ART, or opportunistic infections on the risk of depressive symptoms. Both univariate and multivariable regression analyses showed significantly higher risk of depressive symptoms among females compared to males; this was significant for both female controls and female cases. Female cases had significantly higher CD4 cell counts and lower viral loads, compared to males. Both univariate and multivariable regression analyses showed that lower education (≤10 years) was associated with increased risk of depressive symptoms. This study shows a high prevalence of depressive symptoms among seronegative controls and HIV-infected Cameroonians. Integrating care for mental disorders such as depression into primary health care and existing HIV/AIDS treatment programs in Cameroon may improve the wellbeing of the general population and could lower the HIV/AIDS burden.

Study design and hierarchy of evidence for surgical decision making.

PubMed

Sprague, Sheila; McKay, Paula; Thoma, Achilleas

2008-04-01

This article provides a historical overview of the hierarchy of evidence for surgical decision making and discusses key study designs in the hierarchy of evidence. This encompasses meta-analyses, randomized controlled trials, and observational studies, including cohort and case-controlled studies, case series and case reports, and basic science studies. This article also reviews the principles and importance of evidence-based plastic surgery and describes several systems to rate the strength of the scientific evidence.

Occupational risk factors for Wilms' tumor

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

Bunin, G.; Kramer, S.; Nass, C.

A matched case-control study of Wilms' tumor investigated parental occupational risk factors. Cases diagnosed in 1970-1983 were identified through a population-based tumor registry and hospital registries in the Greater Philadelphia area. Controls were selected by random digit dialing and were matched to cases on race, birth date (+/- 3 years), and the area code and exchange of the case's telephone number at diagnosis. Parents of 100 matched pairs were interviewed by telephone. Parents of patients and controls were generally similar in demographic characteristics, except that mothers differed in religion. Published schemes were used to group jobs into clusters of similarmore » exposures and to determine exposures from industry and job title. Analyses were done for preconception, pregnancy, and postnatal time periods. More case than control fathers had jobs in a cluster that includes machinists and welders (odds ratios (ORs) = 4.0-5.7, p less than or equal to 0.04). Paternal exposures to lead, silver, tin, and iron (some exposures of this cluster) were associated with Wilms' tumor in some analyses, with moderate odds ratios (ORs = 1.5-3.4). In general, the highest odds ratios were found for the preconception period among the genetic (prezygotic) cases. No maternal job clusters or exposures gave significantly elevated odds ratios. These results support a previous finding that lead is a risk factor, but not radiation, hydrocarbon, or boron exposures.« less

Potential Psychosocial Risk Factors for Chronic TMD: Descriptive Data and Empirically Identified Domains from the OPPERA Case-Control Study

PubMed Central

Fillingim, Roger B.; Ohrbach, Richard; Greenspan, Joel D.; Knott, Charles; Dubner, Ronald; Bair, Eric; Baraian, Cristina; Slade, Gary D.; Maixner, William

2011-01-01

Case-control studies have consistently associated psychosocial factors with chronic pain in general, and with temporomandibular disorders (TMD) specifically. Moreover, a handful of prospective studies suggest that pre-existing psychosocial characteristics represent risk factors for new onset TMD. The current study presents psychosocial findings from the baseline case-control study of the Orofacial Pain Prospective Evaluation and Risk Assessment (OPPERA) cooperative agreement. For this study, 1,633 TMD-free controls and 185 TMD cases completed a battery of psychosocial instruments assessing general psychosocial adjustment and personality, affective distress, psychosocial stress, somatic awareness, and pain coping and catastrophizing. In bivariate and demographically-adjusted analyses, odds of TMD were associated with higher levels of psychosocial symptoms, affective distress, somatic awareness, and pain catastrophizing. Among controls, significant gender and ethnic group differences in psychosocial measures were observed, consistent with previous findings. Principal component analysis was undertaken to identify latent constructs revealing four components: stress and negative affectivity, global psychosocial symptoms, passive pain coping, and active pain coping. These findings provide further evidence of associations between psychosocial factors and TMD. Future prospective analyses in the OPPERA cohort will determine if the premorbid presence of these psychosocial factors predicts increased risk for developing new-onset TMD. PMID:22074752

Fetal Growth and Childhood Acute Lymphoblastic Leukemia: Findings from the Childhood Leukemia International Consortium (CLIC)

PubMed Central

Milne, Elizabeth; Greenop, Kathryn R.; Metayer, Catherine; Schüz, Joachim; Petridou, Eleni; Pombo-de-Oliveira, Maria S.; Infante-Rivard, Claire; Roman, Eve; Dockerty, John D.; Spector, Logan G.; Koifman, Sérgio; Orsi, Laurent; Rudant, Jérémie; Dessypris, Nick; Simpson, Jill; Lightfoot, Tracy; Kaatsch, Peter; Baka, Margarita; Faro, Alessandra; Armstrong, Bruce K.; Clavel, Jacqueline; Buffler, Patricia A.

2013-01-01

Positive associations have been reported between measures of accelerated fetal growth and risk of childhood acute lymphoblastic leukemia (ALL). We investigated this association by pooling individual-level data from 12 case-control studies participating in the Childhood Leukemia International Consortium. Two measures of fetal growth – weight-for-gestational-age and proportion of optimal birth weight (POBW) – were analysed. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression, and combined in fixed effects meta-analyses. Pooled analyses of all data were also undertaken using multivariable logistic regression. Subgroup analyses were undertaken when possible. Data on weight for gestational age were available for 7,348 cases and 12,489 controls from all 12 studies and POBW data were available for 1,680 cases and 3,139 controls from three studies. The summary ORs from the meta-analyses were 1.24 (95% CI 1.13, 1.36) for children who were large for gestational age relative to appropriate for gestational age, and 1.16 (95% CI: 1.09, 1.24) for a one standard deviation increase in POBW. The pooled analyses produced similar results. The summary and pooled ORs for small-for-gestational-age children were 0.83 (95% CI: 0.75, 0.92) and 0.86 (95% CI 0.77, 0.95) respectively. Results were consistent across subgroups defined by sex, ethnicity and immunophenotype, and when the analysis was restricted to children who did not have high birth weight. The evidence that accelerated fetal growth is associated with a modest increased risk of childhood ALL is strong and consistent with known biological mechanisms involving insulin like growth factors. PMID:23754574

Association between statin therapy and tendon rupture: a case-control study.

PubMed

Beri, Abhimanyu; Dwamena, Francesca C; Dwamena, Ben A

2009-05-01

Although case reports of a possible association between statin therapy and tendon rupture have been published, no analytical studies exploring this relationship have been reported. We conducted a case-control study using the electronic medical records at Michigan State University from 2002 to 2007 to assess whether statin use is a risk factor for tendon rupture. We compared exposure to statins in 93 cases of tendon rupture with similar exposure in 279 sex- and age-matched controls. Exposure to statins was defined as documentation in the electronic medical record of statin use in the 12 months preceding tendon rupture. For controls, the exposure period was defined as 1 year preceding the last office visit. We used a multivariate logistic regression model, controlling for diabetes, renal disease, rheumatologic disease, and steroid use, to calculate the adjusted odds ratios (ORs). There was no significant difference between cases and controls in the rates of statin use, with either univariate [OR = 1.0, 95% confidence interval (CI) 0.54-1.84] or multivariate analyses (OR = 1.10, 95% CI 0.57-2.13). Based on predetermined subgroup analyses, statin exposure was found to be a significant risk factor for tendon rupture in women (adjusted OR = 3.76, 95% CI 1.11-12.75) but not in men (adjusted OR = 0.66, 95% CI 0.29-1.51). In conclusion, we found no overall association between statin use and tendon rupture, but subgroup analysis suggested that women with tendon rupture were more likely to be on statins.

Progranulin gene variation affects serum progranulin levels differently in Danish bipolar individuals compared with healthy controls.

PubMed

Buttenschøn, Henriette N; Nielsen, Marit N; Thotakura, Gangadaar; Lee, Chris W; Nykjær, Anders; Mors, Ole; Glerup, Simon

2017-06-01

The identification of peripheral biomarkers for bipolar disorder is of great importance and has the potential to improve diagnosis, treatment and prognosis. Recent studies have reported lower plasma progranulin levels in bipolar individuals compared with controls and association with single nucleotide polymorphisms (SNPs) within the progranulin gene (GRN). In the present study, we investigated the effect of GRN and sortilin (SORT1) gene variation on serum progranulin levels in bipolar individuals and controls. In a Danish cohort of individuals with bipolar disorder and controls, we analysed the serum progranulin level (nbipolar=80, ncontrols=76) and five SNPs located within GRN and two SNPs near the SORT1 gene encoding sortilin, a progranulin scavenger receptor known to affect circulating progranulin levels (nbipolar=166, ncontrols=186). We observed no significant difference in the serum progranulin level between cases and controls and none of the analysed SNPs located within GRN or close to SORT1 were associated with bipolar disorder. Crude and adjusted (adjusted for case-control status, sex and age) linear regression analyses showed no effect of any SNPs on the serum progranulin level. However, we observed that the mean serum progranulin level in cases and controls is affected differently depending on the genotypes of two SNPs within GRN (rs2879096 and rs4792938). The sample size is relatively small and detailed information on medication and polarity of the disorder is not available. No correction for multiple testing was performed. Our study suggests that the potential of progranulin as a biomarker for bipolar disorder is genotype dependent.

Coffee, decaffeinated coffee, tea and cancer of the colon and rectum: a review of epidemiological studies, 1990-2003.

PubMed

Tavani, Alessandra; La Vecchia, Carlo

2004-10-01

The literature from 1990 to 2003 on the relation between coffee, decaffeinated coffee, tea and colorectal cancer risk has been reviewed. For the relation with coffee, three cohort (517 total cases) and nine case-control studies (7555 cases) analysed colon cancer; three cohort (307 cases) and four case-control studies (2704 cases) rectal cancer; six case-control studies (854 cases) colorectal cancer. For colon cancer most case-control studies found risk estimates below unity; the results are less clear for cohort studies. No relation emerged for rectal cancer. A meta-analysis, including five cohort and twelve case-control studies, reported a pooled relative risk of 0.76 (significant). Any methodological artefact is unlikely to account for the consistent inverse association in different countries and settings. Plausible biological explanations include coffee-related reductions of cholesterol, bile acids and neutral sterol secretion in the colon; antimutagenic properties of selected coffee components; increased colonic motility. Decaffeinated coffee was not related to either colon or rectal cancer in three case-control studies. No overall association between tea and either colon or rectal cancer risk emerged in seven cohort (1756 total cases of colon, 759 of rectal and 60 of colorectal cancer) and 12 case-control studies (8058 cases of colon, 4865 of rectal, 604 of colorectal cancer).

Case-control study of childhood acute lymphoblastic leukemia and residential radon exposure.

PubMed

Lubin, J H; Linet, M S; Boice, J D; Buckley, J; Conrath, S M; Hatch, E E; Kleinerman, R A; Tarone, R E; Wacholder, S; Robison, L L

1998-02-18

Several ecologic analyses have shown significant positive associations between mean indoor radon concentrations and risk of leukemia at all ages (acute myeloid leukemia and chronic lymphocytic leukemia) and for children (all leukemia, acute myeloid leukemia, and acute lymphoblastic leukemia [ALL]). As part of an age-matched, case-control study of childhood ALL in the United States, we investigated the association between the incidence of ALL in children under age 15 years and indoor radon exposure. Radon detectors were placed in current and previous homes of subjects where they resided for 6 months or longer. Children were included in analyses if radon measurements covered 70% or more of the 5-year period prior to diagnosis for case subjects (or from birth for case subjects under age 5 years) and the corresponding reference dates for control subjects. Radon levels could be estimated for 97% of the exposure period for the eligible 505 case subjects and 443 control subjects. Mean radon concentration was lower for case subjects (65.4 becquerels per cubic meter [Bqm(-3)]) than for control subjects (79.1 Bqm(-3)). For categories less than 37, 37-73, 74-147, and 148 or more Bqm(-3) of radon exposure, relative risks based on matched case-control pairs were 1.00, 1.22, 0.82, and 1.02, respectively, and were similar to results from an unmatched analysis. There was no association between ALL and radon exposure within subgroups defined by categories of age, income, birth order, birth weight, sex, type of residence, magnetic field exposure, parental age at the subject's birth, parental occupation, or parental smoking habits. In contrast to prior ecologic studies, the results from this analytic study provide no evidence for an association between indoor radon exposure and childhood ALL.

A Pilot Study to Evaluate the Oral Microbiome and Dental Health in Primary Open-Angle Glaucoma.

PubMed

Polla, Daniel; Astafurov, Konstantin; Hawy, Eman; Hyman, Leslie; Hou, Wei; Danias, John

2017-04-01

To evaluate possible associations between primary open-angle glaucoma (POAG), dental health, and the oral microbiome. Case-control study was conducted at SUNY Downstate. Adult subjects (40 to 87 y) were recruited as POAG cases (n=119) and controls without glaucoma (n=78) based on visual field and optic nerve criteria. Overall 74.6% were African Americans (AA). Information on medical history and oral health was collected and ophthalmologic examinations were performed. Mouthwash specimens (28 AA cases and 17 controls) were analyzed for bacterial DNA amounts. Analyses were limited to AAs as the predominant racial group. Outcome measures included number of natural teeth, self-reported periodontal health parameters, and amounts and prevalence of oral bacterial species. Logistic regression was used to evaluate associated factors and potential interactions. Cases and controls had similar age (mean: 62.2 and 60.9 y, respectively, P>0.48), and frequency of hypertension, diabetes, but cases had a higher proportion of men (P<0.04). On average (±SD), cases had fewer natural teeth than controls [18.0 (±11.1) vs. 20.7 (±9.4)]. Having more natural teeth was inversely associated with POAG, in multivariable analyses, at older ages [eg, odds ratio (95% confidence interval) at age 55: 1.0 (0.95-1.06), P=0.98 vs. at age 85: 0.87 (0.79-0.96), P=0.007]. Amounts of Streptococci were higher in cases than controls (P<0.03) in samples from the subset of subjects analyzed. The number of teeth (an oral health indicator) and alterations in the amounts of oral bacteria may be associated with glaucoma pathology. Further investigation of the association between dental health and glaucoma is warranted.

Analgesics use and ESRD in younger age: a case-control study

PubMed Central

van der Woude, Fokke J; Heinemann, Lothar AJ; Graf, Helmut; Lewis, Michael; Moehner, Sabine; Assmann, Anita; Kühl-Habich, Doerthe

2007-01-01

Background An ad hoc peer-review committee was jointly appointed by Drug Authorities and Industry in Germany, Austria and Switzerland in 1999/2000 to review the evidence for a causal relation between phenacetin-free analgesics and nephropathy. The committee found the evidence as inconclusive and requested a new case-control study of adequate design. Methods We performed a population-based case-control study with incident cases of end-stage renal disease (ESRD) under the age of 50 years and four age and sex-matched neighborhood controls in 170 dialysis centers (153 in Germany, and 17 in Austria) from January 1, 2001 to December 31, 2004. Data on lifetime medical history, risk factors, treatment, job exposure and intake of analgesics were obtained in a standardized face-to-face interview using memory aids to enhance accuracy. Study design, study performance, analysis plan, and study report were approved by an independent international advisory committee and by the Drug Authorities involved. Unconditional logistic regression analyses were performed. Results The analysis included 907 cases and 3,622 controls who had never used phenacetin-containing analgesics in their lifetime. The use of high cumulative lifetime dose (3rd tertile) of analgesics in the period up to five years before dialysis was not associated with later ESRD. Adjusted odds ratios with 95% confidence intervals were 0.8 (0.7 – 1.0) and 1.0 (0.8 – 1.3) for ever- compared with no or low use and high use compared with low use, respectively. The same results were found for all analgesics and for mono-, and combination preparations with and without caffeine. No increased risk was shown in analyses stratifying for dose and duration. Dose-response analyses showed that analgesic use was not associated with an increased risk for ESRD up to 3.5 kg cumulative lifetime dose (98 % of the cases with ESRD). While the large subgroup of users with a lifetime dose up to 0.5 kg (278 cases and 1365 controls) showed a significantly decreased risk, a tiny subgroup of extreme users with over 3.5 kg lifetime use (19 cases and 11 controls) showed a significant risk increase. The detailed evaluation of 22 cases and 19 controls with over 2.5 kg lifetime use recommended by the regulatory advisors showed an impressive excess of other conditions than analgesics triggering the evolution of ESRD in cases compared with controls. Conclusion We found no clinically meaningful evidence for an increased risk of ESRD associated with use of phenacetin-free analgesics in single or combined formulation. The apparent risk increase shown in a small subgroup with extreme lifetime dose of analgesics is most likely an indirect, non-causal association. This hypothesis, however, cannot be confirmed or refuted within our case-control study. Overall, our results lend support to the mounting evidence that phenacetin-free analgesics do not induce ESRD and that the notion of "analgesic nephropathy" needs to be re-evaluated. PMID:18053232

Differential effects of common variants in SCN2A on general cognitive ability, brain physiology, and messenger RNA expression in schizophrenia cases and control individuals.

PubMed

Dickinson, Dwight; Straub, Richard E; Trampush, Joey W; Gao, Yuan; Feng, Ningping; Xie, Bin; Shin, Joo Heon; Lim, Hun Ki; Ursini, Gianluca; Bigos, Kristin L; Kolachana, Bhaskar; Hashimoto, Ryota; Takeda, Masatoshi; Baum, Graham L; Rujescu, Dan; Callicott, Joseph H; Hyde, Thomas M; Berman, Karen F; Kleinman, Joel E; Weinberger, Daniel R

2014-06-01

One approach to understanding the genetic complexity of schizophrenia is to study associated behavioral and biological phenotypes that may be more directly linked to genetic variation. To identify single-nucleotide polymorphisms associated with general cognitive ability (g) in people with schizophrenia and control individuals. Genomewide association study, followed by analyses in unaffected siblings and independent schizophrenia samples, functional magnetic resonance imaging studies of brain physiology in vivo, and RNA sequencing in postmortem brain samples. The discovery cohort and unaffected siblings were participants in the National Institute of Mental Health Clinical Brain Disorders Branch schizophrenia genetics studies. Additional schizophrenia cohorts were from psychiatric treatment settings in the United States, Japan, and Germany. The discovery cohort comprised 339 with schizophrenia and 363 community control participants. Follow-up analyses studied 147 unaffected siblings of the schizophrenia cases and independent schizophrenia samples including a total of an additional 668 participants. Imaging analyses included 87 schizophrenia cases and 397 control individuals. Brain tissue samples were available for 64 cases and 61 control individuals. We studied genomewide association with g, by group, in the discovery cohort. We used selected genotypes to test specific associations in unaffected siblings and independent schizophrenia samples. Imaging analyses focused on activation in the prefrontal cortex during working memory. Brain tissue studies yielded messenger RNA expression levels for RefSeq transcripts. The schizophrenia discovery cohort showed genomewide-significant association of g with polymorphisms in sodium channel gene SCN2A, accounting for 10.4% of g variance (rs10174400, P = 9.27 × 10(-10)). Control individuals showed a trend for g/genotype association with reversed allelic directionality. The genotype-by-group interaction was also genomewide significant (P = 1.75 × 10(-9)). Siblings showed a genotype association with g parallel to the schizophrenia group and the same interaction pattern. Parallel, but weaker, associations with cognition were found in independent schizophrenia samples. Imaging analyses showed a similar pattern of genotype associations by group and genotype-by-group interaction. Sequencing of RNA in brain revealed reduced expression in 2 of 3 SCN2A alternative transcripts in the patient group, with genotype-by-group interaction, that again paralleled the cognition effects. The findings implicate SCN2A and sodium channel biology in cognitive impairment in schizophrenia cases and unaffected relatives and may facilitate development of cognition-enhancing treatments.

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.

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.

Genome-wide Association Study of Obsessive-Compulsive Disorder

PubMed Central

Stewart, S Evelyn; Yu, Dongmei; Scharf, Jeremiah M; Neale, Benjamin M; Fagerness, Jesen A; Mathews, Carol A; Arnold, Paul D; Evans, Patrick D; Gamazon, Eric R; Osiecki, Lisa; McGrath, Lauren; Haddad, Stephen; Crane, Jacquelyn; Hezel, Dianne; Illman, Cornelia; Mayerfeld, Catherine; Konkashbaev, Anuar; Liu, Chunyu; Pluzhnikov, Anna; Tikhomirov, Anna; Edlund, Christopher K; Rauch, Scott L; Moessner, Rainald; Falkai, Peter; Maier, Wolfgang; Ruhrmann, Stephan; Grabe, Hans-Jörgen; Lennertz, Leonard; Wagner, Michael; Bellodi, Laura; Cavallini, Maria Cristina; Richter, Margaret A; Cook, Edwin H; Kennedy, James L; Rosenberg, David; Stein, Dan J; Hemmings, Sian MJ; Lochner, Christine; Azzam, Amin; Chavira, Denise A; Fournier, Eduardo; Garrido, Helena; Sheppard, Brooke; Umaña, Paul; Murphy, Dennis L; Wendland, Jens R; Veenstra-VanderWeele, Jeremy; Denys, Damiaan; Blom, Rianne; Deforce, Dieter; Van Nieuwerburgh, Filip; Westenberg, Herman GM; Walitza, Susanne; Egberts, Karin; Renner, Tobias; Miguel, Euripedes Constantino; Cappi, Carolina; Hounie, Ana G; Conceição do Rosário, Maria; Sampaio, Aline S; Vallada, Homero; Nicolini, Humberto; Lanzagorta, Nuria; Camarena, Beatriz; Delorme, Richard; Leboyer, Marion; Pato, Carlos N; Pato, Michele T; Voyiaziakis, Emanuel; Heutink, Peter; Cath, Danielle C; Posthuma, Danielle; Smit, Jan H; Samuels, Jack; Bienvenu, O Joseph; Cullen, Bernadette; Fyer, Abby J; Grados, Marco A; Greenberg, Benjamin D; McCracken, James T; Riddle, Mark A; Wang, Ying; Coric, Vladimir; Leckman, James F; Bloch, Michael; Pittenger, Christopher; Eapen, Valsamma; Black, Donald W; Ophoff, Roel A; Strengman, Eric; Cusi, Daniele; Turiel, Maurizio; Frau, Francesca; Macciardi, Fabio; Gibbs, J Raphael; Cookson, Mark R; Singleton, Andrew; Hardy, John; Crenshaw, Andrew T; Parkin, Melissa A; Mirel, Daniel B; Conti, David V; Purcell, Shaun; Nestadt, Gerald; Hanna, Gregory L; Jenike, Michael A; Knowles, James A; Cox, Nancy; Pauls, David L

2014-01-01

Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1,465 cases, 5,557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9,657 X-chromosome SNPs. Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two p-values were located within DLGAP1 (p=2.49×10-6 and p=3.44×10-6), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a p-value=3.84 × 10-8. However, when trios were meta-analyzed with the combined case-control samples, the p-value for this variant was 3.62×10-5, losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation-QTLs (p<0.001) and frontal lobe eQTLs (p=0.001) was observed within the top-ranked SNPs (p<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD. PMID:22889921

Plantar pressures are higher in cases with diabetic foot ulcers compared to controls despite a longer stance phase duration.

PubMed

Fernando, Malindu E; Crowther, Robert G; Lazzarini, Peter A; Sangla, Kunwarjit S; Wearing, Scott; Buttner, Petra; Golledge, Jonathan

2016-09-15

Current international guidelines advocate achieving at least a 30 % reduction in maximum plantar pressure to reduce the risk of foot ulcers in people with diabetes. However, whether plantar pressures differ in cases with foot ulcers to controls without ulcers is not clear. The aim of this study was to assess if plantar pressures were higher in patients with active plantar diabetic foot ulcers (cases) compared to patients with diabetes without a foot ulcer history (diabetes controls) and people without diabetes or a foot ulcer history (healthy controls). Twenty-one cases with diabetic foot ulcers, 69 diabetes controls and 56 healthy controls were recruited for this case-control study. Plantar pressures at ten sites on both feet and stance phase duration were measured using a pre-established protocol. Primary outcomes were mean peak plantar pressure, pressure-time integral and stance phase duration. Non-parametric analyses were used with Holm's correction to correct for multiple testing. Binary logistic regression models were used to adjust outcomes for age, sex and body mass index. Median differences with 95 % confidence intervals and Cohen's d values (standardised mean difference) were reported for all significant outcomes. The majority of ulcers were located on the plantar surface of the hallux and toes. When adjusted for age, sex and body mass index, the mean peak plantar pressure and pressure-time integral of toes and the mid-foot were significantly higher in cases compared to diabetes and healthy controls (p < 0.05). The stance phase duration was also significantly higher in cases compared to both control groups (p < 0.05). The main limitations of the study were the small number of cases studied and the inability to adjust analyses for multiple factors. This study shows that plantar pressures are higher in cases with active diabetic foot ulcers despite having a longer stance phase duration which would be expected to lower plantar pressure. Whether plantar pressure changes can predict ulcer healing should be the focus of future research. These results highlight the importance of offloading feet during active ulceration in addition to before ulceration.

Impact of Contextual Factors on Prostate Cancer Risk and Outcomes

DTIC Science & Technology

2013-07-01

framework with random effects (“frailty models”) while the case-control analyses (Aim 4) will use multilevel unconditional logistic regression models...contextual-level SES on prostate cancer risk within racial/ethnic groups. The survival analyses (Aims 1-3) will utilize a proportional hazards regression

Meta-analyses of the 5-HTTLPR polymorphisms and post-traumatic stress disorder.

PubMed

Navarro-Mateu, Fernando; Escámez, Teresa; Koenen, Karestan C; Alonso, Jordi; Sánchez-Meca, Julio

2013-01-01

To conduct a meta-analysis of all published genetic association studies of 5-HTTLPR polymorphisms performed in PTSD cases. Potential studies were identified through PubMed/MEDLINE, EMBASE, Web of Science databases (Web of Knowledge, WoK), PsychINFO, PsychArticles and HuGeNet (Human Genome Epidemiology Network) up until December 2011. Published observational studies reporting genotype or allele frequencies of this genetic factor in PTSD cases and in non-PTSD controls were all considered eligible for inclusion in this systematic review. Two reviewers selected studies for possible inclusion and extracted data independently following a standardized protocol. A biallelic and a triallelic meta-analysis, including the total S and S' frequencies, the dominant (S+/LL and S'+/L'L') and the recessive model (SS/L+ and S'S'/L'+), was performed with a random-effect model to calculate the pooled OR and its corresponding 95% CI. Forest plots and Cochran's Q-Statistic and I(2) index were calculated to check for heterogeneity. Subgroup analyses and meta-regression were carried out to analyze potential moderators. Publication bias and quality of reporting were also analyzed. 13 studies met our inclusion criteria, providing a total sample of 1874 patients with PTSD and 7785 controls in the biallelic meta-analyses and 627 and 3524, respectively, in the triallelic. None of the meta-analyses showed evidence of an association between 5-HTTLPR and PTSD but several characteristics (exposure to the same principal stressor for PTSD cases and controls, adjustment for potential confounding variables, blind assessment, study design, type of PTSD, ethnic distribution and Total Quality Score) influenced the results in subgroup analyses and meta-regression. There was no evidence of potential publication bias. Current evidence does not support a direct effect of 5-HTTLPR polymorphisms on PTSD. Further analyses of gene-environment interactions, epigenetic modulation and new studies with large samples and/or meta-analyses are required.

Biological Basis for Chemoprevention of Ovarian Cancer

DTIC Science & Technology

2003-10-01

birth control pill use are strongly protective. To achieve a better understanding of the etiology of ovarian cancer, which can then be translated into effective prevention strategies, we have initiated a case-control study that considers genetic susceptibility, epidemiologic risk factors and acquired genetic alterations. Subjects are interviewed in their homes and about 650 cases and 650 controls have been accrued thus far. Blood and cancer samples have been collected and molecular analyses of genetic polymorphisms (BRCA1/2, progesterone receptor) have been performed. An

Biological Basis for Chemoprevention of Ovarian Cancer

DTIC Science & Technology

2004-10-01

birth control pill use are strongly protective. To achieve a better understanding of the etiology of ovarian cancer, which can then be translated into effective prevention strategies, we have initiated a case-control study that considers genetic susceptibility, epidemiologic risk factors and acquired genetic alterations. Subjects are interviewed in their homes and about 750 cases and 750 controls have been accrued thus far. Blood and cancer samples have been collected and molecular analyses of genetic polymorphisms (BRCA1/2, progesterone receptor, vitamin D receptor,

Acute myeloid and chronic lymphoid leukaemias and exposure to low-level benzene among petroleum workers

PubMed Central

Rushton, L; Schnatter, A R; Tang, G; Glass, D C

2014-01-01

Background: High benzene exposure causes acute myeloid leukaemia (AML). Three petroleum case–control studies identified 60 cases (241 matched controls) for AML and 80 cases (345 matched controls) for chronic lymphoid leukaemia (CLL). Methods: Cases were classified and scored regarding uncertainty by two haematologists using available diagnostic information. Blinded quantitative benzene exposure assessment used work histories and exposure measurements adjusted for era-specific circumstances. Statistical analyses included conditional logistic regression and penalised smoothing splines. Results: Benzene exposures were much lower than previous studies. Categorical analyses showed increased ORs for AML with several exposure metrics, although patterns were unclear; neither continuous exposure metrics nor spline analyses gave increased risks. ORs were highest in terminal workers, particularly for Tanker Drivers. No relationship was found between benzene exposure and risk of CLL, although the Australian study showed increased risks in refinery workers. Conclusion: Overall, this study does not persuasively demonstrate a risk between benzene and AML. A previously reported strong relationship between myelodysplastic syndrome (MDS) (potentially previously reported as AML) at our study's low benzene levels suggests that MDS may be the more relevant health risk for lower exposure. Higher CLL risks in refinery workers may be due to more diverse exposures than benzene alone. PMID:24357793

A genome-wide association study of anorexia nervosa.

PubMed

Boraska, V; Franklin, C S; Floyd, J A B; Thornton, L M; Huckins, L M; Southam, L; Rayner, N W; Tachmazidou, I; Klump, K L; Treasure, J; Lewis, C M; Schmidt, U; Tozzi, F; Kiezebrink, K; Hebebrand, J; Gorwood, P; Adan, R A H; Kas, M J H; Favaro, A; Santonastaso, P; Fernández-Aranda, F; Gratacos, M; Rybakowski, F; Dmitrzak-Weglarz, M; Kaprio, J; Keski-Rahkonen, A; Raevuori, A; Van Furth, E F; Slof-Op 't Landt, M C T; Hudson, J I; Reichborn-Kjennerud, T; Knudsen, G P S; Monteleone, P; Kaplan, A S; Karwautz, A; Hakonarson, H; Berrettini, W H; Guo, Y; Li, D; Schork, N J; Komaki, G; Ando, T; Inoko, H; Esko, T; Fischer, K; Männik, K; Metspalu, A; Baker, J H; Cone, R D; Dackor, J; DeSocio, J E; Hilliard, C E; O'Toole, J K; Pantel, J; Szatkiewicz, J P; Taico, C; Zerwas, S; Trace, S E; Davis, O S P; Helder, S; Bühren, K; Burghardt, R; de Zwaan, M; Egberts, K; Ehrlich, S; Herpertz-Dahlmann, B; Herzog, W; Imgart, H; Scherag, A; Scherag, S; Zipfel, S; Boni, C; Ramoz, N; Versini, A; Brandys, M K; Danner, U N; de Kovel, C; Hendriks, J; Koeleman, B P C; Ophoff, R A; Strengman, E; van Elburg, A A; Bruson, A; Clementi, M; Degortes, D; Forzan, M; Tenconi, E; Docampo, E; Escaramís, G; Jiménez-Murcia, S; Lissowska, J; Rajewski, A; Szeszenia-Dabrowska, N; Slopien, A; Hauser, J; Karhunen, L; Meulenbelt, I; Slagboom, P E; Tortorella, A; Maj, M; Dedoussis, G; Dikeos, D; Gonidakis, F; Tziouvas, K; Tsitsika, A; Papezova, H; Slachtova, L; Martaskova, D; Kennedy, J L; Levitan, R D; Yilmaz, Z; Huemer, J; Koubek, D; Merl, E; Wagner, G; Lichtenstein, P; Breen, G; Cohen-Woods, S; Farmer, A; McGuffin, P; Cichon, S; Giegling, I; Herms, S; Rujescu, D; Schreiber, S; Wichmann, H-E; Dina, C; Sladek, R; Gambaro, G; Soranzo, N; Julia, A; Marsal, S; Rabionet, R; Gaborieau, V; Dick, D M; Palotie, A; Ripatti, S; Widén, E; Andreassen, O A; Espeseth, T; Lundervold, A; Reinvang, I; Steen, V M; Le Hellard, S; Mattingsdal, M; Ntalla, I; Bencko, V; Foretova, L; Janout, V; Navratilova, M; Gallinger, S; Pinto, D; Scherer, S W; Aschauer, H; Carlberg, L; Schosser, A; Alfredsson, L; Ding, B; Klareskog, L; Padyukov, L; Courtet, P; Guillaume, S; Jaussent, I; Finan, C; Kalsi, G; Roberts, M; Logan, D W; Peltonen, L; Ritchie, G R S; Barrett, J C; Estivill, X; Hinney, A; Sullivan, P F; Collier, D A; Zeggini, E; Bulik, C M

2014-10-01

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

A genome-wide association study of anorexia nervosa

PubMed Central

Boraska, Vesna; Franklin, Christopher S; Floyd, James AB; Thornton, Laura M; Huckins, Laura M; Southam, Lorraine; Rayner, N William; Tachmazidou, Ioanna; Klump, Kelly L; Treasure, Janet; Lewis, Cathryn M; Schmidt, Ulrike; Tozzi, Federica; Kiezebrink, Kirsty; Hebebrand, Johannes; Gorwood, Philip; Adan, Roger AH; Kas, Martien JH; Favaro, Angela; Santonastaso, Paolo; Fernández-Aranda, Fernando; Gratacos, Monica; Rybakowski, Filip; Dmitrzak-Weglarz, Monika; Kaprio, Jaakko; Keski-Rahkonen, Anna; Raevuori, Anu; Van Furth, Eric F; Landt, Margarita CT Slof-Op t; Hudson, James I; Reichborn-Kjennerud, Ted; Knudsen, Gun Peggy S; Monteleone, Palmiero; Kaplan, Allan S; Karwautz, Andreas; Hakonarson, Hakon; Berrettini, Wade H; Guo, Yiran; Li, Dong; Schork, Nicholas J.; Komaki, Gen; Ando, Tetsuya; Inoko, Hidetoshi; Esko, Tõnu; Fischer, Krista; Männik, Katrin; Metspalu, Andres; Baker, Jessica H; Cone, Roger D; Dackor, Jennifer; DeSocio, Janiece E; Hilliard, Christopher E; O'Toole, Julie K; Pantel, Jacques; Szatkiewicz, Jin P; Taico, Chrysecolla; Zerwas, Stephanie; Trace, Sara E; Davis, Oliver SP; Helder, Sietske; Bühren, Katharina; Burghardt, Roland; de Zwaan, Martina; Egberts, Karin; Ehrlich, Stefan; Herpertz-Dahlmann, Beate; Herzog, Wolfgang; Imgart, Hartmut; Scherag, André; Scherag, Susann; Zipfel, Stephan; Boni, Claudette; Ramoz, Nicolas; Versini, Audrey; Brandys, Marek K; Danner, Unna N; de Kovel, Carolien; Hendriks, Judith; Koeleman, Bobby PC; Ophoff, Roel A; Strengman, Eric; van Elburg, Annemarie A; Bruson, Alice; Clementi, Maurizio; Degortes, Daniela; Forzan, Monica; Tenconi, Elena; Docampo, Elisa; Escaramís, Geòrgia; Jiménez-Murcia, Susana; Lissowska, Jolanta; Rajewski, Andrzej; Szeszenia-Dabrowska, Neonila; Slopien, Agnieszka; Hauser, Joanna; Karhunen, Leila; Meulenbelt, Ingrid; Slagboom, P Eline; Tortorella, Alfonso; Maj, Mario; Dedoussis, George; Dikeos, Dimitris; Gonidakis, Fragiskos; Tziouvas, Konstantinos; Tsitsika, Artemis; Papezova, Hana; Slachtova, Lenka; Martaskova, Debora; Kennedy, James L.; Levitan, Robert D.; Yilmaz, Zeynep; Huemer, Julia; Koubek, Doris; Merl, Elisabeth; Wagner, Gudrun; Lichtenstein, Paul; Breen, Gerome; Cohen-Woods, Sarah; Farmer, Anne; McGuffin, Peter; Cichon, Sven; Giegling, Ina; Herms, Stefan; Rujescu, Dan; Schreiber, Stefan; Wichmann, H-Erich; Dina, Christian; Sladek, Rob; Gambaro, Giovanni; Soranzo, Nicole; Julia, Antonio; Marsal, Sara; Rabionet, Raquel; Gaborieau, Valerie; Dick, Danielle M; Palotie, Aarno; Ripatti, Samuli; Widén, Elisabeth; Andreassen, Ole A; Espeseth, Thomas; Lundervold, Astri; Reinvang, Ivar; Steen, Vidar M; Le Hellard, Stephanie; Mattingsdal, Morten; Ntalla, Ioanna; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Navratilova, Marie; Gallinger, Steven; Pinto, Dalila; Scherer, Stephen; Aschauer, Harald; Carlberg, Laura; Schosser, Alexandra; Alfredsson, Lars; Ding, Bo; Klareskog, Lars; Padyukov, Leonid; Finan, Chris; Kalsi, Gursharan; Roberts, Marion; Logan, Darren W; Peltonen, Leena; Ritchie, Graham RS; Barrett, Jeffrey C; Estivill, Xavier; Hinney, Anke; Sullivan, Patrick F; Collier, David A; Zeggini, Eleftheria; Bulik, Cynthia M

2015-01-01

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2,907 cases with AN from 14 countries (15 sites) and 14,860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery datasets. Seventy-six (72 independent) SNPs were taken forward for in silico (two datasets) or de novo (13 datasets) replication genotyping in 2,677 independent AN cases and 8,629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication datasets comprised 5,551 AN cases and 21,080 controls. AN subtype analyses (1,606 AN restricting; 1,445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01×10-7) in SOX2OT and rs17030795 (P=5.84×10-6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76×10-6) between CUL3 and FAM124B and rs1886797 (P=8.05×10-6) near SPATA13. Comparing discovery to replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4×10-6), strongly suggesting that true findings exist but that our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field. PMID:24514567

Waist circumference and waist-to-hip ratio in carpal tunnel syndrome: a case-control study.

PubMed

Mondelli, Mauro; Aretini, Alessandro; Ginanneschi, Federica; Greco, Giuseppe; Mattioli, Stefano

2014-03-15

The association between carpal tunnel syndrome (CTS) and high body mass index (BMI) and some hand measures is well known. No study has been specifically focused on waist circumference (WC) and waist-to-hip-ratio (WHR). The aim of this prospective case-control study is to evaluate the association between CTS and WC, WHR and other body and hand anthropometric measures. We consecutively enrolled one "idiopathic" CTS case for two controls in 3 outpatient electromyography labs. The main anthropometric measures were BMI, WC, WHR, wrist ratio (WR) and hand ratio (HR). We performed univariate and multivariate analyses. Female cases and controls were 250 and 474 and male cases and controls were 120 and 273, respectively. At univariate analysis there were differences in many anthropometric measures between cases and controls. At multivariate logistic regression analyses high BMI, WC and WHR and abnormal HR and WR were independent risk factors for CTS. Crossing two categories between BMI, WC and WHR, the overweight subjects, especially females, were at risk only if they had very high WC or high WHR. The risk increased if they were obese. High WC/WHR doubles the risk of CTS, the risk further increased if overweight/obese subjects have also very high WC or high WHR. The obese subjects were always at risk regardless of WC and WHR values. Metabolic causes of this association with CTS were hypothesised. BMI is not the only and most powerful body predictor of "idiopathic" CTS, but also WHR and WC should be considered. These measures may not be interchangeable and it may be desirable to consider the utility of their joint use. Copyright © 2014 Elsevier B.V. All rights reserved.

How a "Top-Performing" Asian School System Formulates and Implements Policy: The Case of Singapore

ERIC Educational Resources Information Center

Tan, Cheng Yong; Dimmock, Clive

2014-01-01

This article analyses the paradox inherent in the "top-performing" yet tightly controlled Singapore education system. As government controls have increased in complexity, existing policymaking conceptual heuristics in accounting for centre-periphery relationships appear inadequate. It argues that more direct government control is being…

Delivery strategies to optimize resource utilization and performance status for patients with advanced life-limiting illness: results from the "palliative care trial" [ISRCTN 81117481].

PubMed

Abernethy, Amy P; Currow, David C; Shelby-James, Tania; Rowett, Debra; May, Frank; Samsa, Gregory P; Hunt, Roger; Williams, Helena; Esterman, Adrian; Phillips, Paddy A

2013-03-01

Evidence-based approaches are needed to improve the delivery of specialized palliative care. The aim of this trial was to improve on current models of service provision. This 2×2×2 factorial cluster randomized controlled trial was conducted at an Australian community-based palliative care service, allowing three simultaneous comparative effectiveness studies. Participating patients were newly referred adults, experiencing pain, and who were expected to live >48 hours. Patients enrolled with their general practitioners (GPs) and were randomized three times: 1) individualized interdisciplinary case conference including their GP vs. control, 2) educational outreach visiting for GPs about pain management vs. control, and 3) structured educational visiting for patients/caregivers about pain management vs. control. The control condition was current palliative care. Outcomes included Australia-modified Karnofsky Performance Status (AKPS) and pain from 60 days after randomization and hospitalizations. There were 461 participants: mean age 71 years, 50% male, 91% with cancer, median survival 179 days, and median baseline AKPS 60. Only 47% of individuals randomized to the case conferencing intervention received it; based on a priori-defined analyses, 32% of participants were included in final analyses. Case conferencing reduced hospitalizations by 26% (least squares means hospitalizations per patient: case conference 1.26 [SE 0.10] vs. control 1.70 [SE 0.13], P=0.0069) and better maintained performance status (AKPS case conferences 57.3 [SE 1.5] vs. control 51.7 [SE 2.3], P=0.0368). Among patients with declining function (AKPS <70), case conferencing and patient/caregiver education better maintained performance status (AKPS case conferences 55.0 [SE 2.1] vs. control 46.5 [SE 2.9], P=0.0143; patient/caregiver education 54.7 [SE 2.8] vs. control 46.8 [SE 2.1], P=0.0206). Pain was unchanged. GP education did not change outcomes. A single case conference added to current specialized community-based palliative care reduced hospitalizations and better maintained performance status. Comparatively, patient/caregiver education was less effective; GP education was not effective. Copyright © 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Risk of acute liver injury associated with use of antibiotics. Comparative cohort and nested case-control studies using two primary care databases in Europe.

PubMed

Brauer, Ruth; Douglas, Ian; Garcia Rodriguez, Luis Alberto; Downey, Gerald; Huerta, Consuelo; de Abajo, Francisco; Bate, Andrew; Feudjo Tepie, Maurille; de Groot, Mark C H; Schlienger, Raymond; Reynolds, Robert; Smeeth, Liam; Klungel, Olaf; Ruigómez, Ana

2016-03-01

To assess the impact of varying study designs, exposure and outcome definitions on the risk of acute liver injury (ALI) associated with antibiotic use. The source population comprised of patients registered in two primary care databases, in the UK and in Spain. We identified a cohort consisting of new users of antibiotics during the study period (2004-2009) and non-users during the study period or in the previous year. Cases with ALI were identified within this cohort and classified as definite or probable, based on recorded medical information. The relative risk (RR) of ALI associated with antibiotic use was computed using Poisson regression. For the nested case-control analyses, up to five controls were matched to each case by age, sex, date and practice (in CPRD) and odds ratios (OR) were computed with conditional logistic regression. The age, sex and year adjusted RRs of definite ALI in the current antibiotic use periods was 10.04 (95% CI: 6.97-14.47) in CPRD and 5.76 (95% CI: 3.46-9.59) in BIFAP. In the case-control analyses adjusting for life-style, comorbidities and use of medications, the OR of ALI for current users of antibiotics was and 5.7 (95% CI: 3.46-9.36) in CPRD and 2.6 (95% CI: 1.26-5.37) in BIFAP. Guided by a common protocol, both cohort and case-control study designs found an increased risk of ALI associated with the use of antibiotics in both databases, independent of the exposure and case definitions used. However, the magnitude of the risk was higher in CPRD compared to BIFAP. Copyright © 2016 John Wiley & Sons, Ltd.

Psychosocial factors in childhood pedestrian injury: a matched case-control study. Kid's'n'Cars Team.

PubMed

Christoffel, K K; Donovan, M; Schofer, J; Wills, K; Lavigne, J V

1996-01-01

Psychosocial factors--such as hyperactivity and low family cohesion--contribute to the risk for child pedestrian injury (PI), even after controlling for known demographic risk factors. Urban PI victims aged 5 to 12 years were recruited from one large, urban pediatric trauma center in a large city. One hundred twenty-eight cases were matched to uninjured children on age, sex, race, location of residence, and parental education. Among matched cases: 70% were male, 41% were black, 33% were Hispanic, and 66% of the mothers had a high school education or less. RESEARCH DESIGN AND MEASUREMENTS: Case-control comparisons on 19 psychosocial variables drawn from interviews and standardized tests, using one-tailed matched-pairs t tests and conditional logistic regression analyses. Cases had higher reported physical quotient [PQ] (P = .01), self-help quotient (P = .04), and family stress (P = .02), and lower family supportiveness (P = .03). Multivariate analyses confirmed that PQ was higher in cases (10-point increase: odds ratio (OR) = 1.32 [90% confidence interval (CI) 1.01-1.76], that stress was higher in cases (1 log increase: OR 2.13, [1.26-3.61]), and that cases had lower family supportiveness (25-point decrease: OR 1.43 [1.25-1.63]). It also identified household crowding as a factor for non-black cases (OR for increase of 0.25 people per room: 2.18, [1.31-3.62]). Even when controlling for demographic risk, several family factors and one child factor place children at risk for PI. Clinicians may choose to use these as indicators for injury prevention counseling. Research on family effects may help clarify means to protect children who are demographically at risk for PI.

Quality Assessment of Studies Published in Open Access and Subscription Journals: Results of a Systematic Evaluation.

PubMed

Pastorino, Roberta; Milovanovic, Sonja; Stojanovic, Jovana; Efremov, Ljupcho; Amore, Rosarita; Boccia, Stefania

2016-01-01

Along with the proliferation of Open Access (OA) publishing, the interest for comparing the scientific quality of studies published in OA journals versus subscription journals has also increased. With our study we aimed to compare the methodological quality and the quality of reporting of primary epidemiological studies and systematic reviews and meta-analyses published in OA and non-OA journals. In order to identify the studies to appraise, we listed all OA and non-OA journals which published in 2013 at least one primary epidemiologic study (case-control or cohort study design), and at least one systematic review or meta-analysis in the field of oncology. For the appraisal, we picked up the first studies published in 2013 with case-control or cohort study design from OA journals (Group A; n = 12), and in the same time period from non-OA journals (Group B; n = 26); the first systematic reviews and meta-analyses published in 2013 from OA journals (Group C; n = 15), and in the same time period from non-OA journals (Group D; n = 32). We evaluated the methodological quality of studies by assessing the compliance of case-control and cohort studies to Newcastle and Ottawa Scale (NOS) scale, and the compliance of systematic reviews and meta-analyses to Assessment of Multiple Systematic Reviews (AMSTAR) scale. The quality of reporting was assessed considering the adherence of case-control and cohort studies to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist, and the adherence of systematic reviews and meta-analyses to Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) checklist. Among case-control and cohort studies published in OA and non-OA journals, we did not observe significant differences in the median value of NOS score (Group A: 7 (IQR 7-8) versus Group B: 8 (7-9); p = 0.5) and in the adherence to STROBE checklist (Group A, 75% versus Group B, 80%; p = 0.1). The results did not change after adjustment for impact factor. The compliance with AMSTAR and adherence to PRISMA checklist were comparable between systematic reviews and meta-analyses published in OA and non-OA journals (Group C, 46.0% versus Group D, 55.0%; p = 0.06), (Group C, 72.0% versus Group D, 76.0%; p = 0.1), respectively). The epidemiological studies published in OA journals in the field of oncology approach the same methodological quality and quality of reporting as studies published in non-OA journals.

Quality Assessment of Studies Published in Open Access and Subscription Journals: Results of a Systematic Evaluation

PubMed Central

Pastorino, Roberta; Milovanovic, Sonja; Stojanovic, Jovana; Efremov, Ljupcho; Amore, Rosarita; Boccia, Stefania

2016-01-01

Introduction Along with the proliferation of Open Access (OA) publishing, the interest for comparing the scientific quality of studies published in OA journals versus subscription journals has also increased. With our study we aimed to compare the methodological quality and the quality of reporting of primary epidemiological studies and systematic reviews and meta-analyses published in OA and non-OA journals. Methods In order to identify the studies to appraise, we listed all OA and non-OA journals which published in 2013 at least one primary epidemiologic study (case-control or cohort study design), and at least one systematic review or meta-analysis in the field of oncology. For the appraisal, we picked up the first studies published in 2013 with case-control or cohort study design from OA journals (Group A; n = 12), and in the same time period from non-OA journals (Group B; n = 26); the first systematic reviews and meta-analyses published in 2013 from OA journals (Group C; n = 15), and in the same time period from non-OA journals (Group D; n = 32). We evaluated the methodological quality of studies by assessing the compliance of case-control and cohort studies to Newcastle and Ottawa Scale (NOS) scale, and the compliance of systematic reviews and meta-analyses to Assessment of Multiple Systematic Reviews (AMSTAR) scale. The quality of reporting was assessed considering the adherence of case-control and cohort studies to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist, and the adherence of systematic reviews and meta-analyses to Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) checklist. Results Among case-control and cohort studies published in OA and non-OA journals, we did not observe significant differences in the median value of NOS score (Group A: 7 (IQR 7–8) versus Group B: 8 (7–9); p = 0.5) and in the adherence to STROBE checklist (Group A, 75% versus Group B, 80%; p = 0.1). The results did not change after adjustment for impact factor. The compliance with AMSTAR and adherence to PRISMA checklist were comparable between systematic reviews and meta-analyses published in OA and non-OA journals (Group C, 46.0% versus Group D, 55.0%; p = 0.06), (Group C, 72.0% versus Group D, 76.0%; p = 0.1), respectively). Conclusion The epidemiological studies published in OA journals in the field of oncology approach the same methodological quality and quality of reporting as studies published in non-OA journals. PMID:27167982

Ultrasound analysis of mental artery flow in elderly patients: a case–control study

PubMed Central

Baladi, Marina G; Tucunduva Neto, Raul R C M; Aoki, Eduardo M; Arita, Emiko S; Freitas, Claudio F

2015-01-01

Objectives: Mental artery flow decreases with age and may have an aetiological role in alveolar ridge atrophy. The aim of this study was to identify factors associated with alterations of mental artery flow, assessed by ultrasonography. Methods: This case–control study was conducted on elderly patients (aged above 60 years) at the beginning of dental treatment. Intraoral B-mode Doppler ultrasonography was used to assess mental artery flow. The cases were defined as patients with a weak/absent ultrasound signal, whereas the controls presented a strong ultrasound signal. Demographics and radiographic findings (low bone mineral density on dual-energy X-ray absorptiometry and mandibular cortical index on panoramic radiographs) were analysed as risk factors for weak/absent ultrasound signal and were calculated as adjusted odds ratios (AORs) with 95% confidence intervals (CIs) using conditional logistic regression. In addition, the Student's t-test was used to compare the mean alveolar bone height of the analysed groups. A p-value <0.05 was considered statistically significant. Results: A total of 30 ultrasound examinations (12 cases and 18 controls) were analysed. A weak/absent mental artery pulse strength was significantly associated with edentulism (AOR = 3.67; 95% CI = 0.86–15.63; p = 0.046). In addition, there was a significant difference in alveolar bone height between edentulous cases and controls (p = 0.036). Conclusions: Within the limitations of this study, the present results indicate that edentulism is associated with diminished mental artery flow, which, in turn, affects alveolar bone height. PMID:26205777

Economics of infection control surveillance technology: cost-effective or just cost?

PubMed

Furuno, Jon P; Schweizer, Marin L; McGregor, Jessina C; Perencevich, Eli N

2008-04-01

Previous studies have suggested that informatics tools, such as automated alert and decision support systems, may increase the efficiency and quality of infection control surveillance. However, little is known about the cost-effectiveness of these tools. We focus on 2 types of economic analyses that have utility in assessing infection control interventions (cost-effectiveness analysis and business-case analysis) and review the available literature on the economics of computerized infection control surveillance systems. Previous studies on the effectiveness of computerized infection control surveillance have been limited to assessments of whether these tools increase the sensitivity and specificity of surveillance over traditional methods. Furthermore, we identified only 2 studies that assessed the costs associated with computerized infection control surveillance. Thus, it remains unknown whether computerized infection control surveillance systems are cost-effective and whether use of these systems improves patient outcomes. The existing data are insufficient to allow for a summary conclusion on the cost-effectiveness of infection control surveillance technology. All future studies of computerized infection control surveillance systems should aim to collect outcomes and economic data to inform decision making and assist hospitals with completing business-cases analyses.

Missing heritability in the tails of quantitative traits? A simulation study on the impact of slightly altered true genetic models.

PubMed

Pütter, Carolin; Pechlivanis, Sonali; Nöthen, Markus M; Jöckel, Karl-Heinz; Wichmann, Heinz-Erich; Scherag, André

2011-01-01

Genome-wide association studies have identified robust associations between single nucleotide polymorphisms and complex traits. As the proportion of phenotypic variance explained is still limited for most of the traits, larger and larger meta-analyses are being conducted to detect additional associations. Here we investigate the impact of the study design and the underlying assumption about the true genetic effect in a bimodal mixture situation on the power to detect associations. We performed simulations of quantitative phenotypes analysed by standard linear regression and dichotomized case-control data sets from the extremes of the quantitative trait analysed by standard logistic regression. Using linear regression, markers with an effect in the extremes of the traits were almost undetectable, whereas analysing extremes by case-control design had superior power even for much smaller sample sizes. Two real data examples are provided to support our theoretical findings and to explore our mixture and parameter assumption. Our findings support the idea to re-analyse the available meta-analysis data sets to detect new loci in the extremes. Moreover, our investigation offers an explanation for discrepant findings when analysing quantitative traits in the general population and in the extremes. Copyright © 2011 S. Karger AG, Basel.

Biomarkers and Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analyses

ERIC Educational Resources Information Center

Scassellati, Catia; Bonvicini, Cristian; Faraone, Stephen V.; Gennarelli, Massimo

2012-01-01

Objective: To determine whether peripheral biochemical markers (biomarkers) might differentiate patients with attention-deficit/hyperactivity disorder (ADHD) from non-ADHD individuals. Method: We conducted a systematic search and a series of meta-analyses of case-control studies comprising studies from 1969 to 2011. Results: We identified 210…

Consortium on the Genetics of Schizophrenia (COGS) assessment of endophenotypes for schizophrenia: an introduction to this Special Issue of Schizophrenia Research.

PubMed

Swerdlow, Neal R; Gur, Raquel E; Braff, David L

2015-04-01

The COGS is a multi-site NIMH-sponsored investigation of the genetic basis of 12 primary and multiple secondary quantitative endophenotypes in schizophrenia. Since 2003, COGS has completed studies using a family-based ascertainment strategy (COGS-1), and a case-control ascertainment strategy (COGS-2) (cumulative "n">4000). COGS-1 family study confirmed robust deficits in, and heritability of, these endophenotypes in schizophrenia, and provided evidence for a coherent genetic architecture underlying the risk for neurocognitive and neurophysiological deficits in this disorder. COGS-2 case-control findings, many reported herein, establish a foundation for fine genomic mapping and other analyses of these endophenotypes and risk genes for SZ. Several reports in this Special Issue compare findings of endophenotype deficits generated by fundamentally different COGS-1 vs. COGS-2 ascertainment strategies. Despite the expectation that family-based and case-control designs would establish demographically and potentially biologically distinct patient cohorts, findings generally revealed comparable patterns of endophenotype deficits across studies. The COGS-2 case-control design facilitated the accrual of a larger "n", permitting detailed analyses of factors moderating endophenotype performance. Some COGS-2 endophenotypes not assessed in COGS-1 are also reported, as is a new factor analytic strategy for identifying shared vs. unique factors among the COGS endophenotypes which can be used to develop composite variables with distinct genetic signatures. The path to date of COGS-1 endophenotype and genetic findings, followed by replication and extension in COGS-2, establishes benchmarks for endophenotype deficits in SZ and their moderation by specific factors, and clear expectations for informative findings from upcoming COGS-2 genetic analyses. Published by Elsevier B.V.

Control performance of a road vehicle with four independent single-wheel electric motors and steer-by-wire system

NASA Astrophysics Data System (ADS)

Weiskircher, Thomas; Müller, Steffen

2012-01-01

This article presents a motion controller for a road vehicle equipped with a steer-by-wire system and four independent electric rim-mounted drives. The motion controller separates the control law from the specific actuator setup by the usage of virtual global control variables acting on the vehicle centre of gravity. A control allocation algorithm distributes the virtual control variables to the available actuators. An approximation of the real actuator dynamics is used to analyse the performance of different motion controller types in the linear and nonlinear driving regions. In addition, a vehicle state observer consisting of a traction force observer and an unscented Kalman filter is discussed to analyse the control behaviour in the case of a real sensor setup.

The Multiple Control of Verbal Behavior

PubMed Central

Michael, Jack; Palmer, David C; Sundberg, Mark L

2011-01-01

Amid the novel terms and original analyses in Skinner's Verbal Behavior, the importance of his discussion of multiple control is easily missed, but multiple control of verbal responses is the rule rather than the exception. In this paper we summarize and illustrate Skinner's analysis of multiple control and introduce the terms convergent multiple control and divergent multiple control. We point out some implications for applied work and discuss examples of the role of multiple control in humor, poetry, problem solving, and recall. Joint control and conditional discrimination are discussed as special cases of multiple control. We suggest that multiple control is a useful analytic tool for interpreting virtually all complex behavior, and we consider the concepts of derived relations and naming as cases in point. PMID:22532752

Keeping children safe at home: protocol for three matched case–control studies of modifiable risk factors for falls

PubMed Central

Kendrick, Denise; Stewart, Jane; Clacy, Rose; Coffey, Frank; Cooper, Nicola; Coupland, Carol; Hayes, Mike; McColl, Elaine; Reading, Richard; Sutton, Alex; M L Towner, Elizabeth; Craig Watson, Michael

2012-01-01

Background Childhood falls result in considerable morbidity, mortality and health service use. Despite this, little evidence exists on protective factors or effective falls prevention interventions in young children. Objectives To estimate ORs for three types of medically attended fall injuries in young children in relation to safety equipment, safety behaviours and hazard reduction and explore differential effects by child and family factors and injury severity. Design Three multicentre case–control studies in UK hospitals with validation of parental reported exposures using home observations. Cases are aged 0–4 years with a medically attended fall injury occurring at home, matched on age and sex with community controls. Children attending hospital for other types of injury will serve as unmatched hospital controls. Matched analyses will use conditional logistic regression to adjust for potential confounding variables. Unmatched analyses will use unconditional logistic regression, adjusted for age, sex, deprivation and distance from hospital in addition to other confounders. Each study requires 496 cases and 1984 controls to detect an OR of 0.7, with 80% power, 5% significance level, a correlation between cases and controls of 0.1 and a range of exposure prevalences. Main outcome measures Falls on stairs, on one level and from furniture. Discussion As the largest in the field to date, these case control studies will adjust for potential confounders, validate measures of exposure and investigate modifiable risk factors for specific falls injury mechanisms. Findings should enhance the evidence base for falls prevention for young children. PMID:22628151

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.

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.

Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis.

PubMed

Ivers, Louise C; Hilaire, Isabelle J; Teng, Jessica E; Almazor, Charles P; Jerome, J Gregory; Ternier, Ralph; Boncy, Jacques; Buteau, Josiane; Murray, Megan B; Harris, Jason B; Franke, Molly F

2015-03-01

Between April and June, 2012, a reactive cholera vaccination campaign was done in Haiti with an oral inactivated bivalent whole-cell vaccine. We aimed to assess the effectiveness of the vaccine in a case-control study and to assess the likelihood of bias in that study in a bias-indicator study. Residents of Bocozel or Grand Saline who were eligible for the vaccination campaign (ie, age ≥12 months, not pregnant, and living in the region at the time of the vaccine campaign) were included. In the primary case-control study, cases had acute watery diarrhoea, sought treatment at one of three participating cholera treatment units, and had a stool sample positive for cholera by culture. For each case, four control individuals who did not seek treatment for acute watery diarrhoea were matched by location of residence, enrolment time (within 2 weeks of the case), and age (1-4 years, 5-15 years, and >15 years). Cases in the bias-indicator study were individuals with acute watery diarrhoea with a negative stool sample for cholera. Controls were selected in the same manner as in the primary case-control study. Trained staff used standard laboratory procedures to do rapid tests and stool cultures from study cases. Participants were interviewed to collect data on sociodemographic characteristics, risk factors for cholera, and self-reported vaccination. Data were analysed by conditional logistic regression, adjusting for matching factors. From Oct 24, 2012, to March 9, 2014, 114 eligible individuals presented with acute watery diarrhoea and were enrolled, 25 of whom were subsequently excluded. 47 participants were analysed as cases in the vaccine effectiveness case-control study and 42 as cases in the bias-indicator study. 33 (70%) of 47 cholera cases self-reported vaccination versus 167 (89%) of 188 controls (vaccine effectiveness 63%, 95% CI 8-85). 27 (57%) of 47 cases had certified vaccination versus 147 (78%) of 188 controls (vaccine effectiveness 58%, 13-80). Neither self-reported nor verified vaccination was significantly associated with non-cholera diarrhoea (vaccine effectiveness 18%, 95% CI -208 to 78 by self-report and -21%, -238 to 57 by verified vaccination). Bivalent whole-cell oral cholera vaccine effectively protected against cholera in Haiti from 4 months to 24 months after vaccination. Vaccination is an important component of efforts to control cholera epidemics. National Institutes of Health, Delivering Oral Vaccines Effectively project, and Department of Global Health and Social Medicine at Harvard Medical School. Copyright © 2015 Ivers et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by .. All rights reserved.

Risk factors associated with asbestos-related diseases: a community-based case-control study.

PubMed

Rosell-Murphy, Magdalena-Isabel; Abós-Herràndiz, Rafael; Olivella, Josep Tarrés; Alberti-Casas, Constança; Allas, Isabel García; Artés, Xavier Martinez; Günther, Ilona Krier; Malet, Isidre Grimau; Martínez, Ramon Orriols; Canela-Soler, Jaume

2013-08-06

Asbestos is a first level carcinogen. However, few epidemiological studies analyse the risk and protective factors associated with asbestos-related diseases and follow up these conditions in the general population. Pleural mesothelioma, caused by inhalation of asbestos fibres at work, at home or in the environment, is the most representative asbestos-related disease.The objectives of this study are to analyse the risk and protective factors associated with asbestos-related diseases and to investigate the incidence of new clinical manifestations in patients already diagnosed with some form of ARD. We have designed a matched case-control study with follow up of both cohorts from a population of a health district of the Barcelona province that has been exposed to asbestos for a period of 90 years. A better understanding of asbestos-related diseases should improve i) the clinical and epidemiological follow up of patients with this condition; ii) the design of new treatment strategies; iii) and the development of preventive activities. At the end of the study, the two cohorts created in this study (affected cases and healthy controls) will constitute the basis for future research.

Association between environmental factors including second-hand smoke and primary lung cancer in dogs.

PubMed

Zierenberg-Ripoll, A; Pollard, R E; Stewart, S L; Allstadt, S D; Barrett, L E; Gillem, J M; Skorupski, K A

2018-06-01

To estimate prevalence of exposure to environmental tobacco smoke and other environmental toxins in dogs with primary lung tumours and to analyse association between exposure and lung tumour development. In this case-control study, an owner survey was developed to collect data on patient characteristics, general health care and environmental exposures. Dogs diagnosed with primary lung carcinomas formed the Case group. Dogs diagnosed with mast cell tumours served as Control Group 1 and dogs diagnosed with neurologic disease served as Control Group 2. Associations between diagnosis of primary lung tumour and patient and environmental exposure variables were analysed using bivariate and multivariate statistical methods. A total of 1178 owner surveys were mailed and 470 surveys were returned and included in statistical analysis, including 135 Cases, 169 dogs in Control Group 1 and 166 dogs in Control Group 2. An association between exposure to second-hand smoke and prevalence of primary lung cancer was not identified in this study. Second-hand smoke is associated with primary lung cancer in people but a definitive association has not been found in dogs. The results of this study suggest that tobacco smoke exposure may not be associated with primary lung cancer development in dogs but study limitations may have precluded detection of an association. © 2017 British Small Animal Veterinary Association.

Genetic overlap between diagnostic subtypes of ischemic stroke.

PubMed

Holliday, Elizabeth G; Traylor, Matthew; Malik, Rainer; Bevan, Steve; Falcone, Guido; Hopewell, Jemma C; Cheng, Yu-Ching; Cotlarciuc, Ioana; Bis, Joshua C; Boerwinkle, Eric; Boncoraglio, Giorgio B; Clarke, Robert; Cole, John W; Fornage, Myriam; Furie, Karen L; Ikram, M Arfan; Jannes, Jim; Kittner, Steven J; Lincz, Lisa F; Maguire, Jane M; Meschia, James F; Mosley, Thomas H; Nalls, Mike A; Oldmeadow, Christopher; Parati, Eugenio A; Psaty, Bruce M; Rothwell, Peter M; Seshadri, Sudha; Scott, Rodney J; Sharma, Pankaj; Sudlow, Cathie; Wiggins, Kerri L; Worrall, Bradford B; Rosand, Jonathan; Mitchell, Braxton D; Dichgans, Martin; Markus, Hugh S; Levi, Christopher; Attia, John; Wray, Naomi R

2015-03-01

Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses. Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA-SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles. High genetic correlation was identified between LAA and SVD using linear mixed models (rg=0.96, SE=0.47, P=9×10(-4)) and profile scores (rg=0.72; 95% confidence interval, 0.52-0.93). Between LAA and cardioembolism and SVD and cardioembolism, correlation was moderate using linear mixed models but not significantly different from zero for profile scoring. Joint meta-analysis of LAA and SVD identified strong association (P=1×10(-7)) for single nucleotide polymorphisms near the opioid receptor μ1 (OPRM1) gene. Our results suggest that LAA and SVD, which have been hitherto treated as genetically distinct, may share a substantial genetic component. Combined analyses of LAA and SVD may increase power to identify small-effect alleles influencing shared pathophysiological processes. © 2015 American Heart Association, Inc.

Risk of Guillain-Barré syndrome after 2010-2011 influenza vaccination.

PubMed

Galeotti, Francesca; Massari, Marco; D'Alessandro, Roberto; Beghi, Ettore; Chiò, Adriano; Logroscino, Giancarlo; Filippini, Graziella; Benedetti, Maria Donata; Pugliatti, Maura; Santuccio, Carmela; Raschetti, Roberto

2013-05-01

Influenza vaccination has been implicated in Guillain Barré Syndrome (GBS) although the evidence for this link is controversial. A case-control study was conducted between October 2010 and May 2011 in seven Italian Regions to explore the relation between influenza vaccination and GBS. The study included 176 GBS incident cases aged ≥18 years from 86 neurological centers. Controls were selected among patients admitted for acute conditions to the Emergency Department of the same hospital as cases. Each control was matched to a case by sex, age, Region and admission date. Two different analyses were conducted: a matched case-control analysis and a self-controlled case series analysis (SCCS). Case-control analysis included 140 cases matched to 308 controls. The adjusted matched odds ratio (OR) for GBS occurrence within 6 weeks after influenza vaccination was 3.8 (95 % CI: 1.3, 10.5). A much stronger association with gastrointestinal infections (OR = 23.8; 95 % CI 7.3, 77.6) and influenza-like illness or upper respiratory tract infections (OR = 11.5; 95 % CI 5.6, 23.5) was highlighted. The SCCS analysis included all 176 GBS cases. Influenza vaccination was associated with GBS, with a relative risk of 2.1 (95 % CI 1.1, 3.9). According to these results the attributable risk in adults ranges from two to five GBS cases per 1,000,000 vaccinations.

High Spicy Food Intake and Risk of Cancer: A Meta-analysis of Case-control Studies.

PubMed

Chen, Yu-Heng; Zou, Xiao-Nong; Zheng, Tong-Zhang; Zhou, Qi; Qiu, Hui; Chen, Yuan-Li; He, Mei; Du, Jia; Lei, Hai-Ke; Zhao, Ping

2017-09-20

Studies on the association between spicy food intake and cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on evidence from case-control studies. PubMed, EMBASE, and the Cochrane Library were searched for eligible publications. Combined odds ratios (OR s) with their 95% confidence interval (CI) were calculated using a random- or fixed-effects model. The methodological quality of the included articles was assessed using the Newcastle-Ottawa scale (NOS). All data were analyzed using STATA 11.0 software (version 11.0; StataCorp., College Station, TX, USA). Subgroup analyses were also performed with stratification by region, sex, number of cases, cancer subtype, source of the control group, and NOS score. A total 39 studies from 28 articles fulfilled the inclusion criteria for the meta-analysis (7884 patients with cancer and 10,142 controls). Comparison of the highest versus lowest exposure category in each study revealed a significant OR of 1.76 (95% CI = 1.35-2.29) in spite of significant heterogeneity (P < 0.001). In the subgroup analyses, this positive correlation was still found for gastric cancer, different regions, different numbers of cases, different sources of the control group, and high-quality articles (NOS score of ≥ 7). However, no statistically significant association was observed for women, esophageal cancer, gallbladder cancer, or low-quality articles (NOS score of <7). No evidence of publication bias was found. Evidence from case-control studies suggested that a higher level of spicy food intake may be associated with an increased incidence of cancer despite significant heterogeneity. More studies are warranted to clarify our understanding of the association between high spicy food intake and the risk of cancer.

An epidemiologic study of index and family infectious mononucleosis and adult Hodgkin's disease (HD): evidence for a specific association with EBV+ve HD in young adults.

PubMed

Alexander, Freda E; Lawrence, Davia J; Freeland, June; Krajewski, Andrew S; Angus, Brian; Taylor, G Malcolm; Jarrett, Ruth F

2003-11-01

Infectious mononucleosis (IM) is an established risk factor for Hodgkin's disease (HD). A substantial minority (33%) of cases of HD have Epstein-Barr virus (EBV) DNA within the malignant cells (are EBV+ve). It is unclear whether risk after IM applies specifically to EBV+ve HD. We report the results of a population-based case-control study of HD in adults (n = 408 cases of classical HD, 513 controls) aged 16-74 years; the case series included 113 EBV+ve and 243 EBV+ve HD. Analyses compared total HD, EBV+ve HD and EBV-ve HD with the controls and EBV+ve HD with EBV-ve HD cases using, mainly, logistic regression. Regression analyses were adjusted for gender, age-group and socioeconomic status, and were performed for the whole age range and separately for young (< 35 years) and old adults (> or = 35 years); formal tests of effect modification by age were included. For the young adults, reported IM in index or relative was strongly and significantly associated with EBV+ve HD when compared to controls (odds ratio [OR] = 2.94, 95% confidence interval [CI]: 1.08-7.98 and OR = 5.22, 95% CI: 2.15-12.68, respectively). These results may be interpreted as indications that late first exposure to EBV increases risk of HD, especially in young adults; this applies primarily to EBV+ve HD. Copyright 2003 Wiley-Liss, Inc.

A Two-Phase Case-Control Study of Autism Risk Among Children Born From the Late 1990s Through the Early 2000s in the United States.

PubMed

Geier, David A; Kern, Janet K; Geier, Mark R

2016-12-29

BACKGROUND This study evaluated the hypothesis that the 1999 recommendation by the American Academy of Pediatrics (AAP) and US Public Health Service (PHS) to reduce exposure to mercury (Hg) from Thimerosal in US vaccines would be associated with a reduction in the long-term risk of being diagnosed with autism. MATERIAL AND METHODS A two-phase assessment utilizing a case (n=73) -control (n=11,783) study in the Vaccine Adverse Event Reporting System (VAERS) database (for hypothesis generating) and a more rigorous, independent matched case (n=40) -control (n=40) study (hypothesis testing) was undertaken. RESULTS Analysis of the VAERS database using logistic regression revealed that the odds ratio (OR) for being an autism case in the VAERS database significantly decreased with a more recent year of vaccination in comparison to controls (OR=0.65) from 1998 to 2003. Sex-separated analyses revealed similar significant effects for males (OR=0.62) and females (OR=0.71). Analyses of the matched case-control data revealed, using the t-test statistic, that the mean date of birth among cases diagnosed with an autism spectrum disorder (ASD) (2000.5±1.2) was significantly more in the past than in controls (2001.1±1.3). Logistic regression also revealed that the OR for being diagnosed with ASD significantly decreased with a more recent date of birth in comparison to controls (OR=0.67) from 1998-2003. CONCLUSIONS This study reveals that the risk of autism during from the late1990s to early 2000s in the US significantly decreased with reductions in Hg exposure from Thimerosal-containing childhood vaccines, but future studies should examine this phenomenon in other US populations. Vaccine programs have significantly reduced the morbidity and mortality associated with infectious disease, but Thimerosal should be removed from all vaccines.

Multi-gene panel testing in Korean patients with common genetic generalized epilepsy syndromes.

PubMed

Lee, Cha Gon; Lee, Jeehun; Lee, Munhyang

2018-01-01

Genetic heterogeneity of common genetic generalized epilepsy syndromes is frequently considered. The present study conducted a focused analysis of potential candidate or susceptibility genes for common genetic generalized epilepsy syndromes using multi-gene panel testing with next-generation sequencing. This study included patients with juvenile myoclonic epilepsy, juvenile absence epilepsy, and epilepsy with generalized tonic-clonic seizures alone. We identified pathogenic variants according to the American College of Medical Genetics and Genomics guidelines and identified susceptibility variants using case-control association analyses and family analyses for familial cases. A total of 57 patients were enrolled, including 51 sporadic cases and 6 familial cases. Twenty-two pathogenic and likely pathogenic variants of 16 different genes were identified. CACNA1H was the most frequently observed single gene. Variants of voltage-gated Ca2+ channel genes, including CACNA1A, CACNA1G, and CACNA1H were observed in 32% of variants (n = 7/22). Analyses to identify susceptibility variants using case-control association analysis indicated that KCNMA1 c.400G>C was associated with common genetic generalized epilepsy syndromes. Only 1 family (family A) exhibited a candidate pathogenic variant p.(Arg788His) on CACNA1H, as determined via family analyses. This study identified candidate genetic variants in about a quarter of patients (n = 16/57) and an average of 2.8 variants was identified in each patient. The results reinforced the polygenic disorder with very high locus and allelic heterogeneity of common GGE syndromes. Further, voltage-gated Ca2+ channels are suggested as important contributors to common genetic generalized epilepsy syndromes. This study extends our comprehensive understanding of common genetic generalized epilepsy syndromes.

Glyphosate epidemiology expert panel review: a weight of evidence systematic review of the relationship between glyphosate exposure and non-Hodgkin's lymphoma or multiple myeloma.

PubMed

Acquavella, John; Garabrant, David; Marsh, Gary; Sorahan, Tom; Weed, Douglas L

2016-09-01

We conducted a systematic review of the epidemiologic literature for glyphosate focusing on non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) - two cancers that were the focus of a recent review by an International Agency for Research on Cancer Working Group. Our approach was consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews. We evaluated each relevant study according to a priori criteria for study quality: adequacy of study size, likelihood of confounding, potential for other biases and adequacy of the statistical analyses. Our evaluation included seven unique studies for NHL and four for MM, all but one of which were case control studies for each cancer. For NHL, the case-control studies were all limited by the potential for recall bias and the lack of adequate multivariate adjustment for multiple pesticide and other farming exposures. Only the Agricultural Health (cohort) Study met our a priori quality standards and this study found no evidence of an association between glyphosate and NHL. For MM, the case control studies shared the same limitations as noted for the NHL case-control studies and, in aggregate, the data were too sparse to enable an informed causal judgment. Overall, our review did not find support in the epidemiologic literature for a causal association between glyphosate and NHL or MM.

Migration-related tuberculosis: epidemiology and characteristics of tuberculosis cases originating outside the European Union and European Economic Area, 2007 to 2013.

PubMed

Ködmön, Csaba; Zucs, Phillip; van der Werf, Marieke J

2016-01-01

Migrants arriving from high tuberculosis (TB)-incidence countries may pose a significant challenge to TB control programmes in the host country. TB surveillance data for 2007-2013 submitted to the European Surveillance System were analysed. Notified TB cases were stratified by origin and reporting country. The contribution of migrant TB cases to the TB epidemiology in EU/EEA countries was analysed. Migrant TB cases accounted for 17.4% (n = 92,039) of all TB cases reported in the EU/EEA in 2007-2013, continuously increasing from 13.6% in 2007 to 21.8% in 2013. Of 91,925 migrant cases with known country of origin, 29.3% were from the Eastern Mediterranean, 23.0% from south-east Asia, 21.4% from Africa, 13.4% from the World Health Organization European Region (excluding EU/EEA), and 12.9% from other regions. Of 46,499 migrant cases with known drug-susceptibility test results, 2.9% had multidrug-resistant TB, mainly (51.7%) originating from the European Region. The increasing contribution of TB in migrants from outside the EU/EEA to the TB burden in the EU/EEA is mainly due to a decrease in native TB cases. Especially in countries with a high proportion of TB cases in non-EU/EEA migrants, targeted prevention and control initiatives may be needed to progress towards TB elimination.

Epidemiologic programs for computers and calculators. A microcomputer program for multiple logistic regression by unconditional and conditional maximum likelihood methods.

PubMed

Campos-Filho, N; Franco, E L

1989-02-01

A frequent procedure in matched case-control studies is to report results from the multivariate unmatched analyses if they do not differ substantially from the ones obtained after conditioning on the matching variables. Although conceptually simple, this rule requires that an extensive series of logistic regression models be evaluated by both the conditional and unconditional maximum likelihood methods. Most computer programs for logistic regression employ only one maximum likelihood method, which requires that the analyses be performed in separate steps. This paper describes a Pascal microcomputer (IBM PC) program that performs multiple logistic regression by both maximum likelihood estimation methods, which obviates the need for switching between programs to obtain relative risk estimates from both matched and unmatched analyses. The program calculates most standard statistics and allows factoring of categorical or continuous variables by two distinct methods of contrast. A built-in, descriptive statistics option allows the user to inspect the distribution of cases and controls across categories of any given variable.

Type II diabetes mellitus and incident osteoarthritis of the hand: a population-based case-control analysis.

PubMed

Frey, N; Hügle, T; Jick, S S; Meier, C R; Spoendlin, J

2016-09-01

Emerging evidence suggests that diabetes may be a risk factor for osteoarthritis (OA). However, previous results on the association between diabetes and all OA were conflicting. We aimed to comprehensively analyse the association between type II diabetes mellitus (T2DM) and osteoarthritis of the hand (HOA) specifically. We conducted a matched (1:1) case-control study using the UK-based Clinical Practice Research Datalink (CPRD) of cases aged 30-90 years with an incident diagnosis of HOA from 1995 to 2013. In multivariable conditional logistic regression analyses, we calculated odds ratios (OR) for incident HOA in patients with T2DM, categorized by T2DM severity (HbA1C), duration, and pharmacological treatment. We further performed sensitivity analyses in patients with and without other metabolic diseases (hypertension (HT), hyperlipidaemia (HL), obesity). Among 13,500 cases and 13,500 controls, we observed no statistically significant association between T2DM and HOA (OR 0.95, 95% confidence interval (CI) 0.87-1.04), regardless of T2DM severity, duration, or pharmacological treatment. Having HT did not change the OR. Although we observed slightly increased ORs in overweight T2DM patients with co-occurring HL with or without coexisting HT, none of these ORs were statistically significant. Our results provide evidence that T2DM is not an independent risk factor for HOA. Concurrence of T2DM with HT, HL, and/or obesity did not change this association significantly. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Continuing difficulties in interpreting CNV data: lessons from a genome-wide CNV association study of Australian HNPCC/lynch syndrome patients.

PubMed

Talseth-Palmer, Bente A; Holliday, Elizabeth G; Evans, Tiffany-Jane; McEvoy, Mark; Attia, John; Grice, Desma M; Masson, Amy L; Meldrum, Cliff; Spigelman, Allan; Scott, Rodney J

2013-03-26

Hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome (LS) is a cancer syndrome characterised by early-onset epithelial cancers, especially colorectal cancer (CRC) and endometrial cancer. The aim of the current study was to use SNP-array technology to identify genomic aberrations which could contribute to the increased risk of cancer in HNPCC/LS patients. Individuals diagnosed with HNPCC/LS (100) and healthy controls (384) were genotyped using the Illumina Human610-Quad SNP-arrays. Copy number variation (CNV) calling and association analyses were performed using Nexus software, with significant results validated using QuantiSNP. TaqMan Copy-Number assays were used for verification of CNVs showing significant association with HNPCC/LS identified by both software programs. We detected copy number (CN) gains associated with HNPCC/LS status on chromosome 7q11.21 (28% cases and 0% controls, Nexus; p =3.60E-20 and QuantiSNP; p < 1.00E-16) and 16p11.2 (46% in cases, while a CN loss was observed in 23% of controls, Nexus; p = 4.93E-21 and QuantiSNP; p = 5.00E-06) via in silico analyses. TaqMan Copy-Number assay was used for validation of CNVs showing significant association with HNPCC/LS. In addition, CNV burden (total CNV length, average CNV length and number of observed CNV events) was significantly greater in cases compared to controls. A greater CNV burden was identified in HNPCC/LS cases compared to controls supporting the notion of higher genomic instability in these patients. One intergenic locus on chromosome 7q11.21 is possibly associated with HNPCC/LS and deserves further investigation. The results from this study highlight the complexities of fluorescent based CNV analyses. The inefficiency of both CNV detection methods to reproducibly detect observed CNVs demonstrates the need for sequence data to be considered alongside intensity data to avoid false positive results.

Clinical Research Methodology 2: Observational Clinical Research.

PubMed

Sessler, Daniel I; Imrey, Peter B

2015-10-01

Case-control and cohort studies are invaluable research tools and provide the strongest feasible research designs for addressing some questions. Case-control studies usually involve retrospective data collection. Cohort studies can involve retrospective, ambidirectional, or prospective data collection. Observational studies are subject to errors attributable to selection bias, confounding, measurement bias, and reverse causation-in addition to errors of chance. Confounding can be statistically controlled to the extent that potential factors are known and accurately measured, but, in practice, bias and unknown confounders usually remain additional potential sources of error, often of unknown magnitude and clinical impact. Causality-the most clinically useful relation between exposure and outcome-can rarely be definitively determined from observational studies because intentional, controlled manipulations of exposures are not involved. In this article, we review several types of observational clinical research: case series, comparative case-control and cohort studies, and hybrid designs in which case-control analyses are performed on selected members of cohorts. We also discuss the analytic issues that arise when groups to be compared in an observational study, such as patients receiving different therapies, are not comparable in other respects.

Validation of the Cepstral Spectral Index of Dysphonia (CSID) as a Screening Tool for Voice Disorders: Development of Clinical Cutoff Scores.

PubMed

Awan, Shaheen N; Roy, Nelson; Zhang, Dong; Cohen, Seth M

2016-03-01

The purposes of this study were to (1) evaluate the performance of the Cepstral Spectral Index of Dysphonia (CSID--a multivariate estimate of dysphonia severity) as a potential screening tool for voice disorder identification and (2) identify potential clinical cutoff scores to classify voice-disordered cases versus controls. Subjects were 332 men and women (116 men, 216 women) comprised of subjects who presented to a physician with a voice-related complaint and a group of non-voice-related control subjects. Voice-disordered cases versus controls were initially defined via three reference standards: (1) auditory-perceptual judgment (dysphonia +/-); (2) Voice Handicap Index (VHI) score (VHI +/-); and (3) laryngoscopic description (laryngoscopic +/-). Speech samples were analyzed using the Analysis of Dysphonia in Speech and Voice program. Cepstral and spectral measures were combined into a CSID multivariate formula which estimated dysphonia severity for Rainbow Passage samples (i.e., the CSIDR). The ability of the CSIDR to accurately classify cases versus controls in relation to each reference standard was evaluated via a combination of logistic regression and receiver operating characteristic (ROC) analyses. The ability of the CSIDR to discriminate between cases and controls was represented by the "area under the ROC curve" (AUC). ROC classification of dysphonia-positive cases versus controls resulted in a strong AUC = 0.85. A CSIDR cutoff of ≈24 achieved the best balance between sensitivity and specificity, whereas a more liberal cutoff score of ≈19 resulted in higher sensitivity while maintaining respectable specificity which may be preferred for screening purposes. Weaker but adequate AUCs = 0.75 and 0.73 were observed for the classification of VHI-positive and laryngoscopic-positive cases versus controls, respectively. Logistic regression analyses indicated that subject age may be a significant covariate in the discrimination of dysphonia-positive and VHI-positive cases versus controls. The CSIDR can provide a strong level of accuracy for the classification of voice-disordered cases versus controls, particularly when auditory-perceptual judgment is used as the reference standard. Although users often focus on a cutoff score that achieves a balance between sensitivity and specificity, more liberal cutoffs for screening purposes versus conservative cutoffs when cost or risk of further evaluation is deemed to be high should also be considered. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Risk of Psychiatric and Neurodevelopmental Disorders Among Siblings of Probands With Autism Spectrum Disorders.

PubMed

Jokiranta-Olkoniemi, Elina; Cheslack-Postava, Keely; Sucksdorff, Dan; Suominen, Auli; Gyllenberg, David; Chudal, Roshan; Leivonen, Susanna; Gissler, Mika; Brown, Alan S; Sourander, Andre

2016-06-01

Previous research has focused on examining the familial clustering of schizophrenia, bipolar disorder, and autism spectrum disorders (ASD). Little is known about the clustering of other psychiatric and neurodevelopmental disorders among siblings of persons with ASD. To examine the risk for psychiatric and neurodevelopmental disorders among full siblings of probands with ASD. The Finnish Prenatal Study of Autism and Autism Spectrum Disorders used a population-based cohort that included children born from January 1, 1987, to December 31, 2005, who received a diagnosis of ASD by December 31, 2007. Each case was individually matched to 4 control participants by sex and date and place of birth. The siblings of the cases and controls were born from January 1, 1977, to December 31, 2005, and received a diagnosis from January 1, 1987, to December 31, 2009. This nested case-control study included 3578 cases with ASD with 6022 full siblings and 11 775 controls with 22 127 siblings from Finnish national registers. Data were analyzed from March 6, 2014, to February 12, 2016. The adjusted risk ratio (RR) for psychiatric and neurodevelopmental disorders among siblings of probands with ASD vs siblings of matched controls. Additional analyses were conducted separately for ASD subgroups, including childhood autism, Asperger syndrome, and pervasive developmental disorders not otherwise specified. Analyses were further stratified by sex and intellectual disability among the probands. Among the 3578 cases with ASD (2841 boys [79.4%]) and 11 775 controls (9345 boys [79.4%]), 1319 cases (36.9%) and 2052 controls (17.4%) had at least 1 sibling diagnosed with any psychiatric or neurodevelopmental disorder (adjusted RR, 2.5; 95% CI, 2.3-2.6). The largest associations were observed for childhood-onset disorders (1061 cases [29.7%] vs 1362 controls [11.6%]; adjusted RR, 3.0; 95% CI, 2.8-3.3), including ASD (374 cases [10.5%] vs 125 controls [1.1%]; adjusted RR, 11.8; 95% CI, 9.4-14.7), tic disorders (28 cases [0.8%] vs 24 controls [0.2%]; adjusted RR, 4.3; 95% CI, 2.3-8.2), attention-deficit/hyperactivity disorder (189 cases [5.3%] vs 180 controls [1.5%]; adjusted RR, 3.7; 95% CI, 2.9-4.7), learning and coordination disorders (563 cases [15.7%] vs 697 controls [5.9%]; adjusted RR, 3.2; 95% CI, 2.8-3.6), intellectual disability (104 cases [2.9%] vs 137 controls [1.2%]; adjusted RR, 3.1; 95% CI, 2.3-4.2), conduct and oppositional disorders (180 cases [5.0%] vs 221 controls [1.9%]; adjusted RR, 2.8; 95% CI, 2.2-3.5), and emotional disorders with onset specific to childhood (126 cases [3.5%] vs 157 controls [1.3%]; adjusted RR, 2.6; 95% CI, 1.9-3.4). Autism spectrum disorders were also associated with schizophrenia spectrum disorders, affective disorders, anxiety disorders, and other neurotic and personality disorders among siblings. Psychiatric and neurodevelopmental disorders cluster among siblings of probands with ASD. For etiologic research, these findings provide further evidence that several psychiatric and neurodevelopmental disorders have common risk factors.

Correcting for batch effects in case-control microbiome studies

PubMed Central

Gibbons, Sean M.; Duvallet, Claire

2018-01-01

High-throughput data generation platforms, like mass-spectrometry, microarrays, and second-generation sequencing are susceptible to batch effects due to run-to-run variation in reagents, equipment, protocols, or personnel. Currently, batch correction methods are not commonly applied to microbiome sequencing datasets. In this paper, we compare different batch-correction methods applied to microbiome case-control studies. We introduce a model-free normalization procedure where features (i.e. bacterial taxa) in case samples are converted to percentiles of the equivalent features in control samples within a study prior to pooling data across studies. We look at how this percentile-normalization method compares to traditional meta-analysis methods for combining independent p-values and to limma and ComBat, widely used batch-correction models developed for RNA microarray data. Overall, we show that percentile-normalization is a simple, non-parametric approach for correcting batch effects and improving sensitivity in case-control meta-analyses. PMID:29684016

Factors Associated with Pleurisy in Pigs: A Case-Control Analysis of Slaughter Pig Data for England and Wales

PubMed Central

Jäger, Henrike C.; McKinley, Trevelyan J.; Wood, James L. N.; Pearce, Gareth P.; Williamson, Susanna; Strugnell, Benjamin; Done, Stanley; Habernoll, Henrike; Palzer, Andreas; Tucker, Alexander W.

2012-01-01

A case-control investigation was undertaken to determine management and health related factors associated with pleurisy in slaughter pigs in England and Wales. Methods The British Pig Executive Pig Health Scheme database of abattoir pathology was used to identify 121 case (>10% prevalence of pleurisy on 3 or more assessment dates in the preceding 24 months) and 121 control units (≤5% prevalence of pleurisy on 3 or more assessment dates in the preceding 24 months). Farm data were collected by postal questionnaire. Data from respondents (70 cases and 51 controls) were analysed using simple logistic regression models with Bonferroni corrections. Limited multivariate analyses were also performed to check the robustness of the overall conclusions. Results and Conclusions Management factors associated with increased odds of pleurisy included no all-in all-out pig flow (OR 9.3, 95% confidence interval [CI]: 3.3–29), rearing of pigs with an age difference of >1 month in the same airspace (OR 6.5 [2.8–17]) and repeated mixing (OR 2.2 [1.4–3.8]) or moving (OR 2.2 [1.5–3.4]) of pigs during the rearing phase. Those associated with decreased odds of pleurisy included filling wean-to-finish or grower-to-finish systems with piglets from ≤3 sources (OR 0.18 [0.07–0.41]) compared to farrow-to-finish systems, cleaning and disinfecting of grower (ORs 0.28 [0.13–0.61] and 0.29 [0.13–0.61]) and finisher (ORs 0.24 [0.11–0.51] and 0.2 [0.09–0.44]) accommodation between groups, and extended down time of grower and finisher accommodation (OR 0.84 [0.75–0.93] and 0.86 [0.77–0.94] respectively for each additional day of downtime). This study demonstrated the value of national-level abattoir pathology data collection systems for case control analyses and generated guidance for on-farm interventions to help reduce the prevalence of pleurisy in slaughter pigs. PMID:22363407

Changes in renal function after discontinuation of vitamin D analogues in advanced chronic kidney disease.

PubMed

Caravaca, Francisco; Caravaca-Fontán, Fernando; Azevedo, Lilia; Luna, Enrique

In routine clinical practice, the prescription of vitamin D analogues (VDA) in patients with chronic kidney disease (CKD) is often associated with a decline of the estimated renal function. The reason for this is not fully understood. To analyse the effects of VDA discontinuation in advanced CKD and to determine the factors associated with changes in renal function. Retrospective cohort study of adult patients with advanced CKD. The case subgroup was treated with VDA and this medication was discontinued at baseline (the first visit). The control subgroup was not treated with VDA and they were selected according to comparability principles for CKD progression by propensity score matching. The primary outcome measure was a change to both the estimated glomerular filtration rate (MDRD-GFR) and the measured glomerular filtration rate (mGFR by combined creatinine and urea clearances). Baseline parameters related to mineral metabolism and creatinine generation were analysed as potential determinants of renal function changes. The study sample consisted of 67 cases and 67 controls. Renal function improved in 67% of cases and worsened in 72% of controls (p<0.0001). Changes in MDRD-GFR for the case subgroup and the control subgroup were +0.455±0.997 vs. -0.436±1.103ml/min/1.73 m 2 /month (p<0.0001), respectively. Total creatinine excretion was slightly higher in cases than in controls but the difference was not significant. According to multivariate logistic and linear regression analyses, baseline total serum calcium was one of the best determinants of both renal function recovery (Odds ratio=3.49; p=0.001), and of the extent of renal function recovery (beta=0.276; p=0.001). Discontinuation of VDA treatment in CKD patients is associated with significant recovery of estimated renal function. The extent of these changes is mainly associated with baseline total serum calcium. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Meta-analyses of the Association of Sleep Apnea with Insulin Resistance, and the Effects of CPAP on HOMA-IR, Adiponectin, and Visceral Adipose Fat

PubMed Central

Iftikhar, Imran H.; Hoyos, Camilla M.; Phillips, Craig L.; Magalang, Ulysses J.

2015-01-01

Objective: We sought to conduct an updated meta-analysis of randomized controlled trials (RCTs) on the effect of continuous positive airway pressure (CPAP) on insulin resistance, as measured by homeostasis model assessment of insulin resistance (HOMA-IR), visceral abdominal fat (VAF), and adiponectin. Additionally, we performed a separate meta-analysis and meta-regression of studies on the association of insulin resistance and obstructive sleep apnea (OSA). Methods: All included studies were searched from PubMed (from conception to March 15, 2014). Data were pooled across all included RCTs as the mean difference in HOMA-IR and VAF, and as the standardized mean difference in the case of adiponectin analysis. From the included case-control studies, data on the difference of HOMA-IR between cases and controls were pooled across all studies, as the standardized mean difference (SMD). Results: There was a significant difference in HOMA-IR (−0.43 [95% CIs: −0.75 to −0.11], p = 0.008) between CPAP treated and non CPAP treated participants. However, there was no significant difference in VAF or adiponectin; (−47.93 [95% CI: −112.58 to 16.72], p = 0.14) and (−0.06 [95% CI: −0.28 to 0.15], p = 0.56), respectively. Meta-analysis of 16 case-control studies showed a pooled SMD in HOMA-IR of 0.51 (95% CI: 0.28 to 0.75), p ≤ 0.001, between cases and controls. Conclusions: The results of our meta-analyses show that CPAP has a favorable effect on insulin resistance. This effect is not associated with any significant changes in total adiponectin levels or amount of VAF. Our findings also confirm a significant association between OSA and insulin resistance. Citation: Iftikhar IH, Hoyos CM, Phillips CL, Magalang UJ. Meta-analyses of the association of sleep apnea with insulin resistance, and the effects of CPAP on HOMA-IR, adiponectin, and visceral adipose fat. J Clin Sleep Med 2015;11(4):475–485. PMID:25700870

Statin use and risk of cholecystectomy - A case-control analysis using Swiss claims data.

PubMed

Biétry, Fabienne A; Reich, Oliver; Schwenkglenks, Matthias; Meier, Christoph R

2016-12-01

Using claims data from the Helsana Group, a large Swiss health insurance provider, we examined the association between statin use and the risk of cholecystectomy in a case-control analysis. We identified 2,200 cholecystectomy cases between 2013 and 2014 and matched 4 controls to each case on age, sex, index date and canton. We categorized statin users into current or past users (last prescription ≤ 180 or > 180 days before the index date, respectively) and classified medication use by duration based on number of prescriptions before the index date. We applied conditional logistic regression analyses to calculate odds ratios (ORs) with 95% confidence intervals (CIs) and adjusted the analyses for history of cardiovascular diseases and for use of estrogens, fibrates and other lipid-lowering agents. The adjusted OR (aOR) for cholecystectomy was 0.85 (95% CI: 0.74, 0.99) for current statin users compared to non-users. Long-term current statin use (5-19 prescriptions) was associated with a reduced OR (aOR 0.77, 95% CI: 0.65, 0.92). However, neither short-term current use nor past statin use affected the risk of cholecystectomy. The study supports the previously raised hypothesis that long-term statin use reduces the risk of cholecystectomy.

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

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.

Effects of the X:IT smoking intervention: a school-based cluster randomized trial.

PubMed

Andersen, Anette; Krølner, Rikker; Bast, Lotus Sofie; Thygesen, Lau Caspar; Due, Pernille

2015-12-01

Uptake of smoking in adolescence is still of major public health concern. Evaluations of school-based programmes for smoking prevention show mixed results. The aim of this study was to examine the effect of X:IT, a multi-component school-based programme to prevent adolescent smoking. Data from a Danish cluster randomized trial included 4041 year-7 students (mean age: 12.5) from 51 intervention and 43 control schools. Outcome measure 'current smoking' was dichotomized into smoking daily, weekly, monthly or more seldom vs do not smoke. Analyses were adjusted for baseline covariates: sex, family socioeconomic position (SEP), best friend's smoking and parental smoking. We performed multilevel, logistic regression analyses of available cases and intention-to-treat (ITT) analyses, replacing missing outcome values by multiple imputation. At baseline, 4.7% and 6.8% of the students at the intervention and the control schools smoked, respectively. After 1 year of the intervention, the prevalence was 7.9% and 10.7%, respectively. At follow-up, 553 students (13.7%) did not answer the question on smoking. Available case analyses: crude odds ratios (OR) for smoking at intervention schools compared with control schools: 0.65 (0.48-0.88) and adjusted: 0.70 (0.47-1.04). ITT analyses: crude OR for smoking at intervention schools compared with control schools: 0.67 (0.50-0.89) and adjusted: 0.61 (0.45-0.82). Students at intervention schools had a lower risk of smoking after a year of intervention in year 7. This multi-component intervention involving educational, parental and context-related intervention components seems to be efficient in lowering or postponing smoking uptake in Danish adolescents. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

An Outbreak of Cryptosporidium parvum across England & Scotland Associated with Consumption of Fresh Pre-Cut Salad Leaves, May 2012

PubMed Central

McKerr, Caoimhe; Adak, Goutam K.; Nichols, Gordon; Gorton, Russell; Chalmers, Rachel M.; Kafatos, George; Cosford, Paul; Charlett, Andre; Reacher, Mark; Pollock, Kevin G.; Alexander, Claire L.; Morton, Stephen

2015-01-01

Background We report a widespread foodborne outbreak of Cryptosporidium parvum in England and Scotland in May 2012. Cases were more common in female adults, and had no history of foreign travel. Over 300 excess cases were identified during the period of the outbreak. Speciation and microbiological typing revealed the outbreak strain to be C. parvum gp60 subtype IIaA15G2R1. Methods Hypothesis generation questionnaires were administered and an unmatched case control study was undertaken to test the hypotheses raised. Cases and controls were interviewed by telephone. Controls were selected using sequential digit dialling. Information was gathered on demographics, foods consumed and retailers where foods were purchased. Results Seventy-four laboratory confirmed cases and 74 controls were included in analyses. Infection was found to be strongly associated with the consumption of pre-cut mixed salad leaves sold by a single retailer. This is the largest documented outbreak of cryptosporidiosis attributed to a food vehicle. PMID:26017538

An Outbreak of Cryptosporidium parvum across England & Scotland Associated with Consumption of Fresh Pre-Cut Salad Leaves, May 2012.

PubMed

McKerr, Caoimhe; Adak, Goutam K; Nichols, Gordon; Gorton, Russell; Chalmers, Rachel M; Kafatos, George; Cosford, Paul; Charlett, Andre; Reacher, Mark; Pollock, Kevin G; Alexander, Claire L; Morton, Stephen

2015-01-01

We report a widespread foodborne outbreak of Cryptosporidium parvum in England and Scotland in May 2012. Cases were more common in female adults, and had no history of foreign travel. Over 300 excess cases were identified during the period of the outbreak. Speciation and microbiological typing revealed the outbreak strain to be C. parvum gp60 subtype IIaA15G2R1. Hypothesis generation questionnaires were administered and an unmatched case control study was undertaken to test the hypotheses raised. Cases and controls were interviewed by telephone. Controls were selected using sequential digit dialling. Information was gathered on demographics, foods consumed and retailers where foods were purchased. Seventy-four laboratory confirmed cases and 74 controls were included in analyses. Infection was found to be strongly associated with the consumption of pre-cut mixed salad leaves sold by a single retailer. This is the largest documented outbreak of cryptosporidiosis attributed to a food vehicle.

Lung cancer risk among workers in the construction industry: results from two case-control studies in Montreal.

PubMed

Lacourt, Aude; Pintos, Javier; Lavoué, Jérôme; Richardson, Lesley; Siemiatycki, Jack

2015-09-22

Given the large number of workers in the construction industry, it is important to derive accurate and valid estimates of cancer risk, and in particular lung cancer risk. In most previous studies, risks among construction workers were compared with general populations including blue and white collar workers. The main objectives of this study were to assess whether construction workers experience excess lung cancer risk, and whether exposure to selected construction industry exposures carries excess risks. We wished to address these objectives within the sub-population of blue collar workers. Two case-control studies were conducted in Montreal. Combined, they included 1593 lung cancer cases and 1427 controls, of whom 1304 cases and 1081 controls had been blue collar workers. Detailed lifetime job histories were obtained and translated by experts into histories of exposure to chemical agents. The two key analyses were to estimate odds ratio (OR) estimates of lung cancer risk: a) for all blue-collar construction workers compared with other blue-collar workers, and b) for construction workers exposed to each of 20 exposure agents found in the construction industry compared with construction workers unexposed to those agents. All analyses were conducted using unconditional logistic regression adjusted for socio-demographic factors and smoking history. The OR for all construction workers combined was 1.11 (95 % CI: 0.90-1.38), based on 381 blue collar construction workers. Analyses of specific exposures were hampered by small numbers and imprecise estimates. While none of 20 occupational agents examined was significantly associated with lung cancer, the following agents manifested non-significantly elevated ORs: asbestos, silica, Portland cement, soil dust, calcium oxide and calcium sulfate. Compared with other blue collar workers, there was only a slight increased risk of lung cancer for subjects who ever held an occupation in the construction industry. The analyses of agents within the construction industry produced imprecise estimates of risk, but nevertheless pointed to some plausible associations. Excess risks for asbestos and silica were in line with previous knowledge. The possible excess risks with the other inorganic dusts require further corroboration.

Evaluation of optimal water fluoridation on the incidence and skeletal distribution of naturally arising osteosarcoma in pet dogs

PubMed Central

Rebhun, R. B.; Kass, P. H.; Kent, M. S.; Watson, K. D.; Withers, S. S.; Culp, W. T. N.; King, A.M.

2016-01-01

Experimental toxicological studies in laboratory animals and epidemiological human studies have reported a possible association between water fluoridation and osteosarcoma (OSA). To further explore this possibility, a case-control study of individual dogs evaluated by the UC Davis Veterinary Medical Teaching Hospital was conducted using ecologic data on water fluoridation based on the owner’s residence. The case group included 161 dogs with OSA diagnosed between 2008–2012. Two cancer control groups included dogs diagnosed with lymphoma (LSA) or hemangiosarcoma (HSA) during the same period (n = 134 and n = 145, respectively). Dogs with OSA were not significantly more likely to live in an area with optimized fluoride in the water than dogs with LSA or HSA. Additional analyses within OSA patients also revealed no significant differences in age, or skeletal distribution of OSA cases relative to fluoride status. Taken together, these analyses do not support the hypothesis that optimal fluoridation of drinking water contributes to naturally occurring OSA in dogs. PMID:26762869

Evaluation of optimal water fluoridation on the incidence and skeletal distribution of naturally arising osteosarcoma in pet dogs.

PubMed

Rebhun, R B; Kass, P H; Kent, M S; Watson, K D; Withers, S S; Culp, W T N; King, A M

2017-06-01

Experimental toxicological studies in laboratory animals and epidemiological human studies have reported a possible association between water fluoridation and osteosarcoma (OSA). To further explore this possibility, a case-control study of individual dogs evaluated by the UC Davis Veterinary Medical Teaching Hospital was conducted using ecologic data on water fluoridation based on the owner's residence. The case group included 161 dogs with OSA diagnosed between 2008-2012. Two cancer control groups included dogs diagnosed with lymphoma (LSA) or hemangiosarcoma (HSA) during the same period (n = 134 and n = 145, respectively). Dogs with OSA were not significantly more likely to live in an area with optimized fluoride in the water than dogs with LSA or HSA. Additional analyses within OSA patients also revealed no significant differences in age, or skeletal distribution of OSA cases relative to fluoride status. Taken together, these analyses do not support the hypothesis that optimal fluoridation of drinking water contributes to naturally occurring OSA in dogs. © 2016 John Wiley & Sons Ltd.

Caries Experience in Children with and without Molar-Incisor Hypomineralisation: A Case-Control Study.

PubMed

Grossi, Juliana de Aguiar; Cabral, Renata Nunes; Leal, Soraya Coelho

2017-01-01

The aim of this study was to compare the caries experience of children with and without molar-incisor hypomineralisation (MIH). A case-control study was designed in which 130 children aged between 7 and 13 years with MIH (cases) were matched with 130 children without the condition (controls) according to age, sex, and school. Dental caries and MIH were assessed using the Caries Assessment Spectrum and Treatment (CAST) and European Academy of Paediatric Dentistry (EAPD) criteria, respectively, by three examiners. CAST was converted into DMFT/dmft; the Kruskal-Wallis test was performed to analyse whether dmft/DMFT was influenced by the severity of MIH. Associations between MIH and dental caries were analysed at child and tooth levels: between and within subjects, respectively. To correlate MIH severity and the occurrence of dental caries, the Cochran-Armitage test was used. The mean age of the children was 9.63 ± 1.29 years. The mean dmft for cases was 1.23 ± 1.99 and for controls 1.71 ± 2.22 (p > 0.05). For the DMFT, the mean scores for cases and controls were 0.45 ± 0.90 and 0.07 ± 0.25, respectively (p < 0.001). The between-subject analysis showed no difference in relation to enamel carious lesions; however, the prevalence of dentine carious lesions was significantly higher in children with MIH than in those without the condition. The same pattern was seen for the within-subject analysis. It was observed that the increase in MIH severity resulted in more teeth being affected by dentine carious lesions (p = 0.0003). Children with MIH presented a higher experience of caries in the permanent dentition than those without the condition. MIH was considered a risk factor for caries development. © 2017 S. Karger AG, Basel.

Fluid balance and chloride load in the first 24h of ICU admission and its relation with renal replacement therapies through a multicentre, retrospective, case-control study paired by APACHE-II.

PubMed

González-Castro, A; Ortiz-Lasa, M; Leizaola, O; Salgado, E; Irriguible, T; Sánchez-Satorra, M; Lomas-Fernández, C; Barral-Segade, P; Cordero-Vallejo, M; Rodrigo-Calabia, E; Dierssen-Sotos, T

2017-05-01

To analyse the association between water balance during the first 24h of admission to ICU and the variables related to chloride levels (chloride loading, type of fluid administered, hyperchloraemia), with the development of acute kidney injury renal replacement therapy (AKI-RRT) during patients' admission to ICU. Multicentre case-control study. Hospital-based, national, carried out in 6 ICUs. Cases were patients older than 18 years who developed an AKI-RRT. Controls were patients older than 18 years admitted to the same institutions during the study period, who did not develop AKI-RRT during ICU admission. Pairing was done by APACHE-II. An analysis of unconditional logistic regression adjusted for age, sex, APACHE-II and water balance (in evaluating the type of fluid). We analysed the variables of 430 patients: 215 cases and 215 controls. An increase of 10% of the possibility of developing AKI-RRT per 500ml of positive water balance was evident (OR: 1.09 [95% CI: 1.05 to 1.14]; P<.001). The study of mean values of chloride load administered did not show differences between the group of cases and controls (299.35±254.91 vs. 301.67±234.63; P=.92). The water balance in the first 24h of ICU admission relates to the development of IRA-TRR, regardless of chloraemia. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Meta-analyses of the Association of Sleep Apnea with Insulin Resistance, and the Effects of CPAP on HOMA-IR, Adiponectin, and Visceral Adipose Fat.

PubMed

Iftikhar, Imran H; Hoyos, Camilla M; Phillips, Craig L; Magalang, Ulysses J

2015-04-15

We sought to conduct an updated meta-analysis of randomized controlled trials (RCTs) on the effect of continuous positive airway pressure (CPAP) on insulin resistance, as measured by homeostasis model assessment of insulin resistance (HOMA-IR), visceral abdominal fat (VAF), and adiponectin. Additionally, we performed a separate meta-analysis and meta-regression of studies on the association of insulin resistance and obstructive sleep apnea (OSA). All included studies were searched from PubMed (from conception to March 15, 2014). Data were pooled across all included RCTs as the mean difference in HOMA-IR and VAF, and as the standardized mean difference in the case of adiponectin analysis. From the included case-control studies, data on the difference of HOMA-IR between cases and controls were pooled across all studies, as the standardized mean difference (SMD). There was a significant difference in HOMA-IR (-0.43 [95% CIs: -0.75 to -0.11], p = 0.008) between CPAP treated and non CPAP treated participants. However, there was no significant difference in VAF or adiponectin; (-47.93 [95% CI: -112.58 to 16.72], p = 0.14) and (-0.06 [95% CI: -0.28 to 0.15], p = 0.56), respectively. Meta-analysis of 16 case-control studies showed a pooled SMD in HOMA-IR of 0.51 (95% CI: 0.28 to 0.75), p ≤ 0.001, between cases and controls. The results of our meta-analyses show that CPAP has a favorable effect on insulin resistance. This effect is not associated with any significant changes in total adiponectin levels or amount of VAF. Our findings also confirm a significant association between OSA and insulin resistance. © 2015 American Academy of Sleep Medicine.

Parental occupational paint exposure and risk of childhood leukemia in the offspring: Findings from the Childhood Leukemia International Consortium

PubMed Central

Bailey, Helen D; Fritschi, Lin; Metayer, Catherine; Infante-Rivard, Claire; Magnani, Corrado; Petridou, Eleni; Roman, Eve; Spector, Logan G; Kaatsch, Peter; Clavel, Jacqueline; Milne, Elizabeth; Dockerty, John D; Glass, Deborah C; Lightfoot, Tracy; Miligi, Lucia; Rudant, Jérémie; Baka, Margarita; Rondelli, Roberto; Amigou, Alicia; Simpson, Jill; Kang, Alice; Moschovi, Maria; Schüz, Joachim

2014-01-01

Purpose It has been suggested that parental occupational paint exposure around the time of conception or pregnancy increases the risk of childhood leukemia in the offspring. Methods We obtained individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium (CLIC). Occupational data were harmonized to a compatible format. Meta-analyses of study-specific odds ratios (ORs) were undertaken, as well as pooled analyses of individual data using unconditional logistic regression. Results Using individual data from fathers of 8,185 cases and 14,210 controls, the pooled OR for paternal exposure around conception and risk of acute lymphoblastic leukaemia (ALL) was 0.93 (95% confidence interval (CI) 0.76, 1.14). Analysis of data from 8,156 ALL case mothers and 14,568 control mothers produced a pooled OR of 0.81 (95% CI 0.39, 1.68) for exposure during pregnancy. For acute myeloid leukaemia (AML), the pooled ORs for paternal and maternal exposure were 0.96 (95% CI 0.65, 1.41) and 1.31 (95% CI 0.38, 4.47) respectively, based on data from 1,231 case and 11,392 control fathers and 1,329 case and 12,141 control mothers. Heterogeneity among the individual studies ranged from low to modest. Conclusions Null findings for paternal exposure for both ALL and AML are consistent with previous reports. Despite the large sample size, results for maternal exposure to paints in pregnancy were based on small numbers of exposed. Overall, we found no evidence that parental occupational exposure to paints increases the risk of leukemia in the offspring, but further data on home exposure are needed. PMID:25088805

Differential Diagnosis of Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder by Means of Inhibitory Control and "Theory of Mind"

ERIC Educational Resources Information Center

Buhler, Eva; Bachmann, Christian; Goyert, Hannah; Heinzel-Gutenbrunner, Monika; Kamp-Becker, Inge

2011-01-01

Autism spectrum disorders (ASD) and attention deficit hyperactivity disorders (ADHD) are both associated with deficits in executive control and with problems in social contexts. This study analyses the variables inhibitory control and theory of mind (ToM), including a developmental aspect in the case of the latter, to differentiate between the…

Cerebrovascular accidents in elderly people treated with antipsychotic drugs: a systematic review.

PubMed

Sacchetti, Emilio; Turrina, Cesare; Valsecchi, Paolo

2010-04-01

After 2002, an association between stroke and antipsychotic use was reported in clinical trials and large database studies. This review considers previous quantitative reviews, newly published clinical trials, and recent observational cohort and case-control studies, and focuses on the clinical significance of the risk for stroke, the difference between typical and atypical antipsychotics, the possible at-risk patient profile and the timing of stroke after exposure. A search of MEDLINE covering the period from 1966 to June 2009 was carried out using selected keywords. Inclusion criteria were (i) quantitative reviews on stroke and antipsychotics; (ii) double-blind, placebo-controlled clinical trials involving patients with dementia treated with antipsychotics; and (iii) observational database cohort studies and observational case-control studies investigating the association between stroke and antipsychotics. Clinical trials were excluded if they were single-blind or if patients were affected by dementia and/or other neurological illnesses. Four reviews with aggregate data, 2 meta-analyses, 13 randomized, double-blind, controlled trials, 7 observational cohort studies and 4 observational case-control studies were selected and analysed. The incidence of cerebrovascular accidents (CVAs) was found to be very low in aggregate reviews and meta-analyses (2-4%). When the number collected was sufficiently high, or different drug treatments were grouped together, the higher rate in subjects exposed to antipsychotics was statistically significant. Inspection of other randomized controlled clinical trials, not included in aggregate reviews and meta-analyses, reported similar rates of CVAs. The majority of observational cohort studies compared typical and atypical antipsychotics and no significant class differences were found. A comparison with non-users was carried out in some cohort studies. In case-control studies, the probability of CVAs in users compared with non-users was in the range of 1.3- to 2-fold greater. Preliminary data also indicate that the highest risk of stroke is related to the first weeks of treatment, and a risk profile for stroke is emerging, such as older age, cognitive impairment and vascular illness. Different pathophysiological pathways may be involved, ranging from the facilitation of thrombosis, pre-existing cardiovascular factors, sedation and a common diathesis for stroke of dementia, schizophrenia and affective illness. Before prescribing an antipsychotic, clinicians should weigh all the risk factors for a given patient and consider not only the indications as provided by the regulatory agencies, but also the overall effectiveness of typical and atypical antipsychotics.

Comparing U.S. Army suicide cases to a control sample: initial data and methodological lessons.

PubMed

Alexander, Cynthia L; Reger, Mark A; Smolenski, Derek J; Fullerton, Nicole R

2014-10-01

Identification of risk and protective factors for suicide is a priority for the United States military, especially in light of the recent steady increase in military suicide rates. The Department of Defense Suicide Event Report contains comprehensive data on suicides for active duty military personnel, but no analogous control data is available to permit identification of factors that differentially determine suicide risk. This proof-of-concept study was conducted to determine the feasibility of collecting such control data. The study employed a prospective case-control design in which control cases were randomly selected from a large Army installation at a rate of four control participants for every qualifying Army suicide. Although 111 Army suicides were confirmed during the study period, just 27 control soldiers completed the study. Despite the small control sample, preliminary analyses comparing suicide cases to controls identified several factors more frequently reported for suicide cases, including recent failed intimate relationships, outpatient mental health history, mood disorder diagnosis, substance abuse history, and prior self-injury. No deployment-related risk factors were found. These data are consistent with existing literature and form a foundation for larger control studies. Methodological lessons learned regarding study design and recruitment are discussed to inform future studies. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Genomic investigation of porcine periweaning failure to thrive syndrome (PFTS).

PubMed

Bertolini, Francesca; Yang, Tianfu; Huang, Yanyun; Harding, John C S; Plastow, Graham S; Rothschild, Max F

2018-04-25

Porcine periweaning failure to thrive syndrome (PFTS) can be defined by anorexia, lethargy, progressive debilitation and compulsive behaviours that occur in seemingly healthy pigs within two to threeweeks of weaning in the absence of any known infectious, nutritional, management or environmental factors. A genetic component has been hypothesised for this syndrome. In the present study, 119 commercial pigs (80 cases and 39 controls) were genotyped with the porcine 80K single nucleotide polymorphism-chip and were analysed with logistic regression and two Fixation Index-based approaches. The analyses revealed several regions on chromosomes 1, 3, 6 and 11 with moderate divergence between cases and controls, particularly three haplotypes on SSC3 and 11. The gene-based analyses of the candidate regions revealed the presence of genes that have been reported to be associated with phenotypes like PFST including depression ( PDE10A ) and intestinal villous atrophy ( CUL4A ). It is important to increase the effort of collecting more samples to improve the power of these analyses. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Sedentary work and the risk of breast cancer in premenopausal and postmenopausal women: a pooled analysis of two case-control studies.

PubMed

Boyle, Terry; Fritschi, Lin; Kobayashi, Lindsay C; Heyworth, Jane S; Lee, Derrick G; Si, Si; Aronson, Kristan J; Spinelli, John J

2016-11-01

There is limited research on the association between sedentary behaviour and breast cancer risk, particularly whether sedentary behaviour is differentially associated with premenopausal and postmenopausal breast cancer. We pooled data from 2 case-control studies from Australia and Canada to investigate this association. This pooled analysis included 1762 incident breast cancer cases and 2532 controls. Participants in both studies completed a lifetime occupational history and self-rated occupational physical activity level. A job-exposure matrix (JEM) was also applied to job titles to assess sedentary work. Logistic regression analyses (6 pooled and 12 study-specific) were conducted to estimate associations between both self-reported and JEM-assessed sedentary work and breast cancer risk among premenopausal and postmenopausal women. No association was observed in the 6 pooled analyses, and 10 of the study-specific analyses also showed null results. 2 study-specific analyses provided inconsistent and contradictory results, with 1 showing statistically significant increased risk of breast cancer for self-reported sedentary work among premenopausal women cancer in the Canadian study, and the other a non-significant inverse association between JEM-assessed sedentary work and breast cancer risk among postmenopausal women in the Australian study. While a suggestion of increased risk was seen for premenopausal women in the Canadian study when using the self-reported measure, overall this pooled study does not provide evidence that sedentary work is associated with breast cancer risk. 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/.

Genome-wide association analysis accounting for environmental factors through propensity-score matching: application to stressful live events in major depressive disorder.

PubMed

Power, Robert A; Cohen-Woods, Sarah; Ng, Mandy Y; Butler, Amy W; Craddock, Nick; Korszun, Ania; Jones, Lisa; Jones, Ian; Gill, Michael; Rice, John P; Maier, Wolfgang; Zobel, Astrid; Mors, Ole; Placentino, Anna; Rietschel, Marcella; Aitchison, Katherine J; Tozzi, Federica; Muglia, Pierandrea; Breen, Gerome; Farmer, Anne E; McGuffin, Peter; Lewis, Cathryn M; Uher, Rudolf

2013-09-01

Stressful life events are an established trigger for depression and may contribute to the heterogeneity within genome-wide association analyses. With depression cases showing an excess of exposure to stressful events compared to controls, there is difficulty in distinguishing between "true" cases and a "normal" response to a stressful environment. This potential contamination of cases, and that from genetically at risk controls that have not yet experienced environmental triggers for onset, may reduce the power of studies to detect causal variants. In the RADIANT sample of 3,690 European individuals, we used propensity score matching to pair cases and controls on exposure to stressful life events. In 805 case-control pairs matched on stressful life event, we tested the influence of 457,670 common genetic variants on the propensity to depression under comparable level of adversity with a sign test. While this analysis produced no significant findings after genome-wide correction for multiple testing, we outline a novel methodology and perspective for providing environmental context in genetic studies. We recommend contextualizing depression by incorporating environmental exposure into genome-wide analyses as a complementary approach to testing gene-environment interactions. Possible explanations for negative findings include a lack of statistical power due to small sample size and conditional effects, resulting from the low rate of adequate matching. Our findings underscore the importance of collecting information on environmental risk factors in studies of depression and other complex phenotypes, so that sufficient sample sizes are available to investigate their effect in genome-wide association analysis. Copyright © 2013 Wiley Periodicals, Inc.

Farm-level risk factors for Fasciola hepatica infection in Danish dairy cattle as evaluated by two diagnostic methods.

PubMed

Takeuchi-Storm, Nao; Denwood, Matthew; Hansen, Tina Vicky Alstrup; Halasa, Tariq; Rattenborg, Erik; Boes, Jaap; Enemark, Heidi Larsen; Thamsborg, Stig Milan

2017-11-09

The prevalence of bovine fasciolosis in Denmark is increasing but appropriate guidelines for control are currently lacking. In order to help develop a control strategy for liver fluke, a risk factor study of farm management factors was conducted and the utility of bulk tank milk (BTM ELISA) as a tool for diagnosis in Danish dairy cattle farms was assessed. This case-control study aimed to identify farm-level risk factors for fasciolosis in Danish dairy farms (> 50 animals slaughtered in 2013) using two diagnostic methods: recordings of liver condemnation at slaughter, and farm-level Fasciola hepatica antibody levels in BTM. A case farm was defined as having a minimum of 3 incidents of liver condemnation due to liver fluke at slaughter (in any age group) during 2013, and control farms were located within 10 km of at least one case farm and had no history of liver condemnation due to liver fluke during 2011-2013. The selected farmers were interviewed over telephone about grazing and control practices, and BTM from these farms was collected and analysed by ELISA in 2014. The final complete dataset consisting of 131 case and 63 control farms was analysed using logistic regression. Heifers grazing on wet pastures, dry cows grazing on wet pastures, herd size, breed and concurrent beef cattle production were identified as risk factors associated with being classified as a case farm. With the categorised BTM ELISA result as the response variable, heifers grazing on wet pastures, dry cows grazing on wet pastures, and purchase of cows were identified as risk factors. Within the case and control groups, 74.8 and 12.7% of farms were positive for fasciolosis on BTM ELISA, respectively. The differences are likely to be related to the detection limit of the farm-level prevalence by the BTM ELISA test, time span between slaughter data and BTM, and the relatively low sensitivity of liver inspection at slaughter. Control of bovine fasciolosis in Denmark should target heifers and dry cows through grazing management and appropriate anthelmintic treatment, and BTM ELISA can be a useful diagnostic tool for fasciolosis in Danish dairy farms.

Risk factors for unintentional poisoning in children aged 1-3 years in NSW Australia: a case-control study.

PubMed

Schmertmann, Marcia; Williamson, Ann; Black, Deborah; Wilson, Leigh

2013-05-24

Unintentional poisoning in young children is an important public health issue. Age pattern studies have demonstrated that children aged 1-3 years have the highest levels of poisoning risk among children aged 0-4 years, yet little research has been conducted regarding risk factors specific to this three-year age group and the methodologies employed varied greatly. The purpose of the current study is to investigate a broad range of potential risk factors for unintentional poisoning in children aged 1-3 years using appropriate methodologies. Four groups of children, one case group (children who had experienced a poisoning event) and three control groups (children who had been 'injured', 'sick' or who were 'healthy'), and their mothers (mother-child dyads) were enrolled into a case-control study. All mother-child dyads participated in a 1.5-hour child developmental screening and observation, with mothers responding to a series of questionnaires at home. Data were analysed as three case-control pairs with multivariate analyses used to control for age and sex differences between child cases and controls. Five risk factors were included in the final multivariate models for one or more case-control pairs. All three models found that children whose mothers used more positive control in their interactions during a structured task had higher odds of poisoning. Two models showed that maternal psychiatric distress increased poisoning risk (poisoning-injury and poisoning-healthy). Individual models identified the following variables as risk factors: less proximal maternal supervision during risk taking activities (poisoning-injury), medicinal substances stored in more accessible locations in bathrooms (poisoning-sick) and lower total parenting stress (poisoning-healthy). The findings of this study indicate that the nature of the caregiver-child relationship and caregiver attributes play an important role in influencing poisoning risk. Further research is warranted to explore the link between caregiver-child relationships and unintentional poisoning risk. Caregiver education should focus on the benefits of close interaction with their child as a prevention measure.

Selection bias due to differential participation in a case-control study of mobile phone use and brain tumors.

PubMed

Lahkola, Anna; Salminen, Tiina; Auvinen, Anssi

2005-05-01

To evaluate the possible selection bias related to the differential participation of mobile phone users and non-users in a Finnish case-control study on mobile phone use and brain tumors. Mobile phone use was investigated among 777 controls and 726 cases participating in the full personal interview (full participants), and 321 controls and 103 cases giving only a brief phone interview (incomplete participants). To assess selection bias, the Mantel-Haenszel estimate of odds ratio was calculated for three different groups: full study participants, incomplete participants, and a combined group consisting of both full and incomplete participants. Among controls, 83% of the full participants and 73% of the incomplete participants had regularly used a mobile phone. Among cases, the figures were 76% and 64%, respectively. The odds ratio for brain tumor based on the combined group of full and incomplete participants was slightly closer to unity than that based only on the full participants. Selection bias tends to distort the effect estimates below unity, while analyses based on more comprehensive material gave results close to unity.

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

PubMed

Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer's disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing.

Occupational exposure to pesticides and lymphoid neoplasms among men: results of a French case-control study

PubMed Central

Orsi, Laurent; Delabre, Laurene; Monnereau, Alain; Delval, Philippe; Berthou, Christian; Fenaux, Pierre; Marit, Gerald; Soubeyran, Pierre; Huguet, Francoise; Milpied, Noel; Leporrier, Michel; Hemon, Denis; Troussard, Xavier; Clavel, Jacqueline

2009-01-01

Objectives Investigating the relationship between occupational exposure to pesticides and the risk of lymphoid neoplasms (LN) in men. Methods A hospital-based case-control study was conducted in six centres in France between 2000 and 2004. The cases were incident cases with a diagnosis of lymphoid neoplasm aged 18 to 75 years. During the same period, controls of the same age and gender as the cases were recruited in the same hospital, mainly in the orthopaedic and rheumatological departments. Exposures to pesticides were evaluated through specific interviews and case-by-case expert reviews. Four hundred and ninety-one cases (244 cases of non-Hodgkin’s lymphoma (NHL), 87 of Hodgkin’s lymphoma (HL), 104 of lymphoproliferative syndromes (LPS) and 56 of multiple myeloma (MM) cases) and 456 controls were included in the analyses. The odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regressions. Results Positive associations between HL and occupational exposure to triazole fungicides and urea herbicides were observed (OR=8.4 [2.2–32.4], 10.8 [2.4–48.1] respectively). Exposure to insecticides, fungicides and herbicides were linked to a three-fold increases in MM risk (OR=2.8 [1.2–6.5], 3.2 [1.4–7.2], 2.9 [1.3–6.5]). For LPS subtypes, associations restricted to hairy-cell leukaemia (HCL) were evidenced for exposure to organochlorine insecticides, phenoxy herbicides and triazine herbicides (OR=4.9 [1.1–21.2], 4.1 [1.1–15.5], 5.1 [1.4–19.3]), although based on small numbers. Lastly, despite the increased odds ratios for organochlorine and organophosphate insecticides, carbamate fungicides and triazine herbicides, no significant associations were evidenced for NHL. Conclusions The results, based on case-by-case expert review of occupation-specific questionnaires, support the hypothesis that occupational pesticide exposures may be involved in HL, MM and HCL and do not rule out a role in NHL. The analyses identified specific pesticides that deserve further investigation and the findings were consistent with those of previous studies. PMID:19017688

Better cancer biomarker discovery through better study design.

PubMed

Rundle, Andrew; Ahsan, Habibul; Vineis, Paolo

2012-12-01

High-throughput laboratory technologies coupled with sophisticated bioinformatics algorithms have tremendous potential for discovering novel biomarkers, or profiles of biomarkers, that could serve as predictors of disease risk, response to treatment or prognosis. We discuss methodological issues in wedding high-throughput approaches for biomarker discovery with the case-control study designs typically used in biomarker discovery studies, especially focusing on nested case-control designs. We review principles for nested case-control study design in relation to biomarker discovery studies and describe how the efficiency of biomarker discovery can be effected by study design choices. We develop a simulated prostate cancer cohort data set and a series of biomarker discovery case-control studies nested within the cohort to illustrate how study design choices can influence biomarker discovery process. Common elements of nested case-control design, incidence density sampling and matching of controls to cases are not typically factored correctly into biomarker discovery analyses, inducing bias in the discovery process. We illustrate how incidence density sampling and matching of controls to cases reduce the apparent specificity of truly valid biomarkers 'discovered' in a nested case-control study. We also propose and demonstrate a new case-control matching protocol, we call 'antimatching', that improves the efficiency of biomarker discovery studies. For a valid, but as yet undiscovered, biomarker(s) disjunctions between correctly designed epidemiologic studies and the practice of biomarker discovery reduce the likelihood that true biomarker(s) will be discovered and increases the false-positive discovery rate. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

Hemifacial microsomia: from gestation to childhood.

PubMed

Werler, Martha M; Starr, Jacqueline R; Cloonan, Yona K; Speltz, Matthew L

2009-03-01

Hemifacial microsomia (HFM) is a variable, complex malformation involving asymmetric hypoplasia of the face and ear. Little is known about the risk factors for or consequences of HFM. In this study, we describe 3 studies that have been or are currently being conducted to further our understanding of this malformation. The first completed study examined whether HFM risk is related to maternal exposures that may affect blood flow. In that case-control study, interview data from 230 mothers of children in the case group and 678 mothers of children in the control group suggested that maternal use of vasoactive medications in the first trimester, particularly in combination with cigarette smoking, was associated with increased risks of HFM. The second study is currently underway, in which we are evaluating whether HFM risk is related to genetic variation in pathways associated with vasculogenesis and hemostasis, using DNA collected in the first study. The third ongoing study observes children with HFM to identify psychosocial, cognitive, dental, and medical sequelae. When the children from the original case-control study are 6 or 7 years of age, mothers and teachers complete self-administered questionnaires that cover a wide range of psychosocial development domains. Preliminary analyses of 115 case and 314 control children suggest that children with HFM may have worse teacher-reported academic performance and possibly higher levels of internalizing behavior problems than control children. When data on the full study sample are available, further analyses will determine whether the preliminary findings remain and if they vary by HFM phenotype, parenting style, or indicators of social risk.

Lack of association between the Trp719Arg polymorphism in kinesin-like protein 6 and coronary artery disease in 19 case-control studies

PubMed Central

Assimes, Themistocles L; Hólm, Hilma; Kathiresan, Sekar; Reilly, Muredach P; Thorleifsson, Gudmar; Voight, Benjamin F; Erdmann, Jeanette; Willenborg, Christina; Vaidya, Dhananjay; Xie, Changchun; Patterson, Chris C; Morgan, Thomas M; Burnett, Mary Susan; Li, Mingyao; Hlatky, Mark A; Knowles, Joshua W; Thompson, John R; Absher, Devin; Iribarren, Carlos; Go, Alan; Fortmann, Stephen P; Sidney, Stephen; Risch, Neil; Tang, Hua; Myers, Richard M; Berger, Klaus; Stoll, Monika; Shah, Svati H.; Thorgeirsson, Gudmundur; Andersen, Karl; Havulinna, Aki S; Herrera, J. Enrique; Faraday, Nauder; Kim, Yoonhee; Kral, Brian G.; Mathias, Rasika; Ruczinski, Ingo; Suktitipat, Bhoom; Wilson, Alexander F; Yanek, Lisa R.; Becker, Lewis C; Linsel-Nitschke, Patrick; Lieb, Wolfgang; König, Inke R; Hengstenberg, Christian; Fischer, Marcus; Stark, Klaus; Reinhard, Wibke; Winogradow, Janina; Grassl, Martina; Grosshennig, Anika; Preuss, Michael; Eifert, Sandra; Schreiber, Stefan; Wichmann, H-Erich; Meisinger, Christa; Yee, Jean; Friedlander, Yechiel; Do, Ron; Meigs, James B; Williams, Gordon; Nathan, David M; MacRae, Calum A; Qu, Liming; Wilensky, Robert L; Matthai, William H.; Qasim, Atif N; Hakonarson, Hakon; Pichard, Augusto D; Kent, Kenneth M; Satler, Lowell; Lindsay, Joseph M; Waksman, Ron; Knouff, Christopher W; Waterworth, Dawn M; Walker, Max C; Mooser, Vincent; Marrugat, Jaume; Lucas, Gavin; Subirana, Isaac; Sala, Joan; Ramos, Rafael; Martinelli, Nicola; Olivieri, Oliviero; Trabetti, Elisabetta; Malerba, Giovanni; Pignatti, Pier Franco; Guiducci, Candace; Mirel, Daniel; Parkin, Melissa; Hirschhorn, Joel N; Asselta, Rosanna; Duga, Stefano; Musunuru, Kiran; Daly, Mark J; Purcell, Shaun; Braund, Peter S; Wright, Benjamin J; Balmforth, Anthony J; Ball, Stephen G; Ouwehand, Willem H; Deloukas, Panos; Scholz, Michael; Cambien, Francois; Huge, Andreas; Scheffold, Thomas; Salomaa, Veikko; Girelli, Domenico; Granger, Christopher B.; Peltonen, Leena; McKeown, Pascal P; Altshuler, David; Melander, Olle; Devaney, Joseph M; Epstein, Stephen E; Rader, Daniel J; Elosua, Roberto; Engert, James C; Anand, Sonia S; Hall, Alistair S; Ziegler, Andreas; O’Donnell, Christopher J; Spertus, John A; Siscovick, David; Schwartz, Stephen M; Becker, Diane; Thorsteinsdottir, Unnur; Stefansson, Kari; Schunkert, Heribert; Samani, Nilesh J; Quertermous, Thomas

2011-01-01

Objectives We sought to replicate the association between the kinesin-like protein 6 (KIF6) Trp719Arg polymorphism (rs20455) and clinical coronary artery disease (CAD). Background Recent prospective studies suggest that carriers of the 719Arg allele in KIF6 are at increased risk of clinical CAD compared with non-carriers. Methods The KIF6 Trp719Arg polymorphism (rs20455) was genotyped in nineteen case-control studies of non-fatal CAD either as part of a genome-wide association study or in a formal attempt to replicate the initial positive reports. Results Over 17 000 cases and 39 000 controls of European descent as well as a modest number of South Asians, African Americans, Hispanics, East Asians, and admixed cases and controls were successfully genotyped. None of the nineteen studies demonstrated an increased risk of CAD in carriers of the 719Arg allele compared with non-carriers. Regression analyses and fixed effect meta-analyses ruled out with high degree of confidence an increase of ≥2% in the risk of CAD among European 719Arg carriers. We also observed no increase in the risk of CAD among 719Arg carriers in the subset of Europeans with early onset disease (<50 years of age for males and <60 years for females) compared with similarly aged controls as well as all non-European subgroups. Conclusions The KIF6 Trp719Arg polymorphism was not associated with the risk of clinical CAD in this large replication study. PMID:20933357

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions.

PubMed

Mamantopoulos, Michail; Ronchi, Francesca; McCoy, Kathy D; Wullaert, Andy

2018-04-19

Several human diseases are thought to evolve due to a combination of host genetic mutations and environmental factors that include alterations in intestinal microbiota composition termed dysbiosis. Although in some cases, host genetics may shape the gut microbiota and enable it to provoke disease, experimentally disentangling cause and consequence in such host-microbe interactions requires strict control over non-genetic confounding factors. Mouse genetic studies previously proposed Nlrp6/ASC inflammasomes as innate immunity regulators of the intestinal ecosystem. In contrast, using littermate-controlled experimental setups, we recently showed that Nlrp6/ASC inflammasomes do not alter the gut microbiota composition. Our analyses indicated that maternal inheritance and long-term separate housing are non-genetic confounders that preclude the use of non-littermate mice when analyzing host genetic effects on intestinal ecology. Here, we summarize and discuss our gut microbiota analyses in inflammasome-deficient mice for illustrating the importance of littermate experimental design in studying host-microbiota interactions.

Programs To Optimize Spacecraft And Aircraft Trajectories

NASA Technical Reports Server (NTRS)

Brauer, G. L.; Petersen, F. M.; Cornick, D.E.; Stevenson, R.; Olson, D. W.

1994-01-01

POST/6D POST is set of two computer programs providing ability to target and optimize trajectories of powered or unpowered spacecraft or aircraft operating at or near rotating planet. POST treats point-mass, three-degree-of-freedom case. 6D POST treats more-general rigid-body, six-degree-of-freedom (with point masses) case. Used to solve variety of performance, guidance, and flight-control problems for atmospheric and orbital vehicles. Applications include computation of performance or capability of vehicle in ascent, or orbit, and during entry into atmosphere, simulation and analysis of guidance and flight-control systems, dispersion-type analyses and analyses of loads, general-purpose six-degree-of-freedom simulation of controlled and uncontrolled vehicles, and validation of performance in six degrees of freedom. Written in FORTRAN 77 and C language. Two machine versions available: one for SUN-series computers running SunOS(TM) (LAR-14871) and one for Silicon Graphics IRIS computers running IRIX(TM) operating system (LAR-14869).

Quality of Diagnosis and Treatment Plans After Using the 'Diagnostic Guideline for Anxiety and Challenging Behaviours' in People with Intellectual Disabilities: A Comparative Multiple Case Study Design.

PubMed

Pruijssers, Addy; van Meijel, Berno; Maaskant, Marian; Keeman, Noortje; van Achterberg, Theo

2016-07-01

People with intellectual disabilities often have a multitude of concurrent problems due to the combination of cognitive impairments, psychiatric disorders (particularly anxiety) and related challenging behaviours. Diagnoses in people with intellectual disabilities are complicated. This study evaluates the quality of the diagnoses and treatment plans after using a guideline that was developed to support professionals in their diagnostic tasks. A comparative multiple case study with an experimental and control condition, applying deductive analyses of diagnoses and treatment plans. The analyses revealed that the number of diagnostic statements and planned treatment actions in the experimental group was significantly larger and more differentiated than in the control condition. In the control group, consequential harm and protective factors were hardly mentioned in diagnoses and treatment plans. Working with the 'Diagnostic Guideline for Anxiety and CB' leads to improved diagnoses and treatment plans compared with care as usual. © 2015 John Wiley & Sons Ltd.

A genome-wide association study in American Indians implicates DNER as a susceptibility locus for type 2 diabetes.

PubMed

Hanson, Robert L; Muller, Yunhua L; Kobes, Sayuko; Guo, Tingwei; Bian, Li; Ossowski, Victoria; Wiedrich, Kim; Sutherland, Jeffrey; Wiedrich, Christopher; Mahkee, Darin; Huang, Ke; Abdussamad, Maryam; Traurig, Michael; Weil, E Jennifer; Nelson, Robert G; Bennett, Peter H; Knowler, William C; Bogardus, Clifton; Baier, Leslie J

2014-01-01

Most genetic variants associated with type 2 diabetes mellitus (T2DM) have been identified through genome-wide association studies (GWASs) in Europeans. The current study reports a GWAS for young-onset T2DM in American Indians. Participants were selected from a longitudinal study conducted in Pima Indians and included 278 cases with diabetes with onset before 25 years of age, 295 nondiabetic controls ≥45 years of age, and 267 siblings of cases or controls. Individuals were genotyped on a ∼1M single nucleotide polymorphism (SNP) array, resulting in 453,654 SNPs with minor allele frequency >0.05. SNPs were analyzed for association in cases and controls, and a family-based association test was conducted. Tag SNPs (n = 311) were selected for 499 SNPs associated with diabetes (P < 0.0005 in case-control analyses or P < 0.0003 in family-based analyses), and these SNPs were genotyped in up to 6,834 additional Pima Indians to assess replication. Rs1861612 in DNER was associated with T2DM (odds ratio = 1.29 per copy of the T allele; P = 6.6 × 10(-8), which represents genome-wide significance accounting for the number of effectively independent SNPs analyzed). Transfection studies in murine pancreatic β-cells suggested that DNER regulates expression of notch signaling pathway genes. These studies implicate DNER as a susceptibility gene for T2DM in American Indians.

Phytoestrogen consumption from foods and supplements and epithelial ovarian cancer risk: a population-based case control study

PubMed Central

2011-01-01

Background While there is extensive literature evaluating the impact of phytoestrogen consumption on breast cancer risk, its role on ovarian cancer has received little attention. Methods We conducted a population-based case-control study to evaluate phytoestrogen intake from foods and supplements and epithelial ovarian cancer risk. Cases were identified in six counties in New Jersey through the New Jersey State Cancer Registry. Controls were identified by random digit dialing, CMS (Centers for Medicare and Medicaid Service) lists, and area sampling. A total of 205 cases and 390 controls were included in analyses. Unconditional logistic regression analyses were conducted to examine associations with total phytoestrogens, as well as isoflavones (daidzein, genistein, formononetin, and glycitein), lignans (matairesinol, lariciresinol, pinoresinol, secoisolariciresinol), and coumestrol. Results No statistically significant associations were found with any of the phytoestrogens under evaluation. However, there was a suggestion of an inverse association with total phytoestrogen consumption (from foods and supplements), with an odds ratio (OR) of 0.62 (95% CI: 0.38-1.00; p for trend: 0.04) for the highest vs. lowest tertile of consumption, after adjusting for reproductive covariates, age, race, education, BMI, and total energy. Further adjustment for smoking and physical activity attenuated risk estimates (OR: 0.66; 95% CI: 0.41-1.08). There was little evidence of an inverse association for isoflavones, lignans, or coumestrol. Conclusions This study provided some suggestion that phytoestrogen consumption may decrease ovarian cancer risk, although results did not reach statistical significance. PMID:21943063

Analysis of case-parent trios at a locus with a deletion allele: association of GSTM1 with autism.

PubMed

Buyske, Steven; Williams, Tanishia A; Mars, Audrey E; Stenroos, Edward S; Ming, Sue X; Wang, Rong; Sreenath, Madhura; Factura, Marivic F; Reddy, Chitra; Lambert, George H; Johnson, William G

2006-02-10

Certain loci on the human genome, such as glutathione S-transferase M1 (GSTM1), do not permit heterozygotes to be reliably determined by commonly used methods. Association of such a locus with a disease is therefore generally tested with a case-control design. When subjects have already been ascertained in a case-parent design however, the question arises as to whether the data can still be used to test disease association at such a locus. A likelihood ratio test was constructed that can be used with a case-parents design but has somewhat less power than a Pearson's chi-squared test that uses a case-control design. The test is illustrated on a novel dataset showing a genotype relative risk near 2 for the homozygous GSTM1 deletion genotype and autism. Although the case-control design will remain the mainstay for a locus with a deletion, the likelihood ratio test will be useful for such a locus analyzed as part of a larger case-parent study design. The likelihood ratio test has the advantage that it can incorporate complete and incomplete case-parent trios as well as independent cases and controls. Both analyses support (p = 0.046 for the proposed test, p = 0.028 for the case-control analysis) an association of the homozygous GSTM1 deletion genotype with autism.

Analysis of case-parent trios at a locus with a deletion allele: association of GSTM1 with autism

PubMed Central

Buyske, Steven; Williams, Tanishia A; Mars, Audrey E; Stenroos, Edward S; Ming, Sue X; Wang, Rong; Sreenath, Madhura; Factura, Marivic F; Reddy, Chitra; Lambert, George H; Johnson, William G

2006-01-01

Background Certain loci on the human genome, such as glutathione S-transferase M1 (GSTM1), do not permit heterozygotes to be reliably determined by commonly used methods. Association of such a locus with a disease is therefore generally tested with a case-control design. When subjects have already been ascertained in a case-parent design however, the question arises as to whether the data can still be used to test disease association at such a locus. Results A likelihood ratio test was constructed that can be used with a case-parents design but has somewhat less power than a Pearson's chi-squared test that uses a case-control design. The test is illustrated on a novel dataset showing a genotype relative risk near 2 for the homozygous GSTM1 deletion genotype and autism. Conclusion Although the case-control design will remain the mainstay for a locus with a deletion, the likelihood ratio test will be useful for such a locus analyzed as part of a larger case-parent study design. The likelihood ratio test has the advantage that it can incorporate complete and incomplete case-parent trios as well as independent cases and controls. Both analyses support (p = 0.046 for the proposed test, p = 0.028 for the case-control analysis) an association of the homozygous GSTM1 deletion genotype with autism. PMID:16472391

Integrated analyses for genetic markers of polycystic ovary syndrome with 9 case-control studies of gene expression profiles.

PubMed

Lu, Chenqi; Liu, Xiaoqin; Wang, Lin; Jiang, Ning; Yu, Jun; Zhao, Xiaobo; Hu, Hairong; Zheng, Saihua; Li, Xuelian; Wang, Guiying

2017-01-10

Due to genetic heterogeneity and variable diagnostic criteria, genetic studies of polycystic ovary syndrome are particularly challenging. Furthermore, lack of sufficiently large cohorts limits the identification of susceptibility genes contributing to polycystic ovary syndrome. Here, we carried out a systematic search of studies deposited in the Gene Expression Omnibus database through August 31, 2016. The present analyses included studies with: 1) patients with polycystic ovary syndrome and normal controls, 2) gene expression profiling of messenger RNA, and 3) sufficient data for our analysis. Ultimately, a total of 9 studies with 13 datasets met the inclusion criteria and were performed for the subsequent integrated analyses. Through comprehensive analyses, there were 13 genetic factors overlapped in all datasets and identified as significant specific genes for polycystic ovary syndrome. After quality control assessment, there were six datasets remained. Further gene ontology enrichment and pathway analyses suggested that differentially expressed genes mainly enriched in oocyte pathways. These findings provide potential molecular markers for diagnosis and prognosis of polycystic ovary syndrome, and need in-depth studies on the exact function and mechanism in polycystic ovary syndrome.

PAI-1 -675 4G/5G Polymorphism in Association with Diabetes and Diabetic Complications Susceptibility: a Meta-Analysis Study

PubMed Central

Yang, Fan; Cui, Dai; Shi, Yun; Shen, Chong; Tang, Wei; Yang, Tao

2013-01-01

A meta-analysis was performed to assess the association between the PAI-1 -675 4G/5G polymorphism and susceptibility to diabetes mellitus (DM), diabetic nephropathy (DN), diabetic retinopathy (DR) and diabetic coronary artery disease (CAD). A literature-based search was conducted to identify all relevant studies. The fixed or random effect pooled measure was calculated mainly at the allele level to determine heterogeneity bias among studies. Further stratified analyses and sensitivity analyses were also performed. Publication bias was examined by the modified Begg’s and Egger’s test. Twenty published articles with twenty-seven outcomes were included in the meta-analysis: 6 studies with a total of 1,333 cases and 3,011 controls were analyzed for the PAI-1 -675 4G/5G polymorphism with diabetes risk, 7 studies with 1,060 cases and 1,139 controls for DN risk, 10 studies with 1,327 cases and 1,557 controls for DR and 4 studies with 610 cases and 1,042 controls for diabetic CAD risk respectively. Using allelic comparison (4G vs. 5G), the PAI-1 -675 4G/5G polymorphism was observed to have no significant association with diabetes (REM OR 1.07, 95% CI 0.96, 1.20), DN (REM OR 1.10, 95% CI 0.98, 1.25), DR (REM OR 1.09, 95% CI 0.97, 1.22) or diabetic CAD risk (REM OR 1.07, 95% CI 0.81, 1.42), and similar results were obtained in the dominant, recessive and co-dominant models. Our meta-analyses suggest that the PAI-1 -675 4G/5G polymorphism might not be a risk factor for DM, DN, DR or diabetic CAD risk in the populations investigated. This conclusion warrants confirmation by further studies. PMID:24223897

PAI-1 -675 4G/5G polymorphism in association with diabetes and diabetic complications susceptibility: a meta-analysis study.

PubMed

Xu, Kuanfeng; Liu, Xiaoyun; Yang, Fan; Cui, Dai; Shi, Yun; Shen, Chong; Tang, Wei; Yang, Tao

2013-01-01

A meta-analysis was performed to assess the association between the PAI-1 -675 4G/5G polymorphism and susceptibility to diabetes mellitus (DM), diabetic nephropathy (DN), diabetic retinopathy (DR) and diabetic coronary artery disease (CAD). A literature-based search was conducted to identify all relevant studies. The fixed or random effect pooled measure was calculated mainly at the allele level to determine heterogeneity bias among studies. Further stratified analyses and sensitivity analyses were also performed. Publication bias was examined by the modified Begg's and Egger's test. Twenty published articles with twenty-seven outcomes were included in the meta-analysis: 6 studies with a total of 1,333 cases and 3,011 controls were analyzed for the PAI-1 -675 4G/5G polymorphism with diabetes risk, 7 studies with 1,060 cases and 1,139 controls for DN risk, 10 studies with 1,327 cases and 1,557 controls for DR and 4 studies with 610 cases and 1,042 controls for diabetic CAD risk respectively. Using allelic comparison (4G vs. 5G), the PAI-1 -675 4G/5G polymorphism was observed to have no significant association with diabetes (REM OR 1.07, 95% CI 0.96, 1.20), DN (REM OR 1.10, 95% CI 0.98, 1.25), DR (REM OR 1.09, 95% CI 0.97, 1.22) or diabetic CAD risk (REM OR 1.07, 95% CI 0.81, 1.42), and similar results were obtained in the dominant, recessive and co-dominant models. Our meta-analyses suggest that the PAI-1 -675 4G/5G polymorphism might not be a risk factor for DM, DN, DR or diabetic CAD risk in the populations investigated. This conclusion warrants confirmation by further studies.

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.

Cooperative Genome-Wide Analysis Shows Increased Homozygosity in Early Onset Parkinson's Disease

PubMed Central

Nalls, Michael A.; Martinez, Maria; Schulte, Claudia; Holmans, Peter; Gasser, Thomas; Hardy, John; Singleton, Andrew B.; Wood, Nicholas W.; Brice, Alexis; Heutink, Peter; Williams, Nigel; Morris, Huw R.

2012-01-01

Parkinson's disease (PD) occurs in both familial and sporadic forms, and both monogenic and complex genetic factors have been identified. Early onset PD (EOPD) is particularly associated with autosomal recessive (AR) mutations, and three genes, PARK2, PARK7 and PINK1, have been found to carry mutations leading to AR disease. Since mutations in these genes account for less than 10% of EOPD patients, we hypothesized that further recessive genetic factors are involved in this disorder, which may appear in extended runs of homozygosity. We carried out genome wide SNP genotyping to look for extended runs of homozygosity (ROHs) in 1,445 EOPD cases and 6,987 controls. Logistic regression analyses showed an increased level of genomic homozygosity in EOPD cases compared to controls. These differences are larger for ROH of 9 Mb and above, where there is a more than three-fold increase in the proportion of cases carrying a ROH. These differences are not explained by occult recessive mutations at existing loci. Controlling for genome wide homozygosity in logistic regression analyses increased the differences between cases and controls, indicating that in EOPD cases ROHs do not simply relate to genome wide measures of inbreeding. Homozygosity at a locus on chromosome19p13.3 was identified as being more common in EOPD cases as compared to controls. Sequencing analysis of genes and predicted transcripts within this locus failed to identify a novel mutation causing EOPD in our cohort. There is an increased rate of genome wide homozygosity in EOPD, as measured by an increase in ROHs. These ROHs are a signature of inbreeding and do not necessarily harbour disease-causing genetic variants. Although there might be other regions of interest apart from chromosome 19p13.3, we lack the power to detect them with this analysis. PMID:22427796

Genetic characterization of Shigella spp. isolated from diarrhoeal and asymptomatic children.

PubMed

Ghosh, Santanu; Pazhani, Gururaja P; Niyogi, Swapan Kumar; Nataro, James P; Ramamurthy, Thandavarayan

2014-07-01

Phenotypic and genetic characteristics of Shigella spp. isolated from diarrhoeal and asymptomatic children aged up to 5 years were analysed in this study. In total, 91 and 17 isolates were identified from diarrhoeal (case) and asymptomatic (control) children, respectively. All the isolates were tested for antimicrobial resistance, the presence of integrons, plasmid-mediated quinolone resistance (PMQR), virulence-associated genes and Shigella pathogenicity island (SH-PAI). The majority of the Shigella spp. from cases (68.1%) and controls (82.3%) were found to be resistant to fluoroquinolones. Integron carriage was detected more in cases (76.9%) than in controls (35.5%). Atypical class 1 integron was detected exclusively in Shigella flexneri from cases but not from the controls. PMQR genes such as aac(6')-Ib-cr and qnrS1 were detected in 82.4 and 14.3% of the isolates from cases and in 53 and 17.6% in controls, respectively. Shigella isolates from cases as well as from controls were positive for the invasive plasmid antigen H-encoding gene ipaH. The other virulence genes such as virF, sat, setA, setB, sen and ial were detected in Shigella isolates in 80.2, 49.4, 27.4, 27.4, 80.2 and 79.1% of cases and in 64.7, 52.9, 17.6, 17.6, 64.7 and 64.7% of controls, respectively. The entire SH-PAI was detected in S. flexneri serotype 2a from cases and controls. In an isolate from a control child, the SH-PAI was truncated. Integrons, PMQR and virulence-encoding genes were detected more frequently in cases than in controls. In diarrhoea endemic areas, asymptomatic carriers may play a crucial role in the transmission of multidrug-resistant Shigella spp. with all the putative virulence genes. © 2014 The Authors.

Subcortical brain volume differences of participants with ADHD across the lifespan: an ENIGMA collaboration

PubMed Central

Hoogman, Martine; Bralten, Janita; Hibar, Derrek P.; Mennes, Maarten; Zwiers, Marcel P.; Schweren, Lizanne; van Hulzen, Kimm J.E.; Medland, Sarah E.; Shumskaya, Elena; Jahanshad, Neda; de Zeeuw, Patrick; Szekely, Eszter; Sudre, Gustavo; Wolfers, Thomas; Onnink, Alberdingk M.H.; Dammers, Janneke T.; Mostert, Jeanette C.; Vives-Gilabert, Yolanda; Kohls, Gregor; Oberwelland, Eileen; Seitz, Jochen; Schulte-Rüther, Martin; di Bruttopilo, Sara Ambrosino; Doyle, Alysa E.; Høvik, Marie F.; Dramsdahl, Margaretha; Tamm, Leanne; van Erp, Theo G.M.; Dale, Anders; Schork, Andrew; Conzelmann, Annette; Zierhut, Kathrin; Baur, Ramona; McCarthy, Hazel; Yoncheva, Yuliya N.; Cubillo, Ana; Chantiluke, Kaylita; Mehta, Mitul A.; Paloyelis, Yannis; Hohmann, Sarah; Baumeister, Sarah; Bramati, Ivanei; Mattos, Paulo; Tovar-Moll, Fernanda; Douglas, Pamela; Banaschewski, Tobias; Brandeis, Daniel; Kuntsi, Jonna; Asherson, Phil; Rubia, Katya; Kelly, Clare; Di Martino, Adriana; Milham, Michael P.; Castellanos, Francisco X.; Frodl, Thomas; Zentis, Mariam; Lesch, Klaus-Peter; Reif, Andreas; Pauli, Paul; Jernigan, Terry; Haavik, Jan; Plessen, Kerstin J.; Lundervold, Astri J.; Hugdahl, Kenneth; Seidman, Larry J.; Biederman, Joseph; Rommelse, Nanda; Heslenfeld, Dirk J.; Hartman, Catharina; Hoekstra, Pieter J.; Oosterlaan, Jaap; von Polier, Georg; Konrad, Kerstin; Vilarroya, Oscar; Ramos-Quiroga, Josep-Antoni; Soliva, Joan Carles; Durston, Sarah; Buitelaar, Jan K.; Faraone, Stephen V.; Shaw, Philip; Thompson, Paul; Franke, Barbara

2017-01-01

BACKGROUND Neuroimaging studies show structural alterations in several brain regions in children and adults with attention-deficit/hyperactivity disorder (ADHD). Through the formation of the worldwide ENIGMA ADHD Working Group, we addressed weaknesses of prior imaging studies and meta-analyses in sample size and methodological heterogeneity. METHODS Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites (age range: 4–63 years; 66% males). Individual sites analyzed magnetic resonance imaging brain scans with harmonized protocols. Case-control differences in subcortical structures and intracranial volume (ICV) were assessed through mega-and meta-analysis. FINDINGS The volumes of the accumbens (Cohen’s d=−0.15), amygdala (d=−0.19), caudate (d=−0.11), hippocampus (d=−0.11), putamen (d=−0.14), and ICV (d=−0.10) were found to be smaller in cases relative to controls. Effect sizes were highest in children, case-control differences were not present in adults. Explorative lifespan modeling suggested a delay of maturation and a delay of degeneration. Psychostimulant medication use or presence of comorbid psychiatric disorders did not influence results, nor did symptom scores correlate with brain volume. INTERPRETATION Using the largest data set to date, we extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. We add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD, and provide unprecedented precision in effect size estimates. Lifespan analyses suggest that, in the absence of well-powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of life provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. FUNDING National Institutes of Health PMID:28219628

Does physical activity moderate the relationship between depression symptomatology and low back pain? Cohort and co-twin control analyses nested in the longitudinal study of aging Danish twins (LSADT).

PubMed

Hübscher, Markus; Hartvigsen, Jan; Fernandez, Matthew; Christensen, Kaare; Ferreira, Paulo

2016-04-01

To investigate whether depression symptomatology is associated with low back pain (LBP) in twins aged 70+ and whether this effect depends on a person's physical activity (PA) status. This prospective cohort and nested case-control study used a nationally representative sample of twins. Data on depression symptomatology (modified Cambridge Mental Disorders Examination) and self-reported PA were obtained from the Longitudinal Study of Aging Danish Twins using twins without LBP at baseline. Associations between depression symptomatology (highest quartile) at baseline and LBP two years later were investigated using logistic regression analyses adjusted for sex. To examine the moderating effect of PA, we tested its interaction with depression. Associations were analysed using the complete sample of 2446 twins and a matched case-control analysis of 97 twin pairs discordant for LBP at follow-up. Odds ratios (OR) with 95% confidence intervals (CI) were calculated. Using the whole sample, high depression scores were associated with an increased probability of LBP (OR 1.56, 95% CI 1.22-1.99, P ≤ 0.01). There was no statistically significant interaction of light PA and depression symptomatology (OR 0.78, 95% CI 0.46-1.35, P = 0.39) and strenuous PA and depression symptomatology (0.84, 95% CI 0.50-1.41, P = 0.51). The case-control analysis showed similar ORs, although statistically insignificant. High depression symptomatology predicted incident LBP. This effect is supposedly not attributable to genetic or shared environmental factors. Physical activity did not moderate the effect of depression symptomatology on LBP.

What factors play a role in preventing self-immolation? Results from a case-control study in Iran

PubMed Central

Karim, Hosein; Schwebel, David C.; Bazargan-Hejazi, Shahrzad; Mohammadi, Reza; Choubsaz, Mansour; Heidari Zadie, Zahra; Ahmadi, Alireza

2015-01-01

Abstract: Background: To investigate factors related to prevention of self-immolation in west of Iran. Methods: In a case-control study, 30 consecutive cases of deliberate self-inflicted burns admitted to the regional burn center (Imam Khomeini hospital in Kermanshah province, Iran) were compared with controls selected from the community and matched by sex, age, district-county of residence, and rural vs urban living environment. The following characteristics relevant to preventing self-immolation were collected from all cases and controls: main domestic fuel used in the household, awareness about complications of burn injuries, and use of counseling services. Results: Descriptive analyses revealed that kerosene was the main domestic fuel in the household for 83% of cases. Not surprisingly, the main means of self-immolation in 93% of the patients was kerosene, with other fuels such as petrol and domestic gas used in remaining cases. The majority of cases and controls were aware of the potential complications of burn injuries. Use of counseling services was more common in controls. Conclusions: All three aspects of preventing self-immolation – having kerosene and other fuels in the home, being aware of the complications of burn injuries, and using counseling services were present in both the cases and controls. This suggests a large portion of residents in rural Iran are potential self-immolation victims. Increasing preventive strategies may reduce risk of suicide by self-immolation. PMID:26081518

Decreased hospital length of stay associated with presentation of cases at morning report with librarian support

PubMed Central

Banks, Daniel E.; Shi, Runhua; Timm, Donna F.; Christopher, Kerri Ann; Duggar, David Charles; Comegys, Marianne; McLarty, Jerry

2007-01-01

Objective: The research sought to determine whether case discussion at residents' morning report (MR), accompanied by a computerized literature search and librarian support, affects hospital charges, length of stay (LOS), and thirty-day readmission rate. Methods: This case-control study, conducted from August 2004 to March 2005, compared outcomes for 105 cases presented at MR within 24 hours of admission to 19,210 potential matches, including cases presented at MR and cases not presented at MR. With matching criteria of patient age (± 5 years), identical primary diagnosis, and secondary diagnoses (within 3 additional diagnoses) using International Classification of Diseases (ICD-9) codes, 55 cases were matched to 136 controls. Statistical analyses included Student's t tests, chi-squared tests, and nonparametric methods. Results: LOS differed significantly between matched MR cases and controls (3 days vs. 5 days, P < 0.024). Median total hospital charges were $7,045 for the MR group and $10,663 for the control group. There was no difference in 30-day readmission rate between the 2 groups. Discussion/Conclusion: Presentation of a case at MR, followed by the timely dissemination of the results of an online literature review, resulted in a shortened LOS and lower hospital charges compared with controls. MR, in association with a computerized literature search guided by the librarians, was an effective means for introducing evidence-based medicine into patient care practices. PMID:17971885

A program for mass spectrometer control and data processing analyses in isotope geology; written in BASIC for an 8K Nova 1120 computer

USGS Publications Warehouse

Stacey, J.S.; Hope, J.

1975-01-01

A system is described which uses a minicomputer to control a surface ionization mass spectrometer in the peak switching mode, with the object of computing isotopic abundance ratios of elements of geologic interest. The program uses the BASIC language and is sufficiently flexible to be used for multiblock analyses of any spectrum containing from two to five peaks. In the case of strontium analyses, ratios are corrected for rubidium content and normalized for mass spectrometer fractionation. Although almost any minicomputer would be suitable, the model used was the Data General Nova 1210 with 8K memory. Assembly language driver program and interface hardware-descriptions for the Nova 1210 are included.

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.

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.

Massive outbreak of viral gastroenteritis associated with consumption of municipal drinking water in a European capital city.

PubMed

Werber, D; Lausević, D; Mugosa, B; Vratnica, Z; Ivanović-Nikolić, L; Zizić, L; Alexandre-Bird, A; Fiore, L; Ruggeri, F M; Di Bartolo, I; Battistone, A; Gassilloud, B; Perelle, S; Nitzan Kaluski, D; Kivi, M; Andraghetti, R; Pollock, K G J

2009-12-01

On 24 August 2008, an outbreak alert regarding cases of acute gastroenteritis in Podgorica triggered investigations to guide control measures. From 23 August to 7 September, 1699 cases were reported in Podgorica (population 136 000) and we estimated the total size of the outbreak to be 10 000-15 000 corresponding to an attack rate of approximately 10%. We conducted an age- and neighbourhood-matched case-control study, microbiologically analysed faecal and municipal water samples and assessed the water distribution system. All cases (83/83) and 90% (80/90) [corrected] of controls drank unboiled chlorinated municipal water [matched odds ratio (mOR) 11.2, 95% confidence interval (CI), 1.6-infinity]. Consumption of bottled water was inversely associated with illness (mOR 0.3, 95% CI 0.1-0.8). Analyses of faecal samples identified six norovirus genotypes (21/38 samples) and occasionally other viruses. Multiple defects in the water distribution system were noted. These results suggest that the outbreak was caused by faecally contaminated municipal water. It is unusual to have such a large outbreak in a European city especially when the municipal water supply is chlorinated. Therefore, it is important to establish effective multiple-barrier water-treatment systems whenever possible, but even with an established chlorinated supply, sustained vigilance is central to public health.

Rare copy number variants in patients with congenital conotruncal heart defects.

PubMed

Xie, Hongbo M; Werner, Petra; Stambolian, Dwight; Bailey-Wilson, Joan E; Hakonarson, Hakon; White, Peter S; Taylor, Deanne M; Goldmuntz, Elizabeth

2017-03-01

Previous studies using different cardiac phenotypes, technologies and designs suggest a burden of large, rare or de novo copy number variants (CNVs) in subjects with congenital heart defects. We sought to identify disease-related CNVs, candidate genes, and functional pathways in a large number of cases with conotruncal and related defects that carried no known genetic syndrome. Cases and control samples were divided into two cohorts and genotyped to assess each subject's CNV content. Analyses were performed to ascertain differences in overall CNV prevalence and to identify enrichment of specific genes and functional pathways in conotruncal cases relative to healthy controls. Only findings present in both cohorts are presented. From 973 total conotruncal cases, a burden of rare CNVs was detected in both cohorts. Candidate genes from rare CNVs found in both cohorts were identified based on their association with cardiac development or disease, and/or their reported disruption in published studies. Functional and pathway analyses revealed significant enrichment of terms involved in either heart or early embryonic development. Our study tested one of the largest cohorts specifically with cardiac conotruncal and related defects. These results confirm and extend previous findings that CNVs contribute to disease risk for congenital heart defects in general and conotruncal defects in particular. As disease heterogeneity renders identification of single recurrent genes or loci difficult, functional pathway and gene regulation network analyses appear to be more informative. Birth Defects Research 109:271-295, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The impact of the Catholic Jubilee in 2000 on infectious diseases. A case-control study of giardiasis, Rome, Italy 2000-2001.

PubMed

Faustini, A; Marinacci, C; Fabrizi, E; Marangi, M; Recchia, O; Pica, R; Giustini, F; La Marca, A; Nacci, A; Panichi, G; Perucci, C A

2006-06-01

Mass gatherings are believed to increase the transmission of infectious diseases although surveillance systems have shown a low impact. The Catholic Jubilee was held in Rome, Italy in 2000. We conducted a case-control study to analyse the risk factors of giardiasis among residents. All diseases reported to the laboratory surveillance system from January 2000 to May 2001 were compared with hospital controls concurrently selected in the same season as cases and frequency-matched for age and birth country. Fifty-two cases (44.1%) and 72 controls were enrolled. In the multivariable analysis factors associated with giardiasis among adults were: travelling abroad (OR 24.2, P>0.01), exposure to surface water (OR 4.80, P=0.05), high educational level (OR 3.8, P=0.03). Having a maid from a high-prevalence country was independently associated (OR 2.3) although not statistically significant. This is the only exposure that changed during the Jubilee.

The Impact of Baseline Trend Control on Visual Analysis of Single-Case Data

ERIC Educational Resources Information Center

Mercer, Sterett H.; Sterling, Heather E.

2012-01-01

The impact of baseline trend control on visual analyses of AB intervention graphs was examined with simulated data at various values of baseline trend, autocorrelation, and effect size. Participants included 202 undergraduate students with minimal training in visual analysis and 10 graduate students and faculty with more training and experience in…

Unconditional analyses can increase efficiency in assessing gene-environment interaction of the case-combined-control design.

PubMed

Goldstein, Alisa M; Dondon, Marie-Gabrielle; Andrieu, Nadine

2006-08-01

A design combining both related and unrelated controls, named the case-combined-control design, was recently proposed to increase the power for detecting gene-environment (GxE) interaction. Under a conditional analytic approach, the case-combined-control design appeared to be more efficient and feasible than a classical case-control study for detecting interaction involving rare events. We now propose an unconditional analytic strategy to further increase the power for detecting gene-environment (GxE) interactions. This strategy allows the estimation of GxE interaction and exposure (E) main effects under certain assumptions (e.g. no correlation in E between siblings and the same exposure frequency in both control groups). Only the genetic (G) main effect cannot be estimated because it is biased. Using simulations, we show that unconditional logistic regression analysis is often more efficient than conditional analysis for detecting GxE interaction, particularly for a rare gene and strong effects. The unconditional analysis is also at least as efficient as the conditional analysis when the gene is common and the main and joint effects of E and G are small. Under the required assumptions, the unconditional analysis retains more information than does the conditional analysis for which only discordant case-control pairs are informative leading to more precise estimates of the odds ratios.

Thyrotropin receptor autoantibodies and early miscarriages in patients with Hashimoto thyroiditis: a case-control study.

PubMed

Toulis, Konstantinos A; Goulis, Dimitrios G; Tsolakidou, Konstantina; Hilidis, Ilias; Fragkos, Marios; Polyzos, Stergios A; Gerofotis, Antonios; Kita, Marina; Bili, Helen; Vavilis, Dimitrios; Daniilidis, Michail; Tarlatzis, Basil C; Papadimas, Ioannis

2013-08-01

We have previously hypothesized that early miscarriage in women with Hashimoto thyroiditis might be the result of a cross-reactivity process, in which blocking autoantibodies against thyrotropin receptor (TSHr-Ab) antagonize hCG action on its receptor on the corpus luteum. To test this hypothesis from the clinical perspective, we investigated the presence of TSHr-Ab in Hashimoto thyroiditis patients with apparently unexplained, first-trimester recurrent miscarriages compared to that in Hashimoto thyroiditis patients with documented normal fertility. A total of 86 subjects (43 cases and 43 age-matched controls) were finally included in a case-control study. No difference in the prevalence of TSHr-Ab positivity was detected between cases and controls (Fisher's exact test, p value = 1.00). In patients with recurrent miscarriages, TSHr-Ab concentrations did not predict the number of miscarriages (univariate linear regression, p value = 0.08). These results were robust in sensitivity analyses, including only cases with full investigation or those with three or more miscarriages. We conclude that no role could be advocated for TSHr-Ab in the aetiology of recurrent miscarriages in women with Hashimoto thyroiditis.

Night shift work and breast cancer risk: what do the meta-analyses tell us?

PubMed

Pahwa, Manisha; Labrèche, France; Demers, Paul A

2018-05-22

Objectives This paper aims to compare results, assess the quality, and discuss the implications of recently published meta-analyses of night shift work and breast cancer risk. Methods A comprehensive search was conducted for meta-analyses published from 2007-2017 that included at least one pooled effect size (ES) for breast cancer associated with any night shift work exposure metric and were accompanied by a systematic literature review. Pooled ES from each meta-analysis were ascertained with a focus on ever/never exposure associations. Assessments of heterogeneity and publication bias were also extracted. The AMSTAR 2 checklist was used to evaluate quality. Results Seven meta-analyses, published from 2013-2016, collectively included 30 cohort and case-control studies spanning 1996-2016. Five meta-analyses reported pooled ES for ever/never night shift work exposure; these ranged from 0.99 [95% confidence interval (CI) 0.95-1.03, N=10 cohort studies) to 1.40 (95% CI 1.13-1.73, N=9 high quality studies). Estimates for duration, frequency, and cumulative night shift work exposure were scant and mostly not statistically significant. Meta-analyses of cohort, Asian, and more fully-adjusted studies generally resulted in lower pooled ES than case-control, European, American, or minimally-adjusted studies. Most reported statistically significant between-study heterogeneity. Publication bias was not evident in any of the meta-analyses. Only one meta-analysis was strong in critical quality domains. Conclusions Fairly consistent elevated pooled ES were found for ever/never night shift work and breast cancer risk, but results for other shift work exposure metrics were inconclusive. Future evaluations of shift work should incorporate high quality meta-analyses that better appraise individual study quality.

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.

Informing the Symptom Profile of Complicated Grief

PubMed Central

Simon, Naomi M.; Wall, Melanie M.; Keshaviah, Aparna; Dryman, M. Taylor; LeBlanc, Nicole J.; Shear, M. Katherine

2010-01-01

Background Complicated Grief (CG) is under consideration as a new diagnosis in DSM5. We sought to add empirical support to the current dialogue by examining the commonly used Inventory of Complicated Grief (ICG) scale completed by 782 bereaved individuals. Methods We employed IRT analyses, factor analyses, and sensitivity and specificity analyses utilizing our full sample (n=782), and also compared confirmed CG cases (n=288) to non-cases (n=377). Confirmed CG cases were defined as individuals bereaved at least 6 months who were seeking care for CG, had an ICG ≥ 30, and received a structured clinical interview for CG by a certified clinician confirming CG as their primary illness. Non-cases were bereaved individuals who did not present with CG as a primary complaint (including those with depression, bipolar disorder, anxiety disorders and controls) and had an ICG<25. Results IRT analyses provided guidance about the most informative individual items and their association with CG severity. Factor analyses demonstrated a single factor solution when the full sample was considered, but within CG cases, six symptom clusters emerged: 1) yearning and preoccupation with the deceased, 2) anger and bitterness, 3) shock and disbelief, 4) estrangement from others, 5) hallucinations of the deceased, and 6) behavior change, including avoidance and proximity seeking. The presence of at least one symptom from three different symptom clusters optimized sensitivity (94.8%) and specificity (98.1%). Conclusions These data, derived from a diverse and predominantly clinical help seeking population, add an important perspective to existing suggestions for DSM5 criteria for CG. PMID:21284064

Continuing difficulties in interpreting CNV data: lessons from a genome-wide CNV association study of Australian HNPCC/lynch syndrome patients

PubMed Central

2013-01-01

Background Hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome (LS) is a cancer syndrome characterised by early-onset epithelial cancers, especially colorectal cancer (CRC) and endometrial cancer. The aim of the current study was to use SNP-array technology to identify genomic aberrations which could contribute to the increased risk of cancer in HNPCC/LS patients. Methods Individuals diagnosed with HNPCC/LS (100) and healthy controls (384) were genotyped using the Illumina Human610-Quad SNP-arrays. Copy number variation (CNV) calling and association analyses were performed using Nexus software, with significant results validated using QuantiSNP. TaqMan Copy-Number assays were used for verification of CNVs showing significant association with HNPCC/LS identified by both software programs. Results We detected copy number (CN) gains associated with HNPCC/LS status on chromosome 7q11.21 (28% cases and 0% controls, Nexus; p = 3.60E-20 and QuantiSNP; p < 1.00E-16) and 16p11.2 (46% in cases, while a CN loss was observed in 23% of controls, Nexus; p = 4.93E-21 and QuantiSNP; p = 5.00E-06) via in silico analyses. TaqMan Copy-Number assay was used for validation of CNVs showing significant association with HNPCC/LS. In addition, CNV burden (total CNV length, average CNV length and number of observed CNV events) was significantly greater in cases compared to controls. Conclusion A greater CNV burden was identified in HNPCC/LS cases compared to controls supporting the notion of higher genomic instability in these patients. One intergenic locus on chromosome 7q11.21 is possibly associated with HNPCC/LS and deserves further investigation. The results from this study highlight the complexities of fluorescent based CNV analyses. The inefficiency of both CNV detection methods to reproducibly detect observed CNVs demonstrates the need for sequence data to be considered alongside intensity data to avoid false positive results. PMID:23531357

The remote controlling technique based on the serial port for SR-620 universal counter

NASA Astrophysics Data System (ADS)

Su, Jian-Feng; Chen, Shu-Fang; Li, Xiao-Hui; Wu, Hai-Tao; Bian, Yu-Jing

2004-12-01

The function of SR-620 universal counter and the remote work mode are introduced, and the remote controlling technique for the counter is analysed. A method to realize the remote controlling via the serial port for the counter is demonstrated, in which an ActiveX control is used. Besides, some points for attention in debugging are discussed based on the experience, and a case of program running for measuring time-delay is presented.

Adaptation of Cost Analysis Studies in Practice Guidelines.

PubMed

Zervou, Fainareti N; Zacharioudakis, Ioannis M; Pliakos, Elina Eleftheria; Grigoras, Christos A; Ziakas, Panayiotis D; Mylonakis, Eleftherios

2015-12-01

Clinical guidelines play a central role in day-to-day practice. We assessed the degree of incorporation of cost analyses to guidelines and identified modifiable characteristics that could affect the level of incorporation.We selected the 100 most cited guidelines listed on the National Guideline Clearinghouse (http://www.guideline.gov) and determined the number of guidelines that used cost analyses in their reasoning and the overall percentage of incorporation of relevant cost analyses available in PubMed. Differences between medical specialties were also studied. Then, we performed a case-control study using incorporated and not incorporated cost analyses after 1:1 matching by study subject and compared them by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement requirements and other criteria.We found that 57% of guidelines do not use any cost justification. Guidelines incorporate a weighted average of 6.0% (95% confidence interval [CI] 4.3-7.9) among 3396 available cost analyses, with cardiology and infectious diseases guidelines incorporating 10.8% (95% CI 5.3-18.1) and 9.9% (95% CI 3.9- 18.2), respectively, and hematology/oncology and urology guidelines incorporating 4.5% (95% CI 1.6-8.6) and 1.6% (95% CI 0.4-3.5), respectively. Based on the CHEERS requirements, the mean number of items reported by the 148 incorporated cost analyses was 18.6 (SD = 3.7), a small but significant difference over controls (17.8 items; P = 0.02). Included analyses were also more likely to directly relate cost reductions to healthcare outcomes (92.6% vs 81.1%, P = 0.004) and declare the funding source (72.3% vs 53.4%, P < 0.001), while similar number of cases and controls reported a noncommercial funding source (71% vs 72.7%; P = 0.8).Guidelines remain an underused mechanism for the cost-effective allocation of available resources and a minority of practice guidelines incorporates cost analyses utilizing only 6% of the available cost analyses. Fulfilling the CHEERS requirements, directly relating costs with healthcare outcomes and transparently declaring the funding source seem to be valued by guideline-writing committees.

A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies.

PubMed

Bodea, Corneliu A; Neale, Benjamin M; Ripke, Stephan; Daly, Mark J; Devlin, Bernie; Roeder, Kathryn

2016-05-05

One goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in case subjects are contrasted with those from population-based samples used as control subjects. In an ideal world we would know population-level allele frequencies, releasing researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of control subjects from studies of Crohn disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful, and convenient genetic association analyses without access to the individual-level data. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Association between global DNA hypomethylation in leukocytes and risk of breast cancer.

PubMed

Choi, Ji-Yeob; James, Smitha R; Link, Petra A; McCann, Susan E; Hong, Chi-Chen; Davis, Warren; Nesline, Mary K; Ambrosone, Christine B; Karpf, Adam R

2009-11-01

Global DNA hypomethylation may result in chromosomal instability and oncogene activation, and as a surrogate of systemic methylation activity, may be associated with breast cancer risk. Samples and data were obtained from women with incident early-stage breast cancer (I-IIIa) and women who were cancer free, frequency matched on age and race. In preliminary analyses, genomic methylation of leukocyte DNA was determined by measuring 5-methyldeoxycytosine (5-mdC), as well as methylation analysis of the LINE-1-repetitive DNA element. Further analyses used only 5-mdC levels. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of breast cancer in relation to amounts of methylation. In a subset of samples tested (n = 37), 5-mdC level was not correlated with LINE-1 methylation. 5-mdC level in leukocyte DNA was significantly lower in breast cancer cases than healthy controls (P = 0.001), but no significant case-control differences were observed with LINE-1 methylation (P = 0.176). In the entire data set, we noted significant differences in 5-mdC levels in leukocytes between cases (n = 176) and controls (n = 173); P value < 0.001. Compared with women in the highest 5-mdC tertile (T3), women in the second (T2; OR = 1.49, 95% CI = 0.84-2.65) and lowest tertile (T1; OR = 2.86, 95% CI = 1.65-4.94) had higher risk of breast cancer (P for trend < or = 0.001). Among controls only and cases and controls combined, only alcohol intake was found to be inversely associated with methylation levels. These findings suggest that leukocyte DNA hypomethylation is independently associated with development of breast cancer.

The association of factor V leiden mutation with recurrent pregnancy loss.

PubMed

Kashif, Sumreen; Kashif, Muhammad Ali; Saeed, Anjum

2015-11-01

To determine the association of factor V Leiden mutation with recurrent pregnancy loss. The case-control study was conducted at the Department of Haematology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from January to June 2012, and comprised women of 18 to 45 years of age who had a history of recurrent pregnancy loss, and controls with no history of pregnancy loss. All the subjects belonged to Punjabi ethnic group. Three ml blood was taken from cases and controls and deoxyribonucleic acid was extracted. In order to identify Factor V Leiden mutation, polymerase chain reaction method was utilised combined with the amplification refractory mutation system. Data was analysed using SPSS 17. Of the 112 subjects, 56(50%) were in each of the two groups. The presence of factor V Leiden mutation among the cases was 3(5.4%) while it was absent among the controls. The mutation was significantly associated with recurrent pregnancy loss (p=0.017).Recurrent pregnancy loss was higher in cases than controls (p=0.001). Factor V Leiden mutation, Recurrent pregnancy loss, PCR (Polymerase chain reaction).

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

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.

Serum carotenoid and tocopherol concentrations and risk of asthma in childhood: a nested case-control study.

PubMed

Hämäläinen, N; Nwaru, B I; Erlund, I; Takkinen, H-M; Ahonen, S; Toppari, J; Ilonen, J; Veijola, R; Knip, M; Kaila, M; Virtanen, S M

2017-03-01

The antioxidant hypothesis regarding the risk of asthma in childhood has resulted in inconsistent findings. Some data indicate that the role of antioxidants in childhood asthma risk may have a critical time window of effect, but only a well-designed longitudinal cohort study can clarify this hypothesis. To study the longitudinal associations between serum carotenoid and tocopherol concentrations during the first 4 years of life and asthma risk by the age of 5 years. Based on a case-control design nested within a Finnish birth cohort, 146 asthma cases were matched to 270 controls on birth time, sex, genetic risk, and birth place. Non-fasting blood samples were collected at the ages of 1, 1.5, 2, 3, and 4 years and serum carotenoids and tocopherols were analysed. Parents reported the presence and age at start of persistent doctor-diagnosed asthma in the child at the age of 5 years. Data analyses were conducted using generalized estimating equations. We did not find strong associations between serum carotenoids and tocopherols and the risk of asthma based on age-specific and longitudinal analyses. Both lower and higher quarters of α-carotene and γ-tocopherol increased the risk of asthma. The current findings do not support the suggestion that the increased prevalence of asthma may be a consequence of decreased intake of antioxidant nutrients. Moreover, we did not confirm any critical time window of impact of antioxidants on asthma risk. Replication of these findings in similar longitudinal settings will strengthen this evidence base. © 2017 John Wiley & Sons Ltd.

Prostatitis, other genitourinary infections and prostate cancer: results from a population-based case-control study.

PubMed

Boehm, Katharina; Valdivieso, Roger; Meskawi, Malek; Larcher, Alessandro; Schiffmann, Jonas; Sun, Maxine; Graefen, Markus; Saad, Fred; Parent, Marie-Élise; Karakiewicz, Pierre I

2016-03-01

We relied on a population-based case-control study (PROtEuS) to examine a potential association between the presence of histologically confirmed prostate cancer (PCa) and history of genitourinary infections, e.g., prostatitis, urethritis, orchitis and epididymitis. Cases were 1933 men with incident PCa, diagnosed across Montreal hospitals between 2005 and 2009. Population controls were 1994 men from the same residential area and age distribution. In-person interviews collected information about socio-demographic characteristics, lifestyle and medical history, e.g., self-reported history of several genitourinary infections, as well as on PCa screening. Logistic regression analyses tested overall and grade-specific associations, including subgroup analyses with frequent PSA testing. After multivariable adjustment, prostatitis was associated with an increased risk of any PCa (OR 1.81 [1.44-2.27]), but not urethritis (OR 1.05 [0.84-1.30]), orchitis (OR 1.28 [0.92-1.78]) or epididymitis (OR 0.98 [0.57-1.68]). The association between prostatitis and PCa was more pronounced for low-grade PCa (Gleason ≤ 6: OR 2.11 [1.61-2.77]; Gleason ≥ 7: OR 1.59 [1.22-2.07]). Adjusting for frequency of physician visits, PSA testing frequency or restricting analyses to frequently screened subjects did not affect these results. Prostatitis was associated with an increased probability for detecting PCa even after adjustment for frequency of PSA testing and physician visits, but not urethritis, orchitis or epididymitis. These considerations may be helpful in clinical risk stratification of individuals in whom the risk of PCa is pertinent.

Medication exposure and spontaneous abortion: a case-control study using a French medical database.

PubMed

Abadie, D; Hurault-Delarue, C; Damase-Michel, C; Montastruc, J L; Lacroix, I

2015-01-01

Few studies have been conducted to investigate drug effects on spontaneous abortion risk. The objective of the present study was to evaluate the potential association between first trimester drug exposure and spontaneous abortion occurrence. The authors performed a nested case-control study using data from TERAPPEL, a French medical database. Cases were the women who had a spontaneous abortion (before the 22nd week of amenorrhea) and controls were women who gave birth to a child. Analyzed variables were: maternal age, obstetric history, tobacco, and alcohol and drug consumption during the first trimester of pregnancy. For comparison of drug exposures between cases and controls, the authors calculated odds ratios (ORs) by means of multivariate logistic regressions adjusted on age and on other drug exposures. The study included 838 cases and 4,508 controls that were identified in the database. In adjusted analyses, cases were more exposed than controls to "non-selective monoamine reuptake inhibitors" [OR=2.2 (CI 95% 1.5-3.3)], "antiprotozoals" [OR = 1.6 (CI 95% 1.1 - 2.5)] and "centrally acting antiobesity products" [OR = 3.4 (CI 95% 1.9 - 6.2)]. Conversely, controls were more exposed than cases to H1 antihistamines [OR = 0.6 (CI 95% 0.4 - 0.9)]. This exploratory study highlights some potential associations between first trimester drug exposure and risk of spontaneous abortion. Further studies have to be carried out to investigate these findings.

Evaluation of Pneumococcal Load in Blood by Polymerase Chain Reaction for the Diagnosis of Pneumococcal Pneumonia in Young Children in the PERCH Study.

PubMed

Deloria Knoll, Maria; Morpeth, Susan C; Scott, J Anthony G; Watson, Nora L; Park, Daniel E; Baggett, Henry C; Brooks, W Abdullah; Feikin, Daniel R; Hammitt, Laura L; Howie, Stephen R C; Kotloff, Karen L; Levine, Orin S; O'Brien, Katherine L; Thea, Donald M; Ahmed, Dilruba; Antonio, Martin; Awori, Juliet O; Baillie, Vicky L; Chipeta, James; Deluca, Andrea N; Dione, Michel; Driscoll, Amanda J; Higdon, Melissa M; Jatapai, Anchalee; Karron, Ruth A; Mazumder, Razib; Moore, David P; Mwansa, James; Nyongesa, Sammy; Prosperi, Christine; Seidenberg, Phil; Siludjai, Duangkamon; Sow, Samba O; Tamboura, Boubou; Zeger, Scott L; Murdoch, David R; Madhi, Shabir A

2017-06-15

Detection of pneumococcus by lytA polymerase chain reaction (PCR) in blood had poor diagnostic accuracy for diagnosing pneumococcal pneumonia in children in 9 African and Asian sites. We assessed the value of blood lytA quantification in diagnosing pneumococcal pneumonia. The Pneumonia Etiology Research for Child Health (PERCH) case-control study tested whole blood by PCR for pneumococcus in children aged 1-59 months hospitalized with signs of pneumonia and in age-frequency matched community controls. The distribution of load among PCR-positive participants was compared between microbiologically confirmed pneumococcal pneumonia (MCPP) cases, cases confirmed for nonpneumococcal pathogens, nonconfirmed cases, and controls. Receiver operating characteristic analyses determined the "optimal threshold" that distinguished MCPP cases from controls. Load was available for 290 of 291 cases with pneumococcal PCR detected in blood and 273 of 273 controls. Load was higher in MCPP cases than controls (median, 4.0 × 103 vs 0.19 × 103 copies/mL), but overlapped substantially (range, 0.16-989.9 × 103 copies/mL and 0.01-551.9 × 103 copies/mL, respectively). The proportion with high load (≥2.2 log10 copies/mL) was 62.5% among MCPP cases, 4.3% among nonconfirmed cases, 9.3% among cases confirmed for a nonpneumococcal pathogen, and 3.1% among controls. Pneumococcal load in blood was not associated with respiratory tract illness in controls (P = .32). High blood pneumococcal load was associated with alveolar consolidation on chest radiograph in nonconfirmed cases, and with high (>6.9 log10 copies/mL) nasopharyngeal/oropharyngeal load and C-reactive protein ≥40 mg/L (both P < .01) in nonconfirmed cases but not controls. Quantitative pneumococcal PCR in blood has limited diagnostic utility for identifying pneumococcal pneumonia in individual children, but may be informative in epidemiological studies. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Non-solar ultraviolet radiation and the risk of basal and squamous cell skin cancer.

PubMed Central

Bajdik, C. D.; Gallagher, R. P.; Astrakianakis, G.; Hill, G. B.; Fincham, S.; McLean, D. I.

1996-01-01

A case-control study of non-melanocytic skin cancer was conducted among men in the province of Alberta, Canada. Two hundred and twenty-six cases of basal cell carcinoma (BCC), 180 cases of squamous cell carcinoma (SCC) and 406 age-matched controls provided information concerning skin pigmentation, occupational history, recreational activity, exposure to sunlight and sources of non-solar ultraviolet radiation (NSUVR) and other potential risk factors. Our analyses show no evidence of elevated risk for BCC or SCC among subjects exposed to various types of NSUVR. This is in opposition to studies of melanoma that have shown elevated risks for exposure to fluorescent lighting, sunlamps and sunbeds. PMID:8664139

N-acetyltransferase 2 polymorphism and breast cancer risk with smoking: a case control study in Japanese women.

PubMed

Hara, Akio; Taira, Naruto; Mizoo, Taeko; Nishiyama, Keiko; Nogami, Tomohiro; Iwamoto, Takayuki; Motoki, Takayuki; Shien, Tadahiko; Matsuoka, Junji; Doihara, Hiroyoshi; Ishihara, Setsuko; Kawai, Hiroshi; Kawasaki, Kensuke; Ishibe, Youichi; Ogasawara, Yutaka; Miyoshi, Shinichiro

2017-03-01

Recent studies have suggested that the association between smoking and breast cancer risk might be modified by polymorphisms in the N-acetyltransferase 2 gene (NAT2). Most of these studies were conducted in Western countries, with few reports from East Asia. We conducted a case-control study of 511 breast cancer cases and 527 unmatched healthy controls from December 2010 to November 2011 in Japan. Unconditional logistic regression was used to analyze the association of smoking with breast cancer risk stratified by NAT2 phenotype. In this population, 11 % of the cases and 10 % of the controls were classified as a slow acetylator phenotype. Compared to never smokers, current smokers had an increased breast cancer risk in multivariate analysis [odds ratio (OR) = 2.27, 95 % confidence interval (95 %CI) = 1.38-3.82]. Subgroup analyses of menopausal status indicated the same tendency. Subgroup analyses of NAT2 phenotype, the ORs in both of rapid and slow acetylator phenotype subgroups were comparable, and no interactions were observed between smoking status and NAT2 phenotype (p = 0.97). A dose-dependent effect of smoking on breast cancer risk was seen for the rapid acetylator phenotype, but not for the slow acetylator phenotype. Given the high frequency of the rapid acetylator phenotype, these results show that smoking is a risk factor for breast cancer among most Japanese women. It may be of little significance to identify the NAT2 phenotype in the Japanese population.

A retrospective pilot study to determine whether the reproductive tract microbiota differs between women with a history of infertility and fertile women.

PubMed

Wee, Bryan A; Thomas, Mark; Sweeney, Emma Louise; Frentiu, Francesca D; Samios, Melanie; Ravel, Jacques; Gajer, Pawel; Myers, Garry; Timms, Peter; Allan, John A; Huston, Wilhelmina M

2018-06-01

We know very little about the microbiota inhabiting the upper female reproductive tract and how it impacts on fertility. This pilot study aimed to examine the vaginal, cervical and endometrial microbiota for women with a history of infertility compared to women with a history of fertility. Using a retrospective case-control study design, women were recruited for collection of vaginal, cervical and endometrial samples. The microbiota composition was analysed by 16S ribosomal RNA (rRNA) gene amplification and endometrial expression of selected human genes by quantitative reverse transcription polymerase chain reaction. Sixty-five specimens from the reproductive tract of 31 women were successfully analysed using 16S rRNA gene amplicon sequencing (16 controls and 15 cases). The dominant microbial community members were consistent in the vagina and cervix, and generally consistent with the endometrium although the relative proportions varied. We detected three major microbiota clusters that did not group by tissue location or case-control status. There was a trend that infertile women more often had Ureaplasma in the vagina and Gardnerella in the cervix. Testing for the expression of selected genes in the endometrium did not show evidence of correlation with case-control status, or with microbial community composition, although Tenascin-C expression correlated with a history of miscarriage. There is a need for further exploration of the endometrial microbiota, and how the microbiota members or profile interplays with fertility or assisted reproductive technologies. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

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.

Mobile phone use and risk of tumors: a meta-analysis.

PubMed

Myung, Seung-Kwon; Ju, Woong; McDonnell, Diana D; Lee, Yeon Ji; Kazinets, Gene; Cheng, Chih-Tao; Moskowitz, Joel M

2009-11-20

Case-control studies have reported inconsistent findings regarding the association between mobile phone use and tumor risk. We investigated these associations using a meta-analysis. We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library in August 2008. Two evaluators independently reviewed and selected articles based on predetermined selection criteria. Of 465 articles meeting our initial criteria, 23 case-control studies, which involved 37,916 participants (12,344 patient cases and 25,572 controls), were included in the final analyses. Compared with never or rarely having used a mobile phone, the odds ratio for overall use was 0.98 for malignant and benign tumors (95% CI, 0.89 to 1.07) in a random-effects meta-analysis of all 23 studies. However, a significant positive association (harmful effect) was observed in a random-effects meta-analysis of eight studies using blinding, whereas a significant negative association (protective effect) was observed in a fixed-effects meta-analysis of 15 studies not using blinding. Mobile phone use of 10 years or longer was associated with a risk of tumors in 13 studies reporting this association (odds ratio = 1.18; 95% CI, 1.04 to 1.34). Further, these findings were also observed in the subgroup analyses by methodologic quality of study. Blinding and methodologic quality of study were strongly associated with the research group. The current study found that there is possible evidence linking mobile phone use to an increased risk of tumors from a meta-analysis of low-biased case-control studies. Prospective cohort studies providing a higher level of evidence are needed.

Poor Metabolizers at the Cytochrome P450 2C19 Loci Is at Increased Risk of Developing Cancer in Asian Populations

PubMed Central

Chen, Zenggan; Yu, Yanmin

2013-01-01

Background CYP2C19 encodes a member of the cytochrome P450 superfamily of enzymes, which play a central role in activating and detoxifying many carcinogens and endogenous compounds thought to be involved in the development of cancer. In the past decade, two common polymorphisms among CYP2C19 (CYP2C19*2 and CYP2C19*3) that are responsible for the poor metabolizers (PMs) phenotype in humans and cancer susceptibility have been investigated extensively; however, these studies have yielded contradictory results. Methods and Results To investigate this inconsistency, we conducted a comprehensive meta-analysis of 11,554 cases and 16,592 controls from 30 case-control studies. Overall, the odds ratio (OR) of cancer was 1.52 [95% confidence interval (CI): 1.23–1.88, P<10-4] for CYP2C19 PMs genotypes. However, this significant association vanished when the analyses were restricted to 5 larger studies (no. of cases ≥ 500 cases). In the subgroup analysis for different cancer types, PMs genotypes had an effect of increasing the risks of esophagus cancer, gastric cancer, lung cancer and hepatocellular carcinoma as well as head neck cancer. Significant results were found in Asian populations when stratified by ethnicity; whereas no significant associations were found among Caucasians. Stratified analyses according to source of controls, significant associations were found only in hospital base controls. Conclusions Our meta-analysis suggests that the CYP2C19 PMs genotypes most likely contributes to cancer susceptibility, particularly in the Asian populations. PMID:24015291

The relationship between urban environment and the inflammatory bowel diseases: a systematic review and meta-analysis.

PubMed

Soon, Ing Shian; Molodecky, Natalie A; Rabi, Doreen M; Ghali, William A; Barkema, Herman W; Kaplan, Gilaad G

2012-05-24

The objective of this study was to conduct a systematic review with meta-analysis of studies assessing the association between living in an urban environment and the development of the Crohn's disease (CD) or ulcerative colitis (UC). A systematic literature search of MEDLINE (1950-Oct. 2009) and EMBASE (1980-Oct. 2009) was conducted to identify studies investigating the relationship between urban environment and IBD. Cohort and case-control studies were analyzed using incidence rate ratio (IRR) or odds ratio (OR) with 95 % confidence intervals (CIs), respectively. Stratified and sensitivity analyses were performed to explore heterogeneity between studies and assess effects of study quality. The search strategy retrieved 6940 unique citations and 40 studies were selected for inclusion. Of these, 25 investigated the relationship between urban environment and UC and 30 investigated this relationship with CD. Included in our analysis were 7 case-control UC studies, 9 case-control CD studies, 18 cohort UC studies and 21 cohort CD studies. Based on a random effects model, the pooled IRRs for urban compared to rural environment for UC and CD studies were 1.17 (1.03, 1.32) and 1.42 (1.26, 1.60), respectively. These associations persisted across multiple stratified and sensitivity analyses exploring clinical and study quality factors. Heterogeneity was observed in the cohort studies for both UC and CD, whereas statistically significant heterogeneity was not observed for the case-control studies. A positive association between urban environment and both CD and UC was found. Heterogeneity may be explained by differences in study design and quality factors.

Sleep problems and suicide attempts among adolescents: a case-control study.

PubMed

Koyawala, Neel; Stevens, Jack; McBee-Strayer, Sandra M; Cannon, Elizabeth A; Bridge, Jeffrey A

2015-01-01

This study used a case-control design to compare sleep disturbances in 40 adolescents who attempted suicide with 40 never-suicidal adolescents. Using hierarchical logistic regression analyses, we found that self-reported nighttime awakenings were significantly associated with attempted suicide, after controlling for antidepressant use, antipsychotic use, affective problems, and being bullied. In a separate regression analysis, the parent-reported total sleep problems score also predicted suicide attempt status, controlling for key covariates. No associations were found between suicide attempts and other distinct sleep problems, including falling asleep at bedtime, sleeping a lot during the day, trouble waking up in the morning, sleep duration, and parent-reported nightmares. Clinicians should be aware of sleep problems as potential risk factors for suicide attempts for adolescents.

Maoa and Maob polymorphisms and personality traits in suicide attempters and healthy controls: a preliminary study.

PubMed

Balestri, Martina; Calati, Raffaella; Serretti, Alessandro; Hartmann, Annette M; Konte, Bettina; Friedl, Marion; Giegling, Ina; Rujescu, Dan

2017-03-01

Serotonergic neurotransmission dysfunctions have been well documented in patients with suicidal behaviour. We investigated monoamine oxidase A (MAOA: rs2064070, rs6323, rs909525) and B (MAOB: rs1799836, rs2311013, rs2205655) genetic modulation of personality traits (Temperament and Character Inventory, TCI) as endophenotype for suicidal behaviour. 108 suicide attempters and 286 healthy controls of German origin were screened. Among females, allelic analyses revealed associations between MAOA rs6323 A allele and higher Harm Avoidance in suicide attempters and MAOB rs2205655 A allele and higher Cooperativeness scores in healthy controls. Among males, MAOA rs909525 A allele was associated with higher Reward Dependence in suicide attempters. Multivariate analyses controlling for age and educational level mainly confirmed results. Case-control analyses in this subsample do not differ from our previously reported one. Despite of the small sample size, a possible involvement of these genes in the modulation of personality traits closely related to suicidal behaviour cannot be excluded. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

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.

A modified case-control study of cryptosporidiosis (using non-Cryptosporidium-infected enteric cases as controls) in a community setting.

PubMed

Pintar, K D M; Pollari, F; Waltner-Toews, D; Charron, D F; McEwen, S A; Fazil, A; Nesbitt, A

2009-12-01

Data from the first sentinel site (Waterloo Region, Ontario) of the Canadian Integrated Enteric Disease Surveillance System (C-EnterNet) were used in a secondary-based case-control study of laboratory-confirmed Cryptosporidium infections to study the role of various exposure factors. The incidence of cryptosporidiosis in Waterloo Region was almost double both the provincial and national rates. Persons ill with one of nine other enteric infections (amoebiasis, campylobacteriosis, cyclosporiasis, giardiasis, listeriosis, salmonellosis, shigellosis, verotoxigenic E. coli infections, yersiniosis) captured by the surveillance system were used as the control group. Of 1204 cases of enteric illness in the sentinel area between April 2005 and December 2007, 36 cases and 803 controls were selected after excluding outbreak and international travel-related cases. Univariable analyses (Pearson chi2 and Fisher's exact tests) and multivariable logistic regression were performed. Results of the multivariable analysis found that cryptosporidiosis was associated with swimming in a lake or river (OR 2.9, 95% CI 1.2-7.4), drinking municipal water (a potential surrogate for urban respondents vs. rural) (OR 2.4, 95% CI 1.04-5.7), and having a family member with a diarrhoeal illness (OR 2.9, 95% CI 1.3-6.4).

Recall bias in the assessment of exposure to mobile phones.

PubMed

Vrijheid, Martine; Armstrong, Bruce K; Bédard, Daniel; Brown, Julianne; Deltour, Isabelle; Iavarone, Ivano; Krewski, Daniel; Lagorio, Susanna; Moore, Stephen; Richardson, Lesley; Giles, Graham G; McBride, Mary; Parent, Marie-Elise; Siemiatycki, Jack; Cardis, Elisabeth

2009-05-01

Most studies of mobile phone use are case-control studies that rely on participants' reports of past phone use for their exposure assessment. Differential errors in recalled phone use are a major concern in such studies. INTERPHONE, a multinational case-control study of brain tumour risk and mobile phone use, included validation studies to quantify such errors and evaluate the potential for recall bias. Mobile phone records of 212 cases and 296 controls were collected from network operators in three INTERPHONE countries over an average of 2 years, and compared with mobile phone use reported at interview. The ratio of reported to recorded phone use was analysed as measure of agreement. Mean ratios were virtually the same for cases and controls: both underestimated number of calls by a factor of 0.81 and overestimated call duration by a factor of 1.4. For cases, but not controls, ratios increased with increasing time before the interview; however, these trends were based on few subjects with long-term data. Ratios increased by level of use. Random recall errors were large. In conclusion, there was little evidence for differential recall errors overall or in recent time periods. However, apparent overestimation by cases in more distant time periods could cause positive bias in estimates of disease risk associated with mobile phone use.

Australian Schizophrenia Research Bank: a database of comprehensive clinical, endophenotypic and genetic data for aetiological studies of schizophrenia.

PubMed

Loughland, Carmel; Draganic, Daren; McCabe, Kathryn; Richards, Jacqueline; Nasir, Aslam; Allen, Joanne; Catts, Stanley; Jablensky, Assen; Henskens, Frans; Michie, Patricia; Mowry, Bryan; Pantelis, Christos; Schall, Ulrich; Scott, Rodney; Tooney, Paul; Carr, Vaughan

2010-11-01

This article describes the establishment of the Australian Schizophrenia Research Bank (ASRB), which operates to collect, store and distribute linked clinical, cognitive, neuroimaging and genetic data from a large sample of people with schizophrenia and healthy controls. Recruitment sources for the schizophrenia sample include a multi-media national advertising campaign, inpatient and community treatment services and non-government support agencies. Healthy controls have been recruited primarily through multi-media advertisements. All participants undergo an extensive diagnostic and family history assessment, neuropsychological evaluation, and blood sample donation for genetic studies. Selected individuals also complete structural MRI scans. Preliminary analyses of 493 schizophrenia cases and 293 healthy controls are reported. Mean age was 39.54 years (SD = 11.1) for the schizophrenia participants and 37.38 years (SD = 13.12) for healthy controls. Compared to the controls, features of the schizophrenia sample included a higher proportion of males (cases 65.9%; controls 46.8%), fewer living in married or de facto relationships (cases 16.1%; controls 53.6%) and fewer years of education (cases 13.05, SD = 2.84; controls 15.14, SD = 3.13), as well as lower current IQ (cases 102.68, SD = 15.51; controls 118.28, SD = 10.18). These and other sample characteristics are compared to those reported in another large Australian sample (i.e. the Low Prevalence Disorders Study), revealing some differences that reflect the different sampling methods of these two studies. The ASRB is a valuable and accessible schizophrenia research facility for use by approved scientific investigators. As recruitment continues, the approach to sampling for both cases and controls will need to be modified to ensure that the ASRB samples are as broadly representative as possible of all cases of schizophrenia and healthy controls.

Making medical decisions in dependence of genetic background: estimation of the utility of DNA testing in clinical, pharmaco-epidemiological or genetic studies.

PubMed

Nguyen, Thuy Trang; Schäfer, Helmut; Timmesfeld, Nina

2013-05-01

An index measuring the utility of testing a DNA marker before deciding between two alternative treatments is proposed which can be estimated from pharmaco-epidemiological case-control or cohort studies. In the case-control design, external estimates of the prevalence of the disease and of the frequency of the genetic risk variant are required for estimating the utility index. Formulas for point and interval estimates are derived. Empirical coverage probabilities of the confidence intervals were estimated under different scenarios of disease prevalence, prevalence of drug use, and population frequency of the genetic variant. To illustrate our method, we re-analyse pharmaco-epidemiological case-control data on oral contraceptive intake and venous thrombosis in carriers and non-carriers of the factor V Leiden mutation. We also re-analyse cross-sectional data from the Framingham study on a gene-diet interaction between an APOA2 polymorphism and high saturated fat intake on obesity. We conclude that the utility index may be helpful to evaluate and appraise the potential clinical and public health relevance of gene-environment interaction effects detected in genomic and candidate gene association studies and may be a valuable decision support for designing prospective studies on the clinical utility. © 2013 Wiley Periodicals, Inc.

Reducing selection bias in case-control studies from rare disease registries.

PubMed

Cole, J Alexander; Taylor, John S; Hangartner, Thomas N; Weinreb, Neal J; Mistry, Pramod K; Khan, Aneal

2011-09-12

In clinical research of rare diseases, where small patient numbers and disease heterogeneity limit study design options, registries are a valuable resource for demographic and outcome information. However, in contrast to prospective, randomized clinical trials, the observational design of registries is prone to introduce selection bias and negatively impact the validity of data analyses. The objective of the study was to demonstrate the utility of case-control matching and the risk-set method in order to control bias in data from a rare disease registry. Data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry were used as an example. A case-control matching analysis using the risk-set method was conducted to identify two groups of patients with type 1 Gaucher disease in the ICGG Gaucher Registry: patients with avascular osteonecrosis (AVN) and those without AVN. The frequency distributions of gender, decade of birth, treatment status, and splenectomy status were presented for cases and controls before and after matching. Odds ratios (and 95% confidence intervals) were calculated for each variable before and after matching. The application of case-control matching methodology results in cohorts of cases (i.e., patients with AVN) and controls (i.e., patients without AVN) who have comparable distributions for four common parameters used in subject selection: gender, year of birth (age), treatment status, and splenectomy status. Matching resulted in odds ratios of approximately 1.00, indicating no bias. We demonstrated bias in case-control selection in subjects from a prototype rare disease registry and used case-control matching to minimize this bias. Therefore, this approach appears useful to study cohorts of heterogeneous patients in rare disease registries.

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.

Health issues in the Arab American community. Male infertility in Lebanon: a case-controlled study.

PubMed

Kobeissi, Loulou; Inhorn, Marcia C

2007-01-01

The impact of risk factors, such as consanguinity and familial clustering, reproductive infections, traumas, and diseases, lifestyle factors and occupational and war exposures on male infertility, was investigated in a case-controlled study conducted in Lebanon. One-hundred-twenty males and 100 controls of Lebanese, Syrian or Lebanese-Palestinian descents were selected from two in-vitro fertilization (IVF) clinics located in Beirut, Lebanon. All cases suffered from impaired sperm count and function, according to World Health Organization guidelines for semen analysis. Controls were the fertile husbands of infertile women. Data were collected using a semi-structured interview, laboratory blood testing and the results of the most recent semen analysis. Univariate, bivariate and multivariate logistic regression analyses were used for data analysis, along with checks for effect modification and control of confounders. Consanguinity and the familial clustering of male infertility cases, as well as reproductive illnesses and war exposures were independently significant risk factors for male infertility. The odds of having infertility problems in the immediate family were 2.6 times higher in cases than controls. The odds of reproductive illness were 2 times higher in cases than controls. The odds of war exposures were 1.57 times higher in cases than controls. Occupational exposures, such as smoking and caffeine intake, were not shown to be important risk factors. This case-controlled study highlights the importance of investigating the etiology of male infertility in Middle Eastern communities. It suggests the need to expand research on male reproductive health in the Middle East in order to improve the prevention and management of male infertility and other male reproductive health problems.

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.

Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies.

PubMed

Yang, Xiaohong R; Chang-Claude, Jenny; Goode, Ellen L; Couch, Fergus J; Nevanlinna, Heli; Milne, Roger L; Gaudet, Mia; Schmidt, Marjanka K; Broeks, Annegien; Cox, Angela; Fasching, Peter A; Hein, Rebecca; Spurdle, Amanda B; Blows, Fiona; Driver, Kristy; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Peter; Vrieling, Alina; Heikkinen, Tuomas; Aittomäki, Kristiina; Heikkilä, Päivi; Blomqvist, Carl; Lissowska, Jolanta; Peplonska, Beata; Chanock, Stephen; Figueroa, Jonine; Brinton, Louise; Hall, Per; Czene, Kamila; Humphreys, Keith; Darabi, Hatef; Liu, Jianjun; Van 't Veer, Laura J; van Leeuwen, Flora E; Andrulis, Irene L; Glendon, Gord; Knight, Julia A; Mulligan, Anna Marie; O'Malley, Frances P; Weerasooriya, Nayana; John, Esther M; Beckmann, Matthias W; Hartmann, Arndt; Weihbrecht, Sebastian B; Wachter, David L; Jud, Sebastian M; Loehberg, Christian R; Baglietto, Laura; English, Dallas R; Giles, Graham G; McLean, Catriona A; Severi, Gianluca; Lambrechts, Diether; Vandorpe, Thijs; Weltens, Caroline; Paridaens, Robert; Smeets, Ann; Neven, Patrick; Wildiers, Hans; Wang, Xianshu; Olson, Janet E; Cafourek, Victoria; Fredericksen, Zachary; Kosel, Matthew; Vachon, Celine; Cramp, Helen E; Connley, Daniel; Cross, Simon S; Balasubramanian, Sabapathy P; Reed, Malcolm W R; Dörk, Thilo; Bremer, Michael; Meyer, Andreas; Karstens, Johann H; Ay, Aysun; Park-Simon, Tjoung-Won; Hillemanns, Peter; Arias Pérez, Jose Ignacio; Menéndez Rodríguez, Primitiva; Zamora, Pilar; Benítez, Javier; Ko, Yon-Dschun; Fischer, Hans-Peter; Hamann, Ute; Pesch, Beate; Brüning, Thomas; Justenhoven, Christina; Brauch, Hiltrud; Eccles, Diana M; Tapper, William J; Gerty, Sue M; Sawyer, Elinor J; Tomlinson, Ian P; Jones, Angela; Kerin, Michael; Miller, Nicola; McInerney, Niall; Anton-Culver, Hoda; Ziogas, Argyrios; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Yang, Show-Lin; Yu, Jyh-Cherng; Chen, Shou-Tung; Hsu, Giu-Cheng; Haiman, Christopher A; Henderson, Brian E; Le Marchand, Loic; Kolonel, Laurence N; Lindblom, Annika; Margolin, Sara; Jakubowska, Anna; Lubiński, Jan; Huzarski, Tomasz; Byrski, Tomasz; Górski, Bohdan; Gronwald, Jacek; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; Jager, Agnes; Kriege, Mieke; Tilanus-Linthorst, Madeleine M A; Collée, Margriet; Wang-Gohrke, Shan; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Mononen, Kari; Grip, Mervi; Hirvikoski, Pasi; Winqvist, Robert; Mannermaa, Arto; Kosma, Veli-Matti; Kauppinen, Jaana; Kataja, Vesa; Auvinen, Päivi; Soini, Ylermi; Sironen, Reijo; Bojesen, Stig E; Ørsted, David Dynnes; Kaur-Knudsen, Diljit; Flyger, Henrik; Nordestgaard, Børge G; Holland, Helene; Chenevix-Trench, Georgia; Manoukian, Siranoush; Barile, Monica; Radice, Paolo; Hankinson, Susan E; Hunter, David J; Tamimi, Rulla; Sangrajrang, Suleeporn; Brennan, Paul; McKay, James; Odefrey, Fabrice; Gaborieau, Valerie; Devilee, Peter; Huijts, P E A; Tollenaar, R A E M; Seynaeve, C; Dite, Gillian S; Apicella, Carmel; Hopper, John L; Hammet, Fleur; Tsimiklis, Helen; Smith, Letitia D; Southey, Melissa C; Humphreys, Manjeet K; Easton, Douglas; Pharoah, Paul; Sherman, Mark E; Garcia-Closas, Montserrat

2011-02-02

Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors. We pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided. In case-case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ≥ 30 kg/m(2)) in younger women (≤50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors. This study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.

Larger men have larger prostates: Detection bias in epidemiologic studies of obesity and prostate cancer risk

PubMed Central

Rundle, Andrew; Wang, Yun; Sadasivan, Sudha; Chitale, Dhananjay A.; Gupta, Nilesh S.; Tang, Deliang; Rybicki, Benjamin A.

2017-01-01

BACKGROUND Obesity is associated with risk of aggressive prostate cancer (PCa), but not with over-all PCa risk. However, obese men have larger prostates which may lower biopsy accuracy and cause a systematic bias towards the null in epidemiologic studies of over-all risk. METHODS Within a cohort of 6,692 men followed-up after a biopsy or transurethral resection of the prostate (TURP) with benign findings, a nested case-control study was conducted of 495 prostate cancer cases and controls matched on age, race, follow-up duration, biopsy versus TURP and procedure date. Data on body mass index and prostate volume at the time of the initial procedure were abstracted from medical records. RESULTS Prior to consideration of differences in prostate volume, overweight (OR = 1.41; 95% CI 1.01, 1.97) and obese status (OR = 1.59; 95% CI 1.09, 2.33) at the time of the original benign biopsy or TURP were associated with PCa incidence during follow-up. Prostate volume did not significantly moderate the association between body-size and PCa, however it did act as an inverse confounder; adjustment for prostate volume increased the effect size for overweight by 22% (adjusted OR = 1.52; 95% CI 1.08, 2.14) and for obese status by 23% (adjusted OR = 1.77; 95% CI 1.20, 2.62). Larger prostate volume at the time of the original benign biopsy or TURP was inversely associated with PCa incidence during follow-up (OR = 0.92 per 10 cc difference in volume; 95% CI 0.88, 0.97). In analyses that stratified case-control pairs by tumor aggressiveness of the case, prostate volume acted as an inverse confounder in analyses of non-aggressive PCa but not in analyses of aggressive PCa. CONCLUSIONS In studies of obesity and PCa, differences in prostate volume cause a bias towards the null, particularly in analyses of non-aggressive PCa. A pervasive underestimation of the association between obesity and overall PCa risk may exist in the literature. PMID:28349547

Larger men have larger prostates: Detection bias in epidemiologic studies of obesity and prostate cancer risk.

PubMed

Rundle, Andrew; Wang, Yun; Sadasivan, Sudha; Chitale, Dhananjay A; Gupta, Nilesh S; Tang, Deliang; Rybicki, Benjamin A

2017-06-01

Obesity is associated with risk of aggressive prostate cancer (PCa), but not with over-all PCa risk. However, obese men have larger prostates which may lower biopsy accuracy and cause a systematic bias toward the null in epidemiologic studies of over-all risk. Within a cohort of 6692 men followed-up after a biopsy or transurethral resection of the prostate (TURP) with benign findings, a nested case-control study was conducted of 495 prostate cancer cases and controls matched on age, race, follow-up duration, biopsy versus TURP, and procedure date. Data on body mass index and prostate volume at the time of the initial procedure were abstracted from medical records. Prior to consideration of differences in prostate volume, overweight (OR = 1.41; 95%CI 1.01, 1.97), and obese status (OR = 1.59; 95%CI 1.09, 2.33) at the time of the original benign biopsy or TURP were associated with PCa incidence during follow-up. Prostate volume did not significantly moderate the association between body-size and PCa, however it did act as an inverse confounder; adjustment for prostate volume increased the effect size for overweight by 22% (adjusted OR = 1.52; 95%CI 1.08, 2.14) and for obese status by 23% (adjusted OR = 1.77; 95%CI 1.20, 2.62). Larger prostate volume at the time of the original benign biopsy or TURP was inversely associated with PCa incidence during follow-up (OR = 0.92 per 10 cc difference in volume; 95%CI 0.88, 0.97). In analyses that stratified case-control pairs by tumor aggressiveness of the case, prostate volume acted as an inverse confounder in analyses of non-aggressive PCa but not in analyses of aggressive PCa. In studies of obesity and PCa, differences in prostate volume cause a bias toward the null, particularly in analyses of non-aggressive PCa. A pervasive underestimation of the association between obesity and overall PCa risk may exist in the literature. © 2017 Wiley Periodicals, Inc.

Equine grass sickness in Scotland: A case-control study of environmental geochemical risk factors.

PubMed

Wylie, C E; Shaw, D J; Fordyce, F M; Lilly, A; Pirie, R S; McGorum, B C

2016-11-01

We hypothesised that the apparent geographical distribution of equine grass sickness (EGS) is partly attributable to suboptimal levels of soil macro- and trace elements in fields where EGS occurs. If proven, altering levels of particular elements could be used to reduce the risk of EGS. To determine whether the geographical distribution of EGS cases in eastern Scotland is associated with the presence or absence of particular environmental chemical elements. Retrospective time-matched case-control study. This study used data for 455 geo-referenced EGS cases and 910 time-matched controls in eastern Scotland, and geo-referenced environmental geochemical data from the British Geological Survey Geochemical Baseline Survey of the Environment stream sediment (G-BASE) and the James Hutton Institute, National Soil Inventory of Scotland (NSIS) datasets. Multivariable statistical analyses identified clusters of three main elements associated with cases from (i) the G-BASE dataset - higher environmental Ti and lower Zn, and (ii) the NSIS dataset - higher environmental Ti and lower Cr. There was also some evidence from univariable analyses for lower Al, Cd, Cu, Ni and Pb and higher Ca, K, Mo, Na and Se environmental concentrations being associated with a case. Results were complicated by a high degree of correlation between most geochemical elements. The work presented here would appear to reflect soil- not horse-level risk factors for EGS, but due to the complexity of the correlations between elements, further work is required to determine whether these associations reflect causality, and consequently whether interventions to alter concentrations of particular elements in soil, or in grazing horses, could potentially reduce the risk of EGS. The effect of chemical elements on the growth of those soil microorganisms implicated in EGS aetiology also warrants further study. © 2015 The The Authors Equine Veterinary Journal © 2015 EVJ Ltd.

Listening panel agreement and characteristics of lung sounds digitally recorded from children aged 1-59 months enrolled in the Pneumonia Etiology Research for Child Health (PERCH) case-control study.

PubMed

McCollum, Eric D; Park, Daniel E; Watson, Nora L; Buck, W Chris; Bunthi, Charatdao; Devendra, Akash; Ebruke, Bernard E; Elhilali, Mounya; Emmanouilidou, Dimitra; Garcia-Prats, Anthony J; Githinji, Leah; Hossain, Lokman; Madhi, Shabir A; Moore, David P; Mulindwa, Justin; Olson, Dan; Awori, Juliet O; Vandepitte, Warunee P; Verwey, Charl; West, James E; Knoll, Maria D; O'Brien, Katherine L; Feikin, Daniel R; Hammit, Laura L

2017-01-01

Paediatric lung sound recordings can be systematically assessed, but methodological feasibility and validity is unknown, especially from developing countries. We examined the performance of acoustically interpreting recorded paediatric lung sounds and compared sound characteristics between cases and controls. Pneumonia Etiology Research for Child Health staff in six African and Asian sites recorded lung sounds with a digital stethoscope in cases and controls. Cases aged 1-59 months had WHO severe or very severe pneumonia; age-matched community controls did not. A listening panel assigned examination results of normal, crackle, wheeze, crackle and wheeze or uninterpretable, with adjudication of discordant interpretations. Classifications were recategorised into any crackle, any wheeze or abnormal (any crackle or wheeze) and primary listener agreement (first two listeners) was analysed among interpretable examinations using the prevalence-adjusted, bias-adjusted kappa (PABAK). We examined predictors of disagreement with logistic regression and compared case and control lung sounds with descriptive statistics. Primary listeners considered 89.5% of 792 case and 92.4% of 301 control recordings interpretable. Among interpretable recordings, listeners agreed on the presence or absence of any abnormality in 74.9% (PABAK 0.50) of cases and 69.8% (PABAK 0.40) of controls, presence/absence of crackles in 70.6% (PABAK 0.41) of cases and 82.4% (PABAK 0.65) of controls and presence/absence of wheeze in 72.6% (PABAK 0.45) of cases and 73.8% (PABAK 0.48) of controls. Controls, tachypnoea, >3 uninterpretable chest positions, crying, upper airway noises and study site predicted listener disagreement. Among all interpretable examinations, 38.0% of cases and 84.9% of controls were normal (p<0.0001); wheezing was the most common sound (49.9%) in cases. Listening panel and case-control data suggests our methodology is feasible, likely valid and that small airway inflammation is common in WHO pneumonia. Digital auscultation may be an important future pneumonia diagnostic in developing countries.

A serum protein-based algorithm for the detection of Alzheimer disease.

PubMed

O'Bryant, Sid E; Xiao, Guanghua; Barber, Robert; Reisch, Joan; Doody, Rachelle; Fairchild, Thomas; Adams, Perrie; Waring, Steven; Diaz-Arrastia, Ramon

2010-09-01

To develop an algorithm that separates patients with Alzheimer disease (AD) from controls. Longitudinal case-control study. The Texas Alzheimer's Research Consortium project. Patients  We analyzed serum protein-based multiplex biomarker data from 197 patients diagnosed with AD and 203 controls. Main Outcome Measure  The total sample was randomized equally into training and test sets and random forest methods were applied to the training set to create a biomarker risk score. The biomarker risk score had a sensitivity and specificity of 0.80 and 0.91, respectively, and an area under the curve of 0.91 in detecting AD. When age, sex, education, and APOE status were added to the algorithm, the sensitivity, specificity, and area under the curve were 0.94, 0.84, and 0.95, respectively. These initial data suggest that serum protein-based biomarkers can be combined with clinical information to accurately classify AD. A disproportionate number of inflammatory and vascular markers were weighted most heavily in the analyses. Additionally, these markers consistently distinguished cases from controls in significant analysis of microarray, logistic regression, and Wilcoxon analyses, suggesting the existence of an inflammatory-related endophenotype of AD that may provide targeted therapeutic opportunities for this subset of patients.

Misconceptions about HIV infection in Kinshasa (Democratic Republic of Congo): a case-control study on knowledge, attitudes and practices.

PubMed

Carlos, Silvia; Martínez-González, Miguel Ángel; Burgueño, Eduardo; López-Del Burgo, Cristina; Ruíz-Canela, Miguel; Ndarabu, Adolphe; Tshilolo, Léon; Tshiswaka, Philomène; Labarga, Pablo; de Irala, Jokin

2015-08-01

To evaluate the prevalence of HIV-related misconceptions in an outpatient centre of Kinshasa (Democratic Republic of Congo) and analyse the association between these beliefs and HIV infection. A case-control study was carried out from December 2010 until June 2012. We assessed 1630 participants aged 15-49 attending a primary outpatient centre in Kinshasa: 762 HIV Voluntary Counselling and Testing attendees and 868 blood donors. A 59-item questionnaire about knowledge, attitudes and practice was administered during a face-to-face interview, followed by an HIV test. Cases and controls were respondents with a newly diagnosed HIV-positive or HIV-negative test, respectively. Unconditional logistic regression was used to analyse the association between misconceptions and HIV seropositivity. 274 cases and 1340 controls were recruited. Cases were more likely than controls to have a low socioeconomic status, no education, to be divorced/separated or widowed. An association was found between the following variables and HIV seropositivity: having a poor HIV knowledge (adjusted OR=2.79; 95% CI 1.43 to 5.45), not knowing a virus is the cause of AIDS (adjusted OR=2.03; 95% CI 1.38 to 2.98) and reporting more than three HIV-transmission-related misconceptions (adjusted OR=3.30; 95% CI 1.64 to 6.64), such as thinking an HIV-positive person cannot look healthy and that HIV is transmitted by sorcery, God's punishment, a kiss on the mouth, mosquitoes, coughs/sneezes or undercooked food. Despite having access to healthcare services, there are still many people in Kinshasa that have HIV-related misconceptions that increase their HIV risk. Our findings underscore the need for a culturally adapted and gender-orientated basic HIV information into Congolese HIV prevention programmes. 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.

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

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.

Power factor improvement in three-phase networks with unbalanced inductive loads using the Roederstein ESTAmat RPR power factor controller

NASA Astrophysics Data System (ADS)

Diniş, C. M.; Cunţan, C. D.; Rob, R. O. S.; Popa, G. N.

2018-01-01

The paper presents the analysis of a power factor with capacitors banks, without series coils, used for improving power factor for a three-phase and single-phase inductive loads. In the experimental measurements, to improve the power factor, the Roederstein ESTAmat RPR power factor controller can command up to twelve capacitors banks, while experimenting using only six capacitors banks. Six delta capacitors banks with approximately equal reactive powers were used for experimentation. The experimental measurements were carried out with a three-phase power quality analyser which worked in three cases: a case without a controller with all capacitors banks permanently parallel connected with network, and two other cases with power factor controller (one with setting power factor at 0.92 and the other one at 1). When performing experiments with the power factor controller, a current transformer was used to measure the current on one phase (at a more charged or less loaded phase).

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

PubMed Central

Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections immunostained for smooth muscle actin (a marker of arterioles) and CD34 (an endothelial marker), with separate analyses on grey and white matter. A total of 43 834 smooth muscle actin-positive vascular profiles and 603 798 CD34-positive vascular profiles were evaluated. In frontal cortex of cases with hippocampal sclerosis of ageing, smooth muscle actin-immunoreactive arterioles had thicker walls (P < 0.05), larger perimeters (P < 0.03), and larger vessel areas (P < 0.03) than controls. Unlike the arterioles, CD34-immunoreactive capillaries had dimensions that were unchanged in cases with hippocampal sclerosis of ageing versus controls. Arteriolosclerosis appears specific to hippocampal sclerosis of ageing brains, because brains with Alzheimer’s disease pathology did not show the same morphological alterations. We conclude that there may be a pathogenetic change in aged human brain arterioles that impacts multiple brain areas and contributes to hippocampal sclerosis of ageing. PMID:24271328

Occupational asphalt is not associated with head and neck cancer.

PubMed

Fogleman, E V; Eliot, M; Michaud, D S; Nelson, H H; McClean, M D; Langevin, S M; Kelsey, K T

2015-10-01

Epidemiologic studies that evaluate the relationship between occupational asphalt exposure and head and neck cancer have had a limited ability to control for known risk factors such as smoking, alcohol and human papillomavirus (HPV). To better elucidate this relationship by including known risk factors in a large case-control study of head and neck squamous cell carcinoma (HNSCC) from the greater Boston area. We analysed the relationship between occupational asphalt exposure and HNSCC among men in the Greater Boston area of Massachusetts. Analyses were conducted using unconditional multivariable logistic regression, performed with adjustments for age, race, education, smoking, alcohol consumption and HPV serology. There were 753 cases and 913 controls. No associations between HNSCC and occupational asphalt exposure (neither among ever-exposed nor by occupational duration) were observed for exposures in any occupation or those restricted to the construction industry. We also observed no associations in subgroup analyses of never-smokers and ever-smokers. Adjusting for known risk factors further reduced the estimated effect of asphalt exposure on HNSCC risk. We found no evidence for an association between occupational asphalt exposure and HNSCC. The null findings from this well-controlled analysis could suggest that the risk estimates stemming from occupational cohort studies may be overestimated due to uncontrolled confounding and enhance the literature available for weighing cancer risk from occupational exposure to bitumen. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Summary of Dynamic Analyses of Selected NSS Buildings.

DTIC Science & Technology

1980-07-01

AREA & WORK UNIT NUMBERS SRI International! Menlo Park, California 94025 FEMA Work Unit 1151D 12. REPORT DATE 13. NO. OF PAGES 11. CONTROLLING OFFICE...ADDRESS (if deff. I’Om Controlling Office) , 1-,7 77 15a. DECLASSIFICATION /DOWNGRADING SCHEDULE 16. DISTRIBUTION STATEMENT (of this report) Approved for... control the final dynamic failure mechanism when there is adequate anchorage to assure full devel- * opment of the tensile membrane mode. The "/s" case

Effect of HCV on fasting glucose, fasting insulin and peripheral insulin resistance in first 5 years of infection.

PubMed

Ahmed, Naeema; Rashid, Amir; Naveed, Abdul Khaliq; Bashir, Qudsia

2016-02-01

To assess the effects of hepatitis C virus infection in the first 5 years on fasting glucose, fasting insulin and peripheral insulin resistance. The case-control study was conducted at the Army Medical College, Rawalpindi, from December 2011 to November 2012, and comprised subjects recruited from a government hospital in Rawalpindi. The subjects included known cases of hepatitis C virus infection for at least 5 years, and normal healthy controls. Fasting blood samples of all the subjects were collected and analysed for serum fasting insulin and serum fasting glucose levels. Homeostatic model assessment-Insulin resistance was calculated SPSS 11 was used for statistical analysis. Of the 30 subjects, 20(66.6%) were cases, while 10(33.3%) were controls. Serum fasting glucose mean level in cases was 89.55±9.53 compared to 84.40±9.80 in the controls (p=0.188). The mean serum fasting insulin in controls was 7.52±3.23 and 6.79±3.30 in cases (p=0.567). Homeostatic model assessment-Insulin resistance level in controls was 1.60±0.76 and In the cases it was 1.49±0.74 (p=0.695). Peripheral insulin resistance and development of type 2 diabetes as a complication of hepatitis C virus infection was not likely at least within the first five years of infection.

Bad Behavior: Improving Reproducibility in Behavior Testing.

PubMed

Andrews, Anne M; Cheng, Xinyi; Altieri, Stefanie C; Yang, Hongyan

2018-01-24

Systems neuroscience research is increasingly possible through the use of integrated molecular and circuit-level analyses. These studies depend on the use of animal models and, in many cases, molecular and circuit-level analyses. Associated with genetic, pharmacologic, epigenetic, and other types of environmental manipulations. We illustrate typical pitfalls resulting from poor validation of behavior tests. We describe experimental designs and enumerate controls needed to improve reproducibility in investigating and reporting of behavioral phenotypes.

[Petrous bone fracture. Our experience: 1999-2004].

PubMed

Ramírez Sabio, J B; de Paula Vernetta, C; García Sanchís, J M; Callejo García, F J; Cortés Andrés, O; Quilis Quesada, V; Dualde Beltrán, D; Marco Algarra, J

2006-12-01

To review the petrous bone fractures during the last five years (1999-2004) in our hospital, its manage, control, and analysis onf the associated factors. To analyse the managing protocoles and current bibliography. We review 266 temporal bone fractures, 74 with petrous bone association. We analyse these fractures by sex distribution, injurie severity, otorhinolaryngological clinical findings, production mechanism and radiological findings. The cases are discussed and compared with current bibliography. Petrous bone fractures must be always suspected in patients with head trauma, specially if it associates severity and otorrhagia. It is necessary a deep colaboration between neurosurgeons, radiologists and otorhinolaryngologists to obtain a good management, control and follow up of the patients.

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.

Risk factors associated with incidence and persistence of signs and symptoms of temporomandibular disorders.

PubMed

Marklund, Susanna; Wänman, Anders

2010-09-01

To analyze whether gender, self-reported bruxism, and variations in dental occlusion predicted incidence and persistence of temporomandibular disorder (TMD) during a 2-year period. The study population comprised 280 dental students at Umeå University in Sweden. The study design was that of a case-control study within a 2-year prospective cohort. The investigation comprised a questionnaire and a clinical examination at enrolment and at 12 and 24 months. Cases (incidence) and controls (no incidence) were identified among those without signs and symptoms of TMD at the start of the study. Cases with 2-year persistence of signs and symptoms of TMD were those with such signs and symptoms at all three examinations. Clinical registrations of baseline variables were used as independent variables. Odds ratio estimates and 95% confidence intervals of the relative risks of being a case or control in relation to baseline registrations were calculated using logistic regression analyses. The analyses revealed that self-reported bruxism and crossbite, respectively increased the risk of the 2-year cumulative incidence and duration of temporomandibular joint (TMJ) signs or symptoms. Female gender was related to an increased risk of developing and maintaining myofascial pain. Signs of mandibular instability increased the risk of maintained TMD signs and symptoms during the observation period. This 2-year prospective observational study indicated that self-reported bruxism and variations in dental occlusion were linked to the incidence and persistence of TMJ signs and symptoms to a higher extent than to myofascial pain.

The utility of the Kohlman Evaluation of Living Skills test is associated with substantiated cases of elder self-neglect.

PubMed

Pickens, Sabrina; Naik, Aanand D; Burnett, Jason; Kelly, P A; Gleason, Mary; Dyer, Carmel B

2007-03-01

Self-neglect is the most prevalent finding among cases reported to Adult Protective Services (APS) and is characterized by an inability to meet one's own basic needs. The Kohlman evaluation of living skills (KELS) has been validated in geriatric populations to assess performance with both instrumental and basic activities of daily living and as an assessment tool for the capacity to live independently; therefore, the purpose of this analysis was to compare the scores of the KELS between substantiated cases of self-neglect and matched community-dwelling elders. This is a cross-sectional pilot study of 50 adults aged 65 years and older who were recruited from APS as documented cases of self-neglect and 50 control participants recruited from Harris County Hospital District outpatient clinics. Control participants were matched for age, race, gender, and ZIP code. A geriatric nurse practitioner (NP)-led team administered a comprehensive geriatric assessment in homes of all study participants. The assessment included the KELS and mini-mental state examination (MMSE) tests. Chi-square analyses were used to determine if cases of self-neglect were significantly more likely to fail the KELS test than matched controls. The analyses revealed that self-neglectors were significantly more likely to fail the KELS than non-self-neglectors (50% vs. 30%, p = .025). When stratified by MMSE scores, self-neglectors with intact cognitive function remained significantly more likely to fail the KELS compared to matched, cognitively intact controls (45% vs. 17%, p = .013). Abnormal results using an in-home KELS test were significantly associated with substantiated cases of self-neglect. There is currently no gold-standard measure for identifying capacity with self-care behaviors among cases of self-neglect. As a result, self-neglect may remain unidentified in many clinical settings. The KELS provides clinicians with an objective measure of an individual's capacity and performance with everyday life-supporting tasks and thus, provides information that can help NPs identify elders at risk for self-neglect. These findings suggest that the KELS test has significant utility as part of a comprehensive geriatric assessment to aid clinicians in suspected cases of self-neglect.

Learning skills and academic performance in children and adolescents with absence epilepsy.

PubMed

Talero-Gutiérrez, C; Sánchez-Torres, J M; Velez-van-Meerbeke, A

2015-03-01

Although cognitive and learning disorders have been described in patients with epilepsy, very few studies focus on specific disorders such as absence epilepsy. The aim of this study was to evaluate learning skills and academic performance in children and adolescents with absence epilepsy. Observational case-control study. Cases were chosen from the Central League against Epilepsy's clinic in Bogotá, Colombia. Controls were selected from a private school and matched with cases by age, school year, and sex. Medical history, seizure frequency, antiepileptic treatment, and academic performance were assessed. Academic abilities were tested with Batería de Aptitudes Diferenciales y Generales (BADyG) (a Spanish-language test of differential and general aptitudes). Data were analysed using Student t-test. The sample consisted of 19 cases and 19 controls aged between 7 and 16. In 15 patients, seizures were controlled; all patients had received antiepileptic medication at some point and 78.9% were actively being treated. Although cases had higher rates of academic failure, a greater incidence of grade retention, and more therapeutic interventions than controls, these differences were not significant. Similarly, there were no significant differences on the BADyG test, except for the immediate memory subcategory on which cases scored higher than controls (P=.0006). Children treated pharmacologically for absence epilepsy, whose seizures are controlled, have normal academic abilities and skills for their age. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Using full-cohort data in nested case-control and case-cohort studies by multiple imputation.

PubMed

Keogh, Ruth H; White, Ian R

2013-10-15

In many large prospective cohorts, expensive exposure measurements cannot be obtained for all individuals. Exposure-disease association studies are therefore often based on nested case-control or case-cohort studies in which complete information is obtained only for sampled individuals. However, in the full cohort, there may be a large amount of information on cheaply available covariates and possibly a surrogate of the main exposure(s), which typically goes unused. We view the nested case-control or case-cohort study plus the remainder of the cohort as a full-cohort study with missing data. Hence, we propose using multiple imputation (MI) to utilise information in the full cohort when data from the sub-studies are analysed. We use the fully observed data to fit the imputation models. We consider using approximate imputation models and also using rejection sampling to draw imputed values from the true distribution of the missing values given the observed data. Simulation studies show that using MI to utilise full-cohort information in the analysis of nested case-control and case-cohort studies can result in important gains in efficiency, particularly when a surrogate of the main exposure is available in the full cohort. In simulations, this method outperforms counter-matching in nested case-control studies and a weighted analysis for case-cohort studies, both of which use some full-cohort information. Approximate imputation models perform well except when there are interactions or non-linear terms in the outcome model, where imputation using rejection sampling works well. Copyright © 2013 John Wiley & Sons, Ltd.

Heavy Metal Risk Management: Case Analysis

PubMed Central

Kim, Ji Ae; Lee, Seung Ha; Choi, Seung Hyun; Jung, Ki Kyung; Park, Mi Sun; Jeong, Ji Yoon; Hwang, Myung Sil; Yoon, Hae Jung; Choi, Dal Woong

2012-01-01

To prepare measures for practical policy utilization and the control of heavy metals, hazard control related institutions by country, present states of control by country, and present states of control by heavy metals were examined. Hazard control cases by heavy metals in various countries were compared and analyzed. In certain countries (e.g., the U.S., the U.K., and Japan), hazardous substances found in foods (e.g., arsenic, lead, cadmium, and mercury) are controlled. In addition, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) recommends calculating the provisional tolerable weekly intake (PTWI) of individual heavy metals instead of the acceptable daily intake (ADI) to compare their pollution levels considering their toxicity accumulated in the human body. In Korea, exposure assessments have been conducted, and in other countries, hazardous substances are controlled by various governing bodies. As such, in Korea and other countries, diverse food heavy metal monitoring and human body exposure assessments are conducted, and reducing measures are prepared accordingly. To reduce the danger of hazardous substances, many countries provide leaflets and guidelines, develop hazardous heavy metal intake recommendations, and take necessary actions. Hazard control case analyses can assist in securing consumer safety by establishing systematic and reliable hazard control methods. PMID:24278603

Neuropathological findings processed by artificial neural networks (ANNs) can perfectly distinguish Alzheimer's patients from controls in the Nun Study

PubMed Central

Grossi, Enzo; Buscema, Massimo P; Snowdon, David; Antuono, Piero

2007-01-01

Background Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this study is to discover the hidden and non-linear associations among AD pathognomonic brain lesions and the clinical diagnosis of AD in participants in the Nun Study through Artificial Neural Networks (ANNs) analysis Methods The analyses were based on 26 clinically- and pathologically-confirmed AD cases and 36 controls who had normal cognitive function. The inputs used for the analyses were just NFT and neuritic plaques counts in neocortex and hippocampus, for which, despite substantial differences in mean lesions counts between AD cases and controls, there was a substantial overlap in the range of lesion counts. Results By taking into account the above four neuropathological features, the overall predictive capability of ANNs in sorting out AD cases from normal controls reached 100%. The corresponding accuracy obtained with Linear Discriminant Analysis was 92.30%. These results were consistently obtained in ten independent experiments. The same experiments were carried out with ANNs on a subgroup of 13 non severe AD patients and on the same 36 controls. The results obtained in terms of prediction accuracy with ANNs were exactly the same. Input relevance analysis confirmed the relative dominance of NFT in neocortex in discriminating between AD patients and controls and indicated the lesser importance played by NP in the hippocampus. Conclusion The results of this study suggest that: a) cortical NFT represent the key variable in AD neuropathology; b) the neuropathologic profile of AD subjects is complex, however, c) ANNs can analyze neuropathologic features and differentiate AD cases from controls. PMID:17584929

Neuropathological findings processed by artificial neural networks (ANNs) can perfectly distinguish Alzheimer's patients from controls in the Nun Study.

PubMed

Grossi, Enzo; Buscema, Massimo P; Snowdon, David; Antuono, Piero

2007-06-21

Many reports have described that there are fewer differences in AD brain neuropathologic lesions between AD patients and control subjects aged 80 years and older, as compared with the considerable differences between younger persons with AD and controls. In fact some investigators have suggested that since neurofibrillary tangles (NFT) can be identified in the brains of non-demented elderly subjects they should be considered as a consequence of the aging process. At present, there are no universally accepted neuropathological criteria which can mathematically differentiate AD from healthy brain in the oldest old. The aim of this study is to discover the hidden and non-linear associations among AD pathognomonic brain lesions and the clinical diagnosis of AD in participants in the Nun Study through Artificial Neural Networks (ANNs) analysis The analyses were based on 26 clinically- and pathologically-confirmed AD cases and 36 controls who had normal cognitive function. The inputs used for the analyses were just NFT and neuritic plaques counts in neocortex and hippocampus, for which, despite substantial differences in mean lesions counts between AD cases and controls, there was a substantial overlap in the range of lesion counts. By taking into account the above four neuropathological features, the overall predictive capability of ANNs in sorting out AD cases from normal controls reached 100%. The corresponding accuracy obtained with Linear Discriminant Analysis was 92.30%. These results were consistently obtained in ten independent experiments. The same experiments were carried out with ANNs on a subgroup of 13 non severe AD patients and on the same 36 controls. The results obtained in terms of prediction accuracy with ANNs were exactly the same. Input relevance analysis confirmed the relative dominance of NFT in neocortex in discriminating between AD patients and controls and indicated the lesser importance played by NP in the hippocampus. The results of this study suggest that: a) cortical NFT represent the key variable in AD neuropathology; b) the neuropathologic profile of AD subjects is complex, however, c) ANNs can analyze neuropathologic features and differentiate AD cases from controls.

Effect of telehealth on quality of life and psychological outcomes over 12 months (Whole Systems Demonstrator telehealth questionnaire study): nested study of patient reported outcomes in a pragmatic, cluster randomised controlled trial.

PubMed

Cartwright, Martin; Hirani, Shashivadan P; Rixon, Lorna; Beynon, Michelle; Doll, Helen; Bower, Peter; Bardsley, Martin; Steventon, Adam; Knapp, Martin; Henderson, Catherine; Rogers, Anne; Sanders, Caroline; Fitzpatrick, Ray; Barlow, James; Newman, Stanton P

2013-02-26

To assess the effect of second generation, home based telehealth on health related quality of life, anxiety, and depressive symptoms over 12 months in patients with long term conditions. A study of patient reported outcomes (the Whole Systems Demonstrator telehealth questionnaire study; baseline n=1573) was nested in a pragmatic, cluster randomised trial of telehealth (the Whole Systems Demonstrator telehealth trial, n=3230). General practice was the unit of randomisation, and telehealth was compared with usual care. Data were collected at baseline, four months (short term), and 12 months (long term). Primary intention to treat analyses tested treatment effectiveness; multilevel models controlled for clustering by general practice and a range of covariates. Analyses were conducted for 759 participants who completed questionnaire measures at all three time points (complete case cohort) and 1201 who completed the baseline assessment plus at least one other assessment (available case cohort). Secondary per protocol analyses tested treatment efficacy and included 633 and 1108 participants in the complete case and available case cohorts, respectively. Provision of primary and secondary care via general practices, specialist nurses, and hospital clinics in three diverse regions of England (Cornwall, Kent, and Newham), with established integrated health and social care systems. Patients with chronic obstructive pulmonary disease (COPD), diabetes, or heart failure recruited between May 2008 and December 2009. Generic, health related quality of life (assessed by physical and mental health component scores of the SF-12, and the EQ-5D), anxiety (assessed by the six item Brief State-Trait Anxiety Inventory), and depressive symptoms (assessed by the 10 item Centre for Epidemiological Studies Depression Scale). In the intention to treat analyses, differences between treatment groups were small and non-significant for all outcomes in the complete case (0.480 ≤ P ≤ 0.904) or available case (0.181 ≤ P ≤ 0.905) cohorts. The magnitude of differences between trial arms did not reach the trial defined, minimal clinically important difference (0.3 standardised mean difference) for any outcome in either cohort at four or 12 months. Per protocol analyses replicated the primary analyses; the main effect of trial arm (telehealth v usual care) was non-significant for any outcome (complete case cohort 0.273 ≤ P ≤ 0.761; available case cohort 0.145 ≤ P ≤ 0.696). Second generation, home based telehealth as implemented in the Whole Systems Demonstrator Evaluation was not effective or efficacious compared with usual care only. Telehealth did not improve quality of life or psychological outcomes for patients with chronic obstructive pulmonary disease, diabetes, or heart failure over 12 months. The findings suggest that concerns about potentially deleterious effect of telehealth are unfounded for most patients. ISRCTN43002091.

Outbreak of acute renal failure in Panama in 2006: a case-control study.

PubMed

Rentz, E Danielle; Lewis, Lauren; Mujica, Oscar J; Barr, Dana B; Schier, Joshua G; Weerasekera, Gayanga; Kuklenyik, Peter; McGeehin, Michael; Osterloh, John; Wamsley, Jacob; Lum, Washington; Alleyne, Camilo; Sosa, Nestor; Motta, Jorge; Rubin, Carol

2008-10-01

In September 2006, a Panamanian physician reported an unusual number of patients with unexplained acute renal failure frequently accompanied by severe neurological dysfunction. Twelve (57%) of 21 patients had died of the illness. This paper describes the investigation into the cause of the illness and the source of the outbreak. Case-control and laboratory investigations were implemented. Case patients (with acute renal failure of unknown etiology and serum creatinine > 2 mg/dl) were individually matched to hospitalized controls for age (+/- 5 years), sex and admission date (< 2 days before the case patient). Questionnaire and biological data were collected. The main outcome measure was the odds of ingesting prescription cough syrup in cases and controls. Forty-two case patients and 140 control patients participated. The median age of cases was 68 years (range: 25-91 years); 64% were male. After controlling for pre-existing hypertension and renal disease and the use of angiotensin-converting enzyme inhibitors, a significant association was found between ingestion of prescription cough syrup and illness onset (adjusted odds ratio: 31.0, 95% confidence interval: 6.93-138). Laboratory analyses confirmed the presence of diethylene glycol (DEG) in biological samples from case patients, 8% DEG contamination in cough syrup samples and 22% contamination in the glycerin used to prepare the cough syrup. The source of the outbreak was DEG-contaminated cough syrup. This investigation led to the recall of approximately 60 000 bottles of contaminated cough syrup, widespread screening of potentially exposed consumers and treatment of over 100 affected patients.

Genome-wide association analysis of secondary imaging phenotypes from the Alzheimer's disease neuroimaging initiative study.

PubMed

Zhu, Wensheng; Yuan, Ying; Zhang, Jingwen; Zhou, Fan; Knickmeyer, Rebecca C; Zhu, Hongtu

2017-02-01

The aim of this paper is to systematically evaluate a biased sampling issue associated with genome-wide association analysis (GWAS) of imaging phenotypes for most imaging genetic studies, including the Alzheimer's Disease Neuroimaging Initiative (ADNI). Specifically, the original sampling scheme of these imaging genetic studies is primarily the retrospective case-control design, whereas most existing statistical analyses of these studies ignore such sampling scheme by directly correlating imaging phenotypes (called the secondary traits) with genotype. Although it has been well documented in genetic epidemiology that ignoring the case-control sampling scheme can produce highly biased estimates, and subsequently lead to misleading results and suspicious associations, such findings are not well documented in imaging genetics. We use extensive simulations and a large-scale imaging genetic data analysis of the Alzheimer's Disease Neuroimaging Initiative (ADNI) data to evaluate the effects of the case-control sampling scheme on GWAS results based on some standard statistical methods, such as linear regression methods, while comparing it with several advanced statistical methods that appropriately adjust for the case-control sampling scheme. Copyright © 2016 Elsevier Inc. All rights reserved.

Three ulcerative colitis susceptibility loci are associated with primary sclerosing cholangitis and indicate a role for IL2, REL, and CARD9.

PubMed

Janse, Marcel; Lamberts, Laetitia E; Franke, Lude; Raychaudhuri, Soumya; Ellinghaus, Eva; Muri Boberg, Kirsten; Melum, Espen; Folseraas, Trine; Schrumpf, Erik; Bergquist, Annika; Björnsson, Einar; Fu, Jingyuan; Jan Westra, Harm; Groen, Harry J M; Fehrmann, Rudolf S N; Smolonska, Joanna; van den Berg, Leonard H; Ophoff, Roel A; Porte, Robert J; Weismüller, Tobias J; Wedemeyer, Jochen; Schramm, Christoph; Sterneck, Martina; Günther, Rainer; Braun, Felix; Vermeire, Severine; Henckaerts, Liesbet; Wijmenga, Cisca; Ponsioen, Cyriel Y; Schreiber, Stefan; Karlsen, Tom H; Franke, Andre; Weersma, Rinse K

2011-06-01

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts. Both environmental and genetic factors contribute to its pathogenesis. To further clarify its genetic background, we investigated susceptibility loci recently identified for ulcerative colitis (UC) in a large cohort of 1,186 PSC patients and 1,748 controls. Single nucleotide polymorphisms (SNPs) tagging 13 UC susceptibility loci were initially genotyped in 854 PSC patients and 1,491 controls from Benelux (331 cases, 735 controls), Germany (265 cases, 368 controls), and Scandinavia (258 cases, 388 controls). Subsequently, a joint analysis was performed with an independent second Scandinavian cohort (332 cases, 257 controls). SNPs at chromosomes 2p16 (P-value 4.12 × 10(-4) ), 4q27 (P-value 4.10 × 10(-5) ), and 9q34 (P-value 8.41 × 10(-4) ) were associated with PSC in the joint analysis after correcting for multiple testing. In PSC patients without inflammatory bowel disease (IBD), SNPs at 4q27 and 9q34 were nominally associated (P < 0.05). We applied additional in silico analyses to identify likely candidate genes at PSC susceptibility loci. To identify nonrandom, evidence-based links we used GRAIL (Gene Relationships Across Implicated Loci) analysis showing interconnectivity between genes in six out of in total nine PSC-associated regions. Expression quantitative trait analysis from 1,469 Dutch and UK individuals demonstrated that five out of nine SNPs had an effect on cis-gene expression. These analyses prioritized IL2, CARD9, and REL as novel candidates. We have identified three UC susceptibility loci to be associated with PSC, harboring the putative candidate genes REL, IL2, and CARD9. These results add to the scarce knowledge on the genetic background of PSC and imply an important role for both innate and adaptive immunological factors. Copyright © 2011 American Association for the Study of Liver Diseases.

Nested case–control study of the effects of non-steroidal anti-inflammatory drugs on breast cancer risk and stage

PubMed Central

Sharpe, C R; Collet, J-P; McNutt, M; Belzile, E; Boivin, J-F; Hanley, J A

2000-01-01

We carried out a nested case–control study to measure the rate ratio (RR) for invasive female breast cancer in relation to non-steroidal anti-inflammatory drug (NSAID) use. The source population consisted of the female beneficiaries of the Saskatchewan Prescription Drug Plan from 1981 to 1995 with no history of cancer since 1970. Four controls/case, matched on age and sampling time, were randomly selected. Dispensing rates during successive time periods characterized NSAID exposure. RRs associated with exposure during each period were adjusted for exposure during the others. Confounding by other determinants was studied in analyses adjusted with data obtained by interviewing samples of subjects accrued from mid-1991 to mid-1995. We accrued 5882 cases and 23 517 controls. Increasing NSAID exposure 2–5 years preceding diagnosis was associated with a trend towards a decreasing RR (P -trend = 0.003); for the highest exposure level RR = 0.76, 95% confidence interval 0.63–0.92. This protective effect could not be attributed to confounding by other determinants. In analyses involving only the cases, NSAID exposure 2–5 and 6–10 years preceding diagnosis was associated with significantly reduced risks of presenting with a large tumour (> 5 cm diameter) or distant metastasis, but not regional lymph node metastasis. The use of NSAIDs may retard the growth of breast cancers and prevent distant metastasis. © 2000 Cancer Research Campaign PMID:10883678

The response of numerical weather prediction analysis systems to FGGE 2b data

NASA Technical Reports Server (NTRS)

Hollingsworth, A.; Lorenc, A.; Tracton, S.; Arpe, K.; Cats, G.; Uppala, S.; Kallberg, P.

1985-01-01

An intercomparison of analyses of the main PGGE Level IIb data set is presented with three advanced analysis systems. The aims of the work are to estimate the extent and magnitude of the differences between the analyses, to identify the reasons for the differences, and finally to estimate the significance of the differences. Extratropical analyses only are considered. Objective evaluations of analysis quality, such as fit to observations, statistics of analysis differences, and mean fields are discussed. In addition, substantial emphasis is placed on subjective evaluation of a series of case studies that were selected to illustrate the importance of different aspects of the analysis procedures, such as quality control, data selection, resolution, dynamical balance, and the role of the assimilating forecast model. In some cases, the forecast models are used as selective amplifiers of analysis differences to assist in deciding which analysis was more nearly correct in the treatment of particular data.

The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort

PubMed Central

Roura, Esther; Travier, Noémie; Waterboer, Tim; de Sanjosé, Silvia; Bosch, F. Xavier; Pawlita, Michael; Pala, Valeria; Weiderpass, Elisabete; Margall, Núria; Dillner, Joakim; Gram, Inger T.; Tjønneland, Anne; Munk, Christian; Palli, Domenico; Khaw, Kay-Tee; Overvad, Kim; Clavel-Chapelon, Françoise; Mesrine, Sylvie; Fournier, Agnès; Fortner, Renée T.; Ose, Jennifer; Steffen, Annika; Trichopoulou, Antonia; Lagiou, Pagona; Orfanos, Philippos; Masala, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Polidoro, Silvia; Mattiello, Amalia; Lund, Eiliv; Peeters, Petra H.; Bueno-de-Mesquita, H. B(as).; Quirós, J. Ramón; Sánchez, María-José; Navarro, Carmen; Barricarte, Aurelio; Larrañaga, Nerea; Ekström, Johanna; Lindquist, David; Idahl, Annika; Travis, Ruth C.; Merritt, Melissa A.; Gunter, Marc J.; Rinaldi, Sabina; Tommasino, Massimo; Franceschi, Silvia; Riboli, Elio; Castellsagué, Xavier

2016-01-01

Background In addition to HPV, high parity and hormonal contraceptives have been associated with cervical cancer (CC). However, most of the evidence comes from retrospective case-control studies. The aim of this study is to prospectively evaluate associations between hormonal factors and risk of developing cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ (CIS) and invasive cervical cancer (ICC). Methods and Findings We followed a cohort of 308,036 women recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study. At enrollment, participants completed a questionnaire and provided serum. After a 9-year median follow-up, 261 ICC and 804 CIN3/CIS cases were reported. In a nested case-control study, the sera from 609 cases and 1,218 matched controls were tested for L1 antibodies against HPV types 11,16,18,31,33,35,45,52,58, and antibodies against Chlamydia trachomatis and Human herpesvirus 2. Multivariate analyses were performed to estimate hazard ratios (HR), odds ratios (OR) and corresponding 95% confidence intervals (CI). The cohort analysis showed that number of full-term pregnancies was positively associated with CIN3/CIS risk (p-trend = 0.03). Duration of oral contraceptives use was associated with a significantly increased risk of both CIN3/CIS and ICC (HR = 1.6 and HR = 1.8 respectively for ≥15 years versus never use). Ever use of menopausal hormone therapy was associated with a reduced risk of ICC (HR = 0.5, 95%CI: 0.4–0.8). A non-significant reduced risk of ICC with ever use of intrauterine devices (IUD) was found in the nested case-control analysis (OR = 0.6). Analyses restricted to all cases and HPV seropositive controls yielded similar results, revealing a significant inverse association with IUD for combined CIN3/CIS and ICC (OR = 0.7). Conclusions Even though HPV is the necessary cause of CC, our results suggest that several hormonal factors are risk factors for cervical carcinogenesis. Adherence to current cervical cancer screening guidelines should minimize the increased risk of CC associated with these hormonal risk factors. PMID:26808155

Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry

PubMed Central

Figueroa, Jonine D.; Middlebrooks, Candace D.; Banday, A. Rouf; Ye, Yuanqing; Garcia-Closas, Montserrat; Chatterjee, Nilanjan; Koutros, Stella; Kiemeney, Lambertus A.; Rafnar, Thorunn; Bishop, Timothy; Furberg, Helena; Matullo, Giuseppe; Golka, Klaus; Gago-Dominguez, Manuela; Taylor, Jack A.; Fletcher, Tony; Siddiq, Afshan; Cortessis, Victoria K.; Kooperberg, Charles; Cussenot, Olivier; Benhamou, Simone; Prescott, Jennifer; Porru, Stefano; Dinney, Colin P.; Malats, Núria; Baris, Dalsu; Purdue, Mark P.; Jacobs, Eric J.; Albanes, Demetrius; Wang, Zhaoming; Chung, Charles C.; Vermeulen, Sita H.; Aben, Katja K.; Galesloot, Tessel E.; Thorleifsson, Gudmar; Sulem, Patrick; Stefansson, Kari; Kiltie, Anne E.; Harland, Mark; Teo, Mark; Offit, Kenneth; Vijai, Joseph; Bajorin, Dean; Kopp, Ryan; Fiorito, Giovanni; Guarrera, Simonetta; Sacerdote, Carlotta; Selinski, Silvia; Hengstler, Jan G.; Gerullis, Holger; Ovsiannikov, Daniel; Blaszkewicz, Meinolf; Castelao, Jose Esteban; Calaza, Manuel; Martinez, Maria Elena; Cordeiro, Patricia; Xu, Zongli; Panduri, Vijayalakshmi; Kumar, Rajiv; Gurzau, Eugene; Koppova, Kvetoslava; Bueno-De-Mesquita, H. Bas; Ljungberg, Börje; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth C.; Tjønneland, Anne; Brennan, Paul; Chang-Claude, Jenny; Riboli, Elio; Conti, David; Stern, Marianna C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Hohensee, Chancellor; Jeppson, Rebecca P.; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Turman, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Kamat, Ashish M.; Zhang, Liren; Gong, Yilei; Pu, Xia; Hutchinson, Amy; Burdett, Laurie; Wheeler, William A.; Karagas, Margaret R.; Johnson, Alison; Schned, Alan; Monawar Hosain, G. M.; Schwenn, Molly; Kogevinas, Manolis; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Andriole, Gerald; Grubb, Robert; Black, Amanda; Diver, W. Ryan; Gapstur, Susan M.; Weinstein, Stephanie; Virtamo, Jarmo; Haiman, Christopher A.; Landi, Maria Teresa; Caporaso, Neil E.; Fraumeni, Joseph F.; Vineis, Paolo; Wu, Xifeng; Chanock, Stephen J.; Silverman, Debra T.; Prokunina-Olsson, Ludmila; Rothman, Nathaniel

2016-01-01

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10−6), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10−11) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10−10). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region—the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r2 = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case–case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer. PMID:26732427

Biomarker discovery study design for type 1 diabetes in The Environmental Determinants of Diabetes in the Young (TEDDY) study.

PubMed

Lee, Hye-Seung; Burkhardt, Brant R; McLeod, Wendy; Smith, Susan; Eberhard, Chris; Lynch, Kristian; Hadley, David; Rewers, Marian; Simell, Olli; She, Jin-Xiong; Hagopian, Bill; Lernmark, Ake; Akolkar, Beena; Ziegler, Anette G; Krischer, Jeffrey P

2014-07-01

The Environmental Determinants of Diabetes in the Young planned biomarker discovery studies on longitudinal samples for persistent confirmed islet cell autoantibodies and type 1 diabetes using dietary biomarkers, metabolomics, microbiome/viral metagenomics and gene expression. This article describes the details of planning The Environmental Determinants of Diabetes in the Young biomarker discovery studies using a nested case-control design that was chosen as an alternative to the full cohort analysis. In the frame of a nested case-control design, it guides the choice of matching factors, selection of controls, preparation of external quality control samples and reduction of batch effects along with proper sample allocation. Our design is to reduce potential bias and retain study power while reducing the costs by limiting the numbers of samples requiring laboratory analyses. It also covers two primary end points (the occurrence of diabetes-related autoantibodies and the diagnosis of type 1 diabetes). The resulting list of case-control matched samples for each laboratory was augmented with external quality control samples. Copyright © 2013 John Wiley & Sons, Ltd.

Neonatal hypoglycemia in term, nondiabetic pregnancies.

PubMed

DePuy, Amy M; Coassolo, Kara M; Som, Dara A; Smulian, John C

2009-05-01

To define the incidence of hypoglycemia and identify risk factors in neonates from term, singleton, nondiabetic pregnancies. We conducted a matched case-control study of term, singleton infants weighing more than 2500 g in nondiabetic pregnancies. Cases with hypoglycemia (glucose < 50 mg/dL) were identified by International Classification of Diseases, ninth revision, codes. Two controls per case were matched on race, maternal age, and birthweight. Conditional logistic regression analyses were performed. There were 116 cases and 232 controls studied. The incidence density of neonatal hypoglycemia was 24.7 per 1000 infant-days at risk. Hypoglycemia was less commonly associated with later gestational age (odds ratio [OR], 0.66; 95% confidence interval [CI], 0.53-0.85 per week of gestation). Maternal fever during labor was more common with hypoglycemia (OR, 4.08; 95% CI, 1.39-11.79). Public insurance was more than twice as common with hypoglycemia compared with those privately insured (OR, 2.31; 95% CI, 1.17-4.58). Neonatal hypoglycemia was associated with earlier gestational age, intrapartum fever, and public insurance.

Genetic polymorphisms for estimating risk of atrial fibrillation: a literature-based meta-analysis

PubMed Central

Smith, J. Gustav; Almgren, Peter; Engström, Gunnar; Hedblad, Bo; Platonov, Pyotr G.; Newton-Cheh, Christopher; Melander, Olle

2013-01-01

Objectives Genome-wide association studies have recently identified genetic polymorphisms associated with common, etiologically complex diseases, for which direct-to-consumer genetic testing with provision of absolute genetic risk estimates is marketed by commercial companies. Polymorphisms associated with atrial fibrillation (AF) have shown relatively large risk estimates but the robustness of such estimates across populations and study designs has not been studied. Design A systematic literature review with meta-analysis and assessment of between-study heterogeneity was performed for single nucleotide polymorphisms (SNPs) in the six genetic regions associated with AF in genome-wide or candidate gene studies. Results Data from 18 samples of European ancestry (n=12,100 cases; 115,702 controls) were identified for the SNP on chromosome 4q25 (rs220733), 16 samples (n=12,694 cases; 132,602 controls) for the SNP on 16q22 (rs2106261) and 4 samples (n=5,272 cases; 59,725 controls) for the SNP in KCNH2 (rs1805123). Only the discovery studies were identified for SNPs on 1q21 and in GJA5 and IL6R, why no meta-analyses were performed for those SNPs. In overall random-effects meta-analyses, association with AF was observed for both SNPs from genome-wide studies on 4q25 (OR 1.67, 95% CI=1.50–1.86, p=2×10−21) and 16q22 (OR 1.21, 95% CI=1.13–1.29, p=1×10−8), but not the SNP in KCNH2 from candidate gene studies (p=0.15). There was substantial effect heterogeneity across case-control and cross-sectional studies for both polymorphisms (I2=0.50–0.78, p<0.05), but not across prospective cohort studies (I2=0.39, p=0.15). Both polymorphisms were robustly associated with AF for each study design individually (p<0.05). Conclusions In meta-analyses including up to 150,000 individuals, polymorphisms in two genetic regions were robustly associated with AF across all study designs but with substantial context-dependency of risk estimates. PMID:22690879

Excessive work and risk of haemorrhagic stroke: a nationwide case-control study.

PubMed

Kim, Beom Joon; Lee, Seung-Hoon; Ryu, Wi-Sun; Kim, Chi Kyung; Chung, Jong-Won; Kim, Dohoung; Park, Hong-Kyun; Bae, Hee-Joon; Park, Byung-Joo; Yoon, Byung-Woo

2013-10-01

Adverse effect of excessive work on health has been suggested previously, but it was not documented in cerebrovascular diseases. The authors investigated whether excessive working conditions would associate with increased risk of haemorrhagic stroke. A nationwide matched case-control study database, which contains 940 cases of incident haemorrhagic stroke (498 intracerebral haemorrhages and 442 sub-arachnoid haemorrhages) with 1880 gender- and age- (± 5-year) matched controls, was analysed. Work-related information based on the regular job situation, including type of occupation, regular working time, duration of strenuous activity during regular work and shift work, was gathered through face-to-face interviews. Conditional logistic regression analyses were used for the multivariable analyses. Compared with white-collar workers, blue-collar workers had a higher risk for haemorrhagic stroke (odds ratio, 1.33 [95% confidence interval, 1.06-1.66]). Longer regular working time was associated with increased risk of haemorrhagic stroke [odds ratio, 1.38 (95% confidence interval, 1.05-1.81) for 8-12 h/day; odds ratio, 1.95 (95% confidence interval, 1.33-2.86) for ≥ 13 h/day; compared with ≤ 4 h/day]. Exposure to ≥ 8 h/week of strenuous activity also associated haemorrhagic stroke risk [odds ratio, 1.61 (95% confidence interval, 1.26-2.05); compared with no strenuous activity]. Shift work was not associated with haemorrhagic stroke (P = 0.98). Positive associations between working condition indices and haemorrhagic stroke risk were consistent regardless of haemorrhagic stroke sub-types and current employment status. Blue-collar occupation, longer regular working time and extended duration of strenuous activity during work may relate to an increased risk of haemorrhagic stroke. © 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.

Maternal fetal loss history and increased acute leukemia subtype risk in subsequent offspring: a systematic review and meta-analysis.

PubMed

Karalexi, M A; Dessypris, N; Skalkidou, A; Biniaris-Georgallis, S -I; Kalogirou, Ε Ι; Thomopoulos, T P; Herlenius, E; Spector, L G; Loutradis, D; Chrousos, G P; Petridou, E Th

2017-06-01

History of fetal loss including miscarriage and stillbirth has been inconsistently associated with childhood (0-14 years) leukemia in subsequent offspring. A quantitative synthesis of the inconclusive literature by leukemia subtype was therefore conducted. Eligible studies (N = 32) were identified through the screening of over 3500 publications. Random-effects meta-analyses were conducted on the association of miscarriage/stillbirth history with overall (AL; 18,868 cases/35,685 controls), acute lymphoblastic (ALL; 16,150 cases/38,655 controls), and myeloid (AML; 3042 cases/32,997 controls) leukemia. Sensitivity and subgroup analyses by age and ALL subtype, as well as meta-regression were undertaken. Fetal loss history was associated with increased AL risk [Odds Ratio (OR) 1.10, 95% Confidence Intervals (CI) 1.04-1.18]. The positive association was seen for ALL (OR 1.12, 95%CI 1.05-1.19) and for AML (OR 1.13, 95%CI 0.91-1.41); for the latter the OR increased in sensitivity analyses. Notably, stillbirth history was significantly linked to ALL risk (OR 1.33, 95%CI 1.02-1.74), but not AML. By contrast, the association of ALL and AML with previous miscarriage reached marginal significance. The association of miscarriage history was strongest in infant ALL (OR 2.34, 95%CI 1.19-4.60). In this meta-analysis involving >50,000 children, we found noteworthy associations by indices of fetal loss, age at diagnosis, and leukemia type; namely, of stillbirth with ALL and miscarriage history with infant ALL. Elucidation of plausible underlying mechanisms may provide insight into leukemia pathogenesis and indicate monitoring interventions prior to and during pregnancy.

Chronic beryllium disease and beryllium sensitization at Rocky Flats: a case-control study.

PubMed

Viet, S M; Torma-Krajewski, J; Rogers, J

2000-01-01

A case-control study was conducted to evaluate the risk of chronic beryllium disease (CBD) and beryllium sensitization (SENS) associated with various levels of historical beryllium exposure at the Rocky Flats nuclear weapons facility. Fifty CBD and 74 SENS cases were matched to controls of the same age group, race, gender, and smoking status. A job exposure matrix was developed from job history data and fixed airhead (FAH) exposure data available from 1960 to 1988. Job titles and building areas were assigned factors based on exposure relative to a machinist in the Building 444 Beryllium Shop. Concurrence on these factors was obtained from past and present Rocky Flats industrial hygienists. Using the matrix, long-term mean and cumulative exposures were estimated for each subject. Both exposure estimates (p < 0.0001) and years of employment (p = 0.010) were found to be significantly higher for CBD cases as compared with their controls, but not so for the SENS cases as compared with their controls. Logistic regression analyses showed statistically significant relationships between both cumulative and mean exposure and CBD, but not for SENS. These findings suggest that reduced worker exposures might lower the future incidence of CBD, but may not necessarily lower the incidence of SENS.

Seroprevalence of anti-Toxoplasma gondii and anti-Borrelia species antibodies in patients with schizophrenia: a case-control study from western Turkey.

PubMed

Cevizci, Sibel; Celik, Merve; Akcali, Alper; Oyekcin, Demet Gulec; Sahin, Ozlem Oztürk; Bakar, Coskun

2015-06-01

We examined IgG antibody seroprevalence and risk factors for anti-Toxoplasma gondii and anti-Borrelia sp. in schizophrenic patients. This case-control study included 30 schizophrenic patients and 60 healthy individuals. Serological analyses were identified by using ELISA technique. In the case group the Toxoplasma seropositivity was 33.3% and Borrelia seropositivity was 13.3%, while in the control group the Toxoplasma positivity was 21.7% and Borrelia seropositivity was 15.0%. There was no significant difference with regard to seroprevalence between the groups (P = 0.232; P = 0.832, respectively). There was statistically significant difference between case and control groups related to hand and kitchen utensil hygiene after dealing with raw meat (P = 0.001). Our data showed the rate of Toxoplasma antibodies was higher in the case group, while the rate of Borrelia antibodies was higher in the control group. In both groups the high rates of seropositivity for Toxoplasma gondii and Borrelia sp. is thought to be due to neglect of personal hygiene. The present study also is the first to examine the association between Borrelia sp. and schizophrenia. Further studies are needed to determine whether there is an association between Borrelia sp. and schizophrenia or not.

Listening panel agreement and characteristics of lung sounds digitally recorded from children aged 1–59 months enrolled in the Pneumonia Etiology Research for Child Health (PERCH) case–control study

PubMed Central

Park, Daniel E; Watson, Nora L; Buck, W Chris; Bunthi, Charatdao; Devendra, Akash; Ebruke, Bernard E; Elhilali, Mounya; Emmanouilidou, Dimitra; Garcia-Prats, Anthony J; Githinji, Leah; Hossain, Lokman; Madhi, Shabir A; Moore, David P; Mulindwa, Justin; Olson, Dan; Awori, Juliet O; Vandepitte, Warunee P; Verwey, Charl; West, James E; Knoll, Maria D; O'Brien, Katherine L; Feikin, Daniel R; Hammit, Laura L

2017-01-01

Introduction Paediatric lung sound recordings can be systematically assessed, but methodological feasibility and validity is unknown, especially from developing countries. We examined the performance of acoustically interpreting recorded paediatric lung sounds and compared sound characteristics between cases and controls. Methods Pneumonia Etiology Research for Child Health staff in six African and Asian sites recorded lung sounds with a digital stethoscope in cases and controls. Cases aged 1–59 months had WHO severe or very severe pneumonia; age-matched community controls did not. A listening panel assigned examination results of normal, crackle, wheeze, crackle and wheeze or uninterpretable, with adjudication of discordant interpretations. Classifications were recategorised into any crackle, any wheeze or abnormal (any crackle or wheeze) and primary listener agreement (first two listeners) was analysed among interpretable examinations using the prevalence-adjusted, bias-adjusted kappa (PABAK). We examined predictors of disagreement with logistic regression and compared case and control lung sounds with descriptive statistics. Results Primary listeners considered 89.5% of 792 case and 92.4% of 301 control recordings interpretable. Among interpretable recordings, listeners agreed on the presence or absence of any abnormality in 74.9% (PABAK 0.50) of cases and 69.8% (PABAK 0.40) of controls, presence/absence of crackles in 70.6% (PABAK 0.41) of cases and 82.4% (PABAK 0.65) of controls and presence/absence of wheeze in 72.6% (PABAK 0.45) of cases and 73.8% (PABAK 0.48) of controls. Controls, tachypnoea, >3 uninterpretable chest positions, crying, upper airway noises and study site predicted listener disagreement. Among all interpretable examinations, 38.0% of cases and 84.9% of controls were normal (p<0.0001); wheezing was the most common sound (49.9%) in cases. Conclusions Listening panel and case–control data suggests our methodology is feasible, likely valid and that small airway inflammation is common in WHO pneumonia. Digital auscultation may be an important future pneumonia diagnostic in developing countries. PMID:28883927

A HIV-1 heterosexual transmission chain in Guangzhou, China: a molecular epidemiological study.

PubMed

Han, Zhigang; Leung, Tommy W C; Zhao, Jinkou; Wang, Ming; Fan, Lirui; Li, Kai; Pang, Xinli; Liang, Zhenbo; Lim, Wilina W L; Xu, Huifang

2009-09-25

We conducted molecular analyses to confirm four clustering HIV-1 infections (Patient A, B, C & D) in Guangzhou, China. These cases were identified by epidemiological investigation and suspected to acquire the infection through a common heterosexual transmission chain. Env C2V3V4 region, gag p17/p24 junction and partial pol gene of HIV-1 genome from serum specimens of these infected cases were amplified by reverse transcription polymerase chain reaction (RT-PCR) and nucleotide sequenced. Phylogenetic analyses indicated that their viral nucleotide sequences were significantly clustered together (bootstrap value is 99%, 98% and 100% in env, gag and pol tree respectively). Evolutionary distance analysis indicated that their genetic diversities of env, gag and pol genes were significantly lower than non-clustered controls, as measured by unpaired t-test (env gene comparison: p < 0.005; gag gene comparison: p < 0.005; pol gene comparison: p < 0.005). Epidemiological results and molecular analyses consistently illustrated these four cases represented a transmission chain which dispersed in the locality through heterosexual contact involving commercial sex worker.

Risk factors for fibromyalgia: the role of violence against women.

PubMed

Ruiz-Pérez, Isabel; Plazaola-Castaño, Juncal; Cáliz-Cáliz, Rafael; Rodríguez-Calvo, Isabel; García-Sánchez, Antonio; Ferrer-González, Miguel Angel; Guzmán-Ubeda, Manuel; del Río-Lozano, María; López-Chicheri García, Isabel

2009-07-01

The objectives of the study were to analyse the association between fibromyalgia (FM) and violence against women and to explore the association between FM and sociodemographic factors, social support and psychological distress. A case-control study was conducted in a Spanish hospital. Cases were women diagnosed with FM, with no signs of any other type of inflammatory rheumatic disorder, who were seen at the Rheumatology Department of the hospital. Controls were women not diagnosed with FM who were seen at the Ear, Nose and Throat Department of the same hospital. A self-administered anonymous questionnaire was used to gather data on sociodemographic characteristics, violence, social support and psychological distress. Uni-, bi- and multivariate logistic regression analyses were conducted; 287 cases and 287 controls were recruited. The multivariate analysis showed that the probability of presenting FM increased with age (odds ratios (OR) = 1.06; CI95% = 1.03-1.09); that employed women and housewives were more likely to have the syndrome than unemployed women or students (OR = 4.97; CI95% = 1.45-17.02, and OR = 3.47; CI95% = 0.98-12.22, respectively); that the lower the educational level, the higher the probability of having FM; and that psychological distress was positively associated with the syndrome (OR = 4.62; CI95% = 2.68-7.97). Although abuse was more prevalent in cases than in controls, the differences were not statistically significant. However, frequency of abuse was positively and significantly correlated with FM. Although the aetiology of FM is still uncertain, it seems that certain psychosocial factors may be associated with the syndrome. Therefore, an interdisciplinary approach to the treatment of patients affected with this syndrome should be considered.

Association between periodontitis and ischemic stroke: a systematic review and meta-analysis.

PubMed

Leira, Yago; Seoane, Juan; Blanco, Miguel; Rodríguez-Yáñez, Manuel; Takkouche, Bahi; Blanco, Juan; Castillo, José

2017-01-01

Several observational studies have suggested an association between periodontitis and cerebral ischemia. This meta-analysis aimed to investigate whether this link exists, and if so, the degree to which it is significant. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline for systematic review was used. The search strategy included using electronic databases and hand searching works published up to March 2015. MEDLINE via PubMed, EMBASE, Proceedings Web of Science and Current Contents Connect were searched by two independent reviewers. Case-control, cross-sectional or cohort studies including patients with measures of periodontitis and ischemic stroke were eligible to be included in the analysis. Quality assessments of selected studies were performed. From a total of 414 titles and abstracts, 57 potentially relevant full text papers were identified. After inclusion criteria were applied, 8 studies were included in the present systematic review (5 case-control and 3 cohort studies). Although it was not the intention, cross-sectional studies were excluded due to eligibility criteria were not accomplished. Therefore, meta-analyses were conducted with data retrieved from the 8 studies included. These meta-analyses showed statistically significant association between periodontitis and ischemic stroke in both cohort pooled relative risks at 2.52 (1.77-3.58), and case-control studies pooled relative risks at 3.04 (1.10-8.43). In conclusion, the present meta-analysis demonstrated an association between periodontitis and ischemic stroke. However, well-designed prospective studies should be carried out to provide robust evidence of the link between both diseases. In regards to ischemic stroke subtypes, further case-control studies should be carried out to investigate whether there is any association between the different subtypes of cerebral infarcts and periodontitis.

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.

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.

Does low to moderate environmental exposure to noise and air pollution influence preterm delivery in medium-sized cities?

PubMed

Barba-Vasseur, Marie; Bernard, Nadine; Pujol, Sophie; Sagot, Paul; Riethmuller, Didier; Thiriez, Gérard; Houot, Hélène; Defrance, Jérôme; Mariet, Anne-Sophie; Luu, Vinh-Phuc; Barbier, Alice; Benzenine, Eric; Quantin, Catherine; Mauny, Frédéric

2017-12-01

Preterm birth (PB) is an important predictor of childhood morbidity and educational performance. Beyond the known risk factors, environmental factors, such as air pollution and noise, have been implicated in PB. In urban areas, these pollutants coexist. Very few studies have examined the effects of multi-exposure on the pregnancy duration. The objective of this study was to analyse the relationship between PB and environmental chronic multi-exposure to noise and air pollution in medium-sized cities. A case-control study was conducted among women living in the city of Besançon (121 671 inhabitants) or in the urban unit of Dijon (243 936 inhabitants) and who delivered in a university hospital between 2005 and 2009. Only singleton pregnancies without associated pathologies were considered. Four controls were matched to each case in terms of the mother's age and delivery location. Residential noise and nitrogen dioxide (NO2) exposures were calculated at the mother's address. Conditional logistic regression models were applied, and sensitivity analyses were performed. This study included 302 cases and 1204 controls. The correlation between noise and NO2 indices ranged from 0.41 to 0.59. No significant differences were found in pollutant exposure levels between cases and controls. The adjusted odds ratios ranged between 0.96 and 1.08. Sensitivity analysis conducted using different temporal and spatial exposure windows demonstrated the same results. The results are in favour of a lack of connection between preterm delivery and multi-exposure to noise and air pollution in medium-sized cities for pregnant women without underlying disease. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Dientamoeba fragilis colonization is not associated with gastrointestinal symptoms in children at primary care level.

PubMed

Holtman, Gea A; Kranenberg, Justin J; Blanker, Marco H; Ott, Alewijn; Lisman-van Leeuwen, Yvonne; Berger, Marjolein Y

2017-02-01

Dientamoeba fragilis is commonly identified in children in primary care and is suspected to cause gastrointestinal disease. To determine the association between D. fragilis colonization and gastrointestinal symptoms in children. We performed a cross-sectional study with children who presented in primary care with gastrointestinal symptoms. The associations between D. fragilis colonization and specific symptoms were explored by means of logistic regression analyses. Asymptomatic siblings of these cases were invited as control subjects for a case-control analysis, where we explored the association between D. fragilis and gastrointestinal symptoms with conditional logistic regression analysis. In the cross-sectional study, 107 children were included. Their median age was 9 years (interquartile range = 6-12) and 38 (35.5%) were boys. Colonization of D. fragilis was present in 59 children (55.1%). The absence of D. fragilis was associated with soft to watery stool [odds ratio (OR) = 0.29; 95% confidence interval (CI) = 0.10-0.85], chronic diarrhoea (OR = 0.42; 95% CI = 0.18-0.97) and fatigue (OR = 0.45; 95% CI = 0.20-0.99). The case-control analyses included 44 children in each group. Dientamoeba fragilis colonization was not observed more often in cases than in controls after adjustment for age and sex (OR = 1.02; 95% CI = 0.28-3.65). Dientamoeba fragilis is a common parasite in children with and without gastrointestinal symptoms. The anomalous finding of the association between the absence of D. fragilis with soft to watery stools, chronic diarrhoea and fatigue are inexplicable. Our study suggests that D. fragilis colonization does not increase the risk for gastrointestinal symptoms. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Elevated Brain Harmane (1-methyl-9H-pyrido[3,4-b]indole) in Essential Tremor Cases vs. Controls

PubMed Central

Louis, Elan D.; Factor-Litvak, Pam; Liu, Xinhua; Vonsattel, Jean-Paul G.; Galecki, Monika; Jiang, Wendy; Zheng, Wei

2013-01-01

Background Harmane (1-methyl-9H-pyrido[3,4-β]indole), a potent neurotoxin that has tremor-producing properties in animal models, is present in many foods; Although we have demonstrated a difference in tissue harmane concentrations in ET cases vs. controls, all work to date has involved blood samples. Objectives We quantified harmane concentrations in human cerebellum, a brain region of particular pathogenic interest in essential tremor (ET), comparing ET to control brains. Methods Cerebellar cortex was snap frozen and stored at -80ºC in aliquots for biochemical analyses. Harmane concentration was assessed using high performance liquid chromatography. Results Geometric mean brain harmane concentrations (adjusted for postmortem interval [PMI] and freezer time) were higher in ET cases than controls: 1.0824 (95% confidence interval = 0.9405 – 1.2457) vs. 0.8037 (0.6967 – 0.9272), p = 0.004. Geometric mean of brain harmane concentrations (adjusting for PMI and freezer time) was highest in ET cases who reported other relatives with tremor (1.2005 [0.8712 – 1.6541]), intermediate in ET cases without family history (1.0312 ([0.8879 – 1.1976]), and both were significantly higher than controls (p= 0.02). Conclusions This study provides additional evidence of a possible etiological importance of this toxin in some cases of the human disease ET. PMID:23911942

Elevated brain harmane (1-methyl-9H-pyrido[3,4-b]indole) in essential tremor cases vs. controls.

PubMed

Louis, Elan D; Factor-Litvak, Pam; Liu, Xinhua; Vonsattel, Jean-Paul G; Galecki, Monika; Jiang, Wendy; Zheng, Wei

2013-09-01

Harmane (1-methyl-9H-pyrido[3,4-β]indole), a potent neurotoxin that has tremor-producing properties in animal models, is present in many foods; although we have demonstrated a difference in tissue harmane concentrations in ET cases vs. controls, all work to date has involved blood samples. We quantified harmane concentrations in human cerebellum, a brain region of particular pathogenic interest in essential tremor (ET), comparing ET to control brains. Cerebellar cortex was snap frozen and stored at -80°C in aliquots for biochemical analyses. Harmane concentration was assessed using high performance liquid chromatography. Geometric mean brain harmane concentrations (adjusted for postmortem interval [PMI] and freezer time) were higher in ET cases than controls: 1.0824 (95% confidence interval=0.9405-1.2457) vs. 0.8037 (0.6967-0.9272), p=0.004. Geometric mean of brain harmane concentrations (adjusting for PMI and freezer time) was highest in ET cases who reported other relatives with tremor (1.2005 [0.8712-1.6541]), intermediate in ET cases without family history (1.0312 ([0.8879-1.1976]), and both were significantly higher than controls (p=0.02). This study provides additional evidence of a possible etiological importance of this toxin in some cases of the human disease ET. Copyright © 2013 Elsevier Inc. All rights reserved.

Dietary habits after myocardial infarction - results from a cross-sectional study.

PubMed

Wallström, P; Mattisson, I; Tydén, P; Berglund, G; Janzon, L

2005-04-01

Comparing habitual nutrient intakes in persons with a history of acute myocardial infarction (AMI), and age-matched controls. Design. Cross-sectional study. Subjects. Men and women (525 cases and 1890 matched controls), aged 47-73 years, of the population-based Malmö Diet and Cancer cohort. Nutrient intakes were assessed by a validated modified diet history method. Body fatness was assessed by bioimpedance analysis. Case ascertainment was provided by national and regional registries. Men and women were analysed separately. Median time since AMI was 5.5 years in men and 3.8 years in women. Cases reported lower energy intakes (EIs) than controls, despite having similar basal metabolic rates. After adjustment for total EI, both male and female cases had lower fat intake and higher intake of several micronutrients, such as ascorbic acid, folate, and vitamin E, than controls, the difference being largest in men. Most of the cases reporting dietary change quoted 'disease' as their main reason for change. They had lower EI and lower energy-adjusted intake of fat than other cases. Survivors of AMI reported dietary habits more in line with current recommendations, particularly those who afterwards reported having changed their dietary habits. The possible bias introduced by social desirability is discussed.

Culture, risk factors and suicide in rural China: a psychological autopsy case control study.

PubMed

Zhang, J; Conwell, Y; Zhou, L; Jiang, C

2004-12-01

Previous research on sociocultural factors for Chinese suicide have been basically limited to single case studies or qualitative research with ethnographic methodology. The current study examines the major risk factors and some cultural uniqueness related to Chinese rural suicide using a quantitative design. This is a case control study with 66 completed suicides and 66 living controls obtained from psychological autopsy interviews in rural China. Both bivariate analyses and the multiple regression model have found that the Chinese rural suicide patterns are basically similar to those in most other cultures in the world: strong predictors of rural Chinese suicide are the psychopathological, psychological, and physical health variables, followed by social support and negative and stressful life events. Other significant correlates include lower education, poverty, religion, and family disputes. Culture has an important impact on suicide patterns in a society.

Culture, risk factors and suicide in rural China: a psychological autopsy case control study

PubMed Central

Zhang, J.; Conwell, Y.; Zhou, L.; Jiang, C.

2009-01-01

Objective Previous research on sociocultural factors for Chinese suicide have been basically limited to single case studies or qualitative research with ethnographic methodology. The current study examines the major risk factors and some cultural uniqueness related to Chinese rural suicide using a quantitative design. Method This is a case control study with 66 completed suicides and 66 living controls obtained from psychological autopsy interviews in rural China. Results Both bivariate analyses and the multiple regression model have found that the Chinese rural suicide patterns are basically similar to those in most other cultures in the world: strong predictors of rural Chinese suicide are the psychopathological, psychological, and physical health variables, followed by social support and negative and stressful life events. Other significant correlates include lower education, poverty, religion, and family disputes. Conclusion Culture has an important impact on suicide patterns in a society. PMID:15521827

Erythrocyte Membrane Fatty Acid Composition in Premenopausal Patients with Iron Deficiency Anemia.

PubMed

Aktas, Mehmet; Elmastas, Mahfuz; Ozcicek, Fatih; Yilmaz, Necmettin

2016-01-01

Iron deficiency anemia (IDA) is one of the most common nutritional disorders in the world. In the present study, we evaluated erythrocyte membrane fatty acid composition in premenopausal patients with IDA. Blood samples of 102 premenopausal women and 88 healthy control subjects were collected. After the erythrocytes were separated from the blood samples, the membrane lipids were carefully extracted, and the various membrane fatty acids were measured by gas chromatography (GC). Statistical analyses were performed with the SPSS software program. We used blood ferritin concentration <15 ng/mL as cut-off for the diagnosis of IDA. The five most abundant individual fatty acids obtained were palmitic acid (16:0), oleic acid (18:1, n-9c), linoleic acid (18:2, n-6c), stearic acid (18:0), and erucic acid (C22:1, n-9c). These compounds constituted about 87% of the total membrane fatty acids in patients with IDA, and 79% of the total membrane fatty acids in the control group. Compared with control subjects, case patients had higher percentages of palmitic acid (29.9% case versus 25.3% control), oleic acid (16.8% case versus 15.1% control), and stearic acid (13.5% case versus 10.5% control), and lower percentages of erucic acid (11.5% case versus 13.6% control) and linoleic acid (15.2% case versus 15.4% control) in their erythrocyte membranes. In conclusion, the total-erythrocyte-membrane saturated fatty acid (SFA) composition in premenopausal women with IDA was found to be higher than that in the control group; however, the total-erythrocyte-membrane unsaturated fatty acid (UFA) composition in premenopausal women with IDA was found to be lower than that in the control group. The differences in these values were statistically significant.

[Evaluation of the organization of health services as a strategy for the prevention and control of visceral leishmaniasis].

PubMed

Barbosa, Miriam Nogueira; Guimarães, Eliete Albano de Azevedo; Luz, Zélia Maria Profeta da

2016-01-01

to evaluate the organization of health services as a strategy for the prevention and control of visceral leishmaniasis (VL) in Ribeirão das Neves, Minas Gerais, Brazil, from 2010 to 2012. this was a case study evaluation of the degree of implementation of a strategy for the integration of health care services, control of zoonosis and epidemiological surveillance; it consisted of observing the work process, interviewing health professionals and analysing secondary data from information systems. implementation was partially adequate (84%); in terms of structure, the human resources component had the worst evaluation (64%) whilst in terms of work process, evaluation was 80% for reorganization of care and 77% for surveillance; in the period 2010-2012 there was a 20% increase in reported cases of VL and a 20% reduction in the time interval between reporting a case and starting treatment. the strategy contributed to the improvement of the organization of VL prevention and control actions.

Oral health status of women with high-risk pregnancies.

PubMed

Merglova, Vlasta; Hecova, Hana; Stehlikova, Jaroslava; Chaloupka, Pavel

2012-12-01

The aim of this study was to investigate the oral health status of women with high-risk pregnancies. A case-control study of 142 pregnant women was conducted. The case group included 81 pregnant women with high-risk pregnancies, while 61 women with normal pregnancies served as controls. The following variables were recorded for each woman: age, general health status, DMF, CPITN, and PBI index, amounts of Streptococcus mutans in the saliva and dental treatment needs. The Mann-Whitney test, Kruskal-Wallis test, t-test and chi-squared test were used for statistical analyses. Statistically significant differences were detected between the PBI indices and dental treatment needs of the two groups. Out of the entire study cohort, 77% of the women in the case group and 52% of the women in the control group required dental treatment. In this study, women with complications during pregnancy had severe gingivitis and needed more frequent dental treatment than those in the control group.

Case−Control Study of Risk Factors for Meningococcal Disease in Chile

PubMed Central

Matute, Isabel; González, Claudia; Delgado, Iris; Poffald, Lucy; Pedroni, Elena; Alfaro, Tania; Hirmas, Macarena; Nájera, Manuel; Gormaz, Ana; López, Darío; Loayza, Sergio; Ferreccio, Catterina; Gallegos, Doris; Fuentes, Rodrigo; Vial, Pablo; Aguilera, Ximena

2017-01-01

An outbreak of meningococcal disease with a case-fatality rate of 30% and caused by predominantly serogroup W of Neisseria meningitidis began in Chile in 2012. This outbreak required a case−control study to assess determinants and risk factors for infection. We identified confirmed cases during January 2012−March 2013 and selected controls by random sampling of the population, matched for age and sex, resulting in 135 case-patients and 618 controls. Sociodemographic variables, habits, and previous illnesses were studied. Analyses yielded adjusted odds ratios as estimators of the probability of disease development. Results indicated that conditions of social vulnerability, such as low income and overcrowding, as well as familial history of this disease and clinical histories, especially chronic diseases and hospitalization for respiratory conditions, increased the probability of illness. Findings should contribute to direction of intersectoral public policies toward a highly vulnerable social group to enable them to improve their living conditions and health. PMID:28628448

Optimisation of active suspension control inputs for improved vehicle ride performance

NASA Astrophysics Data System (ADS)

Čorić, Mirko; Deur, Joško; Xu, Li; Tseng, H. Eric; Hrovat, Davor

2016-07-01

A collocation-type control variable optimisation method is used in the paper to analyse to which extent the fully active suspension (FAS) can improve the vehicle ride comfort while preserving the wheel holding ability. The method is first applied for a cosine-shaped bump road disturbance of different heights, and for both quarter-car and full 10 degree-of-freedom vehicle models. A nonlinear anti-wheel hop constraint is considered, and the influence of bump preview time period is analysed. The analysis is then extended to the case of square- or cosine-shaped pothole with different lengths, and the quarter-car model. In this case, the cost function is extended with FAS energy consumption and wheel damage resilience costs. The FAS action is found to be such to provide a wheel hop over the pothole, in order to avoid or minimise the damage at the pothole trailing edge. In the case of long pothole, when the FAS cannot provide the wheel hop, the wheel is travelling over the pothole bottom and then hops over the pothole trailing edge. The numerical optimisation results are accompanied by a simplified algebraic analysis.

Geographic profiling as a novel spatial tool for targeting infectious disease control.

PubMed

Le Comber, Steven C; Rossmo, D Kim; Hassan, Ali N; Fuller, Douglas O; Beier, John C

2011-05-18

Geographic profiling is a statistical tool originally developed in criminology to prioritise large lists of suspects in cases of serial crime. Here, we use two data sets--one historical and one modern--to show how it can be used to locate the sources of infectious disease. First, we re-analyse data from a classic epidemiological study, the 1854 London cholera outbreak. Using 321 disease sites as input, we evaluate the locations of 13 neighbourhood water pumps. The Broad Street pump--the outbreak's source--ranks first, situated in the top 0.2% of the geoprofile. We extend our study with an analysis of reported malaria cases in Cairo, Egypt, using 139 disease case locations to rank 59 mosquitogenic local water sources, seven of which tested positive for the vector Anopheles sergentii. Geographic profiling ranks six of these seven sites in positions 1-6, all in the top 2% of the geoprofile. In both analyses the method outperformed other measures of spatial central tendency. We suggest that geographic profiling could form a useful component of integrated control strategies relating to a wide variety of infectious diseases, since evidence-based targeting of interventions is more efficient, environmentally friendly and cost-effective than untargeted intervention.

Acute nonlymphocytic leukemia and residential exposure to power frequency magnetic fields

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

Severson, R.K.

1986-01-01

A population-based case-control study of adult acute nonlymphocytic leukemia (ANLL) and residential exposure to power frequency magnetic fields was conducted in King, Pierce and Snohomish Counties in Washington state. Of 164 cases who were diagnosed from January 1, 1981 through December 31, 1984, 114 were interviewed. Controls were selected from the study area on the basis of random digit dialing and frequency matched to the cases by age and sex. Analyses were undertaken to evaluate whether exposure to high levels of power frequency magnetic fields in the residence were associated with an increased risk of ANLL. Neither the directly measuredmore » magnetic fields nor the surrogate values based on the wiring configurations were associated with ANLL. Additional analyses suggested that persons with prior allergies were at decreased risk of acute myelocytic leukemia (AML). Also, persons with prior autoimmune diseases were at increased risk of AML. The increase in AML risk in rheumatoid arthritics was of borderline statistical significance. Finally, cigarette smoking was associated with an increased risk of AML. The risk of AML increased significantly with the number of years of cigarette smoking.« less

Association of common polymorphisms in GLUT9 gene with gout but not with coronary artery disease in a large case-control study.

PubMed

Stark, Klaus; Reinhard, Wibke; Neureuther, Katharina; Wiedmann, Silke; Sedlacek, Kamil; Baessler, Andrea; Fischer, Marcus; Weber, Stefan; Kaess, Bernhard; Erdmann, Jeanette; Schunkert, Heribert; Hengstenberg, Christian

2008-04-09

Serum uric acid (UA) levels have recently been shown to be genetically influenced by common polymorphisms in the GLUT9 gene in two genome-wide association analyses of Italian and British populations. Elevated serum UA levels are often found in conjunction with the metabolic syndrome. Hyperuricemia is the major risk factor for gout and has been associated with increased cardiovascular morbidity and mortality. The aim of the present study was to further elucidate the association of polymorphisms in GLUT9 with gout and coronary artery disease (CAD) or myocardial infarction (MI). To test our hypotheses, we performed two large case-control association analyses of individuals from the German MI Family Study. First, 665 patients with gout and 665 healthy controls, which were carefully matched for age and gender, were genotyped for four single nucleotide polymorphisms (SNPs) within or near the GLUT9 gene. All four SNPs demonstrated highly significant association with gout. SNP rs6855911, located within intron 7 of GLUT9, showed the strongest signal with a protective effect of the minor allele with an allelic odds ratio of 0.62 (95% confidence interval 0.52-0.75; p = 3.2*10(-7)). Importantly, this finding was not influenced by adjustment for components of the metabolic syndrome or intake of diuretics. Secondly, 1,473 cases with severe CAD or MI and 1,241 healthy controls were tested for the same four GLUT9 SNPs. The analyses revealed, however, no significant association with CAD or with MI. Additional screening of genome-wide association data sets showed no signal for CAD or MI within the GLUT9 gene region. Thus, our results provide compelling evidence that common genetic variations within the GLUT9 gene strongly influence the risk for gout but are unlikely to have a major effect on CAD or MI in a German population.

Cost-effectiveness of adding indoor residual spraying to case management in Afghan refugee settlements in Northwest Pakistan during a prolonged malaria epidemic.

PubMed

Howard, Natasha; Guinness, Lorna; Rowland, Mark; Durrani, Naeem; Hansen, Kristian S

2017-10-01

Financing of malaria control for displaced populations is limited in scope and duration, making cost-effectiveness analyses relevant but difficult. This study analyses cost-effectiveness of adding prevention through targeted indoor residual spraying (IRS) to case management in Afghan refugee settlements in Pakistan during a prolonged malaria epidemic. An intervention study design was selected, taking a societal perspective. Provider and household costs of vector control and case management were collected from provider records and community survey. Health outcomes (e.g. cases and DALYs averted) were derived and incremental cost-effectiveness ratios (ICERs) for cases prevented and DALYs averted calculated. Population, treatment cost, women's time, days of productivity lost, case fatality rate, cases prevented, and DALY assumptions were tested in sensitivity analysis. Malaria incidence peaked at 44/1,000 population in year 2, declining to 14/1,000 in year 5. In total, 370,000 malaria cases, 80% vivax, were diagnosed and treated and an estimated 67,988 vivax cases and 18,578 falciparum and mixed cases prevented. Mean annual programme cost per capita was US$0.56. The additional cost of including IRS over five years per case prevented was US$39; US$50 for vivax (US$43 in years 1-3, US$80 in years 4-5) and US$182 for falciparum (US$139 in years 1-3 and US$680 in years 4-5). Per DALY averted this was US$266 (US$220 in years 1-3 and US$486 in years 4-5) and thus 'highly cost-effective' or cost-effective using WHO and comparison thresholds. Adding IRS was cost-effective in this moderate endemicity, low mortality setting. It was more cost-effective when transmission was highest, becoming less so as transmission reduced. Because vivax was three times more common than falciparum and the case fatality rate was low, cost-effectiveness estimations for cases prevented appear reliable and more definitive for vivax malaria.

Measures to control an imported case of canine rabies in France.

PubMed

2006-01-01

France has been free from terrestrial rabies since 2001. On 21 August 2004, a female dog aged 4 months died in Gironde (south-west France), after experiencing clinical symptoms suggestive of rabies for 3 days. On 26 August, a diagnosis of rabies was confirmed by the Pasteur Institute. This paper describes the measures that were taken to manage the risks to human and animal health, and analyses the alert raised in France as a result of this imported case of rabies, the third such case in 2004.

Risk factors for microbial bioburden during daily wear of silicone hydrogel contact lenses.

PubMed

Jiang, Ying; Jacobs, Michael; Bajaksouzian, Saralee; Foster, Altreisha N; Debanne, Sara M; Bielefeld, Roger; Garvey, Matt; Raghupathy, Sangeetha; Kern, Jami; Szczotka-Flynn, Loretta B

2014-05-01

To assess risk factors associated with substantial microbial bioburden of lids, conjunctivae, contact lenses, and storage cases during daily wear of silicone hydrogel contact lenses. Two hundred eighteen patients were fit to lotrafilcon A lenses, randomized to use either a multipurpose solution or a hydrogen peroxide care system, and followed up for 1 year. Lenses, lens transport saline, lids, conjunctivae, and storage cases were cultured and considered to have substantial microbial bioburden when they harbored high levels of commensal or pathogenic organisms. Univariate and multivariate logistic regression analyses were conducted to examine which demographic covariates were associated with significant bioburden at each location while controlling for solution use. In multivariate analyses, smoking trended toward an association with lens bioburden (odds ratio [OR]=2.15, 95% confidence interval [CI]: 0.95-4.88). Clerical occupations were found to be associated with more frequent overall storage case contamination (OR=3.51, 95% CI: 1.15-10.70) and, specifically, higher gram-positive storage case contamination (OR=5.57, 95% CI: 1.82-17.06). The peroxide system was associated with more frequent storage case contamination (OR=7.6, 95% CI: 3.79-15.19). Coagulase-negative staphylococci (CNS) were the most frequently cultured organisms within storage cases, and in multivariate analyses, CNS were more frequently found in storage cases of peroxide users (OR=6.12, 95% CI: 2.91-13.09). Clerical occupations were associated with increased microbial bioburden of storage cases during daily wear of silicone hydrogel lenses. Smoking may increase the risk of lens contamination. Storage cases are most frequently contaminated with normal skin flora, and peroxide cases were associated with more frequent contamination. However, the solution type was not associated with lid or lens contamination nor with corneal infiltrative events in this study.

Case Study: Influences of Uncertainties and Traffic Scenario Difficulties in a Human-in-the-Loop Simulation

NASA Technical Reports Server (NTRS)

Bienert, Nancy; Mercer, Joey; Homola, Jeffrey; Morey, Susan; Prevot, Thomas

2014-01-01

This paper presents a case study of how factors such as wind prediction errors and metering delays can influence controller performance and workload in Human-In-The-Loop simulations. Retired air traffic controllers worked two arrival sectors adjacent to the terminal area. The main tasks were to provide safe air traffic operations and deliver the aircraft to the metering fix within +/- 25 seconds of the scheduled arrival time with the help of provided decision support tools. Analyses explore the potential impact of metering delays and system uncertainties on controller workload and performance. The results suggest that trajectory prediction uncertainties impact safety performance, while metering fix accuracy and workload appear subject to the scenario difficulty.

Assimilation of Quality Controlled AIRS Temperature Profiles using the NCEP GFS

NASA Technical Reports Server (NTRS)

Susskind, Joel; Reale, Oreste; Iredell, Lena; Rosenberg, Robert

2013-01-01

We have previously conducted a number of data assimilation experiments using AIRS Version-5 quality controlled temperature profiles as a step toward finding an optimum balance of spatial coverage and sounding accuracy with regard to improving forecast skill. The data assimilation and forecast system we used was the Goddard Earth Observing System Model , Version-5 (GEOS-5) Data Assimilation System (DAS), which represents a combination of the NASA GEOS-5 forecast model with the National Centers for Environmental Prediction (NCEP) operational Grid Point Statistical Interpolation (GSI) global analysis scheme. All analyses and forecasts were run at a 0.5deg x 0.625deg spatial resolution. Data assimilation experiments were conducted in four different seasons, each in a different year. Three different sets of data assimilation experiments were run during each time period: Control; AIRS T(p); and AIRS Radiance. In the "Control" analysis, all the data used operationally by NCEP was assimilated, but no AIRS data was assimilated. Radiances from the Aqua AMSU-A instrument were also assimilated operationally by NCEP and are included in the "Control". The AIRS Radiance assimilation adds AIRS observed radiance observations for a select set of channels to the data set being assimilated, as done operationally by NCEP. In the AIRS T(p) assimilation, all information used in the Control was assimilated as well as Quality Controlled AIRS Version-5 temperature profiles, i.e., AIRS T(p) information was substituted for AIRS radiance information. The AIRS Version-5 temperature profiles were presented to the GSI analysis as rawinsonde profiles, assimilated down to a case-by-case appropriate pressure level p(sub best) determined using the Quality Control procedure. Version-5 also determines case-by-case, level-by-level error estimates of the temperature profiles, which were used as the uncertainty of each temperature measurement. These experiments using GEOS-5 have shown that forecasts resulting from analyses using the AIRS T(p) assimilation system were superior to those from the Radiance assimilation system, both with regard to global 7 day forecast skill and also the ability to predict storm tracks and intensity.

Vitamins and abdominal aortic aneurysm.

PubMed

Takagi, Hisato; Umemoto, Takuya

2017-02-01

To summarize the association of vitamins (B6, B12, C, D, and E) and abdominal aortic aneurysm (AAA), we reviewed clinical studies with a comprehensive literature research and meta-analytic estimates. To identify all clinical studies evaluating the association of vitamins B6/B12/C/D/E and AAA, databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through April 2015, using Web-based search engines (PubMed and OVID). For each case-control study, data regarding vitamin levels in both the AAA and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Pooled analyses of the 4 case-control studies demonstrated significantly lower circulating vitamin B6 levels (SMD, -0.33; 95% CI, -0.55 to -0.11; P=0.003) but non-significantly lower vitamin B12 levels (SMD, -0.42; 95% CI, -1.09 to 0.25; P=0.22) in patients with AAA than subjects without AAA. Pooled analyses of the 2 case-control studies demonstrated significantly lower levels of circulating vitamins C (SMD, -0.71; 95% CI, -1.23 to -0.19; P=0.007) and E (SMD, -1.76; 95% CI, -2.93 to 0.60; P=0.003) in patients with AAA than subjects without AAA. Another pooled analysis of the 3 case-control studies demonstrated significantly lower circulating vitamin D (25-hydroxyvitamin D) levels (SMD, -0.25; 95% CI, -0.50 to -0.01; P=0.04) in patients with AAA than subjects without AAA. In a double-blind controlled trial, 4.0-year treatment with a high-dose folic acid and vitamin B6/B12 multivitamin in kidney transplant recipients did not reduce a rate of AAA repair despite significant reduction in homocysteine level. In another randomized, double-blind, placebo-controlled trial, 5.8-year supplementation with α-tocopherol (vitamin E) had no preventive effect on large AAA among male smokers. In clinical setting, although low circulating vitamins B6/C/D/E (not B12) levels are associated with AAA presence, vitamins B6/B12/E supplementation may not reduce AAA incidence.

Malaria Risk Factors in Kaligesing, Purworejo District, Central Java Province, Indonesia: A Case-control Study.

PubMed

Cahyaningrum, Pratiwi; Sulistyawati, Sulistyawati

2018-05-01

Malaria remains a public health concern worldwide, including Indonesia. Purworejo is a district in which endemic of malaria, they have re-setup to entering malaria elimination in 2021. Accordingly, actions must be taken to accelerate and guaranty that the goal will reach based on an understanding of the risk factors for malaria. Thus, we analysed malaria risk factors based on human and housing conditions in Kaligesing, Purworejo, Indonesia. A case-control study was carried out in Kaligesing subdistrict, Purworejo, Indonesia in July to August 2017. A structured questionnaire and checklist were used to collect data from 96 participants, who consisted of 48 controls and 48 cases. Univariate, bivariate, and multivariate analyses were performed. Bivariate analysis found that education level, the presence of a cattle cage within 100 m of the house, not sleeping under a bednet the previous night, and not closing the doors and windows from 6 p.m. to 5 a.m. were significantly ( p ≤0.25) associated with malaria. Of these factors, only not sleeping under a bednet the previous night and not closing the doors and windows from 6 p.m. to 5 a.m. were significantly associated with malaria. The findings of this study demonstrate that potential risk factor for Malaria should be paid of attention all the time, particularly for an area which is targeting Malaria elimination.

Employment, working conditions, and preterm birth: results from the Europop case-control survey.

PubMed

Saurel-Cubizolles, M J; Zeitlin, J; Lelong, N; Papiernik, E; Di Renzo, G C; Bréart, G

2004-05-01

To analyse the relation between preterm birth and working conditions in Europe using common measures of exposure and to test whether employment related risks varied by country of residence. A case-control study in which cases included all consecutive singleton preterm births and controls included one of every ten singleton term births in each participating maternity unit. Data about working conditions were obtained by interview from women after delivery. Sixteen European countries. The analysis included 5145 preterm and 7911 term births of which 2369 preterm and 4098 term births were to women employed during pregnancy. Analyses of working conditions were carried out for women working through at least the third month of pregnancy. Employed women did not have an excess risk of preterm birth. Among working women, a moderate excess risk was observed for women working more than 42 hours a week (OR = 1.33, CI = 1.1 to 1.6), standing more than six hours a day (OR = 1.26, CI = 1.1 to 1.5), and for women with low job satisfaction (OR = 1.27, CI = 1.1 to 1.5). There were stronger links in countries with a lower overall level of perinatal health and a common practice of long prenatal leaves. These findings show that specific working conditions affect the risk of preterm birth. They also suggest employment related risks could be mediated by the social and legislative context.

Bridging ImmunoGenomic Data Analysis Workflow Gaps (BIGDAWG): An integrated case-control analysis pipeline.

PubMed

Pappas, Derek J; Marin, Wesley; Hollenbach, Jill A; Mack, Steven J

2016-03-01

Bridging ImmunoGenomic Data-Analysis Workflow Gaps (BIGDAWG) is an integrated data-analysis pipeline designed for the standardized analysis of highly-polymorphic genetic data, specifically for the HLA and KIR genetic systems. Most modern genetic analysis programs are designed for the analysis of single nucleotide polymorphisms, but the highly polymorphic nature of HLA and KIR data require specialized methods of data analysis. BIGDAWG performs case-control data analyses of highly polymorphic genotype data characteristic of the HLA and KIR loci. BIGDAWG performs tests for Hardy-Weinberg equilibrium, calculates allele frequencies and bins low-frequency alleles for k×2 and 2×2 chi-squared tests, and calculates odds ratios, confidence intervals and p-values for each allele. When multi-locus genotype data are available, BIGDAWG estimates user-specified haplotypes and performs the same binning and statistical calculations for each haplotype. For the HLA loci, BIGDAWG performs the same analyses at the individual amino-acid level. Finally, BIGDAWG generates figures and tables for each of these comparisons. BIGDAWG obviates the error-prone reformatting needed to traffic data between multiple programs, and streamlines and standardizes the data-analysis process for case-control studies of highly polymorphic data. BIGDAWG has been implemented as the bigdawg R package and as a free web application at bigdawg.immunogenomics.org. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Breast cancer screening effect across breast density strata: A case-control study.

PubMed

van der Waal, Daniëlle; Ripping, Theodora M; Verbeek, André L M; Broeders, Mireille J M

2017-01-01

Breast cancer screening is known to reduce breast cancer mortality. A high breast density may affect this reduction. We assessed the effect of screening on breast cancer mortality in women with dense and fatty breasts separately. Analyses were performed within the Nijmegen (Dutch) screening programme (1975-2008), which invites women (aged 50-74 years) biennially. Performance measures were determined. Furthermore, a case-control study was performed for women having dense and women having fatty breasts. Breast density was assessed visually with a dichotomized Wolfe scale. Breast density data were available for cases. The prevalence of dense breasts among controls was estimated with age-specific rates from the general population. Sensitivity analyses were performed on these estimates. Screening performance was better in the fatty than in the dense group (sensitivity 75.7% vs 57.8%). The mortality reduction appeared to be smaller for women with dense breasts, with an odds ratio (OR) of 0.87 (95% CI 0.52-1.45) in the dense and 0.59 (95% CI 0.44-0.79) in the fatty group. We can conclude that high density results in lower screening performance and appears to be associated with a smaller mortality reduction. Breast density is thus a likely candidate for risk-stratified screening. More research is needed on the association between density and screening harms. © 2016 UICC.

Inverse association of plasma vanadium levels with newly diagnosed type 2 diabetes in a Chinese population.

PubMed

Wang, Xia; Sun, Taoping; Liu, Jun; Shan, Zhilei; Jin, Yilin; Chen, Sijing; Bao, Wei; Hu, Frank B; Liu, Liegang

2014-08-15

Vanadium compounds have been proposed to have beneficial effects on the pathogenesis and complications of type 2 diabetes. Our objective was to evaluate the association between plasma vanadium levels and type 2 diabetes. We performed a case-control study involving 1,598 Chinese subjects with or without newly diagnosed type 2 diabetes (December 2004-December 2007). Cases and controls were frequency-matched by age and sex. Plasma vanadium concentrations were measured and compared between groups. Analyses showed that plasma vanadium concentrations were significantly lower in cases with newly diagnosed type 2 diabetes than in controls (P = 0.001). Mean plasma vanadium levels in participants with and without diabetes were 1.0 μg/L and 1.2 μg/L, respectively. Participants in the highest quartile of plasma vanadium concentration had a notably lower risk of newly diagnosed type 2 diabetes (odds ratio = 0.26, 95% confidence interval: 0.19, 0.35; P < 0.001), compared with persons in the lowest quartile. The trend remained significant after adjustment for known risk factors and in further stratification analyses. Our results suggested that plasma vanadium concentrations were inversely associated with newly diagnosed type 2 diabetes in this Chinese population. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effect of an EBM course in combination with case method learning sessions: an RCT on professional performance, job satisfaction, and self-efficacy of occupational physicians.

PubMed

Hugenholtz, Nathalie I R; Schaafsma, Frederieke G; Nieuwenhuijsen, Karen; van Dijk, Frank J H

2008-10-01

An intervention existing of an evidence-based medicine (EBM) course in combination with case method learning sessions (CMLSs) was designed to enhance the professional performance, self-efficacy and job satisfaction of occupational physicians. A cluster randomized controlled trial was set up and data were collected through questionnaires at baseline (T0), directly after the intervention (T1) and 7 months after baseline (T2). The data of the intervention group [T0 (n = 49), T1 (n = 31), T2 (n = 29)] and control group [T0 (n = 49), T1 (n = 28), T2 (n = 28)] were analysed in mixed model analyses. Mean scores of the perceived value of the CMLS were calculated in the intervention group. The overall effect of the intervention over time comparing the intervention with the control group was statistically significant for professional performance (p < 0.001). Job satisfaction and self-efficacy changes were small and not statistically significant between the groups. The perceived value of the CMLS to gain new insights and to improve the quality of their performance increased with the number of sessions followed. An EBM course in combination with case method learning sessions is perceived as valuable and offers evidence to enhance the professional performance of occupational physicians. However, it does not seem to influence their self-efficacy and job satisfaction.

Thromboembolism Following Shoulder Arthroscopy

PubMed Central

Schick, Cameron W.; Westermann, Robert W.; Gao, Yubo; Abboud, Joseph A.; Wolf, Brian R.

2014-01-01

Background: Thromboembolism following shoulder arthroscopy is considered an uncommon complication, with fewer than 50 cases reported in the literature. Arthroscopy of the shoulder is one of the most commonly performed orthopaedic procedures, with low associated risks. Purpose: To identify potential risk factors for the development of venous thromboembolism (VTE) following shoulder arthroscopy and to determine the overall incidence of this complication. Study Design: Case-control study; Level of evidence, 3. Methods: A retrospective case-control review was performed of patients who developed symptomatic deep venous thrombosis (DVT) or pulmonary embolism (PE) following shoulder arthroscopy. Multiple surgeons from across North America were queried. For every case of DVT or PE identified, 2 control cases of shoulder arthroscopy were analyzed. The incidence of DVT/PE following shoulder arthroscopy was determined. A univariate analysis and a multivariate logistic regression model were conducted to identify any potential risk factors for the development of VTE following shoulder arthroscopy. Results: A total of 17 surgeons participated in this study and had performed a total of 15,033 cases of shoulder arthroscopy from September 2002 through August 2011. Eleven of the 17 participating surgeons had had a patient with a VTE complication during this time frame. The incidence of VTE in the 15,033 cases was 0.15%; 22 patients of the 15,033 patients had a DVT (n = 15) and/or PE (n = 8). Forty-four control cases were also analyzed. Univariate and multivariate analyses were performed. No significant risk factors were identified other than patient positioning. All cases and controls were positioned in the beach-chair position for surgery. Conclusion: The results of this study show that although rare, VTE occurs following shoulder arthroscopy at a rate of 0.15%. The variables analyzed in the cases of VTE compared with the control cases did not show any significant risk factors. All cases were positioned in the beach-chair position. Further analysis of future cases is warranted. PMID:26535285

Economic Evaluation of Community-Based Case Management of Patients Suffering From Chronic Obstructive Pulmonary Disease.

PubMed

Sørensen, Sabrina Storgaard; Pedersen, Kjeld Møller; Weinreich, Ulla Møller; Ehlers, Lars

2017-06-01

To analyse the cost effectiveness of community-based case management for patients suffering from chronic obstructive pulmonary disease (COPD). The study took place in the third largest municipality in Denmark and was conducted as a randomised controlled trial with 12 months of follow-up. A total of 150 patients with COPD were randomised into two groups receiving usual care and case management in addition to usual care. Case management included among other things self care proficiency, medicine compliance, and care coordination. Outcome measure for the analysis was the incremental cost-effectiveness ratio (ICER) as cost per quality-adjusted life year (QALY) from the perspective of the healthcare sector. Costs were valued in British Pounds (£) at price level 2016. Scenario analyses and probabilistic sensitivity analyses were conducted in order to assess uncertainty of the ICER estimate. The intervention resulted in a QALY improvement of 0.0146 (95% CI -0.0216; 0.0585), and a cost increase of £494 (95% CI -1778; 2766) per patient. No statistically significant difference was observed either in costs or effects. The ICER was £33,865 per QALY gained. Scenario analyses confirmed the robustness of the result and revealed slightly lower ICERs of £28,100-£31,340 per QALY. Analysis revealed that case management led to a positive incremental QALY, but were more costly than usual care. The highly uncertain ICER somewhat exceeds for instance the threshold value used by the National Institute of Health and Care Excellence (NICE). No formally established Danish threshold value exists. ClinicalTrials.gov Identifier: NCT01512836.

Exposure to Multiple Pesticides and Risk of Non-Hodgkin Lymphoma in Men from Six Canadian Provinces

PubMed Central

Hohenadel, Karin; Harris, Shelley A.; McLaughlin, John R.; Spinelli, John J.; Pahwa, Punam; Dosman, James A.; Demers, Paul A.; Blair, Aaron

2011-01-01

Non-Hodgkin lymphoma (NHL) has been linked to several agricultural exposures, including some commonly used pesticides. Although there is a significant body of literature examining the effects of exposure to individual pesticides on NHL, the impact of exposure to multiple pesticides or specific pesticide combinations has not been explored in depth. Data from a six-province Canadian case-control study conducted between 1991 and 1994 were analyzed to investigate the relationship between NHL, the total number of pesticides used and some common pesticide combinations. Cases (n = 513) were identified through hospital records and provincial cancer registries and controls (n = 1,506), frequency matched to cases by age and province of residence, were obtained through provincial health records, telephone listings, or voter lists. In multiple logistic regression analyses, risk of NHL increased with the number of pesticides used. Similar results were obtained in analyses restricted to herbicides, insecticides and several pesticide classes. Odds ratios increased further when only ‘potentially carcinogenic’ pesticides were considered (OR[one pesticide] = 1.30, 95% CI = 0.90–1.88; OR[two to four] = 1.54, CI = 1.11–2.12; OR[five or more] = 1.94, CI = 1.17–3.23). Elevated risks were also found among those reporting use of malathion in combination with several other pesticides. These analyses support and extend previous findings that the risk of NHL increases with the number of pesticides used and some pesticide combinations. PMID:21776232

Nested Event-Level Case-Control Study of Drug Use and Sexual Outcomes in Multipartner Encounters Reported by Men Who Have Sex with Men.

PubMed

Melendez-Torres, G J; Hickson, Ford; Reid, David; Weatherburn, Peter; Bonell, Chris

2016-03-01

Previous event-level analyses have often, but not always, found significant associations between drug use and sexual risk behaviour in men who have sex with men (MSM), but these analyses have rarely considered either multipartner encounters specifically, or other sexual outcomes such as pleasure and control. Using data from an internet-based longitudinal survey of MSM, we tested the association between drug use by respondent and by partners and unprotected anal intercourse (UAI), pleasure and control over sexual activity. Overall respondent substance use was significantly associated with increased odds of UAI, though not with pleasure or control. Respondent use of crystal methamphetamine was significantly associated with both increased odds of UAI and decreased odds of control over sexual activity. This analysis agrees with previous studies of dyadic encounters, and specifically suggests that the association between crystal methamphetamine and sexual risk behaviour may be mediated by loss of control.

Costs associated with implementation of a strict policy for controlling spread of highly resistant microorganisms in France.

PubMed

Birgand, Gabriel; Leroy, Christophe; Nerome, Simone; Luong Nguyen, Liem Binh; Lolom, Isabelle; Armand-Lefevre, Laurence; Ciotti, Céline; Lecorre, Bertrand; Marcade, Géraldine; Fihman, Vincent; Nicolas-Chanoine, Marie-Hélène; Pelat, Camille; Perozziello, Anne; Fantin, Bruno; Yazdanpanah, Yazdan; Ricard, Jean-Damien; Lucet, Jean-Christophe

2016-01-29

To assess costs associated with implementation of a strict 'search and isolate' strategy for controlling highly drug-resistant organisms (HDRO). Review of data from 2-year prospective surveillance (01/2012 to 12/2013) of HDRO. Three university hospitals located in northern Paris. Episodes were defined as single cases or outbreaks of glycopeptide-resistant enterococci (GRE) or carbapenemase-producing Enterobacteriacae (CPE) colonisation. Costs were related to staff reinforcement, costs of screening cultures, contact precautions and interruption of new admissions. Univariate analysis, along with simple and multiple linear regression analyses, was conducted to determine variables associated with cost of HDRO management. Overall, 41 consecutive episodes were included, 28 single cases and 13 outbreaks. The cost (mean ± SD) associated with management of a single case identified within and/or 48 h after admission was €4443 ± 11,552 and €11,445 ± 15,743, respectively (p<0.01). In an outbreak, the total cost varied from €14,864 ± 17,734 for an episode with one secondary case (€7432 ± 8867 per case) to €136,525 ± 151,231 (€12,845 ± 5129 per case) when more than one secondary case occurred. In episodes of single cases, contact precautions and microbiological analyses represented 51% and 30% of overall cost, respectively. In outbreaks, cost related to interruption of new admissions represented 77-94% of total costs, and had the greatest financial impact (R(2)=0.98, p<0.01). In HDRO episodes occurring at three university hospitals, interruption of new admissions constituted the most costly measure in an outbreak situation. 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/

Asthma in changing environments - chances and challenges of international research collaborations between South America and Europe - study protocol and description of the data acquisition of a case-control-study

PubMed Central

2010-01-01

Background Asthma in children is an emerging public health problem in South America. So far, research in this part of the world is limited. This paper presents the methodology and description of the data acquisition of an asthma case-control study conducted in the Central South of Chile. Methods/Design A hospital-based case-control study about asthma (188 cases, 294 controls) in children (6-15 years) was carried out in Valdivia, Chile between November 2008 and December 2009. Data on asthma risk factors were collected by computer-assisted personal interview using validated questions from e.g. ISAAC phase II. Data on household dust exposure (endotoxin, allergen analyses), skin prick tests to most common allergens, stool examinations for parasitic infection, and blood samples (total IgE, genetics) were collected. Additionally, 492 randomly chosen blood donors were recruited in order to assess allele frequencies in the population of Valdivia. Discussion Overall 1,173 participants were contacted. Response was 82% among cases and 65% among controls. Atopic sensitization was high (78% among cases, 47% among controls). Cases had a statistically significantly (p < .0001) increased self-reported 12-month prevalence of symptoms of rhinitis (82% vs. 51%) and wheeze (68% vs. 16%). The study is well placed to address current hypotheses about asthma and its correlates in the South American context. Results of this study might help develop novel, innovative and individualized prevention strategies in countries in transition with respect to the South American context. PMID:20718949

Gut microbiota in Parkinson disease in a northern German cohort.

PubMed

Hopfner, Franziska; Künstner, Axel; Müller, Stefanie H; Künzel, Sven; Zeuner, Kirsten E; Margraf, Nils G; Deuschl, Günther; Baines, John F; Kuhlenbäumer, Gregor

2017-07-15

Pathologic and epidemiologic studies suggest that Parkinson disease (PD) may in some cases start in the enteric nervous system and spread via the vagal nerve to the brainstem. Mounting evidence suggests that the gut microbiome plays an important role in the communication between gut and brain and that alteration of the gut microbiome is involved in the pathogenesis of numerous diseases, including Parkinson disease. The aim of this study was to determine whether Parkinson disease is associated with qualitative or quantitative changes in the gut microbiome. We analyzed the gut microbiome in 29 PD cases and 29 age-matched controls by next-generation-sequencing of the 16S rRNA gene and compared diversity indices and bacterial abundances between cases and controls. Alpha diversity measures and the abundance of major phyla did not differ between cases and controls. Beta diversity analyses and analysis on the bacterial family level revealed significant differences between cases and controls for four bacterial families. In keeping with recently published studies, Lactobacillaceae were more abundant in cases. Barnesiellaceae and Enterococcacea were also more abundant in cases in this study but not in other studies. Larger studies, accounting for drug effects and further functional investigations of the gut microbiome are necessary to delineate the role of the gut microbiome in the pathogenesis of PD. Copyright © 2017 Elsevier B.V. All rights reserved.

Matrix metalloproteinase-2 gene variants and abdominal aortic aneurysm.

PubMed

Smallwood, L; Warrington, N; Allcock, R; van Bockxmeer, F; Palmer, L J; Iacopetta, B; Golledge, J; Norman, P E

2009-08-01

To investigate associations between two polymorphisms of the matrix metalloproteinase-2 gene (MMP2) and the incidence and progression of abdominal aortic aneurysm (AAA). Cases and controls were recruited from a trial of screening for AAAs. The association between two variants of MMP2 (-1360C>T, and +649C>T) in men with AAA (n=678) and in controls (n=659) was examined using multivariate analyses. The association with AAA expansion (n=638) was also assessed. In multivariate analyses with adjustments for multiple testing, no association between either SNP and AAA presence or expansion was detected. MMP2 -1360C>T and +649C>T variants are not risk factors for AAA.

Impact of Muscarinic M3 Receptor Antagonism on the Risk of Type 2 Diabetes in Antidepressant-Treated Patients: A Case-Controlled Study.

PubMed

Tran, Yen-Hao; Schuiling-Veninga, Catharina C M; Bergman, Jorieke E H; Groen, Henk; Wilffert, Bob

2017-06-01

M 3 muscarinic receptor antagonism has been associated with glucose intolerance and disturbance of insulin secretion. Our objective was to examine the risk of type 2 diabetes mellitus (T2DM) in patients using antidepressants with and without M 3 muscarinic receptor antagonism (AD_antaM 3 and AD_nonantaM 3 , respectively). We designed a case-control study using a pharmacy prescription database. We selected a cohort of patients who initiated antidepressant use between the ages of 20 and 40 years and who did not receive any anti-diabetic prescriptions at baseline. Cases were defined as those who developed T2DM [i.e., receiving oral anti-diabetic medication, Anatomical Therapeutic Chemical (ATC) code A10B] during the follow-up period (1994-2014), and ten random controls were picked for each case from the cohort of patients who did not develop T2DM. A total of 530 cases with incident T2DM and 5300 controls were included. Compared with no use of antidepressants during the previous 2 years, recent (within the last 6 months) exposure to AD_antaM 3 was associated with a moderately increased risk of T2DM: adjusted odds ratio 1.55 (95% confidence interval 1.18-2.02). In the stratified analyses, this association was dose dependent (>365 defined daily doses) and significant for patients who were in the younger age group (<45 years at the end of follow-up), were female and had no co-morbidity. On the other hand, recent exposure to AD_nonantaM 3 was not associated with a risk for T2DM in any of our analyses. Our results suggest that exposure to AD_antaM 3 was associated with the development of T2DM among antidepressant users.

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

PubMed

Cordell, Heather J; Han, Younghun; Mells, George F; Li, Yafang; Hirschfield, Gideon M; Greene, Casey S; Xie, Gang; Juran, Brian D; Zhu, Dakai; Qian, David C; Floyd, James A B; Morley, Katherine I; Prati, Daniele; Lleo, Ana; Cusi, Daniele; Gershwin, M Eric; Anderson, Carl A; Lazaridis, Konstantinos N; Invernizzi, Pietro; Seldin, Michael F; Sandford, Richard N; Amos, Christopher I; Siminovitch, Katherine A

2015-09-22

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

Risk factors for oral and pharyngeal cancer in women: a study from Italy and Switzerland

PubMed Central

Bosetti, C; Negri, E; Franceschi, S; Conti, E; Levi, F; Tomei, F; Vecchia, C La

1999-01-01

We analysed two case–control studies of women from Italy and Switzerland, including 195 cases of oral and pharyngeal cancers and 1113 controls. The multivariate odds ratio was 4.6 for heavy smokers and 2.7 for high alcohol intake. Vegetables, fruit, β-carotene and wholegrain foods were inversely, butter and retinol directly, related to risk. © 2000 Cancer Research Campaign PMID:10638990

Control of a Vanadium Redox Battery and supercapacitor using a Three-Level Neutral Point Clamped converter

NASA Astrophysics Data System (ADS)

Etxeberria, A.; Vechiu, I.; Baudoin, S.; Camblong, H.; Kreckelbergh, S.

2014-02-01

The increasing use of distributed generators, which are mainly based on renewable sources, can create several issues in the operation of the electric grid. The microgrid is being analysed as a solution to the integration in the grid of the renewable sources at a high penetration level in a controlled way. The storage systems play a vital role in order to keep the energy and power balance of the microgrid. Due to the technical limitations of the currently available storage systems, it is necessary to use more than one storage technology to satisfy the requirements of the microgrid application. This work validates in simulations and experimentally the use of a Three-Level Neutral Point Clamped converter to control the power flow of a hybrid storage system formed by a SuperCapacitor and a Vanadium Redox Battery. The operation of the system is validated in two case studies in the experimental platform installed in ESTIA. The experimental results prove the validity of the proposed system as well as the designed control algorithm. The good agreement among experimental and simulation results also validates the simulation model, that can therefore be used to analyse the operation of the system in different case studies.

The Economic Burden of Urinary Tract Infection and Pressure Ulceration in Acute Traumatic Spinal Cord Injury Admissions: Evidence for Comparative Economics and Decision Analytics from a Matched Case-Control Study.

PubMed

White, Barry A B; Dea, Nicolas; Street, John T; Cheng, Christiana L; Rivers, Carly S; Attabib, Najmedden; Kwon, Brian K; Fisher, Charles G; Dvorak, Marcel F

2017-10-15

Secondary complications of spinal cord injury (SCI) are a burden to affected individuals and the rest of society. There is limited evidence of the economic burden or cost of complications in SCI populations in Canada, however, which is necessary for comparative economic analyses and decision analytic modeling of possible solutions to these common health problems. Comparative economic analyses can inform resource allocation decisions, but the outputs are only as good as the inputs. In this article, new evidence of the excess or incremental costs of urinary tract infection (UTI) and pressure ulceration (PU) in acute traumatic SCI from an exploratory case series analysis of admissions to a Level I specialized Canadian spine facility (2008-2013) is presented. Participants in a national SCI registry were case-control matched (1:1) on the predicted probability of experiencing UTI or PU during initial acute SCI admission. The excess costs of UTI and PU are estimated as the mean of the differences in total direct acute SCI admission costs (length of stay, accommodation, nursing, pharmacy) from the perspective of the admitting facility between participants matched or paired on demographic and SCI characteristics. Even relatively minor UTI and PU, respectively, added an average of $7,790 (standard deviation [SD] $6,267) and $18,758 (SD $27,574) to the direct cost of acute SCI admission in 2013 Canadian dollars (CAD). This case series analysis established evidence of the excess costs of UTI and PU in acute SCI admissions, which will support decision-informing analyses in SCI.

Stroke Genetics Network (SiGN) Study: Design and rationale for a genome-wide association study of ischemic stroke subtypes

PubMed Central

Meschia, James F.; Arnett, Donna K.; Ay, Hakan; Brown, Robert D.; Benavente, Oscar; Cole, John W.; de Bakker, Paul I.W.; Dichgans, Martin; Doheny, Kimberly F.; Fornage, Myriam; Grewal, Raji; Gwinn, Katrina; Jern, Christina; Conde, Jordi Jimenez; Johnson, Julie A.; Jood, Katarina; Laurie, Cathy C.; Lee, Jin-Moo; Lindgren, Arne; Markus, Hugh S.; McArdle, Patrick F.; McClure, Leslie A.; Mitchell, Braxton D.; Schmidt, Reinhold; Rexrode, Kathryn M.; Rich, Stephen S.; Rosand, Jonathan; Rothwell, Peter M.; Rundek, Tatjana; Sacco, Ralph L.; Sharma, Pankaj; Shuldiner, Alan R.; Slowik, Agnieszka; Wassertheil-Smoller, Sylvia; Sudlow, Cathie; Thijs, Vincent; Woo, Daniel; Worrall, Bradford B.; Wu, Ona; Kittner, Steven J.

2014-01-01

Background and Purpose Meta-analyses of extant genome-wide data illustrate the need to focus on subtypes of ischemic stroke for gene discovery. The NINDS Stroke Genetics Network (SiGN) contributes substantially to meta-analyses that focus on specific subtypes of stroke. Methods The NINDS Stroke Genetics Network (SiGN) includes ischemic stroke cases from 24 Genetic Research Centers (GRCs), 13 from the US and 11 from Europe. Investigators harmonize ischemic stroke phenotyping using the web-based Causative Classification of Stroke (CCS) system, with data entered by trained and certified adjudicators at participating GRCs. Through the Center for Inherited Diseases Research (CIDR), SiGN plans to genotype 10,296 carefully phenotyped stroke cases using genome-wide SNP arrays, and add to these another 4,253 previously genotyped cases for a total of 14,549 cases. To maximize power for subtype analyses, the study allocates genotyping resources almost exclusively to cases. Publicly available studies provide most of the control genotypes. CIDR-generated genotypes and corresponding phenotypic data will be shared with the scientific community through dbGaP, and brain MRI studies will be centrally archived. Conclusions The SiGN consortium, with its emphasis on careful and standardized phenotyping of ischemic stroke and stroke subtypes, provides an unprecedented opportunity to uncover genetic determinants of ischemic stroke. PMID:24021684

Premature death of adult adoptees: analyses of a case-cohort sample.

PubMed

Petersen, Liselotte; Andersen, Per Kragh; Sørensen, Thorkild I A

2005-05-01

Genetic and environmental influence on risk of premature death in adulthood was investigated by estimating the associations in total and cause-specific mortality of adult Danish adoptees and their biological and adoptive parents. Among all 14,425 non-familial adoptions formally granted in Denmark during the period 1924 through 1947, we selected the study population according to a case-cohort sampling design. As the case-control design, the case-cohort design has the advantage of economic data collection and little loss in statistical efficiency, but the case-cohort sample has the additional advantages that rate ratio estimates may be obtained, and re-use of the cohort sample in future studies of other outcomes is possible. Analyses were performed using Kalbfleisch and Lawless's estimator for hazard ratio, and robust estimation for variances. In the main analyses the sample was restricted to birth years of the adoptees 1924 and after, and age of transfer to the adoptive parents before 7 years, and age at death was restricted to 16 to 70 years. The results showed a higher mortality among adoptees, whose biological parents died in the age range of 16 to 70 years; this was significant for deaths from natural causes, vascular causes and all causes. No influence was seen from early death of adoptive parents, regardless of cause of death. (c) 2005 Wiley-Liss, Inc.

Development and validation of a melanoma risk score based on pooled data from 16 case-control studies

PubMed Central

Davies, John R; Chang, Yu-mei; Bishop, D Timothy; Armstrong, Bruce K; Bataille, Veronique; Bergman, Wilma; Berwick, Marianne; Bracci, Paige M; Elwood, J Mark; Ernstoff, Marc S; Green, Adele; Gruis, Nelleke A; Holly, Elizabeth A; Ingvar, Christian; Kanetsky, Peter A; Karagas, Margaret R; Lee, Tim K; Le Marchand, Loïc; Mackie, Rona M; Olsson, Håkan; Østerlind, Anne; Rebbeck, Timothy R; Reich, Kristian; Sasieni, Peter; Siskind, Victor; Swerdlow, Anthony J; Titus, Linda; Zens, Michael S; Ziegler, Andreas; Gallagher, Richard P.; Barrett, Jennifer H; Newton-Bishop, Julia

2015-01-01

Background We report the development of a cutaneous melanoma risk algorithm based upon 7 factors; hair colour, skin type, family history, freckling, nevus count, number of large nevi and history of sunburn, intended to form the basis of a self-assessment webtool for the general public. Methods Predicted odds of melanoma were estimated by analysing a pooled dataset from 16 case-control studies using logistic random coefficients models. Risk categories were defined based on the distribution of the predicted odds in the controls from these studies. Imputation was used to estimate missing data in the pooled datasets. The 30th, 60th and 90th centiles were used to distribute individuals into four risk groups for their age, sex and geographic location. Cross-validation was used to test the robustness of the thresholds for each group by leaving out each study one by one. Performance of the model was assessed in an independent UK case-control study dataset. Results Cross-validation confirmed the robustness of the threshold estimates. Cases and controls were well discriminated in the independent dataset (area under the curve 0.75, 95% CI 0.73-0.78). 29% of cases were in the highest risk group compared with 7% of controls, and 43% of controls were in the lowest risk group compared with 13% of cases. Conclusion We have identified a composite score representing an estimate of relative risk and successfully validated this score in an independent dataset. Impact This score may be a useful tool to inform members of the public about their melanoma risk. PMID:25713022

CASE STUDIES IN THE INTEGRATED USE OF SCALE ANALYSES TO SOLVE LEAD PROBLEMS

EPA Science Inventory

All methods of controlling lead corrosion involve immobilizing lead into relatively insoluble compounds that deposit on the interior wall of water pipes. Many different solid phases can form under the disparate conditions that exist in distribution systems, which range in how the...

Natural History of Breast Density and Breast Cancer Risk

DTIC Science & Technology

2001-07-01

mammography database. We have estimated breast density on the oldest mammogram from both cases and controls, using our semi-automated software and...using the oldest mammogram) with breast cancer risk. Next winter, we will continue these analyses investigating the change in density over time and

Predictors of social anxiety in an opioid dependent sample and a control sample.

PubMed

Shand, Fiona L; Degenhardt, Louisa; Nelson, Elliot C; Mattick, Richard P

2010-01-01

Compared to other mental health problems, social anxiety is under-acknowledged amongst opioid dependent populations. This study aimed to assess levels of social anxiety and identify its predictors in an opioid dependent sample and a matched control group. Opioid dependent participants (n=1385) and controls (n=417) completed the Social Interaction Anxiety Scale (SIAS), the Social Phobia Scale (SPS) and a diagnostic interview. Regression analyses were used to test a range of predictors of social anxiety. Opioid dependent cases had higher mean scores on both scales compared to controls. Predictors of social anxiety centred on emotional rejection in childhood, either by parents or peers. For opioid dependent cases, but not controls, lifetime non-opioid substance dependence (cannabis, sedatives, and tobacco) was associated with higher levels of social anxiety. However, much of the variance in social anxiety remains unexplained for this population.

Predictors of social anxiety in an opioid dependent sample and a control sample

PubMed Central

Shand, Fiona L.; Degenhardt, Louisa; Nelson, Elliot C.; Mattick, Richard P.

2010-01-01

Compared to other mental health problems, social anxiety is under-acknowledged amongst opioid dependent populations. This study aimed to assess levels of social anxiety and identify its predictors in an opioid dependent sample and a matched control group. Opioid dependent participants (n = 1385) and controls (n = 417) completed the Social Interaction Anxiety Scale (SIAS), the Social Phobia Scale (SPS) and a diagnostic interview. Regression analyses were used to test a range of predictors of social anxiety. Opioid dependent cases had higher mean scores on both scales compared to controls. Predictors of social anxiety centred on emotional rejection in childhood, either by parents or peers. For opioid dependent cases, but not controls, lifetime non-opioid substance dependence (cannabis, sedatives, and tobacco) was associated with higher levels of social anxiety. However, much of the variance in social anxiety remains unexplained for this population. PMID:19775865

Deep venous thrombosis associated with corporate air travel.

PubMed

Dimberg, L A; Mundt, K A; Sulsky, S I; Liese, B H

2001-01-01

Deep venous thrombosis (DVT) is commonly seen among bedridden and postoperative patients. Its association with travel may also make DVT an occupational health risk to otherwise healthy business travelers. We estimated the incidence of and risk factors for DVT among 8,189 World Bank employees and a subset of 4,951 international business travelers. Occurrence of DVT between 1995 and 1998 was determined using 1) medical insurance claims; 2) Workers' Compensation claims; and 3) intra-office E-mail solicitation followed by interview. For each insurance claim case, 10 controls were randomly selected from among World Bank employees insured during the same month and year as the case's claim was filed, and case-control analyses were performed to identify potential predictors or risk factors for DVT. Thirty individuals filed claims for DVT of the legs (annual incidence rate: 0.9 per 1,000 employees); three of these claims were filed within 30 days after a travel mission. Two employees reported DVT as a Workers' Compensation injury, and five staff with verified DVT participated in interviews. After controlling for age and gender, no association with any travel-related covariate was seen. Results of analyses considering all thrombophlebitis and thromboembolism followed the same pattern. The average annual incidence of DVT occurring within 30 days of mission among traveling staff ranged from 0.10 per 1,000 to 0.25 per 1,000 travelers, depending on the case-finding method. No association between DVT and travel was observed after adjustment for gender and age. These results, however, are preliminary, and due to the rarity of DVT, based on small numbers.

Autoantibodies to MUC1 glycopeptides cannot be used as a screening assay for early detection of breast, ovarian, lung or pancreatic cancer

PubMed Central

Burford, B; Gentry-Maharaj, A; Graham, R; Allen, D; Pedersen, J W; Nudelman, A S; Blixt, O; Fourkala, E O; Bueti, D; Dawnay, A; Ford, J; Desai, R; David, L; Trinder, P; Acres, B; Schwientek, T; Gammerman, A; Reis, C A; Silva, L; Osório, H; Hallett, R; Wandall, H H; Mandel, U; Hollingsworth, M A; Jacobs, I; Fentiman, I; Clausen, H; Taylor-Papadimitriou, J; Menon, U; Burchell, J M

2013-01-01

Background: Autoantibodies have been detected in sera before diagnosis of cancer leading to interest in their potential as screening/early detection biomarkers. As we have found autoantibodies to MUC1 glycopeptides to be elevated in early-stage breast cancer patients, in this study we analysed these autoantibodies in large population cohorts of sera taken before cancer diagnosis. Methods: Serum samples from women who subsequently developed breast cancer, and aged-matched controls, were identified from UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) and Guernsey serum banks to formed discovery and validation sets. These were screened on a microarray platform of 60mer MUC1 glycopeptides and recombinant MUC1 containing 16 tandem repeats. Additional case–control sets comprised of women who subsequently developed ovarian, pancreatic and lung cancer were also screened on the arrays. Results: In the discovery (273 cases, 273 controls) and the two validation sets (UKCTOCS 426 cases, 426 controls; Guernsey 303 cases and 606 controls), no differences were found in autoantibody reactivity to MUC1 tandem repeat peptide or glycoforms between cases and controls. Furthermore, no differences were observed between ovarian, pancreatic and lung cancer cases and controls. Conclusion: This robust, validated study shows autoantibodies to MUC1 peptide or glycopeptides cannot be used for breast, ovarian, lung or pancreatic cancer screening. This has significant implications for research on the use of MUC1 in cancer detection. PMID:23652307

Home pesticide exposures and risk of childhood leukemia: Findings from the Childhood Leukemia International Consortium

PubMed Central

Bailey, Helen D; Infante-Rivard, Claire; Metayer, Catherine; Clavel, Jacqueline; Lightfoot, Tracy; Kaatsch, Peter; Roman, Eve; Magnani, Corrado; Spector, Logan G; Petridou, Eleni; Milne, Elizabeth; Dockerty, John D; Miligi, Lucia; Armstrong, Bruce K; Rudant, Jérémie; Fritschi, Lin; Simpson, Jill; Zhang, Luoping; Rondelli, Roberto; Baka, Margarita; Orsi, Laurent; Moschovi, Maria; Kang, Alice Y; Schüz, Joachim

2015-01-01

Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, we pooled individual level data from 12 case-control studies in the Childhood Leukemia International Consortium (CLIC). Exposure data were harmonized into compatible formats. Pooled analyses were undertaken using multivariable unconditional logistic regression. The odds ratio (ORs) for acute lymphoblastic leukaemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39 (95% confidence interval (CI) 1.25, 1.55) (using (2,785 cases, 3635 controls), 1.43 (95% CI 1.32, 1.54) (5,055 cases, 7,370 controls) and 1.36 (95% CI 1.23, 1.51) (4,162 cases 5,179 controls), respectively. Corresponding ORs for risk of acute myeloid leukaemia (AML) were 1.49 (95% CI 1.02, 2.16) (173 cases, 1,789 controls), 1.55 (95% CI 1.21, 1.99) (344 cases, 4,666 controls) and 1.08 (95% CI 0.76, 1.53) (198 cases, 2,655 controls) respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukaemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants’ exposure to multiple pesticides, or recall bias. Although some recall bias is likely, until a better study design can be found to investigate associations between home pesticide use and childhood leukaemia in an equally large sample, it would appear prudent to limit the use of home pesticides before and during pregnancy, and during childhood. PMID:26061779

Are dietary reports in a case-control study on thyroid cancer biased by risk perception of Chernobyl fallout?

PubMed

Xhaard, C; Dumas, A; Souchard, V; Ren, Y; Borson-Chazot, F; Sassolas, G; Schvartz, C; Colonna, M; Lacour, B; Wonoroff, A S; Velten, M; Clero, E; Maillard, S; Marrer, E; Bailly, L; Mariné Barjoan, E; Schlumberger, M; Orgiazzi, J; Adjadj, E; Rubino, C; Bouville, A; Drozdovitch, V; de Vathaire, F

2017-08-01

In retrospective case-control studies performed following nuclear tests or nuclear accidents, individual thyroid radiation dose reconstructions are based on fallout and meteorological data from the residential area, demographic characteristics, and lifestyle as well as dietary information. Collecting the latter is a controversial step, as dietary declarations may be affected by the subjects' beliefs about their risk behavior. This report analyses the potential for such bias in a case-control study performed in eastern France. The study included 765 cases of differentiated thyroid carcinoma matched with 831 controls. Risk perceptions and beliefs of cases and controls were compared using Chi 2 tests and differences in dietary reports were analyzed using a two-way ANOVA. In general, atmospheric pollution and living near a nuclear power plant were the two major risks that may influence thyroid cancer occurrence cited by cases and controls. When focusing in particular on the consequences of the Chernobyl accident, cases were more likely to think that the consequences were responsible for thyroid cancer occurrence than controls. Vegetable consumption during the two months after the Chernobyl accident was correlated with the status of subjects, but not to their beliefs. Conversely, consumption of fresh dairy products was not correlated with the status or beliefs of subjects. We found no evidence of systematic bias in dietary reports according to the status or beliefs held by subjects about the link between thyroid cancer occurrence and Chernobyl fallout. As such, these dietary reports may be used in further studies involving individual dosimetric reconstructions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study

PubMed Central

Ivers, Louise C; Hilaire, Isabelle J; Teng, Jessica E; Almazor, Charles P; Jerome, J Gregory; Ternier, Ralph; Boncy, Jacques; Buteau, Josiane; Murray, Megan B; Harris, Jason B; Franke, Molly F

2015-01-01

Background Between April and June 2012, a reactive cholera vaccination campaign was conducted in Haiti using an oral inactivated bivalent whole-cell vaccine (BivWC). Methods We conducted a case-control study to estimate field effectiveness of the vaccine. Cases had acute watery diarrhea, sought treatment at one of three participating cholera treatment units from October 24, 2012 through March 9, 2014, and had a stool sample positive for cholera by culture. For each case, four controls (individuals who did not seek treatment for acute watery diarrhea) were matched by location of residence, calendar time, and age. We also conducted a bias-indicator case-control study to assess the likelihood of bias in the vaccine effectiveness (VE) study. Findings During the study period, 114 eligible individuals presented with acute watery diarrhea and were enrolled. 47 were analyzed as cases in the VE case-control study and 42 as cases in the bias-indicator study. In multivariable analyses, VE was 63% [95% confidence interval (CI): 8%–85%] by self-reported vaccination and 58% [95% CI: 13%–80%] for verified vaccination. Neither self-reported nor verified vaccination was significantly associated with non-cholera diarrhea (VE: 18% [95% CI: −208%–−78%] by self-report and −21% [95%CI: −238%–57%] for verified vaccination). Interpretation BivWC oral cholera vaccine was effective in protecting against cholera in Haiti during the study period –from 4 through 24 months after vaccination. Vaccination is an important component of epidemic cholera control efforts. Funding National Institutes of Health, Delivering Oral Vaccines Effectively project, Department of Global Health and Social Medicine at Harvard Medical School. PMID:25701994

Risk factors for mumps at a university with a large mumps outbreak.

PubMed

Huang, Angela S; Cortese, Margaret M; Curns, Aaron T; Bitsko, Rebecca H; Jordan, Hannah T; Soud, Fatma; Villalon-Gomez, Jose; Denning, Patricia M; Ens, Kim A; Hanson, Gail R; Dayan, Gustavo H

2009-01-01

Routine measles-mumps-rubella (MMR) vaccine use has greatly decreased the incidence of mumps in the U.S. However, a resurgence of mumps occurred in 2006. We investigated the large outbreak at a university and assessed risk factors for disease. We described the outbreak and conducted a case-control study. We interviewed case students (identified from student health service and health department records) and control students (selected from a randomly ordered administrative list) and assessed their vaccination status. We compared case students with > or = 2 MMR doses and control students with > or = 2 MMR doses in univariate and multivariate analyses. The mean age of the 174 case students was 20.9 years; 65% were women. Ninety-seven case students and 147 control students were enrolled in the study. Two-dose MMR coverage was 99% among case and control students with complete records. Only 33% of case students reported exposure to someone with mumps. Case students were more likely than control students to be aged 18 to 19 years (vs. aged 22 years, adjusted odds ratio [AOR] = 5.55; 95% confidence interval [CI] 2.09, 14.74), to report exposure to mumps (AOR=2.31, 95% CI 1.13, 4.73), and to have worked/volunteered on campus (AOR=2.91, 95% CI 1.33, 6.33). Also, women in dormitories had increased odds of mumps compared with men in dormitories. High two-dose MMR coverage was not sufficient to prevent the outbreak. Further study is needed to better understand the effects of dormitory residency and gender on mumps transmission. Clinicians should be vigilant for mumps in young adults presenting with parotitis regardless of immunization history.

Intensive cognitive therapy for post-traumatic stress disorder in routine clinical practice: A matched comparison audit.

PubMed

Murray, Hannah; El-Leithy, Sharif; Billings, Jo

2017-11-01

Intensive cognitive therapy for post-traumatic stress disorder (PTSD) has been shown to be as effective as weekly treatment in controlled trials. In this study, outcome data comparing standard and intensive treatments delivered in routine clinical practice were analysed. A consecutive case series of intensive treatment cases were compared to matched control cases who had completed weekly treatment. Both groups showed significant improvements on PTSD and depression measures. The intensive group showed larger PTSD symptomatic improvement. There were differences between the groups in age and time since trauma, suggesting selection biases in who is offered, and/or who chooses intensive treatment. For some individuals, an intensive format may be more effective than weekly treatment. © 2017 The British Psychological Society.

[Differentiation of coding quality in orthopaedics by special, illustration-oriented case group analysis in the G-DRG System 2005].

PubMed

Schütz, U; Reichel, H; Dreinhöfer, K

2007-01-01

We introduce a grouping system for clinical practice which allows the separation of DRG coding in specific orthopaedic groups based on anatomic regions, operative procedures, therapeutic interventions and morbidity equivalent diagnosis groups. With this, a differentiated aim-oriented analysis of illustrated internal DRG data becomes possible. The group-specific difference of the coding quality between the DRG groups following primary coding by the orthopaedic surgeon and final coding by the medical controlling is analysed. In a consecutive series of 1600 patients parallel documentation and group-specific comparison of the relevant DRG parameters were carried out in every case after primary and final coding. Analysing the group-specific share in the additional CaseMix coding, the group "spine surgery" dominated, closely followed by the groups "arthroplasty" and "surgery due to infection, tumours, diabetes". Altogether, additional cost-weight-relevant coding was necessary most frequently in the latter group (84%), followed by group "spine surgery" (65%). In DRGs representing conservative orthopaedic treatment documented procedures had nearly no influence on the cost weight. The introduced system of case group analysis in internal DRG documentation can lead to the detection of specific problems in primary coding and cost-weight relevant changes of the case mix. As an instrument for internal process control in the orthopaedic field, it can serve as a communicative interface between an economically oriented classification of the hospital performance and a specific problem solution of the medical staff involved in the department management.

Efficacy of cognitive-behavioral therapy for childhood anxiety and depression.

PubMed

Crowe, Katherine; McKay, Dean

2017-06-01

A review of meta-analyses of cognitive-behavioral therapy (CBT) for childhood anxiety and depression was conducted. A total of 36 meta-analyses were identified that met inclusion criteria for this review. In most cases, medium-to-large effect sizes for treatment reduction were observed when CBT was compared to non-active control conditions. Small-to-medium effects were observed when CBT was compared to active control treatments. The available meta-analyses generally did not examine, or data were not sufficient to evaluate, potential moderators of outcome, differential effects for parental involvement, or changes in quality of life or functional outcomes associated with treatment. Accordingly, while CBT should be broadly considered an effective treatment approach for childhood anxiety and depression, additional research is warranted in order to establish guidelines for service delivery for complicating factors in client presentation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relationship between Long Chain n-3 Polyunsaturated Fatty Acids and Autism Spectrum Disorder: Systematic Review and Meta-Analysis of Case-Control and Randomised Controlled Trials

PubMed Central

Mazahery, Hajar; Stonehouse, Welma; Delshad, Maryam; Kruger, Marlena C.; Conlon, Cathryn A.; Beck, Kathryn L.; von Hurst, Pamela R.

2017-01-01

Omega-3 long chain polyunsaturated fatty acid supplementation (n-3 LCPUFA) for treatment of Autism Spectrum Disorder (ASD) is popular. The results of previous systematic reviews and meta-analyses of n-3 LCPUFA supplementation on ASD outcomes were inconclusive. Two meta-analyses were conducted; meta-analysis 1 compared blood levels of LCPUFA and their ratios arachidonic acid (ARA) to docosahexaenoic acid (DHA), ARA to eicosapentaenoic acid (EPA), or total n-6 to total n-3 LCPUFA in ASD to those of typically developing individuals (with no neurodevelopmental disorders), and meta-analysis 2 compared the effects of n-3 LCPUFA supplementation to placebo on symptoms of ASD. Case-control studies and randomised controlled trials (RCTs) were identified searching electronic databases up to May, 2016. Mean differences were pooled and analysed using inverse variance models. Heterogeneity was assessed using I2 statistic. Fifteen case-control studies (n = 1193) were reviewed. Compared with typically developed, ASD populations had lower DHA (−2.14 [95% CI −3.22 to −1.07]; p < 0.0001; I2 = 97%), EPA (−0.72 [95% CI −1.25 to −0.18]; p = 0.008; I2 = 88%), and ARA (−0.83 [95% CI, −1.48 to −0.17]; p = 0.01; I2 = 96%) and higher total n-6 LCPUFA to n-3 LCPUFA ratio (0.42 [95% CI 0.06 to 0.78]; p = 0.02; I2 = 74%). Four RCTs were included in meta-analysis 2 (n = 107). Compared with placebo, n-3 LCPUFA improved social interaction (−1.96 [95% CI −3.5 to −0.34]; p = 0.02; I2 = 0) and repetitive and restricted interests and behaviours (−1.08 [95% CI −2.17 to −0.01]; p = 0.05; I2 = 0). Populations with ASD have lower n-3 LCPUFA status and n-3 LCPUFA supplementation can potentially improve some ASD symptoms. Further research with large sample size and adequate study duration is warranted to confirm the efficacy of n-3 LCPUFA. PMID:28218722

G-protein beta 3 subunit polymorphisms and essential hypertension: a case-control association study in northern Han Chinese

PubMed Central

Li, Mei; Zhang, Bei; Li, Chuang; Liu, Jie-Lin; Wang, Li-Juan; Liu, Ya; Wang, Zuo-Guang; Wen, Shao-Jun

2015-01-01

Objective To explore the association between the three polymorphisms [ C825T, C1429T and G(-350)A] of the gene encoding the G protein beta 3 subunit (GNB3) and hypertension by performing a case-control study in the northern Han Chinese population. Methods We recruited 731 hypertensive patients and 673 control subjects (the calculated power value was > 0.8). Genotyping was performed to identify C825T, C1429T and G(-350)A polymorphisms using the TaqMan assay. Comparisons of allelic and genotypic frequencies between cases and controls were made by using the chi-square test. Logistic regression analyses were performed to investigate the relationships between the three polymorphisms of GNB3 gene under different genetic models (additive, dominant and recessive models). Results The genotype distribution and allele frequencies of C825T, C1429T and G(-350)A polymorphisms did not differ significantly between hypertensive patients and control subjects, either when the full sample was assessed, or when the sample was stratified by gender. No significant association was observed between C825T, C1429T and G(-350)A polymorphisms and the risk of essential hypertension in any genetic model. Linkage disequilibrium was only detected between C825T and C1429T polymorphisms. Haplotype analyses observed that none of the three estimated haplotypes significantly increased the risk of hypertension. Conclusions Our study suggested that the GNB3 gene polymorphisms [C825T, C1429T and G(-350)A] were not significantly associated with essential hypertension in northern Han Chinese population. PMID:25870615

Anti-doping analyses at the Sochi Olympic and Paralympic Games 2014.

PubMed

Sobolevsky, Tim; Krotov, Grigory; Dikunets, Marina; Nikitina, Maria; Mochalova, Elena; Rodchenkov, Grigory

2014-01-01

The laboratory anti-doping services during XXII Winter Olympic and XI Paralympic games in Sochi in 2014 were provided by a satellite laboratory facility located within the strictly secured Olympic Park. This laboratory, established and operated by the personnel of Antidoping Center, Moscow, has been authorized by the World Anti-Doping Agency (WADA) to conduct doping control analyses. The 4-floor building accommodated the most advanced analytical instrumentation and became a place of attraction for more than 50 Russian specialists and 25 foreign experts, including independent observers. In total, 2134 urine and 479 blood samples were delivered to the laboratory and analyzed during the Olympic Games (OG), and 403 urine and 108 blood samples - during the Paralympic Games (PG). The number of erythropoietin tests requested in urine was 946 and 166 at the OG and PG, respectively. Though included in the test distribution plan, a growth hormone analysis was cancelled by the Organizing Committee just before the Games. Several adverse analytical findings have been reported including pseudoephedrine (1 case), methylhexaneamine (4 cases), trimetazidine (1 case), dehydrochloromethyltestosterone (1 case), clostebol (1 case), and a designer stimulant N-ethyl-1-phenylbutan-2-amine (1 case). Copyright © 2014 John Wiley & Sons, Ltd.

Selenium and breast cancer risk: A prospective nested case-control study on serum selenium levels, smoking habits and overweight.

PubMed

Sandsveden, Malte; Manjer, Jonas

2017-11-01

Previous research has not been conclusive regarding the association between selenium (Se) and breast cancer. This study was conducted to clarify if there is an association between prediagnostic serum Se levels and breast cancer risk. A population based cohort, the Malmö Diet and Cancer Study, was used and linked with the Swedish cancer registry up to 31 December 2013. Our study included 1,186 women with breast cancer and an equal number of controls. Selenium levels were analysed from stored serum samples. The included individuals were divided into quartiles based on Se value and we compared breast cancer cases with controls using logistic regression yielding odds ratios (OR) with 95% confidence intervals. Serum Se was also analysed as a continuous variable regarding breast cancer risk. The analyses were adjusted for established risk factors and stratified on smoking status and body mass index (BMI). When comparing the highest Se quartile with the lowest, the adjusted OR for breast cancer was 0.98 (0.75-1.26). With selenium as a continuous variable the adjusted OR was 1.00 (1.00-1.01) per 10 ng/ml. When comparing the highest with the lowest Se quartile in women with BMI > 25 kg/m 2 the adjusted OR was 0.77 (0.53-1.14). We conclude that it is unlikely that prediagnostic serum selenium is overall associated with breast cancer risk and no modifying effect from BMI or smoking was seen. © 2017 UICC.

Physical activity, inflammatory biomarkers in gingival crevicular fluid and periodontitis.

PubMed

Sanders, Anne E; Slade, Gary D; Fitzsimmons, Tracy R; Bartold, Peter Mark

2009-05-01

To examine the associations of physical activity with interleukin 1-beta (IL-1beta), C-reactive protein (CRP) and periodontitis and to investigate whether any relationship between physical activity and inflammatory mediators differs between periodontitis cases and non-cases. In this population-based case control study of Australians aged 18+ years, dentists conducted oral epidemiologic examinations identifying cases with moderate or severe periodontitis and periodontally healthy controls. Gingival crevicular fluid samples collected during examinations were analysed for inflammatory biomarkers. Subject-completed questionnaires assessed leisure-time physical activity. Exposure odds ratios (ORs) were estimated in multivariable logistic regression models adjusting for periodontitis risk indicators. Of 751 subjects (359 cases, 392 controls), those meeting a prescribed threshold for leisure-time physical activity had lower adjusted odds of elevated IL-1beta: OR=0.69, (95% CI=0.50-0.94) and detectable CRP: OR=0.70 (0.50-0.98) than less active adults. Physical activity was not associated with periodontitis: OR=1.14 (0.80-1.62). Periodontitis modified the association between levels of physical activity and detectable CRP. Increasing quartiles of physically activity were associated with decreasing probability of detectable CRP, but the effect was limited to periodontitis cases and was not apparent among non-cases. Leisure-time physical activity may protect against an excessive inflammatory response in periodontitis.

Sleep disturbance in psoriasis - a case-controlled study.

PubMed

Jensen, P; Zachariae, C; Skov, L; Zachariae, R

2018-04-28

Sleep is essential for daytime functioning and health. Given the physical symptoms of psoriasis, a higher prevalence of sleep disorders could be expected. So far, the studies examining sleep disturbance in psoriasis have been of less-than-optimal methodological quality and with mixed results. We aimed to: 1) examine the prevalence of sleep disturbance in patients with plaque psoriasis compared to controls, 2) evaluate associations with health-related quality of life (HRQoL), and 3) examine possible disease-related predictors of disturbed sleep. We used a cross-sectional, case-controlled design. Participants included 179 consecutively recruited patients with plaque psoriasis and 105 controls. Measures included psoriasis severity (Psoriasis Area and Severity index [PASI]); HRQoL (Dermatology Life Quality Index [DLQI]); insomnia severity (Insomnia Severity Index [ISI]); sleep quality (Pittsburgh Sleep Quality Index [PSQI]); stress (Perceived Stress Scale [PSS]); Itch (Itch Severity Scale [ISS]); and depressive symptoms (Beck Depression Inventory [BDI]). Analyses included group comparisons and regression analyses to identify predictors of sleep disturbance. Twenty-five per cent of patients with psoriasis reported clinical insomnia (ISI > 15), compared with 10.5% of controls. In all, 53.9% of patients with psoriasis were poor sleepers (PSQI > 5), compared with 21.9% of controls. Itch was statistically significantly associated with all sleep-related outcomes. A higher proportion of patients with psoriasis suffer from poor sleep than controls from the general population. Itch was the main predictor of impaired sleep. Improved control of psoriasis with decreased itch may improve sleep disturbance in psoriasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Assessing Risk Factors for Problem Parenting: The Significance of Social Support.

ERIC Educational Resources Information Center

Turner, R. Jay; Avison, William R.

1985-01-01

Case comparison analyses were used to assess the power of social support, life stress, and personal control in distinguishing maladaptive mothers. Results indicate that social support, as experienced or perceived by the individual, effectively distinguishes among women who vary in their adaptation to the parenting role. (Author/BL)

Red and processed meat consumption and gastric cancer risk: a systematic review and meta-analysis

PubMed Central

Zhao, Zhanwei; Yin, Zifang; Zhao, Qingchuan

2017-01-01

The associations between red and processed meat consumption and gastric cancer risk have remained inconclusive. We performed a systematic review and meta-analysis to analyze these associations. We searched PubMed and EMBASE to identify studies published from inception through October 2016. Subtype analyses of gastric cancer (gastric cardia adenocarcinoma and gastric non-cardiac adenocarcinoma) and dose-response analyses were performed. We finally selected 42 eligible studies. The summary relative risks of highest versus lowest consumption were positive for case-control studies with 1.67 (1.36-2.05) for red meat and 1.76 (1.51-2.05) for processed meat, but negative for cohort studies with 1.14 (0.97-1.34) for red meat and 1.23 (0.98-1.55) for processed meat. Subtype analyses of cohort studies suggested null results for gastric cardia adenocarcinoma (red meat, P = 0.79; processed meat, P = 0.89) and gastric non-cardiac adenocarcinoma (red meat, P = 0.12; processed meat, P = 0.12). In conclusion, the present analysis suggested null results between red and processed meat consumption and gastric cancer risk in cohort studies, although case-control studies yielded positive associations. Further well-designed prospective studies are needed to validate these findings. PMID:28430644

Helicobacter Pylori “Test-and-Treat” Strategy for Management of Dyspepsia: A Comprehensive Review

PubMed Central

Gisbert, Javier P; Calvet, Xavier

2013-01-01

OBJECTIVES: Deciding on whether the Helicobacter pylori test-and-treat strategy is an appropriate diagnostic–therapeutic approach for patients with dyspepsia invites a series of questions. The aim present article addresses the test-and-treat strategy and attempts to provide practical conclusions for the clinician who diagnoses and treats patients with dyspepsia. METHODS: Bibliographical searches were performed in MEDLINE using the keywords Helicobacter pylori, test-and-treat, and dyspepsia. We focused mainly on data from randomized controlled trials (RCTs), systematic reviews, meta-analyses, cost-effectiveness analyses, and decision analyses. RESULTS: Several prospective studies and decision analyses support the use of the test-and-treat strategy, although we must be cautious when extrapolating the results from one geographical area to another. Many factors determine whether this strategy is appropriate in each particular area. The test-and-treat strategy will cure most cases of underlying peptic ulcer disease, prevent most potential cases of gastroduodenal disease, and yield symptomatic benefit in a minority of patients with functional dyspepsia. Future studies should be able to stratify dyspeptic patients according to their likelihood of improving after treatment of infection by H. pylori. CONCLUSIONS: The test-and-treat strategy will cure most cases of underlying peptic ulcer disease and prevent most potential cases of gastroduodenal disease. In addition, a minority of infected patients with functional dyspepsia will gain symptomatic benefit. Several prospective studies and decision analyses support the use of the test-and-treat strategy. The test-and-treat strategy is being reinforced by the accumulating data that support the increasingly accepted idea that “the only good H. pylori is a dead H. pylori”. PMID:23535826

Telomere length and genetics are independent colorectal tumour risk factors in an evaluation of biomarkers in normal bowel.

PubMed

Fernandez-Rozadilla, Ceres; Kartsonaki, Christiana; Woolley, Connor; McClellan, Michael; Whittington, Deb; Horgan, Gareth; Leedham, Simon; Kriaucionis, Skirmantas; East, James; Tomlinson, Ian

2018-03-06

Colorectal cancer (CRC) screening might be improved by using a measure of prior risk to modulate screening intensity or the faecal immunochemical test threshold. Intermediate molecular biomarkers could aid risk prediction by capturing both known and unknown risk factors. We sampled normal bowel mucosa from the proximal colon, distal colon and rectum of 317 individuals undergoing colonoscopy. We defined cases as having a personal history of colorectal polyp(s)/cancer, and controls as having no history of colorectal neoplasia. Molecular analyses were performed for: telomere length (TL); global methylation; and the expression of genes in molecular pathways associated with colorectal tumourigenesis. We also calculated a polygenic risk score (PRS) based on CRC susceptibility polymorphisms. Bowel TL was significantly longer in cases than controls, but was not associated with blood TL. PRS was significantly and independently higher in cases. Hypermethylation showed a suggestive association with case:control status. No gene or pathway was differentially expressed between cases and controls. Gene expression often varied considerably between bowel locations. PRS and bowel TL (but not blood TL) may be clinically-useful predictors of CRC risk. Sample collection to assess these biomarkers is feasible in clinical practice, especially where population screening uses flexible sigmoidoscopy or colonoscopy.

Analysis of risk factors for T. brucei rhodesiense sleeping sickness within villages in south-east Uganda

PubMed Central

Zoller, Thomas; Fèvre, Eric M; Welburn, Susan C; Odiit, Martin; Coleman, Paul G

2008-01-01

Background Sleeping sickness (HAT) caused by T.b. rhodesiense is a major veterinary and human public health problem in Uganda. Previous studies have investigated spatial risk factors for T.b. rhodesiense at large geographic scales, but none have properly investigated such risk factors at small scales, i.e. within affected villages. In the present work, we use a case-control methodology to analyse both behavioural and spatial risk factors for HAT in an endemic area. Methods The present study investigates behavioural and occupational risk factors for infection with HAT within villages using a questionnaire-based case-control study conducted in 17 villages endemic for HAT in SE Uganda, and spatial risk factors in 4 high risk villages. For the spatial analysis, the location of homesteads with one or more cases of HAT up to three years prior to the beginning of the study was compared to all non-case homesteads. Analysing spatial associations with respect to irregularly shaped geographical objects required the development of a new approach to geographical analysis in combination with a logistic regression model. Results The study was able to identify, among other behavioural risk factors, having a family member with a history of HAT (p = 0.001) as well as proximity of a homestead to a nearby wetland area (p < 0.001) as strong risk factors for infection. The novel method of analysing complex spatial interactions used in the study can be applied to a range of other diseases. Conclusion Spatial risk factors for HAT are maintained across geographical scales; this consistency is useful in the design of decision support tools for intervention and prevention of the disease. Familial aggregation of cases was confirmed for T. b. rhodesiense HAT in the study and probably results from shared behavioural and spatial risk factors amongmembers of a household. PMID:18590541

A case-control study of factors associated with HIV infection among black women.

PubMed

Forna, Fatu M; Fitzpatrick, Lisa; Adimora, Adaora A; McLellan-Lemal, Eleanor; Leone, Peter; Brooks, John T; Marks, Gary; Greenberg, Alan

2006-11-01

To identify social, behavioral and epidemiologic factors associated with HIV infection among HIV-infected and HIV-uninfected black women residing in North Carolina. A case-control study conducted in August 2004 in North Carolina. Cases were 18-40-year-old women with HIV infections diagnosed from 2003-2004. Controls were 18-40-yearold, HIV-negative heterosexually active women recruited from HIV testing sites. Five focus group discussions were also conducted with women not participating in the case-control study. Multivariate analyses of 31 cases and 101 controls showed that HIV-positive women were more likely to receive public assistance [adjusted odds ratio (aOR) 7.3; 95% confidence interval (CI) 2.1, 26.0], to report a history of genital herpes infection (aOR 10.6; 95% CI 2.4, 47.2), and were less likely to have discussed a variety of sexual and behavioral issues relevant to risk of HIV infection with their male partners (aOR 0.6; 95% CI 0.4, 0.8). Focus group participants indicated that financial and social demands created competing challenges for making HIV prevention a priority. Inadequate communication between black women and their sexual partners may create barriers to sexual and behavioral risk reduction. A multidimensional approach that addresses both biological factors such as herpes infection and socioeconomic factors may be needed to reduce HIV transmission in this population.

Hip fracture risk in relation to vitamin D supplementation and serum 25-hydroxyvitamin D levels: a systematic review and meta-analysis of randomised controlled trials and observational studies

PubMed Central

2010-01-01

Background Vitamin D supplementation for fracture prevention is widespread despite conflicting interpretation of relevant randomised controlled trial (RCT) evidence. This study summarises quantitatively the current evidence from RCTs and observational studies regarding vitamin D, parathyroid hormone (PTH) and hip fracture risk. Methods We undertook separate meta-analyses of RCTs examining vitamin D supplementation and hip fracture, and observational studies of serum vitamin D status (25-hydroxyvitamin D (25(OH)D) level), PTH and hip fracture. Results from RCTs were combined using the reported hazard ratios/relative risks (RR). Results from case-control studies were combined using the ratio of 25(OH)D and PTH measurements of hip fracture cases compared with controls. Original published studies of vitamin D, PTH and hip fracture were identified through PubMed and Web of Science databases, searches of reference lists and forward citations of key papers. Results The seven eligible RCTs identified showed no significant difference in hip fracture risk in those randomised to cholecalciferol or ergocalciferol supplementation versus placebo/control (RR = 1.13[95%CI 0.98-1.29]; 801 cases), with no significant difference between trials of <800 IU/day and ≥800 IU/day. The 17 identified case-control studies found 33% lower serum 25(OH)D levels in cases compared to controls, based on 1903 cases. This difference was significantly greater in studies with population-based compared to hospital-based controls (χ21 (heterogeneity) = 51.02, p < 0.001) and significant heterogeneity was present overall (χ216 (heterogeneity) = 137.9, p < 0.001). Serum PTH levels in hip fracture cases did not differ significantly from controls, based on ten case-control studies with 905 cases (χ29 (heterogeneity) = 149.68, p < 0.001). Conclusions Neither higher nor lower dose vitamin D supplementation prevented hip fracture. Randomised and observational data on vitamin D and hip fracture appear to differ. The reason for this is unclear; one possible explanation is uncontrolled confounding in observational studies. Post-fracture PTH levels are unrelated to hip fracture risk. PMID:20540727

The Family Investigation of Nephropathy and Diabetes (FIND): design and methods.

PubMed

Knowler, William C; Coresh, Josef; Elston, Robert C; Freedman, Barry I; Iyengar, Sudha K; Kimmel, Paul L; Olson, Jane M; Plaetke, Rosemarie; Sedor, John R; Seldin, Michael F

2005-01-01

The Family Investigation of Nephropathy and Diabetes (FIND) is a multicenter study designed to identify genetic determinants of diabetic nephropathy. It is conducted in eight U.S. clinical centers and a coordinating center, and with four ethnic groups (European Americans, African Americans, Mexican Americans, and American Indians). Two strategies are used to localize susceptibility genes: a family-based linkage study and a case-control study using mapping by admixture linkage disequilibrium (MALD). In the family-based study, probands with diabetic nephropathy are recruited with their parents and selected siblings. Linkage analyses will be conducted to identify chromosomal regions containing genes that influence the development of diabetic nephropathy or related quantitative traits such as serum creatinine concentration, urinary albumin excretion, and plasma glucose concentrations. Regions showing evidence of linkage will be examined further with both genetic linkage and association studies to identify genes that influence diabetic nephropathy or related traits. Two types of MALD studies are being done. One is a case-control study of unrelated individuals of Mexican American heritage in which both cases and controls have diabetes, but only the case has nephropathy. The other is a case-control study of African American patients with nephropathy (cases) and their spouses (controls) unaffected by diabetes and nephropathy; offspring are genotyped when available to provide haplotype data. Identification of genes that influence susceptibility to diabetic nephropathy will lead to a better understanding of how nephropathy develops. This should eventually lead to improved treatment and prevention.

Investigating the Role of Mitochondrial Haplogroups in Genetic Predisposition to Meningococcal Disease

PubMed Central

Salas, Antonio; Fachal, Laura; Marcos-Alonso, Sonia; Vega, Ana; Martinón-Torres, Federico

2009-01-01

Background and Aims Meningococcal disease remains one of the most important infectious causes of death in industrialized countries. The highly diverse clinical presentation and prognosis of Neisseria meningitidis infections are the result of complex host genetics and environmental interactions. We investigated whether mitochondrial genetic background contributes to meningococcal disease (MD) susceptibility. Methodology/Principal Findings Prospective controlled study was performed through a national research network on MD that includes 41 Spanish hospitals. Cases were 307 paediatric patients with confirmed MD, representing the largest series of MD patients analysed to date. Two independent sets of ethnicity-matched control samples (CG1 [N = 917]), and CG2 [N = 616]) were used for comparison. Cases and controls underwent mtDNA haplotyping of a selected set of 25 mtDNA SNPs (mtSNPs), some of them defining major European branches of the mtDNA phylogeny. In addition, 34 ancestry informative markers (AIMs) were genotyped in cases and CG2 in order to monitor potential hidden population stratification. Samples of known African, Native American and European ancestry (N = 711) were used as classification sets for the determination of ancestral membership of our MD patients. A total of 39 individuals were eliminated from the main statistical analyses (including fourteen gypsies) on the basis of either non-Spanish self-reported ancestry or the results of AIMs indicating a European membership lower than 95%. Association analysis of the remaining 268 cases against CG1 suggested an overrepresentation of the synonym mtSNP G11719A variant (Pearson's chi-square test; adjusted P-value = 0.0188; OR [95% CI] = 1.63 [1.22–2.18]). When cases were compared with CG2, the positive association could not be replicated. No positive association has been observed between haplogroup (hg) status of cases and CG1/CG2 and hg status of cases and several clinical variants. Conclusions We did not find evidence of association between mtSNPs and mtDNA hgs with MD after carefully monitoring the confounding effect of population sub-structure. MtDNA variability is particularly stratified in human populations owing to its low effective population size in comparison with autosomal markers and therefore, special care should be taken in the interpretation of seeming signals of positive associations in mtDNA case-control association studies. PMID:20019817

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/

Risk of transmission of sporadic Creutzfeldt-Jakob disease by surgical procedures: systematic reviews and quality of evidence.

PubMed

López, Fernando J García; Ruiz-Tovar, María; Almazán-Isla, Javier; Alcalde-Cabero, Enrique; Calero, Miguel; de Pedro-Cuesta, Jesús

2017-10-01

Sporadic Creutzfeldt-Jakob disease (sCJD) is potentially transmissible to humans. This study aimed to summarise and rate the quality of the evidence of the association between surgery and sCJD. Firstly, we conducted systematic reviews and meta-analyses of case-control studies with major surgical procedures as exposures under study. To assess quality of evidence, we used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Secondly, we conducted a systematic review of sCJD case reports after sharing neurosurgical instruments. Thirteen case-control studies met the inclusion criteria for the systematic review of case-control studies. sCJD was positively associated with heart surgery, heart and vascular surgery and eye surgery, negatively associated with tonsillectomy and appendectomy, and not associated with neurosurgery or unspecified major surgery. The overall quality of evidence was rated as very low. A single case-control study with a low risk of bias found a strong association between surgery conducted more than 20 years before disease onset and sCJD. Seven cases were described as potentially transmitted by reused neurosurgical instruments. The association between surgery and sCJD remains uncertain. Measures currently recommended for preventing sCJD transmission should be strongly maintained. Future studies should focus on the potential association between sCJD and surgery undergone a long time previously.

Productivity--a key to managing cost-per-case. Part 1.

PubMed

Orefice, J J; Jennings, M C

1983-08-01

Productivity and productivity management are critical to effective case-mix management. Case-mix management expands on traditional productivity management to include the relationship between such intermediate products as patient days, tests and meals, and the ultimate end product, the case. As hospitals search to increase the profitability of specific case types, they must focus on two critical productivity control points. First, they must examine length of stay and ancillary utilization as one level of productivity. Then they must turn to more traditional analyses and review departmental productivity in the production of the intermediate products. No case-mix management system is complete unless it focuses on both of these critical relationships. Part two of this article will explore performance reporting and its role in managing both productivity and case mix.

Analysis of copy number variation in Alzheimer's disease in a cohort of clinically characterized and neuropathologically verified individuals.

PubMed

Swaminathan, Shanker; Huentelman, Matthew J; Corneveaux, Jason J; Myers, Amanda J; Faber, Kelley M; Foroud, Tatiana; Mayeux, Richard; Shen, Li; Kim, Sungeun; Turk, Mari; Hardy, John; Reiman, Eric M; Saykin, Andrew J

2012-01-01

Copy number variations (CNVs) are genomic regions that have added (duplications) or deleted (deletions) genetic material. They may overlap genes affecting their function and have been shown to be associated with disease. We previously investigated the role of CNVs in late-onset Alzheimer's disease (AD) and mild cognitive impairment using Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Institute of Aging-Late Onset AD/National Cell Repository for AD (NIA-LOAD/NCRAD) Family Study participants, and identified a number of genes overlapped by CNV calls. To confirm the findings and identify other potential candidate regions, we analyzed array data from a unique cohort of 1617 Caucasian participants (1022 AD cases and 595 controls) who were clinically characterized and whose diagnosis was neuropathologically verified. All DNA samples were extracted from brain tissue. CNV calls were generated and subjected to quality control (QC). 728 cases and 438 controls who passed all QC measures were included in case/control association analyses including candidate gene and genome-wide approaches. Rates of deletions and duplications did not significantly differ between cases and controls. Case-control association identified a number of previously reported regions (CHRFAM7A, RELN and DOPEY2) as well as a new gene (HLA-DRA). Meta-analysis of CHRFAM7A indicated a significant association of the gene with AD and/or MCI risk (P = 0.006, odds ratio = 3.986 (95% confidence interval 1.490-10.667)). A novel APP gene duplication was observed in one case sample. Further investigation of the identified genes in independent and larger samples is warranted.

Association between rs3087243 and rs231775 polymorphism within the cytotoxic T-lymphocyte antigen 4 gene and Graves' disease: a case/control study combined with meta-analyses

PubMed Central

Dai, Yu; Zeng, Tianshu; Xiao, Fei; Chen, Lulu; Kong, Wen

2017-01-01

We conducted a case/control study to assess the impact of SNP rs3087243 and rs231775 within the CTLA4 gene, on the susceptibility to Graves' disease (GD) in a Chinese Han dataset (271 cases and 298 controls). The frequency of G allele for rs3087243 and rs231775 was observed to be significantly higher in subjects with GD than in control subjects (p = 0.005 and p = 0.000, respectively). After logistic regression analysis, a significant association was detected between SNP rs3087243 and GD in the additive and recessive models. Similarly, association for the SNP rs231775 could also be detected in the additive model, dominant model and recessive model. A meta-analysis, including 27 published datasets along with the current dataset, was performed to further confirm the association. Consistent with our case/control results, rs3087243 and rs231775 showed a significant association with GD in all genetic models. Of note, ethnic stratification revealed that these two SNPs were associated with susceptibility to GD in populations of both Asian and European descent. In conclusion, our data support that the rs3087243 and rs231775 polymorphisms within the CTLA4 gene confer genetic susceptibility to GD. PMID:29299173

[The analyse of telephone follow-up affecting the compliance of sublingual desensitization treatment to allergic rhinitis patients].

PubMed

Cui, Long; Wang, Zhinan; Xu, Zhongqiang; Xia, Zhongfang; Zhang, Yamin; Huang, Fang

2011-04-01

To analyze the compliance of sublingual desensitization used in allergic rhinitis patients by telephone follow up, and to discuss the influencing factor associate with medicine pause. One hundred and thirty-two patients of allergic rhinitis were randomly divided into two groups, 53 cases was in the control group, 79 cases was in telephone follow up group for a period of 6 months of observation. Sublingual desensitization treatment for 6 months, 28/53 cases of control group were compliance, 25/53 cases were loss, and compliance rate was 52.8%; 17/27 cases of follow-up group A were compliance, 10/27 cases were loss, and compliance rate was 63.0%; 21/28 cases of follow-up group B were compliance, 7/28 cases were loss, and compliance rate was 75.0%; 22/24 of follow-up group C were compliance, 2/24 cases were loss, and compliance rate was 91.7% (P < 0.05). Significant difference was found in the 4th month after treatment (P < 0.01). Long-term treatment and cure were the main impact factors for compliance. Timely telephone follow-up education and guidance to patients could improve compliance of patients with sublingual desensitization.

Integration of DNA sample collection into a multi-site birth defects case-control study.

PubMed

Rasmussen, Sonja A; Lammer, Edward J; Shaw, Gary M; Finnell, Richard H; McGehee, Robert E; Gallagher, Margaret; Romitti, Paul A; Murray, Jeffrey C

2002-10-01

Advances in quantitative analysis and molecular genotyping have provided unprecedented opportunities to add biological sampling and genetic information to epidemiologic studies. The purpose of this article is to describe the incorporation of DNA sample collection into the National Birth Defects Prevention Study (NBDPS), an ongoing case-control study in an eight-state consortium with a primary goal to identify risk factors for birth defects. Babies with birth defects are identified through birth defects surveillance systems in the eight participating centers. Cases are infants with one or more of over 30 major birth defects. Controls are infants without defects from the same geographic area. Epidemiologic information is collected through an hour-long interview with mothers of both cases and controls. We added the collection of buccal cytobrush DNA samples for case-infants, control-infants, and their parents to this study. We describe here the methods by which the samples have been collected and processed, establishment of a centralized resource for DNA banking, and quality control, database management, access, informed consent, and confidentiality issues. Biological sampling and genetic analyses are important components to epidemiologic studies of birth defects aimed at identifying risk factors. The DNA specimens collected in this study can be used for detection of mutations, study of polymorphic variants that confer differential susceptibility to teratogens, and examination of interactions among genetic risk factors. Information on the methods used and issues faced by the NBDPS may be of value to others considering the addition of DNA sampling to epidemiologic studies.

Environmental and occupational risk factors for progressive supranuclear palsy: Case-control study.

PubMed

Litvan, Irene; Lees, Peter S J; Cunningham, Christopher R; Rai, Shesh N; Cambon, Alexander C; Standaert, David G; Marras, Connie; Juncos, Jorge; Riley, David; Reich, Stephen; Hall, Deborah; Kluger, Benzi; Bordelon, Yvette; Shprecher, David R

2016-05-01

The cause of progressive supranuclear palsy (PSP) is largely unknown. Based on evidence for impaired mitochondrial activity in PSP, we hypothesized that the disease may be related to exposure to environmental toxins, some of which are mitochondrial inhibitors. This multicenter case-control study included 284 incident PSP cases of 350 cases and 284 age-, sex-, and race-matched controls primarily from the same geographical areas. All subjects were administered standardized interviews to obtain data on demographics, residential history, and lifetime occupational history. An industrial hygienist and a toxicologist unaware of case status assessed occupational histories to estimate past exposure to metals, pesticides, organic solvents, and other chemicals. Cases and controls were similar on demographic factors. In unadjusted analyses, PSP was associated with lower education, lower income, more smoking pack-years, more years of drinking well water, more years living on a farm, more years living 1 mile from an agricultural region, more transportation jobs, and more jobs with exposure to metals in general. However, in adjusted models, only more years of drinking well water was significantly associated with PSP. There was an inverse association with having a college degree. We did not find evidence for a specific causative chemical exposure; higher number of years of drinking well water is a risk factor for PSP. This result remained significant after adjusting for income, smoking, education and occupational exposures. This is the first case-control study to demonstrate PSP is associated with environmental factors. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Bayesian Estimation of Pneumonia Etiology: Epidemiologic Considerations and Applications to the Pneumonia Etiology Research for Child Health Study.

PubMed

Deloria Knoll, Maria; Fu, Wei; Shi, Qiyuan; Prosperi, Christine; Wu, Zhenke; Hammitt, Laura L; Feikin, Daniel R; Baggett, Henry C; Howie, Stephen R C; Scott, J Anthony G; Murdoch, David R; Madhi, Shabir A; Thea, Donald M; Brooks, W Abdullah; Kotloff, Karen L; Li, Mengying; Park, Daniel E; Lin, Wenyi; Levine, Orin S; O'Brien, Katherine L; Zeger, Scott L

2017-06-15

In pneumonia, specimens are rarely obtained directly from the infection site, the lung, so the pathogen causing infection is determined indirectly from multiple tests on peripheral clinical specimens, which may have imperfect and uncertain sensitivity and specificity, so inference about the cause is complex. Analytic approaches have included expert review of case-only results, case-control logistic regression, latent class analysis, and attributable fraction, but each has serious limitations and none naturally integrate multiple test results. The Pneumonia Etiology Research for Child Health (PERCH) study required an analytic solution appropriate for a case-control design that could incorporate evidence from multiple specimens from cases and controls and that accounted for measurement error. We describe a Bayesian integrated approach we developed that combined and extended elements of attributable fraction and latent class analyses to meet some of these challenges and illustrate the advantage it confers regarding the challenges identified for other methods. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

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

Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France.

PubMed

Dauvilliers, Yves; Arnulf, Isabelle; Lecendreux, Michel; Monaca Charley, Christelle; Franco, Patricia; Drouot, Xavier; d'Ortho, Marie-Pia; Launois, Sandrine; Lignot, Séverine; Bourgin, Patrice; Nogues, Béatrice; Rey, Marc; Bayard, Sophie; Scholz, Sabine; Lavault, Sophie; Tubert-Bitter, Pascale; Saussier, Cristel; Pariente, Antoine

2013-08-01

An increased incidence of narcolepsy in children was detected in Scandinavian countries where pandemic H1N1 influenza ASO3-adjuvanted vaccine was used. A campaign of vaccination against pandemic H1N1 influenza was implemented in France using both ASO3-adjuvanted and non-adjuvanted vaccines. As part of a study considering all-type narcolepsy, we investigated the association between H1N1 vaccination and narcolepsy with cataplexy in children and adults compared with matched controls; and compared the phenotype of narcolepsy with cataplexy according to exposure to the H1N1 vaccination. Patients with narcolepsy-cataplexy were included from 14 expert centres in France. Date of diagnosis constituted the index date. Validation of cases was performed by independent experts using the Brighton collaboration criteria. Up to four controls were individually matched to cases according to age, gender and geographic location. A structured telephone interview was performed to collect information on medical history, past infections and vaccinations. Eighty-five cases with narcolepsy-cataplexy were included; 23 being further excluded regarding eligibility criteria. Of the 62 eligible cases, 59 (64% males, 57.6% children) could be matched with 135 control subjects. H1N1 vaccination was associated with narcolepsy-cataplexy with an odds ratio of 6.5 (2.1-19.9) in subjects aged<18 years, and 4.7 (1.6-13.9) in those aged 18 and over. Sensitivity analyses considering date of referral for diagnosis or the date of onset of symptoms as the index date gave similar results, as did analyses focusing only on exposure to ASO3-adjuvanted vaccine. Slight differences were found when comparing cases with narcolepsy-cataplexy exposed to H1N1 vaccination (n=32; mostly AS03-adjuvanted vaccine, n=28) to non-exposed cases (n=30), including shorter delay of diagnosis and a higher number of sleep onset rapid eye movement periods for exposed cases. No difference was found regarding history of infections. In this sub-analysis, H1N1 vaccination was strongly associated with an increased risk of narcolepsy-cataplexy in both children and adults in France. Even if, as in every observational study, the possibility that some biases participated in the association cannot be completely ruled out, the associations appeared robust to sensitivity analyses, and a specific analysis focusing on ASO3-adjuvanted vaccine found similar increase.

Effectiveness of rugby headgear in preventing soft tissue injuries to the head: a case-control and video cohort study

PubMed Central

Jones, S; Lyons, R; Evans, R; Newcombe, R; Nash, P; McCabe, M; Palmer, S

2004-01-01

Objective: To determine if headgear use by rugby players was associated with a reduced risk of head or facial laceration, abrasion, or fracture. Methods: An emergency department based case-control study in South Wales, UK, with cases being rugby players treated for superficial head and facial injuries and controls being their matched opponents during the game. A review of videos of the 41 games in the 1999 Rugby World Cup was also carried out to compare with the case-control study. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to measure association between exposure (headgear wearing) and outcome (head and facial injuries). Results: In the case-control study, 164 pairs were analysed, with headgear worn by 12.8% of cases and 21.3% of controls. Headgear use was associated with substantial but non-significant reductions in superficial head (OR = 0.43, 95% CI 0.13 to 1.19) and facial (OR = 0.57, 95% CI 0.21 to 1.46) injuries. The video study followed 547 players over 41 games, during which there were 47 bleeding injuries to the head. Headgear use significantly reduced the risk of bleeding head injury in forwards (OR = 0.14, 95% CI 0.01 to 0.99, p = 0.02), but not in backs. There was also a higher risk of facial injury among forwards, but this was not significant. Conclusions: The combined results suggest that headgear can prevent certain types of superficial head injuries in players at all levels of the game, but the evidence is strongest for superficial head injury in elite forwards. A randomised controlled trial would be the best way to study this further. PMID:15039251

ANTIOXIDANT VITAMINS AND THE RISK OF ENDOMETRIAL CANCER: A DOSE-RESPONSE META-ANALYSIS

PubMed Central

Bandera, Elisa V.; Gifkins, Dina M.; Moore, Dirk F.; McCullough, Marjorie L.; Kushi, Lawrence H.

2008-01-01

Antioxidant vitamins may reduce cancer risk by limiting oxidative DNA damage. To summarize and quantify the current epidemiologic evidence of an association between antioxidant vitamin intake and endometrial cancer we conducted a systematic literature review and meta-analysis. One cohort and 12 case-control studies presenting relevant risk estimates were identified by conducting bibliographical searches through June 2008. Dose-response meta-analyses were conducted for beta-carotene, vitamin C, and vitamin E from food sources. Intake from supplements was not considered in the meta-analyses due to the few studies that reported relevant information. Based on case-control data, the random-effects summary odds ratios (OR) were, for beta-carotene: 0.88 (95% CI: 0.79–0.98) per 1,000 mcg/1,000 kcal (I2: 77.7%; p <0.01); for vitamin C: 0.85 (95% CI: 0.73–0.98) per 50 mg / 1,000 kcal (I2: 66.1%; p <0.01); and, for vitamin E: 0.91 (95% CI: 0.84–0.99) per 5 mg / 1,000 kcal (I2: 0.0%; p:0.45). In contrast, the only prospective study identified provided little indication of an association. Although the current case-control data suggest an inverse relationship of endometrial cancer risk with dietary intakes of beta-carotene, vitamin C, and vitamin E from food sources, additional studies are needed, particularly cohort studies, to confirm an association. PMID:19083131

Risk of hematological malignancies among Chernobyl liquidators

PubMed Central

Kesminiene, Ausrele; Evrard, Anne-Sophie; Ivanov, Viktor K.; Malakhova, Irina V.; Kurtinaitis, Juozas; Stengrevics, Aivars; Tekkel, Mare; Anspaugh, Lynn R.; Bouville, André; Chekin, Sergei; Chumak, Vadim V.; Drozdovitch, Vladimir; Gapanovich, Vladimir; Golovanov, Ivan; Hubert, Phillip; Illichev, Sergei V.; Khait, Svetlana E.; Krjuchkov, Viktor P.; Maceika, Evaldas; Maksyoutov, Marat; Mirkhaidarov, Anatoly K.; Polyakov, Semion; Shchukina, Natalia; Tenet, Vanessa; Tserakhovich, Tatyana I.; Tsykalo, Aleksandr; Tukov, Aleksandr R.; Cardis, Elisabeth

2010-01-01

A case-control study of hematological malignancies was conducted among Chernobyl liquidators (accident recovery workers) from Belarus, Russia and Baltic countries in order to assess the effect of low-to-medium dose protracted radiation exposures on the relative risk of these diseases. The study was nested within cohorts of liquidators who had worked in 1986–87 around the Chernobyl plant. 117 cases (69 leukemia, 34 non-Hodgkin Lymphoma (NHL) and 14 other malignancies of lymphoid and hematopoietic tissue) and 481 matched controls were included in the study. Individual dose to the bone marrow and uncertainties were estimated for each subject. The main analyses were restricted to 70 cases (40 leukemia, 20 NHL and 10 other) and their 287 matched controls with reliable information on work in the Chernobyl area. Most subjects received very low doses (median 13 mGy). For all diagnoses combined, a significantly elevated OR was seen at doses of 200 mGy and above. The Excess Relative Risk (ERR) per 100 mGy was 0.60 (90% confidence interval (CI): −0.02, 2.35). The corresponding estimate for leukemia excluding chronic lymphoid leukemia (CLL) was 0.50 (90%CI −0.38, 5.7). It is slightly higher than, but statistically compatible with, those estimated from a-bomb survivors and recent low dose-rate studies. Although sensitivity analyses showed generally similar results, we cannot rule out the possibility that biases and uncertainties could have led to over or underestimation of the risk in this study. PMID:19138033

Cancer in first-degree relatives and risk of testicular cancer in Denmark

PubMed Central

Nordsborg, Rikke Baastrup; Meliker, Jaymie R.; Wohlfahrt, Jan; Melbye, Mads; Raaschou-Nielsen, Ole

2011-01-01

Familial aggregation of testicular cancer has been reported consistently, but it is less clear if there is any association between risk of testicular cancer and other cancers in the family. We conducted a population based case-control study to examine the relationship between risk of testicular cancer and 22 different cancers in first-degree relatives. We included 3297 cases of testicular cancer notified to the Danish Cancer Registry between 1991 and 2003. 6594 matched controls were selected from the Danish Civil Registration System, which also provided the identity of 40,104 first-degree relatives of case and controls. Familial cancer was identified by linkage to the Danish Cancer Registry, and we used conditional logistic regression to analyse whether cancer among first-degree relatives was associated with higher risk of testicular cancer. Rate ratio (RR) for testicular cancer was 4.63 (95% CI: 2.41–8.87) when a father, 8.30(95% CI: 3.81–18.10) when a brother and 5.23 (95% CI: 1.35–20.26) when a son had testicular cancer compared with no familial testicular cancer. Results were similar when analyses were stratified by histologic subtypes of testicular cancer. Familial Non-Hodgkin lymphoma and oesophageal cancer were associated with testicular cancer; however these may be chance findings. The familial aggregation of testicular and possibly other cancers may be explained by shared genes and/or shared environmental factors, but the mutual importance of each of these is difficult to determine. PMID:21207375

Living on a farm, contact with farm animals and pets, and childhood acute lymphoblastic leukemia: pooled and meta-analyses from the Childhood Leukemia International Consortium.

PubMed

Orsi, Laurent; Magnani, Corrado; Petridou, Eleni T; Dockerty, John D; Metayer, Catherine; Milne, Elizabeth; Bailey, Helen D; Dessypris, Nick; Kang, Alice Y; Wesseling, Catharina; Infante-Rivard, Claire; Wünsch-Filho, Victor; Mora, Ana M; Spector, Logan G; Clavel, Jacqueline

2018-06-01

The associations between childhood acute lymphoblastic leukemia (ALL) and several factors related to early stimulation of the immune system, that is, farm residence and regular contacts with farm animals (livestock, poultry) or pets in early childhood, were investigated using data from 13 case-control studies participating in the Childhood Leukemia International Consortium. The sample included 7847 ALL cases and 11,667 controls aged 1-14 years. In all studies, the data were obtained from case and control parents using standardized questionnaires. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Contact with livestock in the first year of life was inversely associated with ALL (OR = 0.65, 95% CI: 0.50, 0.85). Inverse associations were also observed for contact with dogs (OR = 0.92, 95% CI: 0.86, 0.99) and cats (OR = 0.87, 95% CI: 0.80, 0.94) in the first year of life. There was no evidence of a significant association with farm residence in the first year of life. The findings of these large pooled and meta-analyses add additional evidence to the hypothesis that regular contact with animals in early childhood is inversely associated with childhood ALL occurrence which is consistent with Greaves' delayed infection hypothesis. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Cumulative sum control charts for assessing performance in arterial surgery.

PubMed

Beiles, C Barry; Morton, Anthony P

2004-03-01

The Melbourne Vascular Surgical Association (Melbourne, Australia) undertakes surveillance of mortality following aortic aneurysm surgery, patency at discharge following infrainguinal bypass and stroke and death following carotid endarterectomy. Quality improvement protocol employing the Deming cycle requires that the system for performing surgery first be analysed and optimized. Then process and outcome data are collected and these data require careful analysis. There must be a mechanism so that the causes of unsatisfactory outcomes can be determined and a good feedback mechanism must exist so that good performance is acknowledged and unsatisfactory performance corrected. A simple method for analysing these data that detects changes in average outcome rates is available using cumulative sum statistical control charts. Data have been analysed both retrospectively from 1999 to 2001, and prospectively during 2002 using cumulative sum control methods. A pathway to deal with control chart signals has been developed. The standard of arterial surgery in Victoria, Australia, is high. In one case a safe and satisfactory outcome was achieved by following the pathway developed by the audit committee. Cumulative sum control charts are a simple and effective tool for the identification of variations in performance standards in arterial surgery. The establishment of a pathway to manage problem performance is a vital part of audit activity.

Effectiveness of 23-valent pneumococcal polysaccharide vaccine and seasonal influenza vaccine for pneumonia among the elderly - Selection of controls in a case-control study.

PubMed

Kondo, Kyoko; Suzuki, Kanzo; Washio, Masakazu; Ohfuji, Satoko; Fukushima, Wakaba; Maeda, Akiko; Hirota, Yoshio

2017-08-24

We conducted a case-control study to elucidate associations between pneumonia in elderly individuals and 23-valent pneumococcal polysaccharide vaccine (PPSV23) and seasonal influenza vaccine (influenza vaccine). Here, we examined selection of controls in our study using an analytic epidemiology approach. The study period was from October 1, 2009 through September 30, 2014. Cases comprised ≥65-year-old patients newly diagnosed with pneumonia. For every case with pneumonia, two patients with other diseases (one respiratory medicine, one non-respiratory medicine) who were sex-, age-, visit date- and visit hospital-matched were selected as controls. Odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for pneumonia were calculated using conditional logistic regression model. Similar analyses were also conducted based on the clinical department of controls. Analysis was conducted in 234 cases and 438 controls. Effectiveness of pneumococcal vaccination or influenza vaccination against pneumonia was not detected. Proportions of either vaccination in controls were greater among respiratory medicine (pneumococcal vaccine, 38%; influenza vaccine, 55%) than among non-respiratory medicine (23%; 48%). Analysis using controls restricted to respiratory medicine showed marginally significant effectiveness of pneumococcal vaccination (OR, 0.59; 95%CI, 0.34-1.03; P=0.064) and influenza vaccination (0.64; 0.40-1.04; 0.072). However, this effectiveness might have been overestimated by selection bias of controls, as pneumonia cases are not necessarily respiratory medicine patients. In the analysis using controls restricted to non-respiratory medicine, OR of pneumococcal vaccination for pneumonia was close to 1, presumably because the proportion of pneumococcal vaccination was higher in cases than in controls. Because pneumococcal vaccine was not routinely administered during the study period, differences in recommendations of vaccination by physician in different clinical departments might have greatly affected vaccination proportions. When we select controls, we should consider the background factors (underlying diseases, clinical department, etc.) which affect physicians' recommendation of vaccination. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

In Vitro Maturation in Women with vs. without Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis

PubMed Central

Siristatidis, Charalampos; Sergentanis, Theodoros N.; Vogiatzi, Paraskevi; Kanavidis, Prodromos; Chrelias, Charalampos; Papantoniou, Nikolaos; Psaltopoulou, Theodora

2015-01-01

Objective To evaluate in vitro maturation (IVM) in sub-fertile women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF), by comparing outcomes with a control group of non-PCOS. Study design A search strategy was developed for PubMed and studies reporting rates of the following outcomes (live birth; clinical pregnancy; implantation; cycle cancellation; oocyte maturation; oocyte fertilization; miscarriage) between patients with PCOS, PCO and controls undergoing IVM were deemed eligible. The review was conducted in accordance to the PRISMA guidelines and included studies quality was assessed through the Newcastle-Ottawa Quality scale. ORs with their corresponding 95% CIs were calculated for the main analysis and subgroup analyses were performed for PCOS cases vs. controls and PCOS vs. PCO cases. Alternative analyses were performed for live birth and clinical pregnancy, based on cycles and on women. Subgroup analyses for FSH stimulation, hCG priming and type of procedure (IVF/ICSI) were undertaken for all meta-analyses encompassing at least four study arms. Random effects models were used to calculate pooled effect estimates. Results Eleven studies were identified. A total of 268 PCOS patients (328 cycles), 100 PCO patients (110 cycles) and 440 controls (480 cycles) were included in the meta-analysis. A borderline trend towards higher birth rates among PCOS patients emerged (pooled OR = 1.74, 95%CI: 0.99–3.04) mainly reflected at the subgroup analysis vs. controls. Clinical pregnancy (pooled OR = 2.37, 95%CI: 1.53–3.68) and implantation rates (pooled OR = 1.73, 95%CI: 1.06–2.81) were higher, while cancellation rates lower (pooled OR = 0.18, 95%CI: 0.06-0.47) among PCOS vs. non-PCOS subjects; maturation and miscarriage rates did not differ between groups, while a borderline trend towards lower fertilization rates among PCOS patients was observed. Conclusion The present meta-analysis provides preliminary evidence on the effectiveness of IVM as a treatment option when offered in sub-fertile PCOS women, as the latter present at least as high outcome rates as those in non-PCOS. PMID:26241855

Geographic profiling as a novel spatial tool for targeting infectious disease control

PubMed Central

2011-01-01

Background Geographic profiling is a statistical tool originally developed in criminology to prioritise large lists of suspects in cases of serial crime. Here, we use two data sets - one historical and one modern - to show how it can be used to locate the sources of infectious disease. Results First, we re-analyse data from a classic epidemiological study, the 1854 London cholera outbreak. Using 321 disease sites as input, we evaluate the locations of 13 neighbourhood water pumps. The Broad Street pump - the outbreak's source- ranks first, situated in the top 0.2% of the geoprofile. We extend our study with an analysis of reported malaria cases in Cairo, Egypt, using 139 disease case locations to rank 59 mosquitogenic local water sources, seven of which tested positive for the vector Anopheles sergentii. Geographic profiling ranks six of these seven sites in positions 1-6, all in the top 2% of the geoprofile. In both analyses the method outperformed other measures of spatial central tendency. Conclusions We suggest that geographic profiling could form a useful component of integrated control strategies relating to a wide variety of infectious diseases, since evidence-based targeting of interventions is more efficient, environmentally friendly and cost-effective than untargeted intervention. PMID:21592339

A retrospective study of gastric dilatation and gastric dilatation and volvulus in working farm dogs in New Zealand.

PubMed

Hendriks, M M; Hill, K E; Cogger, N; Jones, B R; Cave, N J

2012-05-01

To present findings from a case series of gastric dilatation (GD) or gastric dilatation and volvulus (GDV) in working farm dogs in New Zealand that were examined at veterinary clinics, and to identify possible risk factors for GD or GDV in working farm dogs in New Zealand using a case-control study. This retrospective study included a case-series and a case-control study. The case series analysed information from 62 case records of GD or GDV in working farm dogs seen between August 2004 and September 2009 at 13 veterinary clinics throughout New Zealand. Cases were classified as GD or GDV if the diagnosis was confirmed by radiography, surgery or post-mortem examination. Details of history and treatment, as well as outcomes, were obtained for each case. For the case-control study, records of 41 working farm dogs with GD or GDV (cases) seen between April 2008 and April 2009, and 82 working farm dogs examined because of trauma over the same period and in the same 13 clinics (controls), were used to model the risk factors for GD or GDV. From the case-series study, 40/62 (65%) cases of GD or GDV that were examined and treated at the veterinary clinics returned to work. Of the 41 dogs where the gastric contents were recorded, 25 (61%) had predominantly food or bones in the stomach, and 26/27 dogs had a history of having eaten meat, bones or scavenged a carcass. The case-control study showed that the significant risk factors for GD or GDV, compared with control dogs presenting with trauma, were breed, age and season. The odds that a case of GD or GDV was a Huntaway, after adjusting for age and season, was 19 times higher than the odds a control was a Huntaway. Gender and bodyweight were not identified as risk factors. A high proportion of farm working dogs with GD or GDV were successfully treated by veterinarians. The risk of a case of GD or GDV being a Huntaway was significantly higher than for a dog presenting as a trauma case. However the influences of the season of the year, climatic factors and nutritional factors on the pathogenesis need to be identified before adequate preventative measures can be recommended.

Respiratory viruses in young South African children with acute lower respiratory infections and interactions with HIV.

PubMed

Annamalay, Alicia A; Abbott, Salome; Sikazwe, Chisha; Khoo, Siew-Kim; Bizzintino, Joelene; Zhang, Guicheng; Laing, Ingrid; Chidlow, Glenys R; Smith, David W; Gern, James; Goldblatt, Jack; Lehmann, Deborah; Green, Robin J; Le Souëf, Peter N

2016-08-01

Human rhinovirus (RV) is the most common respiratory virus and has been associated with frequent and severe acute lower respiratory infections (ALRI). The prevalence of RV species among HIV-infected children in South Africa is unknown. To describe the prevalence of respiratory viruses, including RV species, associated with HIV status and other clinical symptoms in children less than two years of age with and without ALRI in Pretoria, South Africa. Nasopharyngeal aspirates were collected from 105 hospitalized ALRI cases and 53 non-ALRI controls less than two years of age. HIV status was determined. Common respiratory viruses were identified by PCR, and RV species and genotypes were identified by semi-nested PCR, sequencing and phylogenetic tree analyses. Respiratory viruses were more common among ALRI cases than controls (83.8% vs. 69.2%; p=0.041). RV was the most commonly identified virus in cases with pneumonia (45.6%) or bronchiolitis (52.1%), regardless of HIV status, as well as in controls (39.6%). RV-A was identified in 26.7% of cases and 15.1% of controls while RV-C was identified in 21.0% of cases and 18.9% of controls. HIV-infected children were more likely to be diagnosed with pneumonia than bronchiolitis (p<0.01). RSV was not identified in any HIV-infected cases (n=15) compared with 30.6% of HIV-uninfected cases (n=85, p=0.013), and was identified more frequently in bronchiolitis than in pneumonia cases (43.8% vs. 12.3%; p<0.01). RV-A and RV-C are endemic in South African children and HIV infection may be protective against RSV and bronchiolitis. Copyright © 2016 Elsevier B.V. All rights reserved.

Known glioma risk loci are associated with glioma with a family history of brain tumours -- a case-control gene association study.

PubMed

Melin, Beatrice; Dahlin, Anna M; Andersson, Ulrika; Wang, Zhaoming; Henriksson, Roger; Hallmans, Göran; Bondy, Melissa L; Johansen, Christoffer; Feychting, Maria; Ahlbom, Anders; Kitahara, Cari M; Wang, Sophia S; Ruder, Avima M; Carreón, Tania; Butler, Mary Ann; Inskip, Peter D; Purdue, Mark; Hsing, Ann W; Mechanic, Leah; Gillanders, Elizabeth; Yeager, Meredith; Linet, Martha; Chanock, Stephen J; Hartge, Patricia; Rajaraman, Preetha

2013-05-15

Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive family history of brain tumours, defined as having at least one first- or second-degree relative with a history of brain tumour, are associated with known glioma risk loci. One thousand four hundred and thirty-one glioma cases and 2,868 cancer-free controls were identified from four case-control studies and two prospective cohorts from USA, Sweden and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain tumours (n = 104) and control subjects free of glioma at baseline, three of seven SNPs were associated with glioma risk: rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B) and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically significantly associated with glioma risk, rs6010620 (ORtrend for the minor (A) allele, 0.39; 95% CI: 0.25-0.61; Bonferroni adjusted ptrend , 1.7 × 10(-4) ). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk of glioma when restricting to cases with family history of brain tumours. These findings require confirmation in further studies with a larger number of glioma cases with a family history of brain tumours. Copyright © 2012 UICC.

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.

Neural control and transient analysis of the LCL-type resonant converter

NASA Astrophysics Data System (ADS)

Zouggar, S.; Nait Charif, H.; Azizi, M.

2000-07-01

This paper proposes a generalised inverse learning structure to control the LCL converter. A feedforward neural network is trained to act as an inverse model of the LCL converter then both are cascaded such that the composed system results in an identity mapping between desired response and the LCL output voltage. Using the large signal model, we analyse the transient output response of the controlled LCL converter in the case of large variation of the load. The simulation results show the efficiency of using neural networks to regulate the LCL converter.

Resolvent analysis of suboptimal control for turbulent skin friction drag reduction

NASA Astrophysics Data System (ADS)

Nakashima, Satoshi; Fukagata, Koji; Luhar, Mitul

2017-11-01

We study the drag reduction mechanisms of suboptimal control (Lee et al. 1998) via the resolvent formulation developed by McKeon and Sharma (2010). Under this formulation, the nonlinear term in the Navier-Stokes equations is regarded as a forcing which acts upon the linear dynamics to output a velocity response across Fourier space. This analysis enables targeted analyses of the effects of the control on modes resembling dynamically important coherent structures such as the near-wall (NW) cycle. Suboptimal control generates blowing and suction at the wall that is proportional to the streamwise (Case ST) or spanwise (Case SP) wall shear-stress, with the magnitude of blowing and suction being a design parameter. Both Case ST and SP can suppress resolvent modes resembling the NW cycle. However, for Case ST, the analysis reveals that the control leads to substantial increase in amplification for structures that are long in the spanwise direction. High actuation of such energetic spanwise structures was confirmed by conducting limited direct numerical simulations. In addition to the study of modes resembling the NW cycle, we will discuss modes of varying propagating speed and wavelength to provide insight into the effects of suboptimal control across spectral space. This work was supported through Grant-in-Aid for Scientific Research (C) (No. 25420129) by Japan Society for the Promotion of Science (JSPS).

Modifiable risk factors of hypertension: A hospital-based case-control study from Kerala, India.

PubMed

Pilakkadavath, Zarin; Shaffi, Muhammed

2016-01-01

Hypertension is a major cause of cardiovascular morbidity and mortality in Kerala. Excess dietary salt, low dietary potassium, overweight and obesity, physical inactivity, excess alcohol, smoking, socioeconomic status, psychosocial stressors, and diabetes are considered as modifiable risk factors for hypertension. To estimate and compare the distribution of modifiable risk factors among hypertensive (cases) and nonhypertensive (controls) patients and to estimate the effect relationship of risk factors. Age- and sex-matched case-control study was conducted in a tertiary care hospital in Kerala using a pretested interviewer-administered structured questionnaire based on the WHO STEPS instrument for chronic disease risk factor surveillance. Bivariate and multiple logistic regression analyses were done. A total of 296 subjects were included in the study. The mean age of study sample was 50.13 years. All modifiable risk factors studied vis-ΰ-vis obesity, lack of physical activity, inadequate fruits and vegetable intake, diabetes, smoking, and alcohol use were significantly different in proportion among cases and controls. Obesity, lack of physical activity, smoking, and diabetes were found to be significant risk factors for hypertension after adjusting for other risk factors. Hypertension is strongly driven by a set of modifiable risk factors. Massive public awareness campaign targeting risk factors is essential in controlling hypertension in Kerala, especially focusing on physical exercise and control of diabetes, obesity, and on quitting smoking.

A case-control study on risk factors of breast cancer in Han Chinese women.

PubMed

Liu, Li-Yuan; Wang, Fei; Cui, Shu-De; Tian, Fu-Guo; Fan, Zhi-Min; Geng, Cui-Zhi; Cao, Xu-Chen; Yang, Zhen-Lin; Wang, Xiang; Liang, Hong; Wang, Shu; Jiang, Hong-Chuan; Duan, Xue-Ning; Wang, Hai-Bo; Li, Guo-Lou; Wang, Qi-Tang; Zhang, Jian-Guo; Jin, Feng; Tang, Jin-Hai; Li, Liang; Zhu, Shi-Guang; Zuo, Wen-Shu; Yu, Li-Xiang; Xiang, Yu-Juan; Zhou, Fei; Li, Liang; Zhang, Qiang; Fu, Qin-Ye; Ma, Zhong-Bing; Gao, De-Zong; Li, Yu-Yang; Liu, Lu; Ye, Chun-Miao; Wang, Yong-Jiu; Zhou, Wen-Zhong; Yu, Zhi-Gang

2017-11-14

This study aimed to investigate risk factors associated with breast cancer among Han Chinese women in northern and eastern China. A matched case-control study involving 1489 patients with breast cancer and 1489 controls was conducted across 21 hospitals in 11 provinces in China, from April 2012 to April 2013. We developed a structured questionnaire to record information from face-to-face interviews with participants. Student's t-tests, Pearson's chi-square tests, and univariate and multivariate conditional logistic regression analyses were used to identify variables with significant differences between the case and control groups. Ten variables were identified (P < 0.05): location, economic status, waist-to-hip ratio, menopause, family history of breast cancer, present life satisfaction, sleep satisfaction, milk products, behavior prevention scores, and awareness of breast cancer. We identified a comprehensive range of factors related to breast cancer, among which several manageable factors may contribute to breast cancer prevention. Further prospective studies concerning psychological interventions, sleep regulation, health guidance, and physical exercise are required. A screening model for high-risk populations should be put on the agenda.

Reprint of: Relationship between cataract severity and socioeconomic status.

PubMed

Wesolosky, Jason D; Rudnisky, Christopher J

2015-06-01

To determine the relationship between cataract severity and socioeconomic status (SES). Retrospective, observational case series. A total of 1350 eyes underwent phacoemulsification cataract extraction by a single surgeon using an Alcon Infiniti system. Cataract severity was measured using phaco time in seconds. SES was measured using area-level aggregate census data: median income, education, proportion of common-law couples, and employment rate. Preoperative best corrected visual acuity was obtained and converted to logarithm of the minimum angle of resolution values. For patients undergoing bilateral surgery, the generalized estimating equation was used to account for the correlation between eyes. Univariate analyses were performed using simple regression, and multivariate analyses were performed to account for variables with significant relationships (p < 0.05) on univariate testing. Sensitivity analyses were performed to assess the effect of including patient age in the controlled analyses. Multivariate analyses demonstrated that cataracts were more severe when the median income was lower (p = 0.001) and the proportion of common-law couples living in a patient's community (p = 0.012) and the unemployment rate (p = 0.002) were higher. These associations persisted even when controlling for patient age. Patients of lower SES have more severe cataracts. Copyright © 2015. Published by Elsevier Inc.

Nonsyndromic cleft lip with or without cleft palate: Increased burden of rare variants within Gremlin-1, a component of the bone morphogenetic protein 4 pathway.

PubMed

Al Chawa, Taofik; Ludwig, Kerstin U; Fier, Heide; Pötzsch, Bernd; Reich, Rudolf H; Schmidt, Gül; Braumann, Bert; Daratsianos, Nikolaos; Böhmer, Anne C; Schuencke, Hannah; Alblas, Margrieta; Fricker, Nadine; Hoffmann, Per; Knapp, Michael; Lange, Christoph; Nöthen, Markus M; Mangold, Elisabeth

2014-06-01

The genes Gremlin-1 (GREM1) and Noggin (NOG) are components of the bone morphogenetic protein 4 pathway, which has been implicated in craniofacial development. Both genes map to recently identified susceptibility loci (chromosomal region 15q13, 17q22) for nonsyndromic cleft lip with or without cleft palate (nsCL/P). The aim of the present study was to determine whether rare variants in either gene are implicated in nsCL/P etiology. The complete coding regions, untranslated regions, and splice sites of GREM1 and NOG were sequenced in 96 nsCL/P patients and 96 controls of Central European ethnicity. Three burden and four nonburden tests were performed. Statistically significant results were followed up in a second case-control sample (n = 96, respectively). For rare variants observed in cases, segregation analyses were performed. In NOG, four rare sequence variants (minor allele frequency < 1%) were identified. Here, burden and nonburden analyses generated nonsignificant results. In GREM1, 33 variants were identified, 15 of which were rare. Of these, five were novel. Significant p-values were generated in three nonburden analyses. Segregation analyses revealed incomplete penetrance for all variants investigated. Our study did not provide support for NOG being the causal gene at 17q22. However, the observation of a significant excess of rare variants in GREM1 supports the hypothesis that this is the causal gene at chr. 15q13. Because no single causal variant was identified, future sequencing analyses of GREM1 should involve larger samples and the investigation of regulatory elements. © 2014 Wiley Periodicals, Inc.

Escherichia coli O157:H7 outbreak linked to salami, British Columbia, Canada, 1999.

PubMed Central

MacDonald, D. M.; Fyfe, M.; Paccagnella, A.; Trinidad, A.; Louie, K.; Patrick, D.

2004-01-01

An outbreak of E. coli O157:H7 infections was identified in November 1999 with a fivefold increase in the occurrence of laboratory-confirmed cases of E. coli O157:H7 infection. A matched case-control study was conducted. Samples of food from cases and from retailers were analysed for the presence of E. coli O157:H7. A total of 143 cases were identified over a 12-week period with the same pulsed-field gel electrophoresis (PFGE) pattern. The case-control study found that Company A salami was significantly associated with illness (Mantel-Haenszel matched odds ratio 10.0%, 95% CI 1.4-434, P=0.01). Company A salami tested positive for E. coli O157:H7 and isolates had the same PFGE pattern as case isolates. An immediate voluntary national recall of Company A dry fermented meat products took place. Findings from the investigation of this outbreak suggest that the hold-and-test option may not be adequate to prevent shiga-toxigenic Escherichia coli (STEC) infection in salami consumers. PMID:15061503

Indoor radon and childhood leukaemia.

PubMed

Raaschou-Nielsen, Ole

2008-01-01

This paper summarises the epidemiological literature on domestic exposure to radon and risk for childhood leukaemia. The results of 12 ecological studies show a consistent pattern of higher incidence and mortality rates for childhood leukaemia in areas with higher average indoor radon concentrations. Although the results of such studies are useful to generate hypotheses, they must be interpreted with caution, as the data were aggregated and analysed for geographical areas and not for individuals. The seven available case-control studies of childhood leukaemia with measurement of radon concentrations in the residences of cases and controls gave mixed results, however, with some indication of a weak (relative risk < 2) association with acute lymphoblastic leukaemia. The epidemiological evidence to date suggests that an association between indoor exposure to radon and childhood leukaemia might exist, but is weak. More case-control studies are needed, with sufficient statistical power to detect weak associations and based on designs and methods that minimise misclassification of exposure and provide a high participation rate and low potential selection bias.

[A case-control study on the risk factors of esophageal cancer in Linzhou].

PubMed

Lu, J; Lian, S; Sun, X; Zhang, Z; Dai, D; Li, B; Cheng, L; Wei, J; Duan, W

2000-12-01

To explore the characteristics of prevalence and influencing factors on the genesis of esophageal cancer. A population-based 1:1 matched case-control study was conducted in Linzhou. A total number of 352 pairs of cases and controls matched on sex, age and neighborhoods. Data was analysed by SAS software to calculate the odds ratio of and to evaluate the relative risks. It was found that lower socio-economic status, environmental pollution around the residential areas, lampblack in room, lower body mass index (BMI), more pickled food intake, cigarette smoking, alcoholic drinking, vigor mental-trauma and depression were risk factors of esophageal cancer. It also showed that the subjects having had history of upper digestive tract operation, dysplasia of esophagus and family history of carcinoma markedly increased the risks of developing esophageal cancer. Esophageal cancer seemed to be resulted from the combination of genetic and environmental factor, hence called for of medical surveillance and comprehensive prevention.

[Risk factors associated with non-alcoholic fatty liver disease: a case-control study].

PubMed

Caballería, Llorenç; Arteaga, Ingrid; Pera, Guillem; Rodríguez, Lluís; Alumà, Alba; Auladell, Maria Antònia; Torán, Pere

2013-09-21

To establish the factors associated with the presence of non-alcoholic fatty liver disease (NAFLD) and evaluate the influence of each component constituting the metabolic syndrome (MS) and the risk of developing NAFLD. We performed a multicenter, population-based, observational, analytical study of cases and controls. A case was defined as any patient fulfilling the inclusion criteria and presenting NAFLD by abdominal echography for any reason. A control was randomly selected for each case, from the same health center and of the same age and sex. All the cases underwent anamnesis, physical examination, complete biochemical analyses and determination of MS according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. All the controls also underwent an abdominal echography. We included 327 cases and 377 controls with a mean age of 56 ± 12 years for the cases and of 55 ± 13 years for the controls (range: 17 and 80 years); 52.0% of the cases were males and 49.1% of males were controls. The risk factors associated with NAFLD were obesity (odds ratio [OR] 3.82, 95% confidence interval [95% CI] 2.19-6.66), MS (OR 1.73, 95% CI 1.09-2.75), insulin resistance (OR 3.65, 95% CI 2.18-6.12), and an increase in alanine aminotransferase (ALT) (OR 4.72, 95% CI 2.58-8.61) and gamma glutamyl transferase values (GGT) (OR 1.95, 95% CI 1.14-3.34). The components of the MS best predicting NAFLD were hyperglycemia (OR 1.65, 95% CI1.06-2.56) and triglyceride values (OR 1.75, 95% CI1.13-2.72). The independent variables associated with NAFLD were obesity, insulin resistance and elevated ALT and GGT. The components of MS best predicting NAFLD were hyperglycemia and an increase in triglyceride values. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Changes to Hospital Inpatient Volume After Newspaper Reporting of Medical Errors.

PubMed

Fukuda, Haruhisa

2017-06-30

The aim of this study was to investigate the influence of medical error case reporting by national newspapers on inpatient volume at acute care hospitals. A case-control study was conducted using the article databases of 3 major Japanese newspapers with nationwide circulation between fiscal years 2012 and 2013. Data on inpatient volume at acute care hospitals were obtained from a Japanese government survey between fiscal years 2011 and 2014. Panel data were constructed and analyzed using a difference-in-differences design. Acute care hospitals in Japan. Hospitals named in articles that included the terms "medical error" and "hospital" were designated case hospitals, which were matched with control hospitals using corresponding locations, nurse-to-patient ratios, and bed numbers. Medical error case reporting in newspapers. Changes to hospital inpatient volume after error reports. The sample comprised 40 case hospitals and 40 control hospitals. Difference-in-differences analyses indicated that newspaper reporting of medical errors was not significantly associated (P = 0.122) with overall inpatient volume. Medical error case reporting by newspapers showed no influence on inpatient volume. Hospitals therefore have little incentive to respond adequately and proactively to medical errors. There may be a need for government intervention to improve the posterror response and encourage better health care safety.

Exome sequence analysis and follow up genotyping implicates rare ULK1 variants to be involved in susceptibility to schizophrenia

PubMed Central

Al Eissa, Mariam M.; Fiorentino, Alessia; Sharp, Sally I.; O'Brien, Niamh L.; Wolfe, Kate; Giaroli, Giovanni; Curtis, David; Bass, Nicholas J.

2017-01-01

Summary Schizophrenia (SCZ) is a severe, highly heritable psychiatric disorder. Elucidation of the genetic architecture of the disorder will facilitate greater understanding of the altered underlying neurobiological mechanisms. The aim of this study was to identify likely aetiological variants in subjects affected with SCZ. Exome sequence data from a SCZ cas–control sample from Sweden was analysed for likely aetiological variants using a weighted burden test. Suggestive evidence implicated the UNC‐51‐like kinase (ULK1) gene, and it was observed that four rare variants that were more common in the Swedish SCZ cases were also more common in UK10K SCZ cases, as compared to obesity cases. These three missense variants and one intronic variant were genotyped in the University College London cohort of 1304 SCZ cases and 1348 ethnically matched controls. All four variants were more common in the SCZ cases than controls and combining them produced a result significant at P = 0.02. The results presented here demonstrate the importance of following up exome sequencing studies using additional datasets. The roles of ULK1 in autophagy and mTOR signalling strengthen the case that these pathways may be important in the pathophysiology of SCZ. The findings reported here await independent replication. PMID:29148569

Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African Americans.

PubMed

Reitz, Christiane; Jun, Gyungah; Naj, Adam; Rajbhandary, Ruchita; Vardarajan, Badri Narayan; 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; 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; Schellenberg, Gerard D; Mayeux, Richard

2013-04-10

Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment. To identify genetic loci associated with late-onset Alzheimer disease in African Americans. The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance-weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci. Presence of Alzheimer disease according to standardized criteria. Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10(-9)), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8 < D' < 0.9). The effect size for the SNP in ABCA7 was comparable with that of the APOE ϵ4-determining SNP rs429358 (allele = C; frequency, 0.30 cases and 0.18 controls; OR, 2.31 [95% CI, 2.19-2.42]; P = 5.5 × 10(-47)). Several loci previously associated with Alzheimer disease but not reaching significance in genome-wide analyses were replicated in gene-based analyses accounting for linkage disequilibrium between markers and correcting for number of tests performed per gene (CR1, BIN1, EPHA1, CD33; 0.0005 < empirical P < .001). In this meta-analysis of data from African American participants, Alzheimer disease was significantly associated with variants in ABCA7 and with other genes that have been associated with Alzheimer disease in individuals of European ancestry. Replication and functional validation of this finding is needed before this information is used in clinical settings.

Analytical report of the 2016 dengue outbreak in Córdoba city, Argentina.

PubMed

Rotela, Camilo; Lopez, Laura; Frías Céspedes, María; Barbas, Gabriela; Lighezzolo, Andrés; Porcasi, Ximena; Lanfri, Mario A; Scavuzzo, Carlos M; Gorla, David E

2017-11-06

After elimination of the Aedes aegypti vector in South America in the 1960s, dengue outbreaks started to reoccur during the 1990s; strongly in Argentina since 1998. In 2016, Córdoba City had the largest dengue outbreak in its history. In this article we report this outbreak including spatio-temporal analysis of cases and vectors in the city. A total of 653 dengue cases were recorded by the laboratory-based dengue surveillance system and georeferenced by their residential addresses. Case maps were generated from the epidemiological week 1 (beginning of January) to week 19 (mid-May). Dengue outbreak temporal evolution was analysed globally and three specific, high-incidence zones were detected using Knox analysis to characterising its spatio-temporal attributes. Field and remotely sensed data were collected and analysed in real time and a vector presence map based on the MaxEnt approach was generated to define hotspots, towards which the pesticide- based strategy was then targeted. The recorded pattern of cases evolution within the community suggests that dengue control measures should be improved.

Habitual Consumption of Soy Products and Risk of Nasopharyngeal Carcinoma in Chinese Adults: A Case-Control Study

PubMed Central

Liu, Yuan-ting; Fan, Yu-ying; Xu, Chun-hua; Lin, Xiao-ling; Lu, Yun-kai; Zhang, Xing-lan; Zhang, Cai-xia; Chen, Yu-ming

2013-01-01

Background and Objectives Many studies have shown a negative association between the consumption of soy products and the risk of some cancers, but little is known about the effect of soy consumption on nasopharyngeal carcinoma. We assessed the association between the consumption of soy products on nasopharyngeal carcinoma risk in Chinese individuals. Methods This case-control study included 600 (448 males and 152 females) incident cases of nasopharyngeal carcinoma, and an equal number of controls, matched according to gender, age (± 3 y) and household type to the nasopharyngeal carcinoma cases. All subjects were recruited from hospitals in Guangzhou, China. A face-to-face interview was conducted with each study individual to collect general information and habitual dietary intake using a 78-item quantitative food-frequency questionnaire. Odds ratios and their 95% confidence intervals were estimated using conditional logistic regression analyses. Results The median intakes of soy foods (in protein) were 0.5/0.5, 1.4/1.7, 2.7/3.3 and 6.1/7.7 (male/female) g/d in the quartiles 1 to 4. Both univariate and multivariate analyses showed no significant association between the consumption of soy proteins or soy isoflavones and the risk of nasopharyngeal carcinoma. The adjusted odds ratios (95% confidence intervals) between extreme quartiles were 0.97 (0.66-1.45) for soy proteins and 0.97 (0.66-1.42) for total isoflavones. Null associations were also observed between intake of the individual isoflavones daidzein, genistein and glycitein and NPC risk, with adjusted odds ratios for the extreme quartiles ranging between 0.73 and 1.23. Conclusion Habitual consumption of soy products had no significant effect on the risk of nasopharyngeal carcinoma in Chinese adults with a relatively low intake. PMID:24155974

Fibromyalgia and seizures.

PubMed

Tatum, William O; Langston, Michael E; Acton, Emily K

2016-06-01

The purpose of this case-matched study was to determine how frequently fibromyalgia is associated with different paroxysmal neurological disorders and explore the utility of fibromyalgia as a predictor for the diagnosis of psychogenic non-epileptic seizures. The billing diagnosis codes of 1,730 new, non-selected patient encounters were reviewed over a three-year period for an epileptologist in a neurology clinic to identify all patients with historical diagnoses of fibromyalgia. The frequency with which epileptic seizures, psychogenic non-epileptic seizures, and physiological non-epileptic events were comorbid with fibromyalgia was assessed. Age and gender case-matched controls were used for a between-group comparison. Wilcoxon tests were used to analyse interval data, and Chi-square was used to analyse categorical data (p<0.05). Fibromyalgia was retrospectively identified in 95/1,730 (5.5%) patients in this cohort. Females represented 95% of the fibromyalgia sample (age: 53 years; 95% CI: 57, 51). Forty-three percent of those with fibromyalgia had a non-paroxysmal, neurological primary clinical diagnosis, most commonly chronic pain. Paroxysmal events were present in 57% of fibromyalgia patients and 54% of case-matched controls. Among patients with fibromyalgia and paroxysmal disorders, 11% had epileptic seizures, 74% had psychogenic non-epileptic seizures, and 15% had physiological non-epileptic events, compared to case-matched controls with 37% epileptic seizures, 51% psychogenic non-epileptic events, and 12% physiological non-epileptic events (p = 0.009). Fibromyalgia was shown to be a predictor for the diagnosis of psychogenic non-epileptic seizures in patients with undifferentiated paroxysmal spells. However, our results suggest that the specificity and sensitivity of fibromyalgia as a marker for psychogenic non-epileptic seizures in a mixed general neurological population of patients is less than previously described.

Quest for Accountability: Exploring the Evaluation Process of Universities

ERIC Educational Resources Information Center

Minelli, Eliana; Rebora, Gianfranco; Turri, Matteo

2015-01-01

The article explores the organisational impact of evaluation and control mechanisms on universities from the point of view of accountability. Three case studies are analysed with the aim of understanding the significance of these systems both at corporate governance level and in relation to their influence on the behaviour of the academic staff.…

History Textbook Writing in a Post-Totalitarian and Authoritarian Context: The Case of Belarus

ERIC Educational Resources Information Center

Zadora, Anna

2013-01-01

This paper analyses school history writing in a specific context: Belarus--a post-totalitarian and authoritarian state. School history teaching has always been a powerful instrument for transmitting national identity and legitimising political structures, and political authorities tend to control it. Perestroika marked the beginning of a new…

Genetically Predicted Body Mass Index and Alzheimer’s Disease Related Phenotypes in Three Large Samples: Mendelian Randomization Analyses

PubMed Central

Mukherjee, Shubhabrata; Walter, Stefan; Kauwe, John S.K.; Saykin, Andrew J.; Bennett, David A.; Larson, Eric B.; Crane, Paul K.; Glymour, M. Maria

2015-01-01

Observational research shows that higher body mass index (BMI) increases Alzheimer’s disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian Randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9,613 controls), the Health and Retirement Study (HRS: 8,403 participants with algorithm-predicted dementia status) and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3,177 AD cases and 7,277 controls). No evidence from individual SNPs or polygenic scores indicated BMI increased AD risk. Mendelian Randomization effect estimates per BMI point (95% confidence intervals) were: ADGC OR=0.95 (0.90, 1.01); HRS OR=1.00 (0.75, 1.32); GERAD1 OR=0.96 (0.87, 1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk. PMID:26079416

Pulmonary arterial hypertension associated to systemic erythematous lupus: molecular characterization of 3 cases.

PubMed

Pousada, Guillermo; Lago-Docampo, Mauro; Baloira, Adolfo; Valverde, Diana

2018-03-08

Pulmonary arterial hypertension associated with systemic lupus erythematosus (PAH-SLE) is a rare disease with a low incidence rate. In this study, PAH related genes and genetic modifiers were characterised molecularly in patients with PAH-SLE. Three patients diagnosed with PAH-SLE and 100 control individuals were analysed after signing an informed consent. Two out of the three analysed patients with PAH-SLE were carriers of pathogenic mutations in the genes BMPR2 and ENG. After an in silico analysis, pathogenic mutations were searched for in control individuals and different databases, with negative results, and they were thus functionally analysed. The third patients only showed polymorphisms in the genes BMPR2, ACVRL1 and ENG. Several genetic variants and genetic modifiers were identified in the three analysed patients. These modifiers, along with the pathogenic mutations, could lead to a more severe clinical course in patients with PAH. We present, for the first time, patients with PAH-SLE carrying pathogenic mutations in the main genes related to PAH and alterations in the genetic modifiers. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Responsibility without legal authority? Tackling alcohol-related health harms through licensing and planning policy in local government.

PubMed

Martineau, F P; Graff, H; Mitchell, C; Lock, K

2014-09-01

The power to influence many social determinants of health lies within local government sectors that are outside public health's traditional remit. We analyse the challenges of achieving health gains through local government alcohol control policies, where legal and professional practice frameworks appear to conflict with public health action. Current legislation governing local alcohol control in England and Wales is reviewed and analysed for barriers and opportunities to implement effective population-level health interventions. Case studies of local government alcohol control practices are described. Addressing alcohol-related health harms is constrained by the absence of a specific legal health licensing objective and differences between public health and legal assessments of the relevance of health evidence to a specific place. Local governments can, however, implement health-relevant policies by developing local evidence for alcohol-related health harms; addressing cumulative impact in licensing policy statements and through other non-legislative approaches such as health and non-health sector partnerships. Innovative local initiatives-for example, minimum unit pricing licensing conditions-can serve as test cases for wider national implementation. By combining the powers available to the many local government sectors involved in alcohol control, alcohol-related health and social harms can be tackled through existing local mechanisms. © The Author 2013. Published by Oxford University Press on behalf of Faculty of Public Health.

A review of published analyses of case-cohort studies and recommendations for future reporting.

PubMed

Sharp, Stephen J; Poulaliou, Manon; Thompson, Simon G; White, Ian R; Wood, Angela M

2014-01-01

The case-cohort study design combines the advantages of a cohort study with the efficiency of a nested case-control study. However, unlike more standard observational study designs, there are currently no guidelines for reporting results from case-cohort studies. Our aim was to review recent practice in reporting these studies, and develop recommendations for the future. By searching papers published in 24 major medical and epidemiological journals between January 2010 and March 2013 using PubMed, Scopus and Web of Knowledge, we identified 32 papers reporting case-cohort studies. The median subcohort sampling fraction was 4.1% (interquartile range 3.7% to 9.1%). The papers varied in their approaches to describing the numbers of individuals in the original cohort and the subcohort, presenting descriptive data, and in the level of detail provided about the statistical methods used, so it was not always possible to be sure that appropriate analyses had been conducted. Based on the findings of our review, we make recommendations about reporting of the study design, subcohort definition, numbers of participants, descriptive information and statistical methods, which could be used alongside existing STROBE guidelines for reporting observational studies.

[Correlation between the genetic polymorphisms of apolipoprotein M with the susceptibility to rheumatic diseases of Chinese Han populastion in Lanzhou].

PubMed

Li, Meiyong; Guo, Xinling; Li, Qiannan; You, Chongge

2016-08-01

Objective To investigate the relationship between the genetic polymorphisms of apolipoprotein M (ApoM) and the susceptibility to rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) among Chinese Han population in Lanzhou. Methods Primers for the two single nucleotide polymorphism (SNP) sites (rs805296 and rs805297) in ApoM gene were designed and their genotyping methods of polymerase chain reaction-high resolution melting (PCR-HRM) assay were established. Case-control studies were performed among the 599 cases of RA, 194 cases of SLE, 179 cases of AS and 273 matched healthy controls to analyze the correlations between the two SNPs and the susceptibility to rheumatic diseases. Results The genotype frequencies of rs805296 were AA 87.0%, AG 12.7%, GG 0.3% in RA cases, AA 84.5%, AG 15.0%, GG 0.5% in SLE cases, AA 91.6%, AG 7.3%, GG 1.1% in AS cases, AA 85.0%, AG 15.0%, GG 0% in healthy controls. The ones of rs805297 were GG 38.2%, GT 51.8%, TT 10.0% in RA cases, GG 44.3%, GT 45.4%, TT 10.3% in SLE cases, GG 37.4%, GT 47.5%, TT 15.1% in AS cases, GG 40.7%, GT 46.1%, TT 13.2% in healthy controls. Statistical analyses showed that only the genotype distribution of rs805296 was significantly different between the AS cases and the healthy controls. Under the dominant model, the G allele carriers of rs805296 (AG heterozygote and GG homozygote) were found to significantly decrease the risk for AS development. Conclusion The established PCR-HRM genotyping assays in the present study can successfully achieve the molecular diagnosis of the two SNPs sites (rs805296 and rs805297) from clinical samples, and the study found a significant association between the SNP of rs805296 and the susceptibility to AS among Chinese Han population in Lanzhou.

Does Male Circumcision Protect against Sexually Transmitted Infections? Arguments and Meta-Analyses to the Contrary Fail to Withstand Scrutiny.

PubMed

Morris, Brian J; Hankins, Catherine A; Tobian, Aaron A R; Krieger, John N; Klausner, Jeffrey D

2014-01-01

We critically evaluate a recent article by Van Howe involving 12 meta-analyses that concludes, contrary to current evidence, that male circumcision increases the risk of various common sexually transmitted infections (STIs). Our detailed scrutiny reveals that these meta-analyses (1) failed to include results of all relevant studies, especially data from randomized controlled trials, (2) introduced bias through use of inappropriate control groups, (3) altered original data, in the case of human papillomavirus (HPV), by questionable adjustments for "sampling bias," (4) failed to control for confounders through use of crude odds ratios, and (5) used unnecessarily complicated methods without adequate explanation, so impeding replication by others. Interventions that can reduce the prevalence of STIs are important to international health. Of major concern is the global epidemic of oncogenic types of HPV that contribute to the burden of genital cancers. Meta-analyses, when well conducted, can better inform public health policy and medical practice, but when seriously flawed can have detrimental consequences. Our critical evaluation leads us to reject the findings and conclusions of Van Howe on multiple grounds. Our timely analysis thus reaffirms the medical evidence supporting male circumcision as a desirable intervention for STI prevention.

Does Male Circumcision Protect against Sexually Transmitted Infections? Arguments and Meta-Analyses to the Contrary Fail to Withstand Scrutiny

PubMed Central

Morris, Brian J.; Hankins, Catherine A.; Tobian, Aaron A. R.; Krieger, John N.; Klausner, Jeffrey D.

2014-01-01

We critically evaluate a recent article by Van Howe involving 12 meta-analyses that concludes, contrary to current evidence, that male circumcision increases the risk of various common sexually transmitted infections (STIs). Our detailed scrutiny reveals that these meta-analyses (1) failed to include results of all relevant studies, especially data from randomized controlled trials, (2) introduced bias through use of inappropriate control groups, (3) altered original data, in the case of human papillomavirus (HPV), by questionable adjustments for “sampling bias,” (4) failed to control for confounders through use of crude odds ratios, and (5) used unnecessarily complicated methods without adequate explanation, so impeding replication by others. Interventions that can reduce the prevalence of STIs are important to international health. Of major concern is the global epidemic of oncogenic types of HPV that contribute to the burden of genital cancers. Meta-analyses, when well conducted, can better inform public health policy and medical practice, but when seriously flawed can have detrimental consequences. Our critical evaluation leads us to reject the findings and conclusions of Van Howe on multiple grounds. Our timely analysis thus reaffirms the medical evidence supporting male circumcision as a desirable intervention for STI prevention. PMID:24944836

A New Approach for Identifying Patients with Undiagnosed Chronic Obstructive Pulmonary Disease

PubMed Central

Mannino, David; Leidy, Nancy Kline; Malley, Karen G.; Bacci, Elizabeth D.; Barr, R. Graham; Bowler, Russ P.; Han, MeiLan K.; Houfek, Julia F.; Make, Barry; Meldrum, Catherine A.; Rennard, Stephen; Thomashow, Byron; Walsh, John; Yawn, Barbara P.

2017-01-01

Rationale: Chronic obstructive pulmonary disease (COPD) is often unrecognized and untreated. Objectives: To develop a method for identifying undiagnosed COPD requiring treatment with currently available therapies (FEV1 <60% predicted and/or exacerbation risk). Methods: We conducted a multisite, cross-sectional, case-control study in U.S. pulmonary and primary care clinics that recruited subjects from primary care settings. Cases were patients with COPD and at least one exacerbation in the past year or FEV1 less than 60% of predicted without exacerbation in the past year. Control subjects were persons with no COPD or with mild COPD (FEV1 ≥60% predicted, no exacerbation in the past year). In random forests analyses, we identified the smallest set of questions plus peak expiratory flow (PEF) with optimal sensitivity (SN) and specificity (SP). Measurements and Main Results: PEF and spirometry were recorded in 186 cases and 160 control subjects. The mean (SD) age of the sample population was 62.7 (10.1) years; 55% were female; 86% were white; and 16% had never smoked. The mean FEV1 percent predicted for cases was 42.5% (14.2%); for control subjects, it was 82.5% (15.7%). A five-item questionnaire, CAPTURE (COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk), was used to assess exposure, breathing problems, tiring easily, and acute respiratory illnesses. CAPTURE exhibited an SN of 95.7% and an SP of 44.4% for differentiating cases from all control subjects, and an SN of 95.7% and an SP of 67.8% for differentiating cases from no-COPD control subjects. The PEF (males, <350 L/min; females, <250 L/min) SN and SP were 88.0% and 77.5%, respectively, for differentiating cases from all control subjects, and they were 88.0% and 90.8%, respectively, for distinguishing cases from no-COPD control subjects. The CAPTURE plus PEF exhibited improved SN and SP for all cases versus all control subjects (89.7% and 78.1%, respectively) and for all cases versus no-COPD control subjects (89.7% and 93.1%, respectively). Conclusions: CAPTURE with PEF can identify patients with COPD who would benefit from currently available therapy and require further diagnostic evaluation. Clinical trial registered with clinicaltrials.gov (NCT01880177). PMID:27783539

Cost-effectiveness of adding indoor residual spraying to case management in Afghan refugee settlements in Northwest Pakistan during a prolonged malaria epidemic

PubMed Central

Guinness, Lorna; Rowland, Mark; Durrani, Naeem; Hansen, Kristian S.

2017-01-01

Introduction Financing of malaria control for displaced populations is limited in scope and duration, making cost-effectiveness analyses relevant but difficult. This study analyses cost-effectiveness of adding prevention through targeted indoor residual spraying (IRS) to case management in Afghan refugee settlements in Pakistan during a prolonged malaria epidemic. Methods/Findings An intervention study design was selected, taking a societal perspective. Provider and household costs of vector control and case management were collected from provider records and community survey. Health outcomes (e.g. cases and DALYs averted) were derived and incremental cost-effectiveness ratios (ICERs) for cases prevented and DALYs averted calculated. Population, treatment cost, women’s time, days of productivity lost, case fatality rate, cases prevented, and DALY assumptions were tested in sensitivity analysis. Malaria incidence peaked at 44/1,000 population in year 2, declining to 14/1,000 in year 5. In total, 370,000 malaria cases, 80% vivax, were diagnosed and treated and an estimated 67,988 vivax cases and 18,578 falciparum and mixed cases prevented. Mean annual programme cost per capita was US$0.56. The additional cost of including IRS over five years per case prevented was US$39; US$50 for vivax (US$43 in years 1–3, US$80 in years 4–5) and US$182 for falciparum (US$139 in years 1–3 and US$680 in years 4–5). Per DALY averted this was US$266 (US$220 in years 1–3 and US$486 in years 4–5) and thus ‘highly cost-effective’ or cost-effective using WHO and comparison thresholds. Conclusions Adding IRS was cost-effective in this moderate endemicity, low mortality setting. It was more cost-effective when transmission was highest, becoming less so as transmission reduced. Because vivax was three times more common than falciparum and the case fatality rate was low, cost-effectiveness estimations for cases prevented appear reliable and more definitive for vivax malaria. PMID:29059179

A mega-analysis of genome-wide association studies for major depressive disorder.

PubMed

Ripke, Stephan; Wray, Naomi R; Lewis, Cathryn M; Hamilton, Steven P; Weissman, Myrna M; Breen, Gerome; Byrne, Enda M; Blackwood, Douglas H R; Boomsma, Dorret I; Cichon, Sven; Heath, Andrew C; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A F; Martin, Nicholas G; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M; Penninx, Brenda P; Pergadia, Michele L; Potash, James B; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H; Preisig, Martin; Smoller, Jordan W; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R; Bettecken, Thomas; Binder, Elisabeth B; Breuer, René; Castro, Victor M; Churchill, Susanne E; Coryell, William H; Craddock, Nick; Craig, Ian W; Czamara, Darina; De Geus, Eco J; Degenhardt, Franziska; Farmer, Anne E; Fava, Maurizio; Frank, Josef; Gainer, Vivian S; Gallagher, Patience J; Gordon, Scott D; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K; Herms, Stefan; Hickie, Ian B; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A; Kohane, Isaac S; Kohli, Martin A; Korszun, Ania; Landen, Mikael; Lawson, William B; Lewis, Glyn; Macintyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M; Middleton, Lefkos; Montgomery, Grant M; Murphy, Shawn N; Nauck, Matthias; Nolen, Willem A; Nyholt, Dale R; O'Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A; Schulz, Andrea; Schulze, Thomas G; Shyn, Stanley I; Sigurdsson, Engilbert; Slager, Susan L; Smit, Johannes H; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J C G; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B; Willemsen, Gonneke; Zitman, Frans G; Neale, Benjamin; Daly, Mark; Levinson, Douglas F; Sullivan, Patrick F

2013-04-01

Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 × 10(-9) at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.

Assessing interactions between the associations of common genetic susceptibility variants, reproductive history and body mass index with breast cancer risk in the breast cancer association consortium: a combined case-control study

PubMed Central

2010-01-01

Introduction Several common breast cancer genetic susceptibility variants have recently been identified. We aimed to determine how these variants combine with a subset of other known risk factors to influence breast cancer risk in white women of European ancestry using case-control studies participating in the Breast Cancer Association Consortium. Methods We evaluated two-way interactions between each of age at menarche, ever having had a live birth, number of live births, age at first birth and body mass index (BMI) and each of 12 single nucleotide polymorphisms (SNPs) (10q26-rs2981582 (FGFR2), 8q24-rs13281615, 11p15-rs3817198 (LSP1), 5q11-rs889312 (MAP3K1), 16q12-rs3803662 (TOX3), 2q35-rs13387042, 5p12-rs10941679 (MRPS30), 17q23-rs6504950 (COX11), 3p24-rs4973768 (SLC4A7), CASP8-rs17468277, TGFB1-rs1982073 and ESR1-rs3020314). Interactions were tested for by fitting logistic regression models including per-allele and linear trend main effects for SNPs and risk factors, respectively, and single-parameter interaction terms for linear departure from independent multiplicative effects. Results These analyses were applied to data for up to 26,349 invasive breast cancer cases and up to 32,208 controls from 21 case-control studies. No statistical evidence of interaction was observed beyond that expected by chance. Analyses were repeated using data from 11 population-based studies, and results were very similar. Conclusions The relative risks for breast cancer associated with the common susceptibility variants identified to date do not appear to vary across women with different reproductive histories or body mass index (BMI). The assumption of multiplicative combined effects for these established genetic and other risk factors in risk prediction models appears justified. PMID:21194473

When is category specific in Alzheimer's disease?

PubMed

Laws, Keith R; Gale, Tim M; Leeson, Verity C; Crawford, John R

2005-08-01

Mixed findings have emerged concerning whether category-specific disorders occur in Alzheimer's disease. Factors that may contribute to these inconsistencies include: ceiling effects/skewed distributions for control data in some studies; differences in the severity of cognitive deficit in patients; and differences in the type of analysis (in particular, if and how controls are used to analyse single case data). We examined picture naming in Alzheimer's patients and matched elderly healthy normal controls in three experiments. These experiments used stimuli that did and did not produce ceiling effects/skewed data in controls. In Experiment 1, we examined for category effects in individual DAT patients using commonly used analyses for single cases (chi2 and z-scores). The different techniques produced quite different outcomes. In Experiment 2a, we used the same techniques on a different group of patients with similar outcomes. Finally, in Experiment 2b, we examined the same patients but (a) used stimuli that did not produce ceiling effects/skewed distributions in healthy controls, and (b) used statistical methods that did not treat the control sample as a population. We found that ceiling effects in controls may markedly inflate the incidence of dissociations in which living things are differentially impaired and seriously underestimate dissociations in the opposite direction. In addition, methods that treat the control sample as a population led to inflation in the overall number of dissociations detected. These findings have implications for the reliability of category effects previously reported both in Alzheimer patients and in other pathologies. In particular, they suggest that the greater proportion of living than nonliving deficits reported in the literature may be an artifact of the methods used.

Selected vitamin D metabolic gene variants and risk for autism spectrum disorder in the CHARGE Study.

PubMed

Schmidt, Rebecca J; Hansen, Robin L; Hartiala, Jaana; Allayee, Hooman; Sconberg, Jaime L; Schmidt, Linda C; Volk, Heather E; Tassone, Flora

2015-08-01

Vitamin D is essential for proper neurodevelopment and cognitive and behavioral function. We examined associations between autism spectrum disorder (ASD) and common, functional polymorphisms in vitamin D pathways. Children aged 24-60 months enrolled from 2003 to 2009 in the population-based CHARGE case-control study were evaluated clinically and confirmed to have ASD (n=474) or typical development (TD, n=281). Maternal, paternal, and child DNA samples for 384 (81%) families of children with ASD and 234 (83%) families of TD children were genotyped for: TaqI, BsmI, FokI, and Cdx2 in the vitamin D receptor (VDR) gene, and CYP27B1 rs4646536, GC rs4588, and CYP2R1 rs10741657. Case-control logistic regression, family-based log-linear, and hybrid log-linear analyses were conducted to produce risk estimates and 95% confidence intervals (CI) for each allelic variant. Paternal VDR TaqI homozygous variant genotype was significantly associated with ASD in case-control analysis (odds ratio [OR] [CI]: 6.3 [1.9-20.7]) and there was a trend towards increased risk associated with VDR BsmI (OR [CI]: 4.7 [1.6-13.4]). Log-linear triad analyses detected parental imprinting, with greater effects of paternally-derived VDR alleles. Child GC AA-genotype/A-allele was associated with ASD in log-linear and ETDT analyses. A significant association between decreased ASD risk and child CYP2R1 AA-genotype was found in hybrid log-linear analysis. There were limitations of low statistical power for less common alleles due to missing paternal genotypes. This study provides preliminary evidence that paternal and child vitamin D metabolism could play a role in the etiology of ASD; further research in larger study populations is warranted. Copyright © 2015. Published by Elsevier Ireland Ltd.

Lipoprotein (a) as a risk factor for ischemic stroke: a meta-analysis.

PubMed

Nave, Alexander H; Lange, Kristin S; Leonards, Christopher O; Siegerink, Bob; Doehner, Wolfram; Landmesser, Ulf; Steinhagen-Thiessen, Elisabeth; Endres, Matthias; Ebinger, Martin

2015-10-01

Lipoprotein (a) [Lp(a)] harbors atherogenic potential but its role as a risk factor for ischemic stroke remains controversial. We conducted a meta-analysis to determine the relative strength of the association between Lp(a) and ischemic stroke and identify potential subgroup-specific risk differences. A systematic search using the MeSH terms "lipoproteins" OR "lipoprotein a" AND "stroke" was performed in PubMed and ScienceDirect for case-control studies from June 2006 and prospective cohort studies from April 2009 until December 20th 2014. Data from eligible papers published before these dates were reviewed and extracted from previous meta-analyses. Studies that assessed the relationship between Lp(a) levels and ischemic stroke and reported generic data-i.e. odds ratio [OR], hazard ratio, or risk ratio [RR]-were eligible for inclusion. Studies that not distinguish between ischemic and hemorrhagic stroke and transient ischemic attack were excluded. Random effects meta-analyses with mixed-effects meta-regression were performed by pooling adjusted OR or RR. A total of 20 articles comprising 90,904 subjects and 5029 stroke events were eligible for the meta-analysis. Comparing high with low Lp(a) levels, the pooled estimated OR was 1.41 (95% CI, 1.26-1.57) for case-control studies (n = 11) and the pooled estimated RR was 1.29 (95% CI, 1.06-1.58) for prospective studies (n = 9). Sex-specific differences in RR were inconsistent between case-control and prospective studies. Study populations with a mean age of ≤55 years had an increased RR compared to older study populations. Reported Lp(a) contrast levels and ischemic stroke subtype significantly contributed to the heterogeneity observed in the analyses. Elevated Lp(a) is an independent risk factor for ischemic stroke and may be especially relevant for young stroke patients. Sex-specific risk differences remain conflicting. Further studies in these subgroups may be warranted. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluation of Maternal and Perinatal Outcomes of Induction in Borderline Oligohydramnios at Term.

PubMed

Rathod, Setu; Samal, Sunil Kumar

2017-09-01

Oligohydramnios is described as decreased amniotic fluid volume relative to gestational age. Semiquantitatively it is described using the Amniotic Fluid Index (AFI) which is calculated by adding the depth in centimetres of the largest vertical pocket in each of four equal uterine quadrants. AFI less than or equal to 5 cm is defined as oligohydramnios. A Borderline Oligohydramnios (BO) is defined as AFI 5.1-8 cm. To assess the maternal and perinatal outcome of induction in borderline oligohydramnios cases at term. This is a retrospective observational study done from December 2015 to November 2016 in Mahatma Gandhi Medical College and Research Institute, Puducherry, India. Fifty cases of BO with AFI 5.1 cm - 8 cm taken as case and another 50 cases of Normal Liquor (NL) with AFI 8.1 cm - 18 cm taken as control. Data was collected and analysed by SPSS software version 20.0 For qualitative data, the χ 2 -test or Fisher's-exact test were used and for continuous variables, the t-test was used. Cases and controls were matched in baseline parameters. More number of cases were found with meconium stained liquor during labour which is statistically significant (p<0.05). Otherwise there were no statistical significant difference between cases and controls in maternal and perinatal outcome. Induction of labour in cases with BO cases compared to those with NL at term did not show very statistically significant difference in terms of induction to delivery interval and neonatal outcome.

Working conditions of bus drivers in the private sector and bus crashes in Kandy district, Sri Lanka: a case-control study.

PubMed

Jayatilleke, A U; Nakahara, S; Dharmaratne, S D; Jayatilleke, A C; Poudel, K C; Jimba, M

2009-04-01

To explore the effects of working conditions of private-bus drivers on bus crashes in Kandy district, Sri Lanka. A case-control study was carried out from August to September 2006. All private-bus drivers registered in Kandy district and involved in crashes reported to the police between November 2005 and April 2006 (n = 63) were selected as cases. Two control groups were included: private-bus drivers working on the same routes as the case drivers (n = 90) and private-bus drivers selected randomly from other routes of the district (n = 111). Data were collected using an anonymous self-administered questionnaire. Associations between working conditions and crashes were analysed using logistic regression. A strong association was observed between drivers' disagreements about working hours and bus crashes (matched controls, adjusted odds ratio (AOR) 5.98, 95% CI 1.02 to 34.90; unmatched controls, AOR 18.74, 95% CI 2.00 to 175.84). A significant association was also observed between low salaries (

A Case Control Study Reveals that Polyomaviruria Is Significantly Associated with Interstitial Cystitis and Vesical Ulceration

PubMed Central

Winter, Benjamin J.; O'Connell, Helen E.; Bowden, Scott; Carey, Marcus; Eisen, Damon P.

2015-01-01

Objectives To investigate whether polyomaviruses contribute to interstitial cystitis pathogenesis. Subjects and Methods A prospective study was performed with 50 interstitial cystitis cases compared with 50 age-matched, disease-free controls for the frequency of polyomaviruria. Associations between polyomaviruria and disease characteristics were analysed in cases. Polyomavirus in urine and bladder tissue was detected with species (JC virus vs. BK virus) specific, real-time PCR. Results Case patients were reflective of interstitial cystitis epidemiology with age range from 26–88 years (median 58) and female predominance (41/50 F). There was a significant increase in the frequency of polyomavirus shedding between cases and controls (p<0.02). Polyomavirus shedding, in particular BK viruria, was associated with vesical ulceration, a marker of disease severity, among interstitial cystitis cases after adjustment for age and sex (OR 6.8, 95% CI 1.89–24.4). There was a significant association among cases between the presence of BK viruria and response to intravesical Clorpactin therapy (OR 4.50, 95% CI 1.17–17.4). Conclusion The presence of polyomaviruria was found to be associated with the ulcerative form of interstitial cystitis. Clorpactin, which has anti-DNA virus activity, was more likely to improve symptoms in the presence of BK viruria. These data from this pilot study suggest associations between polyomaviruria and interstitial cystitis warranting further investigation. PMID:26325074

A Multicenter Study of Glucocerebrosidase Mutations in Dementia With Lewy Bodies

PubMed Central

Nalls, Michael A.; Duran, Raquel; Lopez, Grisel; Kurzawa-Akanbi, Marzena; McKeith, Ian G.; Chinnery, Patrick F.; Morris, Christopher M.; Theuns, Jessie; Crosiers, David; Cras, Patrick; Engelborghs, Sebastiaan; De Deyn, Peter Paul; Van Broeckhoven, Christine; Mann, David M. A.; Snowden, Julie; Pickering-Brown, Stuart; Halliwell, Nicola; Davidson, Yvonne; Gibbons, Linda; Harris, Jenny; Sheerin, Una-Marie; Bras, Jose; Hardy, John; Clark, Lorraine; Marder, Karen; Honig, Lawrence S.; Berg, Daniela; Maetzler, Walter; Brockmann, Kathrin; Gasser, Thomas; Novellino, Fabiana; Quattrone, Aldo; Annesi, Grazia; De Marco, Elvira Valeria; Rogaeva, Ekaterina; Masellis, Mario; Black, Sandra E.; Bilbao, Juan M.; Foroud, Tatiana; Ghetti, Bernardino; Nichols, William C.; Pankratz, Nathan; Halliday, Glenda; Lesage, Suzanne; Klebe, Stephan; Durr, Alexandra; Duyckaerts, Charles; Brice, Alexis; Giasson, Benoit I.; Trojanowski, John Q.; Hurtig, Howard I.; Tayebi, Nahid; Landazabal, Claudia; Knight, Melanie A.; Keller, Margaux; Singleton, Andrew B.; Wolfsberg, Tyra G.; Sidransky, Ellen

2013-01-01

Importance While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders. Objective To establish whether GBA1 mutations are a risk factor for dementia with Lewy bodies (DLB). Design We compared genotype data on patients and controls from 11 centers. Data concerning demographics, age at onset, disease duration, and clinical and pathological features were collected when available. We conducted pooled analyses using logistic regression to investigate GBA1 mutation carrier status as predicting DLB or PD with dementia status, using common control subjects as a reference group. Random-effects meta-analyses were conducted to account for additional heterogeneity. Setting Eleven centers from sites around the world performing genotyping. Participants Seven hundred twenty-one cases met diagnostic criteria for DLB and 151 had PD with dementia. We compared these cases with 1962 controls from the same centers matched for age, sex, and ethnicity. Main Outcome Measures Frequency of GBA1 mutations in cases and controls. Results We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78–14.88). The odds ratio for PD with dementia was 6.48 (95% CI, 2.53–15.37). The mean age at diagnosis of DLB was earlier in GBA1 mutation carriers than in noncarriers (63.5 vs 68.9 years; P<.001), with higher disease severity scores. Conclusions and Relevance Mutations in GBA1 are a significant risk factor for DLB. GBA1 mutations likely play an even larger role in the genetic etiology of DLB than in PD, providing insight into the role of glucocerebrosidase in Lewy body disease. PMID:23588557

Genetic variations and risk of placental abruption: A genome-wide association study and meta-analysis of genome-wide association studies.

PubMed

Workalemahu, Tsegaselassie; Enquobahrie, Daniel A; Gelaye, Bizu; Sanchez, Sixto E; Garcia, Pedro J; Tekola-Ayele, Fasil; Hajat, Anjum; Thornton, Timothy A; Ananth, Cande V; Williams, Michelle A

2018-06-01

Accumulating epidemiological evidence points to strong genetic susceptibility to placental abruption (PA). However, characterization of genes associated with PA remains incomplete. We conducted a genome-wide association study (GWAS) of PA and a meta-analysis of GWAS. Participants of the Placental Abruption Genetic Epidemiology (PAGE) study, a population based case-control study of PA conducted in Lima, Peru, were genotyped using the Illumina HumanCore-24 BeadChip platform. Genotypes were imputed using the 1000 genomes reference panel, and >4.9 million SNPs that passed quality control were analyzed. We performed a GWAS in PAGE participants (507 PA cases and 1090 controls) and a GWAS meta-analysis in 2512 participants (959 PA cases and 1553 controls) that included PAGE and the previously reported Peruvian Abruptio Placentae Epidemiology (PAPE) study. We fitted population stratification-adjusted logistic regression models and fixed-effects meta-analyses using inverse-variance weighting. Independent loci (linkage-disequilibrium<0.80) suggestively associated with PA (P-value<5e-5) included rs4148646 and rs2074311 in ABCC8, rs7249210, rs7250184, rs7249100 and rs10401828 in ZNF28, rs11133659 in CTNND2, and rs2074314 and rs35271178 near KCNJ11 in the PAGE GWAS. Similarly, independent loci suggestively associated with PA in the GWAS meta-analysis included rs76258369 near IRX1, and rs7094759 and rs12264492 in ADAM12. Functional analyses of these genes showed trophoblast-like cell interaction, as well as networks involved in endocrine system disorders, cardiovascular diseases, and cellular function. We identified several genetic loci and related functions that may play a role in PA risk. Understanding genetic factors underlying pathophysiological mechanisms of PA may facilitate prevention and early diagnostic efforts. Published by Elsevier Ltd.

Inherited thrombophilia and pregnancy loss. Study of an Argentinian cohort.

PubMed

Perés Wingeyer, Silvia; Aranda, Federico; Udry, Sebastián; Latino, José; de Larrañaga, Gabriela

2018-03-06

Thrombophilia might increase the risk of suffering from obstetric complications by adversely affecting the normal placental vascular function. Our aim was to study the distributions of five thrombosis-associated genetic variants: factor V Leiden, prothrombin G20210A, -675 4G/5G PAI-1, 10034C/T gamma fibrinogen and 7872C/T factor XI and the frequencies of the deficiencies of protein C, S and antithrombin in Argentinian patients with recurrent pregnancy loss (RPL) and, therefore, to analyse their association with the risk and timing of RPL and the risk of suffering other vascular obstetric pathologies. We performed a case-control study that included 247 patients with idiopathic RPL (cases), 107 fertile controls and 224 subjects from general population (reference group). Cases were stratified according to the gestational time of the losses (early RPL, n = 89; late losses, n = 158; foetal losses, n = 107) and according to the type of vascular obstetric pathologies. No differences were found in the distribution of the genetic variants among RPL group vs. control/reference group (p >.05). Similarly, no differences were observed in their distributions when analysing RPL patients stratified according to gestational times or vascular obstetric pathologies (p >.05), except for the factor V Leiden carriage in patients with foetal growth retardation vs. controls (11.8%, 4/34 vs. 1.9%, 2/107; p = .04) (OR = 7.11 [1.24-40.93], p = .03). Factor V Leiden might have a significant impact on certain obstetric pathologies such as foetal growth retardation. The genetic variants, 10034C/T gamma fibrinogen and 7872C/T factor XI, associated with thromboembolic disease, would not have an impact on PRE. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Lung cancer and socioeconomic status in a pooled analysis of case-control studies

PubMed Central

Hovanec, Jan; Siemiatycki, Jack; Conway, David I.; Olsson, Ann; Stücker, Isabelle; Guida, Florence; Jöckel, Karl-Heinz; Pohlabeln, Hermann; Ahrens, Wolfgang; Brüske, Irene; Wichmann, Heinz-Erich; Gustavsson, Per; Consonni, Dario; Merletti, Franco; Richiardi, Lorenzo; Simonato, Lorenzo; Fortes, Cristina; Parent, Marie-Elise; McLaughlin, John; Demers, Paul; Landi, Maria Teresa; Caporaso, Neil; Tardón, Adonina; Zaridze, David; Szeszenia-Dabrowska, Neonila; Rudnai, Peter; Lissowska, Jolanta; Fabianova, Eleonora; Field, John; Dumitru, Rodica Stanescu; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Kromhout, Hans; Vermeulen, Roel; Boffetta, Paolo; Straif, Kurt; Schüz, Joachim; Kendzia, Benjamin; Pesch, Beate; Brüning, Thomas; Behrens, Thomas

2018-01-01

Background An association between low socioeconomic status (SES) and lung cancer has been observed in several studies, but often without adequate control for smoking behavior. We studied the association between lung cancer and occupationally derived SES, using data from the international pooled SYNERGY study. Methods Twelve case-control studies from Europe and Canada were included in the analysis. Based on occupational histories of study participants we measured SES using the International Socio-Economic Index of Occupational Status (ISEI) and the European Socio-economic Classification (ESeC). We divided the ISEI range into categories, using various criteria. Stratifying by gender, we calculated odds ratios (OR) and 95% confidence intervals (CI) by unconditional logistic regression, adjusting for age, study, and smoking behavior. We conducted analyses by histological subtypes of lung cancer and subgroup analyses by study region, birth cohort, education and occupational exposure to known lung carcinogens. Results The analysis dataset included 17,021 cases and 20,885 controls. There was a strong elevated OR between lung cancer and low SES, which was attenuated substantially after adjustment for smoking, however a social gradient persisted. SES differences in lung cancer risk were higher among men (lowest vs. highest SES category: ISEI OR 1.84 (95% CI 1.61–2.09); ESeC OR 1.53 (95% CI 1.44–1.63)), than among women (lowest vs. highest SES category: ISEI OR 1.54 (95% CI 1.20–1.98); ESeC OR 1.34 (95% CI 1.19–1.52)). Conclusion SES remained a risk factor for lung cancer after adjustment for smoking behavior. PMID:29462211

Association between non-steroidal anti-inflammatory drug use and melanoma risk: a meta-analysis of 13 studies.

PubMed

Li, Shan; Liu, Yanqiong; Zeng, Zhiyu; Peng, Qiliu; Li, Ruolin; Xie, Li; Qin, Xue; Zhao, Jinmin

2013-08-01

Results of the association between non-steroidal anti-inflammatory drugs (NSAIDs) and melanoma risk have been inconsistent. We performed a meta-analysis of relevant studies to investigate the hypothesis of an association between NSAID use and melanoma risk. Systematic searches of the PubMed and several other databases up to 23 March 2013 were retrieved. All epidemiologic studies regarding NSAIDs and melanoma risk were included. Fixed- or random-effects meta-analytical models were used to calculate relative risk (RR) and corresponding 95 % confidence intervals (CIs). Sensitivity analyses, Galbraith plots, and subgroup analyses were also performed. Six case-control studies including 93,432 melanoma cases and 401,251 controls, six cohort studies consisting of 563,380 subjects, and one randomized controlled trial encompassing 39,876 participants were included in this analysis. Compared to non-use, ever use of any NSAIDs was not statistically significantly associated with melanoma risk based on the random-effects models (RR = 0.97, 95 % CI = 0.90-10.4, p = 0.401). No differences were found in the effects on melanoma risk of aspirin, non-aspirin NSAIDs, and cyclooxygenase-2 inhibitor use overall and stratified by gender. However, a slight reduction in the risk of melanoma by taking aspirin was observed in case-control studies (RR = 0.88, 95 % CI = 0.80-0.96, p = 0.004). Findings from this pooled analysis do not support the hypothesis that NSAID use provides potential benefits in preventing melanoma. More and larger randomized trials, including adequate numbers of patients, are required to further evaluate the relationship between NSAID use and melanoma.

The association of lifetime physical inactivity with bladder and renal cancer risk: A hospital-based case-control analysis.

PubMed

Cannioto, Rikki; Etter, John Lewis; Guterman, Lauren Beryl; Joseph, Janine M; Gulati, Nicholas R; Schmitt, Kristina L; LaMonte, Michael J; Nagy, Ryan; Minlikeeva, Albina; Szender, James Brian; Moysich, Kirsten B

2017-08-01

Recreational physical inactivity has been gaining recognition as an independent epidemiological exposure of interest in relation to cancer endpoints due to evidence suggesting that it may associate with cancer independent of obesity. In the current analyses, we examined the associations of lifetime recreational physical inactivity with renal and bladder cancer risk. In this hospital-based case-control study, we identified N=160 renal cancer patients, N=208 bladder cancer patients, and N=766 age frequency-matched controls without cancer. Participants self-reporting never participating in any regular/weekly recreational physical activity throughout their lifetime were classified as physically inactive. Utilizing unconditional multivariable logistic regression analyses, we estimated odds ratios and 95% confidence intervals to represent the associations between lifetime physical inactivity and renal and bladder cancer risk. In multivariable logistic regression models, we observed significant positive associations between lifetime recreational physical inactivity and renal cancer and bladder cancer risk: odds ratio=1.77 (95% CI: 1.10-2.85) and odds ratio=1.73 (95% CI: 1.13-2.63), respectively. Similar associations also persisted among individuals who were not obese for both renal and bladder cancer: odds ratio=1.75 (95% CI: 1.03-2.98) and odds ratio=1.70 (95% CI: 1.08-2.69), respectively. In this case-control study, we observed evidence of a positive association between renal and bladder cancer with lifetime recreational physical inactivity. These data add to the growing body of evidence suggesting that physical inactivity may be an important independent risk factor for cancer. However, additional studies using a larger sample and prospectively collected data are needed to substantiate the current findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Factors associated with poor knowledge among adults on tuberculosis in Bangladesh: results from a nationwide survey.

PubMed

Hossain, Shahed; Zaman, Khalequ; Quaiyum, Abdul; Banu, Sayera; Husain, Ashaque; Islam, Akramul; Borgdorff, Martien; van Leth, Frank

2015-05-01

In 2012, Bangladesh continues to be one of the 22 high tuberculosis (TB) burden countries in the world. Although free diagnosis and management for TB is available throughout the country, case notification rate/100,000 population for new smear positive (NSP) cases under the national TB control programme (NTP) remained at around 70/100,000 population and have not changed much since 2006. Knowledge on TB disease, treatment and its management could be an important predictor for utilization of TB services and influence case detection under the NTP. Our objective is to describe knowledge of TB among newly diagnosed TB cases and community controls to assess factors associated with poor knowledge in order to identify programmatic implications for control measures. Embedded in TB prevalence survey 2007-2009, we included 240 TB cases from the TB registers and 240 persons ≥ 15 years of age randomly selected from the households where the survey was implemented. All participants were interviewed using a structured, pre-tested questionnaire to evaluate their TB knowledge. Regression analyses were done to assess associations with poor knowledge of TB. Our survey documented that overall there was fair knowledge in all domains investigated. However, based on the number of correct answers to the questionnaires, community controls showed significantly poorer knowledge than the TB cases in the domains of TB transmission (80% vs. 88%), mode of transmission (67% vs. 82%), knowing ≥ 1 suggestive symptoms including cough (78% vs. 89%), curability of TB (90% vs. 98%) and availability of free treatment (75% vs. 95%). Community controls were more likely to have poor knowledge of TB issues compared to the TB cases even after controlling for other factors such as education and occupation in a multivariate model (OR 3.46, 95% CI: 2.00-6.09). Knowledge on various aspects of TB and TB services varies significantly between TB cases and community controls in Bangladesh. The overall higher levels of knowledge in TB cases could identify them as peer educators in ongoing communication approaches to improve care seeking behavior of the TB suspects in the community and hence case detection.

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.

A recessive genetic model and runs of homozygosity in major depressive disorder

PubMed Central

Power, Robert A.; Keller, Matthew C.; Ripke, Stephan; Abdellaoui, Abdel; Wray, Naomi R.; Sullivan, Patrick F; Breen, Gerome

2014-01-01

Genome-wide association studies (GWASs) of major depressive disorder (MDD) have yet to identify variants that surpass the threshold for genome-wide significance. A recent study reported that runs of homozygosity (ROH) are associated with schizophrenia, reflecting a novel genetic risk factor resulting from increased parental relatedness and recessive genetic effects. Here we undertake an analysis of ROH for MDD using the 9,238 MDD cases and 9,521 controls reported in a recent mega-analysis of 9 GWAS. Since evidence for association with ROH could reflect a recessive mode of action at loci, we also conducted a genome-wide association analyses under a recessive model. The genome-wide association analysis using a recessive model found no significant associations. Our analysis of ROH suggested that there was significant heterogeneity of effect across studies in effect (p=0.001), and it was associated with genotyping platform and country of origin. The results of the ROH analysis show that differences across studies can lead to conflicting systematic genome-wide differences between cases and controls that are unaccounted for by traditional covariates. They highlight the sensitivity of the ROH method to spurious associations, and the need to carefully control for potential confounds in such analyses. We found no strong evidence for a recessive model underlying MDD. PMID:24482242

ACTN3 R577X polymorphism and explosive leg-muscle power in elite basketball players.

PubMed

Garatachea, Nuria; Verde, Zoraida; Santos-Lozano, Alejandro; Yvert, Thomas; Rodriguez-Romo, Gabriel; Sarasa, Francisco J; Hernández-Sánchez, Sonsoles; Santiago, Catalina; Lucia, Alejandro

2014-03-01

To determine the association of the ACTN3 R577X polymorphism with leg-muscle explosive power in Spanish (white) elite basketball players and controls. 100 (60 men) elite basketball players (cases) and 283 nonathletic controls. The authors assessed power performance by means of the vertical-squat and countermovement-jump tests. Genotype distributions did not differ between groups (cases: 37.0% [RR], 42.0% [RX], and 21.0% [XX]; controls: 31.8% [RR], 49.8% [RX], and 18.4% [XX]; P = .353). The authors did not observe any effect of the ACTN3 R577X polymorphism on study phenotypes in either group, including when they performed the analyses separately in men and women. They found no association between the ACTN3 R577X polymorphism and the likelihood of being an elite basketball player using the dominant or the recessive model, and the results remained unaltered when the analyses were adjusted for sex, weight, height, and age or when performed for men and women separately. Although the ACTN3 R577X is associated with explosive muscle performance and this phenotype is important in the sport of basketball (ie, during jumps), the authors found no association with leg explosive power in elite basket players or with the status of being this type of athlete.

Disturbed eating behavior and eating disorders in preteen and early teenage girls with type 1 diabetes: a case-controlled study.

PubMed

Colton, Patricia; Olmsted, Marion; Daneman, Denis; Rydall, Anne; Rodin, Gary

2004-07-01

To compare the prevalence of eating disturbances in preteen and early teenage girls with type 1 diabetes to their nondiabetic peers. A cross-sectional, case-controlled study of 101 girls with type 1 diabetes, ages 9-14 years, and 303 age-matched, female nondiabetic control subjects was conducted. Participants completed a Children's Eating Disorder Examination interview. Socioeconomic status, BMI, and diabetes-related variables were assessed. Groups were compared using chi(2) analyses. Binge eating; the use of intense, excessive exercise for weight control; the combination of two disturbed eating-related behaviors; and subthreshold eating disorders were all more common in girls with type 1 diabetes. Metabolic control was not related to eating behavior in this study population. Eating disturbances, though mostly mild, were significantly more common in preteen and early teenage girls with type 1 diabetes. Screening and prevention programs for this high-risk group should begin in the preteen years.

Impact of Time to Maternal Interview on Interview Responses in the National Birth Defects Prevention Study

PubMed Central

Tinker, Sarah C.; Gibbs, Cassandra; Strickland, Matthew J.; Devine, Owen J.; Crider, Krista S.; Werler, Martha M.; Anderka, Marlene T.; Reefhuis, Jennita

2013-01-01

Prenatal exposures often are assessed using retrospective interviews. Time from exposure to interview may influence data accuracy. We investigated the association of time to interview (TTI) with aspects of interview responses in the National Birth Defects Prevention Study, a population-based case-control study of birth defects in 10 US states. Mothers completed a computer-assisted telephone interview 1.5–24 months after their estimated date of delivery. Proxy metrics for interview quality were whether certain exposures were reported, whether the start month of reported medication use or illness was reported, or whether responses were missing. Interaction by case status was assessed. Interviews were completed with 30,542 mothers (22,366 cases and 8,176 controls) who gave birth between 1997 and 2007. Mothers of cases were interviewed later than were mothers of controls (11.7 months vs. 9.5 months, respectively). In adjusted analyses, having a TTI that was greater than 6 months was associated with only a few aspects of interview responses (e.g., start month of pseudoephedrine use). Interaction by case-control status was observed for some exposures; mothers of controls had a greater reduction in interview quality with increased TTI in these instances (e.g., report of morning sickness, start month of acetaminophen use and ibuprofen use). The results suggest that TTI might impact interview responses; however, the impact may be minimal and specific to the type of exposure. PMID:23645625

Impact of time to maternal interview on interview responses in the National Birth Defects Prevention Study.

PubMed

Tinker, Sarah C; Gibbs, Cassandra; Strickland, Matthew J; Devine, Owen J; Crider, Krista S; Werler, Martha M; Anderka, Marlene T; Reefhuis, Jennita

2013-06-01

Prenatal exposures often are assessed using retrospective interviews. Time from exposure to interview may influence data accuracy. We investigated the association of time to interview (TTI) with aspects of interview responses in the National Birth Defects Prevention Study, a population-based case-control study of birth defects in 10 US states. Mothers completed a computer-assisted telephone interview 1.5-24 months after their estimated date of delivery. Proxy metrics for interview quality were whether certain exposures were reported, whether the start month of reported medication use or illness was reported, or whether responses were missing. Interaction by case status was assessed. Interviews were completed with 30,542 mothers (22,366 cases and 8,176 controls) who gave birth between 1997 and 2007. Mothers of cases were interviewed later than were mothers of controls (11.7 months vs. 9.5 months, respectively). In adjusted analyses, having a TTI that was greater than 6 months was associated with only a few aspects of interview responses (e.g., start month of pseudoephedrine use). Interaction by case-control status was observed for some exposures; mothers of controls had a greater reduction in interview quality with increased TTI in these instances (e.g., report of morning sickness, start month of acetaminophen use and ibuprofen use). The results suggest that TTI might impact interview responses; however, the impact may be minimal and specific to the type of exposure.

Systematic review of physiotherapy interventions to improve gross motor capacity and performance in children and adolescents with an acquired brain injury.

PubMed

Baque, Emmah; Sakzewski, Leanne; Barber, Lee; Boyd, Roslyn N

2016-01-01

To systematically review the efficacy of physiotherapy interventions to improve gross motor capacity, performance and societal participation in children aged 5-17 years with an acquired brain injury (ABI). Randomized and non-randomized controlled trials, cohort, case series, case-control and case studies were included and classified according to grades of evidence. Methodological quality of studies was assessed using the Downs and Black (D&B) scale and quantitative data was analysed using effect sizes. Two home-based studies investigated functional strength training (one randomized controlled trial, n = 20, level 2b, D&B = 16/32 and one non-randomized self-control study, n = 19, level 4, D&B = 15/32). Four studies evaluated virtual reality including: one pilot study, n = 50, level 4, D&B = 22/32; one single-subject, non-concurrent, randomized multiple baseline study, n = 3, level 4, D&B = 15/32; one case series study, n = 2, level 4, D&B = 15/32; one case study, n = 1, level 4, D&B = 15/32. Effect sizes for the randomized controlled trial ranged between 0.30-1.29 for the Functional Reach and Timed Up and Go outcome measures. There is preliminary evidence to support the efficacy of physiotherapy interventions to improve gross motor outcomes in children with an ABI. Both functional strength training and virtual-reality based therapy are potential treatment options for clinicians to prescribe in either home or clinical settings.

Crohn's disease and early exposure to domestic refrigeration.

PubMed

Malekzadeh, Fatemeh; Alberti, Corinne; Nouraei, Mehdi; Vahedi, Homayoon; Zaccaria, Isabelle; Meinzer, Ulrich; Nasseri-Moghaddam, Siavosh; Sotoudehmanesh, Rasoul; Momenzadeh, Sara; Khaleghnejad, Reza; Rashtak, Shahrooz; Olfati, Golrokh; Malekzadeh, Reza; Hugot, Jean-Pierre

2009-01-01

Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood. Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD. This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood.

Crohn's Disease and Early Exposure to Domestic Refrigeration

PubMed Central

Malekzadeh, Fatemeh; Alberti, Corinne; Nouraei, Mehdi; Vahedi, Homayoon; Zaccaria, Isabelle; Meinzer, Ulrich; Nasseri-Moghaddam, Siavosh; Sotoudehmanesh, Rasoul; Momenzadeh, Sara; Khaleghnejad, Reza; Rashtak, Shahrooz; Olfati, Golrokh; Malekzadeh, Reza; Hugot, Jean-Pierre

2009-01-01

Background Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood. Methodology/Principal Findings Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01–4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD. Conclusion This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood. PMID:19177167

Baseline Immunoglobulin E Levels as a Marker of Doxorubicin and Trastuzumab-Associated Cardiac Dysfunction

PubMed Central

Beer, Lynn A.; Kossenkov, Andrew V.; Liu, Qin; Luning Prak, Eline; Domchek, Susan; Speicher, David W.; Ky, Bonnie

2016-01-01

Rationale There is a critical need to develop robust, mechanistic strategies to identify patients at increased risk of cancer therapeutics-related cardiac dysfunction (CTRCD). Objective We aimed to discover new biomarkers associated with doxorubicin and trastuzumab-induced CTRCD using high-throughput proteomic profiling. Methods and Results Plasma, echocardiograms, and clinical outcomes were collected at standardized intervals in breast cancer patients undergoing doxorubicin and trastuzumab cancer therapy. Thirty-one longitudinal plasma samples from three cases with CTRCD and four age- and cancer-matched controls without CTRCD were processed and analyzed using label-free liquid chromatography- mass spectrometry (LC-MS). From these analyses, 862 proteins were identified from case/control pairs 1 and 2, and 1,360 proteins from case/control pair 3. Proteins with a greater than 1.5-fold change in cases compared to controls with a p<0.05 either at the time of CTRCD diagnosis or across all timepoints were considered candidate diagnostic or predictive biomarkers, respectively. The protein that demonstrated the largest differences between cases and controls was immunoglobulin E (IgE), with higher levels detected at baseline and across all timepoints in controls without CTRCD as compared to matched CTRCD cases (p<0.05). Similarly, in a validation study of 35 participants treated with doxorubicin and trastuzumab, high baseline IgE levels were associated with a significantly lower risk of CTRCD (p=0.018). Conclusions In patients receiving doxorubicin and trastuzumab, high baseline IgE levels are associated with a lower risk of CTRCD. These novel findings suggest a new paradigm in cardio-oncology, implicating the immune system as a potential mediator of doxorubicin and trastuzumab-induced cardiac dysfunction. PMID:27582370

Absence of Association between Cord Specific Antibody Levels and Severe Respiratory Syncytial Virus (RSV) Disease in Early Infants: A Case Control Study from Coastal Kenya.

PubMed

Nyiro, Joyce Uchi; Sande, Charles Jumba; Mutunga, Martin; Kiyuka, Patience Kerubo; Munywoki, Patrick Kioo; Scott, John Anthony G; Nokes, David James

2016-01-01

The target group for severe respiratory syncytial virus (RSV) disease prevention is infants under 6 months of age. Vaccine boosting of antibody titres in pregnant mothers could protect these young infants from severe respiratory syncytial virus (RSV) associated disease. Quantifying protective levels of RSV-specific maternal antibody at birth would inform vaccine development. A case control study nested in a birth cohort (2002-07) was conducted in Kilifi, Kenya; where 30 hospitalised cases of RSV-associated severe disease were matched to 60 controls. Participants had a cord blood and 2 subsequent 3-monthly blood samples assayed for RSV-specific neutralising antibody by the plaque reduction neutralisation test (PRNT). Two sample paired t test and conditional logistic regression were used in analyses of log2PRNT titres. The mean RSV log2PRNT titre at birth for cases and controls were not significantly different (P = 0.4) and remained so on age-stratification. Cord blood PRNT titres showed considerable overlap between cases and controls. The odds of RSV disease decreased with increase in log2PRNT cord blood titre. There was a 30% reduction in RSV disease per unit increase in log2PRNT titre (<3months age group) but not significant (P = 0.3). From this study, there is no strong evidence of protection by maternal RSV specific antibodies from severe RSV disease. Cord antibody levels show wide variation with considerable overlap between cases and controls. It is likely that, there are additional factors to specific PRNT antibody levels which determine susceptibility to severe RSV disease. In addition, higher levels of neutralizing antibody beyond the normal range may be required for protection; which it is hoped can be achieved by a maternal RSV vaccine.

Is diabetes mellitus a risk factor for venous thromboembolism? A systematic review and meta-analysis of case-control and cohort studies.

PubMed

Gariani, Karim; Mavrakanas, Thomas; Combescure, Christophe; Perrier, Arnaud; Marti, Christophe

2016-03-01

Diabetes mellitus is a well-established risk factor for atherosclerotic disease, but its role in the occurrence of venous thromboembolism (VTE) has not been elucidated. We conducted a meta-analysis of published cohort and case-control studies to assess whether diabetes mellitus is a risk factor for VTE. We systematically searched MEDLINE and EMBASE for case-control and prospective cohort studies assessing association between the risk of venous thromboembolism and diabetes. Odds ratios (OR) from case-control studies were combined while for prospective studies hazard ratios (HR) were combined. Models with random effects were used. Meta-analyses were conducted separately for raw and adjusted measures of association. 24 studies were identified including 10 cohort studies (274,501 patients) and 14 case-control studies (1,157,086 patients). Meta-analysis of the prospective cohort studies demonstrated a significant association between diabetes and VTE (HR 1.60; 95% CI 1.35 to 1.89). This association was no longer present after analysis of multi-adjusted HRs (HR 1.10; 95% CI 0.77 to 1.56). Meta-analysis of case-control studies showed a significant association between diabetes and VTE (OR 1.57; 95%CI 1.17 to 2.12), but this association was no longer present when adjusted ORs were used (OR 1.18; 95%CI 0.89 to 1.56). The increased risk of VTE associated with diabetes mainly results from confounders rather than an intrinsic effect of diabetes on venous thrombotic risk. Therefore, no specific recommendations should apply for the management of diabetic patients at risk for VTE. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

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.

Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma: Univariate and functionally informed multivariate analyses.

PubMed

Vermeulen, Roel; Saberi Hosnijeh, Fatemeh; Bodinier, Barbara; Portengen, Lützen; Liquet, Benoît; Garrido-Manriquez, Javiera; Lokhorst, Henk; Bergdahl, Ingvar A; Kyrtopoulos, Soterios A; Johansson, Ann-Sofie; Georgiadis, Panagiotis; Melin, Beatrice; Palli, Domenico; Krogh, Vittorio; Panico, Salvatore; Sacerdote, Carlotta; Tumino, Rosario; Vineis, Paolo; Castagné, Raphaële; Chadeau-Hyam, Marc; Botsivali, Maria; Chatziioannou, Aristotelis; Valavanis, Ioannis; Kleinjans, Jos C S; de Kok, Theo M C M; Keun, Hector C; Athersuch, Toby J; Kelly, Rachel; Lenner, Per; Hallmans, Goran; Stephanou, Euripides G; Myridakis, Antonis; Kogevinas, Manolis; Fazzo, Lucia; De Santis, Marco; Comba, Pietro; Bendinelli, Benedetta; Kiviranta, Hannu; Rantakokko, Panu; Airaksinen, Riikka; Ruokojarvi, Paivi; Gilthorpe, Mark; Fleming, Sarah; Fleming, Thomas; Tu, Yu-Kang; Lundh, Thomas; Chien, Kuo-Liong; Chen, Wei J; Lee, Wen-Chung; Kate Hsiao, Chuhsing; Kuo, Po-Hsiu; Hung, Hung; Liao, Shu-Fen

2018-04-18

Recent prospective studies have shown that dysregulation of the immune system may precede the development of B-cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case-control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.01-15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) and matched controls. Linear mixed models and partial least square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed model analyses identified associations linking lower levels of fibroblast growth factor-2 (FGF-2 p = 7.2 × 10 -4 ) and transforming growth factor alpha (TGF-α, p = 6.5 × 10 -5 ) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF-2 (p = 7.8 × 10 -7 ), TGF-α (p = 4.08 × 10 -5 ), fractalkine (p = 1.12 × 10 -3 ), monocyte chemotactic protein-3 (p = 1.36 × 10 -4 ), macrophage inflammatory protein 1-alpha (p = 4.6 × 10 -4 ) and vascular endothelial growth factor (p = 4.23 × 10 -5 ). Our results also provided marginal support for already reported associations between chemokines and diffuse large BCL (DLBCL) and cytokines and chronic lymphocytic leukemia (CLL). Case-only analyses showed that Granulocyte-macrophage colony stimulating factor levels were consistently higher closer to diagnosis, which provides further evidence of its role in tumor progression. In conclusion, our study suggests a role of growth-factors in the incidence of MM and of chemokine and cytokine regulation in DLBCL and CLL. © 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

PubMed

Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer R; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A

2015-09-01

Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study.

PubMed

Agua-Agum, Junerlyn; Ariyarajah, Archchun; Aylward, Bruce; Bawo, Luke; Bilivogui, Pepe; Blake, Isobel M; Brennan, Richard J; Cawthorne, Amy; Cleary, Eilish; Clement, Peter; Conteh, Roland; Cori, Anne; Dafae, Foday; Dahl, Benjamin; Dangou, Jean-Marie; Diallo, Boubacar; Donnelly, Christl A; Dorigatti, Ilaria; Dye, Christopher; Eckmanns, Tim; Fallah, Mosoka; Ferguson, Neil M; Fiebig, Lena; Fraser, Christophe; Garske, Tini; Gonzalez, Lice; Hamblion, Esther; Hamid, Nuha; Hersey, Sara; Hinsley, Wes; Jambei, Amara; Jombart, Thibaut; Kargbo, David; Keita, Sakoba; Kinzer, Michael; George, Fred Kuti; Godefroy, Beatrice; Gutierrez, Giovanna; Kannangarage, Niluka; Mills, Harriet L; Moller, Thomas; Meijers, Sascha; Mohamed, Yasmine; Morgan, Oliver; Nedjati-Gilani, Gemma; Newton, Emily; Nouvellet, Pierre; Nyenswah, Tolbert; Perea, William; Perkins, Devin; Riley, Steven; Rodier, Guenael; Rondy, Marc; Sagrado, Maria; Savulescu, Camelia; Schafer, Ilana J; Schumacher, Dirk; Seyler, Thomas; Shah, Anita; Van Kerkhove, Maria D; Wesseh, C Samford; Yoti, Zabulon

2016-11-01

The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola ("cases") were asked if they had exposure to other potential Ebola cases ("potential source contacts") in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO's response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = -0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population.

Availability of safe drinking-water: the answer to cholera outbreak? Nabua, Camarines Sur, Philippines, 2012.

PubMed

De Guzman, Alethea; de los Reyes, Vikki Carr; Sucaldito, Ma Nemia; Tayag, Enrique

2015-01-01

In May 2012, there were increasing diarrhoea cases and deaths reported from Nabua, Camarines Sur to the Philippines event-based surveillance system. An investigation was conducted to identify risk factors and determine transmission dynamics. A suspected case was defined as a resident of Nabua with at least three episodes of watery diarrhoea per day from 16 March to 22 June 2012. A confirmed case was defined as a suspected case positive for Vibrio cholerae. An environmental investigation was conducted and rectal swabs and water samples sent to the national reference laboratory for bacterial isolation. A 1:2 case-control study matching for age and sex was conducted. Data were analysed using Epi Info. There were 309 suspected cases with two deaths, and the most affected age group was children under five years (45%). Eight cases were positive for Vibrio cholerae Ogawa El Tor and one for Non-01. Water samples were positive for faecal coliforms and Aeromonas caviae. The case-control study showed that cases had a higher odds than controls of using unchlorinated water sources (odds ratio [OR] = 3.6; 95% confidence interval [CI]:1.6-8.5) and having toilets located within 20 m of a septic tank (OR = 2.7; 95% CI: 1.4-5.3). In multivariate analysis, the only significant factor was drinking from piped water (OR = 0.21; 95% CI: 0.09-0.49). In this cholera outbreak, drinking-water from unchlorinated wells was a significant risk factor. Future cholera control efforts should include not just improving water and sanitation systems but also intensified behaviour change campaigns.

A 26-year review of emergency peripartum hysterectomy in a tertiary teaching hospital in Kuwait - years 1983-2011.

PubMed

Chibber, Rachana; Al-Hijji, Jassim; Fouda, Mohamed; Al-Saleh, Eyad; Al-Adwani, Abdul Razzak; Mohammed, Asiya Tasneem

2012-01-01

To identify the risk factors and study the incidence, indications and complications of emergency peripartum hysterectomy (EPH). This was a retrospective case-control study. The cases consisted of all women who underwent EPH between January 1983 and January 2011. Two controls per case were randomly selected from the remaining deliveries by using a random number table. Case records were retrieved from the medical records. Among 150,993 deliveries, there were 59 EPHs (cases), giving a rate of 0.390 per 1,000. Of the 59 cases, only 56 were analysed because 3 files were unavailable. These women were older (mean age 36 ± 5.7 vs. 22 ± 5.3 years, p < 0.01) and had delivered more than 1 child (p = 0.02). Thirty-seven (66%) cases had had previous caesarean sections (CSs) and the number of CSs in this group was greater than in the controls (21%, p < 0.01). More index cases had a history of atonic postpartum haemorrhage (46 vs. 4%, p < 0.001) and placenta praevia (34 vs. 4%, p < 0.01). More cases than controls were delivered by CS (73 vs. 29%; p = 0.003). The leading indications for EPH were haemorrhage due to uterine atony and placenta praevia. Independent risk factors were older age, multiparity, history of one or more CSs and placenta praevia. There were 2 maternal deaths from coagulopathy following massive obstetric haemorrhage. The main complications of EPH were febrile morbidity: 12 (21%), wound infection: 8 (14%) and bladder or ureteric injury: 8 (14%). CSs, especially repeat CSs in women with placenta praevia and persistent uterine atony, significantly increased the risks of peripartum hysterectomy. Copyright © 2011 S. Karger AG, Basel.

Dairy products and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition.

PubMed

Duarte-Salles, Talita; Fedirko, Veronika; Stepien, Magdalena; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Lukanova, Annekatrin; Trepo, Elisabeth; Overvad, Kim; Tjønneland, Anne; Halkjaer, Jytte; Boutron-Ruault, Marie-Christine; Racine, Antoine; Cadeau, Claire; Kühn, Tilman; Aleksandrova, Krasimira; Trichopoulos, Dimitrios; Tsiotas, Konstantinos; Boffetta, Paolo; Palli, Domenico; Pala, Valeria; Tumino, Rosario; Sacerdote, Carlotta; Panico, Salvatore; Bueno-de-Mesquita, H B as; Dik, Vincent K; Peeters, Petra H; Weiderpass, Elisabete; Torhild Gram, Inger; Hjartåker, Anette; Ramón Quirós, Jose; Fonseca-Nunes, Ana; Molina-Montes, Esther; Dorronsoro, Miren; Navarro Sanchez, Carmen; Barricarte, Aurelio; Lindkvist, Björn; Sonestedt, Emily; Johansson, Ingegerd; Wennberg, Maria; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth C; Romieu, Isabelle; Riboli, Elio; Jenab, Mazda

2014-10-01

Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/yogurt) and their components (calcium/vitamin D/fats/protein), with first incident HCC (N(cases) = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (N(cases) = 122) with the assessment of hepatitis B virus/hepatitis C virus infections status, liver damage and circulating insulin-like growth factor (IGF)-I levels. For cohort analyses, multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% CI. A total of 477,206 participants were followed-up for an average of 11 years (person-years follow-up = 5,415,385). In the cohort study, a significant positive HCC risk association was observed for total dairy products (highest vs. lowest tertile, HR = 1.66, 95% CI: 1.13-2.43; p(trend) = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; p(trend) = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; p(trend) = 0.101), but not yogurt (HR = 0.94, 95% CI: 0.65-1.35). Dietary calcium, vitamin D, fat and protein from dairy sources were associated with increased HCC risk, whereas the same nutrients from nondairy sources showed inverse or null associations. In the nested case-control study, similar results were observed among hepatitis-free individuals. Results from this large prospective cohort study suggest that higher consumption of dairy products, particularly milk and cheese, may be associated with increased HCC risk. Validation of these findings in other populations is necessary. Potential biologic mechanisms require further exploration. © 2014 UICC.

Infertility and Its Treatments in Association with Autism Spectrum Disorders: A Review and Results from the CHARGE Study

PubMed Central

Lyall, Kristen; Baker, Alice; Hertz-Picciotto, Irva; Walker, Cheryl K.

2013-01-01

Previous findings on relationships between infertility, infertility therapies, and autism spectrum disorders (ASD) have been inconsistent. The goals of this study are first, to briefly review this evidence and second, to examine infertility and its treatments in association with having a child with ASD in newly analyzed data. In review, we identified 14 studies published as of May 2013 investigating infertility and/or its treatments and ASD. Overall, prior results showed little support for a strong association, though some increases in risk with specific treatments were found; many limitations were noted. In new analyses of the CHildhood Autism Risk from Genetics and the Environment (CHARGE) population-based study, cases with autism spectrum disorder (ASD, n = 513) and controls confirmed to have typical development (n = 388) were compared with regard to frequencies of infertility diagnoses and treatments overall and by type. Infertility diagnoses and treatments were also grouped to explore potential underlying pathways. Logistic regression was used to obtain crude and adjusted odds ratios overall and, in secondary analyses, stratified by maternal age (≥35 years) and diagnostic subgroups. No differences in infertility, infertility treatments, or hypothesized underlying pathways were found between cases and controls in crude or adjusted analyses. Numbers were small for rarer therapies and in subgroup analyses; thus the potential for modest associations in specific subsets cannot be ruled out. However, converging evidence from this and other studies suggests that assisted reproductive technology is not a strong independent risk factor for ASD. Recommendations for future studies of this topic are provided. PMID:23965925

Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and rheumatoid arthritis.

PubMed

Ball, Robert J; Avenell, Alison; Aucott, Lorna; Hanlon, Peter; Vickers, Mark A

2015-09-29

Infection with Epstein-Barr virus (EBV) has been suggested to contribute to the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). We sought to determine whether prior infection with the virus occurs more frequently in patients with RA compared to controls. We performed a systematic review and meta-analyses of studies that reported the prevalence of anti-EBV antibodies in the sera of cases with RA and controls by searching Medline and Embase databases from 1946 to 2014, with no language restriction. Mantel-Haenszel odds ratios for the detection of anti-EBV antibodies were calculated, and meta-analyses conducted. Quality assessments were performed using a modified version of the Newcastle-Ottawa scale. Twenty-three studies were included. Quality assessment found most studies reported acceptable selection criteria but poor descriptions of how cases and controls were recruited. When all studies were included, there was a statistically significant higher seroprevalence of anti-VCA IgG in patients with RA compared to controls with an odds ratio (OR) of 1.61 (95 % confidence interval (CI) 1.05-2.46, p = 0.03), which is a similar-sized summary OR to that reported for systemic lupus erythematosus (SLE). However, when studies were restricted to those reporting more plausible levels of exposure to EBV in the control groups, no significant association was apparent, OR 1.47 (95 % CI 0.88-2.46, p = 0.14). Using anti-EBNA 1 or anti-EA IgG as markers of previous infection also did not yield significant associations (OR 1.05, 95 % CI 0.68-1.61, p = 0.82; OR 2.2, 95 % CI 0.86-5.65, p = 0.10 respectively). Overall, these findings do not demonstrate an association between EBV seroprevalence and RA and therefore do not support the hypothesis that prior infection with EBV predisposes to the development of RA. This contrasts with meta-analyses that indicate EBV infection is associated with multiple sclerosis and SLE.

Multilocus family-based association analysis of seven candidate polymorphisms with essential hypertension in an african-derived semi-isolated brazilian population.

PubMed

Kimura, L; Angeli, C B; Auricchio, M T B M; Fernandes, G R; Pereira, A C; Vicente, J P; Pereira, T V; Mingroni-Netto, R C

2012-01-01

Background. It has been widely suggested that analyses considering multilocus effects would be crucial to characterize the relationship between gene variability and essential hypertension (EH). Objective. To test for the presence of multilocus effects between/among seven polymorphisms (six genes) on blood pressure-related traits in African-derived semi-isolated Brazilian populations (quilombos). Methods. Analyses were carried out using a family-based design in a sample of 652 participants (97 families). Seven variants were investigated: ACE (rs1799752), AGT (rs669), ADD2 (rs3755351), NOS3 (rs1799983), GNB3 (rs5441 and rs5443), and GRK4 (rs1801058). Sensitivity analyses were further performed under a case-control design with unrelated participants only. Results. None of the investigated variants were associated individually with both systolic and diastolic BP levels (SBP and DBP, respectively) or EH (as a binary outcome). Multifactor dimensionality reduction-based techniques revealed a marginal association of the combined effect of both GNB3 variants on DBP levels in a family-based design (P = 0.040), whereas a putative NOS3-GRK4 interaction also in relation to DBP levels was observed in the case-control design only (P = 0.004). Conclusion. Our results provide limited support for the hypothesis of multilocus effects between/among the studied variants on blood pressure in quilombos. Further larger studies are needed to validate our findings.

The Ukrainian-American Study of Leukemia and Related Disorders Among Chornobyl Cleanup Workers from Ukraine: I. STUDY METHODS

PubMed Central

Romanenko, A.; Bebeshko, V; Hatch, M; Bazyka, D; Finch, S.; Dyagil, I; Reiss, R.; Chumak, V; Bouville, A; Gudzenko, N; Zablotska, L; Pilinskaya, M.; Lyubarets, T.; Bakhanova, E.; Babkina, N.; Trotsiuk, N.; Ledoschuk, B.; Belayev, Y.; Dybsky, S.S.; Ron, E.; Howe, G.

2010-01-01

Thus far there are relatively few data on the risk of leukemia among those who were exposed to external radiation during cleanup operations following the Chornobyl nuclear accident, and results have not been consistent. To investigate this issue further, we assembled a cohort of 110,645 male cleanup workers from Ukraine and identified cases of leukemia occurring during the period 1986 to 2000. Detailed interviews were conducted and individual bone marrow doses were estimated using a new time-and-motion method known as RADRUE (Realistic Analytical Dose Reconstruction with Uncertainty Estimate). See companion paper II for a detailed description of the dosimetry. For the initial analyses we used a nested case-control approach with a minimum of five controls per case, matched for year of birth, oblast (region) of registration and residence. All identified cases were reviewed by an international panel of experts. The dose-response analysis and results are given in companion paper III. PMID:19138036

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

Kenneth, O., E-mail: kenneth@physics.technion.ac.il; Avron, J.E.

Aharonov and Casher showed that Pauli Hamiltonians in two dimensions have gapless zero modes. We study the adiabatic evolution of these modes under the slow motion of N fluxons with fluxes Φ{sub a}∈R. The positions, r{sub a}∈R{sup 2}, of the fluxons are viewed as controls. We are interested in the holonomies associated with closed paths in the space of controls. The holonomies can sometimes be abelian, but in general are not. They can sometimes be topological, but in general are not. We analyse some of the special cases and some of the general ones. Our most interesting results concern themore » cases where holonomy turns out to be topological which is the case when all the fluxons are subcritical, Φ{sub a}<1, and the number of zero modes is D=N−1. If N≥3 it is also non-abelian. In the special case that the fluxons carry identical fluxes the resulting anyons satisfy the Burau representations of the braid group.« less

Glioma and occupational exposure in Sweden, a case-control study.

PubMed Central

Rodvall, Y; Ahlbom, A; Spännare, B; Nise, G

1996-01-01

OBJECTIVES: The aim of the study was to analyse whether any job titles, industrial codes, and certain occupational exposures were associated with an increased risk of glioma. METHODS: A population based case-control study of incident primary brain tumours in adults was carried out in Uppsala, Sweden in the period 1987-90. The study included 192 cases of glioma and 192 matched controls. It also included cases with other tumours of the central nervous system with matched controls. Information from all 343 controls was used in this study. Information was collected by means of a questionnaire that was sent to all subjects. An occupational hygienist reviewed the questionnaires for self reported exposures to substances and assessed whether these reported exposures were plausible or not in the corresponding occupation. RESULTS: The kappa coefficient for those classified by the two methods ranged between 0.46 and 0.88, and they were almost the same for cases and controls. For men exposed to solvents a relative risk (RR) of 2.6 (95% CI 1.3 to 5.2) was found. For men exposed to pesticides the RR was 1.8 (95% CI 0.6 to 5.1), and for plastic materials the RR was 3.6 (95% CI 1.0 to 12.4). For men employed in forestry and logging the RR was 2.2 (95% CI 0.9 to 5.3) and in basic metal industries 2.0 (95% CI 1.0 to 4.0). CONCLUSION: An increased risk of glioma was associated with use of solvents, pesticides, and plastic materials but this should be interpreted with some caution. PMID:8983463

Effect of incorporating a 10 minute point of care test for salivary nicotine metabolites into a general practice based smoking cessation programme: randomised controlled trial.

PubMed

Barnfather, Kristian D; Cope, Graham F; Chapple, Iain L

2005-10-29

To investigate the effect of immediate feedback from a point of care test for salivary nicotine metabolites in promoting smoking cessation and reduction in tobacco use. Prospective, operator blinded, randomised controlled trial. General dental practice, London. 100 adult smokers. Participants completed a questionnaire on smoking, undertook a clinical examination, and received counselling in smoking cessation. Saliva samples were analysed at presentation and at eight weeks for salivary nicotine metabolites using a 10 minute semiquantitative point of care test. Smoking cessation measured by salivary nicotine metabolite values (scale 0-6), patient feedback on the perceived value of the test (visual analogue scale) in quitting, and reduction in tobacco use. A higher smoking quit rate was achieved with the point of care test (23% cases v 7% controls; P < 0.039), and overall tobacco use also decreased (68% cases v 28% controls; P < 0.001). Baseline values for salivary nicotine metabolites did not differ between the groups (cases, mean 4.1, SD 1.3 and 4.3, 1.4; P = 0.51). 87 participants reattended at eight weeks (44 cases, 43 controls). Mean nicotine metabolite values at eight weeks were 2.58 (2.0) for cases and 4.29 (1.8) for controls (P < 0.001). Incorporation of individualised personal feedback using a point of care test for salivary nicotine metabolites into a general practice based smoking cessation programme increased quit rates by 17% at eight weeks and reduced tobacco use.

Clinical Perspectives of Genetic Analyses on Dyslipidemia and Coronary Artery Disease

PubMed Central

Kawashiri, Masa-aki; Yamagishi, Masakazu

2017-01-01

We have learned that low-density lipoprotein (LDL) cholesterol is the cause of atherosclerosis from various aspects, including a single case with familial hypercholesterolemia, other cases with different types of Mendelian dyslipidemias, large-scale randomized controlled trials using LDL cholesterol lowering therapies, and Mendelian randomization studies using common as well as rare variants associated with LDL cholesterol levels. There is no doubt that determinations of genotypes in lipid-associated genes have contributed not only to the genetic diagnosis for Mendelian dyslipidemias but also to the discoveries of novel therapeutic targets. Furthermore, recent studies have shown that such genetic information could provide useful clues for the risk prediction as well as risk stratification in general and in particular population. We provide the current understanding of genetic analyses relating to plasma lipids and coronary artery disease. PMID:28250266

Effects of a 3-year nurse-based case management in aged patients with acute myocardial infarction on rehospitalisation, mortality, risk factors, physical functioning and mental health. a secondary analysis of the randomized controlled KORINNA study.

PubMed

Kirchberger, Inge; Hunger, Matthias; Stollenwerk, Björn; Seidl, Hildegard; Burkhardt, Katrin; Kuch, Bernhard; Meisinger, Christa; Holle, Rolf

2015-01-01

Home-based secondary prevention programs led by nurses have been proposed to facilitate patients' adjustment to acute myocardial infarction (AMI). The objective of this study was to conduct secondary analyses of the three-year follow-up of a nurse-based case management for elderly patients discharged from hospital after an AMI. In a single-centre randomized two-armed parallel group trial of hospitalized patients with AMI ≥65 years, patients hospitalized between September 2008 and May 2010 in the Hospital of Augsburg, Germany, were randomly assigned to case management or usual care. The case-management intervention consisted of a nurse-based follow-up for three years including home visits and telephone calls. Study endpoints were time to first unplanned readmission or death, clinical parameters, functional status, depressive symptoms and malnutrition risk. Persons who assessed three-year outcomes and validated readmission data were blinded. The intention-to-treat approach was applied to the statistical analyses which included Cox Proportional Hazards models. Three hundred forty patients were allocated to receive case-management (n = 168) or usual care (n = 172). During three years, in the intervention group there were 80 first unplanned readmissions and 6 deaths, while the control group had 111first unplanned readmissions and 3 deaths. The intervention did not significantly affect time to first unplanned readmission or death (Hazard Ratio 0.89, 95% confidence interval (CI) 0.67-1.19; p = 0.439), blood pressure, cholesterol level, instrumental activities of daily life (IADL) (only for men), and depressive symptoms. However, patients in the intervention group had a significantly better functional status, as assessed by the HAQ Disability Index, IADL (only for women), and hand grip strength, and better SCREEN-II malnutrition risk scores than patients in the control group. A nurse-based management among elderly patients with AMI did not significantly affect time to unplanned readmissions or death during a three-year follow-up. However, the results indicate that functional status and malnutrition risk can be improved. Current Controlled Trials ISRCTN02893746.

Tramadol use and the risk of hospitalization for hypoglycemia in patients with noncancer pain.

PubMed

Fournier, Jean-Pascal; Azoulay, Laurent; Yin, Hui; Montastruc, Jean-Louis; Suissa, Samy

2015-02-01

Tramadol is a weak opioid analgesic whose use has increased rapidly, and it has been associated with adverse events of hypoglycemia. To assess whether tramadol use, when compared with codeine use, is associated with an increased risk of hospitalization for hypoglycemia. A nested case-control analysis was conducted within the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database of all patients newly treated with tramadol or codeine for noncancer pain between 1998 and 2012. Cohort and case-crossover analyses were also conducted to assess consistency of the results. Cases of hospitalization for hypoglycemia were matched with up to 10 controls on age, sex, and duration of follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated comparing use of tramadol with codeine. A cohort analysis, with high-dimensional propensity score-adjusted hazard ratios (HRs) and 95% CIs, was performed comparing tramadol with codeine in the first 30 days after treatment initiation. Finally, a case-crossover analysis was also performed, in which exposure to tramadol in a 30-day risk period immediately before the hospitalization for hypoglycemia was compared with 11 consecutive 30-day control periods. Odds ratios and 95% CIs were estimated using conditional logistic regression analysis. The cohort included 334,034 patients, of whom 1105 were hospitalized for hypoglycemia during follow-up (incidence, 0.7 per 1000 per year) and matched to 11,019 controls. Compared with codeine, tramadol use was associated with an increased risk of hospitalization for hypoglycemia (OR, 1.52 [95% CI, 1.09-2.10]), particularly elevated in the first 30 days of use (OR, 2.61 [95% CI, 1.61-4.23]). This 30-day increased risk was confirmed in the cohort (HR, 3.60 [95% CI, 1.56-8.34]) and case-crossover analyses (OR, 3.80 [95% CI, 2.64-5.47]). The initiation of tramadol therapy is associated with an increased risk of hypoglycemia requiring hospitalization. Additional studies are needed to confirm this rare but potentially fatal adverse event.

Is work organisation associated with work status 3 months after injury? Results from a case-control study of New Zealand workers.

PubMed

Lilley, Rebbecca; Derrett, Sarah; Davie, Gabrielle

2015-01-01

Little empirical examination of the relationship between work organisational factors and return to work following injury has been undertaken despite the growing recognition of examining broader multi-dimensional contexts for recovery following injury. To explore relationships between pre-injury work organisational factors and work status (working/work absent) 3-month after injury among people employed prior to injury. Cases (work absent) and controls (working), selected from a larger study of injury outcomes according to reported work status 3-month after injury, completed a postal questionnaire. Work organisational factors were compared between cases and controls using univariate and multivariable analyses. One hundred and twelve participants completed the questionnaire (44 cases; 68 controls). Of 11 work organisation factors examined, organisational size was the only explanatory variable significantly associated with work status in the multivariable model. Higher odds of work absence were found in small (< 50 employees) (OR 5.6) and large (> 500 employees) (OR 7.2) workplaces, compared with medium-sized (50-500 employees) organisations. Variations in post-injury work patterns among those working pre-injury may be partly explained by organisation size. Future research examining work status following injury should examine the influence of work organisational factors in larger studies.

Development, Validation, and Fairness of a Biographical Data Questionnaire for the Air Traffic Control Specialist Occupation

DTIC Science & Technology

2012-12-01

Development and validation. ABA, BQ , and criterion data were extracted from AT- SAT concurrent, criterion- related validation database. Overall, 1,232...dependent on responses to the other instrument. 3 A subset of 260 controllers in the AT- SAT dataset had full and complete ABA, BQ , and criterion data (i.e... SAT cases with ABA, BQ , and criterion data (n=260) was very small, making fairness analyses with the validation sample impractical. However, the

Ecology of rabies in Southern Rhodesia.

PubMed

ADAMSON, J S

1954-01-01

The spread of rabies since 1950 in Southern Rhodesia is described, and its probable causes analysed; the outbreak is attributed chiefly to the vast domestic-dog population, but cases have been noted among many other species of animal. The difficulties encountered in enforcing general control measures are discussed; however, the advent of Flury-strain avianized vaccine has allowed of a successful inoculation campaign which, in spite of some failure in immunization, is satisfactorily controlling the disease in most of the areas involved.

Ecology of rabies in Southern Rhodesia

PubMed Central

Adamson, J. S.

1954-01-01

The spread of rabies since 1950 in Southern Rhodesia is described, and its probable causes analysed; the outbreak is attributed chiefly to the vast domestic-dog population, but cases have been noted among many other species of animal. The difficulties encountered in enforcing general control measures are discussed; however, the advent of Flury-strain avianized vaccine has allowed of a successful inoculation campaign which, in spite of some failure in immunization, is satisfactorily controlling the disease in most of the areas involved. PMID:13182596

Fracture and failure: Analyses, mechanisms and applications; Proceedings of the Symposium, Los Angeles, CA, March 17-20, 1980

NASA Technical Reports Server (NTRS)

Tung, P. P. (Editor); Agrawal, S. P.; Kumar, A.; Katcher, M.

1981-01-01

Papers are presented on the application of fracture mechanics to spacecraft design, fracture control applications on the Space Shuttle reaction control thrusters, and an assessment of fatigue crack growth rate relationships for metallic airframe materials. Also considered are fracture mechanisms and microstructural relationships in Ni-base alloy systems, the use of surface deformation markings to determine crack propagation directions, case histories of metallurgical failures in the electronics industry, and a failure analysis of silica phenolic nozzle liners.

Phenoxy herbicides and chlorophenols: a case control study on soft tissue sarcoma and malignant lymphoma.

PubMed Central

Smith, J. G.; Christophers, A. J.

1992-01-01

A case control study on patients with soft tissue sarcoma and malignant lymphoma was undertaken to test whether there was any association between these diseases and past exposure to chlorinated phenoxy acid herbicides or chlorophenols. It was carried out over the period 1982-1988 in Victoria, Australia. Thirty males with soft tissue sarcoma and 52 males with malignant lymphoma were matched by age, place of residence and sex with one population control and one cancer control each. Exposure was assessed by personal interviews conducted by an occupational hygienist. Exposures within 5 years prior to diagnosis of each matched case were ignored, both for the cases and their matched controls. The estimated relative risks for definite or probable exposure to chlorinated phenoxy compounds or chlorophenols for at least 1 day were 1.0 (95% confidence interval (CI): 0.3-3.1) for soft tissue sarcoma and 1.5 (95% CI: 0.6-3.7) for malignant lymphoma. When the criterion for exposure was raised to more than 30 days, the estimated relative risks were 2.0 (95% CI: 0.5-8.0) for soft tissue sarcoma and 2.7 (95% CI: 0.7-9.6) for malignant lymphoma. Additional analyses were carried out for exposure of at least 1 day to phenoxy herbicides alone or chlorophenols alone. None of the estimated relative risks was significantly greater than unity. PMID:1558802

A case-control comparison of direct healthcare-provider medical costs of chronic idiopathic constipation and irritable bowel syndrome with constipation in a community-based cohort

PubMed Central

Herrick, Linda M.; Spalding, William M.; Saito, Yuri A.; Moriarty, James; Schleck, Cathy

2017-01-01

Objective Patients with constipation account for 3.1 million United States physician visits a year, but care costs for patients with irritable bowel syndrome with constipation (IBS-C) or chronic idiopathic constipation (CIC) compared to the general public have received little study. The study aim was to describe healthcare utilization and compare medical costs for patients with IBS-C or CIC versus matched controls from a community-based sample. Methods A nested case-control sample (IBS-C and CIC cases) and matched controls (1:2) for each case group were selected from Olmsted County, MN individuals responding to a community-based survey of gastrointestinal symptoms (2008) who received healthcare from a participating Rochester Epidemiology Project (REP) provider. Using REP healthcare utilization data, unadjusted and adjusted standardized costs were compared for the 2- and 10-year periods prior to the survey for 115 IBS-C patients and 230 controls and 365 CIC patients and 730 controls. Two time periods were chosen as these conditions are episodic but long-term. Results Outpatient costs for IBS-C ($6,800) and CIC ($6,284) patients over a 2-year period prior to the survey were significantly higher than controls ($4,242 and $5,254 respectively) after adjusting for co-morbidities, age, and sex. IBS-C outpatient costs ($25,448) and emergency room costs ($6,892) were significantly higher than controls ($21,024 and $3,962 respectively) for the 10-year period prior. Unadjusted data analyses of cases compared to controls demonstrated significantly higher imaging costs for IBS-C cases and procedure costs for CIC cases over the 10-year period. Limitations Data were collected from a random community sample primarily receiving care from a limited number of providers in that area. Conclusions Patients with IBS-C and CIC had significantly higher outpatient costs for the 2-year period compared with controls. IBS-C patients also had higher ER costs than the general population. PMID:27783533

Risk factors for hematemesis in Hoima and Buliisa Districts, Western Uganda, September-October 2015.

PubMed

Kabwama, Steven Ndugwa; Mafigiri, Richardson; Balinandi, Stephen; Kagirita, Atek; Riolexus, Alex Ario; Zhu, Bao-Ping

2017-01-01

On 17 September 2015, Buliisa District Health Office reported multiple deaths due to haemorrhage to the Uganda Ministry of Health. We conducted an investigation to verify the existence of an outbreak and to identify the disease nature, mode of transmission and risk factors. We defined a suspected case as onset of hematemesis between 1 June 2015 and 15 October 2015 in a resident of Hoima, Buliisa or neighbouring districts. We identified cases by reviewing medical records and actively searching in the community. We interviewed case-patients and health-care workers and performed descriptive epidemiology to generate hypotheses on possible exposures. In a case-control study we compared exposures between 21 cases and 81 controls, matched by age (± 10 years), sex and village of residence. We collected 22 biological specimens from 19 case-patients to test for Viral Haemorrhagic Fevers (VHF). We analysed the data using the Mantel-Haenszel method to account for the matched study design. We identified 56 cases with onset from June to October (attack rate 15/100,000 in Buliisa District and 5.2/100,000 in Hoima District). The age-specific attack rate was highest in persons aged 31-60 years (15/100,000 in Hoima and 47/100,000 in Buliisa); no persons below 15 years of age had the illness. In the case-control study, 42% (5/12) of cases vs. 0.0% (0/77) of controls had liver disease (OR M-H = ∞; 95%CI = 3.7-∞); 71% (10/14) of cases vs. 35% (28/81) of controls had ulcer disease (OR M-H = 13; 95% CI = 1.6-98); 27% (3/11) of cases vs. 14% (11/81) of controls used indomethacin prior to disease onset (OR M-H = 6.0; 95% CI = 1.0-36). None of the blood samples were positive for any of the VHFs. This reported cluster of hematemesis illness was due to predisposing conditions and use of Non-Steroidal Anti-inflammatory Drugs (NSAID). Health education should be conducted on the danger of NSAIDs misuse, especially in persons with pre-disposing conditions.

Power and Control: Managing Agents for International Student Recruitment in Higher Education

ERIC Educational Resources Information Center

Huang, Iona Yuelu; Raimo, Vincenzo; Humfrey, Christine

2016-01-01

This multiple case-based study investigates the relationship between recruiting agents and the UK universities who act as their principals. The current extensive use of agents in UK higher education may be seen as an indicator of the financial impact made by international students. The study analyses the practice of agent management and explores…

Integrating GIS in the Middle School Curriculum: Impacts on Diverse Students' Standardized Test Scores

ERIC Educational Resources Information Center

Goldstein, Donna; Alibrandi, Marsha

2013-01-01

This case study conducted with 1,425 middle school students in Palm Beach County, Florida, included a treatment group receiving GIS instruction (256) and a control group without GIS instruction (1,169). Quantitative analyses on standardized test scores indicated that inclusion of GIS in middle school curriculum had a significant effect on student…

Single-Case Experimental Designs in Educational Research: A Methodology for Causal Analyses in Teaching and Learning

ERIC Educational Resources Information Center

Plavnick, Joshua B.; Ferreri, Summer J.

2013-01-01

Current legislation requires educational practices be informed by science. The effort to establish educational practices supported by science has, to date, emphasized experiments with large numbers of participants who are randomly assigned to an intervention or control condition. A potential limitation of such an emphasis at the expense of other…

Speed limiter integrated fatigue analyzer (SLIFA) for speed and fatigue control on diesel engine truck and bus

NASA Astrophysics Data System (ADS)

Wahyudi, Haris; Pranoto, Hadi; Leman, A. M.; Sebayang, Darwin; Baba, I.

2017-09-01

Every second, the number of road traffic deaths is increased globally with millions more sustaining severe injuries and living with long-term adverse health consequences. Jakarta alone in year 2015 had recorded 556 people died due to road accidents, approximately reached 6.231 road accident cases. The identified major contributory factors of such unfortunate events are both driver fatigue and over speeding habit especially related to the driving of truck and bus. This paper presents the idea on how to control the electronic system from input fuel system of injection pump and the combustion chamber engine will control the valve solenoid in injection pump which can lock and fuel will stop for moment, and speed limit can be success, by using sensor heart rate we can input reduce speed limit when fatigue detection driver. Integration process this tool can be relevant when Speed Limiter Integrated Fatigue Analyser (SLIFA) trial in the diesel engine for truck and bus, the result of this research Speed Limiter Integrated Fatigue Analyser (SLIFA) able to control speed of diesel engine for truck and bus almost 30km/h, 60km/h, and until 70 km/h. The installation of the sensor heart rate as the input speed limit SLIFA would work when the driver is detected to be in the fatigue condition. We make Speed Limiter Integrated Fatigue Analyser (SLIFA) for control and monitoring system for diesel engine in truck and bus. Speed Limiter Integrated Fatigue Analyser (SLIFA) system can save the historical of the speed record, fatigue, rpm, and body temperature of the driver.

Guiding principles for vortex flow controls

NASA Technical Reports Server (NTRS)

Wu, J. Z.; Wu, J. M.

1991-01-01

In the practice of vortex flow controls, the most important factor is that the persistency and obstinacy of a concentrated vortex depend on its stability and dissipation. In this paper, the modern nonlinear stability theory for circulation-preserving flows is summarized, and the dissipation for general viscous flows is analyzed in terms of the evolution of total enstrophy. These analyses provide a theoretical base for understanding relevant physics of vortex flows, and lead to some guiding principles and methods for their controls. Case studies taken from various theoretical and/or experimental works of vortex controls, due to the present authors as well as others, confirm the feasibility of the recommended principles and methods.

A large Legionnaires' disease outbreak in Pamplona, Spain: early detection, rapid control and no case fatality

PubMed Central

CASTILLA, J.; BARRICARTE, A.; ALDAZ, J.; GARCÍA CENOZ, M.; FERRER, T.; PELAZ, C.; PINEDA, S.; BALADRÓN, B.; MARTÍN, I.; GOÑI, B.; ARATAJO, P.; CHAMORRO, J.; LAMEIRO, F.; TORROBA, L.; DORRONSORO, I.; MARTÍNEZ-ARTOLA, V.; ESPARZA, M. J.; GASTAMINZA, M. A.; FRAILE, P.; ALDAZ, P.

2008-01-01

SUMMARY An outbreak of Legionnaire's disease was detected in Pamplona, Spain, on 1 June 2006. Patients with pneumonia were tested to detect Legionella pneumophila antigen in urine (Binax Now; Binax Inc., Scarborough, ME, USA), and all 146 confirmed cases were interviewed. The outbreak was related to district 2 (22 012 inhabitants), where 45% of the cases lived and 50% had visited; 5% lived in neighbouring districts. The highest incidence was found in the resident population of district 2 (3/1000 inhabitants), section 2 (14/1000). All 31 cooling towers of district 2 were analysed. L. pneumophila antigen (Binax Now) was detected in four towers, which were closed on 2 June. Only the strain isolated in a tower situated in section 2 of district 2 matched all five clinical isolates, as assessed by mAb and two genotyping methods, AFLP and PFGE. Eight days after closing the towers, new cases ceased appearing. Early detection and rapid coordinated medical and environmental actions permitted immediate control of the outbreak and probably contributed to the null case fatality. PMID:17662166

A large Legionnaires' disease outbreak in Pamplona, Spain: early detection, rapid control and no case fatality.

PubMed

Castilla, J; Barricarte, A; Aldaz, J; García Cenoz, M; Ferrer, T; Pelaz, C; Pineda, S; Baladrón, B; Martín, I; Goñi, B; Aratajo, P; Chamorro, J; Lameiro, F; Torroba, L; Dorronsoro, I; Martínez-Artola, V; Esparza, M J; Gastaminza, M A; Fraile, P; Aldaz, P

2008-06-01

An outbreak of Legionnaire's disease was detected in Pamplona, Spain, on 1 June 2006. Patients with pneumonia were tested to detect Legionella pneumophila antigen in urine (Binax Now; Binax Inc., Scarborough, ME, USA), and all 146 confirmed cases were interviewed. The outbreak was related to district 2 (22 012 inhabitants), where 45% of the cases lived and 50% had visited; 5% lived in neighbouring districts. The highest incidence was found in the resident population of district 2 (3/1000 inhabitants), section 2 (14/1000). All 31 cooling towers of district 2 were analysed. L. pneumophila antigen (Binax Now) was detected in four towers, which were closed on 2 June. Only the strain isolated in a tower situated in section 2 of district 2 matched all five clinical isolates, as assessed by mAb and two genotyping methods, AFLP and PFGE. Eight days after closing the towers, new cases ceased appearing. Early detection and rapid coordinated medical and environmental actions permitted immediate control of the outbreak and probably contributed to the null case fatality.

Exposure Patterns Driving Ebola Transmission in West Africa: A Retrospective Observational Study

PubMed Central

Agua-Agum, Junerlyn; Aylward, Bruce; Bawo, Luke; Blake, Isobel M.; Brennan, Richard J.; Cawthorne, Amy; Cleary, Eilish; Clement, Peter; Conteh, Roland; Cori, Anne; Dafae, Foday; Dahl, Benjamin; Dangou, Jean-Marie; Diallo, Boubacar; Donnelly, Christl A.; Dye, Christopher; Eckmanns, Tim; Fallah, Mosoka; Fiebig, Lena; Fraser, Christophe; Garske, Tini; Gonzalez, Lice; Hamblion, Esther; Hamid, Nuha; Hinsley, Wes; Jambei, Amara; Jombart, Thibaut; Kargbo, David; Keita, Sakoba; Kinzer, Michael; George, Fred Kuti; Godefroy, Beatrice; Gutierrez, Giovanna; Kannangarage, Niluka; Mills, Harriet L.; Moller, Thomas; Meijers, Sascha; Mohamed, Yasmine; Newton, Emily; Nouvellet, Pierre; Nyenswah, Tolbert; Perea, William; Perkins, Devin; Riley, Steven; Rondy, Marc; Sagrado, Maria; Savulescu, Camelia; Schafer, Ilana J.; Schumacher, Dirk; Seyler, Thomas; Shah, Anita; Van Kerkhove, Maria D.; Wesseh, C. Samford; Yoti, Zabulon

2016-01-01

Background The ongoing West African Ebola epidemic began in December 2013 in Guinea, probably from a single zoonotic introduction. As a result of ineffective initial control efforts, an Ebola outbreak of unprecedented scale emerged. As of 4 May 2015, it had resulted in more than 19,000 probable and confirmed Ebola cases, mainly in Guinea (3,529), Liberia (5,343), and Sierra Leone (10,746). Here, we present analyses of data collected during the outbreak identifying drivers of transmission and highlighting areas where control could be improved. Methods and Findings Over 19,000 confirmed and probable Ebola cases were reported in West Africa by 4 May 2015. Individuals with confirmed or probable Ebola (“cases”) were asked if they had exposure to other potential Ebola cases (“potential source contacts”) in a funeral or non-funeral context prior to becoming ill. We performed retrospective analyses of a case line-list, collated from national databases of case investigation forms that have been reported to WHO. These analyses were initially performed to assist WHO’s response during the epidemic, and have been updated for publication. We analysed data from 3,529 cases in Guinea, 5,343 in Liberia, and 10,746 in Sierra Leone; exposures were reported by 33% of cases. The proportion of cases reporting a funeral exposure decreased over time. We found a positive correlation (r = 0.35, p < 0.001) between this proportion in a given district for a given month and the within-district transmission intensity, quantified by the estimated reproduction number (R). We also found a negative correlation (r = −0.37, p < 0.001) between R and the district proportion of hospitalised cases admitted within ≤4 days of symptom onset. These two proportions were not correlated, suggesting that reduced funeral attendance and faster hospitalisation independently influenced local transmission intensity. We were able to identify 14% of potential source contacts as cases in the case line-list. Linking cases to the contacts who potentially infected them provided information on the transmission network. This revealed a high degree of heterogeneity in inferred transmissions, with only 20% of cases accounting for at least 73% of new infections, a phenomenon often called super-spreading. Multivariable regression models allowed us to identify predictors of being named as a potential source contact. These were similar for funeral and non-funeral contacts: severe symptoms, death, non-hospitalisation, older age, and travelling prior to symptom onset. Non-funeral exposures were strongly peaked around the death of the contact. There was evidence that hospitalisation reduced but did not eliminate onward exposures. We found that Ebola treatment units were better than other health care facilities at preventing exposure from hospitalised and deceased individuals. The principal limitation of our analysis is limited data quality, with cases not being entered into the database, cases not reporting exposures, or data being entered incorrectly (especially dates, and possible misclassifications). Conclusions Achieving elimination of Ebola is challenging, partly because of super-spreading. Safe funeral practices and fast hospitalisation contributed to the containment of this Ebola epidemic. Continued real-time data capture, reporting, and analysis are vital to track transmission patterns, inform resource deployment, and thus hasten and maintain elimination of the virus from the human population. PMID:27846234

The impact of the WHO Framework Convention on Tobacco Control in defending legal challenges to tobacco control measures.

PubMed

Zhou, Suzanne Y; Liberman, Jonathan D; Ricafort, Evita

2018-06-02

Since the WHO Framework Convention on Tobacco Control's (FCTC) entry into force, the tobacco industry has initiated litigation challenging tobacco control measures implemented by governments around the world, or supported others to initiate such litigation on its behalf. In defending their tobacco control measures against such litigation, governments have invoked their obligations and rights under the WHO FCTC. We assess the extent to which the WHO FCTC has provided legal weight to governments' defences against legal challenge. We reviewed 96 court decisions concerning legal challenges to tobacco control measures, determining whether or not they cited the WHO FCTC and their outcomes. We then reviewed the cases where the WHO FCTC was cited, analysing how the WHO FCTC contributed to the resolution of the case. The WHO FCTC was cited in 45 decisions. Decisions both citing and not citing the WHO FCTC were largely decided in favour of governments, with 80% of WHO-FCTC-citing and 67% of non-WHO-FCTC-citing cases upholding the measure in its entirety and on every ground of challenge. In cases where it was cited, the WHO FCTC contributed to the resolution of the case in favour of governments by providing a legal basis for measures, demonstrating the measure's public health purpose, demonstrating the evidence in favour of a measure, demonstrating international consensus, demonstrating that a measure promotes or protects health-related human rights and demonstrating whether or not a measure is reasonable, proportionate or justifiable. The way the WHO FCTC has been cited in court decisions suggests that it has made a substantial contribution to courts' reasoning in tobacco control legal challenges and has strengthened government's arguments in defending litigation. © World Health Organization 2018. Licensee BMJ Publishing Group Limited.

Cyclin D1 G870A polymorphism and breast cancer risk: a meta-analysis comprising 9,911 cases and 11,171 controls.

PubMed

Sergentanis, Theodoros N; Economopoulos, Konstantinos P

2011-11-01

Cyclin D1 represents a key molecule in the regulation of cell cycle. CCND1 G870A (rs603965) polymorphism has drawn considerable attention as the A allele may generate a variant splice product with possible oncogenic actions. A meta-analysis examining the association between CCND1 G870A polymorphism and breast cancer risk was performed. Separate analyses on Caucasian and Chinese populations were also implemented. Eligible articles were identified for the period up to July 2010. Pooled odds ratios (OR) were appropriately derived from fixed-effects or random-effects models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy-Weinberg Equilibrium (HWE) was performed. Nine case-control studies on Caucasians (7,304 cases and 8,149 controls) and four case-control studies on Chinese (2,607 cases and 3,022 controls) were eligible. At the overall analysis the A allele seemed to be associated with elevated breast cancer risk; the effect seemed to be confined to homozygous carriers (pooled OR = 1.091, 95% CI: 1.008-1.179, P = 0.030, fixed effects) as heterozygous carriers did not exhibit significantly elevated breast cancer risk. No statistically significant associations were demonstrated in Caucasians. On the other hand, Chinese AA carriers exhibited marginally elevated breast cancer risk (pooled OR = 1.144, 95% CI: 0.984-1.329, P = 0.080, fixed effects). Nevertheless, the controls in two out of the four Chinese studies deviated from HWE. In conclusion, this meta-analysis suggests that the A allele of the CCND1 G870A polymorphism may confer additional breast cancer risk when it comes to homozygosity and Chinese populations. The need for additional, methodologically sound studies on Chinese populations seems warranted.

Piecewise exponential survival times and analysis of case-cohort data.

PubMed

Li, Yan; Gail, Mitchell H; Preston, Dale L; Graubard, Barry I; Lubin, Jay H

2012-06-15

Case-cohort designs select a random sample of a cohort to be used as control with cases arising from the follow-up of the cohort. Analyses of case-cohort studies with time-varying exposures that use Cox partial likelihood methods can be computer intensive. We propose a piecewise-exponential approach where Poisson regression model parameters are estimated from a pseudolikelihood and the corresponding variances are derived by applying Taylor linearization methods that are used in survey research. The proposed approach is evaluated using Monte Carlo simulations. An illustration is provided using data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of male smokers in Finland, where a case-cohort study of serum glucose level and pancreatic cancer was analyzed. Copyright © 2012 John Wiley & Sons, Ltd.

Leucocytes telomere length and breast cancer risk/ susceptibility: A case-control study.

PubMed

Pavanello, Sofia; Varesco, Liliana; Gismondi, Viviana; Bruzzi, Paolo; Bolognesi, Claudia

2018-01-01

Telomere length in peripheral blood leukocytes (PBL-TL) was proposed as a biomarker of cancer risk. Recent scientific evidence suggested PBL-TL plays a diverse role in different cancers. Inconsistent results were obtained on PBL-TL in relation to breast cancer risk and specifically to the presence of BRCA1 and BRCA2 mutations. The aim of the present case-control study was to analyse the correlation between family history of breast cancer or presence of a BRCA mutation and PBL-TL in the hypothesis that TL is a modifier of cancer risk. PBL-TL was measured using the real-time quantitative PCR method in DNA for 142 cases and 239 controls. All the women enrolled were characterized for cancer family history. A subgroup of 48 women were classified for the presence of a BRCA mutation. PBL-TL were summarized as means and standard deviations, and compared by standard analysis of variance. A multivariable Generalised Linear Model was fitted to the data with PBL-TL as the dependent variable, case/control status and presence of a BRCA/VUS mutation as factors, and age in 4 strata as a covariate. Age was significantly associated with decreasing PBL-TL in controls (p = 0.01), but not in BC cases. The telomere length is shorter in cases than in controls after adjusting for age. No effect on PBL-TL of BMI, smoke nor of the most common risk factors for breast cancer was observed. No association between PBL-TL and family history was detected both in BC cases and controls. In the multivariate model, no association was observed between BRCA mutation and decreased PBL-TL. A statistically significant interaction (p = 0.031) between case-control status and a BRCA-mutation/VUS was observed, but no effect was detected for the interaction of cancer status and BRCA or VUS. Our study fails to provide support to the hypothesis that PBL-TL is associated with the risk of hereditary BC, or that is a marker of inherited mutations in BRCA genes.

Leucocytes telomere length and breast cancer risk/ susceptibility: A case-control study

PubMed Central

Pavanello, Sofia; Varesco, Liliana; Gismondi, Viviana; Bruzzi, Paolo

2018-01-01

Background Telomere length in peripheral blood leukocytes (PBL-TL) was proposed as a biomarker of cancer risk. Recent scientific evidence suggested PBL-TL plays a diverse role in different cancers. Inconsistent results were obtained on PBL-TL in relation to breast cancer risk and specifically to the presence of BRCA1 and BRCA2 mutations. The aim of the present case-control study was to analyse the correlation between family history of breast cancer or presence of a BRCA mutation and PBL-TL in the hypothesis that TL is a modifier of cancer risk. Methods PBL-TL was measured using the real-time quantitative PCR method in DNA for 142 cases and 239 controls. All the women enrolled were characterized for cancer family history. A subgroup of 48 women were classified for the presence of a BRCA mutation. PBL-TL were summarized as means and standard deviations, and compared by standard analysis of variance. A multivariable Generalised Linear Model was fitted to the data with PBL-TL as the dependent variable, case/control status and presence of a BRCA/VUS mutation as factors, and age in 4 strata as a covariate. Results Age was significantly associated with decreasing PBL-TL in controls (p = 0.01), but not in BC cases. The telomere length is shorter in cases than in controls after adjusting for age. No effect on PBL-TL of BMI, smoke nor of the most common risk factors for breast cancer was observed. No association between PBL-TL and family history was detected both in BC cases and controls. In the multivariate model, no association was observed between BRCA mutation and decreased PBL-TL. A statistically significant interaction (p = 0.031) between case-control status and a BRCA-mutation/VUS was observed, but no effect was detected for the interaction of cancer status and BRCA or VUS. Conclusion Our study fails to provide support to the hypothesis that PBL-TL is associated with the risk of hereditary BC, or that is a marker of inherited mutations in BRCA genes. PMID:29782524

Effects of a Web-based tailored intervention to reduce alcohol consumption in adults: randomized controlled trial.

PubMed

Schulz, Daniela N; Candel, Math Jjm; Kremers, Stef Pj; Reinwand, Dominique A; Jander, Astrid; de Vries, Hein

2013-09-17

Web-based tailored interventions provide users with information that is adapted to their individual characteristics and needs. Randomized controlled trials assessing the effects of tailored alcohol self-help programs among adults are scarce. Furthermore, it is a challenge to develop programs that can hold respondents' attention in online interventions. To assess whether a 3-session, Web-based tailored intervention is effective in reducing alcohol intake in high-risk adult drinkers and to compare 2 computer-tailoring feedback strategies (alternating vs summative) on behavioral change, dropout, and appreciation of the program. A single-blind randomized controlled trial was conducted with an experimental group and a control group (N=448) in Germany in 2010-2011. Follow-up took place after 6 months. Drinking behavior, health status, motivational determinants, and demographics were assessed among participants recruited via an online access panel. The experimental group was divided into 2 subgroups. In the alternating condition (n=132), the tailored feedback was split into a series of messages discussing individual topics offered while the respondent was filling out the program. Participants in the summative condition (n=181) received all advice at once after having answered all questions. The actual texts were identical for both conditions. The control group (n=135) only filled in 3 questionnaires. To identify intervention effects, logistic and linear regression analyses were conducted among complete cases (n=197) and after using multiple imputation. Among the complete cases (response rate: 197/448, 44.0%) who did not comply with the German national guideline for low-risk drinking at baseline, 21.1% of respondents in the experimental group complied after 6 months compared with 5.8% in the control group (effect size=0.42; OR 2.65, 95% CI 1.14-6.16, P=.02). The experimental group decreased by 3.9 drinks per week compared to 0.4 drinks per week in the control group, but this did not reach statistical significance (effect size=0.26; beta=-0.12, 95% CI -7.96 to 0.03, P=.05). Intention-to-treat analyses also indicated no statistically significant effect. Separate analyses of the 2 experimental subgroups showed no differences in intervention effects. The dropout rate during the first visit to the intervention website was significantly lower in the alternating condition than in the summative condition (OR 0.23, 95% CI 0.08-0.60, P=.003). Program appreciation was comparable for the 2 experimental groups. Complete case analyses revealed that Web-based tailored feedback can be an effective way to reduce alcohol intake among adults. However, this effect was not confirmed when applying multiple imputations. There was no indication that one of the tailoring strategies was more effective in lowering alcohol intake. Nevertheless, the lower attrition rates we found during the first visit suggest that the version of the intervention with alternating questions and advice may be preferred. International Standard Randomized Controlled Trial Number (ISRCTN): 91623132; http://www.controlled-trials.com/ISRCTN91623132 (Archived by WebCite at http://www.webcitation.org/6J4QdhXeG).

Effects of a Web-Based Tailored Intervention to Reduce Alcohol Consumption in Adults: Randomized Controlled Trial

PubMed Central

Candel, Math JJM; Kremers, Stef PJ; Reinwand, Dominique A; Jander, Astrid; de Vries, Hein

2013-01-01

Background Web-based tailored interventions provide users with information that is adapted to their individual characteristics and needs. Randomized controlled trials assessing the effects of tailored alcohol self-help programs among adults are scarce. Furthermore, it is a challenge to develop programs that can hold respondents’ attention in online interventions. Objective To assess whether a 3-session, Web-based tailored intervention is effective in reducing alcohol intake in high-risk adult drinkers and to compare 2 computer-tailoring feedback strategies (alternating vs summative) on behavioral change, dropout, and appreciation of the program. Methods A single-blind randomized controlled trial was conducted with an experimental group and a control group (N=448) in Germany in 2010-2011. Follow-up took place after 6 months. Drinking behavior, health status, motivational determinants, and demographics were assessed among participants recruited via an online access panel. The experimental group was divided into 2 subgroups. In the alternating condition (n=132), the tailored feedback was split into a series of messages discussing individual topics offered while the respondent was filling out the program. Participants in the summative condition (n=181) received all advice at once after having answered all questions. The actual texts were identical for both conditions. The control group (n=135) only filled in 3 questionnaires. To identify intervention effects, logistic and linear regression analyses were conducted among complete cases (n=197) and after using multiple imputation. Results Among the complete cases (response rate: 197/448, 44.0%) who did not comply with the German national guideline for low-risk drinking at baseline, 21.1% of respondents in the experimental group complied after 6 months compared with 5.8% in the control group (effect size=0.42; OR 2.65, 95% CI 1.14-6.16, P=.02). The experimental group decreased by 3.9 drinks per week compared to 0.4 drinks per week in the control group, but this did not reach statistical significance (effect size=0.26; beta=−0.12, 95% CI −7.96 to 0.03, P=.05). Intention-to-treat analyses also indicated no statistically significant effect. Separate analyses of the 2 experimental subgroups showed no differences in intervention effects. The dropout rate during the first visit to the intervention website was significantly lower in the alternating condition than in the summative condition (OR 0.23, 95% CI 0.08-0.60, P=.003). Program appreciation was comparable for the 2 experimental groups. Conclusions Complete case analyses revealed that Web-based tailored feedback can be an effective way to reduce alcohol intake among adults. However, this effect was not confirmed when applying multiple imputations. There was no indication that one of the tailoring strategies was more effective in lowering alcohol intake. Nevertheless, the lower attrition rates we found during the first visit suggest that the version of the intervention with alternating questions and advice may be preferred. Trial Registration International Standard Randomized Controlled Trial Number (ISRCTN): 91623132; http://www.controlled-trials.com/ISRCTN91623132 (Archived by WebCite at http://www.webcitation.org/6J4QdhXeG). PMID:24045005

TP53 mutations in squamous-cell carcinomas of the conjunctiva: evidence for UV-induced mutagenesis.

PubMed

Ateenyi-Agaba, Charles; Dai, Min; Le Calvez, Florence; Katongole-Mbidde, Edward; Smet, Anouk; Tommasino, Massimo; Franceschi, Silvia; Hainaut, Pierre; Weiderpass, Elisabete

2004-09-01

Squamous cell carcinoma of the conjunctiva is associated with sun exposure and often occurs in HIV-positive individuals. We have analysed TP53 mutations in 21 cases of squamous cell carcinoma and 22 controls with benign conjunctival lesions from a region (Uganda, Africa) with a high prevalence of heavy sun exposure and HIV infection. TP53 mutations were detected in 11 cases (52%) and 3 controls (14%). Seven of the mutations (6 in cases and 1 in controls) were CC-->TT transitions, a molecular signature of mutagenesis by solar UV rays. A similar prevalence (56%) of TP53 mutations was found in 18 squamous cell carcinoma cases positive for epidermodysplasia verruciformis human papillomavirus types. The prevalence of CC-->TT transitions reported here is the highest observed in any cancer type and matches that of skin cancers in subjects with xeroderma pigmentosum, an inherited disease with hypersensitivity to UV damage. These results confirm at the molecular level the causal role of solar UV rays in the aetiology of squamous cell carcinoma of the conjunctiva and suggest that infection with epidermodysplasia verruciformis types of human papillomavirus may act as a cofactor to increase the sensitivity of conjunctiva cells to UV-induced mutagenesis.

Baldness and testicular cancer: the EPSAM case-control study.

PubMed

Moirano, G; Zugna, D; Grasso, C; Lista, P; Ciuffreda, L; Segnan, N; Merletti, F; Richiardi, L

2016-03-01

The etiology of testicular cancer is largely unexplained. Research has mainly focused on prenatal exposures, especially to sex hormones, while less attention has been paid to exposures that may act also postnatally. As baldness has been previously associated with testicular cancer risk we focused on baldness and body hairiness, which are both associated with androgen activity. We used data of the Postnatal Exposures and Male Health (EPSAM) study, a case-control study on testicular cancer conducted in the Province of Turin, Italy, involving cases diagnosed between 1997 and 2008. Information was collected using mailed questionnaires. Analyses included 255 cases and 459 controls. We calculated ORs and 95% CIs to estimate testicular cancer risk among those who developed baldness and among those with body hairiness. We found an inverse association between testicular cancer and baldness (OR: 0.67, 95% CI: 0.46-0.98) and body hairiness (OR: 0.78, 95% CI: 0.53-1.16), although the latter had wider CIs. The inverse association between baldness and testicular cancer is consistent with the results from previous studies. These results suggest that androgens activity may influence testicular cancer risk. © 2016 American Society of Andrology and European Academy of Andrology.

A case-control study of childhood brain tumors and fathers' hobbies: a Children's Oncology Group study.

PubMed

Rosso, Andrea L; Hovinga, Mary E; Rorke-Adams, Lucy B; Spector, Logan G; Bunin, Greta R

2008-12-01

A comprehensive case-control study was conducted to evaluate parental risk factors for medulloblastoma (MB) and primitive neuroectodermal tumor (PNET). This analysis was conducted to evaluate associations between fathers' hobbies and risk of their children developing MB/PNET. The hobbies chosen for study were those with similar exposures as occupations associated with childhood cancers. Cases were 318 subjects under six years of age at diagnosis between 1991 and 1997 and registered with the Children's Cancer Group. An equal number of controls were selected through random digit dialing and individually matched to cases. In multivariate analyses, a significant association was seen for lawn care with pesticides [during pregnancy: odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.5; after birth: OR = 1.8, 95% CI: 1.2, 2.8] and a weak association was seen for stripping paint [during pregnancy: OR = 1.4, 95% CI: 0.8, 2.6; after birth: OR = 1.4, 95% CI: 0.7, 2.6]. This study suggests that household exposures from hobbies, particularly pesticides, may increase risk of MB/PNET in children; previous research has been mostly limited to occupational exposures.

A CASE-CONTROL STUDY OF CHILDHOOD BRAIN TUMORS AND FATHERS’ HOBBIES — A CHILDREN’S ONCOLOGY GROUP STUDY

PubMed Central

Rosso, Andrea L.; Hovinga, Mary E.; Rorke-Adams, Lucy B.; Spector, Logan G.; Bunin, Greta R.

2009-01-01

Objective A comprehensive case-control study was conducted to evaluate parental risk factors for medulloblastoma (MB) and primitive neuroectodermal tumor (PNET). This analysis was conducted to evaluate associations between fathers’ hobbies and risk of their children developing MB/PNET. The hobbies chosen for study were those with similar exposures as occupations associated with childhood cancers. Methods Cases were 318 subjects under 6 years of age at diagnosis between 1991-1997 and registered with the Children’s Cancer Group. An equal number of controls were selected through random digit dialing and individually matched to cases. Results In multivariate analyses, a significant association was seen for lawn care with pesticides [during pregnancy: odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.0, 2.5; after birth: OR = 1.8, 95% CI: 1.2, 2.8] and a weak association was seen for stripping paint [during pregnancy: OR = 1.4, 95% CI: 0.8, 2.6; after birth: OR = 1.4, 95% CI: 0.7, 2.6]. Conclusions This study suggests that household exposures from hobbies, particularly pesticides, may increase risk of MB/PNET in children; previous research has been mostly limited to occupational exposures. PMID:18560982

Factors associated with adult poisoning in northern Malaysia: a case-control study.

PubMed

Fathelrahman, A I; Ab Rahman, A F; Zain, Z Mohd; Tengku, M A

2006-04-01

Data on adult risk factors associated with drug or chemical poisonings in Malaysia are scarce. The objective of the study was to identify possible risk factors associated with adult admissions to the Penang General Hospital (PGH) due to chemical poisoning and/or drug overdose. The present study was a case-control study, conducted over 18 weeks. One hundred acutely poisoned adult patients admitted to PGH during the period from September 2003 to February 2004 were considered as cases. Two hundred patients admitted to the same medical wards for other illnesses, during the same period, were matched for age and gender with the poisoned cases and thus selected as controls. McNemar test and binary logistic were used for univariate analysis and logistic regression analysis for multivariate analyses. The odds ratio (OR) and its 95% confidence interval (95% CI) were calculated for each predictor variable. Positive histories of psychiatric illness and previous poisoning, problems in boy/girl friend relationships, family problems, marital problems, Indian ethnicity, Chinese ethnicity, living in rented houses and living in a household with less than five people were significant risk factors associated with adult admissions due to poisoning.

Effect of an EBM course in combination with case method learning sessions: an RCT on professional performance, job satisfaction, and self-efficacy of occupational physicians

PubMed Central

Schaafsma, Frederieke G.; Nieuwenhuijsen, Karen; van Dijk, Frank J. H.

2008-01-01

Objective An intervention existing of an evidence-based medicine (EBM) course in combination with case method learning sessions (CMLSs) was designed to enhance the professional performance, self-efficacy and job satisfaction of occupational physicians. Methods A cluster randomized controlled trial was set up and data were collected through questionnaires at baseline (T0), directly after the intervention (T1) and 7 months after baseline (T2). The data of the intervention group [T0 (n = 49), T1 (n = 31), T2 (n = 29)] and control group [T0 (n = 49), T1 (n = 28), T2 (n = 28)] were analysed in mixed model analyses. Mean scores of the perceived value of the CMLS were calculated in the intervention group. Results The overall effect of the intervention over time comparing the intervention with the control group was statistically significant for professional performance (p < 0.001). Job satisfaction and self-efficacy changes were small and not statistically significant between the groups. The perceived value of the CMLS to gain new insights and to improve the quality of their performance increased with the number of sessions followed. Conclusion An EBM course in combination with case method learning sessions is perceived as valuable and offers evidence to enhance the professional performance of occupational physicians. However, it does not seem to influence their self-efficacy and job satisfaction. PMID:18386046

Analysing policy delivery in the United Kingdom: the case of street crime and anti-social behaviour.

PubMed

Smith, Martin; Richards, David; Geddes, Andrew; Mathers, Helen

2011-01-01

For all governments, the principle of how and whether policies are implemented as intended is fundamental. The aim of this paper is to examine the difficulties for governments in delivering policy goals when they do not directly control the processes of implementation. This paper examines two case studies – anti-social behaviour and street crime – and demonstrates the difficulties faced by policy-makers in translating policy into practice when the policy problems are complex and implementation involves many actors.

Parental age and unbalanced Robertsonian translocations associated with Down syndrome and Patau syndrome: comparison with maternal and paternal age effects for 47, +21 and 47, +13.

PubMed

Hook, E B

1984-10-01

Data are analysed on livebirths with trisomic syndromes associated with unbalanced Robertsonian translocations born from 1968 to 1981 and reported to the New York State Chromosome Registry. The maternal ages of reported cases were compared with those of the livebirths in the general population who were born in the same year. The number of translocations studied, the mean case-control differences in years in maternal age (and the standard errors of the mean) were respectively, as follows: D/21 mutants, n = 36, -0.1 (+/- 0.9); G/21 mutants, n = 46, +1.5 (+/-0.8); D/13 mutants, n = 16, +0.6 (+/-1.5); D/21 inherited, n = 12, -1.0 (+/-1.4); G/21 inherited, n = 3, -0.3 (+/-4.4); and D/13 inherited, n = 6, +2.1 (+/-2.4). There was little change in any category if the few cases diagnosed prenatally were included. Only the value for the G/21 mutants is significantly different from zero at the 0.05 level. (The results on G/21 mutants in maternal age are consistent with an earlier Japanese report of an increase of about 2 years over the control values.) The distribution of maternal ages suggests that G/21 mutants may be produced both by maternal age-independent and maternal age-dependent components. The data on D/21 mutants, however, do not indicate the negative association with maternal age reported in Japan. Differences between this study and the Japanese study in analyses of controls may explain this slight variation. But in any event both studies reveal no evidence for an increase in maternal age for unbalanced D/21 mutant or D/21 inherited translocations associated with Down syndrome. This is evidence against the hypothesis that relaxed selection during gestation, after recognition of pregnancy, accounts for the maternal age effects of 47, +21. In comparison with the results on Robertsonian translocations, the case-control differences in maternal age in years (and the standard errors of the mean) for 47, +21 for 2148 livebirths was +4.6 (+/-0.2), and for 2354 cases including those diagnosed prenatally was +5.3 (+/-0.2). The most likely value for an estimated total of 2292 cases of 47, +21 livebirths that would have been reported in the absence of prenatal diagnosis was +5.1 (+/-0.2). For 47, +13, for 98 livebirths the mean case-control difference in maternal age in years was +1.5 (+/-0.7) and for 116 cases including those diagnosed prenatally was +3.2 (+/-0.7).(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of Hospital Closures on Acute Care Outcomes in British Columbia, Canada: An Interrupted Time Series Study.

PubMed

Panagiotoglou, Dimitra; Law, Michael R; McGrail, Kimberlyn

2017-01-01

In 2002 British Columbia, Canada began redistributing its hospital services. We used administrative data and interrupted time series analyses to determine how recent hospital closures affected patient outcomes. All adult acute myocardial infarction (AMI), stroke, and trauma events in British Columbia between fiscal years 1999 and 2013. Cases were patients whose closest hospital closed. Controls were matched by condition, year of event, and condition-specific hospital volume where treatment was received. Thirty-day mortality and hospital bypass rates. We matched 3267 AMI, 2852 stroke, and 6318 trauma cases to 1996, 1604, and 3640 controls, respectively. The 30-day mortality rate at baseline was 7.0% [95% confidence interval (CI), 4.0%-10.1%] for AMI, 5.3% (95% CI, 2.4%-8.1%) for stroke, and 1.2% (95% CI, 0.3%-2.1%) for trauma controls. The 30-day mortality rate for cases was 14.3% (95% CI, 7.1%-21.7%) for AMI, 12.0% (95% CI, 5.1%-18.9%) for stroke, and 3.1% for trauma (95% CI, 0.9%-5.2%) cases. There was no significant change in 30-day mortality for cases, and no significant difference in change in mortality rates between cases and controls following the intervention. The difference in hospital bypass rates between cases and controls was 50.1% (95% CI, 42.3%-57.9%) for AMI, 36.2% (95% CI, 27.4%-44.9%) for stroke, and 32.2% (95% CI, 27.7%-36.8%) for trauma cases preintervention. Following the intervention, the difference in bypass rates dropped by 15.5% (95% CI, 3.5%-27.5%) for AMI, 25.3% (95% CI, 11.7%-38.8%) for stroke, and 22.7% (95% CI, 15.7%-29.6%) for trauma cases. Hospital closures did not affect patient mortality.

Case definition terminology for paratuberculosis (Johne's disease).

PubMed

Whittington, R J; Begg, D J; de Silva, K; Purdie, A C; Dhand, N K; Plain, K M

2017-11-09

Paratuberculosis (Johne's disease) is an economically significant condition caused by Mycobacterium avium subsp. paratuberculosis. However, difficulties in diagnosis and classification of individual animals with the condition have hampered research and impeded efforts to halt its progressive spread in the global livestock industry. Descriptive terms applied to individual animals and herds such as exposed, infected, diseased, clinical, sub-clinical, infectious and resistant need to be defined so that they can be incorporated consistently into well-understood and reproducible case definitions. These allow for consistent classification of individuals in a population for the purposes of analysis based on accurate counts. The outputs might include the incidence of cases, frequency distributions of the number of cases by age class or more sophisticated analyses involving statistical comparisons of immune responses in vaccine development studies, or gene frequencies or expression data from cases and controls in genomic investigations. It is necessary to have agreed definitions in order to be able to make valid comparisons and meta-analyses of experiments conducted over time by a given researcher, in different laboratories, by different researchers, and in different countries. In this paper, terms are applied systematically in an hierarchical flow chart to enable classification of individual animals. We propose descriptive terms for different stages in the pathogenesis of paratuberculosis to enable their use in different types of studies and to enable an independent assessment of the extent to which accepted definitions for stages of disease have been applied consistently in any given study. This will assist in the general interpretation of data between studies, and will facilitate future meta-analyses.

Chronic periodontitis is associated with erectile dysfunction. A case-control study in european population.

PubMed

Martín, Amada; Bravo, Manuel; Arrabal, Miguel; Magán-Fernández, Antonio; Mesa, Francisco

2018-07-01

To determine the association between chronic periodontitis and erectile dysfunction adjusting for biochemical markers and other comorbidities. A case-control study was conducted on 158 male patients; 80 cases with erectile dysfunction according to the International Index of Erectile Function and 78 controls. Sociodemographic data were gathered, and a periodontal examination was performed. Testosterone, lipid profile, C-reactive protein and glycaemic parameters were assessed. All variables were compared between groups, and multivariate logistic regression analyses were performed. 74% of the cases were diagnosed with chronic periodontitis. Number of sites with pocket probing depth 4-6 mm (p = 0.05) and number of sites with clinical attachment loss >3 mm (p < 0.01) were higher in the cases. Triglycerides (p < 0.01), C-reactive protein (p = 0.02) and glycosylated haemoglobin (p = 0.04) were also higher in the cases. Logistic regression showed that patients with chronic periodontitis were more likely to have erectile dysfunction (OR=2.17; 95% CI (1.06-4.43); p = 0.03) independently of other confounders. Patients with erectile dysfunction showed worse periodontal condition. Chronic periodontitis seems to play a key role as a risk factor in the pathogenesis of erectile dysfunction independently of other morbidities. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Measurement of cerebral biomarkers proving traumatic brain injuries in post-mortem body fluids.

PubMed

Ondruschka, Benjamin; Sieber, Monique; Kirsten, Holger; Franke, Heike; Dressler, Jan

2018-05-05

Until now, it is impossible to identify a fatal traumatic brain injury (TBI) before post-mortem radiological investigations or an autopsy take place. It would be preferable to have an additional diagnostic tool like post-mortem biochemistry to get greater insight into the pathological pathways and survival times after sustaining TBI. Cerebrospinal fluid (CSF) and serum samples of 84 autopsy cases were collected from forensic autopsies with post-mortem intervals (PMI) of up to 148 h. The cases were categorized into a fatal TBI case group (n=42) and non-TBI controls (n=42). The values of glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and neutrophil gelatinase-associated lipocalin (NGAL) were analyzed by means of quantitative chemiluminescent multiplex immunoassays. The main results indicate that the usage of liquid samples with good macroscopic quality is more relevant for meaningful biomarker analyses than the length of the PMI. All three proteins were shown to differentiate TBI fatalities from the controls in CSF. In serum, only GFAP could be shown to be able to identify TBI cases. This study is the first approach to measure the three proteins together in CSF and serum in autopsy cases. Determined threshold values may differentiate between fatal TBI and control cases. The presented results emphasize the possible use of post-mortem biochemistry as a supplemental tool in everyday forensic routine.

Economic Effects of Introducing Alternative Salmonella Control Strategies in Sweden

PubMed Central

Sundström, Kristian; Wahlström, Helene; Ivarsson, Sofie; Sternberg Lewerin, Susanna

2014-01-01

The objective of the study was to analyse the economic effects of introducing alternative Salmonella control strategies in Sweden. Current control strategies in Denmark and the Netherlands were used as benchmarks. The true number of human Salmonella cases was estimated by reconstructing the reporting pyramids for the various scenarios. Costs were calculated for expected changes in human morbidity (Salmonella and two of its sequelae), for differences in the control programmes and for changes in cattle morbidity. The net effects (benefits minus costs) were negative in all scenarios (€ −5 to −105 million), implying that it would not be cost-effective to introduce alternative control strategies in Sweden. This result was mainly due to an expected increase in the incidence of Salmonella in humans (6035–57108 reported and unreported new cases/year), with expected additional costs of € 5–55 million. Other increased costs were due to expected higher incidences of sequelae (€ 3–49 million) and a higher cattle morbidity (€ 4–8 million). Benefits in terms of lower control costs amounted to € 4–7 million. PMID:24831797

The role of Leptospira spp. in horses affected with recurrent uveitis in the UK.

PubMed

Malalana, F; Blundell, R J; Pinchbeck, G L; Mcgowan, C M

2017-11-01

Equine recurrent uveitis (ERU) is a common cause of ocular pain and blindness in horses. Leptospira spp. have been commonly implicated in the pathophysiology of ERU in mainland Europe and the USA. No recent studies have been carried out in the UK, but Leptospira is reported not to be a major factor in the aetiology of ERU in the UK. To establish the prevalence of Leptospira-associated ERU in the UK and to identify the serovars involved in these cases; to compare serum vs. aqueous humour antibody levels in cases and controls in order to confirm the diagnosis of Leptospira-associated ERU, and to assess the usefulness of serology alone as a confirmatory test for Leptospira-associated ERU in the UK. Case-control study. Eyes enucleated for clinical reasons in ERU-affected horses were collected. Blood and aqueous humour were obtained to determine antibody levels against a variety of Leptospira serovars and C-values (aqueous humour value/serum value) were calculated. In addition, eyes, blood and aqueous humour were obtained from control cases for comparison. Histopathology was performed in all eyes to confirm uveitis in each case. Differences in seroprevalences between ERU and control cases and between Leptospira- and non-Leptospira-associated ERU cases were calculated. A total of 30 ERU and 43 control eyes were analysed. Of the ERU eyes, only two had a C-value of >4 (prevalence of Leptospira-associated uveitis: 6.7%). Serovars hardjo and javanica were detected. There was no difference in seroprevalence between horses with uveitis and control cases (65.5% and 41.9%, respectively; P = 0.11) or between Leptospira- and non-Leptospira-associated uveitis cases (100% and 63.0%, respectively; P = 0.52). The study was limited by low case numbers. Eyes were presented at different stages of disease. The only test used to detect Leptospira was the microscopic agglutination test. Leptospira-associated ERU is uncommon in the UK. Serology alone may not help to definitively diagnose Leptospira-associated uveitis in this country. © 2017 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.

Is there any interaction between domestic radon exposure and air pollution from traffic in relation to childhood leukemia risk?

PubMed

Bräuner, Elvira Vaclavik; Andersen, Claus E; Andersen, Helle P; Gravesen, Peter; Lind, Morten; Ulbak, Kaare; Hertel, Ole; Schüz, Joachim; Raaschou-Nielsen, Ole

2010-11-01

In a recent population-based case-control study using 2,400 cases of childhood cancer, we found a statistically significant association between residential radon and acute lymphoblastic leukemia risk. Traffic exhaust in the air enhances the risk association between radon and childhood leukemia. We included 985 cases of childhood leukemia and 1,969 control children. We used validated models to calculate residential radon and street NO(x) concentrations for each home. Conditional logistic regression analyses were used to analyze the effect of radon on childhood leukemia risk within different strata of air pollution and traffic density. The relative risk for childhood leukemia in association with a 10(3) Bq/m(3)-years increase in radon was 1.77 (1.11, 2.82) among those exposed to high levels of NO(x) and 1.23 (0.79, 1.91) for those exposed to low levels of NO(x) (p(interaction,) 0.17). Analyses for different morphological subtypes of leukemia and within different strata of traffic density showed a non-significant pattern of stronger associations between radon and childhood leukemia within strata of higher traffic density at the street address. Air pollution from traffic may enhance the effect of radon on the risk of childhood leukemia. The observed tendency may also be attributed to chance.

Endotoxin exposure and lung cancer risk: a systematic review and meta-analysis of the published literature on agriculture and cotton textile workers.

PubMed

Lenters, Virissa; Basinas, Ioannis; Beane-Freeman, Laura; Boffetta, Paolo; Checkoway, Harvey; Coggon, David; Portengen, Lützen; Sim, Malcolm; Wouters, Inge M; Heederik, Dick; Vermeulen, Roel

2010-04-01

To examine the association between exposure to endotoxins and lung cancer risk by conducting a systematic review and meta-analysis of epidemiologic studies of workers in the cotton textile and agricultural industries; industries known for high exposure levels of endotoxins. Risk estimates were extracted from studies published before 2009 that met predefined quality criteria, including 8 cohort, 1 case-cohort, and 2 case-control studies of cotton textile industry workers, and 15 cohort and 2 case-control studies of agricultural workers. Summary risk estimates were calculated using random effects meta-analyses. Potential sources of heterogeneity were explored through subgroup analyses. The summary risk of lung cancer was 0.72 (95% CI, 0.57-0.90) for textile workers and 0.62 (0.52-0.75) for agricultural workers. The relative risk of lung cancer was below 1.0 for most subgroups defined according to sex, study design, outcome, smoking adjustment, and geographic area. Two studies provided quantitative estimates of endotoxin exposure and both studies tended to support a dose-dependent protective effect of endotoxins on lung cancer risk. Despite several limitations, this meta-analysis based on high-quality studies adds weight to the hypothesis that occupational exposure to endotoxin in cotton textile production and agriculture is protective against lung cancer.

Tularaemia outbreaks in Sakarya, Turkey: case-control and environmental studies.

PubMed

Meric, M; Sayan, M; Dundar, D; Willke, A

2010-08-01

Tularaemia is an important zoonotic disease that leads to outbreaks. This study aimed to compare the epidemiological characteristics of two tularaemia outbreaks that occurred in the Sakarya region of Turkey, analyse the risk factors for the development of outbreaks and identify Francisella (F.) tularensis in the water samples. Two tularaemia outbreaks occurred in the Kocadongel village in 2005 and 2006. A field investigation and a case-control study with 47 cases and 47 healthy households were performed during the second outbreak. Clinical samples from the patients and filtrated water samples were analysed for F. tularensis via real-time polymerase chain reaction. From the two outbreaks, a total of 58 patients were diagnosed with oropharyngeal tularaemia based on their clinical and serological results. Both outbreaks occurred between the months of January and April, and the number of patients peaked in February. Logistic regression analysis revealed that the consumption of natural spring water was the only significant risk factor for tularaemia infection (odds ratio 3.5, confidence interval 1.23-10.07). F. tularensis was detected in eight clinical samples and in the filtrated natural spring water. This study is the first report of tularaemia from this region. The results show that both tularaemia outbreaks were related to the consumption of untreated natural spring water. To prevent waterborne tularaemia, community water supplies should be treated and checked periodically.

Relationship between cataract severity and socioeconomic status.

PubMed

Wesolosky, Jason D; Rudnisky, Christopher J

2013-12-01

To determine the relationship between cataract severity and socioeconomic status (SES). Retrospective, observational case series. A total of 1350 eyes underwent phacoemulsification cataract extraction by a single surgeon using an Alcon Infiniti system. Cataract severity was measured using phaco time in seconds. SES was measured using area-level aggregate census data: median income, education, proportion of common-law couples, and employment rate. Preoperative best corrected visual acuity was obtained and converted to logarithm of the minimum angle of resolution values. For patients undergoing bilateral surgery, the generalized estimating equation was used to account for the correlation between eyes. Univariate analyses were performed using simple regression, and multivariate analyses were performed to account for variables with significant relationships (p < 0.05) on univariate testing. Sensitivity analyses were performed to assess the effect of including patient age in the controlled analyses. Multivariate analyses demonstrated that cataracts were more severe when the median income was lower (p = 0.001) and the proportion of common-law couples living in a patient's community (p = 0.012) and the unemployment rate (p = 0.002) were higher. These associations persisted even when controlling for patient age. Patients of lower SES have more severe cataracts. Copyright © 2013 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Association between global DNA hypomethylation in leukocytes and risk of breast cancer

PubMed Central

Choi, Ji-Yeob; James, Smitha R.; Link, Petra A.; McCann, Susan E.; Hong, Chi-Chen; Davis, Warren; Nesline, Mary K.; Ambrosone, Christine B.; Karpf, Adam R.

2009-01-01

Background: Global DNA hypomethylation may result in chromosomal instability and oncogene activation, and as a surrogate of systemic methylation activity, may be associated with breast cancer risk. Methods: Samples and data were obtained from women with incident early-stage breast cancer (I–IIIa) and women who were cancer free, frequency matched on age and race. In preliminary analyses, genomic methylation of leukocyte DNA was determined by measuring 5-methyldeoxycytosine (5-mdC), as well as methylation analysis of the LINE-1-repetitive DNA element. Further analyses used only 5-mdC levels. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of breast cancer in relation to amounts of methylation. Results: In a subset of samples tested (n = 37), 5-mdC level was not correlated with LINE-1 methylation. 5-mdC level in leukocyte DNA was significantly lower in breast cancer cases than healthy controls (P = 0.001), but no significant case–control differences were observed with LINE-1 methylation (P = 0.176). In the entire data set, we noted significant differences in 5-mdC levels in leukocytes between cases (n = 176) and controls (n = 173); P value < 0.001. Compared with women in the highest 5-mdC tertile (T3), women in the second (T2; OR = 1.49, 95% CI = 0.84–2.65) and lowest tertile (T1; OR = 2.86, 95% CI = 1.65–4.94) had higher risk of breast cancer (P for trend ≤0.001). Among controls only and cases and controls combined, only alcohol intake was found to be inversely associated with methylation levels. Conclusion: These findings suggest that leukocyte DNA hypomethylation is independently associated with development of breast cancer. PMID:19584139

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

FOXP3 gene variations and susceptibility to autism: A case-control study.

PubMed

Safari, Mohammad Reza; Ghafouri-Fard, Soudeh; Noroozi, Rezvan; Sayad, Arezou; Omrani, Mir Davood; Komaki, Alireza; Eftekharian, Mohammad Mahdi; Taheri, Mohammad

2017-01-05

Autism Spectrum Disorders (ASD) are a group of heterogeneous neurodevelopmental disorders associated with immune system dysregulation. There are supporting evidences for the role of Forkhead Box P3 (FOXP3) gene as a lineage specification factor of regulatory T cells in the pathogenesis of ASD. The aim of this study was to explore possible relationship between genetic variants rs2232365 and rs3761548 of FOXP3 and ASD in 523 ASD patients versus 472 control individuals. Allele frequency analyses showed significant overpresentation of rs2232365-G allele in cases versus controls. In addition, rs2232365 GG genotype was associated with ASD in dominant inheritance model. Haplotype analysis revealed no significant association of any estimated block of rs2232365/rs3761548 with ASD. Our study indicated that rs2232365 is associated with ASD. Copyright © 2016 Elsevier B.V. All rights reserved.

Defining a reference set to support methodological research in drug safety.

PubMed

Ryan, Patrick B; Schuemie, Martijn J; Welebob, Emily; Duke, Jon; Valentine, Sarah; Hartzema, Abraham G

2013-10-01

Methodological research to evaluate the performance of methods requires a benchmark to serve as a referent comparison. In drug safety, the performance of analyses of spontaneous adverse event reporting databases and observational healthcare data, such as administrative claims and electronic health records, has been limited by the lack of such standards. To establish a reference set of test cases that contain both positive and negative controls, which can serve the basis for methodological research in evaluating methods performance in identifying drug safety issues. Systematic literature review and natural language processing of structured product labeling was performed to identify evidence to support the classification of drugs as either positive controls or negative controls for four outcomes: acute liver injury, acute kidney injury, acute myocardial infarction, and upper gastrointestinal bleeding. Three-hundred and ninety-nine test cases comprised of 165 positive controls and 234 negative controls were identified across the four outcomes. The majority of positive controls for acute kidney injury and upper gastrointestinal bleeding were supported by randomized clinical trial evidence, while the majority of positive controls for acute liver injury and acute myocardial infarction were only supported based on published case reports. Literature estimates for the positive controls shows substantial variability that limits the ability to establish a reference set with known effect sizes. A reference set of test cases can be established to facilitate methodological research in drug safety. Creating a sufficient sample of drug-outcome pairs with binary classification of having no effect (negative controls) or having an increased effect (positive controls) is possible and can enable estimation of predictive accuracy through discrimination. Since the magnitude of the positive effects cannot be reliably obtained and the quality of evidence may vary across outcomes, assumptions are required to use the test cases in real data for purposes of measuring bias, mean squared error, or coverage probability.

Conditional Poisson models: a flexible alternative to conditional logistic case cross-over analysis.

PubMed

Armstrong, Ben G; Gasparrini, Antonio; Tobias, Aurelio

2014-11-24

The time stratified case cross-over approach is a popular alternative to conventional time series regression for analysing associations between time series of environmental exposures (air pollution, weather) and counts of health outcomes. These are almost always analyzed using conditional logistic regression on data expanded to case-control (case crossover) format, but this has some limitations. In particular adjusting for overdispersion and auto-correlation in the counts is not possible. It has been established that a Poisson model for counts with stratum indicators gives identical estimates to those from conditional logistic regression and does not have these limitations, but it is little used, probably because of the overheads in estimating many stratum parameters. The conditional Poisson model avoids estimating stratum parameters by conditioning on the total event count in each stratum, thus simplifying the computing and increasing the number of strata for which fitting is feasible compared with the standard unconditional Poisson model. Unlike the conditional logistic model, the conditional Poisson model does not require expanding the data, and can adjust for overdispersion and auto-correlation. It is available in Stata, R, and other packages. By applying to some real data and using simulations, we demonstrate that conditional Poisson models were simpler to code and shorter to run than are conditional logistic analyses and can be fitted to larger data sets than possible with standard Poisson models. Allowing for overdispersion or autocorrelation was possible with the conditional Poisson model but when not required this model gave identical estimates to those from conditional logistic regression. Conditional Poisson regression models provide an alternative to case crossover analysis of stratified time series data with some advantages. The conditional Poisson model can also be used in other contexts in which primary control for confounding is by fine stratification.

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).

Risk of Peripheral Artery Occlusive Disease in Patients with Vertigo, Tinnitus, or Sudden Deafness: A Secondary Case-Control Analysis of a Nationwide, Population-Based Health Claims Database.

PubMed

Koo, Malcolm; Chen, Jin-Cherng; Hwang, Juen-Haur

2016-01-01

Cochleovestibular symptoms, such as vertigo, tinnitus, and sudden deafness, are common manifestations of microvascular diseases. However, it is unclear whether these symptoms occurred preceding the diagnosis of peripheral artery occlusive disease (PAOD). Therefore, the aim of this case-control study was to investigate the risk of PAOD among patients with vertigo, tinnitus, and sudden deafness using a nationwide, population-based health claim database in Taiwan. We identified 5,340 adult patients with PAOD diagnosed between January 1, 2006 and December 31, 2010 and 16,020 controls, frequency matched on age interval, sex, and year of index date, from the Taiwan National Health Insurance Research Database. Risks of PAOD in patients with vertigo, tinnitus, or sudden deafness were separately evaluated with multivariate logistic regression analyses. Of the 5,340 patients with PAOD, 12.7%, 6.7%, and 0.3% were diagnosed with vertigo, tinnitus, and sudden deafness, respectively. In the controls, 10.6%, 6.1%, and 0.3% were diagnosed with vertigo (P < 0.001), tinnitus (P = 0.161), and sudden deafness (P = 0.774), respectively. Results from the multivariate logistic regression analyses showed that the risk of PAOD was significantly increased in patients with vertigo (adjusted odds ratio = 1.12, P = 0.027) but not in those with tinnitus or sudden deafness. A modest increase in the risk of PAOD was observed among Taiwanese patients with vertigo, after adjustment for comorbidities.

Risk factors associated with sporadic salmonellosis in adults: a case-control study.

PubMed

Ziehm, D; Dreesman, J; Campe, A; Kreienbrock, L; Pulz, M

2013-02-01

In order to identify and assess recent risk factors for sporadic human infections with Salmonella enterica, we conducted a case-control study in Lower Saxony, Germany. The data collection was based on standardized telephone interviews with 1017 cases and 346 controls aged >14 years. Odds ratios were calculated in single-factor and multi-factor analyses for Salmonella cases and two different control groups, i.e. population controls and controls with rotavirus infection. Multi-factor analysis revealed associations between sporadic Salmonella infections for two exposures by both sets of controls: consumption of raw ground pork [adjusted odds ratio (aOR) 2·38, 95% confidence interval (CI) 1·27-4·44] and foreign travel (aOR 2·12, 95% CI 1·00-4·52). Other exposures included consumption of food items containing eggs (aOR 1·43, 95% CI 0·80-2·54), consumption of chicken meat (aOR 1·77, 95% CI 1·26-2·50), outdoor meals/barbecues (aOR 3·96, 95% CI 1·41-11·12) and taking gastric acidity inhibitors (aOR 2·42, 95% CI 1·19-4·92), all were significantly associated with respect to one of the two control groups. The impact of consuming food items containing eggs or chicken meat was lower than expected from the literature. This might be a consequence of Salmonella control programmes as well as increased public awareness of eggs and chicken products being a risk factor for salmonellosis. Efforts to reduce Salmonella infections due to raw pork products should be intensified.

A case control study of association between cognition and functional capacity in schizophrenia.

PubMed

Narayanan, Sreelatha S; Bhatia, Triptish; Velligan, Dawn I; Nimgaonkar, Vishwajit L; Deshpande, Smita N

2015-12-01

Cognitive functions are important prognostic factors for schizophrenia (SZ), while ability to perform activities of daily living are important measures of functional capacity. The relationship between cognition and functional capacity has not been tested extensively in India. To compare persons with SZ with controls on measures of cognition and functional capacity, and evaluate correlations between cognitive performance and functional capacity. Schizophrenia outpatients and controls without psychiatric illness (DSM IV) who completed the MATRICS Consensus Cognitive Battery and Functional Assessment Battery comprised of two tests from University of California San Diego (UCSD) Performance Based Skill Assessment (UPSA), one Test of Adaptive Behavior in Schizophrenia (TABS) and one test from University of California San Diego Performance Based Skill Assessment Brief edition (UPSA-B). Cognitive and functional domains were examined using regression analyses, with relevant covariates. Cases (N=51) though younger, were more educated than controls (N=41). Adjusting for education, controls performed better than cases in 3/7 cognitive and 4/5 domains of functional capacity but similarly in 'household management'. Among both cases and controls, cognitive measures of verbal learning and speed of processing overlapped with functional capacity (3 domains). Working memory was associated with one functional domain. Consistent with other studies, Indian patients with schizophrenia performed worse than controls on several domains of cognition and functional capacity; these domains were correlated. Speed of processing and verbal learning are most frequently associated with functional capacity indices and should be targeted to improve skills of daily living among persons with SZ. Copyright © 2015. Published by Elsevier B.V.

Determinants of first trimester attendance at antenatal care clinics in the Amazon region of Peru: A case-control study

PubMed Central

Moore, Nora; Blouin, Brittany; Razuri, Hugo; Casapia, Martin; Gyorkos, Theresa W.

2017-01-01

Objective To identify determinants which influence the timing of the first antenatal care (ANC) visit in pregnant women. Design Retrospective matched nested case-control study. Setting Two health centres, Belén and 6 de Octubre, in the Peruvian Amazon. Population All pregnant women who had attended ANC during the years 2010, 2011, and 2012. Methods All cases (819 women initiating ANC in their first trimester) were selected from ANC registries from 2010 to 2012. A random sample of controls (819 women initiating ANC in their second or third trimester) was matched 1:1 to cases on health centre and date of first ANC visit. Data were obtained from ANC registries. Conditional logistic regression analyses were performed. Main outcome measure Case-control status of each woman determined by the gestational age at first ANC visit. Results Cases had higher odds of: 1) being married or cohabiting (aOR = 1.69; 95% CI: 1.19, 2.41); 2) completing secondary school or attending post-secondary school (aOR = 1.45; 95% CI: 1.02, 2.06); 3) living in an urban environment (aOR = 1.79; 95% CI: 1.04, 3.10) and 4) having had a previous miscarriage (aOR = 1.56; 95% CI: 1.13, 2.15), compared to controls. No statistically significant difference in odds was found for parity (aOR = 1.08; 95% CI: 0.85, 1.36). Conclusions This study provides empirical evidence of determinants of first ANC attendance. These findings are crucial to the planning and timing of local interventions, like deworming, aimed at pregnant women so that they can access and benefit fully from all government-provided ANC services. PMID:28207749

Determinants of first trimester attendance at antenatal care clinics in the Amazon region of Peru: A case-control study.

PubMed

Moore, Nora; Blouin, Brittany; Razuri, Hugo; Casapia, Martin; Gyorkos, Theresa W

2017-01-01

To identify determinants which influence the timing of the first antenatal care (ANC) visit in pregnant women. Retrospective matched nested case-control study. Two health centres, Belén and 6 de Octubre, in the Peruvian Amazon. All pregnant women who had attended ANC during the years 2010, 2011, and 2012. All cases (819 women initiating ANC in their first trimester) were selected from ANC registries from 2010 to 2012. A random sample of controls (819 women initiating ANC in their second or third trimester) was matched 1:1 to cases on health centre and date of first ANC visit. Data were obtained from ANC registries. Conditional logistic regression analyses were performed. Case-control status of each woman determined by the gestational age at first ANC visit. Cases had higher odds of: 1) being married or cohabiting (aOR = 1.69; 95% CI: 1.19, 2.41); 2) completing secondary school or attending post-secondary school (aOR = 1.45; 95% CI: 1.02, 2.06); 3) living in an urban environment (aOR = 1.79; 95% CI: 1.04, 3.10) and 4) having had a previous miscarriage (aOR = 1.56; 95% CI: 1.13, 2.15), compared to controls. No statistically significant difference in odds was found for parity (aOR = 1.08; 95% CI: 0.85, 1.36). This study provides empirical evidence of determinants of first ANC attendance. These findings are crucial to the planning and timing of local interventions, like deworming, aimed at pregnant women so that they can access and benefit fully from all government-provided ANC services.

Air pollution and childhood leukaemia: a nationwide case-control study in Italy.

PubMed

Badaloni, C; Ranucci, A; Cesaroni, G; Zanini, G; Vienneau, D; Al-Aidrous, F; De Hoogh, K; Magnani, C; Forastiere, F

2013-12-01

Leukaemia is the most common cancer in children, but its aetiology is still poorly understood. We tested the hypothesis that traffic-related air pollution is associated with paediatric leukaemia because of chronic exposure to several potential carcinogens. The Italian SETIL study (Study on the aetiology of lymphohematopoietic malignancies in children) was conducted in 14 Italian regions. All incident cases of leukaemia in children aged ≤10 years from these regions (period 1998-2001) were eligible for enrolment. Two controls per case, matched on birth date, gender and region of residence were randomly selected from the local population registries. Exposure assessment at birth residence included traffic indicators (distance to main roads and length of main roads within 100 m) and estimates of pollutants concentrations (particulate matter -PM2.5 and PM10- and gases -NO2 and O3-) from national dispersion model and land use regression models. The association between the exposure variables and leukaemia was assessed by logistic regression analyses. Participation rates were 91.4% among cases and 69.2% in controls; 620 cases (544 acute lymphocytic and 76 acute non-lymphocytic leukaemia) and 957 controls were included. Overall, when considering the residence at birth, 35.6% of cases and 42.4% of controls lived along busy roads, and the mean annual PM10 levels were 33.3 (SD=6.3) and 33.4 µg/m(3) (SD=6.5), respectively. No association was found, and all ORs, independent of the method of assessment and the exposure windows, were close to the null value. Using various exposure assessment strategies, air pollution appears not to affect the incidence of childhood leukaemia.

Trouble with bleeding: risk factors for acute hepatitis C among HIV-positive gay men from Germany--a case-control study.

PubMed

Schmidt, Axel J; Rockstroh, Jürgen K; Vogel, Martin; An der Heiden, Matthias; Baillot, Armin; Krznaric, Ivanka; Radun, Doris

2011-03-08

To identify risk factors for hepatitis C among HIV-positive men who have sex with men (MSM), focusing on potential sexual, nosocomial, and other non-sexual determinants. Outbreaks of hepatitis C virus (HCV) infections among HIV-positive MSM have been reported by clinicians in post-industrialized countries since 2000. The sexual acquisition of HCV by gay men who are HIV positive is not, however, fully understood. Between 2006 and 2008, a case-control study was embedded into a behavioural survey of MSM in Germany. Cases were HIV-positive and acutely HCV-co-infected, with no history of injection drug use. HIV-positive MSM without known HCV infection, matched for age group, served as controls. The HCV-serostatus of controls was assessed by serological testing of dried blood specimens. Univariable and multivariable regression analyses were used to identify factors independently associated with HCV-co-infection. 34 cases and 67 controls were included. Sex-associated rectal bleeding, receptive fisting and snorting cocaine/amphetamines, combined with group sex, were independently associated with case status. Among cases, surgical interventions overlapped with sex-associated rectal bleeding. Sexual practices leading to rectal bleeding, and snorting drugs in settings of increased HCV-prevalence are risk factors for acute hepatitis C. We suggest that sharing snorting equipment as well as sharing sexual partners might be modes of sexual transmission. Condoms and gloves may not provide adequate protection if they are contaminated with blood. Public health interventions for HIV-positive gay men should address the role of blood in sexual risk behaviour. Further research is needed into the interplay of proctosurgery and sex-associated rectal bleeding.

Maternal occupational exposure during pregnancy and the risk of spina bifida.

PubMed Central

Blatter, B M; Roeleveld, N; Zielhuis, G A; Gabreëls, F J; Verbeek, A L

1996-01-01

OBJECTIVES: A case-control study was carried out to explore associations between spina bifida and occupational exposure of the mother. METHODS: The cases were children with spina bifida aperta born between 1980 and 1992 from nine hospitals in the Netherlands. The controls were children born healthy in the same period as the cases, from hospitals and from the general population. Data collection was carried out in two steps. Firstly, postal questionnaires were sent to all the parents of cases and controls to gather information on occupations and potential confounders. In the second phase of the study, information on specific exposures was collected by means of job and task specific personal interviews. Interviews were performed with 55 case mothers and 66 control mothers who had occupations with a potential for chemical or physical exposure. Those exposures were assumed to be negligible for--for example, teachers and secretaries, so personal interviews were not indicated for these women. Information was collected on specific tasks in the period just after conception, and on the associated use of chemical or physical agents, frequency of exposure, and use of protective equipment. RESULTS: The analyses of occupation showed an increased risk for women working in agricultural occupations (OR = 3.4, CI:1.3-9.0), and, although less distinct, for cleaning women (OR = 1.7, CI:0.9-3.4). Only a few women seemed to be occupationally exposed to chemical or physical agents. No differences in occurrence of specific exposures could be detected between cases and controls. Besides, no differences were seen in pesticide or disinfectant exposure among case and control mothers in agricultural occupations. CONCLUSIONS: Occupational exposures of the mother during pregnancy were infrequent and did not seem to play an important part in the aetiology of spina bifida in this study. The association found between spina bifida and maternal agricultural occupations could not be explained by the use of pesticides by the mother or by any other occupational exposure. PMID:8777455

Pelvic Actinomycosis

PubMed Central

García-García, Alejandra; Ramírez-Durán, Ninfa; Sandoval-Trujillo, Horacio

2017-01-01

Introduction Actinomycosis is a chronic bacterial infection caused by Actinomyces, Gram-positive anaerobic bacteria. Its symptomatology imitates some malignant pelvic tumours, tuberculosis, or nocardiosis, causing abscesses and fistulas. Actinomycoses are opportunistic infections and require normal mucous barriers to be altered. No epidemiological studies have been conducted to determine prevalence or incidence of such infections. Objective To analyse the clinical cases of pelvic actinomycosis reported worldwide, to update the information about the disease. Methods A systematic review of worldwide pelvic actinomycosis cases between 1980 and 2014 was performed, utilising the PubMed, Scopus, and Google Scholar databases. The following information was analysed: year, country, type of study, number of cases, use of intrauterine device (IUD), final and initial diagnosis, and method of diagnosis. Results 63 articles met the search criteria, of which 55 reported clinical cases and 8 reported cross-sectional studies. Conclusions Pelvic actinomycosis is confusing to diagnose and should be considered in the differential diagnosis of pelvic chronic inflammatory lesions. It is commonly diagnosed through a histological report, obtained after a surgery subsequent to an erroneous initial diagnosis. A bacterial culture in anaerobic medium could be useful for the diagnosis but requires a controlled technique and should be performed using specialised equipment. PMID:28684963

Does Angiotensin-Converting Enzyme Inhibitor and β-Blocker Use Reduce the Risk of Primary Liver Cancer? A Case-Control Study Using the U.K. Clinical Practice Research Datalink.

PubMed

Hagberg, Katrina Wilcox; Sahasrabuddhe, Vikrant V; McGlynn, Katherine A; Jick, Susan S

2016-02-01

It has been suggested that use of the antihypertensive drugs angiotensin-converting enzyme (ACE) inhibitors and β-blockers may decrease the risk of primary liver cancer; thus, the objective of this study was to evaluate whether use of ACE inhibitors and/or β-blockers is associated with a lower risk of liver cancer. Nested case-control study. United Kingdom Clinical Practice Research Datalink. We identified 490 cases with hypertension and a first-time (incident) diagnosis of primary liver cancer between 1988 and 2011. To account for an induction period, the index date was defined as the date of the first recorded liver cancer diagnosis minus 1 year. Controls were selected from patients with hypertension in the CPRD during the study period with a recorded diagnosis of hypertension who had no diagnosis of liver cancer and were free of any other cancer (except nonmelanoma skin cancer) before the index date; they were matched up to a 4:1 ratio to cases based on index date (same index date as that of their matched case), age (same year of birth), sex, general practice, and number of years of recorded history in the CPRD before the index date (1909 controls). Both cases and controls were required to have at least 2 years of recorded activity in the database before the index date. Exposure was defined as receipt of two or more prescriptions for ACE inhibitors and/or β-blockers before the index date; the reference group was nonuse (0-1 prescription) of ACE or β-blocker prescriptions before the index date. We also examined the effect of duration of use and, separately, the effect of individual drugs within each medication class on risk of liver cancer, and conducted analyses restricted to patients without liver disease or diabetes mellitus. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). No association was found between use of ACE inhibitors and/or β-blockers and the risk of liver cancer compared with nonuse (adjusted OR 1.14, 95% CI 0.85-1.55). No significant differences were noted in risk by duration of use or by individual drugs, or after restricting the analyses to patients without diabetes or liver disease. Use of ACE inhibitors and/or β-blockers was not associated with reduced risk of primary liver cancer compared with nonuse of these drugs in persons with hypertension. © 2016 Pharmacotherapy Publications, Inc.

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

Structural alterations of faecal and mucosa-associated bacterial communities in irritable bowel syndrome.

PubMed

Durbán, Ana; Abellán, Juan J; Jiménez-Hernández, Nuria; Salgado, Patricia; Ponce, Marta; Ponce, Julio; Garrigues, Vicente; Latorre, Amparo; Moya, Andrés

2012-04-01

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder in western countries. Previous studies on IBS, mostly based on faecal samples, suggest alterations in the intestinal microbiota. However, no consensus has been reached regarding the association between specific bacteria and IBS. We explore the alterations of intestinal bacterial communities in IBS using massive sequencing of amplified 16S rRNA genes. Mucosal biopsies of the ascending and descending colon and faeces from 16 IBS patients and 9 healthy controls were analysed. Strong inter-individual variation was observed in the composition of the bacterial communities in both patients and controls. These communities showed less diversity in IBS cases. There were larger differences in the microbiota composition between biopsies and faeces than between patients and controls. We found a few over-represented and under-represented taxa in IBS cases with respect to controls. The detected alterations varied by site, with no changes being consistent across sample types. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

Data Management and Data Quality in PERCH, a Large International Case-Control Study of Severe Childhood Pneumonia.

PubMed

Watson, Nora L; Prosperi, Christine; Driscoll, Amanda J; Higdon, Melissa M; Park, Daniel E; Sanza, Megan; DeLuca, Andrea N; Awori, Juliet O; Goswami, Doli; Hammond, Emily; Hossain, Lokman; Johnson, Catherine; Kamau, Alice; Kuwanda, Locadiah; Moore, David P; Neyzari, Omid; Onwuchekwa, Uma; Parker, David; Sapchookul, Patranuch; Seidenberg, Phil; Shamsul, Arifin; Siazeele, Kazungu; Srisaengchai, Prasong; Sylla, Mamadou; Levine, Orin S; Murdoch, David R; O'Brien, Katherine L; Wolff, Mark; Deloria Knoll, Maria

2017-06-15

The Pneumonia Etiology Research for Child Health (PERCH) study is the largest multicountry etiology study of pediatric pneumonia undertaken in the past 3 decades. The study enrolled 4232 hospitalized cases and 5325 controls over 2 years across 9 research sites in 7 countries in Africa and Asia. The volume and complexity of data collection in PERCH presented considerable logistical and technical challenges. The project chose an internet-based data entry system to allow real-time access to the data, enabling the project to monitor and clean incoming data and perform preliminary analyses throughout the study. To ensure high-quality data, the project developed comprehensive quality indicator, data query, and monitoring reports. Among the approximately 9000 cases and controls, analyzable laboratory results were available for ≥96% of core specimens collected. Selected approaches to data management in PERCH may be extended to the planning and organization of international studies of similar scope and complexity. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Possible roles of bilirubin and breast milk in protection against retinopathy of prematurity.

PubMed

Kao, Joanna S; Dawson, Jeffrey D; Murray, Jeffrey C; Dagle, John M; Berends, Susan K; Gillen, Susan B; Bell, Edward F

2011-03-01

To explore the association of serum bilirubin level and breast milk feeding with retinopathy of prematurity (ROP) in preterm infants. We conducted a case-control study to examine the independent and combined effects of serum bilirubin and breast milk feeding on ROP risk in infants <32 weeks gestation or with birth weight <1500 g. Cases (66 infants with ROP) were matched with controls (66 infants without ROP) based on factors known to affect ROP risk. When analysed using the paired t-test, the peak bilirubin levels were lower in ROP cases than in controls (mean 7.2 vs. 7.9 mg/dL; p = 0.045). Using conditional logistic regression, we found a negative association between highest serum bilirubin level and risk of ROP (OR = 0.82 per 1-mg/dL change in bilirubin; p = 0.06). There was no significant association between breast milk feeding and risk of ROP. Bilirubin may help to protect preterm infants against ROP. © 2010 The Author(s)/Acta Paediatrica © 2010 Foundation Acta Paediatrica.

Cost of malaria control in China: Henan's consolidation programme from community and government perspectives.

PubMed Central

Jackson, Sukhan; Sleigh, Adrian C.; Liu, Xi-Li

2002-01-01

OBJECTIVE: To assist with strategic planning for the eradication of malaria in Henan Province, China, which reached the consolidation phase of malaria control in 1992, when only 318 malaria cases were reported. METHODS: We conducted a prospective two-year study of the costs for Henan's malaria control programme. We used a cost model that could also be applied to other malaria programmes in mainland China, and analysed the cost of the three components of Henan's malaria programme: suspected malaria case management, vector surveillance, and population blood surveys. Primary cost data were collected from the government, and data on suspected malaria patients were collected in two malaria counties (population 2 093 100). We enlisted the help of 260 village doctors in six townships or former communes (population 247 762), and studied all 12 325 reported cases of suspected malaria in their catchment areas in 1994 and 1995. FINDINGS: The average annual government investment in malaria control was estimated to be US$ 111 516 (case-management 59%; active blood surveys 25%; vector surveillance 12%; and contingencies and special projects 4%). The average cost (direct and indirect) for patients seeking treatment for suspected malaria was US$ 3.48, equivalent to 10 days' income for rural residents. Each suspected malaria case cost the government an average of US$ 0.78. CONCLUSION: Further cuts in government funding will increase future costs when epidemic malaria returns; investment in malaria control should therefore continue at least at current levels of US$ 0.03 per person at risk. PMID:12219157

Risk Factors for Border Malaria in a Malaria Elimination Setting: A Retrospective Case-Control Study in Yunnan, China

PubMed Central

Xu, Jian-Wei; Liu, Hui; Zhang, Yu; Guo, Xiang-Rui; Wang, Jia-Zhi

2015-01-01

A retrospective case-control study was conducted to identify risk factors for border malaria in a malaria elimination setting of Yunnan Province, China. The study comprised 214 cases and 428 controls. The controls were individually matched to the cases on the basis of residence, age, and gender. In addition, statistical associations are based on matched analyses. The frequencies of imported, male, adult, and vivax malaria cases were respectively 201 (93.9%), 194 (90.7%), 210 (98.1%), and 176 (82.2%). Overnight stay in Myanmar within the prior month was independently associated with malaria infection (odds ratio [OR] 159.5, 95% confidence interval [CI] 75.1–338.9). In particular, stays in lowland and foothill (OR 5.5, 95% CI 2.5–11.8) or mid-hill (OR 42.8, 95% CI 5.1–319.8) areas, or near streamlets (OR 15.3, 95% CI 4.3–55.2) or paddy field or pools (OR10.1, 95% CI 4.4–55.8) were found to be independently associated with malaria. Neither forest exposure nor use of vector control measures was associated with malaria. In conclusion, travel to lowland and foothill or mid-hill hyperendemic areas, especially along the waterside in Myanmar, was found to be the highest risk factor for malaria. In considering the limitations of the study, further investigations are needed to identify the major determinants of malaria risk and develop new strategies for malaria elimination on China-Myanmar border. PMID:25601994

Exploring single nucleotide polymorphisms previously related to obesity and metabolic traits in pediatric-onset type 2 diabetes.

PubMed

Miranda-Lora, América Liliana; Cruz, Miguel; Aguirre-Hernández, Jesús; Molina-Díaz, Mario; Gutiérrez, Jorge; Flores-Huerta, Samuel; Klünder-Klünder, Miguel

2017-07-01

To evaluate the association of 64 obesity-related polymorphisms with pediatric-onset type 2 diabetes and other glucose- and insulin-related traits in Mexican children. Case-control and case-sibling designs were followed. We studied 99 patients with pediatric-onset type 2 diabetes, their siblings (n = 101) without diabetes, 83 unrelated pediatric controls and 137 adult controls. Genotypes were determined for 64 single nucleotide polymorphisms, and a possible association was examined between those genotypes and type 2 diabetes and other quantitative traits, after adjusting for age, sex and body mass index. In the case-pediatric control and case-adult control analyses, five polymorphisms were associated with increased likelihood of pediatric-onset type 2 diabetes; only one of these polymorphisms (CADM2/rs1307880) also showed a consistent effect in the case-sibling analysis. The associations in the combined analysis were as follows: ADORA1/rs903361 (OR 1.9, 95% CI 1.2; 3.0); CADM2/rs13078807 (OR 2.2, 95% CI 1.2; 4.0); GNPDA2/rs10938397 (OR 2.2, 95% CI 1.4; 3.7); VEGFA/rs6905288 (OR 1.4, 95% CI 1.1; 2.1) and FTO/rs9939609 (OR 1.8, 95% CI 1.0; 3.2). We also identified 16 polymorphisms nominally associated with quantitative traits in participants without diabetes. ADORA/rs903361, CADM2/rs13078807, GNPDA2/rs10938397, VEGFA/rs6905288 and FTO/rs9939609 are associated with an increased risk of pediatric-onset type 2 diabetes in the Mexican population.

Parental occupational pesticide exposure and the risk of childhood leukemia in the offspring: Findings from the Childhood Leukemia International Consortium

PubMed Central

Bailey, Helen D; Fritschi, Lin; Infante-Rivard, Claire; Glass, Deborah C; Miligi, Lucia; Dockerty, John D; Lightfoot, Tracy; Clavel, Jacqueline; Roman, Eve; Spector, Logan G; Kaatsch, Peter; Metayer, Catherine; Magnani, Corrado; Milne, Elizabeth; Polychronopoulou, Sophia; Simpson, Jill; Rudant, Jérémie; Sidi, Vasiliki; Rondelli, Roberto; Orsi, Laurent; Kang, Alice; Petridou, Eleni; Schüz, Joachim

2014-01-01

Maternal occupational pesticide exposure during pregnancy and/or paternal occupational pesticide exposure around conception have been suggested to increase risk of leukemia in the offspring. With a view to providing insight in this area we pooled individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium (CLIC). Occupational data were harmonized to a compatible format. Pooled individual analyses were undertaken using unconditional logistic regression. Using exposure data from mothers of 8,236 cases, and 14,850 controls, and from fathers of 8,169 cases and 14,201 controls the odds ratio (OR) for maternal exposure during pregnancy and the risk of acute lymphoblastic leukemia (ALL) was 1.01 (95% confidence interval (CI) 0.78, 1.30) and for paternal exposure around conception 1.20 (95% 1.06, 1.38). For acute myeloid leukemia (AML), the OR for maternal exposure during pregnancy was 1.94 (CI 1.19, 3.18) and for paternal exposure around conception 0.91 (CI 0.66, 1.24.) based on data from 1,329 case and 12,141 control mothers, and 1,231 case and 11,383 control fathers. Our finding of a significantly increased risk of AML in the offspring with maternal exposure to pesticides during pregnancy is consistent with previous reports. We also found a slight increase in risk of ALL with paternal exposure around conception which appeared to be more evident in children diagnosed at the age of five years or more and those with T cell ALL which raises interesting questions on possible mechanisms. PMID:24700406

The relationship between prior antimicrobial prescription and meningitis: a case-control study.

PubMed

Armstrong, David; Ashworth, Mark; Dregan, Alex; White, Patrick

2016-04-01

Recent research into the role of the human microbiome in maintaining health has identified the potentially harmful impact of antimicrobials. The association with bacterial and viral meningitis following antimicrobial prescription during the previous year was investigated to determine whether antimicrobials have a deleterious effect on the nasopharyngeal microbiome. A case-control study (1:4 cases to controls) was conducted examining the rate of previous antimicrobial exposure in cases of meningitis and in a matched control group. Data from a UK primary care clinical database were analysed using conditional logistic regression. A total of 7346 cases of meningitis were identified, 3307 (45%) viral, 1812 (25%) bacterial, and 2227 (30%) unspecified. The risks of viral (adjusted odds ratio [AOR] 2.45; 95% confidence interval [CI] = 2.24 to 2.68) or bacterial (AOR 1.98; 95% CI = 1.71 to 2.30) meningitis were both increased following antimicrobial prescription in the preceding year. Patients who received ≥4 antimicrobial prescriptions in the preceding year were at significantly increased risk of all types of meningitis (AOR 2.85; 95% CI = 2.44 to 3.34), bacterial meningitis (AOR 3.06; 95% CI = 2.26 to 4.15) and viral meningitis (AOR 3.23; 95% CI = 2.55 to 4.08) compared to their matched controls. There was an increased risk of meningitis following antimicrobial prescription in the previous year. It is possible that this increase was due to an effect of antimicrobials on the microbiome or reflected an increased general susceptibility to infections in these patients. © British Journal of General Practice 2016.

Characterizing mammographic images by using generic texture features

PubMed Central

2012-01-01

Introduction Although mammographic density is an established risk factor for breast cancer, its use is limited in clinical practice because of a lack of automated and standardized measurement methods. The aims of this study were to evaluate a variety of automated texture features in mammograms as risk factors for breast cancer and to compare them with the percentage mammographic density (PMD) by using a case-control study design. Methods A case-control study including 864 cases and 418 controls was analyzed automatically. Four hundred seventy features were explored as possible risk factors for breast cancer. These included statistical features, moment-based features, spectral-energy features, and form-based features. An elaborate variable selection process using logistic regression analyses was performed to identify those features that were associated with case-control status. In addition, PMD was assessed and included in the regression model. Results Of the 470 image-analysis features explored, 46 remained in the final logistic regression model. An area under the curve of 0.79, with an odds ratio per standard deviation change of 2.88 (95% CI, 2.28 to 3.65), was obtained with validation data. Adding the PMD did not improve the final model. Conclusions Using texture features to predict the risk of breast cancer appears feasible. PMD did not show any additional value in this study. With regard to the features assessed, most of the analysis tools appeared to reflect mammographic density, although some features did not correlate with PMD. It remains to be investigated in larger case-control studies whether these features can contribute to increased prediction accuracy. PMID:22490545

MTHFR Gene Polymorphism-Mutations and Air Pollution as Risk Factors for Breast Cancer

PubMed Central

Gonzales, Mildred C.; Yu, Pojui; Shiao, S. Pamela K.

2017-01-01

Background The methylenetetrahydrofolate reductase gene (MTHFR) is one of the most investigated genes associated with breast cancer for its role in epigenetic pathways. Objectives The objectives of this metaprediction study were to examine the polymorphism-mutation risk subtypes of MTHFR and air pollution as contributing factors for breast cancer. Methods For triangulation purposes in metapredictive analyses, we used a recursive partition tree, nonlinear association curve fit, and heat maps for data visualization, in addition to the conventional comparison procedure and pooled analyses. Results We included 36,683 breast cancer cases and 40,689 controls across 82 studies for MTHFR 677 and 23,252 cases and 27,094 controls across 50 studies for MTHFR 1298. MTHFR 677 TT was a risk genotype for breast cancer (p = .0004) and in the East Asian subgroup (p = .005). On global maps, the most polymorphism-mutations on MTHFR 677 TT were found in the Middle East, Europe, Asia, and the Americas, whereas the most mutations on MTHFR 1298 CC were located in Europe and the Middle East for the control group. The geographic information system maps further revealed that MTHFR 677 TT mutations yielded a higher risk of breast cancer for Australia, East Asia, the Middle East, South Europe, Morocco, and the Americas and that MTHFR 1298 CC mutations yielded a higher risk in Asia, the Middle East, South Europe, and South America. Metapredictive analysis revealed that air pollution level was significantly associated with MTHFR 677 TT polymorphism-mutation genotype. Discussion We present the most comprehensive analyses to date of MTHFR polymorphism-mutations and breast cancer risk. Future nursing studies are needed to investigate the health impact on breast cancer of epigenetics and air pollution across populations. PMID:28114181

MTHFR Gene Polymorphism-Mutations and Air Pollution as Risk Factors for Breast Cancer: A Metaprediction Study.

PubMed

Gonzales, Mildred C; Yu, Pojui; Shiao, S Pamela K

The methylenetetrahydrofolate reductase gene (MTHFR) is one of the most investigated genes associated with breast cancer for its role in epigenetic pathways. The objectives of this metaprediction study were to examine the polymorphism-mutation risk subtypes of MTHFR and air pollution as contributing factors for breast cancer. For triangulation purposes in metapredictive analyses, we used a recursive partition tree, nonlinear association curve fit, and heat maps for data visualization, in addition to the conventional comparison procedure and pooled analyses. We included 36,683 breast cancer cases and 40,689 controls across 82 studies for MTHFR 677 and 23,252 cases and 27,094 controls across 50 studies for MTHFR 1298. MTHFR 677 TT was a risk genotype for breast cancer (p = .0004) and in the East Asian subgroup (p = .005). On global maps, the most polymorphism-mutations on MTHFR 677 TT were found in the Middle East, Europe, Asia, and the Americas, whereas the most mutations on MTHFR 1298 CC were located in Europe and the Middle East for the control group. The geographic information system maps further revealed that MTHFR 677 TT mutations yielded a higher risk of breast cancer for Australia, East Asia, the Middle East, South Europe, Morocco, and the Americas and that MTHFR 1298 CC mutations yielded a higher risk in Asia, the Middle East, South Europe, and South America. Metapredictive analysis revealed that air pollution level was significantly associated with MTHFR 677 TT polymorphism-mutation genotype. We present the most comprehensive analyses to date of MTHFR polymorphism-mutations and breast cancer risk. Future nursing studies are needed to investigate the health impact on breast cancer of epigenetics and air pollution across populations.

Achievement of malaria pre-elimination in Cape Verde according to the data collected from 2010 to 2016.

PubMed

DePina, Adilson José; Niang, El Hadji Amadou; Barbosa Andrade, Alex Jailson; Dia, Abdoulaye Kane; Moreira, Antonio; Faye, Ousmane; Seck, Ibrahima

2018-06-19

Malaria, despite being preventable and treatable, continues to be a major public health problem worldwide. The archipelago nation of Cape Verde is in a malaria pre-elimination phase with the highest potential to achieve the target goal of elimination in 2020. Nationwide malaria epidemiological data were obtained from the Cape Verde health information system that includes the individual malaria case notification system from all of the country's health structures. Each case is reported to the surveillance service then to the National Malaria Control Programme, which allowed for compilation in the national malaria case database. The database was analysed to assess the origin of the malaria cases, and incidence was calculated from 2010 to 2016 by sex and age. The health centre, health district and month of diagnosis were evaluated, as well as the sex and the age of the patients, allowing a direct descriptive analysis of national data to provide an up-to-date malaria epidemiological profile of the country. Malaria cases were classified as imported or indigenous, and then, geographical analyses were performed using a unique Geographical National Code with Quantum Geographic Information System 2.16.2 software to map the cases by municipalities. The overall temporal evolution of cases was analysed to assess their monthly and yearly variations from 2010 to 2016. Malaria is unstable in Cape Verde, with inter-annual variation and the majority of infections occurring in adult males (> 20 years). The indigenous cases are restricted to Santiago (96%) and Boavista (4%), while imported cases were recorded in all the nine inhabited islands, originating from neighbouring countries with ongoing malaria transmission; from Lusophone countries (25% from Angola, 25% from Guinea-Bissau), followed by the Republic of Senegal (12%) and Equatorial Guinea (10%). In 2010-2012, more imported (93 cases) than indigenous cases (26 cases) were observed; conversely, in 2013 and 2014, more indigenous cases (49) than imported cases (42) were reported. In 2015 there were 20 imported cases and only 7 indigenous cases. Finally, in 2016, there were 47 indigenous cases and 28 imported cases. The mapping of cases by municipality and country of origin was possible with GIS analyses. While Cape Verde remains on track to achieve malaria elimination by 2020 owing to the reduction of the annual incidence to below 0.1%, the country still records cases of indigenous and imported malaria. However, the indigenous cases are exclusively confined to the Santiago and Boavista islands, while the imported cases recorded nationwide originate only from the African continent, mainly from adult men from the Lusophone countries. Cape Verde needs to target interventions to remove residual foci on Santiago and Boavista islands to reduce malaria lethality to zero and prevent its reintroduction from African countries via transmission across the archipelago. Cape Verde is a good example of local authority's commitment to tackle malaria and work towards its elimination by strengthening the health and surveillance systems.

A polymorphism in the haptoglobin, haptoglobin related protein locus is associated with risk of human sleeping sickness within Cameroonian populations.

PubMed

Ofon, Elvis; Noyes, Harry; Mulindwa, Julius; Ilboudo, Hamidou; Simuunza, Martin; Ebo'o, Vincent; Njiokou, Flobert; Koffi, Mathurin; Bucheton, Bruno; Fogue, Pythagore; Hertz-Fowler, Christiane; MacLeod, Annette; Simo, Gustave

2017-10-01

Human African Trypanosomiasis (HAT) is a neglected disease targeted for elimination as a public health problem by 2020. Elimination requires a better understanding of the epidemiology and clinical evolution of HAT. In addition to the classical clinical evolution of HAT, asymptomatic carriers and spontaneous cure have been reported in West Africa. A genetic component to human susceptibility to HAT has been suggested to explain these newly observed responses to infection. In order to test for genetic associations with infection response, genetic polymorphism in 17 genes were tested (APOL1, IL1B, IL4, IL4R, IL6, IL8, IL12B, IL12RB1, IL10, TNFA, INFG, MIF, HLA-G, HLA-A, HP, HPR and CFH). A case-control study was performed on 180 blood samples collected from 56 cases and 124 controls from Cameroon. DNA was extracted from blood samples. After quality control, 25 samples (24 controls and 1 case) were eliminated. The genotyping undertaken on 155 individuals including 55 cases and 100 controls were investigated at 96 loci (88 SNPs and 8 indels) located on 17 genes. Associations between these loci and HAT were estimated via a case-control association test. Analyses of 64 SNPs and 4 indels out of 96 identified in the selected genes reveal that the minor allele (T) of rs8062041 in haptoglobin (HP) appeared to be protective against HAT (p = 0.0002395, OR 0.359 (CI95 [0.204-0.6319])); indicating higher frequency in cases compared to controls. This minor allele with adjusted p value of 0.0163 is associated with a lower risk (protective effect) of developing sleeping sickness. The haptoglobin related protein HPR and HP are tightly linked and both are duplicated in some people and may lead to higher activity. This increased production could be responsible of the protection associated with rs8062041 even though this SNP is within HP.

A polymorphism in the haptoglobin, haptoglobin related protein locus is associated with risk of human sleeping sickness within Cameroonian populations

PubMed Central

Ofon, Elvis; Noyes, Harry; Mulindwa, Julius; Ilboudo, Hamidou; Simuunza, Martin; Ebo’o, Vincent; Njiokou, Flobert; Koffi, Mathurin; Bucheton, Bruno; Fogue, Pythagore; Hertz-Fowler, Christiane; MacLeod, Annette

2017-01-01

Background Human African Trypanosomiasis (HAT) is a neglected disease targeted for elimination as a public health problem by 2020. Elimination requires a better understanding of the epidemiology and clinical evolution of HAT. In addition to the classical clinical evolution of HAT, asymptomatic carriers and spontaneous cure have been reported in West Africa. A genetic component to human susceptibility to HAT has been suggested to explain these newly observed responses to infection. In order to test for genetic associations with infection response, genetic polymorphism in 17 genes were tested (APOL1, IL1B, IL4, IL4R, IL6, IL8, IL12B, IL12RB1, IL10, TNFA, INFG, MIF, HLA-G, HLA-A, HP, HPR and CFH). Methodology A case-control study was performed on 180 blood samples collected from 56 cases and 124 controls from Cameroon. DNA was extracted from blood samples. After quality control, 25 samples (24 controls and 1 case) were eliminated. The genotyping undertaken on 155 individuals including 55 cases and 100 controls were investigated at 96 loci (88 SNPs and 8 indels) located on 17 genes. Associations between these loci and HAT were estimated via a case-control association test. Results Analyses of 64 SNPs and 4 indels out of 96 identified in the selected genes reveal that the minor allele (T) of rs8062041 in haptoglobin (HP) appeared to be protective against HAT (p = 0.0002395, OR 0.359 (CI95 [0.204–0.6319])); indicating higher frequency in cases compared to controls. This minor allele with adjusted p value of 0.0163 is associated with a lower risk (protective effect) of developing sleeping sickness. Conclusion The haptoglobin related protein HPR and HP are tightly linked and both are duplicated in some people and may lead to higher activity. This increased production could be responsible of the protection associated with rs8062041 even though this SNP is within HP. PMID:29077717

Maternal Diabetes and the Risk of Autism Spectrum Disorders in the Offspring: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Xu, Guifeng; Jing, Jin; Bowers, Katherine; Liu, Buyun; Bao, Wei

2014-01-01

We performed a systematic literature search regarding maternal diabetes before and during pregnancy and the risk of autism spectrum disorders (ASD) in the offspring. Of the 178 potentially relevant articles, 12 articles including three cohort studies and nine case-control studies were included in the meta-analysis. Both the meta-analyses of cohort…

Inverse association between dietary vitamin D and risk of cutaneous melanoma in a northern Italy population

PubMed Central

Vinceti, Marco; Malagoli, Carlotta; Fiorentini, Chiara; Longo, Caterina; Crespi, Catherine M.; Albertini, Giuseppe; Ricci, Cinzia; Lanzoni, Anna; Reggiani, Maurizio; Virgili, Annarosa; Osti, Federica; Lombardi, Mara; Santini, Marcello; Fanti, Pier Alessandro; Dika, Emi; Sieri, Sabina; Krogh, Vittorio; Seidenari, Stefania; Pellacani, Giovanni

2010-01-01

The possibility of an inverse association between vitamin D and risk of cancer and, in particular, of cutaneous malignant melanoma has been suggested, but results of epidemiologic studies are still conflicting. We examined the relation between dietary vitamin D intake and melanoma risk through a population-based case-control study (380 cases, 719 controls) in a northern region of Italy, a country with average vitamin D intake lower than in northern Europe or the US. We assessed average daily intake of vitamin D from foodstuffs using the European Prospective Investigation into Cancer and Nutrition (EPIC) semiquantitative food frequency questionnaire. In this population, levels of vitamin D intake were considerably lower than those observed in recent US studies. We found an inverse relation between dietary vitamin D and melanoma risk in the sample as a whole, in both crude and adjusted analyses. In sex and age-specific analyses, this association appeared to be stronger among males and among older subjects. These findings suggest that, at the relatively low levels of intake observed in this sample, an inverse relation between dietary vitamin D and risk of cutaneous malignant melanoma may exist. PMID:21541899

Application of logistic regression to case-control association studies involving two causative loci.

PubMed

North, Bernard V; Curtis, David; Sham, Pak C

2005-01-01

Models in which two susceptibility loci jointly influence the risk of developing disease can be explored using logistic regression analysis. Comparison of likelihoods of models incorporating different sets of disease model parameters allows inferences to be drawn regarding the nature of the joint effect of the loci. We have simulated case-control samples generated assuming different two-locus models and then analysed them using logistic regression. We show that this method is practicable and that, for the models we have used, it can be expected to allow useful inferences to be drawn from sample sizes consisting of hundreds of subjects. Interactions between loci can be explored, but interactive effects do not exactly correspond with classical definitions of epistasis. We have particularly examined the issue of the extent to which it is helpful to utilise information from a previously identified locus when investigating a second, unknown locus. We show that for some models conditional analysis can have substantially greater power while for others unconditional analysis can be more powerful. Hence we conclude that in general both conditional and unconditional analyses should be performed when searching for additional loci.

The consumption of coffee and black tea and the risk of lung cancer.

PubMed

Pasquet, Romain; Karp, Igor; Siemiatycki, Jack; Koushik, Anita

2016-11-01

Coffee and black tea are among the most consumed beverages worldwide. Although their potential role in lung cancer occurrence has been investigated in several studies, results have been inconclusive. We investigated the associations between intake of coffee and black tea with lung cancer in a population-based case-control study in Montreal, Canada. These analyses included 1130 cases and 1483 controls. Adjusted odds ratios (ORs) were estimated between four metrics of coffee and black tea consumption (frequency, average daily amount, duration, and cumulative amount) and lung cancer, using unconditional logistic regression. The adjusted ORs (95% confidence intervals) for lung cancer comparing daily to never consumers were 0.73 (0.49-1.10) for coffee and 1.05 (0.85-1.31) for black tea. Analyses of other metrics did not reveal any clear patterns of increasing or decreasing risk with increasing amounts or duration of consumption. There was no strong evidence of OR modification by sex or smoking level. The OR estimates did not materially differ by histological subtype for either of the beverages. Our results do not provide strong support for associations between consumption of coffee and black tea and lung cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

The constellation of dietary factors in adolescent acne: a semantic connectivity map approach.

PubMed

Grossi, E; Cazzaniga, S; Crotti, S; Naldi, L; Di Landro, A; Ingordo, V; Cusano, F; Atzori, L; Tripodi Cutrì, F; Musumeci, M L; Pezzarossa, E; Bettoli, V; Caproni, M; Bonci, A

2016-01-01

Different lifestyle and dietetic factors have been linked with the onset and severity of acne. To assess the complex interconnection between dietetic variables and acne. This was a reanalysis of data from a case-control study by using a semantic connectivity map approach. 563 subjects, aged 10-24 years, involved in a case-control study of acne between March 2009 and February 2010, were considered in this study. The analysis evaluated the link between a moderate to severe acne and anthropometric variables, family history and dietetic factors. Analyses were conducted by relying on an artificial adaptive system, the Auto Semantic Connectivity Map (AutoCM). The AutoCM map showed that moderate-severe acne was closely associated with family history of acne in first degree relatives, obesity (BMI ≥ 30), and high consumption of milk, in particular skim milk, cheese/yogurt, sweets/cakes, chocolate, and a low consumption of fish, and limited intake of fruits/vegetables. Our analyses confirm the link between several dietetic items and acne. When providing care, dermatologists should also be aware of the complex interconnection between dietetic factors and acne. © 2014 European Academy of Dermatology and Venereology.

Evaluation of familial aggregation, vegetable consumption, legumes consumption, and physical activity on functional constipation in families of children with functional constipation versus children without constipation.

PubMed

Dehghani, Seyed Mohsen; Moravej, Hossein; Rajaei, Elahe; Javaherizadeh, Hazhir

2015-01-01

Constipation is a frequent complication in paediatrics. Most of the constipation is functional. Functional constipation constitutes 25% of visits in paediatric gastroenterology clinics. Two studies were published regarding aggregation or clustering of functional constipation. Only one of these research projects was about a paediatric population. To elucidate the cluster pattern of constipation among the families of children with constipation. This case-control study was carried out on the families of 37 children < 18 years old with chronic functional constipation and the families of 37 healthy children as controls. Cases were enrolled in the study according to Rome III criteria for constipation. The control group was selected from children < 18 years old who visited the well baby clinic of the university. Parents and siblings were evaluated regarding constipation. Rome II and III were used for evaluation of constipation for adults and children, respectively. Data was analysed using SPSS (Chicago, IL, USA). The χ(2) and t-test were used for comparison. Physical activity and vegetable consumption were seen more frequently in the control group compared to the cases, but these differences were statistically insignificant. Constipation in mothers was significantly higher in the case group compared to the control group (p = 0.015). There was no significant difference between the two groups regarding exercise and vegetable consumption. The frequency of constipation among mothers was significantly higher in the case group compared to the control group. Another study is recommended in a larger population for evaluation of genetic background, diet, physical activity, and familial clustering among mothers of children with constipation.

The Epidemiological Importance of Bats in the Transmission of Rabies to Dogs and Cats in the State of São Paulo, Brazil, Between 2005 and 2014.

PubMed

Castilho, J G; de Souza, D N; Oliveira, R N; Carnieli, P; Batista, H B C R; Pereira, P M C; Achkar, S M; Macedo, C I

2017-09-01

In Brazil, rabies control in dogs and cats was pioneered by the state of São Paulo with the adoption of the Pan American Health Organization recommendations for prophylaxis and control, which led to a reduction in rabies cases from 1994 onwards. As a result of these measures, the rabies virus (RABV) genetic lineage associated with dogs has not been found in the state since 1998, and all the cases in domestic animals reported since then have been caused by bat-associated lineages of RABV. In the light of this, this study sought to investigate rabies cases in dogs and cats in the state of São Paulo between 2005 and 2014 and identify the associated transmission cycles by characterizing the RABV lineages responsible for these cases. Nine samples from dogs (n = 5) and from cats (n = 4) were collected between 2005 and 2014. The tenth animal, a rabid cat, was analysed by a different laboratory. The N gene nucleotide sequences obtained were analysed with the neighbor-joining algorithm and Kimura 2-parameter model using the MEGA 6 program. Phylogenetic analysis revealed that the genetic lineages identified in all the samples were those circulating in Brazilian bats. The findings of this study demonstrate that bats play an important role in the transmission of rabies to domestic animals in São Paulo state and that emphasis should be placed on the implementation of public policies to support surveillance of chiropterans for rabies. © 2016 Blackwell Verlag GmbH.

Space-time epidemiology and effect of meteorological parameters on influenza-like illness in Phitsanulok, a northern province in Thailand.

PubMed

Nimbalkar, Prakash Madhav; Tripathi, Nitin Kumar

2016-11-21

Influenza-like illness (ILI) is an acute respiratory disease that remains a public health concern for its ability to circulate globally affecting any age group and gender causing serious illness with mortality risk. Comprehensive assessment of the spatio-temporal dynamics of ILI is a prerequisite for effective risk assessment and application of control measures. Though meteorological parameters, such as rainfall, average relative humidity and temperature, influence ILI and represent crucial information for control of this disease, the relation between the disease and these variables is not clearly understood in tropical climates. The aim of this study was to analyse the epidemiology of ILI cases using integrated methods (space-time analysis, spatial autocorrelation and other correlation statistics). After 2009s H1N1 influenza pandemic, Phitsanulok Province in northern Thailand was strongly affected by ILI for many years. This study is based on ILI cases in villages in this province from 2005 to 2012. We used highly precise weekly incidence records covering eight years, which allowed accurate estimation of the ILI outbreak. Comprehensive methodology was developed to analyse the global and local patterns of the spread of the disease. Significant space-time clusters were detected over the study region during eight different periods. ILI cases showed seasonal clustered patterns with a peak in 2010 (P>0.05-9.999 iterations). Local indicators of spatial association identified hotspots for each year. Statistically, the weather pattern showed a clear influence on ILI cases and it strongly correlated with humidity at a lag of 1 month, while temperature had a weaker correlation.

Assets and pitfalls of chemical and microscopic analyses on gunshot residues in skeletonized bodies: a report of five cases.

PubMed

Amadasi, Alberto; Gibelli, Daniele; Mazzarelli, Debora; Porta, Davide; Gaudio, Daniel; Salsarola, Dominic; Brandone, Alberto; Rizzi, Agostino; Cattaneo, Cristina

2015-07-01

In case of gunshot wounds, forensic anthropologists and pathologists have many tools at hand, and the assistance that chemical and microscopic investigations can provide in such scenarios is often valuable and crucial. However, the results of such analyses in the search of gunshot residues (GSR) ought not to be acritically considered. We report five cases where chemical (sodium rhodizonate) and microscopic (scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX)) analyses were performed for the search of GSR. Four cases concerned the forensic field and analyses on buried, charred, or submerged remains, whereas one case concerned the historical remains of a soldier of the First World War. In every case, the search for GSR with these techniques showed their persistence even after long periods and preservation in peculiar environments. However, chemical analyses provided their contribution, but in two cases, anthropological analyses provided crucial and solving results. The five cases show the indisputable usefulness of chemical and microscopic analyses in the search of GSR in gunshot wounds and especially how such residues may survive in time and in adverse environmental conditions. However, experts should always be dubious about some pitfalls (such as contamination) one can frequently find in these scenarios.

Achilles or biceps tendon rupture in women and men with type 2 diabetes: A population-based case-control study.

PubMed

Spoendlin, Julia; Meier, Christian; Jick, Susan S; Meier, Christoph R

2016-07-01

Previous studies suggest that diabetes causes alterations in tendon collagen structure, but evidence on how such findings translate into clinical practice is scarce. We aimed to analyze the association between type 2 diabetes and the risk of tendon rupture. We conducted a matched case-control analysis using the UK-based Clinical Practice Research Datalink. Cases (n=7895) were aged 30-89years and had an incident diagnosis of Achilles- or biceps tendon rupture between 1995 and 2013. In multivariable logistic regression analyses we compared the odds of tendon rupture between patients with or without type 2 diabetes, in men and women separately, and taking into account diabetes severity (HbA1c), duration, and antidiabetic drug treatment. Within 165 (7.1%) female cases with type 2 diabetes, odds ratios (ORs) were increased with poorer diabetes control (OR 2.03, 95% CI 1.20-3.41, HbA1c ≥9% [≥75mmol/mol]), longer disease duration (OR 1.60, 95% CI 0.93-2.74, ≥10years), and current insulin use (OR 2.25, 95% CI 1.30-3.90, ≥20 prescriptions). Among 372 (6.7%) male cases, there was no effect of type 2 diabetes on the risk of tendon rupture. Our results suggest that the risk of tendon ruptures may be increased in women with poorly controlled type 2 diabetes, but not in men. Copyright © 2016 Elsevier Inc. All rights reserved.

Analysis of glutathione S-transferase Pi isoform (GSTP1) single-nucleotide polymorphisms and macular telangiectasia type 2.

PubMed

Szental, Joshua A; Baird, Paul N; Richardson, Andrea J; Islam, F M Amirul; Scholl, Hendrik P N; Charbel Issa, Peter; Holz, Frank G; Gillies, Mark; Guymer, Robyn H

2010-12-01

Recent imaging studies have suggested that macular pigment is decreased centrally in macular telangiectasia type 2 (MT2). The uptake of xanthophyll pigment into the macula is thought to be facilitated by a xanthophyll-binding protein (XBP). The Pi isoform of glutathione S-transferase (GSTP1) represents one such XBP with high binding affinity. This case-control study aimed to determine whether two common single-nucleotide polymorphisms (SNPs) of GSTP1 were associated with MT2. DNA samples from 39 cases and 21 controls were collected. Two polymorphic sites of Ile105Val and Ala114Val in exons 5 and 6 respectively, of the GSTP1 gene were analysed. Comparison of alleles and genotypes between cases and controls indicated that there were no statistically significant differences for either the Ile105Val SNP (P=0.43) or the Ala114Val SNP (P=0.85), or for any combinations; however, the homozygous at-risk genotype (GG) of the Ile105Val SNP was present in 8% of cases but absent in controls. This study found no statistically significant association between two common GSTP1 SNPs and MT2; however, a trend towards a greater frequency of the GG genotype of the Ile105Val SNP in cases is of great interest. The biological plausibility of disturbed macular pigment uptake in MT2 makes GSTP1 an excellent candidate gene. Further investigation is warranted in future studies of MT2.

Web survey-based selection of controls for epidemiological analyses of a multi-prefectural outbreak of enterohaemorrhagic Escherichia coli O157 in Japan associated with consumption of self-grilled beef hanging tender.

PubMed

Yahata, Y; Ohshima, N; Odaira, F; Nakamura, N; Ichikawa, H; Matsuno, K; Shuri, J; Toyozawa, T; Terajima, J; Watanabe, H; Nakashima, K; Sunagawa, T; Taniguchi, K; Okabe, N

2018-03-01

An outbreak of enterohaemorrhagic Escherichia coli O157 occurred in multiple prefectures of Japan in November 2009. We conducted two case-control studies with trace-back and trace-forward investigations to determine the source. The case definition was met by 21 individuals; 14 (66.7%) were hospitalised, but no haemolytic uraemic syndrome, acute encephalopathy or deaths occurred. Median age was 23 (range 12-48) years and 14 cases were male (66.7%). No significant associations with food were found in a case-control study by local public health centres, but our matched case-control study using Internet surveys found that beef hanging tender (or hanger steak), derived from the diaphragm of the cattle, was significantly associated with illness (odds ratio = 15.77; 95% confidence interval, 2.00-124.11). Pulsed-field gel electrophoresis analysis of isolates from patients and the suspected food showed five different patterns: two in faecal and food samples, and another three in patient faecal samples only, although there were epidemiological links to the meat consumed at the restaurants. Trace-back investigation implicated a common food processing company from outside Japan. Examination of the logistics of the meat processing company suggested that contamination did not occur in Japan. We concluded that the source of the outbreak was imported hanging tender. This investigation revealed that Internet surveys could be useful for outbreak investigations.

[Health-related quality of life in cases of attention deficit hyperactivity disorder with and without pharmacological treatment].

PubMed

López-Villalobos, José Antonio; Sacristán-Martín, Ana María; Garrido-Redondo, Mercedes; Martínez-Rivera, María Teresa; López-Sánchez, María Victoria; Rodríguez-Molinero, Luis; Camina-Gutiérrez, Ana Belén; Andrés-de Llano, Jesús

2018-06-02

The health-related quality of life (HRQoL) questionnaire is important in order to assess the effects of therapeutic intervention. The aim of this study is to analyse HRQoL, comparing cases of attention deficit hyperactivity disorder (ADHD) treated with methylphenidate (ADHD-T), untreated cases (ADHD-N), and controls. The study included a sample of 228 participants between 8 and 14 years old (114 controls, 57 ADHD-T, and 57 ADHD-N). Consecutive sampling was used in ADHD according to DSM-IV criteria (ADHD Rating Scales IV), and random sampling of controls matched by gender and age. The evaluation of HRQoL was made by using KIDSCREEN-52 parent version. The intensity of ADHD symptoms is significantly lower in ADHD-T than in ADHD-N. There is a moderate significant correlation between greater intensity of ADHD symptoms and worse HRQoL. ADHD cases have significantly worse HRQoL than controls on psychic well-being, mood, relationship with parents and friends, school environment, and social acceptance. The cases of ADHD-T have significantly better HRQoL than ADHD-N in the school dimension, but do not differ significantly in other dimensions of KIDSCREEN-52. It would be advisable that the treatment of ADHD integrates multi-dimensional therapeutic models that improve the basic symptoms of the disorder, as well as the HRQoL. Copyright © 2018. Publicado por Elsevier España, S.L.U.

Detecting space-time cancer clusters using residential histories

NASA Astrophysics Data System (ADS)

Jacquez, Geoffrey M.; Meliker, Jaymie R.

2007-04-01

Methods for analyzing geographic clusters of disease typically ignore the space-time variability inherent in epidemiologic datasets, do not adequately account for known risk factors (e.g., smoking and education) or covariates (e.g., age, gender, and race), and do not permit investigation of the latency window between exposure and disease. Our research group recently developed Q-statistics for evaluating space-time clustering in cancer case-control studies with residential histories. This technique relies on time-dependent nearest neighbor relationships to examine clustering at any moment in the life-course of the residential histories of cases relative to that of controls. In addition, in place of the widely used null hypothesis of spatial randomness, each individual's probability of being a case is instead based on his/her risk factors and covariates. Case-control clusters will be presented using residential histories of 220 bladder cancer cases and 440 controls in Michigan. In preliminary analyses of this dataset, smoking, age, gender, race and education were sufficient to explain the majority of the clustering of residential histories of the cases. Clusters of unexplained risk, however, were identified surrounding the business address histories of 10 industries that emit known or suspected bladder cancer carcinogens. The clustering of 5 of these industries began in the 1970's and persisted through the 1990's. This systematic approach for evaluating space-time clustering has the potential to generate novel hypotheses about environmental risk factors. These methods may be extended to detect differences in space-time patterns of any two groups of people, making them valuable for security intelligence and surveillance operations.

Toxoplasma gondii exposure and Parkinson's disease: a case-control study.

PubMed

Alvarado-Esquivel, Cosme; Méndez-Hernández, Edna Madai; Salas-Pacheco, José Manuel; Ruano-Calderón, Luis Ángel; Hernández-Tinoco, Jesús; Arias-Carrión, Oscar; Sánchez-Anguiano, Luis Francisco; Castellanos-Juárez, Francisco Xavier; Sandoval-Carrillo, Ada Agustina; Liesenfeld, Oliver; Ramos-Nevárez, Agar

2017-02-13

To determine the association between Toxoplasma gondii infection and Parkinson's disease and to investigate whether T. gondii seropositivity is associated with the general characteristics of patients with Parkinson's disease. Case-control study. Cases and controls were enrolled in Durango City, Mexico. 65 patients with Parkinson's disease and 195 age- and gender-matched control subjects without Parkinson's disease. Serum samples of participants were analysed for anti- T. gondii IgG and IgM antibodies by commercially available enzyme-linked immunoassays. Prevalence of T. gondii DNA was determined in seropositive subjects using PCR. The association between clinical data and infection was examined by bivariate analysis. Anti- T. gondii IgG antibodies were found in 6/65 cases (9.2%) and in 21/195 controls (10.8%) (OR 0.84; 95% CI 0.32 to 2.18; p=0.81). The frequency of high (>150 IU/mL) antibody levels was similar among cases and controls (p=0.34). None of the anti- T. gondii IgG positive cases and four of the anti- T. gondii IgG positive controls had anti- T. gondii IgM antibodies (p=0.54). The prevalence of T. gondii DNA was comparable in seropositive cases and controls (16.7% and 25%, respectively; p=1.0). Seroprevalence of T. gondii infection was associated with a young age onset of disease (p=0.03), high Unified Parkinson Disease Rating Scale scores (p=0.04) and depression (p=0.02). Seropositivity to T. gondii infection was lower in patients treated with pramipexole than in patients without this treatment (p=0.01). However, none of the associations remained significant after Bonferroni correction. The results do not support an association between T. gondii infection and Parkinson's disease. However, T. gondii infection might have an influence on certain symptoms of Parkinson's disease. Further research to elucidate the role of T. gondii exposure on Parkinson's disease is warranted. 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/.

Variants in the ATP-Binding Cassette Transporter (ABCA7), Apolipoprotein E ε4, and the Risk of Late-Onset Alzheimer Disease in African Americans

PubMed Central

Reitz, Christiane; Jun, Gyungah; Naj, Adam; Rajbhandary, Ruchita; Vardarajan, Badri Narayan; 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; 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.; Schellenberg, Gerard D.; Mayeux, Richard

2013-01-01

Importance Genetic variants associated with susceptibility to late-onset Alzheimer disease are known for individuals of European ancestry, but whether the same or different variants account for the genetic risk of Alzheimer disease in African American individuals is unknown. Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment. Objective To identify genetic loci associated with late-onset Alzheimer disease in African Americans. Design, Setting, and Participants The Alzheimer Disease Genetics Consortium (ADGC) assembled multiple data sets representing a total of 5896 African Americans (1968 case participants, 3928 control participants) 60 years or older that were collected between 1989 and 2011 at multiple sites. The association of Alzheimer disease with genotyped and imputed single-nucleotide polymorphisms (SNPs) was assessed in case-control and in family-based data sets. Results from individual data sets were combined to perform an inverse variance–weighted meta-analysis, first with genome-wide analyses and subsequently with gene-based tests for previously reported loci. Main Outcomes and Measures Presence of Alzheimer disease according to standardized criteria. Results Genome-wide significance in fully adjusted models (sex, age, APOE genotype, population stratification) was observed for a SNP in ABCA7 (rs115550680, allele = G; frequency, 0.09 cases and 0.06 controls; odds ratio [OR], 1.79 [95% CI, 1.47-2.12]; P = 2.2 × 10–9), which is in linkage disequilibrium with SNPs previously associated with Alzheimer disease in Europeans (0.8

Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis

PubMed Central

Trifan, Anca; Stanciu, Carol; Girleanu, Irina; Stoica, Oana Cristina; Singeap, Ana Maria; Maxim, Roxana; Chiriac, Stefan Andrei; Ciobica, Alin; Boiculese, Lucian

2017-01-01

AIM To perform a systematic review and meta-analysis on proton pump inhibitors (PPIs) therapy and the risk of Clostridium difficile infection (CDI). METHODS We conducted a systematic search of MEDLINE/PubMed and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios (ORs) estimates with 95% confidence intervals (CIs) were calculated using the random effect. Heterogeneity was assessed by I2 test and Cochran’s Q statistic. Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale (NOS). RESULTS Fifty-six studies (40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI (pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control (OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort (OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted (OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted (OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter (OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter (OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years (OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years (OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses (test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies (I2 = 85.4%, P < 0.001) as well as evidence of publication bias (funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal. PMID:29085200

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

Intra- and intertrench variations in flexural bending of the Manila, Mariana and global trenches: implications on plate weakening in controlling trench dynamics

NASA Astrophysics Data System (ADS)

Zhang, Fan; Lin, Jian; Zhou, Zhiyuan; Yang, Hongfeng; Zhan, Wenhuan

2018-02-01

We conducted detailed analyses of a global array of trenches, revealing systematic intra- and intertrench variations in plate bending characteristics. The intratrench variations of the Manila and Mariana Trenches were analysed in detail as end-member cases of the relatively young (16-36 Ma) and old (140-160 Ma) subducting plates, respectively. Meanwhile, the intertrench variability was investigated for a global array of additional trenches including the Philippine, Kuril, Japan, Izu-Bonin, Aleutian, Tonga-Kermadec, Middle America, Peru, Chile, Sumatra and Java Trenches. Results of the analysis show that the trench relief (W0) and width (X0) of all systems are controlled primarily by the faulting-reduced elastic thickness near the trench axis (Tem) and affected only slightly by the initial unfaulted thickness (TeM) of the incoming plate. The reduction in Te has caused significant deepening and narrowing of trench valleys. For the cases of relatively young or old plates, the plate age could be a dominant factor in controlling the trench bending shape, regardless the variations in axial loadings. Our calculations also show that the axial loading and stresses of old subducting plates can vary significantly along the trench axis. In contrast, the young subducting plates show much smaller values and variations in axial loading and stresses.

Draugen HSE-case - occupational health risk management

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

Glas, J.J.P.; Kjaer, E.

1996-12-31

The Draugen HSE-Case serves as a risk management tool. Originally, risk management included only major safety hazards to personnel, environment and assets. Work Environment risks such as ergonomics, psycho-social factors and exposure to chemicals and noise, was not given the same attention. The Draugen HSE-Case addresses this weakness and extends all work environment risks. In order to promote line responsibility and commitment, relevant personnel is involved in the Case development. {open_quotes}THESIS{degrees}, a software application, is used to systematize input and to generate reports. The Draugen HSE-case encompasses: HSE risk analyses related to specific activities; Control of risk related to workmore » environment; Established tolerability criteria; Risk reducing measures; Emergency contingency measures; and Requirements for Competence and Follow-up. The development of Draugen HSE-Case is a continuous process. It will serve to minimize the potential of occupational illnesses, raise general awareness, and make occupational health management more cost-effective.« less

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.

Molecular and mathematical modeling analyses of inter-island transmission of rabies into a previously rabies-free island in the Philippines.

PubMed

Tohma, Kentaro; Saito, Mariko; Demetria, Catalino S; Manalo, Daria L; Quiambao, Beatriz P; Kamigaki, Taro; Oshitani, Hitoshi

2016-03-01

Rabies is endemic in the Philippines and dog bites are a major cause of rabies cases in humans. The rabies control program has not been successful in eliminating rabies because of low vaccination coverage among dogs. Therefore, more effective and feasible strategies for rabies control are urgently required in the country. To control rabies, it is very important to know if inter-island transmission can occur because rabies can become endemic once the virus is introduced in areas that previously had no reported cases. Our molecular epidemiological study suggests that inter-island transmission events can occur; therefore, we further investigated these inter-island transmission using phylogenetic and modeling approaches. We investigate inter-island transmission between Luzon and Tablas Islands in the Philippines. Phylogenetic analysis and mathematical modeling demonstrate that there was a time lag of several months to a year from rabies introduction to initial case detection, indicating the difficulties in recognizing the initial rabies introductory event. There had been no rabies cases reported in Tablas Island; however, transmission chain was sustained on this island after the introduction of rabies virus because of low vaccination coverage among dogs. Across the islands, a rabies control program should include control of inter-island dog transportation and rabies vaccination to avoid viral introduction from the outside and to break transmission chains after viral introduction. However, this program has not yet been completely implemented and transmission chains following inter-island virus transmission are still observed. Local government units try to control dog transport; however, it should be more strictly controlled, and a continuous rabies control program should be implemented to prevent rabies spread even in rabies-free areas. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Integrated analysis of germline and somatic variants in ovarian cancer.

PubMed

Kanchi, Krishna L; Johnson, Kimberly J; Lu, Charles; McLellan, Michael D; Leiserson, Mark D M; Wendl, Michael C; Zhang, Qunyuan; Koboldt, Daniel C; Xie, Mingchao; Kandoth, Cyriac; McMichael, Joshua F; Wyczalkowski, Matthew A; Larson, David E; Schmidt, Heather K; Miller, Christopher A; Fulton, Robert S; Spellman, Paul T; Mardis, Elaine R; Druley, Todd E; Graubert, Timothy A; Goodfellow, Paul J; Raphael, Benjamin J; Wilson, Richard K; Ding, Li

2014-01-01

We report the first large-scale exome-wide analysis of the combined germline-somatic landscape in ovarian cancer. Here we analyse germline and somatic alterations in 429 ovarian carcinoma cases and 557 controls. We identify 3,635 high confidence, rare truncation and 22,953 missense variants with predicted functional impact. We find germline truncation variants and large deletions across Fanconi pathway genes in 20% of cases. Enrichment of rare truncations is shown in BRCA1, BRCA2 and PALB2. In addition, we observe germline truncation variants in genes not previously associated with ovarian cancer susceptibility (NF1, MAP3K4, CDKN2B and MLL3). Evidence for loss of heterozygosity was found in 100 and 76% of cases with germline BRCA1 and BRCA2 truncations, respectively. Germline-somatic interaction analysis combined with extensive bioinformatics annotation identifies 222 candidate functional germline truncation and missense variants, including two pathogenic BRCA1 and 1 TP53 deleterious variants. Finally, integrated analyses of germline and somatic variants identify significantly altered pathways, including the Fanconi, MAPK and MLL pathways.

The Impact Of Palifermin Use On Hematopoietic Cell Transplant Outcomes In Children

PubMed Central

Saber, Wael; Zhang, Mei-Jie; Steinert, Patricia; Chen, Min; Horowitz, Mary M

2016-01-01

Purpose Clinical trials evaluating palifermin have enrolled few pediatric patients precluding safety analyses in large groups of children. We compared hematopoietic cell transplant (HCT) outcomes among pediatric patients from a large database who did or did not receive palifermin as a preventive treatment for oral mucositis. Patients and Methods Pediatric patients and controls, matched for HCT and donor type, disease, disease status and age, were selected from the Center for International Blood and Marrow Transplant Research (CIBMTR) database and a 1:3 matched cohort analysis was performed. Stratified Cox proportional hazards models were built and propensity score adjustments were used to compare overall and disease-free survival outcomes between palifermin-treated and untreated patients. Results Three controls were identified for 90% of palifermin recipients. The remaining cases were matched with two (8%) or one (2%) controls, for a total of 210 palifermin-treated patients matched with 606 controls. Median follow-up was 31 months in cases and 36 months in controls. 57% of patients underwent allogeneic HCT, mostly for acute leukemia, and 43% underwent autologous HCT, mostly for solid tumors. In univariate analyses, two-year survival and disease-free survival rates after allogeneic HCT (58% vs 66%, P = .109; 49% vs 60%, P = .060) and after autologous HCT (73% vs 77%, P = .474; 60% vs 64%, P = .637) were similar between palifermin-treated patients and matched controls. In multivariate analysis, palifermin treatment did not significantly increase the risk of mortality (relative risk [RR] 1.20, 95% CI 0.87–1.66) or relapse (RR 1.12, 95% CI 0.78–1.62) compared with matched controls. No significant differences in rates of acute or chronic graft-vs-host disease (GVHD) were observed between palifermin-treated patients and matched controls. Conclusion Among the pediatric patients undergoing HCT, overall survival, disease-free survival, neutrophil recovery, and GVHD rates were similar between palifermin-treated patients and matched controls. PMID:27090960

Association between IL-1β polymorphisms and gastritis risk: A meta-analysis.

PubMed

Sun, Xiaoming; Cai, Hongxing; Li, Zhouru; Li, Shanshan; Yin, Wenjiang; Dong, Guokai; Kuai, Jinxia; He, Yihui; Jia, Jing

2017-02-01

Helicobacter pylori (H. pylori) infection of the human stomach regularly leads to chronic gastric inflammation. The cytokine gene interleukin (IL)-1β has been implicated in influencing the pathology of inflammation induced by H. pylori infection. Currently, several studies have been carried out to investigate the association of IL-1β-511 (rs16944) and IL-1β-31 (rs1143627) polymorphisms with gastritis risk; however, the results are inconsistent and inconclusive. To assess the effect of IL-1β polymorphisms on gastritis susceptibility, we conducted a meta-analysis. Up to March 15, 2016, 2205 cases and 2289 controls were collected from 12 published case-control studies. Summarized odds ratios and corresponding 95% confidence intervals (CIs) for IL-1β-511 and IL-1β-31 polymorphisms and gastritis risk were estimated using fixed- or random-effects models when appropriate. Heterogeneity was assessed by chi-squared-based Q-statistic test, and the sources of heterogeneity were explored by subgroup analyses and logistic meta-regression analyses. Publication bias was evaluated by Begg funnel plot and Egger test. Sensitivity analyses were also performed. The results provided evidences that the single nucleotide polymorphisms (SNPs) in IL-1β-31 might be associated with the gastritis risk, especially in the Caucasian population, while SNPs in the IL-1β-511 might not be. Our studies may be helpful in supplementing the disease monitoring of gastritis in the future, and additional studies to determine the exact molecular mechanisms might inspire interventions to protect the susceptible subgroups.

Testing self-regulation interventions to increase walking using factorial randomized N-of-1 trials.

PubMed

Sniehotta, Falko F; Presseau, Justin; Hobbs, Nicola; Araújo-Soares, Vera

2012-11-01

To investigate the suitability of N-of-1 randomized controlled trials (RCTs) as a means of testing the effectiveness of behavior change techniques based on self-regulation theory (goal setting and self-monitoring) for promoting walking in healthy adult volunteers. A series of N-of-1 RCTs in 10 normal and overweight adults ages 19-67 (M = 36.9 years). We randomly allocated 60 days within each individual to text message-prompted daily goal-setting and/or self-monitoring interventions in accordance with a 2 (step-count goal prompt vs. alternative goal prompt) × 2 (self-monitoring: open vs. blinded Omron-HJ-113-E pedometer) factorial design. Aggregated data were analyzed using random intercept multilevel models. Single cases were analyzed individually. The primary outcome was daily pedometer step counts over 60 days. Single-case analyses showed that 4 participants significantly increased walking: 2 on self-monitoring days and 2 on goal-setting days, compared with control days. Six participants did not benefit from the interventions. In aggregated analyses, mean step counts were higher on goal-setting days (8,499.9 vs. 7,956.3) and on self-monitoring days (8,630.3 vs. 7,825.9). Multilevel analyses showed a significant effect of the self-monitoring condition (p = .01), the goal-setting condition approached significance (p = .08), and there was a small linear increase in walking over time (p = .03). N-of-1 randomized trials are a suitable means to test behavioral interventions in individual participants.

Genetic Risk Score Analysis in Early-Onset Bipolar Disorder.

PubMed

Croarkin, Paul E; Luby, Joan L; Cercy, Kelly; Geske, Jennifer R; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T; Wagner, Karen Dineen; Walkup, John T; Nassan, Malik M; Cuellar-Barboza, Alfredo B; Casuto, Leah; McElroy, Susan L; Jensen, Peter S; Frye, Mark A; Biernacka, Joanna M

In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with BD, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly "odz, odd Oz/10-m homolog 4 {Drosophila}, ODZ4"]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n = 69); adult patients with BD (n = 732), including a subset with early-onset illness (n = 192); and healthy controls (n = 776). GRS analyses were performed to compare early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. GRS analysis revealed associations of the risk score with early-onset BD (P = .01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset BD with a CACNA1C haplotype (global test, P = .01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset BD (P = .017), which did not remain significant after correction for multiple comparisons. These preliminary analyses suggest that previously identified BD risk loci, especially CACNA1C, have a role in early-onset BD, possibly with stronger effects than for late-onset BD. © Copyright 2017 Physicians Postgraduate Press, Inc.