Generalizability of clinical trials of advanced melanoma in the real-world, population-based setting.

PubMed

Sam, Davis; Gresham, Gillian; Abdel-Rahman, Omar; Cheung, Winson Y

2018-06-18

Results from novel therapeutics trials are not always generalizable to real-world patients. We aimed to determine the pattern in which trial findings are applied in a population-based setting of melanoma patients and consequent treatment outcomes. Patients with unresectable disease during 2011-2014 and referred to cancer centers in a large Canadian province were retrospectively reviewed. Based on eligibility criteria as described in registration trials of vemurafenib (Vem) and ipilimumab (Ipi), we classified patients into trial-eligible and ineligible and those treated and untreated with these agents. We identified 290 patients with known BRAF status for the Vem analysis and 212 patients previously treated with first-line agents for the Ipi analysis. For the Vem cohort, a total of 49 patients were considered trial-eligible, of whom 36 (73%) received treatment. For the Ipi cohort, there were 119 trial-eligible cases of whom 43 (36%) received therapy. Factors other than eligibility criteria most frequently associated with non-treatment in these cohorts included concerns regarding treatment harm and patient preferences. In multivariable analysis, overall survival was improved in Vem cohort patients considered trial-eligible and treated compared to those who were ineligible. Within the Ipi cohort, survival was improved in trial-eligible patients regardless of whether they received Ipi compared to ineligible patients. Real-world uptake of new melanoma treatments was suboptimal, and non-use in trial-eligible patients was frequent. Future clinical trials that are more pragmatically designed to include participants who better reflect the real-world population may facilitate increased uptake of novel therapeutics into routine clinical practice.

In response to the December 2016 article entitled "Vegetarian diet and all-cause mortality: Evidence from a large population-based Australian cohort - the 45 and Up Study".

PubMed

Taylor, Nathan G A

2017-07-01

In response to the December 2016 article entitled "Vegetarian diet and all-cause mortality: Evidence from a large population-based Australian cohort - the 45 and Up Study". A brief analysis of the article with suggestions for interpretation and considerations for future research. Copyright © 2017 Elsevier Inc. All rights reserved.

The structure of the Hospital Anxiety and Depression Scale in four cohorts of community-based, healthy older people: the HALCyon program.

PubMed

Gale, Catharine R; Allerhand, Michael; Sayer, Avan Aihie; Cooper, Cyrus; Dennison, Elaine M; Starr, John M; Ben-Shlomo, Yoav; Gallacher, John E; Kuh, Diana; Deary, Ian J

2010-06-01

The Hospital Anxiety and Depression Scale (HADS) is widely used but evaluation of its psychometric properties has produced equivocal results. Little is known about its structure in non-clinical samples of older people. We used data from four cohorts in the HALCyon collaborative research program into healthy aging: the Caerphilly Prospective Study, the Hertfordshire Ageing Study, the Hertfordshire Cohort Study, and the Lothian Birth Cohort 1921. We used exploratory factor analysis and confirmatory factor analysis with multi-group comparisons to establish the structure of the HADS and test for factorial invariance between samples. Exploratory factor analysis showed a bi-dimensional structure (anxiety and depression) of the scale in men and women in each cohort. We tested a hypothesized three-factor model but high correlations between two of the factors made a two-factor model more psychologically plausible. Multi-group confirmatory factor analysis revealed that the sizes of the respective item loadings on the two factors were effectively identical in men and women from the same cohort. There was more variation between cohorts, particularly those from different parts of the U.K. and in whom the HADS was administered differently. Differences in social-class distribution accounted for part of this variation. Scoring the HADS as two subscales of anxiety and depression is appropriate in non-clinical populations of older men and women. However, there were differences between cohorts in the way that individual items were linked with the constructs of anxiety and depression, perhaps due to differences in sociocultural factors and/or in the administration of the scale.

An Automatic Approach for Analyzing Treatment Effectiveness Based on Medication Hierarchy - The Myocardial Infarction Case Study.

PubMed

Li, Yingxue; Hu, Yiying; Yang, Jingang; Li, Xiang; Liu, Haifeng; Xie, Guotong; Xu, Meilin; Hu, Jingyi; Yang, Yuejin

2017-01-01

Treatment effectiveness plays a fundamental role in patient therapies. In most observational studies, researchers often design an analysis pipeline for a specific treatment based on the study cohort. To evaluate other treatments in the data set, much repeated and multifarious work including cohort construction, statistical analysis need to be done. In addition, as treatments are often with an intrinsic hierarchical relationship, many rational comparable treatment pairs can be derived as new treatment variables besides the original single treatment one from the original cohort data set. In this paper, we propose an automatic treatment effectiveness analysis approach to solve this problem. With our approach, clinicians can assess the effect of treatments not only more conveniently but also more thoroughly and comprehensively. We applied this method to a real world case of estimating the drug effectiveness on Chinese Acute Myocardial Infarction (CAMI) data set and some meaningful results are obtained for potential improvement of patient treatments.

Estimation of risk of cancers before occurrence of acquired immunodeficiency syndrome in persons infected with human immunodeficiency virus.

PubMed

Li, Yueming; Law, Matthew; McDonald, Ann; Correll, Patty; Kaldor, John M; Grulich, Andrew E

2002-01-15

There is methodological debate as to whether cohorts defined by acquired immunodeficiency syndrome (AIDS) diagnosis can be used to estimate risks of cancer in persons with human immunodeficiency virus (HIV) before AIDS. The authors compared risks of non-AIDS-defining cancers before AIDS in persons with HIV using a cohort based on AIDS diagnosis and a second cohort based on HIV diagnosis. National population-based registries of AIDS and HIV diagnoses to August 1999 were matched separately with the National Cancer Registry in Australia. Four analyses were performed. In analysis 1, follow-up was from 5 years before AIDS registration in 8,118 persons with AIDS. Analysis 2 was similar but adjusted expected numbers of cancers for decreased survival. Analysis 3 was based on 7,061 persons registered with HIV, with follow-up from the reported date of diagnosis. Analysis 4 was based on 2,112 AIDS cases previously reported with HIV, with follow-up from 5 years before AIDS diagnosis. In all analyses, follow-up ended at cancer diagnosis, death, 6 months before AIDS, or the end of available cancer data, whichever occurred first. For 10 types of cancer there were at least three cases in any one of the analyses. For these cancers there was no systematic pattern such that one analysis produced consistently higher or lower estimates than the others. These analyses suggest that cancer risk in persons with HIV before AIDS diagnosis may be estimated reliably based on cancer experience 5 years before AIDS.

A cohort mortality study of employees exposed to chlorinated chemicals.

PubMed

Wong, O

1988-01-01

The cohort of this historical prospective mortality study consisted of 697 male employees at a chlorination plant. A majority of the cohort was potentially exposed to benzotrichloride, benzyl chloride, benzoyl chloride, and other related chemicals. The mortality experience of the cohort was observed from 1943 through 1982. For the cohort as a whole, no statistically significant mortality excess was detected. The overall Standardized Mortality Ratio (SMR) was 100, and the SMR for all cancers combined was 122 (not significant). The respiratory cancer SMR for the cohort as a whole was 246 (7 observed vs. 2.8 expected). The excess was of borderline statistical significance, the lower 95% confidence limit being 99. Analysis by race showed that all 7 respiratory cancer deaths came from the white male employees, with an SMR of 265 (p less than 0.05). The respiratory cancer mortality excess was higher among employees in maintenance (SMR = 229) than among those in operations or production (SMR = 178). The lung cancer mortality excess among the laboratory employees was statistically significant (SMR = 1292). However, this observation should be viewed with caution, since it was based on only 2 deaths. Further analysis indicated that the respiratory cancer mortality excess was limited to the male employees with 15 or more years of employment (SMR = 379, p less than 0.05). Based on animal data as well as other epidemiologic studies, together with the internal consistency of analysis by length of employment, the data suggest an association between the chlorination process of toluene at the plant and an increased risk of respiratory cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Statin use and survival in colorectal cancer: Results from a population-based cohort study and an updated systematic review and meta-analysis.

PubMed

Gray, Ronan T; Coleman, Helen G; Hughes, Carmel; Murray, Liam J; Cardwell, Chris R

2016-12-01

The aim of this study was to investigate the association between statin use and survival in a population-based colorectal cancer (CRC) cohort and perform an updated meta-analysis to quantify the magnitude of any association. A cohort of 8391 patients with newly diagnosed Dukes' A-C CRC (2009-2012) was identified from the Scottish Cancer Registry. This cohort was linked to the Prescribing Information System and the National Records of Scotland Death Records (until January 2015) to identify 1064 colorectal cancer-specific deaths. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by statin use were calculated using time dependent Cox regression models. The systematic review included relevant studies published before January 2016. Meta-analysis techniques were used to derive combined HRs for associations between statin use and cancer-specific and overall mortality. In the Scottish cohort, statin use before diagnosis (HR=0.84, 95% CI 0.75-0.94), but not after (HR=0.90, 95% CI 0.77-1.05), was associated with significantly improved cancer-specific mortality. The systematic review identified 15 relevant studies. In the meta-analysis, there was consistent (I 2 =0%,heterogeneity P=0.57) evidence of a reduction in cancer-specific mortality with statin use before diagnosis in 6 studies (n=86,622, pooled HR=0.82, 95% CI 0.79-0.86) but this association was less apparent and more heterogeneous (I 2 =67%,heterogeneity P=0.03) with statin use after diagnosis in 4 studies (n=19,152, pooled HR=0.84, 95% CI 0.68-1.04). In a Scottish CRC cohort and updated meta-analysis there was some evidence that statin use was associated with improved survival. However, these associations were weak in magnitude and, particularly for post-diagnosis use, varied markedly between studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Novel risk score of contrast-induced nephropathy after percutaneous coronary intervention.

PubMed

Ji, Ling; Su, XiaoFeng; Qin, Wei; Mi, XuHua; Liu, Fei; Tang, XiaoHong; Li, Zi; Yang, LiChuan

2015-08-01

Contrast-induced nephropathy (CIN) post-percutaneous coronary intervention (PCI) is a major cause of acute kidney injury. In this study, we established a comprehensive risk score model to assess risk of CIN after PCI procedure, which could be easily used in a clinical environment. A total of 805 PCI patients, divided into analysis cohort (70%) and validation cohort (30%), were enrolled retrospectively in this study. Risk factors for CIN were identified using univariate analysis and multivariate logistic regression in the analysis cohort. Risk score model was developed based on multiple regression coefficients. Sensitivity and specificity of the new risk score system was validated in the validation cohort. Comparisons between the new risk score model and previous reported models were applied. The incidence of post-PCI CIN in the analysis cohort (n = 565) was 12%. Considerably high CIN incidence (50%) was observed in patients with chronic kidney disease (CKD). Age >75, body mass index (BMI) >25, myoglobin level, cardiac function level, hypoalbuminaemia, history of chronic kidney disease (CKD), Intra-aortic balloon pump (IABP) and peripheral vascular disease (PVD) were identified as independent risk factors of post-PCI CIN. A novel risk score model was established using multivariate regression coefficients, which showed highest sensitivity and specificity (0.917, 95%CI 0.877-0.957) compared with previous models. A new post-PCI CIN risk score model was developed based on a retrospective study of 805 patients. Application of this model might be helpful to predict CIN in patients undergoing PCI procedure. © 2015 Asian Pacific Society of Nephrology.

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

PubMed

Keogh, Ruth H; White, Ian R

2013-10-15

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

Trends in Dementia Incidence in a Birth Cohort Analysis of the Einstein Aging Study.

PubMed

Derby, Carol A; Katz, Mindy J; Lipton, Richard B; Hall, Charles B

2017-11-01

Trends in dementia incidence rates have important implications for planning and prevention. To better understand incidence trends over time requires separation of age and cohort effects, and few prior studies have used this approach. To examine trends in dementia incidence and concomitant trends in cardiovascular comorbidities among individuals aged 70 years or older who were enrolled in the Einstein Aging Study between 1993 and 2015. In this birth cohort analysis of all-cause dementia incidence in persons enrolled in the Einstein Aging Study from October 20, 1993, through November 17, 2015, a systematically recruited, population-based sample of 1348 participants from Bronx County, New York, who were 70 years or older without dementia at enrollment and at least one annual follow-up was studied. Poisson regression was used to model dementia incidence as a function of age, sex, educational level, race, and birth cohort, with profile likelihood used to identify the timing of significant increases or decreases in incidence. Birth year and age. Incident dementia defined by consensus case conference based on annual, standardized neuropsychological and neurologic examination findings, using criteria from the DSM-IV. Among 1348 individuals (mean [SD] baseline age, 78.5 [5.4] years; 830 [61.6%] female; 915 [67.9%] non-Hispanic white), 150 incident dementia cases developed during 5932 person-years (mean [SD] follow-up, 4.4 [3.4] years). Dementia incidence decreased in successive birth cohorts. Incidence per 100 person-years was 5.09 in birth cohorts before 1920, 3.11 in the 1920 through 1924 birth cohorts, 1.73 in the 1925 through 1929 birth cohorts, and 0.23 in cohorts born after 1929. Change point analyses identified a significant decrease in dementia incidence among those born after July 1929 (95% CI, June 1929 to January 1930). The relative rate for birth cohorts before July 1929 vs after was 0.13 (95% CI, 0.04-0.41). Prevalence of stroke and myocardial infarction decreased across successive birth cohorts, whereas diabetes prevalence increased. Adjustment for these cardiovascular comorbidities did not explain the decreased dementia incidence rates for more recent birth cohorts. Analyses confirm decreasing dementia incidence in this population-based sample. Whether decreasing incidence will contribute to reduced burden of dementia given the aging of the population is not known.

Shiny FHIR: An Integrated Framework Leveraging Shiny R and HL7 FHIR to Empower Standards-Based Clinical Data Applications.

PubMed

Hong, Na; Prodduturi, Naresh; Wang, Chen; Jiang, Guoqian

2017-01-01

In this study, we describe our efforts in building a clinical statistics and analysis application platform using an emerging clinical data standard, HL7 FHIR, and an open source web application framework, Shiny. We designed two primary workflows that integrate a series of R packages to enable both patient-centered and cohort-based interactive analyses. We leveraged Shiny with R to develop interactive interfaces on FHIR-based data and used ovarian cancer study datasets as a use case to implement a prototype. Specifically, we implemented patient index, patient-centered data report and analysis, and cohort analysis. The evaluation of our study was performed by testing the adaptability of the framework on two public FHIR servers. We identify common research requirements and current outstanding issues, and discuss future enhancement work of the current studies. Overall, our study demonstrated that it is feasible to use Shiny for implementing interactive analysis on FHIR-based standardized clinical data.

A Comparative Analysis of Learning Tactics Employed in the Workplace by Leaders from Emerging Generational Cohorts

ERIC Educational Resources Information Center

DePinto, Ross M.

2013-01-01

Much of the relevant literature in the domains of leadership development, succession planning, and cross-generational issues that discusses learning paradigms associated with emerging generational cohorts has been based on qualitative research and anecdotal evidence. In contrast, this study employed quantitative research methods using a validated…

A New Genomewide Association Meta-Analysis of Alcohol Dependence.

PubMed

Zuo, Lingjun; Tan, Yunlong; Zhang, Xiangyang; Wang, Xiaoping; Krystal, John; Tabakoff, Boris; Zhong, Chunlong; Luo, Xingguang

2015-08-01

Conventional meta-analysis based on genetic markers may be less powerful for heterogeneous samples. In this study, we introduced a new meta-analysis for 4 genomewide association studies on alcohol dependence that integrated the information of putative causal variants. A total of 12,481 subjects in 4 independent cohorts were analyzed, including 1 European American cohort (1,409 cases with alcohol dependence and 1,518 controls), 1 European Australian cohort (a total of 6,438 family subjects with 1,645 probands), 1 African American cohort from SAGE + COGA (681 cases and 508 controls), and 1 African American cohort from Yale (1,429 cases and 498 controls). The genomewide association analysis was conducted for each cohort, and then, a new meta-analysis was performed to derive the combined p-values. cis-Acting expression of quantitative locus (cis-eQTL) analysis of each risk variant in human tissues and RNA expression analysis of each risk gene in rat brain served as functional validation. In meta-analysis of European American and European Australian cohorts, we found 10 top-ranked single nucleotide polymorphisms (SNPs) (p < 10(-6) ) that were associated with alcohol dependence. They included 6 at SERINC2 (3.1 × 10(-8) ≤ p ≤ 9.6 × 10(-8) ), 1 at STK40 (p = 1.3 × 10(-7) ), 2 at KIAA0040 (3.3 × 10(-7) ≤ p ≤ 5.2 × 10(-7) ), and 1 at IPO11 (p = 6.9 × 10(-7) ). In meta-analysis of 2 African American cohorts, we found 2 top-ranked SNPs including 1 at SLC6A11 (p = 2.7 × 10(-7) ) and 1 at CBLN2 (p = 7.4 × 10(-7) ). In meta-analysis of all 4 cohorts, we found 2 top-ranked SNPs in PTP4A1-PHF3 locus (6.0 × 10(-7) ≤ p ≤ 7.2 × 10(-7) ). In an African American cohort only, we found 1 top-ranked SNP at PLD1 (p = 8.3 × 10(-7) ; OR = 1.56). Many risk SNPs had positive cis-eQTL signals, and all these risk genes except KIAA0040 were found to express in both rat and mouse brains. We found multiple genes that were significantly or suggestively associated with alcohol dependence. They are among the most appropriate for follow-up as contributors to risk for alcohol dependence. Copyright © 2015 by the Research Society on Alcoholism.

Longitudinal Commercial Claims-Based Cost Analysis of Diabetic Retinopathy Screening Patterns.

PubMed

Fitch, Kathryn; Weisman, Thomas; Engel, Tyler; Turpcu, Adam; Blumen, Helen; Rajput, Yamina; Dave, Purav

2015-09-01

Diabetic retinopathy is one of the most common complications of diabetes. The screening of patients with diabetes to detect retinopathy is recommended by several professional guidelines but is an underutilized service. To analyze the relationship between the frequency of retinopathy screening and the cost of care in adult patients with diabetes. Truven Health MarketScan commercial databases (2000-2013) were used to identify the diabetic population aged 18 to 64 years for the performance of a 2001-2013 annual trend analysis of patients with type 1 and type 2 diabetes and a 10-year longitudinal analysis of patients with newly diagnosed type 2 diabetes. In the trend analysis, the prevalence of diabetes, screening rate, and allowed cost per member per month (PMPM) were calculated. In the longitudinal analysis, data from 4 index years (2001-2004) of patients newly diagnosed with type 2 diabetes were combined, and the costs were adjusted to be comparable to the 2004 index year cohort, using the annual diabetes population cost trends calculated in the trend analysis. The longitudinal population was segmented into the number of years of diabetic retinopathy screening (ie, 0, 1-4, 5-7, and 8-10), and the relationship between the years of screening and the PMPM allowed costs was analyzed. The difference in mean incremental cost between years 1 and 10 in each of the 4 cohorts was compared after adjusting for explanatory variables. In the trend analysis, between 2001 and 2013, the prevalence of diabetes increased from 3.93% to 5.08%, retinal screening increased from 26.27% to 29.58%, and the average total unadjusted allowed cost of care for each patient with diabetes increased from $822 to $1395 PMPM. In the longitudinal analysis, the difference between the screening cohorts' mean incremental cost increase was $185 between the 0- and 1-4-year cohorts (P <.003) and $202 between the 0- and 5-7-year cohorts (P <.023). The cost differences between the other cohorts, including $217 between the 0- and 8-10-year cohorts (P <.066), were not statistically significant. Based on our analysis, the annual retinopathy screening rate for patients with diabetes has remained low since 2001, and has been well below the guideline-recommended screening levels. For patients with type 2 diabetes, the mean increase in healthcare expenditures over a 10-year period after diagnosis is not statistically different among those with various retinopathy screening rates, although the increase in healthcare spending is lower for patients with diabetes who were not screened for retinopathy compared with patients who did get screened.

Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies.

PubMed

Jess, Tine; Rungoe, Christine; Peyrin-Biroulet, Laurent

2012-06-01

Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC). Studies examining the magnitude of this association have yielded conflicting results. We performed a meta-analysis of population-based cohort studies to determine the risk of CRC in patients with UC. We used MEDLINE, EMBASE, Cochrane, and CINAHL to perform a systematic literature search. We included 8 studies in the meta-analysis on the basis of strict inclusion and exclusion criteria. We calculated pooled standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for risk of CRC in patients with UC and performed meta-regression analyses of the effect of cohort size, calendar period, observation time, percentage with proctitis, and rates of colectomy on the risk of CRC. An average of 1.6% of patients with UC was diagnosed with CRC during 14 years of follow-up. SIRs ranged from 1.05 to 3.1, with a pooled SIR of 2.4 (95% CI, 2.1-2.7). Men with UC had a greater risk of CRC (SIR, 2.6; 95% CI, 2.2-3.0) than women (SIR, 1.9; 95% CI, 1.5-2.3). Young age was a risk factor for CRC (SIR, 8.6; 95% CI, 3.8-19.5; although this might have resulted from small numbers), as was extensive colitis (SIR, 4.8; 95% CI, 3.9-5.9). In meta-regression analyses, only cohort size was associated with risk of CRC. In population-based cohorts, UC increases the risk of CRC 2.4-fold. Male sex, young age at diagnosis with UC, and extensive colitis increase the risk. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

How was the intern year?: self and clinical assessment of four cohorts, from two medical curricula

PubMed Central

2014-01-01

Background Problem-based curricula have provoked controversy amongst educators and students regarding outcome in medical graduates, supporting the need for longitudinal evaluation of curriculum change. As part of a longitudinal evaluation program at the University of Adelaide, a mixed method approach was used to compare the graduate outcomes of two curriculum cohorts: traditional lecture-based ‘old’ and problem-based ‘new’ learning. Methods Graduates were asked to self-assess preparedness for hospital practice and consent to a comparative analysis of their work-place based assessments from their intern year. Comparative data were extracted from 692 work-place based assessments for 124 doctors who graduated from the University of Adelaide Medical School between 2003 and 2006. Results Self-assessment: Overall, graduates of the lecture-based curriculum rated the medical program significantly higher than graduates of the problem-based curriculum. However, there was no significant difference between the two curriculum cohorts with respect to their preparedness in 13 clinical skills. There were however, two areas where the cohorts rated their preparedness in the 13 broad practitioner competencies as significantly different: problem-based graduates rated themselves as better prepared in their ‘awareness of legal and ethical issues’ and the lecture-based graduates rated themselves better prepared in their ‘understanding of disease processes’. Work-place based assessment: There were no significant differences between the two curriculum cohorts for ‘Appropriate Level of Competence’ and ‘Overall Appraisal’. Of the 14 work-place based assessment skills assessed for competence, no significant difference was found between the cohorts. Conclusions The differences in the perceived preparedness for hospital practice of two curriculum cohorts do not reflect the work-place based assessments of their competence as interns. No significant difference was found between the two cohorts in relation to their knowledge and clinical skills. However results suggest a trend in ‘communication with peers and colleagues in other disciplines’ (χ2 (3, N = 596) =13.10, p = 0.056) that requires further exploration. In addition we have learned that student confidence in a new curriculum may impact on their self-perception of preparedness, while not affecting their actual competence. PMID:24961171

Candida infective endocarditis: an observational cohort study with a focus on therapy.

PubMed

Arnold, Christopher J; Johnson, Melissa; Bayer, Arnold S; Bradley, Suzanne; Giannitsioti, Efthymia; Miró, José M; Tornos, Pilar; Tattevin, Pierre; Strahilevitz, Jacob; Spelman, Denis; Athan, Eugene; Nacinovich, Francisco; Fortes, Claudio Q; Lamas, Cristiane; Barsic, Bruno; Fernández-Hidalgo, Nuria; Muñoz, Patricia; Chu, Vivian H

2015-04-01

Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Candida Infective Endocarditis: an Observational Cohort Study with a Focus on Therapy

PubMed Central

Johnson, Melissa; Bayer, Arnold S.; Bradley, Suzanne; Giannitsioti, Efthymia; Miró, José M.; Tornos, Pilar; Tattevin, Pierre; Strahilevitz, Jacob; Spelman, Denis; Athan, Eugene; Nacinovich, Francisco; Fortes, Claudio Q.; Lamas, Cristiane; Barsic, Bruno; Fernández-Hidalgo, Nuria; Muñoz, Patricia; Chu, Vivian H.

2015-01-01

Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis. PMID:25645855

PRImary care Streptococcal Management (PRISM) study: identifying clinical variables associated with Lancefield group A β-haemolytic streptococci and Lancefield non-Group A streptococcal throat infections from two cohorts of patients presenting with an acute sore throat

PubMed Central

Little, Paul; Moore, Michael; Hobbs, F D R; Mant, David; McNulty, Cliodna; Williamson, Ian; Cheng, Edith; Stuart, Beth; Kelly, Joanne; Barnett, Jane; Mullee, Mark

2013-01-01

Objective To assess the association between features of acute sore throat and the growth of streptococci from culturing a throat swab. Design Diagnostic cohort. Setting UK general practices. Participants Patients aged 5 or over presenting with an acute sore throat. Patients were recruited for a second cohort (cohort 2, n=517) consecutively after the first (cohort 1, n=606) from similar practices. Main outcome Predictors of the presence of Lancefield A/C/G streptococci. Results The clinical score developed from cohort 1 had poor discrimination in cohort 2 (bootstrapped estimate of area under the receiver operator characteristic (ROC) curve (0.65), due to the poor validity of the individual items in the second data set. Variables significant in multivariate analysis in both cohorts were rapid attendance (prior duration 3 days or less; multivariate adjusted OR 1.92 cohort, 1.67 cohort 2); fever in the last 24 h (1.69, 2.40); and doctor assessment of severity (severely inflamed pharynx/tonsils (2.28, 2.29)). The absence of coryza or cough and purulent tonsils were significant in univariate analysis in both cohorts and in multivariate analysis in one cohort. A five-item score based on Fever, Purulence, Attend rapidly (3 days or less), severely Inflamed tonsils and No cough or coryza (FeverPAIN) had moderate predictive value (bootstrapped area under the ROC curve 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection (38% in cohort 1, 36% in cohort 2 scored ≤1, associated with a streptococcal percentage of 13% and 18%, respectively). A Centor score of ≤1 identified 23% and 26% of participants with streptococcal percentages of 10% and 28%, respectively. Conclusions Items widely used to help identify streptococcal sore throat may not be the most consistent. A modified clinical scoring system (FeverPAIN) which requires further validation may be clinically helpful in identifying individuals who are unlikely to have major pathogenic streptococci. PMID:24163209

PRImary care Streptococcal Management (PRISM) study: identifying clinical variables associated with Lancefield group A β-haemolytic streptococci and Lancefield non-Group A streptococcal throat infections from two cohorts of patients presenting with an acute sore throat.

PubMed

Little, Paul; Moore, Michael; Hobbs, F D R; Mant, David; McNulty, Cliodna; Williamson, Ian; Cheng, Edith; Stuart, Beth; Kelly, Joanne; Barnett, Jane; Mullee, Mark

2013-10-25

To assess the association between features of acute sore throat and the growth of streptococci from culturing a throat swab. Diagnostic cohort. UK general practices. Patients aged 5 or over presenting with an acute sore throat. Patients were recruited for a second cohort (cohort 2, n=517) consecutively after the first (cohort 1, n=606) from similar practices. Predictors of the presence of Lancefield A/C/G streptococci. The clinical score developed from cohort 1 had poor discrimination in cohort 2 (bootstrapped estimate of area under the receiver operator characteristic (ROC) curve (0.65), due to the poor validity of the individual items in the second data set. Variables significant in multivariate analysis in both cohorts were rapid attendance (prior duration 3 days or less; multivariate adjusted OR 1.92 cohort, 1.67 cohort 2); fever in the last 24 h (1.69, 2.40); and doctor assessment of severity (severely inflamed pharynx/tonsils (2.28, 2.29)). The absence of coryza or cough and purulent tonsils were significant in univariate analysis in both cohorts and in multivariate analysis in one cohort. A five-item score based on Fever, Purulence, Attend rapidly (3 days or less), severely Inflamed tonsils and No cough or coryza (FeverPAIN) had moderate predictive value (bootstrapped area under the ROC curve 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection (38% in cohort 1, 36% in cohort 2 scored ≤1, associated with a streptococcal percentage of 13% and 18%, respectively). A Centor score of ≤1 identified 23% and 26% of participants with streptococcal percentages of 10% and 28%, respectively. Items widely used to help identify streptococcal sore throat may not be the most consistent. A modified clinical scoring system (FeverPAIN) which requires further validation may be clinically helpful in identifying individuals who are unlikely to have major pathogenic streptococci.

Red and processed meat consumption and risk of glioma in adults: A systematic review and meta-analysis of observational studies

PubMed Central

Saneei, Parvane; Willett, Walter; Esmaillzadeh, Ahmad

2015-01-01

Background: These findings from several observational studies, investigated the association between red meat consumption and gliomas, were inconsistent. We conducted a systematic review and meta-analysis of observational studies to summarize available date on the relation between meat intake and risk of glioma. Materials and Methods: A systematic literature search of relevant reports published until May 2014 of the PubMed/Medline, ISI Web of Knowledge, Excerpta Medica database, Ovid database, Google Scholar, and Scopus databases was conducted. From 723 articles yielded in the preliminary literature search, data from eighteen publications (14 case-control, three cohort, and one nested case-control study) on unprocessed red meat, processed meat, and/or total red meat consumption in relation to glioma in adults were included in the analysis. Quality assessment of studies was performed. Random effects model was used to conduct the meta-analysis. Results: We found a positive significant association between unprocessed red meat intake and risk of glioma (relative risk [RR] = 1.30; 95% confidence interval [CI]: 1.08-1.58) after excluding three studies with uncertain type of brain cancer. This analysis included only one cohort study which revealed no relation between unprocessed red meat intake and glioma (RR = 1.75; 95% CI: 0.35-8.77). Consumption of processed meats was not related to increased risk of glioma in population-based case-control studies (RR = 1.26; 95% CI: 1.05-1.51) and reduced risk in hospital-based case-controls (RR = 0.79; 95% CI: 0.65-0.97). No significant association was seen between processed red meat intake and risk of glioma in cohort studies (RR: 1.08; 95% CI: 0.84-1.37). Total red meat consumption was not associated with risk of adult glioma in case-control or cohort studies. Conclusion: In this meta-analysis of 18 observational studies, we found a modest positive association between unprocessed red meat intake and risk of gliomas based almost entirely on case-control studies. Processed red meat was overall not associated with risk of gliomas in case-control or cohort studies. PMID:26600837

Can Comprehensive Chromosome Screening Technology Improve IVF/ICSI Outcomes? A Meta-Analysis

PubMed Central

Quan, Song

2015-01-01

Objective To examine whether comprehensive chromosome screening (CCS) for preimplantation genetic screening (PGS) has an effect on improving in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes compared to traditional morphological methods. Methods A literature search was conducted in PubMed, EMBASE, CNKI and ClinicalTrials.gov up to May 2015. Two reviewers independently evaluated titles and abstracts, extracted data and assessed quality. We included studies that compared the IVF/ICSI outcomes of CCS-based embryo selection with those of the traditional morphological method. Relative risk (RR) values with corresponding 95% confidence intervals (CIs) were calculated in RevMan 5.3, and subgroup analysis and Begg’s test were used to assess heterogeneity and potential publication bias, respectively. Results Four RCTs and seven cohort studies were included. A meta-analysis of the outcomes showed that compared to morphological criteria, euploid embryos identified by CCS were more likely to be successfully implanted (RCT RR 1.32, 95% CI 1.18–1.47; cohort study RR 1.74, 95% CI 1.35–2.24). CCS-based PGS was also related to an increased clinical pregnancy rate (RCT RR 1.26, 95% CI 0.83–1.93; cohort study RR 1.48, 95% CI 1.20–1.83), an increased ongoing pregnancy rate (RCT RR 1.31, 95% CI 0.64–2.66; cohort study RR 1.61, 95% CI 1.30–2.00), and an increased live birth rate (RCT RR 1.26, 95% CI 1.05–1.50; cohort study RR 1.35, 95% CI 0.85–2.13) as well as a decreased miscarriage rate (RCT RR 0.53, 95% CI 0.24–1.15; cohort study RR 0.31, 95% CI 0.21–0.46) and a decreased multiple pregnancy rate (RCT RR 0.02, 95% CI 0.00–0.26; cohort study RR 0.19, 95% CI 0.07–0.51). The results of the subgroup analysis also showed a significantly increased implantation rate in the CCS group. Conclusions The effectiveness of CCS-based PGS is comparable to that of traditional morphological methods, with better outcomes for women receiving IVF/ICSI technology. The transfer of both trophectoderm-biopsied and blastomere-biopsied CCS-euploid embryos can improve the implantation rate. PMID:26470028

Has there been a change in the natural history of Crohn's disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009.

PubMed

Lakatos, Peter Laszlo; Golovics, Petra Anna; David, Gyula; Pandur, Tunde; Erdelyi, Zsuzsanna; Horvath, Agnes; Mester, Gabor; Balogh, Mihaly; Szipocs, Istvan; Molnar, Csaba; Komaromi, Erzsebet; Veres, Gabor; Lovasz, Barbara Dorottya; Szathmari, Miklos; Kiss, Lajos S; Lakatos, Laszlo

2012-04-01

Medical therapy for Crohn's disease (CD) has changed significantly over the past 20 years with increasing use of immunosuppressives. In contrast, surgery rates are still high and there is little evidence that disease outcomes for CD have changed over the past decades. The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprem province database. Data of 506 incident CD patients were analyzed (age at diagnosis: 31.5 years, s.d. 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups by the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008). Overall, azathioprine (AZA), systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1- and 5-year probability of AZA use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In a multivariate Cox-regression analysis, decade of diagnosis (P < 0.001, hazard ratio (HR)(cohorts B-C): 2.88-6.53), age at onset (P = 0.008, HR: 1.76), disease behavior at diagnosis (P < 0.001, HR(complicated): 1.76-2.07), and need for systemic steroids (P < 0.001, HR: 2.71) were significantly associated with the time to initiation of AZA therapy. Early AZA use was significantly associated with the time to intestinal surgery in CD patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for AZA use (HR: 0.42, 95% CI: 0.26-0.67). This population-based inception cohort has shown that the recent reduction in surgical rates was independently associated with increased and earlier AZA use.

Introducing a novel highly prognostic grading scheme based on tumour budding and cell nest size for squamous cell carcinoma of the uterine cervix.

PubMed

Jesinghaus, Moritz; Strehl, Johanna; Boxberg, Melanie; Brühl, Frido; Wenzel, Adrian; Konukiewitz, Björn; Schlitter, Anna M; Steiger, Katja; Warth, Arne; Schnelzer, Andreas; Kiechle, Marion; Beckmann, Matthias W; Noske, Aurelia; Hartmann, Arndt; Mehlhorn, Grit; Koch, Martin C; Weichert, Wilko

2018-04-01

A novel histopathological grading system based on tumour budding and cell nest size has recently been shown to outperform conventional (WHO-based) grading algorithms in several tumour entities such as lung, oral, and oesophageal squamous cell carcinoma (SCC) in terms of prognostic patient stratification. Here, we tested the prognostic value of this innovative grading approach in two completely independent cohorts of SCC of the uterine cervix. To improve morphology-based grading, we investigated tumour budding activity and cell nest size as well as several other histomorphological factors (e.g., keratinization, nuclear size, mitotic activity) in a test cohort (n = 125) and an independent validation cohort (n = 122) of cervical SCC. All parameters were correlated with clinicopathological factors and patient outcome. Small cell nest size and high tumour budding activity were strongly associated with a dismal patient prognosis (p < 0.001 for overall survival [OS], disease-specific survival, and disease-free survival; test cohort) in both cohorts of cervical SCC. A novel grading algorithm combining these two parameters proved to be a highly effective, stage-independent prognosticator in both cohorts (OS: p < 0.001, test cohort; p = 0.001, validation cohort). In the test cohort, multivariate statistical analysis of the novel grade revealed that the hazard ratio (HR) for OS was 2.3 for G2 and 5.1 for G3 tumours compared to G1 neoplasms (p = 0.010). In the validation cohort, HR for OS was 3.0 for G2 and 7.2 for G3 tumours (p = 0.012). In conclusion, our novel grading algorithm incorporating cell nest size and tumour budding allows strongly prognostic histopathological grading of cervical SCC superior to WHO-based grading. Therefore, our data can be regarded as a cross-organ validation of previous results demonstrated for oesophageal, lung, and oral SCC. We suggest this grading algorithm as an additional morphology-based parameter for the routine diagnostic assessment of this tumour entity. © 2018 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.

Switching From Age-Based Stimulus Dosing to Dose Titration Protocols in Electroconvulsive Therapy: Empirical Evidence for Better Patient Outcomes With Lower Peak and Cumulative Energy Doses.

PubMed

O'Neill-Kerr, Alex; Yassin, Anhar; Rogers, Stephen; Cornish, Janie

2017-09-01

The aim of this study was to test the proposition that adoption of a dose titration protocol may be associated with better patient outcomes, at lower treatment dose, and with comparable cumulative dose to that in patients treated using an age-based stimulus dosing protocol. This was an analysis of data assembled from archived records and based on cohorts of patients treated respectively on an age-based stimulus dosing protocol and on a dose titration protocol in the National Health Service in England. We demonstrated a significantly better response in the patient cohort treated with dose titration than with age-based stimulus dosing. Peak doses were less and the total cumulative dose was less in the dose titration group than in the age-based stimulus dosing group. Our findings are consistent with superior outcomes in patients treated using a dose titration protocol when compared with age-based stimulus dosing in a similar cohort of patients.

Manual versus Automated Rodent Behavioral Assessment: Comparing Efficacy and Ease of Bederson and Garcia Neurological Deficit Scores to an Open Field Video-Tracking System.

PubMed

Desland, Fiona A; Afzal, Aqeela; Warraich, Zuha; Mocco, J

2014-01-01

Animal models of stroke have been crucial in advancing our understanding of the pathophysiology of cerebral ischemia. Currently, the standards for determining neurological deficit in rodents are the Bederson and Garcia scales, manual assessments scoring animals based on parameters ranked on a narrow scale of severity. Automated open field analysis of a live-video tracking system that analyzes animal behavior may provide a more sensitive test. Results obtained from the manual Bederson and Garcia scales did not show significant differences between pre- and post-stroke animals in a small cohort. When using the same cohort, however, post-stroke data obtained from automated open field analysis showed significant differences in several parameters. Furthermore, large cohort analysis also demonstrated increased sensitivity with automated open field analysis versus the Bederson and Garcia scales. These early data indicate use of automated open field analysis software may provide a more sensitive assessment when compared to traditional Bederson and Garcia scales.

A Comparison of Different Methods for Evaluating Diet, Physical Activity, and Long-Term Weight Gain in 3 Prospective Cohort Studies123

PubMed Central

Smith, Jessica D; Hou, Tao; Hu, Frank B; Rimm, Eric B; Spiegelman, Donna; Willett, Walter C; Mozaffarian, Dariush

2015-01-01

Background: The insidious pace of long-term weight gain (∼1 lb/y or 0.45 kg/y) makes it difficult to study in trials; long-term prospective cohorts provide crucial evidence on its key contributors. Most previous studies have evaluated how prevalent lifestyle habits relate to future weight gain rather than to lifestyle changes, which may be more temporally and physiologically relevant. Objective: Our objective was to evaluate and compare different methodological approaches for investigating diet, physical activity (PA), and long-term weight gain. Methods: In 3 prospective cohorts (total n = 117,992), we assessed how lifestyle relates to long-term weight change (up to 24 y of follow-up) in 4-y periods by comparing 3 analytic approaches: 1) prevalent diet and PA and 4-y weight change (prevalent analysis); 2) 4-y changes in diet and PA with a 4-y weight change (change analysis); and 3) 4-y change in diet and PA with weight change in the subsequent 4 y (lagged-change analysis). We compared these approaches and evaluated the consistency across cohorts, magnitudes of associations, and biological plausibility of findings. Results: Across the 3 methods, consistent, robust, and biologically plausible associations were seen only for the change analysis. Results for prevalent or lagged-change analyses were less consistent across cohorts, smaller in magnitude, and biologically implausible. For example, for each serving of a sugar-sweetened beverage, the observed weight gain was 0.01 lb (95% CI: −0.08, 0.10) [0.005 kg (95% CI: −0.04, 0.05)] based on prevalent analysis; 0.99 lb (95% CI: 0.83, 1.16) [0.45 kg (95% CI: 0.38, 0.53)] based on change analysis; and 0.05 lb (95% CI: −0.10, 0.21) [0.02 kg (95% CI: −0.05, 0.10)] based on lagged-change analysis. Findings were similar for other foods and PA. Conclusions: Robust, consistent, and biologically plausible relations between lifestyle and long-term weight gain are seen when evaluating lifestyle changes and weight changes in discrete periods rather than in prevalent lifestyle or lagged changes. These findings inform the optimal methods for evaluating lifestyle and long-term weight gain and the potential for bias when other methods are used. PMID:26377763

A Comparison of Different Methods for Evaluating Diet, Physical Activity, and Long-Term Weight Gain in 3 Prospective Cohort Studies.

PubMed

Smith, Jessica D; Hou, Tao; Hu, Frank B; Rimm, Eric B; Spiegelman, Donna; Willett, Walter C; Mozaffarian, Dariush

2015-11-01

The insidious pace of long-term weight gain (∼ 1 lb/y or 0.45 kg/y) makes it difficult to study in trials; long-term prospective cohorts provide crucial evidence on its key contributors. Most previous studies have evaluated how prevalent lifestyle habits relate to future weight gain rather than to lifestyle changes, which may be more temporally and physiologically relevant. Our objective was to evaluate and compare different methodological approaches for investigating diet, physical activity (PA), and long-term weight gain. In 3 prospective cohorts (total n = 117,992), we assessed how lifestyle relates to long-term weight change (up to 24 y of follow-up) in 4-y periods by comparing 3 analytic approaches: 1) prevalent diet and PA and 4-y weight change (prevalent analysis); 2) 4-y changes in diet and PA with a 4-y weight change (change analysis); and 3) 4-y change in diet and PA with weight change in the subsequent 4 y (lagged-change analysis). We compared these approaches and evaluated the consistency across cohorts, magnitudes of associations, and biological plausibility of findings. Across the 3 methods, consistent, robust, and biologically plausible associations were seen only for the change analysis. Results for prevalent or lagged-change analyses were less consistent across cohorts, smaller in magnitude, and biologically implausible. For example, for each serving of a sugar-sweetened beverage, the observed weight gain was 0.01 lb (95% CI: -0.08, 0.10) [0.005 kg (95% CI: -0.04, 0.05)] based on prevalent analysis; 0.99 lb (95% CI: 0.83, 1.16) [0.45 kg (95% CI: 0.38, 0.53)] based on change analysis; and 0.05 lb (95% CI: -0.10, 0.21) [0.02 kg (95% CI: -0.05, 0.10)] based on lagged-change analysis. Findings were similar for other foods and PA. Robust, consistent, and biologically plausible relations between lifestyle and long-term weight gain are seen when evaluating lifestyle changes and weight changes in discrete periods rather than in prevalent lifestyle or lagged changes. These findings inform the optimal methods for evaluating lifestyle and long-term weight gain and the potential for bias when other methods are used. © 2015 American Society for Nutrition.

Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhao, Jianhua; Zeng, Haishan; Kalia, Sunil; Lui, Harvey

2017-02-01

Background: Raman spectroscopy is a non-invasive optical technique which can measure molecular vibrational modes within tissue. A large-scale clinical study (n = 518) has demonstrated that real-time Raman spectroscopy could distinguish malignant from benign skin lesions with good diagnostic accuracy; this was validated by a follow-up independent study (n = 127). Objective: Most of the previous diagnostic algorithms have typically been based on analyzing the full band of the Raman spectra, either in the fingerprint or high wavenumber regions. Our objective in this presentation is to explore wavenumber selection based analysis in Raman spectroscopy for skin cancer diagnosis. Methods: A wavenumber selection algorithm was implemented using variably-sized wavenumber windows, which were determined by the correlation coefficient between wavenumbers. Wavenumber windows were chosen based on accumulated frequency from leave-one-out cross-validated stepwise regression or least and shrinkage selection operator (LASSO). The diagnostic algorithms were then generated from the selected wavenumber windows using multivariate statistical analyses, including principal component and general discriminant analysis (PC-GDA) and partial least squares (PLS). A total cohort of 645 confirmed lesions from 573 patients encompassing skin cancers, precancers and benign skin lesions were included. Lesion measurements were divided into training cohort (n = 518) and testing cohort (n = 127) according to the measurement time. Result: The area under the receiver operating characteristic curve (ROC) improved from 0.861-0.891 to 0.891-0.911 and the diagnostic specificity for sensitivity levels of 0.99-0.90 increased respectively from 0.17-0.65 to 0.20-0.75 by selecting specific wavenumber windows for analysis. Conclusion: Wavenumber selection based analysis in Raman spectroscopy improves skin cancer diagnostic specificity at high sensitivity levels.

Incidence of cancer and overall risk of mortality in individuals treated with raltegravir-based and non-raltegravir-based combination antiretroviral therapy regimens.

PubMed

Cozzi-Lepri, A; Zangerle, R; Machala, L; Zilmer, K; Ristola, M; Pradier, C; Kirk, O; Sambatakou, H; Fätkenheuer, G; Yust, I; Schmid, P; Gottfredsson, M; Khromova, I; Jilich, D; Flisiak, R; Smidt, J; Rozentale, B; Radoi, R; Losso, M H; Lundgren, J D; Mocroft, A

2018-02-01

There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95-1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37-2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84-1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90-1.61) and 0.83 (95% CI 0.70-0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47-1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65-1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53-1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76-1.72 for RALvs. CONC). We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups. © 2017 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

Decision curve analysis and external validation of the postoperative Karakiewicz nomogram for renal cell carcinoma based on a large single-center study cohort.

PubMed

Zastrow, Stefan; Brookman-May, Sabine; Cong, Thi Anh Phuong; Jurk, Stanislaw; von Bar, Immanuel; Novotny, Vladimir; Wirth, Manfred

2015-03-01

To predict outcome of patients with renal cell carcinoma (RCC) who undergo surgical therapy, risk models and nomograms are valuable tools. External validation on independent datasets is crucial for evaluating accuracy and generalizability of these models. The objective of the present study was to externally validate the postoperative nomogram developed by Karakiewicz et al. for prediction of cancer-specific survival. A total of 1,480 consecutive patients with a median follow-up of 82 months (IQR 46-128) were included into this analysis with 268 RCC-specific deaths. Nomogram-estimated survival probabilities were compared with survival probabilities of the actual cohort, and concordance indices were calculated. Calibration plots and decision curve analyses were used for evaluating calibration and clinical net benefit of the nomogram. Concordance between predictions of the nomogram and survival rates of the cohort was 0.911 after 12, 0.909 after 24 months and 0.896 after 60 months. Comparison of predicted probabilities and actual survival estimates with calibration plots showed an overestimation of tumor-specific survival based on nomogram predictions of high-risk patients, although calibration plots showed a reasonable calibration for probability ranges of interest. Decision curve analysis showed a positive net benefit of nomogram predictions for our patient cohort. The postoperative Karakiewicz nomogram provides a good concordance in this external cohort and is reasonably calibrated. It may overestimate tumor-specific survival in high-risk patients, which should be kept in mind when counseling patients. A positive net benefit of nomogram predictions was proven.

Impact of aging on host immune response and survival in melanoma: an analysis of 3 patient cohorts.

PubMed

Weiss, Sarah A; Han, Joseph; Darvishian, Farbod; Tchack, Jeremy; Han, Sung Won; Malecek, Karolina; Krogsgaard, Michelle; Osman, Iman; Zhong, Judy

2016-10-19

Age has been reported as an independent prognostic factor for melanoma-specific survival (MSS). We tested the hypothesis that age impacts the host anti-tumor immune response, accounting for age-specific survival outcomes in three unique melanoma patient cohorts. We queried the U.S. population-based Surveillance, Epidemiology, and End Results Program (SEER), the prospective tertiary care hospital-based Interdisciplinary Melanoma Cooperative Group (IMCG) biorepository, and the Cancer Genome Atlas (TCGA) biospecimen database to test the association of patient age at time of melanoma diagnosis with clinicopathologic features and survival outcomes. Age groups were defined as ≤45 (young), 46-65 (intermediate), and >65 (older). Each age group in the IMCG and TCGA cohorts was stratified by tumor infiltrating lymphocyte (TIL) measurements and tested for association with MSS. Differential expression of 594 immunoregulatory genes was assessed in a subset of primary melanomas in the IMCG and TCGA cohorts using an integrative pathway analysis. We analyzed 304, 476 (SEER), 1241 (IMCG), and 292 (TCGA) patients. Increasing age at melanoma diagnosis in both the SEER and IMCG cohorts demonstrated a positive correlation with tumor thickness, ulceration, stage, and mortality, however age in the TCGA cohort did not correlate with mortality. Older age was associated with shorter MSS in all three cohorts. When the young age group in both the IMCG and TCGA cohorts was stratified by TIL status, there were no differences in MSS. However, older IMCG patients with brisk TILs and intermediate aged TCGA patients with high lymphocyte scores (3-6) had improved MSS. Gene expression analysis revealed top pathways (T cell trafficking, communication, and differentiation) and top upstream regulators (CD3, CD28, IFNG, and STAT3) that significantly changed with age in 84 IMCG and 43 TCGA primary melanomas. Older age at time of melanoma diagnosis is associated with shorter MSS, however age's association with clinicopathologic features is dependent upon specific characteristics of the study population. TIL as a read-out of the host immune response may have greater prognostic impact in patients older than age 45. Recognition of age-related factors negatively impacting host immune responses may provide new insights into therapeutic strategies for the elderly.

Vitamin B6 Intake and the Risk of Colorectal Cancer: A Meta-Analysis of Prospective Cohort Studies.

PubMed

Jia, Kai; Wang, Rong; Tian, Jingfeng

2017-07-01

We performed this meta-analysis to estimate the association between vitamin B 6 intake and colorectal cancer risk. Prospective cohort studies on vitamin B 6 intake and colorectal cancer risk were identified by searching databases from the period of 1960 to 2016. Results from individual studies were synthetically combined using Stata 13.0 software. A total of 10 prospective cohort studies including 13 data sets were included in our meta-analysis, containing 7,817 cases and 784,550 subjects. The combined relative risks (RR) of colorectal cancer for the highest vitamin B 6 intake compared with the lowest vitamin B 6 intake was 0.88 [95% confidence intervals (CIs): 0.77-1.02]. Dose-response meta-analysis based on five eligible studies showed that for each additional 3 and 5 mg of vitamin B 6 intake, the risk would decrease by 11% (RR: 0.89, 95%CI: 0.81-0.98) and 17% (RR: 0.83, 95%CI: 0.71-0.97), respectively. Little evidence of publication bias was found. This meta-analysis provides evidence of a nonsignificant decrease in colorectal cancer risk associated with the high level of vitamin B 6 intake, but the risk in dose-response analysis is significant. However, the latter finding is based on a limited number of studies, which should be interpreted with caution.

Meta-GWAS and Meta-Analysis of Exome Array Studies Do Not Reveal Genetic Determinants of Serum Hepcidin

PubMed Central

Galesloot, Tessel E.; van Dijk, Freerk; Geurts-Moespot, Anneke J.; Girelli, Domenico; Kiemeney, Lambertus A. L. M.; Sweep, Fred C. G. J.; Swertz, Morris A.; van der Meer, Peter; Camaschella, Clara; Toniolo, Daniela; Vermeulen, Sita H.; van der Harst, Pim; Swinkels, Dorine W.

2016-01-01

Serum hepcidin concentration is regulated by iron status, inflammation, erythropoiesis and numerous other factors, but underlying processes are incompletely understood. We studied the association of common and rare single nucleotide variants (SNVs) with serum hepcidin in one Italian study and two large Dutch population-based studies. We genotyped common SNVs with genome-wide association study (GWAS) arrays and subsequently performed imputation using the 1000 Genomes reference panel. Cohort-specific GWAS were performed for log-transformed serum hepcidin, adjusted for age and gender, and results were combined in a fixed-effects meta-analysis (total N 6,096). Six top SNVs (p<5x10-6) were genotyped in 3,821 additional samples, but associations were not replicated. Furthermore, we meta-analyzed cohort-specific exome array association results of rare SNVs with serum hepcidin that were available for two of the three cohorts (total N 3,226), but no exome-wide significant signal (p<1.4x10-6) was identified. Gene-based meta-analyses revealed 19 genes that showed significant association with hepcidin. Our results suggest the absence of common SNVs and rare exonic SNVs explaining a large proportion of phenotypic variation in serum hepcidin. We recommend extension of our study once additional substantial cohorts with hepcidin measurements, GWAS and/or exome array data become available in order to increase power to identify variants that explain a smaller proportion of hepcidin variation. In addition, we encourage follow-up of the potentially interesting genes that resulted from the gene-based analysis of low-frequency and rare variants. PMID:27846281

Shift work, night work, and the risk of prostate cancer: A meta-analysis based on 9 cohort studies.

PubMed

Du, Hong-Bing; Bin, Kai-Yun; Liu, Wen-Hong; Yang, Feng-Sheng

2017-11-01

Epidemiology studies suggested that shift work or night work may be linked to prostate cancer (PCa); the relationship, however, remains controversy. PubMed, ScienceDirect, and Embase (Ovid) databases were searched before (started from the building of the databases) February 4, 2017 for eligible cohort studies. We pooled the evidence included by a random- or fixed-effect model, according to the heterogeneity. A predefined subgroup analysis was conducted to see the potential discrepancy between groups. Sensitivity analysis was used to test whether our results were stale. Nine cohort studies were eligible for meta-analysis with 2,570,790 male subjects. Our meta-analysis showed that, under the fixed-effect model, the pooled relevant risk (RR) of PCa was 1.05 (95% confidence interval [CI]: 1.00, 1.11; P = .06; I = 24.00%) for men who had ever engaged in night shift work; and under the random-effect model, the pooled RR was 1.08 (0.99, 1.17; P = .08; I = 24.00%). Subgroup analysis showed the RR of PCa among males in western countries was 1.05 (95% CI: 0.99, 1.11; P = .09; I = 0.00%), while among Asian countries it was 2.45 (95% CI: 1.19, 5.04; P = .02; I = 0.00%); and the RR was 1.04 (95% CI: 0.95, 1.14; P = .40; I = 29.20%) for the high-quality group compared with 1.21 (95% CI: 1.03, 1.41; P = .02; I = 0.00%) for the moderate/low-quality group. Sensitivity analysis showed robust results. Based on the current evidence of cohort studies, we found no obvious association between night shift work and PCa. However, our subgroup analysis suggests that night shift work may increase the risk of PCa in Asian men. Some evidence of a small study effect was observed in this meta-analysis.

Predicting Blunt Cerebrovascular Injury in Pediatric Trauma: Validation of the “Utah Score”

PubMed Central

Ravindra, Vijay M.; Bollo, Robert J.; Sivakumar, Walavan; Akbari, Hassan; Naftel, Robert P.; Limbrick, David D.; Jea, Andrew; Gannon, Stephen; Shannon, Chevis; Birkas, Yekaterina; Yang, George L.; Prather, Colin T.; Kestle, John R.

2017-01-01

Abstract Risk factors for blunt cerebrovascular injury (BCVI) may differ between children and adults, suggesting that children at low risk for BCVI after trauma receive unnecessary computed tomography angiography (CTA) and high-dose radiation. We previously developed a score for predicting pediatric BCVI based on retrospective cohort analysis. Our objective is to externally validate this prediction score with a retrospective multi-institutional cohort. We included patients who underwent CTA for traumatic cranial injury at four pediatric Level I trauma centers. Each patient in the validation cohort was scored using the “Utah Score” and classified as high or low risk. Before analysis, we defined a misclassification rate <25% as validating the Utah Score. Six hundred forty-five patients (mean age 8.6 ± 5.4 years; 63.4% males) underwent screening for BCVI via CTA. The validation cohort was 411 patients from three sites compared with the training cohort of 234 patients. Twenty-two BCVIs (5.4%) were identified in the validation cohort. The Utah Score was significantly associated with BCVIs in the validation cohort (odds ratio 8.1 [3.3, 19.8], p < 0.001) and discriminated well in the validation cohort (area under the curve 72%). When the Utah Score was applied to the validation cohort, the sensitivity was 59%, specificity was 85%, positive predictive value was 18%, and negative predictive value was 97%. The Utah Score misclassified 16.6% of patients in the validation cohort. The Utah Score for predicting BCVI in pediatric trauma patients was validated with a low misclassification rate using a large, independent, multicenter cohort. Its implementation in the clinical setting may reduce the use of CTA in low-risk patients. PMID:27297774

A genome-wide association study of corneal astigmatism: The CREAM Consortium.

PubMed

Shah, Rupal L; Li, Qing; Zhao, Wanting; Tedja, Milly S; Tideman, J Willem L; Khawaja, Anthony P; Fan, Qiao; Yazar, Seyhan; Williams, Katie M; Verhoeven, Virginie J M; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J; Pärssinen, Olavi; Wedenoja, Juho; Biino, Ginevra; Concas, Maria Pina; Uitterlinden, André; Rivadeneira, Fernando; Jaddoe, Vincent W V; Hysi, Pirro G; Sim, Xueling; Tan, Nicholas; Tham, Yih-Chung; Sensaki, Sonoko; Hofman, Albert; Vingerling, Johannes R; Jonas, Jost B; Mitchell, Paul; Hammond, Christopher J; Höhn, René; Baird, Paul N; Wong, Tien-Yin; Cheng, Chinfsg-Yu; Teo, Yik Ying; Mackey, David A; Williams, Cathy; Saw, Seang-Mei; Klaver, Caroline C W; Guggenheim, Jeremy A; Bailey-Wilson, Joan E

2018-01-01

To identify genes and genetic markers associated with corneal astigmatism. A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha ( PDGFRA ) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08-1.16), p=5.55×10 -9 . No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans-claudin-7 ( CLDN7 ), acid phosphatase 2, lysosomal ( ACP2 ), and TNF alpha-induced protein 8 like 3 ( TNFAIP8L3 ). In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7 , ACP2 , and TNFAIP8L3 , that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism.

A Retrospective Administrative Database Analysis of Suicide Attempts and Completed Suicide in Patients With Chronic Pancreatitis.

PubMed

Chen, Chien-Hua; Lin, Cheng-Li; Hsu, Chung-Y; Kao, Chia-Hung

2018-01-01

Background: The actual incidence rate of suicide attempt and the suicide-related fatality rate (completed suicide) in patients with chronic pancreatitis (CP) have not been mentioned in the literature. Methods: We conducted a nationwide population-based cohort study by analyzing data from Taiwan's National Health Insurance Research Database (NHIRD) to compare the rate of suicide attempt between a CP cohort and a non-CP cohort. For the study cohort, we identified 17,733 patients (age ≥ 20 years) diagnosed as having CP between 2000 and 2010 from the NHIRD in Taiwan. Beneficiaries with no history of CP were matched with the study cohort at a 2:1 ratio according to age, sex, and index date. To determine the incidence of suicide, all patients were followed until the end of 2011 or until their withdrawal from the Taiwan National Health Insurance program. Results: Patients with CP had an increased risk of suicide attempt, compared with those without CP (adjusted hazard ratio [aHR] = 2.72, 95% confidence interval [CI] = 1.69-4.37). The suicide-related fatality in the CP cohort was higher than that in the non-CP cohort, but the difference was not statistically significant (aHR = 1.21, 95% CI = 0.39-3.78). Conclusion: Our population-based cohort study reveals a close association between CP and subsequent suicide attempt. Compared with the non-CP cohort, the suicide-related fatality was higher in the CP cohort, although the result was not statistically significant. These findings necessitate surveying patients with CP and providing psychological support to prevent suicide.

A Retrospective Administrative Database Analysis of Suicide Attempts and Completed Suicide in Patients With Chronic Pancreatitis

PubMed Central

Chen, Chien-Hua; Lin, Cheng-Li; Hsu, Chung-Y.; Kao, Chia-Hung

2018-01-01

Background: The actual incidence rate of suicide attempt and the suicide-related fatality rate (completed suicide) in patients with chronic pancreatitis (CP) have not been mentioned in the literature. Methods: We conducted a nationwide population-based cohort study by analyzing data from Taiwan's National Health Insurance Research Database (NHIRD) to compare the rate of suicide attempt between a CP cohort and a non-CP cohort. For the study cohort, we identified 17,733 patients (age ≥ 20 years) diagnosed as having CP between 2000 and 2010 from the NHIRD in Taiwan. Beneficiaries with no history of CP were matched with the study cohort at a 2:1 ratio according to age, sex, and index date. To determine the incidence of suicide, all patients were followed until the end of 2011 or until their withdrawal from the Taiwan National Health Insurance program. Results: Patients with CP had an increased risk of suicide attempt, compared with those without CP (adjusted hazard ratio [aHR] = 2.72, 95% confidence interval [CI] = 1.69–4.37). The suicide-related fatality in the CP cohort was higher than that in the non-CP cohort, but the difference was not statistically significant (aHR = 1.21, 95% CI = 0.39–3.78). Conclusion: Our population-based cohort study reveals a close association between CP and subsequent suicide attempt. Compared with the non-CP cohort, the suicide-related fatality was higher in the CP cohort, although the result was not statistically significant. These findings necessitate surveying patients with CP and providing psychological support to prevent suicide. PMID:29720951

Defining Multiple Chronic Conditions for Quality Measurement.

PubMed

Drye, Elizabeth E; Altaf, Faseeha K; Lipska, Kasia J; Spatz, Erica S; Montague, Julia A; Bao, Haikun; Parzynski, Craig S; Ross, Joseph S; Bernheim, Susannah M; Krumholz, Harlan M; Lin, Zhenqiu

2018-02-01

Patients with multiple chronic conditions (MCCs) are a critical but undefined group for quality measurement. We present a generally applicable systematic approach to defining an MCC cohort of Medicare fee-for-service beneficiaries that we developed for a national quality measure, risk-standardized rates of unplanned admissions for Accountable Care Organizations. To define the MCC cohort we: (1) identified potential chronic conditions; (2) set criteria for cohort conditions based on MCC framework and measure concept; (3) applied the criteria informed by empirical analysis, experts, and the public; (4) described "broader" and "narrower" cohorts; and (5) selected final cohort with stakeholder input. Subjects were patients with chronic conditions. Participants included 21.8 million Medicare fee-for-service beneficiaries in 2012 aged 65 years and above with ≥1 of 27 Medicare Chronic Condition Warehouse condition(s). In total, 10 chronic conditions were identified based on our criteria; 8 of these 10 were associated with notably increased admission risk when co-occurring. A broader cohort (2+ of the 8 conditions) included 4.9 million beneficiaries (23% of total cohort) with an admission rate of 70 per 100 person-years. It captured 53% of total admissions. The narrower cohort (3+ conditions) had 2.2 million beneficiaries (10%) with 100 admissions per 100 person-years and captured 32% of admissions. Most stakeholders viewed the broader cohort as best aligned with the measure concept. By systematically narrowing chronic conditions to those most relevant to the outcome and incorporating stakeholder input, we defined an MCC admission measure cohort supported by stakeholders. This approach can be used as a model for other MCC outcome measures.

Cost-effectiveness analysis of a system-based approach for managing neonatal jaundice and preventing kernicterus in Ontario.

PubMed

Xie, Bin; da Silva, Orlando; Zaric, Greg

2012-01-01

To evaluate the incremental cost-effectiveness of a system-based approach for the management of neonatal jaundice and the prevention of kernicterus in term and late-preterm (≥35 weeks) infants, compared with the traditional practice based on visual inspection and selected bilirubin testing. Two hypothetical cohorts of 150,000 term and late-preterm neonates were used to compare the costs and outcomes associated with the use of a system-based or traditional practice approach. Data for the evaluation were obtained from the case costing centre at a large teaching hospital in Ontario, supplemented by data from the literature. The per child cost for the system-based approach cohort was $176, compared with $173 in the traditional practice cohort. The higher cost associated with the system-based cohort reflects increased costs for predischarge screening and treatment and increased postdischarge follow-up visits. These costs are partially offset by reduced costs from fewer emergency room visits, hospital readmissions and kernicterus cases. Compared with the traditional approach, the cost to prevent one kernicterus case using the system-based approach was $570,496, the cost per life year gained was $26,279, and the cost per quality-adjusted life year gained was $65,698. The cost to prevent one kernicterus case using the system-based approach is much lower than previously reported in the literature.

Cost-effectiveness analysis of a system-based approach for managing neonatal jaundice and preventing kernicterus in Ontario

PubMed Central

Xie, Bin; da Silva, Orlando; Zaric, Greg

2012-01-01

OBJECTIVE: To evaluate the incremental cost-effectiveness of a system-based approach for the management of neonatal jaundice and the prevention of kernicterus in term and late-preterm (≥35 weeks) infants, compared with the traditional practice based on visual inspection and selected bilirubin testing. STUDY DESIGN: Two hypothetical cohorts of 150,000 term and late-preterm neonates were used to compare the costs and outcomes associated with the use of a system-based or traditional practice approach. Data for the evaluation were obtained from the case costing centre at a large teaching hospital in Ontario, supplemented by data from the literature. RESULTS: The per child cost for the system-based approach cohort was $176, compared with $173 in the traditional practice cohort. The higher cost associated with the system-based cohort reflects increased costs for predischarge screening and treatment and increased postdischarge follow-up visits. These costs are partially offset by reduced costs from fewer emergency room visits, hospital readmissions and kernicterus cases. Compared with the traditional approach, the cost to prevent one kernicterus case using the system-based approach was $570,496, the cost per life year gained was $26,279, and the cost per quality-adjusted life year gained was $65,698. CONCLUSION: The cost to prevent one kernicterus case using the system-based approach is much lower than previously reported in the literature. PMID:23277747

A microRNA-based prediction model for lymph node metastasis in hepatocellular carcinoma.

PubMed

Zhang, Li; Xiang, Zuo-Lin; Zeng, Zhao-Chong; Fan, Jia; Tang, Zhao-You; Zhao, Xiao-Mei

2016-01-19

We developed an efficient microRNA (miRNA) model that could predict the risk of lymph node metastasis (LNM) in hepatocellular carcinoma (HCC). We first evaluated a training cohort of 192 HCC patients after hepatectomy and found five LNM associated predictive factors: vascular invasion, Barcelona Clinic Liver Cancer stage, miR-145, miR-31, and miR-92a. The five statistically independent factors were used to develop a predictive model. The predictive value of the miRNA-based model was confirmed in a validation cohort of 209 consecutive HCC patients. The prediction model was scored for LNM risk from 0 to 8. The cutoff value 4 was used to distinguish high-risk and low-risk groups. The model sensitivity and specificity was 69.6 and 80.2%, respectively, during 5 years in the validation cohort. And the area under the curve (AUC) for the miRNA-based prognostic model was 0.860. The 5-year positive and negative predictive values of the model in the validation cohort were 30.3 and 95.5%, respectively. Cox regression analysis revealed that the LNM hazard ratio of the high-risk versus low-risk groups was 11.751 (95% CI, 5.110-27.021; P < 0.001) in the validation cohort. In conclusion, the miRNA-based model is reliable and accurate for the early prediction of LNM in patients with HCC.

Investigating the impact of a research-based integrated curriculum on self-perceived research experiences of medical students in community placements: a pre- and post-test analysis of three student cohorts.

PubMed

Mullan, Judy R; Weston, Kathryn M; Rich, Warren C; McLennan, Peter L

2014-08-05

To build research capacity among graduating medical students, the teaching of research and critical analysis was integrated into the University of Wollongong (UoW) new, graduate-entry medical curriculum. This study examined whether the self-perceived research experiences of medical students, and consequent research capability, were influenced by exposure to this innovative research and critical analysis curriculum, which incorporated a 12-month community-based research project, and associated assessment tasks. The first three medical students cohorts (N = 221) completed a self-assessment of their research experiences in ten areas of research activity. Their responses were collected: before and after they undertook an individual community-based research project within a 12-month regional/rural clinical placement. The research areas investigated by the self-assessment tool were: (i) defining a research question/idea; (ii) writing a research protocol; (iii) finding relevant literature; (iv) critically reviewing the literature; (v) using quantitative research methods; (vi) using qualitative research methods; (vii) analysing and interpreting results; (viii) writing and presenting a research report; (ix) publishing results; and (x) applying for research funding. Participation rates of 94% (207/221) pre-placement and 99% (219/221) post-placement were achieved from the three student cohorts. Following the successful completion of the research projects and their assessment tasks, the median responses were significantly higher (p < 0.05) in nine of the ten research areas. The only area of research for which there was no increase recorded for any one of the three cohorts, or overall, was (x) applying for research funding. This activity was not a component of the UoW research and critical analysis curriculum and the item was included as a test of internal validity. Significant gains were also seen between cohorts in some key research areas. Improved research capability among medical students was evidenced by increased scores in various areas of research experience in the context of successful completion of relevant assessment tasks. The results suggest that research capability of medical students can be positively influenced by the provision of a research-based integrated medical curriculum and further consolidated by authentic learning experiences, gained through conducting 'hands-on' research projects, under the supervision and mentoring of research-qualified academics.

Investigating the impact of a research-based integrated curriculum on self-perceived research experiences of medical students in community placements: a pre- and post-test analysis of three student cohorts

PubMed Central

2014-01-01

Background To build research capacity among graduating medical students, the teaching of research and critical analysis was integrated into the University of Wollongong (UoW) new, graduate-entry medical curriculum. This study examined whether the self-perceived research experiences of medical students, and consequent research capability, were influenced by exposure to this innovative research and critical analysis curriculum, which incorporated a 12-month community-based research project, and associated assessment tasks. Methods The first three medical students cohorts (N = 221) completed a self-assessment of their research experiences in ten areas of research activity. Their responses were collected: before and after they undertook an individual community-based research project within a 12-month regional/rural clinical placement. The research areas investigated by the self-assessment tool were: (i) defining a research question/idea; (ii) writing a research protocol; (iii) finding relevant literature; (iv) critically reviewing the literature; (v) using quantitative research methods; (vi) using qualitative research methods; (vii) analysing and interpreting results; (viii) writing and presenting a research report; (ix) publishing results; and (x) applying for research funding. Results Participation rates of 94% (207/221) pre-placement and 99% (219/221) post-placement were achieved from the three student cohorts. Following the successful completion of the research projects and their assessment tasks, the median responses were significantly higher (p < 0.05) in nine of the ten research areas. The only area of research for which there was no increase recorded for any one of the three cohorts, or overall, was (x) applying for research funding. This activity was not a component of the UoW research and critical analysis curriculum and the item was included as a test of internal validity. Significant gains were also seen between cohorts in some key research areas. Conclusions Improved research capability among medical students was evidenced by increased scores in various areas of research experience in the context of successful completion of relevant assessment tasks. The results suggest that research capability of medical students can be positively influenced by the provision of a research-based integrated medical curriculum and further consolidated by authentic learning experiences, gained through conducting ‘hands-on’ research projects, under the supervision and mentoring of research-qualified academics. PMID:25096817

History of having a macrosomic infant and the risk of diabetes: the Japan public health center-based prospective diabetes study.

PubMed

Kabeya, Yusuke; Goto, Atsushi; Kato, Masayuki; Takahashi, Yoshihiko; Matsushita, Yumi; Inoue, Manami; Mizoue, Tetsuya; Tsugane, Shoichiro; Kadowaki, Takashi; Noda, Mitsuhiko

2013-01-01

The aim of the present study was to test a hypothesis that a history of having a macrosomic infant (≥ 4000 g) is associated with the risk of diabetes. Data on the Japan Public Health Center-based Prospective diabetes cohort were analyzed, which is a population-based cohort study on diabetes. The survey of diabetes was performed at baseline and at the 5-year follow-up. A history of having a macrosomic infant was assessed using a self-administered questionnaire. A cross-sectional analysis was performed among 12,153 women who participated in the 5-year survey of the cohort. Logistic regression was used to examine the relationship between a history of having a macrosomic infant and the presence of diabetes. A longitudinal analysis was also conducted among 7,300 women without diabetes who participated in the baseline survey. Logistic regression was used to investigate the relationship between a history of having a macrosomic infant and the incidence of diabetes between the baseline survey and the 5-year survey. In the cross-sectional analysis, parous women with a positive history were more likely to have diabetes in relation to parous women without (OR = 1.44, 95% CI = 1.13-1.83). The longitudinal analysis showed a modest but non-significant increased risk of developing diabetes among women with a positive history (OR = 1.24, 95% CI = 0.80-1.94). An increased risk of diabetes was implied among women with a history of having a macrosomic infant although the longitudinal analysis showed a non-significant increased risk.

Is beryllium-induced lung cancer caused only by soluble forms and high exposure levels?

PubMed

Schubauer-Berigan, Mary K; Couch, James R; Deddens, James A

2017-08-01

The US Occupational Safety and Health Administration (OSHA) recently proposed a permissible exposure limit of 0.2 µg/m 3 for beryllium, based partly on extrapolated estimates of lung cancer risk from a pooled occupational cohort. The purpose of the present analysis was to evaluate whether cohort members exposed at lower levels to mainly insoluble forms of beryllium exhibit increased risk of lung cancer. We conducted Cox proportional hazards regression analyses among 75 lung cancer cases in age-based risk sets within two lower exposure plants in the pooled cohort followed from 1940 to 2005. We used categorical and power models to evaluate exposure-response patterns for mean and cumulative beryllium exposures in the two-plant cohort, comparing findings with the full pooled cohort. We also evaluated the distribution of exposure-years in each cohort by solubility class (soluble, insoluble and mixed). 98% of workers in the two-plant cohort were hired between 1955 and 1969. The mean beryllium exposure averaged 1.3 µg/m 3 and the predominant form was insoluble. Adjusting for confounders, we observed a monotonic increase in lung cancer mortality across exposure categories in the two-plant cohort. The exposure-response coefficients (per unit ln exposure) were 0.270 (p=0.061) for mean exposure and 0.170 (p=0.033) for cumulative exposure, compared with 0.155 and 0.094 (respectively) in the full cohort. The low-exposure levels at these two plants and the predominance of insoluble beryllium suggest that the overall pooled cohort findings on which OSHA's lung cancer risk assessment is based are relevant for current workers exposed to any form of beryllium. © 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.

A GWAS meta-analysis from 5 population-based cohorts implicates ion channel genes in the pathogenesis of irritable bowel syndrome.

PubMed

Bonfiglio, F; Henström, M; Nag, A; Hadizadeh, F; Zheng, T; Cenit, M C; Tigchelaar, E; Williams, F; Reznichenko, A; Ek, W E; Rivera, N V; Homuth, G; Aghdassi, A A; Kacprowski, T; Männikkö, M; Karhunen, V; Bujanda, L; Rafter, J; Wijmenga, C; Ronkainen, J; Hysi, P; Zhernakova, A; D'Amato, M

2018-04-19

Irritable bowel syndrome (IBS) shows genetic predisposition, however, large-scale, powered gene mapping studies are lacking. We sought to exploit existing genetic (genotype) and epidemiological (questionnaire) data from a series of population-based cohorts for IBS genome-wide association studies (GWAS) and their meta-analysis. Based on questionnaire data compatible with Rome III Criteria, we identified a total of 1335 IBS cases and 9768 asymptomatic individuals from 5 independent European genotyped cohorts. Individual GWAS were carried out with sex-adjusted logistic regression under an additive model, followed by meta-analysis using the inverse variance method. Functional annotation of significant results was obtained via a computational pipeline exploiting ontology and interaction networks, and tissue-specific and gene set enrichment analyses. Suggestive GWAS signals (P ≤ 5.0 × 10 -6 ) were detected for 7 genomic regions, harboring 64 gene candidates to affect IBS risk via functional or expression changes. Functional annotation of this gene set convincingly (best FDR-corrected P = 3.1 × 10 -10 ) highlighted regulation of ion channel activity as the most plausible pathway affecting IBS risk. Our results confirm the feasibility of population-based studies for gene-discovery efforts in IBS, identify risk genes and loci to be prioritized in independent follow-ups, and pinpoint ion channels as important players and potential therapeutic targets warranting further investigation. © 2018 John Wiley & Sons Ltd.

Influence of exposure assessment and parameterization on exposure response. Aspects of epidemiologic cohort analysis using the Libby Amphibole asbestos worker cohort.

PubMed

Bateson, Thomas F; Kopylev, Leonid

2015-01-01

Recent meta-analyses of occupational epidemiology studies identified two important exposure data quality factors in predicting summary effect measures for asbestos-associated lung cancer mortality risk: sufficiency of job history data and percent coverage of work history by measured exposures. The objective was to evaluate different exposure parameterizations suggested in the asbestos literature using the Libby, MT asbestos worker cohort and to evaluate influences of exposure measurement error caused by historically estimated exposure data on lung cancer risks. Focusing on workers hired after 1959, when job histories were well-known and occupational exposures were predominantly based on measured exposures (85% coverage), we found that cumulative exposure alone, and with allowance of exponential decay, fit lung cancer mortality data similarly. Residence-time-weighted metrics did not fit well. Compared with previous analyses based on the whole cohort of Libby workers hired after 1935, when job histories were less well-known and exposures less frequently measured (47% coverage), our analyses based on higher quality exposure data yielded an effect size as much as 3.6 times higher. Future occupational cohort studies should continue to refine retrospective exposure assessment methods, consider multiple exposure metrics, and explore new methods of maintaining statistical power while minimizing exposure measurement error.

COVARIATE-ADAPTIVE CLUSTERING OF EXPOSURES FOR AIR POLLUTION EPIDEMIOLOGY COHORTS*

PubMed Central

Keller, Joshua P.; Drton, Mathias; Larson, Timothy; Kaufman, Joel D.; Sandler, Dale P.; Szpiro, Adam A.

2017-01-01

Cohort studies in air pollution epidemiology aim to establish associations between health outcomes and air pollution exposures. Statistical analysis of such associations is complicated by the multivariate nature of the pollutant exposure data as well as the spatial misalignment that arises from the fact that exposure data are collected at regulatory monitoring network locations distinct from cohort locations. We present a novel clustering approach for addressing this challenge. Specifically, we present a method that uses geographic covariate information to cluster multi-pollutant observations and predict cluster membership at cohort locations. Our predictive k-means procedure identifies centers using a mixture model and is followed by multi-class spatial prediction. In simulations, we demonstrate that predictive k-means can reduce misclassification error by over 50% compared to ordinary k-means, with minimal loss in cluster representativeness. The improved prediction accuracy results in large gains of 30% or more in power for detecting effect modification by cluster in a simulated health analysis. In an analysis of the NIEHS Sister Study cohort using predictive k-means, we find that the association between systolic blood pressure (SBP) and long-term fine particulate matter (PM2.5) exposure varies significantly between different clusters of PM2.5 component profiles. Our cluster-based analysis shows that for subjects assigned to a cluster located in the Midwestern U.S., a 10 μg/m3 difference in exposure is associated with 4.37 mmHg (95% CI, 2.38, 6.35) higher SBP. PMID:28572869

Do occupational exposures to vinyl chloride cause hepatocellular carcinoma and cirrhosis?

PubMed

Lotti, Marcello

2017-05-01

Controversy exists about the association between occupational exposures to vinyl chloride and hepatocellular carcinoma and cirrhosis. Two large multicentre mortality cohort studies, one American and another European, reported higher mortality for primary cancer of liver and biliary tract. However, the American study was not able to rule out misclassification, because based on death certificates and under the heading primary liver cancers, some angiosarcomas, the typical neoplasia associated with vinyl chloride, may have been included. The American study does not report on cirrhosis mortality. The European study also reports higher mortality of primary liver cancer, but contrary to the American study in a further analysis based on 10 verified cases of hepatocellular carcinoma, an exposure-response trend with duration of employment and with cumulative exposure to vinyl chloride was detected. A smaller cohort belonging to this multicentre cohort confirmed these results. Meta-analyses based on the two large cohorts concluded for a small excess of primary liver cancer, although misclassification could not be ruled out. Excess risk of cirrhosis was reported in the European cohort, in a subcohort and in a cross-sectional study. However, a meta-analysis did not confirm this excess. Several critical appraisals of the literature reached antithetical conclusions about hepatocellular carcinoma, cirrhosis and occupational exposures to vinyl chloride. For both hepatocellular carcinoma and cirrhosis, a study suggests an additive and multiplicative effect of vinyl chloride exposure with viral hepatitis and alcohol consumption respectively. Pathology reports seem to indicate a possible development of hepatocellular carcinoma but not of cirrhosis after high exposures to vinyl chloride. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risk factors for cardiomyopathy syndrome (CMS) in Norwegian salmon farming.

PubMed

Bang Jensen, Britt; Brun, Edgar; Fineid, Birgitte; Larssen, Rolf Bjerke; Kristoffersen, Anja B

2013-12-12

Cardiomyopathy syndrome (CMS) has been an economically important disease in Norwegian aquaculture since the 1990s. In this study, data on monthly production characteristics and case registrations were combined in a cohort study and supplemented with a questionnaire-based case-control survey on management factors in order to identify risk factors for CMS. The cohort study included cases and controls from 2005 to 2012. From this dataset differences between all cases and controls were analyzed by a mixed effect multivariate logistic regression. From this we found that the probability of CMS increased with increasing time in the sea, infection pressure, and cohort size, and that cohorts which had previously been diagnosed with heart and skeletal muscle inflammation or which were in farms with a history of CMS in previous cohorts had double the odds of developing CMS. The model was then used to calculate the predicted value for each cohort from which additional data were obtained via the questionnaire-based survey and used as offset for calculating the probability of CMS in a semi-univariate analysis of additional risk factors. Finally, the model was used to calculate the probability of developing CMS in 100 different scenarios in which the cohorts were subject to increasingly worse conditions with regards to the risk factors from the dataset. We believe that this exercise is a good way of communicating the findings to farmers, so they can make informed decisions when trying to avoid CMS in their fish cohorts.

A Learner-led, Discussion-based Elective on Emerging Infectious Disease

PubMed Central

2015-01-01

Objective. To implement a learner-led, discussion-based course aimed at exposing second-year pharmacy learners to the study of emerging infectious diseases from a global health perspective and to assess the role and importance of pharmacists in the management of disease outbreaks. Design. Learners examined literature pertinent to an emerging infectious disease in a 3-credit, discussion-based course and participated in peer discussion led by a designated learner. Instructional materials included journal articles, audio-visual presentations, documentaries, book chapters, movies, newspaper/magazine articles, and other materials. Learning outcomes were measured based on the ability of learners to perform critical thinking and analysis, communicate with their peers, and participate in class discussions. Assessment. The course was offered to 2 consecutive cohorts consisting of 14 and 16 learners, respectively. Overall, every learner in the first cohort achieved a final grade of A for the course. In the second cohort, the overall grade distribution consisted of grades of A, B, and C for the course. Learner evaluations indicated that the active-learning, discussion-based environment significantly enhanced interest in the topic and overall performance in the course. Conclusion. The elective course on emerging infectious diseases provided in-depth exposure to disease topics normally not encountered in the pharmacy curriculum. Learners found the material and format valuable, and the course enhanced their appreciation of infectious diseases, research methodology, critical thinking and analysis, and their roles as pharmacists. PMID:26430268

A Learner-led, Discussion-based Elective on Emerging Infectious Disease.

PubMed

Mathias, Clinton

2015-08-25

Objective. To implement a learner-led, discussion-based course aimed at exposing second-year pharmacy learners to the study of emerging infectious diseases from a global health perspective and to assess the role and importance of pharmacists in the management of disease outbreaks. Design. Learners examined literature pertinent to an emerging infectious disease in a 3-credit, discussion-based course and participated in peer discussion led by a designated learner. Instructional materials included journal articles, audio-visual presentations, documentaries, book chapters, movies, newspaper/magazine articles, and other materials. Learning outcomes were measured based on the ability of learners to perform critical thinking and analysis, communicate with their peers, and participate in class discussions. Assessment. The course was offered to 2 consecutive cohorts consisting of 14 and 16 learners, respectively. Overall, every learner in the first cohort achieved a final grade of A for the course. In the second cohort, the overall grade distribution consisted of grades of A, B, and C for the course. Learner evaluations indicated that the active-learning, discussion-based environment significantly enhanced interest in the topic and overall performance in the course. Conclusion. The elective course on emerging infectious diseases provided in-depth exposure to disease topics normally not encountered in the pharmacy curriculum. Learners found the material and format valuable, and the course enhanced their appreciation of infectious diseases, research methodology, critical thinking and analysis, and their roles as pharmacists.

Survival and breeding advantages of larger Black Brant (Branta bernicla nigricans) goslings: Within- and among-cohort variation

USGS Publications Warehouse

Sedinger, J.S.; Chelgren, N.D.

2007-01-01

We examined the relationship between mass late in the first summer and survival and return to the natal breeding colony for 12 cohorts (1986-1997) of female Black Brant (Branta bernicla nigricans). We used Cormack-Jolly-Seber methods and the program MARK to analyze capture-recapture data. Models included two kinds of residuals from regressions of mass on days after peak of hatch when goslings were measured; one based on the entire sample (12 cohorts) and the other based only on individuals in the same cohort. Some models contained date of peak of hatch (a group covariate related to lateness of nesting in that year) and mean cohort residual mass. Finally, models allowed survival to vary among cohorts. The best model of encounter probability included an effect of residual mass on encounter probability and allowed encounter probability to vary among age classes and across years. All competitive models contained an effect of one of the estimates of residual mass; relatively larger goslings survived their first year at higher rates. Goslings in cohorts from later years in the analysis tended to have lower first-year survival, after controlling for residual mass, which reflected the generally smaller mean masses for these cohorts but was potentially also a result of population-density effects additional to those on growth. Variation among cohorts in mean mass accounted for 56% of variation among cohorts in first-year survival. Encounter probabilities, which were correlated with breeding probability, increased with relative mass, which suggests that larger goslings not only survived at higher rates but also bred at higher rates. Although our findings support the well-established linkage between gosling mass and fitness, they suggest that additional environmental factors also influence first-year survival.

Comparison of a CHOP-LAsp-based protocol with and without maintenance for canine multicentric lymphoma.

PubMed

Lautscham, E M; Kessler, M; Ernst, T; Willimzig, L; Neiger, R

2017-03-25

The recommendation to treat canine lymphoma with a discontinuous protocol is based on small case numbers and mostly historic controls. This study compares duration of first remission (DFR) and overall survival time (ST) with a discontinuous protocol to the same protocol with maintenance phase. 408 dogs were treated with a CHOP-LAsp (C=cyclophosphamide; H=hydroxydaunorubicin; O=Oncovin; P=prednisolone; LAsp=l-asparaginase)-based 28-week induction protocol. In 75 dogs (cohort 1), this was followed by a maintenance phase consisting of vincristine, chlorambucil and actinomycin-D with a total treatment duration of two years. In the subsequent 333 dogs, therapy was discontinued after induction (cohort 2). Median DFR and ST in cohort 1 were 216 and 375 days and 184 and 304 days in cohort 2. 6-Month, 1-year and 2-year survival rates in cohort 1 were 73 per cent, 50 per cent, 24 per cent and 67 per cent, 39 per cent, 21 per cent in cohort 2. There was no significant difference between the two protocols (P=0.291 for ST, P=0.071 for DFR). On multivariate analysis, corticosteroid pretreatment (P=0.005), thrombocytopenia at diagnosis (P=0.019), stage (P=0.009), substage b at relapse (P<0.001), age (P=0.002) and incomplete or unstable remission necessitating intensification of therapy (P=0.004) were negatively correlated with ST in both groups. This study supports the use of a discontinuous protocol for canine multicentric lymphoma. British Veterinary Association.

Longitudinal Commercial Claims–Based Cost Analysis of Diabetic Retinopathy Screening Patterns

PubMed Central

Fitch, Kathryn; Weisman, Thomas; Engel, Tyler; Turpcu, Adam; Blumen, Helen; Rajput, Yamina; Dave, Purav

2015-01-01

Background Diabetic retinopathy is one of the most common complications of diabetes. The screening of patients with diabetes to detect retinopathy is recommended by several professional guidelines but is an underutilized service. Objective To analyze the relationship between the frequency of retinopathy screening and the cost of care in adult patients with diabetes. Methods Truven Health MarketScan commercial databases (2000–2013) were used to identify the diabetic population aged 18 to 64 years for the performance of a 2001–2013 annual trend analysis of patients with type 1 and type 2 diabetes and a 10-year longitudinal analysis of patients with newly diagnosed type 2 diabetes. In the trend analysis, the prevalence of diabetes, screening rate, and allowed cost per member per month (PMPM) were calculated. In the longitudinal analysis, data from 4 index years (2001–2004) of patients newly diagnosed with type 2 diabetes were combined, and the costs were adjusted to be comparable to the 2004 index year cohort, using the annual diabetes population cost trends calculated in the trend analysis. The longitudinal population was segmented into the number of years of diabetic retinopathy screening (ie, 0, 1–4, 5–7, and 8–10), and the relationship between the years of screening and the PMPM allowed costs was analyzed. The difference in mean incremental cost between years 1 and 10 in each of the 4 cohorts was compared after adjusting for explanatory variables. Results In the trend analysis, between 2001 and 2013, the prevalence of diabetes increased from 3.93% to 5.08%, retinal screening increased from 26.27% to 29.58%, and the average total unadjusted allowed cost of care for each patient with diabetes increased from $822 to $1395 PMPM. In the longitudinal analysis, the difference between the screening cohorts’ mean incremental cost increase was $185 between the 0- and 1–4–year cohorts (P <.003) and $202 between the 0- and 5–7–year cohorts (P <.023). The cost differences between the other cohorts, including $217 between the 0- and 8–10–year cohorts (P <.066), were not statistically significant. Conclusions Based on our analysis, the annual retinopathy screening rate for patients with diabetes has remained low since 2001, and has been well below the guideline-recommended screening levels. For patients with type 2 diabetes, the mean increase in healthcare expenditures over a 10-year period after diagnosis is not statistically different among those with various retinopathy screening rates, although the increase in healthcare spending is lower for patients with diabetes who were not screened for retinopathy compared with patients who did get screened. PMID:26557224

Exome-chip meta-analysis identifies association between variation in ANKRD26 and platelet aggregation.

PubMed

Chen, Ming-Huei; Yanek, Lisa R; Backman, Joshua D; Eicher, John D; Huffman, Jennifer E; Ben-Shlomo, Yoav; Beswick, Andrew D; Yerges-Armstrong, Laura M; Shuldiner, Alan R; O'Connell, Jeffrey R; Mathias, Rasika A; Becker, Diane M; Becker, Lewis C; Lewis, Joshua P; Johnson, Andrew D; Faraday, Nauder

2017-11-29

Previous genome-wide association studies (GWAS) have identified several variants associated with platelet function phenotypes; however, the proportion of variance explained by the identified variants is mostly small. Rare coding variants, particularly those with high potential for impact on protein structure/function, may have substantial impact on phenotype but are difficult to detect by GWAS. The main purpose of this study was to identify low frequency or rare variants associated with platelet function using genotype data from the Illumina HumanExome Bead Chip. Three family-based cohorts of European ancestry, including ~4,000 total subjects, comprised the discovery cohort and two independent cohorts, one of European and one of African American ancestry, were used for replication. Optical aggregometry in platelet-rich plasma was performed in all the discovery cohorts in response to adenosine diphosphate (ADP), epinephrine, and collagen. Meta-analyses were performed using both gene-based and single nucleotide variant association methods. The gene-based meta-analysis identified a significant association (P = 7.13 × 10 -7 ) between rare genetic variants in ANKRD26 and ADP-induced platelet aggregation. One of the ANKRD26 SNVs - rs191015656, encoding a threonine to isoleucine substitution predicted to alter protein structure/function, was replicated in Europeans. Aggregation increases of ~20-50% were observed in heterozygotes in all cohorts. Novel genetic signals in ABCG1 and HCP5 were also associated with platelet aggregation to ADP in meta-analyses, although only results for HCP5 could be replicated. The SNV in HCP5 intersects epigenetic signatures in CD41+ megakaryocytes suggesting a new functional role in platelet biology for HCP5. This is the first study to use gene-based association methods from SNV array genotypes to identify rare variants related to platelet function. The molecular mechanisms and pathophysiological relevance for the identified genetic associations requires further study.

Post-Secondary Attendance by Parental Income in the U.S. and Canada: What Role for Financial Aid Policy? NBER Working Paper No. 17218

ERIC Educational Resources Information Center

Belley, Philippe; Frenette, Marc; Lochner, Lance

2011-01-01

This paper examines the implications of tuition and need-based financial aid policies for family income--post-secondary (PS) attendance relationships. We first conduct a parallel empirical analysis of the effects of parental income on PS attendance for recent high school cohorts in both the U.S. and Canada using data from the 1997 Cohort of the…

The Contribution of Early Language Development to Children's Emotional and Behavioural Functioning at 6 Years: An Analysis of Data from the Children in Focus Sample from the ALSPAC Birth Cohort

ERIC Educational Resources Information Center

Clegg, Judy; Law, James; Rush, Robert; Peters, Tim J.; Roulstone, Susan

2015-01-01

Background: An association between children's early language development and their emotional and behavioural functioning is reported in the literature. The nature of the association remains unclear and it has not been established if such an association is found in a population-based cohort in addition to clinical populations. Methods: This study…

Global teaching and training initiatives for emerging cohort studies

PubMed Central

Paulus, Jessica K.; Santoyo-Vistrain, Rocío; Havelick, David; Cohen, Amy; Kalyesubula, Robert; Ajayi, Ikeoluwapo O.; Mattsson, Jens G.; Adami, Hans-Olov; Dalal, Shona

2015-01-01

A striking disparity exists across the globe, with essentially no large-scale longitudinal studies ongoing in regions that will be significantly affected by the oncoming non-communicable disease epidemic. The successful implementation of cohort studies in most low-resource research environments presents unique challenges that may be aided by coordinated training programs. Leaders of emerging cohort studies attending the First World Cohort Integration Workshop were surveyed about training priorities, unmet needs and potential cross-cohort solutions to these barriers through an electronic pre-workshop questionnaire and focus groups. Cohort studies representing India, Mexico, Nigeria, South Africa, Sweden, Tanzania and Uganda described similar training needs, including on-the-job training, data analysis software instruction, and database and bio-bank management. A lack of funding and protected time for training activities were commonly identified constraints. Proposed solutions include a collaborative cross-cohort teaching platform with web-based content and interactive teaching methods for a range of research personnel. An international network for research mentorship and idea exchange, and modifying the graduate thesis structure were also identified as key initiatives. Cross-cohort integrated educational initiatives will efficiently meet shared needs, catalyze the development of emerging cohorts, speed closure of the global disparity in cohort research, and may fortify scientific capacity development in low-resource settings. PMID:23856451

Methodology Series Module 1: Cohort Studies

PubMed Central

Setia, Maninder Singh

2016-01-01

Cohort design is a type of nonexperimental or observational study design. In a cohort study, the participants do not have the outcome of interest to begin with. They are selected based on the exposure status of the individual. They are then followed over time to evaluate for the occurrence of the outcome of interest. Some examples of cohort studies are (1) Framingham Cohort study, (2) Swiss HIV Cohort study, and (3) The Danish Cohort study of psoriasis and depression. These studies may be prospective, retrospective, or a combination of both of these types. Since at the time of entry into the cohort study, the individuals do not have outcome, the temporality between exposure and outcome is well defined in a cohort design. If the exposure is rare, then a cohort design is an efficient method to study the relation between exposure and outcomes. A retrospective cohort study can be completed fast and is relatively inexpensive compared with a prospective cohort study. Follow-up of the study participants is very important in a cohort study, and losses are an important source of bias in these types of studies. These studies are used to estimate the cumulative incidence and incidence rate. One of the main strengths of a cohort study is the longitudinal nature of the data. Some of the variables in the data will be time-varying and some may be time independent. Thus, advanced modeling techniques (such as fixed and random effects models) are useful in analysis of these studies. PMID:26955090

Methodology Series Module 1: Cohort Studies.

PubMed

Setia, Maninder Singh

2016-01-01

Cohort design is a type of nonexperimental or observational study design. In a cohort study, the participants do not have the outcome of interest to begin with. They are selected based on the exposure status of the individual. They are then followed over time to evaluate for the occurrence of the outcome of interest. Some examples of cohort studies are (1) Framingham Cohort study, (2) Swiss HIV Cohort study, and (3) The Danish Cohort study of psoriasis and depression. These studies may be prospective, retrospective, or a combination of both of these types. Since at the time of entry into the cohort study, the individuals do not have outcome, the temporality between exposure and outcome is well defined in a cohort design. If the exposure is rare, then a cohort design is an efficient method to study the relation between exposure and outcomes. A retrospective cohort study can be completed fast and is relatively inexpensive compared with a prospective cohort study. Follow-up of the study participants is very important in a cohort study, and losses are an important source of bias in these types of studies. These studies are used to estimate the cumulative incidence and incidence rate. One of the main strengths of a cohort study is the longitudinal nature of the data. Some of the variables in the data will be time-varying and some may be time independent. Thus, advanced modeling techniques (such as fixed and random effects models) are useful in analysis of these studies.

Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

PubMed Central

Davies, G; Armstrong, N; Bis, J C; Bressler, J; Chouraki, V; Giddaluru, S; Hofer, E; Ibrahim-Verbaas, C A; Kirin, M; Lahti, J; van der Lee, S J; Le Hellard, S; Liu, T; Marioni, R E; Oldmeadow, C; Postmus, I; Smith, A V; Smith, J A; Thalamuthu, A; Thomson, R; Vitart, V; Wang, J; Yu, L; Zgaga, L; Zhao, W; Boxall, R; Harris, S E; Hill, W D; Liewald, D C; Luciano, M; Adams, H; Ames, D; Amin, N; Amouyel, P; Assareh, A A; Au, R; Becker, J T; Beiser, A; Berr, C; Bertram, L; Boerwinkle, E; Buckley, B M; Campbell, H; Corley, J; De Jager, P L; Dufouil, C; Eriksson, J G; Espeseth, T; Faul, J D; Ford, I; Scotland, Generation; Gottesman, R F; Griswold, M E; Gudnason, V; Harris, T B; Heiss, G; Hofman, A; Holliday, E G; Huffman, J; Kardia, S L R; Kochan, N; Knopman, D S; Kwok, J B; Lambert, J-C; Lee, T; Li, G; Li, S-C; Loitfelder, M; Lopez, O L; Lundervold, A J; Lundqvist, A; Mather, K A; Mirza, S S; Nyberg, L; Oostra, B A; Palotie, A; Papenberg, G; Pattie, A; Petrovic, K; Polasek, O; Psaty, B M; Redmond, P; Reppermund, S; Rotter, J I; Schmidt, H; Schuur, M; Schofield, P W; Scott, R J; Steen, V M; Stott, D J; van Swieten, J C; Taylor, K D; Trollor, J; Trompet, S; Uitterlinden, A G; Weinstein, G; Widen, E; Windham, B G; Jukema, J W; Wright, A F; Wright, M J; Yang, Q; Amieva, H; Attia, J R; Bennett, D A; Brodaty, H; de Craen, A J M; Hayward, C; Ikram, M A; Lindenberger, U; Nilsson, L-G; Porteous, D J; Räikkönen, K; Reinvang, I; Rudan, I; Sachdev, P S; Schmidt, R; Schofield, P R; Srikanth, V; Starr, J M; Turner, S T; Weir, D R; Wilson, J F; van Duijn, C; Launer, L; Fitzpatrick, A L; Seshadri, S; Mosley, T H; Deary, I J

2015-01-01

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10−9, MIR2113; rs17522122, P=2.55 × 10−8, AKAP6; rs10119, P=5.67 × 10−9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10−6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10−17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C. PMID:25644384

Whether the Autism Spectrum Quotient Consists of Two Different Subgroups? Cluster Analysis of the Autism Spectrum Quotient in General Population

ERIC Educational Resources Information Center

Kitazoe, Noriko; Fujita, Naofumi; Izumoto, Yuji; Terada, Shin-ichi; Hatakenaka, Yuhei

2017-01-01

The purpose of this study was to investigate whether the individuals in the general population with high scores on the Autism Spectrum Quotient constituted a single homogeneous group or not. A cohort of university students (n = 4901) was investigated by cluster analysis based on the original five subscales of the Autism Spectrum Quotient. Based on…

Spatial gender-age-period-cohort analysis of pancreatic cancer mortality in Spain (1990–2013)

PubMed Central

Etxeberria, Jaione; Goicoa, Tomás; López-Abente, Gonzalo; Riebler, Andrea

2017-01-01

Recently, the interest in studying pancreatic cancer mortality has increased due to its high lethality. In this work a detailed analysis of pancreatic cancer mortality in Spanish provinces was performed using recent data. A set of multivariate spatial gender-age-period-cohort models was considered to look for potential candidates to analyze pancreatic cancer mortality rates. The selected model combines features of APC (age-period-cohort) models with disease mapping approaches. To ensure model identifiability sum-to-zero constraints were applied. A fully Bayesian approach based on integrated nested Laplace approximations (INLA) was considered for model fitting and inference. Sensitivity analyses were also conducted. In general, estimated average rates by age, cohort, and period are higher in males than in females. The higher differences according to age between males and females correspond to the age groups [65, 70), [70, 75), and [75, 80). Regarding the cohort, the greatest difference between men and women is observed for those born between the forties and the sixties. From there on, the younger the birth cohort is, the smaller the difference becomes. Some cohort differences are also identified by regions and age-groups. The spatial pattern indicates a North-South gradient of pancreatic cancer mortality in Spain, the provinces in the North being the ones with the highest effects on mortality during the studied period. Finally, the space-time evolution shows that the space pattern has changed little over time. PMID:28199327

The prevalence of patellofemoral osteoarthritis: a systematic review and meta-analysis.

PubMed

Kobayashi, S; Pappas, E; Fransen, M; Refshauge, K; Simic, M

2016-10-01

To determine the prevalence of radiographic patellofemoral osteoarthritis (OA) from population- and symptom-based cohorts and to evaluate if knee pain, physical function and quality of life (QOL) differ between people with isolated patellofemoral OA, isolated tibiofemoral OA and combined patellofemoral and tibiofemoral OA. Terms associated with "patellofemoral OA", "prevalence" and "clinical features" were used to search Medline, EMBASE, CINAHL, SCOPUS, AMED and Web of Science databases with no language restriction' from inception to August 2014. Two independent reviewers screened papers for eligibility. Studies were included if they reported prevalence of compartmental patterns of radiographic knee OA in population- or symptom-based cohorts. Studies were excluded if they evaluated a targeted sample (e.g., occupation-specific participants) or repeated already reported data from the same cohorts. Point prevalence estimates of patellofemoral OA were extracted from eligible studies, pooled and quantitatively analysed. A critical appraisal tool was used to evaluate methodological quality. The search yielded 1891 records. The inclusion criteria were met by 32 studies. The crude prevalence of patellofemoral OA was 25% in the population-based cohorts (aged >20 years) and 39% in the symptom-based cohorts (aged >30 years). Eight studies reported knee pain, physical function and QOL in people with different compartmental disease; however no significant differences were found. These findings confirm the substantial prevalence of patellofemoral OA, demonstrating the need to specifically consider the patellofemoral joint in knee OA research and clinical settings. Copyright © 2016. Published by Elsevier Ltd.

Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals†

PubMed Central

Rivera, Margarita; Locke, Adam E.; Corre, Tanguy; Czamara, Darina; Wolf, Christiane; Ching-Lopez, Ana; Milaneschi, Yuri; Kloiber, Stefan; Cohen-Woods, Sara; Rucker, James; Aitchison, Katherine J.; Bergmann, Sven; Boomsma, Dorret I.; Craddock, Nick; Gill, Michael; Holsboer, Florian; Hottenga, Jouke-Jan; Korszun, Ania; Kutalik, Zoltan; Lucae, Susanne; Maier, Wolfgang; Mors, Ole; Müller-Myhsok, Bertram; Owen, Michael J.; Penninx, Brenda W. J. H.; Preisig, Martin; Rice, John; Rietschel, Marcella; Tozzi, Federica; Uher, Rudolf; Vollenweider, Peter; Waeber, Gerard; Willemsen, Gonneke; Craig, Ian W.; Farmer, Anne E.; Lewis, Cathryn M.; Breen, Gerome; McGuffin, Peter

2017-01-01

Background Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity. Aims To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis. Method The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT. Results In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β = 0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO. Conclusions This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression. PMID:28642257

Assessing copy number from exome sequencing and exome array CGH based on CNV spectrum in a large clinical cohort.

PubMed

Retterer, Kyle; Scuffins, Julie; Schmidt, Daniel; Lewis, Rachel; Pineda-Alvarez, Daniel; Stafford, Amanda; Schmidt, Lindsay; Warren, Stephanie; Gibellini, Federica; Kondakova, Anastasia; Blair, Amanda; Bale, Sherri; Matyakhina, Ludmila; Meck, Jeanne; Aradhya, Swaroop; Haverfield, Eden

2015-08-01

Detection of copy-number variation (CNV) is important for investigating many genetic disorders. Testing a large clinical cohort by array comparative genomic hybridization provides a deep perspective on the spectrum of pathogenic CNV. In this context, we describe a bioinformatics approach to extract CNV information from whole-exome sequencing and demonstrate its utility in clinical testing. Exon-focused arrays and whole-genome chromosomal microarray analysis were used to test 14,228 and 14,000 individuals, respectively. Based on these results, we developed an algorithm to detect deletions/duplications in whole-exome sequencing data and a novel whole-exome array. In the exon array cohort, we observed a positive detection rate of 2.4% (25 duplications, 318 deletions), of which 39% involved one or two exons. Chromosomal microarray analysis identified 3,345 CNVs affecting single genes (18%). We demonstrate that our whole-exome sequencing algorithm resolves CNVs of three or more exons. These results demonstrate the clinical utility of single-exon resolution in CNV assays. Our whole-exome sequencing algorithm approaches this resolution but is complemented by a whole-exome array to unambiguously identify intragenic CNVs and single-exon changes. These data illustrate the next advancements in CNV analysis through whole-exome sequencing and whole-exome array.Genet Med 17 8, 623-629.

Empirical performance of the calibrated self-controlled cohort analysis within temporal pattern discovery: lessons for developing a risk identification and analysis system.

PubMed

Norén, G Niklas; Bergvall, Tomas; Ryan, Patrick B; Juhlin, Kristina; Schuemie, Martijn J; Madigan, David

2013-10-01

Observational healthcare data offer the potential to identify adverse drug reactions that may be missed by spontaneous reporting. The self-controlled cohort analysis within the Temporal Pattern Discovery framework compares the observed-to-expected ratio of medical outcomes during post-exposure surveillance periods with those during a set of distinct pre-exposure control periods in the same patients. It utilizes an external control group to account for systematic differences between the different time periods, thus combining within- and between-patient confounder adjustment in a single measure. To evaluate the performance of the calibrated self-controlled cohort analysis within Temporal Pattern Discovery as a tool for risk identification in observational healthcare data. Different implementations of the calibrated self-controlled cohort analysis were applied to 399 drug-outcome pairs (165 positive and 234 negative test cases across 4 health outcomes of interest) in 5 real observational databases (four with administrative claims and one with electronic health records). Performance was evaluated on real data through sensitivity/specificity, the area under receiver operator characteristics curve (AUC), and bias. The calibrated self-controlled cohort analysis achieved good predictive accuracy across the outcomes and databases under study. The optimal design based on this reference set uses a 360 days surveillance period and a single control period 180 days prior to new prescriptions. It achieved an average AUC of 0.75 and AUC >0.70 in all but one scenario. A design with three separate control periods performed better for the electronic health records database and for acute renal failure across all data sets. The estimates for negative test cases were generally unbiased, but a minor negative bias of up to 0.2 on the RR-scale was observed with the configurations using multiple control periods, for acute liver injury and upper gastrointestinal bleeding. The calibrated self-controlled cohort analysis within Temporal Pattern Discovery shows promise as a tool for risk identification; it performs well at discriminating positive from negative test cases. The optimal parameter configuration may vary with the data set and medical outcome of interest.

Pattern and process of clonal growth in a common cattail (Typha latifolia L. ) population

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

Dickerman, J.A.

1982-01-01

A detailed analysis of individually identified Typha latifolia shoots quantified the births, deaths, life histories and productivities of the shoots. Three levels of plant structure were addressed: Inter-shoot relationships, individual shoot behavior and leaf dynamics. Shoots emerged in three major emergence pulses each year, and were grouped by these pulses into three major cohorts. The first cohort emerged in early spring, grew throughout the growing season, and died in late autumn. The second cohort emerged in midsummer; 70 to 80 percent of these shoots died in autumn, while the remainder resumed growth in the following spring. The third cohort emergedmore » in late summer and early autumn; 80 to 90 percent of all third cohort shoots resumed growth the following spring. An intrinsic or self-regulation of density through reallocation of assimilates between shoots and rhizomes adequately explained the density patterns. This regulation is based on the growth pattern and the differing roles of the cohorts: The first and third cohorts are predominately regenerative, while the second cohort is proliferative, and fills in shoot density if, in early spring, density is below a shoot saturation level that apparently effectively holds marsh space.« less

Real-world effectiveness and safety of oral anticoagulation strategies in atrial fibrillation: a cohort study based on a German claims dataset.

PubMed

Mueller, Sabrina; Groth, Antje; Spitzer, Stefan G; Schramm, Anja; Pfaff, Andreas; Maywald, Ulf

2018-01-01

To compare the real-world effectiveness and safety of non-vitamin-K-antagonist oral anticoagulant (NOAC) treatment in atrial fibrillation (AF) patients with a vitamin-K-antagonist (VKA)-based treatment. This was a retrospective analysis of an anonymized claims dataset from 3 German health insurance funds covering the period from January 01, 2010 to June 30, 2014, with a minimum observation time of 12 months. All continuously insured patients with at least 2 outpatient AF diagnoses and/or 1 inpatient respective diagnosis who received at least 1 outpatient prescription of a NOAC or VKA were included. Death, ischemic strokes (IS), non-specified strokes, transient ischemic attacks (TIAs), myocardial infarctions (MIs), arterial embolism (AE), hemorrhagic strokes, severe bleedings, and composite outcomes. Main comparisons were done based on propensity score-matched (PSM) cohorts. Results were reported as incidence rate ratios and hazard ratios (HRs). We assigned 37,439 AF patients to each PSM cohort (NOAC cohort: mean age 78.2 years, mean CHA 2 DS 2 VASc score 2.96, mean follow-up 348.5 days; VKA cohort: mean age 78.2 years, mean CHA 2 DS 2 VASc 2.95, mean follow-up 365.5 days). NOAC exposure was associated with significantly higher incidence rate ratios; 95% CI/HRs; 95% CI for the following outcomes: death (1.22; 1.17-1.28/1.22; 1.17-1.28), IS (1.90; 1.69-2.15/1.92; 1.69-2.19), non-specified strokes (2.04; 1.16-3.70/1.93; 1.13-3.32), TIAs (1.52; 1.29-1.79/1.44; 1.21-1.70), MIs (1.26; 1.10-1.15/1.31; 1.13-1.52), AE (1.75; 1.32-2.32/1.81; 1.36-2.34) and severe bleeding (1.92; 1.71-2.15/1.95; 1.74-2.20). Multivariable Cox regression analyses and additional sensitivity analysis, including analysis of PSM-matched NOAC/VKA treatment-naive patients, only confirmed the above results. The study was documented under clinicaltrials.gov (NCT02657616). A VKA therapy seems to be more effective and safer than a NOAC therapy in a real-world cohort of German AF patients.

Validation and Implementation of BRCA1/2 Variant Screening in Ovarian Tumor Tissue.

PubMed

de Jonge, Marthe M; Ruano, Dina; van Eijk, Ronald; van der Stoep, Nienke; Nielsen, Maartje; Wijnen, Juul T; Ter Haar, Natalja T; Baalbergen, Astrid; Bos, Monique E M M; Kagie, Marjolein J; Vreeswijk, Maaike P G; Gaarenstroom, Katja N; Kroep, Judith R; Smit, Vincent T H B M; Bosse, Tjalling; van Wezel, Tom; van Asperen, Christi J

2018-06-21

BRCA1/2 variant analysis in tumor tissue could streamline the referral of patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer to genetic counselors and select patients who benefit most from targeted treatment. We investigated the sensitivity of BRCA1/2 variant analysis in formalin-fixed, paraffin-embedded tumor tissue using a combination of next-generation sequencing and copy number variant multiplex ligation-dependent probe amplification. After optimization using a training cohort of known BRCA1/2 mutation carriers, validation was performed in a prospective cohort (Clinical implementation Of BRCA1/2 screening in ovarian tumor tissue: COBRA-cohort) in which screening of BRCA1/2 tumor DNA and leukocyte germline DNA was performed in parallel. BRCA1 promoter hypermethylation and pedigree analysis were also performed. In the training cohort 45 of 46 germline BRCA1/2 variants were detected (sensitivity 98%). In the COBRA cohort (n=62), all six germline variants were identified (sensitivity 100%), together with five somatic BRCA1/2 variants and eight cases with BRCA1 promoter hypermethylation. In four BRCA1/2 variant-negative patients, surveillance or prophylactic management options were offered based on positive family histories. We conclude that BRCA1/2 formalin-fixed, paraffin-embedded tumor tissue analysis reliably detects BRCA1/2 variants. When taking family history of BRCA1/2 variant-negative patients into account, tumor BRCA1/2 variant screening allows more efficient selection of epithelial ovarian cancer patients for genetic counselling and simultaneously selects patients who benefit most from targeted treatment. Copyright © 2018. Published by Elsevier Inc.

Higher risk of developing a subsequent migraine in adults with nonapnea sleep disorders: A nationwide population-based cohort study.

PubMed

Harnod, Tomor; Wang, Yu-Chiao; Kao, Chia-Hung

2015-05-01

This nationwide population-based cohort study evaluated the effect of nonapnea sleep disorders (NSDs) on the subsequent development of a migraine. We identified 46,777 patients aged 20 years and older who were diagnosed with an NSD (ICD-9-CM: 307.4 or 780.5) and without coding for apnea-sleep disorders (ICD-9-CM: 780.51, 780.53, or 780.57) between 2000 and 2002 as the sleep disorder (SD) cohort. A comparison cohort of 93,552 people was enrolled. We calculated the adjusted hazard ratio (aHR) for developing a migraine (ICD-9-CM: 346) after adjusting for age, sex, comorbidity, and drug use. A Kaplan-Meier analysis was used to measure the cumulative incidence of a migraine between 2 curves until the end of 2011. The cumulative incidence of a migraine was significantly higher in the SD cohort. The aHR for developing a migraine in the SD cohort was 3.52 (95% CI=3.28-3.79). The risk of developing a migraine with an NSD was higher in men (aHR=4.31) than in women (aHR=3.35). The age-stratified effect of an NSD on developing a migraine was highest among patients aged 55 years and younger. Higher risks of developing a migraine were observed among the participants without any comorbidity and without any drug treatment for their insomnia. The findings of this population-based cohort study indicate a higher risk of developing a subsequent migraine in patients with an NSD, which could be considered an independent, predisposing factor for developing subsequent a migraine in adulthood. Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Population-based study of the incidence, complexity, and severity of neurologic disability among survivors weighing 500 through 1250 grams at birth: a comparison of two birth cohorts.

PubMed

Robertson, C M; Hrynchyshyn, G J; Etches, P C; Pain, K S

1992-11-01

Mortality and incidence, complexity, and severity of early childhood neurodevelopmental disability are reported for two cohorts of preterm infants of 500 through 1250 g birth weight. Comparing 1978-1979 (cohort 1) and 1988-1989 (cohort 2), 1-year survival improved from 82 (36%) of 226 to 197 (67%) of 291. Cohort 1 survivors were heavier and more mature than cohort 2 survivors (1047 g vs 930 g, 29.6 vs 27.3 weeks). Parental demographic variables were similar. The incidence of specific disabilities with greater than 97% follow-up to 1.5 years adjusted age did not change: cerebral palsy, 14 (17%) vs 20 (10%); vision loss, 5 (6%) vs 9 (5%); mental retardation, 9 (11%) vs 13 (7%); hearing loss, 3 (4%) vs 7 (4%); and convulsive disorders, 2 (2%) vs 3 (2%). The overall number of disabled children (17 [21%] vs 30 [15%]), complexity of disability (> or = 2 disabilities per child: 11 [13%] vs 10 [5%]), and severity of disability (projected dependency: 6 [7%] vs 10 [5%]) did not differ between cohorts 1 and 2. The cerebral palsy prevalence, based on neonatal survival, dropped from 157 per 1000 to 93 per 1000. Analysis by birth weight-specific categories in 250-g increments did not alter results, but disability rates were highest for those of lowest weight. In contrast to other reports this population-based North American study from a well-developed perinatal regional program reports no increase in incidence, complexity, or severity of disability in preterm infants weighing 500 through 1250 g at birth.

Risk of Parkinson's disease following zolpidem use: a retrospective, population-based cohort study.

PubMed

Huang, Hui-Chun; Tsai, Chon-Haw; Muo, Chih-Hsin; Lin, Kang-Hsu; Lu, Ming-Kuei; Sung, Fung-Chang; Kao, Chia-Hung

2015-01-01

To evaluate the influence of long-term zolpidem use on the incidence of developing Parkinson's disease. 2,961 subjects who used zolpidem for the first time longer than 3 months between 1998 and 2000 were identified in the National Health Insurance system of Taiwan. Subjects without a history of zolpidem use were randomly selected as a comparison cohort and frequency matched to zolpidem users based on age, sex, and index date. The diagnosis of Parkinson's disease was based on the criteria of the International Classification of Diseases, Ninth Revision, Clinical Modification. Its incidence until the end of 2009 was calculated and its hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression models and Kaplan-Meier analysis. The overall incidence of Parkinson's disease was greater among zolpidem users than in the comparison cohort (HR = 1.88; 95% CI, 1.45-2.45). However, there was no difference in Parkinson's disease incidence between these 2 cohorts after 5 years of observation. The risk of Parkinson's disease increased with increasing zolpidem dose, with an HR of 0.70 for low-dose users (< 400 mg/y) and 2.94 for high-dose users (≥ 1,600 mg/y). The incidence of Parkinson's disease was greater in subjects using zolpidem only (HR = 2.35; 95% CI, 1.66-3.33) compared to those using benzodiazepines only (HR = 1.31; 95% CI, 0.91-1.90). By stratified analysis, zolpidem use with concurrent depression (HR = 4.79) increased the risk of Parkinson's disease compared to that of zolpidem users without concurrent depression. Zolpidem use might unmask preclinical Parkinson's disease, especially in patients with depression. However, large population-based, unbiased, randomized trials are warranted to confirm this finding. © Copyright 2015 Physicians Postgraduate Press, Inc.

Pathogenesis-based treatments in primary Sjogren's syndrome using artificial intelligence and advanced machine learning techniques: a systematic literature review.

PubMed

Foulquier, Nathan; Redou, Pascal; Le Gal, Christophe; Rouvière, Bénédicte; Pers, Jacques-Olivier; Saraux, Alain

2018-05-17

Big data analysis has become a common way to extract information from complex and large datasets among most scientific domains. This approach is now used to study large cohorts of patients in medicine. This work is a review of publications that have used artificial intelligence and advanced machine learning techniques to study physio pathogenesis-based treatments in pSS. A systematic literature review retrieved all articles reporting on the use of advanced statistical analysis applied to the study of systemic autoimmune diseases (SADs) over the last decade. An automatic bibliography screening method has been developed to perform this task. The program called BIBOT was designed to fetch and analyze articles from the pubmed database using a list of keywords and Natural Language Processing approaches. The evolution of trends in statistical approaches, sizes of cohorts and number of publications over this period were also computed in the process. In all, 44077 abstracts were screened and 1017 publications were analyzed. The mean number of selected articles was 101.0 (S.D. 19.16) by year, but increased significantly over the time (from 74 articles in 2008 to 138 in 2017). Among them only 12 focused on pSS but none of them emphasized on the aspect of pathogenesis-based treatments. To conclude, medicine progressively enters the era of big data analysis and artificial intelligence, but these approaches are not yet used to describe pSS-specific pathogenesis-based treatment. Nevertheless, large multicentre studies are investigating this aspect with advanced algorithmic tools on large cohorts of SADs patients.

Evaluation of team-based learning in a doctor of physical therapy curriculum in the United States.

PubMed

Lein, Donald H; Lowman, John D; Eidson, Christopher A; Yuen, Hon K

2017-01-01

The purpose of this retrospective study was to evaluate students' academic outcomes after implementation of the team-based learning (TBL) approach in patient/client management courses in an entry-level doctor of physical therapy (DPT) curriculum. The research design of this study involved comparing written and practical exam scores from DPT student cohorts taught with the traditional instructional methods (lecture-based) to those of students from subsequent cohorts taught using the TBL approach in two patient/client management courses: basic skills and cardiopulmonary. For this comparison, the exams used, the number of contact hours and labs, and the instructors who taught these courses remained the same during the transition between these two instructional methods (traditional vs. TBL). The average of all individual course exam scores was used for data analysis. In both courses, there were no meaningful differences in the mean exam scores among students across years of cohorts receiving the same instructional method, which allowed clustering students from different years of cohorts in each course receiving the same instructional method into one group. For both courses, the mean exam score was significantly higher in the TBL group than in the traditional instruction group: basic skills course (P<0.001) and cardiopulmonary course (P<0.001). Student cohorts taught using the TBL approach academically outperformed those who received the traditional instructional method in both entry-level DPT patient/client management courses.

Analysis of cohort studies with multivariate and partially observed disease classification data.

PubMed

Chatterjee, Nilanjan; Sinha, Samiran; Diver, W Ryan; Feigelson, Heather Spencer

2010-09-01

Complex diseases like cancers can often be classified into subtypes using various pathological and molecular traits of the disease. In this article, we develop methods for analysis of disease incidence in cohort studies incorporating data on multiple disease traits using a two-stage semiparametric Cox proportional hazards regression model that allows one to examine the heterogeneity in the effect of the covariates by the levels of the different disease traits. For inference in the presence of missing disease traits, we propose a generalization of an estimating equation approach for handling missing cause of failure in competing-risk data. We prove asymptotic unbiasedness of the estimating equation method under a general missing-at-random assumption and propose a novel influence-function-based sandwich variance estimator. The methods are illustrated using simulation studies and a real data application involving the Cancer Prevention Study II nutrition cohort.

Changing Attitudes Toward Euthanasia and Suicide for Terminally Ill Persons, 1977 to 2016: An Age-Period-Cohort Analysis.

PubMed

Attell, Brandon K

2017-01-01

Several longitudinal studies show that over time the American public has become more approving of euthanasia and suicide for terminally ill persons. Yet, these previous findings are limited because they derive from biased estimates of disaggregated hierarchical data. Using insights from life course sociological theory and cross-classified logistic regression models, I better account for this liberalization process by disentangling the age, period, and cohort effects that contribute to longitudinal changes in these attitudes. The results of the analysis point toward a continued liberalization of both attitudes over time, although the magnitude of change was greater for suicide compared with euthanasia. More fluctuation in the probability of supporting both measures was exhibited for the age and period effects over the cohort effects. In addition, age-based differences in supporting both measures were found between men and women and various religious affiliations.

Methodology Series Module 3: Cross-sectional Studies.

PubMed

Setia, Maninder Singh

2016-01-01

Cross-sectional study design is a type of observational study design. In a cross-sectional study, the investigator measures the outcome and the exposures in the study participants at the same time. Unlike in case-control studies (participants selected based on the outcome status) or cohort studies (participants selected based on the exposure status), the participants in a cross-sectional study are just selected based on the inclusion and exclusion criteria set for the study. Once the participants have been selected for the study, the investigator follows the study to assess the exposure and the outcomes. Cross-sectional designs are used for population-based surveys and to assess the prevalence of diseases in clinic-based samples. These studies can usually be conducted relatively faster and are inexpensive. They may be conducted either before planning a cohort study or a baseline in a cohort study. These types of designs will give us information about the prevalence of outcomes or exposures; this information will be useful for designing the cohort study. However, since this is a 1-time measurement of exposure and outcome, it is difficult to derive causal relationships from cross-sectional analysis. We can estimate the prevalence of disease in cross-sectional studies. Furthermore, we will also be able to estimate the odds ratios to study the association between exposure and the outcomes in this design.

Methodology Series Module 3: Cross-sectional Studies

PubMed Central

Setia, Maninder Singh

2016-01-01

Cross-sectional study design is a type of observational study design. In a cross-sectional study, the investigator measures the outcome and the exposures in the study participants at the same time. Unlike in case–control studies (participants selected based on the outcome status) or cohort studies (participants selected based on the exposure status), the participants in a cross-sectional study are just selected based on the inclusion and exclusion criteria set for the study. Once the participants have been selected for the study, the investigator follows the study to assess the exposure and the outcomes. Cross-sectional designs are used for population-based surveys and to assess the prevalence of diseases in clinic-based samples. These studies can usually be conducted relatively faster and are inexpensive. They may be conducted either before planning a cohort study or a baseline in a cohort study. These types of designs will give us information about the prevalence of outcomes or exposures; this information will be useful for designing the cohort study. However, since this is a 1-time measurement of exposure and outcome, it is difficult to derive causal relationships from cross-sectional analysis. We can estimate the prevalence of disease in cross-sectional studies. Furthermore, we will also be able to estimate the odds ratios to study the association between exposure and the outcomes in this design. PMID:27293245

A Nasal Brush-based Classifier of Asthma Identified by Machine Learning Analysis of Nasal RNA Sequence Data.

PubMed

Pandey, Gaurav; Pandey, Om P; Rogers, Angela J; Ahsen, Mehmet E; Hoffman, Gabriel E; Raby, Benjamin A; Weiss, Scott T; Schadt, Eric E; Bunyavanich, Supinda

2018-06-11

Asthma is a common, under-diagnosed disease affecting all ages. We sought to identify a nasal brush-based classifier of mild/moderate asthma. 190 subjects with mild/moderate asthma and controls underwent nasal brushing and RNA sequencing of nasal samples. A machine learning-based pipeline identified an asthma classifier consisting of 90 genes interpreted via an L2-regularized logistic regression classification model. This classifier performed with strong predictive value and sensitivity across eight test sets, including (1) a test set of independent asthmatic and control subjects profiled by RNA sequencing (positive and negative predictive values of 1.00 and 0.96, respectively; AUC of 0.994), (2) two independent case-control cohorts of asthma profiled by microarray, and (3) five cohorts with other respiratory conditions (allergic rhinitis, upper respiratory infection, cystic fibrosis, smoking), where the classifier had a low to zero misclassification rate. Following validation in large, prospective cohorts, this classifier could be developed into a nasal biomarker of asthma.

Clinical significance of cerebral microbleeds on MRI: A comprehensive meta-analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and dementia in cohort studies (v1).

PubMed

Charidimou, Andreas; Shams, Sara; Romero, Jose R; Ding, Jie; Veltkamp, Roland; Horstmann, Solveig; Eiriksdottir, Gudny; van Buchem, Mark A; Gudnason, Vilmundur; Himali, Jayandra J; Gurol, M Edip; Viswanathan, Anand; Imaizumi, Toshio; Vernooij, Meike W; Seshadri, Sudha; Greenberg, Steven M; Benavente, Oscar R; Launer, Lenore J; Shoamanesh, Ashkan

2018-01-01

Background Cerebral microbleeds can confer a high risk of intracerebral hemorrhage, ischemic stroke, death and dementia, but estimated risks remain imprecise and often conflicting. We investigated the association between cerebral microbleeds presence and these outcomes in a large meta-analysis of all published cohorts including: ischemic stroke/TIA, memory clinic, "high risk" elderly populations, and healthy individuals in population-based studies. Methods Cohorts (with > 100 participants) that assessed cerebral microbleeds presence on MRI, with subsequent follow-up (≥3 months) were identified. The association between cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral hemorrhage, death, and dementia) was quantified using random effects models of (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations. Results We identified 31 cohorts ( n = 20,368): 19 ischemic stroke/TIA ( n = 7672), 4 memory clinic ( n = 1957), 3 high risk elderly ( n = 1458) and 5 population-based cohorts ( n = 11,722). Cerebral microbleeds were associated with an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58-2.89 and adj-HR: 2.09; 95% CI: 1.71-2.57), but the relative increase in future intracerebral hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68-8.08 and adj-HR: 3.93; 95% CI: 2.71-5.69). Cerebral microbleeds were an independent predictor of all-cause mortality (adj-HR: 1.36; 95% CI: 1.24-1.48). In three population-based studies, cerebral microbleeds were independently associated with incident dementia (adj-HR: 1.35; 95% CI: 1.00-1.82). Results were overall consistent in analyses stratified by different populations, but with different degrees of heterogeneity. Conclusions Our meta-analysis shows that cerebral microbleeds predict an increased risk of stroke, death, and dementia and provides up-to-date effect sizes across different clinical settings. These pooled estimates can inform clinical decisions and trials, further supporting cerebral microbleeds role as biomarkers of underlying subclinical brain pathology in research and clinical settings.

An analysis of suicide trends in Scotland 1950-2014: comparison with England & Wales.

PubMed

Dougall, Nadine; Stark, Cameron; Agnew, Tim; Henderson, Rob; Maxwell, Margaret; Lambert, Paul

2017-12-20

Scotland has disproportionately high rates of suicide compared with England. An analysis of trends may help reveal whether rates appear driven more by birth cohort, period or age. A 'birth cohort effect' for England & Wales has been previously reported by Gunnell et al. (B J Psych 182:164-70, 2003). This study replicates this analysis for Scotland, makes comparisons between the countries, and provides information on 'vulnerable' cohorts. Suicide and corresponding general population data were obtained from the National Records of Scotland, 1950 to 2014. Age and gender specific mortality rates were estimated. Age, period and cohort patterns were explored graphically by trend analysis. A pattern was found whereby successive male birth cohorts born after 1940 experienced higher suicide rates, in increasingly younger age groups, echoing findings reported for England & Wales. Young men (aged 20-39) were found to have a marked and statistically significant increase in suicide between those in the 1960 and 1965 birth cohorts. The 1965 cohort peaked in suicide rate aged 35-39, and the subsequent 1970 cohort peaked even younger, aged 25-29; it is possible that these 1965 and 1970 cohorts are at greater mass vulnerability to suicide than earlier cohorts. This was reflected in data for England & Wales, but to a lesser extent. Suicide rates associated with male birth cohorts subsequent to 1975 were less severe, and not statistically significantly different from earlier cohorts, suggestive of an amelioration of any possible influential 'cohort' effect. Scottish female suicide rates for all age groups converged and stabilised over time. Women have not been as affected as men, with less variation in patterns by different birth cohorts and with a much less convincing corresponding pattern suggestive of a 'cohort' effect. Trend analysis is useful in identifying 'vulnerable' cohorts, providing opportunities to develop suicide prevention strategies addressing these cohorts as they age.

Cancer Incidence in Physicians: A Taiwan National Population-based Cohort Study.

PubMed

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

2015-11-01

Cancer has been the leading cause of death in Taiwan since 1982. Physicians have many health-related risk factors which may contribute to cancer, such as rotating night shift, radiation, poor lifestyle, and higher exposure risk to infection and potential carcinogenic drugs. However, the cancer risk in physicians is not clear. In Taiwan's National Health Insurance Research Database, we identified 14,889 physicians as the study cohort and randomly selected 29,778 nonmedical staff patients as the comparison cohort for this national population-based cohort study. Cox proportional-hazard regression was used to compare the cancer risk between physicians and comparisons. Physician subgroups were also analyzed. Physicians had a lower all-cancer risk than did the comparisons (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.76-0.97). In the sex-based analysis, male physicians had a lower all-cancer risk than did male comparisons (HR 0.82, 95% CI 0.73-0.94); and female physicians did not (HR 1.29, 95% CI 0.88-1.91). In the cancer-type analysis, male physicians had a higher risk of prostate cancer (HR 1.72, 95% CI 1.12-2.65) and female physicians had twice the risk of breast cancer (HR 2.00, 95% CI 1.11-3.62) than did comparisons. Cancer risk was not significantly associated with physician specialties. Physicians in Taiwan had a lower all-cancer risk but higher risks for prostate and breast cancer than did the general population. These new epidemiological findings require additional study to clarify possible mechanisms.

Team-based simulations for new surgeons: Does early and often make a difference?

PubMed

AbdelFattah, Kareem R; Spalding, M Chance; Leshikar, David; Gardner, Aimee K

2018-04-01

Current work hour restrictions and the expansion of requirements for surgery residents has led to decreased time on high-acuity rotations such as trauma and acute care surgery. In an effort to improve resident competency, we examined the efficacy of a new team-based trauma curriculum for postgraduate year 1 (PGY1) residents. After completing required Advanced Trauma Life Support certification, PGY1s participated in a series of trauma simulations in 3-person teams from June to August. Scenarios were created to develop skills related to trauma management, teamwork, and communication. Each simulation was followed by video-based debriefing with a faculty facilitator. Clinical performance on a 1-month trauma rotation during the year was assessed by trauma faculty using a 24-item evaluation assessing management of acutely ill patients, leadership, communication, cooperation, and professionalism on a 1 (poor) to 5 (very effective) scale. Performance metrics of this intern class were compared with 2 years of previous cohorts who had not participated in any trauma-focused simulation curricula. One-way analysis of variance was used to examine differences in performance ratings across groups. The 2015 intern class (n = 30) each participated in 6 scenarios during their first 2 months in residency. Trauma as intended specialty and performance on preinternship Advanced Trauma Life Support course were similar across 2013, 2014, and 2015 cohorts. Average performance on the trauma rotation was 3.55 ± 0.56 for the 2013 cohort (n = 11), 3.50 ± 0.57 for the 2014 cohort (n = 11), and 4.35 ± 0.68 for the 2015 cohort (n = 12). Post hoc analyses indicated no difference between means of the 2013 and 2014 cohort. However, the mean of the 2015 cohort was statistically significantly better than both the 2013 cohort (P < .01) and the 2014 cohort (P < .01). Trauma-focused simulation improved PGY1 faculty ratings of performance in the clinical setting compared with previous cohorts with no such simulation experience. Adoption of these curricula is both feasible and beneficial. Copyright © 2017 Elsevier Inc. All rights reserved.

Atlas-based analysis of cardiac shape and function: correction of regional shape bias due to imaging protocol for population studies.

PubMed

Medrano-Gracia, Pau; Cowan, Brett R; Bluemke, David A; Finn, J Paul; Kadish, Alan H; Lee, Daniel C; Lima, Joao A C; Suinesiaputra, Avan; Young, Alistair A

2013-09-13

Cardiovascular imaging studies generate a wealth of data which is typically used only for individual study endpoints. By pooling data from multiple sources, quantitative comparisons can be made of regional wall motion abnormalities between different cohorts, enabling reuse of valuable data. Atlas-based analysis provides precise quantification of shape and motion differences between disease groups and normal subjects. However, subtle shape differences may arise due to differences in imaging protocol between studies. A mathematical model describing regional wall motion and shape was used to establish a coordinate system registered to the cardiac anatomy. The atlas was applied to data contributed to the Cardiac Atlas Project from two independent studies which used different imaging protocols: steady state free precession (SSFP) and gradient recalled echo (GRE) cardiovascular magnetic resonance (CMR). Shape bias due to imaging protocol was corrected using an atlas-based transformation which was generated from a set of 46 volunteers who were imaged with both protocols. Shape bias between GRE and SSFP was regionally variable, and was effectively removed using the atlas-based transformation. Global mass and volume bias was also corrected by this method. Regional shape differences between cohorts were more statistically significant after removing regional artifacts due to imaging protocol bias. Bias arising from imaging protocol can be both global and regional in nature, and is effectively corrected using an atlas-based transformation, enabling direct comparison of regional wall motion abnormalities between cohorts acquired in separate studies.

Comparison of SMR, PMR, and PCMR in a cohort of union members potentially exposed to diesel exhaust emissions.

PubMed Central

Wong, O; Morgan, R W; Kheifets, L; Larson, S R

1985-01-01

A comparison of cause specific standarised mortality ratios (SMRs) and proportionate mortality ratios (PMRs) or proportionate cancer mortality ratios (PCMRs) was made based on the mortality experience of a cohort of 34 156 members of a heavy equipment operators union. Two types of PMRs or PCMRs were used in the comparison: those based on all deaths and those based on deaths known to the union only. The comparison indicated that, for the entire cohort, both types of PMRs were poor indicators for cancer risk and produced a large number of false positives. On the other hand, PCMRs appeared to be better than PMRs for assessing the direction of site specific cancer risk, but they tended to overstate the magnitude of risk. Analysis by duration of union membership or latency indicated that PMRs or PCMRs based on deaths known to the union tended to overestimate the risk of lung cancer by disproportionately larger amounts in groups with shorter time than in groups with longer time. This differential bias had the net effect of reducing the gradient of any trend or eliminating the trend entirely. In conclusion, PMR or PCMR, based on reasonably sufficient death ascertainment, has a certain usefulness in generating hypotheses, but they are not useful or reliable in measuring the magnitude of risk or in detecting trends in dose response analysis. No conclusion should be drawn from either PMR or PCMR. PMID:2410011

Gender and socioeconomic disparities in BMI trajectories in the Seychelles: a cohort analysis based on serial population-based surveys.

PubMed

Rossi, Isabelle A; Rousson, Valentin; Viswanathan, Bharathi; Bovet, Pascal

2011-12-09

The relationship between body mass index (BMI) and socioeconomic status (SES) tends to change over time and across populations. In this study, we examined, separately in men and women, whether the association between BMI and SES changed over successive birth cohorts in the Seychelles (Indian Ocean, African region). We used data from all participants in three surveys conducted in 1989, 1994 and 2004 in independent random samples of the population aged 25-64 years in the Seychelles (N = 3'403). We used linear regression to model mean BMI according to age, cohort, SES and smoking status, allowing for a quadratic term for age to account for a curvilinear relation between BMI and age and interactions between SES and age and between SES and cohorts to test whether the relation between SES and BMI changed across subsequent cohorts. All analyses were performed separately in men and women. BMI increased with age in all birth cohorts. BMI was lower in men of low SES than high SES but was higher in women of low SES than high SES. In all SES categories, BMI increased over successive cohorts (1.24 kg/m2 in men and 1.51 kg/m2 for a 10-year increase in birth cohorts, p < 0.001). The difference in BMI between men or women of high vs. low SES did not change significantly across successive cohorts (the interaction between SES and year of birth of cohort was statistically not significant). Smoking was associated with lower BMI in men and women (respectively -1.55 kg/m2 and 2.46 kg/m2, p < 0.001). Although large differences exist between men and women, social patterning of BMI did not change significantly over successive cohorts in this population of a middle-income country in the African region.

Economically Disadvantaged Children's Transitions into Elementary School: Linking Family Processes, School Contexts, and Educational Policy

ERIC Educational Resources Information Center

Crosnoe, Robert; Cooper, Carey E.

2010-01-01

Working from a core perspective on the developmental implications of economic disadvantage, this study attempted to identify "family-based" mechanisms of economic effects on early learning and their potential "school-based" remedies. Multilevel analysis of the Early Childhood Longitudinal Study-Kindergarten Cohort revealed that…

Preschoolers' Mathematics Skills and Behavior: Analysis of a National Sample

ERIC Educational Resources Information Center

Dobbs-Oates, Jennifer; Robinson, Chanele

2012-01-01

This study investigated the association between children's mathematical skills and their behavior in the prekindergarten year in a national sample of children attending center-based child care. The sample consisted of approximately 5,400 preschoolers in center-based care from the Early Childhood Longitudinal Study--Birth Cohort. Children's math…

Estimated burden of cardiovascular disease and value-based price range for evolocumab in a high-risk, secondary-prevention population in the US payer context.

PubMed

Toth, Peter P; Danese, Mark; Villa, Guillermo; Qian, Yi; Beaubrun, Anne; Lira, Armando; Jansen, Jeroen P

2017-06-01

To estimate real-world cardiovascular disease (CVD) burden and value-based price range of evolocumab for a US-context, high-risk, secondary-prevention population. Burden of CVD was assessed using the UK-based Clinical Practice Research Datalink (CPRD) in order to capture complete CV burden including CV mortality. Patients on standard of care (SOC; high-intensity statins) in CPRD were selected based on eligibility criteria of FOURIER, a phase 3 CV outcomes trial of evolocumab, and categorized into four cohorts: high-risk prevalent atherosclerotic CVD (ASCVD) cohort (n = 1448), acute coronary syndrome (ACS) (n = 602), ischemic stroke (IS) (n = 151), and heart failure (HF) (n = 291) incident cohorts. The value-based price range for evolocumab was assessed using a previously published economic model. The model incorporated CPRD CV event rates and considered CV event reduction rate ratios per 1 mmol/L reduction in low-density lipoprotein-cholesterol (LDL-C) from a meta-analysis of statin trials by the Cholesterol Treatment Trialists Collaboration (CTTC), i.e. CTTC relationship. Multiple-event rates of composite CV events (ACS, IS, or coronary revascularization) per 100 patient-years were 12.3 for the high-risk prevalent ASCVD cohort, and 25.7, 13.3, and 23.3, respectively, for incident ACS, IS, and HF cohorts. Approximately one-half (42%) of the high-risk ASCVD patients with a new CV event during follow-up had a subsequent CV event. Combining these real-world event rates and the CTTC relationship in the economic model, the value-based price range (credible interval) under a willingness-to-pay threshold of $150,000/quality-adjusted life-year gained for evolocumab was $11,990 ($9,341-$14,833) to $16,856 ($12,903-$20,678) in ASCVD patients with baseline LDL-C levels ≥70 mg/dL and ≥100 mg/dL, respectively. Real-world CVD burden is substantial. Using the observed CVD burden in CPRD and the CTTC relationship, the cost-effectiveness analysis showed that, accounting for uncertainties, the expected value-based price for evolocumab is higher than its current annual cost, as long as the payer discount off list price is greater than 20%.

A genome-wide association study of corneal astigmatism: The CREAM Consortium

PubMed Central

Shah, Rupal L.; Li, Qing; Zhao, Wanting; Tedja, Milly S.; Tideman, J. Willem L.; Khawaja, Anthony P.; Fan, Qiao; Yazar, Seyhan; Williams, Katie M.; Verhoeven, Virginie J.M.; Xie, Jing; Wang, Ya Xing; Hess, Moritz; Nickels, Stefan; Lackner, Karl J.; Pärssinen, Olavi; Wedenoja, Juho; Biino, Ginevra; Concas, Maria Pina; Uitterlinden, André; Rivadeneira, Fernando; Jaddoe, Vincent W.V.; Hysi, Pirro G.; Sim, Xueling; Tan, Nicholas; Tham, Yih-Chung; Sensaki, Sonoko; Hofman, Albert; Vingerling, Johannes R.; Jonas, Jost B.; Mitchell, Paul; Hammond, Christopher J.; Höhn, René; Baird, Paul N.; Wong, Tien-Yin; Cheng, Chinfsg-Yu; Teo, Yik Ying; Mackey, David A.; Williams, Cathy; Saw, Seang-Mei; Klaver, Caroline C.W.; Bailey-Wilson, Joan E.

2018-01-01

Purpose To identify genes and genetic markers associated with corneal astigmatism. Methods A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. Results The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha (PDGFRA) gene: top SNP: rs7673984, odds ratio=1.12 (95% CI:1.08–1.16), p=5.55×10−9. No other genome-wide significant loci were identified in the combined analysis or European/Asian ancestry-specific analyses. Gene-based analysis identified three novel candidate genes for corneal astigmatism in Europeans—claudin-7 (CLDN7), acid phosphatase 2, lysosomal (ACP2), and TNF alpha-induced protein 8 like 3 (TNFAIP8L3). Conclusions In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the PDGFRA gene, gene-based analysis identified three novel candidate genes, CLDN7, ACP2, and TNFAIP8L3, that warrant further investigation to understand their role in the pathogenesis of corneal astigmatism. The much lower number of genetic variants and genes demonstrating an association with corneal astigmatism compared to published spherical equivalent GWAS analyses suggest a greater influence of rare genetic variants, non-additive genetic effects, or environmental factors in the development of astigmatism. PMID:29422769

Cost-Utility Analysis of Anterior Cervical Discectomy and Fusion With Plating (ACDFP) Versus Posterior Cervical Foraminotomy (PCF) for Patients With Single-level Cervical Radiculopathy at 1-Year Follow-up.

PubMed

Alvin, Matthew D; Lubelski, Daniel; Abdullah, Kalil G; Whitmore, Robert G; Benzel, Edward C; Mroz, Thomas E

2016-03-01

A retrospective 1-year cost-utility analysis. To determine the cost-effectiveness of anterior cervical discectomy and fusion with plating (ACDFP) in comparison with posterior cervical foraminotomy (PCF) for patients with single-level cervical radiculopathy. Cervical radiculopathy due to cervical spondylosis is commonly treated by either PCF or ACDFP for patients who are refractory to nonsurgical treatment. Although some have suggested superior outcomes with ACDFP as compared with PCF, the former is also associated with greater costs. The present study analyzes the cost-effectiveness of ACDFP versus PCF for patients with single-level cervical radiculopathy. Forty-five patients who underwent ACDFP and 25 patients who underwent PCF for single-level cervical radiculopathy were analyzed. One-year postoperative health outcomes were assessed based on Visual Analogue Scale, Pain Disability Questionnaire, Patient Health Questionnaire, and EuroQOL-5 Dimensions questionnaires to analyze the comparative effectiveness of each procedure. Direct medical costs were estimated using Medicare national payment amounts and indirect costs were based on patient missed work days and patient income. Postoperative 1-year cost/utility ratios and the incremental cost-effectiveness ratio (ICER) were calculated to assess for cost-effectiveness using a threshold of $100,000/QALY gained. The 1-year cost-utility ratio for the PCF cohort was significantly lower ($79,856/QALY gained) than that for the ACDFP cohort ($131,951/QALY gained) (P<0.01). In calculating the 1-year ICER, as the ACDFP cohort showed lower QALY gained than the PCF cohort, the ICER was negative and is not reported, meaning that ACDFP was dominated by PCF. Statistically significant and clinically relevant improvements (through minimum clinically important differences) were seen in both cohorts. Although both cohorts showed improved health outcomes, ACDFP was not cost-effective relative to the threshold of $100,000/QALY gained at 1-year postoperatively, whereas PCF was. The durability of these results must be analyzed with long-term cost-utility analysis studies.

Nitrosourea efficacy in high-grade glioma: a survival gain analysis summarizing 504 cohorts with 24193 patients.

PubMed

Wolff, Johannes E A; Berrak, Su; Koontz Webb, Susannah E; Zhang, Ming

2008-05-01

Even though past studies have suggested efficacy of nitrosourea drugs in patients with high-grade glioma and temozolomide has recently been shown significantly to be beneficial, no conclusive comparisons between these agents have been published. We performed a survival gain analysis of 364 studies describing 24,193 patients with high-grade glioma treated in 504 cohorts, and compared the effects of drugs. The most frequent diagnoses were glioblastoma multiforme (GBM) (72%) and anaplastic astrocytoma (22%). The mean overall survival (mOS) was 14.1 months. The outcome was influenced by several of the known prognostic factors including the histological grade, if the tumors were newly diagnosed or recurrent, the completeness of resection, patients' age, and gender. This information allowed the calculation of a predicted mOS for each cohort based on their prognostic factors independent of treatment. Survival gain to characterize the influence of treatment was subsequently defined and validated as the difference between the observed and the predicted mOS. In 62 CCNU-treated cohorts and 15 ACNU-treated cohorts the survival gain was 5.3 months and 8.9 months (P < 0.0005), respectively. No detectable survival gain for patients treated with various BCNU-containing regimens was found. Conclusion CCNU- and ACNU-containing regimens were superior to BCNU containing regiments.

Effect of age, period and birth-cohort on the frequency of glucose-6-phosphate dehydrogenase deficiency in Sardinian adults.

PubMed

Pes, Giovanni Mario; Errigo, Alessandra; Bitti, Angela; Dore, Maria Pina

2018-02-01

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited disorder common in Sardinia. In this study, the frequency variation of G6PD-deficiency across age groups and birth cohorts was investigated using Age-Period-Cohort analysis. Data were collected from the clinical records of 11,252 patients (6975 women, age range 17-94 years) who underwent endoscopy between 2000 and 2016 at a teaching hospital (University of Sassari), Italy. G6PD status was assessed by enzymatic assay based on G6PD/6GPD ratio. A Poisson log-linear regression model was used to identify age and time trend in G6PD deficiency. Enzyme deficiency was detected in 11.4% of the entire cohort (men: 7.9%; women: 13.6%). Age-Period-Cohort analysis showed no inflection points across age groups, especially after age 80. The effects of time period and birth cohorts on G6PD deficiency were negligible (frequencies before and after 1950 were 11.0% and 11.8%, respectively). These findings indicate that the frequency of G6PD deficiency does not vary significantly in oldest subjects. The lack of evidence for selection across the malaria eradication time may be explained by other factors, including somatic cell selection or misclassification of heterozygotes women as G6PD normal in the older birth cohorts. Additional molecular studies may help clarify these issues. Key message The frequency of glucose-6-phosphate dehydrogenase deficiency is stable across age groups and does not vary in generations born before or after malaria eradication.

Multiple imputation of missing data in nested case-control and case-cohort studies.

PubMed

Keogh, Ruth H; Seaman, Shaun R; Bartlett, Jonathan W; Wood, Angela M

2018-06-05

The nested case-control and case-cohort designs are two main approaches for carrying out a substudy within a prospective cohort. This article adapts multiple imputation (MI) methods for handling missing covariates in full-cohort studies for nested case-control and case-cohort studies. We consider data missing by design and data missing by chance. MI analyses that make use of full-cohort data and MI analyses based on substudy data only are described, alongside an intermediate approach in which the imputation uses full-cohort data but the analysis uses only the substudy. We describe adaptations to two imputation methods: the approximate method (MI-approx) of White and Royston () and the "substantive model compatible" (MI-SMC) method of Bartlett et al. (). We also apply the "MI matched set" approach of Seaman and Keogh () to nested case-control studies, which does not require any full-cohort information. The methods are investigated using simulation studies and all perform well when their assumptions hold. Substantial gains in efficiency can be made by imputing data missing by design using the full-cohort approach or by imputing data missing by chance in analyses using the substudy only. The intermediate approach brings greater gains in efficiency relative to the substudy approach and is more robust to imputation model misspecification than the full-cohort approach. The methods are illustrated using the ARIC Study cohort. Supplementary Materials provide R and Stata code. © 2018, The International Biometric Society.

Diabetes mellitus increases the risk of rotator cuff tear repair surgery: A population-based cohort study.

PubMed

Huang, Shih-Wei; Wang, Wei-Te; Chou, Lin-Chuan; Liou, Tsan-Hon; Chen, Yi-Wen; Lin, Hui-Wen

Rotator cuff tears are the most common cause of shoulder disability in people older than 50years, and surgical intervention is usually required for restoring functioning. However, in patients undergoing rotator cuff repair surgery, patients with DM had poorer functional outcomes than those without DM, and hence, DM is one of the possible risks factor for rotator cut off tear. The aim of this population-based study was to investigate the relationship between DM and the risk of rotator cuff tear in patients receiving rotator cuff repair surgery. In this retrospective longitudinal population-based 7-year cohort study, we investigated the risk of rotator cuff repair surgery in patients with DM. We performed a case-control matched analysis by using data from the Taiwan Longitudinal Health Insurance Database 2005. Patients were enrolled on the basis of the International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes for DM between January 1, 2004, and December 31, 2007. The prevalence and the adjusted hazard ratios (HRs) of a rotator cuff repair surgery in patients with and without DM were estimated according to the Cox proportional hazard regression analysis using the frailty model. The DM and non-DM cohorts comprised 58,652 patients with DM and 117,304 (1:2) patients without DM after matching for age and sex. The incidence of rotator cuff repair surgery was 41 per 100,000 and 26 per 100,000 person-years in the DM and non-DM cohorts, respectively. The HR of rotator cuff repair surgery during the follow-up period was 1.56 (95% confidence interval [CI] 1.25-1.93, p<0.001) for patients with DM. After adjustment for covariates, the adjusted HR of rotator cuff repair surgery was 1.33 (95% CI, 1.05-1.68, p<0.001) in the DM cohort. DM is an independent risk factor for rotator cuff tear repair surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Is there a causal link between knee loading and knee osteoarthritis progression? A systematic review and meta-analysis of cohort studies and randomised trials

PubMed Central

Henriksen, Marius; Creaby, Mark W; Lund, Hans; Juhl, Carsten; Christensen, Robin

2014-01-01

Objective We performed a systematic review, meta-analysis and assessed the evidence supporting a causal link between knee joint loading during walking and structural knee osteoarthritis (OA) progression. Design Systematic review, meta-analysis and application of Bradford Hill's considerations on causation. Data sources We searched MEDLINE, Scopus, AMED, CINAHL and SportsDiscus for prospective cohort studies and randomised controlled trials (RCTs) from 1950 through October 2013. Study eligibility criteria We selected cohort studies and RCTs in which estimates of knee joint loading during walking were used to predict structural knee OA progression assessed by X-ray or MRI. Data analyses Meta-analysis was performed to estimate the combined OR for structural disease progression with higher baseline loading. The likelihood of a causal link between knee joint loading and OA progression was assessed from cohort studies using the Bradford Hill guidelines to derive a 0–4 causation score based on four criteria and examined for confirmation in RCTs. Results Of the 1078 potentially eligible articles, 5 prospective cohort studies were included. The studies included a total of 452 patients relating joint loading to disease progression over 12–72 months. There were very serious limitations associated with the methodological quality of the included studies. The combined OR for disease progression was 1.90 (95% CI 0.85 to 4.25; I2=77%) for each one-unit increment in baseline knee loading. The combined causation score was 0, indicating no causal association between knee loading and knee OA progression. No RCTs were found to confirm or refute the findings from the cohort studies. Conclusions There is very limited and low-quality evidence to support for a causal link between knee joint loading during walking and structural progression of knee OA. Trial registration number CRD42012003253 PMID:25031196

Is there a causal link between knee loading and knee osteoarthritis progression? A systematic review and meta-analysis of cohort studies and randomised trials.

PubMed

Henriksen, Marius; Creaby, Mark W; Lund, Hans; Juhl, Carsten; Christensen, Robin

2014-07-15

We performed a systematic review, meta-analysis and assessed the evidence supporting a causal link between knee joint loading during walking and structural knee osteoarthritis (OA) progression. Systematic review, meta-analysis and application of Bradford Hill's considerations on causation. We searched MEDLINE, Scopus, AMED, CINAHL and SportsDiscus for prospective cohort studies and randomised controlled trials (RCTs) from 1950 through October 2013. We selected cohort studies and RCTs in which estimates of knee joint loading during walking were used to predict structural knee OA progression assessed by X-ray or MRI. Meta-analysis was performed to estimate the combined OR for structural disease progression with higher baseline loading. The likelihood of a causal link between knee joint loading and OA progression was assessed from cohort studies using the Bradford Hill guidelines to derive a 0-4 causation score based on four criteria and examined for confirmation in RCTs. Of the 1078 potentially eligible articles, 5 prospective cohort studies were included. The studies included a total of 452 patients relating joint loading to disease progression over 12-72 months. There were very serious limitations associated with the methodological quality of the included studies. The combined OR for disease progression was 1.90 (95% CI 0.85 to 4.25; I(2)=77%) for each one-unit increment in baseline knee loading. The combined causation score was 0, indicating no causal association between knee loading and knee OA progression. No RCTs were found to confirm or refute the findings from the cohort studies. There is very limited and low-quality evidence to support for a causal link between knee joint loading during walking and structural progression of knee OA. CRD42012003253. 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.

Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994.

PubMed

Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo; Yokoyama, Yoshie; Siribaddana, Sisira H; Hotopf, Matthew; Sumathipala, Athula; Rijsdijk, Fruhling; Tan, Qihua; Zhang, Dongfeng; Pang, Zengchang; Aaltonen, Sari; Heikkilä, Kauko; Öncel, Sevgi Y; Aliev, Fazil; Rebato, Esther; Tarnoki, Adam D; Tarnoki, David L; Christensen, Kaare; Skytthe, Axel; Kyvik, Kirsten O; Silberg, Judy L; Eaves, Lindon J; Maes, Hermine H; Cutler, Tessa L; Hopper, John L; Ordoñana, Juan R; Sánchez-Romera, Juan F; Colodro-Conde, Lucia; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Sung, Joohon; Song, Yun-Mi; Yang, Sarah; Lee, Kayoung; Franz, Carol E; Kremen, William S; Lyons, Michael J; Busjahn, Andreas; Nelson, Tracy L; Whitfield, Keith E; Kandler, Christian; Jang, Kerry L; Gatz, Margaret; Butler, David A; Stazi, Maria A; Fagnani, Corrado; D'Ippolito, Cristina; Duncan, Glen E; Buchwald, Dedra; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth Jf; Martin, Nicholas G; Medland, Sarah E; Montgomery, Grant W; Jeong, Hoe-Uk; Swan, Gary E; Krasnow, Ruth; Magnusson, Patrik Ke; Pedersen, Nancy L; Dahl-Aslan, Anna K; McAdams, Tom A; Eley, Thalia C; Gregory, Alice M; Tynelius, Per; Baker, Laura A; Tuvblad, Catherine; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Lichtenstein, Paul; Spector, Timothy D; Mangino, Massimo; Lachance, Genevieve; Bartels, Meike; van Beijsterveldt, Toos Cem; Willemsen, Gonneke; Burt, S Alexandra; Klump, Kelly L; Harris, Jennifer R; Brandt, Ingunn; Nilsen, Thomas Sevenius; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Corley, Robin P; Hjelmborg, Jacob V B; Goldberg, Jack H; Iwatani, Yoshinori; Watanabe, Mikio; Honda, Chika; Inui, Fujio; Rasmussen, Finn; Huibregtse, Brooke M; Boomsma, Dorret I; Sørensen, Thorkild I A; Kaprio, Jaakko; Silventoinen, Karri

2016-12-14

Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve.

Impact of nutrition support on clinical outcome and cost-effectiveness analysis in patients at nutritional risk: A prospective cohort study with propensity score matching.

PubMed

Zhang, Hui; Wang, Yang; Jiang, Zhu-Ming; Kondrup, Jens; Fang, Hai; Andrews, Martha; Nolan, Marie T; Mu, Shao-Yu; Zhang, Jun; Yu, Kang; Lu, Qian; Kang, Wei-Ming

2017-05-01

There is a lack of evidence regarding the economic effects of nutrition support in patients at nutritional risk. The aim of this study was to perform a cost-effectiveness analysis by comparing an adequate nutrition support cohort with a no-support cohort. A prospective observational study was performed in the surgical and medical gastroenterology wards. We identified patients at nutritional risk and the provision of nutrition support by the staff, unaware of the risk status, was recorded. Cost data were obtained from each patient's statement of accounts, and effectiveness was measured by the rate of infectious complication. To control for potential confounding variables, the propensity score method with matching was carried out. The incremental cost-effectiveness ratio was calculated based on the matched population. We screened 3791 patients, and 440 were recruited for the analysis. Patients in the nutrition support cohort had a lower incidence of infectious complications than those in the no-support cohort (9.1 versus 18.1%; P = 0.007). This result was similar in the 149 propensity matched pairs (9.4 versus 24.2%; P < 0.001). The median hospital length of stay was significantly reduced among the matched nutrition support patients (13 versus 15 d; P < 0.001). The total costs were similar among the matched pairs (US $6219 versus $6161). The incremental cost-effectiveness analysis suggested that nutrition support cost US $392 per patient prevented from having infectious complications. Nutrition support was associated with fewer infectious complications and shorter length of stay in patients at nutritional risk. The incremental cost-effectiveness ratio indicated that nutrition support had not increased costs significantly. Copyright © 2016 Elsevier Inc. All rights reserved.

Colorectal cancer mortality trends in Serbia during 1991-2010: an age-period-cohort analysis and a joinpoint regression analysis.

PubMed

Ilic, Milena; Ilic, Irena

2016-06-22

For both men and women worldwide, colorectal cancer is among the leading causes of cancer-related death. This study aimed to assess the mortality trends of colorectal cancer in Serbia between 1991 and 2010, prior to the introduction of population-based screening. Joinpoint regression analysis was used to estimate average annual percent change (AAPC) with the corresponding 95% confidence interval (CI). Furthermore, age-period-cohort analysis was performed to examine the effects of birth cohort and calendar period on the observed temporal trends. We observed a significantly increased trend in colorectal cancer mortality in Serbia during the study period (AAPC = 1.6%, 95% CI 1.3%-1.8%). Colorectal cancer showed an increased mortality trend in both men (AAPC = 2.0%, 95% CI 1.7%-2.2%) and women (AAPC = 1.0%, 95% CI 0.6%-1.4%). The temporal trend of colorectal cancer mortality was significantly affected by birth cohort (P < 0.05), whereas the study period did not significantly affect the trend (P = 0.072). Colorectal cancer mortality increased for the first several birth cohorts in Serbia (from 1916 to 1955), followed by downward flexion for people born after the 1960s. According to comparability test, overall mortality trends for colon cancer and rectal and anal cancer were not parallel (the final selected model rejected parallelism, P < 0.05). We found that colorectal cancer mortality in Serbia increased considerably over the past two decades. Mortality increased particularly in men, but the trends were different according to age group and subsite. In Serbia, interventions to reduce colorectal cancer burden, especially the implementation of a national screening program, as well as treatment improvements and measures to encourage the adoption of a healthy lifestyle, are needed.

Bleeding risk under selective serotonin reuptake inhibitor (SSRI) antidepressants: A meta-analysis of observational studies.

PubMed

Laporte, Silvy; Chapelle, Céline; Caillet, Pascal; Beyens, Marie-Noëlle; Bellet, Florelle; Delavenne, Xavier; Mismetti, Patrick; Bertoletti, Laurent

2017-04-01

Selective serotonin reuptake inhibitors (SSRIs) have been reported to be potentially associated with an increased risk of bleeding. A meta-analysis of observational studies was conducted to quantify this risk. Case-control and cohort studies investigating bleeding risk under SSRI therapy were retrieved by searching the Medline, Pascal, Google Scholar and Scopus databases. Case-control studies were included if they reported bleeding incidents with and without the use of SSRIs and cohort studies were included if they reported the rate of bleeds among SSRI users and non-users. The main outcome was severe bleeding, whatever the site. Only data concerning SSRI belonging to the ATC class N06AB were used. For both case-control and cohort studies, we recorded the adjusted effect estimates and their 95% confidence intervals (CI). Pooled adjusted odds ratio (OR) estimates were computed for case-control and cohort studies using an inverse-variance model. Meta-analysis of the adjusted ORs of 42 observational studies showed a significant association between SSRI use and the risk of bleeding [OR 1.41 (95% CI 1.27-1.57), random effect model, p<0.0001]. The association was found for the 31 case-control studies (1,255,073 patients), with an increased risk of 41% of bleeding [OR 1.41 (95% CI 1.25-1.60)], as well as for the 11 cohort studies including 187,956 patients [OR 1.36 (95% CI 1.12-1.64)]. Subgroup analyses showed that the association remained constant whatever the characteristics of studies. This meta-analysis shows an increased risk of bleeding of at least 36% (from 12% to 64%) based on the high-level of observational studies with SSRIs use. Copyright © 2016 Elsevier Ltd. All rights reserved.

Empirical and targeted therapy of candidemia with fluconazole versus echinocandins: a propensity score-derived analysis of a population-based, multicentre prospective cohort.

PubMed

López-Cortés, L E; Almirante, B; Cuenca-Estrella, M; Garnacho-Montero, J; Padilla, B; Puig-Asensio, M; Ruiz-Camps, I; Rodríguez-Baño, J

2016-08-01

We compared the clinical efficacy of fluconazole and echinocandins in the treatment of candidemia in real practice. The CANDIPOP study is a prospective, population-based cohort study on candidemia carried out between May 2010 and April 2011 in 29 Spanish hospitals. Using strict inclusion criteria, we separately compared the impact of empirical and targeted therapy with fluconazole or echinocandins on 30-day mortality. Cox regression, including a propensity score (PS) for receiving echinocandins, stratified analysis on the PS quartiles and PS-based matched analyses, were performed. The empirical and targeted therapy cohorts comprised 316 and 421 cases, respectively; 30-day mortality was 18.7% with fluconazole and 33.9% with echinocandins (p 0.02) in the empirical therapy group and 19.8% with fluconazole and 27.7% with echinocandins (p 0.06) in the targeted therapy group. Multivariate Cox regression analysis including PS showed that empirical therapy with fluconazole was associated with better prognosis (adjusted hazard ratio 0.38; 95% confidence interval 0.17-0.81; p 0.01); no differences were found within each PS quartile or in cases matched according to PS. Targeted therapy with fluconazole did not show a significant association with mortality in the Cox regression analysis (adjusted hazard ratio 0.77; 95% confidence interval 0.41-1.46; p 0.63), in the PS quartiles or in PS-matched cases. The results were similar among patients with severe sepsis and septic shock. Empirical or targeted treatment with fluconazole was not associated with increased 30-day mortality compared to echinocandins among adults with candidemia. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Trends in the incidence of dementia: design and methods in the Alzheimer Cohorts Consortium.

PubMed

Chibnik, Lori B; Wolters, Frank J; Bäckman, Kristoffer; Beiser, Alexa; Berr, Claudine; Bis, Joshua C; Boerwinkle, Eric; Bos, Daniel; Brayne, Carol; Dartigues, Jean-Francois; Darweesh, Sirwan K L; Debette, Stephanie; Davis-Plourde, Kendra L; Dufouil, Carole; Fornage, Myriam; Grasset, Leslie; Gudnason, Vilmundur; Hadjichrysanthou, Christoforos; Helmer, Catherine; Ikram, M Arfan; Ikram, M Kamran; Kern, Silke; Kuller, Lewis H; Launer, Lenore; Lopez, Oscar L; Matthews, Fiona; Meirelles, Osorio; Mosley, Thomas; Ower, Alison; Psaty, Bruce M; Satizabal, Claudia L; Seshadri, Sudha; Skoog, Ingmar; Stephan, Blossom C M; Tzourio, Christophe; Waziry, Reem; Wong, Mei Mei; Zettergren, Anna; Hofman, Albert

2017-10-01

Several studies have reported a decline in incidence of dementia which may have large implications for the projected burden of disease, and provide important guidance to preventive efforts. However, reports are conflicting or inconclusive with regard to the impact of gender and education with underlying causes of a presumed declining trend remaining largely unidentified. The Alzheimer Cohorts Consortium aggregates data from nine international population-based cohorts to determine changes in the incidence of dementia since 1990. We will employ Poisson regression models to calculate incidence rates in each cohort and Cox proportional hazard regression to compare 5-year cumulative hazards across study-specific epochs. Finally, we will meta-analyse changes per decade across cohorts, and repeat all analysis stratified by sex, education and APOE genotype. In all cohorts combined, there are data on almost 69,000 people at risk of dementia with the range of follow-up years between 2 and 27. The average age at baseline is similar across cohorts ranging between 72 and 77. Uniting a wide range of disease-specific and methodological expertise in research teams, the first analyses within the Alzheimer Cohorts Consortium are underway to tackle outstanding challenges in the assessment of time-trends in dementia occurrence.

Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.

PubMed

Vasan, Ramachandran S; Glazer, Nicole L; Felix, Janine F; Lieb, Wolfgang; Wild, Philipp S; Felix, Stephan B; Watzinger, Norbert; Larson, Martin G; Smith, Nicholas L; Dehghan, Abbas; Grosshennig, Anika; Schillert, Arne; Teumer, Alexander; Schmidt, Reinhold; Kathiresan, Sekar; Lumley, Thomas; Aulchenko, Yurii S; König, Inke R; Zeller, Tanja; Homuth, Georg; Struchalin, Maksim; Aragam, Jayashri; Bis, Joshua C; Rivadeneira, Fernando; Erdmann, Jeanette; Schnabel, Renate B; Dörr, Marcus; Zweiker, Robert; Lind, Lars; Rodeheffer, Richard J; Greiser, Karin Halina; Levy, Daniel; Haritunians, Talin; Deckers, Jaap W; Stritzke, Jan; Lackner, Karl J; Völker, Uwe; Ingelsson, Erik; Kullo, Iftikhar; Haerting, Johannes; O'Donnell, Christopher J; Heckbert, Susan R; Stricker, Bruno H; Ziegler, Andreas; Reffelmann, Thorsten; Redfield, Margaret M; Werdan, Karl; Mitchell, Gary F; Rice, Kenneth; Arnett, Donna K; Hofman, Albert; Gottdiener, John S; Uitterlinden, Andre G; Meitinger, Thomas; Blettner, Maria; Friedrich, Nele; Wang, Thomas J; Psaty, Bruce M; van Duijn, Cornelia M; Wichmann, H-Erich; Munzel, Thomas F; Kroemer, Heyo K; Benjamin, Emelia J; Rotter, Jerome I; Witteman, Jacqueline C; Schunkert, Heribert; Schmidt, Helena; Völzke, Henry; Blankenberg, Stefan

2009-07-08

Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.

Optimal Use of Available Claims to Identify a Medicare Population Free of Coronary Heart Disease

PubMed Central

Kent, Shia T.; Safford, Monika M.; Zhao, Hong; Levitan, Emily B.; Curtis, Jeffrey R.; Kilpatrick, Ryan D.; Kilgore, Meredith L.; Muntner, Paul

2015-01-01

We examined claims-based approaches for identifying a study population free of coronary heart disease (CHD) using data from 8,937 US blacks and whites enrolled during 2003–2007 in a prospective cohort study linked to Medicare claims. Our goal was to minimize the percentage of persons at study entry with self-reported CHD (previous myocardial infarction or coronary revascularization). We assembled 6 cohorts without CHD claims by requiring 6 months, 1 year, or 2 years of continuous Medicare fee-for-service insurance coverage prior to study entry and using either a fixed-window or all-available look-back period. We examined adding CHD-related claims to our “base algorithm,” which included claims for myocardial infarction and coronary revascularization. Using a 6-month fixed-window look-back period, 17.8% of participants without claims in the base algorithm reported having CHD. This was reduced to 3.6% using an all-available look-back period and adding other CHD claims to the base algorithm. Among cohorts using all-available look-back periods, increasing the length of continuous coverage from 6 months to 1 or 2 years reduced the sample size available without lowering the percentage of persons with self-reported CHD. This analysis demonstrates approaches for developing a CHD-free cohort using Medicare claims. PMID:26443420

Age-period-cohort analysis of suicide mortality by gender among white and black Americans, 1983-2012.

PubMed

Wang, Zhenkun; Yu, Chuanhua; Wang, Jinyao; Bao, Junzhe; Gao, Xudong; Xiang, Huiyun

2016-07-13

Previous studies suggested that the racial differences in U.S. suicide rates are decreasing, particularly for African Americans, but the cause behind the temporal variations has yet to be determined. This study aims to investigate the long-term trends in suicide mortality in the U.S. between 1983 and 2012 and to examine age-, period-, and cohort-specific effects by gender and race. Suicide mortality data were collected from the Web-based Injury Statistics Query and Reporting System (WISQARS) and analyzed with the Joinpoint regression and age-period-cohort (APC) analysis. We found that although age-standardized rate of suicide in white males, white females, black males, and black females all changed at different degrees, the overall situation almost has not changed since these changes offset each other. By APC analysis, while the age effect on suicide demonstrate an obvious difference between white males and females (with the peak at 75 to 79 for white males and 45 to 54 for white females), young black people are predominantly susceptible to suicide (risk peaks in early 20s for black males and late 20s for black females). Cohort effects all showed a descending trend, except that in white males and females which showed an obvious increase peaked in around cohort 1960. There was a similar period effect trend between different genders in the same race group, but between the races, differences were found in the period before 1990 and after 2000. We confirmed that the distinction in age-specific suicide rate patterns does exist by gender and by race after controlling for period and cohort effects, which suggested that minorities' age patterns of suicide may have been masked up by the white people in the whole population. The differences of period effects and cohort effects between white and black Americans were likely to be mainly explained by the difference in race susceptibility to economic depression.

Is Statin Use Associated With Tendon Rupture? A Population-Based Retrospective Cohort Analysis.

PubMed

Contractor, Tahmeed; Beri, Abhimanyu; Gardiner, Joseph C; Tang, Xiaoqin; Dwamena, Francesca C

2015-01-01

Previous case reports and small studies have suggested that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (HMG-CoA-Is) may increase the risk of tendon rupture. We conducted a population-based retrospective cohort evaluation to better assess this relationship. From approximately 800,000 enrollees of a private insurance database, those who were aged ≤64 years with at least 1 year of continuous enrollment were selected. Exposure was defined as initiation of HMG-CoA-I after the beginning of the study period. Each exposed person was matched with 2 controls of similar age and gender. Baseline characteristics, including known risk factors for tendon rupture, were compared between exposed and control cohorts with fidelity to the study's matched design. After adjusting for differences in follow-up and baseline characteristics, incidence rate ratios for tendon rupture was assessed in HMG-CoA-I users and nonusers. A total of 34,749 exposed patients were matched with 69,498 controls. There was no difference in the occurrence of tendon ruptures in HMG-CoA-I users versus nonusers. The results remained unchanged after adjustment for age and gender. In conclusion, this population-based retrospective cohort evaluation suggests that use of HMG-CoA-Is as a group are not associated with tendon rupture.

The fiscal consequences of ADHD in Germany: a quantitative analysis based on differences in educational attainment and lifetime earnings.

PubMed

Kotsopoulos, Nikolaos; Connolly, Mark P; Sobanski, Esther; Postma, Maarten J

2013-03-01

To estimate the long-term fiscal consequences of attention deficit hyperactivity disorder (ADHD) on the German government and social insurance system based on differences in educational attainment and the resulting differences in lifetime earnings compared with non-ADHD cohorts. Differences in educational attainment between ADHD and non-ADHD cohorts were linked to education-specific earnings data. Direct and indirect tax rates and social insurance contributions were linked to differences in lifetime, education-specific earnings to derive lost tax revenue in Germany associated with ADHD. For ADHD and non-ADHD cohorts we derived the age-specific discounted net taxes paid by deducting lifetime transfers from lifetime gross taxes paid. The lifetime net tax revenue for a non-ADHD individual was approximately EUR 80,000 higher compared to an untreated ADHD individual. The fiscal burden of untreated ADHD, based on a cohort of n=31,844 born in 2010, was estimated at EUR 2.5 billion in net tax revenue losses compared with an equally-sized non-ADHD cohort. ADHD interventions providing a small improvement in educational attainment resulted in fiscal benefits from increases in lifetime tax gains. ADHD results in long-term financial loss due to lower education attainment and lifetime reduced earnings and resulting lifetime taxes and social contributions paid. Investments in ADHD interventions allowing more children to achieve their educational potential may offer fiscal benefits generating a positive rate of return.

Variants in TTC25 affect autistic trait in patients with autism spectrum disorder and general population.

PubMed

Vojinovic, Dina; Brison, Nathalie; Ahmad, Shahzad; Noens, Ilse; Pappa, Irene; Karssen, Lennart C; Tiemeier, Henning; van Duijn, Cornelia M; Peeters, Hilde; Amin, Najaf

2017-08-01

Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder with a complex genetic architecture. To identify genetic variants underlying ASD, we performed single-variant and gene-based genome-wide association studies using a dense genotyping array containing over 2.3 million single-nucleotide variants in a discovery sample of 160 families with at least one child affected with non-syndromic ASD using a binary (ASD yes/no) phenotype and a quantitative autistic trait. Replication of the top findings was performed in Psychiatric Genomics Consortium and Erasmus Rucphen Family (ERF) cohort study. Significant association of quantitative autistic trait was observed with the TTC25 gene at 17q21.2 (effect size=10.2, P-value=3.4 × 10 -7 ) in the gene-based analysis. The gene also showed nominally significant association in the cohort-based ERF study (effect=1.75, P-value=0.05). Meta-analysis of discovery and replication improved the association signal (P-value meta =1.5 × 10 -8 ). No genome-wide significant signal was observed in the single-variant analysis of either the binary ASD phenotype or the quantitative autistic trait. Our study has identified a novel gene TTC25 to be associated with quantitative autistic trait in patients with ASD. The replication of association in a cohort-based study and the effect estimate suggest that variants in TTC25 may also be relevant for broader ASD phenotype in the general population. TTC25 is overexpressed in frontal cortex and testis and is known to be involved in cilium movement and thus an interesting candidate gene for autistic trait.

Caregiving Antecedents of Secure Base Script Knowledge: A Comparative Analysis of Young Adult Attachment Representations

ERIC Educational Resources Information Center

Steele, Ryan D.; Waters, Theodore E. A.; Bost, Kelly K.; Vaughn, Brian E.; Truitt, Warren; Waters, Harriet S.; Booth-LaForce, Cathryn; Roisman, Glenn I.

2014-01-01

Based on a subsample (N = 673) of the NICHD Study of Early Child Care and Youth Development (SECCYD) cohort, this article reports data from a follow-up assessment at age 18 years on the antecedents of "secure base script knowledge", as reflected in the ability to generate narratives in which attachment-related difficulties are…

Spending on Hospital Care and Pediatric Psychology Service Use Among Adolescents and Young Adults With Cancer.

PubMed

McGrady, Meghan E; Peugh, James L; Brown, Gabriella A; Pai, Ahna L H

2017-10-01

To examine the relationship between need-based pediatric psychology service use and spending on hospital care among adolescents and young adults (AYAs) with cancer. Billing data were obtained from 48 AYAs with cancer receiving need-based pediatric psychology services and a comparison cohort of 48 AYAs with cancer not receiving services. A factorial analysis of covariance examined group differences in spending for hospital care. Pending significant findings, a multivariate analysis of covariance was planned to examine the relationship between need-based pediatric psychology service use and spending for inpatient admissions, emergency department (ED) visits, and outpatient visits. Spending for hospital care was higher among AYAs receiving need-based pediatric psychology services than in the comparison cohort (p < .001, ωPartial2 = .11). Group differences were driven by significantly higher spending for inpatient admissions and ED visits among AYAs receiving need-based pediatric psychology services. The behavioral and psychosocial difficulties warranting need-based pediatric psychology services may predict higher health care spending. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Community-Based Interventions to Improve and Sustain Antiretroviral Therapy Adherence, Retention in HIV Care and Clinical Outcomes in Low- and Middle-Income Countries for Achieving the UNAIDS 90-90-90 Targets

PubMed Central

Adetokunboh, Olatunji; Uthman, Olalekan A.; Knowlton, Amy W.; Altice, Frederick L.; Schechter, Mauro; Galárraga, Omar; Geng, Elvin; Peltzer, Karl; Chang, Larry W.; Van Cutsem, Gilles; Jaffar, Shabbar S.; Ford, Nathan; Mellins, Claude A.; Remien, Robert H.; Mills, Edward J.

2017-01-01

Little is known about the effect of community versus health facility-based interventions to improve and sustain antiretroviral therapy (ART) adherence, virologic suppression, and retention in care among HIV-infected individuals in low-and middle-income countries (LMICs). We systematically searched four electronic databases for all available randomized controlled trials (RCTs) and comparative cohort studies in LMICs comparing community versus health facility-based interventions. Relative risks (RRs) for pre-defined adherence, treatment engagement (linkage and retention in care), and relevant clinical outcomes were pooled using random effect models. Eleven cohort studies and eleven RCTs (N = 97,657) were included. Meta-analysis of the included RCTs comparing community- versus health facility-based interventions found comparable outcomes in terms of ART adherence (RR = 1.02, 95 % CI 0.99 to 1.04), virologic suppression (RR = 1.00, 95 % CI 0.98 to 1.03), and all-cause mortality (RR = 0.93, 95 % CI 0.73 to 1.18). The result of pooled analysis from the RCTs (RR = 1.03, 95 % CI 1.01 to 1.06) and cohort studies (RR = 1.09, 95 % CI 1.03 to 1.15) found that participants assigned to community-based interventions had statistically significantly higher rates of treatment engagement. Two studies found community-based ART delivery model either cost-saving or cost-effective. Community- versus facility-based models of ART delivery resulted in at least comparable outcomes for clinically stable HIV-infected patients on treatment in LMICs and are likely to be cost-effective. PMID:27475643

Identification and validation of distinct biological phenotypes in patients with acute respiratory distress syndrome by cluster analysis.

PubMed

Bos, L D; Schouten, L R; van Vught, L A; Wiewel, M A; Ong, D S Y; Cremer, O; Artigas, A; Martin-Loeches, I; Hoogendijk, A J; van der Poll, T; Horn, J; Juffermans, N; Calfee, C S; Schultz, M J

2017-10-01

We hypothesised that patients with acute respiratory distress syndrome (ARDS) can be clustered based on concentrations of plasma biomarkers and that the thereby identified biological phenotypes are associated with mortality. Consecutive patients with ARDS were included in this prospective observational cohort study. Cluster analysis of 20 biomarkers of inflammation, coagulation and endothelial activation provided the phenotypes in a training cohort, not taking any outcome data into account. Logistic regression with backward selection was used to select the most predictive biomarkers, and these predicted phenotypes were validated in a separate cohort. Multivariable logistic regression was used to quantify the independent association with mortality. Two phenotypes were identified in 454 patients, which we named 'uninflamed' (N=218) and 'reactive' (N=236). A selection of four biomarkers (interleukin-6, interferon gamma, angiopoietin 1/2 and plasminogen activator inhibitor-1) could be used to accurately predict the phenotype in the training cohort (area under the receiver operating characteristics curve: 0.98, 95% CI 0.97 to 0.99). Mortality rates were 15.6% and 36.4% (p<0.001) in the training cohort and 13.6% and 37.5% (p<0.001) in the validation cohort (N=207). The 'reactive phenotype' was independent from confounders associated with intensive care unit mortality (training cohort: OR 1.13, 95% CI 1.04 to 1.23; validation cohort: OR 1.18, 95% CI 1.06 to 1.31). Patients with ARDS can be clustered into two biological phenotypes, with different mortality rates. Four biomarkers can be used to predict the phenotype with high accuracy. The phenotypes were very similar to those found in cohorts derived from randomised controlled trials, and these results may improve patient selection for future clinical trials targeting host response in patients with ARDS. 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/.

Economic crisis and smoking behaviour: prospective cohort study in Iceland

PubMed Central

McClure, Christopher Bruce; Valdimarsdóttir, Unnur A; Hauksdóttir, Arna; Kawachi, Ichiro

2012-01-01

Objective To examine the associations between the 2008 economic collapse in Iceland and smoking behaviour at the national and individual levels. Design A population-based, prospective cohort study based on a mail survey (Health and Wellbeing in Iceland) assessed in 2007 and 2009. Setting National mail survey. Participants Representative cohort (n=3755) of Icelandic adults. Main outcome measure Smoking status. Results A significant reduction in the prevalence of smoking was observed from 2007 (pre-economic collapse) to 2009 (postcollapse) in both males (17.4–14.8%; p 0.01) and females (20.0–17.5%; p 0.01) in the cohort (n=3755). At the individual level of analysis, male former smokers experiencing a reduction in income during the same period were less likely to relapse (OR 0.37; 95% CI 0.16 to 0.85). Female smokers were less likely to quit over time compared to males (OR 0.65; 95% CI 0.45 to 0.93). Among male former smokers who experienced an increase in income between 2007 and 2009, we observed an elevated risk of smoking relapse (OR 4.02; 95% CI 1.15 to 14.00). Conclusions The national prevalence of smoking in Iceland declined following the 2008 economic crisis. This could be due to the procyclical relationship between macro-economic conditions and smoking behaviour (ie, hard times lead to less smoking because of lower affordability), or it may simply reflect a continuation of trends already in place prior to the crisis. In individual-level analysis, we find that former smokers who experienced a decline in income were less likely to relapse; and conversely, an increase in income raises the risk. However, caution is warranted since these findings are based on small numbers. PMID:23048059

Development and validation of a risk-prediction nomogram for in-hospital mortality in adults poisoned with drugs and nonpharmaceutical agents

PubMed Central

Lionte, Catalina; Sorodoc, Victorita; Jaba, Elisabeta; Botezat, Alina

2017-01-01

Abstract Acute poisoning with drugs and nonpharmaceutical agents represents an important challenge in the emergency department (ED). The objective is to create and validate a risk-prediction nomogram for use in the ED to predict the risk of in-hospital mortality in adults from acute poisoning with drugs and nonpharmaceutical agents. This was a prospective cohort study involving adults with acute poisoning from drugs and nonpharmaceutical agents admitted to a tertiary referral center for toxicology between January and December 2015 (derivation cohort) and between January and June 2016 (validation cohort). We used a program to generate nomograms based on binary logistic regression predictive models. We included variables that had significant associations with death. Using regression coefficients, we calculated scores for each variable, and estimated the event probability. Model validation was performed using bootstrap to quantify our modeling strategy and using receiver operator characteristic (ROC) analysis. The nomogram was tested on a separate validation cohort using ROC analysis and goodness-of-fit tests. Data from 315 patients aged 18 to 91 years were analyzed (n = 180 in the derivation cohort; n = 135 in the validation cohort). In the final model, the following variables were significantly associated with mortality: age, laboratory test results (lactate, potassium, MB isoenzyme of creatine kinase), electrocardiogram parameters (QTc interval), and echocardiography findings (E wave velocity deceleration time). Sex was also included to use the same model for men and women. The resulting nomogram showed excellent survival/mortality discrimination (area under the curve [AUC] 0.976, 95% confidence interval [CI] 0.954–0.998, P < 0.0001 for the derivation cohort; AUC 0.957, 95% CI 0.892–1, P < 0.0001 for the validation cohort). This nomogram provides more precise, rapid, and simple risk-analysis information for individual patients acutely exposed to drugs and nonpharmaceutical agents, and accurately estimates the probability of in-hospital death, exclusively using the results of objective tests available in the ED. PMID:28328838

The Social-Emotional Well-Being of Children of Mothers with Intellectual Impairment: A Population-Based Analysis

ERIC Educational Resources Information Center

Hindmarsh, Gabrielle; Llewellyn, Gwynnyth; Emerson, Eric

2017-01-01

Background: Children of parents with intellectual impairment are thought to be at risk for poor social-emotional well-being. This study investigated the relationship between maternal intellectual impairment and poor child social-emotional well-being. Method: Secondary analysis of data from waves 2-4 of the Millennium Cohort Study (UK).…

The role of under-employment and unemployment in recent birth cohort effects in Australian suicide.

PubMed

Page, Andrew; Milner, Allison; Morrell, Stephen; Taylor, Richard

2013-09-01

High suicide rates evident in Australian young adults during an epidemic period in the 1990s appear to have been sustained in older age-groups in the subsequent decade. This period also coincides with changes in employment patterns in Australia. This study investigates age, period, and birth cohort effects in Australian suicide over the 20th century, with particular reference to the period subsequent to the 1990s youth suicide epidemic in young males. Period- and cohort-specific trends in suicide were examined for 1907-2010 based on descriptive analysis of age-specific suicide rates and a series of age-period-cohort (APC) models using Poisson regression. Under-employment rates (those employed part-time seeking additional hours of work) and unemployment rates (those currently seeking employment) for the latter part of this time series (1978-2010) were also examined and compared with period- and cohort-specific trends in suicide. A significant increasing birth cohort effect in male suicide rates was evident in birth cohorts born after 1970-74, after adjusting for the effects age and period. An increasing birth cohort effect was also evident in female suicide rates, but was of a lesser magnitude. Increases in male cohort-specific suicide rates were significantly correlated with increases in cohort-specific under-employment and unemployment rates. Birth cohorts that experienced the peak of the suicide epidemic during the 1990s have continued to have higher suicide rates than cohorts born in earlier epochs. This increase coincides with changes to a labour force characterised by greater 'flexibility' and 'casualised' employment, especially in younger aged cohorts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Periodontal Disease and Incident Lung Cancer Risk: A Meta-Analysis of Cohort Studies.

PubMed

Zeng, Xian-Tao; Xia, Ling-Yun; Zhang, Yong-Gang; Li, Sheng; Leng, Wei-Dong; Kwong, Joey S W

2016-10-01

Periodontal disease is linked to a number of systemic diseases such as cardiovascular diseases and diabetes mellitus. Recent evidence has suggested periodontal disease might be associated with lung cancer. However, their precise relationship is yet to be explored. Hence, this study aims to investigate the association of periodontal disease and risk of incident lung cancer using a meta-analytic approach. PubMed, Scopus, and ScienceDirect were searched up to June 10, 2015. Cohort and nested case-control studies investigating risk of lung cancer in patients with periodontal disease were included. Hazard ratios (HRs) were calculated, as were their 95% confidence intervals (CIs) using a fixed-effect inverse-variance model. Statistical heterogeneity was explored using the Q test as well as the I(2) statistic. Publication bias was assessed by visual inspection of funnel plots symmetry and Egger's test. Five cohort studies were included, involving 321,420 participants in this meta-analysis. Summary estimates based on adjusted data showed that periodontal disease was associated with a significant risk of lung cancer (HR = 1.24, 95% CI = 1.13 to 1.36; I(2) = 30%). No publication bias was detected. Subgroup analysis indicated that the association of periodontal disease and lung cancer remained significant in the female population. Evidence from cohort studies suggests that patients with periodontal disease are at increased risk of developing lung cancer.

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

PubMed

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

2015-11-27

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

South Asians and coronary disease: is there discordance between effects on incidence and prognosis?

PubMed Central

Zaman, M Justin S; Philipson, Pete; Chen, Ruoling; Farag, Ahmed; Shipley, Martin; Marmot, Michael G; Timmis, Adam D; Hemingway, Harry

2013-01-01

Objective To determine whether the effect of South Asian ethnicity differs between studies of incidence and prognosis of coronary disease. Design Systematic literature review and meta-analysis, and cohort analysis from a national acute coronary syndrome (ACS) registry linked to mortality (National Institute of Cardiovascular Outcomes Research/Myocardial Infarction National Audit Project). Setting International for the review, and England and Wales for the cohort analysis. Patients The numbers of South Asians included in the meta-analysis were 111 555 (incidence) and 14 531 (prognosis) of whom 8251 were from the ACS cohort. Main outcome measures Incidence studies: non-fatal myocardial infarction or fatal coronary heart disease; prognostic studies: mortality; HRs for 1-year all-cause death in ACS cohort. Results South Asians had higher incidence of coronary disease compared with white subjects (HR 1.35 95% CI 1.30 to 1.40) based on meta-analysis of nine studies. Among 10 studies on prognosis, South Asians had better prognosis compared with white subjects (HR 0.78 95% CI 0.74 to 0.82). In the ACS cohort, the impact of diabetes (42.4% of South Asians, 16.9% of white subjects) on 1-year mortality was stronger in South Asians than white subjects (age-adjusted HR 1.83 95% CI 1.59 to 2.11 vs 1.53 95% CI 1.49 to 1.57). However, prognosis was better in South Asians even among diabetics, older people and those living in areas of the highest social deprivation. Conclusions South Asian ethnicity is associated with higher incidence of coronary disease, but lower mortality once coronary disease is manifest. The dissociation between effects on incidence and prognosis suggests that public health initiatives to reduce inequalities in mortality between South Asian and white populations should focus on primary prevention. This is a CALIBER study with ClinicalTrials.gov Identifier: NCT01163513. PMID:23406688

Mortality and long-term exposure to ambient air pollution: ongoing analyses based on the American Cancer Society cohort.

PubMed

Krewski, Daniel; Burnett, Richard; Jerrett, Michael; Pope, C Arden; Rainham, Daniel; Calle, Eugenia; Thurston, George; Thun, Michael

This article provides an overview of previous analysis and reanalysis of the American Cancer Society (ACS) cohort, along with an indication of current ongoing analyses of the cohort with additional follow-up information through to 2000. Results of the first analysis conducted by Pope et al. (1995) showed that higher average sulfate levels were associated with increased mortality, particularly from cardiopulmonary disease. A reanalysis of the ACS cohort, undertaken by Krewski et al. (2000), found the original risk estimates for fine-particle and sulfate air pollution to be highly robust against alternative statistical techniques and spatial modeling approaches. A detailed investigation of covariate effects found a significant modifying effect of education with risk of mortality associated with fine particles declining with increasing educational attainment. Pope et al. (2002) subsequently reported results of a subsequent study using an additional 10 yr of follow-up of the ACS cohort. This updated analysis included gaseous copollutant and new fine-particle measurements, more comprehensive information on occupational exposures, dietary variables, and the most recent developments in statistical modeling integrating random effects and nonparametric spatial smoothing into the Cox proportional hazards model. Robust associations between ambient fine particulate air pollution and elevated risks of cardiopulmonary and lung cancer mortality were clearly evident, providing the strongest evidence to date that long-term exposure to fine particles is an important health risk. Current ongoing analysis using the extended follow-up information will explore the role of ecologic, economic, and, demographic covariates in the particulate air pollution and mortality association. This analysis will also provide insight into the role of spatial autocorrelation at multiple geographic scales, and whether critical instances in time of exposure to fine particles influence the risk of mortality from cardiopulmonary and lung cancer. Information on the influence of covariates at multiple scales and of critical exposure time windows can assist policymakers in establishing timelines for regulatory interventions that maximize population health benefits.

Time from HIV seroconversion to death: a collaborative analysis of eight studies in six low and middle-income countries before highly active antiretroviral therapy

PubMed Central

Todd, Jim; Glynn, Judith R.; Marston, Milly; Lutalo, Tom; Biraro, Sam; Mwita, Wambura; Suriyanon, Vinai; Rangsin, Ram; Nelson, Kenrad E.; Sonnenberg, Pam; Fitzgerald, Dan; Karita, Etienne; Żaba, Basia

2018-01-01

Objectives To estimate survival patterns after HIV infection in adults in low and middle-income countries. Design An analysis of pooled data from eight different studies in six countries. Methods HIV seroconverters were included from eight studies (three population-based, two occupational, and three clinic cohorts) if they were at least 15 years of age, and had no more than 4 years between the last HIV-negative and subsequent HIV-positive test. Four strata were defined: East African cohorts; South African miners cohort; Thai cohorts; Haitian clinic cohort. Kaplan–Meier functions were used to estimate survival patterns, and Weibull distributions were used to model and extend survival estimates. Analyses examined the effect of site, age, and sex on survival. Results From 3823 eligible seroconverters, 1079 deaths were observed in 19 671 person-years of follow-up. Survival times varied by age and by study site. Adjusting to age 25–29 years at seroconversion, the median survival was longer in South African miners: 11.6 years [95% confidence interval (CI) 9.8–13.7] and East African cohorts: 11.1 years (95% CI 8.7–14.2) than in Haiti: 8.3 years (95% CI 3.2–21.4) and Thailand: 7.5 years (95% CI 5.4–10.4). Survival was similar for men and women, after adjustment for age at seroconversion and site. Conclusion Without antiretroviral therapy, overall survival after HIV infection in African cohorts was similar to survival in high-income countries, with a similar pattern of faster progression at older ages at seroconversion. Survival appears to be significantly worse in Thailand where other, unmeasured factors may affect progression. PMID:18032940

Increasing incidence of testicular cancer--birth cohort effects.

PubMed

Ekbom, A; Akre, O

1998-01-01

The incidence of testicular cancer is rising in most Western populations. A collaborative study between nine population-based cancer registries in countries around the Baltic Sea was utilized in order to analyze in detail geographic variations and temporal trends in the occurrence of testicular cancer. There were 34,309 cases registered up until 1989 starting in Denmark in 1942 and most recently in Latvia in 1977. From the descriptive epidemiology it was obvious that there was a substantial variation in the age-standardized incidence amounting to about a 10-fold difference between the different countries ranging from 0.8 per 100,000 person-years in Lithuania to 7.6 per 100,000 person-years in Denmark. Previous studies have indicated that this increase is due to birth cohort effects. A more detailed analysis was therefore performed in those six countries with a sufficiently long period of cancer registration; Poland, former East Germany, Norway, Finland, Denmark and Sweden. This analysis showed that birth cohort is a more important determinant of testicular cancer risk than year of diagnosis. In Poland, former East Germany and Finland, there was an increasing risk for all birth cohorts. Among men born in Denmark, Norway or Sweden between 1930 and 1945, this increasing trend in risk was interrupted in these birth cohorts but followed thereafter by an uninterrupted increase by birth cohort. In conclusion, life time exposure to environmental factors which are associated with the incidence of testicular cancer appear to be more related to birth cohort than to year of diagnosis. Because testicular cancer typically occurs at an early age, major etiological factors therefore need to operate early in life, perhaps even in utero.

Kidney and liver organ transplantation in persons with human immunodeficiency virus: An Evidence-Based Analysis.

PubMed

2010-01-01

The objective of this analysis is to determine the effectiveness of solid organ transplantation in persons with end stage organ failure (ESOF) and human immunodeficiency virus (HIV+) CONDITION AND TARGET POPULATION Patients with end stage organ failure who have been unresponsive to other forms of treatment eventually require solid organ transplantation. Similar to persons who are HIV negative (HIV-), persons living with HIV infection (HIV+) are at risk for ESOF from viral (e.g. hepatitis B and C) and non-viral aetiologies (e.g. coronary artery disease, diabetes, hepatocellular carcinoma). Additionally, HIV+ persons also incur risks of ESOF from HIV-associated nephropathy (HIVAN), accelerated liver damage from hepatitis C virus (HCV+), with which an estimated 30% of HIV positive (HIV+) persons are co-infected, and coronary artery disease secondary to antiretroviral therapy. Concerns that the need for post transplant immunosuppression and/or the interaction of immunosuppressive drugs with antiretroviral agents may accelerate the progression of HIV disease, as well as the risk of opportunistic infections post transplantation, have led to uncertainty regarding the overall benefit of transplantation among HIV+ patients. Moreover, the scarcity of donor organs and their use in a population where the clinical benefit of transplantation is uncertain has limited the availability of organ transplantation to persons living with ESOF and HIV. With the development of highly active anti retroviral therapy (HAART), which has been available in Canada since 1997, there has been improved survival and health-related quality of life for persons living with HIV. HAART can suppress HIV replication, enhance immune function, and slow disease progression. HAART managed persons can now be expected to live longer than those in the pre-HAART era and as a result many will now experience ESOF well before they experience life-threatening conditions related to HIV infection. Given their improved prognosis and the burden of illness they may experience from ESOF, the benefit of solid organ transplantation for HIV+ patients needs to be reassessed. What are the effectiveness and cost effectiveness of solid organ transplantation in HIV+ persons with ESOF? A literature search was performed on September 22, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 1996 to September 22, 2009. Systematic review with or without a Meta analysis, RCT, Non-RCT with controlsHIV+ population undergoing solid organ transplantationHIV+ population managed with HAART therapyControls include persons undergoing solid organ transplantation who are i) HIV- ii) HCV+ mono-infected, and iii) HIV+ persons with ESOF not transplanted.Studies that completed and reported results of a Kaplan-Meier Survival Curve analysis.Studies with a minimum (mean or medium) follow up of 1-year.English language citations Case reports and case series were excluded form this review. i) Risk of Death after transplantationii) Death censored graft survival (DCGS)iii) HIV disease progression defined as the post transplant incidence of:- opportunistic infections or neoplasms,- CD4+ T-cell count < 200mm(3), and- any detectable level of plasma HIV viral load.iv) Acute graft rejection,v) Return to dialysis,vi) Recurrence of HCV infection No direct evidence comparing an HIV+ cohort undergoing transplantation with the same not undergoing transplantation (wait list) was found in the literature search. The results of this review are reported for the following comparison cohorts undergoing transplantation: I) KIDNEY TRANSPLANTATION: HIV+ cohort compared with HIV- cohortII) LIVER TRANSPLANTATION: HIV+ cohort compared with HIV- negative cohortIII) LIVER TRANSPLANTATION: HIV+ HCV+ (co-infected) cohort compared with HCV+ (mono-infected) cohort KIDNEY TRANSPLANTATION: HIV+ VS. HIV#ENTITYSTARTX02212; Based on a pooled HIV+ cohort sample size of 285 patients across four studies, the risk of death after kidney transplantation in an HIV+ cohort does not differ to that of an HIV- cohort [hazard ratio (HR): 0.90; 95% CI: 0.36, 2.23]. The quality of evidence supporting this outcome is very low. Death censored graft survival was reported in one study with an HIV+ cohort sample size of 100, and was statistically significantly different (p=.03) to that in the HIV- cohort (n=36,492). However, the quality of evidence supporting this outcome was determined to be very low. There was also uncertainty in the rate of return to dialysis after kidney transplantation in both the HIV+ and HIV- groups and the effect, if any, this may have on patient survival. Because of the very low quality evidence rating, the effect of kidney transplantation on HIV-disease progression is uncertain. The rate of acute graft rejection was determined using the data from one study. There was a nonsignificant difference between the HIV+ and HIV- cohorts (OR 0.13; 95% CI: 0.01, 2.64), although again, because of very low quality evidence there is uncertainty in this estimate of effect. LIVER TRANSPLANTATION: HIV+ VS. HIV#ENTITYSTARTX02212; Based on a combined HIV+ cohort sample size of 198 patient across five studies, the risk of death after liver transplantation in an HIV+ cohort (with at least 50% of the cohort co-infected with HCV+) is statistically significantly 64% greater compared with an HIV- cohort (HR: 1.64; 95% CI: 1.32, 2.02). The quality of evidence supporting this outcome is very low. Death censored graft survival was reported for an HIV+ cohort in one study (n=11) however the DCGS rate of the contemporaneous control HIV- cohort was not reported. Because of sparse data the quality of evidence supporting this outcome is very low indicating death censored graft survival is uncertain. Both the CD4+ T-cell count and HIV viral load appear controlled post transplant with an incidence of opportunistic infection of 20.5%. However, the quality of this evidence for these outcomes is very low indicating uncertainty in these effects. Similarly, because of very low quality evidence there is uncertainty in the rate of acute graft rejection among both the HIV+ and HIV- groups LIVER TRANSPLANTATION: HIV+/HCV+ VS. HCV+ Based on a combined HIV+/HCV+ cohort sample size of 156 from seven studies, the risk of death after liver transplantation is significantly greater (2.8 fold) in a co-infected cohort compared with an HCV+ mono-infected cohort (HR: 2.81; 95% CI: 1.47, 5.37). The quality of evidence supporting this outcome is very low. Death censored graft survival evidence was not available. Regarding disease progression, based on a combined sample size of 71 persons in the co-infected cohort, the CD4+ T-cell count and HIV viral load appear controlled post transplant; however, again the quality of evidence supporting this outcome is very low. The rate of opportunistic infection in the co-infected cohort was 7.2%. The quality of evidence supporting this estimate is very low, indicating uncertainty in these estimates of effect. Based on a combined HIV+/HCV+ cohort (n=57) the rate of acute graft rejection does not differ to that of an HCV+ mono-infected cohort (OR: 0.88; 95% CI: 0.44, 1.76). Also based on a combined HIV+/HCV+ cohort (n=83), the rate of HCV+ recurrence does not differ to that of an HCV+ mono-infected cohort (OR: 0.66; 95% CI: 0.27, 1.59). In both cases, the quality of the supporting evidence was very low. Overall, because of very low quality evidence there is uncertainty in the effect of kidney or liver transplantation in HIV+ persons with end stage organ failure compared with those not infected with HIV. Examining the economics of this issue, the cost of kidney and liver transplants in an HIV+ patient population are, on average, 56K and 147K per case, based on both Canadian and American experiences.

Kidney and liver organ transplantation in persons with human immunodeficiency virus

PubMed Central

2010-01-01

Executive Summary Objective The objective of this analysis is to determine the effectiveness of solid organ transplantation in persons with end stage organ failure (ESOF) and human immunodeficiency virus (HIV+) Clinical Need: Condition and Target Population Patients with end stage organ failure who have been unresponsive to other forms of treatment eventually require solid organ transplantation. Similar to persons who are HIV negative (HIV−), persons living with HIV infection (HIV+) are at risk for ESOF from viral (e.g. hepatitis B and C) and non-viral aetiologies (e.g. coronary artery disease, diabetes, hepatocellular carcinoma). Additionally, HIV+ persons also incur risks of ESOF from HIV-associated nephropathy (HIVAN), accelerated liver damage from hepatitis C virus (HCV+), with which an estimated 30% of HIV positive (HIV+) persons are co-infected, and coronary artery disease secondary to antiretroviral therapy. Concerns that the need for post transplant immunosuppression and/or the interaction of immunosuppressive drugs with antiretroviral agents may accelerate the progression of HIV disease, as well as the risk of opportunistic infections post transplantation, have led to uncertainty regarding the overall benefit of transplantation among HIV+ patients. Moreover, the scarcity of donor organs and their use in a population where the clinical benefit of transplantation is uncertain has limited the availability of organ transplantation to persons living with ESOF and HIV. With the development of highly active anti retroviral therapy (HAART), which has been available in Canada since 1997, there has been improved survival and health-related quality of life for persons living with HIV. HAART can suppress HIV replication, enhance immune function, and slow disease progression. HAART managed persons can now be expected to live longer than those in the pre-HAART era and as a result many will now experience ESOF well before they experience life-threatening conditions related to HIV infection. Given their improved prognosis and the burden of illness they may experience from ESOF, the benefit of solid organ transplantation for HIV+ patients needs to be reassessed. Evidence-Based Analysis Methods Research Questions What are the effectiveness and cost effectiveness of solid organ transplantation in HIV+ persons with ESOF? Literature Search A literature search was performed on September 22, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 1996 to September 22, 2009. Inclusion Criteria Systematic review with or without a Meta analysis, RCT, Non-RCT with controls HIV+ population undergoing solid organ transplantation HIV+ population managed with HAART therapy Controls include persons undergoing solid organ transplantation who are i) HIV− ii) HCV+ mono-infected, and iii) HIV+ persons with ESOF not transplanted. Studies that completed and reported results of a Kaplan-Meier Survival Curve analysis. Studies with a minimum (mean or medium) follow up of 1-year. English language citations Exclusion Criteria Case reports and case series were excluded form this review. Outcomes of Interest i) Risk of Death after transplantation ii) Death censored graft survival (DCGS) iii) HIV disease progression defined as the post transplant incidence of: - opportunistic infections or neoplasms, - CD4+ T-cell count < 200mm3, and - any detectable level of plasma HIV viral load. iv) Acute graft rejection, v) Return to dialysis, vi) Recurrence of HCV infection Summary of Findings No direct evidence comparing an HIV+ cohort undergoing transplantation with the same not undergoing transplantation (wait list) was found in the literature search. The results of this review are reported for the following comparison cohorts undergoing transplantation: i) Kidney Transplantation: HIV+ cohort compared with HIV− cohort ii) Liver Transplantation: HIV+ cohort compared with HIV− negative cohort iii) Liver Transplantation: HIV+ HCV+ (co-infected) cohort compared with HCV+ (mono-infected) cohort Kidney Transplantation: HIV+ vs. HIV− Based on a pooled HIV+ cohort sample size of 285 patients across four studies, the risk of death after kidney transplantation in an HIV+ cohort does not differ to that of an HIV− cohort [hazard ratio (HR): 0.90; 95% CI: 0.36, 2.23]. The quality of evidence supporting this outcome is very low. Death censored graft survival was reported in one study with an HIV+ cohort sample size of 100, and was statistically significantly different (p=.03) to that in the HIV− cohort (n=36,492). However, the quality of evidence supporting this outcome was determined to be very low. There was also uncertainty in the rate of return to dialysis after kidney transplantation in both the HIV+ and HIV− groups and the effect, if any, this may have on patient survival. Because of the very low quality evidence rating, the effect of kidney transplantation on HIV-disease progression is uncertain. The rate of acute graft rejection was determined using the data from one study. There was a nonsignificant difference between the HIV+ and HIV− cohorts (OR 0.13; 95% CI: 0.01, 2.64), although again, because of very low quality evidence there is uncertainty in this estimate of effect. Liver Transplantation: HIV+ vs. HIV− Based on a combined HIV+ cohort sample size of 198 patient across five studies, the risk of death after liver transplantation in an HIV+ cohort (with at least 50% of the cohort co-infected with HCV+) is statistically significantly 64% greater compared with an HIV− cohort (HR: 1.64; 95% CI: 1.32, 2.02). The quality of evidence supporting this outcome is very low. Death censored graft survival was reported for an HIV+ cohort in one study (n=11) however the DCGS rate of the contemporaneous control HIV− cohort was not reported. Because of sparse data the quality of evidence supporting this outcome is very low indicating death censored graft survival is uncertain. Both the CD4+ T-cell count and HIV viral load appear controlled post transplant with an incidence of opportunistic infection of 20.5%. However, the quality of this evidence for these outcomes is very low indicating uncertainty in these effects. Similarly, because of very low quality evidence there is uncertainty in the rate of acute graft rejection among both the HIV+ and HIV− groups Liver Transplantation: HIV+/HCV+ vs. HCV+ Based on a combined HIV+/HCV+ cohort sample size of 156 from seven studies, the risk of death after liver transplantation is significantly greater (2.8 fold) in a co-infected cohort compared with an HCV+ mono-infected cohort (HR: 2.81; 95% CI: 1.47, 5.37). The quality of evidence supporting this outcome is very low. Death censored graft survival evidence was not available. Regarding disease progression, based on a combined sample size of 71 persons in the co-infected cohort, the CD4+ T-cell count and HIV viral load appear controlled post transplant; however, again the quality of evidence supporting this outcome is very low. The rate of opportunistic infection in the co-infected cohort was 7.2%. The quality of evidence supporting this estimate is very low, indicating uncertainty in these estimates of effect. Based on a combined HIV+/HCV+ cohort (n=57) the rate of acute graft rejection does not differ to that of an HCV+ mono-infected cohort (OR: 0.88; 95% CI: 0.44, 1.76). Also based on a combined HIV+/HCV+ cohort (n=83), the rate of HCV+ recurrence does not differ to that of an HCV+ mono-infected cohort (OR: 0.66; 95% CI: 0.27, 1.59). In both cases, the quality of the supporting evidence was very low. Overall, because of very low quality evidence there is uncertainty in the effect of kidney or liver transplantation in HIV+ persons with end stage organ failure compared with those not infected with HIV. Examining the economics of this issue, the cost of kidney and liver transplants in an HIV+ patient population are, on average, 56K and 147K per case, based on both Canadian and American experiences. PMID:23074407

Radiation exposure due to local fallout from Soviet atmospheric nuclear weapons testing in Kazakhstan: solid cancer mortality in the Semipalatinsk historical cohort, 1960-1999.

PubMed

Bauer, Susanne; Gusev, Boris I; Pivina, Ludmila M; Apsalikov, Kazbek N; Grosche, Bernd

2005-10-01

Little information is available on the health effects of exposures to fallout from Soviet nuclear weapons testing and on the combined external and internal environmental exposures that have resulted from these tests. This paper reports the first analysis of the Semipalatinsk historical cohort exposed in the vicinity of the Semipalatinsk nuclear test site, Kazakhstan. The cohort study, which includes 19,545 inhabitants of exposed and comparison villages of the Semipalatinsk region, was set up in the 1960s and comprises 582,750 person-years of follow-up between 1960 and 1999. Cumulative effective radiation dose estimates in this cohort range from 20 mSv to approximately 4 Sv. Rates of mortality and cancer mortality in the exposed group substantially exceeded those of the comparison group. Dose-response analyses within the exposed group confirmed a significant trend with dose for all solid cancers (P < 0.0001) and for digestive and respiratory cancers (P = 0.0255 and P < 0.0001), whereas no consistent dose-response trend was found for all causes of death (P = 0.4296). Regarding specific cancer sites, a significant trend with dose was observed for lung cancer (P = 0.0001), stomach cancer (P = 0.0050), and female breast cancer (P = 0.0040) as well as for esophagus cancer in women (P = 0.0030). The excess relative risk per sievert for all solid cancers combined was 1.77 (1.35; 2.27) based on the total cohort data, yet a selection bias regarding the comparison group could not be entirely ruled out. The excess relative risk per sievert based on the cohort's exposed group was 0.81 (0.46; 1.33) for all solid cancers combined and thus still exceeds current risk estimates from the Life Span Study. Future epidemiological assessments based on this cohort will benefit from extension of follow-up and ongoing validation of dosimetric data.

Primary Sjogren's syndrome and the risk of acute pancreatitis: a nationwide cohort study.

PubMed

Chang, Chi-Ching; Chang, Yu-Sheng; Wang, Shu-Hung; Lin, Shyr-Yi; Chen, Yi-Hsuan; Chen, Jin Hua

2017-08-11

Studies on the risk of acute pancreatitis in patients with primary Sjogren's syndrome (pSS) are limited. We evaluated the effects of pSS on the risk of acute pancreatitis in a nationwide, population-based cohort in Taiwan. Population-based retrospective cohort study. We studied the claims data of the >97% Taiwan population from 2002 to 2012. We identified 9468 patients with pSS by using the catastrophic illness registry of the National Health Insurance Database in Taiwan. We also selected 37 872 controls that were randomly frequency matched by age (in 5 year bands), sex and index year from the general population. We analysed the risk of acute pancreatitis by using Cox proportional hazards regression models including sex, age and comorbidities. From 23.74 million people in the cohort, 9468 patients with pSS (87% women, mean age=55.6 years) and 37 872 controls were followed-up for 4.64 and 4.74 years, respectively. A total of 44 cases of acute pancreatitis were identified in the pSS cohort versus 105 cases in the non-pSS cohort. Multivariate Cox regression analysis indicated that the incidence rate of acute pancreatitis was significantly higher in the pSS cohort than in the non-pSS cohort (adjusted HR (aHR) 1.48, 95% CI 1.03 to 2.12). Cyclophosphamide use increased the risk of acute pancreatitis (aHR 5.27, 95% CI 1.16 to 23.86). By contrast, hydroxychloroquine reduced the risk of acute pancreatitis (aHR 0.23, 95% CI 0.09 to 0.55). This nationwide, retrospective cohort study demonstrated that the risk of acute pancreatitis was significantly higher in patients with pSS than in the general population. © 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.

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.

Nonparametric evaluation of birth cohort trends in disease rates.

PubMed

Tarone, R E; Chu, K C

2000-01-01

Although interpretation of age-period-cohort analyses is complicated by the non-identifiability of maximum likelihood estimates, changes in the slope of the birth-cohort effect curve are identifiable and have potential aetiologic significance. A nonparametric test for a change in the slope of the birth-cohort trend has been developed. The test is a generalisation of the sign test and is based on permutational distributions. A method for identifying interactions between age and calendar-period effects is also presented. The nonparametric method is shown to be powerful in detecting changes in the slope of the birth-cohort trend, although its power can be reduced considerably by calendar-period patterns of risk. The method identifies a previously unidentified decrease in the birth-cohort risk of lung-cancer mortality from 1912 to 1919, which appears to reflect a reduction in the initiation of smoking by young men at the beginning of the Great Depression (1930s). The method also detects an interaction between age and calendar period in leukemia mortality rates, reflecting the better response of children to chemotherapy. The proposed nonparametric method provides a data analytic approach, which is a useful adjunct to log-linear Poisson analysis of age-period-cohort models, either in the initial model building stage, or in the final interpretation stage.

Reliability of dose volume constraint inference from clinical data.

PubMed

Lutz, C M; Møller, D S; Hoffmann, L; Knap, M M; Alber, M

2017-04-21

Dose volume histogram points (DVHPs) frequently serve as dose constraints in radiotherapy treatment planning. An experiment was designed to investigate the reliability of DVHP inference from clinical data for multiple cohort sizes and complication incidence rates. The experimental background was radiation pneumonitis in non-small cell lung cancer and the DVHP inference method was based on logistic regression. From 102 NSCLC real-life dose distributions and a postulated DVHP model, an 'ideal' cohort was generated where the most predictive model was equal to the postulated model. A bootstrap and a Cohort Replication Monte Carlo (CoRepMC) approach were applied to create 1000 equally sized populations each. The cohorts were then analyzed to establish inference frequency distributions. This was applied to nine scenarios for cohort sizes of 102 (1), 500 (2) to 2000 (3) patients (by sampling with replacement) and three postulated DVHP models. The Bootstrap was repeated for a 'non-ideal' cohort, where the most predictive model did not coincide with the postulated model. The Bootstrap produced chaotic results for all models of cohort size 1 for both the ideal and non-ideal cohorts. For cohort size 2 and 3, the distributions for all populations were more concentrated around the postulated DVHP. For the CoRepMC, the inference frequency increased with cohort size and incidence rate. Correct inference rates  >[Formula: see text] were only achieved by cohorts with more than 500 patients. Both Bootstrap and CoRepMC indicate that inference of the correct or approximate DVHP for typical cohort sizes is highly uncertain. CoRepMC results were less spurious than Bootstrap results, demonstrating the large influence that randomness in dose-response has on the statistical analysis.

Reliability of dose volume constraint inference from clinical data

NASA Astrophysics Data System (ADS)

Lutz, C. M.; Møller, D. S.; Hoffmann, L.; Knap, M. M.; Alber, M.

2017-04-01

Dose volume histogram points (DVHPs) frequently serve as dose constraints in radiotherapy treatment planning. An experiment was designed to investigate the reliability of DVHP inference from clinical data for multiple cohort sizes and complication incidence rates. The experimental background was radiation pneumonitis in non-small cell lung cancer and the DVHP inference method was based on logistic regression. From 102 NSCLC real-life dose distributions and a postulated DVHP model, an ‘ideal’ cohort was generated where the most predictive model was equal to the postulated model. A bootstrap and a Cohort Replication Monte Carlo (CoRepMC) approach were applied to create 1000 equally sized populations each. The cohorts were then analyzed to establish inference frequency distributions. This was applied to nine scenarios for cohort sizes of 102 (1), 500 (2) to 2000 (3) patients (by sampling with replacement) and three postulated DVHP models. The Bootstrap was repeated for a ‘non-ideal’ cohort, where the most predictive model did not coincide with the postulated model. The Bootstrap produced chaotic results for all models of cohort size 1 for both the ideal and non-ideal cohorts. For cohort size 2 and 3, the distributions for all populations were more concentrated around the postulated DVHP. For the CoRepMC, the inference frequency increased with cohort size and incidence rate. Correct inference rates  >85 % were only achieved by cohorts with more than 500 patients. Both Bootstrap and CoRepMC indicate that inference of the correct or approximate DVHP for typical cohort sizes is highly uncertain. CoRepMC results were less spurious than Bootstrap results, demonstrating the large influence that randomness in dose-response has on the statistical analysis.

Impact of Month of Birth on the Risk of Development of Autoimmune Addison's Disease.

PubMed

Pazderska, Agnieszka; Fichna, Marta; Mitchell, Anna L; Napier, Catherine M; Gan, Earn; Ruchała, Marek; Santibanez-Koref, Mauro; Pearce, Simon H

2016-11-01

The pathogenesis of autoimmune Addison's disease (AAD) is thought to be due to interplay of genetic, immune, and environmental factors. A month-of-birth effect, with increased risk for those born in autumn/winter months, has been described in autoimmune conditions such as type 1 diabetes and autoimmune thyroid disease. Month-of-birth effect was investigated in 2 independent cohorts of AAD subjects. The monthly distribution of birth in AAD patients was compared with that of the general population using the cosinor test. A total of 415 AAD subjects from the United Kingdom cohort were compared with 8 180 180 United Kingdom births, and 231 AAD subjects from the Polish cohort were compared with 2 421 384 Polish births. Association between month of birth and the susceptibility to AAD. In the entire cohort of AAD subjects, month-of-birth distribution analysis showed significant periodicity with peak of births in December and trough in May (P = .028). Analysis of the odds ratio distribution based on month of birth in 2 cohorts of patients with AAD versus the general population revealed a December peak and May trough, and January peak and July trough, in the United Kingdom and Polish cohorts, respectively. For the first time, we demonstrate that month of birth exerts an effect on the risk of developing AAD, with excess risk in individuals born in winter months and a protective effect when born in the summer. Exposure to seasonal viral infections in the perinatal period, coupled with vitamin D deficiency, could lead to dysregulation of innate immunity affecting the risk of developing AAD.

Genetic associations with childhood brain growth, defined in two longitudinal cohorts.

PubMed

Szekely, Eszter; Schwantes-An, Tae-Hwi Linus; Justice, Cristina M; Sabourin, Jeremy A; Jansen, Philip R; Muetzel, Ryan L; Sharp, Wendy; Tiemeier, Henning; Sung, Heejong; White, Tonya J; Wilson, Alexander F; Shaw, Philip

2018-06-01

Genome-wide association studies (GWASs) are unraveling the genetics of adult brain neuroanatomy as measured by cross-sectional anatomic magnetic resonance imaging (aMRI). However, the genetic mechanisms that shape childhood brain development are, as yet, largely unexplored. In this study we identify common genetic variants associated with childhood brain development as defined by longitudinal aMRI. Genome-wide single nucleotide polymorphism (SNP) data were determined in two cohorts: one enriched for attention-deficit/hyperactivity disorder (ADHD) (LONG cohort: 458 participants; 119 with ADHD) and the other from a population-based cohort (Generation R: 257 participants). The growth of the brain's major regions (cerebral cortex, white matter, basal ganglia, and cerebellum) and one region of interest (the right lateral prefrontal cortex) were defined on all individuals from two aMRIs, and a GWAS and a pathway analysis were performed. In addition, association between polygenic risk for ADHD and brain growth was determined for the LONG cohort. For white matter growth, GWAS meta-analysis identified a genome-wide significant intergenic SNP (rs12386571, P = 9.09 × 10 -9 ), near AKR1B10. This gene is part of the aldo-keto reductase superfamily and shows neural expression. No enrichment of neural pathways was detected and polygenic risk for ADHD was not associated with the brain growth phenotypes in the LONG cohort that was enriched for the diagnosis of ADHD. The study illustrates the use of a novel brain growth phenotype defined in vivo for further study. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Associations between excessive adiposity and seroprevalence of herpes simplex virus type 1 and type 2 among US adults: a population-based age-period-cohort analysis.

PubMed

Liu, Su-Hsun; Tzeng, I-Shiang; Hsieh, Tsung-Han; Huang, Yhu-Chering

2016-10-17

Evidence on the association between herpes simplex virus (HSV) and excessive adiposity, such as obesity (body mass index ≥30 kg/m 2 ) and abdominal obesity (waist circumference (WC) >102 or 88 cm), has been inconsistent. We sought to examine whether age-period-cohort (APC) effects could explain for the observed heterogeneities. Population-based cross-sectional study. Adults aged 20-49 years with available serological data in the National Health and Nutrition Examination Survey (NHANES) in 1999-2012. Obesity and abdominal obesity. In men, excessive adiposity was generally not associated with HSV1 or HSV2 (all p>0.05); however, there were positive correlations between HSV seroprevalence and excessive adiposity in certain age and birth cohort groups. Based on APC analysis, abdominally obese men aged 30-40 years showed a nearly 20% increase in risk for HSV1 seropositivity (adjusted prevalence ratio (aPR)=1.18; 95% CI 1.10 to 1.27) as compared with abdominally non-obese men of the same age; there was no such association in men of other age groups. Also, men of a large WC who were born before 1962 or after 1979 had a 28% higher risk for HSV2 seropositivity than those of a normal WC in the same birth cohorts (aPR=1.28, 95% CI 1.17 to 1.54); yet the association did not hold for men in other cohorts (aPR=0.86, 95% CI 0.64 to 1.17). In women, a large WC was correlated with a minimally increased HSV1 seroprevalence (aPR=1.07, 95% CI 1.01 to 1.13) but not with HSV2 seropositivity (aPR=1.13; 95% CI 0.99 to 1.28). Likewise, there were strong associations between abdominal obesity and HSV2 seropositivity in subgroups of women participating in the earliest survey cycle (aPR=1.41, 95% CI 1.12 to 1.78) but not in other survey periods (aPR=0.94, 95% CI 0.85 to 1.03). There was no consistent evidence for strong associations between HSV seropositivity and excessive adiposity in adults. APC analysis results further cautioned the generalisability of previous reports based on 1 or 2 cycles of survey data. 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/.

Associations between excessive adiposity and seroprevalence of herpes simplex virus type 1 and type 2 among US adults: a population-based age–period–cohort analysis

PubMed Central

Tzeng, I-Shiang; Hsieh, Tsung-Han; Huang, Yhu-Chering

2016-01-01

Objectives Evidence on the association between herpes simplex virus (HSV) and excessive adiposity, such as obesity (body mass index ≥30 kg/m2) and abdominal obesity (waist circumference (WC) >102 or 88 cm), has been inconsistent. We sought to examine whether age–period–cohort (APC) effects could explain for the observed heterogeneities. Design Population-based cross-sectional study. Participants Adults aged 20–49 years with available serological data in the National Health and Nutrition Examination Survey (NHANES) in 1999–2012. Exposure measures Obesity and abdominal obesity. Results In men, excessive adiposity was generally not associated with HSV1 or HSV2 (all p>0.05); however, there were positive correlations between HSV seroprevalence and excessive adiposity in certain age and birth cohort groups. Based on APC analysis, abdominally obese men aged 30–40 years showed a nearly 20% increase in risk for HSV1 seropositivity (adjusted prevalence ratio (aPR)=1.18; 95% CI 1.10 to 1.27) as compared with abdominally non-obese men of the same age; there was no such association in men of other age groups. Also, men of a large WC who were born before 1962 or after 1979 had a 28% higher risk for HSV2 seropositivity than those of a normal WC in the same birth cohorts (aPR=1.28, 95% CI 1.17 to 1.54); yet the association did not hold for men in other cohorts (aPR=0.86, 95% CI 0.64 to 1.17). In women, a large WC was correlated with a minimally increased HSV1 seroprevalence (aPR=1.07, 95% CI 1.01 to 1.13) but not with HSV2 seropositivity (aPR=1.13; 95% CI 0.99 to 1.28). Likewise, there were strong associations between abdominal obesity and HSV2 seropositivity in subgroups of women participating in the earliest survey cycle (aPR=1.41, 95% CI 1.12 to 1.78) but not in other survey periods (aPR=0.94, 95% CI 0.85 to 1.03). Conclusions There was no consistent evidence for strong associations between HSV seropositivity and excessive adiposity in adults. APC analysis results further cautioned the generalisability of previous reports based on 1 or 2 cycles of survey data. PMID:27798014

Use of fertility drugs and risk of ovarian cancer: Danish Population Based Cohort Study.

PubMed

Jensen, Allan; Sharif, Heidi; Frederiksen, Kirsten; Kjaer, Susanne Krüger

2009-02-05

To examine the effects of fertility drugs on overall risk of ovarian cancer using data from a large cohort of infertile women. Population based cohort study. Danish hospitals and private fertility clinics. 54,362 women with infertility problems referred to all Danish fertility clinics during 1963-98. The median age at first evaluation of infertility was 30 years (range 16-55 years), and the median age at the end of follow-up was 47 (range 18-81) years. Included in the analysis were 156 women with invasive epithelial ovarian cancer (cases) and 1241 subcohort members identified in the cohort during follow-up in 2006. Effect of four groups of fertility drugs (gonadotrophins, clomifene citrate, human chorionic gonadotrophin, and gonadotrophin releasing hormone) on overall risk of ovarian cancer after adjustment for potential confounding factors. Analyses within cohort showed no overall increased risk of ovarian cancer after any use of gonadotrophins (rate ratio 0.83, 95% confidence interval 0.50 to 1.37), clomifene (1.14, 0.79 to 1.64), human chorionic gonadotrophin (0.89, 0.62 to 1.29), or gonadotrophin releasing hormone (0.80, 0.42 to 1.51). Furthermore, no associations were found between all four groups of fertility drugs and number of cycles of use, length of follow-up, or parity. No convincing association was found between use of fertility drugs and risk of ovarian cancer.

Introducing laparoscopic total gastrectomy for gastric cancer in general practice: a retrospective cohort study based on a nationwide registry database in Japan.

PubMed

Kodera, Yasuhiro; Yoshida, Kazuhiro; Kumamaru, Hiraku; Kakeji, Yoshihiro; Hiki, Naoki; Etoh, Tsuyoshi; Honda, Michitaka; Miyata, Hiroaki; Yamashita, Yuichi; Seto, Yasuyuki; Kitano, Seigo; Konno, Hiroyuki

2018-02-09

Although laparoscopic total gastrectomy (LTG) is considered a technically demanding procedure with safety issues, it has been performed in several hospitals in Japan. Data from a nationwide web-based data entry system for surgical procedures (NCD) that started enrollment in 2011 are now available for analysis. A retrospective cohort study was conducted using data from 32,144 patients who underwent total gastrectomy and were registered in the NCD database between January 2012 and December 2013. Mortality and morbidities were compared between patients who received LTG and those who underwent open total gastrectomy (OTG) in the propensity score-matched Stage I cohort and Stage II-IV cohort. There was no significant difference in mortality rate between LTG and OTG in both cohorts. Operating time was significantly longer in LTG while the blood loss was smaller. In the Stage I cohort, LTG, performed in 33.6% of the patients, was associated with significantly shorter hospital stay but significantly higher incidence of readmission, reoperation, and anastomotic leakage (5.4% vs. 3.6%, p < 0.01). In the Stage II-IV cohort, LTG was performed in only 8.8% of the patients and was associated with significantly higher incidence of leakage (5.7% vs. 3.6%, p < 0.02) although the hospital stay was shorter (15 days vs. 17 days, p < 0.001). LTG was more discreetly introduced than distal gastrectomy, but remained a technically demanding procedure as of 2013. This procedure should be performed only among the well-trained and informed laparoscopic team.

Esophagus cancer and radiation exposure due to nuclear test fallout: an analysis based on the data of the Semipalatinsk historical cohort, 1960-1999.

PubMed

Bauer, S; Gusev, B I; Pivina, L M; Apsalikov, K N; Grosche, B

2006-01-01

This paper describes the Semipalatinsk historical cohort study and, in particular, examines the association between combined external and internal radiation exposure and esophagus cancer. Esophagus cancer is the most frequent single cancer site in the cause of death follow-up for the Semipalatinsk cohort. Set up in the 1960s, this historical cohort included 10 exposed settlements in the vicinity of the Semipalatinsk nuclear test site in East Kazakhstan as well as 6 comparison settlements in a low exposure area of the same region. The external and internal radiation doses to the population of the settlements under study were mainly due to local fallout from atmospheric nuclear testing (1949-1962). The database includes dosimetry and health information for 19.545 inhabitants of exposed and comparison villages in the Semipalatinsk region, comprising a total of 582.750 person-years of follow-up between 1960 and 1999. Cumulative effective dose estimates in this cohort range from 20 mSv to -4 Sv, with a mean dose of 634 mSv in the exposed group. Relative risks were calculated in terms of rate ratios, using a Poisson regression model for grouped person-time data. Esophagus cancer was found substantially elevated, with a statistically significant increase of the relative risk with dose and an ERR/Sv of 2.37 (1.45; 3.28) for the total cohort. If the data set was restricted to the exposed group only, the ERR/Sv was found considerably lower (0.18 (-0.16; 0.52)), whereas the dose-response remained significant only in women. Overall, our results based on the Semipalatinsk historical cohort indicate an association between fallout exposure and the risk of esophagus cancer that should be further investigated.

Development of an accelerometer-based multivariate model to predict free-living energy expenditure in a large military cohort.

PubMed

Horner, Fleur; Bilzon, James L; Rayson, Mark; Blacker, Sam; Richmond, Victoria; Carter, James; Wright, Anthony; Nevill, Alan

2013-01-01

This study developed a multivariate model to predict free-living energy expenditure (EE) in independent military cohorts. Two hundred and eighty-eight individuals (20.6 ± 3.9 years, 67.9 ± 12.0 kg, 1.71 ± 0.10 m) from 10 cohorts wore accelerometers during observation periods of 7 or 10 days. Accelerometer counts (PAC) were recorded at 1-minute epochs. Total energy expenditure (TEE) and physical activity energy expenditure (PAEE) were derived using the doubly labelled water technique. Data were reduced to n = 155 based on wear-time. Associations between PAC and EE were assessed using allometric modelling. Models were derived using multiple log-linear regression analysis and gender differences assessed using analysis of covariance. In all models PAC, height and body mass were related to TEE (P < 0.01). For models predicting TEE (r (2) = 0.65, SE = 462 kcal · d(-1) (13.0%)), PAC explained 4% of the variance. For models predicting PAEE (r (2) = 0.41, SE = 490 kcal · d(-1) (32.0%)), PAC accounted for 6% of the variance. Accelerometry increases the accuracy of EE estimation in military populations. However, the unique nature of military life means accurate prediction of individual free-living EE is highly dependent on anthropometric measurements.

A preliminary analysis of trace-elemental signatures in statoliths of different spawning cohorts for Dosidicus gigas off EEZ waters of Chile

NASA Astrophysics Data System (ADS)

Liu, Bilin; Chen, Xinjun; Fang, Zhou; Hu, Song; Song, Qian

2015-12-01

We applied solution-based ICP-MS method to quantify the trace-elemental signatures in statoliths of jumbo flying squid, Dosidius gigas, which were collected from the waters off northern and central Chile during the scientific surveys carried out by Chinese squid jigging vessels in 2007 and 2008. The age and spawning date of the squid were back-calculated based on daily increments in statoliths. Eight elemental ratios (Sr/Ca, Ba/Ca, Mg/Ca, Mn/Ca, Na/Ca, Fe/Ca, Cu/Ca and Zn/Ca) were analyzed. It was found that Sr is the second most abundant element next to Ca, followed by Na, Fe, Mg, Zn, Cu, Ba and Mn. There was no significant relationship between element/Ca and sea surface temperature (SST) and sea surface salinity (SSS), although weak negative or positive tendency was found. MANOVA analysis showed that multivariate elemental signatures did not differ among the cohorts spawned in spring, autumn and winter, and no significant difference was found between the northern and central sampling locations. Classification results showed that all individuals of each spawned cohorts were correctly classified. This study demonstrates that the elemental signatures in D. gigas statoliths are potentially a useful tool to improve our understanding of its population structure and habitat environment.

What provides a better value for your time? The use of relative value units to compare posterior segmental instrumentation of vertebral segments.

PubMed

Orr, R Douglas; Sodhi, Nipun; Dalton, Sarah E; Khlopas, Anton; Sultan, Assem A; Chughtai, Morad; Newman, Jared M; Savage, Jason; Mroz, Thomas E; Mont, Michael A

2018-02-02

Relative value units (RVUs) are a compensation model based on the effort required to provide a procedure or service to a patient. Thus, procedures that are more complex and require greater technical skill and aftercare, such as multilevel spine surgery, should provide greater physician compensation. However, there are limited data comparing RVUs with operative time. Therefore, this study aims to compare mean (1) operative times; (2) RVUs; and (3) RVU/min between posterior segmental instrumentation of 3-6, 7-12, and ≥13 vertebral segments, and to perform annual cost difference analysis. A total of 437 patients who underwent instrumentation of 3-6 segments (Cohort 1, current procedural terminology [CPT] code: 22842), 67 patients who had instrumentation of 7-12 segments (Cohort 2, CPT code: 22843), and 16 patients who had instrumentation of ≥13 segments (Cohort 3, CPT code: 22844) were identified from the National Surgical Quality Improvement Program (NSQIP) database. Mean operative times, RVUs, and RVU/min, as well as an annualized cost difference analysis, were calculated and compared using Student t test. This study received no funding from any party or entity. Cohort 1 had shorter mean operative times than Cohorts 2 and 3 (217 minutes vs. 325 minutes vs. 426 minutes, p<.05). Cohort 1 had a lower mean RVU than Cohorts 2 and 3 (12.6 vs. 13.4 vs. 16.4). Cohort 1 had a greater RVU/min than Cohorts 2 and 3 (0.08 vs. 0.05, p<.05; vs. 0.08 vs. 0.05, p>.05). A $112,432.12 annualized cost difference between Cohorts 1 and 2, a $176,744.76 difference between Cohorts 1 and 3, and a $64,312.55 difference between Cohorts 2 and 3 were calculated. The RVU/min takes into account not just the value provided but also the operative times required for highly complex cases. The RVU/min for fewer vertebral level instrumentation being greater (0.08 vs. 0.05), as well as the $177,000 annualized cost difference, indicates that compensation is not proportional to the added time, effort, and skill for more complex cases. Copyright © 2018 Elsevier Inc. All rights reserved.

Implementation and impact of a consensus diagnostic and management algorithm for complicated pneumonia in children.

PubMed

Pillai, Dinesh; Song, Xiaoyan; Pastor, William; Ottolini, Mary; Powell, David; Wiedermann, Bernhard L; DeBiasi, Roberta L

2011-12-01

Variable treatment exists for children with bacterial pneumonia complications such as pleural effusion and empyema. Subspecialists at an urban academic tertiary children's hospital created a literature-based diagnosis and management algorithm for complicated pneumonia in children. We proposed that algorithm implementation would reduce use of computed tomography (CT) for diagnosis of pleural infection, thereby decreasing radiation exposure, without increased adverse outcomes. A cross-sectional study was undertaken in children (3 months to 20 years old) with principal or secondary diagnosis codes for empyema and/or pleural effusion in conjunction with bacterial pneumonia. Study cohorts consisted of subjects admitted 15 months before (cohort 1, n = 83) and after (cohort 2, n = 87) algorithm implementation. Data were collected using clinical and financial data systems. Imaging studies and procedures were identified using Current Procedural Terminology codes. Statistical analysis included χ test, linear and ordinal regression, and analysis of variance. Age (P = 0.56), sex (P = 0.30), diagnoses (P = 0.12), and severity level (P = 0.84) were similar between cohorts. There was a significant decrease in CT use in cohort 2 (cohort 1, 60% vs cohort 2, 17.2%; P = 0.001) and reduction in readmission rate (7.7% vs 0%; P = 0.01) and video-assisted thoracoscopic surgery procedures (44.6% vs 28.7; P = 0.03), without concomitant increases in vancomycin use (34.9% vs 34.5%; P = 0.95) or hospital length of stay (6.4 vs 7.6 days; P = 0.4). Among patients who received video-assisted thoracoscopic surgery drainage (n = 57), there were no significant differences between cohorts in median time from admission to video-assisted thoracoscopic surgery (2 days; P = 0.29) or median duration of chest tube drainage (3 vs 4 days; P = 0.10). There was a statistically nonsignificant trend for higher rate of pathogen identification in cohort 2 (cohort 1, 33% vs cohort 2, 54.1%; P = 0.12); Streptococcus pneumonia was the most commonly identified pathogen in both cohorts (37.5% vs 27%; P = 0.23). Implementation of an institutional complicated pneumonia management algorithm reduced CT scan use/radiation exposure, VATS procedures, and readmission rate in children with a diagnosis of pleural infection, without associated increases in length of stay or vancomycin use. This algorithm provides the framework for future prospective quality improvement studies in pediatric patients with complicated pneumonia.

Understanding the Disease Course and Therapeutic Benefit of Tafamidis Across Real-World Studies of Hereditary Transthyretin Amyloidosis with Polyneuropathy: A Proof of Concept for Integrative Data Analytic Approaches.

PubMed

Serrano, Daniel; Atzinger, Christopher B; Botteman, Marc F

2018-06-01

Hereditary transthyretin (TTR) amyloidosis with polyneuropathy (hATTR-PN) is a rare, autosomal dominant amyloidosis characterized primarily by progressive ascending sensorimotor neuropathy often associated with  autonomic involvement. hATTR-PN is caused by a mutation in the TTR gene leading to protein misfolding and amyloid accumulation in peripheral nerves and vital organs. The latest global prevalence estimates point to 10,000 cases worldwide, with an upper end of about 40,000. Tafamidis has been approved in over 40 countries for delaying neurologic disease progression in early-stage hATTR-PN. Multiple observational studies have examined clinical outcomes in hATTR-PN patients treated with tafamidis in the routine clinical setting. Integrative data analysis (IDA) is a technique for optimally constructing synthetic treatment and control cohorts from multiple independent studies, which allows meta-analysis of patient-level data. Herein, we provide a proof of concept for the application of IDA to real-world and natural history hATTR-PN data. IDA permits increased understanding of outcomes in tafamidis-treated and untreated persons with hATTR-PN by optimally pooling all available information. Summary statistics corresponding to the Neuropathy Impairment Score-Lower Limb (NIS-LL) from five published studies were pooled, converted to change from baseline means and variances, and analyzed using IDA. IDA-based synthetic cohorts were generated by averaging across studies stratified on treatment versus control cohort. Trends in change from baseline in each study and the corresponding synthetic cohorts were plotted. Patient-level data were simulated from the synthetic cohort trends in a Monte Carlo simulation to highlight the ability to contrast synthetic cohort trends using the mixed model for repeated measures (MMRM). The average sample size among the five studies was 71 (37-128) patients. The average NIS-LL trends indicated that tafamidis-treated patients experienced slower progression in neuropathy compared to untreated patients. Synthetic cohort trends reflected the trends observed in the contributing studies, while simultaneously shrinking the width of corresponding confidence bands. Monte Carlo simulation results demonstrated precise recovery of the synthetic cohort and time-dependent simulated NIS-LL means by the MMRM. This proof of concept demonstrates the utility of IDA-based synthetic cohorts for increased precision in characterizing and testing hypotheses about treatment outcomes and prognosis in hATTR-PN. Pfizer. Plain language summary available for this article.

Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

PubMed Central

Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo; Yokoyama, Yoshie; Siribaddana, Sisira H; Hotopf, Matthew; Sumathipala, Athula; Rijsdijk, Fruhling; Tan, Qihua; Zhang, Dongfeng; Pang, Zengchang; Aaltonen, Sari; Heikkilä, Kauko; Öncel, Sevgi Y; Aliev, Fazil; Rebato, Esther; Tarnoki, Adam D; Tarnoki, David L; Christensen, Kaare; Skytthe, Axel; Kyvik, Kirsten O; Silberg, Judy L; Eaves, Lindon J; Maes, Hermine H; Cutler, Tessa L; Hopper, John L; Ordoñana, Juan R; Sánchez-Romera, Juan F; Colodro-Conde, Lucia; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Sung, Joohon; Song, Yun-Mi; Yang, Sarah; Lee, Kayoung; Franz, Carol E; Kremen, William S; Lyons, Michael J; Busjahn, Andreas; Nelson, Tracy L; Whitfield, Keith E; Kandler, Christian; Jang, Kerry L; Gatz, Margaret; Butler, David A; Stazi, Maria A; Fagnani, Corrado; D'Ippolito, Cristina; Duncan, Glen E; Buchwald, Dedra; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth JF; Martin, Nicholas G; Medland, Sarah E; Montgomery, Grant W; Jeong, Hoe-Uk; Swan, Gary E; Krasnow, Ruth; Magnusson, Patrik KE; Pedersen, Nancy L; Dahl-Aslan, Anna K; McAdams, Tom A; Eley, Thalia C; Gregory, Alice M; Tynelius, Per; Baker, Laura A; Tuvblad, Catherine; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Lichtenstein, Paul; Spector, Timothy D; Mangino, Massimo; Lachance, Genevieve; Bartels, Meike; van Beijsterveldt, Toos CEM; Willemsen, Gonneke; Burt, S Alexandra; Klump, Kelly L; Harris, Jennifer R; Brandt, Ingunn; Nilsen, Thomas Sevenius; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Corley, Robin P; Hjelmborg, Jacob v B; Goldberg, Jack H; Iwatani, Yoshinori; Watanabe, Mikio; Honda, Chika; Inui, Fujio; Rasmussen, Finn; Huibregtse, Brooke M; Boomsma, Dorret I; Sørensen, Thorkild I A; Kaprio, Jaakko; Silventoinen, Karri

2016-01-01

Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886–1994. Although genetic variance showed a generally increasing trend across the birth-year cohorts, heritability estimates (0.69-0.84 in men and 0.53-0.78 in women) did not present any clear pattern of secular changes. Comparing geographic-cultural regions (Europe, North America and Australia, and East Asia), total height variance was greatest in North America and Australia and lowest in East Asia, but no clear pattern in the heritability estimates across the birth-year cohorts emerged. Our findings do not support the hypothesis that heritability of height is lower in populations with low living standards than in affluent populations, nor that heritability of height will increase within a population as living standards improve. DOI: http://dx.doi.org/10.7554/eLife.20320.001 PMID:27964777

Associations of rotational shift work and night shift status with hypertension: a systematic review and meta-analysis.

PubMed

Manohar, Sandhya; Thongprayoon, Charat; Cheungpasitporn, Wisit; Mao, Michael A; Herrmann, Sandra M

2017-10-01

The reported risks of hypertension (HTN) in rotating shift and night shift workers are controversial. The objective of this meta-analysis was to assess the association between shift work status and HTN. A literature search was performed using MEDLINE, EMBASE and Cochrane Database from inception through October 2016. Studies that reported odds ratios (OR) comparing the risk of HTN in shift workers were included. A prespecified subgroup analysis by rotating shift and night shift statuses were also performed. Pooled OR and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. The protocol for this study is registered with International Prospective Register of Systematic Reviews; no. CRD42016051843. Twenty-seven observational studies (nine cohort and 18 cross-sectional studies) with a total of 394 793 individuals were enrolled. The pooled ORs of HTN in shift workers in cohort and cross-sectional studies were 1.31 (95% CI, 1.07-1.60) and 1.10 (95% CI, 1.00-1.20), respectively. When meta-analysis was restricted only to cohort studies in rotating shift, the pooled OR of HTN in rotating shift workers was 1.34 (95% CI, 1.08-1.67). The data regarding night shift and HTN in cohort studies was limited. The pooled OR of HTN in night shift workers in cross-sectional studies was 1.07 (95% CI, 0.85-1.35). Based on the findings of our meta-analysis, shiftwork status may play an important role in HTN, as there is a significant association between rotating shift work and HTN. However, there is no significant association between night shift status and risk of HTN.

Risk of community-acquired pneumonia in patients with a diagnosis of pernicious anemia: a population-based retrospective cohort study.

PubMed

Almario, Christopher V; Metz, David C; Haynes, Kevin; Yang, Yu-Xiao

2015-11-01

Pernicious anemia (PA) is an autoimmune disease that causes achlorhydria or profound hypochlorhydria. We conducted a population-based study to determine whether individuals with PA are at an increased risk for community-acquired pneumonia (CAP). We performed a retrospective cohort study using The Health Improvement Network (THIN) from the UK (1993-2009). The eligible study cohort included individuals 18 years of age or older, with at least 1 year of THIN follow-up. The exposed group consisted of individuals with a diagnosis code for PA. The unexposed group consisted of individuals without a diagnosis of PA and was frequency matched with the exposed group with respect to age, sex, and practice site. Cox regression analysis was used to determine the hazard ratio with the 95% confidence interval for CAP associated with PA, accounting for a comprehensive list of potential confounders. The study included 13,605 individuals with PA and 50,586 non-PA individuals. The crude incidence rate of CAP was 9.4/1000 person-years for those with PA, versus 6.4/1000 person-years for those without PA. The multivariable adjusted hazard ratio for CAP associated with PA was 1.18 (95% confidence interval 1.08-1.29). In this large population-based cohort study, individuals with PA and presumed chronic achlorhydria were at an increased risk for CAP.

Quantifying the dose-response relationship between circulating folate concentrations and colorectal cancer in cohort studies: a meta-analysis based on a flexible meta-regression model.

PubMed

Chuang, Shu-Chun; Rota, Matteo; Gunter, Marc J; Zeleniuch-Jacquotte, Anne; Eussen, Simone J P M; Vollset, Stein Emil; Ueland, Per Magne; Norat, Teresa; Ziegler, Regina G; Vineis, Paolo

2013-10-01

Most epidemiologic studies on folate intake suggest that folate may be protective against colorectal cancer, but the results on circulating (plasma or serum) folate are mostly inconclusive. We conducted a meta-analysis of case-control studies nested within prospective studies on circulating folate and colorectal cancer risk by using flexible meta-regression models to test the linear and nonlinear dose-response relationships. A total of 8 publications (10 cohorts, representing 3,477 cases and 7,039 controls) were included in the meta-analysis. The linear and nonlinear models corresponded to relative risks of 0.96 (95% confidence interval (CI): 0.91, 1.02) and 0.99 (95% CI: 0.96, 1.02), respectively, per 10 nmol/L of circulating folate in contrast to the reference value. The pooled relative risks when comparing the highest with the lowest category were 0.80 (95% CI: 0.61, 0.99) for radioimmunoassay and 1.03 (95% CI: 0.83, 1.22) for microbiological assay. Overall, our analyses suggest a null association between circulating folate and colorectal cancer risk. The stronger association for the radioimmunoassay-based studies could reflect differences in cohorts and study designs rather than assay performance. Further investigations need to integrate more accurate measurements and flexible modeling to explore the effects of folate in the presence of genetic, lifestyle, dietary, and hormone-related factors.

SMELTING PLANT CADMIUM/ARSENIC EXPOSURE COHORT ANALYSIS

EPA Science Inventory

EPA's proposed IRIS cancer assessment (as well as OSHA, NIOSH and the European Union assessments) classify cadmium as a probable human carcinogen by inhalation exposure, based principally on data from the Globe Manufacturing facility located in the Western U.S. A major confoundi...

Comparison of Estimates between Cohort and Case-Control Studies in Meta-Analyses of Therapeutic Interventions: A Meta-Epidemiological Study.

PubMed

Lanza, Amy; Ravaud, Philippe; Riveros, Carolina; Dechartres, Agnes

2016-01-01

Observational studies are increasingly being used for assessing therapeutic interventions. Case-control studies are generally considered to have greater risk of bias than cohort studies, but we lack evidence of differences in effect estimates between the 2 study types. We aimed to compare estimates between cohort and case-control studies in meta-analyses of observational studies of therapeutic interventions by using a meta-epidemiological study. We used a random sample of meta-analyses of therapeutic interventions published in 2013 that included both cohort and case-control studies assessing a binary outcome. For each meta-analysis, the ratio of estimates (RE) was calculated by comparing the estimate in case-control studies to that in cohort studies. Then, we used random-effects meta-analysis to estimate a combined RE across meta-analyses. An RE < 1 indicated that case-control studies yielded larger estimates than cohort studies. The final analysis included 23 meta-analyses: 138 cohort and 133 case-control studies. Treatment effect estimates did not significantly differ between case-control and cohort studies (combined RE 0.97 [95% CI 0.86-1.09]). Heterogeneity was low, with between-meta-analysis variance τ2 = 0.0049. Estimates did not differ between case-control and prospective or retrospective cohort studies (RE = 1.05 [95% CI 0.96-1.15] and RE = 0.99 [95% CI, 0.83-1.19], respectively). Sensitivity analysis of studies reporting adjusted estimates also revealed no significant difference (RE = 1.03 [95% CI 0.91-1.16]). Heterogeneity was also low for these analyses. We found no significant difference in treatment effect estimates between case-control and cohort studies assessing therapeutic interventions.

Development and validation of an ICD-10-based disability predictive index for patients admitted to hospitals with trauma.

PubMed

Wada, Tomoki; Yasunaga, Hideo; Yamana, Hayato; Matsui, Hiroki; Fushimi, Kiyohide; Morimura, Naoto

2018-03-01

There was no established disability predictive measurement for patients with trauma that could be used in administrative claims databases. The aim of the present study was to develop and validate a diagnosis-based disability predictive index for severe physical disability at discharge using the International Classification of Diseases, 10th revision (ICD-10) coding. This retrospective observational study used the Diagnosis Procedure Combination database in Japan. Patients who were admitted to hospitals with trauma and discharged alive from 01 April 2010 to 31 March 2015 were included. Pediatric patients under 15 years old were excluded. Data for patients admitted to hospitals from 01 April 2010 to 31 March 2013 was used for development of a disability predictive index (derivation cohort), while data for patients admitted to hospitals from 01 April 2013 to 31 March 2015 was used for the internal validation (validation cohort). The outcome of interest was severe physical disability defined as the Barthel Index score of <60 at discharge. Trauma-related ICD-10 codes were categorized into 36 injury groups with reference to the categorization used in the Global Burden of Diseases study 2013. A multivariable logistic regression analysis was performed for the outcome using the injury groups and patient baseline characteristics including patient age, sex, and Charlson Comorbidity Index (CCI) score in the derivation cohort. A score corresponding to a regression coefficient was assigned to each injury group. The disability predictive index for each patient was defined as the sum of the scores. The predictive performance of the index was validated using the receiver operating characteristic curve analysis in the validation cohort. The derivation cohort included 1,475,158 patients, while the validation cohort included 939,659 patients. Of the 939,659 patients, 235,382 (25.0%) were discharged with severe physical disability. The c-statistics of the disability predictive index was 0.795 (95% confidence interval [CI] 0.794-0.795), while that of a model using the disability predictive index and patient baseline characteristics was 0.856 (95% CI 0.855-0.857). Severe physical disability at discharge may be well predicted with patient age, sex, CCI score, and the diagnosis-based disability predictive index in patients admitted to hospitals with trauma. Copyright © 2018 Elsevier Ltd. All rights reserved.

The increase in prescriptions of bisphosphonates and the incidence proportion of osteonecrosis of the jaw after risk communication activities in Japan: a hospital-based cohort study†

PubMed Central

Sumi, Eriko; Yamazaki, Toru; Tanaka, Shiro; Yamamoto, Keiichi; Nakayama, Takeo; Bessho, Kazuhisa; Yokode, Masayuki

2014-01-01

Purpose The purpose of this study was to investigate the impact of risk communication about bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) on the number of reported cases to the Drug Adverse Reactions Reporting System and on the incidence proportion of ONJ in a hospital-based cohort study in Japan. Method We conducted a survey of the safety information on BP-related ONJ available from regulatory authorities, pharmaceutical manufacturers and academic associations. We also performed a trend analysis of a dataset from the Drug Adverse Reactions Reporting System and a sub-analysis, using previously constructed data from a retrospective cohort study. Results Risk communication from pharmaceutical manufacturers and academic associations began within 1 year after revisions were made to the package inserts, in October 2006. Twenty times more cases of ONJ have been reported to regulatory authority since 2007, compared with the period before 2007. In our cohort, the incidence proportion of ONJ during and after 2009 was four times greater than before 2009. During this period, BPs were frequently prescribed, whereas there was no increase in the use of alternative agents, such as selective estrogen receptor modulators. Conclusion ONJ was increasingly diagnosed after risk communication efforts, but the impact of the communications was not clear. Safety notifications were diligently disseminated after the package insert was revised. However, there was no surveillance for ONJ before the revision. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:24399628

Creatinine generation is reduced in patients requiring continuous venovenous hemodialysis and independently predicts mortality

PubMed Central

Wilson, Francis P.; Sheehan, Jessica M.; Mariani, Laura H.; Berns, Jeffrey S.

2012-01-01

Background Existing systems for grading severity of acute kidney injury (AKI) rely on a change of serum creatinine concentration over a defined time interval. The rate of change in serum creatinine increases by degree of reduction in glomerular filtration rate, but is mitigated by low creatinine generation rate (CGR). Failure to appreciate variation in CGR may lead to erroneous conclusions regarding severity of AKI and distorted predictions regarding patient outcomes based on AKI severity. Methods Cohort study of 103 patients who received continuous venovenous hemodialysis (CVVHD) over a 2-year period in a tertiary care hospital setting. Study participants entered the cohort when they were anuric, receiving a stable and uninterrupted dose of CVVHD with serum creatinine in steady state. They were followed until hospital discharge. CGR was measured based on dialyzate effluent volume and effluent creatinine concentration (prospective cohort) and via effluent volume and serum creatinine concentration (retrospective cohort). Results CGR (mean 10.5, range 1.7–22.4 mg/kg/day) was substantially lower in this patient population than what would be predicted from existing equations. Correlates of CGR in multivariable analysis included the length of hospitalization prior to measurement and presence of an oncologic diagnosis. Lower CGR was independently associated with in-hospital mortality in unadjusted analysis and after multivariable adjustment for measures of severity of illness. Conclusions Grading systems for severity of AKI fail to account for variation in CGR, limiting their ability to predict relevant outcomes. Calculation of CGR is superior to other risk metrics in predicting hospital mortality in this population. PMID:22273668

Common Variants within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage

PubMed Central

Anderson, Christopher D.; Biffi, Alessandro; Nalls, Michael A.; Devan, William J.; Schwab, Kristin; Ayres, Alison M.; Valant, Valerie; Ross, Owen A.; Rost, Natalia S.; Saxena, Richa; Viswanathan, Anand; Worrall, Bradford B.; Brott, Thomas G.; Goldstein, Joshua N.; Brown, Devin; Broderick, Joseph P.; Norrving, Bo; Greenberg, Steven M.; Silliman, Scott L.; Hansen, Björn M.; Tirschwell, David L.; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Selim, Magdy; Roquer, Jaume; Montaner, Joan; Singleton, Andrew B.; Kidwell, Chelsea S.; Woo, Daniel; Furie, Karen L.; Meschia, James F.; Rosand, Jonathan

2013-01-01

Background and Purpose Prior studies demonstrated association between mitochondrial DNA variants and ischemic stroke (IS). We investigated whether variants within a larger set of oxidative phosphorylation (OXPHOS) genes encoded by both autosomal and mitochondrial DNA were associated with risk of IS and, based on our results, extended our investigation to intracerebral hemorrhage (ICH). Methods This association study employed a discovery cohort of 1643 individuals, a validation cohort of 2432 individuals for IS, and an extension cohort of 1476 individuals for ICH. Gene-set enrichment analysis (GSEA) was performed on all structural OXPHOS genes, as well as genes contributing to individual respiratory complexes. Gene-sets passing GSEA were tested by constructing genetic scores using common variants residing within each gene. Associations between each variant and IS that emerged in the discovery cohort were examined in validation and extension cohorts. Results IS was associated with genetic risk scores in OXPHOS as a whole (odds ratio (OR)=1.17, p=0.008) and Complex I (OR=1.06, p=0.050). Among IS subtypes, small vessel (SV) stroke showed association with OXPHOS (OR=1.16, p=0.007), Complex I (OR=1.13, p=0.027) and Complex IV (OR 1.14, p=0.018). To further explore this SV association, we extended our analysis to ICH, revealing association between deep hemispheric ICH and Complex IV (OR=1.08, p=0.008). Conclusions This pathway analysis demonstrates association between common genetic variants within OXPHOS genes and stroke. The associations for SV stroke and deep ICH suggest that genetic variation in OXPHOS influences small vessel pathobiology. Further studies are needed to identify culprit genetic variants and assess their functional consequences. PMID:23362085

Sugar-sweetened beverages and weight gain in children and adults: a systematic review and meta-analysis123

PubMed Central

Pan, An; Willett, Walter C; Hu, Frank B

2013-01-01

Background: The relation between sugar-sweetened beverages (SSBs) and body weight remains controversial. Objective: We conducted a systematic review and meta-analysis to summarize the evidence in children and adults. Design: We searched PubMed, EMBASE, and Cochrane databases through March 2013 for prospective cohort studies and randomized controlled trials (RCTs) that evaluated the SSB-weight relation. Separate meta-analyses were conducted in children and adults and for cohorts and RCTs by using random- and fixed-effects models. Results: Thirty-two original articles were included in our meta-analyses: 20 in children (15 cohort studies, n = 25,745; 5 trials, n = 2772) and 12 in adults (7 cohort studies, n = 174,252; 5 trials, n = 292). In cohort studies, one daily serving increment of SSBs was associated with a 0.06 (95% CI: 0.02, 0.10) and 0.05 (95% CI: 0.03, 0.07)-unit increase in BMI in children and 0.22 kg (95% CI: 0.09, 0.34 kg) and 0.12 kg (95% CI: 0.10, 0.14 kg) weight gain in adults over 1 y in random- and fixed-effects models, respectively. RCTs in children showed reductions in BMI gain when SSBs were reduced [random and fixed effects: −0.17 (95% CI: −0.39, 0.05) and −0.12 (95% CI: −0.22, −0.2)], whereas RCTs in adults showed increases in body weight when SSBs were added (random and fixed effects: 0.85 kg; 95% CI: 0.50, 1.20 kg). Sensitivity analyses of RCTs in children showed more pronounced benefits in preventing weight gain in SSB substitution trials (compared with school-based educational programs) and among overweight children (compared with normal-weight children). Conclusion: Our systematic review and meta-analysis of prospective cohort studies and RCTs provides evidence that SSB consumption promotes weight gain in children and adults. PMID:23966427

Sugar-sweetened beverage consumption and genetic predisposition to obesity in 2 Swedish cohorts.

PubMed

Brunkwall, Louise; Chen, Yan; Hindy, George; Rukh, Gull; Ericson, Ulrika; Barroso, Inês; Johansson, Ingegerd; Franks, Paul W; Orho-Melander, Marju; Renström, Frida

2016-09-01

The consumption of sugar-sweetened beverages (SSBs), which has increased substantially during the last decades, has been associated with obesity and weight gain. Common genetic susceptibility to obesity has been shown to modify the association between SSB intake and obesity risk in 3 prospective cohorts from the United States. We aimed to replicate these findings in 2 large Swedish cohorts. Data were available for 21,824 healthy participants from the Malmö Diet and Cancer study and 4902 healthy participants from the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk Study. Self-reported SSB intake was categorized into 4 levels (seldom, low, medium, and high). Unweighted and weighted genetic risk scores (GRSs) were constructed based on 30 body mass index [(BMI) in kg/m(2)]-associated loci, and effect modification was assessed in linear regression equations by modeling the product and marginal effects of the GRS and SSB intake adjusted for age-, sex-, and cohort-specific covariates, with BMI as the outcome. In a secondary analysis, models were additionally adjusted for putative confounders (total energy intake, alcohol consumption, smoking status, and physical activity). In an inverse variance-weighted fixed-effects meta-analysis, each SSB intake category increment was associated with a 0.18 higher BMI (SE = 0.02; P = 1.7 × 10(-20); n = 26,726). In the fully adjusted model, a nominal significant interaction between SSB intake category and the unweighted GRS was observed (P-interaction = 0.03). Comparing the participants within the top and bottom quartiles of the GRS to each increment in SSB intake was associated with 0.24 (SE = 0.04; P = 2.9 × 10(-8); n = 6766) and 0.15 (SE = 0.04; P = 1.3 × 10(-4); n = 6835) higher BMIs, respectively. The interaction observed in the Swedish cohorts is similar in magnitude to the previous analysis in US cohorts and indicates that the relation of SSB intake and BMI is stronger in people genetically predisposed to obesity.

Detailed genetic characteristics of an international large cohort of patients with Stargardt disease: ProgStar study report 8.

PubMed

Fujinami, Kaoru; Strauss, Rupert W; Chiang, John Pei-Wen; Audo, Isabelle S; Bernstein, Paul S; Birch, David G; Bomotti, Samantha M; Cideciyan, Artur V; Ervin, Ann-Margret; Marino, Meghan J; Sahel, José-Alain; Mohand-Said, Saddek; Sunness, Janet S; Traboulsi, Elias I; West, Sheila; Wojciechowski, Robert; Zrenner, Eberhart; Michaelides, Michel; Scholl, Hendrik P N

2018-06-20

To describe the genetic characteristics of the cohort enrolled in the international multicentre progression of Stargardt disease 1 (STGD1) studies (ProgStar) and to determine geographic differences based on the allele frequency. 345 participants with a clinical diagnosis of STGD1 and harbouring at least one disease-causing ABCA4 variant were enrolled from 9 centres in the USA and Europe. All variants were reviewed and in silico analysis was performed including allele frequency in public databases and pathogenicity predictions. Participants with multiple likely pathogenic variants were classified into four national subgroups (USA, UK, France, Germany), with subsequent comparison analysis of the allele frequency for each prevalent allele. 211 likely pathogenic variants were identified in the total cohort, including missense (63%), splice site alteration (18%), stop (9%) and others. 50 variants were novel. Exclusively missense variants were detected in 139 (50%) of 279 patients with multiple pathogenic variants. The three most prevalent variants of these patients with multiple pathogenic variants were p.G1961E (15%), p.G863A (7%) and c.5461-10 T>C (5%). Subgroup analysis revealed a statistically significant difference between the four recruiting nations in the allele frequency of nine variants. There is a large spectrum of ABCA4 sequence variants, including 50 novel variants, in a well-characterised cohort thereby further adding to the unique allelic heterogeneity in STGD1. Approximately half of the cohort harbours missense variants only, indicating a relatively mild phenotype of the ProgStar cohort. There are significant differences in allele frequencies between nations, although the three most prevalent variants are shared as frequent variants. © 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.

Prevalence of suicide attempts and their risk factors in school-aged patients with epilepsy: a population-based study.

PubMed

Harnod, Tomor; Lin, Cheng-Li; Kao, Chia-Hung

2018-02-02

Suicide prevention is a critical issue for young people. However, no large body of representative data on the risk of suicide attempts in school-aged patients with epilepsy in Taiwan or other developing countries is available. Patients aged ≤ 18 years who received a diagnosis of epilepsy between 2000 and 2012 were included in the epilepsy cohort (N = 9801). The comparison cohort was matched to the epilepsy cohort at a ratio of 4:1. We calculated the adjusted hazard ratio and 95% confidence intervals (CIs) for suicide attempts after adjustment for age, sex, urbanization level, parental occupation category, comorbidities, and follow-up time. Further analysis was performed to assess the dose-response effect on the risk of attempting suicide based on the average frequency of medical visits for epilepsy. The overall incidence rates of suicide attempts in the epilepsy and comparison cohorts were 15.7 and 5.89 per 100,000 people per year, respectively. The epilepsy cohort had a 2.34-fold higher risk of suicide being attempted (95% CI 2.17-2.52) than did the comparison cohort. Male sex, over 12 years of age, and parental occupation of office work were found to be the major risk factors for suicide attempts. Epilepsy might be an independent factor predisposing school-aged patients to suicide attempts. The results of this study could provide clinicians and governments with vital information on suicide prevention for young people with epilepsy in Taiwan and other developing countries.

Bladder cancer biomarker discovery using global metabolomic profiling of urine.

PubMed

Wittmann, Bryan M; Stirdivant, Steven M; Mitchell, Matthew W; Wulff, Jacob E; McDunn, Jonathan E; Li, Zhen; Dennis-Barrie, Aphrihl; Neri, Bruce P; Milburn, Michael V; Lotan, Yair; Wolfert, Robert L

2014-01-01

Bladder cancer (BCa) is a common malignancy worldwide and has a high probability of recurrence after initial diagnosis and treatment. As a result, recurrent surveillance, primarily involving repeated cystoscopies, is a critical component of post diagnosis patient management. Since cystoscopy is invasive, expensive and a possible deterrent to patient compliance with regular follow-up screening, new non-invasive technologies to aid in the detection of recurrent and/or primary bladder cancer are strongly needed. In this study, mass spectrometry based metabolomics was employed to identify biochemical signatures in human urine that differentiate bladder cancer from non-cancer controls. Over 1000 distinct compounds were measured including 587 named compounds of known chemical identity. Initial biomarker identification was conducted using a 332 subject sample set of retrospective urine samples (cohort 1), which included 66 BCa positive samples. A set of 25 candidate biomarkers was selected based on statistical significance, fold difference and metabolic pathway coverage. The 25 candidate biomarkers were tested against an independent urine sample set (cohort 2) using random forest analysis, with palmitoyl sphingomyelin, lactate, adenosine and succinate providing the strongest predictive power for differentiating cohort 2 cancer from non-cancer urines. Cohort 2 metabolite profiling revealed additional metabolites, including arachidonate, that were higher in cohort 2 cancer vs. non-cancer controls, but were below quantitation limits in the cohort 1 profiling. Metabolites related to lipid metabolism may be especially interesting biomarkers. The results suggest that urine metabolites may provide a much needed non-invasive adjunct diagnostic to cystoscopy for detection of bladder cancer and recurrent disease management.

Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank.

PubMed

Howard, David M; Adams, Mark J; Clarke, Toni-Kim; Wigmore, Eleanor M; Zeng, Yanni; Hagenaars, Saskia P; Lyall, Donald M; Thomson, Pippa A; Evans, Kathryn L; Porteous, David J; Nagy, Reka; Hayward, Caroline; Haley, Chris S; Smith, Blair H; Murray, Alison D; Batty, G David; Deary, Ian J; McIntosh, Andrew M

2017-01-01

Cognitive ability is a heritable trait with a polygenic architecture, for which several associated variants have been identified using genotype-based and candidate gene approaches. Haplotype-based analyses are a complementary technique that take phased genotype data into account, and potentially provide greater statistical power to detect lower frequency variants. In the present analysis, three cohort studies (n total = 48,002) were utilised: Generation Scotland: Scottish Family Health Study (GS:SFHS), the English Longitudinal Study of Ageing (ELSA), and the UK Biobank. A genome-wide haplotype-based meta-analysis of cognitive ability was performed, as well as a targeted meta-analysis of several gene coding regions. None of the assessed haplotypes provided evidence of a statistically significant association with cognitive ability in either the individual cohorts or the meta-analysis. Within the meta-analysis, the haplotype with the lowest observed P -value overlapped with the D-amino acid oxidase activator ( DAOA ) gene coding region. This coding region has previously been associated with bipolar disorder, schizophrenia and Alzheimer's disease, which have all been shown to impact upon cognitive ability. Another potentially interesting region highlighted within the current genome-wide association analysis (GS:SFHS: P = 4.09 x 10 -7 ), was the butyrylcholinesterase ( BCHE ) gene coding region. The protein encoded by BCHE has been shown to influence the progression of Alzheimer's disease and its role in cognitive ability merits further investigation. Although no evidence was found for any haplotypes with a statistically significant association with cognitive ability, our results did provide further evidence that the genetic variants contributing to the variance of cognitive ability are likely to be of small effect.

Patients with metastatic breast cancer leading to CD4+ T cell lymphopaenia have poor outcome.

PubMed

Trédan, Olivier; Manuel, Manuarii; Clapisson, Gilles; Bachelot, Thomas; Chabaud, Sylvie; Bardin-dit-Courageot, Christine; Rigal, Chantal; Biota, Cathy; Bajard, Agathe; Pasqual, Nicolas; Blay, Jean-Yves; Caux, Christophe; Ménétrier-Caux, Christine

2013-05-01

Low lymphocyte count is a prognostic factor in cancer patients including metastatic breast cancer patients (MBC) but the relative role of each lymphocyte subtype is unclear in MBC. The impact of lymphocyte subsets was analysed in two prospective MBC patients' cohorts. Cohort A patients (n=103) were included before the first line of chemotherapy and cohort B patients (n=101) were included after at least one line of chemotherapy. Extensive phenotypic analyses were performed on fresh whole blood. Plasma cytokines levels were measured using commercially available Luminex-based multiplex kits. Prognostic value of lymphocyte subsets and circulating cytokines was analysed. In both cohorts, severe lymphopaenia (<0.7 Giga/L) correlated with poor overall survival (OS) (median OS: 6.6 months versus 21.7 months in cohort A and 4.5 versus 9 months in cohort B). CD8(+), CD19(+) and CD56(+) T cell counts had no significant prognostic value for OS. After stratification (≤0.2, [0.20-0.45], >0.45 Giga/L), CD4 lymphopaenia appeared to be correlated with poor OS in both cohorts. Furthermore, severe CD4(+) lymphopaenia (≤0.2 Giga/L) was strongly correlated with poor OS in both cohorts (1.2 months versus 24.9 months in cohort A and 5.7 versus 13.1 months in cohort B). In multivariate analysis, after stratification CD4(+) lymphopaenia appeared to be an independent prognostic factor for OS in both cohorts. CD4(+) lymphopaenia correlated with low plasmatic levels of CCL22 that might directly contribute to CD4(+) lymphopaenia. CD4(+) lymphopaenia was associated with reduced OS in MBC patients regardless of the chemotherapy line. Decreased levels of plasmatic CCL22 may contribute to CD4(+) lymphopaenia. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparative cost-effectiveness of metformin-based dual therapies associated with risk of cardiovascular diseases among Chinese patients with type 2 diabetes: Evidence from a population-based national cohort in Taiwan.

PubMed

Ou, Huang-Tz; Chen, Yen-Ting; Liu, Ya-Ming; Wu, Jin-Shang

2016-06-01

To assess the cost-effectiveness of metformin-based dual therapies associated with cardiovascular disease (CVD) risk in a Chinese population with type 2 diabetes. We utilized Taiwan's National Health Insurance Research Database (NHIRD) 1997-2011, which is derived from the claims of National Health Insurance, a mandatory-enrollment single-payer system that covers over 99% of Taiwan's population. Four metformin-based dual therapy cohorts were used, namely a reference group of metformin plus sulfonylureas (Metformin-SU) and metformin plus acarbose, metformin plus thiazolidinediones (Metformin-TZD), and metformin plus glinides (Metformin-glinides). Using propensity scores, each subject in a comparison cohort was 1:1 matched to a referent. The effectiveness outcome was CVD risk. Only direct medical costs were included. The Markov chain model was applied to project lifetime outcomes, discounted at 3% per annum. The bootstrapping technique was performed to assess uncertainty in analysis. Metformin-glinides was most cost-effective in the base-case analysis; Metformin-glinides saved $194 USD for one percentage point of reduction in CVD risk, as compared to Metformin-SU. However, for the elderly or those with severe diabetic complications, Metformin-TZD, especially pioglitazone, was more suitable; as compared to Metformin-SU, Metformin-TZD saved $840.1 USD per percentage point of reduction in CVD risk. Among TZDs, Metformin-pioglitazone saved $1831.5 USD per percentage point of associated CVD risk reduction, as compared to Metformin-rosiglitazone. When CVD is considered an important clinical outcome, Metformin-pioglitazone is cost-effective, in particular for the elderly and those with severe diabetic complications. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Population-based cohort study on comparative effectiveness and safety of biologics in inflammatory bowel disease

PubMed Central

Trotta, Francesco; Cascini, Silvia; Agabiti, Nera; Kohn, Anna; Gasbarrini, Antonio; Davoli, Marina; Addis, Antonio

2018-01-01

Background The comparison of effectiveness and safety of anti-tumor necrosis factor-alpha agents for the treatment of inflammatory bowel disease (IBD) is relevant for clinical practice and stakeholders. Objective The objective of this study was to compare the risk of abdominal surgery, steroid utilization, and hospitalization for infection in Crohn’s disease (CD) or ulcerative colitis (UC) patients newly treated with infliximab (IFX) or adalimumab (ADA). Methods A retrospective population-based cohort study was performed using health information systems data from Lazio region, Italy. Patients with CD or UC diagnosis were enrolled at first prescription of IFX or ADA during 2008–2014 (index date). Only new drug users were followed for 2 years from the index date. IFX versus ADA adjusted hazard ratios were calculated applying “intention-to-treat” approach, controlling for several characteristics and stratifying the analysis on steroid use according to previous drug utilization. Sensitivity analyses were performed according to “as-treated” approach, adjusting for propensity score, censoring at switching or discontinuation, and evaluating different lengths of follow-up periods. Results We enrolled 1,432 IBD patients (42% and 83% exposed to IFX for CD and UC, respectively). In both diseases, treatment effects did not differ in any outcome considered, and sensitivity analyses confirmed the results from the main analysis. Conclusion In our population-based cohort study, effectiveness and safety data in new users of ADA or IFX with CD or UC were comparable for the outcomes we tested. PMID:29440933

Disrupted modular organization of resting-state cortical functional connectivity in U.S. military personnel following concussive ‘mild’ blast-related traumatic brain injury†

PubMed Central

Han, Kihwan; Mac Donald, Christine L.; Johnson, Ann M.; Barnes, Yolanda; Wierzechowski, Linda; Zonies, David; Oh, John; Flaherty, Stephen; Fang, Raymond; Raichle, Marcus E.; Brody, David L.

2013-01-01

Blast-related traumatic brain injury (TBI) has been one of the “signature injuries” of the wars in Iraq and Afghanistan. However, neuroimaging studies in concussive ‘mild’ blast-related TBI have been challenging due to the absence of abnormalities in computed tomography or conventional magnetic resonance imaging (MRI) and the heterogeneity of the blast-related injury mechanisms. The goal of this study was to address these challenges utilizing single-subject, module-based graph theoretic analysis of resting-state functional MRI (fMRI) data. We acquired 20 minutes of resting-state fMRI in 63 U.S. military personnel clinically diagnosed with concussive blast-related TBI and 21 U.S. military controls who had blast exposures but no diagnosis of TBI. All subjects underwent an initial scan within 90 days post-injury and 65 subjects underwent a follow-up scan 6 to 12 months later. A second independent cohort of 40 U.S. military personnel with concussive blast-related TBI patients served as a validation dataset. The second independent cohort underwent an initial scan within 30 days post-injury. 75% of scans were of good quality, with exclusions primarily due to excessive subject motion. Network analysis of the subset of these subjects in the first cohort with good quality scans revealed spatially localized reductions in participation coefficient, a measure of between-module connectivity, in the TBI patients relative to the controls at the time of the initial scan. These group differences were less prominent on the follow-up scans. The 15 brain areas with the most prominent reductions in participation coefficient were next used as regions of interest (ROIs) for single-subject analyses. In the first TBI cohort, more subjects than would be expected by chance (27/47 versus 2/47 expected, p < 0.0001) had 3 or more brain regions with abnormally low between-module connectivity relative to the controls on the initial scans. On the follow-up scans, more subjects than expected by chance (5/37, p = 0.044) but fewer subjects than on the initial scans had 3 or more brain regions with abnormally low between-module connectivity. Analysis of the second TBI cohort validation dataset with no free parameters provided a partial replication; again more subjects than expected by chance (8/31, p = 0.006) had 3 or more brain regions with abnormally low between-module connectivity on the initial scans, but the numbers were not significant (2/27, p = 0.276) on the follow-up scans. A single-subject, multivariate analysis by probabilistic principal component analysis of the between-module connectivity in the 15 identified ROIs, showed that 31/47 subjects in the first TBI cohort were found to be abnormal relative to the controls on the initial scans. In the second TBI cohort, 9/31 patients were found to be abnormal in identical multivariate analysis with no free parameters. Again, there were not substantial differences on the follow-up scans. Taken together, these results indicate that single-subject, module-based graph theoretic analysis of resting-state fMRI provides potentially useful information for concussive blast-related TBI if high quality scans can be obtained. The underlying biological mechanisms and consequences of disrupted between-module connectivity are unknown, thus further studies are required. PMID:23968735

Why is the death rate from lung cancer falling in the Russian Federation?

PubMed

Shkolnikov, V; McKee, M; Leon, D; Chenet, L

1999-03-01

Age standardised death rates (European standard population) from lung cancer in the Russian Federation, have been rising since at least 1965, levelled out in the late 1980s and have subsequently decreased. The reasons for this decline are not apparent. This study seeks to identify the reasons for the decline in mortality from lung cancer in the Russian Federation in the 1990s. Changes in age-specific mortality from lung cancer in the Russian Federation between 1990 are described and age-cohort analysis, based on age-specific death rates for lung cancer is undertaken for the period 1965 to 1995. As other work has shown that any recent deterioration in coding of cause of death has been confined largely to the elderly, this suggests that the trend is not a coding artefact. Age-period-cohort analysis demonstrates the existence of a marked birth cohort effect, with two major peaks corresponding to those born around 1926 and 1938. These groups would have reached their early teens during the second world war and the period immediately after the death of Stalin, respectively. The present downward trend in death rates from lung cancer in the Russian Federation is partly due to a cohort effect and it is expected that this will soon reverse, with a second peak occurring in about 2003.

Long-term health experience of jet engine manufacturing workers: V. Issues with the analysis of non-malignant central nervous system neoplasms.

PubMed

Buchanich, Jeanine M; Youk, Ada O; Marsh, Gary M; Kennedy, Kathleen J; Lacey, Steven E; Hancock, Roger P; Esmen, Nurtan A; Cunningham, Michael A; Leiberman, Frank S; Fleissner, Mary Lou

2011-01-01

We attempted to examine non-malignant central nervous system (CNS) neoplasms incidence rates for workers at 8 jet engine manufacturing facilities in Connecticut. The objective of this manuscript is to describe difficulties encountered regarding these analyses to aid future studies. We traced the cohort for incident cases of CNS neoplasms in states where 95% of deaths in the total cohort occurred. We used external and internal analyses in an attempt to obtain the true risk of non-malignant CNS in the cohort. Because these analyses were limited by data constraints, we conducted sensitivity analyses, including using state driver's license data to adjust person-year stop dates to help minimize underascertainment and more accurately determine cohort risk estimates. We identified 3 unanticipated challenges: case identification, determination of population-based cancer incidence rates, and handling of case underascertainment. These factors precluded an accurate assessment of non-malignant CNS neoplasm incidence risks in this occupational epidemiology study. The relatively recent (2004) mandate of capturing non-malignant CNS tumor data at the state level means that, in time, it may be possible to conduct external analyses of these data. Meanwhile, similar occupational epidemiology studies may be limited to descriptive analysis of the non-malignant CNS case characteristics.

Whole transcriptome RNA-Seq analysis of breast cancer recurrence risk using formalin-fixed paraffin-embedded tumor tissue.

PubMed

Sinicropi, Dominick; Qu, Kunbin; Collin, Francois; Crager, Michael; Liu, Mei-Lan; Pelham, Robert J; Pho, Mylan; Dei Rossi, Andrew; Jeong, Jennie; Scott, Aaron; Ambannavar, Ranjana; Zheng, Christina; Mena, Raul; Esteban, Jose; Stephans, James; Morlan, John; Baker, Joffre

2012-01-01

RNA biomarkers discovered by RT-PCR-based gene expression profiling of archival formalin-fixed paraffin-embedded (FFPE) tissue form the basis for widely used clinical diagnostic tests; however, RT-PCR is practically constrained in the number of transcripts that can be interrogated. We have developed and optimized RNA-Seq library chemistry as well as bioinformatics and biostatistical methods for whole transcriptome profiling from FFPE tissue. The chemistry accommodates low RNA inputs and sample multiplexing. These methods both enable rediscovery of RNA biomarkers for disease recurrence risk that were previously identified by RT-PCR analysis of a cohort of 136 patients, and also identify a high percentage of recurrence risk markers that were previously discovered using DNA microarrays in a separate cohort of patients, evidence that this RNA-Seq technology has sufficient precision and sensitivity for biomarker discovery. More than two thousand RNAs are strongly associated with breast cancer recurrence risk in the 136 patient cohort (FDR <10%). Many of these are intronic RNAs for which corresponding exons are not also associated with disease recurrence. A number of the RNAs associated with recurrence risk belong to novel RNA networks. It will be important to test the validity of these novel associations in whole transcriptome RNA-Seq screens of other breast cancer cohorts.

Whole Transcriptome RNA-Seq Analysis of Breast Cancer Recurrence Risk Using Formalin-Fixed Paraffin-Embedded Tumor Tissue

PubMed Central

Sinicropi, Dominick; Qu, Kunbin; Collin, Francois; Crager, Michael; Liu, Mei-Lan; Pelham, Robert J.; Pho, Mylan; Rossi, Andrew Dei; Jeong, Jennie; Scott, Aaron; Ambannavar, Ranjana; Zheng, Christina; Mena, Raul; Esteban, Jose; Stephans, James; Morlan, John; Baker, Joffre

2012-01-01

RNA biomarkers discovered by RT-PCR-based gene expression profiling of archival formalin-fixed paraffin-embedded (FFPE) tissue form the basis for widely used clinical diagnostic tests; however, RT-PCR is practically constrained in the number of transcripts that can be interrogated. We have developed and optimized RNA-Seq library chemistry as well as bioinformatics and biostatistical methods for whole transcriptome profiling from FFPE tissue. The chemistry accommodates low RNA inputs and sample multiplexing. These methods both enable rediscovery of RNA biomarkers for disease recurrence risk that were previously identified by RT-PCR analysis of a cohort of 136 patients, and also identify a high percentage of recurrence risk markers that were previously discovered using DNA microarrays in a separate cohort of patients, evidence that this RNA-Seq technology has sufficient precision and sensitivity for biomarker discovery. More than two thousand RNAs are strongly associated with breast cancer recurrence risk in the 136 patient cohort (FDR <10%). Many of these are intronic RNAs for which corresponding exons are not also associated with disease recurrence. A number of the RNAs associated with recurrence risk belong to novel RNA networks. It will be important to test the validity of these novel associations in whole transcriptome RNA-Seq screens of other breast cancer cohorts. PMID:22808097

Maternal cell phone use during pregnancy and child behavioral problems in five birth cohorts.

PubMed

Birks, Laura; Guxens, Mònica; Papadopoulou, Eleni; Alexander, Jan; Ballester, Ferran; Estarlich, Marisa; Gallastegi, Mara; Ha, Mina; Haugen, Margaretha; Huss, Anke; Kheifets, Leeka; Lim, Hyungryul; Olsen, Jørn; Santa-Marina, Loreto; Sudan, Madhuri; Vermeulen, Roel; Vrijkotte, Tanja; Cardis, Elisabeth; Vrijheid, Martine

2017-07-01

Previous studies have reported associations between prenatal cell phone use and child behavioral problems, but findings have been inconsistent and based on retrospective assessment of cell phone use. This study aimed to assess this association in a multi-national analysis, using data from three cohorts with prospective data on prenatal cell phone use, together with previously published data from two cohorts with retrospectively collected cell phone use data. We used individual participant data from 83,884 mother-child pairs in the five cohorts from Denmark (1996-2002), Korea (2006-2011), the Netherlands (2003-2004), Norway (2004-2008), and Spain (2003-2008). We categorized cell phone use into none, low, medium, and high, based on frequency of calls during pregnancy reported by the mothers. Child behavioral problems (reported by mothers using the Strengths and Difficulties Questionnaire or Child Behavior Checklist) were classified in the borderline/clinical and clinical ranges using validated cut-offs in children aged 5-7years. Cohort specific risk estimates were meta-analyzed. Overall, 38.8% of mothers, mostly from the Danish cohort, reported no cell phone use during pregnancy and these mothers were less likely to have a child with overall behavioral, hyperactivity/inattention or emotional problems. Evidence for a trend of increasing risk of child behavioral problems through the maternal cell phone use categories was observed for hyperactivity/inattention problems (OR for problems in the clinical range: 1.11, 95%CI 1.01, 1.22; 1.28, 95%CI 1.12, 1.48, among children of medium and high users, respectively). This association was fairly consistent across cohorts and between cohorts with retrospectively and prospectively collected cell phone use data. Maternal cell phone use during pregnancy may be associated with an increased risk for behavioral problems, particularly hyperactivity/inattention problems, in the offspring. The interpretation of these results is unclear as uncontrolled confounding may influence both maternal cell phone use and child behavioral problems. Copyright © 2017 Elsevier Ltd. All rights reserved.

CONSUMPTION OF ANIMAL FOODS AND ENDOMETRIAL CANCER RISK: A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS

PubMed Central

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

2008-01-01

This paper summarizes and quantifies the current evidence relating dietary intake of animal products and endometrial cancer. Literature searches were conducted to identify peer-reviewed manuscripts published up to December 2006. Twenty-two manuscripts from three cohort studies and 16 case-control studies were identified. One of these cohort studies evaluated only fried meat and another only milk consumption; they were not included in our meta-analyses. The third cohort study identified did not present exposure levels and could not be included in dose-response meta-analysis. This cohort study did not show an association with meat or red meat consumption. Random-effects dose-response summary estimates for case-control studies evaluating these foods were 1.26 (95% CI: 1.03–1.54) per 100 g/day of total meat, 1.51 (95% CI: 1.19–1.93) per 100 g/day of red meat, 1.03 (95% CI: 0.32–3.28) per 100 g/day of poultry, 1.04 (95% CI: 0.55–1.98) per 100 g/day of fish, and 0.97 (95% CI: 0.93–1.01) per serving of dairy. Our meta-analysis, based on case-control data, suggests that meat consumption, particularly red meat, increases endometrial cancer risk. The current literature does not support an association with dairy products, while the evidence is inconsistent for poultry, fish, and eggs. More studies, particularly prospective studies, are needed. PMID:17638104

MORTALITY AMONG PARTICIPANTS IN THE AGRICULTURAL HEALTH STUDY

EPA Science Inventory

Purpose: This analysis of the Agricultural Health Study cohort assesses the mortality experience of licensed pesticide applicators and their spouses.

Methods: This report is based on 52,393 private applicators (who are mostly farmers) and 32,345 spouses of farmers in Iowa...

Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts.

PubMed

Jelenkovic, Aline; Sund, Reijo; Hur, Yoon-Mi; Yokoyama, Yoshie; Hjelmborg, Jacob V B; Möller, Sören; Honda, Chika; Magnusson, Patrik K E; Pedersen, Nancy L; Ooki, Syuichi; Aaltonen, Sari; Stazi, Maria A; Fagnani, Corrado; D'Ippolito, Cristina; Freitas, Duarte L; Maia, José Antonio; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rebato, Esther; Busjahn, Andreas; Kandler, Christian; Saudino, Kimberly J; Jang, Kerry L; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Gao, Wenjing; Yu, Canqing; Li, Liming; Corley, Robin P; Huibregtse, Brooke M; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth J F; Heikkilä, Kauko; Wardle, Jane; Llewellyn, Clare H; Fisher, Abigail; McAdams, Tom A; Eley, Thalia C; Gregory, Alice M; He, Mingguang; Ding, Xiaohu; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Tarnoki, Adam D; Tarnoki, David L; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Burt, S Alexandra; Klump, Kelly L; Silberg, Judy L; Eaves, Lindon J; Maes, Hermine H; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Gatz, Margaret; Butler, David A; Bartels, Meike; van Beijsterveldt, Toos C E M; Craig, Jeffrey M; Saffery, Richard; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Martin, Nicholas G; Medland, Sarah E; Montgomery, Grant W; Swan, Gary E; Krasnow, Ruth; Tynelius, Per; Lichtenstein, Paul; Haworth, Claire M A; Plomin, Robert; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Harden, K Paige; Tucker-Drob, Elliot M; Spector, Timothy; Mangino, Massimo; Lachance, Genevieve; Baker, Laura A; Tuvblad, Catherine; Duncan, Glen E; Buchwald, Dedra; Willemsen, Gonneke; Skytthe, Axel; Kyvik, Kirsten O; Christensen, Kaare; Öncel, Sevgi Y; Aliev, Fazil; Rasmussen, Finn; Goldberg, Jack H; Sørensen, Thorkild I A; Boomsma, Dorret I; Kaprio, Jaakko; Silventoinen, Karri

2016-06-23

Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1-19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments.

Efficacy and tolerability of vildagliptin-based versus comparative dual therapy in type 2 diabetes : Results of the Austrian subpopulation of the EDGE study.

PubMed

Brath, Helmut; Bialek, Christoph; Gingl, Ewald; Resl, Michael; Prager, Rudolf; Ratzinger, Michaela

2015-04-01

The aim of this post hoc analysis of data from the Austrian subpopulation of the EDGE study was the evaluation of the effectiveness and tolerability of vildagliptin as an add-on to an existing oral antidiabetic (OAD) monotherapy versus a combination therapy with two OADs without vildagliptin in patients with inadequately controlled type 2 diabetes. In Austria, 422 patients were included. In the framework of regular visits (at baseline, about once per quarter, and at the study end, after 12 months), adverse events (AEs), courses, and changes of therapy were recorded. In addition to the primary end point defined in the primary study, i.e., a reduction of HbA1c by > 0.3 % without hypoglycemia, weight gain ≥ 5 %, peripheral edema, or discontinuation due to gastrointestinal events, the most clinically relevant secondary end point, i.e., HbA1c reduction < 7 % without hypoglycemia or ≥ 3 % increase in body weight after 12 months was used for the analysis of the Austrian data. The initial HbA1c of all enrolled patients was 8.3 ± 1.4 %. The mean reduction of HbA1c was - 1.1 % in the vildagliptin cohort and - 1.0 % in the comparator cohort. In the vildagliptin cohort, 56.4 % of patients, and in the comparator cohort, 45.9 % of patients, reached the primary end point (odds ratio: 1.53, p = 0.04). In the vildagliptin cohort, 18.7 % of patients, and in the comparator cohort, 16.9 % of patients, reached the secondary end point (odds ratio: 1.13, p = 0.68). The incidence of hypoglycemic events (two in each cohort), AEs (approximately 15 % in each cohort), and serious AEs (approximately 2 % in each cohort) was comparable between the two groups. In a "real-life" setting, the effectiveness of vildagliptin as second-line treatment is superior to comparator OADs with regard to a reduction in HbA1c of greater than 0.3 % from baseline without well-recognized side effects in patients with inadequately controlled type 2 diabetes (mean baseline HbA1c: 8.5 % (vildagliptin cohort) vs. 8.1 % (comparator cohort)).

Analysis of Clinical Cohort Data Using Nested Case-control and Case-cohort Sampling Designs. A Powerful and Economical Tool.

PubMed

Ohneberg, K; Wolkewitz, M; Beyersmann, J; Palomar-Martinez, M; Olaechea-Astigarraga, P; Alvarez-Lerma, F; Schumacher, M

2015-01-01

Sampling from a large cohort in order to derive a subsample that would be sufficient for statistical analysis is a frequently used method for handling large data sets in epidemiological studies with limited resources for exposure measurement. For clinical studies however, when interest is in the influence of a potential risk factor, cohort studies are often the first choice with all individuals entering the analysis. Our aim is to close the gap between epidemiological and clinical studies with respect to design and power considerations. Schoenfeld's formula for the number of events required for a Cox' proportional hazards model is fundamental. Our objective is to compare the power of analyzing the full cohort and the power of a nested case-control and a case-cohort design. We compare formulas for power for sampling designs and cohort studies. In our data example we simultaneously apply a nested case-control design with a varying number of controls matched to each case, a case cohort design with varying subcohort size, a random subsample and a full cohort analysis. For each design we calculate the standard error for estimated regression coefficients and the mean number of distinct persons, for whom covariate information is required. The formula for the power of a nested case-control design and the power of a case-cohort design is directly connected to the power of a cohort study using the well known Schoenfeld formula. The loss in precision of parameter estimates is relatively small compared to the saving in resources. Nested case-control and case-cohort studies, but not random subsamples yield an attractive alternative for analyzing clinical studies in the situation of a low event rate. Power calculations can be conducted straightforwardly to quantify the loss of power compared to the savings in the num-ber of patients using a sampling design instead of analyzing the full cohort.

Cost Utility Analysis of Topical Steroids Compared With Dietary Elimination for Treatment of Eosinophilic Esophagitis.

PubMed

Cotton, Cary C; Erim, Daniel; Eluri, Swathi; Palmer, Sarah H; Green, Daniel J; Wolf, W Asher; Runge, Thomas M; Wheeler, Stephanie; Shaheen, Nicholas J; Dellon, Evan S

2017-06-01

Topical corticosteroids or dietary elimination are recommended as first-line therapies for eosinophilic esophagitis, but data to directly compare these therapies are scant. We performed a cost utility comparison of topical corticosteroids and the 6-food elimination diet (SFED) in treatment of eosinophilic esophagitis, from the payer perspective. We used a modified Markov model based on current clinical guidelines, in which transition between states depended on histologic response simulated at the individual cohort-member level. Simulation parameters were defined by systematic review and meta-analysis to determine the base-case estimates and bounds of uncertainty for sensitivity analysis. Meta-regression models included adjustment for differences in study and cohort characteristics. In the base-case scenario, topical fluticasone was about as effective as SFED but more expensive at a 5-year time horizon ($9261.58 vs $5719.72 per person). SFED was more effective and less expensive than topical fluticasone and topical budesonide in the base-case scenario. Probabilistic sensitivity analysis revealed little uncertainty in relative treatment effectiveness. There was somewhat greater uncertainty in the relative cost of treatments; most simulations found SFED to be less expensive. In a cost utility analysis comparing topical corticosteroids and SFED for first-line treatment of eosinophilic esophagitis, the therapies were similar in effectiveness. SFED was on average less expensive, and more cost effective in most simulations, than topical budesonide and topical fluticasone, from a payer perspective and not accounting for patient-level costs or quality of life. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Multidisciplinary clinic approach improves overall survival outcomes of patients with metastatic germ-cell tumors.

PubMed

Albany, C; Adra, N; Snavely, A C; Cary, C; Masterson, T A; Foster, R S; Kesler, K; Ulbright, T M; Cheng, L; Chovanec, M; Taza, F; Ku, K; Brames, M J; Hanna, N H; Einhorn, L H

2018-02-01

To report our experience utilizing a multidisciplinary clinic (MDC) at Indiana University (IU) since the publication of the International Germ Cell Cancer Collaborative Group (IGCCCG), and to compare our overall survival (OS) to that of the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program. We conducted a retrospective analysis of all patients with metastatic germ-cell tumor (GCT) seen at IU from 1998 to 2014. A total of 1611 consecutive patients were identified, of whom 704 patients received an initial evaluation by our MDC (including medical oncology, pathology, urology and thoracic surgery) and started first-line chemotherapy at IU. These 704 patients were eligible for analysis. All patients in this cohort were treated with cisplatin-etoposide-based combination chemotherapy. We compared the progression-free survival (PFS) and OS of patients treated at IU with that of the published IGCCCG cohort. OS of the IU testis cancer primary cohort (n = 622) was further compared with the SEER data of 1283 patients labeled with 'distant' disease. The Kaplan-Meier method was used to estimate PFS and OS. With a median follow-up of 4.4 years, patients with good, intermediate, and poor risk disease by IGCCCG criteria treated at IU had 5-year PFS of 90%, 84%, and 54% and 5-year OS of 97%, 92%, and 73%, respectively. The 5-year PFS for all patients in the IU cohort was 79% [95% confidence interval (CI) 76% to 82%]. The 5-year OS for the IU cohort was 90% (95% CI 87% to 92%). IU testis cohort had 5-year OS 94% (95% CI 91% to 96%) versus 75% (95% CI 73% to 78%) for the SEER 'distant' cohort between 2000 and 2014, P-value <0.0001. The MDC approach to GCT at high-volume cancer center associated with improved OS outcomes in this contemporary dataset. OS is significantly higher in the IU cohort compared with the IGCCCG and SEER 'distant' cohort. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Machine Learning-Augmented Propensity Score-Adjusted Multilevel Mixed Effects Panel Analysis of Hands-On Cooking and Nutrition Education versus Traditional Curriculum for Medical Students as Preventive Cardiology: Multisite Cohort Study of 3,248 Trainees over 5 Years

PubMed Central

Dart, Lyn; Vanbeber, Anne; Smith-Barbaro, Peggy; Costilla, Vanessa; Samuel, Charlotte; Terregino, Carol A.; Abali, Emine Ercikan; Dollinger, Beth; Baumgartner, Nicole; Kramer, Nicholas; Seelochan, Alex; Taher, Sabira; Deutchman, Mark; Evans, Meredith; Ellis, Robert B.; Oyola, Sonia; Maker-Clark, Geeta; Budnick, Isadore; Tran, David; DeValle, Nicole; Shepard, Rachel; Chow, Erika; Petrin, Christine; Razavi, Alexander; McGowan, Casey; Grant, Austin; Bird, Mackenzie; Carry, Connor; McGowan, Glynis; McCullough, Colleen; Berman, Casey M.; Dotson, Kerri; Sarris, Leah; Harlan, Timothy S.; Co-investigators, on behalf of the CHOP

2018-01-01

Background Cardiovascular disease (CVD) annually claims more lives and costs more dollars than any other disease globally amid widening health disparities, despite the known significant reductions in this burden by low cost dietary changes. The world's first medical school-based teaching kitchen therefore launched CHOP-Medical Students as the largest known multisite cohort study of hands-on cooking and nutrition education versus traditional curriculum for medical students. Methods This analysis provides a novel integration of artificial intelligence-based machine learning (ML) with causal inference statistics. 43 ML automated algorithms were tested, with the top performer compared to triply robust propensity score-adjusted multilevel mixed effects regression panel analysis of longitudinal data. Inverse-variance weighted fixed effects meta-analysis pooled the individual estimates for competencies. Results 3,248 unique medical trainees met study criteria from 20 medical schools nationally from August 1, 2012, to June 26, 2017, generating 4,026 completed validated surveys. ML analysis produced similar results to the causal inference statistics based on root mean squared error and accuracy. Hands-on cooking and nutrition education compared to traditional medical school curriculum significantly improved student competencies (OR 2.14, 95% CI 2.00–2.28, p < 0.001) and MedDiet adherence (OR 1.40, 95% CI 1.07–1.84, p = 0.015), while reducing trainees' soft drink consumption (OR 0.56, 95% CI 0.37–0.85, p = 0.007). Overall improved competencies were demonstrated from the initial study site through the scale-up of the intervention to 10 sites nationally (p < 0.001). Discussion This study provides the first machine learning-augmented causal inference analysis of a multisite cohort showing hands-on cooking and nutrition education for medical trainees improves their competencies counseling patients on nutrition, while improving students' own diets. This study suggests that the public health and medical sectors can unite population health management and precision medicine for a sustainable model of next-generation health systems providing effective, equitable, accessible care beginning with reversing the CVD epidemic. PMID:29850526

Machine Learning-Augmented Propensity Score-Adjusted Multilevel Mixed Effects Panel Analysis of Hands-On Cooking and Nutrition Education versus Traditional Curriculum for Medical Students as Preventive Cardiology: Multisite Cohort Study of 3,248 Trainees over 5 Years.

PubMed

Monlezun, Dominique J; Dart, Lyn; Vanbeber, Anne; Smith-Barbaro, Peggy; Costilla, Vanessa; Samuel, Charlotte; Terregino, Carol A; Abali, Emine Ercikan; Dollinger, Beth; Baumgartner, Nicole; Kramer, Nicholas; Seelochan, Alex; Taher, Sabira; Deutchman, Mark; Evans, Meredith; Ellis, Robert B; Oyola, Sonia; Maker-Clark, Geeta; Dreibelbis, Tomi; Budnick, Isadore; Tran, David; DeValle, Nicole; Shepard, Rachel; Chow, Erika; Petrin, Christine; Razavi, Alexander; McGowan, Casey; Grant, Austin; Bird, Mackenzie; Carry, Connor; McGowan, Glynis; McCullough, Colleen; Berman, Casey M; Dotson, Kerri; Niu, Tianhua; Sarris, Leah; Harlan, Timothy S; Co-Investigators, On Behalf Of The Chop

2018-01-01

Cardiovascular disease (CVD) annually claims more lives and costs more dollars than any other disease globally amid widening health disparities, despite the known significant reductions in this burden by low cost dietary changes. The world's first medical school-based teaching kitchen therefore launched CHOP-Medical Students as the largest known multisite cohort study of hands-on cooking and nutrition education versus traditional curriculum for medical students. This analysis provides a novel integration of artificial intelligence-based machine learning (ML) with causal inference statistics. 43 ML automated algorithms were tested, with the top performer compared to triply robust propensity score-adjusted multilevel mixed effects regression panel analysis of longitudinal data. Inverse-variance weighted fixed effects meta-analysis pooled the individual estimates for competencies. 3,248 unique medical trainees met study criteria from 20 medical schools nationally from August 1, 2012, to June 26, 2017, generating 4,026 completed validated surveys. ML analysis produced similar results to the causal inference statistics based on root mean squared error and accuracy. Hands-on cooking and nutrition education compared to traditional medical school curriculum significantly improved student competencies (OR 2.14, 95% CI 2.00-2.28, p < 0.001) and MedDiet adherence (OR 1.40, 95% CI 1.07-1.84, p = 0.015), while reducing trainees' soft drink consumption (OR 0.56, 95% CI 0.37-0.85, p = 0.007). Overall improved competencies were demonstrated from the initial study site through the scale-up of the intervention to 10 sites nationally ( p < 0.001). This study provides the first machine learning-augmented causal inference analysis of a multisite cohort showing hands-on cooking and nutrition education for medical trainees improves their competencies counseling patients on nutrition, while improving students' own diets. This study suggests that the public health and medical sectors can unite population health management and precision medicine for a sustainable model of next-generation health systems providing effective, equitable, accessible care beginning with reversing the CVD epidemic.

Shared and Distinct Rupture Discriminants of Small and Large Intracranial Aneurysms.

PubMed

Varble, Nicole; Tutino, Vincent M; Yu, Jihnhee; Sonig, Ashish; Siddiqui, Adnan H; Davies, Jason M; Meng, Hui

2018-04-01

Many ruptured intracranial aneurysms (IAs) are small. Clinical presentations suggest that small and large IAs could have different phenotypes. It is unknown if small and large IAs have different characteristics that discriminate rupture. We analyzed morphological, hemodynamic, and clinical parameters of 413 retrospectively collected IAs (training cohort; 102 ruptured IAs). Hierarchal cluster analysis was performed to determine a size cutoff to dichotomize the IA population into small and large IAs. We applied multivariate logistic regression to build rupture discrimination models for small IAs, large IAs, and an aggregation of all IAs. We validated the ability of these 3 models to predict rupture status in a second, independently collected cohort of 129 IAs (testing cohort; 14 ruptured IAs). Hierarchal cluster analysis in the training cohort confirmed that small and large IAs are best separated at 5 mm based on morphological and hemodynamic features (area under the curve=0.81). For small IAs (<5 mm), the resulting rupture discrimination model included undulation index, oscillatory shear index, previous subarachnoid hemorrhage, and absence of multiple IAs (area under the curve=0.84; 95% confidence interval, 0.78-0.88), whereas for large IAs (≥5 mm), the model included undulation index, low wall shear stress, previous subarachnoid hemorrhage, and IA location (area under the curve=0.87; 95% confidence interval, 0.82-0.93). The model for the aggregated training cohort retained all the parameters in the size-dichotomized models. Results in the testing cohort showed that the size-dichotomized rupture discrimination model had higher sensitivity (64% versus 29%) and accuracy (77% versus 74%), marginally higher area under the curve (0.75; 95% confidence interval, 0.61-0.88 versus 0.67; 95% confidence interval, 0.52-0.82), and similar specificity (78% versus 80%) compared with the aggregate-based model. Small (<5 mm) and large (≥5 mm) IAs have different hemodynamic and clinical, but not morphological, rupture discriminants. Size-dichotomized rupture discrimination models performed better than the aggregate model. © 2018 American Heart Association, Inc.

The association between maternal smoking and placenta abruption: a meta-analysis.

PubMed

Shobeiri, Fatemeh; Masoumi, Seyedeh Zahra; Jenabi, Ensiyeh

2017-08-01

Several epidemiological studies have determined that maternal smoking can increase the risk of placenta abruption. To date, only a meta-analysis has been performed for assessing the relationship between smoking and placenta abruption. This meta-analysis was conducted to estimate the association between smoking and the risk of placenta abruption. A literature search was conducted in major databases such as PubMed, Web of Science, and Scopus from the earliest possible year to April 2016. The heterogeneity across studies was explored by Q-test and I 2 statistic. The publication bias was assessed using Begg's and Egger's tests. The results were reported using odds ratio (OR) estimate with its 95% confidence intervals (CI) using a random effects model. The literature search yielded 1167 publications until April 2016 with 4 309 610 participants. Based on OR estimates obtained from case-control and cohort studies, there was a significant association between smoking and placenta abruption (1.80; 95% CI: 1.75, 1.85). Based on the results of cohort studies, smoking and placenta abruption had a significant association (relative risk ratio: 1.65; 95% CI: 1.51, 1.80). Based on reports in epidemiological studies, we showed that smoking is a risk factor for placenta abruption.

Methodological improvements in voxel-based analysis of diffusion tensor images: applications to study the impact of apolipoprotein E on white matter integrity.

PubMed

Newlander, Shawn M; Chu, Alan; Sinha, Usha S; Lu, Po H; Bartzokis, George

2014-02-01

To identify regional differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) using customized preprocessing before voxel-based analysis (VBA) in 14 normal subjects with the specific genes that decrease (apolipoprotein [APO] E ε2) and that increase (APOE ε4) the risk of Alzheimer's disease. Diffusion tensor images (DTI) acquired at 1.5 Tesla were denoised with a total variation tensor regularization algorithm before affine and nonlinear registration to generate a common reference frame for the image volumes of all subjects. Anisotropic and isotropic smoothing with varying kernel sizes was applied to the aligned data before VBA to determine regional differences between cohorts segregated by allele status. VBA on the denoised tensor data identified regions of reduced FA in APOE ε4 compared with the APOE ε2 healthy older carriers. The most consistent results were obtained using the denoised tensor and anisotropic smoothing before statistical testing. In contrast, isotropic smoothing identified regional differences for small filter sizes alone, emphasizing that this method introduces bias in FA values for higher kernel sizes. Voxel-based DTI analysis can be performed on low signal to noise ratio images to detect subtle regional differences in cohorts using the proposed preprocessing techniques. Copyright © 2013 Wiley Periodicals, Inc.

National Institutes of Health Toolbox Emotion Battery for English- and Spanish-speaking adults: normative data and factor-based summary scores.

PubMed

Babakhanyan, Ida; McKenna, Benjamin S; Casaletto, Kaitlin B; Nowinski, Cindy J; Heaton, Robert K

2018-01-01

The National Institutes of Health Toolbox Emotion Battery (NIHTB-EB) is a "common currency", computerized assessment developed to measure the full spectrum of emotional health. Though comprehensive, the NIHTB-EB's 17 scales may be unwieldy for users aiming to capture more global indices of emotional functioning. NIHTB-EB was administered to 1,036 English-speaking and 408 Spanish-speaking adults as a part of the NIH Toolbox norming project. We examined the factor structure of the NIHTB-EB in English- and Spanish-speaking adults and developed factor analysis-based summary scores. Census-weighted norms were presented for English speakers, and sample-weighted norms were presented for Spanish speakers. Exploratory factor analysis for both English- and Spanish-speaking cohorts resulted in the same 3-factor solution: 1) negative affect, 2) social satisfaction, and 3) psychological well-being. Confirmatory factor analysis supported similar factor structures for English- and Spanish-speaking cohorts. Model fit indices fell within the acceptable/good range, and our final solution was optimal compared to other solutions. Summary scores based upon the normative samples appear to be psychometrically supported and should be applied to clinical samples to further validate the factor structures and investigate rates of problematic emotions in medical and psychiatric populations.

Long-Term Unemployment and Suicide: A Systematic Review and Meta-Analysis

PubMed Central

Milner, Allison; Page, Andrew; LaMontagne, Anthony D.

2013-01-01

Purpose There have been a number of reviews on the association+ between unemployment and suicide, but none have investigated how this relationship is influenced by duration of unemployment. Method A systematic review and meta-analysis was conducted of those studies that assessed duration of unemployment as a risk factor for suicide. Studies considered as eligible for inclusion were population-based cohort or case-control designs; population-based ecological designs, or hospital based clinical cohort or case-control designs published in the year 1980 or later. Results The review identified 16 eligible studies, out of a possible 10,358 articles resulting from a search of four databases: PubMed, Web of Knowledge, Scopus and Proquest. While all 16 studies measured unemployment duration in different ways, a common finding was that longer duration of unemployment was related to greater risk of suicide and suicide attempt. A random effects meta-analysis on a subsample of six cohort studies indicated that the pooled relative risk of suicide in relation to average follow-up time after unemployment was 1.70 (95% CI 1.22 to 2.18). However, results also suggested a possible habituation effect to unemployment over time, with the greatest risk of suicide occurring within five years of unemployment compared to the employed population (RR = 2.50, 95% CI 1.83 to 3.17). Relative risk appeared to decline in studies of those unemployed between 12 and 16 years compared to those currently employed (RR = 1.21, 95% CI 1.10 to 1.33). Conclusion Findings suggest that long-term unemployment is associated with greater incidence of suicide. Results of the meta-analysis suggest that risk is greatest in the first five years, and persists at a lower but elevated level up to 16 years after unemployment. These findings are limited by the paucity of data on this topic. PMID:23341881

Across-cohort QC analyses of GWAS summary statistics from complex traits.

PubMed

Chen, Guo-Bo; Lee, Sang Hong; Robinson, Matthew R; Trzaskowski, Maciej; Zhu, Zhi-Xiang; Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C; Wood, Andrew R; Locke, Adam E; Kutalik, Zoltán; Loos, Ruth J F; Frayling, Timothy M; Hirschhorn, Joel N; Yang, Jian; Wray, Naomi R; Visscher, Peter M

2016-01-01

Genome-wide association studies (GWASs) have been successful in discovering SNP trait associations for many quantitative traits and common diseases. Typically, the effect sizes of SNP alleles are very small and this requires large genome-wide association meta-analyses (GWAMAs) to maximize statistical power. A trend towards ever-larger GWAMA is likely to continue, yet dealing with summary statistics from hundreds of cohorts increases logistical and quality control problems, including unknown sample overlap, and these can lead to both false positive and false negative findings. In this study, we propose four metrics and visualization tools for GWAMA, using summary statistics from cohort-level GWASs. We propose methods to examine the concordance between demographic information, and summary statistics and methods to investigate sample overlap. (I) We use the population genetics F st statistic to verify the genetic origin of each cohort and their geographic location, and demonstrate using GWAMA data from the GIANT Consortium that geographic locations of cohorts can be recovered and outlier cohorts can be detected. (II) We conduct principal component analysis based on reported allele frequencies, and are able to recover the ancestral information for each cohort. (III) We propose a new statistic that uses the reported allelic effect sizes and their standard errors to identify significant sample overlap or heterogeneity between pairs of cohorts. (IV) To quantify unknown sample overlap across all pairs of cohorts, we propose a method that uses randomly generated genetic predictors that does not require the sharing of individual-level genotype data and does not breach individual privacy.

Across-cohort QC analyses of GWAS summary statistics from complex traits

PubMed Central

Chen, Guo-Bo; Lee, Sang Hong; Robinson, Matthew R; Trzaskowski, Maciej; Zhu, Zhi-Xiang; Winkler, Thomas W; Day, Felix R; Croteau-Chonka, Damien C; Wood, Andrew R; Locke, Adam E; Kutalik, Zoltán; Loos, Ruth J F; Frayling, Timothy M; Hirschhorn, Joel N; Yang, Jian; Wray, Naomi R; Visscher, Peter M

2017-01-01

Genome-wide association studies (GWASs) have been successful in discovering SNP trait associations for many quantitative traits and common diseases. Typically, the effect sizes of SNP alleles are very small and this requires large genome-wide association meta-analyses (GWAMAs) to maximize statistical power. A trend towards ever-larger GWAMA is likely to continue, yet dealing with summary statistics from hundreds of cohorts increases logistical and quality control problems, including unknown sample overlap, and these can lead to both false positive and false negative findings. In this study, we propose four metrics and visualization tools for GWAMA, using summary statistics from cohort-level GWASs. We propose methods to examine the concordance between demographic information, and summary statistics and methods to investigate sample overlap. (I) We use the population genetics Fst statistic to verify the genetic origin of each cohort and their geographic location, and demonstrate using GWAMA data from the GIANT Consortium that geographic locations of cohorts can be recovered and outlier cohorts can be detected. (II) We conduct principal component analysis based on reported allele frequencies, and are able to recover the ancestral information for each cohort. (III) We propose a new statistic that uses the reported allelic effect sizes and their standard errors to identify significant sample overlap or heterogeneity between pairs of cohorts. (IV) To quantify unknown sample overlap across all pairs of cohorts, we propose a method that uses randomly generated genetic predictors that does not require the sharing of individual-level genotype data and does not breach individual privacy. PMID:27552965

Impact of Month of Birth on the Risk of Development of Autoimmune Addison's Disease

PubMed Central

Fichna, Marta; Mitchell, Anna L.; Napier, Catherine M.; Gan, Earn; Ruchała, Marek; Santibanez-Koref, Mauro; Pearce, Simon H.

2016-01-01

Context: The pathogenesis of autoimmune Addison's disease (AAD) is thought to be due to interplay of genetic, immune, and environmental factors. A month-of-birth effect, with increased risk for those born in autumn/winter months, has been described in autoimmune conditions such as type 1 diabetes and autoimmune thyroid disease. Objective: Month-of-birth effect was investigated in 2 independent cohorts of AAD subjects. Design, Setting, and Patients: The monthly distribution of birth in AAD patients was compared with that of the general population using the cosinor test. A total of 415 AAD subjects from the United Kingdom cohort were compared with 8 180 180 United Kingdom births, and 231 AAD subjects from the Polish cohort were compared with 2 421 384 Polish births. Main Outcome Measures: Association between month of birth and the susceptibility to AAD. Results: In the entire cohort of AAD subjects, month-of-birth distribution analysis showed significant periodicity with peak of births in December and trough in May (P = .028). Analysis of the odds ratio distribution based on month of birth in 2 cohorts of patients with AAD versus the general population revealed a December peak and May trough, and January peak and July trough, in the United Kingdom and Polish cohorts, respectively. Conclusion: For the first time, we demonstrate that month of birth exerts an effect on the risk of developing AAD, with excess risk in individuals born in winter months and a protective effect when born in the summer. Exposure to seasonal viral infections in the perinatal period, coupled with vitamin D deficiency, could lead to dysregulation of innate immunity affecting the risk of developing AAD. PMID:27575942

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts.

PubMed

Baquero, Maria T; Lostritto, Karen; Gustavson, Mark D; Bassi, Kimberly A; Appia, Franck; Camp, Robert L; Molinaro, Annette M; Harris, Lyndsay N; Rimm, David L

2011-11-02

Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker. MAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy. Assessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584). Quantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy.

Examining mortality risk and rate of ageing among Polish Olympic athletes: a survival follow-up from 1924 to 2012

PubMed Central

Lin, Yuhui; Gajewski, Antoni; Poznańska, Anna

2016-01-01

Objectives Population-based studies have shown that an active lifestyle reduces mortality risk. Therefore, it has been a longstanding belief that individuals who engage in frequent exercise will experience a slower rate of ageing. It is uncertain whether this widely-accepted assumption holds for intense wear-and-tear. Here, using the 88 years survival follow-up data of Polish Olympic athletes, we report for the first time on whether frequent exercise alters the rate of ageing. Design Longitudinal survival data of male elite Polish athletes who participated in the Olympic Games from year 1924 to 2010 were used. Deaths occurring before the end of World War II were excluded for reliable estimates. Setting and participants Recruited male elite athletes N=1273 were preassigned to two categorical birth cohorts—Cohort I 1890–1919; Cohort II 1920–1959—and a parametric frailty survival analysis was conducted. An event-history analysis was also conducted to adjust for medical improvements from year 1920 onwards: Cohort II. Results Our findings suggest (1) in Cohort I, for every threefold reduction in mortality risk, the rate of ageing decelerates by 1%; (2) socioeconomic transitions and interventions contribute to a reduction in mortality risk of 29% for the general population and 50% for Olympic athletes; (3) an optimum benefit gained for reducing the rate of ageing from competitive sports (Cohort I 0.086 (95% CI 0.047 to 0.157) and Cohort II 0.085 (95% CI 0.050 to 0.144)). Conclusions This study further suggests that intensive physical training during youth should be considered as a factor to improve ageing and mortality risk parameters. PMID:27091824

Potential for adult-based epidemiological studies to characterize overall cancer risks associated with a lifetime of CT scans.

PubMed

Shuryak, Igor; Lubin, Jay H; Brenner, David J

2014-06-01

Recent epidemiological studies have suggested that radiation exposure from pediatric CT scanning is associated with small excess cancer risks. However, the majority of CT scans are performed on adults, and most radiation-induced cancers appear during middle or old age, in the same age range as background cancers. Consequently, a logical next step is to investigate the effects of CT scanning in adulthood on lifetime cancer risks by conducting adult-based, appropriately designed epidemiological studies. Here we estimate the sample size required for such studies to detect CT-associated risks. This was achieved by incorporating different age-, sex-, time- and cancer type-dependent models of radiation carcinogenesis into an in silico simulation of a population-based cohort study. This approach simulated individual histories of chest and abdominal CT exposures, deaths and cancer diagnoses. The resultant sample sizes suggest that epidemiological studies of realistically sized cohorts can detect excess lifetime cancer risks from adult CT exposures. For example, retrospective analysis of CT exposure and cancer incidence data from a population-based cohort of 0.4 to 1.3 million (depending on the carcinogenic model) CT-exposed UK adults, aged 25-65 in 1980 and followed until 2015, provides 80% power for detecting cancer risks from chest and abdominal CT scans.

Assessment of response consistency and respective participant profiles in the Internet-based NutriNet-Santé Cohort.

PubMed

Andreeva, Valentina A; Galan, Pilar; Julia, Chantal; Castetbon, Katia; Kesse-Guyot, Emmanuelle; Hercberg, Serge

2014-04-01

Whereas the feasibility and effectiveness of Internet-based epidemiologic research have been established, methodological support for the quality of such data is still accumulating. We aimed to identify sociodemographic differences among members of a French cohort according to willingness to provide part of one's 15-digit national identification number (personal Social Security number (PSSN)) and to assess response consistency based on information reported on the sociodemographic questionnaire and that reflected in the PSSN. We studied 100,118 persons enrolled in an Internet-based prospective cohort study, the NutriNet-Santé Study, between 2009 and 2013. Persons aged 18 years or more who resided in France and had Internet access were eligible for enrollment. The sociodemographic profiles of participants with discordant data were compared against those of participants with concordant data via 2-sided polytomous logistic regression. In total, 84,442 participants (84.3%) provided the first 7 digits of their PSSN, and among them 5,141 (6.1%) had discordant data. Our multivariate analysis revealed differences by sex, age, education, and employment as regards response consistency patterns. The results support the quality of sociodemographic data obtained online from a large and diverse volunteer sample. The quantitative description of participant profiles according to response consistency patterns could inform future methodological work in e-epidemiology.

Sardasht-Iran cohort study of chemical warfare victims: design and methods.

PubMed

Ghazanfari, Tooba; Faghihzadeh, Soghrat; Aragizadeh, Hassan; Soroush, Mohammad-Reza; Yaraee, Roya; Mohammad Hassan, Zuhair; Foroutan, Abbas; Vaez-Mahdavi, Mohammad-Reza; Javadi, Mohammad-Ali; Moaiedmohseni, Sakine; Azizi, Fereidoun; Panahi, Yunes; Mostafaie, Ali; Ghasemi, Hassan; Shams, Jalaleddin; Pourfarzam, Shahryar; Jalali-Nadoushan, Mohammad-Reza; Fallahi, Faramarz; Ebtekar, Massoumeh; Davoudi, Seyyed-Masoud; Ghazanfari, Zeinab; Ardestani, Sussan K; Shariat-Panahi, Shamsa; Moin, Athar; Rezaei, Abbas; Kariminia, Amina; Ajdary, Soheila; Mahmoudi, Mahmoud; Roshan, Rasoul; Ghaderi, Sulayman; Babai, Mahmoud; Naghizadeh, Mohammad-Mehdi; Ghanei, Mohammad-Mostafa

2009-01-01

Insights into long-term clinical consequences of sulfur mustard have emerged from some investigations but less is known about the basic and molecular mechanisms of these complications. Sardasht-Iran Cohort Study is a comprehensive historical cohort study on Sardasht chemical victims' population which was designed to find out the long-term complications of sulfur mustard exposure and the basic mechanisms underlying clinical manifestations. This paper describes the design and methodology of Sardasht-Iran Cohort Study. In Sardasht-Iran Cohort Study, 500 individuals including 372 subjects from Sardasht, as the exposed group, and 128 subjects from Rabat, as the unexposed age-matched control group were evaluated. The exposed group was divided into two groups based on the severity of clinical complications at the time of exposure. Different samples including blood, sputum, saliva, tear, urine, and semen were collected for immunologic, hematologic, biochemical, and other laboratory analysis. Data were gathered from medical records, clinical examinations, laboratory tests, and questionnaires for psychological and lifestyle situations. The important distinctions setting this study apart from the previous ones are discussed. The Sardasht-Iran Cohort Study provides important information on various aspects of long-term consequences of sulfur mustard exposure. This database will provide a better position to suggest guidelines for the diagnosis, treatment, and prevention of delayed complications in the patients exposed to sulfur mustard.

Are stunted young Indonesian children more likely to be overweight, thin, or have high blood pressure in adolescence?

PubMed

Rachmi, Cut Novianti; Agho, Kingsley Emwinyore; Li, Mu; Baur, Louise Alison

2017-01-01

To determine whether stunted young children are at greater risk of (1) overweight/obesity or thinness, and (2) high blood pressure (HBP) in adolescence. A secondary data analysis using the Indonesian Family Life Survey waves 1 (1993) to 4 (2007). We generated a 14-year follow-up cohort (1993-2007) and two 7-year cohorts (1993-2000 and 2000-2007) of children aged 2.0-4.9 years. Stunting (HAZ < -2), thinness (BMIZ < -2), and overweight/obesity (BMIZ > +1) were determined based upon the WHO Child Growth Standards. HBP (>90th percentile) was interpreted using the 4th Report on the Diagnosis of HBP in Children and Adolescents. 765, 1083, and 1589 children were included in the 14-year cohort, and the two 7-year cohort analyses, respectively. In the 7-year cohorts, early life stunting was inversely associated with overweight/obesity (prevalence ratio 0.32 and 0.38, respectively; P < 0.05), but no significant association was found with the 14-year cohort. There was no significant association between childhood stunting and thinness at adolescence or in the odds/likelihood of having high systolic or diastolic blood pressure. We found no association between early life stunting and overweight/obesity, thinness and HBP in adolescence.

A Novel Assay for the Identification of NOTCH1 PEST Domain Mutations in Chronic Lymphocytic Leukemia

PubMed Central

Petroni, Roberta Cardoso; Muto, Nair Hideko; Sitnik, Roberta; de Carvalho, Flavia Pereira; Bacal, Nydia Strachman; Velloso, Elvira Deolinda Rodrigues Pereira; Oliveira, Gislaine Borba; Pinho, João Renato Rebello; Torres, Davi Coe; Mansur, Marcela Braga; Hassan, Rocio; Lorand-Metze, Irene Gyongyvér Heidemarie; Chiattone, Carlos Sérgio; Hamerschlak, Nelson; Mangueira, Cristovão Luis Pitangueira

2016-01-01

Aims. To develop a fast and robust DNA-based assay to detect insertions and deletions mutations in exon 34 that encodes the PEST domain of NOTCH1 in order to evaluate patients with chronic lymphocytic leukemia (CLL). Methods. We designed a multiplexed allele-specific polymerase chain reaction (PCR) combined with a fragment analysis assay to detect specifically the mutation c.7544_7545delCT and possibly other insertions and deletions in exon 34 of NOTCH1. Results. We evaluated our assay in peripheral blood samples from two cohorts of patients with CLL. The frequency of NOTCH1 mutations was 8.4% in the first cohort of 71 unselected CLL patients. We then evaluated a second cohort of 26 CLL patients with known cytogenetic abnormalities that were enriched for patients with trisomy 12. NOTCH1 mutations were detected in 43.7% of the patients with trisomy 12. Conclusions. We have developed a fast and robust assay combining allele-specific PCR and fragment analysis able to detect NOTCH1 PEST domain insertions and deletions. PMID:28074183

A comparison of propensity score-based approaches to health service evaluation: a case study of a preoperative physician-led clinic for high-risk surgical patients.

PubMed

Pham, Clarabelle T; Gibb, Catherine L; Mittinty, Murthy N; Fitridge, Robert A; Marshall, Villis R; Karnon, Jonathan D

2016-10-01

A physician-led clinic for the preoperative optimization and management of high-risk surgical patients was implemented in a South Australian public hospital in 2008. This study aimed to estimate the costs and effects of the clinic using a mixed retrospective and prospective observational study design. Alternative propensity score estimation methods were applied to retrospective routinely collected administrative and clinical data, using weighted and matched cohorts. Supplementary survey-based prospective data were collected to inform the analysis of the retrospective data and reduce potential unmeasured confounding. Using weighted cohorts, clinic patients had a significantly longer mean length of stay and higher mean cost. With the matched cohorts, reducing the calliper width resulted in a shorter mean length of stay in the clinic group, but the costs remained significantly higher. The prospective data indicated potential unmeasured confounding in all analyses other than in the most tightly matched cohorts. The application of alternative propensity-based approaches to a large sample of retrospective data, supplemented with a smaller sample of prospective data, informed a pragmatic approach to reducing potential observed and unmeasured confounding in an evaluation of a physician-led preoperative clinic. The need to generate tightly matched cohorts to reduce the potential for unmeasured confounding indicates that significant uncertainty remains around the effects of the clinic. This study illustrates the value of mixed retrospective and prospective observational study designs but also underlines the need to prospectively plan for the evaluation of costs and effects alongside the implementation of significant service innovations. © 2016 John Wiley & Sons, Ltd.

Using individual patient anatomy to predict protocol compliance for prostate intensity-modulated radiotherapy

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

Caine, Hannah; Whalley, Deborah; Kneebone, Andrew

If a prostate intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) plan has protocol violations, it is often a challenge knowing whether this is due to unfavorable anatomy or suboptimal planning. This study aimed to create a model to predict protocol violations based on patient anatomical variables and their potential relationship to target and organ at risk (OAR) end points in the setting of definitive, dose-escalated IMRT/VMAT prostate planning. Radiotherapy plans from 200 consecutive patients treated with definitive radiation for prostate cancer using IMRT or VMAT were analyzed. The first 100 patient plans (hypothesis-generating cohort) were examined to identifymore » anatomical variables that predict for dosimetric outcome, in particular OAR end points. Variables that scored significance were further assessed for their ability to predict protocol violations using a Classification and Regression Tree (CART) analysis. These results were then validated in a second group of 100 patients (validation cohort). In the initial analysis of the hypothesis-generating cohort, percentage of rectum overlap in the planning target volume (PTV) (%OR) and percentage of bladder overlap in the PTV (%OB) were highlighted as significant predictors of rectal and bladder dosimetry. Lymph node treatment was also significant for bladder outcomes. For the validation cohort, CART analysis showed that %OR of < 6%, 6% to 9% and > 9% predicted a 13%, 63%, and 100% rate of rectal protocol violations respectively. For the bladder, %OB of < 9% vs > 9% is associated with 13% vs 88% rate of bladder constraint violations when lymph nodes were not treated. If nodal irradiation was delivered, plans with a %OB of < 9% had a 59% risk of violations. Percentage of rectum and bladder within the PTV can be used to identify individual plan potential to achieve dose-volume histogram (DVH) constraints. A model based on these factors could be used to reduce planning time, improve work flow, and strengthen plan quality and consistency.« less

Spectral analysis-based risk score enables early prediction of mortality and cerebral performance in patients undergoing therapeutic hypothermia for ventricular fibrillation and comatose status

PubMed Central

Filgueiras-Rama, David; Calvo, Conrado J.; Salvador-Montañés, Óscar; Cádenas, Rosalía; Ruiz-Cantador, Jose; Armada, Eduardo; Rey, Juan Ramón; Merino, J.L.; Peinado, Rafael; Pérez-Castellano, Nicasio; Pérez-Villacastín, Julián; Quintanilla, Jorge G.; Jiménez, Santiago; Castells, Francisco; Chorro, Francisco J.; López-Sendón, J.L.; Berenfeld, Omer; Jalife, José; López de Sá, Esteban; Millet, José

2017-01-01

Background Early prognosis in comatose survivors after cardiac arrest due to ventricular fibrillation (VF) is unreliable, especially in patients undergoing mild hypothermia. We aimed at developing a reliable risk-score to enable early prediction of cerebral performance and survival. Methods Sixty-one out of 239 consecutive patients undergoing mild hypothermia after cardiac arrest, with eventual return of spontaneous circulation (ROSC), and comatose status on admission fulfilled the inclusion criteria. Background clinical variables, VF time and frequency domain fundamental variables were considered. The primary and secondary outcomes were a favorable neurological performance (FNP) during hospitalization and survival to hospital discharge, respectively. The predictive model was developed in a retrospective cohort (n=32; September 2006–September 2011, 48.5 ± 10.5 months of follow-up) and further validated in a prospective cohort (n = 29; October 2011–July 2013, 5 ± 1.8 months of follow-up). Results FNP was present in 16 (50.0%) and 21 patients (72.4%) in the retrospective and prospective cohorts, respectively. Seventeen (53.1%) and 21 patients (72.4%), respectively, survived to hospital discharge. Both outcomes were significantly associated (p < 0.001). Retrospective multivariate analysis provided a prediction model (sensitivity= 0.94, specificity = 1) that included spectral dominant frequency, derived power density and peak ratios between high and low frequency bands, and the number of shocks delivered before ROSC. Validation on the prospective cohort showed sensitivity = 0.88 and specificity = 0.91. A model-derived risk-score properly predicted 93% of FNP. Testing the model on follow-up showed a c-statistic ≥ 0.89. Conclusions A spectral analysis-based model reliably correlates time-dependent VF spectral changes with acute cerebral injury in comatose survivors undergoing mild hypothermia after cardiac arrest. PMID:25828128

Population-Based Study of Changes in Arthritis Prevalence and Arthritis Risk Factors Over Time: Generational Differences and the Role of Obesity.

PubMed

Badley, Elizabeth M; Canizares, Mayilee; Perruccio, Anthony V

2017-12-01

To investigate cohort effects in arthritis prevalence across 4 birth cohorts: World War II (born 1935-1944), older and younger baby boomers (born 1945-1954 and 1955-1964, respectively), and Generation X (born 1965-1974), and to determine whether birth cohort effects in arthritis prevalence were associated with differences in risk factors over time or period effects. Analysis of biannually collected data from the longitudinal Canadian National Population Health Survey, 1994-2011 (n = 8,817 at baseline). Data included self-reported arthritis diagnosed by a health professional, risk factors (years of education, household income, smoking, physical activity, sedentary behavior, body mass index [BMI]), and survey year as an indicator of period. We used hierarchical age-period-cohort analyses to compare the age trajectory of arthritis by birth cohort and to examine the contribution of changes in risk factors and period to cohort differences. More recent cohorts had successively a greater prevalence of arthritis. Risk factors were significantly associated with arthritis prevalence independently of cohort differences. The effects of increasing education and income over time on potentially reducing the arthritis prevalence were almost counter-balanced by effects of increasing BMI. Significant cohort-BMI and age-BMI interactions indicated an earlier age of arthritis onset for obese individuals than those of normal weight. Projections that only take into account the changing age structure of the population may underestimate future trends. Our understanding of the impact of BMI on arthritis is likely an underestimate. Cohort differences focus attention on the need to target arthritis management education to young and middle-aged adults. © 2017, American College of Rheumatology.

Trends in stage-specific incidence of prostate cancer in Norway, 1980-2010: a population-based study.

PubMed

Møller, Mette H; Kristiansen, Ivar S; Beisland, Christian; Rørvik, Jarle; Støvring, Henrik

2016-10-01

To estimate changes in the stage distribution of prostate cancer during the time period where opportunistic prostate-specific antigen (PSA) testing was introduced. Cancer stage, age, and year of diagnosis were obtained for all men aged >50 years diagnosed with prostate cancer in Norway during the period 1980-2010. Three calendar-time periods (1980-1989, 1990-2000, and 2001-2010) and three age groups (50-65, 66-74, and ≥75 years) were defined. Birth cohorts were categorised into four intervals: ≤1915, 1916-1925, 1926-1940 and ≥1941. We used Poisson regressions to conduct both a time period and cohort-based analysis of trends in the incidence of localised, regional, and distant cancer for each combination of age groups and calendar-time periods or birth cohorts, respectively. Additionally, we explored the effect of cohorts on the stage-specific incidence graphically with a Poisson regression using 5-year age groups, and by estimating cumulative incidence rates for each birth cohort. The annual incidence of localised cancers among men aged 50-65 and 66-74 years rose from 41.4 and 255.2 per 100 000, respectively, before the introduction of PSA testing to 137.9 and 418.7 in 2001-2010 afterwards, corresponding to 3.3 [95% confidence interval (CI) 3.1-3.5] and 1.6 (95% CI 1.6-1.7) fold increases. The incidence of regional cancers increased by a factor seven among men aged <75 years. The incidence of distant cancers in men aged ≥75 years decreased by 29% (95% CI 25-33%). These findings were confirmed in the cohort-based approach. Opportunistic PSA testing substantially increased the incidence of localised and regional prostate cancers among men aged 50-74 years, which was not fully compensated by the 30% decrease in incidence of distant prostate cancers in older men. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Association of an inter-arm systolic blood pressure difference with all-cause and cardiovascular mortality: An updated meta-analysis of cohort studies.

PubMed

Cao, Kaiwu; Xu, Jingsong; Shangguan, Qing; Hu, Weitong; Li, Ping; Cheng, Xiaoshu; Su, Hai

2015-01-01

To evaluate whether an association exists between an inter-arm systolic blood pressure difference (sIAD) and all-cause and cardiovascular mortality. We searched for cohort studies that evaluated the association of a sIAD and all-cause or cardiovascular mortality in the electronic databases Medline/PubMed and Embase (August 2014). Random effects models were used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Nine cohort studies (4 prospective and 5 retrospective) enrolling 15,617 participants were included. The pooled HR of all-cause mortality for a sIAD of ≥ 10 mm Hg was 1.53 (95% CI 1.14-2.06), and that for a sIAD of ≥ 15 mm Hg was 1.46 (1.13-1.88). Pooled HRs of cardiovascular mortality were 2.21 (95% CI 1.52-3.21) for a sIAD of ≥ 10mm Hg, and 1.89 (1.32-2.69) for a sIAD of ≥ 15 mm Hg. In the patient-based cohorts including hospital- and diabetes-based cohorts, both sIADs of ≥ 10 and ≥ 15 mm Hg were associated with increased all-cause (pooled HR 1.95, 95% CI 1.01-3.78 and 1.59, 1.06-2.38, respectively) and cardiovascular mortality (pooled HR 2.98, 95% CI 1.88-4.72 and 2.10, 1.07-4.13, respectively). In the community-based cohorts, however, only a sIAD of ≥ 15 mm Hg was associated with increased cardiovascular mortality (pooled HR 1.94, 95 % CI 1.12-3.35). In the patient populations, a sIAD of ≥ 10 or of ≥ 15 mm Hg could be a useful indictor for increased all-cause and cardiovascular mortality, and a sIAD of ≥ 15 mm Hg might help to predict increased cardiovascular mortality in the community populations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dementia and Traffic Accidents: A Danish Register-Based Cohort Study.

PubMed

Petersen, Jindong Ding; Siersma, Volkert; Nielsen, Connie Thurøe; Vass, Mikkel; Waldorff, Frans Boch

2016-09-27

As a consequence of a rapid growth of an ageing population, more people with dementia are expected on the roads. Little is known about whether these people are at increased risk of road traffic-related accidents. Our study aims to investigate the risk of road traffic-related accidents for people aged 65 years or older with a diagnosis of dementia in Denmark. We will conduct a nationwide population-based cohort study consisting of Danish people aged 65 or older living in Denmark as of January 1, 2008. The cohort is followed for 7 years (2008-2014). Individual's personal data are available in Danish registers and can be linked using a unique personal identification number. A person is identified with dementia if the person meets at least one of the following criteria: (1) a diagnosis of the disease in the Danish National Patient Register or in the Danish Psychiatric Central Research Register, and/or (2) at least one dementia diagnosis-related drug prescription registration in the Danish National Prescription Registry. Police-, hospital-, and emergency room-reported road traffic-related accidents occurred within the study follow-up are defined as the study outcome. Cox proportional hazard regression models are used for the main analysis. Our study protocol has 3 phases including data collection, data analysis, and reporting. The first phase of register-based data collection of 853,228 individual's personal information was completed in August, 2016. The next phase is data analysis, which is expected to be finished before December 2016, and thereafter writing publications based on the findings. The study started in January 2016 and will end in December 2018. This study covers the entire elderly population of Denmark, and thereby will avoid selection bias due to nonparticipation and loss to follow-up. Furthermore, this ensures that the study results are reliable and generalizable. However, underreporting of traffic-related accidents may occur, which will limit estimation of absolute risks.

Dementia and Traffic Accidents: A Danish Register-Based Cohort Study

PubMed Central

Siersma, Volkert; Nielsen, Connie Thurøe; Vass, Mikkel; Waldorff, Frans Boch

2016-01-01

Background As a consequence of a rapid growth of an ageing population, more people with dementia are expected on the roads. Little is known about whether these people are at increased risk of road traffic-related accidents. Objective Our study aims to investigate the risk of road traffic-related accidents for people aged 65 years or older with a diagnosis of dementia in Denmark. Methods We will conduct a nationwide population-based cohort study consisting of Danish people aged 65 or older living in Denmark as of January 1, 2008. The cohort is followed for 7 years (2008-2014). Individual’s personal data are available in Danish registers and can be linked using a unique personal identification number. A person is identified with dementia if the person meets at least one of the following criteria: (1) a diagnosis of the disease in the Danish National Patient Register or in the Danish Psychiatric Central Research Register, and/or (2) at least one dementia diagnosis-related drug prescription registration in the Danish National Prescription Registry. Police-, hospital-, and emergency room-reported road traffic-related accidents occurred within the study follow-up are defined as the study outcome. Cox proportional hazard regression models are used for the main analysis. Results Our study protocol has 3 phases including data collection, data analysis, and reporting. The first phase of register-based data collection of 853,228 individual’s personal information was completed in August, 2016. The next phase is data analysis, which is expected to be finished before December 2016, and thereafter writing publications based on the findings. The study started in January 2016 and will end in December 2018. Discussion This study covers the entire elderly population of Denmark, and thereby will avoid selection bias due to nonparticipation and loss to follow-up. Furthermore, this ensures that the study results are reliable and generalizable. However, underreporting of traffic-related accidents may occur, which will limit estimation of absolute risks. PMID:27678553

metaCCA: summary statistics-based multivariate meta-analysis of genome-wide association studies using canonical correlation analysis.

PubMed

Cichonska, Anna; Rousu, Juho; Marttinen, Pekka; Kangas, Antti J; Soininen, Pasi; Lehtimäki, Terho; Raitakari, Olli T; Järvelin, Marjo-Riitta; Salomaa, Veikko; Ala-Korpela, Mika; Ripatti, Samuli; Pirinen, Matti

2016-07-01

A dominant approach to genetic association studies is to perform univariate tests between genotype-phenotype pairs. However, analyzing related traits together increases statistical power, and certain complex associations become detectable only when several variants are tested jointly. Currently, modest sample sizes of individual cohorts, and restricted availability of individual-level genotype-phenotype data across the cohorts limit conducting multivariate tests. We introduce metaCCA, a computational framework for summary statistics-based analysis of a single or multiple studies that allows multivariate representation of both genotype and phenotype. It extends the statistical technique of canonical correlation analysis to the setting where original individual-level records are not available, and employs a covariance shrinkage algorithm to achieve robustness.Multivariate meta-analysis of two Finnish studies of nuclear magnetic resonance metabolomics by metaCCA, using standard univariate output from the program SNPTEST, shows an excellent agreement with the pooled individual-level analysis of original data. Motivated by strong multivariate signals in the lipid genes tested, we envision that multivariate association testing using metaCCA has a great potential to provide novel insights from already published summary statistics from high-throughput phenotyping technologies. Code is available at https://github.com/aalto-ics-kepaco anna.cichonska@helsinki.fi or matti.pirinen@helsinki.fi Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

metaCCA: summary statistics-based multivariate meta-analysis of genome-wide association studies using canonical correlation analysis

PubMed Central

Cichonska, Anna; Rousu, Juho; Marttinen, Pekka; Kangas, Antti J.; Soininen, Pasi; Lehtimäki, Terho; Raitakari, Olli T.; Järvelin, Marjo-Riitta; Salomaa, Veikko; Ala-Korpela, Mika; Ripatti, Samuli; Pirinen, Matti

2016-01-01

Motivation: A dominant approach to genetic association studies is to perform univariate tests between genotype-phenotype pairs. However, analyzing related traits together increases statistical power, and certain complex associations become detectable only when several variants are tested jointly. Currently, modest sample sizes of individual cohorts, and restricted availability of individual-level genotype-phenotype data across the cohorts limit conducting multivariate tests. Results: We introduce metaCCA, a computational framework for summary statistics-based analysis of a single or multiple studies that allows multivariate representation of both genotype and phenotype. It extends the statistical technique of canonical correlation analysis to the setting where original individual-level records are not available, and employs a covariance shrinkage algorithm to achieve robustness. Multivariate meta-analysis of two Finnish studies of nuclear magnetic resonance metabolomics by metaCCA, using standard univariate output from the program SNPTEST, shows an excellent agreement with the pooled individual-level analysis of original data. Motivated by strong multivariate signals in the lipid genes tested, we envision that multivariate association testing using metaCCA has a great potential to provide novel insights from already published summary statistics from high-throughput phenotyping technologies. Availability and implementation: Code is available at https://github.com/aalto-ics-kepaco Contacts: anna.cichonska@helsinki.fi or matti.pirinen@helsinki.fi Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27153689

A sensitive NanoString-based assay to score STK11 (LKB1) pathway disruption in lung adenocarcinoma

PubMed Central

Chen, Lu; Engel, Brienne E.; Welsh, Eric A.; Yoder, Sean J.; Brantley, Stephen G.; Chen, Dung-Tsa; Beg, Amer A.; Cao, Chunxia; Kaye, Frederic J.; Haura, Eric B.; Schabath, Matthew B.; Cress, W. Douglas

2016-01-01

Introduction Serine/threonine kinase 11 (STK11), better known as LKB1, is a tumor-suppressor commonly mutated in lung adenocarcinoma (LUAD). Previous work has shown that mutational inactivation of the STK11 pathway may serve as a predictive biomarker for cancer treatments including phenformin and COX-2 inhibition. Although immunohistochemistry and diagnostic sequencing are employed to measure STK11 pathway disruption, there are serious limitations to these methods emphasizing the importance to validate a clinically useful assay. Methods An initial STK11 mutation mRNA signature was generated using cell line data and refined using three large, independent patient databases. The signature was validated as a classifier using The Cancer Genome Anatomy Project (TCGA) LUAD cohort as well as a 442-patient LUAD cohort developed at Moffitt. Finally, the signature was adapted into a NanoString -based format and validated using RNA samples isolated from FFPE tissue blocks corresponding to a cohort of 150 LUAD patients. For comparison, STK11 immunochemistry was also performed. Results The STK11 signature was found to correlate with null mutations identified by exon sequencing in multiple cohorts using both microarray and NanoString formats. While there was a statistically significant correlation between reduced STK11 protein expression by IHC and mutation status, the NanoString-based assay showed superior overall performance with a −0.1588 improvement in area under the curve in receiver-operator characteristic curve analysis (p<0.012). Conclusion The described NanoString-based STK11 assay is a sensitive biomarker to study emerging therapeutic modalities in clinical trials. PMID:26917230

Development and validation of a gene expression-based signature to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma: a retrospective, multicentre, cohort study.

PubMed

Tang, Xin-Ran; Li, Ying-Qin; Liang, Shao-Bo; Jiang, Wei; Liu, Fang; Ge, Wen-Xiu; Tang, Ling-Long; Mao, Yan-Ping; He, Qing-Mei; Yang, Xiao-Jing; Zhang, Yuan; Wen, Xin; Zhang, Jian; Wang, Ya-Qin; Zhang, Pan-Pan; Sun, Ying; Yun, Jing-Ping; Zeng, Jing; Li, Li; Liu, Li-Zhi; Liu, Na; Ma, Jun

2018-03-01

Gene expression patterns can be used as prognostic biomarkers in various types of cancers. We aimed to identify a gene expression pattern for individual distant metastatic risk assessment in patients with locoregionally advanced nasopharyngeal carcinoma. In this multicentre, retrospective, cohort analysis, we included 937 patients with locoregionally advanced nasopharyngeal carcinoma from three Chinese hospitals: the Sun Yat-sen University Cancer Center (Guangzhou, China), the Affiliated Hospital of Guilin Medical University (Guilin, China), and the First People's Hospital of Foshan (Foshan, China). Using microarray analysis, we profiled mRNA gene expression between 24 paired locoregionally advanced nasopharyngeal carcinoma tumours from patients at Sun Yat-sen University Cancer Center with or without distant metastasis after radical treatment. Differentially expressed genes were examined using digital expression profiling in a training cohort (Guangzhou training cohort; n=410) to build a gene classifier using a penalised regression model. We validated the prognostic accuracy of this gene classifier in an internal validation cohort (Guangzhou internal validation cohort, n=204) and two external independent cohorts (Guilin cohort, n=165; Foshan cohort, n=158). The primary endpoint was distant metastasis-free survival. Secondary endpoints were disease-free survival and overall survival. We identified 137 differentially expressed genes between metastatic and non-metastatic locoregionally advanced nasopharyngeal carcinoma tissues. A distant metastasis gene signature for locoregionally advanced nasopharyngeal carcinoma (DMGN) that consisted of 13 genes was generated to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter distant metastasis-free survival (hazard ratio [HR] 4·93, 95% CI 2·99-8·16; p<0·0001), disease-free survival (HR 3·51, 2·43-5·07; p<0·0001), and overall survival (HR 3·22, 2·18-4·76; p<0·0001) than patients with low-risk scores. The prognostic accuracy of DMGN was validated in the internal and external cohorts. Furthermore, among patients with low-risk scores in the combined training and internal cohorts, concurrent chemotherapy improved distant metastasis-free survival compared with those patients who did not receive concurrent chemotherapy (HR 0·40, 95% CI 0·19-0·83; p=0·011), whereas patients with high-risk scores did not benefit from concurrent chemotherapy (HR 1·03, 0·71-1·50; p=0·876). This was also validated in the two external cohorts combined. We developed a nomogram based on the DMGN and other variables that predicted an individual's risk of distant metastasis, which was strengthened by adding Epstein-Barr virus DNA status. The DMGN is a reliable prognostic tool for distant metastasis in patients with locoregionally advanced nasopharyngeal carcinoma and might be able to predict which patients benefit from concurrent chemotherapy. It has the potential to guide treatment decisions for patients at different risk of distant metastasis. The National Natural Science Foundation of China, the National Science & Technology Pillar Program during the Twelfth Five-year Plan Period, the Natural Science Foundation of Guang Dong Province, the National Key Research and Development Program of China, the Innovation Team Development Plan of the Ministry of Education, the Health & Medical Collaborative Innovation Project of Guangzhou City, China, and the Program of Introducing Talents of Discipline to Universities. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mortality patterns and trends among 49,705 U.S.-based women in a petroleum company: update 1979-2000.

PubMed

Huebner, Wendy W; Wojcik, Nancy C; Jorgensen, Gail; Marcella, Susan P; Nicolich, Mark J

2010-01-01

To examine mortality patterns and trends in a cohort of women employed in U.S. operating segments of a petroleum company. Based on human resources databases, we defined a cohort of 49,705 U.S.-based women with at least one day of company employment during 1979 to 2000. These data sources provided demographic and most work history information. Standardized mortality ratios and 95% confidence intervals were calculated for 95 causes of death for the total cohort and with separate analyses by job type and operating segment when numbers allowed. Cohort women have a 25% lower overall death rate than the general U.S. female population comparison. This lower rate is expected in light of the "healthy worker effect" that influences employee studies. Circulatory diseases have a deficit of 40%, and external causes of death and cancer have deficits of 13% and 9%, respectively. For analyses by job type, office/clerical workers have an elevation in ovarian cancer (standardized mortality ratio = 1.40, 95% confidence interval = 1.02 to 1.87), based on 46 deaths, with no work-related patterns. White-collar groups have generally large overall deficits for noncancer causes of death. In contrast, and based on smaller numbers, operators and laborers have elevations of motor vehicle accidents and other external causes of death, and laborers also have elevations of cerebrovascular disease and chronic obstructive pulmonary disease. These variations by job type are probably associated with differences in lifestyle factors. This large mortality surveillance study of women in the petroleum industry provides an opportunity for meaningful analysis of many causes of death. The study found an overall favorable mortality profile and, for a small number of elevations, helped identify possible subgroups for health and safety prevention programs and interventions.

Multi-Cohort Stand Structural Classification: Ground- and LiDAR-based Approaches for Boreal Mixedwood and Black Spruce Forest Types of Northeastern Ontario

NASA Astrophysics Data System (ADS)

Kuttner, Benjamin George

Natural fire return intervals are relatively long in eastern Canadian boreal forests and often allow for the development of stands with multiple, successive cohorts of trees. Multi-cohort forest management (MCM) provides a strategy to maintain such multi-cohort stands that focuses on three broad phases of increasingly complex, post-fire stand development, termed "cohorts", and recommends different silvicultural approaches be applied to emulate different cohort types. Previous research on structural cohort typing has relied upon primarily subjective classification methods; in this thesis, I develop more comprehensive and objective methods for three common boreal mixedwood and black spruce forest types in northeastern Ontario. Additionally, I examine relationships between cohort types and stand age, productivity, and disturbance history and the utility of airborne LiDAR to retrieve ground-based classifications and to extend structural cohort typing from plot- to stand-levels. In both mixedwood and black spruce forest types, stand age and age-related deadwood features varied systematically with cohort classes in support of an age-based interpretation of increasing cohort complexity. However, correlations of stand age with cohort classes were surprisingly weak. Differences in site productivity had a significant effect on the accrual of increasingly complex multi-cohort stand structure in both forest types, especially in black spruce stands. The effects of past harvesting in predictive models of class membership were only significant when considered in isolation of age. As an age-emulation strategy, the three cohort model appeared to be poorly suited to black spruce forests where the accrual of structural complexity appeared to be more a function of site productivity than age. Airborne LiDAR data appear to be particularly useful in recovering plot-based cohort types and extending them to the stand-level. The main gradients of structural variability detected using LiDAR were similar between boreal mixedwood and black spruce forest types; the best LiDAR-based models of cohort type relied upon combinations of tree size, size heterogeneity, and tree density related variables. The methods described here to measure, classify, and predict cohort-related structural complexity assist in translating the conceptual three cohort model to a more precise, measurement-based management system. In addition, the approaches presented here to measure and classify stand structural complexity promise to significantly enhance the detail of structural information in operational forest inventories in support of a wide array of forest management and conservation applications.

[Evidence-based medicine as a fundamental principle of health care management for workers].

PubMed

Amirov, N Kh; Fatkhutdinova, L M

2011-01-01

Evidence-based principles in occupational medicine should include prevention, diagnosis, treatment and rehabilitation. Specific feature of occupational medicine is necessity to prove cause-effect relationships between occupational factor and the disease emerged. Important place is occupied by cohort and intervention studies, systematic reviews and meta-analysis. Information obtained by scientific society should be presented to practical specialists and put into everyday activities.

Causal network analysis of head and neck keloid tissue identifies potential master regulators.

PubMed

Garcia-Rodriguez, Laura; Jones, Lamont; Chen, Kang Mei; Datta, Indrani; Divine, George; Worsham, Maria J

2016-10-01

To generate novel insights and hypotheses in keloid development from potential master regulators. Prospective cohort. Six fresh keloid and six normal skin samples from 12 anonymous donors were used in a prospective cohort study. Genome-wide profiling was done previously on the cohort using the Infinium HumanMethylation450 BeadChip (Illumina, San Diego, CA). The 190 statistically significant CpG islands between keloid and normal tissue mapped to 152 genes (P < .05). The top 10 statistically significant genes (VAMP5, ACTR3C, GALNT3, KCNAB2, LRRC61, SCML4, SYNGR1, TNS1, PLEKHG5, PPP1R13-α, false discovery rate <.015) were uploaded into the Ingenuity Pathway Analysis software's Causal Network Analysis (QIAGEN, Redwood City, CA). To reflect expected gene expression direction in the context of methylation changes, the inverse of the methylation ratio from keloid versus normal tissue was used for the analysis. Causal Network Analysis identified disease-specific master regulator molecules based on downstream differentially expressed keloid-specific genes and expected directionality of expression (hypermethylated vs. hypomethylated). Causal Network Analysis software identified four hierarchical networks that included four master regulators (pyroxamide, tributyrin, PRKG2, and PENK) and 19 intermediate regulators. Causal Network Analysis of differentiated methylated gene data of keloid versus normal skin demonstrated four causal networks with four master regulators. These hierarchical networks suggest potential driver roles for their downstream keloid gene targets in the pathogenesis of the keloid phenotype, likely triggered due to perturbation/injury to normal tissue. NA Laryngoscope, 126:E319-E324, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Historical cohort study of US man-made vitreous fiber production workers: VIII. Exposure-specific job analysis.

PubMed

Quinn, M M; Smith, T J; Youk, A O; Marsh, G M; Stone, R A; Buchanich, J M; Gula, M J

2001-09-01

All jobs held by a cohort of US man-made vitreous fiber production workers were analyzed for airborne fiber exposure. This exposure-specific job analysis was part of an exposure assessment for an epidemiologic study of mortality patterns, with particular focus on respiratory cancer, among 35,145 workers employed in 10 fiberglass and five rock or slag wool plants. The exposure assessment was conducted from the start-up date of each plant (1917 to 1946) to 1990. For the job analysis, 15,465 crude department names and 47,693 crude job titles were grouped into 1668 unique department and job pairs (UDJobs), which represented a job title linked to a specific department within each plant. Every UDJob was evaluated according to a set of job elements related to airborne fiber exposure. The distribution of the cohort person-years by UDJob and the job-exposure elements was then evaluated. The results show the main departments and jobs that employed the workers for each plant. The distribution of person-years varies across the job-exposure elements. The same job title was used in different departments within and across plants. When job titles not linked to departments were evaluated, the values of the job-exposure elements varied considerably across all plants and within plant. (1) exposure misclassification could occur if job title alone were used for the exposure assessment; (2) the job-exposure elements analysis provides an efficient way to identify major job determinants of exposure without relying on the more detailed, resource-intensive task-based approach; and (3) the evaluation of the cohort person-years by UDJobs and job-exposure elements is an effective way to identify which plants, departments, and jobs have sufficient information for making precise risk estimates in the broader epidemiologic study.

Association between Work-Related Stress and Risk for Type 2 Diabetes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

PubMed

Sui, Hua; Sun, Nijing; Zhan, Libin; Lu, Xiaoguang; Chen, Tuo; Mao, Xinyong

2016-01-01

The prevalence of type 2 diabetes is increasing rapidly around the world. Work-related stress is thought to be a major risk factor for type 2 diabetes; however, this association has not been widely studied, and the findings that have been reported are inconsistent. Therefore, we conducted a meta-analysis of prospective cohort studies to explore the association between work-related stress and risk for type 2 diabetes. A systematic literature search and manual search limited to articles published in English were performed to select the prospective cohort studies evaluated the association between work-related stress and risk for type 2 diabetes up to September 2014 from four electronic databases including PubMed, EMBASE, the Cochrane Library and Web of Science. A random-effects model was used to estimate the overall risk. No significant association was found between work-related stress and risk for type 2 diabetes based on meta-analysis of seven prospective cohort studies involving 214,086 participants and 5,511 cases (job demands: relative risk 0.94 [95% confidence interval 0.72-1.23]; decision latitude: relative risk 1.16 [0.85-1.58]; job strain: relative risk 1.12 [.0.95-1.32]). However, an association between work-related stress and risk for type 2 diabetes was observed in women (job strain: relative risk 1.22 [1.01-1.46]) (P = 0.04). A sensitivity analysis conducted by excluding one study in each turn yielded similar results. No publication bias was detected with a funnel plot despite the limited number of studies included in the analysis. The results of this meta-analysis did not confirm a direct association between work-related stress and risk for type 2 diabetes. In subgroup analyses we found job strain was a risk factor for type 2 diabetes in women.

Retrospective return on investment analysis of an electronic treatment adherence device piloted in the Northern Cape Province.

PubMed

Broomhead, Sean; Mars, Maurice

2012-01-01

The return on investment (ROI) for utilizing the SIMpill electronic treatment adherence solution as an adjunct to directly observed treatment short-course (DOTS) is assessed using data from a 2005 pilot of the SIMpill solution among new smear-positive tuberculosis (TB) patients in the Northern Cape Province. The value of this cost minimization analysis (CMA), for use by public health planners in low-resource settings as a precursor to more rigorous assessment, is discussed. The retrospective analysis compares the costs and health outcomes of the DOTS-SIMpill cohort with DOTS-only controls. Hypothetical 5-year cash flows are generated and discounted to estimate net present values (NPVs). Comparison between the DOTS-SIMpill pilot cohort and DOTS-only supported controls, for a hypothetical implementation of 1,000 devices, over 5 years, demonstrates positive ROI for the DOTS-SIMpill cohort based on improved health outcomes and reduced average cost per patient. The net stream is shown to be positive from the first year. Discounted NPV is ZAR 3,255,256 (US$ 493,221) for a cohort that would have started mid 2005 and ZAR 3,747,636 (US$ 487,339) starting mid 2010. This is an ROI of 23% over the 5-year period. The addition of electronic treatment adherence support technology can help to improve TB outcomes and lower average cost per patient by reducing treatment failure and the associated higher cost and burden on limited resources. CMA is an appropriate initial analysis for health planners to highlight options that may justify more sophisticated methods such as cost effectiveness analysis or full cost benefit analysis where a preferred option is immediately revealed. CMA is proposed as a tool for use by public health planners in low-resource settings to evaluate the ROI of treatment adherence technology postpilot and prior to implementation.

Risk stratification for arrhythmic death in an emergency department cohort: a new method of nonlinear PD2i analysis of the ECG

PubMed Central

Skinner, James E; Meyer, Michael; Dalsey, William C; Nester, Brian A; Ramalanjaona, George; O’Neil, Brian J; Mangione, Antoinette; Terregino, Carol; Moreyra, Abel; Weiss, Daniel N; Anchin, Jerry M; Geary, Una; Taggart, Pamela

2008-01-01

Heart rate variability (HRV) reflects both cardiac autonomic function and risk of sudden arrhythmic death (AD). Indices of HRV based on linear stochastic models are independent risk factors for AD in postmyocardial infarction (MI) cohorts. Indices based on nonlinear deterministic models have a higher sensitivity and specificity for predicting AD in retrospective data. A new nonlinear deterministic model, the automated Point Correlation Dimension (PD2i), was prospectively evaluated for prediction of AD. Patients were enrolled (N = 918) in 6 emergency departments (EDs) upon presentation with chest pain and being determined to be at risk of acute MI (AMI) >7%. Brief digital ECGs (>1000 heartbeats, ∼15 min) were recorded and automated PD2i results obtained. Out-of-hospital AD was determined by modified Hinkle-Thaler criteria. All-cause mortality at 1 year was 6.2%, with 3.5% being ADs. Of the AD fatalities, 34% were without previous history of MI or diagnosis of AMI. The PD2i prediction of AD had sensitivity = 96%, specificity = 85%, negative predictive value = 99%, and relative risk >24.2 (p ≤ 0.001). HRV analysis by the time-dependent nonlinear PD2i algorithm can accurately predict risk of AD in an ED cohort and may have both life-saving and resource-saving implications for individual risk assessment. PMID:19209249

Risk of Community-Acquired Pneumonia in Patients with a Diagnosis of Pernicious Anemia: A Population-Based Retrospective Cohort Study

PubMed Central

Almario, Christopher V.; Metz, David C.; Haynes, Kevin; Yang, Yu-Xiao

2015-01-01

Objective Pernicious anemia (PA) is an autoimmune disease that causes achlorhydria or profound hypochlorhydria. We conducted a population-based study to determine whether individuals with PA are at increased risk for community-acquired pneumonia (CAP). Methods We performed a retrospective cohort study using The Health Improvement Network (THIN) from the United Kingdom (1993 to 2009). The eligible study cohort included individuals 18 years of age or older and with at least 1 year of THIN follow-up. The exposed group consisted of individuals with a diagnosis code for PA. The unexposed group consisted of individuals without a diagnosis of PA and was frequency matched with the exposed group with respect to age, sex, and practice site. Cox regression analysis was used to determine the hazard ratio (HR) with 95% confidence interval (CI) for CAP associated with PA, accounting for a comprehensive list of potential confounders. Results The study included 13,605 individuals with PA and 50,586 non-PA subjects. The crude incidence rate of CAP was 9.4 per 1000 person-years for those with PA, versus 6.4 per 1000 person-years for those without PA. The multivariable adjusted HR for CAP associated with PA was 1.18, 95% CI 1.08 – 1.29. Conclusions In this large population-based cohort study, individuals with PA and presumed chronic achlorhydria were at increased risk for CAP. PMID:26225868

Examining mortality risk and rate of ageing among Polish Olympic athletes: a survival follow-up from 1924 to 2012.

PubMed

Lin, Yuhui; Gajewski, Antoni; Poznańska, Anna

2016-04-18

Population-based studies have shown that an active lifestyle reduces mortality risk. Therefore, it has been a longstanding belief that individuals who engage in frequent exercise will experience a slower rate of ageing. It is uncertain whether this widely-accepted assumption holds for intense wear-and-tear. Here, using the 88 years survival follow-up data of Polish Olympic athletes, we report for the first time on whether frequent exercise alters the rate of ageing. Longitudinal survival data of male elite Polish athletes who participated in the Olympic Games from year 1924 to 2010 were used. Deaths occurring before the end of World War II were excluded for reliable estimates. Recruited male elite athletes N=1273 were preassigned to two categorical birth cohorts--Cohort I 1890-1919; Cohort II 1920-1959--and a parametric frailty survival analysis was conducted. An event-history analysis was also conducted to adjust for medical improvements from year 1920 onwards: Cohort II. Our findings suggest (1) in Cohort I, for every threefold reduction in mortality risk, the rate of ageing decelerates by 1%; (2) socioeconomic transitions and interventions contribute to a reduction in mortality risk of 29% for the general population and 50% for Olympic athletes; (3) an optimum benefit gained for reducing the rate of ageing from competitive sports (Cohort I 0.086 (95% CI 0.047 to 0.157) and Cohort II 0.085 (95% CI 0.050 to 0.144)). This study further suggests that intensive physical training during youth should be considered as a factor to improve ageing and mortality risk parameters. 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/

Age-period-cohort analysis of suicides among Japanese 1950-2003: a Bayesian cohort model analysis.

PubMed

Ooe, Yosuke; Ohno, Yuko; Nakamura, Takashi

2009-07-01

The suicide rate in Japan is one of the highest in the world and presents us with a considerable challenge. Demographic statistics show that the number of suicides is on the rise, and at roughly 30,000 people per year have committed suicide since 1998. Suicide trends are not only related to economic boom and bust but also to certain generations and age groups. During the 1950s, there was a remarkably high suicide rate among people in their 20s, and this cohort was identical to that of the middle-age generation in the 1980s. It is important to separately understand both the trend of suicide rates and the numbers analyzed to determine the different factors that influence suicide. These include age, time period, cohort, interaction between age and time period, and changes in population composition. We performed an age-period-cohort analysis of annual trends of suicide rates by age group in Japan using a Bayesian cohort model. With the help of the Nakamura method, we have been able to break down the effects of age, time period, cohort, and the age-by-period interaction. The cohort comprised of people born in the 1930s demonstrated a relatively high suicide rate. Men currently in their 50s also belong to a high suicide rate cohort. Regarding the period effect, business cycles and by-period interaction effect, it became apparent that the high suicide rate among young adults in their early 20s around 1960 was slowing, especially among men. Instead, there was an obvious recent trend for men in their late 50s to have the highest suicide rate. This study confirmed that age-period-cohort analysis can describe these trends of suicide mortality of the Japanese.

PTGER4 gene variant rs76523431 is a candidate risk factor for radiological joint damage in rheumatoid arthritis patients: a genetic study of six cohorts.

PubMed

Rodriguez-Rodriguez, Luis; Ivorra-Cortes, Jose; Carmona, F David; Martín, Javier; Balsa, Alejandro; van Steenbergen, Hanna W; van der Helm-van Mil, Annette H M; González-Álvaro, Isidoro; Fernandez-Gutiérrez, Benjamín

2015-11-05

Prostaglandin E receptor 4 (PTGER4) is implicated in immune regulation and bone metabolism. The aim of this study was to analyze its role in radiological joint damage in rheumatoid arthritis (RA). Six independent cohorts of patients with RA of European or North American descent were included, comprising 1789 patients with 5083 sets of X-rays. The Hospital Clínico San Carlos Rheumatoid Arthritis, Princesa Early Arthritis Register Longitudinal study, and Hospital Universitario de La Paz early arthritis (Spain) cohorts were used as discovery cohorts, and the Leiden Early Arthritis Clinic (The Netherlands), Wichita (United States), and National Databank for Rheumatic Diseases (United States and Canada) cohorts as replication cohorts. First, the PTGER4 rs6896969 single-nucleotide polymorphism (SNP) was genotyped using TaqMan assays and available Illumina Immunochip data and studied in the discovery and replication cohorts. Second, the PTGER4 gene and adjacent regions were analyzed using Immunochip genotyping data in the discovery cohorts. On the basis of pooled p values, linkage disequilibrium structure of the region, and location in regions with transcriptional properties, SNPs were selected for replication. The results from discovery, replication, and overall cohorts were pooled using inverse-variance-weighted meta-analysis. Influence of the polymorphisms on the overall radiological damage (constant effect) and on damage progression over time (time-varying effect) was analyzed. The rs6896969 polymorphism showed a significant association with radiological damage in the constant effect pooled analysis of the discovery cohorts, although no significant association was observed in the replication cohorts or the overall pooled analysis. Regarding the analysis of the PTGER4 region, 976 variants were analyzed in the discovery cohorts. From the constant and time-varying effect analyses, 12 and 20 SNPs, respectively, were selected for replication. Only the rs76523431 variant showed a significant association with radiographic progression in the time-varying effect pooled analysis of the discovery, replication, and overall cohorts. The overall pooled effect size was 1.10 (95 % confidence interval 1.05-1.14, p = 2.10 × 10(-5)), meaning that radiographic yearly progression was 10 % greater for each copy of the minor allele. The PTGER4 gene is a candidate risk factor for radiological progression in RA.

Development and validation of a novel predictive scoring model for microvascular invasion in patients with hepatocellular carcinoma.

PubMed

Zhao, Hui; Hua, Ye; Dai, Tu; He, Jian; Tang, Min; Fu, Xu; Mao, Liang; Jin, Huihan; Qiu, Yudong

2017-03-01

Microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) cannot be accurately predicted preoperatively. This study aimed to establish a predictive scoring model of MVI in solitary HCC patients without macroscopic vascular invasion. A total of 309 consecutive HCC patients who underwent curative hepatectomy were divided into the derivation (n=206) and validation cohort (n=103). A predictive scoring model of MVI was established according to the valuable predictors in the derivation cohort based on multivariate logistic regression analysis. The performance of the predictive model was evaluated in the derivation and validation cohorts. Preoperative imaging features on CECT, such as intratumoral arteries, non-nodular type of HCC and absence of radiological tumor capsule were independent predictors for MVI. The predictive scoring model was established according to the β coefficients of the 3 predictors. Area under receiver operating characteristic (AUROC) of the predictive scoring model was 0.872 (95% CI, 0.817-0.928) and 0.856 (95% CI, 0.771-0.940) in the derivation and validation cohorts. The positive and negative predictive values were 76.5% and 88.0% in the derivation cohort and 74.4% and 88.3% in the validation cohort. The performance of the model was similar between the patients with tumor size ≤5cm and >5cm in AUROC (P=0.910). The predictive scoring model based on intratumoral arteries, non-nodular type of HCC, and absence of the radiological tumor capsule on preoperative CECT is of great value in the prediction of MVI regardless of tumor size. Copyright © 2017 Elsevier B.V. All rights reserved.

A Comparison of Live Classroom Instruction and Internet-Based Lessons for a Preparatory Training Course Delivered to 4th Year Pharmacy Students

NASA Astrophysics Data System (ADS)

Nuffer, Wesley; Duke, Jodi

2013-08-01

To compare the effectiveness of an internet-based training series with a traditional live classroom session in preparing pharmacy students to oversee a diabetes management program in community settings. Two cohorts of students were identified that prepared by utilizing a recorded online training exclusively, and two separate cohorts of students prepared by receiving only live classroom instruction. All students in the four cohorts were given a survey to evaluate the training sessions, and results were analyzed using the analysis of variance statistical test (ANOVA). Preceptors at the sites who interacted with students in all four cohorts were surveyed to evaluate which students appeared more prepared; these data were compared using paired t tests. Final assessment data for students in all four cohorts were analyzed using ANOVA. There were statistical differences between the two live training groups, with the second group finding the training to be more beneficial for preparing them, feeling the training length was appropriate and preferring the live modality for delivery. The two internet training cohorts were similar except for perceptions regarding the length of the online training. Comparing responses from those students who received live training with those receiving internet instruction demonstrated a statistical difference with the live groups rating the trainings as more helpful in preparing them for the clinics, rating the training as necessary, and rating their confidence higher in seeing patients. Preceptors rated the live training statistically higher than online training in preparing students. There was no difference between groups on their final site assessments. Live classroom training appears to be superior to the recorded internet training in preparing pharmacy students to oversee a diabetes management program in community settings.

Exploration of preterm birth rates associated with different models of antenatal midwifery care in Scotland: Unmatched retrospective cohort analysis.

PubMed

Symon, Andrew; Winter, Clare; Cochrane, Lynda

2015-06-01

preterm birth represents a significant personal, clinical, organisational and financial burden. Strategies to reduce the preterm birth rate have had limited success. Limited evidence indicates that certain antenatal care models may offer some protection, although the causal mechanism is not understood. We sought to compare preterm birth rates for mixed-risk pregnant women accessing antenatal care organised at a freestanding midwifery unit (FMU) and mixed-risk pregnant women attending an obstetric unit (OU) with related community-based antenatal care. unmatched retrospective 4-year Scottish cohort analysis (2008-2011) of mixed-risk pregnant women accessing (i) FMU antenatal care (n=1107); (ii) combined community-based and OU antenatal care (n=7567). Data were accessed via the Information and Statistics Division of the NHS in Scotland. Aggregates analysis and binary logistic regression were used to compare the cohorts׳ rates of preterm birth; and of spontaneous labour onset, use of pharmacological analgesia, unassisted vertex birth, and low birth weight. Odds ratios were adjusted for age, parity, deprivation score and smoking status in pregnancy. after adjustment the 'mixed risk' FMU cohort had a statistically significantly reduced risk of preterm birth (5.1% [n=57] versus 7.7% [n=583]; AOR 0.73 [95% CI 0.55-0.98]; p=0.034). Differences in these secondary outcome measures were also statistically significant: spontaneous labour onset (FMU 83.9% versus OU 74.6%; AOR 1.74 [95% CI 1.46-2.08]; p<0.001); minimal intrapartum analgesia (FMU 53.7% versus OU 34.4%; AOR 2.17 [95% CI 1.90-2.49]; p<0.001); spontaneous vertex delivery (FMU 71.9% versus OU 63.5%; AOR 1.46 [95% CI 1.32-1.78]; p<0.001). Incidence of low birth weight was not statistically significant after adjustment for other variables. There was no significant difference in the rate of perinatal or neonatal death. given this study׳s methodological limitations, we can only claim associations between the care model and or chosen outcomes. Although both cohorts were mixed risk, differences in risk levels could have contributed to these findings. Nevertheless, the significant difference in preterm birth rates in this study resonates with other research, including the recent Cochrane review of midwife-led continuity models. Because of the multiplicity of risk factors for preterm birth we need to explore the salient features of the FMU model which may be contributing to this apparent protective effect. Because a randomised controlled trial would necessarily restrict choice to pregnant women, we feel that this option is problematic in exploring this further. We therefore plan to conduct a prospective matched cohort analysis together with a survey of unit practices and experiences. Copyright © 2015 Elsevier Ltd. All rights reserved.

From Value Assessment to Value Cocreation: Informing Clinical Decision-Making with Medical Claims Data.

PubMed

Thompson, Steven; Varvel, Stephen; Sasinowski, Maciek; Burke, James P

2016-09-01

Big data and advances in analytical processes represent an opportunity for the healthcare industry to make better evidence-based decisions on the value generated by various tests, procedures, and interventions. Value-based reimbursement is the process of identifying and compensating healthcare providers based on whether their services improve quality of care without increasing cost of care or maintain quality of care while decreasing costs. In this article, we motivate and illustrate the potential opportunities for payers and providers to collaborate and evaluate the clinical and economic efficacy of different healthcare services. We conduct a case study of a firm that offers advanced biomarker and disease state management services for cardiovascular and cardiometabolic conditions. A value-based analysis that comprised a retrospective case/control cohort design was conducted, and claims data for over 7000 subjects who received these services were compared to a matched control cohort. Study subjects were commercial and Medicare Advantage enrollees with evidence of CHD, diabetes, or a related condition. Analysis of medical claims data showed a lower proportion of patients who received biomarker testing and disease state management services experienced a MI (p < 0.01) or diabetic complications (p < 0.001). No significant increase in cost of care was found between the two cohorts. Our results illustrate the opportunity healthcare payers such as Medicare and commercial insurance companies have in terms of identifying value-creating healthcare interventions. However, payers and providers also need to pursue system integration efforts to further automate the identification and dissemination of clinically and economically efficacious treatment plans to ensure at-risk patients receive the treatments and interventions that will benefit them the most.

Risk of colorectal cancer and small bowel adenocarcinoma in Crohn's disease: a population-based study from western Hungary 1977-2008.

PubMed

Lakatos, Peter Laszlo; David, Gyula; Pandur, Tunde; Erdelyi, Zsuzsanna; Mester, Gabor; Balogh, Mihaly; Szipocs, Istvan; Molnar, Csaba; Komaromi, Erzsebet; Kiss, Lajos S; Lakatos, Laszlo

2011-04-01

Limited data are available on the incidence and predictors of colorectal (CRC) and small bowel adenocarcinoma (SBA) in patients with Crohn's disease (CD) from population-based cohorts. Since data are completely missing from Eastern Europe, our aim was to analyze the incidence and risk factors of CD associated CRC and SBA in the population-based, Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008. The data of 506 incident CD patients were analyzed (age-at-diagnosis: 31.5, SD: 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. CRC was diagnosed in five patients (5/5758 person-year-duration) during follow-up, while no patients developed SBA in this cohort. Standardized incidence ratio (SIR) of CRC was not increased overall with five cases observed vs. 5.02 expected (SIR: 0.99, 95% CI: 0.41-2.39); however, there was a tendency for increased incidence in males (five cases observed vs. 2.56 expected; SIR: 1.95, 95% CI: 0.81-4.70). Age at onset of CD (p<0.001), male gender (p=0.022) and stenosing disease behavior at diagnosis (p<0.001) but not disease location were identified as risk factors for developing CRC in univariate analysis and Kaplan-Meier analysis. The cumulative risk for developing CRC after a disease duration of 20 years was 1.1% (95% CI: 0.6-1.7%). The incidence of CRC and SBA was not increased in this population-based CD cohort. Age at onset of CD, male gender and stenosing disease behavior at diagnosis were identified as risk factors of CRC. Copyright © 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

The incidence and prevalence of pterygium in South Korea: A 10-year population-based Korean cohort study.

PubMed

Rim, Tyler Hyungtaek; Kang, Min Jae; Choi, Moonjung; Seo, Kyoung Yul; Kim, Sung Soo

2017-01-01

Although numerous population-based studies have reported the prevalences and risk factors for pterygium, information regarding the incidence of pterygium is scarce. This population-based cohort study aimed to evaluate the South Korean incidence and prevalence of pterygium. We retrospectively obtained data from a nationally representative sample of 1,116,364 South Koreans in the Korea National Health Insurance Service National Sample Cohort (NHIS-NSC). The associated sociodemographic factors were evaluated using multivariable Cox regression analysis, and the hazard ratios and confidence intervals were calculated. Pterygium was defined based on the Korean Classification of Diseases code, and surgically removed pterygium was defined as cases that required surgical removal. We identified 21,465 pterygium cases and 8,338 surgically removed pterygium cases during the study period. The overall incidences were 2.1 per 1,000 person-years for pterygium and 0.8 per 1,000 person-years for surgically removed pterygium. Among subjects who were ≥40 years old, the incidences were 4.3 per 1,000 person-years for pterygium and 1.7 per 1,000 person-years for surgically removed pterygium. The overall prevalences were 1.9% for pterygium and 0.6% for surgically removed pterygium, and the prevalences increased to 3.8% for pterygium and 1.4% for surgically removed pterygium among subjects who were ≥40 years old. The incidences of pterygium decreased according to year. The incidence and prevalence of pterygium were highest among 60-79-year-old individuals. Increasing age, female sex, and living in a relatively rural area were associated with increased risks of pterygium and surgically removed pterygium in the multivariable Cox regression analysis. Our analyses of South Korean national insurance claims data revealed a decreasing trend in the incidence of pterygium during the study period.

Lung Cancer Risk from Plutonium: A Pooled Analysis of the Mayak and Sellafield Worker Cohorts.

PubMed

Gillies, Michael; Kuznetsova, Irina; Sokolnikov, Mikhail; Haylock, Richard; O'Hagan, Jackie; Tsareva, Yulia; Labutina, Elena

2017-12-01

In this study, lung cancer risk from occupational plutonium exposure was analyzed in a pooled cohort of Mayak and Sellafield workers, two of the most informative cohorts in the world with detailed plutonium urine monitoring programs. The pooled cohort comprised 45,817 workers: 23,443 Sellafield workers first employed during 1947-2002 with follow-up until the end of 2005 and 22,374 Mayak workers first employed during 1948-1982 with follow-up until the end of 2008. In the pooled cohort 1,195 lung cancer deaths were observed (789 Mayak, 406 Sellafield) but only 893 lung cancer incidences (509 Mayak, 384 Sellafield, due to truncated follow-up in the incidence analysis). Analyses were performed using Poisson regression models, and were based on doses derived from individual radiation monitoring data using an updated dose assessment methodology developed in the study. There was clear evidence of a linear association between cumulative internal plutonium lung dose and risk of both lung cancer mortality and incidence in the pooled cohort. The pooled point estimates of the excess relative risk (ERR) from plutonium exposure for both lung cancer mortality and incidence were within the range of 5-8 per Gy for males at age 60. The ERR estimates in relationship to external gamma radiation were also significantly raised and in the range 0.2-0.4 per Gy of cumulative gamma dose to the lung. The point estimates of risk, for both external and plutonium exposure, were comparable between the cohorts, which suggests that the pooling of these data was valid. The results support point estimates of relative biological effectiveness (RBE) in the range of 10-25, which is in broad agreement with the value of 20 currently adopted in radiological protection as the radiation weighting factor for alpha particles, however, the uncertainty on this value (RBE = 21; 95% CI: 9-178) is large. The results provide direct evidence that the plutonium risks in each cohort are of the same order of magnitude but the uncertainty on the Sellafield cohort plutonium risk estimates is large, with observed risks consistent with no plutonium risk, and risks five times larger than those observed in the Mayak cohort.

Mediterranean diet adherence during pregnancy and fetal growth: INMA (Spain) and RHEA (Greece) mother-child cohort studies.

PubMed

Chatzi, Leda; Mendez, Michelle; Garcia, Raquel; Roumeliotaki, Theano; Ibarluzea, Jesús; Tardón, Adonina; Amiano, Pilar; Lertxundi, Aitana; Iñiguez, Carmen; Vioque, Jesus; Kogevinas, Manolis; Sunyer, Jordi

2012-01-01

Dietary intake of specific nutrients or food groups during pregnancy could influence fetal growth, but scant evidence is available on effects of dietary patterns. The aim of this study was to evaluate the impact of Mediterranean diet (MD) adherence during pregnancy on fetal growth in two population-based mother-child cohorts in Spain and Greece. We studied 2461 mother-newborn pairs from the Spanish multi-centre 'INMA' study (Atlantic area: INMA-Atlantic; Mediterranean area: INMA-Mediterranean), and 889 pairs from the 'RHEA' study in Crete, Greece. Maternal diet during pregnancy was assessed by FFQ and MD adherence was evaluated through an a priori score. Fetal growth restriction was based on a customised model, and multivariate log-binomial and linear regression models were used to adjust for several confounders. MD scores differ significantly between the cohorts with women in INMA-Atlantic reporting higher intakes of fish and dairy products, while women in the Mediterranean area reported higher intakes of cereals, vegetables and fruits. Women with high MD adherence had a significantly lower risk of delivering a fetal growth-restricted infant for weight (risk ratios: 0·5; 95 % CI 0·3, 0·9) in the INMA-Mediterranean cohort. Stratified analysis by smoking revealed that higher MD adherence increased birth weight and birth length in smoking mothers, whereas this effect was not apparent in non-smoking mothers. The results of the present study show that several types of MD exist across European Mediterranean regions. High MD adherence may modify the detrimental effect of smoking on birth size, but overall effects of diet were not universal for the studies in this analysis.

The Integrated Comprehensive Care Program: A Novel Home Care Initiative After Major Thoracic Surgery.

PubMed

Shargall, Yaron; Hanna, Wael C; Schneider, Laura; Schieman, Colin; Finley, Christian J; Tran, Anna; Demay, Shantel; Gosse, Carolyn; Bowen, James M; Blackhouse, Gord; Smith, Kevin

2016-01-01

The objective of the study was to evaluate the Integrated Comprehensive Care (ICC) program, a novel health system integration initiative that coordinates home care and hospital-based clinical services for patients undergoing major thoracic surgery relative to traditional home care delivery. Methods included a pilot retrospective cohort analysis that compared the intervention cohort (ICC), composed of all patients undergoing major thoracic surgery in the 2012-2013 fiscal year with a control cohort, who underwent surgery in the year before the initiation of ICC. Length of stay, hospital costs, readmission, and emergency room visit data were stratified by degree and approach of resection and compared using univariate logistic regression analysis. A total of 331 patients under ICC and 355 control patients were enrolled. Hospital stay was significantly shorter in patients under video-assisted thoracoscopic surgery (VATS) ICC (sublobar median 3 vs 4 days, P = 0.013; lobar median 4 vs 5 days, P = 0.051) but not for open resections. The frequency of emergency room visits within 60 days of surgery was lower for all stratification groups in the ICC cohort, except for VATS sublobar (25.7% control vs 13.9% ICC, P = 0.097). There were no significant differences in 60-day readmission frequency in any subcohort. The mean inpatient case cost was significantly lower for ICC VATS sublobar resections ($8505.39 vs $11,038.18, P = 0.007), with the other resection types trending lower for ICC but nonsignificant. In conclusion, a hospital-based, postdischarge, patient-centered program could potentially result in shorter hospital stay, fewer readmission and emergency room visits, costsavings, and no increase in adverse postdischarge outcomes after major thoracic surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Genome-wide association uncovers shared genetic effects among personality traits and mood states.

PubMed

Luciano, Michelle; Huffman, Jennifer E; Arias-Vásquez, Alejandro; Vinkhuyzen, Anna A E; Middeldorp, Christel M; Giegling, Ina; Payton, Antony; Davies, Gail; Zgaga, Lina; Janzing, Joost; Ke, Xiayi; Galesloot, Tessel; Hartmann, Annette M; Ollier, William; Tenesa, Albert; Hayward, Caroline; Verhagen, Maaike; Montgomery, Grant W; Hottenga, Jouke-Jan; Konte, Bettina; Starr, John M; Vitart, Veronique; Vos, Pieter E; Madden, Pamela A F; Willemsen, Gonneke; Konnerth, Heike; Horan, Michael A; Porteous, David J; Campbell, Harry; Vermeulen, Sita H; Heath, Andrew C; Wright, Alan; Polasek, Ozren; Kovacevic, Sanja B; Hastie, Nicholas D; Franke, Barbara; Boomsma, Dorret I; Martin, Nicholas G; Rujescu, Dan; Wilson, James F; Buitelaar, Jan; Pendleton, Neil; Rudan, Igor; Deary, Ian J

2012-09-01

Measures of personality and psychological distress are correlated and exhibit genetic covariance. We conducted univariate genome-wide SNP (~2.5 million) and gene-based association analyses of these traits and examined the overlap in results across traits, including a prediction analysis of mood states using genetic polygenic scores for personality. Measures of neuroticism, extraversion, and symptoms of anxiety, depression, and general psychological distress were collected in eight European cohorts (n ranged 546-1,338; maximum total n = 6,268) whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results was performed, with follow-up associations of the top SNPs and genes investigated in independent cohorts (n = 527-6,032). Suggestive association (P = 8 × 10(-8)) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P < 6.09 × 10(-6)) included SNPs in five genes for neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and NOS1 for general psychological distress. An association between symptoms of depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two independent samples, but other replication findings were less consistent. Gene-based tests identified a significant locus on chromosome 15 (spanning five genes) associated with neuroticism which replicated (P < 0.05) in an independent cohort. Support for common genetic effects among personality and mood (particularly neuroticism and depressive symptoms) was found in terms of SNP association overlap and polygenic score prediction. The variance explained by individual SNPs was very small (up to 1%) confirming that there are no moderate/large effects of common SNPs on personality and related traits. Copyright © 2012 Wiley Periodicals, Inc.

Pathway-based discovery of genetic interactions in breast cancer

PubMed Central

Xu, Zack Z.; Boone, Charles; Lange, Carol A.

2017-01-01

Breast cancer is the second largest cause of cancer death among U.S. women and the leading cause of cancer death among women worldwide. Genome-wide association studies (GWAS) have identified several genetic variants associated with susceptibility to breast cancer, but these still explain less than half of the estimated genetic contribution to the disease. Combinations of variants (i.e. genetic interactions) may play an important role in breast cancer susceptibility. However, due to a lack of statistical power, the current tests for genetic interactions from GWAS data mainly leverage prior knowledge to focus on small sets of genes or SNPs that are known to have an association with breast cancer. Thus, many genetic interactions, particularly among novel variants, remain understudied. Reverse-genetic interaction screens in model organisms have shown that genetic interactions frequently cluster into highly structured motifs, where members of the same pathway share similar patterns of genetic interactions. Based on this key observation, we recently developed a method called BridGE to search for such structured motifs in genetic networks derived from GWAS studies and identify pathway-level genetic interactions in human populations. We applied BridGE to six independent breast cancer cohorts and identified significant pathway-level interactions in five cohorts. Joint analysis across all five cohorts revealed a high confidence consensus set of genetic interactions with support in multiple cohorts. The discovered interactions implicated the glutathione conjugation, vitamin D receptor, purine metabolism, mitotic prometaphase, and steroid hormone biosynthesis pathways as major modifiers of breast cancer risk. Notably, while many of the pathways identified by BridGE show clear relevance to breast cancer, variants in these pathways had not been previously discovered by traditional single variant association tests, or single pathway enrichment analysis that does not consider SNP-SNP interactions. PMID:28957314

Cohort profile: the chronic kidney disease prognosis consortium.

PubMed

Matsushita, Kunihiro; Ballew, Shoshana H; Astor, Brad C; Jong, Paul E de; Gansevoort, Ron T; Hemmelgarn, Brenda R; Levey, Andrew S; Levin, Adeera; Wen, Chi-Pang; Woodward, Mark; Coresh, Josef

2013-12-01

The Chronic Kidney Disease Prognosis Consortium (CKD-PC) was established in 2009 to provide comprehensive evidence about the prognostic impact of two key kidney measures that are used to define and stage CKD, estimated glomerular filtration rate (eGFR) and albuminuria, on mortality and kidney outcomes. CKD-PC currently consists of 46 cohorts with data on these kidney measures and outcomes from >2 million participants spanning across 40 countries/regions all over the world. CKD-PC published four meta-analysis articles in 2010-11, providing key evidence for an international consensus on the definition and staging of CKD and an update for CKD clinical practice guidelines. The consortium continues to work on more detailed analysis (subgroups, different eGFR equations, other exposures and outcomes, and risk prediction). CKD-PC preferably collects individual participant data but also applies a novel distributed analysis model, in which each cohort runs statistical analysis locally and shares only analysed outputs for meta-analyses. This distributed model allows inclusion of cohorts which cannot share individual participant level data. According to agreement with cohorts, CKD-PC will not share data with third parties, but is open to including further eligible cohorts. Each cohort can opt in/out for each topic. CKD-PC has established a productive and effective collaboration, allowing flexible participation and complex meta-analyses for studying CKD.

Comparison of Prediction Models for Lynch Syndrome Among Individuals With Colorectal Cancer

PubMed Central

Ojha, Rohit P.; Leenen, Celine; Alvero, Carmelita; Mercado, Rowena C.; Balmaña, Judith; Valenzuela, Irene; Balaguer, Francesc; Green, Roger; Lindor, Noralane M.; Thibodeau, Stephen N.; Newcomb, Polly; Win, Aung Ko; Jenkins, Mark; Buchanan, Daniel D.; Bertario, Lucio; Sala, Paola; Hampel, Heather; Syngal, Sapna; Steyerberg, Ewout W.

2016-01-01

Background: Recent guidelines recommend the Lynch Syndrome prediction models MMRPredict, MMRPro, and PREMM1,2,6 for the identification of MMR gene mutation carriers. We compared the predictive performance and clinical usefulness of these prediction models to identify mutation carriers. Methods: Pedigree data from CRC patients in 11 North American, European, and Australian cohorts (6 clinic- and 5 population-based sites) were used to calculate predicted probabilities of pathogenic MLH1, MSH2, or MSH6 gene mutations by each model and gene-specific predictions by MMRPro and PREMM1,2,6. We examined discrimination with area under the receiver operating characteristic curve (AUC), calibration with observed to expected (O/E) ratio, and clinical usefulness using decision curve analysis to select patients for further evaluation. All statistical tests were two-sided. Results: Mutations were detected in 539 of 2304 (23%) individuals from the clinic-based cohorts (237 MLH1, 251 MSH2, 51 MSH6) and 150 of 3451 (4.4%) individuals from the population-based cohorts (47 MLH1, 71 MSH2, 32 MSH6). Discrimination was similar for clinic- and population-based cohorts: AUCs of 0.76 vs 0.77 for MMRPredict, 0.82 vs 0.85 for MMRPro, and 0.85 vs 0.88 for PREMM1,2,6. For clinic- and population-based cohorts, O/E deviated from 1 for MMRPredict (0.38 and 0.31, respectively) and MMRPro (0.62 and 0.36) but were more satisfactory for PREMM1,2,6 (1.0 and 0.70). MMRPro or PREMM1,2,6 predictions were clinically useful at thresholds of 5% or greater and in particular at greater than 15%. Conclusions: MMRPro and PREMM1,2,6 can well be used to select CRC patients from genetics clinics or population-based settings for tumor and/or germline testing at a 5% or higher risk. If no MMR deficiency is detected and risk exceeds 15%, we suggest considering additional genetic etiologies for the cause of cancer in the family. PMID:26582061

What is heartburn worth? A cost-utility analysis of management strategies.

PubMed

Heudebert, G R; Centor, R M; Klapow, J C; Marks, R; Johnson, L; Wilcox, C M

2000-03-01

To determine the best treatment strategy for the management of patients presenting with symptoms consistent with uncomplicated heartburn. We performed a cost-utility analysis of 4 alternatives: empirical proton pump inhibitor, empirical histamine2-receptor antagonist, and diagnostic strategies consisting of either esophagogastroduodenoscopy (EGD) or an upper gastrointestinal series before treatment. The time horizon of the model was 1 year. The base case analysis assumed a cohort of otherwise healthy 45-year-old individuals in a primary care practice. Empirical treatment with a proton pump inhibitor was projected to provide the greatest quality-adjusted survival for the cohort. Empirical treatment with a histamine2 receptor antagonist was projected to be the least costly of the alternatives. The marginal cost-effectiveness of using a proton pump inhibitor over a histamine2-receptor antagonist was approximately $10,400 per quality-adjusted life year (QALY) gained in the base case analysis and was less than $50,000 per QALY as long as the utility for heartburn was less than 0.95. Both diagnostic strategies were dominated by proton pump inhibitor alternative. Empirical treatment seems to be the optimal initial management strategy for patients with heartburn, but the choice between a proton pump inhibitor or histamine2-receptor antagonist depends on the impact of heartburn on quality of life.

Prognostic molecular markers with no impact on decision-making: the paradox of gliomas based on a prospective study.

PubMed

Wager, M; Menei, P; Guilhot, J; Levillain, P; Michalak, S; Bataille, B; Blanc, J-L; Lapierre, F; Rigoard, P; Milin, S; Duthe, F; Bonneau, D; Larsen, C-J; Karayan-Tapon, L

2008-06-03

This study assessed the prognostic value of several markers involved in gliomagenesis, and compared it with that of other clinical and imaging markers already used. Four-hundred and sixteen adult patients with newly diagnosed glioma were included over a 3-year period and tumour suppressor genes, oncogenes, MGMT and hTERT expressions, losses of heterozygosity, as well as relevant clinical and imaging information were recorded. This prospective study was based on all adult gliomas. Analyses were performed on patient groups selected according to World Health Organization histoprognostic criteria and on the entire cohort. The endpoint was overall survival, estimated by the Kaplan-Meier method. Univariate analysis was followed by multivariate analysis according to a Cox model. p14(ARF), p16(INK4A) and PTEN expressions, and 10p 10q23, 10q26 and 13q LOH for the entire cohort, hTERT expression for high-grade tumours, EGFR for glioblastomas, 10q26 LOH for grade III tumours and anaplastic oligodendrogliomas were found to be correlated with overall survival on univariate analysis and age and grade on multivariate analysis only. This study confirms the prognostic value of several markers. However, the scattering of the values explained by tumour heterogeneity prevents their use in individual decision-making.

Gene-by-Psychosocial Factor Interactions Influence Diastolic Blood Pressure in European and African Ancestry Populations: Meta-Analysis of Four Cohort Studies.

PubMed

Smith, Jennifer A; Zhao, Wei; Yasutake, Kalyn; August, Carmella; Ratliff, Scott M; Faul, Jessica D; Boerwinkle, Eric; Chakravarti, Aravinda; Diez Roux, Ana V; Gao, Yan; Griswold, Michael E; Heiss, Gerardo; Kardia, Sharon L R; Morrison, Alanna C; Musani, Solomon K; Mwasongwe, Stanford; North, Kari E; Rose, Kathryn M; Sims, Mario; Sun, Yan V; Weir, David R; Needham, Belinda L

2017-12-18

Inter-individual variability in blood pressure (BP) is influenced by both genetic and non-genetic factors including socioeconomic and psychosocial stressors. A deeper understanding of the gene-by-socioeconomic/psychosocial factor interactions on BP may help to identify individuals that are genetically susceptible to high BP in specific social contexts. In this study, we used a genomic region-based method for longitudinal analysis, Longitudinal Gene-Environment-Wide Interaction Studies (LGEWIS), to evaluate the effects of interactions between known socioeconomic/psychosocial and genetic risk factors on systolic and diastolic BP in four large epidemiologic cohorts of European and/or African ancestry. After correction for multiple testing, two interactions were significantly associated with diastolic BP. In European ancestry participants, outward/trait anger score had a significant interaction with the C10orf107 genomic region ( p = 0.0019). In African ancestry participants, depressive symptom score had a significant interaction with the HFE genomic region ( p = 0.0048). This study provides a foundation for using genomic region-based longitudinal analysis to identify subgroups of the population that may be at greater risk of elevated BP due to the combined influence of genetic and socioeconomic/psychosocial risk factors.

Validation of Computerized Automatic Calculation of the Sequential Organ Failure Assessment Score

PubMed Central

Harrison, Andrew M.; Pickering, Brian W.; Herasevich, Vitaly

2013-01-01

Purpose. To validate the use of a computer program for the automatic calculation of the sequential organ failure assessment (SOFA) score, as compared to the gold standard of manual chart review. Materials and Methods. Adult admissions (age > 18 years) to the medical ICU with a length of stay greater than 24 hours were studied in the setting of an academic tertiary referral center. A retrospective cross-sectional analysis was performed using a derivation cohort to compare automatic calculation of the SOFA score to the gold standard of manual chart review. After critical appraisal of sources of disagreement, another analysis was performed using an independent validation cohort. Then, a prospective observational analysis was performed using an implementation of this computer program in AWARE Dashboard, which is an existing real-time patient EMR system for use in the ICU. Results. Good agreement between the manual and automatic SOFA calculations was observed for both the derivation (N=94) and validation (N=268) cohorts: 0.02 ± 2.33 and 0.29 ± 1.75 points, respectively. These results were validated in AWARE (N=60). Conclusion. This EMR-based automatic tool accurately calculates SOFA scores and can facilitate ICU decisions without the need for manual data collection. This tool can also be employed in a real-time electronic environment. PMID:23936639

Association of β-defensin copy number and psoriasis in three cohorts of European origin

PubMed Central

Stuart, Philip E; Hüffmeier, Ulrike; Nair, Rajan P; Palla, Raquel; Tejasvi, Trilokraj; Schalkwijk, Joost; Elder, James T; Reis, Andre; Armour, John AL

2012-01-01

A single previous study has demonstrated significant association of psoriasis with copy number of beta-defensin genes, using DNA from psoriasis cases and controls from Nijmegen and Erlangen. In this study we attempted to replicate that finding in larger new cohorts from Erlangen (N = 2017) and Michigan (N = 5412), using improved methods for beta-defensin copy number determination based on the paralog ratio test (PRT), and enhanced methods of analysis and association testing implemented in the CNVtools resource. We demonstrate that the association with psoriasis found in the discovery sample is maintained after applying improved typing and analysis methods (p = 5.5 × 10−4, OR = 1.25). We also find that the association is replicated in 2616 cases and 2526 controls from Michigan, although at reduced significance (p = 0.014), but not in new samples from Erlangen (1396 cases and 621 controls, p = 0.38). Meta-analysis across all cohorts suggests a nominally significant association (p = 6.6 × 10−3/2 × 10−4) with an effect size (OR = 1.081) much lower than found in the discovery study (OR = 1.32). This reduced effect size and significance on replication is consistent with a genuine but weak association. PMID:22739795

Registry-based analysis of participator representativeness: a source of concern for sickness absence research?

PubMed

Knapstad, Marit; Löve, Jesper; Holmgren, Kristina; Hensing, Gunnel; Øverland, Simon

2016-10-21

Selective participation can bias results in epidemiological surveys. The importance of health status is often suggested as a possible explanation for non-participation but few empirical studies exist. In a population-based study, explicitly focused on sickness absence, health and work, we examined whether a history of high levels of sickness absence was associated with non-participation. The study is based on data from official sickness absence registers from participants, non-participants and the total target population of the baseline survey of the Health Assets Project (HAP). HAP is a population-based cohort study in the Västra Götaland region in South Western Sweden. HAP included a random population cohort (n=7984) and 2 cohorts with recent sickness absence (employees (n=6140) and non-employees (n=990)), extracted from the same overall general working-age population. We examined differences in participation rates between cohorts (2008), and differences in previous sickness absence (2001-2008) between participants (individual-level data) and non-participants or the target population (group-level data) within cohorts. Participants had statistically significant less registered sickness absence in the past than non-participants and the target population for some, but not all, of the years analysed. Yet these differences were not of substantial size. Other factors than sickness absence were more important in explaining differences in participation, whereby participants were more likely to be women, older, born in Nordic countries, married and have higher incomes than non-participants. Although specifically addressing sickness absence, having such experience did not add any substantial layer to selective participation in the present survey. Detailed measures are needed to gain a better understanding for health selection in health-related surveys such as those addressing sickness absence, for instance in order to discriminate between selection due to ability or motivation for participation. 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/.

Biopsychosocial influence on shoulder pain: risk subgroups translated across preclinical and clinical prospective cohorts

PubMed Central

George, Steven Z.; Wallace, Margaret R.; Wu, Samuel S.; Moser, Michael W.; Wright, Thomas W.; Farmer, Kevin W.; Borsa, Paul A.; Parr, Jeffrey J.; Greenfield, Warren H.; Dai, Yunfeng; Li, Hua; Fillingim, Roger B.

2016-01-01

Tailored treatment based on individual risk factors is an area with promise to improve options for pain relief. Musculoskeletal pain has a biopsychosocial nature, and multiple factors should be considered when determining risk for chronic pain. This study investigated whether subgroups comprised genetic and psychological factors predicted outcomes in preclinical and clinical models of shoulder pain. Classification and regression tree analysis was performed for an exercise-induced shoulder injury cohort (n = 190) to identify high-risk subgroups, and a surgical pain cohort (n = 150) was used for risk validation. Questionnaires for fear of pain and pain catastrophizing were administered before injury and preoperatively. DNA collected from saliva was genotyped for a priori selected genes involved with pain modulation (COMT and AVPR1A) and inflammation (IL1B and TNF/LTA). Recovery was operationalized as a brief pain inventory rating of 0/10 for current pain intensity and <2/10 for worst pain intensity. Follow-up for the preclinical cohort was in daily increments, whereas follow-up for the clinical cohort was at 3, 6, and 12 months postoperatively. Risk subgroups comprised the COMT high pain sensitivity variant and either pain catastrophizing or fear of pain were predictive of heightened shoulder pain responses in the preclinical model. Further analysis in the clinical model identified the COMT high pain sensitivity variant and pain catastrophizing subgroup as the better predictor. Future studies will determine whether these findings can be replicated in other anatomical regions and whether personalized medicine strategies can be developed for this risk subgroup. PMID:25599310

An algorithm for utilizing peripheral blood CD34 count as a predictor of the need for plerixafor in autologous stem cell mobilization--cost-effectiveness analysis.

PubMed

Abusin, Ghada A; Abu-Arja, Rolla F; Gingrich, Roger D; Silverman, Margarida D; Zamba, Gideon K D; Schlueter, Annette J

2013-08-01

Certain patients who receive granulocyte colony-stimulating factor (GCSF) for autologous hematopoietic stem cell (AHSC) collection fail to mobilize well enough to proceed with transplant. When plerixafor is used with GCSF, the likelihood of achieving the CD34⁺ stem cell target in fewer collections is higher; plerixafor use in all patients is unlikely to be cost-effective. This study retrospectively evaluated the effectiveness of utilizing a peripheral blood CD34⁺ stem cell count (PBCD34) ≤8/µL on day 4 of GCSF-based AHSC mobilization as a threshold for plerixafor administration, and compared the efficacy of collection and cost analysis using historical controls. All patients in the study cohort reached their CD34⁺ targets in ≤3 collections. Significantly more patients who received plerixafor + GCSF versus GCSF alone reached their CD34⁺ target in one collection (P = 0.045); however, there were no significant differences in the number of collections or in cumulative product yields. The historical cohort had 10.3% mobilization failures; the number of collections per patient needed to reach the target was significantly higher in the historical cohort versus study cohort (P = 0.001) as was the number of patients requiring more than one collection to reach their target (P = 0.023). However, the average cost per patient was also significantly higher in the study cohort (P = 0.025). Further refinement of the algorithm may reduce the difference in cost between the two mobilization strategies. Copyright © 2013 Wiley Periodicals, Inc.

Clinical and economic impact of herpes zoster vaccination in elderly in Italy.

PubMed

Boccalini, Sara; Alicino, Cristiano; Martinelli, Domenico; Bechini, Angela; Tiscione, Emilia; Pellizzari, Barbara; Prato, Rosa; Icardi, Giancarlo; Iannazzo, Stefania; Bonanni, Paolo

2017-02-01

Herpes zoster (HZ) is a very relevant pathology among elderly people (≥ 60 years of age), with a considerable disease burden and loss of quality of life. In the last years a new vaccine against HZ became available in Italy. Therefore, the Italian decision makers are now confronted with the decision whether that vaccination should be implemented. Pharmaco-economic analyses represent useful tools to value the feasibility of new immunization programs and their sustainability. To this aim, an ad hoc population model was developed in order to value the clinical and economic impact of HZ vaccination program for the elderly in Italy. Particularly, different immunization scenarios were modeled: vaccination of 60 years-old subjects (single cohort strategy), simultaneous vaccination of people aged 60 and 65 years (double cohort strategy) and, lastly, immunization of people aged 60, 65 and 70 years (triple cohort strategy), thus leading to the vaccination of 5, 10 and 15 cohorts during the first 5 years of the program. The mathematical model valued the clinical impact of vaccination on the number of HZ, post-herpetic neuralgia (PHN) and ophthalmic HZ. The results of the analysis show that, in Italy, a cohort-based HZ vaccination program in elderly could have a relevant impact on the reduction of clinical cases and a favorable economic profile for the National Health Service (NHS), as already foreseen in other countries. In addition, further benefits could be obtained when extending the study period beyond the 5-year horizon of our analysis.

DISTMIX: direct imputation of summary statistics for unmeasured SNPs from mixed ethnicity cohorts.

PubMed

Lee, Donghyung; Bigdeli, T Bernard; Williamson, Vernell S; Vladimirov, Vladimir I; Riley, Brien P; Fanous, Ayman H; Bacanu, Silviu-Alin

2015-10-01

To increase the signal resolution for large-scale meta-analyses of genome-wide association studies, genotypes at unmeasured single nucleotide polymorphisms (SNPs) are commonly imputed using large multi-ethnic reference panels. However, the ever increasing size and ethnic diversity of both reference panels and cohorts makes genotype imputation computationally challenging for moderately sized computer clusters. Moreover, genotype imputation requires subject-level genetic data, which unlike summary statistics provided by virtually all studies, is not publicly available. While there are much less demanding methods which avoid the genotype imputation step by directly imputing SNP statistics, e.g. Directly Imputing summary STatistics (DIST) proposed by our group, their implicit assumptions make them applicable only to ethnically homogeneous cohorts. To decrease computational and access requirements for the analysis of cosmopolitan cohorts, we propose DISTMIX, which extends DIST capabilities to the analysis of mixed ethnicity cohorts. The method uses a relevant reference panel to directly impute unmeasured SNP statistics based only on statistics at measured SNPs and estimated/user-specified ethnic proportions. Simulations show that the proposed method adequately controls the Type I error rates. The 1000 Genomes panel imputation of summary statistics from the ethnically diverse Psychiatric Genetic Consortium Schizophrenia Phase 2 suggests that, when compared to genotype imputation methods, DISTMIX offers comparable imputation accuracy for only a fraction of computational resources. DISTMIX software, its reference population data, and usage examples are publicly available at http://code.google.com/p/distmix. dlee4@vcu.edu Supplementary Data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

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

PubMed

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

2012-05-24

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

Caregiving Antecedents of Secure Base Script Knowledge: A Comparative Analysis of Young Adult Attachment Representations

PubMed Central

Steele, Ryan D.; Waters, Theodore E. A.; Bost, Kelly K.; Vaughn, Brian E.; Truitt, Warren; Waters, Harriet S.; Booth-LaForce, Cathryn; Roisman, Glenn I.

2015-01-01

Based on a sub-sample (N = 673) of the NICHD Study of Early Child Care and Youth Development (SECCYD) cohort, this paper reports data from a follow-up assessment at age 18 years on the antecedents of secure base script knowledge, as reflected in the ability to generate narratives in which attachment-related difficulties are recognized, competent help is provided, and the problem is resolved. Secure base script knowledge was (a) modestly to moderately correlated with more well established assessments of adult attachment, (b) associated with mother-child attachment in the first three years of life and with observations of maternal and paternal sensitivity from childhood to adolescence, and (c) partially accounted for associations previously documented in the SECCYD cohort between early caregiving experiences and Adult Attachment Interview states of mind (Booth-LaForce & Roisman, 2014) as well as self-reported attachment styles (Fraley, Roisman, Booth-LaForce, Owen, & Holland, 2013). PMID:25264703

Development and validation of a predictive model for excessive postpartum blood loss: A retrospective, cohort study.

PubMed

Rubio-Álvarez, Ana; Molina-Alarcón, Milagros; Arias-Arias, Ángel; Hernández-Martínez, Antonio

2018-03-01

postpartum haemorrhage is one of the leading causes of maternal morbidity and mortality worldwide. Despite the use of uterotonics agents as preventive measure, it remains a challenge to identify those women who are at increased risk of postpartum bleeding. to develop and to validate a predictive model to assess the risk of excessive bleeding in women with vaginal birth. retrospective cohorts study. "Mancha-Centro Hospital" (Spain). the elaboration of the predictive model was based on a derivation cohort consisting of 2336 women between 2009 and 2011. For validation purposes, a prospective cohort of 953 women between 2013 and 2014 were employed. Women with antenatal fetal demise, multiple pregnancies and gestations under 35 weeks were excluded METHODS: we used a multivariate analysis with binary logistic regression, Ridge Regression and areas under the Receiver Operating Characteristic curves to determine the predictive ability of the proposed model. there was 197 (8.43%) women with excessive bleeding in the derivation cohort and 63 (6.61%) women in the validation cohort. Predictive factors in the final model were: maternal age, primiparity, duration of the first and second stages of labour, neonatal birth weight and antepartum haemoglobin levels. Accordingly, the predictive ability of this model in the derivation cohort was 0.90 (95% CI: 0.85-0.93), while it remained 0.83 (95% CI: 0.74-0.92) in the validation cohort. this predictive model is proved to have an excellent predictive ability in the derivation cohort, and its validation in a latter population equally shows a good ability for prediction. This model can be employed to identify women with a higher risk of postpartum haemorrhage. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of Alcoholic Intoxication on the Risk of Inflammatory Bowel Disease: A Nationwide Retrospective Cohort Study

PubMed Central

Hsu, Tai-Yi; Shih, Hong-Mo; Wang, Yu-Chiao; Lin, Leng-Chieh; He, Guan-Yi; Chen, Chih-Yu; Kao, Chia-Hung; Chen, Chao-Hsien

2016-01-01

Purpose This study investigated whether alcoholic intoxication (AI) increases the risk of inflammatory bowel disease (IBD) by using a population-based database in Taiwan. Methods This retrospective matched-cohort study included 57 611 inpatients with new-onset AI (AI cohort) and 230 444 randomly selected controls (non-AI cohort). Each patient was monitored for 10 years to individually identify those who were subsequently diagnosed with Crohn disease (CD) and ulcerative colitis (UC) during the follow-up period. Cox proportional hazard regression analysis was conducted to determine the risk of IBD in patients with AI compared with controls without AI. Results The incidence rate of IBD during the 10-year follow-up period was 2.69 per 1 000 person-years and 0.49 per 1 000 person-years in the AI and non-AI cohorts, respectively. After adjustment for age, sex, and comorbidity, the AI cohort exhibited a 3.17-fold increased risk of IBD compared with the non-AI cohort (hazard ratio [HR] = 3.17, 95% confidence interval [CI] = 2.19–4.58). Compared with the non-AI cohort, the HRs of CD and UC were 4.40 and 2.33 for the AI cohort, respectively. After stratification for the severity of AI according to the duration of hospital stay, the adjusted HRs exhibited a significant correlation with the severity; the HRs of IBD were 1.76, 6.83, and 19.9 for patients with mild, moderate, and severe AI, respectively (p for the trend < .0001). Conclusion The risk of IBD was higher in patients with AI and increased with the length of hospital stay. PMID:27802288

Age-related patterns in nonmedical prescription opioid use and disorder in the US population at ages 12-34 from 2002 to 2014.

PubMed

Hu, Mei-Chen; Griesler, Pamela; Wall, Melanie; Kandel, Denise B

2017-08-01

To estimate age-related patterns in nonmedical prescription opioid (NMPO) use in the US population and disorder among past-year users at ages 12-34 between 2002 and 2014, controlling for period and birth-cohort effects. Data are from 13 consecutive cross-sectional National Surveys on Drug Use and Health (N=542,556). Synthetic longitudinal cohorts spanning ages 12-34 were created and an age-period-cohort analysis was implemented based on the Intrinsic Estimator algorithm. In every birth cohort, past-year NMPO use increases during adolescence, peaks at ages 18-21, decreases through ages 30-34; disorder among past-year users increases from ages 18-21 through 30-34. Use at ages 12-34 decreased from the 1984-87 birth cohorts to more recently-born cohorts. Peak prevalence of use at ages 18-21 has also decreased, and the rates of increase from ages 14-17 to ages 18-21 are slowing down. Disorder at ages 18-34 increased from the 1976-79 to 1992-95 cohorts, but decreased at ages 12-17 from the 1992-95 to the most recently-born 2000-02 cohorts. The years 2010-2014 were characterized by lower NMPO use but higher disorder than 2002-2009. Increasing NMPO disorder among users aged 18-34 warrants concern. However, declining NMPO use among 12-34 year-olds, a declining rate of increase from adolescence to early adulthood, and a suggestive decline in disorder among the most recent adolescent cohorts may forecast a potential reduction in the public health crisis associated with NMPO drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

The Cost-Effectiveness of Birth-Cohort Screening for Hepatitis C Antibody in U.S. Primary Care Settings

PubMed Central

Rein, David B.; Smith, Bryce D.; Wittenborn, John S.; Lesesne, Sarah B.; Wagner, Laura D.; Roblin, Douglas W.; Patel, Nita; Ward, John W.; Weinbaum, Cindy M.

2017-01-01

Background In the United States, hepatitis C virus (HCV) infection is most prevalent among adults born from 1945 through 1965, and approximately 50% to 75% of infected adults are unaware of their infection. Objective To estimate the cost-effectiveness of birth-cohort screening. Design Cost-effectiveness simulation. Data Sources National Health and Nutrition Examination Survey, U.S. Census, Medicare reimbursement schedule, and published sources. Target Population Adults born from 1945 through 1965 with 1 or more visits to a primary care provider annually. Time Horizon Lifetime. Perspective Societal, health care. Intervention One-time antibody test of 1945–1965 birth cohort. Outcome Measures Numbers of cases that were identified and treated and that achieved a sustained viral response; liver disease and death from HCV; medical and productivity costs; quality-adjusted life-years (QALYs); incremental cost-effectiveness ratio (ICER). Results of Base-Case Analysis Compared with the status quo, birth-cohort screening identified 808 580 additional cases of chronic HCV infection at a screening cost of $2874 per case identified. Assuming that birth-cohort screening was followed by pegylated interferon and ribavirin (PEG-IFN + R) for treated patients, screening increased QALYs by 348 800 and costs by $5.5 billion, for an ICER of $15 700 per QALY gained. Assuming that birth-cohort screening was followed by direct-acting antiviral plus PEG-IFN + R treatment for treated patients, screening increased QALYs by 532 200 and costs by $19.0 billion, for an ICER of $35 700 per QALY saved. Results of Sensitivity Analysis The ICER of birth-cohort screening was most sensitive to sustained viral response of antiviral therapy, the cost of therapy, the discount rate, and the QALY losses assigned to disease states. Limitation Empirical data on screening and direct-acting antiviral treatment in real-world clinical settings are scarce. Conclusion Birth-cohort screening for HCV in primary care settings was cost-effective. Primary Funding Source Division of Viral Hepatitis, Centers for Disease Control and Prevention. PMID:22056542

Cadmium exposure and risk of lung cancer: a meta-analysis of cohort and case-control studies among general and occupational populations.

PubMed

Chen, Cheng; Xun, Pengcheng; Nishijo, Muneko; He, Ka

2016-09-01

The association between cadmium exposure and risk of lung cancer is still unclear. We quantitatively reviewed the observational studies that investigated the association between cadmium exposure and lung cancer risk in both general and occupational populations published through April 2015. The final data set is comprised of three cohort studies in the general population totaling 22,551 participants (354 events) with a mean follow-up of 15 years, five occupational cohort studies including 4205 individuals (180 events) with an average follow-up of 31 years, and three occupational case-control studies including 4740 cases and 6268 controls. Comparing the highest to the lowest category of cadmium exposure, the weighted relative risk and 95% confidence interval of lung cancer in the general population was 1.42 (95% CI (0.91, 2.23)); the weighted risk estimates (95% CIs) of lung cancer in three occupational cohort studies and three case-control studies were 0.68 (95% CI (0.33, 1.41)) and 1.61 (95% CI (0.94, 2.75)), respectively. No linear association was found. When comparing participants exposed to cadmium with non-exposed based on available data, the association became statistically significant. According to findings from this meta-analysis, the possibility that cadmium exposure may increase risk of lung cancer cannot be completely ruled out in either general or occupational population.

Update on the effect of exogenous hormone use on glioma risk in women: a meta-analysis of case-control and cohort studies.

PubMed

Lan, Yu-Long; Wang, Xun; Lou, Jia-Cheng; Ma, Bin-Bin; Xing, Jin-Shan; Zou, Shuang; Zhang, Bo

2018-04-01

Various studies have confirmed the important roles of endogenous hormones in the development of gliomas, while the roles of exogenous hormones remain controversial. Based on case-control studies and cohort studies, a meta-analysis was exerted to explore the effect of two exogenous hormones use (HRT: hormone replacement therapy; OC: oral contraceptives) on glioma risk. 16 eligible studies, including 11 case-control studies and 5 cohort studies, containing 8055027 women, were included in our study. All included studies have reported the relative risks (RRs) or odds ratios (ORs), and 95% confidence intervals (CIs). We use the fixed-effects model to calculate the estimated overall risk. In case-control studies, the risk of glioma was lower in women who had ever been treated with an exogenous hormone than in the control group (HRT: OR 0.91, 95% CI 0.84-0.99; OC: OR 0.99, 95% CI 0.91-1.07). In research of cohort studies, similar results have been obtained (HRT: RR 0.95, 95% CI 0.83-1.08; OC: RR 0.75, 95% CI 0.66-0.84). Our study further confirmed that the use of exogenous hormones has an important impact on the risk of glioma in women. However, more prospective studies are needed to further confirm this conclusion.

Laboratory-based versus non-laboratory-based method for assessment of cardiovascular disease risk: the NHANES I Follow-up Study cohort

PubMed Central

Gaziano, Thomas A; Young, Cynthia R; Fitzmaurice, Garrett; Atwood, Sidney; Gaziano, J Michael

2008-01-01

Summary Background Around 80% of all cardiovascular deaths occur in developing countries. Assessment of those patients at high risk is an important strategy for prevention. Since developing countries have limited resources for prevention strategies that require laboratory testing, we assessed if a risk prediction method that did not require any laboratory tests could be as accurate as one requiring laboratory information. Methods The National Health and Nutrition Examination Survey (NHANES) was a prospective cohort study of 14 407 US participants aged between 25–74 years at the time they were first examined (between 1971 and 1975). Our follow-up study population included participants with complete information on these surveys who did not report a history of cardiovascular disease (myocardial infarction, heart failure, stroke, angina) or cancer, yielding an analysis dataset N=6186. We compared how well either method could predict first-time fatal and non-fatal cardiovascular disease events in this cohort. For the laboratory-based model, which required blood testing, we used standard risk factors to assess risk of cardiovascular disease: age, systolic blood pressure, smoking status, total cholesterol, reported diabetes status, and current treatment for hypertension. For the non-laboratory-based model, we substituted body-mass index for cholesterol. Findings In the cohort of 6186, there were 1529 first-time cardiovascular events and 578 (38%) deaths due to cardiovascular disease over 21 years. In women, the laboratory-based model was useful for predicting events, with a c statistic of 0·829. The c statistic of the non-laboratory-based model was 0·831. In men, the results were similar (0·784 for the laboratory-based model and 0·783 for the non-laboratory-based model). Results were similar between the laboratory-based and non-laboratory-based models in both men and women when restricted to fatal events only. Interpretation A method that uses non-laboratory-based risk factors predicted cardiovascular events as accurately as one that relied on laboratory-based values. This approach could simplify risk assessment in situations where laboratory testing is inconvenient or unavailable. PMID:18342687

RNA-based determination of ESR1 and HER2 expression and response to neoadjuvant chemotherapy.

PubMed

Denkert, C; Loibl, S; Kronenwett, R; Budczies, J; von Törne, C; Nekljudova, V; Darb-Esfahani, S; Solbach, C; Sinn, B V; Petry, C; Müller, B M; Hilfrich, J; Altmann, G; Staebler, A; Roth, C; Ataseven, B; Kirchner, T; Dietel, M; Untch, M; von Minckwitz, G

2013-03-01

Hormone and human epidermal growth factor receptor 2 (HER2) receptors are the most important breast cancer biomarkers, and additional objective and quantitative test methods such as messenger RNA (mRNA)-based quantitative analysis are urgently needed. In this study, we investigated the clinical validity of RT-PCR-based evaluation of estrogen receptor (ESR1) and HER2 mRNA expression. A total of 1050 core biopsies from two retrospective (GeparTrio, GeparQuattro) and one prospective (PREDICT) neoadjuvant studies were evaluated by quantitative RT-PCR for ESR1 and HER2. ESR1 mRNA was significantly predictive for reduced response to neoadjuvant chemotherapy in univariate and multivariate analysis in all three cohorts. The complete pathologically documented response (pathological complete response, pCR) rate for ESR1+/HER2- tumors was 7.3%, 8.0% and 8.6%; for ESR1-/HER2- tumors it was 34.4%, 33.7% and 37.3% in GeparTrio, GeparQuattro and PREDICT, respectively (P < 0.001 in each cohort). In the Kaplan-Meier analysis in GeparTrio patients with ESR1+/HER2- tumors had the best prognosis, compared with ESR1-/HER2- and ESR1-/HER2+ tumors [disease-free survival (DFS): P < 0.0005, overall survival (OS): P < 0.0005]. Our results suggest that mRNA levels of ESR1 and HER2 predict response to neoadjuvant chemotherapy and are significantly associated with long-term outcome. As an additional option to standard immunohistochemistry and gene-array-based analysis, quantitative RT-PCR analysis might be useful for determination of the receptor status in breast cancer.

Evaluation to Redesign a Prototype Officer Data Base for Interdisciplinary Research

DTIC Science & Technology

1992-01-01

accommodate cohort longitudinal research and econometric model testing . Recommendations regarding the adoption of the LOADB were presented. Utilization...commission data sets (Younkman, 1987), and the AIMS data set ( Ramsey & Younkman, 1989). An analysis of selected standardized tests for ROTC screening was...ARI Research Note 92-16 Evaluation to Redesign a Prototype il Officer Data Base for Interdisciplinary Research Dianne D. Younkman and Lori G. Ramsey

A Study of Psychological Distress in Two Cohorts of First-Year Medical Students that Underwent Different Admission Selection Processes

PubMed Central

Yusoff, Muhamad Saiful Bahri; Rahim, Ahmad Fuad Abdul; Baba, Abdul Aziz; Ismail, Shaiful Bahari; Esa, Ab Rahman

2012-01-01

Background: Medical training is often regarded as a stressful period. Studies have previously found that 21.6%–50% of medical students experience significant psychological distress. The present study compared the prevalence and levels of psychological distress between 2 cohorts of first-year medical students that underwent different admission selection processes. Methods: A comparative cross-sectional study was conducted by comparing 2 cohorts of first-year medical students; 1 group (cohort 1) was selected based purely on academic merit (2008/2009 cohort) and the other group (cohort 2) was selected based on academic merit, psychometric assessment, and interview performance (2009/2010 cohort). Their distress levels were measured by the General Health Questionnaire, and scores higher than 3 were considered indicative of significant psychological distress. Results: The prevalence (P = 0.003) and levels (P = 0.001) of psychological distress were significantly different between the 2 cohorts. Cohort 1 had 1.2–3.3 times higher risk of developing psychological distress compared to cohort 2 (P = 0.007). Conclusion: Cohort 2 had better psychological health than cohort 1 and was less likely to develop psychological distress. This study provided evidence of a potential benefit of multimodal student selection based on academic merit, psychometric assessment, and interview performance. This selection process might identify medical students who will maintain better psychological health. PMID:23610547

Association between Recruitment Methods and Attrition in Internet-Based Studies

PubMed Central

Bajardi, Paolo; Paolotti, Daniela; Vespignani, Alessandro; Eames, Ken; Funk, Sebastian; Edmunds, W. John; Turbelin, Clement; Debin, Marion; Colizza, Vittoria; Smallenburg, Ronald; Koppeschaar, Carl; Franco, Ana O.; Faustino, Vitor; Carnahan, AnnaSara; Rehn, Moa; Merletti, Franco; Douwes, Jeroen; Firestone, Ridvan; Richiardi, Lorenzo

2014-01-01

Internet-based systems for epidemiological studies have advantages over traditional approaches as they can potentially recruit and monitor a wider range of individuals in a relatively inexpensive fashion. We studied the association between communication strategies used for recruitment (offline, online, face-to-face) and follow-up participation in nine Internet-based cohorts: the Influenzanet network of platforms for influenza surveillance which includes seven cohorts in seven different European countries, the Italian birth cohort Ninfea and the New Zealand birth cohort ELF. Follow-up participation varied from 43% to 89% depending on the cohort. Although there were heterogeneities among studies, participants who became aware of the study through an online communication campaign compared with those through traditional offline media seemed to have a lower follow-up participation in 8 out of 9 cohorts. There were no clear differences in participation between participants enrolled face-to-face and those enrolled through other offline strategies. An Internet-based campaign for Internet-based epidemiological studies seems to be less effective than an offline one in enrolling volunteers who keep participating in follow-up questionnaires. This suggests that even for Internet-based epidemiological studies an offline enrollment campaign would be helpful in order to achieve a higher participation proportion and limit the cohort attrition. PMID:25490045

Performance of the disease risk score in a cohort study with policy-induced selection bias.

PubMed

Tadrous, Mina; Mamdani, Muhammad M; Juurlink, David N; Krahn, Murray D; Lévesque, Linda E; Cadarette, Suzanne M

2015-11-01

To examine the performance of the disease risk score (DRS) in a cohort study with evidence of policy-induced selection bias. We examined two cohorts of new users of bisphosphonates. Estimates for 1-year hip fracture rates between agents using DRS, exposure propensity scores and traditional multivariable analysis were compared. The results for the cohort with no evidence of policy-induced selection bias showed little variation across analyses (-4.1-2.0%). Analysis of the cohort with evidence of policy-induced selection bias showed greater variation (-13.5-8.1%), with the greatest difference seen with DRS analyses. Our findings suggest that caution may be warranted when using DRS methods in cohort studies with policy-induced selection bias, further research is needed.

Cohort-based income gradients in obesity among U.S. adults.

PubMed

Heo, Jongho; Beck, Audrey N; Lin, Shih-Fan; Marcelli, Enrico; Lindsay, Suzanne; Karl Finch, Brian

2018-03-01

No studies have focused on socioeconomic disparities in obesity within and between cohorts. Our objectives were to examine income gradients in obesity between birth-cohorts (inter-cohort variations) and within each birth-cohort (intra-cohort variations) by gender and race/ethnicity. Our sample includes 56,820 white and black adults from pooled, cross-sectional National Health and Nutrition Examination Surveys (1971-2012). We fit a series of logistic hierarchical Age-Period-Cohort models to control for the effects of age and period, simultaneously. Predicted probabilities of obesity by poverty-to-income ratio were estimated and graphed for 5-year cohort groups from 1901-1990. We also stratified this relationship for four gender and racial/ethnic subgroups. Obesity disparities due to income were weaker for post-World War I and II generations, specifically the mid-1920s and the mid-1940s to 1950s cohorts, than for other cohorts. In contrast, we found greater income gradients in obesity among cohorts from the 1930s to mid-1940s and mid-1960s to 1970s. Moreover, obesity disparities due to income across cohorts vary markedly by gender and race/ethnicity. White women with higher income consistently exhibited a lower likelihood of obesity than those with lower income since early 1900s cohorts; whereas, black men with higher income exhibited higher risks of obesity than those with lower income in most cohorts. Our findings suggest that strategies that address race and/or gender inequalities in obesity should be cognizant of significant historical factors that may be unique to cohorts. Period-based approaches that ignore life-course experiences captured in significant cohort-based experiences may limit the utility of policies and interventions. © 2017 Wiley Periodicals, Inc.

The frequency of replacement of dental restorations may vary based on a number of variables, including type of material, size of the restoration, and caries risk of the patient.

PubMed

Roumanas, Eleni D

2010-03-01

The authors analyzed the dental records of 2780 Navy (cohort 1 = 1078 entered the Navy in 1997) and US Marine Corps recruits (cohort 2 =1053 entered the USMC in 1999-2000; cohort 3 = 649 entered the USMC in 2002-2005). The records were reviewed at 16 US Navy dental treatment facilities at the following time periods: cohort 1, 2001; cohort 2, 2002-2003; and cohort 3, 2005-2006. The mean age of the subjects was 20 years, and 85% were men. Only posterior teeth (not third molars) with amalgam or resin-based composite (including glass ionomer restorations) were evaluated. Teeth that had been restored with more than one material and restorations that did not involve the occlusal surface were excluded. The minimum follow-up time was 2 years with at least 2 periodic exams following the initial exam. The primary factor of interest was the type of restorative material (amalgam versus resin-based composite). Secondary factors included tooth number, number of restored surfaces (single or multiple), and caries risk of the patient. Caries risk status was defined using the Navy Dental Corps Oral Disease Risk Management protocol. The primary outcome measure of interest was the determination of the relative risk of replacement of an initially intact restoration during the subject's first years of military service. Restorations were classified as clinically acceptable or requiring replacement either as a result of new primary caries, secondary caries, defective restorations, or endodontic therapy. At the initial exam, 964 (15.2%) of the amalgam restorations and 199 (17.4%) of the resin-based composites required replacement and were excluded from further analysis. Of the remaining restorations, an additional 14.2% of the amalgam and 16.7% of the composite restorations required replacement during the observation period. The mean follow-up time was 3.0 years (cohort 1, 3.4 years; cohort 2, 3.1 years; cohort 3, 2.3 years). Replacement rates for resin-based composite restorations compared with amalgam were significantly higher owing to all causes (adjusted hazard ratio [HR], 1.28; P < .05) and for replacement owing to restoration failure (adjusted HR, 1.64; P < .01). Multiple surface restorations demonstrated higher rates of replacement than single surface restorations from all causes (adjusted HR, 1.39; P < .01) and for replacement of existing restorations (adjusted HR, 1.82; P < .01). High-caries-risk subjects experienced more than twice the risk of retreatment than did low-caries-risk subjects when considering all replacements (adjusted HR, 2.04; P < .01) and 50% higher risk of replacement of previously restored surfaces (adjusted HR, 1.48; P<.01) Approximately 30% of all posterior restorations required replacement either at the initial or subsequent exams during the observation period. The number of resin-based composite restorations requiring replacement was significantly higher than amalgam restorations. The authors concluded that because of the extra cost, time, and potential for increased frequency of replacement, posterior composite restorations should be limited to restorations of appropriate size and placed under meticulous restorative technique with strict adherence to manufacturer's instructions.

Cohort fertility in Western Europe: comparing fertility trends in recent birth cohorts.

PubMed

Hopflinger, F

1984-01-01

A comparative study of fertility levels among cohorts of women born in 1940, 1945, 1950, 1955, and 1960 in 16 European countries was undertaken using vital statistics data. The average number of live birth/woman for each of the 5 cohorts by age 20, 25, 30, and 35 was computed by cumulating age-specific fertility rates of women born in specific years. Median age at childbirth and completed fertility were estimated for the 3 oldest cohorts (1940, 1945, and 1950). 2 estimations of completed fertility were made. 1 was based on the assumption of a constant age-specific fertility rate, and the other was based on a relational Gompertz model. Where possible cohort fertility was disaggregated by birth order. Since the data for the countries was not fully comparable, it was not possible to use sophisticated analytical techniques. Other limits of the study were that fertility, especially for the more recent cohorts was incomplete, parity specific data was not available for all the countries, and open cohorts rather than closed cohorts were used. The analysis indicated that completed cohort fertility was lower for the 1950 cohort than for the 1940 cohort in all 16 countries. For the 1940 cohort, only Germany's estimated completed fertility was less than 2.00. For the other 15 countries, estimated completed fertility ranged from 2.04 (Finland) to 3.36 (Ireland). For the 1950 cohort, estimated completed fertility was less than 2.00 in 8 of the countries. Estimated completed fertility was lowest in Finland and Switzerland (1.82) and highest in Ireland (3.33). No marked increase in childlessness was observed, and for the 1940 and 1950 cohorts, childlessness did not exceed 20% in any of the countries and was considerably less than 20% in most of the countries. There was a trend toward delayed childbearing in most of the countries. An examination of available parity data for the 1940 and 1950 cohorts lead to the conclusion that the major factor contributing toward the decline in fertility was a decline in 3rd and higher order births. Most countries showed a decline in higher order births, and in some countries the decline was marked. The proportion of 1-child families increased in many countries and was especially high in Germany. The fertility decline may be leveling off in some of the countries. Fertility will probably stablize at a low level in most of the countries. The decline in fertility is due not only to increased contraceptive use but to the growing trend toward secular individualism in European society. The similarities in the fertility declines in all the countries indicates that identical cross national causes are influencing fertility behavior. The 16 countries included iln the study were Austria, Belgium, Denmark, England and Wales, Finland, France, Germany, Greece, Ireland, Italy, Netherlands, Norway, Portugal, Spain, Sweden, and Switzerland.

Clinical evaluation of a combination therapy of imepitoin with phenobarbital in dogs with refractory idiopathic epilepsy.

PubMed

Neßler, Jasmin; Rundfeldt, Chris; Löscher, Wolfgang; Kostic, Draginja; Keefe, Thomas; Tipold, Andrea

2017-01-25

Imepitoin was tested as a combination treatment with phenobarbital in an open-label mono-centre cohort study in dogs with drug-resistant epilepsy. Diagnosis of idiopathic epilepsy was based on clinical findings, magnetic resonance imaging and cerebrospinal fluid analysis. Three cohorts were treated. In cohort A, dogs not responding to phenobarbital with or without established add-on treatment of potassium bromide or levetiracetam were treated add-on with imepitoin, starting at 10 mg/kg BID, with titration allowed to 30 mg/kg BID. In cohort B, the only difference to cohort A was that the starting dose of imepitoin was reduced to 5 mg/kg BID. In cohort C, animals not responding to imepitoin at >20 mg/kg BID were treated with phenobarbital add-on starting at 0.5 mg/kg BID. The add-on treatment resulted in a reduction in monthly seizure frequency (MSF) in all three cohorts. A reduction of ≥50% was obtained in 36-42% of all animals, without significant difference between cohorts. The lower starting dose of 5 mg/kg BID imepitoin was better tolerated, and an up-titration to on average of 15 mg/kg BID was sufficient in cohort A and B. In cohort C, a mean add-on dose of 1.5 mg/kg BID phenobarbital was sufficient to achieve a clinically meaningful effect. Six dogs developed a clinically meaningful increase in MSF of ≥ 50%, mostly in cohort A. Neither imepitoin nor phenobarbital add-on treatment was capable of suppressing cluster seizure activity, making cluster seizure activity an important predictor for drug-resistance. A combination treatment of imepitoin and phenobarbital is a useful treatment option for a subpopulation of dogs with drug-resistant epilepsy, a low starting dose with 5 mg/kg BID is recommended.

Risk of mortality with concomitant use of tamoxifen and selective serotonin reuptake inhibitors: multi-database cohort study.

PubMed

Donneyong, Macarius M; Bykov, Katsiaryna; Bosco-Levy, Pauline; Dong, Yaa-Hui; Levin, Raisa; Gagne, Joshua J

2016-09-30

 To compare differences in mortality between women concomitantly treated with tamoxifen and selective serotonin reuptake inhibitors (SSRIs) that are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) versus tamoxifen and other SSRIs.  Population based cohort study.  Five US databases covering individuals enrolled in private and public health insurance programs from 1995 to 2013.  Two cohorts of women who started taking tamoxifen. In cohort 1, women started taking an SSRI during tamoxifen treatment. In cohort 2, women were already taking an SSRI when they started taking tamoxifen.  All cause mortality in each cohort in women taking SSRIs that are potent inhibitors of CYP2D6 (paroxetine, fluoxetine) versus other SSRIs. Propensity scores were used to match exposure groups in a variable ratio fashion. Results were measured separately for each cohort and combined hazard ratios calculated from Cox regression models across the two cohorts with random effects meta-analysis.  There were 6067 and 8465 new users of tamoxifen in cohorts 1 and 2, respectively. Mean age was 55. A total of 991 and 1014 deaths occurred in cohorts 1 and 2 during a median follow-up of 2.2 (interquartile range 0.9-4.5) and 2.0 (0.8-3.9) years, respectively. The pooled hazard ratio for death for potent inhibitors (rate 58.6/1000 person years) compared with other SSRIs (rate 57.9/1000 person years) across cohorts 1 and 2 was 0.96 (95% confidence interval 0.88 to 1.06). Results were consistent across sensitivity analyses.  Concomitant use of tamoxifen and potent CYP2D6 inhibiting SSRIs versus other SSRIs was not associated with an increased risk of death. 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.

Predictive test for chemotherapy response in resectable gastric cancer: a multi-cohort, retrospective analysis.

PubMed

Cheong, Jae-Ho; Yang, Han-Kwang; Kim, Hyunki; Kim, Woo Ho; Kim, Young-Woo; Kook, Myeong-Cherl; Park, Young-Kyu; Kim, Hyung-Ho; Lee, Hye Seung; Lee, Kyung Hee; Gu, Mi Jin; Kim, Ha Yan; Lee, Jinae; Choi, Seung Ho; Hong, Soonwon; Kim, Jong Won; Choi, Yoon Young; Hyung, Woo Jin; Jang, Eunji; Kim, Hyeseon; Huh, Yong-Min; Noh, Sung Hoon

2018-05-01

Adjuvant chemotherapy after surgery improves survival of patients with stage II-III, resectable gastric cancer. However, the overall survival benefit observed after adjuvant chemotherapy is moderate, suggesting that not all patients with resectable gastric cancer treated with adjuvant chemotherapy benefit from it. We aimed to develop and validate a predictive test for adjuvant chemotherapy response in patients with resectable, stage II-III gastric cancer. In this multi-cohort, retrospective study, we developed through a multi-step strategy a predictive test consisting of two rule-based classifier algorithms with predictive value for adjuvant chemotherapy response and prognosis. Exploratory bioinformatics analyses identified biologically relevant candidate genes in gastric cancer transcriptome datasets. In the discovery analysis, a four-gene, real-time RT-PCR assay was developed and analytically validated in formalin-fixed, paraffin-embedded (FFPE) tumour tissues from an internal cohort of 307 patients with stage II-III gastric cancer treated at the Yonsei Cancer Center with D2 gastrectomy plus adjuvant fluorouracil-based chemotherapy (n=193) or surgery alone (n=114). The same internal cohort was used to evaluate the prognostic and chemotherapy response predictive value of the single patient classifier genes using associations with 5-year overall survival. The results were validated with a subset (n=625) of FFPE tumour samples from an independent cohort of patients treated in the CLASSIC trial (NCT00411229), who received D2 gastrectomy plus capecitabine and oxaliplatin chemotherapy (n=323) or surgery alone (n=302). The primary endpoint was 5-year overall survival. We identified four classifier genes related to relevant gastric cancer features (GZMB, WARS, SFRP4, and CDX1) that formed the single patient classifier assay. In the validation cohort, the prognostic single patient classifier (based on the expression of GZMB, WARS, and SFRP4) identified 79 (13%) of 625 patients as low risk, 296 (47%) as intermediate risk, and 250 (40%) as high risk, and 5-year overall survival for these groups was 83·2% (95% CI 75·2-92·0), 74·8% (69·9-80·1), and 66·0% (60·1-72·4), respectively (p=0·012). The predictive single patient classifier (based on the expression of GZMB, WARS, and CDX1) assigned 281 (45%) of 625 patients in the validation cohort to the chemotherapy-benefit group and 344 (55%) to the no-benefit group. In the predicted chemotherapy-benefit group, 5-year overall survival was significantly improved in those patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (80% [95% CI 73·5-87·1] vs 64·5% [56·8-73·3]; univariate hazard ratio 0·47 [95% CI 0·30-0·75], p=0·0015), whereas no such improvement in 5-year overall survival was observed in the no-benefit group (72·9% [66·5-79·9] in patients who received chemotherapy plus surgery vs 72·5% [65·8-79·9] in patients who only had surgery; 0·93 [0·62-1·38], p=0·71). The predictive single patient classifier groups (chemotherapy benefit vs no-benefit) could predict adjuvant chemotherapy benefit in terms of 5-year overall survival in the validation cohort (p interaction =0·036 in univariate analysis). Similar results were obtained in the internal evaluation cohort. The single patient classifiers validated in this study provide clinically important prognostic information independent of standard risk-stratification methods and predicted chemotherapy response after surgery in two independent cohorts of patients with resectable, stage II-III gastric cancer. The single patient classifiers could complement TNM staging to optimise decision making in patients with resectable gastric cancer who are eligible for adjuvant chemotherapy after surgery. Further validation of these results in prospective studies is warranted. Ministry of ICT and Future Planning; Ministry of Trade, Industry, and Energy; and Ministry of Health and Welfare. Copyright © 2018 Elsevier Ltd. All rights reserved.

Multimodal neural correlates of cognitive control in the Human Connectome Project.

PubMed

Lerman-Sinkoff, Dov B; Sui, Jing; Rachakonda, Srinivas; Kandala, Sridhar; Calhoun, Vince D; Barch, Deanna M

2017-12-01

Cognitive control is a construct that refers to the set of functions that enable decision-making and task performance through the representation of task states, goals, and rules. The neural correlates of cognitive control have been studied in humans using a wide variety of neuroimaging modalities, including structural MRI, resting-state fMRI, and task-based fMRI. The results from each of these modalities independently have implicated the involvement of a number of brain regions in cognitive control, including dorsal prefrontal cortex, and frontal parietal and cingulo-opercular brain networks. However, it is not clear how the results from a single modality relate to results in other modalities. Recent developments in multimodal image analysis methods provide an avenue for answering such questions and could yield more integrated models of the neural correlates of cognitive control. In this study, we used multiset canonical correlation analysis with joint independent component analysis (mCCA + jICA) to identify multimodal patterns of variation related to cognitive control. We used two independent cohorts of participants from the Human Connectome Project, each of which had data from four imaging modalities. We replicated the findings from the first cohort in the second cohort using both independent and predictive analyses. The independent analyses identified a component in each cohort that was highly similar to the other and significantly correlated with cognitive control performance. The replication by prediction analyses identified two independent components that were significantly correlated with cognitive control performance in the first cohort and significantly predictive of performance in the second cohort. These components identified positive relationships across the modalities in neural regions related to both dynamic and stable aspects of task control, including regions in both the frontal-parietal and cingulo-opercular networks, as well as regions hypothesized to be modulated by cognitive control signaling, such as visual cortex. Taken together, these results illustrate the potential utility of multi-modal analyses in identifying the neural correlates of cognitive control across different indicators of brain structure and function. Copyright © 2017 Elsevier Inc. All rights reserved.

Time Spent Walking and Risk of Diabetes in Japanese Adults: The Japan Public Health Center-Based Prospective Diabetes Study.

PubMed

Kabeya, Yusuke; Goto, Atsushi; Kato, Masayuki; Matsushita, Yumi; Takahashi, Yoshihiko; Isogawa, Akihiro; Inoue, Manami; Mizoue, Tetsuya; Tsugane, Shoichiro; Kadowaki, Takashi; Noda, Mitsuhiko

2016-01-01

The association between time spent walking and risk of diabetes was investigated in a Japanese population-based cohort. Data from the Japan Public Health Center-based Prospective Diabetes cohort were analyzed. The surveys of diabetes were performed at baseline and at the 5-year follow-up. Time spent walking per day was assessed using a self-reported questionnaire (<30 minutes, 30 minutes to <1 hour, 1 to <2 hours, or ≥2 hours). A cross-sectional analysis was performed among 26 488 adults in the baseline survey. Logistic regression was used to examine the association between time spent walking and the presence of unrecognized diabetes. We then performed a longitudinal analysis that was restricted to 11 101 non-diabetic adults who participated in both the baseline and 5-year surveys. The association between time spent walking and the incidence of diabetes during the 5 years was examined. In the cross-sectional analysis, 1058 participants had unrecognized diabetes. Those with time spent walking of <30 minutes per day had increased odds of having diabetes in relation to those with time spent walking of ≥2 hours (adjusted odds ratio [OR] 1.23; 95% CI, 1.02-1.48). In the longitudinal analysis, 612 participants developed diabetes during the 5 years of follow-up. However, a significant association between time spent walking and the incidence of diabetes was not observed. Increased risk of diabetes was implied in those with time spent walking of <30 minutes per day, although the longitudinal analysis failed to show a significant result.

Novel health economic evaluation of a vaccination strategy to prevent HPV-related diseases: the BEST study.

PubMed

Favato, Giampiero; Baio, Gianluca; Capone, Alessandro; Marcellusi, Andrea; Costa, Silvano; Garganese, Giorgia; Picardo, Mauro; Drummond, Mike; Jonsson, Bengt; Scambia, Giovanni; Zweifel, Peter; Mennini, Francesco S

2012-12-01

The development of human papillomavirus (HPV)-related diseases is not understood perfectly and uncertainties associated with commonly utilized probabilistic models must be considered. The study assessed the cost-effectiveness of a quadrivalent-based multicohort HPV vaccination strategy within a Bayesian framework. A full Bayesian multicohort Markov model was used, in which all unknown quantities were associated with suitable probability distributions reflecting the state of currently available knowledge. These distributions were informed by observed data or expert opinion. The model cycle lasted 1 year, whereas the follow-up time horizon was 90 years. Precancerous cervical lesions, cervical cancers, and anogenital warts were considered as outcomes. The base case scenario (2 cohorts of girls aged 12 and 15 y) and other multicohort vaccination strategies (additional cohorts aged 18 and 25 y) were cost-effective, with a discounted cost per quality-adjusted life-year gained that corresponded to €12,013, €13,232, and €15,890 for vaccination programs based on 2, 3, and 4 cohorts, respectively. With multicohort vaccination strategies, the reduction in the number of HPV-related events occurred earlier (range, 3.8-6.4 y) when compared with a single cohort. The analysis of the expected value of information showed that the results of the model were subject to limited uncertainty (cost per patient = €12.6). This methodological approach is designed to incorporate the uncertainty associated with HPV vaccination. Modeling the cost-effectiveness of a multicohort vaccination program with Bayesian statistics confirmed the value for money of quadrivalent-based HPV vaccination. The expected value of information gave the most appropriate and feasible representation of the true value of this program.

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

PubMed Central

Heinävaara, Sirpa; Sarkeala, Tytti; Anttila, Ahti

2016-01-01

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

Risk of Suicide Attempt in Poststroke Patients: A Population-Based Cohort Study.

PubMed

Harnod, Tomor; Lin, Cheng-Li; Kao, Chia-Hung

2018-01-10

This nationwide population-based cohort study evaluated the risk of and risk factors for suicide attempt in poststroke patients in Taiwan. The poststroke and nonstroke cohorts consisted of 713 690 patients and 1 426 009 controls, respectively. Adults (aged >18 years) who received new stroke diagnoses according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM ; codes 430-438) between 2000 and 2011 were included in the poststroke cohort. We calculated the adjusted hazard ratio for suicide attempt ( ICD-9-CM codes E950-E959) after adjustment for age, sex, monthly income, urbanization level, occupation category, and various comorbidities. Kaplan-Meier analysis was used to measure the cumulative incidence of suicide attempt, and the Fine and Gray method was used as a competing event when estimating death subhazard ratios and 95% confidence intervals between groups. The cumulative incidence of suicide attempt was higher in the poststroke cohort, and the adjusted hazard ratio of suicide attempt was 2.20 (95% confidence interval, 2.04-2.37) compared with that of the controls. The leading risk factors for poststroke suicide attempt were earning low monthly income (<660 US dollars), living in less urbanized regions, doing manual labor, and having a stroke before age 50 years. The attempted suicide risk did not differ significantly between male and female patients in this study. These results convey crucial information to clinicians and governments for preventing suicide attempt in poststroke patients in Taiwan and other Asian countries. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Novel Anthropometry Based on 3D-Bodyscans Applied to a Large Population Based Cohort.

PubMed

Löffler-Wirth, Henry; Willscher, Edith; Ahnert, Peter; Wirkner, Kerstin; Engel, Christoph; Loeffler, Markus; Binder, Hans

2016-01-01

Three-dimensional (3D) whole body scanners are increasingly used as precise measuring tools for the rapid quantification of anthropometric measures in epidemiological studies. We analyzed 3D whole body scanning data of nearly 10,000 participants of a cohort collected from the adult population of Leipzig, one of the largest cities in Eastern Germany. We present a novel approach for the systematic analysis of this data which aims at identifying distinguishable clusters of body shapes called body types. In the first step, our method aggregates body measures provided by the scanner into meta-measures, each representing one relevant dimension of the body shape. In a next step, we stratified the cohort into body types and assessed their stability and dependence on the size of the underlying cohort. Using self-organizing maps (SOM) we identified thirteen robust meta-measures and fifteen body types comprising between 1 and 18 percent of the total cohort size. Thirteen of them are virtually gender specific (six for women and seven for men) and thus reflect most abundant body shapes of women and men. Two body types include both women and men, and describe androgynous body shapes that lack typical gender specific features. The body types disentangle a large variability of body shapes enabling distinctions which go beyond the traditional indices such as body mass index, the waist-to-height ratio, the waist-to-hip ratio and the mortality-hazard ABSI-index. In a next step, we will link the identified body types with disease predispositions to study how size and shape of the human body impact health and disease.

An epidemiological study of petroleum refinery employees.

PubMed Central

Wong, O; Morgan, R W; Bailey, W J; Swencicki, R E; Claxton, K; Kheifets, L

1986-01-01

A cohort study of 14179 current and former Chevron USA employees at the Richmond and El Segundo, California, refineries was conducted. The cohort consisted of everyone working at either refinery for a minimum of one year. The observed mortality of the cohort, by cause, was compared with the expected based on the United States mortality rates, standardised for age, race, sex, and calendar time. Analyses by refinery, job category, hire date, duration of employment, and latency were performed. For the entire cohort, mortality from all causes was 72.4% of that expected, a deficit that was statistically significant. In addition, a significantly lower mortality was found for all forms of cancer combined, digestive cancer, lung cancer, heart disease, non-malignant respiratory disease, diseases of the digestive system, and accidents. Only lymphopoietic cancer showed a pattern of increased risk suggestive of a possible relation to an occupational exposure. The excess appears confined to cancer of lymphatic tissue (not leukaemias) at Richmond, and only among those hired before 1948. A follow up case analysis of the deaths from lymphatic cancer failed to identify a common exposure pattern. Images PMID:3947563

Heritability estimates on resting state fMRI data using ENIGMA analysis pipeline.

PubMed

Adhikari, Bhim M; Jahanshad, Neda; Shukla, Dinesh; Glahn, David C; Blangero, John; Reynolds, Richard C; Cox, Robert W; Fieremans, Els; Veraart, Jelle; Novikov, Dmitry S; Nichols, Thomas E; Hong, L Elliot; Thompson, Paul M; Kochunov, Peter

2018-01-01

Big data initiatives such as the Enhancing NeuroImaging Genetics through Meta-Analysis consortium (ENIGMA), combine data collected by independent studies worldwide to achieve more generalizable estimates of effect sizes and more reliable and reproducible outcomes. Such efforts require harmonized image analyses protocols to extract phenotypes consistently. This harmonization is particularly challenging for resting state fMRI due to the wide variability of acquisition protocols and scanner platforms; this leads to site-to-site variance in quality, resolution and temporal signal-to-noise ratio (tSNR). An effective harmonization should provide optimal measures for data of different qualities. We developed a multi-site rsfMRI analysis pipeline to allow research groups around the world to process rsfMRI scans in a harmonized way, to extract consistent and quantitative measurements of connectivity and to perform coordinated statistical tests. We used the single-modality ENIGMA rsfMRI preprocessing pipeline based on modelfree Marchenko-Pastur PCA based denoising to verify and replicate resting state network heritability estimates. We analyzed two independent cohorts, GOBS (Genetics of Brain Structure) and HCP (the Human Connectome Project), which collected data using conventional and connectomics oriented fMRI protocols, respectively. We used seed-based connectivity and dual-regression approaches to show that the rsfMRI signal is consistently heritable across twenty major functional network measures. Heritability values of 20-40% were observed across both cohorts.

Fish intake and risk of heart failure: A meta-analysis of five prospective cohort studies

PubMed Central

HOU, LI-NA; LI, FEI; ZHOU, YOU; NIE, SHI-HUAI; SU, LIANG; CHEN, PING-AN; TAN, WAN-LONG; XU, DING-LI

2012-01-01

The findings on the association between fish intake and the risk of heart failure (HF) have been inconsistent. The purpose of this study was to clarify this potential association. We searched for relevant studies in the PubMed database through January 2012 and manually reviewed references. Five independent prospective cohort studies involving 5,273 cases and 144,917 participants were included. The summary relative risk estimates (SRRE) based on the highest compared with the lowest category of fish consumption were estimated by variance-based meta-analysis. In addition, we performed sensitivity and dose-response analyses to examine the association. Overall, an absence of an association between fish intake and HF was observed (SRRE=1.00; 95% CI, 0.81–1.24). However, fried fish intake positively associated with HF (SRRE=1.40; 95% CI, 1.22–1.61). In addition, dose-response analysis of fried fish suggested that each increment of six fried fish per month corresponded to a 37% increase of HF rate (RR=1.37; 95% CI, 1.20–1.56). In conclusion, our findings suggest that there is no significant association between fish intake and risk of HF, with the exception of a possible positive correlation with individuals comsuming fried fish, based on a limited number of studies. Future studies are required to confirm these findings. PMID:23181122

Multiple Trajectories of Successful Aging of Older and Younger Cohorts

ERIC Educational Resources Information Center

Hsu, Hui-Chuan; Jones, Bobby L.

2012-01-01

Purpose: The purpose of this study was to apply group-based trajectory analysis to identify multiple successful aging trajectories by multiple indicators and to examine the factors related to successful aging among the elderly population in Taiwan. Design and Methods: Nation-representative longitudinal data collected from 1993 to 2007 and…

Maternal Dietary Patterns and Gestational Diabetes Mellitus in a Multi-Ethnic Asian Cohort: The GUSTO Study.

PubMed

de Seymour, Jamie; Chia, Airu; Colega, Marjorelee; Jones, Beatrix; McKenzie, Elizabeth; Shirong, Cai; Godfrey, Keith; Kwek, Kenneth; Saw, Seang-Mei; Conlon, Cathryn; Chong, Yap-Seng; Baker, Philip; Chong, Mary F F

2016-09-20

Gestational Diabetes Mellitus (GDM) is associated with an increased risk of perinatal morbidity and long term health issues for both the mother and offspring. Previous research has demonstrated associations between maternal diet and GDM development, but evidence in Asian populations is limited. The objective of our study was to examine the cross-sectional relationship between maternal dietary patterns during pregnancy and the risk of GDM in a multi-ethnic Asian cohort. Maternal diet was ascertained using 24-h dietary recalls from participants in the Growing up in Singapore towards healthy outcomes (GUSTO) study-a prospective mother-offspring cohort, and GDM was diagnosed according to 1999 World Health Organisation guidelines. Dietary patterns were identified using factor analysis, and multivariate regression analyses performed to assess the association with GDM. Of 909 participants, 17.6% were diagnosed with GDM. Three dietary patterns were identified: a vegetable-fruit-rice-based-diet, a seafood-noodle-based-diet and a pasta-cheese-processed-meat-diet. After adjusting for confounding variables, the seafood-noodle-based-diet was associated with a lower likelihood of GDM (Odds Ratio (95% Confidence Interval)) = 0.74 (0.59, 0.93). The dietary pattern found to be associated with GDM in our study was substantially different to those reported previously in Western populations.

Genetic and environmental influences on height from infancy to early adulthood: An individual-based pooled analysis of 45 twin cohorts

PubMed Central

Jelenkovic, Aline; Sund, Reijo; Hur, Yoon-Mi; Yokoyama, Yoshie; Hjelmborg, Jacob v. B.; Möller, Sören; Honda, Chika; Magnusson, Patrik K. E.; Pedersen, Nancy L.; Ooki, Syuichi; Aaltonen, Sari; Stazi, Maria A.; Fagnani, Corrado; D’Ippolito, Cristina; Freitas, Duarte L.; Maia, José Antonio; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rebato, Esther; Busjahn, Andreas; Kandler, Christian; Saudino, Kimberly J.; Jang, Kerry L.; Cozen, Wendy; Hwang, Amie E.; Mack, Thomas M.; Gao, Wenjing; Yu, Canqing; Li, Liming; Corley, Robin P.; Huibregtse, Brooke M.; Derom, Catherine A.; Vlietinck, Robert F.; Loos, Ruth J. F.; Heikkilä, Kauko; Wardle, Jane; Llewellyn, Clare H.; Fisher, Abigail; McAdams, Tom A.; Eley, Thalia C.; Gregory, Alice M.; He, Mingguang; Ding, Xiaohu; Bjerregaard-Andersen, Morten; Beck-Nielsen, Henning; Sodemann, Morten; Tarnoki, Adam D.; Tarnoki, David L.; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Burt, S. Alexandra; Klump, Kelly L.; Silberg, Judy L.; Eaves, Lindon J.; Maes, Hermine H.; Krueger, Robert F.; McGue, Matt; Pahlen, Shandell; Gatz, Margaret; Butler, David A.; Bartels, Meike; van Beijsterveldt, Toos C. E. M.; Craig, Jeffrey M.; Saffery, Richard; Dubois, Lise; Boivin, Michel; Brendgen, Mara; Dionne, Ginette; Vitaro, Frank; Martin, Nicholas G.; Medland, Sarah E.; Montgomery, Grant W.; Swan, Gary E.; Krasnow, Ruth; Tynelius, Per; Lichtenstein, Paul; Haworth, Claire M. A.; Plomin, Robert; Bayasgalan, Gombojav; Narandalai, Danshiitsoodol; Harden, K. Paige; Tucker-Drob, Elliot M.; Spector, Timothy; Mangino, Massimo; Lachance, Genevieve; Baker, Laura A.; Tuvblad, Catherine; Duncan, Glen E.; Buchwald, Dedra; Willemsen, Gonneke; Skytthe, Axel; Kyvik, Kirsten O.; Christensen, Kaare; Öncel, Sevgi Y.; Aliev, Fazil; Rasmussen, Finn; Goldberg, Jack H.; Sørensen, Thorkild I. A.; Boomsma, Dorret I.; Kaprio, Jaakko; Silventoinen, Karri

2016-01-01

Height variation is known to be determined by both genetic and environmental factors, but a systematic description of how their influences differ by sex, age and global regions is lacking. We conducted an individual-based pooled analysis of 45 twin cohorts from 20 countries, including 180,520 paired measurements at ages 1–19 years. The proportion of height variation explained by shared environmental factors was greatest in early childhood, but these effects remained present until early adulthood. Accordingly, the relative genetic contribution increased with age and was greatest in adolescence (up to 0.83 in boys and 0.76 in girls). Comparing geographic-cultural regions (Europe, North-America and Australia, and East-Asia), genetic variance was greatest in North-America and Australia and lowest in East-Asia, but the relative proportion of genetic variation was roughly similar across these regions. Our findings provide further insights into height variation during childhood and adolescence in populations representing different ethnicities and exposed to different environments. PMID:27333805

Obstetric mode of delivery and attention-deficit/hyperactivity disorder: a sibling-matched study.

PubMed

Curran, Eileen A; Khashan, Ali S; Dalman, Christina; Kenny, Louise C; Cryan, John F; Dinan, Timothy G; Kearney, Patricia M

2016-04-01

It has been suggested that birth by caesarean section (CS) may affect psychological development through changes in microbiota or stress response. We assessed the impact of mode of delivery, specifically CS, on the development of attention-deficit/hyperactivity disorder (ADHD), using a large, population-based cohort. The study cohort consisted of all singleton live births in Sweden from 1990 to 2008 using data from Swedish national registers. Mode of delivery included: unassisted vaginal delivery(VD), assisted VD, elective CS or emergency CS. ADHD was determined using International Classification of Diseases version 10 (F90 or F98.8), or prescription for ADHD medication. We used Cox regression to assess the association between birth by CS and ADHD in the total study population, adjusting for perinatal and sociodemographic factors, then stratified Cox regression analysis on maternal identification number to assess the association among siblings. Our cohort consisted of 1 722 548 children, and among these 47 778 cases of ADHD. The hazard ratio (HR) of the association between elective CS, compared with unassisted VD, and ADHD was 1.15 [95% confidence interval (CI): 1.11-1.20] in the cohort, and 1.05 (95% CI: 0.93-1.18) in the stratified analysis. The HR of the association between emergency CS and ADHD was 1.16 (95% CI: 1.12-1.20])in the cohort and 1.13 (95% CI: 1.01-1.26) in the stratified analysis. Birth by CS is associated with a small increased risk of ADHD. However among siblings the association only remained for emergency CS. If this were a causal effect by CS, the association would be expected to persist for both types of CS, suggesting the observed association is due to confounding. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Genome-Wide Association Study of Cardiac Structure and Systolic Function in African Americans: The Candidate Gene Association Resource (CARe) Study

PubMed Central

Fox, Ervin R.; Musani, Solomon K.; Barbalic, Maja; Lin, Honghuang; Yu, Bing; Ogunyankin, Kofo O.; Smith, Nicholas L.; Kutlar, Abdullah; Glazer, Nicole L.; Post, Wendy S.; Paltoo, Dina N.; Dries, Daniel L.; Farlow, Deborah N.; Duarte, Christine W.; Kardia, Sharon L.; Meyers, Kristin J.; Sun, Yan V.; Arnett, Donna K.; Patki, Amit A.; Sha, Jin; Cui, Xiangqui; Samdarshi, Tandaw E.; Penman, Alan D.; Bibbins-Domingo, Kirsten; Bůžková, Petra; Benjamin, Emelia J.; Bluemke, David A.; Morrison, Alanna C.; Heiss, Gerardo; Carr, J. Jeffrey; Tracy, Russell P.; Mosley, Thomas H.; Taylor, Herman A.; Psaty, Bruce M.; Heckbert, Susan R.; Cappola, Thomas P.; Vasan, Ramachandran S.

2013-01-01

Background Using data from four community-based cohorts of African Americans (AA), we tested the association between genome-wide markers (SNPs) and cardiac phenotypes in the Candidate-gene Association REsource (CARe) study. Methods and Results Among 6,765 AA, we related age, sex, height and weight-adjusted residuals for nine cardiac phenotypes (assessed by echocardiogram or MRI) to 2.5 million SNPs genotyped using Genome-Wide Affymetrix Human SNP Array 6.0 (Affy6.0) and the remainder imputed. Within cohort genome-wide association analysis was conducted followed by meta-analysis across cohorts using inverse variance weights (genome-wide significance threshold=4.0 ×10−07). Supplementary pathway analysis was performed. We attempted replication in 3 smaller cohorts of African ancestry and tested look-ups in one consortium of European ancestry (EchoGEN). Across the 9 phenotypes, variants in 4 genetic loci reached genome-wide significance: rs4552931 in UBE2V2 (p=1.43 × 10−07) for left ventricular mass (LVM); rs7213314 in WIPI1 (p=1.68 × 10−07) for LV internal diastolic diameter (LVIDD); rs1571099 in PPAPDC1A (p= 2.57 × 10−08) for interventricular septal wall thickness (IVST); and rs9530176 in KLF5 (p=4.02 × 10−07) for ejection fraction (EF). Associated variants were enriched in three signaling pathways involved in cardiac remodeling. None of the 4 loci replicated in cohorts of African ancestry were confirmed in look-ups in EchoGEN. Conclusions In the largest GWAS of cardiac structure and function to date in AA, we identified 4 genetic loci related to LVM, IVST, LVIDD and EF that reached genome-wide significance. Replication results suggest that these loci may represent unique to individuals of African ancestry. Additional large-scale studies are warranted for these complex phenotypes. PMID:23275298

Interrogation of the platelet-derived growth factor receptor alpha locus and corneal astigmatism in Australians of Northern European ancestry: results of a genome-wide association study.

PubMed

Yazar, Seyhan; Mishra, Aniket; Ang, Wei; Kearns, Lisa S; Mountain, Jenny A; Pennell, Craig; Montgomery, Grant W; Young, Terri L; Hammond, Christopher J; Macgregor, Stuart; Mackey, David A; Hewitt, Alex W

2013-01-01

Corneal astigmatism is a common eye disorder characterized by irregularities in corneal curvature. Recently, the rs7677751 single nucleotide polymorphism (SNP) at the platelet-derived growth factor receptor alpha (PDGFRA) locus was found to be associated with corneal astigmatism in people of Asian ancestry. In the present study, we sought to replicate this finding and identify other genetic markers of corneal astigmatism in an Australian population of Northern European ancestry. Data from two cohorts were included in this study. The first cohort consisted of 1,013 individuals who were part of the Western Australian Pregnancy Cohort (Raine) Study: 20-year follow-up Eye Study. The second cohort comprised 1,788 individuals of 857 twin families who were recruited through the Twins Eye Study in Tasmania and the Brisbane Adolescent Twin Study. Corneal astigmatism was calculated as the absolute difference between the keratometry readings in two meridians, and genotype data were extracted from genome-wide arrays. Initially, each cohort was analyzed separately, before being combined for meta- and subsequent genome-wide pathway analysis. Following meta-analysis, SNP rs7677751 at the PDGFRA locus had a combined p=0.32. No variant was found to be statistically significantly associated with corneal astigmatism at the genome-wide level (p<5.0×10(-8)). The SNP with strongest association was rs1164064 (p=1.86×10(-6)) on chromosome 3q13. Gene-based pathway analysis identified a significant association between the Gene Ontology "segmentation" (GO:0035282) pathway, corrected p=0.009. Our data suggest that the PDGFRA locus does not transfer a major risk of corneal astigmatism in people of Northern European ancestry. Better-powered studies are required to validate the novel putative findings of our study.

Acquisition of Maternal Education and Its Relation to Single-Word Reading in Middle Childhood: An Analysis of the Millennium Cohort Study

ERIC Educational Resources Information Center

King, Thomas; McKean, Cristina; Rush, Robert; Westrupp, Elizabeth M.; Mensah, Fiona K.; Reilly, Sheena; Law, James

2017-01-01

Maternal education captured at a single time point is commonly employed as a predictor of a child's cognitive development. In this article, we ask what bearing the acquisition of additional qualifications has upon reading performance in middle childhood. This was a secondary analysis of the United Kingdom's Millennium Cohort Study, a cohort of…

T2* Mapping of the Hip in Asymptomatic Volunteers with Normal Cartilage Morphology: An Analysis of Regional and Age-Dependent Distribution.

PubMed

Hesper, Tobias; Schleich, Christoph; Buchwald, Alexander; Hosalkar, Harish S; Antoch, Gerald; Krauspe, Rüdiger; Zilkens, Christoph; Bittersohl, Bernd

2018-01-01

Objective To assess age-dependent and regional differences in T2* relaxation measurements in hip joint cartilage of asymptomatic volunteers at 3 T. Design Three age cohorts (cohort 1: age 20-30 years, 15 individuals; cohort 2: age 30-40 years, 17 individuals; cohort 3: age 40-50 years, 15 individuals) were enrolled. T2* values were obtained in the central and peripheral cartilage of the acetabulum and the femoral head in 7 regions (anterior to superior and posterior). Results T2* did not differ among age cohorts in acetabular cartilage (cohort 1: 24.65 ± 6.56 ms, cohort 2: 24.70 ± 4.83 ms, cohort 3: 25.81 ± 5.10 ms, P = 0.10) and femoral head cartilage (cohort 1: 27.08 ± 8.24 ms, cohort 2: 25.90 ± 7.82 ms, cohort 3: 26.50 ± 5.61 ms, P = 0.34). Analysis of the regional T2* distribution pattern indicates increased T2* values in the anterior, anterior-superior, superior-anterior, and the posterior-superior aspects of acetabular and femoral head cartilage. For acetabular cartilage, higher values were observed in the central region (25.90 ± 4.80 ms vs. 24.21 ± 4.05 ms, P < 0.0001) whereas femoral head cartilage did not reveal such differences (26.62 ± 5.74 ms vs. 26.37 ± 5.89 ms, P = 0.44). Conclusions The T2* analysis of presumably healthy hip joint cartilage does not seem to be stratified according to age in this population. Regional T2* variation throughout hip joint cartilage is apparent in this modality.

Pharmacokinetic and safety profile of tofacitinib in children with polyarticular course juvenile idiopathic arthritis: results of a phase 1, open-label, multicenter study.

PubMed

Ruperto, Nicolino; Brunner, Hermine I; Zuber, Zbigniew; Tzaribachev, Nikolay; Kingsbury, Daniel J; Foeldvari, Ivan; Horneff, Gerd; Smolewska, Elzbieta; Vehe, Richard K; Hazra, Anasuya; Wang, Rong; Mebus, Charles A; Alvey, Christine; Lamba, Manisha; Krishnaswami, Sriram; Stock, Thomas C; Wang, Min; Suehiro, Ricardo; Martini, Alberto; Lovell, Daniel J

2017-12-28

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and a leading cause of childhood disability. The objective of this study was to characterize the PK, safety, and taste acceptability of tofacitinib in patients with JIA. This Phase 1, open-label, multiple-dose (twice daily [BID] for 5 days) study of tofacitinib in patients with active (≥ 5 joints) polyarticular course JIA was conducted from March 2013-December 2015. Patients were allocated to one of three age-based cohorts: Cohort 1, 12 to < 18 years; Cohort 2, 6 to < 12 years; and Cohort 3, 2 to < 6 years. Tofacitinib was administered according to age and body weight as tablets or oral solution (grape flavor). PK were assessed on Day 5; safety was assessed at screening, Day 1, and Day 5. Taste acceptability of the oral solution was evaluated. Twenty-six patients (age range 2-17 years) were enrolled: Cohort 1, N = 8; Cohort 2, N = 9; Cohort 3, N = 9; median tofacitinib doses were 5.0, 2.5, and 3.0 mg BID, respectively. The higher median tofacitinib dose in Cohort 3 versus Cohort 2 reflected implementation of an amended dosing scheme following an interim PK analysis after Cohort 2 recruitment. Geometric mean AUC at steady state (AUC tau ) was 156.6 ng•h/mL in Cohort 1, 118.8 ng•h/mL in Cohort 2, and 142.5 ng•h/mL in Cohort 3; C max (ng/mL) was 47.0, 41.7, and 66.2, respectively. C trough , C min , and t 1/2 were similar in Cohorts 2 and 3, but higher in Cohort 1. Median time to C max (T max ) was similar between cohorts. Apparent clearance and volume of distribution decreased with decreasing age. Tofacitinib was well tolerated, with no serious adverse events or discontinuations due to adverse events reported. Taste acceptability was confirmed. PK findings from this study in children with polyarticular course JIA established dosing regimens and acceptable taste for use in subsequent studies within the tofacitinib pediatric development program. ClinicalTrials.gov: NCT01513902 .

Omega 3 fatty acids for prevention and treatment of cardiovascular disease

PubMed Central

Hooper, Lee; Harrison, Roger A; Summerbell, Carolyn D; Moore, Helen; Worthington, Helen V; Ness, Andrew; Capps, Nigel; Smith, George Davey; Riemersma, Rudolph; Ebrahim, Shah

2014-01-01

Background It has been suggested that omega 3 (W3, n-3 or omega-3) fats from oily fish and plants are beneficial to health. Objectives To assess whether dietary or supplemental omega 3 fatty acids alter total mortality, cardiovascular events or cancers using both RCT and cohort studies. Search methods Five databases including CENTRAL, MEDLINE and EMBASE were searched to February 2002. No language restrictions were applied. Bibliographies were checked and authors contacted. Selection criteria RCTs were included where omega 3 intake or advice was randomly allocated and unconfounded, and study duration was at least six months. Cohorts were included where a cohort was followed up for at least six months and omega 3 intake estimated. Data collection and analysis Studies were assessed for inclusion, data extracted and quality assessed independently in duplicate. Random effects meta-analysis was performed separately for RCT and cohort data. Main results Forty eight randomised controlled trials (36,913 participants) and 41 cohort analyses were included. Pooled trial results did not show a reduction in the risk of total mortality or combined cardiovascular events in those taking additional omega 3 fats (with significant statistical heterogeneity). Sensitivity analysis, retaining only studies at low risk of bias, reduced heterogeneity and again suggested no significant effect of omega 3 fats. Restricting analysis to trials increasing fish-based omega 3 fats, or those increasing short chain omega 3s, did not suggest significant effects on mortality or cardiovascular events in either group. Subgroup analysis by dietary advice or supplementation, baseline risk of CVD or omega 3 dose suggested no clear effects of these factors on primary outcomes. Neither RCTs nor cohorts suggested increased relative risk of cancers with higher omega 3 intake but estimates were imprecise so a clinically important effect could not be excluded. Authors’ conclusions It is not clear that dietary or supplemental omega 3 fats alter total mortality, combined cardiovascular events or cancers in people with, or at high risk of, cardiovascular disease or in the general population. There is no evidence we should advise people to stop taking rich sources of omega 3 fats, but further high quality trials are needed to confirm suggestions of a protective effect of omega 3 fats on cardiovascular health. There is no clear evidence that omega 3 fats differ in effectiveness according to fish or plant sources, dietary or supplemental sources, dose or presence of placebo. PMID:15495044

Validation of the Retinal Detachment after Open Globe Injury (RD-OGI) Score as an Effective Tool for Predicting Retinal Detachment.

PubMed

Brodowska, Katarzyna; Stryjewski, Tomasz P; Papavasileiou, Evangelia; Chee, Yewlin E; Eliott, Dean

2017-05-01

The Retinal Detachment after Open Globe Injury (RD-OGI) Score is a clinical prediction model that was developed at the Massachusetts Eye and Ear Infirmary to predict the risk of retinal detachment (RD) after open globe injury (OGI). This study sought to validate the RD-OGI Score in an independent cohort of patients. Retrospective cohort study. The predictive value of the RD-OGI Score was evaluated by comparing the original RD-OGI Scores of 893 eyes with OGI that presented between 1999 and 2011 (the derivation cohort) with 184 eyes with OGI that presented from January 1, 2012, to January 31, 2014 (the validation cohort). Three risk classes (low, moderate, and high) were created and logistic regression was undertaken to evaluate the optimal predictive value of the RD-OGI Score. A Kaplan-Meier survival analysis evaluated survival experience between the risk classes. Time to RD. At 1 year after OGI, 255 eyes (29%) in the derivation cohort and 66 eyes (36%) in the validation cohort were diagnosed with an RD. At 1 year, the low risk class (RD-OGI Scores 0-2) had a 3% detachment rate in the derivation cohort and a 0% detachment rate in the validation cohort, the moderate risk class (RD-OGI Scores 2.5-4.5) had a 29% detachment rate in the derivation cohort and a 35% detachment rate in the validation cohort, and the high risk class (RD-OGI scores 5-7.5) had a 73% detachment rate in the derivation cohort and an 86% detachment rate in the validation cohort. Regression modeling revealed the RD-OGI to be highly discriminative, especially 30 days after injury, with an area under the receiver operating characteristic curve of 0.939 in the validation cohort. Survival experience was significantly different depending upon the risk class (P < 0.0001, log-rank chi-square). The RD-OGI Score can reliably predict the future risk of developing an RD based on clinical variables that are present at the time of the initial evaluation after OGI. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Using Team-based Learning to Teach a Hybrid Pharmacokinetics Course Online and in Class.

PubMed

Franklin, Ann Snyder; Markowsky, Susan; De Leo, Justin; Normann, Sven; Black, Erik

2016-12-25

Objective. To compare the effectiveness of face-to-face and online team-based learning (TBL) to teach phenytoin pharmacokinetics. Design. A TBL format was used to teach an online cohort of 222 pharmacy students and two face-to-face cohorts (Tampa and Las Vegas) of pharmacy students. Students in all cohorts completed individual and team readiness tests (iRATs and tRATs), and a self-assessment survey to determine teamwork and content understanding. Knowledge retention questions also were added to the final examination. Assessment. Mean scores on iRATs were: 54% for the Tampa group; 72% for the Las Vegas group; and 58% for the online. Mean tRAT scores were 78.5% for the Tampa cohort and 82.2% for the Las Vegas cohort, compared to 89.5% for the online cohort. The mean tRAT scores for the online cohorts were significantly higher than those of the face-to-face cohorts. Data from the teamwork survey provided evidence of positive interactions among teams for all cohorts. Conclusion. Team-based learning can be an effective method for teaching applied pharmacokinetics in both face-to-face and online classes.

Educational expansion and the education gradient in health: A hierarchical age-period-cohort analysis.

PubMed

Delaruelle, Katrijn; Buffel, Veerle; Bracke, Piet

2015-11-01

Researchers have recently been investigating the temporal variation in the educational gradient in health. While there is abundant literature concerning age trajectories, theoretical knowledge about cohort differences is relatively limited. Therefore, in analogy with the life course perspective, we introduce two contrasting cohort-specific hypotheses. The diminishing health returns hypothesis predicts a decrease in educational disparities in health across cohorts. By contrast, the cohort accretion hypothesis suggests that the education-health gap will be more pronounced among younger cohorts. To shed light on this, we perform a hierarchical age-period-cohort analysis (HAPC), using data from a subsample of individuals between 25 and 85 years of age (N = 232,573) from 32 countries in the European Social Survey (six waves: 2002-2012). The analysis leads to three important conclusions. First, we observe a widening health gap between different educational levels over the life course. Second, we find that these educational differences in the age trajectories of health seem to strengthen with each successive birth cohort. However, the two age-related effects disappear when we control for employment status, household income, and family characteristics. Last, when adjusting for these mediators, we reveal evidence to support the diminishing health returns hypothesis, implying that it is primarily the direct association between education and health that decreases across cohorts. This finding raises concerns about potential barriers to education being a vehicle for empowerment and the promotion of health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Palliative care and prognosis in COPD: a systematic review with a validation cohort.

PubMed

Almagro, Pere; Yun, Sergi; Sangil, Ana; Rodríguez-Carballeira, Mónica; Marine, Meritxell; Landete, Pedro; Soler-Cataluña, Juan José; Soriano, Joan B; Miravitlles, Marc

2017-01-01

Current recommendations to consider initiation of palliative care (PC) in COPD patients are often based on an expected poor prognosis. However, this approach is not evidence-based, and which and when COPD patients should start PC is controversial. We aimed to assess whether current suggested recommendations for initiating PC were sufficiently reliable. We identified prognostic variables proposed in the literature for initiating PC; then, we ascertained their relationship with 1-year mortality, and finally, we validated their utility in our cohort of 697 patients hospitalized for COPD exacerbation. From 24 articles of 499 screened, we selected 20 variables and retrieved 48 original articles in which we were able to calculate the relationship between each of them and 1-year mortality. The number of studies where 1-year mortality was detailed for these variables ranged from 9 for previous hospitalizations or FEV 1 ≤30% to none for albumin ≤25 mg/dL. The percentage of 1-year mortality in the literature for these variables ranged from 5% to 60%. In the validation cohort study, the prevalence of these proposed variables ranged from 8% to 64%; only 10 of the 18 variables analyzed in our cohort reached statistical significance with Cox regression analysis, and none overcame an area under the curve ≥0.7. We conclude that none of the suggested criteria for initiating PC based on an expected poor vital prognosis in COPD patients in the short or medium term offers sufficient reliability, and consequently, they should be avoided as exclusive criteria for considering PC or at least critically appraised.

Palliative care and prognosis in COPD: a systematic review with a validation cohort

PubMed Central

Almagro, Pere; Yun, Sergi; Sangil, Ana; Rodríguez-Carballeira, Mónica; Marine, Meritxell; Landete, Pedro; Soler-Cataluña, Juan José; Soriano, Joan B; Miravitlles, Marc

2017-01-01

Current recommendations to consider initiation of palliative care (PC) in COPD patients are often based on an expected poor prognosis. However, this approach is not evidence-based, and which and when COPD patients should start PC is controversial. We aimed to assess whether current suggested recommendations for initiating PC were sufficiently reliable. We identified prognostic variables proposed in the literature for initiating PC; then, we ascertained their relationship with 1-year mortality, and finally, we validated their utility in our cohort of 697 patients hospitalized for COPD exacerbation. From 24 articles of 499 screened, we selected 20 variables and retrieved 48 original articles in which we were able to calculate the relationship between each of them and 1-year mortality. The number of studies where 1-year mortality was detailed for these variables ranged from 9 for previous hospitalizations or FEV1 ≤30% to none for albumin ≤25 mg/dL. The percentage of 1-year mortality in the literature for these variables ranged from 5% to 60%. In the validation cohort study, the prevalence of these proposed variables ranged from 8% to 64%; only 10 of the 18 variables analyzed in our cohort reached statistical significance with Cox regression analysis, and none overcame an area under the curve ≥0.7. We conclude that none of the suggested criteria for initiating PC based on an expected poor vital prognosis in COPD patients in the short or medium term offers sufficient reliability, and consequently, they should be avoided as exclusive criteria for considering PC or at least critically appraised. PMID:28652724

Predictors of Cerebral Palsy in Very Preterm Infants: The EPIPAGE Prospective Population-Based Cohort Study

ERIC Educational Resources Information Center

Beaino, Ghada; Khoshnood, Babak; Kaminski, Monique; Pierrat, Veronique; Marret, Stephane; Matis, Jacqueline; Ledesert, Bernard; Thiriez, Gerard; Fresson, Jeanne; Roze, Jean-Christophe; Zupan-Simunek, Veronique; Arnaud, Catherine; Burguet, Antoine; Larroque, Beatrice; Breart, Gerard; Ancel, Pierre-Yves

2010-01-01

Aim: The aim of this study was to assess the independent role of cerebral lesions on ultrasound scan, and several other neonatal and obstetric factors, as potential predictors of cerebral palsy (CP) in a large population-based cohort of very preterm infants. Method: As part of EPIPAGE, a population-based prospective cohort study, perinatal data…

Developing an Anti-Xa-Based Anticoagulation Protocol for Patients with Percutaneous Ventricular Assist Devices.

PubMed

Sieg, Adam; Mardis, B Andrew; Mardis, Caitlin R; Huber, Michelle R; New, James P; Meadows, Holly B; Cook, Jennifer L; Toole, J Matthew; Uber, Walter E

2015-01-01

Because of the complexities associated with anticoagulation in temporary percutaneous ventricular assist device (pVAD) recipients, a lack of standardization exists in their management. This retrospective analysis evaluates current anticoagulation practices at a single center with the aim of identifying an optimal anticoagulation strategy and protocol. Patients were divided into two cohorts based on pVAD implanted (CentriMag (Thoratec; Pleasanton, CA) / TandemHeart (CardiacAssist; Pittsburgh, PA) or Impella (Abiomed, Danvers, MA)), with each group individually analyzed for bleeding and thrombotic complications. Patients in the CentriMag/TandemHeart cohort were subdivided based on the anticoagulation monitoring strategy (activated partial thromboplastin time (aPTT) or antifactor Xa unfractionated heparin (anti-Xa) values). In the CentriMag/TandemHeart cohort, there were five patients with anticoagulation titrated based on anti-Xa values; one patient developed a device thrombosis and a major bleed, whereas another patient experienced major bleeding. Eight patients received an Impella pVAD. Seven total major bleeds in three patients and no thrombotic events were detected. Based on distinct differences between the devices, anti-Xa values, and outcomes, two protocols were created to guide anticoagulation adjustments. However, anticoagulation in patients who require pVAD support is complex with constantly evolving anticoagulation goals. The ideal level of anticoagulation should be individually determined using several coagulation laboratory parameters in concert with hemodynamic changes in the patient's clinical status, the device, and the device cannulation.

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

PubMed

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

2003-01-01

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

Cost-effectiveness of partially-hydrolyzed formula for prevention of atopic dermatitis in Australia.

PubMed

Su, John; Prescott, Susan; Sinn, John; Tang, Mimi; Smith, Peter; Heine, Ralf G; Spieldenner, Jörg; Iskedjian, Michael

2012-01-01

To perform an economic evaluation of a specific brand of partially hydrolyzed infant formula (PHF-W) in the prevention of atopic dermatitis (AD) among Australian infants. A cost-effectiveness analysis was undertaken from the perspectives of the Department of Health and Aging (DHA), of the family of the affected subject and of society as a whole in Australia, based on a decision-analytic model following a hypothetical representative cohort of Australian newborns who are not exclusively breastfed and who have a familial history of allergic disease (i.e., are deemed 'at risk'). Costs, consequences, and incremental cost-effectiveness ratios (ICER) were calculated for PHF-W vs standard cow's milk based infant formula (SF), and, in a secondary analysis, vs extensively hydrolyzed infant formula (EHF-Whey), when the latter was used for the prevention of AD. From a representative starting cohort of 87,724 'at risk' newborns in Australia in 2009, the expected ICERs for PHF-W vs SF were AU$496 from the perspective of the DHA and savings of AUD1739 and AU$1243 from the family and societal perspectives, respectively. When compared to EHF-Whey, PHF-W was associated with savings for the cohort of AU$5,183,474 and AU$6,736,513 from the DHA and societal perspectives. The generalizability and transferability of results to other settings, populations, or brands of infant formula should be made with caution. Whenever possible, a conservative approach directing bias against PHF-W rather than its comparators was applied in the base case analysis. Assumptions were verified in one-way and probabilistic sensitivity analyses, which confirmed the robustness of the model. PHF-W appears to be cost-effective when compared to SF from the DHA perspective, dominant over SF from the other perspectives, and dominant over EHF-Whey from all perspectives, in the prevention of AD in 'at risk' infants not exclusively breastfed, in Australia.

Characterizing Longitudinal Patterns of Physical Activity in Mid-Adulthood Using Latent Class Analysis: Results From a Prospective Cohort Study

PubMed Central

Silverwood, Richard J.; Nitsch, Dorothea; Pierce, Mary; Kuh, Diana; Mishra, Gita D.

2011-01-01

The authors aimed to describe how longitudinal patterns of physical activity during mid-adulthood (ages 31–53 years) can be characterized using latent class analysis in a population-based birth cohort study, the Medical Research Council’s 1946 National Survey of Health and Development. Three different types of physical activity—walking, cycling, and leisure-time physical activity—were analyzed separately using self-reported data collected from questionnaires between 1977 and 1999; 3,847 study members were included in the analysis for one or more types of activity. Patterns of activity differed by sex, so stratified analyses were conducted. Two walking latent classes were identified representing low (52.8% of males in the cohort, 33.5% of females) and high (47.2%, 66.5%) levels of activity. Similar low (91.4%, 82.1%) and high (8.6%, 17.9%) classes were found for cycling, while 3 classes were identified for leisure-time physical activity: “low activity” (46.2%, 48.2%), “sports and leisure activity” (31.0%, 35.3%), and “gardening and do-it-yourself activities” (22.8%, 16.5%). The classes were reasonably or very well separated, with the exception of walking in females. Latent class analysis was found to be a useful tool for characterizing longitudinal patterns of physical activity, even when the measurement instrument differs slightly across ages, which added value in comparison with observed activity at a single age. PMID:22074812

Cost-benefit analysis of a Haemophilus influenzae type b meningitis prevention programme in The Philippines.

PubMed

Limcangco, M R; Armour, C L; Salole, E G; Taylor, S J

2001-01-01

Haemophilus influenzae type b (Hib) meningitis is associated with high mortality and serious sequelae in children under 5 years of age. Vaccines which can prevent this infection are available. To evaluate the costs and benefits of a 3-dose immunisation schedule in Manila, Philippines. Government and societal perspectives. A cost-benefit analysis based on a birth cohort of 100,000 children. The state of health of the cohort with and without a Hib immunisation programme was modelled over a 5-year period. A survey of medical records of patients with Hib in Manila provided data on the extent and cost of sequelae following infection. A 3-dose Hib vaccination programme given at ages 2, 3 and 4 months. The model predicted that vaccinating children against Hib meningitis would prevent 553 cases per year in a birth cohort of 100,000, at a cost of 56,200 Philippine pesos (PHP) [$US1,605; 1998 exchange rate] per case (base case assumptions of 90% vaccine efficacy rate, 95 per 100,000 Hib incidence rate, 85% vaccination coverage). Results from the cost-benefit analyses indicated that the saving to the government would be around PHP39 million ($US1.11 million), and the saving to society would be PHP255 million ($US7.28 million). There would be a positive economic benefit for the Philippine government and for the Filipino society if a Hib vaccination programme was introduced in Manila.

Luminal-like HER2-negative stage IA breast cancer: a multicenter retrospective study on long-term outcome with propensity score analysis

PubMed Central

De Angelis, Carmine; Di Maio, Massimo; Crispo, Anna; Giuliano, Mario; Schettini, Francesco; Bonotto, Marta; Gerratana, Lorenzo; Iacono, Donatella; Cinausero, Marika; Riccardi, Ferdinando; Ciancia, Giuseppe; De Laurentiis, Michelino; Puglisi, Fabio; De Placido, Sabino; Arpino, Grazia

2017-01-01

The benefit of adding chemotherapy (CT) to adjuvant hormone therapy (HT) in stage IA luminal-like HER2-negative breast cancer (BC) is unclear. We retrospectively evaluated predictive factors and clinical outcome of 1,222 patients from 4 oncologic centers. Three hundred and eighty patients received CT and HT (CT-cohort) and 842 received HT alone (HT-cohort). Disease-free survival (DFS) and overall survival (OS) were evaluated with univariate and multivariate analyses. We also applied the propensity score methodology. Compared with the HT-cohort, patients in the CT-cohort were more likely to be younger, have larger tumors of a higher histological grade that were Ki67-positive, and lower estrogen and progesterone receptor expression. At univariate analysis, a higher histological grade and Ki67 were significantly associated to a lower DFS. At multivariable analysis, only histological grade was predictive of DFS. The CT-cohort had a worse outcome than the HT-cohort in terms of DFS and OS, but differences disappeared when matched according to propensity score. In summary, patients with stage IA luminal-like BC had an excellent prognosis, however relapse and mortality were higher in the CT-cohort than in the HT-cohort. Longer use of adjuvant HT or other therapeutic strategies may be needed to improve outcome. PMID:29348868

Navigating complex lives: a longitudinal, comparative perspective on young people's trajectories.

PubMed

Wyn, Johanna; Andres, Lesley

2011-02-01

Drawing on a sociological analysis that brings the prevailing social and economic policies into the frame of this analysis, this article focuses on the relationship between the social conditions faced by young people in the 1990s and early 2000s, the opportunities and constraints that these conditions presented to them, and patterns of mental health. The article presents an analysis of selected data from two longitudinal cohort studies. One is the Paths on Life's Way cohort study by Andres, based in British Columbia, Canada, and the other is the Life-Patterns cohort by Wyn, based in Victoria, Australia. These cohort studies have tracked the lives of young people who entered the labour market in the early 1990s. The longitudinal analysis is based on the data available for 733 participants in the Canadian study in 2003, and 625 participants in the Australian study in 2004, which remains representative of the larger original samples. The data were collected through a mixed-method approach of surveys and interviews. As part of the study, education and employment policies in Australia and Canada during the 1990 s were also analysed. The data reveal that it took 14 years from the time of leaving secondary school for the majority of Australians and Canadians to find a degree of employment security. Young Australians had lower rates of marriage and fertility, and assessed their mental health as being worse than their Canadian peers. Education and labour market policies aimed to increase human capital to ensure global competitiveness and to increase the flexibility of labour for employers. Social policies matter. In both countries, the creation of higher levels of human capital through increasing young people's participation in education, combined with labour market policies that increased job uncertainty and labour market precariousness meant that young people found it difficult to achieve their goals of modest affluence and security. The policies had an impact on young people's marriage rates and fertility, particularly for the Australians. These social conditions also had the effect of increasing young people's assessments of their mental health as poor. Greater attention needs to be paid to the impact of social policies on areas that lie outside their immediate domain. Addressing young people's mental health requires an awareness of the inter-connections across policy areas, and the recognition that mental health is an outcome of social conditions. © 2011 Blackwell Publishing Asia Pty Ltd.

Stochastic models to demonstrate the effect of motivated testing on HIV incidence estimates using the serological testing algorithm for recent HIV seroconversion (STARHS).

PubMed

White, Edward W; Lumley, Thomas; Goodreau, Steven M; Goldbaum, Gary; Hawes, Stephen E

2010-12-01

To produce valid seroincidence estimates, the serological testing algorithm for recent HIV seroconversion (STARHS) assumes independence between infection and testing, which may be absent in clinical data. STARHS estimates are generally greater than cohort-based estimates of incidence from observable person-time and diagnosis dates. The authors constructed a series of partial stochastic models to examine whether testing motivated by suspicion of infection could bias STARHS. One thousand Monte Carlo simulations of 10,000 men who have sex with men were generated using parameters for HIV incidence and testing frequency from data from a clinical testing population in Seattle. In one set of simulations, infection and testing dates were independent. In another set, some intertest intervals were abbreviated to reflect the distribution of intervals between suspected HIV exposure and testing in a group of Seattle men who have sex with men recently diagnosed as having HIV. Both estimation methods were applied to the simulated datasets. Both cohort-based and STARHS incidence estimates were calculated using the simulated data and compared with previously calculated, empirical cohort-based and STARHS seroincidence estimates from the clinical testing population. Under simulated independence between infection and testing, cohort-based and STARHS incidence estimates resembled cohort estimates from the clinical dataset. Under simulated motivated testing, cohort-based estimates remained unchanged, but STARHS estimates were inflated similar to empirical STARHS estimates. Varying motivation parameters appreciably affected STARHS incidence estimates, but not cohort-based estimates. Cohort-based incidence estimates are robust against dependence between testing and acquisition of infection, whereas STARHS incidence estimates are not.

The effect of the introduction of a regional major trauma network on triage decisions made by a physician-staffed helicopter emergency medical service.

PubMed

Chesters, Adam; Fenton, Ronan

2015-12-01

A major trauma network (MTN) has been in place in the East of England, with a single hospital operating as the major trauma centre (MTC). The primary aim of this retrospective cohort study was to determine whether triage destination decisions with regard to trauma patients made by a helicopter-based doctor-paramedic team are affected by the introduction of a regional trauma network. In addition, we will describe and discuss the logistics of transfer of injured patients attended by the service. This is a retrospective database review that was carried out over two 12-month periods. The first period was before the introduction of an MTN, and the second was after its introduction. All patients who were conveyed to an MTC were identified. Nontrauma patients were excluded. The MTN trauma triage tool was retrospectively applied. A comparative analysis of the two cohorts was carried out. For the group of patients conveyed to the regional MTC, additional follow-up information was obtained. This included patient survival at 30 days and the final injury severity score for each patient. A total of 220 cases were identified in which a major trauma patient was conveyed to an MTC. There were 94 cases in the year before the introduction of the MTN (cohort 1) and 124 in the year during which the MTN was active (cohort 2). There was no significant difference in the number of patients conveyed to each MTC between cohort 1 and cohort 2. The trauma triage tool status was 'positive' in 52.1% of cases in cohort 1 and 55.6% of cases in cohort 2 (P=0.60). Advice of the consultant on call was more commonly used for patients in cohort 2 than for those in cohort 1 (66.9 vs. 40.6%; P<0. 01). The introduction of a regional MTN has not significantly affected the triage decisions made by our physician-paramedic teams.

External validity of two nomograms for predicting distant brain failure after radiosurgery for brain metastases in a bi-institutional independent patient cohort.

PubMed

Prabhu, Roshan S; Press, Robert H; Boselli, Danielle M; Miller, Katherine R; Lankford, Scott P; McCammon, Robert J; Moeller, Benjamin J; Heinzerling, John H; Fasola, Carolina E; Patel, Kirtesh R; Asher, Anthony L; Sumrall, Ashley L; Curran, Walter J; Shu, Hui-Kuo G; Burri, Stuart H

2018-03-01

Patients treated with stereotactic radiosurgery (SRS) for brain metastases (BM) are at increased risk of distant brain failure (DBF). Two nomograms have been recently published to predict individualized risk of DBF after SRS. The goal of this study was to assess the external validity of these nomograms in an independent patient cohort. The records of consecutive patients with BM treated with SRS at Levine Cancer Institute and Emory University between 2005 and 2013 were reviewed. Three validation cohorts were generated based on the specific nomogram or recursive partitioning analysis (RPA) entry criteria: Wake Forest nomogram (n = 281), Canadian nomogram (n = 282), and Canadian RPA (n = 303) validation cohorts. Freedom from DBF at 1-year in the Wake Forest study was 30% compared with 50% in the validation cohort. The validation c-index for both the 6-month and 9-month freedom from DBF Wake Forest nomograms was 0.55, indicating poor discrimination ability, and the goodness-of-fit test for both nomograms was highly significant (p < 0.001), indicating poor calibration. The 1-year actuarial DBF in the Canadian nomogram study was 43.9% compared with 50.9% in the validation cohort. The validation c-index for the Canadian 1-year DBF nomogram was 0.56, and the goodness-of-fit test was also highly significant (p < 0.001). The validation accuracy and c-index of the Canadian RPA classification was 53% and 0.61, respectively. The Wake Forest and Canadian nomograms for predicting risk of DBF after SRS were found to have limited predictive ability in an independent bi-institutional validation cohort. These results reinforce the importance of validating predictive models in independent patient cohorts.

Evidence-based cancer prevention recommendations for Japanese.

PubMed

Sasazuki, S; Inoue, M; Shimazu, T; Wakai, K; Naito, M; Nagata, C; Tanaka, K; Tsuji, I; Sugawara, Y; Mizoue, T; Matsuo, K; Ito, H; Tamakoshi, A; Sawada, N; Nakayama, T; Kitamura, Y; Sadakane, A; Tsugane, S

2018-06-01

A comprehensive evidence-based cancer prevention recommendation for Japanese was developed. We evaluated the magnitude of the associations of lifestyle factors and infection with cancer through a systematic review of the literature, meta-analysis of published data, and pooled analysis of cohort studies in Japan. Then, we judged the strength of evidence based on the consistency of the associations between exposure and cancer and biological plausibility. Important factors were extracted and summarized as an evidence-based, current cancer prevention recommendation: 'Cancer Prevention Recommendation for Japanese'. The recommendation addresses six important domains related to exposure and cancer, including smoking, alcohol drinking, diet, physical activity, body weight and infection. The next step should focus on the development of effective behavior modification programs and their implementation and dissemination.

Low-Carbohydrate-Diet Score and its Association with the Risk of Diabetes: A Systematic Review and Meta-Analysis of Cohort Studies.

PubMed

Namazi, Nazli; Larijani, Bagher; Azadbakht, Leila

2017-08-01

The association between a low-carbohydrate diet (LCD) score and the risk of diabetes mellitus (DM) is contradictory. This study is a systemic review of cohort studies that have focused on the association between the LCD score and DM. We searched PubMed/Medline, Scopus, Embase, ISI Web of Science, and Google Scholar for papers published through January 2017 with no language restrictions. Cohort studies that reported relative risks (RRs) with 95% confidence intervals (CI) for DM were included. Finally, 4 studies were considered for our meta-analysis. The total number of participants ranged from 479 to 85 059. Among 4 cohort studies, 8 081 cases with DM were observed over follow-up durations ranging from 3.6 to 20 years. A marginal significant association was observed between the highest LCD score and the risk of DM (RR=1.17; 95% CI: 0.9, 1.51). Moreover, the RRs for studies with energy adjustments showed a significant association (RR: 1.32; 95% CI: 1.17, 1.49; I 2 : 0%). Based on our findings, study qualities score of less or equal to 7 had a significant influence on the pooled effect size (RR=1.31, 95%CI: 1.15, 1.49; I 2 : 0%), whereas the overall RR in the studies with quality score more than 7 was 1.09 (95% CI: 0.73, 1.63). In conclusion, we have found that the highest LCD score was marginally associated with the risk of DM. However, more prospective cohort studies are needed to clarify the effects of the LCD score on the risk of DM. © Georg Thieme Verlag KG Stuttgart · New York.

Risk of Vertebral Fracture in Patients Diagnosed with a Depressive Disorder: A Nationwide Population-Based Cohort Study

PubMed Central

Lee, Shyh-Chyang; Hu, Li-Yu; Huang, Min-Wei; Shen, Cheng-Che; Huang, Wei-Lun; Lu, Ti; Hsu, Chiao-Lin; Pan, Chih-Chuan

2017-01-01

OBJECTIVE: Previous studies have reported that depression may play a crucial role in the occurrence of vertebral fractures. However, a clear correlation between depressive disorders and osteoporotic fractures has not been established. We explored the association between depressive disorders and subsequent new-onset vertebral fractures. Additionally, we aimed to identify the potential risk factors for vertebral fracture in patients with a depressive disorder. METHODS: We studied patients listed in the Taiwan National Health Insurance Research Database who were diagnosed with a depressive disorder by a psychiatrist. The comparison cohort consisted of age- and sex-matched patients without a depressive disorder. The incidence rate and hazard ratios of subsequent vertebral fracture were evaluated. We used Cox regression analysis to evaluate the risk of vertebral fracture among patients with a depressive disorder. RESULTS: The total number of patients with and without a depressive disorder was 44,812. The incidence risk ratio (IRR) between these 2 cohorts indicated that depressive disorder patients had a higher risk of developing a subsequent vertebral fracture (IRR=1.41, 95% confidence interval [CI]=1.26–1.57, p<0.001). In the multivariate analysis, the depressive disorder cohort showed a higher risk of vertebral fracture than the comparison cohort (adjusted hazard ratio=1.24, 95% CI=1.11–1.38, p<0.001). Being older than 50 years, having a lower monthly income, and having hypertension, diabetes mellitus, cerebrovascular disease, chronic obstructive pulmonary disease, autoimmune disease, or osteoporosis were considered predictive factors for vertebral fracture in patients with depressive disorders. CONCLUSIONS: Depressive disorders may increase the risk of a subsequent new-onset vertebral fracture. PMID:28226032

Tenofovir in second-line ART in Zambia and South Africa: Collaborative analysis of cohort studies

PubMed Central

Wandeler, Gilles; Keiser, Olivia; Mulenga, Lloyd; Hoffmann, Christopher J; Wood, Robin; Chaweza, Thom; Brennan, Alana; Prozesky, Hans; Garone, Daniela; Giddy, Janet; Chimbetete, Cleophas; Boulle, Andrew; Egger, Matthias

2012-01-01

Objectives Tenofovir (TDF) is increasingly used in second-line antiretroviral treatment (ART) in sub-Saharan Africa. We compared outcomes of second-line ART containing and not containing TDF in cohort studies from Zambia and the Republic of South Africa (RSA). Methods Patients aged ≥ 16 years starting protease inhibitor-based second-line ART in Zambia (1 cohort) and RSA (5 cohorts) were included. We compared mortality, immunological failure (all cohorts) and virological failure (RSA only) between patients receiving and not receiving TDF. Competing risk models and Cox models adjusted for age, sex, CD4 count, time on first-line ART and calendar year were used to analyse mortality and treatment failure, respectively. Hazard ratios (HRs) were combined in fixed-effects meta-analysis. Findings 1,687 patients from Zambia and 1,556 patients from RSA, including 1,350 (80.0%) and 206 (13.2%) patients starting TDF, were followed over 4,471 person-years. Patients on TDF were more likely to have started second-line ART in recent years, and had slightly higher baseline CD4 counts than patients not on TDF. Overall 127 patients died, 532 were lost to follow-up and 240 patients developed immunological failure. In RSA 94 patients had virologic failure. Combined HRs comparing tenofovir with other regimens were 0.60 (95% CI 0.41–0.87) for immunologic failure and 0.63 (0.38–1.05) for mortality. The HR for virologic failure in RSA was 0.28 (0.09–0.90). Conclusions In this observational study patients on TDF-containing second-line ART were less likely to develop treatment failure than patients on other regimens. TDF seems to be an effective component of second-line ART in southern Africa. PMID:22743595

Genome-wide analysis of epistasis in body mass index using multiple human populations.

PubMed

Wei, Wen-Hua; Hemani, Gib; Gyenesei, Attila; Vitart, Veronique; Navarro, Pau; Hayward, Caroline; Cabrera, Claudia P; Huffman, Jennifer E; Knott, Sara A; Hicks, Andrew A; Rudan, Igor; Pramstaller, Peter P; Wild, Sarah H; Wilson, James F; Campbell, Harry; Hastie, Nicholas D; Wright, Alan F; Haley, Chris S

2012-08-01

We surveyed gene-gene interactions (epistasis) in human body mass index (BMI) in four European populations (n<1200) via exhaustive pair-wise genome scans where interactions were computed as F ratios by testing a linear regression model fitting two single-nucleotide polymorphisms (SNPs) with interactions against the one without. Before the association tests, BMI was corrected for sex and age, normalised and adjusted for relatedness. Neither single SNPs nor SNP interactions were genome-wide significant in either cohort based on the consensus threshold (P=5.0E-08) and a Bonferroni corrected threshold (P=1.1E-12), respectively. Next we compared sub genome-wide significant SNP interactions (P<5.0E-08) across cohorts to identify common epistatic signals, where SNPs were annotated to genes to test for gene ontology (GO) enrichment. Among the epistatic genes contributing to the commonly enriched GO terms, 19 were shared across study cohorts of which 15 are previously published genome-wide association loci, including CDH13 (cadherin 13) associated with height and SORCS2 (sortilin-related VPS10 domain containing receptor 2) associated with circulating insulin-like growth factor 1 and binding protein 3. Interactions between the 19 shared epistatic genes and those involving BMI candidate loci (P<5.0E-08) were tested across cohorts and found eight replicated at the SNP level (P<0.05) in at least one cohort, which were further tested and showed limited replication in a separate European population (n>5000). We conclude that genome-wide analysis of epistasis in multiple populations is an effective approach to provide new insights into the genetic regulation of BMI but requires additional efforts to confirm the findings.

Risk of Vertebral Fracture in Patients Diagnosed with a Depressive Disorder: A Nationwide Population-Based Cohort Study.

PubMed

Lee, Shyh-Chyang; Hu, Li-Yu; Huang, Min-Wei; Shen, Cheng-Che; Huang, Wei-Lun; Lu, Ti; Hsu, Chiao-Lin; Pan, Chih-Chuan

2017-01-01

Previous studies have reported that depression may play a crucial role in the occurrence of vertebral fractures. However, a clear correlation between depressive disorders and osteoporotic fractures has not been established. We explored the association between depressive disorders and subsequent new-onset vertebral fractures. Additionally, we aimed to identify the potential risk factors for vertebral fracture in patients with a depressive disorder. We studied patients listed in the Taiwan National Health Insurance Research Database who were diagnosed with a depressive disorder by a psychiatrist. The comparison cohort consisted of age- and sex-matched patients without a depressive disorder. The incidence rate and hazard ratios of subsequent vertebral fracture were evaluated. We used Cox regression analysis to evaluate the risk of vertebral fracture among patients with a depressive disorder. The total number of patients with and without a depressive disorder was 44,812. The incidence risk ratio (IRR) between these 2 cohorts indicated that depressive disorder patients had a higher risk of developing a subsequent vertebral fracture (IRR=1.41, 95% confidence interval [CI]=1.26-1.57, p<0.001). In the multivariate analysis, the depressive disorder cohort showed a higher risk of vertebral fracture than the comparison cohort (adjusted hazard ratio=1.24, 95% CI=1.11-1.38, p<0.001). Being older than 50 years, having a lower monthly income, and having hypertension, diabetes mellitus, cerebrovascular disease, chronic obstructive pulmonary disease, autoimmune disease, or osteoporosis were considered predictive factors for vertebral fracture in patients with depressive disorders. Depressive disorders may increase the risk of a subsequent new-onset vertebral fracture.

DNA methylation array analysis identifies breast cancer associated RPTOR, MGRN1 and RAPSN hypomethylation in peripheral blood DNA.

PubMed

Tang, Qiuqiong; Holland-Letz, Tim; Slynko, Alla; Cuk, Katarina; Marme, Frederik; Schott, Sarah; Heil, Jörg; Qu, Bin; Golatta, Michael; Bewerunge-Hudler, Melanie; Sutter, Christian; Surowy, Harald; Wappenschmidt, Barbara; Schmutzler, Rita; Hoth, Markus; Bugert, Peter; Bartram, Claus R; Sohn, Christof; Schneeweiss, Andreas; Yang, Rongxi; Burwinkel, Barbara

2016-09-27

DNA methylation changes in peripheral blood DNA have been shown to be associated with solid tumors. We sought to identify methylation alterations in whole blood DNA that are associated with breast cancer (BC). Epigenome-wide DNA methylation profiling on blood DNA from BC cases and healthy controls was performed by applying Infinium HumanMethylation450K BeadChips. Promising CpG sites were selected and validated in three independent larger sample cohorts via MassARRAY EpiTyper assays. CpG sites located in three genes (cg06418238 in RPTOR, cg00736299 in MGRN1 and cg27466532 in RAPSN), which showed significant hypomethylation in BC patients compared to healthy controls in the discovery cohort (p < 1.00 x 10-6) were selected and successfully validated in three independent cohorts (validation I, n =211; validation II, n=378; validation III, n=520). The observed methylation differences are likely not cell-type specific, as the differences were only seen in whole blood, but not in specific sub cell-types of leucocytes. Moreover, we observed in quartile analysis that women in the lower methylation quartiles of these three loci had higher ORs than women in the higher quartiles. The combined AUC of three loci was 0.79 (95%CI 0.73-0.85) in validation cohort I, and was 0.60 (95%CI 0.54-0.66) and 0.62 (95%CI 0.57-0.67) in validation cohort II and III, respectively. Our study suggests that hypomethylation of CpG sites in RPTOR, MGRN1 and RAPSN in blood is associated with BC and might serve as blood-based marker supplements for BC if these could be verified in prospective studies.

Impact of Remote Monitoring on Long-Term Prognosis in Heart Failure Patients in a Real-World Cohort: Results From All-Comers COMMIT-HF Trial.

PubMed

Kurek, Anna; Tajstra, Mateusz; Gadula-Gacek, Elzbieta; Buchta, Piotr; Skrzypek, Michal; Pyka, Lukasz; Wasiak, Michal; Swietlinska, Malgorzata; Hawranek, Michal; Polonski, Lech; Gasior, Mariusz; Kosiuk, Jedrzej

2017-04-01

Randomized controlled trials demonstrate that remote monitoring (RM) of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy devices (CRT-Ds) may improve quality of care and prognosis in heart failure (HF) patients. However, the impact of RM on long-term mortality in a real-world cohort is still not well examined. This study was designed as a matched cohort study based on the COMMIT-HF trial--a single-center, ongoing prospective observational registry (NCT02536443). Complete patient demographics, medical history, in-hospital results, hospitalizations, and mortality data were collected based on institutional registries and healthcare providers' records. Patients were divided into 2 groups based on RM presence and matched by means of propensity scores according to clinical characteristics. The primary endpoint of this study was the long-term all-cause mortality. Out of 1,429 consecutive patients, 822 patients with a first implantation of an ICD/CRT-D were included in the analysis. The final matched study population contained 574 patients in RM and in a control group. Although demographic and echocardiographic parameters as well as pharmacological treatments were similar in both groups, a significantly lower 1-year mortality was detected in the RM group (2.1% vs. 11.5%, P < 0.0001). This was also maintained during a 3-year follow-up (4.9% vs. 22.3%, P < 0.0001). Multivariate analysis showed that RM was associated with an improved prognosis (hazard ratio 0.187, 95% confidence interval 0.075-0.467, P = 0.0003). RM of HF patients with ICDs/CRT-Ds significantly reduced long-term mortality in a real-world clinical condition. © 2017 Wiley Periodicals, Inc.

Cystatin C versus Creatinine in Determining Risk Based on Kidney Function

PubMed Central

Shlipak, Michael G.; Matsushita, Kunihiro; Ärnlöv, Johan; Inker, Lesley A.; Katz, Ronit; Polkinghorne, Kevan R.; Rothenbacher, Dietrich; Sarnak, Mark J.; Astor, Brad C.; Coresh, Josef; Levey, Andrew S.; Gansevoort, Ron T.

2014-01-01

BACKGROUND Adding the measurement of cystatin C to that of serum creatinine to determine the estimated glomerular filtration rate (eGFR) improves accuracy, but the effect on detection, staging, and risk classification of chronic kidney disease across diverse populations has not been determined. METHODS We performed a meta-analysis of 11 general-population studies (with 90,750 participants) and 5 studies of cohorts with chronic kidney disease (2960 participants) for whom standardized measurements of serum creatinine and cystatin C were available. We compared the association of the eGFR, as calculated by the measurement of creatinine or cystatin C alone or in combination with creatinine, with the rates of death (13,202 deaths in 15 cohorts), death from cardiovascular causes (3471 in 12 cohorts), and end-stage renal disease (1654 cases in 7 cohorts) and assessed improvement in reclassification with the use of cystatin C. RESULTS In the general-population cohorts, the prevalence of an eGFR of less than 60 ml per minute per 1.73 m2 of body-surface area was higher with the cystatin C–based eGFR than with the creatinine-based eGFR (13.7% vs. 9.7%). Across all eGFR categories, the reclassification of the eGFR to a higher value with the measurement of cystatin C, as compared with creatinine, was associated with a reduced risk of all three study outcomes, and reclassification to a lower eGFR was associated with an increased risk. The net reclassification improvement with the measurement of cystatin C, as compared with creatinine, was 0.23 (95% confidence interval [CI], 0.18 to 0.28) for death and 0.10 (95% CI, 0.00 to 0.21) for end-stage renal disease. Results were generally similar for the five cohorts with chronic kidney disease and when both creatinine and cystatin C were used to calculate the eGFR. CONCLUSIONS The use of cystatin C alone or in combination with creatinine strengthens the association between the eGFR and the risks of death and end-stage renal disease across diverse populations. (Funded by the National Kidney Foundation and others.) PMID:24004120

Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling.

PubMed

Kochunov, Peter; Jahanshad, Neda; Sprooten, Emma; Nichols, Thomas E; Mandl, René C; Almasy, Laura; Booth, Tom; Brouwer, Rachel M; Curran, Joanne E; de Zubicaray, Greig I; Dimitrova, Rali; Duggirala, Ravi; Fox, Peter T; Hong, L Elliot; Landman, Bennett A; Lemaitre, Hervé; Lopez, Lorna M; Martin, Nicholas G; McMahon, Katie L; Mitchell, Braxton D; Olvera, Rene L; Peterson, Charles P; Starr, John M; Sussmann, Jessika E; Toga, Arthur W; Wardlaw, Joanna M; Wright, Margaret J; Wright, Susan N; Bastin, Mark E; McIntosh, Andrew M; Boomsma, Dorret I; Kahn, René S; den Braber, Anouk; de Geus, Eco J C; Deary, Ian J; Hulshoff Pol, Hilleke E; Williamson, Douglas E; Blangero, John; van 't Ent, Dennis; Thompson, Paul M; Glahn, David C

2014-07-15

Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large "mega-family". We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability. Copyright © 2014 Elsevier Inc. All rights reserved.

Estimation of fat-free mass in Asian neonates using bioelectrical impedance analysis

PubMed Central

Tint, Mya-Thway; Ward, Leigh C; Soh, Shu E; Aris, Izzuddin M; Chinnadurai, Amutha; Saw, Seang Mei; Gluckman, Peter D; Godfrey, Keith M; Chong, Yap-Seng; Kramer, Michael S; Yap, Fabian; Lingwood, Barbara; Lee, Yung Seng

2016-01-01

The aims of this study were to develop and validate a prediction equation of fat-free mass (FFM) based on bioelectrical impedance analysis (BIA) and anthropometry using air displacement plethysmography (ADP) as a reference in Asian neonates and to test the applicability of the prediction equations in independent Western cohort. A total of 173 neonates at birth and 140 at week-2 of age were included. Multiple linear regression analysis was performed to develop the prediction equations in a two-third randomly selected subset and validated on the remaining one-third subset at each time point and in an independent Queensland cohort. FFM measured by ADP was the dependent variable and anthropometric measures, sex and impedance quotient (L2/R50) were independent variables in the model. Accuracy of prediction equations were assessed using intra-class correlation and Bland-Altman analyses. L2/R50 was the significant predictor of FFM at week-2 but not at birth. Compared to the model using weight, sex and length, including L2/R50 slightly improved the prediction with a bias of 0.01kg with 2SD limits of agreement (LOA) (0.18, −0.20). Prediction explained 88.9% of variation but not beyond that of anthropometry. Applying these equations to Queensland cohort provided similar performance at the appropriate age. However, when the Queensland equations were applied to our cohort, the bias increased slightly but with similar LOA. BIA appears to have limited use in predicting FFM in the first few weeks of life compared to simple anthropometry in Asian populations. There is a need for population and age appropriate FFM prediction equations. PMID:26856420

Estimation of fat-free mass in Asian neonates using bioelectrical impedance analysis.

PubMed

Tint, Mya-Thway; Ward, Leigh C; Soh, Shu E; Aris, Izzuddin M; Chinnadurai, Amutha; Saw, Seang Mei; Gluckman, Peter D; Godfrey, Keith M; Chong, Yap-Seng; Kramer, Michael S; Yap, Fabian; Lingwood, Barbara; Lee, Yung Seng

2016-03-28

The aims of this study were to develop and validate a prediction equation of fat-free mass (FFM) based on bioelectrical impedance analysis (BIA) and anthropometry using air-displacement plethysmography (ADP) as a reference in Asian neonates and to test the applicability of the prediction equations in an independent Western cohort. A total of 173 neonates at birth and 140 at two weeks of age were included. Multiple linear regression analysis was performed to develop the prediction equations in a two-third randomly selected subset and validated on the remaining one-third subset at each time point and in an independent Queensland cohort. FFM measured by ADP was the dependent variable, and anthropometric measures, sex and impedance quotient (L2/R50) were independent variables in the model. Accuracy of prediction equations was assessed using intra-class correlation and Bland-Altman analyses. L2/R50 was the significant predictor of FFM at week two but not at birth. Compared with the model using weight, sex and length, including L2/R50 slightly improved the prediction with a bias of 0·01 kg with 2 sd limits of agreement (LOA) (0·18, -0·20). Prediction explained 88·9 % of variation but not beyond that of anthropometry. Applying these equations to the Queensland cohort provided similar performance at the appropriate age. However, when the Queensland equations were applied to our cohort, the bias increased slightly but with similar LOA. BIA appears to have limited use in predicting FFM in the first few weeks of life compared with simple anthropometry in Asian populations. There is a need for population- and age-appropriate FFM prediction equations.

Alcohol-related morbidity and mortality within siblings.

PubMed

Søndergaard, Grethe; Osler, Merete; Andersen, Anne-Marie Nybo; Andersen, Per Kragh; Dalton, Susanne Oksbjerg; Mortensen, Laust H

2015-03-01

To estimate the association between educational status and alcohol-related somatic and non-somatic morbidity and mortality among full siblings in comparison with non-related individuals. Cohort study. Denmark. Approximately 1.4 million full siblings born in Denmark between 1950 and 1979 were followed from age 28-58 years or censoring due to alcohol-related hospitalization and mortality. Cox regression analyses were used to estimate associations of educational status with alcohol-related outcomes. Results from cohort analyses based on non-related individuals and inter-sibling analyses were compared. A lower educational status was associated with a higher rate of alcohol-related outcomes, especially among the youngest (aged 28-37 years) and individuals born 1970-79. Compared with the cohort analyses, the associations attenuated slightly in the inter-sibling analysis. For example, in the cohort analysis, females with a basic school education born 1970-79 had an increased rate of alcohol-related non-somatic morbidity and mortality [hazard rate ratio (HR) = 4.05, 95% confidence interval (CI) = 3.27-5.02] compared to those with a vocational education. In the inter-sibling analysis, the HR attenuated (HR = 2.66, 95% CI = 1.95-3.63). For alcohol-related somatic outcomes the corresponding figures were HR = 3.47 (95% CI = 2.63-4.58) and HR = 3.36 (95% CI = 2.10-5.38), respectively. In general, the associations were stronger among females than males (aged 28-37) in the analyses of alcohol-related non-somatic outcomes. Health conditions earlier in life explained only a minor part of the associations. The association between educational status and alcohol-related somatic and non-somatic morbidity and mortality is only driven by familial factors to a small degree. © 2014 Society for the Study of Addiction.

Development of the Ovarian Cancer Cohort Consortium: Risk Factor Associations by Heterogeneity of Disease

DTIC Science & Technology

2015-10-01

K05CA154337 from the National Cancer Institute (NCI) and Office of Dietary Supplements (VITAL). R01 CA39742 (Iowa Women’s Health Study). NIH/NCI UM1...did not collect information on a specific risk factor were excluded from the analysis of that factor ( Supplemental Table 1), leading to different... Supplemental Table 3. Associationsa of risk factors with ovarian cancer subtypes based on meta-analysis pooling the results of individual studies

Efficient genotype compression and analysis of large genetic variation datasets

PubMed Central

Layer, Ryan M.; Kindlon, Neil; Karczewski, Konrad J.; Quinlan, Aaron R.

2015-01-01

Genotype Query Tools (GQT) is a new indexing strategy that expedites analyses of genome variation datasets in VCF format based on sample genotypes, phenotypes and relationships. GQT’s compressed genotype index minimizes decompression for analysis, and performance relative to existing methods improves with cohort size. We show substantial (up to 443 fold) performance gains over existing methods and demonstrate GQT’s utility for exploring massive datasets involving thousands to millions of genomes. PMID:26550772

Endotoxin exposure and lung cancer risk: a systematic review and meta-analysis of the published literature on agriculture and cotton textile workers.

PubMed

Lenters, Virissa; Basinas, Ioannis; Beane-Freeman, Laura; Boffetta, Paolo; Checkoway, Harvey; Coggon, David; Portengen, Lützen; Sim, Malcolm; Wouters, Inge M; Heederik, Dick; Vermeulen, Roel

2010-04-01

To examine the association between exposure to endotoxins and lung cancer risk by conducting a systematic review and meta-analysis of epidemiologic studies of workers in the cotton textile and agricultural industries; industries known for high exposure levels of endotoxins. Risk estimates were extracted from studies published before 2009 that met predefined quality criteria, including 8 cohort, 1 case-cohort, and 2 case-control studies of cotton textile industry workers, and 15 cohort and 2 case-control studies of agricultural workers. Summary risk estimates were calculated using random effects meta-analyses. Potential sources of heterogeneity were explored through subgroup analyses. The summary risk of lung cancer was 0.72 (95% CI, 0.57-0.90) for textile workers and 0.62 (0.52-0.75) for agricultural workers. The relative risk of lung cancer was below 1.0 for most subgroups defined according to sex, study design, outcome, smoking adjustment, and geographic area. Two studies provided quantitative estimates of endotoxin exposure and both studies tended to support a dose-dependent protective effect of endotoxins on lung cancer risk. Despite several limitations, this meta-analysis based on high-quality studies adds weight to the hypothesis that occupational exposure to endotoxin in cotton textile production and agriculture is protective against lung cancer.

Whole grain intake, determined by dietary records and plasma alkylresorcinol concentrations, is low among pregnant women in Singapore.

PubMed

Ross, Alastair B; Colega, Marjorelee T; Lim, Ai Lin; Silva-Zolezzi, Irma; Macé, Katherine; Saw, Seang Mei; Kwek, Kenneth; Gluckman, Peter; Godfrey, Keith M; Chong, Yap-Seng; Chong, Mary F F

2015-01-01

To quantify whole grain intake in pregnant women in Singapore in order to provide the first detailed analysis of whole grain intake in an Asian country and in pregnant women. Analysis of 24-h diet recalls in a cross-sectional cohort study and analysis of a biomarker of whole grain intake (plasma alkylresorcinols) in a subset of subjects. The Growing Up in Singapore Towards healthy Outcomes-mother offspring cohort study based in Singapore. 998 pregnant mothers with complete 24-h recalls taken during their 26-28th week of gestation. Plasma samples from a randomly select subset of 100 subjects were analysed for plasma alkylresorcinols. Median (IQR) whole grain intake for the cohort and the 30% who reported eating whole grains were 0 (IQR 0, 9) and 23.6 (IQR 14.6, 44.2) g/day respectively. Plasma alkylresorcinol concentrations were very low [median (IQR)=9 (3, 15) nmol/L], suggesting low intake of whole grain wheat in this population. Plasma alkylresorcinols were correlated with whole grain wheat intake (Spearman's r=0.35; p<0.01). Whole grain intake among pregnant mothers in Singapore was well below the 2-3 (60-95 g) servings of whole grains per day recommended by the Singapore Health Promotion Board. Efforts to increase whole grain intake should be supported to encourage people to choose whole grains over refined grains in their diet.

Improving accuracy and power with transfer learning using a meta-analytic database.

PubMed

Schwartz, Yannick; Varoquaux, Gaël; Pallier, Christophe; Pinel, Philippe; Poline, Jean-Baptiste; Thirion, Bertrand

2012-01-01

Typical cohorts in brain imaging studies are not large enough for systematic testing of all the information contained in the images. To build testable working hypotheses, investigators thus rely on analysis of previous work, sometimes formalized in a so-called meta-analysis. In brain imaging, this approach underlies the specification of regions of interest (ROIs) that are usually selected on the basis of the coordinates of previously detected effects. In this paper, we propose to use a database of images, rather than coordinates, and frame the problem as transfer learning: learning a discriminant model on a reference task to apply it to a different but related new task. To facilitate statistical analysis of small cohorts, we use a sparse discriminant model that selects predictive voxels on the reference task and thus provides a principled procedure to define ROIs. The benefits of our approach are twofold. First it uses the reference database for prediction, i.e., to provide potential biomarkers in a clinical setting. Second it increases statistical power on the new task. We demonstrate on a set of 18 pairs of functional MRI experimental conditions that our approach gives good prediction. In addition, on a specific transfer situation involving different scanners at different locations, we show that voxel selection based on transfer learning leads to higher detection power on small cohorts.

The Basilar Artery on Computed Tomography Angiography Prognostic Score for Basilar Artery Occlusion.

PubMed

Alemseged, Fana; Shah, Darshan G; Diomedi, Marina; Sallustio, Fabrizio; Bivard, Andrew; Sharma, Gagan; Mitchell, Peter J; Dowling, Richard J; Bush, Steven; Yan, Bernard; Caltagirone, Carlo; Floris, Roberto; Parsons, Mark W; Levi, Christopher R; Davis, Stephen M; Campbell, Bruce C V

2017-03-01

Basilar artery occlusion is associated with high risk of disability and mortality. This study aimed to assess the prognostic value of a new radiological score: the Basilar Artery on Computed Tomography Angiography (BATMAN) score. A retrospective analysis of consecutive stroke patients with basilar artery occlusion diagnosed on computed tomographic angiography was performed. BATMAN score is a 10-point computed tomographic angiography-based grading system which incorporates thrombus burden and the presence of collaterals. Reliability was assessed with intraclass coefficient correlation. Good outcome was defined as modified Rankin Scale score of ≤3 at 3 months and successful reperfusion as thrombolysis in cerebral infarction 2b-3. BATMAN score was externally validated and compared with the Posterior Circulation Collateral score. The derivation cohort included 83 patients with 41 in the validation cohort. In receiver operating characteristic (ROC) analysis, BATMAN score had an area under receiver operating characteristic curve of 0.81 (95% confidence interval [CI], 0.7-0.9) in derivation cohort and an area under receiver operating characteristic curve of 0.74 (95% CI, 0.6-0.9) in validation cohort. In logistic regression adjusted for age and clinical severity, BATMAN score of <7 was associated with poor outcome in derivation cohort (odds ratio, 5.5; 95% CI, 1.4-21; P =0.01), in validation cohort (odds ratio, 6.9; 95% CI, 1.4-33; P =0.01), and in endovascular patients, after adjustment for recanalization and time to treatment (odds ratio, 4.8; 95% CI, 1.2-18; P =0.01). BATMAN score of <7 was not associated with recanalization. Interrater agreement was substantial (intraclass coefficient correlation, 0.85; 95% CI, 0.8-0.9). BATMAN score had greater accuracy compared with Posterior Circulation Collateral score ( P =0.04). The addition of collateral quality to clot burden in BATMAN score seems to improve prognostic accuracy in basilar artery occlusion patients. © 2017 American Heart Association, Inc.

Risk of radiation-induced malignancy with heterotopic ossification prophylaxis: a case-control analysis.

PubMed

Sheybani, Arshin; TenNapel, Mindi J; Lack, William D; Clerkin, Patrick; Hyer, Daniel E; Sun, Wenqing; Jacobson, Geraldine M

2014-07-01

To determine the risk of radiation-induced malignancy after prophylactic treatment for heterotopic ossification (HO). A matched case-control study was conducted within a population-based cohort of 3489 patients treated either for acetabular fractures with acetabular open reduction internal fixation or who underwent total hip arthroplasty from 1990 to 2009. Record-linkage techniques identified patients who were diagnosed with a malignancy from our state health registry. Patients with a prior history of malignancy were excluded from the cohort. For each documented case of cancer, 2 controls were selected by stratified random sampling from the cohort that did not develop a malignancy. Matching factors were sex, age at time of hip treatment, and duration of follow-up. A total of 243 patients were diagnosed with a malignancy after hip treatment. Five patients were excluded owing to inadequate follow-up time in the corresponding control cohort. A cohort of 238 cases (control, 476 patients) was included. Mean follow-up was 10 years, 12 years in the control group. In the cancer cohort, 4% of patients had radiation therapy (RT), compared with 7% in the control group. Of the 9 patients diagnosed with cancer after RT, none occurred within the field. The mean latency period was 5.9 years in the patients who received RT and 6.6 years in the patients who did not. Median (range) age at time of cancer diagnosis in patients who received RT was 62 (43-75) years, compared with 70 (32-92) years in the non-RT patients. An ad hoc analysis was subsequently performed in all 2749 patients who were not matched and found neither an increased incidence of malignancy nor a difference in distribution of type of malignancy. We were unable to demonstrate an increased risk of malignancy in patients who were treated with RT for HO prophylaxis compared with those who were not. Copyright © 2014 Elsevier Inc. All rights reserved.

Establishing a birth cohort to investigate the course and aetiology of asthma and allergies across three generations - rationale, design, and methods of the ACROSSOLAR study.

PubMed

Weinmann, Tobias; Gerlich, Jessica; Heinrich, Sabine; Nowak, Dennis; Gerdes, Jennifer; Schlichtiger, Jenny; von Mutius, Erika; Schaub, Bianca; Vogelberg, Christian; Roller, Diana; Radon, Katja

2015-12-04

Atopic diseases are a major burden of disease on a global scale. Regarding their aetiology, the early years of life are assumed to play a crucial role. In addition, there is growing evidence that elucidating the impact of cross-generational effects and epigenetic mechanisms such as DNA methylation can substantially widen the scientific knowledge of the occurrence and progression of these diseases. We are thus aiming at following the course of asthma, allergies, and potential risk factors for their occurrence across three generations by establishing a birth cohort in the offspring of an existing population-based cohort. 2051 young adults who have been recruited in 1995 for Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC) and who have subsequently been followed-up by the Study on Occupational Allergy Risks (SOLAR) are asked bi-annually since 2009 if they conceived a child in the meantime. If parenthood is reported, parents are invited to enrol along with their children in the ACROSSOLAR cohort. Participation involves completing a questionnaire assessing general and health-related information about the course of the pregnancy and the first year of life of their children. Subsequently, the children are followed up until primary school age when asthma and allergies can be diagnosed reliably. In addition, DNA for epigenetic analysis will be collected and analysed. Longitudinal data analysis techniques will then be used to assess potential associations between early-life exposures and onset of childhood asthma and allergies taking into account epigenetics. Birth cohorts are especially suited to elucidate the impact of genetic predisposition, epigenetics, exposures during the first years of life, and gene-environment interactions on the occurrence and progression of asthma and allergies. By building upon an existing cohort, ACROSSOLAR offers a unique and cost-effective opportunity to investigate the aetiology of atopic disease in a prospective and cross-generational way.

Risk of Radiation-Induced Malignancy With Heterotopic Ossification Prophylaxis: A Case–Control Analysis

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

Sheybani, Arshin, E-mail: arshin-sheybani@uiowa.edu; TenNapel, Mindi J.; Lack, William D.

2014-07-01

Purpose: To determine the risk of radiation-induced malignancy after prophylactic treatment for heterotopic ossification (HO). Methods and Materials: A matched case–control study was conducted within a population-based cohort of 3489 patients treated either for acetabular fractures with acetabular open reduction internal fixation or who underwent total hip arthroplasty from 1990 to 2009. Record-linkage techniques identified patients who were diagnosed with a malignancy from our state health registry. Patients with a prior history of malignancy were excluded from the cohort. For each documented case of cancer, 2 controls were selected by stratified random sampling from the cohort that did not developmore » a malignancy. Matching factors were sex, age at time of hip treatment, and duration of follow-up. Results: A total of 243 patients were diagnosed with a malignancy after hip treatment. Five patients were excluded owing to inadequate follow-up time in the corresponding control cohort. A cohort of 238 cases (control, 476 patients) was included. Mean follow-up was 10 years, 12 years in the control group. In the cancer cohort, 4% of patients had radiation therapy (RT), compared with 7% in the control group. Of the 9 patients diagnosed with cancer after RT, none occurred within the field. The mean latency period was 5.9 years in the patients who received RT and 6.6 years in the patients who did not. Median (range) age at time of cancer diagnosis in patients who received RT was 62 (43-75) years, compared with 70 (32-92) years in the non-RT patients. An ad hoc analysis was subsequently performed in all 2749 patients who were not matched and found neither an increased incidence of malignancy nor a difference in distribution of type of malignancy. Conclusion: We were unable to demonstrate an increased risk of malignancy in patients who were treated with RT for HO prophylaxis compared with those who were not.« less

Evaluation of prognostic and predictive value of microtubule associated protein tau in two independent cohorts

PubMed Central

2011-01-01

Introduction Microtubule associated proteins (MAPs) endogenously regulate microtubule stabilization and have been reported as prognostic and predictive markers for taxane response. The microtubule stabilizer, MAP-tau, has shown conflicting results. We quantitatively assessed MAP-tau expression in two independent breast cancer cohorts to determine prognostic and predictive value of this biomarker. Methods MAP-tau expression was evaluated in the retrospective Yale University breast cancer cohort (n = 651) using tissue microarrays and also in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC chemotherapy (n = 140), using conventional whole tissue sections. Expression was measured using the AQUA method for quantitative immunofluorescence. Scores were correlated with clinicopathologic variables, survival, and response to therapy. Results Assessment of the Yale cohort using Cox univariate analysis indicated an improved overall survival (OS) in tumors with a positive correlation between high MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with high MAP-tau expression compared to 52% with low expression (P = .006). In TAX 307, high expression was associated with significantly longer median time to tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P = 0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau expression (P = 0.518) or by treatment arm (P = 0.584). Conclusions Quantitative measurement of MAP-tau expression has prognostic value in both cohorts, with high expression associated with longer TTP and OS. Differences by treatment arm or response rate in low versus high MAP-tau groups were not observed, indicating that MAP-tau is not associated with response to taxanes and is not a useful predictive marker for taxane-based chemotherapy. PMID:21888627

SurvMicro: assessment of miRNA-based prognostic signatures for cancer clinical outcomes by multivariate survival analysis.

PubMed

Aguirre-Gamboa, Raul; Trevino, Victor

2014-06-01

MicroRNAs (miRNAs) play a key role in post-transcriptional regulation of mRNA levels. Their function in cancer has been studied by high-throughput methods generating valuable sources of public information. Thus, miRNA signatures predicting cancer clinical outcomes are emerging. An important step to propose miRNA-based biomarkers before clinical validation is their evaluation in independent cohorts. Although it can be carried out using public data, such task is time-consuming and requires a specialized analysis. Therefore, to aid and simplify the evaluation of prognostic miRNA signatures in cancer, we developed SurvMicro, a free and easy-to-use web tool that assesses miRNA signatures from publicly available miRNA profiles using multivariate survival analysis. SurvMicro is composed of a wide and updated database of >40 cohorts in different tissues and a web tool where survival analysis can be done in minutes. We presented evaluations to portray the straightforward functionality of SurvMicro in liver and lung cancer. To our knowledge, SurvMicro is the only bioinformatic tool that aids the evaluation of multivariate prognostic miRNA signatures in cancer. SurvMicro and its tutorial are freely available at http://bioinformatica.mty.itesm.mx/SurvMicro. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Mortality study of civilian employees exposed to contaminated drinking water at USMC Base Camp Lejeune: a retrospective cohort study.

PubMed

Bove, Frank J; Ruckart, Perri Zeitz; Maslia, Morris; Larson, Theodore C

2014-08-13

Two drinking water systems at U.S. Marine Corps Base Camp Lejeune, North Carolina were contaminated with solvents during 1950s-1985. We conducted a retrospective cohort mortality study of 4,647 civilian, full-time workers employed at Camp Lejeune during 1973-1985 and potentially exposed to contaminated drinking water. We selected a comparison cohort of 4,690 Camp Pendleton workers employed during 1973-1985 and unexposed to contaminated drinking water. Mortality follow-up period was 1979-2008. Cause-specific standardized mortality ratios utilized U.S. age-, sex-, race-, and calendar period-specific mortality rates as reference. We used survival analysis to compare mortality rates between Camp Lejeune and Camp Pendleton workers and assess the effects of estimated cumulative contaminant exposures within the Camp Lejeune cohort. Ground water contaminant fate/transport and distribution system models provided monthly estimated contaminant levels in drinking water serving workplaces at Camp Lejeune. The confidence interval (CI) indicated precision of effect estimates. Compared to Camp Pendleton, Camp Lejeune workers had mortality hazard ratios (HRs) >1.50 for kidney cancer (HR = 1.92, 95% CI: 0.58, 6.34), leukemias (HR = 1.59, 95% CI: 0.66, 3.84), multiple myeloma (HR = 1.84, 95% CI: 0.45, 7.58), rectal cancer (HR = 1.65, 95% CI: 0.36, 7.44), oral cavity cancers (HR = 1.93, 95% CI: 0.34, 10.81), and Parkinson's disease (HR = 3.13, 95% CI: 0.76, 12.81). Within the Camp Lejeune cohort, monotonic exposure-response relationships were observed for leukemia and vinyl chloride and PCE, with mortality HRs at the high exposure category of 1.72 (95% CI: 0.33, 8.83) and 1.82 (95% CI: 0.36, 9.32), respectively. Cumulative exposures were above the median for most deaths from cancers of the kidney, esophagus, rectum, prostate, and Parkinson's disease, but small numbers precluded evaluation of exposure-response relationships. The study found elevated HRs in the Camp Lejeune cohort for several causes of death including cancers of the kidney, rectum, oral cavity, leukemias, multiple myeloma, and Parkinson's disease. Only 14% of the Camp Lejeune cohort died by end of follow-up, producing small numbers of cause-specific deaths and wide CIs. Additional follow-up would be necessary to comprehensively assess drinking water exposure effects at the base.

Food-addiction scale measurement in 2 cohorts of middle-aged and older women.

PubMed

Flint, Alan J; Gearhardt, Ashley N; Corbin, William R; Brownell, Kelly D; Field, Alison E; Rimm, Eric B

2014-03-01

Excess weight is a major threat to public health. An addiction-like tendency toward certain foods may contribute to overeating. We aimed to describe the prevalence and associated characteristics in relation to a food-addiction scale in middle-aged and older women. We examined the prevalence and associated characteristics of a food-addiction scale measure in a cross-sectional analysis of 134,175 women participating in 2 ongoing prospective cohort studies of US nurses. Overall, 7839 (5.8%) of the women surveyed met the criteria for food addiction measured by using the modified Yale Food Addiction Scale. The prevalence of food addiction was 8.4% in the younger cohort of women aged 45-64 y and 2.7% in the older cohort of women aged 62-88 y. In the multivariate model, body mass index (BMI; in kg/m²) ≥ 35.0 (compared with 18.5-22.9) was associated with food addiction, a prevalence ratio (PR) of 15.83 (95% CI: 12.58, 19.91) in the younger cohort of women, and a PR of 18.41 (95% CI: 11.63, 29.14) in the older cohort of women. Several other demographic characteristics and other factors were associated with the food-addiction measure in both cohorts of women. To our knowledge, for the first time in a large, US-based population of women, we documented the prevalence of food addiction by using a novel measurement scale in middle-aged and older women. The results may provide insight into the strong association between behavioral attributes of food consumption and the development of obesity.

Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation: A Genome-Wide Analysis among 1,800 South Asians

PubMed Central

Pierce, Brandon L.; Tong, Lin; Chen, Lin S.; Rahaman, Ronald; Argos, Maria; Jasmine, Farzana; Roy, Shantanu; Paul-Brutus, Rachelle; Westra, Harm-Jan; Franke, Lude; Esko, Tonu; Zaman, Rakibuz; Islam, Tariqul; Rahman, Mahfuzar; Baron, John A.; Kibriya, Muhammad G.; Ahsan, Habibul

2014-01-01

A large fraction of human genes are regulated by genetic variation near the transcribed sequence (cis-eQTL, expression quantitative trait locus), and many cis-eQTLs have implications for human disease. Less is known regarding the effects of genetic variation on expression of distant genes (trans-eQTLs) and their biological mechanisms. In this work, we use genome-wide data on SNPs and array-based expression measures from mononuclear cells obtained from a population-based cohort of 1,799 Bangladeshi individuals to characterize cis- and trans-eQTLs and determine if observed trans-eQTL associations are mediated by expression of transcripts in cis with the SNPs showing trans-association, using Sobel tests of mediation. We observed 434 independent trans-eQTL associations at a false-discovery rate of 0.05, and 189 of these trans-eQTLs were also cis-eQTLs (enrichment P<0.0001). Among these 189 trans-eQTL associations, 39 were significantly attenuated after adjusting for a cis-mediator based on Sobel P<10-5. We attempted to replicate 21 of these mediation signals in two European cohorts, and while only 7 trans-eQTL associations were present in one or both cohorts, 6 showed evidence of cis-mediation. Analyses of simulated data show that complete mediation will be observed as partial mediation in the presence of mediator measurement error or imperfect LD between measured and causal variants. Our data demonstrates that trans-associations can become significantly stronger or switch directions after adjusting for a potential mediator. Using simulated data, we demonstrate that this phenomenon is expected in the presence of strong cis-trans confounding and when the measured cis-transcript is correlated with the true (unmeasured) mediator. In conclusion, by applying mediation analysis to eQTL data, we show that a substantial fraction of observed trans-eQTL associations can be explained by cis-mediation. Future studies should focus on understanding the mechanisms underlying widespread cis-mediation and their relevance to disease biology, as well as using mediation analysis to improve eQTL discovery. PMID:25474530

Detection of 22 common leukemic fusion genes using a single-step multiplex qRT-PCR-based assay.

PubMed

Lyu, Xiaodong; Wang, Xianwei; Zhang, Lina; Chen, Zhenzhu; Zhao, Yu; Hu, Jieying; Fan, Ruihua; Song, Yongping

2017-07-25

Fusion genes generated from chromosomal translocation play an important role in hematological malignancies. Detection of fusion genes currently employ use of either conventional RT-PCR methods or fluorescent in situ hybridization (FISH), where both methods involve tedious methodologies and require prior characterization of chromosomal translocation events as determined by cytogenetic analysis. In this study, we describe a real-time quantitative reverse transcription PCR (qRT-PCR)-based multi-fusion gene screening method with the capacity to detect 22 fusion genes commonly found in leukemia. This method does not require pre-characterization of gene translocation events, thereby facilitating immediate diagnosis and therapeutic management. We performed fluorescent qRT-PCR (F-qRT-PCR) using a commercially-available multi-fusion gene detection kit on a patient cohort of 345 individuals comprising 108 cases diagnosed with acute myeloid leukemia (AML) for initial evaluation; remaining patients within the cohort were assayed for confirmatory diagnosis. Results obtained by F-qRT-PCR were compared alongside patient analysis by cytogenetic characterization. Gene translocations detected by F-qRT-PCR in AML cases were diagnosed in 69.4% of the patient cohort, which was comparatively similar to 68.5% as diagnosed by cytogenetic analysis, thereby demonstrating 99.1% concordance. Overall gene fusion was detected in 53.7% of the overall patient population by F-qRT-PCR, 52.9% by cytogenetic prediction in leukemia, and 9.1% in non-leukemia patients by both methods. The overall concordance rate was calculated to be 99.0%. Fusion genes were detected by F-qRT-PCR in 97.3% of patients with CML, followed by 69.4% with AML, 33.3% with acute lymphoblastic leukemia (ALL), 9.1% with myelodysplastic syndromes (MDS), and 0% with chronic lymphocytic leukemia (CLL). We describe the use of a F-qRT-PCR-based multi-fusion gene screening method as an efficient one-step diagnostic procedure as an effective alternative to lengthy conventional diagnostic procedures requiring both cytogenetic analysis followed by targeted quantitative reverse transcription (qRT-PCR) methods, thus allowing timely patient management.

The marriage boom and marriage bust in the United States: An age-period-cohort analysis.

PubMed

Schellekens, Jona

2017-03-01

In the 1950s and 1960s there was an unprecedented marriage boom in the United States. This was followed in the 1970s by a marriage bust. Some argue that both phenomena are cohort effects, while others argue that they are period effects. The study reported here tested the major period and cohort theories of the marriage boom and bust, by estimating an age-period-cohort model of first marriage for the years 1925-79 using census microdata. The results of the analysis indicate that the marriage boom was mostly a period effect, although there were also cohort influences. More specifically, the hypothesis that the marriage boom was mostly a response to rising wages is shown to be consistent with the data. However, much of the marriage bust can be accounted for by unidentified cohort influences, at least until 1980.

Caffeine intake from coffee or tea and cognitive disorders: a meta-analysis of observational studies.

PubMed

Kim, Young-Seok; Kwak, Sang Mi; Myung, Seung-Kwon

2015-01-01

Observational epidemiological studies such as cross-sectional, case-control, and cohort studies have reported inconsistent findings regarding the association between caffeine intake from coffee or tea and the risk of cognitive disorders such as dementia, Alzheimer's disease, cognitive impairment, and cognitive decline. We searched PubMed and EMBASE in September 2014. Three evaluators independently extracted and reviewed articles, based on predetermined selection criteria. Out of 293 articles identified through the search and bibliographies of relevant articles, 20 epidemiological studies from 19 articles, which involved 31,479 participants (8,398 in six cross-sectional studies, 4,601 in five case-control studies, and 19,918 in nine cohort studies), were included in the final analysis. The pooled odds ratio (OR) or relative risk (RR) of caffeine intake from coffee or tea for cognitive disorders (dementia, Alzheimer's disease, cognitive impairment, and cognitive decline) was 0.82 (95% confidence interval [CI], 0.67-1.01, I² = 63.2%) in a random-effects meta-analysis. In the subgroup meta-analysis by caffeine sources, the summary OR or RR of coffee intake was 0.83 (95% CI, 0.70-0.98; I² = 44.8%). However, in the subgroup meta-analysis by study design, the summary estimates (RR or OR) of coffee intake for cognitive disorders were 0.70 (95% CI, 0.50-0.98; I² = 42.0%) for cross-sectional studies, 0.82 (95% CI, 0.55-1.24; I² = 33.4%) for case-control studies, and 0.90 (95% CI, 0.59-1.36; I² = 60.0%) for cohort studies. This meta-analysis found that caffeine intake from coffee or tea was not associated with the risk of cognitive disorders.

Weight-for-length trajectories in the first year of life in children of mothers with eating disorders in a large Norwegian cohort

PubMed Central

Perrin, Eliana M.; Von Holle, Ann; Zerwas, Stephanie; Skinner, Asheley Cockrell; Reba-Harrelson, Lauren; Hamer, Robert M.; Stoltenberg, Camilla; Torgersen, Leila; Reichborn-Kjennerud, Ted; Bulik, Cynthia M.

2015-01-01

Objective To describe weight-for-length (WFL) trajectories in the children (birth-12 months) of mothers with and without eating disorders. Methods This study is based on the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. We categorized women (N=57,185) based on diagnosis prior to and during pregnancy: anorexia nervosa (AN), bulimia nervosa (BN), eating disorder not otherwise specified-purging subtype (EDNOS-P), binge eating disorder (BED), or no eating disorder (no-ED). The primary analysis included a shape invariant model fitted with non-linear mixed effects to compare growth rates across eating disorder subtypes. Results The children of mothers reporting any eating disorder had a lower WFL growth rate from birth--12 months than the children of mothers without eating disorders, even after adjusting for relative birth weight and some confounders known to affect growth. Discussion In this cohort, child WFL was related to maternal eating disorder status before and/or during pregnancy. These differences in growth trajectories warrant further study of long-term health outcomes and, if replicated, tailoring counseling to mothers with eating disorders during pregnancy. PMID:24782279

Increased subsequent risk of inflammatory bowel disease association in patients with chronic pancreatitis: a nationwide population-based cohort study.

PubMed

Chen, Yu-Long; Hsu, Chin-Wang; Cheng, Cheng-Chung; Yiang, Giou-Teng; Lin, Chin-Sheng; Lin, Cheng-Li; Sung, Fung-Chang; Liang, Ji-An

2017-06-01

To investigate the relationship between chronic pancreatitis (CP) and inflammatory bowel disease (IBD) in a large population-based cohort study. Data was obtained from the Taiwan National Health Insurance Research Database. The cohort study comprised 17,796 patients newly diagnosed with CP between 2000 and 2010 and 71,164 matched controls. A Cox proportional hazards model was used for evaluating the risk of IBD in the CP and comparison cohorts. When examined with a mean follow-up period of 4.87 and 6.04 years for the CP and comparison cohorts, respectively, the overall incidence of IBD was 10.3 times higher in the CP cohort than in the comparison cohort (5.75 vs. 0.56 per 10,000 person-years). Compared with the comparison cohort, the CP cohort exhibited a higher risk of IBD, irrespective of age, sex, and presence or absence of comorbidities. Moreover, the CP cohort was associated with a significantly higher risk of Crohn's disease (adjusted hazard ratio [aHR] = 12.9, 95% confidence interval [CI] = 5.15-32.5) and ulcerative colitis (aHR = 2.80, 95% CI = 1.00-7.86). This nationwide population-based cohort study revealed a significantly higher risk of IBD in patients with CP compared with control group. Clinicians should notice this association to avoid delayed diagnosis of IBD in patients with CP.

What Is Heartburn Worth?

PubMed Central

Heudebert, Gustavo R; Centor, Robert M; Klapow, Joshua C; Marks, Robert; Johnson, Lawrence; Wilcox, C Mel

2000-01-01

OBJECTIVE T o determine the best treatment strategy for the management of patients presenting with symptoms consistent with uncomplicated heartburn. METHODS We performed a cost-utility analysis of 4 alternatives: empirical proton pump inhibitor, empirical histamine2-receptor antagonist, and diagnostic strategies consisting of either esophagogastroduodenoscopy (EGD) or an upper gastrointestinal series before treatment. The time horizon of the model was 1 year. The base case analysis assumed a cohort of otherwise healthy 45-year-old individuals in a primary care practice. MAIN RESULTS Empirical treatment with a proton pump inhibitor was projected to provide the greatest quality-adjusted survival for the cohort. Empirical treatment with a histamine2receptor antagonist was projected to be the least costly of the alternatives. The marginal cost-effectiveness of using a proton pump inhibitor over a histamine2-receptor antagonist was approximately $10,400 per quality-adjusted life year (QALY) gained in the base case analysis and was less than $50,000 per QALY as long as the utility for heartburn was less than 0.95. Both diagnostic strategies were dominated by proton pump inhibitor alternative. CONCLUSIONS Empirical treatment seems to be the optimal initial management strategy for patients with heartburn, but the choice between a proton pump inhibitor or histamine2-receptor antagonist depends on the impact of heartburn on quality of life. PMID:10718898

Cost-effectiveness analysis of the introduction of the human papillomavirus vaccine in Honduras.

PubMed

Aguilar, Ida Berenice Molina; Mendoza, Lourdes Otilia; García, Odalys; Díaz, Iris; Figueroa, Jacqueline; Duarte, Rosa María; Perdomo, Gabriel; Garcia, Ana Gabriela Felix; Janusz, Cara Bess

2015-05-07

Cervical cancer is the leading cause of cancer deaths in Honduras. With the availability of a vaccine to prevent human papillomavirus (HPV), the causative agent for cervical cancer, the Honduran Secretary of Health undertook a cost-effectiveness analysis of introducing the HPV vaccine to support their national decision-making process. A national multidisciplinary team conducted this analysis with the CERVIVAC model, developed by the London School of Hygiene and Tropical Medicine in collaboration with the Pan American Health Organization's ProVac Initiative. The cumulative costs and health benefits of introducing the HPV vaccine were assessed over the lifetime of one single cohort of 11-year-old girls. We assumed a three-dose series with 95% vaccination coverage of the cohort using a mixture of school-based and facility-based delivery. To estimate national cervical cancer cases and deaths, we used United Nations demographic projections and GLOBOCAN estimates based on registry data from El Salvador, Guatemala, and Nicaragua. Based on estimates from the World Health Organization (WHO) and the Division of Intensified Cooperation with Countries (ICO), we assumed that 70% of cervical cancer would be due to vaccine types HPV16 and HPV18. We used a vaccine dose price of US$ 13.45 and evidence from the scientific literature to estimate vaccine effectiveness. National information was used to estimate health service utilization and costs of cervical cancer treatment. All costs and health benefits were discounted at 3%. Upon fully vaccinating 86,906 11-year old girls, 2250 (undiscounted) cervical cancer cases and 1336 (undiscounted) deaths would be prevented over the lifetime of the cohort. After discounting future health benefits at 3% per year, the equivalent cases and deaths prevented were 421 and 170. HPV vaccination is estimated to cost around US$ 5 million per vaccinated cohort, but this would be offset by around US$ 1 million in avoided costs borne by the government to treat cervical cancer. Furthermore, 4349 discounted disability adjusted life years (DALYs) could be avoided at a cost of US$ 926 per DALY avoided, making HPV vaccination in Honduras a highly cost-effective intervention. The net cost of HPV vaccination per DALY avoided is less than the WHO threshold for cost-effectiveness. However, at a cost of around US$ 5 million per vaccinated cohort, an important element to consider in this discussion is the budgetary implications that the introduction of the HPV vaccine would cause for the country. When comparing the costs and benefits of HPV vaccine introduction in Honduras, it is clear that this intervention would be highly cost-effective and that the intervention would greatly reduce cervical cancer disease. For these reasons, it is in the country's best interest to explore financing opportunities that could support the vaccine's introduction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort

PubMed Central

Budhathoki, Sanjeev; Hidaka, Akihisa; Sawada, Norie; Tanaka-Mizuno, Sachiko; Kuchiba, Aya; Charvat, Hadrien; Goto, Atsushi; Kojima, Satoshi; Sudo, Natsuki; Shimazu, Taichi; Sasazuki, Shizuka; Inoue, Manami; Tsugane, Shoichiro; Iwasaki, Motoki

2018-01-01

Abstract Objective To evaluate the association between pre-diagnostic circulating vitamin D concentration and the subsequent risk of overall and site specific cancer in a large cohort study. Design Nested case-cohort study within the Japan Public Health Center-based Prospective Study cohort. Setting Nine public health centre areas across Japan. Participants 3301 incident cases of cancer and 4044 randomly selected subcohort participants. Exposure Plasma concentration of 25-hydroxyvitamin D measured by enzyme immunoassay. Participants were divided into quarters based on the sex and season specific distribution of 25-hydroxyvitamin D among subcohorts. Weighted Cox proportional hazard models were used to calculate the multivariable adjusted hazard ratios for overall and site specific cancer across categories of 25-hydroxyvitamin D concentration, with the lowest quarter as the reference. Main outcome measure Incidence of overall or site specific cancer. Results Plasma 25-hydroxyvitamin D concentration was inversely associated with the risk of total cancer, with multivariable adjusted hazard ratios for the second to fourth quarters compared with the lowest quarter of 0.81 (95% confidence interval 0.70 to 0.94), 0.75 (0.65 to 0.87), and 0.78 (0.67 to 0.91), respectively (P for trend=0.001). Among the findings for cancers at specific sites, an inverse association was found for liver cancer, with corresponding hazard ratios of 0.70 (0.44 to 1.13), 0.65 (0.40 to 1.06), and 0.45 (0.26 to 0.79) (P for trend=0.006). A sensitivity analysis showed that alternately removing cases of cancer at one specific site from total cancer cases did not substantially change the overall hazard ratios. Conclusions In this large prospective study, higher vitamin D concentration was associated with lower risk of total cancer. These findings support the hypothesis that vitamin D has protective effects against cancers at many sites. PMID:29514781

Survival in pediatric medulloblastoma: a population-based observational study to improve prognostication.

PubMed

Weil, Alexander G; Wang, Anthony C; Westwick, Harrison J; Ibrahim, George M; Ariani, Rojine T; Crevier, Louis; Perreault, Sebastien; Davidson, Tom; Tseng, Chi-Hong; Fallah, Aria

2017-03-01

Medulloblastoma is the most common form of brain malignancy of childhood. The mainstay of epidemiological data regarding childhood medulloblastoma is derived from case series, hence population-based studies are warranted to improve the accuracy of survival estimates. To utilize a big-data approach to update survival estimates in a contemporary cohort of children with medulloblastoma. We performed a population-based retrospective observational cohort study utilizing the Surveillance, Epidemiology, and End Results Program database that captures all children, less than 20 years of age, between 1973 and 2012 in 18 geographical regions representing 28% of the US population. We included all participants with a presumed or histologically diagnosis of medulloblastoma. The main outcome of interest is survivors at 1, 5 and 10 years following diagnosis. A cohort of 1735 children with a median (interquartile range) age at diagnosis of 7 (4-11) years, with a diagnosis of medulloblastoma were identified. The incidence and prevalence of pediatric medulloblastoma has remained stable over the past 4 decades. There is a critical time point at 1990 when the overall survival has drastically improved. In the contemporary cohort (1990 onwards), the percentage of participants alive was 86, 70 and 63% at 1, 5 and 10 years, respectively. Multivariate Cox-Regression model demonstrated Radiation (HR 0.37; 95% CI 0.30-0.46, p < 0.001) and Surgery (HR 0.42; 95% CI 0.30-0.58, p < 0.001) independently predict survival. The probability of mortality from a neurological cause is <5% in patients who are alive 8 years following diagnosis. The SEER cohort analysis demonstrates significant improvements in pediatric medulloblastoma survival. In contrast to previous reports, the majority of patients survive in the modern era, and those alive 8 years following initial diagnosis are likely a long-term survivor. The importance of minimizing treatment-related toxicity is increasingly apparent given the likelihood of long-term survival.

Somatoform disorder as a predictor of interstitial cystitis/bladder pain syndrome: Evidence from a nested case-control study and a retrospective cohort study.

PubMed

Chen, I-Chun; Lee, Ming-Huei; Lin, Hsuan-Hung; Wu, Shang-Liang; Chang, Kun-Min; Lin, Hsiu-Ying

2017-05-01

Interstitial cystitis/bladder pain syndrome (IC/BPS) has several well-known comorbid psychiatric manifestations, including insomnia, anxiety, and depression. We hypothesized that somatoform disorder, which is a psychosomatic disease, can be used as a sensitive psychiatric phenotype of IC/BPS. We investigated whether somatoform disorder increases the risk of IC/BPS.A nested case-control study and a retrospective cohort study were followed up over a 12-year period (2002-2013) in the Taiwan Health Insurance Reimbursement Database. In the nested case-control study, 1612 patients with IC/BPS were matched in a 1:2 ratio to 3224 controls based on propensity scores. The odds ratio for somatoform disorder was calculated using conditional logistic regression analysis. In the retrospective cohort study, 1436 patients with somatoform disorder were matched in a 1:2 ratio to 2872 patients with nonsomatoform disorder based on propensity scores. Cox regression analysis was used to estimate the hazard ratio associated with the development of IC/BPS in patients with somatoform disorder, and the cumulative survival probability was tested using the Kaplan-Meier analysis.We found that the odds ratio for somatoform disorder was 2.46 (95% confidence interval [CI], 1.05-5.76). Although the average time until IC/BPS development in the control subjects was 11.5 ± 1.3 years, this interval was shorter in patients with somatoform disorder (6.3 ± 3.6 years). The hazard ratio for developing IC/BPS was 2.50 (95% CI 1.23-5.58); the adjusted hazard ratio was 2.26 (95% CI 1.002-5.007). The patients and controls also differed significantly in their cumulative survival probability for IC/BPS (log rank P < .05).Evidence from the nested case-control study and retrospective cohort study consistently indicated that somatoform disorder increases the risk for IC/BPS. Our study suggests that somatoform disorder can be used as a sensitive psychiatric phenotype to predict IC/BPS. Any past history of somatoform disorder should be documented while examining patients with IC/BPS.

Is Child Abuse Associated with Adolescent Obesity? A Population Cohort Study.

PubMed

Hawton, Katherine; Norris, Tom; Crawley, Esther; Shield, Julian P H

Child abuse is associated with obesity in adulthood through multiple mechanisms. However, little is known about the relationship between abuse and obesity during adolescence. The aim of this study was to investigate, using a birth cohort, whether there is an association between child abuse and overweight or obesity in adolescence. This study utilizes data from the Avon Longitudinal Study of Parents and Children, a prospective cohort study based in South West England. Using data from the 4205 children with complete data at 13 and 16 years, we analyzed body mass index (BMI) and anonymous parental report of abuse. Abuse was categorized as emotional, physical, or sexual. A sub-sample of 3429 had BMI recorded at 18 years, enabling a longitudinal analysis of BMI trajectories. Using linear and logistic regression analysis, adjusting for sex and family adversity, no association was found between child abuse and BMI, BMI Z-scores, overweight, or obesity, at 13 or 16 years, with all confidence intervals straddling the null. There was weak evidence of a negative association between physical and emotional abuse and BMI trajectories between 13 and 18 years. No relationship was found between child abuse and adolescent obesity in this cohort. This challenges the assumption that adolescent obesity is linked to previous child abuse, as demonstrated for obesity in adult life. A further longitudinal study utilizing both parental and child reports with data record linkage, to improve reporting of abuse, and including neglect as an abuse category, would be desirable.

Clinical Characteristics of Patients With Renal Cell Carcinoma and Metastasis to the Thyroid Gland.

PubMed

Jackson, Gregory; Fino, Nora; Bitting, Rhonda L

2017-01-01

Renal cell carcinoma (RCC) is the most common malignancy to metastasize to the thyroid gland. The aims of this study are as follows: (1) to analyze the clinical characteristics of patients with thyroid involvement of RCC and (2) in patients with RCC thyroid metastasis, to determine whether RCC metastasis to glandular organs only portends a better prognosis compared with other patterns of RCC metastasis. Patients from Wake Forest Baptist Medical Center (WFBMC) diagnosed with thyroid metastasis from RCC were identified and medical records retrospectively examined. A systematic review of the literature for cases of RCC involving the thyroid gland was also performed. The clinical characteristics of the institutional cohort and the cases from the literature review were compared. Descriptive statistical analysis was performed, and overall survival (OS) was summarized using Kaplan-Meier methods. The median OS for the WFBMC cohort was 56.4 months. In the literature review cohort, OS of patients with RCC thyroid metastasis was 213.6 months, and there was no statistically significant survival difference based on the site of metastasis. Median survival after thyroid metastasis from RCC for the WFBMC and literature cohort was 21.6 and 45.6 months, respectively. Metastatic RCC should be included in the differential of a new thyroid mass. Treatment directed at the thyroid metastasis results in prolonged survival in some cases. Further analysis into the genomic differences and mechanisms of thyroid metastasis is warranted.

Students' Engagement with a Collaborative Wiki Tool Predicts Enhanced Written Exam Performance

ERIC Educational Resources Information Center

Stafford, Tom; Elgueta, Herman; Cameron, Harriet

2014-01-01

We introduced voluntary wiki-based exercises to a long-running cognitive psychology course, part of the core curriculum for an undergraduate degree in psychology. Over 2 yearly cohorts, students who used the wiki more also scored higher on the final written exam. Using regression analysis, it is possible to account for students' tendency to score…

Relationship between body fat and BMI in a U.S. Hispanic population-based cohort study: Results from HCHS/SOL

USDA-ARS?s Scientific Manuscript database

To evaluate the percentage of body fat (%BF)-BMI relationship, identify %BF levels corresponding to adult BMI cut points, and examine %BF-BMI agreement in a diverse Hispanic/Latino population. %BF by bioelectrical impedance analysis was corrected against %BF by 18O dilution in 434 participants of th...

Time trends in exposure of cattle to bovine spongiform encephalopathy and cohort effect in France and Italy: value of the classical Age-Period-Cohort approach.

PubMed

Sala, Carole; Ru, Giuseppe

2009-09-18

The Age-Period-Cohort (APC) analysis is routinely used for time trend analysis of cancer incidence or mortality rates, but in veterinary epidemiology, there are still only a few examples of this application. APC models were recently used to model the French epidemic assuming that the time trend for BSE was mainly due to a cohort effect in relation to the control measures that may have modified the BSE exposure of cohorts over time. We used a categorical APC analysis which did not require any functional form for the effect of the variables, and examined second differences to estimate the variation of the BSE trend. We also reanalysed the French epidemic and performed a simultaneous analysis of Italian data using more appropriate birth cohort categories for comparison. We used data from the exhaustive surveillance carried out in France and Italy between 2001 and 2007, and comparatively described the trend of the epidemic in both countries. At the end, the shape and irregularities of the trends were discussed in light of the main control measures adopted to control the disease. In Italy a decrease in the epidemic became apparent from 1996, following the application of rendering standards for the processing of specific risk material (SRM). For the French epidemic, the pattern of second differences in the birth cohorts confirmed the beginning of the decrease from 1995, just after the implementation of the meat and bone meal (MBM) ban for all ruminants (1994). The APC analysis proved to be highly suitable for the study of the trend in BSE epidemics and was helpful in understanding the effects of management and control of the disease. Additionally, such an approach may help in the implementation of changes in BSE regulations.

Contemporary management of frontal sinus mucoceles: a meta-analysis.

PubMed

Courson, Andy M; Stankiewicz, James A; Lal, Devyani

2014-02-01

To analyze trends in the surgical management of frontal and fronto-ethmoid mucoceles through meta-analysis. Meta-analysis and case series. A systematic literature review on surgical management of frontal and fronto-ethmoid mucoceles was conducted. Studies were divided into historical (1975-2001) and contemporary (2002-2012) groups. A meta-analysis of these studies was performed. The historical and contemporary cohorts were compared (surgical approach, recurrence, and complications). To study evolution in surgical management, a senior surgeon's experience over 28 years was analyzed separately. Thirty-one studies were included for meta-analysis. The historical cohort included 425 mucoceles from 11 studies. The contemporary cohort included 542 mucoceles from 20 studies. More endoscopic techniques were used in the contemporary versus historical cohort (53.9% vs. 24.7%; P = <0.001). In the authors' series, a higher percentage was treated endoscopically (82.8% of 122 mucoceles). Recurrence (P = 0.20) and major complication (P = 0.23) rates were similar between cohorts. Minor complication rates were superior for endoscopic techniques in both cohorts (P = 0.02 historical; P = <0.001 contemporary). In the historical cohort, higher recurrence was noted in the external group (P = 0.03). Results from endoscopic and open approaches are comparable. Although endoscopic techniques are being increasingly adopted, comparison with our series shows that more cases could potentially be treated endoscopically. Frequent use of open approaches may reflect efficacy, or perhaps lack of expertise and equipment required for endoscopic management. Most contemporary authors favor endoscopic management, limiting open approaches for specific indications (unfavorable anatomy, lateral disease, and scarring). N/A. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

THE IMPACT OF AGE ON THE INNATE IMMUNE RESPONSE AND OUTCOMES AFTER SEVERE SEPSIS/SEPTIC SHOCK IN TRAUMA AND SURGICAL INTENSIVE CARE UNIT PATIENTS.

PubMed

Brakenridge, Scott C; Efron, Philip A; Stortz, Julie A; Ozrazgat-Baslanti, Teczan; Ghita, Gabriela; Wang, Zhongkai; Bihorac, Azra; Mohr, Alicia M; Brumback, Babette A; Moldawer, Lyle L; Moore, Frederick A

2018-04-02

Advancing age is a strong risk factor for adverse outcomes across multiple disease processes. However, septic surgical and trauma patients are unique in they incur two or more inflammatory insults. The effects of advanced age on sepsis pathophysiology and outcomes remain unclear. We performed a single center, prospective observational cohort study of Surgical ICU patients with severe sepsis/septic shock. Peripheral blood was collected for genomic, cytokine and biomarker analysis at 0.5, 1, 4, 7, 14, 21 and 28 days after sepsis onset. Based on sensitivity analysis, cohorts were defined as "young" (<55 years) and "aged" (≥55 years). We compared age-defined cohorts to determine differences in patient characteristics, biomarker profiles and clinical outcomes. The cohort included 173 patients with severe sepsis (n=93; 53.8%) or septic shock (n=80; 46.2%), with a mean age of 60.9 (±14.5) years. Intra-abdominal sepsis was the leading source (n=81; 46.8%), followed by NSTI (n=33, 19.1%) and pneumonia (n=30; 17.3%). Aged patients had a higher comorbidity burden, but were otherwise similar to the young cohort. The aged cohort had a higher severity of early physiologic derangement (median APACHE II, 23 vs 18, p=0.002), greater incidence of multiple organ failure (MOF; 64.3% vs 40.4%, p=0.006), and hospital mortality (15.9% vs 2.1%, p=0.016). Six-month mortality was significantly higher in the aged as compared to young cohort (31% vs 9%, p=0.003). Aged septic patients biomarker trajectories suggestive of persistent immunosuppression (Absolute lymphocyte count, sPDL-1) and catabolism (Urine 3MH-Cr ratio, IGF, IGF1BP3, albumin) out to 28 days after sepsis. Aged, critically ill surgical patients have greater organ dysfunction, and incidence of adverse clinical outcomes after sepsis. Biomarker profiles suggest an immunophenotype of persistent immunosuppression and catabolism. Advanced age may necessitate novel therapeutic strategies to promote multi-system organ recovery and improve survival after sepsis. Level II, prognostic.

Adjuvant NY-ESO-1 vaccine immunotherapy in high-risk resected melanoma: a retrospective cohort analysis.

PubMed

Lattanzi, Michael; Han, Joseph; Moran, Una; Utter, Kierstin; Tchack, Jeremy; Sabado, Rachel Lubong; Berman, Russell; Shapiro, Richard; Huang, Hsin-Hui; Osman, Iman; Bhardwaj, Nina; Pavlick, Anna C

2018-05-18

Cancer-testis antigen NY-ESO-1 is a highly immunogenic melanoma antigen which has been incorporated into adjuvant vaccine clinical trials. Three such early-phase trials were conducted at our center among patients with high-risk resected melanoma. We herein report on the pooled long-term survival outcomes of these patients in comparison to historical controls. All melanoma patients treated at NYU Langone Health under any of three prospective adjuvant NY-ESO-1 vaccine trials were retrospectively pooled into a single cohort. All such patients with stage III melanoma were subsequently compared to historical control patients identified via a prospective institutional database with protocol-driven follow-up. Survival times were calculated using the Kaplan-Meier method, and Cox proportional hazard models were employed to identify significant prognostic factors and control for confounding variables. A total of 91 patients were treated with an NY-ESO-1 vaccine for the treatment of high-risk resected melanoma. Of this group, 67 patients were stage III and were selected for comparative analysis with 123 historical control patients with resected stage III melanoma who received no adjuvant therapy. Among the pooled vaccine cohort (median follow-up 61 months), the estimated median recurrence-free survival was 45 months, while the median overall survival was not yet reached. In the control cohort of 123 patients (median follow-up 30 months), the estimated median recurrence-free and overall survival were 22 and 58 months, respectively. Within the retrospective stage III cohort, NY-ESO-1 vaccine was associated with decreased risk of recurrence (HR = 0.56, p < 0.01) and death (HR = 0.51, p = 0.01). Upon controlling for sub-stage, the adjuvant NY-ESO-1 clinical trial cohort continued to exhibit decreased risk of recurrence (HR = 0.45, p < 0.01) and death (HR = 0.40, p < 0.01). In this small retrospective cohort of resected stage III melanoma patients, adjuvant NY-ESO-1 vaccine immunotherapy was associated with longer recurrence-free and overall survival relative to historical controls. These data support the continued investigation of adjuvant NY-ESO-1 based immunotherapy regimens in melanoma.

An efficient Bayesian meta-analysis approach for studying cross-phenotype genetic associations

PubMed Central

Majumdar, Arunabha; Haldar, Tanushree; Bhattacharya, Sourabh; Witte, John S.

2018-01-01

Simultaneous analysis of genetic associations with multiple phenotypes may reveal shared genetic susceptibility across traits (pleiotropy). For a locus exhibiting overall pleiotropy, it is important to identify which specific traits underlie this association. We propose a Bayesian meta-analysis approach (termed CPBayes) that uses summary-level data across multiple phenotypes to simultaneously measure the evidence of aggregate-level pleiotropic association and estimate an optimal subset of traits associated with the risk locus. This method uses a unified Bayesian statistical framework based on a spike and slab prior. CPBayes performs a fully Bayesian analysis by employing the Markov Chain Monte Carlo (MCMC) technique Gibbs sampling. It takes into account heterogeneity in the size and direction of the genetic effects across traits. It can be applied to both cohort data and separate studies of multiple traits having overlapping or non-overlapping subjects. Simulations show that CPBayes can produce higher accuracy in the selection of associated traits underlying a pleiotropic signal than the subset-based meta-analysis ASSET. We used CPBayes to undertake a genome-wide pleiotropic association study of 22 traits in the large Kaiser GERA cohort and detected six independent pleiotropic loci associated with at least two phenotypes. This includes a locus at chromosomal region 1q24.2 which exhibits an association simultaneously with the risk of five different diseases: Dermatophytosis, Hemorrhoids, Iron Deficiency, Osteoporosis and Peripheral Vascular Disease. We provide an R-package ‘CPBayes’ implementing the proposed method. PMID:29432419

A Cohort, Is a Cohort, Is a Cohort...or Is It?

ERIC Educational Resources Information Center

Pemberton, Cynthia Lee A.; Akkary, Rima Karami

2010-01-01

This paper presents findings from a multi-year qualitative study based upon life-history narratives of women pursuing doctoral degrees in Educational Leadership. This paper focuses on findings specific to educational cohort models, and suggests that perhaps, at least for women, naturally emergent cohorts--born of relationships of choice--may be…

Inter-cohort growth for three tropical resources: tilapia, octopus and lobster.

PubMed

Velázquez-Abunader, Iván; Gómez-Muñoz, Victor Manuel; Salas, Silvia; Ruiz-Velazco, Javier M J

2015-09-01

Growth parameters are an important component for the stock assessment of exploited aquatic species. However, it is often difficult to apply direct methods to estimate growth and to analyse the differences between males and females, particularly in tropical areas. The objective of this study was to analyse the inter-cohort growth of three tropical resources and discuss the possible fisheries management implications. A simple method was used to compare individual growth curves obtained from length frequency distribution analysis, illustrated by case studies of three tropical species from different aquatic environments: tilapia (Oreochromis aureus), red octopus (Octopus maya) and the Caribbean spiny lobster (Panulirus argus). The analysis undertaken compared the size distribution of males and females of a given cohort through modal progression analysis. The technique used proved to be useful for highlighting the differences in growth between females and males of a specific cohort. The potential effect of extrinsic and intrinsic factors on the organism's development as reflected in the size distribution of the cohorts is discussed.

Mobile and traditional cognitive behavioral therapy programs for generalized anxiety disorder: A cost-effectiveness analysis

PubMed Central

2018-01-01

Background Generalized anxiety disorder (GAD) is a debilitating mental health illness that affects approximately 3.1% of U.S. adults and can be treated with cognitive behavioral therapy (CBT). With the emergence of digital health technologies, mobile CBT may be a cost-effective way to deliver care. We developed an analysis framework to quantify the cost-effectiveness of internet-based CBT for individuals with GAD. As a case study, we examined the potential value of a new mobile-delivered CBT program for GAD. Methods We developed a Markov model of GAD health states combined with a detailed economic analysis for a cohort of adults with GAD in the U.S. In our case study, we used pilot program efficacy data to evaluate a mobile CBT program as either prevention or treatment only and compared the strategies to traditional CBT and no CBT. Traditional CBT efficacy was estimated from clinical trial results. We calculated discounted incremental costs and quality-adjusted life-years (QALYs) over the cohort lifetime. Case study results In the base case, for a cohort of 100,000 persons with GAD, we found that mobile CBT is cost-saving. It leads to a gain of 34,108 QALYs and 81,492 QALYs and a cost reduction of $2.23 billion and $4.54 billion when compared to traditional CBT and no CBT respectively. Results were insensitive to most model inputs and mobile CBT remained cost-saving in almost all scenarios. Limitations The case study was conducted for illustrative purposes and used mobile CBT efficacy data from a small pilot program; the analysis should be re-conducted once robust efficacy data is available. The model was limited in its ability to measure the effectiveness of CBT in combination with pharmacotherapy. Conclusions Mobile CBT may lead to improved health outcomes at lower costs than traditional CBT or no intervention and may be effective as either prevention or treatment. PMID:29300754

Development and Validation of Web-Based Nomograms to Precisely Predict Conditional Risk of Site-Specific Recurrence for Patients With Completely Resected Non-small Cell Lung Cancer: A Multiinstitutional Study.

PubMed

Zhang, Yang; Zheng, Difan; Xie, Juntao; Li, Yuan; Wang, Yiyang; Li, Chenguang; Xiang, Jiaqing; Zhang, Yawei; Hu, Hong; Sun, Yihua; Chen, Haiquan

2018-06-15

There is currently no consensus regarding the optimal postoperative follow-up strategy for patients with completely resected non-small cell lung cancer (NSCLC). We aimed to develop web-based nomograms to precisely predict site-specific postoperative recurrence in patients with NSCLC and to guide individual surveillance strategies including when to follow up and what diagnostic tests to perform. We investigated the pattern of recurrence in a series of 2,017 patients with NSCLC (squamous cell carcinoma and nonlepidic invasive adenocarcinoma) who underwent complete surgical resection at Fudan University Shanghai Cancer Center (development cohort), and developed web-based clinicopathologic prediction models for conditional risk of site-specific recurrence based on Cox regression. The variables used in the analysis included sex, age, smoking history, tumor size, tumor histology, lymphovascular invasion, visceral pleural invasion, and pathologic TNM stage. A separate cohort of 3,308 patients with NSCLC from Shanghai Chest Hospital was used for external validation. In the development cohort and the external validation cohort for the established nomograms to predict overall recurrence, thorax recurrence, abdomen recurrence, neck recurrence, brain recurrence, and bone recurrence, the C-statistics of Harrell et al were 0.743 and 0.748, 0.728 and 0.703, 0.760 and 0.749, 0.779 and 0.757, 0.787 and 0.784, and 0.777 and 0.739, respectively. The calibration plots showed optimal agreement between nomogram-predicted 3-year recurrence-free survival and actual 3-year recurrence-free survival. These user-friendly nomograms can precisely predict site-specific recurrence in patients with completely resected NSCLC, based on clinicopathologic features. They may help physicians to make individual postoperative follow-up plans. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

The impact of confounder selection in propensity scores when applied to prospective cohort studies in pregnancy.

PubMed

Xu, Ronghui; Hou, Jue; Chambers, Christina D

2018-06-01

Our work was motivated by small cohort studies on the risk of birth defects in infants born to pregnant women exposed to medications. We controlled for confounding using propensity scores (PS). The extremely rare events setting renders the matching or stratification infeasible. In addition, the PS itself may be formed via different approaches to select confounders from a relatively long list of potential confounders. We carried out simulation experiments to compare different combinations of approaches: IPW or regression adjustment, with 1) including all potential confounders without selection, 2) selection based on univariate association between the candidate variable and the outcome, 3) selection based on change in effects (CIE). The simulation showed that IPW without selection leads to extremely large variances in the estimated odds ratio, which help to explain the empirical data analysis results that we had observed. Copyright © 2018 Elsevier Inc. All rights reserved.

Economic analysis for evidence-based policy-making on a national immunization program: a case of rotavirus vaccine in Thailand.

PubMed

Muangchana, Charung; Riewpaiboon, Arthorn; Jiamsiri, Suchada; Thamapornpilas, Piyanit; Warinsatian, Porpit

2012-04-16

Severe diarrhea caused by rotavirus is a health problem worldwide, including Thailand. The World Health Organization has recommended incorporating rotavirus vaccination into national immunization programs. This policy has been implemented in several countries, but not in Thailand where the mortality rate is not high. This leads to the question of whether it would be cost-effective to implement such a policy. The Thai National Vaccine Committee, through the Immunization Practice Subcommittee, has conducted an economic analysis. Their study aimed to estimate the costs of rotavirus diarrhea and of a rotavirus vaccination program, and the cost-effectiveness of such a program including budget impact analysis. The study was designed as an economic evaluation, employing modeling technique in both provider and societal perspectives. A birth cohort of Thai children in 2009 was used in the analysis, with a 5-year time horizon. Costs were composed of cost of the illness and the vaccination program. Outcomes were measured in the form of lives saved and DALYs averted. Both costs and outcomes were discounted at 3%. The study found the discounted number of deaths to be 7.02 and 20.52 for vaccinated and unvaccinated cohorts, respectively (13.5 deaths averted). Discounted DALYs were 263.33 and 826.57 for vaccinated and unvaccinated cohorts, respectively (563.24 DALYs averted). Costs of rotavirus diarrhea in a societal perspective were US$6.6 million and US$21.0 million for vaccinated and unvaccinated cohorts, respectively. At base case, the costs per additional death averted were US$5.1 million and US$5.7 for 2-dose and 3-dose vaccines, respectively, in a societal perspective. Costs per additional DALYs averted were US$128,063 and US$142,144, respectively. In a societal perspective, with a cost-effectiveness threshold at 1 GDP per capita per DALYs averted, vaccine prices per dose were US$4.98 and US$3.32 for 2-dose and 3-dose vaccines, respectively; in a provider perspective, they were US$2.90 and US$1.93. One-way and probabilistic sensitivity analyses were included. The budget required for vaccine purchase was calculated for all scenarios. Copyright © 2012 Elsevier Ltd. All rights reserved.

A mathematical prediction model incorporating molecular subtype for risk of non-sentinel lymph node metastasis in sentinel lymph node-positive breast cancer patients: a retrospective analysis and nomogram development.

PubMed

Wang, Na-Na; Yang, Zheng-Jun; Wang, Xue; Chen, Li-Xuan; Zhao, Hong-Meng; Cao, Wen-Feng; Zhang, Bin

2018-04-25

Molecular subtype of breast cancer is associated with sentinel lymph node status. We sought to establish a mathematical prediction model that included breast cancer molecular subtype for risk of positive non-sentinel lymph nodes in breast cancer patients with sentinel lymph node metastasis and further validate the model in a separate validation cohort. We reviewed the clinicopathologic data of breast cancer patients with sentinel lymph node metastasis who underwent axillary lymph node dissection between June 16, 2014 and November 16, 2017 at our hospital. Sentinel lymph node biopsy was performed and patients with pathologically proven sentinel lymph node metastasis underwent axillary lymph node dissection. Independent risks for non-sentinel lymph node metastasis were assessed in a training cohort by multivariate analysis and incorporated into a mathematical prediction model. The model was further validated in a separate validation cohort, and a nomogram was developed and evaluated for diagnostic performance in predicting the risk of non-sentinel lymph node metastasis. Moreover, we assessed the performance of five different models in predicting non-sentinel lymph node metastasis in training cohort. Totally, 495 cases were eligible for the study, including 291 patients in the training cohort and 204 in the validation cohort. Non-sentinel lymph node metastasis was observed in 33.3% (97/291) patients in the training cohort. The AUC of MSKCC, Tenon, MDA, Ljubljana, and Louisville models in training cohort were 0.7613, 0.7142, 0.7076, 0.7483, and 0.671, respectively. Multivariate regression analysis indicated that tumor size (OR = 1.439; 95% CI 1.025-2.021; P = 0.036), sentinel lymph node macro-metastasis versus micro-metastasis (OR = 5.063; 95% CI 1.111-23.074; P = 0.036), the number of positive sentinel lymph nodes (OR = 2.583, 95% CI 1.714-3.892; P < 0.001), and the number of negative sentinel lymph nodes (OR = 0.686, 95% CI 0.575-0.817; P < 0.001) were independent statistically significant predictors of non-sentinel lymph node metastasis. Furthermore, luminal B (OR = 3.311, 95% CI 1.593-6.884; P = 0.001) and HER2 overexpression (OR = 4.308, 95% CI 1.097-16.912; P = 0.036) were independent and statistically significant predictor of non-sentinel lymph node metastasis versus luminal A. A regression model based on the results of multivariate analysis was established to predict the risk of non-sentinel lymph node metastasis, which had an AUC of 0.8188. The model was validated in the validation cohort and showed excellent diagnostic performance. The mathematical prediction model that incorporates five variables including breast cancer molecular subtype demonstrates excellent diagnostic performance in assessing the risk of non-sentinel lymph node metastasis in sentinel lymph node-positive patients. The prediction model could be of help surgeons in evaluating the risk of non-sentinel lymph node involvement for breast cancer patients; however, the model requires further validation in prospective studies.

Electronic health record analysis via deep poisson factor models

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

Henao, Ricardo; Lu, James T.; Lucas, Joseph E.

Electronic Health Record (EHR) phenotyping utilizes patient data captured through normal medical practice, to identify features that may represent computational medical phenotypes. These features may be used to identify at-risk patients and improve prediction of patient morbidity and mortality. We present a novel deep multi-modality architecture for EHR analysis (applicable to joint analysis of multiple forms of EHR data), based on Poisson Factor Analysis (PFA) modules. Each modality, composed of observed counts, is represented as a Poisson distribution, parameterized in terms of hidden binary units. In-formation from different modalities is shared via a deep hierarchy of common hidden units. Activationmore » of these binary units occurs with probability characterized as Bernoulli-Poisson link functions, instead of more traditional logistic link functions. In addition, we demon-strate that PFA modules can be adapted to discriminative modalities. To compute model parameters, we derive efficient Markov Chain Monte Carlo (MCMC) inference that scales efficiently, with significant computational gains when compared to related models based on logistic link functions. To explore the utility of these models, we apply them to a subset of patients from the Duke-Durham patient cohort. We identified a cohort of over 12,000 patients with Type 2 Diabetes Mellitus (T2DM) based on diagnosis codes and laboratory tests out of our patient population of over 240,000. Examining the common hidden units uniting the PFA modules, we identify patient features that represent medical concepts. Experiments indicate that our learned features are better able to predict mortality and morbidity than clinical features identified previously in a large-scale clinical trial.« less

Electronic health record analysis via deep poisson factor models

DOE PAGES

Henao, Ricardo; Lu, James T.; Lucas, Joseph E.; ...

2016-01-01

Electronic Health Record (EHR) phenotyping utilizes patient data captured through normal medical practice, to identify features that may represent computational medical phenotypes. These features may be used to identify at-risk patients and improve prediction of patient morbidity and mortality. We present a novel deep multi-modality architecture for EHR analysis (applicable to joint analysis of multiple forms of EHR data), based on Poisson Factor Analysis (PFA) modules. Each modality, composed of observed counts, is represented as a Poisson distribution, parameterized in terms of hidden binary units. In-formation from different modalities is shared via a deep hierarchy of common hidden units. Activationmore » of these binary units occurs with probability characterized as Bernoulli-Poisson link functions, instead of more traditional logistic link functions. In addition, we demon-strate that PFA modules can be adapted to discriminative modalities. To compute model parameters, we derive efficient Markov Chain Monte Carlo (MCMC) inference that scales efficiently, with significant computational gains when compared to related models based on logistic link functions. To explore the utility of these models, we apply them to a subset of patients from the Duke-Durham patient cohort. We identified a cohort of over 12,000 patients with Type 2 Diabetes Mellitus (T2DM) based on diagnosis codes and laboratory tests out of our patient population of over 240,000. Examining the common hidden units uniting the PFA modules, we identify patient features that represent medical concepts. Experiments indicate that our learned features are better able to predict mortality and morbidity than clinical features identified previously in a large-scale clinical trial.« less

Influence of arterial hypertension, type 2 diabetes and cardiovascular risk factors on ALS outcome: a population-based study.

PubMed

Moglia, Cristina; Calvo, Andrea; Canosa, Antonio; Bertuzzo, Davide; Cugnasco, Paolo; Solero, Luca; Grassano, Maurizio; Bersano, Enrica; Cammarosano, Stefania; Manera, Umberto; Pisano, Fabrizio; Mazzini, Letizia; Dalla Vecchia, Laura A; Mora, Gabriele; Chiò, Adriano

2017-11-01

To assess the prognostic influence of pre-morbid type 2 diabetes mellitus, arterial hypertension and cardiovascular (CV) risk profile on ALS phenotype and outcome in a population-based cohort of Italian patients. A total of 650 ALS patients from the Piemonte/Valle d'Aosta Register for ALS, incident in the 2007-2011 period, were recruited. Information about premorbid presence of type 2 diabetes mellitus, arterial hypertension was collected at the time of diagnosis. Patients' CV risk profile was calculated according to the Joint British Societies' guidelines on prevention of cardiovascular disease in clinical practice (JBS2). At the univariate analysis, the presence of pre-morbid arterial hypertension was associated with a higher age at onset of ALS and a shorter survival, and patients with a high CV risk profile had a worse prognosis than those with a low CV risk profile. The Cox multivariable analysis did not confirm such findings. Type 2 diabetes mellitus did not modify either the phenotype or the prognosis of ALS patients. This study performed on a large population-based cohort of ALS patients has demonstrated that arterial hypertension, type 2 diabetes and CV risk factors, calculated using the Framingham equation, do not influence ALS phenotype and prognosis.

Situating Computer Simulation Professional Development: Does It Promote Inquiry-Based Simulation Use?

ERIC Educational Resources Information Center

Gonczi, Amanda L.; Maeng, Jennifer L.; Bell, Randy L.; Whitworth, Brooke A.

2016-01-01

This mixed-methods study sought to identify professional development implementation variables that may influence participant (a) adoption of simulations, and (b) use for inquiry-based science instruction. Two groups (Cohort 1, N = 52; Cohort 2, N = 104) received different professional development. Cohort 1 was focused on Web site use mechanics.…

A Molecular Host Response Assay to Discriminate Between Sepsis and Infection-Negative Systemic Inflammation in Critically Ill Patients: Discovery and Validation in Independent Cohorts

PubMed Central

McHugh, Leo; Seldon, Therese A.; Brandon, Roslyn A.; Kirk, James T.; Rapisarda, Antony; Sutherland, Allison J.; Presneill, Jeffrey J.; Venter, Deon J.; Lipman, Jeffrey; Thomas, Mervyn R.; Klein Klouwenberg, Peter M. C.; van Vught, Lonneke; Scicluna, Brendon; Bonten, Marc; Cremer, Olaf L.; Schultz, Marcus J.; van der Poll, Tom; Yager, Thomas D.; Brandon, Richard B.

2015-01-01

Background Systemic inflammation is a whole body reaction having an infection-positive (i.e., sepsis) or infection-negative origin. It is important to distinguish between these two etiologies early and accurately because this has significant therapeutic implications for critically ill patients. We hypothesized that a molecular classifier based on peripheral blood RNAs could be discovered that would (1) determine which patients with systemic inflammation had sepsis, (2) be robust across independent patient cohorts, (3) be insensitive to disease severity, and (4) provide diagnostic utility. The goal of this study was to identify and validate such a molecular classifier. Methods and Findings We conducted an observational, non-interventional study of adult patients recruited from tertiary intensive care units (ICUs). Biomarker discovery utilized an Australian cohort (n = 105) consisting of 74 cases (sepsis patients) and 31 controls (post-surgical patients with infection-negative systemic inflammation) recruited at five tertiary care settings in Brisbane, Australia, from June 3, 2008, to December 22, 2011. A four-gene classifier combining CEACAM4, LAMP1, PLA2G7, and PLAC8 RNA biomarkers was identified. This classifier, designated SeptiCyte Lab, was validated using reverse transcription quantitative PCR and receiver operating characteristic (ROC) curve analysis in five cohorts (n = 345) from the Netherlands. Patients for validation were selected from the Molecular Diagnosis and Risk Stratification of Sepsis study (ClinicalTrials.gov, NCT01905033), which recruited ICU patients from the Academic Medical Center in Amsterdam and the University Medical Center Utrecht. Patients recruited from November 30, 2012, to August 5, 2013, were eligible for inclusion in the present study. Validation cohort 1 (n = 59) consisted entirely of unambiguous cases and controls; SeptiCyte Lab gave an area under curve (AUC) of 0.95 (95% CI 0.91–1.00) in this cohort. ROC curve analysis of an independent, more heterogeneous group of patients (validation cohorts 2–5; 249 patients after excluding 37 patients with an infection likelihood of “possible”) gave an AUC of 0.89 (95% CI 0.85–0.93). Disease severity, as measured by Sequential Organ Failure Assessment (SOFA) score or Acute Physiology and Chronic Health Evaluation (APACHE) IV score, was not a significant confounding variable. The diagnostic utility of SeptiCyte Lab was evaluated by comparison to various clinical and laboratory parameters available to a clinician within 24 h of ICU admission. SeptiCyte Lab was significantly better at differentiating cases from controls than all tested parameters, both singly and in various logistic combinations, and more than halved the diagnostic error rate compared to procalcitonin in all tested cohorts and cohort combinations. Limitations of this study relate to (1) cohort compositions that do not perfectly reflect the composition of the intended use population, (2) potential biases that could be introduced as a result of the current lack of a gold standard for diagnosing sepsis, and (3) lack of a complete, unbiased comparison to C-reactive protein. Conclusions SeptiCyte Lab is a rapid molecular assay that may be clinically useful in managing ICU patients with systemic inflammation. Further study in population-based cohorts is needed to validate this assay for clinical use. PMID:26645559

An Agent-Based Modeling Template for a Cohort of Veterans with Diabetic Retinopathy.

PubMed

Day, Theodore Eugene; Ravi, Nathan; Xian, Hong; Brugh, Ann

2013-01-01

Agent-based models are valuable for examining systems where large numbers of discrete individuals interact with each other, or with some environment. Diabetic Veterans seeking eye care at a Veterans Administration hospital represent one such cohort. The objective of this study was to develop an agent-based template to be used as a model for a patient with diabetic retinopathy (DR). This template may be replicated arbitrarily many times in order to generate a large cohort which is representative of a real-world population, upon which in-silico experimentation may be conducted. Agent-based template development was performed in java-based computer simulation suite AnyLogic Professional 6.6. The model was informed by medical data abstracted from 535 patient records representing a retrospective cohort of current patients of the VA St. Louis Healthcare System Eye clinic. Logistic regression was performed to determine the predictors associated with advancing stages of DR. Predicted probabilities obtained from logistic regression were used to generate the stage of DR in the simulated cohort. The simulated cohort of DR patients exhibited no significant deviation from the test population of real-world patients in proportion of stage of DR, duration of diabetes mellitus (DM), or the other abstracted predictors. Simulated patients after 10 years were significantly more likely to exhibit proliferative DR (P<0.001). Agent-based modeling is an emerging platform, capable of simulating large cohorts of individuals based on manageable data abstraction efforts. The modeling method described may be useful in simulating many different conditions where course of disease is described in categorical stages.

Group in-course assessment promotes cooperative learning and increases performance.

PubMed

Pratten, Margaret K; Merrick, Deborah; Burr, Steven A

2014-01-01

The authors describe and evaluate a method to motivate medical students to maximize the effectiveness of dissection opportunities by using In-Course-Assessments (ICAs) to encourage teamwork. A student's final mark was derived by combining the group dissection mark, group mark for questions, and their individual question mark. An analysis of the impact of the ICA was performed by comparing end of module practical summative marks in student cohorts who had, or had not, participated in the ICAs. Summative marks were compared by two-way ANOVA followed by Dunnets test, or by repeated measures ANOVA, as appropriate. A cohort of medical students was selected that had experienced both practical classes without (year one) and with the new ICA structure (year two). Comparison of summative year one and year two marks illustrated an increased improvement in year two performance in this cohort. A significant increase was also noted when comparing this cohort with five preceding year two cohorts who had not experienced the ICAs (P <0.0001). To ensure that variation in the practical summative examination was not impacting on the data, a comparison was made between three cohorts who had performed the same summative examination. Results show that students who had undertook weekly ICAs showed significantly improved summative marks, compared with those who did not (P <0.0001). This approach to ICA promotes engagement with learning resources in an active, team-based, cooperative learning environment. © 2013 American Association of Anatomists.

Gene network inherent in genomic big data improves the accuracy of prognostic prediction for cancer patients.

PubMed

Kim, Yun Hak; Jeong, Dae Cheon; Pak, Kyoungjune; Goh, Tae Sik; Lee, Chi-Seung; Han, Myoung-Eun; Kim, Ji-Young; Liangwen, Liu; Kim, Chi Dae; Jang, Jeon Yeob; Cha, Wonjae; Oh, Sae-Ock

2017-09-29

Accurate prediction of prognosis is critical for therapeutic decisions regarding cancer patients. Many previously developed prognostic scoring systems have limitations in reflecting recent progress in the field of cancer biology such as microarray, next-generation sequencing, and signaling pathways. To develop a new prognostic scoring system for cancer patients, we used mRNA expression and clinical data in various independent breast cancer cohorts (n=1214) from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO). A new prognostic score that reflects gene network inherent in genomic big data was calculated using Network-Regularized high-dimensional Cox-regression (Net-score). We compared its discriminatory power with those of two previously used statistical methods: stepwise variable selection via univariate Cox regression (Uni-score) and Cox regression via Elastic net (Enet-score). The Net scoring system showed better discriminatory power in prediction of disease-specific survival (DSS) than other statistical methods (p=0 in METABRIC training cohort, p=0.000331, 4.58e-06 in two METABRIC validation cohorts) when accuracy was examined by log-rank test. Notably, comparison of C-index and AUC values in receiver operating characteristic analysis at 5 years showed fewer differences between training and validation cohorts with the Net scoring system than other statistical methods, suggesting minimal overfitting. The Net-based scoring system also successfully predicted prognosis in various independent GEO cohorts with high discriminatory power. In conclusion, the Net-based scoring system showed better discriminative power than previous statistical methods in prognostic prediction for breast cancer patients. This new system will mark a new era in prognosis prediction for cancer patients.

Is schizophrenia associated with an increased risk of chronic kidney disease? A nationwide matched-cohort study.

PubMed

Tzeng, Nian-Sheng; Hsu, Yung-Ho; Ho, Shinn-Ying; Kuo, Yu-Ching; Lee, Hua-Chin; Yin, Yun-Ju; Chen, Hong-An; Chen, Wen-Liang; Chu, William Cheng-Chung; Huang, Hui-Ling

2015-01-27

The impact of schizophrenia on vital diseases, such as chronic kidney disease (CKD), has not as yet been verified. This study aims to establish whether there is an association between schizophrenia and CKD. A nationwide matched cohort study. Taiwan's National Health Insurance Research Database. A total of 2338 patients with schizophrenia, and 7014 controls without schizophrenia (1:3), matched cohort for sex, age group, geography, urbanisation and monthly income, between 1 January 2003 and 31 December 2007, based on the International Classifications of Disease Ninth Edition (ICD-9), Clinical Modification codes. After making adjustments for confounding risk factors, a Cox proportional hazards model was used to compare the risk of developing CKD during a 3-year follow-up period from the index date. Of the 2338-subject case cohort, 163 (6.97%) developed a CKD, as did 365 (5.20%) of the 7014 control participants. Cox proportional hazards regression analysis revealed that patients with schizophrenia were more likely to develop CKD (HR=1.36, 95% CI 1.13 to 1.63; p<0.001). After adjusting for gender, age group, hypertension, diabetes mellitus, hyperlipidaemia, heart disease and non-steroid anti-inflammatory drugs (NSAIDs) usage, the HR for patients with schizophrenia was 1.25 (95% CI 1.04 to 1.50; p<0.05). Neither typical nor atypical antipsychotics was associated an increased risk of CKD in patients with schizophrenia. The findings from this population-based retrospective cohort study suggest that schizophrenia is associated with a 25% increase in the risk of developing CKD within only a 3-year follow-up period. 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.

What's in a Name? The Incorrect Use of Case Series as a Study Design Label in Studies Involving Dogs and Cats.

PubMed

Sargeant, J M; O'Connor, A M; Cullen, J N; Makielski, K M; Jones-Bitton, A

2017-07-01

Study design labels are used to identify relevant literature to address specific clinical and research questions and to aid in evaluating the evidentiary value of research. Evidence from the human healthcare literature indicates that the label "case series" may be used inconsistently and inappropriately. Our primary objective was to determine the proportion of studies in the canine and feline veterinary literature labeled as case series that actually corresponded to descriptive cohort studies, population-based cohort studies, or other study designs. Our secondary objective was to identify the proportion of case series in which potentially inappropriate inferential statements were made. Descriptive evaluation of published literature. One-hundred published studies (from 19 journals) labeled as case series. Studies were identified by a structured literature search, with random selection of 100 studies from the relevant citations. Two reviewers independently characterized each study, with disagreements resolved by consensus. Of the 100 studies, 16 were case series. The remaining studies were descriptive cohort studies (35), population-based cohort studies (36), or other observational or experimental study designs (13). Almost half (48.8%) of the case series or descriptive cohort studies, with no control group and no formal statistical analysis, included inferential statements about the efficacy of treatment or statistical significance of potential risk factors. Authors, peer-reviewers, and editors should carefully consider the design elements of a study to accurately identify and label the study design. Doing so will facilitate an understanding of the evidentiary value of the results. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Gene network inherent in genomic big data improves the accuracy of prognostic prediction for cancer patients

PubMed Central

Kim, Yun Hak; Jeong, Dae Cheon; Pak, Kyoungjune; Goh, Tae Sik; Lee, Chi-Seung; Han, Myoung-Eun; Kim, Ji-Young; Liangwen, Liu; Kim, Chi Dae; Jang, Jeon Yeob; Cha, Wonjae; Oh, Sae-Ock

2017-01-01

Accurate prediction of prognosis is critical for therapeutic decisions regarding cancer patients. Many previously developed prognostic scoring systems have limitations in reflecting recent progress in the field of cancer biology such as microarray, next-generation sequencing, and signaling pathways. To develop a new prognostic scoring system for cancer patients, we used mRNA expression and clinical data in various independent breast cancer cohorts (n=1214) from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO). A new prognostic score that reflects gene network inherent in genomic big data was calculated using Network-Regularized high-dimensional Cox-regression (Net-score). We compared its discriminatory power with those of two previously used statistical methods: stepwise variable selection via univariate Cox regression (Uni-score) and Cox regression via Elastic net (Enet-score). The Net scoring system showed better discriminatory power in prediction of disease-specific survival (DSS) than other statistical methods (p=0 in METABRIC training cohort, p=0.000331, 4.58e-06 in two METABRIC validation cohorts) when accuracy was examined by log-rank test. Notably, comparison of C-index and AUC values in receiver operating characteristic analysis at 5 years showed fewer differences between training and validation cohorts with the Net scoring system than other statistical methods, suggesting minimal overfitting. The Net-based scoring system also successfully predicted prognosis in various independent GEO cohorts with high discriminatory power. In conclusion, the Net-based scoring system showed better discriminative power than previous statistical methods in prognostic prediction for breast cancer patients. This new system will mark a new era in prognosis prediction for cancer patients. PMID:29100405

Novel Anthropometry Based on 3D-Bodyscans Applied to a Large Population Based Cohort

PubMed Central

Löffler-Wirth, Henry; Willscher, Edith; Ahnert, Peter; Wirkner, Kerstin; Engel, Christoph; Loeffler, Markus; Binder, Hans

2016-01-01

Three-dimensional (3D) whole body scanners are increasingly used as precise measuring tools for the rapid quantification of anthropometric measures in epidemiological studies. We analyzed 3D whole body scanning data of nearly 10,000 participants of a cohort collected from the adult population of Leipzig, one of the largest cities in Eastern Germany. We present a novel approach for the systematic analysis of this data which aims at identifying distinguishable clusters of body shapes called body types. In the first step, our method aggregates body measures provided by the scanner into meta-measures, each representing one relevant dimension of the body shape. In a next step, we stratified the cohort into body types and assessed their stability and dependence on the size of the underlying cohort. Using self-organizing maps (SOM) we identified thirteen robust meta-measures and fifteen body types comprising between 1 and 18 percent of the total cohort size. Thirteen of them are virtually gender specific (six for women and seven for men) and thus reflect most abundant body shapes of women and men. Two body types include both women and men, and describe androgynous body shapes that lack typical gender specific features. The body types disentangle a large variability of body shapes enabling distinctions which go beyond the traditional indices such as body mass index, the waist-to-height ratio, the waist-to-hip ratio and the mortality-hazard ABSI-index. In a next step, we will link the identified body types with disease predispositions to study how size and shape of the human body impact health and disease. PMID:27467550

Is an unfavourable cardiovascular risk profile a risk factor for vasomotor menopausal symptoms? Results of a population-based cohort study.

PubMed

van den Berg, M J; Herber-Gast, G C M; van der Schouw, Y T

2015-08-01

Evidence suggests an association between vasomotor menopausal symptoms (VMSs), i.e. hot flushes and night sweats, and cardiovascular disease. However, the causal pathway is unclear. We investigated whether an unfavourable cardiovascular risk profile is a risk factor for VMS later in life. Retrospective cohort study. Women aged 50-70 from the general population. The Prospect-European Prospective Investigation into Cancer and Nutrition (Prospect-EPIC) cohort is a population-based cohort of women who enrolled between 1993 and 1997. Follow-up questionnaires were sent at 5-year intervals for 15 years. Women who returned the third questionnaire, answered questions regarding lifetime VMS and did not report VMS prior to baseline were included in this study (n = 1295). At baseline, the Framingham Risk Score (FRS) was determined. We used logistic regression analysis to calculate odds ratios (ORs) for the association between baseline FRS and incident VMS. Incident VMS. At baseline (mean age ± standard deviation, 52.2 ± 3.6 years), 21.2% had a FRS > 10%. During follow-up, 40.2% of women reported the onset of VMS. Adjusted for body mass index, physical activity, education and alcohol consumption, each point increase in FRS was associated with a decreased incidence of VMS [OR, 0.94 (95% CI, 0.91-0.97)]. Additional adjustment for menopausal status attenuated the OR to null [OR, 0.98 (95% CI, 0.95-1.01)]. None of the separate FRS variables were associated with VMS after adjustment for age. In our cohort, an unfavourable cardiovascular risk profile was not associated with VMS, and therefore we found no evidence for the involvement of a vascular mechanism in the etiology of VMS. © 2014 Royal College of Obstetricians and Gynaecologists.

COMPUTATIONAL ANALYSIS OF SWALLOWING MECHANICS UNDERLYING IMPAIRED EPIGLOTTIC INVERSION

PubMed Central

Pearson, William G.; Taylor, Brandon K; Blair, Julie; Martin-Harris, Bonnie

2015-01-01

Objective Determine swallowing mechanics associated with the first and second epiglottic movements, that is, movement to horizontal and full inversion respectively, in order to provide a clinical interpretation of impaired epiglottic function. Study Design Retrospective cohort study. Methods A heterogeneous cohort of patients with swallowing difficulties was identified (n=92). Two speech-language pathologists reviewed 5ml thin and 5ml pudding videofluoroscopic swallow studies per subject, and assigned epiglottic component scores of 0=complete inversion, 1=partial inversion, and 2=no inversion forming three groups of videos for comparison. Coordinates mapping minimum and maximum excursion of the hyoid, pharynx, larynx, and tongue base during pharyngeal swallowing were recorded using ImageJ software. A canonical variate analysis with post-hoc discriminant function analysis of coordinates was performed using MorphoJ software to evaluate mechanical differences between groups. Eigenvectors characterizing swallowing mechanics underlying impaired epiglottic movements were visualized. Results Nineteen of 184 video-swallows were rejected for poor quality (n=165). A Goodman-Kruskal index of predictive association showed no correlation between epiglottic component scores and etiologies of dysphagia (λ=.04). A two-way analysis of variance by epiglottic component scores showed no significant interaction effects between sex and age (f=1.4, p=.25). Discriminant function analysis demonstrated statistically significant mechanical differences between epiglottic component scores: 1&2, representing the first epiglottic movement (Mahalanobis distance=1.13, p=.0007); and, 0&1, representing the second epiglottic movement (Mahalanobis distance=0.83, p=.003). Eigenvectors indicate that laryngeal elevation and tongue base retraction underlie both epiglottic movements. Conclusion Results suggest that reduced tongue base retraction and laryngeal elevation underlie impaired first and second epiglottic movements. The styloglossus, hyoglossus and long pharyngeal muscles are implicated as targets for rehabilitation in dysphagic patients with impaired epiglottic inversion. PMID:27426940

Time Spent Walking and Risk of Diabetes in Japanese Adults: The Japan Public Health Center-Based Prospective Diabetes Study

PubMed Central

Kabeya, Yusuke; Goto, Atsushi; Kato, Masayuki; Matsushita, Yumi; Takahashi, Yoshihiko; Isogawa, Akihiro; Inoue, Manami; Mizoue, Tetsuya; Tsugane, Shoichiro; Kadowaki, Takashi; Noda, Mitsuhiko

2016-01-01

Background The association between time spent walking and risk of diabetes was investigated in a Japanese population-based cohort. Methods Data from the Japan Public Health Center-based Prospective Diabetes cohort were analyzed. The surveys of diabetes were performed at baseline and at the 5-year follow-up. Time spent walking per day was assessed using a self-reported questionnaire (<30 minutes, 30 minutes to <1 hour, 1 to <2 hours, or ≥2 hours). A cross-sectional analysis was performed among 26 488 adults in the baseline survey. Logistic regression was used to examine the association between time spent walking and the presence of unrecognized diabetes. We then performed a longitudinal analysis that was restricted to 11 101 non-diabetic adults who participated in both the baseline and 5-year surveys. The association between time spent walking and the incidence of diabetes during the 5 years was examined. Results In the cross-sectional analysis, 1058 participants had unrecognized diabetes. Those with time spent walking of <30 minutes per day had increased odds of having diabetes in relation to those with time spent walking of ≥2 hours (adjusted odds ratio [OR] 1.23; 95% CI, 1.02–1.48). In the longitudinal analysis, 612 participants developed diabetes during the 5 years of follow-up. However, a significant association between time spent walking and the incidence of diabetes was not observed. Conclusions Increased risk of diabetes was implied in those with time spent walking of <30 minutes per day, although the longitudinal analysis failed to show a significant result. PMID:26725285

Vaccines are not associated with autism: an evidence-based meta-analysis of case-control and cohort studies.

PubMed

Taylor, Luke E; Swerdfeger, Amy L; Eslick, Guy D

2014-06-17

There has been enormous debate regarding the possibility of a link between childhood vaccinations and the subsequent development of autism. This has in recent times become a major public health issue with vaccine preventable diseases increasing in the community due to the fear of a 'link' between vaccinations and autism. We performed a meta-analysis to summarise available evidence from case-control and cohort studies on this topic (MEDLINE, PubMed, EMBASE, Google Scholar up to April, 2014). Eligible studies assessed the relationship between vaccine administration and the subsequent development of autism or autism spectrum disorders (ASD). Two reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus with another author. Five cohort studies involving 1,256,407 children, and five case-control studies involving 9,920 children were included in this analysis. The cohort data revealed no relationship between vaccination and autism (OR: 0.99; 95% CI: 0.92 to 1.06) or ASD (OR: 0.91; 95% CI: 0.68 to 1.20), nor was there a relationship between autism and MMR (OR: 0.84; 95% CI: 0.70 to 1.01), or thimerosal (OR: 1.00; 95% CI: 0.77 to 1.31), or mercury (Hg) (OR: 1.00; 95% CI: 0.93 to 1.07). Similarly the case-control data found no evidence for increased risk of developing autism or ASD following MMR, Hg, or thimerosal exposure when grouped by condition (OR: 0.90, 95% CI: 0.83 to 0.98; p=0.02) or grouped by exposure type (OR: 0.85, 95% CI: 0.76 to 0.95; p=0.01). Findings of this meta-analysis suggest that vaccinations are not associated with the development of autism or autism spectrum disorder. Furthermore, the components of the vaccines (thimerosal or mercury) or multiple vaccines (MMR) are not associated with the development of autism or autism spectrum disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

Conversion-to-open in laparoscopic appendectomy: A cohort analysis of risk factors and outcomes.

PubMed

Finnerty, Brendan M; Wu, Xian; Giambrone, Gregory P; Gaber-Baylis, Licia K; Zabih, Ramin; Bhat, Akshay; Zarnegar, Rasa; Pomp, Alfons; Fleischut, Peter; Afaneh, Cheguevara

2017-04-01

Identifying risk factors for conversion from laparoscopic to open appendectomy could select patients who may benefit from primary open appendectomy. We aimed to develop a predictive scoring model for conversion from laparoscopic to open based on pre-operative patient characteristics. A retrospective review of the State Inpatient Database (2007-2011) was performed using derivation (N = 71,617) and validation (N = 143,235) cohorts of adults ≥ 18 years with acute appendicitis treated by laparoscopic-only (LA), conversion from laparoscopic to open (CA), or primary open (OA) appendectomy. Pre-operative variables independently associated with CA were identified and reported as odds ratios (OR) with 95% confidence intervals (CI). A weighted integer-based scoring model to predict CA was designed based on pre-operative variable ORs, and complications between operative subgroups were compared. Independent predictors of CA in the derivation cohort were age ≥40 (OR 1.67; CI 1.55-1.80), male sex (OR 1.25; CI 1.17-1.34), black race (OR 1.46; CI 1.28-1.66), diabetes (OR 1.47; CI 1.31-1.65), obesity (OR 1.56; CI 1.40-1.74), and acute appendicitis with abscess or peritonitis (OR 7.00; CI 6.51-7.53). In the validation cohort, the CA predictive scoring model had an optimal cutoff score of 4 (range 0-9). The risk of conversion-to-open was ≤5% for a score <4, compared to 10-25% for a score ≥4. On composite outcomes analysis controlling for all pre-operative variables, CA had a higher likelihood of infectious/inflammatory (OR 1.44; CI 1.31-1.58), hematologic (OR 1.31; CI 1.17-1.46), and renal (OR 1.22; CI 1.06-1.39) complications compared to OA. Additionally, CA had a higher likelihood of infectious/inflammatory, respiratory, cardiovascular, hematologic, and renal complications compared to LA. CA patients have an unfavorable complication profile compared to OA. The predictors identified in this scoring model could help select for patients who may benefit from primary open appendectomy. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Methodological challenges in measuring vaccine effectiveness using population cohorts in low resource settings.

PubMed

King, C; Beard, J; Crampin, A C; Costello, A; Mwansambo, C; Cunliffe, N A; Heyderman, R S; French, N; Bar-Zeev, N

2015-09-11

Post-licensure real world evaluation of vaccine implementation is important for establishing evidence of vaccine effectiveness (VE) and programme impact, including indirect effects. Large cohort studies offer an important epidemiological approach for evaluating VE, but have inherent methodological challenges. Since March 2012, we have conducted an open prospective cohort study in two sites in rural Malawi to evaluate the post-introduction effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against all-cause post-neonatal infant mortality and monovalent rotavirus vaccine (RV1) against diarrhoea-related post-neonatal infant mortality. Our study sites cover a population of 500,000, with a baseline post-neonatal infant mortality of 25 per 1000 live births. We conducted a methodological review of cohort studies for vaccine effectiveness in a developing country setting, applied to our study context. Based on published literature, we outline key considerations when defining the denominator (study population), exposure (vaccination status) and outcome ascertainment (mortality and cause of death) of such studies. We assess various definitions in these three domains, in terms of their impact on power, effect size and potential biases and their direction, using our cohort study for illustration. Based on this iterative process, we discuss the pros and cons of our final per-protocol analysis plan. Since no single set of definitions or analytical approach accounts for all possible biases, we propose sensitivity analyses to interrogate our assumptions and methodological decisions. In the poorest regions of the world where routine vital birth and death surveillance are frequently unavailable and the burden of disease and death is greatest We conclude that provided the balance between definitions and their overall assumed impact on estimated VE are acknowledged, such large scale real-world cohort studies can provide crucial information to policymakers by providing robust and compelling evidence of total benefits of newly introduced vaccines on reducing child mortality. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Methodological challenges in measuring vaccine effectiveness using population cohorts in low resource settings

PubMed Central

King, C.; Beard, J.; Crampin, A.C.; Costello, A.; Mwansambo, C.; Cunliffe, N.A.; Heyderman, R.S.; French, N.; Bar-Zeev, N.

2015-01-01

Post-licensure real world evaluation of vaccine implementation is important for establishing evidence of vaccine effectiveness (VE) and programme impact, including indirect effects. Large cohort studies offer an important epidemiological approach for evaluating VE, but have inherent methodological challenges. Since March 2012, we have conducted an open prospective cohort study in two sites in rural Malawi to evaluate the post-introduction effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) against all-cause post-neonatal infant mortality and monovalent rotavirus vaccine (RV1) against diarrhoea-related post-neonatal infant mortality. Our study sites cover a population of 500,000, with a baseline post-neonatal infant mortality of 25 per 1000 live births. We conducted a methodological review of cohort studies for vaccine effectiveness in a developing country setting, applied to our study context. Based on published literature, we outline key considerations when defining the denominator (study population), exposure (vaccination status) and outcome ascertainment (mortality and cause of death) of such studies. We assess various definitions in these three domains, in terms of their impact on power, effect size and potential biases and their direction, using our cohort study for illustration. Based on this iterative process, we discuss the pros and cons of our final per-protocol analysis plan. Since no single set of definitions or analytical approach accounts for all possible biases, we propose sensitivity analyses to interrogate our assumptions and methodological decisions. In the poorest regions of the world where routine vital birth and death surveillance are frequently unavailable and the burden of disease and death is greatest We conclude that provided the balance between definitions and their overall assumed impact on estimated VE are acknowledged, such large scale real-world cohort studies can provide crucial information to policymakers by providing robust and compelling evidence of total benefits of newly introduced vaccines on reducing child mortality. PMID:26235370

Risk of infective endocarditis in patients with systemic lupus erythematosus in Taiwan: a nationwide population-based study.

PubMed

Chang, Y S; Chang, C C; Chen, Y H; Chen, W S; Chen, J H

2017-10-01

Objectives Patients with systemic lupus erythematosus are considered vulnerable to infective endocarditis and prophylactic antibiotics are recommended before an invasive dental procedure. However, the evidence is insufficient. This nationwide population-based study evaluated the risk and related factors of infective endocarditis in systemic lupus erythematosus. Methods We identified 12,102 systemic lupus erythematosus patients from the National Health Insurance research-oriented database, and compared the incidence rate of infective endocarditis with that among 48,408 non-systemic lupus erythematosus controls. A Cox multivariable proportional hazards model was employed to evaluate the risk of infective endocarditis in the systemic lupus erythematosus cohort. Results After a mean follow-up of more than six years, the systemic lupus erythematosus cohort had a significantly higher incidence rate of infective endocarditis (42.58 vs 4.32 per 100,000 person-years, incidence rate ratio = 9.86, p < 0.001) than that of the control cohort. By contrast, the older systemic lupus erythematosus cohort had lower risk (adjusted hazard ratio 11.64) than that of the younger-than-60-years systemic lupus erythematosus cohort (adjusted hazard ratio 15.82). Cox multivariate proportional hazards analysis revealed heart disease (hazard ratio = 5.71, p < 0.001), chronic kidney disease (hazard ratio = 2.98, p = 0.034), receiving a dental procedure within 30 days (hazard ratio = 36.80, p < 0.001), and intravenous steroid therapy within 30 days (hazard ratio = 39.59, p < 0.001) were independent risk factors for infective endocarditis in systemic lupus erythematosus patients. Conclusions A higher risk of infective endocarditis was observed in systemic lupus erythematosus patients. Risk factors for infective endocarditis in the systemic lupus erythematosus cohort included heart disease, chronic kidney disease, steroid pulse therapy within 30 days, and a recent invasive dental procedure within 30 days.

Identification of men with low-risk biopsy-confirmed prostate cancer as candidates for active surveillance.

PubMed

Lin, Daniel W; Crawford, E David; Keane, Thomas; Evans, Brent; Reid, Julia; Rajamani, Saradha; Brown, Krystal; Gutin, Alexander; Tward, Jonathan; Scardino, Peter; Brawer, Michael; Stone, Steven; Cuzick, Jack

2018-06-01

A combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS. The score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort. In the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 × 10 -5 ). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively). The CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS. Copyright © 2018 Elsevier Inc. All rights reserved.

Biostatistical analysis of mortality data for cohorts of cancer patients.

PubMed Central

Pauling, L

1989-01-01

The Hardin Jones principle states that for a homogeneous cohort of cancer patients the logarithm of the fraction surviving at time t has a constant slope. With use of this principle, the survival times of the members of a heterogeneous cohort can be analyzed to divide the cohort into subcohorts with different mortality rate constants. Probable values of the additional survival time can be estimated for members surviving at the closing date of a clinical trial, permitting them to be included in the biostatistical analysis of the results of the trial in a more significant way than through Kaplan-Meier renormalization. PMID:2726729

Analysis of urban-rural population dynamics for China.

PubMed

Shen, J

1991-12-01

The population dynamics of China are presented in a multiregional demographic model using regional estimates or mortality and migration based on the 1% population sample survey in 1987. An open ended population account is generated for period cohort a, gender g of region i (urban) and j (rural) using population, birth, death, and migration. Demographic rates and equations for flows of nonsurviving migrants of period cohort a of gender g are estimated using the forward demographic rate definition. Out-migration rates for period cohort a of gender g are defined by migration flow divided by the initial population. The death rate for period cohort A1 and A are estimated using a single region method. Death and migration rates are simultaneously estimated with an iterative procedure. The population accounts estimates and demographic rates are provided for the period ending 1986-87 for male births, males in period cohorts 10 and 20, female births, and females in period cohorts 10 and 20. The urban and rural population projection model is based on the population accounts concept and assumes fixed rates of mortality, migration, and normal fertility for the base year 1987. The results of this projection are a population of 1090 million that will grow to 1304 million in 2000, 1720 million in 2050, and 1791 million in 2087. Urban population will expand from 44.2% in 1988 to 46.6% in 2000, and 54.7% in 2087. The labor population of males 18-65 years and females 18-60 years will increase from 58.8% in 1988 to 59.7% in 2000 and decline to 58.4% by 2087. The old age population of males 65 years and females 60 years will increase from 6.5% in 1988 to 7.9% in 2000, and 16.3% in 2087. The mean age increased from 28.3 years in 1988 to 37 in 2087. Urban population may be underprojected; migration problems are recognized. Fertility also is likely to decline. An alternative projection (B) is given to account for the U-shape distribution and urban fertility of 1.8 in 2000, increasing to and stabilizing at 2.2 in 2020, such that population estimates for 2000 are 1291 and 1524 for 2087 with a peak in 2048 of 1573. A faster fertility decline is also used to generate projection C. The author's projections A, B, and C, which are based on more recent data and a more realistic model, are than the "objective projection" and than the "warning projection" generated by China's Population Census Office based on 1982 census data.

Healthcare Costs Among Patients with Excessive Sleepiness Associated with Obstructive Sleep Apnea, Shift Work Disorder, or Narcolepsy

PubMed Central

Carlton, Rashad; Lunacsek, Orsolya; Regan, Timothy; Carroll, Cathryn A.

2014-01-01

Background Excessive daytime sleepiness affects nearly 20% of the general population and is associated with many medical conditions, including shift work disorder (SWD), obstructive sleep apnea (OSA), and narcolepsy. Excessive sleepiness imposes a significant clinical, quality-of-life, safety, and economic burden on society. Objective To compare healthcare costs for patients receiving initial therapy with armodafinil or with modafinil for the treatment of excessive sleepiness associated with OSA, SWD, or narcolepsy. Methods A retrospective cohort analysis of medical and pharmacy claims was conducted using the IMS LifeLink Health Plan Claims Database. Patients aged ≥18 years who had a pharmacy claim for armodafinil or for modafinil between June 1, 2009, and February 28, 2012, and had 6 months of continuous eligibility before the index prescription date, as well as International Classification of Diseases, Ninth Revision diagnosis for either OSA (327.23), SWD (327.36), or narcolepsy (347.0x) were included in the study. Patients were placed into 1 of 2 treatment cohorts based on their index prescription and followed for 1 month minimum and 34 months maximum. The annualized all-cause costs were calculated by multiplying the average per-month medical and pharmacy costs for each patient by 12 months. The daily average consumption (DACON) for armodafinil or for modafinil was calculated by dividing the total units dispensed of either drug by the prescription days supply. Results A total of 5693 patients receiving armodafinil and 9212 patients receiving modafinil were included in this study. A lower DACON was observed for armodafinil (1.04) compared with modafinil (1.47). The postindex mean medical costs were significantly lower for the armodafinil cohort compared with the modafinil cohort after adjusting for baseline differences ($11,363 vs $13,775, respectively; P = .005). The mean monthly drug-specific pharmacy costs were lower for the armodafinil cohort compared with the modafinil cohort ($166 vs $326, respectively; P <.001). In addition, lower total healthcare costs were observed for the armodafinil cohort compared with the modafinil cohort after correcting for baseline differences ($18,309 vs $23,530, respectively; P <.001). Conclusion As shown in this analysis, armodafinil may have real-world DACON advantages and may be associated with lower overall healthcare costs compared with modafinil. PMID:25558302

A New Approach to Age-Period-Cohort Analysis Using Partial Least Squares Regression: The Trend in Blood Pressure in the Glasgow Alumni Cohort

PubMed Central

Tu, Yu-Kang; Davey Smith, George; Gilthorpe, Mark S.

2011-01-01

Due to a problem of identification, how to estimate the distinct effects of age, time period and cohort has been a controversial issue in the analysis of trends in health outcomes in epidemiology. In this study, we propose a novel approach, partial least squares (PLS) analysis, to separate the effects of age, period, and cohort. Our example for illustration is taken from the Glasgow Alumni cohort. A total of 15,322 students (11,755 men and 3,567 women) received medical screening at the Glasgow University between 1948 and 1968. The aim is to investigate the secular trends in blood pressure over 1925 and 1950 while taking into account the year of examination and age at examination. We excluded students born before 1925 or aged over 25 years at examination and those with missing values in confounders from the analyses, resulting in 12,546 and 12,516 students for analysis of systolic and diastolic blood pressure, respectively. PLS analysis shows that both systolic and diastolic blood pressure increased with students' age, and students born later had on average lower blood pressure (SBP: −0.17 mmHg/per year [95% confidence intervals: −0.19 to −0.15] for men and −0.25 [−0.28 to −0.22] for women; DBP: −0.14 [−0.15 to −0.13] for men; −0.09 [−0.11 to −0.07] for women). PLS also shows a decreasing trend in blood pressure over the examination period. As identification is not a problem for PLS, it provides a flexible modelling strategy for age-period-cohort analysis. More emphasis is then required to clarify the substantive and conceptual issues surrounding the definitions and interpretations of age, period and cohort effects. PMID:21556329

Internet-based data inclusion in a population-based European collaborative follow-up study of inflammatory bowel disease patients: Description of methods used and analysis of factors influencing response rates

PubMed Central

Wolters, Frank L; van Zeijl, Gilbert; Sijbrandij, Jildou; Wessels, Frederik; O’Morain, Colm; Limonard, Charles; Russel, Maurice G; Stockbrügger, Reinhold W

2005-01-01

AIM: To describe an Internet-based data acquisition facility for a European 10-year clinical follow-up study project of a population-based cohort of inflammatory bowel disease (IBD) patients and to investigate the influence of demographic and disease related patient characteristics on response rates. METHODS: Thirteen years ago, the European Collaborative study group of IBD (EC-IBD) initiated a population-based prospective inception cohort of 2 201 uniformly diagnosed IBD patients within 20 well-described geographical areas in 11 European countries and Israel. For the 10-year follow-up of this cohort, an electronic patient questionnaire (ePQ) and electronic physician per patient follow-up form (ePpPFU) were designed as two separate data collecting instruments and made available through an Internet-based website. Independent demographic and clinical determinants of ePQ participation were analyzed using multivariate logistic regression. RESULTS: In 958 (316 CD and 642 UC) out of a total number of 1 505 (64%) available IBD patients, originating from 13 participating centers from nine different countries, both ePQ and ePpPFU were completed. Patients older than 40 years at ePQ completion (OR: 1.53 (95%CI: 1.14-2.05)) and those with active disease during the 3 mo previous to ePQ completion (OR: 3.32 (95%CI: 1.57-7.03)) were significantly more likely to respond. CONCLUSION: An Internet-based data acquisition tool appeared successful in sustaining a unique Western-European and Israelian multi-center 10-year clinical follow-up study project in patients afflicted with IBD. PMID:16437663

Internet-based data inclusion in a population-based European collaborative follow-up study of inflammatory bowel disease patients: description of methods used and analysis of factors influencing response rates.

PubMed

Wolters, Frank L; van Zeijl, Gilbert; Sijbrandij, Jildou; Wessels, Frederik; O'Morain, Colm; Limonard, Charles; Russel, Maurice G; Stockbrugger, Reinhold W

2005-12-07

To describe an Internet-based data acquisition facility for a European 10-year clinical follow-up study project of a population-based cohort of inflammatory bowel disease (IBD) patients and to investigate the influence of demographic and disease related patient characteristics on response rates. Thirteen years ago, the European Collaborative study group of IBD (EC-IBD) initiated a population-based prospective inception cohort of 2 201 uniformly diagnosed IBD patients within 20 well-described geographical areas in 11 European countries and Israel. For the 10-year follow-up of this cohort, an electronic patient questionnaire (ePQ) and electronic physician per patient follow-up form (ePpPFU) were designed as two separate data collecting instruments and made available through an Internet-based website. Independent demographic and clinical determinants of ePQ participation were analyzed using multivariate logistic regression. In 958 (316 CD and 642 UC) out of a total number of 1 505 (64%) available IBD patients, originating from 13 participating centers from nine different countries, both ePQ and ePpPFU were completed. Patients older than 40 years at ePQ completion (OR: 1.53 (95%CI: 1.14-2.05)) and those with active disease during the 3 mo previous to ePQ completion (OR: 3.32 (95%CI: 1.57-7.03)) were significantly more likely to respond. An Internet-based data acquisition tool appeared successful in sustaining a unique Western-European and Israelian multi-center 10-year clinical follow-up study project in patients afflicted with IBD.

Dietary patterns are associated with dietary recommendations but have limited relationship to BMI in the Communities Advancing the Studies of Tribal Nations Across the Lifespan (CoASTAL) cohort.

PubMed

Fialkowski, Marie K; McCrory, Megan A; Roberts, Sparkle M; Tracy, J Kathleen; Grattan, Lynn M; Boushey, Carol J

2012-10-01

Traditional food systems in indigenous groups have historically had health-promoting benefits. The objectives of the present study were to determine if a traditional dietary pattern of Pacific Northwest Tribal Nations (PNwT) could be derived using reduced rank regression and if the pattern would be associated with lower BMI and current Dietary Reference Intakes. The baseline data from the Communities Advancing the Studies of Tribal Nations Across the Lifespan (CoASTAL) cohort were used to derive dietary patterns for the total sample and those with plausibly reported energy intakes. Pacific Northwest Coast of Washington State, USA. Adult PNwT members of the CoASTAL cohort with laboratory-measured weight and height and up to 4 d of dietary records (n 418). A traditional dietary pattern did not evolve from the analysis. Moderate consumption of a sweet drinks dietary pattern was associated with lower BMI while higher consumption of a vegetarian-based dietary pattern was associated with higher BMI. The highest consumers of the vegetarian-based dietary pattern were almost six times more likely to meet the recommendations for dietary fibre. Distinct dietary patterns were found. Further exploration is needed to confirm whether the lack of finding a traditional pattern is due to methodology or the loss of a traditional dietary pattern among this population. Longitudinal assessment of the CoASTAL cohort's dietary patterns needs to continue.

Genome-wide association study identifies SNPs in the MHC class II loci that are associated with self-reported history of whooping cough

PubMed Central

McMahon, George; Ring, Susan M.; Davey-Smith, George; Timpson, Nicholas J.

2015-01-01

Whooping cough is currently seeing resurgence in countries despite high vaccine coverage. There is considerable variation in subject-specific response to infection and vaccine efficacy, but little is known about the role of human genetics. We carried out a case–control genome-wide association study of adult or parent-reported history of whooping cough in two cohorts from the UK: the ALSPAC cohort and the 1958 British Birth Cohort (815/758 cases and 6341/4308 controls, respectively). We also imputed HLA alleles using dense SNP data in the MHC region and carried out gene-based and gene-set tests of association and estimated the amount of additive genetic variation explained by common SNPs. We observed a novel association at SNPs in the MHC class II region in both cohorts [lead SNP rs9271768 after meta-analysis, odds ratio [95% confidence intervals (CIs)] 1.47 (1.35, 1.6), P-value 1.21E − 18]. Multiple strong associations were also observed at alleles at the HLA class II loci. The majority of these associations were explained by the lead SNP rs9271768. Gene-based and gene-set tests and estimates of explainable common genetic variation could not establish the presence of additional associations in our sample. Genetic variation at the MHC class II region plays a role in susceptibility to whooping cough. These findings provide additional perspective on mechanisms of whooping cough infection and vaccine efficacy. PMID:26231221

Anxiety and depressive disorders among patients with esophageal cancer in Taiwan: a nationwide population-based study.

PubMed

Hu, Li-Yu; Ku, Fan-Chen; Wang, Yen-Po; Shen, Cheng-Che; Hu, Yu-Wen; Yeh, Chiu-Mei; Chen, Pan-Ming; Chiang, Huey-Ling; Lu, Ti; Chen, Tzeng-Ji; Teng, Chung-Jen; Liu, Chia-Jen

2015-03-01

The comorbidity of depression with anxiety disorders is associated with poorer treatment outcomes, worse quality of life, poorer adherence to treatment, and greater suicide risk in cancer patients. To assess the risk of comorbid anxiety and depressive disorders after the diagnosis of esophageal cancer compared with a matched cohort by using the Taiwan National Health Insurance Research Database (NHIRD). We conducted a retrospective study of 28,454 patients (14,227 patients with esophageal cancer and 14,227 matched patients) who were selected from the NHIRD. Patients were observed for a maximum of 12 years to determine the incidence of new-onset anxiety and depressive disorders for which antidepressants had been prescribed. A Cox regression analysis was performed to identify the risk factors associated with anxiety and depressive disorders in esophageal cancer patients. The cumulative incidence of anxiety and depressive disorders in the esophageal cancer patients was significantly higher than that in the matched cohort (P < .001). The adjusted hazard ratio (HR) was 2.24 (95 % confidence interval, CI = 1.95-2.56, P < .001) in the esophageal cancer cohort compared with the matched cohort. Independent risk factors for developing anxiety and depressive disorders among the patients with esophageal cancer included cirrhosis, cerebrovascular disease, and surgical treatment. Esophageal cancer may be a prominent risk factor for anxiety and depressive disorders. Based on our data, we suggest that attention should be focused on esophageal cancer patients with comorbid cirrhosis and cerebrovascular disease and those who have received surgical interventions.

Comparison of bias analysis strategies applied to a large data set.

PubMed

Lash, Timothy L; Abrams, Barbara; Bodnar, Lisa M

2014-07-01

Epidemiologic data sets continue to grow larger. Probabilistic-bias analyses, which simulate hundreds of thousands of replications of the original data set, may challenge desktop computational resources. We implemented a probabilistic-bias analysis to evaluate the direction, magnitude, and uncertainty of the bias arising from misclassification of prepregnancy body mass index when studying its association with early preterm birth in a cohort of 773,625 singleton births. We compared 3 bias analysis strategies: (1) using the full cohort, (2) using a case-cohort design, and (3) weighting records by their frequency in the full cohort. Underweight and overweight mothers were more likely to deliver early preterm. A validation substudy demonstrated misclassification of prepregnancy body mass index derived from birth certificates. Probabilistic-bias analyses suggested that the association between underweight and early preterm birth was overestimated by the conventional approach, whereas the associations between overweight categories and early preterm birth were underestimated. The 3 bias analyses yielded equivalent results and challenged our typical desktop computing environment. Analyses applied to the full cohort, case cohort, and weighted full cohort required 7.75 days and 4 terabytes, 15.8 hours and 287 gigabytes, and 8.5 hours and 202 gigabytes, respectively. Large epidemiologic data sets often include variables that are imperfectly measured, often because data were collected for other purposes. Probabilistic-bias analysis allows quantification of errors but may be difficult in a desktop computing environment. Solutions that allow these analyses in this environment can be achieved without new hardware and within reasonable computational time frames.

Reduction in incidence of Johne's disease associated with implementation of a disease control program in Minnesota demonstration herds.

PubMed

Espejo, L A; Godden, S; Hartmann, W L; Wells, S J

2012-07-01

This prospective longitudinal observational study was conducted to evaluate the effect of a standardized control program on the incidence of Johne's disease in 8 dairy herds in Minnesota. Depending on recruitment year, herds were followed for between 5 and 10 yr. Program compliance was evaluated using a cohort risk assessment score by birth cohort. Fecal samples from cows in study herds were tested annually using bacterial culture to detect Mycobacterium avium ssp. paratuberculosis (MAP), and serum samples from study cows were tested using an ELISA to detect antibodies to MAP. Clinical Johne's disease was also recorded. Cohort risk assessment score decreased along birth cohorts. Depending on the follow-up period in each herd, 5 to 8 birth cohorts were followed to describe changes in time to MAP bacterial culture positivity, serum ELISA positivity, MAP heavy shedding status, and clinical Johne's disease. The analysis of time to bacterial culture positivity, serum ELISA positivity, heavy fecal shedding status, and clinical Johne's disease using a time-dependent Cox regression indicated a reduction of the instantaneous hazard ratio by birth cohorts and by cohort risk score; however, the strength of association between the cohort risk score and each of the 4 disease outcomes decreased over time. The age at which the cows first tested positive for bacterial culture, serum ELISA, and heavy fecal shedding, and the age of the cows at onset of clinical Johne's disease signs remained constant for all birth cohorts. Based on herd risk scores, overall herds complied with the recommended management practices in the program. Results were consistent with a within-herd reduction of Johne's disease transmission, and that reduction was associated with herd-level management practices implemented as part of the control program. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model: A Web-based program designed to evaluate the cost-effectiveness of disease management programs in heart failure.

PubMed

Reed, Shelby D; Neilson, Matthew P; Gardner, Matthew; Li, Yanhong; Briggs, Andrew H; Polsky, Daniel E; Graham, Felicia L; Bowers, Margaret T; Paul, Sara C; Granger, Bradi B; Schulman, Kevin A; Whellan, David J; Riegel, Barbara; Levy, Wayne C

2015-11-01

Heart failure disease management programs can influence medical resource use and quality-adjusted survival. Because projecting long-term costs and survival is challenging, a consistent and valid approach to extrapolating short-term outcomes would be valuable. We developed the Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model, a Web-based simulation tool designed to integrate data on demographic, clinical, and laboratory characteristics; use of evidence-based medications; and costs to generate predicted outcomes. Survival projections are based on a modified Seattle Heart Failure Model. Projections of resource use and quality of life are modeled using relationships with time-varying Seattle Heart Failure Model scores. The model can be used to evaluate parallel-group and single-cohort study designs and hypothetical programs. Simulations consist of 10,000 pairs of virtual cohorts used to generate estimates of resource use, costs, survival, and incremental cost-effectiveness ratios from user inputs. The model demonstrated acceptable internal and external validity in replicating resource use, costs, and survival estimates from 3 clinical trials. Simulations to evaluate the cost-effectiveness of heart failure disease management programs across 3 scenarios demonstrate how the model can be used to design a program in which short-term improvements in functioning and use of evidence-based treatments are sufficient to demonstrate good long-term value to the health care system. The Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model provides researchers and providers with a tool for conducting long-term cost-effectiveness analyses of disease management programs in heart failure. Copyright © 2015 Elsevier Inc. All rights reserved.

Mediterranean diet adherence during pregnancy and risk of wheeze and eczema in the first year of life: INMA (Spain) and RHEA (Greece) mother-child cohort studies.

PubMed

Chatzi, Leda; Garcia, Raquel; Roumeliotaki, Theano; Basterrechea, Mikel; Begiristain, Haizea; Iñiguez, Carmen; Vioque, Jesus; Kogevinas, Manolis; Sunyer, Jordi

2013-12-14

Maternal diet during pregnancy might influence the development of childhood allergic disorders. The aim of the present study was to evaluate the impact of Mediterranean diet (MD) adherence during pregnancy on wheeze and eczema in the first year of life in two population-based mother-child cohorts in Spain and Greece. We studied 1771 mother-newborn pairs from the Spanish multi-centre 'INMA' (INfancia y Medio Ambiente) study (Gipuzkoa, Sabadell and Valencia) and 745 pairs from the 'RHEA' study in Crete, Greece. The symptoms of wheeze and eczema were based on the criteria of the International Study of Asthma and Allergies in Childhood. Maternal diet during pregnancy was assessed by FFQ and MD adherence was evaluated through an a priori score. Multivariate log-binomial regression models were used to adjust for several confounders in each cohort and summary estimates were obtained by a meta-analysis. MD adherence was not associated with the risk of wheeze and eczema in any cohort, and similar results were identified in the meta-analysis approach. High meat intake (relative risk (RR) 1·22, 95 % CI 1·00, 1·49) and 'processed' meat intake (RR 1·18, 95 % CI 1·02, 1·37) during pregnancy were associated with an increased risk of wheeze in the first year of life, while a high intake of dairy products was significantly associated with a decreased risk of infantile wheeze (RR 0·83, 95 % CI 0·72, 0·96). The results of the present study show that high meat intake during pregnancy may increase the risk of wheeze in the first year of life, while a high intake of dairy products may decrease it.

Statin use after esophageal cancer diagnosis and survival: A population based cohort study.

PubMed

Cardwell, Chris R; Spence, Andrew D; Hughes, Carmel M; Murray, Liam J

2017-06-01

A recent epidemiological study of esophageal cancer patients concluded statin use post-diagnosis was associated with large (38%) and significant reductions in cancer-specific mortality. We investigated statin use and cancer-specific mortality in a large population-based cohort of esophageal cancer patients. Newly diagnosed [2009-2012] esophageal cancer patients were identified from the Scottish Cancer Registry and linked with the Prescribing Information System and Scotland Death Records (to January 2015). Time-dependent Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% confidence intervals (CIs) by post-diagnostic statin use (using a 6 month lag to reduce reverse causation) and to adjust these HRs for potential confounders. 1921 esophageal cancer patients were included in the main analysis, of whom 651 (34%) used statins after diagnosis. There was little evidence of a reduction in esophageal cancer-specific mortality in statin users compared with non-users after diagnosis (adjusted HR=0.93, 95% CI, 0.81, 1.07) and no dose response associations were seen. However, statin users compared with non-users in the year before diagnosis had a weak reduction in esophageal cancer-specific mortality (adjusted HR=0.88, 95% CI, 0.79, 0.99). In this large population-based esophageal cancer cohort, there was little evidence of a reduction in esophageal cancer-specific mortality with statin use after diagnosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association of rheumatoid arthritis with allergic diseases: A nationwide population-based cohort study.

PubMed

Lai, Ning-Sheng; Tsai, Tzung-Yi; Koo, Malcolm; Lu, Ming-Chi

2015-01-01

Low-grade inflammation conditions, e.g., type 2 diabetes, have been shown to be associated with an increased risk of rheumatoid arthritis (RA). However, the association between other chronic inflammatory conditions, e.g., asthma, allergic rhinitis, and atopic dermatitis, is still unclear. To investigate the risk of RA in patients with allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis, by using a nationwide health claims database. The Taiwan National Health Insurance Research Database was used to assemble a cohort of 170,570 patients ages 20 years old and older diagnosed with allergic diseases, including asthma, allergic rhinitis, or atopic dermatitis. A comparison cohort of 170,238 patients was constructed from the same data base, with frequency matching for sex, 10-year age group, and year of insurance enrollment. Cox proportional hazards regression analyses were conducted to assess the association between the allergic diseases and incident RA. Asthma (adjusted hazard ratio [AHR] 1.67, [95% confidence interval {CI}], 1.32-2.62) and allergic rhinitis (AHR 1.62 [95% CI, 1.33-1.98]) were significantly associated with the incident RA. These associations remained significant even after excluding patients who had concurrent diagnoses of asthma and allergic rhinitis. Patients with more than one allergic disease had an increased risk of developing RA (AHR 1.98 [95% CI, 1.50-2.62]). Subgroup analysis further indicated that middle-aged and elderly female patients with more than one allergic disease exhibited a high risk of developing RA. Significant associations between common allergic diseases and incident RA was found in this population-based cohort study. Our findings provided support to the hypothesis that allergic diseases and RA might share a similar underlying etiologic pathway related to chronic inflammatory responses.

Clinical, biomarker, and genetic predictors of specific types of atrial fibrillation in a community-based cohort: data of the PREVEND study.

PubMed

Hobbelt, Anne H; Siland, Joylene E; Geelhoed, Bastiaan; Van Der Harst, Pim; Hillege, Hans L; Van Gelder, Isabelle C; Rienstra, Michiel

2017-02-01

Atrial fibrillation (AF) may present variously in time, and AF may progress from self-terminating to non-self-terminating AF, and is associated with impaired prognosis. However, predictors of AF types are largely unexplored. We investigate the clinical, biomarker, and genetic predictors of development of specific types of AF in a community-based cohort. We included 8042 individuals (319 with incident AF) of the PREVEND study. Types of AF were compared, and multivariate multinomial regression analysis determined associations with specific types of AF. Mean age was 48.5 ± 12.4 years and 50% were men. The types of incident AF were ascertained based on electrocardiograms; 103(32%) were classified as AF without 2-year recurrence, 158(50%) as self-terminating AF, and 58(18%) as non-self-terminating AF. With multivariate multinomial logistic regression analysis, advancing age (P< 0.001 for all three types) was associated with all AF types, male sex was associated with AF without 2-year recurrence and self-terminating AF (P= 0.031 and P= 0.008, respectively). Increasing body mass index and MR-proANP were associated with both self-terminating (P= 0.009 and P< 0.001) and non-self-terminating AF (P= 0.003 and P< 0.001). The only predictor associated with solely self-terminating AF is prescribed anti-hypertensive treatment (P= 0.019). The following predictors were associated with non-self-terminating AF; lower heart rate (P= 0.018), lipid-lowering treatment prescribed (P= 0.009), and eGFR <60 mL/min/1.73 m2 (P= 0.006). Three known AF-genetic variants (rs6666258, rs6817105, and rs10821415) were associated with self-terminating AF. We found clinical, biomarker and genetic predictors of specific types of incident AF in a community-based cohort. The genetic background seems to play a more important role than modifiable risk factors in self-terminating AF.

Preliminary Rural Analysis of the Early Childhood Longitudinal Study--Kindergarten Cohort. Rural Early Childhood Brief Number 2

ERIC Educational Resources Information Center

National Center for Rural Early Childhood Learning Initiatives - Mississippi State University Early Childhood Institute, 2005

2005-01-01

This brief introduces the first results from a rural analysis of selected national datasets. Provided are key findings concerning kindergarten readiness of rural children from an analysis of the Kindergarten Cohort of the Early Childhood Longitudinal Study (ECLS). Future briefs will summarize the findings concerning the health of the Kindergarten…

Distinct contributions of adverse childhood experiences and resilience resources: a cohort analysis of adult physical and mental health.

PubMed

Logan-Greene, Patricia; Green, Sara; Nurius, Paula S; Longhi, Dario

2014-01-01

Although evidence is rapidly amassing as to the damaging potential of early life adversities on physical and mental health, as yet few investigations provide comparative snapshots of these patterns across adulthood. This population-based study addresses this gap, examining the relationship of adverse childhood experiences (ACEs) to physical and mental health within a representative sample (n = 19,333) of adults, comparing the prevalence and explanatory strength of ACEs among four birth cohorts spanning ages 18-79. This assessment accounts for demographic and socioeconomic factors, as well as both direct and moderating effects of resilience resources (social/emotional support, life satisfaction, and sleep quality). Findings demonstrate (1) increasing trends of reported ACEs across younger cohorts, including time period shifts such as more prevalent family incarceration, substance abuse, and divorce, (2) significant bivariate as well as independent associations of ACEs with poor health within every cohort, controlling for multiple covariates (increasing trends in older age for physical health), and (3) robust patterns wherein resilience resources moderated ACEs, indicating buffering pathways that sustained into old age. Theoretical and practice implications for health professionals are discussed.

Application of Large-Scale Aptamer-Based Proteomic Profiling to Planned Myocardial Infarctions.

PubMed

Jacob, Jaison; Ngo, Debby; Finkel, Nancy; Pitts, Rebecca; Gleim, Scott; Benson, Mark D; Keyes, Michelle J; Farrell, Laurie A; Morgan, Thomas; Jennings, Lori L; Gerszten, Robert E

2018-03-20

Emerging proteomic technologies using novel affinity-based reagents allow for efficient multiplexing with high-sample throughput. To identify early biomarkers of myocardial injury, we recently applied an aptamer-based proteomic profiling platform that measures 1129 proteins to samples from patients undergoing septal alcohol ablation for hypertrophic cardiomyopathy, a human model of planned myocardial injury. Here, we examined the scalability of this approach using a markedly expanded platform to study a far broader range of human proteins in the context of myocardial injury. We applied a highly multiplexed, expanded proteomic technique that uses single-stranded DNA aptamers to assay 4783 human proteins (4137 distinct human gene targets) to derivation and validation cohorts of planned myocardial injury, individuals with spontaneous myocardial infarction, and at-risk controls. We found 376 target proteins that significantly changed in the blood after planned myocardial injury in a derivation cohort (n=20; P <1.05E-05, 1-way repeated measures analysis of variance, Bonferroni threshold). Two hundred forty-seven of these proteins were validated in an independent planned myocardial injury cohort (n=15; P <1.33E-04, 1-way repeated measures analysis of variance); >90% were directionally consistent and reached nominal significance in the validation cohort. Among the validated proteins that were increased within 1 hour after planned myocardial injury, 29 were also elevated in patients with spontaneous myocardial infarction (n=63; P <6.17E-04). Many of the novel markers identified in our study are intracellular proteins not previously identified in the peripheral circulation or have functional roles relevant to myocardial injury. For example, the cardiac LIM protein, cysteine- and glycine-rich protein 3, is thought to mediate cardiac mechanotransduction and stress responses, whereas the mitochondrial ATP synthase F 0 subunit component is a vasoactive peptide on its release from cells. Last, we performed aptamer-affinity enrichment coupled with mass spectrometry to technically verify aptamer specificity for a subset of the new biomarkers. Our results demonstrate the feasibility of large-scale aptamer multiplexing at a level that has not previously been reported and with sample throughput that greatly exceeds other existing proteomic methods. The expanded aptamer-based proteomic platform provides a unique opportunity for biomarker and pathway discovery after myocardial injury. © 2017 American Heart Association, Inc.

Association of Warfarin Use With Lower Overall Cancer Incidence Among Patients Older Than 50 Years.

PubMed

Haaland, Gry S; Falk, Ragnhild S; Straume, Oddbjørn; Lorens, James B

2017-12-01

In cancer models, warfarin inhibits AXL receptor tyrosine kinase-dependent tumorigenesis and enhances antitumor immune responses at doses not reaching anticoagulation levels. This study investigates the association between warfarin use and cancer incidence in a large, unselected population-based cohort. To examine the association between warfarin use and cancer incidence. This population-based cohort study with subgroup analysis used the Norwegian National Registry coupled with the Norwegian Prescription Database and the Cancer Registry of Norway. The cohort comprised all persons (N = 1 256 725) born between January 1, 1924, and December 31, 1954, who were residing in Norway from January 1, 2006, through December 31, 2012. The cohort was divided into 2 groups-warfarin users and nonusers; persons taking warfarin for atrial fibrillation or atrial flutter were the subgroup. Data were collected from January 1, 2004, to December 31, 2012. Data analysis was conducted from October 15, 2016, to January 31, 2017. Warfarin use was defined as taking at least 6 months of a prescription and at least 2 years from first prescription to any cancer diagnosis. If warfarin treatment started after January 1, 2006, each person contributed person-time in the nonuser group until the warfarin user criteria were fulfilled. Cancer diagnosis of any type during the 7-year observation period (January 1, 2006, through December 31, 2012). Of the 1 256 725 persons in the cohort, 607 350 (48.3%) were male, 649 375 (51.7%) were female, 132 687 (10.6%) had cancer, 92 942 (7.4%) were classified as warfarin users, and 1 163 783 (92.6%) were classified as nonusers. Warfarin users were older, with a mean (SD) age of 70.2 (8.2) years, and were predominantly men (57 370 [61.7%]) as compared with nonusers, who had a mean (SD) age of 63.9 (8.6) years and were mostly women (613 803 [52.7%]). Among warfarin users and compared with nonusers, there was a significantly lower age- and sex-adjusted incidence rate ratio (IRR) in all cancer sites (IRR, 0.84; 95% CI, 0.82-0.86) and in prevalent organ-specific sites (lung, 0.80 [95% CI, 0.75-0.86]; prostate, 0.69 [95% CI, 0.65-0.72]; and breast, 0.90 [95% CI, 0.82-1.00]). There was no observed significant effect in colon cancer (IRR, 0.99; 95% CI, 0.93-1.06). In a subgroup analysis of patients with atrial fibrillation or atrial flutter, the IRR was lower in all cancer sites (IRR, 0.62; 95% CI, 0.59-0.65) and in prevalent sites (lung, 0.39 [95% CI, 0.33-0.46]; prostate, 0.60 [95% CI, 0.55-0.66]; breast, 0.72 [95% CI, 0.59-0.87]; and colon, 0.71 [95% CI, 0.63-0.81]). Warfarin use may have broad anticancer potential in a large, population-based cohort of persons older than 50 years. This finding could have important implications for the selection of medications for patients needing anticoagulation.

Screening for Wilms tumor and hepatoblastoma in children with Beckwith-Wiedemann syndromes: a cost-effective model.

PubMed

McNeil, D E; Brown, M; Ching, A; DeBaun, M R

2001-10-01

We undertook a cost-benefit analysis of screening for Wilms tumor and hepatoblastoma in children with Beckwith-Wiedemann syndrome (BWS), a known cancer predisposition syndrome. The purpose of this analysis was twofold: first, to assess whether screening in children with BWS has the potential to be cost-effective; second, if screening appears to be cost-effective, to determine which parameters would be most important to assess if a screening trial were initiated. We used data from the BWS registry at the National Cancer Institute, the National Wilms Tumor Study (NWTS), and large published series to model events for two hypothetical cohorts of 1,000 infants born with BWS. One hypothetical cohort was screened for cancer until a predetermined age, representing the base case. The other cohort was unscreened. For our base case, we assumed: (a) sonography examinations three times yearly (triannually) from birth until 7 years of age; (b) screening would result in one stage shift downward at diagnosis for Wilms tumor and hepatoblastoma; (c) 100% sensitivity and 95% specificity for detecting clinical stage I Wilms tumor and hepatoblastoma; (d) a 3% discount rate; (e) a false positive result cost of $402. We estimated mortality rates based on published Wilms tumor and hepatoblastoma stage specific survival. Using the base case, screening a child with BWS from birth until 4 years of age results in a cost per life year saved of $9,642 while continuing until 7 years of age results in a cost per life-year saved of $14,740. When variables such as cost of screening examination, discount rate, and effectiveness of screening were varied based on high and low estimates, the incremental cost per life-year saved for screening up until age four remained comparable to acceptable population based cancer screening ranges (< $50,000 per life year saved). Under our model's assumptions, abdominal sonography examinations in children with BWS represent a reasonable strategy for a cancer screening program. A cancer screening trial is warranted to determine if, when, and how often children with BWS should be screened and to determine cost-effectiveness in clinical practice. Published 2001 Wiley-Liss, Inc.

Increasing Use of Nonmedical Analgesics Among Younger Cohorts in the United States: A Birth Cohort Effect

PubMed Central

Miech, Richard; Bohnert, Amy; Heard, Kennon; Boardman, Jason

2017-01-01

Purpose Nonmedical use of prescription pain drugs (hereafter ‘analgesics’) has increased substantially in recent years. It is not known whether today’s youth are disproportionately driving this increase or, instead, the trend is a general one that has affected cohorts of all ages similarly. To address this question we present the first age-period-cohort analysis of nonmedical use of analgesics. Methods Data come from the National Survey on Drug Use and Health, a series of annual, nationally-representative, cross-sectional surveys of the U.S. civilian, non-institutionalized population. The analysis focuses on the years 1985 to 2009 and uses the recently developed ‘intrinsic estimator’ algorithm to disentangle age-period-cohort effects. Results Substantial increases in the prevalence of nonmedical analgesics use have occurred across all cohorts and ages in recent years, but this increase is significantly amplified among today’s adolescents. The odds of past-year, nonmedical analgesics use for today’s youngest cohort (born 1980–1994) are higher than would be expected on the basis of their age and broad, historical period influences that have increased use across people of all ages and cohorts. The independent influence of cohort on past-year, nonmedical analgesics use is about 40% higher for today’s youth cohort than any of the cohorts that came before them. This finding is present among men, women, non-Hispanic whites, non-Hispanic blacks, and Hispanics. Conclusions Although nonmedical use of analgesics is evident among all ages, cohorts, and periods, today’s younger cohorts warrant special attention for substance abuse policies and interventions targeted at reversing the increase in nonmedical analgesics use. PMID:23260832

Birth order and mortality: a population-based cohort study.

PubMed

Barclay, Kieron; Kolk, Martin

2015-04-01

This study uses Swedish population register data to investigate the relationship between birth order and mortality at ages 30 to 69 for Swedish cohorts born between 1938 and 1960, using a within-family comparison. The main analyses are conducted with discrete-time survival analysis using a within-family comparison, and the estimates are adjusted for age, mother's age at the time of birth, and cohort. Focusing on sibships ranging in size from two to six, we find that mortality risk in adulthood increases with later birth order. The results show that the relative effect of birth order is greater among women than among men. This pattern is consistent for all the major causes of death but is particularly pronounced for mortality attributable to cancers of the respiratory system and to external causes. Further analyses in which we adjust for adult socioeconomic status and adult educational attainment suggest that social pathways only mediate the relationship between birth order and mortality risk in adulthood to a limited degree.

Impact of a Pharmacy-Cardiology Collaborative Practice on Dofetilide Safety Monitoring.

PubMed

Quffa, Lieth H; Panna, Mark; Kaufmann, Michael R; McKillop, Matthew; Dietrich, Nicole Maltese; Franck, Andrew J

2017-01-01

Limited studies have been published examining dofetilide's postmarketing use and its recommended monitoring. To evaluate the impact of a collaborative pharmacy-cardiology antiarrhythmic drug (AAD) monitoring program on dofetilide monitoring. This retrospective cohort study was performed to assess if a novel monitoring program improved compliance with dofetilide-specific monitoring parameters based on the Food and Drug Administration's Risk Evaluation and Mitigation Strategy. A total of 30 patients were included in the analysis. The monitoring parameters evaluated included electrocardiogram, serum potassium, serum magnesium, and kidney function. The primary outcome evaluated was the composite of these dofetilide monitoring parameters obtained in each cohort. In the standard cohort, 245 of 352 (69.6%) monitoring parameters were completed versus 134 of 136 (98.5%) in the intervention group ( P < 0.05). A collaborative pharmacy-cardiology AAD monitoring program was associated with a significant improvement in dofetilide monitoring. This improvement could potentially translate into enhanced patient safety outcomes, such as prevention of adverse drug reactions and decreased hospitalizations.

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

PubMed

Borgan, Ørnulf; Keogh, Ruth

2015-10-01

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

Student Loans and the Likelihood of Graduation: Evidence from Finnish Cohort Data

ERIC Educational Resources Information Center

Asplund, Rita; Abdelkarim, Oussama Ben; Skalli, Ali

2009-01-01

Most countries have experienced soaring enrolment rates into tertiary education. While this is beneficial both to involved students and to knowledge-based societies, it also makes the funding issue even more crucial than it is usually seen to be. This paper presents first results from an analysis of the effectiveness of student loans as a funding…

Grades in Selected First-Year Courses by ELT Status.

ERIC Educational Resources Information Center

Windham, Patricia

This report presents tables of grades in selected first-year courses by entry-level placement test (ELT) status in Florida community colleges. The cohort used in this analysis consisted of the fall 1993 students with ELT scores as reported in the 1993-94 Student Data Base (SDB). Students who took an ELT were divided into those who passed and those…

Grades and Graduation: A Longitudinal Risk Perspective to Identify Student Dropouts

ERIC Educational Resources Information Center

Bowers, Alex J.

2010-01-01

Studies of student risk of school dropout have shown that present predictors of at-risk status do not accurately identify a large percentage of students who eventually drop out. Through the analysis of the entire Grade 1-12 longitudinal cohort-based grading histories of the class of 2006 for two school districts in the United States, the author…

Competence in Mathematics and Academic Achievement: An Analysis of Enrollees in the Bachelor of Science in Actuarial Science Program

ERIC Educational Resources Information Center

Wamala, Robert; Maswere, Dyson W.; Mwanga, Yeko

2013-01-01

This study investigates the role of prior grounding attained in mathematics in predicting the academic achievement of enrollees in Bachelor of Science in Actuarial Science (BSAS). The investigation is based on administrative records of 240 BSAS enrollees at Makerere University, School of Statistics and Planning in the 2007-2009 cohorts. Students'…

Paternal exposure to medical-related radiation associated with low birthweight infants

PubMed Central

Chen, Shi; Yang, Yingying; QV, Yimin; Zou, Yun; ZHU, Huijuan; Gong, Fengying; Zou, Yongwei; Yang, Hongbo; WANG, Linjie; Lian, Bill Q.; Liu, Cynthia; Jiang, Yu; Yan, Chengsheng; LI, Jianqiang; Wang, Qing; Pan, Hui

2018-01-01

Abstract Low birthweight (LBW) is closely associated with fetal and perinatal mortality and morbidity. We identified the risk factors of LBW and geographical differences in LBW incidence in 30 Chinese provinces in the present study. This study was a population-based, retrospective cohort study performed in 30 Chinese provinces. We used data from the free National Pre-pregnancy Checkups Project, which is a countrywide population-based retrospective cohort study. To identify regional differences in LBW incidence, we used the Qinling-Huaihe climate line to divide China into northern and southern sections and the Heihe-Tengchong economic line to divide it into eastern and western sections. Multivariate unconditional logistic regression analysis with SAS 9.4 was used for data analysis. P < .05 was considered statistically significant. LBW incidence was 4.54% in rural China. Southern China had a significantly higher incidence (4.65%) than northern China (4.28%). Our main risk factor for LBW is paternal exposure to radiation (odds ratio = 1.537), which has never been studied before. This study identifies multiple risk factors of couples giving birth to LBW babies including paternal risk factors. PMID:29480847

Understanding heterogeneity in grey matter research of adults with childhood maltreatment-A meta-analysis and review.

PubMed

Paquola, Casey; Bennett, Maxwell R; Lagopoulos, Jim

2016-10-01

Childhood trauma has been associated with long term effects on prefrontal-limbic grey matter. A literature search was conducted to identify structural magnetic resonance imaging studies of adults with a history of childhood trauma. We performed three meta-analyses. Hedges' g effect sizes were calculated for each study providing hippocampal or amygdala volumes of trauma and non-trauma groups. Seed based differential mapping was utilised to synthesise whole brain voxel based morphometry (VBM) studies. A total of 38 articles (17 hippocampus, 13 amygdala, 19 whole brain VBM) were included in the meta-analyses. Trauma cohorts exhibited smaller hippocampus and amygdala volumes bilaterally. The most robust findings of the whole brain VBM meta-analysis were reduced grey matter in the right dorsolateral prefrontal cortex and right hippocampus amongst adults with a history of childhood trauma. Subgroup analyses and meta-regressions showed results were moderated by age, gender, the cohort's psychiatric health and the study's definition of childhood trauma. We provide evidence of abnormal grey matter in prefrontal-limbic brain regions of adults with a history of childhood maltreatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Maternal smoking during pregnancy and the risk of pediatric cardiovascular diseases of the offspring: A population-based cohort study with up to 18-years of follow up.

PubMed

Leybovitz-Haleluya, Noa; Wainstock, Tamar; Landau, Daniella; Sheiner, Eyal

2018-06-01

Cigarette smoke is a well-known reproductive toxicant. We aimed to study the long-term effect of cigarette smoking during pregnancy on the risk for childhood cardiovascular morbidity of the offspring. A population-based cohort analysis was performed comparing total and subtypes of cardiovascular related pediatric hospitalizations among offspring of smoking mothers versus offspring of non-smoking mothers. The analysis included all singletons born between the years 1999-2014.A Kaplan-Meier survival curve was used to compare the cumulative cardiovascular morbidity, and a Cox proportional hazards model was constructed to adjust for confounders. The study population included 242,342 newborns which met inclusion criteria; among them 2861 were born to smoking mothers. Offspring of smoking mothers had higher rates of cardiovascular-related hospitalizations (1.3% vs. 0.6%, OR 2.1, 95% CI 1.5-2.9; p < 0.001; Kaplan-Meier log-rank test p < 0.001). Smoking exposure during pregnancy is associated with an increased risk for long-term pediatric cardiovascular morbidity of the offspring. Copyright © 2018 Elsevier Inc. All rights reserved.

Cancer Incidence in Physicians

PubMed Central

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

2015-01-01

Abstract Cancer has been the leading cause of death in Taiwan since 1982. Physicians have many health-related risk factors which may contribute to cancer, such as rotating night shift, radiation, poor lifestyle, and higher exposure risk to infection and potential carcinogenic drugs. However, the cancer risk in physicians is not clear. In Taiwan's National Health Insurance Research Database, we identified 14,889 physicians as the study cohort and randomly selected 29,778 nonmedical staff patients as the comparison cohort for this national population-based cohort study. Cox proportional-hazard regression was used to compare the cancer risk between physicians and comparisons. Physician subgroups were also analyzed. Physicians had a lower all-cancer risk than did the comparisons (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.76–0.97). In the sex-based analysis, male physicians had a lower all-cancer risk than did male comparisons (HR 0.82, 95% CI 0.73–0.94); and female physicians did not (HR 1.29, 95% CI 0.88–1.91). In the cancer-type analysis, male physicians had a higher risk of prostate cancer (HR 1.72, 95% CI 1.12–2.65) and female physicians had twice the risk of breast cancer (HR 2.00, 95% CI 1.11–3.62) than did comparisons. Cancer risk was not significantly associated with physician specialties. Physicians in Taiwan had a lower all-cancer risk but higher risks for prostate and breast cancer than did the general population. These new epidemiological findings require additional study to clarify possible mechanisms. PMID:26632715

Prognostic value of platelet-to-lymphocyte ratio in pancreatic cancer: a comprehensive meta-analysis of 17 cohort studies.

PubMed

Zhou, Yongping; Cheng, Sijin; Fathy, Abdel Hamid; Qian, Haixin; Zhao, Yongzhao

2018-01-01

Several studies were conducted to explore the prognostic value of platelet-to-lymphocyte ratio (PLR) in pancreatic cancer and have reported contradictory results. This study aims to summarize the prognostic role of PLR in pancreatic cancer. Embase, PubMed and Cochrane Library were completely searched. The cohort studies focusing on the prognostic role of PLR in pancreatic cancer were eligible. The overall survival (OS) and progression-free survival (PFS) were analyzed. Fifteen papers containing 17 cohort studies with pancreatic cancer were identified. The results showed patients that with low PLR might have longer OS when compared to the patients with high PLR (hazard ratio=1.28, 95% CI=1.17-1.40, P <0.00001; I 2 =42%). Similar results were observed in the subgroup analyses of OS, which was based on the analysis model, ethnicity, sample size and cut-off value. Further analyses based on the adjusted potential confounders were conducted, including CA199, neutrophil-to-lymphocyte ratio, modified Glasgow Prognostic Score, albumin, C-reactive protein, Eastern Cooperative Oncology Group, stage, tumor size, nodal involvement, tumor differentiation, margin status, age and gender, which confirmed that low PLR was a protective factor in pancreatic cancer. In addition, low PLR was significantly associated with longer PFS when compared to high PLR in pancreatic cancer (hazard ratio=1.27, 95% CI=1.03-1.57, P =0.03; I 2 =33%). In conclusion, it was found that high PLR is an unfavorable predictor of OS and PFS in patients with pancreatic cancer, and PLR is a promising prognostic biomarker for pancreatic cancer.

Brain structure differences between Chinese and Caucasian cohorts: A comprehensive morphometry study.

PubMed

Tang, Yuchun; Zhao, Lu; Lou, Yunxia; Shi, Yonggang; Fang, Rui; Lin, Xiangtao; Liu, Shuwei; Toga, Arthur

2018-05-01

Numerous behavioral observations and brain function studies have demonstrated that neurological differences exist between East Asians and Westerners. However, the extent to which these factors relate to differences in brain structure is still not clear. As the basis of brain functions, the anatomical differences in brain structure play a primary and critical role in the origination of functional and behavior differences. To investigate the underlying differences in brain structure between the two cultural/ethnic groups, we conducted a comparative study on education-matched right-handed young male adults (age = 22-29 years) from two cohorts, Han Chinese (n = 45) and Caucasians (n = 45), using high-dimensional structural magnetic resonance imaging (MRI) data. Using two well-validated imaging analysis techniques, surface-based morphometry (SBM) and voxel-based morphometry (VBM), we performed a comprehensive vertex-wise morphometric analysis of the brain structures between Chinese and Caucasian cohorts. We identified consistent significant between-group differences in cortical thickness, volume, and surface area in the frontal, temporal, parietal, occipital, and insular lobes as well as the cingulate cortices. The SBM analyses revealed that compared with Caucasians, the Chinese population showed larger cortical structures in the temporal and cingulate regions, and smaller structural measures in the frontal and parietal cortices. The VBM data of the same sample was well-aligned with the SBM findings. Our findings systematically revealed comprehensive brain structural differences between young male Chinese and Caucasians, and provided new neuroanatomical insights to the behavioral and functional distinctions in the two cultural/ethnic populations. © 2018 Wiley Periodicals, Inc.

Lung cancer risk and consumption of vegetables and fruit: an evaluation based on a systematic review of epidemiological evidence from Japan.

PubMed

Wakai, Kenji; Matsuo, Keitaro; Nagata, Chisato; Mizoue, Tetsuya; Tanaka, Keitaro; Tsuji, Ichiro; Sasazuki, Shizuka; Shimazu, Taichi; Sawada, Norie; Inoue, Manami; Tsugane, Shoichiro

2011-05-01

Clinical trials of β-carotene supplementation and recent large-scale prospective studies have called into question the protective effects of vegetable and fruit consumption against lung cancer. To re-assess this issue, we reviewed data from Japanese epidemiological studies. Original data were obtained from searches of MEDLINE and the Japana Centra Revuo Medicina (Ichushi) database. The associations were assessed based on their magnitude and the strength of the evidence, together with their biological plausibility as previously evaluated by the International Agency for Research on Cancer. We identified six cohort studies and four case-control studies on the consumption of vegetables and/or fruit. We focused on fruit and green-yellow vegetables as food items, as they were included in more of the studies, and insufficient data were available on other types of vegetables. Among the three cohort and two case-control studies that reported on green-yellow vegetables, only one of each study type showed a weak inverse association between lung cancer risk and their consumption. Two of the four cohort studies and one (or possibly two) of the four case-control studies demonstrated a weak inverse correlation between lung cancer risk and fruit consumption. Meta-analysis for fruit consumption revealed a summary relative risk that was significantly smaller than unity. Our analysis of the Japanese epidemiological data showed that fruit consumption possibly decreased the risk of lung cancer, but found insufficient evidence of a link with vegetable consumption. Further prospective studies should assess the effects of consuming these food groups.

Body-Mass Index and Pancreatic Cancer Incidence: A Pooled Analysis of Nine Population-Based Cohort Studies With More Than 340,000 Japanese Subjects.

PubMed

Koyanagi, Yuriko N; Matsuo, Keitaro; Ito, Hidemi; Tamakoshi, Akiko; Sugawara, Yumi; Hidaka, Akihisa; Wada, Keiko; Oze, Isao; Kitamura, Yuri; Liu, Rong; Mizoue, Tetsuya; Sawada, Norie; Nagata, Chisato; Wakai, Kenji; Nakayama, Tomio; Sadakane, Atsuko; Tanaka, Keitaro; Inoue, Manami; Tsugane, Shoichiro; Sasazuki, Shizuka

2018-05-05

A high body mass index (BMI) has been proposed as an important risk factor for pancreatic cancer. However, this association of BMI with pancreatic cancer risk has not been confirmed in Asian populations. We evaluated the association between BMI (either at baseline or during early adulthood) and pancreatic cancer risk by conducting a pooled analysis of nine population-based prospective cohort studies in Japan with more than 340,000 subjects. Summary hazard ratios (HRs) were estimated by pooling study-specific HRs for unified BMI categories with a random-effects model. Among Japanese men, being obese at baseline was associated with a higher risk of pancreatic cancer incidence (≥30 kg/m 2 compared with 23 to <25 kg/m 2 , adjusted HR 1.71; 95% confidence interval [CI], 1.03-2.86). A J-shaped association between BMI during early adulthood and pancreatic cancer incidence was seen in men. In contrast, we observed no clear association among women, although there may be a positive linear association between BMI at baseline and the risk of pancreatic cancer (per 1 kg/m 2 , adjusted HR 1.02; 95% CI, 1.00-1.05). Pooling of data from cohort studies with a considerable number of Japanese subjects revealed a significant positive association between obesity and pancreatic cancer risk among men. This information indicates that strategies that effectively prevent obesity among men might lead to a reduced burden of pancreatic cancer, especially in Asian populations.

Risk of epilepsy in type 1 diabetes mellitus: a population-based cohort study.

PubMed

Chou, I-Ching; Wang, Chung-Hsing; Lin, Wei-De; Tsai, Fuu-Jen; Lin, Che-Chen; Kao, Chia-Hung

2016-06-01

Type 1 diabetes mellitus is a major public health problem of increasing global concern, with potential neurological complications. A possible association exists between type 1 diabetes and subsequent epilepsy. This study evaluated the relationship between type 1 diabetes and epilepsy in Taiwan. Claims data from the Taiwan National Health Insurance Research Database were used to conduct retrospective cohort analyses. The study cohort contained 2568 patients with type 1 diabetes, each of whom was frequency-matched by sex, urbanisation of residence area and index year with ten patients without type 1 diabetes. Cox proportional hazard regression analysis was conducted to estimate the effects of type 1 diabetes on epilepsy risk. In patients with type 1 diabetes, the risk of developing epilepsy was significantly higher than that in patients without type 1 diabetes (p < 0.0001 for logrank test). After adjustment for potential confounders, the type 1 diabetes cohort was 2.84 times as likely to develop epilepsy than the control cohort was (HR 2.84 [95% CI 2.11, 3.83]). Patients with type 1 diabetes are at an increased risk of developing epilepsy. Metabolic abnormalities of type 1 diabetes, such as hyperglycaemia and hypoglycaemia, may have a damaging effect on the central nervous system and be associated with significant long-term neurological sequelae. The causative factors between type 1 diabetes and the increased risk of epilepsy require further investigation.

Clinical effectiveness of a silicone foam dressing for the prevention of heel pressure ulcers in critically ill patients: Border II Trial.

PubMed

Santamaria, N; Gerdtz, M; Liu, W; Rakis, S; Sage, S; Ng, A W; Tudor, H; McCann, J; Vassiliou, T; Morrow, F; Smith, K; Knott, J; Liew, D

2015-08-01

Critically ill patients are at high risk of developing pressure ulcers (PU), with the sacrum and heels being highly susceptible to pressure injuries. The objective of our study was to evaluate the clinical effectiveness of a new multi-layer, self-adhesive soft silicone foam heel dressing to prevent PU development in trauma and critically ill patients in the intensive care unit (ICU). A cohort of critically ill patients were enrolled at the Royal Melbourne Hospital. Each patient had the multi-layer soft silicone foam dressing applied to each heel on admission to the emergency department. The dressings were retained with a tubular bandage for the duration of the patients' stay in the ICU. The skin under the dressings was examined daily and the dressings were replaced every three days. The comparator for our cohort study was the control group from the recently completed Border Trial. Of the 191 patients in the initial cohort, excluding deaths, loss to follow-up and transfers to another ward, 150 patients were included in the final analysis. There was no difference in key demographic or physiological variables between the cohorts, apart from a longer ICU length of stay for our current cohort. No PUs developed in any of our intervention cohort patients compared with 14 patients in the control cohort (n=152; p<0.001) who developed a total of 19 heel PUs. We conclude, based on our results, that the multi-layer soft silicone foam dressing under investigation was clinically effective in reducing ICU-acquired heel PUs. The findings also support previous research on the clinical effectiveness of multi-layer soft silicone foam dressings for PU prevention in the ICU.

Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts.

PubMed

Silventoinen, Karri; Jelenkovic, Aline; Latvala, Antti; Sund, Reijo; Yokoyama, Yoshie; Ullemar, Vilhelmina; Almqvist, Catarina; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth J F; Kandler, Christian; Honda, Chika; Inui, Fujio; Iwatani, Yoshinori; Watanabe, Mikio; Rebato, Esther; Stazi, Maria A; Fagnani, Corrado; Brescianini, Sonia; Hur, Yoon-Mi; Jeong, Hoe-Uk; Cutler, Tessa L; Hopper, John L; Busjahn, Andreas; Saudino, Kimberly J; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rose, Richard J; Koskenvuo, Markku; Heikkilä, Kauko; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Siribaddana, Sisira H; Hotopf, Matthew; Sumathipala, Athula; Rijsdijk, Fruhling; Sung, Joohon; Kim, Jina; Lee, Jooyeon; Lee, Sooji; Nelson, Tracy L; Whitfield, Keith E; Tan, Qihua; Zhang, Dongfeng; Llewellyn, Clare H; Fisher, Abigail; Burt, S Alexandra; Klump, Kelly L; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Medland, Sarah E; Martin, Nicholas G; Montgomery, Grant W; Magnusson, Patrik K E; Pedersen, Nancy L; Dahl Aslan, Anna K; Corley, Robin P; Huibregtse, Brooke M; Öncel, Sevgi Y; Aliev, Fazil; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Willemsen, Gonneke; Bartels, Meike; van Beijsterveldt, Catharina E M; Silberg, Judy L; Eaves, Lindon J; Maes, Hermine H; Harris, Jennifer R; Brandt, Ingunn; Nilsen, Thomas S; Rasmussen, Finn; Tynelius, Per; Baker, Laura A; Tuvblad, Catherine; Ordoñana, Juan R; Sánchez-Romera, Juan F; Colodro-Conde, Lucia; Gatz, Margaret; Butler, David A; Lichtenstein, Paul; Goldberg, Jack H; Harden, K Paige; Tucker-Drob, Elliot M; Duncan, Glen E; Buchwald, Dedra; Tarnoki, Adam D; Tarnoki, David L; Franz, Carol E; Kremen, William S; Lyons, Michael J; Maia, José A; Freitas, Duarte L; Turkheimer, Eric; Sørensen, Thorkild I A; Boomsma, Dorret I; Kaprio, Jaakko

2017-10-01

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

Cholecystectomy Reduces Recurrent Pancreatitis and Improves Survival After Endoscopic Sphincterotomy.

PubMed

Young, Shih-Hao; Peng, Yen-Ling; Lin, Xi-Hsuan; Chen, Yung-Tai; Luo, Jiing-Chyuan; Wang, Yen-Po; Hou, Ming-Chih; Lee, Fa-Yauh

2017-02-01

The aim of this study was to assess whether cholecystectomy can decrease the recurrent pancreatitis in the elderly patients who received endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) and successful clearance of bile duct (BD) stones after gallstone-related acute pancreatitis. We analyzed data from National Health Insurance Research Database of Taiwan. Elderly patients (age ≧70 years old) who had gallstone-related acute pancreatitis and underwent successful EST with BD stones clearance were eligible for enrollment. This nationwide, population-based, propensity score (PS)-matched cohort study involved two cohorts: (1) patients who underwent cholecystectomy after ERCP with BD stone clearance as study group and (2) those who adopted wait-and-see strategy (without cholecystectomy) after ERCP with BD stone clearance as control group. The primary and secondary endpoints were recurrent acute pancreatitis and all-cause mortality, respectively. During the study period, a total of 670 elderly patients (male 291, female 379) with a mean age of 79.1 was enrolled for analysis after PS matching. The incidence rate of recurrent acute pancreatitis was 12.39 per 1000 person-years in the cholecystectomy cohort and 23.94 per 1000 person-years in the PS-matched control cohort. The risk of recurrent acute pancreatitis was significantly lower in the cholecystectomy cohort (HR, 0.56; 95 % confidence interval [CI], 0.34-0.91; P = 0.021). The HR for all-cause mortality among the cholecystectomy cohort was 0.75 (95 % CI, 0.59-0.95; P = 0.016) compared with the control cohort. Cholecystectomy decreased the subsequent recurrent acute pancreatitis and the all-cause mortality in elderly patients with EST and clearance of BD stones after gallstone-related acute pancreatitis.

Comparison of rehospitalization rates and associated costs among patients with schizophrenia receiving paliperidone palmitate or oral antipsychotics.

PubMed

Lafeuille, Marie-Hélène; Grittner, Amanda Melina; Fortier, Jonathan; Muser, Erik; Fasteneau, John; Duh, Mei Sheng; Lefebvre, Patrick

2015-03-01

Comparative data on rehospitalization patterns and associated institutional costs after inpatient treatment with paliperidone palmitate or oral antipsychotic therapy are reported. A retrospective cohort study was conducted using discharge and billing records from a large hospital database. Selected clinical and cost outcomes were compared in a cohort of adult patients who received the long-acting antipsychotic paliperidone palmitate during a schizophrenia-related index hospital stay and a cohort of patients who received oral antipsychotic therapy during their index admission. Inverse probability-of-treatment weights based on propensity scores were used to reduce confounding. Rates of all-cause and schizophrenia-related rehospitalization and emergency room (ER) use in the two cohorts over periods of up to 12 months were analyzed using a multivariate Cox proportional hazard model. Institutional costs for the evaluated postdischarge events were compared via multivariate linear regression analysis. In the first 12 months after index hospital discharge, the risk of all-cause rehospitalization and ER use was significantly lower in the paliperidone palmitate cohort than in the oral antipsychotic cohort (hazard ratio, 0.61; 95% confidence interval [CI], 0.59-0.63; p < 0.0001); institutional costs during the first 6 months after discharge were significantly lower in the paliperidone palmitate cohort than in the comparator group (adjusted mean monthly cost difference -$404; 95% CI, -$781 to -$148; p < 0.0001). The use of paliperidone palmitate therapy during patients' index hospital admission for schizophrenia was associated with a reduced risk of hospital readmission or ER use and lower postdischarge institutional costs. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Predicting Early Mortality After Hip Fracture Surgery: The Hip Fracture Estimator of Mortality Amsterdam.

PubMed

Karres, Julian; Kieviet, Noera; Eerenberg, Jan-Peter; Vrouenraets, Bart C

2018-01-01

Early mortality after hip fracture surgery is high and preoperative risk assessment for the individual patient is challenging. A risk model could identify patients in need of more intensive perioperative care, provide insight in the prognosis, and allow for risk adjustment in audits. This study aimed to develop and validate a risk prediction model for 30-day mortality after hip fracture surgery: the Hip fracture Estimator of Mortality Amsterdam (HEMA). Data on 1050 consecutive patients undergoing hip fracture surgery between 2004 and 2010 were retrospectively collected and randomly split into a development cohort (746 patients) and validation cohort (304 patients). Logistic regression analysis was performed in the development cohort to determine risk factors for the HEMA. Discrimination and calibration were assessed in both cohorts using the area under the receiver operating characteristic curve (AUC), the Hosmer-Lemeshow goodness-of-fit test, and by stratification into low-, medium- and high-risk groups. Nine predictors for 30-day mortality were identified and used in the final model: age ≥85 years, in-hospital fracture, signs of malnutrition, myocardial infarction, congestive heart failure, current pneumonia, renal failure, malignancy, and serum urea >9 mmol/L. The HEMA showed good discrimination in the development cohort (AUC = 0.81) and the validation cohort (AUC = 0.79). The Hosmer-Lemeshow test indicated no lack of fit in either cohort (P > 0.05). The HEMA is based on preoperative variables and can be used to predict the risk of 30-day mortality after hip fracture surgery for the individual patient. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Incidence of fractures among epilepsy patients: a population-based retrospective cohort study in the General Practice Research Database.

PubMed

Souverein, Patrick C; Webb, David J; Petri, Hans; Weil, John; Van Staa, Tjeerd P; Egberts, Toine

2005-02-01

To compare the incidence of various fractures in a cohort of patients with epilepsy with a reference cohort of patients not having epilepsy. Patients were included in the epilepsy cohort if they had at least one diagnosis of epilepsy in their medical history and had sufficient evidence of "active" epilepsy (use of antiepileptic drugs, diagnoses) after the practice was included in the General Practice Research Database (GPRD). Two reference patients were sampled for each patient with epilepsy from the same practice. Primary outcome was the occurrence of any fracture during follow-up. Poisson regression analysis was used to estimate incidence density ratios (IDRs). The study population comprised 40,485 and 80,970 patients in the epilepsy and reference cohorts, respectively. The median duration of follow-up was approximately 3 years. The overall incidence rate in the epilepsy cohort was 241.9 per 10,000 person-years. This rate was about twice as high as that in reference cohort: age- and sex-adjusted IDR, 1.89 (95% CI, 1.81-1.98). When comparing IDRs among the different groups of fractures, the highest relative-risk estimate was found for hip and femur fractures (adjusted IDR, 2.79; 95% CI, 2.41-3.24). IDRs were consistently elevated across age and sex groups and across fracture subtypes. The overall risk of fractures was nearly twice as high among patients with epilepsy compared with the general population. The relative fracture risk was highest for hip and femur. Further study is necessary to elucidate whether this elevated risk is due to the disease, the use of antiepileptic drugs, or both.

Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia.

PubMed

Verhoeven, Virginie J M; Hysi, Pirro G; Wojciechowski, Robert; Fan, Qiao; Guggenheim, Jeremy A; Höhn, René; MacGregor, Stuart; Hewitt, Alex W; Nag, Abhishek; Cheng, Ching-Yu; Yonova-Doing, Ekaterina; Zhou, Xin; Ikram, M Kamran; Buitendijk, Gabriëlle H S; McMahon, George; Kemp, John P; Pourcain, Beate St; Simpson, Claire L; Mäkelä, Kari-Matti; Lehtimäki, Terho; Kähönen, Mika; Paterson, Andrew D; Hosseini, S Mohsen; Wong, Hoi Suen; Xu, Liang; Jonas, Jost B; Pärssinen, Olavi; Wedenoja, Juho; Yip, Shea Ping; Ho, Daniel W H; Pang, Chi Pui; Chen, Li Jia; Burdon, Kathryn P; Craig, Jamie E; Klein, Barbara E K; Klein, Ronald; Haller, Toomas; Metspalu, Andres; Khor, Chiea-Chuen; Tai, E-Shyong; Aung, Tin; Vithana, Eranga; Tay, Wan-Ting; Barathi, Veluchamy A; Chen, Peng; Li, Ruoying; Liao, Jiemin; Zheng, Yingfeng; Ong, Rick T; Döring, Angela; Evans, David M; Timpson, Nicholas J; Verkerk, Annemieke J M H; Meitinger, Thomas; Raitakari, Olli; Hawthorne, Felicia; Spector, Tim D; Karssen, Lennart C; Pirastu, Mario; Murgia, Federico; Ang, Wei; Mishra, Aniket; Montgomery, Grant W; Pennell, Craig E; Cumberland, Phillippa M; Cotlarciuc, Ioana; Mitchell, Paul; Wang, Jie Jin; Schache, Maria; Janmahasatian, Sarayut; Janmahasathian, Sarayut; Igo, Robert P; Lass, Jonathan H; Chew, Emily; Iyengar, Sudha K; Gorgels, Theo G M F; Rudan, Igor; Hayward, Caroline; Wright, Alan F; Polasek, Ozren; Vatavuk, Zoran; Wilson, James F; Fleck, Brian; Zeller, Tanja; Mirshahi, Alireza; Müller, Christian; Uitterlinden, André G; Rivadeneira, Fernando; Vingerling, Johannes R; Hofman, Albert; Oostra, Ben A; Amin, Najaf; Bergen, Arthur A B; Teo, Yik-Ying; Rahi, Jugnoo S; Vitart, Veronique; Williams, Cathy; Baird, Paul N; Wong, Tien-Yin; Oexle, Konrad; Pfeiffer, Norbert; Mackey, David A; Young, Terri L; van Duijn, Cornelia M; Saw, Seang-Mei; Bailey-Wilson, Joan E; Stambolian, Dwight; Klaver, Caroline C; Hammond, Christopher J

2013-03-01

Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

A simple algorithm for the identification of clinical COPD phenotypes.

PubMed

Burgel, Pierre-Régis; Paillasseur, Jean-Louis; Janssens, Wim; Piquet, Jacques; Ter Riet, Gerben; Garcia-Aymerich, Judith; Cosio, Borja; Bakke, Per; Puhan, Milo A; Langhammer, Arnulf; Alfageme, Inmaculada; Almagro, Pere; Ancochea, Julio; Celli, Bartolome R; Casanova, Ciro; de-Torres, Juan P; Decramer, Marc; Echazarreta, Andrés; Esteban, Cristobal; Gomez Punter, Rosa Mar; Han, MeiLan K; Johannessen, Ane; Kaiser, Bernhard; Lamprecht, Bernd; Lange, Peter; Leivseth, Linda; Marin, Jose M; Martin, Francis; Martinez-Camblor, Pablo; Miravitlles, Marc; Oga, Toru; Sofia Ramírez, Ana; Sin, Don D; Sobradillo, Patricia; Soler-Cataluña, Juan J; Turner, Alice M; Verdu Rivera, Francisco Javier; Soriano, Joan B; Roche, Nicolas

2017-11-01

This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses.Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative International Assessment (3CIA) initiative.Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated that the variables relevant for patient grouping differed markedly between patients with isolated respiratory disease (FEV 1 , dyspnoea grade) and those with multi-morbidity (dyspnoea grade, age, FEV 1 and body mass index). Application of this algorithm to the 3CIA cohorts confirmed that it identified subgroups of patients with different clinical characteristics, mortality rates (median, from 4% to 27%) and age at death (median, from 68 to 76 years).A simple algorithm, integrating respiratory characteristics and comorbidities, allowed the identification of clinically relevant COPD phenotypes. Copyright ©ERS 2017.

Identification of ageing-associated naturally occurring peptides in human urine

PubMed Central

Nkuipou-Kenfack, Esther; Bhat, Akshay; Klein, Julie; Jankowski, Vera; Mullen, William; Vlahou, Antonia; Dakna, Mohammed; Koeck, Thomas; Schanstra, Joost P.; Zürbig, Petra; Rudolph, Karl L.; Schumacher, Björn; Pich, Andreas; Mischak, Harald

2015-01-01

To assess normal and pathological peptidomic changes that may lead to an improved understanding of molecular mechanisms underlying ageing, urinary peptidomes of 1227 healthy and 10333 diseased individuals between 20 and 86 years of age were investigated. The diseases thereby comprised diabetes mellitus, renal and cardiovascular diseases. Using age as a continuous variable, 116 peptides were identified that significantly (p < 0.05; |ρ|≥0.2) correlated with age in the healthy cohort. The same approach was applied to the diseased cohort. Upon comparison of the peptide patterns of the two cohorts 112 common age-correlated peptides were identified. These 112 peptides predominantly originated from collagen, uromodulin and fibrinogen. While most fibrillar and basement membrane collagen fragments showed a decreased age-related excretion, uromodulin, beta-2-microglobulin and fibrinogen fragments showed an increase. Peptide-based in silico protease analysis was performed and 32 proteases, including matrix metalloproteinases and cathepsins, were predicted to be involved in ageing. Identified peptides, predicted proteases and patient information were combined in a systems biology pathway analysis to identify molecular pathways associated with normal and/or pathological ageing. While perturbations in collagen homeostasis, trafficking of toll-like receptors and endosomal pathways were commonly identified, degradation of insulin-like growth factor-binding proteins was uniquely identified in pathological ageing. PMID:26431327

Science Anxiety and Gender in Students Taking General Education Science Courses

NASA Astrophysics Data System (ADS)

Udo, M. K.; Ramsey, G. P.; Mallow, J. V.

2004-12-01

Earlier studies [Mallow, J. V. (1994). Gender-related science anxiety: A first binational study. Journal of Science Education and Technology 3: 227-238; Udo, M. K., Ramsey, G. P., Reynolds-Alpert, S., and Mallow, J. V. (2001). Does physics teaching affect gender-based science anxiety? Journal of Science Education and Technology 10: 237-247] of science anxiety in various student cohorts suggested that nonscience majors were highly science anxious (SA), regardless of what science courses they were taking. In this study, we investigated science anxiety in a cohort consisting mostly of nonscience majors taking general education science courses. Regression analysis shows that the leading predictors of science anxiety are (i) nonscience anxiety and (ii) gender, as they were for different cohorts in the earlier studies. We confirm earlier findings that females are more SA than males. Chi-square analysis of acute science anxiety shows an amplification of these differences. We found statistically significant levels of science anxiety in humanities and social science students of both genders, and gender differences in science anxiety, despite the fact that the students were all enrolled in general education science courses specifically designed for nonscience majors. We found acute levels of anxiety in several groups, especially education, nursing, and business majors. We describe specific interventions to alleviate science anxiety.

Retrospective database analysis of the impact of prior authorization for type 2 diabetes medications on health care costs in a Medicare Advantage Prescription Drug Plan population.

PubMed

Bergeson, Joette Gdovin; Worley, Karen; Louder, Anthony; Ward, Melea; Graham, John

2013-06-01

Health plans and pharmacy benefit managers have implemented utilization management strategies for newer type 2 diabetes mellitus (T2DM) medications to control pharmacy expenditures. Little is known about the impact of utilization management strategies on overall health care costs and subsequent use of T2DM medications among members who request, but do not receive, a T2DM medication requiring prior authorization (PA).  To examine the relationship between the receipt of a T2DM medication requiring PA, health care costs, and subsequent treatment for T2DM.  A retrospective cohort study using pharmacy, medical, and laboratory claims data was conducted among Medicare Advantage Prescription Drug plan members with a denied claim for a T2DM medication requiring PA (sitagliptin, a dipeptidyl peptidase-4 inhibitor [DPP-4i], and exenatide, an incretin mimetic) between January 1, 2008, and June 30, 2009. Subjects were required to have 12 months of continuous enrollment both before and after the index date. The entire study period was 24 months in duration, including a 12-month pre-index and 12-month post-index period. Three cohorts were identified: 1 that received a medication requiring PA (denied claim, subsequent fill) and 2 nonfilling control groups. Both control groups requested a medication requiring PA, as evidenced by the denied claim, but neither received the medication, either because the medication was not authorized or the member chose not to fill. Claims-based estimates were used to infer whether the individual likely met the criteria for PA, with 1 control group designated as having met the claims-based criteria (qualifying nonfilling cohort) and the other not having done so (nonqualifying nonfilling cohort.) The primary endpoint evaluated was the relationship between PA medication fill status and plan-paid costs (medical [including laboratory] and pharmacy) over the 12-month post-denial period, with generalized linear models adjusting for key covariates including demographics, concomitant medications, pre-index costs, pre-index adherence, and comorbidities. The secondary endpoint of T2DM medication use (post-denial) among the 2 nonfilling control groups was also evaluated.  There were 1,728 members identified who received medication for T2DM requiring PA (the received authorization cohort) and 2,373 who did not (606 qualifying nonfilling cohort; 1,767 nonqualifying nonfilling cohort.) Cohorts were similar with regard to age and gender, but the nonfilling cohort had more comorbidities. Total unadjusted plan-paid 12-month costs were lowest among the received authorization cohort ($11,739), slightly higher ($11,980) for the qualifying nonfilling cohort, and notably higher for the nonqualifying nonfilling cohort ($12,962), although no differences were statistically significant. After adjusting for key covariates, the difference between the nonqualifying nonfilling cohort ($11,980) and the received authorization cohort ($11,729) was statistically significant (P = 0.034). Large differences in plan-paid medical costs ($10,127 for the nonqualifying nonfilling cohort vs. $8,192 for the received authorization cohort) appeared to drive the overall cost totals and were significant in both the unadjusted (P = 0.005) and adjusted models (P  less than  0.001). Pharmacy costs were significantly lower for the nonqualifying nonfilling cohort in the adjusted model and for the qualifying nonfilling cohort in both models (all P  less than  0.001), but the lower pharmacy costs were not offset by the higher medical costs. In examining the use of medication for treatment of T2DM following the denied claim, 10.6% of the qualifying nonfilling cohort and 13.4% of the nonqualifying nonfilling cohort added another oral therapy, 10.2% and 5.8% added insulin, and 11.9% and 7.1% had treatment intensification, respectively. More than half (56.1%) of the qualifying nonfilling cohort, but only 32.1% of the nonqualifying nonfilling cohort, maintained current therapy.   This study found higher plan-paid health care costs (overall and medical alone) among members who requested a type 2 diabetes medication requiring PA, but never received it, compared with those who qualified for and received the requested medication. A notable number of individuals who were assumed to have met the criteria based on a claims-based equivalent, but who never received the medication, made no change to their current therapy. Failure of a member to take medication deemed necessary by his or her physician could translate to inadequate control of the diabetic condition and result in an excess of resource utilization and costs for treating the disease and associated comorbidities. In light of the present findings, health plans should consider not only the impact of utilization management strategies on reducing pharmacy costs, but the broader implication for overall health care costs and subsequent treatment patterns among members. 

Cost Analysis of a Novel Enzymatic Debriding Agent for Management of Burn Wounds.

PubMed

Giudice, Giuseppe; Filoni, Angela; Maggio, Giulio; Bonamonte, Domenico; Vestita, Michelangelo

2017-01-01

Introduction . Given its efficacy and safety, NexoBrid™ (NXB) has become part of our therapeutic options in burns treatment with satisfactory results. However, no cost analysis comparing NXB to the standard of care (SOC) has been carried out as of today. Aim . To assess the cost of treatment with NXB and compare it to the SOC cost. Methods . 20 patients with 14-22% of TBSA with an intermediate-deep thermal burn related injury were retrospectively and consecutively included. 10 of these patients were treated with the SOC, while the other 10 with NXB. The cost analysis was performed in accordance with the weighted average Italian Health Ministry DRGs and with Conferenza Stato/Regioni 2003 and the study by Tan et al. For each cost, 95% confidence intervals have been evaluated. Results . Considering the 10 patients treated with NXB, the overall savings (total net saving) amounted to 53300 euros. The confidence interval analysis confirmed the savings. Discussion . As shown by our preliminary results, significant savings are obtained with the use of NXB. The limit of our study is that it is based on Italian health care costs and assesses a relative small cohort of patients. Further studies on larger multinational cohorts are warranted.

Cost-effectiveness of the non-laboratory based Framingham algorithm in primary prevention of cardiovascular disease: A simulated analysis of a cohort of African American adults.

PubMed

Kariuki, Jacob K; Gona, Philimon; Leveille, Suzanne G; Stuart-Shor, Eileen M; Hayman, Laura L; Cromwell, Jerry

2018-06-01

The non-lab Framingham algorithm, which substitute body mass index for lipids in the laboratory based (lab-based) Framingham algorithm, has been validated among African Americans (AAs). However, its cost-effectiveness and economic tradeoffs have not been evaluated. This study examines the incremental cost-effectiveness ratio (ICER) of two cardiovascular disease (CVD) prevention programs guided by the non-lab versus lab-based Framingham algorithm. We simulated the World Health Organization CVD prevention guidelines on a cohort of 2690 AA participants in the Atherosclerosis Risk in Communities (ARIC) cohort. Costs were estimated using Medicare fee schedules (diagnostic tests, drugs & visits), Bureau of Labor Statistics (RN wages), and estimates for managing incident CVD events. Outcomes were assumed to be true positive cases detected at a data driven treatment threshold. Both algorithms had the best balance of sensitivity/specificity at the moderate risk threshold (>10% risk). Over 12years, 82% and 77% of 401 incident CVD events were accurately predicted via the non-lab and lab-based Framingham algorithms, respectively. There were 20 fewer false negative cases in the non-lab approach translating into over $900,000 in savings over 12years. The ICER was -$57,153 for every extra CVD event prevented when using the non-lab algorithm. The approach guided by the non-lab Framingham strategy dominated the lab-based approach with respect to both costs and predictive ability. Consequently, the non-lab Framingham algorithm could potentially provide a highly effective screening tool at lower cost to address the high burden of CVD especially among AA and in resource-constrained settings where lab tests are unavailable. Copyright © 2017 Elsevier Inc. All rights reserved.

Exposure enriched outcome dependent designs for longitudinal studies of gene-environment interaction.

PubMed

Sun, Zhichao; Mukherjee, Bhramar; Estes, Jason P; Vokonas, Pantel S; Park, Sung Kyun

2017-08-15

Joint effects of genetic and environmental factors have been increasingly recognized in the development of many complex human diseases. Despite the popularity of case-control and case-only designs, longitudinal cohort studies that can capture time-varying outcome and exposure information have long been recommended for gene-environment (G × E) interactions. To date, literature on sampling designs for longitudinal studies of G × E interaction is quite limited. We therefore consider designs that can prioritize a subsample of the existing cohort for retrospective genotyping on the basis of currently available outcome, exposure, and covariate data. In this work, we propose stratified sampling based on summaries of individual exposures and outcome trajectories and develop a full conditional likelihood approach for estimation that adjusts for the biased sample. We compare the performance of our proposed design and analysis with combinations of different sampling designs and estimation approaches via simulation. We observe that the full conditional likelihood provides improved estimates for the G × E interaction and joint exposure effects over uncorrected complete-case analysis, and the exposure enriched outcome trajectory dependent design outperforms other designs in terms of estimation efficiency and power for detection of the G × E interaction. We also illustrate our design and analysis using data from the Normative Aging Study, an ongoing longitudinal cohort study initiated by the Veterans Administration in 1963. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Cancer incidence and mortality in workers employed at a transformer manufacturing plant: update to a cohort study.

PubMed

Yassi, Annalee; Tate, Robert B; Routledge, Michael

2003-07-01

This study is an extension of a previously published analysis of cancer mortality in a transformer manufacturing plant where there had been extensive use of mineral oil transformer fluid. The objectives of the present study were to update the mortality analysis and include deaths for the past 6 years as well as to do an analysis of cancer incidence of the cohort. A cohort of 2,222 males working at a transformer manufacturing plant between 1946 and 1975 was constructed. Using a classical historical cohort study design, cancer incidence and mortality were determined through record linkage with Canadian provincial and national registries. The rates of cancer incidence and mortality experienced by this cohort were compared to that of the Canadian male population. A statistically significant increased risk of developing and dying of pancreatic cancer was found but not an increase in overall cancer mortality. This was consistent with the previous report from this group. Interestingly, the cohort demonstrated a statistically significant risk of overall cancer incidence and specific increased incidence of gallbladder cancer. This study contributes further evidence to the growing body of literature indicating the carcinogenic properties of mineral oils used in occupational settings, in particular those used prior to 1970s. Copyright 2003 Wiley-Liss, Inc.

Prognostic significance of NOD2/CARD15 variants in HLA-identical sibling hematopoietic stem cell transplantation: effect on long-term outcome is confirmed in 2 independent cohorts and may be modulated by the type of gastrointestinal decontamination.

PubMed

Holler, Ernst; Rogler, Gerhard; Brenmoehl, Julia; Hahn, Joachim; Herfarth, Hans; Greinix, Hildegard; Dickinson, Anne M; Socié, Gerard; Wolff, Daniel; Fischer, Gottfried; Jackson, Graham; Rocha, Vanderson; Steiner, Beate; Eissner, Guenther; Marienhagen, Jeorg; Schoelmerich, Juergen; Andreesen, Reinhard

2006-05-15

To assess the role of NOD2/CARD15 variants on the long-term outcome of allogeneic stem cell transplantation in a genetically homogeneous group, we extended our previous study (cohort I, n = 78) and typed DNA for NOD2/CARD15 single nucleotide polymorphisms (SNPs) from an additional 225 recipients and their HLA-identical sibling donors (cohort II) treated at four other European centers. Results of genotyping were compared with clinical outcome. The strong association of NOD2/CARD15 variants with transplantation-related mortality (TRM) was confirmed in univariate and multivariate analysis; TRM increased from 20% in cohort I/22% in cohort II in recipient/donor pairs without any NOD2/CARD15 variants to 47% in cohort I/32% in cohort II in the presence of one variant in either donor or recipient and further to 57% in cohort I/74% in cohort II in the presence of 2 or more variants (P < .002 in both cohorts). NOD2/CARD15 SNPs were not associated with relapse rate but had a strong impact on overall survival. In an analysis of center effects, the type of gastrointestinal decontamination was the only factor interfering with the prognostic significance of NOD2/CARD15 SNPs. Our data further support an interaction between gastrointestinal defense mechanisms, activation of the innate immune system, and specific transplant-related complications.

Screening for single nucleotide variants, small indels and exon deletions with a next-generation sequencing based gene panel approach for Usher syndrome

PubMed Central

Krawitz, Peter M; Schiska, Daniela; Krüger, Ulrike; Appelt, Sandra; Heinrich, Verena; Parkhomchuk, Dmitri; Timmermann, Bernd; Millan, Jose M; Robinson, Peter N; Mundlos, Stefan; Hecht, Jochen; Gross, Manfred

2014-01-01

Usher syndrome is an autosomal recessive disorder characterized both by deafness and blindness. For the three clinical subtypes of Usher syndrome causal mutations in altogether 12 genes and a modifier gene have been identified. Due to the genetic heterogeneity of Usher syndrome, the molecular analysis is predestined for a comprehensive and parallelized analysis of all known genes by next-generation sequencing (NGS) approaches. We describe here the targeted enrichment and deep sequencing for exons of Usher genes and compare the costs and workload of this approach compared to Sanger sequencing. We also present a bioinformatics analysis pipeline that allows us to detect single-nucleotide variants, short insertions and deletions, as well as copy number variations of one or more exons on the same sequence data. Additionally, we present a flexible in silico gene panel for the analysis of sequence variants, in which newly identified genes can easily be included. We applied this approach to a cohort of 44 Usher patients and detected biallelic pathogenic mutations in 35 individuals and monoallelic mutations in eight individuals of our cohort. Thirty-nine of the sequence variants, including two heterozygous deletions comprising several exons of USH2A, have not been reported so far. Our NGS-based approach allowed us to assess single-nucleotide variants, small indels, and whole exon deletions in a single test. The described diagnostic approach is fast and cost-effective with a high molecular diagnostic yield. PMID:25333064

Screening for single nucleotide variants, small indels and exon deletions with a next-generation sequencing based gene panel approach for Usher syndrome.

PubMed

Krawitz, Peter M; Schiska, Daniela; Krüger, Ulrike; Appelt, Sandra; Heinrich, Verena; Parkhomchuk, Dmitri; Timmermann, Bernd; Millan, Jose M; Robinson, Peter N; Mundlos, Stefan; Hecht, Jochen; Gross, Manfred

2014-09-01

Usher syndrome is an autosomal recessive disorder characterized both by deafness and blindness. For the three clinical subtypes of Usher syndrome causal mutations in altogether 12 genes and a modifier gene have been identified. Due to the genetic heterogeneity of Usher syndrome, the molecular analysis is predestined for a comprehensive and parallelized analysis of all known genes by next-generation sequencing (NGS) approaches. We describe here the targeted enrichment and deep sequencing for exons of Usher genes and compare the costs and workload of this approach compared to Sanger sequencing. We also present a bioinformatics analysis pipeline that allows us to detect single-nucleotide variants, short insertions and deletions, as well as copy number variations of one or more exons on the same sequence data. Additionally, we present a flexible in silico gene panel for the analysis of sequence variants, in which newly identified genes can easily be included. We applied this approach to a cohort of 44 Usher patients and detected biallelic pathogenic mutations in 35 individuals and monoallelic mutations in eight individuals of our cohort. Thirty-nine of the sequence variants, including two heterozygous deletions comprising several exons of USH2A, have not been reported so far. Our NGS-based approach allowed us to assess single-nucleotide variants, small indels, and whole exon deletions in a single test. The described diagnostic approach is fast and cost-effective with a high molecular diagnostic yield.

WE-FG-202-03: Quantitative CT-Based Analysis to Assess Lung Injury Following Proton Radiotherapy

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

Underwood, T; University College London, London; Grassberger, C

2016-06-15

Purpose: Relative to photon alternatives, the increased dose-conformity associated with proton therapy is expected to reduce the extent of radiation-induced lung toxicity. However, analysis of follow-up data is yet to be published in this area. In this study we retrospectively analyzed late-phase HU changes for proton therapy cohorts of chest wall and lung patients. Methods: From our institution’s register of patients treated using double-scattered protons, all chest wall and stereotactic lung cases (treated 2011–2012 and 2008–2014 respectively) were initially considered. Follow-up CT data were accessible for 10 chest wall cases (prescribed 50.4 GyRBE in 28 fractions) and 16 lung casesmore » (prescribed 42–50 GyRBE in 3–4 fractions). CT time-points ranged from 0.5–3.5 years post-treatment. Planning doses were recalculated using TOPAS Monte Carlo simulations and mapped onto the follow-up images using deformable registration. Excluding internal target volumes, changes in HU between each patient’s planning and follow-up CT(s) were evaluated for dose bins of 2–30 GyRBE (2 GyRBE increments). Results: Linear increases in HU per unit dose, with correlations statistically significant at the 1% level (one-sided Spearman’s rank test), were evident for all 10 chest wall cases and 14/16 lung cases. The mean changes in HU/Gy were: 1.76 (SD=0.73) for the chest wall cohort, and 1.40 (SD=0.87) for the lung cohort. The median scan times post treatment were 21 and 12 months respectively. All 26 patients developed solid consolidation (scar-like radiographic opacities) within the exposed lung(s). Conclusion: Analysis of follow-up CTs revealed statistically significant correlations in HU-change/dose for two proton cohorts (lung and chest wall). Quantitatively, the late-phase changes we report broadly match published photon data. Further analysis of such radiographic changes, particularly via matched cohort studies drawing upon consistent imaging protocols, could play an important role in elucidating inter-modality differences and provide insight into proton RBE for lung injury. Tracy Underwood gratefully acknowledges the support of the European Commission under an FP7 Marie Curie International Outgoing Fellowship for Career Development (#630064). This work was also funded under U19 grant CA 021239 (PI: Delaney).« less

Diet based on the Japanese Food Guide Spinning Top and subsequent mortality among men and women in a general Japanese population.

PubMed

Oba, Shino; Nagata, Chisato; Nakamura, Kozue; Fujii, Kaori; Kawachi, Toshiaki; Takatsuka, Naoyoshi; Shimizu, Hiroyuki

2009-09-01

The Japanese Food Guide Spinning Top was developed by the Japanese Ministry of Health, Labor, and Welfare and the Ministry of Agriculture, Forestry, and Fishery to promote healthful diets. Adherence to the Japanese Food Guide Spinning Top was evaluated in terms of future mortality in a prospective cohort study. A prospective cohort study among men and women in a general Japanese population. The cohort consisted of 13,355 men and 15,724 women residing in Takayama, Japan, in 1992. At baseline, a food frequency questionnaire was administered, and adherence to the food guide was measured based on consuming the recommended number of servings of grains, vegetables, fish and meat, milk, and fruits, as well as total daily energy intake and energy from snacks and alcoholic beverages. Higher scores indicated better adherence to the recommendations on a scale of 0 to 70. Based on data obtained from the Office of the National Vital Statistics, deaths occurring among members of the cohort were prospectively noted from 1992 to 1999. To assess the magnitude of association of adherence scores with subsequent mortality, a Cox proportional hazard model was applied to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Among women, the adherence score was significantly associated with a lower risk of mortality from all causes (comparing highest and lowest quartiles of the score, HR 0.78, 95% CI 0.65 to 0.94, P for trend 0.01) in a multivariate analysis; noncardiovascular, noncancer causes (HR 0.69, 95% CI 0.50 to 0.96, P for trend 0.04) and cardiovascular disease (HR 0.76, 95% CI 0.56 to 1.04, P for trend0.05). No statistically significant association was observed between the adherence score and mortality among men. The results suggest that diets based on the food guide have the benefit of reducing future mortality in women.

The Omega-3 Index and relative risk for coronary heart disease mortality: Estimation from 10 cohort studies.

PubMed

Harris, William S; Del Gobbo, Liana; Tintle, Nathan L

2017-07-01

A recent 19-cohort meta-analysis examined the relationships between biomarkers of omega-3 fatty acids and risk for coronary heart disease (CHD). That study did not, however, report hazard ratios (HRs) specifically as a function of erythrocyte eicosapentaenoic (EPA) plus docosahexaenoic (DHA) levels, a metric called the Omega-3 Index in which EPA + DHA content is expressed as a percent of total fatty acids. The Omega-3 Index has been used in several recent studies and is a validated biomarker of omega-3 fatty acid tissue levels, but additional data are needed to confirm (or refute) the originally-proposed clinical cut-points of <4% (higher risk) and 8%-12% (lower risk). The present study was therefore undertaken using published data from this meta-analysis to estimate HRs per 1-SD increase in the Omega-3 Index and median quintile values for this metric across 10 of the cohorts for which the needed data were available. The overall mean (SD) for the Omega-3 Index in these 10 cohort studies was 6.1% (2.1%), and the HR for a 1-SD increase was 0.85 (95% confidence interval, 0.80-0.91). Median quintile 1 and 5 levels were 4.2% vs. 8.3%, respectively. Based on these values, we estimate that risk for fatal CHD would have been reduced by about 30% moving from an Omega-3 Index of 4%-8%. These findings support the use of <4% and >8% as reasonable therapeutic targets for the Omega-3 Index. Copyright © 2017 Elsevier B.V. All rights reserved.

External validation of the CAPRA-S score to predict biochemical recurrence, metastasis and mortality after radical prostatectomy in a European cohort.

PubMed

Tilki, Derya; Mandel, Philipp; Schlomm, Thorsten; Chun, Felix K-H; Tennstedt, Pierre; Pehrke, Dirk; Haese, Alexander; Huland, Hartwig; Graefen, Markus; Salomon, Georg

2015-06-01

The CAPRA-S score predicts prostate cancer recurrence based on pathological information from radical prostatectomy. To our knowledge CAPRA-S has never been externally validated in a European cohort. We independently validated CAPRA-S in a single institution European database. The study cohort comprised 14,532 patients treated with radical prostatectomy between January 1992 and August 2012. Prediction of biochemical recurrence, metastasis and cancer specific mortality by CAPRA-S was assessed by Kaplan-Meier analysis and the c-index. CAPRA-S performance to predict biochemical recurrence was evaluated by calibration plot and decision curve analysis. Median followup was 50.8 months (IQR 25.0-96.0). Biochemical recurrence developed in 20.3% of men at a median of 21.2 months (IQR 7.7-44.9). When stratifying patients by CAPRA-S risk group, estimated 5-year biochemical recurrence-free survival was 91.4%, 70.4% and 29.3% in the low, intermediate and high risk groups, respectively. The CAPRA-S c-index to predict biochemical recurrence, metastasis and cancer specific mortality was 0.80, 0.85 and 0.88, respectively. Metastasis developed in 417 men and 196 men died of prostate cancer. The CAPRA-S score was accurate when applied in a European study cohort. It predicted biochemical recurrence, metastasis and cancer specific mortality after radical prostatectomy with a c-index of greater than 0.80. The score can be valuable in regard to decision making for adjuvant therapy. Copyright © 2015. Published by Elsevier Inc.

[Ethical considerations in genomic cohort study].

PubMed

Choi, Eun Kyung; Kim, Ock-Joo

2007-03-01

During the last decade, genomic cohort study has been developed in many countries by linking health data and genetic data in stored samples. Genomic cohort study is expected to find key genetic components that contribute to common diseases, thereby promising great advance in genome medicine. While many countries endeavor to build biobank systems, biobank-based genome research has raised important ethical concerns including genetic privacy, confidentiality, discrimination, and informed consent. Informed consent for biobank poses an important question: whether true informed consent is possible in population-based genomic cohort research where the nature of future studies is unforeseeable when consent is obtained. Due to the sensitive character of genetic information, protecting privacy and keeping confidentiality become important topics. To minimize ethical problems and achieve scientific goals to its maximum degree, each country strives to build population-based genomic cohort research project, by organizing public consultation, trying public and expert consensus in research, and providing safeguards to protect privacy and confidentiality.

Selecting, Adapting, and Implementing Evidence-based Interventions in Rural Settings: An Analysis of 70 Community Examples.

PubMed

Smith, Tina Anderson; Adimu, Tanisa Foxworth; Martinez, Amanda Phillips; Minyard, Karen

2016-01-01

This paper explores how communities translate evidence-based and promising health practices to rural contexts. A descriptive, qualitative analysis was conducted using data from 70 grantees funded by the Federal Office of Rural Health Policy to implement evidence-based health practices in rural settings. Findings were organized using The Interactive Systems Framework for Dissemination and Implementation. Grantees broadly interpreted evidence-based and promising practices, resulting in the implementation of a patchwork of health-related interventions that fell along a spectrum of evidentiary rigor. The cohort faced common challenges translating recognized practices into rural community settings and reported making deliberate modifications to original models as a result. Opportunities for building a more robust rural health evidence base include investments to incentivize evidence-based programming in rural settings; rural-specific research and theory-building; translation of existing evidence using a rural lens; technical assistance to support rural innovation; and prioritization of evaluation locally.

Changing attitudes toward aging policy in the United States during the 1980s and 1990s: a cohort analysis.

PubMed

Silverstein, M; Angelelli, J J; Parrott, T M

2001-01-01

This research assessed how the attitudes of Americans toward government programs that serve older people changed between the mid-1980s and late 1990s and how much of the shift was dueto intracohort change and how much was due to cohort replacement. Data come from three nationally representative cross-sectional samples, surveyed by telephone in 1986 (N = 1.209), 1990 (N = 1,500), and 1997 (N = 1,559). Attitudes of Americans have become less supportive of expanding entitlement programs for older people and more supportive of cutting their costs and benefits. Between 1986 and 1997, most cohorts, particularly older adults, grew more in favor of maintaining Social Security benefit levels but less in favor of expanding them. Young adults tended to be driving the societal shift in attitudes toward decreasing benefits. Intercohort change was more important than cohort replacement in this process. Analyses of change in 2 attitude domains between 1990 and 1997 revealed that the general population felt less strongly that older people are entitled to benefits and expressed greater opposition to the associated costs. However, young adults moderated their concerns about costs as they got older, although the young adults in the cohort replacing them had become more critical of the principle of entitlement. These findings enhance the understanding of the roles that historical conditions and aging play in shaping the attitudes of adult cohorts toward public programs for older citizens. Discrepant findings based on the intercohort change in younger age groups are reconciled by differentiating maturation effects from period effects on impressionable youth.

Vitamin B12 intake and status and cognitive function in elderly people.

PubMed

Doets, Esmée L; van Wijngaarden, Janneke P; Szczecińska, Anna; Dullemeijer, Carla; Souverein, Olga W; Dhonukshe-Rutten, Rosalie A M; Cavelaars, Adrienne E J M; van 't Veer, Pieter; Brzozowska, Anna; de Groot, Lisette C P G M

2013-01-01

Current recommendations on vitamin B12 intake vary from 1.4 to 3.0 μg per day and are based on the amount needed for maintenance of hematologic status or on the amount needed to compensate obligatory losses. This systematic review evaluates whether the relation between vitamin B12 intake and cognitive function should be considered for underpinning vitamin B12 recommendations in the future. The authors summarized dose-response evidence from randomized controlled trials and prospective cohort studies on the relation of vitamin B12 intake and status with cognitive function in adults and elderly people. Two randomized controlled trials and 6 cohort studies showed no association or inconsistent associations between vitamin B12 intake and cognitive function. Random-effects meta-analysis showed that serum/plasma vitamin B12 (50 pmol/L) was not associated with risk of dementia (4 cohort studies), global cognition z scores (4 cohort studies), or memory z scores (4 cohort studies). Although dose-response evidence on sensitive markers of vitamin B12 status (methylmalonic acid and holotranscobalamin) was scarce, 4 of 5 cohort studies reported significant associations with risk of dementia, Alzheimer's disease, or global cognition. Current evidence on the relation between vitamin B12 intake or status and cognitive function is not sufficient for consideration in the development of vitamin B12 recommendations. Further studies should consider the selection of sensitive markers of vitamin B12 status. © The Author 2012. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Developing and Refining the Taiwan Birth Cohort Study (TBCS): Five Years of Experience

ERIC Educational Resources Information Center

Lung, For-Wey; Chiang, Tung-Liang; Lin, Shio-Jean; Shu, Bih-Ching; Lee, Meng-Chih

2011-01-01

The Taiwan Birth Cohort Study (TBCS) is the first nationwide birth cohort database in Asia designed to establish national norms of children's development. Several challenges during database development and data analysis were identified. Challenges include sampling methods, instrument development and statistical approach to missing data. The…

Explaining Changes in the Patterns of Black Suicide in the United States From 1981 to 2002: An Age, Cohort, and Period Analysis

PubMed Central

Joe, Sean

2009-01-01

To explore the different trends of suicide incidence among Blacks and possible contributing factors, the current study compared national epidemiologic data of suicide in the United States from 1981 to 2002. For the first time, period and birth-cohort effects on the incidence trends of Black suicide were evaluated using an age-period-cohort analysis. Cohort effects were found for males and females, suggesting that younger generations of Blacks are at higher risk. If younger cohorts carry their increased suicide risk into later life, then the recent decline in Black suicide rates will be reversed. The results of the current study are only interpretable in terms of group-level characteristics and population suicide rates and not individual-level characteristics. The possible explanation and the implications for prevention and future research are discussed. PMID:19759855

Multicenter validation study of a transplantation-specific cytogenetics grouping scheme for patients with myelodysplastic syndromes.

PubMed

Armand, P; Deeg, H J; Kim, H T; Lee, H; Armistead, P; de Lima, M; Gupta, V; Soiffer, R J

2010-05-01

Cytogenetics is an important prognostic factor for patients with myelodysplastic syndromes (MDS). However, existing cytogenetics grouping schemes are based on patients treated with supportive care, and may not be optimal for patients undergoing allo-SCT. We proposed earlier an SCT-specific cytogenetics grouping scheme for patients with MDS and AML arising from MDS, based on an analysis of patients transplanted at the Dana-Farber Cancer Institute/Brigham and Women's Hospital. Under this scheme, abnormalities of chromosome 7 and complex karyotype are considered adverse risk, whereas all others are considered standard risk. In this retrospective study, we validated this scheme on an independent multicenter cohort of 546 patients. Adverse cytogenetics was the strongest prognostic factor for outcome in this cohort. The 4-year relapse-free survival and OS were 42 and 46%, respectively, in the standard-risk group, vs 21 and 23% in the adverse group (P<0.0001 for both comparisons). This grouping scheme retained its prognostic significance irrespective of patient age, disease type, earlier leukemogenic therapy and conditioning intensity. Therapy-related disease was not associated with increased mortality in this cohort, after taking cytogenetics into account. We propose that this SCT-specific cytogenetics grouping scheme be used for patients with MDS or AML arising from MDS who are considering or undergoing SCT.

Chocolate consumption and risk of atrial fibrillation: Two cohort studies and a meta-analysis.

PubMed

Larsson, Susanna C; Drca, Nikola; Jensen-Urstad, Mats; Wolk, Alicja

2018-01-01

Chocolate consumption has been inconsistently associated with risk of atrial fibrillation (AF). We investigated the association between chocolate consumption and risk of AF in Swedish adults from two cohort studies and conducted a meta-analysis to summarize available evidence from cohort studies on this topic. Our study population comprised 40,009 men from the Cohort of Swedish Men and 32,486 women from the Swedish Mammography Cohort. Incident AF cases were ascertained through linkage with the Swedish National Patient Register. Published cohort studies of chocolate consumption in relation to risk of AF were identified by a PubMed search through September 14, 2017. During a mean follow-up of 14.6 years, AF was diagnosed in 9978 Swedish men and women. Compared with non-consumers, the multivariable hazard ratio of AF for those in the highest category of chocolate consumption (≥3-4 servings/week) was 0.96 (95% CI 0.88-1.04). In a random-effects meta-analysis of 5 cohort studies, including 180,454 participants and 16,356 AF cases, the hazard ratios of AF were 0.97 (95% CI 0.94-1.01) per 2 servings/week increase in chocolate consumption and 0.96 (95% CI 0.90-1.03) for the highest versus lowest category of chocolate consumption. Available data provide no evidence of an association of chocolate consumption with risk of AF. Copyright © 2017 Elsevier Inc. All rights reserved.

Mortality study of civilian employees exposed to contaminated drinking water at USMC Base Camp Lejeune: a retrospective cohort study

PubMed Central

2014-01-01

Background Two drinking water systems at U.S. Marine Corps Base Camp Lejeune, North Carolina were contaminated with solvents during 1950s-1985. Methods We conducted a retrospective cohort mortality study of 4,647 civilian, full-time workers employed at Camp Lejeune during 1973–1985 and potentially exposed to contaminated drinking water. We selected a comparison cohort of 4,690 Camp Pendleton workers employed during 1973–1985 and unexposed to contaminated drinking water. Mortality follow-up period was 1979-2008. Cause-specific standardized mortality ratios utilized U.S. age-, sex-, race-, and calendar period-specific mortality rates as reference. We used survival analysis to compare mortality rates between Camp Lejeune and Camp Pendleton workers and assess the effects of estimated cumulative contaminant exposures within the Camp Lejeune cohort. Ground water contaminant fate/transport and distribution system models provided monthly estimated contaminant levels in drinking water serving workplaces at Camp Lejeune. The confidence interval (CI) indicated precision of effect estimates. Results Compared to Camp Pendleton, Camp Lejeune workers had mortality hazard ratios (HRs) >1.50 for kidney cancer (HR = 1.92, 95% CI: 0.58, 6.34), leukemias (HR = 1.59, 95% CI: 0.66, 3.84), multiple myeloma (HR = 1.84, 95% CI: 0.45, 7.58), rectal cancer (HR = 1.65, 95% CI: 0.36, 7.44), oral cavity cancers (HR = 1.93, 95% CI: 0.34, 10.81), and Parkinson’s disease (HR = 3.13, 95% CI: 0.76, 12.81). Within the Camp Lejeune cohort, monotonic exposure-response relationships were observed for leukemia and vinyl chloride and PCE, with mortality HRs at the high exposure category of 1.72 (95% CI: 0.33, 8.83) and 1.82 (95% CI: 0.36, 9.32), respectively. Cumulative exposures were above the median for most deaths from cancers of the kidney, esophagus, rectum, prostate, and Parkinson’s disease, but small numbers precluded evaluation of exposure-response relationships. Conclusion The study found elevated HRs in the Camp Lejeune cohort for several causes of death including cancers of the kidney, rectum, oral cavity, leukemias, multiple myeloma, and Parkinson’s disease. Only 14% of the Camp Lejeune cohort died by end of follow-up, producing small numbers of cause-specific deaths and wide CIs. Additional follow-up would be necessary to comprehensively assess drinking water exposure effects at the base. PMID:25115749

Evaluation of mortality among marines and navy personnel exposed to contaminated drinking water at USMC base Camp Lejeune: a retrospective cohort study.

PubMed

Bove, Frank J; Ruckart, Perri Zeitz; Maslia, Morris; Larson, Theodore C

2014-02-19

Two drinking water systems at U.S. Marine Corps Base Camp Lejeune, North Carolina were contaminated with solvents during 1950s-1985. We conducted a retrospective cohort mortality study of Marine and Naval personnel who began service during 1975-1985 and were stationed at Camp Lejeune or Camp Pendleton, California during this period. Camp Pendleton's drinking water was uncontaminated. Mortality follow-up was 1979-2008. Standardized Mortality Ratios were calculated using U.S. mortality rates as reference. We used survival analysis to compare mortality rates between Camp Lejeune (N = 154,932) and Camp Pendleton (N = 154,969) cohorts and assess effects of cumulative exposures to contaminants within the Camp Lejeune cohort. Models estimated monthly contaminant levels at residences. Confidence intervals (CIs) indicated precision of effect estimates. There were 8,964 and 9,365 deaths respectively, in the Camp Lejeune and Camp Pendleton cohorts. Compared to Camp Pendleton, Camp Lejeune had elevated mortality hazard ratios (HRs) for all cancers (HR = 1.10, 95% CI: 1.00, 1.20), kidney cancer (HR = 1.35, 95% CI: 0.84, 2.16), liver cancer (HR = 1.42, 95% CI: 0.92, 2.20), esophageal cancer (HR = 1.43 95% CI: 0.85, 2.38), cervical cancer (HR = 1.33, 95% CI: 0.24, 7.32), Hodgkin lymphoma (HR = 1.47, 95% CI: 0.71, 3.06), and multiple myeloma (HR = 1.68, 95% CI: 0.76, 3.72). Within the Camp Lejeune cohort, monotonic categorical cumulative exposure trends were observed for kidney cancer and total contaminants (HR, high cumulative exposure = 1.54, 95% CI: 0.63, 3.75; log10 β = 0.06, 95% CI: -0.05, 0.17), Hodgkin lymphoma and trichloroethylene (HR, high cumulative exposure = 1.97, 95% CI: 0.55, 7.03; β = 0.00005, 95% CI: -0.00003, 0.00013) and benzene (HR, high cumulative exposure = 1.94, 95% CI: 0.54, 6.95; β = 0.00203, 95% CI: -0.00339, 0.00745). Amyotrophic Lateral Sclerosis (ALS) had HR = 2.21 (95% CI: 0.71, 6.86) at high cumulative vinyl chloride exposure but a non-monotonic exposure-response relationship (β = 0.0011, 95% CI: 0.0002, 0.0020). The study found elevated HRs at Camp Lejeune for several causes of death including cancers of the kidney, liver, esophagus, cervix, multiple myeloma, Hodgkin lymphoma and ALS. CIs were wide for most HRs. Because <6% of the cohort had died, long-term follow-up would be necessary to comprehensively assess effects of drinking water exposures at the base.

Quality of care received and patient-reported regret in prostate cancer: Analysis of a population-based prospective cohort.

PubMed

Holmes, Jordan A; Bensen, Jeannette T; Mohler, James L; Song, Lixin; Mishel, Merle H; Chen, Ronald C

2017-01-01

Meeting quality of care standards in oncology is recognized as important by physicians, professional organizations, and payers. Data from a population-based cohort of patients with prostate cancer were used to examine whether receipt of care was consistent with published consensus metrics and whether receiving high-quality care was associated with less patient-reported treatment decisional regret. Patients with incident prostate cancer were enrolled in collaboration with the North Carolina Central Cancer Registry, with an oversampling of minority patients. Medical record abstraction was used to determine whether participants received high-quality care based on 5 standards: 1) discussion of all treatment options; 2) complete workup (prostate-specific antigen, Gleason grade, and clinical stage); 3) low-risk participants did not undergo a bone scan; 4) high-risk participants treated with radiotherapy (RT) received androgen deprivation therapy; and 5) participants treated with RT received conformal or intensity-modulated RT. Treatment decisional regret was assessed using a validated instrument. A total of 804 participants were analyzed. Overall, 66% of African American and 73% of white participants received care that met all standards (P = .03); this racial difference was confirmed by multivariable analysis. Care that included "discussion of all treatment options" was found to be associated with less patient-reported regret on univariable analysis (P = .03) and multivariable analysis (odds ratio, 0.59; 95% confidence interval, 0.37-0.95). The majority of participants received high-quality care, but racial disparity existed. Participants who discussed all treatment options appeared to have less treatment decisional regret. To the authors' knowledge, this is the first study to demonstrate an association between a quality of care metric and patient-reported outcome. Cancer 2017;138-143. © 2016 American Cancer Society. © 2016 American Cancer Society.

Clinical framework for next generation sequencing based analysis of treatment predictive mutations and multiplexed gene fusion detection in non-small cell lung cancer

PubMed Central

Levéen, Per; Brunnström, Hans; Reuterswärd, Christel; Holm, Karolina; Jönsson, Mats; Annersten, Karin; Rosengren, Frida; Jirström, Karin; Kosieradzki, Jaroslaw; Ek, Lars; Borg, Åke; Planck, Maria; Jönsson, Göran; Staaf, Johan

2017-01-01

Precision medicine requires accurate multi-gene clinical diagnostics. We describe the implementation of an Illumina TruSight Tumor (TST) clinical NGS diagnostic framework and parallel validation of a NanoString RNA-based ALK, RET, and ROS1 gene fusion assay for combined analysis of treatment predictive alterations in non-small cell lung cancer (NSCLC) in a regional healthcare region of Sweden (Scandinavia). The TST panel was clinically validated in 81 tumors (99% hotspot mutation concordance), after which 533 consecutive NSCLCs were collected during one-year of routine clinical analysis in the healthcare region (˜90% advanced stage patients). The NanoString assay was evaluated in 169 of 533 cases. In the 533-sample cohort 79% had 1-2 variants, 12% >2 variants and 9% no detected variants. Ten gene fusions (five ALK, three RET, two ROS1) were detected in 135 successfully analyzed cases (80% analysis success rate). No ALK or ROS1 FISH fusion positive case was missed by the NanoString assay. Stratification of the 533-sample cohort based on actionable alterations in 11 oncogenes revealed that 66% of adenocarcinomas, 13% of squamous carcinoma (SqCC) and 56% of NSCLC not otherwise specified harbored ≥1 alteration. In adenocarcinoma, 10.6% of patients (50.3% if including KRAS) could potentially be eligible for emerging therapeutics, in addition to the 15.3% of patients eligible for standard EGFR or ALK inhibitors. For squamous carcinoma corresponding proportions were 4.4% (11.1% with KRAS) vs 2.2%. In conclusion, multiplexed NGS and gene fusion analyses are feasible in NSCLC for clinical diagnostics, identifying notable proportions of patients potentially eligible for emerging molecular therapeutics. PMID:28415793

[Mortality in the tire plant workers].

PubMed

Wilczyńska, U; Szadkowska-Stańczyk, I; Szeszenia-Dabrowska, N; Sobala, W; Strzelecka, A

2000-01-01

This paper describes a cohort study of the mortality among workers employed in one of Polish tyre plants. The scope of the study was limited to the analysis of mortality from main disease categories. Mortality from particular cancer sites will be discussed in a separate publication. The cohort comprised 17,747 workers (11,660 men and 6,087 women) employed during the years 1950-95 for at least three months in the tyre plant. As of 31 December 1995, the follow-up of the cohort was completed. A detailed analysis of mortality by causes was carried out using standardised mortality ratio (SMR) calculated by the person-years method. The general population of Poland was used as the reference. The results indicated general mortality significantly lower in the cohort (men: SMR = 72; women: SMR = 62), than in the reference population. The number of observed deaths from main disease categories was also lower than those expected. The analysis by specific causes revealed significant excess of deaths, due to hypertensive disease among men (36 deaths, SMR = 142; 95% CI: 99-197). SMRs were also calculated in sub-cohorts identified by activities performed (preparatory works: production of tyres and inner tubes; maintenance; storage; others). General mortality in sub-cohorts was similar to that in the total cohort. After analysis by causes of death, some non-significant excess mortality could be observed. It was very small or it applied only to single cases of death. Excess mortality from hypertensive disease in male maintenance workers (21 deaths, SMR = 262; 95% CI: 162-400) was the only exception. The absence of adverse health effects pronounced by significant excess mortality should be attributed to a relatively short period of exposure among the majority of the followed-up workers (over 58% of workers in the cohort employed in the plant for a period shorter than five years) and to their young age. Almost 56% of workers in the cohort were born in the 1950s or later which means that at the end of the follow-up they were not older than 45 years. In order to complete the final mortality assessment the follow-up should continue.

Toward standardized reporting for a cohort study on functioning: The Swiss Spinal Cord Injury Cohort Study.

PubMed

Prodinger, Birgit; Ballert, Carolina S; Brach, Mirjam; Brinkhof, Martin W G; Cieza, Alarcos; Hug, Kerstin; Jordan, Xavier; Post, Marcel W M; Scheel-Sailer, Anke; Schubert, Martin; Tennant, Alan; Stucki, Gerold

2016-02-01

Functioning is an important outcome to measure in cohort studies. Clear and operational outcomes are needed to judge the quality of a cohort study. This paper outlines guiding principles for reporting functioning in cohort studies and addresses some outstanding issues. Principles of how to standardize reporting of data from a cohort study on functioning, by deriving scores that are most useful for further statistical analysis and reporting, are outlined. The Swiss Spinal Cord Injury Cohort Study Community Survey serves as a case in point to provide a practical application of these principles. Development of reporting scores must be conceptually coherent and metrically sound. The International Classification of Functioning, Disability and Health (ICF) can serve as the frame of reference for this, with its categories serving as reference units for reporting. To derive a score for further statistical analysis and reporting, items measuring a single latent trait must be invariant across groups. The Rasch measurement model is well suited to test these assumptions. Our approach is a valuable guide for researchers and clinicians, as it fosters comparability of data, strengthens the comprehensiveness of scope, and provides invariant, interval-scaled data for further statistical analyses of functioning.

Real-time web-based assessment of total population risk of future emergency department utilization: statewide prospective active case finding study.

PubMed

Hu, Zhongkai; Jin, Bo; Shin, Andrew Y; Zhu, Chunqing; Zhao, Yifan; Hao, Shiying; Zheng, Le; Fu, Changlin; Wen, Qiaojun; Ji, Jun; Li, Zhen; Wang, Yong; Zheng, Xiaolin; Dai, Dorothy; Culver, Devore S; Alfreds, Shaun T; Rogow, Todd; Stearns, Frank; Sylvester, Karl G; Widen, Eric; Ling, Xuefeng B

2015-01-13

An easily accessible real-time Web-based utility to assess patient risks of future emergency department (ED) visits can help the health care provider guide the allocation of resources to better manage higher-risk patient populations and thereby reduce unnecessary use of EDs. Our main objective was to develop a Health Information Exchange-based, next 6-month ED risk surveillance system in the state of Maine. Data on electronic medical record (EMR) encounters integrated by HealthInfoNet (HIN), Maine's Health Information Exchange, were used to develop the Web-based surveillance system for a population ED future 6-month risk prediction. To model, a retrospective cohort of 829,641 patients with comprehensive clinical histories from January 1 to December 31, 2012 was used for training and then tested with a prospective cohort of 875,979 patients from July 1, 2012, to June 30, 2013. The multivariate statistical analysis identified 101 variables predictive of future defined 6-month risk of ED visit: 4 age groups, history of 8 different encounter types, history of 17 primary and 8 secondary diagnoses, 8 specific chronic diseases, 28 laboratory test results, history of 3 radiographic tests, and history of 25 outpatient prescription medications. The c-statistics for the retrospective and prospective cohorts were 0.739 and 0.732 respectively. Integration of our method into the HIN secure statewide data system in real time prospectively validated its performance. Cluster analysis in both the retrospective and prospective analyses revealed discrete subpopulations of high-risk patients, grouped around multiple "anchoring" demographics and chronic conditions. With the Web-based population risk-monitoring enterprise dashboards, the effectiveness of the active case finding algorithm has been validated by clinicians and caregivers in Maine. The active case finding model and associated real-time Web-based app were designed to track the evolving nature of total population risk, in a longitudinal manner, for ED visits across all payers, all diseases, and all age groups. Therefore, providers can implement targeted care management strategies to the patient subgroups with similar patterns of clinical histories, driving the delivery of more efficient and effective health care interventions. To the best of our knowledge, this prospectively validated EMR-based, Web-based tool is the first one to allow real-time total population risk assessment for statewide ED visits.

Assessing the order of magnitude of outcomes in single-arm cohorts through systematic comparison with corresponding cohorts: An example from the AMOS study

PubMed Central

Hamre, Harald J; Glockmann, Anja; Tröger, Wilfried; Kienle, Gunver S; Kiene, Helmut

2008-01-01

Background When a therapy has been evaluated in the first clinical study, the outcome is often compared descriptively to outcomes in corresponding cohorts receiving other treatments. Such comparisons are often limited to selected studies, and often mix different outcomes and follow-up periods. Here we give an example of a systematic comparison to all cohorts with identical outcomes and follow-up periods. Methods The therapy to be compared (anthroposophic medicine, a complementary therapy system) had been evaluated in one single-arm cohort study: the Anthroposophic Medicine Outcomes Study (AMOS). The five largest AMOS diagnosis groups (A-cohorts: asthma, depression, low back pain, migraine, neck pain) were compared to all retrievable corresponding cohorts (C-cohorts) receiving other therapies with identical outcomes (SF-36 scales or summary measures) and identical follow-up periods (3, 6 or 12 months). Between-group differences (pre-post difference in an A-cohort minus pre-post difference in the respective C-cohort) were divided with the standard deviation (SD) of the baseline score of the A-cohort. Results A-cohorts (5 cohorts with 392 patients) were similar to C-cohorts (84 cohorts with 16,167 patients) regarding age, disease duration, baseline affection and follow-up rates. A-cohorts had ≥ 0.50 SD larger improvements than C-cohorts in 13.5% (70/517) of comparisons; improvements of the same order of magnitude (small or minimal differences: -0.49 to 0.49 SD) were found in 80.1% of comparisons; and C-cohorts had ≥ 0.50 SD larger improvements than A-cohorts in 6.4% of comparisons. Analyses stratified by diagnosis had similar results. Sensitivity analyses, restricting the comparisons to C-cohorts with similar study design (observational studies), setting (primary care) or interventions (drugs, physical therapies, mixed), or restricting comparisons to SF-36 scales with small baseline differences between A- and C-cohorts (-0.49 to 0.49 SD) also had similar results. Conclusion In this descriptive analysis, anthroposophic therapy was associated with SF-36 improvements largely of the same order of magnitude as improvements following other treatments. Although these non-concurrent comparisons cannot assess comparative effectiveness, they suggest that improvements in health status following anthroposophic therapy can be clinically meaningful. The analysis also demonstrates the value of a systematic approach when comparing a therapy cohort to corresponding therapy cohorts. PMID:18366683

Developing and validating a novel metabolic tumor volume risk stratification system for supplementing non-small cell lung cancer staging.

PubMed

Pu, Yonglin; Zhang, James X; Liu, Haiyan; Appelbaum, Daniel; Meng, Jianfeng; Penney, Bill C

2018-06-07

We hypothesized that whole-body metabolic tumor volume (MTVwb) could be used to supplement non-small cell lung cancer (NSCLC) staging due to its independent prognostic value. The goal of this study was to develop and validate a novel MTVwb risk stratification system to supplement NSCLC staging. We performed an IRB-approved retrospective review of 935 patients with NSCLC and FDG-avid tumor divided into modeling and validation cohorts based on the type of PET/CT scanner used for imaging. In addition, sensitivity analysis was conducted by dividing the patient population into two randomized cohorts. Cox regression and Kaplan-Meier survival analyses were performed to determine the prognostic value of the MTVwb risk stratification system. The cut-off values (10.0, 53.4 and 155.0 mL) between the MTVwb quartiles of the modeling cohort were applied to both the modeling and validation cohorts to determine each patient's MTVwb risk stratum. The survival analyses showed that a lower MTVwb risk stratum was associated with better overall survival (all p < 0.01), independent of TNM stage together with other clinical prognostic factors, and the discriminatory power of the MTVwb risk stratification system, as measured by Gönen and Heller's concordance index, was not significantly different from that of TNM stage in both cohorts. Also, the prognostic value of the MTVwb risk stratum was robust in the two randomized cohorts. The discordance rate between the MTVwb risk stratum and TNM stage or substage was 45.1% in the modeling cohort and 50.3% in the validation cohort. This study developed and validated a novel MTVwb risk stratification system, which has prognostic value independent of the TNM stage and other clinical prognostic factors in NSCLC, suggesting that it could be used for further NSCLC pretreatment assessment and for refining treatment decisions in individual patients.

Differentials and income-related inequalities in maternal depression during the first two years after childbirth: birth cohort studies from Brazil and the UK.

PubMed

Matijasevich, Alicia; Golding, Jean; Smith, George Davey; Santos, Iná S; Barros, Aluísio Jd; Victora, Cesar G

2009-06-05

Depression is a prevalent health problem among women during the childbearing years. To obtain a more accurate global picture of maternal postnatal depression, studies that explore maternal depression with comparable measurements are needed. The aims of the study are: (1) to compare the prevalence of maternal depression in the first and second year postpartum between a UK and Brazilian birth cohort study; (2) to explore the extent to which variations in the rates were explained by maternal and infant characteristics, and (3) to investigate income-related inequalities in maternal depression after childbirth in both settings. Population-based birth cohort studies were carried out in Avon, UK in 1991 (ALSPAC) and in the city of Pelotas, Brazil in 2004, where 13 798 and 4109 women were analysed, respectively. Self-completion questionnaires were used in the ALSPAC study while questionnaires completed by interviewers were used in the Pelotas cohort study. Three repeated measures of maternal depression were obtained using the Edinburgh Postnatal Depression Scale in the first and second year after delivery in each cohort. Unadjusted and adjusted analyses were carried out. The Relative index of Inequality was used for the analysis of income-relate inequalities so that results were comparable between cohorts. At both the second and third time assessments, the likelihood of being depressed was higher among women from the Pelotas cohort study. These differences were not completely explained by differences in maternal and infant characteristics. Income-related inequalities in maternal depression after childbirth were high and of similar magnitude in both cohort studies at the three time assessments. The burden of maternal depression after childbirth varies between and within populations. Strategies to reduce income-related inequalities in maternal depression should be targeted to low-income women in both developed and developing countries.

Age-period-cohort analysis of infectious disease mortality in urban-rural China, 1990-2010.

PubMed

Li, Zhi; Wang, Peigang; Gao, Ge; Xu, Chunling; Chen, Xinguang

2016-03-31

Although a number of studies on infectious disease trends in China exist, these studies have not distinguished the age, period, and cohort effects simultaneously. Here, we analyze infectious disease mortality trends among urban and rural residents in China and distinguish the age, period, and cohort effects simultaneously. Infectious disease mortality rates (1990-2010) of urban and rural residents (5-84 years old) were obtained from the China Health Statistical Yearbook and analyzed with an age-period-cohort (APC) model based on Intrinsic Estimator (IE). Infectious disease mortality is relatively high at age group 5-9, reaches a minimum in adolescence (age group 10-19), then rises with age, with the growth rate gradually slowing down from approximately age 75. From 1990 to 2010, except for a slight rise among urban residents from 2000 to 2005, the mortality of Chinese residents experienced a substantial decline, though at a slower pace from 2005 to 2010. In contrast to the urban residents, rural residents experienced a rapid decline in mortality during 2000 to 2005. The mortality gap between urban and rural residents substantially narrowed during this period. Overall, later birth cohorts experienced lower infectious disease mortality risk. From the 1906-1910 to the 1941-1945 birth cohorts, the decrease of mortality among urban residents was significantly faster than that of subsequent birth cohorts and rural counterparts. With the rapid aging of the Chinese population, the prevention and control of infectious disease in elderly people will present greater challenges. From 1990 to 2010, the infectious disease mortality of Chinese residents and the urban-rural disparity have experienced substantial declines. However, the re-emergence of previously prevalent diseases and the emergence of new infectious diseases created new challenges. It is necessary to further strengthen screening, immunization, and treatment for the elderly and for older cohorts at high risk.

Modeling the fiscal costs and benefits of alternative treatment strategies in the United Kingdom for chronic hepatitis C.

PubMed

Connolly, Mark P; Kotsopoulos, Nikos; Ustianowski, Andrew

2018-01-01

Hepatitis C (HCV) infection causes substantial direct health costs, but also impacts broader societal and governmental costs, such as tax revenue and social protection benefits. This study investigated the broader fiscal costs and benefits of curative interventions for chronic Hepatitis C (CHC) that allow individuals to avoid long-term HCV attributed health conditions. A prospective cohort model, assessing the long-term fiscal consequences of policy decisions, was developed for HCV infected individuals, following the generational accounting analytic framework that combines age-specific lifetime gross taxes paid and governmental transfers received (i.e. healthcare and social support costs). The analysis assessed the burden of a theoretical cohort of untreated HCV infected patients with the alternative of treating these patients with a highly efficacious curative intervention (ledipasvir/sofosbuvir [LDV/SOF]). It also compared treating patients at all fibrosis stages (Stages F0-F4) compared to late treatment (Stage F4). Based on projected lifetime work activity and taxes paid, the treated cohort paid an additional £5,900 per patient compared to the untreated cohort. Lifetime government disability costs of £97,555 and £125,359 per patient for treated cohort vs no treatment cohort were estimated, respectively. Lifetime direct healthcare costs in the treated cohort were £32,235, compared to non-treated cohort of £26,424, with an incremental healthcare costs increase of £5,901 per patient. The benefit cost ratio (BCR) of total government benefits and savings relative to government treatment costs (including LDV/SOF) ranged from 1.8-5.6. Treating patients early resulted in 77% less disability costs, 43% lower healthcare costs, and 33% higher tax revenue. The ability to cure Hepatitis C offers considerable fiscal benefits beyond direct medical costs and savings attributed to reduced disability costs, public allowances, and improved tax revenue. Changes in parameters, such as productivity, wage growth, and tax rates, can influence the conclusions described here.

The cuticular hydrocarbons of the giant soil-burrowing cockroach Macropanesthia rhinoceros saussure (Blattodea: Blaberidae: Geoscapheinae): analysis with respect to age, sex and location.

PubMed

Brown, W V; Rose, H A; Lacey, M J; Wright, K

2000-11-01

The cuticular hydrocarbons of a widespread species of soil-burrowing cockroach, Macropanesthia rhinoceros, have been sampled from most of its known geographical locations. Analysis of extracts from individual insects has enabled a study of differences within a population as well as among geographical locations. In the case of M. rhinoceros, except for newly hatched first-instar nymphs, variations in hydrocarbon composition among individuals of different cohorts of M. rhinoceros, based on age and sex, are no greater than those among individuals of a single cohort. Geographical populations of this species are variable in hydrocarbon composition unless they occur within a few kilometres of each other. A few populations showed very different hydrocarbon patterns but, in the absence of any correlating biological differences, it is uncertain whether this signifies the presence of otherwise unrecognizable sibling species or just extreme examples of the geographical variation characteristic of this group of insects.

The Research Implications of Prostate Specific Antigen Registry Errors: Data from the Veterans Health Administration.

PubMed

Guo, David P; Thomas, I-Chun; Mittakanti, Harsha R; Shelton, Jeremy B; Makarov, Danil V; Skolarus, Ted A; Cooperberg, Mathew R; Sonn, Geoffrey A; Chung, Benjamin I; Brooks, James D; Leppert, John T

2018-04-06

We sought to characterize the effects of prostate specific antigen registry errors on clinical research by comparing cohorts based on cancer registry prostate specific antigen values with those based directly on results in the electronic health record. We defined sample cohorts of men with prostate cancer using data from the VHA (Veterans Health Administration), including those with a prostate specific antigen value less than 4.0, 4.0 to 10.0, 10.0 to 20.0 and 20.0 to 98.0 ng/ml, respectively. We compared the composition of each cohort and overall patient survival when using PSA values from the VACCR (Veteran Affairs Central Cancer Registry) vs the gold standard electronic health record laboratory file results. There was limited agreement among cohorts when defined by cancer registry PSA values vs the laboratory file of the electronic health record. The least agreement of 58% was seen in patients with PSA less than 4.0 ng/ml and greatest agreement of 89% was noted among patients with PSA between 4.0 and 10.0 ng/ml. In each cohort patients assigned to a cohort based only on the cancer registry PSA value had significantly different overall survival when compared with patients assigned based on registry and laboratory file PSA values. Cohorts based exclusively on cancer registry PSA values may have high rates of misclassification that can introduce concerning differences in key characteristics and result in measurable differences in clinical outcomes. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Low-Dose Aspirin Use Does Not Increase Survival in 2 Independent Population-Based Cohorts of Patients With Esophageal or Gastric Cancer.

PubMed

Spence, Andrew D; Busby, John; Johnston, Brian T; Baron, John A; Hughes, Carmel M; Coleman, Helen G; Cardwell, Chris R

2018-03-01

Preclinical studies have shown aspirin to have anticancer properties and epidemiologic studies have associated aspirin use with longer survival times of patients with cancer. We studied 2 large cohorts to determine the association between aspirin use and cancer-specific mortality in patients with esophageal or gastric cancer. We performed a population-based study using cohorts of patients newly diagnosed with esophageal or gastric cancer, identified from cancer registries in England from 1998 through 2012 and the Scottish Cancer Registry from 2009 through 2012. Low-dose aspirin prescriptions were identified from linkages to the United Kingdom Clinical Research Practice Datalink in England and the Prescribing Information System in Scotland. Deaths were identified from linkage to national mortality records, with follow-up until September 2015 in England and January 2015 in Scotland. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by low-dose aspirin use after adjusting for potential confounders. Meta-analysis was used to pool results across the 2 cohorts. The combined English and Scottish cohorts contained 4654 patients with esophageal cancer and 3833 patients with gastric cancer, including 3240 and 2392 cancer-specific deaths, respectively. The proportions surviving 1 year, based on cancer-specific mortality, were similar in aspirin users vs non-users after diagnosis with esophageal cancer (48% vs 50% in England and 49% vs 46% in Scotland, respectively) or gastric cancer (58% vs 57% in England and 59% vs 55% in Scotland, respectively). There was no association between postdiagnosis use of low-dose aspirin and cancer-specific mortality among patients with esophageal cancer (pooled adjusted HR, 0.98; 95% CI, 0.89-1.09) or gastric cancer (pooled adjusted HR, 0.96; 95% CI, 0.85-1.08). Long-term aspirin use was not associated with cancer-specific mortality after diagnosis of esophageal cancer (pooled adjusted HR, 1.03; 95% CI, 0.85-1.25) or gastric cancer (pooled adjusted HR, 1.06; 95% CI, 0.85-1.32). In analyses of 2 large independent cohorts in the United Kingdom, low-dose aspirin usage was not associated with increased survival of patients diagnosed with esophageal or gastric cancer. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Clinical inquiries. What test is the best for diagnosing infectious mononucleosis?

PubMed

Bell, Amy Trelease; Fortune, Barbara; Sheeler, Robert

2006-09-01

Tests for antibodies to Epstein-Barr viral capsid antigen or Epstein-Barr nuclear antigen are the most sensitive, are highly specific, and are also the most expensive for diagnosing infectious mononucleosis (strength of recommendation [SOR]: C, based on validating cohort study). Heterophile antibody tests have similar specificity and are cheaper, but are less sensitive in children or in adults during the early days of the illness (SOR: C, based on validating cohort study). The polymerase chain reaction assay for Epstein-Barr virus DNA is more sensitive than the heterophile antibody test in children, is highly specific, but is also expensive (SOR: C, based on validating cohort study). The percentages of atypical lymphocytes and total lymphocytes on a complete blood count provide another specific and moderately sensitive, yet inexpensive, test (SOR: C, based on validating cohort study).

A single pre-operative antibiotic dose is as effective as continued antibiotic prophylaxis in implant-based breast reconstruction: A matched cohort study.

PubMed

Townley, William A; Baluch, Narges; Bagher, Shaghayegh; Maass, Saskia W M C; O'Neill, Anne; Zhong, Toni; Hofer, Stefan O P

2015-05-01

Infections following implant-based breast reconstruction can lead to devastating consequences. There is currently no consensus on the need for post-operative antibiotics in preventing immediate infection. This study compared two different methods of infection prevention in this group of patients. A retrospective matched cohort study was performed on consecutive women undergoing implant-based breast reconstruction at University Health Network, Toronto (November 2008-December 2012). All patients received a single pre-operative intravenous antibiotic dose. Group A received minimal interventions and Group B underwent maximal prophylactic measures. Patient (age, smoking, diabetes, co-morbidities), oncologic and procedural variables (timing and laterality) were collected. Univariate and multivariate logistic regression were performed to compare outcomes between the two groups. Two hundred and eight patients underwent 647 implant procedures. After matching the two treatment groups by BMI, 94 patients in each treatment group yielding a total of 605 implant procedures were selected for analysis. The two groups were comparable in terms of patient and disease variables. Post-operative wound infection was similar in Group A (n = 11, 12%) compared with Group B (n = 9, 10%; p = 0.8). Univariate analysis revealed only pre-operative radiotherapy to be associated with the development of infection (0.004). Controlling for the effect of radiotherapy, multivariate analysis demonstrated that there was no statistically significant difference between the two methods for infection prevention. Our findings suggest that a single pre-operative dose of intravenous antibiotics is equally as effective as continued antibiotic prophylaxis in preventing immediate infection in patients undergoing implant-based breast reconstructions. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized clinical trials.

PubMed

Kabbinavar, Fairooz F; Hurwitz, Herbert I; Yi, Jing; Sarkar, Somnath; Rosen, Oliver

2009-01-10

Colorectal cancer (CRC) occurs predominantly in older persons. To provide more statistical power to assess risk/benefit in older patients, we examined the clinical benefit of bevacizumab (BV) plus fluorouracil-based chemotherapy in first-line metastatic CRC (mCRC) treatment in patients aged > or = 65 years, using data pooled from two placebo-controlled studies. Pooled efficacy data for 439 patients > or = 65 years old randomized to BV plus chemotherapy (n = 218) or placebo plus chemotherapy (n = 221) in study 1 and study 2 were retrospectively analyzed on an intent-to-treat basis for overall survival (OS), progression-free survival (PFS), and objective response. Safety analysis was based on reports of targeted adverse events in treated patients. Median OS with BV plus chemotherapy was 19.3 v 14.3 months with placebo plus chemotherapy (hazard ratio [HR] = 0.70; 95% CI, 0.55 to 0.90; P = .006). Patients treated with BV plus chemotherapy had a median PFS of 9.2 v 6.2 months for placebo plus chemotherapy patients (HR = 0.52; 95% CI, 0.40 to 0.67; P < .0001). The objective response rate was 34.4% with BV plus chemotherapy versus 29.0% with placebo plus chemotherapy (difference not statistically significant). Rates of BV-associated adverse events in the pooled BV plus chemotherapy group were consistent with those reported in the overall populations for the two studies. Analysis of pooled patient cohorts age >/= 65 years from two similar trials in mCRC indicates that adding bevacizumab to fluorouracil-based chemotherapy improved OS and PFS, similar to the benefits in younger patients. Also, the risks of treatment do not seem to exceed those in younger patients with mCRC.

Comprehensive gene- and pathway-based analysis of depressive symptoms in older adults.

PubMed

Nho, Kwangsik; Ramanan, Vijay K; Horgusluoglu, Emrin; Kim, Sungeun; Inlow, Mark H; Risacher, Shannon L; McDonald, Brenna C; Farlow, Martin R; Foroud, Tatiana M; Gao, Sujuan; Callahan, Christopher M; Hendrie, Hugh C; Niculescu, Alexander B; Saykin, Andrew J

2015-01-01

Depressive symptoms are common in older adults and are particularly prevalent in those with or at elevated risk for dementia. Although the heritability of depression is estimated to be substantial, single nucleotide polymorphism-based genome-wide association studies of depressive symptoms have had limited success. In this study, we performed genome-wide gene- and pathway-based analyses of depressive symptom burden. Study participants included non-Hispanic Caucasian subjects (n = 6,884) from three independent cohorts, the Alzheimer's Disease Neuroimaging Initiative (ADNI), the Health and Retirement Study (HRS), and the Indiana Memory and Aging Study (IMAS). Gene-based meta-analysis identified genome-wide significant associations (ANGPT4 and FAM110A, q-value = 0.026; GRM7-AS3 and LRFN5, q-value = 0.042). Pathway analysis revealed enrichment of association in 105 pathways, including multiple pathways related to ERK/MAPK signaling, GSK3 signaling in bipolar disorder, cell development, and immune activation and inflammation. GRM7, ANGPT4, and LRFN5 have been previously implicated in psychiatric disorders, including the GRM7 region displaying association with major depressive disorder. The ERK/MAPK signaling pathway is a known target of antidepressant drugs and has important roles in neuronal plasticity, and GSK3 signaling has been previously implicated in Alzheimer's disease and as a promising therapeutic target for depression. Our results warrant further investigation in independent and larger cohorts and add to the growing understanding of the genetics and pathobiology of depressive symptoms in aging and neurodegenerative disorders. In particular, the genes and pathways demonstrating association with depressive symptoms may be potential therapeutic targets for these symptoms in older adults.

A Progressive Assessment Strategy Improves Student Learning and Perceived Course Quality in Undergraduate Physiology

ERIC Educational Resources Information Center

Saint, D. A.; Horton, D.; Yool, A.; Elliott, A.

2015-01-01

In 2010, second-year physiology (n = 165) had a traditional single 3-h end-of-semester exam. To provide diagnostic feedback earlier, for students enrolled in 2011 (n = 128), we incorporated an in-class exam at 3 wk in addition to the final exam. Based on initial analysis and positive student comments, for the 2012 cohort (n = 148), we expanded…

Relationship between Gross Motor Capacity and Daily-Life Mobility in Children with Cerebral Palsy

ERIC Educational Resources Information Center

Smits, Dirk-Wouter; Gorter, Jan Willem; Ketelaar, Marjolijn; van Schie, Petra Em; Dallmeijer, Annet J.; Lindeman, Eline; Jongmans, Marian J.

2010-01-01

Aim: The aim of this study was to examine the relationship between gross motor capacity and daily-life mobility in children with cerebral palsy (CP) and to explore the moderation of this relationship by the severity of CP. Method: Cross-sectional analysis in a cohort study with a clinic-based sample of children with CP (n=116; 76 males, 40…

Public access to New Hampshire state waters: a comparison of three cohorts of residents across three distinct geographic

Treesearch

Kim Pawlawski; Robert A. Robertson; Laura Pfister

2003-01-01

This study was intended to provide New Hampshire agencies with a better understanding of public access-related demand information. Through an analysis of three groups of New Hampshire residents based upon geographic location and length of residency, important issues and attitudes were identified from all over the State. The results of this study will assist in policy-...

Long-Term Effects of Native Hawaiian Students' Early Academic Achievement under the No Child Left Behind Legislation: A Multilevel Cohort Analysis

ERIC Educational Resources Information Center

Singh, J. Malkeet

2011-01-01

The focus of the No Child Left Behind (NCLB) Legislation is to close the achievement gaps due to disadvantages based on minority status, socio-economic status, special education (SPED) or Limited English Proficiency (LEP). Poverty and culture have been consistently reported to have an impact on academic achievement. However, there have been few…

Risk of Autism Associated with General Anesthesia during Cesarean Delivery: A Population-Based Birth-Cohort Analysis

ERIC Educational Resources Information Center

Chien, Li-Nien; Lin, Hsiu-Chen; Shao, Yu-Hsuan Joni; Chiou, Shu-Ti; Chiou, Hung-Yi

2015-01-01

The rates of Cesarean delivery (C-section) have risen to >30 % in numerous countries. Increased risk of autism has been shown in neonates delivered by C-section. This study examined the incidence of autism in neonates delivered vaginally, by C-section with regional anesthesia (RA), and by C-section with general anesthesia (GA) to evaluate the…

Genome-wide scan in Hispanics highlights candidate loci for brain white matter hyperintensities

PubMed Central

Beecham, Ashley; Dong, Chuanhui; Wright, Clinton B.; Dueker, Nicole; Brickman, Adam M.; Wang, Liyong; DeCarli, Charles; Blanton, Susan H.; Rundek, Tatjana; Mayeux, Richard

2017-01-01

Objective: To investigate genetic variants influencing white matter hyperintensities (WMHs) in the understudied Hispanic population. Methods: Using 6.8 million single nucleotide polymorphisms (SNPs), we conducted a genome-wide association study (GWAS) to identify SNPs associated with WMH volume (WMHV) in 922 Hispanics who underwent brain MRI as a cross-section of 2 community-based cohorts in the Northern Manhattan Study and the Washington Heights–Inwood Columbia Aging Project. Multiple linear modeling with PLINK was performed to examine the additive genetic effects on ln(WMHV) after controlling for age, sex, total intracranial volume, and principal components of ancestry. Gene-based tests of association were performed using VEGAS. Replication was performed in independent samples of Europeans, African Americans, and Asians. Results: From the SNP analysis, a total of 17 independent SNPs in 7 genes had suggestive evidence of association with WMHV in Hispanics (p < 1 × 10−5) and 5 genes from the gene-based analysis with p < 1 × 10−3. One SNP (rs9957475 in GATA6) and 1 gene (UBE2C) demonstrated evidence of association (p < 0.05) in the African American sample. Four SNPs with p < 1 × 10−5 were shown to affect binding of SPI1 using RegulomeDB. Conclusions: This GWAS of 2 community-based Hispanic cohorts revealed several novel WMH-associated genetic variants. Further replication is needed in independent Hispanic samples to validate these suggestive associations, and fine mapping is needed to pinpoint causal variants. PMID:28975155

Reference-based phasing using the Haplotype Reference Consortium panel.

PubMed

Loh, Po-Ru; Danecek, Petr; Palamara, Pier Francesco; Fuchsberger, Christian; A Reshef, Yakir; K Finucane, Hilary; Schoenherr, Sebastian; Forer, Lukas; McCarthy, Shane; Abecasis, Goncalo R; Durbin, Richard; L Price, Alkes

2016-11-01

Haplotype phasing is a fundamental problem in medical and population genetics. Phasing is generally performed via statistical phasing in a genotyped cohort, an approach that can yield high accuracy in very large cohorts but attains lower accuracy in smaller cohorts. Here we instead explore the paradigm of reference-based phasing. We introduce a new phasing algorithm, Eagle2, that attains high accuracy across a broad range of cohort sizes by efficiently leveraging information from large external reference panels (such as the Haplotype Reference Consortium; HRC) using a new data structure based on the positional Burrows-Wheeler transform. We demonstrate that Eagle2 attains a ∼20× speedup and ∼10% increase in accuracy compared to reference-based phasing using SHAPEIT2. On European-ancestry samples, Eagle2 with the HRC panel achieves >2× the accuracy of 1000 Genomes-based phasing. Eagle2 is open source and freely available for HRC-based phasing via the Sanger Imputation Service and the Michigan Imputation Server.

Blood pressure at age 60-65 versus age 70-75 and vascular dementia: a population based observational study.

PubMed

Peng, Mingkai; Chen, Guanmin; Tang, Karen L; Quan, Hude; Smith, Eric E; Faris, Peter; Hachinski, Vladimir; Campbell, Norm R C

2017-10-27

Vascular dementia (VaD) is the second most common form of dementia. However, there were mixed evidences about the association between blood pressure (BP) and risk of VaD in midlife and late life and limited evidence on the association between pulse pressure and VaD. This is a population-based observational study. 265,897 individuals with at least one BP measurement between the ages of 60 to 65 years and 211,116 individuals with at least one BP measurement between the ages of 70 to 75 years were extracted from The Health Improvement Network in United Kingdom. Blood pressures were categorized into four groups: normal, prehypertension, stage 1 hypertension, and stage 2 hypertension. Cases of VaD were identified from the recorded clinical diagnoses. Multivariable survival analysis was used to adjust other confounders and competing risk of death. All the analysis were stratified based on antihypertensive drug use status. Multiple imputation was used to fill in missing values. After accounting for the competing risk of death and adjustment for potential confounders, there was an association between higher BP levels in the age 60-65 cohort with the risk of developing VaD (hazard ratio [HR] 1.53 (95% confidence interval: 1.04, 2.25) for prehypertension, 1.90 (1.30, 2.78) for stage 1 hypertension, and 2.19 (1.48, 3.26) for stage 2 hypertension) in the untreated group. There was no statistically significant association between BP levels and VaD in the treated group in the age 60-65 cohort and age 70-75 cohort. Analysis on Pulse Pressure (PP) stratified by blood pressure level showed that PP was not independently associated with VaD. High BP between the ages of 60 to 65 years is a significant risk for VaD in late midlife. Greater efforts should be placed on early diagnosis of hypertension and tight control of BP for hypertensive patients for the prevention of VaD.

Noninvasive Classification of Hepatic Fibrosis Based on Texture Parameters From Double Contrast-Enhanced Magnetic Resonance Images

PubMed Central

Bahl, Gautam; Cruite, Irene; Wolfson, Tanya; Gamst, Anthony C.; Collins, Julie M.; Chavez, Alyssa D.; Barakat, Fatma; Hassanein, Tarek; Sirlin, Claude B.

2016-01-01

Purpose To demonstrate a proof of concept that quantitative texture feature analysis of double contrast-enhanced magnetic resonance imaging (MRI) can classify fibrosis noninvasively, using histology as a reference standard. Materials and Methods A Health Insurance Portability and Accountability Act (HIPAA)-compliant Institutional Review Board (IRB)-approved retrospective study of 68 patients with diffuse liver disease was performed at a tertiary liver center. All patients underwent double contrast-enhanced MRI, with histopathology-based staging of fibrosis obtained within 12 months of imaging. The MaZda software program was used to compute 279 texture parameters for each image. A statistical regularization technique, generalized linear model (GLM)-path, was used to develop a model based on texture features for dichotomous classification of fibrosis category (F ≤2 vs. F ≥3) of the 68 patients, with histology as the reference standard. The model's performance was assessed and cross-validated. There was no additional validation performed on an independent cohort. Results Cross-validated sensitivity, specificity, and total accuracy of the texture feature model in classifying fibrosis were 91.9%, 83.9%, and 88.2%, respectively. Conclusion This study shows proof of concept that accurate, noninvasive classification of liver fibrosis is possible by applying quantitative texture analysis to double contrast-enhanced MRI. Further studies are needed in independent cohorts of subjects. PMID:22851409

Genetic variation in GPR133 is associated with height: genome wide association study in the self-contained population of Sorbs.

PubMed

Tönjes, Anke; Koriath, Moritz; Schleinitz, Dorit; Dietrich, Kerstin; Böttcher, Yvonne; Rayner, Nigel W; Almgren, Peter; Enigk, Beate; Richter, Olaf; Rohm, Silvio; Fischer-Rosinsky, Antje; Pfeiffer, Andreas; Hoffmann, Katrin; Krohn, Knut; Aust, Gabriela; Spranger, Joachim; Groop, Leif; Blüher, Matthias; Kovacs, Peter; Stumvoll, Michael

2009-12-01

Recently, associations of several common genetic variants with height have been reported in different populations. We attempted to identify further variants associated with adult height in a self-contained population (the Sorbs in Eastern Germany) as discovery set. We performed a genome wide association study (GWAS) (approximately 390,000 genetic polymorphisms, Affymetrix gene arrays) on adult height in 929 Sorbian individuals. Subsequently, the best SNPs (P < 0.001) were taken forward to a meta-analysis together with two independent cohorts [Diabetes Genetics Initiative, British 1958 Birth Cohort, (58BC, publicly available)]. Furthermore, we genotyped our best signal for replication in two additional German cohorts (Leipzig, n = 1044 and Berlin, n = 1728). In the primary Sorbian GWAS, we identified 5 loci with a P-value < 10(-5) and 455 SNPs with P-value < 0.001. In the meta-analysis on those 455 SNPs, only two variants in GPR133 (rs1569019 and rs1976930; in LD with each other) retained a P-value at or below 10(-6) and were associated with height in the three cohorts individually. Upon replication, the SNP rs1569019 showed significant effects on height in the Leipzig cohort (P = 0.004, beta = 1.166) and in 577 men of the Berlin cohort (P = 0.049, beta = 1.127) though not in women. The combined analysis of all five cohorts (n = 6,687) resulted in a P-value of 4.7 x 10(-8) (beta = 0.949). In conclusion, our GWAS suggests novel loci influencing height. In view of the robust replication in five different cohorts, we propose GPR133 to be a novel gene associated with adult height.

Incidence of seizures following initial ischemic stroke in a community-based cohort: The Framingham Heart Study.

PubMed

Stefanidou, Maria; Das, Rohit R; Beiser, Alexa S; Sundar, Banu; Kelly-Hayes, Margaret; Kase, Carlos S; Devinsky, Orrin; Seshadri, Sudha; Friedman, Daniel

2017-04-01

We examined the incidence of seizures following ischemic stroke in a community-based sample. All subjects with incident ischemic strokes in the Framingham Original and Offspring cohorts between 1982 and 2003 were identified and followed for up to 20 years to determine incidence of seizures. Seizure-type was based on the 2010 International League Against Epilepsy (ILAE) classification. Disability was stratified into mild/none, moderate and severe, based on post-stroke neurological deficit documentation according to the Framingham Heart Study (FHS) protocol and functional status was determined using the Barthel Index. An initial ischemic stroke occurred in 469 subjects in the cohort and seizures occurred in 25 (5.3%) of these subjects. Seizure incidence was similar in both large artery atherosclerosis (LAA) (6.8%) and cardio-embolic (CE) (6.2%) strokes. No seizures occurred following lacunar strokes. The predominant seizure type was focal seizure with or without evolution to bilateral convulsive seizure. One third of participants had seizures within the first 24h from stroke onset and half of all seizures occurred within the first 30days. On multivariate analysis, moderate and severe disability following stroke was associated with increased risk of incident seizure. Seizures occurred in approximately 5% of subjects after an ischemic stroke. One third of these seizures occurred in the first 24h after stroke and none followed lacunar strokes. Focal seizures with or without evolution in bilateral convulsive seizures were the most common seizure type. Moderate and severe disability was predictive of incident seizures. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Trends in sports-related concussion diagnoses in the USA: a population-based analysis using a private-payor database.

PubMed

Amoo-Achampong, Kelms; Rosas, Samuel; Schmoke, Nicholas; Accilien, Yves-Dany; Nwachukwu, Benedict U; McCormick, Frank

2017-09-01

To describe recent epidemiological trends in concussion diagnosis within the United States (US) population. We conducted a retrospective review of PearlDiver, a private-payor insurance database. Our search included International Classification of Disease, Ninth Revision codes for sports-related concussions spanning 2010 through 2014. Overall study population included patients aged 5 to 39 with subgroup analysis performed on Cohort A (Youth), children and adolescents aged 5 to 19, and Cohort B (Adults), adults aged 20 to 39. Incidence was defined as the number of individuals diagnosed normalized to the number of patients in the database for each demographic. Our search returned 1,599 patients diagnosed during the study period. The average (±SD) annual rate was 4.14 ± 1.42 per 100,000 patients for the overall population. Youth patients were diagnosed at a mean annual rate of 3.78 ± 1.30 versus 0.36 ± 0.16 per 100,000 in Adults. Concussion normalized incidence significantly increased from 2.47 to 3.87 per 100,000 patients (57%) in the Youth cohort (p = 0.048). In Adults, rate grew from 0.34 to 0.44 per 100,000 patients (29%) but was not statistically significant (p = 0.077). Four-year compound annual growth rates for Youth and Adults were 26.3% and 20.4%, respectively. Youth patients comprised 1,422/1,599 (90.18%) of all concussion diagnoses and were predominantly male (75%). Adults also constituted 138/1,599 (8.63%) of the sample and were also largely male (80%). Midwestern states had highest diagnostic rates (Cohort A:19 per 100,000 and Cohort B:1.8 per 100,000). Both cohorts had the most total diagnoses made in the fourth quarter followed by the second quarter. Sports-related concussion diagnostic rates have grown significantly in the youth population. Quarterly, regional and gender distributions appear consistent with participation in concussion-prone sports. Utilization of individualized and multifaceted approaches are recommended to advance diagnosis, assessment and management of concussions in the U.S.

The impact of rotavirus vaccination on discounted net tax revenue in Egypt: a government perspective analysis.

PubMed

Connolly, Mark P; Topachevskyi, Oleksandr; Standaert, Baudouin; Ortega, Omayra; Postma, Maarten

2012-08-01

We evaluated national rotavirus (RV) immunization programme costs to estimate how resulting changes in morbidity and mortality will influence government fiscal accounts over time. The assumption was that increased childhood survival in vaccinated cohorts leads to increased numbers of children consuming government resource, and an increased number of future tax payers. Our objective was to evaluate the difference in lifetime discounted net tax revenue generated by RV vaccinated and unvaccinated cohorts from the Egyptian government perspective. The model framework adopts the Egyptian government perspective for RV immunization costs (year 2009 values) and all government transfers (e.g. education costs, health costs, pensions). To reflect the government tax revenue, we applied a fixed income tax burden to earnings over the lifetime of vaccinated and unvaccinated cohorts. At each year of the model, we derive net taxes (gross taxes less transfers) discounted to the immunization year to reflect the present value of RV vaccination investment costs. Projected incremental net present values of the vaccinated cohort versus the unvaccinated cohort are $US6.1 million, $US58.1 million and $US55.7 million at 25-, 50- and 72-year time horizons, respectively. The internal rate of return for the government based on RV vaccination at years 25, 50 and 72 was 10.8%, 15.1% and 14.9, respectively. Within the first 5 years of vaccination, 76% of vaccine acquisition costs were offset due to direct and indirect cost savings attributed to a reduction in RV-related disease burden. Investments in RV vaccination in a single year are entirely offset when the vaccinated cohort of newborns reach 22 years of age. The government perspective is useful for evaluating investments in RV vaccination because of ongoing government transfers and tax receipts attributed to changes in RV-attributed morbidity and mortality. The analysis described here illustrates that investing in RV offers tangible long-term fiscal benefits for government over many generations that would not ordinarily be captured in economic evaluations typically applied to healthcare interventions.

Period Effects, Cohort Effects, and the Narrowing Gender Wage Gap

PubMed Central

Campbell, Colin; Pearlman, Jessica

2015-01-01

Despite the abundance of sociological research on the gender wage gap, questions remain. In particular, the role of cohorts is under investigated. Using data from the Current Population Survey, we use Age-Period-Cohort analysis to uniquely estimate age, period, and cohort effects on the gender wage gap. The narrowing of the gender wage gap that occurred between 1975 and 2009 is largely due to cohort effects. Since the mid-1990s, the gender wage gap has continued to close absent of period effects. While gains in female wages contributed to declines in the gender wage gap for cohorts born before 1950, for later cohorts the narrowing of the gender wage gap is primarily a result of declines in male wages. PMID:24090861

Association between Exposure of Young Children to Procedures Requiring General Anesthesia and Learning and Behavioral Outcomes in a Population-based Birth Cohort.

PubMed

Hu, Danqing; Flick, Randall P; Zaccariello, Michael J; Colligan, Robert C; Katusic, Slavica K; Schroeder, Darrell R; Hanson, Andrew C; Buenvenida, Shonie L; Gleich, Stephen J; Wilder, Robert T; Sprung, Juraj; Warner, David O

2017-08-01

Exposure of young animals to general anesthesia causes neurodegeneration and lasting behavioral abnormalities; whether these findings translate to children remains unclear. This study used a population-based birth cohort to test the hypothesis that multiple, but not single, exposures to procedures requiring general anesthesia before age 3 yr are associated with adverse neurodevelopmental outcomes. A retrospective study cohort was assembled from children born in Olmsted County, Minnesota, from 1996 to 2000 (inclusive). Propensity matching selected children exposed and not exposed to general anesthesia before age 3 yr. Outcomes ascertained via medical and school records included learning disabilities, attention-deficit/hyperactivity disorder, and group-administered ability and achievement tests. Analysis methods included proportional hazard regression models and mixed linear models. For the 116 multiply exposed, 457 singly exposed, and 463 unexposed children analyzed, multiple, but not single, exposures were associated with an increased frequency of both learning disabilities and attention-deficit/hyperactivity disorder (hazard ratio for learning disabilities = 2.17 [95% CI, 1.32 to 3.59], unexposed as reference). Multiple exposures were associated with decreases in both cognitive ability and academic achievement. Single exposures were associated with modest decreases in reading and language achievement but not cognitive ability. These findings in children anesthetized with modern techniques largely confirm those found in an older birth cohort and provide additional evidence that children with multiple exposures are more likely to develop adverse outcomes related to learning and attention. Although a robust association was observed, these data do not determine whether anesthesia per se is causal.

Genome-wide association study identifies SNPs in the MHC class II loci that are associated with self-reported history of whooping cough.

PubMed

McMahon, George; Ring, Susan M; Davey-Smith, George; Timpson, Nicholas J

2015-10-15

Whooping cough is currently seeing resurgence in countries despite high vaccine coverage. There is considerable variation in subject-specific response to infection and vaccine efficacy, but little is known about the role of human genetics. We carried out a case-control genome-wide association study of adult or parent-reported history of whooping cough in two cohorts from the UK: the ALSPAC cohort and the 1958 British Birth Cohort (815/758 cases and 6341/4308 controls, respectively). We also imputed HLA alleles using dense SNP data in the MHC region and carried out gene-based and gene-set tests of association and estimated the amount of additive genetic variation explained by common SNPs. We observed a novel association at SNPs in the MHC class II region in both cohorts [lead SNP rs9271768 after meta-analysis, odds ratio [95% confidence intervals (CIs)] 1.47 (1.35, 1.6), P-value 1.21E - 18]. Multiple strong associations were also observed at alleles at the HLA class II loci. The majority of these associations were explained by the lead SNP rs9271768. Gene-based and gene-set tests and estimates of explainable common genetic variation could not establish the presence of additional associations in our sample. Genetic variation at the MHC class II region plays a role in susceptibility to whooping cough. These findings provide additional perspective on mechanisms of whooping cough infection and vaccine efficacy. © The Author 2015. Published by Oxford University Press.

Hyperthyroidism and female urinary incontinence: a population-based cohort study.

PubMed

Chung, Shiu-Dong; Chen, Yi-Kuang; Chen, Yi-Hua; Lin, Herng-Ching

2011-11-01

The imbalanced autonomic nervous system present in hyperthyroidism may cause lower urinary tract symptoms. Urinary incontinence (UI) is the most bothersome lower urinary tract symptom; however, in the literature, reports regarding urinary dysfunction and/or incontinence among hyperthyroid patients are scarce. This population-based cohort study aimed to examine the relationship between hyperthyroidism in women and the risk of developing UI in Taiwan. This study used data from the Longitudinal Health Insurance Database. For this study, 10,817 female patients diagnosed with hyperthyroidism from 2001 to 2005 were recruited together with a comparison cohort of 54,085 matched enrollees who did not have a history of hyperthyroidism. All patients were tracked for a 3-year period from their index date to identify those who had a subsequent UI. The stratified Cox proportional hazards models were used to compute the risk of UI between study and comparison cohorts. During the follow-up period, of 64,169 patients, 173 (1·60%) from the hyperthyroidism group and 560 (1·04%) from the comparison group, had a diagnosis of UI. The regression analysis showed that, after adjusting for monthly income, geographic region, urbanization level of the community in which the patient resided, obesity and hysterectomy, patients with hyperthyroidism were more likely to have UI during the 3-year follow-up period than the comparison patients (hazard ratio = 1·54; 95% CI = 1·30-1·83; P < 0·001). Our results suggest an increased risk of UI in patients with hyperthyroidism at the 3-year follow-up. © 2011 Blackwell Publishing Ltd.

Integrated Database And Knowledge Base For Genomic Prospective Cohort Study In Tohoku Medical Megabank Toward Personalized Prevention And Medicine.

PubMed

Ogishima, Soichi; Takai, Takako; Shimokawa, Kazuro; Nagaie, Satoshi; Tanaka, Hiroshi; Nakaya, Jun

2015-01-01

The Tohoku Medical Megabank project is a national project to revitalization of the disaster area in the Tohoku region by the Great East Japan Earthquake, and have conducted large-scale prospective genome-cohort study. Along with prospective genome-cohort study, we have developed integrated database and knowledge base which will be key database for realizing personalized prevention and medicine.

Sex Differences in Faculty Salaries: A Cohort Analysis.

ERIC Educational Resources Information Center

Perna, Laura Walter

This study examined sex differences in faculty salaries, exploring how lower salaries for women varied across different rank/experience cohorts. Data came from the 1993 National Study of Postsecondary Faculty. Six cohorts were defined: assistant professors with 1-2 years experience, 3-6 years experience, 7-12 years experience, or 13-20 years…

Cohort Analysis of Variations in Political Knowledge.

ERIC Educational Resources Information Center

Caudill, Ed

A cohort analysis of data gathered in three national election surveys (1956, 1968, 1980) was used to study the effect of media use on political knowledge, which was divided into knowledge of issues, personalities, and political parties. Knowledge levels were calculated by creating indices from open-ended questions about why a person liked or…

IT Educational Experience and Workforce Development for Information Systems and Technology Students

ERIC Educational Resources Information Center

Legier, John T., Jr.; Soares, Andrey

2014-01-01

This study involves an analysis of a cohort of student's during their pursuit of a Bachelor of Science degree in Information Systems Technologies (IST) at a Midwestern university. Demographics and analysis of this cohort include basic demographic information, student home-life and personal responsibilities, employment and work experience, and…