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.

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.

Congenital Microphthalmia, Anophthalmia and Coloboma among Live Births in Denmark.

PubMed

Roos, Laura; Jensen, Hanne; Grønskov, Karen; Holst, René; Tümer, Zeynep

2016-10-01

This study aims to quantify the occurrence of the congenital eye malformations anophthalmia (AO), microphthalmia (MO) and coloboma among liveborn infants in Denmark, and to estimate the rate of chromosomal abnormalities in this group of patients. A cohort of patients born in 1995-2012 with diagnoses of MO/AO or coloboma was identified from the Danish National Patient Registry (DNPR), and their ocular and extra-ocular diagnoses were reviewed. In order to assess the occurrence of chromosomal abnormalities in the cohort, the data were cross-referenced with the Danish Cytogenetic Central Registry (DCCR). We identified 415 patients with MO/AO/coloboma in the DNPR. The total number of live births from 1995-2012 was 1,174,299, and the average birth prevalence of MO/AO/coloboma was 3.6/10,000 live births and of MO/AO was 1.2/10,000 live births. Extra-ocular abnormalities were observed in 32.1% of MO/AO cases and 21.7% of coloboma cases. Chromosome analysis was performed in 36.1% of the cohort, and 14.7% of cases had an abnormal karyotype. In 8.7% of the cohort, a chromosome microarray analysis was performed, and in 44.4% of cases, a possibly pathogenic copy number variation was observed. The birth prevalence of MO/AO/coloboma in Denmark has been steady at 3.6/10,000 live births during the last 17 years. The rate of syndromic cases was lower compared to other studies. A relatively high rate of pathogenic chromosomal aberrations was observed, suggesting an important role for cytogenetic analysis in this group of patients.

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.

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.

Multinational assessment of accuracy of equations for predicting risk of kidney failure: a meta-analysis

PubMed Central

Tangri, Navdeep; Grams, Morgan E.; Levey, Andrew S.; Coresh, Josef; Appel, Lawrence; Astor, Brad C.; Chodick, Gabriel; Collins, Allan J.; Djurdjev, Ognjenka; Elley, C. Raina; Evans, Marie; Garg, Amit X.; Hallan, Stein I.; Inker, Lesley; Ito, Sadayoshi; Jee, Sun Ha; Kovesdy, Csaba P.; Kronenberg, Florian; Lambers Heerspink, Hiddo J.; Marks, Angharad; Nadkarni, Girish N.; Navaneethan, Sankar D.; Nelson, Robert G.; Titze, Stephanie; Sarnak, Mark J.; Stengel, Benedicte; Woodward, Mark; Iseki, Kunitoshi

2016-01-01

Importance Identifying patients at risk of chronic kidney disease (CKD) progression may facilitate more optimal nephrology care. Kidney failure risk equations (KFREs) were previously developed and validated in two Canadian cohorts. Validation in other regions and in CKD populations not under the care of a nephrologist is needed. Objective To evaluate the accuracy of the KFREs across different geographic regions and patient populations through individual-participant data meta-analysis. Data Sources Thirty-one cohorts, including 721,357 participants with CKD Stages 3–5 in over 30 countries spanning 4 continents, were studied. These cohorts collected data from 1982 through 2014. Study Selection Cohorts participating in the CKD Prognosis Consortium with data on end-stage renal disease. Data Extraction and Synthesis Data were obtained and statistical analyses were performed between July 2012 and June 2015. Using the risk factors from the original KFREs, cohort-specific hazard ratios were estimated, and combined in meta-analysis to form new “pooled” KFREs. Original and pooled equation performance was compared, and the need for regional calibration factors was assessed. Main Outcome and Measure Kidney failure (treatment by dialysis or kidney transplantation). Results During a median follow-up of 4 years, 23,829 cases of kidney failure were observed. The original KFREs achieved excellent discrimination (ability to differentiate those who developed kidney failure from those who did not) across all cohorts (overall C statistic, 0.90 (95% CI 0.89–0.92) at 2 years and 0.88 (95% CI 0.86–0.90) at 5 years); discrimination in subgroups by age, race, and diabetes status was similar. There was no improvement with the pooled equations. Calibration (the difference between observed and predicted risk) was adequate in North American cohorts, but the original KFREs overestimated risk in some non-North American cohorts. Addition of a calibration factor that lowered the baseline risk by 32.9% at 2 years and 16.5% at 5 years improved the calibration in 12/15 and 10/13 non-North American cohorts at 2 and 5 years, respectively (p=0.04 and p=0.02). Conclusions and Relevance KFREs developed in a Canadian population showed high discrimination and adequate calibration when validated in 31 multinational cohorts. However, in some regions the addition of a calibration factor may be necessary. PMID:26757465

New insights into the effect of haemodiafiltration on mortality: the Romanian experience.

PubMed

Siriopol, Dimitrie; Canaud, Bernard; Stuard, Stefano; Mircescu, Gabriel; Nistor, Ionut; Covic, Adrian

2015-02-01

Haemodiafiltration (HDF), by successfully removing the larger solutes and protein-bound compounds, may offer a feasible approach to improve dialysis outcomes. Recently, three large, randomized, controlled trials have tested this hypothesis, but only one showed an improved survival associated with HDF treatment, when compared with haemodialysis (HD). This is a retrospective analysis of the entire Romanian dialysed population from the European Clinical Database (EUCLID) Fresenius Medical Care Database. We conducted two types of analysis. First, we used an intention-to-treat approach including all patients who were in dialysis (either HDF or HD) at 1 March 2010--'prevalent cohort analysis'. We then considered only the incident patients who started dialysis (either HDF or HD) after 1 March 2010--'incident cohort analysis'. In both analyses, patients were followed until 31 April 2013. In the prevalent cohort, we included 1546 patients who were already performing dialysis at the first time point-1322 on HD and 224 on HDF. When compared with HD, HDF treatment was associated with reduced mortality in both univariate and multivariate survival analysis (HR = 0.67, 95% CI 0.46-0.96 and HR = 0.58, 95% CI 0.36-0.93, respectively). In the incident cohort, 2447 patients started dialysis (2181 HD and 266 HDF) during the observation period. Patients in the HDF group maintained a reduced risk for all-cause mortality (HR = 0.20, 95% CI 0.11-0.38 for the univariate and HR = 0.24, 95% CI 0.13-0.46 for the fully adjusted model). This study suggests that HDF treatment could reduce all-cause mortality in incident and prevalent patients even after correction for different confounders. Interestingly, an additional survival benefit could be observed in incident patients. However, as with any observational study, there could have been other unmeasured confounders that could have influenced our final results. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Night Shift Work and Risk of Depression: Meta-analysis of Observational Studies.

PubMed

Lee, Aeyoung; Myung, Seung Kwon; Cho, Jung Jin; Jung, Yu Jin; Yoon, Jong Lull; Kim, Mee Young

2017-07-01

This study aimed to assess whether night shift work is associated with the risk of depression by using a meta-analysis of observational studies. We searched PubMed and EMBASE in August, 2016 to locate eligible studies and investigated the association between night shift work and the risk of depression, reporting outcome measures with adjusted odds ratios (ORs) or relative risks (RRs) and 95% confidence intervals (CIs). In the meta-analysis of a total of 11 observational studies with 9 cross-sectional study, 1 longitudinal study, and 1 cohort study, night shift work was significantly associated with an increased risk of depression (OR/RR, 1.43; 95% CI, 1.24-1.64; I² = 78.0%). Also, subgroup meta-analyses by gender, night shift work duration, type of occupation, continent, and type of publication showed that night shift work was consistently associated with the increased risk of depression. The current meta-analysis suggests that night shift work is associated with the increased risk of depression. However, further large prospective cohort studies are needed to confirm this association. © 2017 The Korean Academy of Medical Sciences.

Night Shift Work and Risk of Depression: Meta-analysis of Observational Studies

PubMed Central

2017-01-01

This study aimed to assess whether night shift work is associated with the risk of depression by using a meta-analysis of observational studies. We searched PubMed and EMBASE in August, 2016 to locate eligible studies and investigated the association between night shift work and the risk of depression, reporting outcome measures with adjusted odds ratios (ORs) or relative risks (RRs) and 95% confidence intervals (CIs). In the meta-analysis of a total of 11 observational studies with 9 cross-sectional study, 1 longitudinal study, and 1 cohort study, night shift work was significantly associated with an increased risk of depression (OR/RR, 1.43; 95% CI, 1.24–1.64; I2 = 78.0%). Also, subgroup meta-analyses by gender, night shift work duration, type of occupation, continent, and type of publication showed that night shift work was consistently associated with the increased risk of depression. The current meta-analysis suggests that night shift work is associated with the increased risk of depression. However, further large prospective cohort studies are needed to confirm this association. PMID:28581264

Tea consumption may decrease the risk of osteoporosis: an updated meta-analysis of observational studies.

PubMed

Guo, Ming; Qu, Hua; Xu, Lin; Shi, Da-Zhuo

2017-06-01

Several epidemiological investigations have evaluated the correlation between tea consumption and risk of osteoporosis, but the results are inconsistent. Therefore, we conducted an updated meta-analysis of observational studies to assess this association. We searched for all relevant studies including cohort, cross-sectional, and case-control studies published from database inception to July 15, 2016, using MEDLINE EMBASE, and Cochrane Library. Polled odds ratios (ORs) were calculated using the random-effect model. Fourteen articles (16 studies) that examined 138523 patients were included in this meta-analysis. Seven studies concerning bone mineral density (BMD) showed an increase in BMD with tea consumption, including 4 cross-sectional studies (OR, 0.04, 95% confidence interval [CI], 0.01-0.08) and 3 cohort studies (OR, 0.01; 95% CI, 0.01-0.01). The remaining 9 studies concerning fracture, including 6 case-control studies and 3 cohort studies, showed no association between tea consumption and osteoporotic fracture (OR, 0.86; 95% CI, 0.74-1.01). This updated meta-analysis demonstrates that tea consumption could increase BMD, but the association with osteoporotic fracture requires further investigation. Together, the results highlight the need for future, high-quality-designed clinical trials on tea consumption and osteoporosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Validity of the estimates of oral cholera vaccine effectiveness derived from the test-negative design.

PubMed

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

2016-01-20

The test-negative design (TND) has emerged as a simple method for evaluating vaccine effectiveness (VE). Its utility for evaluating oral cholera vaccine (OCV) effectiveness is unknown. We examined this method's validity in assessing OCV effectiveness by comparing the results of TND analyses with those of conventional cohort analyses. Randomized controlled trials of OCV were conducted in Matlab (Bangladesh) and Kolkata (India), and an observational cohort design was used in Zanzibar (Tanzania). For all three studies, VE using the TND was estimated from the odds ratio (OR) relating vaccination status to fecal test status (Vibrio cholerae O1 positive or negative) among diarrheal patients enrolled during surveillance (VE= (1-OR)×100%). In cohort analyses of these studies, we employed the Cox proportional hazard model for estimating VE (=1-hazard ratio)×100%). OCV effectiveness estimates obtained using the TND (Matlab: 51%, 95% CI:37-62%; Kolkata: 67%, 95% CI:57-75%) were similar to the cohort analyses of these RCTs (Matlab: 52%, 95% CI:43-60% and Kolkata: 66%, 95% CI:55-74%). The TND VE estimate for the Zanzibar data was 94% (95% CI:84-98%) compared with 82% (95% CI:58-93%) in the cohort analysis. After adjusting for residual confounding in the cohort analysis of the Zanzibar study, using a bias indicator condition, we observed almost no difference in the two estimates. Our findings suggest that the TND is a valid approach for evaluating OCV effectiveness in routine vaccination programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantifying and Adjusting for Disease Misclassification Due to Loss to Follow-Up in Historical Cohort Mortality Studies.

PubMed

Scott, Laura L F; Maldonado, George

2015-10-15

The purpose of this analysis was to quantify and adjust for disease misclassification from loss to follow-up in a historical cohort mortality study of workers where exposure was categorized as a multi-level variable. Disease classification parameters were defined using 2008 mortality data for the New Zealand population and the proportions of known deaths observed for the cohort. The probability distributions for each classification parameter were constructed to account for potential differences in mortality due to exposure status, gender, and ethnicity. Probabilistic uncertainty analysis (bias analysis), which uses Monte Carlo techniques, was then used to sample each parameter distribution 50,000 times, calculating adjusted odds ratios (ORDM-LTF) that compared the mortality of workers with the highest cumulative exposure to those that were considered never-exposed. The geometric mean ORDM-LTF ranged between 1.65 (certainty interval (CI): 0.50-3.88) and 3.33 (CI: 1.21-10.48), and the geometric mean of the disease-misclassification error factor (εDM-LTF), which is the ratio of the observed odds ratio to the adjusted odds ratio, had a range of 0.91 (CI: 0.29-2.52) to 1.85 (CI: 0.78-6.07). Only when workers in the highest exposure category were more likely than those never-exposed to be misclassified as non-cases did the ORDM-LTF frequency distributions shift further away from the null. The application of uncertainty analysis to historical cohort mortality studies with multi-level exposures can provide valuable insight into the magnitude and direction of study error resulting from losses to follow-up.

Insomnia and the risk of depression: a meta-analysis of prospective cohort studies.

PubMed

Li, Liqing; Wu, Chunmei; Gan, Yong; Qu, Xianguo; Lu, Zuxun

2016-11-05

Observational studies suggest that insomnia might be associated with an increased risk of depression with inconsistent results. This study aimed at conducting a meta-analysis of prospective cohort studies to evaluate the association between insomnia and the risk of depression. Relevant cohort studies were comprehensively searched from the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases (up to October 2014) and from the reference lists of retrieved articles. A random-effects model was used to calculate the pooled risk estimates and 95 % confidence intervals (CIs). The I 2 statistic was used to assess the heterogeneity and potential sources of heterogeneity were assessed with meta-regression. The potential publication bias was explored by using funnel plots, Egger's test, and Duval and Tweedie trim-and-fill methods. Thirty-four cohort studies involving 172,077 participants were included in this meta-analysis with an average follow-up period of 60.4 months (ranging from 3.5 to 408). Statistical analysis suggested a positive relationship between insomnia and depression, the pooled RR was 2.27 (95 % CI: 1.89-2.71), and a high heterogeneity was observed (I 2  = 92.6 %, P < 0.001). Visual inspection of the funnel plot revealed some asymmetry. The Egger's test identified evidence of substantial publication bias (P <0.05), but correction for this bias using trim-and-fill method did not alter the combined risk estimates. This meta-analysis indicates that insomnia is significantly associated with an increased risk of depression, which has implications for the prevention of depression in non-depressed individuals with insomnia symptoms.

Hepatitis E Seroprevalence in Europe: A Meta-Analysis

PubMed Central

Hartl, Johannes; Otto, Benjamin; Madden, Richie Guy; Webb, Glynn; Woolson, Kathy Louise; Kriston, Levente; Vettorazzi, Eik; Lohse, Ansgar W.; Dalton, Harry Richard; Pischke, Sven

2016-01-01

There have been large numbers of studies on anti-HEV IgG seroprevalence in Europe, however, the results of these studies have produced high variability of seroprevalence rates, making interpretation increasingly problematic. Therefore, the aim of this study was to develop a clearer understanding of anti-HEV IgG seroprevalence in Europe and identify risk groups for HEV exposure by a meta-analysis of published studies. Methods: All European HEV-seroprevalence studies from 2003 to 2015 were reviewed. Data were stratified by assay, geographical location, and patient cohort (general population, patients with HIV, solid-organ transplant recipients, chronic liver disease patients, and individuals in contact with swine/wild animals). Data were pooled using a mixed-effects model. Results: Four hundred thirty-two studies were initially identified, of which 73 studies were included in the analysis. Seroprevalence estimates ranged from 0.6% to 52.5%, increased with age, but were unrelated to gender. General population seroprevalence varied depending on assays: Wantai (WT): 17%, Mikrogen (MG): 10%, MP-diagnostics (MP): 7%, DiaPro: 4%, Abbott 2%. The WT assay reported significantly higher seroprevalence rates across all cohorts (p < 0.001). Individuals in contact with swine/wild animals had significantly higher seroprevalence rates than the general population, irrespective of assay (p < 0.0001). There was no difference between any other cohorts. The highest seroprevalence was observed in France (WT: 32%, MP: 16%) the lowest in Italy (WT: 7.5%, MP 0.9%). Seroprevalence varied between and within countries. The observed heterogeneity was attributed to geographical region (23%), assay employed (23%) and study cohort (7%). Conclusion: Seroprevalcence rates primarily depend on the seroassy that is used, followed by the geographical region and study cohort. Seroprevalence is higher in individuals exposed to swine and/or wild animals, and increases with age. PMID:27509518

Hepatitis E Seroprevalence in Europe: A Meta-Analysis.

PubMed

Hartl, Johannes; Otto, Benjamin; Madden, Richie Guy; Webb, Glynn; Woolson, Kathy Louise; Kriston, Levente; Vettorazzi, Eik; Lohse, Ansgar W; Dalton, Harry Richard; Pischke, Sven

2016-08-06

There have been large numbers of studies on anti-HEV IgG seroprevalence in Europe, however, the results of these studies have produced high variability of seroprevalence rates, making interpretation increasingly problematic. Therefore, the aim of this study was to develop a clearer understanding of anti-HEV IgG seroprevalence in Europe and identify risk groups for HEV exposure by a meta-analysis of published studies. All European HEV-seroprevalence studies from 2003 to 2015 were reviewed. Data were stratified by assay, geographical location, and patient cohort (general population, patients with HIV, solid-organ transplant recipients, chronic liver disease patients, and individuals in contact with swine/wild animals). Data were pooled using a mixed-effects model. Four hundred thirty-two studies were initially identified, of which 73 studies were included in the analysis. Seroprevalence estimates ranged from 0.6% to 52.5%, increased with age, but were unrelated to gender. General population seroprevalence varied depending on assays: Wantai (WT): 17%, Mikrogen (MG): 10%, MP-diagnostics (MP): 7%, DiaPro: 4%, Abbott 2%. The WT assay reported significantly higher seroprevalence rates across all cohorts (p < 0.001). Individuals in contact with swine/wild animals had significantly higher seroprevalence rates than the general population, irrespective of assay (p < 0.0001). There was no difference between any other cohorts. The highest seroprevalence was observed in France (WT: 32%, MP: 16%) the lowest in Italy (WT: 7.5%, MP 0.9%). Seroprevalence varied between and within countries. The observed heterogeneity was attributed to geographical region (23%), assay employed (23%) and study cohort (7%). Seroprevalcence rates primarily depend on the seroassy that is used, followed by the geographical region and study cohort. Seroprevalence is higher in individuals exposed to swine and/or wild animals, and increases with age.

Liver transplant center performance profiling: 2005-2011 reports of the Scientific Registry for Transplant Recipients.

PubMed

Kettelhut, Valeriya V; Nayar, Preethy

2013-06-01

CONTEXT-Transplant center performance profiling provides important information for various concerned parties. Comparing a transplant center's performance against the performance of the best-in-class centers may help in understanding the performance thresholds for the underperforming centers. OBJECTIVES-(1) To identify and describe "Centers for Medicare and Medicaid Services (CMS)-red-flag" performers and the "best-in-class" performers and (2) to examine the relationships between a center's performance profile and outcomes such as 1-year observed mortality, 1-month observed mortality, 1-year risk-adjusted mortality, and volume. METHODS-The data for analysis was obtained from the published reports on the Scientific Registry for Transplant Recipients (SRTR) website for adult liver transplant programs compiled for the rolling 2 1/2-year cohorts of patients and included 7 cohorts of liver transplant recipients in the study from January through July 1, 2002, through December 31, 2010. We defined 4 performance profiles: CMS-red-flag, lower-than-expected, higher-than-expected, and best-in-class performers. RESULTS-The current SRTR methods classify approximately 7% of the adult liver centers as CMS-red-flag performers and 6% of the centers as best-in-class performers in every reported period. Neither of the low-volume centers (<30 liver transplants per 2 1/2-year cohort) was profiled as CMS-red-flag until the 2010 reporting period. The transplant center's profile was significantly associated with the 1-year and 1-month observed mortality rates in every reported cohort (P< .001). CONCLUSION-The CMS-red-flag profile can be characterized with the following: (1) the highest observed 1-year mortality, (2) the highest observed 1-month mortality, (3) a very large difference between the observed and adjusted mortality rates, and (4) the center volume greater than 30 liver transplants per 2 1/2-year cohort. The SRTR methods are not sensitive for performance profiling in the centers that perform fewer than 30 orthotopic liver transplants per 2 1/2-year cohort.

What are the causal effects of breastfeeding on IQ, obesity and blood pressure? Evidence from comparing high-income with middle-income cohorts.

PubMed

Brion, Marie-Jo A; Lawlor, Debbie A; Matijasevich, Alicia; Horta, Bernardo; Anselmi, Luciana; Araújo, Cora L; Menezes, Ana Maria B; Victora, Cesar G; Smith, George Davey

2011-06-01

A novel approach is explored for improving causal inference in observational studies by comparing cohorts from high-income with low- or middle-income countries (LMIC), where confounding structures differ. This is applied to assessing causal effects of breastfeeding on child blood pressure (BP), body mass index (BMI) and intelligence quotient (IQ). Standardized approaches for assessing the confounding structure of breastfeeding by socio-economic position were applied to the British Avon Longitudinal Study of Parents and Children (ALSPAC) (N ≃ 5000) and Brazilian Pelotas 1993 cohorts (N ≃ 1000). This was used to improve causal inference regarding associations of breastfeeding with child BP, BMI and IQ. Analyses were extended to include results from a meta-analysis of five LMICs (N ≃ 10 000) and compared with a randomized trial of breastfeeding promotion. Findings Although higher socio-economic position was strongly associated with breastfeeding in ALSPAC, there was little such patterning in Pelotas. In ALSPAC, breastfeeding was associated with lower BP, lower BMI and higher IQ, adjusted for confounders, but in the directions expected if due to socioeconomic patterning. In contrast, in Pelotas, breastfeeding was not strongly associated with BP or BMI but was associated with higher IQ. Differences in associations observed between ALSPAC and the LMIC meta-analysis were in line with those observed between ALSPAC and Pelotas, but with robust evidence of heterogeneity detected between ALSPAC and the LMIC meta-analysis associations. Trial data supported the conclusions inferred by the cross-cohort comparisons, which provided evidence for causal effects on IQ but not for BP or BMI. While reported associations of breastfeeding with child BP and BMI are likely to reflect residual confounding, breastfeeding may have causal effects on IQ. Comparing associations between populations with differing confounding structures can be used to improve causal inference in observational studies.

Prenatal selective serotonin reuptake inhibitor use and the risk of autism spectrum disorder in children: A systematic review and meta-analysis.

PubMed

Kaplan, Yusuf C; Keskin-Arslan, Elif; Acar, Selin; Sozmen, Kaan

2016-12-01

To determine whether an up-to-date systematic review and meta-analysis of observational studies would support the previously suggested associations regarding prenatal selective serotonin reuptake inhibitor (SSRI) use and the risk for autism spectrum disorders (ASD) in children. PubMed/MEDLINE, Cochrane Central Register of Controlled Trials and Reprotox databases were searched; observational studies with an exposed and unexposed group were included. The meta-analysis of case-control studies demonstrated a significantly increased risk of ASD in the children whose mothers were prenatally exposed to SSRIs during different exposure time windows (except third trimester). The qualitative review of the cohort studies suggested inconsistent findings. The significant association between preconception-only SSRI exposure and ASD in the children and negative/inconsistent findings among cohort studies weaken the significant associations detected in this meta-analysis. We suggest that confounding by indication still cannot be ruled out regarding prenatal SSRI exposure and ASD in children. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

External Validation of the Updated Partin Tables in a Cohort of French and Italian Men

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

Bhojani, Naeem; Department of Urology, University of Montreal, Montreal, PQ; Salomon, Laurent

2009-02-01

Purpose: To test the discrimination and calibration properties of the newly developed 2007 Partin Tables in two European cohorts with localized prostate cancer. Methods: Data on clinical and pathologic characteristics were obtained for 1,064 men treated with radical prostatectomy at the Creteil University Health Center in France (n = 839) and at the Milan University Vita-Salute in Italy (n = 225). Overall discrimination was assessed with receiver operating characteristic curve analysis, which quantified the accuracy of stage predictions for each center. Calibration plots graphically explored the relationship between predicted and observed rates of extracapsular extension (ECE), seminal vesicle invasion (SVI)more » and lymph node invasion (LNI). Results: The rates of ECE, SVI, and LNI were 28%, 14%, and 2% in the Creteil cohort vs. 11%, 5%, and 5% in the Milan cohort. In the Creteil cohort, the accuracy of ECE, SVI, and LNI prediction was 61%, 71%, and 82% vs. 66%, 92% and 75% for the Milan cohort. Important departures were recorded between Partin Tables' predicted and observed rates of ECE, SVI, and LNI within both cohorts. Conclusions: The 2007 Partin Tables demonstrated worse performance in European men than they originally did in North American men. This indicates that predictive models need to be externally validated before their implementation into clinical practice.« less

Use of acetaminophen and risk of endometrial cancer: evidence from observational studies.

PubMed

Ding, Yuan-Yuan; Yao, Peng; Verma, Surya; Han, Zhen-Kai; Hong, Tao; Zhu, Yong-Qiang; Li, Hong-Xi

2017-05-23

Previous meta-analyses suggested that aspirin was associated with reduced risk of endometrial cancer. However, there has been no study comprehensively summarize the evidence of acetaminophen use and risk of endometrial cancer from observational studies. We systematically searched electronic databases (PubMed , EMBASE, Web of Science, and Cochrane Library) for relevant cohort or case-control studies up to February 28, 2017. Two independent authors performed the eligibility evaluation and data extraction. All differences were resolved by discussion. A random-effects model was applied to estimate summary relative risks (RRs) with 95% CIs. All statistical tests were two-sided. Seven observational studies including four prospective cohort studies and three case-control studies with 3874 endometrial cancer cases were included for final analysis. Compared with never use acetaminophen, ever use this drug was not associated with risk of endometrial cancer (summarized RR = 1.02; 95% CI: 0.93-1.13, I2 = 0%). Similar null association was also observed when compared the highest category of frequency/duration with never use acetaminophen (summarized RR = 0.88; 95% CI: 0.70-1.11, I2 = 15.2%). Additionally, the finding was robust in the subgroup analyses stratified by study characteristics and adjustment for potential confounders and risk factors. There was no evidence of publication bias by a visual inspection of a funnel plot and formal statistical tests. In summary, the present meta-analysis reveals no association between acetaminophen use and risk of endometrial cancer. More large scale prospective cohort studies are warranted to confirm our findings and carry out the dose-response analysis of aforementioned association.

Observational and Genetic Associations of Resting Heart Rate With Aortic Valve Calcium.

PubMed

Whelton, Seamus P; Mauer, Andreas C; Pencina, Karol M; Massaro, Joseph M; D'Agostino, Ralph B; Fox, Caroline S; Hoffmann, Udo; Michos, Erin D; Peloso, Gina M; Dufresne, Line; Engert, James C; Kathiresan, Sekar; Budoff, Matthew; Post, Wendy S; Thanassoulis, George; O'Donnell, Christopher J

2018-05-15

It is unknown if lifelong exposure to increased hemodynamic stress from an elevated resting heart rate (HR) may contribute to aortic valve calcium (AVC). We performed multivariate regression analyses using data from 1,266 Framingham Heart Study (FHS) Offspring cohort participants and 6,764 Multi-Ethnic Study of Atherosclerosis (MESA) participants. We constructed a genetic risk score (GRS) for HR using summary-level data in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) AVC Consortium to investigate if there was evidence in favor of a causal relation. AVC was present in 39% of FHS Offspring cohort participants and in 13% of MESA cohort participants. In multivariate adjusted models, participants in the highest resting HR quartiles had significantly greater prevalence of AVC, with a prevalence ratio of 1.19 (95% confidence interval [CI] 0.99 to 1.44) for the FHS Offspring cohort and 1.32 (95% CI 1.12 to 1.63) for the MESA cohort, compared with those in the lowest quartile. There was a similar increase in the prevalence of AVC per standard deviation increase in resting HR in both FHS Offspring (prevalence ratio 1.08, 95% CI 1.01 to 1.15) and MESA (1.10, 95% CI 1.03 to 1.17). In contrast with these observational findings, a HR associated GRS was not significantly associated with AVC. Although our observational analysis indicates that a higher resting HR is associated with AVC, our genetic results do not support a causal relation. Unmeasured environmental and/or lifestyle factors associated with both increased resting HR and AVC that are not fully explained by covariates in our observational models may account for the association between resting HR and AVC. Copyright © 2018. Published by Elsevier Inc.

Weight change by baseline BMI from three-year observational data: findings from the Worldwide Schizophrenia Outpatient Health Outcomes Database.

PubMed

Bushe, Chris J; Slooff, Cees J; Haddad, Peter M; Karagianis, Jamie L

2013-04-01

The aim was to explore weight and body mass index (BMI) changes by baseline BMI in patients completing three years of monotherapy with various first- and second-generation antipsychotics in a large cohort in a post hoc analysis of three-year observational data. Data were analyzed by antipsychotic and three baseline BMI bands: underweight/normal weight (BMI <25 kg/m²), overweight (25-30 kg/m²) and obese (>30 kg/m²). Baseline BMI was associated with subsequent weight change irrespective of the antipsychotic given. Specifically, a smaller proportion of patients gained ≥7% baseline bodyweight, and a greater proportion of patients lost ≥7% baseline bodyweight with increasing baseline BMI. For olanzapine (the antipsychotic associated with highest mean weight gain in the total drug cohort), the percentage of patients gaining ≥7% baseline weight was 45% (95% CI: 43-48) in the underweight/normal weight BMI cohort and 20% (95% CI: 15-27) in the obese BMI cohort; 7% (95% CI: 6-8) of the underweight/normal cohort and 19% (95% CI: 13-27) of the obese cohort lost ≥7% baseline weight. BMI has an association with the likelihood of weight gain or loss and should be considered in analyses of antipsychotic weight change.

Association of choline and betaine levels with cancer incidence and survival: A meta-analysis.

PubMed

Youn, Jiyoung; Cho, Eunyoung; Lee, Jung Eun

2018-03-22

Evidences suggest possible link between betaine and choline, methyl group donors, and cancer progression. We examined the association between choline and betaine levels and cancer incidence and survival in a meta-analysis of observational studies. We identified observational studies examining the association between choline and/or betaine levels from diet or blood and cancer incidence and survival by searching the PubMed and Web of Science databases for studies published up to Jan, 2018. After applying the selection criteria, 28 observational studies (9 case-control, 1 cross-sectional, and 18 cohort studies) were included. Relative risks (RRs) and 95% confidence intervals (CIs) were extracted, and combined RRs were calculated using random-effects models. Choline levels were not associated with cancer incidence in a meta-analysis of cohort studies. Betaine levels reduced the risk of cancer incidence in a meta-analysis of cohort studies; combined relative risks (RRs) (95% CIs) comparing the top with the bottom categories were 0.93 (0.87-0.99). When we analyzed separately according to exposure assessment method, combined RRs (95% CIs) comparing the top with the bottom categories of betaine levels were 0.87 (95% CI: 0.78-0.95) for dietary betaine and 0.88 (95% CI: 0.77-0.99) for blood levels of betaine. There were no significant associations with cancer survivorship of choline or betaine levels. We concluded that high betaine levels were associated with lower risk of the cancer incidence, especially for colorectal cancer. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Statins and secondary prevention of venous thromboembolism: pooled analysis of published observational cohort studies.

PubMed

Kunutsor, Setor K; Seidu, Samuel; Khunti, Kamlesh

2017-05-21

There have been suggestions that statins may have a potential role in secondary prevention of venous thromboembolism (VTE) [which includes deep vein thrombosis (DVT) and pulmonary embolism (PE)], but the evidence is inconsistent. We aimed to evaluate the association between statin use and risk of recurrent VTE. We conducted a systematic review and meta-analysis of observational cohort studies. All relevant studies which reported associations between statin use and recurrent VTE outcomes were identified from MEDLINE, EMBASE, Web of Science, and manual search of bibliographies from inception to January 2017. Study specific relative risks (RRs) with 95% confidence intervals were aggregated using random effects models. Eight eligible studies comprising of 103 576 participants and 13 168 recurrent VTE outcomes were included in the pooled analysis. In pooled analysis of 7 studies, the RR for recurrent VTE was 0.73 (0.68-0.79) when comparing statin use with no use. There was no evidence of heterogeneity between contributing studies (I2=0%, 0-71%; P = 0.93). The RRs for recurrent PE (three studies) and DVT (two studies) comparing statin use with no statin use were 0.75 (95% CI: 0.58-0.96) and 0.66 (95% CI: 0.60-0.71) respectively. Available evidence from observational cohort studies suggests a beneficial effect of statin use on VTE recurrence. Well-designed intervention studies are needed to corroborate these findings. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Multinational Assessment of Accuracy of Equations for Predicting Risk of Kidney Failure: A Meta-analysis.

PubMed

Tangri, Navdeep; Grams, Morgan E; Levey, Andrew S; Coresh, Josef; Appel, Lawrence J; Astor, Brad C; Chodick, Gabriel; Collins, Allan J; Djurdjev, Ognjenka; Elley, C Raina; Evans, Marie; Garg, Amit X; Hallan, Stein I; Inker, Lesley A; Ito, Sadayoshi; Jee, Sun Ha; Kovesdy, Csaba P; Kronenberg, Florian; Heerspink, Hiddo J Lambers; Marks, Angharad; Nadkarni, Girish N; Navaneethan, Sankar D; Nelson, Robert G; Titze, Stephanie; Sarnak, Mark J; Stengel, Benedicte; Woodward, Mark; Iseki, Kunitoshi

2016-01-12

Identifying patients at risk of chronic kidney disease (CKD) progression may facilitate more optimal nephrology care. Kidney failure risk equations, including such factors as age, sex, estimated glomerular filtration rate, and calcium and phosphate concentrations, were previously developed and validated in 2 Canadian cohorts. Validation in other regions and in CKD populations not under the care of a nephrologist is needed. To evaluate the accuracy of the risk equations across different geographic regions and patient populations through individual participant data meta-analysis. Thirty-one cohorts, including 721,357 participants with CKD stages 3 to 5 in more than 30 countries spanning 4 continents, were studied. These cohorts collected data from 1982 through 2014. Cohorts participating in the CKD Prognosis Consortium with data on end-stage renal disease. Data were obtained and statistical analyses were performed between July 2012 and June 2015. Using the risk factors from the original risk equations, cohort-specific hazard ratios were estimated and combined using random-effects meta-analysis to form new pooled kidney failure risk equations. Original and pooled kidney failure risk equation performance was compared, and the need for regional calibration factors was assessed. Kidney failure (treatment by dialysis or kidney transplant). During a median follow-up of 4 years of 721,357 participants with CKD, 23,829 cases kidney failure were observed. The original risk equations achieved excellent discrimination (ability to differentiate those who developed kidney failure from those who did not) across all cohorts (overall C statistic, 0.90; 95% CI, 0.89-0.92 at 2 years; C statistic at 5 years, 0.88; 95% CI, 0.86-0.90); discrimination in subgroups by age, race, and diabetes status was similar. There was no improvement with the pooled equations. Calibration (the difference between observed and predicted risk) was adequate in North American cohorts, but the original risk equations overestimated risk in some non-North American cohorts. Addition of a calibration factor that lowered the baseline risk by 32.9% at 2 years and 16.5% at 5 years improved the calibration in 12 of 15 and 10 of 13 non-North American cohorts at 2 and 5 years, respectively (P = .04 and P = .02). Kidney failure risk equations developed in a Canadian population showed high discrimination and adequate calibration when validated in 31 multinational cohorts. However, in some regions the addition of a calibration factor may be necessary.

Dietary fat intake and ovarian cancer risk: a meta-analysis of epidemiological studies

PubMed Central

Qiu, Wenlong; Lu, Heng; Qi, Yana; Wang, Xiuwen

2016-01-01

Observational studies assessing the association of dietary fat and risk of ovarian cancer yield discrepant results. Pertinent prospective cohort studies were identified by a PubMed search from inception to December 2015. Sixteen independent case-control and nine cohort studies on dietary fat intake were included, with approximately 900,000 subjects in total. Relative risks (RRs) with 95% confidence intervals were pooled using a random effects model. Heterogeneity, sensitivity analysis and publication bias were assessed; subgroup analysis and analysis stratified by EOC histology were conducted. The reported studies showed a significant increase of ovarian cancer risk with high consumption of total-, saturated-, and trans-fats, while serous ovarian cancer was more susceptible to dietary fat consumption than other pathological subtypes. No evidence of positive association between dietary fat intake and ovarian cancer risk was provided by cohort studies. Menopausal status, hormone replacement therapy, body mass index (BMI), and pregnancy times, modified the objective associations. In conclusion, the meta-analysis findings indicate that high consumption of total, saturated and trans-fats increase ovarian cancer risk, and different histological subtypes have different susceptibility to dietary fat. PMID:27119509

Fruit and vegetable consumption and risk of depression: accumulative evidence from an updated systematic review and meta-analysis of epidemiological studies.

PubMed

Saghafian, Faezeh; Malmir, Hanieh; Saneei, Parvane; Milajerdi, Alireza; Larijani, Bagher; Esmaillzadeh, Ahmad

2018-05-01

Findings from observational studies investigating the association between fruit and vegetable consumption and risk of depression were inconsistent. We conducted a systematic review and meta-analysis to summarise available data on the association between fruit and vegetable intake and depression. A systematic literature search of relevant reports published in Medline/PubMed, ISI (Web of Science), SCOPUS and Google Scholar until Oct 2017 was conducted. Data from 27 publications (sixteen cross-sectional, nine cohort and two case-control studies) on fruit, vegetables and/or total fruit and vegetable consumption in relation to depression were included in the systematic review. A total of eighteen studies that reported relative risks (RR), hazard ratios or OR for the relationship were included in the meta-analysis. The pooled RR for depression in the highest v. the lowest category of fruit intake was 0·83 (95 % CI 0·71, 0·98) in cohort studies and 0·76 (95 % CI 0·63, 0·92) in cross-sectional studies. Consumption of vegetables was also associated with a 14 % lower risk of depression (overall RR=0·86; 95 % CI 0·75, 0·98) in cohort studies and a 25 % lower risk of depression (overall RR=0·75; 95 % CI 0·62, 0·91) in cross-sectional studies. Moreover, an inverse significant association was observed between intake of total fruit and vegetables and risk of depression (overall RR=0·80; 95 % CI 0·65, 0·98) in cross-sectional studies. In a non-linear dose-response association, we failed to find any significant association between fruit or vegetable intake and risk of depression (fruit (cross-sectional studies): P non-linearty=0·12; vegetables (cross-sectional studies): P non-linearty<0·001; (cohort studies) P non-linearty=0·97). Meta-regression of included observational studies revealed an inverse linear association between fruit or vegetable intake and risk of depression, such that every 100-g increased intake of fruit was associated with a 3 % reduced risk of depression in cohort studies (RR=0·97; 95 % CI 0·95, 0·99). With regard to vegetable consumption, every 100-g increase in intake was associated with a 3 % reduced risk of depression in cohort studies (RR=0·97; 95 % CI 0·95, 0·98) and 5 % reduced odds in cross-sectional studies (RR=0·95; 95 % CI 0·91, 0·98). This meta-analysis of observational studies provides further evidence that fruit and vegetable intake was protectively associated with depression. This finding supports the current recommendation of increasing fruit and vegetable intake to improve mental health.

Weight change and all-cause mortality in older adults: A meta-analysis

USDA-ARS?s Scientific Manuscript database

This meta-analysis of observational cohort studies examined the association between weight change (weight loss, weight gain, and weight fluctuation) and all-cause mortality among older adults. We used PubMed (MEDLINE), Web of Science, and Cochrane Library to identify prospective studies published in...

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

Increasing mumps incidence rates among children and adolescents in the Republic of Korea: age-period-cohort analysis.

PubMed

Choe, Young-June; Lee, Young Hwa; Cho, Sung-Il

2017-04-01

To characterize the temporal dynamics of mumps epidemiology according to the different vaccine strains used, sex-specific trends were decomposed in an age-period-cohort (APC) analysis for mumps cases reported in South Korea. National surveillance data were used to describe the epidemiology of mumps cases from 2001 to 2015. An APC model was used to break down the reported mumps cases into the effects of age, period, and birth cohort. From 2001 to 2015, the incidence started to increase from fewer than 10 cases to more than 100 cases per 100 000. The incidence rate was highest among males aged 15-17 years during 2013-2015, reaching 508.7 per 100 000 persons. There was an increased incidence during the late teenage years in the 1998-2000 cohort. An age shift towards the earlier teenage years was observed across the 2001-2003 and 2004-2006 cohorts. The risk of mumps increased according to the birth cohort; the net drift from 2001 to 2015 was 27.67 (95% confidence interval 27.5.47-29.90) for males and 27.25 (95% confidence interval 24.91-29.65) for females. The increase in mumps seen in Korea may have been affected by the birth cohort exposed to the Rubini strain; however other factors may have contributed to the increase in non-exposed cohorts. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

GFR at Initiation of Dialysis and Mortality in CKD: A Meta-analysis

PubMed Central

Susantitaphong, Paweena; Altamimi, Sarah; Ashkar, Motaz; Balk, Ethan M.; Stel, Vianda S.; Wright, Seth; Jaber, Bertrand L.

2012-01-01

Background The proportion of patients with advanced chronic kidney disease (CKD) initiating dialysis at higher glomerular filtration rate (GFR) has increased over the past decade. Recent data suggest that higher GFR may be associated with increased mortality. Study Design A meta-analysis of cohort studies and trials. Setting & Population Patients with advanced CKD. Selection Criteria for Studies We performed a systematic literature search in MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, American Society of Nephrology abstracts, and bibliographies of retrieved articles to identify studies reporting on GFR at dialysis initiation and mortality. Predictor estimated or calculated GFR at dialysis initiation. Outcome Pooled adjusted hazard ratio (HR) of continuous GFR for all-cause mortality. Results Sixteen cohort studies and one randomized controlled trial were identified (n=1,081,116). By meta-analysis, restricted to the 15 cohorts (n=1,079,917), higher GFR at dialysis initiation was associated with a higher pooled adjusted HR for all-cause mortality (1.04; 95% CI, 1.03–1.05; P<0.001). However, there was significant heterogeneity (I2=97%; P<0.001). The association persisted among the 9 cohorts that adjusted analytically for nutritional covariates (HR 1.03; 95% CI 1.02, 1.04; P<0.001; residual I2=97%). The highest mortality risk was observed in hemodialysis cohorts (HR 1.05; 95% CI 1.02, 1.08; P<0.001) whereas there was no association between GFR and mortality in peritoneal dialysis cohorts (HR 1.04; 95% CI 0.99, 1.08, P=0.11; residual I2=98%). Finally, higher GFR was associated with a lower mortality risk in cohorts that calculated GFR (HR 0.80; 95% CI 0.71, 0.91; P=0.003), contrasting with a higher mortality risk in cohorts that estimated GFR (HR 1.04; 95% CI 1.03, 1.05; P<0.001; residual I2=97%). Limitations Paucity of randomized controlled trials; different methods for determining GFR; and substantial heterogeneity. Conclusions Higher estimated rather than calculated GFR at dialysis initiation is associated with a higher mortality risk among patients with advanced CKD, independent of nutritional status. Although there was substantial heterogeneity of effect size estimates across studies, this observation requires further study. PMID:22465328

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

Healthcare resource use in advanced prostate cancer patients treated with docetaxel.

PubMed

Mehra, Maneesha; Wu, Ying; Dhawan, Ravinder

2012-01-01

Although the treatment of metastatic castrate-resistant prostate cancer (mCRPC) has improved with newer therapies, there is little understanding how these therapies have impacted resource use and associated expenditures; available estimates are dated. The current study examined contemporary healthcare utilization and associated costs for mCRPC patients and how these measures changed over time. This retrospective cohort analysis used medical and pharmaceutical insurance claims data from a large non-payer-owned integrated claims database of US commercial insurers. Amongst all patients with a prostate cancer diagnosis (n=256,464), those with ≥ 1 docetaxel claim (docetaxel cohort, n=3642) were identified as mCRPC patients. Within the docetaxel cohort, an additional 6-months follow-up cohort (n=2862) was identified, i.e., patients with at least 6 months of follow-up after the first docetaxel claim. Resource utilization and costs were identified for all-cause hospitalizations, emergency room (ER) visits, physician visits and ambulatory visits, and prostate cancer-related prescription treatments. Significant increases in the mean per-patient-per-month (PPPM) count for the docetaxel cohort were observed for all medical resources measured (hospitalizations and ER, physician, and ambulatory visits) in the post-docetaxel period compared with the pre-docetaxel period (p<0.0001); similar significant increases were observed for the 6-months follow-up cohort in the last 6 months (prior to lost to follow-up date) compared with the period preceding the last 6 months (p<0.0408 ambulatory visits, p<0.0001 all other resources). Total docetaxel cohort costs (mean [standard deviation]) rose from an average PPPM cost of US$2593 (3208) in the pre-docetaxel period to US$5847 (6990) in the post-docetaxel period (p<0.0001); each of the individual resources measured (hospitalization, all healthcare visits, and prescription costs) demonstrated significant increases (p<0.0001). Retrospective study design. This large database analysis showed a significant increase in use of healthcare resources and associated costs among mCRPC patients following first-line docetaxel treatment.

[Assessment of risk of death due to malignant neoplasms induced by occupational exposure in a rubber footwear plant].

PubMed

Szymczak, Wiesław; Sobala, Wojciech; Wilczyńska, Urszula; Szeszenia-Dabrowska, Neonila

2003-01-01

The main goal of the study was to analyze thoroughly the results of a cohort study. Such an analysis renders it possible to eliminate certain neoplasms as those not related to the observed exposure. The cohort study was carried out in a group of workers, covering 11,342 persons (5472 men and 5870 women), employed for at least one year during the years 1945-1985 in a rubber footwear plant. The cohort study was continued until the end of December 1997. Of all the sites of malignant neoplasms observed in the cohort, significant, exposure-related excess mortality was found to be due to malignant neoplasms of larynx and lung in men, and malignant neoplasms of gallbladder and lung in women. For these neoplasms, the values of observed risk among those exposed were significantly higher than among non-exposed. Moreover, in a certain interval of employment duration, an increase in risk rates with increasing duration of employment under exposure was observed, which suggests the presence of dose-response relationship. For all these sites, a relevant trend was shown by the RR values calculated in relation to the group of persons non-exposed but employed in the same plant. The internal reference group used to calculate RR values allowed to eliminate the effect of confounding variables, which is not always possible when the general population is used as the reference group.

Trends of stomach cancer mortality in Eastern Asia in 1950-2004: comparative study of Japan, Hong Kong and Singapore using age, period and cohort analysis.

PubMed

Tanaka, Masahiro; Ma, Enbo; Tanaka, Hideo; Ioka, Akiko; Nakahara, Toshitaka; Takahashi, Hideto

2012-02-15

To characterize the temporal trends of stomach cancer mortality in Eastern Asia and to better interpret the causes of the trends, we performed age, period and cohort analysis (APC analysis) on the mortality rates in Japan, Hong Kong and Singapore during 1950-2004, as well as the rates in the US as a control population. For the APC analysis, Holford's approach was used to avoid the identification problem. Age-standardized mortality rates (ASMR) decreased consistently in all four areas during the observation period in both males and females. Japan had the highest ASMR in both sexes, followed by Singapore, Hong Kong and the US, but the differences in ASMR among the four areas diminished with time. The results of APC analysis suggested that the decreasing mortality rates in Eastern Asia were caused by the combination of decreasing cohort effect since the end of the 1800s and decreasing period effect from the 1950s. The US showed similar results, but its decreases in the period and cohort effect preceded those of Eastern Asia. Possible causes for the decrease in the cohort effect include improvement in the socioeconomic conditions during childhood and a decrease in the prevalence of H. pylori infection, while possible causes for the decrease in the period effect include a decrease in dietary salt intake and improvements in cancer detection and treatment. These findings may help us to predict future changes in the mortality rates of stomach cancer. Copyright © 2011 UICC.

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.

Obesity and the risk of systemic lupus erythematosus among women in the Nurses' Health Studies.

PubMed

Tedeschi, Sara K; Barbhaiya, Medha; Malspeis, Susan; Lu, Bing; Sparks, Jeffrey A; Karlson, Elizabeth W; Willett, Walter; Costenbader, Karen H

2017-12-01

Obesity is increasingly prevalent and related to increased risk of several autoimmune diseases, likely via generation of inflammatory adipokines. Prior studies have not evaluated obesity in relation to systemic lupus erythematosus (SLE) risk. We prospectively evaluated whether obesity was associated with increased SLE risk among women in the U.S. Nurses' Health Study cohorts. We conducted a prospective cohort study among 238,130 women in the Nurses' Health Studies (NHS, 1976-2012; NHSII, 1989-2013). Incident SLE was confirmed by American College of Rheumatology 1997 criteria and validated through medical record review. Body mass index (BMI, kg/m 2 ) was calculated at baseline and on biennial questionnaires. Cox proportional hazards models estimated HRs (95% CIs) for SLE by cumulative average BMI category {18.5 to <25 [normal (reference)], 25 to <30 (overweight), ≥30 (obese)}, adjusting for potential time-varying confounders. Models were performed separately in each cohort; results were meta-analyzed. Sensitivity analyses used simple time-varying BMI, a 4-year lag between exposure and SLE risk window to address potential reverse causation, and evaluated BMI at age 18 and weight change since age 18. A secondary analysis started follow-up in both cohorts at similar calendar years when the prevalence of obesity in the U.S. increased most dramatically [1988 (NHS)/1989 (NHSII)]. We identified 153 NHS incident SLE cases and 115 incident NHSII cases during 5,602,653 person-years of follow-up. At baseline, 8.4% of women in NHS and 11.8% in NHSII were obese. Mean age at enrollment was 42.5 (SD 7.2) years in NHS and 34.4 (SD 4.7) years in NHSII. Cumulative average obesity was significantly associated with SLE risk in NHSII [HR = 1.85 (1.17-2.91)], but not in NHS [HR = 1.11 (0.65-1.87)] compared to normal BMI. In the meta-analysis of both cohorts, obesity was not significantly associated with increased risk of SLE [HR = 1.46 (0.88-2.40)]. Simple time-varying BMI and lagging the exposure window by 4 years produced similar findings to the primary analysis. In NHSII, a 4.54 kg gain between age 18 and enrollment slightly increased SLE risk [HR = 1.09 (1.02-1.18)]. In the secondary analysis starting follow-up of both cohorts at similar calendar years, the point estimate for obesity in NHS was higher than the primary analysis [HR = 1.67 (0.81-3.45)]. We observed an 85% significantly increased risk of SLE among obese compared to normal BMI women in the more recent NHSII cohort, but no association was observed in the earlier NHS cohort. Secular trends in obesity may account for the differences between the two birth cohorts. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Cigarette smoking and the risk of adult leukemia: results from the Three Mile Island cohort study.

PubMed

Xu, Xiaohui; Talbott, Evelyn O; Zborowski, Jeanne V; Rager, Judith R

2007-01-01

Smoking is an unconfirmed risk factor for the development of leukemia. The authors examined the potential link using data from the Three Mile Island cohort for the period 1979-1995. Eligible for analysis were 24,539 individuals aged 14 years or older who were followed up over 16 years from the Three Mile Island cohort. The authors identified all incident leukemia cases through the Pennsylvania Department of Health Cancer Registry. They used the Cox proportional hazards model to evaluate the relationships and observed 42 incident leukemia cases, including 15 acute myeloid leukemia (AML) cases, in the cohort. After controlling for other confounding factors, the authors found current smoking to be associated with an increased risk of adult AML (relative risk = 3.47; 95% confidence interval = 1.002-11.99). The authors also observed a marginally significant linear trend of risk of AML associated with the number of years smoked (p = .06). The results from this study suggested that cigarette smoking was associated with an increased risk of adult AML. Further investigation is required to confirm these findings.

Deaths and tumours among workers grinding stainless steel: a follow up.

PubMed Central

Jakobsson, K; Mikoczy, Z; Skerfving, S

1997-01-01

OBJECTIVE: To study cause specific mortality and cancer morbidity in workers exposed to the dust of grinding materials, grinding agents, and stainless steel, especially with regard to a possibly increased risk of respiratory, stomach, and colorectal cancer. METHODS: Retrospective cohort study, using reference cohorts of blue collar workers and population rates for comparison. The exposed cohort comprises workers with at least 12 months employment time at two plants, producing stainless steel sinks and saucepans (n = 727). Also, reference cohorts of other industrial workers (n = 3965) and fishermen (n = 8092) were analysed. The observation period began 15 years after the start of employment. Standardised mortality or incidence ratios (SMRs, SIRs; county reference rates) were calculated for cause-specific mortality between 1952 and 1993, and for cancer morbidity between 1958 and 1992. RESULTS: In the exposed cohort, overall mortality, cardiovascular mortality, and all malignant mortality and morbidity were slightly lower than expected. Also, the risk estimates for cancer in the upper and lower respiratory tracts and for stomach cancer were lower than expected. There was an increase in morbidity from colon cancer, which was explained by an excess of tumours in the sigmoid part only. Here, the risk estimates were higher in workers with long employment time (1-14 years: four observed cases, SIR 1.7, 95% confidence interval (95% CI) 0.4 to 4.5; > or = 15 years: three observed cases, SIR 4.3, 95% CI 0.9 to 13) and the increased risk was especially pronounced among those first employed before 1942. A slight nominal excess of rectal cancers (nine observed cases, SIR 1.4, 95% CI 0.6 to 2.6), and a significant excess of prostate cancer morbidity (36 observed cases, SIR 1.7, 95% CI 1.2 to 2.4) were found. These risk estimates did not, however, increase with employment time. CONCLUSIONS: The finding of an increased risk of cancer in the sigmoid part of the colon, which was not found in the reference cohorts, and with indication of a relation between duration of employment and response, is consistent with a causal relation. The limited size of the exposed cohort makes a detailed exposure-response analysis unstable, and the confidence limits are wide. Albeit slightly raised, the risk estimate for rectal cancer in the exposed cohort was not different from the estimate among the other industrial workers. PMID:9538356

Effects of etomidate on complications related to intubation and on mortality in septic shock patients treated with hydrocortisone: a propensity score analysis

PubMed Central

2012-01-01

Introduction Endotracheal intubation in the ICU is associated with a high incidence of complications. Etomidate use is debated in septic shock because it increases the risk of critical illness-related corticosteroid insufficiency, which may impact outcome. We hypothesized that hydrocortisone, administered in all septic shock cases in our ICU, may counteract some negative effects of etomidate. The aim of our study was to compare septic shock patients who received etomidate versus another induction drug both for short-term safety and for long-term outcomes. Methods A single-center observational study was carried out in septic shock patients, treated with hydrocortisone and intubated within the first 48 hours of septic shock. Co-primary end points were life-threatening complications incidence occurring within the first hour after intubation and mortality during the ICU stay. Statistical analyses included unmatched and matched cohorts using a propensity score analysis. P < 0.05 was considered significant. Results Sixty patients in the etomidate cohort and 42 patients in the non-etomidate cohort were included. Critical illness-related corticosteroid insufficiency was 79% in the etomidate cohort and 52% in the non-etomidate cohort (P = 0.01). After intubation, life-threatening complications occurred in 36% of the patients whatever the cohort. After adjustment with propensity score analysis, etomidate was a protective factor for death in the ICU both in unmatched (hazard ratio, 0.33 (0.15 to 0.75); P < 0.01)) and matched cohorts (hazard ratio, 0.33 (0.112 to 0.988); P = 0.04). Conclusion In septic shock patients treated with hydrocortisone, etomidate did not decrease life-threatening complications following intubation, but when associated with hydrocortisone it also did not impair outcome. PMID:23171852

Controlling firearms use in Australia: has the 1996 gun law reform produced the decrease in rates of suicide with this method?

PubMed

Klieve, Helen; Barnes, Michael; De Leo, Diego

2009-04-01

Observed reductions in firearm suicides in Australia have been linked to the 1997 national firearms agreement (NFA) introduced following the 1996 Port Arthur massacre. The NFA placed strong access restrictions on firearms. To assess the impact of legislative restrictions on the incidence of firearm suicide in Queensland and explore alternative or contributory factors behind observed declines. The Queensland suicide register (QSR) provided detailed information on all male suicides in Queensland (1990-2004), with additional data for Australia (1968-2004) accessed from other official sources. Trends in suicide rates pre/post NFA, and in method selection, were assessed using negative binomial regressions. Changing method selection patterns were examined using a cohort analysis of 5 years of age classes for Australian males. The observed reduction in firearms suicides was initiated prior to the 1997 introduction of the NFA in Queensland and Australia, with a clear decline observed in Australian figures from 1988. No significant difference was found in the rate pre/post the introduction of the NFA in Queensland; however, a significant difference was found for Australian data, the quality of which is noticeably less satisfactory. A marked age-difference in method choice was observed through a cohort analysis demonstrating both time and age influences. Within sequential birth cohorts, rates of firearms suicides decreased in younger males but increased in hanging suicides; this trend was far less marked in older males. The implemented restrictions may not be responsible for the observed reductions in firearms suicide. Data suggest that a change in social and cultural attitudes could have contributed to the shift in method preference.

Analysis of the North Carolina long-term care polypharmacy initiative: a multiple-cohort approach using propensity-score matching for both evaluation and targeting.

PubMed

Trygstad, Troy K; Christensen, Dale B; Wegner, Steve E; Sullivan, Rob; Garmise, Jennifer M

2009-09-01

The high cost and undesirable consequences of polypharmacy are well-recognized problems among elderly long-term care (LTC) residents. Despite the implementation of the 1987 Omnibus Budget Reconciliation Act, which requires pharmacist review of drug regimens in this setting, medical and drug costs for LTC residents have continued to increase. This study evaluates the North Carolina Long-Term Care Polypharmacy Initiative, a large-scale medication therapy management program (MTMP) that combined drug utilization review activities with drug regimen review techniques. This was a prospective records-based study that used a difference-in-difference model with both historical and nonintervention group controls. To ensure equivalence among subjects, propensity scoring was used to match study subjects from participating LTC facilities with comparison subjects from nonparticipating facilities. Residents with interventions were grouped for analysis by intervention type-retrospective only, prospective only, or dual type (residents with both prospective and retrospective interventions)-and by intervention stage-review, recommendation, and drug change-plus an all-inclusive "all types" grouping that aggregated groups by intervention type, for a total of 10 total cohorts. In the overall population of 5255 study subjects identified, a US $21.63 per member per month drug-cost savings was observed. Although only 1 of 10 cohorts had a change in the number of drug fills, substantial reductions in 2 of 5 types of drug alerts were observed in all 10 cohorts. A reduction in the relative risk for hospitalization (0.84 [95% CI, 0.71-1.00]) was observed in the cohort of residents receiving a retrospective review. This Initiative suggests that an MTMP can be quickly launched in a large number of LTC facility residents to produce monetary drug-cost savings and improved health outcomes. Additionally, the evaluation of this program illustrates the utility of using propensity scoring techniques to target future intervention groups in a cost-effective manner.

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.

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.

Risk of new onset autoimmune disease in 9- to 25-year-old women exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United Kingdom.

PubMed

Willame, Corinne; Rosillon, Dominique; Zima, Julia; Angelo, Maria-Genalin; Stuurman, Anke L; Vroling, Hilde; Boggon, Rachael; Bunge, Eveline M; Pladevall-Vila, Manel; Baril, Laurence

2016-11-01

To assess the risk of autoimmune disease (AD) in 9-25 year-old women within 1 year after the first AS04-HPV-16/18vaccine dose, a retrospective, observational database cohort study was conducted using CPRD GOLD. From CPRD GOLD 4 cohorts (65,000 subjects each) were retrieved: 1 exposed female cohort (received ≥1 AS04-HPV-16/18 vaccine dose between Sep2008-Aug2010) and 3 unexposed cohorts: historical female (Sep2005-Aug2007), concurrent male, and historical male. Co-primary endpoints were confirmed neuroinflammatory/ophthalmic AD and other AD, secondary endpoints were confirmed individual AD. Risk of new onset of AD was compared between cohorts (reference: historical cohort) using Poisson regression. The main analysis using confirmed cases showed no neuroinflammatory/ophthalmic AD cases in the female exposed cohort. Incidence rate ratio (IRR) (95% CI) of other AD was 1.41 (0.86 to 2.31) in female and 1.77 (0.94 to 3.35) in male cohorts when compared to the female and male historical cohort, respectively. Secondary endpoints were evaluated for diseases with >10 cases, which were Crohn's disease (IRR: 1.21 [0.37 to 3.95] for female and 4.22 [0.47 to 38.02] for male cohorts), autoimmune thyroiditis (IRR: 3.75 [1.25 to 11.31] for female and no confirmed cases for male cohorts) and type 1 diabetes (IRR: 0.30 [0.11 to 0.83] for female and 2.46 [1.08 to 5.60] for male cohorts). Analysis using confirmed and non-confirmed cases showed similar results, except for autoimmune thyroiditis in females, IRR: 1.45 (0.79 to 2.64). There was no evidence of an increased risk of AD in women aged 9 to 25 years after AS04-HPV-16/18 vaccination.

No association of SORL1 SNPs with Alzheimer's disease.

PubMed

Minster, Ryan L; DeKosky, Steven T; Kamboh, M Ilyas

2008-08-01

SORL1 is an element of the amyloid precursor protein processing pathway and is therefore a good candidate for affecting Alzheimer's disease (AD) risk. Indeed, there have been reports of associations between variation in SORL1 and AD risk. We examined six statistically significant single-nucleotide polymorphisms from the initial observation in a large Caucasian American case-controls cohort (1000 late-onset AD [LOAD] cases and 1000 older controls). Analysis of allele, genotype and haplotype frequencies revealed no association with LOAD risk in our cohort.

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis.

PubMed

Abbott, T E F; Ahmad, T; Phull, M K; Fowler, A J; Hewson, R; Biccard, B M; Chew, M S; Gillies, M; Pearse, R M

2018-01-01

The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32-0.77); P<0.01], but no difference in complication rates [OR 1.02 (0.88-1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62-0.92); P<0.01; I 2 =87%] and reduced complication rates [OR 0.73 (0.61-0.88); P<0.01; I 2 =89%). Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine. Copyright © 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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

Potential serum biomarkers from a metabolomics study of autism

PubMed Central

Wang, Han; Liang, Shuang; Wang, Maoqing; Gao, Jingquan; Sun, Caihong; Wang, Jia; Xia, Wei; Wu, Shiying; Sumner, Susan J.; Zhang, Fengyu; Sun, Changhao; Wu, Lijie

2016-01-01

Background Early detection and diagnosis are very important for autism. Current diagnosis of autism relies mainly on some observational questionnaires and interview tools that may involve a great variability. We performed a metabolomics analysis of serum to identify potential biomarkers for the early diagnosis and clinical evaluation of autism. Methods We analyzed a discovery cohort of patients with autism and participants without autism in the Chinese Han population using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS/MS) to detect metabolic changes in serum associated with autism. The potential metabolite candidates for biomarkers were individually validated in an additional independent cohort of cases and controls. We built a multiple logistic regression model to evaluate the validated biomarkers. Results We included 73 patients and 63 controls in the discovery cohort and 100 cases and 100 controls in the validation cohort. Metabolomic analysis of serum in the discovery stage identified 17 metabolites, 11 of which were validated in an independent cohort. A multiple logistic regression model built on the 11 validated metabolites fit well in both cohorts. The model consistently showed that autism was associated with 2 particular metabolites: sphingosine 1-phosphate and docosahexaenoic acid. Limitations While autism is diagnosed predominantly in boys, we were unable to perform the analysis by sex owing to difficulty recruiting enough female patients. Other limitations include the need to perform test–retest assessment within the same individual and the relatively small sample size. Conclusion Two metabolites have potential as biomarkers for the clinical diagnosis and evaluation of autism. PMID:26395811

Cancer mortality in cohorts of workers in the European rubber manufacturing industry first employed since 1975.

PubMed

Boniol, M; Koechlin, A; Świątkowska, B; Sorahan, T; Wellmann, J; Taeger, D; Jakobsson, K; Pira, E; Boffetta, P; La Vecchia, C; Pizot, C; Boyle, P

2016-05-01

Increased cancer risk has been reported among workers in the rubber manufacturing industry employed before the 1960s. It is unclear whether risk remains increased among workers hired subsequently. The present study focused on risk of cancer mortality for rubber workers first employed since 1975 in 64 factories. Anonymized data from cohorts of rubber workers employed for at least 1 year from Germany, Italy, Poland, Sweden, and the UK were pooled. Standardized mortality ratios (SMRs), based on country-specific death rates, were reported for bladder and lung cancer (primary outcomes of interest), for other selected cancer sites, and for cancer sites with a minimum of 10 deaths in men or women. Analyses stratified by type of industry, period, and duration of employment were carried out. A total of 38 457 individuals (29 768 men; 8689 women) contributed to 949 370 person-years. No increased risk of bladder cancer was observed [SMR = 0.80, 95% confidence interval (CI) 0.46; 1.38]. The risk of lung cancer death was reduced (SMR = 0.81, 95% CI 0.70; 0.94). No statistically significant increased risk was observed for any other cause of death. A reduced risk was evident for total cancer mortality (SMR = 0.81, 95% CI 0.76; 0.87). Risks were lower for workers in the tyre industry compared with workers in the general rubber goods sector. Analysis by employment duration showed a negative trend with SMRs decreasing with increasing duration of employment. In an analysis of secondary end points, when stratified by type of industry and period of first employment, excess risks of myeloma and gastric cancer were observed each due, essentially, to results from one centre. No consistent increased risk of cancer death was observed among rubber workers first employed since 1975, no overall analysis of the pooled cohort produced significantly increased risk. Continued surveillance of the present cohorts is required to confirm the absence of long-term risk. © The Author 2016. 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.

Bivalirudin versus heparin in primary PCI: clinical outcomes and cost analysis

PubMed Central

Deharo, Pierre; Johnson, Thomas W; Rahbi, Hazim; Kandan, Raveen; Bowles, Ruth; Mozid, Abdul; Dorman, Stephen; Strange, Julian W; Baumbach, Andreas

2018-01-01

Background The evidence for benefits of bivalirudin over heparin has recently been challenged. We aimed to analyse the safety and cost-effectiveness following reintroduction of heparin instead of bivalirudin as the standard anticoagulation for primary percutaneous coronary intervention (PPCI) in a high-volume centre. Methods and results This analysis was an open-label, prospective registry including all patients admitted to our centre for PPCI from April 2014 to April 2016. Heparin was reintroduced as standard anticoagulant in April 2015. During the 2 years, 1291 patients underwent a PPCI, 662 in the Bivalirudin protocol period (Cohort B) and 629 in the Heparin protocol period (Cohort H). Baseline and procedural characteristics were not significantly different, except for a higher use of thromboaspiration and femoral access in the earlier Cohort B. Glycoprotein 2b3a (Gp2b3a) antagonists were used in 24% of the patients in Cohort B versus 28% in Cohort H (P<0.01). We did not observe any differences in death at 180 days (11.03% in Cohort B vs 11.29% in Cohort H)(HR 95% CI 0.98 (0.72 to 1.33), P=0.88). The incidence of any bleeding complications at 30 days did not differ between the two periods (21.9% vs 21.9%, P=0.99). The cost related to the anticoagulants amounted to £246 236 in Cohort B versus £4483 in Cohort H (£324 406 vs £102 347 when adding Gp2b3a antagonists). Conclusion We did not find clinically relevant changes in patient outcomes, including bleeding complications with reintroduction of heparin in our PPCI protocol. However, the use of heparin was associated with a major reduction in treatment costs. PMID:29765614

Trends in oral cavity, pharyngeal, oesophageal and gastric cancer mortality rates in Spain, 1952–2006: an age-period-cohort analysis

PubMed Central

2014-01-01

Background Although oral cavity, pharyngeal, oesophageal and gastric cancers share some risk factors, no comparative analysis of mortality rate trends in these illnesses has been undertaken in Spain. This study aimed to evaluate the independent effects of age, death period and birth cohort on the mortality rates of these tumours. Methods Specific and age-adjusted mortality rates by tumour and sex were analysed. Age-period-cohort log-linear models were fitted separately for each tumour and sex, and segmented regression models were used to detect changes in period- and cohort-effect curvatures. Results Among men, the period-effect curvatures for oral cavity/pharyngeal and oesophageal cancers displayed a mortality trend that rose until 1995 and then declined. Among women, oral cavity/pharyngeal cancer mortality increased throughout the study period whereas oesophageal cancer mortality decreased after 1970. Stomach cancer mortality decreased in both sexes from 1965 onwards. Lastly, the cohort-effect curvature showed a certain degree of similarity for all three tumours in both sexes, which was greater among oral cavity, pharyngeal and oesophageal cancers, with a change point in evidence, after which risk of death increased in cohorts born from the 1910-1920s onwards and decreased among the 1950–1960 cohorts and successive generations. This latter feature was likewise observed for stomach cancer. Conclusions While the similarities of the cohort effects in oral cavity/pharyngeal, oesophageal and gastric tumours support the implication of shared risk factors, the more marked changes in cohort-effect curvature for oral cavity/pharyngeal and oesophageal cancer could be due to the greater influence of some risk factors in their aetiology, such as smoking and alcohol consumption. The increase in oral cavity/pharyngeal cancer mortality in women deserves further study. PMID:24725381

Trends in oral cavity, pharyngeal, oesophageal and gastric cancer mortality rates in Spain, 1952-2006: an age-period-cohort analysis.

PubMed

Seoane-Mato, Daniel; Aragonés, Nuria; Ferreras, Eva; García-Pérez, Javier; Cervantes-Amat, Marta; Fernández-Navarro, Pablo; Pastor-Barriuso, Roberto; López-Abente, Gonzalo

2014-04-11

Although oral cavity, pharyngeal, oesophageal and gastric cancers share some risk factors, no comparative analysis of mortality rate trends in these illnesses has been undertaken in Spain. This study aimed to evaluate the independent effects of age, death period and birth cohort on the mortality rates of these tumours. Specific and age-adjusted mortality rates by tumour and sex were analysed. Age-period-cohort log-linear models were fitted separately for each tumour and sex, and segmented regression models were used to detect changes in period- and cohort-effect curvatures. Among men, the period-effect curvatures for oral cavity/pharyngeal and oesophageal cancers displayed a mortality trend that rose until 1995 and then declined. Among women, oral cavity/pharyngeal cancer mortality increased throughout the study period whereas oesophageal cancer mortality decreased after 1970. Stomach cancer mortality decreased in both sexes from 1965 onwards. Lastly, the cohort-effect curvature showed a certain degree of similarity for all three tumours in both sexes, which was greater among oral cavity, pharyngeal and oesophageal cancers, with a change point in evidence, after which risk of death increased in cohorts born from the 1910-1920s onwards and decreased among the 1950-1960 cohorts and successive generations. This latter feature was likewise observed for stomach cancer. While the similarities of the cohort effects in oral cavity/pharyngeal, oesophageal and gastric tumours support the implication of shared risk factors, the more marked changes in cohort-effect curvature for oral cavity/pharyngeal and oesophageal cancer could be due to the greater influence of some risk factors in their aetiology, such as smoking and alcohol consumption. The increase in oral cavity/pharyngeal cancer mortality in women deserves further study.

Postoperative radiotherapy and tumor recurrence after complete resection of stage II/III thymic tumor: a meta-analysis of cohort studies.

PubMed

Ma, Jietao; Sun, Xin; Huang, Letian; Xiong, Zhicheng; Yuan, Meng; Zhang, Shuling; Han, Cheng-Bo

2016-01-01

Whether postoperative radiotherapy (PORT) is effective for reducing the recurrence risk in patients who received complete resection of the stage II or III thymic tumors has not been determined. A meta-analysis was performed by combining the results of all available controlled trials. PubMed, Cochrane's Library, and the Embase databases were searched for studies which compared the recurrence data for patients with complete resection of the stage II or III thymic tumors assigned to an observing group, or a PORT group. A random effect model was applied to combine the results. Nineteen studies, all designed as retrospective cohort studies were included. These studies included 663 patients of PORT group and 617 patients of observing group. The recurrence rate for the patients in PORT group and observing group were 12.4% and 11.5%, respectively. Results of our study indicated that PORT has no significant influence on recurrent risk in patients with stage II or III thymic tumor after complete resection (odds ratio 1.02, 95% confidence interval 0.55-1.90, P=0.96). When stratified by stages, our meta-analyses did not indicate any significant effects of PORT on recurrent outcomes in either the stage II or the stage III patients. Moreover, subsequent analysis limited to studies only including patients with thymoma or thymic carcinoma also did not support the benefits of PORT on recurrent outcomes. Although derived from retrospective cohort studies, current evidence did not support any benefit of PORT on recurrent risk in patients with complete resection of the stage II or III thymic tumors.

Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts.

PubMed

Mozaffarian, Dariush; Dashti, Hassan S; Wojczynski, Mary K; Chu, Audrey Y; Nettleton, Jennifer A; Männistö, Satu; Kristiansson, Kati; Reedik, Mägi; Lahti, Jari; Houston, Denise K; Cornelis, Marilyn C; van Rooij, Frank J A; Dimitriou, Maria; Kanoni, Stavroula; Mikkilä, Vera; Steffen, Lyn M; de Oliveira Otto, Marcia C; Qi, Lu; Psaty, Bruce; Djousse, Luc; Rotter, Jerome I; Harald, Kennet; Perola, Markus; Rissanen, Harri; Jula, Antti; Krista, Fischer; Mihailov, Evelin; Feitosa, Mary F; Ngwa, Julius S; Xue, Luting; Jacques, Paul F; Perälä, Mia-Maria; Palotie, Aarno; Liu, Yongmei; Nalls, Nike A; Ferrucci, Luigi; Hernandez, Dena; Manichaikul, Ani; Tsai, Michael Y; Kiefte-de Jong, Jessica C; Hofman, Albert; Uitterlinden, André G; Rallidis, Loukianos; Ridker, Paul M; Rose, Lynda M; Buring, Julie E; Lehtimäki, Terho; Kähönen, Mika; Viikari, Jorma; Lemaitre, Rozenn; Salomaa, Veikko; Knekt, Paul; Metspalu, Andres; Borecki, Ingrid B; Cupples, L Adrienne; Eriksson, Johan G; Kritchevsky, Stephen B; Bandinelli, Stefania; Siscovick, David; Franco, Oscar H; Deloukas, Panos; Dedoussis, George; Chasman, Daniel I; Raitakari, Olli; Tanaka, Toshiko

2017-01-01

Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA. These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.

Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts

PubMed Central

Dashti, Hassan S; Wojczynski, Mary K; Chu, Audrey Y; Nettleton, Jennifer A; Männistö, Satu; Kristiansson, Kati; Reedik, Mägi; Lahti, Jari; Houston, Denise K; Cornelis, Marilyn C; van Rooij, Frank J. A; Dimitriou, Maria; Kanoni, Stavroula; Mikkilä, Vera; Steffen, Lyn M; de Oliveira Otto, Marcia C; Qi, Lu; Psaty, Bruce; Djousse, Luc; Rotter, Jerome I; Harald, Kennet; Perola, Markus; Rissanen, Harri; Jula, Antti; Krista, Fischer; Mihailov, Evelin; Feitosa, Mary F; Ngwa, Julius S; Xue, Luting; Jacques, Paul F; Perälä, Mia-Maria; Palotie, Aarno; Liu, Yongmei; Nalls, Nike A; Ferrucci, Luigi; Hernandez, Dena; Manichaikul, Ani; Tsai, Michael Y; Kiefte-de Jong, Jessica C; Hofman, Albert; Uitterlinden, André G; Rallidis, Loukianos; Ridker, Paul M; Rose, Lynda M; Buring, Julie E; Lehtimäki, Terho; Kähönen, Mika; Viikari, Jorma; Lemaitre, Rozenn; Salomaa, Veikko; Knekt, Paul; Metspalu, Andres; Borecki, Ingrid B; Cupples, L. Adrienne; Eriksson, Johan G; Kritchevsky, Stephen B; Bandinelli, Stefania; Siscovick, David; Franco, Oscar H; Deloukas, Panos; Dedoussis, George; Chasman, Daniel I; Raitakari, Olli; Tanaka, Toshiko

2017-01-01

Background Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. Objective To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. Design We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. Results Heritability estimates for fish and EPA+DHA consumption ranged from 0.13–0.24 and 0.12–0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (FreqA = 0.015) was associated with 0.029 servings/day (~1 serving/month) lower fish consumption (P = 1.96x10-8). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10-7). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA. Conclusions These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation. PMID:29236708

Consumption of whole grains in relation to mortality from all causes, cardiovascular disease, and diabetes

PubMed Central

Li, Bailing; Zhang, Guanxin; Tan, Mengwei; Zhao, Libo; Jin, Lei; Tang, Xiaojun; Jiang, Gengxi; Zhong, Keng

2016-01-01

Abstract Background: To investigate the correlation between consumption of whole grains and the risk of all-cause, cardiovascular disease (CVD), and diabetes-specific mortality according to a dose–response meta-analysis of prospective cohort studies. Methods: Observational cohort studies, which reported associations between whole grains and the risk of death outcomes, were identified by searching articles in the MEDLINE, EMBASE, and the reference lists of relevant articles. The search was up to November 30, 2015. Data extraction was performed by 2 independent investigators, and a consensus was reached with involvement of a third. Results: Ten prospective cohort studies (9 publications) were eligible in this meta-analysis. During follow-up periods ranging from 5.5 to 26 years, there were 92,647 deaths among 782,751 participants. Overall, a diet containing greater amounts of whole grains may be associated with a lower risk of all-cause, CVD-, and coronary heart disease (CHD)-specific mortality. The summary relative risks (RRs) were 0.93 (95% confidence intervals [CIs]: 0.91–0.95; Pheterogeneity < 0.001) for all-cause mortality, 0.95 (95% CIs: 0.92–0.98; Pheterogeneity < 0.001) for CVD-specific mortality, and 0.92 (95% CIs: 0.88–0.97; Pheterogeneity < 0.001) for CHD-specific mortality for an increment of 1 serving (30 g) a day of whole grain intake. The combined estimates were robust across subgroup and sensitivity analyses. Higher consumption of whole grains was not appreciably associated with risk of mortality from stroke and diabetes. Conclusion: Evidence from observational cohort studies indicates inverse associations of intake of whole grains with risk of mortality from all-cause, CVD, and CHD. However, no associations with risk of deaths from stroke and diabetes were observed. PMID:27537552

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

Immortal time bias: a frequently unrecognized threat to validity in the evaluation of postoperative radiotherapy.

PubMed

Park, Henry S; Gross, Cary P; Makarov, Danil V; Yu, James B

2012-08-01

To evaluate the influence of immortal time bias on observational cohort studies of postoperative radiotherapy (PORT) and the effectiveness of sequential landmark analysis to account for this bias. First, we reviewed previous studies of the Surveillance, Epidemiology, and End Results (SEER) database to determine how frequently this bias was considered. Second, we used SEER to select three tumor types (glioblastoma multiforme, Stage IA-IVM0 gastric adenocarcinoma, and Stage II-III rectal carcinoma) for which prospective trials demonstrated an improvement in survival associated with PORT. For each tumor type, we calculated conditional survivals and adjusted hazard ratios of PORT vs. postoperative observation cohorts while restricting the sample at sequential monthly landmarks. Sixty-two percent of previous SEER publications evaluating PORT failed to use a landmark analysis. As expected, delivery of PORT for all three tumor types was associated with improved survival, with the largest associated benefit favoring PORT when all patients were included regardless of survival. Preselecting a cohort with a longer minimum survival sequentially diminished the apparent benefit of PORT. Although the majority of previous SEER articles do not correct for it, immortal time bias leads to altered estimates of PORT effectiveness, which are very sensitive to landmark selection. We suggest the routine use of sequential landmark analysis to account for this bias. Copyright © 2012 Elsevier Inc. All rights reserved.

Immortal Time Bias: A Frequently Unrecognized Threat to Validity in the Evaluation of Postoperative Radiotherapy

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

Park, Henry S.; Gross, Cary P.; Makarov, Danil V.

2012-08-01

Purpose: To evaluate the influence of immortal time bias on observational cohort studies of postoperative radiotherapy (PORT) and the effectiveness of sequential landmark analysis to account for this bias. Methods and Materials: First, we reviewed previous studies of the Surveillance, Epidemiology, and End Results (SEER) database to determine how frequently this bias was considered. Second, we used SEER to select three tumor types (glioblastoma multiforme, Stage IA-IVM0 gastric adenocarcinoma, and Stage II-III rectal carcinoma) for which prospective trials demonstrated an improvement in survival associated with PORT. For each tumor type, we calculated conditional survivals and adjusted hazard ratios of PORTmore » vs. postoperative observation cohorts while restricting the sample at sequential monthly landmarks. Results: Sixty-two percent of previous SEER publications evaluating PORT failed to use a landmark analysis. As expected, delivery of PORT for all three tumor types was associated with improved survival, with the largest associated benefit favoring PORT when all patients were included regardless of survival. Preselecting a cohort with a longer minimum survival sequentially diminished the apparent benefit of PORT. Conclusions: Although the majority of previous SEER articles do not correct for it, immortal time bias leads to altered estimates of PORT effectiveness, which are very sensitive to landmark selection. We suggest the routine use of sequential landmark analysis to account for this bias.« less

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.

Jim Crow and premature mortality among the US Black and White population, 1960-2009: an age-period-cohort analysis.

PubMed

Krieger, Nancy; Chen, Jarvis T; Coull, Brent A; Beckfield, Jason; Kiang, Mathew V; Waterman, Pamela D

2014-07-01

Scant research has analyzed the health impact of abolition of Jim Crow (ie, legal racial discrimination overturned by the US 1964 Civil Rights Act). We used hierarchical age-period-cohort models to analyze US national black and white premature mortality rates (death before 65 years of age) in 1960-2009. Within a context of declining US black and white premature mortality rates and a persistent 2-fold excess black risk of premature mortality in both the Jim Crow and non-Jim Crow states, analyses including random period, cohort, state, and county effects and fixed county income effects found that, within the black population, the largest Jim Crow-by-period interaction occurred in 1960-1964 (mortality rate ratio [MRR] = 1.15 [95% confidence interval = 1.09-1.22), yielding the largest overall period-specific Jim Crow effect MRR of 1.27, with no such interactions subsequently observed. Furthermore, the most elevated Jim Crow-by-cohort effects occurred for birth cohorts from 1901 through 1945 (MRR range = 1.05-1.11), translating to the largest overall cohort-specific Jim Crow effect MRRs for the 1921-1945 birth cohorts (MRR ~ 1.2), with no such interactions subsequently observed. No such interactions between Jim Crow and either period or cohort occurred among the white population. Together, the study results offer compelling evidence of the enduring impact of both Jim Crow and its abolition on premature mortality among the US black population, although insufficient to eliminate the persistent 2-fold black excess risk evident in both the Jim Crow and non-Jim Crow states from 1960 to 2009.

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

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.

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.

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.

Smoking and physical inactivity increase cancer prevalence in BRCA-1 and BRCA-2 mutation carriers: results from a retrospective observational analysis.

PubMed

Grill, Sabine; Yahiaoui-Doktor, Maryam; Dukatz, Ricarda; Lammert, Jacqueline; Ullrich, Mirjam; Engel, Christoph; Pfeifer, Katharina; Basrai, Maryam; Siniatchkin, Michael; Schmidt, Thorsten; Weisser, Burkhard; Rhiem, Kerstin; Ditsch, Nina; Schmutzler, Rita; Bischoff, Stephan C; Halle, Martin; Kiechle, Marion

2017-12-01

The aim of this analysis in a pilot study population was to investigate whether we can verify seemingly harmful lifestyle factors such as nicotine and alcohol indulgence, obesity, and physical inactivity, as well as a low socioeconomic status for increased cancer prevalence in a cohort of BRCA 1 and 2 mutation carriers. The analysis data are derived from 68 participants of the lifestyle intervention study LIBRE-1, a randomized, prospective trial that aimed to test the feasibility of a lifestyle modification in BRCA 1 and 2 mutation carriers. At study entry, factors such as medical history, lifestyle behavior, and socioeconomic status were retrospectively documented by interview and the current BMI was determined by clinical examination. The baseline measurements were compared within the cohort, and presented alongside reference values for the German population. Study participants indicating a higher physical activity during their adolescence showed a significantly lower cancer prevalence (p = 0.019). A significant difference in cancer occurrence was observed in those who smoked prior to the disease, and those who did not smoke (p < 0.001). Diseased mutation carriers tended to have a lower BMI compared to non-diseased mutation carriers (p = 0.079), whereas non-diseased revealed a significantly higher physical activity level than diseased mutation carriers (p = 0.046). The present data in this small cohort of 68 mutation carriers suggest that smoking and low physical activity during adolescence are risk factors for developing breast cancer in women with BRCA1 or BRCA2 mutation. Further data of the ongoing LIBRE 2 study are necessary to confirm these findings in a larger cohort of 600 mutation carriers.

Cohort Profile: The JS High School study (JSHS): a cohort study of Korean adolescents.

PubMed

Choi, Dong Phil; Lee, Joo Young; Kim, Hyeon Chang

2017-04-01

Major aetiologies of atherosclerotic cardiovascular diseases begin in childhood and atherosclerotic vascular abnormalities can be observed among children and adolescents. Adolescent cohort studies have important advantages because they can observe earlier changes in vascular structure and function. The purpose of the JS High School study (JSHS) is to identify biomarkers predicting or indicating early structural and functional vascular change in adolescents. The JSHS is a prospective cohort study of a Korean adolescent population. The target population of the JSHS was first-graders (aged 14 to17 years) at a high school of South Korea. Enrolment and baseline examinations were conducted in years 2007, 2010, 2011 and 2012. Among the total eligible population of 1115 students, 1071 (96.1%) participated in the study and completed all baseline examinations. Informed consent forms were obtained from each participant and his/her parent or guardian. Baseline examinations include: questionnaires on demographics, health behaviours, medical history, and depression symptoms; fasting blood analysis; anthropometric measurement; body impedance analysis; blood pressure measurement; radial artery tonometry; bone densitometry; pulmonary function tests; and carotid ultrasonography. Participants enrolled from 2007 through 2012 were re-examined after 30 months of follow-up, and those who enrolled in 2012 were re-examined after 24 months of follow-up. The corresponding author may be contacted for potential collaboration and data access. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Genotyping of the Alzheimer's Disease Genome-Wide Association Study Index Single Nucleotide Polymorphisms in the Brains for Dementia Research Cohort.

PubMed

Brookes, Keeley J; McConnell, George; Williams, Kirsty; Chaudhury, Sultan; Madhan, Gaganjit; Patel, Tulsi; Turley, Christopher; Guetta-Baranes, Tamar; Bras, Jose; Guerreiro, Rita; Hardy, John; Francis, Paul T; Morgan, Kevin

2018-06-08

The Brains for Dementia Research project is a recently established longitudinal cohort which aims to provide brain tissue for research purposes from neuropathologically defined samples. Here we present the findings from our analysis on the 19 established GWAS index SNPs for Alzheimer's disease, in order to demonstrate if the BDR sample also displays association to these variants. A highly significant association of the APOEɛ4 allele was identified (p = 3.99×10-12). Association tests for the 19 GWAS SNPs found that although no SNPs survive multiple testing, nominal significant findings were detected and concordance with the Lambert et al. GWAS meta-analysis was observed.

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.

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.

Education and fertility decline in China during transitional times: A cohort approach.

PubMed

Piotrowski, Martin; Tong, Yuying

2016-01-01

We examine the effect of education on birth outcomes in China during the period of economic transition and large-scale changes in mass education and population control measures. Retrospective micro data from the 2008 Chinese General Social Survey and discrete time event history analysis are used to examine the fertility history of several cohorts of women born between 1945 and 1968. We observed births at different parities, distinguishing the education effect across cohorts and rural/urban sectors. We found differences across cohorts consistent with unique features of the Chinese context, such as the radical egalitarian era of educational expansion, and the Reform Era. We also found that despite the increase in some education levels across cohorts (e.g., junior high school in rural areas), birth chances were more likely to be concentrated among less educated women, suggesting the impact of factors related to returns to education and hence the desire for children. Copyright © 2015 Elsevier Inc. All rights reserved.

The STK33-linked SNP rs4929949 is associated with obesity and BMI in two independent cohorts of Swedish and Greek children.

PubMed

Rask-Andersen, Mathias; Moschonis, George; Chrousos, George P; Marcus, Claude; Dedoussis, George V; Fredriksson, Robert; Schiöth, Helgi B

2013-01-01

Recent genome wide association studies (GWAS) have identified a locus on chromosome 11p15.5, closely associated with serine/threonine kinase 33 (STK33), to be associated with body mass. STK33, a relatively understudied protein, has been linked to KRAS mutation-driven cancers and explored as a potential antineoplastic drug target. The strongest association with body mass observed at this loci in GWAS was rs4929949, a single nucleotide polymorphism located within intron 1 of the gene encoding STK33. The functional implications of rs4929949 or related variants have not been explored as of yet. We have genotyped rs4929949 in two cohorts, an obesity case-control cohort of 991 Swedish children, and a cross-sectional cohort of 2308 Greek school children. We found that the minor allele of rs4929949 was associated with obesity in the cohort of Swedish children and adolescents (OR = 1.199 (95%CI: 1.002-1.434), p = 0.047), and with body mass in the cross-sectional cohort of Greek children (β = 0.08147 (95% CI: 0.1345-0.1618), p = 0.021). We observe the effects of rs4929949 on body mass to be detectable already at adolescence. Subsequent analysis did not detect any association of rs4929949 to phenotypic measurements describing body adiposity or to metabolic factors such as insulin levels, triglycerides and insulin resistance (HOMA).

The STK33-Linked SNP rs4929949 Is Associated with Obesity and BMI in Two Independent Cohorts of Swedish and Greek Children

PubMed Central

Rask-Andersen, Mathias; Moschonis, George; Chrousos, George P.; Marcus, Claude; Dedoussis, George V.; Fredriksson, Robert; Schiöth, Helgi B.

2013-01-01

Recent genome wide association studies (GWAS) have identified a locus on chromosome 11p15.5, closely associated with serine/threonine kinase 33 (STK33), to be associated with body mass. STK33, a relatively understudied protein, has been linked to KRAS mutation-driven cancers and explored as a potential antineoplastic drug target. The strongest association with body mass observed at this loci in GWAS was rs4929949, a single nucleotide polymorphism located within intron 1 of the gene encoding STK33. The functional implications of rs4929949 or related variants have not been explored as of yet. We have genotyped rs4929949 in two cohorts, an obesity case-control cohort of 991 Swedish children, and a cross-sectional cohort of 2308 Greek school children. We found that the minor allele of rs4929949 was associated with obesity in the cohort of Swedish children and adolescents (OR = 1.199 (95%CI: 1.002–1.434), p = 0.047), and with body mass in the cross-sectional cohort of Greek children (β = 0.08147 (95% CI: 0.1345–0.1618), p = 0.021). We observe the effects of rs4929949 on body mass to be detectable already at adolescence. Subsequent analysis did not detect any association of rs4929949 to phenotypic measurements describing body adiposity or to metabolic factors such as insulin levels, triglycerides and insulin resistance (HOMA). PMID:23967198

Age-period-cohort analysis of hepatitis A incidence rates in Korea from 2002 to 2012

PubMed Central

2016-01-01

OBJECTIVES This study aimed to evaluate the epidemiology of hepatitis A in Korea from 2002 to 2012 using age-period-cohort analyses. METHODS We used claims data from the Korean National Health Insurance Corporation for the entire population. Census data from 2010 were used as the standard population. The incidence of hepatitis A was assumed to have a Poisson distribution, and the models and effects were evaluated using the intrinsic estimator method, the likelihood ratio, and the Akaike information criterion. RESULTS The incidence of hepatitis A gradually increased until 2007 (from 17.55 to 35.72 per 100,000 population) and peaked in 2009 (177.47 per 100,000 population). The highest incidence was observed among 27-29-year-old individuals when we omitted data from 2005 to 2007. From 2005 to 2007, the peak incidence was observed among 24-26-year-old individuals, followed by 27-29-year-olds. The best model fits were observed when the age-period-cohort variables were all considered at the same time for males, females, and the whole population. CONCLUSIONS The incidence of hepatitis A exhibited significant age-period-cohort effects; its incidence peaked in 2009 and was especially high among Koreans 20-39 years of age. These epidemiological patterns may help predict when high incidence rates of hepatitis A may occur in developing countries during their socioeconomic development. PMID:27703127

Age-period-cohort analysis of hepatitis A incidence rates in Korea from 2002 to 2012.

PubMed

Seo, Joo Yeon; Choi, Sungyong; Choi, BoYoul; Ki, Moran

2016-01-01

This study aimed to evaluate the epidemiology of hepatitis A in Korea from 2002 to 2012 using age-period-cohort analyses. We used claims data from the Korean National Health Insurance Corporation for the entire population. Census data from 2010 were used as the standard population. The incidence of hepatitis A was assumed to have a Poisson distribution, and the models and effects were evaluated using the intrinsic estimator method, the likelihood ratio, and the Akaike information criterion. The incidence of hepatitis A gradually increased until 2007 (from 17.55 to 35.72 per 100,000 population) and peaked in 2009 (177.47 per 100,000 population). The highest incidence was observed among 27-29-year-old individuals when we omitted data from 2005 to 2007. From 2005 to 2007, the peak incidence was observed among 24-26-year-old individuals, followed by 27-29-year-olds. The best model fits were observed when the age-period-cohort variables were all considered at the same time for males, females, and the whole population. The incidence of hepatitis A exhibited significant age-period-cohort effects; its incidence peaked in 2009 and was especially high among Koreans 20-39 years of age. These epidemiological patterns may help predict when high incidence rates of hepatitis A may occur in developing countries during their socioeconomic development.

Mortality amongst Paris fire-fighters.

PubMed

Deschamps, S; Momas, I; Festy, B

1995-12-01

This paper is the first mortality cohort study undertaken in France to examine the association between fire-fighting and cause of death. The cohort investigated in this study consisted of 830 male members of the Brigade des sapeurs-pompiers de Paris (BSPP). These professional had served for a minimum of 5 years on 1 January 1977. They were monitored for a 14 year period, finishing 1 January 1991. When compared to the average French male, the Paris fire-fighters were found to have a far lower overall mortality (SMR = 0.52 [0.35-0.75]). None of the cause specific SMRs were significantly different from unity. However a greater number of deaths than expected was observed for genito-urinary cancer (SMR = 3.29), digestive cancer (SMR = 1.14), respiratory cancer (SMR = 1.12) and 'cerebrovascular disease' (SMR = 1.16). The low overall SMR observed was consistent with the healthy worker effect. As for cause specific SMRs, they will be confirmed or invalidated by a further analysis as the follow-up of this cohort is being carried on.

Use of atomoxetine and suicidal ideation in children and adolescents: Results of an observational cohort study within general practice in England.

PubMed

Davies, M; Coughtrie, A; Layton, D; Shakir, S A S

2017-01-01

To investigate the association between atomoxetine, a drug used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and suicidal ideation, within a cohort of 2-18-year-old patients in England. The study was conducted using the observational cohort technique of Modified prescription event monitoring (M-PEM). Patients prescribed atomoxetine were identified from dispensed prescriptions issued by primary care physicians. A customised postal GP questionnaire was used to capture outcome data for suicidal ideation. A matched pair cohort analysis was performed within patients to compare the risk of suicidal ideation in the period after starting atomoxetine with the risk prior to starting atomoxetine; this was stratified by age and concomitant use of methylphenidate. Additional information on patient characteristics, and events of interest was also collected; individual cases of suicidal ideation were qualitatively assessed for drug relatedness. Of the final cohort (n=4509); 85.5% male (n=3857), median age 11 years (IQR: 9,14). Primary prescribing indication for atomoxetine was ADHD (n=4261, 94.6%). Almost a quarter of the cohort had been co-prescribed methylphenidate. Results of the matched pair cohort analysis indicated that the period after starting atomoxetine was not associated with an increase in the incidence of suicidal ideation compared to the period prior to starting treatment (RR: 0.71; CI: 0.48-1.07; P-value: 0.104). Individual case assessment of suicidal ideation suggested a causal association within a number of cases. This study found no evidence of an increased risk of suicidal ideation during treatment with atomoxetine, compared to the period prior to starting treatment. Amongst age specific subgroups, this risk may change. Nonetheless, individual case assessment suggested a causal relationship in some patients, hence physicians need to be aware of the possibility of developing this event, and furthermore consider how best to detect it in this paediatric population. This study demonstrates the importance of combining quantitative statistical analyses with a qualitative case series assessment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Antidepressant use and risk of coronary heart disease: meta-analysis of observational studies

PubMed Central

Oh, Seung-Won; Kim, Joonseok; Myung, Seung-Kwon; Hwang, Seung-Sik; Yoon, Dae-Hyun

2014-01-01

Aims Our goal was to evaluate the association between antidepressant use and the risk of coronary heart disease (CHD) among subjects with no history of coronary heart disease. Methods A search of Medline, EMBASE, PsycINFO and the Cochrane Library was performed in January 2013. Two authors independently reviewed and selected eligible observational studies, based on predetermined selection criteria. Pooled relative risks (RRs) with confidence intervals (CIs) were calculated using random-effects or fixed-effects models. Results Sixteen observational studies (seven case–control studies and nine cohort studies) were included in the final analysis. There was no association between selective serotonin reuptake inhibitor use and the risk of CHD overall [odds ratio (OR), 0.93; 95% CI, 0.65–1.33] or in subgroup meta-analysis of case–control studies (OR, 0.91; 95% CI, 0.60–1.37) and cohort studies (RR, 0.96; 95% CI, 0.59–1.55). The use of tricyclic antidepressant was associated with an increased risk of CHD overall (OR, 1.51; 95% CI, 1.07–2.12), but it was observed only in case–control studies (OR, 1.56; 95% CI, 1.24–1.96) and low-quality studies (OR, 1.49; 95% CI, 1.20–1.85) in the subgroup meta-analyses. Conclusions This meta-analysis of observational studies in subjects with no history of CHD suggests that neither selective serotonin reuptake inhibitor nor tricyclic antidepressant use is associated with an increased risk of CHD. PMID:24646010

A biregional survey and review of first-line treatment failure and second-line paediatric antiretroviral access and use in Asia and southern Africa

PubMed Central

2011-01-01

Background To better understand the need for paediatric second-line antiretroviral therapy (ART), an ART management survey and a cross-sectional analysis of second-line ART use were conducted in the TREAT Asia Paediatric HIV Observational Database and the IeDEA Southern Africa (International Epidemiologic Databases to Evaluate AIDS) regional cohorts. Methods Surveys were conducted in April 2009. Analysis data from the Asia cohort were collected in March 2009 from 12 centres in Cambodia, India, Indonesia, Malaysia, and Thailand. Data from the IeDEA Southern Africa cohort were finalized in February 2008 from 10 centres in Malawi, Mozambique, South Africa and Zimbabwe. Results Survey responses reflected inter-regional variations in drug access and national guidelines. A total of 1301 children in the TREAT Asia and 4561 children in the IeDEA Southern Africa cohorts met inclusion criteria for the cross-sectional analysis. Ten percent of Asian and 3.3% of African children were on second-line ART at the time of data transfer. Median age (interquartile range) in months at second-line initiation was 120 (78-145) months in the Asian cohort and 66 (29-112) months in the southern African cohort. Regimens varied, and the then current World Health Organization-recommended nucleoside reverse transcriptase combination of abacavir and didanosine was used in less than 5% of children in each region. Conclusions In order to provide life-long ART for children, better use of current first-line regimens and broader access to heat-stable, paediatric second-line and salvage formulations are needed. There will be limited benefit to earlier diagnosis of treatment failure unless providers and patients have access to appropriate drugs for children to switch to. PMID:21306608

Trends in mouth cancer incidence in Mumbai, India (1995-2009): An age-period-cohort analysis.

PubMed

Shridhar, Krithiga; Rajaraman, Preetha; Koyande, Shravani; Parikh, Purvish M; Chaturvedi, Pankaj; Dhillon, Preet K; Dikshit, Rajesh P

2016-06-01

Despite tobacco control and health promotion efforts, the incidence rates of mouth cancer are increasing across most regions in India. Analysing the influence of age, time period and birth cohort on these secular trends can point towards underlying factors and help identify high-risk populations for improved cancer control programmes. We evaluated secular changes in mouth cancer incidence among men and women aged 25-74 years in Mumbai between 1995 and 2009 by calculating age-specific and age-standardized incidence rates (ASR). We estimated the age-adjusted linear trend for annual percent change (EAPC) using the drift parameter, and conducted an age-period-cohort (APC) analysis to quantify recent time trends and to evaluate the significance of birth cohort and calendar period effects. Over the 15-year period, age-standardized incidence rates of mouth cancer in men in Mumbai increased by 2.7% annually (95% CI:1.9 to 3.4), p<0.0001) while rates among women decreased (EAPC=-0.01% (95% CI:-0.02 to -0.002), p=0.03). APC analysis revealed significant non-linear positive period and cohort effects in men, with higher effects among younger men (25-49 years). Non-significant increasing trends were observed in younger women (25-49 years). APC analyses from the Mumbai cancer registry indicate a significant linear increase of mouth cancer incidence from 1995 to 2009 in men, which was driven by younger men aged 25-49 years, and a non-significant upward trend in similarly aged younger women. Health promotion efforts should more effectively target younger cohorts. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

No association of SORL1 SNPs with Alzheimer’s disease

PubMed Central

Minster, Ryan L.; DeKosky, Steven T.; Kamboh, M. Ilyas

2008-01-01

SORL1 is an element of the amyloid precursor protein processing pathway and is therefore a good candidate for affecting Alzheimer’s disease (AD) risk. Indeed, there have been reports of associations between variation in SORL1 and AD risk. We examined six statistically significant single-nucleotide polymorphisms from the initial observation in a large Caucasian American case–controls cohort (1000 late-onset AD [LOAD] cases and 1000 older controls). Analysis of allele, genotype and haplotype frequencies revealed no association with LOAD risk in our cohort. PMID:18562096

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

PubMed

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

2017-06-06

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

Postoperative radiotherapy and tumor recurrence after complete resection of stage II/III thymic tumor: a meta-analysis of cohort studies

PubMed Central

Ma, Jietao; Sun, Xin; Huang, Letian; Xiong, Zhicheng; Yuan, Meng; Zhang, Shuling; Han, Cheng-Bo

2016-01-01

Background Whether postoperative radiotherapy (PORT) is effective for reducing the recurrence risk in patients who received complete resection of the stage II or III thymic tumors has not been determined. A meta-analysis was performed by combining the results of all available controlled trials. Methods PubMed, Cochrane’s Library, and the Embase databases were searched for studies which compared the recurrence data for patients with complete resection of the stage II or III thymic tumors assigned to an observing group, or a PORT group. A random effect model was applied to combine the results. Results Nineteen studies, all designed as retrospective cohort studies were included. These studies included 663 patients of PORT group and 617 patients of observing group. The recurrence rate for the patients in PORT group and observing group were 12.4% and 11.5%, respectively. Results of our study indicated that PORT has no significant influence on recurrent risk in patients with stage II or III thymic tumor after complete resection (odds ratio 1.02, 95% confidence interval 0.55–1.90, P=0.96). When stratified by stages, our meta-analyses did not indicate any significant effects of PORT on recurrent outcomes in either the stage II or the stage III patients. Moreover, subsequent analysis limited to studies only including patients with thymoma or thymic carcinoma also did not support the benefits of PORT on recurrent outcomes. Conclusion Although derived from retrospective cohort studies, current evidence did not support any benefit of PORT on recurrent risk in patients with complete resection of the stage II or III thymic tumors. PMID:27524907

Prediction of persistent hemodynamic depression after carotid angioplasty and stenting using artificial neural network model.

PubMed

Jeon, Jin Pyeong; Kim, Chulho; Oh, Byoung-Doo; Kim, Sun Jeong; Kim, Yu-Seop

2018-01-01

To assess and compare predictive factors for persistent hemodynamic depression (PHD) after carotid artery angioplasty and stenting (CAS) using artificial neural network (ANN) and multiple logistic regression (MLR) or support vector machines (SVM) models. A retrospective data set of patients (n=76) who underwent CAS from 2007 to 2014 was used as input (training cohort) to a back-propagation ANN using TensorFlow platform. PHD was defined when systolic blood pressure was less than 90mmHg or heart rate was less 50 beats/min that lasted for more than one hour. The resulting ANN was prospectively tested in 33 patients (test cohort) and compared with MLR or SVM models according to accuracy and receiver operating characteristics (ROC) curve analysis. No significant difference in baseline characteristics between the training cohort and the test cohort was observed. PHD was observed in 21 (27.6%) patients in the training cohort and 10 (30.3%) patients in the test cohort. In the training cohort, the accuracy of ANN for the prediction of PHD was 98.7% and the area under the ROC curve (AUROC) was 0.961. In the test cohort, the number of correctly classified instances was 32 (97.0%) using the ANN model. In contrast, the accuracy rate of MLR or SVM model was both 75.8%. ANN (AUROC: 0.950; 95% CI [confidence interval]: 0.813-0.996) showed superior predictive performance compared to MLR model (AUROC: 0.796; 95% CI: 0.620-0.915, p<0.001) or SVM model (AUROC: 0.885; 95% CI: 0.725-0.969, p<0.001). The ANN model seems to have more powerful prediction capabilities than MLR or SVM model for persistent hemodynamic depression after CAS. External validation with a large cohort is needed to confirm our results. Copyright © 2017. Published by Elsevier B.V.

Trends in ischemic heart disease mortality in Korea, 1985-2009: an age-period-cohort analysis.

PubMed

Lee, Hye Ah; Park, Hyesook

2012-09-01

Economic growth and development of medical technology help to improve the average life expectancy, but the western diet and rapid conversions to poor lifestyles lead an increasing risk of major chronic diseases. Coronary heart disease mortality in Korea has been on the increase, while showing a steady decline in the other industrialized countries. An age-period-cohort analysis can help understand the trends in mortality and predict the near future. We analyzed the time trends of ischemic heart disease mortality, which is on the increase, from 1985 to 2009 using an age-period-cohort model to characterize the effects of ischemic heart disease on changes in the mortality rate over time. All three effects on total ischemic heart disease mortality were statistically significant. Regarding the period effect, the mortality rate was decreased slightly in 2000 to 2004, after it had continuously increased since the late 1980s that trend was similar in both sexes. The expected age effect was noticeable, starting from the mid-60's. In addition, the age effect in women was more remarkable than that in men. Women born from the early 1900s to 1925 observed an increase in ischemic heart mortality. That cohort effect showed significance only in women. The future cohort effect might have a lasting impact on the risk of ischemic heart disease in women with the increasing elderly population, and a national prevention policy is need to establish management of high risk by considering the age-period-cohort effect.

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.

Polycystic ovary syndrome (PCOS) and the risk of coronary heart disease (CHD): a meta-analysis.

PubMed

Zhao, Luqian; Zhu, Zhigang; Lou, Huiling; Zhu, Guodong; Huang, Weimin; Zhang, Shaogang; Liu, Feng

2016-06-07

Some studies reported a significant association between polycystic ovary syndrome (PCOS) and risk of cardiovascular disease (CVD). However, the results are controversial. A systematic search was conducted in the PubMed, Science Direct, EMBASE, and Cochrane Library databases. Five case-control studies and 5 cohort studies were selected, involving a total of 104392 subjects in this meta-analysis. PCOS was significantly associated with the increased risk of CVD (OR = 1.30; 95% CI 1.09 - 1.56; P = 0.004). In the subgroup analysis of study design, both case-control studies and prospective cohort studies showed significant results (OR = 1.79; 95% CI 1.16 - 2.77; P = 0.009; OR = 1.20; 95% CI 1.06 - 1.37; P = 0.005), while retrospective cohort studies did not show positive result (OR = 0.91; 95% CI 0.60 - 1.40; P = 0.68). In a further stratified analysis by type of CVD, a significant association was found between PCOS and coronary heart disease (CHD) (OR = 1.44; 95% CI 1.13 - 1.84; P = 0.004). However, no significant association was observed between PCOS and myocardial infarction (MI) (OR = 1.01; 95% CI 0.68 - 1.51; P = 0.95). In conclusion, this meta-analysis suggested that PCOS is significantly associated with increased CHD risk.

Healthcare utilization and costs in persons with insomnia in a managed care population.

PubMed

Anderson, Louise H; Whitebird, Robin R; Schultz, Jennifer; McEvoy, Charlene E; Kreitzer, Mary Jo; Gross, Cynthia R

2014-05-01

To better understand the direct costs of insomnia. Our study aimed to compare healthcare costs and utilization of patients diagnosed with insomnia who received care in a managed care organization with a set of matched controls. Our observational, retrospective cohort study compared 7647 adults with an insomnia diagnosis with an equally sized matched cohort of health plan members without an insomnia diagnosis between 2003 and 2006. We also compared a subset of patients diagnosed with and treated for insomnia with those diagnosed with insomnia but not treated. A large Midwestern health plan with more than 600,000 members. Multivariate analysis was used to estimate the association between insomnia diagnosis and costs, controlling for covariates, in the baseline and follow-up periods. Although we cannot conclude a causal relationship between insomnia and healthcare costs, our analysis found that insomnia diagnosis was associated with 26% higher costs in the baseline and 46% in the 12 months after diagnosis. When comorbidities were recognized, the insomnia cohort had 80% higher costs, on average, than the matched control cohort. These outcomes suggest the need to look beyond the direct cost of insomnia to how its interaction with comorbid conditions drives healthcare cost and utilization.

Genome-wide association study of suicide attempts in mood disorder patients.

PubMed

Perlis, Roy H; Huang, Jie; Purcell, Shaun; Fava, Maurizio; Rush, A John; Sullivan, Patrick F; Hamilton, Steven P; McMahon, Francis J; Schulze, Thomas G; Schulze, Thomas; Potash, James B; Zandi, Peter P; Willour, Virginia L; Penninx, Brenda W; Boomsma, Dorret I; Vogelzangs, Nicole; Middeldorp, Christel M; Rietschel, Marcella; Nöthen, Markus; Cichon, Sven; Gurling, Hugh; Bass, Nick; McQuillin, Andrew; Hamshere, Marian; Craddock, Nick; Sklar, Pamela; Smoller, Jordan W

2010-12-01

Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation.

Genome-Wide Association Study of Suicide Attempts in Mood Disorder Patients

PubMed Central

Perlis, Roy H.; Huang, Jie; Purcell, Shaun; Fava, Maurizio; Rush, A. John; Sullivan, Patrick F.; Hamilton, Steven P.; McMahon, Francis J.; Schulze, Thomas; Potash, James B.; Zandi, Peter P.; Willour, Virginia L.; Penninx, Brenda W.; Boomsma, Dorret I.; Vogelzangs, Nicole; Middeldorp, Christel M.; Rietschel, Marcella; Nöthen, Markus; Cichon, Sven; Gurling, Hugh; Bass, Nick; McQuillin, Andrew; Hamshere, Marian; Craddock, Nick; Sklar, Pamela; Smoller, Jordan W.

2013-01-01

Objective Family and twin studies suggest that liability for suicide attempts is heritable and distinct from mood disorder susceptibility. The authors therefore examined the association between common genomewide variation and lifetime suicide attempts. Method The authors analyzed data on lifetime suicide attempts from genomewide association studies of bipolar I and II disorder as well as major depressive disorder. Bipolar disorder subjects were drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder cohort, the Wellcome Trust Case Control Consortium bipolar cohort, and the University College London cohort. Replication was pursued in the NIMH Genetic Association Information Network bipolar disorder project and a German clinical cohort. Depression subjects were drawn from the Sequential Treatment Alternatives to Relieve Depression cohort, with replication in the Netherlands Study of Depression and Anxiety/Netherlands Twin Register depression cohort. Results Strongest evidence of association for suicide attempt in bipolar disorder was observed in a region without identified genes (rs1466846); five loci also showed suggestive evidence of association. In major depression, strongest evidence of association was observed for a single nucleotide polymorphism in ABI3BP, with six loci also showing suggestive association. Replication cohorts did not provide further support for these loci. However, meta-analysis incorporating approximately 8,700 mood disorder subjects identified four additional regions that met the threshold for suggestive association, including the locus containing the gene coding for protein kinase C-epsilon, previously implicated in models of mood and anxiety. Conclusions The results suggest that inherited risk for suicide among mood disorder patients is unlikely to be the result of individual common variants of large effect. They nonetheless provide suggestive evidence for multiple loci, which merit further investigation. PMID:21041247

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

Similar fecal immunochemical test results in screening and referral colorectal cancer

PubMed Central

van Turenhout, Sietze T; van Rossum, Leo GM; Oort, Frank A; Laheij, Robert JF; van Rijn, Anne F; Terhaar sive Droste, Jochim S; Fockens, Paul; van der Hulst, René WM; Bouman, Anneke A; Jansen, Jan BMJ; Meijer, Gerrit A; Dekker, Evelien; Mulder, Chris JJ

2012-01-01

AIM: To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. METHODS: In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). RESULTS: One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mL vs 613 ± 368 ng/mL, P = 0.02). Tissue tumor stage (T stage) distribution was different between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mL vs 870 ± 258 ng/mL, P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). CONCLUSION: Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage. PMID:23082056

Feasibility and utility of applications of the common data model to multiple, disparate observational health databases

PubMed Central

Makadia, Rupa; Matcho, Amy; Ma, Qianli; Knoll, Chris; Schuemie, Martijn; DeFalco, Frank J; Londhe, Ajit; Zhu, Vivienne; Ryan, Patrick B

2015-01-01

Objectives To evaluate the utility of applying the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) across multiple observational databases within an organization and to apply standardized analytics tools for conducting observational research. Materials and methods Six deidentified patient-level datasets were transformed to the OMOP CDM. We evaluated the extent of information loss that occurred through the standardization process. We developed a standardized analytic tool to replicate the cohort construction process from a published epidemiology protocol and applied the analysis to all 6 databases to assess time-to-execution and comparability of results. Results Transformation to the CDM resulted in minimal information loss across all 6 databases. Patients and observations excluded were due to identified data quality issues in the source system, 96% to 99% of condition records and 90% to 99% of drug records were successfully mapped into the CDM using the standard vocabulary. The full cohort replication and descriptive baseline summary was executed for 2 cohorts in 6 databases in less than 1 hour. Discussion The standardization process improved data quality, increased efficiency, and facilitated cross-database comparisons to support a more systematic approach to observational research. Comparisons across data sources showed consistency in the impact of inclusion criteria, using the protocol and identified differences in patient characteristics and coding practices across databases. Conclusion Standardizing data structure (through a CDM), content (through a standard vocabulary with source code mappings), and analytics can enable an institution to apply a network-based approach to observational research across multiple, disparate observational health databases. PMID:25670757

Association between metabolic syndrome and bone fractures: a meta-analysis of observational studies.

PubMed

Sun, Kan; Liu, Jianmin; Lu, Nan; Sun, Hanxiao; Ning, Guang

2014-02-09

Emerging epidemiological evidence suggest an association between metabolic syndrome and fractures. However, whether metabolic syndrome is an independent risk or protective factor of fractures remains controversial. Our goal is to provide a quantitative assessment of the association between metabolic syndrome and bone fractures by conducting a meta-analysis of observational studies. The PubMed and Embase database were searched through to March 2013 to identify studies that met pre-established inclusion criteria. Reference lists of retrieved articles were also reviewed. Summary effect estimates with 95% confidence intervals (CI) were derived using a fixed or random effects model, depending on the heterogeneity of the included studies. Eight epidemiologic studies involving 39,938 participants were included in the meta-analysis. In overall analysis, metabolic syndrome was not associated with prevalent fractures [pooled odds ratio (OR) 0.93, 95% CI 0.84 - 1.03] in cross-sectional studies or incident fractures [pooled relative risk (RR) 0.88, 95% CI 0.37 - 2.12] in prospective cohort studies. No evidence of heterogeneity was found in cross-sectional studies (p = 0.786, I2 = 0.0%). A substantial heterogeneity was detected in cohort studies (p = 0.001, I2 = 85.7%). No indication of significant publication bias was found either from Begg's test or Egger's test. Estimates of total effects were substantially consistent in the sensitivity and stratification analyses. The present meta-analysis of observational studies suggests that the metabolic syndrome has no explicit effect on bone fractures.

Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis.

PubMed

Adam, Martin; Schikowski, Tamara; Carsin, Anne Elie; Cai, Yutong; Jacquemin, Benedicte; Sanchez, Margaux; Vierkötter, Andrea; Marcon, Alessandro; Keidel, Dirk; Sugiri, Dorothee; Al Kanani, Zaina; Nadif, Rachel; Siroux, Valérie; Hardy, Rebecca; Kuh, Diana; Rochat, Thierry; Bridevaux, Pierre-Olivier; Eeftens, Marloes; Tsai, Ming-Yi; Villani, Simona; Phuleria, Harish Chandra; Birk, Matthias; Cyrys, Josef; Cirach, Marta; de Nazelle, Audrey; Nieuwenhuijsen, Mark J; Forsberg, Bertil; de Hoogh, Kees; Declerq, Christophe; Bono, Roberto; Piccioni, Pavilio; Quass, Ulrich; Heinrich, Joachim; Jarvis, Deborah; Pin, Isabelle; Beelen, Rob; Hoek, Gerard; Brunekreef, Bert; Schindler, Christian; Sunyer, Jordi; Krämer, Ursula; Kauffmann, Francine; Hansell, Anna L; Künzli, Nino; Probst-Hensch, Nicole

2015-01-01

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO₂, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 μg·m(-3) increase in NO₂ exposure was associated with lower levels of FEV₁ (-14.0 mL, 95% CI -25.8 to -2.1) and FVC (-14.9 mL, 95% CI -28.7 to -1.1). An increase of 10 μg·m(-3) in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV₁ (-44.6 mL, 95% CI -85.4 to -3.8) and FVC (-59.0 mL, 95% CI -112.3 to -5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe. Copyright ©ERS 2015.

Assessing the inter-observer variability of Computer-Aided Nodule Assessment and Risk Yield (CANARY) to characterize lung adenocarcinomas.

PubMed

Nakajima, Erica C; Frankland, Michael P; Johnson, Tucker F; Antic, Sanja L; Chen, Heidi; Chen, Sheau-Chiann; Karwoski, Ronald A; Walker, Ronald; Landman, Bennett A; Clay, Ryan D; Bartholmai, Brian J; Rajagopalan, Srinivasan; Peikert, Tobias; Massion, Pierre P; Maldonado, Fabien

2018-01-01

Lung adenocarcinoma (ADC), the most common lung cancer type, is recognized increasingly as a disease spectrum. To guide individualized patient care, a non-invasive means of distinguishing indolent from aggressive ADC subtypes is needed urgently. Computer-Aided Nodule Assessment and Risk Yield (CANARY) is a novel computed tomography (CT) tool that characterizes early ADCs by detecting nine distinct CT voxel classes, representing a spectrum of lepidic to invasive growth, within an ADC. CANARY characterization has been shown to correlate with ADC histology and patient outcomes. This study evaluated the inter-observer variability of CANARY analysis. Three novice observers segmented and analyzed independently 95 biopsy-confirmed lung ADCs from Vanderbilt University Medical Center/Nashville Veterans Administration Tennessee Valley Healthcare system (VUMC/TVHS) and the Mayo Clinic (Mayo). Inter-observer variability was measured using intra-class correlation coefficient (ICC). The average ICC for all CANARY classes was 0.828 (95% CI 0.76, 0.895) for the VUMC/TVHS cohort, and 0.852 (95% CI 0.804, 0.901) for the Mayo cohort. The most invasive voxel classes had the highest ICC values. To determine whether nodule size influenced inter-observer variability, an additional cohort of 49 sub-centimeter nodules from Mayo were also segmented by three observers, with similar ICC results. Our study demonstrates that CANARY ADC classification between novice CANARY users has an acceptably low degree of variability, and supports the further development of CANARY for clinical application.

Interpreting febrile neutropenia rates from randomized, controlled trials for consideration of primary prophylaxis in the real world: a systematic review and meta-analysis.

PubMed

Truong, J; Lee, E K; Trudeau, M E; Chan, K K W

2016-04-01

Guidelines recommend primary prophylaxis (PP) with granulocyte-colony-stimulating factors (G-CSF) for patients above a febrile neutropenia (FN) risk threshold of 20%. Practitioners often use FN rates of regimens based on data from randomized, controlled trials (RCTs), which are often comprised of highly selected patients. Patients in the community setting may be at higher risk of FN. A systematic literature search was conducted for full-length articles reporting FN rates for breast cancer-related chemotherapies between January 1996 and February 2014. A regimen was included if there was at least one RCT and one observational study. Meta-regression was used to model the odds of FN. 130 studies involving 29 regimens and 50 069 patients were identified. Sixty-five observational study (n = 7812) and 110 RCT (n = 42 257) cohorts were included. The unadjusted FN rate was 11.7% in observational and 7.9% in RCT cohorts. The univariable odds ratio (OR) for FN in the observational study compared with RCT cohorts was 1.58 [95% confidence interval (CI) 1.09-2.28; P = 0.017]. The FN rates remained significantly higher in the observational study compared with RCT cohorts (OR = 1.74; 95% CI 1.15-2.62; P = 0.012) after adjusting for age, chemotherapy intent, and regimen; this meant that a 13% (95% CI 8.7% to 17.9%) FN rate in RCT would translate into 20% FN rate in observational study. FN rates in the observational studies are significantly higher than suggested by RCTs. Guidelines should clarify how FN rates from RCTs should be applied in clinical practice. Large population-based studies are needed to confirm FN rates in the real world. © The Author 2015. 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.

Age-period-cohort analysis of tuberculosis notifications in Hong Kong from 1961 to 2005.

PubMed

Wu, P; Cowling, B J; Schooling, C M; Wong, I O L; Johnston, J M; Leung, C-C; Tam, C-M; Leung, G M

2008-04-01

Despite its wealth, excellent vital indices and robust health care infrastructure, Hong Kong has a relatively high incidence of tuberculosis (TB) (85.4 per 100 000). Hong Kong residents have also experienced a very rapid and recent epidemiological transition; the population largely originated from migration by southern Chinese in the mid 20th century. Given the potentially long latency period of TB infection, an investigation was undertaken to determine the extent to which TB incidence rates reflect the population history and the impact of public health interventions. An age-period-cohort model was used to break down the Hong Kong TB notification rates from 1961 to 2005 into the effects of age, calendar period and birth cohort. Analysis by age showed a consistent pattern across all the cohorts by year of birth, with a peak in the relative risk of TB at 20-24 years of age. Analysis by year of birth showed an increase in the relative risk of TB from 1880 to 1900, stable risk until 1910, then a linear rate of decline from 1910 with an inflection point at 1990 for a steeper rate of decline. Period effects yielded only one inflection during the calendar years 1971-5. Economic development, social change and the World Health Organisation's short-course directly observed therapy (DOTS) strategy have contributed to TB control in Hong Kong. The linear cohort effect until 1990 suggests that a relatively high, but slowly falling, incidence of TB in Hong Kong will continue into the next few decades.

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.

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/.

Association of lactase persistence genotype with milk consumption, obesity and blood pressure: a Mendelian randomization study in the 1982 Pelotas (Brazil) Birth Cohort, with a systematic review and meta-analysis.

PubMed

Hartwig, Fernando Pires; Horta, Bernardo Lessa; Smith, George Davey; de Mola, Christian Loret; Victora, Cesar Gomes

2016-10-01

Milk intake has been associated with lower blood pressure (BP) in observational studies, and randomized controlled trials suggested that milk-derived tripeptides have BP-lowering effects. Milk intake has also been associated with body mass index (BMI). Nevertheless, it is unclear whether increasing milk consumption would reduce BP in the general population. We investigated the association of milk intake with obesity and BP using genetically-defined lactase persistence (LP) based on the rs4988235 polymorphism in a Mendelian randomization design in the 1982 Pelotas (Southern Brazil) Birth Cohort. These results were combined with published reports identified through a systematic review using meta-analysis. In the 1982 Pelotas Birth Cohort, milk intake was 42 [95% confidence interval (CI): 18; 67) ml/day higher in LP individuals. In conventional observational analysis, each 1-dl/day increase in milk intake was associated with -0.26 (95% CI: -0.33; -0.19) kg/m 2 in BMI and -0.31 (95% CI: -0.46; -0.16) and -0.35 (95% CI: -0.46; -0.23) mmHg in systolic and diastolic BP, respectively. These results were not corroborated when analysing LP status, but confidence intervals were large. In random effects meta-analysis, LP individuals presented higher BMI [0.17 (95% CI: 0.07; 0.27) kg/m 2 ] and higher odds of overweight-obesity [1.09 (95% CI: 1.02; 1.17)]. There were no reliable associations for BP. Our study supports that LP is positively associated with obesity, suggesting that the negative association of milk intake with obesity is likely due to limitations of conventional observational studies. Our findings also do not support that increased milk intake leads to lower BP. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

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.

Assessing Health Professional Students' Cultural Competence Using a Global Perspective.

PubMed

Jones, Sophia; Pinto-Zipp, Genevieve

2017-01-01

The United States has become a diverse society, and healthcare professionals must view culture from a global perspective. The purpose of this study was to determine cultural competence levels of entering and exiting health science students within and across differing professional programs using the Global Worldview Cultural Competence Survey (GWCCS). 196 students participated in the study: 146 were entering students and 59 were exiting students. From the 146 entering students, 138 surveys were usable in the data analysis, and 58 of the 59 exiting were usable. Two separate cohorts of health professional students completed the GWCCS. Cohort 1 completed the GWCCS during the first 2 weeks of their academic program, and Cohort 2 completed the GWCCS in their final-year post-clinical experience. A significant difference in GWCCS total score was observed between entering and exiting students in health sciences, with the exiting students being more culturally competent. Although this study did not utilize a longitudinal study design, the findings demonstrate that the exiting cohort of health science students was more culturally competent than the entering cohort of health science students as determined by the GWCCS. However, neither cohort of students reached the level of proficiency.

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.

The role of birth cohorts in long-term trends in liver cirrhosis mortality across eight European countries.

PubMed

Trias-Llimós, Sergi; Bijlsma, Maarten J; Janssen, Fanny

2017-02-01

Understanding why inequalities in alcohol-related mortality trends by sex and country exist is essential for developing health policies. Birth cohort effects, indicative of differences by generation in drinking, have rarely been studied. This study estimated the relative contributions of birth cohorts to liver cirrhosis mortality trends and compared sex- and country-specific cohort patterns across eight European countries. Time-series analysis of population-level mortality data. Austria, Finland, Hungary, Italy, the Netherlands, Poland, Spain and Sweden; 1950-2011. National populations aged 15-94 years. We modelled country- and sex-specific liver cirrhosis mortality (from national vital registers) adjusting for age, period and birth cohort. Birth cohorts (adjusted for age and period) made statistically significant contributions to liver cirrhosis mortality in all countries and for both sexes (P < 0.001), and more so among women (average contribution to deviance reduction of 38.8%) than among men (17.4%). The observed cohort patterns were statistically different between all but two country pairs (P < 0.001). Sex differences existed overall (P < 0.001), but not in the majority of countries (P > 0.999). Visual inspection of birth cohort patterns reveals birth cohorts at higher risk of liver cirrhosis mortality. The inclusion of the birth cohort dimension improves the understanding of alcohol-attributable mortality trends in Europe. Birth cohorts at higher risk of liver cirrhosis mortality were born during 1935-49 in Sweden and Finland, around 1950 in Austria and the Netherlands and 1960 or later in Hungary, Italy, Poland and Spain. © 2016 Society for the Study of Addiction.

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

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

Comparison of HIV incidence estimated in clinical trial and observational cohort settings in a high risk fishing population in Uganda: Implications for sample size estimates.

PubMed

Abaasa, Andrew; Asiki, Gershim; Price, Matthew A; Ruzagira, Eugene; Kibengo, Freddie; Bahemuka, Ubaldo; Fast, Patricia E; Kamali, Anatoli

2016-04-04

Clinical trial participants may differ from the source population due to the demands of trial participation and self-selection, inadvertent selection of a lower-risk group, or both. We investigated the HIV risk status of volunteers in a Simulated Vaccine Efficacy Trial (SiVET) nested within a prospective observational cohort of fisher folks in South Western Uganda. Volunteers aged 18-49 years, at high risk for HIV from fishing communities in Masaka district were recruited into an observational cohort and followed quarterly. High risk was defined as a self-report, of at least one of the following in the past three months; sexually transmitted infections, unprotected sex with >1 partner or a new sexual partner, use of recreational drugs, weekly alcohol use, and/or frequent travel. Volunteers who had at least three months of follow-up in the observational cohort were consecutively enrolled in SiVET, administered Hepatitis B vaccine at months (0, 1, 6) and followed-up three days post vaccinations to mimic a vaccine trial schedule. HIV incidence over the next 12 months was compared between SiVET and the observational cohort studies. Between January 2012 and February 2013, 575 individuals were enrolled in the observational cohort, of whom 282 were enrolled in SiVET between July 2012 and February 2013. Despite similar pattern of reported risk behaviour in both studies, HIV incidence was higher in observational cohort, 11.4 cases/100 PYO [95% CI: 7.4-17.7] compared to 3.8 [95% CI: 2.0-7.0] in SiVET (p<0.01). SiVET volunteers tended to be men, having some education and longer-term residents, all factors that are also associated with lower HIV risk. We observed a lower HIV incidence in SiVET than in the observational cohort. The two populations differed significantly in demographics but not in reported risk. HIV incidence estimates from observational cohorts must be used with caution to estimate the trial study size. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impact of treatment with pioglitazone on stroke outcomes: a real world database analysis.

PubMed

Morgan, Christopher Ll; Inzucchi, Silvio E; Puelles, Jorge; Jenkins-Jones, Sara; Currie, Craig J

2018-05-07

Randomised controlled trials have reported an association between pioglitazone and reduced incidence of stroke in type 2 diabetic (T2DM) and insulin-resistant populations. We investigated this association within a real-world database. T2DM patients initiating pioglitazone between 2000-2012 were extracted from the Clinical Practice Research Datalink (CPRD); a UK routine. Two non-exposed control cohorts were matched on age, gender, HbA1c, diabetes duration, stroke history, co-morbidities and prior T2DM regimen. Control cohort-1 comprised patients initiating a new T2DM therapy as their respective case initiated pioglitazone. Control cohort-2 remained on the same T2DM regimen as their respective case prior to the case initiating pioglitazone. The primary outcome was incident stroke; other outcomes included mortality, hospital length of stay and stroke recurrence. 4,234 pioglitazone patients matched to controls in cohort-1 and 3,604 in cohort-2. For the primary outcome there were significantly reduced hazard ratios (HRs) for cases:controls. Cohort 1, the HR was 0.627 (95% CI, 0.404-0.972) during the therapy period and 0.640 (0.485-0.843) over the entire observation period; respective HRs were 0.516 (0.336-0.794) and 0.773 (0.611-0.978) for cohort 2. There was no significant difference in 30-day mortality rate or rate of recurrent stroke. For hospitalised stroke events there was a significant difference in length of stay for patients discharged to usual residence (median 3.0 days versus 7.0 days; p=0.008) for control cohort-2 whilst on-treatment. In support of evidence from two large randomized trials, these observational data show that pioglitazone has a potent effect in reducing stroke events in patients with type 2 diabetes. This article is protected by copyright. All rights reserved.

Matched cohort comparison of endovascular abdominal aortic aneurysm repair with and without EndoAnchors.

PubMed

Muhs, Bart E; Jordan, William; Ouriel, Kenneth; Rajaee, Sareh; de Vries, Jean-Paul

2018-06-01

The objective of this study was to examine whether prophylactic use of EndoAnchors (Medtronic, Santa Rosa, Calif) contributes to improved outcomes after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms through 2 years. The Aneurysm Treatment Using the Heli-FX Aortic Securement System Global Registry (ANCHOR) subjects who received prophylactic EndoAnchors during EVAR were considered for this analysis. Imaging data of retrospective subjects who underwent EVAR at ANCHOR enrolling institutions were obtained to create a control sample. Nineteen baseline anatomic measurements were used to perform propensity score matching, yielding 99 matched pairs. Follow-up imaging of the ANCHOR and control cohorts was then compared to examine outcomes through 2 years, using Kaplan-Meier survival analysis. Freedom from type Ia endoleak was 97.0% ± 2.1% in the ANCHOR cohort and 94.1% ± 2.5% in the control cohort through 2 years (P = .34). The 2-year freedom from neck dilation in the ANCHOR and control cohorts was 90.4% ± 5.6% and 87.3% ± 4.3%, respectively (P = .46); 2-year freedom from sac enlargement was 97.0% ± 2.1% and 94.0% ± 3.0%, respectively (P = .67). No device migration was observed. Aneurysm sac regression was observed in 81.1% ± 9.5% of ANCHOR subjects through 2 years compared with 48.7% ± 5.9% of control subjects (P = .01). Cox regression analysis found an inverse correlation between number of hostile neck criteria met and later sac regression (P = .05). Preoperative neck thrombus circumference and infrarenal diameter were also variables associated with later sac regression, although not to a significant degree (P = .10 and P = .06, respectively). Control subjects with thrombus were significantly less likely to experience later sac regression than those without thrombus (6% and 43%, respectively; P = .001). In ANCHOR subjects, rate of regression was not significantly different in subjects with or without thrombus (33% and 36%, respectively; P = .82). Control subjects with wide aortic necks (>28 mm) were observed to experience sac regression at a lower rate than subjects with smaller diameter necks (10% and 44%, respectively; P = .004). Wide neck and normal neck subjects implanted with EndoAnchors experienced later sac regression at roughly equivalent rates (44% and 33%, respectively; P = .50). In propensity-matched cohorts of subjects undergoing EVAR, the rate of sac regression in subjects treated with EndoAnchors was significantly higher. EndoAnchors may mitigate the adverse effect of wide infrarenal necks and neck thrombus on sac regression, although further studies are needed to evaluate the long-term effect of EndoAnchors. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Personal hair dyes use and risk of glioma: a meta-analysis

PubMed Central

Shao, Chuan; Qi, Zhen-Yu; Hui, Guo-Zhen; Wang, Zhong

2013-01-01

Background and Objective: Use of hair dyes for glioma risk has been investigated in numerous epidemiological studies, but the evidence is inconsistent. Therefore, a meta-analysis was performed to estimate the association between hair dyes use and glioma risk. Methods: We searched PubMed and EMBASE databases without any limitations, covering all papers published by the end of March 8, 2013. Cohort and case-control studies reporting relative risk estimates (RRs) with corresponding 95% confidence intervals (CIs) (or data to calculate them) on this issue were included. Random effects models were used to calculate the pooled RRs and corresponding 95% CIs. Results: Four case-control and two cohort studies were included in this meta-analysis. The summary RRs and 95 % CIs for ever users of any hair dyes were 1.132 (0.887-1.446) for all studies, 1.291 (0.938-1.777) for case-control studies, and 0.903 (0.774-1.054) for cohort studies. In the subgroup analysis by geographic regions and sex, the similar results were detected. No significant associations were also observed among the studies which reported data involving permanent hair dye use and duration of any hair dye use. Conclusion: In summary, the results of our study demonstrated that hair dyes use is not associated with risk of glioma. PMID:24179568

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.

Impact of Exercise Counseling on Physical Function in Chronic Kidney Disease: An Observational Study.

PubMed

Bohm, Clara J; Storsley, Leroy J; Hiebert, Brett M; Nelko, Serena; Tangri, Navdeep; Cheskin, Lawrence J; McAdams-DeMarco, Mara A; Rigatto, Claudio

2018-01-01

Individuals with chronic kidney disease (CKD) have low levels of physical activity and physical function. Although guidelines endorse exercise counseling for individuals with CKD, it is not yet part of routine care. We investigated the effect of attending a real-life exercise counseling clinic (ECC) on physical function in individuals with CKD. Retrospective analysis of prospectively collected observational data with quasi-experimental design. Patients with all stages of CKD registered in a large provincial renal program were eligible. The exposed cohort who attended the ECC between January 1, 2011, and March 15, 2014, included 214 individuals. The control cohort included 292 individuals enrolled in an observational study investigating longitudinal change in frailty during the same time period. Attendance at an ECC. Change in physical function as measured by Short Physical Performance Battery (SPPB) score, physical activity level (Human Activity Profile [HAP]/Physical Activity Scale for the Elderly [PASE]), and health-related quality of life (HRQOL; EQ5D/VAS) over 1 year. Eighty-seven individuals in the ECC cohort and 125 participants in the control cohort completed 1-year follow-up. Baseline median SPPB score was 10 (interquartile range [IQR]: 9-12) and 9 (IQR: 7-11) in the ECC and control cohorts, respectively ( P < .01). At 1 year, SPPB scores were 10 (IQR: 8-12) and 9 (IQR: 6-11) in the ECC and control cohorts, respectively ( P = .04). Mean change in SPPB over 1 year was not significantly different between groups: -0.33 (95% confidence interval [CI]: -0.81 to 0.15) in ECC and -0.22 (95% CI: -0.61 to 0.17) in control ( P = .72). There was no significant difference in the proportion of individuals in each cohort with an increase/decrease in SPPB score over time. There was no significant change in physical activity or HRQOL over time between groups. Quasi-experimental design, low rate of follow-up attendance. In this pragmatic study, exercise counseling had no significant effect on change in SPPB score, suggesting that a single exercise counseling session alone is inadequate to improve physical function in CKD.

Inverse Demographic Analysis of Compensatory Responses to Resource Limitation in the Mysid Crustacean Americamysis bahia

EPA Science Inventory

Most observations of stressor effects on marine crustaceans are made on individuals or even-aged cohorts. Results of these studies are difficult to translate into ecological predictions, either because life cycle models are incomplete, or because stressor effects on mixed age po...

Human Endogenous Retrovirus HERV-Fc1 Association with Multiple Sclerosis Susceptibility: A Meta-Analysis

PubMed Central

García-Montojo, Marta; Alcina, Antonio; Fedetz, María; Alloza, Iraide; Astobiza, Ianire; Leyva, Laura; Fernández, Oscar; Izquierdo, Guillermo; Antigüedad, Alfredo; Arroyo, Rafael; Álvarez-Lafuente, Roberto; Vandenbroeck, Koen; Matesanz, Fuencisla; Urcelay, Elena

2014-01-01

Background Human endogenous retroviruses (HERVs) are repetitive sequences derived from ancestral germ-line infections by exogenous retroviruses and different HERV families have been integrated in the genome. HERV-Fc1 in chromosome X has been previously associated with multiple sclerosis (MS) in Northern European populations. Additionally, HERV-Fc1 RNA levels of expression have been found increased in plasma of MS patients with active disease. Considering the North-South latitude gradient in MS prevalence, we aimed to evaluate the role of HERV-Fc1on MS risk in three independent Spanish cohorts. Methods A single nucleotide polymorphism near HERV-Fc1, rs391745, was genotyped by Taqman chemistry in a total of 2473 MS patients and 3031 ethnically matched controls, consecutively recruited from: Northern (569 patients and 980 controls), Central (883 patients and 692 controls) and Southern (1021 patients and 1359 controls) Spain. Our results were pooled in a meta-analysis with previously published data. Results Significant associations of the HERV-Fc1 polymorphism with MS were observed in two Spanish cohorts and the combined meta-analysis with previous data yielded a significant association [rs391745 C-allele carriers: pM-H = 0.0005; ORM-H (95% CI) = 1.27 (1.11–1.45)]. Concordantly to previous findings, when the analysis was restricted to relapsing remitting and secondary progressive MS samples, a slight enhancement in the strength of the association was observed [pM-H = 0.0003, ORM-H (95% CI) = 1.32 (1.14–1.53)]. Conclusion Association of the HERV-Fc1 polymorphism rs391745 with bout-onset MS susceptibility was confirmed in Southern European cohorts. PMID:24594754

Dietary Fiber and Metabolic Syndrome: A Meta-Analysis and Review of Related Mechanisms

PubMed Central

Chen, Guo-Chong; Wang, Xiao-Ping; Qin, Liqiang

2017-01-01

(1) Background: Dietary fiber intake may provide beneficial effects on the components of metabolic syndrome (MetS); however, observational studies reported inconsistent results for the relationship between dietary fiber intake and MetS risk. We conducted a meta-analysis to quantify previous observational studies and a narrative review to summarize mechanisms involved in the potential relationship. (2) Methods: The literature was searched on PubMed and Web of Science until 28 November 2017. A random-effects model was used to calculate the summary risk estimates. Eleven cross-sectional studies and three cohort studies were included in the meta-analysis. Results from the original studies were reported as odds ratios (ORs) or relative ratios (RRs) of the MetS associated with different levels of dietary fiber intake, and the ORs/RRs comparing the highest with lowest categories of the intake were pooled. (3) Results: For the cross-sectional studies, the pooled OR was 0.70 (95% confidence interval (CI): 0.61–0.82) with evidence of high heterogeneity (I2 = 74.4%, p < 0.001) and publication bias (p for Egger’s test < 0.001). After removing four studies, results remained significant (OR = 0.67, 95% CI: 0.58–0.78) and the heterogeneity was largely reduced (I2 = 32.4%, p = 0.181). For the cohort studies, the pooled RR was 0.86 (95% CI: 0.70–1.06). (4) Conclusion: Although the meta-analysis suggests an inverse association between dietary fiber intake and risk of MetS, and the association was supported by a wide range of mechanism studies, the findings are limited by insufficient cohort data. More prospective studies are needed to further verify the association between dietary fiber intake and the risk of MetS. PMID:29278406

Relapse after withdrawal from anti-TNF therapy for inflammatory bowel disease: an observational study, plus systematic review and meta-analysis.

PubMed

Kennedy, N A; Warner, B; Johnston, E L; Flanders, L; Hendy, P; Ding, N S; Harris, R; Fadra, A S; Basquill, C; Lamb, C A; Cameron, F L; Murray, C D; Parkes, M; Gooding, I; Ahmad, T; Gaya, D R; Mann, S; Lindsay, J O; Gordon, J; Satsangi, J; Hart, A; McCartney, S; Irving, P; Lees, C W

2016-04-01

Infliximab and adalimumab have established roles in inflammatory bowel disease (IBD) therapy. UK regulators mandate reassessment after 12 months' anti-TNF therapy for IBD, with consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation. To establish outcomes following anti-TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta-analysis. A retrospective observational study was performed on 166 patients with IBD (146 with Crohn's disease (CD) and 20 with ulcerative colitis [UC) and IBD unclassified (IBDU)] withdrawn from anti-TNF for sustained remission. Meta-analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD, 122 UC). Relapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD, and 42% by 1 year and 47% by 2 years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis [hazard ratio (HR) 2.78 for age <22 years], white cell count (HR 3.22 for >5.25 × 10 9 /L) and faecal calprotectin (HR 2.95 for >50 μg/g) at drug withdrawal. Neither continued immunomodulators nor endoscopic remission were predictors. In the meta-analysis, estimated 1-year relapse rates were 39% and 35% for CD and UC/IBDU respectively. Retreatment with anti-TNF was successful in 88% for CD and 76% UC/IBDU. Assimilation of all available data reveals remarkable homogeneity. Approximately one-third of patients with IBD flare within 12 months of withdrawal of anti-TNF therapy for sustained remission. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Green tea and liver cancer risk: A meta-analysis of prospective cohort studies in Asian populations.

PubMed

Huang, Ya-Qing; Lu, Xin; Min, Han; Wu, Qian-Qian; Shi, Xiao-Ting; Bian, Kang-Qi; Zou, Xiao-Ping

2016-01-01

The aim of this meta-analysis was to investigate whether an association existed between green tea consumption and the risk for liver cancer in prospective cohort studies in Asian populations. Relevant studies were identified by searching PubMed, EMBASE, ISI Web of Science, and the Chinese Bio-medicine Database published before April 2015. Study-specific risk estimates for the highest versus non- or lowest and increment of daily cup of green tea consumption levels were combined based on fixed- or random-effects models. STATA 11.0 (Stata Corporation, College Station, TX, USA) software was used for statistical analysis. Nine prospective cohort articles involving 465,274 participants and 3694 cases of liver cancer from China, Japan, and Singapore were included. The summary relative risk (RR) indicated a significant association between the highest green tea consumption and reduced risk for liver cancer (summary RR, 0.88; 95% confidence interval [CI], 0.81-0.97). However, no statistically significant association was observed when analyzing daily consumption of one cup (summary RR, 0.97; 95% CI, 0.95-1.00). When stratified by sex, the protective effect of green tea consumption on risk for liver cancer was observed only in the group of women (summary RR, 0.78; 95% CI, 0.64-0.96), but not in men (summary RR, 0.89; 95% CI, 0.79-1.00). The present analysis indicated the preventive effects of green tea intake on the risk for liver cancer in female Asian populations. However, additional studies are needed to make a convincing case for this association. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluating the Impact of Database Heterogeneity on Observational Study Results

PubMed Central

Madigan, David; Ryan, Patrick B.; Schuemie, Martijn; Stang, Paul E.; Overhage, J. Marc; Hartzema, Abraham G.; Suchard, Marc A.; DuMouchel, William; Berlin, Jesse A.

2013-01-01

Clinical studies that use observational databases to evaluate the effects of medical products have become commonplace. Such studies begin by selecting a particular database, a decision that published papers invariably report but do not discuss. Studies of the same issue in different databases, however, can and do generate different results, sometimes with strikingly different clinical implications. In this paper, we systematically study heterogeneity among databases, holding other study methods constant, by exploring relative risk estimates for 53 drug-outcome pairs and 2 widely used study designs (cohort studies and self-controlled case series) across 10 observational databases. When holding the study design constant, our analysis shows that estimated relative risks range from a statistically significant decreased risk to a statistically significant increased risk in 11 of 53 (21%) of drug-outcome pairs that use a cohort design and 19 of 53 (36%) of drug-outcome pairs that use a self-controlled case series design. This exceeds the proportion of pairs that were consistent across databases in both direction and statistical significance, which was 9 of 53 (17%) for cohort studies and 5 of 53 (9%) for self-controlled case series. Our findings show that clinical studies that use observational databases can be sensitive to the choice of database. More attention is needed to consider how the choice of data source may be affecting results. PMID:23648805

Trends in Lung Cancer Incidence in Delhi, India 1988-2012: Age-Period-Cohort and Joinpoint Analyses

PubMed

Malhotra, Rajeev Kumar; Manoharan, Nalliah; Nair, Omana; Deo, Suryanarayana; Rath, Goura Kishor

2018-06-25

Introduction: Lung cancer (LC) has been one of the most commonly diagnosed cancers worldwide, both in terms of new cases and mortality. Exponential growth of economic and industrial activities in recent decades in the Delhi urban area may have increased the incidence of LC. The primary objective of this study was to evaluate the time trend according to gender. Method: LC incidence data over 25 years were obtained from the population based urban Delhi cancer registry. Joinpoint regression analysis was applied for evaluating the time trend of age-standardized incidence rates. The age-period-cohort (APC) model was employed using Poisson distribution with a log link function and the intrinsic estimator method. Results: During the 25 years, 13,489 male and 3,259 female LC cases were registered, accounting for 9.78% of male and 2.53% of female total cancer cases. Joinpoint regression analysis revealed that LC incidence in males continued to increase during the entire period, a sharp acceleration being observed starting from 2009. In females the LC incidence rate remained a plateau during 1988-2002 and thereafter increased. The cumulative risks for 1988-2012 were 1.79% and 0.45%. The full APC (IE) model showed best fit for an age-period-cohort effect on LC incidence, with significant increase with age peaking at 70-74 years in males and 65-69 years in females. A rising period effect was observed after adjusting for age and cohort effects in both genders and a declining cohort effect was identified after controlling for age and period effects. Conclusion: The incidence of LC in urban Delhi showed increasing trend from 1988-2012. Known factors such as environmental conservation, tobacco control, physical activity awareness and medical security should be implemented more vigorously over the long term in our population. Creative Commons Attribution License

Homicides among women in the different Brazilian regions in the last 35 years: an analysis of age-period-birth cohort effects.

PubMed

Souza, Edinilsa Ramos de; Meira, Karina Cardoso; Ribeiro, Adalgisa Peixoto; Santos, Juliano Dos; Guimarães, Raphael Mendonça; Borges, Laiane Felix; Oliveira, Lannuzya Veríssimo E; Simões, Taynãna César

2017-09-01

The aim of this study is to estimate the effects of age-period-birth cohort (APC) on female homicides. This is an ecological study which analyzed the violence-related death records of women aged 10 years and older, in the Brazilian geographic regions, between 1980 and 2014. Data on mortality were extracted from the Mortality Information System. The trend analysis was conducted using negative binomial regression and APC effects were analyzed using estimable functions. The average mortality rate for the period was 5.13 deaths per 100,000 women, with the highest rates observed in the Central-West (7.98 deaths), followed by the Southeast (4.78 deaths), North (4.77 deaths), Northeast (4.05 deaths) and South (3.82 deaths) regions. All regions presented a decrease in the risk of death in the period from 2010 to 2014, except for the Northeast region (RR = 1.06, 95% CI 1.02 to 1.10). There was a progressive increase in the homicide risk for women born from 1955 to 1959 in all Brazilian regions. Younger women are at higher risk of dying from homicides in all Brazilian geographic regions. The upward trend of homicide mortality rates according to birth cohort was significant and the highest risk was observed in women born between 2000 and 2004.

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.

Efficient Bayesian mixed model analysis increases association power in large cohorts

PubMed Central

Loh, Po-Ru; Tucker, George; Bulik-Sullivan, Brendan K; Vilhjálmsson, Bjarni J; Finucane, Hilary K; Salem, Rany M; Chasman, Daniel I; Ridker, Paul M; Neale, Benjamin M; Berger, Bonnie; Patterson, Nick; Price, Alkes L

2014-01-01

Linear mixed models are a powerful statistical tool for identifying genetic associations and avoiding confounding. However, existing methods are computationally intractable in large cohorts, and may not optimize power. All existing methods require time cost O(MN2) (where N = #samples and M = #SNPs) and implicitly assume an infinitesimal genetic architecture in which effect sizes are normally distributed, which can limit power. Here, we present a far more efficient mixed model association method, BOLT-LMM, which requires only a small number of O(MN)-time iterations and increases power by modeling more realistic, non-infinitesimal genetic architectures via a Bayesian mixture prior on marker effect sizes. We applied BOLT-LMM to nine quantitative traits in 23,294 samples from the Women’s Genome Health Study (WGHS) and observed significant increases in power, consistent with simulations. Theory and simulations show that the boost in power increases with cohort size, making BOLT-LMM appealing for GWAS in large cohorts. PMID:25642633

Feasibility and utility of applications of the common data model to multiple, disparate observational health databases.

PubMed

Voss, Erica A; Makadia, Rupa; Matcho, Amy; Ma, Qianli; Knoll, Chris; Schuemie, Martijn; DeFalco, Frank J; Londhe, Ajit; Zhu, Vivienne; Ryan, Patrick B

2015-05-01

To evaluate the utility of applying the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) across multiple observational databases within an organization and to apply standardized analytics tools for conducting observational research. Six deidentified patient-level datasets were transformed to the OMOP CDM. We evaluated the extent of information loss that occurred through the standardization process. We developed a standardized analytic tool to replicate the cohort construction process from a published epidemiology protocol and applied the analysis to all 6 databases to assess time-to-execution and comparability of results. Transformation to the CDM resulted in minimal information loss across all 6 databases. Patients and observations excluded were due to identified data quality issues in the source system, 96% to 99% of condition records and 90% to 99% of drug records were successfully mapped into the CDM using the standard vocabulary. The full cohort replication and descriptive baseline summary was executed for 2 cohorts in 6 databases in less than 1 hour. The standardization process improved data quality, increased efficiency, and facilitated cross-database comparisons to support a more systematic approach to observational research. Comparisons across data sources showed consistency in the impact of inclusion criteria, using the protocol and identified differences in patient characteristics and coding practices across databases. Standardizing data structure (through a CDM), content (through a standard vocabulary with source code mappings), and analytics can enable an institution to apply a network-based approach to observational research across multiple, disparate observational health databases. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.

Neurodevelopment in preterm infants with and without placenta-related intrauterine growth restriction and its relation to perinatal and postnatal factors.

PubMed

Candel-Pau, Júlia; Perapoch López, Josep; Castillo Salinas, Félix; Sánchez Garcia, Olga; Pérez Hoyos, Santiago; Llurba Olivé, Elisa

2016-01-01

Intrauterine-growth restriction is associated with impaired neurodevelopment. However, studies on early childhood neurodevelopment of premature infants with placenta-related intrauterine-growth restriction (IUGR) are scarce and heterogeneous. We aimed to analyze the impact of placenta-related IUGR on preschool age neurodevelopment in preterm infants, and to ascertain which prenatal and postnatal factors influence neurodevelopment in these infants. Prospective cohorts study: 48 placenta-related IUGR premature infants and 25 matched non-IUGR premature infants (mean gestational age: 31.4 and 31.6 weeks, respectively). Preschool neurodevelopment assessment with cognitive Bayley Scales III and with ASQ-III surveys (age interval: 34.07-42.50 months). Inter-cohort result comparison. Analysis of perinatal and environmental factors associated with impaired neurodevelopment in both cohorts. No statistically significant neurodevelopment differences were observed at preschool age between both preterm cohorts. Multivariate analysis of perinatal and environmental factors showed daycare, breastfeeding, higher parental educational level, and absence of severe neonatal morbidity to be associated with a lower risk of altered neurodevelopment at preschool age. Placenta-related IUGR does not have a significant impact on preschool neurodevelopment in our preterm patients. Instead, post-natal positive environmental factors such as parental educational level, breastfeeding, and daycare attendance make a difference towards an improvement in neurodevelopment in these infants.

Postnatal Growth Patterns in a Chilean Cohort: The Role of SES and Family Environment

PubMed Central

Kang Sim, D. E.; Cappiello, M.; Castillo, M.; Lozoff, B.; Martinez, S.; Blanco, E.; Gahagan, S.

2012-01-01

Objective. This study examined how family environmental characteristics served as mediators in the relationship between socioeconomic conditions and infant growth in a cohort of Chilean infants. Methods. We studied 999 infants, born between 1991 and 1996, from a longitudinal cohort which began as an iron deficiency anemia preventive trial. SES (Graffar Index), the Life Experiences Survey, and the Home Observation for Measurement of the Environment (HOME) were assessed in infancy. Using path analysis, we assessed the relationships between the social factors, home environment, and infant growth. Results. During the first year, weight and length gain averaged 540 grams/month and 6.5 cm/month, respectively. In the path analysis model for weight gain, higher SES and a better physical environment were positively related to higher maternal warmth, which in turn was associated with higher average weight gain. Higher SES was directly related to higher average length gain. Conclusions. In our cohort, a direct relationship between SES and length gain developed during infancy. Higher SES was indirectly related to infant weight gain through the home environment and maternal warmth. As the fastest growing infants are at risk for later obesity, new strategies are needed to encourage optimal rather than maximal growth. PMID:22666275

Intrauterine temperature during intrapartum amnioinfusion: a prospective observational study.

PubMed

Tomlinson, T M; Schaecher, C; Sadovsky, Y; Gross, G

2012-07-01

To determine the influence of routine intrapartum amnioinfusion (AI) on intrauterine temperature. Prospective observational study. Maternity unit, Barnes Jewish Hospital, St Louis, MO, USA. Forty women with singleton gestations and an indication for intrapartum intrauterine pressure catheter placement. Using a temperature probe, we digitally recorded intrauterine temperature every 10 minutes during labour. Amnioinfusion was administered according to a standard protocol using saline equilibrated to the ambient temperature. Mean intrauterine temperature during labour. Participants were monitored for a mean of 280 minutes (range 20-820). A total of 164 intrauterine temperature readings in the AI cohort were compared with 797 control measurements. When compared with controls, we observed a lower intrauterine temperature in the AI cohort (36.4 versus 37.4°C, P<0.01). More measurements in the AI cohort were recorded in the presence of intrapartum fever (40% versus 30%). A subgroup analysis of measurements recorded in afebrile parturients revealed an even greater effect of AI (1.5°C decrease, 37.3 versus 35.8°C, P<0.01). Routine intrapartum AI using saline equilibrated to a mean ambient temperature of 25.0°C reduces intrauterine temperature and may thereby affect fetal core temperature. © 2012 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2012 RCOG.

Coffee Drinking and the Risk of Endometrial Cancer: An Updated Meta-Analysis of Observational Studies.

PubMed

Lukic, Marko; Guha, Neela; Licaj, Idlir; van den Brandt, Piet A; Stayner, Leslie Thomas; Tavani, Alessandra; Weiderpass, Elisabete

2018-01-01

Several compounds contained in coffee have been found to suppress carcinogenesis in experimental studies. We conducted a dose-response meta-analysis to assess the impact of coffee consumption on the risk of endometrial cancer. We searched MEDLINE and EMBASE databases for studies published up to August 2016. Using random effects models, we estimated summary relative risks (RR) for cohort studies and odds ratios (OR) for case-control studies with 95% confidence intervals (CI). Dose-response analyses were conducted by using generalized least square trend estimation. We identified 12 cohort studies and 8 case-control studies eligible for inclusion, contributing with 11,663 and 2,746 endometrial cancer cases, respectively. The summary RR for highest compared with lowest coffee intake was 0.74 (95% CI: 0.68-0.81; p heterogeneity = 0.09, I 2 = 32%). The corresponding summary RR among cohort studies was 0.78 (95% CI: 0.71-0.85; p heterogeneity = 0.14, I 2 = 31.9%) and 0.63 (95% CI: 0.53-0.76; p heterogeneity = 0.57, I 2 = 0%) for case-control studies. One-cup increment per day was associated with 3% risk reduction (95% CI: 2-4%) in cohort studies and 12% (95% CI: 5-18%) in case-control studies. After pooling the results from 5 cohort studies, the association remained significant only in women with body mass index over 30 (RR = 0.71, 95% CI: 0.61-0.81). The results from our meta-analysis strengthen the evidence of a protective effect of coffee consumption on the risk of EC and further suggest that increased coffee intake might be particularly beneficial for women with obesity.

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.

Predictive Accuracy of the Veterans Aging Cohort Study (VACS) Index for Mortality with HIV Infection: A North American Cross Cohort Analysis

PubMed Central

Justice, AC; Modur, S; Tate, JP; Althoff, KN; Jacobson, LP; Gebo, K; Kitahata, M; Horberg, M; Brooks, J; Buchacz, K; Rourke, SB; Rachlis, A; Napravnik, S; Eron, J; Willig, H; Moore, R; Kirk, GD; Bosch, R; Rodriguez, B; Hogg, RS; Thorne, J; Goedert, JJ; Klein, M; Gill, MJ; Deeks, S; Sterling, TR; Anastos, K; Gange, SJ

2013-01-01

Background By supplementing an index composed of HIV biomarkers and age (Restricted Index) with measures of organ injury, the Veterans Aging Cohort Study (VACS) Index more completely reflects risk of mortality. We compare the accuracy of the VACS and Restricted Indices 1) among subjects outside the Veterans Healthcare System (VA), 2) over 1–5 years of prior exposure to antiretroviral therapy (ART), and 3) within important patient subgroups. Methods We used data from 13 cohorts in the North American AIDS Cohort Collaboration (NA-ACCORD, n=10, 835) limiting analyses to HIV-infected subjects with at least 12 months exposure to ART. Variables included demographic, laboratory (CD4 count, HIV-1 RNA, hemoglobin, platelets, aspartate and alanine transaminase, creatinine and hepatitis C status), and survival. We used C statistic and net reclassification improvement (NRI) to test discrimination varying prior ART exposure from 1–5 years. We then combined VA (n=5,066) and NA-ACCORD data, fit a parametric survival model, and compared predicted to observed mortality by cohort, gender, age, race, and HIV-1 RNA level. Results Mean follow-up was 3.3 years (655 deaths). Compared with the Restricted Index, the VACS Index showed greater discrimination (C statistic: 0.77 vs. 0.74; NRI 12%; p<0.0001). NRI was highest among those with HIV-1 RNA<500 copies/ml (25%) and age ≥50 years (20%). Predictions were similar to observed mortality among all subgroups. Conclusion VACS Index scores discriminate risk and translate into accurate mortality estimates over 1–5 years of exposures to ART and for diverse patient subgroups from North American PMID:23187941

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

Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis

PubMed Central

Adam, Martin; Schikowski, Tamara; Carsin, Anne Elie; Cai, Yutong; Jacquemin, Benedicte; Sanchez, Margaux; Vierkötter, Andrea; Marcon, Alessandro; Keidel, Dirk; Sugiri, Dorothee; Al Kanani, Zaina; Nadif, Rachel; Siroux, Valérie; Hardy, Rebecca; Kuh, Diana; Rochat, Thierry; Bridevaux, Pierre-Olivier; Eeftens, Marloes; Tsai, Ming-Yi; Villani, Simona; Phuleria, Harish Chandra; Birk, Matthias; Cyrys, Josef; Cirach, Marta; de Nazelle, Audrey; Nieuwenhuijsen, Mark J.; Forsberg, Bertil; de Hoogh, Kees; Declerq, Christophe; Bono, Roberto; Piccioni, Pavilio; Quass, Ulrich; Heinrich, Joachim; Jarvis, Deborah; Pin, Isabelle; Beelen, Rob; Hoek, Gerard; Brunekreef, Bert; Schindler, Christian; Sunyer, Jordi; Krämer, Ursula; Kauffmann, Francine; Hansell, Anna L.; Künzli, Nino; Probst-Hensch, Nicole

2015-01-01

The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO2, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 μg·m−3 increase in NO2 exposure was associated with lower levels of FEV1 (−14.0 mL, 95% CI −25.8 to −2.1) and FVC (−14.9 mL, 95% CI −28.7 to −1.1). An increase of 10 μg·m−3 in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV1 (−44.6 mL, 95% CI −85.4 to −3.8) and FVC (−59.0 mL, 95% CI −112.3 to −5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe. PMID:25193994

Examining lung cancer risks across different industries and occupations in Ontario, Canada: the establishment of the Occupational Disease Surveillance System.

PubMed

Jung, James K H; Feinstein, Saul G; Palma Lazgare, Luis; Macleod, Jill S; Arrandale, Victoria H; McLeod, Christopher B; Peter, Alice; Demers, Paul A

2018-05-07

The Occupational Disease Surveillance System (ODSS) was established in Ontario, Canada by linking a cohort of workers with data created from Workplace Safety and Insurance Board (WSIB) claims to administrative health databases. The aim of this study was to use ODSS to identify high-risk industry and occupation groups for lung cancer in Ontario. Workers in the WSIB lost time claims database were linked to the Ontario Cancer Registry using subjects' health insurance numbers, name, sex, birthdate and death date (if applicable). Several occupations and industries known to be at increased risk were outlined a priori to examine whether ODSS could replicate these associations. Age-adjusted, sex-stratified Cox proportional hazard models compared the risk of lung cancer within one industry/occupation versus all other groups in the cohort. Workers with a lung cancer diagnosis prior to cohort entry were excluded for analysis, leaving 2 187 762 workers for analysis. During the 1983 to 2014 follow-up, 34 661 workers in the cohort were diagnosed with lung cancer. Among expected high-risk industries, elevated risks were observed among workers in quarries/sand pits and construction industries for both sexes, and among males in metal mines, iron foundries, non-metallic mineral products industries and transportation industries. Excess risk was also observed among occupations in drilling/blasting, other mining/quarrying, mineral ore treating, excavating/grading/paving, truck driving, painting, bus driving and construction. This current surveillance system identified several established high-risk groups for lung cancer and could be used for ongoing surveillance of occupational lung cancer in Ontario. © 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.

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.

Social change and birth cohort increase in loneliness among Chinese older adults: a cross-temporal meta-analysis, 1995-2011.

PubMed

Yan, Zhimin; Yang, Xun; Wang, Lei; Zhao, Yuhan; Yu, Lin

2014-11-01

In China, rapid economic growth and increasing social problems constitute the two basic characteristics underlying contemporary social change. With dramatic social change, loneliness in older adults may have changed across birth cohorts, thus altering older adults' mental health. The present study aims to identify birth cohort changes in Chinese older adults' loneliness and the social indicators underlying these changes. Cross-temporal meta-analysis was utilized to investigate changes in Chinese older adults' loneliness from 1995 to 2011. We analyzed 25 studies (N = 13,280 adults; age ≥ 60 years) employing the University of California at Los Angeles Loneliness Scale. We correlated loneliness scores with social indicators and matched these correlations for three periods: ten years before the data collection, five years before data collection, and during the year of data collection. Loneliness levels in Chinese older adults have increased by 1.02 standard deviations from 1995 to 2011. Social indicators such as increased urbanization level, personal medical expenditure, divorce rate, the Gini coefficient, and unemployment rate significantly predicted loneliness in Chinese older adults. Decrease in social connectedness and increase in levels of health threat may be responsible for the observed increase in levels of loneliness. Cross-temporal meta-analysis revealed a birth cohort increase in loneliness among Chinese older adults. We conclude that changes in social connectedness and levels of health threat likely play an important role in predicting loneliness in the population of Chinese elderly adults.

Personality traits in old age: measurement and rank-order stability and some mean-level change.

PubMed

Mõttus, René; Johnson, Wendy; Deary, Ian J

2012-03-01

Lothian Birth Cohorts, 1936 and 1921 were used to study the longitudinal comparability of Five-Factor Model (McCrae & John, 1992) personality traits from ages 69 to 72 years and from ages 81 to 87 years, and cross-cohort comparability between ages 69 and 81 years. Personality was measured using the 50-item International Personality Item Pool (Goldberg, 1999). Satisfactory measurement invariance was established across time and cohorts. High rank-order stability was observed in both cohorts. Almost no mean-level change was observed in the younger cohort, whereas Extraversion, Agreeableness, Conscientiousness, and Intellect declined significantly in the older cohort. The older cohort scored higher on Agreeableness and Conscientiousness. In these cohorts, individual differences in personality traits continued to be stable even in very old age, mean-level changes accelerated.

Onto, up, off the Academic Faculty Ladder: The Gendered Effects of Family on Career Transitions for a Cohort of Social Science Ph.D.s

ERIC Educational Resources Information Center

Morrison, Emory; Rudd, Elizabeth; Nerad, Maresi

2011-01-01

With event history analysis, we examine the impact of gender, marital status and spouse type, and parenting at key transition points in the early careers of more than 2,000 social science Ph.D. graduates. This analysis (a) uses data from recent Ph.D. graduates; (b) disentangles the effects of marriage and parenting; and (c) observes the effects of…

Lung cancer risk comparison among male smokers between the "six-prefecture cohort" in Japan and the British physicians' cohort.

PubMed

Mizuno, S; Akiba, S; Hirayama, T

1989-12-01

We estimated the effective duration of cigarette smoking using the data of lung cancer mortality among male smokers of a large-scale cohort study in Japan and evaluated its role in the lung cancer risk difference between male smokers of the Japanese cohort and the British physicians' cohort. By selecting male cohort members who answered that they had started smoking at ages 18-22 (average = 20.3), the subjects of our analysis, which numbered 49,013, were made relatively homogeneous in terms of age at which smoking was started. Assuming lung cancer mortality to be proportional to the 4.5th power of the effective duration of cigarette smoking, i.e., (age-theta)4.5, as was proposed on the basis of the British cohort study by Doll and Peto, the parameter theta was estimated to be 29.4 for male smokers aged 40-64 in 1966; therefore, the estimated duration of cigarette smoking was, on average, 9.1 years (95% confidence interval = 5.8-11.6) shorter than that calculated from the reported age at which smoking was started. Our findings suggested that the low lung cancer mortality relative to daily cigarette consumption in Japan resulted from the shorter duration of cigarette smoking in the Japanese cohort, possibly due to the severe shortage of cigarettes during and shortly after World War II. Once the effective duration of cigarette smoking was adjusted, lung cancer mortality in the range of 5-34 cigarettes per day was fairly comparable to that observed among the cohort of male British physicians.

Geographic variation in cancer-related imaging: Veterans Affairs health care system versus Medicare.

PubMed

McWilliams, J Michael; Dalton, Jesse B; Landrum, Mary Beth; Frakt, Austin B; Pizer, Steven D; Keating, Nancy L

2014-12-02

Geographic variations in use of medical services have been interpreted as indirect evidence of wasteful care. Less overuse of services, however, may not be reliably associated with less geographic variation. To compare average use and geographic variation in use of cancer-related imaging between fee-for-service Medicare and the Department of Veterans Affairs (VA) health care system. Observational analysis of cancer-related imaging from 2003 to 2005 using Medicare and VA utilization data linked to cancer registry data. Multilevel models, adjusted for sociodemographic and tumor characteristics, were used to estimate mean differences in annual imaging use between cohorts of Medicare and VA patients within geographic areas and variation in use across areas for each cohort. 40 hospital referral regions. Older men with lung, colorectal, or prostate cancer, including 34,475 traditional Medicare beneficiaries (Medicare cohort) and 6835 VA patients (VA cohort). Per-patient count of imaging studies for which lung, colorectal, or prostate cancer was the primary diagnosis (each study weighted by a standardized price), and a direct measure of overuse-advanced imaging for prostate cancer at low risk for metastasis. Adjusted annual use of cancer-related imaging was lower in the VA cohort than in the Medicare cohort (price-weighted count, $197 vs. $379 per patient; P < 0.001), as was annual use of advanced imaging for prostate cancer at low risk for metastasis ($41 vs. $117 per patient; P < 0.001). Geographic variation in cancer-related imaging use was similar in magnitude in the VA and Medicare cohorts. Observational study design. Use of cancer-related imaging was lower in the VA health care system than in fee-for-service Medicare, but lower use was not associated with less geographic variation. Geographic variation in service use may not be a reliable indicator of the extent of overuse. Doris Duke Charitable Foundation and Department of Veterans Affairs Office of Policy and Planning.

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.

Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat: a phase 2 consortium/stand up 2 cancer study.

PubMed

Azad, Nilofer S; El-Khoueiry, Anthony; Yin, Jun; Oberg, Ann L; Flynn, Patrick; Adkins, Douglas; Sharma, Anup; Weisenberger, Daniel J; Brown, Thomas; Medvari, Prakriti; Jones, Peter A; Easwaran, Hariharan; Kamel, Ihab; Bahary, Nathan; Kim, George; Picus, Joel; Pitot, Henry C; Erlichman, Charles; Donehower, Ross; Shen, Hui; Laird, Peter W; Piekarz, Richard; Baylin, Stephen; Ahuja, Nita

2017-05-23

Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies. We conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 40 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10. An interim analysis indicated toxicity crossed the pre-specified safety boundary but was secondary to disease. A 2nd cohort with added eligibility restrictions was accrued: prior therapies were limited to no more than 2 or 3 (KRAS-mutated and KRAS-wildtype cancers, respectively) and <30% of liver involvement. The primary endpoint was RECIST response. Serial biopsies were performed at baseline and after 2 cycles of therapy. Forty-seven patients were enrolled (24:Cohort 1, 23:Cohort 2). Patients were heavily pre-treated (median prior therapies 4: Cohort 1 and 2.5: cohort 2). No responses were observed. Median progression-free survival was 1.9 months; overall survival was 5.6 and 8.3 months in Cohorts 1 and 2, respectively. Toxicity was tolerable and as expected. Unsupervised cluster analysis of serial tumor biopsies suggested greater DNA demethylation in patients with PFS above the median. In this first trial of CRC patients with combination epigenetic therapy, we show tolerable therapy without significant clinical activity as determined by RECIST responses. Reversal of hypermethylation was seen in a subset of patients and correlated with improved PFS.

Combination epigenetic therapy in metastatic colorectal cancer (mCRC) with subcutaneous 5-azacitidine and entinostat: a phase 2 consortium/stand Up 2 cancer study

PubMed Central

Azad, Nilofer S.; el-Khoueiry, Anthony; Yin, Jun; Oberg, Ann L.; Flynn, Patrick; Adkins, Douglas; Sharma, Anup; Weisenberger, Daniel J.; Brown, Thomas; Medvari, Prakriti; Jones, Peter A.; Easwaran, Hariharan; Kamel, Ihab; Bahary, Nathan; Kim, George; Picus, Joel; Pitot, Henry C.; Erlichman, Charles; Donehower, Ross; Shen, Hui; Laird, Peter W.; Piekarz, Richard; Baylin, Stephen; Ahuja, Nita

2017-01-01

Purpose Therapy with demethylating agent 5-azacitidine and histone deacetylase inhibitor entinostat shows synergistic re-expression of tumor-suppressor genes and growth inhibition in colorectal (CRC) cell lines and in vivo studies. Experimental Design We conducted a phase II, multi-institutional study of the combination in metastatic CRC patients. Subcutaneous azacitidine was administered at 40 mg/m2 days 1-5 and 8-10 and entinostat was given 7 mg orally on days 3 and 10. An interim analysis indicated toxicity crossed the pre-specified safety boundary but was secondary to disease. A 2nd cohort with added eligibility restrictions was accrued: prior therapies were limited to no more than 2 or 3 (KRAS-mutated and KRAS-wildtype cancers, respectively) and <30% of liver involvement. The primary endpoint was RECIST response. Serial biopsies were performed at baseline and after 2 cycles of therapy. Results Forty-seven patients were enrolled (24:Cohort 1, 23:Cohort 2). Patients were heavily pre-treated (median prior therapies 4: Cohort 1 and 2.5: cohort 2). No responses were observed. Median progression-free survival was 1.9 months; overall survival was 5.6 and 8.3 months in Cohorts 1 and 2, respectively. Toxicity was tolerable and as expected. Unsupervised cluster analysis of serial tumor biopsies suggested greater DNA demethylation in patients with PFS above the median. Conclusion In this first trial of CRC patients with combination epigenetic therapy, we show tolerable therapy without significant clinical activity as determined by RECIST responses. Reversal of hypermethylation was seen in a subset of patients and correlated with improved PFS. PMID:28186961

Procalcitonin decrease over 72 hours in US critical care units predicts fatal outcome in sepsis patients

PubMed Central

2013-01-01

Introduction Close monitoring and repeated risk assessment of sepsis patients in the intensive care unit (ICU) is important for decisions regarding care intensification or early discharge to the ward. We studied whether considering plasma kinetics of procalcitonin, a biomarker of systemic bacterial infection, over the first 72 critical care hours improved mortality prognostication of septic patients from two US settings. Methods This retrospective analysis included consecutively treated eligible adults with a diagnosis of sepsis from critical care units in two independent institutions in Clearwater, FL and Chicago, IL. Cohorts were used for derivation or validation to study the association between procalcitonin change over the first 72 critical care hours and mortality. Results ICU/in-hospital mortality rates were 29.2%/31.8% in the derivation cohort (n = 154) and 17.6%/29.4% in the validation cohort (n = 102). In logistic regression analysis of both cohorts, procalcitonin change was strongly associated with ICU and in-hospital mortality independent of clinical risk scores (Acute Physiology, Age and Chronic Health Evaluation IV or Simplified Acute Physiology Score II), with area under the curve (AUC) from 0.67 to 0.71. When procalcitonin decreased by at least 80%, the negative predictive value for ICU/in-hospital mortality was 90%/90% in the derivation cohort, and 91%/79% in the validation cohort. When procalcitonin showed no decrease or increased, the respective positive predictive values were 48%/48% and 36%/52%. Discussion In septic patients, procalcitonin kinetics over the first 72 critical care hours provide prognostic information beyond that available from clinical risk scores. If these observations are confirmed, procalcitonin monitoring may assist physician decision-making regarding care intensification or early transfer from the ICU to the floor. PMID:23787145

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

PubMed Central

2014-01-01

Introduction A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy. Methods Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis. Conclusion Our results suggest a role of PPARG gene in the development of SSc. PMID:24401602

Evaluation of physiotherapy in a prospective cohort of early axial spondyloarthritis. Data from the DESIR cohort.

PubMed

Escalas, Cécile; Dalichampt, Marie; Dougados, Maxime; Poiraudeau, Serge

2016-03-01

To evaluate the effect of physiotherapy on functional limitation in an observational cohort of early axial spondyloarthritis. prospective population-based cohort study. 708 patients with early axial spondyloarthritis between 2007 and 2010 naive of TNF blockers. early physiotherapy defined by at least eight supervised sessions of physical therapy during the first six months. the primary outcome was functional improvement defined by a relative improvement of at least 20% in BASFI at six months. Secondary outcomes were improvement in BASFI at one and two years and ASAS20 response criteria at six months. a propensity score of having physiotherapy was developed and multivariate analysis using propensity score weighting were used to assess the effect of physiotherapy on outcome. Overall, 166 (24%) patients had physiotherapy during the first six months. After using propensity score weighting, there was no functional improvement on the primary outcome in patients treated with early physical therapy (relative risk [IC95%]: 1.15 [0.91-1.45]). No differences were observed on secondary outcomes (relative risk [IC95%]: 0.94 [0.80-1.11]). It seems there is no functional benefit for patients with early spondyloarthritis to be treated early by physiotherapy in daily practice, even though the efficacy of physiotherapy has been shown in several randomized controlled studies. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Multivariate survivorship analysis using two cross-sectional samples.

PubMed

Hill, M E

1999-11-01

As an alternative to survival analysis with longitudinal data, I introduce a method that can be applied when one observes the same cohort in two cross-sectional samples collected at different points in time. The method allows for the estimation of log-probability survivorship models that estimate the influence of multiple time-invariant factors on survival over a time interval separating two samples. This approach can be used whenever the survival process can be adequately conceptualized as an irreversible single-decrement process (e.g., mortality, the transition to first marriage among a cohort of never-married individuals). Using data from the Integrated Public Use Microdata Series (Ruggles and Sobek 1997), I illustrate the multivariate method through an investigation of the effects of race, parity, and educational attainment on the survival of older women in the United States.

Breast feeding and intergenerational social mobility: what are the mechanisms?

PubMed

Sacker, A; Kelly, Y; Iacovou, M; Cable, N; Bartley, M

2013-09-01

To investigate the association between breast feeding and intergenerational social mobility and the possible mediating role of neurological and stress mechanisms. Secondary analysis of data from the 1958 and the 1970 British Cohort Studies. Longitudinal study of individuals born in Britain during 1 week in 1958 and 1970. 17 419 individuals participated in the 1958 cohort and 16 771 in the 1970 cohort. The effect of breast feeding on intergenerational social mobility from age 10/11 to age 33/34 was analysed after multiple imputations to fill in missing data and propensity score matching on a wide range of confounders measured in childhood (1958 cohort N=16 039-16 154; 1970 cohort N=16 255-16 361). Own Registrar General's Social Class (RGSC) at 33/34 years adjusted for father's RGSC at 10/11 years, gender and their interaction. Breastfed individuals were more likely to be upwardly mobile (1958 cohort: OR 1.24 95% CI 1.12 to 1.38; 1970 cohort: OR 1.24 95% CI 1.12 to 1.37) and less likely to be downwardly mobile (1958 cohort: OR 0.81 95% CI 0.73 to 0.90; 1970 cohort: OR 0.79 95% CI 0.71 to 0.88). In an ordinal regression model, markers of neurological development (cognitive test scores) and stress (emotional stress scores) accounted for approximately 36% of the relationship between breast feeding and social mobility. Breast feeding increased the odds of upward social mobility and decreased the odds of downward mobility. Consistent with a causal explanation, the findings were robust to matching on a large number of observable variables and effect sizes were alike for two cohorts with different social distributions of breast feeding. The effect was mediated in part through neurological and stress mechanisms.

Possibilities and considerations when merging dietary data from the world's two largest pregnancy cohorts: the Danish National Birth Cohort and the Norwegian Mother and Child Cohort Study.

PubMed

Olsen, Sjurdur F; Birgisdottir, Bryndis Eva; Halldorsson, Thorhallur I; Brantsaeter, Anne Lise; Haugen, Margaretha; Torjusen, Hanne; Petersen, Sesilje B; Strøm, Marin; Meltzer, Helle Margrete

2014-11-01

To elucidate the research possibilities when merging data on maternal diet from the Danish National Birth Cohort (DNBC) and the Norwegian Mother and Child Cohort Study (MoBa), through comparison of (i) the methodology used for dietary assessment and (ii) the estimated intake of selected food groups in the two cohorts. Qualitative and quantitative comparison of the two dietary databases. Two national prospective pregnancy cohorts. Denmark, Norway. Comparison of food intake using food frequency questionnaires (FFQs). The FFQs had overlapping time windows and a majority of the questions in the two FFQs were comparable. Calculation principles shared similar features, including the software used and use of global questions to calibrate intakes of different food groups. A total of 63 food groups were defined that could be compared across the two cohorts; these were further aggregated down to 31 broader groups. A comparison of food intakes (grams/d) showed 39, 74 and 141% lower daily intakes of fish, potatoes and rice, respectively, in DNBC vs. MoBa and 39, 54 and 65% higher daily intakes of milk, butter and potatoes in DNBC vs. MoBa. For most other food groups, differences in consumption data were below 20%. The two FFQs are to a large extent compatible and substantial differences in dietary habits were observed between the two cohorts. This may strengthen studies using pooled analysis to examine diet-disease relations. This is a conclusion of great importance given the colossal and costly task involved to establish each of these two cohorts. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Predictors of postherpetic neuralgia in patients with herpes zoster: a pooled analysis of prospective cohort studies from North and Latin America and Asia.

PubMed

Kawai, Kosuke; Rampakakis, Emmanouil; Tsai, Tsen-Fang; Cheong, Hee Jin; Dhitavat, Jittima; Covarrubias, Alejandro Ortiz; Yang, Lin; Cashat-Cruz, Miguel; Monsanto, Homero; Johnson, Kelly; Sampalis, John S; Acosta, Camilo J

2015-05-01

The most common complication of herpes zoster (HZ) is postherpetic neuralgia (PHN), a persistent pain that can substantially affect quality of life (QoL). This analysis aimed to evaluate predictors of PHN in HZ patients. A pooled analysis of prospective cohort studies of HZ patients aged ≥ 50 years from North America (Canada), Latin America (Brazil, Mexico, and Argentina), and Asia (Taiwan, South Korea, and Thailand) was performed. Patients within 14 days of rash onset were included. The incidence of PHN was defined as a worst pain score of ≥ 3, persisting/appearing at >90 days after rash onset. Socio-demographics, HZ disease characteristics, treatment, pain-related interference with activities of daily living, and health-related QoL were assessed. Of 702 patients with HZ, 148 (21.1%) developed PHN. Similar risks of PHN were observed across geographic regions. On multivariate analysis, older age, greater severity of pain at rash onset, employment status, walking problems at enrollment, and pain interference affecting social relationships were significantly associated with the development of PHN. In addition to older age and severe acute pain, this study suggests that impaired physical and social functioning from acute zoster pain may play a role in the development of PHN in this prospective cohort study of HZ patients from North and Latin America and Asia. Copyright © 2015. Published by Elsevier Ltd.

Cancer mortality in Minamata disease patients exposed to methylmercury through fish diet.

PubMed

Kinjo, Y; Akiba, S; Yamaguchi, N; Mizuno, S; Watanabe, S; Wakamiya, J; Futatsuka, M; Kato, H

1996-09-01

We report here a historical cohort study on cancer mortality among Minamata disease (MD) patients (n = 1,351) in Kagoshima and Kumamoto Prefectures of Japan. Taking into account their living area, sex, age and fish eating habits, the residents (n = 5,667; 40 years of age or over at 1966) living in coastal areas of Kagoshima, who consumed fish daily, were selected as a reference group from the six-prefecture cohort study conducted by Hirayama et al. The observation periods of the MD patients and of the reference group were from 1973 to 1984 and from 1970 to 1981, respectively. Survival analysis using the Poisson regression model was applied for comparison of mortality between the MD patients and the reference group. No excess of relative risk (RR) adjusted for attained age, sex and follow-up period was observed for mortality from all causes, all cancers, and non-cancers combined. Analysis of site-specific cancers showed a statistically significant decrease in mortality from stomach cancer among MD patients (RR, 0.49; 95% confidence interval, 0.26-0.94). In addition, a statistically significant eight-fold excess risk, based on 5 observed deaths, was noted for mortality from leukemia (RR, 8.35; 95 % confidence interval 1.61-43.3). It is, however, unlikely for these observed risks to be derived from methylmercury exposure only. Further studies are needed to understand the mechanisms involved in the observed risks among MD patients.

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.

Association between physical activity and risk of nonalcoholic fatty liver disease: a meta-analysis.

PubMed

Qiu, Shanhu; Cai, Xue; Sun, Zilin; Li, Ling; Zügel, Martina; Steinacker, Jürgen Michael; Schumann, Uwe

2017-09-01

Increased physical activity (PA) is a key element in the management of patients with nonalcoholic fatty liver disease (NAFLD); however, its association with NAFLD risk has not been systematically assessed. This meta-analysis of observational studies was to quantify this association with dose-response analysis. Electronic databases were searched to January 2017 for studies of adults reporting the risk of NAFLD in relation to PA with cohort or case-control designs. Studies that reported sex-specific data were included as separate studies. The overall risk estimates were pooled using a random-effects model, and the dose-response analysis was conducted to shape the quantitative relationship. A total of 6 cohort studies from 5 articles with 32,657 incident NAFLD cases from 142,781 participants, and 4 case-control studies from 3 articles with 382 NAFLD cases and 302 controls were included. Compared with the lowest PA level, the highest PA level was associated with a risk reduction of NAFLD in cohort [RR (risk ratio) 0.79, 95% CI (confidence interval) 0.71-0.89] and case-control studies [OR (odds ratio) 0.43, 95% CI 0.27-0.68]. For cohort studies, both highest and moderate PA levels were superior to the light one in lowering NAFLD risk ( p for interaction = 0.006 and 0.02, respectively), and there was a log-linear dose-response association ( p for nonlinearity = 0.10) between PA and NAFLD risk [RR 0.82 (95% CI 0.73-0.91) for every 500 metabolic equivalent (MET)-minutes/week increment in PA]. Increased PA may lead to a reduced risk of NAFLD in a dose-dependent manner, and the current guideline-recommended minimum PA level that approximates to 500 MET-minutes/week is able to moderately reduce the NAFLD risk.

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.

Development of quantitative exposure data for a pooled exposure-response analysis of 10 silica cohorts.

PubMed

Mannetje, Andrea 't; Steenland, Kyle; Checkoway, Harvey; Koskela, Riitta-Sisko; Koponen, Matti; Attfield, Michael; Chen, Jingqiong; Hnizdo, Eva; DeKlerk, Nicholas; Dosemeci, Mustafa

2002-08-01

Comprehensive quantitative silica exposure estimates over time, measured in the same units across a number of cohorts, would make possible a pooled exposure-response analysis for lung cancer. Such an analysis would help clarify the continuing controversy regarding whether silica causes lung cancer. Existing quantitative exposure data for 10 silica-exposed cohorts were retrieved from the original investigators. Occupation- and time-specific exposure estimates were either adopted/adapted or developed for each cohort, and converted to milligram per cubic meter (mg/m(3)) respirable crystalline silica. Quantitative exposure assignments were typically based on a large number (thousands) of raw measurements, or otherwise consisted of exposure estimates by experts (for two cohorts). Median exposure level of the cohorts ranged between 0.04 and 0.59 mg/m(3) respirable crystalline silica. Exposure estimates were partially validated via their successful prediction of silicosis in these cohorts. Existing data were successfully adopted or modified to create comparable quantitative exposure estimates over time for 10 silica-exposed cohorts, permitting a pooled exposure-response analysis. The difficulties encountered in deriving common exposure estimates across cohorts are discussed. Copyright 2002 Wiley-Liss, Inc.

Observational cohort study of the natural history of Niemann-Pick disease type C in the UK: a 5-year update from the UK clinical database.

PubMed

Imrie, Jackie; Heptinstall, Lesley; Knight, Stephen; Strong, Kate

2015-12-15

Niemann-Pick disease type C (NP-C) is a rare neurovisceral lipid storage disorder characterised by progressive, disabling neurological symptoms and premature death in most patients. During the last decade, national cohort studies have accrued a great deal of data on the symptomatology and natural history of NP-C. In an observational cohort study, we present a substantial update based on the clinical presentation and follow-up of all known UK-based patients with a confirmed diagnosis of NP-C who have been tracked on an electronic database at the Department of Genetic Medicine, University of Manchester, UK. Patients were stratified according to accepted age-at-neurological-onset categories. Data on patients' clinical signs and symptoms, medical history and genetic studies are summarised using descriptive methods. A total of 146 patients with NP-C were included, representing the full known UK NP-C cohort, as observed from database information between 1999 and the end of 2011: 72 patients (49 %) were alive at the end of the observation period. Among a total of 116 patients (79 %) who possessed at least one identified, disease-causing NP-C gene mutation, 114 (98 %) had NPC1 and two (2 %) had NPC2 mutations. Overall, 53/194 (27 %) identified mutations were novel. Six patients (4 %) had an early, non-neurological neonatal onset form of NP-C. The numbers (%) of patients with accepted age-at-neurological onset forms were: 8 (5 %) early-infantile onset, 51 (35 %) late-infantile onset, 42 (29 %) juvenile onset, and 25 (17 %) adolescent/adult onset. Fourteen patients diagnosed based on visceral symptoms and/or sibling history, confirmed in most cases by genetic analysis, did not have any neurological manifestations at last follow up (11 patients with mean [SD] age at last follow up 2.5 [1.8] years: 3 with mean [SD] age at death 20.8 [15.9] years). A total of 51 patients (35 %) received miglustat therapy. The mean (SD) overall treatment duration up to the end of the observation period was 2.6 (2.3) years. This UK cohort is the largest national NP-C cohort reported to date, and confirms the wide phenotypic variability of the disease, as reported in other countries. Further analyses are required to assess the impact of miglustat therapy on neurological disease progression.

Inter-cohort growth patterns of pharaoh cuttlefish Sepia pharaonis (Sepioidea: Sepiidae) in Eastern Arabian Sea.

PubMed

Sasikumarl, Geetha; Mohamed, K S; Bhat, U S

2013-03-01

Sepia pharaonis is an important commercial species endemic to the tropical Indo-Pacific region. Despite its commercial significance, only few information on natural populations is available. This study was aimed to describe the aspects of size-composition, length-weight relationship, catch rates, seasonal recruitment and inter-cohort growth patterns of S. pharaonis population (Clade C), distributed along the Eastern Arabian Sea (South-West coast of India). For this, the Dorsal Mantle Length (DML) and weight of cuttlefishes was obtained from commercial trawl catches, from April 2002 to October 2006. Data was analyzed by normal length-weight methods such as von Bertalanffy. A total of 12454 cuttlefishes, ranging in length from four to 41cm were analyzed. Size-composition patterns discriminated two pulses in recruitment to the fishery, discernible by a decrease in the monthly mean size of the population. The DMLs of the two seasonal cohorts were subjected to modal-progression analysis using the Bhattacharya's method for the estimation of growth. The estimated parameters Linfinity and K in von Bertalanffy Growth Function (VBGF) were used to model growth curves in length for the cohorts. The first cohort, (post-monsoon cohort) which supports the major fishery, was composed of medium-sized, fast growing individuals, whereas the second cohort (pre-monsoon cohort), comprised of slow growing and large-sized individuals. There were differential growth characteristics between the sexes and the life span was estimated at less than 2.3 years for males and 2.1 years for females. Negative allometric growth in weight (W) with length (L) was observed for males (W=0.33069.L2.5389) and females (W=0.32542.L26057). The females were heavier compared to males at any given mantle length, and the males were found to attain larger ultimate lengths. The major fishing season for cuttlefish was from May to November, when higher monthly catch rates of 1.67-13.02kg/h were observed in comparison with 0.03-0.85kg/h in December-April. Seasonal catch rates indicated a migratory life cycle ofS. pharaonis between offshore and inshore coastal zones.

Association analysis of ACE, ACTN3 and PPARGC1A gene polymorphisms in two cohorts of European strength and power athletes

PubMed Central

Jakaitiene, A; Aksenov, MO; Aksenova, AV; Druzhevskaya, AM; Astratenkova, IV; Egorova, ES; Gabdrakhmanova, LJ; Tubelis, L; Kucinskas, V; Utkus, A

2016-01-01

The performance of professional strength and power athletes is influenced, at least partly, by genetic components. The main aim of this study was to investigate individually and in combination the association of ACE (I/D), ACTN3 (R577X) and PPARGC1A (Gly482Ser) gene polymorphisms with strength/power-oriented athletes’ status in two cohorts of European athletes. A cohort of European Caucasians from Russia and Lithuania (161 athletes: by groups – weightlifters (87), powerlifters (60), throwers (14); by elite status – ‘elite’ (104), ‘sub-elite’ (57); and 1,202 controls) were genotyped for ACE, ACTN3 and PPARGC1A polymorphisms. Genotyping was performed by polymerase chain reaction and/or restriction fragment length polymorphism analysis. Statistically significant differences in ACTN3 (R577X) allele/genotype distribution were not observed in the whole cohort of athletes or between analysed groups separately when compared with controls. The odds ratio for athletes compared to controls of the ACE I/I genotype was 1.71 (95% CI 1.01-2.92) in the Russian cohort and for the ACE I/D genotype it was 2.35 (95% CI 1.10-5.06) in the Lithuanian cohort. The odds ratio of being a powerlifter in PPARGC1A Ser/Ser genotype carriers was 2.11 (95% CI: 1.09-4.09, P = 0.026). The ACTN3 (R577X) polymorphism is not associated with strength/power athletic status in two cohorts of European athletes. The ACE I/I genotype is probably the ‘preferable genotype’ for Russian athletes and the ACE I/D genotype for Lithuanian strength/power athletes. We found that the PPARGC1A (Gly482Ser) polymorphism is associated with strength/power athlete status. Specifically, the PPARGC1A Ser/Ser genotype is more favourable for powerlifters compared to controls. PMID:27601773

Associations of Glycemic Index and Load With Coronary Heart Disease Events: A Systematic Review and Meta-Analysis of Prospective Cohorts

PubMed Central

Mirrahimi, Arash; de Souza, Russell J.; Chiavaroli, Laura; Sievenpiper, John L.; Beyene, Joseph; Hanley, Anthony J.; Augustin, Livia S. A.; Kendall, Cyril W. C.; Jenkins, David J. A.

2012-01-01

Background Glycemic index (GI) and glycemic load (GL) have been associated with coronary heart disease (CHD) risk in some but not all cohort studies. We therefore assessed the association of GI and GL with CHD risk in prospective cohorts. Methods and Results We searched MEDLINE, EMBASE, and CINAHL (through April 5, 2012) and identified all prospective cohorts assessing associations of GI and GL with incidence of CHD. Meta-analysis of observational studies in epidemiology (MOOSE) methodologies were used. Relative measures of risk, comparing the group with the highest exposure (mean GI of cohorts=84.4 GI units, range 79.9 to 91; mean GL of cohorts=224.8, range 166 to 270) to the reference group (mean GI=72.3 GI units, range 68.1 to 77; mean GL=135.4, range 83 to 176), were pooled using random-effects models, expressed as relative risk (RR) with heterogeneity assessed by χ2 and quantified by I2. Subgroups included sex and duration of follow-up. Ten studies (n=240 936) were eligible. Pooled analyses showed an increase in CHD risk for the highest GI quantile compared with the lowest, with RR=1.11 (95% confidence interval [CI] 0.99 to 1.24) and for GL, RR=1.27 (95% CI 1.09 to 1.49), both with evidence of heterogeneity (I2>42%, P<0.07). Subgroup analyses revealed only a significant modification by sex, with the female cohorts showing significance for GI RR=1.26 (95% CI 1.12 to 1.41) and for GL RR=1.55 (95% CI 1.18 to 2.03). Conclusions High GI and GL diets were significantly associated with CHD events in women but not in men. Further studies are required to determine the relationship between GI and GL with CHD in men. PMID:23316283

Lung cancer incidence trends in Uruguay 1990-2014: An age-period-cohort analysis.

PubMed

Alonso, Rafael; Piñeros, Marion; Laversanne, Mathieu; Musetti, Carina; Garau, Mariela; Barrios, Enrique; Bray, Freddie

2018-05-11

Uruguay, a country with one of the highest lung cancer rates worldwide, initiated a series of comprehensive anti-smoking measures in 2005. We assess the tobacco control policies in the context of cohort-driven lung cancer incidence trends over a 25-year period, providing baseline predictions to 2035. Using data from the National Cancer Registry of Uruguay, an age-period-cohort analysis of trends 1990-2014 was performed. The NORDPRED package was used to predict the annual number of new cases of lung cancer and incidence rates up to 2035. In men, age-standardised (world) rates declined from a peak of 165.6 in 1995 to 103.1 by 2014, translating to a 70% reduction in the risk of lung cancer in men born in 1970 relative to the early-1940s. In females, rates increased steadily from 18.3 in 1991 to 30.0 by 2014, with successive increases in risk among generations of women born 1940-1960. There is however evidence of a decline in observed rates in women born recently. Extrapolations of the trends indicate an 8% reduction in the mean number of new lung cancer cases in men by 2035, but a 69% increase in women. Despite observed and predicted reductions in lung cancer incidence in Uruguayan men, rates among women are set to continue to increase, with a large rise in the annual number of female lung cancer diagnoses expected before 2035. There are signals of a diminishing risk among recent generations of women born after 1960. The current analysis provides important baseline information in assessing the future impact of the recent tobacco control initiatives in Uruguay. Copyright © 2018 Elsevier Ltd. All rights reserved.

Hypofractionation vs Conventional Radiation Therapy for Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Matched-Cohort Analysis

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

Janssens, Geert O., E-mail: g.janssens@rther.umcn.nl; Jansen, Marc H.; Lauwers, Selmer J.

2013-02-01

Purpose: Despite conventional radiation therapy, 54 Gy in single doses of 1.8 Gy (54/1.8 Gy) over 6 weeks, most children with diffuse intrinsic pontine glioma (DIPG) will die within 1 year after diagnosis. To reduce patient burden, we investigated the role of hypofractionation radiation therapy given over 3 to 4 weeks. A 1:1 matched-cohort analysis with conventional radiation therapy was performed to assess response and survival. Methods and Materials: Twenty-seven children, aged 3 to 14, were treated according to 1 of 2 hypofractionation regimens over 3 to 4 weeks (39/3 Gy, n=16 or 44.8/2.8 Gy, n=11). All patients had symptomsmore » for {<=}3 months, {>=}2 signs of the neurologic triad (cranial nerve deficit, ataxia, long tract signs), and characteristic features of DIPG on magnetic resonance imaging. Twenty-seven patients fulfilling the same diagnostic criteria and receiving at least 50/1.8 to 2.0 Gy were eligible for the matched-cohort analysis. Results: With hypofractionation radiation therapy, the overall survival at 6, 9, and 12 months was 74%, 44%, and 22%, respectively. Progression-free survival at 3, 6, and 9 months was 77%, 43%, and 12%, respectively. Temporary discontinuation of steroids was observed in 21 of 27 (78%) patients. No significant difference in median overall survival (9.0 vs 9.4 months; P=.84) and time to progression (5.0 vs 7.6 months; P=.24) was observed between hypofractionation vs conventional radiation therapy, respectively. Conclusions: For patients with newly diagnosed DIPG, a hypofractionation regimen, given over 3 to 4 weeks, offers equal overall survival with less treatment burden compared with a conventional regimen of 6 weeks.« less

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.

Improved human observer performance in digital reconstructed radiograph verification in head and neck cancer radiotherapy.

PubMed

Sturgeon, Jared D; Cox, John A; Mayo, Lauren L; Gunn, G Brandon; Zhang, Lifei; Balter, Peter A; Dong, Lei; Awan, Musaddiq; Kocak-Uzel, Esengul; Mohamed, Abdallah Sherif Radwan; Rosenthal, David I; Fuller, Clifton David

2015-10-01

Digitally reconstructed radiographs (DRRs) are routinely used as an a priori reference for setup correction in radiotherapy. The spatial resolution of DRRs may be improved to reduce setup error in fractionated radiotherapy treatment protocols. The influence of finer CT slice thickness reconstruction (STR) and resultant increased resolution DRRs on physician setup accuracy was prospectively evaluated. Four head and neck patient CT-simulation images were acquired and used to create DRR cohorts by varying STRs at 0.5, 1, 2, 2.5, and 3 mm. DRRs were displaced relative to a fixed isocenter using 0-5 mm random shifts in the three cardinal axes. Physician observers reviewed DRRs of varying STRs and displacements and then aligned reference and test DRRs replicating daily KV imaging workflow. A total of 1,064 images were reviewed by four blinded physicians. Observer errors were analyzed using nonparametric statistics (Friedman's test) to determine whether STR cohorts had detectably different displacement profiles. Post hoc bootstrap resampling was applied to evaluate potential generalizability. The observer-based trial revealed a statistically significant difference between cohort means for observer displacement vector error ([Formula: see text]) and for [Formula: see text]-axis [Formula: see text]. Bootstrap analysis suggests a 15% gain in isocenter translational setup error with reduction of STR from 3 mm to [Formula: see text]2 mm, though interobserver variance was a larger feature than STR-associated measurement variance. Higher resolution DRRs generated using finer CT scan STR resulted in improved observer performance at shift detection and could decrease operator-dependent geometric error. Ideally, CT STRs [Formula: see text]2 mm should be utilized for DRR generation in the head and neck.

Stereotyped Motor Behaviors Associated with Autism in High-Risk Infants: A Pilot Videotape Analysis of a Sibling Sample

ERIC Educational Resources Information Center

Loh, Alvin; Soman, Teesta; Brian, Jessica; Bryson, Susan E.; Roberts, Wendy; Szatmari, Peter; Smith, Isabel M.; Zwaigenbaum, Lonnie

2007-01-01

This study examined motor behaviors in a longitudinal cohort of infant siblings of children with autism. Stereotypic movements and postures occurring during standardized observational assessments at 12 and 18 months were coded from videotapes. Participants included eight infant siblings later diagnosed with autism spectrum disorder (ASD), a random…

The relationship between interviewer-respondent race match and reporting of energy intake using food frequency questionnaires in the rural South United States

USDA-ARS?s Scientific Manuscript database

The purpose of the observational study was to determine whether interviewer race influences food frequency questionnaire (FFQ) reporting accuracy in a Deep South, largely African American cohort. A secondary analysis was conducted to investigate the influence of interviewer race on energy reporting ...

Impact of Exercise Counseling on Physical Function in Chronic Kidney Disease: An Observational Study

PubMed Central

Storsley, Leroy J.; Hiebert, Brett M.; Nelko, Serena; Cheskin, Lawrence J.; McAdams-DeMarco, Mara A.; Rigatto, Claudio

2018-01-01

Background: Individuals with chronic kidney disease (CKD) have low levels of physical activity and physical function. Although guidelines endorse exercise counseling for individuals with CKD, it is not yet part of routine care. Objective: We investigated the effect of attending a real-life exercise counseling clinic (ECC) on physical function in individuals with CKD. Design: Retrospective analysis of prospectively collected observational data with quasi-experimental design. Setting and Participants: Patients with all stages of CKD registered in a large provincial renal program were eligible. The exposed cohort who attended the ECC between January 1, 2011, and March 15, 2014, included 214 individuals. The control cohort included 292 individuals enrolled in an observational study investigating longitudinal change in frailty during the same time period. Predictor/Factor: Attendance at an ECC. Outcomes and Measurements: Change in physical function as measured by Short Physical Performance Battery (SPPB) score, physical activity level (Human Activity Profile [HAP]/Physical Activity Scale for the Elderly [PASE]), and health-related quality of life (HRQOL; EQ5D/VAS) over 1 year. Results: Eighty-seven individuals in the ECC cohort and 125 participants in the control cohort completed 1-year follow-up. Baseline median SPPB score was 10 (interquartile range [IQR]: 9-12) and 9 (IQR: 7-11) in the ECC and control cohorts, respectively (P < .01). At 1 year, SPPB scores were 10 (IQR: 8-12) and 9 (IQR: 6-11) in the ECC and control cohorts, respectively (P = .04). Mean change in SPPB over 1 year was not significantly different between groups: −0.33 (95% confidence interval [CI]: −0.81 to 0.15) in ECC and −0.22 (95% CI: −0.61 to 0.17) in control (P = .72). There was no significant difference in the proportion of individuals in each cohort with an increase/decrease in SPPB score over time. There was no significant change in physical activity or HRQOL over time between groups. Limitations: Quasi-experimental design, low rate of follow-up attendance. Conclusions: In this pragmatic study, exercise counseling had no significant effect on change in SPPB score, suggesting that a single exercise counseling session alone is inadequate to improve physical function in CKD. PMID:29487746

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.

Novel mutations and phenotypic associations identified through APC, MUTYH, NTHL1, POLD1, POLE gene analysis in Indian Familial Adenomatous Polyposis cohort.

PubMed

Khan, Nikhat; Lipsa, Anuja; Arunachal, Gautham; Ramadwar, Mukta; Sarin, Rajiv

2017-05-22

Colo-Rectal Cancer is a common cancer worldwide with 5-10% cases being hereditary. Familial Adenomatous Polyposis (FAP) syndrome is due to germline mutations in the APC or rarely MUTYH gene. NTHL1, POLD1, POLE have been recently reported in previously unexplained FAP cases. Unlike the Caucasian population, FAP phenotype and its genotypic associations have not been widely studied in several geoethnic groups. We report the first FAP cohort from South Asia and the only non-Caucasian cohort with comprehensive analysis of APC, MUTYH, NTHL1, POLD1, POLE genes. In this cohort of 112 individuals from 53 FAP families, we detected germline APC mutations in 60 individuals (45 families) and biallelic MUTYH mutations in 4 individuals (2 families). No NTHL1, POLD1, POLE mutations were identified. Fifteen novel APC mutations and a new Indian APC mutational hotspot at codon 935 were identified. Eight very rare FAP phenotype or phenotypes rarely associated with mutations outside specific APC regions were observed. APC genotype-phenotype association studies in different geo-ethnic groups can enrich the existing knowledge about phenotypic consequences of distinct APC mutations and guide counseling and risk management in different populations. A stepwise cost-effective mutation screening approach is proposed for genetic testing of south Asian FAP patients.

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.

Citrus fruit intake and bladder cancer risk: a meta-analysis of observational studies.

PubMed

Liang, Sudong; Lv, Gaofei; Chen, Weikai; Jiang, Jianxin; Wang, Jingqun

2014-11-01

Epidemiological studies have investigated the association between citrus fruit and bladder cancer risk; however, the results are inconsistent. To assess these issues, we conducted a meta-analysis of currently available studies. We identified relevant articles by searching the MEDLINE and EMBASE databases. We calculated the summary relative risk (RR) with 95% confidence interval (95% CI) using a random effect model. We included eight case-control studies and six cohort studies in the meta-analysis. There was a significant inverse association between citrus fruit intake and bladder cancer risk in all pooled studies (RR: 0.85; 95% CI, 0.76-0.94) and case-control studies (RR: 0.77; 95% CI, 0.64-0.92), but not in the cohort studies (RR: 0.96; 95% CI, 0.87-1.07). Our results suggest that citrus fruit intake is related to decreased bladder cancer risk. Subsequent well-designed, large prospective studies are needed to obtain better understanding of this relationship.

Screening LGI1 in a cohort of 26 lateral temporal lobe epilepsy patients with auditory aura from Turkey detects a novel de novo mutation.

PubMed

Kesim, Yesim F; Uzun, Gunes Altiokka; Yucesan, Emrah; Tuncer, Feyza N; Ozdemir, Ozkan; Bebek, Nerses; Ozbek, Ugur; Iseri, Sibel A Ugur; Baykan, Betul

2016-02-01

Autosomal dominant lateral temporal lobe epilepsy (ADLTE) is an autosomal dominant epileptic syndrome characterized by focal seizures with auditory or aphasic symptoms. The same phenotype is also observed in a sporadic form of lateral temporal lobe epilepsy (LTLE), namely idiopathic partial epilepsy with auditory features (IPEAF). Heterozygous mutations in LGI1 account for up to 50% of ADLTE families and only rarely observed in IPEAF cases. In this study, we analysed a cohort of 26 individuals with LTLE diagnosed according to the following criteria: focal epilepsy with auditory aura and absence of cerebral lesions on brain MRI. All patients underwent clinical, neuroradiological and electroencephalography examinations and afterwards they were screened for mutations in LGI1 gene. The single LGI1 mutation identified in this study is a novel missense variant (NM_005097.2: c.1013T>C; p.Phe338Ser) observed de novo in a sporadic patient. This is the first study involving clinical analysis of a LTLE cohort from Turkey and genetic contribution of LGI1 to ADLTE phenotype. Identification of rare LGI1 gene mutations in sporadic cases supports diagnosis as ADTLE and draws attention to potential familial clustering of ADTLE in suggestive generations, which is especially important for genetic counselling. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Long working hours and depressive symptoms: systematic review and meta-analysis of published studies and unpublished individual participant data.

PubMed

Virtanen, Marianna; Jokela, Markus; Madsen, Ida Eh; Magnusson Hanson, Linda L; Lallukka, Tea; Nyberg, Solja T; Alfredsson, Lars; Batty, G David; Bjorner, Jakob B; Borritz, Marianne; Burr, Hermann; Dragano, Nico; Erbel, Raimund; Ferrie, Jane E; Heikkilä, Katriina; Knutsson, Anders; Koskenvuo, Markku; Lahelma, Eero; Nielsen, Martin L; Oksanen, Tuula; Pejtersen, Jan H; Pentti, Jaana; Rahkonen, Ossi; Rugulies, Reiner; Salo, Paula; Schupp, Jürgen; Shipley, Martin J; Siegrist, Johannes; Singh-Manoux, Archana; Suominen, Sakari B; Theorell, Töres; Vahtera, Jussi; Wagner, Gert G; Wang, Jian Li; Yiengprugsawan, Vasoontara; Westerlund, Hugo; Kivimäki, Mika

2018-05-01

Objectives This systematic review and meta-analysis combined published study-level data and unpublished individual-participant data with the aim of quantifying the relation between long working hours and the onset of depressive symptoms. Methods We searched PubMed and Embase for published prospective cohort studies and included available cohorts with unpublished individual-participant data. We used a random-effects meta-analysis to calculate summary estimates across studies. Results We identified ten published cohort studies and included unpublished individual-participant data from 18 studies. In the majority of cohorts, long working hours was defined as working ≥55 hours per week. In multivariable-adjusted meta-analyses of 189 729 participants from 35 countries [96 275 men, 93 454 women, follow-up ranging from 1-5 years, 21 747 new-onset cases), there was an overall association of 1.14 (95% confidence interval (CI) 1.03-1.25] between long working hours and the onset of depressive symptoms, with significant evidence of heterogeneity (I 2 =45.1%, P=0.004). A moderate association between working hours and depressive symptoms was found in Asian countries (1.50, 95% CI 1.13-2.01), a weaker association in Europe (1.11, 95% CI 1.00-1.22), and no association in North America (0.97, 95% CI 0.70-1.34) or Australia (0.95, 95% CI 0.70-1.29). Differences by other characteristics were small. Conclusions This observational evidence suggests a moderate association between long working hours and onset of depressive symptoms in Asia and a small association in Europe.

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

Evaluation of community-acquired sepsis by PIRO system in the emergency department.

PubMed

Chen, Yun-Xia; Li, Chun-Sheng

2013-09-01

The predisposition, infection/insult, response, and organ dysfunction (PIRO) staging system for septic patients allows grouping of heterogeneous patients into homogeneous subgroups. The purposes of this single-center, prospective, observational cohort study were to create a PIRO system for patients with community-acquired sepsis (CAS) presenting to the emergency department (ED) and assess its prognostic and stratification capabilities. Septic patients were enrolled and allocated to derivation (n = 831) or validation (n = 860) cohorts according to their enrollment dates. The derivation cohort was used to identify independent predictors of mortality and create a PIRO system by binary logistic regression analysis, and the prognostic performance of PIRO was investigated in the validation cohort by receiver operator characteristic (ROC) curve. Ten independent predictors of 28-day mortality were identified. The PIRO system combined the components of predisposition (age, chronic obstructive pulmonary disease, hypoalbuminemia), infection (central nervous system infection), response (temperature, procalcitonin), and organ dysfunction (brain natriuretic peptide, troponin I, mean arterial pressure, Glasgow coma scale score). The area under the ROC of PIRO was 0.833 for the derivation cohort and 0.813 for the validation cohort. There was a stepwise increase in 28-day mortality with increasing PIRO score and the differences between the low- (PIRO 0-10), intermediate- (11-20), and high- (>20) risk groups were very significant in both cohorts (p < 0.01). The present study demonstrates that this PIRO system is valuable for prognosis and risk stratification in patients with CAS in the ED.

Consumption of Yogurt and the Incident Risk of Cardiovascular Disease: A Meta-Analysis of Nine Cohort Studies.

PubMed

Wu, Lei; Sun, Dali

2017-03-22

Previous systematic reviews and meta-analyses have evaluated the association of dairy consumption and the risk of cardiovascular disease (CVD). However, the findings were inconsistent. No quantitative analysis has specifically assessed the effect of yogurt intake on the incident risk of CVD. We searched the PubMed and the Embase databases from inception to 10 January 2017. A generic inverse-variance method was used to pool the fully-adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs) with a random-effects model. A generalized least squares trend estimation model was used to calculate the specific slopes in the dose-response analysis. The present systematic review and meta-analysis identified nine prospective cohort articles involving a total of 291,236 participants. Compared with the lowest category, highest category of yogurt consumption was not significantly related with the incident risk of CVD, and the RR (95% CI) was 1.01 (0.95, 1.08) with an evidence of significant heterogeneity (I² = 52%). However, intake of ≥200 g/day yogurt was significantly associated with a lower risk of CVD in the subgroup analysis. There was a trend that a higher level of yogurt consumption was associated with a lower incident risk of CVD in the dose-response analysis. A daily dose of ≥200 g yogurt intake might be associated with a lower incident risk of CVD. Further cohort studies and randomized controlled trials are still demanded to establish and confirm the observed association in populations with different characteristics.

Consumption of Yogurt and the Incident Risk of Cardiovascular Disease: A Meta-Analysis of Nine Cohort Studies

PubMed Central

Wu, Lei; Sun, Dali

2017-01-01

Previous systematic reviews and meta-analyses have evaluated the association of dairy consumption and the risk of cardiovascular disease (CVD). However, the findings were inconsistent. No quantitative analysis has specifically assessed the effect of yogurt intake on the incident risk of CVD. We searched the PubMed and the Embase databases from inception to 10 January 2017. A generic inverse-variance method was used to pool the fully-adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs) with a random-effects model. A generalized least squares trend estimation model was used to calculate the specific slopes in the dose-response analysis. The present systematic review and meta-analysis identified nine prospective cohort articles involving a total of 291,236 participants. Compared with the lowest category, highest category of yogurt consumption was not significantly related with the incident risk of CVD, and the RR (95% CI) was 1.01 (0.95, 1.08) with an evidence of significant heterogeneity (I2 = 52%). However, intake of ≥200 g/day yogurt was significantly associated with a lower risk of CVD in the subgroup analysis. There was a trend that a higher level of yogurt consumption was associated with a lower incident risk of CVD in the dose-response analysis. A daily dose of ≥200 g yogurt intake might be associated with a lower incident risk of CVD. Further cohort studies and randomized controlled trials are still demanded to establish and confirm the observed association in populations with different characteristics. PMID:28327514

Revisiting the “Golden Hour”: An Evaluation of Out-of-Hospital Time in Shock and Traumatic Brain Injury

PubMed Central

Newgard, Craig D.; Meier, Eric N.; Bulger, Eileen M.; Buick, Jason; Sheehan, Kellie; Lin, Steve; Minei, Joseph P.; Barnes-Mackey, Roxy A.; Brasel, Karen

2015-01-01

Study Objective We evaluated shock and traumatic brain injury (TBI) patients previously enrolled in an out-of-hospital clinical trial to test the association between out-of-hospital time and outcome. Methods This was a secondary analysis of shock and TBI patients ≥ 15 years enrolled in a Resuscitation Outcomes Consortium out-of-hospital clinical trial by 81 EMS agencies transporting to 46 Level I and II trauma centers in 11 sites (May 2006 through May 2009). Inclusion criteria were: SBP ≤ 70 mmHg or SBP 71 - 90 mmHg with heart rate ≥ 108 beats per minute (shock cohort) and Glasgow Coma Scale score ≤ 8 (TBI cohort); patients meeting both criteria were placed in the shock cohort. Primary outcomes were 28-day mortality (shock cohort) and 6-month Glasgow Outcome Scale - Extended (GOSE) ≤ 4 (TBI cohort). Results There were 778 patients in the shock cohort (26% 28-day mortality) and 1,239 patients in the TBI cohort (53% 6-month GOSE ≤ 4). Out-of-hospital time > 60 minutes was not associated with worse outcomes after accounting for important confounders in the shock cohort (adjusted odds ratio [aOR] 1.42, 95% CI 0.77-2.62) or TBI cohort (aOR 0.80, 95% CI 0.52-1.21). However, shock patients requiring early critical hospital resources and arriving > 60 minutes had higher 28-day mortality (aOR 2.37, 95% CI 1.05-5.37); this finding was not observed among a similar TBI subgroup. Conclusions Among out-of-hospital trauma patients meeting physiologic criteria for shock and TBI, there was no association between time and outcome. However, the subgroup of shock patients requiring early critical resources arriving after 60 minutes had higher mortality. PMID:25596960

Quality of Reporting and Study Design of CKD Cohort Studies Assessing Mortality in the Elderly Before and After STROBE: A Systematic Review.

PubMed

Rao, Anirudh; Brück, Katharina; Methven, Shona; Evans, Rebecca; Stel, Vianda S; Jager, Kitty J; Hooft, Lotty; Ben-Shlomo, Yoav; Caskey, Fergus

2016-01-01

The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement was published in October 2007 to improve quality of reporting of observational studies. The aim of this review was to assess the impact of the STROBE statement on observational study reporting and study design quality in the nephrology literature. Systematic literature review. European and North American, Pre-dialysis Chronic Kidney Disease (CKD) cohort studies. Studies assessing the association between CKD and mortality in the elderly (>65 years) published from 1st January 2002 to 31st December 2013 were included, following systematic searching of MEDLINE & EMBASE. Time period before and after the publication of the STROBE statement. Quality of study reporting using the STROBE statement and quality of study design using the Newcastle Ottawa Scale (NOS), Scottish Intercollegiate Guidelines Network (SIGN) and Critical Appraisal Skills Programme (CASP) tools. 37 papers (11 Pre & 26 Post STROBE) were identified from 3621 potential articles. Only four of the 22 STROBE items and their sub-criteria (objectives reporting, choice of quantitative groups and description of and carrying out sensitivity analysis) showed improvements, with the majority of items showing little change between the period before and after publication of the STROBE statement. Pre- and post-period analysis revealed a Manuscript STROBE score increase (median score 77.8% (Inter-quartile range [IQR], 64.7-82.0) vs 83% (IQR, 78.4-84.9, p = 0.05). There was no change in quality of study design with identical median scores in the two periods for NOS (Manuscript NOS score 88.9), SIGN (Manuscript SIGN score 83.3) and CASP (Manuscript CASP score 91.7) tools. Only 37 Studies from Europe and North America were included from one medical specialty. Assessment of study design largely reliant on good reporting. This study highlights continuing deficiencies in the reporting of STROBE items and their sub-criteria in cohort studies in nephrology. There was weak evidence of improvement in the overall reporting quality, with no improvement in methodological quality of CKD cohort studies between the period before and after publication of the STROBE statement.

Factors effecting impact of Aspergillus fumigatus sensitization in cystic fibrosis.

PubMed

Kanthan, Senthooran Kathirgama; Bush, Andrew; Kemp, Michael; Buchdahl, Roger

2007-09-01

The clinical impact of Aspergillus fumigatus (Af) sensitization in cystic fibrosis (CF) is controversial. We examined the effect of Af sensitization (Afs) on pulmonary function and growth using a retrospective cohort analysis over two 5-year study periods: 1996-2000 (19 Afs cases and 19 controls) and 2001-2005 (24 Afs cases and 23 controls). Sensitization was defined as Af specific radioallergosorbent test (RAST) >or= 17.5 iu/ml and total serum IgE level >or=150 iu/ml. We examined the impact of changing treatment schedules over these periods. Afs cases had lower median FEV(1) %predicted (%PR) compared to matched controls 1996: 67 versus 80, P < 0.01; 2001: 78 versus 93, P < 0.01. Afs cases in the 2001 cohort had a higher FEV(1) %PR compared to Afs cases in the 1996 cohort: 78 versus 67, P < 0.01. For the 1996 Afs cohort FEV(1) %PR fell significantly over 5 years but not for the 2001 Afs cohort. Af RAST and total IgE reflected the changes in pulmonary function. Children in the 2001 Afs cohort were prescribed significantly more oral antifungal treatment (odds ratio 4.3, 95%CI 1.2-15.7, P = 0.03). Afs children continue to have poorer lung function compared to controls but this observational, hypothesis generating study, suggests that the use of antifungal treatment is associated with better lung function. (c) 2007 Wiley-Liss, Inc.

Human milk feeding protects very low-birth-weight infants from retinopathy of prematurity: a pre-post cohort analysis.

PubMed

Ginovart, Gemma; Gich, Ignasi; Verd, Sergio

2016-12-01

To examine the effect of early human milk (HM) feeding on the incidence of retinopathy of prematurity (ROP) among very low-birth-weight (VLBW) infants. Observational cohort research in a Level III neonatal intensive care unit. A total of 186 infants were enrolled in this pre-post cohort study (114 infants were included in the HM-fed group and 72 in the formula-fed group). ROP, type of feeding (early exclusive HM versus any formula), and potential confounding variables were measured. Differences between groups were explored. The clinical characteristics of the neonates did not differ between the two groups. By bivariate analysis, HM feeding was associated with 75% lower odds of Stage 2 or 3 ROP (OR = 0.25, 95% CI: 0.091 to 0.705; p = 0.009) At multivariate logistic regression, type of milk feeding retained significance, exclusive HM being protective with p = 0.002. This study found an association between early exposure to formula in VLBW infants and ROP. An initial HM diet, devoid of cow milk-containing products before achieving full enteral feeding, may help prevent ROP.

Trends in U.S., Past-Year Marijuana Use from 1985–2009; An Age-Period-Cohort Analysis

PubMed Central

Miech, Richard; Koester, Stephen

2014-01-01

Background We present a formal age-period-cohort analysis to examine if the recent increase in past-year marijuana use among the young is specific to the younger generation or if, instead, it is part of a general increase present across cohorts of all ages. This is the first age-period-cohort analysis of past-year marijuana use that includes adult trends from 2001–09. 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 25 year time span from 1985–2009 and uses the recently developed ‘intrinsic estimator’ algorithm to estimate independent effects of age, period, and cohort. Results The recent increase in past-year marijuana use is not unique to the youngest birth cohorts. An independent, positive influence of cohort membership on past-year marijuana use, net of historical period and age effects, is smaller for today’s youngest cohorts than it was for the cohorts that came immediately before, and, in fact, is at its lowest level in three decades. The recent increase in marijuana use among the young is more consistent with a historical period effect that has acted across all cohorts. Period and cohort trends differ substantially for Hispanics. Conclusions The major forces that drive trends in past-year marijuana use are moving away from cohort-specific factors and toward broad-based influences that affect cohorts of all ages. Strategic public health and policy efforts aimed at countering the recent increase in past-year marijuana use should do the same. PMID:22361212

A Comparative Analysis of Collaborative Leadership Skills Employed by Graduates of Cohort Based and Non-Cohort Based Doctoral Programs in Eduational Leadership

ERIC Educational Resources Information Center

Breton Caminos, Michelle Evangeline

2015-01-01

This qualitative comparative case analysis investigates the leadership approaches of the graduates of two educational leadership doctoral programs in Upstate New York--one a cohort-modeled program, the other a non-cohort program--with specific attention to collaboration. Responses from participants indicate key differences in Engaging Communities,…

Trends in mortality from septicaemia and pneumonia with economic development: an age-period-cohort analysis.

PubMed

Wong, Irene O L; Cowling, Benjamin J; Leung, Gabriel M; Schooling, C Mary

2012-01-01

Hong Kong population has experienced drastic changes in its economic development in the 1940s. Taking advantage of Hong Kong's unique demographic and socioeconomic history, characterized by massive, punctuated migration waves from Southern China, and recent, rapid transition from a pre-industrialized society to the first ethnic Chinese community reaching "first world" status over the last 60 years (i.e., in two or three generations), we examined the longitudinal trends in infection related mortality including septicemia compared to trends in non-bacterial pneumonia to generate hypotheses for further testing in other recently transitioned economies and to provide generalized aetiological insights on how economic transition affects infection-related mortality. We used deaths from septicemia and pneumonia not specified as bacterial, and population figures in Hong Kong from 1976-2005. We fitted age-period-cohort models to decompose septicemia and non-bacterial pneumonia mortality rates into age, period and cohort effects. Septicaemia-related deaths increased exponentially with age, with a downturn by period. The birth cohort curves had downward inflections in both sexes in the 1940s, with a steeper deceleration for women. Non-bacterial pneumonia-related deaths also increased exponentially with age, but the birth cohort patterns showed no downturns for those born in the 1940s. The observed changes appeared to suggest that better early life conditions may enable better development of adaptive immunity, thus enhancing immunity against bacterial infections, with greater benefits for women than men. Given the interaction between the immune system and the gonadotropic axis, these observations are compatible with the hypothesis that upregulation of the gonadotropic axis underlies some of the changes in disease patterns with economic development.

X-chromosome Forkhead Box P3 polymorphisms associate with atopy in girls in three Dutch birth cohorts.

PubMed

Bottema, R W B; Kerkhof, M; Reijmerink, N E; Koppelman, G H; Thijs, C; Stelma, F F; Smit, H A; Brunekreef, B; van Schayck, C P; Postma, D S

2010-07-01

The Forkhead Box P3 (FOXP3) gene, located on the X-chromosome, encodes a transcription factor that directs T cells toward a regulatory phenotype. Regulatory T cells may suppress development of atopy. We evaluated whether single-nucleotide polymorphisms (SNPs) of FOXP3 are associated with atopy development in childhood. Seven SNPs in FOXP3 were genotyped in 3062 children (51% boys) participating in the Allergenic study, which consists of three Dutch birth cohorts (PIAMA, PREVASC and KOALA). Association of FOXP3 SNPs with total serum IgE and sensitisation (presence of specific serum IgE to egg, milk, and indoor, i.e. house-dust mite, cat, and/or dog allergens) was investigated at ages 1, 2, 4, and 8. Analysis of variance and logistic regression were performed, stratified for gender. Our most consistent finding was observed for sensitisation to egg and indoor allergens. In girls, five FOXP3 SNPs (rs5906761, rs2294021, rs2294019, rs6609857 and rs3761548) were significantly associated with sensitisation to egg at ages 1 and 2 and with sensitisation to indoor allergens at age 2 (P < 0.05), but not at 4 and 8, a finding that was observed across the three cohorts. Rs5906761 and rs2294021 were associated with remission of sensitisation to food allergens in boys, as tested in the PIAMA cohort. This is the first study showing across three cohorts that X-chromosomal FOXP3 genotypes may contribute to development of sensitisation against egg and indoor allergens in girls in early childhood. In addition, an association with remission of sensitisation to food allergens existed in boys only.

Use of benzodiazepine and risk of cancer: A meta-analysis of observational studies.

PubMed

Kim, Hong-Bae; Myung, Seung-Kwon; Park, Yon Chul; Park, Byoungjin

2017-02-01

Several observational epidemiological studies have reported inconsistent results on the association between the use of benzodiazepine and the risk of cancer. We investigated the association by using a meta-analysis. We searched PubMed, EMBASE, and the bibliographies of relevant articles to locate additional publications in January 2016. Three evaluators independently reviewed and selected eligible studies based on predetermined selection criteria. Of 796 articles meeting our initial criteria, a total of 22 observational epidemiological studies with 18 case-control studies and 4 cohort studies were included in the final analysis. Benzodiazepine use was significantly associated with an increased risk of cancer (odds ratio [OR] or relative risk [RR] 1.19; 95% confidence interval 1.16-1.21) in a random-effects meta-analysis of all studies. Subgroup meta-analyses by various factors such as study design, type of case-control study, study region, and methodological quality of study showed consistent findings. Also, a significant dose-response relationship was observed between the use of benzodiazepine and the risk of cancer (p for trend <0.01). The current meta-analysis of observational epidemiological studies suggests that benzodiazepine use is associated with an increased risk of cancer. © 2016 UICC.

Challenges in translating endpoints from trials to observational cohort studies in oncology

PubMed Central

Ording, Anne Gulbech; Cronin-Fenton, Deirdre; Ehrenstein, Vera; Lash, Timothy L; Acquavella, John; Rørth, Mikael; Sørensen, Henrik Toft

2016-01-01

Clinical trials are considered the gold standard for examining drug efficacy and for approval of new drugs. Medical databases and population surveillance registries are valuable resources for post-approval observational research, which are increasingly used in studies of benefits and risk of new cancer drugs. Here, we address the challenges in translating endpoints from oncology trials to observational studies. Registry-based cohort studies can investigate real-world safety issues – including previously unrecognized concerns – by examining rare endpoints or multiple endpoints at once. In contrast to clinical trials, observational cohort studies typically do not exclude real-world patients from clinical practice, such as old and frail patients with comorbidity. The observational cohort study complements the clinical trial by examining the effectiveness of interventions applied in clinical practice and by providing evidence on long-term clinical outcomes, which are often not feasible to study in a clinical trial. Various endpoints can be included in clinical trials, such as hard endpoints, soft endpoints, surrogate endpoints, and patient-reported endpoints. Each endpoint has it strengths and limitations for use in research studies. Endpoints used in oncology trials are often not applicable in observational cohort studies which are limited by the setting of standard clinical practice and by non-standardized endpoint determination. Observational studies can be more helpful moving research forward if they restrict focus to appropriate and valid endpoints. PMID:27354827

Cultivating cohort studies for observational translational research.

PubMed

Ransohoff, David F

2013-04-01

"Discovery" research about molecular markers for diagnosis, prognosis, or prediction of response to therapy has frequently produced results that were not reproducible in subsequent studies. What are the reasons, and can observational cohorts be cultivated to provide strong and reliable answers to those questions? Experimental Selected examples are used to illustrate: (i) what features of research design provide strength and reliability in observational studies about markers of diagnosis, prognosis, and response to therapy? (ii) How can those design features be cultivated in existing observational cohorts, for example, within randomized controlled clinical trial (RCT), other existing observational research studies, or practice settings like health maintenance organization (HMOs)? Examples include a study of RNA expression profiles of tumor tissue to predict prognosis of breast cancer, a study of serum proteomics profiles to diagnose ovarian cancer, and a study of stool-based DNA assays to screen for colon cancer. Strengths and weaknesses of observational study design features are discussed, along with lessons about how features that help assure strength might be "cultivated" in the future. By considering these examples and others, it may be possible to develop a process of "cultivating cohorts" in ongoing RCTs, observational cohort studies, and practice settings like HMOs that have strong features of study design. Such an effort could produce sources of data and specimens to reliably answer questions about the use of molecular markers in diagnosis, prognosis, and response to therapy.

Landscape of dietary factors associated with risk of gastric cancer: A systematic review and dose-response meta-analysis of prospective cohort studies.

PubMed

Fang, Xuexian; Wei, Jiayu; He, Xuyan; An, Peng; Wang, Hao; Jiang, Li; Shao, Dandan; Liang, Han; Li, Yi; Wang, Fudi; Min, Junxia

2015-12-01

The associations between dietary factors and gastric cancer risk have been analysed by many studies, but with inconclusive results. We conducted a meta-analysis of prospective studies to systematically investigate the associations. Relevant studies were identified through searching Medline, Embase, and Web of Science up to June 30, 2015. We included prospective cohort studies of intake of dietary factors with risk estimates and 95% confidence intervals for gastric cancer. Seventy-six prospective cohort studies were eligible and included in the analysis. We ascertained 32,758 gastric cancer cases out of 6,316,385 participants in relations to intake of 67 dietary factors, covering a wide ranging of vegetables, fruit, meat, fish, salt, alcohol, tea, coffee, and nutrients, during 3.3 to 30 years of follow-up. Evidence from this study indicates that consumption of total fruit and white vegetables, but not total vegetables, was inversely associated with gastric cancer risk. Both fruit and white vegetables are rich sources of vitamin C, which showed significant protective effect against gastric cancer by our analysis too. Furthermore, we found concordant positive associations between high-salt foods and gastric cancer risk. In addition, a strong effect of alcohol consumption, particularly beer and liquor but not wine, on gastric cancer risk was observed compared with nondrinkers. Dose-response analysis indicated that risk of gastric cancer was increased by 12% per 5 g/day increment of dietary salt intake or 5% per 10 g/day increment of alcohol consumption, and that a 100 g/day increment of fruit consumption was inversely associated with 5% reduction of risk. This study provides comprehensive and strong evidence that there are a number of protective and risk factors for gastric cancer in diet. Our findings may have significant public health implications with regard to prevention of gastric cancer and provide insights into future cohort studies and the design of related clinical trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Social and Emotional Characteristics and Early Childhood Mathematical and Literacy Giftedness: Observations From Parents and Childcare Providers Using the ECLS-B

ERIC Educational Resources Information Center

Wilson, Hope E.

2015-01-01

Research has demonstrated mixed results regarding differences in social and emotional characteristics between gifted and typical populations. The purpose of this secondary analysis of data from the Early Childhood Longitudinal Study: Birth Cohort (ECLS-B) is to investigate the affective characteristics of early mathematics and literacy ability…

Negative Control Outcomes and the Analysis of Standardized Mortality Ratios

PubMed Central

Richardson, DB; Keil, A; Tchetgen, Tchetgen E; Cooper, GS

2016-01-01

In occupational cohort mortality studies, epidemiologists often compare the observed number of deaths in the cohort to the expected number obtained by multiplying person-time accrued in the study cohort by the mortality rate in an external reference population. Interpretation of the result may be difficult due to non-comparability of the occupational cohort and reference population. We describe an approach to estimate an adjusted standardized mortality ratio (aSMR) to control for bias due to unmeasured differences between the occupational cohort and the reference population. The approach draws on methods developed for the use of negative control outcomes. Conditions necessary for unbiased estimation are described, as well as looser conditions necessary for bias reduction. The approach is illustrated using data on bladder cancer mortality among male Oak Ridge National Laboratory workers. The SMR for bladder cancer was elevated among hourly-paid males (SMR=1.90; 1.27, 2.72) but not among monthly-paid males (SMR=0.96; 0.67, 1.33). After indirect adjustment using the proposed approach, the mortality ratios were similar in magnitude among hourly- and monthly-paid men (aSMR=2.22; 1.52, 3.24; and, aSMR=1.99; 1.43, 2.76, respectively). The proposed adjusted SMR offers a complement to typical standardized mortality ratio analyses. PMID:26172862

Assessing the Genetic Predisposition of Education on Myopia: a Mendelian Randomization Study

PubMed Central

Cuellar-Partida, Gabriel; Lu, Yi; Kho, Pik Fang; Hewitt, Alex W.; Wichmann, H.-Erich; Yazar, Seyhan; Stambolian, Dwight; Bailey-Wilson, Joan E.; Wojciechowski, Robert; Wang, Jie Jin; Mitchell, Paul; Mackey, David A.; MacGregor, Stuart

2016-01-01

Myopia is the largest cause of uncorrected visual impairments globally and its recent dramatic increase in the population has made it a major public health problem. In observational studies, educational attainment has been consistently reported to be correlated to myopia. Nonetheless, correlation does not imply causation. Observational studies do not tell us if education causes myopia or if instead there are confounding factors underlying the association. In this work, we use a two-step least squares instrumental-variable (IV) approach to estimate the causal effect of education on refractive error, specifically myopia. We used the results from the educational attainment GWAS from the Social Science Genetic Association Consortium to define a polygenic risk score (PGRS) in three cohorts of late middle age and elderly Caucasian individuals (N=5,649). In a meta-analysis of the three cohorts, using the PGRS as an IV, we estimated that each z-score increase in education (approximately 2 years of education) results in a reduction of 0.92 ± 0.29 diopters (P=1.04×10−3). Our estimate of the effect of education on myopia was higher (P=0.01) than the observed estimate (0.25 ± 0.03 diopters reduction per education z-score [~2 years] increase). This suggests that observational studies may actually underestimate the true effect. Our Mendelian Randomization (MR) analysis provides new evidence for a causal role of educational attainment on refractive error. PMID:26497973

Assessing the Genetic Predisposition of Education on Myopia: A Mendelian Randomization Study.

PubMed

Cuellar-Partida, Gabriel; Lu, Yi; Kho, Pik Fang; Hewitt, Alex W; Wichmann, H-Erich; Yazar, Seyhan; Stambolian, Dwight; Bailey-Wilson, Joan E; Wojciechowski, Robert; Wang, Jie Jin; Mitchell, Paul; Mackey, David A; MacGregor, Stuart

2016-01-01

Myopia is the largest cause of uncorrected visual impairments globally and its recent dramatic increase in the population has made it a major public health problem. In observational studies, educational attainment has been consistently reported to be correlated to myopia. Nonetheless, correlation does not imply causation. Observational studies do not tell us if education causes myopia or if instead there are confounding factors underlying the association. In this work, we use a two-step least squares instrumental-variable (IV) approach to estimate the causal effect of education on refractive error, specifically myopia. We used the results from the educational attainment GWAS from the Social Science Genetic Association Consortium to define a polygenic risk score (PGRS) in three cohorts of late middle age and elderly Caucasian individuals (N = 5,649). In a meta-analysis of the three cohorts, using the PGRS as an IV, we estimated that each z-score increase in education (approximately 2 years of education) results in a reduction of 0.92 ± 0.29 diopters (P = 1.04 × 10(-3) ). Our estimate of the effect of education on myopia was higher (P = 0.01) than the observed estimate (0.25 ± 0.03 diopters reduction per education z-score [∼2 years] increase). This suggests that observational studies may actually underestimate the true effect. Our Mendelian Randomization (MR) analysis provides new evidence for a causal role of educational attainment on refractive error. © 2015 WILEY PERIODICALS, INC.

The Northern Norway mother-and-child contaminant cohort study: implementation, population characteristics and summary of dietary findings

PubMed Central

Veyhe, Anna Sofía; Hansen, Solrunn; Sandanger, Torkjel M.; Nieboer, Evert; Odland, Jon Øyvind

2012-01-01

Objectives To describe the essential features of a new Northern Norway mother-and-child contaminant cohort study called MISA, including its rationale, content, implementation and selected findings (mostly dietary). Study design Cross-sectional with longitudinal aspects. Methods Five hundred and fifteen eligible women were enrolled in early pregnancy, with 391 completing the study protocol that included a self-administrated food frequency questionnaire (FFQ) and donation of biological samples for contaminant analysis in the 2nd trimester, just after delivery, and 6 weeks postpartum. Macronutrient consumption was converted to energy intake, and the amounts of both macro- and micronutrients ingested were estimated. Some of the MISA findings were compared to data available in the Medical Birth Registry of Norway (MBRN). Results Compared to all 2004–2006 mothers in Northern Norway, the study cohort women were about 2 years older and smoked less; on average, they had close to 16 years of education. Parity, gestational age and birth weight of the newborn were comparable as well. The estimated average dietary intake of 8.1 MJ per day was less than that recommended by the Nordic Nutritional Recommendations (NNR), but the intake of micronutrients per MJ complied. Conclusions Although the final cohort sample size was less than targeted, the generally good comparisons observed between MBRN-registered information for the study cohort and dropouts suggest that this occurrence introduced minimal bias. The agreement of the observed demographic and clinical characteristics of the cohort women and newborns with all births in Northern Norway implied acceptable external validity. Also, the dietary findings aligned well with Norwegian national data and guidelines and other studies, as did the high prevalence of breastfeeding. The MISA database is considered suitable for exploring associations between contaminant exposure and diet, enhancing our knowledge of the interplay of the physiological changes that occur in mothers with contaminant pharmacokinetics (including transfer to the infant before and after birth), and conducting prospective health studies of the children. PMID:22957315

The Northern Norway mother-and-child contaminant cohort study: implementation, population characteristics and summary of dietary findings.

PubMed

Veyhe, Anna Sofía; Hansen, Solrunn; Sandanger, Torkjel M; Nieboer, Evert; Odland, Jon Øyvind

2012-01-01

To describe the essential features of a new Northern Norway mother-and-child contaminant cohort study called MISA, including its rationale, content, implementation and selected findings (mostly dietary). Cross-sectional with longitudinal aspects. Five hundred and fifteen eligible women were enrolled in early pregnancy, with 391 completing the study protocol that included a self-administrated food frequency questionnaire (FFQ) and donation of biological samples for contaminant analysis in the 2nd trimester, just after delivery, and 6 weeks postpartum. Macronutrient consumption was converted to energy intake, and the amounts of both macro- and micronutrients ingested were estimated. Some of the MISA findings were compared to data available in the Medical Birth Registry of Norway (MBRN). Compared to all 2004-2006 mothers in Northern Norway, the study cohort women were about 2 years older and smoked less; on average, they had close to 16 years of education. Parity, gestational age and birth weight of the newborn were comparable as well. The estimated average dietary intake of 8.1 MJ per day was less than that recommended by the Nordic Nutritional Recommendations (NNR), but the intake of micronutrients per MJ complied. Although the final cohort sample size was less than targeted, the generally good comparisons observed between MBRN-registered information for the study cohort and dropouts suggest that this occurrence introduced minimal bias. The agreement of the observed demographic and clinical characteristics of the cohort women and newborns with all births in Northern Norway implied acceptable external validity. Also, the dietary findings aligned well with Norwegian national data and guidelines and other studies, as did the high prevalence of breastfeeding. The MISA database is considered suitable for exploring associations between contaminant exposure and diet, enhancing our knowledge of the interplay of the physiological changes that occur in mothers with contaminant pharmacokinetics (including transfer to the infant before and after birth), and conducting prospective health studies of the children.

Increased risk of organic erectile dysfunction in patients with chronic fatigue syndrome: a nationwide population-based cohort study.

PubMed

Chao, C-H; Chen, H-J; Wang, H-Y; Li, T-C; Kao, C-H

2015-07-01

Chronic fatigue syndrome (CFS) is a complex disorder characterized by profound and persistent fatigue and several comorbidities. CFS was previously reported to be associated with female sexual dysfunction. We propose that CFS might also be associated with organic erectile dysfunction (organic ED). We conducted a retrospective cohort study by using data from the National Health Insurance (NHI) Research Database. We identified 2156 male patients who were newly diagnosed with CFS between January 1, 2003 and December 31, 2006. After excluding those younger than 20 years and prevalent cases, 1976 patients were subjected to analysis, and 7904 people served as healthy controls. All study subjects were followed up from the index date to the date of organic ED diagnosis, withdrawal from the NHI program, or the end of 2011. Compared with the non-CFS cohort, the incidence density rate of organic ED was 1.88-fold higher than that in the CFS cohort (3.23 vs. 1.73 per 1000 person-years) with an adjusted hazard ratio (HR) of 1.88 (95% CI = 1.26-2.81) when adjusting for sex and comorbidities. The combined impacts of patients with CFS and cardiovascular disease (CVD), diabetes mellitus (DM), chronic kidney disease (CKD), depression, and anxiety showed a significant by joint association with organic ED risk compared with patients with no CFS and no counterpart comorbidity. The greatest magnitude of adjusted HR of ED for CFS was observed in individuals without any comorbidity (3.87, 1.95-7.66). The incidence of organic ED is higher among males aged 40 years and over for both CFS and non-CFS cohorts. As the number of comorbidity increases, the incidence of organic ED increases in males without CFS. Higher incidence of organic ED was observed in males with CVD, DM, CKD, depression, or anxiety for both CFS and non-CFS cohorts. © 2015 American Society of Andrology and European Academy of Andrology.

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

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.

Liquid Biopsy Analysis of FGFR3 and PIK3CA Hotspot Mutations for Disease Surveillance in Bladder Cancer.

PubMed

Christensen, Emil; Birkenkamp-Demtröder, Karin; Nordentoft, Iver; Høyer, Søren; van der Keur, Kirstin; van Kessel, Kim; Zwarthoff, Ellen; Agerbæk, Mads; Ørntoft, Torben Falck; Jensen, Jørgen Bjerggaard; Dyrskjøt, Lars

2017-06-01

Disease surveillance in patients with bladder cancer is important for early diagnosis of progression and metastasis and for optimised treatment. To develop urine and plasma assays for disease surveillance for patients with FGFR3 and PIK3CA tumour mutations. Droplet digital polymerase chain reaction (ddPCR) assays were developed and tumour DNA from two patient cohorts was screened for FGFR3 and PIK3CA hotspot mutations. One cohort included 363 patients with non-muscle-invasive bladder cancer (NMIBC). The other cohort included 468 patients with bladder cancer undergoing radical cystectomy (Cx). Urine supernatants (NMIBC n=216, Cx n=27) and plasma samples (NMIBC n=39, Cx n=27) from patients harbouring mutations were subsequently screened using ddPCR assays. Progression-free survival, recurrence-free survival, and overall survival were measured. Fisher's exact test, the Wilcoxon rank-sum test and Cox regression analysis were applied. In total, 36% of the NMIBC patients (129/363) and 11% of the Cx patients (44/403) harboured at least one FGFR3 or PIK3CA mutation. Screening of DNA from serial urine supernatants from the NMIBC cohort revealed that high levels of tumour DNA (tDNA) were associated with later disease progression in NMIBC (p=0.003). Furthermore, high levels of tDNA in plasma samples were associated with recurrence in the Cx cohort (p=0.016). A positive correlation between tDNA levels in urine and plasma was observed (correlation coefficient 0.6). The retrospective study design and low volumes of plasma available for analysis were limitations of the study. Increased levels of FGFR3 and PIK3CA mutated DNA in urine and plasma are indicative of later progression and metastasis in bladder cancer. Urine and plasma from patients with bladder cancer may be monitored for diagnosis of progression and metastasis using mutation assays. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Age-period-cohort analysis of oral cancer mortality in Europe: the end of an epidemic?

PubMed

Bonifazi, Martina; Malvezzi, Matteo; Bertuccio, Paola; Edefonti, Valeria; Garavello, Werner; Levi, Fabio; La Vecchia, Carlo; Negri, Eva

2011-05-01

Over the last decade, mortality from oral and pharyngeal cancer has been declining in most European countries, but it had been increasing substantially in Hungary, Slovakia and a few other countries of central Europe, reaching rates comparable to those of lung cancer in several western European countries in males. To update trends in oral cancer mortality and further analyse the recent epidemic in central Europe, official death certifications for oral and pharyngeal cancer for 37 European countries were derived over the period 1970-2007, and an age-period-cohort model was fitted for selected countries. Male oral cancer mortality continued to decline in most European countries, including the Russian Federation, and, more importantly, it also started to decline in some of the countries with the highest male rates, i.e. Hungary and Slovakia; persisting rises were, however, observed in Belarus, Bulgaria and Romania. Oral cancer mortality rates for women were lower than in men and showed no appreciable trend over recent periods in the EU overall. Estimates from the age-period-cohort analysis for most selected countries showed a fall in effects for the cohorts born after the 1950s. For the period effect displayed a rise for the earlier periods, an inversion in the 1990 s and a continuous fall up to the last studied period. Only some former non-market economy countries, like Romania, Ukraine and Lithuania, had rising cohort effect trends up to most recent generations. The major finding of this updated analysis of oral cancer mortality is the leveling of the epidemic for men in most European countries, including Hungary and other central European countries, where mortality from this cancer was exceedingly high. These trends essentially reflect the changes in alcohol and tobacco consumption in various populations. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effects of chlorhexidine gluconate oral care on hospital mortality: a hospital-wide, observational cohort study.

PubMed

Deschepper, Mieke; Waegeman, Willem; Eeckloo, Kristof; Vogelaers, Dirk; Blot, Stijn

2018-05-09

Chlorhexidine oral care is widely used in critically and non-critically ill hospitalized patients to maintain oral health. We investigated the effect of chlorhexidine oral care on mortality in a general hospitalized population. In this single-center, retrospective, hospital-wide, observational cohort study we included adult hospitalized patients (2012-2014). Mortality associated with chlorhexidine oral care was assessed by logistic regression analysis. A threshold cumulative dose of 300 mg served as a dichotomic proxy for chlorhexidine exposure. We adjusted for demographics, diagnostic category, and risk of mortality expressed in four categories (minor, moderate, major, and extreme). The study cohort included 82,274 patients of which 11,133 (14%) received chlorhexidine oral care. Low-level exposure to chlorhexidine oral care (≤ 300 mg) was associated with increased risk of death [odds ratio (OR) 2.61; 95% confidence interval (CI) 2.32-2.92]. This association was stronger among patients with a lower risk of death: OR 5.50 (95% CI 4.51-6.71) with minor/moderate risk, OR 2.33 (95% CI 1.96-2.78) with a major risk, and a not significant OR 1.13 (95% CI 0.90-1.41) with an extreme risk of mortality. Similar observations were made for high-level exposure (> 300 mg). No harmful effect was observed in ventilated and non-ventilated ICU patients. Increased risk of death was observed in patients who did not receive mechanical ventilation and were not admitted to ICUs. The adjusted number of patients needed to be exposed to result in one additional fatality case was 47.1 (95% CI 45.2-49.1). These data argue against the indiscriminate widespread use of chlorhexidine oral care in hospitalized patients, in the absence of proven benefit in specific populations.

Nested Cohort - R software package

Cancer.gov

NestedCohort is an R software package for fitting Kaplan-Meier and Cox Models to estimate standardized survival and attributable risks for studies where covariates of interest are observed on only a sample of the cohort.

Steroidal contraceptives and bone fractures in women: evidence from observational studies.

PubMed

Lopez, Laureen M; Chen, Mario; Mullins Long, Sarah; Curtis, Kathryn M; Helmerhorst, Frans M

2015-07-21

Age-related decline in bone mass increases the risk of skeletal fractures, especially those of the hip, spine, and wrist. Steroidal contraceptives have been associated with changes in bone mineral density in women. Whether such changes affect the risk of fractures later in life is unclear. Hormonal contraceptives are among the most effective and most widely-used contraceptives. Concern about fractures may limit the use of these effective contraceptives. Observational studies can collect data on premenopausal contraceptive use as well as fracture incidence later in life. We systematically reviewed the evidence from observational studies of hormonal contraceptive use for contraception and the risk of fracture in women. Through June 2015, we searched for observational studies. The databases included PubMed, POPLINE, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, EMBASE, CINAHL, and Web of Science. We also searched for recent clinical trials through ClinicalTrials.gov and the ICTRP. For other studies, we examined reference lists of relevant articles and wrote to investigators for additional reports. We included cohort and case-control studies of hormonal contraceptive use. Interventions included comparisons of a hormonal contraceptive with a non-hormonal contraceptive, no contraceptive, or another hormonal contraceptive. The primary outcome was the risk of fracture. Two authors independently extracted the data. One author entered the data into RevMan, and a second author verified accuracy. We examined the quality of evidence using the Newcastle-Ottawa Quality Assessment Scale (NOS), developed for case-control and cohort studies. Sensitivity analysis included studies of moderate or high quality based on our assessment with the NOS.Given the need to control for confounding factors in observational studies, we used adjusted estimates from the models as reported by the authors. Where we did not have adjusted analyses, we calculated the odds ratio (OR) with 95% confidence interval (CI). Due to varied study designs, we did not conduct meta-analysis. We included 14 studies (7 case-control and 7 cohort studies). These examined oral contraceptives (OCs), depot medroxyprogesterone acetate (DMPA), and the hormonal intrauterine device (IUD). This section focuses on the sensitivity analysis with six studies that provided moderate or high quality evidence.All six studies examined oral contraceptive use. We noted few associations with fracture risk. One cohort study reported OC ever-users had increased risk for all fractures (RR 1.20, 95% CI 1.08 to 1.34). However, a case-control study with later data from a subset reported no association except for those with 10 years or more since use (OR 1.55, 95% CI 1.03 to 2.33). Another case-control study reported increased risk only for those who had 10 or more prescriptions (OR 1.09, 95% CI 1.03 to 1.16). A cohort study of postmenopausal women found no increased fracture risk for OC use after excluding women with prior fracture. Two other studies found little evidence of association between OC use and fracture risk. A cohort study noted increased risk for subgroups, such as those with longer use or specific intervals since use. A case-control study reported increased risk for any fracture only among young women with less than average use.Two case-control studies also examined progestin-only contraceptives. One reported increased fracture risk for DMPA ever-use (OR 1.44, 95% CI 1.01 to 2.06), more than four years of use (OR 2.16, 95% CI 1.32 to 3.53), and women over 50 years old. The other reported increased risk for any past use, including one or two prescriptions (OR 1.17, 95% CI 1.07 to 1.29) and for current use of 3 to 9 prescriptions (OR 1.36, 95% CI 1.15 to 1.60) or 10 or more (OR 1.54, 95% CI 1.33 to 1.78). For the levonorgestrel-releasing IUD, one study reported reduced fracture risk for ever-use (OR 0.75, 95% CI 0.64 to 0.87) and for longer use. Observational studies do not indicate an overall association between oral contraceptive use and fracture risk. Some reported increased risk for specific user subgroups. DMPA users may have an increased fracture risk. One study indicated hormonal IUD use may be associated with decreased risk. Observational studies need adjusted analysis because the comparison groups usually differ. Investigators should be clear about the variables examined in multivariate analysis.

[Mortality study of asbestos cement workers in Emilia-Romagna].

PubMed

Luberto, Ferdinando; Amendola, Plinio; Belli, Stefano; Bruno, Caterina; Candela, Silvia; Grignoli, Mario; Comba, Pietro

2004-01-01

The present study updates to 06/30/1998 the cohort mortality study of 3358 workers employed in 10 asbestos cement production plants in the Italian region Emilia-Romagna. The cohort includes 2712 males and 646 females. Overall mortality was significantly increased (SMR=131, IC95%:108-127). Excess mortality has been observed for all malignant neoplasms (SMR=131, IC95%: 115-149, 250 observed) and for respiratory diseases (SMR=153, IC: 105-216, 32 observed), 3 deaths due to asbestosis. Mortality for all respiratory tract neoplasms (SMR=179, IC: 148-215, 114 observed), pulmonary cancer (SMR=157, IC: 126-192, 90 observed) and pleural cancer (SMR=1922, IC: 1139-3038, 18 observed) are significantly increased. This study confirms the previous cohort study observation of increased mortality for all causes, all neoplasm and cancer affecting lungs and pleura.

Psychiatric disease incidence among Danish Seventh-day Adventists and Baptists.

PubMed

Thygesen, Lau Caspar; Dalton, Susanne Oksbjerg; Johansen, Christoffer; Ross, Lone; Kessing, Lars Vedel; Hvidt, Niels Christian

2013-10-01

Previous studies suggest that religious practice can have a positive effect on mental health, but may also have potential for harm. In Denmark, unique possibilities are available for studying the influence of religious practice on mental health: Denmark is characterized as a secular society and it is possible to follow members of religious societies in nationwide registers. In this study, we follow a cohort of Danish Seventh-day Adventists (SDA) and Baptists in a nationwide psychiatry register and compare the incidence in this cohort with the general population. We followed a cohort of 5,614 SDA and 3,663 Baptists in the Danish Psychiatric Central Register, which contained information on psychiatric hospitalizations from 1970 to 2009. Psychiatric disease incidence in the cohort was compared with that in the general Danish population as standardized incidence ratios and within-cohort comparisons were made with a Cox model. The cohort had decreased incidence of abuse disorders compared to the general population. Furthermore, among Baptists, decreased incidence of unipolar disorders among men and decreased incidence of schizophrenia among women were observed. Surprisingly, we observed an increased incidence rate of unipolar disorder among women. In this nationwide cohort study with 40 years of follow-up, we observed increased incidence rates of unipolar disorders among women and decreased rates of alcohol- and drug-related psychiatric disorders compared to the general Danish population. We have no mechanistic explanation for the increased incidence of unipolar disorders among women, but discuss several hypotheses that could explain this observation.

Maternal Smoking in Pregnancy and Offspring Depression: a cross cohort and negative control study.

PubMed

Taylor, Amy E; Carslake, David; de Mola, Christian Loret; Rydell, Mina; Nilsen, Tom I L; Bjørngaard, Johan H; Horta, Bernardo Lessa; Pearson, Rebecca; Rai, Dheeraj; Galanti, Maria Rosaria; Barros, Fernando C; Romundstad, Pål R; Davey Smith, George; Munafò, Marcus R

2017-10-03

Previous reports suggest that offspring of mothers who smoke during pregnancy have greater risk of developing depression. However, it is unclear whether this is due to intrauterine effects. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) from the UK (N = 2,869), the Nord-Trøndelag health study (HUNT) from Norway (N = 15,493), the Pelotas 1982 Birth Cohort Study from Brazil (N = 2,626), and the Swedish Sibling Health Cohort (N = 258 sibling pairs), we compared associations of maternal smoking during pregnancy and mother's partner's smoking during pregnancy with offspring depression and performed a discordant sibling analysis. In meta-analysis, maternal smoking during pregnancy was associated with higher odds of offspring depression (OR 1.20, 95% CI:1.08,1.34), but mother's partner's smoking during pregnancy was not (OR 1.05, 95% CI:0.94,1.17). However, there was only weak statistical evidence that the odds ratios for maternal and mother's partner's smoking differed from each other (p = 0.08). There was no clear evidence for an association between maternal smoking during pregnancy and offspring depression in the sibling analysis. Findings do not provide strong support for a causal role of maternal smoking during pregnancy in offspring depression, rather observed associations may reflect residual confounding relating to characteristics of parents who smoke.

Genetic analysis of dyslexia candidate genes in the European cross-linguistic NeuroDys cohort.

PubMed

Becker, Jessica; Czamara, Darina; Scerri, Tom S; Ramus, Franck; Csépe, Valéria; Talcott, Joel B; Stein, John; Morris, Andrew; Ludwig, Kerstin U; Hoffmann, Per; Honbolygó, Ferenc; Tóth, Dénes; Fauchereau, Fabien; Bogliotti, Caroline; Iannuzzi, Stéphanie; Chaix, Yves; Valdois, Sylviane; Billard, Catherine; George, Florence; Soares-Boucaud, Isabelle; Gérard, Christophe-Loïc; van der Mark, Sanne; Schulz, Enrico; Vaessen, Anniek; Maurer, Urs; Lohvansuu, Kaisa; Lyytinen, Heikki; Zucchelli, Marco; Brandeis, Daniel; Blomert, Leo; Leppänen, Paavo H T; Bruder, Jennifer; Monaco, Anthony P; Müller-Myhsok, Bertram; Kere, Juha; Landerl, Karin; Nöthen, Markus M; Schulte-Körne, Gerd; Paracchini, Silvia; Peyrard-Janvid, Myriam; Schumacher, Johannes

2014-05-01

Dyslexia is one of the most common childhood disorders with a prevalence of around 5-10% in school-age children. Although an important genetic component is known to have a role in the aetiology of dyslexia, we are far from understanding the molecular mechanisms leading to the disorder. Several candidate genes have been implicated in dyslexia, including DYX1C1, DCDC2, KIAA0319, and the MRPL19/C2ORF3 locus, each with reports of both positive and no replications. We generated a European cross-linguistic sample of school-age children - the NeuroDys cohort - that includes more than 900 individuals with dyslexia, sampled with homogenous inclusion criteria across eight European countries, and a comparable number of controls. Here, we describe association analysis of the dyslexia candidate genes/locus in the NeuroDys cohort. We performed both case-control and quantitative association analyses of single markers and haplotypes previously reported to be dyslexia-associated. Although we observed association signals in samples from single countries, we did not find any marker or haplotype that was significantly associated with either case-control status or quantitative measurements of word-reading or spelling in the meta-analysis of all eight countries combined. Like in other neurocognitive disorders, our findings underline the need for larger sample sizes to validate possibly weak genetic effects.

Impact of operation details on hydrocephalus after decompressive craniectomy

PubMed Central

Wang, Qiang-Ping; Ma, Jun-Peng; Zhou, Zhang-Ming; You, Chao

2016-01-01

Objective: To evaluate the correlation between the distance of craniectomy from the midline and hydrocephalus after DC. Methods: The following electronic databases were searched from their inception to June 2015: Cochrane Library, MEDLINE, Science Direct, EMBASE, Scopus, Google Scholar, the Chinese Biomedical Database (CBM), and the Chinese National Knowledge Infrastructure (CNKI). All randomized clinical trials, prospective cohort, retrospective observational cohort, and case-control studies investigating the relationship between distance of craniectomy from the midline and hydrocephalus after DC were enrolled. The Cochrane Collaboration’s software RevMan 5.3 was used for meta-analysis. Results: Six retrospective cohort studies involving 462 participants were included. Pooled analysis of 4 studies suggested that craniectomy close to the midline (<25 mm) was associated with a significantly increased risk of postoperative hydrocephalus (odds ratio [OR] = 3.61, 95% confidence interval [CI]: 1.3 - 9.97, p=0.01). However, meta-analysis of 4 studies did not find statistical differences when comparing the distance of craniectomy from the midline in the hydrocephalus group and that in the non-hydrocephalus group (OR = −0.14, 95% CI: −0.44 - 0.15, p=0.34). Conclusions: Available evidence was insufficient to support the theory that craniectomy close to the midline increases the risk of developing hydrocephalus after DC. Well-conducted randomized clinical trials are required to verify this issue. PMID:26818161

Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada: collaborative cohort analysis.

PubMed

2016-01-28

To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure. Collaborative analysis of data from eight European and three Canadian cohorts. Adults (N>20 000) who started triple ART between 1996 and 2012 and had data on viral subtype were followed for mortality. We estimated crude and adjusted (for age, sex, regimen, CD4 cell count, and AIDS at baseline, period of starting ART, stratified by cohort, region of origin and risk group) mortality hazard ratios (MHR) by subtype. We estimated MHR subsequent to viral failure defined as two HIV-RNA measurements greater than 500 copies/ml after achieving viral suppression. The most prevalent subtypes were B (15 419; 74%), C (2091; 10%), CRF02AG (1057; 5%), A (873; 4%), CRF01AE (506; 2.4%), G (359; 1.7%), and D (232; 1.1%). Subtypes were strongly patterned by region of origin and risk group. During 104 649 person-years of observation, 1172/20 784 patients died. Compared with subtype B, mortality was higher for subtype A, but similar for all other subtypes. MHR for A versus B were 1.13 (95% confidence interval 0.85,1.50) when stratified by cohort, increased to 1.78 (1.27,2.51) on stratification by region and risk, and attenuated to 1.59 (1.14,2.23) on adjustment for covariates. MHR for A versus B was 2.65 (1.64,4.28) and 0.95 (0.57,1.57) for patients who started ART with CD4 cell count below, or more than, 100 cells/μl, respectively. There was no difference in mortality between subtypes A, B and C after viral failure. Patients with subtype A had worse prognosis, an observation which may be confounded by socio-demographic factors.

A tale of two countries: all-cause mortality among people living with HIV and receiving combination antiretroviral therapy in the UK and Canada.

PubMed

Patterson, S; Jose, S; Samji, H; Cescon, A; Ding, E; Zhu, J; Anderson, J; Burchell, A N; Cooper, C; Hill, T; Hull, M; Klein, M B; Loutfy, M; Martin, F; Machouf, N; Montaner, Jsg; Nelson, M; Raboud, J; Rourke, S B; Tsoukas, C; Hogg, R S; Sabin, C

2017-10-01

We sought to compare all-cause mortality of people living with HIV and accessing care in Canada and the UK. Individuals from the Canadian Observational Cohort (CANOC) collaboration and UK Collaborative HIV Cohort (UK CHIC) study who were aged ≥ 18 years, had initiated antiretroviral therapy (ART) for the first time between 2000 and 2012 and who had acquired HIV through sexual transmission were included in the analysis. Cox regression was used to investigate the difference in mortality risk between the two cohort collaborations, accounting for loss to follow-up as a competing risk. A total of 19 960 participants were included in the analysis (CANOC, 4137; UK CHIC, 15 823). CANOC participants were more likely to be older [median age 39 years (interquartile range (IQR): 33, 46 years) vs. 36 years (IQR: 31, 43 years) for UK CHIC participants], to be male (86 vs. 73%, respectively), and to report men who have sex with men (MSM) sexual transmission risk (72 vs. 56%, respectively) (all P < 0.001). Overall, 762 deaths occurred during 98 798 person-years (PY) of follow-up, giving a crude mortality rate of 7.7 per 1000 PY [95% confidence interval (CI): 7.1, 8.3 per 1000 PY]. The crude mortality rates were 8.6 (95% CI: 7.4, 10.0) and 7.5 (95% CI: 6.9, 8.1) per 1000 PY among CANOC and UK CHIC study participants, respectively. No statistically significant difference in mortality risk was observed between the cohort collaborations in Cox regression accounting for loss to follow-up as a competing risk (adjusted hazard ratio 0.86; 95% CI: 0.72-1.03). Despite differences in national HIV care provision and treatment guidelines, mortality risk did not differ between CANOC and UK CHIC study participants who acquired HIV through sexual transmission. © 2017 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

Dynamics on networks: the role of local dynamics and global networks on the emergence of hypersynchronous neural activity.

PubMed

Schmidt, Helmut; Petkov, George; Richardson, Mark P; Terry, John R

2014-11-01

Graph theory has evolved into a useful tool for studying complex brain networks inferred from a variety of measures of neural activity, including fMRI, DTI, MEG and EEG. In the study of neurological disorders, recent work has discovered differences in the structure of graphs inferred from patient and control cohorts. However, most of these studies pursue a purely observational approach; identifying correlations between properties of graphs and the cohort which they describe, without consideration of the underlying mechanisms. To move beyond this necessitates the development of computational modeling approaches to appropriately interpret network interactions and the alterations in brain dynamics they permit, which in the field of complexity sciences is known as dynamics on networks. In this study we describe the development and application of this framework using modular networks of Kuramoto oscillators. We use this framework to understand functional networks inferred from resting state EEG recordings of a cohort of 35 adults with heterogeneous idiopathic generalized epilepsies and 40 healthy adult controls. Taking emergent synchrony across the global network as a proxy for seizures, our study finds that the critical strength of coupling required to synchronize the global network is significantly decreased for the epilepsy cohort for functional networks inferred from both theta (3-6 Hz) and low-alpha (6-9 Hz) bands. We further identify left frontal regions as a potential driver of seizure activity within these networks. We also explore the ability of our method to identify individuals with epilepsy, observing up to 80% predictive power through use of receiver operating characteristic analysis. Collectively these findings demonstrate that a computer model based analysis of routine clinical EEG provides significant additional information beyond standard clinical interpretation, which should ultimately enable a more appropriate mechanistic stratification of people with epilepsy leading to improved diagnostics and therapeutics.

On the use and misuse of scalar scores of confounders in design and analysis of observational studies.

PubMed

Pfeiffer, R M; Riedl, R

2015-08-15

We assess the asymptotic bias of estimates of exposure effects conditional on covariates when summary scores of confounders, instead of the confounders themselves, are used to analyze observational data. First, we study regression models for cohort data that are adjusted for summary scores. Second, we derive the asymptotic bias for case-control studies when cases and controls are matched on a summary score, and then analyzed either using conditional logistic regression or by unconditional logistic regression adjusted for the summary score. Two scores, the propensity score (PS) and the disease risk score (DRS) are studied in detail. For cohort analysis, when regression models are adjusted for the PS, the estimated conditional treatment effect is unbiased only for linear models, or at the null for non-linear models. Adjustment of cohort data for DRS yields unbiased estimates only for linear regression; all other estimates of exposure effects are biased. Matching cases and controls on DRS and analyzing them using conditional logistic regression yields unbiased estimates of exposure effect, whereas adjusting for the DRS in unconditional logistic regression yields biased estimates, even under the null hypothesis of no association. Matching cases and controls on the PS yield unbiased estimates only under the null for both conditional and unconditional logistic regression, adjusted for the PS. We study the bias for various confounding scenarios and compare our asymptotic results with those from simulations with limited sample sizes. To create realistic correlations among multiple confounders, we also based simulations on a real dataset. Copyright © 2015 John Wiley & Sons, Ltd.

Prospective observational cohort studies for studying rare diseases: the European PedNet Haemophilia Registry.

PubMed

Fischer, K; Ljung, R; Platokouki, H; Liesner, R; Claeyssens, S; Smink, E; van den Berg, H M

2014-07-01

Haemophilia is a rare disease. To improve knowledge, prospective studies of large numbers of subjects are needed. To establish a large well-documented birth cohort of patients with haemophilia enabling studies on early presentation, side effects and outcome of treatment. Twenty-one haemophilia treatment centres have been collecting data on all children with haemophilia with FVIII/IX levels up to 25% born from 2000 onwards. Another eight centres collected data on severe haemophilia A only. At baseline, details on delivery and diagnosis, gene mutation, family history of haemophilia and inhibitors are collected. For the first 75 exposure days, date, reason, dose and product are recorded for each infusion. Clinically relevant inhibitors are defined as follows: at least two positive inhibitor titres and a FVIII/IX recovery <66% of expected. For inhibitor patients, results of all inhibitor- and recovery tests are collected. For continued treatment, data on bleeding, surgery, prophylaxis and clotting factor consumption are collected annually. Data are downloaded for analysis annually. In May 2013, a total of 1094 patients were included: 701 with severe, 146 with moderate and 247 with mild haemophilia. Gene defect data were available for 87.6% of patients with severe haemophilia A. The first analysis, performed in May 2011, lead to two landmark publications. The outcome of this large collaborative research confirms its value for the improvement of haemophilia care. High-quality prospective observational cohorts form an ideal source to study natural history and treatment in rare diseases such as haemophilia. © 2014 John Wiley & Sons Ltd.

What could we learn from the sub-analysis of a single nation cohort in a worldwide study? Lessons from the results observed in the Italian cohort of the GO-MORE trial.

PubMed

Giacomelli, Roberto; Ruscitti, Piero; Bombardieri, Stefano; Cuomo, Giovanna; De Vita, Salvatore; Galeazzi, Mauro; Mecchia, Monica

2017-01-01

GO-MORE Trial investigated the use of Golimumab (GLM) in 3280 rheumatoid arthritis (RA) patients worldwide. At present, the burden of arthritis is greater in poorer countries than in developed countries due to socioeconomic disparities, thus suggesting the usefulness of subgroup investigations. We aimed to evaluate GLM as add-on therapy for RA patients in the Italian cohort of GO-MORE trial and compared the clinical characteristics between Italian patients and the enrolled patients worldwide. Ninety-eight Italian patients with active RA, fulfilling the 1987 ACR criteria were enrolled. Statistical analyses were performed to assess: i. the differences in baseline characteristics; ii. the efficacy after 6 months; between Italian and Rest of the World GO-MORE populations. Compared to the worldwide population, Italian patients showed a lower value of disease activity and a significantly short disease duration. Unlike the worldwide patients, the large majority of Italian patients received biologic therapy after the failure of the first synthetic DMARD and were not treated by high methotrexate dosage. After 6 months of GLM treatment, no differences were observed in the therapeutic response. Italian patients reported a positive autoinjection experience mirroring the worldwide results. The analysis of the Italian GO-MORE subset confirms that differences among patients may be shown, depending on different approaches in different health systems. GLM in the Italian patients showed a favourable benefit/risk profile and the positive autoinjection experience may help with patient's compliance and survival of the treatment.

Genetic Variation in SENP1 and ANP32D as Predictors of Chronic Mountain Sickness

PubMed Central

Petousi, Nayia; Cavalleri, Gianpiero L.; Robbins, Peter A.

2014-01-01

Abstract Cole, Amy M., Nayia Petousi, Gianpiero L. Cavalleri, and Peter A. Robbins Genetic variation in SENP1 and ANP32D as predictors of chronic mountain sickness. High Alt Med Biol 15:497–499, 2014.—Chronic mountain sickness (CMS) is a serious illness that affects life-long high-altitude residents. A recent study analyzed whole genome sequence data from residents of Cerro de Pasco (Peru) in an effort to identify the genetic basis of CMS and reported SENP1 (rs7963934) and ANP32D (rs72644851) to show signatures consistent with natural selection and protective against CMS (Zhou et al. 2013). We set out to replicate these observations in two Andean cohorts from Cerro de Pasco, consisting of 84 CMS cases and 91 healthy controls in total. We report evidence of association for rs7963934 (SENP1) in the combined cohorts (meta-analysis p=8.8 x 10−4 OR 2.91, CI 1.56–5.5, I=0). The direction of effect was the same as in the original publication. We did not observe any significant correlation between rs72644851 (ANP32D) and the CMS phenotype, within or across cohorts (meta-analysis p=0.204, OR 1.37, CI 0.84–2.241, I=0). Our results provide independent evidence in support of a role for SENP1 in CMS in individuals of Quechua ancestry and suggest the SENP1 and ANP32D signatures of selection are in tight linkage disequilibrium (LD). PMID:25225945

Safety of Temporary Discontinuation of Antihypertensive Medication in Patients With Difficult-to-Control Hypertension.

PubMed

Beeftink, Martine M A; van der Sande, Nicolette G C; Bots, Michiel L; Doevendans, Pieter A; Blankestijn, Peter J; Visseren, Frank L J; Voskuil, Michiel; Spiering, Wilko

2017-05-01

Successful control of blood pressure relies on identification of secondary causes and contributing factors of hypertension. As antihypertensive medication can interfere with diagnostic investigations, temporary discontinuation of medication is advised. However, there are concerns about the safety of temporary discontinuation of antihypertensive medication in patients with difficult-to-control hypertension. We assessed the occurrence of adverse cardiovascular and cerebrovascular events potentially attributable to temporary discontinuation of antihypertensive medication between February 2010 and March 2016 (n=604) in our Analysis of Complicated Hypertension screening program. A reference group (n=604) was extracted from the SMART study (Second Manifestations of Arterial Disease) cohort (comprising a similar cohort at our hospital in whom medication was not stopped) and individually matched for blood pressure, age, sex, and history of cardiovascular disease. Discontinuation of medication was well tolerated; 62% reported no complaints, 24% had mild discomfort that could be left untreated, and 14% experienced complaints that required prescription of antihypertensive escape medication. Three major adverse events were observed in the Analysis of Complicated Hypertension group between discontinuation of medication and 30 days after restart of medication (event rate=31.2 events per 1000 patient-year). In the reference cohort, 5 cardiovascular events were observed during a similar follow-up period (event rate=51.2 events per 1000 patient-year). In conclusion, discontinuation of antihypertensive medication for the diagnostic evaluation of hypertension does not increase the acute risk of cardiovascular events when performed in a well-controlled setting in specialized hospitals with appropriate protocols for monitoring safety. © 2017 American Heart Association, Inc.

Can commonly prescribed drugs be repurposed for the prevention or treatment of Alzheimer's and other neurodegenerative diseases? Protocol for an observational cohort study in the UK Clinical Practice Research Datalink

PubMed Central

Davies, Neil M; Jones, Tim; Kehoe, Patrick G; Martin, Richard M

2016-01-01

Introduction Current treatments for Alzheimer's and other neurodegenerative diseases have only limited effectiveness meaning that there is an urgent need for new medications that could influence disease incidence and progression. We will investigate the potential of a selection of commonly prescribed drugs, as a more efficient and cost-effective method of identifying new drugs for the prevention or treatment of Alzheimer's disease, non-Alzheimer's disease dementias, Parkinson's disease and amyotrophic lateral sclerosis. Our research will focus on drugs used for the treatment of hypertension, hypercholesterolaemia and type 2 diabetes, all of which have previously been identified as potentially cerebroprotective and have variable levels of preclinical evidence that suggest they may have beneficial effects for various aspects of dementia pathology. Methods and analysis We will conduct a hypothesis testing observational cohort study using data from the Clinical Practice Research Datalink (CPRD). Our analysis will consider four statistical methods, which have different approaches for modelling confounding. These are multivariable adjusted Cox regression; propensity matched regression; instrumental variable analysis and marginal structural models. We will also use an intention-to-treat analysis, whereby we will define all exposures based on the first prescription observed in the database so that the target parameter is comparable to that estimated by a randomised controlled trial. Ethics and dissemination This protocol has been approved by the CPRD's Independent Scientific Advisory Committee (ISAC). We will publish the results of the study as open-access peer-reviewed publications and disseminate findings through national and international conferences as are appropriate. PMID:27965247

Cancer mortality in a northern Italian cohort of rubber workers.

PubMed

Negri, E; Piolatto, G; Pira, E; Decarli, A; Kaldor, J; La Vecchia, C

1989-09-01

An analysis of the mortality of a cohort of 6629 workers employed from 1906 to 1981 in a rubber tyre factory in northern Italy (978 deaths and over 133,000 man-years at risk) showed that the all cause mortality ratio was slightly lower than expected (0.91). Overall cancer mortality was close to expected (275 v 259.4) but there were significant excess rates for two cancer sites: pleura (9 observed v 0.8 expected, which may be due to the use of fibre containing talc) and bladder (16 observed v 8.8 expected). Death rates were not raised for other sites previously associated with employment in the rubber industry, such as cancers of the lung and brain, leukaemias, or lymphomas. The substantially reduced relative risk of pleural cancer among workers first employed after 1940 (RR = 0.05 compared with before 1940) probably reflected improvements in working conditions over more recent periods. For cancer of the bladder, the relative risk was also lower for workers first engaged after 1940. Thus no appreciable risk for any disease was apparent for workers employed over the past four decades. Analysis for each of the 27 job categories showed a substantial excess for cancer of the pleura in the mechanical maintenance workers (4 observed v 0.17 expected); an excess of cancer of the lung (21 v 13.48) was also present in this job category.

Cancer mortality in a northern Italian cohort of rubber workers.

PubMed Central

Negri, E; Piolatto, G; Pira, E; Decarli, A; Kaldor, J; La Vecchia, C

1989-01-01

An analysis of the mortality of a cohort of 6629 workers employed from 1906 to 1981 in a rubber tyre factory in northern Italy (978 deaths and over 133,000 man-years at risk) showed that the all cause mortality ratio was slightly lower than expected (0.91). Overall cancer mortality was close to expected (275 v 259.4) but there were significant excess rates for two cancer sites: pleura (9 observed v 0.8 expected, which may be due to the use of fibre containing talc) and bladder (16 observed v 8.8 expected). Death rates were not raised for other sites previously associated with employment in the rubber industry, such as cancers of the lung and brain, leukaemias, or lymphomas. The substantially reduced relative risk of pleural cancer among workers first employed after 1940 (RR = 0.05 compared with before 1940) probably reflected improvements in working conditions over more recent periods. For cancer of the bladder, the relative risk was also lower for workers first engaged after 1940. Thus no appreciable risk for any disease was apparent for workers employed over the past four decades. Analysis for each of the 27 job categories showed a substantial excess for cancer of the pleura in the mechanical maintenance workers (4 observed v 0.17 expected); an excess of cancer of the lung (21 v 13.48) was also present in this job category. PMID:2789965

Cancer-related Imaging in the Veterans Affairs Health Care System versus Medicare: Does a System with Lower Use Exhibit Less Geographic Variation?

PubMed Central

McWilliams, J. Michael; Dalton, Jesse B.; Landrum, Mary Beth; Frakt, Austin B.; Pizer, Steven D.; Keating, Nancy L.

2014-01-01

Background Geographic variations in use of medical services have been interpreted as indirect evidence of wasteful care. Less overuse of services, however, may not be reliably associated with less geographic variation. Objective To compare average use and geographic variation in use of cancer-related imaging between fee-for-service Medicare and the Department of Veterans Affairs (VA) health care system. Design Observational analysis of cancer-related imaging from 2003–2005, using Medicare and VA utilization data linked to cancer registry data. We used multilevel models to estimate mean differences in annual imaging use between cohorts of Medicare and VA patients within geographic areas and variation in use across areas for each cohort, adjusting for sociodemographic and tumor characteristics. Setting 40 hospital referral regions. Patients Older men with lung, colorectal, or prostate cancer, including 34,475 traditional Medicare beneficiaries (Medicare cohort) and 6,835 VA patients (VA cohort). Measurements 1)Per-patient count of imaging studies for which lung, colorectal, or prostate cancer was the primary diagnosis (each study weighted by a standardized price); 2)a direct measure of overuse—advanced imaging for prostate cancer at low risk of metastasis. Results Adjusted annual use of cancer-related imaging was lower in the VA cohort than the Medicare cohort (price-weighted count, $197 vs. $379/patient; P<0.001), as was annual use of advanced imaging for prostate cancer at low risk of metastasis ($41 vs. $117/patient; P<0.001). Geographic variation in cancer-related imaging use was similar in magnitude in the VA and Medicare cohorts. Limitations Observational study design. Conclusions Use of cancer-related imaging was lower in the VA health care system than in fee-for-service Medicare, but lower use was not associated with less geographic variation. Geographic variation in service use may not be a reliable indicator of the extent of overuse. Primary Funding Source Doris Duke Charitable Foundation and Department of Veterans Affairs Office of Policy and Planning. PMID:25437407

Suicide Mortality Among Retired National Football League Players Who Played 5 or More Seasons

PubMed Central

Lehman, Everett J.; Hein, Misty J.; Gersic, Christine M.

2016-01-01

Background There is current disagreement in the scientific literature about the relationship between playing football and suicide risk, particularly among professional players in the National Football League (NFL). While some research indicates players are at high risk of football-related concussions, which may lead to chronic traumatic encephalopathy and suicide, other research finds such a connection to be speculative and unsupported by methodologically sound research. Purpose To compare the suicide mortality of a cohort of NFL players to what would be expected in the general population of the United States. Study Design Cohort study; Level of evidence, 3. Methods A cohort of 3439 NFL players with at least 5 credited playing seasons between 1959 and 1988 was assembled for statistical analysis. The vital status for this cohort was updated through 2013. Standardized mortality ratios (SMRs), the ratio of observed deaths to expected deaths, and 95% CIs were computed for the cohort; 95% CIs that excluded unity were considered statistically significant. For internal comparison purposes, standardized rate ratios were calculated to compare mortality results between players stratified into speed and nonspeed position types. Results Suicide among this cohort of professional football players was significantly less than would be expected in comparison with the United States population (SMR = 0.47; 95% CI, 0.24–0.82). There were no significant differences in suicide mortality between speed and nonspeed position players. Conclusion There is no indication of elevated suicide risk in this cohort of professional football players with 5 or more credited seasons of play. Because of the unique nature of this cohort, these study results may not be applicable to professional football players who played fewer than 5 years or to college or high school players. PMID:27159317

Replication of association of DENND1A and THADA variants with polycystic ovary syndrome in European cohorts.

PubMed

Goodarzi, Mark O; Jones, Michelle R; Li, Xiaohui; Chua, Angela K; Garcia, Obed A; Chen, Yii-Der I; Krauss, Ronald M; Rotter, Jerome I; Ankener, Wendy; Legro, Richard S; Azziz, Ricardo; Strauss, Jerome F; Dunaif, Andrea; Urbanek, Margrit

2012-02-01

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with a strong familial component. PCOS is characterised by hyperandrogenaemia and irregular menses. A recent genome-wide association study (GWAS) of PCOS in a Chinese cohort identified three reproducible PCOS susceptibility loci mapping to 2p16.3 (luteinising hormone/choriogonadotropin receptor; LHCGR), 2p21 (thyroid associated protein; THADA), and 9q33.3 (DENN/MADD domain containing 1A; DENNDIA). The impact of these loci in non-Chinese PCOS cohorts remains to be determined. The study tested association with PCOS of seven single nucleotide polymorphisms mapping to the three Chinese PCOS loci in two European derived PCOS cohorts (cohort A = 939 cases and 957 controls; cohort B = 535 cases and 845 controls). Cases fulfilled the National Institute of Child Health & Human Development criteria for PCOS. Variation in DENND1A was strongly associated with PCOS in the study cohort (p(combined cohorts)=10(-8)); multiple variants in THADA were also associated with PCOS, while there was no significant evidence for association of LHCGR variation with PCOS. The present study had >80% power to detect an effect of similar size as was observed by Chen et al for DENND1A and THADA, but reduced power (at <40%) for LHCGR at p=0.0001. The study had sufficient power (57-88%) for LHCGR at p=0.01. At least two of the PCOS susceptibility loci identified in the Chinese PCOS GWAS (DENND1A and THADA) are also associated with PCOS in European derived populations, and are therefore likely to be important in the aetiology of PCOS regardless of ethnicity. The analysis of the LHCGR gene was not sufficiently powered to detect modest effects.

Suicide Mortality Among Retired National Football League Players Who Played 5 or More Seasons.

PubMed

Lehman, Everett J; Hein, Misty J; Gersic, Christine M

2016-10-01

There is current disagreement in the scientific literature about the relationship between playing football and suicide risk, particularly among professional players in the National Football League (NFL). While some research indicates players are at high risk of football-related concussions, which may lead to chronic traumatic encephalopathy and suicide, other research finds such a connection to be speculative and unsupported by methodologically sound research. To compare the suicide mortality of a cohort of NFL players to what would be expected in the general population of the United States. Cohort study; Level of evidence, 3. A cohort of 3439 NFL players with at least 5 credited playing seasons between 1959 and 1988 was assembled for statistical analysis. The vital status for this cohort was updated through 2013. Standardized mortality ratios (SMRs), the ratio of observed deaths to expected deaths, and 95% CIs were computed for the cohort; 95% CIs that excluded unity were considered statistically significant. For internal comparison purposes, standardized rate ratios were calculated to compare mortality results between players stratified into speed and nonspeed position types. Suicide among this cohort of professional football players was significantly less than would be expected in comparison with the United States population (SMR = 0.47; 95% CI, 0.24-0.82). There were no significant differences in suicide mortality between speed and nonspeed position players. There is no indication of elevated suicide risk in this cohort of professional football players with 5 or more credited seasons of play. Because of the unique nature of this cohort, these study results may not be applicable to professional football players who played fewer than 5 years or to college or high school players. © 2016 The Author(s).

Comparative hazards of acute myocardial infarction among hospitalized patients with methamphetamine- or cocaine-use disorders: A retrospective cohort study.

PubMed

Callaghan, Russell C; Halliday, Montana; Gatley, Jodi; Sykes, Jenna; Taylor, Lawren; Benny, Claire; Kish, Stephen J

2018-07-01

It is assumed that recreational use of methamphetamine can trigger acute myocardial infarction (AMI) events, but estimates of longitudinal hazards of AMI among methamphetamine users are lacking. Retrospective cohort study: Competing-risks analysis was used to estimate time-to-AMI patterns in methamphetamine versus matched appendicitis (population-proxy) and matched cocaine (drug-control) groups. Cohorts were propensity-score-matched using demographic and clinical variables. California, 1990-2005. Cohorts of individuals with no prior or concurrent history of AMI hospitalized with methamphetamine- (n = 73,056), cocaine- (n = 47,726), or appendicitis-related conditions (n = 330,109). ICD-9/ICD-10 indications of AMI (ICD-9 410.X; ICD-10 I21.X) in death records or inpatient hospital data. Patients in methamphetamine cohort were more likely to develop subsequent AMI in comparison to those in matched appendicitis cohort [Hazard ratio (HR): 1.41; 95% CI, 1.23-1.62, p < 0.0001], with increased risk most marked in young methamphetamine users (age 15-34 years; HR: 2.04; 95% CI, 1.63-2.57, p = 0. 0001). Risk was slightly increased vs. that in matched cocaine group (HR: 1.19; 95% CI, 1.02-1.39, p = 0. 029). Individuals in cocaine cohort were also more likely to experience AMI outcome vs. appendicitis cohort (HR: 1.25; 95% CI, 1.08-1.45, p = 0. 0023). Our longitudinal data support results of earlier epidemiological studies suggesting that persons with methamphetamine- (or cocaine-) use disorders might have increased AMI risk. However, because of potential study limitations and the unexpectedly modest magnitude of the observed increased AMI hazard, these findings must be considered preliminary and require replication. Copyright © 2018. Published by Elsevier B.V.

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

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.

Breast feeding and intergenerational social mobility: what are the mechanisms?

PubMed Central

Sacker, A; Kelly, Y; Iacovou, M; Cable, N; Bartley, M

2013-01-01

Objective To investigate the association between breast feeding and intergenerational social mobility and the possible mediating role of neurological and stress mechanisms. Design Secondary analysis of data from the 1958 and the 1970 British Cohort Studies. Setting Longitudinal study of individuals born in Britain during 1 week in 1958 and 1970. Participants 17 419 individuals participated in the 1958 cohort and 16 771 in the 1970 cohort. The effect of breast feeding on intergenerational social mobility from age 10/11 to age 33/34 was analysed after multiple imputations to fill in missing data and propensity score matching on a wide range of confounders measured in childhood (1958 cohort N=16 039–16 154; 1970 cohort N=16 255–16 361). Main outcome measures Own Registrar General's Social Class (RGSC) at 33/34 years adjusted for father's RGSC at 10/11 years, gender and their interaction. Results Breastfed individuals were more likely to be upwardly mobile (1958 cohort: OR 1.24 95% CI 1.12 to 1.38; 1970 cohort: OR 1.24 95% CI 1.12 to 1.37) and less likely to be downwardly mobile (1958 cohort: OR 0.81 95% CI 0.73 to 0.90; 1970 cohort: OR 0.79 95% CI 0.71 to 0.88). In an ordinal regression model, markers of neurological development (cognitive test scores) and stress (emotional stress scores) accounted for approximately 36% of the relationship between breast feeding and social mobility. Conclusions Breast feeding increased the odds of upward social mobility and decreased the odds of downward mobility. Consistent with a causal explanation, the findings were robust to matching on a large number of observable variables and effect sizes were alike for two cohorts with different social distributions of breast feeding. The effect was mediated in part through neurological and stress mechanisms. PMID:23798701

Multidimensional severity assessment in bronchiectasis: an analysis of seven European cohorts

PubMed Central

McDonnell, M J; Aliberti, S; Goeminne, P C; Dimakou, K; Zucchetti, S C; Davidson, J; Ward, C; Laffey, J G; Finch, S; Pesci, A; Dupont, L J; Fardon, T C; Skrbic, D; Obradovic, D; Cowman, S; Loebinger, M R; Rutherford, R M; De Soyza, A; Chalmers, J D

2016-01-01

Introduction Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality. Methods We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies. Results The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in ‘severe’ patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline. Conclusion The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity. PMID:27516225

External validation and clinical utility of a prediction model for 6-month mortality in patients undergoing hemodialysis for end-stage kidney disease.

PubMed

Forzley, Brian; Er, Lee; Chiu, Helen Hl; Djurdjev, Ognjenka; Martinusen, Dan; Carson, Rachel C; Hargrove, Gaylene; Levin, Adeera; Karim, Mohamud

2018-02-01

End-stage kidney disease is associated with poor prognosis. Health care professionals must be prepared to address end-of-life issues and identify those at high risk for dying. A 6-month mortality prediction model for patients on dialysis derived in the United States is used but has not been externally validated. We aimed to assess the external validity and clinical utility in an independent cohort in Canada. We examined the performance of the published 6-month mortality prediction model, using discrimination, calibration, and decision curve analyses. Data were derived from a cohort of 374 prevalent dialysis patients in two regions of British Columbia, Canada, which included serum albumin, age, peripheral vascular disease, dementia, and answers to the "the surprise question" ("Would I be surprised if this patient died within the next year?"). The observed mortality in the validation cohort was 11.5% at 6 months. The prediction model had reasonable discrimination (c-stat = 0.70) but poor calibration (calibration-in-the-large = -0.53 (95% confidence interval: -0.88, -0.18); calibration slope = 0.57 (95% confidence interval: 0.31, 0.83)) in our data. Decision curve analysis showed the model only has added value in guiding clinical decision in a small range of threshold probabilities: 8%-20%. Despite reasonable discrimination, the prediction model has poor calibration in this external study cohort; thus, it may have limited clinical utility in settings outside of where it was derived. Decision curve analysis clarifies limitations in clinical utility not apparent by receiver operating characteristic curve analysis. This study highlights the importance of external validation of prediction models prior to routine use in clinical practice.

[Malignant tumor incidence in employees of the Alytus textile factory (1978-1997)].

PubMed

Kuzmickiene, Irena; Stukonis, Mecys; Didziapetris, Remigijus

2002-01-01

The purpose of this study was to evaluate cancer incidence in the large cotton-manufacturing factory in Lithuania. Altogether 10,198 workers employed at least 1 year in 1969-1997 were included in the cohort and followed during the period 1978/01/01-1997/12/31. National cancer rates were used to calculate the expected number of cancer cases. The overall cancer risk for men was slightly higher than that in the general population (standardized incidence rate (SIR) 1.15, 95% confidence interval (95% CI) 0.98-1.34). A significant increase in the incidence of esophagus (11 observed cases, SIR 3.76, 95% CI 1.88-6.67) and slightly increased of lung (42 observed cases, SIR 1.26, 95% CI 0.91-1.70) cancer became evident. None of the cancer risk showed statistically significant excess cancer incidence in the textile-processing (spinning and weaving) departments (SIR 0.98). In the women cohort the level of the general incidence was very close to expected, standardized incidence rates (SIR) being 0.99 (95% CI 0.88-1.13). However, there was a significant increase in the number of cases of gall bladder (6 observed, SIR 3.19, 95% CI 1.17-6.95). The analysis of the results among textile-processing (spinning and weaving departments) workers indicated the elevated risk of breast cancer (44 observed cases, SIR 1.49, 95% CI 1.08-2.0) and cervical cancer (24 observed cases, SIR 1.68, 95% CI 1.08-2.50). The number of lung cancer cases in this group was a higher, but statistically not significant (5 observed cases, SIR 1.53, 95% CI 0.5-3.58). Increased SIR values were observed for > or = 10 years since the first exposure for all cancers, cervix uteri, ovary and kidney. The overall cancer risk for men cohort was slightly higher than that in the general population. There was a significant increase in the number of cancer of the esophagus. The overall excess risk in women cohort was only for gall bladder, but for spinners and weavers the elevated risk was for cervix uteri and breast cancer. After 10 years of employment the excess risk was already for all cancers, cervix uteri, ovary and kidney malignant tumors.

International testicular cancer incidence trends: generational transitions in 38 countries 1900-1990.

PubMed

Znaor, Ariana; Lortet-Tieulent, Joannie; Laversanne, Mathieu; Jemal, Ahmedin; Bray, Freddie

2015-01-01

Rapid increases in testicular cancer incidence have marked the second half of the last century. While these secular rises, observed mainly in countries attaining the highest levels of human development, appear to have attenuated in the last decade, rates continue to increase in countries transiting toward high developmental levels. The purpose of our study was to provide a comprehensive analysis and presentation of the cohort-specific trends in testicular cancer incidence rates in 38 countries worldwide. We used an augmented version of the Cancer Incidence in Five Continents series to analyze testicular cancer incidence in men aged 15-54 in 38 countries, via age-period-cohort analysis. In many European countries, the USA, Canada, Australia, and New Zealand, there is a continuation of the increasing risk among successive generations, yet rates are attenuating in male cohorts born since the 1970s in several Northern European countries, in contrast to the steeply increasing trends in recent cohorts in Southern Europe. Incidence rates have also been increasing in the populations traditionally at rather low risk, such as in the Philippines, Singapore, China, and Costa Rica. The attenuation of testicular cancer risk in younger generations (in the most developed countries) alongside concomitant increases (in countries undergoing developmental change) is indicative of a global transition in the risk of testicular cancer. While identifying the underlying causes remains a major challenge, increasing awareness and adapting national healthcare systems to accommodate a growing burden of testicular cancer may prevent future avoidable deaths in young men.

Olive oil in the prevention and management of type 2 diabetes mellitus: a systematic review and meta-analysis of cohort studies and intervention trials.

PubMed

Schwingshackl, L; Lampousi, A-M; Portillo, M P; Romaguera, D; Hoffmann, G; Boeing, H

2017-04-10

Olive oil (OO) as food is composed mainly of fatty acids and bioactive compounds depending from the extraction method. Both had been discussed as health promoting with still open questions. Thus, we conducted a meta-analysis to illustrate the impact of this food on type 2 diabetes (T2D) by investigating the association between OO intake and risk of T2D, and the effect of OO intake in the management of T2D. Searches were performed in PubMed, Cochrane Library and google scholar. First, we conducted a random effect meta-analysis of prospective cohort studies and trials investigating the association between OO and risk of T2D. Second, a meta-analysis was performed to detect the effects of olive oil on glycemic control in patients with T2D. Four cohort studies including 15 784 T2D cases and 29 trials were included in the meta-analysis. The highest OO intake category showed a 16% reduced risk of T2D (RR: 0.84; 95% CI: 0.77, 0.92) compared with the lowest. However, we observed evidence for a nonlinear relationship. In T2D patients OO supplementation resulted in a significantly more pronounced reduction in HbA1c (MD: -0.27%; 95% CI: -0.37, -0.17) and fasting plasma glucose (MD: -0.44 mmol l -1 ; 95% CI -0.66, -0.22) as compared with the control groups. This meta-analysis provides evidence that the intake of OO could be beneficial for the prevention and management of T2D. This conclusion regards OO as food, and might not been valid for single components comprising this food.

Assessing Health Outcomes After Environmental Exposures Associated With Open Pit Burning in Deployed US Service Members.

PubMed

Rohrbeck, Patricia; Hu, Zheng; Mallon, Col Timothy M

2016-08-01

This study assessed the long-term health impact of environmental exposures associated with open pit burning in deployed US service members. Two hundred individuals deployed to Balad, Iraq, and Bagram, Afghanistan, with known exposure to open pits, were matched to 200 non-deployed service members. Both cohorts were observed for adverse health outcomes after returning from deployment. Slight increased risks were observed for respiratory diseases in the Bagram cohort (adj RR: 1.259), and for cardiovascular disease in the Balad cohort (adj RR: 1.072), but the findings were not significant. The combined deployed cohort showed lower risks for adverse health outcomes, suggesting a healthy deployer effect. In conclusion, this study did not find significantly increased risks for selected health outcomes after burn pit exposure during deployment among two deployed cohorts compared with a non-deployed cohort.

Program evaluation of remote heart failure monitoring: healthcare utilization analysis in a rural regional medical center.

PubMed

Riley, William T; Keberlein, Pamela; Sorenson, Gigi; Mohler, Sailor; Tye, Blake; Ramirez, A Susana; Carroll, Mark

2015-03-01

Remote monitoring for heart failure (HF) has had mixed and heterogeneous effects across studies, necessitating further evaluation of remote monitoring systems within specific healthcare systems and their patient populations. "Care Beyond Walls and Wires," a wireless remote monitoring program to facilitate patient and care team co-management of HF patients, served by a rural regional medical center, provided the opportunity to evaluate the effects of this program on healthcare utilization. Fifty HF patients admitted to Flagstaff Medical Center (Flagstaff, AZ) participated in the project. Many of these patients lived in underserved and rural communities, including Native American reservations. Enrolled patients received mobile, broadband-enabled remote monitoring devices. A matched cohort was identified for comparison. HF patients enrolled in this program showed substantial and statistically significant reductions in healthcare utilization during the 6 months following enrollment, and these reductions were significantly greater compared with those who declined to participate but not when compared with a matched cohort. The findings from this project indicate that a remote HF monitoring program can be successfully implemented in a rural, underserved area. Reductions in healthcare utilization were observed among program participants, but reductions were also observed among a matched cohort, illustrating the need for rigorous assessment of the effects of HF remote monitoring programs in healthcare systems.

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

Is dietary nitrate/nitrite exposure a risk factor for development of thyroid abnormality? A systematic review and meta-analysis.

PubMed

Bahadoran, Zahra; Mirmiran, Parvin; Ghasemi, Asghar; Kabir, Ali; Azizi, Fereidoun; Hadaegh, Farzad

2015-05-01

The potential effects of inorganic nitrate/nitrite on global health are a much debated issue. In addition to possible methemoglobinemia and carcinogenic properties, anti-thyroid effects of nitrate/nitrite have been suggested. Considering the growing significance of nitrate/nitrite and since there is no comprehensive review in data available, clarifying the effect of nitrate/nitrite on thyroid disorder outcomes is essential. Therefore, we conducted this systematic review of experimental and clinical studies, and a meta-analysis of relevant cohort and cross-sectional studies investigating the association of nitrate/nitrite exposure and thyroid function. Most animal studies show that high exposure (~10-600 times of acceptable daily intake) to nitrate/nitrite induces anti-thyroid effects, including decreased serum level of thyroid hormones and histomorphological changes in thyroid gland; however no similar observations have been documented in humans. Based on our meta-analysis, no significant association was observed between nitrate exposure and the risk of thyroid cancer, hyper- and hypothyroidism; findings from three cohort studies however showed a significant association between higher exposure to nitrite and the risk of thyroid cancer (risk = 1.48, 95% confidence interval = 1.09-2.02, P = 0.012). Additional research is needed to clarify the association between nitrate/nitrite exposures and both thyroid function and cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections.

PubMed

Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

2015-01-01

Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1-4), rhinovirus, adenovirus (A-F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011-2013. The results were corroborated in an independent cohort collected in the UK. A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12-24 months age group. The most frequently observed co-infection patterns were RSV-Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV-bocavirus / bocavirus-influenza (5 patients, 5.2%, UK cohort). The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12-24 months of age. The clinical significance of these findings is unclear but should warrant further analysis.

Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections

PubMed Central

Cebey-López, Miriam; Herberg, Jethro; Pardo-Seco, Jacobo; Gómez-Carballa, Alberto; Martinón-Torres, Nazareth; Salas, Antonio; Martinón-Sánchez, José María; Gormley, Stuart; Sumner, Edward; Fink, Colin; Martinón-Torres, Federico

2015-01-01

Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis. PMID:26332375

Genetic Obesity and the Risk of Atrial Fibrillation – Causal Estimates from Mendelian Randomization

PubMed Central

Chatterjee, Neal A.; Arking, Dan E.; Ellinor, Patrick T.; Heeringa, Jan; Lin, Honghuang; Lubitz, Steven A.; Soliman, Elsayed Z.; Verweij, Niek; Alonso, Alvaro; Benjamin, Emelia J.; Gudnason, Vilmundur; Stricker, Bruno H. C.; Van Der Harst, Pim; Chasman, Daniel I.; Albert, Christine M.

2017-01-01

Background Observational studies have identified an association between body mass index (BMI) and incident atrial fibrillation (AF). Inferring causality from observational studies, however, is subject to residual confounding, reverse causation, and bias. The primary objective of this study was to evaluate the causal association between BMI and AF using genetic predictors of BMI. Methods We identified 51 646 individuals of European ancestry without AF at baseline from seven prospective population-based cohorts initiated between 1987 and 2002 in the United States, Iceland, and the Netherlands with incident AF ascertained between 1987 and 2012. Cohort-specific mean follow-up ranged 7.4 to 19.2 years, over which period there were a total of 4178 cases of incident AF. We performed a Mendelian randomization with instrumental variable analysis to estimate a cohort-specific causal hazard ratio for the association between BMI and AF. Two genetic instruments for BMI were utilized: FTO genotype (rs1558902) and a BMI gene score comprised of 39 single nucleotide polymorphisms identified by genome-wide association studies to be associated with BMI. Cohort-specific estimates were combined by random-effects, inverse variance weighted meta-analysis. Results In age- and sex-adjusted meta-analysis, both genetic instruments were significantly associated with BMI (FTO: 0.43 [95% CI: 0.32 – 0.54] kg/m2 per A-allele, p<0.001); BMI gene score: 1.05 [95% CI: 0.90-1.20] kg/m2 per 1 unit increase, p<0.001) and incident AF (FTO – HR: 1.07 [1.02-1.11] per A-allele, p=0.004; BMI gene score – HR: 1.11 [1.05-1.18] per 1-unit increase, p<0.001). Age- and sex-adjusted instrumental variable estimates for the causal association between BMI and incident AF were HR 1.15 [1.04-1.26] per kg/m2, p=0.005 (FTO) and 1.11 [1.05-1.17] per kg/m2, p<0.001 (BMI gene score). Both of these estimates were consistent with the meta-analyzed estimate between observed BMI and AF (age- and sex-adjusted HR 1.05 [1.04-1.06] per kg/m2, p<0.001). Multivariable adjustment did not significantly change findings. Conclusions Our data are consistent with a causal relationship between BMI and incident AF. These data support the possibility that public health initiatives targeting primordial prevention of obesity may reduce the incidence of AF. PMID:27974350

Cancer Mortality through 2005 among a Pooled Cohort of U.S. Nuclear Workers Exposed to External Ionizing Radiation.

PubMed

Schubauer-Berigan, Mary K; Daniels, Robert D; Bertke, Stephen J; Tseng, Chih-Yu; Richardson, David B

2015-06-01

Nuclear workers worldwide have been studied for decades to estimate associations between their exposure to ionizing radiation and cancer. The low-level exposure of these workers requires pooling of large cohorts studied over many years to obtain risk estimates with appropriate latency and good precision. We assembled a pooled cohort of 119,195 U.S. nuclear workers at four Department of Energy nuclear weapons facilities (Hanford site, Idaho National Laboratory, Oak Ridge National Laboratory and Savannah River site) and at the Portsmouth Naval Shipyard. The cohort was followed at the start of the workers beginning their radiation work (at earliest, between 1944 and 1952) through 2005, and we compared its mortality to that of the U.S. We also conducted regression-modeling analysis to evaluate dose-response associations for external radiation exposure and outcomes: all cancers, smoking- and nonsmoking-related cancers, all lymphatic and hematopoietic cancers, leukemia (excluding chronic lymphocytic), multiple myeloma, cardiovascular disease and others. The mean dose observed among the cohort was 20 mSv. For most outcomes, mortality was below expectation compared to the general population, but mesothelioma and pleura cancers were highly elevated. We found an excess relative risk (ERR) per 10 mSv of 0.14% [95% confidence interval (CI): -0.17%, 0.48%] for all cancers excluding leukemia. Estimates were higher for nonsmoking-related cancers (0.70%, 95% CI: 0.058%, 1.5%) and lower for smoking-related cancers (-0.079%, 95% CI: -0.43%, 0.32%). The ERR per 10 mSv was 1.7% (95% CI: -0.22%, 4.7%) for leukemia, which was similar to the estimate of 1.8% (95% CI: 0.027%, 4.4%) for all lymphatic and hematopoietic cancers. The ERR per 10 mSv for multiple myeloma was 3.9% (95% CI: 0.60%, 9.5%). The ERR per 10 mSv for cardiovascular disease was 0.026% (-0.25%, 0.32%). Little evidence of heterogeneity was seen by facility, birth cohort or sex for most outcomes. The estimates observed here are similar to those found in previous large pooled nuclear worker studies and also (with the exception of multiple myeloma) to those conducted in the Life Span Study of Japanese atomic bomb survivors. The tendency of observed risks to persist many years after exposure for most outcomes illustrates the importance of continued follow-up of nuclear worker cohorts.

Proton-pump inhibitors use, and risk of acute kidney injury: a meta-analysis of observational studies.

PubMed

Yang, Yi; George, Kaisha C; Shang, Wei-Feng; Zeng, Rui; Ge, Shu-Wang; Xu, Gang

2017-01-01

Recent studies have suggested a potential increased risk of acute kidney injury (AKI) among proton-pump inhibitor (PPI) users. However, the present results are conflicting. Thus, we performed a meta-analysis to investigate the association between PPI therapy and the risk of AKI. EMBASE, PubMed, Web of Science, and Cochrane Library databases (up to September 23, 2016) were systematically searched for any studies assessing the relationship between PPI use and risk of AKI. Studies that reported relevant risk ratios (RRs), odds ratios, or hazard ratios were included. We calculated the pooled RRs with 95% confidence intervals (CI) using a random-effects model of the meta-analysis. Subgroup analysis was conducted to explore the source of heterogeneity. Seven observational studies (five cohort studies and two case-control studies) were identified and included, and a total of 513,696 cases of PPI use among 2,404,236 participants were included in the meta-analysis. The pooled adjusted RR of AKI in patients with PPIs use was 1.61 (95% CI: 1.16-2.22; I 2 =98.1%). Furthermore, higher risks of AKI were found in the subgroups of cohort studies, participant's average age <60 years, participants with and without baseline PPI excluded, sample size <300,000, and number of adjustments ≥11. Subgroup analyses revealed that participants with or without baseline PPI excluded might be a source of heterogeneity. PPI use could be a risk factor for AKI and should be administered carefully. Nevertheless, some confounding factors might impact the outcomes. More well-designed prospective studies are needed to clarify the association.

Breast implants and the risk of breast cancer: a meta-analysis of cohort studies.

PubMed

Noels, Eline C; Lapid, Oren; Lindeman, Jan H N; Bastiaannet, Esther

2015-01-01

The popularity of cosmetic breast augmentation and the incidence of breast cancer have been increasing worldwide. It has been hypothesized that the risk of breast cancer may be greater among patients who have undergone cosmetic breast implantation. The authors performed a meta-analysis of the available literature on the risk of breast cancer among women with cosmetic breast implants. The study was designed as a meta-analysis of observational studies. A systematic search of the English literature (published by August 28, 2013) was conducted in PubMed and EMBASE. Eligible reports were those that included relative risk (RR; the increased or decreased risk of breast cancer associated with breast implants) or the standardized incidence ratio (SIR) of the observed number of cases of breast cancer to the expected number of cases among patients that previously underwent cosmetic breast augmentation. Seventeen studies representing 7 cohorts were selected. Some of these were follow-up reports of previously published studies; in such cases, only the most recent reports were included in the meta-analysis. Summary SIR and RR rates and the corresponding 95% confidence intervals (CIs) were calculated with a random-effects (SIR) or fixed-effects (RR) model. The overall SIR estimate was 0.69 (95% CI, 0.56-0.85), and the overall RR, based on 4 studies, was 0.63 (95% CI, 0.56-0.71). Finding of this meta-analysis suggest that women who have undergone cosmetic breast implantation do not have an increased risk of breast cancer. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.

PubMed

Sabatti, Chiara; Service, Susan K; Hartikainen, Anna-Liisa; Pouta, Anneli; Ripatti, Samuli; Brodsky, Jae; Jones, Chris G; Zaitlen, Noah A; Varilo, Teppo; Kaakinen, Marika; Sovio, Ulla; Ruokonen, Aimo; Laitinen, Jaana; Jakkula, Eveliina; Coin, Lachlan; Hoggart, Clive; Collins, Andrew; Turunen, Hannu; Gabriel, Stacey; Elliot, Paul; McCarthy, Mark I; Daly, Mark J; Järvelin, Marjo-Riitta; Freimer, Nelson B; Peltonen, Leena

2009-01-01

Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.

Hypoglycaemia with oral antidiabetic drugs: results from prescription-event monitoring cohorts of rosiglitazone, pioglitazone, nateglinide and repaglinide.

PubMed

Vlckova, Veronika; Cornelius, Victoria; Kasliwal, Rachna; Wilton, Lynda; Shakir, Saad A W

2009-01-01

Hypoglycaemia is an acute complication associated with intensive treatment of patients with diabetes mellitus. This complication poses a major challenge in diabetes management. Furthermore, severe hypoglycaemia may be life threatening. Although hypoglycaemia is more often associated with insulin treatment, oral hypoglycaemic agents have the potential to trigger hypoglycaemia. The aim of this study was to quantify the incidence of hypoglycaemic events and to describe the pattern of these incident events during the first 9 months of treatment with four oral antidiabetic drugs, rosiglitazone, pioglitazone, nateglinide and repaglinide, prescribed in general practice in England. We used data collected for prescription-event monitoring (PEM) studies of rosiglitazone, pioglitazone, nateglinide and repaglinide. PEM is an observational, non-interventional, incept cohort study. Observation time for each patient and incidence rate (IR) per 1000 patient-years of treatment for hypoglycaemia was calculated for each drug cohort. Smoothed hazard estimates were plotted over time. Case/non-case analysis was performed to describe and compare patients who had at least one hypoglycaemic event in the first 9 months of treatment with those who did not. The total number of patients included in the analysis was 14,373, 12,768, 4,549 and 5,727 in rosiglitazone, pioglitazone, nateglinide and repaglinide cohorts, respectively. From these, 276 patients experienced at least one episode of hypoglycaemia. The IR was between 50% and 100% higher in patients receiving treatment with meglitinides compared with those treated with the thiazolidinediones (TZDs) [IR = 9.94, 9.64, 15.71 and 20.32 per 1,000 patient-years for rosiglitazone, pioglitazone, nateglinide and repaglinide, respectively]. The plot of the hazard function and the estimated shape parameter from the Weibull regression model showed that pioglitazone, nateglinide and repaglinide had non-constant (decreasing) hazards over time, whereas the hazard for rosiglitazone-treated patients was approximately constant over time. Nateglinide and repaglinide had similar shape hazard function, indicating a significantly higher number of hypoglycaemic episodes shortly after starting treatment. For women treated with TZDs, hypoglycaemia was reported more frequently than for men. This analysis shows that the frequency of reported hypoglycaemia within the study cohorts was relatively low. The rates of hypoglycaemia were not equal between drug classes. Treatment with nateglinide or repaglinide was characterized by a higher incidence of hypoglycaemia at the beginning of treatment. Further investigation is necessary to assess whether women treated with TZDs are more prone to hypoglycaemia than men. Findings from this study should be taken into account with other clinical and pharmacoepidemiological studies.

Comparative Analysis of Anterior Chamber Flare Grading between Clinicians with Different Levels of Experience and Semi-automated Laser Flare Photometry.

PubMed

Agrawal, Rupesh; Keane, Pearse A; Singh, Jasmin; Saihan, Zubin; Kontos, Andreas; Pavesio, Carlos E

2016-01-01

To assess correlation for anterior chamber flare grading between clinicians with different levels of experience and with semi-automated flare reading in a cohort of patients with heterogeneous uveitic entities. Fifty-nine observations from 36 patients were recorded and analyzed for statistical association. In each patient, flare was assessed objectively using the Kowa FM-700 laser flare photometer, and subjective masked grading by two clinicians was performed. The study demonstrated disparity in flare readings between clinical graders with one step disagreement in clinical grading in 26 (44.06%) eyes (p < 0.001) and concordance between the flare readings by experienced grader and flare photometry. After review of semi-automated flare readings, management was changed in 11% of the patients. Laser flare photometry can be a valuable tool to remove the observer bias in grading flare for selected cohort of uveitis patients. It can be further applied to titrate therapy in intraocular inflammation.

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.

Flavopiridol Can Be Safely Administered Using a Pharmacologically Derived Schedule and Demonstrates Activity in Relapsed and Refractory Non-Hodgkin’s Lymphoma

PubMed Central

Jones, Jeffrey A.; Rupert, Amy S.; Poi, Ming; Phelps, Mitch A.; Andritsos, Leslie; Baiocchi, Robert; Benson, Don M.; Blum, Kristie A.; Christian, Beth; Flynn, Joseph; Penza, Sam; Porcu, Pierluigi; Grever, Michael R.; Byrd, John C.

2014-01-01

Flavopiridol is a broad cyclin-dependent kinase inhibitor (CDKI) that induces apoptosis of malignant lymphocytes in vitro and in murine lymphoma models. We conducted a phase I dose-escalation study to determine the maximum tolerated dose (MTD) for single-agent flavopiridol administered on a pharmacokinetically derived hybrid dosing schedule to patients with relapsed and refractory non-Hodgkin’s lymphoma. Dose was escalated independently in one of four cohorts: indolent B-cell (cohort 1), mantle cell (cohort 2), intermediate grade B-cell including transformed lymphoma (cohort 3), and T-/NK-cell excluding primary cutaneous disease (cohort 4). Forty-six patients were accrued. Grade 3 or 4 leukopenia was observed in the majority of patients (60%), but infection was infrequent. Common non-hematologic toxicties included diarrhea and fatigue. Biochemical tumor lysis was observed in only 2 patients, and no patients required hemodialysis for its management. Dose escalation was completed in two cohorts (indolent and aggressive B-cell). Dose-limiting toxicities were not observed, and the MTD was not reached in either cohort at the highest dose tested (50 mg/m2 bolus + 50 mg/m2 continuous infusion weekly for 4 consecutive weeks of a 6 week cycle). Clinical benefit was observed in 26% of 43 patients evaluable for response, including 14% with partial responses (2 mantle cell, 3 indolent B-cell, and 1 diffuse large B-cell). The single-agent activity of this first-generation CDKI suggests that other agents in this class merit further study in lymphoid malignancies, both alone and in combination. PMID:23959599

Clinical Research Methodology 2: Observational Clinical Research.

PubMed

Sessler, Daniel I; Imrey, Peter B

2015-10-01

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

Mortality analysis by neighbourhood in a city with high levels of industrial air pollution.

PubMed

Vigotti, Maria Angela; Mataloni, Francesca; Bruni, Antonella; Minniti, Caterina; Gianicolo, Emilio A L

2014-08-01

Taranto, a city in south-eastern Italy, suffers serious environmental pollution from industrial sources. A previous cohort analysis found mortality excesses among neighbourhoods closest to industrial areas. Aim of this study was to investigate whether mortality also increased in other neighbourhoods compared to Apulia region. Standardized mortality ratios were computed. Number of deaths and of person-years at risk by neighbourhood came from the previous cohort study for 1998-2008 period. Reference population was Apulia region excluding Taranto province. A meta-analysis was conducted across less close neighbourhoods computing summary SMR estimates and evaluating heterogeneity. For the entire city higher mortality values are confirmed for all causes, all malignant neoplasms and several specific sites, neurological, cardiac, respiratory and digestive diseases. High mortality values are not confined to neighbourhoods closest to industrial areas for lung cancer, cardiac, respiratory and digestive diseases, in both sexes, and among women for all malignant neoplasms and pancreatic cancer. Increased mortality risks can also be observed in Taranto neighbourhoods not directly adjacent to industrial areas. Spatial trend, impact of socio-economic factors and duration of residence should be further explored.

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.

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.

Comparative analysis of primary versus relapse/refractory DLBCL identifies shifts in mutation spectrum.

PubMed

Greenawalt, Danielle M; Liang, Winnie S; Saif, Sakina; Johnson, Justin; Todorov, Petar; Dulak, Austin; Enriquez, Daniel; Halperin, Rebecca; Ahmed, Ambar; Saveliev, Vladislav; Carpten, John; Craig, David; Barrett, J Carl; Dougherty, Brian; Zinda, Michael; Fawell, Stephen; Dry, Jonathan R; Byth, Kate

2017-11-21

Current understanding of the mutation spectrum of relapsed/refractory (RR) tumors is limited. We performed whole exome sequencing (WES) on 47 diffuse large B cell lymphoma (DLBCL) tumors that persisted after R-CHOP treatment, 8 matched to primary biopsies. We compared genomic alterations from the RR cohort against two treatment-naïve DLBCL cohorts (n=112). While the overall number and types of mutations did not differ significantly, we identified frequency changes in DLBCL driver genes. The overall frequency of MYD88 mutant samples increased (12% to 19%), but we noted a decrease in p.L265P (8% to 4%) and increase in p.S219C mutations (2% to 6%). CARD11 p.D230N, PIM1 p.K115N and CD79B p.Y196C mutations were not observed in the RR cohort, although these mutations were prominent in the primary DLBCL samples. We observed an increase in BCL2 mutations (21% to 38% of samples), BCL2 amplifications (3% to 6% of samples) and CREBBP mutations (31% to 42% of samples) in the RR cohort, supported by acquisition of mutations in these genes in relapsed compared to diagnostic biopsies from the same patient. These increases may reflect the genetic characteristics of R-CHOP RR tumors expected to be enriched for during clinical trial enrollment. These findings hold significance for a number of emerging targeted therapies aligned to genetic targets and biomarkers in DLBCL, reinforcing the importance of time-of-treatment biomarker screening during DLBCL therapy selection.

Comparative analysis of primary versus relapse/refractory DLBCL identifies shifts in mutation spectrum

PubMed Central

Greenawalt, Danielle M.; Liang, Winnie S.; Saif, Sakina; Johnson, Justin; Todorov, Petar; Dulak, Austin; Enriquez, Daniel; Halperin, Rebecca; Ahmed, Ambar; Saveliev, Vladislav; Carpten, John; Craig, David; Barrett, J. Carl; Dougherty, Brian; Zinda, Michael; Fawell, Stephen; Dry, Jonathan R.; Byth, Kate

2017-01-01

Current understanding of the mutation spectrum of relapsed/refractory (RR) tumors is limited. We performed whole exome sequencing (WES) on 47 diffuse large B cell lymphoma (DLBCL) tumors that persisted after R-CHOP treatment, 8 matched to primary biopsies. We compared genomic alterations from the RR cohort against two treatment-naïve DLBCL cohorts (n=112). While the overall number and types of mutations did not differ significantly, we identified frequency changes in DLBCL driver genes. The overall frequency of MYD88 mutant samples increased (12% to 19%), but we noted a decrease in p.L265P (8% to 4%) and increase in p.S219C mutations (2% to 6%). CARD11 p.D230N, PIM1 p.K115N and CD79B p.Y196C mutations were not observed in the RR cohort, although these mutations were prominent in the primary DLBCL samples. We observed an increase in BCL2 mutations (21% to 38% of samples), BCL2 amplifications (3% to 6% of samples) and CREBBP mutations (31% to 42% of samples) in the RR cohort, supported by acquisition of mutations in these genes in relapsed compared to diagnostic biopsies from the same patient. These increases may reflect the genetic characteristics of R-CHOP RR tumors expected to be enriched for during clinical trial enrollment. These findings hold significance for a number of emerging targeted therapies aligned to genetic targets and biomarkers in DLBCL, reinforcing the importance of time-of-treatment biomarker screening during DLBCL therapy selection. PMID:29245897

Routine hospital management of self-harm and risk of further self-harm: propensity score analysis using record-based cohort data.

PubMed

Steeg, S; Emsley, R; Carr, M; Cooper, J; Kapur, N

2018-01-01

The care received by people presenting to hospital following self-harm varies and it is unclear how different types of treatment affect risk of further self-harm. Observational cohort data from the Manchester Self-Harm Project, UK, included 16 456 individuals presenting to an Emergency Department with self-harm between 2003 and 2011. Individuals were followed up for 12 months. We also used data from a smaller cohort of individuals presenting to 31 hospitals in England during a 3-month period in 2010/2011, followed up for 6 months. Propensity score (PS) methods were used to address observed confounding. Missing data were imputed using multiple imputation. Following PS stratification, those who received a psychosocial assessment had a lower risk of repeat hospital attendance for self-harm than those who were not assessed [RR 0.87, 95% confidence interval (CI) 0.80-0.95]. The risk was reduced most among people less likely to be assessed. Following PS matching, we found no associations between risks of repeat self-harm and admission to a medical bed, referral to outpatient psychiatry or admission to a psychiatric bed. We did not find a relationship between psychosocial assessment and repeat self-harm in the 31 centre cohort. This study shows the potential value of using novel statistical techniques in large mental health datasets to estimate treatment effects. We found that specialist psychosocial assessment may reduce the risk of repeat self-harm. This type of routine care should be provided for all individuals who present to hospital after self-harm, regardless of perceived risk.

The association of BMI and outcomes in metastatic melanoma: A retrospective, multicohort analysis of patients treated with targeted therapy, immunotherapy, or chemotherapy

PubMed Central

McQuade, Jennifer L.; Daniel, Carrie R.; Hess, Kenneth R.; Mak, Carmen; Wang, Daniel Y.; Rai, Rajat R.; Park, John J.; Haydu, Lauren E.; Spencer, Christine; Wongchenko, Matthew; Lane, Stephen; Lee, Dung-Yang; Kaper, Mathilde; McKean, Meredith; Beckermann, Kathryn E; Rubinstein, Samuel M.; Rooney, Isabelle; Musib, Luna; Budha, Nageshwar; Hsu, Jessie; Nowicki, Theodore S.; Avila, Alexandre; Haas, Tomas; Puligandla, Maneka; Lee, Sandra; Fang, Shenying; Wargo, Jennifer A.; Gershenwald, Jeffrey E; Lee, Jeffrey E.; Hwu, Patrick; Chapman, Paul B.; Sosman, Jeffrey A.; Schadendorf, Dirk; Grob, Jean-Jacques; Flaherty, Keith T.; Walker, Dana; Yan, Yibing; McKenna, Edward; Legos, Jeffrey J.; Carlino, Matteo S.; Ribas, Antoni; Kirkwood, John M.; Long, Georgina V.; Johnson, Douglas B.; Menzies, Alexander M; Davies, Michael A.

2018-01-01

Background Obesity has been linked to increased mortality in several cancer types; however, the relationship between obesity and survival in metastatic melanoma is unknown. The aim of this study was to examine the association between BMI, progression-free survival (PFS), and overall survival (OS) in metastatic melanoma. Methods This study included 6 independent cohorts for a total of 1918 metastatic melanoma patients. These included two targeted therapy cohorts [randomized control trials (RCTs) of dabrafenib and trametinib (n=599) and vemurafenib and cobimetinib (n=240)], two immunotherapy cohorts [RCT of ipilimumab + dacarbazine (DTIC) (n=207) and a retrospective cohort treated with anti-PD-1/PDL-1 (n=331)], and two chemotherapy cohorts [RCT DTIC cohorts (n=320 and n=221)]. BMI was classified as normal (BMI 18 to <25; n=694 of 1918, 36.1%) overweight (BMI 25-29.9; n=711, 37.1%) or obese (BMI≥30; n=513, 26.7%). The primary outcomes were the association between BMI, PFS, and OS, stratified by treatment type and sex. These exploratory analyses were based on previously reported intention-to-treat data from the RCTs. The effect of BMI on PFS and OS was assessed by multivariable-adjusted Cox models in independent cohorts. In order to provide a more precise estimate of the association between BMI and outcomes, as well as the interaction between BMI, sex, and therapy type, adjusted hazard ratios were combined in mixed-effects meta-analyses and heterogeneity was explored with meta-regression analyses. Findings In the pooled analysis, obesity, as compared to normal BMI, was associated with improved survival in patients with metastatic melanoma [average adjusted hazard ratio (HR) and 95% CI: 0.77 (0.66-0.90) and 0.74 (0.58-0.95) for PFS and OS, respectively]. The survival benefit associated with obesity was restricted to patients treated with targeted therapy [0.72 (0.57-0.91) and 0.60 (0.45-0.79) for PFS and OS, respectively] and immunotherapy [0.75 (0.56-1.00) and 0.64 (0.47-0.86)]. No associations were observed with chemotherapy [0.87 (0.65-1.17) and 1.03 (0.80-1.34); treatment p for interaction = 0.61 and 0.01, for PFS and OS, respectively]. The prognostic effect of BMI with targeted and immune therapies differed by sex with pronounced inverse associations in males [PFS 0.67 (0.53-0.84) and OS 0.53 (0.40-0.70)], but not females [PFS 0.92 (0.70-1.23) and OS 0.85 (0.61-1.18), sex p for interaction= 0.08 and 0.03, for PFS and OS, respectively] Interpretation Obesity is associated with improved PFS and OS in metastatic melanoma, driven by strong associations observed in males treated with targeted or immune therapy. The magnitude of the benefit detected supports the need for investigation into the underlying mechanism of these unexpected observations Funding ASCO/CCF Young Investigator Award and ASCO/CCF Career Development Award to JLM PMID:29449192

Apolipoprotein E Genotype in Very Preterm Neonates with Intrauterine Growth Restriction: An Analysis of the German Neonatal Network Cohort.

PubMed

Norda, Stephen; Rausch, Tanja K; Orlikowsky, Thorsten; Hütten, Matthias; Schulz, Sören; Göpel, Wolfgang; Pecks, Ulrich

2017-01-01

Aim. Cord blood of intrauterine growth restricted (IUGR) neonates displays lipid changes towards atherosclerotic profiles. Apolipoprotein E (ApoE) and its isoforms (e2, e3, and e4) are involved in the regulation of lipid metabolism. Specifically, ApoE e4 has been associated with atherosclerotic diseases, while e2 has a favorable effect. We therefore hypothesized that ApoE e4 haplotype is frequently observed in IUGR neonates and contributes to impaired fetal growth and the association of IUGR with cardiovascular and metabolic diseases later in life. Methods. A cohort of 4885 preterm infants (≥22+0 and <32+0 weeks of gestation and birth weight below 1500 g) from the GNN study cohort was analyzed. Neonates were categorized into subgroups of <3rd, 3rd-10th, and >10th birth weight percentile. Analysis of the single nucleotides rs429358 and rs7412, identifying the ApoE genotype, was carried out using TaqMan® SNP genotyping assays. The proportional odds model was used to assess data. Results. No association was found between genotype and birth weight percentiles in each of the subgroups. Conclusion. ApoE genotype and low birth weight depict two distinct risk factors for cardiovascular disease without being directly associated.

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.

Association of coffee consumption with risk of colorectal cancer: a meta-analysis of prospective cohort studies.

PubMed

Gan, Yong; Wu, Jiang; Zhang, Shengchao; Li, Liqing; Cao, Shiyi; Mkandawire, Naomie; Ji, Kun; Herath, Chulani; Gao, Chao; Xu, Hong; Zhou, Yanfeng; Song, Xingyue; Chen, Shanquan; Chen, Yawen; Yang, Tingting; Li, Jing; Qiao, Yan; Hu, Sai; Yin, Xiaoxv; Lu, Zuxun

2017-03-21

A meta-analysis was performed to assess the association of coffee consumption with colorectal cancer and to investigate the shape of the association. Relevant prospective cohort studies were identified by a comprehensive search of the PubMed, Embase and Web of Science databases from their inception through August 2015. Either a random-effects model or fixed-effects model was used to compute the pooled risk estimates when appropriate. Linear and nonlinear dose-response meta-analyses were also performed. Nineteen prospective cohort studies involving 2,046,575 participants and 22,629 patients with colorectal cancer were included. The risk of colon cancer was decreased by 7% for every 4 cups per day of coffee (RR=0.93, 95%CI, 0.88-0.99; P=0.199). There was a threshold approximately five cups of coffee per day, and the inverse association for colorectal cancer appeared to be stronger at a higher range of intake. However, a nonlinear association of rectal cancer with coffee consumption was not observed (P for nonlinearity = 0.214). In conclusion, coffee consumption is significantly associated with a decreased risk of colorectal cancer at ≥ 5 cups per day of coffee consumption. The findings support the recommendations of including coffee as a healthy beverage for the prevention of colorectal cancer.

Association of coffee consumption with risk of colorectal cancer: a meta-analysis of prospective cohort studies

PubMed Central

Zhang, Shengchao; Li, Liqing; Cao, Shiyi; Mkandawire, Naomie; Ji, Kun; Herath, Chulani; Gao, Chao; Xu, Hong; Zhou, Yanfeng; Song, Xingyue; Chen, Shanquan; Chen, Yawen; Yang, Tingting; Li, Jing; Qiao, Yan; Hu, Sai; Yin, Xiaoxv; Lu, Zuxun

2017-01-01

A meta-analysis was performed to assess the association of coffee consumption with colorectal cancer and to investigate the shape of the association. Relevant prospective cohort studies were identified by a comprehensive search of the PubMed, Embase and Web of Science databases from their inception through August 2015. Either a random-effects model or fixed-effects model was used to compute the pooled risk estimates when appropriate. Linear and nonlinear dose-response meta-analyses were also performed. Nineteen prospective cohort studies involving 2,046,575 participants and 22,629 patients with colorectal cancer were included. The risk of colon cancer was decreased by 7% for every 4 cups per day of coffee (RR=0.93, 95%CI, 0.88-0.99; P=0.199). There was a threshold approximately five cups of coffee per day, and the inverse association for colorectal cancer appeared to be stronger at a higher range of intake. However, a nonlinear association of rectal cancer with coffee consumption was not observed (P for nonlinearity = 0.214). In conclusion, coffee consumption is significantly associated with a decreased risk of colorectal cancer at ≥ 5 cups per day of coffee consumption. The findings support the recommendations of including coffee as a healthy beverage for the prevention of colorectal cancer. PMID:27078843

Dietary fat intake and endometrial cancer risk

PubMed Central

Zhao, Jing; Lyu, Chen; Gao, Jian; Du, Li; Shan, Boer; Zhang, Hong; Wang, Hua-Ying; Gao, Ying

2016-01-01

Abstract Since body fatness is a convincing risk factor for endometrial cancer, dietary fat intake was speculated to be associated with endometrial cancer risk. However, epidemiological studies are inconclusive. We aimed to conduct a meta-analysis to assess the associations between dietary fat intake and endometrial cancer risk. We searched the PubMed, Embase, and Web of science databases updated to September 2015. In total, 7 cohort and 14 case–control studies were included. Pooled analysis of case–control studies suggested that endometrial cancer risk was significantly increased by 5% per 10% kilocalories from total fat intake (P=0.02) and by 17% per 10 g/1000 kcal of saturated fat intake (P < 0.001). Summary of 3 cohort studies showed significant inverse association between monounsaturated fatty acids and endometrial cancer risk (odds ratio = 0.84, 95% confidence interval = 0.73–0.98) with a total of 524583 participants and 3503 incident cases. No significant associations were found for polyunsaturated fatty acids and linoleic acid. In conclusion, positive associations with endometrial cancer risk were observed for total fat and saturated fat intake in the case–control studies. Results from the cohort studies suggested higher monounsaturated fatty acids intake was significantly associated with lower endometrial cancer risk. PMID:27399120

Breastfeeding, Bottle Feeding Practices and Malocclusion in the Primary Dentition: A Systematic Review of Cohort Studies

PubMed Central

Hermont, Ana Paula; Martins, Carolina C.; Zina, Lívia G.; Auad, Sheyla M.; Paiva, Saul M.; Pordeus, Isabela A.

2015-01-01

The World Health Organization recommends exclusive breast feeding for at least six months. However, there is no scientific evidence of the benefits of breast feeding for oral health in children under primary dentition. This study aimed to search for scientific evidence regarding the following question: is bottle feeding associated with malocclusion in the primary dentition compared to children that are breastfed? An electronic search was performed in seven databases. The systematic review included 10 cohort studies. It was not possible to conduct meta-analysis; therefore a qualitative analysis was assessed. The majority of studies evaluated feeding habits by means of questionnaires and conducted a single examination. Three studies observed that bottle feeding was significantly associated with overjet and posterior crossbite. Studies reported several cut-off times for breastfeeding (varying from 1 month up to 3 years of age) and several types of malocclusion. Controlling for non-nutritive sucking habits was reported for only half of the studies and this may have led to biased results. The scientific evidence could not confirm a specific type of malocclusion associated with the feeding habits or an adequate time of breastfeeding to benefit the children against malocclusion. Further cohort studies are needed to confirm this evidence. PMID:25785498

Differences in rates of switchbacks after switching from branded to authorized generic and branded to generic drug products: cohort study

PubMed Central

Sarpatwari, Ameet; Dejene, Sara; Khan, Nazleen F; Lii, Joyce; Rogers, James R; Dutcher, Sarah K; Raofi, Saeid; Bohn, Justin; Connolly, John; Fischer, Michael A; Kesselheim, Aaron S; Gagne, Joshua J

2018-01-01

Abstract Objectives To compare rates of switchbacks to branded drug products for patients switched from branded to authorized generic drug products, which have the same active ingredients, appearance, and excipients as the branded product, with patients switched from branded to generic drug products, which have the same active ingredients as the branded product but may differ in appearance and excipients. Design Observational cohort study. Setting Private (a large commercial health plan) and public (Medicaid) insurance programs in the US. Participants Beneficiaries of a large US commercial health insurer between 2004 and 2013 (primary cohort) and Medicaid beneficiaries between 2000 and 2010 (replication cohort). Main outcome measures Patients taking branded products for one of the study drugs (alendronate tablets, amlodipine tablets, amlodipine-benazepril capsules, calcitonin salmon nasal spray, escitalopram tablets, glipizide extended release tablets, quinapril tablets, and sertraline tablets) were identified when they switched to an authorized generic or a generic drug product after the date of market entry of generic drug products. These patients were followed for switchbacks to the branded drug product in the year after their switch to an authorized generic or a generic drug product. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals after adjusting for demographics, including age, sex, and calendar year. Inverse variance meta-analysis was used to pool adjusted hazard ratios across all drug products. Results A total of 94 909 patients switched from branded to authorized generic drug products and 116 017 patients switched from branded to generic drug products and contributed to the switchback analysis. Unadjusted incidence rates of switchback varied across drug products, ranging from a low of 3.8 per 100 person years (for alendronate tablets) to a high of 17.8 per 100 person years (for amlodipine-benazepril capsules), with an overall rate of 8.2 per 100 person years across all drug products. Adjusted switchback rates were consistently lower for patients who switched from branded to authorized generic drug products compared with branded to generic drug products in the primary cohort (pooled hazard ratio 0.72, 95% confidence interval 0.64 to 0.81). Similar results (0.75, 0.62 to 0.91) were observed in the replication cohort. Conclusion Switching from branded to authorized generic drug products was associated with lower switchback rates compared with switching from branded to generic drug products. PMID:29615391

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.

The relationship between transorbital ultrasound measurement of the optic nerve sheath diameter (ONSD) and invasively measured ICP in children : Part I: repeatability, observer variability and general analysis.

PubMed

Padayachy, Llewellyn C; Padayachy, Vaishali; Galal, Ushma; Gray, Rebecca; Fieggen, A Graham

2016-10-01

The aim of this study was to investigate the relationship between optic nerve sheath diameter (ONSD) measurement and invasively measured intracranial pressure (ICP) in children. ONSD measurement was performed prior to invasive measurement of ICP. The mean binocular ONSD measurement was compared to the ICP reading. Physiological variables including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse rate, temperature, respiratory rate and end tidal carbon dioxide (ETCO2) level were recorded at the time of ONSD measurement. Diagnostic accuracy analysis was performed at various ICP thresholds and  repeatability, intra- and inter-observer variability, correlation between measurements in different imaging planes as well the relationship over the entire patient cohort were examined in part I of this study. Data from 174 patients were analysed. Repeatability and intra-observer variability were excellent (α = 0.97-0.99). Testing for inter-observer variability revealed good correlation (r = 0.89, p < 0.001). Imaging in the sagittal plane demonstrated a slightly better correlation with ICP (r = 0.66, p < 0.001). The ONSD measurement with the best diagnostic accuracy for detecting an ICP ≥ 20 mmHg over the entire patient cohort was 5.5 mm, sensitivity 93.2 %, specificity 74 % and odds ratio (OR) of 39.3. Transorbital ultrasound measurement of the OSND is a reliable and reproducible technique, demonstrating a good relationship with ICP and high diagnostic accuracy for detecting raised ICP.

Internal limiting membrane peeling or not: a systematic review and meta-analysis of idiopathic macular pucker surgery.

PubMed

Fang, Xiao-Ling; Tong, Yao; Zhou, Ya-Li; Zhao, Pei-Quan; Wang, Zhao-Yang

2017-11-01

To determine whether internal limiting membrane (ILM) peeling improves anatomical and functional outcomes in idiopathic macular pucker (IMP)/epiretinal membrane (ERM) surgery in this systematic review and meta-analysis. We searched the PubMed, Medline, Web of Science, Cochrane, Ovid MEDLINE, ClinicalTrials.gov and CNKI databases for studies published before 15 September 2016. The eligibility criteria included studies comparing ILM peeling versus no-peeling for IMP surgery. Thirteen articles (10 retrospective cohort studies, 1 prospective cohort study and 2 randomised controlled trials (RCTs)) were included in the review. Primary outcomes: no differences were observed in the best-corrected visual acuity (BCVA) or central macular thickness (CMT) at 12 months; however, lower ERM recurrence (OR, 0.13; 95% CI 0.04 to 0.41; p=0.0004) and reoperation rates (OR, 0.10; 95% CI 0.02 to 0.49; p=0.004) that favoured ILM peeling were observed at the final follow-up. no difference was observed in BCVA at 3, 6 months, the final follow-up or in CMT at 3, 6 months, the final follow-up. Significantly increased CMT, which favoured ILM peeling, was observed at the final follow-up (p=0.002) in the RCTs. ILM peeling yielded greater anatomical success, but no improvement in functional outcomes as the treatment of choice for patients undergoing IMP surgery. 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/.

Mortality in the cotton industry workers: results of a cohort study.

PubMed

Szeszenia-Dabrowska, N; Wilczyńska, U; Strzelecka, A; Sobala, W

1999-01-01

The cohort consisted of persons found on the payroll of one of the Lódź cotton plants in 1964-1993 who were employed in the plant for at least 10 years. Death risk by causes was analysed using standardised mortality ratios (SMRs) calculated by the person-years method. The general population of Poland was used as the reference. In all, 7892 people were observed. As of December 31, 1995, the follow-up was completed for 7545 people (2852 men and 4693 women), i.e. the availability of the cohort was 95.6%. A total of 2069 deaths were recorded; the information on the cause of death was available for 97% of the subjects. In the male cohort, the level of the general mortality was the same as in the general population (SMR = 99). However, there was a significant increase in the number of deaths from diseases of the digestive system (SMR = 142) and larynx cancer (SMR = 188). The analysis of the results by production departments revealed in the weaving department significantly higher mortality from atherosclerosis (SMR = 141), peritoneal carcinoma (SMR = 1057) and melanoma (SMR = 677); and in the spinning department the increased risk of the hypertensive disease (SMR = 239), atherosclerosis (SMR = 175), and Hodgkin's disease (SMR = 768). Mortality in the female cohort was lower than that in the general population (SMR = 88). None of the disease groups or tumour sites caused statistically significant excess deaths either in the total cohort or in subcohorts selected according to departments. Special attention was paid to the chemical processing departments where chemicals used could contribute to the increased risk of death from cancer. Our analysis did not reveal any significant increase either in the total cohort of the workers employed in those departments or in the cohorts analyzed by duration of employment. Our results confirm the lower risk of lung cancer in the analysed group as compared with that in the general population. The numerous, but statistically insignificant increases in the incidence of malignant tumours at some specific sites detected in the subcohorts, distinguished according to the duration of employment or department, confirm the reported findings on the incidence of oral cavity, nose, throat, and larynx tumours among people exposed to harmful agents in the cotton industry.

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.

Influence of birth cohort on age of onset cluster analysis in bipolar I disorder.

PubMed

Bauer, M; Glenn, T; Alda, M; Andreassen, O A; Angelopoulos, E; Ardau, R; Baethge, C; Bauer, R; Bellivier, F; Belmaker, R H; Berk, M; Bjella, T D; Bossini, L; Bersudsky, Y; Cheung, E Y W; Conell, J; Del Zompo, M; Dodd, S; Etain, B; Fagiolini, A; Frye, M A; Fountoulakis, K N; Garneau-Fournier, J; Gonzalez-Pinto, A; Harima, H; Hassel, S; Henry, C; Iacovides, A; Isometsä, E T; Kapczinski, F; Kliwicki, S; König, B; Krogh, R; Kunz, M; Lafer, B; Larsen, E R; Lewitzka, U; Lopez-Jaramillo, C; MacQueen, G; Manchia, M; Marsh, W; Martinez-Cengotitabengoa, M; Melle, I; Monteith, S; Morken, G; Munoz, R; Nery, F G; O'Donovan, C; Osher, Y; Pfennig, A; Quiroz, D; Ramesar, R; Rasgon, N; Reif, A; Ritter, P; Rybakowski, J K; Sagduyu, K; Scippa, A M; Severus, E; Simhandl, C; Stein, D J; Strejilevich, S; Hatim Sulaiman, A; Suominen, K; Tagata, H; Tatebayashi, Y; Torrent, C; Vieta, E; Viswanath, B; Wanchoo, M J; Zetin, M; Whybrow, P C

2015-01-01

Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

PubMed

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

2017-01-01

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

Body mass index increases risk of colorectal adenomas in men with Lynch syndrome: the GEOLynch cohort study.

PubMed

Botma, Akke; Nagengast, Fokko M; Braem, Marieke G M; Hendriks, Jan C M; Kleibeuker, Jan H; Vasen, Hans F A; Kampman, Ellen

2010-10-01

High body mass index (BMI) is an established risk factor for sporadic colorectal cancer. Still, the influence of BMI on hereditary colorectal cancer (eg, Lynch syndrome [LS]), is unknown. The objective of this study was to assess whether BMI is associated with colorectal adenoma occurrence in persons with LS. A prospective cohort study of 486 patients with LS was conducted. Cox regression models with robust sandwich estimates controlling for age, sex, extent of colon surgery, smoking, and alcohol intake were used to evaluate associations between BMI, height, weight, weight change, and risk of colorectal adenomas. Analyses were performed separately for those without (incident cohort; n = 243) and those with (prevalent cohort; n = 243) a history of colorectal cancer neoplasms at baseline. A statistically significant association between current overweight (≥ 25 kg/m(2)) and developing colorectal adenomas was seen among men in the incident cohort (overweight v normal weight hazard ratio [HR], 8.72; 95% CI, 2.06 to 36.96). This association was not observed among women (overweight v normal weight HR, 0.75; 95% CI, 0.19 to 3.07), nor was it observed in the prevalent cohort. In the incident cohort, height was statistically significantly associated with a decreased risk of adenomatous polyps among men (per 5 cm HR, 0.43; 95% CI, 0.23 to 0.83), but the association between weight and adenomatous polyps among men was of marginal significance (per 5 kg HR, 1.17; 95% CI, 1.00 to 1.37). No statistically significant associations were observed among women in either the incident cohort or the prevalent cohort. Excess body weight increased the risk of incident colorectal adenomas in people with LS. This increased risk was seen only in men.

Apparent and internal validity of a Monte Carlo-Markov model for cardiovascular disease in a cohort follow-up study.

PubMed

Nijhuis, Rogier L; Stijnen, Theo; Peeters, Anna; Witteman, Jacqueline C M; Hofman, Albert; Hunink, M G Myriam

2006-01-01

To determine the apparent and internal validity of the Rotterdam Ischemic heart disease & Stroke Computer (RISC) model, a Monte Carlo-Markov model, designed to evaluate the impact of cardiovascular disease (CVD) risk factors and their modification on life expectancy (LE) and cardiovascular disease-free LE (DFLE) in a general population (hereinafter, these will be referred to together as (DF)LE). The model is based on data from the Rotterdam Study, a cohort follow-up study of 6871 subjects aged 55 years and older who visited the research center for risk factor assessment at baseline (1990-1993) and completed a follow-up visit 7 years later (original cohort). The transition probabilities and risk factor trends used in the RISC model were based on data from 3501 subjects (the study cohort). To validate the RISC model, the number of simulated CVD events during 7 years' follow-up were compared with the observed number of events in the study cohort and the original cohort, respectively, and simulated (DF)LEs were compared with the (DF)LEs calculated from multistate life tables. Both in the study cohort and in the original cohort, the simulated distribution of CVD events was consistent with the observed number of events (CVD deaths: 7.1% v. 6.6% and 7.4% v. 7.6%, respectively; non-CVD deaths: 11.2% v. 11.5% and 12.9% v. 13.0%, respectively). The distribution of (DF)LEs estimated with the RISC model consistently encompassed the (DF)LEs calculated with multistate life tables. The simulated events and (DF)LE estimates from the RISC model are consistent with observed data from a cohort follow-up study.

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.

Do changing levels of maternal exercise during pregnancy affect neonatal adiposity? Secondary analysis of the babies after SCOPE: evaluating the longitudinal impact using neurological and nutritional endpoints (BASELINE) birth cohort (Cork, Ireland)

PubMed Central

Norris, Tom; McCarthy, Fergus P; Khashan, Ali S; Murray, Deidre M; Kiely, Mairead; Hourihane, Jonathan O’B; Baker, Philip N; Kenny, Louise C

2017-01-01

Objective To investigate whether changing levels of exercise during pregnancy are related to altered neonatal adiposity. Design Secondary analysis of data from a prospective cohort study. Setting Cork, Ireland. Participants 1200 mother–infant pairs recruited as part of a prospective birth cohort, Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE). Main outcome measures Neonatal adiposity was assessed within several days of birth using air displacement plethysmography (PEAPOD). Per cent body fat (BF%) as a continuous outcome and a pair of dichotomous variables; high or low adiposity, representing BF% >90th or <10th centile, respectively. Multivariable linear and logistic regression models were used to investigate the relationship between exercise and the respective outcomes. Results Crude analysis revealed no association between a changing level of exercise (since becoming pregnant) at 15 weeks’ gestation and any of the outcomes (BF%, low adiposity and high adiposity). At 20 weeks’ gestation, analyses revealed that relative to women who do not change their exercise level up to 20 weeks, those women who decreased their exercise level were more likely to give birth to a neonate with adiposity above the 90th centile (OR 1.62, 95% CI 1.07 to 2.46). This association was maintained after adjustment for putative confounders (OR 1.62, 95% CI 1.06 to 2.47). Conclusions We observed a possible critical period for the association between changing exercise levels and neonatal adiposity, with no association observed with exercise recall for the first 15 weeks of gestation, but an association with a decreasing level of exercise between 15 and 20 weeks. These results should be interpreted in line with the limitations of the study and further studies utilising objectively measured estimates of exercise are required in order to replicate these findings. Trial registration number NCT01498965. PMID:29196482

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

PubMed Central

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

2011-01-01

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

Giant cell arteritis: diagnostic accuracy of MR imaging of superficial cranial arteries in initial diagnosis-results from a multicenter trial.

PubMed

Klink, Thorsten; Geiger, Julia; Both, Marcus; Ness, Thomas; Heinzelmann, Sonja; Reinhard, Matthias; Holl-Ulrich, Konstanze; Duwendag, Dirk; Vaith, Peter; Bley, Thorsten Alexander

2014-12-01

To assess the diagnostic accuracy of contrast material-enhanced magnetic resonance (MR) imaging of superficial cranial arteries in the initial diagnosis of giant cell arteritis ( GCA giant cell arteritis ). Following institutional review board approval and informed consent, 185 patients suspected of having GCA giant cell arteritis were included in a prospective three-university medical center trial. GCA giant cell arteritis was diagnosed or excluded clinically in all patients (reference standard [final clinical diagnosis]). In 53.0% of patients (98 of 185), temporal artery biopsy ( TAB temporal artery biopsy ) was performed (diagnostic standard [ TAB temporal artery biopsy ]). Two observers independently evaluated contrast-enhanced T1-weighted MR images of superficial cranial arteries by using a four-point scale. Diagnostic accuracy, involvement pattern, and systemic corticosteroid ( sCS systemic corticosteroid ) therapy effects were assessed in comparison with the reference standard (total study cohort) and separately in comparison with the diagnostic standard TAB temporal artery biopsy ( TAB temporal artery biopsy subcohort). Statistical analysis included diagnostic accuracy parameters, interobserver agreement, and receiver operating characteristic analysis. Sensitivity of MR imaging was 78.4% and specificity was 90.4% for the total study cohort, and sensitivity was 88.7% and specificity was 75.0% for the TAB temporal artery biopsy subcohort (first observer). Diagnostic accuracy was comparable for both observers, with good interobserver agreement ( TAB temporal artery biopsy subcohort, κ = 0.718; total study cohort, κ = 0.676). MR imaging scores were significantly higher in patients with GCA giant cell arteritis -positive results than in patients with GCA giant cell arteritis -negative results ( TAB temporal artery biopsy subcohort and total study cohort, P < .001). Diagnostic accuracy of MR imaging was high in patients without and with sCS systemic corticosteroid therapy for 5 days or fewer (area under the curve, ≥0.9) and was decreased in patients receiving sCS systemic corticosteroid therapy for 6-14 days. In 56.5% of patients with TAB temporal artery biopsy -positive results (35 of 62), MR imaging displayed symmetrical and simultaneous inflammation of arterial segments. MR imaging of superficial cranial arteries is accurate in the initial diagnosis of GCA giant cell arteritis . Sensitivity probably decreases after more than 5 days of sCS systemic corticosteroid therapy; thus, imaging should not be delayed. Clinical trial registration no. DRKS00000594 . © RSNA, 2014.

Antibiotic prescription strategies for acute sore throat: a prospective observational cohort study.

PubMed

Little, Paul; Stuart, Beth; Hobbs, F D Richard; Butler, Chris C; Hay, Alastair D; Delaney, Brendan; Campbell, John; Broomfield, Sue; Barratt, Paula; Hood, Kerenza; Everitt, Hazel; Mullee, Mark; Williamson, Ian; Mant, David; Moore, Michael

2014-03-01

Data from trials suggest that antibiotics reduce the risk of complications of sore throat by at least 50%, but few trials for complications have been done in modern settings, and datasets of delayed antibiotic prescription are underpowered. Observational evidence is important in view of poor compliance with antibiotic treatment outside trials, but no prospective observational cohort studies have been done to date. We generated a large prospective cohort from the DESCARTE study, and the PRISM component of DESCARTE, of 12,829 adults presenting with sore throat (≤ 2 weeks duration) in primary care. Our follow-up of the cohort was based on a detailed and structured review of routine medical records, and analysis of the comparison of three antibiotic prescription strategies (no antibiotic prescription, immediate antibiotic prescription, and delayed antibiotic prescription) to control for the propensity to prescribe antibiotics. Information about antibiotic prescription was recorded in 12,677 individuals (4805 prescribed no antibiotics, 6088 prescribed antibiotics immediately, and 1784 prescribed delayed antibiotics). We documented by review of patients' notes (n=11,950) the development of suppurative complications (eg, quinsy, impetigo and cellulitis, otitis media, and sinusitis) or reconsultation with new or non-resolving symptoms). We used multivariate analysis to control for variables significantly related to the propensity to prescribe antibiotics and for clustering by general practitioner. 164 (1.4%) of the 11,950 patients with information available developed complications; otitis media and sinusitis were the most common complications (101 patients [62%]). Compared with no antibiotic prescription, immediate antibiotic prescription was associated with fewer complications (adjusted risk ratio [RR] 0.62, 95% CI 0.43-0.91, estimated number needed to treat [NNT 193) as was delayed prescription of antibiotics (0.58, 0.34-0.98; NNT 174). 1787 of the 11,950 patients (15%) reconsulted with new or non-resolving symptoms; the risk of reconsultation was also reduced by immediate (0.83, 0.73-0.94; NNT 40) or delayed antibiotics (0.61, 0.50-0.74; NNT 18). Suppurative complications are not common in primary care and most are not serious. The risks of suppurative complications or reconsultation in adults are reduced by antibiotics, but not as much as the trial evidence suggests. In most cases, no antibiotic is needed, but a delayed prescription strategy is likely to provide similar benefits to an immediate antibiotic prescription. Copyright © 2014 Elsevier Ltd. All rights reserved.

Quality of Reporting and Study Design of CKD Cohort Studies Assessing Mortality in the Elderly Before and After STROBE: A Systematic Review

PubMed Central

Brück, Katharina; Methven, Shona; Evans, Rebecca; Stel, Vianda S.; Jager, Kitty J.; Hooft, Lotty; Ben-Shlomo, Yoav; Caskey, Fergus

2016-01-01

Background The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement was published in October 2007 to improve quality of reporting of observational studies. The aim of this review was to assess the impact of the STROBE statement on observational study reporting and study design quality in the nephrology literature. Study Design Systematic literature review. Setting & Population European and North American, Pre-dialysis Chronic Kidney Disease (CKD) cohort studies. Selection Criteria for Studies Studies assessing the association between CKD and mortality in the elderly (>65 years) published from 1st January 2002 to 31st December 2013 were included, following systematic searching of MEDLINE & EMBASE. Predictor Time period before and after the publication of the STROBE statement. Outcome Quality of study reporting using the STROBE statement and quality of study design using the Newcastle Ottawa Scale (NOS), Scottish Intercollegiate Guidelines Network (SIGN) and Critical Appraisal Skills Programme (CASP) tools. Results 37 papers (11 Pre & 26 Post STROBE) were identified from 3621 potential articles. Only four of the 22 STROBE items and their sub-criteria (objectives reporting, choice of quantitative groups and description of and carrying out sensitivity analysis) showed improvements, with the majority of items showing little change between the period before and after publication of the STROBE statement. Pre- and post-period analysis revealed a Manuscript STROBE score increase (median score 77.8% (Inter-quartile range [IQR], 64.7–82.0) vs 83% (IQR, 78.4–84.9, p = 0.05). There was no change in quality of study design with identical median scores in the two periods for NOS (Manuscript NOS score 88.9), SIGN (Manuscript SIGN score 83.3) and CASP (Manuscript CASP score 91.7) tools. Limitations Only 37 Studies from Europe and North America were included from one medical specialty. Assessment of study design largely reliant on good reporting. Conclusions This study highlights continuing deficiencies in the reporting of STROBE items and their sub-criteria in cohort studies in nephrology. There was weak evidence of improvement in the overall reporting quality, with no improvement in methodological quality of CKD cohort studies between the period before and after publication of the STROBE statement. PMID:27168187

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.

Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families

PubMed Central

Ansari, Morad; Balasubramanian, Meena; Blyth, Moira; Brady, Angela F.; Clayton, Stephen; Cole, Trevor; Deshpande, Charu; Fitzgerald, Tomas W.; Foulds, Nicola; Francis, Richard; Gabriel, George; Gerety, Sebastian S.; Goodship, Judith; Hobson, Emma; Jones, Wendy D.; Joss, Shelagh; King, Daniel; Klena, Nikolai; Kumar, Ajith; Lees, Melissa; Lelliott, Chris; Lord, Jenny; McMullan, Dominic; O'Regan, Mary; Osio, Deborah; Piombo, Virginia; Prigmore, Elena; Rajan, Diana; Rosser, Elisabeth; Sifrim, Alejandro; Smith, Audrey; Swaminathan, Ganesh J.; Turnpenny, Peter; Whitworth, James; Wright, Caroline F.; Firth, Helen V.; Barrett, Jeffrey C.; Lo, Cecilia W.; FitzPatrick, David R.; Hurles, Matthew E.

2018-01-01

Discovery of most autosomal recessive disease genes has involved analysis of large, often consanguineous, multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of novel dominant causes of rare, genetically heterogenous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios 1,2. Here we analysed 4,125 families with diverse, rare, genetically heterogeneous developmental disorders and identified four novel autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (identifying probands with rare biallelic putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population, and (ii) the phenotypic similarity of patients with the same recessive candidate gene. This new paradigm promises to catalyse discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations, and those caused predominantly by compound heterozygous genotypes. PMID:26437029

Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.

PubMed

Akawi, Nadia; McRae, Jeremy; Ansari, Morad; Balasubramanian, Meena; Blyth, Moira; Brady, Angela F; Clayton, Stephen; Cole, Trevor; Deshpande, Charu; Fitzgerald, Tomas W; Foulds, Nicola; Francis, Richard; Gabriel, George; Gerety, Sebastian S; Goodship, Judith; Hobson, Emma; Jones, Wendy D; Joss, Shelagh; King, Daniel; Klena, Nikolai; Kumar, Ajith; Lees, Melissa; Lelliott, Chris; Lord, Jenny; McMullan, Dominic; O'Regan, Mary; Osio, Deborah; Piombo, Virginia; Prigmore, Elena; Rajan, Diana; Rosser, Elisabeth; Sifrim, Alejandro; Smith, Audrey; Swaminathan, Ganesh J; Turnpenny, Peter; Whitworth, James; Wright, Caroline F; Firth, Helen V; Barrett, Jeffrey C; Lo, Cecilia W; FitzPatrick, David R; Hurles, Matthew E

2015-11-01

Discovery of most autosomal recessive disease-associated genes has involved analysis of large, often consanguineous multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of new dominant causes of rare, genetically heterogeneous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios. Here we analyzed 4,125 families with diverse, rare and genetically heterogeneous developmental disorders and identified four new autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (selecting probands with rare, biallelic and putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population and (ii) the phenotypic similarity of patients with recessive variants in the same candidate gene. This new paradigm promises to catalyze the discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations and those caused predominantly by compound heterozygous genotypes.

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.

The Association of Calcium Supplementation and Incident Cardiovascular Events in the Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Hsu, F.C.; de Boer, I.H.; Ix, J.H.; Siscovick, D.; Szklo, M.; Burke, G.L.; Frazier-Wood, A.C.; Herrington, D.M.

2016-01-01

Background and Aims Many US adults use calcium supplements to address inadequate dietary intake and improve bone health. However, recent reports have suggested that use of calcium supplements may elevate cardiovascular disease (CVD) risk. In this study, we examined associations between baseline calcium supplement use and incident myocardial infarction (MI) (n=208 events) and CVD events (n=641 events) over 10.3 years in men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n=6,236), with dietary calcium intake at baseline also examined as a supplementary objective. Methods and Results Using Cox proportional hazards models, no compelling associations between calcium intake from supplements or diet and incident CVD events were observed upon multivariate adjustment for potential confounders. An association with lower MI risk was observed comparing those with low levels of calcium supplement use (1-499 mg) to those using no calcium supplements (hazard ratio 0.69, 95% CI 0.48, 0.98, p=0.039). Relationships were homogeneous by gender, race/ethnicity, or chronic kidney disease. Results were also similar when the analysis was limited to postmenopausal women only. Conclusion Analysis of incident MI and CVD events in the MESA cohort does not support a substantial association of calcium supplement use with negative cardiovascular outcomes. PMID:27514606

Relationship between anticholinergic drug use and one-year outcome among elderly people hospitalised in medical wards via emergency department: the SAFES cohort study.

PubMed

Narbey, D; Jolly, D; Mahmoudi, R; Trenque, T; Blanchard, F; Novella, J-L; Dramé, M

2013-09-01

To investigate the relationship between anticholinergic drug use and one-year outcome of elderly patients hospitalised via the emergency department. Prospective, multicentre, cohort study of patients aged 75 years and older. Comprehensive geriatric evaluation was performed. We included in this analysis all patients for whom data on drug use was available. Anticholinergic drugs were coded using the online database "Thesorimed". One-year mortality and nursing home admission were analysed using a Cox model, with matching on the propensity to use anticholinergic drugs. In total, 1176 subjects were included in this analysis, average age 85±6 years, 65% women. Overall, 144 (12%) were taking at least one anticholinergic drug. Mortality and nursing home admission at one year were respectively 29% and 30% in the anticholinergic group, and 34% and 33% respectively in subjects not taking anticholinergic drugs. No significant relationship was observed between anticholinergic drug use and the main endpoints. Although we did not observed any statistically significant relationship between use of anticholinergic drugs and one-year outcome in elderly patients, the long-term use of anticholinergic drugs can have deleterious effects on memory and functional capacity, and therefore requires prescriptions to be reviewed regularly.

Association between ventilatory settings and development of acute respiratory distress syndrome in mechanically ventilated patients due to brain injury.

PubMed

Tejerina, Eva; Pelosi, Paolo; Muriel, Alfonso; Peñuelas, Oscar; Sutherasan, Yuda; Frutos-Vivar, Fernando; Nin, Nicolás; Davies, Andrew R; Rios, Fernando; Violi, Damian A; Raymondos, Konstantinos; Hurtado, Javier; González, Marco; Du, Bin; Amin, Pravin; Maggiore, Salvatore M; Thille, Arnaud W; Soares, Marco Antonio; Jibaja, Manuel; Villagomez, Asisclo J; Kuiper, Michael A; Koh, Younsuck; Moreno, Rui P; Zeggwagh, Amine Ali; Matamis, Dimitrios; Anzueto, Antonio; Ferguson, Niall D; Esteban, Andrés

2017-04-01

In neurologically critically ill patients with mechanical ventilation (MV), the development of acute respiratory distress syndrome (ARDS) is a major contributor to morbidity and mortality, but the role of ventilatory management has been scarcely evaluated. We evaluate the association of tidal volume, level of PEEP and driving pressure with the development of ARDS in a population of patients with brain injury. We performed a secondary analysis of a prospective, observational study on mechanical ventilation. We included 986 patients mechanically ventilated due to an acute brain injury (hemorrhagic stroke, ischemic stroke or brain trauma). Incidence of ARDS in this cohort was 3%. Multivariate analysis suggested that driving pressure could be associated with the development of ARDS (odds ratio for unit increment of driving pressure 1.12; confidence interval for 95%: 1.01 to 1.23) whereas we did not observe association for tidal volume (in ml per kg of predicted body weight) or level of PEEP. ARDS was associated with an increase in mortality, longer duration of mechanical ventilation, and longer ICU length of stay. In a cohort of brain-injured patients the development of ARDS was not common. Driving pressure was associated with the development of this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of glucocerebrosidase mutations on motor and nonmotor complications in Parkinson's disease.

PubMed

Oeda, Tomoko; Umemura, Atsushi; Mori, Yuko; Tomita, Satoshi; Kohsaka, Masayuki; Park, Kwiyoung; Inoue, Kimiko; Fujimura, Harutoshi; Hasegawa, Hiroshi; Sugiyama, Hiroshi; Sawada, Hideyuki

2015-12-01

Homozygous mutations of the glucocerebrosidase gene (GBA) cause Gaucher disease (GD), and heterozygous mutations of GBA are a major risk factor for Parkinson's disease (PD). This study examined the impact of GBA mutations on the longitudinal clinical course of PD patients by retrospective cohort design. GBA-coding regions were fully sequenced in 215 PD patients and GD-associated GBA mutations were identified in 19 (8.8%) PD patients. In a retrospective cohort study, time to develop dementia, psychosis, wearing-off, and dyskinesia were examined. Survival time analysis followed a maximum 12-year observation (median 6.0 years), revealing that PD patients with GD-associated mutations developed dementia and psychosis significantly earlier than those without mutations (p < 0.001 and p = 0.017, respectively). Adjusted hazard ratios of GBA mutations were 8.3 for dementia (p < 0.001) and 3.1 for psychosis (p = 0.002). No statistically significant differences were observed for wearing-off and dyskinesia between the groups. N-isopropyl-p[(123)I] iodoamphetamine single-photon emission tomography pixel-by-pixel analysis revealed that regional cerebral blood flow was reduced in the bilateral parietal cortex, including the precuneus of GD-associated mutant PD patients, compared with matched PD controls without mutations. Copyright © 2015 The Authors. Published by 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.

Management of Patients With Pancreatic Cysts: Analysis of Possible False-Negative Cases of Malignancy.

PubMed

Kowalski, Thomas; Siddiqui, Ali; Loren, David; Mertz, Howard R; Mallat, Damien; Haddad, Nadim; Malhotra, Nidhi; Sadowski, Brett; Lybik, Mark J; Patel, Sandeep N; Okoh, Emuejevoke; Rosenkranz, Laura; Karasik, Michael; Golioto, Michael; Linder, Jeffrey; Catalano, Marc F; Al-Haddad, Mohammad A

2016-09-01

To examine the utility of integrated molecular pathology (IMP) in managing surveillance of pancreatic cysts based on outcomes and analysis of false negatives (FNs) from a previously published cohort (n=492). In endoscopic ultrasound with fine-needle aspiration (EUS-FNA) of cyst fluid lacking malignant cytology, IMP demonstrated better risk stratification for malignancy at approximately 3 years' follow-up than International Consensus Guideline (Fukuoka) 2012 management recommendations in such cases. Patient outcomes and clinical features of Fukuoka and IMP FN cases were reviewed. Practical guidance for appropriate surveillance intervals and surgery decisions using IMP were derived from follow-up data, considering EUS-FNA sampling limitations and high-risk clinical circumstances observed. Surveillance intervals for patients based on IMP predictive value were compared with those of Fukuoka. Outcomes at follow-up for IMP low-risk diagnoses supported surveillance every 2 to 3 years, independent of cyst size, when EUS-FNA sampling limitations or high-risk clinical circumstances were absent. In 10 of 11 patients with FN IMP diagnoses (2% of cohort), EUS-FNA sampling limitations existed; Fukuoka identified high risk in 9 of 11 cases. In 4 of 6 FN cases by Fukuoka (1% of cohort), IMP identified high risk. Overall, 55% of cases had possible sampling limitations and 37% had high-risk clinical circumstances. Outcomes support more cautious management in such cases when using IMP. Adjunct use of IMP can provide evidence for relaxed surveillance of patients with benign cysts that meet Fukuoka criteria for closer observation or surgery. Although infrequent, FN results with IMP can be associated with EUS-FNA sampling limitations or high-risk clinical circumstances.

Dental Calculus Links Statistically to Angina Pectoris: 26-Year Observational Study.

PubMed

Söder, Birgitta; Meurman, Jukka H; Söder, Per-Östen

2016-01-01

Dental infections, such as periodontitis, associate with atherosclerosis and its complications. We studied a cohort followed-up since 1985 for incidence of angina pectoris with the hypothesis that calculus accumulation, proxy for poor oral hygiene, links to this symptom. In our Swedish prospective cohort study of 1676 randomly selected subjects followed-up for 26 years. In 1985 all subjects underwent clinical oral examination and answered a questionnaire assessing background variables such as socio-economic status and pack-years of smoking. By using data from the Center of Epidemiology, Swedish National Board of Health and Welfare, Sweden we analyzed the association of oral health parameters with the prevalence of in-hospital verified angina pectoris classified according to the WHO International Classification of Diseases, using descriptive statistics and logistic regression analysis. Of the 1676 subjects, 51 (28 women/23 men) had been diagnosed with angina pectoris at a mean age of 59.8 ± 2.9 years. No difference was observed in age and gender between patients with angina pectoris and subjects without. Neither was there any difference in education level and smoking habits (in pack years), Gingival index and Plaque index between the groups. Angina pectoris patients had significantly more often their first maxillary molar tooth extracted (d. 16) than the other subjects (p = 0.02). Patients also showed significantly higher dental calculus index values than the subjects without angina pectoris (p = 0.01). Multiple regression analysis showed odds ratio 2.21 (95% confidence interval 1.17-4.17) in the association between high calculus index and angina pectoris (p = 0.015). Our study hypothesis was confirmed by showing for the first time that high dental calculus score indeed associated with the incidence of angina pectoris in this cohort study.

Dental Calculus Links Statistically to Angina Pectoris: 26-Year Observational Study

PubMed Central

2016-01-01

Objectives Dental infections, such as periodontitis, associate with atherosclerosis and its complications. We studied a cohort followed-up since 1985 for incidence of angina pectoris with the hypothesis that calculus accumulation, proxy for poor oral hygiene, links to this symptom. Methods In our Swedish prospective cohort study of 1676 randomly selected subjects followed-up for 26 years. In 1985 all subjects underwent clinical oral examination and answered a questionnaire assessing background variables such as socio-economic status and pack-years of smoking. By using data from the Center of Epidemiology, Swedish National Board of Health and Welfare, Sweden we analyzed the association of oral health parameters with the prevalence of in-hospital verified angina pectoris classified according to the WHO International Classification of Diseases, using descriptive statistics and logistic regression analysis. Results Of the 1676 subjects, 51 (28 women/23 men) had been diagnosed with angina pectoris at a mean age of 59.8 ± 2.9 years. No difference was observed in age and gender between patients with angina pectoris and subjects without. Neither was there any difference in education level and smoking habits (in pack years), Gingival index and Plaque index between the groups. Angina pectoris patients had significantly more often their first maxillary molar tooth extracted (d. 16) than the other subjects (p = 0.02). Patients also showed significantly higher dental calculus index values than the subjects without angina pectoris (p = 0.01). Multiple regression analysis showed odds ratio 2.21 (95% confidence interval 1.17–4.17) in the association between high calculus index and angina pectoris (p = 0.015). Conclusion Our study hypothesis was confirmed by showing for the first time that high dental calculus score indeed associated with the incidence of angina pectoris in this cohort study. PMID:27336307

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.

Parental Separation and Cardiometabolic Risk Factors in Late Adolescence: A Cross-Cohort Comparison

PubMed Central

Soares, Ana Luiza Gonçalves; Gonçalves, Helen; Matijasevich, Alicia; Sequeira, Maija; Smith, George Davey; Menezes, Ana M. B.; Assunção, Maria Cecília; Wehrmeister, Fernando C.; Fraser, Abigail; Howe, Laura D.

2017-01-01

Abstract The aim of this study was to explore the association between parental separation during childhood (up to 18 years of age) and cardiometabolic risk factors (body mass index, fat mass index, blood pressure, physical activity, smoking, and alcohol consumption) in late adolescence using a cross-cohort comparison and to explore whether associations differ according to the age at which the parental separation occurred and the presence or absence of parental conflict prior to separation. Data from the Avon Longitudinal Study of Parents and Children (ALSPAC, United Kingdom) (1991–2011) and the 1993 Pelotas Birth Cohort (Brazil) (1993–2011) were used. The associations of parental separation with children's cardiometabolic risk factors were largely null. Higher odds of daily smoking were observed in both cohorts for those adolescents whose parents separated (for ALSPAC, odds ratio = 1.46; for Pelotas Birth Cohort, odds ratio = 1.98). Some additional associations were observed in the Pelotas Birth Cohort but were generally in the opposite direction to our a priori hypothesis: Parental separation was associated with lower blood pressure and fat mass index, and with more physical activity. No consistent differences were observed when analyses were stratified by child's age at parental separation or parental conflict. PMID:28444145

Phenotypes of COPD patients with a smoking history in Central and Eastern Europe: the POPE Study

PubMed Central

Koblizek, Vladimir; Milenkovic, Branislava; Barczyk, Adam; Tkacova, Ruzena; Somfay, Attila; Zykov, Kirill; Tudoric, Neven; Kostov, Kosta; Zbozinkova, Zuzana; Svancara, Jan; Sorli, Jurij; Krams, Alvils; Miravitlles, Marc

2017-01-01

Chronic obstructive pulmonary disease (COPD) represents a major health problem in Central and Eastern European (CEE) countries; however, there are no data regarding clinical phenotypes of these patients in this region. Participation in the Phenotypes of COPD in Central and Eastern Europe (POPE) study was offered to stable patients with COPD in a real-life setting. The primary aim of this study was to assess the prevalence of phenotypes according to predefined criteria. Secondary aims included analysis of differences in symptom load, comorbidities and pharmacological treatment. 3362 patients with COPD were recruited in 10 CEE countries. 63% of the population were nonexacerbators, 20.4% frequent exacerbators with chronic bronchitis, 9.5% frequent exacerbators without chronic bronchitis and 6.9% were classified as asthma–COPD overlap. Differences in the distribution of phenotypes between countries were observed, with the highest heterogeneity observed in the nonexacerbator cohort and the lowest heterogeneity observed in the asthma–COPD cohort. There were statistically significant differences in symptom load, lung function, comorbidities and treatment between these phenotypes. The majority of patients with stable COPD in CEE are nonexacerbators; however, there are distinct differences in surrogates of disease severity and therapy between predefined COPD phenotypes. PMID:28495687

Atypical lymphocytosis in leptospirosis: a cohort of hospitalized cases between 1996 and 2009 in State of Rio de Janeiro, Brazil.

PubMed

Damasco, Paulo Vieira; Avila, Carlos André Lins; Barbosa, Angélica Tápia; Ribeiro Carvalho, Marilza de Moura; Pereira, Geraldo Moura Batista; Lemos, Elba Regina Sampaio de; Bóia, Márcio Neves; Pereira, Martha Maria

2011-10-01

Leptospirosis is a zoonotic disease found in tropical and temperate countries, and its clinical diagnostic confusion with arboviruses (dengue fever, oropouche fever and yellow fever), Brazilian spotted fever, viral hepatitis and hantaviruses has been an ongoing public health concern. The aim of this observational study was to demonstrate an association between findings of atypical lymphocytosis and the progression of endemic leptospirosis. A retrospective analysis was performed on the demographic, epidemiological, clinical and laboratory aspects of 27 human leptospirosis cases that occurred over a period of 13 years (1996-2009) with no reported epidemic outbreaks in Rio de Janeiro, Brazil. The overall mortality rate was 11.1% in our cohort of hospitalized cases. However, there was no mortality among patients with atypical lymphocytosis (OR = 11.1; 95% CI = 1.12-110.9; p = 0.04). Two patients who were in the septicemic phase showed signs of expansion of γδ T cell responses in peripheral blood. Atypical lymphocytosis may be observed in patients with leptospirosis. Our observations suggest that these atypical leukocyte subsets are associated with partial protection during the disease course of leptospirosis.

Evaluation of the Pooled Cohort Equations for Prediction of Cardiovascular Risk in a Contemporary Prospective Cohort.

PubMed

Emdin, Connor A; Khera, Amit V; Natarajan, Pradeep; Klarin, Derek; Baber, Usman; Mehran, Roxana; Rader, Daniel J; Fuster, Valentin; Kathiresan, Sekar

2017-03-15

Most guidelines suggest a baseline risk assessment to guide atherosclerotic cardiovascular disease (ASCVD) prevention strategies. The American Heart Association/American College of Cardiology Pooled Cohort Equations (PCEs) is one tool to assess baseline risk; however, the accuracy of this tool has been called into question. We aimed to examine the calibration and discrimination of the PCEs in the BioImage study, a contemporary multiethnic cohort of asymptomatic adults enrolled from 2008 to 2009 in the Humana Health System in Chicago, Illinois, and Fort Lauderdale, Florida. Our primary end point was hard ASCVD, defined as cardiovascular death, myocardial infarction, and stroke. A total of 3,635 adults who were not on lipid-lowering therapy at baseline were followed for a maximum of 4.6 years. The mean age was 68.6 years; 2000 (55%) participants were women and 935 patients reported being of non-white race (26%). Although 74 ASCVD events were observed over a median follow-up of 2.7 years, 198 events were predicted by the PCEs. The observed event rate was 7.9 per 1,000 participant-years (95% confidence interval [CI] 6.1 to 9.8), whereas the predicted rate by the PCEs was 21 per 1,000 participant-years (95% CI 20.7 to 21.8). This represents an overestimation of 167% (Hosmer-Lemeshow chi-square = 173; p <0.001). With regard to discrimination, the C-statistic of the PCEs was 0.65 (CI 0.58 to 0.71). In an analysis restricted to 3,080 participants without diabetes mellitus and with low-density lipoprotein cholesterol between 70 and 189 mg/dl, the PCEs similarly overestimated risk by 181% (152 predicted events vs 54 observed events; p <0.001). The PCEs substantially overestimate ASCVD risk in this middle-aged adult insured population. Refinement of existing risk prediction functions may be warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular Characterization of “Candidatus Parilichlamydia carangidicola,” a Novel Chlamydia-Like Epitheliocystis Agent in Yellowtail Kingfish, Seriola lalandi (Valenciennes), and the Proposal of a New Family, “Candidatus Parilichlamydiaceae” fam. nov. (Order Chlamydiales)

PubMed Central

Polkinghorne, A.; Miller, T. L.; Groff, J. M.; LaPatra, S. E.; Nowak, B. F.

2013-01-01

Three cohorts of farmed yellowtail kingfish (Seriola lalandi) from South Australia were examined for Chlamydia-like organisms associated with epitheliocystis. To characterize the bacteria, 38 gill samples were processed for histopathology, electron microscopy, and 16S rRNA amplification, sequencing, and phylogenetic analysis. Microscopically, the presence of membrane-enclosed cysts was observed within the gill lamellae. Also observed was hyperplasia of the epithelial cells with cytoplasmic vacuolization and fusion of the gill lamellae. Transmission electron microscopy revealed morphological features of the reticulate and intermediate bodies typical of members of the order Chlamydiales. A novel 1,393-bp 16S chlamydial rRNA sequence was amplified from gill DNA extracted from fish in all cohorts over a 3-year period that corresponded to the 16S rRNA sequence amplified directly from laser-dissected cysts. This sequence was only 87% similar to the reported “Candidatus Piscichlamydia salmonis” (AY462244) from Atlantic salmon and Arctic charr. Phylogenetic analysis of this sequence against 35 Chlamydia and Chlamydia-like bacteria revealed that this novel bacterium belongs to an undescribed family lineage in the order Chlamydiales. Based on these observations, we propose this bacterium of yellowtail kingfish be known as “Candidatus Parilichlamydia carangidicola” and that the new family be known as “Candidatus Parilichlamydiaceae.” PMID:23275507

Meta-analysis of human genome-microbiome association studies: the MiBioGen consortium initiative.

PubMed

Wang, Jun; Kurilshikov, Alexander; Radjabzadeh, Djawad; Turpin, Williams; Croitoru, Kenneth; Bonder, Marc Jan; Jackson, Matthew A; Medina-Gomez, Carolina; Frost, Fabian; Homuth, Georg; Rühlemann, Malte; Hughes, David; Kim, Han-Na; Spector, Tim D; Bell, Jordana T; Steves, Claire J; Timpson, Nicolas; Franke, Andre; Wijmenga, Cisca; Meyer, Katie; Kacprowski, Tim; Franke, Lude; Paterson, Andrew D; Raes, Jeroen; Kraaij, Robert; Zhernakova, Alexandra

2018-06-08

In recent years, human microbiota, especially gut microbiota, have emerged as an important yet complex trait influencing human metabolism, immunology, and diseases. Many studies are investigating the forces underlying the observed variation, including the human genetic variants that shape human microbiota. Several preliminary genome-wide association studies (GWAS) have been completed, but more are necessary to achieve a fuller picture. Here, we announce the MiBioGen consortium initiative, which has assembled 18 population-level cohorts and some 19,000 participants. Its aim is to generate new knowledge for the rapidly developing field of microbiota research. Each cohort has surveyed the gut microbiome via 16S rRNA sequencing and genotyped their participants with full-genome SNP arrays. We have standardized the analytical pipelines for both the microbiota phenotypes and genotypes, and all the data have been processed using identical approaches. Our analysis of microbiome composition shows that we can reduce the potential artifacts introduced by technical differences in generating microbiota data. We are now in the process of benchmarking the association tests and performing meta-analyses of genome-wide associations. All pipeline and summary statistics results will be shared using public data repositories. We present the largest consortium to date devoted to microbiota-GWAS. We have adapted our analytical pipelines to suit multi-cohort analyses and expect to gain insight into host-microbiota cross-talk at the genome-wide level. And, as an open consortium, we invite more cohorts to join us (by contacting one of the corresponding authors) and to follow the analytical pipeline we have developed.

A comparison of risperidone and haloperidol for the risk of ischemic stroke in the elderly: a propensity score-matched cohort analysis.

PubMed

Shin, Ju-Young; Choi, Nam-Kyong; Lee, Joongyub; Park, Mi-Ju; Lee, Shin Haeng; Park, Byung-Joo

2015-08-01

With an increase in antipsychotic use in the elderly, the safety profile of antipsychotics has been emphasized. Strong concerns have been raised about whether the risk of ischemic stroke differs between risperidone and haloperidol. This study compared the risk of ischemic stroke between elderly patients taking risperidone and haloperidol. We conducted a retrospective cohort study using the Korea Health Insurance Review and Assessment Service database, applying a propensity-matched analysis. The cohort consisted of elderly patients who were newly prescribed haloperidol or risperidone between January 1, 2006 and December 31, 2009. Patients with prior cerebrovascular diseases (ICD-10, I60-I69), transient ischemic attack (ICD-10, G45), or cerebral tumors (ICD-10, C31) during 365 days prior to the initiation date were excluded. The study subjects were selected by propensity score matching. The outcome was defined as the first hospitalization for ischemic stroke (ICD-10, I63). Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) for ischemic stroke with haloperidol compared with risperidone use. A total of 14,103 patients were included in the propensity-matched cohort for each drug. Overall, the incidence rate was higher for haloperidol users compared to the risperidone users (6.43 per 1000 person-years vs. 2.88 per 1000 person-years). A substantially increased risk was observed in haloperidol users (adjusted HR = 2.02, 95% CI, 1.12-3.62). The evidence showed that haloperidol should be prescribed in the elderly with caution. © The Author(s) 2015.

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.

Kinship and mate choice in a historic eastern Blue Ridge community, Madison County, Virginia.

PubMed

Frankenberg, S R

1990-12-01

Potential mates analysis is difficult to apply to small historic populations that lack clear boundaries or regular vital event registration. Here I analyze the actual mate pool as an alternative way to identify causes of nonrandom mating when unmarried members are unknown. Factors influencing mate choice within a historic eastern Blue Ridge community in Madison County, Virginia, are examined for four marriage cohorts: 1850-1879, 1880-1899, 1900-1919, and 1920-1939. These factors include nuclear kin avoidance, preferred age differences between mates, and preferences for more distant kin. A simulation is used to recombine members of the cohort-specific pools of married individuals to generate the probabilities of various types of kin marriages. The pedigree and vital statistics data are derived from first-time marriage licenses filled by community members in Madison County from 1794 to 1939. The numbers of marriages examined for each cohort are 88, 120, 132, and 132, respectively; the mate pools constructed from the samples are viewed from the female perspective. The results generated by simulation on the actual mate pools consist of mean kinship coefficients, numbers of marriages between "allowed" kin types, and probabilities of these values when marriage is random with respect to kinship. The results indicate significantly high levels of inbreeding in all four marriage cohorts, primarily because of high levels of first-cousin marriages in the first three cohorts and of first-cousin once-removed marriages in the 1920 cohort. The observed mating patterns are discussed in terms of the social history of the Blue Ridge community and restrictions of the data.

Pregnancy outcome after first trimester use of angiotensin AT1 receptor blockers: an observational cohort study.

PubMed

Hoeltzenbein, Maria; Tissen-Diabaté, Tatjana; Fietz, Anne-Katrin; Zinke, Sandra; Kayser, Angela; Meister, Reinhard; Weber-Schoendorfer, Corinna; Schaefer, Christof

2018-03-24

Ongoing discussion about the safety of renin-angiotensin inhibitors in the first trimester and limited data on pregnancy outcomes after exposure to angiotensin AT1 receptor blockers (ARBs). Observational cohort study compares outcomes of 215 prospectively ascertained pregnancies with first trimester exposure to ARBs with 642 non-hypertensive pregnancies. The rate of major birth defects in the ARB cohort (9/168, 5.4%) was higher than in the comparison group (17/570, 3%), but not significantly increased (OR adj 1.9, 95% CI 0.7-4.9). There was no distinct pattern of anomalies among infants with birth defects. The risk of spontaneous abortions was not increased (HR adj 0.9, 95% CI 0.5-1.6), although the cumulative incidence was in the upper normal range (0.22, 95% CI 0.15-0.32). Higher rates of prematurity (OR adj 3.0; 95% CI 1.7-5.1) and a reduced birth weight after adjustment for sex and gestational age were observed. There was no evidence for an increased risk for major birth defects, spontaneous abortions, or preterm birth in a sensitivity analysis comparing ARB exposed hypertensive women to hypertensive women without ARB exposure during the first trimester. Our study supports the hypothesis that ARBs are not major teratogens. Patients inadvertently exposed to ARBs during the early pregnancy may be reassured. Nevertheless, women planning pregnancy should avoid ARBs. In selected cases, ARBs might be continued under careful monitoring of menstrual cycle and discontinued as soon as pregnancy is recognized.

Smoking and the risk of diabetic nephropathy in patients with type 1 and type 2 diabetes: a meta-analysis of observational studies.

PubMed

Jiang, Ning; Huang, Feng; Zhang, Xiurong

2017-11-03

Conflicting evidence exists for observational studies on whether tobacco smoking is a risk factor for diabetic nephropathy (DN) in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). In this meta-analysis, we aimed to assess the effects of tobacco smoking on the development of DN. We searched MEDLINE and EMBASE databases from their inception to March 31 st , 2017 for cross-sectional, case-control, and prospective cohort studies. We screened reference lists of retrieved articles. Summary relative risks (SRRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. A total of nineteen observational studies (1 case-control, 8 cross-sectional and 10 prospective cohort studies) were identified, involving more than 78,000 participants and a total of 17,832 DN cases. Compared with never-smokers, there was an augmented SRR (95% CI) of DN in ever-smokers in patients with T1DM (1.31 [1.06-1.62]; P = 0.006) and T2DM (1.44 [1.24-1.67]; P < 0.001), respectively. In patients with T1DM, the SRR (95% CI) was 1.25 (0.86-1.83) for microalbuminuria only, 1.27 (1.10-1.48) for macroalbuminuria only, and 1.06 (0.97-1.15) for end-stage renal disease (ESRD). In patients with T2DM, the SRR (95% CI) associated with ever smoking was 1.46 (0.94-2.26) for microalbuminuria only, 1.72 (1.04-2.84) for macroalbuminuria only, and 1.10 (0.36-3.33) for ESRD. Our meta-analysis suggests evidence for cigarette smoking as an independent risk factor for the development of DN in patients with both T1DM and T2DM.

Red and Processed Meat Consumption Increases Risk for Non-Hodgkin Lymphoma

PubMed Central

Yang, Li; Dong, Jianming; Jiang, Shenghua; Shi, Wenyu; Xu, Xiaohong; Huang, Hongming; You, Xuefen; Liu, Hong

2015-01-01

Abstract The association between consumption of red and processed meat and non-Hodgkin lymphoma (NHL) remains unclear. We performed a meta-analysis of the published observational studies to explore this relationship. We searched databases in MEDLINE and EMBASE to identify observational studies which evaluated the association between consumption of red and processed meat and risk of NHL. Quality of included studies was evaluated using Newcastle-Ottawa Quality Assessment Scale (NOS). Random-effects models were used to calculate summary relative risk (SRR) and the corresponding 95% confidence interval (CI). We identified a total of 16 case–control and 4 prospective cohort studies, including 15,189 subjects with NHL. The SRR of NHL comparing the highest and lowest categories were 1.32 (95% CI: 1.12–1.55) for red meat and 1.17 (95% CI: 1.07–1.29) for processed meat intake. Stratified analysis indicated that a statistically significant risk association between consumption of red and processed meat and NHL risk was observed in case–control studies, but not in cohort studies. The SRR was 1.11 (95% CI: 1.04–1.18) for per 100 g/day increment in red meat intake and 1.28 (95% CI: 1.08–1.53) for per 50 g/day increment in processed meat intake. There was evidence of a nonlinear association for intake of processed meat, but not for intake of red meat. Findings from our meta-analysis indicate that consumption of red and processed meat may be related to NHL risk. More prospective epidemiological studies that control for important confounders and focus on the NHL risk related with different levels of meat consumption are required to clarify this association. PMID:26559248

Dairy Products Intake and Endometrial Cancer Risk: A Meta-Analysis of Observational Studies

PubMed Central

2017-01-01

Observational studies have suggested inconsistent findings on the relationship between dairy products intake and endometrial cancer risk. This study aimed to conduct a meta-analysis to evaluate this correlation; moreover, databases including PubMed, ISI Web of Science, and Embase were screened for relevant studies up to 26 February 2017. The inverse variance weighting method and random effects models were used to calculate the overall OR (odds ratio) values and 95% confidence interval (CI). A total of 2 cohort study and 16 case-control studies were included in the current analysis. No significant association was observed between endometrial cancer risk and the intake of total dairy products, milk, or cheese for the highest versus the lowest exposure category (total dairy products (14 studies): OR 1.04, 95% CI: 0.97–1.11, I2 = 73%, p = 0.000; milk (6 studies): 0.99, 95% CI: 0.89–1.10, I2 = 0.0%, p = 0.43; cheese (5 studies): 0.89, 95% CI: 0.76–1.05, I2 = 39%, p = 0.16). The only cohort study with a total of 456,513 participants reported a positive association of butter intake with endometrial cancer risk (OR = 1.14; 95% CI = 1.03–1.26, I2 = 2.6%, p = 0.31). There was a significant negative association of dairy products intake and endometrial cancer risk among women with a higher body mass index (BMI) (5 studies, OR 0.66, 95% CI = 0.46–0.96, I2 = 75.8%, p = 0.002). Stratifying the analyses by risk factors including BMI should be taken into account when exploring the association of dairy products intake with endometrial cancer risk. Further well-designed studies are needed. PMID:29283380

Chocolate consumption and cardiometabolic disorders: systematic review and meta-analysis

PubMed Central

Buitrago-Lopez, Adriana; Sanderson, Jean; Johnson, Laura; Warnakula, Samantha; Wood, Angela; Di Angelantonio, Emanuele

2011-01-01

Objective To evaluate the association of chocolate consumption with the risk of developing cardiometabolic disorders. Design Systematic review and meta-analysis of randomised controlled trials and observational studies. Data sources Medline, Embase, Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, reference lists of relevant studies to October 2010, and email contact with authors. Study selection Randomised trials and cohort, case-control, and cross sectional studies carried out in human adults, in which the association between chocolate consumption and the risk of outcomes related to cardiometabolic disorders were reported. Data extraction Data were extracted by two independent investigators, and a consensus was reached with the involvement of a third. The primary outcome was cardiometabolic disorders, including cardiovascular disease (coronary heart disease and stroke), diabetes, and metabolic syndrome. A meta-analysis assessed the risk of developing cardiometabolic disorders by comparing the highest and lowest level of chocolate consumption. Results From 4576 references seven studies met the inclusion criteria (including 114 009 participants). None of the studies was a randomised trial, six were cohort studies, and one a cross sectional study. Large variation was observed between these seven studies for measurement of chocolate consumption, methods, and outcomes evaluated. Five of the seven studies reported a beneficial association between higher levels of chocolate consumption and the risk of cardiometabolic disorders. The highest levels of chocolate consumption were associated with a 37% reduction in cardiovascular disease (relative risk 0.63 (95% confidence interval 0.44 to 0.90)) and a 29% reduction in stroke compared with the lowest levels. Conclusions Based on observational evidence, levels of chocolate consumption seem to be associated with a substantial reduction in the risk of cardiometabolic disorders. Further experimental studies are required to confirm a potentially beneficial effect of chocolate consumption. PMID:21875885

Deregulation of sale of over-the-counter drugs outside of pharmacies in the Republic of Korea: interrupted-time-series analysis of outpatient visits before and after the policy.

PubMed

Chun, Sung-Youn; Park, Hye-Ki; Han, Kyu-Tae; Kim, Woorim; Lee, Hyo-Jung; Park, Eun-Cheol

2017-07-12

We evaluated the effectiveness of a policy allowing for the sale of over-the-counter drugs outside of pharmacies by examining its effect on number of monthly outpatient visits for acute upper respiratory infections, dyspepsia, and migraine. We used medical claims data extracted from the Korean National Health Insurance Cohort Database from 2009 to 2013. The Korean National Health Insurance Cohort Database comprises a nationally representative sample of claims - about 2% of the entire population - obtained from the medical record data held by the Korean National Health Insurance Corporation (which has data on the entire nation). The analysis included26,284,706 person-months of 1,042,728 individuals. An interrupted-time series analysis was performed. Outcome measures were monthly outpatient visits for acute upper respiratory infections, dyspepsia, and migraine. To investigate the effect of the policy, we compared the number of monthly visits before and after the policy's implementation in 2012. For acute upper respiratory infections, monthly outpatient visits showed a decreasing trend before the policy (ß = -0.0003);after it, a prompt change and increasing trend in monthly outpatient visits were observed, but these were non-significant. For dyspepsia, the trend was increasing before implementation (ß = -0.0101), but this reversed after implementation(ß = -0.007). For migraine, an increasing trend was observed before the policy (ß = 0.0057). After it, we observed a significant prompt change (ß = -0.0314) but no significant trend. Deregulation of selling over-the-counter medication outside of pharmacies reduced monthly outpatient visits for dyspepsia and migraine symptoms, but not acute upper respiratory infections.

Can commonly prescribed drugs be repurposed for the prevention or treatment of Alzheimer's and other neurodegenerative diseases? Protocol for an observational cohort study in the UK Clinical Practice Research Datalink.

PubMed

Walker, Venexia M; Davies, Neil M; Jones, Tim; Kehoe, Patrick G; Martin, Richard M

2016-12-13

Current treatments for Alzheimer's and other neurodegenerative diseases have only limited effectiveness meaning that there is an urgent need for new medications that could influence disease incidence and progression. We will investigate the potential of a selection of commonly prescribed drugs, as a more efficient and cost-effective method of identifying new drugs for the prevention or treatment of Alzheimer's disease, non-Alzheimer's disease dementias, Parkinson's disease and amyotrophic lateral sclerosis. Our research will focus on drugs used for the treatment of hypertension, hypercholesterolaemia and type 2 diabetes, all of which have previously been identified as potentially cerebroprotective and have variable levels of preclinical evidence that suggest they may have beneficial effects for various aspects of dementia pathology. We will conduct a hypothesis testing observational cohort study using data from the Clinical Practice Research Datalink (CPRD). Our analysis will consider four statistical methods, which have different approaches for modelling confounding. These are multivariable adjusted Cox regression; propensity matched regression; instrumental variable analysis and marginal structural models. We will also use an intention-to-treat analysis, whereby we will define all exposures based on the first prescription observed in the database so that the target parameter is comparable to that estimated by a randomised controlled trial. This protocol has been approved by the CPRD's Independent Scientific Advisory Committee (ISAC). We will publish the results of the study as open-access peer-reviewed publications and disseminate findings through national and international conferences as are appropriate. 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/.

Chocolate consumption and cardiometabolic disorders: systematic review and meta-analysis.

PubMed

Buitrago-Lopez, Adriana; Sanderson, Jean; Johnson, Laura; Warnakula, Samantha; Wood, Angela; Di Angelantonio, Emanuele; Franco, Oscar H

2011-08-26

To evaluate the association of chocolate consumption with the risk of developing cardiometabolic disorders. Systematic review and meta-analysis of randomised controlled trials and observational studies. Medline, Embase, Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, reference lists of relevant studies to October 2010, and email contact with authors. Randomised trials and cohort, case-control, and cross sectional studies carried out in human adults, in which the association between chocolate consumption and the risk of outcomes related to cardiometabolic disorders were reported. Data were extracted by two independent investigators, and a consensus was reached with the involvement of a third. The primary outcome was cardiometabolic disorders, including cardiovascular disease (coronary heart disease and stroke), diabetes, and metabolic syndrome. A meta-analysis assessed the risk of developing cardiometabolic disorders by comparing the highest and lowest level of chocolate consumption. From 4576 references seven studies met the inclusion criteria (including 114,009 participants). None of the studies was a randomised trial, six were cohort studies, and one a cross sectional study. Large variation was observed between these seven studies for measurement of chocolate consumption, methods, and outcomes evaluated. Five of the seven studies reported a beneficial association between higher levels of chocolate consumption and the risk of cardiometabolic disorders. The highest levels of chocolate consumption were associated with a 37% reduction in cardiovascular disease (relative risk 0.63 (95% confidence interval 0.44 to 0.90)) and a 29% reduction in stroke compared with the lowest levels. Based on observational evidence, levels of chocolate consumption seem to be associated with a substantial reduction in the risk of cardiometabolic disorders. Further experimental studies are required to confirm a potentially beneficial effect of chocolate consumption.

Real-life effectiveness and safety of salbutamol Steri-Neb™ vs. Ventolin Nebules® for exacerbations in patients with COPD: Historical cohort study

PubMed Central

Gefen, Eran; Gopalan, Gokul; McDonald, Rosie; Thomas, Vicky; Ming, Simon Wan Yau; Davis, Emily

2018-01-01

Introduction Ventolin Nebules® (reference product; GlaxoSmithKline) was the first licensed nebulizer solution containing the rapid-onset, short-acting β2-agonist salbutamol. Salbutamol Steri-Neb™ (comparator; Teva Pharmaceuticals, Inc.) has the same chemical composition as the reference product. This study evaluated whether the effectiveness of the comparator is non-inferior to the reference product alongside concomitant medications during real-life clinical management of COPD exacerbations. Safety in terms of adverse events (AEs) was also examined. Methods This matched (1:1) historical cohort study evaluated data from 2 UK primary care databases on patients prescribed the salbutamol comparator or reference. The study included a 1-year baseline period, starting 1 year before the index prescription date, and 1-year outcome period. Cohorts were matched for baseline COPD respiratory medications. The primary outcome was analysis of non-inferiority for the comparator versus reference product for the rate of moderate and severe COPD exacerbations. Non-inferiority was satisfied if the 95% confidence interval (CI) upper limit for mean differences in proportions between treatments was <15%. Secondary outcomes were examined through rate ratios (RR) of severe exacerbations and AEs. Results After matching, 1191 patients were included in each cohort. Adjusted upper 95% CI for the difference in proportion of patients experiencing moderate or severe exacerbations between comparator and reference groups was 0.032 (3.2%), demonstrating non-inferiority. No significant differences were observed in rates of moderate and severe exacerbations (RR: 1.00; 95% CI: 0.91, 1.10), severe exacerbations (RR: 0.76; 95% CI: 0.49, 1.17), or AEs (RR: 0.98; 95% CI: 0.78, 1.22) after adjusting for baseline confounders. No significant differences across cohorts were observed for rates of any AE or death. Conclusion This matched cohort study of real-life management of COPD patients supports the salbutamol comparator as non-inferior to the reference product, providing an effective treatment alternative for COPD exacerbations. Comparator and reference safety profiles were similar. PMID:29364929

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.

Clinical and Demographic Profile of Patients Receiving Fingolimod in Clinical Practice in Germany and the Benefit-Risk Profile of Fingolimod After 1 Year of Treatment: Initial Results From the Observational, Noninterventional Study PANGAEA.

PubMed

Ziemssen, Tjalf; Lang, Michael; Tackenberg, Björn; Schmidt, Stephan; Albrecht, Holger; Klotz, Luisa; Haas, Judith; Lassek, Christoph; Medin, Jennie; Cornelissen, Christian

2018-01-01

The population with multiple sclerosis receiving treatment in clinical practice differs from that in randomized controlled trials (RCTs). An assessment of the real-world benefit-risk profile of therapies is needed. This analysis used data from the large, noninterventional, observational German study Post-Authorization Non-interventional German sAfety study of GilEnyA (PANGAEA) to assess prospectively baseline characteristics and outcomes after 12 months (± 90 days) of fingolimod treatment. Patients were divided into 2 cohorts: fingolimod starter [first received fingolimod in PANGAEA (n = 3315)] and previous study [received fingolimod before enrollment in PANGAEA in RCTs (n = 875), some of whom also had baseline data at entry into RCTs (n = 505)]. At PANGAEA baseline, patients in the fingolimod starter versus the previous study cohort had a higher annualized relapse rate [ARR (95% confidence interval): 1.79 (1.75-1.83) vs 1.32 (1.25-1.40)] and Expanded Disability Status Scale score [3.11 (3.04-3.17) vs 2.55 (2.44-2.66)]. A greater proportion in the fingolimod starter versus previous study cohort had diabetes (2.0% vs 0.7%). After 12 months of fingolimod, ARRs were lower than in the 12 months before PANGAEA enrollment in the fingolimod starter [0.386 (0.360-0.414)] and previous study [0.276 (0.238-0.320)] cohorts. Expanded Disability Status Scale scores were stable versus baseline. Adverse events were experienced by similar proportions in both cohorts during fingolimod treatment. Relevant differences exist in disease activity and comorbidities between patients receiving fingolimod in clinical practice versus RCTs. Irrespective of baseline differences indicating a higher proportion at an advanced stage of multiple sclerosis in the real world versus RCTs, fingolimod remains effective, with a manageable safety profile.

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.

Changes in cohort wealth over a generation.

PubMed

David, M H; Menchik, P L

1988-08-01

Empirical computation of expected wealth is hampered by two problems: mortality risks vary in the population and over time; and observation of net estates for most cohorts is truncated, as some individuals in a cohort survive the calendar date on which observation is terminated. These two problems are solved in estimating cohort wealth for a sample of Wisconsin taxpayers. Hazard rate models of differential occupational mortality risks were estimated from the occupational information on the tax records. Values of net estate are simulated for individuals in each birth cohort who survived. Survivors have characteristics that imply greater wealth holdings than the deceased in every birth year covered by the study (1890-1924). Because of this, estimates of wealth-age relationships produced by the estate multiplier method for any given year will have a serious downward bias. Longitudinal data imply that dissaving does not occur after age 65.

A cohort mortality and cancer incidence survey of recent entrants (1982-91) to the UK rubber industry: findings for 1983-2004.

PubMed

Dost, Abid; Straughan, Jk; Sorahan, Tom

2007-05-01

To monitor the occurrence of cancer in a recently defined cohort of UK rubber workers. A cohort of 8651 male and female workers from 41 UK rubber factories has been enumerated. All employees had a minimum of 12 months employment and were first employed at one of the participating factories in the period 1982-91. Mortality and cancer incidence data for the period 1983-2004 were compared with expected values based on appropriate national rates. Mortality from lung cancer was close to expectation for males [observed 22, standardized mortality ratio (SMR) 93] and females (observed 2, SMR 70). Mortality from stomach cancer was also unexceptional in males (observed 4, SMR 86) and females (observed 0, SMR 0). Although based on small numbers, significantly elevated mortality was shown for multiple myeloma in males (observed 5, SMR 385) and females (observed 2, SMR 952). All seven of these latter deaths occurred in workers from the general rubber goods (GRG) sector. The findings should be treated with caution as they relate to a relatively early period of follow-up. Nevertheless, they hold out the prospect that the elevated SMRs for stomach and lung cancers reported for historical cohorts of UK rubber workers will not be present in more recent cohorts. The elevated occurrence of multiple myeloma may represent no more than a chance finding. Alternatively, these findings may reflect the presence of an unrecognized occupational cancer hazard in parts of the GRG sector of the UK rubber industry.

Cosmetic talc as a risk factor for pleural mesothelioma: a weight of evidence evaluation of the epidemiology.

PubMed

Finley, Brent L; Benson, Stacey M; Marsh, Gary M

2017-03-01

Due to some historical (and inaccurate) reports that asbestos might be present in some cosmetic talc products, questions are occasionally raised regarding the potential pleural mesothelioma risks associated with cosmetic talc products. Our objective was to determine the incidence of pleural mesothelioma of individuals exposed to cosmetic talc. We conducted a systematic review of the epidemiological literature for cosmetic talc miners and millers and found three occupational cohort studies that evaluated pleural mesothelioma incidence in workers in Italy, Norway, France, and Austria. We conducted a second literature review to evaluate the incidence and mortality of pleural mesothelioma among patients who received talc pleurodesis treatments before 1965 and found retrospective clinical studies including over 300 patients with follow-up ranging from 14 to 40 years. There were no mesotheliomas reported in any of the cosmetic talc miner and miller cohorts. A pooled analysis of data from the cohort mortality studies indicated that four mesothelioma deaths would have been expected from the 90,022 person-years of observation, and this was associated with 84% and 67% statistical power to observe a 3-fold or 2.5-fold increase in pleural mesothelioma mortality, respectively. None of the patients who received talc pleurodesis treatments developed mesothelioma. We conclude that there is no epidemiological evidence to support the hypothesis that exposure to cosmetic talc is associated with the development of pleural mesothelioma.

Prenatal Exposure to Acetaminophen and Risk for Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorder: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Cohort Studies.

PubMed

Masarwa, Reem; Levine, Hagai; Gorelik, Einat; Reif, Shimon; Perlman, Amichai; Matok, Ilan

2018-04-24

Acetaminophen is the most commonly used analgesic and antipyretic during pregnancy. Evidence of neuro-disruptive properties is accumulating. Therefore, we sought to evaluate the risk for attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD) in the offspring of women exposed to acetaminophen during pregnancy. We searched MEDLINE, EMBASE, and Cochrane up to January 2017. Data were independently extracted and assessed by two researchers. Seven eligible retrospective cohorts included 132,738 mother and child pairs and with a follow-up period of 3-11 years. Pooled risk ratio (RR) for ADHD was (RR=1.32, 95% CI 1.18,1.45, I2=61%), for ASD (RR=1.23, 95% CI1.13,1.32, I2=17%), and for hyperactivity symptoms (RR=1.23, 95% CI 1.01,1.49, I2=94%). In meta-regression analysis, the association between exposure and ADHD increased with childs' age upon follow-up and with the mean duration of exposure (β=0.0354, 95% CI 0.001,0.07), (β=0.006, 95% CI 0.009,0.01). The available data is of observational nature only. Studies differed gravely in exposure and outcome assessment. Acetaminophen use during pregnancy is associated with an increased risk for ADHD, ASD and hyperactivity symptoms. These findings are concerning, however, results should be interpreted with caution as the available evidence consists of observational studies and susceptible to several potential sources of bias.

Impact of a Health Management Program on Healthcare Outcomes among Patients on Augmentation Therapy for Alpha 1-Antitrypsin Deficiency: An Insurance Claims Analysis.

PubMed

Campos, Michael A; Runken, Michael C; Davis, Angela M; Johnson, Michael P; Stone, Glenda A; Buikema, Ami R

2018-04-01

Alpha 1-antitrypsin deficiency (AATD) is a genetic disorder which reduces serum alpha 1-antitrypsin (AAT or alpha1-proteinase inhibitor, A1PI) and increases the risk of chronic obstructive pulmonary disease (COPD). Management strategies include intravenous A1PI augmentation, and, in some cases, a health management program (Prolastin Direct ® ; PD). This study compared clinical and economic outcomes between patients with and without PD program participation. This retrospective study included commercial and Medicare Advantage health insurance plan members with ≥ 1 claim with diagnosis codes for COPD and ≥ 1 medical or pharmacy claim including A1PI (on index date). Outcomes were compared between patients receiving only Prolastin ® or Prolastin ® -C (PD cohort) and patients who received a different brand without PD (Comparator cohort). Demographic and clinical characteristics were captured during 6 months pre-index. Post-index exacerbation episodes and healthcare utilization and costs were compared between cohorts. The study sample comprised 445 patients (n = 213 in PD cohort; n = 232 in Comparator cohort), with a mean age 55.5 years, 50.8% male, and 78.9% commercially insured. The average follow-up was 822 days (2.25 years), and the average time on A1PI was 747 days (2.04 years). Few differences were observed in demographic or clinical characteristics. Adjusting for differences in patient characteristics, the rate of severe exacerbation episodes was reduced by 36.1% in the PD cohort. Adjusted total annual all-cause costs were 11.4% lower, and adjusted mean respiratory-related costs were 10.6% lower in the PD cohort than the Comparator cohort. Annual savings in all-cause total costs in the PD cohort relative to the Comparator cohort was US$25,529 per patient, largely due to significantly fewer and shorter hospitalizations. These results suggest that comprehensive health management services may improve both clinical and economic outcomes among patients with COPD and AATD who receive augmentation therapy. Grifols Shared Services of North America, Inc.

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.

Occupational variation in incidence of bladder cancer: a comparison of population-representative cohorts from Nordic countries and Canada.

PubMed

Hadkhale, Kishor; MacLeod, Jill; Demers, Paul A; Martinsen, Jan Ivar; Weiderpass, Elisabete; Kjaerheim, Kristina; Lynge, Elsebeth; Sparen, Pär; Tryggvadottir, Laufey; Anne Harris, M; Tjepkema, Michael; Peters, Paul A; Pukkala, Eero

2017-08-04

The objective of this study was to compare occupational variation of the risk of bladder cancer in the Nordic countries and Canada. In the Nordic Occupational Cancer study (NOCCA), 73 653 bladder cancer cases were observed during follow-up of 141.6 million person-years. In the Canadian Census Health and Environment Cohort (CanCHEC), 8170 cases were observed during the follow-up of 36.7 million person-years. Standardised incidence ratios with 95% CI were estimated for 53 occupations in the NOCCA cohort and HR with 95% CIs were estimated for 42 occupations in the CanCHEC. Elevated risks of bladder cancer were observed among hairdressers, printers, sales workers, plumbers, painters, miners and laundry workers. Teachers and agricultural workers had reduced risk of bladder cancer in both cohorts. Chimney-sweeps, tobacco workers and waiters had about 1.5-fold risk in the Nordic countries; no risk estimates for these categories were given from the CanCHEC cohort. We observed different occupational patterns in risk of bladder cancer in Nordic countries and Canada. The only occupation with similarly increased risk was observed among sales workers. Differences in smoking across occupational groups may explain some, but not all, of this variation. © 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.

Whole-Exome Sequencing in Familial Parkinson Disease

PubMed Central

Farlow, Janice L.; Robak, Laurie A.; Hetrick, Kurt; Bowling, Kevin; Boerwinkle, Eric; Coban-Akdemir, Zeynep H.; Gambin, Tomasz; Gibbs, Richard A.; Gu, Shen; Jain, Preti; Jankovic, Joseph; Jhangiani, Shalini; Kaw, Kaveeta; Lai, Dongbing; Lin, Hai; Ling, Hua; Liu, Yunlong; Lupski, James R.; Muzny, Donna; Porter, Paula; Pugh, Elizabeth; White, Janson; Doheny, Kimberly; Myers, Richard M.; Shulman, Joshua M.; Foroud, Tatiana

2016-01-01

IMPORTANCE Parkinson disease (PD) is a progressive neurodegenerative disease for which susceptibility is linked to genetic and environmental risk factors. OBJECTIVE To identify genetic variants contributing to disease risk in familial PD. DESIGN, SETTING, AND PARTICIPANTS A 2-stage study design that included a discovery cohort of families with PD and a replication cohort of familial probands was used. In the discovery cohort, rare exonic variants that segregated in multiple affected individuals in a family and were predicted to be conserved or damaging were retained. Genes with retained variants were prioritized if expressed in the brain and located within PD-relevant pathways. Genes in which prioritized variants were observed in at least 4 families were selected as candidate genes for replication in the replication cohort. The setting was among individuals with familial PD enrolled from academic movement disorder specialty clinics across the United States. All participants had a family history of PD. MAIN OUTCOMES AND MEASURES Identification of genes containing rare, likely deleterious, genetic variants in individuals with familial PD using a 2-stage exome sequencing study design. RESULTS The 93 individuals from 32 families in the discovery cohort (49.5% [46 of 93] female) had a mean (SD) age at onset of 61.8 (10.0) years. The 49 individuals with familial PD in the replication cohort (32.6% [16 of 49] female) had a mean (SD) age at onset of 50.1 (15.7) years. Discovery cohort recruitment dates were 1999 to 2009, and replication cohort recruitment dates were 2003 to 2014. Data analysis dates were 2011 to 2015. Three genes containing a total of 13 rare and potentially damaging variants were prioritized in the discovery cohort. Two of these genes (TNK2 and TNR) also had rare variants that were predicted to be damaging in the replication cohort. All 9 variants identified in the 2 replicated genes in 12 families across the discovery and replication cohorts were confirmed via Sanger sequencing. CONCLUSIONS AND RELEVANCE TNK2 and TNR harbored rare, likely deleterious, variants in individuals having familial PD, with similar findings in an independent cohort. To our knowledge, these genes have not been previously associated with PD, although they have been linked to critical neuronal functions. Further studies are required to confirm a potential role for these genes in the pathogenesis of PD. PMID:26595808

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.

Negative Control Outcomes and the Analysis of Standardized Mortality Ratios.

PubMed

Richardson, David B; Keil, Alexander P; Tchetgen Tchetgen, Eric; Cooper, Glinda

2015-09-01

In occupational cohort mortality studies, epidemiologists often compare the observed number of deaths in the cohort to the expected number obtained by multiplying person-time accrued in the study cohort by the mortality rate in an external reference population. Interpretation of the result may be difficult due to noncomparability of the occupational cohort and reference population with respect to unmeasured risk factors for the outcome of interest. We describe an approach to estimate an adjusted standardized mortality ratio (aSMR) to control for such bias. The approach draws on methods developed for the use of negative control outcomes. Conditions necessary for unbiased estimation are described, as well as looser conditions necessary for bias reduction. The approach is illustrated using data on bladder cancer mortality among male Oak Ridge National Laboratory workers. The SMR for bladder cancer was elevated among hourly-paid males (SMR = 1.9; 95% confidence interval [CI] = 1.3, 2.7) but not among monthly-paid males (SMR = 1.0; 95% CI = 0.67, 1.3). After indirect adjustment using the proposed approach, the mortality ratios were similar in magnitude among hourly- and monthly-paid men (aSMR = 2.2; 95% CI = 1.5, 3.2; and, aSMR = 2.0; 95% CI = 1.4, 2.8, respectively). The proposed adjusted SMR offers a complement to typical SMR analyses.

Long-term results from the Contura multilumen balloon breast brachytherapy catheter phase 4 registry trial.

PubMed

Cuttino, Laurie W; Arthur, Douglas W; Vicini, Frank; Todor, Dorin; Julian, Thomas; Mukhopadhyay, Nitai

2014-12-01

To describe the long-term outcomes from a completed, multi-institutional phase 4 registry trial using the Contura multilumen balloon (CMLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer. Three hundred forty-two evaluable patients were enrolled by 23 institutions between January 2008 and February 2011. All patients received 34 Gy in 10 fractions, delivered twice daily. Rigorous target coverage and normal tissue dose constraints were observed. The median follow-up time was 36 months (range, 1-54 months). For the entire patient cohort of 342 patients, 10 patients experienced an ipsilateral breast tumor recurrence (IBTR). Eight of these IBTR were classified as true recurrences/marginal miss (TRMM), and 2 were elsewhere failures (EF). Local recurrence-free survival was 97.8% at 3 years. For the entire cohort, 88% of patients had good to excellent overall cosmesis. The overall incidence of infection was 8.5%. Symptomatic seroma was reported in only 4.4% of patients. A separate analysis was performed to determine whether improved outcomes would be observed for patients treated at high-volume centers with extensive brachytherapy experience. Three IBTR were observed in this cohort, only 1 of which was classified as a TRMM. Local recurrence-free survival at high-volume centers was 98.1% at 3 years. Overall cosmetic outcome and toxicity were superior in patients treated at high-volume centers. In these patients, 95% had good to excellent overall cosmesis. Infection was observed in only 2.9% of patients, and symptomatic seroma was reported in only 1.9%. Use of the CMLB for APBI delivery is associated with acceptable long-term local control and toxicity. Local recurrence-free survival was 97.8% at 3 years. Significant (grade 3) toxicity was uncommon, and no grade 4 toxicity was observed. Treatment at high-volume centers was associated with decreased late toxicity. Copyright © 2014 Elsevier Inc. All rights reserved.

Long-Term Results From the Contura Multilumen Balloon Breast Brachytherapy Catheter Phase 4 Registry Trial

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

Cuttino, Laurie W., E-mail: lcuttino@mcvh-vcu.edu; Arthur, Douglas W.; Vicini, Frank

2014-12-01

Purpose: To describe the long-term outcomes from a completed, multi-institutional phase 4 registry trial using the Contura multilumen balloon (CMLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer. Methods and Materials: Three hundred forty-two evaluable patients were enrolled by 23 institutions between January 2008 and February 2011. All patients received 34 Gy in 10 fractions, delivered twice daily. Rigorous target coverage and normal tissue dose constraints were observed. Results: The median follow-up time was 36 months (range, 1-54 months). For the entire patient cohort of 342 patients, 10 patients experienced an ipsilateral breast tumor recurrencemore » (IBTR). Eight of these IBTR were classified as true recurrences/marginal miss (TRMM), and 2 were elsewhere failures (EF). Local recurrence-free survival was 97.8% at 3 years. For the entire cohort, 88% of patients had good to excellent overall cosmesis. The overall incidence of infection was 8.5%. Symptomatic seroma was reported in only 4.4% of patients. A separate analysis was performed to determine whether improved outcomes would be observed for patients treated at high-volume centers with extensive brachytherapy experience. Three IBTR were observed in this cohort, only 1 of which was classified as a TRMM. Local recurrence-free survival at high-volume centers was 98.1% at 3 years. Overall cosmetic outcome and toxicity were superior in patients treated at high-volume centers. In these patients, 95% had good to excellent overall cosmesis. Infection was observed in only 2.9% of patients, and symptomatic seroma was reported in only 1.9%. Conclusion: Use of the CMLB for APBI delivery is associated with acceptable long-term local control and toxicity. Local recurrence-free survival was 97.8% at 3 years. Significant (grade 3) toxicity was uncommon, and no grade 4 toxicity was observed. Treatment at high-volume centers was associated with decreased late toxicity.« less

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…

Analysis of air pollution mortality in terms of life expectancy changes: relation between time series, intervention, and cohort studies.

PubMed

Rabl, Ari

2006-02-01

Information on life expectancy change is of great concern for policy makers, as evidenced by the discussions of the so-called "harvesting" issue (i.e. the question being, how large a loss each death corresponds to in the mortality results of time series studies). Whereas most epidemiological studies of air pollution mortality have been formulated in terms of mortality risk, this paper shows that a formulation in terms of life expectancy change is mathematically equivalent, but offers several advantages: it automatically takes into account the constraint that everybody dies exactly once, regardless of pollution; it provides a unified framework for time series, intervention studies and cohort studies; and in time series and intervention studies, it yields the life expectancy change directly as a time integral of the observed mortality rate. Results are presented for life expectancy change in time series studies. Determination of the corresponding total number of attributable deaths (as opposed to the number of observed deaths) is shown to be problematic. The time variation of mortality after a change in exposure is shown to depend on the processes by which the body can repair air pollution damage, in particular on their time constants. Hypothetical results are presented for repair models that are plausible in view of the available intervention studies of air pollution and of smoking cessation. If these repair models can also be assumed for acute effects, the results of cohort studies are compatible with those of time series. The proposed life expectancy framework provides information on the life expectancy change in time series studies, and it clarifies the relation between the results of time series, intervention, and cohort studies.

Time trends for prostate cancer mortality in Brazil and its geographic regions: An age-period-cohort analysis.

PubMed

Braga, Sonia Faria Mendes; de Souza, Mirian Carvalho; Cherchiglia, Mariangela Leal

2017-10-01

In the 1980s, an increase in mortality rates for prostate cancer was observed in North America and developed European countries. In the 1990s, however, mortality rates decreased for these countries, an outcome related to early detection of the disease. Conversely, an upward trend in mortality rates was observed in Brazil. This study describe the trends in mortality for prostate cancer in Brazil and geographic regions (North, Northeast, South, Southeast, and Central-West) between 1980 until 2014 and analyze the influence of age, period, and cohort effects on mortality rates. This time-series study used data from the Mortality Information System (SIM) and population data from Brazilian Institute for Geography and Statistics (IBGE). The effects on mortality rates were examined using age-period-cohort (APC) models. Crude and standardized mortality rates showed an upward trend for Brazil and its regions more than 2-fold the last 30 years. Age effects showed an increased risk of death in all regions. Period effects showed a higher risk of death in the finals periods for the North and Northeast. Cohort effects showed risk of death was higher for younger than older generations in Brazil and regions, mainly Northeast (RR Adjusted =3.12, 95% CI 1.29-1.41; RR Adjusted =0.28, 95% CI 0.26-0.30, respectively). The increase in prostate cancer mortality rates in Brazil and its regions was mainly due to population aging. The differences in mortality rates and APC effects between regions are related to demographic differences and access of health services across the country. Copyright © 2017 Elsevier Ltd. All rights reserved.

Patterns of circulating fat-soluble vitamins and carotenoids and risk of frailty in four European cohorts of older adults.

PubMed

Pilleron, Sophie; Weber, Daniela; Pérès, Karine; Colpo, Marco; Gomez-Cabrero, David; Stuetz, Wolfgang; Dartigues, Jean-François; Ferrucci, Luigi; Bandinelli, Stefania; Garcia-Garcia, Francisco Jose; Grune, Tilman; Féart, Catherine

2018-01-27

To investigate the cross-sectional and prospective associations between patterns of serum fat-soluble micronutrients and frailty in four European cohorts of older adults 65 years of age and older. Participants from the Three-City (Bordeaux, France), AMI (Gironde, France), TSHA (Toledo, Spain) and InCHIANTI (Tuscany, Italy) cohorts with available data on serum α-carotene, β-carotene, lycopene, cryptoxanthin, lutein + zeaxanthin, retinol, α-tocopherol, γ-tocopherol and 25-hydroxyvitamin D3 (25(OH)D) were included. A principal component (PC) analysis was used to derive micronutrient patterns. Frailty was defined using Fried's criteria. Multivariate logistic regression models adjusted for socio-demographic and health-related covariates were performed to assess the association between micronutrient patterns and prevalent frailty in 1324 participants, and the risk of frailty in 915 initially non-frail participants. Three different patterns were identified: the first pattern was characterized by higher serum carotenoids and α-tocopherol levels; the second was characterized by high loadings for serum vitamins A and E levels and low loadings for carotenes level; the third one had the highest loading for serum 25(OH)D and cryptoxanthin level and the lowest loading for vitamin A and E. A significant cross-sectional association was only observed between the seconnd PC and prevalent frailty (p = 0.02). Compared to the highest quartile, participants in the lowest quartile-i.e., high carotenes and low vitamins E and A levels-had higher odds of frailty (Odds ratio = 2.2; 95% confidence interval 1.3-3.8). No association with the risk of frailty was observed. These findings suggest that some specific micronutrient patterns are markers but not predictors of frailty in these European cohorts of older adults.

Risk factors for lung function decline in a large cohort of young cystic fibrosis patients.

PubMed

Cogen, Jonathan; Emerson, Julia; Sanders, Don B; Ren, Clement; Schechter, Michael S; Gibson, Ronald L; Morgan, Wayne; Rosenfeld, Margaret

2015-08-01

To identify novel risk factors and corroborate previously identified risk factors for mean annual decline in FEV1% predicted in a large, contemporary, United States cohort of young cystic fibrosis (CF) patients. Retrospective observational study of participants in the EPIC Observational Study, who were Pseudomonas-negative and ≤12 years of age at enrollment in 2004-2006. The associations between potential demographic, clinical, and environmental risk factors evaluated during the baseline year and subsequent mean annual decline in FEV1 percent predicted were evaluated using generalized estimating equations. The 946 participants in the current analysis were followed for a mean of 6.2 (SD 1.3) years. Mean annual decline in FEV1% predicted was 1.01% (95%CI 0.85-1.17%). Children with one or no F508del mutations had a significantly smaller annual decline in FEV1 compared to F508del homozygotes. In a multivariable model, risk factors during the baseline year associated with a larger subsequent mean annual lung function decline included female gender, frequent or productive cough, low BMI (<66th percentile, median in the cohort), ≥1 pulmonary exacerbation, high FEV1 (≥115% predicted, in the top quartile), and respiratory culture positive for methicillin-sensitive Staphylococcus aureus, methicillin-resistant S. aureus, or Stenotrophomonas maltophilia. We have identified a range of risk factors for FEV1 decline in a large cohort of young, CF patients who were Pa negative at enrollment, including novel as well as previously identified characteristics. These results could inform the design of a clinical trial in which rate of FEV1 decline is the primary endpoint and identify high-risk groups that may benefit from closer monitoring. © 2015 Wiley Periodicals, Inc.

Measuring trends in age at first sex and age at marriage in Manicaland, Zimbabwe.

PubMed

Cremin, I; Mushati, P; Hallett, T; Mupambireyi, Z; Nyamukapa, C; Garnett, G P; Gregson, S

2009-04-01

To identify reporting biases and to determine the influence of inconsistent reporting on observed trends in the timing of age at first sex and age at marriage. Longitudinal data from three rounds of a population-based cohort in eastern Zimbabwe were analysed. Reports of age at first sex and age at marriage from 6837 individuals attending multiple rounds were classified according to consistency. Survival analysis was used to identify trends in the timing of first sex and marriage. In this population, women initiate sex and enter marriage at younger ages than men but spend much less time between first sex and marriage. Among those surveyed between 1998 and 2005, median ages at first sex and first marriage were 18.5 years and 21.4 years for men and 18.2 years and 18.5 years, respectively, for women aged 15-54 years. High levels of reports of both age at first sex and age at marriage among those attending multiple surveys were found to be unreliable. Excluding reports identified as unreliable from these analyses did not alter the observed trends in either age at first sex or age at marriage. Tracing birth cohorts as they aged revealed reporting biases, particularly among the youngest cohorts. Comparisons by birth cohorts, which span a period of >40 years, indicate that median age at first sex has remained constant over time for women but has declined gradually for men. Although many reports of age at first sex and age at marriage were found to be unreliable, inclusion of such reports did not result in artificial generation or suppression of trends.

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.

Quantitative Assessment of Knee Progression Angle During Gait in Children With Cerebral Palsy.

PubMed

Davids, Jon R; Cung, Nina Q; Pomeroy, Robin; Schultz, Brooke; Torburn, Leslie; Kulkarni, Vedant A; Brown, Sean; Bagley, Anita M

2018-04-01

Abnormal hip rotation is a common deviation in children with cerebral palsy (CP). Clinicians typically assess hip rotation during gait by observing the direction that the patella points relative to the path of walking, which is referred to as the knee progression angle (KPA). Two kinematic methods for calculating the KPA are compared with each other. Video-based qualitative assessment of KPA is compared with the quantitative methods to determine reliability and validity. The KPA was calculated by both direct and indirect methods for 32 typically developing (TD) children and a convenience cohort of 43 children with hemiplegic type CP. An additional convenience cohort of 26 children with hemiplegic type CP was selected for qualitative assessment of KPA, performed by 3 experienced clinicians, using 3 categories (internal, >10 degrees; neutral, -10 to 10 degrees; and external, >-10 degrees). Root mean square (RMS) analysis comparing the direct and indirect KPAs was 1.14+0.43 degrees for TD children, and 1.75+1.54 degrees for the affected side of children with CP. The difference in RMS among the 2 groups was statistically, but not clinically, significant (P=0.019). Intraclass correlation coefficient revealed excellent agreement between the direct and indirect methods of KPA for TD and CP children (0.996 and 0.992, respectively; P<0.001).For the qualitative assessment of KPA there was complete agreement among all examiners for 17 of 26 cases (65%). Direct KPA matched for 49 of 78 observations (63%) and indirect KPA matched for 52 of 78 observations (67%). The RMS analysis of direct and indirect methods for KPA was statistically but not clinically significant, which supports the use of either method based upon availability. Video-based qualitative assessment of KPA showed moderate reliability and validity. The differences between observed and calculated KPA indicate the need for caution when relying on visual assessments for clinical interpretation, and demonstrate the value of adding KPA calculation to standard kinematic analysis. Level II-diagnostic test.

Relationship between artificially sweetened and sugar-sweetened cola beverage consumption during pregnancy and preterm delivery in a multi-ethnic cohort: analysis of the Born in Bradford cohort study.

PubMed

Petherick, E S; Goran, M I; Wright, J

2014-03-01

The aim of this study was to investigate the relationship between the intake of sugar-sweetened (SS) and artificially sweetened (AS) cola beverages during pregnancy and the risk of preterm delivery (PTD). At baseline (2007-2010), 8914 pregnant women were recruited to the Born in Bradford birth cohort study at 24-28 weeks of pregnancy. Women completed a questionnaire describing their health and lifestyle behaviours, including their consumption of AS and SS cola beverages reported as cups per day, which were then linked to maternity records. The relationship between SS and AS cola beverage consumption was examined using logistic regression analyses. No relationship was observed between daily AS cola beverage consumption and PTD. Women who drank four cups per day of SS cola beverages had higher odds of a PTD when compared with women who did not consume these beverages daily. We conclude that high daily consumption of SS cola beverages during pregnancy is associated with increases in the rate of PTD.

Index pregnancy versus post-index pregnancy in patients with recurrent pregnancy loss.

PubMed

Greenberg, Tzlil; Tzivian, Liliana; Harlev, Avi; Serjienko, Ruslan; Mazor, Moshe; Bashiri, Asher

2015-01-01

To compare pregnancy outcomes of two consecutive pregnancies in a cohort of women with recurrent pregnancy loss (RPL), in order to determine the long-term prognosis of women with RPL managed in a dedicated RPL clinic. A retrospective cohort study including 262 patients with two or more consecutive pregnancy losses followed by two subsequent pregnancies--index pregnancy (IP) and post-index pregnancy (PIP). All patients were evaluated and treated in the RPL clinic in the Soroka University Medical Center. Comparing IP with PIP, no significant difference in perinatal outcome was observed. The perinatal outcome remained encouraging with approximately 73% birth rate (73.7% versus 72.5%; p=0.83). Only 11% of the women with RPL continued to experience pregnancy losses for two subsequent pregnancies. In a multivariate logistic regression analysis, number of miscarriages pre-Index was the only factor independently associated with birth in the PIP. There is no significant difference between IP and PIP regarding perinatal outcome. Appropriate management in the RPL clinic conferred a significant beneficial effect on long-term pregnancy outcome of a cohort of women with RPL.

WAERS: an application for Web-assisted estimation of relative survival.

PubMed

Clèries, Ramon; Valls, Joan; Esteban, Laura; Gálvez, Jordi; Pareja, Laura; Sanz, Xavier; Alliste, Luisa; Martínez, José Miguel; Moreno, Víctor; Bosch, Xavier; Borràs, Josep Maria; Ribes, Josepa Maria

2007-09-01

Net cancer survival estimation is usually performed by computing relative survival (RS), which is defined as the ratio between observed and expected survival rates. The mortality of a reference population is required in order to compute the expected survival rate, which can be performed using a variety of statistical packages. A new Web interface to compute RS, called WAERS, has been developed by the Catalan Institute of Oncology. The reference population is first selected, and then the RS of a cohort is computed. A remote server is used for this purpose. A mock example serves to illustrate the use of the tool with a hypothetical cohort, for which RS is estimated based on three different reference populations (a province of Spain, an autonomous community (Region), and the entire Spanish population). At present, only mortality tables for different areas of Spain are available. Future improvements of this application will include mortality tables of Latin American and European Union countries, and stratified (control variable) analysis. This application can be also useful for cohort mortality studies and for registries of several diseases.

Haemoglobinuria is associated with chronic kidney disease and its progression in patients with sickle cell anaemia

PubMed Central

Saraf, Santosh L.; Zhang, Xu; Kanias, Tamir; Lash, James P.; Molokie, Robert E.; Oza, Bharvi; Lai, Catherine; Rowe, Julie H.; Gowhari, Michel; Hassan, Johara; DeSimone, Joseph; Machado, Roberto F.; Gladwin, Mark T.; Little, Jane A.; Gordeuk, Victor R.

2014-01-01

Summary To evaluate the association between haemoglobinuria and chronic kidney disease (CKD) in sickle cell anaemia (SCA), we analysed 356 adult haemoglobin SS or Sβ° thalassaemia patients from the University of Illinois at Chicago (UIC) and 439 from the multi-centre Walk-Treatment of Pulmonary Hypertension and Sickle Cell Disease with Sildenafil Therapy (PHaSST) cohort. CKD was classified according to National Kidney Foundation Kidney Disease Outcomes Quality Initiatives guidelines. Haemoglobinuria, defined as positive haem on urine dipstick with absent red blood cells on microscopy, was confirmed by enzyme-linked immunosorbent assay in a subset of patients. The prevalence of CKD was 58% in the UIC cohort and 54% in the Walk-PHaSST cohort, and haemoglobinuria was observed in 36% and 20% of the patients, respectively. Pathway analysis in both cohorts indicated an independent association of lactate dehydrogenase with haemoglobinuria and, in turn, independent associations of haemoglobinuria and age with CKD (P<0.0001). After a median of 32 months of follow-up in the UIC cohort, haemoglobinuria was associated with progression of CKD (halving of estimated glomerular filtration rate or requirement for dialysis; Hazard ratio [HR] 13.9, 95% confidence interval [CI] 1.7-113.2, P=0.0012) and increasing albuminuria (HR 3.1, 95% CI: 1.3-7.7; logrank P=0.0035). In conclusion haemoglobinuria is common in SCA and is associated with CKD, consistent with a role for intravascular haemolysis in the pathogenesis of renal dysfunction in SCA. PMID:24329963

Age, Period, and Cohort Effects on Mortality From Ischemic Heart Disease in Southern Spain.

PubMed

Ocaña-Riola, Ricardo; Mayoral-Cortés, José María; Fernández-Ajuria, Alberto; Sánchez-Cantalejo, Carmen; Martín-Olmedo, Piedad; Blanco-Reina, Encarnación

2015-05-01

Ischemic heart disease is the leading cause of death and one of the top 4 causes of burden of disease worldwide. The aim of this study was to evaluate age-period-cohort effects on mortality from ischemic heart disease in Andalusia (southern Spain) and in each of its 8 provinces during the period 1981-2008. A population-based ecological study was conducted. In all, 145 539 deaths from ischemic heart disease were analyzed for individuals aged between 30 and 84 years who died in Andalusia in the study period. A nonlinear regression model was estimated for each sex and geographical area using spline functions. There was an upward trend in male and female mortality rate by age from the age of 30 years. The risk of death for men and women showed a downward trend for cohorts born after 1920, decreasing after 1960 with a steep slope among men. Analysis of the period effect showed that male and female death risk first remained steady from 1981 to 1990 and then increased between 1990 and 2000, only to decrease again until 2008. There were similar age-period-cohort effects on mortality in all the provinces of Andalusia and for Andalusia as a whole. If the observed cohort and period effects persist, male and female mortality from ischemic heart disease will continue to decline. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Changing rates of adenocarcinoma and adenosquamous carcinoma of the cervix in England.

PubMed

Sasieni, P; Adams, J

2001-05-12

A recent analysis showed little or no effect of screening on the incidence of adenocarcinoma of the cervix between 1971 and 1992. We have used additional data on cancers diagnosed in 1993-94 in England and up to 1997 in five English cancer registries to investigate more recent trends. After inputing the number of adenocarcinomas in women with unknown histology, we fitted an age-cohort model to 8062 adenocarcinomas of the cervix diagnosed in England between 1971 and 1987. Predictions from this model were applied to the more recent data on 5854 cases. Residual effects were plotted against year of diagnosis in each of four age-groups. We estimated the underlying risk of cervical adenocarcinoma to be 14 times (95% CI 11-19) greater in women born in the early 1960s than in cohorts born before 1935. An age-cohort model fitted the data for England well up to 1987, but substantially overestimated the numbers of adenocarcinomas in young women from 1990 onwards. In 1996-97 the incidence rate in women aged 25-54 years was less than 40% of that predicted from the age-cohort model. The substantial increase in cervical adenocarcinoma in recent years is largely a birth-cohort effect presumably associated with greater exposure to human papillomavirus after the sexual revolution in the 1960s. The relative decline in younger women observed in more recent years suggests an effect of cervical screening.

Anthrax vaccine adsorbed: further evidence supporting continuing the vaccination series rather than restarting the series when doses are delayed.

PubMed

Pittman, Phillip R; Cavicchia, M A; Kingsbury, J L; Johnson, N A; Barrera-Oro, J G; Schmader, T; Korman, L; Quinn, X; Ranadive, M

2014-09-03

Whether to restart or continue the series when anthrax vaccine doses are missed is a frequent medical management problem. We applied the noninferiority analysis model to this prospective study comparing the Bacillus anthracis protective antigen (PA) IgG antibody response and lethal toxin neutralization activity at day 28 to the anthrax vaccine adsorbed (AVA) (Biothrax®) administered on schedule or delayed. A total of 600 volunteers were enrolled: 354 in the on-schedule cohort; 246 in the delayed cohort. Differences were noted in immune responses between cohorts (p<0.0001) and among the racial categories (p<0.0001). Controlling for covariates, the delayed cohort was non-inferior to the on-schedule cohort for the rate of 4-fold rise in both anti-PA IgG concentration (p<0.0001) and TNA ED50 titers (p<0.0001); as well as the mean log10-transformed anti-PA IgG concentration (p<0.0001) and the mean log10-transformed TNA ED50 titers (p<0.0001). Providing a missed AVA dose after a delay as long as 5-7 years, elicits anti-PA IgG antibody and TNA ED50 responses that are robust and non-inferior to the responses observed when the 6-month dose is given on-schedule. These important data suggest it is not necessary to restart the series when doses of the anthrax vaccine are delayed as long as 5 or more years. Published by Elsevier Ltd.

Assessment of Gene-by-Sex Interaction Effect on Bone Mineral Density

PubMed Central

Liu, Ching-Ti; Estrada, Karol; Yerges-Armstrong, Laura M.; Amin, Najaf; Evangelou, Evangelos; Li, Guo; Minster, Ryan L.; Carless, Melanie A.; Kammerer, Candace M.; Oei, Ling; Zhou, Yanhua; Alonso, Nerea; Dailiana, Zoe; Eriksson, Joel; García-Giralt, Natalia; Giroux, Sylvie; Husted, Lise Bjerre; Khusainova, Rita I.; Koromila, Theodora; Kung, Annie WaiChee; Lewis, Joshua R.; Masi, Laura; Mencej-Bedrac, Simona; Nogues, Xavier; Patel, Millan S.; Prezelj, Janez; Richards, J Brent; Sham, Pak Chung; Spector, Timothy; Vandenput, Liesbeth; Xiao, Su-Mei; Zheng, Hou-Feng; Zhu, Kun; Balcells, Susana; Brandi, Maria Luisa; Frost, Morten; Goltzman, David; González-Macías, Jesús; Karlsson, Magnus; Khusnutdinova, Elza K.; Kollia, Panagoula; Langdahl, Bente Lomholt; Ljunggren, Östen; Lorentzon, Mattias; Marc, Janja; Mellström, Dan; Ohlsson, Claes; Olmos, José M.; Ralston, Stuart H.; Riancho, José A.; Rousseau, François; Urreizti, Roser; Van Hul, Wim; Zarrabeitia, María T.; Castano-Betancourt, Martha; Demissie, Serkalem; Grundberg, Elin; Herrera, Lizbeth; Kwan, Tony; Medina-Gómez, Carolina; Pastinen, Tomi; Sigurdsson, Gunnar; Thorleifsson, Gudmar; vanMeurs, Joyce B.J.; Blangero, John; Hofman, Albert; Liu, Yongmei; Mitchell, Braxton D.; O’Connell, Jeffrey R.; Oostra, Ben A.; Rotter, Jerome I; Stefansson, Kari; Streeten, Elizabeth A.; Styrkarsdottir, Unnur; Thorsteinsdottir, Unnur; Tylavsky, Frances A.; Uitterlinden, Andre; Cauley, Jane A.; Harris, Tamara B.; Ioannidis, John P.A.; Psaty, Bruce M.; Robbins, John A; Zillikens, M. Carola; vanDuijn, Cornelia M.; Prince, Richard L.; Karasik, David; Rivadeneira, Fernando; Kiel, Douglas P.; Cupples, L. Adrienne; Hsu, Yi-Hsiang

2012-01-01

Background Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed eQTL analysis and bioinformatics network analysis. Methods We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS-) and femoral neck (FN-) BMD, in 25,353 individuals from eight cohorts. In a second stage, we followed up the 12 top SNPs (P<1×10−5) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. Results We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect = 0.02 & p-value = 3.0×10−5; female effect = −0.007 & p-value=3.3×10−2) and eleven suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (P<5×10−8) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Conclusion Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found influencing BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP. PMID:22692763

HGF/c-Met related activation of β-catenin in hepatoblastoma

PubMed Central

2011-01-01

Background Activation of beta-catenin is a hallmark of hepatoblastoma (HB) and appears to play a crucial role in its pathogenesis. While aberrant accumulation of the beta-catenin is a common event in HB, mutations or deletions in CTNNB1 (beta-catenin gene) do not always account for the high frequency of protein expression. In this study we have investigated alternative activation of beta-catenin by HGF/c-Met signaling in a large cohort of 98 HB patients enrolled in the SIOPEL-3 clinical trial. Methods We performed immunohistochemistry, using antibodies to total beta-catenin and tyrosine654-phosphorylated beta-catenin, which is a good surrogate marker of HGF/c-Met activation. CTNNB1 mutation analysis was also carried out on all samples. We also investigated beta-catenin pathway activation in two liver cancer cell lines, HuH-6 and HuH-7. Results Aberrant beta-catenin expression was seen in the cytoplasm and/or nucleus of 87% of tumour samples. Our results also revealed a large subset of HB, 83%, with cytoplasmic expression of tyrosine654-phosphorylated beta-catenin and 30% showing additional nuclear accumulation. Sequence analysis revealed mutations in 15% of our cohort. Statistical analysis showed an association between nuclear expression of c-Met-activated beta-catenin and wild type CTNNB1 (P-value = 0.015). Analysis of total beta-catenin and Y654-beta-catenin in response to HGF activation in the cell lines, mirrors that observed in our HB tumour cohort. Results We identified a significant subset of hepatoblastoma patients for whom targeting of the c-Met pathway may be a treatment option and also demonstrate distinct mechanisms of beta-catenin activation in HB. PMID:21992464

Developing and validating a predictive model for stroke progression.

PubMed

Craig, L E; Wu, O; Gilmour, H; Barber, M; Langhorne, P

2011-01-01

Progression is believed to be a common and important complication in acute stroke, and has been associated with increased mortality and morbidity. Reliable identification of predictors of early neurological deterioration could potentially benefit routine clinical care. The aim of this study was to identify predictors of early stroke progression using two independent patient cohorts. Two patient cohorts were used for this study - the first cohort formed the training data set, which included consecutive patients admitted to an urban teaching hospital between 2000 and 2002, and the second cohort formed the test data set, which included patients admitted to the same hospital between 2003 and 2004. A standard definition of stroke progression was used. The first cohort (n = 863) was used to develop the model. Variables that were statistically significant (p < 0.1) on univariate analysis were included in the multivariate model. Logistic regression was the technique employed using backward stepwise regression to drop the least significant variables (p > 0.1) in turn. The second cohort (n = 216) was used to test the performance of the model. The performance of the predictive model was assessed in terms of both calibration and discrimination. Multiple imputation methods were used for dealing with the missing values. Variables shown to be significant predictors of stroke progression were conscious level, history of coronary heart disease, presence of hyperosmolarity, CT lesion, living alone on admission, Oxfordshire Community Stroke Project classification, presence of pyrexia and smoking status. The model appears to have reasonable discriminative properties [the median receiver-operating characteristic curve value was 0.72 (range 0.72-0.73)] and to fit well with the observed data, which is indicated by the high goodness-of-fit p value [the median p value from the Hosmer-Lemeshow test was 0.90 (range 0.50-0.92)]. The predictive model developed in this study contains variables that can be easily collected in practice therefore increasing its usability in clinical practice. Using this analysis approach, the discrimination and calibration of the predictive model appear sufficiently high to provide accurate predictions. This study also offers some discussion around the validation of predictive models for wider use in clinical practice.

Parental Separation and Cardiometabolic Risk Factors in Late Adolescence: A Cross-Cohort Comparison.

PubMed

Soares, Ana Luiza Gonçalves; Gonçalves, Helen; Matijasevich, Alicia; Sequeira, Maija; Smith, George Davey; Menezes, Ana M B; Assunção, Maria Cecília; Wehrmeister, Fernando C; Fraser, Abigail; Howe, Laura D

2017-05-15

The aim of this study was to explore the association between parental separation during childhood (up to 18 years of age) and cardiometabolic risk factors (body mass index, fat mass index, blood pressure, physical activity, smoking, and alcohol consumption) in late adolescence using a cross-cohort comparison and to explore whether associations differ according to the age at which the parental separation occurred and the presence or absence of parental conflict prior to separation. Data from the Avon Longitudinal Study of Parents and Children (ALSPAC, United Kingdom) (1991-2011) and the 1993 Pelotas Birth Cohort (Brazil) (1993-2011) were used. The associations of parental separation with children's cardiometabolic risk factors were largely null. Higher odds of daily smoking were observed in both cohorts for those adolescents whose parents separated (for ALSPAC, odds ratio = 1.46; for Pelotas Birth Cohort, odds ratio = 1.98). Some additional associations were observed in the Pelotas Birth Cohort but were generally in the opposite direction to our a priori hypothesis: Parental separation was associated with lower blood pressure and fat mass index, and with more physical activity. No consistent differences were observed when analyses were stratified by child's age at parental separation or parental conflict. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

Vimentin and Ki67 expression in circulating tumour cells derived from castrate-resistant prostate cancer.

PubMed

Lindsay, C R; Le Moulec, S; Billiot, F; Loriot, Y; Ngo-Camus, M; Vielh, P; Fizazi, K; Massard, C; Farace, F

2016-02-29

High circulating tumor cell (CTC) counts are associated with poor prognosis in advanced prostate cancer, and recently CTC number was suggested to be a surrogate for survival in metastatic castrate-resistant prostate cancer (mCRPC). Ki67 and vimentin are well-characterised markers of tumour cell proliferation and the epithelial-mesenchymal transition (EMT), respectively. Here we asked if the expression of vimentin and Ki67 in CTCs offered prognostic or predictive information in mCRPC. In two separate patient cohorts, anti-vimentin or anti-Ki67 antibodies were added to the free channel in the CellSearch® system for analysis of peripheral blood samples. For each cohort, association of CTC number with clinical characteristics were assessed using Fisher's exact, Mann-Whitney and chi-squared tests. Kaplan-Meier method and log-rank tests were used to analyse overall survival (OS) of vimentin-expressing and Ki67-expressing CTC patient cohorts. In this retrospective analysis, CTC vimentin expression was analysed in 142 blood samples from 93 patients, and CTC Ki67 expression was analysed in 90 blood samples from 51 patients. In the vimentin cohort, 80/93 (86 %) of baseline samples from patients were CTC-positive overall (≥1 total CTC per 7.5 mls blood), and 30/93 (32.3 %) vimentin CTC-positive (≥1 vimentin-positive CTC per 7.5 mls blood). 41/51 (80.4 %) of baseline samples from patients in the Ki67 cohort were CTC-positive overall, and 23/51 (45.1 %) Ki67 CTC-positive (≥1 Ki67-positive CTC per 7.5 mls blood). There was no significant difference in baseline PSA in patients with vimentin-positive CTC at baseline versus those with no vimentin-positive CTC at baseline (p = 0.33). A significant reduction in OS was shown in patients with vimentin-positive CTC compared to those without vimentin-positive CTC (median 305 days vs 453 days, p = 0.0293). There was no significant difference in baseline PSA in patients with Ki67-positive CTC at baseline versus those without Ki67-positive CTC (p = 0.228), but OS was significantly reduced in the Ki67-positive CTC group (median 512 days vs 751 days, p = 0.0091). No changes in relative proportion of vimentin- or Ki67-positive CTCs were observed in post-treatment samples compared to baseline. Analysis of vimentin and Ki67 expression can straightforwardly be assessed in CTCs from patients with mCRPC. Poorer survival outcomes were observed in vimentin- and Ki67-positive CTC patients. CEC-CTC (IDRCB2008-AOO585-50) and Petrus ( NCT01786031 ).

Chronic urinary tract infection and bladder carcinoma risk: a meta-analysis of case-control and cohort studies.

PubMed

Akhtar, Saeed; Al-Shammari, Ahmad; Al-Abkal, Jarrah

2018-02-05

This meta-analysis of published case-control and cohort studies sought to quantify the magnitude and direction of association between chronic UTI (defined as the infection of the urinary tract that either does not respond to treatment or keeps recurring) and risk of bladder carcinoma (BCa) (i.e., including mainly urothelial carcinoma, squamous cell carcinoma or adenocarcinoma). A literature search was conducted using Medline, Embase, Ovid, Web of Science, Science Direct and Cochrane Library, which was supplemented with manual search of reference lists of the identified articles. Case-control and cohort studies examining UTI as a predictor of BCa risk published through June 2016 were eligible. Using random-effects models, odds ratios (OR) or relative risks (RR) from eligible studies were combined to synthesize summary effect estimates. The included studies were assessed for methodological quality and potential publication bias. Heterogeneity by study characteristics was examined by sub-group and meta-regression analyses. Eighteen case-control and three cohort studies published between 1963 and 2016 were eligible. Random-effects models showed that UTI was significantly associated with an increased BCa risk both in case-control studies (summary OR RE  = 2.33; 95% CI 1.86, 2.92) and cohort studies (summary RR RE  = 2.88; 95% CI 1.20, 6.89). The observed relationship of UTI with an increased BCa risk was independent of the study characteristics considered. No significant publication bias was detected. Chronic UTI was significantly and independently associated with an increased BCa risk. However, due to the presence of high between-study heterogeneity and inconsistent patterns of adjusted confounding effects, more data are needed to clarify the role of chronic UTI in causation of BCa and if established, prompt and effective treatment of UTI may minimize a substantial proportion of BCa risk.

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.

Body mass index and risk of BPH: a meta-analysis.

PubMed

Wang, S; Mao, Q; Lin, Y; Wu, J; Wang, X; Zheng, X; Xie, L

2012-09-01

Epidemiological studies have reported conflicting results relating obesity to BPH. A meta-analysis of cohort and case-control studies was conducted to pool the risk estimates of the association between obesity and BPH. Eligible studies were retrieved by both computer searches and review of references. We analyzed abstracted data with random effects models to obtain the summary risk estimates. Dose-response meta-analysis was performed for studies reporting categorical risk estimates for a series of exposure levels. A total of 19 studies met the inclusion criteria of the meta-analysis. Positive association with body mass index (BMI) was observed in BPH and lower urinary tract symptoms (LUTS) combined group (odds ratio=1.27, 95% confidence intervals 1.05-1.53). In subgroup analysis, BMI exhibited a positive dose-response relationship with BPH/LUTS in population-based case-control studies and a marginal positive association was observed between risk of BPH and increased BMI. However, no association between BPH/LUTS and BMI was observed in other subgroups stratified by study design, geographical region or primary outcome. The overall current literatures suggested that BMI was associated with increased risk of BPH. Further efforts should be made to confirm these findings and clarify the underlying biological mechanisms.

Conversion of National Health Insurance Service-National Sample Cohort (NHIS-NSC) Database into Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM).

PubMed

You, Seng Chan; Lee, Seongwon; Cho, Soo-Yeon; Park, Hojun; Jung, Sungjae; Cho, Jaehyeong; Yoon, Dukyong; Park, Rae Woong

2017-01-01

It is increasingly necessary to generate medical evidence applicable to Asian people compared to those in Western countries. Observational Health Data Sciences a Informatics (OHDSI) is an international collaborative which aims to facilitate generating high-quality evidence via creating and applying open-source data analytic solutions to a large network of health databases across countries. We aimed to incorporate Korean nationwide cohort data into the OHDSI network by converting the national sample cohort into Observational Medical Outcomes Partnership-Common Data Model (OMOP-CDM). The data of 1.13 million subjects was converted to OMOP-CDM, resulting in average 99.1% conversion rate. The ACHILLES, open-source OMOP-CDM-based data profiling tool, was conducted on the converted database to visualize data-driven characterization and access the quality of data. The OMOP-CDM version of National Health Insurance Service-National Sample Cohort (NHIS-NSC) can be a valuable tool for multiple aspects of medical research by incorporation into the OHDSI research network.

Retrospective cohort study of a microelectronics and business machine facility.

PubMed

Silver, Sharon R; Pinkerton, Lynne E; Fleming, Donald A; Jones, James H; Allee, Steven; Luo, Lian; Bertke, Stephen J

2014-04-01

We examined health outcomes among 34,494 workers employed at a microelectronics and business machine facility 1969-2001. Standardized mortality ratio (SMR) and standardized incidence ratios were used to evaluate health outcomes in the cohort and Cox regression modeling to evaluate relations between scores for occupational exposures and outcomes of a priori interest. Just over 17% of the cohort (5,966 people) had died through 2009. All cause, all cancer, and many cause-specific SMRs showed statistically significant deficits. In hourly males, SMRs were significantly elevated for non-Hodgkin's lymphoma and rectal cancer. Salaried males had excess testicular cancer incidence. Pleural cancer and mesothelioma excesses were observed in workers hired before 1969, but no available records substantiate use of asbestos in manufacturing processes. A positive, statistically significant relation was observed between exposure scores for tetrachloroethylene and nervous system diseases. Few significant exposure-outcome relations were observed, but risks from occupational exposures cannot be ruled out due to data limitations and the relative youth of the cohort. © 2013 Wiley Periodicals, Inc.

Abacavir and cardiovascular disease: A critical look at the data.

PubMed

Llibre, Josep M; Hill, Andrew

2016-08-01

Most HIV-infected subjects will receive a treatment regimen including abacavir or tenofovir. Therefore, clarifying if there is an increased risk of acute myocardial infarction (AMI) among those exposed to abacavir is of the utmost importance. Due to the low frequency of AMI in this young population (2-5 per 1000 patients/year), efforts to clarify this have been quite controversial. While some observational cohorts have found a statistically significant association, others have not. Meta-analysis of randomized clinical trials offering the highest scientific evidence found no association at all, but with a limited statistical power to definitely rule out a small effect. A channelling or selection bias has been demonstrated in cohort studies, favouring the prescription of abacavir to subjects with or at risk for chronic kidney disease, and therefore, with an intrinsic increased cardiovascular risk. The recent NA-ACCORD cohort study does not identify an increased risk for AMI associated with recent abacavir use in a fully adjusted model (HR 1.33; 95%CI:0.96, 1.88). However, it does find an association in a second analysis restricted to treatment-naïve persons, with higher differences in baseline characteristics among compared arms. A critical review of the compiled available evidence is therefore mandatory, particularly in light of the first single-tablet regimen to receive approval that does contain abacavir. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical and demographic covariates of chronic opioid and non-opioid analgesic use in rural-dwelling older adults: the MoVIES project.

PubMed

Karp, Jordan F; Lee, Ching-Wen; McGovern, Jonathan; Stoehr, Gary; Chang, Chung-Chou H; Ganguli, Mary

2013-11-01

To describe covariates and patterns of late-life analgesic use in the rural, population-based MoVIES cohort from 1989 to 2002. Secondary analysis of epidemiologic survey of elderly people conducted over six biennial assessment waves. Potential covariates of analgesic use included age, gender, depression, sleep, arthritis, smoking, alcohol, and general health status. Of the original cohort of 1,681, this sample comprised 1,109 individuals with complete data on all assessments. Using trajectory analysis, participants were characterized as chronic or non-chronic users of opioid and non-opioid analgesics. Multivariable regression was used to model predictors of chronic analgesic use. The cohort was followed for mean (SD) 7.3 (2.7) years. Chronic use of opioid analgesics was reported by 7.2%, while non-opioid use was reported by 46.1%. In the multivariable model, predictors of chronic use of both opioid and non-opioid analgesics included female sex, taking ≥2 prescription medications, and "arthritis" diagnoses. Chronic opioid use was also associated with age 75-84 years; chronic non-opioid use was also associated with sleep continuity disturbance. These epidemiological data confirm clinical observations and generate hypotheses for further testing. Future studies should investigate whether addressing sleep problems might lead to decreased use of non-opioid analgesics and possibly enhanced pain management.

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

Consumption of garlic and risk of colorectal cancer: An updated meta-analysis of prospective studies

PubMed Central

Hu, Ji-Yi; Hu, Yi-Wang; Zhou, Jiao-Jiao; Zhang, Meng-Wen; Li, Dan; Zheng, Shu

2014-01-01

AIM: To conduct an updated meta-analysis of prospective studies addressing the association between garlic consumption and colorectal cancer. METHODS: Eligible cohort studies were identified by searching MEDLINE (PubMed) and screening the references of related articles published up to October 2013. Meta-analyses were conducted for colorectal cancer in relation to consumption of raw and cooked (RC) garlic and garlic supplements, separately. The summary relative risks (RR) with 95%CI were calculated using fixed-effects or random-effects model depending on the heterogeneity among studies. RESULTS: A total of 5 prospective cohort studies were identified. In contrast to the previous meta-analysis, no significant associations were found between consumption of RC garlic (RR: 1.06; 95%CI: 0.95-1.19) or garlic supplements (RR: 1.12; 95%CI: 0.96-1.31) and risk of colorectal cancer. A non-significant protective effect of garlic supplement intake against colorectal cancer was observed in females (RR: 0.84; 95%CI: 0.64-1.11), but the opposite was the case in males (RR: 1.24; 95%CI: 0.96-1.59). CONCLUSION: Consumption of RC garlic or garlic supplements is not significantly associated with reduced colorectal cancer risk. PMID:25386091

Consumption of garlic and risk of colorectal cancer: an updated meta-analysis of prospective studies.

PubMed

Hu, Ji-Yi; Hu, Yi-Wang; Zhou, Jiao-Jiao; Zhang, Meng-Wen; Li, Dan; Zheng, Shu

2014-11-07

To conduct an updated meta-analysis of prospective studies addressing the association between garlic consumption and colorectal cancer. Eligible cohort studies were identified by searching MEDLINE (PubMed) and screening the references of related articles published up to October 2013. Meta-analyses were conducted for colorectal cancer in relation to consumption of raw and cooked (RC) garlic and garlic supplements, separately. The summary relative risks (RR) with 95%CI were calculated using fixed-effects or random-effects model depending on the heterogeneity among studies. A total of 5 prospective cohort studies were identified. In contrast to the previous meta-analysis, no significant associations were found between consumption of RC garlic (RR: 1.06; 95%CI: 0.95-1.19) or garlic supplements (RR: 1.12; 95%CI: 0.96-1.31) and risk of colorectal cancer. A non-significant protective effect of garlic supplement intake against colorectal cancer was observed in females (RR: 0.84; 95%CI: 0.64-1.11), but the opposite was the case in males (RR: 1.24; 95%CI: 0.96-1.59). Consumption of RC garlic or garlic supplements is not significantly associated with reduced colorectal cancer risk.

Multiscale Analysis of Independent Alzheimer's Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus.

PubMed

Readhead, Ben; Haure-Mirande, Jean-Vianney; Funk, Cory C; Richards, Matthew A; Shannon, Paul; Haroutunian, Vahram; Sano, Mary; Liang, Winnie S; Beckmann, Noam D; Price, Nathan D; Reiman, Eric M; Schadt, Eric E; Ehrlich, Michelle E; Gandy, Sam; Dudley, Joel T

2018-06-21

Investigators have long suspected that pathogenic microbes might contribute to the onset and progression of Alzheimer's disease (AD) although definitive evidence has not been presented. Whether such findings represent a causal contribution, or reflect opportunistic passengers of neurodegeneration, is also difficult to resolve. We constructed multiscale networks of the late-onset AD-associated virome, integrating genomic, transcriptomic, proteomic, and histopathological data across four brain regions from human post-mortem tissue. We observed increased human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) from subjects with AD compared with controls. These results were replicated in two additional, independent and geographically dispersed cohorts. We observed regulatory relationships linking viral abundance and modulators of APP metabolism, including induction of APBB2, APPBP2, BIN1, BACE1, CLU, PICALM, and PSEN1 by HHV-6A. This study elucidates networks linking molecular, clinical, and neuropathological features with viral activity and is consistent with viral activity constituting a general feature of AD. Copyright © 2018 Elsevier Inc. All rights reserved.

Expression of PAM50 Genes in Lung Cancer: Evidence that Interactions between Hormone Receptors and HER2/HER3 Contribute to Poor Outcome.

PubMed

Siegfried, Jill M; Lin, Yan; Diergaarde, Brenda; Lin, Hui-Min; Dacic, Sanja; Pennathur, Arjun; Weissfeld, Joel L; Romkes, Marjorie; Nukui, Tomoko; Stabile, Laura P

2015-11-01

Non-small cell lung cancers (NSCLCs) frequently express estrogen receptor (ER) β, and estrogen signaling is active in many lung tumors. We investigated the ability of genes contained in the prediction analysis of microarray 50 (PAM50) breast cancer risk predictor gene signature to provide prognostic information in NSCLC. Supervised principal component analysis of mRNA expression data was used to evaluate the ability of the PAM50 panel to provide prognostic information in a stage I NSCLC cohort, in an all-stage NSCLC cohort, and in The Cancer Genome Atlas data. Immunohistochemistry was used to determine status of ERβ and other proteins in lung tumor tissue. Associations with prognosis were observed in the stage I cohort. Cross-validation identified seven genes that, when analyzed together, consistently showed survival associations. In pathway analysis, the seven-gene panel described one network containing the ER and progesterone receptor, as well as human epidermal growth factor receptor (HER)2/HER3 and neuregulin-1. NSCLC cases also showed a significant association between ERβ and HER2 protein expression. Cases positive for HER2 expression were more likely to express HER3, and ERβ-positive cases were less likely to be both HER2 and HER3 negative. Prognostic ability of genes in the PAM50 panel was verified in an ERβ-positive cohort representing all NSCLC stages. In The Cancer Genome Atlas data sets, the PAM50 gene set was prognostic in both adenocarcinoma and squamous cell carcinoma, whereas the seven-gene panel was prognostic only in squamous cell carcinoma. Genes in the PAM50 panel, including those linking ER and HER2, identify lung cancer patients at risk for poor outcome, especially among ERβ-positive cases and squamous cell carcinoma. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Multidimensional severity assessment in bronchiectasis: an analysis of seven European cohorts.

PubMed

McDonnell, M J; Aliberti, S; Goeminne, P C; Dimakou, K; Zucchetti, S C; Davidson, J; Ward, C; Laffey, J G; Finch, S; Pesci, A; Dupont, L J; Fardon, T C; Skrbic, D; Obradovic, D; Cowman, S; Loebinger, M R; Rutherford, R M; De Soyza, A; Chalmers, J D

2016-12-01

Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality. We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies. The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in 'severe' patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline. The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Genome Wide Meta-analysis Highlights the Role of Genetic Variation in RARRES2 in the Regulation of Circulating Serum Chemerin

PubMed Central

Breitfeld, Jana; Marzi, Carola; Grallert, Harald; Gross, Arnd; Ladenvall, Claes; Schleinitz, Dorit; Krause, Kerstin; Kirsten, Holger; Laurila, Esa; Kriebel, Jennifer; Thorand, Barbara; Rathmann, Wolfgang; Groop, Leif; Prokopenko, Inga; Isomaa, Bo; Beutner, Frank; Kratzsch, Jürgen; Thiery, Joachim; Fasshauer, Mathias; Klöting, Nora; Gieger, Christian; Blüher, Matthias; Stumvoll, Michael; Kovacs, Peter

2014-01-01

Chemerin is an adipokine proposed to link obesity and chronic inflammation of adipose tissue. Genetic factors determining chemerin release from adipose tissue are yet unknown. We conducted a meta-analysis of genome-wide association studies (GWAS) for serum chemerin in three independent cohorts from Europe: Sorbs and KORA from Germany and PPP-Botnia from Finland (total N = 2,791). In addition, we measured mRNA expression of genes within the associated loci in peripheral mononuclear cells by micro-arrays, and within adipose tissue by quantitative RT-PCR and performed mRNA expression quantitative trait and expression-chemerin association studies to functionally substantiate our loci. Heritability estimate of circulating chemerin levels was 16.2% in the Sorbs cohort. Thirty single nucleotide polymorphisms (SNPs) at chromosome 7 within the retinoic acid receptor responder 2 (RARRES2)/Leucine Rich Repeat Containing (LRRC61) locus reached genome-wide significance (p<5.0×10−8) in the meta-analysis (the strongest evidence for association at rs7806429 with p = 7.8×10−14, beta = −0.067, explained variance 2.0%). All other SNPs within the cluster were in linkage disequilibrium with rs7806429 (minimum r2 = 0.43 in the Sorbs cohort). The results of the subgroup analyses of males and females were consistent with the results found in the total cohort. No significant SNP-sex interaction was observed. rs7806429 was associated with mRNA expression of RARRES2 in visceral adipose tissue in women (p<0.05 after adjusting for age and body mass index). In conclusion, the present meta-GWAS combined with mRNA expression studies highlights the role of genetic variation in the RARRES2 locus in the regulation of circulating chemerin concentrations. PMID:25521368

A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk.

PubMed

Alexander, Dominik D; Miller, Paige E; Van Elswyk, Mary E; Kuratko, Connye N; Bylsma, Lauren C

2017-01-01

To conduct meta-analyses of randomized controlled trials (RCTs) to estimate the effect of eicosapentaenoic and docosahexaenoic acid (EPA+DHA) on coronary heart disease (CHD), and to conduct meta-analyses of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk. A systematic literature search of Ovid/Medline, PubMed, Embase, and the Cochrane Library from January 1, 1947, to November 2, 2015, was conducted; 18 RCTs and 16 prospective cohort studies examining EPA+DHA from foods or supplements and CHD, including myocardial infarction, sudden cardiac death, coronary death, and angina, were identified. Random-effects meta-analysis models were used to generate summary relative risk estimates (SRREs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses and by meta-regression. Dose-response was evaluated in stratified dose or intake analyses. Publication bias assessments were performed. Among RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event. Results indicate that EPA+DHA may be associated with reducing CHD risk, with a greater benefit observed among higher-risk populations in RCTs. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Olive oil in the prevention and management of type 2 diabetes mellitus: a systematic review and meta-analysis of cohort studies and intervention trials

PubMed Central

Schwingshackl, L; Lampousi, A-M; Portillo, M P; Romaguera, D; Hoffmann, G; Boeing, H

2017-01-01

Background/Objectives: Olive oil (OO) as food is composed mainly of fatty acids and bioactive compounds depending from the extraction method. Both had been discussed as health promoting with still open questions. Thus, we conducted a meta-analysis to illustrate the impact of this food on type 2 diabetes (T2D) by investigating the association between OO intake and risk of T2D, and the effect of OO intake in the management of T2D. Subjects/Methods: Searches were performed in PubMed, Cochrane Library and google scholar. First, we conducted a random effect meta-analysis of prospective cohort studies and trials investigating the association between OO and risk of T2D. Second, a meta-analysis was performed to detect the effects of olive oil on glycemic control in patients with T2D. Results: Four cohort studies including 15 784 T2D cases and 29 trials were included in the meta-analysis. The highest OO intake category showed a 16% reduced risk of T2D (RR: 0.84; 95% CI: 0.77, 0.92) compared with the lowest. However, we observed evidence for a nonlinear relationship. In T2D patients OO supplementation resulted in a significantly more pronounced reduction in HbA1c (MD: −0.27% 95% CI: −0.37, −0.17) and fasting plasma glucose (MD: −0.44 mmol l−1; 95% CI −0.66, −0.22) as compared with the control groups. Conclusions: This meta-analysis provides evidence that the intake of OO could be beneficial for the prevention and management of T2D. This conclusion regards OO as food, and might not been valid for single components comprising this food. PMID:28394365

Changes in body mass index in children with juvenile idiopathic arthritis treated with tumor necrosis factor inhibitors.

PubMed

Shafferman, Ashley; Fontaine, Kevin R; Cron, Randy Q; Beukelman, Timothy

2014-01-01

To evaluate changes in body mass index (BMI) among cohorts of children with juvenile idiopathic arthritis (JIA) with and without tumor necrosis factor (TNF) inhibitor therapy. We performed a retrospective chart review of children with JIA who newly initiated TNF inhibitor therapy and had at least 1 year of subsequent followup (TNF cohort). We also included children with JIA and at least 1 year of followup without any TNF inhibitor therapy (comparator cohort). Children with systemic arthritis were excluded. Age and sex specific BMI z-scores and their corresponding categories (normal, overweight, obese) were determined. We compared changes from a baseline visit to the last followup visit using t-test for BMI z-scores and chi square and Kruskal-Wallis tests for BMI categories. The TNF cohort had 167 patients; the comparator cohort had 37. The median study followup was 2.8 and 2.2 years, respectively. The cohorts had similar age, sex, race, weight, and height distributions. The TNF cohort had a statistically significant increase in BMI z-score from baseline (+0.15; p = 0.02) that was not significantly different from the increase (+0.09) observed in the comparator cohort (p = 0.5). There was no significant change in the proportions of overweight and obese children in the TNF cohort compared to baseline (p = 0.6) or compared to the change in the comparator cohort (p = 0.2). Over more than 2 years of followup, we did not observe a significant increase in BMI among children with JIA receiving TNF inhibitor compared to those not receiving it.

Dietary fiber intake and total mortality: a meta-analysis of prospective cohort studies.

PubMed

Kim, Youngyo; Je, Youjin

2014-09-15

Greater intake of dietary fiber has been associated with lower risk of several chronic diseases. Some observational studies have examined the association between dietary fiber intake and total mortality, but the results were inconclusive. We conducted a meta-analysis of data from prospective cohort studies to quantitatively assess the association. Eligible studies were identified by searching the PubMed and Embase databases for all articles published through November 30, 2013, and by reviewing the reference lists of retrieved articles. Study-specific estimates adjusting for potential confounders were combined to calculate a pooled relative risk and 95% confidence interval using a random-effects model. Seven prospective cohort studies of dietary fiber intake and total mortality, including 62,314 deaths among 908,135 participants, were identified. The pooled adjusted relative risk of total mortality for the highest category of dietary fiber intake versus the lowest was 0.77 (95% confidence interval: 0.74, 0.80). In a dose-response meta-analysis, the pooled adjusted relative risk for a 10-g/day increment of dietary fiber intake was 0.89 (95% confidence interval: 0.85, 0 92). By source of fiber, cereal and, to a lesser extent, vegetable fiber were significantly associated with lower total mortality, while fruit fiber showed no association. In conclusion, high dietary fiber intake may reduce the risk of total mortality. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Observational Studies: Cohort and Case-Control Studies

PubMed Central

Song, Jae W.; Chung, Kevin C.

2010-01-01

Observational studies are an important category of study designs. To address some investigative questions in plastic surgery, randomized controlled trials are not always indicated or ethical to conduct. Instead, observational studies may be the next best method to address these types of questions. Well-designed observational studies have been shown to provide results similar to randomized controlled trials, challenging the belief that observational studies are second-rate. Cohort studies and case-control studies are two primary types of observational studies that aid in evaluating associations between diseases and exposures. In this review article, we describe these study designs, methodological issues, and provide examples from the plastic surgery literature. PMID:20697313

Does vagotomy protect against multiple sclerosis?

PubMed

Sundbøll, Jens; Horváth-Puhó, Erzsébet; Adelborg, Kasper; Svensson, Elisabeth

2017-07-01

To examine the association between vagotomy and multiple sclerosis. We conducted a matched cohort study of all patients who underwent truncal or super-selective vagotomy and a comparison cohort, by linking Danish population-based medical registries (1977-1995). Hazard ratios (HRs) for multiple sclerosis, adjusting for potential confounders were computed by means of Cox regression analysis. Median age of multiple sclerosis onset corresponded to late onset multiple sclerosis. No association with multiple sclerosis was observed for truncal vagotomy (0-37 year adjusted HR=0.91, 95% confidence interval [CI]: 0.48-1.74) or super-selective vagotomy (0-37 year adjusted HR=1.28, 95% CI: 0.79-2.09) compared with the general population. We found no association between vagotomy and later risk of late onset multiple sclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

New treatments compared to established treatments in randomized trials

PubMed Central

Djulbegovic, Benjamin; Kumar, Ambuj; Glasziou, Paul P; Perera, Rafael; Reljic, Tea; Dent, Louise; Raftery, James; Johansen, Marit; Di Tanna, Gian Luca; Miladinovic, Branko; Soares, Heloisa P; Vist, Gunn E; Chalmers, Iain

2012-01-01

Background The proportion of proposed new treatments that are ’successful’ is of ethical, scientific, and public importance. We investigated how often new, experimental treatments evaluated in randomized controlled trials (RCTs) are superior to established treatments. Objectives Our main question was: “On average how often are new treatments more effective, equally effective or less effective than established treatments?” Additionally, we wanted to explain the observed results, i.e. whether the observed distribution of outcomes is consistent with the ’uncertainty requirement’ for enrollment in RCTs. We also investigated the effect of choice of comparator (active versus no treatment/placebo) on the observed results. Search methods We searched the Cochrane Methodology Register (CMR) 2010, Issue 1 in The Cochrane Library (searched 31 March 2010); MEDLINE Ovid 1950 to March Week 2 2010 (searched 24 March 2010); and EMBASE Ovid 1980 to 2010 Week 11 (searched 24 March 2010). Selection criteria Cohorts of studies were eligible for the analysis if they met all of the following criteria: (i) consecutive series of RCTs, (ii) registered at or before study onset, and (iii) compared new against established treatments in humans. Data collection and analysis RCTs from four cohorts of RCTs met all inclusion criteria and provided data from 743 RCTs involving 297,744 patients. All four cohorts consisted of publicly funded trials. Two cohorts involved evaluations of new treatments in cancer, one in neurological disorders, and one for mixed types of diseases. We employed kernel density estimation, meta-analysis and meta-regression to assess the probability of new treatments being superior to established treatments in their effect on primary outcomes and overall survival. Main results The distribution of effects seen was generally symmetrical in the size of difference between new versus established treatments. Meta-analytic pooling indicated that, on average, new treatments were slightly more favorable both in terms of their effect on reducing the primary outcomes (hazard ratio (HR)/odds ratio (OR) 0.91, 99% confidence interval (CI) 0.88 to 0.95) and improving overall survival (HR 0.95, 99% CI 0.92 to 0.98). No heterogeneity was observed in the analysis based on primary outcomes or overall survival (I2 = 0%). Kernel density analysis was consistent with the meta-analysis, but showed a fairly symmetrical distribution of new versus established treatments indicating unpredictability in the results. This was consistent with the interpretation that new treatments are only slightly superior to established treatments when tested in RCTs. Additionally, meta-regression demonstrated that results have remained stable over time and that the success rate of new treatments has not changed over the last half century of clinical trials. The results were not significantly affected by the choice of comparator (active versus placebo/no therapy). Authors’ conclusions Society can expect that slightly more than half of new experimental treatments will prove to be better than established treatments when tested in RCTs, but few will be substantially better. This is an important finding for patients (as they contemplate participation in RCTs), researchers (as they plan design of the new trials), and funders (as they assess the ’return on investment’). Although we provide the current best evidence on the question of expected ’success rate’ of new versus established treatments consistent with a priori theoretical predictions reflective of ’uncertainty or equipoise hypothesis’, it should be noted that our sample represents less than 1% of all available randomized trials; therefore, one should exercise the appropriate caution in interpretation of our findings. In addition, our conclusion applies to publicly funded trials only, as we did not include studies funded by commercial sponsors in our analysis. PMID:23076962

Asthma-Related Outcomes in Patients Initiating Extrafine Ciclesonide or Fine-Particle Inhaled Corticosteroids

PubMed Central

Postma, Dirkje S.; Dekhuijzen, Richard; van der Molen, Thys; Martin, Richard J.; van Aalderen, Wim; Roche, Nicolas; Guilbert, Theresa W.; Israel, Elliot; van Eickels, Daniela; Khalid, Javaria Mona; Herings, Ron M.C.; Overbeek, Jetty A.; Miglio, Cristiana; Thomas, Victoria; Hutton, Catherine; Hillyer, Elizabeth V.

2017-01-01

Purpose Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone). Methods This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as ciclesonide or fine-particle ICS. The 2 cohorts were matched 1:1 for key demographic and clinical characteristics over the baseline year. Co-primary endpoints were 1-year severe exacerbation rates, risk-domain asthma control, and overall asthma control; secondary endpoints included therapy change. Results Each cohort included 1,244 patients (median age 45 years; 65% women). Patients in the ciclesonide cohort were comparable to those in the fine-particle ICS cohort apart from higher baseline prevalence of hospitalization, gastroesophageal reflux disease, and rhinitis. Median (interquartile range) prescribed doses of ciclesonide and fine-particle ICS were 160 (160-160) µg/day and 500 (250-500) µg/day, respectively (P<0.001). During the outcome year, patients prescribed ciclesonide experienced lower severe exacerbation rates (adjusted rate ratio [95% CI], 0.69 [0.53-0.89]), and higher odds of risk-domain asthma control (adjusted odds ratio [95% CI], 1.62 [1.27-2.06]) and of overall asthma control (2.08 [1.68-2.57]) than those prescribed fine-particle ICS. The odds of therapy change were 0.70 (0.59-0.83) with ciclesonide. Conclusions In this matched cohort analysis, we observed that initiation of ICS with ciclesonide was associated with better 1-year asthma outcomes and fewer changes to therapy, despite data suggesting more difficult-to-control asthma. The median prescribed dose of ciclesonide was one-third that of fine-particle ICS. PMID:28102056

Gastric Bypass Surgery Produces a Durable Reduction in Cardiovascular Disease Risk Factors and Reduces the Long-Term Risks of Congestive Heart Failure.

PubMed

Benotti, Peter N; Wood, G Craig; Carey, David J; Mehra, Vishal C; Mirshahi, Tooraj; Lent, Michelle R; Petrick, Anthony T; Still, Christopher; Gerhard, Glenn S; Hirsch, Annemarie G

2017-05-23

Obesity and its association with reduced life expectancy are well established, with cardiovascular disease as one of the major causes of fatality. Metabolic surgery is a powerful intervention for severe obesity, resulting in improvement in comorbid diseases and in cardiovascular risk factors. This study investigates the relationship between metabolic surgery and long-term cardiovascular events. A cohort of Roux-en-Y gastric bypass surgery (RYGB) patients was tightly matched by age, body mass index, sex, Framingham Risk Score, smoking history, use of antihypertension medication, diabetes mellitus status, and calendar year with a concurrent cohort of nonoperated control patients. The primary study end points of major cardiovascular events (myocardial infarction, stroke, and congestive heart failure) were evaluated using Cox regression. Secondary end points of longitudinal cardiovascular risk factors were evaluated using repeated-measures regression. The RYGB and matched controls (N=1724 in each cohort) were followed for up to 12 years after surgery (overall median of 6.3 years). Kaplan-Meier analysis revealed a statistically significant reduction in incident major composite cardiovascular events ( P =0.017) and congestive heart failure (0.0077) for the RYGB cohort. Adjusted Cox regression models confirmed the reductions in severe composite cardiovascular events in the RYGB cohort (hazard ratio=0.58, 95% CI=0.42-0.82). Improvements of cardiovascular risk factors (eg, 10-year cardiovascular risk score, total cholesterol, high-density lipoprotein, systolic blood pressure, and diabetes mellitus) were observed within the RYGB cohort after surgery. Gastric bypass is associated with a reduced risk of major cardiovascular events and the development of congestive heart failure. © 2017 The Authors and Geisinger Clinic. Published on behalf of the American Heart Association, Inc., by Wiley.

Development and validation of the Surgical Outcome Risk Tool (SORT)

PubMed Central

Protopapa, K L; Simpson, J C; Smith, N C E; Moonesinghe, S R

2014-01-01

Background Existing risk stratification tools have limitations and clinical experience suggests they are not used routinely. The aim of this study was to develop and validate a preoperative risk stratification tool to predict 30-day mortality after non-cardiac surgery in adults by analysis of data from the observational National Confidential Enquiry into Patient Outcome and Death (NCEPOD) Knowing the Risk study. Methods The data set was split into derivation and validation cohorts. Logistic regression was used to construct a model in the derivation cohort to create the Surgical Outcome Risk Tool (SORT), which was tested in the validation cohort. Results Prospective data for 19 097 cases in 326 hospitals were obtained from the NCEPOD study. Following exclusion of 2309, details of 16 788 patients were analysed (derivation cohort 11 219, validation cohort 5569). A model of 45 risk factors was refined on repeated regression analyses to develop a model comprising six variables: American Society of Anesthesiologists Physical Status (ASA-PS) grade, urgency of surgery (expedited, urgent, immediate), high-risk surgical specialty (gastrointestinal, thoracic, vascular), surgical severity (from minor to complex major), cancer and age 65 years or over. In the validation cohort, the SORT was well calibrated and demonstrated better discrimination than the ASA-PS and Surgical Risk Scale; areas under the receiver operating characteristic (ROC) curve were 0·91 (95 per cent c.i. 0·88 to 0·94), 0·87 (0·84 to 0·91) and 0·88 (0·84 to 0·92) respectively (P < 0·001). Conclusion The SORT allows rapid and simple data entry of six preoperative variables, and provides a percentage mortality risk for individuals undergoing surgery. PMID:25388883

[Mortality study in metal electroplating workers in Bologna (Northern Italy)].

PubMed

Gerosa, Alberto; Scarnato, Corrado; Giacomozzi, Giuseppe; d'Errico, Angelo

2013-01-01

to investigate general and cause-specific mortality of workers exposed to metals and other chemicals in the electroplating industry in Bologna Province. factory records of workers employed in 90 electroplating companies present in 1995 were used to build a cohort of subjects potentially exposed to carcinogenic and other substances in this industry, defined as "revised cohort", which was followed-up for mortality from 1960, or since first employment in an electroplating company if later, to 2008. Mortality risk was also examined separately in a subset of the cohort, composed of workers with at least one year of employment in electroplating, denominated "final cohort". Death rates of residents in Emilia-Romagna Region (Northern Italy) were used as a reference. follow-up completeness was 99%. During the observation period, 533 deaths out of 2,983 subjects were observed in the revised cohort and 317 out of 1,739 in the final cohort. Significantly increased Standardized Mortality Ratios were estimated for overall mortality and for mortality from AIDS in the revised cohort and for bladder and rectal cancer in both cohorts. the present study is, to authors' knowledge, the largest mortality investigation conducted in Italy on electroplating workers, for both size and temporal extension. The presence of excess mortality from causes of death not consistently associated in the literature with exposure to agents in this industry suggests that further research is needed to confirm these associations.

Cohort Profile: HAART Observational Medical Evaluation and Research (HOMER) Cohort

PubMed Central

Patterson, Sophie; Cescon, Angela; Samji, Hasina; Cui, Zishan; Yip, Benita; Lepik, Katherine J; Moore, David; Lima, Viviane D; Nosyk, Bohdan; Harrigan, P Richard; Montaner, Julio SG; Shannon, Kate; Wood, Evan; Hogg, Robert S

2015-01-01

Since 1986, antiretroviral therapy (ART) has been available free of charge to individuals living with HIV in British Columbia (BC), Canada, through the BC Centre of Excellence in HIV/AIDS (BC-CfE) Drug Treatment Program (DTP). The Highly Active Antiretroviral Therapy (HAART) Observational Medical Evaluation and Research (HOMER) cohort was established in 1996 to maintain a prospective record of clinical measurements and medication profiles of a subset of DTP participants initiating HAART in BC. This unique cohort provides a comprehensive data source to investigate mortality, prognostic factors and treatment response among people living with HIV in BC from the inception of HAART. Currently over 5000 individuals are enrolled in the HOMER cohort. Data captured include socio-demographic characteristics (e.g. sex, age, ethnicity, health authority), clinical variables (e.g. CD4 cell count, plasma HIV viral load, AIDS-defining illness, hepatitis C co-infection, mortality) and treatment variables (e.g. HAART regimens, date of treatment initiation, treatment interruptions, adherence data, resistance testing). Research findings from the HOMER cohort have featured in numerous high-impact peer-reviewed journals. The HOMER cohort collaborates with other HIV cohorts on both national and international scales to answer complex HIV-specific research questions, and welcomes input from external investigators regarding potential research proposals or future collaborations. For further information please contact the principal investigator, Dr Robert Hogg (robert_hogg@sfu.ca). PMID:24639444

Transmission routes maintaining a viral pathogen of steelhead trout within a complex multi-host assemblage

USGS Publications Warehouse

Breyta, Rachel; Brito, Ilana L.; Ferguson, Paige; Kurath, Gael; Naish, Kerry A.; Purcell, Maureen; Wargo, Andrew R.; LaDeau, Shannon L.

2017-01-01

This is the first comprehensive region wide, spatially explicit epidemiologic analysis of surveillance data of the aquatic viral pathogen infectious hematopoietic necrosis virus (IHNV) infecting native salmonid fish. The pathogen has been documented in the freshwater ecosystem of the Pacific Northwest of North America since the 1950s, and the current report describes the disease ecology of IHNV during 2000–2012. Prevalence of IHNV infection in monitored salmonid host cohorts ranged from 8% to 30%, with the highest levels observed in juvenile steelhead trout. The spatial distribution of all IHNV-infected cohorts was concentrated in two sub-regions of the study area, where historic burden of the viral disease has been high. During the study period, prevalence levels fluctuated with a temporal peak in 2002. Virologic and genetic surveillance data were analyzed for evidence of three separate but not mutually exclusive transmission routes hypothesized to be maintaining IHNV in the freshwater ecosystem. Transmission between year classes of juvenile fish at individual sites (route 1) was supported at varying levels of certainty in 10%–55% of candidate cases, transmission between neighboring juvenile cohorts (route 2) was supported in 31%–78% of candidate cases, and transmission from adult fish returning to the same site as an infected juvenile cohort was supported in 26%–74% of candidate cases. The results of this study indicate that multiple specific transmission routes are acting to maintain IHNV in juvenile fish, providing concrete evidence that can be used to improve resource management. Furthermore, these results demonstrate that more sophisticated analysis of available spatio-temporal and genetic data is likely to yield greater insight in future studies.

Prognosis of acute idiopathic neck pain is poor: a systematic review and meta-analysis.

PubMed

Hush, Julia M; Lin, C Christine; Michaleff, Zoe A; Verhagen, Arianne; Refshauge, Kathryn M

2011-05-01

To conduct a systematic review and meta-analysis on the prognosis of acute idiopathic neck pain and disability. EMBASE, CINAHL, Medline, AMED, PEDro, and CENTRAL were searched from inception to July 2009, limited to human studies. Reference lists of relevant systematic reviews were searched by hand. Search terms included: neck pain, prognosis, inception, cohort, longitudinal, observational, or prospective study and randomized controlled trial. Eligible studies were longitudinal cohort studies and randomized controlled trials with a no treatment or minimal treatment arm that recruited an inception cohort of acute idiopathic neck pain and reported pain or disability outcomes. Eligibility was determined by 2 authors independently. Seven of 20,085 references were included. Pain and disability data were extracted independently by 2 authors. Risk of bias was assessed independently by 2 authors. Statistical pooling showed a weighted mean pain score (0-100) of 64 (95% confidence interval [CI], 61-67) at onset and 35 (95% CI, 32-38) at 6.5 weeks. At 12 months, neck pain severity remained high at 42 (95% CI, 39-45). Disability reduced from a pooled weighted mean score (0-100) at onset of 30 (95% CI, 28-32) to 17 (95% CI, 15-19) by 6.5 weeks, without further improvement at 12 months. Studies varied in length of follow-up, design, and sample size. This review provides Level I evidence that the prognosis of acute idiopathic neck pain is worse than currently recognized. This evidence can guide primary care clinicians when providing prognostic information to patients. Further research to identify prognostic factors and long-term outcomes from inception cohorts would be valuable. Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Ambulatory heart rate range predicts mode-specific mortality and hospitalisation in chronic heart failure

PubMed Central

Cubbon, Richard M; Ruff, Naomi; Groves, David; Eleuteri, Antonio; Denby, Christine; Kearney, Lorraine; Ali, Noman; Walker, Andrew M N; Jamil, Haqeel; Gierula, John; Gale, Chris P; Batin, Phillip D; Nolan, James; Shah, Ajay M; Fox, Keith A A; Sapsford, Robert J; Witte, Klaus K; Kearney, Mark T

2016-01-01

Objective We aimed to define the prognostic value of the heart rate range during a 24 h period in patients with chronic heart failure (CHF). Methods Prospective observational cohort study of 791 patients with CHF associated with left ventricular systolic dysfunction. Mode-specific mortality and hospitalisation were linked with ambulatory heart rate range (AHRR; calculated as maximum minus minimum heart rate using 24 h Holter monitor data, including paced and non-sinus complexes) in univariate and multivariate analyses. Findings were then corroborated in a validation cohort of 408 patients with CHF with preserved or reduced left ventricular ejection fraction. Results After a mean 4.1 years of follow-up, increasing AHRR was associated with reduced risk of all-cause, sudden, non-cardiovascular and progressive heart failure death in univariate analyses. After accounting for characteristics that differed between groups above and below median AHRR using multivariate analysis, AHRR remained strongly associated with all-cause mortality (HR 0.991/bpm increase in AHRR (95% CI 0.999 to 0.982); p=0.046). AHRR was not associated with the risk of any non-elective hospitalisation, but was associated with heart-failure-related hospitalisation. AHRR was modestly associated with the SD of normal-to-normal beats (R2=0.2; p<0.001) and with peak exercise-test heart rate (R2=0.33; p<0.001). Analysis of the validation cohort revealed AHRR to be associated with all-cause and mode-specific death as described in the derivation cohort. Conclusions AHRR is a novel and readily available prognosticator in patients with CHF, which may reflect autonomic tone and exercise capacity. PMID:26674986

Trends in breast, ovarian and cervical cancer incidence in Mumbai, India over a 30-year period, 1976–2005: an age–period–cohort analysis

PubMed Central

Dhillon, P K; Yeole, B B; Dikshit, R; Kurkure, A P; Bray, F

2011-01-01

Background: Demographic, socioeconomic and cultural changes in India have increased longevity, delayed childbearing, decreased parity and resulted in a more westernised lifestyle, contributing to the increasing burden of cancer, especially among women. Methods: We evaluated secular changes in the incidence of breast, cervical and ovarian cancer in Mumbai women aged 30–64 between 1976 and 2005. Age-standardised incidence rates were calculated and presented by site and calendar period. An age–period–cohort (APC) analysis quantified recent time trends and the significance of birth cohort and calendar period effects. The estimated annual percent change (EAPC) was obtained from the drift parameter, expressing the linear time trend common to both calendar period and birth cohort. Results: Over the 30-year study period, the age-standardised rates significantly increased for breast cancer (EAPC: 1.1% (95% confidence interval (CI): 1.0, 1.3)), significantly decreased for cervical cancer (EAPC: −1.8% (95% CI: −2.0, −1.6)) and there was no statistically significant change for ovarian cancer (EAPC: 0.3% (95% CI: −0.1, 0.6)). For breast and cervical cancer, the best-fitting model was the APC model. Conclusions: The rates of breast, cervical and ovarian cancer remain low in comparison with western countries, and the divergent trends of breast (increasing) and cervical cancer (decreasing) in Mumbai were similar to those observed in several other Asian countries. The changing risk profile in successive generations – improved education, higher socioeconomic status, later age at marriage and at first child, and lower parity – may in combination partially explain the diverging generational changes in breast and cervical cancer in Mumbai in the last decades. PMID:21829198

Fruit and vegetables consumption and incident hypertension: dose-response meta-analysis of prospective cohort studies.

PubMed

Wu, L; Sun, D; He, Y

2016-10-01

The role of dietary factors on chronic diseases seems essential in the potentially adverse or preventive effects. However, no evidence of dose-response meta-analysis of prospective cohort studies has verified the association between the intake of fruit and/or vegetables and the risk of developing hypertension. The PubMed and Embase were searched for prospective cohort studies. A generic inverse-variance method with random effects model was used to calculate the pooled relative risks (RRs) and 95% confidence intervals (CIs). Generalized least squares trend estimation model was used to calculate the study-specific slopes for the dose-response analyses. Seven articles comprised nine cohorts involving 185 676 participants were assessed. The highest intake of fruit or vegetables separately, and total fruit and vegetables were inversely associated with the incident risk of hypertension compared with the lowest level, and the pooled RRs and 95% CIs were 0.87 (0.79, 0.95), 0.88 (0.79, 0.99) and 0.90 (0.84, 0.98), respectively. We also found an inverse dose-response relation between the risk of developing hypertension and fruit intake, and total fruit and vegetables consumption. The incident risk of hypertension was decreased by 1.9% for each serving per day of fruit consumption, and decreased by 1.2% for each serving per day of total fruit and vegetables consumption. Our results support the recommendation to increase the consumption of fruit and vegetables with respect to preventing the risk of developing hypertension. However, further large prospective studies and long-term high-quality randomized controlled trials are still needed to confirm the observed association.

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.

Increase in overall mortality risk in patients with type 2 diabetes receiving glipizide, glyburide or glimepiride monotherapy versus metformin: a retrospective analysis.

PubMed

Pantalone, K M; Kattan, M W; Yu, C; Wells, B J; Arrigain, S; Jain, A; Atreja, A; Zimmerman, R S

2012-09-01

It remains uncertain if differences in mortality risk exist among the sulfonylureas, especially in patients with documented coronary artery disease (CAD). The purpose of this study was to assess the overall mortality risk of the individual sulfonylureas versus metformin in a large cohort of patients with type 2 diabetes. A retrospective cohort study was conducted using an academic health centre enterprise-wide electronic health record (EHR) system to identify 23 915 patients with type 2 diabetes who initiated monotherapy with metformin (N = 12774), glipizide (N = 4325), glyburide (N = 4279) or glimepiride (N = 2537), ≥ 18 years of age, with and without a history of CAD, and not on insulin or a non-insulin injectable at baseline. The patients were followed for mortality by documentation in the EHR and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare cohorts. An increase in overall mortality risk was observed in the entire cohort with glipizide (HR 1.64; 95% CI 1.39-1.94), glyburide (HR 1.59; 95% CI 1.35-1.88), and glimepiride (HR 1.68; 95% CI 1.37-2.06) versus metformin; however, in those patients with documented CAD, a statistically significant increase in overall mortality risk was only found with glipizide (HR 1.41; 95% CI 1.07-1.87) and glyburide (HR 1.38; 95% CI 1.04-1.83) versus metformin. Glipizide, glyburide and glimepiride are associated with an increased risk of overall mortality versus metformin. Our results suggest that if a sulfonylurea is required to obtain glycaemic control, glimepiride may be the preferred sulfonylurea in those with underlying CAD. © 2012 Blackwell Publishing Ltd.

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.

Non-steroidal anti-inflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review.

PubMed

Murphy, Megan A; Trabert, Britton; Yang, Hannah P; Park, Yikyung; Brinton, Louise A; Hartge, Patricia; Sherman, Mark E; Hollenbeck, Albert; Wentzensen, Nicolas

2012-11-01

Chronic inflammation has been proposed as a risk factor for ovarian cancer. Some data suggest that anti-inflammatory medications may be protective against ovarian cancer; however, results have been inconsistent. We evaluated the risk of epithelial ovarian cancer with regular use of NSAIDs prospectively in the NIH-AARP Diet and Health Study, using Cox proportional hazard models. We also examined the risk of common subtypes of epithelial ovarian cancer (serous, mucinous, endometrioid, clear cell, and other epithelial) with regular use of NSAIDs. In addition, we performed meta-analyses summarizing the risk of ovarian cancer with "regular use" of NSAIDs in previously published studies. We did not observe a significant association between regular use of NSAIDs with ovarian cancer risk in the AARP cohort (aspirin: RR 1.06, 95 % CI 0.87-1.29; non-aspirin NSAIDs: RR 0.93, 95 % CI 0.74-1.15); however, summary estimates from prospective cohort studies demonstrated that use of non-aspirin NSAIDs may reduce the risk of ovarian cancer (RR 0.88, 95 % CI 0.77-1.01). Although not significant, we found that mucinous tumors were inversely associated with non-aspirin NSAID use (RR 0.69, 95 % CI 0.23-2.10) in the AARP cohort, which was supported by the meta-analysis (RR 0.69, CI 0.50-0.94.) Although results from the NIH-AARP cohort study were not statistically significant, our meta-analysis suggests that non-aspirin NSAIDs may be protective against ovarian cancer. Additional analyses, focusing on dose, duration, and frequency of NSAID use and accounting for ovarian cancer heterogeneity are necessary to further elucidate the association between NSAID use and ovarian cancer risk.

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

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.

A risk-adapted protocol for delayed administration of filgrastim after high-dose chemotherapy and autologous stem cell transplantation.

PubMed

Khot, Amit; Dickinson, Michael; Stokes, Kerrie; Harrison, Simon; Burbury, Kate; Fleming, Shaun; Wall, Dominic; Gambell, Peter; Prince, H Miles; Seymour, John F; Ritchie, David

2013-02-01

The routine use of recombinant human granulocyte-colony stimulating factor (rhG-CSF) after high-dose chemotherapy and autologous stem cell transplantation (auto-SCT) is associated with increased costs. We prospectively explored a strategy that used prophylactic delayed filgrastim only in patients with risk factors. This sequential cohort analysis compared the outcomes of consecutive patients, treated on the risk-adapted protocol (RAP) (risk factors: prior febrile neutropenia; age >60 years; and CD34+ cell infused dose of <2 × 10(6/)/kg), who received filgrastim from day +6 after auto-SCT with a historical cohort (historical day-1 cohort [HD1]), who received filgrastim from day +1. Eighty-two patients were treated in the RAP cohort and compared with 115 patients in the HD1 cohort. There were no differences in median age (55 years) or median CD34+ cell dose (5.21 × 10(6)/kg [range, 2-62.2 × 10(6)/kg] vs. 5.24 × 10(6)/kg [range, 2.4-29.8 × 10(6)/kg]). Filgrastim was used for 6 fewer days in the RAP cohort (median 5 days [range, 0-11 days] vs. 11 days [range, 9-47 days]). There was a small absolute but significant difference in median time to neutrophil recovery in the HD1 cohort for the whole group, 10 days (range, 8-46 days) vs. 11 days (range, 9-22 days) (P = .03) and in patients with myeloma; 10 days (range, 9-14 days) vs. 11 days (range, 9-18 days) (P < .0001) as compared to the RAP cohort. There was no difference in median inpatient duration, 13 days (range, 10-26 days) vs. 12 days (range, 1-38 days) (P = .22) and 3-year survival (79% vs. 83% [P = .43]) between HD1 and RAP cohorts respectively. The use of a RAP to identify patients likely to benefit from prophylactic filgrastim is safe and results in cost savings. Patients with myeloma benefit from earlier introduction of filgrastim in terms of neutrophil recovery; this disease-specific observation is an important consideration for future studies. Copyright © 2013 Elsevier Inc. All rights reserved.

Clinical prediction models for young febrile infants at the emergency department: an international validation study.

PubMed

Vos-Kerkhof, Evelien de; Gomez, Borja; Milcent, Karen; Steyerberg, Ewout W; Nijman, Ruud Gerard; Smit, Frank J; Mintegi, Santiago; Moll, Henriette A; Gajdos, Vincent; Oostenbrink, Rianne

2018-05-24

To assess the diagnostic value of existing clinical prediction models (CPM; ie, statistically derived) in febrile young infants at risk for serious bacterial infections. A systematic literature review identified eight CPMs for predicting serious bacterial infections in febrile children. We validated these CPMs on four validation cohorts of febrile children in Spain (age <3 months), France (age <3 months) and two cohorts in the Netherlands (age 1-3 months and >3-12 months). We evaluated the performance of the CPMs by sensitivity/specificity, area under the receiver operating characteristic curve (AUC) and calibration studies. The original cohorts in which the prediction rules were developed (derivation cohorts) ranged from 381 to 15 781 children, with a prevalence of serious bacterial infections varying from 0.8% to 27% and spanned an age range of 0-16 years. All CPMs originally performed moderately to very well (AUC 0.60-0.93). The four validation cohorts included 159-2204 febrile children, with a median age range of 1.8 (1.2-2.4) months for the three cohorts <3 months and 8.4 (6.0-9.6) months for the cohort >3-12 months of age. The prevalence of serious bacterial infections varied between 15.1% and 17.2% in the three cohorts <3 months and was 9.8% for the cohort >3-12 months of age. Although discriminative values varied greatly, best performance was observed for four CPMs including clinical signs and symptoms, urine dipstick analyses and laboratory markers with AUC ranging from 0.68 to 0.94 in the three cohorts <3 months (ranges sensitivity: 0.48-0.94 and specificity: 0.71-0.97). For the >3-12 months' cohort AUC ranges from 0.80 to 0.89 (ranges sensitivity: 0.70-0.82 and specificity: 0.78-0.90). In general, the specificities exceeded sensitivities in our cohorts, in contrast to derivation cohorts with high sensitivities, although this effect was stronger in infants <3 months than in infants >3-12 months. We identified four CPMs, including clinical signs and symptoms, urine dipstick analysis and laboratory markers, which can aid clinicians in identifying serious bacterial infections. We suggest clinicians should use CPMs as an adjunctive clinical tool when assessing the risk of serious bacterial infections in febrile young infants. © 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.

Latent Variable Regression 4-Level Hierarchical Model Using Multisite Multiple-Cohorts Longitudinal Data. CRESST Report 801

ERIC Educational Resources Information Center

Choi, Kilchan

2011-01-01

This report explores a new latent variable regression 4-level hierarchical model for monitoring school performance over time using multisite multiple-cohorts longitudinal data. This kind of data set has a 4-level hierarchical structure: time-series observation nested within students who are nested within different cohorts of students. These…

Type 1 diabetes susceptibility alleles are associated with distinct alterations in the gut microbiota.

PubMed

Mullaney, Jane A; Stephens, Juliette E; Costello, Mary-Ellen; Fong, Cai; Geeling, Brooke E; Gavin, Patrick G; Wright, Casey M; Spector, Timothy D; Brown, Matthew A; Hamilton-Williams, Emma E

2018-02-17

Dysbiosis of the gut microbiota has been implicated in the pathogenesis of many autoimmune conditions including type 1 diabetes (T1D). It is unknown whether changes in the gut microbiota observed in T1D are due to environmental drivers, genetic risk factors, or both. Here, we have performed an analysis of associations between the gut microbiota and T1D genetic risk using the non-obese diabetic (NOD) mouse model of T1D and the TwinsUK cohort. Through the analysis of five separate colonies of T1D susceptible NOD mice, we identified similarities in NOD microbiome that were independent of animal facility. Introduction of disease protective alleles at the Idd3 and Idd5 loci (IL2, Ctla4, Slc11a1, and Acadl) resulted in significant alterations in the NOD microbiome. Disease-protected strains exhibited a restoration of immune regulatory pathways within the gut which could also be reestablished using IL-2 therapy. Increased T1D disease risk from IL-2 pathway loci in the TwinsUK cohort of human subjects resulted in some similar microbiota changes to those observed in the NOD mouse. These findings demonstrate for the first time that type 1 diabetes-associated genetic variants that restore immune tolerance to islet antigens also result in functional changes in the gut immune system and resultant changes in the microbiota.

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.

Historic cohort study in Montreal's fur industry.

PubMed

Guay, D; Siemiatycki, J

1987-01-01

A historic cohort mortality study was carried out among two groups of male workers in the Montreal fur industry: 263 dressers and dyers and 599 fur garment manufacturers. The first group is exposed to a very wide variety of chemicals used in tanning, cleaning, and dyeing fur, including substances considered to be carcinogenic and/or mutagenic. The second group is exposed to residue from the dressing and dyeing stage and to respirable fur dust. The cohorts consisted of all active members of two unions as of January 1, 1966. The mean age of the workers was 43.2 and the mean number of years since first employment 14.1. The follow-up period was from January 1, 1966, to December 31, 1981; 95% of the workers were successfully traced. Observed deaths were compared with those expected based on mortality rates of the population of metropolitan Montreal. Standardized mortality ratios (SMRs) for the manufacturers were significantly low, probably because of the ethnic composition of the cohort and a healthy worker effect. SMRs for the dressers and dyers were also low, but not as low as for the manufacturers. When attention was restricted to the French Canadians in the cohort, the observed deaths were close to the expected; there was a noteworthy excess of colorectal cancer (four observed, 0.8 expected) for dressers and dyers. Apart from this weak suggestive evidence, the results did not indicate any excess mortality risks in the fur industry. However, because of the relatively small number of expected and observed deaths in the cohort and especially among the heavily exposed dressers and dyers, the confidence intervals around SMR estimates were wide and excess risks cannot be ruled out.

Smoking habits and leukocyte telomere length dynamics among older adults: Results from the ESTHER cohort.

PubMed

Müezzinler, Aysel; Mons, Ute; Dieffenbach, Aida Karina; Butterbach, Katja; Saum, Kai-Uwe; Schick, Matthias; Stammer, Hermann; Boukamp, Petra; Holleczek, Bernd; Stegmaier, Christa; Brenner, Hermann

2015-10-01

Leukocyte telomere length (LTL) shortens with age and short LTL has been associated with increased mortality and increased risk for some age-related outcomes. This study aims to analyse the associations of smoking habits with LTL and rate of LTL change per year in older adults. LTL was measured by quantitative PCR at baseline in 3600 older adults, who were enrolled in a population-based cohort study in Germany. For longitudinal analyses, measurements were repeated in blood samples obtained at 8-year follow-up from 1000 participants. Terminal Restriction Fragment analysis was additionally performed in a sub-sample to obtain absolute LTL in base pairs. Multivariate linear regression models were used to estimate associations of smoking habits with baseline LTL and changes in LTL over time. LTL was inversely associated with age (r=-0.090, p<0.0001). Women had longer LTL than men (p<0.0001). Smoking was inversely associated with LTL. On average, current smokers had 73 base pairs (BP) shorter LTL compared to never smokers. Smoking intensity and pack-years of smoking were also inversely associated with LTL, and a positive association was observed with years since smoking cessation. Slower LTL attrition rates were observed in ever smokers over 8years of follow-up. Our cross-sectional analysis supports suggestions that smoking might contribute to shortening of LTL but this relationship could not be shown longitudinally. The overall rather small effect sizes observed for smoking-related variables suggest that LTL reflects smoking-related health hazards only to a very limited extent. Copyright © 2015 Elsevier Inc. All rights reserved.

Canadian breast implant cohort: extended follow-up of cancer incidence.

PubMed

Pan, Sai Yi; Lavigne, Eric; Holowaty, Eric J; Villeneuve, Paul J; Xie, Lin; Morrison, Howard; Brisson, Jacques

2012-10-01

Cosmetic breast implants are not associated with increased breast cancer incidence, but variations of risk according to implant characteristics are still poorly understood. As well, the assessment of cancer risk for sites other than breast needs to be clarified. The purpose of this study was to fill these research gaps. This study presents an extended analysis of 10 more years of follow-up of a large Canadian cohort of women who received either cosmetic breast implants (n = 24,558) or other cosmetic surgery (15,893). Over 70% of the implant cohort was followed for over 20 years. Cancer incidence among implant women was compared to those of controls using multivariate Poisson models and the general female population using the standardized incidence ratios (SIRs). Women with breast implants had reduced rates of breast and endometrial cancers compared to other surgery women. Subglandular implants were associated to a reduced rate of breast cancer compared to submuscular implants [incidence rate ratio (IRR) = 0.78, 95% confidence interval (CI) = 0.63-0.96] and this reduction persisted over time. We observed a sevenfold increased rate (IRR = 7.36, 95% CI = 1.86-29.12) of breast cancer in the first 5 years after the date of surgery for polyurethane-coated subglandular implant women but this IRR decreased progressively over time (p value for trend = 0.02). We also observed no increased risk of rarer forms of cancer among augmented women. A reduction in breast cancer incidence was observed for women with subglandular implants relative to women with submuscular implants. Possible increase of breast cancer incidence shortly after breast augmentation with polyurethane implants needs to be verified. Copyright © 2012 UICC.

Genetic polymorphisms in pre-miRNAs predict the survival of non-small-cell lung cancer in Chinese population: a cohort study and a meta-analysis

PubMed Central

Xia, Lingzi; Yin, Zhihua; Li, Xuelian; Ren, Yangwu; Zhang, Haibo; Zhao, Yuxia; Zhou, Baosen

2017-01-01

Background To explore the association of genetic polymorphisms in pre-miRNA 30c-1 rs928508 and pre-miRNA 27a rs895819 with non-small-cell lung cancer prognosis. Materials and Methods 480 patients from five hospitals were enrolled in this prospective cohort study. They were followed up for five years. The association between genotypes and overall survival was assessed by Cox proportional hazards regression models. A meta-analysis was conducted to provide evidence for the effect of microRNA 27a rs895819 on cancer survival. Results G-allele containing genotypes of microRNA 30c-1 polymorphisms and C-allele containing genotypes of microRNA 27a were significantly associated with poorer overall survival. Multivariate Cox regression models indicated that these genetic polymorhpisms were independently predictive factors of poorer overall survival. In stratified analysis, the effect was observed in many strata. The significant joint effect was also observed in our study. Patients with G allele of microRNA 30c-1 rs928508 and C allele of microRNA 27a rs895819 had the poorer overall survival than patients with C allele of rs928508 and T allele of rs895819. The effect of the microRNA 27a rs895819 on non-small cell lung cancer overall survival was supported by the meta-analysis results. Conclusions The two single nucleotide polymorphisms in microRNA 30c-1 and microRNA 27a can predict the outcome of non-small cell lung cancer patients and they may decrease the sensitivity to anti-cancer drugs. PMID:29100439

Mapping clinical outcomes expectations to treatment decisions: an application to vestibular schwannoma management.

PubMed

Cheung, Steven W; Aranda, Derick; Driscoll, Colin L W; Parsa, Andrew T

2010-02-01

Complex medical decision making obligates tradeoff assessments among treatment outcomes expectations, but an accessible tool to perform the necessary analysis is conspicuously absent. We aimed to demonstrate methodology and feasibility of adapting conjoint analysis for mapping clinical outcomes expectations to treatment decisions in vestibular schwannoma (VS) management. Prospective. Tertiary medical center and US-based otologists/neurotologists. Treatment preference profiles among VS stakeholders-61 younger and 74 older prospective patients, 61 observation patients, and 60 surgeons-were assessed for the synthetic VS case scenario of a 10-mm tumor in association with useful hearing and normal facial function. Treatment attribute utility. Conjoint analysis attribute levels were set in accordance to the results of a meta-analysis. Forty-five case series were disaggregated to formulate microsurgery facial nerve and hearing preservation outcomes expectations models. Attribute utilities were computed and mapped to the realistic treatment choices of translabyrinthine craniotomy, middle fossa craniotomy, and gamma knife radiosurgery. Among the treatment attributes of likelihoods of causing deafness, temporary facial weakness for 2 months, and incurable cancer within 20 years, and recovery time, permanent deafness was less important to tumor surgeons, and temporary facial weakness was more important to tumor surgeons and observation patients (Wilcoxon rank-sum, p < 0.001). Inverse mapping of preference profiles to realistic treatment choices showed all study cohorts were inclined to choose gamma knife radiosurgery. Mapping clinical outcomes expectations to treatment decisions for a synthetic clinical scenario revealed inhomogeneous drivers of choice selection among study cohorts. Medical decision engines that analyze personal preferences of outcomes expectations for VS and many other diseases may be developed to promote shared decision making among health care stakeholders and transparency in the informed consent process.

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.

Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group

PubMed Central

Pleyer, Lisa; Döhner, Hartmut; Dombret, Hervé; Seymour, John F.; Schuh, Andre C.; Beach, CL; Swern, Arlene S.; Burgstaller, Sonja; Stauder, Reinhard; Girschikofsky, Michael; Sill, Heinz; Schlick, Konstantin; Thaler, Josef; Halter, Britta; Machherndl Spandl, Sigrid; Zebisch, Armin; Pichler, Angelika; Pfeilstöcker, Michael; Autzinger, Eva M.; Lang, Alois; Geissler, Klaus; Voskova, Daniela; Sperr, Wolfgang R.; Hojas, Sabine; Rogulj, Inga M.; Andel, Johannes; Greil, Richard

2017-01-01

We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort; n = 214) with AAR patients meeting the same inclusion criteria (“AAR (001-like)” cohort; n = 95). The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (p = 0.616) for “AML-001” versus “AAR (001-like)” cohorts, respectively. Secondly, we pooled data from both cohorts (n = 309) and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6) months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (n = 95) versus all AAR patients with World Health Organization (WHO)-defined AML (“AAR (WHO-AML)” cohort; n = 193). Within the registry population, median OS for AAR patients meeting trial inclusion criteria versus all WHO-AML patients was 10.8 versus 11.8 months (p = 0.599), respectively. We thus tested and confirmed the efficacy of azacitidine as a front-line agent in patients with AML, >30% BM blasts and WBC ≤ 15 G/L in a routine clinical practice setting. We further show that the efficacy of azacitidine does not appear to be limited to AML patients who meet stringent clinical trial inclusion criteria, but instead appears efficacious as front-line treatment in all patients with WHO-AML. PMID:28212292

Acute Rejection in Renal Transplant Patients of a Hospital in Bogota, Colombia

PubMed Central

García, P.; Huerfano, M; Rodríguez, M; Caicedo, A; Berrío, F; Gonzalez, C

2016-01-01

Background: Renal transplantation is the best treatment for end stage renal disease. Acute graft rejection is one of the main complications and may influence graft survival. Objective: To determine the incidence and features of acute cellular rejection (ACR) episodes confirmed by biopsy. Methods: We studied a cohort of 175 patients who underwent renal transplantation between 2004 and 2012 to determine the cumulative incidence of ACR confirmed by biopsy and to identify the associated risk factors using multivariate analysis. Results: The one-year patient survival was 96.6%; the graft survival was 93.7%. The incidence of ACR within one year was 14.3%, of which 46% were observed within 6 months following transplantation. The most frequently observed ACR type was 1B according to the Banff classification system (42%). A relationship between ACR and receipt of a kidney from expanded criteria donors was observed, both in univariate and adjusted multiple log-binomial regression analyses, but only 6.3% of patients received extended criteria donor kidneys. No other relationships between variables were found. Conclusion: ACR frequency in this study was similar to that of other cohorts reported previously. We need a bigger sample of renal transplants from expanded criteria donors, PRA and DSA test to support the results. PMID:27721962

A model of risk and mental state shifts during social interaction.

PubMed

Hula, Andreas; Vilares, Iris; Lohrenz, Terry; Dayan, Peter; Montague, P Read

2018-02-01

Cooperation and competition between human players in repeated microeconomic games offer a window onto social phenomena such as the establishment, breakdown and repair of trust. However, although a suitable starting point for the quantitative analysis of such games exists, namely the Interactive Partially Observable Markov Decision Process (I-POMDP), computational considerations and structural limitations have limited its application, and left unmodelled critical features of behavior in a canonical trust task. Here, we provide the first analysis of two central phenomena: a form of social risk-aversion exhibited by the player who is in control of the interaction in the game; and irritation or anger, potentially exhibited by both players. Irritation arises when partners apparently defect, and it potentially causes a precipitate breakdown in cooperation. Failing to model one's partner's propensity for it leads to substantial economic inefficiency. We illustrate these behaviours using evidence drawn from the play of large cohorts of healthy volunteers and patients. We show that for both cohorts, a particular subtype of player is largely responsible for the breakdown of trust, a finding which sheds new light on borderline personality disorder.

A model of risk and mental state shifts during social interaction

PubMed Central

Vilares, Iris

2018-01-01

Cooperation and competition between human players in repeated microeconomic games offer a window onto social phenomena such as the establishment, breakdown and repair of trust. However, although a suitable starting point for the quantitative analysis of such games exists, namely the Interactive Partially Observable Markov Decision Process (I-POMDP), computational considerations and structural limitations have limited its application, and left unmodelled critical features of behavior in a canonical trust task. Here, we provide the first analysis of two central phenomena: a form of social risk-aversion exhibited by the player who is in control of the interaction in the game; and irritation or anger, potentially exhibited by both players. Irritation arises when partners apparently defect, and it potentially causes a precipitate breakdown in cooperation. Failing to model one’s partner’s propensity for it leads to substantial economic inefficiency. We illustrate these behaviours using evidence drawn from the play of large cohorts of healthy volunteers and patients. We show that for both cohorts, a particular subtype of player is largely responsible for the breakdown of trust, a finding which sheds new light on borderline personality disorder. PMID:29447153

Risk of cancer in an occupationally exposed cohort with increased level of chromosomal aberrations.

PubMed Central

Smerhovsky, Z; Landa, K; Rössner, P; Brabec, M; Zudova, Z; Hola, N; Pokorna, Z; Mareckova, J; Hurychova, D

2001-01-01

We used cytogenetic analysis to carry out a cohort study in which the major objective was to test the association between frequency of chromosomal aberrations and subsequent risk of cancer. In spite of the extensive use of the cytogenetic analysis of human peripheral blood lymphocytes in biomonitoring of exposure to various mutagens and carcinogens on an ecologic level, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed. In the present study, we analyzed data on 8,962 cytogenetic tests and 3,973 subjects. We found a significant and strong association between the frequency of chromosomal aberrations and cancer incidence in a group of miners exposed to radon, where a 1% increase in frequency of chromosomal aberrations was followed by a 64% increase in risk of cancer (p < 0.000). In contrast, the collected data are inadequate for a critical evaluation of the association with exposure to other chemicals. PMID:11171523

Surgical versus Non-Operative Treatment for Lumbar Disc Herniation: Eight-Year Results for the Spine Patient Outcomes Research Trial (SPORT)

PubMed Central

Lurie, Jon D.; Tosteson, Tor D.; Tosteson, Anna N. A.; Zhao, Wenyan; Morgan, Tamara S.; Abdu, William A.; Herkowitz, Harry; Weinstein, James N.

2014-01-01

Study Design Concurrent prospective randomized and observational cohort studies. Objective To assess the 8-year outcomes of surgery vs. non-operative care. Summary of Background Data Although randomized trials have demonstrated small short-term differences in favor of surgery, long-term outcomes comparing surgical to non-operative treatment remain controversial. Methods Surgical candidates with imaging-confirmed lumbar intervertebral disc herniation meeting SPORT eligibility criteria enrolled into prospective randomized (501 participants) and observational cohorts (743 participants) at 13 spine clinics in 11 US states. Interventions were standard open discectomy versus usual non-operative care. Main outcome measures were changes from baseline in the SF-36 Bodily Pain (BP) and Physical Function (PF) scales and the modified Oswestry Disability Index (ODI - AAOS/Modems version) assessed at 6 weeks, 3 and 6 months, and annually thereafter. Results Advantages were seen for surgery in intent-to-treat analyses for the randomized cohort for all primary and secondary outcomes other than work status; however, with extensive non-adherence to treatment assignment (49% patients assigned to non-operative therapy receiving surgery versus 60% of patients assigned to surgery) these observed effects were relatively small and not statistically significant for primary outcomes (BP, PF, ODI). Importantly, the overall comparison of secondary outcomes was significantly greater with surgery in the intent-to-treat analysis (sciatica bothersomeness [p > 0.005], satisfaction with symptoms [p > 0.013], and self-rated improvement [p > 0.013]) in long-term follow-up. An as-treated analysis showed clinically meaningful surgical treatment effects for primary outcome measures (mean change Surgery vs. Non-operative; treatment effect; 95% CI): BP (45.3 vs. 34.4; 10.9; 7.7 to 14); PF (42.2 vs. 31.5; 10.6; 7.7 to 13.5) and ODI (−36.2 vs. −24.8; −11.2; −13.6 to −9.1). Conclusion Carefully selected patients who underwent surgery for a lumbar disc herniation achieved greater improvement than non-operatively treated patients; there was little to no degradation of outcomes in either group (operative and non-operative) from 4 to 8 years. PMID:24153171

Trajectories of dental anxiety in a birth cohort

PubMed Central

Thomson, W. M.; Broadbent, J. M.; Locker, D.; Poulton, R.

2010-01-01

Objective To examine predictors of dental anxiety trajectories in a longitudinal study of New Zealanders. Methods Prospective study of a complete birth cohort born in 1972/73 in Dunedin, New Zealand, with dental anxiety scale (DAS) scores and dental utilization determined at ages 15, 18, 26 and 32 years. Personality traits were assessed at a superfactor and (more fine-grained) subscale level via the Multidimensional Personality Questionnaire at age 18 years. Group-based trajectory analysis was used to identify dental anxiety trajectories. Results DAS scores from at least three assessments were available for 828 participants. Six dental anxiety trajectories were observed: stable nonanxious low (39.6%); stable nonanxious medium (37.9%); recovery (1.6%); adult-onset anxious (7.7%); stable anxious (7.2%) and adolescent-onset anxious (5.9%). Multivariate analysis showed that males and those with higher DMFS at age 15 years were more likely to be in the stable nonanxious low trajectory group. Membership of the stable nonanxious medium group was predicted by the dental caries experience at age 15 years. Participants who had lost one or more teeth between ages 26 and 32 years had almost twice the relative risk for membership of the adult-onset anxious group. Personality traits predicted group membership. Specifically, high scorers (via median split) on the ‘stress reaction’ subscale had over twice the risk of being in the stable anxious group; low scorers on the traditionalism subscale were more likely to be members of the recovery trajectory group; and high scorers on the ‘social closeness’ subscale had half the risk of being in the stable anxious group. Dental caries experience at age 5 years was also a predictor for the stable anxious group. Membership of the late-adolescent-onset anxious group was predicted by higher dental caries experience by age 15 years, but none of the other predictors was significant. Conclusion Six discrete trajectories of dental anxiety have been observed. Some trajectories (totalling more than 90% of the cohort) had clear associations with external influences, but others were more strongly associated with characteristics such as personality traits. A mix of both influences was observed with only the stable anxious dental anxiety trajectory. PMID:19508269

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

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.

Personality Polygenes, Positive Affect, and Life Satisfaction

PubMed Central

Weiss, Alexander; Baselmans, Bart M. L.; Hofer, Edith; Yang, Jingyun; Okbay, Aysu; Lind, Penelope A.; Miller, Mike B.; Nolte, Ilja M.; Zhao, Wei; Hagenaars, Saskia P.; Hottenga, Jouke-Jan; Matteson, Lindsay K.; Snieder, Harold; Faul, Jessica D.; Hartman, Catharina A.; Boyle, Patricia A.; Tiemeier, Henning; Mosing, Miriam A.; Pattie, Alison; Davies, Gail; Liewald, David C.; Schmidt, Reinhold; De Jager, Philip L.; Heath, Andrew C.; Jokela, Markus; Starr, John M.; Oldehinkel, Albertine J.; Johannesson, Magnus; Cesarini, David; Hofman, Albert; Harris, Sarah E.; Smith, Jennifer A.; Keltikangas-Järvinen, Liisa; Pulkki-Råback, Laura; Schmidt, Helena; Smith, Jacqui; Iacono, William G.; McGue, Matt; Bennett, David A.; Pedersen, Nancy L.; Magnusson, Patrik K. E.; Deary, Ian J.; Martin, Nicholas G.; Boomsma, Dorret I.; Bartels, Meike; Luciano, Michelle

2016-01-01

Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of −0.49 and −0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains. PMID:27546527

A cohort study of mortality among Ontario pipe trades workers

PubMed Central

Finkelstein, M; Verma, D

2004-01-01

Aims: To study mortality in a cohort of members of the United Association of Journeymen and Apprentices of the Plumbing and Pipe Fitting Industry of the United States and Canada and to compare results with two previous proportional mortality studies. Methods: A cohort of 25 285 workers who entered the trade after 1949 was assembled from records of the international head office. Mortality was ascertained by linkage to the Canadian Mortality Registry at Statistics Canada. Standardised mortality ratios were computed using Ontario general population mortality rates as the reference. Results: There were significant increases in lung cancer mortality rates (SMR 1.27; 95% CI 1.13 to 1.42). Increased lung cancer risk was observed among plumbers, pipefitters, and sprinkler fitters. Increased risk was observed among workers joining the Union as late as the 1970s. A random effects meta-analysis of this study and the two PMR studies found significant increases in oesophageal (RR 1.24; 95% CI 1.00 to 1.53), lung (RR 1.31; 95% CI 1.19 to 1.44), and haematological/lymphatic (RR 1.21; 95% CI 1.08 to 1.35) malignancies. Conclusions: The mortality pattern is consistent with the effects of occupational exposure to asbestos. Increased risk due to other respiratory carcinogens such as welding fume cannot be excluded. There are substantial amounts of asbestos in place in industrial and commercial environments. The education and training of workers to protect themselves against inhalation hazards will be necessary well into the future. PMID:15317913

Environmental tobacco smoke exposure and health disparities: 8-year longitudinal findings from a large cohort of Thai adults.

PubMed

Tran, Thanh Tam; Yiengprugsawan, Vasoontara; Chinwong, Dujrudee; Seubsman, Sam-Ang; Sleigh, Adrian

2015-12-08

In rich countries, smokers, active or passive, often belong to disadvantaged groups. Less is known of tobacco patterns in the developing world. Hence, we seek out to investigate mental and physical health consequences of smoke exposure as well as tobacco-related inequality in transitional middle-income Thailand. We studied a nationwide cohort of 87,151 middle-aged and older adults that we have been following for eight years (2005-2013) for emerging chronic diseases. Logistic regression was used to identify attributes associated with passive smoke exposure. Longitudinal associations between smoke exposure and wellbeing (SF-8) or psychological distress (Kessler 6) were investigated with multiple linear regression or multivariate logistic regression analysis. A high proportion of cohort members, especially females, were passive smokers at home and at public transport stations; males were more exposed at workplace and recreational places. We observed a social gradient with more passive smoking in poorer people. We also observed a dose response relationship linking graded smoke exposures (current, former, passive, non-exposed) to less wellbeing and more psychological distress (p-trend < 0.001). Female smokers in general had less wellbeing and more distress. Our findings add to current knowledge on the impact of active and passive smoking on health in a transitional economy. Promotion of smoking cessation programs both in public and at home could also potentially reduce adverse disparities in health and wellbeing in middle and lower income settings such as Thailand.

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2016-01-01

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

Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms.

PubMed

van 't Hof, Femke N G; Ruigrok, Ynte M; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; de Andrade, Mariza; Baas, Annette F; Blankensteijn, Jan D; Böttinger, Erwin P; Bown, Matthew J; Broderick, Joseph; Bijlenga, Philippe; Carrell, David S; Crawford, Dana C; Crosslin, David R; Ebeling, Christian; Eriksson, Johan G; Fornage, Myriam; Foroud, Tatiana; von Und Zu Fraunberg, Mikael; Friedrich, Christoph M; Gaál, Emília I; Gottesman, Omri; Guo, Dong-Chuan; Harrison, Seamus C; Hernesniemi, Juha; Hofman, Albert; Inoue, Ituro; Jääskeläinen, Juha E; Jones, Gregory T; Kiemeney, Lambertus A L M; Kivisaari, Riku; Ko, Nerissa; Koskinen, Seppo; Kubo, Michiaki; Kullo, Iftikhar J; Kuivaniemi, Helena; Kurki, Mitja I; Laakso, Aki; Lai, Dongbing; Leal, Suzanne M; Lehto, Hanna; LeMaire, Scott A; Low, Siew-Kee; Malinowski, Jennifer; McCarty, Catherine A; Milewicz, Dianna M; Mosley, Thomas H; Nakamura, Yusuke; Nakaoka, Hirofumi; Niemelä, Mika; Pacheco, Jennifer; Peissig, Peggy L; Pera, Joanna; Rasmussen-Torvik, Laura; Ritchie, Marylyn D; Rivadeneira, Fernando; van Rij, Andre M; Santos-Cortez, Regie Lyn P; Saratzis, Athanasios; Slowik, Agnieszka; Takahashi, Atsushi; Tromp, Gerard; Uitterlinden, André G; Verma, Shefali S; Vermeulen, Sita H; Wang, Gao T; Han, Buhm; Rinkel, Gabriël J E; de Bakker, Paul I W

2016-07-14

Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single-nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10(-5)) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10(-3)). Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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.

Finasteride does not prevent bladder cancer: A secondary analysis of the Medical Therapy for Prostatic Symptoms Study.

PubMed

Sathianathen, Niranjan J; Fan, Yunhua; Jarosek, Stephanie L; Lawrentschuk, Nathan L; Konety, Badrinath R

2018-05-03

Preclinical models have demonstrated that androgen receptor modulation can influence bladder carcinogenesis with an inverse association observed between serum androgen levels and bladder cancer (BC) incidence. It is still unclear whether 5α-reductase inhibitors, by preventing the conversion of testosterone to dihydrotestosterone, have a similar effect. This study aims to evaluate whether dihydrotestosterone-mediated androgen activity has an impact on BC incidence in a cohort of men included in a clinical trial of finasteride vs. placebo with rigorous compliance monitoring. A secondary analysis was performed on all patients enrolled in the Medical Therapy for Prostatic Symptoms (MTOPS) Study and included in the biopsy substudy. Men were stratified into groups based on receiving finasteride and the incidence of BC compared between the groups. After exclusions for poor finasteride compliance (n = 338) and missing serum hormone results (n = 9), 2,700 men were eligible for analysis. In total, 0.8% (n = 18) of the cohort was diagnosed with BC during the trial period. There was no difference in the incidence of BC between men who received finasteride and those who did not (0.74% [n = 9] vs. 0.61% [n = 9], P = 0.67). Neither serum testosterone levels, prostate cancer diagnosis nor urinary bother (measured by International Prostate Symptom Score) demonstrated an association with BC diagnosis. These relationships were consistent in the subgroup of men in the biopsy substudy. There was no observable relationship between decreased dihydrotestosterone levels and BC diagnosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Association of prehospitalization aspirin therapy and acute lung injury: results of a multicenter international observational study of at-risk patients.

PubMed

Kor, Daryl J; Erlich, Jason; Gong, Michelle N; Malinchoc, Michael; Carter, Rickey E; Gajic, Ognjen; Talmor, Daniel S

2011-11-01

To evaluate the association between prehospitalization aspirin therapy and incident acute lung injury in a heterogeneous cohort of at-risk medical patients. This is a secondary analysis of a prospective multicenter international cohort investigation. Multicenter observational study including 20 US hospitals and two hospitals in Turkey. Consecutive, adult, nonsurgical patients admitted to the hospital with at least one major risk factor for acute lung injury. None. Baseline characteristics and acute lung injury risk factors/modifiers were identified. The presence of aspirin therapy and the propensity to receive this therapy were determined. The primary outcome was acute lung injury during hospitalization. Secondary outcomes included intensive care unit and hospital mortality and intensive care unit and hospital length of stay. Twenty-two hospitals enrolled 3855 at-risk patients over a 6-month period. Nine hundred seventy-six (25.3%) were receiving aspirin at the time of hospitalization. Two hundred forty (6.2%) patients developed acute lung injury. Univariate analysis noted a reduced incidence of acute lung injury in those receiving aspirin therapy (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.46-0.90; p = .010). This association was attenuated in a stratified analysis based on deciles of aspirin propensity scores (Cochran-Mantel-Haenszel pooled OR, 0.70; 95% CI, 0.48-1.03; p = .072). After adjusting for the propensity to receive aspirin therapy, no statistically significant associations between prehospitalization aspirin therapy and acute lung injury were identified; however, a prospective clinical trial to further evaluate this association appears warranted.

The association between the combined oral contraceptive pill and insulin resistance, dysglycemia and dyslipidemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of observational studies.

PubMed

Halperin, Ilana J; Kumar, Shoba Sujana; Stroup, Donna F; Laredo, Sheila E

2011-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of young women. First-line treatment is often the oral contraceptive pill (OC), but evidence suggests that OC may worsen metabolic outcomes in this population. We undertook this meta-analysis of observational studies and cohorts from within randomized controlled studies to investigate the association between OC use and dysglycemia, dyslipidemia and insulin resistance (IR) in women with PCOS. We searched MEDLINE (1966-April 2010), EMBASE (1980-April 2010) and All EBM Reviews. We included prospective cohorts and RCTs that treated women, aged 13-44, with PCOS with OC for at least 3 months. Blinded quality assessment and data extraction were conducted on 35 included studies by two independent reviewers. We used random effects methods to calculate weighted mean differences as the effect size. We investigated heterogeneity using sequential removal of studies, subgroup analysis and meta-regression. OC use was significantly associated with an increase in high-density lipoprotein cholesterol (HDL-C) (P = 0.004) and triglycerides (P = 0.004). Significant heterogeneity was found in glucose, cholesterol, HDL-C, low-density lipoprotein cholesterol triglycerides, fasting glucose to insulin ratios and homeostatic model assessments-IR. Study characteristics such as mean BMI, mean age and duration of study could explain some of the heterogeneity. Use of OC was not associated with clinically significant adverse metabolic consequences. Because of limitations of the underlying studies, further research including rigorously designed randomized trials would more definitively confirm our findings.

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

Prospective Dutch colorectal cancer cohort: an infrastructure for long-term observational, prognostic, predictive and (randomized) intervention research.

PubMed

Burbach, J P M; Kurk, S A; Coebergh van den Braak, R R J; Dik, V K; May, A M; Meijer, G A; Punt, C J A; Vink, G R; Los, M; Hoogerbrugge, N; Huijgens, P C; Ijzermans, J N M; Kuipers, E J; de Noo, M E; Pennings, J P; van der Velden, A M T; Verhoef, C; Siersema, P D; van Oijen, M G H; Verkooijen, H M; Koopman, M

2016-11-01

Systematic evaluation and validation of new prognostic and predictive markers, technologies and interventions for colorectal cancer (CRC) is crucial for optimizing patients' outcomes. With only 5-15% of patients participating in clinical trials, generalizability of results is poor. Moreover, current trials often lack the capacity for post-hoc subgroup analyses. For this purpose, a large observational cohort study, serving as a multiple trial and biobanking facility, was set up by the Dutch Colorectal Cancer Group (DCCG). The Prospective Dutch ColoRectal Cancer cohort is a prospective multidisciplinary nationwide observational cohort study in the Netherlands (yearly CRC incidence of 15 500). All CRC patients (stage I-IV) are eligible for inclusion, and longitudinal clinical data are registered. Patients give separate consent for the collection of blood and tumor tissue, filling out questionnaires, and broad randomization for studies according to the innovative cohort multiple randomized controlled trial design (cmRCT), serving as an alternative study design for the classic RCT. Objectives of the study include: 1) systematically collected long-term clinical data, patient-reported outcomes and biomaterials from daily CRC practice; and 2) to facilitate future basic, translational and clinical research including interventional and cost-effectiveness studies for both national and international research groups with short inclusion periods, even for studies with stringent inclusion criteria. Seven months after initiation 650 patients have been enrolled, eight centers participate, 15 centers await IRB approval and nine embedded cohort- or cmRCT-designed studies are currently recruiting patients. This cohort provides a unique multidisciplinary data, biobank, and patient-reported outcomes collection initiative, serving as an infrastructure for various kinds of research aiming to improve treatment outcomes in CRC patients. This comprehensive design may serve as an example for other tumor types.

A review of published analyses of case-cohort studies and recommendations for future reporting.

PubMed

Sharp, Stephen J; Poulaliou, Manon; Thompson, Simon G; White, Ian R; Wood, Angela M

2014-01-01

The case-cohort study design combines the advantages of a cohort study with the efficiency of a nested case-control study. However, unlike more standard observational study designs, there are currently no guidelines for reporting results from case-cohort studies. Our aim was to review recent practice in reporting these studies, and develop recommendations for the future. By searching papers published in 24 major medical and epidemiological journals between January 2010 and March 2013 using PubMed, Scopus and Web of Knowledge, we identified 32 papers reporting case-cohort studies. The median subcohort sampling fraction was 4.1% (interquartile range 3.7% to 9.1%). The papers varied in their approaches to describing the numbers of individuals in the original cohort and the subcohort, presenting descriptive data, and in the level of detail provided about the statistical methods used, so it was not always possible to be sure that appropriate analyses had been conducted. Based on the findings of our review, we make recommendations about reporting of the study design, subcohort definition, numbers of participants, descriptive information and statistical methods, which could be used alongside existing STROBE guidelines for reporting observational studies.

A Severe Sepsis Mortality Prediction Model and Score for Use with Administrative Data

PubMed Central

Ford, Dee W.; Goodwin, Andrew J.; Simpson, Annie N.; Johnson, Emily; Nadig, Nandita; Simpson, Kit N.

2016-01-01

Objective Administrative data is used for research, quality improvement, and health policy in severe sepsis. However, there is not a sepsis-specific tool applicable to administrative data with which to adjust for illness severity. Our objective was to develop, internally validate, and externally validate a severe sepsis mortality prediction model and associated mortality prediction score. Design Retrospective cohort study using 2012 administrative data from five US states. Three cohorts of patients with severe sepsis were created: 1) ICD-9-CM codes for severe sepsis/septic shock, 2) ‘Martin’ approach, and 3) ‘Angus’ approach. The model was developed and internally validated in ICD-9-CM cohort and externally validated in other cohorts. Integer point values for each predictor variable were generated to create a sepsis severity score. Setting Acute care, non-federal hospitals in NY, MD, FL, MI, and WA Subjects Patients in one of three severe sepsis cohorts: 1) explicitly coded (n=108,448), 2) Martin cohort (n=139,094), and 3) Angus cohort (n=523,637) Interventions None Measurements and Main Results Maximum likelihood estimation logistic regression to develop a predictive model for in-hospital mortality. Model calibration and discrimination assessed via Hosmer-Lemeshow goodness-of-fit (GOF) and C-statistics respectively. Primary cohort subset into risk deciles and observed versus predicted mortality plotted. GOF demonstrated p>0.05 for each cohort demonstrating sound calibration. C-statistic ranged from low of 0.709 (sepsis severity score) to high of 0.838 (Angus cohort) suggesting good to excellent model discrimination. Comparison of observed versus expected mortality was robust although accuracy decreased in highest risk decile. Conclusions Our sepsis severity model and score is a tool that provides reliable risk adjustment for administrative data. PMID:26496452

Impact of frequent cerebrospinal fluid sampling on Aβ levels: systematic approach to elucidate influencing factors.

PubMed

Van Broeck, Bianca; Timmers, Maarten; Ramael, Steven; Bogert, Jennifer; Shaw, Leslie M; Mercken, Marc; Slemmon, John; Van Nueten, Luc; Engelborghs, Sebastiaan; Streffer, Johannes Rolf

2016-05-19

Cerebrospinal fluid (CSF) amyloid-beta (Aβ) peptides are predictive biomarkers for Alzheimer's disease and are proposed as pharmacodynamic markers for amyloid-lowering therapies. However, frequent sampling results in fluctuating CSF Aβ levels that have a tendency to increase compared with baseline. The impact of sampling frequency, volume, catheterization procedure, and ibuprofen pretreatment on CSF Aβ levels using continuous sampling over 36 h was assessed. In this open-label biomarker study, healthy participants (n = 18; either sex, age 55-85 years) were randomized into one of three cohorts (n = 6/cohort; high-frequency sampling). In all cohorts except cohort 2 (sampling started 6 h post catheterization), sampling through lumbar catheterization started immediately post catheterization. Cohort 3 received ibuprofen (800 mg) before catheterization. Following interim data review, an additional cohort 4 (n = 6) with an optimized sampling scheme (low-frequency and lower volume) was included. CSF Aβ(1-37), Aβ(1-38), Aβ(1-40), and Aβ(1-42) levels were analyzed. Increases and fluctuations in mean CSF Aβ levels occurred in cohorts 1-3 at times of high-frequency sampling. Some outliers were observed (cohorts 2 and 3) with an extreme pronunciation of this effect. Cohort 4 demonstrated minimal fluctuation of CSF Aβ both on a group and an individual level. Intersubject variability in CSF Aβ profiles over time was observed in all cohorts. CSF Aβ level fluctuation upon catheterization primarily depends on the sampling frequency and volume, but not on the catheterization procedure or inflammatory reaction. An optimized low-frequency sampling protocol minimizes or eliminates fluctuation of CSF Aβ levels, which will improve the capability of accurately measuring the pharmacodynamic read-out for amyloid-lowering therapies. ClinicalTrials.gov NCT01436188 . Registered 15 September 2011.

The impact of breast cancer-specific birth cohort effects among younger and older Chinese populations.

PubMed

Sung, Hyuna; Rosenberg, Philip S; Chen, Wan-Qing; Hartman, Mikael; Lim, Wei-Yen; Chia, Kee Seng; Wai-Kong Mang, Oscar; Tse, Lapah; Anderson, William F; Yang, Xiaohong R

2016-08-01

Historically low breast cancer incidence rates among Asian women have risen worldwide; purportedly due to the adoption of a "Western" life style among younger generations (i.e., the more recent birth cohorts). However, no study has simultaneously compared birth cohort effects between both younger and older women in different Asian and Western populations. Using cancer registry data from rural and urban China, Singapore and the United States (1990-2008), we estimated age-standardized incidence rates (ASR), annual percentage change (EAPC) in the ASR, net drifts, birth cohort specific incidence rates and cohort rate ratios (CRR). Younger (30-49 years, 1943-1977 birth cohorts) and older women (50-79 years; 1913-1957 birth cohorts) were assessed separately. CRRs among Chinese populations were estimated using birth cohort specific rates with US non-Hispanic white women (NHW) serving as the reference population with an assigned CRR of 1.0. We observed higher EAPCs and net drifts among those Chinese populations with lower ASRs. Similarly, we observed the most rapidly increasing cohort-specific incidence rates among those Chinese populations with the lowest baseline CRRs. Both trends were more significant among older than younger women. Average CRRs were 0.06-0.44 among older and 0.18-0.81 among younger women. Rapidly rising cohort specific rates have narrowed the historic disparity between Chinese and US NHW breast cancer populations particularly in regions with the lowest baseline rates and among older women. Future analytic studies are needed to investigate risk factors accounting for the rapid increase of breast cancer among older and younger women separately in Asian populations. © 2016 UICC.

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.

Safety of quadrivalent live attenuated influenza vaccine in subjects aged 2-49years.

PubMed

Baxter, Roger; Eaton, Abigail; Hansen, John; Aukes, Laurie; Caspard, Herve; Ambrose, Christopher S

2017-03-01

Quadrivalent live attenuated influenza vaccine (Q/LAIV) was licensed in 2012 and replaced trivalent live attenuated influenza vaccine in the United States during the 2013-2014 influenza season. This study assessed the safety of Q/LAIV in children and adults aged 2-49years. This was a prospective observational cohort study using data collected from Kaiser Permanente Northern California. Post-vaccination events of interest were any hospitalization, hospitalization for lower respiratory tract infection, and the following medically attended events: hypersensitivity, seizures/convulsions, lower respiratory tract infection, wheezing, Guillain-Barré syndrome, Bell's palsy, encephalitis, neuritis, vasculitis, and narcolepsy/cataplexy. The rates of these events during the risk interval post-vaccination were compared with rates observed during reference periods later in the follow-up (within-cohort analysis) and with rates observed in frequency-matched unvaccinated controls and inactivated influenza vaccine (IIV) recipients. A total of 62,040 eligible Q/LAIV recipients were identified during the 2013-2014 influenza season. Within-cohort comparisons of all Q/LAIV recipients as well as comparisons between Q/LAIV recipients and unvaccinated controls or IIV recipients did not show any significantly higher risk of hospitalizations or medically attended events following administration of Q/LAIV. Additional analyses by setting (clinic visits, emergency department visits, and hospital admissions) and age group (2-4, 5-8, 9-17, and 18-49years) also did not reveal clinically consistent findings that suggested any increased risk after administration of Q/LAIV. In this large population study of individuals aged 2-49years, no safety signals associated with the administration of Q/LAIV were observed. A much larger study population would be needed to confidently reject any association between Q/LAIV and very rare events, specifically those with an incidence of <1 event/10,000 person-years. ClinicalTrials.gov NCT01985997. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

The rare TREM2 R47H variant exerts only a modest effect on Alzheimer disease risk.

PubMed

Hooli, Basavaraj V; Parrado, Antonio R; Mullin, Kristina; Yip, Wai-Ki; Liu, Tian; Roehr, Johannes T; Qiao, Dandi; Jessen, Frank; Peters, Oliver; Becker, Tim; Ramirez, Alfredo; Lange, Christoph; Bertram, Lars; Tanzi, Rudolph E

2014-10-07

Recently, 2 independent studies reported that a rare missense variant, rs75932628 (R47H), in exon 2 of the gene encoding the "triggering receptor expressed on myeloid cells 2" (TREM2) significantly increases the risk of Alzheimer disease (AD) with an effect size comparable to that of the APOE ε4 allele. In this study, we attempted to replicate the association between rs75932628 and AD risk by directly genotyping rs75932628 in 2 independent Caucasian family cohorts consisting of 927 families (with 1,777 affected and 1,235 unaffected) and in 2 Caucasian case-control cohorts composed of 1,314 cases and 1,609 controls. In addition, we imputed genotypes in 3 independent Caucasian case-control cohorts containing 1,906 cases and 1,503 controls. Meta-analysis of the 2 family-based and the 5 case-control cohorts yielded a p value of 0.0029, while the overall summary estimate (using case-control data only) resulted in an odds ratio of 1.67 (95% confidence interval 0.95-2.92) for the association between the TREM2 R47H and increased AD risk. While our results serve to confirm the association between R47H and risk of AD, the observed effect on risk was substantially smaller than that previously reported. © 2014 American Academy of Neurology.

The rare TREM2 R47H variant exerts only a modest effect on Alzheimer disease risk

PubMed Central

Hooli, Basavaraj V.; Parrado, Antonio R.; Mullin, Kristina; Yip, Wai-Ki; Liu, Tian; Roehr, Johannes T.; Qiao, Dandi; Jessen, Frank; Peters, Oliver; Becker, Tim; Ramirez, Alfredo; Lange, Christoph; Bertram, Lars

2014-01-01

Objectives: Recently, 2 independent studies reported that a rare missense variant, rs75932628 (R47H), in exon 2 of the gene encoding the “triggering receptor expressed on myeloid cells 2” (TREM2) significantly increases the risk of Alzheimer disease (AD) with an effect size comparable to that of the APOE ε4 allele. Methods: In this study, we attempted to replicate the association between rs75932628 and AD risk by directly genotyping rs75932628 in 2 independent Caucasian family cohorts consisting of 927 families (with 1,777 affected and 1,235 unaffected) and in 2 Caucasian case-control cohorts composed of 1,314 cases and 1,609 controls. In addition, we imputed genotypes in 3 independent Caucasian case-control cohorts containing 1,906 cases and 1,503 controls. Results: Meta-analysis of the 2 family-based and the 5 case-control cohorts yielded a p value of 0.0029, while the overall summary estimate (using case-control data only) resulted in an odds ratio of 1.67 (95% confidence interval 0.95–2.92) for the association between the TREM2 R47H and increased AD risk. Conclusions: While our results serve to confirm the association between R47H and risk of AD, the observed effect on risk was substantially smaller than that previously reported. PMID:25186855

A population-based analysis of increasing rates of suicide mortality in Japan and South Korea, 1985-2010.

PubMed

Jeon, Sun Y; Reither, Eric N; Masters, Ryan K

2016-04-23

In the past two decades, rates of suicide mortality have declined among most OECD member states. Two notable exceptions are Japan and South Korea, where suicide mortality has increased by 20 % and 280 %, respectively. Population and suicide mortality data were collected through national statistics organizations in Japan and South Korea for the period 1985 to 2010. Age, period of observation, and birth cohort membership were divided into five-year increments. We fitted a series of intrinsic estimator age-period-cohort models to estimate the effects of age-related processes, secular changes, and birth cohort dynamics on the rising rates of suicide mortality in the two neighboring countries. In Japan, elevated suicide rates are primarily driven by period effects, initiated during the Asian financial crisis of the late 1990s. In South Korea, multiple factors appear to be responsible for the stark increase in suicide mortality, including recent secular changes, elevated suicide risks at older ages in the context of an aging society, and strong cohort effects for those born between the Great Depression and the aftermath of the Korean War. In spite of cultural, demographic and geographic similarities in Japan and South Korea, the underlying causes of increased suicide mortality differ across these societies-suggesting that public health responses should be tailored to fit each country's unique situation.

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

The association of birth order with later body mass index and blood pressure: a comparison between prospective cohort studies from the United Kingdom and Brazil.

PubMed

Howe, L D; Hallal, P C; Matijasevich, A; Wells, J C; Santos, I S; Barros, A J D; Lawlor, D A; Victora, C G; Smith, G D

2014-07-01

Previous studies have found greater adiposity and cardiovascular risk in first born children. The causality of this association is not clear. Examining the association in diverse populations may lead to improved insight. We examine the association between birth order and body mass index (BMI), systolic and diastolic blood pressure (SBP/DBP) in the 2004 Pelotas cohort from southern Brazil and the Avon Longitudinal Study of Parents and Children (ALSPAC) from Bristol, south-west England, restricting analysis to families with two children in order to remove confounding by family size. No consistent differences in BMI, SBP or DBP were observed comparing first and second born children. Within the Pelotas 2004 cohort, first born females were thinner, with lower SBP and DBP; for example, mean difference in SBP comparing first with second born was -0.979 (95% confidence interval -2.901 to 0.943). In ALSPAC, first born females had higher BMI, SBP and DBP. In both cohorts, associations tended to be in the opposite direction in males, although no statistical evidence for gender interactions was found. The findings do not support an association between birth order and BMI or blood pressure. Differences to previous studies may be explained by differences in populations and/or confounding by family size in previous studies.

Fruit and Vegetable Consumption and Changes in Anthropometric Variables in Adult Populations: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

PubMed Central

Schwingshackl, Lukas; Hoffmann, Georg; Kalle-Uhlmann, Tamara; Arregui, Maria; Buijsse, Brian; Boeing, Heiner

2015-01-01

Background Randomized controlled trials provide conflicting results on the effects of increased fruit and vegetable consumption on changes in body weight. We aimed to perform a systematic review and meta-analysis of prospective cohort studies on fruit and vegetable consumption in relation to changes in anthropometric measures. Methods PubMed and EMBASE were searched up to July 2015 for prospective studies reporting on habitual fruit and/or vegetable consumption in relation to changes in body weight or waist circumference or to risk of weight gain/overweight/obesity in adults. Random-effects meta-analysis was applied to pool results across studies. Findings Seventeen cohort studies (from 20 reports) including 563,277 participants met our inclusion criteria. Higher intake of fruits was inversely associated with weight change (decrease) (beta-coefficient per 100-g increment, -13.68 g/year; 95% CI, -22.97 to -4.40). No significant changes could be observed for combined fruit and vegetable consumption or vegetable consumption. Increased intake of fruits was inversely associated with changes (decrease) in waist circumference (beta: -0.04 cm/year; 95% CI, -0.05 to -0.02). Comparing the highest combined fruit & vegetable, fruit, and vegetable intake categories were associated with a 9%, 17%, and 17% reduced risk of adiposity (odds ratio [OR]: 0.91, 95% CI, 0.84 to 0.99), (OR: 0.83, 95% CI, 0.71 to 0.99), and (OR: 0.83, 95% CI, 0.70 to 0.99), respectively. Conclusion This meta-analysis showed several inverse associations between fruit and vegetable intake and prospective improvements in anthropometric parameters, and risk of adiposity. The present meta-analysis seems to be limited by low study quality. Nevertheless, when combined with evolutionary nutrition and epidemiological modeling studies, these findings have public health relevance and support all initiatives to increase fruit and vegetable intake. PMID:26474158

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.

Impact of the Data Collection on Adverse Events of Anti-HIV Drugs cohort study on abacavir prescription among treatment-naive, HIV-infected patients in Canada.

PubMed

Antoniou, Tony; Gillis, Jennifer; Loutfy, Mona R; Cooper, Curtis; Hogg, Robert S; Klein, Marina B; Machouf, Nima; Montaner, Julio S G; Rourke, Sean B; Tsoukas, Chris; Raboud, Janet M

2014-01-01

To evaluate the trends in abacavir (ABC) prescription among antiretroviral (ARV) medication-naive individuals following the presentation of the Data Collection on Adverse Events of Anti-HIV Drugs (DAD) cohort study. We conducted a retrospective cohort study of ARV medication-naive individuals in the Canadian Observational Cohort (CANOC). Between January 1, 2000, and February 28, 2010, a total of 7280 ARV medication-naive patients were included in CANOC. We observed a significant change in the proportion of new ABC prescriptions immediately following the release of DAD (-11%; 95% confidence interval [CI]: -20% to -2.4%) and in the months following the presentation of these data (-0.66% per month; 95% CI: -1.2% to -0.073%). A post-DAD presentation decrease in the odds of being prescribed ABC versus tenofovir (TDF) was observed (adjusted odds ratio, 0.72 per year, 95% CI: 0.54-0.97). Presentation of the DAD was associated with a significant decrease in ABC use among ARV medication-naive, HIV-positive patients initiating therapy.

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…

Common Co-activation of AXL and CDCP1 in EGFR-mutation-positive Non-smallcell Lung Cancer Associated With Poor Prognosis.

PubMed

Karachaliou, Niki; Chaib, Imane; Cardona, Andres Felipe; Berenguer, Jordi; Bracht, Jillian Wilhelmina Paulina; Yang, Jie; Cai, Xueting; Wang, Zhigang; Hu, Chunping; Drozdowskyj, Ana; Servat, Carles Codony; Servat, Jordi Codony; Ito, Masaoki; Attili, Ilaria; Aldeguer, Erika; Capitan, Ana Gimenez; Rodriguez, July; Rojas, Leonardo; Viteri, Santiago; Molina-Vila, Miguel Angel; Ou, Sai-Hong Ignatius; Okada, Morihito; Mok, Tony S; Bivona, Trever G; Ono, Mayumi; Cui, Jean; Cajal, Santiago Ramón Y; Frias, Alex; Cao, Peng; Rosell, Rafael

2018-03-01

Epidermal growth factor receptor (EGFR)-mutation-positive non-smallcell lung cancer (NSCLC) is incurable, despite high rates of response to EGFR tyrosine kinase inhibitors (TKIs). We investigated receptor tyrosine kinases (RTKs), Src family kinases and focal adhesion kinase (FAK) as genetic modifiers of innate resistance in EGFR-mutation-positive NSCLC. We performed gene expression analysis in two cohorts (Cohort 1 and Cohort 2) of EGFR-mutation-positive NSCLC patients treated with EGFR TKI. We evaluated the efficacy of gefitinib or osimertinib with the Src/FAK/Janus kinase 2 (JAK2) inhibitor, TPX0005 in vitro and in vivo. In Cohort 1, CUB domain-containing protein-1 (CDCP1) was an independent negative prognostic factor for progression-free survival (hazard ratio of 1.79, p=0.0407) and overall survival (hazard ratio of 2.23, p=0.0192). A two-gene model based on AXL and CDCP1 expression was strongly associated with the clinical outcome to EGFR TKIs, in both cohorts of patients. Our preclinical experiments revealed that several RTKs and non-RTKs, were up-regulated at baseline or after treatment with gefitinib or osimertinib. TPX-0005 plus EGFR TKI suppressed expression and activation of RTKs and downstream signaling intermediates. Co-expression of CDCP1 and AXL is often observed in EGFR-mutation-positive tumors, limiting the efficacy of EGFR TKIs. Co-treatment with EGFR TKI and TPX-0005 warrants testing. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Prognostic nomogram for patients with hepatocellular carcinoma underwent adjuvant transarterial chemoembolization following curative resection

PubMed Central

Jing, Chu-Yu; Fu, Yi-Peng; Zheng, Su-Su; Yi, Yong; Shen, Hu-Jia; Huang, Jin-Long; Xu, Xin; Lin, Jia-Jia; Zhou, Jian; Fan, Jia; Ren, Zheng-Gang; Qiu, Shuang-Jian; Zhang, Bo-Heng

2017-01-01

Abstract Adjuvant transarterial chemoembolization (TACE) is a major option for postoperative hepatocellular carcinoma (HCC) patients with recurrence risk factors. However, individualized predictive models for subgroup of these patients are limited. This study aimed to develop a prognostic nomogram for patients with HCC underwent adjuvant TACE following curative resection. A cohort comprising 144 HCC patients who received adjuvant TACE following curative resection in the Zhongshan Hospital were analyzed. The nomogram was formulated based on independent prognostic indicators for overall survival (OS). The performance of the nomogram was evaluated by the concordance index (C-index), calibration curve, and decision curve analysis (DCA) and compared with the conventional staging systems. The results were validated in an independent cohort of 86 patients with the same inclusion criteria. Serum alpha-fetoprotein (AFP), hyper-sensitive C-reactive protein (hs-CRP), incomplete tumor encapsulation, and double positive staining of Cytokeratin 7 and Cytokeratin 19 on tumor cells were identified as independent predictors for OS. The C-indices of the nomogram for OS prediction in the training cohort and validation cohort were 0.787 (95%CI 0.775–0.799) and 0.714 (95%CI 0.695–0.733), respectively. In both the training and validation cohorts, the calibration plot showed good consistency between the nomogram-predicted and the observed survival. Furthermore, the established nomogram was superior to the conventional staging systems in terms of C-index and clinical net benefit on DCA. The proposed nomogram provided an accurate prediction on risk stratification for HCC patients underwent adjuvant TACE following curative resection. PMID:28296727

Association between renin–angiotensin–aldosterone system blockade and future osteoporotic fracture risk in hypertensive population

PubMed Central

Chen, Chang-I.; Yeh, Jong-Shiuan; Tsao, Nai-Wen; Lin, Fen-Yen; Shih, Chun-Ming; Chiang, Kuang-Hsing; Kao, Yung-Ta; Fang, Yu-Ann; Tsai, Lung-Wen; Liu, Wen-Chi; Nakagami, Hironori; Morishita, Ryuichi; Kuo, Yi-Jie; Huang, Chun-Yao

2017-01-01

Abstract Tissue renin–angiotensin–aldosterone system (RAAS) activation in sites of osteoporosis had been demonstrated in animal studies; however, the possibility of RAAS blockade to prevent future osteoporotic fracture had rarely been verified in clinical studies. We Used the Taiwan Longitudinal Health insurance database 2000 to 2008, the cohort study comprised patients age over 40 with a recorded new diagnosis of hypertension between January 1, 2000 to December 31, 2008, in addition, patients who had diagnosis of osteoporosis before the date of cohort enter were excluded. After the definite diagnosis of hypertension, each patient was followed until osteoporotic fracture happened or the end of 2008. The occurrence of osteoporotic fracture was evaluated in patients who either were or without taking RAAS blockade agents. Cox proportional hazard regressions were used to evaluate the osteoporotic fracture incidence after adjusting for known confounding factors. In total, 57,132 hypertensive patients comprised the study cohort. Our study results showed that the incidence of osteoporosis fracture in the whole cohort was significantly higher in the RAAS blockade non-user group than the user group. This phenomenon was observed in both sex and all age categories. Sensitivity analysis further showed the concordant lower osteoporosis fracture risk in patients with various RAAS blockers usage durations; the risk of osteoporosis fracture was the lowest in those drug use >365 days when compared with the non-user cohort. In conclusion, our study result demonstrated the lower future osteoporotic fracture risk in hypertensive subjects who received long term RAAS blocker treatment. PMID:29145244

Do changing levels of maternal exercise during pregnancy affect neonatal adiposity? Secondary analysis of the babies after SCOPE: evaluating the longitudinal impact using neurological and nutritional endpoints (BASELINE) birth cohort (Cork, Ireland).

PubMed

Norris, Tom; McCarthy, Fergus P; Khashan, Ali S; Murray, Deidre M; Kiely, Mairead; Hourihane, Jonathan O'B; Baker, Philip N; Kenny, Louise C

2017-12-01

To investigate whether changing levels of exercise during pregnancy are related to altered neonatal adiposity. Secondary analysis of data from a prospective cohort study. Cork, Ireland. 1200 mother - infant pairs recruited as part of a prospective birth cohort, Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE). Neonatal adiposity was assessed within several days of birth using air displacement plethysmography (PEAPOD). Per cent body fat (BF%) as a continuous outcome and a pair of dichotomous variables; high or low adiposity, representing BF% >90th or <10th centile, respectively. Multivariable linear and logistic regression models were used to investigate the relationship between exercise and the respective outcomes. Crude analysis revealed no association between a changing level of exercise (since becoming pregnant) at 15 weeks' gestation and any of the outcomes (BF%, low adiposity and high adiposity). At 20 weeks' gestation, analyses revealed that relative to women who do not change their exercise level up to 20 weeks, those women who decreased their exercise level were more likely to give birth to a neonate with adiposity above the 90th centile (OR 1.62, 95% CI 1.07 to 2.46). This association was maintained after adjustment for putative confounders (OR 1.62, 95% CI 1.06 to 2.47). We observed a possible critical period for the association between changing exercise levels and neonatal adiposity, with no association observed with exercise recall for the first 15 weeks of gestation, but an association with a decreasing level of exercise between 15 and 20 weeks. These results should be interpreted in line with the limitations of the study and further studies utilising objectively measured estimates of exercise are required in order to replicate these findings. NCT01498965. © 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.

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.

Human Fetuin-A Rs4918 Polymorphism and its Association with Obesity in Healthy Persons and in Patients with Myocardial Infarction in Two Hungarian Cohorts.

PubMed

Temesszentandrási, György; Vörös, Krisztián; Márkus, Bernadett; Böröcz, Zoltán; Kaszás, Edit; Prohászka, Zoltán; Falus, András; Cseh, Károly; Kalabay, László

2016-08-04

BACKGROUND Human fetuin A (AHSG) has been associated with the development of obesity, insulin resistance, type 2 diabetes mellitus, and atherosclerosis. Observations on the role of AHSG rs4918 single-nucleotide polymorphism are contradictory. We investigated the association between variants of rs4918 and parameters of obesity, lipid status, tumor necrosis factor-α (TNFα), adipokines (adiponectin, resistin, leptin), and insulin resistance in healthy persons and in patients with previous myocardial infarction. MATERIAL AND METHODS This was a cross-sectional study comprising cohort 1 (81 healthy individuals) and cohort 2 (157 patients with previous myocardial infarction). We used the allele-specific KASP genotyping assay to detect rs4918 polymorphism. RESULTS In cohort 1, G-nucleotide carriers had significantly lower serum TNFα, adiponectin, and higher leptin concentrations than in non-G carriers. These differences, however, were not observed in cohort 2. In cohort 2, G-carriers had lower BMI and waist circumferences than in non-G carriers. The G allele was more frequent among lean than obese patients (RR=1.067, 95%CI=1.053-2.651, p=0.015). An association between BMI and rs4918 polymorphism was observed among patients without diabetes (CC/CG/GG genotypes: p=0.003, G vs. non-G allele: p=0.008) but not in diabetics. In addition, a strong linearity between BMI and the CC/CG/GG genotypes (association value: 4.416, p=0.036) and the frequency of the G allele (7.420, p=0.006) could be identified. In cohort 2, non-obese, non-diabetic G-carriers still had lower BMI and waist circumferences than in non-G carriers. CONCLUSIONS The rs4918 minor variant is associated with lower TNFα and adiponectin, higher leptin levels in healthy persons, and more favorable anthropomorphic parameters of obesity in cohort 2.

Human Fetuin-A Rs4918 Polymorphism and its Association with Obesity in Healthy Persons and in Patients with Myocardial Infarction in Two Hungarian Cohorts

PubMed Central

Temesszentandrási, György; Vörös, Krisztián; Márkus, Bernadett; Böröcz, Zoltán; Kaszás, Edit; Prohászka, Zoltán; Falus, András; Cseh, Károly; Kalabay, László

2016-01-01

Background Human fetuin A (AHSG) has been associated with the development of obesity, insulin resistance, type 2 diabetes mellitus, and atherosclerosis. Observations on the role of AHSG rs4918 single-nucleotide polymorphism are contradictory. We investigated the association between variants of rs4918 and parameters of obesity, lipid status, tumor necrosis factor-α (TNFα), adipokines (adiponectin, resistin, leptin), and insulin resistance in healthy persons and in patients with previous myocardial infarction. Material/Methods This was a cross-sectional study comprising cohort 1 (81 healthy individuals) and cohort 2 (157 patients with previous myocardial infarction). We used the allele-specific KASP genotyping assay to detect rs4918 polymorphism. Results In cohort 1, G-nucleotide carriers had significantly lower serum TNFα, adiponectin, and higher leptin concentrations than in non-G carriers. These differences, however, were not observed in cohort 2. In cohort 2, G-carriers had lower BMI and waist circumferences than in non-G carriers. The G allele was more frequent among lean than obese patients (RR=1.067, 95%CI=1.053–2.651, p=0.015). An association between BMI and rs4918 polymorphism was observed among patients without diabetes (CC/CG/GG genotypes: p=0.003, G vs. non-G allele: p=0.008) but not in diabetics. In addition, a strong linearity between BMI and the CC/CG/GG genotypes (association value: 4.416, p=0.036) and the frequency of the G allele (7.420, p=0.006) could be identified. In cohort 2, non-obese, non-diabetic G-carriers still had lower BMI and waist circumferences than in non-G carriers. Conclusions The rs4918 minor variant is associated with lower TNFα and adiponectin, higher leptin levels in healthy persons, and more favorable anthropomorphic parameters of obesity in cohort 2. PMID:27487851

NY-ESO-1 Protein Cancer Vaccine With Poly-ICLC and OK-432: Rapid and Strong Induction of NY-ESO-1-specific Immune Responses by Poly-ICLC.

PubMed

Takeoka, Tomohira; Nagase, Hirotsugu; Kurose, Koji; Ohue, Yoshihiro; Yamasaki, Makoto; Takiguchi, Shuji; Sato, Eiichi; Isobe, Midori; Kanazawa, Takayuki; Matsumoto, Mitsunobu; Iwahori, Kota; Kawashima, Atsunari; Morimoto-Okazawa, Akiko; Nishikawa, Hiroyoshi; Oka, Mikio; Pan, Linda; Venhaus, Ralph; Nakayama, Eiichi; Mori, Masaki; Doki, Yuichiro; Wada, Hisashi

2017-03-23

We conducted a clinical trial of a cancer vaccine using NY-ESO-1 protein with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) and/or OK-432 against solid tumors. A total of 15 patients were sequentially enrolled in 4 cohorts. Patients in cohort 1 received NY-ESO-1 protein; cohort 2a received NY-ESO-1 protein+OK-432; cohort 2b received NY-ESO-1 protein+poly-ICLC; cohort 3 received NY-ESO-1 protein+OK-432+poly-ICLC with Montanide ISA-51. The endpoints of this trial were safety, NY-ESO-1 immune responses, and clinical response. Vaccine-related adverse events observed were fever and injection-site reaction (grade 1). Two patients showed stable disease after vaccination. NY-ESO-1 antibodies were observed in 4 patients at the baseline (sero-positive) and augmented in all patients after vaccination. Eleven patients showed a conversion of negative antibody responses at baseline to positive after vaccination (seroconversion). The seroconversions were observed in all 11 sero-negative patients by the fourth immunization; in particular, it was observed by the second immunization in patients with poly-ICLC, and these induced antibody responses were stronger than those in patients immunized without poly-ICLC. The number of NY-ESO-1-specific interferon (IFN)γ-producing T cells was increased in patients immunized with poly-ICLC and/or OK-432, and furthermore, the increase of IFNγ-producing CD8 T cells in patients immunized with poly-ICLC was significantly higher than that in patients without poly-ICLC. Nonspecific activations of T-cell or antigen presenting cells were not observed. Our present study showed that poly-ICLC is a promising adjuvant for cancer vaccines.

Cohort Profile: HAART Observational Medical Evaluation and Research (HOMER) cohort.

PubMed

Patterson, Sophie; Cescon, Angela; Samji, Hasina; Cui, Zishan; Yip, Benita; Lepik, Katherine J; Moore, David; Lima, Viviane D; Nosyk, Bohdan; Harrigan, P Richard; Montaner, Julio S G; Shannon, Kate; Wood, Evan; Hogg, Robert S

2015-02-01

Since 1986, antiretroviral therapy (ART) has been available free of charge to individuals living with HIV in British Columbia (BC), Canada, through the BC Centre of Excellence in HIV/AIDS (BC-CfE) Drug Treatment Program (DTP). The Highly Active Antiretroviral Therapy (HAART) Observational Medical Evaluation and Research (HOMER) cohort was established in 1996 to maintain a prospective record of clinical measurements and medication profiles of a subset of DTP participants initiating HAART in BC. This unique cohort provides a comprehensive data source to investigate mortality, prognostic factors and treatment response among people living with HIV in BC from the inception of HAART. Currently over 5000 individuals are enrolled in the HOMER cohort. Data captured include socio-demographic characteristics (e.g. sex, age, ethnicity, health authority), clinical variables (e.g. CD4 cell count, plasma HIV viral load, AIDS-defining illness, hepatitis C co-infection, mortality) and treatment variables (e.g. HAART regimens, date of treatment initiation, treatment interruptions, adherence data, resistance testing). Research findings from the HOMER cohort have featured in numerous high-impact peer-reviewed journals. The HOMER cohort collaborates with other HIV cohorts on both national and international scales to answer complex HIV-specific research questions, and welcomes input from external investigators regarding potential research proposals or future collaborations. For further information please contact the principal investigator, Dr Robert Hogg (robert_hogg@sfu.ca). © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis.

PubMed

Lalani, Tahaniyat; Chu, Vivian H; Park, Lawrence P; Cecchi, Enrico; Corey, G Ralph; Durante-Mangoni, Emanuele; Fowler, Vance G; Gordon, David; Grossi, Paolo; Hannan, Margaret; Hoen, Bruno; Muñoz, Patricia; Rizk, Hussien; Kanj, Souha S; Selton-Suty, Christine; Sexton, Daniel J; Spelman, Denis; Ravasio, Veronica; Tripodi, Marie Françoise; Wang, Andrew

2013-09-09

There are limited prospective, controlled data evaluating survival in patients receiving early surgery vs medical therapy for prosthetic valve endocarditis (PVE). To determine the in-hospital and 1-year mortality in patients with PVE who undergo valve replacement during index hospitalization compared with patients who receive medical therapy alone, after controlling for survival and treatment selection bias. Participants were enrolled between June 2000 and December 2006 in the International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS), a prospective, multinational, observational cohort of patients with infective endocarditis. Patients hospitalized with definite right- or left-sided PVE were included in the analysis. We evaluated the effect of treatment assignment on mortality, after adjusting for biases using a Cox proportional hazards model that included inverse probability of treatment weighting and surgery as a time-dependent covariate. The cohort was stratified by probability (propensity) for surgery, and outcomes were compared between the treatment groups within each stratum. Valve replacement during index hospitalization (early surgery) vs medical therapy. In-hospital and 1-year mortality. Of the 1025 patients with PVE, 490 patients (47.8%) underwent early surgery and 535 individuals (52.2%) received medical therapy alone. Compared with medical therapy, early surgery was associated with lower in-hospital mortality in the unadjusted analysis and after controlling for treatment selection bias (in-hospital mortality: hazard ratio [HR], 0.44 [95% CI, 0.38-0.52] and lower 1-year mortality: HR, 0.57 [95% CI, 0.49-0.67]). The lower mortality associated with surgery did not persist after adjustment for survivor bias (in-hospital mortality: HR, 0.90 [95% CI, 0.76-1.07] and 1-year mortality: HR, 1.04 [95% CI, 0.89-1.23]). Subgroup analysis indicated a lower in-hospital mortality with early surgery in the highest surgical propensity quintile (21.2% vs 37.5%; P = .03). At 1-year follow-up, the reduced mortality with surgery was observed in the fourth (24.8% vs 42.9%; P = .007) and fifth (27.9% vs 50.0%; P = .007) quintiles of surgical propensity. Prosthetic valve endocarditis remains associated with a high 1-year mortality rate. After adjustment for differences in clinical characteristics and survival bias, early valve replacement was not associated with lower mortality compared with medical therapy in the overall cohort. Further studies are needed to define the effect and timing of surgery in patients with PVE who have indications for surgery.

Serum C-Reactive Protein as a Prognostic Biomarker in Amyotrophic Lateral Sclerosis

PubMed Central

Lizio, Andrea; Maestri, Eleonora; Sansone, Valeria Ada; Mora, Gabriele; Miller, Robert G.; Appel, Stanley H.; Chiò, Adriano

2017-01-01

Importance Various factors have been proposed as possible candidates associated with the prognosis of amyotrophic lateral sclerosis (ALS); however, there is still no consensus on which biomarkers are reliable prognostic factors. C-reactive protein (CRP) is a biomarker of the inflammatory response that shows significant prognostic value for several diseases. Objective To examine the prognostic significance of CRP in ALS. Design, Setting, and Participants Patients’ serum CRP levels were evaluated from January 1, 2009, to June 30, 2015, in a large cohort of patients with ALS observed by an Italian tertiary multidisciplinary center. Results were replicated in an independent cohort obtained from a population-based registry of patients with ALS. A post hoc analysis was performed of the phase 2 trial of NP001 to determine whether stratification by levels of CRP improves differentiation of responders and nonresponders to the drug. Main Outcomes and Measures Serum CRP levels from the first examination were recorded to assess their effect on disease progression and survival. Results A total of 394 patients with ALS (168 women and 226 men; mean [SD] age at diagnosis, 60.18 [13.60] years) were observed in a tertiary multidisciplinary center, and the analysis was replicated in an independent cohort of 116 patients with ALS (50 women and 66 men; mean [SD] age at diagnosis, 67.00 [10.74] years) identified through a regional population-based registry. Serum CRP levels in the 394 patients with ALS correlated with severity of functional impairment, as measured by total score on the ALS Functional Rating Scale–Revised, at first evaluation (r = –0.14818; P = .004), and with patient survival (hazard ratio, 1.129; 95% CI, 1.033-1.234; P = .007). Similar results were found in the independent cohort (hazard ratio, 1.044; 95% CI, 1.016-1.056; P ≤ .001). Moreover, a post hoc analysis of the phase 2 trial of NP001 using the same CRP threshold showed that patients with elevated baseline CRP levels receiving the higher dose of NP001 had significantly less functional impairment after the treatment period compared with patients with normal baseline CRP, regardless of whether patients with normal CRP levels received NP001 or placebo (3.00 [3.62] vs –7.31 [6.23]; P = .04). Conclusions and Relevance These findings suggest that patients with ALS and elevated serum CRP levels progress more rapidly than do those with lower CRP levels and that this elevation may reflect a neuroinflammatory state potentially responsive to the immune regulators such as NP001. PMID:28384752

Do early life cognitive ability and self-regulation skills explain socio-economic inequalities in academic achievement? An effect decomposition analysis in UK and Australian cohorts.

PubMed

Pearce, Anna; Sawyer, Alyssa C P; Chittleborough, Catherine R; Mittinty, Murthy N; Law, Catherine; Lynch, John W

2016-09-01

Socio-economic inequalities in academic achievement emerge early in life and are observed across the globe. Cognitive ability and "non-cognitive" attributes (such as self-regulation) are the focus of many early years' interventions. Despite this, little research has compared the contributions of early cognitive and self-regulation abilities as separate pathways to inequalities in academic achievement. We examined this in two nationally representative cohorts in the UK (Millennium Cohort Study, n = 11,168; 61% original cohort) and Australia (LSAC, n = 3028; 59% original cohort). An effect decomposition method was used to examine the pathways from socio-economic disadvantage (in infancy) to two academic outcomes: 'low' maths and literacy scores (based on bottom quintile) at age 7-9 years. Risk ratios (RRs, and bootstrap 95% confidence intervals) were estimated with binary regression for each pathway of interest: the 'direct effect' of socio-economic disadvantage on academic achievement (not acting through self-regulation and cognitive ability in early childhood), and the 'indirect effects' of socio-economic disadvantage acting via self-regulation and cognitive ability (separately). Analyses were adjusted for baseline and intermediate confounding. Children from less advantaged families were up to twice as likely to be in the lowest quintile of maths and literacy scores. Around two-thirds of this elevated risk was 'direct' and the majority of the remainder was mediated by early cognitive ability and not self-regulation. For example in LSAC: the RR for the direct pathway from socio-economic disadvantage to poor maths scores was 1.46 (95% CI: 1.17-1.79). The indirect effect of socio-economic disadvantage through cognitive ability (RR = 1.13 [1.06-1.22]) was larger than the indirect effect through self-regulation (1.05 [1.01-1.11]). Similar patterns were observed for both outcomes and in both cohorts. Policies to alleviate social inequality (e.g. child poverty reduction) remain important for closing the academic achievement gap. Early interventions to improve cognitive ability (rather than self-regulation) also hold potential for reducing inequalities in children's academic outcomes. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Long-term effect of statins on the risk of new-onset osteoporosis: A nationwide population-based cohort study.

PubMed

Lin, Tsung-Kun; Chou, Pesus; Lin, Ching-Heng; Hung, Yi-Jen; Jong, Gwo-Ping

2018-01-01

Several observational cohort and meta-analytical studies in humans have shown that statin users have a lower risk of fractures or greater bone mineral densities (BMD) than nonusers. However, some studies including randomized clinical trials have the opposite results, particularly in Asian populations. This study investigates the impacts of statins on new-onset osteoporosis in Taiwan. In a nationwide retrospective population-based cohort study, 45,342 subjects aged between 50-90 years having received statin therapy (statin-users) since January 1 2001, and observed through December 31 2013 were selected from the National Health Insurance Research Database of Taiwan. Likewise, 115,594 patients had no statin therapy (statin-non-users) were included as controls in this study. Multivariable Cox proportional hazards analysis for drug exposures was employed to evaluate the association between statin treatment and new-onset of osteoporosis risk. We also used the long-rank test to evaluate the difference of probability of osteoporosis-free survival. During the 13-year follow-up period, 16,146 of all enrolled subjects (10.03%) developed osteoporosis, including 3097 statin-users (6.83%) and 13,049 statin-non-users (11.29%). Overall, statin therapy reduced the risk of new-onset osteoporosis by 48% (adjusted hazard ratio [HR] 0.52; 95% CI 0.50 to 0.54). A dose-response relationship between statin treatment and the risk of new-onset osteoporosis was observed. The adjusted hazard ratios for new-onset osteoporosis were 0.84 (95% CI, 0.78 to 0.90), 0.56 (95% CI, 0.52 to 0.60) and 0.23 (95% CI, 0.21 to 0.25) when cumulative defined daily doses (cDDDs) ranged from 28 to 90, 91 to 365, and more than 365, respectively, relative to nonusers. Otherwise, high-potency statins (rosuvastatin and atorvastatin) and moderate-potency statin (simvastatin) seemed to have a potential protective effect for osteoporosis. In this population-based cohort study, we found that statin use is associated with a decreased risk of osteoporosis in both genders. The osteoprotective effect of statins seemed to be more prominent with a dependency on the cumulative dosage and statin intensity.

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

Recent progresses in outcome-dependent sampling with failure time data.

PubMed

Ding, Jieli; Lu, Tsui-Shan; Cai, Jianwen; Zhou, Haibo

2017-01-01

An outcome-dependent sampling (ODS) design is a retrospective sampling scheme where one observes the primary exposure variables with a probability that depends on the observed value of the outcome variable. When the outcome of interest is failure time, the observed data are often censored. By allowing the selection of the supplemental samples depends on whether the event of interest happens or not and oversampling subjects from the most informative regions, ODS design for the time-to-event data can reduce the cost of the study and improve the efficiency. We review recent progresses and advances in research on ODS designs with failure time data. This includes researches on ODS related designs like case-cohort design, generalized case-cohort design, stratified case-cohort design, general failure-time ODS design, length-biased sampling design and interval sampling design.

Recent progresses in outcome-dependent sampling with failure time data

PubMed Central

Ding, Jieli; Lu, Tsui-Shan; Cai, Jianwen; Zhou, Haibo

2016-01-01

An outcome-dependent sampling (ODS) design is a retrospective sampling scheme where one observes the primary exposure variables with a probability that depends on the observed value of the outcome variable. When the outcome of interest is failure time, the observed data are often censored. By allowing the selection of the supplemental samples depends on whether the event of interest happens or not and oversampling subjects from the most informative regions, ODS design for the time-to-event data can reduce the cost of the study and improve the efficiency. We review recent progresses and advances in research on ODS designs with failure time data. This includes researches on ODS related designs like case–cohort design, generalized case–cohort design, stratified case–cohort design, general failure-time ODS design, length-biased sampling design and interval sampling design. PMID:26759313

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.

Do outcomes after kidney transplantation differ for black patients in England versus New York State? A comparative, population-cohort analysis.

PubMed

Tahir, Sanna; Gillott, Holly; Jackson-Spence, Francesca; Nath, Jay; Mytton, Jemma; Evison, Felicity; Sharif, Adnan

2017-05-09

Inferior outcomes for black kidney transplant recipients in the USA may not be generalisable elsewhere. In this population cohort analysis, we compared outcomes for black kidney transplant patients in England versus New York State. Retrospective, comparative, population cohort study utilising administrative data registries. English data were derived from Hospital Episode Statistics, while New York State data were derived from Statewide Planning and Research Cooperative System. All adults receiving their first kidney-alone allograft between 2003 and 2013 were eligible for inclusion. The primary outcome measure was mortality post kidney transplantation (including inhospital death, 30-day mortality and 1-year mortality). Secondary outcome measures included postoperative admission length of stay, risk of rehospitalisation, development of cardiac events, stroke, cancer or fracture and finally transplant rejection/failure. Cox proportional hazards regression was used to investigate relationship between ethnicity, country and outcome. Black patients comprised 6.5% of the English cohort (n=1215/18 493) and 23.0% of the New York State cohort (n=2660/11 602). Compared with New York State, black kidney transplant recipients in England were more likely younger, male, living-donor kidney recipients and had dissimilar medical comorbidities. Inpatient mortality was not statistically different, but death within 30 days, 1 year or kidney transplant rejection/failure was lower among black patients in England versus black patients in New York State. In adjusted regression analysis, with black ethnicity the reference group, white patients had reduced risk for 30-day mortality (OR 0.62 (95% CI 0.44 to 0.86)) and 1-year mortality (OR 0.79 (95% CI 0.63 to 0.99)) in New York State but no difference was observed in England. Compared with England, black kidney transplant patients in New York State had increased HR for kidney transplant rejection rejection/failure by median follow-up (HR 2.15, 95% CI 1.91 to 2.43). Outcomes after kidney transplantation for black patients may not be translatable between countries. © 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.

Doctors or mid-level providers for abortion.

PubMed

Barnard, Sharmani; Kim, Caron; Park, Min Hae; Ngo, Thoai D

2015-07-27

The World Health Organization recommends that abortion can be provided at the lowest level of the healthcare system. Training mid-level providers, such as midwives, nurses and other non-physician providers, to conduct first trimester aspiration abortions and manage medical abortions has been proposed as a way to increase women's access to safe abortion procedures. To assess the safety and effectiveness of abortion procedures administered by mid-level providers compared to doctors. We searched the CENTRAL Issue 7, MEDLINE and POPLINE databases for comparative studies of doctor and mid-level providers of abortion services. We searched for studies published in any language from January 1980 until 15 August 2014. Randomised controlled trials (RCTs) (clustered or not clustered), prospective cohort studies or observational studies that compared the safety or effectiveness (or both) of any type of first trimester abortion procedure, administered by any type of mid-level provider or doctors, were eligible for inclusion in the review. Two independent review authors screened abstracts for eligibility and double-extracted data from the included studies using a pre-tested form. We meta-analysed primary outcome data using both fixed-effect and random-effects models to obtain pooled risk ratios (RR) with 95% confidence intervals (CIs). We carried out separate analyses by study design (RCT or cohort) and type of abortion procedure (medical versus surgical). Eight studies involving 22,018 participants met our eligibility criteria. Five studies (n = 18,962) assessed the safety and effectiveness of surgical abortion procedures administered by mid-level providers compared to doctors. Three studies (n = 3056) assessed the safety and effectiveness of medical abortion procedures. The surgical abortion studies (one RCT and four cohort studies) were carried out in the United States, India, South Africa and Vietnam. The medical abortion studies (two RCTs and one cohort study) were carried out in India, Sweden and Nepal. The studies included women with gestational ages up to 14 weeks for surgical abortion and nine weeks for medical abortion.Risk of selection bias was considered to be low in the three RCTs, unclear in four observational studies and high in one observational study. Concealment bias was considered to be low in the three RCTs and high in all five observational studies. Although none of the eight studies performed blinding of the participants to the provider type, we considered the performance bias to be low as this is part of the intervention. Detection bias was considered to be high in all eight studies as none of the eight studies preformed blinding of the outcome assessment. Attrition bias was low in seven studies and high in one, with over 20% attrition. We considered six studies to have unclear risk of selective reporting bias as their protocols had not been published. The remaining two studies had published their protocols. Few other sources of bias were found.Based on an analysis of three cohort studies, the risk of surgical abortion failure was significantly higher when provided by mid-level providers than when procedures were administered by doctors (RR 2.25, 95% CI 1.38 to 3.68), however the quality of evidence for this outcome was deemed to be very low. For surgical abortion procedures, we found no significant differences in the risk of complications between mid-level providers and doctors (RR 0.99, 95% CI 0.17 to 5.70 from RCTs; RR 1.38, 95% CI 0.70 to 2.72 from observational studies). When we combined the data for failure and complications for surgical abortion we found no significant differences between mid-level providers and doctors in both the observational study analysis (RR 1.36, 95% CI 0.86 to 2.14) and the RCT analysis (RR 3.07, 95% CI 0.16 to 59.08). The quality of evidence of the outcome for RCT studies was considered to be low and for observational studies very low. For medical abortion procedures the risk of failure was not different for mid-level providers or doctors (RR 0.81, 95% CI 0.48 to 1.36 from RCTs; RR 1.09, 95% CI 0.63 to 1.88 from observational studies). The quality of evidence of this outcome for the RCT analysis was considered to be high, although the quality of evidence of the observational studies was considered to be very low. There were no complications reported in the three medical abortion studies. There was no statistically significant difference in the risk of failure for medical abortions performed by mid-level providers compared with doctors. Observational data indicate that there may be a higher risk of abortion failure for surgical abortion procedures administered by mid-level providers, but the number of studies is small and more robust data from controlled trials are needed. There were no statistically significant differences in the risk of complications for first trimester surgical abortions performed by mid-level providers compared with doctors.

[Active tuberculosis in a cohort of HIV-infected inmates in a prison in Mexico City: clinical and epidemiological characteristics].

PubMed

Hernández-León, Christian; Badial-Hernández, Florentino; Ponce-de-León, Alfredo; Sierra-Madero, Juan G; Martínez-Gamboa, Areli; Crabtree-Ramírez, Brenda; Bautista-Arredondo, Sergio; González-Aguirre, Adrián; Guerrero-Almeida, María de Lourdes; del Valle, J Miriam Bobadilla; González-Rodríguez, Andrea; Sifuentes-Osornio, José

2012-01-01

To determine the clinical and epidemiological characteristics of prison inmates with active tuberculosis in HIV-positive prison populations. We conducted a cohort study in HIV-infected subjects in a prison in Mexico City, with the aim of determining clinical and epidemiological characteristics of cases with active TB. We detected 172 HIV infected inmates and TB in 28 of them (16.3%) - 21 (12.2) with pulmonary TB--with an incidence rate of 7.7/100 persons/year for active TB and 4.7/100 persons/year for pulmonary TB. No drug resistance was found. Two clusters (4 and 2 subjects) were observed after RFLP-typing of 18 isolates, with a transmission rate of 11% by molecular and clinical analysis. The prevalence of active TB was found to be a thousand times greater than in the general population. Evidence of transmission inside the prison was also found.

Advancing epilepsy treatment through personalized genetic zebrafish models.

PubMed

Griffin, A; Krasniak, C; Baraban, S C

2016-01-01

With an increase in the number of disease causing genetic mutations identified from epilepsy cohorts, zebrafish are proving to be an attractive vertebrate model for functional analysis of these allele variants. Not only do zebrafish have conserved gene functions, but larvae harboring mutations in identified human epileptic genes show spontaneous seizure activity and mimic the convulsive behavioral movements observed in humans. With zebrafish being compatible with medium to high-throughput screening, they are also proving to be a unique and powerful system for early preclinical drug screening, including novel target identification, pharmacology, and toxicology. Additionally, with recent advances in genomic engineering technologies, it is now possible to study the precise pathophysiology of patient-specific gene mutations in zebrafish. The following sections highlight how the unique attributes of zebrafish, in combination with genetic modifications, are continuing to transform our understanding of epilepsy and help identify personalized therapeutics for specific patient cohorts. © 2016 Elsevier B.V. All rights reserved.

Mortality of Talc Miners and Millers From Val Chisone, Northern Italy: An Updated Cohort Study.

PubMed

Pira, Enrico; Coggiola, Maurizio; Ciocan, Catalina; Romano, Canzio; La Vecchia, Carlo; Pelucchi, Claudio; Boffetta, Paolo

2017-07-01

The aim of this study was to update the analysis of mortality of a cohort of talc miners and millers in Northern Italy. We analyzed the mortality during 1946 to 2013 of 1722 male workers in an asbestos-free talc mine (1166 miners and 556 millers) employed during 1946 to 1995. The overall standardized mortality ratio (SMR) was 1.24 [95% confidence interval (95% CI) 1.17 to 1.32]; no deaths were observed from pleural cancer; mortality from lung cancer was not increased. Mortality from pneumoconiosis was increased (SMR 26.62; 95% CI 20.71 to 33.69), in particular among miners, and was associated with duration of employment and time since first employment. We confirmed the lack of association between exposure to asbestos-free talc, lung cancer, and mesothelioma. Increased mortality from pneumoconiosis among miners is attributable to past exposure to silica.

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.

Association Between Cardiovascular Risk Factors and Carpal Tunnel Syndrome in Pooled Occupational Cohorts.

PubMed

Hegmann, Kurt T; Thiese, Matthew Steven; Kapellusch, Jay; Merryweather, Andrew S; Bao, Stephen; Silverstein, Barbara; Wood, Eric M; Kendall, Richard; Wertsch, Jacqueline; Foster, James; Garg, Arun; Drury, David L

2016-01-01

The aim of the study was to ascertain if cardiovascular (CVD) risk factors are carpal tunnel syndrome (CTS) risk factors. Analysis of pooled baseline data from two large prospective cohort studies (n = 1824) assessed the relationships between a modified Framingham Heart Study CVD risk score both CTS and abnormal nerve conduction study prevalence. Quantified job exposures, personal and psychosocial confounders were statistically controlled. Odds ratio and 95% confidence intervals were calculated for individual risk scores. There was a strong relationship between CVD risk score and both CTS and abnormal nerve conduction study after adjustment for confounders, with odds ratios as high as 4.16 and 7.35, respectively. Dose responses were also observed. In this workplace population, there is a strong association between CVD risk scores and both CTS and abnormal nerve conduction study that persisted after controlling for confounders. These data suggest a potentially modifiable disease mechanism.

Health Status of Women in the Armed Forces

DTIC Science & Technology

1991-12-01

1984, howeper, women’s rates for acute upper respiratory infection, diarrheal disease, ribella, and infectious mononucleosis had declined to such an...were observed for induced abortions and acute upper respiratory infection for the 1973-77 cohort; alcohol abuse and complications of pregnancy for the...1978-82 cohort; and complications of pregnancy and transient situational disturbances for the 1983-87 cohort. The most vulnerable time for the

Associations between ASA Physical Status and postoperative mortality at 48 h: a contemporary dataset analysis compared to a historical cohort.

PubMed

Hopkins, Thomas J; Raghunathan, Karthik; Barbeito, Atilio; Cooter, Mary; Stafford-Smith, Mark; Schroeder, Rebecca; Grichnik, Katherine; Gilbert, Richard; Aronson, Solomon

2016-01-01

In this study, we examined the association between American Society of Anesthesiologists Physical Status (ASA PS) designation and 48-h mortality for both elective and emergent procedures in a large contemporary dataset (patient encounters between 2009 and 2014) and compared this association with data from a landmark study published by Vacanti et al. in 1970. Patient history, hospital characteristics, anesthetic approach, surgical procedure, efficiency and quality indicators, and patient outcomes were prospectively collected for 732,704 consecutive patient encounters between January 1, 2009, and December 31, 2014, at 233 anesthetizing locations across 19 facilities in two US states and stored in the Quantum™ Clinical Navigation System (QCNS) database. The outcome (death within 48 h of procedure) was tabulated against ASA PS designations separately for patients with and without "E" status labels. To maintain consistency with the historical cohort from the landmark study performed by Vacanti et al. on adult men at US naval hospitals in 1970, we then created a comparison cohort in the contemporary dataset that consisted of 242,103 adult male patients (with/without E designations) undergoing elective and emergent procedures. Differences in the relationship between ASA PS and 48-h mortality in the historical and contemporary cohorts were assessed for patients undergoing elective and emergent procedures. As reported nearly five decades ago, we found a significant trend toward increased mortality with increasing ASA PS for patients undergoing both elective and emergent procedures in a large contemporary cohort ( p  < 0.0001). Additionally, the overall mortality rate at 48 h was significantly higher among patients undergoing emergent compared to elective procedures in the large contemporary cohort (1.27 versus 0.03 %, p  < 0.0001). In the comparative analysis with the historical cohort that focused on adult males, we found the overall 48-h mortality rate was significantly lower among patients undergoing elective procedures in the contemporary cohort (0.05 % now versus 0.24 % in 1970, p  < 0.0001) but not significantly lower among those undergoing emergent procedures (1.88 % now versus 1.22 % in 1970, p  < 0.0001). The association between increasing ASA PS designation (1-5) and mortality within 48 h of surgery is significant for patients undergoing both elective and emergent procedures in a contemporary dataset consisting of over 700,000 patient encounters. Emergency surgery was associated with a higher risk of patient death within 48 h of surgery in this contemporary dataset. These data trends are similar to those observed nearly five decades ago in a landmark study evaluating the association between ASA PS and 48-h surgical mortality on adult men at US naval hospitals. When a comparison cohort was created from the contemporary dataset and compared to this landmark historical cohort, the absolute 48-h mortality rate was significantly lower in the contemporary cohort for elective procedures but not significantly lower for emergency procedures. The underlying implications of these findings remain to be determined.

Linking Investigations in Trauma and Emergency Services (LITES)

DTIC Science & Technology

2017-10-01

observational cohort that will have a limited data set from trauma registry data and electronic health records. Specific Aim one is to characterize the...epidemiology of moderate and severe physical injury in the U.S. and across the LITES network and investigate regional variations of presenting...observational cohort that will have a limited data set from trauma registry data and electronic health records. Specific Aim one is to characterize the

Implementation and Operational Research: CD4 Count Monitoring Frequency and Risk of CD4 Count Dropping Below 200 Cells Per Cubic Millimeter Among Stable HIV-Infected Patients in New York City, 2007-2013.

PubMed

Myers, Julie E; Xia, Qiang; Torian, Lucia V; Irvine, Mary; Harriman, Graham; Sepkowitz, Kent A; Shepard, Colin W

2016-03-01

The evidence has begun to mount for diminishing the frequency of CD4 count testing. To determine whether these observations were applicable to an urban US population, we used New York City (NYC) surveillance data to explore CD4 testing among stable patients in NYC, 2007-2013. We constructed a population-based retrospective open cohort analysis of NYC HIV surveillance data. HIV+ patients aged ≥ 13 years with stable viral suppression (≥ 1 viral load the previous year; all <400 copies per milliliter) and immune status (≥ 1 CD4 the previous year; all ≥ 200 cells per cubic millimeter) entered the cohort the following year beginning January 1, 2007. Each subsequent year, eligible patients not previously included entered the cohort on January 1. Outcomes were annual frequency of CD4 monitoring and probability of maintaining CD4 ≥ 200 cells per cubic millimeter. A multivariable Cox model identified factors associated with maintaining CD4 ≥ 200 cells per cubic millimeter. During 1.9 years of observation (median), 62,039 patients entered the cohort. The mean annual number of CD4 measurements among stable patients was 2.8 and varied little by year or characteristic. Two years after entering, 93.4% and 97.8% of those with initial CD4 350-499 and CD4 ≥ 500 cells per cubic millimeter, respectively, maintained CD4 ≥ 200 cells per cubic millimeter. Compared to those with initial CD4 ≥ 500 cells per cubic millimeter, those with CD4 200-349 cells per cubic millimeter and CD4 350-499 cells per cubic millimeter were more likely to have a CD4 <200 cells per cubic millimeter, controlling for sex, race, age, HIV risk group, and diagnosis year. In a population-based US cohort with well-controlled HIV, the probability of maintaining CD4 ≥ 200 cells per cubic millimeter for ≥ 2 years was >90% among those with initial CD4 ≥ 350 cells per cubic millimeter, suggesting that limited CD4 monitoring in these patients is appropriate.

The association of statin therapy with the risk of recurrent venous thrombosis.

PubMed

Smith, N L; Harrington, L B; Blondon, M; Wiggins, K L; Floyd, J S; Sitlani, C M; McKnight, B; Larson, E B; Rosendaal, F R; Heckbert, S R; Psaty, B M

2016-07-01

Essentials A lowered risk of recurrent venous thrombosis (VT) with statin treatment is controversial. Among observational inception cohort of 2,798 adults with incident VT, 457 had recurrent VT. Time-to-event models with time-varying statin use and adjustment for potential confounders was used for analysis. Compared to nonuse, current statin use was associated with 26% lower risk of recurrent VT. Click to hear Prof. Büller's perspective on Anticoagulant Therapy in the Treatment of Venous Thromboembolism Background Meta-analyses of randomized controlled trials suggest that treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) lowers the risk of incident venous thrombosis (VT), particularly among those without prevalent clinical cardiovascular disease (CVD). Whether this is true for the prevention of recurrent VT is debated. We used an observational inception cohort to estimate the association of current statin use with the risk of recurrent VT. Methods and Results The study setting was a large healthcare organization with detailed medical record and pharmacy information at cohort entry and throughout follow-up. We followed 2798 subjects 18-89 years of age who experienced a validated incident VT between January 1, 2002, and December 31, 2010, for a first recurrent VT, validated by medical record review. During follow-up, 457 (16%) developed a first recurrent VT. In time-to-event models incorporating time-varying statin use and adjusting for potential confounders, current statin use was associated with a 26% lower risk of recurrent VT: hazard ratio 0.74, 95% confidence interval 0.59-0.94. Among cohort members free of CVD (n = 2134), current statin use was also associated with a lower risk (38%) of recurrent VT: hazard ratio 0.62, 95% confidence interval 0.45-0.85. We found similar results when restricting to new users of statins and in subgroups of different statin types and doses. Conclusions In a population-based cohort of subjects who had experienced an incident VT, statin use, compared with nonuse, was associated with a clinically relevant lower risk of recurrent VT. These findings suggest a potential secondary benefit of statins among patients who have experienced an incident VT. © 2016 International Society on Thrombosis and Haemostasis.

Changing trends in reproductive/lifestyle factors in UK women: descriptive study within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

PubMed Central

Gentry-Maharaj, Aleksandra; Glazer, Clara; Burnell, Matthew; Ryan, Andy; Berry, Hannah; Kalsi, Jatinderpal; Woolas, Robert; Skates, Steve J; Campbell, Stuart; Jacobs, Ian

2017-01-01

Objective There has been considerable interest in the impact of reproductive factors on health but there are little data on how these have varied over time. We explore trends in reproductive/lifestyle factors of postmenopausal British women by analysing self-reported data from participants of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Design Prospective birth cohort analysis. Setting Population cohort invited between 2001 and 2005 from age-sex registers of 27 Primary Care Trusts in England, Wales and Northern Ireland and recruited through 13 National Health Service Trusts. Participants 202 638 postmenopausal women aged 50–74 years at randomisation to UKCTOCS between April 2001 and October 2005. Interventions Women were stratified into the following six birth cohorts (1925–1929, 1930–1934, 1935–1939, 1940–1944, 1945–1949, 1950–1955) based on year of birth. Self-reported data on reproductive factors provided at recruitment were explored using tabular and graphical summaries to examine for differences between the birth cohorts. Outcome measures Trends in mean age at menarche and menopause, use of oral contraceptives, change in family size, infertility treatments, tubal ligation and hysterectomy rates. Results Women born between 1935 and 1955 made up 86% of the cohort. Median age at menarche decreased from 13.4 for women born between 1925 and 1929 to 12.8 for women born between 1950 and 1955. Increased use of the oral contraceptives, infertility treatments and smaller family size was observed in the younger birth cohorts. Tubal ligation rates increased for those born between 1925 and 1945, but this increase did not persist in subsequent cohorts. Hysterectomy rates (17–20%) did not change over time. Conclusions The trends seen in this large cohort are likely to reflect the reproductive history of the UK female postmenopausal population of similar age. Since these are risk factors for hormone-related cancers, these trends are important in understanding the changing incidence of these cancers. Trial registration number International Standard Randomised Controlled Trial Number: 22488978. PMID:28264823

Diagnostic Accuracy of 64Copper Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography for Primary Lymph Node Staging of Intermediate- to High-risk Prostate Cancer: Our Preliminary Experience.

PubMed

Cantiello, Francesco; Gangemi, Vincenzo; Cascini, Giuseppe Lucio; Calabria, Ferdinando; Moschini, Marco; Ferro, Matteo; Musi, Gennaro; Butticè, Salvatore; Salonia, Andrea; Briganti, Alberto; Damiano, Rocco

2017-08-01

To assess the diagnostic accuracy of 64 Copper prostate-specific membrane antigen ( 64 Cu-PSMA) positron emission tomography/computed tomography (PET/CT) in the primary lymph node (LN) staging of a selected cohort of intermediate- to high-risk prostate cancer (PCa) patients. An observational prospective study was performed in 23 patients with intermediate- to high-risk PCa, who underwent 64 Cu-PSMA PET/CT for local and lymph nodal staging before laparoscopic radical prostatectomy with an extended pelvic LN dissection. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for LN status of 64 Cu-PSMA PET/CT were calculated using the final pathological findings as reference. Furthermore, we evaluated the correlation of intraprostatic tumor extent and grading with 64 Cu-PSMA intraprostatic distribution. Pathological analysis of LN involvement in 413 LNs harvested from our study cohort identified a total of 22 LN metastases in 8 (5%) of the 23 (35%) PCa patients. Imaging-based LN staging in a per-patient analysis showed that 64 Cu-PSMA PET/CT was positive in 7 of 8 LN-positive patients (22%) with a sensitivity of 87.5%, specificity of 100%, PPV of 100%, and NPV of 93.7%, considering the maximum standardized uptake value (SUV max ) at 4 hours as our reference. Receiver operating characteristic curve was characterized by an area under the curve of 0.938. A significant positive association was observed between SUV max at 4 hours with Gleason score, index, and cumulative tumor volume. In our intermediate- to high-risk PCa patients study cohort, we showed the high diagnostic accuracy of 64 Cu-PSMA PET/CT for primary LN staging before radical prostatectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

A comparison of programmable and nonprogrammable compression devices for treatment of lymphoedema using an administrative health outcomes dataset.

PubMed

Karaca-Mandic, P; Hirsch, A T; Rockson, S G; Ridner, S H

2017-12-01

Patients with lymphoedema experience lifelong swelling and recurrent cellulitis despite use of complete decongestive therapy. Pneumatic compression devices (PCDs), including nonprogrammable and programmable devices that meet individual patient needs, support long-term self-care in the home. Patients with either a nonprogrammable device (NP-PCD) or a dynamic pressure programmable device [P-PCD; Flexitouch ® (Tactile Medical, Minneapolis, MN, U.S.A.)] were evaluated to compare associated clinical and health utilization outcomes pre-/postdevice acquisition. Retrospective analysis of deidentified administrative claims from 2007 through 2013 of a large U.S. insurer. Outcome variables included rates of lymphoedema-related cellulitis, manual therapy use, outpatient services and inpatient hospitalizations. Multivariate regression analysis was performed to (i) compare outcomes for the 12 months pre- and postdevice acquisition and (ii) compare these two device types for their treatment-associated benefits. The sample consisted of 1013 NP-PCD and 718 P-PCD recipients. Compared with the NP-PCD group, P-PCD patients' baseline cellulitis rate was higher, whereas their postdevice cellulitis rate was lower. In the cancer cohort, the NP-PCD group had a 53% reduction in episodes of cellulitis (from 17·9% to 8·5%), compared with a greater 79% reduction in the P-PCD group (from 23·7% to 5·0%) (P < 0·001). In the noncancer cohort, the P-PCD group also experienced a larger 76% decline (from 31·0% to 7·4%) vs. 54% decline (from 22·9% to 10·6%) in cellulitis rates (P = 0·003). Outpatient service use reduced in both device groups, with greater reductions observed in the P-PCD group. Both device groups experienced reductions in manual therapy use. Inpatient hospitalizations were largely stable with reductions observed only in the noncancer cohort of the P-PCD group. P-PCD receipt was associated with superior lymphoedema-related health outcomes and reductions in cellulitis. © 2017 British Association of Dermatologists.

Timing of probiotic milk consumption during pregnancy and effects on the incidence of preeclampsia and preterm delivery: a prospective observational cohort study in Norway

PubMed Central

Nordqvist, Mahsa; Jacobsson, Bo; Brantsæter, Anne-Lise; Myhre, Ronny; Nilsson, Staffan; Sengpiel, Verena

2018-01-01

Objectives To investigate whether the timing of probiotic milk intake before, during early or late pregnancy influences associations with preeclampsia and preterm delivery. Design Population based prospective cohort study. Setting Norway, between 1999 and 2008. Participants 70 149 singleton pregnancies resulting in live-born babies from the Norwegian Mother and Child Cohort Study (no chronic disease, answered questionnaires, no placenta previa/cerclage/serious malformation of fetus, first enrolment pregnancy). Only nulliparous women (n=37 050) were included in the preeclampsia analysis. Both iatrogenic and spontaneous preterm delivery (between gestational weeks 22+0 and 36+6) with spontaneous term controls (between gestational weeks 39+0 and 40+6) were included in the preterm delivery analysis resulting in 34 458 cases. Main outcome measures Adjusted OR for preeclampsia and preterm delivery according to consumption of probiotic milk at three different time periods (before pregnancy, during early and late pregnancy). Results Probiotic milk intake in late pregnancy (but not before or in early pregnancy) was significantly associated with lower preeclampsia risk (adjusted OR: 0.80 (95% CI 0.68 to 0.94) p-value: 0.007). Probiotic intake during early (but not before or during late pregnancy) was significantly associated with lower risk of preterm delivery (adjusted OR: 0.79 (0.64 to 0.97) p-value: 0.03). Conclusions In this observational study, we found an association between timing of probiotic milk consumption during pregnancy and the incidence of the adverse pregnancy outcomes preeclampsia and preterm delivery. If future randomised controlled trials could establish a causal association between probiotics consumption and reduced risk of preeclampsia and preterm delivery, recommending probiotics would be a promising public health measure to reduce these adverse pregnancy outcomes. PMID:29362253

Association between osteoarthritis and cardiovascular disease: Systematic review and meta-analysis.

PubMed

Hall, Andrew J; Stubbs, Brendon; Mamas, Mamas A; Myint, Phyo K; Smith, Toby O

2016-06-01

To examine for a possible relationship between osteoarthritis and cardiovascular disease. A systematic review and meta-analysis. Published and unpublished literature from: MEDLINE, EMBASE, CINAHL, the Cochrane Library, OpenGrey and clinical trial registers. Search to 22 November 2014. Cohort, case-control, randomised and non-randomised controlled trial papers reporting the prevalence of cardiovascular disease in osteoarthritis were included. Fifteen studies with 32,278,744 individuals were eligible. Pooled prevalence for overall cardiovascular disease pathology in people with osteoarthritis was 38.4% (95% confidence interval (CI): 37.2% to 39.6%). Individuals with osteoarthritis were almost three times as likely to have heart failure (relative risk (RR): 2.80; 95% CI: 2.25 to 3.49) or ischaemic heart disease (RR: 1.78; 95% CI: 1.18 to 2.69) compared with matched non-osteoarthritis cohorts. No significant difference was detected between the two groups for the risk of experiencing myocardial infarction or stroke. There was a three-fold decrease in the risk of experiencing a transient ischaemic attack in the osteoarthritis cohort compared with the non-osteoarthritis group. Prevalence of cardiovascular disease in patients with osteoarthritis is significant. There was an observed increased risk of incident heart failure and ischaemic heart disease in people with osteoarthritis compared with matched controls. However, the relationship between osteoarthritis and cardiovascular disease is not straightforward and there is a need to better understand the potential common pathways linking pathophysiological mechanisms. © The European Society of Cardiology 2015.

Plasma proteome analysis in patients with pulmonary arterial hypertension: an observational cohort study.

PubMed

Rhodes, Christopher J; Wharton, John; Ghataorhe, Pavandeep; Watson, Geoffrey; Girerd, Barbara; Howard, Luke S; Gibbs, J Simon R; Condliffe, Robin; Elliot, Charles A; Kiely, David G; Simonneau, Gerald; Montani, David; Sitbon, Olivier; Gall, Henning; Schermuly, Ralph T; Ghofrani, H Ardeschir; Lawrie, Allan; Humbert, Marc; Wilkins, Martin R

2017-09-01

Idiopathic and heritable pulmonary arterial hypertension form a rare but molecularly heterogeneous disease group. We aimed to measure and validate differences in plasma concentrations of proteins that are associated with survival in patients with idiopathic or heritable pulmonary arterial hypertension to improve risk stratification. In this observational cohort study, we enrolled patients with idiopathic or heritable pulmonary arterial hypertension from London (UK; cohorts 1 and 2), Giessen (Germany; cohort 3), and Paris (France; cohort 4). Blood samples were collected at routine clinical appointment visits, clinical data were collected within 30 days of blood sampling, and biochemical data were collected within 7 days of blood sampling. We used an aptamer-based assay of 1129 plasma proteins, and patient clinical details were concealed to the technicians. We identified a panel of prognostic proteins, confirmed with alternative targeted assays, which we evaluated against the established prognostic risk equation for pulmonary arterial hypertension derived from the REVEAL registry. All-cause mortality was the primary endpoint. 20 proteins differentiated survivors and non-survivors in 143 consecutive patients with idiopathic or heritable pulmonary arterial hypertension with 2 years' follow-up (cohort 1) and in a further 75 patients with 2·5 years' follow-up (cohort 2). Nine proteins were both prognostic independent of plasma NT-proBNP concentrations and confirmed by targeted assays. The functions of these proteins relate to myocardial stress, inflammation, pulmonary vascular cellular dysfunction and structural dysregulation, iron status, and coagulation. A cutoff-based score using the panel of nine proteins provided prognostic information independent of the REVEAL equation, improving the C statistic from area under the curve 0·83 (for REVEAL risk score, 95% CI 0·77-0·89; p<0·0001) to 0·91 (for panel and REVEAL 0·87-0·96; p<0·0001) and improving reclassification indices without detriment to calibration. Poor survival was preceded by an adverse change in panel score in paired samples from 43 incident patients with pulmonary arterial hypertension in cohort 3 (p=0·0133). The protein panel was validated in 93 patients with idiopathic or heritable pulmonary arterial hypertension in cohort 4, with 4·4 years' follow-up and improved risk estimates, providing complementary information to the clinical risk equation. A combination of nine circulating proteins identifies patients with pulmonary arterial hypertension with a high risk of mortality, independent of existing clinical assessments, and might have a use in clinical management and the evaluation of new therapies. National Institute for Health Research, Wellcome Trust, British Heart Foundation, Assistance Publique-Hôpitaux de Paris, Inserm, Université Paris-Sud, and Agence Nationale de la Recherche. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licence. Published by Elsevier Ltd.. All rights reserved.

[Mortality of psychiatric patients. A retrospective cohort study of in-patients at the Psychiatric Hospital of Reggio Emilia].

PubMed

Ballone, E; Contini, G

1992-03-01

The authors report the results of historical cohort study in long-term patients of psychiatric hospitals in Reggio Emilia. The cohort was formed by 790 patients hospitalized before 1978, and has been followed-up until 31/12/'89. The results of the study are: 269 subjects deceased (34%); 117 discharges (14.8%) and 411 (52.1%) still in hospital on 1/1/'90. An excess mortality was observed in the cohort. Mortality appears to be particularly high among young patient and females.

Intergenerational Mobility in the Post-1965 Immigration Era: Estimates By An Immigrant Generation Cohort Method

PubMed Central

PARK, JULIE; MYERS, DOWELL

2010-01-01

The new second generation of the post-1965 immigration era is observed as children with their parents in 1980 and again as adults 25 years later. Intergenerational mobility is assessed for both men and women in four major racial/ethnic groups, both in regard to children’s status attainment relative to parents and with regard to the rising societal standards proxied by native-born non-Hispanic whites. A profile of intergenerational mobility is prepared using multiple indicators of status attainment: high school and college completion, upper white-collar occupation, poverty, and homeownership. The immigrant generation cohort method we introduce accounts for four distinct temporal dimensions of immigrant progress, clarifying inconsistencies in the literature and highlighting differences in mobility between racial/ethnic groups and with respect to different outcome measures. The immigrant generation cohort method consistently finds greater intergenerational mobility than suggested by alternative approaches. Our analysis also shows that the intergenerational progress of women is greater than that of men and provides a more complete record of immigrant mobility overall. Findings for individual racial/ethnic groups accord with some expectations in the literature and contradict others. PMID:20608102

Identifying and Investigating Unexpected Response to Treatment: A Diabetes Case Study.

PubMed

Ozery-Flato, Michal; Ein-Dor, Liat; Parush-Shear-Yashuv, Naama; Aharonov, Ranit; Neuvirth, Hani; Kohn, Martin S; Hu, Jianying

2016-09-01

The availability of electronic health records creates fertile ground for developing computational models of various medical conditions. We present a new approach for detecting and analyzing patients with unexpected responses to treatment, building on machine learning and statistical methodology. Given a specific patient, we compute a statistical score for the deviation of the patient's response from responses observed in other patients having similar characteristics and medication regimens. These scores are used to define cohorts of patients showing deviant responses. Statistical tests are then applied to identify clinical features that correlate with these cohorts. We implement this methodology in a tool that is designed to assist researchers in the pharmaceutical field to uncover new features associated with reduced response to a treatment. It can also aid physicians by flagging patients who are not responding to treatment as expected and hence deserve more attention. The tool provides comprehensive visualizations of the analysis results and the supporting data, both at the cohort level and at the level of individual patients. We demonstrate the utility of our methodology and tool in a population of type II diabetic patients, treated with antidiabetic drugs, and monitored by the HbA1C test.

The use of antidepressants and the risk of haemorrhagic stroke: a nested case control study

PubMed Central

Douglas, Ian; Smeeth, Liam; Irvine, David

2011-01-01

AIM To investigate whether selective serotonin re-uptake inhibitor (SSRI) use is associated with an increased risk of haemorrhagic stroke in a cohort of antidepressant users. METHODS We conducted a case control study, nested within a cohort of antidepressant users in the United Kingdom General Practice Research Database. A cohort of 365 195 patients prescribed either an SSRI or tricyclic antidepressant between 1992 and 2006 was identified. Three hundred and fifty-seven cases of haemorrhagic stroke were observed and 1631 control patients without haemorrhagic stroke were selected. RESULTS The primary analysis showed no evidence of an association between current SSRI or TCA use and haemorrhagic stroke. Current use of an SSRI compared with no use at the time of haemorrhagic stroke was associated with an adjusted odds ratio of 1.11 (95% confidence interval (CI) 0.82, 1.50). For current tricyclic use the equivalent odds ratio was 0.73 (0.52, 1.02). There was no evidence that prior cerebrovascular events modified the effect of either SSRIs or TCAs. CONCLUSIONS We found no evidence that SSRIs are associated with an increased risk of haemorrhagic stroke, regardless of prior history of cerebrovascular events. PMID:21143507

Serum profiles of PCDDs and PCDFs, in individuals near the Escambia Wood Treating Company Superfund site in Pensacola, FL.

PubMed

Karouna-Renier, Natalie K; Rao, K Ranga; Lanza, John J; Davis, Deeya A; Wilson, Patricia A

2007-10-01

The Escambia Wood Treating Company (ETC) Superfund site, Pensacola, FL, is contaminated with polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F), benzo(a)pyrene, lead and arsenic from pentachlorophenol (PCP), creosote, and other compounds used to treat utility poles and foundation pilings. Although ETC's operations ceased in 1982, soils in the areas surrounding the facility continue to exhibit elevated levels of contaminants attributable to ETC operations. In July 2000, individuals who may have been affected by contamination from the ETC site, including current and former residents and former workers and their household members were invited to participate in a study, which included a health and exposure history and routine blood analysis. We also conducted a toxicological health evaluation of a subset of these eligible workers/residents by analyzing serum levels of 17 PCDD/F congeners. Members of the ETC cohort exhibited elevated serum PCDD/F relative to the general population, and congener profiles in members of the cohort reflected patterns commonly observed in persons exposed to PCP. Hypertension prevalence in the cohort was found to correlate with PCDD/F levels, although no other significant relationships were identified with monitored health indices.

aLicante sUrgical Community Emergencies New Tool for the enUmeration of Morbidities: a simplified auditing tool for community-acquired gastrointestinal surgical emergencies.

PubMed

Villodre, Celia; Rebasa, Pere; Estrada, José Luís; Zaragoza, Carmen; Zapater, Pedro; Mena, Luís; Lluís, Félix

2016-11-01

In a previous study, we found that Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) overpredicts morbidity risk in emergency gastrointestinal surgery. Our aim was to find a POSSUM equation adjustment. A prospective observational study was performed on 2,361 patients presenting with a community-acquired gastrointestinal surgical emergency. The first 1,000 surgeries constituted the development cohort, the second 1,000 events were the first validation intramural cohort, and the remaining 361 cases belonged to a second validation extramural cohort. (1) A modified POSSUM equation was obtained. (2) Logistic regression was used to yield a statistically significant equation that included age, hemoglobin, white cell count, sodium and operative severity. (3) A chi-square automatic interaction detector decision tree analysis yielded a statistically significant equation with 4 variables, namely cardiac failure, sodium, operative severity, and peritoneal soiling. A modified POSSUM equation and a simplified scoring system (aLicante sUrgical Community Emergencies New Tool for the enUmeration of Morbidities [LUCENTUM]) are described. Both tools significantly improve prediction of surgical morbidity in community-acquired gastrointestinal surgical emergencies. Copyright © 2016 Elsevier Inc. All rights reserved.

Global Processing Speed in Children With Low Reading Ability and in Children and Adults With Typical Reading Ability: Exploratory Factor Analytic Models

PubMed Central

Peter, Beate; Matsushita, Mark; Raskind, Wendy H.

2013-01-01

Purpose To investigate processing speed as a latent dimension in children with dyslexia and children and adults with typical reading skills. Method Exploratory factor analysis (FA) was based on a sample of multigenerational families, each ascertained through a child with dyslexia. Eleven measures—6 of them timed—represented verbal and nonverbal processes, alphabet writing, and motor sequencing in the hand and oral motor system. FA was conducted in 4 cohorts (all children, a subset of children with low reading scores, a subset of children with typical reading scores, and adults with typical reading scores; total N = 829). Results Processing speed formed the first factor in all cohorts. Both measures of motor sequencing speed loaded on the speed factor with the other timed variables. Children with poor reading scores showed lower speed factor scores than did typical peers. The speed factor was negatively correlated with age in the adults. Conclusions The speed dimension was observed independently of participant cohort, gender, and reading ability. Results are consistent with a unified theory of processing speed as a quadratic function of age in typical development and with slowed processing in poor readers. PMID:21081672