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.

Tumor necrosis factor-α inhibitor treatment and the risk of incident cardiovascular events in patients with early rheumatoid arthritis: a nested case-control study.

PubMed

Desai, Rishi J; Rao, Jaya K; Hansen, Richard A; Fang, Gang; Maciejewski, Matthew; Farley, Joel

2014-11-01

To compare the risk of cardiovascular (CV) events between use of tumor necrosis factor-α inhibitors (TNFi) and nonbiologic disease-modifying antirheumatic drugs (DMARD) in patients with early rheumatoid arthritis (RA). A nested case-control study was conducted using data from Truven's MarketScan commercial and Medicare claims database for patients with early RA who started treatment with either a TNFi or a nonbiologic DMARD between January 1, 2008, and December 31, 2010. Date of CV event diagnosis for cases was defined as the event date, and 12 age-matched and sex-matched controls were sampled using incidence density sampling. Drug exposure was defined into the following mutually exclusive categories hierarchically: (1) current use of TNFi (with or without nonbiologics), (2) past use of TNFi (with or without nonbiologics), (3) current use of nonbiologics only, and (4) past use of nonbiologics only. Current use was defined as any use in the period 90 days prior to the event date. Conditional logistic regression models were used to derive incidence rate ratios (IRR). From the cohort of patients with early RA, 279 cases of incident CV events and 3348 matched controls were identified. The adjusted risk of CV events was not significantly different between current TNFi users and current nonbiologic users (IRR 0.92, 95% CI 0.59-1.44). However, past users of nonbiologics showed significantly higher risk compared to current nonbiologic users (IRR 1.47, 95% CI 1.04-2.08). No differences in the CV risk were found between current TNFi and current nonbiologic DMARD treatment in patients with early RA.

Psychiatric comorbidity may not predict suicide during and after hospitalization. A nested case-control study with blinded raters.

PubMed

Walby, Fredrik A; Odegaard, Erik; Mehlum, Lars

2006-06-01

To investigate the differential impact of DSM-IV axis-I and axis-II disorders on completed suicide and to study if psychiatric comorbidity increases the risk of suicide in currently and previously hospitalized psychiatric patients. A nested case-control design based on case notes from 136 suicides and 166 matched controls. All cases and controls were rediagnosed using the SCID-CV for axis-I and the DSM-IV criteria for axis-II disorders and the inter-rater reliability was satisfactory. Raters were blind to the case and control status and the original hospital diagnoses. Depressive disorders and bipolar disorders were associated with an increased risk of suicide. No such effect was found for comorbidity between axis-I disorders and for comorbidity between axis-I and axis-II disorders. Psychiatric diagnoses, although made using a structured and criteria-based approach, was based on information recorded in case notes. Axis-II comorbidity could only be investigated at an aggregated level. Psychiatric comorbidity did not predict suicide in this sample. Mood disorders did, however, increase the risk significantly independent of history of previous suicide attempts. Both findings can inform identification and treatment of patients at high risk for completed suicide.

H. pylori seroprevalence and risk of diabetes: An ancillary case-control study nested in the diabetes prevention program.

PubMed

Alzahrani, Saud; Nelson, Jason; Moss, Steven F; Paulus, Jessica K; Knowler, William C; Pittas, Anastassios G

2017-10-01

To determine the association between H. pylori infection and risk of incident diabetes in adults at high risk for diabetes who participated in the Diabetes Prevention Program (DPP) study. In a nested case-control study conducted among 421 adults with newly diagnosed diabetes and 421 matched controls, we examined the association between serological status of H. pylori at baseline and risk of incident diabetes over a mean follow-up period of 2.6years. Using data from the baseline visit of the DPP, we also examined the cross-sectional association between presence of H. pylori antibodies and insulin sensitivity, insulin secretion and the disposition index-like measure after a 75-g oral glucose tolerance test (OGTT). At baseline, H. pylori antibodies were present in 40% of participants who developed diabetes and 39% of controls. After adjusting for matching factors, there was no association between exposure to H. pylori and incident diabetes (odds ratio [OR] of 1.04 (95% CI, 0.77 to 1.40). In cross-sectional analyses, H. pylori status was not significantly associated with insulin sensitivity and disposition index-like measure from OGTT. In adults at high risk for diabetes, H. pylori seropositivity was not associated with risk of developing diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

Feasibility of reusing time-matched controls in an overlapping cohort.

PubMed

Delcoigne, Bénédicte; Hagenbuch, Niels; Schelin, Maria Ec; Salim, Agus; Lindström, Linda S; Bergh, Jonas; Czene, Kamila; Reilly, Marie

2018-06-01

The methods developed for secondary analysis of nested case-control data have been illustrated only in simplified settings in a common cohort and have not found their way into biostatistical practice. This paper demonstrates the feasibility of reusing prior nested case-control data in a realistic setting where a new outcome is available in an overlapping cohort where no new controls were gathered and where all data have been anonymised. Using basic information about the background cohort and sampling criteria, the new cases and prior data are "aligned" to identify the common underlying study base. With this study base, a Kaplan-Meier table of the prior outcome extracts the risk sets required to calculate the weights to assign to the controls to remove the sampling bias. A weighted Cox regression, implemented in standard statistical software, provides unbiased hazard ratios. Using the method to compare cases of contralateral breast cancer to available controls from a prior study of metastases, we identified a multifocal tumor as a risk factor that has not been reported previously. We examine the sensitivity of the method to an imperfect weighting scheme and discuss its merits and pitfalls to provide guidance for its use in medical research studies.

Actinic keratosis-related signs predictive of squamous cell carcinoma in renal transplant recipients: a nested case-control study.

PubMed

Jiyad, Z; O'Rourke, P; Soyer, H P; Green, A C

2017-04-01

Squamous cell carcinoma (SCC) and intraepidermal carcinoma (IEC) commonly arise in actinically damaged skin. To identify clinical features of actinic change that correlate with an increased risk of SCC or IEC in the short-to-medium term as guidance for prioritizing field treatment. In a nested case-control study, cases were renal transplant recipients who developed an incident SCC or IEC within 18 months following baseline examination and photography. Controls without SCC or IEC were matched to cases on age, sex and duration of immunosuppression. Predefined skin sites on the head, neck and upper limbs were examined using baseline photographs to assess objectively the following features of actinic damage: presence of actinic keratosis (AK) patch (defined as AK > 1 cm 2 ), number of AK patches, number of AKs and area affected by AK. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using McNemar's test to identify differences in SCC/IEC risk combined and SCC risk alone between case and control skin sites. Thirty-nine cases were matched to 39 controls. Significant associations with the presence of an AK patch, number of AK patches, number of AKs and area affected by AKs were identified. The presence of an AK patch conferred an 18-fold increased risk of SCC (OR 18·00, 95% CI 2·84-750) and more than a sixfold increased risk of SCC/IEC combined (OR 6·60, 95% CI 2·56-21·66). AK patches are predictive of SCC/IEC development within 18 months. This can be used to guide site selection for field treatment in patients with widespread actinic damage. © 2016 British Association of Dermatologists.

Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study.

PubMed

McCourt, C; Coleman, H G; Murray, L J; Cantwell, M M; Dolan, O; Powe, D G; Cardwell, C R

2014-04-01

Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers. To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma. Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case-control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing. Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68-1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56-1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality. Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study. © 2014 British Association of Dermatologists.

Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs: a nested case-control study

PubMed Central

Vonkeman, Harald E; Fernandes, Robert W; van der Palen, Job; van Roon, Eric N; van de Laar, Mart AFJ

2007-01-01

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven. Selective cyclooxygenase-2 (COX-2) inhibitors reduce the risk for ulcer complications, but not completely in high-risk patients. This study determines which patients are especially at risk for NSAID ulcer complications and investigates the effectiveness of different preventive strategies in daily clinical practice. With the use of a nested case-control design, a large cohort of NSAID users was followed for 26 months. Cases were patients with NSAID ulcer complications necessitating hospitalisation; matched controls were selected from the remaining cohort of NSAID users who did not have NSAID ulcer complications. During the observational period, 104 incident cases were identified from a cohort of 51,903 NSAID users with 10,402 patient years of NSAID exposure (incidence 1% per year of NSAID use, age at diagnosis 70.4 ± 16.7 years (mean ± SD), 55.8% women), and 284 matched controls. Cases were characterised by serious, especially cardiovascular, co-morbidity. In-hospital mortality associated with NSAID ulcer complications was 10.6% (incidence 21.2 per 100,000 NSAID users). Concomitant proton-pump inhibitors (but not selective COX-2 inhibitors) were associated with a reduced risk for NSAID ulcer complications (the adjusted odds ratio 0.33; 95% confidence interval 0.17 to 0.67; p = 0.002). Especially at risk for NSAID ulcer complications are elderly patients with cardiovascular co-morbidity. Proton-pump inhibitors are associated with a reduced risk for NSAID ulcer complications. PMID:17521422

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

PubMed

Jobski, Kathrin; Behr, Sigrid; Garbe, Edeltraut

2011-09-01

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

Freshman year mental health symptoms and level of adaptation as predictors of Internet addiction: a retrospective nested case-control study of male Chinese college students.

PubMed

Yao, Bin; Han, Wei; Zeng, Lingxia; Guo, Xiong

2013-12-15

A retrospective nested case-control study was designed to explore whether freshman year mental health status and level of adaptation are predictors of Internet addiction. The study cohort was 977 college students at a university in northwest China. In the first college year, the students' mental health status and adaptation level were assessed using the Chinese College Student Mental Health Scale (CCSMHS) and the Chinese College Student Adjustment Scale (CCSAS). In the following 1-3 years, 62 Internet-addicted subjects were identified using Young's 8-item diagnostic questionnaire. Controls were matched for demographic characteristics. Using logistic regression analysis, freshman year mental health status, including factors such as somatization, anxiety, depression and self-contempt, and freshman year adaptive problems were found to be causal factors and predictors of Internet addiction. Freshman with features of depression, learning maladaptation and dissatisfaction could be an important target-intervention population for reducing Internet addiction. © 2013 Elsevier Ireland Ltd. All rights reserved.

Heart Disease, Hypertension, Gestational Diabetes Mellitus, and Preeclampsia/Eclampsia in Mothers With Juvenile Arthritis: A Nested Case-Control Study.

PubMed

Feldman, Debbie E; Vinet, Évelyne; Bérard, Anick; Duffy, Ciarán; Hazel, Beth; Meshefedjian, Garbis; Sylvestre, Marie-Pierre; Bernatsky, Sasha

2017-02-01

To determine whether women with a history of juvenile arthritis are at higher risk for heart disease and hypertension and for developing adverse maternal outcomes: gestational diabetes mellitus, maternal hypertension, and preeclampsia/eclampsia. We designed a nested case-control study from a cohort of first-time mothers with prior physician billing codes suggesting juvenile arthritis, and a matched comparison group without juvenile arthritis. For the nested case-control design, we selected 3 controls for each case for the outcomes of heart disease (n = 403), prepregnancy hypertension (n = 66), gestational diabetes mellitus (n = 285), maternal hypertension (n = 561), and preeclampsia/eclampsia (n = 236). We used conditional logistic regression, adjusting for maternal age and education. Having juvenile arthritis was associated with heart disease (odds ratio [OR] 2.44 [95% confidence interval (95% CI) 1.15-5.15]) but not with gestational hypertension, diabetes mellitus, or preeclampsia/eclampsia. All 66 cases of prepregnancy hypertension had juvenile arthritis. Having prepregnancy hypertension was strongly associated with preeclampsia/eclampsia (OR 8.05 [95% CI 2.69-24.07]). Women with a history of juvenile arthritis had a higher risk of heart disease. This risk signals the potential importance of cardiac prevention strategies in juvenile arthritis. As this was a retrospective study, it was not possible to correct for some relevant potential confounders. Further studies should assess the impact of medications, disease severity, and other factors (e.g., obesity) on cardiac outcomes in juvenile arthritis. © 2016, American College of Rheumatology.

Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma

PubMed Central

Chang, Ellen T.; Ambinder, Richard F.; Lennette, Evelyne T.; Rubertone, Mark V.; Mann, Risa B.; Borowitz, Michael; Weir, Edward G.; Abbondanzo, Susan L.; Mueller, Nancy E.

2012-01-01

An altered anti–Epstein-Barr virus (EBV) serologic profile preceding diagnosis is associated with an increased risk of Hodgkin lymphoma. It is unknown whether this atypical pattern predicts Hodgkin lymphoma risk further subdivided by determination of EBV in tumor cells. A nested case-control study of 128 incident Hodgkin lymphoma cases and 368 matched controls from active-duty military personnel with archived serum in the US Department of Defense Serum Repository was conducted to determine whether a panel of anti-EBV antibody titers differed in EBV+ and EBV− Hodgkin lymphoma. Among 40 EBV+ Hodgkin lymphoma cases and matched controls, statistically significant increased risks were associated with elevated anti-EBV VCA IgG antibody titers (relative risk = 3.1; 95% confidence interval [CI], 1.1-8.7), and an anti–EBNA-1/anti–EBNA-2 antibody ratio ≤ 1.0 versus > 1.0 (relative risk = 4.7; 95% CI, 1.6-13.8). In contrast, no significant associations were found among 88 EBV− Hodgkin lymphoma cases relative to their matched controls. In case-case analysis, EBV+ disease was significantly associated with a low anti–EBNA-1/anti–EBNA-2 antibody ratio. This distinc-tive serologic response to EBV latent antigens, indicative of immune dysfunction in other clinical settings, is associated with an increased risk of developing EBV+ but not EBV− Hodgkin lymphoma. PMID:22972983

Effectiveness of the 10-Valent Pneumococcal Conjugate Vaccine (PCV-10) in Children in Chile: A Nested Case-Control Study Using Nationwide Pneumonia Morbidity and Mortality Surveillance Data

PubMed Central

Toscano, Cristiana M.; Alencar, Gizelton P.; Alvarez, Andrés; Valenzuela, Maria T.; Andrus, Jon; del Aguila, Roberto; Hormazábal, Juan C.; Araya, Pamela; Pidal, Paola; Matus, Cuauhtemoc R.; de Oliveira, Lucia H.

2016-01-01

Background The ten-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Chilean National Immunization Program (NIP) in January 2011 with a 3+1 schedule (2, 4, 6 and 12 months) without catch-up vaccination. We evaluated the effectiveness of PCV10 on pneumonia morbidity and mortality among infants during the first two years after vaccine introduction. Methods This is a population-based nested case-control study using four merged nationwide case-based electronic health data registries: live birth, vaccination, hospitalization and mortality. Children born in 2010 and 2011 were followed from two moths of age for a period of two years. Using four different case definitions of pneumonia hospitalization and/or mortality (all-cause and pneumonia related deaths), all cases and four randomly selected matched controls per case were selected. Controls were matched to cases on analysis time. Vaccination status was then assessed. Vaccine effectiveness (VE) was estimated using conditional logistic regression. Results There were a total of 497,996 children in the 2010 and 2011 Chilean live-birth cohorts. PCV10 VE was 11.2% (95%CI 8.5–13.6) when all pneumonia hospitalizations and deaths were used to define cases. VE increased to 20.7 (95%CI 17.3–23.8) when ICD10 codes used to denote viral pneumonia were excluded from the case definition. VE estimates on pneumonia deaths and all-cause deaths were 71.5 (95%CI 9.0–91.8) and 34.8 (95% CI 23.7–44.4), respectively. Conclusion PCV10 vaccination substantially reduced the number of hospitalizations due to pneumonia and deaths due to pneumonia and to all-causes over this study period. Our findings also reinforce the importance of having quality health information systems for measuring VE. PMID:27058873

Association between biomass fuel and pulmonary tuberculosis: a nested case-control study.

PubMed

Kolappan, C; Subramani, R

2009-08-01

To quantify the association between biomass fuel usage and sputum-positive pulmonary tuberculosis. A tuberculosis prevalence survey was conducted in a random sample of 50 rural units (villages) and three urban units in the Tiruvallur district of Tamilnadu, India during the period 2001-2003. Additional data regarding exposure to tobacco smoking, alcohol consumption, biomass fuel usage and Standard of Living Index (SLI) were also collected from the study participants. A nested case-control study was carried out in this population. Cases are defined as bacteriological-positive cases diagnosed by either sputum smear or culture examination. For each case, five age- (within +/-5 years of age) and sex-matched controls were selected randomly from the non-cases residing in the same village/unit. Thus, 255 cases and 1275 controls were included in this study. The unadjusted OR measured from univariate analysis for biomass fuel is 2.9 (95% CI 1.8 to 4.7). The adjusted OR measured from multivariate analysis using Cox regression is 1.7 (95% CI 1.0 to 2.9). Thirty-six percent of cases are attributable to biomass fuel usage. The findings from this case-control study add to the evidence for an independent association between biomass smoke and pulmonary tuberculosis. Improvement in standards of living brought about by economic development will lead to more people using cleaner fuels for cooking than biomass fuel which in turn will lead to a reduction in the occurrence of pulmonary tuberculosis in the community.

Head or brain injuries and Alzheimer's disease: A nested case-control register study.

PubMed

Tolppanen, Anna-Maija; Taipale, Heidi; Hartikainen, Sirpa

2017-12-01

Many previous studies have been limited by self- or proxy-reported injury or short follow-up. We investigated whether head or brain injuries are associated with Alzheimer's disease (AD), possible modifying factors and dose-response relationship. Nested register-based case-control study of all community dwellers who received clinically verified AD diagnosis in Finland in 2005 to 2011 (n = 70,719) and one to four matched controls for each case (n of controls = 282,862). The magnitude of association between hospital-treated head and/or brain injuries was strongly dependent on the lag time between exposure and outcome. With a 5-year lag time, head injury (adjusted odds ratio; 95% confidence interval 1.19; 1.15-1.23) or brain injury (1.23; 1.18-1.29) was associated with higher risk of AD. Dose-response relationship with number and severity of injuries was observed. Associations were stronger in those with earlier onset of AD. Stronger associations with shorter lag times indicate that head and/or brain injuries may also reflect the ongoing AD disease process. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Pituitary Antibodies in Women with Hashimoto's Thyroiditis: Prevalence in Diagnostic and Prediagnostic Sera

PubMed Central

Guaraldi, Federica; Landek-Salgado, Melissa A.; Hutfless, Susan; Samoni, Francesca; Talor, Monica V.; Matos, Peter G.; Salvatori, Roberto; Rose, Noel R.

2012-01-01

Background Pituitary antibodies have been reported with greater frequency in patients with Hashimoto's thyroiditis than in healthy controls, although there is significant variability in the strength of the association and the methodologies used. Methods We designed a nested case–control study to characterize the prevalence of pituitary antibodies at the time of the clinical diagnosis of Hashimoto's thyroiditis, as well as at 2, 5, and 7 years before diagnosis. Active component female service member cases (n=87) and matched female controls (n=107) were selected using the Defense Medical Surveillance System database (DMSSD) between January 1998 and December 2007. Pituitary antibodies were measured by immunofluorescence using human pituitary glands collected at autopsy as the substrate. Results At diagnosis, pituitary antibodies were present in 9% of cases with Hashimoto's (8 of 87) and 3% of controls (3 of 107). When the data were analyzed using a conditional logistic regression model, which takes into account the matching on age and work status, pituitary antibodies increased the odds of having Hashimoto's thyroiditis by sevenfold (95% confidence interval from 1.3 to 40.1, p=0.028), after adjusting for components of the DMSSD-category-termed race and for thyroperoxidase antibodies. Before diagnosis, pituitary antibodies were positive in 3 of the 11 subjects (2 cases and 1 control) at the −2-year time point, and negative in all 11 subjects at the −5- and −7-year time points. Conclusions In summary, using a nested case–control design, we confirm that pituitary antibodies are more common in Hashimoto's thyroiditis and suggest that they appear late during its natural history. PMID:22468943

Exposure to sennoside-digoxin interaction and risk of digoxin toxicity: a population-based nested case-control study.

PubMed

Wang, Meng-Ting; Li, I-Hsun; Lee, Wan-Ju; Huang, Tien-Yu; Leu, Hsin-Bang; Chan, Agnes L F

2011-11-01

Digoxin is an important medication for heart failure (HF) patients and sennosides are widely used to treat constipation. Recently, safety concerns have been raised about a possible interaction between sennosides and digoxin, an issue that has not been studied empirically. This study therefore aimed to evaluate whether exposure to sennoside-digoxin interaction is associated with an increased risk of digoxin toxicity. This was a population-based nested case-control study that analysed data obtained from the Taiwan National Health Insurance Research Database between 1 January 2001 and 31 December 2004. All HF patients treated with digoxin for the first time were included as the study cohort. Of these, cases were identified as subjects hospitalized for digoxin toxicity (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM 972.1), and matched to randomly selected controls. Use of sennosides was compared between the two groups. Odds ratios (ORs) were employed to quantify the risk associated with exposure to sennoside-digoxin interaction by conditional logistic regression. The study cohort comprised 222,527 HF patients, of whom 524 were identified as cases and 2,502 as matched controls. Use of sennosides during the 14 days preceding the index date was found to be associated with a 1.61-fold increased risk of digoxin toxicity [95% confidence interval (CI) = 1.15, 2.25]. Additionally, a greater risk was observed for sennosides prescribed at an average daily dose ≥ 24 mg (adjusted OR = 1.93; 95% CI = 1.27, 2.94). The combined use of sennosides and digoxin was found to be associated with a modest increased risk of digoxin toxicity in HF patients.

A prospective study of Trichomonas vaginalis and prostate cancer risk among African American men.

PubMed

Fowke, Jay H; Han, Xijing; Alderete, J F; Moses, Kelvin A; Signorello, Lisa B; Blot, William J

2016-04-18

African Americans (AA) have a higher prevalence of Trichomonas vaginalis (Tv) infection and a higher prostate (PC) risk. Past studies suggest an association between Tv seropositivity and PC, and therefore we prospectively investigated this association among AA men. Incident PC cases were individually matched to controls in a nested case-control study within the Southern Community Cohort Study (SCCS). Primary analysis included 296 PC cases and 497 race-matched controls. Levels of Tv antibody response were measured by ELISA in serum collected at baseline. Tv antibody response did not significantly differ between cases and controls overall or within AA participants (253 AA cases). There were no significant associations or trends between levels of Tv response and PC risk or the diagnosis of aggressive PC. We found no evidence of a prospective association between baseline Tv infection and PC risk in AA men. Tv infection in men may have substantial health implications in HIV transmission and reproductive outcomes, but may not impact future PC risk in AA men at high-risk for PC. Further efforts need to define past vs. present Tv infection and to separate pathophysiology from PC detection.

Methodologic considerations in the design and analysis of nested case-control studies: association between cytokines and postoperative delirium.

PubMed

Ngo, Long H; Inouye, Sharon K; Jones, Richard N; Travison, Thomas G; Libermann, Towia A; Dillon, Simon T; Kuchel, George A; Vasunilashorn, Sarinnapha M; Alsop, David C; Marcantonio, Edward R

2017-06-06

The nested case-control study (NCC) design within a prospective cohort study is used when outcome data are available for all subjects, but the exposure of interest has not been collected, and is difficult or prohibitively expensive to obtain for all subjects. A NCC analysis with good matching procedures yields estimates that are as efficient and unbiased as estimates from the full cohort study. We present methodological considerations in a matched NCC design and analysis, which include the choice of match algorithms, analysis methods to evaluate the association of exposures of interest with outcomes, and consideration of overmatching. Matched, NCC design within a longitudinal observational prospective cohort study in the setting of two academic hospitals. Study participants are patients aged over 70 years who underwent scheduled major non-cardiac surgery. The primary outcome was postoperative delirium from in-hospital interviews and medical record review. The main exposure was IL-6 concentration (pg/ml) from blood sampled at three time points before delirium occurred. We used nonparametric signed ranked test to test for the median of the paired differences. We used conditional logistic regression to model the risk of IL-6 on delirium incidence. Simulation was used to generate a sample of cohort data on which unconditional multivariable logistic regression was used, and the results were compared to those of the conditional logistic regression. Partial R-square was used to assess the level of overmatching. We found that the optimal match algorithm yielded more matched pairs than the greedy algorithm. The choice of analytic strategy-whether to consider measured cytokine levels as the predictor or outcome-- yielded inferences that have different clinical interpretations but similar levels of statistical significance. Estimation results from NCC design using conditional logistic regression, and from simulated cohort design using unconditional logistic regression, were similar. We found minimal evidence for overmatching. Using a matched NCC approach introduces methodological challenges into the study design and data analysis. Nonetheless, with careful selection of the match algorithm, match factors, and analysis methods, this design is cost effective and, for our study, yields estimates that are similar to those from a prospective cohort study design.

Primary health care utilization prior to suicide: a retrospective case-control study among active-duty military personnel.

PubMed

Hochman, Eldar; Shelef, Leah; Mann, J John; Portugese, Shirly; Krivoy, Amir; Shoval, Gal; Weiser, Mark; Fruchter, Eyal

2014-08-01

About 45% of civilians who died by suicide had contact with a doctor within 1 month of death. Thus, educating primary care physicians (PCP) to detect and mitigate depression is an important suicide-prevention strategy. However, the PCP consulting rate before suicide has not been examined in a military population. We investigated the utilization of primary health care and mental health services by active-duty military personnel suicide cases prior to death in comparison to matched military controls. All suicides (N = 170) were extracted from a cohort of all active-duty Israeli military male personnel between 2002 and 2012. Applying a retrospective, nested case-control design, we compared primary care services utilization by suicide cases with demographic and occupationally matched military controls (N = 500). Whereas 38.3% of suicide cases contacted a PCP within the last month before death, only 27.6% of suicide cases contacted a mental health specialist during their entire service time. The PCP contact rate within 1 month before death or index day did not differ between suicide cases and military controls (38.3% vs. 33.8%, χ²₁ = 1.05, P = .3). More suicide cases contacted a mental health specialist within service time than did military controls (27.6% vs. 13.6%, χ²₁ = 10.85, P = .001). Even though PCP contact rate by military personnel who died by suicide is slightly lower than that reported for civilians who died by suicide prior to their death, it is higher than mental health specialist contact rate and higher than that by age-matched civilians who died by suicide. These results imply that PCPs education is a viable approach to suicide prevention in a military setting. © Copyright 2014 Physicians Postgraduate Press, Inc.

Predictors and outcomes of superior mesenteric artery syndrome in patients with constipation: a prospective, nested case-control study.

PubMed

Xu, Lin; Yu, Wen-Kui; Lin, Zhi-Liang; Jiang, Jun; Feng, Xiao-Bo; Li, Ning

2014-10-01

Superior mesenteric artery (SMA) syndrome may occur in patients with constipation, whereas the association between these two distinct diseases has not been confirmed yet. We investigated the incidence, risk factors and treatment strategy associated with SMA syndrome in constipated patients. We conducted a prospective nested case-control study from a 9-year hospitalization cohort (n=973). Cases were matched to controls 1:4 on factors of age and gender. Cases developed SMA syndrome in long term follow-up (n=26) and controls did not (n=104). Independent risk factors were identified by using univariate analysis and conditional logistic regression analysis. Enteral nutritional support was applied in all cases and its curative effect was evaluated by retrospective analysis. The incidence of SMA syndrome was 2.67%. The risk factors under scrutiny were body mass index (BMI)≤18 (odds ratio (OR) 2.89, 95% CI 1.14 to 9.31) and abnormal colon transit time (OR 3.57, 95% CI 1.36 to 9.35). Twenty-two patients recovered after treatment of nutritional support, and the success rate of conservative treatment was 84.6%. BMI≤18 and prolonged colon transit time both were risk factors associated with SMA syndrome in constipated patients. Enteral nutritional support should be adopted as the first-line treatment for this condition.

Correlation of CpG Island Methylation of the Cytochrome P450 2E1/2D6 Genes with Liver Injury Induced by Anti-Tuberculosis Drugs: A Nested Case-Control Study.

PubMed

Zhang, Jinling; Zhu, Xuebin; Li, Yuhong; Zhu, Lingyan; Li, Shiming; Zheng, Guoying; Ren, Qi; Xiao, Yonghong; Feng, Fumin

2016-08-01

This study investigated the role of CpG island methylation of the CYP2E1 and CYP2D6 genes in liver injury induced by anti-TB drugs from an epigenetic perspective in a Chinese cohort. A 1:1 matched nested case-control study design was applied. Pulmonary tuberculosis (TB) patients, who underwent standard anti-TB therapy and developed liver injury were defined as cases, while those who did not develop liver injury were defined as control. The two groups were matched in terms of sex, treatment regimen, and age. In 114 pairs of cases, CpG island methylation levels of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA were found to be significantly correlated with the occurrence of anti-TB drug-induced liver injury (ADLI), with odds ratio (OR) values of 2.429 and 3.500, respectively (p < 0.01). Moreover, through multivariate logistic regression analysis, CpG island methylation of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA were found to be significantly correlated with the occurrence of ADLI, with adjusted OR values of 4.390 (95% confidence interval (CI): 1.982-9.724) and 9.193 (95% CI: 3.624-25.888), respectively (p < 0.001). These results suggest that aberrantly elevated methylation of CpG islands of the CYP2E1 and CYP2D6 genes in plasma cell-free DNA may increase the risk of ADLI in Chinese TB patients.

Using the entire history in the analysis of nested case cohort samples.

PubMed

Rivera, C L; Lumley, T

2016-08-15

Countermatching designs can provide more efficient estimates than simple matching or case-cohort designs in certain situations such as when good surrogate variables for an exposure of interest are available. We extend pseudolikelihood estimation for the Cox model under countermatching designs to models where time-varying covariates are considered. We also implement pseudolikelihood with calibrated weights to improve efficiency in nested case-control designs in the presence of time-varying variables. A simulation study is carried out, which considers four different scenarios including a binary time-dependent variable, a continuous time-dependent variable, and the case including interactions in each. Simulation results show that pseudolikelihood with calibrated weights under countermatching offers large gains in efficiency if compared to case-cohort. Pseudolikelihood with calibrated weights yielded more efficient estimators than pseudolikelihood estimators. Additionally, estimators were more efficient under countermatching than under case-cohort for the situations considered. The methods are illustrated using the Colorado Plateau uranium miners cohort. Furthermore, we present a general method to generate survival times with time-varying covariates. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Duration of exposure to multiple antibiotics is associated with increased risk of VRE bacteraemia: a nested case-control study.

PubMed

Gouliouris, Theodore; Warne, Ben; Cartwright, Edward J P; Bedford, Luke; Weerasuriya, Chathika K; Raven, Kathy E; Brown, Nick M; Török, M Estée; Limmathurotsakul, Direk; Peacock, Sharon J

2018-03-13

VRE bacteraemia has a high mortality and continues to defy control. Antibiotic risk factors for VRE bacteraemia have not been adequately defined. We aimed to determine the risk factors for VRE bacteraemia focusing on duration of antibiotic exposure. A retrospective matched nested case-control study was conducted amongst hospitalized patients at Cambridge University Hospitals NHS Foundation Trust (CUH) from 1 January 2006 to 31 December 2012. Cases who developed a first episode of VRE bacteraemia were matched 1:1 to controls by length of stay, year, specialty and ward type. Independent risk factors for VRE bacteraemia were evaluated using conditional logistic regression. Two hundred and thirty-five cases were compared with 220 controls. Duration of exposure to parenteral vancomycin, fluoroquinolones and meropenem was independently associated with VRE bacteraemia. Compared with patients with no exposure to vancomycin, those who received courses of 1-3 days, 4-7 days or >7 days had a stepwise increase in risk of VRE bacteraemia [conditional OR (cOR) 1.2 (95% CI 0.4-3.8), 3.8 (95% CI 1.2-11.7) and 6.6 (95% CI 1.9-22.8), respectively]. Other risk factors were: presence of a central venous catheter (CVC) [cOR 8.7 (95% CI 2.6-29.5)]; neutropenia [cOR 15.5 (95% CI 4.2-57.0)]; hypoalbuminaemia [cOR 8.5 (95% CI 2.4-29.5)]; malignancy [cOR 4.4 (95% CI 1.6-12.0)]; gastrointestinal disease [cOR 12.4 (95% CI 4.2-36.8)]; and hepatobiliary disease [cOR 7.9 (95% CI 2.1-29.9)]. Longer exposure to vancomycin, fluoroquinolones or meropenem was associated with VRE bacteraemia. Antimicrobial stewardship interventions targeting high-risk antibiotics are required to complement infection control procedures against VRE bacteraemia.

Maternal Infection during Pregnancy and Autism Spectrum Disorders

PubMed Central

Zerbo, Ousseny; Qian, Yinge; Yoshida, Cathleen; Grether, Judith K.; Van de Water, Judy; Croen, Lisa A.

2014-01-01

We conducted a nested case-control study including 407 cases and 2075 frequency matched controls to investigate the association between maternal infections during pregnancy and risk of autism spectrum disorders (ASD). Cases, controls, and maternal infections were ascertained from Kaiser Permanente Northern California clinical databases. No overall association between diagnoses of any maternal infection during pregnancy and ASD (adjusted odds ratio [ORadj] = 1.15, 95% confidence interval [CI] 0.92 – 1.43). However, women with infections diagnosed during a hospital admission (ORadj= 1.48, 95% CI1.07 – 2.04), particularly bacterial infections (ORadj = 1.58, 95% CI 1.06 – 2.37), were at increased risk of delivering a child with ASD. Multiple infections during pregnancy were associated with ASD (ORadj = 1.36, 95% CI 1.05 – 1.78). PMID:24366406

Air Pollution and Pulmonary Tuberculosis: A Nested Case-Control Study among Members of a Northern California Health Plan.

PubMed

Smith, Geneé S; Van Den Eeden, Stephen K; Garcia, Cynthia; Shan, Jun; Baxter, Roger; Herring, Amy H; Richardson, David B; Van Rie, Annelies; Emch, Michael; Gammon, Marilie D

2016-06-01

Ecologic analyses, case-case comparisons, and animal experiments suggest positive associations between air pollution and tuberculosis. We evaluated this hypothesis in a large sample, which yielded results that are applicable to the general population. We conducted a case-control study nested within a cohort of Kaiser Permanente of Northern California members. All active pulmonary tuberculosis (TB) cases newly diagnosed between 1996 and 2010 (n = 2,309) were matched to two controls (n = 4,604) by age, sex, and race/ethnicity on the index date corresponding with the case diagnosis date. Average individual-level concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) and 10 μm (PM10) for 2 years before diagnosis/entry into the study were estimated using measurements from the California Air Resources Board monitor closest to the participant's residence. In single-pollutant adjusted conditional logistic regression models, the pulmonary TB odds ratios (95% confidence intervals) for the highest quintile (vs. lowest) were 1.50 (95% CI: 1.15, 1.95) for CO and 1.42 (95% CI: 1.10, 1.84) for NO2. Corresponding estimates were higher among never [1.68 (95% CI: 1.26, 2.24)] than ever [1.19 (95% CI: 0.74, 1.92)] smokers for CO. In contrast, for NO2, estimates were higher among ever [1.81 (95% CI: 1.13, 2.91)] than never [1.29 (95% CI: 0.97, 1.71)] smokers. O3 was inversely associated for smokers [0.66 (95% CI: 0.43, 1.02)] and never smokers [0.65 (95% CI: 0.52, 0.81)]. No other consistent patterns were observed. In this first, to our knowledge, U.S. nested case-control study on air pollution and pulmonary TB, we observed positive associations with ambient CO and NO2, which require confirmation. Smith GS, Van Den Eeden SK, Garcia C, Shan J, Baxter R, Herring AH, Richardson DB, Van Rie A, Emch M, Gammon MD. 2016. Air pollution and pulmonary tuberculosis: a nested case-control study among members of a Northern California health plan. Environ Health Perspect 124:761-768; http://dx.doi.org/10.1289/ehp.1408166.

Ticagrelor and bradycardia: a nested case-control study.

PubMed

Turgeon, Ricky D; Fernandes, Kimberly A; Juurlink, David; Tu, Jack V; Mamdani, Muhammad

2015-12-01

Ticagrelor increases serum adenosine concentrations, slowing conduction and possibly leading to bradycardia. Clinical trial data have shown numerically, though not statistically significantly, higher rates of bradyarrhythmias with ticagrelor versus clopidogrel. Additionally, recent case reports have further raised concerns for this adverse effect. We explored the association between ticagrelor and hospitalization for bradycardia in a real-world setting. We conducted a population-based, nested case-control study of Ontario residents, 66 years of age or older, discharged after a first acute coronary syndrome by linking multiple healthcare databases. Cases included patients hospitalized for bradycardia within 1 year of starting a P2Y12 inhibitor. For each case, we identified 4 controls matched on age, sex, index date, and current use of a P2Y12 inhibitor. The exposure of interest was a prescription for ticagrelor within 90 days, with clopidogrel use as the reference group. From April 2012 to March 2014, we identified 140 cases and 560 controls who met the study criteria. We found no significant association between bradycardia and exposure to ticagrelor relative to clopidogrel in the previous 90 days prior to the index date (adjusted odds ratio 1.06, 95% confidence interval 0.65-2.21). Further adjustment for potential confounders also did not identify a significant association. Among older patients with a first acute coronary syndrome, use of ticagrelor was not associated with a greater risk of admission for bradycardia relative to clopidogrel. Copyright © 2015 John Wiley & Sons, Ltd.

Leukemia and brain tumors in Norwegian railway workers, a nested case-control study.

PubMed

Tynes, T; Jynge, H; Vistnes, A I

1994-04-01

In an attempt to assess whether exposure to electromagnetic fields on Norwegian railways induces brain tumors or leukemia, the authors conducted a nested case-control study of railway workers based on incident cases from the Cancer Registry of Norway in a cohort of 13,030 male Norwegian railway workers who had worked on either electric or non-electric railways. The cohort comprised railway line, outdoor station, and electricity workers. The case series comprised 39 men with brain tumors and 52 men with leukemia (follow-up, 1958-1990). Each case was matched on age with four or five controls selected from the same cohort. The exposure of each study subject to electric and magnetic fields was evaluated from cumulative exposure measures based on present measurements and historical data. Limited information on potential confounders such as creosote, solvents, and herbicides was also collected; information on whether the subject had smoked was obtained by interviews with the subjects or work colleagues. The case-control analysis showed that men employed on electric railways, compared with non-electric ones, had an odds ratio for leukemia of 0.70 (adjusted for smoking) and an odds ratio for brain tumor of 0.87. No significant trend was shown for exposure to either magnetic or electric fields. These results do not support an association between exposure to 16 2/3-Hertz electric or magnetic fields and the risk for leukemia or brain tumors.

Chromium Exposure and Risk of Cardiovascular Disease in High Cardiovascular Risk Subjects　- Nested Case-Control Study in the Prevention With Mediterranean Diet (PREDIMED) Study.

PubMed

Gutiérrez-Bedmar, Mario; Martínez-González, Miguel Ángel; Muñoz-Bravo, Carlos; Ruiz-Canela, Miguel; Mariscal, Alberto; Salas-Salvadó, Jordi; Estruch, Ramón; Corella, Dolores; Arós, Fernando; Fito, Monserrat; Lapetra, José; Serra-Majem, Lluís; Pintó, Xavier; Alonso-Gómez, Ángel; Portoles, Olga; Fiol, Miquel; Bulló, Mónica; Castañer, Olga; Ros, Emilio; Gómez-Gracia, Enrique

2017-07-25

Epidemiological data on chromium (Cr) exposure and the risk of cardiovascular disease (CVD) are still limited. Toenail Cr level (TCL) provides a time-integrated measure reflecting long-term Cr exposure. We measured TCL to assess the hypothesis that long-term Cr exposure was inversely associated with incident CVD in a population at high risk for CVD.Methods and Results:The associations between TCL and CVD were evaluated in a case-control study nested within the "PREvención con DIeta MEDiterránea" (PREDIMED) trial. We randomly selected 147 of the 288 patients diagnosed with CVD during follow-up and matched them on age and sex to 271 controls. Instrumental neutron activation analysis was used to assess TCL. In-person interviews, medical record reviews, and validated questionnaires were used to assess covariates. The fully adjusted OR for the highest vs. lowest quartile of toenail Cr was 0.54 (95% CI: 0.26-1.14; P trend =0.189) for the nested case-control study. On stratification for diabetes mellitus (DM), OR was 1.37 (95% CI: 0.54-3.46; P trend =0.364) for the DM group, and 0.25 (95% CI: 0.08-0.80; P trend =0.030) for the non-DM group (P for interaction=0.078). The present findings, although not statistically significant, are consistent with previously reported inverse associations between TCL and CVD. These results, especially for non-DM patients, increase the limited epidemiological knowledge about the possible protective role of Cr against CVD. (Trial registration: www.controlled-trials.com; ISRCTN35739639.).

Non-tuberculous mycobacterial bloodstream infections in patients with indwelling vascular catheters - the role of sickle cell anaemia.

PubMed

Edun, Babatunde; Shah, Ansal; Durkin, Martin; Whitmire, Melanie; Williams, Shanetta Patterson; Albrecht, Helmut; Al-Hasan, Majdi; Weissman, Sharon

2017-05-01

Few studies have examined risk factors for nontuberculous mycobacteria (NTM) bloodstream infections (BSI) involving indwelling vascular catheters (IDVC). Sickle cell anaemia (HbSS/SC) is known to affect several aspects of the immune system leading to relative immune deficiency. The purpose of this retrospective nested case-control study was to determine if HbSS/SC is a risk factor for NTM BSI among individuals with IDVCs. All NTM IDVC infections (cases) at two tertiary hospitals from 2008 to 2014 were reviewed. Cases were matched 2:1 with controls who had IDVC infections due to organisms other than NTM. Matching criteria included age within 10 years and IDVC infection within three months of index case. Logistic regression was used to identify risk factors for IDVC infection due to NTM. Nineteen NTM BSIs were identified. Three cases were excluded because they did not have IDVCs at the time their BSI was identified. Sixteen cases of NTM IDVC infection were matched to 32 controls with IDVC infections due to other organisms. The mean age of patients with IDVC infections was 48.5 years and 28 (58%) were male. Compared to the control group those with NTM BSI were more likely to have HbSS/SC 38% (6/16) versus 6% (2/32) (p = .006). IDVCs are a risk factor for NTM BSI. Sickle cell anaemia appears to be a risk factor for IDVC infections due to NTM. This study is limited by the small sample size. A larger study is needed to further investigate the association between HbSS/SC and NTM IDVC infections.

Sarcoidosis diagnosed after September 11, 2001, among adults exposed to the World Trade Center disaster.

PubMed

Jordan, Hannah T; Stellman, Steven D; Prezant, David; Teirstein, Alvin; Osahan, Sukhminder S; Cone, James E

2011-09-01

Explore relationships between World Trade Center (WTC) exposures and sarcoidosis. Sarcoidosis has been reported after exposure to the WTC disaster. We ascertained biopsy-proven post-9/11 sarcoidosis among WTC Health Registry enrollees. Cases diagnosed after Registry enrollment were included in a nested case-control study. Controls were matched to cases on age, sex, race or ethnicity, and eligibility group (eg, rescue or recovery worker). We identified 43 cases of post-9/11 sarcoidosis. Twenty-eight incident cases and 109 controls were included in the case-control analysis. Working on the WTC debris pile was associated with sarcoidosis (odds ratio 9.1, 95% confidence interval 1.1 to 74.0), but WTC dust cloud exposure was not (odds ratio 1.0, 95% confidence interval 0.4 to 2.8). Working on the WTC debris pile was associated with an elevated risk of post-9/11 sarcoidosis. Occupationally exposed workers may be at increased risk. (C)2011The American College of Occupational and Environmental Medicine

Helicobacter pylori infection, chronic corpus atrophic gastritis and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: A nested case-control study.

PubMed

Huang, Jiaqi; Zagai, Ulrika; Hallmans, Göran; Nyrén, Olof; Engstrand, Lars; Stolzenberg-Solomon, Rachael; Duell, Eric J; Overvad, Kim; Katzke, Verena A; Kaaks, Rudolf; Jenab, Mazda; Park, Jin Young; Murillo, Raul; Trichopoulou, Antonia; Lagiou, Pagona; Bamia, Christina; Bradbury, Kathryn E; Riboli, Elio; Aune, Dagfinn; Tsilidis, Konstantinos K; Capellá, Gabriel; Agudo, Antonio; Krogh, Vittorio; Palli, Domenico; Panico, Salvatore; Weiderpass, Elisabete; Tjønneland, Anne; Olsen, Anja; Martínez, Begoña; Redondo-Sanchez, Daniel; Chirlaque, Maria-Dolores; Hm Peeters, Petra; Regnér, Sara; Lindkvist, Björn; Naccarati, Alessio; Ardanaz, Eva; Larrañaga, Nerea; Boutron-Ruault, Marie-Christine; Rebours, Vinciane; Barré, Amélie; Bueno-de-Mesquita, H B As; Ye, Weimin

2017-04-15

The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction < 0.01). Our findings provided evidence supporting the null association between H. pylori infection and pancreatic cancer risk in western European populations. However, the suggested association between chronic corpus atrophic gastritis and pancreatic cancer risk warrants independent verification in future studies, and, if confirmed, further studies on the underlying mechanisms. © 2016 UICC.

A nested case-control study of predictors for tuberculosis recurrence in a large UK Centre.

PubMed

Rosser, Andrew; Richardson, Matthew; Wiselka, Martin J; Free, Robert C; Woltmann, Gerrit; Mukamolova, Galina V; Pareek, Manish

2018-02-27

Tuberculosis (TB) recurrence represents a challenge to control programs. In low incidence countries, the prevailing risk factors leading to recurrence are poorly characterised. We conducted a nested case-control study using the Leicester TB service TBIT database. Cases were identified from database notifications between 1994 and 2014. Controls had one episode and were matched to cases on a ratio of two to one by the date of notification. Multiple imputation was used to account for missing data. Multivariate conditional logistic regression analysis was employed to identify clinical, sociodemographic and TB specific risk factors for recurrence. From a cohort of 4628 patients, 82 TB recurrences occurred (1.8%). Nineteen of 82 patients had paired isolates with MIRU-VNTR strain type profiles available, of which 84% were relapses and 16% reinfections. On multivariate analysis, smoking (OR 3.8; p = 0.04), grade 3/4 adverse drug reactions (OR 5.6; p = 0.02), ethnicity 'Indian subcontinent' (OR 8.5; p = <0.01), ethnicity 'other' (OR 31.2; p = 0.01) and receipt of immunosuppressants (OR 6.8; p = <0.01) were independent predictors of TB recurrence. Within this UK setting, the rate of TB recurrence was low, predominantly due to relapse. The identification of an elevated recurrence risk amongst the ethnic group contributing most cases to the national TB burden presents an opportunity to improve individual and population health.

Cumulative exposure to biologics and risk of cancer in psoriasis patients: A meta-analysis of Psonet studies from Israel, Italy, Spain, United Kingdom and Republic of Ireland.

PubMed

Garcia-Doval, I; Descalzo, M A; Mason, K J; Cohen, A D; Ormerod, A D; Gómez-García, F J; Cazzaniga, S; Feldhamer, I; Ali, H; Herrera-Acosta, E; Griffiths, C E M; Stern, R; Naldi, L

2018-05-03

Cancer risk following long-term exposure to systemic immunomodulatory therapies in psoriasis patients is possible. To assess a dose-response relationship between cumulative length of exposure to biologic therapy and risk of cancer. Four national studies (a healthcare database from Israel, and prospective cohorts form Italy, Spain and UK/ROI) collaborating through Psonet (European Registry of Psoriasis) participated in these nested case-control studies, including nearly 60.000 person-years of observation. Cases were patients who developed an incident cancer. Patients with previous cancers and benign or in-situ tumours were excluded. Four cancer-free controls were matched to each case on year of birth, gender, geographic area, and registration year. Follow-up for controls was censored at the date of cancer diagnosis for the matched case. Conditional logistic regression was performed by each registry. Results were pooled using random effects meta-analysis. 728 cases and 2671 controls were identified. After matching, differences between cases and controls were present for the Charlson comorbidity index in all three registries, and in the prevalence of previous exposure to psoralen-ultraviolet-A (PUVA) and smoking (BADBIR only). The risk of first cancers was not significantly associated with cumulative exposure to biologics (adjusted odds ratio per year of exposure 1.02; 95%CI 0.92, 1.13). Results were similar if squamous and basal cell carcinomas were included in the outcome. Cumulative length of exposure to biologic therapies of psoriasis patients in real-world clinical practice does not appear to be linked to a higher risk of cancer after several years of use. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Prospective study of blood metabolites associated with colorectal cancer risk.

PubMed

Shu, Xiang; Xiang, Yong-Bing; Rothman, Nathaniel; Yu, Danxia; Li, Hong-Lan; Yang, Gong; Cai, Hui; Ma, Xiao; Lan, Qing; Gao, Yu-Tang; Jia, Wei; Shu, Xiao-Ou; Zheng, Wei

2018-02-26

Few prospective studies, and none in Asians, have systematically evaluated the relationship between blood metabolites and colorectal cancer risk. We conducted a nested case-control study to search for risk-associated metabolite biomarkers for colorectal cancer in an Asian population using blood samples collected prior to cancer diagnosis. Conditional logistic regression was performed to assess associations of metabolites with cancer risk. In this study, we included 250 incident cases with colorectal cancer and individually matched controls nested within two prospective Shanghai cohorts. We found 35 metabolites associated with risk of colorectal cancer after adjusting for multiple comparisons. Among them, 12 metabolites were glycerophospholipids including nine associated with reduced risk of colorectal cancer and three with increased risk [odds ratios per standard deviation increase of transformed metabolites: 0.31-1.98; p values: 0.002-1.25 × 10 -10 ]. The other 23 metabolites associated with colorectal cancer risk included nine lipids other than glycerophospholipid, seven aromatic compounds, five organic acids and four other organic compounds. After mutual adjustment, nine metabolites remained statistically significant for colorectal cancer. Together, these independently associated metabolites can separate cancer cases from controls with an area under the curve of 0.76 for colorectal cancer. We have identified that dysregulation of glycerophospholipids may contribute to risk of colorectal cancer. © 2018 UICC.

Bioavailable serum estradiol may alter radiation risk of postmenopausal breast cancer: a nested case-control study.

PubMed

Grant, Eric J; Cologne, John B; Sharp, Gerald B; Eguchi, Hidetaka; Stevens, Richard G; Izumi, Shizue; Kim, Young-Min; Berrington de González, Amy; Ohishi, Waka; Nakachi, Kei

2018-02-01

Ionizing radiation and high levels of circulating estradiol are known breast cancer carcinogens. We investigated the risk of first primary postmenopausal breast cancer in relation to the combined effects of whole-body ionizing radiation exposure and prediagnostic levels of postmenopausal sex hormones, particularly bioavailable estradiol (bE 2 ). A nested case-control study of 57 incident breast cancer cases matched with 110 controls among atomic bomb survivors. Joint effects of breast radiation dose and circulating levels of sex hormones were assessed using binary regression and path analysis. Radiation exposure, higher levels of bE 2 , testosterone and progesterone, and established reproductive risk factors were positively associated with postmenopausal breast cancer risk. A test for mediation of the effect of radiation via bE 2 level suggested a small (14%) but significant mediation (p = 0.004). The estimated interaction between radiation and bE 2 was large but not significant (interaction = 3.86; p = 0.32). There is accumulating evidence that ionizing radiation not only damages DNA but also alters other organ systems. While caution is needed, some portion of the radiation risk of postmenopausal breast cancer appeared to be mediated through bE 2 levels, which may be evidence for cancer risks due to both direct and indirect effects of radiation.

Risk of acute coronary events associated with glyburide compared with gliclazide use in patients with type 2 diabetes: a nested case-control study.

PubMed

Abdelmoneim, A S; Eurich, D T; Gamble, J M; Johnson, J A; Seubert, J M; Qiu, W; Simpson, S H

2014-01-01

Sulfonylureas might increase the risk of adverse cardiovascular events; however, emerging evidence suggests there may be important differences amongst these drugs. Some, like glyburide, inhibit KATP channels in the heart and pancreas, while others, like gliclazide, are more likely to selectively inhibit KATP channels in the pancreas. We hypothesized that the risk of acute coronary syndrome (ACS) events would be higher in patients using glyburide compared with gliclazide. This nested case-control study used administrative health data from Alberta, Canada. New users of glyburide or gliclazide aged ≥66 years between 1998 and 2010 were included. Cases were individuals with an ACS-related hospitalization or death. Up to four controls were matched based on birth year, sex, cohort-entry year and follow-up time. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (OR), controlling for baseline drug use and co-morbidities. Our cohort included 7441 gliclazide and 13 884 glyburide users; 51.4% men, mean (s.d.) age 75.5 (6.6) years and mean (s.d.) duration of follow-up 5.5 (4.0) years. A total of 4239 patients had an ACS-related hospitalization or death and were matched to 16 723 controls. Compared with gliclazide use, glyburide use was associated with a higher risk (adjusted OR 1.14; 95% CI 1.06-1.23) of ACS-related hospitalization or death over 5.5 years (number needed to harm: 50). In this observational study, glyburide use was associated with a 14% higher risk of ACS events compared with gliclazide use. Although the difference is small and probably to have implications at the population level rather than the individual patient or clinician, any causal inferences regarding sulfonylurea use and adverse cardiovascular risk should be tested in a large-scale randomized controlled trial. © 2013 John Wiley & Sons Ltd.

Surgery for subacromial impingement syndrome in relation to occupational exposures, lifestyle factors and diabetes mellitus: a nationwide nested case-control study.

PubMed

Dalbøge, Annett; Frost, Poul; Andersen, Johan Hviid; Svendsen, Susanne Wulff

2017-10-01

To estimate the risk of surgery for subacromial impingement syndrome (SIS) in relation to occupational exposures, lifestyle factors and diabetes mellitus. We conducted a case-control study nested in a register-based cohort study of the Danish working population. For each of 3000 first-time cases of surgery for SIS, two age-matched and sex-matched controls were drawn. Cases and controls received a questionnaire on job history and other factors. Job histories were combined with a psychosocial job exposure matrix (JEM) and the updated Shoulder JEM, which provided exposure intensities on measurement scales. Ten-year cumulative exposures to upper arm elevation >90°, repetitive shoulder movements, forceful shoulder exertions and hand-arm vibrations (HAVs) were estimated. We used conditional logistic regression. There were 5396 persons (60%) who answered the questionnaire. For occupational mechanical exposures, the adjusted OR (OR adj ) ranged from 1.9 (95% CI 1.5 to 2.5 for HAVs) to 2.5 (95% CI 1.9 to 3.5 for force) among men and 1.7 (95% CI 1.2 to 2.5 for HAVs) to 2.0 (95% CI 1.3 to 2.9 for force) among women. No statistically significant associations were found for occupational psychosocial factors. Body mass index (BMI) and pack-years of smoking showed OR adj up to 2.0. Diabetes mellitus showed OR adj of 1.5 (95% CI 1.1 to 2.2) for men and 2.2 (95% CI 1.4 to 3.4) for women. Our findings add to the evidence of an increased risk of surgery for SIS in relation to occupational cumulative mechanical exposures, even when an increased risk in relation to BMI, smoking and diabetes mellitus is taken into account. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Development of diagnostic prediction tools for bacteraemia caused by third-generation cephalosporin-resistant enterobacteria in suspected bacterial infections: a nested case-control study.

PubMed

Rottier, W C; van Werkhoven, C H; Bamberg, Y R P; Dorigo-Zetsma, J W; van de Garde, E M; van Hees, B C; Kluytmans, J A J W; Kuck, E M; van der Linden, P D; Prins, J M; Thijsen, S F T; Verbon, A; Vlaminckx, B J M; Ammerlaan, H S M; Bonten, M J M

2018-03-23

Current guidelines for the empirical antibiotic treatment predict the presence of third-generation cephalosporin-resistant enterobacterial bacteraemia (3GCR-E-Bac) in case of infection only poorly, thereby increasing unnecessary carbapenem use. We aimed to develop diagnostic scoring systems which can better predict the presence of 3GCR-E-Bac. A retrospective nested case-control study was performed that included patients ≥18 years of age from eight Dutch hospitals in whom blood cultures were obtained and intravenous antibiotics were initiated. Each patient with 3GCR-E-Bac was matched to four control infection episodes within the same hospital, based on blood-culture date and onset location (community or hospital). Starting from 32 commonly described clinical risk factors at infection onset, selection strategies were used to derive scoring systems for the probability of community- and hospital-onset 3GCR-E-Bac. 3GCR-E-Bac occurred in 90 of 22 506 (0.4%) community-onset infections and in 82 of 8110 (1.0%) hospital-onset infections, and these cases were matched to 360 community-onset and 328 hospital-onset control episodes. The derived community-onset and hospital-onset scoring systems consisted of six and nine predictors, respectively. With selected score cut-offs, the models identified 3GCR-E-Bac with sensitivity equal to existing guidelines (community-onset: 54.3%; hospital-onset: 81.5%). However, they reduced the proportion of patients classified as at risk for 3GCR-E-Bac (i.e. eligible for empirical carbapenem therapy) with 40% (95%CI 21-56%) and 49% (95%CI 39-58%) in, respectively, community-onset and hospital-onset infections. These prediction scores for 3GCR-E-Bac, specifically geared towards the initiation of empirical antibiotic treatment, may improve the balance between inappropriate antibiotics and carbapenem overuse. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

rhBMP-2 protects against reoperation for pseudoarthrosis and/or instrumentation failure: A matched case-control study of 448 patients.

PubMed

Macki, Mohamed; Syeda, Sbaa; Kerezoudis, Panagiotis; Bydon, Ali; Witham, Timothy F; Sciubba, Daniel M; Wolinsky, Jean-Paul; Bydon, Mohamad; Gokaslan, Ziya

2016-10-01

The objective of this independent study is to determine the impact of recombinant human bone morphogenetic protein 2 (rhBMP-2) on reoperation for pseudarthrosis and/or instrumentation failure. A nested case-control study of first-time posterolateral, instrumented fusion of the lumbar spine for degenerative spinal disease was undertaken. Cases of reoperation for pseudoarthrosis and/or instrumentation failure were assigned to controls, who did not experience the primary outcome measure at the time of reoperation. Cases and controls were matched on number of interspaces fused and inclusion of interbody. Predictors of reoperation for pseudoarthrosis and/or instrumentation failure were assessed with a conditional logistical regression controlling for rhBMP-2, age, obesity, and smoking. Of the 448 patients, 155 cases of reoperation for pseudoarthrosis and/or instrumentation were matched with 293 controls. Twenty-six percent of first-time surgeries included rhBMP-2, which was statistically more commonly used in the control cohort (33.11%) versus the case cohort (12.90%) (Unadjusted odds ratio [ORunadj]=0.28) (95% confidence interval [CI]: 0.16-0.49). Following a multivariate analysis controlling for age, obesity, and smoking, the rhBMP-2 recipients incurred a 73% lower odds of reoperation for pseudoarthrosis and/or instrumentation failure (95% CI, 0.15-0.48). Neither sarcomatous nor osseous neoplasm was detected in the study population. Mean follow up did not differ between the cases (81.57±standard deviation [SD] 4.98months) versus controls (74.75±2.49month) (ORunadj=1.01) (95% CI: 1.00-1.01). rhBMP-2 in lumbar fusion constructs protects against reoperation for pseudoarthrosis and/or instrumentation failure. However, the decision to include fusion supplements should be weighted between surgical determinants and clinical outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Risk factors for Kaposi's sarcoma in human immunodeficiency virus patients after initiation of antiretroviral therapy: A nested case-control study in Kenya.

PubMed

Lupia, Rodgers; Wabuyia, Peter B; Otiato, Peter; Fang, Chi-Tai; Tsai, Feng-Jen

2017-12-01

This study aimed to evaluate the association between highly active antiretroviral therapy (HAART) adherence and development of Kaposi's sarcoma (KS) in human immunodeficiency virus (HIV)/AIDS patients. We conducted a retrospective nested case-control study of 165 participants (33 cases and 132 controls) receiving HAART care at Maseno Hospital, Kenya, from January 2005 to October 2013. Cases were HIV-positive adults with KS, who were matched with controls in a ratio of 1:4 based on age (±5 years of each case), sex, and KS diagnosis date. Perfect adherence to HAART was assessed on every clinic visit by patients' self-reporting and pill counts. Chi-square tests were performed to compare socioeconomic and clinical statuses between cases and controls. A conditional logistic regression was used to assess the effects of perfect adherence to HAART, the latest CD4 count, education level, distance to health-care facility, initial World Health Organization stage, and number of regular sexual partners on the development of KS. Only 63.6% participants reported perfect adherence, and the control group had a significantly higher percentage of perfect adherence (75.0%) than did cases (18.2%). After adjustment for potential imbalances in the baseline and clinical characteristics, patients with imperfect HAART adherence had 20-times greater risk of developing KS than patients with perfect HAART adherence [hazard ratios: 21.0, 95% confidence interval: 4.2-105.1]. Patients with low latest CD4 count (≤350 cells/mm 3 ) had a seven-times greater risk of developing KS than did their counterparts (HRs: 7.1, 95% CI: 1.4-36.2). Imperfect HAART adherence and low latest CD4 count are significantly associated with KS development. Copyright © 2015. Published by Elsevier B.V.

Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study.

PubMed

Antoniou, Tony; Gomes, Tara; Mamdani, Muhammad M; Yao, Zhan; Hellings, Chelsea; Garg, Amit X; Weir, Matthew A; Juurlink, David N

2011-09-12

To characterise the risk of admission to hospital for hyperkalaemia in elderly patients treated with trimethoprim-sulfamethoxazole in combination with spironolactone. Population based nested case-control study. Ontario, Canada, from 1 April 1992 to 1 March 2010. Cases were residents of Ontario aged 66 years or above receiving chronic treatment with spironolactone and admitted to hospital with hyperkalaemia within 14 days of receiving a prescription for either trimethoprim-sulfamethoxazole, amoxicillin, norfloxacin, or nitrofurantoin. Up to four controls for each case were identified from the same cohort, matched on age, sex, and presence or absence of chronic kidney disease and diabetes, and required to have received one of the study antibiotics within 14 days before the case's index date. Odds ratio for association between admission to hospital with hyperkalaemia and receipt of a study antibiotic in the preceding 14 days, adjusted for conditions and drugs that may influence risk of hyperkalaemia. During the 18 year study period, 6903 admissions for hyperkalaemia were identified, 306 of which occurred within 14 days of antibiotic use. Of these, 248 (81%) cases were matched to 783 controls. 10.8% (17,859/165,754) of spironolactone users received at least one prescription for trimethoprim-sulfamethoxazole. Compared with amoxicillin, prescription of trimethoprim-sulfamethoxazole was associated with a marked increase in the risk of admission to hospital for hyperkalaemia (adjusted odds ratio 12.4, 95% confidence interval 7.1 to 21.6). The population attributable fraction was 59.7%, suggesting that approximately 60% of all cases of hyperkalaemia in older patients taking spironolactone and treated with an antibiotic for a urinary tract infection could be avoided if trimethoprim-sulfamethoxazole was not prescribed. Treatment with nitrofurantoin was also associated with an increase in the risk of hyperkalaemia (adjusted odds ratio 2.4, 1.3 to 4.6), but no such risk was found with norfloxacin (adjusted odds ratio 1.6, 0.8 to 3.4) Among older patients receiving spironolactone, treatment with trimethoprim-sulfamethoxazole was associated with a major increase in the risk of admission to hospital for hyperkalaemia. This drug combination should be avoided when possible.

Baseline Serum Estradiol and Fracture Reduction During Treatment With Hormone Therapy: The Women’s Health Initiative Randomized Trial

PubMed Central

Cauley, Jane A.; LaCroix, Andrea Z.; Robbins, John A.; Larson, Joseph; Wallace, Robert; Wactawski-Wende, Jean; Chen, Zhao; Bauer, Douglas C.; Cummings, Steven R.; Jackson, Rebecca

2009-01-01

Purpose To test the hypothesis that the reduction in fractures with hormone therapy (HT) is greater in women with lower estradiol levels. Methods We conducted a nested case-control study within the Women’s Health Initiative HT Trials. The sample included 231 hip fracture case-control pairs and a random sample of 519 all fracture case-control pairs. Cases and controls were matched for age, ethnicity, randomization date, fracture history and hysterectomy status. Hormones were measured prior to randomization. Incident cases of fracture identified over an average follow-up of 6.53 years. Results There was no evidence that the effect of HT on fracture differed by baseline estradiol (E2) or sex hormone binding globulin (SHBG). Across all quartiles of E2 and SHBG, women randomized to HT had about a 50% lower risk of fracture including hip fracture, compared to placebo. Conclusion The effect of HT on fracture reduction is independent of estradiol and SHBG levels. PMID:19436934

Worker substance use, workplace problems and the risk of occupational injury: a matched case-control study.

PubMed

Spicer, Rebecca S; Miller, Ted R; Smith, Gordon S

2003-07-01

This study examines the tendency toward problem behavior as an explanation for the relationship between problem substance use and occupational injury. The authors used a matched case-control study nested in a cohort of 26,413 workers, in which cases (n = 3,994) were workers suffering an occupational injury. Five controls per case (n = 19,970) were selected from the cohort of workers active on the day of the injury and matched on job type. Conditional logistic regression modeled the association of problem substance use with occupational injury, controlling for problem behaviors and worker characteristics. Problem substance use was indicated indirectly if any of the following were alcohol/drug-involved during the comparison period: Employee Assistance Program visit, excused absence or disciplinary action. Discipline records identified minor (absenteeism) and serious (dishonesty, theft, assault, harassment, disrespect) problem behaviors during the comparison period. The odds of injury among workers with an indicator of problem substance use was 1.35 (p = .015) times greater than the odds among workers without an indicator, controlling for job type and demographics as well as adjusting for exposure. This ratio declined to 1.21 (p = .138) when problem behaviors were also controlled for. Minor and serious problem behaviors were significantly associated with occupational injury (odds ratio [OR] = 1.73, p < .001, and OR = 2.19, p < .001, respectively), controlling for demographics and substance use. The relationship of problem substance use with occupational injury was weak when problem behaviors were controlled for, suggesting that this relationship, observed in previous studies, may be explained by a workers tendency toward problem behaviors. Workplace injury prevention programs should address the expression of problem behaviors as a complement to drug and alcohol deterrent programs.

Bumblebee calligraphy: the design and control of flight motifs in the learning and return flights of Bombus terrestris.

PubMed

Philippides, Andrew; de Ibarra, Natalie Hempel; Riabinina, Olena; Collett, Thomas S

2013-03-15

Many wasps and bees learn the position of their nest relative to nearby visual features during elaborate 'learning' flights that they perform on leaving the nest. Return flights to the nest are thought to be patterned so that insects can reach their nest by matching their current view to views of their surroundings stored during learning flights. To understand how ground-nesting bumblebees might implement such a matching process, we have video-recorded the bees' learning and return flights and analysed the similarities and differences between the principal motifs of their flights. Loops that take bees away from and bring them back towards the nest are common during learning flights and less so in return flights. Zigzags are more prominent on return flights. Both motifs tend to be nest based. Bees often both fly towards and face the nest in the middle of loops and at the turns of zigzags. Before and after flight direction and body orientation are aligned, the two diverge from each other so that the nest is held within the bees' fronto-lateral visual field while flight direction relative to the nest can fluctuate more widely. These and other parallels between loops and zigzags suggest that they are stable variations of an underlying pattern, which enable bees to store and reacquire similar nest-focused views during learning and return flights.

A nested case-control study of leukemia mortality and ionizing radiation at the Portsmouth Naval Shipyard.

PubMed

Kubale, Travis L; Daniels, Robert D; Yiin, James H; Couch, James; Schubauer-Berigan, Mary K; Kinnes, Gregory M; Silver, Sharon R; Nowlin, Susan J; Chen, Pi-Hsueh

2005-12-01

A nested case-control study using conditional logistic regression was conducted to evaluate the exposure-response relationship between external ionizing radiation exposure and leukemia mortality among civilian workers at the Portsmouth Naval Shipyard (PNS), Kittery, Maine. The PNS civilian workers received occupational radiation exposure while performing construction, overhaul, repair and refueling activities on nuclear-powered submarines. The study age-matched 115 leukemia deaths with 460 controls selected from a cohort of 37,853 civilian workers employed at PNS between 1952 and 1992. In addition to radiation doses received in the workplace, a secondary analysis incorporating doses from work-related medical X rays and other occupational radiation exposures was conducted. A significant positive association was found between leukemia mortality and external radiation exposure, adjusting for gender, radiation worker status, and solvent exposure duration (OR = 1.08 at 10 mSv of exposure; 95% CI = 1.01, 1.16). Solvent exposure (including benzene and carbon tetrachloride) was also significantly associated with leukemia mortality adjusting for radiation dose, radiation worker status, and gender. Incorporating doses from work-related medical X rays did not change the estimated leukemia risk per unit of dose.

Incidence of and risk factors for severe hypoglycaemia in treated type 2 diabetes mellitus patients in the UK--a nested case-control analysis.

PubMed

Bruderer, S G; Bodmer, M; Jick, S S; Bader, G; Schlienger, R G; Meier, C R

2014-09-01

To assess incidence rates (IRs) of and identify risk factors for incident severe hypoglycaemia in patients with type 2 diabetes newly treated with antidiabetic drugs. Using the UK-based General Practice Research Database, we performed a retrospective cohort study between 1994 and 2011 and a nested case-control analysis. Ten controls from the population at risk were matched to each case with a recorded severe hypoglycaemia during follow-up on general practice, years of history in the database and calendar time. Using multivariate conditional logistic regression analyses, we adjusted for potential confounders. Of 130,761 patients with newly treated type 2 diabetes (mean age 61.7 ± 13.0 years), 690 (0.5%) had an incident episode of severe hypoglycaemia recorded [estimated IR 11.97 (95% confidence interval, CI, 11.11-12.90) per 10,000 person-years (PYs)]. The IR was markedly higher in insulin users [49.64 (95% CI, 44.08-55.89) per 10,000 PYs] than in patients not using insulin [8.03 (95% CI, 7.30-8.84) per 10,000 PYs]. Based on results of the nested case-control analysis increasing age [≥ 75 vs. 20-59 years; adjusted odds ratio (OR), 2.27; 95% CI, 1.65-3.12], cognitive impairment/dementia (adjusted OR, 2.00; 95% CI, 1.37-2.91), renal failure (adjusted OR, 1.34; 95% CI, 1.04-1.71), current use of sulphonylureas (adjusted OR, 4.45; 95% CI, 3.53-5.60) and current insulin use (adjusted OR, 11.83; 95% CI, 9.00-15.54) were all associated with an increased risk of severe hypoglycaemia. Severe hypoglycaemia was recorded in 12 cases per 10,000 PYs. Risk factors for severe hypoglycaemia included increasing age, renal failure, cognitive impairment/dementia, and current use of insulin or sulphonylureas. © 2014 John Wiley & Sons Ltd.

Biomarkers and bacterial pneumonia risk in patients with treated HIV infection: a case-control study.

PubMed

Bjerk, Sonja M; Baker, Jason V; Emery, Sean; Neuhaus, Jacqueline; Angus, Brian; Gordin, Fred M; Pett, Sarah L; Stephan, Christoph; Kunisaki, Ken M

2013-01-01

Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIV-infected patients do not currently exist. We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1∶1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer were compared between cases and controls. Cases (n = 72) and controls (n = 72) were 25.7% female, 51.4% black, 65.3% current smokers, 9.7% diabetic, 36.1% co-infected with Hepatitis B/C, and 75.0% were on cART at baseline. Median (IQR) age was 45 (41, 51) years with CD4+ count of 553 (436, 690) cells/mm(3). Baseline CC16 and SP-D were similar between cases and controls, but hsCRP was significantly higher in cases than controls (2.94 µg/mL in cases vs. 1.93 µg/mL in controls; p = 0.02). IL-6 and d-dimer levels were also higher in cases compared to controls, though differences were not statistically significant (p-value 0.06 and 0.10, respectively). In patients with cART-treated HIV infection, higher levels of systemic inflammatory markers were associated with increased bacterial pneumonia risk, while two pulmonary-specific inflammatory biomarkers, CC16 and SP-D, were not associated with bacterial pneumonia risk.

Predictors of early postpartum mental distress in mothers with midwifery home care--results from a nested case-control study.

PubMed

Staehelin, Katharina; Kurth, Elisabeth; Schindler, Christian; Schmid, Monika; Zemp Stutz, Elisabeth

2013-08-27

The prevalence of early postpartum mental health conditions is high. Midwives and other health professionals visiting women at home may identify mothers at risk. This seems crucial given decreasing trends of length of hospital stay after childbirth. This study aimed to identify predictors of maternal mental distress in a midwifery home care setting. Using the statistical database of independent midwives' services in Switzerland in 2007, we conducted a matched nested case-control study. Out of a source population of 34,295 mothers with midwifery home care in the first ten days after childbirth, 935 mothers with maternal distress and 3,645 controls, matched by midwife, were included. We analysed whether socio-demographic, maternal and neonatal factors predict maternal mental distress by multivariable conditional logistic regression analysis. Infant crying problems and not living with a partner were the strongest predictors for maternal distress, whereas higher parity was the most protective factor. Significantly elevated risks were also found for older age, lower educational levels, breast/breastfeeding problems, infant weight gain concerns, neonatal pathologies and use of midwifery care during pregnancy. A lower likelihood for maternal distress was seen for non-Swiss nationality, full-time employment before birth, intention to return to work after birth and midwife-led birth. The study informs on predictors of maternal mental distress identified in a home care setting in the early postpartum period. Midwives and other health care professionals should pay particular attention to mothers of excessively crying infants, single mothers and primipara, and assess the need for support of these mothers.

A nested case-control study of fatal work related injuries among Brazilian steel workers.

PubMed Central

Barreto, S M; Swerdlow, A J; Smith, P G; Higgins, C D

1997-01-01

OBJECTIVES: To estimate the relative risk of death from work related injury in a steelworks, associated with exposure to various occupational hazards, sociodemographic factors, and medical history. MATERIAL AND METHODS: The study was a nested case-control design. It was based on a cohort of men employed in the steel plant of USIMINAS, Brazil between January 1977 and August 1990, who were followed up to November 1992. The cases were defined as all workers in the cohort who died from injury in the study period and whose death had been notified to the Brazilian Ministry of Labour as being related to work. Four controls per case, matched to cases on year of birth, were randomly selected from among workers employed in the plant at the time of death of the matching case. Data on potential risk factors for occupational injury were extracted from company records; for the controls these data were abstracted for the period preceding the death of the matching case. RESULTS: There were 37 deaths related to work injuries during the study period. Four surviving workers were selected as controls for each case, but for eight the personnel records were incomplete, leaving 140 controls in all. Significantly increased risk of fatal injury related to work was associated with exposure to noise, heat, dust and fumes, gases and vapours, rotating shift work, being a manual worker, and working in the steel mill, coke ovens, blast furnaces, and energy and water supply areas. Risk of fatal injury related to work increased with intensity of exposure to noise (P (trend) = 0.004) and heat (P < 0.001), and increased greatly with a hazard score that combined information on noise, heat, dust, and gas exposure (P < 0.001). Number of years of schooling (P = 0.03) and salary level (P = 0.03) were both negatively associated with risk. In a multivariate analysis including all these significant factors, only hazard score and area of work remained associated with death from injury related to work. The highest risks were for men exposed to all four environmental hazards (odds ratio (OR) 19.4; 95% confidence interval (95% CI) 1.1 to 352.1) and those working in the energy supply area (OR 18.0; 1.6 to 198.1). CONCLUSIONS: The study identified parts of the steelworks and types of hazard associated with greatly increased risk of fatal accident. Research and measures to prevent accidents need to concentrate on these areas and the people working in them. The use of a hazard score was successful in identifying high risk, and similar scoring might prove useful in other industrial situations. PMID:9326164

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

PubMed

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

2013-08-01

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

Effect of statin on hepatocellular carcinoma in patients with type 2 diabetes: A nationwide nested case-control study.

PubMed

Kim, Gyuri; Jang, Suk-Yong; Han, Eugene; Lee, Yong-Ho; Park, Se-Young; Nam, Chung Mo; Kang, Eun Seok

2017-02-15

Relationship on new statin use and the risk of hepatocellular carcinoma (HCC) in patients with incident type 2 diabetes mellitus (T2DM), who might be at the risk of developing HCC, is uncertained. A nationwide population-based nested case-control study was conducted within the National Health Insurance Service National Sample Cohort 2002-2013 in Korea. Newly prescribed statin after newly diagnosed T2DM was defined as statin use. Controls were matched to case patients on age, sex, follow-up time, and the date of diabetes diagnosis at a five-to-one ratio. Odds ratios (ORs) for associations of statin use with HCC were calculated using conditional logistic regression. After at least a 5-year HCC-free period, there were 229 incident HCC cases and 1,145 matched controls from 47,738 patients with incident diabetes. Of these 229 incident HCC cases, 27 (11.8%) were statin users, whereas 378 (33.0%) were statin users among 1,145 controls. Statin use was associated with a reduced risk of HCC development (adjusted OR [AOR]= 0.36, 95% confidence interval [CI] 0.22-0.60) after adjustment for chronic viral hepatitis, liver cirrhosis, alcoholic liver disease, previous cancer, aspirin use, insulin use, sulfonylurea use, metformin use, thiazolidinedione use, history of chronic obstructive pulmonary disease, Charlson comorbidity score, household income level, and residential area. Risk reduction was accentuated with an increase of cumulative defined daily doses (cDDD) compared with non-users (AORs 0.53, 0.36, 0.32, and 0.26 in ≤60, 60-180, 181-365, and >365cDDD, respectively; P for trend <0.0001). The risk reduction was apparent in the presence of liver disease (AOR = 0.27, 95% CI 0.14-0.50), including heterogeneous groups of clinical diagnosis of liver disease, but not significant in the absence of liver disease (AOR = 0.64, 95% CI 0.32-1.29). Among patients with new onset T2DM, statin use before HCC diagnosis may have a beneficial inhibitory effect on HCC development in a dose-dependent manner, especially in individuals with liver disease. © 2016 UICC.

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.

Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study

PubMed Central

Gomes, Tara; Mamdani, Muhammad M; Yao, Zhan; Hellings, Chelsea; Garg, Amit X; Weir, Matthew A; Juurlink, David N

2011-01-01

Objectives To characterise the risk of admission to hospital for hyperkalaemia in elderly patients treated with trimethoprim-sulfamethoxazole in combination with spironolactone. Design Population based nested case-control study. Setting Ontario, Canada, from 1 April 1992 to 1 March 2010. Participants Cases were residents of Ontario aged 66 years or above receiving chronic treatment with spironolactone and admitted to hospital with hyperkalaemia within 14 days of receiving a prescription for either trimethoprim-sulfamethoxazole, amoxicillin, norfloxacin, or nitrofurantoin. Up to four controls for each case were identified from the same cohort, matched on age, sex, and presence or absence of chronic kidney disease and diabetes, and required to have received one of the study antibiotics within 14 days before the case’s index date. Main outcome measures Odds ratio for association between admission to hospital with hyperkalaemia and receipt of a study antibiotic in the preceding 14 days, adjusted for conditions and drugs that may influence risk of hyperkalaemia. Results During the 18 year study period, 6903 admissions for hyperkalaemia were identified, 306 of which occurred within 14 days of antibiotic use. Of these, 248 (81%) cases were matched to 783 controls. 10.8% (17 859/165 754) of spironolactone users received at least one prescription for trimethoprim-sulfamethoxazole. Compared with amoxicillin, prescription of trimethoprim-sulfamethoxazole was associated with a marked increase in the risk of admission to hospital for hyperkalaemia (adjusted odds ratio 12.4, 95% confidence interval 7.1 to 21.6). The population attributable fraction was 59.7%, suggesting that approximately 60% of all cases of hyperkalaemia in older patients taking spironolactone and treated with an antibiotic for a urinary tract infection could be avoided if trimethoprim-sulfamethoxazole was not prescribed. Treatment with nitrofurantoin was also associated with an increase in the risk of hyperkalaemia (adjusted odds ratio 2.4, 1.3 to 4.6), but no such risk was found with norfloxacin (adjusted odds ratio 1.6, 0.8 to 3.4) Conclusions Among older patients receiving spironolactone, treatment with trimethoprim-sulfamethoxazole was associated with a major increase in the risk of admission to hospital for hyperkalaemia. This drug combination should be avoided when possible. PMID:21911446

Ischaemic cardiac events and use of strontium ranelate in postmenopausal osteoporosis: a nested case-control study in the CPRD.

PubMed

Cooper, C; Fox, K M; Borer, J S

2014-02-01

We explored the cardiac safety of the osteoporosis treatment strontium ranelate in the UK Clinical Practice Research Datalink. While known cardiovascular risk factors like obesity and smoking were associated with increased cardiac risk, use of strontium ranelate was not associated with any increase in myocardial infarction or cardiovascular death. It has been suggested that strontium ranelate may increase risk for cardiac events in postmenopausal osteoporosis. We set out to explore the cardiac safety of strontium ranelate in the Clinical Practice Research Datalink (CPRD) and linked datasets. We performed a nested case-control study. Primary outcomes were first definite myocardial infarction, hospitalisation with myocardial infarction, and cardiovascular death. Cases and matched controls were nested in a cohort of women treated for osteoporosis. The association with exposure to strontium ranelate was analysed by multivariate conditional logistic regression. Of the 112,445 women with treated postmenopausal osteoporosis, 6,487 received strontium ranelate. Annual incidence rates for first definite myocardial infarction (1,352 cases), myocardial infarction with hospitalisation (1,465 cases), and cardiovascular death (3,619 cases) were 3.24, 6.13, and 14.66 per 1,000 patient-years, respectively. Obesity, smoking, and cardiovascular treatments were associated with significant increases in risk for cardiac events. Current or past use of strontium ranelate was not associated with increased risk for first definite myocardial infarction (odds ratio [OR] 1.05, 95 % confidence interval [CI] 0.68-1.61 and OR 1.12, 95 % CI 0.79-1.58, respectively), hospitalisation with myocardial infarction (OR 0.84, 95 % CI 0.54-1.30 and OR 1.17, 95 % CI 0.83-1.66), or cardiovascular death (OR 0.96, 95 % CI 0.76-1.21 and OR 1.16, 95 % CI 0.94-1.43) versus patients who had never used strontium ranelate. Analysis in the CPRD did not find evidence for a higher risk for cardiac events associated with the use of strontium ranelate in postmenopausal osteoporosis.

Association between sleep disorder and panic disorder in South Korea: Nationwide nested case-control study of data from 2004 to 2013.

PubMed

Park, Han Jin; Kim, Min Seok; Park, Eun-Cheol; Jang, Suk-Yong; Kim, Woorim; Han, Kyu-Tae

2017-12-05

After 2010, panic disorders became relatively common in South Korea, with many celebrities confessing to the public that they have panic disorder. The annual number of patients with panic disorder and sleep disorder have been gradually increasing. In light of these increases, we analyzed the relationship between sleep disorder and panic disorder. We used national claim data to design a 1:3 nested case-control study. The study included medical claims filed for 29,312 patients during 2004-2013. We performed conditional logistic regression analysis to investigate the relationship between sleep disorder and panic disorder. There were 7436 patients who were diagnosed with panic disorder, and 21,876 patients who were gender- and age-matched as controls. Patients with sleep disorder had higher incidence of panic disorder. In particular, patients with insomnia had the strongest association with panic disorder (adjusted, OR, 1.386; 95% CI, 1.201-1.599; p < 0.05). These associations were stronger in healthy patients and those with worse socioeconomic status. In conclusion, sleep disorder, in particular, insomnia was positively associated with panic disorder. Thus, healthcare professionals and policy makers should effectively control insomnia and consider strategies for early intervention for vulnerable patients with risk of panic disorder. Copyright © 2017. Published by Elsevier B.V.

Lung Cancer Risk from Occupational and Environmental Radon and Role of Smoking in Two Czech Nested Case-Control Studies

PubMed Central

Tomasek, Ladislav

2013-01-01

The aim of the present study was to evaluate the risk of lung cancer from combined exposure to radon and smoking. Methodologically, it is based on case-control studies nested within two Czech cohort studies of nearly 11,000 miners followed-up for mortality in 1952–2010 and nearly 12,000 inhabitants exposed to high levels of radon in homes, with mortality follow-up in 1960–2010. In addition to recorded radon exposure, these studies use information on smoking collected from the subjects or their relatives. A total of 1,029 and 370 cases with smoking information have been observed in the occupational and environmental (residential) studies, respectively. Three or four control subjects have been individually matched to cases according to sex, year of birth, and age. The combined effect from radon and smoking is analyzed in terms of geometric mixture models of which the additive and multiplicative models are special cases. The resulting models are relatively close to the additive interaction (mixing parameter 0.2 and 0.3 in the occupational and residential studies, respectively). The impact of the resulting model in the residential radon study is illustrated by estimates of lifetime risk in hypothetical populations of smokers and non-smokers. In comparison to the multiplicative risk model, the lifetime risk from the best geometric mixture model is considerably higher, particularly in the non-smoking population. PMID:23470882

Risk of Injurious Fall and Hip Fracture up to 26 y before the Diagnosis of Parkinson Disease: Nested Case-Control Studies in a Nationwide Cohort.

PubMed

Nyström, Helena; Nordström, Anna; Nordström, Peter

2016-02-01

Low muscle strength has been found in late adolescence in individuals diagnosed with Parkinson disease (PD) 30 y later. This study investigated whether this lower muscle strength also may translate into increased risks of falling and fracture before the diagnosis of PD. Among all Swedish citizens aged ≥50 y in 2005, two nested case-control cohorts were compiled. In cohort I, individuals diagnosed with PD during 1988-2012 (n = 24,412) were matched with up to ten controls (n = 243,363), and the risk of fall-related injuries before diagnosis of PD was evaluated. In cohort II, individuals with an injurious fall in need of emergency care during 1988-2012 (n = 622,333) were matched with one control (n = 622,333), and the risk of PD after the injurious fall was evaluated. In cohort I, 18.0% of cases and 11.5% of controls had at least one injurious fall (p < 0.001) prior to PD diagnosis in the case. Assessed by conditional logistic regression analysis adjusted for comorbid diagnoses and education level, PD was associated with increased risks of injurious fall up to 10 y before diagnosis (odds ratio [OR] 1.19, 95% CI 1.08-1.31; 7 to <10 y before diagnosis) and hip fracture ≥15 y before diagnosis (OR 1.36, 95% CI 1.10-1.69; 15-26 y before diagnosis). In cohort II, 0.7% of individuals with an injurious fall and 0.5% of controls were diagnosed with PD during follow-up (p < 0.001). The risk of PD was increased for up to 10 y after an injurious fall (OR 1.18, 95% CI 1.02-1.37; 7 to <10 y after diagnosis). An important limitation is that the diagnoses were obtained from registers and could not be clinically confirmed for the study. The increased risks of falling and hip fracture prior to the diagnosis of PD may suggest the presence of clinically relevant neurodegenerative impairment many years before the diagnosis of this disease.

Risk factors for long-bone fractures in children up to 5 years of age: a nested case-control study.

PubMed

Baker, Ruth; Orton, Elizabeth; Tata, Laila J; Kendrick, Denise

2015-05-01

To investigate risk factors for first long-bone fractures in children up to 5 years old in order to provide evidence about which families could benefit from injury prevention interventions. Population-based matched nested case-control study using The Health Improvement Network, a UK primary care research database, 1988-2004. Maternal, household and child risk factors for injury were assessed among 2456 children with long-bone fractures (cases). 23,661 controls were matched to cases on general practice. Adjusted ORs and 95% CIs were estimated using conditional logistic regression. Fractures of long-bones were independently associated with younger maternal age and higher birth order, with children who were the fourth-born in the family, or later, having a threefold greater odds of fracture compared to first-born children (adjusted OR 3.12, 95% CI 2.08 to 4.68). Children over the age of 1 year had a fourfold (13-24 months, adjusted OR 4.09 95% CI 3.51 to 4.76) to fivefold (37+ months, adjusted OR 4.88 95% CI 4.21 to 5.66) increase in the odds of a long-bone fracture compared to children aged 0-12 months. Children in families with a history of maternal alcohol misuse had a raised odds of long-bone fracture (adjusted OR 2.33, 95% CI 1.13 to 4.82) compared to those with no documented history. Risk factors for long-bone fractures in children less than 5 years old included age above 1 year, increasing birth order, younger maternal age and maternal alcohol misuse. These risk factors should be used to prioritise families and communities for injury prevention interventions. 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.

Plasma Soluble CD30 as a Possible Marker of Adult T-cell Leukemia in HTLV-1 Carriers: a Nested Case-Control Study.

PubMed

Takemoto, Shigeki; Iwanaga, Masako; Sagara, Yasuko; Watanabe, Toshiki

2015-01-01

Elevated levels of soluble CD30 (sCD30) are linked with various T-cell neoplasms. However, the relationship between sCD30 levels and the development of adult T-cell leukemia (ATL) in human T-cell leukemia virus type 1 (HTLV-1) carriers remains to be clarified. We here investigated whether plasma sCD30 is associated with risk of ATL in a nested case-control study within a cohort of HTLV-1 carriers. We compared sCD30 levels between 11 cases (i.e., HTLV-1 carriers who later progressed to ATL) and 22 age-, sex- and institution-matched control HTLV-1 carriers (i.e., those with no progression). The sCD30 concentration at baseline was significantly higher in cases than in controls (median 65.8, range 27.2-134.5 U/mL vs. median 22.2, range 8.4-63.1 U/mL, P=0.001). In the univariate logistic regression analysis, a higher sCD30 (≥30.2 U/mL) was significantly associated with ATL development (odds ratio 7.88 and the 95% confidence intervals 1.35-45.8, P = 0.02). Among cases, sCD30 concentration tended to increase at the time of diagnosis of aggressive-type ATL, but the concentration was stable in those developing the smoldering-type. This suggests that sCD30 may serve as a predictive marker for the onset of aggressive-type ATL in HTLV-1 carriers.

Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study

PubMed Central

Gan, Ryan W.; Young, Kendra A.; Zerbe, Gary O.; Demoruelle, M. Kristen; Weisman, Michael H.; Buckner, Jane H.; Gregersen, Peter K.; Mikuls, Ted R.; O’Dell, James R.; Keating, Richard M.; Clare-Salzler, Michael J.; Deane, Kevin D.; Holers, V. Michael

2016-01-01

Objective. The aim of this study was to investigate omega-3 fatty acid (FA) supplement use and omega-3 FAs in erythrocyte membranes [omega-3 FA % in erythrocyte membranes (RBC)] and their association with anti-CCP autoantibodies in a population without RA, but who are at genetic risk for RA. Methods. The multicentre Studies of the Etiology of RA (SERA) cohort includes RA-free subjects who are first-degree relatives of RA probands or are enriched with the HLA-DR4 allele. In a nested case-control study, 30 SERA cases were identified who were anti-CCP2 antibody positive. We further identified 47 autoantibody negative controls, frequency matched to cases on age at study visit, sex, race and study site. Anti-CCP2 status, self-reported omega-3 FA supplement use and omega-3 FA % in RBCs were obtained from a single visit. Results. Anti-CCP2 positive cases were less likely than controls to report omega-3 FA supplement use (odds ratio: 0.14; 95% CI 0.03, 0.68). In addition, the likelihood of anti-CCP2 positivity was inversely associated with total omega-3 FA % in RBCs (odds ratio: 0.47; 95% CI 0.24, 0.92, for a s.d. increase). Conclusion. The inverse association between anti-CCP2 positivity and self-reported omega-3 FA supplement use and omega-3 FA % in RBCs suggests that omega-3 FAs may protect against the development of RA-related autoimmunity in pre-clinical RA. PMID:26370400

Employment history indicators and mortality in a nested case-control study from the Spanish WORKing life social security (WORKss) cohort

PubMed Central

2017-01-01

Employment has transitioned from stable to more flexible schemes. Little is known about the effects of dynamic working lives and mortality. We examined the association of employment, unemployment and inactivity on mortality among workers born in 1926–1988, in a nested case-control study of workers from the Spanish WORKss cohort. Cases were all deaths that occurred during 2004–2013 and controls were living persons, matched for sex and age at the time the case occurred. We had information on employment from 1981 to 2013. Logistic regression was used to measure the associations between the 3 employment history indicators separately by sex. There were 53,989 cases and an equal number of controls (n = 107,978). More than 16 years employed showed a protective effect against mortality in women (OR = 0.88, 95%CI: 0.81, 0.94) and men (OR = 0.76, 95%CI: 0.70, 0.79). The number of spells and time in unemployment and inactivity were significantly related to mortality in men, but not women. Sensitivity analyses by labor relationship showed stronger associations of unemployment (OR = 1.42, 95%CI: 1.13, 1.78) and inactivity (OR = 1.34; 95%CI: 1.09, 1.65) for temporary workers. Employment gaps are detrimental to health and have worse effects if the gaps occur without unemployment benefits or after temporary contracts. These results may drive improvement of labor and social policies that protect workers against the potential negative effects of dynamic work lives. PMID:28570614

Air Pollution and Pulmonary Tuberculosis: A Nested Case–Control Study among Members of a Northern California Health Plan

PubMed Central

Smith, Geneé S.; Van Den Eeden, Stephen K.; Garcia, Cynthia; Shan, Jun; Baxter, Roger; Herring, Amy H.; Richardson, David B.; Van Rie, Annelies; Emch, Michael; Gammon, Marilie D.

2016-01-01

Background: Ecologic analyses, case–case comparisons, and animal experiments suggest positive associations between air pollution and tuberculosis. Objectives: We evaluated this hypothesis in a large sample, which yielded results that are applicable to the general population. Methods: We conducted a case–control study nested within a cohort of Kaiser Permanente of Northern California members. All active pulmonary tuberculosis (TB) cases newly diagnosed between 1996 and 2010 (n = 2,309) were matched to two controls (n = 4,604) by age, sex, and race/ethnicity on the index date corresponding with the case diagnosis date. Average individual-level concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) and 10 μm (PM10) for 2 years before diagnosis/entry into the study were estimated using measurements from the California Air Resources Board monitor closest to the participant’s residence. Results: In single-pollutant adjusted conditional logistic regression models, the pulmonary TB odds ratios (95% confidence intervals) for the highest quintile (vs. lowest) were 1.50 (95% CI: 1.15, 1.95) for CO and 1.42 (95% CI: 1.10, 1.84) for NO2. Corresponding estimates were higher among never [1.68 (95% CI: 1.26, 2.24)] than ever [1.19 (95% CI: 0.74, 1.92)] smokers for CO. In contrast, for NO2, estimates were higher among ever [1.81 (95% CI: 1.13, 2.91)] than never [1.29 (95% CI: 0.97, 1.71)] smokers. O3 was inversely associated for smokers [0.66 (95% CI: 0.43, 1.02)] and never smokers [0.65 (95% CI: 0.52, 0.81)]. No other consistent patterns were observed. Conclusions: In this first, to our knowledge, U.S. nested case–control study on air pollution and pulmonary TB, we observed positive associations with ambient CO and NO2, which require confirmation. Citation: Smith GS, Van Den Eeden SK, Garcia C, Shan J, Baxter R, Herring AH, Richardson DB, Van Rie A, Emch M, Gammon MD. 2016. Air pollution and pulmonary tuberculosis: a nested case-control study among members of a Northern California health plan. Environ Health Perspect 124:761–768; http://dx.doi.org/10.1289/ehp.1408166 PMID:26859438

Real-world antidiabetic drug use and fracture risk in 12,277 patients with type 2 diabetes mellitus: a nested case-control study.

PubMed

Losada, E; Soldevila, B; Ali, M S; Martínez-Laguna, D; Nogués, X; Puig-Domingo, M; Díez-Pérez, A; Mauricio, D; Prieto-Alhambra, D

2018-06-02

We conducted a nested case-control study to study the association between antidiabetic treatments (alone or in combination) use and fracture risk among incident type 2 Diabetes mellitus patients. We found an increased risk of bone fracture with insulin therapy compared to metformin monotherapy. Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures, to which antidiabetic therapies may contribute. We aimed to characterize the risk of fracture associated with different antidiabetic treatments as usually prescribed to T2DM patients in actual practice conditions. A case-control study was nested within a cohort of incident T2DM patients registered in 2006-2012 in the Information System for Research Development in Primary Care (Catalan acronym, SIDIAP), a database which includes records for > 5.5 million patients in Catalonia (Spain). Each case (incident major osteoporotic fracture) was risk-set matched with up to five same-sex controls by calendar year of T2DM diagnosis and year of birth (± 10 years). Study exposure included previous use of all antidiabetic medications (alone or in combination), as dispensed in the 6 months before the index date, with metformin (MTF) monotherapy, the most commonly used drug, as a reference group (active comparator). Data on 12,277 T2DM patients (2049 cases and 10,228 controls) were analyzed. Insulin use was associated with increased fracture risk (adjusted OR 1.63 (95% CI 1.30-2.04)), as was the combination of MTF and sulfonylurea (SU) (adjusted OR 1.29 (1.07-1.56)), compared with MTF monotherapy. Sensitivity analyses suggest possible causality for insulin therapy but not for the MTF + SU combination association. No significant association was found with any other antidiabetic medications. Insulin monotherapy was associated with an increased fracture risk compared to MTF monotherapy in T2DM patients. Fracture risk should be taken into account when starting a glucose-lowering drug as part of T2DM treatment.

Cancer risk in relation to serum copper levels.

PubMed

Coates, R J; Weiss, N S; Daling, J R; Rettmer, R L; Warnick, G R

1989-08-01

A nested, matched case-control study was conducted to assess the relationship between serum levels of copper and the subsequent risk of cancer. One hundred thirty-three cases of cancer were identified during 1974-1984 among 5000 members of a northwest Washington State employee cohort from whom serum specimens had been previously obtained and stored. Two hundred forty-one controls were selected at random from the cohort and were matched to the cases on the basis of age, sex, race, and date of blood draw. Serum copper levels were measured by atomic absorption spectrometry. Risk of a subsequent diagnosis of cancer was positively associated with serum copper levels, but only among those cases diagnosed within 4 years of the time the serum specimens were collected. Among cases diagnosed more than 4 years after specimen collection, there was no consistent association between serum copper levels and risk. Adjustment for age, sex, race, occupational status, cigarette smoking, family history of cancer, alcohol consumption, and, among females, use of exogenous hormones had no appreciable effect on these relationships. The findings suggest that the presence of cancer may increase serum copper levels several years prior to its diagnosis. They are less supportive of the hypothesis that serum copper levels affect cancer risk.

Hospital-treated mental and behavioral disorders and risk of Alzheimer's disease: A nationwide nested case-control study.

PubMed

Tapiainen, V; Hartikainen, S; Taipale, H; Tiihonen, J; Tolppanen, A-M

2017-06-01

Studies investigating psychiatric disorders as Alzheimer's disease (AD) risk factors have yielded heterogeneous findings. Differences in time windows between the exposure and outcome could be one explanation. We examined whether (1) mental and behavioral disorders in general or (2) specific mental and behavioral disorder categories increase the risk of AD and (3) how the width of the time window between the exposure and outcome affects the results. A nationwide nested case-control study of all Finnish clinically verified AD cases, alive in 2005 and their age, sex and region of residence matched controls (n of case-control pairs 27,948). History of hospital-treated mental and behavioral disorders was available since 1972. Altogether 6.9% (n=1932) of the AD cases and 6.4% (n=1784) of controls had a history of any mental and behavioral disorder. Having any mental and behavioral disorder (adjusted OR=1.07, 95% CI=1.00-1.16) or depression/other mood disorder (adjusted OR=1.17, 95% CI=1.05-1.30) were associated with higher risk of AD with 5-year time window but not with 10-year time window (adjusted OR, 95% CI 0.99, 0.91-1.08 for any disorder and 1.08, 0.96-1.23 for depression). The associations between mental and behavioral disorders and AD were modest and dependent on the time window. Therefore, some of the disorders may represent misdiagnosed prodromal symptoms of AD, which underlines the importance of proper differential diagnostics among older persons. These findings also highlight the importance of appropriate time window in psychiatric and neuroepidemiology research. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Risk of severe acute liver injury among patients with brain cancer treated with temozolomide: a nested case-control study using the healthcore integrated research database.

PubMed

Desai, Vibha C A; Quinlan, Scott C; Deitz, Anne C; He, Jinghua; Holick, Crystal N; Lanes, Stephan

2017-08-01

Temozolomide (TMZ) is used to treat adult patients with glioblastoma multiforme (GBM). Cases of hepatotoxicity have been reported among patients using TMZ. The objective of the study was to assess the relation, if any, between exposure to TMZ and serious acute liver injury (SALI). We used the HealthCore Integrated Research Database to perform a case-control study nested within a retrospective cohort of adult patients aged 18-100 years with at least two diagnoses of brain cancer anytime between 2006 and 2014. Patients without continuous eligibility or with a SALI diagnosis within 6 months prior to the date of incident brain cancer diagnosis were excluded. Medical records were sought for potential SALI cases and reviewed by two hepatologists. Five controls were selected for each case using incidence density sampling, matched on age and calendar year of index date. The analysis included 61 confirmed SALI cases and 305 selected controls. Exposure to TMZ was classified according to dispensing date and days supply of medication dispensed. We estimated odds ratios using conditional logistic regression models. The odds ratio for any exposure to TMZ was 0.91 (95% CI 0.44-1.91), for recent exposure to TMZ was 0.62 (95% CI 0.21-1.85). There was no increased risk of SALI with increasing duration of exposure to TMZ. When patients with unconfirmed SALI were included in the analysis, results were similar (OR 1.04; 95% CI 0.70-1.54). In conclusion, this study did not find an association between TMZ and SALI risk among patients with brain cancer.

Association between Helicobacter pylori infection and increased risk of typhoid fever.

PubMed

Bhan, Maharaj K; Bahl, Rajiv; Sazawal, Sunil; Sinha, Anju; Kumar, Ramesh; Mahalanabis, Dilip; Clemens, John D

2002-12-15

Helicobacter pylori infection has been reported to increase the risk of cholera. This nested case-control study was conducted to determine whether H. pylori infection is associated with occurrence of typhoid fever. Eighty-three case subjects of culture-proven typhoid fever were identified through a 1-year surveillance of subjects aged 0-40 years in an urban slum. Two age- and sex-matched neighborhood control subjects were concurrently selected for each case subject. Serum anti-H. pylori immunoglobulin G antibodies were measured in case and neighborhood control subjects. For determining other risk factors, 2 additional community control subjects per case were selected. There was a significant association between the presence of serum anti-H. pylori immunoglobulin G antibodies and typhoid fever (adjusted odds ratio, 2.03; 95% confidence interval, 1.02-4.01). Illiteracy, being part of a nuclear family, nonuse of soap, and consumption of ice cream were also associated with a significantly greater risk of typhoid fever. This study provides the first empiric evidence that H. pylori infection is associated with an increased risk of typhoid fever.

Autism with intellectual disability related to dynamics of head circumference growth during early infancy.

PubMed

McKeague, Ian W; Brown, Alan S; Bao, Yuanyuan; Hinkka-Yli-Salomäki, Susanna; Huttunen, Jukka; Sourander, Andre

2015-05-01

It is not yet definitively known whether dynamic features of head circumference growth are associated with autism. To address this issue, we carried out a nested matched case-control study using data from national well baby clinics in Finland; autism cases were identified from the Finnish Hospital and Outpatient Discharge Registry. A nonparametric Bayesian method was used to construct growth velocity trajectories between birth and 2 years of age in autism cases and matched control subjects (n = 468 in main analyses, 1:1 matched control subjects). Estimates of odds ratios for autism risk in relation to the growth velocities were obtained using conditional logistic regression. Growth velocity of head circumference at 3 months of age, adjusting for gestational age at birth and maternal age, is significantly associated with autism (p = .014); the finding was observed in subjects with comorbid intellectual disability (ID) (p = .025) but not in those without ID (p = .15). Height growth velocity among subjects with autism and without ID is significantly associated with autism at 6 months (p = .007), and weight growth velocity at 18 months without ID (p = .02) and 24 months without ID (p = .042) and with ID (p = .037). Acceleration in head circumference growth is associated with autism with comorbid ID at 3 months but not subsequently. This association is unrelated to acceleration in height and weight, which are not strongly associated with autism until after 6 months. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

Lung cancer among newspaper printers exposed to ink mist: a study of trade union members in Manchester, England.

PubMed Central

Leon, D A; Thomas, P; Hutchings, S

1994-01-01

A nested case-control study of lung cancer among men exposed to ink mist in newspaper production with rotary letterpress technology is presented. It is based within a historical cohort of 9232 printing workers in Manchester (1949-63). Men who operated newspaper rotary letterpress machines had a lung cancer standardised mortality ratio (SMR) of 179 (95% confidence interval (95% CI) 144-218) when compared with rates for England and Wales for the follow up period 1950-83. When adjustment was made for the higher rates in the local area, the SMR was reduced to 122 (95% CI 98-148). The nested case control study was based on 110 lung cancer cases (1949-86) and 316 matched controls. Duration of work in a rotary letterpress machine room was positively associated with risk of lung cancer (chi 2 linear trend = 3.30, p = 0.07); mean with 30 or more years duration of exposure had a risk of 1.73 (95% CI 0.94-3.17), relative to those with less than 20 years of exposure. Adjustment for period of first exposure in a machine room reduced the strength of the positive duration effect. The magnitude of the SMRs found in the cohort study could be explained by confounding with smoking. The duration effect seen in the case-control study, however, suggests that there may be a real effect of exposure to letterpress ink mists. This is biologically plausible, as benzo[a]pyrene, a known human carcinogen, has been found in appreciable concentrations in the atmosphere of rotary letterpress machine rooms. PMID:8111469

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.

Alcohol and Difficulty Conceiving in the SUN Cohort: A Nested Case-Control Study.

PubMed

Lopez-del Burgo, Cristina; Gea, Alfredo; de Irala, Jokin; Martínez-González, Miguel A; Chavarro, Jorge E; Toledo, Estefania

2015-07-27

The role of alcohol on fertility remains unclear. We aimed to investigate the association between alcohol and specific alcoholic beverages consumption and the risk of difficulty getting pregnant. We used a case-control study nested within the Seguimiento Universidad de Navarra (SUN) cohort, a prospective, dynamic and multipurpose cohort of 21,705 Spanish university graduates, followed biennially with mailed questionnaires. We identified 686 case-control pairs, matched for age and time in the cohort. Cases were women reporting difficulty getting pregnant. Controls did not consult due to difficulty conceiving and had at least one child during follow-up. After adjustment for potential confounders, we found no association between self-reported difficulty getting pregnant and the number of alcoholic beverages consumed per week, (Odds Ratio [OR] > 5 drinks/week vs. none = 1.04, 95% Confidence Interval [CI] = 0.72-1.51). No association between types of alcoholic beverage and difficulty conceiving (OR > 5 drinks of wine/week vs. none = 1.16, 95% CI = 0.72-1.88; OR > 5 drinks of beer/week vs. none = 1.06, 95% CI = 0.82-1.37; OR > 5 drinks of spirits/week vs. none = 1.24, 95% CI = 0.84-1.64) was observed. In conclusion, we found no association between alcohol intake and risk of consulting a physician due to difficulty conceiving. More studies are needed to clearly elucidate the effects of alcohol intake on women's fertility. In the meantime, recommendations about alcohol intake to couples trying to conceive have to be given cautiously.

Alcohol and Difficulty Conceiving in the SUN Cohort: A Nested Case-Control Study

PubMed Central

Lopez-del Burgo, Cristina; Gea, Alfredo; de Irala, Jokin; Martínez-González, Miguel A.; Chavarro, Jorge E.; Toledo, Estefania

2015-01-01

The role of alcohol on fertility remains unclear. We aimed to investigate the association between alcohol and specific alcoholic beverages consumption and the risk of difficulty getting pregnant. We used a case-control study nested within the Seguimiento Universidad de Navarra (SUN) cohort, a prospective, dynamic and multipurpose cohort of 21,705 Spanish university graduates, followed biennially with mailed questionnaires. We identified 686 case-control pairs, matched for age and time in the cohort. Cases were women reporting difficulty getting pregnant. Controls did not consult due to difficulty conceiving and had at least one child during follow-up. After adjustment for potential confounders, we found no association between self-reported difficulty getting pregnant and the number of alcoholic beverages consumed per week, (Odds Ratio [OR] > 5 drinks/week vs. none = 1.04, 95% Confidence Interval [CI] = 0.72–1.51). No association between types of alcoholic beverage and difficulty conceiving (OR > 5 drinks of wine/week vs. none = 1.16, 95% CI = 0.72–1.88; OR > 5 drinks of beer/week vs. none = 1.06, 95% CI = 0.82–1.37; OR > 5 drinks of spirits/week vs. none = 1.24, 95% CI = 0.84–1.64) was observed. In conclusion, we found no association between alcohol intake and risk of consulting a physician due to difficulty conceiving. More studies are needed to clearly elucidate the effects of alcohol intake on women’s fertility. In the meantime, recommendations about alcohol intake to couples trying to conceive have to be given cautiously. PMID:26225997

Infections and the risk of incident giant cell arteritis: a population-based, case-control study.

PubMed

Rhee, Rennie L; Grayson, Peter C; Merkel, Peter A; Tomasson, Gunnar

2017-06-01

Alterations in the immune system and infections are suspected to increase susceptibility to giant cell arteritis (GCA). Recently herpes zoster has been directly implicated in the pathogenesis of GCA. We examined the association between prior infections, in particular herpes zoster, and incident GCA in a population-based cohort. A nested case-control study was performed using an electronic database from the UK. Cases with newly diagnosed GCA were identified using a validated algorithm and compared with age-matched, sex-matched and practice-matched controls. Conditional logistic regression was used to examine the relationship between any infection or herpes zoster infection on the development of GCA after adjusting for potential confounders; results were expressed as incidence rate ratios (IRRs). There were 4559 cases of GCA and 22 795 controls. Any prior infection and herpes zoster were associated with incident GCA (IRR 1.26 (95% CI 1.16 to 1.36), p<0.01; and 1.17 (95% CI 1.04 to 1.32), p<0.01, respectively). A greater number of infections was associated with a higher risk of developing GCA (IRR for 1, 2-4 and ≥5 infections was 1.28, 1.60 and 2.18, respectively). Antecedent infections and, to a lesser extent, herpes zoster infections are modestly associated with incident GCA. These data provide population-level support for the hypothesis that long-standing alterations of the immune system are associated with susceptibility to GCA and suggest that herpes zoster is unlikely to play a major causal role in the pathogenesis of GCA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Diet-related risk factors for gastric dilatation-volvulus in dogs of high-risk breeds.

PubMed

Raghavan, Malathi; Glickman, Nita; McCabe, George; Lantz, Gary; Glickman, Lawrence T

2004-01-01

A nested case-control study was conducted among 1634 dogs with complete diet information in a 5-year prospective study to determine diet-related risk factors for gastric dilatation-volvulus (GDV). Cases included 106 dogs that developed GDV; controls included 212 dogs without GDV that were frequency matched to cases by year of GDV onset. Proportionate energy consumed from major food types and from carbohydrates was determined. Dogs were categorized as consuming either a low volume or high volume of food based on the median number of cups of food fed per kg of body weight per meal. Dogs fed a larger volume of food per meal were at a significantly (P<0.05) increased risk of GDV, regardless of the number of meals fed daily. For both large- and giant-breed dogs, the risk of GDV was highest for dogs fed a larger volume of food once daily.

Risk of Gambling Disorder and Impulse Control Disorder With Aripiprazole, Pramipexole, and Ropinirole: A Pharmacoepidemiologic Study.

PubMed

Etminan, Mahyar; Sodhi, Mohit; Samii, Ali; Procyshyn, Ric M; Guo, Michael; Carleton, Bruce C

2017-02-01

Recently, the US Food and Drug Administration issued a warning regarding the potential risk of gambling disorder, but large epidemiologic studies are lacking. We used a large health claims database from the United States and conducted a nested case-control study. Cases were defined as subjects newly diagnosed with gambling disorder or impulse control disorder. For each case, 10 controls were selected and matched to cases by age and follow-up time and calendar time. Adjusted rate ratios were computed with conditional logistic regression. There are 355 cases of gambling disorder and 3550 controls along with 4341 cases of impulse control disorder and 43,410 corresponding controls. After adjusting for confounders, users of aripiprazole demonstrated an increased risk of pathologic gambling (rate ratio [RR], 5.23; 95% confidence interval [CI], 1.78-15.38) and impulse control disorder (RR, 7.71; 95% CI, 5.81-10.34). The risk was also elevated for pramipexole or ropinirole for both gambling disorder and impulse control disorder (RR, 7.61; 95% CI, 2.75-21.07; RR, 3.28; 95% CI, 2.31-4.66, respectively). Our study confirms an association between aripiprazole, pramipexole, or ropinirole and impulse control disorder and gambling disorder.

Complications of ventilation tube insertion in children with and without cleft palate: a nested case-control comparison.

PubMed

Smillie, Ian; Robertson, Sophie; Yule, Anna; Wynne, David M; Russell, Craig J H

2014-10-01

Optimizing hearing in patients with cleft lip and/or palate (CLP) by early recognition and management of otitis media with effusion is essential for speech development. Some evidence has suggested higher complication rates from ventilation tube (VT) insertion in patients with CLP and has led to a trend not to treat these patients surgically. However, studies have failed to match comparison groups for age and sex. To compare complication rates from VT insertion in pediatric patients with and without CLP. The study used a nested case-control design to evaluate 60 pediatric patients with CLP who underwent VT insertion at a children's hospital. The control group of age- and sex-matched patients was selected from a database of 2943 VT insertions. All patients were administered general anesthesia and underwent VT insertion by a pediatric otorhinolaryngology (ENT) team. The primary outcomes were numbers of otorrhea complications. Secondarily, rates of attendance at an ENT clinic specifically for complications were evaluated. Finally, numbers of complications other than otorrhea were assessed but not statistically analyzed owing to the varied types and low numbers in each group. The control cohort had 151 documented cases of otorrhea compared with 121 in the CLP group (ratio 1.25:1); the difference between groups was not statistically significant (P = .52). There was no significant difference in mean ENT clinic visits per patient for complications between groups (0.80 in the CLP group, 0.78 for controls) (P = .66). Regarding complications other than otorrhea, the control group reported more than the CLP group (43 vs 25; ratio, 1.7:1). Complication rates of VT placement among patients with CLP were not higher than those among patients without CLP. Therefore, treatment with VT insertion should be administered to patients with CLP under the same guidelines as for those without CLP. Indeed, there could be an argument for a shift in practice toward more aggressive treatment of patients with CLP, who are already vulnerable to speech and social developmental delay.

Eczema in early childhood, sociodemographic factors and lifestyle habits are associated with food allergy: a nested case-control study.

PubMed

Ben-Shoshan, Moshe; Soller, Lianne; Harrington, Daniel W; Knoll, Megan; La Vieille, Sebastian; Fragapane, Joseph; Joseph, Lawrence; St Pierre, Yvan; Wilson, Kathie; Elliott, Susan J; Clarke, Ann E

2015-01-01

Studies suggest an increase in food allergy prevalence over the last decade, but the contributing factors remain unknown. The aim of this study was to evaluate the association between the most common food allergies and atopic history, sociodemographic characteristics and lifestyle habits. We conducted a case-control study nested within the SPAACE study (Surveying Prevalence of Food Allergy in All Canadian Environments) – a cross-Canada, random telephone survey. Cases consisted of individuals with probable food allergy (self-report of convincing symptoms and/or physician diagnosis) to milk, egg, peanut, tree nut, shellfish, fish, wheat, soy, or sesame. Controls consisted of nonallergic individuals, matched for age. Cases and controls were queried on personal and family history of atopy, sociodemographic characteristics and lifestyle habits. Multivariate logistic regression was used to evaluate the association between atopy, sociodemographic characteristics and lifestyle habits with probable food allergy. Between September 2010 and September 2011, 480 cases and 4,950 controls completed the questionnaire. For all 9 allergens, factors associated with a higher risk of probable allergy were as follows: (1) personal history of eczema (in the first 2 years of life), asthma or hay fever (odds ratio, OR 2.3, 95% CI 1.6-3.5; OR 2.8, 95% CI 2.2-3.6, and OR 2.3, 95% CI 1.8-3.0, respectively), (2) maternal, paternal or sibling's food allergy (OR 3.7, 95% CI 2.5-5.6; OR 3.0, 95% CI 1.8-5.1, and OR 3.1, 95% CI 2.2-4.2), (3) high household income (top 20%; OR 1.5, 95% CI 1.2-2.0). Males and older individuals were less likely to have food allergy (OR 0.7, 95% CI 0.6-0.9, and OR 0.99, 95% CI 0.99-1.00). Eczema in the first 2 years of life was the strongest risk factor for egg, peanut, tree nut and fish allergy. This is the largest population-based nested case-control study exploring factors associated with food allergies. Our results reveal that, in addition to previously reported factors, eczema in the first 2 years of life is consistently associated with food allergies. © 2015 S. Karger AG, Basel.

A Statewide Nested Case-Control Study of Preterm Birth and Air Pollution by Source and Composition: California, 2001-2008.

PubMed

Laurent, Olivier; Hu, Jianlin; Li, Lianfa; Kleeman, Michael J; Bartell, Scott M; Cockburn, Myles; Escobedo, Loraine; Wu, Jun

2016-09-01

Preterm birth (PTB) has been associated with exposure to air pollution, but it is unclear whether effects might vary among air pollution sources and components. We studied the relationships between PTB and exposure to different components of air pollution, including gases and particulate matter (PM) by size fraction, chemical composition, and sources. Fine and ultrafine PM (respectively, PM2.5 and PM0.1) by source and composition were modeled across California over 2000-2008. Measured PM2.5, nitrogen dioxide, and ozone concentrations were spatially interpolated using empirical Bayesian kriging. Primary traffic emissions at fine scale were modeled using CALINE4 and traffic indices. Data on maternal characteristics, pregnancies, and birth outcomes were obtained from birth certificates. Associations between PTB (n = 442,314) and air pollution exposures defined according to the maternal residence at birth were examined using a nested matched case-control approach. Analyses were adjusted for maternal age, race/ethnicity, education and neighborhood income. Adjusted odds ratios for PTB in association with interquartile range (IQR) increases in average exposure during pregnancy were 1.133 (95% CI: 1.118, 1.148) for total PM2.5, 1.096 (95% CI: 1.085, 1.108) for ozone, and 1.079 (95% CI: 1.065, 1.093) for nitrogen dioxide. For primary PM, the strongest associations per IQR by source were estimated for onroad gasoline (9-11% increase), followed by onroad diesel (6-8%) and commercial meat cooking (4-7%). For PM2.5 composition, the strongest positive associations per IQR were estimated for nitrate, ammonium, and secondary organic aerosols (11-14%), followed by elemental and organic carbon (2-4%). Associations with local traffic emissions were positive only when analyses were restricted to births with residences geocoded at the tax parcel level. In our statewide nested case-control study population, exposures to both primary and secondary pollutants were associated with an increase in PTB. Laurent O, Hu J, Li L, Kleeman MJ, Bartell SM, Cockburn M, Escobedo L, Wu J. 2016. A statewide nested case-control study of preterm birth and air pollution by source and composition: California, 2001-2008. Environ Health Perspect 124:1479-1486; http://dx.doi.org/10.1289/ehp.1510133.

Association between cardiovascular events and sodium-containing effervescent, dispersible, and soluble drugs: nested case-control study

PubMed Central

George, Jacob; Majeed, Waseem; Mackenzie, Isla S; Wei, Li

2013-01-01

Objective To determine whether patients taking formulations of drugs that contain sodium have a higher incidence of cardiovascular events compared with patients on non-sodium formulations of the same drugs. Design Nested case-control study. Setting UK Primary Care Patients registered on the Clinical Practice Research Datalink (CPRD). Participants All patients aged 18 or over who were prescribed at least two prescriptions of sodium-containing formulations or matched standard formulations of the same drug between January 1987 and December 2010. Main outcome measures Composite primary outcome of incident non-fatal myocardial infarction, incident non-fatal stroke, or vascular death. We performed 1:1 incidence density sampling matched controls using the UK Clinical Practice Research Datalink (CPRD). For the secondary analyses, cases were patients with the individual components of the primary study composite endpoint of hypertension, incident heart failure, and all cause mortality. Results 1 292 337 patients were included in the study cohort. Mean follow-up time was 7.23 years. A total of 61 072 patients with an incident cardiovascular event were matched with controls. For the primary endpoint of incident non-fatal myocardial infarction, incident non-fatal stroke, or vascular death the adjusted odds ratio for exposure to sodium-containing drugs was 1.16 (95% confidence interval 1.12 to 1.21). The adjusted odds ratios for the secondary endpoints were 1.22 (1.16 to 1.29) for incident non-fatal stroke, 1.28 (1.23 to 1.33) for all cause mortality, 7.18 (6.74 to 7.65) for hypertension, 0.98 (0.93 to 1.04) for heart failure, 0.94 (0.88 to 1.00) for incident non-fatal myocardial infarction, and 0.70 (0.31 to 1.59) for vascular death. The median time from date of first prescription (that is, date of entry into cohort) to first event was 3.92 years. Conclusions Exposure to sodium-containing formulations of effervescent, dispersible, and soluble medicines was associated with significantly increased odds of adverse cardiovascular events compared with standard formulations of those same drugs. Sodium-containing formulations should be prescribed with caution only if the perceived benefits outweigh these risks. PMID:24284017

Aetiology of childhood pneumonia in a well vaccinated South African birth cohort: a nested case-control study of the Drakenstein Child Health Study.

PubMed

Zar, Heather J; Barnett, Whitney; Stadler, Attie; Gardner-Lubbe, Sugnet; Myer, Landon; Nicol, Mark P

2016-06-01

Pneumonia is a leading cause of mortality and morbidity in children globally. The cause of pneumonia after introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) has not been well studied in low-income and middle-income countries, and most data are from cross-sectional studies of children admitted to hospital. We aimed to longitudinally investigate the incidence and causes of childhood pneumonia in a South African birth cohort. We did a nested case-control study of children in the Drakenstein Child Health Study who developed pneumonia from May 29, 2012, to Dec 1, 2014. Children received immunisations including acellular pertussis vaccine and PCV13. A nested subgroup had nasopharyngeal swabs collected every 2 weeks throughout infancy. We identified pneumonia episodes and collected blood, nasopharyngeal swabs, and induced sputum specimens. We used multiplex real-time PCR to detect pathogens in nasopharyngeal swabs and induced sputum of pneumonia cases and in nasopharyngeal swabs of age-matched and site-matched controls. To show associations between organisms and pneumonia we used conditional logistic regression; results are presented as odds ratios (ORs) with 95% CIs. 314 pneumonia cases occurred (incidence of 0·27 episodes per child-year, 95% CI 0·24-0·31; median age 5 months [IQR 3-9]) in 967 children during 1145 child-years of follow-up. 60 (21%) cases of pneumonia were severe (incidence 0·05 episodes per child-year [95% CI 0·04-0·07]) with a case fatality ratio of 1% (three deaths). A median of five organisms (IQR 4-6) were detected in cases and controls with nasopharyngeal swabs, and a median of six organisms (4-7) recorded in induced sputum (p=0·48 compared with nasopharyngeal swabs). Bordetella pertussis (OR 11·08, 95% CI 1·33-92·54), respiratory syncytial virus (8·05, 4·21-15·38), or influenza virus (4·13, 2·06-8·26) were most strongly associated with pneumonia; bocavirus, adenovirus, parainfluenza virus, Haemophilus influenzae, and cytomegalovirus were also associated with pneumonia. In cases, testing of induced sputum in addition to nasopharyngeal swabs provided incremental yield for detection of B pertussis and several viruses. Pneumonia remains common in this highly vaccinated population. Respiratory syncytial virus was the most frequently detected pathogen associated with pneumonia; influenza virus and B pertussis were also strongly associated with pneumonia. Testing of induced sputum increases the yield for detection of several organisms. New vaccines and strategies are needed to address the burden of childhood pneumonia. Bill & Melinda Gates Foundation, Medical Research Council South Africa, National Research Foundation South Africa, National Institute of Health, and H3Africa. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fatal injuries in the slums of Nairobi and their risk factors: results from a matched case-control study.

PubMed

Ziraba, Abdhalah Kasiira; Kyobutungi, Catherine; Zulu, Eliya Msiyaphazi

2011-06-01

Injuries contribute significantly to the rising morbidity and mortality attributable to non-communicable diseases in the developing world. Unfortunately, active injury surveillance is lacking in many developing countries, including Kenya. This study aims to describe and identify causes of and risk factors for fatal injuries in two slums in Nairobi city using a demographic surveillance system framework. The causes of death are determined using verbal autopsies. We used a nested case-control study design with all deaths from injuries between 2003 and 2005 as cases. Two controls were randomly selected from the non-injury deaths over the same period and individually matched to each case on age and sex. We used conditional logistic regression modeling to identity individual- and community-level factors associated with fatal injuries. Intentional injuries accounted for about 51% and unintentional injuries accounted for 49% of all injuries. Homicides accounted for 91% of intentional injuries and 47% of all injury-related deaths. Firearms (23%) and road traffic crashes (22%) were the leading single causes of deaths due to injuries. About 15% of injuries were due to substance intoxication, particularly alcohol, which in this community comes from illicit brews and is at times contaminated with methanol. Results suggest that in the pervasively unsafe and insecure environment that characterizes the urban slums, ethnicity, residence, and area level factors contribute significantly to the risk of injury-related mortality.

Biomarkers and Bacterial Pneumonia Risk in Patients with Treated HIV Infection: A Case-Control Study

PubMed Central

Bjerk, Sonja M.; Baker, Jason V.; Emery, Sean; Neuhaus, Jacqueline; Angus, Brian; Gordin, Fred M.; Pett, Sarah L.; Stephan, Christoph; Kunisaki, Ken M.

2013-01-01

Background Despite advances in HIV treatment, bacterial pneumonia continues to cause considerable morbidity and mortality in patients with HIV infection. Studies of biomarker associations with bacterial pneumonia risk in treated HIV-infected patients do not currently exist. Methods We performed a nested, matched, case-control study among participants randomized to continuous combination antiretroviral therapy (cART) in the Strategies for Management of Antiretroviral Therapy trial. Patients who developed bacterial pneumonia (cases) and patients without bacterial pneumonia (controls) were matched 1∶1 on clinical center, smoking status, age, and baseline cART use. Baseline levels of Club Cell Secretory Protein 16 (CC16), Surfactant Protein D (SP-D), C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer were compared between cases and controls. Results Cases (n = 72) and controls (n = 72) were 25.7% female, 51.4% black, 65.3% current smokers, 9.7% diabetic, 36.1% co-infected with Hepatitis B/C, and 75.0% were on cART at baseline. Median (IQR) age was 45 (41, 51) years with CD4+ count of 553 (436, 690) cells/mm3. Baseline CC16 and SP-D were similar between cases and controls, but hsCRP was significantly higher in cases than controls (2.94 µg/mL in cases vs. 1.93 µg/mL in controls; p = 0.02). IL-6 and d-dimer levels were also higher in cases compared to controls, though differences were not statistically significant (p-value 0.06 and 0.10, respectively). Conclusions In patients with cART-treated HIV infection, higher levels of systemic inflammatory markers were associated with increased bacterial pneumonia risk, while two pulmonary-specific inflammatory biomarkers, CC16 and SP-D, were not associated with bacterial pneumonia risk. PMID:23457535

Effect of Tubal Sterilization Technique on Risk of Serous Ovarian and Primary Peritoneal Carcinoma

PubMed Central

LESSARD-ANDERSON, Collette R.; HANDLOGTEN, Kathryn S.; MOLITOR, Rochelle J.; DOWDY, Sean C.; CLIBY, William A.; WEAVER, Amy L.; SAUVER, Jennifer ST.; BAKKUM-GAMEZ, Jamie N.

2014-01-01

Objective To determine the effect of excisional tubal sterilization on subsequent development of serous epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC). Methods We performed a population-based, nested case-control study using the Rochester Epidemiology Project. We identified all patients with a diagnosis of serous EOC or PPC from 1966 through 2009. Each case was age-matched to 2 controls without either diagnosis. Odds ratios (ORs) and corresponding 95% CIs were estimated from conditional logistic regression models. Models were adjusted for prior hysterectomy, prior salpingo-oophorectomy, oral contraceptive use, endometriosis, infertility, gravidity, and parity. Results In total, we identified 194 cases of serous EOC and PPC during the study period and matched them with 388 controls (mean [SD] age, 61.4 [15.2] years). Fourteen cases (7.2%) and 46 controls (11.9%) had undergone tubal sterilization. Adjusted risk of serous EOC or PPC was slightly lower after any tubal sterilization (OR, 0.59 [95% CI, 0.29–1.17]; P=.13). The rate of excisional tubal sterilization was lower in cases than controls (2.6% vs 6.4%). Adjusted risk of serous EOC and PPC was decreased by 64% after excisional tubal sterilization (OR, 0.36 [95% CI, 0.13–1.02]; P=.054) compared with those without sterilization or with nonexcisional tubal sterilization. Conclusions We present a population-based investigation of the effects of excisional tubal sterilization on the risk of serous EOC and PPC. Excisional methods may confer greater risk reduction than other sterilization methods. PMID:25316178

Association between medication prescription for atopic diseases and attention-deficit/hyperactivity disorder.

PubMed

van der Schans, Jurjen; Pleiter, Janine C; de Vries, Tjalling W; Schuiling-Veninga, Catharina C M; Bos, Jens H J; Hoekstra, Pieter J; Hak, Eelko

2016-08-01

Data on the association between atopic diseases and attention-deficit/hyperactivity disorder (ADHD) have been inconclusive. To assess whether children with drug-treated ADHD are more likely to receive treatment for asthma, allergic rhinitis, or eczema before the start of ADHD medication use compared with controls and to examine the effect of parents receiving medication for ADHD and atopic diseases on ADHD medication use in their offspring. We conducted a retrospective nested case-control study among children (6-12 years of age) using the Groningen University prescription database. Cases were defined as children with at least 2 prescriptions of methylphenidate within 12 months. For each case, 4 controls were matched on age, sex, and regional area code. Parental prescription data were linked to cases and controls to assess the influence of parents receiving medication for ADHD and atopic diseases on ADHD medication use in their offspring. We identified 4257 cases and 17,028 matched controls. Drug treatment for asthma, allergic rhinitis, and eczema was more common in cases than controls (adjusted odds ratios [aORs], 1.4 [95% confidence interval (CI), 1.3-1.6], 1.4 [95% CI, 1.1-1.8], and 1.3 [95% CI, 1.1-1.5], respectively). Medication for allergic rhinitis and asthma among parents was associated with ADHD treatment in their children (aORs, 1.3 [95% CI, 1.1-1.5] and 1.2 [95% CI, 1.1-1.3], respectively). This study provides further evidence to support the hypothesis that atopic diseases are associated with ADHD. The parental-offspring association suggests a possible genetic and/or environmental component. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Acute Myocardial Infarction Risk in Patients with Coronary Artery Disease Doubled after Upper Gastrointestinal Tract Bleeding: A Nationwide Nested Case-Control Study.

PubMed

Wu, Chia-Jung; Lin, Hung-Jung; Weng, Shih-Feng; Hsu, Chien-Chin; Wang, Jhi-Joung; Su, Shih-Bin; Huang, Chien-Cheng; Guo, How-Ran

2015-01-01

Prior studies of upper gastrointestinal bleeding (UGIB) and acute myocardial infarction (AMI) are small, and long-term effects of UGIB on AMI have not been delineated. We investigated whether UGIB in patients diagnosed with coronary artery disease (CAD) increased their risk of subsequent AMI. This was a population-based, nested case-control study using Taiwan's National Health Insurance Research Database. After propensity-score matching for age, gender, comorbidities, CAD date, and follow-up duration, we identified 1,677 new-onset CAD patients with AMI (AMI[+]) between 2001 and 2006 as the case group and 10,062 new-onset CAD patients without (AMI[-]) as the control group. Conditional logistic regression was used to examine the association between UGIB and AMI. Compared with UGIB[-] patients, UGIB[+] patients had twice the risk for subsequent AMI (adjusted odds ratio [AOR] = 2.08; 95% confidence interval [CI], 1.72-2.50). In the subgroup analysis for gender and age, UGIB[+] women (AOR = 2.70; 95% CI, 2.03-3.57) and patients < 65 years old (AOR = 2.23; 95% CI, 1.56-3.18) had higher odds of an AMI. UGIB[+] AMI[+] patients used nonsignificantly less aspirin than did UGIB[-] AMI[+] patients (27.69% vs. 35.61%, respectively). UGIB increased the risk of subsequent AMI in CAD patients, especially in women and patients < 65. This suggests that physicians need to use earlier and more aggressive intervention to detect UGIB and prevent AMI in CAD patients.

Occupational kidney disease among Chinese herbalists exposed to herbs containing aristolochic acids.

PubMed

Yang, Hsiao-Yu; Wang, Jung-Der; Lo, Tsai-Chang; Chen, Pau-Chung

2011-04-01

Many Chinese herbs contain aristolochic acids (ALAs) which are nephrotoxic and carcinogenic. The objective of this study was to identify whether exposure to herbs containing ALAs increased the risk of kidney disease among Chinese herbalists. A nested case-control study was carried out on 6538 Chinese herbalists registered between 1985 and 1998. All incident cases of chronic renal failure reported to the Database of Catastrophic Illness of the National Health Insurance Bureau between 1995 and 2000 were defined as the case group. Up to four controls without renal failure were randomly matched to each case by sex and year of birth. A structured questionnaire survey was administered between November and December 2002. The Mantel-Haenszel method and conditional logistic regression were used to estimate the risks. 40 cases and 98 matched controls were included in the final analysis. After adjusting for age, frequent analgesic use, and habitual consumption of alcohol, fermented or smoked food, we found manufacturing and selling Chinese herbal medicine (OR 3.43, 95% CI 1.16 to 10.19), processing, selling or dispensing herbal medicines containing Fangji (OR 4.17, 95% CI 1.36 to 12.81), living in the workplace (OR 3.14, 95% CI 1.11 to 8.84) and a history of taking of herbal medicines containing Fangji (frequently or occasionally) (OR 5.42, 95% CI 1.18 to 24.96) were significantly associated with renal failure. Occupational exposure to and consumption of herbs containing ALAs increases the risk of renal failure in Chinese herbalists.

Mercury exposure and risk of cardiovascular disease: a nested case-control study in the PREDIMED (PREvention with MEDiterranean Diet) study.

PubMed

Downer, Mary K; Martínez-González, Miguel A; Gea, Alfredo; Stampfer, Meir; Warnberg, Julia; Ruiz-Canela, Miguel; Salas-Salvadó, Jordi; Corella, Dolores; Ros, Emilio; Fitó, Montse; Estruch, Ramon; Arós, Fernando; Fiol, Miquel; Lapetra, José; Serra-Majem, Lluís; Bullo, Monica; Sorli, Jose V; Muñoz, Miguel A; García-Rodriguez, Antonio; Gutierrez-Bedmar, Mario; Gómez-Gracia, Enrique

2017-01-05

Substantial evidence suggests that consuming 1-2 servings of fish per week, particularly oily fish (e.g., salmon, herring, sardines) is beneficial for cardiovascular health due to its high n-3 polyunsaturated fatty acid content. However, there is some concern that the mercury content in fish may increase cardiovascular disease risk, but this relationship remains unclear. The PREDIMED trial included 7477 participants who were at high risk for cardiovascular disease at baseline. In this study, we evaluated associations between mercury exposure, fish consumption and cardiovascular disease. We randomly selected 147 of the 288 cases diagnosed with cardiovascular disease during follow-up and matched them on age and sex to 267 controls. Instrumental neutron activation analysis was used to assess toenail mercury concentration. In-person interviews, medical record reviews and validated questionnaires were used to assess fish consumption and other covariates. Information was collected at baseline and updated yearly during follow-up. We used conditional logistic regression to evaluate associations in the total nested case-control study, and unconditional logistic regression for population subsets. Mean (±SD) toenail mercury concentrations (μg per gram) did not significantly differ between cases (0.63 (±0.53)) and controls (0.67 (±0.49)). Mercury concentration was not associated with cardiovascular disease in any analysis, and neither was fish consumption or n-3 fatty acids. The fully-adjusted relative risks for the highest versus lowest quartile of mercury concentration were 0.71 (95% Confidence Interval [CI], 0.34, 1.14; p trend  = 0.37) for the nested case-control study, 0.74 (95% CI, 0.32, 1.76; p trend  = 0.43) within the Mediterranean diet intervention group, and 0.50 (95% CI, 0.13, 1.96; p trend  = 0.41) within the control arm of the trial. Associations remained null when mercury was jointly assessed with fish consumption at baseline and during follow-up. Results were similar in different sensitivity analyses. We found no evidence that mercury exposure from regular fish consumption increases cardiovascular disease risk in a population of Spanish adults with high cardiovascular disease risk and high fish consumption. This implies that the mercury content in fish does not detract from the already established cardiovascular benefits of fish consumption. ISRCTN35739639 .

Anticholinergic Exposure and Risk of Pneumonia in Persons with Alzheimer's Disease: A Nested Case-Control Study.

PubMed

Lampela, Pasi; Tolppanen, Anna-Maija; Tanskanen, Antti; Tiihonen, Jari; Hartikainen, Sirpa; Taipale, Heidi

2017-01-01

Risk of pneumonia is increased in persons with Alzheimer's disease (AD). In some studies, anticholinergic drugs (AC) have been associated with an increased pneumonia risk. We analyzed the risk of pneumonia associated with ACs in persons with AD. We performed a nested case-control study using register-based data from a Finnish nationwide MEDALZ cohort including all community-dwelling persons diagnosed with AD during 2005-2011. Cases were identified based on pneumonia diagnoses (n = 12,442) from hospital discharge and causes of death registers. Up to two controls without pneumonia were matched based on time since AD diagnoses, age, and gender for each case; AC use was measured using Anticholinergic Drug Scale. Use of AC was associated with an increased risk of pneumonia (adjusted odds ratio (OR) 1.36, 95% confidence interval (CI) 1.29-1.43). However, there was no increased pneumonia risk in persons using level 3 ACs. Incident use was associated with higher risk of pneumonia (OR 2.68, 95% CI 2.15-3.34) than prevalent use (OR 1.48, 95% CI 1.40-1.57). Among persons using cholinesterase inhibitors (AChEIs), risk of pneumonia was increased in persons using also ACs (OR 1.53, 95% CI 1.41-1.66). ACs were associated with an increased risk of pneumonia in persons with AD, especially at the time of initiation of these drugs. AC use was associated with increased pneumonia risk also in persons using AChEIs. This risk should be carefully considered when treating AD patients.

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

The Role of Healthy Lifestyle in the Implementation of Regressing Suboptimal Health Status among College Students in China: A Nested Case-Control Study

PubMed Central

Chen, Jieyu; Xiang, Hongjie; Jiang, Pingping; Yu, Lin; Jing, Yuan; Li, Fei; Wu, Shengwei; Fu, Xiuqiong; Liu, Yanyan; Kwan, Hiuyee; Luo, Ren; Zhao, Xiaoshan; Sun, Xiaomin

2017-01-01

Background: Suboptimal health status (SHS) is the intermediate health state between health and disease, it is medically undiagnosed and is also termed functional somatic syndrome. Although its clinical manifestations are complicated and various, SHS has not reached the disease status. Unhealthy lifestyle is associated with many chronic diseases and mortality. In accordance with the impact of lifestyle on health, it is intriguing to determine the association between unhealthy lifestyle and SHS risk. Methods: We conducted a nested case-control study among healthy Chinese college students from March 2012 to September 2013, which was nested in a prospective cohort of 5676 students. We performed 1:1 incidence density sampling with matched controls for birth year, sex, grade, specialty and individual character. SHS was evaluated using the medical examination report and Sub-health Measurement Scale V1.0 (SHMS V1.0). Exposure was defined as an unhealthy lifestyle per the frequency of six behavioral dimensions from the Health-promoting Lifestyle Profile (HPLP-II). Results: We matched 543 cases of SHS (42.66%) in a cohort of 1273 students during the 1.5 years mean follow-up time with controls. A significant difference (t = 9.79, p < 0.001) and a reduction in HPLP-II total score was present at 1.5 years follow-up (135.93 ± 17.65) compared to baseline (144.48 ± 18.66). A level-response effect was recorded with an increase of the total HPLP-II (every dimension was correlated with a decreased SHS risk). Compared to respondents with the least exposure (excellent level), those reporting a general HPLP-II level were approximately 2.3 times more likely to develop SHS (odd ratio = 2.333, 95% CI = 1.471 to 3.700); and those with less HPLP-II level (good level) were approximately 1.6 times more likely (1.644, 1.119–2.414) to develop SHS (p < 0.05). Our data indicated that unhealthy lifestyle behavior with respect to behavioral dimensions significantly affected SHS likelihood. Further analyses revealed a marked increase (average increased 14.73 points) in lifestyle level among those SHS regression to health after 1.5 years, with respect to the HPLP-II behavioral dimensions, in addition to the total score (t = −15.34, p < 0.001). Conclusions: SHS is highly attributable to unhealthy lifestyles, and the mitigation of modifiable lifestyle risk factors may lead to SHS regression. Increased efforts to modify unhealthy lifestyles are necessary to prevent SHS. PMID:28264509

The Role of Healthy Lifestyle in the Implementation of Regressing Suboptimal Health Status among College Students in China: A Nested Case-Control Study.

PubMed

Chen, Jieyu; Xiang, Hongjie; Jiang, Pingping; Yu, Lin; Jing, Yuan; Li, Fei; Wu, Shengwei; Fu, Xiuqiong; Liu, Yanyan; Kwan, Hiuyee; Luo, Ren; Zhao, Xiaoshan; Sun, Xiaomin

2017-02-28

Suboptimal health status (SHS) is the intermediate health state between health and disease, it is medically undiagnosed and is also termed functional somatic syndrome. Although its clinical manifestations are complicated and various, SHS has not reached the disease status. Unhealthy lifestyle is associated with many chronic diseases and mortality. In accordance with the impact of lifestyle on health, it is intriguing to determine the association between unhealthy lifestyle and SHS risk. We conducted a nested case-control study among healthy Chinese college students from March 2012 to September 2013, which was nested in a prospective cohort of 5676 students. We performed 1:1 incidence density sampling with matched controls for birth year, sex, grade, specialty and individual character. SHS was evaluated using the medical examination report and Sub-health Measurement Scale V1.0 (SHMS V1.0). Exposure was defined as an unhealthy lifestyle per the frequency of six behavioral dimensions from the Health-promoting Lifestyle Profile (HPLP-II). We matched 543 cases of SHS (42.66%) in a cohort of 1273 students during the 1.5 years mean follow-up time with controls. A significant difference (t = 9.79, p < 0.001) and a reduction in HPLP-II total score was present at 1.5 years follow-up (135.93 ± 17.65) compared to baseline (144.48 ± 18.66). A level-response effect was recorded with an increase of the total HPLP-II (every dimension was correlated with a decreased SHS risk). Compared to respondents with the least exposure (excellent level), those reporting a general HPLP-II level were approximately 2.3 times more likely to develop SHS (odd ratio = 2.333, 95% CI = 1.471 to 3.700); and those with less HPLP-II level (good level) were approximately 1.6 times more likely (1.644, 1.119-2.414) to develop SHS (p < 0.05). Our data indicated that unhealthy lifestyle behavior with respect to behavioral dimensions significantly affected SHS likelihood. Further analyses revealed a marked increase (average increased 14.73 points) in lifestyle level among those SHS regression to health after 1.5 years, with respect to the HPLP-II behavioral dimensions, in addition to the total score (t = -15.34, p < 0.001). SHS is highly attributable to unhealthy lifestyles, and the Int. J. Environ. Res. Public Health 2017, 14, 240 2 of 17 mitigation of modifiable lifestyle risk factors may lead to SHS regression. Increased efforts to modify unhealthy lifestyles are necessary to prevent SHS.

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.

Solving LR Conflicts Through Context Aware Scanning

NASA Astrophysics Data System (ADS)

Leon, C. Rodriguez; Forte, L. Garcia

2011-09-01

This paper presents a new algorithm to compute the exact list of tokens expected by any LR syntax analyzer at any point of the scanning process. The lexer can, at any time, compute the exact list of valid tokens to return only tokens in this set. In the case than more than one matching token is in the valid set, the lexer can resort to a nested LR parser to disambiguate. Allowing nested LR parsing requires some slight modifications when building the LR parsing tables. We also show how LR parsers can parse conflictive and inherently ambiguous languages using a combination of nested parsing and context aware scanning. These expanded lexical analyzers can be generated from high level specifications.

Modest increase in risk of acute coronary syndrome associated with morphine use in cancer patients: a population-based nested case-control study.

PubMed

Lee, Cynthia Wei-Sheng; Muo, Chih-Hsin; Liang, Ji-An; Sung, Fung-Chang; Kao, Chia-Hung

2014-06-01

Morphine is widely used for pain management in cancer patients. Use of heroin, a morphine derivative, is a risk factor for acute coronary syndrome (ACS). This study investigates the risk of ACS associated with morphine use by comparing the incidence of ACS in cancer patients treated with and without morphine. This is a population-based nested case-control study using the Longitudinal Health Insurance Database 2000 in Taiwan. In total, 31,384 patients on the database were diagnosed with cancer without prior history of ACS during 1998-2010. In this cohort, 499 patients subsequently developed ACS and 30,885 patients did not. The 499 patients were designated as the ACS group; controls were selected from the remaining 30,885 patients and matched 3:1 to each case for age, sex, year of cancer diagnosis, and index year. Logistic regression was used to estimate the odds ratios and 95% confidence intervals, and the multivariable model was applied to control for age, sex, and Charlson comorbidity score. Cancer patients who received morphine had a 32% higher risk of developing ACS than non-morphine users. This increase in risk was significant when evaluating the overall cancer patients, but non-significant when evaluating any specific cancer type. The risk of ACS increased significantly with increasing morphine dosage (to ≥65 mg/y). Morphine treatment is associated with a modest increase in risk of ACS in patients with malignancy, but this association displays low significance in specific cancer types. Copyright © 2014 Elsevier Ltd. All rights reserved.

Risk of cancer among HIV-infected patients from a population-based nested case-control study: implications for cancer prevention.

PubMed

Chen, Chang-Hua; Chung, Chih-Yuan; Wang, Li-Hsuan; Lin, Che; Lin, Hsiu-Li; Lin, Hsiu-Chen

2015-03-16

The burden of cancer is likely to increase among the human immunodeficiency virus (HIV)-positive population as it ages due to successful antiretroviral therapy (ART). The purpose of this study was to determine the risk of cancer in HIV-infected patients. This study was a matched nested case-control study. It was performed using the National Health Insurance Research Database of Taiwan. The control group included non-HIV-infected patients matched by sex, age, and year of enrollment. Logistic regression analyses were performed and simultaneously adjusted for potential confounders (income, urbanization, and Charslon index of comorbidity to evaluate HIV infection as an independent risk of cancer. We calculated the overall and sex-specific standardized incidence ratios (SIR) to investigate the pattern of cancer risk and overall cancer risk in the patients with HIV infection. Of the 1,115 HIV-infected patients, 104 (9.33%) developed cancer during the 11-year follow-up period. The risk of cancer for patients with HIV infection was significant (adjusted odds ratio = 3.89, 95% confidence interval [CI] = 2.92-5.19) after adjustment for potential confounders. There was a significantly increased risk of developing non-Hodgkin lymphoma (SIR = 25.73, 95% CI = 6.83-90.85), cervical cancer (SIR = 4.01, 95% CI = 1.0-16.06), lymphoma (SIR = 20.26, 95% CI = 5.86-70.10), and respiratory and intrathoracic cancer (SIR = 20.09, 95% CI = 2.34-172.09) compared with the control group. In addition, HIV-infected patients were at significant risk for renal, oral, breast, liver, skin, and colorectal cancer. Patients with HIV infection are at increased risk for several specific cancers. Our results support the implementation of an active and accelerated cancer screening schedule for patients with HIV infection to increase their life span.

Use of antiepileptic drugs and risk of fractures: case-control study among patients with epilepsy.

PubMed

Souverein, P C; Webb, D J; Weil, J G; Van Staa, T P; Egberts, A C G

2006-05-09

To study the association between use of antiepileptic drugs (AEDs) and risk of fractures. The authors obtained data from the General Practice Research Database (GPRD). A case-control study was nested within a cohort of patients with active epilepsy. Cases were patients with a first fracture after cohort entry. Up to four controls were matched to each case by practice, sex, year of birth, timing of first epilepsy diagnosis, index date, and duration of GPRD history. Cumulative exposure to AEDs was assessed by summing the duration of all AED prescriptions. A distinction was made between AEDs that induce the hepatic cytochrome P-450 enzyme system and AEDs that do not. Medical conditions and drugs known to be associated with bone metabolism or falls were evaluated as potential confounders. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% CIs. The study population comprised 1,018 cases and 1,842 matched controls. The risk of fractures increased with cumulative duration of exposure (p for trend < 0.001), with the strongest association for greater than 12 years of use: adjusted OR 4.15 (95% CI 2.71 to 6.34). Risk estimates were higher in women than in men. There was no difference between users of AEDs that induce and AEDs that do not induce the hepatic cytochrome P-450 system. Long-term use of AEDs was associated with an increased risk of fractures, especially in women. More research on mechanisms of AED-induced bone breakdown and female vulnerability to the effects of AEDs on bone health is warranted.

Socioeconomic status and the risk for being diagnosed with spondyloarthritis and chronic pain: a nested case-control study.

PubMed

Jöud, Anna; Petersson, Ingemar F; Jordan, Kelvin P; Löfvendahl, Sofia; Grahn, Birgitta; Englund, Martin

2014-09-01

Socioeconomic status could potentially impact on which type of rheumatic diagnosis a patient receives. We determined whether different socioeconomic status is a risk factor for being diagnosed with spondyloarthritis (SpA) or chronic pain. In a nested case-control study, we identified two sets of adult cases diagnosed with (i) SpA (n = 1,194) and (ii) chronic pain (n = 3,730) during 2010-2012 in Skåne region, Sweden. We randomly sampled controls matched for age and sex. Level of education, marital status, and income were identified in national registers 4 years before inclusion. We also studied health-care utilization, prescribed pharmaceuticals, and work status. We used conditional logistic regressions and included socioeconomic variables and geographic area in the models. Low (odds ratio [OR] 1.69 95 % CI 1.50-1.91) or moderate education (OR 1.43 95 % CI 1.30-1.57), and low (OR 1.40 95 % CI 1.25-1.57) or moderate income (OR 1.24 95 % CI 1.10-1.38) were associated with a chronic pain diagnosis. For a SpA diagnosis, moderate income (OR 1.25 95 % CI 1.04-1.50) was the only significant factor identified. Both case groups had a larger proportion that did not work (P < 0.001), used more health care (P < 0.001), and were more frequently prescribed NSAIDs (P < 0.001) 4 years before diagnosis than controls. We confirmed that lower levels of education and income are associated with a chronic pain diagnosis. This association may reflect a true higher incidence of chronic pain and/or increased consultation propensity for such pain in people with socioeconomic status. We found no such association for SpA.

Nested Case-control Study of Occupational Radiation Exposure and Breast and Esophagus Cancer Risk among Medical Diagnostic X Ray Workers in Jiangsu of China.

PubMed

Wang, Fu-Ru; Fang, Qiao-Qiao; Tang, Wei-Ming; Xu, Xiao-San; Mahapatra, Tanmay; Mahapatra, Sanchita; Liu, Yu-Fei; Yu, Ning-Le; Sun, Quan-Fu

2015-01-01

Medical diagnostic X-ray workers are one occupational group that expose to the long-term low-dose external radiation over their working lifetime, and they may under risk of different cancers. This study aims to determine the relationship between the occupational X-ray radiation exposure and cancer risk among these workers in Jiangsu, China. We conducted Nested case-control study to investigate the occupational X-ray radiation exposure and cancer risk. Data were collected through self-administered questionnaire, which includes but not limits to demographic data, personal behaviors and family history of cancer. Retrospective dose reconstruction was conducted to estimate the cumulative doses of the x-ray workers. Inferential statistics, t-test and 2 tests were used to compare the differences between each group. We used the logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) of cancer by adjusting the age, gender. All 34 breast cancer cases and 45 esophageal cancer cases that detected in a cohort conducted among health workers between 1950~2011 were included in this presented study, and 158 cancer-free controls were selected by frequency-matched (1:2). Our study found that the occupational radiation exposure was associated with a significantly increased cancer risk compared with the control, especially in breast cancer and esophageal cancer (adjusted OR=2.90, 95% CI: 1.19-7.04 for breast cancer; OR=4.19, 95% CI: 1.87-9.38 for esophageal cancer, and OR=3.43, 95% CI: 1.92-6.12 for total cancer, respectively). The occupational X-ray radiation exposure was associated with increasing cancer risk, which indicates that proper intervention and prevention strategies may be needed in order to bring down the occupational cancer risk.

Daily Intake of Milk Powder and Risk of Celiac Disease in Early Childhood: A Nested Case-Control Study.

PubMed

Hård Af Segerstad, Elin M; Lee, Hye-Seung; Andrén Aronsson, Carin; Yang, Jimin; Uusitalo, Ulla; Sjöholm, Ingegerd; Rayner, Marilyn; Kurppa, Kalle; Virtanen, Suvi M; Norris, Jill M; Agardh, Daniel

2018-04-28

Milk powder and gluten are common components in Swedish infants' diets. Whereas large intakes of gluten early in life increases the risk of celiac disease in genetically at-risk Swedish children, no study has yet evaluated if intake of milk powder by 2 years of age is associated with celiac disease. A 1-to-3 nested case-control study, comprised of 207 celiac disease children and 621 controls matched for sex, birth year, and HLA genotype, was performed on a birth cohort of HLA-DR3-DQ2 and/or DR4-DQ8-positive children. Subjects were screened annually for celiac disease using tissue transglutaminase autoantibodies (tTGA). Three-day food records estimated the mean intake of milk powder at ages 6 months, 9 months, 12 months, 18 months, and 24 months. Conditional logistic regression calculated odds ratios (OR) at last intake prior to seroconversion of tTGA positivity, and for each time-point respectively and adjusted for having a first-degree relative with celiac disease and gluten intake. Intake of milk powder prior to seroconversion of tTGA positivity was not associated with celiac disease (OR = 1.00; 95% CI = 0.99, 1.03; p = 0.763). In conclusion, intake of milk powder in early childhood is not associated with celiac disease in genetically susceptible children.

Investigation of a cluster of pituitary adenomas in workers in the aluminum industry.

PubMed

Cullen, M R; Checkoway, H; Alexander, B H

1996-11-01

Four cases of pituitary adenoma among employees at a primary aluminum production factory were identified over a five year period by a community physician. The objective of this investigation was to determine whether there has been a comparable high incidence in other aluminum factories, and if particular jobs, departments, or activities in the industry are associated with higher rates of the disease. Pituitary adenoma in employees at all United States factories of the company for the years 1989-94 was assessed by a search of a health data information bank and an insurance data base covering present and past employees of the corporation. The incidence in the aluminum workers was estimated and compared with the workers in the index plant. A nested case control study was conducted to compare employment histories of identified cases with those of age and sex matched controls selected from the health information data base. 25 cases, including the index cases, were identified which had been diagnosed during the period 1989-94. The resulting rate of 10.4/100,000 person-years was much lower than that at the index plant. Case-control analysis showed no coherent pattern of location, department, or job significantly associated with risk. In particular, jobs and departments associated with exposures common to aluminum smelting-such as coal tar pitch volatiles and fluorides-were shown to be uncommon among cases compared with age and sex matched controls. Overall, despite the unprecedented cluster at a single plant, no strong evidence was found that the rate of pituitary adenoma is increased in aluminum workers generally. We found no association with any work activity or location in the industry to suggest a work related or exposure related cause for the disease.

User-only design to assess drug effectiveness in clinical practice: application to bisphosphonates and secondary prevention of fractures.

PubMed

Corrao, Giovanni; Ghirardi, Arianna; Segafredo, Giulia; Zambon, Antonella; Della Vedova, Gianluca; Lapi, Francesco; Cipriani, Francesco; Caputi, Achille; Vaccheri, Alberto; Gregori, Dario; Gesuita, Rosaria; Vestri, Annarita; Staniscia, Tommaso; Mazzaglia, Giampiero; Di Bari, Mauro

2014-08-01

Different strategies applicable to control for confounding by indication in observational studies were compared in a large population-based study regarding the effect of bisphosphonates (BPs) for secondary prevention of fractures. The cohort was drawn from healthcare utilization databases of 13 Italian territorial units. Patients aged 55 years or more who were hospitalized for fracture during 2003-2005 entered into the cohort. A nested case-control design was used to compare BPs use in cohort members who did (cases) and who did not experience (controls) a new fracture until 2007 (outcome). Three designs were employed: conventional-matching (D1 ), propensity score-matching (D2 ), and user-only (D3 ) designs. They differed for (i) cohort composition, restricted to patients who received BPs straight after cohort entry (D3 ); (ii) using propensity score for case-control matching (D2 ); and (iii) compared groups of BPs users versus no users (D1 and D2 ) and long-term versus short-term users (D3 ). Bisphosphonate users had odds ratios (95% confidence interval) of 1.20 (1.01 to 1.44) and 0.95 (0.74 to 1.24) by applying D1 and D2 designs, respectively. Statistical evidence that long-term BPs use protects the outcome onset with respect to short-term use was observed for user-only design (D3 ) being the corresponding odds ratio (95% confidence interval) 0.64 (0.44 to 0.93). User-only design yielded closer results to those seen in RCTs. This approach is one possible strategy to account for confounding by indication. Copyright © 2014 John Wiley & Sons, Ltd.

National study of suicide in all people with a criminal justice history.

PubMed

Webb, Roger T; Qin, Ping; Stevens, Hanne; Mortensen, Preben B; Appleby, Louis; Shaw, Jenny

2011-06-01

Previous research has focused on suicide among male prisoners and ex-prisoners, but little is known about risk in the wider offender population. To examine suicide risk over 3 decades among all people processed by a national criminal justice system. Nested case-control study. The whole Danish population. Interlinked national registers identified all adult suicides during 1981 to 2006 according to any criminal justice system contact since 1980. Exposure was defined according to history of criminal justice adjudication, up to and including each subject's last judicial verdict before suicide (or date of matching for controls). There were 27 219 suicides and 524 899 controls matched on age, sex, and time, ie, controls were alive when their matched case died. Suicide. More than a third of all male cases had a criminal justice history, but relative risk against the general population was higher for women than men. Independent effects linked with criminal justice exposure persisted with confounder adjustment. Suicide risk was markedly elevated with custodial sentencing, but the strongest effects were with sentencing to psychiatric treatment and with charges conditionally withdrawn. Risk was raised even in people with a criminal justice history but without custodial sentences or guilty verdicts. It was especially high with recent or frequent contact and in people charged with violent offenses. We examined a section of society in which major health and social problems frequently coexist including offending, psychopathology, and suicidal behavior. The need for developing more far-reaching national suicide prevention strategies is indicated. In particular, improved mental health service provision is needed for all people in contact with the criminal justice system, including those not found guilty and those not given custodial sentences. Our findings also suggest that public services should be better coordinated to tackle co-occurring health and social problems more effectively.

Long-Term Survival and Quality of Life After Transfusion-Associated Pulmonary Edema in Critically III Medical Patients

PubMed Central

Kojicic, Marija; Reriani, Martin K.; Fernández Pérez, Evans R.; Thakur, Lokendra; Kashyap, Rahul; Van Buskirk, Camille M.; Gajic, Ognjen

2010-01-01

Background: Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) commonly complicate transfusion in critically ill patients. Prior outcome studies of TACO and TRALI have focused on short-term morbidity and mortality, but the long-term survival and quality of life (QOL) of these patients remain unknown. Methods: In a nested case-control study, we compared survival and QOL between critically ill medical patients who developed pulmonary edema after transfusion (TRALI or TACO) and medical critically ill transfused controls, matched by age, gender, and admission diagnostic group. QOL in survivors was assessed with a 36-item short form health survey 1 year after initial hospitalization. Results: Hospital, 1-year, and 2-year mortality among the 74 TRALI cases and 74 matched controls were 43.2% vs 24.3% (P = .020), 63.8% vs 46.4% (P = .037) and 74.3% vs 54.3% (P = .031), whereas among the 51 TACO cases and 51 matched controls these values were 7.8% vs 11.8% (P = .727), 38.0% vs 28.0% (P = .371), and 44.9% vs 38.8% (P = .512). When adjusted for age and baseline severity of illness in a Cox proportional hazard analysis, the development of TRALI remained associated with decreased survival (hazard ratio 1.86; 95% CI, 1.19-2.93; P = .006). Both TRALI (P = .006, P = .03) and TACO (P = .03, P = .049) were associated with prolonged ICU and hospital lengths of stay. Conclusions: In critically ill medical patients, development of TRALI, but not TACO, is independently associated with decreased long-term survival. PMID:19837827

Radiation dose and subsequent risk for stomach cancer in long-term survivors of cervical cancer

PubMed Central

Kleinerman, Ruth A.; Smith, Susan A.; Holowaty, Eric; Hall, Per; Pukkala, Eero; Vaalavirta, Leila; Stovall, Marilyn; Weathers, Rita; Gilbert, Ethel; Aleman, Berthe M.P.; Kaijser, Magnus; Andersson, Michael; Storm, Hans; Joensuu, Heikki; Lynch, Charles F.; Dores, Graça M.; Travis, Lois B.; Morton, Lindsay M.; Curtis, Rochelle E.

2013-01-01

Purpose To assess the dose-response relationship for stomach cancer following radiotherapy for cervical cancer. Methods and Materials We conducted a nested, matched case-control study of 201 cases and 378 controls among 53,547 5-year survivors of cervical cancer diagnosed from 1943–1995, from five international, population-based cancer registries. We estimated individual radiation doses to the site of the stomach cancer for all cases and to corresponding sites for the matched controls (overall mean stomach tumor dose, 2.56 gray [Gy], range 0.03–46.1 and following parallel opposed pelvic fields, 1.63 Gy, range 0.12–6.3). Results Over 90% of women received radiotherapy, mostly with external beam therapy in combination with brachytherapy. Stomach cancer risk was non-significantly increased (odds ratios [ORs] 1.27–2.28) for women receiving between 0.5–4.9 Gy to the stomach cancer site and significantly increased at doses ≥5 Gy (OR=4.20, 95% confidence interval, 1.41–13.4, Ptrend=0.047) compared to non-irradiated women. A highly significant radiation dose-response relationship was evident when analyses were restricted to the 131 cases (251 controls) whose stomach cancer was located in the middle and lower portions of the stomach (Ptrend=0.003), whereas there was no indication of increasing risk with increasing dose for 30 cases (57 controls) whose cancer was located in the upper stomach (Ptrend=0.23). Conclusions Our findings showed for the first time a significant linear dose-response relationship for risk of stomach cancer in long-term survivors of cervical cancer. PMID:23707149

There Is No Difference in IQ between Suicide and Non-Suicide Psychiatric Patients: A Retrospective Case-Control Study.

PubMed

Park, Sung-Jin; Yi, Kikyoung; Lee, Joon Deuk; Hong, Jin Pyo

2015-07-01

The goal of this study was to examine the association between IQ and suicide in psychiatric patients. We conducted a nested case-control study using data obtained from psychiatric patients affiliated with a general hospital in Seoul, Korea. In a one-to-two ratio the psychiatric patients who died of suicide (Suicide Group; n=35) were matched to those who didn't (Non-suicide Group; n=70) by age, gender, psychiatric diagnosis and approximate time of first treatment. IQ was measured using the Korean version of the Wechsler Adult Intelligence Scale-Revised. There were no significant differences in any type of IQ between suicide patients and non-suicide patients. Logistic regression showed no evidence of an association between IQ and suicide. These results do not support the existence of an association between IQ and suicide.

Specific and Non-specific Clinical Presentations in the Year Before the Diagnosis of Childhood Leukaemia.

PubMed

Yang, TienYu Owen; Liu, Yen-Lin; Huang, Wan-Ting; Chen, Mei-Huei; Chen, Pau-Chung

2016-08-01

Clinical presentations of childhood leukaemia have been reported in case-only studies. The timing when these presentations start to occur prior to diagnosis is less clear. In this nested case-control study, 1,025 and 334 children with lymphoid and myeloid leukaemia, respectively, were matched (1:30) to population-based controls by sex, region and year of birth. An index date was assigned for each control when the matched case was diagnosed. Healthcare access records of cases and controls in the year before the index date were extracted. Children with lymphoid leukaemia started to visit doctors more often at least 2 months before leukaemia diagnosis (P < 0.05). Various presentations were recorded in these visits: rates of haematological presentations, musculoskeletal presentations, and injuries started to increase significantly at least 3 months before diagnosis; rates of respiratory, gastrointestinal and urinary tract presentations did not increase significantly until the last month. The findings for myeloid lymphoma were less clear, but children appeared to visit doctors more often at least 4 months before diagnosis, and the rate of haematological presentations also started to increase at least 4 months before leukaemia diagnosis. Although haematological presentations were most strongly associated with undiagnosed leukaemia (odds ratio > 290 in the last month), the majority (>96%) of children with haematological presentations did not have leukaemia if they had not been diagnosed in their first visit. We described a clinical picture in the year before leukaemia diagnosis. These findings revealed ongoing difficulties in early diagnosis of childhood leukaemia in healthcare settings. © 2016 Wiley Periodicals, Inc.

Tachycardia may prognosticate life- or organ-threatening diseases in children with abdominal pain.

PubMed

Hayakawa, Itaru; Sakakibara, Hiroshi; Atsumi, Yukari; Hataya, Hiroshi; Terakawa, Toshiro

2017-06-01

Abdominal pain is common in children, but expeditious diagnosis of life- or organ-threatening diseases can be challenging. An evidence-based definition of tachycardia in children was established recently, but its diagnostic utility has not yet been studied. To test the hypothesis that abdominal pain with tachycardia may pose a higher likelihood of life- or organ-threatening diseases in children. A nested case-control study was conducted in a pediatric emergency department in 2013. Tachycardia was defined as a resting heart rate of more than 3 standard deviations above the average for that age. Life- or organ-threatening diseases were defined as "disorders that might result in permanent morbidity or mortality without appropriate intervention." A triage team recorded vital signs before emergency physicians attended patients. Patients with tachycardia (cases) and without tachycardia (controls) were systematically matched for age, sex, and month of visit. The groups were compared for the presence of life- or organ-threatening diseases. There were 1683 visits for abdominal pain, 1512 of which had vital signs measured at rest. Eighty-three patients experienced tachycardia, while 1429 did not. Fifty-eight cases and 58 controls were matched. Life- or organ-threatening diseases were more common in the case group (19%) than the control group (5%, p=0.043). The relative risk of tachycardia to the presence of the diseases was 3.7 (95% confidence interval 1.2-12.0). Tachycardia significantly increased the likelihood of life- or organ-threatening diseases. Tachycardia in children with abdominal pain should alert emergency physicians to the possibility of serious illness. Copyright © 2017 Elsevier Inc. All rights reserved.

The Influence of Health and Lifestyle Characteristics on the Relation of Serum 25-Hydroxyvitamin D With Risk of Colorectal and Breast Cancer in Postmenopausal Women

PubMed Central

Neuhouser, Marian L.; Manson, JoAnn E.; Millen, Amy; Pettinger, Mary; Margolis, Karen; Jacobs, Elizabeth T.; Shikany, James M.; Vitolins, Mara; Adams-Campbell, Lucile; Liu, Simin; LeBlanc, Erin; Johnson, Karen C.; Wactawski-Wende, Jean

2012-01-01

The authors’ objective was to discern whether lifestyle or health-related factors were confounders, effect modifiers, or irrelevant with regard to understanding observational associations of serum 25-hydroxyvitamin D (25(OH)D) with colorectal and breast cancer. The authors conducted nested case-control studies of colorectal cancer (310 cases, 310 controls) and breast cancer (1,080 cases, 1,080 controls) in the Women’s Health Initiative Calcium and Vitamin D Clinical Trial (1994–2005). Case-control matching factors included age, latitude, race/ethnicity, and blood collection date. Serum 25(OH)D was assayed in baseline fasting blood. Conditional logistic regression was used to estimate odds ratios for each cancer by serum 25(OH)D concentration, comparing the relative effects of successively adding body mass index, physical activity, and other health and lifestyle characteristics particular to each cancer. In models with matching factors only, low (vs. high) serum 25(OH)D was associated with a colorectal cancer odds ratio of 2.72 (95% confidence interval (CI): 1.55, 4.77) and a breast cancer odds ratio of 1.33 (95% CI: 1.02, 1.72). In multivariate-adjusted models for colorectal cancer, the association strengthened (OR = 4.45, 95% CI: 1.96, 10.10). However, in multivariate-adjusted breast cancer models, associations were no longer significant (OR = 1.06, 95% CI: 0.78, 1.43). Adjusting for health and lifestyle characteristics has differential effects depending on the cancer site; when modeling such relations, investigators should take these factors into account. PMID:22362582

Acute Myocardial Infarction Risk in Patients with Coronary Artery Disease Doubled after Upper Gastrointestinal Tract Bleeding: A Nationwide Nested Case-Control Study

PubMed Central

Weng, Shih-Feng; Hsu, Chien-Chin; Wang, Jhi-Joung; Su, Shih-Bin; Huang, Chien-Cheng; Guo, How-Ran

2015-01-01

Prior studies of upper gastrointestinal bleeding (UGIB) and acute myocardial infarction (AMI) are small, and long-term effects of UGIB on AMI have not been delineated. We investigated whether UGIB in patients diagnosed with coronary artery disease (CAD) increased their risk of subsequent AMI. This was a population-based, nested case-control study using Taiwan’s National Health Insurance Research Database. After propensity-score matching for age, gender, comorbidities, CAD date, and follow-up duration, we identified 1,677 new-onset CAD patients with AMI (AMI[+]) between 2001 and 2006 as the case group and 10,062 new-onset CAD patients without (AMI[−]) as the control group. Conditional logistic regression was used to examine the association between UGIB and AMI. Compared with UGIB[−] patients, UGIB[+] patients had twice the risk for subsequent AMI (adjusted odds ratio [AOR] = 2.08; 95% confidence interval [CI], 1.72–2.50). In the subgroup analysis for gender and age, UGIB[+] women (AOR = 2.70; 95% CI, 2.03–3.57) and patients < 65 years old (AOR = 2.23; 95% CI, 1.56–3.18) had higher odds of an AMI. UGIB[+] AMI[+] patients used nonsignificantly less aspirin than did UGIB[−] AMI[+] patients (27.69% vs. 35.61%, respectively). UGIB increased the risk of subsequent AMI in CAD patients, especially in women and patients < 65. This suggests that physicians need to use earlier and more aggressive intervention to detect UGIB and prevent AMI in CAD patients. PMID:26529110

Prior human polyomavirus and papillomavirus infection and incident lung cancer: a nested case-control study.

PubMed

Colombara, Danny V; Manhart, Lisa E; Carter, Joseph J; Hawes, Stephen E; Weiss, Noel S; Hughes, James P; Barnett, Matt J; Goodman, Gary E; Smith, Jennifer S; Qiao, You-Lin; Galloway, Denise A

2015-12-01

To test whether infection with select human polyomaviruses (HPyV) and human papillomaviruses (HPV) is associated with incident lung cancer. We performed a nested case-control study, testing serum from the carotene and retinol efficacy trial, conducted 1985-2005, for antibodies to Merkel cell (MCV), KI (KIV), and WU (WUV) HPyVs as well as to six high-risk and two low-risk HPV types. Incident lung cancer cases (n = 200) were frequency-matched with controls (n = 200) on age, enrollment and blood draw dates, intervention arm assignment, and the number of serum freeze/thaw cycles. Sera were tested using multiplex liquid bead microarray antibody assays. We used logistic regression to assess the association between HPyV and HPV antibodies and lung cancer. There was no evidence of a positive association between levels of MCV, KIV, or WUV antibodies and incident lung cancer (p corrected >0.10 for all trend tests; odds ratio (OR) range 0.72-1.09, p corrected >0.10 for all). There was also no evidence for a positive association between HPV 16 or 18 infection and incident lung cancer (p corrected ≥0.10 for all trend tests; OR range 0.25-2.54, p > 0.05 for all OR > 1), but the number of persons with serologic evidence of these infections was small. Prior infection with any of several types of HPyV or HPV was not associated with subsequent diagnosis of lung cancer. Infection with these viruses likely does not influence a person's risk of lung cancer in Western smoking populations.

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.

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

PubMed

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

2014-08-08

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

Diet and alcohol as risk factors for rheumatoid arthritis: a nested case-control study.

PubMed

Sundström, B; Johansson, I; Rantapää-Dahlqvist, S

2015-03-01

The aim of this study was to investigate whether alcohol and diet, assessed as both macronutrients and dietary patterns, increased the risk of development of rheumatoid arthritis (RA) through a nested case-control design in the Västerbotten Intervention Program (VIP) cohort. Individuals in the VIP who had developed RA after the dietary survey were identified from medical records at the department of rheumatology at the University Hospital, Umeå (n = 386), and matched to 1,886 controls from the same database. Diet was assessed as food groups, as macronutrients and as scores of dietary patterns, namely the carbohydrate-restricted diet score, the Mediterranean diet score and the healthy diet indicator score. When analysing the dietary patterns, consumption of food groups and different macronutrients, a significant association was found in the highest tertile of carbohydrate-restricted diet among the cases with a subsequent anti-CCP-positive disease 1.40 (1.02-1.92), as well as in the highest tertile of protein consumption among smokers (OR = 1.80, 95% CI 1.09-2.95). However, after additional adjustment for sodium intake, these associations were no longer statistically significant. No association was observed between alcohol consumption and the risk of RA. To summarize, there were no significant associations between diet, or alcohol consumption, and the risk of development of RA within this cohort. The lack of any significant associations of alcohol consumption may be explained by a low consumption in the studied population overall or alternatively by methodological issues raised recently.

Prenatal exposure to glycol ethers and cryptorchidism and hypospadias: a nested case-control study.

PubMed

Warembourg, Charline; Botton, Jérémie; Lelong, Nathalie; Rouget, Florence; Khoshnood, Babak; Le Gléau, Florent; Monfort, Christine; Labat, Laurence; Pierre, Fabrice; Heude, Barbara; Slama, Rémy; Multigner, Luc; Charles, Marie-Aline; Cordier, Sylvaine; Garlantézec, Ronan

2018-01-01

Glycol ethers (GE) are oxygenated solvents frequently found in occupational and consumer products. Some of them are well-known testicular and developmental animal toxicants. This study aims to evaluate the risk of male genital anomalies in association with prenatal exposure to GE using urinary biomarkers of exposure. We conducted a case-control study nested in two joint mother-child cohorts (5303 pregnant women). Cases of cryptorchidism and hypospadias were identified at birth and confirmed during a 2-year follow-up period (n=14 cryptorchidism and n=15 hypospadias). Each case was matched to three randomly selected controls within the cohorts for region of inclusion and gestational age at urine sampling. Concentrations of five GE acidic metabolites were measured in spot maternal urine samples collected during pregnancy. ORs were estimated with multivariate conditional logistic regressions including a Firth's penalisation. Detection rates of urinary GE metabolites ranged from 8% to 93% and only two were sufficiently detected (>33%) in each cohort to be studied: methoxyacetic acid (MAA) and phenoxyacetic acid (PhAA). A significantly higher risk of hypospadias was associated with the highest tertile of exposure to MAA: OR (95% CI) 4.5(1.4 to 23.4). No association were observed with urinary concentration of PhAA, nor with the risk of cryptorchidism. In view of the toxicological plausibility of our results, this study, despite its small sample size, raises concern about the potential developmental toxicity of MAA on the male genital system and calls for thorough identification of current sources of exposure to MAA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Vitamin D–binding protein and pancreatic cancer: a nested case-control study12345

PubMed Central

Piper, Marina R; Freedman, D Michal; Robien, Kim; Kopp, William; Rager, Helen; Horst, Ronald L

2015-01-01

Background: Vitamin D–binding protein (DBP) is the primary carrier of 25-hydroxyvitamin D [25(OH)D] in the circulation. One prospective study in male smokers found a protective association between DBP and pancreatic cancer, particularly among men with higher 25(OH)D concentrations. Objective: The objective was to examine the association between DBP and pancreatic cancer risk in an American population. Design: We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer screening trial cohort of men and women aged 55–74 y at baseline. Between 1993 and 2010, 295 incident pancreatic adenocarcinoma cases were reported (follow-up to 15.1 y). Two controls (n = 590) were matched to each case by age, race, sex, and month of blood draw. We calculated smoking- and diabetes-adjusted ORs and 95% CIs with the use of conditional logistic regression. Results: DBP concentration was not significantly associated with pancreatic cancer overall [highest (≥7149.4 nmol/L) vs. lowest (<3670.4 nmol/L) quintile; OR: 1.75; 95% CI: 0.91, 3.37; P-trend = 0.25]. For serum 25(OH)D compared with the referent (50 to <75 nmol/L), individuals in the highest group had a significantly higher risk (≥100 nmol/L; OR: 3.23; 95% CI: 1.24, 8.44), whereas those in the lowest group had no significant association (<25 nmol/L; OR: 2.50; 95% CI: 0.92, 6.81). Further adjustment for DBP did not alter this association. Conclusion: Our results do not support the hypothesis that serum DBP or 25(OH)D plays a protective role in pancreatic cancer. This trial was registered at clinicaltrials.gov as NCT00339495. PMID:25904602

The effects of aminosalicylates or thiopurines on the risk of colorectal cancer in inflammatory bowel disease.

PubMed

Carrat, F; Seksik, P; Colombel, J-F; Peyrin-Biroulet, L; Beaugerie, L

2017-02-01

Whether aminosalicylates or thiopurines reduce the risk of colorectal cancer (CRC) in inflammatory bowel (IBD) disease is controversial. To assess simultaneously the chemopreventive effect of aminosalicylates or thiopurines in a case-control study nested in the CESAME observational cohort that enrolled consecutive patients with IBD between May 2004 and June 2005. Patients were followed up to December 2007. Study population comprised 144 case patients who developed CRC from the diagnosis of IBD (65 and 79 cases diagnosed, respectively, before and from 2004, starting year of the prospective observational period of CESAME) and 286 controls matched for gender, age, IBD subtype and year of diagnosis, and cumulative extent of colitis. Exposure to aminosalicylates or thiopurines was defined by an exposure to the treatment during the year of the diagnosis of cancer. The propensity of receiving 5-ASA and thiopurines was quantified by a composite score taking into account patient and IBD characteristics. The role of aminosalicylates or thiopurines was assessed by multivariate analysis. Propensity scores and the history of primary sclerosing cholangitis were entered into the multivariate model for adjustment. By multivariate analysis adjusted for propensity, a significant protective effect of exposure to drugs during the year of cancer was found for aminosalicylates (OR = 0.587, 95% CI: 0.367-0.937, P = 0.0257), but not for thiopurines (OR = 0.762, 95% CI: 0.432-1.343, P = 0.3468). In a case-control study nested in the CESAME cohort, a significant decrease in the risk of colorectal cancer in IBD was associated with exposure to aminosalicylates, not to thiopurines. © 2016 John Wiley & Sons Ltd.

The effect of pre-pregnancy hair dye exposure on infant birth weight: a nested case-control study.

PubMed

Jiang, Chao; Hou, Qingzhi; Huang, Yaling; Ye, Juan; Qin, Xiaolian; Zhang, Yu; Meng, Wen; Wang, Qiuyan; Jiang, Yonghua; Zhang, Haiying; Li, Mujun; Mo, Zengnan; Yang, Xiaobo

2018-05-09

Limited evidences were reported about the risk of pre-pregnancy hair dye use or irregular menstruation with abnormal birth weight during pregnancy, and their joint effects were also unknown. The aim of our study was to explore whether the pre-pregnancy exposure of hair dye and irregular menstruation were associated with the risk of abnormal birth weight. We conducted a nested case-control study from a prospective cohort of 6203 pregnant women. Low birth weight study included 315 mother-infant pairs (105 LBW cases and 210 matched controls), and macrosomia study included 381 mother-infant pairs (127 macrosomia cases and 254 matched controls). Meanwhile, lifestyle information including hair dying custom and menstrual history were collected by face-to-face questionnaires and birth outcomes were extracted from the medical records. The logistic regressions models were used to analyze the join effect of irregular menstruation and hair dye use. Pre-pregnancy hair dye use was associated with increased risk of LBW (adjusted OR = 1.71, 95% CI: 1.01-2.92, P = 0.048). Irregular menstruation had high risk of LBW (adjusted OR = 2.79, 95% CI: 1.53-5.09, P = 0.001) and macrosomia (adjusted OR = 1.93, 95% CI: 1.09-3.44, P = 0.023). Additionally, in the LBW study, women who used hair dye with pre-pregnancy BMI < 18.5 kg/m 2 had higher OR than those with only one risk factor (3.07 vs 2.53, P trend  = 0.015), and women with both hair dye use and irregular menstruation also had higher risk than those with only one factor (4.53 vs 2.07, P trend  = 0.05). Moreover, in macrosomia study, women with irregular menstruation and pre-pregnancy BMI ≥ 24 kg/m 2 had higher risk than those with one factor (13.31 vs 2.09, P trend  = 0.001). Our study showed that either pre-pregnancy hair dye use or irregular menstruation was associated with abnormal birth weight, especially, their joint effects could furthermore increase the risk of low birth weight infants when these two factors existed simultaneously.

Incremental cost effectiveness of proton pump inhibitors for the prevention of non-steroidal anti-inflammatory drug ulcers: a pharmacoeconomic analysis linked to a case-control study.

PubMed

Vonkeman, Harald E; Braakman-Jansen, Louise M A; Klok, Rogier M; Postma, Maarten J; Brouwers, Jacobus R B J; van de Laar, Mart A F J

2008-01-01

We estimated the cost effectiveness of concomitant proton pump inhibitors (PPIs) in relation to the occurrence of non-steroidal anti-inflammatory drug (NSAID) ulcer complications. This study was linked to a nested case-control study. Patients with NSAID ulcer complications were compared with matched controls. Only direct medical costs were reported. For the calculation of the incremental cost effectiveness ratio we extrapolated the data to 1,000 patients using concomitant PPIs and 1,000 patients not using PPIs for 1 year. Sensitivity analysis was performed by 'worst case' and 'best case' scenarios in which the 95% confidence interval (CI) of the odds ratio (OR) and the 95% CI of the cost estimate of a NSAID ulcer complication were varied. Costs of PPIs was varied separately. In all, 104 incident cases and 284 matched controls were identified from a cohort of 51,903 NSAID users with 10,402 NSAID exposition years. Use of PPIs was associated with an adjusted OR of 0.33 (95% CI 0.17 to 0.67; p = 0.002) for NSAID ulcer complications. In the extrapolation the estimated number of NSAID ulcer complications was 13.8 for non-PPI users and 3.6 for PPI users. The incremental total costs were euro 50,094 higher for concomitant PPIs use. The incremental cost effectiveness ratio was euro 4,907 per NSAID ulcer complication prevented when using the least costly PPIs. Concomitant use of PPIs for the prevention of NSAID ulcer complications costs euro 4,907 per NSAID ulcer complication prevented when using the least costly PPIs. The price of PPIs highly influenced the robustness of the results.

The Leganés cognitive test correlates poorly with MRI evidence of global cortical atrophy in an underserved community: A population-based and nested case-control study in rural Ecuador (The Atahualpa Project)

PubMed Central

Brutto, Oscar H. Del; Mera, Robertino M; Zambrano, Mauricio; Lama, Julio

2014-01-01

Objective We aimed to evaluate whether the Leganés cognitive test (LCT) correlates with global cortical atrophy (GCA) and can be used as a surrogate for structural brain damage. Methods Atahualpa residents aged > 60 years identified during a door-to-door survey underwent MRI for grading GCA. Using multivariate generalized linear models, we evaluated whether continuous LCT scores correlated with GCA, after adjusting for demographics, education, cardiovascular health (CVH) status, depression and edentulism. In a nested case-control study, GCA severity was assessed in subjects with LCT scores below the cutoff level for dementia (< 22 points) and in matched controls without dementia. Results Out of 311 eligible subjects, 241 (78%) were enrolled. Mean age was 69.2±7.5 years, 59% were women, 83% had primary school education, 73% had poor CVH status, 12% had symptoms of depression and 43% had edentulism. Average LCT score was 26.7±3, and 23 (9.5%) subjects scored < 22 points. GCA was mild in 108, moderate in 95, and severe in 26 individuals. On the multivariate model, mean LCT score was not associated with GCA severity (β=0.06, SE=0.34, p=0.853). Severe GCA was noted in 6 / 23 case-patients and in 8 / 23 controls (OR: 0.67, 95% CI: 0.14-2.81, p=0.752, McNemar's test). Conclusion The LCT does not correlate with severity of GCA after adjusting for potential confounding variables, and should not be used as a reliable estimate of structural brain damage. PMID:29213925

The Leganés cognitive test correlates poorly with MRI evidence of global cortical atrophy in an underserved community: A population-based and nested case-control study in rural Ecuador (The Atahualpa Project).

PubMed

Brutto, Oscar H Del; Mera, Robertino M; Zambrano, Mauricio; Lama, Julio

2014-01-01

We aimed to evaluate whether the Leganés cognitive test (LCT) correlates with global cortical atrophy (GCA) and can be used as a surrogate for structural brain damage. Atahualpa residents aged > 60 years identified during a door-to-door survey underwent MRI for grading GCA. Using multivariate generalized linear models, we evaluated whether continuous LCT scores correlated with GCA, after adjusting for demographics, education, cardiovascular health (CVH) status, depression and edentulism. In a nested case-control study, GCA severity was assessed in subjects with LCT scores below the cutoff level for dementia (< 22 points) and in matched controls without dementia. Out of 311 eligible subjects, 241 (78%) were enrolled. Mean age was 69.2±7.5 years, 59% were women, 83% had primary school education, 73% had poor CVH status, 12% had symptoms of depression and 43% had edentulism. Average LCT score was 26.7±3, and 23 (9.5%) subjects scored < 22 points. GCA was mild in 108, moderate in 95, and severe in 26 individuals. On the multivariate model, mean LCT score was not associated with GCA severity (β=0.06, SE=0.34, p=0.853). Severe GCA was noted in 6 / 23 case-patients and in 8 / 23 controls (OR: 0.67, 95% CI: 0.14-2.81, p=0.752, McNemar's test). The LCT does not correlate with severity of GCA after adjusting for potential confounding variables, and should not be used as a reliable estimate of structural brain damage.

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.

Major histocompatibility complex (MHC) class I and II alleles which confer susceptibility or protection in the Morphea in Adults and Children (MAC) cohort

PubMed Central

Jacobe, Heidi; Ahn, Chul; Arnett, Frank; Reveille, John D.

2014-01-01

Objective To determine human leukocyte antigen class I (HLA-class I) and II (HLA-class II) alleles associated with morphea (localized scleroderma) in the Morphea in Adults and Children (MAC) cohort by a nested case–control association study. Methods Morphea patients were included from MAC cohort and matched controls from the NIH/NIAMS Scleroderma Family Registry and DNA Repository and Division of Rheumatology at the University of Texas Health Science Center at Houston. HLA- Class II genotyping and SSCP typing was performed of HLA-A, -B, -C alleles. Associations between HLA-Class I and II alleles and morphea as well as its subphenotypes were determined. Results There were 211 cases available for HLA-class I typing with 726 matched controls and 158 cases available for HLA Class-II typing with 1108 matched controls. The strongest associations were found with DRB1*04:04 (OR 2.3, 95% CI 1.4–4.0 P=0.002) and HLA-B*37 conferred the highest OR among Class I alleles (3.3, 95% CI 1.6–6.9, P= 0.0016). Comparison with risk alleles in systemic sclerosis determined using the same methods and control population revealed one common allele (DRB*04:04). Conclusion Results of the present study demonstrate specific HLA Class I and II alleles are associated with morphea and likely generalized and linear subtypes. The associated morphea alleles are different than in scleroderma, implicating morphea is also immunogenetically distinct. Risk alleles in morphea are also associated with conditions such as rheumatoid arthritis (RA) and other autoimmune conditions. Population based studies indicate patients with RA have increased risk of morphea, implicating a common susceptibility allele. PMID:25223600

Hospitalisation for chronic obstructive pulmonary disease and risk of suicide: a population-based case–control study

PubMed Central

Strid, Jennie Maria Christin; Christiansen, Christian Fynbo; Olsen, Morten; Qin, Ping

2014-01-01

Objectives To examine risk of suicide among individuals with hospitalised chronic obstructive pulmonary disease (COPD) and to profile differences according to sex, age, psychiatric history, and recency and frequency of COPD hospitalisations. Design Nested case–control study. Setting Data were retrieved from Danish national registries. Participants All suicide cases aged 40–95 years deceased between 1981 and 2006 in Denmark (n=19 869) and up to 20 live population controls per case matched on sex and date of birth (n=321 867 controls). Main outcome measures The relative risk of suicide associated with COPD was computed using conditional logistic regression and adjusted for effects of psychiatric history and important sociodemographic factors. Results In our study population, 3% of suicide cases had been hospitalised for COPD compared with 1% of matched population controls. Thus, a hospitalised COPD was associated with a significantly increased risk for suicide (OR 2.6; 95% CI 2.3 to 2.8). The increased risk remained significant after adjustment for psychiatric history and sociodemographic variables (OR 2.0; 95% CI 1.8 to 2.2), and increased progressively with frequency and recency of COPD hospitalisation. At the same time, suicide risk associated with COPD differed significantly by sex, age and psychiatric status. The relative risk was more pronounced in women, in individuals older than 60 years and in persons with no history of psychiatric illness. Conclusions COPD confers an important risk factor for suicide completion. Risk assessment and prevention efforts should take patients’ sex, age and psychiatric history into consideration. PMID:25421339

Use of Hypoprothrombinemia-Inducing Cephalosporins and the Risk of Hemorrhagic Events: A Nationwide Nested Case-Control Study

PubMed Central

Shen, Li-Jiuan; Wu, Fe-Lin Lin; Tsay, Woei; Hung, Chien-Ching; Lin, Shu-Wen

2016-01-01

Objective Existing data regarding the risk of hemorrhagic events associated with exposure to hypoprothrombinemia-inducing cephalosporins are limited by the small sample size. This population-based study aimed to examine the association between exposure to hypoprothrombinemia-inducing cephalosporins and hemorrhagic events using National Health Insurance Research Database in Taiwan. Design A nationwide nested case-control study. Setting National Health Insurance Research database. Participants We conducted a nested case-control study within a cohort of 6191 patients who received hypoprothrombinemia-inducing cephalosporins and other antibiotics for more than 48 hours. Multivariable conditional logistic regressions were used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for hemorrhagic events associated with exposure to hypoprothrombinemia-inducing cephalosporins (overall, cumulative dose measured as defined daily dose (DDD), and individual cephalosporins). Results Within the cohort, we identified 704 patients with hemorrhagic events and 2816 matched controls. Use of hypoprothrombinemia-inducing cephalosporins was associated with increased risk of hemorrhagic events (aOR, 1.71; 95% CI, 1.42–2.06), which increased with higher cumulative doses (<3 DDDs, aOR 1.62; 3–5 DDDs, aOR 1.78; and >5 DDDs, aOR 1.89). The aOR for individual cephalosporin was 2.88 (95% CI, 2.08–4.00), 1.35 (1.09–1.67) and 4.57 (2.63–7.95) for cefmetazole, flomoxef, and cefoperazone, respectively. Other risk factors included use of anticoagulants (aOR 2.08 [95% CI, 1.64–2.63]), liver failure (aOR 1.69 [1.30–2.18]), poor nutritional status (aOR 1.41 [1.15–1.73]), and history of hemorrhagic events (aOR 2.57 [1.94–3.41]) 6 months prior to the index date. Conclusions Use of hypoprothrombinemia-inducing cephalosporins increases risk of hemorrhagic events. Close watch for hemorrhagic events is recommended when prescribing these cephalosporins, especially in patients who are at higher risk. PMID:27463687

Radiation Dose and Subsequent Risk for Stomach Cancer in Long-term Survivors of Cervical Cancer

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

Kleinerman, Ruth A., E-mail: kleinerr@mail.nih.gov; Smith, Susan A.; Holowaty, Eric

2013-08-01

Purpose: To assess the dose–response relationship for stomach cancer after radiation therapy for cervical cancer. Methods and Materials: We conducted a nested, matched case–control study of 201 cases and 378 controls among 53,547 5-year survivors of cervical cancer diagnosed from 1943 to 1995, from 5 international, population-based cancer registries. We estimated individual radiation doses to the site of the stomach cancer for all cases and to corresponding sites for the matched controls (overall mean stomach tumor dose, 2.56 Gy, range 0.03-46.1 and after parallel opposed pelvic fields, 1.63 Gy, range 0.12-6.3). Results: More than 90% of women received radiation therapy,more » mostly with external beam therapy in combination with brachytherapy. Stomach cancer risk was nonsignificantly increased (odds ratio 1.27-2.28) for women receiving between 0.5 and 4.9 Gy to the stomach cancer site and significantly increased at doses ≥5 Gy (odds ratio 4.20, 95% confidence interval 1.41-13.4, P{sub trend}=.047) compared with nonirradiated women. A highly significant radiation dose–response relationship was evident when analyses were restricted to the 131 cases (251 controls) whose stomach cancer was located in the middle and lower portions of the stomach (P{sub trend}=.003), whereas there was no indication of increasing risk with increasing dose for 30 cases (57 controls) whose cancer was located in the upper stomach (P{sub trend}=.23). Conclusions: Our findings show for the first time a significant linear dose–response relationship for risk of stomach cancer in long-term survivors of cervical cancer.« less

Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study.

PubMed

Fedirko, Veronika; Tran, Hao Quang; Gewirtz, Andrew T; Stepien, Magdalena; Trichopoulou, Antonia; Aleksandrova, Krasimira; Olsen, Anja; Tjønneland, Anne; Overvad, Kim; Carbonnel, Franck; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Kühn, Tilman; Kaaks, Rudolf; Boeing, Heiner; Bamia, Christina; Lagiou, Pagona; Grioni, Sara; Panico, Salvatore; Palli, Domenico; Tumino, Rosario; Naccarati, Alessio; Peeters, Petra H; Bueno-de-Mesquita, H B; Weiderpass, Elisabete; Castaño, José María Huerta; Barricarte, Aurelio; Sánchez, María-José; Dorronsoro, Miren; Quirós, J Ramón; Agudo, Antonio; Sjöberg, Klas; Ohlsson, Bodil; Hemmingsson, Oskar; Werner, Mårten; Bradbury, Kathryn E; Khaw, Kay-Tee; Wareham, Nick; Tsilidis, Konstantinos K; Aune, Dagfinn; Scalbert, Augustin; Romieu, Isabelle; Riboli, Elio; Jenab, Mazda

2017-04-04

Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking. We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression. Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70-81.40; P trend  = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses. These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.

NO2, as a marker of air pollution, and recurrent wheezing in children: a nested case-control study within the BAMSE birth cohort.

PubMed

Emenius, G; Pershagen, G; Berglind, N; Kwon, H-J; Lewné, M; Nordvall, S L; Wickman, M

2003-11-01

To investigate the association between air pollution, including with NO2, and recurrent wheezing during the first two years of life. A birth cohort (BAMSE) comprised 4089 children, for whom information on exposures, symptoms, and diseases was available from parental questionnaires at ages 2 months, and 1 and 2 years. NO2 was measured during four weeks in and outside the dwellings of children with recurrent wheezing and two age matched controls, in a nested case-control study (540 children). Conditional logistic regression showed an OR of 1.60 (95% CI 0.78 to 3.26) among children in the highest quartile of outdoor NO2 exposure in relation to those in the lowest quartile, adjusted for potential confounders. The corresponding OR for indoor NO2 was 1.51 (95% CI 0.81 to 2.82). An interaction with environmental tobacco smoke (ETS) was indicated with an OR of 3.10 (95% CI 1.32 to 7.30) among children exposed to the highest quartile of indoor NO2 and ETS. The association between NO2 and recurrent wheezing appeared stronger in children who did not fulfil the criteria for recurrent wheezing until their second year. Although the odds of increased recurrent wheezing are not statistically significantly different from one, results suggest that exposure to air pollution including NO2, particularly in combination with exposure to ETS, increases the risk of recurrent wheezing in children.

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

The value of reasons for encounter in early detection of colorectal cancer.

PubMed

van Boxtel-Wilms, Susan J M; van Boven, Kees; Bor, J H Hans; Bakx, J Carel; Lucassen, Peter; Oskam, Sibo; van Weel, Chris

2016-06-01

Symptoms with a high predictive power for colorectal cancer (CRC) do not exist. To explore the predictive value of patients' reason for encounter (RFE) in the two years prior to the diagnosis of CRC. A retrospective nested case-control study using prospectively collected data from electronic records in general practice over 20 years. Matching was done based on age (within two years), gender and practice. The positive likelihood ratios (LR+) and odds ratios (OR) were calculated for RFE between cases and controls in the two years before the index date. We identified 184 CRC cases and matched 366 controls. Six RFEs had significant LR + and ORs for CRC, which may have high predictive power. These RFEs are part of four chapters in the International Classification of Primary Care (ICPC) that include tiredness (significant at 3-6 months prior to the diagnosis; LR+ 2.6 and OR 3.07; and from 0 to 3 months prior to the diagnosis; LR+ 2.0 and OR 2.36), anaemia (significant at three months before diagnosis; LR+ 9.8 and OR 16.54), abdominal pain, rectal bleeding and constipation (significant at 3-6 months before diagnosis; LR+ 3.0 and OR 3.33; 3 months prior to the diagnosis LR+ 8.0 and OR 18.10) and weight loss (significant at three months before diagnosis; LR+ 14.9 and OR 14.53). Data capture and organization in ICPC permits study of the predictive value of RFE for CRC in primary care.

A Prospective Study Investigating Pre-diagnostic Leukocyte Telomere Length and Risk of Developing Rheumatoid Arthritis in Women

PubMed Central

Prescott, Jennifer; Karlson, Elizabeth W.; Orr, Esther H.; Zee, Robert Y.L.; De Vivo, Immaculata; Costenbader, Karen H.

2015-01-01

Objective To prospectively examine the association between leukocyte telomere length (LTL) and subsequent RA development in women. Methods Using a case-control design nested within the prospective Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), and Women’s Health Study (WHS), each validated case of RA with a pre-diagnostic blood sample was matched to three controls by cohort, age, menopausal status, postmenopausal hormone therapy, and blood collection covariates. We measured telomere length in genomic DNA extracted from stored buffy coat samples using quantitative PCR. We used unconditional logistic regression to determine odds ratios (OR) and 95% confidence intervals (CI), and random-effects meta-analysis to combine study results. Results In total, we analyzed 296 incident RA cases and 827 matched controls. Mean age of diagnosis among women who developed RA was 60.5 in NHS/NHSII and 61.3 in WHS. Meta-analysis demonstrated that longer pre-diagnostic LTL was associated with increased RA risk when women in the longest vs. shortest LTL tertile were compared (OR=1.51, 95% CI=1.03–2.23; pheterogeneity=0.27). However, statistically significant between study heterogeneity was observed for the intermediate tertile category (pheterogeneity=0.008). We did not observe heterogeneity by menopausal status, inflammatory cytokine levels, age at diagnosis, age at blood collection, body mass index, seropositivity, or HLA-DRB1 shared epitope status. Conclusion Our results do not support a role for short LTL preceding RA development. PMID:26773113

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

Uric acid and serum antioxidant capacity: a reaction to atherosclerosis?

PubMed

Nieto, F J; Iribarren, C; Gross, M D; Comstock, G W; Cutler, R G

2000-01-01

the evidence of a potential beneficial role of antioxidants in preventing atherosclerotic disease is not entirely consistent. to assess the longitudinal association of serum total antioxidant capacity and serum antioxidants with the presence of subclinical carotid atherosclerosis. Prospective case-control study nested within an historical cohort. Cases were 150 individuals with elevated carotid intimal-medial thickness measured by B-mode ultrasound at the first two examinations of the Atherosclerosis Risk in Communities Study (1987-92). Controls were 150 age-gender-matched individuals with low carotid intimal-medial thickness. Serum antioxidant vitamins, uric acid, and serum total antioxidant capacity were measured in frozen serum samples collected from the same individuals in 1974 (13-15 years prior to the determination of case-control status). Compared to controls, atherosclerosis cases had significantly higher levels of serum total antioxidant capacity in 1974 than controls. This difference was almost entirely explained by increased serum concentration of uric acid in cases. In contrast with cross-sectional results, uric acid serum concentration in 1974, was significantly higher in cases than in controls, even after adjusting for the main cardiovascular risk factors. Cases had significantly lower levels of alpha-carotene in the 1974 sera than controls, but no other differences in serum antioxidant vitamin concentrations were observed. The higher serum uric acid concentration seemed associated with elevated total serum antioxidant capacity among individuals with atherosclerosis. This finding is consistent with experimental evidence suggesting that hyperuricemia may be a compensatory mechanism to counteract oxidative damage related to atherosclerosis and aging in humans.

Unconditional or Conditional Logistic Regression Model for Age-Matched Case-Control Data?

PubMed

Kuo, Chia-Ling; Duan, Yinghui; Grady, James

2018-01-01

Matching on demographic variables is commonly used in case-control studies to adjust for confounding at the design stage. There is a presumption that matched data need to be analyzed by matched methods. Conditional logistic regression has become a standard for matched case-control data to tackle the sparse data problem. The sparse data problem, however, may not be a concern for loose-matching data when the matching between cases and controls is not unique, and one case can be matched to other controls without substantially changing the association. Data matched on a few demographic variables are clearly loose-matching data, and we hypothesize that unconditional logistic regression is a proper method to perform. To address the hypothesis, we compare unconditional and conditional logistic regression models by precision in estimates and hypothesis testing using simulated matched case-control data. Our results support our hypothesis; however, the unconditional model is not as robust as the conditional model to the matching distortion that the matching process not only makes cases and controls similar for matching variables but also for the exposure status. When the study design involves other complex features or the computational burden is high, matching in loose-matching data can be ignored for negligible loss in testing and estimation if the distributions of matching variables are not extremely different between cases and controls.

Mismatching between nest volume and clutch volume reduces egg survival and fledgling success in black-tailed gulls

PubMed Central

Yoo, Jeong-Chil

2016-01-01

Abstract A longstanding suggestion posits that parents prefer to match nest volume and clutch size (clutch volume), but few studies have tested this in colonial seabirds that nest in the open. Here, we demonstrate the effects of nest–clutch volume matching on egg survival, hatching, and fledgling success in black-tailed gulls Larus crassirostris on Hongdo Island, Korea. We show that the volume mismatch, defined as the difference between nest volume and total egg volume (the sum of all eggs’ volume in the clutch), was positively related to egg and chick mortality caused by predation, but was not significantly related to hatching success incurred by insulation during the incubation period. Although nest volume was negatively related to laying date, we found that the mismatch was positively related to laying date. Our results support the claim that well-matched nest–clutch volume may contribute to survival of eggs and chicks, and ultimately breeding success. PMID:29491934

Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials.

PubMed

Brentnall, Adam R; Cuzick, Jack; Byers, Helen; Segal, Corrinne; Reuter, Caroline; Detre, Simone; Sestak, Ivana; Howell, Anthony; Powles, Trevor J; Newman, William G; Dowsett, Mitchell

2016-08-01

A case-control study from two randomised breast cancer prevention trials of tamoxifen and raloxifene (P-1 and P-2) identified single-nucleotide polymorphisms (SNPs) in or near genes ZNF423 and CTSO as factors which predict which women will derive most anti-cancer benefit from selective oestrogen receptor modulator (SERM) therapy. In this article, we further examine this question using blood samples from two randomised tamoxifen prevention trials: the International Breast Cancer Intervention Study I (IBIS-I) and the Royal Marsden trial (Marsden). A nested case-control study was designed with 2:1 matching in IBIS-I and 1:1 matching in Marsden. The OncoArray was used for genotyping and included two SNPs previously identified (rs8060157 in ZNF423 and rs10030044 near CTSO), and 102 further SNPs within the same regions. Overall, there were 369 cases and 662 controls, with 148 cases and 268 controls from the tamoxifen arms. Odds ratios were estimated by conditional logistic regression, with Wald 95 % confidence intervals. In the tamoxifen arms, the per-allele odds ratio for rs8060157 was 0.99 (95 %CI 0.73-1.34) and 1.00 (95 %CI 0.76-1.33) for rs10030044. In the placebo arm, the odds ratio was 1.10 (95 %CI 0.87-1.40) for rs8060157 and 1.01 (95 %CI 0.79-1.29) for rs10030044. There was no evidence to suggest that other SNPs in the surrounding regions of these SNPs might predict response to tamoxifen. Results from these two prevention trials do not support the earlier findings. rs8060157 in ZNF423 and rs10030044 near CTSO do not appear to predict response to tamoxifen.

Risk of malignancy with systemic psoriasis treatment in the Psoriasis Longitudinal Assessment Registry.

PubMed

Fiorentino, David; Ho, Vincent; Lebwohl, Mark G; Leite, Luiz; Hopkins, Lori; Galindo, Claudia; Goyal, Kavitha; Langholff, Wayne; Fakharzadeh, Steven; Srivastava, Bhaskar; Langley, Richard G

2017-11-01

The effect of systemic therapy on malignancy risk among patients with psoriasis is not fully understood. Evaluate the impact of systemic treatment on malignancy risk among patients with psoriasis in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Nested case-control analyses were performed among patients with no history of malignancy. Cases were defined as first malignancy (other than nonmelanoma skin cancer) in the Psoriasis Longitudinal Assessment and Registry, and controls were matched by age, sex, geographic region, and time on registry. Study therapies included methotrexate, ustekinumab, and tumor necrosis factor-α (TNF-α) inhibitors. Exposure was defined as 1 or more doses of study therapy within 12 months of malignancy onset and further stratified by duration of therapy. Multivariate conditional logistic regression, adjusted for potential confounders, was used to estimate odds ratios of malignancies associated with therapy. Among 12,090 patients, 252 malignancy cases were identified and 1008 controls were matched. Treatment with methotrexate or ustekinumab for more than 0 months to less than 3 months, 3 months to less than 12 months, or 12 months or longer was not associated with increased malignancy risk versus no exposure. Longer-term (≥12 months) (odds ratio, 1.54; 95% confidence interval, 1.10-2.15; P = .01), but not shorter-term treatment, with a TNF-α inhibitor was associated with increased malignancy risk. Cases and controls could belong to 1 or more therapy categories. Long-term (≥12 months) treatment with a TNF-α inhibitor, but not methotrexate and ustekinumab, may increase risk for malignancy in patients with psoriasis. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2018-05-09

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

Role of matching in case-control studies of antimicrobial resistance.

PubMed

Cerceo, Elizabeth; Lautenbach, Ebbing; Linkin, Darren R; Bilker, Warren B; Lee, Ingi

2009-05-01

Of 57 case-control studies of antimicrobial resistance, matching was used in 23 (40%). Matched variables differed substantially across studies. Of these 23 matched case-control studies, 12 (52%) justified the use of matching, and 9 (39%) noted the strengths or limitations of this approach. Analysis that accounted for matching was performed in only 52% of the case-control studies.

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

Immunodeficiency and the risk of cervical intraepithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV cohort study.

PubMed

Clifford, Gary M; Franceschi, Silvia; Keiser, Olivia; Schöni-Affolter, Franziska; Lise, Mauro; Dehler, Silvia; Levi, Fabio; Mousavi, Mohsen; Bouchardy, Christine; Wolfensberger, Aline; Darling, Katharine E; Staehelin, Cornelia; Bertisch, Barbara; Kuenzli, Esther; Bernasconi, Enos; Pawlita, Michael; Egger, Matthias

2016-04-01

HIV-infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100-cell/μL decrease = 1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR = 1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use = 0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer. © 2015 UICC.

Plasma tea polyphenol levels and subsequent risk of breast cancer among Japanese women: a nested case-control study.

PubMed

Iwasaki, Motoki; Inoue, Manami; Sasazuki, Shizuka; Miura, Tsutomu; Sawada, Norie; Yamaji, Taiki; Shimazu, Taichi; Willett, Walter C; Tsugane, Shoichiro

2010-12-01

Although many in vitro and animal studies have suggested a protective effect of green tea against breast cancer, findings from epidemiological studies have been inconsistent. No study has used prediagnostic biomarkers of tea polyphenols, which might play a protective role. A total of 24,226 women aged 40 to 69 years in the Japan Public Health Center-based Prospective Study who responded to the baseline questionnaire and provided blood in 1990-1995 were followed to December 2002. During a mean 10.6 years of follow-up, 144 newly diagnosed breast cancers were identified. Two matched controls for each case were selected from the cohort. Plasma levels of (-)-epigallocatechin (EGC), (-)-epicatechin (EC), (-)-epigallocatechin-3-gallate (EGCG), and (-)-epicatechin-3-gallate (ECG) were measured, and the odds ratio (OR) of breast cancer according to plasma level was estimated using a conditional logistic regression model. We found no statistically significant association between plasma tea polyphenol levels and breast cancer risk. Adjusted ORs for the highest versus lowest group were 0.90 (95% CI 0.42-1.96; P for trend = 0.98) for EGC, 0.95 (95% CI 0.43-2.08; P for trend = 0.86) for EC, 1.21 (95% CI 0.52-2.80; P for trend = 0.53) for EGCG, and 1.75 (95% CI 0.81-3.78; P for trend = 0.15) for ECG. Stratified analyses according to baseline menopausal status showed no remarkable difference between two strata. This nested case-control study found no overall association between plasma tea polyphenols and the risk of breast cancer in Japan.

Obesity-related hormones and endometrial cancer among postmenopausal women: a nested case-control study within the B~FIT cohort.

PubMed

Dallal, Cher M; Brinton, Louise A; Bauer, Douglas C; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; Lacroix, Andrea; Tice, Jeffrey A; Chia, Victoria M; Falk, Roni; Pfeiffer, Ruth; Pollak, Michael; Veenstra, Timothy D; Xu, Xia; Lacey, James V

2013-02-01

Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case-control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n=15,595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992-1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m(2)), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (OR(T3 vs T1)=2.96; 95% CI, 1.21-7.25; P trend <0.01). After further adjustment for BMI, the estimates were attenuated and the positive trend was no longer statistically significant (OR(T3 vs T1)=2.11; 95% CI, 0.69-6.44; P trend=0.18). No significant associations were observed with adiponectin or HMW adiponectin and endometrial cancer. Our findings with leptin suggest that the leptin-BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity-endometrial cancer associations.

Nested case-control study of night shift work and breast cancer risk among women in the Danish military.

PubMed

Hansen, Johnni; Lassen, Christina F

2012-08-01

Growing but limited evidence suggests that night shift work is associated with breast cancer. The authors conducted a nationwide case-control study nested within a cohort of 18,551 female military employees born in 1929-1968 to investigate the risk for breast cancer after night shift work and to explore the role of leisure time sun exposure and diurnal preference. The authors documented 218 cases of breast cancer (1990-2003) and selected 899 age-matched controls from the cohort by incidence density sampling. Information on shift work, sun exposure habits, diurnal preference and other potential confounders was obtained from a structured questionnaire. ORs were estimated by multivariate conditional logistic regression. Overall, the authors observed an adjusted OR of 1.4 (95% CI 0.9 to 2.1) among women with ever compared with never night shifts. The RR for breast cancer tended to increase with increasing number of years of night shift work (p=0.03) and with cumulative number of shifts (p=0.02),with a neutral risk for fewer than three night shifts per week. The OR for the group with the highest tertile of cumulative exposure was 2.3 (95% CI 1.2 to 4.6). The most pronounced effect of night shift work on breast cancer risk was observed in women with morning chronotype preference and intense night shifts (OR=3.9, 95% CI 1.6 to 9.5). Night shift workers tended to sunbathe more frequently than day workers. The results indicate that frequent night shift work increases the risk for breast cancer and suggest a higher risk with longer duration of intense night shifts. Women with morning preference who worked on night shifts tended to have a higher risk than those with evening preference.

Risk and protective factors for suicide among patients with methamphetamine dependence: a nested case-control study.

PubMed

Kuo, Chian-Jue; Tsai, Shang-Ying; Liao, Ya-Tang; Conwell, Yeates; Lin, Shih-Ku; Chang, Chia-Ling; Chen, Chiao-Chicy; Chen, Wei J

2011-04-01

Methamphetamine as a recreational drug has undergone cycles of popularity, with a recent surge worldwide since the 1990s. This study aimed to identify clinical characteristics associated with suicide mortality in patients with methamphetamine dependence by means of a nested case-control design. In a consecutive series of 1,480 inpatients with methamphetamine dependence (diagnosed according to DSM-III-R and DSM-IV criteria) admitted to a psychiatric center in northern Taiwan from January 1, 1990, through December 31, 2006, 38 deaths due to suicide were identified as cases via record linkage, and 76 controls were randomly selected using risk-set density sampling in a 2:1 ratio, matched for age, sex, and the year of index admission. A standardized chart review process was adopted to collate sociodemographic and clinical information for each study subject. Multivariate conditional logistic regression analysis was used to identify correlates of suicide among these patients. For the sociodemographic and symptom profiles at the latest admission, financial independence lowered the risk for suicide (adjusted risk ratio [ARR] = 0.33, P < .05), whereas visual hallucinations elevated the risk (ARR = 2.57, P < .05) for suicide. For the profiles during the postdischarge period, financial independence (ARR = 0.11, P < .05) remained associated with reduced risk for suicide, whereas suicide attempt (ARR = 8.78, P < .05) and depressive syndrome (ARR = 3.28, P = .059) were associated with increased risk of suicide. Both protective and risk factors for suicide mortality were found among inpatients with methamphetamine dependence, and the findings have implications for clinical intervention and prevention. © Copyright 2011 Physicians Postgraduate Press, Inc.

Case-control study of male germ cell tumors nested in a cohort of car-manufacturing workers: Findings from the occupational history.

PubMed

Langner, Ingo; Schmeisser, Nils; Mester, Birte; Behrens, Thomas; Gottlieb, Andrea; Ahrens, Wolfgang

2010-10-01

To examine whether the previously observed excess risk of male germ cell cancer in a cohort of car-manufacturing workers can be attributed to occupational activities inside and/or outside the car industry. A nested case-control study among workers in six plants included 205 cases of germ cell cancer and 1,105 controls, individually matched by year of birth (±2 years). Job periods of the individual occupational histories were coded based on the International Standard Classification of Occupations (ISCO) and the industrial classification of economic activities (NACE). Odds ratios (ORs) and corresponding 95%-confidence intervals (CI) for ever-never and cumulative employment were calculated by conditional multivariate logistic regression adjusted for cryptorchidism. Significantly increased risks were observed for machinery fitters and assemblers (A) (OR = 1.8, 95% CI 1.25-2.53) and "workers not elsewhere classified" (OR = 2.10, 95% CI 1.27-3.54), but no trend was observed for employment duration in either occupational group. Stratification of job group A by metal-cutting and non-cutting jobs yielded ORs of 1.87 (95% CI 1.31-2.67) and of 1.24 (95% CI 0.68-2.28), respectively. Among "plumbers, welders, sheet & structural metal workers" (adjusted OR 1.4, 95% CI 0.99-1.95) only "structural metal preparers and erectors" showed a substantially increased risk (OR = 2.30; 95% CI 1.27-4.27). Our results do not fully explain the increased incidence of germ cell cancer in the cohort, but support previous findings showing increased risks among metal workers. These risks were most strongly pronounced in metal-cutting activities. © 2010 Wiley-Liss, Inc.

Plasma 25-hydroxyvitamin D3 is associated with decreased risk of postmenopausal breast cancer in whites: a nested case-control study in the multiethnic cohort study.

PubMed

Kim, Yeonju; Franke, Adrian A; Shvetsov, Yurii B; Wilkens, Lynne R; Cooney, Robert V; Lurie, Galina; Maskarinec, Gertraud; Hernandez, Brenda Y; Le Marchand, Loïc; Henderson, Brian E; Kolonel, Laurence N; Goodman, Marc T

2014-01-17

Higher sunlight exposure is correlated with lower incidence of breast cancer in ecological studies, but findings from prospective studies regarding the association of circulating levels of vitamin D with the risk of breast cancer have been null. The objective of this study was to examine the relation between plasma levels of vitamin D and the risk of postmenopausal breast cancer. We conducted a nested case-control study within the Multiethnic Cohort Study of five race/ethnic groups (white, African-American, Native Hawaiian, Japanese, and Latino) from Hawaii and Los Angeles between 2001 and 2006. Pre-diagnostic plasma levels of 25-hydroxyvitamin D2 [25(OH)D2], 25-hydroxyvitamin D3 [25(OH)D3] and 25(OH)D (sum of 25(OH)D2 and 25(OH)D3) were examined among 707 postmenopausal breast cancer cases and matched controls. Using conditional logistic regression models, 20 ng/mL increases of plasma 25(OH)D3 (odds ratio (OR) 0.28; 95% confidence interval (CI) 0.14-0.56) and 25(OH)D (OR 0.43; 95% CI 0.23-0.80) were inversely associated with breast cancer risk among white women, but not among women in other race/ethnic groups. Using two-segmented, piecewise-linear logistic regression models, the change-points of the ORs, either for 25(OH)D3 or for 25(OH)D, were detected as 20 ng/mL among whites. Circulating 25(OH)D3 and 25(OH)D were associated with a reduced risk of postmenopausal breast cancer among whites, but not in other ethnic groups, who reside in low latitude regions.

OPG and sRANKL serum levels and incident hip fracture in postmenopausal Caucasian women in the Women's Health Initiative Observational Study.

PubMed

LaCroix, Andrea Z; Jackson, Rebecca D; Aragaki, Aaron; Kooperberg, Charles; Cauley, Jane A; Chen, Zhao; Leboff, Meryl S; Duggan, David; Wactawski-Wende, Jean

2013-10-01

The osteoprotogerin/receptor activator of NF-kappa β/receptor activator of NF-kappa β ligand (OPG/RANK/RANKL) pathway plays a critical role in bone remodeling. This study investigated associations between serum levels of OPG, soluble RANKL (sRANKL), and the ratio of OPG/sRANKL to risk of incident hip fracture. A nested case-control study was conducted among postmenopausal, Caucasian women aged 50-79 at baseline (1993-1998), followed for hip fracture through March 2005 in the Women's Health Initiative Observational Study. 400 incident hip fracture cases were selected and individually matched to 400 controls with no prior fracture or incident hip fracture. Matching factors were baseline age, enrollment date and hormone therapy (HT) exposure. Baseline serum OPG and sRANKL levels were measured using high sensitivity ELISA. Odds ratios were computed for quartiles of each biomarker adjusting for matching factors and hip fracture risk factors. Serum OPG was significantly associated with older age, low physical activity and poorer physical function in control women. sRANKL was inversely associated with total calcium intake in control women, but not associated with age or other fracture risk factors. The odds ratio for hip fracture comparing the highest to lowest quartiles of OPG was 2.28 (95% confidence interval (CI), 1.45-3.61) after adjusting for the matching variables (p-value for linear trend <0.001), and 1.87 (95% CI, 1.15-3.04; p for linear trend=0.02) after adjusting for self-rated health status, physical activity and physical functioning. No significant associations between sRANKL or the ratio of OPG/sRANKL and hip fracture risk were observed. Serum OPG levels were independently associated with a nearly twofold increased risk of hip fracture in postmenopausal women. Copyright © 2013 Elsevier Inc. All rights reserved.

Blood Erythrocyte Concentrations of Cadmium and Lead and the Risk of B-Cell Non-Hodgkin’s Lymphoma and Multiple Myeloma: A Nested Case-Control Study

PubMed Central

Porta, Miquel; Bergdahl, Ingvar A.; Palli, Domenico; Johansson, Ann-Sofie; Botsivali, Maria; Vineis, Paolo; Vermeulen, Roel; Kyrtopoulos, Soterios A.; Chadeau-Hyam, Marc

2013-01-01

Background Cadmium (Cd) and lead (Pb) are hypothesised to be risk factors for non-Hodgkin’s lymphoma (NHL), a group of haematological malignancies with a suspected environmental aetiology. Within the EnviroGenoMarkers study we utilised pre-diagnostic erythrocyte concentrations of Cd and Pb to determine whether exposure was associated with risk of B-cell NHL and multiple myeloma. Methods 194 incident cases of B-cell NHL and 76 cases of multiple myeloma diagnosed between 1990 and 2006 were identified from two existing cohorts; EPIC-Italy and the Northern Sweden Health and Disease Study. Cases were matched to healthy controls by centre, age, gender and date of blood collection. Cd and Pb were measured in blood samples provided at recruitment using inductively coupled plasma-mass spectrometry. Logistic regression was applied to assess the association with risk. Analyses were stratified by cohort and gender and by subtype where possible. Results There was little evidence of an increased risk of B-cell NHL or multiple myeloma with exposure to Cd (B-cell NHL: OR 1.09 95%CI 0.61, 1.93, MM: OR 1.16 95% CI: 0.40, 3.40 ) or Pb (B-cell NHL: 0.93 95% CI 0.43, 2.02, multiple myeloma: OR 1.63 95%CI 0.45, 5.94) in the total population when comparing the highest to the lowest quartile of exposure. However, gender and cohort specific differences in results were observed. In females the risk of B-cell NHL was more than doubled in those with a body burden of Cd >1µg/L (OR 2.20 95%CI; 1.04, 4.65). Conclusions This nested case-control study does not support a consistent positive association between Cd or Pb and NHL, but there is some indication of a gender specific effect suggesting further research is warranted. PMID:24312375

Risk factors for hyperkalaemia in a cohort of patients with newly diagnosed heart failure: a nested case-control study in UK general practice.

PubMed

Michel, Alexander; Martín-Pérez, Mar; Ruigómez, Ana; García Rodríguez, Luis A

2015-02-01

The aim of this study was to identify risk factors for hyperkalaemia in a cohort of patients with newly diagnosed heart failure in the UK. A nested case-control study was conducted using data from The Health Improvement Network primary care database. A cohort of 19 194 patients aged 1-89 years between January 2000 and December 2005 with newly diagnosed heart failure was followed up and cases of hyperkalaemia identified. Cases were frequency matched to controls by age, sex, and calendar year, and information on demographics, co-morbidities, co-medications, and lifestyle factors was extracted from the database. Using unconditional logistic regression models, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to identify potential risk factors. In total, 2176 hyperkalaemia cases were identified over a mean follow-up of 3.9 years. Significant risk factors for hyperkalaemia were: renal failure (OR 3.81; 95% CI 3.29-4.42), type II diabetes (OR 1.52; 95% CI 1.31-1.75), valvular heart disease (OR 1.28; 95% CI 1.06-1.54), and current use of potassium-sparing diuretics (OR 3.01; 95% CI 2.61-3.48), ACE inhibitors (OR 1.70; 95% CI 1.41-2.04), trimethoprim (OR 2.82; 95% CI 1.88-4.23), non-steroidal anti-inflammatory drugs (OR 1.41; 95% CI 1.11-1.79), and several drug combinations. The risk was highest within the first month of medication use and decreased thereafter. Our findings may help to better identify patients with heart failure most likely to benefit from careful monitoring of serum potassium levels. Particular vigilance is needed during the start of treatment with certain medications. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.

Somatic mutations in benign breast disease tissue and risk of subsequent invasive breast cancer.

PubMed

Rohan, Thomas E; Miller, Christopher A; Li, Tiandao; Wang, Yihong; Loudig, Olivier; Ginsberg, Mindy; Glass, Andrew; Mardis, Elaine

2018-06-06

Insights into the molecular pathogenesis of breast cancer might come from molecular analysis of tissue from early stages of the disease. We conducted a case-control study nested in a cohort of women who had biopsy-confirmed benign breast disease (BBD) diagnosed between 1971 and 2006 at Kaiser Permanente Northwest and who were followed to mid-2015 to ascertain subsequent invasive breast cancer (IBC); cases (n = 218) were women with BBD who developed subsequent IBC and controls, individually matched (1:1) to cases, were women with BBD who did not develop IBC in the same follow-up interval as that for the corresponding case. Targeted sequence capture and sequencing were performed for 83 genes of importance in breast cancer. There were no significant case-control differences in mutation burden overall, for non-silent mutations, for individual genes, or with respect either to the nature of the gene mutations or to mutational enrichment at the pathway level. For seven subjects with DNA from the BBD and ipsilateral IBC, virtually no mutations were shared. This study, the first to use a targeted multi-gene sequencing approach on early breast cancer precursor lesions to investigate the genomic basis of the disease, showed that somatic mutations detected in BBD tissue were not associated with breast cancer risk.

Association of benzodiazepine and Z-drug use with the risk of hospitalisation for fall-related injuries among older people: a nationwide nested case-control study in Taiwan.

PubMed

Yu, Nan-Wen; Chen, Pei-Jung; Tsai, Hui-Ju; Huang, Chih-Wan; Chiu, Yu-Wen; Tsay, Wen-Ing; Hsu, Jui; Chang, Chia-Ming

2017-07-11

Non-benzodiazepine hypnotics (Z-drugs) are advocated to be safer than benzodiazepines (BZDs). This study comprehensively investigated the association of BZD and Z-drug usage with the risk of hospitalisation for fall-related injuries in older people. This study used the Taiwan National Health Insurance Database with a nested matched case-control design. We identified 2238 elderly patients who had been hospitalised for fall-related injuries between 2003 and 2012. They were individually matched (1:4) with a comparison group by age, sex, and index year. Conditional logistic regression was used to determine independent effects of drug characteristics (type of exposure, dosage, half-life, and polypharmacy) on older people. Older people hospitalisation for fall-related injuries were significantly associated with current use of BZDs (adjusted odds ratio [AOR] = 1.32, 95% confidential interval [CI] = 1.17-1.50) and Z-drugs (AOR = 1.24, 95%CI = 1.05-1.48). At all dose levels of BZDs, high dose levels of Z-drugs, long-acting BZD, and short-acting BZD use were all significantly increased the risk of fall-related injuries requiring hospitalisation. Polypharmacy, the use of two or more kinds of BZDs, one kind of BZD plus Z-drugs and two or more kinds of BZDs plus Z-drugs, also significantly increased the risk (AOR = 1.61, 95% CI = 1.38-1.89; AOR = 1.65, 95% CI = 1.08-2.50, and AOR = 1.58, 95% CI = 1.21-2.07). Different dose levels and half-lives of BZDs, a high dose of Z-drugs, and polypharmacy with BZDs and Z-drugs were associated with an increased risk of fall-related injury requiring hospitalisation in older people. Physicians should balance the risks and benefits when prescribing these drug regimens to older people considering the risk of falls.

A prospective study of serum soluble CD30 concentration and risk of non-Hodgkin lymphoma

PubMed Central

Lan, Qing; Martinez-Maza, Otoniel; Oken, Martin M.; Hocking, William; Huang, Wen-Yi; Baris, Dalsu; Conde, Betty; Rothman, Nathaniel

2009-01-01

Prediagnostic serum concentration of soluble CD30 (sCD30), a marker for chronic B-cell stimulation, has been associated with increased risk of developing AIDS-related non-Hodgkin lymphoma (NHL) in a recent study of HIV+ patients. To investigate among healthy persons whether serum sCD30 is associated with NHL risk, we carried out a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. There was a strong dose-response relationship between prediagnostic sCD30 concentration and NHL risk among 234 cases and 234 individually matched controls (odds ratio [95% confidence interval] for second, third, and fourth quartiles vs first quartile: 1.4 [0.8-2.6], 2.2 [1.2-4.1], 4.1 [2.2-7.8]; Ptrend < .001), which persisted among cases diagnosed 6 to 10 years after providing a blood sample. Given that a similar relationship has been observed among HIV+ patients, our findings suggest that chronic B-cell stimulation may be an important mechanism involved in B-cell lymphomagenesis among severely immunocompromised and healthy populations alike. PMID:19638620

Trajectory of cartilage loss within 4 years of knee replacement--a nested case-control study from the osteoarthritis initiative.

PubMed

Eckstein, F; Boudreau, R M; Wang, Z; Hannon, M J; Wirth, W; Cotofana, S; Guermazi, A; Roemer, F; Nevitt, M; John, M R; Ladel, C; Sharma, L; Hunter, D J; Kwoh, C K

2014-10-01

Knee replacement (KR) represents a clinically important endpoint of knee osteoarthritis (KOA). Here we examine the 4-year trajectory of femoro-tibial cartilage thickness loss prior to KR vs non-replaced controls. A nested case-control study was performed in Osteoarthritis Initiative (OAI) participants: Cases with KR between 12 and 60 month (M) follow-up were each matched with one control (without KR through 60M) by age, sex, and baseline radiographic stage. Femoro-tibial cartilage thickness was measured quantitatively using magnetic resonance imaging (MRI) at the annual visit prior to KR occurrence (T0), and at 1-4 years prior to T0 (T-1 to T-4). Cartilage loss between cases and controls was compared using paired t-tests and conditional logistic regression. One hundred and eighty-nine knees of 164 OAI participants [55% women; age 64 ± 8.7; body mass index (BMI) 29 ± 4.5] had KR and longitudinal cartilage data. Comparison of annualized slopes of change across all time points revealed greater loss in the central medial tibia (primary outcome) in KRs than in controls [94 ± 137 vs 55 ± 104 μm; P = 0.0017 (paired t); odds ratio (OR) 1.36 (95% confidence interval (CI): 1.08-1.70)]. The discrimination was stronger for T-2 → T0 [OR 1.61 (1.33-1.95), n = 127] than for T-1 → T0, and was not statistically significant for intervals prior to T-2 [i.e., T-4 → T-2, OR 0.97 (0.67-1.41), n = 60]. Results were similar for total medial femoro-tibial cartilage loss (secondary outcome), and when adjusting for pain and BMI. In knees with subsequent replacement, cartilage loss accelerates in the 2 years, and particularly in the year prior to surgery, compared with controls. Whether slowing this cartilage loss can delay KR remains to be determined. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients: results of the INSIGHT case-control study.

PubMed

van Velzen, A S; Eckhardt, C L; Peters, M; Leebeek, F W G; Escuriola-Ettingshausen, C; Hermans, C; Keenan, R; Astermark, J; Male, C; Peerlinck, K; le Cessie, S; van der Bom, J G; Fijnvandraat, K

2017-07-01

Essentials Research suggests that intensive treatment episodes may increase the risk to develop inhibitors. We performed an international nested case-control study with 298 non-severe hemophilia A patients. Surgery and a high dose of factor VIII concentrate were associated with increased inhibitor risk. Physicians need to review arguments for factor VIII dose and elective surgery extra critically. Background Inhibitor development is a major complication of treatment with factor VIII concentrates in hemophilia. Findings from studies among severe hemophilia A patients suggest that intensive treatment episodes increase the risk of developing inhibitors. Objectives We set out to assess whether intensive treatment is also associated with an increased risk of inhibitor development among non-severe hemophilia A patients. Patients/Methods We performed a nested case-control study. A total of 75 inhibitor patients (cases) and 223 control patients were selected from 2709 non-severe hemophilia A patients (FVIII:C, 2-40%) of the INSIGHT cohort study. Cases and controls were matched for date of birth and cumulative number of exposure days (EDs) to FVIII concentrates. Conditional logistic regression was used to calculate both unadjusted and adjusted odds ratios (aOR); the latter were adjusted for a priori specified confounders. Results Peak treatment of 5 or 10 consecutive EDs did not increase inhibitor risk (aOR, 1.0; 95% confidence interval (CI), 0.4-2.5; and aOR, 1.8; CI, 0.6-5.5, respectively). Both surgical intervention (aOR, 4.2; CI, 1.7-10.3) and a high mean dose (> 45 IU kg -1 /ED) of FVIII concentrate (aOR, 7.5; CI, 1.6-35.6) were associated with an increased inhibitor risk. Conclusions Our findings suggest that high-dose FVIII treatment and surgery increase the risk of inhibitor development in non-severe hemophilia A. Together with the notion that non-severe hemophilia A patients are at a lifelong risk of inhibitor development, we suggest that in the future physicians will review the arguments for the FVIII dose and elective surgery extra critically. © 2017 International Society on Thrombosis and Haemostasis.

Inclusion of persons with disabilities in systems of social protection: a population-based survey and case-control study in Peru.

PubMed

Bernabe-Ortiz, Antonio; Diez-Canseco, Francisco; Vasquez, Alberto; Kuper, Hannah; Walsham, Matthew; Blanchet, Karl

2016-08-26

This study aims to assess the needs of people with disabilities and their level of inclusion in social protection programmes. Population based-survey with a nested case-control study. Morropon, a semiurban district located in Piura, northern Peru. For the population survey, a two-stage sampling method was undertaken using data from the most updated census available and information of each household member aged ≥5 years was collected. In the nested case-control study, only one participant, case or control, per household was included in the study. Disability was screened using the Washington Group short questionnaire. A case, defined as an individual aged ≥5 years with disabilities, was matched with one control without disabilities by sex and age (±5 years). Information was collected on socioeconomic status, education, health and rehabilitation and social protection participation. The survey included 3684 participants, 1848 (50.1%) females, mean age: 36.4 (SD: 21.7). A total of 290 participants (7.9%; 95% CI 7.0% to 8.7%) were classified as having disability. Adults with disabilities were more likely to be single (OR=3.40; 95% CI 1.54 to 7.51) and not to be working (OR=4.36; 95% CI 2.26 to 8.40), while those who did work were less likely to receive the national minimum wage (ie, 750 PEN or about US$265; p=0.007). People with disabilities were more likely to experience health problems. There was no difference between those enrolled in any social protection programme among participants with and without disabilities. People with disabilities were found to have higher needs for social protection, but were not more likely to be enrolled in social protection programmes. The Peruvian social protection system should consider adding disability status to selection criteria in their cash transfer programmes as well as implementing disability-specific interventions. 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/

Cancer complicating systemic lupus erythematosus--a dichotomy emerging from a nested case-control study.

PubMed

Dey, D; Kenu, E; Isenberg, D A

2013-08-01

We determined whether any individual cancers are increased or decreased in a cohort of 595 patients with systemic lupus erythematosus (SLE) followed for up to 32 years at the University College London Hospitals Lupus Clinic, looking for any associated clinical or serological factors and the prognosis after cancer diagnosis. We undertook a careful retrospective review of the medical records and identified all individuals diagnosed with cancer. For controls, we selected three other patients in the cohort who had not developed cancer, carefully matched for age, sex, ethnicity and disease duration, to determine if any obvious differences emerged in a nested case-control design. Thirty-three patients developed cancer after being diagnosed with SLE. There was a statistically insignificant small increase in overall cancer risk, standardized incidence ratios (SIRs) 1.05 (95% CI 0.52-1.58) and increased SIRs for cervical, prostate, anal and pancreatic cancers and reduction in breast cancer SIRs. Haematological and musculoskeletal manifestations, anticardiolipin and antithyroid globulin antibodies were found to be positively associated with cancer risk in multivariate analysis. There was no drug, dose or duration was associated with cancer risk. There was a reduction in survival with a cancer fatality rate of 84.2% (p < 0.0001). We found a very small but statistically insignificant increased cancer risk with reduction in survival. Whereas some cancers appear to be more common in SLE, notably prostate and cervical cancer, others, particularly breast cancer, are less frequent. Multiple clinical and serological factors are involved in the increased risk of malignancy in SLE. No drug dose or duration effect was identified.

NO2, as a marker of air pollution, and recurrent wheezing in children: a nested case-control study within the BAMSE birth cohort

PubMed Central

Emenius, G; Pershagen, G; Berglind, N; Kwon, H; Lewne, M; Nordvall, S; Wickman, M

2003-01-01

Aims: To investigate the association between air pollution, including with NO2, and recurrent wheezing during the first two years of life. Methods: A birth cohort (BAMSE) comprised 4089 children, for whom information on exposures, symptoms, and diseases was available from parental questionnaires at ages 2 months, and 1 and 2 years. NO2 was measured during four weeks in and outside the dwellings of children with recurrent wheezing and two age matched controls, in a nested case-control study (540 children). Results: Conditional logistic regression showed an OR of 1.60 (95% CI 0.78 to 3.26) among children in the highest quartile of outdoor NO2 exposure in relation to those in the lowest quartile, adjusted for potential confounders. The corresponding OR for indoor NO2 was 1.51 (95% CI 0.81 to 2.82). An interaction with environmental tobacco smoke (ETS) was indicated with an OR of 3.10 (95% CI 1.32 to 7.30) among children exposed to the highest quartile of indoor NO2 and ETS. The association between NO2 and recurrent wheezing appeared stronger in children who did not fulfil the criteria for recurrent wheezing until their second year. Conclusions: Although the odds of increased recurrent wheezing are not statistically significantly different from one, results suggest that exposure to air pollution including NO2, particularly in combination with exposure to ETS, increases the risk of recurrent wheezing in children. PMID:14573719

Non-Steroidal Anti-Inflammatory Drug Use and the Risk of Acute Myocardial Infarction in the General German Population: A Nested Case-Control Study.

PubMed

Thöne, Kathrin; Kollhorst, Bianca; Schink, Tania

2017-09-01

Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with an increased relative risk of acute myocardial infarction (AMI), but the label warnings refer particularly to patients with cardiovascular risk factors. The magnitude of relative AMI risk for patients with and without cardiovascular risk factors varies between studies depending on the drugs and doses studied. The aim of our study was to estimate population-based relative AMI risks for individual and widely used NSAIDs, for a cumulative amount of NSAID use, and for patients with and without a prior history of cardiovascular risk factors. Based on data from the German Pharmacoepidemiological Research Database (GePaRD) of about 17 million insurance members from four statutory health insurance providers, for the years 2004-2009, a nested case-control study was conducted within a cohort of 3,476,931 new NSAID users classified into current, recent, or past users. Up to 100 controls were matched to each case by age, sex, and length of follow-up using risk set sampling. Multivariable conditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Duration of NSAID use was calculated by the cumulative amount of dispensed defined daily doses (DDDs), and stratified analyses were conducted for potential effect modifiers. Overall, 17,236 AMI cases were matched to 1,714,006 controls. Elevated relative AMI risks were seen for current users of fixed combinations of diclofenac with misoprostol (OR 1.76, 95% CI 1.26-2.45), indometacin (1.69, 1.22-2.35), ibuprofen (1.54, 1.43-1.65), etoricoxib (1.52, 1.24-1.87), and diclofenac (1.43, 1.34-1.52) compared with past use. A low cumulative NSAID amount was associated with a higher relative AMI risk for ibuprofen, diclofenac, and indometacin. The relative risk associated with current use of diclofenac, fixed combinations of diclofenac with misoprostol, etoricoxib, and ibuprofen was highest in the younger age group (<60 years) and similar for patients with or without major cardiovascular risk factors. Relative AMI risk estimates differed among the 15 investigated individual NSAIDs. Diclofenac and ibuprofen, the most frequently used NSAIDs, were associated with a 40-50% increased relative risk of AMI, even for low cumulative NSAID amounts. The relative AMI risk in patients with and without cardiovascular risk factors was similarly elevated.

Plasma bicarbonate and odds of incident hypertension.

PubMed

Mandel, Ernest I; Forman, John P; Curhan, Gary C; Taylor, Eric N

2013-12-01

Several biomarkers of metabolic acidosis, including lower plasma bicarbonate, have been associated with prevalent hypertension in cross-sectional studies. We sought to examine prospectively whether lower plasma bicarbonate is associated with incident hypertension. We conducted a prospective case-control study nested within the Nurses' Health Study II. Plasma bicarbonate was measured in 695 nonobese women without hypertension at time of blood draw who subsequently developed hypertension during 6 years of follow-up. Control subjects were matched to case subjects according to age, race, time and day of blood draw, and day of menstrual cycle. We used unconditional logistic regression to generate odds ratios (ORs) for development of hypertension by quintile of baseline plasma bicarbonate. After adjusting for matching factors, body mass index, family history of hypertension, plasma creatinine, and dietary and lifestyle factors, higher plasma bicarbonate was associated with lower odds of developing hypertension across quintiles (P for linear trend = 0.04). Those in the highest compared with the lowest quintile of plasma bicarbonate had 31% lower odds of developing hypertension (OR = 0.69; 95% confidence interval = 0.48-0.99). Further adjustment for diet-estimated net endogenous acid production, plasma insulin, 25-hydroxyvitamin D, and uric acid did not alter these findings. Our case-control study is consistent with a modest association between higher plasma bicarbonate and reduced odds of developing hypertension among nonobese women, although our findings are of borderline statistical significance. Further research is required to confirm this finding as part of a larger prospective cohort study and to elucidate the mechanism for this relation.

Trimethoprim/sulfamethoxazole-induced phenytoin toxicity in the elderly: a population-based study

PubMed Central

Antoniou, Tony; Gomes, Tara; Mamdani, Muhammad M; Juurlink, David N

2011-01-01

AIMS Pharmacokinetic studies suggest that trimethoprim (TMP) can inhibit the hepatic metabolism of phenytoin, but the clinical relevance of this is uncertain. We studied the risk of phenytoin toxicity following the prescription of trimethoprim/sulfamethoxazole (TMP/SMX), a commonly used antibiotic, among elderly patients receiving phenytoin. METHODS We conducted a population-based, nested case–control study of a cohort of Ontario residents aged 66 years of age or older treated with phenytoin over a 17-year period (April 1 1992 to March 31 2009). Within this group, case patients were those hospitalized with phenytoin toxicity. For each case, we identified up to four control patients from the same cohort, matched for age and sex, and determined the odds ratio (OR) for the association between phenytoin toxicity and receipt of TMP/SMX in the preceding 30 days. RESULTS Among 58 429 elderly patients receiving phenytoin during the study period, we identified 796 case patients hospitalized for phenytoin toxicity and 3148 matched controls. Following multivariable adjustment for potential confounders, we observed a more than doubling of the risk of phenytoin toxicity following the receipt of TMP/SMX [adjusted OR 2.11, 95% confidence interval (CI) 1.24, 3.60]. In contrast, we observed no such risk with amoxicillin, an antibiotic with similar indications but not expected to interact with phenytoin (adjusted OR 1.12, 95% CI 0.64, 1.98). CONCLUSION Among older patients receiving phenytoin, treatment with TMP/SMX is associated with a more than twofold increase in the risk of phenytoin toxicity. When clinically appropriate, alternate antibiotics should be considered for these patients. PMID:21395647

25-Hydroxy vitamin-D, obesity, and associated variables as predictors of breast cancer risk and tamoxifen benefit in NSABP-P1.

PubMed

Amir, Eitan; Cecchini, Reena S; Ganz, Patricia A; Costantino, Joseph P; Beddows, Samantha; Hood, Nicola; Goodwin, Pamela J

2012-06-01

Observational studies suggest that host factors are associated with breast cancer risk. The influence of obesity, vitamin-D status, insulin resistance, inflammation, and elevated adipocytokines in women at high risk of breast cancer is unknown. The NSABP-P1 trial population was used for a nested case-control study. Cases were drawn from those who developed invasive breast cancer and controls selected from unaffected participants (≤4 per case) matched for age, race, 5 year Gail score, and geographic location of clinical center as a surrogate for latitude. Fasting serum banked at trial enrolment was assayed for 25-hydroxy vitamin-D (25OHD), insulin, leptin (adipocytokine), and C-reactive protein (CRP, marker of inflammation). Logistic regression was used to test for associations between study variables and the risk of invasive breast cancer. Two hundred and thirty-one cases were matched with 856 controls. Mean age was 54, and 49% were premenopausal. There were negative correlations for 25OHD with body mass index (BMI), insulin, CRP, and leptin. BMI ≥ 25 kg/m(2) was associated with higher breast cancer risk (odds ratio [OR] 1.45, p = 0.02) and tamoxifen treatment was associated with lower risk (OR = 0.44, p < 0.001). Suboptimal 25OHD (<72 nmol/l) did not influence breast cancer risk (OR = 1.06, p = 0.76). When evaluated as continuous variables, 25OHD, insulin, CRP, and leptin levels were not associated with breast cancer risk (all p > 0.34). In this high risk population, higher BMI was associated with a greater breast cancer risk. Serum levels of 25OHD, insulin, CRP, and leptin were not independent predictors of either breast cancer risk or tamoxifen benefit.

The effect of past antibiotic exposure on diabetes risk

PubMed Central

Boursi, Ben; Mamtani, Ronac; Haynes, Kevin; Yang, Yu-Xiao

2015-01-01

Objective Gut microbiota influence metabolic pathways relevant to the pathogenesis of obesity, insulin-resistance and diabetes. Antibiotic therapy can alter the microbiota and is commonly used in western countries. We sought to evaluate whether past antibiotic exposure increases diabetes risk. Research design and methods We conducted a nested case-control study using a large population-based database from the United Kingdom (UK). Cases were defined as those with incident diagnosis of diabetes. For every case, 4 eligible controls matched on age, sex, practice-site, and duration of follow-up before index-date were selected using incidence-density sampling. Exposure of interest was antibiotic therapy >1 year before index-date. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. The risk was adjusted for body mass index (BMI), smoking, last glucose level and number of infections before index-date, as well as past medical history of coronary artery disease and hyperlipidemia. Results The study included 208,002 diabetic cases and 815,576 matched controls. Exposure to a single antibiotic prescription was not associated with higher adjusted diabetes risk. Treatment with 2–5 antibiotic courses was associated with increase in diabetic risk for penicillin, cephalosporins, macrolides and quinolones with adjusted OR ranging from 1.08 (95%CI 1.05–1.11) for penicillin to 1.15 (95%CI 1.08–1.23) for quinolones. The risk increased with the number of antibiotic courses and reached 1.37 (95%CI 1.19–1.58) for >5 courses of quinolones. There was no association between exposure to anti-virals and anti-fungals and diabetes risk. Conclusions Exposure to certain antibiotic groups increases diabetes risk. PMID:25805893

Association between traditional systemic antipsoriatic drugs and tuberculosis risk in patients with psoriasis with or without psoriatic arthritis: results of a nationwide cohort study from Taiwan.

PubMed

Chen, Yi-Ju; Wu, Chun-Ying; Shen, Jui-Lung; Chen, Tzu-Ting; Chang, Yun-Ting

2013-07-01

Although the link between tuberculosis (TB) and biologics use is well established, the risk of TB among patients with psoriasis exposed to traditional systemic therapies remains elusive. The aim is to investigate the association between traditional systemic therapies and TB among patients with psoriasis. We conducted a retrospective cohort study on the risk of active TB among patients with psoriasis and psoriatic arthritis, using the National Health Insurance Research Database of Taiwan, 1996 through 2008. Standardized incidence ratios of TB were analyzed in comparison with age- and gender-matched general population. Logistic regression was used in a nested case-control analysis to estimate the odds ratios of TB related to exposure to traditional systemic agents during the year before TB development. Among the 81,266 patients in the psoriasis cohort, 497 new active TB cases were identified. The incidence rate of TB was 102 cases per 100,000 person-years among patients with psoriasis (standardized incidence ratio 1.22, 95% confidence interval 1.18-1.33). The risk of TB was higher in patients with severe disease (standardized incidence ratio 1.52, 95% confidence interval 1.46-1.74). To facilitate comparisons with the 497 active TB cases, a total of 1988 matched control subjects were selected for a nested case-control study. Patients taking systemic corticosteroids and nonsteroidal anti-inflammatory drugs were associated with higher incidence of TB, especially frequent users, after adjustment for multiple TB risk factors, drug exposures, hospital visits, and level of urbanization. Stratified analyses of current users and new users of these drugs revealed similar results. Finally, traditional systemic antipsoriatic treatment was not associated with TB on any of the analyses. The National Health Insurance Research Database did not contain information regarding severity of psoriasis, smoking status, alcohol use, diet, laboratory parameters, chest radiograph, or history of recent contact with an individual with TB. Misclassification of disease cannot be ruled out in a registry-based database. The accessibility of health care may be associated with the level of urbanization, which could confound the effect of drugs in multivariate analyses. Severe psoriasis may be associated with an elevated TB risk. Traditional systemic therapies do not seem to be strongly associated with TB occurrence. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Human Exposure to Endocrine-Disrupting Chemicals and Prenatal Risk Factors for Cryptorchidism and Hypospadias: A Nested Case–Control Study

PubMed Central

Fernandez, Mariana F.; Olmos, Begoña; Granada, Alicia; López-Espinosa, Maria José; Molina-Molina, José-Manuel; Fernandez, Juan Manuel; Cruz, Milagros; Olea-Serrano, Fátima; Olea, Nicolás

2007-01-01

Background Exposure to xenoestrogens during pregnancy may disturb the development and function of male sexual organs. Objective In this study we aimed to determine whether the combined effect of environmental estrogens measured as total effective xenoestrogen burden (TEXB) is a risk factor for male urogenital malformations. Methods In a case–control study, nested in a mother–child cohort (n = 702) established at Granada University Hospital, we compared 50 newborns with diagnosis of cryptorchidism and/or hypospadias with 114 boys without malformations matched by gestational age, date of birth, and parity. Controls did not differ from the total cohort in confounding variables. TEXB and levels of 16 organochlorine pesticides were measured in placenta tissues. Characteristics of parents, pregnancy, and birth were gathered by questionnaire. We used conditional and unconditional regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results TEXB from organohalogenated compounds was detectable in 72% and 54% of case and control placentas, respectively. Compared with controls, cases had an OR for detectable versus non-detectable TEXB of 2.82 (95% CI, 1.10–7.24). More pesticides were detected in cases than in controls (9.34 ± 3.19 vs. 6.97 ± 3.93). ORs for cases with detectable levels of pesticides, after adjusting for potential confounders in the conditional regression analysis, were o,p′-DDT (OR = 2.25; 95% CI, 1.03–4.89), p,p′-DDT (OR = 2.63; 95% CI, 1.21–5.72), lindane (OR = 3.38; 95% CI, 1.36–8.38), mirex (OR = 2.85; 95% CI, 1.22–6.66), and endosulfan alpha (OR = 2.19; 95% CI, 0.99–4.82). Engagement of mothers in agriculture (OR = 3.47; 95% CI, 1.33–9.03), fathers’ occupational exposure to xenoestrogens (OR = 2.98; 95% CI, 1.11–8.01), and history of previous stillbirths (OR = 4.20; 95% CI, 1.11–16.66) were also associated with risk of malformations. Conclusions We found an increased risk for male urogenital malformations related to the combined effect of environmental estrogens in placenta. PMID:18174944

Second Malignant Neoplasms in Digestive Organs After Childhood Cancer: A Cohort-Nested Case-Control Study

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

Tukenova, Markhaba; Diallo, Ibrahima; University Paris Sud 11, UMRS, Villejuif

Purpose: Cancers of the digestive system constitute a major risk for childhood cancer survivors treated with radiotherapy once they reach adulthood. The aim of this study was to determine therapy-related risk factors for the development of a second malignancy in the digestive organs (SMDO) after a childhood cancer. Methods and Materials: Among 4,568 2-year survivors of a childhood solid cancer diagnosed before 17 years of age at eight French and British centers, and among 25,120 patients diagnosed as having a malignant neoplasm before the age of 20 years, whose data were extracted from the Nordic Cancer Registries, we matched 58more » case patients (41 men and 17 women) of SMDO and 167 controls, in their respective cohort, for sex, age at first cancer, calendar year of occurrence of the first cancer, and duration of follow-up. The radiation dose received at the site of each second malignancy and at the corresponding site of its matched control was estimated. Results: The risk of developing a SMDO was 9.7-fold higher in relation to the general populations in France and the United Kingdom. In the case-control study, a strong dose-response relationship was estimated, compared with that in survivors who had not received radiotherapy; the odds ratio was 5.2 (95% CI, 1.7-16.0) for local radiation doses between 10 and 29 Gy and 9.6 (95% CI, 2.6-35.2) for doses equal to or greater than 30 Gy. Chemotherapy was also found to increase the risk of developing SMDO. Conclusions: This study confirms that childhood cancer treatments strongly increase the risk of SMDO, which occur only after a very long latency period.« less

Lysophosphatidic Acid and Apolipoprotein A1 Predict Increased Risk of Developing World Trade Center Lung Injury: A Nested Case-Control Study

PubMed Central

Tsukiji, Jun; Cho, Soo Jung; Echevarria, Ghislaine C.; Kwon, Sophia; Joseph, Phillip; Schenck, Edward J.; Naveed, Bushra; Prezant, David J.; Rom, William N.; Schmidt, Ann Marie; Weiden, Michael D.; Nolan, Anna

2014-01-01

Rationale Metabolic syndrome, inflammatory and vascular injury markers measured in serum after WTC exposures predict abnormal FEV1. We hypothesized that elevated LPA levels predict FEV1

Calcium Channel Blockers in Secondary Cardiovascular Prevention and Risk of Acute Events: Real-World Evidence from Nested Case-Control Studies on Italian Hypertensive Elderly.

PubMed

Bettiol, Alessandra; Lucenteforte, Ersilia; Vannacci, Alfredo; Lombardi, Niccolò; Onder, Graziano; Agabiti, Nera; Vitale, Cristiana; Trifirò, Gianluca; Corrao, Giovanni; Roberto, Giuseppe; Mugelli, Alessandro; Chinellato, Alessandro

2017-12-01

Antihypertensive treatment with calcium channel blockers (CCBs) is consolidated in clinical practice; however, different studies observed increased risks of acute events for short-acting CCBs. This study aimed to provide real-world evidence on risks of acute cardiovascular (CV) events, hospitalizations and mortality among users of different CCB classes in secondary CV prevention. Three case-control studies were nested in a cohort of Italian elderly hypertensive CV-compromised CCBs users. Cases were subjects with CV events (n = 25,204), all-cause hospitalizations (n = 19,237), or all-cause mortality (n = 17,996) during the follow-up. Up to four controls were matched for each case. Current or past exposition to CCBs at index date was defined based on molecule, formulation and daily doses of the last CCB delivery. The odds ratio (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. Compared to past users, current CCB users had significant reductions in risks of CV events [OR 0.88 (95% CI: 0.84-0.91)], hospitalization [0.90 (0.88-0.93)] and mortality [0.48 (0.47-0.49)]. Current users of long-acting dihydropyridines (DHPs) had the lowest risk [OR 0.87 (0.84-0.90), 0.86 (0.83-0.90), 0.55 (0.54-0.56) for acute CV events, hospitalizations and mortality], whereas current users of short-acting CCBs had an increased risk of acute CV events [OR 1.77 (1.13-2.78) for short-acting DHPs; 1.19 (1.07-1.31) for short-acting non-DHPs] and hospitalizations [OR 1.84 (0.96-3.51) and 1.23 (1.08-1.42)]. The already-existing warning on short-acting CCBs should be potentiated, addressing clinicians towards the choice of long-acting formulations.

Liver cancer risk, coffee, and hepatitis C virus infection: a nested case–control study in Japan

PubMed Central

Wakai, K; Kurozawa, Y; Shibata, A; Fujita, Y; Kotani, K; Ogimoto, I; Naito, M; Nishio, K; Suzuki, H; Yoshimura, T; Tamakoshi, A

2007-01-01

We examined hepatocellular carcinoma mortality in relation to coffee consumption and anti-hepatitis C virus (HCV) antibody seropositivity in a nested case–control study involving 96 cases. The multivariate-adjusted odds ratios (95% confidence interval) for daily coffee drinkers vs non-drinkers were 0.49 (0.25–0.96), 0.31 (0.11–0.85), and 0.75 (0.29–1.92) in all cases, in HCV-positive and in HCV-negative individuals, respectively. PMID:17637681

Dietary vitamin A and lung cancer: results of a case-control study among chemical workers.

PubMed

Bond, G G; Thompson, F E; Cook, R R

1987-01-01

A nested case-control study conducted among a cohort of chemical manufacturing employees provided an opportunity to test the hypothesis that lung cancer risk is inversely related to dietary intake of vitamin A. Eligible for study were 308 former male employees who had died of lung cancer between 1940 and 1980. Two control groups, one a decedent and the other a "living" series, were individually matched to the cases one-for-one. Interviews were completed with 734 subjects or their next-of-kin and included a food frequency list. A vitamin A index was developed for each subject based on the frequency of consumption of 29 food items. After adjustment for a number of potentially confounding variables (e.g., smoking, educational level, and use of vitamin supplements), there was evidence that vitamin A intake was inversely associated with lung cancer risk. The effect was most pronounced in the comparisons with the "living" controls and appeared strongest among cigarette smokers. Subjects in the lowest tertile of vitamin A intake had approximately twice the risk of lung cancer as those in the highest. Analyses of an index of carotenoids and of individual food items suggested that plant sources of vitamin A may play a more important role in producing the effect than do animal sources.

Intracranial haemorrhage and use of selective serotonin reuptake inhibitors

PubMed Central

de Abajo, Francisco J; Jick, Hershel; Derby, Laura; Jick, Susan; Schmitz, Stephen

2000-01-01

Aims In the past few years an increasing number of bleeding disorders have been reported in association with the use of selective serotonin reuptake inhibitors (SSRIs), including serious cases of intracranial haemorrhage, raising concerns about the safety of this class of drugs. The present study was performed to test the hypothesis of an increased risk of intracranial haemorrhage associated with the use of SSRIs. Methods We carried out a case-control study nested in a cohort of antidepressants users with the UK-based General Practice Research Database (GPRD) as the primary source of information. The study cohort encompassed subjects aged between 18 and 79 years who received a first-time prescription for any antidepressant from January, 1990 to October, 1997. Patients with presenting conditions or treatments that could be associated with an increased risk of intracranial haemorrhage were excluded from the cohort. Patients were followed-up until the occurrence of an idiopathic intracranial haemorrhage. Up to four controls per case, matched on age, sex, calendar time and practice were randomly selected from the study cohort. We estimated adjusted odds ratios and 95% confidence intervals of intracranial haemorrhage with current use of SSRIs and other antidepressants as compared with nonuse using conditional logistic regression. Results We identified 65 cases of idiopathic intracranial haemorrhage and 254 matched controls. Current exposure to SSRIs was ascertained in 7 cases (10.8%) and 24 controls (9.7%) resulting in an adjusted OR (95%CI) of 0.8 (0.3,2.3). The estimate for ‘other antidepressants’ was 0.7 (0.3,1.6). The effect measures were not modified by gender or age. No effect related to dose or treatment duration was detected. The risk estimates did not change according to the location of bleeding (intracerebral or subarachnoid). Conclusions Our results are not compatible with a major increased risk of intracranial haemorrhage among users of SSRIs or other antidepressants at large. However, smaller but still relevant increased risks cannot be ruled out. PMID:10886117

Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases

PubMed Central

Coupland, Carol; Hippisley-Cox, Julia

2015-01-01

Objective To investigate the association between use of combined oral contraceptives and risk of venous thromboembolism, taking the type of progestogen into account. Design Two nested case-control studies. Setting General practices in the United Kingdom contributing to the Clinical Practice Research Datalink (CPRD; 618 practices) and QResearch primary care database (722 practices). Participants Women aged 15-49 years with a first diagnosis of venous thromboembolism in 2001-13, each matched with up to five controls by age, practice, and calendar year. Main outcome measures Odds ratios for incident venous thromboembolism and use of combined oral contraceptives in the previous year, adjusted for smoking status, alcohol consumption, ethnic group, body mass index, comorbidities, and other contraceptive drugs. Results were combined across the two datasets. Results 5062 cases of venous thromboembolism from CPRD and 5500 from QResearch were analysed. Current exposure to any combined oral contraceptive was associated with an increased risk of venous thromboembolism (adjusted odds ratio 2.97, 95% confidence interval 2.78 to 3.17) compared with no exposure in the previous year. Corresponding risks associated with current exposure to desogestrel (4.28, 3.66 to 5.01), gestodene (3.64, 3.00 to 4.43), drospirenone (4.12, 3.43 to 4.96), and cyproterone (4.27, 3.57 to 5.11) were significantly higher than those for second generation contraceptives levonorgestrel (2.38, 2.18 to 2.59) and norethisterone (2.56, 2.15 to 3.06), and for norgestimate (2.53, 2.17 to 2.96). The number of extra cases of venous thromboembolism per year per 10 000 treated women was lowest for levonorgestrel (6, 95% confidence interval 5 to 7) and norgestimate (6, 5 to 8), and highest for desogestrel (14, 11 to 17) and cyproterone (14, 11 to 17). Conclusions In these population based, case-control studies using two large primary care databases, risks of venous thromboembolism associated with combined oral contraceptives were, with the exception of norgestimate, higher for newer drug preparations than for second generation drugs. PMID:26013557

Excess body iron and the risk of type 2 diabetes mellitus: a nested case-control in the PREDIMED (PREvention with MEDiterranean Diet) study.

PubMed

Arija, Victoria; Fernández-Cao, José C; Basora, Josep; Bulló, Mònica; Aranda, Nuria; Estruch, Ramón; Martínez-González, Miguel A; Salas-Salvadó, Jordi

2014-12-14

A prospective nested case-control study within the PREvention with MEDiterranean Diet (PREDIMED) was conducted to evaluate the relationship between excess body Fe (measured as serum ferritin (SF), soluble transferrin receptor (sTfR) and sTfR:ferritin ratio) and the risk of type 2 diabetes mellitus (T2DM) in a Mediterranean population at a high risk of CVD, without T2DM at the start of the study. The study contained 459 subjects, 153 with incident T2DM (cases) and 306 without incident T2DM (controls). The follow-up period was for 6.0 (interquartile range 3.9-6.5) years. For each incident diabetic subject, two subjects were selected as controls who were matched broadly for age as well as for sex, intervention group and BMI. We observed a relationship between SF values >257 μg/l in males and >139 μg/l in females and the risk of T2DM, following adjustment in the conditional logistic regression model for high-sensitivity C-reactive protein, fasting glucose and other components of the metabolic syndrome (OR 3.62, 95% CI 1.32, 19.95; P= 0.022). We also found an association between low sTfR:ferritin ratio levels and the incidence of T2DM (OR 3.02, 95% CI 1.09, 8.39; P= 0.042), but no association with sTfR (OR 1.29, 95% CI 0.51, 3.23; P= 0.722). Oxidative stress has been hypothesised to contribute to the development of insulin resistance and β-cell dysfunction, the two key events in the clinical development of T2DM. Following adjustment for other risk factors for T2DM, excess body Fe (measured as SF and sTfR:ferritin ratio) was associated with an increased risk of developing T2DM in a Mediterranean population at a high risk of CVD.

A Case–Control Study of Lung Cancer Nested in a Cohort of European Asphalt Workers

PubMed Central

Olsson, Ann; Kromhout, Hans; Agostini, Michela; Hansen, Johnni; Lassen, Christina Funch; Johansen, Christoffer; Kjaerheim, Kristina; Langård, Sverre; Stücker, Isabelle; Ahrens, Wolfgang; Behrens, Thomas; Lindbohm, Marja-Liisa; Heikkilä, Pirjo; Heederik, Dick; Portengen, Lützen; Shaham, Judith; Ferro, Gilles; de Vocht, Frank; Burstyn, Igor; Boffetta, Paolo

2010-01-01

Background We conducted a nested case–control study in a cohort of European asphalt workers in which an increase in lung cancer risk has been reported among workers exposed to airborne bitumen fume, although potential bias and confounding were not fully addressed. Objective We investigated the contribution of exposure to bitumen, other occupational agents, and tobacco smoking to the risk of lung cancer among asphalt workers. Methods Cases were cohort members in Denmark, Finland, France, Germany, the Netherlands, Norway, and Israel who had died of lung cancer between 1980 and the end of follow-up (2002–2005). Controls were individually matched in a 3:1 ratio to cases on year of birth and country. We derived exposure estimates for bitumen fume and condensate, organic vapor, and polycyclic aromatic hydrocarbons, as well as for asbestos, crystalline silica, diesel motor exhaust, and coal tar. Odds ratios (ORs) were calculated for ever-exposure, duration, average exposure, and cumulative exposure after adjusting for tobacco smoking and exposure to coal tar. Results A total of 433 cases and 1,253 controls were included in the analysis. The OR was 1.12 [95% confidence interval (CI), 0.84–1.49] for inhalation exposure to bitumen fume and 1.17 (95% CI, 0.88–1.56) for dermal exposure to bitumen condensate. No significant trend was observed between lung cancer risk and duration, average exposure, or cumulative exposure to bitumen fume or condensate. Conclusions We found no consistent evidence of an association between indicators of either inhalation or dermal exposure to bitumen and lung cancer risk. A sizable proportion of the excess mortality from lung cancer relative to the general population observed in the earlier cohort phase is likely attributable to high tobacco consumption and possibly to coal tar exposure, whereas other occupational agents do not appear to play an important role. PMID:20529766

Human oral microbiome and prospective risk for pancreatic cancer: a population-based nested case-control study.

PubMed

Fan, Xiaozhou; Alekseyenko, Alexander V; Wu, Jing; Peters, Brandilyn A; Jacobs, Eric J; Gapstur, Susan M; Purdue, Mark P; Abnet, Christian C; Stolzenberg-Solomon, Rachael; Miller, George; Ravel, Jacques; Hayes, Richard B; Ahn, Jiyoung

2018-01-01

A history of periodontal disease and the presence of circulating antibodies to selected oral pathogens have been associated with increased risk of pancreatic cancer; however, direct relationships of oral microbes with pancreatic cancer have not been evaluated in prospective studies. We examine the relationship of oral microbiota with subsequent risk of pancreatic cancer in a large nested case-control study. We selected 361 incident adenocarcinoma of pancreas and 371 matched controls from two prospective cohort studies, the American Cancer Society Cancer Prevention Study II and the National Cancer Institute Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. From pre-diagnostic oral wash samples, we characterised the composition of the oral microbiota using bacterial 16S ribosomal RNA (16S rRNA) gene sequencing. The associations between oral microbiota and risk of pancreatic cancer, controlling for the random effect of cohorts and other covariates, were examined using traditional and L1-penalised least absolute shrinkage and selection operator logistic regression. Carriage of oral pathogens, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans , were associated with higher risk of pancreatic cancer (adjusted OR for presence vs absence=1.60 and 95% CI 1.15 to 2.22; OR=2.20 and 95% CI 1.16 to 4.18, respectively). Phylum Fusobacteria and its genus Leptotrichia were associated with decreased pancreatic cancer risk (OR per per cent increase of relative abundance=0.94 and 95% CI 0.89 to 0.99; OR=0.87 and 95% CI 0.79 to 0.95, respectively). Risks related to these phylotypes remained after exclusion of cases that developed within 2 years of sample collection, reducing the likelihood of reverse causation in this prospective study. This study provides supportive evidence that oral microbiota may play a role in the aetiology of pancreatic cancer. 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/.

Increasing maternal percentage body fat in early second trimester: a risk factor for preeclampsia.

PubMed

Wang, Yanxia; Qiu, Jie; Zhou, Min; Wang, Youjie; Du, Yukai

2015-02-01

To determine if maternal percentage body fat (PBF) or fat free mass (FFM) in the early second trimester of pregnancy influenced the development of preeclampsia. A matched nested case-control study was conducted from a cohort study of 1668 women at Gansu provincial maternal and child care hospital from July 2007 to August 2011 in China. Maternal PBF and FFM were assessed by bioelectrical impedance analysis during 12th-16th gestational week. The demographic characteristics were all chart abstracted. After childbirth, 70 cases of preeclampsia were matched by race/age with 140 uncomplicated pregnancies women. Multivariate logistic regression analysis was performed to determine the associated risk factors. Pre-pregnancy body mass index were higher in women who subsequently developed preeclampsia compared with controls (p < 0.001). During 12th-16th gestational week, there were nearly 7-fold increase in the odds of preeclampsia (adjusted OR: 6.84, 95% CI: 4.15-41.60) among women with PBF ≥ 40% versus women with PBF < 40%. But FFM were not at further increased risk of the development of preeclampsia (adjusted OR, 1.02; 95% CI, 0.6-3.6). Maternal PBF but not FFM is a predictor of preeclampsia in the early second trimester. Excessive adipose tissue possibly played an important role in developing of preeclampsia.

Eggs, nests, and nesting behavior of akiapolaau (Drepanidinae)

USGS Publications Warehouse

Banko, P.C.; Williams, J.

1993-01-01

We describe the fifth verified nest and first verified egg of the Akiapolaau (Hemignathus munroi), an endangered Hawaiian honeycreeper. We dispute the validity of Bryan?s (1905a) description of three eggs and two nests of the Akiapolaau. Eggs that he attributed to this species were much smaller than ours, and his nest descriptions did not match the only nest apparently belonging to the Akiapolaau in the B. P. Bishop Museum in Honolulu, where Bryan worked. Twigs and bark were distinctively combined in the nest that we examined. We compare eggs and nests of the Akiapolaau with those of other Hawaiian honeycreepers.

Cohort mortality study of North American industrial sand workers. II. Case-referent analysis of lung cancer and silicosis deaths.

PubMed

Hughes, J M; Weill, H; Rando, R J; Shi, R; McDonald, A D; McDonald, J C

2001-04-01

A cohort mortality study of 2670 men in nine North American industrial sand plants resulted in 83 deaths from lung cancer 20 or more years after hire (standardized mortality ratio 139) and 37 deaths from silicosis (including seven from silico-tuberculosis). The lung cancer excess was unrelated to duration of employment and not found in all plants. The primary aim was to determine whether lung cancer risk among these employees was related to quantitative estimates of crystalline silica exposure, after allowance for cigarette smoking. A secondary aim was to do the same for silicosis mortality, partly as a means of validating the estimated levels of exposure. A nested case-referent study was undertaken with cases matched with up to two controls on plant, age and date of first employment from men who survived the case. Exposures were estimated by linking work histories to a job-exposure matrix, undertaken separately. Cigarette smoking information was obtained from medical records and other sources, blind as to case-control status. Matched statistical analyses were conducted using conditional logistic regression. Odds ratios for silicosis mortality were significantly related to cumulative silica exposures and tended to a relationship with category of average crystalline silica concentration, but inconsistently with length of employment. After accounting for a strong effect of cigarette smoking, odds ratios for lung cancer were related to cumulative crystalline silica exposure and to average silica concentration, but not to length of employment. These findings support a causal relationship between lung cancer and quartz exposure after allowance for cigarette smoking, in the absence of cristobalite or other known occupational carcinogens.

25-hydroxyvitamin D and breast cancer, colorectal cancer, and colorectal adenomas: case-control versus nested case-control studies.

PubMed

Grant, William B

2015-02-01

Existing literature includes concerns regarding reliability of case-control studies of breast cancer incidence with respect to 25-hydroxyvitamin D (25(OH)D) concentrations. For breast cancer, only case-control studies consistently find inverse correlations between 25(OH)D and breast cancer. However, for colorectal cancer, nested case-control studies find significant inverse correlations with respect to 25(OH)D concentrations at baseline for mean follow-up times of 7 years. This is a review of results currently existing in literature. I provide evidence that 25(OH)D concentration values are only useful for short follow-up times for breast cancer since it develops rapidly. To support the robust nature of breast cancer case-control studies, I show that results from 11 studies from seven countries align in a robust power-law fit to the odds ratio versus mean 25(OH)D concentrations. Case-control studies of breast cancer incidence rates provide reliable results. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Neonatal antecedents for cerebral palsy in extremely preterm babies and interaction with maternal factors.

PubMed

Tran, Uyen; Gray, Peter H; O'Callaghan, Michael J

2005-06-01

Preterm delivery is associated with an increased risk of cerebral palsy (CP). The greatest risk is for infants born <28 weeks' gestation. To identify significant neonatal risk factors for CP and explore the interactions between antenatal and neonatal risk factors, among extremely preterm infants of 27 weeks' gestation or less. Nested case control design. Infants born between 1989 and 1996, at 24-27 weeks' gestation, were evaluated: 30 with CP at 2 years corrected age and 120 control infants matched for gestation age. Neonatal variables were compared using matched analyses with the interaction between antenatal and neonatal factors being examined using logistic regression analyses. Risk factors for CP on matched analyses included patent ductus arteriosus requiring surgical ligation, peri-intraventricular haemorrhage, moderate to severe ventricular dilatation, periventricular leukomalacia (PVL) and need for home oxygen. Independent neonatal predictors were ventricular dilatation (OR 7.3; 95% CI 1.6, 32.3), PVL (OR 29.8; 95% CI 5.6, 159.1) and home oxygen use (OR 3.4; 95% CI 1.2, 9.4). No interaction terms in the logistic models were significant between the previously identified pregnancy risk factors of absence of antenatal steroids and intrauterine growth restriction and the neonatal risk factors. PVL is the most powerful independent predictor of CP in extremely preterm infants of 27 weeks' gestation or less and appears to be uninfluenced by antenatal factors.

Risk factors for tuberculosis among health care workers in South India: a nested case-control study.

PubMed

Mathew, Anoop; David, Thambu; Thomas, Kurien; Kuruvilla, P J; Balaji, V; Jesudason, Mary V; Samuel, Prasanna

2013-01-01

The epidemiology of tuberculosis (TB) among health care workers (HCWs) in India remains under-researched. This study is a nested case-control design assessing the risk factors for acquiring TB among HCWs in India. It is a nested case-control study conducted at a tertiary teaching hospital in India. Cases (n = 101) were HCWs with active TB. Controls (n = 101) were HCWs who did not have TB, randomly selected from the 6,003 subjects employed at the facility. Cases and controls were compared with respect to clinical and demographic variables. The cases and controls were of similar age. Logistic regression analysis showed that body mass index (BMI) <19 kg/m(2) (odds ratio [OR]: 2.96, 95% confidence interval [CI]: 1.49-5.87), having frequent contact with patients (OR: 2.83, 95% CI: 1.47-5.45) and being employed in medical wards (OR: 12.37, 95% CI: 1.38-110.17) or microbiology laboratories (OR: 5.65, 95% CI: 1.74-18.36) were independently associated with increased risk of acquiring TB. HCWs with frequent patient contact and those with BMI <19 kg/m(2) were at high risk of acquiring active TB. Nosocomial transmission of TB was pronounced in locations, such as medical wards and microbiology laboratories. Surveillance of high-risk HCWs and appropriate infrastructure modifications may be important to prevent interpersonal TB transmission in health care facilities. Copyright © 2013 Elsevier Inc. All rights reserved.

Endogenous steroid hormone levels in early pregnancy and risk of testicular cancer in the offspring: a nested case-referent study.

PubMed

Holl, Katsiaryna; Lundin, Eva; Surcel, Heljä-Marja; Grankvist, Kjell; Koskela, Pentti; Dillner, Joakim; Hallmans, Göran; Wadell, Göran; Olafsdottir, Gudridur H; Ogmundsdottir, Helga M; Pukkala, Eero; Lehtinen, Matti; Stattin, Pär; Lukanova, Annekatrin

2009-06-15

According to the leading hypothesis on testicular cancer (TC) etiology exposure to a specific pattern of steroid hormones in utero, in particular, to high levels of estrogens and low levels of androgens is the major determinant of TC risk in the offspring. We performed a case-referent study nested within Finnish, Swedish and Icelandic maternity cohorts exploiting early pregnancy serum samples to evaluate the role of maternal endogenous steroid hormones with regard to the risk of TC. TC cases and referents were aged between 0 and 25 years. For each case-index mother pair, three or four matched referent-referent mother pairs were identified using national population registries. First trimester or early second trimester sera were retrieved from the index mothers of 73 TC cases and 286 matched referent mothers, and were tested for dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, estradiol, estrone, and sex hormone binding globulin (SHBG). Offspring of mothers with high DHEAS levels had a significantly decreased risk of TC (OR for highest vs. lowest DHEAS quartile, 0.18 (95% CI 0.06-0.58). In contrast, offspring of mothers with high androstenedione levels had an increased risk of TC (OR 4.1; 95% CI 1.2-12.0). High maternal total estradiol level also tended to be associated with an increased risk of TC in the offspring (OR 32; 95% CI 0.98-1,090). We report the first direct evidence that interplay of maternal steroid hormones in the early pregnancy is important in the etiology of TC in the offspring. Copyright 2008 UICC.

MicroRNA expression in benign breast tissue and risk of subsequent invasive breast cancer.

PubMed

Rohan, Thomas; Ye, Kenny; Wang, Yihong; Glass, Andrew G; Ginsberg, Mindy; Loudig, Olivier

2018-01-01

MicroRNAs are endogenous, small non-coding RNAs that control gene expression by directing their target mRNAs for degradation and/or posttranscriptional repression. Abnormal expression of microRNAs is thought to contribute to the development and progression of cancer. A history of benign breast disease (BBD) is associated with increased risk of subsequent breast cancer. However, no large-scale study has examined the association between microRNA expression in BBD tissue and risk of subsequent invasive breast cancer (IBC). We conducted discovery and validation case-control studies nested in a cohort of 15,395 women diagnosed with BBD in a large health plan between 1971 and 2006 and followed to mid-2015. Cases were women with BBD who developed subsequent IBC; controls were matched 1:1 to cases on age, age at diagnosis of BBD, and duration of plan membership. The discovery stage (316 case-control pairs) entailed use of the Illumina MicroRNA Expression Profiling Assay (in duplicate) to identify breast cancer-associated microRNAs. MicroRNAs identified at this stage were ranked by the strength of the correlation between Illumina array and quantitative PCR results for 15 case-control pairs. The top ranked 14 microRNAs entered the validation stage (165 case-control pairs) which was conducted using quantitative PCR (in triplicate). In both stages, linear regression was used to evaluate the association between the mean expression level of each microRNA (response variable) and case-control status (independent variable); paired t-tests were also used in the validation stage. None of the 14 validation stage microRNAs was associated with breast cancer risk. The results of this study suggest that microRNA expression in benign breast tissue does not influence the risk of subsequent IBC.

MicroRNA expression in benign breast tissue and risk of subsequent invasive breast cancer

PubMed Central

Ye, Kenny; Wang, Yihong; Ginsberg, Mindy; Loudig, Olivier

2018-01-01

MicroRNAs are endogenous, small non-coding RNAs that control gene expression by directing their target mRNAs for degradation and/or posttranscriptional repression. Abnormal expression of microRNAs is thought to contribute to the development and progression of cancer. A history of benign breast disease (BBD) is associated with increased risk of subsequent breast cancer. However, no large-scale study has examined the association between microRNA expression in BBD tissue and risk of subsequent invasive breast cancer (IBC). We conducted discovery and validation case-control studies nested in a cohort of 15,395 women diagnosed with BBD in a large health plan between 1971 and 2006 and followed to mid-2015. Cases were women with BBD who developed subsequent IBC; controls were matched 1:1 to cases on age, age at diagnosis of BBD, and duration of plan membership. The discovery stage (316 case-control pairs) entailed use of the Illumina MicroRNA Expression Profiling Assay (in duplicate) to identify breast cancer-associated microRNAs. MicroRNAs identified at this stage were ranked by the strength of the correlation between Illumina array and quantitative PCR results for 15 case-control pairs. The top ranked 14 microRNAs entered the validation stage (165 case-control pairs) which was conducted using quantitative PCR (in triplicate). In both stages, linear regression was used to evaluate the association between the mean expression level of each microRNA (response variable) and case-control status (independent variable); paired t-tests were also used in the validation stage. None of the 14 validation stage microRNAs was associated with breast cancer risk. The results of this study suggest that microRNA expression in benign breast tissue does not influence the risk of subsequent IBC. PMID:29432432

Direct medical costs of constipation in children over 15 years: a population-based birth cohort

PubMed Central

Choung, Rok Seon; Shah, Nilay D.; Chitkara, Denesh; Branda, Megan E.; Van Tilburg, Miranda A.; Whitehead, William E.; Katusic, Slavica K.; Locke, G. Richard; Talley, Nicholas J.

2011-01-01

Background Although direct medical costs for constipation-related medical visits are thought to be high, to date there have been no studies examining if longitudinal resource utilization is persistently elevated in children with constipation. Our aim was to estimate the incremental direct medical costs and types of health care utilization associated with constipation from childhood to early adulthood. Methods A nested case-control study was conducted to evaluate the incremental costs associated with constipation. The original sample consisted of 5,718 children in a population-based birth cohort who were born during 1976–1982 in Rochester, MN. The cases included individuals who presented to medical facilities with constipation. The controls were matched and randomly selected among all non-cases in the sample. Direct medical costs for cases and controls were collected from the time subjects were between 5–18 years of age or until the subject emigrated from the community. Results We identified 250 cases with a diagnosis of constipation in the birth cohort. While the mean inpatient costs for cases were $9994 (95% CI=2538, 37201) compared to $2391 (95% CI=923, 7452) for controls (p=0.22) over the time period, the mean outpatient costs for cases were $13927 (95% CI=11325, 16525) compared to $3448 (95% CI=3771, 4621) for controls (p<0.001) over the same time period. The mean annual number emergency department visits for cases were 0.66 (95% CI=0.62, 0.70) compared to 0.34 (95% CI=0.32, 0.35) for controls (p<0.0001). Conclusion Individuals with constipation have higher medical care utilization. Outpatient costs and ER utilization were significantly greater for individuals with constipation from childhood to early adulthood. PMID:20890220

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

PubMed

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

2018-05-05

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

New use of low-dose aspirin and risk of colorectal cancer by stage at diagnosis: a nested case-control study in UK general practice.

PubMed

García Rodríguez, Luis A; Soriano-Gabarró, Montse; Bromley, Susan; Lanas, Angel; Cea Soriano, Lucía

2017-09-07

Evidence from clinical trial populations suggests low-dose aspirin reduces the risk of colorectal cancer (CRC). Part of this reduction in risk might be due to protection against metastatic disease. We investigated the risk of CRC among new-users of low-dose aspirin (75-300 mg), including risk by stage at diagnosis. Using The Health Improvement Network, we conducted a cohort study with nested case-control analysis. Two cohorts (N = 170,336 each) aged 40-89 years from 2000 to 2009 and free of cancer were identified: i) new-users of low-dose aspirin, ii) non-users of low-dose aspirin, at start of follow-up, matched by age, sex and previous primary care practitioner visits. Patients were followed for up to 12 years to identify incident CRC. 10,000 frequency-matched controls were selected by incidence density sampling where the odds ratio is an unbiased estimator of the incidence rate ratio (RR). RRs with 95% confidence intervals were calculated. Low-dose aspirin use was classified 'as-treated' independent from baseline exposure status to account for changes in exposure during follow-up. Current users of low-dose aspirin (use on the index date or in the previous 90 days) had a significantly reduced risk of CRC, RR 0.66 (95% CI 0.60-0.74). The reduction in risk was apparent across all age groups, and was unrelated to dose, indication, gender, CRC location or case-fatality status. Reduced risks occurred throughout treatment duration and with all low-dose aspirin doses. RRs by aspirin indication were 0.71 (0·63-0·79) and 0.60 (0.53-0.68) for primary and secondary cardiovascular protection, respectively. Among cases with staging information (n = 1421), RRs for current use of low-dose aspirin were 0.94 (0.66-1.33) for Dukes Stage A CRC, 0.54 (0.42-0.68) for Dukes B, 0.71 (0.56-0.91) for Dukes C, and 0.60 (0.48-0.74) for Dukes D. After 5 years' therapy, the RR for Dukes Stage A CRC was 0.53 (0.24-1.19). Patients starting low-dose aspirin therapy have a reduced risk of Stages B-D CRC, suggesting a role for low-dose aspirin in the progression of established CRC; a substantial reduction in the risk of Dukes A CRC may occur after 5 years' therapy.

Cancer complicating systemic lupus erythematosus – a dichotomy emerging from a nested case-control study

PubMed Central

Kenu, E; Isenberg, DA

2013-01-01

Objectives We determined whether any individual cancers are increased or decreased in a cohort of 595 patients with systemic lupus erythematosus (SLE) followed for up to 32 years at the University College London Hospitals Lupus Clinic, looking for any associated clinical or serological factors and the prognosis after cancer diagnosis. Methods We undertook a careful retrospective review of the medical records and identified all individuals diagnosed with cancer. For controls, we selected three other patients in the cohort who had not developed cancer, carefully matched for age, sex, ethnicity and disease duration, to determine if any obvious differences emerged in a nested case-control design. Results Thirty-three patients developed cancer after being diagnosed with SLE. There was a statistically insignificant small increase in overall cancer risk, standardized incidence ratios (SIRs) 1.05 (95% CI 0.52–1.58) and increased SIRs for cervical, prostate, anal and pancreatic cancers and reduction in breast cancer SIRs. Haematological and musculoskeletal manifestations, anticardiolipin and antithyroid globulin antibodies were found to be positively associated with cancer risk in multivariate analysis. There was no drug, dose or duration was associated with cancer risk. There was a reduction in survival with a cancer fatality rate of 84.2% (p < 0.0001). Conclusion We found a very small but statistically insignificant increased cancer risk with reduction in survival. Whereas some cancers appear to be more common in SLE, notably prostate and cervical cancer, others, particularly breast cancer, are less frequent. Multiple clinical and serological factors are involved in the increased risk of malignancy in SLE. No drug dose or duration effect was identified. PMID:23857987

Parental age and risk of genetic syndromes predisposing to nervous system tumors: nested case–control study

PubMed Central

Adel Fahmideh, Maral; Tettamanti, Giorgio; Lavebratt, Catharina; Talbäck, Mats; Mathiesen, Tiit; Lannering, Birgitta; Johnson, Kimberly J; Feychting, Maria

2018-01-01

Purpose Phacomatoses are genetic syndromes that are associated with increased risk of developing nervous system tumors. Phacomatoses are usually inherited, but many develop de novo, with unknown etiology. In this population-based study, we investigated the effect of parental age on the risk of phacomatoses in offspring. Patients and methods The study was a population-based nested case–control study. All individuals born and residing in Sweden between January 1960 and December 2010 were eligible for inclusion. Using the Patient Register, 4625 phacomatosis cases were identified and further classified as familial or nonfamilial. Ten matched controls per case were randomly selected from the eligible population. Data were analyzed using conditional logistic regression. Analyses were conducted for neurofibromatosis alone (n=2089) and other phacomatoses combined (n=2536). Results Compared with offspring of fathers aged 25–29 years, increased risk estimates of nonfamilial neurofibromatosis were found for offspring of fathers aged 35–39 years (odds ratio [OR]=1.43 [95% CI 1.16–1.74]) and ≥40 years (OR =1.74 [95% CI 1.38–2.19]). For other nonfamilial phacomatoses, the risk estimate for offspring of fathers aged ≥40 years was OR =1.23 (95% CI 1.01–1.50). Paternal age was not associated with familial phacomatoses, and no consistent association was observed with maternal age. Conclusion The findings show a consistent increase in risk of de novo occurrence of phacomatoses predisposing to nervous system tumors in offspring with increasing paternal age, most pronounced for neurofibromatosis, while maternal age did not seem to influence the risk. These findings suggest an increasing rate of new mutations in the NF1 and NF2 genes in spermatozoa of older fathers.

Anthropometric predictors of gestational hypertensive disorders in a remote aboriginal community: a nested case-control study.

PubMed

Sina, Maryam; Hoy, Wendy; Wang, Zhiqiang

2014-03-05

Australian Aboriginal women tend to have body shape and pregnancy risk profiles different from other Australian women. This study aims to examine the associations of anthropometric indices with gestational hypertensive disorders (GHD), and to determine the index that can best predict the risk of this condition occurring during pregnancy. This is a nested case-control study. Baseline body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were measured as part of a broader health screening program between 1992 and 1995 in a remote Aboriginal community. All subsequent pregnancies among the original participants were identified during 20 year follow-up period through hospital records (up to May 2012). Twenty eight women were diagnosed as having GHD, each of whom were individually matched by age at baseline with five women who were hospitalised for other pregnancy-related conditions and were free from GHD (n = 140). The associations of the baseline anthropometric measurements with GHD were assessed using conditional logistic regression. The best predictor of GHD was WC (OR = 1.8; (95% CI, 1.1-2.9) for one standard deviation increase in WC), followed by BMI with the corresponding OR = 1.7 (95% CI, 1.1- 2.6). Other measurements, HC, WHR, and WHtR, were also positively associated with GHD, but those associations were not statistically significant. WC and BMI prior to pregnancy are anthropometric predictors of GHD in Aboriginal women, and WC is the best predictor. These findings imply the importance of early weight control in preventing GHD in Aboriginal women.

Risk factors for CKD in persons with kidney stones: a case-control study in Olmsted County, Minnesota.

PubMed

Saucier, Nathan A; Sinha, Mukesh K; Liang, Kelly V; Krambeck, Amy E; Weaver, Amy L; Bergstralh, Eric J; Li, Xujian; Rule, Andrew D; Lieske, John C

2010-01-01

Kidney stones are associated with increased risk of chronic kidney disease (CKD); however, risk factors in the general community are poorly defined. A nested case-control study was performed in residents of Olmsted County, MN, who presented with a kidney stone at the Mayo Clinic in 1980-1994 to contrast patients with kidney stones who developed CKD with a group that did not. Participants were selected from the Rochester Epidemiology Project, an electronic linkage system among health care providers in Olmsted County, MN. Cases were identified by diagnostic code for CKD and confirmed to have an estimated glomerular filtration rate < 60 mL/min/1.73 m(2). Controls were matched 2:1 to cases for age, sex, date of first kidney stone, and length of medical record. Charts were abstracted to characterize stone disease, hypertension, diabetes, obesity, tobacco use, ileal conduit, symptomatic stones, type and number of stones, urinary tract infections, number and type of surgical procedures, and medical therapy. Kidney stone patients with CKD were compared with matched stone patients without CKD. There were 53 cases and 106 controls with a mean age of 57 years at first stone event and 59% men. In kidney stone patients, cases with CKD were significantly more likely (P < 0.05) than controls to have had a history of diabetes (41.5% vs 17.0%), hypertension (71.7% vs 49.1%), frequent urinary tract infections (22.6% vs 6.6%), struvite stones (7.5% vs 0%), and allopurinol use (32.1% vs 4.7%) based on univariate analysis. Potential limitations include limited statistical power to detect associations, incomplete data from 24-hour urine studies, and that stone composition was not always available. As in the general population, hypertension and diabetes are associated with increased risk of CKD in patients with kidney stones. However, other unique predictors were identified in patients with kidney stones that increased the possibility of CKD. Further studies are warranted to elucidate the nature of these associations. Copyright 2009 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Unconditional or Conditional Logistic Regression Model for Age-Matched Case–Control Data?

PubMed Central

Kuo, Chia-Ling; Duan, Yinghui; Grady, James

2018-01-01

Matching on demographic variables is commonly used in case–control studies to adjust for confounding at the design stage. There is a presumption that matched data need to be analyzed by matched methods. Conditional logistic regression has become a standard for matched case–control data to tackle the sparse data problem. The sparse data problem, however, may not be a concern for loose-matching data when the matching between cases and controls is not unique, and one case can be matched to other controls without substantially changing the association. Data matched on a few demographic variables are clearly loose-matching data, and we hypothesize that unconditional logistic regression is a proper method to perform. To address the hypothesis, we compare unconditional and conditional logistic regression models by precision in estimates and hypothesis testing using simulated matched case–control data. Our results support our hypothesis; however, the unconditional model is not as robust as the conditional model to the matching distortion that the matching process not only makes cases and controls similar for matching variables but also for the exposure status. When the study design involves other complex features or the computational burden is high, matching in loose-matching data can be ignored for negligible loss in testing and estimation if the distributions of matching variables are not extremely different between cases and controls. PMID:29552553

Central Nervous System Medication Burden and Serious Falls in Older Nursing Home Residents

PubMed Central

Hanlon, Joseph T.; Zhao, Xinhua; Naples, Jennifer G.; Aspinall, Sherrie L.; Perera, Subashan; Nace, David A.; Castle, Nicholas G.; Greenspan, Susan L.; Thorpe, Carolyn T.

2016-01-01

Objectives To examine the association between CNS medication burden and serious falls in those with a recent fall history. Design Nested-case control study; cases matched to four controls by age, gender, and date. Setting US nursing homes Participants 5,556 residents age ≥ 65 with a recent fall history admitted to a nursing home between 1/1–9/30/2010 and followed until discharge, death, or 12/31/2010. Measurements Outcome was serious falls as per Medicare Part A and B ICD/CPT codes. CNS burden, from Medicare Part D data, was calculated by dividing the daily dose of each CNS agent (i.e., specific antidepressants, antiepileptic, antipsychotic, benzodiazepine and opioid receptor agonists) received during the six days prior to the index (outcome) date by the minimum effective geriatric daily dose and summing the results across medications. Results There were 367 cases and 1468 matched controls. Those taking 3+ CNS standardized daily doses were more likely to have a serious fall than those not taking any CNS medications (Adjusted Odds Ratio 1.83; 95% confidence interval 1.35–2.48). There was no significant difference in fall risk for residents taking >0 to <3 CNS standardized daily doses compared to residents taking no CNS medications (Adjusted Odds Ratio 0.85; 95% CI 0.63–1.15). Conclusion CNS medication burden, approximately 3+ standardized daily doses, was associated with an increased risk of serious falls in nursing home residents with recent fall. Clinicians should be vigilant for opportunities to discontinue or decrease the doses of individual CNS medications and/or consider non-pharmacological alternatives. Such interventions that reduce use of CNS medications in nursing homes could reduce fall rates but further research is needed to confirm this. PMID:28152179

Correlation between cognitive impairment during the acute phase of first cerebral infarction and development of long-term pseudobulbar affect.

PubMed

Wang, Yuan; Wang, Yuliang; Ma, Wenbin; Lu, Shujun; Chen, Jinbo; Cao, Lili

2018-01-01

The relationship between cognitive impairment during the acute phase of first cerebral infarction and the development of long-term pseudobulbar affect (PBA) has not been elucidated. Therefore, in this study, we aimed to determine if cognitive impairment during the acute phase of cerebral infarction will increase the risk of long-term post-infarction PBA. This was a nested case-control study using a prospective approach. A consecutive multicenter matched 1:1 case-control study of cognitive impairment cases following acute cerebral infarction (N=26) with 26 sex-, education years-, and age-matched controls. Univariate and multivariate conditional logistic regression analyses were performed to study the clinical features and changes in cognitive domain as well as the risk factors for PBA. Long-term PBA was independently predicted by low Montreal cognitive assessment (MoCA) scores at baseline. Multivariable regression models showed that post-infarction low MoCA scores remained independent predictors of long-term PBA (odds ratio [OR]=0.72; 95% confidence interval [CI]=0.54-0.95; P =0.018). Among all cognitive disorders, digit span test (DST) scores (OR=0.39; 95% CI=0.16-0.91, P =0.030), StroopC time (OR=1.15; 95% CI=1.01-1.31; P =0.037), and clock-drawing task (CDT) scores (OR=0.62; 95% CI=0.42-0.90; P =0.013) were found to be the independent risk factors for PBA. Cognitive impairment during the acute phase of cerebral infarction increased the risk of cerebral infarction-induced long-term PBA. Development of PBA was closely associated with executive function, attention, and visuospatial disorder.

Circulating cadmium concentration and risk of aortic aneurysms: A nested case-control study within the Malmö Diet and Cancer cohort.

PubMed

Fagerberg, Björn; Borné, Yan; Sallsten, Gerd; Smith, J Gustav; Acosta, Stefan; Persson, Margaretha; Melander, Olle; Forsgard, Niklas; Gottsäter, Anders; Hedblad, Bo; Barregard, Lars; Engström, Gunnar

2017-06-01

Diet and smoking expose the general population to cadmium (Cd), which is a toxic metal that accumulates in the arterial wall. In experimental studies, Cd causes reductions in proliferation of smooth muscle cells and cellular synthesis of procollagen. The aim of this study was to examine whether blood Cd levels, a valid measure of Cd exposure, are associated with increased risk of abdominal aortic aneurysm (AAA). All middle-aged men and women enrolled in the Malmö Diet and Cancer study (n = 30 447) were followed from the baseline examination in 1991-1996 through 2009. A total of 297 cases with AAA and two randomly selected control subjects for each case, matched for age and sex, were included. Blood Cd was analysed by inductively coupled plasma mass spectrometry. Diagnoses of AAA, thoracic aortic aneurysm and aortic dissection were obtained from registers. Increased blood Cd was associated with increased risk of incident AAA after adjustment for smoking and other established risk factors for AAA. The highest tertile of blood Cd concentrations had a rate ratio of 2.5 (95% confidence interval 1.3, 5.0) for incident AAA. Concentration of blood Cd (log transformed) was not associated with AAA in never-smokers (n = 24). Blood Cd levels corresponding to the upper tertile of the distribution in the age- and sex-matched control group were associated with a 2.5-fold increase in rate ratio for incident AAA. This relationship was not found in the small group of never-smokers. Copyright © 2017. Published by Elsevier B.V.

Optimal case-control matching in practice.

PubMed

Cologne, J B; Shibata, Y

1995-05-01

We illustrate modern matching techniques and discuss practical issues in defining the closeness of matching for retrospective case-control designs (in which the pool of subjects already exists when the study commences). We empirically compare matching on a balancing score, analogous to the propensity score for treated/control matching, with matching on a weighted distance measure. Although both methods in principle produce balance between cases and controls in the marginal distributions of the matching covariates, the weighted distance measure provides better balance in practice because the balancing score can be poorly estimated. We emphasize the use of optimal matching based on efficient network algorithms. An illustration is based on the design of a case-control study of hepatitis B virus infection as a possible confounder and/or effect modifier of radiation-related primary liver cancer in atomic bomb survivors.

Circulating 25-Hydroxyvitamin D and Risk of Kidney Cancer

PubMed Central

Gallicchio, Lisa; Moore, Lee E.; Stevens, Victoria L.; Ahn, Jiyoung; Albanes, Demetrius; Hartmuller, Virginia; Setiawan, V. Wendy; Helzlsouer, Kathy J.; Yang, Gong; Xiang, Yong-Bing; Shu, Xiao-Ou; Snyder, Kirk; Weinstein, Stephanie J.; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Cai, Qiuyin; Campbell, David S.; Chen, Yu; Chow, Wong-Ho; Horst, Ronald L.; Kolonel, Laurence N.; McCullough, Marjorie L.; Purdue, Mark P.; Koenig, Karen L.

2010-01-01

Although the kidney is a major organ for vitamin D metabolism, activity, and calcium-related homeostasis, little is known about whether this nutrient plays a role in the development or the inhibition of kidney cancer. To address this gap in knowledge, the authors examined the association between circulating 25-hydroxyvitamin D (25(OH)D) and kidney cancer within a large, nested case-control study developed as part of the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. Concentrations of 25(OH)D were measured from 775 kidney cancer cases and 775 age-, sex-, race-, and season-matched controls from 8 prospective cohort studies. Overall, neither low nor high concentrations of circulating 25(OH)D were significantly associated with kidney cancer risk. Although the data showed a statistically significant decreased risk for females (odds ratio = 0.31, 95% confidence interval: 0.12, 0.85) with 25(OH)D concentrations of ≥75 nmol/L, the linear trend was not statistically significant and the number of cases in this category was small (n = 14). The findings from this consortium-based study do not support the hypothesis that vitamin D is inversely associated with the risk of kidney cancer overall or with renal cell carcinoma specifically. PMID:20562187

Serological Documentation of Maternal Influenza Exposure and Bipolar Disorder in Adult Offspring

PubMed Central

Canetta, Sarah E.; Bao, Yuanyuan; Co, Mary Dawn T.; Ennis, Francis A.; Cruz, John; Terajima, Masanori; Shen, Ling; Kellendonk, Christoph; Schaefer, Catherine A.; Brown, Alan S.

2014-01-01

Objective The goal of the present study was to evaluate whether serologically confirmed maternal exposure to influenza is associated with an increased risk of bipolar disorder in the offspring and with subtypes of bipolar disorder, with and without psychotic features. Method The study utilized a nested case-control design in the Child Health and Development Study birth cohort. Eighty-five cases of bipolar disorder were identified following extensive ascertainment and diagnostic assessment and matched to 170 controls in the analysis. Serological documentation of maternal exposure to influenza was determined using the hemagglutination inhibition assay. Results There was no association between serologically documented maternal exposure to influenza and bipolar disorder in offspring. However, maternal serologic influenza exposure was related to a significant, fivefold increased risk of bipolar disorder with psychotic features. Conclusions These results suggest that maternal influenza exposure may increase the risk for the offspring developing bipolar disorder with psychotic features. Taken together with earlier associations between prenatal influenza exposure and schizophrenia, this may suggest that prenatal influenza is a risk factor for psychosis, rather than for a specific psychotic disorder diagnosis. PMID:24480930

Chemical exposures and respiratory cancer among Finnish woodworkers.

PubMed Central

Kauppinen, T P; Partanen, T J; Hernberg, S G; Nickels, J I; Luukkonen, R A; Hakulinen, T R; Pukkala, E I

1993-01-01

A case-control study of respiratory cancer, nested within a cohort of male woodworkers, was updated in Finland. The update extended the initial follow up of 3805 workers from 19 plants to 7307 workers from 35 plants. Each case of respiratory cancer (n = 136) diagnosed between 1957 and 1982 within the cohort was matched by year of birth with three controls (n = 408) from the cohort. Chemical exposures were assessed for the cases and the controls by a plant and period specific job exposure matrix. An excess of respiratory cancer was associated with phenol. Concomitant exposures to several other agents occurred as well, however, and no exposure-response relation for phenol was seen. An excess risk and an increasing exposure-response relation were found for engine exhaust from petrol and diesel driven factory trucks. The excess risk associated with pesticides was lower than in our previous study, an indication of qualitative and quantitative differences in exposure between the initial and augmented cohorts. Slightly increased risks were found for terpenes and mould spores, which may be due to chance although the contribution of occupational exposure cannot be ruled out. Exposure to wood dust, mainly from pine, spruce and birch, at a level of about 1 mg/m3, was not associated with lung cancer, upper respiratory cancer, or adenocarcinoma of the lung. PMID:8435346

Direct medical costs of constipation from childhood to early adulthood: a population-based birth cohort study.

PubMed

Choung, Rok Seon; Shah, Nilay D; Chitkara, Denesh; Branda, Megan E; Van Tilburg, Miranda A; Whitehead, William E; Katusic, Slavica K; Locke, G Richard; Talley, Nicholas J

2011-01-01

Although direct medical costs for constipation-related medical visits are thought to be high, to date there have been no studies examining whether longitudinal resource use is persistently elevated in children with constipation. Our aim was to estimate the incremental direct medical costs and types of health care use associated with constipation from childhood to early adulthood. A nested case-control study was conducted to evaluate the incremental costs associated with constipation. The original sample consisted of 5718 children in a population-based birth cohort who were born during 1976 to 1982 in Rochester, MN. The cases included individuals who presented to medical facilities with constipation. The controls were matched and randomly selected among all noncases in the sample. Direct medical costs for cases and controls were collected from the time subjects were between 5 and 18 years of age or until the subject emigrated from the community. We identified 250 cases with a diagnosis of constipation in the birth cohort. Although the mean inpatient costs for cases were $9994 (95% Confidence interval [CI] 2538-37,201) compared with $2391 (95% CI 923-7452) for controls (P = 0.22) during the time period, the mean outpatient costs for cases were $13,927 (95% CI 11,325-16,525) compared with $3448 (95% CI 3771-4621) for controls (P < 0.001) during the same time period. The mean annual number of emergency department visits for cases was 0.66 (95% CI 0.62-0.70) compared with 0.34 (95% CI 0.32-0.35) for controls (P < 0.0001). Individuals with constipation have higher medical care use. Outpatient costs and emergency department use were significantly greater for individuals with constipation from childhood to early adulthood.

Acrylamide Hemoglobin Adduct Levels and Ovarian Cancer Risk: a nested case-control study

PubMed Central

Xie, Jing; Terry, Kathryn L.; Poole, Elizabeth M.; Wilson, Kathryn M.; Rosner, Bernard A.; Willett, Walter C.; Vesper, Hubert W.; Tworoger, Shelley S.

2013-01-01

Background Acrylamide is a probable human carcinogen formed during cooking of starchy foods. Two large prospective cohort studies of dietary acrylamide intake and ovarian cancer risk observed a positive association, although two other studies reported no association. Methods We measured acrylamide exposure using red blood cell acrylamide and glycidamide hemoglobin adducts among women in two large prospective cohorts: the Nurses’ Health Study and Nurses’ Health Study II. Between blood collection and 2010, we identified 263 incident cases of epithelial ovarian cancer, matching two controls per case. We used logistic regression models to examine the association between acrylamide exposure and ovarian cancer risk, adjusting for matching factors, family history of ovarian cancer, tubal ligation, oral contraceptive use, body mass index (BMI), parity, alcohol intake, smoking, physical activity, and caffeine intake. Results The multivariate-adjusted relative risk (RR) of ovarian cancer comparing the highest versus lowest tertile of total acrylamide adducts was 0.79 (95% CI: 0.50–1.24, P trend = 0.08). The comparable RR of ovarian cancer among non-smokers at blood draw was 0.85 (95% CI: 0.57–1.27, P trend =0.14). The association did not differ by tumor histology (serous invasive versus not), P for heterogeneity=0.41. Individual adduct types (acrylamide or glycidamide) were not associated with risk. Conclusions We observed no evidence that acrylamide exposure as measured by adducts to hemoglobin is associated with an increased risk of ovarian cancer. Impact Our finding indicates that acrylamide intake may not increase risk of ovarian cancer. PMID:23417989

Egg size matching by an intraspecific brood parasite

USGS Publications Warehouse

Lemons, Patrick R.; Sedinger, James S.

2011-01-01

Avian brood parasitism provides an ideal system with which to understand animal recognition and its affect on fitness. This phenomenon of laying eggs in the nests of other individuals has classically been framed from the perspective of interspecific brood parasitism and host recognition of parasitic eggs. Few examples exist of strategies adopted by intraspecific brood parasites to maximize success of parasitic eggs. Intraspecific brood parasitism within precocial birds can be a risky strategy in that hatch synchrony is essential to reproductive success. Given that egg size is positively correlated with incubation time, parasitic birds would benefit by recognizing and selecting hosts with a similar egg size. Intraspecific brood parasitism is an alternative reproductive strategy in black brant (Branta bernicla nigricans), a colonial nesting goose with precocial young. Based on a randomization test, parasitic eggs in this study differed less in size from eggs in their host's nests than did random eggs placed in random nests. Parasitic eggs were remarkably similar in size to hosts’ eggs, differing by <2% of volume on average from host eggs, whereas randomly paired eggs in random nests differed by nearly 8%. The precision with which parasitic brant match the egg size of hosts in our study supports our hypothesis that brant match egg size of hosts, thereby maximizing hatching success of their parasitic eggs.

Animal product consumption and subsequent fatal breast cancer risk among Seventh-day Adventists.

PubMed

Mills, P K; Annegers, J F; Phillips, R L

1988-03-01

Seventh-day Adventist women experience lower mortality rates from breast cancer than other white females in the United States. To evaluate the role of diet in relation to breast cancer within this unique population (more than one-half of all Adventist women are lacto-ovo-vegetarians), a nested case-control study was conducted including 142 cases of fatal breast cancer and 852 matched controls among California Seventh-day Adventist women in 1960-1980. No significant relations between the consumption of animal products (meat, milk, cheese, and eggs) and breast cancer were evident. Odds ratios of 1.00, 1.22, and 1.03 were observed for meat consumption categories of none or occasional, 1-3 days/week, and 4+ days/week, respectively. However, among those women who experienced a relatively early age at natural menopause (less than or equal to 48 years), a suggestive though nonsignificant, positive association between meat consumption and risk was noted. These relations remained unchanged after simultaneously controlling for the effects of other covariates (menstrual characteristics and obesity) via conditional logistic regression analysis. Risk was not related to age at first exposure to the vegetarian lifestyle nor to duration of exposure to the vegetarian lifestyle.

Risk factors for breast cancer in a cohort of mammographic screening program: a nested case-control study within the FRiCaM study.

PubMed

Bravi, Francesca; Decarli, Adriano; Russo, Antonio Giampiero

2018-05-01

Breast cancer is the most common cancer diagnosis and the leading cause of cancer death among women in the world, and differences across populations indicate a role of hormonal, reproductive and lifestyle factors. This study is based on a cohort of 78,050 women invited to undergo a mammogram by Local Health Authority of Milan, between 2003 and 2007. We carried out a nested case-control study including all the 3303 incident breast cancer cases diagnosed up to 2015, and 9909 controls matched by age and year of enrollment. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using logistic regression models. The ORs were 0.88 (95% CI: 0.78-0.98) for an age at menarche ≥14 years and 1.39 (95% CI: 1.07-1.81) for an age of 30 years or older at first pregnancy. Body mass index (BMI) was positively associated with breast cancer risk in women older than 50 years (OR = 1.89, 95% CI: 1.54-2.31, for BMI≥30 vs. <20), while the association tended to be inverse in younger women. A high mammographic density increased breast cancer risk (OR = 2.61, 95% CI: 2.02-3.38 for density >75% vs. adipose tissue). The ORs were 1.67 (95% CI: 1.47-1.89) and 2.04 (95% CI: 1.38-3.00) for one first-degree relative and two or more relatives affected by breast cancer, respectively. Our study confirms the role of major recognized risk factors for breast cancer in our population and provides the basis for a stratification of the participants in the mammographic screening according to different levels of risk. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Clinical risk factors for death after release from prison in Washington State: A nested case control study

PubMed Central

Binswanger, Ingrid A.; Stern, Marc F.; Yamashita, Traci E.; Mueller, Shane R.; Baggett, Travis P.; Blatchford, Patrick J.

2015-01-01

Background and aims While mortality rates after prison release are high, little is known about clinical risk factors for death. We sought to identify risk and protective factors for all-cause and accidental poisoning (overdose) death. Design Nested case control study of people released from prison. Setting Washington State Department of Corrections, Washington, USA. Participants Cases (699 all-cause deaths, of which 88 were among women, and 206 additional overdose deaths, of which 76 were among women) between 1999 and 2009 matched 1:1 to controls on sex, age and year of release using risk set sampling. Measurements Prison medical charts were abstracted for clinical information. Independent associations between clinical characteristics and all-cause and overdose mortality were assessed using conditional logistic regression. Findings Key independent risk factors for all-cause mortality included homelessness (Odds Ratio [OR] 1.53, 95% Confidence Interval [CI] 1.06, 2.23), injection drug use (OR 1.54, 95% CI 1.15, 2.05), tobacco use (OR 1.50, 95% CI 1.06, 2.12), cirrhosis (OR 4.42, 95% CI 1.63, 11.98), and psychiatric medications before release (OR 2.37, 95% CI 1.71, 3.29). Independent risk factors for overdose mortality included substance dependence (OR 2.33, 95% CI 1.32, 4.11), injection drug use (OR 2.43, 95% CI 1.53, 3.86), panic disorder (OR 3.87, 95% CI 1.62, 9.21), psychiatric prescriptions before release (OR 2.44, 95% CI 1.55, 3.85), and problems with opiates/sedatives (OR 2.81, 95% CI 1.40, 5.63). Substance use disorder treatment during the index incarceration was protective for all-cause (OR 0.67, 95% CI 0.49, 0.91) and overdose (OR 0.57, 95% CI 0.35, 0.90) mortality. Conclusions Injection drug use and substance use disorders are risk factors for death after release from prison. In-prison substance use treatment services may reduce the risk. PMID:26476210

Respiratory effect of beta-blockers in people with asthma and cardiovascular disease: population-based nested case control study.

PubMed

Morales, Daniel R; Lipworth, Brian J; Donnan, Peter T; Jackson, Cathy; Guthrie, Bruce

2017-01-27

Cardiovascular disease (CVD) is a common comorbidity in people with asthma. However, safety concerns have caused heterogeneity in clinical guideline recommendations over the use of cardioselective beta-blockers in people with asthma and CVD, partly because risk in the general population has been poorly quantified. The aim of this study was to measure the risk of asthma exacerbations with beta-blockers prescribed to a general population with asthma and CVD. Linked data from the UK Clinical Practice Research Datalink was used to perform nested case-control studies among people with asthma and CVD matched on age, sex and calendar time. Adjusted incidence rate ratios (IRR) were calculated for the association between oral beta-blocker use and moderate asthma exacerbations (rescue oral steroids) or severe asthma exacerbations (hospitalisation or death) using conditional logistic regression. The cohort consisted of 35,502 people identified with active asthma and CVD, of which 14.1% and 1.2% were prescribed cardioselective and non-selective beta-blockers, respectively, during follow-up. Cardioselective beta-blocker use was not associated with a significantly increased risk of moderate or severe asthma exacerbations. Consistent results were obtained following sensitivity analyses and a self-controlled case series approach. In contrast, non-selective beta-blockers were associated with a significantly increased risk of moderate asthma exacerbations when initiated at low to moderate doses (IRR 5.16, 95% CI 1.83-14.54, P = 0.002), and both moderate and severe exacerbations when prescribed chronically at high dose (IRR 2.68, 95% CI 1.08-6.64, P = 0.033 and IRR 12.11, 95% CI 1.02-144.11, P = 0.048, respectively). Cardioselective beta-blockers prescribed to people with asthma and CVD were not associated with a significantly increased risk of moderate or severe asthma exacerbations and potentially could be used more widely when strongly indicated.

Prediagnostic serum calcium and albumin and ovarian cancer: A nested case-control study in the Norwegian Janus Serum Bank Cohort.

PubMed

Schwartz, Gary G; Tretli, Steinar; Vos, Linda; Robsahm, Trude E

2017-08-01

Women with higher serum calcium may be more likely to be diagnosed and die of ovarian cancer. We evaluated that finding in a large, prospective cohort. We conducted a nested case-control study using a population-based biobank from Norway. We compared 202 ovarian cancer cases and 202 controls, matched for age, date at blood draw, and county of residence, with respect to serum calcium and albumin, adjusted for anthropometric variables. We evaluated risks using the entire follow-up period as well as 2-15 years and 16-25 years ("early" and "late", respectively). For the entire follow-up, risk was significantly increased in the highest tertile of albumin and for high albumin and calcium jointly. Risks for ovarian cancer differed markedly by follow-up time. In early follow-up, women in the highest tertile of serum calcium had a 2.5-fold increased risk, adjusted for height and body mass index (OR=2.47, 95% C.I. 1.12-5.45) with a significant dose-response (p=0.024). Risk was not elevated in late follow-up (OR=0.62, 95% C.I. 0.27-1.36). Similarly, in early follow-up, women in the highest tertile of serum albumin had an increased risk (OR=2.55, 95% C.I.1.22-5.49) with a significant dose-response (p=0.009). Conversely, risk was not increased in late follow-up (OR=1.36, 95% C.I. 0.65-2.83). These data confirm a prospective association between higher serum calcium and ovarian cancer. An association in early, but not late, follow-up suggests that the higher calcium reflects the presence of existing cancer. A positive association with serum albumin is novel and should be interpreted cautiously. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Risk of bleeding and antibiotic use in patients receiving continuous phenprocoumon therapy. A case-control study nested in a large insurance- and population-based German cohort.

PubMed

Abbas, Sascha; Ihle, Peter; Harder, Sebastian; Schubert, Ingrid

2014-05-05

There is major concern about coumarins interacting with various drug classes and increasing the risk of overanticoagulation. The aim of the study was to assess bleeding risk in patients with concurrent use of antibiotics and phenprocoumon, the most widely prescribed coumarin in many European countries. We conducted a nested-case-control study within a cohort of 513,338 incident and continuous phenprocoumon users ≥ 18 years of age using claims data of the statutory health insurance company AOK, covering 30% of the German population. Bleeding risk associated with current use of antibiotics for systemic use (antibacterials/antimycotics) was calculated using conditional logistic regression in 13,785 cases with a bleeding event and 55,140 risk-set sampling-matched controls. Bleeding risk associated with any antibacterial use in phenprocoumon users was significantly increased [odds ratio (OR) 2.37, 95% confidence interval (CI) 2.20-2.56]. The association was stronger for gastrointestinal than for cerebral bleeding (OR 2.09, 95% CI 1.84-2.38 and OR 1.34, 95% CI 1.03-1.74, respectively) and highest for other/unspecified bleeding (OR 2.92, 95% CI 2.62-3.26). Specific antibiotic classes were strongly associated with bleeding risk, e.g. cotrimoxazole (OR 3.86, 95% CI 3.08-4.84) and fluorquinolones (OR 3.13, 95% CI 2.74-3.59), among those highest for ofloxacin (OR 5.00, 95% CI 3.01-8.32). Combined use of phenprocoumon and antimycotics was not significantly associated with bleeding risk. Risk was not significantly modified by age (pint=0.25) or sex (pint=0.96). The association was stronger the closer the antibiotic exposure was to the bleeding event. Among continuous phenprocoumon users, antibiotics - particularly quinolones and cotrimoxazole - should be prescribed after careful consideration due to an increased bleeding risk. Close monitoring of international normalised ratio levels after prescription is recommended.

Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: a nested case-control study: plasma micronutrients and pancreatic cancer risk.

PubMed

Jeurnink, Suzanne M; Ros, Martine M; Leenders, Max; van Duijnhoven, Franzel J B; Siersema, Peter D; Jansen, Eugene H J M; van Gils, Carla H; Bakker, Marije F; Overvad, Kim; Roswall, Nina; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Racine, Antoine; Cadeau, Claire; Grote, Verena; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Valanou, Elisavet; Palli, Domenico; Krogh, Vittorio; Vineis, Paolo; Tumino, Rosario; Mattiello, Amalia; Weiderpass, Elisabete; Skeie, Guri; Castaño, José María Huerta; Duell, Eric J; Barricarte, Aurelio; Molina-Montes, Esther; Argüelles, Marcial; Dorronsoro, Mire; Johansen, Dorthe; Lindkvist, Björn; Sund, Malin; Crowe, Francesca L; Khaw, Kay-Tee; Jenab, Mazda; Fedirko, Veronika; Riboli, E; Bueno-de-Mesquita, H B

2015-03-15

Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (α- and β-carotene, lycopene, β-cryptoxanthin, canthaxanthin, zeaxanthin and lutein), α- and γ-tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma β-carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend = 0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend = 0.06) and α-tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend = 0.08. For α- and β-carotene, lutein, sum of carotenoids and γ-tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of β-carotene, zeaxanthin and α-tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted. © 2014 UICC.

Polymorphisms of genes coding for ghrelin and its receptor in relation to anthropometry, circulating levels of IGF-I and IGFBP-3, and breast cancer risk: a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC).

PubMed

Dossus, Laure; McKay, James D; Canzian, Federico; Wilkening, Stefan; Rinaldi, Sabina; Biessy, Carine; Olsen, Anja; Tjønneland, Anne; Jakobsen, Marianne U; Overvad, Kim; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Fournier, Agnes; Linseisen, Jakob; Lukanova, Annekatrin; Boeing, Heiner; Fisher, Eva; Trichopoulou, Antonia; Georgila, Christina; Trichopoulos, Dimitrios; Palli, Domenico; Krogh, Vittorio; Tumino, Rosario; Vineis, Paolo; Quirós, José Ramon; Sala, Núria; Martínez-García, Carmen; Dorronsoro, Miren; Chirlaque, Maria-Dolores; Barricarte, Aurelio; van Duijnhoven, Fränzel J B; Bueno-de-Mesquita, H B; van Gils, Carla H; Peeters, Petra H M; Hallmans, Göran; Lenner, Per; Bingham, Sheila; Khaw, Kay Tee; Key, Tim J; Travis, Ruth C; Ferrari, Pietro; Jenab, Mazda; Riboli, Elio; Kaaks, Rudolf

2008-07-01

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, has two major functions: the stimulation of the growth hormone production and the stimulation of food intake. Accumulating evidence also suggests a role of ghrelin in cancer development. We conducted a case-control study on 1359 breast cancer cases and 2389 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition, to examine the association of common genetic variants in the genes coding for ghrelin (GHRL) and its receptor (GHSR) with anthropometric measures, circulating insulin growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 and breast cancer risk. Pair-wise tagging was used to select the 15 polymorphisms that represent the majority of common genetic variants across the GHRL and GHSR genes. A significant increase in breast cancer risk was observed in carriers of the GHRL rs171407-G allele (odds ratio: 1.2; 95% confidence interval: 1.0-1.4; P = 0.02). The GHRL single-nucleotide polymorphism rs375577 was associated with a 5% increase in IGF-I levels (P = 0.01). A number of GHRL and GHSR polymorphisms were associated with body mass index (BMI) and height (P between <0.01 and 0.04). The false-positive report probability (FPRP) approach suggests that these results are noteworthy (FPRP < 0.20). The results presented here add to a growing body of evidence that GHRL variations are associated with BMI. Furthermore, we have observed evidence for association of GHRL polymorphisms with circulating IGF-I levels and with breast cancer risk. These associations, however, might also be due to chance findings and further large studies are needed to confirm our results.

Regular Use of Aspirin or Non-Aspirin Nonsteroidal Anti-Inflammatory Drugs Is Not Associated With Risk of Incident Pancreatic Cancer in Two Large Cohort Studies.

PubMed

Khalaf, Natalia; Yuan, Chen; Hamada, Tsuyoshi; Cao, Yin; Babic, Ana; Morales-Oyarvide, Vicente; Kraft, Peter; Ng, Kimmie; Giovannucci, Edward; Ogino, Shuji; Stampfer, Meir; Cochrane, Barbara B; Manson, JoAnn E; Clish, Clary B; Chan, Andrew T; Fuchs, Charles S; Wolpin, Brian M

2018-04-01

Use of aspirin and/or non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) reduces the risk of several cancers, but it is not clear if use of these drugs is associated with risk of pancreatic cancer. We evaluated aspirin and non-aspirin NSAID use and risk of pancreatic adenocarcinoma in 141,940 participants from the Health Professionals Follow-up Study and Nurses' Health Study using multivariable-adjusted Cox proportional hazards regression. We considered several exposure classifications to model differing lag times between NSAID exposure and cancer development. We also conducted a nested case-control study of participants from 3 prospective cohorts using conditional logistic regression to evaluate pre-diagnosis levels of plasma salicylurate, a major metabolite of aspirin, in 396 pancreatic cancer cases and 784 matched individuals without pancreatic cancer (controls). In the prospective cohort study, 1122 participants developed pancreatic adenocarcinoma over 4.2 million person-years. Use of aspirin or non-aspirin NSAIDs was not associated with pancreatic cancer risk, even after considering several latency exposure classifications. In a pre-planned subgroup analysis, regular aspirin use was associated with reduced pancreatic cancer risk among participants with diabetes (relative risk, 0.71; 95% CI, 0.54-0.94). In the nested case-control study, pre-diagnosis levels of salicylurate were not associated with pancreatic cancer risk (odds ratio, 1.08; 95% CI, 0.72-1.61; P trend 0.81; comparing participants in the highest quintile with those in the lowest quintile of plasma salicylurate). Regular aspirin or non-aspirin NSAID use was not associated with future risk of pancreatic cancer in participants from several large prospective cohort studies. A possible reduction in risk for pancreatic cancer among people with diabetes who regularly use aspirin should be further examined in preclinical and human studies. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Lung cancer among glass fibre production workers: a case-control study.

PubMed Central

Gardner, M J; Magnani, C; Pannett, B; Fletcher, A C; Winter, P D

1988-01-01

A cohort study among 4734 employees at an English glass fibre plant previously reported no excess of lung cancer mortality either overall or when examined in broad occupational groups. To investigate occupation in more detail, and to test the hypothesis that processes producing or using finer (respirable) fibres may be related to a higher risk of lung cancer, a nested case-control study has now been carried out. Included are 73 cases of lung cancer and 506 matched controls, for whom jobs held and processes worked on have been blindly recorded in more detail than for the cohort study. Workers known to have been employed on processes containing respirable fibres had a relative risk of lung cancer of 1.2 (95% confidence interval 0.7-2.0) compared with other workers. There was no evidence of a relationship of lung cancer to fibre diameter, duration of exposure, or time since first exposure. The results by broad occupational group were similar to those of the cohort study, and although some of the many detailed occupational categories examined had significantly raised relative risks, these did not appear to be related to exposure to respirable glass fibre. Although the study has not indicated a differential risk of lung cancer among workers exposed to finer diameter glass fibres, the exposure levels were low and the number of cases small. PMID:3179236

Association Between Smoking Status, Preoperative Exhaled Carbon Monoxide Levels, and Postoperative Surgical Site Infection in Patients Undergoing Elective Surgery

PubMed Central

Martin, David P.; Thompson, Rodney; Schroeder, Darrell R.; Hanson, Andrew C.; Warner, David O.

2017-01-01

Importance Cigarette smoking is a risk factor for many perioperative complications, including surgical site infection (SSI). The duration of abstinence from smoking required to reduce this risk is unknown. Objectives To evaluate if abstinence from smoking on the day of surgery is associated with a decreased frequency of SSI in patients who smoke cigarettes and to confirm that smoking is significantly independently associated with SSI when adjustment is made for potentially relevant covariates, such as body mass index. Design, Setting, and Participants In this observational, nested, matched case-control study, 2 analyses were performed at an academic referral center in the upper Midwest. Cases included all patients undergoing elective surgical procedures at Mayo Clinic, Rochester, Minnesota, between January 1, 2009, and July 31, 2014 (inclusive) who subsequently developed an SSI. Controls for both analyses were matched on age, sex, and type of surgery. Exposures Smoking status and preoperative exhaled carbon monoxide level, assessed by nurses in the preoperative holding area. Patients were classified as smoking on the day of surgery if they self-reported smoking or if their preoperative exhaled carbon monoxide level was 10 ppm or higher. Main Outcomes and Measures Surgical site infection after a surgical procedure at Mayo Clinic, Rochester, as identified by routine clinical surveillance using National Healthcare Safety Network criteria. Results Of the 6919 patients in the first analysis, 3282 (47%) were men and 3637 (53%) were women; median age (interquartile range) for control and SSI cases was 60 (48-70). Of the 392 patients in the second analysis, 182 (46%) were men and 210 (54%) were women; median age (interquartile range) for controls was 53 (45-49) and for SSI cases was 51 (45-60). During the study period, approximately 2% of surgical patients developed SSI annually. Available for the first analysis (evaluating the influence of current smoking status) were 2452 SSI cases matched to 4467 controls. The odds ratio for smoking and SSI was 1.51 (95% CI, 1.20-1.90; P < .001), which remained statistically significant after adjusting for covariates. In the second analysis (evaluating the influence of smoking on the day of surgery), there were 137 SSI cases matched to 255 controls. The odds ratio for smoking on the day of surgery and SSI was 1.96 (95% CI, 1.23-3.13; P < .001), which remained statistically significant after adjusting for covariates. Preoperative exhaled carbon monoxide level was not associated with the frequency of SSI, suggesting that the association between smoking on the day of surgery and SSI was not related to preoperative exhaled carbon monoxide levels. Conclusions and Relevance Current smoking is associated with the development of SSI, and smoking on the day of surgery is independently associated with the development of SSI. These data cannot distinguish whether abstinence per se reduces risk or whether it is associated with other factors that may be causative. PMID:28199450

Early diagnosis of typhoid fever by nested PCR for flagellin gene of Salmonella enterica serotype Typhi.

PubMed

Khan, S; Harish, B N; Menezes, G A; Acharya, N S; Parija, S C

2012-11-01

Typhoid fever caused by Salmonella Typhi continues to be a major health problem in spite of the use of antibiotics and the development of newer antibacterial drugs. Inability to make an early laboratory diagnosis and resort to empirical therapy, often lead to increased morbidity and mortality in cases of typhoid fever. This study was aimed to optimize a nested PCR for early diagnosis of typhoid fever and using it as a diagnostic tool in culture negative cases of suspected typhoid fever. Eighty patients with clinical diagnosis of typhoid fever and 40 controls were included in the study. The blood samples collected were subjected to culture, Widal and nested PCR targeting the flagellin gene of S. Typhi. The sensitivity of PCR on blood was found to be 100 per cent whereas the specificity was 76.9 per cent. The positive predictive value (PPV) of PCR was calculated to be 76.9 per cent with an accuracy of 86 per cent. None of the 40 control samples gave a positive PCR. Due to its high sensitivity and specificity nested PCR can be used as a useful tool to diagnose clinically suspected, culture negative cases of typhoid fever.

Inclusion of persons with disabilities in systems of social protection: a population-based survey and case–control study in Peru

PubMed Central

Bernabe-Ortiz, Antonio; Diez-Canseco, Francisco; Vasquez, Alberto; Kuper, Hannah; Walsham, Matthew; Blanchet, Karl

2016-01-01

Objective This study aims to assess the needs of people with disabilities and their level of inclusion in social protection programmes. Design Population based-survey with a nested case–control study. Setting Morropon, a semiurban district located in Piura, northern Peru. Participants For the population survey, a two-stage sampling method was undertaken using data from the most updated census available and information of each household member aged ≥5 years was collected. In the nested case–control study, only one participant, case or control, per household was included in the study. Primary and secondary outcome measures Disability was screened using the Washington Group short questionnaire. A case, defined as an individual aged ≥5 years with disabilities, was matched with one control without disabilities by sex and age (±5 years). Information was collected on socioeconomic status, education, health and rehabilitation and social protection participation. Results The survey included 3684 participants, 1848 (50.1%) females, mean age: 36.4 (SD: 21.7). A total of 290 participants (7.9%; 95% CI 7.0% to 8.7%) were classified as having disability. Adults with disabilities were more likely to be single (OR=3.40; 95% CI 1.54 to 7.51) and not to be working (OR=4.36; 95% CI 2.26 to 8.40), while those who did work were less likely to receive the national minimum wage (ie, 750 PEN or about US$265; p=0.007). People with disabilities were more likely to experience health problems. There was no difference between those enrolled in any social protection programme among participants with and without disabilities. Conclusions People with disabilities were found to have higher needs for social protection, but were not more likely to be enrolled in social protection programmes. The Peruvian social protection system should consider adding disability status to selection criteria in their cash transfer programmes as well as implementing disability-specific interventions. PMID:27566630

Demonstration of EnergyNest thermal energy storage (TES) technology

NASA Astrophysics Data System (ADS)

Hoivik, Nils; Greiner, Christopher; Tirado, Eva Bellido; Barragan, Juan; Bergan, Pâl; Skeie, Geir; Blanco, Pablo; Calvet, Nicolas

2017-06-01

This paper presents the experimental results from the EnergyNest 2 × 500 kWhth thermal energy storage (TES) pilot system installed at Masdar Institute of Science & Technology Solar Platform. Measured data are shown and compared to simulations using a specially developed computer program to verify the stability and performance of the TES. The TES is based on a solid-state concrete storage medium (HEATCRETE®) with integrated steel tube heat exchangers cast into the concrete. The unique concrete recipe used in the TES has been developed in collaboration with Heidelberg Cement; this material has significantly higher thermal conductivity compared to regular concrete implying very effective heat transfer, at the same time being chemically stable up to 450 °C. The demonstrated and measured performance of the TES matches the predictions based on simulations, and proves the operational feasibility of the EnergyNest concrete-based TES. A further case study is analyzed where a large-scale TES system presented in this article is compared to two-tank indirect molten salt technology.

Aetiology of childhood pneumonia in a well vaccinated South African birth cohort: a nested case-control study

PubMed Central

Zar, HJ; Barnett, W; Stadler, A; Gardner-Lubbe, S; Myer, L; Nicol, MP

2016-01-01

Background Pneumonia is a leading cause of mortality and morbidity in children globally. The aetiology of pneumonia following introduction of 13-valent pneumococcal conjugate vaccine (PCV13) has not been well studied in low- and middle-income countries; furthermore most data is from cross-sectional studies of hospitalized cases. We aimed to longitudinally investigate the incidence and aetiology of childhood pneumonia in a South African birth cohort. Methods Children in the Drakenstein Child Health Study were followed from birth from May 2012 to Dec 2014. Immunizations included acellular pertussis vaccine and PCV13. A nested subgroup had nasopharyngeal swabs (NPs) collected 2-weekly through infancy. Pneumonia episodes were identified and blood, NPs and induced sputum (IS) specimens obtained. Multiplex real-time PCR for pathogens was done on NPs and IS of pneumonia cases and on NPs of age- and site-matched controls. Associations between organisms and pneumonia used conditional logistic regression; results are presented as odds ratios (OR) with 95% confidence intervals (CI). Findings Overall 314 pneumonia cases occurred (incidence 0·27 episodes per child year (e/cy); median age 5 months) in 967 children during 1145 child-years of follow-up. Severe pneumonia occurred in 60 (21%) of cases (incidence 0·07 e/cy) with a case fatality ratio of 1%. A median of 5 organisms were detected in cases and controls with a median of 6 on IS (p=0·48 compared to NPs). Bordetella pertussis [OR 11·08; 95% CI 1·33-92·54; 7/696 positive], Respiratory Syncytial Virus [OR 8·05; 95% CI 4·21-15·38; 83/696 positive] or influenza virus [OR 4·13; 95% CI 2·06-8·26; 43/696 positive] were most strongly associated with pneumonia; bocavirus, parainfluenza virus, adenovirus, cytomegalovirus and Haemophilus influenzae. were also associated with pneumonia. In cases, testing of IS in addition to NPs provided incremental yield for B. pertussis and several viruses. Interpretation Pneumonia remains common in this highly vaccinated population. RSV was the most frequently detected pathogen associated with pneumonia; influenza virus and B. pertussis were also strongly associated with pneumonia. Testing of IS increases the yield for several organisms. New vaccines and strategies are needed to address the burden of childhood pneumonia. PMID:27117547

Rotenone, Paraquat, and Parkinson’s Disease

PubMed Central

Tanner, Caroline M.; Kamel, Freya; Ross, G. Webster; Hoppin, Jane A.; Goldman, Samuel M.; Korell, Monica; Marras, Connie; Bhudhikanok, Grace S.; Kasten, Meike; Chade, Anabel R.; Comyns, Kathleen; Richards, Marie Barber; Meng, Cheryl; Priestley, Benjamin; Fernandez, Hubert H.; Cambi, Franca; Umbach, David M.; Blair, Aaron; Sandler, Dale P.; Langston, J. William

2011-01-01

Background Mitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson’s disease (PD). Certain pesticides may affect these mechanisms, but no pesticide has been definitively associated with PD in humans. Objectives Our goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans. Methods We assessed lifetime use of pesticides selected by mechanism in a case–control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controls: one case. Results In 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I [odds ratio (OR) = 1.7; 95% confidence interval (CI), 1.0–2.8] including rotenone (OR = 2.5; 95% CI, 1.3–4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2–3.6), including paraquat (OR = 2.5; 95% CI, 1.4–4.7). Conclusions PD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally—those that impair mitochondrial function and those that increase oxidative stress—supporting a role for these mechanisms in PD pathophysiology. PMID:21269927

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.

Proteomic Profiling of Serial Prediagnostic Serum Samples for Early Detection of Colon Cancer in the U.S. Military.

PubMed

Shao, Stephanie; Neely, Benjamin A; Kao, Tzu-Cheg; Eckhaus, Janet; Bourgeois, Jolie; Brooks, Jasmin; Jones, Elizabeth E; Drake, Richard R; Zhu, Kangmin

2017-05-01

Background: Serum proteomic biomarkers offer a promising approach for early detection of cancer. In this study, we aimed to identify proteomic profiles that could distinguish colon cancer cases from controls using serial prediagnostic serum samples. Methods: This was a nested case-control study of active duty military members. Cases consisted of 264 patients diagnosed with colon cancer between 2001 and 2009. Controls were matched to cases on age, gender, race, serum sample count, and collection date. We identified peaks that discriminated cases from controls using random forest data analysis with a 2/3 training and 1/3 validation dataset. We then included epidemiologic data to see whether further improvement of model performance was obtainable. Proteins that corresponded to discriminatory peaks were identified. Results: Peaks with m/z values of 3,119.32, 2,886.67, 2,939.23, and 5,078.81 were found to discriminate cases from controls with a sensitivity of 69% and a specificity of 67% in the year before diagnosis. When smoking status was included, sensitivity increased to 76% while histories of other cancer and tonsillectomy raised specificity to 76%. Peaks at 2,886.67 and 3,119.32 m/z were identified as histone acetyltransferases while 2,939.24 m/z was a transporting ATPase subunit. Conclusions: Proteomic profiles in the year before cancer diagnosis have the potential to discriminate colon cancer patients from controls, and the addition of epidemiologic information may increase the sensitivity and specificity of discrimination. Impact: Our findings indicate the potential value of using serum prediagnostic proteomic biomarkers in combination with epidemiologic data for early detection of colon cancer. Cancer Epidemiol Biomarkers Prev; 26(5); 711-8. ©2016 AACR . ©2016 American Association for Cancer Research.

Fatal motor vehicle crashes among veterans of the 1991 Gulf War and exposure to munitions demolitions at Khamisiyah: a nested case-control study.

PubMed

Gackstetter, Gary D; Hooper, Tomoko I; DeBakey, Samar F; Johnson, Amy; Nagaraj, Barbara E; Heller, Jack M; Kang, Han K

2006-04-01

A proposed explanation for the observed higher risk of fatal motor vehicle crashes (MVC) among 1991 Gulf War-deployed veterans is neurocognitive deficits resulting from nerve agent exposure at Khamisiyah, Iraq. Our objective was to assess any association between postwar fatal MVC and possible nerve agent exposure based on 2000 modeled plume data. Cases were defined as MVC deaths with a record in the Department of Transportation Fatality Analysis Reporting System through 1995. Cases (n = 282) and controls (n = 3,131) were derived from a larger nested case-control study of Gulf War-era veterans and limited to Army, male, deployed personnel. Exposure and cumulative dose by case-control status were analyzed using multivariate techniques. Exposure status was not associated with fatal MVC (OR 0.96, 95% CI 0.72-1.26), nor were tertiles of cumulative dose. Findings do not support an association between possible exposures at Khamisiyah and postwar fatal MVC among Gulf War veterans.

A concordance index for matched case-control studies with applications in cancer risk.

PubMed

Brentnall, Adam R; Cuzick, Jack; Field, John; Duffy, Stephen W

2015-02-10

In unmatched case-control studies, the area under the receiver operating characteristic (ROC) curve (AUC) may be used to measure how well a variable discriminates between cases and controls. The AUC is sometimes used in matched case-control studies by ignoring matching, but it lacks interpretation because it is not based on an estimate of the ROC for the population of interest. We introduce an alternative measure of discrimination that is the concordance of risk factors conditional on the matching factors. Parametric and non-parametric estimators are given for different matching scenarios, and applied to real data from breast and lung cancer case-control studies. Diagnostic plots to verify the constancy of discrimination over matching factors are demonstrated. The proposed simple measure is easy to use, interpret, more efficient than unmatched AUC statistics and may be applied to compare the conditional discrimination performance of risk factors. Copyright © 2014 John Wiley & Sons, Ltd.

Risk factors for epilepsy in Bas-Uélé Province, Democratic Republic of the Congo: a case-control study.

PubMed

Colebunders, Robert; Mandro, Michel; Mokili, John L; Mucinya, Gisele; Mambandu, Germain; Pfarr, Kenneth; Reiter-Owona, Ingrid; Hoerauf, Achim; Tepage, Floribert; Levick, Bethanie; Begon, Michael; Laudisoit, Anne

2016-08-01

The reason for the high prevalence of epilepsy in onchocerciasis endemic areas remains unknown. The aim of this study was to detect risk factors associated with epilepsy in a region endemic for onchocerciasis. In June 2014, a case-control study was performed in Titule, Bas-Uélé Province in the Democratic Republic of the Congo. Individuals with unprovoked convulsive epilepsy of unknown aetiology were enrolled as cases (n=59). Healthy members of families without cases of epilepsy in the same village were recruited as controls (n=61). A multivariate binomial logistic regression analysis was performed to identify potential risk factors associated with epilepsy. To evaluate the potential protective effect of ivermectin treatment on the development of epilepsy, a nested age-matched case-control study was performed including only those who were eligible for ivermectin treatment in the year before they developed epilepsy. Suspected onchocerciasis skin lesions were more often present in cases than in controls: 12/41 (29%) vs. 1/56 (2%), respectively (odds ratio (OR) 20.26, 95% confidence interval (CI) 2.42-170; p<0.01). Ivermectin had been taken 7 months earlier in 29/59 (49%) cases and 29/61 (48%) controls. Onchocerca volvulus (OV) DNA was detected by PCR in skin snips in 26/34 cases (76%) and 10/14 controls (71%) (p=0.7), and there was presence of OV IgG4 antibodies in 35/48 (73%) cases and 15/18 (83%) controls (p=0.5). OV DNA was not detected in the cerebrospinal fluid of cases (controls not tested). Both cases and controls reported frequent bites by blackflies (Diptera, Simuliidae). Bathing daily as opposed to less often (OR 16.7, 95% CI 2.2-125.8; p<0.01), bathing between 11 a.m. and 4 p.m. (OR 12.7, 95% CI 1.6-103.7; p=0.02), and washing clothes between 11 a.m. and 4 p.m. (OR 10.9, 95% CI 1.5-77.3; p=0.02) were all independently associated with epilepsy. Blood screening by specific PCR tests for Toxoplasma and Wuchereria bancrofti was negative in all cases and controls. A Loa loa infestation was found in only one case and one control by PCR and Giemsa smear. Antibodies to Taenia solium, Toxocara, and Trypanosoma sp were not detected in any of the participants. In an age-matched case-control analysis, 16/18 (89%) cases had not taken ivermectin the year before they developed epilepsy, compared to 7/18 (39%) controls that same year (p=0.002). These data suggest that frequent activities at rivers known to be blackfly breeding sites and a historical lack of ivermectin treatment were risk factors for epilepsy in this onchocerciasis endemic area. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Acute kidney injury and edaravone in acute ischemic stroke: the Fukuoka Stroke Registry.

PubMed

Kamouchi, Masahiro; Sakai, Hironori; Kiyohara, Yutaka; Minematsu, Kazuo; Hayashi, Kunihiko; Kitazono, Takanari

2013-11-01

A free radical scavenger, edaravone, which has been used for the treatment of ischemic stroke, was reported to cause acute kidney injury (AKI) as a fatal adverse event. The aim of the present study was to clarify whether edaravone is associated with AKI in patients with acute ischemic stroke. From the Fukuoka Stroke Registry database, 5689 consecutive patients with acute ischemic stroke who were hospitalized within 24 hours of the onset of symptoms were included in this study. A logistic regression analysis for the Fukuoka Stroke Registry cohort was done to identify the predictors for AKI. A propensity score-matched nested case-control study was also performed to elucidate any association between AKI and edaravone. Acute kidney injury occurred in 128 of 5689 patients (2.2%) with acute ischemic stroke. A multivariate analysis revealed that the stroke subtype, the basal serum creatinine level, and the presence of infectious complications on admission were each predictors of developing AKI. In contrast, a free radical scavenger, edaravone, reduced the risk of developing AKI (multivariate-adjusted odds ratio [OR] .45, 95% confidence interval [CI] .30-.67). Propensity score-matched case-control study confirmed that edaravone use was negatively associated with AKI (propensity score-adjusted OR .46, 95% CI .29-.74). Although AKI has a significant impact on the clinical outcome of hospital inpatients, edaravone has a protective effect against the development of AKI in patients with acute ischemic stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Whip use and race progress are associated with horse falls in hurdle and steeplechase racing in the UK.

PubMed

Pinchbeck, G L; Clegg, P D; Proudman, C J; Morgan, K L; French, N R

2004-07-01

Falls during racing present a risk of injury to both horse and jockey and a risk of fatality to horses. To use video recordings of races to describe the circumstances surrounding horse falls at hurdle and steeplechase fences and to identify and quantify within-race risk factors for horse falls in National Hunt racing in the UK. A retrospective, matched, nested case-control study using video recordings of races was conducted on 6 UK racecourses. Cases and controls were matched on both race type and jump number at which the fall occurred. Conditional logistic regression analysis was used to examine the univariable and multivariable relationship between predictor variables and the risk of falling. The risk of falling was significantly associated with whip use and race progress. Horses which were being whipped and progressing through the race were at greater than 7 times the risk of falling compared to horses which were not being whipped and which had no change in position or lost position through the field. This study has identified whip use and the position of the horse with respect to others in the field as potential risk factors for horse falls. If these findings are confirmed by the use of intervention trials (e.g. with whip-free or restricted whip use races), modifications could be introduced which would reduce the frequency of horse falls, leading to improved equine welfare.

Risk Factors for Symptomatic Avascular Necrosis in Childhood-onset Systemic Lupus Erythematosus.

PubMed

Yang, Yelin; Kumar, Sathish; Lim, Lily Siok Hoon; Silverman, Earl D; Levy, Deborah M

2015-12-01

To examine the frequency and risk factors for symptomatic avascular necrosis (AVN) in childhood-onset systemic lupus erythematosus (cSLE). A single-center, nested, matched, case-control design was used. There were 617 patients with cSLE followed at the Hospital for Sick Children (SickKids) Lupus Clinic between July 1982 and June 2013 included in the study. The AVN cohort consisted of 37 patients identified with clinical findings of symptomatic AVN and diagnosis was confirmed by 1 or more imaging modalities. Three controls were matched to each patient with AVN by date and age at diagnosis. Baseline clinical, laboratory, and treatment characteristics were compared between patients with AVN and controls by univariable analyses and if statistically significant, were included in a multivariable logistic regression model. A total of 37/617 patients (6%) developed symptomatic AVN in 91 joints during followup at SickKids. The mean duration to disease was 2.3 years. The hip was the most commonly involved joint (26/37, 70%). Compared with the matched non-AVN cohort, patients with AVN had a higher incidence of central nervous system (CNS) involvement and nephritis, required greater cumulative prednisone (PRED) from cSLE diagnosis to AVN, received a greater maximal daily PRED dose, and had more frequent use of pulse methylprednisolone therapy. Multivariable regression analysis confirmed major organ involvement (CNS disease and/or nephritis) and maximal daily PRED dose as significant predictors of symptomatic AVN development. Patients with cSLE with severe organ involvement including nephritis and CNS disease and higher maximal daily dose of PRED are more likely to develop symptomatic AVN.

Nest covering in plovers: How modifying the visual environment influences egg camouflage.

PubMed

Troscianko, Jolyon; Wilson-Aggarwal, Jared; Spottiswoode, Claire N; Stevens, Martin

2016-10-01

Camouflage is one of the most widespread antipredator defences, and its mechanistic basis has attracted considerable interest in recent years. The effectiveness of camouflage depends on the interaction between an animal's appearance and its background. Concealment can therefore be improved by changes to an animal's own appearance, by behaviorally selecting an optimal background, or by modifying the background to better match the animal's own appearance. Research to date has largely focussed on the first of these mechanisms, whereas there has been little work on the second and almost none on the third. Even though a number of animal species may potentially modify their environment to improve individual-specific camouflage, this has rarely if ever been quantitatively investigated, or its adaptive value tested. Kittlitz's plovers (Charadrius pecuarius) use material (stones and vegetation) to cover their nests when predators approach, providing concealment that is independent of the inflexible appearance of the adult or eggs, and that can be adjusted to suit the local surrounding background. We used digital imaging and predator vision modeling to investigate the camouflage properties of covered nests, and whether their camouflage affected their survival. The plovers' nest-covering materials were consistent with a trade-off between selecting materials that matched the color of the eggs, while resulting in poorer nest pattern and contrast matching to the nest surroundings. Alternatively, the systematic use of materials with high-contrast and small-pattern grain sizes could reflect a deliberate disruptive coloration strategy, whereby high-contrast material breaks up the telltale outline of the clutch. No camouflage variables predicted nest survival. Our study highlights the potential for camouflage to be enhanced by background modification. This provides a flexible system for modifying an animal's conspicuousness, to which the main limitation may be the available materials rather than the animal's appearance.

Cardiovascular health status and metabolic syndrome in Ecuadorian natives/Mestizos aged 40 years or more with and without stroke and ischemic heart disease--an atahualpa project case-control nested study.

PubMed

Del Brutto, Oscar H; Mera, Robertino M; Montalván, Martha; Del Brutto, Victor J; Zambrano, Mauricio; Santamaría, Milton; Tettamanti, Daniel

2014-04-01

Knowledge of regional-specific cardiovascular risk factors is mandatory to reduce the growing burden of stroke and ischemic heart disease in Latin American populations. We conducted a population-based case-control study to assess which risk factors are associated with the occurrence of vascular events in natives/mestizos living in rural coastal Ecuador. We assessed the cardiovascular health (CVH) status and the presence of the metabolic syndrome in all Atahualpa residents aged 40 years or more with stroke and ischemic heart disease and in randomly selected healthy persons to evaluate differences in the prevalence of such risk factors between patients and controls. A total of 120 persons (24 with stroke or ischemic heart disease and 96 matched controls) were included. A poor CVH status (according to the American Heart Association) was found in 87.5% case-patients and 81.3% controls (P = .464). The metabolic syndrome was present in the same proportion (58.3%) of case-patients and controls. Likewise, both sets of risk factors (poor CVH status and the metabolic syndrome) were equally prevalent among both groups (58.3% versus 49%, P = .501). This case-control study suggests that none of the measured risk factors is associated with the occurrence of vascular events. It is possible that some yet unmeasured risk factors or an unknown genetic predisposition may account for a sizable proportion of stroke and ischemic heart disease occurring in the native/mestizo population of rural coastal Ecuador. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Assessing adherence in the CAPRISA 004 tenofovir gel HIV prevention trial: results of a nested case-control study.

PubMed

MacQueen, Kathleen M; Weaver, Mark A; van Loggerenberg, Francois; Succop, Stacey; Majola, Nelisle; Taylor, Doug; Karim, Quarraisha Abdool; Karim, Salim Abdool

2014-05-01

Adherence undeniably impacts product effectiveness in microbicide trials, but the connection has proven challenging to quantify using routinely collected behavioral data. We explored this relationship using a nested case-control study in the CAPRISA 004 Tenofovir (TFV) gel HIV prevention trial. Detailed 3-month recall data on sex events, condom and gel use were collected from 72 incident cases and 205 uninfected controls. We then assessed how the relationship between self-reported adherence and HIV acquisition differed between the TFV and placebo gel groups, an interaction effect that should exist if effectiveness increases with adherence. The CAPRISA 004 trial determined that randomization to TFV gel was associated with a significant reduction in risk of HIV acquisition. In our nested case-control study, however, we did not observe a meaningful decrease in the relative odds of infection-TFV versus placebo-as self-reported adherence increased. To the contrary, exploratory sub-group analysis of the case-control data identified greater evidence for a protective effect of TFV gel among participants reporting less than 80 % adherence to the protocol-defined regimen (odds ratio (OR) 0.30; 95 % CI 0.11-0.78) than among those reporting ≥ 80 % adherence (Odds Ratio 0.81; 95 % CI 0.34-1.92). The small number of cases may have inhibited our ability to detect the hypothesized interaction between adherence and effectiveness. Nonetheless, our results re-emphasize the challenges faced by investigators when adherence may be miss-measured, miss-reported, or confounded with the risk of HIV.

Improvement of individual camouflage through background choice in ground-nesting birds.

PubMed

Stevens, Martin; Troscianko, Jolyon; Wilson-Aggarwal, Jared K; Spottiswoode, Claire N

2017-09-01

Animal camouflage is a longstanding example of adaptation. Much research has tested how camouflage prevents detection and recognition, largely focusing on changes to an animal's own appearance over evolution. However, animals could also substantially alter their camouflage by behaviourally choosing appropriate substrates. Recent studies suggest that individuals from several animal taxa could select backgrounds or positions to improve concealment. Here, we test whether individual wild animals choose backgrounds in complex environments, and whether this improves camouflage against predator vision. We studied nest site selection by nine species of ground-nesting birds (nightjars, plovers and coursers) in Zambia, and used image analysis and vision modeling to quantify egg and plumage camouflage to predator vision. Individual birds chose backgrounds that enhanced their camouflage, being better matched to their chosen backgrounds than to other potential backgrounds with respect to multiple aspects of camouflage. This occurred at all three spatial scales tested (a few cm and five meters from the nest, and compared to other sites chosen by conspecifics), and was the case for the eggs of all bird groups studied, and for adult nightjar plumage. Thus, individual wild animals improve their camouflage through active background choice, with choices highly refined across multiple spatial scales.

Improvement of individual camouflage through background choice in ground-nesting birds

PubMed Central

Stevens, Martin; Troscianko, Jolyon; Wilson-Aggarwal, Jared K.; Spottiswoode, Claire N.

2017-01-01

Animal camouflage is a longstanding example of adaptation. Much research has tested how camouflage prevents detection and recognition, largely focusing on changes to an animal's own appearance over evolution. However, animals could also substantially alter their camouflage by behaviourally choosing appropriate substrates. Recent studies suggest that individuals from several animal taxa could select backgrounds or positions to improve concealment. Here, we test whether individual wild animals choose backgrounds in complex environments, and whether this improves camouflage against predator vision. We studied nest site selection by nine species of ground-nesting birds (nightjars, plovers and coursers) in Zambia, and used image analysis and vision modeling to quantify egg and plumage camouflage to predator vision. Individual birds chose backgrounds that enhanced their camouflage, being better matched to their chosen backgrounds than to other potential backgrounds with respect to multiple aspects of camouflage. This occurred at all three spatial scales tested (a few cm and five meters from the nest, and compared to other sites chosen by conspecifics), and was the case for the eggs of all bird groups studied, and for adult nightjar plumage. Thus, individual wild animals improve their camouflage through active background choice, with choices highly refined across multiple spatial scales. PMID:28890937

Acrylamide and glycidamide hemoglobin adducts and epithelial ovarian cancer: a nested case-control study in non-smoking postmenopausal women from the EPIC cohort

PubMed Central

Obón-Santacana, Mireia; Lujan-Barroso, Leila; Travis, Ruth C.; Freisling, Heinz; Ferrari, Pietro; Severi, Gianluca; Baglietto, Laura; Boutron-Ruault, Marie-Christine; Fortner, Renée T.; Ose, Jennifer; Boeing, Heiner; Menéndez, Virginia; Sánchez-Cantalejo, Emilio; Chamosa, Saioa; Huerta Castaño, José María; Ardanaz, Eva; Khaw, Kay-Tee; Wareham, Nick; Merritt, Melissa A.; Gunter, Marc J.; Trichopoulou, Antonia; Papatesta, Eleni-Maria; Klinaki, Eleni; Saieva, Calogero; Tagliabue, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Bueno-de-Mesquita, H.B.; Peeters, Petra H.; Onland-Moret, N. Charlotte; Idahl, Annika; Lundin, Eva; Weiderpass, Elisabete; Vesper, Hubert W.; Riboli, Elio; Duell, Eric J

2015-01-01

Background Acrylamide was classified as ‘probably carcinogenic to humans (group 2A)’ by the International Agency for Research on Cancer. Epithelial ovarian cancer (EOC) is the fourth cause of cancer mortality in women. Five epidemiological studies have evaluated the association between EOC risk and dietary acrylamide intake assessed using food frequency questionnaires, and one nested case-control study evaluated hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) and EOC risk; the results of these studies were inconsistent. Methods A nested case-control study in non-smoking postmenopausal women (334 cases, 417 controls) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Unconditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA and EOC and invasive serous EOC risk. Results No overall associations were observed between biomarkers of acrylamide exposure analyzed in quintiles and EOC risk; however, positive associations were observed between some middle quintiles of HbGA and HbAA+HbGA. Elevated but non-statistically significant ORs for serous EOC were observed for HbGA and HbAA+HbGA (ORQ5vsQ1:1.91, 95%CI:0.96-3.81 and ORQ5vsQ1:1.90, 95%CI:0.94-3.83, respectively); however, no linear dose-response trends were observed. Conclusion This EPIC nested case-control study failed to observe a clear association between biomarkers of acrylamide exposure and the risk of EOC or invasive serous EOC. Impact It is unlikely that dietary acrylamide exposure increases ovarian cancer risk; however, additional studies with larger sample size should be performed to exclude any possible association with EOC risk. PMID:26376083

Altered Growth Trajectory of Head Circumference During Infancy and Schizophrenia in a National Birth Cohort

PubMed Central

Brown, Alan S.; Gyllenberg, David; Hinkka-Yli-Salomäki, Susanna; Sourander, Andre; McKeague, Ian W.

2016-01-01

Identification of abnormalities in the developmental trajectory during infancy of future schizophrenia cases offers the potential to reveal pathogenic mechanisms of this disorder. Previous studies of head circumference in pre-schizophrenia were limited to measures at birth. The use of growth acceleration of head circumference (defined as the rate of change in head circumference) provides a more informative representation of the maturational landscape of this measure compared to studies based on static head circumference measures. To date, however, no study has examined whether HC growth acceleration differs between pre-schizophrenia cases and controls. In the present study, we employed a nested case control design of a national birth cohort in Finland. Cases with schizophrenia or schizoaffective disorder (N=375) and controls (N=375) drawn from the birth cohort were matched 1:1 on date of birth (within 1 month), sex, and residence in Finland at case diagnosis. Longitudinal data were obtained on head circumference from birth through age 1. Data were analyzed using a new nonparametric Bayesian inversion method which allows for a detailed understanding of growth dynamics. Adjusting for growth velocity of height and weight, and gestational age, there was significantly accelerated growth of head circumference in females with schizophrenia from birth to 2 months; the findings remained significant following Bonferroni correction (p < 0.0125). This is the first study to report abnormal HC growth acceleration, a more sensitive measure of somatic developmental deviation of this measure, in schizophrenia. PMID:27818077

Urine phyto-oestrogen metabolites are not significantly associated with risk of type 2 diabetes: the Singapore Chinese health study.

PubMed

Talaei, Mohammad; Lee, Bee L; Ong, Choon N; van Dam, Rob M; Yuan, Jian M; Koh, Woon P; Pan, An

2016-05-01

We evaluated the relationship between urine concentrations of phyto-oestrogens (isoflavones and lignans) and risk of incident type 2 diabetes in middle-aged and elderly Chinese residing in Singapore. Urine metabolites of isoflavones and lignans were assayed by HPLC among 564 diabetes cases and 564 matched controls in a case-control study nested within the Singapore Chinese Health Study cohort. Participants were free of diagnosed diabetes, CVD and cancer at morning urine collections during 1999-2004. Cases were participants who reported to have physician-diagnosed diabetes at follow-up visits during 2006-2010, whereas controls were randomly selected among those who remained free of diabetes and were matched to the index cases by age, sex, dialect group and date of urine collection. Conditional logistic regression models were used to calculate OR and 95 % CI with adjustment for potential confounders. The mean age of the participants at the time of urine collection was 59·8 years, and the average interval between urine collection and diabetes diagnosis was 4·0 years. The multivariate-adjusted OR for diabetes were 1·00 (reference), 0·76 (95 % CI 0·52, 1·11), 0·78 (95 % CI 0·53, 1·14) and 0·79 (95 % CI 0·54, 1·15) across quartiles of urine isoflavones (P for trend=0·54), and were 1·00 (reference), 0·87 (95 % CI 0·60, 1·27), 1·10 (95 % CI 0·77, 1·56) and 0·93 (95 % CI 0·63, 1·37) for lignans (P for trend=0·93). The results were similar in men and women, as well as for individual metabolites of isoflavones (genistein, daidzein, glycitin and equol) or lignans (enterodiol and enterolactone). The present study did not find a significant association between urine phyto-oestrogen metabolites and risk of type 2 diabetes in Chinese adults.

HIV infection among U.S. Army and Air Force military personnel: sociodemographic and genotyping analysis.

PubMed

Singer, Darrell E; Bautista, Christian T; O'Connell, Robert J; Sanders-Buell, Eric; Agan, Brian K; Kijak, Gustavo H; Hakre, Shilpa; Sanchez, Jose L; Sateren, Warren B; McCutchan, Francine E; Michael, Nelson L; Scott, Paul T

2010-08-01

Since 1985, the U.S. Department of Defense has periodically screened all military personnel for HIV allowing for the monitoring of the infection in this dynamic cohort population. A nested case-control study was performed to study sociodemographics, overseas assignment, and molecular analysis of HIV. Cases were newly identified HIV infections among U.S. Army and Air Force military personnel from 2000 to 2004. Controls were frequency matched to cases by gender and date of case first positive HIV screening test. Genotyping analysis was performed using high-throughput screening assays and partial genome sequencing. HIV was significantly associated with black race [odds ratio (OR) = 6.65], single marital status (OR = 4.45), and age (OR per year = 1.07). Ninety-seven percent were subtype B and 3% were non-B subtypes (A3, CRF01_AE, A/C recombinant, G, CRF02_AG). Among cases, overseas assignment in the period at risk prior to their first HIV-positive test was associated with non-B HIV subtype infection (OR = 8.44). Black and single military personnel remain disproportionately affected by HIV infection. Most non-B HIV subtypes were associated with overseas assignment. Given the increased frequency and length of assignments, and the expanding HIV genetic diversity observed in this population, there is a need for active HIV genotyping surveillance and a need to reinforce primary HIV prevention efforts.

Factors influencing attempted and completed suicide in postnatal women: A population-based study in Taiwan.

PubMed

Weng, Shu-Chuan; Chang, Jung-Chen; Yeh, Ming-Kung; Wang, Shun-Mu; Chen, Yi-Hua

2016-05-12

The aims of study were to investigate risk factors associated with attempted and completed suicide. This nested case-control study was conducted using the medical and death data of nearly all pregnant women for the period 2002-2012 in Taiwan. A total of 139 cases of attempted suicide and 95 cases of completed suicide were identified; for each case, 10 controls were randomly selected and matched to the cases according to age and year of delivery. A conditional logistic regression model was used. The mean attempted and completed suicide rates were 9.91 and 6.86 per 100,000 women with live births, respectively. Never having married and postpartum depression also increased the risk of attempted suicide (OR = 2.06; 95% CI = 1.09-3.88 and OR = 2.51; 95% CI = 1.10-5.75, respectively) and completed suicide (OR = 20.27; 95% CI = 8.99-45.73 and OR = 21.72; 95% CI = 8.08-58.37, respectively). Other factors for attempted suicide included being widowed or divorced, and having a caesarean delivery or suicide history. Other factors for completed suicide included lower education level, low infant birth weight, and diagnosis of anxiety or mood disorder. These results suggest that people should appropriately assess potential risk factors and provide assistance for postnatal women to reduce the occurrence of suicide events.

The relationship between MnSOD Val16Ala gene polymorphism and the level of serum total antioxidant capacity with the risk of chronic kidney disease in type 2 diabetic patients: a nested case-control study in the Tehran lipid glucose study.

PubMed

Abbasi, Mehrnaz; Daneshpour, Maryam S; Hedayati, Mehdi; Mottaghi, Azadeh; Pourvali, Katayoun; Azizi, Fereidoun

2018-01-01

Several studies have shown significant associations between manganese superoxide dismutase (MnSOD) Val16Ala polymorphism and diabetic complications, but this association has not been explored in relation with chronic kidney disease (CKD) in Type 2 diabetes mellitus (T2DM) patients. Total antioxidant capacity (TAC) level changes in diabetic condition and may play important role in onset or progression of the disease and its complications. The present study investigated the association of MnSOD Val16Ala polymorphism and serum TAC with the risk of CKD in T2DM patients. This nested case-control study included 280 type 2 diabetic patients with CKD and 280 age, sex and diabetes duration-matched control subjects selected from the participants of the Tehran Lipid and Glucose Study. MnSOD val16Ala (rs4880) SNP was genotyped by the Tetra-Primer ARMS-polymerase chain reaction analysis. Serum TAC was measured using ferric-reducing antioxidant power assay. Statistical analysis was performed using STATA statistical package v.12.0 or SPSS (Version 22.0). The Ala allele of the MnSOD Val16Ala polymorphism was associated with a lower risk of CKD (odds ratio (OR), 0.55; 95% confidence interval (CI), 0.36-0.84; P  = 0.006). Median serum TAC in CKD group was 920 μmol/L and was significantly lower ( p  < 0.001) compared to the control group (1045 μmol/L). Using an adjusted conditional logistic regression, we didn't observe any significant interaction between MnSOD Val16Ala SNP with quartiles of serum TAC in relation to CKD. A significant association was found between the MnSOD Val16Ala polymorphism and CKD, but this association is not affected by serum TAC level in T2DM patients.

The ANDROMEDA prospective cohort study: predictive value of combined criteria to tailor breast cancer screening and new opportunities from circulating markers: study protocol.

PubMed

Giordano, Livia; Gallo, Federica; Petracci, Elisabetta; Chiorino, Giovanna; Segnan, Nereo

2017-11-22

In recent years growing interest has been posed on alternative ways to screen women for breast cancer involving different imaging techniques or adjusting screening interval by breast cancer risk estimates. A new research area is studying circulating microRNAs as molecular biomarkers potentially useful for non invasive early detection together with the analysis of single-nucleotide polymorphisms (SNPs). The Andromeda study is a prospective cohort study on women attending breast cancer screening in a northern Italian area. The aims of the study are: 1) to define appropriate women risk-based stratifications for personalized screening considering different factors (reproductive, family and biopsy history, breast density, lifestyle habits); 2) to evaluate the diagnostic accuracy of selected circulating microRNAs in a case-control study nested within the above mentioned cohort. About 21,000 women aged 46-67 years compliant to screening mammography are expected to be enrolled. At enrolment, information on well-known breast cancer risk factors and life-styles habits are collected through self-admistered questionnaires. Information on breast density and anthropometric measurements (height, weight, body composition, and waist circumference) are recorded. In addition, women are requested to provide a blood sample for serum, plasma and buffy-coat storing for subsequent molecular analyses within the nested case-control study. This investigation will be performed on approximately 233 cases (screen-detected) and 699 matched controls to evaluate SNPs and circulating microRNAs. The whole study will last three years and the cohort will be followed up for ten years to observe the onset of new breast cancer cases. Nowadays women undergo the same screening protocol, independently of their breast density and their individual risk to develop breast cancer. New criteria to better stratify women in risk groups could enable the screening strategies to target high-risk women while reducing interventions in those at low-risk. In this frame the present study will contribute in identifying the feasibility and impact of implementing personalized breast cancer screening. NCT02618538 (retrospectively registered on 27-11-2015.).

OPG and sRANKL serum levels and incident hip fracture in postmenopausal Caucasian women in the Women's Health Initiative Observational Study

PubMed Central

LaCroix, Andrea Z.; Jackson, Rebecca D.; Aragaki, Aaron; Kooperberg, Charles; Cauley, Jane A.; Chen, Zhao; LeBoff, Meryl S.; Duggan, David; Wactawski-Wende, Jean

2013-01-01

Purpose The osteoprotogerin/receptor activator of NF-kappa β/receptor activator of NF-kappa β ligand (OPG/RANK/RANKL) pathway plays a critical role in bone remodeling. This study investigated associations between serum levels of OPG, soluble RANKL (sRANKL), and the ratio of OPG/sRANKL to risk of incident hip fracture. Methods A nested case–control study was conducted among postmenopausal, Caucasian women aged 50–79 at baseline (1993–1998), followed for hip fracture through March 2005 in the Women's Health Initiative Observational Study. 400 incident hip fracture cases were selected and individually matched to 400 controls with noprior fracture or incident hip fracture. Matching factors were baseline age, enrollment date and hormone therapy (HT) exposure. Baseline serum OPG and sRANKL levels were measured using high sensitivity ELISA. Odds ratios were computed for quartiles of each biomarker adjusting for matching factors and hip fracture risk factors. Results Serum OPG was significantly associated with older age, low physical activity and poorer physical function in control women. sRANKL was inversely associated with total calcium intake in control women, but not associated with age or other fracture risk factors. The odds ratio for hip fracture comparing the highest to lowest quartiles of OPG was 2.28 (95% confidence interval (CI), 1.45–3.61) after adjusting for the matching variables (p-value for linear trend <0.001), and 1.87 (95% CI, 1.15–3.04; p for linear trend = 0.02) after adjusting for self-rated health status, physical activity and physical functioning. No significant associations between sRANKL or the ratio of OPG/sRANKL and hip fracture risk were observed. Conclusion Serum OPG levels were independently associated with a nearly twofold increased risk of hip fracture in postmenopausal women. PMID:23735608

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.

Social and economic inequalities in fatal opioid and cocaine related overdoses in Luxembourg: a case-control study.

PubMed

Origer, Alain; Le Bihan, Etienne; Baumann, Michèle

2014-09-01

To investigate social and economic inequalities in fatal overdose cases related to opioid and cocaine use, recorded in Luxembourg between 1994 and 2011. Cross-examination of national data from law enforcement and drug use surveillance sources and of forensic evidence in a nested case-control study design. Overdose cases were individually matched with four controls, when available, according to sex, year of birth, drug administration route and duration of drug use. 272 cases vs 1056 controls were analysed. Conditional logistic regression analysis was performed to assess the respective impact of a series of socioeconomic variables. Being professionally active [OR=0.66 (95% CI 0.45-0.99)], reporting salary as main legal income source [OR=0.42 (95% CI 0.26-0.67)] and education attainment higher than primary school [OR=0.50 (95% CI 0.34-0.73)] revealed to be protective factors, whereas the professional status of the father or legal guardian of victims was not significantly associated to fatal overdoses. Socioeconomic inequalities in drug users impact on the occurrence of fatal overdoses. Compared to their peers, users of illicit drugs with lower socioeconomic profiles show increased odds of dying from overdose. However, actual and self-referred socioeconomic characteristics of drug users, such as educational attainment and employment, may have a greater predictive value of overdose mortality than the parental socioeconomic status. Education, vocational training and socio-professional reintegration should be part of drug-related mortality prevention policies. Copyright © 2014 Elsevier B.V. All rights reserved.

Neonatal hyperbilirubinemia and risk of autism spectrum disorders.

PubMed

Croen, Lisa A; Yoshida, Cathleen K; Odouli, Roxana; Newman, Thomas B

2005-02-01

To investigate the association between neonatal hyperbilirubinemia and autism spectrum disorders (ASD). We conducted a large case-control study nested within the cohort of singleton term infants born between 1995 and 1998 at a northern California Kaiser Permanente hospital. Case subjects (n = 338) were children with an ASD diagnosis recorded in Kaiser Permanente outpatient databases; control subjects (n = 1817) were children without an ASD diagnosis, who were randomly sampled and frequency-matched to case subjects according to gender, birth year, and birth hospital. Approximately 28% of case and control subjects received > or =1 bilirubin test in the first 30 days of life. No case-control differences were observed for maximal bilirubin levels of > or =15 mg/dL (10.1% vs 12.1%), > or =20 mg/dL (2.1% vs 2.5%), or > or =25 mg/dL (0.3% vs 0.2%). Compared with children whose maximal neonatal bilirubin levels were <15 mg/dL or not measured, children with any degree of bilirubin level elevation were not at increased risk of ASD, after adjustment for gender, birth facility, maternal age, maternal race/ethnicity, maternal education, and gestational age (for bilirubin levels of 15-19.9 mg/dL: odds ratio: 0.7; 95% confidence interval: 0.5-1.2; for bilirubin levels of 20-24.9 mg/dL: odds ratio: 0.7; 95% confidence interval: 0.3-1.6; for bilirubin levels of > or =25 mg/dL: odds ratio: 1.1; 95% confidence interval: 0.1-11.2). These data suggest that neonatal hyperbilirubinemia is not a risk factor for ASD.

Increased urine semaphorin-3A is associated with renal damage in hypertensive patients with chronic kidney disease: a nested case-control study.

PubMed

Viazzi, Francesca; Ramesh, Ganesan; Jayakumar, Calpurnia; Leoncini, Giovanna; Garneri, Debora; Pontremoli, Roberto

2015-06-01

Semaphorins are guidance proteins implicated in several processes such as angiogenesis, organogenesis, cell migration, and cytokine release. Experimental studies showed that semaphorin-3a (SEMA3A) administration induces transient massive proteinuria, podocyte foot process effacement and endothelial cell damage in healthy animals. While SEMA3A signaling has been demonstrated to be mechanistically involved in experimental diabetic glomerulopathy and in acute kidney injury, to date its role in human chronic kidney disease (CKD) has not been investigated. To test the hypothesis that SEMA3A may play a role in human CKD, we performed a cross-sectional, nested, case-control study on 151 matched hypertensive patients with and without CKD. SEMA3A was quantified in the urine (USEMA) by ELISA. Glomerular filtration rate was estimated (eGFR) by the CKD-EPI formula and albuminuria was measured as albumin-to-creatinine ratio (ACR). USEMA levels were positively correlated with urine ACR (p = 0.001) and serum creatinine (p < 0.001). USEMA was higher in patients with both components of renal damage as compared to those with only one and those with normal renal function (p < 0.007 and <0.001, respectively). The presence of increased USEMA levels (i.e. top quartile) entailed a fourfold higher risk of combined renal damage (p < 0.001) and an almost twofold higher risk of macroalbuminuria (p = 0.005) or of reduced eGFR, even adjusting for confounding factors (p = 0.002). USEMA is independently associated with CKD in both diabetic and non diabetic hypertensive patients. Further studies may help clarify the mechanisms underlying this association and possibly the pathogenic changes leading to the development of CKD.

Using ancestry matching to combine family-based and unrelated samples for genome-wide association studies‡

PubMed Central

Crossett, Andrew; Kent, Brian P.; Klei, Lambertus; Ringquist, Steven; Trucco, Massimo; Roeder, Kathryn; Devlin, Bernie

2015-01-01

We propose a method to analyze family-based samples together with unrelated cases and controls. The method builds on the idea of matched case–control analysis using conditional logistic regression (CLR). For each trio within the family, a case (the proband) and matched pseudo-controls are constructed, based upon the transmitted and untransmitted alleles. Unrelated controls, matched by genetic ancestry, supplement the sample of pseudo-controls; likewise unrelated cases are also paired with genetically matched controls. Within each matched stratum, the case genotype is contrasted with control pseudo-control genotypes via CLR, using a method we call matched-CLR (mCLR). Eigenanalysis of numerous SNP genotypes provides a tool for mapping genetic ancestry. The result of such an analysis can be thought of as a multidimensional map, or eigenmap, in which the relative genetic similarities and differences amongst individuals is encoded in the map. Once constructed, new individuals can be projected onto the ancestry map based on their genotypes. Successful differentiation of individuals of distinct ancestry depends on having a diverse, yet representative sample from which to construct the ancestry map. Once samples are well-matched, mCLR yields comparable power to competing methods while ensuring excellent control over Type I error. PMID:20862653

Effects of schistosomiasis on susceptibility to HIV-1 infection and HIV-1 viral load at HIV-1 seroconversion: A nested case-control study.

PubMed

Downs, Jennifer A; Dupnik, Kathryn M; van Dam, Govert J; Urassa, Mark; Lutonja, Peter; Kornelis, Dieuwke; de Dood, Claudia J; Hoekstra, Pytsje; Kanjala, Chifundo; Isingo, Raphael; Peck, Robert N; Lee, Myung Hee; Corstjens, Paul L A M; Todd, Jim; Changalucha, John M; Johnson, Warren D; Fitzgerald, Daniel W

2017-09-01

Schistosomiasis affects 218 million people worldwide, with most infections in Africa. Prevalence studies suggest that people with chronic schistosomiasis may have higher risk of HIV-1 acquisition and impaired ability to control HIV-1 replication once infected. We hypothesized that: (1) pre-existing schistosome infection may increase the odds of HIV-1 acquisition and that the effects may differ between men and women, and (2) individuals with active schistosome infection at the time of HIV-1 acquisition may have impaired immune control of HIV-1, resulting in higher HIV-1 viral loads at HIV-1 seroconversion. We conducted a nested case-control study within a large population-based survey of HIV-1 transmission in Tanzania. A population of adults from seven villages was tested for HIV in 2007, 2010, and 2013 and dried blood spots were archived for future studies with participants' consent. Approximately 40% of this population has Schistosoma mansoni infection, and 2% has S. haematobium. We tested for schistosome antigens in the pre- and post-HIV-1-seroconversion blood spots of people who acquired HIV-1. We also tested blood spots of matched controls who did not acquire HIV-1 and calculated the odds that a person with schistosomiasis would become HIV-1-infected compared to these matched controls. Analysis was stratified by gender. We compared 73 HIV-1 seroconverters with 265 controls. Women with schistosome infections had a higher odds of HIV-1 acquisition than those without (adjusted OR = 2.8 [1.2-6.6], p = 0.019). Schistosome-infected men did not have an increased odds of HIV-1 acquisition (adjusted OR = 0.7 [0.3-1.8], p = 0.42). We additionally compared HIV-1 RNA levels in the post-seroconversion blood spots in HIV-1 seroconverters with schistosomiasis versus those without who became HIV-infected in 2010, before antiretroviral therapy was widely available in the region. The median whole blood HIV-1 RNA level in the 15 HIV-1 seroconverters with schistosome infection was significantly higher than in the 22 without schistosomiasis: 4.4 [3.9-4.6] log10 copies/mL versus 3.7 [3.2-4.3], p = 0.017. We confirm, in an area with endemic S. mansoni, that pre-existing schistosome infection increases odds of HIV-1 acquisition in women and raises HIV-1 viral load at the time of HIV-1 seroconversion. This is the first study to demonstrate the effect of schistosome infection on HIV-1 susceptibility and viral control, and to differentiate effects by gender. Validation studies will be needed at additional sites.

The use of a metronome during cardiopulmonary resuscitation in the emergency room of a university hospital

PubMed Central

Botelho, Renata Maria de Oliveira; Campanharo, Cássia Regina Vancini; Lopes, Maria Carolina Barbosa Teixeira; Okuno, Meiry Fernanda Pinto; de Góis, Aécio Flávio Teixeira; Batista, Ruth Ester Assayag

2016-01-01

ABSTRACT Objective: to compare the rate of return of spontaneous circulation (ROSC) and death after cardiac arrest, with and without the use of a metronome during cardiopulmonary resuscitation (CPR). Method: case-control study nested in a cohort study including 285 adults who experienced cardiac arrest and received CPR in an emergency service. Data were collected using In-hospital Utstein Style. The control group (n=60) was selected by matching patients considering their neurological condition before cardiac arrest, the immediate cause, initial arrest rhythm, whether epinephrine was used, and the duration of CPR. The case group (n=51) received conventional CPR guided by a metronome set at 110 beats/min. Chi-square and likelihood ratio were used to compare ROSC rates considering p≤0.05. Results: ROSC occurred in 57.7% of the cases, though 92.8% of these patients died in the following 24 hours. No statistically significant difference was found between groups in regard to ROSC (p=0.2017) or the occurrence of death (p=0.8112). Conclusion: the outcomes of patients after cardiac arrest with and without the use of a metronome during CPR were similar and no differences were found between groups in regard to survival rates and ROSC. PMID:27878221

Suicide risk and antipsychotic side effects in schizophrenia: nested case-control study.

PubMed

Reutfors, Johan; Clapham, Eric; Bahmanyar, Shahram; Brandt, Lena; Jönsson, Erik G; Ekbom, Anders; Bodén, Robert; Ösby, Urban

2016-07-01

This study explores suicide risk in schizophrenia in relation to side effects from antipsychotic medication. Among patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n = 4000), those who died by suicide within 5 years from diagnosis were defined as cases (n = 84; 54% male). For each case, one individually matched control was identified from the same population. Information on antipsychotic side effects, including extrapyramidal symptoms (EPS) and akathisia, as well as prescriptions of anticholinergic medication, was retrieved from clinical records in a blinded fashion. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of the association between suicide and side effects as well as anticholinergic medication were estimated using conditional logistic regression. A lower suicide risk was found in patients with a history of EPS (aOR 0.33, 95% CI 0.12-0.94). There was no statistically significant association between akathisia or anticholinergic medication use and the suicide risk. A lower suicide risk identified among patients with EPS could potentially reflect higher antipsychotic adherence, exposure to higher dosage, or polypharmacy among these patients. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Risk of treatment-related esophageal cancer among breast cancer survivors.

PubMed

Morton, L M; Gilbert, E S; Hall, P; Andersson, M; Joensuu, H; Vaalavirta, L; Dores, G M; Stovall, M; Holowaty, E J; Lynch, C F; Curtis, R E; Smith, S A; Kleinerman, R A; Kaijser, M; Storm, H H; Pukkala, E; Weathers, R E; Linet, M S; Rajaraman, P; Fraumeni, J F; Brown, L M; van Leeuwen, F E; Fossa, S D; Johannesen, T B; Langmark, F; Lamart, S; Travis, L B; Aleman, B M P

2012-12-01

Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use. Nested case-control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records. The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (P(trend )< 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7-28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2-0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking). Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up.

Clonal haemopoiesis and therapy-related myeloid malignancies in elderly patients: a proof-of-concept, case-control study.

PubMed

Gillis, Nancy K; Ball, Markus; Zhang, Qing; Ma, Zhenjun; Zhao, YuLong; Yoder, Sean J; Balasis, Maria E; Mesa, Tania E; Sallman, David A; Lancet, Jeffrey E; Komrokji, Rami S; List, Alan F; McLeod, Howard L; Alsina, Melissa; Baz, Rachid; Shain, Kenneth H; Rollison, Dana E; Padron, Eric

2017-01-01

Clonal haemopoiesis of indeterminate potential (CHIP) is an age-associated genetic event linked to increased risk of primary haematological malignancies and increased all-cause mortality, but the prevalence of CHIP in patients who develop therapy-related myeloid neoplasms is unknown. We did this study to investigate whether chemotherapy-treated patients with cancer who have CHIP are at increased risk of developing therapy-related myeloid neoplasms. We did a nested, case-control, proof-of-concept study to compare the prevalence of CHIP between patients with cancer who later developed therapy-related myeloid neoplasms (cases) and patients who did not develop these neoplasms (controls). We identified cases from our internal biorepository of 123 357 patients who consented to participate in the Total Cancer Care biobanking protocol at Moffitt Cancer Center (Tampa, FL, USA) between Jan 1, 2006, and June 1, 2016. We included all individuals who were diagnosed with a primary malignancy, were treated with chemotherapy, subsequently developed a therapy-related myeloid neoplasm, and were 70 years or older at either diagnosis. For inclusion in this study, individuals must have had a peripheral blood or mononuclear cell sample collected before the diagnosis of therapy-related myeloid neoplasm. Controls were individuals who were diagnosed with a primary malignancy at age 70 years or older and were treated with chemotherapy but did not develop therapy-related myeloid neoplasms. Controls were matched to cases in at least a 4:1 ratio on the basis of sex, primary tumour type, age at diagnosis, smoking status, chemotherapy drug class, and duration of follow-up. We used sequential targeted and whole-exome sequencing and described clonal evolution in cases for whom paired CHIP and therapy-related myeloid neoplasm samples were available. The primary endpoint of this study was the development of therapy-related myeloid neoplasm and the primary exposure was CHIP. We identified 13 cases and 56 case-matched controls. The prevalence of CHIP in all patients (23 [33%] of 69 patients) was higher than has previously been reported in elderly individuals without cancer (about 10%). Cases had a significantly higher prevalence of CHIP than did matched controls (eight [62%] of 13 cases vs 15 [27%] of 56 controls, p=0·024; odds ratio 5·75, 95% CI 1·52-25·09, p=0·013). The most commonly mutated genes in cases with CHIP were TET2 (three [38%] of eight patients) and TP53(three [38%] of eight patients), whereas controls most often had TET2 mutations (six [40%] of 15 patients). In most (four [67%] of six patients) cases for whom paired CHIP and therapy-related myeloid neoplasm samples were available, the mean allele frequency of CHIP mutations had expanded by the time of the therapy-related myeloid neoplasm diagnosis. However, a subset of paired samples (two [33%] of six patients) had CHIP mutations that decreased in allele frequency, giving way to expansion of a distinct mutant clone. Patients with cancer who have CHIP are at increased risk of developing therapy-related myeloid neoplasms. The distribution of CHIP-related gene mutations differs between individuals with therapy-related myeloid neoplasm and those without, suggesting that mutation-specific differences might exist in therapy-related myeloid neoplasm risk. Moffitt Cancer Center. Copyright © 2017 Elsevier Ltd. All rights reserved.

Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data

PubMed Central

Hernandez, Rohini K

2011-01-01

Objective To compare the risk of non-fatal venous thromboembolism in women receiving oral contraceptives containing drospirenone with that in women receiving oral contraceptives containing levonorgestrel. Design Nested case-control and cohort study. Setting The study was based on information from PharMetrics, a United States based company that collects information on claims paid by managed care plans. Participants The study encompassed all women aged 15 to 44 years who received an oral contraceptive containing either drospirenone or levonorgestrel after 1 January 2002. Cases were women with current use of a study oral contraceptive and a diagnosis of venous thromboembolism in the absence of identifiable clinical risk factors (idiopathic venous thromboembolism). Up to four controls were matched to each case by age and calendar time. Main outcome measures Odds ratios comparing the risk of non-fatal venous thromboembolism in users of the two contraceptives; incidence rates and rate ratios of non-fatal venous thromboembolism for users of each of the study contraceptives. Results 186 newly diagnosed, idiopathic cases of venous thromboembolism were identified in the study population and matched with 681 controls. In the case-control analysis, the conditional odds ratio for venous thromboembolism comparing use of oral contraceptives containing drospirenone with use of those containing levonorgestrel was 2.3 (95% confidence interval 1.6 to 3.2). The incidence rates for venous thromboembolism in the study population were 30.8 (95% confidence interval 25.6 to 36.8) per 100 000 woman years among users of oral contraceptives containing drospirenone and 12.5 (9.61 to 15.9) per 100 000 woman years among users of oral contraceptives containing levonorgestrel. The age adjusted incidence rate ratio for venous thromboembolism for current use of oral contraceptives containing drospirenone compared with those containing levonorgestrel was 2.8 (2.1 to 3.8). Conclusions The risk of non-fatal venous thromboembolism among users of oral contraceptives containing drospirenone seems to be around twice that of users of oral contraceptives containing levonorgestrel, after the effects of potential confounders and prescribing biases have been taken into account. PMID:21511805

A multicenter, case-control study on risk factors for antepartum stillbirth.

PubMed

Facchinetti, Fabio; Alberico, Salvatore; Benedetto, Chiara; Cetin, Irene; Cozzolino, Sabrina; Di Renzo, Gian Carlo; Del Giovane, Cinzia; Ferrari, Francesca; Mecacci, Federico; Menato, Guido; Tranquilli, Andrea L; Baronciani, Dante

2011-03-01

As the influence of socio-demographic variables, lifestyle and medical conditions on the epidemiology of stillbirth (SB) is modified by population features, we aimed at investigating the role played by these factors on the incidence of SB in a developed country. Multivariate logistic regression analysis (OR with 95% CI) was utilized in a prospective multicentre nested case-control study to compare in a 1:2 ratio stillborn of >22 weeks gestation with matched for gestational age live-born (LB) infants. Intrapartum SB were excluded. Two hundred fifty-four consecutive SBs and 497 LBs were enrolled. Socio-demographic variables were equally distributed. Fetal malformations (7.96, 2.69-23.55), severe intrauterine growth restriction (IUGR) (birthweight ≤ 5(th) %ile) (4.32, 2.27?8.24), BMI > 25 (2.87, 1.90-4.33), and preeclampsia (PE, 0.40, 0.21-0.77) were recognized as independent predictors for SB. At term, only BMI > 25 was associated with SB (7.70, 2.9-20.5). Fetal malformations, severe IUGR and maternal BMI > 25 were associated with a significant increase in the risk of SB; PE presented instead a protective role. Maternal BMI > 25 was the only risk factor for SB identified in term pregnancies.

Statistical analysis of donation--transfusion data with complex correlation.

PubMed

Reilly, Marie; Szulkin, Robert

2007-12-30

Blood-borne transmission of disease is estimated from linked data records from blood donors and transfusion recipients. However, such data are characterized by complex correlation due to donors typically contributing many donations and recipients being transfused with multiple units of blood product. In this paper, we present a method for analysing such data, by using a modification of a nested case-control design. For recipients who develop the disease of interest (cases) and their matched controls, all donors who contributed blood to these individuals define clusters or 'families' of related individuals. Using a Cox regression model for the hazard of the individuals within clusters of donors, we estimate the risk of transmission, and a bootstrap step provides valid standard errors provided the clusters are independent. As an illustration, we apply the method to the analysis of a large database of Swedish donor and recipient records linked to the population cancer register. We investigate whether there is an increased risk of cancer in recipients transfused with blood from donors who develop cancer after donating. Our method provides a powerful alternative to the small 'look-back' studies typical of transfusion medicine and can make an important contribution to haemovigilance efforts. Copyright (c) 2007 John Wiley & Sons, Ltd.

Elevated maternal C-reactive protein and increased risk of schizophrenia in a national birth cohort.

PubMed

Canetta, Sarah; Sourander, Andre; Surcel, Heljä-Marja; Hinkka-Yli-Salomäki, Susanna; Leiviskä, Jaana; Kellendonk, Christoph; McKeague, Ian W; Brown, Alan S

2014-09-01

The objective of the present study was to investigate an association between early gestational C-reactive protein, an established inflammatory biomarker, prospectively assayed in maternal sera, and schizophrenia in a large, national birth cohort with an extensive serum biobank. A nested case-control design from the Finnish Prenatal Study of Schizophrenia cohort was utilized. A total of 777 schizophrenia cases (schizophrenia, N=630; schizoaffective disorder, N=147) with maternal sera available for C-reactive protein testing were identified and matched to 777 control subjects in the analysis. Maternal C-reactive protein levels were assessed using a latex immunoassay from archived maternal serum specimens. Increasing maternal C-reactive protein levels, classified as a continuous variable, were significantly associated with schizophrenia in offspring (adjusted odds ratio=1.31, 95% confidence interval=1.10-1.56). This finding remained significant after adjusting for potential confounders, including maternal and parental history of psychiatric disorders, twin/singleton birth, urbanicity, province of birth, and maternal socioeconomic status. This finding provides the most robust evidence to date that maternal inflammation may play a significant role in schizophrenia, with possible implications for identifying preventive strategies and pathogenic mechanisms in schizophrenia and other neurodevelopmental disorders.

Impact of Oxidative Stress Biomarkers and Carboxymethyllysine (An Advanced Glycation End Product) on Prostate Cancer: A Prospective Study

PubMed Central

Yang, Shuman; Pinney, Susan M.; Mallick, Palash; Ho, Shuk-Mei; Bracken, Bruce; Wu, Tianying

2015-01-01

Introduction Biomarkers of oxidative stress and advanced glycation end products (AGE) have been linked to the development of prostate cancer, but evidence from human studies is either scarce or controversial. Materials and Methods We conducted a prospective nested case-control study among 48 men (24 prostate cancer cases and 24 controls) aged 48–76 years at baseline. The participants of our study were a part of the Fernald Community Cohort (FCC). Prostate cancer cases and controls were matched individually on age (± 3 years) with 1:1 ratio. Biomarkers included urine F2-isoprostanes (markers of lipid oxidation), plasma fluorescent oxidation products (FlOPs; markers of global oxidation) and carboxymethyllysine (CML; a major end-stage AGE). Results At baseline, cases had similar age, body mass index, proportion of family history of prostate cancer, history of benign prostatic hyperplasia, history of hypertension, history of diabetes, smokers and plasma glucose levels as compared to controls. Levels of plasma CML were significantly higher in cases than in controls (182 vs. 152 μg/ml, P < 0.05). In the conditional logistic regression model, an increase in CML equivalent to one standard deviation was associated with increased risk of incident prostate cancer (Relative risk = 1.79, 95% confidence interval = 1.00–3.21), and accounted for ~8% variance of prostate cancer liability. Urine F2-isoprostanes and plasma FlOPs were not associated with prostate cancer incidence. Conclusion Higher levels of plasma CML were associated with increased risk of prostate cancer. This suggests a potential new pathway for prostate cancer prediction and treatment. PMID:25972296

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.

Inverse association between cancer and Alzheimer's disease: results from the Framingham Heart Study.

PubMed

Driver, Jane A; Beiser, Alexa; Au, Rhoda; Kreger, Bernard E; Splansky, Greta Lee; Kurth, Tobias; Kiel, Douglas P; Lu, Kun Ping; Seshadri, Sudha; Wolf, Phillip A

2012-03-12

To relate cancer since entry into the Framingham Heart Study with the risk of incident Alzheimer's disease and to estimate the risk of incident cancer among participants with and without Alzheimer's disease. Community based prospective cohort study; nested age and sex matched case-control study. Framingham Heart Study, USA. 1278 participants with and without a history of cancer who were aged 65 or more and free of dementia at baseline (1986-90). Hazard ratios and 95% confidence intervals for the risks of Alzheimer's disease and cancer. Over a mean follow-up of 10 years, 221 cases of probable Alzheimer's disease were diagnosed. Cancer survivors had a lower risk of probable Alzheimer's disease (hazard ratio 0.67, 95% confidence interval 0.47 to 0.97), adjusted for age, sex, and smoking. The risk was lower among survivors of smoking related cancers (0.26, 0.08 to 0.82) than among survivors of non-smoking related cancers (0.82, 0.57 to 1.19). In contrast with their decreased risk of Alzheimer's disease, survivors of smoking related cancer had a substantially increased risk of stroke (2.18, 1.29 to 3.68). In the nested case-control analysis, participants with probable Alzheimer's disease had a lower risk of subsequent cancer (0.39, 0.26 to 0.58) than reference participants, as did participants with any Alzheimer's disease (0.38) and any dementia (0.44). Cancer survivors had a lower risk of Alzheimer's disease than those without cancer, and patients with Alzheimer's disease had a lower risk of incident cancer. The risk of Alzheimer's disease was lowest in survivors of smoking related cancers, and was not primarily explained by survival bias. This pattern for cancer is similar to that seen in Parkinson's disease and suggests an inverse association between cancer and neurodegeneration.

Prenatal toxoplasmosis antibody and childhood autism.

PubMed

Spann, Marisa N; Sourander, Andre; Surcel, Heljä-Marja; Hinkka-Yli-Salomäki, Susanna; Brown, Alan S

2017-05-01

There is evidence that some maternal infections during the prenatal period are associated with neurodevelopmental disorders, such as childhood autism. However, the association between autism and Toxoplasma gondii (T. gondii), an intracellular parasite, remains unclear. The authors examined whether serologically confirmed maternal antibodies to T. gondii are associated with odds of childhood autism in offspring. The study is based on a nested case-control design of a large national birth cohort (N = 1.2 million) and the national psychiatric registries in Finland. There were 874 cases of childhood autism and controls matched 1:1 on date of birth, sex, birthplace and residence in Finland. Maternal sera were prospectively assayed from a national biobank for T. gondii IgM and IgG antibodies; IgG avidity analyses were also performed. High maternal T. gondii IgM antibody was associated with a significantly decreased odds of childhood autism. Low maternal T. gondii IgG antibody was associated with increased offspring odds of autism. In women with high T. gondii IgM antibodies, the IgG avidity was high for both cases and controls, with the exception of three controls. The findings suggest that the relationship between maternal T. gondii antibodies and odds of childhood autism may be related to the immune response to this pathogen or the overall activation of the immune system. Autism Res 2017, 10: 769-777. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Serum 25-hydroxyvitamin D and breast cancer in the military: a case-control study utilizing pre-diagnostic serum.

PubMed

Mohr, Sharif B; Gorham, Edward D; Alcaraz, John E; Kane, Christopher I; Macera, Caroline A; Parsons, J Kellogg; Wingard, Deborah L; Horst, Ronald; Garland, Cedric F

2013-03-01

The objective of this study was to ascertain whether a relationship exists between pre-diagnostic serum levels of 25-hydroxyvitamin D (25(OH)D) and risk of breast cancer in young women. About 600 incident cases of breast cancer were matched to 600 controls as part of a nested case-control study that utilized pre-diagnostic sera. Logistic regression was used to assess the relationship between serum 25(OH)D concentration and breast cancer risk, controlling for race and age. According to the conditional logistic regression for all subjects, odds ratios for breast cancer by quintile of serum 25(OH)D from lowest to highest were 1.2, 1.0, 0.9, 1.1, and 1.0 (reference) (p trend = 0.72). After multivariate regression for subjects whose blood had been collected within 90 days preceding diagnosis, odds ratios for breast cancer by quintile of serum 25(OH)D from lowest to highest were 3.3, 1.9, 1.7, 2.6, and 1.0 (reference) (p trend = 0.09). An inverse association between serum 25(OH)D concentration and risk of breast cancer was not present in the principal analysis, although an inverse association was present in a small subgroup analysis of subjects whose blood had been collected within 90 days preceding diagnosis. Further prospective studies of 25(OH)D and breast cancer risk are needed.

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.

The NEST Dry-Run Mode: Efficient Dynamic Analysis of Neuronal Network Simulation Code.

PubMed

Kunkel, Susanne; Schenck, Wolfram

2017-01-01

NEST is a simulator for spiking neuronal networks that commits to a general purpose approach: It allows for high flexibility in the design of network models, and its applications range from small-scale simulations on laptops to brain-scale simulations on supercomputers. Hence, developers need to test their code for various use cases and ensure that changes to code do not impair scalability. However, running a full set of benchmarks on a supercomputer takes up precious compute-time resources and can entail long queuing times. Here, we present the NEST dry-run mode, which enables comprehensive dynamic code analysis without requiring access to high-performance computing facilities. A dry-run simulation is carried out by a single process, which performs all simulation steps except communication as if it was part of a parallel environment with many processes. We show that measurements of memory usage and runtime of neuronal network simulations closely match the corresponding dry-run data. Furthermore, we demonstrate the successful application of the dry-run mode in the areas of profiling and performance modeling.

The NEST Dry-Run Mode: Efficient Dynamic Analysis of Neuronal Network Simulation Code

PubMed Central

Kunkel, Susanne; Schenck, Wolfram

2017-01-01

NEST is a simulator for spiking neuronal networks that commits to a general purpose approach: It allows for high flexibility in the design of network models, and its applications range from small-scale simulations on laptops to brain-scale simulations on supercomputers. Hence, developers need to test their code for various use cases and ensure that changes to code do not impair scalability. However, running a full set of benchmarks on a supercomputer takes up precious compute-time resources and can entail long queuing times. Here, we present the NEST dry-run mode, which enables comprehensive dynamic code analysis without requiring access to high-performance computing facilities. A dry-run simulation is carried out by a single process, which performs all simulation steps except communication as if it was part of a parallel environment with many processes. We show that measurements of memory usage and runtime of neuronal network simulations closely match the corresponding dry-run data. Furthermore, we demonstrate the successful application of the dry-run mode in the areas of profiling and performance modeling. PMID:28701946

Determinants of stunting at 6, 12, 24 and 60 months and postnatal linear growth in Pakistani children.

PubMed

Saleemi, M A; Ashraf, R N; Mellander, L; Zaman, S

2001-11-01

A "nested" case-control design was used to identify cases from a longitudinally followed cohort of 1236 newborns registered during 1984-1987, living in three socioeconomically different areas. The children had a length <-2SDS (standard deviation scores) at 6, 12, 24 and 60 mo of age using the NCHS reference. The controls were matched for gender, area and month of birth. A logistic regression analysis was used for determining the risk factors for stunting at each age. Postnatal linear growth was also examined in these two groups of children and body size was compared with the NCHS reference and that of upper-middle-class children (n = 240). At 6 mo of age, prematurity and duration of breastfeeding showed a significant association with stunting. At 12 mo, maternal height, birthweight and stunting at 6 mo, while at 24 mo, stunting at 6, 12 and 18 mo were identified as important factors. At 60 mo, no other factors besides previous stunting could be identified. The mean height reached at 60 mo showed a deficit of 6 and 13 cm for the controls and the cases, respectively, compared to the NCHS reference. Twenty-eight percent of the children from the two poor areas who were stunted at 6 mo had improved by 60 mo of age. The risk factors for stunting varied at different ages, relating more to feeding at early ages and to previous stunting, predominantly at higher ages. The linear growth showed that faltering increased with age when cases and controls were treated separately. Recovery from stunting could also be demonstrated.

Assessing health and rehabilitation needs of people with disabilities in Cameroon and India.

PubMed

Mactaggart, Islay; Kuper, Hannah; Murthy, G V S; Sagar, Jayanthi; Oye, Joseph; Polack, Sarah

2016-09-01

To assess the association between disability and serious health problems, and the access and uptake of health and rehabilitation services in Cameroon and India. We undertook a population-based case-control study, nested within a survey in Fundong Health District, North West Cameroon (August-October 2013) and in Mahbubnagar District, Telangana State, India (February-April 2014). Disability was defined as the presence of self-reported difficulties in functioning or clinical impairments. One control without disability was selected per case, matched by age, gender and cluster. Information was collected using structured questionnaires on: socioeconomic status, health, access to health services and rehabilitation. Cases with disability were significantly more likely to report a serious health problem in the last year compared to controls in both India (OR = 3.2, 95% CI 2.1-4.8) and Cameroon (OR = 1.9, 1.4-2.7). The vast majority of people sought care when seriously ill, and this did not vary between cases and controls. Awareness and use of rehabilitation services was extremely low in both Cameroon and India. Further focus is needed to improve awareness of rehabilitation services among people with disabilities in India and Cameroon to ensure that their rights are fulfilled and to achieve the goal of Universal Health Coverage. Implications for Rehabilitation People with and without disabilities equally seek health care in India and Cameroon. However, people with disabilities experience more frequent serious health problems than people without. Extremely few people with disabilities were aware of rehabilitation services despite their existence in the study settings.

Maternal polycystic ovary syndrome and the risk of autism spectrum disorders in the offspring: a population-based nationwide study in Sweden.

PubMed

Kosidou, K; Dalman, C; Widman, L; Arver, S; Lee, B K; Magnusson, C; Gardner, R M

2016-10-01

Although many studies indicate the interplay of genetic and environmental factors in the etiology of autism spectrum disorder (ASD), our limited understanding of the underlying mechanisms hampers the development of effective ways of detecting and preventing the disorder. Recent studies support the hypothesis that prenatal androgen exposure contributes to the development of ASD. This would suggest that maternal polycystic ovary syndrome (PCOS), a condition associated with excess androgens, would increase the risk of ASD in the offspring. We conducted a matched case-control study nested within the total population of Sweden (children aged 4-17 who were born in Sweden from 1984 to 2007). The sample consisted of 23 748 ASD cases and 208 796 controls, matched by birth month and year, sex and region of birth. PCOS and ASD were defined from ICD codes through linkage to health-care registers. Maternal PCOS increased the odds of ASD in the offspring by 59%, after adjustment for confounders (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.34-1.88). The odds of offspring ASD were further increased among mothers with both PCOS and obesity, a condition common to PCOS that is related to more severe hyperandrogenemia (OR 2.13, 95% CI 1.46-3.10). Risk estimates did not differ between sexes. In conclusion, children of women with PCOS appear to have a higher risk of developing ASD. This finding awaits confirmation, and exploration of potentially underlying mechanisms, including the role of sex steroids in the etiology of ASD.

Adverse events with intravitreal injection of vascular endothelial growth factor inhibitors: nested case-control study

PubMed Central

Gill, Sudeep S; Bronskill, Susan E; Paterson, J Michael; Whitehead, Marlo

2012-01-01

Objective To assess the risk of systemic adverse events associated with intravitreal injections of vascular endothelial growth factor inhibiting drugs. Design Population based nested case-control study. Setting Ontario, Canada. Participants 91 378 older adults with a history of physician diagnosed retinal disease identified between 1 April 2006 and 31 March 2011. Cases were 1477 patients admitted to hospital for ischaemic stroke, 2229 admitted for an acute myocardial infarction, 1059 admitted or assessed in an emergency department for venous thromboembolism, and 2623 admitted for congestive heart failure. Event-free controls (at a ratio of 5:1) were matched to cases on the basis of year of birth, sex, history of the outcome in the previous 5 years, and diabetes. Main exposure measure Exposure to vascular endothelial growth factor inhibiting drugs identified within 180 days before the index date. Results After adjustment for potential confounders, participants who had ischaemic stroke, acute myocardial infarction, congestive heart failure, or venous thromboembolism were not more likely than control participants to have been exposed to either bevacizumab (adjusted odds ratios of 0.95 (95% confidence interval 0.68 to 1.34) for ischaemic stroke, 1.04 (0.77 to 1.39) for acute myocardial infarction, 0.81 (0.49 to 1.34) for venous thromboembolism, and 1.21 (0.91 to 1.62) for congestive heart failure) or ranibizumab (adjusted odds ratios 0.87 (0.68 to 1.10) for ischaemic stroke, 0.90 (0.72 to 1.11) for acute myocardial infarction, 0.88 (0.67 to 1.16) for venous thromboembolism, and 0.87 (0.70 to 1.07) for congestive heart failure). Similarly, a secondary analysis of exclusive users of bevacizumab or ranibizumab showed no differences in risk between the two drugs (adjusted odds ratios for bevacizumab relative to ranibizumab of 1.03 (0.67 to 1.60) for ischaemic stroke, 1.23 (0.85 to 1.77) for acute myocardial infarction, 0.92 (0.51 to 1.69) for venous thromboembolism, and 1.35 (0.93 to 1.95) for congestive heart failure). These findings were consistent for all but one outcome in subgroup analyses. Conclusions Intravitreal injections of bevacizumab and ranibizumab were not associated with significant risks of ischaemic stroke, acute myocardial infarction, congestive heart failure, or venous thromboembolism. PMID:22763393

Alcohol consumption and PSA-detected prostate cancer risk—A case-control nested in the ProtecT study

PubMed Central

Zuccolo, Luisa; Lewis, Sarah J; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Smith, George Davey

2013-01-01

Alcohol is an established carcinogen but not an established risk factor for prostate cancer, despite some recent prospective studies suggesting increased risk among heavy drinkers. The aim of this study was to investigate the role of alcohol on prostate-specific antigen (PSA) levels and prostate cancer risk. Two thousand four hundred PSA detected prostate cancer cases and 12,700 controls matched on age and general practice were identified through a case-control study nested in the PSA-testing phase of a large UK-based randomized controlled trial for prostate cancer treatment (ProtecT). Linear and multinomial logistic regression models were used to estimate ratios of geometric means (RGMs) of PSA and relative risk ratios (RRRs) of prostate cancer by stage and grade, with 95% confidence intervals (CIs), associated with weekly alcohol intake and drinking patterns. We found evidence of lower PSA (RGM 0.98, 95% CI: 0.98–0.99) and decreased risk of low Gleason-grade (RRR 0.96; 95%CI 0.93–0.99) but increased risk of high-grade prostate cancer (RRR 1.04; 95%CI 0.99–1.08; pdifference=0.004) per 10 units/week increase in alcohol consumption, not explained by current BMI, blood pressure, comorbidities, or reverse causation. This is the first large population-based study to find evidence of lower PSA levels for increasing alcohol consumption, with potential public health implications for the detection of prostate cancer. Our results also support a modestly higher risk of high-grade disease for heavy drinkers, but require independent replication to establish the nature of the association of alcohol with low-grade disease, preferably in cohorts with a heterogeneous case-mix. What's new? Alcohol is not an established risk factor for prostate cancer; however, the current work suggests that heavy drinking could cause a small increase in risk of the more aggressive forms. If the results are confirmed to be causal, prostate cancer risk will be added to the many long-term health risks of heavy drinking, and public health strategies will then also reduce high-risk, poorer prognosis prostate cancer. The authors also found that heavy drinkers have lower PSA levels, suggesting that heavy alcohol consumption could be used as a marker to identify men in whom some cancers might be missed. PMID:23024014

Acute Maternal Infection and Risk of Pre-Eclampsia: A Population-Based Case-Control Study

PubMed Central

Minassian, Caroline; Thomas, Sara L.; Williams, David J.; Campbell, Oona; Smeeth, Liam

2013-01-01

Background Infection in pregnancy may be involved in the aetiology of pre-eclampsia. However, a clear association between acute maternal infection and pre-eclampsia has not been established. We assessed whether acute urinary tract infection, respiratory tract infection, and antibiotic drug prescriptions in pregnancy (a likely proxy for maternal infection) are associated with an increased risk of pre-eclampsia. Methods and Findings We used a matched nested case-control design and data from the UK General Practice Research Database to examine the association between maternal infection and pre-eclampsia. Primiparous women aged at least 13 years and registered with a participating practice between January 1987 and October 2007 were eligible for inclusion. We selected all cases of pre-eclampsia and a random sample of primiparous women without pre-eclampsia (controls). Cases (n = 1533) were individually matched with up to ten controls (n = 14236) on practice and year of delivery. We calculated odds ratios and 95% confidence intervals for pre-eclampsia comparing women exposed and unexposed to infection using multivariable conditional logistic regression. After adjusting for maternal age, pre-gestational hypertension, diabetes, renal disease and multifetal gestation, the odds of pre-eclampsia were increased in women prescribed antibiotic drugs (adjusted odds ratio 1.28;1.14–1.44) and in women with urinary tract infection (adjusted odds ratio 1.22;1.03–1.45). We found no association with maternal respiratory tract infection (adjusted odds ratio 0.91;0.72–1.16). Further adjustment for maternal smoking and pre-pregnancy body mass index made no difference to our findings. Conclusions Women who acquire a urinary infection during pregnancy, but not those who have a respiratory infection, are at an increased risk of pre-eclampsia. Maternal antibiotic prescriptions are also associated with an increased risk. Further research is required to elucidate the underlying mechanism of this association and to determine whether, among women who acquire infections in pregnancy, prompt treatment or prophylaxis against infection might reduce the risk of pre-eclampsia. PMID:24019891

Plasma Riboflavin and Vitamin B-6, but Not Homocysteine, Folate, or Vitamin B-12, Are Inversely Associated with Breast Cancer Risk in the European Prospective Investigation into Cancer and Nutrition-Varese Cohort.

PubMed

Agnoli, Claudia; Grioni, Sara; Krogh, Vittorio; Pala, Valeria; Allione, Alessandra; Matullo, Giuseppe; Di Gaetano, Cornelia; Tagliabue, Giovanna; Pedraglio, Samuele; Garrone, Giulia; Cancarini, Ilaria; Cavalleri, Adalberto; Sieri, Sabina

2016-06-01

One-carbon metabolism-important for DNA stability and integrity-may play a role in breast carcinogenesis. However, epidemiologic studies addressing this issue have yielded inconsistent results. We prospectively investigated associations between breast cancer and plasma folate, riboflavin, vitamin B-6, vitamin B-12, and homocysteine in women recruited to the Varese (Italy) cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We performed a nested case-control study on women aged 35-65 y at recruitment with a median body mass index of 25.3 kg/m(2) who gave blood samples in 1987-1992 and again in 1993-1998. Breast cancer cases identified by 31 December 2009 were individually matched to controls. RRs of breast cancer (and subtypes defined by hormone receptor status) with 95% CIs were estimated by unconditional logistic regression, controlling for matching factors and breast cancer risk factors. After a median of 14.9 y, 276 breast cancer cases were identified and matched to 276 controls. Increasing plasma vitamin B-6 was associated with decreased risk of overall (RR: 0.78; 95% CI: 0.63, 0.96 for 1-SD increase), premenopausal (RR: 0.66; 95% CI: 0.48, 0.92 for 1-SD increase), estrogen receptor-positive (RR: 0.79; 95% CI: 0.63, 1.00 for 1-SD increase), and progesterone receptor-positive (RR: 0.72; 95% CI: 0.55, 0.95 for 1-SD increase) breast cancers. Increased plasma vitamin B-6 was also associated with decreased breast cancer risk in alcohol consumers (≥7 g/d) compared with consumption of <7 g/d or nonconsumption (RR: 0.71; 95% CI: 0.51, 0.99). High plasma riboflavin was associated with significantly lower risk in premenopausal women (RR: 0.45; 95% CI: 0.21, 0.94; highest compared with the lowest quartile, P trend = 0.021). Plasma homocysteine, folate, and vitamin B-12 were not associated with breast cancer risk. High plasma vitamin B-6 and riboflavin may lower breast cancer risk, especially in premenopausal women. Additional research is necessary to further explore these associations. © 2016 American Society for Nutrition.

What parental characteristics can predict child maltreatment at the Emergency Department? Considering expansion of the Hague Protocol.

PubMed

Diderich, Hester M; Dechesne, Mark; Fekkes, Minne; Verkerk, Paul H; Buitendijk, Simone E; Oudesluys-Murphy, Anne-Marie

2015-08-01

The Hague Protocol considers three parental characteristics of Emergency Department adult patients to identify child abuse: (a) domestic violence, (b) intoxication, and (c) suicide attempt or auto mutilation. This study investigated whether additional parental characteristics could be included to improve the chance of detection. Using a nested case-control design, we compared parents identified as child abusers who were missed by the Protocol with a matched group of nonabusing parents. The parental characteristics used were, among others, all physical injuries possibly resulting from domestic violence, psychological, or mental complaints that might indicate elevated domestic stress levels and the number of Emergency Department visits during the previous year. None of the characteristics were statistically significantly associated with child abuse. The Hague Protocol will not be improved by adding one or more of the characteristics that were investigated.

Propensity score matching for selection of local areas as controls for evaluation of effects of alcohol policies in case series and quasi case-control designs.

PubMed

de Vocht, F; Campbell, R; Brennan, A; Mooney, J; Angus, C; Hickman, M

2016-03-01

Area-level public health interventions can be difficult to evaluate using natural experiments. We describe the use of propensity score matching (PSM) to select control local authority areas (LAU) to evaluate the public health impact of alcohol policies for (1) prospective evaluation of alcohol policies using area-level data, and (2) a novel two-stage quasi case-control design. Ecological. Alcohol-related indicator data (Local Alcohol Profiles for England, PHE Health Profiles and ONS data) were linked at LAU level. Six LAUs (Blackpool, Bradford, Bristol, Ipswich, Islington, and Newcastle-upon-Tyne) as sample intervention or case areas were matched to two control LAUs each using PSM. For the quasi case-control study a second stage was added aimed at obtaining maximum contrast in outcomes based on propensity scores. Matching was evaluated based on average standardized absolute mean differences (ASAM) and variable-specific P-values after matching. The six LAUs were matched to suitable control areas (with ASAM < 0.20, P-values >0.05 indicating good matching) for a prospective evaluation study that sought areas that were similar at baseline in order to assess whether a change in intervention exposure led to a change in the outcome (alcohol related harm). PSM also generated appropriate matches for a quasi case-control study--whereby the contrast in health outcomes between cases and control areas needed to be optimized in order to assess retrospectively whether differences in intervention exposure were associated with the outcome. The use of PSM for area-level alcohol policy evaluation, but also for other public health interventions, will improve the value of these evaluations by objective and quantitative selection of the most appropriate control areas. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell Cancer.

PubMed

Hayes, Richard B; Ahn, Jiyoung; Fan, Xiaozhou; Peters, Brandilyn A; Ma, Yingfei; Yang, Liying; Agalliu, Ilir; Burk, Robert D; Ganly, Ian; Purdue, Mark P; Freedman, Neal D; Gapstur, Susan M; Pei, Zhiheng

2018-03-01

Case-control studies show a possible relationship between oral bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are needed to examine the temporal relationship between oral microbiome and subsequent risk of HNSCC. To prospectively examine associations between the oral microbiome and incident HNSCC. This nested case-control study was carried out in 2 prospective cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC were identified during an average 3.9 years of follow-up. Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline. Oral microbiome composition and specific bacterial abundances were determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome composition and specific taxa abundances were compared for the case group and the control group, using PERMANOVA and negative binomial generalized linear models, respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)-adjusted P-value (q-value) <.10 were considered significant. Incident HNSCC. The study included 58 patient cases from CPS-II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck squamous cell cancer cases and controls were similar with respect to age, sex, and race. Patients in the case group were more often current tobacco smokers, tended to have greater alcohol consumption (among drinkers), and to be positive for oral carriage of papillomavirus-16. Overall microbiome composition was not associated with risk of HNSCC. Greater abundance of genera Corynebacterium (fold change [FC], 0.58; 95% confidence interval [CI], 0.41-0.80; q = .06) and Kingella (FC, 0.63; 95% CI, 0.46-0.86; q = .08) were associated with decreased risk of HNSCC, potentially owing to carcinogen metabolism capacity. These findings were consistent for both cohorts and by cohort follow-up time. The observed relationships tended to be stronger for larynx cancer and for individuals with a history of tobacco use. This study demonstrates that greater oral abundance of commensal Corynebacterium and Kingella is associated with decreased risk of HNSCC, with potential implications for cancer prevention.

Brief Report: Maternal Smoking during Pregnancy and Autism Spectrum Disorders

ERIC Educational Resources Information Center

Lee, Brian K.; Gardner, Renee M.; Dal, Henrik; Svensson, Anna; Galanti, Maria Rosaria; Rai, Dheeraj; Dalman, Christina; Magnusson, Cecilia

2012-01-01

Prenatal exposure to tobacco smoke is suggested as a potential risk factor for autism spectrum disorders (ASD). Previous epidemiological studies of this topic have yielded mixed findings. We performed a case-control study of 3,958 ASD cases and 38,983 controls nested in a large register-based cohort in Sweden. ASD case status was measured using a…

A nested case-control study of polychlorinated biphenyls, organochlorine pesticides, and thyroid cancer in the Janus Serum Bank cohort.

PubMed

Lerro, Catherine C; Jones, Rena R; Langseth, Hilde; Grimsrud, Tom K; Engel, Lawrence S; Sjödin, Andreas; Choo-Wosoba, Hyoyoung; Albert, Paul; Ward, Mary H

2018-04-23

Polychlorinated biphenyls (PCBs) and organochlorine pesticides have been associated with altered thyroid hormone levels in humans, but their relationship with thyroid cancer is unknown. We conducted a nested case-control study of thyroid cancer in the Norwegian Janus Serum Bank cohort using pre-diagnostic blood samples from 1972 to 1985. Incident thyroid cancer (n = 108) was ascertained through 2008. Controls were matched 2:1 by age, date of blood draw, gender, and county. We used gas chromatography/mass spectrometry to quantify 36 PCB congeners and metabolites of pesticides DDT, chlordane, hexachlorocyclohexane, and hexachlorobenzene. PCBs and pesticide metabolites were evaluated individually and summed by degree of chlorination and parent compound, respectively. Odds ratios (OR) and 95% confidence intervals (CI) were computed using conditional logistic regression per specified increase in lipid-adjusted concentration. We additionally stratified analyses by birth cohort (1923-1932, 1933-1942, 1943-1957). Increasing concentration of DDT metabolites (OR per 1000 ng/g = 0.80, 95%CI = 0.66-0.98) was inversely associated with thyroid cancer. Associations for PCBs were null or in inverse direction. We observed interactions for total PCBs, moderately-chlorinated PCBs, and chlordane metabolites with birth cohort (p ≤ 0.04). Among participants born 1943-1957, total PCBs (OR per 100 ng/g = 1.25, 95%CI = 1.00-1.56), moderately-chlorinated PCBs (OR per 100 ng/g = 1.31, 95%CI = 1.01-1.70), and chlordane metabolites (OR per 10 ng/g = 1.78, 95%CI = 1.09-2.93) were positively associated with thyroid cancer. For individuals born before 1943, associations were generally null or in the inverse direction. Emissions of PCBs and OC pesticides varied over time. Different risk patterns by birth cohort suggest the potential importance of timing of exposure in thyroid cancer risk. Further evaluation of these associations is warranted. Published by Elsevier Inc.

Greater retention in care among adolescents on antiretroviral treatment accessing "Teen Club" an adolescent-centred differentiated care model compared with standard of care: a nested case-control study at a tertiary referral hospital in Malawi.

PubMed

MacKenzie, Rachel K; van Lettow, Monique; Gondwe, Chrissie; Nyirongo, James; Singano, Victor; Banda, Victor; Thaulo, Edith; Beyene, Teferi; Agarwal, Mansi; McKenney, Allyson; Hrapcak, Susan; Garone, Daniela; Sodhi, Sumeet K; Chan, Adrienne K

2017-11-01

There are numerous barriers to the care and support of adolescents living with HIV (ALHIV) that makes this population particularly vulnerable to attrition from care, poor adherence and virological failure. In 2010, a Teen Club was established in Zomba Central Hospital (ZCH), Malawi, a tertiary referral HIV clinic. Teen Club provides ALHIV on antiretroviral treatment (ART) with dedicated clinic time, sexual and reproductive health education, peer mentorship, ART refill and support for positive living and treatment adherence. The purpose of this study was to evaluate whether attending Teen Club improves retention in ART care. We conducted a nested case-control study with stratified selection, using programmatic data from 2004 to 2015. Cases (ALHIV not retained in care) and controls (ALHIV retained in care) were matched by ART initiation age group. Patient records were reviewed retrospectively and subjects were followed starting in March 2010, the month in which Teen Club was opened. Follow-up ended at the time patients were no longer considered retained in care or on 31 December 2015. Cases and controls were drawn from a study population of 617 ALHIV. Of those, 302 (48.9%) participated in at least two Teen Club sessions. From the study population, 135 (non-retained) cases and 405 (retained) controls were selected. In multivariable analyses, Teen Club exposure, age at the time of selection and year of ART initiation were independently associated with attrition. ALHIV with no Teen Club exposure were less likely to be retained than those with Teen Club exposure (adjusted odds ratio (aOR) 0.27; 95% CI 0.16, 0.45) when adjusted for sex, ART initiation age, current age, reason for ART initiation and year of ART initiation. ALHIV in the age group 15 to 19 were more likely to have attrition from care than ALHIV in the age group 10 to 14 years of age (aOR 2.14; 95% CI 1.12, 4.11). This study contributes to the limited evidence evaluating the effectiveness of service delivery interventions to support ALHIV within healthcare settings. Prospective evaluation of the Teen Club package with higher methodological quality is required for programmes and governments in low- and middle-income settings to prioritize interventions for ALHIV and determine their cost-effectiveness. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Altered growth trajectory of head circumference during infancy and schizophrenia in a National Birth Cohort.

PubMed

Brown, Alan S; Gyllenberg, David; Hinkka-Yli-Salomäki, Susanna; Sourander, Andre; McKeague, Ian W

2017-04-01

Identification of abnormalities in the developmental trajectory during infancy of future schizophrenia cases offers the potential to reveal pathogenic mechanisms of this disorder. Previous studies of head circumference in pre-schizophrenia were limited to measures at birth. The use of growth acceleration of head circumference (defined as the rate of change in head circumference) provides a more informative representation of the maturational landscape of this measure compared to studies based on static head circumference measures. To date, however, no study has examined whether HC growth acceleration differs between pre-schizophrenia cases and controls. In the present study, we employed a nested case control design of a national birth cohort in Finland. Cases with schizophrenia or schizoaffective disorder (N=375) and controls (N=375) drawn from the birth cohort were matched 1:1 on date of birth (within 1month), sex, and residence in Finland at case diagnosis. Longitudinal data were obtained on head circumference from birth through age 1. Data were analyzed using a new nonparametric Bayesian inversion method which allows for a detailed understanding of growth dynamics. Adjusting for growth velocity of height and weight, and gestational age, there was significantly accelerated growth of head circumference in females with schizophrenia from birth to 2months; the findings remained significant following Bonferroni correction (p<0.0125). This is the first study to report abnormal HC growth acceleration, a more sensitive measure of somatic developmental deviation of this measure, in schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

The Diagnostic Utility of Bact/ALERT and Nested PCR in the Diagnosis of Tuberculous Meningitis.

PubMed

Sastry, Apurba Sankar; Bhat K, Sandhya; Kumudavathi

2013-01-01

The early laboratory diagnosis of Tuberculous Meningitis (TBM) is crucial, to start the antitubercular chemotherapy and to prevent its complications. However, the conventional methods are either less sensitive or time consuming. Hence, the diagnostic potentials of BacT/ALERT and Polymerase Chain Reaction (PCR) was evaluated in this study. The study group comprised of 62 cases and 33 controls. The cases were divided according to Ahuja's criteria into the confirmed (two cases), highly probable (19 cases), probable (26 cases) and the possible (15 cases) subgroups. Ziehl Neelsen's (ZN) and Auramine Phenol (AP) staining, Lowenstein Jensen (LJ) medium culture, BacT/ALERT and nested Polymerase Chain Reaction (PCR) which targeted IS6110 were carried out on all the patients. The sensitivity of the LJ culture was 3.22%. BacT/ALERT showed a sensitivity and a specificity of 25.80% and 100% and those of nested PCR were found to be 40.32% and 96.97% respectively. The mean detection time of growth of the LJ culture was 31.28 days, whereas that of BacT/ALERT was 20.68 days. The contamination rate in the LJ culture and BacT/ALERT were 7.2% and 5.8% respectively. Nested PCR was found to be more sensitive, followed by BacT/ALERT as compared to the LJ culture and smear microscopy. As both false negative and false positive results have been reported for nested PCR, so it should not be used alone as a criterion for initiating or terminating the therapy, but it should be supported by clinical, radiological, cytological and other microbiological findings.

Effectiveness of oral polio vaccination against paralytic poliomyelitis: a matched case-control study in Somalia.

PubMed

Mahamud, Abdirahman; Kamadjeu, Raoul; Webeck, Jenna; Mbaeyi, Chukwuma; Baranyikwa, Marie Therese; Birungi, Julianne; Nurbile, Yassin; Ehrhardt, Derek; Shukla, Hemant; Chatterjee, Anirban; Mulugeta, Abraham

2014-11-01

After the last case of type 1 wild poliovirus (WPV1) was reported in 2007, Somalia experienced another outbreak of WPV1 (189 cases) in 2013. We conducted a retrospective, matched case-control study to evaluate the vaccine effectiveness (VE) of oral polio vaccine (OPV). We retrieved information from the Somalia Surveillance Database. A case was defined as any case of acute flaccid paralysis (AFP) with virological confirmation of WPV1. We selected two groups of controls for each case: non-polio AFP cases ("NPAFP controls") matched to WPV1 cases by age, date of onset of paralysis and region; and asymptomatic "neighborhood controls," matched by age. Using conditional logistic regression, we estimated the VE of OPV as (1-odds ratio)×100. We matched 99 WPV cases with 99 NPAFP controls and 134 WPV1 cases with 268 neighborhood controls. Using NPAFP controls, the overall VE was 70% (95% confidence interval [CI], 37-86), 59% (2-83) among 1-3 dose recipients, 77% (95% CI, 46-91) among ≥4 dose recipients. In neighborhood controls, the overall VE was 95% (95% CI, 84-98), 92% (72-98) among 1-3 dose recipients, and 97% (89-99) among ≥4 dose recipients. When the analysis was limited to cases and controls ≤24 months old, the overall VE in NPAFP and neighborhood controls was 95% (95% CI, 65-99) and 97% (95% CI, 76-100), respectively. Among individuals who were fully vaccinated with OPV, vaccination was effective at preventing WPV1 in Somalia. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Evaluation of Hypoxia Inducible Factor-1α and Glucose Transporter-1 Expression in Non Melanoma Skin Cancer: An Immunohistochemical Study

PubMed Central

Seleit, Iman; Bakry, Ola Ahmed; Ragab, Rania Abdel Aziz; Al-Shiemy, shimaa Ahmed

2017-01-01

Introduction Hypoxia Inducible Factor-1 (HIF-1) is a mediator enabling cell adaptation to hypoxia. It plays its role mainly through transcription of many target genes including Glucose Transporter-1 (GLUT-1) gene. Aim The present work aimed at evaluating the pattern and distribution of HIF-1α and GLUT-1 in each case and control. Materials and Methods A case-control and retrospective study was conducted on archival blocks diagnosed from pathology department as, Basal Cell Carcinoma (BCC, 20 cases), cutaneous Squamous Cell Carcinoma (SCC, 20 cases) and 20 normal site-matched skin biopsies from age and gender-matched healthy subjects as a control. Evaluation of both HIF-1α and GLUT1 expression using standard immunohistochemical techniques was performed on cut sections from selected paraffin embedded blocks. Results HIF-1α was expressed in 90%, 35% and 100% of normal skin, BCC and SCC tumour islands respectively. It was up regulated in both BCC and SCC compared with normal skin (p= 0.001, p<0.001 respectively). GLUT-1 was expressed in 100%, 70% and 100% of normal skin, BCC and SCC tumour islands respectively. It was down regulated in Non Melanoma Skin Cancer (NMSC) cases compared with normal skin (p=0.004). HIF-1α and GLUT-1 localization in tumour nests was central, peripheral or central and peripheral. Both HIF-1α and GLUT-1 showed variable expression in stroma, adnexa and inflammatory cells. No significant correlation was found between Histo (H) score or expression percentage values of HIF-1α and those of GLUT-1 in tumour islands or in overlying epidermis either in BCC or SCC. Conclusion HIF-1α may have a role in NMSC pathogenesis through adaptation to hypoxia which results from excessive proliferation. GLUT-1 down regulation in NMSC may be explained by its consumption by proliferating tumour cells. The expression of HIF-1α and GLUT-1 in normal epidermis, stromal and adnexal structures needs further research. PMID:28764171

Risk of adverse cardiovascular outcomes and all-cause mortality associated with concomitant use of clopidogrel and proton pump inhibitors in elderly patients.

PubMed

Mahabaleshwarkar, Rohan K; Yang, Yi; Datar, Manasi V; Bentley, John P; Strum, Matthew W; Banahan, Benjamin F; Null, Kyle D

2013-04-01

To examine the effect of concomitant use of clopidogrel and PPIs in a national sample of elderly Medicare beneficiaries (age ≥65 years). A nested case-control design was employed. A cohort of Medicare beneficiaries who initiated clopidogrel and did not have any gap of ≥30 days between clopidogrel fills between July 1, 2006 and December 31, 2008 was identified from a 5% national sample of Medicare claims data. Within this cohort, cases (beneficiaries who experienced any major cardiovascular event [MCE] [acute myocardial infarction, stroke, coronary artery bypass graft, or percutaneous coronary intervention] or all-cause mortality) and controls (beneficiaries who did not experience any MCE or all-cause mortality) were identified from inpatient and outpatient claims. Cases and controls were matched on age and the time to first clopidogrel fill. Conditional logistic regression was performed on the matched sample to evaluate the association between concomitant use of clopidogrel and PPIs and adverse health outcomes (MCEs and all-cause mortality). A total of 43,159 clopidogrel users were identified. Among them, 15,415 (35.7%) received clopidogrel and a PPI concomitantly at any time during the study period, 3502 (8.1%) experienced a MCE, 7306 (17.1%) died, and a total of 9908 (22.8%) experienced the primary composite outcome (any MCE or all-cause mortality) during follow-up. The odds ratio (OR) for the primary composite outcome was 1.26 (95% confidence interval [CI]: 1.18-1.35). Secondary analyses indicated that elderly patients using clopidogrel and a PPI concomitantly were more likely to experience all-cause mortality (OR: 1.40; 95% CI: 1.29-1.53) as compared to those receiving clopidogrel only, but not MCEs (OR: 1.06; 95% CI: 0.95-1.18). Concomitant use of clopidogrel and PPIs was associated with a slightly increased risk of all-cause mortality but not MCEs.

In-Hospital Disease Burden of Sarcoidosis in Switzerland from 2002 to 2012.

PubMed

Pohle, Susanne; Baty, Florent; Brutsche, Martin

2016-01-01

Sarcoidosis is a multisystem disease with an unpredictable and sometimes fatal course while the underlying pathomechanism is still unclear. Reasons of the increasing hospitalization rate and mortality in the United States remain in dispute but incriminated are a number of distinct comorbidities and risk factors as well as the application of more aggressive therapeutic agents. Studies reflecting the recent development in central Europe are lacking. Our aim was to investigate the recent mortality and hospitalization rates as well as the underlying comorbidities of hospitalized sarcoidosis patients in Switzerland. In this longitudinal, nested case-control study, a nation-wide database provided by the Swiss Federal Office for Statistics enclosing every hospital entry covering the years 2002-2012 (n = 15,627,573) was analyzed. There were 8,385 cases with a diagnosis of sarcoidosis representing 0.054% (8,385 / 15,627,573) of all hospitalizations in Switzerland. These cases were compared with age- and sex-matched controls without the diagnosis of sarcoidosis. Hospitalization and mortality rates in Switzerland remained stable over the observed time period. Comorbidity analysis revealed that sarcoidosis patients had significantly higher medication-related comorbidities compared to matched controls, probably due to systemic corticosteroids and immunosuppressive therapy. Sarcoidosis patients were also more frequently re-hospitalized (median annual hospitalization rate 0.28 [IQR 0.15-0.65] vs. 0.19 [IQR 0.13-0.36] per year; p < 0.001), had a longer hospital stay (6 [IQR 2-13] vs. 4 [IQR 1-8] days; p < 0.001), had more comorbidities (4 [IQR 2-7] vs. 2 [IQR 1-5]; p < 0.001), and had a significantly higher in-hospital mortality (2.6% [95% CI 2.3%-2.9%] vs. 1.8% [95% CI 1.5%-2.1%] (p < 0.001). A worse outcome was observed among sarcoidosis patients having co-occurrence of associated respiratory diseases. Moreover, age was an important risk factor for re-hospitalization.

Review of primary hypothyroidism in very low birthweight infants in a perinatal centre in Hong Kong.

PubMed

Chee, Yuet Yee; Wong, Kar Yin; Low, Louis

2011-11-01

To review the incidence and risk factors of primary hypothyroidism in very low birthweight (VLBW) infants in our centre and to assess their neurodevelopmental outcome. Retrospective, descriptive review of VLBW infants with primary hypothyroidism from 1 January 2000 to 31 December 2008 in a perinatal centre. Case control comparisons for neurodevelopmental outcome at 18 months, nested to a prospective VLBW cohort (Vermont Oxford Database). Twelve cases were identified, with the incidence of primary hypothyroidism of 1 in 55 live births in our VLBW cohort during the 9-year study period. Umbilical cord blood thyroid-stimulating hormone was abnormal in less than half of the cases using the current cut-off (≤14 mIU/L). Five cases were transient in nature, four cases were permanent and the causes for the rest remained undetermined at the time of review. Elevation of thyroid-stimulating hormone was first evident at a mean of 2.4 weeks post-natally. Follow-up assessment reviewed normal development in 83% of cases (10 out of 12 cases). There was no statistically significant difference in Griffith's scores at 18 months between the case and matched controls. The high incidence of primary hypothyroidism in our VLBW cohort deserved stringent monitoring of thyroid function post-natally. Umbilical cord blood screening was not useful as a screening tool because of its low sensitivity. Neurodevelopmental outcome for treated primary hypothyroidism was favourable as assessed at 18 months of age. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Applying Matched Sampling to Evaluate a University Tutoring Program for First-Year Students

ERIC Educational Resources Information Center

Walvoord, Mark E.; Pleitz, Jacob D.

2016-01-01

Our study used a case-control matching design to assess the influence of a voluntary tutoring program in improving first-year students' Grade Point Averages (GPA). To evaluate program effectiveness, we applied case-control matching to obtain 215 pairs of students with or without participation in tutoring, but matched on high school GPA and…

Risk of atrial fibrillation among bisphosphonate users: a multicenter, population-based, Italian study.

PubMed

Herrera, L; Leal, I; Lapi, F; Schuemie, M; Arcoraci, V; Cipriani, F; Sessa, E; Vaccheri, A; Piccinni, C; Staniscia, T; Vestri, A; Di Bari, M; Corrao, G; Zambon, A; Gregori, D; Carle, F; Sturkenboom, M; Mazzaglia, G; Trifiro, G

2015-05-01

Bisphosphonate treatment is used to prevent bone fractures. A controversial association of bisphosphonate use and risk of atrial fibrillation has been reported. In our study, current alendronate users were associated with a higher risk of atrial fibrillation as compared with those who had stopped bisphosphonate (BP) therapy for more than 1 year. Bisphosphonates are widely used to prevent bone fractures. Controversial findings regarding the association between bisphosphonate use and the risk of atrial fibrillation (AF) have been reported. The aim of this study was to evaluate the risk of AF in association with BP exposure. We performed a nested case-control study using the databases of drug-dispensing and hospital discharge diagnoses from five Italian regions. The data cover a period ranging from July 1, 2003 to December 31, 2006. The study population comprised new users of bisphosphonates aged 55 years and older. Patients were followed from the first BP prescription until an occurrence of an AF diagnosis (index date, i.e., ID), cancer, death, or the end of the study period, whichever came first. For the risk estimation, any AF case was matched by age and sex to up to 10 controls from the same source population. A conditional logistic regression was performed to obtain the odds ratio with 95% confidence intervals (CI). The BP exposure was classified into current (<90 days prior to ID), recent (91-180), past (181-364), and distant past (≥365) use, with the latter category being used as a reference point. A subgroup analysis by individual BP was then carried out. In comparison with distant past users of BP, current users of BP showed an almost twofold increased risk of AF: odds ratio (OR) = 1.78 and 95% CI = 1.46-2.16. Specifically, alendronate users were mostly associated with AF as compared with distant past use of BP (OR, 1.97; 95% CI, 1.59-2.43). In our nested case-control study, current users of BP are associated with a higher risk of atrial fibrillation as compared with those who had stopped BP treatment for more than 1 year.

Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case-Control Study in EPIC.

PubMed

Assi, Nada; Thomas, Duncan C; Leitzmann, Michael; Stepien, Magdalena; Chajès, Véronique; Philip, Thierry; Vineis, Paolo; Bamia, Christina; Boutron-Ruault, Marie-Christine; Sandanger, Torkjel M; Molinuevo, Amaia; Boshuizen, Hendriek C; Sundkvist, Anneli; Kühn, Tilman; Travis, Ruth C; Overvad, Kim; Riboli, Elio; Gunter, Marc J; Scalbert, Augustin; Jenab, Mazda; Ferrari, Pietro; Viallon, Vivian

2018-05-01

Background: The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites. Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk. Results: Exposure-related metabolic signatures were identified. Particularly, the body mass index (BMI)-associated metabolic component was positively related to glutamic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1.23 (95% confidence interval = 0.93-1.62) and 1.40 (1.14-1.72), respectively, for BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC with natural indirect effects, respectively, equal to 1.56 (1.24-1.96) and 1.09 (1.03-1.15), accounting for a proportion mediated of 100% and 24%. Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk. Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators. Cancer Epidemiol Biomarkers Prev; 27(5); 531-40. ©2018 AACR . ©2018 American Association for Cancer Research.

Risk factors for psychosis: impaired social and role functioning.

PubMed

Cornblatt, Barbara A; Carrión, Ricardo E; Addington, Jean; Seidman, Larry; Walker, Elaine F; Cannon, Tyronne D; Cadenhead, Kristin S; McGlashan, Thomas H; Perkins, Diana O; Tsuang, Ming T; Woods, Scott W; Heinssen, Robert; Lencz, Todd

2012-11-01

Risk for psychosis is currently defined primarily on the basis of attenuated positive symptoms (APS), with no inclusion of the functional deficits characteristic of schizophrenia. Impaired social and role functioning have been of interest for reflecting poor outcome but far less is known about the developmental impact of these deficits as vulnerability or risk factors. Age-appropriate social and role functioning were prospectively assessed in 100 individuals at clinical high risk (CHR) for psychosis included in the 8-site North American Prodromal Longitudinal Study database. A nested case-control design was used to compare changes in social and role functioning in 26 individuals converting to psychosis shortly after baseline assessment and 24 converting over a year later. Individuals in each converter subgroup were directly matched to a non-converter at the same site, controlling for time to conversion, age, gender, and severity of baseline symptoms. At baseline, CHR subjects who later became psychotic were significantly more likely to be impaired socially than matched non-converters. Onset of psychosis did not further disrupt social difficulties. Role functioning showed some of the same trends, but the overall pattern was not as consistent as for the social domain. Controlling for neurocognition did not change the pattern of group differences. Early impaired social functioning appears to be a risk factor for psychosis and, added to APS, could potentially contribute to accurate identification of CHR individuals and provide a new direction for early intervention to reduce long-term disability.

Plasma carotenoids and the risk of premalignant breast disease in women aged 50 and younger: a nested case-control study.

PubMed

Cohen, Kevin; Liu, Ying; Luo, Jingqin; Appleton, Catherine M; Colditz, Graham A

2017-04-01

To examine the association of plasma carotenoids, micronutrients in fruits, and vegetables, with risk of premalignant breast disease (PBD) in younger women. Blood samples were collected at the Siteman Cancer Center between 2008 and 2012 from 3537 women aged 50 or younger with no history of cancer or PBD. The analysis included 147 participants diagnosed with benign breast disease or breast carcinoma in situ during a 27-month follow-up and 293 controls. Cases and controls were matched on age, race/ethnicity, and date of and fasting status at blood draw. Plasma carotenoids were quantified. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and linear regression to assess racial differences in plasma carotenoids. The risk reduction between the highest and lowest tertiles varied by carotenoid, with β-cryptoxanthin having the greatest reduction (OR 0.62; 95% CI, 0.62-1.09; P trend  = 0.056) and total carotenoids the least (OR 0.83; 95% CI, 0.48-1.44; P trend  = 0.12). We observed an inverse association between plasma carotenoids and risk of PBD in obese women (BMI ≥ 30 kg/m 2 ; 61 cases and 115 controls) but not lean women (BMI < 25 kg/m 2 ; 54 cases and 79 controls), although the interaction was not statistically significant. Compared to white women, black women had lower levels of α and β-carotene and higher levels of β-cryptoxanthin and lutein/zeaxanthin. We observed suggestive inverse associations between plasma carotenoids and risk of PBD in younger women, consistent with inverse associations reported for invasive breast cancer. Carotenoids may play a role early in breast cancer development.

Plasma Carotenoids and the Risk of Premalignant Breast Disease in Women Aged 50 and Younger: A Nested Case-Control Study

PubMed Central

Cohen, Kevin; Liu, Ying; Luo, Jingqin; Appleton, Catherine M.; Colditz, Graham A.

2017-01-01

Purpose To examine the association of plasma carotenoids, micronutrients in fruits and vegetables, with risk of premalignant breast disease (PBD) in younger women. Methods Blood samples were collected at the Siteman Cancer Center between 2008 and 2012 from 3,537 women aged 50 or younger with no history of cancer or PBD. The analysis included 147 participants diagnosed with benign breast disease or breast carcinoma in situ during a 27-month followup and 293 controls. Cases and controls were matched on age, race/ethnicity, and date of and fasting status at blood draw. Plasma carotenoids were quantified. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and linear regression to assess racial differences in plasma carotenoids. Results The risk reduction between the highest and lowest tertiles varied by carotenoid, with β-cryptoxanthin having the greatest reduction (OR 0.62; 95% CI, 0.62–1.09; Ptrend=0.056) and total carotenoids the least (OR 0.83; 95% CI, 0.48–1.44; Ptrend=0.12). We observed an inverse association between plasma carotenoids and risk of PBD in obese women (BMI≥30 kg/m2; 61 cases and 115 controls) but not lean women (BMI<25 kg/m2; 54 cases and 79 controls), although the interaction was not statistically significant. Compared to white women, black women had lower levels of α and β-carotene and higher levels of β-cryptoxanthin and lutein/zeaxanthin. Conclusions We observed suggestive inverse associations between plasma carotenoids and risk of PBD in younger women , consistent with inverse associations reported for invasive breast cancer. Carotenoids may play a role early in breast cancer development. PMID:28190250

Association between Prediagnostic Allergy-Related Serum Cytokines and Glioma.

PubMed

Schwartzbaum, Judith; Seweryn, Michal; Holloman, Christopher; Harris, Randall; Handelman, Samuel K; Rempala, Grzegorz A; Huang, Ruo-Pan; Burkholder, Brett; Brandemihl, Adam; Kallberg, Henrik; Johannesen, Tom Borge; Ahlbom, Anders; Feychting, Maria; Grimsrud, Tom K

2015-01-01

Allergy is inversely related to glioma risk. To determine whether prediagnostic allergy-related serum proteins are associated with glioma, we conducted a nested case-control study of seven cytokines (IL4, IL13, IL5, IL6, IL10, IFNG, TGFB2), two soluble cytokine receptors (sIL4RA, sIL13RA2) and three allergy-related transcription factors (FOXP3, STAT3, STAT6) using serum specimens from the Janus Serum Bank Cohort in Oslo, Norway. Blood donors subsequently diagnosed with glioma (n = 487) were matched to controls (n = 487) on age and date of blood draw and sex. We first estimated individual effects of the 12 serum proteins and then interactions between IL4 and IL13 and their receptors using conditional logistic regression. We next tested equality of case-control inter-correlations among the 12 serum proteins. We found that TGFB2 is inversely related to glioblastoma (Odds Ratio (OR) = 0.87, 95% Confidence Interval (CI)) = 0.76, 0.98). In addition, ≤ 5 years before diagnosis, we observed associations between IL4 (OR = 0.82, 95% CI = 0.66, 1.01), sIL4RA (OR = 0.80, 95% CI = 0.65, 1.00), their interaction (OR = 1.06, 95% CI = 1.01, 1.12) and glioblastoma. This interaction was apparent > 20 years before diagnosis (IL4-sIL4RA OR = 1.20, 95% CI = 1.05, 1.37). Findings for glioma were similar. Case correlations were different from control correlations stratified on time before diagnosis. Five years or less before diagnosis, correlations among case serum proteins were weaker than were those among controls. Our findings suggest that IL4 and sIL4RA reduce glioma risk long before diagnosis and early gliomagenesis affects circulating immune function proteins.

3D deformable image matching: a hierarchical approach over nested subspaces

NASA Astrophysics Data System (ADS)

Musse, Olivier; Heitz, Fabrice; Armspach, Jean-Paul

2000-06-01

This paper presents a fast hierarchical method to perform dense deformable inter-subject matching of 3D MR Images of the brain. To recover the complex morphological variations in neuroanatomy, a hierarchy of 3D deformations fields is estimated, by minimizing a global energy function over a sequence of nested subspaces. The nested subspaces, generated from a single scaling function, consist of deformation fields constrained at different scales. The highly non linear energy function, describing the interactions between the target and the source images, is minimized using a coarse-to-fine continuation strategy over this hierarchy. The resulting deformable matching method shows low sensitivity to local minima and is able to track large non-linear deformations, with moderate computational load. The performances of the approach are assessed both on simulated 3D transformations and on a real data base of 3D brain MR Images from different individuals. The method has shown efficient in putting into correspondence the principle anatomical structures of the brain. An application to atlas-based MRI segmentation, by transporting a labeled segmentation map on patient data, is also presented.

Drought-caused delay in nesting of Sonoran Desert birds and its facilitation of parasite- and predator-mediated variation in reproductive success

USGS Publications Warehouse

McCreedy, Chris; van Riper, Charles

2015-01-01

As our understanding of climate change has increased, so has our awareness of the impacts of these changes on biotic systems. Climate models are nearly unanimous in their predictions for increased drought frequency in southwestern North America, and delays in nest initiation due to drought may influence nesting success and productivity for many Sonoran Desert bird species. In southeastern California and western Arizona in 2004–2009, we found negative correlations for 13 of 13 species between nest initiation date and rainfall accumulation during the preceding 4-month winter rainy season. Nesting was delayed more than 3 weeks for some species during extreme droughts in 2006 and 2007. During 2004–2009, we found a significant negative effect of nest initiation date on nest survival probability (β̂ = −0.031 ± 0.005 SE, P < 0.001) for the four species of greatest sample size. To investigate the role of nesting delay in nesting success and productivity, in 2010 we conducted a manipulative experiment with Black-tailed Gnatcatchers (Polioptila melanura; BTGN) and Verdins (Auriparus flaviceps; VERD). Following a wet winter, we delayed clutch initiation dates for treatment pairs to match first-egg dates that we observed during droughts in 2006 and 2007. Nest initiation date had a significant negative effect on nest survival of both species (BTGN: β̂ = −1.18 ± 0.27 SE, P < 0.001; VERD: β̂ = −2.33 ± 0.51 SE, P = 0.003). Treatment pairs were unable to overcome the lost period of high productivity in March and early April, and had lower productivity than control pairs over the entire breeding season. As nest predation and Brown-headed Cowbird (Molothrus ater) parasitism were the most common causes of nest failure, we conclude that the impacts of climate change–caused drought on annual reproductive output in the Sonoran Desert will be further compounded by parasitism and predation for Black-tailed Gnatcatchers and by predation for Verdins.

The impact of overactive bladder, incontinence and other lower urinary tract symptoms on quality of life, work productivity, sexuality and emotional well-being in men and women: results from the EPIC study.

PubMed

Coyne, Karin S; Sexton, Chris C; Irwin, Debra E; Kopp, Zoe S; Kelleher, Con J; Milsom, Ian

2008-06-01

To examine the effect overactive bladder (OAB) and other lower urinary tract symptoms (LUTS) on health-related quality of life (HRQoL) in a population sample, as OAB often occurs in conjunction with many other LUTS. A nested case-control analysis was performed on men and women with (cases) and without (controls) OAB, from the EPIC study. OAB was assessed using 2002 International Continence Society definitions. Based on their responses to questions about LUTS, cases were classified into five groups; continent OAB, OAB with incontinence, OAB + postmicturition, OAB + voiding, and OAB + postmicturition + voiding. Both cases and controls were asked questions about symptom bother (OAB-q), generic QoL (EQ-5D), work productivity (Work Productivity and Activity Impairment, WPAI), depressive symptoms (Center for Epidemiologic Studies Depression Scale), sexual satisfaction, and erectile dysfunction (men only) using the Massachusetts Male Aging Study. Cases answered additional condition-specific questions HRQoL (OAB-q short form), Patient Perception of Bladder Condition and work productivity related to a specific health problem (WPAI-SHP). General linear models were used to evaluate group differences. Of the EPIC participants, 1434 identified OAB cases were matched by age, gender and country, with 1434 participants designated as controls. Cases and controls were primarily Caucasian (96.2% and 96.7%, respectively), and most (65%) were female; the mean age was 53.8 and 53.7 years, respectively. Comorbid conditions differed significantly by case/control status, with cases reporting significantly greater rates of chronic constipation, asthma, diabetes, high blood pressure, bladder or prostate cancer, neurological conditions and depression. There were significant differences between the cases and controls in all reported LUTS. The OAB + postmicturition + voiding group reported significantly greater symptom bother, worse HRQoL, higher rates of depression and decreased enjoyment of sexual activity, than the other subgroups. OAB has a substantial, multidimensional impact on patients; OAB with additional LUTS has a greater impact. The diagnosis and treatment of OAB should be considered in conjunction with other LUTS, to maximize treatment options and optimize patient outcomes.

Environmental risks for nontuberculous mycobacteria. Individual exposures and climatic factors in the cystic fibrosis population.

PubMed

Prevots, D Rebecca; Adjemian, Jennifer; Fernandez, Aisling G; Knowles, Michael R; Olivier, Kenneth N

2014-09-01

Persons with cystic fibrosis are at high risk of pulmonary nontuberculous mycobacterial infection, with a national prevalence estimated at 13%. The risk of nontuberculous mycobacteria associated with specific environmental exposures, and the correlation with climatic conditions in this population has not been described. To describe the association of pulmonary nontuberculous mycobacteria with individual exposures to water and soil aerosols, and the population associations of these infections with climatic factors. We conducted a nested case-control study within a cohort study of pulmonary nontuberculous mycobacteria prevalence at 21 geographically diverse national cystic fibrosis centers. Incident nontuberculous mycobacterial infection cases (at least one prior negative culture followed by one positive culture) were age- and sex-matched to culture-negative controls. Exposures to water and soil were assessed by administering a standardized questionnaire. Cohort prevalence at each of the 21 centers was correlated with climatic conditions in the same area through linear regression modeling. Overall, 48 cases and 85 control subjects were enrolled. Indoor swimming was associated with incident infection (adjusted odds ratio, 5.9, 95% confidence interval, 1.3-26.1), although only nine cases (19%) and five control subjects (6%) reported indoor swimming in the 4 months prior to infection. Exposure to showering and municipal water supply was common among both cases and control subjects: 77% of cases and 76% of control subjects reported showering at least daily. In linear regression, average annual atmospheric water vapor content was significantly predictive of center prevalence (P = 0.0019), with R(2) = 0.40. Atmospheric conditions explain more of the variation in disease prevalence than individual behaviors. The risk of specific exposures may vary by geographic region due to differences in conditions favoring mycobacterial growth and survival. However, because exposure to these organisms is ubiquitous and behaviors are similar among persons with and without pulmonary nontuberculous mycobacteria, genetic susceptibility beyond cystic fibrosis is likely to be important for disease development. Common individual risk factors in high-risk populations remain to be identified.

Impact of a History of Hypertension in Pregnancy on Later Diagnosis of Atrial Fibrillation.

PubMed

Scantlebury, Dawn C; Kattah, Andrea G; Weissgerber, Tracey L; Agarwal, Sanket; Mielke, Michelle M; Weaver, Amy L; Vaughan, Lisa E; Henkin, Stanislav; Zimmerman, Katherine; Miller, Virginia M; White, Wendy M; Hayes, Sharonne N; Garovic, Vesna D

2018-05-13

Atrial fibrillation/flutter (AF) produces significant morbidity in women and is typically attributed to cardiac remodeling from multiple causes, particularly hypertension. Hypertensive pregnancy disorders (HPDs) are associated with future hypertension and adverse cardiac remodeling. We evaluated whether women with AF were more likely to have experienced a HPD compared with those without. A nested case-control study was conducted within a cohort of 7566 women who had a live or stillbirth delivery in Olmsted County, Minnesota between 1976 and 1982. AF cases were matched (1:1) to controls based on date of birth, age at first pregnancy, and parity. AF and pregnancy history were confirmed by chart review. We identified 105 AF cases: mean age 57±8 (mean±SD) years, (controls 56±8 years), 32±8 years (controls 31±8 years) after the first pregnancy. Cases were more likely to have obesity during childbearing years, and hypertension, diabetes mellitus, dyslipidemia, coronary disease, valvular disease, and heart failure at the time of AF diagnosis. Cases were more likely to have a history of HPDs, compared with controls: 28/105 (26.7%) cases versus 12/105 (11.4%) controls, odds ratio: 2.60 (95% confidence interval, 1.21-6.04). After adjustment for hypertension and obesity, the association was attenuated and no longer statistically significant; odds ratio (95% confidence interval, 2.12 (0.92-5.23). Women with AF are more likely to have had a HPD, a relationship at least partially mediated by associated obesity and hypertension. Given the high morbidity of AF, studies evaluating the benefit of screening for and management of cardiovascular risk factors in women with a history of HPD should be performed. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Incidence and risk factors of urinary tract infection in very low birth weight infants.

PubMed

Ruangkit, C; Satpute, Ankita; Vogt, B A; Hoyen, C; Viswanathan, S

2016-01-01

To describe the incidence and associated risk factors of urinary tract infection (UTI) in very low birth weight (VLBW) infants and to determine the value of diagnostic imaging studies after the first UTI episode before discharge from the neonatal intensive care unit (NICU). VLBW infants born during 2003-2012 were reviewed for UTI. In a nested case-control study, potential risk factors of UTI were compared between infants with UTI (cases) versus birth weight and gestational age matched controls. Renal ultrasonography (USG) and voiding cystourethrography (VCUG) results were reviewed in cases. During the study period, 54.7% of urine culture specimens were collected by sterile methods. 3% (45/1,495) of VLBW infants met the study definition for UTI. UTI was diagnosed at mean postnatal age of 33.1±22.9 days. There was no significant difference in gender, ethnicity, antenatal steroid exposure, blood culture positive sepsis, ionotropic support, respiratory support and enteral feeding practices between cases and controls. Cases had a significantly higher cholestasis compared to controls (22% vs. 9% ; p = 0.03). However, cholestasis was not a significant predictor of UTI in the adjusted analysis [adjusted OR 2.38 (95% CI 0.84 to 6.80), p = 0.11]. Cases had higher central line days, parenteral nutrition days, total mechanical ventilation days, chronic lung disease, and length of stay compared to controls. Renal USG was abnormal in 37% and VCUG was abnormal in 17% of cases. The incidence of UTI in contemporary VLBW infants is relatively low compared to previous decades. Since no significant UTI predictors could be identified, urine culture by sterile methods is the only reliable way to exclude UTI. The majority of infants with UTI have normal renal anatomy. UTI in VLBW infants is associated with increased morbidity and length of stay.

No association of alcohol use and the risk of ulcerative colitis or Crohn's disease: data from a European Prospective cohort study (EPIC).

PubMed

Bergmann, M M; Hernandez, V; Bernigau, W; Boeing, H; Chan, S S M; Luben, R; Khaw, K-T; van Schaik, F; Oldenburg, B; Bueno-de-Mesquita, B; Overvad, K; Palli, D; Masala, G; Carbonnel, F; Boutron-Ruault, M-C; Olsen, A; Tjonneland, A; Kaaks, R; Katzke, V; Riboli, E; Hart, A R

2017-04-01

The role of long-term alcohol consumption for the risk of developing ulcerative colitis (UC) and Crohn's disease (CD) is unclear. For the first time, to prospectively assess the role of pre-disease alcohol consumption on the risk of developing UC or CD. Nested within the European Prospective Investigation into Cancer and Nutrition (EPIC-IBD), incident UC and CD cases and matched controls where included. At recruitment, participants completed validated food frequency and lifestyle questionnaires. Alcohol consumption was classified as either: non-use, former, light (⩽0.5 and 1 drink per week), below the recommended limits (BRL) (⩽1 and 2 drinks per day), moderate (⩽2.5 and 5 drinks per day), or heavy use (>2.5 and >5 drinks per day) for women and men, respectively; and was expressed as consumption at enrolment and during lifetime. Conditional logistic regression was applied adjusting for smoking and education, taking light users as the reference. Out of 262 451 participants in six countries, 198 UC incident cases/792 controls and 84 CD cases/336 controls were included. At enrolment, 8%/27%/32%/23%/11% UC cases and 7%/29%/40%/19%/5% CD cases were: non-users, light, BRL, moderate and heavy users, respectively. The corresponding figures for lifetime non-use, former, light, BRL, moderate and heavy use were: 3%/5%/23%/44%/19%/6% and 5%/2%/25%/44%/23%/1% for UC and CD cases, respectively. There were no associations between any categories of alcohol consumption and risk of UC or CD in the unadjusted and adjusted odds ratios. There was no evidence of associations between alcohol use and the odds of developing either UC or CD.

Patterns of Ultraviolet Radiation Exposure and Skin Cancer Risk: the E3N-SunExp Study.

PubMed

Savoye, Isabelle; Olsen, Catherine M; Whiteman, David C; Bijon, Anne; Wald, Lucien; Dartois, Laureen; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Kvaskoff, Marina

2018-01-05

While ultraviolet (UV) radiation exposure is a recognized risk factor for skin cancer, associations are complex and few studies have allowed a direct comparison of exposure profiles associated with cutaneous melanoma, basal-cell carcinoma (BCC), and squamous-cell carcinoma (SCC) within a single population. We examined associations between UV exposures and skin cancer risk in a nested case-control study within E3N, a prospective cohort of 98,995 French women born in 1925-1950. In 2008, a lifetime UV exposure questionnaire was sent to all reported skin cancer cases and three controls per case, which were matched on age, county of birth, and education. Analyses were performed using conditional logistic regression and included 366 melanoma cases, 1,027 BCC cases, 165 SCC cases, and 3,647 controls. A history of severe sunburns <25 years was associated with increased risks of all skin cancers (melanoma: OR 2.7; BCC: OR 1.7; SCC: OR 2.0 for ≥6 sunburns vs. none), while sunburns ≥25 years were associated with BCC and SCC only. While high-sun protection factor sunscreen use before age 25 was associated with lower BCC risk (P trend = 0.02), use since age 25 and reapplication of sunscreen were associated with higher risks of all three types of skin cancer. There were positive linear associations between total UV score and risks of BCC (P trend = 0.01) and SCC (P trend = 0.09), but not melanoma. While recreational UV score was strongly associated with BCC, total and residential UV scores were more strongly associated with SCC. Melanoma, BCC, and SCC are associated with different sun exposure profiles in women.

Avascular necrosis of bone following allogeneic hematopoietic cell transplantation in children and adolescents

PubMed Central

Li, Xiaxin; Brazauskas, Ruta; Wang, Zhiwei; Al-Seraihy, Amal; Baker, K. Scott; Cahn, Jean-Yves; Frangoul, Haydar A.; Gajewski, James L.; Hale, Gregory A.; Hsu, Jack W.; Kamble, Rammurti T.; Lazarus, Hillard M.; Marks, David I.; Maziarz, Richard T.; Savani, Bipin N.; Shah, Ami J.; Shah, Nirali; Sorror, Mohamed L.; Wood, William A.; Majhail, Navneet S.

2014-01-01

We conducted a nested case-control study within a cohort of 6,244 patients to assess risk factors for avascular necrosis (AVN) of bone in children and adolescents following allogeneic transplantation. Eligible patients were ≤21 years of age, received their first allogeneic transplant between 1990 and 2008 in the United States and had survived ≥ 6 months from transplantation. Overall, 160 cases with AVN and 478 controls matched by year of transplant, length of followup and transplant center were identified. Cases and controls were confirmed via central review of radiology, pathology and/or surgical procedure reports. Median time from transplant to diagnosis of AVN was 14 months. On conditional logistic regression, increasing age at transplant (≥5 years), female gender and chronic graft-versus-host disease (GVHD) were significantly associated with increased risks of AVN. Compared to patients receiving myeloablative regimens for malignant diseases, lower risks of AVN were seen in patients with non-malignant diseases and those who had received reduced intensity conditioning regimens for malignant diseases. Children at high risk for AVN include those within the age group where rapid bone growth occurs as well as those who experience exposure to myeloablative conditioning regimens and immunosuppression post-HCT for the treatment of GVHD. More research is needed to determine whether screening strategies specifically for patients at high risk for developing AVN with early interventions may mitigate the morbidity associated with this complication. PMID:24388803

Anti-diabetic medications and risk of primary liver cancer in persons with type II diabetes.

PubMed

Hagberg, K W; McGlynn, K A; Sahasrabuddhe, V V; Jick, S

2014-10-28

Type II diabetes increases liver cancer risk but the risk may be mitigated by anti-diabetic medications. However, choice of medications is correlated with diabetes duration and severity, leading to confounding by indication. To address this association, we conducted a nested case-control study among persons with type II diabetes in the Clinical Practice Research Datalink. Cases had primary liver cancer and controls were matched on age, sex, practice, calendar time, and number of years in the database. Exposure was classified by type and combination of anti-diabetic prescribed and compared to non-use. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. In 305 cases of liver cancer and 1151 controls, there was no association between liver cancer and anti-diabetic medication use compared to non-use (OR=0.74 (95% CI=0.45-1.20) for metformin-only, 1.10 (95% CI=0.66-1.84) for other oral hypoglycaemic (OH)-only, 0.89 (95% CI=0.58-1.37) for metformin+other OH, 1.11 (95% CI=0.60-2.05) for metformin+insulin, 0.81 (95% CI=0.23-2.85) for other OH+insulin, and 0.72 (95% CI=0.18-2.84) for insulin-only). Stratification by duration of diabetes did not alter the results. Use of any anti-diabetic medications in patients with type II diabetes was not associated with liver cancer, though there was a suggestion of a small protective effect for metformin.

Serum 25-Hydroxyvitamin D and Breast Cancer in the Military: A Case-control Study Utilizing Pre-diagnostic Serum

DTIC Science & Technology

2013-01-08

15. Shin MH, Holmes MD, Hankinson SE, Wu K, Colditz GA, Willett WC (2002) Intake of dairy products, calcium, and vitamin D and risk of breast cancer...Serum 25-hydroxyvitamin D concentrations and postmenopausal breast cancer risk: a nested case control study in the Cancer Prevention Study-II Nutrition

Circulating 25-Hydroxyvitamin D and Risk of Pancreatic Cancer

PubMed Central

Stolzenberg-Solomon, Rachael Z.; Jacobs, Eric J.; Arslan, Alan A.; Qi, Dai; Patel, Alpa V.; Helzlsouer, Kathy J.; Weinstein, Stephanie J.; McCullough, Marjorie L.; Purdue, Mark P.; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R.; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Albanes, Demetrius; Cai, Qiuyin; Harvey, Chinonye; Hayes, Richard; Clipp, Sandra; Horst, Ronald L.; Irish, Lonn; Koenig, Karen; Le Marchand, Loic; Kolonel, Laurence N.

2010-01-01

Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974–2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50–<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (≥100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered. PMID:20562185

Parity and risk of stomach cancer by sub-site: a national Swedish study.

PubMed

Bahmanyar, S; Lambe, M; Zendehdel, K; Nyrén, O; Boffetta, P; Ye, W

2008-04-08

We investigated stomach cancer risk by anatomic sub-site in relation to parity, as a marker for higher exposure to sex hormones, in a case-control study, nested within a cohort of 2,406,439 Swedish women born in 1925 or later and followed from 1970 or age 30 until emigration, death, any cancer diagnosis, or through 2004, whichever occurred first. We identified 286 cardia and 2498 non-cardia stomach cancer cases with five matched controls for each case. Cross-linkage with the Multi-Generation Register provided information about reproductive history. Using conditional logistic regression models for estimating odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for education level and occupation, we found no association between any aspect of parity and non-cardia stomach cancer (OR=1.01, 95% CI 0.89-1.15, comparing parous with nulliparous women). However, a 30% risk reduction for postmenopausal cardia cancer (OR=0.7, 95% CI 0.4-1.0) was noted among parous relative to nulliparous women and the risk for premenopausal cardia cancer fell with increasing number of children (P for trend=0.04). Our results indicate that exposure to female sex hormones does not protect against non-cardia stomach cancer and does not explain male predominance. The observed moderate inverse relationship between parity and cardia cancer may be mediated by non-hormonal factors and warrants further study.

Anti-p53 antibodies in sera from patients with chronic obstructive pulmonary disease can predate a diagnosis of cancer.

PubMed

Trivers, G E; De Benedetti, V M; Cawley, H L; Caron, G; Harrington, A M; Bennett, W P; Jett, J R; Colby, T V; Tazelaar, H; Pairolero, P; Miller, R D; Harris, C C

1996-10-01

Serum anti-p53 antibodies (p53-Abs) may be surrogate markers for both p53 alterations and preclinical cancer. Ancillary to a prospective trial to abate progressive development of clinical stages of chronic obstructive pulmonary disease, we conducted a retrospective, nested case-control study. Twenty-three cases were diagnosed with cancer during the trial. Enzyme immunoassay, immunoblotting, and immunoprecipitation were used to detect p53-Abs in serum, immunohistochemistry (IHC) to detect p53 accumulation, and single-strand conformation polymorphism and DNA sequencing to detect p53 mutations in tumor samples. p53-Abs were detected by three types of assays in five (23%) of the cancer patients, 80% of whom had detectable p53-Abs before diagnosis: 2 lung cancers (7 and 6 months before), 1 prostate cancer (11 months), and 1 breast cancer (5 months). Four Ab-positive patients had IHC-positive tumors. Two of 4 Ab-positive patients and 2 of 14 Ab-negative had p53 missense mutations or base pair deletion and IHC-positive tumors. The 44 noncancer COPD controls, matched with the cancer cases for age, gender, and smoking habits, were negative for p53-Abs. These results indicate that p53-Abs may facilitate the early diagnosis of cancer in a subset of smokers with chronic obstructive pulmonary disease who are at an increased cancer risk.

A social gradient in fatal opioids and cocaine related overdoses?

PubMed

Origer, Alain; Le Bihan, Etienne; Baumann, Michèle

2015-01-01

To determine the existence of a social gradient in fatal overdose cases related to non-prescribed opioids and cocaine use, recorded in Luxembourg between 1994 and 2011. Overdose cases were individually matched with four controls in a nested case-control study design, according to sex, year of birth, drug administration route and duration of drug use. The study sample, composed of 272 cases and 1,056 controls, was stratified according to a Social Inequality Accumulation Score (SIAS), based on educational attainment, employment, income, financial situation of subjects and the professional status of their father or legal guardian. Least squares linear regression analysis on overdose mortality rates and ridit scores were applied to determine the Relative Index of Inequality (RII) of the study sample. A negative linear relationship between the overdose mortality rate and the relative socioeconomic position was observed. We found a difference in mortality of 29.22 overdose deaths per 100 drug users in the lowest socioeconomic group compared to the most advantaged group. In terms of the Relative Inequality Index, the overdose mortality rate of opioid and cocaine users with lowest socioeconomic profiles was 9.88 times as high as that of their peers from the highest socioeconomic group (95% CI 6.49-13.26). Our findings suggest the existence of a marked social gradient in opioids and cocaine related overdose fatalities. Harm reduction services should integrate socially supportive offers, not only because of their general aim of social (re)integration but crucially in order to meet their most important objective, that is to reduce drug-related mortality.

Obesity-related hormones and endometrial cancer among postmenopausal women: a nested case–control study within the B~FIT cohort

PubMed Central

Dallal, Cher M; Brinton, Louise A; Bauer, Douglas C; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; LaCroix, Andrea; Tice, Jeffrey A; Chia, Chia; Falk, Roni; Pfeiffer, Ruth; Pollak, Michael; Veenstra, Timothy D; Xu, Xia; Lacey, James V

2014-01-01

Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case–control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n = 15 595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992–1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m2), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (ORT3 vs T1 = 2.96; 95% CI, 1.21–7.25; P trend <0.01). After further adjustment for BMI, the estimates were attenuated and the positive trend was no longer statistically significant (ORT3 vs T1 = 2.11; 95% CI, 0.69–6.44; P trend = 0.18). No significant associations were observed with adiponectin or HMW adiponectin and endometrial cancer. Our findings with leptin suggest that the leptin–BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity–endometrial cancer associations. PMID:23222000

The obesity paradox in stable chronic heart failure does not persist after matching for indicators of disease severity and confounders.

PubMed

Frankenstein, Lutz; Zugck, Christian; Nelles, Manfred; Schellberg, Dieter; Katus, Hugo A; Remppis, B Andrew

2009-12-01

To verify whether controlling for indicators of disease severity and confounders represents a solution to the obesity paradox in chronic heart failure (CHF). From a cohort of 1790 patients, we formed 230 nested matched triplets by individually matching patients with body mass index (BMI) > 30 kg/m(2) (Group 3), BMI 20-24.9 k/m(2) (Group 1) and BMI 25-29.9 kg/m(2) (Group 2), according to NT-proBNP, age, sex, and NYHA class (triplet = one matched patient from each group). Although in the pre-matching cohort, BMI group was a significant univariable prognostic indicator, it did not retain significance [heart rate (HR): 0.91, 95% CI: 0.78-1.05, chi(2): 1.67] when controlled for group propensities as covariates. Furthermore, in the matched cohort, 1-year mortality and 3-year mortality did not differ significantly. Here, BMI again failed to reach statistical significance for prognosis, either as a continuous or categorical variable, whether crude or adjusted. This result was confirmed in the patients not selected for matching. NT-proBNP, however, remained statistically significant (log(NT-proBNP): HR: 1.49, 95% CI: 1.13-1.97, chi(2): 7.82) after multivariable adjustment. The obesity paradox does not appear to persist in a matched setting with respect to indicators of disease severity and other confounders. NT-proBNP remains an independent prognostic indicator of adverse outcome irrespective of obesity status.

A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants and the Risk of Hypospadias

PubMed Central

Rignell-Hydbom, Anna; Lindh, Christian H.; Dillner, Joakim; Jönsson, Bo A. G.; Rylander, Lars

2012-01-01

Background Environmental exposures to endocrine disrupting chemicals have been suggested as a risk factor for male genital abnormalities such as hypospadias. The aim of this case-control study was to investigate the association between fetal exposure to persistent organochlorine pollutants (POP) and the risk for hypospadias. Methodology/Principal Findings The Southern Sweden Maternity Cohort (SSMC) contains serum samples collected in early pregnancy among women in Southern Sweden. Linkages with the Medical Birth Register, the Malformation Register and the In-patient Register resulted in 390 SSMC mothers who had given birth to a boy with hypospadias in year 1986–2002 (mean 1995). For 237 of these (cases) sufficient amounts of serum for the chemical analyses were available. For each case, a control boy from the SSMC was randomly selected, matched for maternal age, birth year, parity and maternal smoking. PCB-153, p,p’-DDE and hexachlorbenzene (HCB) were used as biomarkers for POP exposure. The exposures were categorized into quartiles based on the distributions among the controls. There were no statistically significant trends between the a priori categorisation of the exposure variables and the risk for hypospadias. However, when the upper HCB quartile (>26 ng/ml) was compared to the other quartiles an odds ratio of 1.65 (95% CI 1.02 to 2.69) was obtained. p,p′-DDE levels above median (>1.0 ng/ml) compared to levels below 0.1 ng/ml gave an OR of 1.69 (95% CI 0.97 to 2.93). Conclusions The present study suggests that fetal exposure to HCB and p,p’-DDE may be a risk factor for hypospadias. PMID:23028613

The relationship between three-dimensional knee MRI bone shape and total knee replacement—a case control study: data from the Osteoarthritis Initiative

PubMed Central

Barr, Andrew J.; Dube, Bright; Hensor, Elizabeth M. A.; Kingsbury, Sarah R.; Peat, George; Bowes, Mike A.; Sharples, Linda D.

2016-01-01

Objective. There is growing understanding of the importance of bone in OA. Our aim was to determine the relationship between 3D MRI bone shape and total knee replacement (TKR). Methods. A nested case-control study within the Osteoarthritis Initiative cohort identified case knees with confirmed TKR for OA and controls that were matched using propensity scores. Active appearance modelling quantification of the bone shape of all knee bones identified vectors between knees having or not having OA. Vectors were scaled such that −1 and +1 represented the mean non-OA and mean OA shapes. Results. Compared to controls (n = 310), TKR cases (n = 310) had a more positive mean baseline 3D bone shape vector, indicating more advanced structural OA, for the femur [mean 0.98 vs −0.11; difference (95% CI) 1.10 (0.88, 1.31)], tibia [mean 0.86 vs −0.07; difference (95% CI) 0.94 (0.72, 1.16)] and patella [mean 0.95 vs 0.03; difference (95% CI) 0.92 (0.65, 1.20)]. Odds ratios (95% CI) for TKR per normalized unit of 3D bone shape vector for the femur, tibia and patella were: 1.85 (1.59, 2.16), 1.64 (1.42, 1.89) and 1.36 (1.22, 1.50), respectively, all P < 0.001. After including Kellgren–Lawrence grade in a multivariable analysis, only the femur 3D shape vector remained significantly associated with TKR [odds ratio 1.24 (1.02, 1.51)]. Conclusion. 3D bone shape was associated with the endpoint of this study, TKR, with femoral shape being most associated. This study contributes to the validation of quantitative MRI bone biomarkers for OA structure-modification trials. PMID:27185958

Low vitamin D status and suicide: a case-control study of active duty military service members.

PubMed

Umhau, John C; George, David T; Heaney, Robert P; Lewis, Michael D; Ursano, Robert J; Heilig, Markus; Hibbeln, Joseph R; Schwandt, Melanie L

2013-01-01

Considering that epidemiological studies show that suicide rates in many countries are highest in the spring when vitamin D status is lowest, and that low vitamin D status can affect brain function, we sought to evaluate if a low level of 25-hydroxyvitamin D [25(OH)D] could be a predisposing factor for suicide. We conducted a prospective, nested, case-control study using serum samples stored in the Department of Defense Serum Repository. Participants were previously deployed active duty US military personnel (2002-2008) who had a recent archived serum sample available for analysis. Vitamin D status was estimated by measuring 25(OH) D levels in serum samples drawn within 24 months of the suicide. Each verified suicide case (n = 495) was matched to a control (n = 495) by rank, age and sex. We calculated odds ratio of suicide associated with categorical levels (octiles) of 25(OH) D, adjusted by season of serum collection. More than 30% of all subjects had 25(OH)D values below 20 ng/mL. Although mean serum 25(OH)D concentrations did not differ between suicide cases and controls, risk estimates indicated that subjects in the lowest octile of season-adjusted 25(OH)D (<15.5 ng/mL) had the highest risk of suicide, with subjects in the subsequent higher octiles showing approximately the same level of decreased risk (combined odds ratio compared to lowest octile = 0.49; 95% C.I.: 0.315-0.768). Low vitamin D status is common in active duty service members. The lowest 25(OH)D levels are associated with an increased risk for suicide. Future studies could determine if additional sunlight exposure and vitamin D supplementation might reduce suicide by increasing 25(OH) D levels.

Parental and comorbid epilepsy in persons with bipolar disorder.

PubMed

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

2015-12-01

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

Bayesian Inference for the Stereotype Regression Model: Application to a Case-control Study of Prostate Cancer

PubMed Central

Ahn, Jaeil; Mukherjee, Bhramar; Banerjee, Mousumi; Cooney, Kathleen A.

2011-01-01

Summary The stereotype regression model for categorical outcomes, proposed by Anderson (1984) is nested between the baseline category logits and adjacent category logits model with proportional odds structure. The stereotype model is more parsimonious than the ordinary baseline-category (or multinomial logistic) model due to a product representation of the log odds-ratios in terms of a common parameter corresponding to each predictor and category specific scores. The model could be used for both ordered and unordered outcomes. For ordered outcomes, the stereotype model allows more flexibility than the popular proportional odds model in capturing highly subjective ordinal scaling which does not result from categorization of a single latent variable, but are inherently multidimensional in nature. As pointed out by Greenland (1994), an additional advantage of the stereotype model is that it provides unbiased and valid inference under outcome-stratified sampling as in case-control studies. In addition, for matched case-control studies, the stereotype model is amenable to classical conditional likelihood principle, whereas there is no reduction due to sufficiency under the proportional odds model. In spite of these attractive features, the model has been applied less, as there are issues with maximum likelihood estimation and likelihood based testing approaches due to non-linearity and lack of identifiability of the parameters. We present comprehensive Bayesian inference and model comparison procedure for this class of models as an alternative to the classical frequentist approach. We illustrate our methodology by analyzing data from The Flint Men’s Health Study, a case-control study of prostate cancer in African-American men aged 40 to 79 years. We use clinical staging of prostate cancer in terms of Tumors, Nodes and Metastatsis (TNM) as the categorical response of interest. PMID:19731262

Stomach Cancer Risk After Treatment for Hodgkin Lymphoma

PubMed Central

Morton, Lindsay M.; Dores, Graça M.; Curtis, Rochelle E.; Lynch, Charles F.; Stovall, Marilyn; Hall, Per; Gilbert, Ethel S.; Hodgson, David C.; Storm, Hans H.; Johannesen, Tom Børge; Smith, Susan A.; Weathers, Rita E.; Andersson, Michael; Fossa, Sophie D.; Hauptmann, Michael; Holowaty, Eric J.; Joensuu, Heikki; Kaijser, Magnus; Kleinerman, Ruth A.; Langmark, Frøydis; Pukkala, Eero; Vaalavirta, Leila; van den Belt-Dusebout, Alexandra W.; Fraumeni, Joseph F.; Travis, Lois B.; Aleman, Berthe M.; van Leeuwen, Flora E.

2013-01-01

Purpose Treatment-related stomach cancer is an important cause of morbidity and mortality among the growing number of Hodgkin lymphoma (HL) survivors, but risks associated with specific HL treatments are unclear. Patients and Methods We conducted an international case-control study of stomach cancer nested in a cohort of 19,882 HL survivors diagnosed from 1953 to 2003, including 89 cases and 190 matched controls. For each patient, we quantified cumulative doses of specific alkylating agents (AAs) and reconstructed radiation dose to the stomach tumor location. Results Stomach cancer risk increased with increasing radiation dose to the stomach (Ptrend < .001) and with increasing number of AA-containing chemotherapy cycles (Ptrend = .02). Patients who received both radiation to the stomach ≥ 25 Gy and high-dose procarbazine (≥ 5,600 mg/m2) had strikingly elevated stomach cancer risk (25 cases, two controls; odds ratio [OR], 77.5; 95% CI, 14.7 to 1452) compared with those who received radiation < 25 Gy and procarbazine < 5,600 mg/m2 (Pinteraction < .001). Risk was also elevated (OR, 2.8; 95% CI, 1.3 to 6.4) among patients who received radiation to the stomach ≥ 25 Gy but procarbazine < 5,600 mg/m2; however, no procarbazine-related risk was evident with radiation < 25 Gy. Treatment with dacarbazine also increased stomach cancer risk (12 cases, nine controls; OR, 8.8; 95% CI, 2.1 to 46.6), after adjustment for radiation and procarbazine doses. Conclusion Patients with HL who received subdiaphragmatic radiotherapy had dose-dependent increased risk of stomach cancer, with marked risks for patients who also received chemotherapy containing high-dose procarbazine. For current patients, risks and benefits of exposure to both procarbazine and subdiaphragmatic radiotherapy should be weighed carefully. For patients treated previously, GI symptoms should be evaluated promptly. PMID:23980092

Genetic variation in the ADIPOQ gene, adiponectin concentrations and risk of colorectal cancer: a Mendelian Randomization analysis using data from three large cohort studies.

PubMed

Nimptsch, Katharina; Song, Mingyang; Aleksandrova, Krasimira; Katsoulis, Michail; Freisling, Heinz; Jenab, Mazda; Gunter, Marc J; Tsilidis, Konstantinos K; Weiderpass, Elisabete; Bueno-De-Mesquita, H Bas; Chong, Dawn Q; Jensen, Majken K; Wu, Chunsen; Overvad, Kim; Kühn, Tilman; Barrdahl, Myrto; Melander, Olle; Jirström, Karin; Peeters, Petra H; Sieri, Sabina; Panico, Salvatore; Cross, Amanda J; Riboli, Elio; Van Guelpen, Bethany; Myte, Robin; Huerta, José María; Rodriguez-Barranco, Miguel; Quirós, José Ramón; Dorronsoro, Miren; Tjønneland, Anne; Olsen, Anja; Travis, Ruth; Boutron-Ruault, Marie-Christine; Carbonnel, Franck; Severi, Gianluca; Bonet, Catalina; Palli, Domenico; Janke, Jürgen; Lee, Young-Ae; Boeing, Heiner; Giovannucci, Edward L; Ogino, Shuji; Fuchs, Charles S; Rimm, Eric; Wu, Kana; Chan, Andrew T; Pischon, Tobias

2017-05-01

Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer.

Mitochondrial dysfunction in Gulf War illness revealed by 31Phosphorus Magnetic Resonance Spectroscopy: a case-control study.

PubMed

Koslik, Hayley J; Hamilton, Gavin; Golomb, Beatrice A

2014-01-01

Approximately 1/3 of 1990-1 Gulf War veterans developed chronic multisymptom health problems. Implicated exposures bear mechanisms that adversely affect mitochondria. Symptoms emphasize fatigue, cognition and muscle (brain and muscle are aerobically demanding); with protean additional domains affected, compatible with mitochondrial impairment. Recent evidence supports treatments targeting cell bioenergetics (coenzyme10) to benefit Gulf War illness symptoms. However, no evidence has directly documented mitochondrial or bioenergetic impairment in Gulf War illness. We sought to objectively assess for mitochondrial dysfunction, examining post-exercise phosphocreatine-recovery time constant (PCr-R) using (31)Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS), in Gulf War veterans with Gulf War illness compared to matched healthy controls. PCr-R has been described as a "robust and practical" index of mitochondrial status. Case-control study from 2012-2013. Fourteen community-dwelling Gulf War veterans and matched controls from the San Diego area comprised 7 men meeting CDC and Kansas criteria for Gulf War illness, and 7 non-deployed healthy controls matched 1:1 to cases on age, sex, and ethnicity. Calf muscle phosphocreatine was evaluated by (31)P-MRS at rest, through 5 minutes of foot pedal depression exercise, and in recovery, to assess PCr-R. Paired t-tests compared cases to matched controls. PCr-R was significantly prolonged in Gulf War illness cases vs their matched controls: control values, mean ± SD, 29.0 ± 8.7 seconds; case values 46.1 ± 18.0 seconds; difference 17.1 ± 14.9 seconds; p = 0.023. PCr-R was longer for cases relative to their matched controls for all but one pair; moreover while values clustered under 31 seconds for all but one control, they exceeded 35 seconds (with a spread up to 70 seconds) for all but one case. These data provide the first direct evidence supporting mitochondrial dysfunction in Gulf War illness. Findings merit replication in a larger study and/or corroboration with additional mitochondrial assessment tools.

Anti-Müllerian hormone and risk of ovarian cancer in nine cohorts.

PubMed

Jung, Seungyoun; Allen, Naomi; Arslan, Alan A; Baglietto, Laura; Barricarte, Aurelio; Brinton, Louise A; Egleston, Brian L; Falk, Roni T; Fortner, Renée T; Helzlsouer, Kathy J; Gao, Yutang; Idahl, Annika; Kaaks, Rudolph; Krogh, Vittorio; Merritt, Melissa A; Lundin, Eva; Onland-Moret, N Charlotte; Rinaldi, Sabina; Schock, Helena; Shu, Xiao-Ou; Sluss, Patrick M; Staats, Paul N; Sacerdote, Carlotta; Travis, Ruth C; Tjønneland, Anne; Trichopoulou, Antonia; Tworoger, Shelley S; Visvanathan, Kala; Weiderpass, Elisabete; Zeleniuch-Jacquotte, Anne; Dorgan, Joanne F

2018-01-15

Animal and experimental data suggest that anti-Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case-control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable-adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59-1.67) (P trend : 0.91). The association did not differ by age at blood draw or oral contraceptive use (all P heterogeneity : ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all P heterogeneity : ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer. © 2017 UICC.

Induced Abortions and the Risk of Preeclampsia Among Nulliparous Women

PubMed Central

Parker, Samantha E.; Gissler, Mika; Ananth, Cande V.; Werler, Martha M.

2015-01-01

Induced abortion (IA) has been associated with a lower risk of preeclampsia among nulliparous women, but it remains unclear whether this association differs by method (either surgical or medical) or timing of IA. We performed a nested case-control study of 12,650 preeclampsia cases and 50,600 matched control deliveries identified in the Medical Birth Register of Finland from 1996 to 2010. Data on number, method, and timing of IAs were obtained through a linkage with the Registry of Induced Abortions. Odds ratios and 95% confidence intervals were calculated. Overall, prior IA was associated with a lower risk of preeclampsia, with odds ratios of 0.9 (95% confidence interval (CI): 0.9, 1.0) for 1 prior IA and 0.7 (95% CI: 0.5, 1.0) for 3 or more IAs. Differences in the associations between IA and preeclampsia by timing and method of IA were small, with odds ratios of 0.8 (95% CI: 0.6, 1.1) for late (≥12 gestation weeks) surgical abortion and 0.9 (95% CI: 0.7, 1.2) for late medical abortion. There was no association between IA in combination with a history of spontaneous abortion and risk of preeclampsia. In conclusion, prior IA only was associated with a slight reduction in the risk of preeclampsia. PMID:26377957

Elevated Maternal C-Reactive Protein is Associated with Increased Risk of Schizophrenia in a National Birth Cohort

PubMed Central

Canetta, Sarah; Sourander, Andre; Surcel, Helja-Marja; Hinkka-Yli-Salomäki, Susanna; Leiviskä, Jaana; Kellendonk, Christoph; McKeague, Ian W.; Brown, Alan S.

2014-01-01

Objective The goal of the present study was to investigate an association between early gestational C-reactive protein (CRP), an established inflammatory biomarker, prospectively assayed in maternal sera, and schizophrenia in a large national birth cohort with an extensive serum biobank. Methods This study utilized a nested case-control design from the Finnish Prenatal Study of Schizophrenia cohort. 777 schizophrenia cases (630 with schizophrenia, 147 with schizoaffective disorder) that had maternal sera available for CRP testing were identified and matched to 777 controls in the analysis. Maternal CRP levels were assessed using a latex immunoassay from archived maternal serum specimens. Results Increasing maternal CRP levels, classified as a continuous variable, were significantly associated with schizophrenia in offspring (adjusted odds ratio (OR)=1.31, 95% confidence interval (CI)=1.10-1.56, p=0.003). This finding remained significant after adjusting for potential confounders including maternal and parental history of psychiatric disorders, twin/singleton birth, urbanicity, province of birth, and maternal socioeconomic status. Conclusion This finding provides the most robust evidence to date that maternal inflammation may play a significant role in schizophrenia, with possible implications for identifying preventive strategies and pathogenic mechanisms in schizophrenia and other neurodevelopmental disorders. PMID:24969261

Facilitators and barriers to employment among veterans with spinal cord injury receiving 12 months of evidence-based supported employment services.

PubMed

Cotner, Bridget A; Njoh, Eni N; Trainor, John K; O'Connor, Danielle R; Barnett, Scott D; Ottomanelli, Lisa

2015-01-01

Return to work is associated with positive rehabilitation outcomes for persons with spinal cord injury (SCI); however, more research is needed on vocational support for persons with disabilities seeking employment. The association between facilitators and barriers of employment and employment outcome was examined among Veterans with SCI who participated in an evidence-based supported employment (EBSE) program. Using a mixed-methods, nested case-control design, data on facilitators and barriers to employment were extracted from qualitative interviews and quantitative measures administered in person to 34 Veterans with SCI who completed 12 months of an EBSE program. Participants who did (case) and did not (control) obtain competitive employment were matched on time since SCI. Facilitators and barriers to employment were compared between the groups. Self-report measures administered at baseline were examined; there were no statistically significant factors that predicted employment outcomes after 12 months of EBSE program participation. Qualitative interview data revealed program-specific facilitators and Veteran characteristics that were associated with employment outcomes. Qualitative data illustrate how the integration of the vocational rehabilitation specialist on the medical team is helpful for addressing identified disability-specific barriers, including practical matters such as transportation and caregiving schedules, to facilitate employment outcomes.

Facilitators and Barriers to Employment Among Veterans with Spinal Cord Injury Receiving 12 Months of Evidence-Based Supported Employment Services

PubMed Central

Njoh, Eni N.; Trainor, John K.; O’Connor, Danielle R.; Barnett, Scott D.; Ottomanelli, Lisa

2015-01-01

Background: Return to work is associated with positive rehabilitation outcomes for persons with spinal cord injury (SCI); however, more research is needed on vocational support for persons with disabilities seeking employment. Objective: The association between facilitators and barriers of employment and employment outcome was examined among Veterans with SCI who participated in an evidence-based supported employment (EBSE) program. Methods: Using a mixed-methods, nested case-control design, data on facilitators and barriers to employment were extracted from qualitative interviews and quantitative measures administered in person to 34 Veterans with SCI who completed 12 months of an EBSE program. Participants who did (case) and did not (control) obtain competitive employment were matched on time since SCI. Facilitators and barriers to employment were compared between the groups. Results: Self-report measures administered at baseline were examined; there were no statistically significant factors that predicted employment outcomes after 12 months of EBSE program participation. Qualitative interview data revealed program-specific facilitators and Veteran characteristics that were associated with employment outcomes. Conclusions: Qualitative data illustrate how the integration of the vocational rehabilitation specialist on the medical team is helpful for addressing identified disability-specific barriers, including practical matters such as transportation and caregiving schedules, to facilitate employment outcomes. PMID:25762857

Personal and family medical history correlates of rheumatoid arthritis.

PubMed

de Roos, Anneclaire J; Cooper, Glinda S; Alavanja, Michael C; Sandler, Dale P

2008-06-01

Patients with rheumatoid arthritis (RA) often have comorbidities related to immune dysfunction, however, the timing of comorbidities relative to RA diagnosis and treatment is not clear. We studied personal and family medical history correlates of incident and prevalent RA in women. We used a nested case-control design including women in the Agricultural Health Study (AHS). Physician-confirmed cases of RA (n = 135) were matched to five controls each (n = 675) by birth date. We used logistic regression to examine associations between conditions listed in personal and family medical histories and both incident and prevalent RA, as estimated by odds ratios (ORs) and 95% confidence intervals (CIs). The risk of incident RA was associated with personal medical history of nonmelanoma skin cancer (OR = 4.4, 95% CI: 1.4-14.1), asthma or reactive lung disease (OR = 3.7, 95% CI: 1.3-10.5), and cataract (OR = 3.3, 95% CI: 1.0-10.8). Personal history of herpes zoster was associated with prevalent RA (OR = 2.4, 95% CI: 1.2-4.8), but not with incident RA. There were no consistent associations between family medical history and RA. Patients with medical conditions indicating compromised immunity are at increased risk of developing RA. These results may indicate common pathogenesis of an environmental or genetic nature between such diseases.

Urinary Biomarkers of Catechins and Risk of Hepatocellular Carcinoma in the Shanghai Cohort Study

PubMed Central

Butler, Lesley M.; Huang, Joyce Yongxu; Wang, Renwei; Lee, Mao-Jun; Yang, Chung S.; Gao, Yu-Tang; Yuan, Jian-Min

2015-01-01

Dietary catechins are phytochemicals with both antioxidative and prooxidative stress properties. Green tea is a major source of catechins and may be associated with hepatocellular carcinoma (HCC) risk, but the catechin-HCC relationship has not been evaluated using a biomarker-based approach. A nested case-control study of HCC (211 cases and 1,067 matched controls) was conducted within the Shanghai Cohort Study, which enrolled 18,244 men between 1986 and 1989. Concentrations of specific catechins, including epicatechin, epigallocatechin (EGC), and 4′-O-methyl-epigallocatechin, were measured in urine specimens that had been collected prior to HCC diagnosis. None of the catechins measured were associated with HCC risk. In stratified analyses, there was a statistically significant trend for an association of higher urinary EGC with increased HCC risk among subjects with positive serology for hepatitis B surface antigen (P for trend = 0.02). This positive EGC-HCC association became stronger for hepatitis B surface antigen–positive persons who also had low serum retinol levels (for detectable levels vs. undetectable levels, odds ratio = 2.62, 95% confidence interval: 1.25, 5.51). There was no evidence supporting a protective role of catechins in the development of HCC. Instead, exposure to high levels of catechins may increase the risk of developing HCC for high-risk individuals. PMID:25713334

A prospective evaluation of serum kynurenine metabolites and risk of pancreatic cancer.

PubMed

Huang, Joyce Y; Butler, Lesley M; Midttun, Øivind; Ulvik, Arve; Wang, Renwei; Jin, Aizhen; Gao, Yu-Tang; Ueland, Per M; Koh, Woon-Puay; Yuan, Jian-Min

2018-01-01

Serum pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, is associated with reduced risk of pancreatic cancer. Data on functional measures of vitamin B6 status and risk of pancreatic cancer is lacking. A nested case-control study involving 187 incident cases of pancreatic cancer and 362 individually matched controls were conducted within two prospective cohorts to evaluate the associations between kynurenine metabolites in pre-diagnostic serum samples and risk of pancreatic cancer. Higher serum concentrations of 3-hydroxyanthranilic acid (HAA) and the HAA:3-hydroxykynurenine (HK) ratio (a measure for in vivo functional status of PLP) were significantly associated with reduced risk of pancreatic cancer. Compared with the lowest tertile, odds ratios (95% confidence intervals) of pancreatic cancer for the highest tertile was 0.62 (0.39, 1.01) for HAA, and 0.59 (0.35-0.98) for the HAA:HK ratio, after adjustment for potential confounders and serum PLP (both Ps for trend<0.05). The kynurenine:tryptophan ratio or neopterin was not significantly associated with pancreatic cancer risk. The inverse association between HAA or the HAA:HK ratio and risk of pancreatic cancer supports the notion that functional status of PLP may be a more important measure than circulating PLP alone for the development of pancreatic cancer.

Spontaneous abortion in the British semiconductor industry: An HSE investigation. Health and Safety Executive.

PubMed

Elliott, R C; Jones, J R; McElvenny, D M; Pennington, M J; Northage, C; Clegg, T A; Clarke, S D; Hodgson, J T; Osman, J

1999-11-01

The UK Health and Safety Executive (HSE) conducted a study to examine the risk of spontaneous abortion (SAB) in British female semiconductor industry workers, following reports from the USA which suggested an association between risk of SAB and work in fabrication rooms and/or exposure to ethylene glycol ethers. A nested case-control study based on 2,207 women who had worked at eight manufacturing sites during a 5-year retrospective time frame was established; 36 cases were matched with 80 controls. The overall SAB rate in the industry was 10.0%. (65 SABs/651 pregnancies) The crude odds ratio (OR) for fabrication work was 0.65 (95% CI 0.30-1.40). This was essentially unchanged after adjustment for a range of potential confounding factors in the first 3 months of pregnancy and was reduced to 0.58 (95% CI 0.26-1.30) after adjustment for smoking in the previous 12 months. There were no statistically significantly elevated ORs for any work group or any specific chemical or physical exposure in the industry. There is no evidence of an increased risk of SAB in the British semiconductor industry. Am. J. Ind. Med. 36:557-572, 1999. Published 1999 Wiley-Liss, Inc.

Screening pharmaceuticals for possible carcinogenic effects: initial positive results for drugs not previously screened

PubMed Central

Friedman, Gary D.; Udaltsova, Natalia; Chan, James; Quesenberry, Charles P; Habel, Laurel A.

2010-01-01

Objective We screened commonly used prescription drugs for possible carcinogenic effects. Methods In a large health care program we identified 105 commonly used drugs, not previously screened. Recipients were followed for up to 12½ years for incident cancer. Nested case-control analyses of 55 cancer sites and all combined included up to ten matched controls per case, with lag of at least two years between drug dispensing and cancer. Positive associations entailed a relative risk (RR) of 1.50, with p≤ 0.01 and higher risk for three or more, than for one prescription. Evaluation included further analyses, searches of the literature, and clinical judgment. Results There were 101 associations of interest for 61 drugs. Sixty-six associations were judged to have involved substantial confounding. We found evidence that of the remaining 35, the following associations may not be due to chance: sulindac with gallbladder cancer and leukemia, hyoscyamine with non-Hodgkin lymphoma, nortriptyline with esophageal and hepatic cancer, oxazepam with lung cancer, both fluoxetine and paroxetine with testicular cancer, hydrochlorothiazide with renal and lip cancer, and nifedipine with lip cancer. Conclusions These preliminary findings suggest that further studies are indicated regarding sulindac, hyoscyamine, nortriptyline, oxazepam, fluoxetine, paroxetine, hydrochlorothiazide and nifedipine. PMID:19582585

An Algorithm for Creating Virtual Controls Using Integrated and Harmonized Longitudinal Data.

PubMed

Hansen, William B; Chen, Shyh-Huei; Saldana, Santiago; Ip, Edward H

2018-06-01

We introduce a strategy for creating virtual control groups-cases generated through computer algorithms that, when aggregated, may serve as experimental comparators where live controls are difficult to recruit, such as when programs are widely disseminated and randomization is not feasible. We integrated and harmonized data from eight archived longitudinal adolescent-focused data sets spanning the decades from 1980 to 2010. Collectively, these studies examined numerous psychosocial variables and assessed past 30-day alcohol, cigarette, and marijuana use. Additional treatment and control group data from two archived randomized control trials were used to test the virtual control algorithm. Both randomized controlled trials (RCTs) assessed intentions, normative beliefs, and values as well as past 30-day alcohol, cigarette, and marijuana use. We developed an algorithm that used percentile scores from the integrated data set to create age- and gender-specific latent psychosocial scores. The algorithm matched treatment case observed psychosocial scores at pretest to create a virtual control case that figuratively "matured" based on age-related changes, holding the virtual case's percentile constant. Virtual controls matched treatment case occurrence, eliminating differential attrition as a threat to validity. Virtual case substance use was estimated from the virtual case's latent psychosocial score using logistic regression coefficients derived from analyzing the treatment group. Averaging across virtual cases created group estimates of prevalence. Two criteria were established to evaluate the adequacy of virtual control cases: (1) virtual control group pretest drug prevalence rates should match those of the treatment group and (2) virtual control group patterns of drug prevalence over time should match live controls. The algorithm successfully matched pretest prevalence for both RCTs. Increases in prevalence were observed, although there were discrepancies between live and virtual control outcomes. This study provides an initial framework for creating virtual controls using a step-by-step procedure that can now be revised and validated using other prevention trial data.

Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort

PubMed Central

Escurriol, Verónica; Cofán, Montserrat; Moreno-Iribas, Concepción; Larrañaga, Nerea; Martínez, Carmen; Navarro, Carmen; Rodríguez, Laudina; González, Carlos A.; Corella, Dolores; Ros, Emilio

2010-01-01

Phytosterol intake with natural foods, a measure of healthy dietary choices, increases plasma levels, but increased plasma phytosterols are believed to be a coronary heart disease (CHD) risk factor. To address this paradox, we evaluated baseline risk factors, phytosterol intake, and plasma noncholesterol sterol levels in participants of a case control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort who developed CHD (n = 299) and matched controls (n = 584) who remained free of CHD after a 10 year follow-up. Sitosterol-to-cholesterol ratios increased across tertiles of phytosterol intake (P = 0.026). HDL-cholesterol level increased, and adiposity measures, cholesterol/HDL ratios, and levels of glucose, triglycerides, and lathosterol, a cholesterol synthesis marker, decreased across plasma sitosterol tertiles (P < 0.02; all). Compared with controls, cases had nonsignificantly lower median levels of phytosterol intake and plasma sitosterol. The multivariable-adjusted odds ratio for CHD across the lowest to highest plasma sitosterol tertile was 0.59 (95% confidence interval, 0.36–0.97). Associations were weaker for plasma campesterol. The apolipoprotein E genotype was unrelated to CHD risk or plasma phytosterols. The data suggest that plasma sitosterol levels are associated with a lower CHD risk while being markers of a lower cardiometabolic risk in the EPIC-Spain cohort, a population with a high phytosterol intake. PMID:19786566

Insulin use increases risk of asthma but metformin use reduces the risk in patients with diabetes in a Taiwanese population cohort.

PubMed

Chen, Chiung-Zuei; Hsu, Chih-Hui; Li, Chung-Yi; Hsiue, Tzuen-Ren

2017-12-01

Recent reports have suggested that insulin promotes airway smooth muscle contraction and enhances airway hyperresponsiveness, which are cardinal features of asthma. In contrast, metformin can reduce both airway inflammatory and remodeling properties. However, these results are all from in vitro and animal studies. This study investigated whether diabetes and various antidiabetic agents associate with the risk of asthma. We used a retrospective population-based cohort study using Taiwan's National Health Insurance claim database from 2000 to 2010 and a Cox proportional hazards regression model to compare the incidence of asthma between patients with diabetes (n = 19,428) and a matched non-diabetic group (n = 38,856). We also used a case-control study nested from the above cohort including 1,982 incident cases of asthma and 1,982 age- and sex-matched controls. A time density sampling technique was used to assess the effects of various antidiabetic agents on the risk of asthma. The incidence of asthma was significantly higher in the diabetic cohort than that in the non-diabetic cohort after adjustment for age, sex, and obesity, with a hazard ratio of 1.30 (95% confidence interval [CI]: 1.24-1.38). Insulin was found to increase the risk of asthma among diabetic patients (odds ratio [OR] 2.23; 95% CI: 1.52-3.58). In contrast, the use of metformin correlated with a decreased risk of asthma (OR 0.75; 95% CI: 0.60-0.95). Individuals with diabetes are at an increased risk of asthma. Insulin may further increase the risk of asthma, but the risk could possibly be reduced by using metformin.

Plasma Alkylresorcinols, Biomarkers of Whole-Grain Wheat and Rye Intake, and Incidence of Colorectal Cancer

PubMed Central

2014-01-01

Background Few studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations. Methods The association between alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal cancer incidence were investigated using prediagnostic plasma samples from colorectal cancer case patients and matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We included 1372 incident colorectal cancer case patients and 1372 individual matched control subjects and calculated the incidence rate ratios (IRRs) for overall and anatomical subsites of colorectal cancer using conditional logistic regression adjusted for potential confounders. Regional differences (Scandinavia, the Mediterranean, Central Europe) were also explored. Results High plasma total alkylresorcinol concentration was associated with lower incidence of distal colon cancer; the adjusted incidence rate ratio of distal colon cancer for the highest vs lowest quartile of plasma total alkylresorcinols was 0.48 (95% confidence interval [CI] = 0.28 to 0.83). An inverse association between plasma total alkylresorcinol concentrations and colon cancer was found for Scandinavian participants (IRR per doubling = 0.83; 95% CI = 0.70 to 0.98). However, plasma total alkylresorcinol concentrations were not associated with overall colorectal cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols concentrations were associated with colon and distal colon cancer only in Central Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher). Conclusions High concentrations of plasma alkylresorcinols were associated with a lower incidence of distal colon cancer but not with overall colorectal cancer, proximal colon cancer, and rectal cancer. PMID:24317181

Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

PubMed

Agudo, Antonio; Bonet, Catalina; Sala, Núria; Muñoz, Xavier; Aranda, Núria; Fonseca-Nunes, Ana; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie Christine; Vineis, Paolo; Panico, Salvatore; Palli, Domenico; Tumino, Rosario; Grioni, Sara; Quirós, J Ramón; Molina, Esther; Navarro, Carmen; Barricarte, Aurelio; Chamosa, Saioa; Allen, Naomi E; Khaw, Kay-Tee; Bueno-de-Mesquita, H Bas; Siersema, Peter D; Numans, Mattijs E; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Kaaks, Rudof; Canzian, Federico; Boeing, Heiner; Meidtner, Karina; Johansson, Mattias; Sund, Malin; Manjer, Jonas; Overvad, Kim; Tjonneland, Anne; Lund, Eiliv; Weiderpass, Elisabete; Jenab, Mazda; Fedirko, Veronika; Offerhaus, G Johan A; Riboli, Elio; González, Carlos A; Jakszyn, Paula

2013-06-01

Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.

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.

Current and past Epstein-Barr virus infection in risk of initial CNS demyelination.

PubMed

Lucas, R M; Ponsonby, A-L; Dear, K; Valery, P; Pender, M P; Burrows, J M; Burrows, S R; Chapman, C; Coulthard, A; Dwyer, D E; Dwyer, T; Kilpatrick, T; Lay, M-L J; McMichael, A J; Taylor, B V; van der Mei, I A F; Williams, D

2011-07-26

To assess risk of a first clinical diagnosis of CNS demyelination (FCD) in relation to measures of Epstein-Barr virus (EBV) infection within the context of other known risk factors. This was a multicenter incident case-control study. FCD cases (n = 282) aged 18-59 years and controls (n = 558, matched on age, sex, and region) were recruited from 4 Australian centers between November 1, 2003, and December 31, 2006. A nested study (n = 215 cases, n = 216 controls) included measurement of whole blood quantitative EBV DNA load and serum EBV-specific antibodies. Conditional logistic regression was used to analyze case-control differences. There were no significant case-control differences in the proportion with detectable EBV DNA (55.8% vs 50.5%, respectively, p = 0.28), or in quantitative EBV DNA load (p = 0.33). Consistent with previous work, higher anti-EBV-specific immunoglobulin G (IgG) titers and a history of infectious mononucleosis were associated with increased FCD risk and there was an additive interaction with HLA-DRB1*1501 status. We found additional interactions between high anti-EBNA IgG titer and SNPs in HLA-A (adjusted odds ratios [AOR] = 19.84 [95% confidence interval (CI) 5.95 to 66.21] for both factors compared to neither) and CTLA-4 genes (AOR = 0.31 [95% CI 0.13 to 0.76] for neither factor compared to both). EBV DNA load was lower at higher serum 25-hydroxyvitamin D concentrations in controls (r = -0.17, p = 0.01). An adverse effect of higher EBV DNA load on FCD risk was increased with higher 25-hydroxyvitamin D concentration (p[interaction] = 0.02). Past infection with EBV, but not current EBV DNA load in whole blood, is significantly associated with increased FCD risk. These associations appear to be modified by immune-related gene variants.

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.

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

PubMed

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

2015-05-01

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

Prevalence of non-organ-specific autoantibodies and chronic liver disease in the general population: a nested case-control study of the Dionysos cohort.

PubMed

Lenzi, M; Bellentani, S; Saccoccio, G; Muratori, P; Masutti, F; Muratori, L; Cassani, F; Bianchi, F B; Tiribelli, C

1999-09-01

Several retrospective and prospective studies report an increased prevalence of non-organ-specific autoantibodies (NOSAs) in patients with hepatitis C virus (HCV) related chronic liver disease (CLD). Some of the data so far available are controversial and the true prevalence of NOSAs in the general population is still not known. To explore the prevalence of NOSAs, their relation to different HCV genotypes, and the presence and severity of CLD in the general population of Northern Italy. All 226 anti-HCV positive and 87 hepatitis B surface antigen (HBsAg) positive patients of the Dionysos cohort study were analysed and compared with sex and age matched cases (226) negative for both anti-HCV antibody and HBsAg selected from the same cohort. Sera tested for the presence of NOSAs (anti-nuclear antibody (ANA), anti-smooth muscle antibody (SMA), and anti-liver/kidney microsomes type 1 antibody (LKM1)) were screened by indirect immunofluorescence at a 1:40 serum dilution. HCV RNA and HCV genotypes were also determined by nested polymerase chain reaction (PCR) of the 5' non-coding region and by PCR amplification of the core region with type specific primers. The overall prevalence of NOSA reactivity was significantly higher in anti-HCV positive subjects than in both normal and pathological controls (25% v 6% and 7% respectively, p<0.05). ANA, SMA, and LKM1 occurred in 16, 10, and 1. 3% of cases respectively. No specific association between NOSAs and a specific HCV genotype was found. NOSAs were found more often associated with more than one genotype (35.7%) and with untypable genotypes (34.6%), although the association was not statistically significant. NOSAs were associated with HCV RNA and CLD but not with the presence of cirrhosis and/or hepatocellular carcinoma. On univariate analysis, NOSA reactivity was independently associated with abnormal alanine aminotransferase (p<0.01) and gamma-glutamyltranspeptidase levels (p<0.05). The risk for the presence of NOSAs was 5.1 times higher in anti-HCV subjects than in controls. In the general population the prevalence of NOSAs is higher in anti-HCV positive subjects than in normal or disease controls. Moreover NOSAs are associated with CLD and with a more active disease in terms of alanine aminotransferase activity.

Plasma cytokine profiles in HIV-1 infected patients developing neuropathic symptoms shortly after commencing antiretroviral therapy: a case-control study.

PubMed

Van der Watt, Johan J; Wilkinson, Katalin A; Wilkinson, Robert J; Heckmann, Jeannine M

2014-02-10

In patients infected with human immunodeficiency virus 1 (HIV-1) neuropathic symptoms may develop within weeks of starting combination antiretroviral therapy (cART). This timing coincides with the occurrence of immune reconstitution inflammatory syndrome. Our objective was to investigate the longitudinal association of plasma cytokine and soluble receptor concentrations with incident neuropathic symptoms within 12 weeks of starting programme-based cART in a nested case-control study. One hundred and twenty adults without neuropathic symptoms and about to initiate cART were followed longitudinally for 24 weeks after cART initiation. Subjects were examined for peripheral neuropathy at baseline (pre-cART) and 2-, 4-, 12- and 24 weeks thereafter. Individuals developing neuropathic symptoms within 12 weeks of starting cART were matched in a nested case-control design with those remaining symptom-free for at least 24 weeks. Plasma was collected at each visit. Cytokines and soluble receptors were quantified using multiplex immunometric assays. Incident neuropathic symptoms occurred in 32 (27%) individuals within 12 weeks of starting cART for the first time. Cytokine concentrations increased at 2 weeks, irrespective of symptom-status, returning to baseline concentrations at 12 weeks. Compared to the control group, the symptomatic group had higher baseline levels of interleukin-1 receptor (IL-1R)-antagonist. The symptomatic group also showed greater increases in soluble interleukin-2 receptor-alpha and tumour necrosis factor (TNF) receptor-II levels at week 2 and soluble interleukin-6 receptor levels at week 12. Ratios of pro-inflammatory- vs anti-inflammatory cytokines were higher for TNF-alpha/IL-4 (p = 0.022) and interferon-gamma/IL-10 (p = 0.044) in those developing symptoms. After 24 weeks of cART, the symptomatic group showed higher CD4+ counts (p = 0.002). The initiation of cART in previously treatment naïve individuals was associated with a cytokine 'burst' between 2- and 4 weeks compared with pre-cART levels. Individuals developing neuropathic symptoms within 12 weeks of starting cART showed evidence of altered cytokine concentrations even prior to initiating cART, most notably higher circulating IL-1R-antagonist levels, and altered ratios of "pain-associated" cytokine and soluble receptors shortly after cART initiation.

Vitamin D and the risk of preeclampsia--a nested case-control study.

PubMed

Gidlöf, Sebastian; Silva, Aldo T; Gustafsson, Sven; Lindqvist, Pelle G

2015-08-01

We aimed to determine the relation between vitamin D deficiency in early pregnancy and preeclampsia. In a nested case-control study of 2496 pregnant women, we identified 39 women who developed preeclampsia and 120 non-preeclamptic controls. Blood was sampled in 12th gestational week and analyzed for serum vitamin D. Vitamin D levels were similar in women who developed preeclampsia, 52.2 ± 20.5 nmol/L, and controls, 48.6 ± 20.5 nmol/L, p = 0.3. In addition, vitamin D deficiency (<50 nmol/L) was found in a similar proportion of control group (51.7%) as those with severe preeclampsia (41.2%). Women with vitamin D deficiency were 3 cm shorter than those with normal vitamin D levels (p = 0.002). Our data do not support the hypothesis that vitamin D deficiency in early pregnancy is associated with preeclampsia, but we cannot rule out a relation later in gestation. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Cutaneous beta human papillomaviruses and the development of male external genital lesions: A case-control study nested within the HIM Study.

PubMed

Pierce Campbell, Christine M; Gheit, Tarik; Tommasino, Massimo; Lin, Hui-Yi; Torres, B Nelson; Messina, Jane L; Stoler, Mark H; Rollison, Dana E; Sirak, Bradley A; Abrahamsen, Martha; Carvalho da Silva, Roberto J; Sichero, Laura; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

2016-10-01

Cutaneous human papillomaviruses (HPVs) increase the risk of non-melanoma skin cancer in sun-exposed skin. We examined the role of beta-HPV in the development of male external genital lesions (EGLs), a sun-unexposed site. In this nested case-control study (67 men with pathologically-confirmed EGLs and 134 controls), exfoliated cells collected from the surface of lesions and normal genital skin 0, 6, and 12 months preceding EGL development were tested for beta-HPV DNA using a type-specific multiplex genotyping assay. Beta-HPV prevalence was estimated and conditional logistic regression was used to evaluate the association with condyloma, the most common EGL. While beta-HPV prevalence among controls remained stable, the prevalence among cases was lowest on the surface of lesion. Detecting beta-HPV on the normal genital skin was not associated with the presence or development of condyloma. Cutaneous beta-HPV does not appear to be contributing to pathogenesis in male genital skin. Copyright © 2016. Published by Elsevier Inc.

A Step-by-Step Guide to Propensity Score Matching in R

ERIC Educational Resources Information Center

Randolph, Justus J.; Falbe, Kristina; Manuel, Austin Kureethara; Balloun, Joseph L.

2014-01-01

Propensity score matching is a statistical technique in which a treatment case is matched with one or more control cases based on each case's propensity score. This matching can help strengthen causal arguments in quasi-experimental and observational studies by reducing selection bias. In this article we concentrate on how to conduct propensity…

Myeloid leukaemia in systemic lupus erythematosus--a nested case-control study based on Swedish registers.

PubMed

Löfström, Björn; Backlin, Carin; Sundström, Christer; Hellström-Lindberg, Eva; Ekbom, Anders; Lundberg, Ingrid E

2009-10-01

To assess the risk factors for leukaemic transformation and myeloid leukaemia in patients with SLE. A national SLE cohort identified through SLE discharge diagnoses in the Swedish hospital discharge register during 1964 to 1995 (n = 6438) was linked to the national cancer register. A nested case-control study in SLE patients who developed acute or chronic myeloid leukaemia was performed with SLE patients without malignancy as controls. Medical records from cases and controls were reviewed and bone marrow specimens were re-evaluated. A Medline search of previously published cases of SLE and myeloid leukaemia was performed. After confirmation of SLE diagnosis according to the ACR criteria, eight patients with SLE and myeloid leukaemia and 18 SLE controls were included in the study. Preceding leucopenia was significantly associated with leukaemia development, whereas other SLE manifestations were not. Two cases had a preceding bone marrow confirming myelodysplastic syndrome (MDS). Only two cases were significantly treated with cyclophosphamide or AZA. A Medline search resulted in only 15 previously published cases of coincident SLE and myeloid leukaemia. Preceding MDS was reported in five of these, whereas only eight had been treated with cytotoxic drugs. Low-dose chemotherapy was not a major cause of myeloid malignancy in our population-based cohort of SLE patients nor in the reported cases from literature. Leucopenia was a risk factor for myeloid leukaemia development and an MDS was frequently seen. Therefore bone marrow investigation should be considered in SLE patients with long-standing leucopenia and anaemia.

Investigation to identify a resource-efficient case-control methodology for determining antibiotics associated with Clostridium difficile infection.

PubMed

Chung, Philip; Currie, Brian; Guo, Yi; Talansky, Moshe; Brown, Shakara; Ostrowsky, Belinda

2014-10-01

Antimicrobial exposure remains an important risk factor for developing Clostridium difficile infection (CDI). Efficient method to identify antibiotics associated with CDI is important for formulating strategies to curtail their use. As a prelude to a more extensive Agency for Healthcare Research and Quality-funded project (Evaluation & Research on Antimicrobial Stewardship's Effect on Clostridium difficile), we undertook an exploratory evaluation to determine a resource-efficient method for identifying antibiotic targets for antimicrobial stewardship interventions. The study compared a series of 6 focused case-control studies. Cases consisted of patients with laboratory-confirmed CDI admitted from July-October 2009. Controls were selected from patients without CDI hospitalized during the same period. Five groups of controls were matched to cases (2:1 ratio) using group-specific matching criteria, including admission date, age, type of admission, length of stay (LOS) to discharge, and/or LOS to CDI diagnosis. The final control group was selected from patients who received antibiotics during hospitalization. Data, including demographics and antibiotic usage, were compared between case and control groups. A total of 126 cases were matched to 6 groups of 252 controls. For control groups 1-5, the use of piperacillin and tazobactam, ceftriaxone or cefepime, ciprofloxacin or moxifloxacin, intravenous vancomycin, azithromycin, and antibiotics of last resort were significantly more frequent in case than control patients. For the final control group, the associations between ceftriaxone or cefepime, and ciprofloxacin or moxifloxacin use and CDI no longer persisted. This could in part be explained by differences in comorbidities between case and control patients even with stringent matching criteria. Use of a simple matching strategy to conduct case-control studies is an efficient and feasible compromise strategy, especially in resource-limited settings, to identify high-risk antibiotics associated with CDI. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Network-based regularization for matched case-control analysis of high-dimensional DNA methylation data.

PubMed

Sun, Hokeun; Wang, Shuang

2013-05-30

The matched case-control designs are commonly used to control for potential confounding factors in genetic epidemiology studies especially epigenetic studies with DNA methylation. Compared with unmatched case-control studies with high-dimensional genomic or epigenetic data, there have been few variable selection methods for matched sets. In an earlier paper, we proposed the penalized logistic regression model for the analysis of unmatched DNA methylation data using a network-based penalty. However, for popularly applied matched designs in epigenetic studies that compare DNA methylation between tumor and adjacent non-tumor tissues or between pre-treatment and post-treatment conditions, applying ordinary logistic regression ignoring matching is known to bring serious bias in estimation. In this paper, we developed a penalized conditional logistic model using the network-based penalty that encourages a grouping effect of (1) linked Cytosine-phosphate-Guanine (CpG) sites within a gene or (2) linked genes within a genetic pathway for analysis of matched DNA methylation data. In our simulation studies, we demonstrated the superiority of using conditional logistic model over unconditional logistic model in high-dimensional variable selection problems for matched case-control data. We further investigated the benefits of utilizing biological group or graph information for matched case-control data. We applied the proposed method to a genome-wide DNA methylation study on hepatocellular carcinoma (HCC) where we investigated the DNA methylation levels of tumor and adjacent non-tumor tissues from HCC patients by using the Illumina Infinium HumanMethylation27 Beadchip. Several new CpG sites and genes known to be related to HCC were identified but were missed by the standard method in the original paper. Copyright © 2012 John Wiley & Sons, Ltd.

Effects of Gluten Intake on Risk of Celiac Disease: A Case-Control Study on a Swedish Birth Cohort.

PubMed

Andrén Aronsson, Carin; Lee, Hye-Seung; Koletzko, Sibylle; Uusitalo, Ulla; Yang, Jimin; Virtanen, Suvi M; Liu, Edwin; Lernmark, Åke; Norris, Jill M; Agardh, Daniel

2016-03-01

Early nutrition may affect the risk of celiac disease. We investigated whether amount of gluten in diet until 2 years of age increases risk for celiac disease. We performed a 1-to-3 nested case-control study of 146 cases, resulting in 436 case-control pairs matched for sex, birth year, and HLA genotype generated from Swedish children at genetic risk for celiac disease. Newborns were annually screened for tissue transglutaminase autoantibodies (tTGA). If tested tTGA positive, time point of seroconversion was determined from frozen serum samples taken every 3 months. Celiac disease was confirmed by intestinal biopsies. Gluten intake was calculated from 3-day food records collected at ages 9, 12, 18 and 24 months. Odds ratios (OR) were calculated through conditional logistic regression. Breastfeeding duration (median, 32 wk) and age at first introduction to gluten (median, 22 wk) did not differ between cases and tTGA-negative controls. At the visit before tTGA seroconversion, cases reported a larger intake of gluten than controls (OR, 1.28; 95% confidence interval [CI], 1.13-1.46; P = .0002). More cases than controls were found in the upper third tertile (ie, >5.0 g/d) before they tested positive for tTGA seroconversion than controls (OR, 2.65; 95% CI, 1.70-4.13; P < .0001). This finding was similar in children homozygous for DR3-DQ2 (OR, 3.19; 95% CI, 1.61-6.30; P = .001), heterozygous for DR3-DQ2 (OR, 2.24; 95% CI, 1.08-4.62; P = .030), and for children not carrying DR3-DQ2 (OR, 2.43; 95% CI, 0.90-6.54; P = .079). The amount of gluten consumed until 2 years of age increases the risk of celiac disease at least 2-fold in genetically susceptible children. These findings may be taken into account for future infant feeding recommendations. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Plasma Enterolactone and Breast Cancer Risk in the Nurses’ Health Study II

PubMed Central

Xie, Jing; Tworoger, Shelley S.; Franke, Adrian A.; Terry, Kathryn L.; Rice, Megan S.; Rosner, Bernard A.; Willett, Walter C.; Hankinson, Susan E.; Eliassen, A. Heather

2013-01-01

Background Lignans are plant-based phytoestrogens with both estrogenic and anti-estrogenic properties that may be important for breast carcinogenesis. Retrospective studies have observed decreased breast cancer risk associated with high circulating enterolactone concentrations, a biomarker of lignan intake, but results from prospective studies are conflicting. Methods To prospectively examine this association, we measured plasma enterolactone levels in 802 breast cancer cases and 802 matched controls nested among predominantly premenopausal women in the Nurses’ Health Study II (NHSII) cohort. We used conditional logistic regression and polytomous logistic regression models, adjusting for known breast cancer risk factors, to calculate relative risks (RR) and 95% confidence intervals (CI). Results Compared to women with enterolactone concentrations ≤ 4nmol/L, the multivariate adjusted RRs for breast cancer were 1.18 (95% CI: 0.86–1.62), 0.91 (95% CI: 0.66–1.25), and 0.96 (95% CI: 0.70–1.33) for women with enterolactone levels in the 2nd to the 4th quartiles, respectively; Ptrend=0.60. Results were similar across tumors defined by estrogen and progesterone receptor status. Among premenopausal women with follicular estradiol levels below the median (<47 pg/mL), women in the highest category of enterolactone levels had a 51% lower breast cancer risk compared to those in the lowest category (95% CI: 0.27–0.91); Ptrend=0.02. No association was observed among women with high follicular estradiol levels (≥47 pg/mL), (comparable RR=1.39, 95% CI: 0.73–2.65; Pinteraction=0.02). Conclusions We did not observe an overall association between plasma enterolactone and breast cancer risk in a large nested case-control study of US women. However, a significant inverse association was observed among premenopausal women with low follicular estradiol levels, suggesting that enterolactone may be important in a low estrogen environment. This should be confirmed in future studies. PMID:23760859

Prevalence of Hyperkalemia in Diabetic and Non-Diabetic Patients with Chronic Kidney Disease: A Nested Case-Control Study.

PubMed

Loutradis, Charalampos; Tolika, Panagiota; Skodra, Alexandra; Avdelidou, Afroditi; Sarafidis, Pantelis A

2015-01-01

Hyperkalemia is a potentially life-threatening disorder, usually complicating chronic kidney disease (CKD). Factors superimposed to reduced renal function are further elevating hyperkalemia risk, but their contribution is not fully elucidated. This study aimed to compare the prevalence of hyperkalemia in diabetic and non-diabetic patients with CKD. This is a nested case-control study of 180 type-2 diabetic and 180 non-diabetic patients with CKD followed in a Nephrology outpatient clinic, matched for gender, age and estimated glomerular filtration rate. Type-1 diabetes or end-stage renal disease patients were excluded. Prevalence of hyperkalemia was defined as potassium >5 mEq/l or use of sodium polystyrene sulfonate, and further by potassium >5, ≥5.2 and ≥5.5 mEq/l. It was calculated in both groups in whole and CKD stages separately. Univariate and multivariate logistic regression analysis were conducted to identify factors associated with hyperkalemia. The prevalence of hyperkalemia was higher in diabetic CKD patients (27.2 vs. 20%, p = 0.107) and remained around 30% higher with all secondary definitions used, but never reached statistical significance. In Stage 2, no difference was noted (8.7 vs. 17.4%, p = 0.665); in Stage 3, it was significantly higher in diabetics (28.6 vs. 17.5%, p = 0.036); and in Stage 4, it was equally high in both groups (35.5 vs. 32.3%, p = 0.788). In multivariate analysis, Stage 4 CKD (OR 4.535, 95% CI 1.561-13.173), use of angiotensin-converting enzyme inhibitors (ACEIs; OR 2.228, 95% CI 1.254-3.958) and smoking (OR 2.254, 95% CI 1.218-4.171) were independently associated with hyperkalemia. Diabetes mellitus was found to elevate the prevalence of hyperkalemia only in CKD Stage 3 patients (moderately impaired renal function). Advanced CKD at Stage 4 and ACEIs are major determinants of hyperkalemia occurrence. © 2015 S. Karger AG, Basel.

Exploring the links between water, sanitation and hygiene and disability; Results from a case-control study in Guatemala.

PubMed

Kuper, Hannah; Mactaggart, Islay; White, Sian; Dionicio, Carlos; Cañas, Rafael; Naber, Jonathan; Polack, Sarah; Biran, Adam

2018-01-01

To assess the Water, Sanitation and Hygiene (WASH) access and appropriateness of people with disabilities compared to those without, in Guatemala. A case-control study was conducted, nested within a national survey. The study included 707 people with disabilities, and 465 age- and sex-matched controls without disabilities. Participants reported on WASH access at the household and individual level. A sub-set of 121 cases and 104 controls completed a newly designed, in-depth WASH questionnaire. Households including people with disabilities were more likely to use an improved sanitation facility compared to control households (age-sex-adjusted OR: 1.7, 95% CI 1.3-2.5), but otherwise there were no differences in WASH access at the household level. At the individual level, people with disabilities reported greater difficulties in relation to sanitation (mean score 26.2, SD 26.5) and hygiene access and quality (mean 30.7, SD 24.2) compared to those without disabilities (15.5, 21.7, p<0.001; 22.4, 19.1, p<0.01). There were no differences in different aspects of water collection between people with and without disabilities in this context where over 85% of participants had water piped into their dwelling. Among people with disabilities, older adults were more likely to experience difficulties in hygiene and sanitation than younger people with disabilities. People with disabilities in Guatemala experience greater difficulties in accessing sanitation facilities and practicing hygienic behaviours than their peers without disabilities. More data collection is needed using detailed tools to detect these differences, highlight which interventions are needed, and to allow assessment of their effectiveness.

Exposure assessment for a nested case-control study of lung cancer among European asphalt workers.

PubMed

Agostini, Michela; Ferro, Gilles; Olsson, Ann; Burstyn, Igor; De Vocht, Frank; Hansen, Johnni; Lassen, Christina Funch; Johansen, Christoffer; Kjaerheim, Kristina; Langard, Sverre; Stucker, Isabelle; Ahrens, Wolfgang; Behrens, Thomas; Lindbohm, Marja-Liisa; Heikkilä, Pirjo; Heederik, Dick; Portengen, Lützen; Shaham, Judith; Boffetta, Paolo; Kromhout, Hans

2010-10-01

Development of a method for retrospective assessment of exposure to bitumen fume, bitumen condensate, organic vapour, polycyclic aromatic hydrocarbons, and co-exposures to known or suspected lung carcinogens for a nested case-control study of lung cancer mortality among European asphalt workers. Company questionnaires and structured questionnaires used in interviews and industry-specific job-exposure matrices (JEMs) were elaborated and applied. Three sources of information were eventually used for exposure assessment and assignment: (i) data obtained in cohort phase, (ii) data from living subjects, next-of-kin, and fellow-workers questionnaires, and (iii) JEMs for bitumen exposure by inhalation and via skin and co-exposures to known or suspected lung carcinogens within and outside cohort companies. Inhalation and dermal exposure estimates for bitumen were adjusted for time trends, time spent in a job, and other determinants of exposure (e.g. oil gravel paving). Clothing patterns, personal protective devices, and personal hygiene were taken into consideration while estimating dermal exposure. Occupational exposures could be assessed for 433 cases and 1253 controls for relevant time periods. Only 43% of work histories were spent inside original asphalt and construction companies. A total of 95.8% of job periods in cohort companies could be coded at a more detailed level. Imputation of work time and 'hygienic behaviour' multipliers was needed for <10% of work history years. Overall, downward trends in exposure were present and differences existed between countries and companies. As expected, correlations were strongest (r > 0.7) among bitumen-related agents, while correlations between coal tar, bitumen-related agents, and established lung carcinogens were weaker (r < 0.4). A systematic and detailed approach was developed to estimate inhalation and dermal exposure for a nested case-control study among asphalt workers.

Allergy is associated with suicide completion with a possible mediating role of mood disorder - a population-based study.

PubMed

Qin, P; Mortensen, P B; Waltoft, B L; Postolache, T T

2011-05-01

With increasing research suggesting a role of allergy on suicidality, this study, on a population level, delved into how allergy affects risk for suicide completion in the context of mood disorder and other factors. Based on the entire population of Denmark, we included 27,096 completed suicides and 467,571 live controls matched on sex and age with a nested case-control design. We retrieved personal information on hospital contacts for allergy and other variables from various Danish longitudinal registries and analyzed the data with conditional logistic regression. We noted that 1.17% suicide victims, compared with 0.79% matched controls, had a history of hospital contact for allergy and that a history of allergy predicted an increased risk for suicide completion; however, the effect was confined to allergy that led to inpatient treatment (IRR: 1.59, 95% CI: 1.41-1.80). The increased risk was attenuated somewhat but remained significant when adjusted for personal psychiatric history and socioeconomic status. Meanwhile, we observed a nonsignificantly stronger effect in women than in men, and a significant age difference with a stronger effect for individuals at high ages. Moreover, we detected a significant interaction between allergy and mood disorder - even an antagonism effect of the two exposures. Allergy increased suicide risk only in persons with no history of mood disorder, whereas it eliminated suicide risk in those with a history of mood disorder. The findings support a link between allergy and suicidality, with a possible mediating role of mood disorder. © 2010 John Wiley & Sons A/S.

Associated injuries, management, and outcomes of blunt abdominal aortic injury.

PubMed

de Mestral, Charles; Dueck, Andrew D; Gomez, David; Haas, Barbara; Nathens, Avery B

2012-09-01

Blunt abdominal aortic injury (BAAI) is very rare, and current literature is limited to case series of single-center experience. Through an analysis of the National Trauma Data Bank, the largest aggregation of United States trauma registry data, our aim was to characterize the associated injury pattern, contemporary management, and in-hospital outcomes of patients with BAAI. We used a nested case-control design. The overall cohort consisted of adult patients (age ≥ 16 years) severely injured (Injury Severity Score ≥ 16) after blunt trauma who were treated at a level 1 or 2 trauma center in years 2007 to 2009. Cases were patients with BAAI and were frequency-matched by age group and mechanism to randomly selected controls at a one-to-five ratio. Multivariable matched analysis (conditional logistic regression) was used to derive adjusted measures of association between BAAI and adjacent arterial, intra-abdominal, and bony injuries. We identified 436 patients with BAAI from 180 centers. The mean Injury Severity Score was 35 ± 14, and most patients were injured in motor vehicle crashes (84%). Multivariable analysis showed injury to the thoracic aorta, renal and iliac artery, small bowel, colon, liver, pancreas, and kidney, as well as lumbar spine fractures were independently associated with BAAI. A total of 394 patients (90%) were managed nonoperatively, and 42 (10%) underwent repair. Of these 42 patients, 29 (69%) underwent endovascular repair, with 11 patients undergoing open aortic repair and two extra-anatomic bypasses. Median time from admission to repair was 1 day (interquartile range, 1-2 days). Overall mortality was 29%. A total of 271 (69%) patients managed nonoperatively survived to hospital discharge. The index of suspicion for BAAI should be raised in severely injured patients by the presence of injuries to the lumbar spine, bowel, retroperitoneal organs, and adjacent major arteries. Although endovascular repair is the most common intervention, most patients are managed nonoperatively and survive to hospital discharge. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Cytochrome P450 2E1 gene polymorphisms/haplotypes and anti-tuberculosis drug-induced hepatitis in a Chinese cohort.

PubMed

Tang, Shaowen; Lv, Xiaozhen; Zhang, Yuan; Wu, Shanshan; Yang, Zhirong; Xia, Yinyin; Tu, Dehua; Deng, Peiyuan; Ma, Yu; Chen, Dafang; Zhan, Siyan

2013-01-01

The pathogenic mechanism of anti-tuberculosis (anti-TB) drug-induced hepatitis is associated with drug metabolizing enzymes. No tagging single-nucleotide polymorphisms (tSNPs) of cytochrome P450 2E1(CYP2E1) in the risk of anti-TB drug-induced hepatitis have been reported. The present study was aimed at exploring the role of tSNPs in CYP2E1 gene in a population-based anti-TB treatment cohort. A nested case-control study was designed. Each hepatitis case was 14 matched with controls by age, gender, treatment history, disease severity and drug dosage. The tSNPs were selected by using Haploview 4.2 based on the HapMap database of Han Chinese in Beijing, and detected by using TaqMan allelic discrimination technology. Eighty-nine anti-TB drug-induced hepatitis cases and 356 controls were included in this study. 6 tSNPs (rs2031920, rs2070672, rs915908, rs8192775, rs2515641, rs2515644) were genotyped and minor allele frequencies of these tSNPs were 21.9%, 23.0%, 19.1%, 23.6%, 20.8% and 44.4% in the cases and 20.9%, 22.7%, 18.9%, 23.2%, 18.2% and 43.2% in the controls, respectively. No significant difference was observed in genotypes or allele frequencies of the 6 tSNPs between case group and control group, and neither of haplotypes in block 1 nor in block 2 was significantly associated with the development of hepatitis. Based on the Chinese anti-TB treatment cohort, we did not find a statistically significant association between genetic polymorphisms of CYP2E1 and the risk of anti-TB drug-induced hepatitis. None of the haplotypes showed a significant association with the development of hepatitis in Chinese TB population.

A Nested Case Control Study of Plasma ICAM-1, E-Selectin and TNF Receptor 2 Levels, and Incident Primary Open-Angle Glaucoma

PubMed Central

Kang, Jae H.; Wiggs, Janey L.; Pasquale, Louis R.

2013-01-01

Purpose. To evaluate prediagnostic markers of endothelial dysfunction and inflammatory processes in primary open-angle glaucoma (POAG). Methods. Blood samples were collected from 1989 to 1990 in the Nurses' Health Study (women) and from 1993 to 1995 in the Health Professionals Follow-up Study (men), and medical-record confirmed incident POAG cases were identified (women: 229 cases and 455 controls; men: 116 cases and 228 controls). Controls were matched on cohort, age, race, ethnicity, cancer status, and date of blood collection. Plasma concentrations of ICAM-1, E-selectin, and soluble TNF receptor 2 (sTNF-R2), a marker related to TNF-α, were measured with ELISA assays. Cohort-specific multivariable conditional logistic regression model results were meta-analyzed. Results. We observed no associations with ICAM-1 or E-selectin. For sTNF-R2, the mean (SD) plasma levels (pg/mL) in cases and controls were 2888 (997) and 2993 (913), respectively, in women; and 2622 (664) and 2569 (688), respectively, in men. Pooled multivariable results showed no relation between sTNF-R2 levels and POAG. However, compared with the lowest tertile of sTNF-R2, the highest tertile showed a significant decreased risk of POAG in women (multivariable odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.36–0.93; Ptrend = 0.03) but not in men (Ptrend = 0.21; P for heterogeneity by sex = 0.03). Also, among women, the inverse association with sTNF-R2 was stronger with normal-tension glaucoma (NTG; maximum intraocular pressure <21 mm Hg at diagnosis): highest versus lowest tertile comparison OR = 0.29 (95% CI = 0.12–0.71; Ptrend = 0.007). Conclusions. In women, but not in men, higher sTNF-R2 levels at 6 to 8 years before diagnosis were inversely associated with POAG, but more strongly for NTG. PMID:23412091

Cumulative Exposure to Cell-Free HIV in Breast Milk, Rather Than Feeding Pattern per se, Identifies Postnatally Infected Infants

PubMed Central

Neveu, Dorine; Viljoen, Johannes; Bland, Ruth M.; Nagot, Nicolas; Danaviah, Siva; Coutsoudis, Anna; Rollins, Nigel Campbell; Coovadia, Hoosen M.; Van de Perre, Philippe; Newell, Marie-Louise

2011-01-01

Background. We quantified the relationship between human immunodeficiency virus (HIV) RNA shedding in breast milk, cumulative RNA exposure, and postnatal transmission, relating timing of infection in the infant to estimated total volume of milk exposure. Methods. Nested case-control study of 36 infants of HIV-infected mothers. Case patients were infants who acquired HIV infection through breastfeeding from age 6 through 28 weeks, and control subjects were uninfected infants matched on age at obtainment of a breast milk sample. Mothers and infants received peripartum single-dose nevirapine prophylaxis. Feeding data were collected daily; breast milk samples were collected and infant anthropometry was performed at 6 weeks and monthly thereafter. Volume of milk ingested was estimated using infant weight and feeding pattern. Results. Before HIV acquisition in case patients, feeding pattern (exclusive breastfeeding; median duration, 65 vs 70 days; P = .6) and daily milk intake (mean volume, 638 vs 637 mL; P = .97) did not differ significantly between case patients and control subjects. Case mothers were more likely to shed virus (64% vs 9% always, 22% vs 20.5% intermittently, 14% vs 70.5% never shed; overall, P < .001). Case patients ingested ∼15 times more HIV-1 RNA particles than did control subjects (196.5 vs 13 × 106 copies; P < .001). Allowing for maternal antenatal CD4 cell count and plasma HIV-1 load, child sex and duration of mixed breastfeeding, the association between HIV RNA exposure and infection remained statistically significant (P < .001). Conclusions. Postnatal acquisition of HIV-1 is more strongly associated with cumulative exposure to cell-free particles in breast milk than with feeding mode. Reducing breast milk viral load through antiretroviral therapy to mother or child can further decrease postnatal transmission in exclusively breastfed infants. PMID:21367736

Feline hyperthyroidism reported in primary-care veterinary practices in England: prevalence, associated factors and spatial distribution.

PubMed

Stephens, M J; O'Neill, D G; Church, D B; McGreevy, P D; Thomson, P C; Brodbelt, D C

2014-11-08

Feline hyperthyroidism is a commonly diagnosed endocrinopathy that can have a substantial deleterious impact on the welfare of affected cats. This study aimed to estimate the prevalence, associated factors and geographical distribution for feline hyperthyroidism in England, using primary-care veterinary practice clinical data from the VetCompass Animal Surveillance Project. Prevalence was estimated from the overall cat cohort. Associated factor analysis used an age-matched, nested, case-control design with multivariable logistic regression. There were 2,276 cases of feline hyperthyroidism identified from 95,629 cats attending 84 practices from September 2009 to December 2011. Cases were aged 6-25 years. 3.7 per cent of cases and 9.9 per cent of controls were purebred, 56.4 per cent of cases and 56.5 per cent of controls were female, and 88.1 per cent of cases and 86.0 per cent of controls were neutered. The apparent prevalence was 2.4 per cent (95% CI 2.3 to 2.5 per cent) overall, and 8.7 per cent (95% CI 8.3 to 9.0 per cent) in cats aged 10 years or above. Burmese (OR 0.15, 95% CI 0.07 to 0.32, P<0.0001), Persian (OR 0.17, 95% CI 0.08 to 0.33, P<0.0001), Siamese (OR 0.4, 95% CI 0.21 to 0.75, P=0.004) and purebred cats overall (OR 0.33, 95% CI 0.25 to 0.42, P< 0.0001) had lower odds of feline hyperthyroidism than non-purebred cats. Insured cats had increased odds (OR 1.78, 95% CI 1.56 to 2.03, P< 0.001). There was little evidence of spatial variation. This study highlights feline hyperthyroidism as a high-prevalence disease in England, and reports reduced odds of diagnosis in certain breeds and purebred cats overall. British Veterinary Association.

First trimester serum afamin concentrations are associated with the development of pre-eclampsia and gestational diabetes mellitus in pregnant women.

PubMed

Tramontana, Allessandra; Dieplinger, Benjamin; Stangl, Gerhard; Hafner, Erich; Dieplinger, Hans

2018-01-01

Aim of this study was to assess the prognostic capability of afamin to predict pregnancy complications. First-trimester screening was consecutively performed in 4948 pregnant women, of whom 474 women developed pregnancy complications [gestational hypertension (n=84), pre-eclampsia (n=30), intrauterine growth restriction (n=107), preterm birth (n=44), and gestational diabetes mellitus (n=209)]. To each woman with pregnancy complications an uncomplicated pregnancy was matched for body mass index. Afamin serum concentrations were measured in 948 pregnant women at the first-trimester screening. Median afamin concentrations were significantly higher in women developing pre-eclampsia or gestational diabetes mellitus when compared to women with uncomplicated pregnancies (76mg/L vs. 65mg/L, p=0.001 and 80mg/L vs. 69mg/L, p<0.001). There was no difference in median afamin values between all other pregnancy complications and their matched controls. Increased afamin (i.e. >65mg/L) was a strong and independent predictor for the development of pre-eclampsia (risk ratio, 24.58; 95%CI, 2.82-214.12; p=0.004) as well as gestational diabetes mellitus (risk ratio, 2.07; 95%CI, 1.33-3.22; p=0.001). In this large nested case-control study increased afamin concentrations were a strong and independent predictor for pre-eclampsia and gestational diabetes mellitus, suggesting a potential role of afamin as predictive marker for pregnancy-related metabolic disorders. Copyright © 2017. Published by Elsevier B.V.

Molecular forensics in avian conservation: a DNA-based approach for identifying mammalian predators of ground-nesting birds and eggs.

PubMed

Hopken, Matthew W; Orning, Elizabeth K; Young, Julie K; Piaggio, Antoinette J

2016-01-07

The greater sage-grouse (Centrocercus urophasianus) is a ground-nesting bird from the Northern Rocky Mountains and a species at risk of extinction in in multiple U.S. states and Canada. Herein we report results from a proof of concept that mitochondrial and nuclear DNAs from mammalian predator saliva could be non-invasively collected from depredated greater sage-grouse eggshells and carcasses and used for predator species identification. Molecular forensic approaches have been applied to identify predators from depredated remains as one strategy to better understand predator-prey dynamics and guide management strategies. This can aid conservation efforts by correctly identifying predators most likely to impact threatened and endangered species. DNA isolated from non-invasive samples around nesting sites (e.g. fecal or hair samples) is one method that can increase the success and accuracy of predator species identification when compared to relying on nest remains alone. Predator saliva DNA was collected from depredated eggshells and carcasses using swabs. We sequenced two partial fragments of two mitochondrial genes and obtained microsatellite genotypes using canid specific primers for species and individual identification, respectively. Using this multilocus approach we were able to identify predators, at least down to family, from 11 out of 14 nests (79%) and three out of seven carcasses (47%). Predators detected most frequently were canids (86%), while other taxa included rodents, a striped skunk, and cattle. We attempted to match the genotypes of individual coyotes obtained from eggshells and carcasses with those obtained from fecal samples and coyotes collected in the areas, but no genotype matches were found. Predation is a main cause of nest failure in ground-nesting birds and can impact reproduction and recruitment. To inform predator management for ground-nesting bird conservation, accurate identification of predator species is necessary. Considering predation can have a high impact on recruitment, predation events are very difficult to observe, and predator species are difficult to identify visually from nest remains, molecular approaches that reduce the need to observe or handle animals offer an additional tool to better understand predator-prey dynamics at nesting sites.

Comparison of the diagnostic performance of microscopic examination with nested polymerase chain reaction for optimum malaria diagnosis in Upper Myanmar.

PubMed

Kang, Jung-Mi; Cho, Pyo-Yun; Moe, Mya; Lee, Jinyoung; Jun, Hojong; Lee, Hyeong-Woo; Ahn, Seong Kyu; Kim, Tae Im; Pak, Jhang Ho; Myint, Moe Kyaw; Lin, Khin; Kim, Tong-Soo; Na, Byoung-Kuk

2017-03-16

Accurate diagnosis of Plasmodium infection is crucial for prompt malaria treatment and surveillance. Microscopic examination has been widely applied as the gold standard for malaria diagnosis in most part of malaria endemic areas, but its diagnostic value has been questioned, particularly in submicroscopic malaria. In this study, the diagnostic performance of microscopic examination and nested polymerase chain reaction (PCR) was evaluated to establish optimal malaria diagnosis method in Myanmar. A total of 1125 blood samples collected from residents in the villages and towns located in Naung Cho, Pyin Oo Lwin, Tha Beik Kyin townships and Mandalay of Upper Myanmar were screened by microscopic examination and species-specific nested PCR method. Among the 1125 blood samples, 261 samples were confirmed to be infected with malaria by microscopic examination. Evaluation of the 1125 samples by species-specific nested PCR analysis revealed that the agreement between microscopic examination and nested PCR was 87.3% (261/299). Nested PCR successfully detected 38 Plasmodium falciparum or Plasmodium vivax infections, which were missed in microscopic examination. Microscopic examinations also either misdiagnosed the infected Plasmodium species, or did not detect mixed infections with different Plasmodium species in 31 cases. The nested PCR method is more reliable than conventional microscopic examination for the diagnosis of malaria infections, and this is particularly true in cases of mixed infections and submicroscopic infections. Given the observed higher sensitivity and specificity of nested PCR, the molecular method holds enormous promise in malaria diagnosis and species differentiation, and can be applied as an effective monitoring tool for malaria surveillance, control and elimination in Myanmar.

The association between human papillomavirus infection and lung cancer: a system review and meta-analysis

PubMed Central

Xiong, Wei-Min; Xu, Qiu-Ping; Li, Xu; Xiao, Ren-Dong; Cai, Lin; He, Fei

2017-01-01

To estimate the global attributable fraction of human papillomavirus (HPV) in lung cancer, we provided updated information through a system review and meta-analysis. We did a literature search on PubMed, Ovid and Web of Science to identify case-control studies and cohort studies that detected HPV in lung carcinomas. We included studies that tested 30 or more cases and were published before Feb 28, 2017. We collected information about gender, smoking status, HPV detection methods, HPV types, materials and clinical features. If it was not possible to abstract the required information directly from the papers, we contacted the authors. A meta-analysis was performed to calculate the pooled effect sizes (OR/RR) with 95% confidence intervals (CI) including subgroup analysis and meta-regression to explore sources of heterogeneity, by Stata 13.0 software. 36 case-control studies, contributing data for 6,980 cases of lung cancer and 7,474 controls from 17 countries and one cohort study with 24,162 exposed and 1,026,986 unexposed from China were included. HPV infection was associated with cancer of lung, pooled OR was 3.64 (95% CI: 2.60–5.08), calculated with the random-effects model. Pooled OR for allogeneic case-control studies, self-matched case-control studies and nested case-control studies were 6.71 (95% CI: 4.07–11.07), 2.59 (95% CI: 1.43–4.69) and 0.92 (95% CI: 0.63–1.36), respectively. Pooled OR for HPV 16 and HPV 18 infection, were 3.14 (95% CI: 2.07–4.76) and 2.25 (95% CI: 1.49–3.40), respectively. We also found that HPV infection may be associated with squamous cell carcinoma, adenocarcinoma and small cell carcinoma. There is evidence that HPV infection, especially HPV 16 and HPV 18 infection, significantly increase the risk of lung cancer. Future research needs to focus attention toward whether an HPV vaccine can effectively reduce the incidence of lung cancer. PMID:29221217

Traffic rule violations of private bus drivers and bus crashes in Sri Lanka: a case-control study.

PubMed

Jayatilleke, Achala Upendra; Poudel, Krishna C; Nakahara, Shinji; Dharmaratne, Samath D; Jayatilleke, Achini Chinthika; Jimba, Masamine

2010-06-01

To explore the association between self-reported traffic rule violations of private sector bus drivers and bus crashes in the Kandy district, Sri Lanka. We carried out a case-control study from August to September 2006. Cases were all the private bus drivers registered in the Kandy district and involved in crashes reported to the police between November 2005 and April 2006 (n = 63). We included two control groups: the private bus drivers working on the same routes of the cases (n = 90; matched controls) and the drivers selected randomly from the other routes of the district (n = 111; unmatched controls). We used a self-administered questionnaire to collect data on the self-reported traffic rule violations and analyzed the association between the self-reported traffic rule violations and crashes using logistic regression. The following variables showed significant associations with private bus crashes: illegal overtaking (matched controls, adjusted odds ratio [AOR] = 14.78, unmatched controls, AOR = 1.04), taking passengers outside the bus bays (matched controls, AOR = 3.96, unmatched controls, AOR = 2.29), and overloading (matched controls, AOR = 10.26, unmatched controls, AOR = 1.93). However, we did not observe an association between high-speed driving and bus crashes matched controls, AOR = 1.22, unmatched controls, AOR = 0.81. Traffic rule violations, such as illegal overtaking, overloading, and taking passengers outside the bus bays, are significant risk factors for private bus crashes in Sri Lanka.

An energy-circuit population model for great egrets (Ardea alba) at Lake Okeechobee, Florida, U.S.A

USGS Publications Warehouse

Smith, Jeff P.

1997-01-01

I simulated the annual population cycles of Great Egrets (Ardea alba) at Lake Okeechobee, Florida, to provide a framework for evaluating the local population dynamics of nesting and foraging wading birds. The external forcing functions were solar energy, minimum air temperature, water depth, surface-water drying rate, and season. Solar input controlled the production of prey at moderate to high lake stages, but water area exerted primary control during a two-year drought. Modeling prey production as a linear function of water area resulted in underestimation of prey density during the drought, suggesting that prey organisms maintained high fecundity while concentrated in submerged vegetation at the lakeward fringe of the littoral zone. Simulation confirmed that large influxes of wading birds during the drought were the combined result of a regional refuge response and the availability of concentrated prey. Modeling immigration and emigration as primarily functions of the surface-water drying rate, rather than lake stage, resulted in a closer match of observed and simulated population trends for foraging birds, suggesting that the pattern of surface-water fluctuations was a more important factor than water depth. Simulation indicated an abrupt-threshold response rather than a linear association between foraging efficiency and low temperatures, which reduce activity levels of forage fishes. Great Egret breeder recruitment is primarily a function of prey availability, climate, and hydrologic trends, but simulation confirmed the concurrent involvement of a seasonal or physiological-readiness factor. An attractor function driven by high winter lake stages was necessary to reproduce observed patterns of breeder recruitment, suggesting that Great Egrets initiate nesting based on environmental cues that lead to peak food availability when nestlings are present. Poor correspondence of reproductive effort and nest productivity suggested that the drought compromised the birds' predictive abilities. The need to model breeder recruitment as a function of a maximum rate rather than the size of the local foraging population suggested that birds may nest on the lake even though on-lake foraging conditions are poor. Simulated and observed estimates of egg and hatching production did not match, suggesting that the causes of failure during incubation were complex or more localized than could be accounted for with lakewide hydrologic and climatic data. A forced increase in prey consumption of 12% was necessary to reproduce observed, high levels of nest productivity in 1990, which corresponded to the finding that panhandled fish constituted 10–12% of the biomass fed to Great Egret nestlings that year.

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.

The lack of selection bias in a snowball sampled case-control study on drug abuse.

PubMed

Lopes, C S; Rodrigues, L C; Sichieri, R

1996-12-01

Friend controls in matched case-control studies can be a potential source of bias based on the assumption that friends are more likely to share exposure factors. This study evaluates the role of selection bias in a case-control study that used the snowball sampling method based on friendship for the selection of cases and controls. The cases selected fro the study were drug abusers located in the community. Exposure was defined by the presence of at least one psychiatric diagnosis. Psychiatric and drug abuse/dependence diagnoses were made according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) criteria. Cases and controls were matched on sex, age and friendship. The measurement of selection bias was made through the comparison of the proportion of exposed controls selected by exposed cases (p1) with the proportion of exposed controls selected by unexposed cases (p2). If p1 = p2 then, selection bias should not occur. The observed distribution of the 185 matched pairs having at least one psychiatric disorder showed a p1 value of 0.52 and a p2 value of 0.51, indicating no selection bias in this study. Our findings support the idea that the use of friend controls can produce a valid basis for a case-control study.

Systolic blood pressure variability and lower extremity amputation in a non-elderly population with diabetes.

PubMed

Budiman-Mak, Elly; Epstein, Noam; Brennan, Meghan; Stuck, Rodney; Guihan, Marylou; Huo, Zhiping; Emanuele, Nicholas; Sohn, Min-Woong

2016-04-01

Systolic blood pressure (SBP) variability is emerging as a new risk factor for cardiovascular diseases, diabetic nephropathy, and other atherosclerotic conditions. Our objective is to examine whether it has any prognostic value for lower-extremity amputations. This is a nested case-control study of a cohort of patients with diabetes aged<60 years and treated in the US Department of Veterans Healthcare system in 2003. They were followed over five years for any above-ankle (major) amputations. For each case with a major amputation (event), we randomly selected up to five matched controls based on age, sex, race/ethnicity, and calendar time. SBP variability was computed using three or more blood pressure measures taken during the one-year period before the event. Patients were classified into quartiles according to their SBP variability. The study sample included 1038 cases and 2932 controls. Compared to Quartile 1 (lowest variability), Quartile 2 had 1.4 times (OR=1.44, 95% CI=1.00-2.07) and Quartiles 3 and 4 (highest) had 2.5 times (OR for Quartile 3=2.62, 95% CI=1.85-3.72; OR for Quartile 4=2.50, 95% CI=1.74-3.59) higher risk of major amputation (P for trend<0.001). This gradient relationship held in both normotensive and hypertensive groups as well as for individuals without prior peripheral vascular disease. This is the first study to show a significant graded relationship between SBP variability and risk of major amputation among non-elderly persons with diabetes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Perinatal determinants of germ-cell testicular cancer in relation to histological subtypes

PubMed Central

Richiardi, L; Akre, O; Bellocco, R; Ekbom, A

2002-01-01

We aimed to investigate the role of perinatal determinants on the risk for germ-cell testicular cancer, with respect to the aetiological heterogeneity between seminomas and non-seminomas. A case–control study of 628 case patients with testicular cancer (308 seminomas and 320 non-seminomas) and 2309 individually matched controls was nested within a cohort of boys born from 1920 to 1980 in two Swedish regions (Uppsala-Örebro Health Care Region and Stockholm). Cases were diagnosed from 1958 to 1998 and were identified through the Swedish National Cancer Registry. Perinatal information on cases and controls was collected through charts available at maternity wards. Gestational duration, categorised in three categories (<37, 37–41, >41 weeks), was negatively associated with the risk for testicular cancer (P value for linear trend=0.008). A protective effect of long gestational duration and an increased risk for high birth weight were found for seminomas. Non-seminomas were associated with short gestational duration, particularly among those with low birth order (odds ratio: 3.02, 95% confidence intervals: 1.53–5.97) and high maternal age (odds ratio: 2.33, 95% confidence intervals: 1.19–4.55). No significant differences were found in tests for heterogeneity between the two histological groups. Our data support the hypothesis that intrauterine environment affects the risk for germ-cell testicular cancer. Seminomas and non-seminomas seemed to have similar risk patterns, although they are not entirely congruent. British Journal of Cancer (2002) 87, 545–550. doi:10.1038/sj.bjc.6600470 www.bjcancer.com © 2002 Cancer Research UK PMID:12189554

The Association of Alanine Aminotransferase in Early Pregnancy with Gestational Diabetes.

PubMed

Yarrington, Christina D; Cantonwine, David E; Seely, Ellen W; McElrath, Thomas F; Zera, Chloe A

2016-06-01

Elevated alanine amino transferase, attributed to nonalcoholic fatty liver, is associated with later development of type 2 diabetes mellitus. We sought to determine whether maternal ALT values are associated with subsequent development of gestational diabetes. We performed a nested case-control study utilizing prospectively banked serum samples collected in early gestation. We excluded women with known diabetes, liver disease, or alcohol use. We included 83 cases of gestational diabetes mellitus (GDM) and 247 controls matched for prepregnancy body-mass index (BMI) and compared ALT values. We then performed a conditional logistic regression to model the adjusted odds of GDM in women with ALT ≥19 U/L, stratified by prepregnancy BMI. The median (interquartile range) ALT in cases was 15 (12, 19) IU/L compared to 13 (11, 18) IU/L in controls (P = 0.07). Among women with a prepregnancy BMI <30 kg/m(2), ALT ≥19 U/L was associated with a fourfold increased odds of GDM (adjusted odds ratio [aOR] 4.56 [1.45, 14.27]), while there was no such association among obese women (aOR 0.36 [0.11, 1.20]). Similarly, each unit increase in log-transformed ALT was associated with a threefold increased odds of GDM in nonobese (aOR 3.15 [1.04,9.54]), but not obese (aOR 3.15 [0.30,3.15]) women. The association of high normal ALT and later GDM in nonobese women may reflect the role of hepatic insulin resistance and visceral obesity.

Nested case-control study of autoimmune disease in an asbestos-exposed population.

PubMed

Noonan, Curtis W; Pfau, Jean C; Larson, Theodore C; Spence, Michael R

2006-08-01

To explore the potential association between asbestos exposure and risk of autoimmune disease, we conducted a case-control study among a cohort of 7,307 current and former residents of Libby, Montana, a community with historical occupational and environmental exposure to asbestos-contaminated vermiculite. Cases were defined as those who reported having one of three systemic autoimmune diseases (SAIDs): systemic lupus erythematosus, scleroderma, or rheumatoid arthritis (RA). Controls were randomly selected at a 3:1 ratio from among the remaining 6,813 screening participants using frequency-matched age and sex groupings. The odds ratios (ORs) and 95% confidence intervals (CIs) for SAIDs among those >or=65 years of age who had worked for the vermiculite mining company were 2.14 (95% CI, 0.90-5.10) for all SAIDs and 3.23 (95% CI, 1.31-7.96) for RA. In this age group, exposure to asbestos while in the military was also an independent risk factor, resulting in a tripling in risk. Other measures of occupational exposure to vermiculite indicated 54% and 65% increased risk for SAIDs and RA, respectively. Those who had reported frequent contact with vermiculite through various exposure pathways also demonstrated elevated risk for SAIDs and RA. We found increasing risk estimates for SAIDs with increasing numbers of reported vermiculite exposure pathways (p<0.001). These preliminary findings support the hypothesis that asbestos exposure is associated with autoimmune disease. Refined measurements of asbestos exposure and SAID status among this cohort will help to further clarify the relationship between these variables.

Drug interactions and risk of acute bleeding leading to hospitalisation or death in patients with chronic atrial fibrillation treated with warfarin.

PubMed

Gasse, Christiane; Hollowell, Jennifer; Meier, Christoph R; Haefeli, Walter E

2005-09-01

Although drug interactions with warfarin are an important cause of excessive anticoagulation, their impact on the risk of serious bleeding is unknown. We therefore performed a cohort study and a nested case-control analysis to determine the risk of serious bleeding in 4152 patients (aged 40-84 years) with nonvalvular atrial fibrillation (AF) taking long-term warfarin (> 3 months). The study population was drawn from the UK General Practice Research Database. More than half (58%) of eligible patients used potentially interacting drugs during continuous warfarin treatment. Among 45 identified cases of incident idiopathic bleeds (resulting in hospitalisation within 30 days or death within 7 days) and 143 matched controls, more cases than controls took > or = 1 potentially interacting drug within the preceding 30 days (62.2% vs. 35.7%) and used > 4 drugs (polypharmacy) within the preceding 90 days (80.0% vs. 66.4%). Conditional logistic regression analysis yielded an odds ratio (OR) of 3.4 (95% confidence interval [CI]: 1.4-8.5) for the risk of serious bleeding in patients treated with warfarin and > or = 1 drugs potentially increasing the effect of warfarin vs. warfarin alone adjusted for polypharmacy, diabetes, hypertension, heart failure, and thyroid disease; the adjusted OR for the combined use of warfarin and aspirin vs. warfarin alone was 4.5 (95% CI: 1.1-18.1). We conclude that concurrent use of potentially interacting drugs with warfarin is associated with a 3 to 4.5-fold increased risk of serious bleeding in long-term warfarin users.

Prediagnostic Sex Steroid Hormones in Relation to Male Breast Cancer Risk

PubMed Central

Brinton, Louise A.; Key, Tim J.; Kolonel, Laurence N.; Michels, Karin B.; Sesso, Howard D.; Ursin, Giske; Van Den Eeden, Stephen K.; Wood, Shannon N.; Falk, Roni T.; Parisi, Dominick; Guillemette, Chantal; Caron, Patrick; Turcotte, Véronique; Habel, Laurel A.; Isaacs, Claudine J.; Riboli, Elio; Weiderpass, Elisabete; Cook, Michael B.

2015-01-01

Purpose Although previous studies have implicated a variety of hormone-related risk factors in the etiology of male breast cancers, no previous studies have examined the effects of endogenous hormones. Patients and Methods Within the Male Breast Cancer Pooling Project, an international consortium comprising 21 case-control and cohort investigations, a subset of seven prospective cohort studies were able to contribute prediagnostic serum or plasma samples for hormone quantitation. Using a nested case-control design, multivariable unconditional logistic regression analyses estimated odds ratios and 95% CIs for associations between male breast cancer risk and 11 individual estrogens and androgens, as well as selected ratios of these analytes. Results Data from 101 cases and 217 matched controls were analyzed. After adjustment for age and date of blood draw, race, and body mass index, androgens were found to be largely unrelated to risk, but circulating estradiol levels showed a significant association. Men in the highest quartile had an odds ratio of 2.47 (95% CI, 1.10 to 5.58) compared with those in the lowest quartile (trend P = .06). Assessment of estradiol as a ratio to various individual androgens or sum of androgens showed no further enhancement of risk. These relations were not significantly modified by either age or body mass index, although estradiol was slightly more strongly related to breast cancers occurring among younger (age < 67 years) than older men. Conclusion Our results support the notion of an important role for estradiol in the etiology of male breast cancers, similar to female breast cancers. PMID:25964249

Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease

PubMed Central

Bertoia, Monica L.; Pai, Jennifer K.; Cooke, John P.; Joosten, Michel M.; Mittleman, Murray A.; Rimm, Eric B.; Mukamal, Kenneth J.

2014-01-01

Objective Few studies have examined the roles of homocysteine and related nutrients in the development of peripheral artery disease (PAD). We examined the associations between plasma homocysteine, dietary B vitamins, betaine, choline, and supplemental folic acid use and incidence of PAD. Methods We used two cohort studies of 72,348 women in the Nurses' Health Study (NHS, 1990-2010) and 44,504 men in the Health Professionals Follow-up Study (HPFS, 1986-2010). We measured plasma homocysteine in nested matched case-control studies of clinically recognized PAD within both cohorts, including 143 PAD cases and 424 controls within the NHS (1990-2010) and 143 PAD cases and 428 controls within the HPFS (1994-2008). We examined the association between diet and risk of incident PAD in the cohorts using a food frequency questionnaire and 790 cases of PAD over 3.1 million person-years of follow-up. Results Higher homocysteine levels were positively associated with risk of PAD in men (adjusted IRR 2.17; 95% CI, 1.08-4.38 for tertile 3 vs. 1). There was no evidence of an association in women (adjusted IRR 1.14; 95% CI, 0.61-2.12). Similarly, higher folate intake, including supplements, was inversely associated with risk of PAD in men (adjusted HR 0.90; 95% CI, 0.82-0.98 for each 250 μg increase) but not women (HR 1.01, 95% CI, 0.88-1.15). Intakes of the other B vitamins, betaine, and choline were not consistently associated with risk of PAD in men or women. Conclusion Homocysteine levels were positively associated and dietary folate intake was inversely associated with risk of PAD in men but not in women. PMID:24819748

Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease.

PubMed

Bertoia, Monica L; Pai, Jennifer K; Cooke, John P; Joosten, Michel M; Mittleman, Murray A; Rimm, Eric B; Mukamal, Kenneth J

2014-07-01

Few studies have examined the roles of homocysteine and related nutrients in the development of peripheral artery disease (PAD). We examined the associations between plasma homocysteine, dietary B vitamins, betaine, choline, and supplemental folic acid use and incidence of PAD. We used two cohort studies of 72,348 women in the Nurses' Health Study (NHS, 1990-2010) and 44,504 men in the Health Professionals Follow-up Study (HPFS, 1986-2010). We measured plasma homocysteine in nested matched case-control studies of clinically recognized PAD within both cohorts, including 143 PAD cases and 424 controls within the NHS (1990-2010) and 143 PAD cases and 428 controls within the HPFS (1994-2008). We examined the association between diet and risk of incident PAD in the cohorts using a food frequency questionnaire and 790 cases of PAD over 3.1 million person-years of follow-up. Higher homocysteine levels were positively associated with risk of PAD in men (adjusted IRR 2.17; 95% CI, 1.08-4.38 for tertile 3 vs. 1). There was no evidence of an association in women (adjusted IRR 1.14; 95% CI, 0.61-2.12). Similarly, higher folate intake, including supplements, was inversely associated with risk of PAD in men (adjusted HR 0.90; 95% CI, 0.82-0.98 for each 250 μg increase) but not women (HR 1.01, 95% CI, 0.88-1.15). Intakes of the other B vitamins, betaine, and choline were not consistently associated with risk of PAD in men or women. Homocysteine levels were positively associated and dietary folate intake was inversely associated with risk of PAD in men but not in women. Copyright © 2014. Published by Elsevier Ireland Ltd.

Occupational exposures and lung cancer risk among Minnesota taconite mining workers.

PubMed

Allen, Elizabeth M; Alexander, Bruce H; MacLehose, Richard F; Nelson, Heather H; Ryan, Andrew D; Ramachandran, Gurumurthy; Mandel, Jeffrey H

2015-09-01

To examine the association between employment duration, elongate mineral particle (EMP) exposure, silica exposure and the risk of lung cancer in the taconite mining industry. We conducted a nested case-control study of lung cancer within a cohort of Minnesota taconite iron mining workers employed by any of the mining companies in operation in 1983. Lung cancer cases were identified by vital records and cancer registry data through 2010. Two age-matched controls were selected from risk sets of cohort members alive and lung cancer free at the time of case diagnosis. Calendar time-specific exposure estimates were made for every job and were used to estimate workers' cumulative exposures. ORs and 95% CIs were estimated using conditional logistic regression. We evaluated total lung cancer risk and risk of histological subtype by total work duration and by cumulative EMP, and silica exposure by quartile of the exposure distribution. A total of 1706 cases and 3381 controls were included in the analysis. After adjusting for work in haematite mining, asbestos exposure and sex, the OR for total duration of employment was 0.99 (95% CI 0.96 to 1.01). The ORs for quartile 4 versus 1 of EMP and silica exposure were 0.82 (95% CI 0.57 to 1.19) and 0.97 (95% CI 0.70 to 1.35), respectively. The risk of each histological subtype of lung cancer did not change with increasing exposure. This study suggests that the estimated taconite mining exposures do not increase the risk of developing lung cancer. 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.

Physical activity in middle-aged women and hip fracture risk: the UFO study.

PubMed

Englund, U; Nordström, P; Nilsson, J; Bucht, G; Björnstig, U; Hallmans, G; Svensson, O; Pettersson, U

2011-02-01

In a population-based case-control study, we demonstrate that middle-aged women who were active with walking or in different physical spare time activities were at lower risk of later sustaining a hip fracture compared to more sedentary women. In middle-aged women participating in the Umeå Fracture and Osteoporosis (UFO) study, we investigated whether physical activity is associated with a subsequent decreased risk of sustaining a hip fracture. The UFO study is a nested case-control study investigating associations between bone markers, lifestyle, and osteoporotic fractures. We identified 81 female hip fracture cases that had reported lifestyle data before they sustained their fracture. Each case was compared with two female controls who were identified from the same cohort and matched for age and week of reporting data, yielding a total cohort of 237 subjects. Mean age at baseline was 57.2 ± 5.0 years, and mean age at fracture was 65.4 ± 6.4 years. Conditional logistic regression analysis with adjustments for height, weight, smoking, and menopausal status showed that subjects who were regularly active with walking or had a moderate or high frequency of physical spare time activities (i.e. berry/mushroom picking and snow shovelling) were at reduced risk of sustaining a hip fracture (OR 0.14; 95% CI; 0.05-0.53 for walking and OR 0.19; 95% CI; 0.08-0.46, OR 0.17, 95% CI; 0.05-0.64 for moderate and high frequency of spare time activities, respectively) compared to more sedentary women. An active lifestyle in middle age seems to reduce the risk of future hip fracture. Possible mechanisms may include improved muscle strength, coordination, and balance resulting in a decreased risk of falling and perhaps also direct skeletal benefits.

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

PubMed

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

2018-06-07

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

Use of Proton Pump inhibitors is Associated with Fractures in Young Adults: A Population-Based Study

PubMed Central

Freedberg, Daniel E.; Haynes, Kevin; Denburg, Michelle R.; Zemel, Babette S.; Leonard, Mary B.; Abrams, Julian A.; Yang, Yu-Xiao

2015-01-01

Purpose Proton pump inhibitors (PPIs) are associated with fracture in adults with osteoporosis. Because PPI therapy may interfere with bone accrual and attainment of peak bone mineral density, we studied the association between use of PPIs and fracture in children and young adults. Methods We conducted a population-based, case-control study nested within records from general medical practices from 1994 to 2013. Participants were 4–29 years old with ≥1 year of follow-up who lacked chronic conditions associated with use of long-term acid suppression. Cases of fracture were defined as the first incident fracture at any site. Using incidence density sampling, cases were matched with up to 5 controls by age, sex, medical practice, and start of follow-up. PPI exposure was defined as 180 or more cumulative doses of PPIs. Conditional logistic regression was used to estimate the odds ratio and confidence interval for use of PPIs and fracture. Results We identified 124,799 cases and 605,643 controls. The adjusted odds ratio for the risk of fracture associated with PPI exposure was 1.13 (95% CI 0.92 to 1.39) among children aged < 18 years old and 1.39 (95% CI 1.26 to 1.53) among young adults aged 18–29 years old. In young adults but not children, we observed a dose-response effect with increased total exposure to PPIs (p for trend <.001). Conclusions PPI use was associated with fracture in young adults but overall evidence did not support a PPI-fracture relationship in children. Young adults who use PPIs should be cautioned regarding potentially increased risk for fracture, even if they lack traditional fracture risk factors. PMID:25986385

Occupational Exposures and Lung Cancer Risk among Minnesota Taconite Mining Workers

PubMed Central

Allen, Elizabeth M; Alexander, Bruce H; MacLehose, Richard F; Nelson, Heather H; Ryan, Andrew D; Ramachandran, Gurumurthy; Mandel, Jeffrey H

2015-01-01

Objective To examine the association between employment duration, elongate mineral particle (EMP) exposure, and silica exposure and the risk of lung cancer in the taconite mining industry. Methods We conducted a nested case control study of lung cancer within a cohort of Minnesota taconite iron mining workers employed by any of the mining companies in operation in 1983. Lung cancer cases were identified by vital records and cancer registry data through 2010. Two age-matched controls were selected from risk sets of cohort members alive and lung cancer free at the time of case diagnosis. Calendar time-specific exposure estimates were made for every job and were used to estimate workers’ cumulative exposures. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. We evaluated total lung cancer risk and risk of histological subtype by total work duration and by cumulative EMP and silica exposure by quartile of the exposure distribution. Results A total of 1,706 cases and 3,381 controls were included in the analysis. After adjusting for work in hematite mining, asbestos exposure, and sex, the OR for total duration of employment was 0.99 (95% CI: 0.96–1.01). The ORs for quartile 4 versus 1 of EMP and silica exposure were 0.82 (95% CI: 0.57–1.19) and 0.97 (95% CI: 0.70–1.35) respectively. The risk of each histological subtype of lung cancer did not change with increasing exposure. Conclusions This study suggests that the estimated taconite mining exposures do not increase the risk for the development of lung cancer. PMID:25977445

Risk for Valvular Heart Disease After Treatment for Hodgkin Lymphoma

PubMed Central

Cutter, David J.; Schaapveld, Michael; Darby, Sarah C.; Hauptmann, Michael; van Nimwegen, Frederika A.; Krol, Augustinus D. G.; Janus, Cecile P. M.; van Leeuwen, Flora E.

2015-01-01

Background: Hodgkin lymphoma (HL) survivors are at increased risk for developing valvular heart disease (VHD). We evaluated the determinants of the risk and the radiation dose-response. Methods: A case-control study was nested in a cohort of 1852 five-year HL survivors diagnosed at ages 15 to 41 years and treated between 1965 and 1995. Case patients had VHD of at least moderate severity as their first cardiovascular diagnosis following HL treatment. Control patients were matched to case patients for age, gender, and HL diagnosis date. Treatment and follow-up data were abstracted from medical records. Radiation doses to heart valves were estimated by reconstruction of individual treatments on representative computed tomography datasets. All statistical tests were two-sided. Results: Eighty-nine case patients with VHD were identified (66 severe or life-threatening) and 200 control patients. Aortic (n = 63) and mitral valves (n = 42) were most frequently affected. Risks increased more than linearly with radiation dose. For doses to the affected valve(s) of less than or equal to 30, 31–35, 36–40, and more than 40 Gy, VHD rates increased by factors of 1.4, 3.1, 5.4, and 11.8, respectively (P trend < .001). Approximate 30-year cumulative risks were 3.0%, 6.4%, 9.3%, and 12.4% for the same dose categories. VHD rate increased with splenectomy by a factor of 2.3 (P = .02). Conclusions: Radiation dose to the heart valves can increase the risk for clinically significant VHD, especially at doses above 30 Gy. However, for patients with mediastinal involvement treated today with 20 or 30 Gy, the 30-year risk will be increased by only about 1.4%. These findings may be useful for patients and doctors both before treatment and during follow-up. PMID:25713164

Risk of valvular heart disease after treatment for Hodgkin lymphoma.

PubMed

Cutter, David J; Schaapveld, Michael; Darby, Sarah C; Hauptmann, Michael; van Nimwegen, Frederika A; Krol, Augustinus D G; Janus, Cecile P M; van Leeuwen, Flora E; Aleman, Berthe M P

2015-04-01

Hodgkin lymphoma (HL) survivors are at increased risk of developing valvular heart disease (VHD). We evaluated the determinants of the risk and the radiation dose-response. A case-control study was nested in a cohort of 1852 five-year HL survivors diagnosed at ages 15 to 41 years and treated between 1965 and 1995. Case patients had VHD of at least moderate severity as their first cardiovascular diagnosis following HL treatment. Control patients were matched to case patients for age, gender, and HL diagnosis date. Treatment and follow-up data were abstracted from medical records. Radiation doses to heart valves were estimated by reconstruction of individual treatments on representative computed tomography datasets. All statistical tests were two-sided. Eighty-nine case patients with VHD were identified (66 severe or life-threatening) and 200 control patients. Aortic (n = 63) and mitral valves (n = 42) were most frequently affected. Risks increased more than linearly with radiation dose. For doses to the affected valve(s) of less than or equal to 30, 31-35, 36-40, and more than 40 Gy, VHD rates increased by factors of 1.4, 3.1, 5.4, and 11.8, respectively (P trend < .001). Approximate 30-year cumulative risks were 3.0%, 6.4%, 9.3%, and 12.4% for the same dose categories. VHD rate increased with splenectomy by a factor of 2.3 (P = .02). Radiation dose to the heart valves can increase the risk of clinically significant VHD, especially at doses above 30 Gy. However, for patients with mediastinal involvement treated today with 20 or 30 Gy, the 30-year risk will be increased by only about 1.4%. These findings may be useful for patients and doctors both before treatment and during follow-up. © The Author 2015. Published by Oxford University Press.

Fetal Growth and Childhood Cancer: A Population-Based Study

PubMed Central

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

2013-01-01

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

Association between lifestyle, menstrual/reproductive history, and histological factors and risk of breast cancer in women biopsied for benign breast disease.

PubMed

Arthur, Rhonda; Wang, Yihong; Ye, Kenny; Glass, Andrew G; Ginsberg, Mindy; Loudig, Olivier; Rohan, Thomas

2017-10-01

Women with benign breast disease (BBD) have an increased risk of subsequent breast cancer. However, whether conventional breast cancer risk factors influence risk of breast cancer among women with BBD is unclear. In this study, we investigated the associations of lifestyle, menstrual/reproductive, and histological factors with risk of breast cancer among women biopsied for BBD. We conducted a case-control study, nested within a cohort of 15,395 women biopsied for BBD at Kaiser Permanente Northwest between 1971 and 2006. Cases were women who developed a subsequent invasive breast cancer during follow-up; controls were individually matched to cases on age at BBD diagnosis. A total of 526 case-control pairs were included in the study. We calculated crude and multivariable OR and 95% CI for the associations between lifestyle, menstrual/reproductive, and histological factors and breast cancer risk using conditional logistic regression. Compared to premenopausal women, postmenopausal women had reduced risk of subsequent breast cancer (OR 0.60; 95% CI 0.39-0.94), whereas women who ever used hormone replacement therapy (HRT) had increased risk (OR 3.61; 95% CI 1.68-7.75), as did women whose BBD lesion showed atypical hyperplasia (OR 5.56; 95% CI 2.05-15.06). Smoking, BMI, early menarche, multiparity (≥4), history of oophorectomy, and extent of lobular involution were not associated with risk of breast cancer. This study suggests that use of HRT and having atypical hyperplasia are associated with increased risk of breast cancer among women with BBD, while postmenopausal women with BBD have a reduced risk.

Tactic changes in dusky frillgoby Bathygobius fuscus sneaker males: effects of body size and nest availability.

PubMed

Takegaki, T; Kaneko, T; Matsumoto, Y

2013-02-01

Field and laboratory studies were conducted to examine the effects of nest availability and body size on changes in male mating tactics from sneaking to nest-holding in the dusky frillgoby Bathygobius fuscus. In the field, the body size of nest-holding males decreased from early to mid-breeding season, suggesting the possibility of a change in the tactics of sneaker males to nest-holding. Many sneaker males did not use vacant spawning nests even when size-matched nests were available, but they continued to reproduce as sneakers. Similarly, in aquarium experiments with available vacant nests, some sneaker males became nest-holders irrespective of their body size, but some did not. These results showed that nest availability is not a limiting factor for changes in tactics by sneaker males in this species. Because tactic-unchanged sneaker males were co-housed with larger nest-holding males in the tanks, the body size of nearby nest-holding males may have affected the decision to change tactics for sneaker males. Moreover, smaller individuals among tactic-changed males tended to spend more time until spawning, probably because they had relatively larger costs and smaller benefits of reproduction as nest-holding males compared to larger males. © 2012 The Authors. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

Study design: Evaluating gene–environment interactions in the etiology of breast cancer – the WECARE study

PubMed Central

Bernstein, Jonine L; Langholz, Bryan; Haile, Robert W; Bernstein, Leslie; Thomas, Duncan C; Stovall, Marilyn; Malone, Kathleen E; Lynch, Charles F; Olsen, Jørgen H; Anton-Culver, Hoda; Shore, Roy E; Boice, John D; Berkowitz, Gertrud S; Gatti, Richard A; Teitelbaum, Susan L; Smith, Susan A; Rosenstein, Barry S; Børresen-Dale, Anne-Lise; Concannon, Patrick; Thompson, W Douglas

2004-01-01

Introduction Deficiencies in cellular responses to DNA damage can predispose to cancer. Ionizing radiation can cause cluster damage and double-strand breaks (DSBs) that pose problems for cellular repair processes. Three genes (ATM, BRCA1, and BRCA2) encode products that are essential for the normal cellular response to DSBs, but predispose to breast cancer when mutated. Design To examine the joint roles of radiation exposure and genetic susceptibility in the etiology of breast cancer, we designed a case-control study nested within five population-based cancer registries. We hypothesized that a woman carrying a mutant allele in one of these genes is more susceptible to radiation-induced breast cancer than is a non-carrier. In our study, 700 women with asynchronous bilateral breast cancer were individually matched to 1400 controls with unilateral breast cancer on date and age at diagnosis of the first breast cancer, race, and registry region, and counter-matched on radiation therapy. Each triplet comprised two women who received radiation therapy and one woman who did not. Radiation absorbed dose to the contralateral breast after initial treatment was estimated with a comprehensive dose reconstruction approach that included experimental measurements in anthropomorphic and water phantoms applying patient treatment parameters. Blood samples were collected from all participants for genetic analyses. Conclusions Our study design improves the potential for detecting gene–environment interactions for diseases when both gene mutations and the environmental exposures of interest are rare in the general population. This is particularly applicable to the study of bilateral breast cancer because both radiation dose and genetic susceptibility have important etiologic roles, possibly by interactive mechanisms. By using counter-matching, we optimized the informativeness of the collected dosimetry data by increasing the variability of radiation dose within the case–control sets and enhanced our ability to detect radiation–genotype interactions. PMID:15084244

Risk Factor for Diabetes Mellitus and High Blood Glucose With HMG-CoA Reductase Inhibitors Using a Postmarketing Surveillance Database in Japan.

PubMed

Hashiguchi, Masayuki; Maruyama, Junya; Shimizu, Mikiko; Takahashi, Daichi; Shiga, Tsuyoshi

2018-02-20

To investigate whether 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor (statin) use is associated with an increased risk of diabetes mellitus and hyperglycemia, we performed a nested case-control study using a postmarketing surveillance database in Japan. The database cohort included 26,849 cases of statin use and 5308 cases of other lipid-lowering drug use in patients with hyperlipidemia. Participants received at least 1 type of statin, had a clear medication history of statin use, and had no complications of diabetes mellitus. Cases were defined as onset of diabetes mellitus or hyperglycemia during statin intake. For each case, 20 controls were randomly selected and matched by time point. The factors associated with an increased risk of diabetes mellitus and hyperglycemia during statin intake examined included sex, age, body mass index, statin use duration, complications, concomitant medication, and clinical laboratory tests. Statin-associated diabetes mellitus or hyperglycemia was identified based on abnormal elevation of blood glucose concentrations beyond the reference range. A total of 19,868 patients met the inclusion criteria, of whom 24 were patients in the case group. Two complicating factors, fatty liver (adjusted odds ratio 16.10) and hyperuricemia (adjusted odds ratio 28.96), were extracted for onset of diabetes mellitus or hyperglycemia. Nonalcoholic fatty liver was associated with diabetes mellitus, obesity, and insulin resistance, and hyperuricemia was associated with lifestyle. This study suggested that the onset of diabetes mellitus or hyperglycemia might be increased with statin use in patients with complications of fatty liver and hyperuricemia. © 2018, The American College of Clinical Pharmacology.

Child Maltreatment as a Risk Factor for Opioid Dependence: Comparison of Family Characteristics and Type and Severity of Child Maltreatment with a Matched Control Group

ERIC Educational Resources Information Center

Conroy, Elizabeth; Degenhardt, Louisa; Mattick, Richard P.; Nelson, Elliot C.

2009-01-01

Objective: To examine the prevalence, characteristics and risk factors for child maltreatment among opioid-dependent persons compared to a community sample of similar social disadvantage. Method: The study employed a case-control design. Cases had a history of opioid pharmacotherapy. Controls were frequency matched to cases with regard to age, sex…

Risk of nonfatal acute myocardial infarction associated with non-steroidal antiinflammatory drugs, non-narcotic analgesics and other drugs used in osteoarthritis: a nested case-control study.

PubMed

de Abajo, Francisco J; Gil, Miguel J; García Poza, Patricia; Bryant, Verónica; Oliva, Belén; Timoner, Julia; García-Rodríguez, Luis A

2014-11-01

The purpose of this study is to estimate the risk of nonfatal acute myocardial infarction (AMI) associated with traditional NSAIDs (tNSAIDs), non-narcotic analgesics (paracetamol and metamizole), and symptomatic slow-acting drugs in osteoarthritis (SYSADOAs) overall and in different subgroups of patients. We performed a nested case-control study using a Primary Care Database (Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria), over the study period, 2001-2007. We included patients aged 40-90 years, with nonfatal AMI and randomly selected controls matched for age, sex and calendar year. Exposure to drugs was assessed within a 30-day window before the index date. We did not find an association with nonfatal AMI in patients at low-intermediate background cardiovascular risk (odds ratio = 0.92; 95% confidence interval: 0.76-1.12), whereas there was a moderate significant association among those at high risk (1.28; 1.06-1.54) or when tNSAIDs were used for longer than 365 days (1.43; 1.12-1.82). The greatest risk occurred when these two conditions were combined (1.80; 1.26-2.58). The risk varied across individual tNSAIDs, with ibuprofen (0.95; 0.78-1.16) in the lower and aceclofenac (1.59; 1.15-2.19) in the upper part of the range. Low-dose aspirin did not modify the risk profile showed by any of the individual tNSAIDs examined. Paracetamol (0.84; 0.74-0.95), metamizole (1.06; 0.87-1.29) and SYSADOAs (0.68; 0.47-0.99) were not associated with an increased risk overall or in any subgroup of patients. The risk of nonfatal AMI varied with individual tNSAIDs, duration of treatment and background cardiovascular risk. Paracetamol, metamizole and SYSADOAs did not increase the risk in any of the conditions examined. Copyright © 2014 John Wiley & Sons, Ltd.

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

PubMed

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

2015-03-01

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

Electrocardiographic features of sudden unexpected death in epilepsy.

PubMed

Chyou, Janice Y; Friedman, Daniel; Cerrone, Marina; Slater, William; Guo, Yu; Taupin, Daniel; O'Rourke, Sean; Priori, Silvia G; Devinsky, Orrin

2016-07-01

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of epilepsy-related mortality. We hypothesized that electrocardiography (ECG) features may distinguish SUDEP cases from living subjects with epilepsy. Using a matched case-control design, we compared ECG studies of 12 consecutive cases of SUDEP over 10 years and 22 epilepsy controls matched for age, sex, epilepsy type (focal, generalized, or unknown/mixed type), concomitant antiepileptic, and psychotropic drug classes. Conduction intervals and prevalence of abnormal ventricular conduction diagnosis (QRS ≥110 msec), abnormal ventricular conduction pattern (QRS <110 msec, morphology of incomplete right or left bundle branch block or intraventricular conduction delay), early repolarization, and features of inherited cardiac channelopathies were assessed. Abnormal ventricular conduction diagnosis and pattern distinguished SUDEP cases from matched controls. Abnormal ventricular conduction diagnosis was present in two cases and no controls. Abnormal ventricular conduction pattern was more common in cases than controls (58% vs. 18%, p = 0.04). Early repolarization was similarly prevalent in cases and controls, but the overall prevalence exceeded that of published community-based cohorts. Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.

Preclinical serum 25-hydroxyvitamin D levels and risk of type 1 diabetes in a cohort of US military personnel.

PubMed

Munger, Kassandra L; Levin, Lynn I; Massa, Jennifer; Horst, Ronald; Orban, Tihamer; Ascherio, Alberto

2013-03-01

To determine whether serum levels of 25-hydroxyvitamin D (25(OH)D) in young adults are associated with risk of type 1 diabetes mellitus (T1D), we conducted a prospective, nested case-control study among US active-duty military personnel with serum in the US Department of Defense Serum Repository, identifying 310 T1D cases diagnosed between 1997 and 2009 with at least 2 serum samples collected before disease onset and 613 controls matched to cases on age, sex, race/ethnicity, branch of military service, and dates of serum collection. Conditional logistic regression was used to estimate rate ratios and 95% confidence intervals. Among non-Hispanic whites, those with average 25(OH)D levels of ≥ 100 nmol/L had a 44% lower risk of developing T1D than those with average 25(OH)D levels < 75 nmol/L (rate ratio = 0.56, 95% confidence interval: 0.35, 0.90, P for trend = 0.03) over an average follow-up of 5.4 years. In quintile analyses, T1D risk was highest among individuals whose 25(OH)D levels were in the lowest 20% of those measured. There was no association between 25(OH)D levels and risk of T1D among non-Hispanic blacks or Hispanics. Low 25(OH)D levels may predispose healthy, young, non-Hispanic white adults to the development of T1D.

Preclinical Serum 25-Hydroxyvitamin D Levels and Risk of Type 1 Diabetes in a Cohort of US Military Personnel

PubMed Central

Munger, Kassandra L.; Levin, Lynn I.; Massa, Jennifer; Horst, Ronald; Orban, Tihamer; Ascherio, Alberto

2013-01-01

To determine whether serum levels of 25-hydroxyvitamin D (25(OH)D) in young adults are associated with risk of type 1 diabetes mellitus (T1D), we conducted a prospective, nested case-control study among US active-duty military personnel with serum in the US Department of Defense Serum Repository, identifying 310 T1D cases diagnosed between 1997 and 2009 with at least 2 serum samples collected before disease onset and 613 controls matched to cases on age, sex, race/ethnicity, branch of military service, and dates of serum collection. Conditional logistic regression was used to estimate rate ratios and 95% confidence intervals. Among non-Hispanic whites, those with average 25(OH)D levels of ≥100 nmol/L had a 44% lower risk of developing T1D than those with average 25(OH)D levels <75 nmol/L (rate ratio = 0.56, 95% confidence interval: 0.35, 0.90, P for trend = 0.03) over an average follow-up of 5.4 years. In quintile analyses, T1D risk was highest among individuals whose 25(OH)D levels were in the lowest 20% of those measured. There was no association between 25(OH)D levels and risk of T1D among non-Hispanic blacks or Hispanics. Low 25(OH)D levels may predispose healthy, young, non-Hispanic white adults to the development of T1D. PMID:23380046

Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

PubMed

Stolzenberg-Solomon, Rachael Z; Jacobs, Eric J; Arslan, Alan A; Qi, Dai; Patel, Alpa V; Helzlsouer, Kathy J; Weinstein, Stephanie J; McCullough, Marjorie L; Purdue, Mark P; Shu, Xiao-Ou; Snyder, Kirk; Virtamo, Jarmo; Wilkins, Lynn R; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Albanes, Demetrius; Cai, Qiuyin; Harvey, Chinonye; Hayes, Richard; Clipp, Sandra; Horst, Ronald L; Irish, Lonn; Koenig, Karen; Le Marchand, Loic; Kolonel, Laurence N

2010-07-01

Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974-2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50-<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (> or =100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered.

Impaired functional vitamin B6 status is associated with increased risk of lung cancer.

PubMed

Theofylaktopoulou, Despoina; Midttun, Øivind; Ueland, Per M; Meyer, Klaus; Fanidi, Anouar; Zheng, Wei; Shu, Xiao-Ou; Xiang, Yong-Bing; Prentice, Ross; Pettinger, Mary; Thomson, Cynthia A; Giles, Graham G; Hodge, Allison; Cai, Qiuyin; Blot, William J; Wu, Jie; Johansson, Mikael; Hultdin, Johan; Grankvist, Kjell; Stevens, Victoria L; McCullough, Marjorie M; Weinstein, Stephanie J; Albanes, Demetrius; Ziegler, Regina; Freedman, Neal D; Langhammer, Arnulf; Hveem, Kristian; Naess, Marit; Sesso, Howard D; Gaziano, J Michael; Buring, Julie E; Lee, I-Min; Severi, Gianluca; Zhang, Xuehong; Stampfer, Meir J; Han, Jiali; Smith-Warner, Stephanie A; Zeleniuch-Jacquotte, Anne; Le Marchand, Loic; Yuan, Jian-Min; Wang, Renwei; Butler, Lesley M; Koh, Woon-Puay; Gao, Yu-Tang; Rothman, Nathaniel; Ericson, Ulrika; Sonestedt, Emily; Visvanathan, Kala; Jones, Miranda R; Relton, Caroline; Brennan, Paul; Johansson, Mattias; Ulvik, Arve

2018-06-15

Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR 4th vs. 1st ) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status. © 2017 UICC.

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

Farm- and flock-level risk factors associated with Highly Pathogenic Avian Influenza outbreaks on small holder duck and chicken farms in the Mekong Delta of Viet Nam.

PubMed

Henning, Kate A; Henning, Joerg; Morton, John; Long, Ngo Thanh; Ha, Nguyen Truc; Meers, Joanne

2009-10-01

After 11 consecutive months of control, the Mekong Delta in Viet Nam experienced a wave of Highly Pathogenic Avian Influenza (HPAI) H5N1 outbreaks on small holder poultry farms from December 2006 to January 2007. We conducted a retrospective matched case-control study to investigate farm- and flock-level risk factors for outbreak occurrence during this period. Twenty-two case farms were selected from those where clinical signs consistent with HPAI H5N1 had been present and HPAI H5N1 had been confirmed with a positive real-time PCR test from samples obtained from affected birds. For every case farm enrolled, two control farms were selected matched on time of outbreak occurrence, farm location and species. Veterinarians conducted interviews with farmers, to collect information on household demographics, farm characteristics, husbandry practices, trading practices, poultry health, vaccination and biosecurity. Exact stratified logistic regression models were used to assess putative risk factors associated with a flock having or not having a HPAI outbreak. Nested analyses were also performed, restricted to subsets of farms using scavenging, confinement or supplementary feeding practices. Risk of an outbreak of HPAI H5N1 was increased in flocks that had received no vaccination (odds ratio (OR)=20.2; 95% confidence interval (CI): 1.0, +infinity) or only one vaccination (OR=85.2; 95% CI: 6.5, +infinity) of flocks compared to two vaccinations, and in flocks on farms that had family and friends visiting (OR=8.2; 95% CI: 1.0, +infinity) and geese present (OR=11.5; 95% CI: 1.1, +infinity). The subset analysis using only flocks that scavenged showed that sharing of scavenging areas with flocks from other farms was associated with increased risk of an outbreak (OR=10.9; 95% CI: 1.4, 492.9). We conclude that none or only one vaccination, visitors to farms, the presence of geese on farms and sharing of scavenging areas with ducks from other farms increase the risk of HPAI H5N1 outbreaks in poultry flocks in Viet Nam.

Higher protein intake is associated with increased risk for incident end-stage renal disease among blacks with diabetes in the Southern Community Cohort Study.

PubMed

Malhotra, R; Cavanaugh, K L; Blot, W J; Ikizler, T A; Lipworth, L; Kabagambe, E K

2016-12-01

Diabetes, a risk factor for end-stage renal disease (ESRD), is associated with impaired protein metabolism. We investigated whether protein intake is associated with ESRD and whether the risk is higher among blacks with diabetes. We conducted a nested case-control study of ESRD within the Southern Community Cohort Study, a prospective study of low-income blacks and whites in the southeastern US (2002-2009). Through 2012, 1057 incident ESRD cases were identified by linkage with the United States Renal Data System and matched to 3198 controls by age, sex, and race. Dietary intakes were assessed from a validated food frequency questionnaire at baseline. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from logistic regression models that included matching variables, BMI, education, income, hypertension, total energy intake, and percent energy from saturated and polyunsaturated fatty acids. Mean (±SD) daily energy intake from protein was higher among ESRD cases than controls (15.7 ± 3.3 vs. 15.1 ± 3.1%, P < 0.0001). For a 1% increase in percent energy intake from protein, the adjusted ORs (95% CIs) for ESRD were 1.06 (1.02-1.10) for blacks with diabetes, 1.02 (0.98-1.06) for blacks without diabetes, 0.99 (0.90-1.09) for whites with diabetes and 0.94 (0.84-1.06) for whites without diabetes. Protein intake in g/kg/day was also associated with ESRD (4th vs. 1st quartile OR = 1.76; 95% CI: 1.17-2.65). Our results raise the possibility that among blacks with diabetes, increased dietary protein is associated with increased incidence of ESRD. Studies on how protein intake and metabolism affect ESRD are needed. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Maternal urinary bisphenol A levels and infant low birth weight: A nested case-control study of the Health Baby Cohort in China.

PubMed

Huo, Wenqian; Xia, Wei; Wan, Yanjian; Zhang, Bin; Zhou, Aifen; Zhang, Yiming; Huang, Kai; Zhu, Yingshuang; Wu, Chuansha; Peng, Yang; Jiang, Minmin; Hu, Jie; Chang, Huailong; Xu, Bing; Li, Yuanyuan; Xu, Shunqing

2015-12-01

Exposure to bisphenol A (BPA), a known endocrine disruptor, has been demonstrated to affect fetal development in animal studies, but findings in human studies have been inconsistent. We investigated whether maternal exposure to BPA during pregnancy is associated with an increased risk of infant low birth weight (LBW). A total 452 mother-infant pairs (113 LBW cases and 339 matched controls) were selected from the participants enrolled in the prospective Health Baby Cohort (HBC) in Wuhan city, China, during 2012-2014. BPA concentrations were measured in maternal urine samples collected at delivery, and the information of birth outcomes was retrieved from the medical records. A conditional logistic regression was used to evaluate the relationship between urinary BPA levels and LBW. Mothers with LBW infants had significantly higher urinary BPA levels (median: 4.70μg/L) than the control mothers (median: 2.25μg/L) (p<0.05). Increased risk of LBW was associated with higher maternal urinary levels of BPA [adjusted odds ratio (OR)=3.13 for the medium tertile, 95% confidence interval (CI): 1.21, 8.08; adjusted OR=2.49 for the highest tertile, 95% CI: 0.98, 6.36]. The association was more pronounced among female infants than among male infants, with a statistical evidence of heterogeneity in risk (p=0.03). Prenatal exposure to higher levels of BPA may potentially increase the risk of delivering LBW infants, especially for female infants. This is the first case-control study to examine the association in China. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cancer-associated autoantibodies to MUC1 and MUC4--a blinded case–control study of colorectal cancer in UK collaborative trial of ovarian cancer screening.

PubMed

Pedersen, Johannes W; Gentry-Maharaj, Aleksandra; Nøstdal, Alexander; Fourkala, Evangelia-Ourania; Dawnay, Anne; Burnell, Matthew; Zaikin, Alexey; Burchell, Joy; Papadimitriou, Joyce Taylor; Clausen, Henrik; Jacobs, Ian; Menon, Usha; Wandall, Hans H

2014-05-01

Recent reports suggest that autoantibodies directed to aberrantly glycosylated mucins, in particular MUC1 and MUC4, are found in patients with colorectal cancer. There is, however, limited information on the autoantibody levels before clinical diagnosis, and their utility in cancer screening in the general population. In our study, we have generated O-glycosylated synthetic MUC1 and MUC4 peptides in vitro, to mimic cancer-associated glycoforms, and displayed these on microarrays. The assay's performance was tested through an initial screening of serum samples taken from patients at the time of colorectal cancer diagnosis and healthy controls. Subsequently, the selected biomarkers were evaluated in a blinded nested case–control study using stored serum samples from among the 50,640 women randomized to the multimodal arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), where women gave annual blood samples for several years. Cases were 97 postmenopausal women who developed colorectal cancer after recruitment and were age-matched to 97 women without any history of cancer. MUC1-STn and MUC1-Core3 IgG autoantibodies identified cases with 8.2 and 13.4% sensitivity, respectively, at 95% specificity. IgA to MUC4 glycoforms were unable to discriminate between cases and controls in the UKCTOCS sera. Additional analysis was undertaken by combining the data of MUC1-STn and MUC1-Core3 with previously generated data on autoantibodies to p53 peptides, which increased the sensitivity to 32.0% at 95% specificity. These findings suggest that a combination of antibody signatures may have a role as part of a biomarker panel for the early detection of colorectal cancer.

Smoking, obesity and risk of sarcoidosis: A population-based nested case-control study.

PubMed

Ungprasert, Patompong; Crowson, Cynthia S; Matteson, Eric L

2016-11-01

Smoking and obesity might alter the risk of sarcoidosis. However, the data remained inconclusive. A cohort of Olmsted County, Minnesota residents diagnosed with sarcoidosis between January 1, 1976 and December 31, 2013 was identified based on individual medical record review. For each sarcoidosis subject, one sex and aged-matched control without sarcoidosis was randomly selected from the same underlying population. Medical records of cases and controls were reviewed for smoking status at index date and body mass index (BMI) within 1 year before to 3 months after index date. 345 incident cases of sarcoidosis and 345 controls were identified. The odds ratio of sarcoidosis comparing current smokers with never smokers adjusted for age and sex was 0.34 (95% confidence interval (CI), 0.23-0.50). The odds ratio of sarcoidosis comparing current smokers with never smokers and former smokers adjusted for age and sex was 0.38 (95% CI, 0.26-0.56). The odds ratio of sarcoidosis comparing overweight subjects (BMI ≥ 25 kg/m 2 but < 30 kg/m 2 ) with subjects with normal/low BMI was 1.12 (95% CI, 0.72-1.75). The odds ratio of sarcoidosis comparing obese subjects (BMI ≥ 30 kg/m 2 ) with subjects with normal/low BMI was 2.54 (95% CI, 1.58-4.06). The odds ratio of sarcoidosis comparing obese subjects with non-obese subjects was 2.38 (95% CI, 1.60-3.56). In this population, current smokers have a lower risk of developing sarcoidosis while subjects with obesity have a higher risk of developing sarcoidosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

The risk of childhood autism among second-generation migrants in Finland: a case-control study.

PubMed

Lehti, Venla; Hinkka-Yli-Salomäki, Susanna; Cheslack-Postava, Keely; Gissler, Mika; Brown, Alan S; Sourander, Andre

2013-10-19

Studying second-generation immigrants can help in identifying genetic or environmental risk factors for childhood autism. Most previous studies have focused on maternal region of birth and showed inconsistent results. No previous study has been conducted in Finland. The study was a nested case-control study based on a national birth cohort. Children born in 1987-2005 and diagnosed with childhood autism by the year 2007 were identified from the Finnish Hospital Discharge Register. Controls were selected from the Finnish Medical Birth Register. Information on maternal and paternal country of birth and mother tongue was collected from the Finnish Central Population Register. There were 1132 cases and 4515 matched controls. The statistical test used was conditional logistic regression analysis. Compared with children with two Finnish parents, the risk of childhood autism was increased for those whose parents are both immigrants (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI] 1.2-2.7) and for those with only an immigrant mother (aOR 1.8, 95% CI 1.2-2.7), but not for those with only an immigrant father. The risk was increased for those with a mother born in the former Soviet Union or Yugoslavia and for those with a mother or a father born in Asia. Specific parental countries of birth associated with an increased risk were the former Soviet Union, the former Yugoslavia and Vietnam. In Finland, children who are born to immigrant mothers with or without an immigrant partner, have an increased risk of childhood autism. The risk varies with immigrant parents' region of birth. The findings may help in identifying possible risk factors, which can be examined in future studies.

Attention Deficit/Hyperactivity Disorder and Childhood Autism in Association with Prenatal Exposure to Perfluoroalkyl Substances: A Nested Case–Control Study in the Danish National Birth Cohort

PubMed Central

Liew, Zeyan; Ritz, Beate; von Ehrenstein, Ondine S.; Bech, Bodil Hammer; Nohr, Ellen Aagaard; Fei, Chunyuan; Bossi, Rossana; Henriksen, Tine Brink; Bonefeld-Jørgensen, Eva Cecilie

2014-01-01

Background: Perfluoroalkyl substances (PFASs) are persistent pollutants found to be endocrine disruptive and neurotoxic in animals. Positive correlations between PFASs and neurobehavioral problems in children were reported in cross-sectional data, but findings from prospective studies are limited. Objectives: We investigated whether prenatal exposure to PFASs is associated with attention deficit/hyperactivity disorder (ADHD) or childhood autism in children. Methods: Among 83,389 mother–child pairs enrolled in the Danish National Birth Cohort during 1996–2002, we identified 890 ADHD cases and 301 childhood autism cases from the Danish National Hospital Registry and the Danish Psychiatric Central Registry. From this cohort, we randomly selected 220 cases each of ADHD and autism, and we also randomly selected 550 controls frequency matched by child’s sex. Sixteen PFASs were measured in maternal plasma collected in early or mid-pregnancy. We calculated risk ratios (RRs) using generalized linear models, taking into account sampling weights. Results: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were detected in all samples; four other PFASs were quantified in ≥ 90% of the samples. We did not find consistent evidence of associations between mother’s PFAS plasma levels and ADHD [per natural log nanograms per milliliter increase: PFOS RR = 0.87 (95% CI: 0.74, 1.02); PFOA RR = 0.98 (95% CI: 0.82, 1.16)] or autism [per natural log nanograms per milliliter increase: PFOS RR = 0.92 (95% CI: 0.69, 1.22); PFOA RR = 0.98 (95% CI: 0.73, 1.31)]. We found positive as well as negative associations between higher PFAS quartiles and ADHD in models that simultaneously adjusted for all PFASs, but these estimates were imprecise. Conclusions: In this study we found no consistent evidence to suggest that prenatal PFAS exposure increases the risk of ADHD or childhood autism in children. Citation: Liew Z, Ritz B, von Ehrenstein OS, Bech BH, Nohr EA, Fei CY, Bossi R, Henriksen TB, Bonefeld-Jørgensen EC, Olsen J. 2015. Attention deficit/hyperactivity disorder and childhood autism in association with prenatal exposure to perfluoroalkyl substances: a nested case–control study in the Danish National Birth Cohort. Environ Health Perspect 123:367–373; http://dx.doi.org/10.1289/ehp.1408412 PMID:25616253

Escape Distance in Ground-Nesting Birds Differs with Individual Level of Camouflage.

PubMed

Wilson-Aggarwal, Jared K; Troscianko, Jolyon T; Stevens, Martin; Spottiswoode, Claire N

2016-08-01

Camouflage is one of the most widespread antipredator strategies in the animal kingdom, yet no animal can match its background perfectly in a complex environment. Therefore, selection should favor individuals that use information on how effective their camouflage is in their immediate habitat when responding to an approaching threat. In a field study of African ground-nesting birds (plovers, coursers, and nightjars), we tested the hypothesis that individuals adaptively modulate their escape behavior in relation to their degree of background matching. We used digital imaging and models of predator vision to quantify differences in color, luminance, and pattern between eggs and their background, as well as the plumage of incubating adult nightjars. We found that plovers and coursers showed greater escape distances when their eggs were a poorer pattern match to the background. Nightjars sit on their eggs until a potential threat is nearby, and, correspondingly, they showed greater escape distances when the pattern and color match of the incubating adult's plumage-rather than its eggs-was a poorer match to the background. Finally, escape distances were shorter in the middle of the day, suggesting that escape behavior is mediated by both camouflage and thermoregulation.

Perinatal factors and the risk of bipolar disorder in Finland.

PubMed

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

2014-02-01

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

Predictive factors of flares in systemic lupus erythematosus patients: data from a multiethnic Latin American cohort.

PubMed

Ugarte-Gil, M F; Wojdyla, D; Pastor-Asurza, C A; Gamboa-Cárdenas, R V; Acevedo-Vásquez, E M; Catoggio, L J; García, M A; Bonfá, E; Sato, E I; Massardo, L; Pascual-Ramos, V; Barile, L A; Reyes-Llerena, G; Iglesias-Gamarra, A; Molina-Restrepo, J F; Chacón-Díaz, R; Alarcón, G S; Pons-Estel, B A

2018-04-01

Purpose The purpose of this paper is to determine the factors predictive of flares in systemic lupus erythematosus (SLE) patients. Methods A case-control study nested within the Grupo Latino Americano De Estudio de Lupus (GLADEL) cohort was conducted. Flare was defined as an increase ≥4 points in the SLEDAI. Cases were defined as patients with at least one flare. Controls were selected by matching cases by length of follow-up. Demographic and clinical manifestations were systematically recorded by a common protocol. Glucocorticoid use was recorded as average daily dose of prednisone and antimalarial use as percentage of time on antimalarial and categorized as never (0%), rarely (>0-25%), occasionally (>25%-50%), commonly (˃50%-75%) and frequently (˃75%). Immunosuppressive drugs were recorded as used or not used. The association between demographic, clinical manifestations, therapy and flares was examined using univariable and multivariable conditional logistic regression models. Results A total of 465 cases and controls were included. Mean age at diagnosis among cases and controls was 27.5 vs 29.9 years, p = 0.003; gender and ethnic distributions were comparable among both groups and so was the baseline SLEDAI. Independent factors protective of flares identified by multivariable analysis were older age at diagnosis (OR = 0.929 per every five years, 95% CI 0.869-0.975; p = 0.004) and antimalarial use (frequently vs never, OR = 0.722, 95% CI 0.522-0.998; p = 0.049) whereas azathioprine use (OR = 1.820, 95% CI 1.309-2.531; p < 0.001) and SLEDAI post-baseline were predictive of them (OR = 1.034, 95% CI 1.005-1.064; p = 0.022). Conclusions In this large, longitudinal Latin American cohort, older age at diagnosis and more frequent antimalarial use were protective whereas azathioprine use and higher disease activity were predictive of flares.

Association of Parkinsonism or Parkinson Disease with Polypharmacy in the Year Preceding Diagnosis: A Nested Case-Control Study in South Korea.

PubMed

Park, Hae-Young; Park, Ji-Won; Sohn, Hyun Soon; Kwon, Jin-Won

2017-11-01

Published studies on the association between polypharmacy and parkinsonism or Parkinson disease are very limited. The objective of this study was to investigate whether polypharmacy is associated with parkinsonism or Parkinson disease in elderly patients. From a South Korean national health insurance sample cohort database for 2002-2013, we matched parkinsonism cases (defined by diagnosis codes for parkinsonism/Parkinson disease) and Parkinson disease cases (patients who had records for both Parkinson disease diagnosis and anti-Parkinson disease drug prescriptions) with controls. Logistic regression analysis evaluated the associations of parkinsonism/Parkinson disease with polypharmacy (i.e., five or more prescribed daily drugs) during the year preceding parkinsonism/Parkinson disease diagnosis, medications potentially associated with parkinsonism, and comorbidity status (using the Charlson Comorbidity Index score and hospitalization records). The study population included 6209 cases and 24,836 controls for parkinsonism and 1331 cases and 5324 controls for Parkinson disease. In univariate logistic regression, odds ratios for parkinsonism/Parkinson disease increased significantly with increased polypharmacy, medications potentially associated with parkinsonism, Charlson Comorbidity Index score, or prior hospitalizations. In multiple logistic regression, odds ratios for parkinsonism/Parkinson disease (adjusted for medications potentially associated with parkinsonism and comorbidities) also increased with increased polypharmacy. Odds ratios (95% confidence interval) for Parkinson disease were higher than those for parkinsonism with stronger statistical significance: 1.41 (1.28-1.55) and 2.17 (1.84-2.57) for parkinsonism and 2.87 (2.30-3.58) and 4.75 (3.39-6.66) for Parkinson disease for between five and ten prescribed daily drugs and ten or more drugs, respectively. Polypharmacy in the year preceding diagnosis may be associated with an increased risk for parkinsonism/Parkinson disease. Medications potentially associated with parkinsonism were assumed to increase the risk for parkinsonism/Parkinson disease, but more studies are required to confirm this relationship.

Excess atherosclerosis in systemic lupus erythematosus,—A matter of renal involvement: Case control study of 281 SLE patients and 281 individually matched population controls

PubMed Central

Gustafsson, Johanna T.; Herlitz Lindberg, Marie; Gunnarsson, Iva; Pettersson, Susanne; Elvin, Kerstin; Öhrvik, John; Larsson, Anders; Jensen-Urstad, Kerstin

2017-01-01

Background Systemic lupus erythematosus (SLE), is a heterogeneous disease which predominantly affects young females (90%). SLE is associated with a shorter life expectancy than in the general population. Standardized mortality ratios (SMR) of 2.4 have been reported, which is comparable to diabetes. In modern societies cardiovascular disease (CVD) is the major cause of premature mortality. Accelerated atherosclerosis is generally assumed to be the underlying cause for SLE related CVD. However, previous studies diverge regarding whether atherosclerosis is more common in SLE than in controls. With this in mind and based on own clinical experience we hypothesized that accelerated atherosclerosis is not a general feature of SLE, but prevails in SLE subgroups. Methods 281 SLE patients and 281 individually age and sex matched population controls, were investigated clinically. Fasting blood samples and risk factor data were collected. All participants were subject to B-mode ultrasonography of the carotid arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were recorded. Two SLE subgroups previously described to be at high CVD risk; 1) patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL), and one subgroup reported to be at comparatively lower CVD risk; patients positive for Sjögren´s syndrome antigens A/B (SSA/SSB) antibodies were analyzed separately in comparison with their respective matched controls. Results Median age was 49 (IQR 36–59) years, 93% were females. Manifest CVD; ischemic heart, cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%, p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age adjustment plaques, but not mIMT, remained associated with previous CVD events. Therefore we focused further analyses on plaques, a more robust measure of atherosclerosis. Patients with nephritis (40%), but neither aPL (25%) nor SSA/SSB (40%) positive patients, had more plaques than their respective controls (23% vs. 11%, p = 0.008). Notably, patients with nephritis were younger than other SLE patients (45 vs.49 years, p = 0.02). To overcome the confounding effect of age we performed an age-matched nested case-control analysis, which demonstrated that patients with nephritis had twice as often plaques (23%) as both non-nephritis patients (11%, p = 0.038) and controls (12%, p = 0.035). Conclusions In SLE excess carotid plaques are essentially confined to the SLE subgroup with nephritis. This subgroup had plaques twice as often as age-matched non-nephritis SLE patients and population controls. Non-nephritis SLE patients, including the aPL positive subgroup, which has a high CVD risk, had similar prevalence of plaques as controls. To prevent later CVD events, this novel observation calls for risk factor screening and initiation of anti-atherosclerotic treatment selectively in SLE nephritis patients. Preferably at nephritis onset, which is often at a young age. In a general perspective this study demonstrates the importance to perform careful clinical subgroup analyses when investigating heterogeneous, hitherto not clearly defined, conditions like SLE. PMID:28414714

Differentiation of Mycobacterium tuberculosis complex from non-tubercular mycobacteria by nested multiplex PCR targeting IS6110, MTP40 and 32kD alpha antigen encoding gene fragments.

PubMed

Sinha, Pallavi; Gupta, Anamika; Prakash, Pradyot; Anupurba, Shampa; Tripathi, Rajneesh; Srivastava, G N

2016-03-12

Control of the global burden of tuberculosis is obstructed due to lack of simple, rapid and cost effective diagnostic techniques that can be used in resource poor-settings. To facilitate the early diagnosis of TB directly from clinical specimens, we have standardized and validated the use of nested multiplex PCR, targeting gene fragments IS6110, MTP40 and 32kD α-antigen encoding genes specific for Mycobacterium tuberculosis complex and non-tubercular mycobacteria (NTM), in comparison to smear microscopy, solid culture and single step multiplex PCR. The results were evaluated in comparison to a composite reference standard (CRS) comprising of microbiological results (smear and culture), clinical, radiological and cytopathological findings, clinical treatment and response to anti-tubercular therapy. The nested multiplex PCR (nMPCR) assay was evaluated to test its utility in 600 (535 pulmonary and 65 extra-pulmonary specimens) clinically suspected TB cases. All specimens were processed for smear, culture, single step multiplex PCR and nested multiplex PCR testing. Out of 535 screened pulmonary and 65 extra-pulmonary specimens, 329 (61.5%) and 19 (29.2%) cases were culture positive for M. tuberculosis. Based on CRS, 450 patients had "clinical TB" (definitive-TB, probable-TB and possible-TB). Remaining 150 were confirmed "non-TB" cases. For culture, the sensitivity was low, 79.3% for pulmonary and 54.3% for extra-pulmonary cases. The sensitivity and specificity results for nMPCR test were evaluated taken composite reference standard as a gold standard. The sensitivity of the nMPCR assay was 97.1% for pulmonary and 91.4% for extra-pulmonary TB cases with specificity of 100% and 93.3% respectively. Nested multiplex PCR using three gene primers is a rapid, reliable and highly sensitive and specific diagnostic technique for the detection and differentiation of M. tuberculosis complex from NTM genome and will be useful in diagnosing paucibacillary samples. Nested multiplex PCR assay was found to be better than single step multiplex PCR for assessing the diagnosis of TB.

How do gamblers end gambling: longitudinal analysis of Internet gambling behaviors prior to account closure due to gambling related problems.

PubMed

Xuan, Ziming; Shaffer, Howard

2009-06-01

To examine behavioral patterns of actual Internet gamblers who experienced gambling-related problems and voluntarily closed their accounts. A nested case-control design was used to compare gamblers who closed their accounts because of gambling problems to those who maintained open accounts. Actual play patterns of in vivo Internet gamblers who subscribed to an Internet gambling site. 226 gamblers who closed accounts due to gambling problems were selected from a cohort of 47,603 Internet gamblers who subscribed to an Internet gambling site during February 2005; 226 matched-case controls were selected from the group of gamblers who did not close their accounts. Daily aggregates of behavioral data were collected during an 18-month study period. Main outcomes of interest were daily aggregates of stake, odds, and net loss, which were standardized by the daily aggregate number of bets. We also examined the number of bets to measure trajectory of gambling frequency. Account closers due to gambling problems experienced increasing monetary loss as the time to closure approached; they also increased their stake per bet. Yet they did not chase longer odds; their choices of wagers were more probabilistically conservative (i.e., short odds) compared with the controls. The changes of monetary involvement and risk preference occurred concurrently during the last few days prior to voluntary closing. Our finding of an involvement-seeking yet risk-averse tendency among self-identified problem gamblers challenges the notion that problem gamblers seek "long odds" during "chasing."

Effects of exercise and dietary habits on the occurrence of polycystic ovary syndrome over 5 years of follow-up.

PubMed

Zhang, Jing; Zhou, Kunyan; Luo, Li; Liu, Ying; Liu, Xiaofang; Xu, Liangzhi

2018-06-07

To evaluate the effects of recent and previous exercise and dietary habits on the occurrence of polycystic ovary syndrome (PCOS). The present study had a population-based case-control phase and a nested case-control phase. Women aged 12-44 years with and without PCOS were surveyed using the Semiquantitative Food Frequency Questionnaire and the International Physical Activity Questionnaire to evaluate the correlation of PCOS with recent (last 7 days) or previous (5 years ago) exercise and dietary habits. No difference in recent physical activity was found between the PCOS and control groups (case-control phase, n=1854). However, patients with PCOS had previously (5 years ago; nested case-control phase, n=1149) spent less time physical active in relation to transportation (P=0.003), housekeeping (P=0.023), walking (P<0.001), and activities of moderate intensity (P=0.008), and had spent more time sitting (P<0.001). Dietary nutrients and energy intake did not differ between the two groups (P>0.05 for all comparisons). A previous exercise habit was associated with subsequent PCOS whereas a recently acquired exercise routine was not. Women should avoid long-term sedentary lifestyle habits and focus on adding to the duration of, or enhancing the intensity of, physical activity. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Detection of diisocyanates in nesting material associated with mortality in pigeon chicks.

PubMed

Mukai, Motoko; Woods, Leslie W; Stump, Samuel; Ebel, Joseph G; Levitt, Ariana S; Frey, Margaret W; Smith, Jeanne; Uzal, Francisco A; Poppenga, Robert H; Puschner, Birgit

2014-03-01

Diisocyanates, commonly used in the production of polyurethane foams, paints, elastomers, varnishes, and coatings, are considered among the most hazardous inhalation toxicants. The present report describes 2 unusual cases of mortality in pigeon chicks associated with nesting material contaminated by diisocyanates. Case 1 was submitted by a racing pigeon breeder who had lost all the hatchlings (n = 125) following replacement of the nesting material with a different lot. All adult birds appeared healthy, and hatchability was not significantly affected, but hatchlings became lethargic and dyspneic after a day of hatch. At necropsy, dark wet lungs were found in the hatchlings. Case 2 was submitted by a show-roller pigeon breeder. In this case, the owner reported lower hatchability, and all hatchlings (approximately 100) died within 2 days of hatching with clinical signs similar to the first case. Necropsy did not reveal any significant findings. For both cases, nesting materials were screened for toxic compounds using gas chromatography-mass spectrometry. Toluene-2,4-diisocyanate (approximately 190-290 ppm) and 4,4'-methylene diphenyl diisocyanate (unquantified) were detected in the nesting pads. While there is very limited information on toxicosis in birds, there are reports of inhalant exposure of diisocyanates causing pulmonary edema and death in various mammalian species. Although cause-effect relationship of mortality and the nesting material was not established in the present cases, the presence of toxic compounds in the nesting materials is a cause for concern. Further investigation is needed to determine the prevalence and toxicity of diisocyanates-contaminated nesting material in avian species.

A new vertical grid nesting capability in the Weather Research and Forecasting (WRF) Model

DOE PAGES

Daniels, Megan H.; Lundquist, Katherine A.; Mirocha, Jeffrey D.; ...

2016-09-16

Mesoscale atmospheric models are increasingly used for high-resolution (<3 km) simulations to better resolve smaller-scale flow details. Increased resolution is achieved using mesh refinement via grid nesting, a procedure where multiple computational domains are integrated either concurrently or in series. A constraint in the concurrent nesting framework offered by the Weather Research and Forecasting (WRF) Model is that mesh refinement is restricted to the horizontal dimensions. This limitation prevents control of the grid aspect ratio, leading to numerical errors due to poor grid quality and preventing grid optimization. Here, a procedure permitting vertical nesting for one-way concurrent simulation is developedmore » and validated through idealized cases. The benefits of vertical nesting are demonstrated using both mesoscale and large-eddy simulations (LES). Mesoscale simulations of the Terrain-Induced Rotor Experiment (T-REX) show that vertical grid nesting can alleviate numerical errors due to large aspect ratios on coarse grids, while allowing for higher vertical resolution on fine grids. Furthermore, the coarsening of the parent domain does not result in a significant loss of accuracy on the nested domain. LES of neutral boundary layer flow shows that, by permitting optimal grid aspect ratios on both parent and nested domains, use of vertical nesting yields improved agreement with the theoretical logarithmic velocity profile on both domains. Lastly, vertical grid nesting in WRF opens the path forward for multiscale simulations, allowing more accurate simulations spanning a wider range of scales than previously possible.« less

A new vertical grid nesting capability in the Weather Research and Forecasting (WRF) Model

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

Daniels, Megan H.; Lundquist, Katherine A.; Mirocha, Jeffrey D.

Mesoscale atmospheric models are increasingly used for high-resolution (<3 km) simulations to better resolve smaller-scale flow details. Increased resolution is achieved using mesh refinement via grid nesting, a procedure where multiple computational domains are integrated either concurrently or in series. A constraint in the concurrent nesting framework offered by the Weather Research and Forecasting (WRF) Model is that mesh refinement is restricted to the horizontal dimensions. This limitation prevents control of the grid aspect ratio, leading to numerical errors due to poor grid quality and preventing grid optimization. Here, a procedure permitting vertical nesting for one-way concurrent simulation is developedmore » and validated through idealized cases. The benefits of vertical nesting are demonstrated using both mesoscale and large-eddy simulations (LES). Mesoscale simulations of the Terrain-Induced Rotor Experiment (T-REX) show that vertical grid nesting can alleviate numerical errors due to large aspect ratios on coarse grids, while allowing for higher vertical resolution on fine grids. Furthermore, the coarsening of the parent domain does not result in a significant loss of accuracy on the nested domain. LES of neutral boundary layer flow shows that, by permitting optimal grid aspect ratios on both parent and nested domains, use of vertical nesting yields improved agreement with the theoretical logarithmic velocity profile on both domains. Lastly, vertical grid nesting in WRF opens the path forward for multiscale simulations, allowing more accurate simulations spanning a wider range of scales than previously possible.« less

Can lung cancer risk among nickel refinery workers be explained by occupational exposures other than nickel?

PubMed

Grimsrud, Tom K; Berge, Steinar R; Haldorsen, Tor; Andersen, Aage

2005-03-01

Exposures in nickel refineries represent complex chemical mixtures, but only the effect of nickel has been evaluated quantitatively in epidemiologic studies of nickel workers. For a Norwegian refinery, time- and department-specific exposure estimates were developed for arsenic, sulfuric acid mists, and cobalt in air on the basis of personal measurements and chemical data on raw materials and process intermediates. Exposure to asbestos, as well as employment in high-risk occupations outside the refinery, were assessed. We conducted a case-control study nested in a cohort of refinery workers, with 213 cases (diagnosed 1952-1995) and 525 age-matched controls. We analyzed lung cancer risk, adjusted for smoking, by cumulative exposure and duration of work. There was a substantial association between cumulative exposure to water-soluble nickel and lung cancer risk. Weaker effects were suggested for exposure to arsenic at the refinery and for occupational exposures outside the refinery for 15 years or more. No detectable excess risk was found for refinery exposure to asbestos or sulfuric acid mists, and no dose-related increase in risk was seen from cobalt. Exposure to water-soluble nickel remained the most likely explanation for the excess lung cancer risk in the cohort. Other occupational exposures did not confound the strong dose-related effect of nickel to any appreciable degree.

Plasma matrix metalloproteinase 1, 3, and 7 levels and breast cancer risk in the Nurses' Health study.

PubMed

Aroner, Sarah A; Rosner, Bernard A; Tamimi, Rulla M; Tworoger, Shelley S; Baur, Nadja; Joos, Thomas O; Hankinson, Susan E

2014-12-01

Matrix metalloproteinases (MMPs), in particular MMP1, 3, and 7, are believed to be critical to breast cancer invasion and metastasis and also may have important functions earlier in breast carcinogenesis. However, the relationship between circulating levels of MMP1, 3, and 7 and breast cancer risk is uncertain. We examined associations between plasma MMP1, 3, and 7 and breast cancer risk in a prospective case-control study nested within the Nurses' Health Study. Blood samples were collected from 801 cases who developed breast cancer between 1992 and 2000 and 801 matched controls, and MMP levels were measured via immunofluorescence assay. No overall association was observed between any of these MMPs and breast cancer risk [top vs. bottom quintile; MMP1: odds ratio (OR) 0.9; 95 % confidence interval (CI) 0.7, 1.3; p-trend = 0.51; MMP3: OR 1.1; 95 % CI 0.8, 1.5; p-trend = 0.88; MMP7: OR = 1.2; 95 % CI 0.8, 1.7; p-trend = 0.18]. Further, findings did not significantly vary by time since blood draw, body mass index, or postmenopausal hormone use, or by breast cancer subtypes. Circulating MMP1, 3, and 7 levels do not appear to be predictive of overall breast cancer risk.

Air pollution sources and childhood asthma attacks in Catano, Puerto Rico.

PubMed

Loyo-Berríos, Nilsa I; Irizarry, Rafael; Hennessey, Joseph G; Tao, Xuguang Grant; Matanoski, Genevieve

2007-04-15

Asthma prevalence in the Cataño Air Basin of Puerto Rico is 27% for children aged 13-14 years and 45% for children aged 5-6 years. There is concern that these rates are related to air pollution. The authors conducted a nested case-control study to evaluate whether proximity to air pollution point sources was associated with increased risk of asthma attacks. For 1997-2001, 1,382 asthma-related medical visits (International Classification of Diseases, Ninth Revision, codes 493 and 493.9) in children under 17 were identified through health insurance claims. Controls were children with no asthma attacks who were randomly selected from enrollees in two health insurance companies by incidence density sampling (1:5) and matched to cases on gender, age, insurance company, and event date. The distance from a point source to the subject's residence area represented a surrogate exposure measurement. Odds ratios for a 1-km decrease in distance were obtained by conditional logistic regression. Risk of asthma attack was associated with residing near a grain mill (odds ratio (OR) = 1.35), petroleum refinery (OR = 1.44), asphalt plant (OR = 1.23), or power plant (OR = 1.28) (all p's < 0.05). Residence near major air emissions sources (>100 tons/year) increased asthma attack risk by 108% (p < 0.05). These results showed that proximity to some air pollution sources is associated with increased risks of asthma attacks.

Metabolic Mediators of the Association Between Adult Weight Gain and Colorectal Cancer: Data From the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

PubMed Central

Aleksandrova, Krasimira; Schlesinger, Sabrina; Fedirko, Veronika; Jenab, Mazda; Bueno-de-Mesquita, Bas; Freisling, Heinz; Romieu, Isabelle; Pischon, Tobias; Kaaks, Rudolf; Gunter, Marc J.; Dahm, Christina C.; Overvad, Kim; Rostgaard-Hansen, Agnetha Linn; Tjønneland, Anne; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Agnoli, Claudia; Mattiello, Amalia; Bradbury, Kathryn; Khaw, Kay-Tee; Riboli, Elio; Boeing, Heiner

2017-01-01

Abstract Evidence indicates that gaining weight in adult life is associated with an elevated risk of colorectal cancer; however, biological mechanisms that may explain this association remain unclear. We evaluated the mediation effect of 20 different biomarkers on the relationship between adult weight gain and colorectal cancer, using data from a prospective nested case-control study of 452 incident cases diagnosed between 1992 and 2003 and matched within risk sets to 452 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The proportions of mediated effects (%) were estimated on the basis of differences in percent effect changes in conditional logistic regression models with and without additional adjustment for individual biomarkers. Greater adult weight gain (≥300 g/year vs. <300 g/year) was associated with a higher risk of colon cancer (multivariable-adjusted relative risk = 1.54, 95% confidence interval: 1.07, 2.24) but not rectal cancer (relative risk = 1.07, 95% confidence interval: 0.68, 1.66). This association was accounted for mostly by attained waist circumference (reduction of 61%) and by the biomarkers soluble leptin receptor (reduction of 43%) and glycated hemoglobin (reduction of 28%). These novel data suggest that the observed association between adult weight gain and colon cancer could be primarily explained by attained abdominal fatness and biomarkers of metabolic dysfunction. PMID:28387787

Risk of treatment-related esophageal cancer among breast cancer survivors

PubMed Central

Morton, L. M.; Gilbert, E. S.; Hall, P.; Andersson, M.; Joensuu, H.; Vaalavirta, L.; Dores, G. M.; Stovall, M.; Holowaty, E. J.; Lynch, C. F.; Curtis, R. E.; Smith, S. A.; Kleinerman, R. A.; Kaijser, M.; Storm, H. H.; Pukkala, E.; Weathers, R. E.; Linet, M. S.; Rajaraman, P.; Fraumeni, J. F.; Brown, L. M.; van Leeuwen, F. E.; Fossa, S. D.; Johannesen, T. B.; Langmark, F.; Lamart, S.; Travis, L. B.; Aleman, B. M. P.

2012-01-01

Background Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use. Design Nested case–control study of esophageal cancer among 289 748 ≥5-year survivors of female breast cancer from five population-based cancer registries (252 cases, 488 individually matched controls), with individualized radiation dosimetry and information abstracted from medical records. Results The largest contributors to esophageal radiation exposure were supraclavicular and internal mammary chain treatments. Esophageal cancer risk increased with increasing radiation dose to the esophageal tumor location (Ptrend < 0.001), with doses of ≥35 Gy associated with an odds ratio (OR) of 8.3 [95% confidence interval (CI) 2.7–28]. Patients with hormonal therapy ≤5 years preceding esophageal cancer diagnosis had lower risk (OR = 0.4, 95% CI 0.2–0.8). Based on few cases, alkylating agent chemotherapy did not appear to affect risk. Our data were consistent with a multiplicative effect of radiation and other esophageal cancer risk factors (e.g. smoking). Conclusions Esophageal cancer is a radiation dose-related complication of radiotherapy for breast cancer, but absolute risk is low. At higher esophageal doses, the risk warrants consideration in radiotherapy risk assessment and long-term follow-up. PMID:22745217

Tissue factor pathway inhibitor, activated protein C resistance, and risk of ischemic stroke due to postmenopausal hormone therapy

PubMed Central

Rossouw, Jacques E; Johnson, Karen C; Pettinger, Mary; Cushman, Mary; Sandset, Per Morten; Kuller, Lewis; Rosendaal, Frits; Rosing, Jan; Wasserthal-Smoller, Sylvia; Martin, Lisa W; Manson, JoAnn E; Lakshminarayan, Kamakshi; Merino, Jose G; Lynch, John

2012-01-01

Background and Purpose To test whether changes in plasma tissue factor pathway inhibitor (TFPI) levels or activated protein C resistance (normalized APC resistance ratio, nAPCsr) modify the increased risk of ischemic stroke due to postmenopausal hormone therapy (PHT). Methods Nested case-control study of 455 cases of ischemic stroke and 565 matched controls in the Women’s Health Initiative trials of PHT. Results Baseline free TFPI was associated with ischemic stroke risk, OR (95% CI) per SD increase = 1.17 (1.01, 1.37, p=0.039, but baseline nAPCsr was not, OR per SD increase = 0.89 (0.75, 1.05), p=0.15. Baseline TFPI levels and nAPCsr did not modify the effect of PHT on ischemic stroke. Treatment-induced mean changes of -28% in free TFPI and +65% in nAPCsr did not change the risk of ischemic stroke (interaction p = 0.452 and 0.971 respectively). In subgroup analyses baseline nAPCsr was inversely associated with lacunar strokes, OR per SD increase = 0.74 (0.57, 0.96), p=0.025, and baseline free TFPI interacted with treatment to increase large vessel atherosclerotic strokes, p=0.008. Conclusions Pro-coagulant changes in TFPI or nAPCsr do not modify the increased ischemic stroke risk due to PHT. PMID:22363056

Serum IGFBP-2 and Risk of Atypical Hyperplasia of the Breast.

PubMed

Catsburg, Chelsea; Gunter, Marc J; Tinker, Lesley; Chlebowski, Rowan T; Pollak, Michael; Strickler, Howard D; Cote, Michele L; Page, David L; Rohan, Thomas E

2015-01-01

Atypical hyperplasia of the breast (AH) is associated with increased risk of subsequent invasive breast cancer, yet little is known about the etiology of AH. Insulin-like growth factor binding protein 2 (IGFBP-2) may contribute to the development of AH due to its proliferative effects on mammary tissue. We conducted a nested case-control study of postmenopausal women enrolled in Women's Health Initiative-Clinical Trial. Cases were 275 women who developed incident AH during follow-up, individually (1 : 1) matched to controls. Levels of IGFBP-2 were determined from fasting serum collected at baseline. Multivariable conditional logistic regression models were used to estimate odds ratios for the association of IGFBP-2 with risk of AH. Serum IGFBP-2 was associated with a nonsignificant decrease in risk for AH, when comparing the highest quartile to lowest quartile (OR = 0.65; 95% CI = 0.32-1.31). This decrease in risk was most evident when analyses were restricted to nondiabetic, nonusers of hormone therapy (OR = 0.33, 95% CI = 0.13-0.86, p trend = 0.06) and nondiabetic women who were overweight or obese (OR = 0.43, 95% CI = 0.18-1.03, p trend = 0.05). Results from this study provide some support for an inverse association between serum IGFBP2 levels and risk of AH, particularly in nondiabetic women who are overweight or obese. Further studies are required to confirm these results.

Matched samples logistic regression in case-control studies with missing values: when to break the matches.

PubMed

Hansson, Lisbeth; Khamis, Harry J

2008-12-01

Simulated data sets are used to evaluate conditional and unconditional maximum likelihood estimation in an individual case-control design with continuous covariates when there are different rates of excluded cases and different levels of other design parameters. The effectiveness of the estimation procedures is measured by method bias, variance of the estimators, root mean square error (RMSE) for logistic regression and the percentage of explained variation. Conditional estimation leads to higher RMSE than unconditional estimation in the presence of missing observations, especially for 1:1 matching. The RMSE is higher for the smaller stratum size, especially for the 1:1 matching. The percentage of explained variation appears to be insensitive to missing data, but is generally higher for the conditional estimation than for the unconditional estimation. It is particularly good for the 1:2 matching design. For minimizing RMSE, a high matching ratio is recommended; in this case, conditional and unconditional logistic regression models yield comparable levels of effectiveness. For maximizing the percentage of explained variation, the 1:2 matching design with the conditional logistic regression model is recommended.

Social Hackers: Integration in the Host Chemical Recognition System by a Paper Wasp Social Parasite

NASA Astrophysics Data System (ADS)

Turillazzi, S.; Sledge, M. F.; Dani, F. R.; Cervo, R.; Massolo, A.; Fondelli, L.

Obligate social parasites in the social insects have lost the worker caste and the ability to establish nests. As a result, parasites must usurp a host nest, overcome the host recognition system, and depend on the host workers to rear their offspring. We analysed cuticular hydrocarbon profiles of live parasite females of the paper wasp social parasite Polistes sulcifer before and after usurpation of host nests, using the non-destructive technique of solid-phase micro-extraction. Our results reveal that hydrocarbon profiles of parasites change after usurpation of host nests to match the cuticular profile of the host species. Chemical evidence further shows that the parasite queen changes the odour of the nest by the addition of a parasite-specific hydrocarbon. We discuss the possible role of this in the recognition and acceptance of the parasite and its offspring in the host colony.

Social hackers: integration in the host chemical recognition system by a paper wasp social parasite.

PubMed

Turillazzi, S; Sledge, M F; Dani, F R; Cervo, R; Massolo, A; Fondelli, L

2000-04-01

Obligate social parasites in the social insects have lost the worker caste and the ability to establish nests. As a result, parasites must usurp a host nest, overcome the host recognition system, and depend on the host workers to rear their offspring. We analysed cuticular hydrocarbon profiles of live parasite females of the paper wasp social parasite Polistes sulcifer before and after usurpation of host nests, using the non-destructive technique of solid-phase micro-extraction. Our results reveal that hydrocarbon profiles of parasites change after usurpation of host nests to match the cuticular profile of the host species. Chemical evidence further shows that the parasite queen changes the odour of the nest by the addition of a parasite-specific hydrocarbon. We discuss the possible role of this in the recognition and acceptance of the parasite and its offspring in the host colony.

[The case-case-time-control study design].

PubMed

Wang, Jing; Zhuo, Lin; Zhan, Siyan

2014-12-01

Although the 'self-matched case-only studies' (such as the case-cross-over or self-controlled case-series method) can control the time-invariant confounders (measured or unmeasured) through design of the study, however, they can not control those confounders that vary with time. A bidirectional case-crossover design can be used to adjust the exposure-time trends. In the areas of pharmaco-epidemiology, illness often influence the future use of medications, making a bidirectional study design problematic. Suissa's case-time-control design combines the case-crossover and the case-control design which could adjust for exposure-trend bias, but the control group may reintroduce selection bias, if the matching does not go well. We propose a "case-case-time-control" design which is an extension of the case-time-control design. However, rather than using a sample of external controls, we choose those future cases as controls for current cases to counter the bias that arising from temporal trends caused by exposure to the target of interest. In the end of this article we will discuss the strength and limitations of this design based on an applied example.

Association of Bacterial Vaginosis With Chlamydia and Gonorrhea Among Women in the U.S. Army.

PubMed

Bautista, Christian T; Wurapa, Eyako K; Sateren, Warren B; Morris, Sara M; Hollingsworth, Bruce P; Sanchez, Jose L

2017-05-01

Bacterial vaginosis (BV) is a common vaginal condition in women of reproductive age, which has been associated with Chlamydia trachomatis and Neisseria gonorrhoeae among commercial sex workers and women attending sexually transmitted infection clinics. Pathogen-specific associations between BV and other sexually transmitted infections among U.S. military women have not been investigated. A population-based, nested case-control study was conducted of all incident chlamydia and gonorrhea cases reported to the Defense Medical Surveillance System during 2006-2012. Using a density sampling approach, for each chlamydia or gonorrhea case, 10 age-matched (±1 year) controls were randomly selected from those women who were never diagnosed with these infections. Incidence rate ratios were estimated using conditional logistic regression. Statistical analysis was carried out in December 2015. A total of 37,149 chlamydia cases and 4,987 gonorrhea cases were identified during the study period. Antecedent BV was associated with an increased risk of subsequent chlamydia (adjusted incidence rate ratio=1.51; 95% CI=1.47, 1.55) and gonorrhea (adjusted incidence rate ratio=2.42; 95% CI=2.27, 2.57) infections. For every one additional episode of BV, the risk of acquiring chlamydia and gonorrhea infections increased by 13% and 26%, respectively. A monotonic dose-response relationship was also noted between antecedent BV and subsequent chlamydia and gonorrhea infection. In addition, an effect modification on the additive scale was found between BV and African-American race for gonorrhea, but not for chlamydia. Among U.S. Army women, antecedent BV is associated with an increased risk of subsequent chlamydia and gonorrhea infection. Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.

Risk and protective factors for meningococcal disease in adolescents: matched cohort study.

PubMed

Tully, Joanna; Viner, Russell M; Coen, Pietro G; Stuart, James M; Zambon, Maria; Peckham, Catherine; Booth, Clare; Klein, Nigel; Kaczmarski, Ed; Booy, Robert

2006-02-25

To examine biological and social risk factors for meningococcal disease in adolescents. Prospective, population based, matched cohort study with controls matched for age and sex in 1:1 matching. Controls were sought from the general practitioner. Six contiguous regions of England, which represent some 65% of the country's population. 15-19 year olds with meningococcal disease recruited at hospital admission in six regions (representing 65% of the population of England) from January 1999 to June 2000, and their matched controls. Blood samples and pernasal and throat swabs were taken from case patients at admission to hospital and from cases and matched controls at interview. Data on potential risk factors were gathered by confidential interview. Data were analysed by using univariate and multivariate conditional logistic regression. 144 case control pairs were recruited (74 male (51%); median age 17.6). 114 cases (79%) were confirmed microbiologically. Significant independent risk factors for meningococcal disease were history of preceding illness (matched odds ratio 2.9, 95% confidence interval 1.4 to 5.9), intimate kissing with multiple partners (3.7, 1.7 to 8.1), being a university student (3.4, 1.2 to 10) and preterm birth (3.7, 1.0 to 13.5). Religious observance (0.09, 0.02 to 0.6) and meningococcal vaccination (0.12, 0.04 to 0.4) were associated with protection. Activities and events increasing risk for meningococcal disease in adolescence are different from in childhood. Students are at higher risk. Altering personal behaviours could moderate the risk. However, the development of further effective meningococcal vaccines remains a key public health priority.

The relationship between weight gain during pregnancy and urinary tract infections in pregnant women of Shahrekord, by using the “Nested case-control study”, in 2013

PubMed Central

Rejali, Mehri; Ahmadi, Seyede Soghra; Hassanzadeh, Akbar; Yazdani, Rezvan; Ahmadi, Seyede Nafiseh

2015-01-01

Background and Objectives: Pregnancy is one of the most important and risky periods in mothers and the fetus life, which plays a key role in health and social activity of the person, family and community. This study is trying to see if there is a relation between increasing weight and urinary tract infection (UTI) in pregnancy by using the open nested case-control study in the city of Shahrekord. Materials and Methods: In a nested case-control study, one cohort including 832 patients was examined until week 26 to 30 of pregnancy and their UTIs were studied. The required information was collected by examining the health records of pregnant women and completion of the data registration forms. Data collection was controlled by using SPSS and analyzed by using an independent t-test, Chi-square test, Pearson correlation and logistic regression. Results: According to the results of the cohort study with 832 individuals, average weight gain of the group with a UTI was 11.13 ± 3.9 kg and it was 10.63 ± 3.9 kg in the group without UTI, showing no statistically significant difference (P = 0.245). According to the results, genitourinary problems had the highest predictive value for UTIs and the numbers of infertility and the childbirth variables were in the second and third positions, respectively. Conclusion: According to the results study we can conclude that screening and treatment of UTIs have been on time and appropriate in health systems of the city of Shahrekord which have lead to the reduction of infant and maternal diseases even with the condition in having no UTI, and continuing this process for screening and treatment is recommended. PMID:27462626

The relationship between weight gain during pregnancy and urinary tract infections in pregnant women of Shahrekord, by using the "Nested case-control study", in 2013.

PubMed

Rejali, Mehri; Ahmadi, Seyede Soghra; Hassanzadeh, Akbar; Yazdani, Rezvan; Ahmadi, Seyede Nafiseh

2015-01-01

Pregnancy is one of the most important and risky periods in mothers and the fetus life, which plays a key role in health and social activity of the person, family and community. This study is trying to see if there is a relation between increasing weight and urinary tract infection (UTI) in pregnancy by using the open nested case-control study in the city of Shahrekord. In a nested case-control study, one cohort including 832 patients was examined until week 26 to 30 of pregnancy and their UTIs were studied. The required information was collected by examining the health records of pregnant women and completion of the data registration forms. Data collection was controlled by using SPSS and analyzed by using an independent t-test, Chi-square test, Pearson correlation and logistic regression. According to the results of the cohort study with 832 individuals, average weight gain of the group with a UTI was 11.13 ± 3.9 kg and it was 10.63 ± 3.9 kg in the group without UTI, showing no statistically significant difference (P = 0.245). According to the results, genitourinary problems had the highest predictive value for UTIs and the numbers of infertility and the childbirth variables were in the second and third positions, respectively. According to the results study we can conclude that screening and treatment of UTIs have been on time and appropriate in health systems of the city of Shahrekord which have lead to the reduction of infant and maternal diseases even with the condition in having no UTI, and continuing this process for screening and treatment is recommended.

Correlation between cognitive impairment during the acute phase of first cerebral infarction and development of long-term pseudobulbar affect

PubMed Central

Wang, Yuan; Wang, Yuliang; Ma, Wenbin; Lu, Shujun; Chen, Jinbo; Cao, Lili

2018-01-01

Purpose The relationship between cognitive impairment during the acute phase of first cerebral infarction and the development of long-term pseudobulbar affect (PBA) has not been elucidated. Therefore, in this study, we aimed to determine if cognitive impairment during the acute phase of cerebral infarction will increase the risk of long-term post-infarction PBA. Patients and methods This was a nested case–control study using a prospective approach. A consecutive multicenter matched 1:1 case–control study of cognitive impairment cases following acute cerebral infarction (N=26) with 26 sex-, education years-, and age-matched controls. Univariate and multivariate conditional logistic regression analyses were performed to study the clinical features and changes in cognitive domain as well as the risk factors for PBA. Results Long-term PBA was independently predicted by low Montreal cognitive assessment (MoCA) scores at baseline. Multivariable regression models showed that post-infarction low MoCA scores remained independent predictors of long-term PBA (odds ratio [OR]=0.72; 95% confidence interval [CI]=0.54–0.95; P=0.018). Among all cognitive disorders, digit span test (DST) scores (OR=0.39; 95% CI=0.16–0.91, P=0.030), StroopC time (OR=1.15; 95% CI=1.01–1.31; P=0.037), and clock-drawing task (CDT) scores (OR=0.62; 95% CI=0.42–0.90; P=0.013) were found to be the independent risk factors for PBA. Conclusion Cognitive impairment during the acute phase of cerebral infarction increased the risk of cerebral infarction-induced long-term PBA. Development of PBA was closely associated with executive function, attention, and visuospatial disorder. PMID:29636612

Application of STR markers in wildlife forensic casework involving Australian black-cockatoos (Calyptorhynchus spp.).

PubMed

White, Nicole E; Dawson, Rick; Coghlan, Megan L; Tridico, Silvana R; Mawson, Peter R; Haile, James; Bunce, Michael

2012-09-01

Parrots and cockatoos are highly prized aviary birds and the demands for such species has fuelled their illegal trade and harvest from the wild. Here we report on three forensic case studies involving black-cockatoos (Calyptorhynchus spp.) endemic to Australia. These cases involve suspected poaching and illegal killing of endangered red- and white-tailed black-cockatoos. Through the prior development of 20 polymorphic microsatellite loci and population databases for white- and red-tailed black-cockatoos, the tools are available to conduct high-resolution paternity and individual identity testing. In one case, we matched a red-tailed black-cockatoo nestling to a tree hollow from which it was poached through the use of DNA from eggshell recovered from the nest. For the second case, we utilized our provenance population database (nest sites), and identified the kinship and geographic origin of a white-tailed black-cockatoo, which was illegally harvested from the wild. The third case determined the number individual white-tailed black-cockatoos allegedly shot at a fruit grower's orchard from body part remains. These genetic investigations highlight the significance and statistical confidence of DNA profiling and associated databases for endangered taxa, such as exotic birds. Our cockatoo population databases are the first of their kind in Australia, and demonstrate the efficacy of such approaches to identify such illegal activity. With a robust set of genetic markers and methodologies in place, we aim to broaden our population databases to include other cockatoo species of conservation concern. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

FVCOM one-way and two-way nesting using ESMF: Development and validation

NASA Astrophysics Data System (ADS)

Qi, Jianhua; Chen, Changsheng; Beardsley, Robert C.

2018-04-01

Built on the Earth System Modeling Framework (ESMF), the one-way and two-way nesting methods were implemented into the unstructured-grid Finite-Volume Community Ocean Model (FVCOM). These methods help utilize the unstructured-grid multi-domain nesting of FVCOM with an aim at resolving the multi-scale physical and ecosystem processes. A detail of procedures on implementing FVCOM into ESMF was described. The experiments were made to validate and evaluate the performance of the nested-grid FVCOM system. The first was made for a wave-current interaction case with a two-domain nesting with an emphasis on qualifying a critical need of nesting to resolve a high-resolution feature near the coast and harbor with little loss in computational efficiency. The second was conducted for the pseudo river plume cases to examine the differences in the model-simulated salinity between one-way and two-way nesting approaches and evaluate the performance of mass conservative two-way nesting method. The third was carried out for the river plume case in the realistic geometric domain in Mass Bay, supporting the importance for having the two-way nesting for coastal-estuarine integrated modeling. The nesting method described in this paper has been used in the Northeast Coastal Ocean Forecast System (NECOFS)-a global-regional-coastal nesting FVCOM system that has been placed into the end-to-end forecast and hindcast operations since 2007.

Prevalence of non-organ-specific autoantibodies and chronic liver disease in the general population: a nested case-control study of the Dionysos cohort

PubMed Central

Lenzi, M; Bellentani, S; Saccoccio, G; Muratori, P; Masutti, F; Muratori, L; Cassani, F; Bianchi, F; Tiribelli, C

1999-01-01

BACKGROUND—Several retrospective and prospective studies report an increased prevalence of non-organ-specific autoantibodies (NOSAs) in patients with hepatitis C virus (HCV) related chronic liver disease (CLD). Some of the data so far available are controversial and the true prevalence of NOSAs in the general population is still not known.
AIM—To explore the prevalence of NOSAs, their relation to different HCV genotypes, and the presence and severity of CLD in the general population of Northern Italy.
PATIENTS—All 226 anti-HCV positive and 87 hepatitis B surface antigen (HBsAg) positive patients of the Dionysos cohort study were analysed and compared with sex and age matched cases (226) negative for both anti-HCV antibody and HBsAg selected from the same cohort.
METHODS—Sera tested for the presence of NOSAs (anti-nuclear antibody (ANA), anti-smooth muscle antibody (SMA), and anti-liver/kidney microsomes type 1 antibody (LKM1)) were screened by indirect immunofluorescence at a 1:40 serum dilution. HCV RNA and HCV genotypes were also determined by nested polymerase chain reaction (PCR) of the 5' non-coding region and by PCR amplification of the core region with type specific primers.
RESULTS—The overall prevalence of NOSA reactivity was significantly higher in anti-HCV positive subjects than in both normal and pathological controls (25% v 6% and 7% respectively, p<0.05). ANA, SMA, and LKM1 occurred in 16, 10, and 1.3% of cases respectively. No specific association between NOSAs and a specific HCV genotype was found. NOSAs were found more often associated with more than one genotype (35.7%) and with untypable genotypes (34.6%), although the association was not statistically significant. NOSAs were associated with HCV RNA and CLD but not with the presence of cirrhosis and/or hepatocellular carcinoma. On univariate analysis, NOSA reactivity was independently associated with abnormal alanine aminotransferase (p<0.01) and γ-glutamyltranspeptidase levels (p<0.05). The risk for the presence of NOSAs was 5.1 times higher in anti-HCV subjects than in controls.
CONCLUSIONS—In the general population the prevalence of NOSAs is higher in anti-HCV positive subjects than in normal or disease controls. Moreover NOSAs are associated with CLD and with a more active disease in terms of alanine aminotransferase activity.


Keywords: non-organ-specific autoantibodies; hepatitis C virus genotypes; chronic liver disease; cohort study; prevalence PMID:10446115

Sitting in the sun: Nest microhabitat affects incubation temperatures in seabirds.

PubMed

Hart, Lorinda A; Downs, Colleen T; Brown, Mark

2016-08-01

During incubation parent birds are committed to a nest site and endure a range of ambient conditions while regulating egg temperatures. Using artificial eggs containing temperature loggers alongside ambient temperature (Ta) controls, incubation profiles were determined for four tropical seabird species at different nest site locations. Camera traps were used for ad-hoc behavioural incubation observations. Eggs experienced a range of temperatures during incubation and varied significantly between species and in some cases between different microhabitats within a species. Such variation has important consequences in the phenotypic expression of both physical and physiological traits of chicks, and ultimately species fitness. Exposed nest sites were more strongly correlated to Tas. Camera traps highlighted different incubation strategies employed by these species that could be related to trade-offs in predator defence, feeding habits, and temperature regulation of eggs. This study provides evidence that species with similar breeding habits could be affected by environmental stressors in similar ways and that the differences shown in nest site selection could negate some of these effects. We propose that habitats providing suitable nest microclimates will become increasingly important for the successful breeding of seabird species, particularly under predicted climate change scenarios. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bird's Nest Filter Causing Symptomatic Hydronephrosis Following Transmural Penetration of the Inferior Vena Cava

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

Stacey, C.S., E-mail: cheika@doctors.org.uk; Manhire, A.R.; Rose, D.H.

2004-01-15

We report a case of symptomatic hydronephrosis caused by transcaval penetration of a Bird's Nest filter. Perforation of the wall of the inferior vena cava (IVC) following insertion of a caval filter is a well-recognized complication. Whilst two cases of hydronephrosis have been described with Greenfield filters, no case involving a Bird's Nest filter has been reported previously.

Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana

PubMed Central

Harris, Vanessa C.; Armah, George; Fuentes, Susana; Korpela, Katri E.; Parashar, Umesh; Victor, John C.; Tate, Jacqueline; de Weerth, Carolina; Giaquinto, Carlo; Wiersinga, Willem Joost; Lewis, Kristen D. C.; de Vos, Willem M.

2017-01-01

Background. Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings. Methods. We conducted a nested, case-control study comparing prevaccination, fecal microbiome compositions between 6-week old, matched RVV responders and nonresponders in rural Ghana. These infants' microbiomes were then compared with 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV responders. Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip. Results. We analyzed findings in 78 Ghanaian infants, including 39 RVV responder and nonresponder pairs. The overall microbiome composition was significantly different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian responders were more similar to Dutch infants than nonresponders (P = .002). RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and Ghanaian nonresponders (FDR, 0.002 vs 0.009). Conclusions. The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries. PMID:27803175

PPM1A Methylation Is Associated With Vascular Recurrence in Aspirin-Treated Patients.

PubMed

Gallego-Fabrega, Cristina; Carrera, Caty; Reny, Jean-Luc; Fontana, Pierre; Slowik, Agnieszka; Pera, Joanna; Pezzini, Alessandro; Serrano-Heras, Gemma; Segura, Tomás; Bin Dukhyil, Abdul-Aziz A; Martí-Fàbregas, Joan; Muiño, Elena; Cullell, Natalia; Montaner, Joan; Krupinski, Jerzy; Fernandez-Cadenas, Israel

2016-07-01

Despite great efforts by pharmacogenetic studies, the causes of aspirin failure to prevent the recurrence of ischemic events remain unclear. Our aim was to study whether epigenetics could be associated with the risk of vascular recurrence in aspirin-treated stroke patients. We performed an epigenetic joint analysis study in 327 patients treated with aspirin. In the discovery stage, we performed a nested case-control study in 38 matched ischemic stroke patients in whom 450 000 methylation sites were analyzed. Nineteen patients presented vascular recurrence after stroke, and 19 matched patients did not present vascular recurrence during the first year of follow-up. In a second stage, 289 new patients were analyzed by EpiTYPER. The following 3 differentially methylated candidate CpG sites, were identified in the discovery stage and analyzed in the second stage: cg26039762 (P=9.69×10(-06), RAF1), cg04985020 (P=3.47×10(-03), PPM1A), and cg08419850 (P=3.47×10(-03), KCNQ1). Joint analysis identified an epigenome-wide association for cg04985020 (PPM1A; P=1.78×10(-07)), with vascular recurrence in patients treated with aspirin. The pattern of differential methylation in PPM1A is associated with vascular recurrence in aspirin-treated stroke patients. © 2016 American Heart Association, Inc.

Morphological Features in Children with Autism Spectrum Disorders: A Matched Case-Control Study

ERIC Educational Resources Information Center

Ozgen, Heval; Hellemann, Gerhard S.; Stellato, Rebecca K.; Lahuis, Bertine; van Daalen, Emma; Staal, Wouter G.; Rozendal, Marije; Hennekam, Raoul C.; Beemer, Frits A.; van Engeland, Herman

2011-01-01

This study was designed to examine morphological features in a large group of children with autism spectrum disorder versus normal controls. Amongst 421 patients and 1,007 controls, 224 matched pairs were created. Prevalence rates and odds ratios were analyzed by conditional regression analysis, McNemar test or paired t-test matched pairs.…

Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT

PubMed Central

2010-01-01

Introduction We used the data of the German biologics register RABBIT, a nationwide prospective cohort study, to investigate the risk of new or recurrent malignancy in patients with rheumatoid arthritis (RA) receiving biologics compared to conventional disease modifying anti-rheumatic drugs (DMARDs). Methods The analysis was based on patients with RA enrolled in RABBIT at the start of a biologic or conventional DMARD therapy between 01 May 2001 and 31 December 2006. Incidences of first or recurrent malignancies were analysed separately. A nested case-control design was used to investigate the risk of developing a first malignancy. Matching criteria were: age, gender, follow-up time, disease activity score based on 28 joint counts (DAS28) at study entry, smoking status, and selected chronic co-morbid conditions (obstructive or other lung disease, kidney, liver or gastrointestinal disease, psoriasis). Results A prior malignancy was reported in 122 out of 5,120 patients. Fifty-eight of these patients had received anti-TNFα agents, 9 anakinra, and 55 conventional DMARDs at study entry. In 14 patients (ever exposed to anti-TNFα: eight, to anakinra: one) 15 recurrent cancers were observed. The average time period since the onset of the first malignancy was nine years. Crude recurrence rates per 1,000 patient-years (pyrs) were 45.5 for patients exposed to anti-TNFα agents, 32.3 for anakinra patients and 31.4 for patients exposed to DMARDs only (Incidence rate ratio anti-TNFα vs. DMARD = 1.4, P = 0.6.). In patients without prior cancer, 74 patients (70% female, mean age: 61.3) developed a first malignancy during the observation. This corresponds to an incidence rate (IR) of 6.0/1,000 pyrs. Forty-four of these patients were ever exposed to anti-TNFα treatment (IR = 5.1/1,000 pyrs). In a nested case-control study comparing cancer patients to cancer-free controls, 44 of the cancer patients and 44 of the cancer-free controls were ever exposed to anti-TNFα agents (P = 1.0). Conclusions No significant differences in the overall incidence of malignancies in patients exposed or unexposed to anti-TNFα or anakinra treatment were found. The same applied to the risk of recurrent malignancies. However, in particular this last finding needs further validation in larger data sets. PMID:20064207

Nutritional adequacy of a cows' milk exclusion diet in infancy.

PubMed

Maslin, Kate; Oliver, Erin M; Scally, Karen S; Atkinson, Josh; Foote, Keith; Venter, Carina; Roberts, Graham; Grimshaw, Kate E C

2016-01-01

Infants with suspected cows' milk allergy are required to follow a strict milk exclusion diet which may lead to nutritional deficiencies, especially if not supervised by a healthcare professional. The aim of this study was to assess the nutritional adequacy of a cows' milk exclusion diet in a group of UK infants over a period of 6 months. Participants in this study are a subgroup of the Prevalence of Infant Food Allergy study, a prospective food allergy birth cohort study from the South of England. Each infant consuming a milk free diet, following advice from a specialist allergy dietitian, was matched to two control infants who were consuming an unrestricted diet, forming a nested matched case-control study. Detailed food diaries completed prospectively for 1 week per month over a 5 month period, were coded and analysed according to a standard protocol. The diets of 39 infants (13 milk-free and 26 controls) were assessed. Mean age at diet commencement was 14 weeks. Two of the eleven infants started on an extensively hydrolysed formula did not tolerate it and required an amino acid formula for symptom resolution. All infants had mean intakes in excess of the estimated average requirement for energy and the recommended nutrient intake (RNI) for protein, calcium, iron, selenium, zinc, vitamins A, C and E. Vitamin D intake was in excess of the RNI at all time-points, except at 44 weeks of age. Across the study period, selenium intake was higher for infants consuming a milk free diet whilst vitamin C intake was higher for infants consuming an unrestricted diet. Differences were found between the two groups for protein, calcium, iron and vitamin E intakes at differing time points. This study demonstrated that although infants consuming a milk-free diet have a nutritional intake that is significantly different to matched controls who are eating an unrestricted diet, this difference is not constant and it is not seen for all nutrients. Further research in infants without dietetic input is needed to explore the nutritional implications of unsupervised cows' milk exclusion diets.

Risk factors for idiopathic intracranial hypertension in men: a case-control study

PubMed Central

Fraser, J. Alexander; Bruce, Beau B.; Rucker, Janet; Fraser, Lisa-Ann; Atkins, Edward J.; Newman, Nancy J.; Biousse, Valérie

2009-01-01

Objective To identify risk factors for idiopathic intracranial hypertension (IIH) in men Design Case-control study. A 96-item telephone questionnaire, answered retrospectively, with cases recalling at the age of their diagnosis and controls recalling at the age of their corresponding case's diagnosis. Setting Outpatient clinics in two US tertiary care centers Participants The characteristics of 24 men with IIH were compared to those of 48 controls matched for sex, age, race, and World Health Organization body mass index (BMI) category. Main Outcome Measures Two previously validated questionnaires: the ADAM (Androgen Deficiency in Aging Males) questionnaire for testosterone deficiency and the Berlin questionnaire for obstructive sleep apnea (OSA), embedded within the telephone questionnaire. Analysis with Mantel-Haenszel odds ratios and mixed-effects logistic regression models accounted for matching. Results Cases and controls had similar enrollment matching characteristics. Although matching was successful by BMI category, there was a small difference between BMI values of cases and controls (cases: median 31.7, controls: median 29.9; p=0.03). After adjustment by BMI value, men with IIH were significantly more likely than controls to have a positive ADAM questionnaire for testosterone deficiency (OR: 17.4, 95% CI: 5.6-54.5; p<0.001) and significantly more likely to have either a positive Berlin questionnaire for OSA or history of diagnosed OSA (OR: 4.4, 95% CI: 1.5-12.9; p=0.03). Conclusions Men with IIH are more likely than controls to have symptoms associated with testosterone deficiency and OSA. These associations suggest a possible role for sex hormones and OSA in the pathogenesis of IIH in men. PMID:19945715

Uncertain Associations of Major Bleeding and Concurrent Use of Antiplatelet Agents and Chinese Medications: A Nested Case-Crossover Study

PubMed Central

Yam, Felix K.

2017-01-01

Despite the evidence that some commonly used Chinese medications (CMs) have antiplatelet/anticoagulant effects, many patients still used antiplatelets combined with CMs. We conducted a nested case-crossover study to examine the associations between the concomitant use of antiplatelets and CMs and major bleeding using population-based health database in Taiwan. Among the cohort of 79,463 outpatients prescribed antiplatelets (e.g., aspirin and clopidogrel) continuously, 1,209 patients hospitalized with new occurring bleeding in 2012 and 2013 were included. Those recruited patients served as their own controls to compare different times of exposure to prespecified CMs (e.g., Asian ginseng and dong quai) and antiplatelet agents. The periods of case, control 1, and control 2 were defined as 1–4 weeks, 6–9 weeks, and 13–16 weeks before hospitalization, respectively. Conditional logistic regression analyses found that concurrent use of antiplatelet drugs with any of the prespecified CMs in the case period might not significantly increase the risks of bleeding over that in the control periods (OR = 1.00, 95% CI 0.51 to 1.95 and OR = 1.13, 95% CI 0.65 to 1.97). The study showed no strong relationships between hospitalization for major bleeding events and concurrent use of antiplatelet drugs with the prespecified CMs. PMID:28831288

Symptoms of anxiety and depression during pregnancy and their association with low birth weight in Chinese women: a nested case control study.

PubMed

Yang, Shaoping; Yang, Rong; Liang, Shengwen; Wang, Jing; Weaver, Nancy L; Hu, Ke; Hu, Ronghua; Trevathan, Edwin; Huang, Zhen; Zhang, Yiming; Yin, Ting; Chang, Jen Jen; Zhao, Jinzhu; Shen, Longjiao; Dong, Guanghui; Zheng, Tongzhang; Xu, Shunqing; Qian, Zhengmin; Zhang, Bin

2017-04-01

This study is a nested case control study from a population-based cohort study conducted in Wuhan, China. The aim is to estimate the association between symptoms of depression during pregnancy (DDP), anxiety during pregnancy(ADP), and depression with anxiety during pregnancy (DADP) and low birth weight (LBW) and to examine the extent to which preterm birth (PTB) moderates these associations. Logistic regression analyses were used to model associations between DDP, ADP, and DADP and LBW. Models were stratified by the presence or absence of PTB to examine moderating effects. From the cohort study, 2853 had a LBW baby (cases); 5457 pregnant women served as controls. Women with DDP or ADP only were not at higher risk of having a LBW baby, but DADP was associated with increased risk of LBW (crude OR 1.41, 95% CI 1.17-1.70; adjusted OR 1.29, 95% CI 1.07-1.57), and the significant association was particularly evident between DADP and LBW in PTB, but not in full-term births. Our data suggests that DADP is related to an increased risk of LBW and that this association is most present in PTBs.

The use of antidepressants and the risk of haemorrhagic stroke: a nested case control study

PubMed Central

Douglas, Ian; Smeeth, Liam; Irvine, David

2011-01-01

AIM To investigate whether selective serotonin re-uptake inhibitor (SSRI) use is associated with an increased risk of haemorrhagic stroke in a cohort of antidepressant users. METHODS We conducted a case control study, nested within a cohort of antidepressant users in the United Kingdom General Practice Research Database. A cohort of 365 195 patients prescribed either an SSRI or tricyclic antidepressant between 1992 and 2006 was identified. Three hundred and fifty-seven cases of haemorrhagic stroke were observed and 1631 control patients without haemorrhagic stroke were selected. RESULTS The primary analysis showed no evidence of an association between current SSRI or TCA use and haemorrhagic stroke. Current use of an SSRI compared with no use at the time of haemorrhagic stroke was associated with an adjusted odds ratio of 1.11 (95% confidence interval (CI) 0.82, 1.50). For current tricyclic use the equivalent odds ratio was 0.73 (0.52, 1.02). There was no evidence that prior cerebrovascular events modified the effect of either SSRIs or TCAs. CONCLUSIONS We found no evidence that SSRIs are associated with an increased risk of haemorrhagic stroke, regardless of prior history of cerebrovascular events. PMID:21143507

The Diesel Exhaust in Miners study: a nested case-control study of lung cancer and diesel exhaust.

PubMed

Silverman, Debra T; Samanic, Claudine M; Lubin, Jay H; Blair, Aaron E; Stewart, Patricia A; Vermeulen, Roel; Coble, Joseph B; Rothman, Nathaniel; Schleiff, Patricia L; Travis, William D; Ziegler, Regina G; Wacholder, Sholom; Attfield, Michael D

2012-06-06

Most studies of the association between diesel exhaust exposure and lung cancer suggest a modest, but consistent, increased risk. However, to our knowledge, no study to date has had quantitative data on historical diesel exposure coupled with adequate sample size to evaluate the exposure-response relationship between diesel exhaust and lung cancer. Our purpose was to evaluate the relationship between quantitative estimates of exposure to diesel exhaust and lung cancer mortality after adjustment for smoking and other potential confounders. We conducted a nested case-control study in a cohort of 12 315 workers in eight non-metal mining facilities, which included 198 lung cancer deaths and 562 incidence density-sampled control subjects. For each case subject, we selected up to four control subjects, individually matched on mining facility, sex, race/ethnicity, and birth year (within 5 years), from all workers who were alive before the day the case subject died. We estimated diesel exhaust exposure, represented by respirable elemental carbon (REC), by job and year, for each subject, based on an extensive retrospective exposure assessment at each mining facility. We conducted both categorical and continuous regression analyses adjusted for cigarette smoking and other potential confounding variables (eg, history of employment in high-risk occupations for lung cancer and a history of respiratory disease) to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Analyses were both unlagged and lagged to exclude recent exposure such as that occurring in the 15 years directly before the date of death (case subjects)/reference date (control subjects). All statistical tests were two-sided. We observed statistically significant increasing trends in lung cancer risk with increasing cumulative REC and average REC intensity. Cumulative REC, lagged 15 years, yielded a statistically significant positive gradient in lung cancer risk overall (P (trend) = .001); among heavily exposed workers (ie, above the median of the top quartile [REC ≥ 1005 μg/m(3)-y]), risk was approximately three times greater (OR = 3.20, 95% CI = 1.33 to 7.69) than that among workers in the lowest quartile of exposure. Among never smokers, odd ratios were 1.0, 1.47 (95% CI = 0.29 to 7.50), and 7.30 (95% CI = 1.46 to 36.57) for workers with 15-year lagged cumulative REC tertiles of less than 8, 8 to less than 304, and 304 μg/m(3)-y or more, respectively. We also observed an interaction between smoking and 15-year lagged cumulative REC (P (interaction) = .086) such that the effect of each of these exposures was attenuated in the presence of high levels of the other. Our findings provide further evidence that diesel exhaust exposure may cause lung cancer in humans and may represent a potential public health burden.

Whole-Blood Nested-PCR Amplification of M. leprae-Specific DNA for Early Diagnosis of Leprosy

PubMed Central

Wen, Yan; Xing, Yan; Yuan, Lian-Chao; Liu, Jian; Zhang, Ying; Li, Huan-Ying

2013-01-01

We evaluated the sensitivity and specificity of a nested-polymerase chain reaction (PCR) method for detection of Mycobacterium leprae DNA from whole blood. Whole-blood specimens were subjected to nested-PCR amplification of M. leprae repeat DNA sequences in 49 multibacillary (MB) and 30 paucibacillary (PB) leprosy patients, 96 household contacts (HHCs), 18 tuberculosis (TB) patients, and 35 normal healthy individuals. M. leprae DNA was detected in 95.92% (47/49) of MB, 70% (21/30) of PB, and 6.25% (6/96) of HHC, but it was not detected in 18 TB or 35 normal controls. The sensitivities of the anti-bovine serum albumin (ND-O-BSA) immunoglobulin M (IgM) and antifusion protein of ML0405-ML2331 IgG for MB were 97.96% and 89.8%, and these values for PB were 70% and 53.33%. However, the ND-O-BSA enzyme-linked immunosorbent assay (ELISA) had lower specificity, with relatively high false-positive results for TB patients (16.67%) and normal healthy controls (10%). Based on these promising findings, we propose the use of nested PCR of whole-blood samples along with ELISA test for early detection of leprosy cases. PMID:23478578

Characteristics in childhood and adolescence associated with future multiple sclerosis risk in men: cohort study.

PubMed

Gunnarsson, M; Udumyan, R; Bahmanyar, S; Nilsagård, Y; Montgomery, S

2015-07-01

Associations with multiple sclerosis (MS) of living conditions in childhood and characteristics in adolescence including physical fitness, cognitive function and psychological stress resilience were investigated. A cohort of male Swedish residents born 1952-1956 who were included in the Swedish Military Conscription Register was used to create a nested case-control study comprising 628 MS cases and 6187 controls matched on birth year, county of residence and vital status at time of diagnosis. Conscription examination records were linked with other national register data. Conditional logistic regression was used to evaluate associations with MS subsequent to the conscription examination. Men with MS were less likely to be from more crowded households in childhood (>two persons per room) with an adjusted odds ratio of 0.67 (95% confidence interval 0.51-0.86, P = 0.023). They had lower physical working capacity in adolescence with adjusted odds ratio of 0.94 (95% confidence interval 0.89-0.99, P = 0.026). Cognitive function and stress resilience scores displayed no significant differences between cases and controls. Parental occupation in childhood and body mass index in adolescence were not associated with future MS risk. The inverse association of MS risk with higher levels of household crowding may reflect environmental factors such as the pattern of exposure to microorganisms. Lower physical fitness in men at MS risk may indicate a protective effect of exercise or could be due to prodromal disease activity, although there was no association with cognitive function. Poor psychological stress resilience (and thus risk of chronic stress arousal) was not associated with MS. © 2015 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

Bridging the etiologic and prognostic outlooks in individualized assessment of absolute risk of an illness: application in lung cancer.

PubMed

Karp, Igor; Sylvestre, Marie-Pierre; Abrahamowicz, Michal; Leffondré, Karen; Siemiatycki, Jack

2016-11-01

Assessment of individual risk of illness is an important activity in preventive medicine. Development of risk-assessment models has heretofore relied predominantly on studies involving follow-up of cohort-type populations, while case-control studies have generally been considered unfit for this purpose. To present a method for individualized assessment of absolute risk of an illness (as illustrated by lung cancer) based on data from a 'non-nested' case-control study. We used data from a case-control study conducted in Montreal, Canada in 1996-2001. Individuals diagnosed with lung cancer (n = 920) and age- and sex-matched lung-cancer-free subjects (n = 1288) completed questionnaires documenting life-time cigarette-smoking history and occupational, medical, and family history. Unweighted and weighted logistic models were fitted. Model overfitting was assessed using bootstrap-based cross-validation and 'shrinkage.' The discriminating ability was assessed by the c-statistic, and the risk-stratifying performance was assessed by examination of the variability in risk estimates over hypothetical risk-profiles. In the logistic models, the logarithm of incidence-density of lung cancer was expressed as a function of age, sex, cigarette-smoking history, history of respiratory conditions and exposure to occupational carcinogens, and family history of lung cancer. The models entailed a minimal degree of overfitting ('shrinkage' factor: 0.97 for both unweighted and weighted models) and moderately high discriminating ability (c-statistic: 0.82 for the unweighted model and 0.66 for the weighted model). The method's risk-stratifying performance was quite high. The presented method allows for individualized assessment of risk of lung cancer and can be used for development of risk-assessment models for other illnesses.

First trimester maternal uterine artery Doppler examination in HIV-positive women.

PubMed

Savvidou, M D; Samuel, M I; Akolekar, R; Poulton, M; Nicolaides, K H

2011-11-01

The aim of the current study was to assess the effect of maternal HIV infection, treated or untreated, on the degree of placental invasion, as assessed by the pulsatility index of the uterine arteries during a Doppler examination at 11(+0) -13(+6) weeks' gestation. This was a nested case-control study in which a uterine artery Doppler examination was performed in the first trimester in 76 HIV-positive women. Each woman was matched with 30 HIV-negative women. As the pulsatility index of the uterine arteries depends on a number of maternal and fetal characteristics, its values in each case and control were expressed as multiples of the median (MoM) of the unaffected group. Among the 76 HIV-positive women, 33 (43.4%) were on antiretroviral treatment at the time of the Doppler examination, including 14 women (42.4%) on nucleoside reverse transcriptase inhibitors (NRTIs) and a protease inhibitor, 18 women (54.5%) on NRTIs and a nonnucleoside reverse transcriptase inhibitor and one woman (3.1%) on monotherapy. Compared with the HIV-negative women, the HIV-positive women were more likely to be heavier (P<0.01), to be of African origin (P<0.01), to be nonsmokers (P=0.01) and to deliver smaller neonates earlier (P<0.01). The median adjusted pulsatility index of the uterine arteries was not statistically different between the cases and controls [1.07; interquartile range (IQR) 0.85-1.24 MoM vs. 0.99; IQR 0.81-1.20 MoM; P= 0.28] or, in HIV-positive women, between those receiving and not receiving antiretroviral treatment (P=0.12). HIV-positive women with uncomplicated pregnancies have normal placental perfusion in the first trimester of pregnancy. 2011 British HIV Association.

A case-control study to assess the impact of mammographic density on breast cancer risk in women aged 40-49 at intermediate familial risk.

PubMed

Assi, Valentina; Massat, Nathalie J; Thomas, Susan; MacKay, James; Warwick, Jane; Kataoka, Masako; Warsi, Iqbal; Brentnall, Adam; Warren, Ruth; Duffy, Stephen W

2015-05-15

Mammographic density is a strong risk factor for breast cancer, but its potential application in risk management is not clear, partly due to uncertainties about its interaction with other breast cancer risk factors. We aimed to quantify the impact of mammographic density on breast cancer risk in women aged 40-49 at intermediate familial risk of breast cancer (average lifetime risk of 23%), in particular in premenopausal women, and to investigate its relationship with other breast cancer risk factors in this population. We present the results from a case-control study nested with the FH01 cohort study of 6,710 women mostly aged 40-49 at intermediate familial risk of breast cancer. One hundred and three cases of breast cancer were age-matched to one or two controls. Density was measured by semiautomated interactive thresholding. Absolute density, but not percent density, was a significant risk factor for breast cancer in this population after adjusting for area of nondense tissue (OR per 10 cm(2) = 1.07, 95% CI 1.00-1.15, p = 0.04). The effect was stronger in premenopausal women, who made up the majority of the study population. Absolute density remained a significant predictor of breast cancer risk after adjusting for age at menarche, age at first live birth, parity, past or present hormone replacement therapy, and the Tyrer-Cuzick 10-year relative risk estimate of breast cancer. Absolute density can improve breast cancer risk stratification and delineation of high-risk groups alongside the Tyrer-Cuzick 10-year relative risk estimate. © 2014 UICC.

One-carbon metabolite ratios as functional B-vitamin markers and in relation to colorectal cancer risk.

PubMed

Gylling, Björn; Myte, Robin; Ulvik, Arve; Ueland, Per M; Midttun, Øivind; Schneede, Jörn; Hallmans, Göran; Häggström, Jenny; Johansson, Ingegerd; Van Guelpen, Bethany; Palmqvist, Richard

2018-05-22

One-carbon metabolism biomarkers are easily measured in plasma, but analyzing them one at a time in relation to disease does not take into account the interdependence of the many factors involved. The relative dynamics of major one-carbon metabolism branches can be assessed by relating the functional B-vitamin marker total homocysteine (tHcy) to transsulfuration (total cysteine) and methylation (creatinine) outputs. We validated the ratios of tHcy to total cysteine (Hcy:Cys), tHcy to creatinine (Hcy:Cre), and tHcy to cysteine to creatinine (Hcy:Cys:Cre) as functional markers of B-vitamin status. We also calculated the associations of these ratios to colorectal cancer (CRC) risk. Furthermore, the relative contribution of potential confounders to the variance of the ratio-based B-vitamin markers was calculated by linear regression in a nested case-control study of 613 CRC cases and 1190 matched controls. Total B-vitamin status was represented by a summary score comprising Z-standardized plasma concentrations of folate, cobalamin, betaine, pyridoxal 5'-phosphate, and riboflavin. Associations with CRC risk were estimated using conditional logistic regression. We found that the ratio-based B-vitamin markers all outperformed tHcy as markers of total B-vitamin status, in both CRC cases and controls. Additionally, associations with CRC risk were similar for the ratio-based B-vitamin markers and total B-vitamin status (approximately 25% lower risk for high versus low B-vitamin status). In conclusion, ratio-based B-vitamin markers were good predictors of total B-vitamin status and displayed similar associations as total B-vitamin status with CRC risk. Since tHcy and creatinine are routinely clinically analyzed, Hcy:Cre could be easily implemented in clinical practice. This article is protected by copyright. All rights reserved. © 2018 UICC.

Retinal Vascular Changes and Prospective Risk of Disabling Dementia: the Circulatory Risk in Communities Study (CIRCS)

PubMed Central

Jinnouchi, Hiroshige; Kitamura, Akihiko; Yamagishi, Kazumasa; Kiyama, Masahiko; Imano, Hironori; Okada, Takeo; Cui, Renzhe; Umesawa, Mitsumasa; Muraki, Isao; Hayama-Terada, Mina; Kawasaki, Ryo; Sankai, Tomoko; Ohira, Tetsuya

2017-01-01

Aim: To investigate the association of retinal vascular changes with a risk of dementia in longitudinal population-based study. Methods: We performed a nested case-control study of 3,718 persons, aged 40–89 years, enrolled between 1983 and 2004. Retinal vascular changes were observed in 351 cases with disabling dementia (average period before the onset, 11.2 years) and in 702 controls matched for sex, age, and baseline year. Incidence of disabling dementia was defined as individuals who received cares for disabilities including dementia-related symptoms and/or behavioral disturbance. Conditional logistic regression analysis was used to calculate odds ratio (OR) and multivariable adjusted OR (Models 1 and 2) for incidence of disabling dementia according to each retinal vascular change. Regarding confounding variables, Model 1 included overweight status, hypertension, hyperglycemia, dyslipidemia, and smoking status, whereas Model 2 also included incidence of stroke prior to disabling dementia for further analysis. Results: The proportion of cases (controls) with retinal vascular changes was 23.1 (15.7)% for generalized arteriolar narrowing, 7.7 (7.5)% for focal arteriolar narrowing, 15.7 (11.8)% for arteriovenous nicking, 10.5 (9.3)% for increased arteriolar wall reflex, and 11.4 (9.8)% for any other retinopathy. Generalized arteriolar narrowing was associated with an increased risk of disabling dementia: crude OR, 1.66 (95% confidence interval, 1.19–2.31); Model 1: OR, 1.58 (1.12–2.23); Model 2: OR, 1.48 (1.04–2.10). The number of retinal abnormalities was associated in a dose–response manner with the risk. Conclusion: Generalized arteriolar narrowing and total number of retinal abnormalities may be useful markers for identifying persons at higher risks of disabling dementia. PMID:27904027

A population-based study of the drug interaction between proton pump inhibitors and clopidogrel

PubMed Central

Juurlink, David N.; Gomes, Tara; Ko, Dennis T.; Szmitko, Paul E.; Austin, Peter C.; Tu, Jack V.; Henry, David A.; Kopp, Alex; Mamdani, Muhammad M.

2009-01-01

Background Most proton pump inhibitors inhibit the bioactivation of clopidogrel to its active metabolite. The clinical significance of this drug interaction is unknown. Methods We conducted a population-based nested case–control study among patients aged 66 years or older who commenced clopidogrel between Apr. 1, 2002, and Dec. 31, 2007, following hospital discharge after treatment of acute myocardial infarction. The cases in our study were those readmitted with acute myocardial infarction within 90 days after discharge. We performed a secondary analysis considering events within 1 year. Event-free controls (at a ratio of 3:1) were matched to cases on age, percutaneous coronary intervention and a validated risk score. We categorized exposure to proton pump inhibitors before the index date as current (within 30 days), previous (31–90 days) or remote (91–180 days). Results Among 13 636 patients prescribed clopidogrel following acute myocardial infarction, we identified 734 cases readmitted with myocardial infarction and 2057 controls. After extensive multivariable adjustment, current use of proton pump inhibitors was associated with an increased risk of reinfarction (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.03–1.57). We found no association with more distant exposure to proton pump inhibitors or in multiple sensitivity analyses. In a stratified analysis, pantoprazole, which does not inhibit cytochrome P450 2C19, had no association with readmission for myocardial infarction (adjusted OR 1.02, 95% CI 0.70–1.47). Interpretation Among patients receiving clopidogrel following acute myocardial infarction, concomitant therapy with proton pump inhibitors other than pantoprazole was associated with a loss of the beneficial effects of clopidogrel and an increased risk of reinfarction. PMID:19176635

[Investigation of the factors that contribute to the onset of insomnia in hypertensive patients by using a post-marketing surveillance database].

PubMed

Tanabe, Naoto; Fujita, Toshiharu; Fujii, Yosuke; Orii, Takao

2011-01-01

Many factors contribute to the onset of insomnia. However, few studies have identified the factors related to the onset of insomnia in hypertensive patients. We conducted a pharmacoepidemiologic study to examine the incidence of insomnia in hypertensive patients by using a post-marketing surveillance database. The insomnia onset was defined as the time of first prescription of hypnotics. The insomnia incidence rate in hypertensive patients under antihypertensive therapy was 0.77/100 person-years. The median insomnia onset date was 5 weeks. The insomnia type in 50.2% of the patients was difficulty in initiating sleep. We assessed the factors contributing to insomnia by using a nested case-control design. We selected 10 time-matched controls for every case. The hypotensive effect induced by antihypertensive therapy on the case group was lesser than that on the control group (p<0.01). The odds ratios (ORs) were estimated using multivariate conditional logistic regression. The factors contributing to insomnia onset were α blockers (OR, 2.38; 95% confidence interval [CI], 1.14-4.98), β blockers (OR, 1.54; 95% CI, 0.99-2.39), and calcium channel blockers (OR, 0.62; 95% CI, 0.43-0.90) compared with angiotensin-converting enzyme inhibitors; female sex (OR, 1.76; 95% CI, 1.27-2.44); complication of gastric/duodenal disorders (OR, 2.35; 95% CI, 1.14-4.86) or musculoskeletal system/connective tissue disorders (OR, 2.43; 95% CI, 1.23-4.79); and concomitant antihypertensive therapy (OR, 0.44; 95% CI, 0.31-0.63). This study identified the potential factors that may help to predict insomnia onset in hypertensive patients under antihypertensive therapy.

Social support and ovarian cancer incidence - A Swedish prospective population-based study.

PubMed

Idahl, Annika; Hermansson, Andrea; Lalos, Ann

2018-05-01

Low social support is associated with worse prognosis for epithelial ovarian cancer (EOC) patients. However, few studies have explored the relation between low social support and incidence of EOC. The aim of this prospective nested case-control study was to examine whether self-perceived low social support was associated with the incidence of EOC. The Swedish Cancer Registry was used to identify participants in the Västerbotten Intervention Programme (VIP) comprising 58,000 women, who later developed EOC. Each case was matched to four cancer free controls. The VIP uses the Social Support questionnaire, a modified version of the validated questionnaire "The Interview Schedule for Social Interaction" (ISSI) measuring quantitative (AVSI) and qualitative (AVAT) aspects of social support. The risk of EOC in relation to AVSI and AVAT was similar between the 239 cases and the 941 controls after adjustment for educational level, smoking, BMI, Cambridge Physical Activity Index and age (aOR 0.85, 95% CI 0.72-1.01 and aOR 0.54, 95% CI 0.16-1.81). Lagtime was found to have no impact. A decreased risk of serous ovarian cancer was seen in women with fewer persons available for informal socializing (aOR 0.75, 95% CI 0.59-0.95). Adjusted analyses showed non-significant odds ratios below 1.0 in the vast majority of histotypes. A general trend towards a decreased risk of ovarian cancer associated with low AVSI and AVAT was identified. Solely the serous subtype was significantly associated with low scores of AVSI. Prospective pathophysiological and epidemiological studies regarding social support are needed. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Impact of anti-rheumatic treatment on cardiovascular risk in Asian patients with rheumatoid arthritis.

PubMed

Cho, Soo-Kyung; Kim, Dam; Won, Soyoung; Lee, Jiyoung; Park, ByeongJu; Jang, Eun Jin; Bae, Sang-Cheol; Sung, Yoon-Kyoung

2018-02-01

To estimate the incidence of cardiovascular disease (CVD) in Asian patients with rheumatoid arthritis (RA) and to evaluate the impact of anti-rheumatic treatment on the development of CVD. A retrospective cohort of Asian patients with RA was established to identify the incidence rate (IR) of CVD in RA patients. The cohort was generated using the Korean National Healthcare claims database, which contained claims from Jan 2009 to Dec 2013. A total of 137,512 RA patients were identified; individuals with a history of CVD for 6 months or more before the index date were excluded. Nested case-control samples were drawn from the full study population with a case:control ratio of 1:4 (n = 7102 cases; n = 27,018 controls without CVD). A conditional multivariate regression model was used to evaluate the impact of anti-rheumatic treatment on the development of CVD in RA patients after matching for age, sex, RA index date, comorbidities, and drug use (e.g., antiplatelet agents and cholesterol-lowering agents). The IR for development of overall CVD in RA patients was 182.1 (95% CI: 178.4-185.9) per 10,000 person-years. In models adjusted for other CVD risk factors, disease-modifying anti-rheumatic drugs (DMARDs) (OR = 0.79) were protective against CVD, and biologic DMARDs were not significantly associated with CVD risk (OR = 0.85). Corticosteroids (OR = 1.26) and NSAIDs (nonselective NSAIDs: OR = 1.32, Cox-2 inhibitors: OR = 1.31) were risk factors for CVD in RA patients. The use of DMARDs is protective against CVD, while corticosteroids and NSAIDs increased the risk of CVD in RA patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Early life course risk factors for childhood obesity: the IDEFICS case-control study.

PubMed

Bammann, Karin; Peplies, Jenny; De Henauw, Stefaan; Hunsberger, Monica; Molnar, Denes; Moreno, Luis A; Tornaritis, Michael; Veidebaum, Toomas; Ahrens, Wolfgang; Siani, Alfonso

2014-01-01

The early life course is assumed to be a critical phase for childhood obesity; however the significance of single factors and their interplay is not well studied in childhood populations. The investigation of pre-, peri- and postpartum risk factors on the risk of obesity at age 2 to 9. A case-control study with 1,024 1:1-matched case-control pairs was nested in the baseline survey (09/2007-05/2008) of the IDEFICS study, a population-based intervention study on childhood obesity carried out in 8 European countries in pre- and primary school settings. Conditional logistic regression was used for identification of risk factors. For many of the investigated risk factors, we found a raw effect in our study. In multivariate models, we could establish an effect for gestational weight gain (adjusted OR = 1.02; 95%CI 1.00-1.04), smoking during pregnancy (adjusted OR = 1.48; 95%CI 1.08-2.01), Caesarian section (adjusted OR = 1.38; 95%CI 1.10-1.74), and breastfeeding 4 to 11 months (adjusted OR = 0.77; 95%CI 0.62-0.96). Birth weight was related to lean mass rather than to fat mass, the effect of smoking was found only in boys, but not in girls. After additional adjustment for parental BMI and parental educational status, only gestational weight gain remained statistically significant. Both, maternal as well as paternal BMI were the strongest risk factors in our study, and they confounded several of the investigated associations. Key risk factors of childhood obesity in our study are parental BMI and gestational weight gain; consequently prevention approaches should target not only children but also adults. The monitoring of gestational weight seems to be of particular importance for early prevention of childhood obesity.

Antipsychotic treatment and the risk of hip fracture in subjects with schizophrenia: a 10-year population-based case-control study.

PubMed

Wu, Chi-Shin; Chang, Chia-Ming; Tsai, Yu-Ting; Huang, Ya-Wen; Tsai, Hui-Ju

2015-09-01

To investigate the association between antipsychotic treatment and risk of hip fracture in subjects with schizophrenia. Among patients with schizophrenia (ICD-9-CM code 295), 605 cases with hip fracture and 2,828 matched controls were identified from 2002 to 2011 using the National Health Insurance Research Database in Taiwan. The authors conducted a nested case-control study to investigate the association between antipsychotic treatment and risk of hip fracture in subjects with schizophrenia. The modifiable effects of age and gender were evaluated by stratified analysis. In addition, the effects of antipsychotic use, antipsychotic classes, and receptor-binding profiles of antipsychotics, individually, on hip fracture were estimated, and potential confounding factors were adjusted in subsequent analysis. Conditional logistic regressions were applied to determine the effect of antipsychotic treatment on hip fracture. Current antipsychotic use was associated with an increased risk for hip fracture (adjusted odds ratio [AOR] = 1.61; 95% CI, 1.24-2.10). Among current users, new users had a higher risk of hip fracture (AOR = 4.28; 95% CI, 1.76-10.36) than past users (AOR = 1.11; 95% CI, 0.79-1.56). In addition, a significant increased risk of hip fracture was noted in schizophrenia subjects with first-generation antipsychotic use (AOR = 1.59; 95%CI, 1.15-2.20) but not in those with second-generation antipsychotic use (AOR = 1.16; 95% CI, 0.91-1.48). These results extend previous findings and demonstrate an increased risk of hip fracture associated with antipsychotic use in schizophrenia subjects. Further investigation is needed to dissect the underlying mechanisms related to the effect of antipsychotic use on hip fracture in subjects at risk. © Copyright 2015 Physicians Postgraduate Press, Inc.

From neurons to nests: nest-building behaviour as a model in behavioural and comparative neuroscience.

PubMed

Hall, Zachary J; Meddle, Simone L; Healy, Susan D

Despite centuries of observing the nest building of most extant bird species, we know surprisingly little about how birds build nests and, specifically, how the avian brain controls nest building. Here, we argue that nest building in birds may be a useful model behaviour in which to study how the brain controls behaviour. Specifically, we argue that nest building as a behavioural model provides a unique opportunity to study not only the mechanisms through which the brain controls behaviour within individuals of a single species but also how evolution may have shaped the brain to produce interspecific variation in nest-building behaviour. In this review, we outline the questions in both behavioural and comparative neuroscience that nest building could be used to address, summarize recent findings regarding the neurobiology of nest building in lab-reared zebra finches and across species building different nest structures, and suggest some future directions for the neurobiology of nest building.

Genome-Wide Associations and Functional Genomic Studies of Musculoskeletal Adverse Events in Women Receiving Aromatase Inhibitors

PubMed Central

Ingle, James N.; Schaid, Daniel J.; Goss, Paul E.; Liu, Mohan; Mushiroda, Taisei; Chapman, Judy-Anne W.; Kubo, Michiaki; Jenkins, Gregory D.; Batzler, Anthony; Shepherd, Lois; Pater, Joseph; Wang, Liewei; Ellis, Matthew J.; Stearns, Vered; Rohrer, Daniel C.; Goetz, Matthew P.; Pritchard, Kathleen I.; Flockhart, David A.; Nakamura, Yusuke; Weinshilboum, Richard M.

2010-01-01

Purpose We performed a case-control genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with musculoskeletal adverse events (MS-AEs) in women treated with aromatase inhibitors (AIs) for early breast cancer. Patients and Methods A nested case-control design was used to select patients enrolled onto the MA.27 phase III trial comparing anastrozole with exemestane. Cases were matched to two controls and were defined as patients with grade 3 or 4 MS-AEs (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0) or those who discontinued treatment for any grade of MS-AE within the first 2 years. Genotyping was performed with the Illumina Human610-Quad BeadChip. Results The GWAS included 293 cases and 585 controls. A total of 551,358 SNPs were analyzed, followed by imputation and fine mapping of a region of interest on chromosome 14. Four SNPs on chromosome 14 had the lowest P values (2.23E-06 to 6.67E-07). T-cell leukemia 1A (TCL1A) was the gene closest (926-7000 bp) to the four SNPs. Functional genomic studies revealed that one of these SNPs (rs11849538) created an estrogen response element and that TCL1A expression was estrogen dependent, was associated with the variant SNP genotypes in estradiol-treated lymphoblastoid cells transfected with estrogen receptor alpha and was directly related to interleukin 17 receptor A (IL17RA) expression. Conclusion This GWAS identified SNPs associated with MS-AEs in women treated with AIs and with a gene (TCL1A) which, in turn, was related to a cytokine (IL17). These findings provide a focus for further research to identify patients at risk for MS-AEs and to explore the mechanisms for these adverse events. PMID:20876420

Dentine sensitivity risk factors: A case-control study.

PubMed

Mafla, Ana Cristina; Lopez-Moncayo, Luis Fernando

2016-01-01

To identify the clinical and psychological risk factors associated with dentine hypersensitivity (DH) in order to provide an early diagnosis and preventive therapy. A nested case-control study was design between 2011 and 2012. A total of 61 DH cases and 122 controls participated in this investigation. Cases and controls were matched for sex, group of age and socioeconomic status in a ratio of 1:2. DH to different stimuli such as cold, heat, acid, and sweet was asked in patient interviews, and dental examinations were used to detect DH. Clinical and psychological risk factors such as dental hygiene, periodontal disease, acid diet, alcohol consumption, psychological stress, and psychopathological symptoms were inquired. Psychological stress was measured through the PSS-10 and psychopathological symptoms were evaluated by SCL-90-R in Spanish. Descriptive and univariate binary logistic regression analysis were performed to estimate the association between clinical and psychological risk factors and the presence of DH. Toothpaste abrasivity (odds ratio [OR] 1.881, 95% confidence interval [CI] 1.010-3.502, P = 0.045), gingival recession (OR 2.196, 95% CI 1.020-4.728, P = 0.041), and periodontal therapy (OR 5.357, 95% CI 2.051-13.993, P < 0.001) were associated with DH. Subjects with perceived stress (OR 1.211, 95%, CI 0.518-2.833, P = 0.658), obsessive-compulsive (OR 1.266, 95%, CI 0.494-3.240, P = 0.623) and hostility (OR 1.235, 95%, CI 0.507-3.007, P = 0.642) symptoms had a clinical greater odd of DH. Oral hygiene products and periodontal conditions are important risk factors for DH. Individuals with perceived stress, obsessive-compulsive, and hostility symptoms may increase a clinical risk for this entity. Targeting to dental counseling focused on oral hygiene products, periodontal therapy and a psychological evaluation may be promising in DH prevention.

Low Vitamin D Status and Suicide: A Case-Control Study of Active Duty Military Service Members

PubMed Central

Umhau, John C.; George, David T.; Heaney, Robert P.; Lewis, Michael D.; Ursano, Robert J.; Heilig, Markus

2013-01-01

Objective Considering that epidemiological studies show that suicide rates in many countries are highest in the spring when vitamin D status is lowest, and that low vitamin D status can affect brain function, we sought to evaluate if a low level of 25-hydroxyvitamin D [25(OH)D] could be a predisposing factor for suicide. Method We conducted a prospective, nested, case-control study using serum samples stored in the Department of Defense Serum Repository. Participants were previously deployed active duty US military personnel (2002–2008) who had a recent archived serum sample available for analysis. Vitamin D status was estimated by measuring 25(OH) D levels in serum samples drawn within 24 months of the suicide. Each verified suicide case (n = 495) was matched to a control (n = 495) by rank, age and sex. We calculated odds ratio of suicide associated with categorical levels (octiles) of 25(OH) D, adjusted by season of serum collection. Findings More than 30% of all subjects had 25(OH)D values below 20 ng/mL. Although mean serum 25(OH)D concentrations did not differ between suicide cases and controls, risk estimates indicated that subjects in the lowest octile of season-adjusted 25(OH)D (<15.5 ng/mL) had the highest risk of suicide, with subjects in the subsequent higher octiles showing approximately the same level of decreased risk (combined odds ratio compared to lowest octile  = 0.49; 95% C.I.: 0.315–0.768). Conclusions Low vitamin D status is common in active duty service members. The lowest 25(OH)D levels are associated with an increased risk for suicide. Future studies could determine if additional sunlight exposure and vitamin D supplementation might reduce suicide by increasing 25(OH) D levels. PMID:23308099

Occupational solvent exposure and adult chronic lymphocytic leukemia: No risk in a population-based case-control study in four Nordic countries.

PubMed

Talibov, Madar; Auvinen, Anssi; Weiderpass, Elisabete; Hansen, Johnni; Martinsen, Jan-Ivar; Kjaerheim, Kristina; Tryggvadottir, Laufey; Pukkala, Eero

2017-09-15

The aim of this study was to assess the effect of occupational solvent exposure on the risk of adult chronic lymphocytic leukemia (CLL). The current case-control study was nested in the Nordic Occupational Cancer Study (NOCCA) cohort. 20,615 CLL cases diagnosed in 1961-2005 in Finland, Iceland, Norway, and Sweden, and 103,075 population-based controls matched by year of birth, sex, and country were included. Occupational histories for cases and controls were obtained from census records in 1960, 1970, 1980/1981, and 1990. Exposure to selected solvents was estimated by using the NOCCA job-exposure matrix (NOCCA-JEM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by using conditional logistic regression models. Overall, nonsignificant CLL risk elevations were observed for methylene chloride, perchloroethylene, and 1,1,1-trichloroethane. Compared to unexposed, significantly increased risks were observed for cumulative perchloroethylene exposure ≤13.3 ppm-years (OR = 1.85, 95% CI 1.16-2.96) and average life-time perchloroethylene exposure ≤2.5 ppm (1.61, 95% CI 1.01-2.56) among women, and cumulative methylene chloride exposure ≤12.5 ppm-years (OR = 1.19, 95% CI 1.01-1.41) and 12.5-74.8 ppm-years (OR = 1.23, 95% CI 1.01-1.51) among men in an analysis with 5 years lag-time, though without dose-response pattern. Decreased CLL risk was observed for aliphatic and alicyclic hydrocarbon solvents and toluene. This study did not support associations for solvent exposure and CLL. Observed weak associations for methylene chloride, perchloroethylene, 1,1,1-trichloroethane exposures, aliphatic and alicyclic hydrocarbons and toluene were not consistent across sexes, and showed no gradient with amount of exposure. © 2017 UICC.

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.

Risk and protective factors for meningococcal disease in adolescents: matched cohort study

PubMed Central

Tully, Joanna; Viner, Russell M; Coen, Pietro G; Stuart, James M; Zambon, Maria; Peckham, Catherine; Booth, Clare; Klein, Nigel; Kaczmarski, Ed; Booy, Robert

2006-01-01

Objective To examine biological and social risk factors for meningococcal disease in adolescents. Design Prospective, population based, matched cohort study with controls matched for age and sex in 1:1 matching. Controls were sought from the general practitioner. Setting Six contiguous regions of England, which represent some 65% of the country's population. Participants 15-19 year olds with meningococcal disease recruited at hospital admission in six regions (representing 65% of the population of England) from January 1999 to June 2000, and their matched controls. Methods Blood samples and pernasal and throat swabs were taken from case patients at admission to hospital and from cases and matched controls at interview. Data on potential risk factors were gathered by confidential interview. Data were analysed by using univariate and multivariate conditional logistic regression. Results 144 case control pairs were recruited (74 male (51%); median age 17.6). 114 cases (79%) were confirmed microbiologically. Significant independent risk factors for meningococcal disease were history of preceding illness (matched odds ratio 2.9, 95% confidence interval 1.4 to 5.9), intimate kissing with multiple partners (3.7, 1.7 to 8.1), being a university student (3.4, 1.2 to 10) and preterm birth (3.7, 1.0 to 13.5). Religious observance (0.09, 0.02 to 0.6) and meningococcal vaccination (0.12, 0.04 to 0.4) were associated with protection. Conclusions Activities and events increasing risk for meningococcal disease in adolescence are different from in childhood. Students are at higher risk. Altering personal behaviours could moderate the risk. However, the development of further effective meningococcal vaccines remains a key public health priority. PMID:16473859

Field investigation of influenza vaccine effectiveness on morbidity.

PubMed

Carrat, F; Tachet, A; Rouzioux, C; Housset, B; Valleron, A J

1998-01-01

Our objective was to evaluate influenza vaccine effectiveness during an influenza epidemic by means of a matched case-control study. The study was performed by 35 general practitioners who collected specimens for influenza virus testing from 610 patients who consulted for infectious syndrome: 168 (28%) were influenza-positive. Two designs were used for selecting controls to take into account the high incidence-rate of influenza-like illness and the various possible protective effects of the vaccine. A first disease-free control matched for age and sex was selected during the same week as the case. A second control matched for age and sex was selected at the end of the epidemic period, irrespective of disease history during the epidemic period. Upper and lower bounds of vaccine effectiveness can be derived from these case-control designs. After adjustment for chronic conditions and exposure to an index case, analysis of the matched-pairs whose case was influenza-positive showed, with the first group of controls, an influenza vaccine effectiveness of 68% (95% CI, 10% to 88%) and, in the second group, 53% (95% CI, -19% to 82%). Among the pairs whose case was negative for influenza, vaccine effectiveness was, respectively, 31% (95% CI, -17% to 59%) and 12% (95% CI, -47% to 47%). Vaccine effectiveness was highest for the H3N2 subtype whose vaccine strain was identical to that of the wild-type strain. The results suggest that influenza vaccine is effective in the field in preventing influenza morbidity.

Argyrophilic grain disease as a neurodegenerative substrate in late-onset schizophrenia and delusional disorders.

PubMed

Nagao, Shigeto; Yokota, Osamu; Ikeda, Chikako; Takeda, Naoya; Ishizu, Hideki; Kuroda, Shigetoshi; Sudo, Koichiro; Terada, Seishi; Murayama, Shigeo; Uchitomi, Yosuke

2014-06-01

To study the relationship between neurodegenerative diseases including argyrophilic grain disease (AGD) and late-onset schizophrenia and delusional disorders (LOSD; onset ≥40 years of age), we pathologically examined 23 patients with LOSD, 71 age-matched normal controls, and 22 psychiatric disease controls (11 depression, six personality disorder, two bipolar disorders, and three neurotic disorders cases). In all LOSD cases (compared to age-matched normal controls), the frequencies of Lewy body disease (LBD), AGD, and corticobasal degeneration (CBD) were 26.1 % (11.3 %), 21.7 % (8.5 %), and 4.3 % (0.0 %), respectively. There was no case of pure Alzheimer's disease (AD). The total frequency of LBD, AGD, and CBD was significantly higher in LOSD cases than in normal controls. Argyrophilic grains were significantly more severe in LOSD than in controls, but were almost completely restricted to the limbic system and adjacent temporal cortex. In LOSD patients whose onset occurred at ≥65 years of age (versus age-matched normal controls), the frequencies of LBD and AGD were 36.4 % (19.4 %) and 36.4 % (8.3 %), respectively, and AGD was significantly more frequent in LOSD patients than in normal controls. In LOSD patients whose onset occurred at <65 years of age, the frequencies of LBD, AGD, and CBD were 16.7, 8.3, and 8.3 %, comparable to those of age-matched normal controls (10.2, 5.1, and 0.0 %). In all psychiatric cases, delusion was significantly more frequent in AGD cases than in cases bearing minimal AD pathology alone. Given these findings, LOSD patients may have heterogeneous pathological backgrounds, and AGD may be associated with the occurrence of LOSD especially after 65 years of age.

Clinical factors associated with readmission for postpartum hypertension in women with pregnancy-related hypertension: a nested case control study.

PubMed

Hirshberg, A; Levine, L D; Srinivas, S K

2016-05-01

To evaluate the association between mode of delivery and length of labor on readmission for postpartum hypertension in women with pregnancy-related hypertension. Nested case control study within a cohort of 99 women with pregnancy-related hypertension who delivered at our institution between 2005 and 2009. Data were abstracted for clinical and labor information. Mode of delivery and length of labor were compared between women with previously diagnosed pregnancy-related hypertension readmitted within 4 weeks post partum (25 cases) and those not readmitted (74 controls). Categorical and continuous variables were compared using χ(2) and T-tests, respectively. Multivariable logistic regression controlled for confounders. Hypertension readmission was not associated with mode of delivery (cases: 10(40%) spontaneous vaginal delivery, 15(60%) cesarean delivery; controls: 38(51%) spontaneous vaginal delivery, 36(49%) cesarean delivery, P=0.33). Length of labor appeared longer in cases, with a trend toward significance (median: 15.5 [7,28] h vs 10.75 [5.8,15.9] h, P=0.12) and was significantly associated with readmission after controlling for delivery mode, induction and parity (adjusted odds ratio=1.06 [1 to 1.12], P=0.048). Readmitted patients were less likely to have initially been started on antihypertensive medications after controlling for age, race and chronic hypertension (adjusted odds ratio=0.23 [0.06 to 0.88], P=0.03). Postpartum readmission for hypertension in women with known pregnancy-related hypertension is not associated with mode of delivery, appears increased in those with longer length of labor and decreased in those initially started on antihypertensive medications. This provides targets for future research to continue to improve transitions of care and reduce preventable readmissions.

Clinical factors associated with readmission for postpartum hypertension in women with pregnancy-related hypertension: a nested case control study

PubMed Central

Hirshberg, A; Levine, LD; Srinivas, SK

2017-01-01

Objective To evaluate the association between mode of delivery and length of labor on readmission for postpartum hypertension in women with pregnancy-related hypertension. Study Design Nested case control study within a cohort of 99 women with pregnancy-related hypertension who delivered at our institution between 2005 and 2009. Data were abstracted for clinical and labor information. Mode of delivery and length of labor were compared between women with previously diagnosed pregnancy-related hypertension readmitted within 4 weeks post partum (25 cases) and those not readmitted (74 controls). Categorical and continuous variables were compared using χ2 and T-tests, respectively. Multivariable logistic regression controlled for confounders. Result Hypertension readmission was not associated with mode of delivery (cases: 10(40%) spontaneous vaginal delivery, 15(60%) cesarean delivery; controls: 38(51%) spontaneous vaginal delivery, 36(49%) cesarean delivery, P=0.33). Length of labor appeared longer in cases, with a trend toward significance (median: 15.5 [7,28] h vs 10.75 [5.8,15.9] h, P=0.12) and was significantly associated with readmission after controlling for delivery mode, induction and parity (adjusted odds ratio = 1.06 [1 to 1.12], P = 0.048). Readmitted patients were less likely to have initially been started on antihypertensive medications after controlling for age, race and chronic hypertension (adjusted odds ratio = 0.23 [0.06 to 0.88], P=0.03). Conclusion Postpartum readmission for hypertension in women with known pregnancy-related hypertension is not associated with mode of delivery, appears increased in those with longer length of labor and decreased in those initially started on antihypertensive medications. This provides targets for future research to continue to improve transitions of care and reduce preventable readmissions. PMID:26765549

The effects of particulate air pollution on daily deaths: a multi-city case crossover analysis

PubMed Central

Schwartz, J

2004-01-01

Background: Numerous studies have reported that day-to-day changes in particulate air pollution are associated with day-to-day changes in deaths. Recently, several reports have indicated that the software used to control for season and weather in some of these studies had deficiencies. Aims: To investigate the use of the case-crossover design as an alternative. Methods: This approach compares the exposure of each case to their exposure on a nearby day, when they did not die. Hence it controls for seasonal patterns and for all slowly varying covariates (age, smoking, etc) by matching rather than complex modelling. A key feature is that temperature can also be controlled by matching. This approach was applied to a study of 14 US cities. Weather and day of the week were controlled for in the regression. Results: A 10 µg/m3 increase in PM10 was associated with a 0.36% increase in daily deaths from internal causes (95% CI 0.22% to 0.50%). Results were little changed if, instead of symmetrical sampling of control days the time stratified method was applied, when control days were matched on temperature, or when more lags of winter time temperatures were used. Similar results were found using a Poisson regression, but the case-crossover method has the advantage of simplicity in modelling, and of combining matched strata across multiple locations in a single stage analysis. Conclusions: Despite the considerable differences in analytical design, the previously reported associations of particles with mortality persisted in this study. The association appeared quite linear. Case-crossover designs represent an attractive method to control for season and weather by matching. PMID:15550600

Associations between ambient air pollution and daily mortality in a cohort of congestive heart failure: Case-crossover and nested case-control analyses using a distributed lag nonlinear model.

PubMed

Buteau, Stephane; Goldberg, Mark S; Burnett, Richard T; Gasparrini, Antonio; Valois, Marie-France; Brophy, James M; Crouse, Dan L; Hatzopoulou, Marianne

2018-04-01

Persons with congestive heart failure may be at higher risk of the acute effects related to daily fluctuations in ambient air pollution. To meet some of the limitations of previous studies using grouped-analysis, we developed a cohort study of persons with congestive heart failure to estimate whether daily non-accidental mortality were associated with spatially-resolved, daily exposures to ambient nitrogen dioxide (NO 2 ) and ozone (O 3 ), and whether these associations were modified according to a series of indicators potentially reflecting complications or worsening of health. We constructed the cohort from the linkage of administrative health databases. Daily exposure was assigned from different methods we developed previously to predict spatially-resolved, time-dependent concentrations of ambient NO 2 (all year) and O 3 (warm season) at participants' residences. We performed two distinct types of analyses: a case-crossover that contrasts the same person at different times, and a nested case-control that contrasts different persons at similar times. We modelled the effects of air pollution and weather (case-crossover only) on mortality using distributed lag nonlinear models over lags 0 to 3 days. We developed from administrative health data a series of indicators that may reflect the underlying construct of "declining health", and used interactions between these indicators and the cross-basis function for air pollutant to assess potential effect modification. The magnitude of the cumulative as well as the lag-specific estimates of association differed in many instances according to the metric of exposure. Using the back-extrapolation method, which is our preferred exposure model, we found for the case-crossover design a cumulative mean percentage changes (MPC) in daily mortality per interquartile increment in NO 2 (8.8 ppb) of 3.0% (95% CI: -0.9, 6.9%) and for O 3 (16.5 ppb) 3.5% (95% CI: -4.5, 12.1). For O 3 there was strong confounding by weather (unadjusted MPC = 7.1%; 95% CI: 1.7, 12.7%). For the nested case-control approach the cumulative MPC for NO 2 in daily mortality was 2.9% (95% CI: -0.9, 6.9%) and for O 3 7.3% (95% CI: 3.0, 11.9%). We found evidence of effect modification between daily mortality and cumulative NO 2 and O 3 according to the prescribed dose of furosemide in the nested case-control analysis, but not in the case-crossover analysis. Mortality in congestive heart failure was associated with exposure to daily ambient NO 2 and O 3 predicted from a back-extrapolation method using a land use regression model from dense sampling surveys. The methods used to assess exposure can have considerable influence on the estimated acute health effects of the two air pollutants. Copyright © 2018 Elsevier Ltd. All rights reserved.

A nested case-control study of prenatal vanadium exposure and low birthweight.

PubMed

Jiang, Minmin; Li, Yuanyuan; Zhang, Bin; Zhou, Aifen; Zheng, Tongzhang; Qian, Zhengmin; Du, Xiaofu; Zhou, Yanqiu; Pan, Xinyun; Hu, Jie; Wu, Chuansha; Peng, Yang; Liu, Wenyu; Zhang, Chuncao; Xia, Wei; Xu, Shunqing

2016-09-01

Is prenatal vanadium exposure associated with adverse birth outcomes? The odds of low birthweight (LBW) are increased 2.23-fold in mothers with a urinary vanadium of ≥2.91 μg/g creatinine compared with that in mothers with a urinary vanadium of ≤1.42 μg/g creatinine. Human exposure to vanadium occurs through intake of food, water and polluted air. Vanadium has been suggested to have fetotoxicity and developmental toxicity in animal studies, and epidemiological studies have reported an association between a decrease in birthweight and vanadium exposure estimated from particulate matter. A nested case-control study involving 816 study participants (204 LBW cases and 612 matched controls) was conducted with data from the prospective Healthy Baby Cohort between 2012 and 2014 in the province of Hubei, China. Vanadium concentrations in 816 maternal urine samples collected before delivery [the median gestational age was 39 weeks (range 27-42 weeks)] were measured by inductively coupled plasma mass spectrometry. Information on the infants' birth outcomes was obtained from medical records. Conditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). The median urinary vanadium concentration of the cases was much higher than that of the controls (3.04 μg/g creatinine versus 1.93 μg/g creatinine). The results revealed a significant positive trend between the odds of LBW and level of maternal urinary vanadium [relative to the lowest tertile; adjusted OR = 1.69 (95% CI: 0.92, 3.10) for the medium tertile; adjusted OR = 2.23 (95% CI: 1.23, 4.05) for the highest tertile; P-trend = 0.02]. Additionally, the association was not modified by maternal age (P for heterogeneity = 0.70) or infant gender (P for heterogeneity = 0.21). The maternal urine sample was collected before labor, and the maternal urinary vanadium levels measured at one point in time may not accurately reflect the vanadium burden during the entire pregnancy. The results of this study can enrich the biological monitoring data on urinary vanadium in pregnant women; and may be evidence that vanadium may affect fetal development. This work was supported by the National Natural Science Foundation of China (21437002, 81372959 and 81402649), the R&D Special Fund for Public Welfare Industry (Environment) (201309048) and the Fundamental Research Funds for the Central Universities, HUST (2016YXZD043). The authors have no conflicts of interest to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Review of the literature on benzene exposure and leukemia subtypes.

PubMed

Schnatter, A Robert; Rosamilia, Kim; Wojcik, Nancy C

2005-05-30

The epidemiologic literature on benzene exposure and leukemia in the MEDLINE and TOXNET databases was examined through October 2004 using the keywords "benzene", "leukemia" and "adverse health effects". This search was complemented by reviewing the reference lists from extant literature reviews and criteria documents on benzene. Published studies were characterized according to the type of industry studied and design, exposure assessment, disease classification, and control for confounding variables. Study design consisted of either cohort studies or case-control studies, which were further categorized into population-based and nested case-control studies. Disease classification considered the source of diagnostic information, whether there was clinical confirmation from medical records or histopathological, morphological and/or cytogenetic reviews, and as to whether the International Classification of Diseases (ICD) or the French-American-British (FAB) schemes were used (no studies used the Revised European-American Lymphoma (REAL) classification scheme). Nine cohort and 13 case-control studies met inclusion criteria for this review. High and significant acute myeloid leukemia risks with positive dose response relationships were identified across study designs, particularly in the "well-conducted" cohort studies and especially in more highly exposed workers in rubber, shoe, and paint industries. Risks for chronic lymphocytic leukemia (CLL) tended to show elevations in nested case-control studies, with possible dose response relationships in at least two of the three studies. However, cohort studies on CLL show no such risks. Data for chronic myeloid leukemia and acute lymphocytic leukemia are sparse and inconclusive.

Use of antibiotics during pregnancy and risk of spontaneous abortion.

PubMed

Muanda, Flory T; Sheehy, Odile; Bérard, Anick

2017-05-01

Although antibiotics are widely used during pregnancy, evidence regarding their fetal safety remains limited. Our aim was to quantify the association between antibiotic exposure during pregnancy and risk of spontaneous abortion. We conducted a nested case-control study within the Quebec Pregnancy Cohort (1998-2009). We excluded planned abortions and pregnancies exposed to fetotoxic drugs. Spontaneous abortion was defined as having a diagnosis or procedure related to spontaneous abortion before the 20th week of pregnancy. The index date was defined as the calendar date of the spontaneous abortion. Ten controls per case were randomly selected and matched by gestational age and year of pregnancy. Use of antibiotics was defined by filled prescriptions between the first day of gestation and the index date and was compared with (a) non-exposure and (b) exposure to penicillins or cephalosporins. We studied type of antibiotics separately using the same comparator groups. After adjustment for potential confounders, use of azithromycin (adjusted odds ratio [OR] 1.65, 95% confidence interval [CI] 1.34-2.02; 110 exposed cases), clarithromycin (adjusted OR 2.35, 95% CI 1.90-2.91; 111 exposed cases), metronidazole (adjusted OR 1.70, 95% CI 1.27-2.26; 53 exposed cases), sulfonamides (adjusted OR 2.01, 95% CI 1.36-2.97; 30 exposed cases), tetracyclines (adjusted OR 2.59, 95% CI 1.97-3.41; 67 exposed cases) and quinolones (adjusted OR 2.72, 95% CI 2.27-3.27; 160 exposed cases) was associated with an increased risk of spontaneous abortion. Similar results were found when we used penicillins or cephalosporins as the comparator group. After adjustment for potential confounders, use of macro-lides (excluding erythromycin), quinolones, tetracyclines, sulfonamides and metronidazole during early pregnancy was associated with an increased risk of spontaneous abortion. Our findings may be of use to policy-makers to update guidelines for the treatment of infections during pregnancy. © 2017 Canadian Medical Association or its licensors.

Robotic Single-Site and Conventional Laparoscopic Surgery in Gynecology: Clinical Outcomes and Cost Analysis of a Matched Case-Control Study.

PubMed

El Hachem, Lena; Andikyan, Vaagn; Mathews, Shyama; Friedman, Kathryn; Poeran, Jashvant; Shieh, Kenneth; Geoghegan, Michael; Gretz, Herbert F

2016-01-01

To assess the clinical outcomes and costs associated with robotic single-site (RSS) surgery compared with those of conventional laparoscopy (CL) in gynecology. Retrospective case-control study (Canadian Task Force classification II-2). University-affiliated community hospital. Female patients undergoing RSS or CL gynecologic procedures. Comparison of consecutive RSS gynecologic procedures (cases) undertaken between October 2013 and March 2014 with matched CL procedures (controls) completed during the same time period by the same surgeon. Patient demographic data, operative data, and hospital financial data were abstracted from the electronic charts and financial systems. An incremental cost analysis based on the use of disposable equipment was performed. Total hospital charges were determined for matched RSS cases vs CL cases. RSS surgery was completed in 25 out of 33 attempts; 3 cases were aborted before docking, and 5 were converted to a multisite surgery. There were no intraoperative complications or conversions to laparotomy. The completed cases included 11 adnexal cases and 14 hysterectomies, 3 of which included pelvic lymph node dissection. Compared with the CL group, total operative times were higher in the RSS group; however, there were no significant between-group differences in estimated blood loss, length of hospital stay, or complication rates. Disposable equipment cost per case, direct costs, and total hospital charges were evaluated. RSS was associated with an increased disposable cost per case of $248 to $378, depending on the method used for vaginal cuff closure. The average total hospital charges for matched outpatient adnexal surgery were $15,450 for the CL controls and $18,585 for the RSS cases (p < .001), and the average total hospital charges for matched outpatient benign hysterectomy were $14,623 for the CL controls and $21,412 for the RSS cases (p < .001). Although RSS surgery and CL have comparable clinical outcomes in selected patients, RSS surgery remains associated with increased incremental disposable cost per case and total hospital charges. Careful case selection and judicious use of equipment are necessary to maximize cost-effectiveness in RSS gynecologic surgery. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Laryngospasm during emergency department ketamine sedation: a case-control study.

PubMed

Green, Steven M; Roback, Mark G; Krauss, Baruch

2010-11-01

The objective of this study was to assess predictors of emergency department (ED) ketamine-associated laryngospasm using case-control techniques. We performed a matched case-control analysis of a sample of 8282 ED ketamine sedations (including 22 occurrences of laryngospasm) assembled from 32 prior published series. We sequentially studied the association of each of 7 clinical variables with laryngospasm by assigning 4 controls to each case while matching for the remaining 6 variables. We then used univariate statistics and conditional logistic regression to analyze the matched sets. We found no statistical association of age, dose, oropharyngeal procedure, underlying physical illness, route, or coadministered anticholinergics with laryngospasm. Coadministered benzodiazepines showed a borderline association in the multivariate but not univariate analysis that was considered anomalous. This case-control analysis of the largest available sample of ED ketamine-associated laryngospasm did not demonstrate evidence of association with age, dose, or other clinical factors. Such laryngospasm seems to be idiosyncratic, and accordingly, clinicians administering ketamine must be prepared for its rapid identification and management. Given no evidence that they decrease the risk of laryngospasm, coadministered anticholinergics seem unnecessary.

Egg-laying substrate selection for optimal camouflage by quail.

PubMed

Lovell, P George; Ruxton, Graeme D; Langridge, Keri V; Spencer, Karen A

2013-02-04

Camouflage is conferred by background matching and disruption, which are both affected by microhabitat. However, microhabitat selection that enhances camouflage has only been demonstrated in species with discrete phenotypic morphs. For most animals, phenotypic variation is continuous; here we explore whether such individuals can select microhabitats to best exploit camouflage. We use substrate selection in a ground-nesting bird (Japanese quail, Coturnix japonica). For such species, threat from visual predators is high and egg appearance shows strong between-female variation. In quail, variation in appearance is particularly obvious in the amount of dark maculation on the light-colored shell. When given a choice, birds consistently selected laying substrates that made visual detection of their egg outline most challenging. However, the strategy for maximizing camouflage varied with the degree of egg maculation. Females laying heavily maculated eggs selected the substrate that more closely matched egg maculation color properties, leading to camouflage through disruptive coloration. For lightly maculated eggs, females chose a substrate that best matched their egg background coloration, suggesting background matching. Our results show that quail "know" their individual egg patterning and seek out a nest position that provides most effective camouflage for their individual phenotype. Copyright © 2013 Elsevier Ltd. All rights reserved.

Active commuting reduces the risk of wrist fractures in middle-aged women-the UFO study.

PubMed

Englund, U; Nordström, P; Nilsson, J; Hallmans, G; Svensson, O; Bergström, U; Pettersson-Kymmer, U

2013-02-01

Middle-aged women with active commuting had significantly lower risk for wrist fracture than women commuting by car/bus. Our purpose was to investigate whether a physically active lifestyle in middle-aged women was associated with a reduced risk of later sustaining a low-trauma wrist fracture. The Umeå Fracture and Osteoporosis (UFO) study is a population-based nested case-control study investigating associations between lifestyle and fragility fractures. From a cohort of ~35,000 subjects, we identified 376 female wrist fracture cases who had reported data regarding their commuting habits, occupational, and leisure physical activity, before they sustained their fracture. Each fracture case was compared with at least one control drawn from the same cohort and matched for age and week of reporting data, yielding a total of 778 subjects. Mean age at baseline was 54.3 ± 5.8 years, and mean age at fracture was 60.3 ± 5.8 years. Conditional logistic regression analysis with adjustments for height, body mass index, smoking, and menopausal status showed that subjects with active commuting (especially walking) were at significantly lower risk of sustaining a wrist fracture (OR 0.48; 95 % CI 0.27-0.88) compared with those who commuted by car or bus. Leisure time activities such as dancing and snow shoveling were also associated with a lower fracture risk, whereas occupational activity, training, and leisure walking or cycling were unrelated to fracture risk. This study suggests that active commuting is associated with a lower wrist fracture risk, in middle-aged women.

Hypothyroxinemia During Gestation and Offspring Schizophrenia in a National Birth Cohort

PubMed Central

Gyllenberg, David; Sourander, Andre; Surcel, Heljä-Marja; Hinkka-Yli-Salomäki, Susanna; McKeague, Ian W.; Brown, Alan S.

2015-01-01

Background Evidence from animal and human studies indicates that thyroid hormone deficiency during early gestation alters brain development. As schizophrenia is associated with prenatal brain insults and premorbid cognitive deficits, we tested the a priori hypothesis that serologically defined maternal thyroid deficiency during early to mid-gestation is associated with offspring schizophrenia. Methods The investigation is based on the Finnish Prenatal Study of Schizophrenia (FiPS-S), a nested case-control study that included archived maternal sera from virtually all pregnancies since 1983 (total N over 1 million). We identified all offspring in the cohort diagnosed with schizophrenia based on the national inpatient and outpatient register and matched them to comparison subjects (1:1) from the cohort on sex, date of birth, and residence in Finland at time of onset of the case. Maternal sera on 1010 case-control pairs were assessed for free thyroxine (fT4) and 948 for thyroid stimulating hormone (TSH). Results Maternal hypothyroxinemia (fT4≤10th percentile, normal TSH) was associated with an increased odds of schizophrenia (OR=1.75, 95% CI=1.22 – 2.50; p=0.002). When adjusted for maternal psychiatric history, province of birth and maternal smoking during pregnancy, the association remained significant (OR=1.70, 95%CI 1.13 – 2.55; p=0.010). Conclusions In a large, national birth cohort, prospectively documented early to mid-gestational hypothyroxinemia was associated with increased odds of schizophrenia in offspring. This can inform translational studies of maternal hypothyroxinemia examining molecular and cellular deviations relevant to schizophrenia. PMID:26194598

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

PubMed Central

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

2011-01-01

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

Effects of phenotypes in heterocyclic aromatic amine (HCA) metabolism-related genes on the association of HCA intake with the risk of colorectal adenomas.

PubMed

Barbir, Aline; Linseisen, Jakob; Hermann, Silke; Kaaks, Rudolf; Teucher, Birgit; Eichholzer, Monika; Rohrmann, Sabine

2012-09-01

Heterocyclic aromatic amines (HCA), formed by high-temperature cooking of meat, are well-known risk factors for colorectal cancer (CRC). Enzymes metabolizing HCAs may influence the risk of CRC depending on the enzyme activity level. We aimed to assess effect modification by polymorphisms in the HCA-metabolizing genes on the association of HCA intake with colorectal adenoma (CRA) risk, which are precursors of CRC. A case-control study nested in the EPIC-Heidelberg cohort was conducted. Between 1994 and 2005, 413 adenoma cases were identified and 796 controls were matched to cases. Genotypes were determined and used to predict phenotypes (i.e., enzyme activities). Odds ratios (OR) and corresponding 95 % confidence intervals (CI) were calculated by logistic regression analysis. CRA risk was positively associated with PhIP, MeIQx, and DiMeIQx (p trend = 0.006, 0.022, and 0.045, respectively) intake. SULT1A1 phenotypes modified the effect of MeIQx on CRA risk (p (Interaction) > 0.01) such that the association of MeIQx intake with CRA was stronger for slow than for normal phenotypes. Other modifying effects by phenotypes did not reach statistical significance. HCA intake is positively associated with CRA risk, regardless of phenotypes involved in the metabolizing process. Due to the number of comparisons made in the analysis, the modifying effect of SULT1A1 on the association of HCA intake with CRA risk may be due to chance.

Is maternal smoking during pregnancy associated with bipolar disorder in offspring?

PubMed

Chudal, Roshan; Brown, Alan S; Gissler, Mika; Suominen, Auli; Sourander, Andre

2015-01-15

Prenatal smoking exposure affects fetal growth and development and is associated with increased risk of various neurodevelopmental disorders. Only one previous study has examined the association between maternal smoking during pregnancy and the risk of bipolar disorder (BPD). In this nested case control study derived from all singleton live births in Finland between January 1st 1987 and December 31st 1998, we identified 724 children diagnosed and/or treated with BPD until 2008 and 1419 matched controls from four nationwide registers. Conditional logistic regression was used to examine the association between maternal smoking during pregnancy and BPD adjusting for potential confounding due to parental psychiatric history, maternal age and education level. 18.5% of offspring were exposed to maternal smoking during pregnancy. In the unadjusted analysis, smoking during pregnancy was associated with a 1.41-fold (95% CI 1.12-1.79, P=0.004) increased risk of BPD. In the final model adjusting for potential covariates, the risk was 1.14-fold (95% CI 0.88-1.49, P=0.323). The limitations of this study include: hospital based clinical diagnosis for case ascertainment, inclusion of early onset BPD cases, and lack of information on alcohol or other substance abuse during pregnancy. This study demonstrated that, in this sample, an increased risk of BPD among offspring of mothers who smoked during pregnancy is most likely due to confounding by familial background factors. Future studies including information on serological measures of smoking exposure in pregnancy e.g. cotinine are warranted to further clarify this association. Copyright © 2014 Elsevier B.V. All rights reserved.

Risk factors for occupational acute mountain sickness.

PubMed

Vinnikov, D; Brimkulov, N; Krasotski, V; Redding-Jones, R; Blanc, P D

2014-10-01

Studies of occupational acute mountain sickness (AMS) have not focused on the more severe end of the spectrum to date. To examine risk factors associated with the development of occupational AMS severe enough to receive treatment in a compression chamber. A nested case referent study in a cohort of high-altitude (4000 m) mine workers, comparing cases of severe, chamber-treated AMS to matched referents. Using logistic regression, we tested potential risk factors based on premorbid surveillance examinations, including cigarette smoking (current smoking, smoking intensity and exhaled carbon monoxide [CO]). There were 15 cases and 30 controls. In multivariate analysis including age, sex and place of residence, current smoking was associated with increased risk of severe AMS (odds ratio [OR] 10.0; 95% confidence interval [CI] 1.5-67.4), taking into account any prior, less severe AMS event, which was also a potent risk factor (OR 33.3; 95% CI 2.8-390). Smoking intensity (cigarettes per day) and exhaled CO were also statistically significantly associated with severe AMS. Cigarette smoking is a strong, previously under-appreciated risk factor for severe AMS. Because this is a modifiable factor, these findings suggest that workplace-based smoking cessation should be tested as an intervention to prevent such morbidity. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prognostic value of vitamin D level for all-cause mortality, and association with inflammatory markers, in HIV-infected persons.

PubMed

Shepherd, Leah; Souberbielle, Jean-Claude; Bastard, Jean-Philippe; Fellahi, Soraya; Capeau, Jaqueline; Reekie, Joanne; Reiss, Peter; Blaxhult, Anders; Bickel, Markus; Leen, Clifford; Kirk, Ole; Lundgren, Jens D; Mocroft, Amanda; Viard, Jean-Paul

2014-07-15

Low 25-hydroxyvitamin D (25(OH)D) has been associated with inflammation, human immunodeficiency virus (HIV) disease progression, and death. We aimed to identify the prognostic value of 25(OH)D for AIDS, non-AIDS-defining events and death, and its association with immunological/inflammatory markers. Prospective 1-1 case-control study nested within the EuroSIDA cohort. Matched cases and controls for AIDS (n = 50 matched pairs), non-AIDS-defining (n = 63) events and death (n = 41), with plasma samples during follow-up were selected. Conditional logistic regression models investigated associations between 25(OH)D levels and annual 25(OH)D change and the probability of events. Mixed models investigated relationships between 25(OH)D levels and immunological/inflammatory markers. In sum, 250 patients were included. Median time between first and last sample and last sample and event was 44.6(interquartile range [IQR]: 22.7-72.3) and 3.1(IQR: 1.4-6.4) months. Odds of death decreased by 46.0%(95% confidence interval [CI], 2.0-70.0, P = .04) for a 2-fold increase in latest 25(OH)D level. There was no association between 25(OH)D and the occurrence of AIDS or non-AIDS-defining events (P > .05). In patients with current 25(OH)D <10 ng/mL, hsIL-6 concentration increased by 4.7%(95% CI, .2,9.4, P = .04) annually after adjustment for immunological/inflammatory markers, and no change in hsCRP rate was observed (P = .76). Low Vitamin D predicts short term mortality in HIV-positive persons. Effectiveness of vitamin D supplementation on inflammation and patient outcomes should be investigated. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Sibship size, birth order and risk of nasopharyngeal carcinoma and infectious mononucleosis: a nationwide study in Sweden.

PubMed

Liu, Zhiwei; Fang, Fang; Chang, Ellen T; Adami, Hans-Olov; Ye, Weimin

2016-06-01

The aetiology of nasopharyngeal carcinoma (NPC) remains enigmatic in endemic and non-endemic areas. Early-life infection with Epstein-Barr virus (EBV) may predispose to NPC development, whereas delayed primary infection with EBV may cause infectious mononucleosis (IM). We used Swedish population and health registers to investigate whether potential indicators of early EBV infection, such as birth order, sibship size, maternal age and paternal age, are related to the subsequent risks for NPC and IM. We conducted two nested case-control studies, one for each health outcome, based on 251 NPC case patients, 11 314 IM case patients and five population control subjects per case matched by birth year and sex. We used conditional logistic regression modelling to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for NPC and IM. The multivariate-adjusted ORs of developing NPC increased with number of siblings; the ORs associated with having one, two and three or more siblings, compared with none, were 1.59 (95% CI = 0.97, 2.62), 1.94 (95% CI = 1.17, 3.22), and 2.03 (95% CI = 1.23, 3.35), respectively (Ptrend = 0.006). This increased risk of NPC was explained mainly by having older rather than younger siblings. In contrast, lower risks of IM were observed among individuals with an increasing number of older siblings, younger siblings and total siblings. Early-life social environment, possibly related to EBV infection, contributes to NPC pathogenesis in non-endemic areas. This hypothesis is further supported by the clearly contrasting findings between NPC and IM. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Premenopausal circulating androgens and risk of endometrial cancer: Results of a prospective study

PubMed Central

Clendenen, Tess V.; Hertzmark, Kathryn; Koenig, Karen L.; Lundin, Eva; Rinaldi, Sabina; Johnson, Theron; Krogh, Vittorio; Hallmans, Göran; Idahl, Annika; Lukanova, Annekatrin; Zeleniuch-Jacquotte, Anne

2016-01-01

Endometrial cancer risk is increased by estrogens unopposed by progesterone. In premenopausal women, androgen excess is often associated with progesterone insufficiency, suggesting that premenopausal androgen concentrations may be associated with risk. In a case-control study nested within three cohorts, we assessed the relationship between premenopausal androgens and risk of endometrial cancer (161 cases and 303 controls matched on age and date of blood donation). Testosterone, DHEAS, androstenedione, and SHBG were measured in serum or plasma. Free testosterone was calculated from testosterone and SHBG. We observed trends of increasing risk across tertiles of testosterone (ORT3-T1: 1.59, 95%CI: 0.96, 2.64, p=0.08) and free testosterone (ORT3-T1: 1.76, 95%CI: 1.01, 3.07, p=0.047), which were not statistically significant after adjustment for body mass index (BMI). There was no association for DHEAS, androstenedione, or SHBG. There were significant interactions by age at diagnosis (<55 years, n=51 cases; ≥55 years, n=110 cases). Among women who were ≥55 years of age (predominantly postmenopausal) at diagnosis, the BMI-adjusted OR was 2.08 (95%CI: 1.25, 3.44, p=0.005) for a doubling in testosterone and 1.55 (95%CI: 1.04, 2.31, p=0.049) for a doubling in free testoterone. There was no association among women aged <55 years at diagnosis, consistent with the only other prospective study to date. If pre- and post-menopausal concentrations of androgens are correlated, our observation of an association of premenopausal androgens with risk among women aged ≥55 years at diagnosis could be due to the effect on the endometrium of postmenopausal androgen-derived estrogens in the absence of progesterone, which is no longer secreted. PMID:26925952