CANCER INCIDENCE IN THE AGRICULTURAL HEALTH STUDY

EPA Science Inventory

The Agricultural Health Study (AHS) was undertaken to ascertain the etiology of cancers observed to be elevated in agricultural populations. Methods: The AHS is a large prospective, cohort study of private applicators and commercial applicators licensed to apply restricted use ...

Overview of the Japan Children’s Study 2004–2009; Cohort Study of Early Childhood Development

PubMed Central

Yamagata, Zentaro; Maeda, Tadahiko; Anme, Tokie; Sadato, Norihiro

2010-01-01

Background There are still a lot of unknown aspects about the childhood development of sociability which are based on neuroscientific basis. Purpose of the Japan Children’s Study (JCS) was to verify the normal process of child development of sociability; the trajectory and factors related development of sociability, and to collect findings and integrate the knowledge to make the plan of long-term and large scale cohort study. Methods A child cohort study underway in Japan since 2005. There are the cohort study including a infant cohort study at age of 4 months to 30 months and a preschool cohort study at age of 5 years old to 8 years old. Questionnaires, direct observation of children and cognitive testing were performed. Results In infant cohort study, 465 infants were recruited at 4 months and 367 children were followed up to 30 months, follow up rate was 78.9% and in the preschool cohort study, total 192 children (112 at 2005 and 80 at 2007) at age of 5 years old and 169 followed up to 6 years (follow up rate was 88.0%), and 79 children were followed up to 8 years old (follow up rate was 70.5%) old. Several new measurements to evaluate child sociability were developed. Some factors related to development of child sociability were found for example the ‘praise’ was related to child sociability in cohort study based on neuroscience findings. Conclusions Though the trajectory of child sociability development were not clarified, some significant factors related to development of sociability, and the basic findings to conduct a long-term and large scale cohort study were provided. PMID:20179361

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.

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.

The clinical course of low back pain: a meta-analysis comparing outcomes in randomised clinical trials (RCTs) and observational studies

PubMed Central

2014-01-01

Background Evidence suggests that the course of low back pain (LBP) symptoms in randomised clinical trials (RCTs) follows a pattern of large improvement regardless of the type of treatment. A similar pattern was independently observed in observational studies. However, there is an assumption that the clinical course of symptoms is particularly influenced in RCTs by mere participation in the trials. To test this assumption, the aim of our study was to compare the course of LBP in RCTs and observational studies. Methods Source of studies CENTRAL database for RCTs and MEDLINE, CINAHL, EMBASE and hand search of systematic reviews for cohort studies. Studies include individuals aged 18 or over, and concern non-specific LBP. Trials had to concern primary care treatments. Data were extracted on pain intensity. Meta-regression analysis was used to compare the pooled within-group change in pain in RCTs with that in cohort studies calculated as the standardised mean change (SMC). Results 70 RCTs and 19 cohort studies were included, out of 1134 and 653 identified respectively. LBP symptoms followed a similar course in RCTs and cohort studies: a rapid improvement in the first 6 weeks followed by a smaller further improvement until 52 weeks. There was no statistically significant difference in pooled SMC between RCTs and cohort studies at any time point:- 6 weeks: RCTs: SMC 1.0 (95% CI 0.9 to 1.0) and cohorts 1.2 (0.7to 1.7); 13 weeks: RCTs 1.2 (1.1 to 1.3) and cohorts 1.0 (0.8 to 1.3); 27 weeks: RCTs 1.1 (1.0 to 1.2) and cohorts 1.2 (0.8 to 1.7); 52 weeks: RCTs 0.9 (0.8 to 1.0) and cohorts 1.1 (0.8 to 1.6). Conclusions The clinical course of LBP symptoms followed a pattern that was similar in RCTs and cohort observational studies. In addition to a shared ‘natural history’, enrolment of LBP patients in clinical studies is likely to provoke responses that reflect the nonspecific effects of seeking and receiving care, independent of the study design. PMID:24607083

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.

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.

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.

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.

A class of non-linear exposure-response models suitable for health impact assessment applicable to large cohort studies of ambient air pollution.

PubMed

Nasari, Masoud M; Szyszkowicz, Mieczysław; Chen, Hong; Crouse, Daniel; Turner, Michelle C; Jerrett, Michael; Pope, C Arden; Hubbell, Bryan; Fann, Neal; Cohen, Aaron; Gapstur, Susan M; Diver, W Ryan; Stieb, David; Forouzanfar, Mohammad H; Kim, Sun-Young; Olives, Casey; Krewski, Daniel; Burnett, Richard T

2016-01-01

The effectiveness of regulatory actions designed to improve air quality is often assessed by predicting changes in public health resulting from their implementation. Risk of premature mortality from long-term exposure to ambient air pollution is the single most important contributor to such assessments and is estimated from observational studies generally assuming a log-linear, no-threshold association between ambient concentrations and death. There has been only limited assessment of this assumption in part because of a lack of methods to estimate the shape of the exposure-response function in very large study populations. In this paper, we propose a new class of variable coefficient risk functions capable of capturing a variety of potentially non-linear associations which are suitable for health impact assessment. We construct the class by defining transformations of concentration as the product of either a linear or log-linear function of concentration multiplied by a logistic weighting function. These risk functions can be estimated using hazard regression survival models with currently available computer software and can accommodate large population-based cohorts which are increasingly being used for this purpose. We illustrate our modeling approach with two large cohort studies of long-term concentrations of ambient air pollution and mortality: the American Cancer Society Cancer Prevention Study II (CPS II) cohort and the Canadian Census Health and Environment Cohort (CanCHEC). We then estimate the number of deaths attributable to changes in fine particulate matter concentrations over the 2000 to 2010 time period in both Canada and the USA using both linear and non-linear hazard function models.

The 2-Year Cosmetic Outcome of a Randomized Trial Comparing Prone and Supine Whole-Breast Irradiation in Large-Breasted Women

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

Veldeman, Liv, E-mail: liv.veldeman@uzgent.be; Department of Radiotherapy and Experimental Cancer Research, Ghent University, Ghent; Schiettecatte, Kimberly

Purpose: To report the 2-year cosmetic outcome of a randomized trial comparing prone and supine whole-breast irradiation in large-breasted patients. Methods and Materials: One hundred patients with a (European) cup size ≥C were included. Before and 2 years after radiation therapy, clinical endpoints were scored and digital photographs were taken with the arms alongside the body and with the arms elevated 180°. Three observers rated the photographs using the 4-point Harvard cosmesis scale. Cosmesis was also evaluated with the commercially available Breast Cancer Conservation Treatment.cosmetic results (BCCT.core) software. Results: Two-year follow-up data and photographs were available for 94 patients (47 supine treatedmore » and 47 prone treated). Patient and treatment characteristics were not significantly different between the 2 cohorts. A worsening of color change occurred more frequently in the supine than in the prone cohort (19/46 vs 10/46 patients, respectively, P=.04). Five patients in the prone group (11%) and 12 patients in the supine group (26%) presented with a worse scoring of edema at 2-year follow-up (P=.06). For retraction and fibrosis, no significant differences were found between the 2 cohorts, although scores were generally worse in the supine cohort. The cosmetic scoring by 3 observers did not reveal differences between the prone and supine groups. On the photographs with the hands up, 7 patients in the supine group versus none in the prone group had a worsening of cosmesis of 2 categories using the (BCCT.org) software (P=.02). Conclusion: With a limited follow-up of 2 years, better cosmetic outcome was observed in prone-treated than in supine-treated patients.« less

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.

Micro RNAs from DNA Viruses are Found Widely in Plasma in a Large Observational Human Population.

PubMed

Koupenova, Milka; Mick, Eric; Corkrey, Heather A; Huan, Tianxiao; Clancy, Lauren; Shah, Ravi; Benjamin, Emelia J; Levy, Daniel; Kurt-Jones, Evelyn A; Tanriverdi, Kahraman; Freedman, Jane E

2018-04-23

Viral infections associate with disease risk and select families of viruses encode miRNAs that control an efficient viral cycle. The association of viral miRNA expression with disease in a large human population has not been previously explored. We sequenced plasma RNA from 40 participants of the Framingham Heart Study (FHS, Offspring Cohort, Visit 8) and identified 3 viral miRNAs from 3 different human Herpesviridae. These miRNAs were mostly related to viral latency and have not been previously detected in human plasma. Viral miRNA expression was then screened in the plasma of 2763 participants of the remaining cohort utilizing high-throughput RT-qPCR. All 3 viral miRNAs associated with combinations of inflammatory or prothrombotic circulating biomarkers (sTNFRII, IL-6, sICAM1, OPG, P-selectin) but did not associate with hypertension, coronary heart disease or cancer. Using a large observational population, we demonstrate that the presence of select viral miRNAs in the human circulation associate with inflammatory biomarkers and possibly immune response, but fail to associate with overt disease. This study greatly extends smaller singular observations of viral miRNAs in the human circulation and suggests that select viral miRNAs, such as those for latency, may not impact disease manifestation.

A regularized variable selection procedure in additive hazards model with stratified case-cohort design.

PubMed

Ni, Ai; Cai, Jianwen

2018-07-01

Case-cohort designs are commonly used in large epidemiological studies to reduce the cost associated with covariate measurement. In many such studies the number of covariates is very large. An efficient variable selection method is needed for case-cohort studies where the covariates are only observed in a subset of the sample. Current literature on this topic has been focused on the proportional hazards model. However, in many studies the additive hazards model is preferred over the proportional hazards model either because the proportional hazards assumption is violated or the additive hazards model provides more relevent information to the research question. Motivated by one such study, the Atherosclerosis Risk in Communities (ARIC) study, we investigate the properties of a regularized variable selection procedure in stratified case-cohort design under an additive hazards model with a diverging number of parameters. We establish the consistency and asymptotic normality of the penalized estimator and prove its oracle property. Simulation studies are conducted to assess the finite sample performance of the proposed method with a modified cross-validation tuning parameter selection methods. We apply the variable selection procedure to the ARIC study to demonstrate its practical use.

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

Influence function based variance estimation and missing data issues in case-cohort studies.

PubMed

Mark, S D; Katki, H

2001-12-01

Recognizing that the efficiency in relative risk estimation for the Cox proportional hazards model is largely constrained by the total number of cases, Prentice (1986) proposed the case-cohort design in which covariates are measured on all cases and on a random sample of the cohort. Subsequent to Prentice, other methods of estimation and sampling have been proposed for these designs. We formalize an approach to variance estimation suggested by Barlow (1994), and derive a robust variance estimator based on the influence function. We consider the applicability of the variance estimator to all the proposed case-cohort estimators, and derive the influence function when known sampling probabilities in the estimators are replaced by observed sampling fractions. We discuss the modifications required when cases are missing covariate information. The missingness may occur by chance, and be completely at random; or may occur as part of the sampling design, and depend upon other observed covariates. We provide an adaptation of S-plus code that allows estimating influence function variances in the presence of such missing covariates. Using examples from our current case-cohort studies on esophageal and gastric cancer, we illustrate how our results our useful in solving design and analytic issues that arise in practice.

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.

Interval between onset of psoriasis and psoriatic arthritis comparing the UK Clinical Practice Research Datalink with a hospital-based cohort.

PubMed

Tillett, William; Charlton, Rachel; Nightingale, Alison; Snowball, Julia; Green, Amelia; Smith, Catherine; Shaddick, Gavin; McHugh, Neil

2017-12-01

To describe the time interval between the onset of psoriasis and PsA in the UK primary care setting and compare with a large, well-classified secondary care cohort. Patients with PsA and/or psoriasis were identified in the UK Clinical Practice Research Datalink (CPRD). The secondary care cohort comprised patients from the Bath PsA longitudinal observational cohort study. For incident PsA patients in the CPRD who also had a record of psoriasis, the time interval between PsA diagnosis and first psoriasis record was calculated. Comparisons were made with the time interval between diagnoses in the Bath cohort. There were 5272 eligible PsA patients in the CPRD and 815 in the Bath cohort. In both cohorts, the majority of patients (82.3 and 61.3%, respectively) had psoriasis before their PsA diagnosis or within the same calendar year (10.5 and 23.8%), with only a minority receiving their PsA diagnosis first (7.1 and 14.8%). Excluding those who presented with arthritis before psoriasis, the median time between diagnoses was 8 years [interquartile range (IQR) 2-15] in the CPRD and 7 years (IQR 0-20) in the Bath cohort. In the CPRD, 60.1 and 75.1% received their PsA diagnosis within 10 and 15 years of their psoriasis diagnosis, respectively; this was comparable with 57.2 and 67.7% in the Bath cohort. A similar distribution for the time interval between psoriasis and arthritis was observed in the CPRD and secondary care cohort. These data can inform screening strategies and support the validity of data from each cohort. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Regional variations in breast cancer among california teachers.

PubMed

Reynolds, Peggy; Hurley, Susan; Goldberg, Debbie E; Anton-Culver, Hoda; Bernstein, Leslie; Deapen, Dennis; Horn-Ross, Pamela L; Peel, David; Pinder, Richard; Ross, Ronald K; West, Dee; Wright, William E; Ziogas, Argyrios

2004-11-01

Observed regional differences in breast cancer incidence could provide valuable clues to the etiology of this disease. The pattern of historically higher breast cancer rates among residents of California's San Francisco Bay and Southern Coastal areas is evident in the disease experience among members of the California Teachers Study. This large cohort study has followed female professional school employees for cancer incidence since 1995 and has collected extensive information on breast cancer risk factors. Between 1996 and 1999, invasive breast cancer was diagnosed in 1562 of the 115,611 cohort members who could be geocoded to a California address in 1995 and who had no previous breast cancer diagnosis. Adjusted hazard rate ratios (HRs) were estimated through multivariate Cox proportional hazards modeling. Rates were higher for cohort members in the San Francisco Bay area (HR = 1.22; 95% confidence interval = 1.06-1.40) and Southern Coastal area (1.16; 1.04-1.30) compared with those in the rest of California. The distributions of variables representing socioeconomic status, urbanization, and personal risk factors were consistent with higher risks for cohort members residing in the San Francisco Bay and Southern Coastal areas. Adjustment for these factors, however, did not explain regional differences in incidence, resulting in HRs that remained elevated for these 2 areas. Regional differences in breast cancer incidence in this large, well-defined cohort are not easily explained by known risk factors.

Cancer and non-cancer mortality among French uranium cycle workers: the TRACY cohort

PubMed Central

Samson, Eric; Piot, Irwin; Zhivin, Sergey; Richardson, David B; Laroche, Pierre; Serond, Ana-Paula; Laurier, Dominique; Laurent, Olivier

2016-01-01

Objectives The health effects of internal contamination by radionuclides, and notably by uranium, are poorly characterised. New cohorts of uranium workers are needed to better examine these effects. This paper analyses for the first time the mortality profile of the French cohort of uranium cycle workers. It considers mortality from cancer and non-cancer causes. Methods The cohort includes workers employed at least 6 months between 1958 and 2006 in French companies involved in the production of nuclear fuel. Vital status and causes of death were collected from French national registries. Workers were followed-up from 1 January 1968 to 31 December 2008. Standardised mortality ratios (SMRs) were computed based on mortality rates for the French general population. Results The cohort includes 12 649 workers (88% men). The average length of follow-up is 27 years and the mean age at the end of the study is 60 years. Large mortality deficits are observed for non-cancer causes of death such as non-cancer respiratory diseases (SMR=0.51 (0.41 to 0.63)) and circulatory diseases (SMR=0.68 (0.62 to 0.74)). A mortality deficit of lower magnitude is also observed for all cancers combined (SMR (95% CI): 0.76 (0.71 to 0.81)). Pleural mesothelioma is elevated (SMR=2.04 (1.19 to 3.27)). Conclusions A healthy worker effect is observed in this new cohort of workers involved in the uranium cycle. Collection of individual information on internal uranium exposure as well as other risk factors is underway, to allow for the investigation of uranium-related risks. PMID:27048635

Cancer and non-cancer mortality among French uranium cycle workers: the TRACY cohort.

PubMed

Samson, Eric; Piot, Irwin; Zhivin, Sergey; Richardson, David B; Laroche, Pierre; Serond, Ana-Paula; Laurier, Dominique; Laurent, Olivier

2016-04-05

The health effects of internal contamination by radionuclides, and notably by uranium, are poorly characterised. New cohorts of uranium workers are needed to better examine these effects. This paper analyses for the first time the mortality profile of the French cohort of uranium cycle workers. It considers mortality from cancer and non-cancer causes. The cohort includes workers employed at least 6 months between 1958 and 2006 in French companies involved in the production of nuclear fuel. Vital status and causes of death were collected from French national registries. Workers were followed-up from 1 January 1968 to 31 December 2008. Standardised mortality ratios (SMRs) were computed based on mortality rates for the French general population. The cohort includes 12,649 workers (88% men). The average length of follow-up is 27 years and the mean age at the end of the study is 60 years. Large mortality deficits are observed for non-cancer causes of death such as non-cancer respiratory diseases (SMR=0.51 (0.41 to 0.63)) and circulatory diseases (SMR=0.68 (0.62 to 0.74)). A mortality deficit of lower magnitude is also observed for all cancers combined (SMR (95% CI): 0.76 (0.71 to 0.81)). Pleural mesothelioma is elevated (SMR=2.04 (1.19 to 3.27)). A healthy worker effect is observed in this new cohort of workers involved in the uranium cycle. Collection of individual information on internal uranium exposure as well as other risk factors is underway, to allow for the investigation of uranium-related risks. 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/

Accuracy of the Atherosclerotic Cardiovascular Risk Equation in a Large Contemporary, Multiethnic Population.

PubMed

Rana, Jamal S; Tabada, Grace H; Solomon, Matthew D; Lo, Joan C; Jaffe, Marc G; Sung, Sue Hee; Ballantyne, Christie M; Go, Alan S

2016-05-10

The accuracy of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Risk Equation for atherosclerotic cardiovascular disease (ASCVD) events in contemporary and ethnically diverse populations is not well understood. The goal of this study was to evaluate the accuracy of the 2013 ACC/AHA Pooled Cohort Risk Equation within a large, multiethnic population in clinical care. The target population for consideration of cholesterol-lowering therapy in a large, integrated health care delivery system population was identified in 2008 and followed up through 2013. The main analyses excluded those with known ASCVD, diabetes mellitus, low-density lipoprotein cholesterol levels <70 or ≥190 mg/dl, prior lipid-lowering therapy use, or incomplete 5-year follow-up. Patient characteristics were obtained from electronic medical records, and ASCVD events were ascertained by using validated algorithms for hospitalization databases and death certificates. We compared predicted versus observed 5-year ASCVD risk, overall and according to sex and race/ethnicity. We additionally examined predicted versus observed risk in patients with diabetes mellitus. Among 307,591 eligible adults without diabetes between 40 and 75 years of age, 22,283 were black, 52,917 were Asian/Pacific Islander, and 18,745 were Hispanic. We observed 2,061 ASCVD events during 1,515,142 person-years. In each 5-year predicted ASCVD risk category, observed 5-year ASCVD risk was substantially lower: 0.20% for predicted risk <2.50%; 0.65% for predicted risk 2.50% to <3.75%; 0.90% for predicted risk 3.75% to <5.00%; and 1.85% for predicted risk ≥5.00% (C statistic: 0.74). Similar ASCVD risk overestimation and poor calibration with moderate discrimination (C statistic: 0.68 to 0.74) were observed in sex, racial/ethnic, and socioeconomic status subgroups, and in sensitivity analyses among patients receiving statins for primary prevention. Calibration among 4,242 eligible adults with diabetes was improved, but discrimination was worse (C statistic: 0.64). In a large, contemporary "real-world" population, the ACC/AHA Pooled Cohort Risk Equation substantially overestimated actual 5-year risk in adults without diabetes, overall and across sociodemographic subgroups. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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.

Workload and management of childhood fever at general practice out-of-hours care: an observational cohort study

PubMed Central

de Bont, Eefje G P M; Lepot, Julie M M; Hendrix, Dagmar A S; Loonen, Nicole; Guldemond-Hecker, Yvonne; Dinant, Geert-Jan; Cals, Jochen W L

2015-01-01

Objective Even though childhood fever is mostly self-limiting, children with fever constitute a considerable workload in primary care. Little is known about the number of contacts and management during general practitioners’ (GPs) out-of-hours care. We investigated all fever related telephone contacts, consultations, antibiotic prescriptions and paediatric referrals of children during GP out-of-hours care within 1 year. Design Observational cohort study. Setting and patients We performed an observational cohort study at a large Dutch GP out-of-hours service. Children (<12 years) whose parents contacted the GP out-of-hours service for a fever related illness in 2012 were included. Main outcome measures Number of contacts and consultations, antibiotic prescription rates and paediatric referral rates. Results We observed an average of 14.6 fever related contacts for children per day at GP out-of-hours services, with peaks during winter months. Of 17 170 contacts in 2012, 5343 (31.1%) were fever related and 70.0% resulted in a GP consultation. One in four consultations resulted in an antibiotic prescription. Prescriptions increased by age and referrals to secondary care decreased by age (p<0.001). The majority of parents (89.5%) contacted the out-of-hours service only once during a fever episode (89.5%) and 7.6% of children were referred to secondary care. Conclusions This study shows that childhood fever does account for a large workload at GP out-of-hours services. One in three contacts is fever related and 70% of those febrile children are called in to be assessed by a GP. One in four consultations for childhood fever results in antibiotic prescribing and most consultations are managed in primary care without referral. PMID:25991452

Clinical efficacy of Avène hydrotherapy measured in a large cohort of more than 10,000 atopic or psoriatic patients.

PubMed

Merial-Kieny, C; Mengual, X; Guerrero, D; Sibaud, V

2011-02-01

Atopic dermatitis (AD) and psoriasis are chronic skin conditions. Local or systemic treatments are effective, but their effects are transient. Hydrotherapy, used alone or in combination with other treatments, could be considered as one form of care in providing effective management of these dermatoses. The objective of this observational study was to evaluate the benefit of a 3-week treatment at Avène Hydrotherapy Centre in a very large cohort of patients suffering from atopic dermatitis and psoriasis and to assess the treatment benefits on patients undergoing hydrotherapy for two consecutive years. This 8-year observational study analysed 14,328 records of patients having a dermatological disease and who came to Avène Hydrotherapy Centre for a 3-week treatment between 2001 and 2009. Among them, patients were suffering from atopic dermatitis (n = 5916) and psoriasis (n = 4887). On admission on D0 (day 0) and at the end of cure on D18 (day 18), the severity of AD and psoriasis were evaluated by SCORing Atopic Dermatitis (SCORAD) and Psoriasis Area and Severity Index (PASI), respectively. In order to assess the cumulative effect of the hydrotherapy treatment, the evolution of SCORAD or PASI of patients who came 2 years in a row was also calculated. A significant improvement in SCORAD was observed between D0 and D18 (-41.6%) (P < 0.0001) and similarly, a significant reduction in PASI was noted between D0 and D18 (-54.4%) (P < 0.0001) after 3-weeks of hydrotherapy. PASI 50 and PASI 75 were 64.3% and 19.5%, respectively. For atopic patients (n = 1102) or patients suffering from psoriasis (n = 833) who came for two consecutive years, a significant SCORAD and PASI improvement was observed on D0 of the second year when compared with D0 of the previous year (P < 0.0001). This study is the first observational study in such a large cohort demonstrating the benefit of a 3-week treatment at the Avène Hydrotherapy Centre for atopic and psoriatic patients. © 2010 The Authors. JEADV © 2010 European Academy of Dermatology and Venereology.

Mode of delivery is not associated with celiac disease.

PubMed

Dydensborg Sander, Stine; Hansen, Anne Vinkel; Størdal, Ketil; Andersen, Anne-Marie Nybo; Murray, Joseph A; Husby, Steffen

2018-01-01

The purpose of this study was to investigate the association between mode of delivery and the risk of celiac disease in two large population-based birth cohorts with different prevalence of diagnosed celiac disease. This is an observational register-based cohort study using two independent population cohorts. We used data from administrative registers and health administrative registers from Denmark and Norway and linked the data at the individual level. We included all children who were born in Denmark from January 1, 1995 to December 31, 2010 and all children who were born in Norway from January 1, 2004 to December 31, 2012. We included 1,051,028 children from Denmark. Cesarean sections were registered for 196,512 children (18.9%). Diagnosed celiac disease was registered for 1,395 children (0.13%). We included 537,457 children from Norway. Cesarean sections were registered for 90,128 children (16.8%). Diagnosed celiac disease was registered for 1,919 children (0.35%). We found no association between the mode of delivery and the risk of diagnosed celiac disease. The adjusted odds ratio for celiac disease for children delivered by any type of cesarean section compared to vaginal delivery was 1.11 (95% CI: 0.96-1.29) in the Danish cohort and 0.96 (95% CI: 0.84-1.09) in the Norwegian cohort. The adjusted odds ratio for celiac disease for children delivered by elective cesarean section compared to vaginal delivery was 1.20 (95% CI: 1.00-1.43) in the Danish cohort and 0.96 (95% CI: 0.79-1.17) in the Norwegian cohort. In this large registry-based study, mode of delivery was not associated with an increased risk of diagnosed celiac disease.

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.

A prospective study of fetal head growth, autistic traits and autism spectrum disorder

PubMed Central

Blanken, Laura M. E.; Dass, Alena; Alvares, Gail; van der Ende, Jan; Schoemaker, Nikita K.; El Marroun, Hanan; Hickey, Martha; Pennell, Craig; White, Scott; Maybery, Murray T.; Dissanayake, Cheryl; Jaddoe, Vincent W. V.; Verhulst, Frank C.; Tiemeier, Henning; McIntosh, Will; Whitehouse, Andrew

2018-01-01

Altered trajectories of brain growth are often reported in Autism Spectrum Disorder (ASD), particularly during the first year of life. However, less is known about prenatal head growth trajectories, and no study has examined the relation with postnatal autistic symptom severity. The current study prospectively examined the association between fetal head growth and the spectrum of autistic symptom severity in two large population‐based cohorts, including a sample of individuals with clinically diagnosed ASD. This study included 3,820 children from two longitudinal prenatal cohorts in The Netherlands and Australia, comprising 60 individuals with a confirmed diagnosis of ASD. Latent growth curve models were used to examine the relationship between fetal head circumference measured at three different time points and autistic traits measured in postnatal life using either the Social Responsiveness Scale or the Autism‐Spectrum Quotient. While lower initial prenatal HC was weakly associated with increasing autistic traits in the Dutch cohort, this relationship was not observed in the Australian cohort, nor when the two cohorts were analysed together. No differences in prenatal head growth were found between individuals with ASD and controls. This large population‐based study identified no consistent association across two cohorts between prenatal head growth and postnatal autistic traits. Our mixed findings suggest that further research in this area is needed. Autism Res 2018, 11: 602–612. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. Lay Summary It is not known whether different patterns of postnatal brain growth in Autism Spectrum Disorder (ASD) also occurs prenatally. We examined fetal head growth and autistic symptoms in two large groups from The Netherlands and Australia. Lower initial prenatal head circumference was associated with autistic traits in the Dutch, but not the Australian, group. No differences in head growth were found in individuals with ASD and controls when the data was combined. Our mixed findings suggest that more research in this area is needed. PMID:29356450

Simplified methods of determining treatment retention in Malawi: ART cohort reports vs. pharmacy stock cards.

PubMed

Chan, A K; Singogo, E; Changamire, R; Ratsma, Y E C; Tassie, J-M; Harries, A D

2012-06-21

Rapid scale-up of antiretroviral therapy (ART) has challenged the health system in Malawi to monitor large numbers of patients effectively. To compare two methods of determining retention on treatment: quarterly ART clinic data aggregation vs. pharmacy stock cards. Between October 2010 and March 2011, data on ART outcomes were extracted from monitoring tools at five facilities. Pharmacy data on ART consumption were extracted. Workload for each method was observed and timed. We used intraclass correlation and Bland-Altman plots to compare the agreeability of both methods to determine treatment retention. There is wide variability between ART clinic cohort data and pharmacy data to determine treatment retention due to divergence in data at sites with large numbers of patients. However, there is a non-significant trend towards agreeability between the two methods (intraclass correlation coefficient > 0.9; P > 0.05). Pharmacy stock card monitoring is more time-efficient than quarterly ART data aggregation (81 min vs. 573 min). In low-resource settings, pharmacy records could be used to improve drug forecasting and estimate ART retention in a more time-efficient manner than quarterly data aggregation; however, a necessary precondition would be capacity building around pharmacy data management, particularly for large-sized cohorts.

Construction of Student Groups Using Belbin: Supporting Group Work in Environmental Management

ERIC Educational Resources Information Center

Smith, Mark; Polglase, Giles; Parry, Carolyn

2012-01-01

Belbin team role self and observer perceptions were applied to a large cohort (145) of Geography, Earth and Environmental Sciences undergraduates in a module assessed through two separate group projects. Students self-selected groups for the first project; for the second, groups were more "balanced." Results show slight improvement in…

Education, the Brain and Dementia: Neuroprotection or Compensation?

ERIC Educational Resources Information Center

Brayne, Carol; Ince, Paul G.; Keage, Hannah A. D.; McKeith, Ian G.; Matthews, Fiona E.; Polvikoski, Tuomo; Sulkava, Raimo

2010-01-01

The potential protective role of education for dementia is an area of major interest. Almost all older people have some pathology in their brain at death but have not necessarily died with dementia. We have explored these two observations in large population-based cohort studies (Epidemiological Clinicopathological Studies in Europe; EClipSE) in…

Cohort profile: LIFEWORK, a prospective cohort study on occupational and environmental risk factors and health in the Netherlands

PubMed Central

Peeters, Petra H; Korevaar, Joke C; Bueno-de-Mesquita, Bas; Verschuren, W M Monique; Verheij, Robert A; Pieterson, Inka; van Leeuwen, Flora E

2018-01-01

Purpose LIFEWORK is a large federated prospective cohort established in the Netherlands to quantify the health effects of occupational and environmental exposures. This cohort is also the Dutch contribution to the international Cohort Study of Mobile Phone Use and Health (COSMOS). In this paper, we describe the study design, ongoing data collection, baseline characteristics of participants and the repeatability of key questionnaire items. Participants 88 466 participants were enrolled in three cohort studies in 2011–2012. Exposure information was collected by a harmonised core questionnaire, or modelled based on occupational and residential histories; domains include air pollution (eg, nitrogen dioxide (NO2), particulate matter with diameter ≤2.5 µm (PM2.5)), noise, electromagnetic fields (EMF), mobile phone use, shift work and occupational chemical exposures. Chronic and subacute health outcomes are assessed by self-report and through linkage with health registries. Findings to date Participants had a median age of 51 years at baseline (range 19–87), and the majority are female (90%), with nurses being over-represented. Median exposure levels of NO2, PM2.5, EMF from base stations and noise at the participants’ home addresses at baseline were 22.9 µg/m3, 16.6 µg/m3, 0.003 mWm2 and 53.1 dB, respectively. Twenty-two per cent of participants reported to have started using a mobile phone more than 10 years prior to baseline. Repeatability for self-reported exposures was moderate to high (weighted kappa range: 0.69–1) for a subset of participants (n=237) who completed the questionnaire twice. Future plans We are actively and passively observing participants; we plan to administer a follow-up questionnaire every 4–5 years—the first follow-up will be completed in 2018—and linkage to cause-of-death and cancer registries occurs on a (bi)annual basis. This prospective cohort offers a unique, large and rich resource for research on contemporary occupational and environmental health risks and will contribute to the large international COSMOS study on mobile phone use and health. PMID:29431129

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.

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.

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

Designing Reliable Cohorts of Cardiac Patients across MIMIC and eICU

PubMed Central

Chronaki, Catherine; Shahin, Abdullah; Mark, Roger

2016-01-01

The design of the patient cohort is an essential and fundamental part of any clinical patient study. Knowledge of the Electronic Health Records, underlying Database Management System, and the relevant clinical workflows are central to an effective cohort design. However, with technical, semantic, and organizational interoperability limitations, the database queries associated with a patient cohort may need to be reconfigured in every participating site. i2b2 and SHRINE advance the notion of patient cohorts as first class objects to be shared, aggregated, and recruited for research purposes across clinical sites. This paper reports on initial efforts to assess the integration of Medical Information Mart for Intensive Care (MIMIC) and Philips eICU, two large-scale anonymized intensive care unit (ICU) databases, using standard terminologies, i.e. LOINC, ICD9-CM and SNOMED-CT. Focus of this work is lab and microbiology observations and key demographics for patients with a primary cardiovascular ICD9-CM diagnosis. Results and discussion reflecting on reference core terminology standards, offer insights on efforts to combine detailed intensive care data from multiple ICUs worldwide. PMID:27774488

A large observational study to concurrently assess persistence of measles specific B-cell and T-cell immunity in individuals following two doses of MMR vaccine

PubMed Central

Haralambieva, Iana H.; Ovsyannikova, Inna G.; O’Byrne, Megan; Pankratz, V. Shane; Jacobson, Robert M.; Poland, Gregory A.

2011-01-01

The measurement of measles-specific neutralizing antibodies, directed against the surface measles virus hemagglutinin and fusion proteins, is considered the gold standard in measles serology. We assessed functional measles-specific neutralizing antibody levels in a racially diverse cohort of 763 young healthy adolescents after receipt of two doses of measles-mumps-rubella vaccine, by the use of an automated plaque reduction microneutralization (PRMN) assay, and evaluated their relevance to protective antibody levels, as well as their associations with demographic and clinical variables. We also concurrently assessed measles-specific IFNγ Elispot responses and their relation to the observed antibody concentrations. The geometric mean titer for our cohort was 832 mIU/mL (95% CIs: 776; 891). Sixty-eight subjects (8.9%) had antibody concentrations of less than the protective threshold of 210 mIU/mL (corresponding to PRMN titer of 120; suggesting protection against symptomatic disease), and 177 subjects (23.2%) demonstrated persisting antibody concentrations above 1,841 mIU/mL (corresponding to PRMN titer of 1,052; suggesting total protection against viral infection), 7.4 years after vaccination, in the absence of wild-type virus boosting. The mean measles-specific IFNγ Elispot response for our cohort was 46 (95% CIs: 43; 49) IFNγ-positive spots per 200,000 cells with no relation of cellular immunity measures to the observed antibody concentrations. No significant associations between antibody titers and demographic and clinical variables, including gender and race, were observed in our study. In conclusion, in a large observational study of measles immunity, we used an automated high-throughput measles virus-specific neutralization assay to measure humoral immunity, and concurrently determined measles-specific cellular immunity to aid the assessment of potential susceptibility to measles in vaccinated populations. PMID:21539880

Benefits of the Mediterranean diet beyond the Mediterranean Sea and beyond food patterns.

PubMed

Martínez-González, Miguel A

2016-10-14

Abundant and growing evidence has accrued to demonstrate that the traditional Mediterranean diet is likely to be the ideal dietary pattern for the prevention of cardiovascular disease. A landmark randomized trial (PREDIMED) together with many well-conducted long-term observational prospective cohort studies support this causal effect.A new, large British cohort study by Tong et al. assessing the association between adherence to the Mediterranean diet and cardiovascular disease was recently published in BMC Medicine. Using a superb methodology, they followed-up 23,902 participants for 12.2 years on average and observed several thousand incident cases.The results of this cohort study showed a significant beneficial effect of the Mediterranean diet on cardiovascular events. These findings support the transferability of this dietary pattern beyond the shores of the Mediterranean Sea. The authors provided measures of population impact in cardiovascular prevention and estimated that 19,375 cases of cardiovascular death would be prevented each year in the UK by promoting the Mediterranean Diet.Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0677-4 .

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.

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.

Occupational exposures and Parkinson's disease mortality in a prospective Dutch cohort.

PubMed

Brouwer, Maartje; Koeman, Tom; van den Brandt, Piet A; Kromhout, Hans; Schouten, Leo J; Peters, Susan; Huss, Anke; Vermeulen, Roel

2015-06-01

We investigated the association between six occupational exposures (ie, pesticides, solvents, metals, diesel motor emissions (DME), extremely low frequency magnetic fields (ELF-MF) and electric shocks) and Parkinson's disease (PD) mortality in a large population-based prospective cohort study. The Netherlands Cohort Study on diet and cancer enrolled 58,279 men and 62,573 women aged 55-69 years in 1986. Participants were followed up for cause-specific mortality over 17.3 years, until December 2003, resulting in 402 male and 207 female PD deaths. Following a case-cohort design, a subcohort of 5,000 participants was randomly sampled from the complete cohort. Information on occupational history and potential confounders was collected at baseline. Job-exposure matrices were applied to assign occupational exposures. Associations with PD mortality were evaluated using Cox regression. Among men, elevated HRs were observed for exposure to pesticides (eg, ever high exposed, HR 1.27, 95% CI 0.86 to 1.88) and ever high exposed to ELF-MF (HR 1.54, 95% CI 1.00 to 2.36). No association with exposure duration or trend in cumulative exposure was observed for any of the occupational exposures. Results among women were unstable due to small numbers of high-exposed women. Associations with PD mortality were observed for occupational exposure to pesticides and ELF-MF. However, the weight given to these findings is limited by the absence of a monotonic trend with either duration or cumulative exposure. No associations were found between PD mortality and occupational exposure to solvents, metals, DME or electric shocks. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Investigating a Nigerian XXL-Cohort Wiki-Learning Experience: Observation, Feedback and Reflection

ERIC Educational Resources Information Center

Aborisade, Peter

2009-01-01

A regular feature of the Nigerian tertiary education context is large numbers of students crammed into small classrooms or lecture theatres. This context had long begged for the creation of innovative learning spaces and adoption of engaging pedagogies. Recourse to technology support and experimenting with the WIKI as a learning tool at the…

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 ...

Investigation of multiple susceptibility loci for inflammatory bowel disease in an Italian cohort of patients.

PubMed

Latiano, Anna; Palmieri, Orazio; Latiano, Tiziana; Corritore, Giuseppe; Bossa, Fabrizio; Martino, Giuseppina; Biscaglia, Giuseppe; Scimeca, Daniela; Valvano, Maria Rosa; Pastore, Maria; Marseglia, Antonio; D'Incà, Renata; Andriulli, Angelo; Annese, Vito

2011-01-01

Recent GWAs and meta-analyses have outlined about 100 susceptibility genes/loci for inflammatory bowel diseases (IBD). In this study we aimed to investigate the influence of SNPs tagging the genes/loci PTGER4, TNFSF15, NKX2-3, ZNF365, IFNG, PTPN2, PSMG1, and HLA in a large pediatric- and adult-onset IBD Italian cohort. Eight SNPs were assessed in 1,070 Crohn's disease (CD), 1,213 ulcerative colitis (UC), 557 of whom being diagnosed at the age of ≤16 years, and 789 healthy controls. Correlations with sub-phenotypes and major variants of NOD2 gene were investigated. The SNPs tagging the TNFSF15, NKX2-3, ZNF365, and PTPN2 genes were associated with CD (P values ranging from 0.037 to 7×10(-6)). The SNPs tagging the PTGER4, NKX2-3, ZNF365, IFNG, PSMG1, and HLA area were associated with UC (P values 0.047 to 4×10(-5)). In the pediatric cohort the associations of TNFSF15, NKX2-3 with CD, and PTGER4, NKX2-3, ZNF365, IFNG, PSMG1 with UC, were confirmed. Association with TNFSF15 and pediatric UC was also reported. A correlation with NKX2-3 and need for surgery (P  =  0.038), and with HLA and steroid-responsiveness (P  =  0.024) in UC patients was observed. Moreover, significant association in our CD cohort with TNFSF15 SNP and colonic involvement (P  =  0.021), and with ZNF365 and ileal location (P  =  0.024) was demonstrated. We confirmed in a large Italian cohort the associations with CD and UC of newly identified genes, both in adult and pediatric cohort of patients, with some influence on sub-phenotypes.

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

Serum 25-hydroxyvitamin d and cancer risk in older adults: results from a large German prospective cohort study.

PubMed

Ordóñez-Mena, José M; Schöttker, Ben; Haug, Ulrike; Müller, Heiko; Köhrle, Josef; Schomburg, Lutz; Holleczek, Bernd; Brenner, Hermann

2013-05-01

Several observational studies assessed the relationship between serum 25-hydroxyvitamin D [25(OH)D] concentrations and the risk of cancer but results were inconclusive. We measured 25(OH)D concentrations in a population-based cohort study of 9,949 men and women ages 50 to 74 years in Saarland, Germany. Comprehensively adjusted Cox regression models were applied to estimate HRs and 95% confidence intervals (CI) for the association between season-standardized 25(OH)D concentrations and total and site-specific cancer incidence. Overall, during a median of 8 years of follow-up, 873 subjects developed cancer; the most common being prostate (171), breast (137), lung (136), and colorectal (136) cancer. Low season-standardized 25(OH)D (<30, 35, 40, or 36 nmol/L in winter, spring, summer, and autumn, respectively) was neither significantly associated with total cancer incidence (HR, 1.10; 95% CI, 0.93-1.30) nor with site-specific cancer incidence. However, a significantly increased overall cancer risk was observed for low 25(OH)D among men, nonobese subjects and subjects reporting low fish consumption and for high 25(OH)D in nonsmokers and nonobese subjects. Accordingly, restricted cubic splines to investigate dose-response relationships curves showed an inverse association of 25(OH)D levels and total cancer risk in men but not in women. 25(OH)D concentrations were significantly associated with overall cancer incidence in subgroups of this large cohort from Germany. No significant association was observed with site-specific cancers but this could be due to a limited statistical power for these endpoints. Further research should clarify whether and to what extent specific risk groups might profit from vitamin D supplementation.

Risks for central nervous system diseases among mobile phone subscribers: a Danish retrospective cohort study.

PubMed

Schüz, Joachim; Waldemar, Gunhild; Olsen, Jørgen H; Johansen, Christoffer

2009-01-01

The aim of this study was to investigate a possible link between cellular telephone use and risks for various diseases of the central nervous system (CNS). We conducted a large nationwide cohort study of 420 095 persons whose first cellular telephone subscription was between 1982 and 1995, who were followed through 2003 for hospital contacts for a diagnosis of a CNS disorder. Standardized hospitalization ratios (SHRs) were derived by dividing the number of hospital contacts in the cohort by the number expected in the Danish population. The SHRs were increased by 10-20% for migraine and vertigo. No associations were seen for amyotrophic lateral sclerosis, multiple sclerosis or epilepsy in women. SHRs decreased by 30-40% were observed for dementia (Alzheimer disease, vascular and other dementia), Parkinson disease and epilepsy among men. In analyses restricted to subscribers of 10 years or more, the SHRs remained similarly increased for migraine and vertigo and similarly decreased for Alzheimer disease and other dementia and epilepsy (in men); the other SHRs were close to unity. In conclusion, the excesses of migraine and vertigo observed in this first study on cellular telephones and CNS disease deserve further attention. An interplay of a healthy cohort effect and reversed causation bias due to prodromal symptoms impedes detection of a possible association with dementia and Parkinson disease. Identification of the factors that result in a healthy cohort might be of interest for elucidation of the etiology of these diseases.

[Linkage of large secondary and registry data sources with data of cohort studies : usage of a dual potential].

PubMed

Jacobs, Svenja; Stallmann, Christoph; Pigeot, Iris

2015-08-01

Cohort studies provide the best evidence of all epidemiological observational studies for the identification of causal relationships between risk factors and diseases. However, this design may lead to drawbacks that may affect the validity and reliability of the results. This follows in particular from systematic errors, such as selection bias or recall bias. One possibility to avoid or counteract some of these drawbacks is to link primary data from cohort studies with secondary and register data. The linkage of these data may also be used for mutual validations. Data that were previously linked with primary data within the context of cohort studies in Germany were obtained from statutory health insurances and pensions as well as data from the Federal Employment Agency and cancer registries. All these data have two features in common: First, they all cover detailed information about a large population and over a long period of time. Second, all sources are in principle able to provide data on an individual level such that an individual data linkage, e.g. with primary data, is possible. However, use and linkage of each of these data sources are restricted by several limitations. These have to be accounted for as well as numerous legal restrictions that exist in Germany to especially prevent the misuse of social data.

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.

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.

Asbestos and cancer: a cohort followed up to death.

PubMed Central

Enterline, P E; Hartley, J; Henderson, V

1987-01-01

The mortality experience of 1074 white men who retired from a United States asbestos company during the period 1941-67 and who were exposed to asbestos working as production and maintenance employees for the company is reported to the end of 1980 when 88% of this cohort was known to be dead. As noted in earlier reports the mortality for respiratory and gastrointestinal cancer was raised. A more detailed examination of causes of death shows that the excess in gastrointestinal cancer was largely due to a statistically significant excess in stomach cancer. A statistically significant excess was also noted for kidney cancer, cancer of the eye, and non-malignant respiratory disease. Eight deaths from malignant mesothelioma were observed, two of which were peritoneal. Asbestos exposures for these mesothelioma cases were low relative to other members of the cohort. Continuing follow up of this cohort shows a dose response relation for respiratory cancer that has become increasingly linear. Standardised mortality ratios peaked 10 to 15 years after retirement and were relatively constant at around 250 in each five year interval starting in 1950. This excess might have been detected as early as 1960 but certainly by 1965. The mortality experience of this cohort reflects the ultimate effects of asbestos since nearly all of the cohort has now died. PMID:3606968

Integrating 400 million variants from 80,000 human samples with extensive annotations: towards a knowledge base to analyze disease cohorts.

PubMed

Hakenberg, Jörg; Cheng, Wei-Yi; Thomas, Philippe; Wang, Ying-Chih; Uzilov, Andrew V; Chen, Rong

2016-01-08

Data from a plethora of high-throughput sequencing studies is readily available to researchers, providing genetic variants detected in a variety of healthy and disease populations. While each individual cohort helps gain insights into polymorphic and disease-associated variants, a joint perspective can be more powerful in identifying polymorphisms, rare variants, disease-associations, genetic burden, somatic variants, and disease mechanisms. We have set up a Reference Variant Store (RVS) containing variants observed in a number of large-scale sequencing efforts, such as 1000 Genomes, ExAC, Scripps Wellderly, UK10K; various genotyping studies; and disease association databases. RVS holds extensive annotations pertaining to affected genes, functional impacts, disease associations, and population frequencies. RVS currently stores 400 million distinct variants observed in more than 80,000 human samples. RVS facilitates cross-study analysis to discover novel genetic risk factors, gene-disease associations, potential disease mechanisms, and actionable variants. Due to its large reference populations, RVS can also be employed for variant filtration and gene prioritization. A web interface to public datasets and annotations in RVS is available at https://rvs.u.hpc.mssm.edu/.

Historical Improvements in Well-Being Do Not Hold in Late Life: Birth- and Death-Year Cohorts in the US and Germany

PubMed Central

Hülür, Gizem; Ram, Nilam; Gerstorf, Denis

2015-01-01

One key objective of lifespan research is to examine how individual development is shaped by the historical time people live in. Secular trends favoring later-born cohorts on fluid cognitive abilities have been widely documented, but findings are mixed for well-being. It remains an open question whether secular increases in well-being seen in earlier phases of life also manifest in the last years of life. To examine this possibility, we made use of longitudinal data obtained from the mid 1980s until the late 2000s in two large national samples in the US (Health and Retirement Study, HRS) and Germany (German Socio-Economic Panel, SOEP). We operationally defined historical time from two complementary perspectives: birth-year cohorts based on the years people were born (earlier: 1930s vs. later: 1940s); and death-year cohorts based on the years people died (earlier: 1990s vs. later: 2000s). To control for relevant covariates, we used case-matched groups based on age (at death) and education and covaried for gender, health, and number of observations. Results from both countries revealed that well-being in old age was indeed developing at higher levels among later-born cohorts. However, for later-deceased cohorts, no evidence for secular increases in well-being was found. To the contrary, later-dying SOEP participants reported lower levels of well-being at age 75 years and 2 years prior to death and experienced steeper late-life declines. Our results suggest that secular increases in well-being observed in old age do not manifest in late-life where “manufactured” survival may be exacerbating age- and mortality-related declines. PMID:26098582

Descriptive epidemiology and prior healthcare utilization of patients in the Spine Patient Outcomes Research Trial's (SPORT) three observational cohorts: disc herniation, spinal stenosis, and degenerative spondylolisthesis.

PubMed

Cummins, Justin; Lurie, Jon D; Tosteson, Tor D; Hanscom, Brett; Abdu, William A; Birkmeyer, Nancy J O; Herkowitz, Harry; Weinstein, James

2006-04-01

Prospective observational cohorts. To describe sociodemographic and clinical features, and nonoperative (medical) resource utilization before enrollment, in patients who are candidates for surgical intervention for intervertebral disc herniation (IDH), spinal stenosis (SpS), and degenerative spondylolisthesis (DS) according to SPORT criteria. Intervertebral disc herniation, spinal stenosis, and degenerative spondylolisthesis with stenosis are the three most common diagnoses of low back and leg symptoms for which surgery is performed. There is a paucity of descriptive literature examining large patient cohorts for the relationships among baseline characteristics and medical resource utilization with these three diagnoses. The Spine Patient Outcomes Research Trial (SPORT) conducts three randomized and three observational cohort studies of surgical and nonsurgical treatments for patients with IDH, SpS, and DS. Baseline data include demographic information, prior treatments received, and functional status measured by SF-36 and the Oswestry Disability Index (ODI-AAOS/Modems version). The data presented represent all 1,411 patients (743 IDH, 365 SpS, 303 DS) enrolled in the SPORT observational cohorts. Multiple logistic regression was used to generate independent predictors of utilization adjusted for sociodemographic variables, diagnosis, and duration of symptoms. The average age was 41 years for the IDH group, 64 years for the SpS group, and 66 years for the DS group. At enrollment, IDH patients presented with the most pain as reported on the SF-36 (BP 26.3 vs. 33.2 SpS and 33.8 DS) and were the most impaired (ODI 51 vs. 42.3 SpS and 41.5 DS). IDH patients used more chiropractic treatment (42% vs. 33% SpS and 26% DS), had more Emergency Department (ED) visits (21% vs. 7% SpS and 4% DS), and used more opiate analgesics (49% vs. 29% SpS and 27% DS). After adjusting for age, gender, diagnosis, education, race, duration of symptoms, and compensation, Medicaid patients used significantly more opiate analgesics (58% Medicaid vs. 41% no insurance, 42% employer, 33% Medicare, and 32% private) and had more ED visits compared with other insurance types (31% Medicaid vs. 22% no insurance, 16% employer, 3% Medicare, and 11% private). IDH patients appear to have differences in sociodemographics, resource utilization, and functional impairment when compared with the SpS/DS patients. In addition, the differences in resource utilization for Medicaid patients may reflect differences in access to care. The data provided from these observational cohorts will serve as an important comparison to the SPORT randomized cohorts in the future.

A prospective study of fetal head growth, autistic traits and autism spectrum disorder.

PubMed

Blanken, Laura M E; Dass, Alena; Alvares, Gail; van der Ende, Jan; Schoemaker, Nikita K; El Marroun, Hanan; Hickey, Martha; Pennell, Craig; White, Scott; Maybery, Murray T; Dissanayake, Cheryl; Jaddoe, Vincent W V; Verhulst, Frank C; Tiemeier, Henning; McIntosh, Will; White, Tonya; Whitehouse, Andrew

2018-04-01

Altered trajectories of brain growth are often reported in Autism Spectrum Disorder (ASD), particularly during the first year of life. However, less is known about prenatal head growth trajectories, and no study has examined the relation with postnatal autistic symptom severity. The current study prospectively examined the association between fetal head growth and the spectrum of autistic symptom severity in two large population-based cohorts, including a sample of individuals with clinically diagnosed ASD. This study included 3,820 children from two longitudinal prenatal cohorts in The Netherlands and Australia, comprising 60 individuals with a confirmed diagnosis of ASD. Latent growth curve models were used to examine the relationship between fetal head circumference measured at three different time points and autistic traits measured in postnatal life using either the Social Responsiveness Scale or the Autism-Spectrum Quotient. While lower initial prenatal HC was weakly associated with increasing autistic traits in the Dutch cohort, this relationship was not observed in the Australian cohort, nor when the two cohorts were analysed together. No differences in prenatal head growth were found between individuals with ASD and controls. This large population-based study identified no consistent association across two cohorts between prenatal head growth and postnatal autistic traits. Our mixed findings suggest that further research in this area is needed. Autism Res 2018, 11: 602-612. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. It is not known whether different patterns of postnatal brain growth in Autism Spectrum Disorder (ASD) also occurs prenatally. We examined fetal head growth and autistic symptoms in two large groups from The Netherlands and Australia. Lower initial prenatal head circumference was associated with autistic traits in the Dutch, but not the Australian, group. No differences in head growth were found in individuals with ASD and controls when the data was combined. Our mixed findings suggest that more research in this area is needed. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc.

Social Origin and Graduation Age: A Cohort Comparison of Danish University Students

ERIC Educational Resources Information Center

Klausen, Trond Beldo

2016-01-01

This paper investigates whether social origin has an impact on graduation age among university students. A large number of social background factors are applied on a large data set of 4 successive cohorts of Danish university graduates born 1960-1975. These are cohorts for whom university attendance increased steeply. Contrary to recent findings…

Medication safety research by observational study design.

PubMed

Lao, Kim S J; Chui, Celine S L; Man, Kenneth K C; Lau, Wallis C Y; Chan, Esther W; Wong, Ian C K

2016-06-01

Observational studies have been recognised to be essential for investigating the safety profile of medications. Numerous observational studies have been conducted on the platform of large population databases, which provide adequate sample size and follow-up length to detect infrequent and/or delayed clinical outcomes. Cohort and case-control are well-accepted traditional methodologies for hypothesis testing, while within-individual study designs are developing and evolving, addressing previous known methodological limitations to reduce confounding and bias. Respective examples of observational studies of different study designs using medical databases are shown. Methodology characteristics, study assumptions, strengths and weaknesses of each method are discussed in this review.

Malignancy in Pediatric-onset Systemic Lupus Erythematosus.

PubMed

Bernatsky, Sasha; Clarke, Ann E; Zahedi Niaki, Omid; Labrecque, Jeremy; Schanberg, Laura E; Silverman, Earl D; Hayward, Kristen; Imundo, Lisa; Brunner, Hermine I; Haines, Kathleen A; Cron, Randy Q; Oen, Kiem; Wagner-Weiner, Linda; Rosenberg, Alan M; O'Neil, Kathleen M; Duffy, Ciarán M; von Scheven, Emily; Joseph, Lawrence; Lee, Jennifer L; Ramsey-Goldman, Rosalind

2017-10-01

To determine cancer incidence in a large pediatric-onset systemic lupus erythematosus (SLE) population. Data were examined from 12 pediatric SLE registries in North America. Patients were linked to their regional cancer registries to detect cancers observed after cohort entry, defined as date first seen in the clinic. The expected number of malignancies was obtained by multiplying the person-years in the cohort (defined from cohort entry to end of followup) by the geographically matched age-, sex-, and calendar year-specific cancer rates. The standardized incidence ratio (SIR; ratio of cancers observed to expected) was generated, with 95% CI. A total of 1168 patients were identified from the registries. The mean age at cohort entry was 13 years (SD 3.3), and 83.7% of the subjects were female. The mean duration of followup was 7.6 years, resulting in a total observation period of 8839 years spanning the calendar period 1974-2009. During followup, fourteen invasive cancers occurred (1.6 cancers per 1000 person-yrs, SIR 4.13, 95% CI 2.26-6.93). Three of these were hematologic (all lymphomas), resulting in an SIR for hematologic cancers of 4.68 (95% CI 0.96-13.67). SIR were increased for both male and female patients, and across age groups. Although cancer remains a relatively rare outcome in pediatric-onset SLE, our data do suggest an increase in cancer for patients followed an average of 7.6 years. About one-fifth of the cancers were hematologic. Longer followup, and study of drug effects and disease activity, is warranted.

Cohort profile: LIFEWORK, a prospective cohort study on occupational and environmental risk factors and health in the Netherlands.

PubMed

Reedijk, Marije; Lenters, Virissa; Slottje, Pauline; Pijpe, Anouk; Peeters, Petra H; Korevaar, Joke C; Bueno-de-Mesquita, Bas; Verschuren, W M Monique; Verheij, Robert A; Pieterson, Inka; van Leeuwen, Flora E; Rookus, Matti A; Kromhout, Hans; Vermeulen, Roel C H

2018-02-03

LIFEWORK is a large federated prospective cohort established in the Netherlands to quantify the health effects of occupational and environmental exposures. This cohort is also the Dutch contribution to the international Cohort Study of Mobile Phone Use and Health (COSMOS). In this paper, we describe the study design, ongoing data collection, baseline characteristics of participants and the repeatability of key questionnaire items. 88 466 participants were enrolled in three cohort studies in 2011-2012. Exposure information was collected by a harmonised core questionnaire, or modelled based on occupational and residential histories; domains include air pollution (eg, nitrogen dioxide (NO 2 ), particulate matter with diameter ≤2.5 µm (PM 2.5 )), noise, electromagnetic fields (EMF), mobile phone use, shift work and occupational chemical exposures. Chronic and subacute health outcomes are assessed by self-report and through linkage with health registries. Participants had a median age of 51 years at baseline (range 19-87), and the majority are female (90%), with nurses being over-represented. Median exposure levels of NO 2 , PM 2.5 , EMF from base stations and noise at the participants' home addresses at baseline were 22.9 µg/m 3 , 16.6 µg/m 3 , 0.003 mWm 2 and 53.1 dB, respectively. Twenty-two per cent of participants reported to have started using a mobile phone more than 10 years prior to baseline. Repeatability for self-reported exposures was moderate to high (weighted kappa range: 0.69-1) for a subset of participants (n=237) who completed the questionnaire twice. We are actively and passively observing participants; we plan to administer a follow-up questionnaire every 4-5 years-the first follow-up will be completed in 2018-and linkage to cause-of-death and cancer registries occurs on a (bi)annual basis. This prospective cohort offers a unique, large and rich resource for research on contemporary occupational and environmental health risks and will contribute to the large international COSMOS study on mobile phone use and health. © 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.

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.

Prospective validation of pathologic complete response models in rectal cancer: Transferability and reproducibility.

PubMed

van Soest, Johan; Meldolesi, Elisa; van Stiphout, Ruud; Gatta, Roberto; Damiani, Andrea; Valentini, Vincenzo; Lambin, Philippe; Dekker, Andre

2017-09-01

Multiple models have been developed to predict pathologic complete response (pCR) in locally advanced rectal cancer patients. Unfortunately, validation of these models normally omit the implications of cohort differences on prediction model performance. In this work, we will perform a prospective validation of three pCR models, including information whether this validation will target transferability or reproducibility (cohort differences) of the given models. We applied a novel methodology, the cohort differences model, to predict whether a patient belongs to the training or to the validation cohort. If the cohort differences model performs well, it would suggest a large difference in cohort characteristics meaning we would validate the transferability of the model rather than reproducibility. We tested our method in a prospective validation of three existing models for pCR prediction in 154 patients. Our results showed a large difference between training and validation cohort for one of the three tested models [Area under the Receiver Operating Curve (AUC) cohort differences model: 0.85], signaling the validation leans towards transferability. Two out of three models had a lower AUC for validation (0.66 and 0.58), one model showed a higher AUC in the validation cohort (0.70). We have successfully applied a new methodology in the validation of three prediction models, which allows us to indicate if a validation targeted transferability (large differences between training/validation cohort) or reproducibility (small cohort differences). © 2017 American Association of Physicists in Medicine.

[Individual linkage of primary data with secondary and registry data within large cohort studies - capabilities and procedural proposals].

PubMed

Stallmann, C; Ahrens, W; Kaaks, R; Pigeot, I; Swart, E; Jacobs, S

2015-02-01

Some German cohort studies have already linked secondary and registry data with primary data from interviews and medical examinations. This offers the opportunity to obtain more valid information by taking advantage of the strengths of these data synergistically and overcome their individual weaknesses at the same time. The potential and the requirements for linking secondary and registry data with primary data from cohort studies is described generally and illustrated by the example of the "German National Cohort" (GNC). The transfer and usage of secondary and registry data require that administrative and logistic efforts be made over the whole study period. In addition, rigid data protection regulations for using social data have to be observed. The particular strengths of secondary and registry data, namely their objectivity and independence from recall bias, add to the strengths of newly collected primary data and improve the assessment of morbidity endpoints, exposure history and need of patient care. Moreover, new insights on quality and on the added value of linking different data sources may be obtained. © Georg Thieme Verlag KG Stuttgart · New York.

Increased risk of pyogenic liver abscess in patients with alcohol intoxication: A population-based retrospective cohort study.

PubMed

Wang, Yao-Chien; Yang, Kai-Wei; Lee, Tien-Ying Peter; Lin, Cheng-Li; Liaw, Geng-Wang; Hung, Dong-Zong; Kao, Chia-Hung; Chen, Wei-Kung; Yang, Tse-Yen

2017-11-01

We designed a population-based retrospective cohort study to investigate the association between the event of alcohol intoxication and the risk of pyogenic liver abscess. The present study enrolled 245,076 patients with a history of alcohol intoxication from 2000 to 2010 and matched each of them with four comparison patients, with similar mean age and sex ratios. We determined the cumulative incidences and adjusted hazard ratios (aHRs) of liver abscess. A significant association was observed between alcohol intoxication and liver abscess. The incidence density rate of liver abscess was 3.47-fold greater in the alcohol intoxication (AI) cohort than in the non-AI cohort (12.2 vs. 3.43 per 10,000 person-years), with an adjusted HR (aHR) of 2.64 (95% CI = 2.26 to 3.08). This population-based study positively associated the event of alcohol intoxication with increased risk of liver abscess. Our findings warrant further large-scale and in-depth investigations in this area. Copyright © 2017 Elsevier Inc. All rights reserved.

Exploring educational disparities in risk of preterm delivery: a comparative study of 12 European birth cohorts.

PubMed

Poulsen, Gry; Strandberg-Larsen, Katrine; Mortensen, Laust; Barros, Henrique; Cordier, Sylvaine; Correia, Sofia; Danileviciute, Asta; van Eijsden, Manon; Fernández-Somoano, Ana; Gehring, Ulrike; Grazuleviciene, Regina; Hafkamp-de Groen, Esther; Henriksen, Tine Brink; Jensen, Morten Søndergaard; Larrañaga, Isabel; Magnus, Per; Pickett, Kate; Raat, Hein; Richiardi, Lorenzo; Rouget, Florence; Rusconi, Franca; Stoltenberg, Camilla; Uphoff, Eleonora P; Vrijkotte, Tanja G M; Wijga, Alet H; Vrijheid, Martine; Osler, Merete; Andersen, Anne-Marie Nybo

2015-05-01

An association between education and preterm delivery has been observed in populations across Europe, but differences in methodology limit comparability. We performed a direct cross-cohort comparison of educational disparities in preterm delivery based on individual-level birth cohort data. The study included data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal, and Spain. The cohorts included between 2434 and 99 655 pregnancies. The association between maternal education and preterm delivery (22-36 completed weeks of gestation) was reported as risk ratios, risk differences, and slope indexes of inequality with 95% confidence intervals (CIs). Singleton preterm live delivery proportion varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and maternal characteristics. Nevertheless, there were similar educational differences in risk of preterm delivery in 8 of the 12 cohorts with slope index of inequality varying between 2.2 [95% CI 1.1, 3.3] and 4.0 [95% CI 1.4, 6.6] excess preterm deliveries per 100 singleton deliveries among the educationally most disadvantaged, and risk ratio between the lowest and highest education category varying from 1.4 [95% CI 1.1, 1.8] to 1.9 [95% CI 1.2, 3.1]. No associations were found in the last four cohorts. Educational disparities in preterm delivery were found all over Europe. Despite differences in the distributions of education and preterm delivery, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics did not explain the differences. © 2015 John Wiley & Sons Ltd.

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.

XLID-Causing Mutations and Associated Genes Challenged in Light of Data From Large-Scale Human Exome Sequencing

PubMed Central

Piton, Amélie; Redin, Claire; Mandel, Jean-Louis

2013-01-01

Because of the unbalanced sex ratio (1.3–1.4 to 1) observed in intellectual disability (ID) and the identification of large ID-affected families showing X-linked segregation, much attention has been focused on the genetics of X-linked ID (XLID). Mutations causing monogenic XLID have now been reported in over 100 genes, most of which are commonly included in XLID diagnostic gene panels. Nonetheless, the boundary between true mutations and rare non-disease-causing variants often remains elusive. The sequencing of a large number of control X chromosomes, required for avoiding false-positive results, was not systematically possible in the past. Such information is now available thanks to large-scale sequencing projects such as the National Heart, Lung, and Blood (NHLBI) Exome Sequencing Project, which provides variation information on 10,563 X chromosomes from the general population. We used this NHLBI cohort to systematically reassess the implication of 106 genes proposed to be involved in monogenic forms of XLID. We particularly question the implication in XLID of ten of them (AGTR2, MAGT1, ZNF674, SRPX2, ATP6AP2, ARHGEF6, NXF5, ZCCHC12, ZNF41, and ZNF81), in which truncating variants or previously published mutations are observed at a relatively high frequency within this cohort. We also highlight 15 other genes (CCDC22, CLIC2, CNKSR2, FRMPD4, HCFC1, IGBP1, KIAA2022, KLF8, MAOA, NAA10, NLGN3, RPL10, SHROOM4, ZDHHC15, and ZNF261) for which replication studies are warranted. We propose that similar reassessment of reported mutations (and genes) with the use of data from large-scale human exome sequencing would be relevant for a wide range of other genetic diseases. PMID:23871722

Intralesional Osteophyte Regrowth Following Autologous Chondrocyte Implantation after Previous Treatment with Marrow Stimulation Technique.

PubMed

Demange, Marco Kawamura; Minas, Tom; von Keudell, Arvind; Sodha, Sonal; Bryant, Tim; Gomoll, Andreas H

2017-04-01

Objective Bone marrow stimulation surgeries are frequent in the treatment of cartilage lesions. Autologous chondrocyte implantation (ACI) may be performed after failed microfracture surgery. Alterations to subchondral bone as intralesional osteophytes are commonly seen after previous microfracture and removed during ACI. There have been no reports on potential recurrence. Our purpose was to evaluate the incidence of intralesional osteophyte development in 2 cohorts: existing intralesional osteophytes and without intralesional osteophytes at the time of ACI. Study Design We identified 87 patients (157 lesions) with intralesional osteophytes among a cohort of 497 ACI patients. Osteophyte regrowth was analyzed on magnetic resonance imaging and categorized as small or large (less or more than 50% of the cartilage thickness). Twenty patients (24 defects) without intralesional osteophytes at the time of ACI acted as control. Results Osteophyte regrowth was observed in 39.5% of lesions (34.4% of small osteophytes and 5.1% of large osteophytes). In subgroup analyses, regrowth was observed in 45.8% of periosteal-covered defects and in 18.9% of collagen membrane-covered defects. Large osteophyte regrowth occurred in less than 5% in either group. Periosteal defects showed a significantly higher incidence for regrowth of small osteophytes. In the control group, intralesional osteophytes developed in 16.7% of the lesions. Conclusions Even though intralesional osteophytes may regrow after removal during ACI, most of them are small. Small osteophyte regrowth occurs almost twice in periosteum-covered ACI. Large osteophytes occur only in 5% of patients. Intralesional osteophyte formation is not significantly different in preexisting intralesional osteophytes and control groups.

Intralesional Osteophyte Regrowth Following Autologous Chondrocyte Implantation after Previous Treatment with Marrow Stimulation Technique

PubMed Central

Demange, Marco Kawamura; Minas, Tom; von Keudell, Arvind; Sodha, Sonal; Bryant, Tim; Gomoll, Andreas H.

2016-01-01

Objective Bone marrow stimulation surgeries are frequent in the treatment of cartilage lesions. Autologous chondrocyte implantation (ACI) may be performed after failed microfracture surgery. Alterations to subchondral bone as intralesional osteophytes are commonly seen after previous microfracture and removed during ACI. There have been no reports on potential recurrence. Our purpose was to evaluate the incidence of intralesional osteophyte development in 2 cohorts: existing intralesional osteophytes and without intralesional osteophytes at the time of ACI. Study Design We identified 87 patients (157 lesions) with intralesional osteophytes among a cohort of 497 ACI patients. Osteophyte regrowth was analyzed on magnetic resonance imaging and categorized as small or large (less or more than 50% of the cartilage thickness). Twenty patients (24 defects) without intralesional osteophytes at the time of ACI acted as control. Results Osteophyte regrowth was observed in 39.5% of lesions (34.4% of small osteophytes and 5.1% of large osteophytes). In subgroup analyses, regrowth was observed in 45.8% of periosteal-covered defects and in 18.9% of collagen membrane–covered defects. Large osteophyte regrowth occurred in less than 5% in either group. Periosteal defects showed a significantly higher incidence for regrowth of small osteophytes. In the control group, intralesional osteophytes developed in 16.7% of the lesions. Conclusions Even though intralesional osteophytes may regrow after removal during ACI, most of them are small. Small osteophyte regrowth occurs almost twice in periosteum-covered ACI. Large osteophytes occur only in 5% of patients. Intralesional osteophyte formation is not significantly different in preexisting intralesional osteophytes and control groups. PMID:28345403

Health Assessment Questionnaire disability progression in early rheumatoid arthritis: Systematic review and analysis of two inception cohorts

PubMed Central

Norton, Sam; Fu, Bo; Scott, David L.; Deighton, Chris; Symmons, Deborah P.M.; Wailoo, Allan J.; Tosh, Jonathan; Lunt, Mark; Davies, Rebecca; Young, Adam; Verstappen, Suzanne M.M

2014-01-01

Objective The Health Assessment Questionnaire is widely used for patients with inflammatory polyarthritis (IP) and its subset, rheumatoid arthritis (RA). In this study, we evaluated the progression of HAQ scores in RA (i) by systematically reviewing the published literature on the methods used to assess changes in functional disability over time and (ii) to study in detail HAQ progression in two large prospective observational studies from the UK. Methods Data from two large inception cohorts, ERAS and NOAR, were studied to determine trajectories of HAQ progression over time by applying latent class growth models (LCGMs) to each dataset separately. Age, sex, baseline DAS28, symptom duration, rheumatoid factor, fulfilment of the 1987 ACR criteria and socio-economic status (SES) were included as potential predictors of HAQ trajectory subgroup membership. Results The literature search identified 49 studies showing that HAQ progression has mainly been based on average changes in the total study population. In the HAQ progression study, a LCGM with four HAQ trajectory subgroups was selected as providing the best fit in both cohorts. In both the cohorts, older age, female sex, longer symptom duration, fulfilment of the 1987 ACR criteria, higher DAS28 and lower SES were associated with increased likelihood of membership of subgroups with worse HAQ progression. Conclusion Four distinct HAQ trajectory subgroups were derived from the ERAS and NOAR cohorts. The fact that the subgroups identified were nearly identical supports their validity. Identifying distinct groups of patients who are at risk of poor functional outcome may help to target therapy to those who are most likely to benefit. PMID:24925692

Characteristics and provision of care of patients with the acute respiratory distress syndrome: descriptive findings from the DACAPO cohort baseline and comparison with international findings

PubMed Central

Brandstetter, Susanne; Brandl, Magdalena; Blecha, Sebastian; Quintel, Michael; Weber-Carstens, Steffen; Kluge, Stefan; Meybohm, Patrick; Rolfes, Caroline; Ellger, Björn; Bach, Friedhelm; Welte, Tobias; Muders, Thomas; Thomann-Hackner, Kathrin; Bein, Thomas; Apfelbacher, Christian

2017-01-01

Background Little is known about the characteristics and real world life circumstances of ARDS (acute respiratory distress syndrome) patient populations. This knowledge is essential for transferring evidence-based therapy into routine healthcare. The aim of this study was to report socio-demographic and clinical characteristics in an unselected population of ARDS patients and to compare these results to findings from other large ARDS cohorts. Methods A German based cross-sectional observational study was carried out. A total of 700 ARDS patients were recruited in 59 study sites between September 2014 and January 2016. Socio-demographic, disease and care related variables were recorded. Additionally, characteristics of other large ARDS cohorts identified by a systematic literature search were extracted into evidence tables. Results Median age of ARDS patients was 58 years, 69% were male. Sixty percent had no employment, predominantly due to retirement. Seventy-one percent lived with a partner. The main cause of ARDS was a pulmonary ‘direct’ origin (79%). The distribution of severity was as follows: mild (14%), moderate (48%), severe (38%). Overall ICU mortality was calculated to be 34%. The observed prevalence of critical events (hypoxemia, hypoglycemia, re-intubation) was 47%. Supportive measures during ICU-treatment were applied to 60% of the patients. Other ARDS cohorts revealed a high heterogeneity in reported concomitant diseases, but sepsis and pneumonia were most frequently reported. Mean age ranged from 54 to 71 years and most patients were male. Other socio-demographic factors have been almost neglected. Conclusions The proportion of patients suffering of mild ARDS was lower compared to the only study identified, which also applied the Berlin definition. The frequency of critical events during ICU treatment was high and the implementation of evidence-based therapy (prone positioning, neuro-muscular blockers) was limited. More evidence on socio-demographic characteristics and further studies applying the current diagnostic criteria are desirable. PMID:28449491

Pregnancy outcomes following exposure to efavirenz-based antiretroviral therapy in the Republic of Congo.

PubMed

Bisio, Francesca; Nicco, Elena; Calzi, Anna; Giacobbe, Daniele Roberto; Mesini, Alessio; Banguissa, Hubert; Vividila, Nicole Edith; Mahoungou, Pélagie; Boumba, Jean Denis; Mboungou, Franc Astyanax Mayinda; Bruzzone, Bianca; Ratto, Sandra; Icardi, Giancarlo; Viscoli, Claudio; Bruzzi, Paolo

2015-04-01

WHO recently recommended efavirenz (EFV) use for HIV infection through pregnancy, breastfeeding and childbearing age. However the use of EFV during pregnancy remains of concern and not all national guidelines reflect WHO advice. Few data are available concerning pregnancy outcomes. The objective of our study was to evaluate pregnancy outcomes in a cohort of women who conceived on EFV. A retrospective, multicenter cohort study was conducted in Pointe Noire, Republic of Congo (September 2005- June 2012). The following adverse pregnancy outcomes were considered: births defects, low birth weight, premature delivery, stillbirth and abortion, stratified by antiretroviral exposure at the time of conception. During the study period, 188 women conceived on antiretrovirals: 35 (18.6%) on EFV-based regimens and 153 (81.4%) on nevirapine-based regimens. Adverse pregnancy outcomes were observed in 17/35 (48.6%, 95% CI 33.0-64.4%) women in the EFV group and in 43/153 (28.1%, 95% CI 21.6-35.7%) in the non-EFV group (p=0.019). No birth defect was observed in either group. An increased incidence of adverse pregnancy outcomes was observed in the EFV group. As WHO is promoting a widespread use of EFV also for women in childbearing age, our study emphasizes the importance of launching large prospective cohort studies investigating pregnancy outcomes in exposed women.

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.

NCI Cohort Consortium Membership

Cancer.gov

The NCI Cohort Consortium membership is international and includes investigators responsible for more than 40 high-quality cohorts who are studying large and diverse populations in more than 15 different countries.

NCI Cohort Consortium

Cancer.gov

The NCI Cohort Consortium is an extramural-intramural partnership formed by the National Cancer Institute to address the need for large-scale collaborations to pool the large quantity of data and biospecimens necessary to conduct a wide range of cancer studies.

Permanent neonatal diabetes: different aetiology in Arabs compared to Europeans.

PubMed

Habeb, Abdelhadi M; Flanagan, Sarah E; Deeb, Asma; Al-Alwan, Ibrahim; Alawneh, Hussain; Balafrej, Angham A L; Mutair, Angam; Hattersley, Andrew T; Hussain, Khalid; Ellard, Sian

2012-08-01

Mutations in the KCNJ11 and ABCC8 genes that encode the pancreatic K(ATP) channel are the commonest cause of permanent neonatal diabetes mellitus (PNDM). The authors aimed to define the genetic causes of PNDM in a large cohort of Arab patients and compare them with a British cohort tested in the same laboratory. Retrospective observational study. International genetics centre. Arab and British subjects with PNDM who were referred for genetic testing over the same period. Comparison of genotypes and phenotypes between the two cohorts. The aetiology and phenotype of PNDM in an Arab compared to a British cohort. 88 Arab and 77 British probands were referred between 2006 and 2011, inclusive. Consanguinity was higher among Arabs (63.6% vs 10.4%) and a higher percentage had a genetic diagnosis compared to the British cohort (63.6% vs 41.6%). Recessive EIF2AK3 gene mutations were the commonest cause of PNDM in the Arab cohort (22.7%) followed by INS (12.5%), and KCNJ11 and GCK (5.7% each), whereas K(ATP) channel mutations were the commonest cause (29.9%) in the British cohort. In 37.5% of Arab patients PNDM was part of a genetic syndrome compared to 7.8% of the British cohort. PNDM in the Arab population has a different genetic spectrum compared to British patients where KATP channel mutations are the commonest cause, similar to other European populations. In Arabs, PNDM is more likely to be part of a recessively inherited syndrome, possibly due to the higher rate of consanguinity.

Responsiveness-informed multiple imputation and inverse probability-weighting in cohort studies with missing data that are non-monotone or not missing at random.

PubMed

Doidge, James C

2018-02-01

Population-based cohort studies are invaluable to health research because of the breadth of data collection over time, and the representativeness of their samples. However, they are especially prone to missing data, which can compromise the validity of analyses when data are not missing at random. Having many waves of data collection presents opportunity for participants' responsiveness to be observed over time, which may be informative about missing data mechanisms and thus useful as an auxiliary variable. Modern approaches to handling missing data such as multiple imputation and maximum likelihood can be difficult to implement with the large numbers of auxiliary variables and large amounts of non-monotone missing data that occur in cohort studies. Inverse probability-weighting can be easier to implement but conventional wisdom has stated that it cannot be applied to non-monotone missing data. This paper describes two methods of applying inverse probability-weighting to non-monotone missing data, and explores the potential value of including measures of responsiveness in either inverse probability-weighting or multiple imputation. Simulation studies are used to compare methods and demonstrate that responsiveness in longitudinal studies can be used to mitigate bias induced by missing data, even when data are not missing at random.

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.

Splenic marginal zone lymphoma: excellent outcomes in 64 patients treated in the rituximab era.

PubMed

Starr, Adam G; Caimi, Paolo F; Fu, PingFu; Massoud, Mira R; Meyerson, Howard; Hsi, Eric D; Mansur, David B; Cherian, Sheen; Cooper, Brenda W; De Lima, Marcos J G; Lazarus, Hillard M; Gerson, Stanton L; Jagadeesh, Deepa; Smith, Mitchell R; Dean, Robert M; Pohlman, Brad L; Hill, Brian T; William, Basem M

2017-08-01

Splenic marginal zone lymphoma (SMZL) is a rare non-Hodgkin lymphoma. We sought to identify prognostic factors and define outcomes in a cohort of 64 patients with SMZL who were treated at two large academic medical centers in North America in the rituximab era. Over a median follow-up of 37.8 (range 6-167.1) months, Kaplan-Meier estimate of median OS was 156.3 months and median PFS was 52.9 months. On univariate analysis, baseline hemoglobin <12 g/dl was associated with inferior OS (p = 0.045). High-risk FLIPI score was associated with inferior PFS when compared with intermediate/low risk (p = 0.05) and marginally significant with regard to OS (p = 0.056). Splenectomy was not predictive of OS or PFS (p = 0.563 and 0.937, respectively). Transformation to diffuse large B-cell lymphoma occurred in four (6.3%) patients during the observation period. OS was comparable to contemporaneous cohorts of patients with extranodal and nodal marginal lymphomas and FLIPI score was highly predictive for inferior PFS and OS when all three cohorts were analyzed together. Outcomes of SMZL, in our series, were excellent, with a median OS of >13 years. Low hemoglobin and high-risk FLIPI were associated with inferior outcomes.

Investigation of Multiple Susceptibility Loci for Inflammatory Bowel Disease in an Italian Cohort of Patients

PubMed Central

Latiano, Anna; Palmieri, Orazio; Latiano, Tiziana; Corritore, Giuseppe; Bossa, Fabrizio; Martino, Giuseppina; Biscaglia, Giuseppe; Scimeca, Daniela; Valvano, Maria Rosa; Pastore, Maria; Marseglia, Antonio; D'Incà, Renata; Andriulli, Angelo; Annese, Vito

2011-01-01

Background Recent GWAs and meta-analyses have outlined about 100 susceptibility genes/loci for inflammatory bowel diseases (IBD). In this study we aimed to investigate the influence of SNPs tagging the genes/loci PTGER4, TNFSF15, NKX2-3, ZNF365, IFNG, PTPN2, PSMG1, and HLA in a large pediatric- and adult-onset IBD Italian cohort. Methods Eight SNPs were assessed in 1,070 Crohn's disease (CD), 1,213 ulcerative colitis (UC), 557 of whom being diagnosed at the age of ≤16 years, and 789 healthy controls. Correlations with sub-phenotypes and major variants of NOD2 gene were investigated. Results The SNPs tagging the TNFSF15, NKX2-3, ZNF365, and PTPN2 genes were associated with CD (P values ranging from 0.037 to 7×10−6). The SNPs tagging the PTGER4, NKX2-3, ZNF365, IFNG, PSMG1, and HLA area were associated with UC (P values 0.047 to 4×10−5). In the pediatric cohort the associations of TNFSF15, NKX2-3 with CD, and PTGER4, NKX2-3, ZNF365, IFNG, PSMG1 with UC, were confirmed. Association with TNFSF15 and pediatric UC was also reported. A correlation with NKX2-3 and need for surgery (P  =  0.038), and with HLA and steroid-responsiveness (P  =  0.024) in UC patients was observed. Moreover, significant association in our CD cohort with TNFSF15 SNP and colonic involvement (P  =  0.021), and with ZNF365 and ileal location (P  =  0.024) was demonstrated. Conclusions We confirmed in a large Italian cohort the associations with CD and UC of newly identified genes, both in adult and pediatric cohort of patients, with some influence on sub-phenotypes. PMID:21818367

International Childhood Cancer Cohort Consortium

Cancer.gov

An alliance of several large-scale prospective cohort studies of children to pool data and biospecimens from individual cohorts to study various modifiable and genetic factors in relation to cancer risk

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

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.

Prescription patterns in asthma patients initiating salmeterol in UK general practice: a retrospective cohort study using the General Practice Research Database (GPRD).

PubMed

DiSantostefano, Rachael L; Davis, Kourtney J

2011-06-01

An association between salmeterol, a long-acting β(2)-agonist (LABA), use and rare serious asthma events or asthma mortality was observed in two large clinical trials. This has resulted in heightened scrutiny of LABAs and comprehensive reviews by regulatory agencies. The aim of this retrospective observational cohort study was to better characterize salmeterol medication use patterns in the UK. We describe asthma prescription patterns in a cohort of patients (n =17,745) in the General Practice Research Database who initiated treatment with salmeterol-containing prescriptions between 2003 and 2006, including salmeterol and salmeterol/fluticasone propionate in a single device. Prescriptions patterns by medication class, including concurrent prescription of salmeterol with inhaled corticosteroids (ICS), were described using 6-month intervals in the 1-year period before and after the salmeterol-containing index prescription. In the 0- to 6-month and 7- to 12-month periods prior to initiation of the salmeterol-containing prescription, the cohort experienced worsening of asthma, measured by an increase in the proportion of patients with prescriptions for short-acting β-agonists [SABA] (73-89%), ICS (70-81%) and systemic corticosteroids (14-28%). Nearly all patients prescribed salmeterol were concurrently prescribed ICS (≥95% within 90 days). In the 12 months following initiation of the salmeterol-containing prescription, a decrease in asthma prescriptions was observed. These results support the appropriate prescribing of salmeterol-containing medications, as per recommendations in asthma treatment guidelines in the UK. Salmeterol was consistently prescribed as an add-on asthma-controller with an ICS for most patients, and was associated with improvements in asthma control, as indicated by decreases in SABA and systemic corticosteroid prescriptions following salmeterol introduction.

Design and implementation of the canadian kidney disease cohort study (CKDCS): A prospective observational study of incident hemodialysis patients

PubMed Central

2011-01-01

Background Many nephrology observational studies use renal registries, which have well known limitations. The Canadian Kidney Disease Cohort Study (CKDCS) is a large prospective observational study of patients commencing hemodialysis in five Canadian centers. This study focuses on delineating potentially reversible determinants of adverse outcomes that occur in patients receiving dialysis for end-stage renal disease (ESRD). Methods/Design The CKDCS collects information on risk factors and outcomes, and stores specimens (blood, dialysate, hair and fingernails) at baseline and in long-term follow-up. Such specimens will permit measurements of biochemical markers, proteomic and genetic parameters (proteins and DNA) not measured in routine care. To avoid selection bias, all consenting incident hemodialysis patients at participating centers are enrolled, the large sample size (target of 1500 patients), large number of exposures, and high event rates will permit the exploration of multiple potential research questions. Preliminary Results Data on the baseline characteristics from the first 1074 subjects showed that the average age of patients was 62 (range; 50-73) years. The leading cause of ESRD was diabetic nephropathy (41.9%), and the majority of the patients were white (80.0%). Only 18.7% of the subjects received dialysis in a satellite unit, and over 80% lived within a 50 km radius of the nearest nephrologist's practice. Discussion The prospective design, detailed clinical information, and stored biological specimens provide a wealth of information with potential to greatly enhance our understanding of risk factors for adverse outcomes in dialysis patients. The scientific value of the stored patient tissue will grow as new genetic and biochemical markers are discovered in the future. PMID:21324196

Associations between otitis media and child behavioural and learning difficulties: Results from a Danish cohort.

PubMed

Niclasen, J; Obel, C; Homøe, P; Kørvel-Hanquist, A; Dammeyer, J

2016-05-01

Findings from studies investigating early childhood episodes of otitis media (OM) and developmental outcomes are inconclusive. This may in part be because large-scale prospective studies controlling for relevant confounding factors are sparse. The present study investigates associations between OM in early childhood and later behavioural and learning difficulties controlling for relevant confounding factors. The study applied data from the Aarhus Birth Cohort's 10-12-year-old follow-up (N=7578). Associations between retrospective parent-reported OM (no OM; 1-3 episodes of OM with/without tympanostomy tubes; 4+ OM episodes without tympanostomy tubes and; 4+ OM episodes with tympanostomy tubes) one the one hand, and parent- and teacher-reported scores on the Strengths and Difficulties Questionnaire (SDQ) and parent-reported academic difficulties on the other hand, were investigated. The following variables were controlled for: parental educational level, maternal and paternal school problems, parental post-natal smoking, breastfeeding, and age at which the child started walking. All analyses were stratified by gender. Large differences in background characteristics were observed for the group of children with 4+ OM episodes with tympanostomy tubes compared to the no OM group. After controlling for relevant confounders, negative associations were consistently observed for the group of children with 4+ episodes of OM with tympanostomy tubes compared to the group of children without OM. This was particularly so for girls. The findings suggest an association between 4+ episodes of early OM with tympanostomy tubes and behavioural and learning difficulties later in childhood. The large inter-group differences, i.e. impact of residual and unmeasured confounding factors, may in part explain the observed associations and underline the need to include these in future studies. Copyright © 2016. Published by Elsevier Ireland Ltd.

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

Enhancing Large-Class Teaching: A Systematic Comparison of Rich-Media Materials

ERIC Educational Resources Information Center

Saunders, F. C.; Hutt, I.

2015-01-01

Large cohorts (>200 students) are an ever-increasing presence in the UK higher education (HE) sector. Providing excellent teaching and learning to these large classes is an ongoing challenge for teaching faculty, a challenge intensified when the cohort comprises 85% non-native English speakers. This paper presents the findings of a project to…

Fine Particulate Matter (PM2.5) and the Risk of Stroke in the REGARDS Cohort.

PubMed

McClure, Leslie A; Loop, Matthew S; Crosson, William; Kleindorfer, Dawn; Kissela, Brett; Al-Hamdan, Mohammad

2017-08-01

Ambient particulate matter has been shown to be associated with declining human health, although the association between fine particulate matter (PM 2.5 ) and stroke is uncertain. We utilized satellite-derived measures of PM 2.5 to examine the association between exposure and stroke in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. We used a time-stratified case-crossover design, with exposure lags of 1 day, 2 days, and 3 days. We examined all strokes, as well as ischemic and hemorrhagic strokes separately. Among 30,239 participants in the REGARDS study, 746 incident events were observed: 72 hemorrhagic, 617 ischemic, and 57 of unknown type. Participants exposed to higher levels of PM 2.5 more often resided in urban areas compared to rural, and in the southeastern United States. After adjustment for temperature and relative humidity, no association was observed between PM 2.5 exposure and stroke, regardless of the lag (1-day lag OR = .99, 95% CI: .83-1.19; 2-day lag OR = .95, 95% CI: .80-1.14; 3-day lag OR = .95, 95% CI = .79-1.13). Similar results were observed for the stroke subtypes. In this large cohort of African-Americans and whites, no association was observed between PM 2.5 and stroke. The ability to examine this association with a large number of outcomes and by stroke subtype helps fill a gap in the literature examining the association between PM 2.5 and stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Creating a Common Data Model for Comparative Effectiveness with the Observational Medical Outcomes Partnership.

PubMed

FitzHenry, F; Resnic, F S; Robbins, S L; Denton, J; Nookala, L; Meeker, D; Ohno-Machado, L; Matheny, M E

2015-01-01

Adoption of a common data model across health systems is a key infrastructure requirement to allow large scale distributed comparative effectiveness analyses. There are a growing number of common data models (CDM), such as Mini-Sentinel, and the Observational Medical Outcomes Partnership (OMOP) CDMs. In this case study, we describe the challenges and opportunities of a study specific use of the OMOP CDM by two health systems and describe three comparative effectiveness use cases developed from the CDM. The project transformed two health system databases (using crosswalks provided) into the OMOP CDM. Cohorts were developed from the transformed CDMs for three comparative effectiveness use case examples. Administrative/billing, demographic, order history, medication, and laboratory were included in the CDM transformation and cohort development rules. Record counts per person month are presented for the eligible cohorts, highlighting differences between the civilian and federal datasets, e.g. the federal data set had more outpatient visits per person month (6.44 vs. 2.05 per person month). The count of medications per person month reflected the fact that one system's medications were extracted from orders while the other system had pharmacy fills and medication administration records. The federal system also had a higher prevalence of the conditions in all three use cases. Both systems required manual coding of some types of data to convert to the CDM. The data transformation to the CDM was time consuming and resources required were substantial, beyond requirements for collecting native source data. The need to manually code subsets of data limited the conversion. However, once the native data was converted to the CDM, both systems were then able to use the same queries to identify cohorts. Thus, the CDM minimized the effort to develop cohorts and analyze the results across the sites.

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.

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

PubMed

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

2014-08-01

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

Observational methods to assess the effectiveness of screening colonoscopy in reducing right colon cancer mortality risk: SCOLAR.

PubMed

Goodman, Michael; Fletcher, Robert H; Doria-Rose, V Paul; Jensen, Christopher D; Zebrowski, Alexis M; Becerra, Tracy A; Quinn, Virginia P; Zauber, Ann G; Corley, Douglas A; Doubeni, Chyke A

2015-11-01

Screening colonoscopy's effectiveness in reducing risk of death from right colon cancers remains unclear. Methodological challenges of existing observational studies addressing this issue motivated the design of 'Effectiveness of Screening for Colorectal Cancer in Average-Risk Adults (SCOLAR)'. SCOLAR is a nested case-control study based on two large integrated health systems. This affords access to a large, well-defined historical cohort linked to integrated data on cancer outcomes, patient eligibility, test indications and important confounders. We found electronic data adequate for excluding ineligible patients (except family history), but not the detailed information needed for test indication assignment. The lessons of SCOLAR's design and implementation may be useful for future studies seeking to evaluate the effectiveness of screening tests in community settings.

The Cancer Epidemiology Descriptive Cohort Database: A Tool to Support Population-Based Interdisciplinary Research

PubMed Central

Kennedy, Amy E.; Khoury, Muin J.; Ioannidis, John P.A.; Brotzman, Michelle; Miller, Amy; Lane, Crystal; Lai, Gabriel Y.; Rogers, Scott D.; Harvey, Chinonye; Elena, Joanne W.; Seminara, Daniela

2017-01-01

Background We report on the establishment of a web-based Cancer Epidemiology Descriptive Cohort Database (CEDCD). The CEDCD’s goals are to enhance awareness of resources, facilitate interdisciplinary research collaborations, and support existing cohorts for the study of cancer-related outcomes. Methods Comprehensive descriptive data were collected from large cohorts established to study cancer as primary outcome using a newly developed questionnaire. These included an inventory of baseline and follow-up data, biospecimens, genomics, policies, and protocols. Additional descriptive data extracted from publicly available sources were also collected. This information was entered in a searchable and publicly accessible database. We summarized the descriptive data across cohorts and reported the characteristics of this resource. Results As of December 2015, the CEDCD includes data from 46 cohorts representing more than 6.5 million individuals (29% ethnic/racial minorities). Overall, 78% of the cohorts have collected blood at least once, 57% at multiple time points, and 46% collected tissue samples. Genotyping has been performed by 67% of the cohorts, while 46% have performed whole-genome or exome sequencing in subsets of enrolled individuals. Information on medical conditions other than cancer has been collected in more than 50% of the cohorts. More than 600,000 incident cancer cases and more than 40,000 prevalent cases are reported, with 24 cancer sites represented. Conclusions The CEDCD assembles detailed descriptive information on a large number of cancer cohorts in a searchable database. Impact Information from the CEDCD may assist the interdisciplinary research community by facilitating identification of well-established population resources and large-scale collaborative and integrative research. PMID:27439404

Comparison of cognitive functioning as measured by the Ruff Figural Fluency Test and the CogState computerized battery within the LifeLines Cohort Study.

PubMed

Kuiper, Jisca S; Oude Voshaar, Richard C; Verhoeven, Floor E A; Zuidema, Sytse U; Smidt, Nynke

2017-05-12

The Ruff Figural Fluency Test (RFFT; a pencil and paper test) and the CogState (a computerized cognitive test battery) are well-validated and suitable tests to evaluate cognitive functioning in large observational studies at the population level. The LifeLines Cohort Study includes the RFFT as baseline measurement and incorporated the CogState as replacement for the RFFT at follow-up. It is unknown how these two tests relate to each other. Therefore, the aim of this study is to examine the correlation between the RFFT and the CogState and the impact of demographic characteristics on this association. A subcohort of the LifeLines Cohort Study, a large population based cohort study, participated in this study. Correlations between the RFFT and six subtasks of the CogState were examined. Subgroup analyses were performed to investigate the influence of age, education, and gender on the results. With sensitivity analyses we investigated the influence of computer experience and (physical) impairments. A total of 509 participants (mean age (SD): 53 years (14.6); range 18-87 years) participated in this study. All correlations between the RFFT and the CogState were statistically significant (except for the correlation between the RFFT error ratio and the CogState One Back Task), ranging from -0.39 to 0.28. Stratifying the analyses for age, education, and gender did not substantially affect our conclusions. Sensitivity analyses showed no substantial influence of level of computer experience or (physical) impairments. Correlations found in the present study were only weak to moderate, indicating that cognitive functioning measured by the RFFT does not measure the same components of cognitive functioning as six subtasks of the CogState. Computerized testing such as the CogState may be very well suited for large cohort studies to assess cognitive functioning in the general population and to identify cognitive changes as early as possible, as it is a less time- and labor intensive tool.

Effectiveness of angiotensin II receptor antagonists in a cohort of Dutch patients with type 2 diabetes mellitus (ZODIAC-14).

PubMed

van Hateren, Kornelis J J; Landman, Gijs W D; Groenier, Klaas H; Bilo, Henk J G; Kleefstra, Nanne

2015-04-01

There is limited evidence with respect to the between-group effects of various angiotensin receptor blockers (ARBs) on blood pressure and albuminuria in patients with type 2 diabetes mellitus. Therefore, we aimed to investigate the effects of differing ARBs on systolic blood pressure (SBP) and the albumin-creatinine ratio after 1 year in a large cohort of patients with type 2 diabetes mellitus. In 2007, 24 940 primary care patients with type 2 diabetes mellitus participated in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study, a prospective observational cohort study. Patients were included in the current study if they were prescribed an ARB in 2007 and if 1-year follow-up data were available. The final study population comprised 3610 patients. Multivariate mixed-model analyses were performed to estimate effects of the various ARBs on SBP and albuminuria. Stratified subgroup analyses were performed according to baseline hypertension and albuminuria. SBP decreased in all groups, the largest decrease being observed in the group receiving telmisartan. No significant or relevant changes over time were observed among groups for SBP and albuminuria. In the subgroup (n=1225) of normotensive patients, telmisartan was associated with a larger decrease in SBP after 1 year compared to other ARBs, without different effects on the albumin-creatinine ratio. We observed no differences in effects on SBP and the albumin-creatinine ratio among differing ARBs in patients with type 2 diabetes mellitus. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

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.

Depression in ALS in a large self-reporting cohort.

PubMed

Thakore, Nimish J; Pioro, Erik P

2016-03-15

To report an observational study of depression in a large cohort of patients with amyotrophic lateral sclerosis (ALS), including its prevalence, associations, longitudinal course, and effect on survival. The Patient Health Questionnaire-9 (PHQ-9) (a validated depression instrument) and other self-reported measures were obtained from patients with ALS as part of routine clinical care via tablet devices using a software system (Knowledge Program). Cox proportional hazard models, linear models, mixed effects models, and logistic regression were used for statistical analyses. Of 1,067 patients seen over an 8-year period, 964 had at least one PHQ-9 recorded. Initially, at least moderate (PHQ-9 ≥ 10), moderately severe (PHQ-9 ≥ 15), and severe depression (PHQ-9 ≥ 20) were found in about 33%, 14%, and 5% of patients, respectively. Higher initial PHQ-9 was significantly predictive of mortality (hazard ratio 1.041 per increasing point, 95% confidence interval 1.018-1.065) after controlling for covariates. PHQ-9 was also associated with poorer quality of life. More advanced disease initially and pseudobulbar affect were associated with depression. In 587 patients with repeated PHQ-9 measures, worsening depression was not observed. Depression is prevalent in ALS and is associated with disease severity at initial assessment. Paradoxically, however, worsening depression is not observed during follow-up despite motor progression. Most importantly, depression has detrimental effects on survival and quality of life. Treatment of depression is recommended in ALS, although it is unknown if this would improve survival. © 2016 American Academy of Neurology.

Creating an African HIV Clinical Research and Prevention Trials Network: HIV Prevalence, Incidence and Transmission

PubMed Central

Kamali, Anatoli; Price, Matt A.; Lakhi, Shabir; Karita, Etienne; Inambao, Mubiana; Sanders, Eduard J.; Anzala, Omu; Latka, Mary H.; Bekker, Linda-Gail; Kaleebu, Pontiano; Asiki, Gershim; Ssetaala, Ali; Ruzagira, Eugene; Allen, Susan; Farmer, Paul; Hunter, Eric; Mutua, Gaudensia; Makkan, Heeran; Tichacek, Amanda; Brill, Ilene K.; Fast, Pat; Stevens, Gwynn; Chetty, Paramesh; Amornkul, Pauli N.; Gilmour, Jill

2015-01-01

HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner. PMID:25602351

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.

Seasonal Variations in Mortality, Clinical, and Laboratory Parameters in Hemodialysis Patients: A 5-Year Cohort Study

PubMed Central

Usvyat, Len A.; Carter, Mary; Thijssen, Stephan; Kooman, Jeroen P.; van der Sande, Frank M.; Zabetakis, Paul; Balter, Paul; Levin, Nathan W.; Kotanko, Peter

2012-01-01

Summary Background and objectives Mortality varies seasonally in the general population, but it is unknown whether this phenomenon is also present in hemodialysis patients with known higher background mortality and emphasis on cardiovascular causes of death. This study aimed to assess seasonal variations in mortality, in relation to clinical and laboratory variables in a large cohort of chronic hemodialysis patients over a 5-year period. Design, setting, participants, & measurements This study included 15,056 patients of 51 Renal Research Institute clinics from six states of varying climates in the United States. Seasonal differences were assessed by chi-squared tests and univariate and multivariate cosinor analyses. Results Mortality, both all-cause and cardiovascular, was significantly higher during winter compared with other seasons (14.2 deaths per 100 patient-years in winter, 13.1 in spring, 12.3 in autumn, and 11.9 in summer). The increase in mortality in winter was more pronounced in younger patients, as well as in whites and in men. Seasonal variations were similar across climatologically different regions. Seasonal variations were also observed in neutrophil/lymphocyte ratio and serum calcium, potassium, and platelet values. Differences in mortality disappeared when adjusted for seasonally variable clinical parameters. Conclusions In a large cohort of dialysis patients, significant seasonal variations in overall and cardiovascular mortality were observed, which were consistent over different climatic regions. Other physiologic and laboratory parameters were also seasonally different. Results showed that mortality differences were related to seasonality of physiologic and laboratory parameters. Seasonal variations should be taken into account when designing and interpreting longitudinal studies in dialysis patients. PMID:22096041

Cohort Study of Airway Mycobiome in Adult Cystic Fibrosis Patients: Differences in Community Structure between Fungi and Bacteria Reveal Predominance of Transient Fungal Elements

PubMed Central

Sauer-Heilborn, Annette; Welte, Tobias; Guzman, Carlos A.; Abraham, Wolf-Rainer; Höfle, Manfred G.

2015-01-01

The respiratory mycobiome is an important but understudied component of the human microbiota. Like bacteria, fungi can cause severe lung diseases, but their infection rates are much lower. This study compared the bacterial and fungal communities of sputum samples from a large cohort of 56 adult patients with cystic fibrosis (CF) during nonexacerbation periods and under continuous antibiotic treatment. Molecular fingerprinting based on single-strand conformation polymorphism (SSCP) analysis revealed fundamental differences between bacterial and fungal communities. Both groups of microorganisms were taxonomically classified by identification of gene sequences (16S rRNA and internal transcript spacer), and prevalences of single taxa were determined for the entire cohort. Major bacterial pathogens were frequently observed, whereas fungi of known pathogenicity in CF were detected only in low numbers. Fungal species richness increased without reaching a constant level (saturation), whereas bacterial richness showed saturation after 50 patients were analyzed. In contrast to bacteria, a large number of fungal species were observed together with high fluctuations over time and among patients. These findings demonstrated that the mycobiome was dominated by transient species, which strongly suggested that the main driving force was their presence in inhaled air rather than colonization. Considering the high exposure of human airways to fungal spores, we concluded that fungi have low colonization abilities in CF, and colonization by pathogenic fungal species may be considered a rare event. A comprehensive understanding of the conditions promoting fungal colonization may offer the opportunity to prevent colonization and substantially reduce or even eliminate fungus-related disease progression in CF. PMID:26135861

Recruitment of Hispanics into an observational study of chronic kidney disease: the Hispanic Chronic Renal Insufficiency Cohort Study experience.

PubMed

Lora, Claudia M; Ricardo, Ana C; Brecklin, Carolyn S; Fischer, Michael J; Rosman, Robert T; Carmona, Eunice; Lopez, Amada; Balaram, Manjunath; Nessel, Lisa; Tao, Kaixiang Kelvin; Xie, Dawei; Kusek, John W; Go, Alan S; Lash, James P

2012-11-01

Despite the large burden of chronic kidney disease (CKD) in Hispanics, this population has been underrepresented in research studies. We describe the recruitment strategies employed by the Hispanic Chronic Renal Insufficiency Cohort Study, which led to the successful enrollment of a large population of Hispanic adults with CKD into a prospective observational cohort study. Recruitment efforts by bilingual staff focused on community clinics with Hispanic providers in high-density Hispanic neighborhoods in Chicago, academic medical centers, and private nephrology practices. Methods of publicizing the study included church meetings, local Hispanic print media, Spanish television and radio stations, and local health fairs. From October 2005 to July 2008, we recruited 327 Hispanics aged 21-74 years with mild-to-moderate CKD as determined by age-specific estimated glomerular filtration rate (eGFR). Of 716 individuals completing a screening visit, 49% did not meet eGFR inclusion criteria and 46% completed a baseline visit. The mean age at enrollment was 57.1 and 67.1% of participants were male. Approximately 75% of enrolled individuals were Mexican American, 15% Puerto Rican, and 10% had other Latin American ancestry. Eighty two percent of participants were Spanish-speakers. Community-based and academic primary care clinics yielded the highest percentage of participants screened (45.9% and 22.4%) and enrolled (38.2% and 24.5%). However, academic and community-based specialty clinics achieved the highest enrollment yield from individuals screened (61.9% to 71.4%). A strategy focused on primary care and nephrology clinics and the use of bilingual recruiters allowed us to overcome barriers to the recruitment of Hispanics with CKD. Copyright © 2012 Elsevier Inc. All rights reserved.

Chocolate Intake and Incidence of Heart Failure: Findings from the Cohort of Swedish Men

PubMed Central

Steinhaus, Daniel A.; Mostofsky, Elizabeth; Levitan, Emily B.; Dorans, Kirsten S.; Håkansson, Niclas; Wolk, Alicja; Mittleman, Murray A.

2016-01-01

Aims The objective of this study was to evaluate the association of chocolate consumption and heart failure in a large population of Swedish men. Methods and Results We conducted a prospective cohort study of 31,917 men 45-79 years old with no history of myocardial infarction, diabetes, or HF at baseline who were participants in the population-based Cohort of Swedish Men (COSM) study. Chocolate consumption was assessed through a self-administrated food frequency questionnaire. Participants were followed for HF hospitalization or mortality from January 1, 1998 to December 31, 2011 using record linkage to the Swedish inpatient and cause-of-death registries. During 14 years of follow up, 2,157 men were hospitalized (n = 1901) or died from incident HF (n = 256). Compared with subjects who reported no chocolate intake, the multivariable-adjusted rate ratio of HF was 0.88 (95%CI 0.78-0.99) for those consuming 1-3 servings per month, 0.83 (95%CI 0.72-0.94) for those consuming 1-2 servings per week, 0.82 (95%CI 0.68-0.99) for those consuming 3-6 servings per week, and 1.10 (95%CI 0.84-1.45) for those consuming ≥1 servings per day (P for quadratic trend= 0.001). Conclusions In this large prospective cohort study, there was a J-shaped relationship between chocolate consumption and HF incidence. Moderate chocolate consumption was associated with a lower rate of HF hospitalization or death, but the protective association was not observed among individuals consuming ≥1 servings per day. PMID:27979037

Birth order and risk of childhood cancer in the Danish birth cohort of 1973-2010.

PubMed

Schüz, Joachim; Luta, George; Erdmann, Friederike; Ferro, Gilles; Bautz, Andrea; Simony, Sofie Bay; Dalton, Susanne Oksbjerg; Lightfoot, Tracy; Winther, Jeanette Falck

2015-11-01

Many studies have investigated the possible association between birth order and risk of childhood cancer, although the evidence to date has been inconsistent. Birth order has been used as a marker for various in utero or childhood exposures and is relatively straightforward to assess. Data were obtained on all children born in Denmark between 1973 and 2010, involving almost 2.5 million births and about 5,700 newly diagnosed childhood cancers before the age of 20 years. Data were analyzed using Poisson regression models. We failed to observe associations between birth order and risk of any childhood cancer subtype, including acute lymphoblastic leukemia; all rate ratios were close to one. Further analyses stratified by birth cohort (those born between 1973 and 1990, and those born between 1991 and 2010) also failed to show any associations. Considering stillbirths and/or controlling for birth weight and parental age in the analyses had no effect on the results. Analyses by years of birth (those born between 1973 and 1990, and those born between 1991 and 2010) did not show any changes in the overall pattern of no association. In this large cohort of all children born in Denmark over an almost 40-year period, we did not observe an association between birth order and the risk of childhood cancer.

Coffee consumption and risk of colorectal cancer in a population-based prospective cohort of Japanese men and women.

PubMed

Lee, Kyung-Jae; Inoue, Manami; Otani, Tetsuya; Iwasaki, Motoki; Sasazuki, Shizuka; Tsugane, Shoichiro

2007-09-15

We prospectively examined the association between coffee consumption and the risk of developing colorectal cancer in a large population-based cohort study (the JPHC Study) of Japanese men and women. Data were analyzed from a population-based cohort of 96,162 subjects (46,023 men and 50,139 women). A total of 1,163 incident colorectal cancers were identified during the follow-up period, including 763 cases of colon cancer and 400 of rectal cancer. We observed a significant inverse association between coffee consumption and the risk of developing invasive colon cancer among women. Compared with those who almost never consumed coffee, women who regularly consumed 3 or more cups of coffee per day had a RR of 0.44 (95% CI = 0.19-1.04; p for trend = 0.04) after adjustment for potential confounding factors. However, no significant association was found for rectal cancer in women. In men, no significant decrease was observed in any colorectal cancer site. Further, additional analyses on the association of green tea consumption with colorectal cancer risk found no significant association in men or women. These findings suggest that coffee consumption may lower the risk of colon cancer among Japanese women. (c) 2007 Wiley-Liss, Inc.

Characteristics of the musculoskeletal symptoms observed among survivors of Ebola virus disease in the Postebogui cohort in Guinea.

PubMed

Pers, Yves-Marie; Sow, Mamadou Saliou; Taverne, Bernard; March, Laura; Izard, Suzanne; Étard, Jean François; Barry, Moumié; Touré, Abdoulaye; Delaporte, Eric

2017-12-01

Previous studies show that arthralgia is the most common symptom experienced by Ebola virus disease (EVD) survivors. Nevertheless, specific analyses of rheumatological sequelea are still lacking. The Postebogui study is a prospective, multicentre cohort aiming to evaluate the long-term outcomes of EVD survivors infected during the 2014-15 outbreak in Guinea. Of the 216 participants enrolled in the study in October 2015, 44 patients with arthralgia/myalgia underwent a physical examination by a rheumatologist (the Eborheum cohort). Data were collected using a standardized questionnaire. In the Eborheum cohort, 61% of patients were female, the median age was 31.1 years, and the median time from Ebola Treatment Centre discharge was 8.8 months. Pain manifestation started after Ebola infection in all but one patient. Patients had mainly both mechanical and inflammatory pain (45%) and low back pain (77%). All patients reported pain in at least one peripheral joint. Pain in large joints was more frequently reported than in small joints (73 vs 41%). Oligo- and polyarticular presentations were similar, with symmetrical pain distribution. Furthermore, 36 patients had at least one painful 18-tender point count, most of whom reported extensive pain (n = 19) and symmetrical distribution (91%). Diagnoses were mainly non-specific musculoskeletal disorders (59%) and mechanical back pain (52%). No polyarthritis was observed. We found a higher percentage of depressed patients compared with the remaining Postebogui group (42 vs 11%; P < 0.001). Results from the study come from the first complete rheumatological examination of a cohort of EVD survivors, nearly 9 months after Ebola Treatment Centre discharge. Importantly, we found that patients with arthralgia/myalgia included in the Eborheum cohort were more likely to experience depression than survivors not reporting these symptoms, highlighting the impact of pain symptoms among survivors. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

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.

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

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.

Does educational status impact adult mortality in Denmark? A twin approach.

PubMed

Madsen, Mia; Andersen, Anne-Marie Nybo; Christensen, Kaare; Andersen, Per Kragh; Osler, Merete

2010-07-15

To disentangle an independent effect of educational status on mortality risk from direct and indirect selection mechanisms, the authors used a discordant twin pair design, which allowed them to isolate the effect of education by means of adjustment for genetic and environmental confounding per design. The study is based on data from the Danish Twin Registry and Statistics Denmark. Using Cox regression, they estimated hazard ratios for mortality according to the highest attained education among 5,260 monozygotic and 11,088 dizygotic same-sex twin pairs born during 1921-1950 and followed during 1980-2008. Both standard cohort and intrapair analyses were conducted separately for zygosity, gender, and birth cohort. Educational differences in mortality were demonstrated in the standard cohort analyses but attenuated in the intrapair analyses in all subgroups but men born during 1921-1935, and no effect modification by zygosity was observed. Hence, the results are most compatible with an effect of early family environment in explaining the educational inequality in mortality. However, large educational differences were still reflected in mortality risk differences within twin pairs, thus supporting some degree of independent effect of education. In addition, the effect of education may be more pronounced in older cohorts of Danish men.

Seasonal Variation of Dystocia in a Large Danish Cohort

PubMed Central

Rohr Thomsen, Christine; Uldbjerg, Niels; Hvidman, Lone; Atladóttir, Hjördís Ósk; Henriksen, Tine Brink; Milidou, Ioanna

2014-01-01

Background Dystocia is one of the most frequent causes of cesarean delivery in nulliparous women. Despite this, its causes are largely unknown. Vitamin D receptor (VDR) has been found in the myometrium. Thus, it is possible that vitamin D affects the contractility of the myometrium and may be involved in the pathogenesis of dystocia. Seasonal variation of dystocia in areas with distinct seasonal variation in sunlight exposure, like Denmark, could imply that vitamin D may play a role. This study examined whether there was seasonal variation in the incidence of dystocia in a Danish population. Method We used information from a cohort of 34,261 nulliparous women with singleton pregnancies, spontaneous onset of labor between 37 and 42 completed gestational weeks, and vertex fetal presentation. All women gave birth between 1992 and 2010 at the Department of Obstetrics and Gynecology, Aarhus University Hospital, Skejby. Logistic regression combined with cubic spline was used to estimate the seasonal variation for each outcome after adjusting for calendar time. Results No evidence for seasonal variation was found for any of the outcomes: acute cesarean delivery due to dystocia (p = 0.44); instrumental vaginal delivery due to dystocia (p = 0.69); oxytocin augmentation due to dystocia (p = 0.46); and overall dystocia (p = 0.91). Conclusion No seasonal variation in the incidence of dystocia was observed in a large cohort of Danish women. This may reflect no association between vitamin D and dystocia, or alternatively that other factors with seasonal variation and influence on the occurrence of dystocia attenuate such an association. PMID:24736600

Seasonal variation of dystocia in a large Danish cohort.

PubMed

Rohr Thomsen, Christine; Uldbjerg, Niels; Hvidman, Lone; Atladóttir, Hjördís Ósk; Henriksen, Tine Brink; Milidou, Ioanna

2014-01-01

Dystocia is one of the most frequent causes of cesarean delivery in nulliparous women. Despite this, its causes are largely unknown. Vitamin D receptor (VDR) has been found in the myometrium. Thus, it is possible that vitamin D affects the contractility of the myometrium and may be involved in the pathogenesis of dystocia. Seasonal variation of dystocia in areas with distinct seasonal variation in sunlight exposure, like Denmark, could imply that vitamin D may play a role. This study examined whether there was seasonal variation in the incidence of dystocia in a Danish population. We used information from a cohort of 34,261 nulliparous women with singleton pregnancies, spontaneous onset of labor between 37 and 42 completed gestational weeks, and vertex fetal presentation. All women gave birth between 1992 and 2010 at the Department of Obstetrics and Gynecology, Aarhus University Hospital, Skejby. Logistic regression combined with cubic spline was used to estimate the seasonal variation for each outcome after adjusting for calendar time. No evidence for seasonal variation was found for any of the outcomes: acute cesarean delivery due to dystocia (p = 0.44); instrumental vaginal delivery due to dystocia (p = 0.69); oxytocin augmentation due to dystocia (p = 0.46); and overall dystocia (p = 0.91). No seasonal variation in the incidence of dystocia was observed in a large cohort of Danish women. This may reflect no association between vitamin D and dystocia, or alternatively that other factors with seasonal variation and influence on the occurrence of dystocia attenuate such an association.

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

Confirming the cognition of rising scores: Fox and Mitchum (2013) predicts violations of measurement invariance in series completion between age-matched cohorts.

PubMed

Fox, Mark C; Mitchum, Ainsley L

2014-01-01

The trend of rising scores on intelligence tests raises important questions about the comparability of variation within and between time periods. Descriptions of the processes that mediate selection of item responses provide meaningful psychological criteria upon which to base such comparisons. In a recent paper, Fox and Mitchum presented and tested a cognitive theory of rising scores on analogical and inductive reasoning tests that is specific enough to make novel predictions about cohort differences in patterns of item responses for tests such as the Raven's Matrices. In this paper we extend the same proposal in two important ways by (1) testing it against a dataset that enables the effects of cohort to be isolated from those of age, and (2) applying it to two other inductive reasoning tests that exhibit large Flynn effects: Letter Series and Word Series. Following specification and testing of a confirmatory item response model, predicted violations of measurement invariance are observed between two age-matched cohorts that are separated by only 20 years, as members of the later cohort are found to map objects at higher levels of abstraction than members of the earlier cohort who possess the same overall level of ability. Results have implications for the Flynn effect and cognitive aging while underscoring the value of establishing psychological criteria for equating members of distinct groups who achieve the same scores.

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

Retrospective study of intravascular large B-cell lymphoma cases diagnosed in Quebec: A retrospective study of 29 case reports.

PubMed

Brunet, Vanessa; Marouan, Sofia; Routy, Jean-Pierre; Hashem, Mohamed Amin; Bernier, Vincent; Simard, Raynald; Petrella, Tony; Lamarre, Louis; Théorêt, Gilles; Carrier, Christian; Knecht, Hans; Fleury, Isabelle; Pavic, Michel

2017-02-01

Intravascular large B-cell lymphoma (IVL) is an extremely rare malignancy, mainly studied through European and Asian series. Due to the low incidence of this condition, our understanding of the clinical presentation as well as the management of IVL relies on a limited number of patients.We report the largest North American study to date on IVL with 29 cases from Quebec hospital diagnosed between 1990 and 2016. The aim of our study is to describe the clinical presentations, diagnostic and staging procedures, therapeutic management and clinical outcomes of IVL patients in our population and compare the disease phenotype to European and Asian series reported.In our cohort, all patients had stage IV IVL at diagnosis, with a median age of 66.7 years (range 47.2-90.8). Clinical presentation was characterized by constitutional symptoms (100%), poor ECOG-PS (100% ≥ 2), cytopenias (93% anemia), and elevated lactate dehydrogenase (97%) and C-reactive protein (96%). Our cohort presented with mainly cutaneous and neurological symptoms. However, neurological involvement (75.9%) was predominant and no "cutaneous variant" was observed; this differs from European literature, where "classical" IVL is reported with mainly cutaneous involvement. Two of our Caucasian patients presented "Asian variant" IVL; this observation is not unusual, as cases of "classical" IVL have been reported in Asians and "Asian variant" IVL has been reported in Europeans. All patients were classified according to their immunophenotypic features in 3 different subgroups (CD5 or CD5CD10, CD5CD10, CD5CD10) with no difference in outcome. Finally, 62% of our cohort received anthracycline-based chemotherapy and 53% of them achieved a complete response. After a median follow-up of 328 days, OS at 3 years was 42.7% for the entire cohort and 47.4% for the cases with in vivo diagnosis. Unlike European studies on "classical" IVL, our study showed that the French Canadian presentation of this subtype of IVL is more frequently observed with neurological rather than cutaneous involvement. Finally, an early diagnosis is of primary importance since almost a quarter of patients receive a post-mortem diagnosis. A prompt diagnosis allows the introduction of an early treatment, associated with a CR in 53% of patients.

Pregnancy and birth cohort resources in europe: a large opportunity for aetiological child health research.

PubMed

Larsen, Pernille Stemann; Kamper-Jørgensen, Mads; Adamson, Ashley; Barros, Henrique; Bonde, Jens Peter; Brescianini, Sonia; Brophy, Sinead; Casas, Maribel; Charles, Marie-Aline; Devereux, Graham; Eggesbø, Merete; Fantini, Maria Pia; Frey, Urs; Gehring, Ulrike; Grazuleviciene, Regina; Henriksen, Tine Brink; Hertz-Picciotto, Irva; Heude, Barbara; Hryhorczuk, Daniel O; Inskip, Hazel; Jaddoe, Vincent W V; Lawlor, Debbie A; Ludvigsson, Johnny; Kelleher, Cecily; Kiess, Wieland; Koletzko, Berthold; Kuehni, Claudia Elisabeth; Kull, Inger; Kyhl, Henriette Boye; Magnus, Per; Momas, Isabelle; Murray, Dierdre; Pekkanen, Juha; Polanska, Kinga; Porta, Daniela; Poulsen, Gry; Richiardi, Lorenzo; Roeleveld, Nel; Skovgaard, Anne Mette; Sram, Radim J; Strandberg-Larsen, Katrine; Thijs, Carel; Van Eijsden, Manon; Wright, John; Vrijheid, Martine; Andersen, Anne-Marie Nybo

2013-07-01

During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500,000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics. © 2013 John Wiley & Sons Ltd.

Therapeutic priorities for solitary large hepatocellular carcinoma in a hepatitis B virus endemic area; an analysis of a nationwide cancer registry database.

PubMed

Jin, Young-Joo; Lee, Jin-Woo

2017-03-01

We compared overall survival (OS) of patients with a solitary large (>5 cm) hepatocellular carcinoma (HCC) treated surgically or by transarterial chemoembolization (TACE). The archived records of HCC patients registered at the Korean Central Cancer Registry from 2003 through 2005 (registry A, n = 4 520) or from 2008 through 2010 (registry B, n = 4 596) were retrospectively analyzed. In these registries, 578 and 315 patients had a single large HCC, respectively. In registry A, 442 (cohort A) underwent surgery (n = 96) or TACE (n = 346). In registry B, 253 (cohort B) underwent surgery (n = 110) or TACE (n = 143). Cohort C (n = 695) was constructed by combining cohorts A and B, and thus, 206 and 489 patients received surgery and TACE, respectively. In cohort C, cumulative OS rates at 1-, 3-, and 5-years were significantly higher for surgery than TACE (89.3%, 67.4%, and 58.0% vs 67.7%, 38.2%, and 27.2%, respectively, P < 0.001). Similar results were obtained for cohorts A and B, even after propensity-score matching in three cohorts (P values for all <0.05). TACE (HR 2.18, P < 0.001), serum albumin (HR 0.77, P = 0.015), and tumor size (HR 1.06, P < 0.001) were predictors of post-treatment mortality. Surgery is associated with improved OS for a solitary large HCC of BCLC stage A. © 2016 Wiley Periodicals, Inc.

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.

The Cancer Epidemiology Descriptive Cohort Database: A Tool to Support Population-Based Interdisciplinary Research.

PubMed

Kennedy, Amy E; Khoury, Muin J; Ioannidis, John P A; Brotzman, Michelle; Miller, Amy; Lane, Crystal; Lai, Gabriel Y; Rogers, Scott D; Harvey, Chinonye; Elena, Joanne W; Seminara, Daniela

2016-10-01

We report on the establishment of a web-based Cancer Epidemiology Descriptive Cohort Database (CEDCD). The CEDCD's goals are to enhance awareness of resources, facilitate interdisciplinary research collaborations, and support existing cohorts for the study of cancer-related outcomes. Comprehensive descriptive data were collected from large cohorts established to study cancer as primary outcome using a newly developed questionnaire. These included an inventory of baseline and follow-up data, biospecimens, genomics, policies, and protocols. Additional descriptive data extracted from publicly available sources were also collected. This information was entered in a searchable and publicly accessible database. We summarized the descriptive data across cohorts and reported the characteristics of this resource. As of December 2015, the CEDCD includes data from 46 cohorts representing more than 6.5 million individuals (29% ethnic/racial minorities). Overall, 78% of the cohorts have collected blood at least once, 57% at multiple time points, and 46% collected tissue samples. Genotyping has been performed by 67% of the cohorts, while 46% have performed whole-genome or exome sequencing in subsets of enrolled individuals. Information on medical conditions other than cancer has been collected in more than 50% of the cohorts. More than 600,000 incident cancer cases and more than 40,000 prevalent cases are reported, with 24 cancer sites represented. The CEDCD assembles detailed descriptive information on a large number of cancer cohorts in a searchable database. Information from the CEDCD may assist the interdisciplinary research community by facilitating identification of well-established population resources and large-scale collaborative and integrative research. Cancer Epidemiol Biomarkers Prev; 25(10); 1392-401. ©2016 AACR. ©2016 American Association for Cancer Research.

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

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

PubMed

Sacchetti, Emilio; Turrina, Cesare; Valsecchi, Paolo

2010-04-01

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

Chronic Neurodegenerative Illnesses and Epilepsy in Danish Adventists and Baptists: A Nationwide Cohort Study.

PubMed

Thygesen, Lau Caspar; Gimsing, Louise NØrreslet; Bautz, Andrea; Hvidt, Niels Christian; Johansen, Christoffer

2017-01-01

Limited knowledge of the influence of lifestyle risk factors and religious living on chronic neurological diseases exists. Seventh-day Adventists (SDA) do not consume tobacco, alcohol, or pork, and many adhere to lacto-ovo-vegetarian diet, and Baptists discourage excessive use of alcohol and tobacco. We investigated whether the incidence of four common chronic neurological illnesses: dementia, Alzheimer's disease, Parkinson's disease, and epilepsy in a large cohort of Danish Adventists and Baptists was different compared to the general Danish population. Three of the illnesses are neurodegenerative, whereas epilepsy can occur at any age. We compared hospital admission rates for some major neurological diseases among members of the Danish Religious Societies Health Study comprising 6,532 SDA and 3,720 Baptists with the general Danish population. Standardized incidence ratios (SIR) stratified by sex, age, and calendar time were calculated. SIR of dementia or Alzheimer's disease was significantly decreased for members of both communities (SDA, 0.78; 95% CI, 0.67-#x2013;0.90 and Baptists, 0.59; 0.47-#x2013;0.73). The SIRs of Parkinson's disease and epilepsy were not significantly different compared to the general population. We observe reduced incidence for dementia or Alzheimer's disease in a large cohort of members of two religious communities characterized by lifestyle recommendations. More studies are needed to disentangle the interaction between such lifestyle and other components of the religious belief system.

[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.

Higher serum levels of vitamin D at diagnosis are associated with better survival in a prospective cohort of 1,666 women with breast cancer: A case-cohort analysis in the Pathways Study

PubMed Central

Yao, Song; Kwan, Marilyn L.; Ergas, Isaac J.; Roh, Janise M.; Cheng, Ting-Yuan David; Hong, Chi-Chen; McCann, Susan E.; Tang, Li; Davis, Warren; Liu, Song; Quesenberry, Charles P.; Lee, Marion M.; Ambrosone, Christine B.; Kushi, Lawrence H.

2017-01-01

Importance There are long-standing interests in the potential benefits of vitamin D for preventing breast cancer recurrence and mortality; yet data from prospective cohort studies are limited. Objective We investigated a serum biomarker of vitamin D status, 25-hydroxyvitamin D (25OHD) measured at the time of breast cancer diagnosis, with prognosis. Design The Pathways Study is a prospective cohort study of breast cancer survivors established in 2006. Enrollment was completed in 2013; follow up is ongoing. Setting The cohort was established in Kaiser Permanente Northern California (KPNC), a large integrated healthcare delivery system in San Francisco Bay Area and central valley, California. Participants Women diagnosed with incident invasive breast cancer were typically consented and enrolled within 2 months of diagnosis. The overall enrollment rate was 46%. Participants are followed for health outcomes and comorbidities at 12, 24, 48, 72 and 96 months after baseline interview. A case-cohort design was used for efficiency assay of 25OHD, selecting 1,666 cohort members with serum samples and ensuring representation in the sub-cohort of races and clinical subtypes. Main Outcome Measures Primary outcomes are breast cancer recurrence, second primary cancer (SPC), and death. Results Serum 25OHD concentrations were lower in women with advanced stage tumors, and the lowest in premenopausal women with triple-negative cancer. Levels were also inversely associated with hazards of disease progression and death. Compared with the lowest tertile (T1), women with the highest (T3) 25OHD levels had superior overall survival (OS). This association remained after adjustment for clinical prognostic factors [hazards ratio (HR)=0.72, 95% confidence interval (CI): 0.54, 0.98]. Among premenopausal women, the association with OS was stronger, and there were also associations with breast cancer-specific survival (BCSS) and invasive disease-free survival (IDFS) (OS: HR=0.45, 95% CI, 0.21–0.96; BCSS: HR=0.37, 95% CI, 0.15–0.93; IDFS: HR=0.58, 95% CI, 0.34–1.01; all after full adjustment.) Conclusions and Relevance Serum 25OHD levels were independently associated with breast cancer prognostic characteristics and patient prognosis, most prominently among premenopausal women. Our findings from a large, well-characterized prospective cohort provide compelling observational evidence on associations of vitamin D with lower risk of breast cancer morbidity and mortality. PMID:27832250

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.

Insulin detemir improves glycemic control and reduces hypoglycemia in children with type 1 diabetes: findings from the Turkish cohort of the PREDICTIVE observational study.

PubMed

Kurtoglu, Selim; Atabek, Mehmet Emre; Dizdarer, Ceyhun; Pirgon, Ozgur; Isguven, Pinar; Emek, Sevil

2009-09-01

Insulin detemir is a basal insulin analog designed to produce a superior pharmacokinetic profile to basal formulations of human insulin. It has shown consistently improved tolerability in comparison to neutral protamine Hagedorn (NPH) insulin in adult cohorts, but there are relatively few publications involving pediatric cohorts. The efficacy and safety of insulin detemir in children with type 1 diabetes was assessed using data from the Turkish cohort of PREDICTIVE (a large, multinational, observational) study. The children investigated were using basal-bolus therapy involving NPH insulin or insulin glargine at baseline but were switched to insulin detemir as part of routine clinical care by their physicians. Twelve weeks of treatment with insulin detemir significantly reduced mean hemoglobin A1c (9.7-8.9%, p < 0.001) and mean fasting glucose [185-162 mg/dL (10.3-9 mmol/L), p < 0.01]. Fasting glucose variability was also lower after treatment with insulin detemir than previously (on either NPH or glargine, p < 0.05). The frequencies of total, major and nocturnal hypoglycemic events were significantly reduced with insulin detemir relative to baseline, with an estimated mean of 6.89 fewer events/patient/yr overall (p < 0.001) and 2.6 fewer nocturnal events/patient/yr (p < 0.01). Weight and insulin dose remained relatively unchanged. Twelve weeks of treatment with insulin detemir improved glycemic control and reduced hypoglycemia in children with type 1 diabetes. This improved tolerability might allow further dose titration and therefore additional improvements in glucose control.

Enrichment of clinically relevant organisms in spontaneous preterm delivered placenta and reagent contamination across all clinical groups in a large UK pregnancy cohort.

PubMed

Leon, Lydia J; Doyle, Ronan; Diez-Benavente, Ernest; Clark, Taane G; Klein, Nigel; Stanier, Philip; Moore, Gudrun E

2018-05-18

In this study differences in the placental microbiota of term and preterm deliveries from a large UK pregnancy cohort were studied using 16S targeted amplicon sequencing. The impact of contamination from DNA extraction, PCR reagents, as well as those from delivery itself were also examined. A total of 400 placental samples from 256 singleton pregnancies were analysed and differences investigated between spontaneous preterm, non-spontaneous preterm, and term delivered placenta. DNA from recently delivered placenta was extracted, and screening for bacterial DNA was carried out using targeted sequencing of the 16S rRNA gene on the Illumina MiSeq platform. Sequenced reads were analysed for presence of contaminating operational taxonomic units (OTUs) identified via sequencing of negative extraction and PCR blank samples. Differential abundance and between sample (beta) diversity metrics were then compared. A large proportion of the reads sequenced from the extracted placental samples mapped to OTUs that were also found in negative extractions. Striking differences in the composition of samples were also observed, according to whether the placenta was delivered abdominally or vaginally, providing strong circumstantial evidence for delivery contamination as an important contributor to observed microbial profiles. When OTU and genus level abundances were compared between the groups of interest, a number of organisms were enriched in the spontaneous preterm cohort, including organisms that have been previously associated with adverse pregnancy outcomes, specifically Mycoplasma spp., and Ureaplasma spp.. However, analyses of overall community structure did not reveal convincing evidence for the existence of a reproducible 'preterm placental microbiome'. IMPORTANCE Preterm birth is associated with both psychological and physical disabilities and is the leading cause of infant morbidity and mortality worldwide. Infection is known to be an important cause of spontaneous preterm birth, and recent research has implicated variation in the 'placental microbiome' with preterm birth risk. Consistent with previous studies, the abundance of certain clinically relevant species differed between spontaneous preterm and non-spontaneous preterm or term delivered placenta. These results support the view that a proportion of spontaneous preterm births have an intra-uterine infection component. However, an additional observation from this study was that a substantial proportion of reads sequenced were contaminating reads, rather than DNA from endogenous, clinically relevant species. This observation warrants caution in the interpretation of sequencing output from such low biomass samples as the placenta. Copyright © 2018 Leon et al.

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

A new mechanistic approach for the further development of a population with established size bimodality

USGS Publications Warehouse

Heerman, Lisa; DeAngelis, Donald L.; Borcherding, Jost

2017-01-01

Usually, the origin of a within-cohort bimodal size distribution is assumed to be caused by initial size differences or by one discrete period of accelerated growth for one part of the population. The aim of this study was to determine if more continuous pathways exist allowing shifts from the small to the large fraction within a bimodal age-cohort. Therefore, a Eurasian perch population, which had already developed a bimodal size-distribution and had differential resource use of the two size-cohorts, was examined. Results revealed that formation of a bimodal size-distribution can be a continuous process. Perch from the small size-cohort were able to grow into the large size-cohort by feeding on macroinvertebrates not used by their conspecifics. The diet shifts were accompanied by morphological shape changes. Intra-specific competition seemed to trigger the development towards an increasing number of large individuals. A stage-structured matrix model confirmed these assumptions. The fact that bimodality can be a continuous process is important to consider for the understanding of ecological processes and links within ecosystems.

A new mechanistic approach for the further development of a population with established size bimodality

PubMed Central

DeAngelis, Donald L.; Borcherding, Jost

2017-01-01

Usually, the origin of a within-cohort bimodal size distribution is assumed to be caused by initial size differences or by one discrete period of accelerated growth for one part of the population. The aim of this study was to determine if more continuous pathways exist allowing shifts from the small to the large fraction within a bimodal age-cohort. Therefore, a Eurasian perch population, which had already developed a bimodal size-distribution and had differential resource use of the two size-cohorts, was examined. Results revealed that formation of a bimodal size-distribution can be a continuous process. Perch from the small size-cohort were able to grow into the large size-cohort by feeding on macroinvertebrates not used by their conspecifics. The diet shifts were accompanied by morphological shape changes. Intra-specific competition seemed to trigger the development towards an increasing number of large individuals. A stage-structured matrix model confirmed these assumptions. The fact that bimodality can be a continuous process is important to consider for the understanding of ecological processes and links within ecosystems. PMID:28650963

A retrospective cohort mortality study of blending and packaging workers of Mobil Corporation.

PubMed

Collingwood, K W; Milcarek, B I; Raabe, G K

1991-01-01

This retrospective cohort mortality study examined 2,467 workers in lubrication products blending and packaging (B&P) operations at two refineries of Mobil Corporation between January 1, 1945 and December 31, 1978. Ninety-seven percent were male. Compared with U.S. males, there were significantly fewer deaths observed among males due to all causes, external causes, and diseases of the circulatory, respiratory, digestive, and genitourinary systems. Deaths observed from all cancer were fewer than expected, although not statistically significant. No statistically significant excess cause-specific mortality occurred at B&P facilities combined or separately. Nonsignificant increases in mortality were observed for cancers of the stomach, large intestine, prostate, the category of "other lymphatic tissue" cancer, and leukemia and aleukemia. Analyses demonstrated a statistically significant pattern of increasing SMR with employment duration for "other lymphatic tissue" cancer. Within the highest cumulative duration of employment category, the excess was confined to workers after 30 or more years since first employment. Although the interpretation of cancer mortality patterns is limited due to small numbers of deaths, the absence of associations with specific B&P departments is evidence against a causal interpretation.

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

PubMed

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

2018-04-01

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

The apparent breastfeeding paradox in very preterm infants: relationship between breast feeding, early weight gain and neurodevelopment based on results from two cohorts, EPIPAGE and LIFT

PubMed Central

Darmaun, Dominique; Boquien, Clair-Yves; Flamant, Cyril; Picaud, Jean-Charles; Savagner, Christophe; Claris, Olivier; Lapillonne, Alexandre; Mitanchez, Delphine; Branger, Bernard; Simeoni, Umberto; Kaminski, Monique; Ancel, Pierre-Yves

2012-01-01

Context Supplementation of breast milk is difficult once infants suckle the breast and is often discontinued at end of hospitalisation and after discharge. Thus, breastfed preterm infants are exposed to an increased risk of nutritional deficit with a possible consequence on neurodevelopmental outcome. Objective To assess the relationship between breast feeding at time of discharge, weight gain during hospitalisation and neurodevelopmental outcome. Design Observational cohort study. Setting Two large, independent population-based cohorts of very preterm infants: the Loire Infant Follow-up Team (LIFT) and the EPIPAGE cohorts. Patients 2925 very preterm infants alive at discharge. Main outcome measure Suboptimal neurodevelopmental outcome, defined as a score in the lower tercile, using Age and Stages Questionnaire at 2 years in LIFT and Kaufman Assessment Battery for Children Test at 5 years in EPIPAGE. Two propensity scores for breast feeding at discharge, one for each cohort, were used to reduce bias. Results Breast feeding at time of discharge concerned only 278/1733 (16%) infants in LIFT and 409/2163 (19%) infants in EPIPAGE cohort. Breast feeding is significantly associated with an increased risk of losing one weight Z-score during hospitalisation (LIFT: n=1463, adjusted odd ratio (aOR)=2.51 (95% CI 1.87 to 3.36); EPIPAGE: n=1417, aOR=1.55 (95% CI 1.14 to 2.12)) and with a decreased risk for a suboptimal neurodevelopmental assessment (LIFT: n=1463, aOR=0.63 (95% CI 0.45 to 0.87); EPIPAGE: n=1441, aOR=0.65 (95% CI 0.47 to 0.89) and an increased chance of having a head circumference Z-score higher than 0.5 at 2 years in LIFT cohort (n=1276, aOR=1.43 (95% CI 1.02 to 2.02)) and at 5 years in EPIPAGE cohort (n=1412, aOR=1.47 (95% CI 1.10 to 1.95)). Conclusions The observed better neurodevelopment in spite of suboptimal initial weight gain could be termed the ‘apparent breastfeeding paradox’ in very preterm infants. Regardless of the mechanisms involved, the current data provide encouragement for the use of breast feeding in preterm infants. PMID:22492388

XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing.

PubMed

Piton, Amélie; Redin, Claire; Mandel, Jean-Louis

2013-08-08

Because of the unbalanced sex ratio (1.3-1.4 to 1) observed in intellectual disability (ID) and the identification of large ID-affected families showing X-linked segregation, much attention has been focused on the genetics of X-linked ID (XLID). Mutations causing monogenic XLID have now been reported in over 100 genes, most of which are commonly included in XLID diagnostic gene panels. Nonetheless, the boundary between true mutations and rare non-disease-causing variants often remains elusive. The sequencing of a large number of control X chromosomes, required for avoiding false-positive results, was not systematically possible in the past. Such information is now available thanks to large-scale sequencing projects such as the National Heart, Lung, and Blood (NHLBI) Exome Sequencing Project, which provides variation information on 10,563 X chromosomes from the general population. We used this NHLBI cohort to systematically reassess the implication of 106 genes proposed to be involved in monogenic forms of XLID. We particularly question the implication in XLID of ten of them (AGTR2, MAGT1, ZNF674, SRPX2, ATP6AP2, ARHGEF6, NXF5, ZCCHC12, ZNF41, and ZNF81), in which truncating variants or previously published mutations are observed at a relatively high frequency within this cohort. We also highlight 15 other genes (CCDC22, CLIC2, CNKSR2, FRMPD4, HCFC1, IGBP1, KIAA2022, KLF8, MAOA, NAA10, NLGN3, RPL10, SHROOM4, ZDHHC15, and ZNF261) for which replication studies are warranted. We propose that similar reassessment of reported mutations (and genes) with the use of data from large-scale human exome sequencing would be relevant for a wide range of other genetic diseases. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

SHIFT WORK AND BREAST CANCER AMONG WOMEN TEXTILE WORKERS IN SHANGHAI, CHINA

PubMed Central

Li, Wenjin; Ray, Roberta M.; Thomas, David B.; Davis, Scott; Yost, Michael; Breslow, Norman; Gao, Dao Li; Fitzgibbons, E. Dawn; Camp, Janice E.; Wong, Eva; Wernli, Karen J.; Checkoway, Harvey

2014-01-01

PURPOSE Although night shift work has been associated with elevated risk of breast cancer in numerous epidemiologic studies, evidence is not consistent. We conducted a nested case-cohort study to investigate a possible association between shift work including a night shift and risk of breast cancer within a large cohort of women textile workers in Shanghai, China. METHODS The study included 1709 incident breast cancer cases and 4780 non-cases. Data on historical shift-work schedules were collected by categorized jobs from the factories where the study subjects had worked, and then were linked to the complete work histories of each subject. No jobs in the factories involved exclusively night shift work. Therefore, night shift was evaluated as part of a rotating shift work pattern. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards modeling adapted for the case-cohort design for years of night-shift work and the total number of nights worked. Additionally, analyses were repeated with exposures lagged by 10 and 20 years. RESULTS We observed no associations with either years of night-shift work, or number of nights worked during the entire employment period, irrespective of lag intervals. Findings from the age-stratified analyses were very similar to those observed for the entire study population. CONCLUSIONS The findings from this study provide no evidence to support the hypothesis that shift work increases breast cancer risk. The positive association between shift work and breast cancer observed in Western populations, but not observed in this and other studies of the Chinese population, suggest that the effect of shift work on breast cancer risk may be different in Asian and Caucasian women. PMID:25421377

Shift work and breast cancer among women textile workers in Shanghai, China.

PubMed

Li, Wenjin; Ray, Roberta M; Thomas, David B; Davis, Scott; Yost, Michael; Breslow, Norman; Gao, Dao Li; Fitzgibbons, E Dawn; Camp, Janice E; Wong, Eva; Wernli, Karen J; Checkoway, Harvey

2015-01-01

Although night-shift work has been associated with elevated risk of breast cancer in numerous epidemiologic studies, evidence is not consistent. We conducted a nested case-cohort study to investigate a possible association between shift work including a night shift and risk of breast cancer within a large cohort of women textile workers in Shanghai, China. The study included 1,709 incident breast cancer cases and 4,780 non-cases. Data on historical shift work schedules were collected by categorized jobs from the factories, where the study subjects had worked, and then were linked to the complete work histories of each subject. No jobs in the factories involved exclusively night-shift work. Therefore, night shift was evaluated as part of a rotating shift work pattern. Hazard ratios and 95 % confidence intervals were calculated using Cox proportional hazards modeling adapted for the case-cohort design for years of night-shift work and the total number of nights worked. Additionally, analyses were repeated with exposures lagged by 10 and 20 years. We observed no associations with either years of night-shift work or number of nights worked during the entire employment period, irrespective of lag intervals. Findings from the age-stratified analyses were very similar to those observed for the entire study population. The findings from this study provide no evidence to support the hypothesis that shift work increases breast cancer risk. The positive association between shift work and breast cancer observed in Western populations, but not observed in this and other studies of the Chinese population, suggests that the effect of shift work on breast cancer risk may be different in Asian and Caucasian women.

Validation of the DRAGON score in 12 stroke centers in anterior and posterior circulation.

PubMed

Strbian, Daniel; Seiffge, David J; Breuer, Lorenz; Numminen, Heikki; Michel, Patrik; Meretoja, Atte; Coote, Skye; Bordet, Régis; Obach, Victor; Weder, Bruno; Jung, Simon; Caso, Valeria; Curtze, Sami; Ollikainen, Jyrki; Lyrer, Philippe A; Eskandari, Ashraf; Mattle, Heinrich P; Chamorro, Angel; Leys, Didier; Bladin, Christopher; Davis, Stephen M; Köhrmann, Martin; Engelter, Stefan T; Tatlisumak, Turgut

2013-10-01

The DRAGON score predicts functional outcome in the hyperacute phase of intravenous thrombolysis treatment of ischemic stroke patients. We aimed to validate the score in a large multicenter cohort in anterior and posterior circulation. Prospectively collected data of consecutive ischemic stroke patients who received intravenous thrombolysis in 12 stroke centers were merged (n=5471). We excluded patients lacking data necessary to calculate the score and patients with missing 3-month modified Rankin scale scores. The final cohort comprised 4519 eligible patients. We assessed the performance of the DRAGON score with area under the receiver operating characteristic curve in the whole cohort for both good (modified Rankin scale score, 0-2) and miserable (modified Rankin scale score, 5-6) outcomes. Area under the receiver operating characteristic curve was 0.84 (0.82-0.85) for miserable outcome and 0.82 (0.80-0.83) for good outcome. Proportions of patients with good outcome were 96%, 93%, 78%, and 0% for 0 to 1, 2, 3, and 8 to 10 score points, respectively. Proportions of patients with miserable outcome were 0%, 2%, 4%, 89%, and 97% for 0 to 1, 2, 3, 8, and 9 to 10 points, respectively. When tested separately for anterior and posterior circulation, there was no difference in performance (P=0.55); areas under the receiver operating characteristic curve were 0.84 (0.83-0.86) and 0.82 (0.78-0.87), respectively. No sex-related difference in performance was observed (P=0.25). The DRAGON score showed very good performance in the large merged cohort in both anterior and posterior circulation strokes. The DRAGON score provides rapid estimation of patient prognosis and supports clinical decision-making in the hyperacute phase of stroke care (eg, when invasive add-on strategies are considered).

Chocolate intake and incidence of heart failure: Findings from the Cohort of Swedish Men.

PubMed

Steinhaus, Daniel A; Mostofsky, Elizabeth; Levitan, Emily B; Dorans, Kirsten S; Håkansson, Niclas; Wolk, Alicja; Mittleman, Murray A

2017-01-01

The objective of this study was to evaluate the association of chocolate consumption and heart failure (HF) in a large population of Swedish men. We conducted a prospective cohort study of 31,917 men 45-79 years old with no history of myocardial infarction, diabetes, or HF at baseline who were participants in the population-based Cohort of Swedish Men study. Chocolate consumption was assessed through a self-administrated food frequency questionnaire. Participants were followed for HF hospitalization or mortality from January 1, 1998, to December 31, 2011, using record linkage to the Swedish inpatient and cause-of-death registries. During 14 years of follow-up, 2,157 men were hospitalized (n=1,901) or died from incident HF (n=256). Compared with subjects who reported no chocolate intake, the multivariable-adjusted rate ratio of HF was 0.88 (95% CI 0.78-0.99) for those consuming 1-3 servings per month, 0.83 (95% CI 0.72-0.94) for those consuming 1-2 servings per week, 0.82 (95% CI 0.68-0.99) for those consuming 3-6 servings per week, and 1.10 (95% CI 0.84-1.45) for those consuming ≥1 serving per day (P for quadratic trend=.001). In this large prospective cohort study, there was a J-shaped relationship between chocolate consumption and HF incidence. Moderate chocolate consumption was associated with a lower rate of HF hospitalization or death, but the protective association was not observed among individuals consuming ≥1 serving per day. Journal Subject Codes: Etiology: Epidemiology, Heart failure: Congestive. Copyright © 2016 Elsevier Inc. All rights reserved.

Predictors of weight loss in early treated Parkinson's disease from the NET-PD LS-1 cohort.

PubMed

Wills, Anne-Marie; Li, Ruosha; Pérez, Adriana; Ren, Xuehan; Boyd, James

2017-08-01

Weight loss is a common symptom of Parkinson's disease and is associated with impaired quality of life. Predictors of weight loss have not been studied in large clinical cohorts. We previously observed an association between change in body mass index and change in Unified Parkinson's Disease Rating Scale (UPDRS) motor and total scores. In this study, we performed a secondary analysis of longitudinal data (1-6 years) from 1619 participants in the NINDS Exploratory Trials in PD Long-term Study-1 (NET-PD LS1) to explore predictors of weight loss in a large prospective clinical trial cohort of early treated Parkinson's disease. The NET-PD LS1 study was a double-blind randomized placebo controlled clinical trial of creatine monohydrate 10 gm/day in early treated PD (within 5 years of diagnosis and within 2 years of starting dopaminergic medications). Linear mixed models were used to estimate the effect of baseline clinical covariates on weight change over time. On average, participants lost only 0.6 kg per year. Higher age, baseline weight, female gender, higher baseline UPDRS scores, greater postural instability, difficulty eating and drinking, lower cognitive scores and baseline levodopa use (compared to dopamine agonists) were all associated with weight loss. Surprisingly baseline difficulty swallowing, dyskinesia, depression, intestinal hypomotility (constipation) and self-reported nausea/vomiting/anorexia were not significantly associated with weight loss in this cohort of early treated Parkinson's disease patients. On average, participants with Parkinson's disease experience little weight loss during the first 1-6 years after starting dopaminergic replacement therapy, however levodopa use and postural instability were both predictors of early weight loss. Trial Registration clinicaltrials.gov identifier# NCT00449865.

Time-trends in the prescribing of gastroprotective agents to primary care patients initiating low-dose aspirin or non-steroidal anti-inflammatory drugs: a population-based cohort study

PubMed Central

Warlé-van Herwaarden, Margaretha F; Koffeman, Aafke R; Valkhoff, Vera E; ’t Jong, Geert W; Kramers, Cornelis; Sturkenboom, Miriam C; De Smet, Peter A G M

2015-01-01

Aims Low-dose aspirin (LDA) and non-steroidal-anti-inflammatory drugs (NSAIDs) both increase the risk of upper gastrointestinal events (UGIEs). In the Netherlands, recommendations regarding the prescription of gastroprotective agents (GPAs) in LDA users were first issued in 2009 in the HARM-Wrestling consensus. National guidelines on gastroprotective strategies (GPSs) in NSAID users were issued in the first part of the preceding. The aim of the present study was to examine time-trends in GPSs in patients initiating LDA and those initiating NSAIDs between 2000 and 2012. Methods Within a large electronic primary healthcare database, two cohorts were selected: (i) patients newly prescribed LDA and (ii) patients newly prescribed NSAIDs between 2000 and 2012. Patients who had been prescribed a GPA in the previous six months were excluded. For both cohorts, patients’ risk of a UGIE was classified as low, moderate or high, based on the HARM-Wrestling consensus, and the presence of an adequate GPSwas determined. Results A total of 37 578 patients were included in the LDA cohort and 352 025 patients in the NSAID cohort. In both cohorts, an increase in GPSs was observed over time, but prescription of GPAs was lower in the LDA cohort. By 2012, an adequate GPS was present in 31.8% of high-risk LDA initiators, vs. 48.0% of high-risk NSAID initiators. Conclusions Despite a comparable risk of UGIEs, GPSs are prescribed less in high-risk LDA initiators than in high-risk NSAID initiators. For both groups of patients, there is still room for improvement in guideline adherence. PMID:25777983

Time-trends in the prescribing of gastroprotective agents to primary care patients initiating low-dose aspirin or non-steroidal anti-inflammatory drugs: a population-based cohort study.

PubMed

Warlé-van Herwaarden, Margaretha F; Koffeman, Aafke R; Valkhoff, Vera E; 't Jong, Geert W; Kramers, Cornelis; Sturkenboom, Miriam C; De Smet, Peter A G M

2015-09-01

Low-dose aspirin (LDA) and non-steroidal-anti-inflammatory drugs (NSAIDs) both increase the risk of upper gastrointestinal events (UGIEs). In the Netherlands, recommendations regarding the prescription of gastroprotective agents (GPAs) in LDA users were first issued in 2009 in the HARM-Wrestling consensus. National guidelines on gastroprotective strategies (GPSs) in NSAID users were issued in the first part of the preceding. The aim of the present study was to examine time-trends in GPSs in patients initiating LDA and those initiating NSAIDs between 2000 and 2012. Within a large electronic primary healthcare database, two cohorts were selected: (i) patients newly prescribed LDA and (ii) patients newly prescribed NSAIDs between 2000 and 2012. Patients who had been prescribed a GPA in the previous six months were excluded. For both cohorts, patients' risk of a UGIE was classified as low, moderate or high, based on the HARM-Wrestling consensus, and the presence of an adequate GPSwas determined. A total of 37 578 patients were included in the LDA cohort and 352 025 patients in the NSAID cohort. In both cohorts, an increase in GPSs was observed over time, but prescription of GPAs was lower in the LDA cohort. By 2012, an adequate GPS was present in 31.8% of high-risk LDA initiators, vs. 48.0% of high-risk NSAID initiators. Despite a comparable risk of UGIEs, GPSs are prescribed less in high-risk LDA initiators than in high-risk NSAID initiators. For both groups of patients, there is still room for improvement in guideline adherence. © 2015 The British Pharmacological Society.

The course of PTSD in naturalistic long-term studies: high variability of outcomes. A systematic review.

PubMed

Steinert, Christiane; Hofmann, Mareike; Leichsenring, Falk; Kruse, Johannes

2015-01-01

With a lifetime prevalence of 8% posttraumatic stress disorder (PTSD) is one of the most common mental disorders; nevertheless, its longitudinal course is largely unknown. Our aim was to conduct a systematic review summarizing available findings on the prospective, naturalistic long-term course of PTSD and its predictors. Databases MEDLINE and PsycINFO were searched. Main selection criteria were: 1) naturalistic cohort study with a follow-up period of at least 3 years, 2) adult participants with observer-rated or probable PTSD at baseline. Twenty-four cohorts (25 studies) were retrieved (14 with observer-assessed, 10 with probable PTSD). In total, they comprised about 10,500 participants with PTSD at baseline that were included in the long-term follow-ups. Studies investigating patient populations with observer-assessed PTSD found that between 18% and 50% of patients experienced a stable recovery within 3-7 years; the remaining subjects either facing a recurrent or a more chronic course. Outcomes of community studies and studies investigating probable PTSD varied considerably (remission rates 6-92%). Social factors (e.g. support) as well as comorbid physical or mental health problems seem to be salient predictors of PTSD long-term course and special focus should be laid on these factors in clinical settings. Included studies differed notably with regard to applied methodologies. The resulting large variability of findings is discussed. More standardized systematic follow-up research and more uniformed criteria for remission and chronicity are needed to gain a better insight into the long-term course of PTSD.

When bigger is not better: selection against large size, high condition and fast growth in juvenile lemon sharks.

PubMed

Dibattista, J D; Feldheim, K A; Gruber, S H; Hendry, A P

2007-01-01

Selection acting on large marine vertebrates may be qualitatively different from that acting on terrestrial or freshwater organisms, but logistical constraints have thus far precluded selection estimates for the former. We overcame these constraints by exhaustively sampling and repeatedly recapturing individuals in six cohorts of juvenile lemon sharks (450 age-0 and 255 age-1 fish) at an enclosed nursery site (Bimini, Bahamas). Data on individual size, condition factor, growth rate and inter-annual survival were used to test the 'bigger is better', 'fatter is better' and 'faster is better' hypotheses of life-history theory. For age-0 sharks, selection on all measured traits was weak, and generally acted against large size and high condition. For age-1 sharks, selection was much stronger, and consistently acted against large size and fast growth. These results suggest that selective pressures at Bimini may be constraining the evolution of large size and fast growth, an observation that fits well with the observed small size and low growth rate of juveniles at this site. Our results support those of some other recent studies in suggesting that bigger/fatter/faster is not always better, and may often be worse.

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.

Real-world Canagliflozin Utilization: Glycemic Control Among Patients With Type 2 Diabetes Mellitus-A Multi-Database Synthesis.

PubMed

Chow, Wing; Miyasato, Gavin; Kokkotos, Fotios K; Bailey, Robert A; Buysman, Erin K; Henk, Henry J

2016-09-01

Randomized controlled trials have found that treatment of type 2 diabetes mellitus with canagliflozin, a sodium glucose co-transporter 2 inhibitor, is associated with significant reductions in glycosylated hemoglobin (HbA1c) levels. However, very few studies have evaluated the effectiveness of sodium glucose co-transporter 2 inhibitors in a real-world context. This data synthesis aims to examine the demographic characteristics and glycemic control among patients treated with canagliflozin in clinical practice, using results obtained from 2 US-specific retrospective administrative claims databases. Data included in the synthesis were derived from 2 large claims databases (the Optum Research Database and the Inovalon MORE(2) Registry, Research Edition) and were obtained from 3 recently published retrospective observational studies of adult patients with type 2 diabetes mellitus who were treated with canagliflozin. Two of the studies used the Optum database (3-month and 6-month follow-up) and 1 study used the Inovalon database (mean follow-up of 4 months). Patient demographic characteristics, clinical characteristics, treatment utilization, and achievement of glycemic goals at baseline and after canagliflozin treatment were evaluated across the 3 studies. Results were assessed using univariate descriptive statistics. Baseline demographic characteristics were generally similar between the Optum and Inovalon cohorts. Mean baseline HbA1c was 8.7% in the Optum and 8.3% in the Inovalon cohort. Seventy-five percent of the Optum (3-month study) cohort and 74% of the Inovalon cohort used 2 or more antihyperglycemic agents. During follow-up, in both cohorts, the proportion of patients who achieved tight glycemic control (HbA1c <7.0%) more than doubled, while the proportion who had poor control (HbA1c ≥9.0%) decreased by approximately 50%. Among patients who had baseline HbA1c ≥7.0%, 21% of the Optum cohort and 24% of the Inovalon cohort achieved tight glycemic control (HbA1c <7.0%), and the proportion of patients achieving HbA1c <8.0% more than doubled in both cohorts (from 30% to 61% in the Optum cohort, and from 33% to 69% in the Inovalon cohort). This synthesis of real-world data from 2 large patient databases suggests that treatment of type 2 diabetes mellitus with canagliflozin is associated with significant and consistent improvements in glycemic control. Patients with varying HbA1c control and multiple antihyperglycemic agent use were able to lower their HbA1c levels with canagliflozin treatment. Additional studies with longer follow-up would be beneficial to evaluate the durability of the real-world effectiveness of canagliflozin. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

Utilisation and Safety of Deferasirox: Results from an Observational Cohort Study in England.

PubMed

Osborne, Vicki; Davies, Miranda; Layton, Deborah; Shakir, Saad A W

2018-03-01

Deferasirox (EXJADE ® , Novartis, UK) is an oral iron-chelating agent primarily used to reduce chronic iron overload in patients receiving blood transfusions for various chronic anaemias and some non-transfusion dependant anaemias. The aim of this study was to examine the utilisation and safety of deferasirox used in general practice in England. A single exposure observational cohort study design was used. Patients were identified from dispensed prescriptions for deferasirox between September 2006 and September 2014. Outcome data were collected via postal questionnaires sent to prescribers ≥ 6 months after first dispensed prescription for an individual patient. Summary descriptive statistics were calculated. The evaluable cohort consisted of 122 patients, of which 41.8% were aged 2-17 years. Frequent reasons for prescribing were sickle cell anaemia (27/103 where specified, 26.2%) and beta thalassaemia (26, 25.2%). The majority of patients (43/51, 84.3%) were prescribed the licensed doses of 10 or 20 mg/kg/day at start. Prior measurements of serum creatinine were only reported for a small proportion this study (18/122, 14.8%). In total, 91 incident events were reported, including two of raised serum creatinine. These results show that deferasirox is largely being prescribed for its licensed indications in general practice in England and events reported were consistent with the known safety profile.

Effects of high CD4 cell counts on death and attrition among HIV patients receiving antiretroviral treatment: an observational cohort study.

PubMed

Tang, Zhenzhu; Pan, Stephen W; Ruan, Yuhua; Liu, Xuanhua; Su, Jinming; Zhu, Qiuying; Shen, Zhiyong; Zhang, Heng; Chen, Yi; Lan, Guanghua; Xing, Hui; Liao, Lingjie; Feng, Yi; Shao, Yiming

2017-06-09

Current WHO guidelines recommend initiating ART regardless of CD4+ cell count. In response, we conducted an observational cohort study to assess the effects of pre-ART CD4+ cell count levels on death, attrition, and death or attrition in HIV treated patients. This large HIV treatment cohort study (n = 49,155) from 2010 to 2015 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between pre-ART CD4+ cell counts and death, attrition, and death or attrition. The average mortality and ART attrition rates among all treated patients were 2.63 deaths and 5.32 attritions per 100 person-years, respectively. Compared to HIV patients with <350 CD4+ cells/mm 3 at ART initiation, HIV patients with >500 CD4+ cells/mm 3 at ART initiation had a significantly lower mortality rate (Adjusted hazard ratio: 0.56, 95% CI: 0.40-0.79), but significantly higher ART attrition rate (AHR: 1.17, 95% CI: 1.03-1.33). Results from this study suggest that HIV patients with high CD4+ cell counts at the time of ART initiation may be at greater risk of treatment attrition. To further reduce ART attrition, it is imperative that patient education and healthcare provider training on ART adherence be enhanced and account for CD4 levels at ART initiation.

Early Detection of Increased Intracranial Pressure Episodes in Traumatic Brain Injury: External Validation in an Adult and in a Pediatric Cohort.

PubMed

Güiza, Fabian; Depreitere, Bart; Piper, Ian; Citerio, Giuseppe; Jorens, Philippe G; Maas, Andrew; Schuhmann, Martin U; Lo, Tsz-Yan Milly; Donald, Rob; Jones, Patricia; Maier, Gottlieb; Van den Berghe, Greet; Meyfroidt, Geert

2017-03-01

A model for early detection of episodes of increased intracranial pressure in traumatic brain injury patients has been previously developed and validated based on retrospective adult patient data from the multicenter Brain-IT database. The purpose of the present study is to validate this early detection model in different cohorts of recently treated adult and pediatric traumatic brain injury patients. Prognostic modeling. Noninterventional, observational, retrospective study. The adult validation cohort comprised recent traumatic brain injury patients from San Gerardo Hospital in Monza (n = 50), Leuven University Hospital (n = 26), Antwerp University Hospital (n = 19), Tübingen University Hospital (n = 18), and Southern General Hospital in Glasgow (n = 8). The pediatric validation cohort comprised patients from neurosurgical and intensive care centers in Edinburgh and Newcastle (n = 79). None. The model's performance was evaluated with respect to discrimination, calibration, overall performance, and clinical usefulness. In the recent adult validation cohort, the model retained excellent performance as in the original study. In the pediatric validation cohort, the model retained good discrimination and a positive net benefit, albeit with a performance drop in the remaining criteria. The obtained external validation results confirm the robustness of the model to predict future increased intracranial pressure events 30 minutes in advance, in adult and pediatric traumatic brain injury patients. These results are a large step toward an early warning system for increased intracranial pressure that can be generally applied. Furthermore, the sparseness of this model that uses only two routinely monitored signals as inputs (intracranial pressure and mean arterial blood pressure) is an additional asset.

Occupational stress and incidence of sick leave in the Belgian workforce: the Belstress study

PubMed Central

Moreau, M; Valente, F; Mak, R; Pelfrene, E; de Smet, P; De Backer, G; Kornitzer, M

2004-01-01

Context: Sick leave is a major problem in public health. The Karasek demands/control/social support/strain (JDCS) model has been largely used to predict a wide range of health outcomes and to a lesser extent sickness absence. Study objective: The aim of the study was to test the predictive power of the JDCS model in relation with one year incidence of sick leave in a large cohort of workers. Design and setting: Cohort study conducted between 1994 and 1998 in 25 companies across Belgium. Participants: A total of 20 463 workers aged 35 to 59 years were followed up for sick leave during one year after the baseline survey. Outcomes: The outcomes were a high sick leave incidence, short spells (⩾7 days), long spells (⩾28 days), and repetitive spells of sickness absence (⩾3 spells/year). Main results: Independently from baseline confounding variables, a significant association between high strained jobs with low social support and repetitive spells of sickness absence was observed in both sexes with odds ratios of 1.32 (99% CI, 1.04 to 1.68) in men and 1.61 (99% CI, 1.13 to 2.33) in women. In men, high strained jobs with low social support was also significantly associated with high sick leave incidence, and short spells of sick leave with odds ratios of 1.38 (99% CI, 1.16 to 1.64) and 1.22 (99% CI, 1.05 to 1.44) respectively. Conclusions: Perceived high strain at work especially combined with low social support is predictive of sick leave in both sexes of a large cohort of the Belgian workforce. PMID:15143121

Bayesian networks: a new method for the modeling of bibliographic knowledge: application to fall risk assessment in geriatric patients.

PubMed

Lalande, Laure; Bourguignon, Laurent; Carlier, Chloé; Ducher, Michel

2013-06-01

Falls in geriatry are associated with important morbidity, mortality and high healthcare costs. Because of the large number of variables related to the risk of falling, determining patients at risk is a difficult challenge. The aim of this work was to validate a tool to detect patients with high risk of fall using only bibliographic knowledge. Thirty articles corresponding to 160 studies were used to modelize fall risk. A retrospective case-control cohort including 288 patients (88 ± 7 years) and a prospective cohort including 106 patients (89 ± 6 years) from two geriatric hospitals were used to validate the performances of our model. We identified 26 variables associated with an increased risk of fall. These variables were split into illnesses, medications, and environment. The combination of the three associated scores gives a global fall score. The sensitivity and the specificity were 31.4, 81.6, 38.5, and 90 %, respectively, for the retrospective and the prospective cohort. The performances of the model are similar to results observed with already existing prediction tools using model adjustment to data from numerous cohort studies. This work demonstrates that knowledge from the literature can be synthesized with Bayesian networks.

Does Educational Status Impact Adult Mortality in Denmark? A Twin Approach

PubMed Central

Madsen, Mia; Andersen, Anne-Marie Nybo; Christensen, Kaare; Andersen, Per Kragh; Osler, Merete

2010-01-01

To disentangle an independent effect of educational status on mortality risk from direct and indirect selection mechanisms, the authors used a discordant twin pair design, which allowed them to isolate the effect of education by means of adjustment for genetic and environmental confounding per design. The study is based on data from the Danish Twin Registry and Statistics Denmark. Using Cox regression, they estimated hazard ratios for mortality according to the highest attained education among 5,260 monozygotic and 11,088 dizygotic same-sex twin pairs born during 1921–1950 and followed during 1980–2008. Both standard cohort and intrapair analyses were conducted separately for zygosity, gender, and birth cohort. Educational differences in mortality were demonstrated in the standard cohort analyses but attenuated in the intrapair analyses in all subgroups but men born during 1921–1935, and no effect modification by zygosity was observed. Hence, the results are most compatible with an effect of early family environment in explaining the educational inequality in mortality. However, large educational differences were still reflected in mortality risk differences within twin pairs, thus supporting some degree of independent effect of education. In addition, the effect of education may be more pronounced in older cohorts of Danish men. PMID:20530466

Birth cohorts in Asia: The importance, advantages, and disadvantages of different-sized cohorts.

PubMed

Kishi, Reiko; Araki, Atsuko; Minatoya, Machiko; Itoh, Sachiko; Goudarzi, Houman; Miyashita, Chihiro

2018-02-15

Asia contains half of the world's children, and the countries of Asia are the most rapidly industrializing nations on the globe. Environmental threats to the health of children in Asia are myriad. Several birth cohorts were started in Asia in early 2000, and currently more than 30 cohorts in 13 countries have been established for study. Cohorts can contain from approximately 100-200 to 20,000-30,000 participants. Furthermore, national cohorts targeting over 100,000 participants have been launched in Japan and Korea. The aim of this manuscript is to discuss the importance of Asian cohorts, and the advantages and disadvantages of different-sized cohorts. As for case, one small-sized (n=514) cohort indicate that even relatively low level exposure to dioxin in utero could alter birth size, neurodevelopment, and immune and hormonal functions. Several Asian cohorts focus prenatal exposure to perfluoroalkyo substances and reported associations with birth size, thyroid hormone levels, allergies and neurodevelopment. Inconsistent findings may possibly be explained by the differences in exposure levels and target chemicals, and by possible statistical errors. In a smaller cohort, novel hypotheses or preliminary examinations are more easily verifiable. In larger cohorts, the etiology of rare diseases, such as birth defects, can be analyzed; however, they require a large cost and significant human resources. Therefore, conducting studies in only one large cohort may not always be the best strategy. International collaborations, such as the Birth Cohort Consortium of Asia, would cover the inherent limitation of sample size in addition to heterogeneity of exposure, ethnicity, and socioeconomic conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Digital or Didactic: Using Learning Technology to Confront the Challenge of Large Cohort Teaching

ERIC Educational Resources Information Center

Saunders, Fiona C.; Gale, Andrew W.

2012-01-01

This paper investigates whether the selective use of technology can begin to overcome the challenge of large cohort teaching and deliver an enhanced student learning experience. It describes the initial development and evaluation of a campus-based management course taught to 270 third year engineering undergraduates at The University of…

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.

How Many Is Too Many? On the Relationship between Research Productivity and Impact

PubMed Central

Larivière, Vincent; Costas, Rodrigo

2016-01-01

Over the last few decades, the institutionalisation of quantitative research evaluations has created incentives for scholars to publish as many papers as possible. This paper assesses the effects of such incentives on individual researchers’ scientific impact, by analysing the relationship between their number of articles and their proportion of highly cited papers. In other words, does the share of an author’s top 1% most cited papers increase, remain stable, or decrease as his/her total number of papers increase? Using a large dataset of disambiguated researchers (N = 28,078,476) over the 1980–2013 period, this paper shows that, on average, the higher the number of papers a researcher publishes, the higher the proportion of these papers are amongst the most cited. This relationship is stronger for older cohorts of researchers, while decreasing returns to scale are observed for recent cohorts. On the whole, these results suggest that for established researchers, the strategy of publishing as many papers as possible did not yield lower shares of highly cited publications, but such a pattern is not always observed for younger scholars. PMID:27682366

ABO blood group and risk of cancer: A register-based cohort study of 1.6 million blood donors.

PubMed

Vasan, Senthil K; Hwang, Jinseub; Rostgaard, Klaus; Nyrén, Olof; Ullum, Henrik; Pedersen, Ole B V; Erikstrup, Christian; Melbye, Mads; Hjalgrim, Henrik; Pawitan, Yudi; Edgren, Gustaf

2016-10-01

The associations between ABO blood group and cancer risk have been studied repeatedly, but results have been variable. Consistent associations have only been reported for pancreatic and gastric cancers. We estimated associations between different ABO blood groups and site-specific cancer risk in a large cohort of healthy blood donors from Sweden and Denmark. A total of 1.6 million donors were followed over 27 million person-years (20 million in Sweden and 7 million in Denmark). We observed 119,584 cancer cases. Blood groups A, AB and B were associated either with increased or decreased risk of cancer at 13 anatomical sites (p≤0.05), compared to blood group O. Consistent with assessment using a false discovery rate approach, significant associations with ABO blood group were observed for cancer of the pancreas, breast, and upper gastrointestinal tract (mouth, salivary glands, pharynx, esophageal adenocarcinoma and stomach). Our study reconfirms the association between ABO blood group and cancer risk and exact underlying mechanisms involved needs further research. Copyright © 2016 Elsevier Ltd. All rights reserved.

No association of dynamin binding protein (DNMBP) gene SNPs and Alzheimer's disease.

PubMed

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

2008-10-01

A recent scan of single nucleotide polymorphisms (SNPs) on chromosome 10q found significant association of six correlated SNPs with late-onset Alzheimer's disease (AD) among Japanese. We examined the SNP with the highest statistical significance (rs3740058) in a large Caucasian American case-control cohort and the remaining five SNPs in a smaller subset of cases and controls. We observed no association of statistical significance in either the total sample or the APOE*4 non-carriers for any of the SNPs.

Transiting Exoplanet Survey Satellite (TESS)

NASA Technical Reports Server (NTRS)

Ricker, G. R.; Clampin, M.; Latham, D. W.; Seager, S.; Vanderspek, R. K.; Villasenor, J. S.; Winn, J. N.

2012-01-01

The Transiting Exoplanet Survey Satellite (TESS) will discover thousands of exoplanets in orbit around the brightest stars in the sky. In a two-year survey, TESS will monitor more than 500,000 stars for temporary drops in brightness caused by planetary transits. This first-ever spaceborne all-sky transit survey will identify planets ranging from Earth-sized to gas giants, around a wide range of stellar types and orbital distances. No ground-based survey can achieve this feat. A large fraction of TESS target stars will be 30-100 times brighter than those observed by Kepler satellite, and therefore TESS . planets will be far easier to characterize with follow-up observations. TESS will make it possible to study the masses, sizes, densities, orbits, and atmospheres of a large cohort of small planets, including a sample of rocky worlds in the habitable zones of their host stars. TESS will provide prime targets for observation with the James Webb Space Telescope (JWST), as well as other large ground-based and space-based telescopes of the future. TESS data will be released with minimal delay (no proprietary period), inviting immediate community-wide efforts to study the new planets. The TESS legacy will be a catalog of the very nearest and brightest main-sequence stars hosting transiting exoplanets, thus providing future observers with the most favorable targets for detailed investigations.

Health Impact of US Military Service in a Large Population-Based Military Cohort: Findings of the Millennium Cohort Study, 2001-2008

DTIC Science & Technology

2011-01-01

427. 26. Smith TC, Wingard DL, Ryan MA, Kritz- Silverstein D, Slymen DJ, Sallis JF, for the Millennium Cohort Study Team: Prior assault and... Silverstein D, for the Millennium Cohort Study Team: New onset and persistent symptoms of post- traumatic stress disorder self reported after deployment...deployed to the 2003 Iraq war: a cohort study. Lancet 2006, 367(9524):1731-1741. 41. Smith TC, Wingard DL, Ryan MAK, Kritz- Silverstein D, Slymen DJ, Sallis

Trends in Hip Fracture Rates in Canada: An Age-Period-Cohort Analysis

PubMed Central

Jean, Sonia; O’Donnell, Siobhan; Lagacé, Claudia; Walsh, Peter; Bancej, Christina; Brown, Jacques P.; Morin, Suzanne; Papaioannou, Alexandra; Jaglal, Susan B.; Leslie, William D.

2016-01-01

Age-standardized rates of hip fracture in Canada declined during the period 1985 to 2005. We investigated whether this incidence pattern is explained by period effects, cohort effects, or both. All hospitalizations during the study period with primary diagnosis of hip fracture were identified. Age- and sex-specific hip fracture rates were calculated for nineteen 5-year age groups and four 5-year calendar periods, resulting in 20 birth cohorts. The effect of age, calendar period, and birth cohort on hip fracture rates was assessed using age-period-cohort models as proposed by Clayton and Schiffers. From 1985 to 2005, a total of 570,872 hospitalizations for hip fracture were identified. Age-standardized rates for hip fracture have progressively declined for females and males. The annual linear decrease in rates per 5-year period were 12% for females and 7% for males (both p < 0.0001). Significant birth cohort effects were also observed for both sexes (p < 0.0001). Cohorts born before 1950 had a higher risk of hip fracture, whereas those born after 1954 had a lower risk. After adjusting for age and constant annual linear change (drift term common to both period and cohort effects), we observed a significant nonlinear birth cohort effect for males (p = 0.0126) but not for females (p = 0.9960). In contrast, the nonlinear period effect, after adjustment for age and drift term, was significant for females (p = 0.0373) but not for males (p = 0.2515). For males, we observed no additional nonlinear period effect after adjusting for age and birth cohort, whereas for females, we observed no additional nonlinear birth cohort effect after adjusting for age and period. Although hip fracture rates decreased in both sexes, different factors may explain these changes. In addition to the constant annual linear decrease, nonlinear birth cohort effects were identified for males, and calendar period effects were identified for females as possible explanations. PMID:23426882

Methods of epidemiology: evaluating the fat-breast cancer hypothesis--comparing dietary instruments and other developments.

PubMed

Freedman, Laurence S; Kipnis, Victor; Schatzkin, Arthur; Potischman, Nancy

2008-01-01

Results from several large cohort studies that were reported 10 to 20 years ago seemed to indicate that the hypothesized link between dietary fat intake and breast cancer risk was illusory. In this article, we review several strands of more recent evidence that have emerged. These include two studies comparing the performance of dietary instruments used to investigate the dietary fat- breast cancer hypothesis, a large randomized disease prevention trial, a more recent meta-analysis of nutritional cohort studies, and a very large nutritional cohort study. Each of the studies discussed in this article suggests that a modest but real association between fat intake and breast cancer is likely. If the association is causative, it would have important implications for public health strategies in reducing breast cancer incidence. The evidence is not yet conclusive, but additional follow-up in the randomized trial, as well as efforts to improve dietary assessment methodology for cohort studies, may be sufficient to provide a convincing answer.

A review of epidemiological data on epilepsy, phenobarbital, and risk of liver cancer.

PubMed

La Vecchia, Carlo; Negri, Eva

2014-01-01

Phenobarbital is not genotoxic, but has been related to promotion of liver cancer (as well as inhibition) in rodents. In October 2012, we carried out a systematic literature search in the Medline database and searched reference lists of retrieved publications. We identified 15 relevant papers. Epidemiological data on epileptics/anticonvulsant use and liver cancer were retrieved from eight reports from seven cohort (record linkage) studies of epileptics, and data on phenobarbital use from a pharmacy-based record linkage investigation of patients treated with phenobarbital (three reports), plus a case-control study nested in one of the cohort studies and including information on phenobarbital use. Of the studies of cancer in epileptics, two showed no excess risk of liver cancer. A long-term (1933-1984) Danish cohort study of epileptics found relative risks (RRs) of 4.7 [95% confidence interval (CI) 3.2-6.8] of liver cancer and of 2.2 (95% CI 1.2-3.5) of biliary tract cancers. Such apparent excess risks could, however, be largely or completely attributed to thorotrast, a contrast medium used in the past in epileptic patients for cerebral angiography. A Finnish cohort study of epileptics obtained an RR of 1.7 (95% CI 1.2-2.4). Such an apparent excess risk, however, was not related to phenobarbital or to any specific anticonvulsant drug. The long-term follow-up of two UK cohorts found some excess risk of liver cancer among severe, but not among mild, epileptics. Some excess risk of liver cancer was also found in cohort studies of patients hospitalized for epilepsy in Sweden and Taiwan, in the absence, however, of association with any specific drugs. A UK General Practice database, comparing epileptics treated with valproate with unexposed ones, found a very low incidence of liver cancer. Of the studies of cancer in patients treated with phenobarbital, a large US pharmacy-based cohort investigation showed no excess risk of liver cancer. In a case-control study, nested in the Danish cohort of epileptics, no association was observed between phenobarbital and liver cancer among patients who had not received thorotrast (RR=1.0 for liver and 0.8 for biliary tract cancers). Thus, some, although not all, studies reported excess risk of all cancers and liver cancer in severe, but not in milder epileptics. There is no evidence of a specific role of phenobarbital in human liver cancer risk, but data on the topic are limited.

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants

PubMed Central

Lenassi, Eva; Vincent, Ajoy; Li, Zheng; Saihan, Zubin; Coffey, Alison J; Steele-Stallard, Heather B; Moore, Anthony T; Steel, Karen P; Luxon, Linda M; Héon, Elise; Bitner-Glindzicz, Maria; Webster, Andrew R

2015-01-01

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration (‘retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one ‘retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype–phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting. PMID:25649381

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.

Host-Specific Adaptation of HIV-1 Subtype B in the Japanese Population

PubMed Central

Chikata, Takayuki; Carlson, Jonathan M.; Tamura, Yoshiko; Borghan, Mohamed Ali; Naruto, Takuya; Hashimoto, Masao; Murakoshi, Hayato; Le, Anh Q.; Mallal, Simon; John, Mina; Gatanaga, Hiroyuki; Oka, Shinichi; Brumme, Zabrina L.

2014-01-01

ABSTRACT The extent to which HIV-1 clade B strains exhibit population-specific adaptations to host HLA alleles remains incompletely known, in part due to incomplete characterization of HLA-associated HIV-1 polymorphisms (HLA-APs) in different global populations. Moreover, it remains unknown to what extent the same HLA alleles may drive significantly different escape pathways across populations. As the Japanese population exhibits distinctive HLA class I allele distributions, comparative analysis of HLA-APs between HIV-1 clade B-infected Japanese and non-Asian cohorts could shed light on these questions. However, HLA-APs remain incompletely mapped in Japan. In a cohort of 430 treatment-naive Japanese with chronic HIV-1 clade B infection, we identified 284 HLA-APs in Gag, Pol, and Nef using phylogenetically corrected methods. The number of HLA-associated substitutions in Pol, notably those restricted by HLA-B*52:01, was weakly inversely correlated with the plasma viral load (pVL), suggesting that the transmission and persistence of B*52:01-driven Pol mutations could modulate the pVL. Differential selection of HLA-APs between HLA subtype members, including those differing only with respect to substitutions outside the peptide-binding groove, was observed, meriting further investigation as to their mechanisms of selection. Notably, two-thirds of HLA-APs identified in Japan had not been reported in previous studies of predominantly Caucasian cohorts and were attributable to HLA alleles unique to, or enriched in, Japan. We also identified 71 cases where the same HLA allele drove significantly different escape pathways in Japan versus predominantly Caucasian cohorts. Our results underscore the distinct global evolution of HIV-1 clade B as a result of host population-specific cellular immune pressures. IMPORTANCE Cytotoxic T lymphocyte (CTL) escape mutations in HIV-1 are broadly predictable based on the HLA class I alleles expressed by the host. Because HLA allele distributions differ among worldwide populations, the pattern and diversity of HLA-associated escape mutations are likely to be somewhat distinct to each race and region. HLA-associated polymorphisms (HLA-APs) in HIV-1 have previously been identified at the population level in European, North American, Australian, and African cohorts; however, large-scale analyses of HIV-1 clade B-specific HLA-APs in Asians are lacking. Differential intraclade HIV-1 adaptation to global populations can be investigated via comparative analyses of HLA-associated polymorphisms across ethnic groups, but such studies are rare. Here, we identify HLA-APs in a large Japanese HIV-1 clade B cohort using phylogenetically informed methods and observe that the majority of them had not been previously characterized in predominantly Caucasian populations. The results highlight HIV's unique adaptation to cellular immune pressures imposed by different global populations. PMID:24522911

Host-specific adaptation of HIV-1 subtype B in the Japanese population.

PubMed

Chikata, Takayuki; Carlson, Jonathan M; Tamura, Yoshiko; Borghan, Mohamed Ali; Naruto, Takuya; Hashimoto, Masao; Murakoshi, Hayato; Le, Anh Q; Mallal, Simon; John, Mina; Gatanaga, Hiroyuki; Oka, Shinichi; Brumme, Zabrina L; Takiguchi, Masafumi

2014-05-01

The extent to which HIV-1 clade B strains exhibit population-specific adaptations to host HLA alleles remains incompletely known, in part due to incomplete characterization of HLA-associated HIV-1 polymorphisms (HLA-APs) in different global populations. Moreover, it remains unknown to what extent the same HLA alleles may drive significantly different escape pathways across populations. As the Japanese population exhibits distinctive HLA class I allele distributions, comparative analysis of HLA-APs between HIV-1 clade B-infected Japanese and non-Asian cohorts could shed light on these questions. However, HLA-APs remain incompletely mapped in Japan. In a cohort of 430 treatment-naive Japanese with chronic HIV-1 clade B infection, we identified 284 HLA-APs in Gag, Pol, and Nef using phylogenetically corrected methods. The number of HLA-associated substitutions in Pol, notably those restricted by HLA-B*52:01, was weakly inversely correlated with the plasma viral load (pVL), suggesting that the transmission and persistence of B*52:01-driven Pol mutations could modulate the pVL. Differential selection of HLA-APs between HLA subtype members, including those differing only with respect to substitutions outside the peptide-binding groove, was observed, meriting further investigation as to their mechanisms of selection. Notably, two-thirds of HLA-APs identified in Japan had not been reported in previous studies of predominantly Caucasian cohorts and were attributable to HLA alleles unique to, or enriched in, Japan. We also identified 71 cases where the same HLA allele drove significantly different escape pathways in Japan versus predominantly Caucasian cohorts. Our results underscore the distinct global evolution of HIV-1 clade B as a result of host population-specific cellular immune pressures. Cytotoxic T lymphocyte (CTL) escape mutations in HIV-1 are broadly predictable based on the HLA class I alleles expressed by the host. Because HLA allele distributions differ among worldwide populations, the pattern and diversity of HLA-associated escape mutations are likely to be somewhat distinct to each race and region. HLA-associated polymorphisms (HLA-APs) in HIV-1 have previously been identified at the population level in European, North American, Australian, and African cohorts; however, large-scale analyses of HIV-1 clade B-specific HLA-APs in Asians are lacking. Differential intraclade HIV-1 adaptation to global populations can be investigated via comparative analyses of HLA-associated polymorphisms across ethnic groups, but such studies are rare. Here, we identify HLA-APs in a large Japanese HIV-1 clade B cohort using phylogenetically informed methods and observe that the majority of them had not been previously characterized in predominantly Caucasian populations. The results highlight HIV's unique adaptation to cellular immune pressures imposed by different global populations.

[A retrospective cohort study on mortality among silicotic workers in Hong Kong with emphasis on lung cancer].

PubMed

Yu, Ignatius Ts; Tse, Lap Ah; Chi, Chiu-leung; Tze, Wai-wong; Cheuk, Ming-Tam; Alan, Ck-chan

2008-01-01

To investigate the relationship between silica or silicosis and lung cancer in a large cohort of silicotic workers in Hong Kong. All workers with silicosis in Hong Kong diagnosed between 1981 and 1998 were followed up till the end of 1999 to ascertain their vital status and causes of death, using the corresponding mortality rates of Hong Kong males of the same period as external comparison. Standardized mortality ratios (SMR) for lung cancer and other major causes of death were calculated. Person-year method was used. Axelson's indirect method was performed to adjust for the confounding effect of smoking. Penalized smoothing spline (p-spline) models were used to evaluate the exposure-response relationship between silica dust exposure and lung cancer mortality. A total of 2789 newly diagnosed cases of silicosis were included in the cohort, with an overall 24 992.6 person-years of observations. The loss-to-follow-up rate was only 2.9%. Surface construction workers (51%) and underground caisson workers (37%) constituted the major part of the cohort. There were 853 silicotics observed with an average age at death of 63.8 years. The SMR for all causes and all cancers increased significantly. The leading cause of death was non-malignant respiratory diseases. About 86 deaths were from lung cancer, giving a SMR of 1.69 (95% CI: 1.35 approximately 2.09). The risk of lung cancer death among workers in surface construction, underground caisson, and entire cohort was reduced to 1.12 (95% CI: 0.89 approximately 1.38), 1.09 (95% CI: 0.82 approximately 1.42) and 1.56 (95% CI: 0.98 approximately 2.36) respectively, after indirectly adjusting for smoking. from P-spline model did not show a clear exposure-response relationship between silica dust (CDE and MDC) and lung cancer mortality. This cohort study did not show an increased risk of lung cancer mortality among silicotic workers. P-spline model does not support an exposure-response relationship between silica dust exposure and lung cancer mortality.

[Six-month effectiveness and tolerability of pioglitazone in combination with sulfonylureas or metformin for the treatment of type 2 diabetes mellitus].

PubMed

Rodríguez, Angel; Reviriego, Jesús; Polavieja, Pepa; Mesa, Jordi

2008-11-29

Pioglitazone has been reported to improve common cardiovascular risk factors in addition to glycemic control in patients with type 2 diabetes mellitus (T2DM). The changes in cardiovascular risk profile were evaluated comparatively in large cohorts either treated or not with pioglitazone-containing combinations in the current clinical setting within Spain. A nationwide prospective, controlled, observational cohort clinical study was performed in 2294 patients with T2DM who started, at the criterion of the treating physician, oral antihyperglycemic treatment with either pioglitazone plus a sulfonylurea (Pio+SU; n=851), pioglitazone plus metformin (Pio+Met; n=723) or a sulfonylurea plus metformin (SU+Met; n=720) due to inadequate control with previous therapy. Serum cholesterol, blood glucose, hemoglobin A1C, blood pressure and certain anthropometric parameters were measured at baseline and after 6 months of treatment. Serum high density lipoprotein-cholesterol increased in average (mg/dl) 2.08 with Pio+SU, 2.06 with Pio+Met and 0.67 with SU+Met; while triglycerides decreased (mg/dl) 26.6, 30.6 and 17.6 in the same cohorts. Inter-group differences were significant (p<0.001 in both parameters). Total cholesterol decreased significantly more with SU+Met than in the pioglitazone cohorts. Mean fasting plasma glucose and hemoglobin A1C reductions were significantly greater in the pioglitazone cohorts than in the SU+Met cohort: 27.74, 28.94 and 23.46 mg/dl (p=0.012); and 0.80, 0.87 and 0.71% (p=0.016) with Pio+SU, Pio+Met and SU+Met, respectively. Slight, but significant variations of body weight were also registered in the Pio+SU (+1.4 kg) and SU+Met (-0.7 kg) groups. Treatment with pioglitazone was associated with significant improvements of lipid and glycemic parameters that are linked to insulin resistance and cardiovascular risk in patients with T2DM in their routine clinical care. The non-randomised allocation of patients to treatments, inherent to its observational design, is an important limitation of the present study.

The Association of Geographic Coordinates with Mortality in People with Lower and Higher Education and with Mortality Inequalities in Spain.

PubMed

Regidor, Enrique; Reques, Laura; Giráldez-García, Carolina; Miqueleiz, Estrella; Santos, Juana M; Martínez, David; de la Fuente, Luis

2015-01-01

Geographic patterns in total mortality and in mortality by cause of death are widely known to exist in many countries. However, the geographic pattern of inequalities in mortality within these countries is unknown. This study shows mathematically and graphically the geographic pattern of mortality inequalities by education in Spain. Data are from a nation-wide prospective study covering all persons living in Spain's 50 provinces in 2001. Individuals were classified in a cohort of subjects with low education and in another cohort of subjects with high education. Age- and sex-adjusted mortality rate from all causes and from leading causes of death in each cohort and mortality rate ratios in the low versus high education cohort were estimated by geographic coordinates and province. Latitude but not longitude was related to mortality. In subjects with low education, latitude had a U-shaped relation to mortality. In those with high education, mortality from all causes, and from cardiovascular, respiratory and digestive diseases decreased with increasing latitude, whereas cancer mortality increased. The mortality-rate ratio for all-cause death was 1.27 in the southern latitudes, 1.14 in the intermediate latitudes, and 1.20 in the northern latitudes. The mortality rate ratios for the leading causes of death were also higher in the lower and upper latitudes than in the intermediate latitudes. The geographic pattern of the mortality rate ratios is similar to that of the mortality rate in the low-education cohort: the highest magnitude is observed in the southern provinces, intermediate magnitudes in the provinces of the north and those of the Mediterranean east coast, and the lowest magnitude in the central provinces and those in the south of the Western Pyrenees. Mortality inequalities by education in Spain are higher in the south and north of the country and lower in the large region making up the central plateau. This geographic pattern is similar to that observed in mortality in the low-education cohort.

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

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.

A study of mortality patterns at a tyre factory 1951-1985: a reference statistic dilemma.

PubMed

Veys, C A

2004-08-01

The general and cancer mortalities of rubber workers at a large tyre factory were studied in an area of marked regional variation in death rates. Three quinquennial intakes of male rubber workers engaged between January 1946 and December 1960 formed a composite cohort of 6454 men to be followed up. Over 99% were successfully traced by December 1985. The cohort analysis used both national and local rates as reference statistics for several causes. Between 1951 and 1985, a national standardized mortality ratio (SMRN) of 101 for all causes (based on 2556 deaths) was noted, whereas the local standardized mortality ratio (SMRL) was only 79. For all cancers, the figures were 115 (SMRN) and 93 (SMRL), for stomach cancer they were 137 (SMRN) and 84 (SMRL), and for lung cancer they were 121 (SMRN) and 94 (SMRL). No outright excesses against the national norm were observed for other cancers except for larynx, brain and central nervous system and thyroid cancer and the leukaemias. Excesses were statistically significant for cancer of the gallbladder and the bile ducts, for silicotuberculosis (SMRN = 1000) and for the pneumoconioses (SMRN = 706). Deaths from cerebrovascular diseases, chronic bronchitis and emphysema showed statistically significant deficits using either norm. These results from a large factory cohort study of rubber workers, followed for over three decades, demonstrate the marked discrepancy that can result from using only one reference statistic in areas of significant variation in mortality patterns.

Knowledge gaps and research recommendations for essential tremor.

PubMed

Hopfner, Franziska; Haubenberger, Dietrich; Galpern, Wendy R; Gwinn, Katrina; Van't Veer, Ashlee; White, Samantha; Bhatia, Kailash; Adler, Charles H; Eidelberg, David; Ondo, William; Stebbins, Glenn T; Tanner, Caroline M; Helmich, Rick C; Lenz, Fred A; Sillitoe, Roy V; Vaillancourt, David; Vitek, Jerrold L; Louis, Elan D; Shill, Holly A; Frosch, Matthew P; Foroud, Tatiana; Kuhlenbäumer, Gregor; Singleton, Andrew; Testa, Claudia M; Hallett, Mark; Elble, Rodger; Deuschl, Günther

2016-12-01

Essential tremor (ET) is a common cause of significant disability, but its etiologies and pathogenesis are poorly understood. Research has been hampered by the variable definition of ET and by non-standardized research approaches. The National Institute of Neurological Disorders and Stroke (USA) invited experts in ET and related fields to discuss current knowledge, controversies, and gaps in our understanding of ET and to develop recommendations for future research. Discussion focused on phenomenology and phenotypes, therapies and clinical trials, pathophysiology, pathology, and genetics. Across all areas, the need for collaborative and coordinated research on a multinational level was expressed. Standardized data collection using common data elements for genetic, clinical, neurophysiological, and pathological studies was recommended. Large cohorts of patients should be studied prospectively to collect bio-samples, characterize the natural history of the clinical syndrome including patient-oriented outcomes, investigate potential etiologies of various phenotypes, and identify pathophysiological mechanisms. In particular, cellular and system-level mechanisms of tremor oscillations should be elucidated because they may yield effective therapeutic targets and biomarkers. A neuropathology consortium was recommended to standardize postmortem analysis and further characterize neuropathological observations in the cerebellum and elsewhere. Furthermore, genome-wide association studies on large patient cohorts (>10,000 patients) may allow the identification of common genes contributing to risk, and whole exome or genome sequencing may enable the identification of genetic risk and causal mutations in cohorts and well-characterized families. Copyright © 2016 Elsevier Ltd. All rights reserved.

Use of fertility drugs and risk of uterine cancer: results from a large Danish population-based cohort study.

PubMed

Jensen, Allan; Sharif, Heidi; Kjaer, Susanne K

2009-12-01

Some epidemiologic studies have indicated that uterine cancer risk may be increased after use of fertility drugs. To further assess this association, the authors used data from a large cohort of 54,362 women diagnosed with infertility who were referred to Danish fertility clinics between 1965 and 1998. In a case-cohort study, rate ratios and 95% confidence intervals were used to assess the effects of 4 groups of fertility drugs on overall risk of uterine cancer after adjustment for potentially confounding factors. Through mid-2006, 83 uterine cancers were identified. Ever use of any fertility drug was not associated with uterine cancer risk (rate ratio (RR) = 1.10, 95% confidence interval (CI): 0.69, 1.76). However, ever use of gonadotropins (follicle-stimulating hormone and human menopausal gonadotropin) increased uterine cancer risk (RR = 2.21, 95% CI: 1.08, 4.50); the risk was primarily observed after 10 years of follow-up. Furthermore, uterine cancer risk increased with number of cycles of use for clomiphene (for > or =6 cycles, RR = 1.96, 95% CI: 1.03, 3.72) and human chorionic gonadotropin (for > or =6 cycles, RR = 2.18, 95% CI: 1.16, 4.08) but not for other gonadotropins. Use of gonadotropin-releasing hormone analogs was not associated with risk. Gonadotropins, and possibly clomiphene and human chorionic gonadotropin, may increase the risk of uterine cancer, with higher doses and longer follow-up leading to greater risk.

Observational longitudinal cohort study to determine progression to heart failure in a screened community population: the Echocardiographic Heart of England Screening Extension (ECHOES-X) study

PubMed Central

Taylor, Clare J; Roalfe, Andrea K; Tait, Lynda; Davis, Russell C; Iles, Rachel; Derit, Marites; Hobbs, F D Richard

2014-01-01

Objectives Rescreen a large community cohort to examine the progression to heart failure over time and the role of natriuretic peptide testing in screening. Design Observational longitudinal cohort study. Setting 16 socioeconomically diverse practices in central England. Participants Participants from the original Echocardiographic Heart of England Screening (ECHOES) study were invited to attend for rescreening. Outcome measures Prevalence of heart failure at rescreening overall and for each original ECHOES subgroup. Test performance of N Terminal pro-B-type Natriuretic Peptide (NT-proBNP) levels at different thresholds for screening. Results 1618 of 3408 participants underwent screening which represented 47% of survivors and 26% of the original ECHOES cohort. A total of 176 (11%, 95% CI 9.4% to 12.5%) participants were classified as having heart failure at rescreening; 103 had heart failure with reduced ejection fraction (HFREF) and 73 had heart failure with preserved ejection fraction (HFPEF). Sixty-eight out of 1232 (5.5%, 95% CI 4.3% to 6.9%) participants who were recruited from the general population over the age of 45 and did not have heart failure in the original study, had heart failure on rescreening. An NT-proBNP cut-off of 400 pg/mL had sensitivity for a diagnosis of heart failure of 79.5% (95% CI 72.4% to 85.5%) and specificity of 87% (95% CI 85.1% to 88.8%). Conclusions Rescreening identified new cases of HFREF and HFPEF. Progression to heart failure poses a significant threat over time. The natriuretic peptide cut-off level for ruling out heart failure must be low enough to ensure cases are not missed at screening. PMID:25015472

Pregnancy as a Window to Future Cardiovascular Health: Design and Implementation of the nuMoM2b Heart Health Study

PubMed Central

Haas, David M; Ehrenthal, Deborah B; Koch, Matthew A; Catov, Janet M; Barnes, Shannon E; Facco, Francesca; Parker, Corette B; Mercer, Brian M; Bairey-Merz, C Noel; Silver, Robert M; Wapner, Ronald J; Simhan, Hyagriv N; Hoffman, Matthew K; Grobman, William A; Greenland, Philip; Wing, Deborah A; Saade, George R; Parry, Samuel; Zee, Phyllis C; Reddy, Uma M; Pemberton, Victoria L; Burwen, Dale R

2016-01-01

Abstract The National Institute of Child Health and Human Development's Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study (HHS) was designed to investigate the relationships between adverse pregnancy outcomes and modifiable risk factors for cardiovascular disease. The ongoing nuMoM2b-HHS, which started in 2013, is a prospective follow-up of the nuMoM2b cohort, which included 10,038 women recruited between 2010 and 2013 from 8 centers across the United States who were initially observed over the course of their first pregnancies. In this report, we detail the design and study procedures of the nuMoM2b-HHS. Women in the pregnancy cohort who consented to be contacted for participation in future studies were approached at 6-month intervals to ascertain health information and to maintain ongoing contact. Two to 5 years after completion of the pregnancy documented in the nuMoM2b, women in the nuMoM2b-HHS were invited to an in-person study visit. During this visit, they completed psychosocial and medical history questionnaires and had clinical measurements and biological specimens obtained. A subcohort of participants who had objective assessments of sleep-disordered breathing during pregnancy were asked to repeat this investigation. This unique prospective observational study includes a large, geographically and ethnically diverse cohort, rich depth of phenotypic information about adverse pregnancy outcomes, and clinical data and biospecimens from early in the index pregnancy onward. Data obtained from this cohort will provide mechanistic and clinical insights into how data on a first pregnancy can provide information about the potential development of subsequent risk factors for cardiovascular disease. PMID:26825925

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.

Chrono-nutrition: a review of current evidence from observational studies on global trends in time-of-day of energy intake and its association with obesity.

PubMed

Almoosawi, S; Vingeliene, S; Karagounis, L G; Pot, G K

2016-11-01

The importance of the circadian rhythm in regulating human food intake behaviour and metabolism has long been recognised. However, little is known as to how energy intake is distributed over the day in existing populations, and its potential association with obesity. The present review describes global trends in time-of-day of energy intake in the general population based on data from cross-sectional surveys and longitudinal cohorts. Evidence of the association between time-of-day of energy intake and obesity is also summarised. Overall, there were a limited number of cross-sectional surveys and longitudinal cohorts that provided data on time-of-day of energy intake. In the identified studies, a wide variation in time-of-day of energy intake was observed, with patterns of energy distribution varying greatly by country and geographical area. In relation to obesity, eight cross-sectional surveys and two longitudinal cohorts were identified. The association between time-of-day of energy intake and obesity varied widely, with several studies reporting a positive link between evening energy intake and obesity. In conclusion, the current review summarises global trends in time-of-day of energy intake. The large variations across countries and global regions could have important implications to health, emphasising the need to understand the socio-environmental factors guiding such differences in eating patterns. Evidence of the association between time-of-day of energy intake and BMI also varied. Further larger scale collaborations between various countries and regions are needed to sum data from existing surveys and cohorts, and guide our understanding of the role of chrono-nutrition in health.

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

PubMed

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

2017-10-01

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

Initial digital vasculitis in a large multicenter cohort of childhood-onset systemic lupus erythematosus.

PubMed

Sakamoto, Ana Paula; Silva, Clovis Artur; Silva, Marco Felipe Castro da; Lopes, Anandreia Simões; Russo, Gleice Clemente Souza; Sallum, Adriana Maluf Elias; Kozu, Katia; Bonfá, Eloisa; Saad-Magalhães, Claudia; Pereira, Rosa Maria Rodrigues; Len, Claudio Arnaldo; Terreri, Maria Teresa

To assess clinical digital vasculitis (DV) as an initial manifestation of childhood-onset systemic lupus erythematosus (cSLE) within a large population. Multicenter cross-sectional study including 852 cSLE patients (ACR criteria) followed in ten Pediatric Rheumatology centers in São Paulo State, Brazil. DV was observed in 25/852 (3%) cSLE patients. Periungual hemorrhage was diagnosed in 12 (48%), periungual infarction in 7 (28%), tip finger ulceration in 4 (16%), painful nodules in 1 (4%) and gangrene in 1 (4%). A poor outcome, with digital resorption, occurred in 5 (20%). Comparison of patients with and without DV revealed higher frequency of malar rash (80% vs. 53%, p=0.008), discoid rash (16% vs. 4%, p=0.017), photosensitivity (76% vs. 45%, p=0.002) and other cutaneous vasculitides (80% vs. 19%, p<0.0001), whereas the frequency of overall constitutional features (32% vs. 61%, p=0.003), fever (32% vs. 56%, p=0.020) and hepatomegaly (4% vs. 23%, p=0.026) were lower in these patients. Frequency of female gender, severe multi-organ involvement, autoantibodies profile and low complement were alike in both groups (p>0.05). SLEDAI-2K median, DV descriptor excluded, was significantly lower in patients with DV compared to those without this manifestation [10 (0-28) vs. 14 (0-58), p=0.004]. Visceral vasculitis or death were not observed in this cSLE cohort. The frequency of cyclophosphamide use (0% vs. 18%, p=0.014) was significantly lower in the DV group. Our large multicenter study identified clinical DV as one of the rare initial manifestation of active cSLE associated with a mild multisystemic disease, in spite of digital resorption in some of these patients. Copyright © 2017. Published by Elsevier Editora Ltda.

Rationale, design and objectives of ARegPKD, a European ARPKD registry study.

PubMed

Ebner, Kathrin; Feldkoetter, Markus; Ariceta, Gema; Bergmann, Carsten; Buettner, Reinhard; Doyon, Anke; Duzova, Ali; Goebel, Heike; Haffner, Dieter; Hero, Barbara; Hoppe, Bernd; Illig, Thomas; Jankauskiene, Augustina; Klopp, Norman; König, Jens; Litwin, Mieczyslaw; Mekahli, Djalila; Ranchin, Bruno; Sander, Anja; Testa, Sara; Weber, Lutz Thorsten; Wicher, Dorota; Yuzbasioglu, Ayse; Zerres, Klaus; Dötsch, Jörg; Schaefer, Franz; Liebau, Max Christoph

2015-02-18

Autosomal recessive polycystic kidney disease (ARPKD) is a rare but frequently severe disorder that is typically characterized by cystic kidneys and congenital hepatic fibrosis but displays pronounced phenotypic heterogeneity. ARPKD is among the most important causes for pediatric end stage renal disease and a leading reason for liver-, kidney- or combined liver kidney transplantation in childhood. The underlying pathophysiology, the mechanisms resulting in the observed clinical heterogeneity and the long-term clinical evolution of patients remain poorly understood. Current treatment approaches continue to be largely symptomatic and opinion-based even in most-advanced medical centers. While large clinical trials for the frequent and mostly adult onset autosomal dominant polycystic kidney diseases have recently been conducted, therapeutic initiatives for ARPKD are facing the challenge of small and clinically variable cohorts for which reliable end points are hard to establish. ARegPKD is an international, mostly European, observational study to deeply phenotype ARPKD patients in a pro- and retrospective fashion. This registry study is conducted with the support of the German Society for Pediatric Nephrology (GPN) and the European Study Consortium for Chronic Kidney Disorders Affecting Pediatric Patients (ESCAPE Network). ARegPKD clinically characterizes long-term ARPKD courses by a web-based approach that uses detailed basic data questionnaires in combination with yearly follow-up visits. Clinical data collection is accompanied by associated biobanking and reference histology, thus setting roots for future translational research. The novel registry study ARegPKD aims to characterize miscellaneous subcohorts and to compare the applied treatment options in a large cohort of deeply characterized patients. ARegPKD will thus provide evidence base for clinical treatment decisions and contribute to the pathophysiological understanding of this severe inherited disorder.

Comprehensive Evaluation of Altered Systemic Metabolism and Pancreatic Cancer Risk

DTIC Science & Technology

2016-10-01

To explore altered metabolism is patients with pancreatic cancer, we are conducting studies in participants from four large prospective cohorts, where...participants from four large prospective cohorts, where individuals provide extensive data on metabolic phenotypes, such as obesity and diabetes, and...Pancreatic cancer; Metabolism; Early detection ACCOMPLISHMENTS: What were the major goals of the project? Four major tasks were described

Online Lecture Recordings and Lecture Attendance: Investigating Student Preferences in a Large First Year Psychology Course

ERIC Educational Resources Information Center

Yeung, Alexandra; Raju, Sadhana; Sharma, Manjula D.

2016-01-01

While blended learning has been around for some time, the interplay between lecture recordings, lecture attendance and grades needs further examination particularly for large cohorts of over 1,000 students in 500 seat lecture theatres. This paper reports on such an investigation with a cohort of 1,450 first year psychology students' who indicated…

Symptomatic Dengue in Children in 10 Asian and Latin American Countries.

PubMed

L'Azou, Maïna; Moureau, Annick; Sarti, Elsa; Nealon, Joshua; Zambrano, Betzana; Wartel, T Anh; Villar, Luis; Capeding, Maria R Z; Ochiai, R Leon

2016-03-24

The control groups in two phase 3 trials of dengue vaccine efficacy included two large regional cohorts that were followed up for dengue infection. These cohorts provided a sample for epidemiologic analyses of symptomatic dengue in children across 10 countries in Southeast Asia and Latin America in which dengue is endemic. We monitored acute febrile illness and virologically confirmed dengue (VCD) in 3424 healthy children, 2 to 16 years of age, in Asia (Indonesia, Malaysia, the Philippines, Thailand, and Vietnam) from June 2011 through December 2013 and in 6939 children, 9 to 18 years of age, in Latin America (Brazil, Colombia, Honduras, Mexico, and Puerto Rico) from June 2011 through April 2014. Acute febrile episodes were determined to be VCD by means of a nonstructural protein 1 antigen immunoassay and reverse-transcriptase-polymerase-chain-reaction assays. Dengue hemorrhagic fever was defined according to 1997 World Health Organization criteria. Approximately 10% of the febrile episodes in each cohort were confirmed to be VCD, with 319 VCD episodes (4.6 episodes per 100 person-years) occurring in the Asian cohort and 389 VCD episodes (2.9 episodes per 100 person-years) occurring in the Latin American cohort; no trend according to age group was observed. The incidence of dengue hemorrhagic fever was less than 0.3 episodes per 100 person-years in each cohort. The percentage of VCD episodes requiring hospitalization was 19.1% in the Asian cohort and 11.1% in the Latin American cohort. In comparable age groups (9 to 12 years and 13 to 16 years), the burden of dengue was higher in Asia than in Latin America. The burdens of dengue were substantial in the two regions and in all age groups. Burdens varied widely according to country, but the rates were generally higher and the disease more frequently severe in Asian countries than in Latin American countries. (Funded by Sanofi Pasteur; CYD14 and CYD15 ClinicalTrials.gov numbers, NCT01373281 and NCT01374516.).

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.

Effectiveness, safety and health-related quality of life of multiple sclerosis patients treated with fingolimod: results from a 12-month, real-world, observational PERFORMS study in the Middle East.

PubMed

Achiron, Anat; Aref, Hany; Inshasi, Jihad; Harb, Mohamad; Alroughani, Raed; Bijarnia, Mahendra; Cooke, Kathryn; Yuksel, Ozgur

2017-08-07

Evidence on the use of fingolimod in real-world clinical practice and data on patient-reported health-related quality of life (HRQoL) in countries such as the Middle East are sparse. The Prospective Evaluation of Treatment with Fingolimod for Multiple Sclerosis (PERFORMS) study assessed HRQoL and effectiveness and safety of fingolimod in patients with relapsing-remitting multiples sclerosis (RRMS), primarily in Middle Eastern countries. This 12-month, observational, multicentre, prospective, real-world study was conducted in patients with RRMS who initiated fingolimod or another approved disease-modifying treatment (DMT) within 4 weeks before study entry. Patients were enrolled in a 2:1 ratio to obtain more data in fingolimod and parallel in other DMTs cohort by physicians during routine medical care. Key study outcomes included HRQoL assessed using MS International QoL (MusiQoL), MS relapses and disability. Safety was assessed throughout the study period. Due to the observational nature of the study, no neuroimaging assessments were mandated and central reading was not performed. Of 249 enrolled patients, 247 were included in the analysis (fingolimod cohort 172; other DMTs cohort 75). Overall, the mean age of patients was 36.5 years, 64.4% were women and ~90% were Caucasians. At baseline, mean MS duration since diagnosis was 7.2 years in the fingolimod and 4.8 years in the other DMTs cohorts. Overall, mean changes in MusiQoL index scores were -2.1 in the fingolimod cohort and -0.7 in the other DMTs cohort at Month 12, but improvement was not significant vs. baseline in both cohorts. Proportion of relapse-free patients increased significantly during the study vs. 0-12 months before the study in the fingolimod cohort (80.2% vs. 24.4%; p < 0.0001). Proportion of patients free from disability progression was 86.5% in the fingolimod cohort. The incidences of AEs were 59.9% and 50.6% in the fingolimod and other DMTs cohorts, respectively. First-dose monitoring of fingolimod observed no cases of symptomatic bradyarrhythmia. Three cases of bradycardia were reported in the fingolimod cohort: one after the first dose and two during the study. No cases of macular oedema were observed during the study. Fingolimod treatment maintained QoL over 12 months and was effective in reducing relapse rate and disability progression. No new safety findings were observed in this real-world observational study in Middle Eastern countries.

Analysis of blood-based gene expression in idiopathic Parkinson disease.

PubMed

Shamir, Ron; Klein, Christine; Amar, David; Vollstedt, Eva-Juliane; Bonin, Michael; Usenovic, Marija; Wong, Yvette C; Maver, Ales; Poths, Sven; Safer, Hershel; Corvol, Jean-Christophe; Lesage, Suzanne; Lavi, Ofer; Deuschl, Günther; Kuhlenbaeumer, Gregor; Pawlack, Heike; Ulitsky, Igor; Kasten, Meike; Riess, Olaf; Brice, Alexis; Peterlin, Borut; Krainc, Dimitri

2017-10-17

To examine whether gene expression analysis of a large-scale Parkinson disease (PD) patient cohort produces a robust blood-based PD gene signature compared to previous studies that have used relatively small cohorts (≤220 samples). Whole-blood gene expression profiles were collected from a total of 523 individuals. After preprocessing, the data contained 486 gene profiles (n = 205 PD, n = 233 controls, n = 48 other neurodegenerative diseases) that were partitioned into training, validation, and independent test cohorts to identify and validate a gene signature. Batch-effect reduction and cross-validation were performed to ensure signature reliability. Finally, functional and pathway enrichment analyses were applied to the signature to identify PD-associated gene networks. A gene signature of 100 probes that mapped to 87 genes, corresponding to 64 upregulated and 23 downregulated genes differentiating between patients with idiopathic PD and controls, was identified with the training cohort and successfully replicated in both an independent validation cohort (area under the curve [AUC] = 0.79, p = 7.13E-6) and a subsequent independent test cohort (AUC = 0.74, p = 4.2E-4). Network analysis of the signature revealed gene enrichment in pathways, including metabolism, oxidation, and ubiquitination/proteasomal activity, and misregulation of mitochondria-localized genes, including downregulation of COX4I1 , ATP5A1 , and VDAC3 . We present a large-scale study of PD gene expression profiling. This work identifies a reliable blood-based PD signature and highlights the importance of large-scale patient cohorts in developing potential PD biomarkers. © 2017 American Academy of Neurology.

An Agent-Based Modeling Template for a Cohort of Veterans with Diabetic Retinopathy.

PubMed

Day, Theodore Eugene; Ravi, Nathan; Xian, Hong; Brugh, Ann

2013-01-01

Agent-based models are valuable for examining systems where large numbers of discrete individuals interact with each other, or with some environment. Diabetic Veterans seeking eye care at a Veterans Administration hospital represent one such cohort. The objective of this study was to develop an agent-based template to be used as a model for a patient with diabetic retinopathy (DR). This template may be replicated arbitrarily many times in order to generate a large cohort which is representative of a real-world population, upon which in-silico experimentation may be conducted. Agent-based template development was performed in java-based computer simulation suite AnyLogic Professional 6.6. The model was informed by medical data abstracted from 535 patient records representing a retrospective cohort of current patients of the VA St. Louis Healthcare System Eye clinic. Logistic regression was performed to determine the predictors associated with advancing stages of DR. Predicted probabilities obtained from logistic regression were used to generate the stage of DR in the simulated cohort. The simulated cohort of DR patients exhibited no significant deviation from the test population of real-world patients in proportion of stage of DR, duration of diabetes mellitus (DM), or the other abstracted predictors. Simulated patients after 10 years were significantly more likely to exhibit proliferative DR (P<0.001). Agent-based modeling is an emerging platform, capable of simulating large cohorts of individuals based on manageable data abstraction efforts. The modeling method described may be useful in simulating many different conditions where course of disease is described in categorical stages.

Anti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis.

PubMed

Jendrek, Sebastian Torben; Gotthardt, Daniel; Nitzsche, Thomas; Widmann, Laila; Korf, Tobias; Michaels, Maike Anna; Weiss, Karl-Heinz; Liaskou, Evaggelia; Vesterhus, Mette; Karlsen, Tom Hemming; Mindorf, Swantje; Schemmer, Peter; Bär, Florian; Teegen, Bianca; Schröder, Torsten; Ehlers, Marc; Hammers, Christoph Matthias; Komorowski, Lars; Lehnert, Hendrik; Fellermann, Klaus; Derer, Stefanie; Hov, Johannes Roksund; Sina, Christian

2017-01-01

Pancreatic autoantibodies (PABs), comprising antibodies against glycoprotein 2 (anti-GP2), are typically associated with complicated phenotypes in Crohn's disease, but have also been observed with variable frequencies in patients with UC. In a previous study, we observed a high frequency of primary sclerosing cholangitis (PSC) in patients with anti-GP2-positive UC. We therefore aimed to characterise the role of anti-GP2 in PSC. In an evaluation phase, sera from 138 well-characterised Norwegian patients with PSC were compared with healthy controls (n=52), and patients with UC without PSC (n=62) for the presence of PABs by indirect immunofluorescence. Further, 180 German patients with PSC served as a validation cohort together with 56 cases of cholangiocarcinoma without PSC, 20 of secondary sclerosing cholangitis (SSC) and 18 of autoimmune hepatitis. Anti-GP2 IgA specifically occurred at considerable rates in large bile duct diseases (cholangiocarcinoma=36%, PSC and SSC about 50%). In PSC, anti-GP2 IgA consistently identified patients with poor survival during follow-up (Norwegian/German cohort: p Log Rank=0.016/0.018). Anti-GP2 IgA was associated with the development of cholangiocarcinoma in both PSC cohorts, yielding an overall OR of cholangiocarcinoma in patients with anti-GP2 IgA-positive PSC of 5.0 (p=0.001). Importantly, this association remained independent of disease duration, bilirubin level and age. Anti-GP2 IgA can be hypothesised as a novel marker in large bile duct diseases. In particular, in PSC, anti-GP2 IgA identified a subgroup of patients with severe phenotype and poor survival due to cholangiocarcinoma. Anti-GP2 IgA may therefore be a clinically valuable tool for risk stratification in PSC. 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/.

Pre- and postfortification intake of folate and risk of colorectal cancer in a large prospective cohort study in the United States123

PubMed Central

Gibson, Todd M; Weinstein, Stephanie J; Pfeiffer, Ruth M; Hollenbeck, Albert R; Subar, Amy F; Schatzkin, Arthur; Mayne, Susan T; Stolzenberg-Solomon, Rachael

2011-01-01

Background: A higher folate intake is associated with a decreased colorectal cancer risk in observational studies, but recent evidence suggests that excessive folate supplementation may increase colorectal cancer risk in some individuals. Therefore, mandatory folic acid fortification of grain products in the United States may have unintended negative consequences. Objective: We examined the association between folate intake and colorectal cancer risk, including 8.5 y of postfortification follow-up. Design: We examined the association between folate intake and colorectal cancer in the NIH-AARP Diet and Health Study—a US cohort study of 525,488 individuals aged 50–71 y initiated in 1995–1996. Dietary, supplemental, and total folate intakes were calculated for the pre- and postfortification periods (before and after 1 July 1997) based on a baseline food-frequency questionnaire. HRs and 95% CIs were calculated by using multivariable Cox proportional hazards regression models. Results: During follow-up through 31 December 2006 (mean follow-up: 9.1 y), 7212 incident colorectal cancer cases were identified. In the postfortification analysis (6484 cases), a higher total folate intake was associated with a decreased colorectal cancer risk (HR for ≥900 compared with <200 μg/d: 0.70; 95% CI: 0.58, 0.84). The highest intakes specifically from supplements (HR: 0.82; 95% CI: 0.72, 0.92) or from diet (HR: 0.81; 95% CI: 0.67, 0.97) were also protective. The pattern of associations was similar for the prefortification period, and no significant differences between time periods were observed. Conclusions: In this large prospective cohort study that included 8.5 y of postfortification follow-up, folate intake was associated with a decreased colorectal cancer risk. Given that the adenoma-carcinoma sequence may take ≥10 y, additional follow-up time is needed to fully examine the effect of folic acid fortification. PMID:21813806

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.

Large prospective birth cohort studies on environmental contaminants and child health - goals, challenges, limitations and needs.

PubMed

Luo, Zhong-Cheng; Liu, Jian-Meng; Fraser, William D

2010-02-01

The adverse health effects of environmental contaminants (ECs) are a rising public health concern, and a major threat to sustainable socioeconomic development. The developing fetuses and growing children are particularly vulnerable to the adverse effects of ECs. However, assessing the health impact of ECs presents a major challenge, given that multiple outcomes may arise from one exposure, multiple exposures may result in one outcome, and the complex interactions between ECs, and between ECs, nutrients and genetic factors, and the dynamic temporal changes in EC exposures during the life course. Large-scale prospective birth cohort studies collecting extensive data and specimen starting from the prenatal or pre-conception period, although costly, hold promise as a means to more clearly quantify the health effects of ECs, and to unravel the complex interactions between ECs, nutrients and genotypes. A number of such large-scale studies have been launched in some developed counties. We present an overview of "why", "what" and "how" behind these efforts with an objective to uncover major unidentified limitations and needs. Three major limitations were identified: (1) limited data and bio-specimens regarding early life EC exposure assessments in some birth cohort studies; (2) heavy participant burdens in some birth cohort studies may bias participant recruitment, and risk substantial loss to follow-up, protocol deviations limiting the quality of data and specimens collection, with an overall potential bias towards the null effect; (3) lack of concerted efforts in building comparable birth cohorts across countries to take advantage of natural "experiments" (large EC exposure level differences between countries) for more in-depth assessments of dose-response relationships, threshold exposure levels, and positive and negative effect modifiers. Addressing these concerns in current or future large-scale birth cohort studies may help to produce better evidence on the health effects of ECs.

Association of chronic obstructive pulmonary disease and hemorrhoids: A nationwide cohort study.

PubMed

Lin, Lih-Hwa; Siu, Justin Ji-Yuen; Liao, Po-Chi; Chiang, Jen-Huai; Chou, Pei-Chi; Chen, Huey-Yi; Ho, Tsung-Jung; Tsai, Ming-Yen; Chen, Yung-Hsiang; Chen, Wen-Chi

2017-03-01

According to traditional Chinese medicine (TCM) theory, a specific physiological and pathological relationship exists between the lungs and the large intestine. The aim of this study is to delineate the association of chronic obstructive pulmonary disease (COPD) and hemorrhoids in order to verify the "interior-exterior" relationship between the lungs and the large intestine. A retrospective cohort study is conceived from the National Health Insurance Research Database, Taiwan. The 2 samples (COPD cohort and non-COPD cohort) were selected from the 2000 to 2003 beneficiaries of the NHI, representing patients age 20 and older in Taiwan, with the follow-up ending on December 31, 2011. The COPD cohort (n = 51,506) includes every patient newly diagnosed as having Chronic Obstructive Pulmonary Disease (COPD, ICD-9-CM: 490-492, 494, 496), who have made at least 2 confirmed visits to the hospital/clinic. The non-COPD cohort (n = 103,012) includes patients without COPD and is selected via a 1:2 (COPD: non-COPD) matching by age group (per 5 years), gender, and index date (diagnosis date of COPD for the COPD cohort). Compared with non-COPD cohorts, patients with COPD have a higher likelihood of having hemorrhoids and the age-, gender- and comorbidies-adjusted hazard ratio (HR) for hemorrhoids is 1.56 (95% confidence intervals [CI]:1.50-1.62). The adjusted HR of hemorrhoids for females is 0.79 (95% CI: 0.77-0.83), which is significantly less than that for males. The elderly groups, 40 to 59 years and aged 60 or above, have higher adjusted HRs than younger age groups (20-39 years), 1.19 (95% CI: 1.14-1.26), and 1.18 (95% CI: 1.12-1.24), respectively. Patients with COPD may have a higher likelihood to have hemorrhoids in this retrospective cohort study. This study verifies the fundamental theorem of TCM that there is a definite pathogenic association between the lungs and large intestine.

“Dynamic Range” of Inferred Phenotypic HIV Drug Resistance Values in Clinical Practice

PubMed Central

Swenson, Luke C.; Pollock, Graham; Wynhoven, Brian; Mo, Theresa; Dong, Winnie; Hogg, Robert S.; Montaner, Julio S. G.; Harrigan, P. Richard

2011-01-01

Background ‘Virtual’ or inferred phenotypes (vPhenotypes) are commonly used to assess resistance to antiretroviral agents in patients failing therapy. In this study, we provide a clinical context for understanding vPhenotype values. Methods All HIV-infected persons enrolled in the British Columbia Drug Treatment Program with a baseline plasma viral load (pVL) and follow-up genotypic resistance and pVL results were included up to October 29, 2008 (N = 5,277). Change from baseline pVL was determined as a function of Virco vPhenotype, and the “dynamic range” (defined here by the 10th and 90th percentiles for fold-change in IC50 amongst all patients) was estimated from the distribution of vPhenotye fold-changes across the cohort. Results The distribution of vPhenotypes from a large cohort of HIV patients who have failed therapy are presented for all available antiretroviral agents. A maximum change in IC50 of at least 13-fold was observed for all drugs. The dideoxy drugs, tenofovir and most PIs exhibited small “dynamic ranges” with values of <4-fold change observed in >99% of samples. In contrast, zidovudine, lamivudine, emtricitabine and the non-nucleoside reverse transcriptase inihibitors (excluding etravirine) had large dynamic ranges. Conclusion We describe the populational distribution of vPhenotypes such that vPhenotype results can be interpreted relative to other patients in a drug-specific manner. PMID:21390218

Air pollution exposure and adverse pregnancy outcomes in a large UK birth cohort: use of a novel spatio-temporal modelling technique.

PubMed

Hannam, Kimberly; McNamee, Roseanne; Baker, Philip; Sibley, Colin; Agius, Raymond

2014-09-01

Previous work suggests an association between air pollution exposure and adverse pregnancy outcomes, even at relatively low concentrations. Our aim was to quantify the effect of air pollution having an adverse effect on preterm birth (PTB) and fetal growth in a large UK cohort using a novel exposure estimation technique [spatio-temporal (S-T) model] alongside a traditional nearest stationary monitor technique (NSTAT). All available postcodes from a Northwest England birth outcome dataset during 2004-2008 were geocoded (N=203 562 deliveries). Pollution estimates were linked to corresponding pregnancy periods using temporally adjusted background modelled concentrations as well as NSTAT. Associations with PTB, small for gestational age (SGA), and birth weight were investigated using regression models adjusting for maternal age, ethnicity, parity, birth season, socioeconomic status (SES), body mass index (BMI), and smoking. Based on the novel S-T model, a small statistically significant association was observed for particulate matter (PM10) and SGA, particularly with exposure in the first and third trimesters. Similar effects on SGA were also found for nitrogen dioxide (NO 2), particulate matter (PM 2,5), and carbon monoxide (CO) in later pregnancy, but no overall increased risk was observed. No associations were found with NO xor the outcomes PTB and reduction in birth weight. Our findings suggest an association between air pollution exposure and birth of a SGA infant, particularly in the later stages of pregnancy but not with PTB or mean birth weight change.

Birth Weight and Subsequent Risk of Cancer

PubMed Central

Spracklen, Cassandra N; Wallace, Robert B; Sealy-Jefferson, Shawnita; Robinson, Jennifer G; Freudenheim, Jo L; Wellons, Melissa F; Saftlas, Audrey F; Snetselaar, Linda G; Manson, JoAnn E; Hou, Lifang; Qi, Lihong; Chlebowski, Rowan T; Ryckman, Kelli K

2014-01-01

Background We aimed to determine the association between self-reported birth weight and incident cancer in the Women’s Health Initiative Observational Study cohort, a large multiethnic cohort of postmenopausal women. Methods 65,850 women reported their birth weight by category (<6 lbs., 6 lbs.–7 lbs. 15 oz., 8 lbs.–9 lbs. 15 oz., and ≥10 lbs.). All self-reported, incident cancers were adjudicated by study staff. We used Cox proportional hazards regression to estimate crude and adjusted hazard ratios (aHR) for associations between birth weight and: 1) all cancer sites combined, 2) gynecologic cancers, and 3) several site-specific cancer sites. Results After adjustments, birth weight was positively associated with the risk of lung cancer (p=0.01), and colon cancer (p=0.04). An inverse trend was observed between birth weight and risk for leukemia (p=0.04). A significant trend was not observed with breast cancer risk (p=0.67); however, women born weighing ≥10 lbs. were less likely to develop breast cancer compared to women born between 6 lbs.–7 lbs. 15 oz (aHR 0.77, 95% CI 0.63, 0.94). Conclusion Birth weight category appears to be significantly associated with the risk of any postmenopausal incident cancer, though the direction of the association varies by cancer type. PMID:25096278

Impact of Laparoscopic Repair of Large Hiatus Hernia on Quality of Life: Observational Cohort Study.

PubMed

Siboni, Stefano; Asti, Emanuele; Milito, Pamela; Bonitta, Gianluca; Sironi, Andrea; Aiolfi, Alberto; Bonavina, Luigi

2018-06-20

Laparoscopic surgery has proven safe and effective in the treatment of large hiatus hernia. Differences may exist between objectively assessed surgical outcomes, symptomatic scores, and patient-reported outcomes. An observational, single-arm cohort study was conducted in patients undergoing primary laparoscopic repair with crura mesh augmentation and Toupet fundoplication for large (> 50% of intrathoracic stomach) type III-IV hiatus hernia. Data were extracted from hospital charts and a prospectively updated research database. The main study outcome was quality of life assessed by the Gastroesophageal reflux disease Health-Related Quality of Life (GERD-HRQL) score and the Short-form 36 (SF-36). Between 2013 and 2016, 37 out of 49 operated patients completed the comprehensive quality-of-life evaluation at the 2-year follow-up. The GERD-HRQL score significantly decreased compared to baseline (p < 0.001). All items of the SF-36 significantly improved compared to baseline (p < 0.05). Both Physical and Mental Component Summary scores were significantly higher than preoperative scores, with a medium Cohen's effect size (-0.77 and 0.56, respectively). At the 2-year follow-up, symptoms had disappeared in the majority of patients. The use of proton-pump inhibitors significantly decreased compared to baseline (13.5 vs. 86.4%, p < 0.001). Also, the use of antidepressants and benzodiazepines significantly decreased after surgery (8.1 vs. 32.4%, p < 0.001). The overall alimentary satisfaction score was > 8 in 92% of patients. There were no safety issues related to the use of the absorbable synthetic mesh. The incidence of anatomical hernia recurrence was 5.4%, but no patient with recurrent hernia required surgical revision. Laparoscopic repair of large hiatus hernia with mesh and partial fundoplication is associated with symptomatic relief, no side-effects, and a significant improvement in disease-specific and generic quality of life at 2-year follow-up. © 2018 S. Karger AG, Basel.

Multi-ethnic genome-wide association study identifies novel locus for type 2 diabetes susceptibility

PubMed Central

Cook, James P; Morris, Andrew P

2016-01-01

Genome-wide association studies (GWAS) have traditionally been undertaken in homogeneous populations from the same ancestry group. However, with the increasing availability of GWAS in large-scale multi-ethnic cohorts, we have evaluated a framework for detecting association of genetic variants with complex traits, allowing for population structure, and developed a powerful test of heterogeneity in allelic effects between ancestry groups. We have applied the methodology to identify and characterise loci associated with susceptibility to type 2 diabetes (T2D) using GWAS data from the Resource for Genetic Epidemiology on Adult Health and Aging, a large multi-ethnic population-based cohort, created for investigating the genetic and environmental basis of age-related diseases. We identified a novel locus for T2D susceptibility at genome-wide significance (P<5 × 10−8) that maps to TOMM40-APOE, a region previously implicated in lipid metabolism and Alzheimer's disease. We have also confirmed previous reports that single-nucleotide polymorphisms at the TCF7L2 locus demonstrate the greatest extent of heterogeneity in allelic effects between ethnic groups, with the lowest risk observed in populations of East Asian ancestry. PMID:27189021

Peer Assessment in Large Undergraduate Classes: An Evaluation of a Procedure for Marking Laboratory Reports and a Review of Related Practices

ERIC Educational Resources Information Center

Harris, Judy R.

2011-01-01

This study provides evidence that peer marking can be a reliable tool for assessing laboratory reports in large cohorts. It was conducted over a 4-yr period with first-year undergraduates ([asymptotically equivalent to]180 students/cohort) taking a mammalian physiology course, but the procedure adopted would be applicable to any other…

Stochastic and compensatory effects limit persistence of variation in body mass of young caribou

USGS Publications Warehouse

Dale, Bruce W.; Adams, Layne G.; Collins, William B.; Joly, Kyle; Valkenburg, Patrick; Tobey, Robert

2008-01-01

Nutritional restriction during growth can have short- and long-term effects on fitness; however, animals inhabiting uncertain environments may exhibit adaptations to cope with variation in food availability. We examined changes in body mass in free-ranging female caribou (Rangifer tarandus) by measuring mass at birth and at 4, 11, and 16 months of age to evaluate the relative importance of seasonal nutrition to growth, the persistence of cohort-specific variation in body mass through time, and compensatory growth of individuals. Relative mean body mass of cohorts did not persist through time. Compensatory growth of smaller individuals was not observed in summer; however, small calves exhibited more positive change in body mass than did large calves. Compensation occurred during periods of nutritional restriction (winter) rather than during periods of rapid growth (summer) thus differing from the conventional view of compensatory growth.

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.

A prospective cohort study on the association between coffee drinking and risk of non-gallstone-related acute pancreatitis.

PubMed

Oskarsson, Viktor; Sadr-Azodi, Omid; Orsini, Nicola; Wolk, Alicja

2016-05-28

Only one previous study has examined the association between coffee consumption and risk of acute pancreatitis, and it found a reduced risk for alcohol-related episodes among high consumers of coffee. Therefore, we examined (1) the association between coffee consumption and risk of non-gallstone-related acute pancreatitis and (2) whether this association was modified by alcohol intake. Data were obtained from two prospective cohorts, the Cohort of Swedish Men and the Swedish Mammography Cohort, including 76 731 men and women (born 1914-1952). Coffee consumption was assessed at baseline with a FFQ, and the cohorts were followed up between 1998 and 2012 via linkage to national health registries. Hazard ratios were estimated using Cox models, with adjustment for potential confounding factors. During 1 035 881 person-years of total follow-up, 383 cases (246 in men and 137 in women) of incident non-gallstone-related acute pancreatitis were identified. Overall, and irrespective of whether a categorical or a continuous exposure model was used, we observed no association between coffee consumption and risk of non-gallstone-related acute pancreatitis (e.g. the multivariable-adjusted hazard ratio for each 1 cup/d increase in coffee consumption was 0·97; 95 % CI 0·92, 1·03). There was no evidence of effect modification by alcohol intake (P interaction=0·77). In conclusion, coffee consumption was not associated with risk of non-gallstone-related acute pancreatitis in this large prospective cohort study. Because of the limited number of epidemiological studies and their conflicting results, further research is needed to elucidate this potential association.

Entacapone and prostate cancer in Parkinson's disease patients: A large Veterans Affairs healthcare system study.

PubMed

Major, Jacqueline M; Dong, Diane; Cunningham, Francesca; By, Kunthel; Hur, Kwan; Shih, David C; Jiang, Rong; Podskalny, Gerald D; Wei, XiangMing; Pinheiro, Simone; Bird, Steven T; Keeton, Stephine; Graham, David J

2018-05-05

An increased incidence of prostate cancer was observed in Parkinson's disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial; the relation has not been robustly investigated in the U.S. ambulatory setting. To investigate whether entacapone is associated with prostate cancer and to assess whether the associations are correlated with advanced disease at the time of cancer diagnosis. Using data from the Department of Veterans Affairs healthcare system, new-user cohorts were created of PD patients treated with add-on entacapone or add-on dopamine agonist/monoamine oxidase B inhibitors between January 2000 and December 2014. Patients were followed on-treatment for occurrence of prostate cancer, identified via linkage to the VA cancer registry. Mean follow-up time was 3.1 and 4.0 years in the entacapone and control cohort, respectively. There were 17,666 subjects meeting study criteria (mean age, 74 (SD 8.6) years); the entacapone-treated group comprised 5,257 subjects. Twenty-three prostate cancer cases occurred in the entacapone cohort and ninety-seven in the control cohort. The overall incidence of prostate cancer was 1.8 per 1,000 person-years of risk. There was no difference in risk of prostate cancer between the cohorts for increased duration of entacapone intake (adjusted HR: 1.08; 95% confidence interval: 0.46-2.51 for cumulative exposure of ≥2 years). Time since starting drug therapy and cumulative dose (mg) also do not suggest a difference in prostate cancer risk between cohorts. Prolonged therapy with entacapone was not associated with increased prostate cancer incidence; however, findings suggest a higher severity of prostate cancer. Published by Elsevier Ltd.

Echocardiographic agreement in the diagnostic evaluation for infective endocarditis.

PubMed

Lauridsen, Trine Kiilerich; Selton-Suty, Christine; Tong, Steven; Afonso, Luis; Cecchi, Enrico; Park, Lawrence; Yow, Eric; Barnhart, Huiman X; Paré, Carlos; Samad, Zainab; Levine, Donald; Peterson, Gail; Stancoven, Amy Butler; Johansson, Magnus Carl; Dickerman, Stuart; Tamin, Syahidah; Habib, Gilbert; Douglas, Pamela S; Bruun, Niels Eske; Crowley, Anna Lisa

2016-07-01

Echocardiography is essential for the diagnosis and management of infective endocarditis (IE). However, the reproducibility for the echocardiographic assessment of variables relevant to IE is unknown. Objectives of this study were: (1) To define the reproducibility for IE echocardiographic variables and (2) to describe a methodology for assessing quality in an observational cohort containing site-interpreted data. IE reproducibility was assessed on a subset of echocardiograms from subjects enrolled in the International Collaboration on Endocarditis registry. Specific echocardiographic case report forms were used. Intra-observer agreement was assessed from six site readers on ten randomly selected echocardiograms. Inter-observer agreement between sites and an echocardiography core laboratory was assessed on a separate random sample of 110 echocardiograms. Agreement was determined using intraclass correlation (ICC), coverage probability (CP), and limits of agreement for continuous variables and kappa statistics (κweighted) and CP for categorical variables. Intra-observer agreement for LVEF was excellent [ICC = 0.93 ± 0.1 and all pairwise differences for LVEF (CP) were within 10 %]. For IE categorical echocardiographic variables, intra-observer agreement was best for aortic abscess (κweighted = 1.0, CP = 1.0 for all readers). Highest inter-observer agreement for IE categorical echocardiographic variables was obtained for vegetation location (κweighted = 0.95; 95 % CI 0.92-0.99) and lowest agreement was found for vegetation mobility (κweighted = 0.69; 95 % CI 0.62-0.86). Moderate to excellent intra- and inter-observer agreement is observed for echocardiographic variables in the diagnostic assessment of IE. A pragmatic approach for determining echocardiographic data reproducibility in a large, multicentre, site interpreted observational cohort is feasible.

Earning Differences by Major Field of Study: Evidence from Three Cohorts of Recent Canadian Graduates.

ERIC Educational Resources Information Center

Finnie, Ross; Frenette, Marc

2003-01-01

Analysis of earnings differences by major field of study of three cohorts of graduates (1982, 1986, 1990) with bachelors' degrees from Canadian postsecondary institutions. Finds that earnings differences are large and statistically significant. The patterns are relatively consistent for the three cohorts and for male and female graduates, 2 and 5…

Cohort-Specific Online Discussion Experiences: A Collaborative and Multidisciplinary Approach to Improving Student Learning

ERIC Educational Resources Information Center

Selhorst, Adam L.; Klein, Eric; Harrison, Justin

2017-01-01

Research addressing the effects of cohort size on student success in asynchronous online discussions is sparse. As such, the following study attempted to determine an optimal student cohort size to enhance success and engagement within online discussions in general education courses at a large post-secondary university consisting of predominately…

A comprehensive survey of genetic variation in 20,691 subjects from four large cohorts

PubMed Central

Loomis, Stephanie; Turman, Constance; Huang, Hongyan; Huang, Jinyan; Aschard, Hugues; Chan, Andrew T.; Choi, Hyon; Cornelis, Marilyn; Curhan, Gary; De Vivo, Immaculata; Eliassen, A. Heather; Fuchs, Charles; Gaziano, Michael; Hankinson, Susan E.; Hu, Frank; Jensen, Majken; Kang, Jae H.; Kabrhel, Christopher; Liang, Liming; Pasquale, Louis R.; Rimm, Eric; Stampfer, Meir J.; Tamimi, Rulla M.; Tworoger, Shelley S.; Wiggs, Janey L.; Hunter, David J.; Kraft, Peter

2017-01-01

The Nurses’ Health Study (NHS), Nurses’ Health Study II (NHSII), Health Professionals Follow Up Study (HPFS) and the Physicians Health Study (PHS) have collected detailed longitudinal data on multiple exposures and traits for approximately 310,000 study participants over the last 35 years. Over 160,000 study participants across the cohorts have donated a DNA sample and to date, 20,691 subjects have been genotyped as part of genome-wide association studies (GWAS) of twelve primary outcomes. However, these studies utilized six different GWAS arrays making it difficult to conduct analyses of secondary phenotypes or share controls across studies. To allow for secondary analyses of these data, we have created three new datasets merged by platform family and performed imputation using a common reference panel, the 1,000 Genomes Phase I release. Here, we describe the methodology behind the data merging and imputation and present imputation quality statistics and association results from two GWAS of secondary phenotypes (body mass index (BMI) and venous thromboembolism (VTE)). We observed the strongest BMI association for the FTO SNP rs55872725 (β = 0.45, p = 3.48x10-22), and using a significance level of p = 0.05, we replicated 19 out of 32 known BMI SNPs. For VTE, we observed the strongest association for the rs2040445 SNP (OR = 2.17, 95% CI: 1.79–2.63, p = 2.70x10-15), located downstream of F5 and also observed significant associations for the known ABO and F11 regions. This pooled resource can be used to maximize power in GWAS of phenotypes collected across the cohorts and for studying gene-environment interactions as well as rare phenotypes and genotypes. PMID:28301549

Achieving consensus on minimum data items (including core outcome domains) for a longitudinal observational cohort study in rheumatoid arthritis.

PubMed

Nikiphorou, Elena; Mackie, Sarah L; Kirwan, John; Boers, Martin; Isaacs, John; Morgan, Ann W; Young, Adam

2017-04-01

To obtain consensus on the minimum data items for an observational cohort study in RA in the UK and to make available the process for similar studies and other rheumatic conditions. Individuals with a diverse range of expertise and backgrounds were invited to participate in a process of proposing a minimum core dataset (MCD) for research studies, commissioned by Arthritis Research UK as part of the larger INBANK project. The group included patients and representatives from clinical and academic rheumatology, outcomes science, stratified medicine, health economics, and national professional and academic bodies/committees. A process was devised based on OMERACT principles for reviewing aims/objectives, defining the scope, identifying the important research questions and selecting key domains. Following the initial multistakeholder meeting, subsequent teleconferences and email communications: consensus was obtained on the most important and relevant research questions; agreement on how the OMERACT Core Areas (life impact, pathophysiological manifestations, resource use and death) could form the basis of a MCD; and consensus on 22 items for inclusion into a MCD. Workshops were undertaken for two essential items that required further exploration: work/social participation and co-morbidity. Reaching a consensus for the proposed minimal data items for long-term observational cohort studies of RA in the UK posed novel challenges and opportunities, and was largely successful. Further work is needed for selecting instruments for two important items and for achieving compatibility with other UK national initiatives, and more widely across Europe. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Dramatic decline in substance use by HIV-infected pregnant women in the United States from 1990 to 2012.

PubMed

Rough, Kathryn; Tassiopoulos, Katherine; Kacanek, Deborah; Griner, Raymond; Yogev, Ram; Rich, Kenneth C; Seage, George R

2015-01-02

We aimed to describe temporal changes in substance use among HIV-infected pregnant women in the United States from 1990 to 2012. Data came from two prospective cohort studies (Women and Infants Transmission Study and Surveillance Monitoring for Antiretroviral Therapy Toxicities Study). Women were classified as using a substance during pregnancy if they self-reported use or had a positive biological sample. To account for correlation between repeated pregnancies by the same woman, generalized estimating equation models were used to test for temporal trends and evaluate predictors of substance use. Over the 23-year period, substance use among the 5451 HIV-infected pregnant women sharply declined; 82% of women reported substance use during pregnancy in 1990, compared with 23% in 2012. Use of each substance decreased significantly (P < 0.001 for each substance) in an approximately linear fashion, until reaching a plateau in 2006. Multivariable models showed substance use was inversely associated with receiving antiretroviral therapy. Among the subset of 824 women with multiple pregnancies under observation, women who used a substance in their previous pregnancy were at elevated risk of substance use during their next pregnancy (risk ratio, 5.71; 95% confidence interval, 4.63-7.05). A substantial decrease in substance use during pregnancy was observed between 1990 and 2012 in two large US cohorts of HIV-infected women. Substance use prevalence in these cohorts became similar to that of pregnant women in the general US population by the mid-2000s, suggesting that the observed decrease may be due to an epidemiological transition of the HIV epidemic among women in the United States.

Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study.

PubMed

Gillard, Paul; Yang, Pan-Chyr; Danilovits, Manfred; Su, Wei-Juin; Cheng, Shih-Lung; Pehme, Lea; Bollaerts, Anne; Jongert, Erik; Moris, Philippe; Ofori-Anyinam, Opokua; Demoitié, Marie-Ange; Castro, Marcela

2016-09-01

Previous studies have shown that the M72/AS01E candidate tuberculosis vaccine is immunogenic with a clinically acceptable safety profile in healthy and Mycobacterium tuberculosis-infected adults. This phase II, observer-blind, randomised study compared the safety, reactogenicity, and immunogenicity of M72/AS01E in 3 cohorts: tuberculosis-naïve adults (n = 80), adults previously treated for tuberculosis (n = 49), and adults who have completed the intensive phase of tuberculosis treatment (n = 13). In each cohort, 18-59-year-old adults were randomised (1:1) to receive two doses of M72/AS01E (n = 71) or placebo (n = 71) and followed-up until six months post-dose 2. Safety and reactogenicity were assessed as primary objective. Recruitment in the study ended prematurely because of a high incidence of large injection site redness/swelling reactions in M72/AS01E-vaccinated adults undergoing tuberculosis treatment. No additional clinically relevant adverse events were observed, except one possibly vaccine-related serious adverse event (hypersensitivity in a tuberculosis-treated-M72/AS01E participant). Robust and persistent M72-specific humoral and polyfunctional CD4(+) T-cell-mediated immune responses were observed post-M72/AS01E vaccination in each cohort. In conclusion, the M72/AS01E vaccine was immunogenic in adults previously or currently treated for tuberculosis, but further analyses are needed to explain the high local reactogenicity in adults undergoing tuberculosis treatment. ClinicalTrials.gov: NCT01424501. Copyright © 2016 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. 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.

Cardiovascular Disease Risk in NASA Astronauts Across the Lifespan: Historical Cohort Studies

NASA Technical Reports Server (NTRS)

Charvat, Jacqueline M.; Lee, Stuart M. C.; Davenport, Eddie; Barlow, Carolyn E.; Radford, Nina B.; De Fina, Laura F.; Stenger, Michael B.; Van Baalen, Mary

2017-01-01

Acute effects of spaceflight on the cardiovascular system have been studied extensively, but the combined chronic effects of spaceflight and aging are not well understood. Preparation for and participation in space flight activities are potentially associated with cardiovascular disease risk factors (e.g., altered dietary and exercise habits, physical and emotional stress, circadian shifts, radiation). Further, astronauts who travel into space multiple times may be at an increased risk across their lifespan. However, comparing the risk of cardiovascular disease in astronauts to other large cohorts is difficult. For example, comparisons between astronauts and large national cohorts, such as the National Health and Nutrition Examination Survey and the National Health Information Survey, are hampered by significant differences in health status between astronauts and the general population, and most of these national studies fail to provide longitudinal data on population health. To address those limitations, NASA's Longitudinal Study of Astronaut Health previously sought to compare the astronauts to a cohort of civil servants employed at the Johnson Space Center. However, differences between the astronauts and civil servants at the beginning of the study, as well as differential follow up, limited the ability to interpret the results. To resolve some of these limitations, two unique cohorts of healthy workers, U.S. Air Force aviators and Cooper Center Longitudinal Study participants, have been identified as potential comparison populations for the astronaut corps. The Air Force cohort was chosen due to similarities in health at selection, screening, and some occupational exposures that Air Force aviators endure, many of which mirror that of the astronaut corps. The Cooper Clinic cohort, a generally healthy prevention cohort, was chosen for the vast array of clinical cardiovascular measures collected in a longitudinal manner complementary to those collected on astronauts, for a large number of subjects since 1971. The purpose of this study is to understand the incidence of cardiovascular disease outcomes and risk factors in the astronaut corps and determine whether the rates of disease are different than these two cohorts. The research questions are: 1. Are there differences in the incidence of CVD outcomes (MI, revascularization, and stroke) between each cohort and the NASA Astronaut cohort? 2. Are there differences in the incidence of CVD risks (hypertension, hyperlipidemia, arrhythmias, and diabetes) between each cohort and the NASA Astronaut cohort? 3. Are there differences between each cohort and the NASA Astronaut cohort in how CVD risk factors (e.g., lipids, behaviors) change across time? Collectively, results from these studies will enhance our understanding of how cardiovascular disease outcomes and risk factors change across time in astronauts compared to other longitudinally-studied healthy cohorts and determine if there are interactions between or additive effects of the occupational health effects of spaceflight exposure and normal aging.

Mobile phone use and the risk of skin cancer: a nationwide cohort study in Denmark.

PubMed

Poulsen, Aslak Harbo; Friis, Søren; Johansen, Christoffer; Jensen, Allan; Frei, Patrizia; Kjaear, Susanne Krüger; Dalton, Susanne Oksbjerg; Schüz, Joachim

2013-07-15

The International Agency for Research on Cancer has classified radiofrequency radiation as possibly carcinogenic. Previous studies have focused on intracranial tumors, although the skin receives much radiation. In a nationwide cohort study, 355,701 private mobile phone subscribers in Denmark from 1987 to 1995 were followed up through 2007. We calculated incidence rate ratios (IRRs) for melanoma, basal cell carcinoma, and squamous cell carcinoma by using Poisson regression models adjusted for age, calendar period, educational level, and income. Separate IRRs for head/neck tumors and torso/leg tumors were compared (IRR ratios) to further address potential confounders. We observed no overall increased risk for basal cell carcinoma, squamous cell carcinoma, or melanoma of the head and neck. After a follow-up period of at least 13 years, the IRRs for basal cell carcinoma and squamous cell carcinoma remained near unity. Among men, the IRR for melanoma of the head and neck was 1.20 (95% confidence interval: 0.65, 2.22) after a minimum 13-year follow-up, whereas the corresponding IRR for the torso and legs was 1.16 (95% confidence interval: 0.91, 1.47), yielding an IRR ratio of 1.04 (95% confidence interval: 0.54, 2.00). A similar risk pattern was seen among women, though it was based on smaller numbers. In this large, population-based cohort study, little evidence of an increased skin cancer risk was observed among mobile phone users.

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.

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.

Efficient Replication of over 180 Genetic Associations with Self-Reported Medical Data

PubMed Central

Tung, Joyce Y.; Do, Chuong B.; Hinds, David A.; Kiefer, Amy K.; Macpherson, J. Michael; Chowdry, Arnab B.; Francke, Uta; Naughton, Brian T.; Mountain, Joanna L.; Wojcicki, Anne; Eriksson, Nicholas

2011-01-01

While the cost and speed of generating genomic data have come down dramatically in recent years, the slow pace of collecting medical data for large cohorts continues to hamper genetic research. Here we evaluate a novel online framework for obtaining large amounts of medical information from a recontactable cohort by assessing our ability to replicate genetic associations using these data. Using web-based questionnaires, we gathered self-reported data on 50 medical phenotypes from a generally unselected cohort of over 20,000 genotyped individuals. Of a list of genetic associations curated by NHGRI, we successfully replicated about 75% of the associations that we expected to (based on the number of cases in our cohort and reported odds ratios, and excluding a set of associations with contradictory published evidence). Altogether we replicated over 180 previously reported associations, including many for type 2 diabetes, prostate cancer, cholesterol levels, and multiple sclerosis. We found significant variation across categories of conditions in the percentage of expected associations that we were able to replicate, which may reflect systematic inflation of the effects in some initial reports, or differences across diseases in the likelihood of misdiagnosis or misreport. We also demonstrated that we could improve replication success by taking advantage of our recontactable cohort, offering more in-depth questions to refine self-reported diagnoses. Our data suggest that online collection of self-reported data from a recontactable cohort may be a viable method for both broad and deep phenotyping in large populations. PMID:21858135

Treatment choices and neuropsychological symptoms of a large cohort of early MS

PubMed Central

von Bismarck, Olga; Dankowski, Theresa; Ambrosius, Björn; Hessler, Nicole; Antony, Gisela; Ziegler, Andreas; Hoshi, Muna-Miriam; Aly, Lilian; Luessi, Felix; Groppa, Sergiu; Klotz, Luisa; Meuth, Sven G.; Tackenberg, Björn; Stoppe, Muriel; Then Bergh, Florian; Tumani, Hayrettin; Kümpfel, Tania; Stangel, Martin; Heesen, Christoph; Wildemann, Brigitte; Paul, Friedemann; Bayas, Antonios; Warnke, Clemens; Weber, Frank; Linker, Ralf A.; Ziemann, Ulf; Zettl, Uwe K.; Zipp, Frauke; Wiendl, Heinz; Hemmer, Bernhard; Gold, Ralf

2018-01-01

Objective To assess clinical characteristics, distribution of disease-modifying treatments (DMTs), and neuropsychological symptoms in a large cohort of patients with early-stage MS. Methods The German National MS Cohort is a multicenter prospective longitudinal cohort study that has recruited DMT-naive patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RRMS) since 2010. We evaluated their baseline characteristics and the prevalence of neuropsychological symptoms. Results Of 1,124 patients, with a 2.2:1 female-to-male ratio and median age at onset of 31.71 years (interquartile range [IQR]: 26.06–40.33), 44.6% and 55.3% had CIS and RRMS, respectively. The median Expanded Disability Status Scale (EDSS) score at baseline was 1.5 (IQR: 1.0–2.0). A proportion of 67.8% of patients started DMT after a median time of 167.0 days (IQR 90.0–377.5) since the first manifestation. A total of 64.7% and 70.4% of the 762 patients receiving early DMT were classified as CIS and RRMS, respectively. Fatigue, depressive symptoms, and cognitive dysfunction were detected in 36.5%, 33.5%, and 14.7% of patients, respectively. Conclusion Baseline characteristics of this large cohort of patients with early, untreated MS corroborated with other cohorts. Most patients received early DMT within the first year after disease onset, irrespective of a CIS or RRMS diagnosis. Despite the low EDSS score, neuropsychological symptoms affected a relevant proportion of patients. PMID:29511705

Efficient replication of over 180 genetic associations with self-reported medical data.

PubMed

Tung, Joyce Y; Do, Chuong B; Hinds, David A; Kiefer, Amy K; Macpherson, J Michael; Chowdry, Arnab B; Francke, Uta; Naughton, Brian T; Mountain, Joanna L; Wojcicki, Anne; Eriksson, Nicholas

2011-01-01

While the cost and speed of generating genomic data have come down dramatically in recent years, the slow pace of collecting medical data for large cohorts continues to hamper genetic research. Here we evaluate a novel online framework for obtaining large amounts of medical information from a recontactable cohort by assessing our ability to replicate genetic associations using these data. Using web-based questionnaires, we gathered self-reported data on 50 medical phenotypes from a generally unselected cohort of over 20,000 genotyped individuals. Of a list of genetic associations curated by NHGRI, we successfully replicated about 75% of the associations that we expected to (based on the number of cases in our cohort and reported odds ratios, and excluding a set of associations with contradictory published evidence). Altogether we replicated over 180 previously reported associations, including many for type 2 diabetes, prostate cancer, cholesterol levels, and multiple sclerosis. We found significant variation across categories of conditions in the percentage of expected associations that we were able to replicate, which may reflect systematic inflation of the effects in some initial reports, or differences across diseases in the likelihood of misdiagnosis or misreport. We also demonstrated that we could improve replication success by taking advantage of our recontactable cohort, offering more in-depth questions to refine self-reported diagnoses. Our data suggest that online collection of self-reported data from a recontactable cohort may be a viable method for both broad and deep phenotyping in large populations.

Maternal pre-pregnancy body mass index and circulating microRNAs in pregnancy.

PubMed

Enquobahrie, Daniel A; Wander, Pandora L; Tadesse, Mahlet G; Qiu, Chunfang; Holzman, Claudia; Williams, Michelle A

Maternal pre-pregnancy overweight and obese status has been associated with a number of pregnancy complications and adverse offspring outcomes. Mechanisms for observed associations, however, are largely unknown. We investigated associations of pre-pregnancy body mass index with early-mid pregnancy epigenetic biomarkers, circulating microRNAs. Peripheral blood was collected from participants (16-27 weeks gestation) of two multi-racial pregnancy cohorts, the Omega Study and the Pregnancy Outcomes and Community Health Study. Plasma miRNA expression was characterised using epigenome-wide (319 miRNAs) profiling among 20 pregnant women in each cohort. Cohort-specific linear regression models that included the predictor (pre-pregnancy body mass index), the outcome (microRNA expression), and adjustment factors (maternal age, gestational age at blood collection, and race) were fit. Expression of 27 miRNAs was positively associated with pre-pregnancy body mass index in both cohorts (p-values <0.05). A number of these differentially expressed miRNAs have previously been associated with adipogenesis (e.g. let-7d*, miR-103-2*, -130b, -146b-5-p, -29c, and -26b). Identified miRNAs as well as their experimentally validated targets participate in pathways that involve organismal injury, reproductive system disease, connective tissue disorders, cancer, cellular development, growth and proliferation. Pre-pregnancy body mass index is associated with circulating miRNAs in early-mid pregnancy. Published by Elsevier Ltd.

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

PubMed

Taylor, Nathan G A

2017-07-01

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

A Confirmatory Approach to Examining the Factor Structure of the Strengths and Difficulties Questionnaire (SDQ): A Large Scale Cohort Study

ERIC Educational Resources Information Center

Niclasen, Janni; Skovgaard, Anne Mette; Andersen, Anne-Marie Nybo; Somhovd, Mikael Julius; Obel, Carsten

2013-01-01

The aim of this study was to examine the factor structure of the Strengths and Difficulties Questionnaire (SDQ) using a Structural Confirmatory Factor Analytic approach. The Danish translation of the SDQ was distributed to 71,840 parents and teachers of 5-7 and 10-12-year-old boys and girls from four large scale cohorts. Three theoretical models…

Non-typhi Salmonella infection in patients with rheumatic diseases on TNF-alpha antagonist therapy.

PubMed

Peña-Sagredo, J L; Fariñas, M C; Perez-Zafrilla, B; Cruz-Valenciano, A; Crespo, M; Joven-Ibañez, B; Riera, E; Manero-Ruiz, F J; Chalmeta, I; Hernández, M V; Rodríguez-Gómez, M; Maíz, O; López, R; Cobo, T; Pita, J; Carmona, L; Gonzalez-Gay, M A

2009-01-01

The morbidity and mortality of patients with rheumatic diseases has improved considerably following the use of biologic therapies. However, an increase in the frequency of bacterial infections has been observed in patients receiving these drugs. In the present study we aimed to establish the incidence and clinical manifestations of non-typhi Salmonella infection in a large cohort of patients with rheumatic diseases undergoing TNF-alpha antagonist therapy due to severe rheumatic diseases refractory to conventional therapies. The rate of non-typhi Salmonella infection found in the Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases (BIOBADASER) was compared with that observed in a cohort of rheumatoid arthritis (RA) patients from the EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) Study, who were not treated with TNF-alpha antagonists. The rate found in the BIOBADASER registry was also compared with that available in a non-RA historic control cohort reported in a population from Huesca (Northern Spain). Seventeen cases of non-typhi Salmonella infection were observed in the series of patients exposed to anti-TNF-alpha therapies. The incidence rate of non-typhi Salmonella in BIOBADASER was 0.73 per 1000 patient-years (95% confidence interval [CI]: 0.45-1.17). The incidence rate in the EMECAR cohort was 0.44 per 1000 patient-years. The relative risk for non-typhi salmonellosis in RA patients exposed to TNF-alpha inhibitors compared to those not treated with biological therapies was 2.07 (95% CI: 0.27-15.73) (p=0.480) whereas the relative risk of non-typhi Salmonella infections in patients with rheumatic diseases undergoing TNF-alpha antagonist therapy compared with the non-RA Spanish control cohort was 0.63 (95% CI: 0.38-1.04) (p=0.07). Nine of the 17 patients with non-typhi salmonellosis presented a severe systemic infection. Incidence of non-typhi Salmonella infection is not increased significantly in rheumatic patients undergoing anti-TNF-alpha therapy when compared with RA patients undergoing conventional DMARD therapy or with the general population. Nevertheless, at least 50% of patients on TNF-alpha have severe complications once they develop non-typhi Salmonella infection. This fact suggests that anti-TNF-alpha therapies may predispose to salmonella dissemination rather than to infection.

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.

Period Effects, Cohort Effects, and the Narrowing Gender Wage Gap

PubMed Central

Campbell, Colin; Pearlman, Jessica

2015-01-01

Despite the abundance of sociological research on the gender wage gap, questions remain. In particular, the role of cohorts is under investigated. Using data from the Current Population Survey, we use Age-Period-Cohort analysis to uniquely estimate age, period, and cohort effects on the gender wage gap. The narrowing of the gender wage gap that occurred between 1975 and 2009 is largely due to cohort effects. Since the mid-1990s, the gender wage gap has continued to close absent of period effects. While gains in female wages contributed to declines in the gender wage gap for cohorts born before 1950, for later cohorts the narrowing of the gender wage gap is primarily a result of declines in male wages. PMID:24090861

Evaluating performance of risk identification methods through a large-scale simulation of observational data.

PubMed

Ryan, Patrick B; Schuemie, Martijn J

2013-10-01

There has been only limited evaluation of statistical methods for identifying safety risks of drug exposure in observational healthcare data. Simulations can support empirical evaluation, but have not been shown to adequately model the real-world phenomena that challenge observational analyses. To design and evaluate a probabilistic framework (OSIM2) for generating simulated observational healthcare data, and to use this data for evaluating the performance of methods in identifying associations between drug exposure and health outcomes of interest. Seven observational designs, including case-control, cohort, self-controlled case series, and self-controlled cohort design were applied to 399 drug-outcome scenarios in 6 simulated datasets with no effect and injected relative risks of 1.25, 1.5, 2, 4, and 10, respectively. Longitudinal data for 10 million simulated patients were generated using a model derived from an administrative claims database, with associated demographics, periods of drug exposure derived from pharmacy dispensings, and medical conditions derived from diagnoses on medical claims. Simulation validation was performed through descriptive comparison with real source data. Method performance was evaluated using Area Under ROC Curve (AUC), bias, and mean squared error. OSIM2 replicates prevalence and types of confounding observed in real claims data. When simulated data are injected with relative risks (RR) ≥ 2, all designs have good predictive accuracy (AUC > 0.90), but when RR < 2, no methods achieve 100 % predictions. Each method exhibits a different bias profile, which changes with the effect size. OSIM2 can support methodological research. Results from simulation suggest method operating characteristics are far from nominal properties.

Association of Serum Level of Vitamin D at Diagnosis With Breast Cancer Survival: A Case-Cohort Analysis in the Pathways Study.

PubMed

Yao, Song; Kwan, Marilyn L; Ergas, Isaac J; Roh, Janise M; Cheng, Ting-Yuan David; Hong, Chi-Chen; McCann, Susan E; Tang, Li; Davis, Warren; Liu, Song; Quesenberry, Charles P; Lee, Marion M; Ambrosone, Christine B; Kushi, Lawrence H

2017-03-01

There are long-standing interests in the potential benefits of vitamin D for preventing breast cancer recurrence and mortality, yet data from prospective cohort studies are limited. To investigate a serum biomarker of vitamin D status, 25-hydroxyvitamin D (25OHD) measured at the time of breast cancer diagnosis, to determine the association with prognosis. The Pathways Study is a prospective cohort study of breast cancer survivors established in 2006. Enrollment was completed in 2013; follow-up is ongoing. The cohort was established in Kaiser Permanente Northern California, a large integrated health care delivery system in northern California. Women with a diagnosis of incident invasive breast cancer were typically consented and enrolled within 2 months of diagnosis. The overall enrollment rate was 46% (4505 of 9820). Participants are followed for health outcomes and comorbidities at 12, 24, 48, 72, and 96 months after baseline interview. A case-cohort design was used for efficiency assay of 25OHD, selecting 1666 cohort members with serum samples and ensuring representation in the subcohort of races and clinical subtypes. The data analysis was performed from January 5, 2014, to March 15, 2015. Primary outcomes are breast cancer recurrence, second primary cancer, and death. Mean (SD) age was 58.7 (12.4) years. Serum 25OHD concentrations were lower in women with advanced-stage tumors, and the lowest in premenopausal women with triple-negative cancer. Levels were also inversely associated with hazards of disease progression and death. Compared with the lowest tertile, women with the highest tertile of 25OHD levels had superior overall survival (OS). This association remained after adjustment for clinical prognostic factors (hazard ratio [HR], 0.72; 95% CI, 0.54-0.98). Among premenopausal women, the association with OS was stronger, and there were also associations with breast cancer-specific survival and invasive disease-free survival (OS: HR, 0.45; 95% CI, 0.21-0.96; breast cancer-specific survival: HR, 0.37; 95% CI, 0.15-0.93; invasive disease-free survival: HR, 0.58; 95% CI, 0.34-1.01; all after full adjustment). Serum 25OHD levels were independently associated with breast cancer prognostic characteristics and patient prognosis, most prominently among premenopausal women. Our findings from a large, well-characterized prospective cohort provide compelling observational evidence on associations of vitamin D with lower risk of breast cancer morbidity and mortality.

Trends in Dietary Supplement Use in a Cohort of Postmenopausal Women From Iowa

PubMed Central

Park, Kyong; Jacobs, David R.

2009-01-01

Although it is widely known that use of dietary supplements is common in the United States, little is known about use patterns among older Americans. The authors examined trends in dietary supplement use and its contribution to total nutrient intake in the Iowa Women's Health Study cohort in 1986 (baseline) and 2004 (follow-up). The proportion of women who reported using dietary supplements increased substantially between baseline (66%) and follow-up (85%). Moreover, a substantial proportion of women reported using multiple dietary supplements, with 27% using 4 or more products in 2004. Dietary supplements contributed substantially to total intake of many nutrients at baseline, and their contribution became relatively greater at follow-up for most nutrients examined. For most nutrients, no decline in intake was observed, as might have been expected in an aging cohort. Rather, intake of many nutrients increased, primarily because of the rising use of dietary supplements. Use of dietary supplements by older individuals is of particular importance because of the potential benefits of maintaining nutrient intake levels despite potentially declining food intake. However, possible risks from obtaining a large proportion of purified nutrients from dietary supplements rather than deriving them from foods should be studied. PMID:19208725

Lack of association of two chromosome 10q24 SNPs with Alzheimer’s disease

PubMed Central

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

2006-01-01

Several groups have reported evidence of linkage on chromosome 10 to late-onset Alzheimer’s disease (LOAD). In a recent scan of single nucleotide polymorphisms (SNPs) on chromosome 10, significant associations between the rs498055 and rs4417206 SNPs and risk of LOAD were observed. We examined the association of these two SNPs with LOAD risk in a large Caucasian American cohort comprising about 2,000 cases and controls. Neither SNP revealed significant association with LOAD risk or age-at-onset. PMID:17000046

[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.

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.

Merging Models and Biomonitoring Data to Characterize Sources andPathways of Human Exposure to Organophosphorous Pesticides in the SalinasValley of California

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

McKone, Thomas E.; Castorina, Rosemary; Kuwabara, Yu

2006-06-01

By drawing on human biomonitoring data and limited environmental samples together with outputs from the CalTOX multimedia, multipathway source-to-dose model, we characterize cumulative intake of organophosphorous (OP) pesticides in an agricultural region of California. We assemble regional OP pesticide use, environmental sampling, and biological tissue monitoring data for a large and geographically dispersed population cohort of 592 pregnant Latina women in California (the CHAMACOS cohort). We then use CalTOX with regional pesticide usage data to estimate the magnitude and uncertainty of exposure and intake from local sources. We combine model estimates of intake from local sources with food intake basedmore » on national residue data to estimate for the CHAMACOS cohort cumulative median OP intake, which corresponds to expected levels of urinary dialkylphosphate (DAP) metabolite excretion for this cohort. From these results we develop premises about relative contributions from different sources and pathways of exposure. We evaluate these premises by comparing the magnitude and variation of DAPs in the CHAMACOS cohort with the whole U.S. population using data from the National Health and Nutrition Evaluation Survey (NHANES). This comparison supports the premise that in both populations diet is the common and dominant exposure pathway. Both the model results and biomarker comparison supports the observation that the CHAMACOS population has a statistically significant higher intake of OP pesticides that appears as an almost constant additional dose among all participants. We attribute the magnitude and small variance of this intake to non-dietary exposure in residences from local sources.« less

Working Life and Retirement Expectancies at Age 50 by Social Class: Period and Cohort Trends and Projections for Finland.

PubMed

Leinonen, Taina; Martikainen, Pekka; Myrskylä, Mikko

2018-01-11

The balance between the amount of time spent in work and in retirement underlies the long-term sustainability of the social security system. We examined socioeconomic differences in how increasing longevity is distributed between labor market statuses in Finland. We used register data and the Sullivan method to analyze life expectancy at age 50 spent in different labor market statuses over the period 1989-2012 and across cohorts born in 1938-1953. We projected the future mortality and labor market participation rates of partially observed cohorts. Both working life expectancy at age 50 and the share of remaining life spent in work have increased across periods following the recession of the early 1990s, and across successive cohorts. The trends were similar across the social classes, but there were large differences in the numbers of years spent in various states: for the most recent period and the youngest cohort, we find that compared with upper non-manual employees, male and female manual workers were expected to spend 3.6-3.7 fewer years in work, 1.7-4.7 fewer years in statutory retirement, and 3.2-3.9 more years in other forms of nonemployment. Our finding that the share of remaining life at age 50 spent in work is increasing implies that pressure on the welfare system is not as severe as is commonly thought. © The Author(s) 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

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.

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

ERIC Educational Resources Information Center

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

2010-01-01

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

Case-Cohort Studies: Design and Applicability to Hand Surgery.

PubMed

Vojvodic, Miliana; Shafarenko, Mark; McCabe, Steven J

2018-04-24

Observational studies are common research strategies in hand surgery. The case-cohort design offers an efficient and resource-friendly method for risk assessment and outcomes analysis. Case-cohorts remain underrepresented in upper extremity research despite several practical and economic advantages over case-control studies. This report outlines the purpose, utility, and structure of the case-cohort design and offers a sample research question to demonstrate its value to risk estimation for adverse surgical outcomes. The application of well-designed case-cohort studies is advocated in an effort to improve the quality and quantity of observational research evidence in hand and upper extremity surgery. Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

[Application of cohort study in cancer prevention and control].

PubMed

Dai, Min; Bai, Yana; Pu, Hongquan; Cheng, Ning; Li, Haiyan; He, Jie

2016-03-01

Cancer control is a long-term work. Cancer research and intervention really need the support of cohort study. In the recent years, more and more cohort studies on cancer control were conducted in China along with the increased ability of scientific research in China. Since 2010, Cancer Hospital, Chinese Academy of Medical Sciences, collaborated with Lanzhou University and the Worker' s Hospital of Jinchuan Group Company Limited, have carried out a large-scale cohort study on cancer, which covered a population of more than 50 000 called " Jinchang cohort". Since 2012, a National Key Public Health Project, "cancer screening in urban China" , has been conducted in Jinchang, which strengthened the Jinchang cohort study. Based on the Jinchang cohort study, historical cohort study, cross-sectional study and prospective cohort study have been conducted, which would provide a lot of evidence for the cancer control in China.

Within-Cohort Age-Related Differences in Cognitive Functioning

PubMed Central

Salthouse, Timothy A.

2013-01-01

It is widely accepted that the level of cognitive functioning can be influenced by characteristics of the environment that change over time. Many developmental researchers have referred to these influences as cohort effects, and have used year of birth as the basis for determining cohort membership. Furthermore, age-related differences in cognitive functioning are sometimes assumed to be primarily attributable to cohort differences, which implies that differences between birth cohorts should be much larger than differences within birth cohorts. Comparisons of composite scores for five cognitive abilities in different people tested at different ages in different years revealed that within-cohort differences across ages were often as large as between-cohort differences across ages. These results lead to questions about the practice of relying on birth cohort to represent influences on cognitive functioning associated with temporal shifts in characteristics of the environment. PMID:23319401

Risk of cancer among women with polycystic ovary syndrome: a Danish cohort study.

PubMed

Gottschau, Mathilde; Kjaer, Susanne Krüger; Jensen, Allan; Munk, Christian; Mellemkjaer, Lene

2015-01-01

To assess the association between polycystic ovary syndrome (PCOS) and cancer, especially of the endometrium, breast and ovary. The Danish National Patient Register was used to identify 12,070 in- and outpatients in whom PCOS was diagnosed when they were aged 9-49 years during 1977-2012. Using the Danish Cancer Registry, we followed the cohort through 2012 and compared the women's cancer incidence with that of the general Danish female population by means of standardized incidence ratios (SIRs). Cancer was diagnosed in 279 women with PCOS (SIR = 1.19; 95% CI = 1.06-1.34). We found an almost fourfold increased risk for endometrial cancer (numbers observed (N) = 16, SIR = 3.9; 95% CI = 2.2-6.3), the large majority of cases being type 1 (N = 14, SIR = 4.7; 95% CI = 2.6-7.9). We found no association between PCOS and breast (N = 59, SIR = 1.1; 95% CI = 0.8-1.4) or ovarian cancer (N = 10, SIR = 1.8; 95% CI = 0.8-3.2); however, significantly increased risks were found for kidney, colon and brain cancers. The results of this large cohort study support those of case-control studies showing that women with PCOS are at increased risk for endometrial cancer, whereas their risks for breast and ovarian cancer are similar to those of women in the general population. Our finding that women with PCOS also are at increased risk for cancers of the kidney, colon and brain requires further study. Copyright © 2014 Elsevier Inc. All rights reserved.

Optimal convection volume for improving patient outcomes in an international incident dialysis cohort treated with online hemodiafiltration

PubMed Central

Canaud, Bernard; Barbieri, Carlo; Marcelli, Daniele; Bellocchio, Francesco; Bowry, Sudhir; Mari, Flavio; Amato, Claudia; Gatti, Emanuele

2015-01-01

Online hemodiafiltration (OL-HDF), the most efficient renal replacement therapy, enables enhanced removal of small and large uremic toxins by combining diffusive and convective solute transport. Randomized controlled trials on prevalent chronic kidney disease (CKD) patients showed improved patient survival with high-volume OL-HDF, underlining the effect of convection volume (CV). This retrospective international study was conducted in a large cohort of incident CKD patients to determine the CV threshold and range associated with survival advantage. Data were extracted from a cohort of adult CKD patients treated by post-dilution OL-HDF over a 101-month period. In total, 2293 patients with a minimum of 2 years of follow-up were analyzed using advanced statistical tools, including cubic spline analyses for determination of the CV range over which a survival increase was observed. The relative survival rate of OL-HDF patients, adjusted for age, gender, comorbidities, vascular access, albumin, C-reactive protein, and dialysis dose, was found to increase at about 55 l/week of CV and to stay increased up to about 75 l/week. Similar analysis of pre-dialysis β2-microglobin (marker of middle-molecule uremic toxins) concentrations found a nearly linear decrease in marker concentration as CV increased from 40 to 75 l/week. Analysis of log C-reactive protein levels showed a decrease over the same CV range. Thus, a convection dose target based on convection volume should be considered and needs to be confirmed by prospective trials as a new determinant of dialysis adequacy. PMID:25945407

[Epidemiologic profile of juvenile-onset compared to adult-onset spondyloarthritis in a large Brazilian cohort].

PubMed

Duarte, Angela P; Marques, Cláudia D L; Bortoluzzo, Adriana B; Gonçalves, Célio R; da Silva, José Antonio Braga; Ximenes, Antonio Carlos; Bértolo, Manoel B; Ribeiro, Sandra Lúcia E; Keiserman, Mauro; Skare, Thelma L; Carneiro, Sueli; Menin, Rita; Azevedo, Valderilio F; Vieira, Walber P; Albuquerque, Elisa N; Bianchi, Washington A; Bonfiglioli, Rubens; Campanholo, Cristiano; Carvalho, Hellen M S; Costa, Izaias P; Kohem, Charles L; Leite, Nocy; Lima, Sonia A L; Meirelles, Eduardo S; Pereira, Ivânio A; Pinheiro, Marcelo M; Polito, Elizandra; Resende, Gustavo G; Rocha, Francisco Airton C; Santiago, Mittermayer B; Sauma, Maria de Fátima L C; Valim, Valéria; Sampaio-Barros, Percival D; Barros, Percival D Sampaio

2014-01-01

To analyze the clinical and epidemiologic characteristics of juvenile-onset spondyloarthritis (SpA) (< 16 years) and compare them with a group of adult-onset (≥ 16 years) SpA patients. Prospective, observational and multicentric cohort with 1,424 patients with the diagnosis of SpA according to the European Spondyloarthropathy Study Group (ESSG) submitted to a common protocol of investigation and recruited in 29 reference centers participants of the Brazilian Registry of Spondyloarthritis (RBE - Registro Brasileiro de Espondiloartrites). Patients were divided in two groups: age at onset<16 years (JOSpA group) and age at onset ≥ 16 years (AOSpA group). Among the 1,424 patients, 235 presented disease onset before 16 years (16.5%). The clinical and epidemiologic variables associated with JOSpA were male gender (p<0.001), lower limb arthritis (p=0.001), enthesitis (p=0.008), anterior uveitis (p=0.041) and positive HLA-B27 (p=0.017), associated with lower scores of disease activity (Bath Ankylosing Spondylitis Disease Activity Index - BASDAI; p=0.007) and functionality (Bath Ankylosing Spondylitis Functional Index - BASFI; p=0.036). Cutaneous psoriasis (p<0.001), inflammatory bowel disease (p=0.023), dactylitis (p=0.024) and nail involvement (p=0.004) were more frequent in patients with adult-onset SpA. Patients with JOSpA in this large Brazilian cohort were characterized predominantly by male gender, peripheral involvement (arthritis and enthesitis), positive HLA-B27 and lower disease scores. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Association of chronic obstructive pulmonary disease and hemorrhoids

PubMed Central

Lin, Lih-Hwa; Siu, Justin Ji-Yuen; Liao, Po-Chi; Chiang, Jen-Huai; Chou, Pei-Chi; Chen, Huey-Yi; Ho, Tsung-Jung; Tsai, Ming-Yen; Chen, Yung-Hsiang; Chen, Wen-Chi

2017-01-01

Abstract According to traditional Chinese medicine (TCM) theory, a specific physiological and pathological relationship exists between the lungs and the large intestine. The aim of this study is to delineate the association of chronic obstructive pulmonary disease (COPD) and hemorrhoids in order to verify the “interior–exterior” relationship between the lungs and the large intestine. A retrospective cohort study is conceived from the National Health Insurance Research Database, Taiwan. The 2 samples (COPD cohort and non-COPD cohort) were selected from the 2000 to 2003 beneficiaries of the NHI, representing patients age 20 and older in Taiwan, with the follow-up ending on December 31, 2011. The COPD cohort (n = 51,506) includes every patient newly diagnosed as having Chronic Obstructive Pulmonary Disease (COPD, ICD-9-CM: 490–492, 494, 496), who have made at least 2 confirmed visits to the hospital/clinic. The non-COPD cohort (n = 103,012) includes patients without COPD and is selected via a 1:2 (COPD: non-COPD) matching by age group (per 5 years), gender, and index date (diagnosis date of COPD for the COPD cohort). Compared with non-COPD cohorts, patients with COPD have a higher likelihood of having hemorrhoids and the age-, gender- and comorbidies-adjusted hazard ratio (HR) for hemorrhoids is 1.56 (95% confidence intervals [CI]:1.50–1.62). The adjusted HR of hemorrhoids for females is 0.79 (95% CI: 0.77–0.83), which is significantly less than that for males. The elderly groups, 40 to 59 years and aged 60 or above, have higher adjusted HRs than younger age groups (20–39 years), 1.19 (95% CI: 1.14–1.26), and 1.18 (95% CI: 1.12–1.24), respectively. Patients with COPD may have a higher likelihood to have hemorrhoids in this retrospective cohort study. This study verifies the fundamental theorem of TCM that there is a definite pathogenic association between the lungs and large intestine. PMID:28272246

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.

A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients

PubMed Central

Luo, Fang; Wang, Jin'e; Shi, Yi; Tan, Yu; Chen, Qianlong; Zhang, Yu; Hui, Rutai; Wang, Yibo

2014-01-01

Inconsistent associations with warfarin dose were observed in genetic variants except VKORC1 haplotype and CYP2C9*3 in Chinese people, and few studies on warfarin dose algorithm was performed in a large Chinese Han population lived in Northern China. Of 787 consenting patients with heart-valve replacements who were receiving long-term warfarin maintenance therapy, 20 related Single nucleotide polymorphisms were genotyped. Only VKORC1 and CYP2C9 SNPs were observed to be significantly associated with warfarin dose. In the derivation cohort (n = 551), warfarin dose variability was influenced, in decreasing order, by VKORC1 rs7294 (27.3%), CYP2C9*3(7.0%), body surface area(4.2%), age(2.7%), target INR(1.4%), CYP4F2 rs2108622 (0.7%), amiodarone use(0.6%), diabetes mellitus(0.6%), and digoxin use(0.5%), which account for 45.1% of the warfarin dose variability. In the validation cohort (n = 236), the actual maintenance dose was significantly correlated with predicted dose (r = 0.609, P<0.001). Our algorithm could improve the personalized management of warfarin use in Northern Chinese patients. PMID:25126975

trans Octadecenoic acid and trans octadecadienoic acid are inversely related to long-chain polyunsaturates in human milk: results of a large birth cohort study.

PubMed

Szabó, Eva; Boehm, Günther; Beermann, Christopher; Weyermann, Maria; Brenner, Hermann; Rothenbacher, Dietrich; Decsi, Tamás

2007-05-01

Several observational studies indicate that trans isomeric fatty acids may interfere with the metabolism of essential fatty acids in the human organism. The objective was to investigate the relation between trans fatty acids and long-chain polyunsaturates in mature human milk. Human milk samples (n=769) were obtained at the 6th week of lactation from mothers participating in a birth cohort study in Germany. The fatty acid composition of the milk samples was measured by high-resolution capillary gas-liquid chromatography. trans Octadecenoic and trans octadecadienoic acids were inversely correlated with linoleic acid (r=-0.32 and -0.33, P<0.0001 for both), alpha-linolenic acid (r=-0.35 and -0.27, P<0.0001), arachidonic acid (r=-0.60 and -0.47, P<0.0001), and docosahexaenoic acid (r=-0.51 and -0.33, P<0.0001). In contrast, no inverse correlations were observed between trans hexadecenoic acid and polyunsaturated fatty acids. The data obtained in the present study suggest that the availability of 18-carbon trans isomeric fatty acids may be inversely related to the availability of long-chain polyunsaturated fatty acids in mature human milk.

Dietary habits and risk of urothelial cancer death in a large-scale cohort study (JACC Study) in Japan.

PubMed

Sakauchi, Fumio; Mori, Mitsuru; Washio, Masakazu; Watanabe, Yoshiyuki; Ozasa, Kotaro; Hayashi, Kyohei; Miki, Tsuneharu; Nakao, Masahiro; Mikami, Kazuya; Ito, Yoshinori; Wakai, Kenji; Tamakoshi, Akiko

2004-01-01

In the present study, the associations of dietary habits with the risk of urothelial cancer death were evaluated taking into consideration sex, age, and smoking habits. The Japan Collaborative Cohort Study was established in 1988-1990 and consisted of 47,997 men and 66,520 women observed until the end of 1999. A self-administered food-frequency questionnaire was used as a baseline survey. Hazard ratios for dietary factors were calculated by Cox's proportional hazards model. During the observation period, 63 men and 25 women died of urothelial cancer. Increasing age, male gender, and history of smoking were all significantly associated with increased risk of urothelial cancer death. A high intake of milk and fruits other than oranges reduced the risk significantly and dose dependently, in particular among subjects with smoking history. However, consumption of butter and yogurt had no associations with the risk. Intakes of cabbage, lettuce, green leafy vegetables, carrots, squash, tomatoes, and oranges were not significantly associated with the risk. It was suggested that urothelial cancer death could be potentially preventable by smoking cessation and regular intake of milk and fruit.

Lifestyle and Risk of Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Cohort of United States Male Health Professionals

PubMed Central

Zhang, Ran; Sutcliffe, Siobhan; Giovannucci, Edward; Willett, Walter C.; Platz, Elizabeth A.; Rosner, Bernard A.; Dimitrakoff, Jordan D.; Wu, Kana

2015-01-01

Purpose Although chronic prostatitis/chronic pelvic pain syndrome is a prevalent urological disorder among men of all ages, its etiology remains unknown. Only a few previous studies have examined associations between lifestyle factors and chronic prostatitis/chronic pelvic pain syndrome, of which most were limited by the cross-sectional study design and lack of control for possible confounders. To address these limitations we performed a cohort study of major lifestyle factors (obesity, smoking and hypertension) and chronic prostatitis/chronic pelvic pain syndrome risk in the HPFS (Health Professionals Follow-up Study), a large ongoing cohort of United States based male health professionals. Materials and Methods The HPFS includes 51,529 men who were 40 to 75 years old at baseline in 1986. At enrollment and every 2 years thereafter participants have completed questionnaires on lifestyle and health conditions. In 2008 participants completed an additional set of questions on recent chronic prostatitis/chronic pelvic pain syndrome pain symptoms modified from the NIH (National Institutes of Health)-CPSI (Chronic Prostatitis Symptom Index) as well as questions on approximate date of symptom onset. The 653 participants with NIH-CPSI pain scores 8 or greater who first experienced symptoms after 1986 were considered incident chronic prostatitis/chronic pelvic pain syndrome cases and the 19,138 who completed chronic prostatitis/chronic pelvic pain syndrome questions but did not report chronic prostatitis/chronic pelvic pain syndrome related pain were considered noncases. Results No associations were observed for baseline body mass index, waist circumference, waist-to-hip ratio, cigarette smoking and hypertension with chronic prostatitis/chronic pelvic pain syndrome risk (each OR ≤1.34). Conclusions In this large cohort study none of the lifestyle factors examined was associated with chronic prostatitis/chronic pelvic pain syndrome risk. As the etiology of chronic prostatitis/chronic pelvic pain syndrome remains unknown, additional prospective studies are needed to elucidate modifiable risk factors for this common condition. PMID:26070893

Statin adherence and the risk of Parkinson's disease: A population-based cohort study.

PubMed

Rozani, Violetta; Giladi, Nir; El-Ad, Baruch; Gurevich, Tanya; Tsamir, Judith; Hemo, Beatriz; Peretz, Chava

2017-01-01

While experimental data provided some compelling evidence on the benefits of statins on dopaminergic neurons, observational studies reported conflicting results regarding the potential of statins to effect the risk of Parkinson's disease (PD). To evaluate the association between changes in statin adherence over time and PD risk. A population-based cohort of new statin users (ages 40-79, years 1999-2012) was derived from a large Israeli healthcare services organization. Data included history of statin purchases and low density lipoprotein cholesterol (LDL-C) levels. Personal statin adherence was measured annually by the proportion of days covered (PDC). PD was detected employing a drug-tracer approach. Stratified (by sex, LDL-C levels at baseline and age) Cox proportional hazards models with time-dependent covariates were used to compute adjusted Hazard Ratio (HR) with 95%CI. The cohort included 232,877 individuals, 49.3% men. Mean age at first statin purchase was 56.5 (±9.8) years for men and 58.7 (±9.2) years for women. PDC distribution for the whole follow up period differed between men and women: medians 58.3% and 54.1% respectively. During a mean follow up of 7.6 (±3.4) years, 2,550 (1.1%) PD cases were identified. In a 1-year lagged analysis, we found no association between annual statin adherence and PD risk in all age-groups regardless of statin type and potency. Age-pooled HR (95%CI) for men and women with LDL-C levels at baseline ≤160mg/dL were: 0.99 (0.99-1.01), 1.01 (1.00-1.02); and for men and women with LDL-C >160mg/dL levels: 0.99 (0.98-1.01), 0.97 (0.98-1.01). Our findings suggest that statin adherence over time does not affect PD risk. Future studies should use large-scale cohorts and refining assessments of long-term profiles in statin adherence.

Statistical Models for the Analysis of Zero-Inflated Pain Intensity Numeric Rating Scale Data.

PubMed

Goulet, Joseph L; Buta, Eugenia; Bathulapalli, Harini; Gueorguieva, Ralitza; Brandt, Cynthia A

2017-03-01

Pain intensity is often measured in clinical and research settings using the 0 to 10 numeric rating scale (NRS). NRS scores are recorded as discrete values, and in some samples they may display a high proportion of zeroes and a right-skewed distribution. Despite this, statistical methods for normally distributed data are frequently used in the analysis of NRS data. We present results from an observational cross-sectional study examining the association of NRS scores with patient characteristics using data collected from a large cohort of 18,935 veterans in Department of Veterans Affairs care diagnosed with a potentially painful musculoskeletal disorder. The mean (variance) NRS pain was 3.0 (7.5), and 34% of patients reported no pain (NRS = 0). We compared the following statistical models for analyzing NRS scores: linear regression, generalized linear models (Poisson and negative binomial), zero-inflated and hurdle models for data with an excess of zeroes, and a cumulative logit model for ordinal data. We examined model fit, interpretability of results, and whether conclusions about the predictor effects changed across models. In this study, models that accommodate zero inflation provided a better fit than the other models. These models should be considered for the analysis of NRS data with a large proportion of zeroes. We examined and analyzed pain data from a large cohort of veterans with musculoskeletal disorders. We found that many reported no current pain on the NRS on the diagnosis date. We present several alternative statistical methods for the analysis of pain intensity data with a large proportion of zeroes. Published by Elsevier Inc.

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.

Period effects, cohort effects, and the narrowing gender wage gap.

PubMed

Campbell, Colin; Pearlman, Jessica

2013-11-01

Despite the abundance of sociological research on the gender wage gap, questions remain. In particular, the role of cohorts is under investigated. Using data from the Current Population Survey, we use age-period-cohort analysis to uniquely estimate age, period, and cohort effects on the gender wage gap. The narrowing of the gender wage gap that occurred between 1975 and 2009 is largely due to cohort effects. Since the mid-1990s, the gender wage gap has continued to close absent of period effects. While gains in female wages contributed to declines in the gender wage gap for cohorts born before 1950, for later cohorts the narrowing of the gender wage gap is primarily a result of declines in male wages. Copyright © 2013 Elsevier Inc. All rights reserved.

COHORT EFFECTS OF SUICIDE MORTALITY ARE SEX SPECIFIC IN THE RAPIDLY DEVELOPED HONG KONG CHINESE POPULATION, 1976-2010.

PubMed

Chung, Roger Y; Yip, Benjamin H K; Chan, Sandra S M; Wong, Samuel Y S

2016-06-01

To examine temporal variations of age, period, and cohort on suicide mortality rate in Hong Kong (HK) from 1976 to 2010, and speculate the macroenvironmental mechanisms of the observed trends. Poisson age-period-cohort modeling was used to delineate the effects of age, period, and cohort on suicide mortality. Analysis by sex was also conducted to examine if gender difference exists for suicidal behaviours. Age-cohort model provides the best fit to the mortality data, implying that the cohort effect is likely to explain more of the contributions to HK's suicide mortality pattern than the period effect. Risk of suicide mortality increases nonlinearly with age and accelerates after age 65-69 for both sexes. Moreover, the cohort effects differ between the sexes-risk of mortality increases continually for men born after 1961, but no change is observed for women since the 1941 cohort. With increased risk of suicide mortality in younger cohorts and the age effect of suicide mortality, we may see future increase in suicide mortality as these younger cohorts age. Further studies are needed to clarify plausible associations between broader sociohistorical changes in the population impacting psychological risk factors and suicidal behaviour to better inform suicide prevention strategies. © 2015 Wiley Periodicals, Inc.

Cohort profile: the Geoscience and Health Cohort Consortium (GECCO) in the Netherlands

PubMed Central

Timmermans, Erik J; Lakerveld, Jeroen; Beulens, Joline W J; Boomsma, Dorret I; Kramer, Sophia E; Oosterman, Mirjam; Willemsen, Gonneke; Stam, Mariska; Nijpels, Giel; Schuengel, Carlo; Smit, Jan H; Brunekreef, Bert; Dekkers, Jasper E C; Deeg, Dorly J H; Penninx, Brenda W J H; Huisman, Martijn

2018-01-01

Purpose In the Netherlands, a great variety of objectively measured geo-data is available, but these data are scattered and measured at varying spatial and temporal scales. The centralisation of these geo-data and the linkage of these data to individual-level data from longitudinal cohort studies enable large-scale epidemiological research on the impact of the environment on public health in the Netherlands. In the Geoscience and Health Cohort Consortium (GECCO), six large-scale and ongoing cohort studies have been enriched with a variety of existing geo-data. Here, we introduce GECCO by describing: (1) the phenotypes of the involved cohort studies, (2) the collected geo-data and their sources, (3) the methodology that was used to link the collected geo-data to individual cohort studies, (4) the similarity of commonly used geo-data between our consortium and the nationwide situation in the Netherlands and (5) the distribution of geo-data within our consortium. Participants GECCO includes participants from six prospective cohort studies (eg, 44 657 respondents (18–100 years) in 2006) and it covers all municipalities in the Netherlands. Using postal code information of the participants, geo-data on the address-level, postal code-level as well as neighbourhood-level could be linked to individual-level cohort data. Findings to date The geo-data could be successfully linked to almost all respondents of all cohort studies, with successful data-linkage rates ranging from 97.1% to 100.0% between cohort studies. The results show variability in geo-data within and across cohorts. GECCO increases power of analyses, provides opportunities for cross-checking and replication, ensures sufficient geographical variation in environmental determinants and allows for nuanced analyses on specific subgroups. Future plans GECCO offers unique opportunities for (longitudinal) studies on the complex relationships between the environment and health outcomes. For example, GECCO will be used for further research on environmental determinants of physical/psychosocial functioning and lifestyle behaviours. PMID:29886447

Increased dementia risk predominantly in diabetes mellitus rather than in hypertension or hyperlipidemia: a population-based cohort study.

PubMed

Fan, Yen-Chun; Hsu, Jung-Lung; Tung, Hong-Yi; Chou, Chia-Chi; Bai, Chyi-Huey

2017-02-06

The pathophysiology of insulin resistance-induced hypertension and hyperlipidemia might entail differences in dementia risk in cases with hypertension and hyperlipidemia without prior diabetes mellitus (DM). This study investigated whether incident hypertension, incident hyperlipidemia, or both, increased the dementia risk in patients with and without DM. A nationwide retrospective cohort study was conducted. The study sample was obtained from the National Health Insurance Research Database. We enrolled 10,316 patients with a new diagnosis of DM between 2000 and 2002 in the DM cohort. For the same period, we randomly selected 41,264 patients without DM in the non-DM cohort (matched by age and sex at a 1:4 ratio with the DM cohort). Both cohorts were then separately divided into four groups on the basis of incident hypertension or incident hyperlipidemia status. In total, 51,580 patients aged between 20 and 99 years were enrolled. The dementia risk was higher in the DM cohort than in the non-DM cohort (adjusted hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.30-1.67, p < 0.001). In the DM cohort, the dementia risk in patients with both hypertension and hyperlipidemia did not significantly increase compared with that in those without hypertension and hyperlipidemia (p = 0.529). Similar results were observed in those with either hypertension (p = 0.341) or hyperlipidemia (p = 0.189). In the non-DM cohort, patients with both hypertension and hyperlipidemia had a higher dementia risk (adjusted HR = 1.33, 95% CI = 1.09-1.63, p = 0.006). The results remained largely unchanged in patients with only hypertension (adjusted HR = 1.22, 95% CI = 1.05-1.40, p = 0.008). However, the dementia risk did not increase significantly in patients with only hyperlipidemia (p = 0.187). The development of hypertension, hyperlipidemia, or both, following a diagnosis of incident diabetes is secondary to diabetes onset and likely mediated through insulin resistance associated with diabetes, which does not further accentuate dementia risk. DM itself (i.e., the systemic influence of hyperglycemia) might be the main driver of increased dementia risk.

Description of cervical cancer mortality in Belgium using Bayesian age-period-cohort models

PubMed Central

2009-01-01

Objective To correct cervical cancer mortality rates for death cause certification problems in Belgium and to describe the corrected trends (1954-1997) using Bayesian models. Method Cervical cancer (cervix uteri (CVX), corpus uteri (CRP), not otherwise specified (NOS) uterus cancer and other very rare uterus cancer (OTH) mortality data were extracted from the WHO mortality database together with population data for Belgium and the Netherlands. Different ICD (International Classification of Diseases) were used over time for death cause certification. In the Netherlands, the proportion of not-otherwise specified uterine cancer deaths was small over large periods and therefore internal reallocation could be used to estimate the corrected rates cervical cancer mortality. In Belgium, the proportion of improperly defined uterus deaths was high. Therefore, the age-specific proportions of uterus cancer deaths that are probably of cervical origin for the Netherlands was applied to Belgian uterus cancer deaths to estimate the corrected number of cervix cancer deaths (corCVX). A Bayesian loglinear Poisson-regression model was performed to disentangle the separate effects of age, period and cohort. Results The corrected age standardized mortality rate (ASMR) decreased regularly from 9.2/100 000 in the mid 1950s to 2.5/100,000 in the late 1990s. Inclusion of age, period and cohort into the models were required to obtain an adequate fit. Cervical cancer mortality increases with age, declines over calendar period and varied irregularly by cohort. Conclusion Mortality increased with ageing and declined over time in most age-groups, but varied irregularly by birth cohort. In global, with some discrete exceptions, mortality decreased for successive generations up to the cohorts born in the 1930s. This decline stopped for cohorts born in the 1940s and thereafter. For the youngest cohorts, even a tendency of increasing risk of dying from cervical cancer could be observed, reflecting increased exposure to risk factors. The fact that this increase was limited for the youngest cohorts could be explained as an effect of screening. Bayesian modeling provided similar results compared to previously used classical Poisson models. However, Bayesian models are more robust for estimating rates when data are sparse (youngest age groups, most recent cohorts) and can be used to for predicting future trends.

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.

The effect of vildagliptin relative to sulfonylurea as dual therapy with metformin (or as monotherapy) in Muslim patients with type 2 diabetes fasting during Ramadan in the Middle East: the VIRTUE study.

PubMed

Hassoun, Ahmed A K; Al-Arouj, Monira; Ibrahim, Mohamed

2017-01-01

To assess the effect of vildagliptin relative to sulfonylurea (SU) on hypoglycemic events, in Muslim patients from the Middle East with type 2 diabetes who fast during Ramadan. The primary endpoint was the proportion of patients with at least one hypoglycemic event (HE) during the fasting period. Secondary endpoints included change in weight, HbA1c levels, treatment adherence and overall safety. This multicenter, prospective, observational cohort study enrolled Muslim adult T2DM patients from Middle Eastern countries who received treatment with vildagliptin or SU as add on to metformin or monotherapy. During a ∼16 week observation period, data was collected up to 6 weeks before and 6 weeks after Ramadan fasting. A total of 584 patients from the Middle East enrolled in the study; 308 patients received vildagliptin and 265 received SU. Significantly fewer vildagliptin patients reported at least one HE (3.7% vildagliptin vs. 25.5% SU; p < .001). No grade 2 HEs were reported in vildagliptin patients versus two in SU patients (p = .128). Mean change in HbA1c at the end of study showed -0.18% between treatment difference in favor of vildagliptin, p = .001. Mean body weight change at the end of study showed -0.68 kg between treatment difference in favor of vildagliptin, p < .001. Treatment exposure and adherence were high and similar in both cohorts. There were 4.3% adverse events reported in vildagliptin compared to 25.3% in the SU cohort, with hypoglycemia being the most experienced event in both cohorts. Being observational and not mandating HE confirmation with blood glucose measurement (though it was done in a large number of patients) were key limitations. Anti-hyperglycemic treatment with vildagliptin led to significantly fewer hypoglycemia events compared to sulfonylurea treatment among Muslim diabetic patients who fast during Ramadan. Good glycemic control, weight control and safety results supported this outcome.

Understanding attrition from international Internet health interventions: a step towards global eHealth.

PubMed

Geraghty, Adam W A; Torres, Leandro D; Leykin, Yan; Pérez-Stable, Eliseo J; Muñoz, Ricardo F

2013-09-01

Worldwide automated Internet health interventions have the potential to greatly reduce health disparities. High attrition from automated Internet interventions is ubiquitous, and presents a challenge in the evaluation of their effectiveness. Our objective was to evaluate variables hypothesized to be related to attrition, by modeling predictors of attrition in a secondary data analysis of two cohorts of an international, dual language (English and Spanish) Internet smoking cessation intervention. The two cohorts were identical except for the approach to follow-up (FU): one cohort employed only fully automated FU (n = 16 430), while the other cohort also used 'live' contact conditional upon initial non-response (n = 1000). Attrition rates were 48.1 and 10.8% for the automated FU and live FU cohorts, respectively. Significant attrition predictors in the automated FU cohort included higher levels of nicotine dependency, lower education, lower quitting confidence and receiving more contact emails. Participants' younger age was the sole predictor of attrition in the live FU cohort. While research on large-scale deployment of Internet interventions is at an early stage, this study demonstrates that differences in attrition from trials on this scale are (i) systematic and predictable and (ii) can largely be eliminated by live FU efforts. In fully automated trials, targeting the predictors we identify may reduce attrition, a necessary precursor to effective behavioral Internet interventions that can be accessed globally.

Measles, Rubella and Varicella IgG Seroprevalence in a Large Refugee Cohort in Germany in 2015: A Cross-Sectional Study.

PubMed

Jablonka, Alexandra; Happle, Christine; Wetzke, Martin; Dopfer, Christian; Merkesdal, Sonja; Schmidt, Reinhold E; Behrens, Georg M N; Solbach, Philipp

2017-12-01

The current extent of migration to the European continent is associated with exceptional humanitarian challenges. In 2015, Western Europe faced an enormous immigration of refugees with largely unknown protection status against communicable diseases. To adapt vaccination strategies, we aimed at assessing seroprevalences against three of the most relevant vaccine preventable diseases (VPD) in a large representative cohort. IgG seroprevalences for rubella, varicella (n = 554) and measles (n = 552) were analyzed in inhabitants of a Northern German refugee camp in the summer of 2015. Of the refugees, 77.9% were male (mean age 27.4 years for male and 26.8 years for female migrants). Most refugees came from the Eastern Mediterranean region (83.4%), followed by immigrants from Eastern Europe (7.4%), Africa (4.6%), or other regions (4.5%). The vast majority of migrants were protected against the three VPD: overall IgG seropositivity was 88.5% for measles, 77.9% for rubella and 95.9% for varicella. However, seroprevalences showed age- and origin-dependent differences. Varicella immunity, for example, was lowest in the youngest age group of both genders (10.1% of male/4.5% of female seronegative refugees <18 years vs. 100% seropositivity in men and women >49 years of age), and Sudanese migrants displayed particularly low rates of protection against varicella. In accordance with previous studies, our analyses show an overall satisfactory seropositivity against measles, rubella, and varicella in refugees entering Europe during the current exodus. However, this rate is not sufficient for preventing transmission. For example, the rate of 12.9-17.9% female refugees at reproductive age unprotected against measles and the low protection levels against varicella in minors observed in our cohort emphasizes the need for stringent vaccination strategies in refugees coming to Europe during the current crisis.

High efficacy of Sofosbuvir plus Simeprevir in a large cohort of Spanish cirrhotic patients infected with genotypes 1 and 4.

PubMed

Mariño, Zoe; Pascasio-Acevedo, Juan M; Gallego, Adolfo; Diago, Moisés; Baliellas, Carme; Morillas, Rosa; Prieto, Martín; Moreno, José M; Sánchez-Antolín, Gloria; Vergara, Mercedes; Forné, Montserrat; Fernández, Inmaculada; Castro, María A; Pascual, Sonia; Gómez, Alexandra; Castells, Lluis; Montero, José L; Crespo, Javier; Calleja, José L; García-Samaniego, Javier; Carrión, Jose A; Arencibia, Ana C; Blasco, Alejandro; López-Núñez, Carmen; Sánchez-Ruano, Juan J; Gea-Rodríguez, Francisco; Giráldez, Álvaro; Cabezas, Joaquín; Hontangas, Vanessa; Torras, Xavier; Castellote, Jose; Romero-Gómez, Manuel; Turnes, Juan; de Artaza, Tomás; Narváez, Isidoro; Cuervas-Mons, Valentín; Forns, Xavier

2017-12-01

Hepatitis C (HCV) therapy with Sofosbuvir (SOF)/Simeprevir (SMV) in clinical trials and real-world clinical practice, showed high rates of sustained virological response (SVR) in non-cirrhotic genotype (GT)-1 and GT-4 patients. These results were slightly lower in cirrhotic patients. We investigated real-life effectiveness and safety of SOF/SMV with or without ribavirin (RBV) in a large cohort of cirrhotic patients. This collaborative multicentre study included data from 968 patients with cirrhosis infected with HCV-GT1 or 4, treated with SOF/SMV±RBV in 30 centres across Spain between January-2014 and December-2015. Demographic, clinical, virological and safety data were analysed. Overall SVR was 92.3%; the majority of patients were treated with RBV (62%) for 12 weeks (92.4%). No significant differences in SVR were observed between genotypes (GT1a:94.3%; GT1b:91.7%; GT4:91.1%). Those patients with more advanced liver disease (Child B/C, MELD≥10) or portal hypertension (platelet count≤100×10 9 /L, transient elastography≥21 Kpa) showed significantly lower SVR rates (84.4%-91.9%) than patients with less advanced liver disease (93.8%-95.9%, P<.01 in all cases). In the multivariate analysis, the use of RBV, female gender, baseline albumin≥35 g/L, MELD<10 and lack of exposure to a triple therapy regimen were independent predictors of SVR (P<.05). Serious adverse events (SAEs) and SAE-associated discontinuation events occurred in 5.9% and 2.6%. In this large cohort of cirrhotic patients managed in the real-world setting in Spain, SOF/SMV±RBV yielded to excellent SVR rates, especially in patients with compensated liver cirrhosis. In addition, this combination showed to be safe, with low rates of SAEs and early discontinuations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development and validation of a rebinner with rigid motion correction for the Siemens PET-MR scanner: Application to a large cohort of [11C]-PIB scans.

PubMed

Reilhac, Anthonin; Merida, Ines; Irace, Zacharie; Stephenson, Mary; Weekes, Ashley; Chen, Christopher; Totman, John; Townsend, David W; Fayad, Hadi; Costes, Nicolas

2018-04-13

Objective: Head motion occuring during brain PET studies leads to image blurring and to bias in measured local quantities. Our first objective was to implement an accurate list-mode-based rigid motion correction method for PET data acquired with the mMR synchronous Positron Emission Tomography/Magnetic Resonance (PET/MR) scanner. Our second objective was to optimize the correction for [ 11 C]-PIB scans using simulated and actual data with well-controlled motions. Results: An efficient list-mode based motion correction approach has been implemented, fully optimized and validated using simulated as well as actual PET data. The average spatial resolution loss induced by inaccuracies in motion parameter estimates as well as by the rebinning process was estimated to correspond to a 1 mm increase in Full Width Half Maximum (FWHM) with motion parameters estimated directly from the PET data with a temporal frequency of 20 secs. The results show that it can be safely applied to the [ 11 C]-PIB scans, allowing almost complete removal of motion induced artifacts.The application of the correction method on a large cohort of 11C-PIB scans led to the following observations: i) more than 21% of the scans were affected by a motion greater than 10 mm (39% for subjects with Mini-Mental State Examination -MMSE scores below 20) and ii), the correction led to quantitative changes in Alzheimer-specific cortical regions of up to 30%. Conclusion: The rebinner allows an accurate motion correction at a cost of minimal resolution reduction. The application of the correction to a large cohort of [ 11 C]-PIB scans confirmed the necessity to systematically correct for motion for quantitative results. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Identifying genetic variants that affect viability in large cohorts

PubMed Central

Berisa, Tomaz; Day, Felix R.; Perry, John R. B.

2017-01-01

A number of open questions in human evolutionary genetics would become tractable if we were able to directly measure evolutionary fitness. As a step towards this goal, we developed a method to examine whether individual genetic variants, or sets of genetic variants, currently influence viability. The approach consists in testing whether the frequency of an allele varies across ages, accounting for variation in ancestry. We applied it to the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort and to the parents of participants in the UK Biobank. Across the genome, we found only a few common variants with large effects on age-specific mortality: tagging the APOE ε4 allele and near CHRNA3. These results suggest that when large, even late-onset effects are kept at low frequency by purifying selection. Testing viability effects of sets of genetic variants that jointly influence 1 of 42 traits, we detected a number of strong signals. In participants of the UK Biobank of British ancestry, we found that variants that delay puberty timing are associated with a longer parental life span (P~6.2 × 10−6 for fathers and P~2.0 × 10−3 for mothers), consistent with epidemiological studies. Similarly, variants associated with later age at first birth are associated with a longer maternal life span (P~1.4 × 10−3). Signals are also observed for variants influencing cholesterol levels, risk of coronary artery disease (CAD), body mass index, as well as risk of asthma. These signals exhibit consistent effects in the GERA cohort and among participants of the UK Biobank of non-British ancestry. We also found marked differences between males and females, most notably at the CHRNA3 locus, and variants associated with risk of CAD and cholesterol levels. Beyond our findings, the analysis serves as a proof of principle for how upcoming biomedical data sets can be used to learn about selection effects in contemporary humans. PMID:28873088

Seed distribution of four co-occurring grasses around Artemisia halodendron shrubs in a sandy habitat

NASA Astrophysics Data System (ADS)

Li, Feng-Rui; Zhao, Wen-Zhi; Kang, Ling-Fen; Liu, Ji-Liang; Huang, Zhi-Gang; Wang, Qi

2009-05-01

In a natural population of the perennial semi-shrub Artemisia halodendron in a shifting sandy habitat in the Horqin Desert of eastern Inner Mongolia, six isolated adult A. halodendron individuals of similar canopy size were chosen as target plants. The density of seeds in the top 5 cm soil depth around shrubs was measured using transects aligned to the four main wind directions and at different distances from the shrub base on both the windward and leeward sides. The effects of shrub presence on seed distribution of four co-occurring grasses were examined by linking seed distribution to seed traits. Of the four species, Setaris viridis and Eragrostis pilosa had small but similar seed mass, while Chloris virgata and Aristida adscensionis had large but similar seed mass. The species were grouped into two cohorts: small-seeded vs. large-seeded cohorts, and shrub presence effects on seed distribution of both cohorts were examined. We found marked difference in the seed distribution pattern among species, especially between the small-seeded and large-seeded cohorts. The small-seeded cohort had significantly higher seed accumulation on the windward than the leeward sides in the most and least prevailing wind directions and much higher seed accumulation on the leeward than the windward sides in the second and third most prevailing wind directions, while opposite patterns occurred in the large-seeded cohort. Four species also showed marked variation in the seed distribution pattern among transects and between windward and leeward sides of each transect. This study provided further evidence that shrubs embedded in a matrix of herbaceous plants is a key cause of spatial heterogeneity in seed availability of herbaceous species. However, seed distribution responses to the presence of shrubs will vary with species as well as with wind direction, sampling position (windward vs. leeward sides of the shrub) and distance from the shrub.

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

PubMed Central

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

2013-01-01

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

The Association Between Arthralgia and Vedolizumab Using Natural Language Processing.

PubMed

Cai, Tianrun; Lin, Tzu-Chieh; Bond, Allison; Huang, Jie; Kane-Wanger, Gwendolyn; Cagan, Andrew; Murphy, Shawn N; Ananthakrishnan, Ashwin N; Liao, Katherine P

2018-05-26

The gut-selective nature of vedolizumab has raised questions regarding increased joint pain or arthralgia with its use in inflammatory bowel disease (IBD) patients. As arthralgias are seldom coded and thus difficult to study, few studies have examined the comparative risk of arthralgia between vedolizumab and tumor necrosis factor inhibitor (TNFi). Our objectives were to evaluate the application of natural language processing (NLP) to identify arthralgia in the clinical notes and to compare the risk of arthralgia between vedolizumab and TNFi in IBD. We performed a retrospective study using a validated electronic medical record (EMR)-based IBD cohort from 2 large tertiary care centers. The index date was the first date of vedolizumab or TNFi prescription. Baseline covariates were assessed 1 year before the index date; patients were followed 1 year after the index date. The primary outcome was arthralgia, defined using NLP. Using inverse probability of treatment weight to balance the cohorts, we then constructed Cox regression models to calculate the hazard ratio (HR) for arthralgia in the vedolizumab and TNFi groups. We studied 367 IBD patients on vedolizumab and 1218 IBD patients on TNFi. Patients on vedolizumab were older (mean age, 41.2 vs 34.9 years) and had more prevalent use of immunomodulators (52.3% vs 31.9%) than TNFi users. Our data did not observe a significantly increased risk of arthralgia in the vedolizumab group compared with TNFi (HR, 1.20; 95% confidence interval, 0.97-1.49). In this large observational study, we did not find a significantly increased risk of arthralgia associated with vedolizumab use compared with TNFi.

Cardiac and renal function in a large cohort of amateur marathon runners.

PubMed

Hewing, Bernd; Schattke, Sebastian; Spethmann, Sebastian; Sanad, Wasiem; Schroeckh, Sabrina; Schimke, Ingolf; Halleck, Fabian; Peters, Harm; Brechtel, Lars; Lock, Jürgen; Baumann, Gert; Dreger, Henryk; Borges, Adrian C; Knebel, Fabian

2015-03-21

Participation of amateur runners in endurance races continues to increase. Previous studies of marathon runners have raised concerns about exercise-induced myocardial and renal dysfunction and damage. In our pooled analysis, we aimed to characterize changes of cardiac and renal function after marathon running in a large cohort of mostly elderly amateur marathon runners. A total of 167 participants of the Berlin-Marathon (female n = 89, male n = 78; age = 50.3 ± 11.4 years) were included and cardiac and renal function was analyzed prior to, immediately after and 2 weeks following the race by echocardiography and blood tests (including cardiac troponin T, NT-proBNP and cystatin C). Among the runners, 58% exhibited a significant increase in cardiac biomarkers after completion of the marathon. Overall, the changes in echocardiographic parameters for systolic or diastolic left and right ventricular function did not indicate relevant myocardial dysfunction. Notably, 30% of all participants showed >25% decrease in cystatin C-estimated glomerular filtration rate (GFR) from baseline directly after the marathon; in 8%, we observed a decline of more than 50%. All cardiac and renal parameters returned to baseline ranges within 2 weeks after the marathon. The increase in cardiac biomarkers after completing a marathon was not accompanied by relevant cardiac dysfunction as assessed by echocardiography. After the race, a high proportion of runners experienced a decrease in cystatin C-estimated GFR, which is suggestive of transient, exercise-related alteration of renal function. However, we did not observe persistent detrimental effects on renal function.

Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis.

PubMed

Bezemer, Daniela; Cori, Anne; Ratmann, Oliver; van Sighem, Ard; Hermanides, Hillegonda S; Dutilh, Bas E; Gras, Luuk; Rodrigues Faria, Nuno; van den Hengel, Rob; Duits, Ashley J; Reiss, Peter; de Wolf, Frank; Fraser, Christophe

2015-11-01

The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently introduced clusters. The mean age of MSM at diagnosis increased by 0.45 years/year within clusters, but new clusters appeared with lower mean age. Major strengths of this study are the high proportion of HIV-positive MSM with a sequence in this study and the combined application of phylogenetic and modeling approaches. Main limitations are the assumption that the sampled population is representative of the overall HIV-positive population and the assumption that the diagnosis interval distribution is similar between clusters. The resurgent HIV epidemic amongst MSM in the Netherlands is driven by several large, persistent, self-sustaining, and, in many cases, growing sub-epidemics shifting towards new generations of MSM. Many of the sub-epidemics have been present since the early epidemic, to which new sub-epidemics are being added.

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

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.

Cohort Profile: The International Childhood Cardiovascular Cohort (i3C) Consortium

PubMed Central

Dwyer, Terence; Sun, Cong; Magnussen, Costan G; Raitakari, Olli T; Schork, Nicholas J; Venn, Alison; Burns, Trudy L; Juonala, Markus; Steinberger, Julia; Sinaiko, Alan R; Prineas, Ronald J; Davis, Patricia H; Woo, Jessica G; Morrison, John A; Daniels, Stephen R; Chen, Wei; Srinivasan, Sathanur R; Viikari, Jorma SA; Berenson, Gerald S

2013-01-01

This is a consortium of large children's cohorts that contain measurements of major cardiovascular disease (CVD) risk factors in childhood and had the ability to follow those cohorts into adulthood. The purpose of this consortium is to enable the pooling of data to increase power, most importantly for the follow-up of CVD events in adulthood. Within the consortium, we hope to be able to obtain data on the independent effects of childhood and early adult levels of CVD risk factors on subsequent CVD occurrence. PMID:22434861

The Origins of Cognitive Deficits in Victimized Children: Implications for Neuroscientists and Clinicians.

PubMed

Danese, Andrea; Moffitt, Terrie E; Arseneault, Louise; Bleiberg, Ben A; Dinardo, Perry B; Gandelman, Stephanie B; Houts, Renate; Ambler, Antony; Fisher, Helen L; Poulton, Richie; Caspi, Avshalom

2017-04-01

Individuals reporting a history of childhood violence victimization have impaired brain function. However, the clinical significance, reproducibility, and causality of these findings are disputed. The authors used data from two large cohort studies to address these research questions directly. The authors tested the association between prospectively collected measures of childhood violence victimization and cognitive functions in childhood, adolescence, and adulthood among 2,232 members of the U.K. E-Risk Study and 1,037 members of the New Zealand Dunedin Study who were followed up from birth until ages 18 and 38 years, respectively. Multiple measures of victimization and cognition were used, and comparisons were made of cognitive scores for twins discordant for victimization. Individuals exposed to childhood victimization had pervasive impairments in clinically relevant cognitive functions, including general intelligence, executive function, processing speed, memory, perceptual reasoning, and verbal comprehension in adolescence and adulthood. However, the observed cognitive deficits in victimized individuals were largely explained by cognitive deficits that predated childhood victimization and by confounding genetic and environmental risks. Findings from two population-representative birth cohorts totaling more than 3,000 individuals and born 20 years and 20,000 km apart suggest that the association between childhood violence victimization and later cognition is largely noncausal, in contrast to conventional interpretations. These findings support the adoption of a more circumspect approach to causal inference in the neuroscience of stress. Clinically, cognitive deficits should be conceptualized as individual risk factors for victimization as well as potential complicating features during treatment.

Integrated Database And Knowledge Base For Genomic Prospective Cohort Study In Tohoku Medical Megabank Toward Personalized Prevention And Medicine.

PubMed

Ogishima, Soichi; Takai, Takako; Shimokawa, Kazuro; Nagaie, Satoshi; Tanaka, Hiroshi; Nakaya, Jun

2015-01-01

The Tohoku Medical Megabank project is a national project to revitalization of the disaster area in the Tohoku region by the Great East Japan Earthquake, and have conducted large-scale prospective genome-cohort study. Along with prospective genome-cohort study, we have developed integrated database and knowledge base which will be key database for realizing personalized prevention and medicine.

SSRIs and risk of suicide attempts in young people - A Danish observational register-based historical cohort study, using propensity score.

PubMed

Christiansen, Erik; Agerbo, Esben; Bilenberg, Niels; Stenager, Elsebeth

2016-01-01

SSRIs are widely used in the treatment of mental illness for both children and adults. Studies have found a slightly increased risk of suicidal thoughts and suicide attempts in young people using SSRIs but SSRIs' impact on risk for suicides in youth is not well-established. Is there indication that SSRIs might raise risk for suicide attempts in young people? We used an observational register-based historical cohort design, a large cohort of all Danish individuals born in 1983-1989 (n = 392,458) and a propensity score approach to analyse the impact from SSRIs on risk for suicide attempts. Every suicide attempt and redeemed prescription of SSRIs was analysed by Cox regression. We found a significant overlap between redeeming a prescription on SSRIs and subsequent suicide attempt. The risk for suicide attempt was highest in the first 3 months after redeeming the first prescription. The hazard ratio for suicide attempts after redeeming a prescription was estimated to 5.23, 95% CI 4.82-5.68. We conclude that the risk of suicide attempt is higher for young people in the first months after redeeming their first prescription for SSRIs, compared to non-users. For SSRI users with lower propensity score (fewer risk factors for SSRIs) the risk of suicide attempt is estimated to be highest. Although the design may miss some explicit reason for prescription of SSRIs and SSRIs might be a marker for those in high risk rather than a causal risk factor, we would recommend systematic risk assessment in the period after redeeming the first prescription.

Cancer incidence among Danish Seventh-day Adventists and Baptists.

PubMed

Thygesen, Lau Caspar; Hvidt, Niels Christian; Hansen, Helle Ploug; Hoff, Andreas; Ross, Lone; Johansen, Christoffer

2012-12-01

American Seventh-day Adventists have been reported to have lower cancer mortality and incidence than the general population. Adventists do not consume tobacco, alcohol or pork, and many adhere to a lacto-ovo-vegetarian lifestyle. Baptists discourage excessive use of alcohol and tobacco. In this study, we investigated whether the incidence of cancer in a large cohort of Danish Adventists and Baptists was different compared to the general Danish population. We followed 11,580 Danish Adventists and Baptists in the nationwide Danish Cancer Registry, which contains information on cases of cancer for 1943-2008. Cancer incidence in the cohort was compared with that in the general Danish population as standardized incidence ratios (SIRs) with 95% confidence intervals (CIs), and within-cohort comparisons were made with a Cox model. Lower cancer incidences were observed for both Seventh-day Adventist men (SIR, 66; 95% CI, 60-72) and women (85; 80-91). The same result was observed for Baptists although not as low. The differences were most pronounced for smoking-related cancers such as those of the buccal cavity and lung (SIR, 20; 13-30 for Seventh-day Adventist men and 33; 22-49 for Seventh-day Adventist women). The incidences of other lifestyle-related cancers, such as of stomach, rectum, liver and cervix, were also decreased. In general, the SIRs were lower for men than for women, and Adventists had lower hazard rates than Baptists. Our findings point to the benefits of compliance with public health recommendations and indicate that lifestyle changes in the population might change the cancer risks of individuals. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Impact of HIV Co-Infection on the Genomic Response to Sepsis

PubMed Central

Huson, Michaëla A. M.; Scicluna, Brendon P.; van Vught, Lonneke A.; Wiewel, Maryse A.; Hoogendijk, Arie J.; Cremer, Olaf L.; Bonten, Marc J. M.; Schultz, Marcus J.; Franitza, Marek; Toliat, Mohammad R.; Nürnberg, Peter; Grobusch, Martin P.; van der Poll, Tom

2016-01-01

HIV patients have an increased risk to develop sepsis and HIV infection affects several components of the immune system involved in sepsis pathogenesis. We hypothesized that HIV infection might aggrevate the aberrant immune response during sepsis, so we aimed to determine the impact of HIV infection on the genomic host response to sepsis. We compared whole blood leukocyte gene expression profiles among sepsis patients with or without HIV co-infection in the intensive care unit (ICU) and validated our findings in a cohort of patients admitted to the same ICUs in a different time frame. To examine the influence of HIV infection per se, we also determined the expression of genes of interest in a cohort of asymptomatic HIV patients. We identified a predominantly common host response in sepsis patients with or without HIV co-infection. HIV positive sepsis patients in both ICU cohorts showed overexpression of genes involved in granzyme signaling (GZMA, GZMB), cytotoxic T-cell signaling (CD8A, CD8B) and T-cell inhibitory signaling (LAG3), compared to HIV negative patients. Enhanced expression of CD8A, CD8B and LAG3 was also unmasked in asymptomatic HIV patients. Plasma levels of granzymes in sepsis patients were largely below detection limit, without differences according to HIV status. These results demonstrate that sepsis is characterized by a massive common response with few differences between HIV positive and HIV negative sepsis patients. Observed differences in granzyme signaling, cytotoxic T-cell signaling and T-cell inhibitory signaling appear to be changes commonly observed in asymptomatic HIV patients which persist during sepsis. PMID:26871709

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.

OVERWEIGHT/OBESITY AND HUMAN CAPITAL FORMATION FROM INFANCY TO ADOLESCENCE: EVIDENCE FROM TWO LARGE US COHORTS.

PubMed

Murasko, Jason E

2015-03-01

Body mass index (BMI) levels in US children and adolescents have increased over the past several decades. The negative health effects of this trend are well-documented. Recent work has evaluated the potential effects on skills formation. Studies are mixed on whether there is an association between high BMI and skills outcomes, and those that estimate causal effects find none. This paper offers estimates on the causal effect of BMI-defined overweight and obesity on skills formation using two large cohorts of contemporary US children followed from infancy to 5 years and from kindergarten (6 years) to the eighth grade (14 years). Significant negative associations were observed in the random effects models for males in early life with respect to a mental skills assessment, for females during the pre-school years for reading and maths assessments, for both males and females during the schooling years for reading assessments and for females during the schooling years for maths assessments. Fixed effects models yielded a significant negative association only with respect to the latter. The implication of these findings is that any improvement in skills outcomes that may accompany reductions in obesity prevalence may depend on whether interventions are general to overall health productivity or whether they are specific to dietary and exercise behaviours.

SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids

DOE PAGES

Zhang, Xing; Romm, Michelle; Zheng, Xueyun; ...

2016-12-29

Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here in this article, we present a novel platform for small molecule analyses that addresses these requirements by combining solid-phase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS). This platform is capable of performing both targeted and global measurements of endogenous metabolites and xenobiotics in human biofluids with highmore » reproducibility (CV ≤ 3%), sensitivity (LODs in the pM range in biofluids) and throughput (10-s sample-to-sample duty cycle). We report application of this platform to the analysis of human urine from patients with and without type 1 diabetes, where we observed statistically significant variations in the concentration of disaccharides and previously unreported chemical isomers. Lastly, this SPE-IMS-MS platform overcomes many of the current challenges of large-scale metabolomic and exposomic analyses and offers a viable option for population and patient cohort screening in an effort to gain insights into disease processes and human environmental chemical exposure.« less

SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids.

PubMed

Zhang, Xing; Romm, Michelle; Zheng, Xueyun; Zink, Erika M; Kim, Young-Mo; Burnum-Johnson, Kristin E; Orton, Daniel J; Apffel, Alex; Ibrahim, Yehia M; Monroe, Matthew E; Moore, Ronald J; Smith, Jordan N; Ma, Jian; Renslow, Ryan S; Thomas, Dennis G; Blackwell, Anne E; Swinford, Glenn; Sausen, John; Kurulugama, Ruwan T; Eno, Nathan; Darland, Ed; Stafford, George; Fjeldsted, John; Metz, Thomas O; Teeguarden, Justin G; Smith, Richard D; Baker, Erin S

2016-12-01

Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here, we present a novel platform for small molecule analyses that addresses these requirements by combining solid-phase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS). This platform is capable of performing both targeted and global measurements of endogenous metabolites and xenobiotics in human biofluids with high reproducibility (CV 6 3%), sensitivity (LODs in the pM range in biofluids) and throughput (10-s sample-to-sample duty cycle). We report application of this platform to the analysis of human urine from patients with and without type 1 diabetes, where we observed statistically significant variations in the concentration of disaccharides and previously unreported chemical isomers. This SPE-IMS-MS platform overcomes many of the current challenges of large-scale metabolomic and exposomic analyses and offers a viable option for population and patient cohort screening in an effort to gain insights into disease processes and human environmental chemical exposure.

Effect of in-painting on cortical thickness measurements in multiple sclerosis: A large cohort study.

PubMed

Govindarajan, Koushik A; Datta, Sushmita; Hasan, Khader M; Choi, Sangbum; Rahbar, Mohammad H; Cofield, Stacey S; Cutter, Gary R; Lublin, Fred D; Wolinsky, Jerry S; Narayana, Ponnada A

2015-10-01

A comprehensive analysis of the effect of lesion in-painting on the estimation of cortical thickness using magnetic resonance imaging was performed on a large cohort of 918 relapsing-remitting multiple sclerosis patients who participated in a phase III multicenter clinical trial. An automatic lesion in-painting algorithm was developed and implemented. Cortical thickness was measured using the FreeSurfer pipeline with and without in-painting. The effect of in-painting was evaluated using FreeSurfer's paired analysis pipeline. Multivariate regression analysis was also performed with field strength and lesion load as additional factors. Overall, the estimated cortical thickness was different with in-painting than without. The effect of in-painting was observed to be region dependent, more significant in the left hemisphere compared to the right, was more prominent at 1.5 T relative to 3 T, and was greater at higher lesion volumes. Our results show that even for data acquired at 1.5 T in patients with high lesion load, the mean cortical thickness difference with and without in-painting is ∼2%. Based on these results, it appears that in-painting has only a small effect on the estimated regional and global cortical thickness. Hum Brain Mapp 36:3749-3760, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

SPE-IMS-MS: An automated platform for sub-sixty second surveillance of endogenous metabolites and xenobiotics in biofluids

PubMed Central

Zhang, Xing; Romm, Michelle; Zheng, Xueyun; Zink, Erika M.; Kim, Young-Mo; Burnum-Johnson, Kristin E.; Orton, Daniel J.; Apffel, Alex; Ibrahim, Yehia M.; Monroe, Matthew E.; Moore, Ronald J.; Smith, Jordan N.; Ma, Jian; Renslow, Ryan S.; Thomas, Dennis G.; Blackwell, Anne E.; Swinford, Glenn; Sausen, John; Kurulugama, Ruwan T.; Eno, Nathan; Darland, Ed; Stafford, George; Fjeldsted, John; Metz, Thomas O.; Teeguarden, Justin G.; Smith, Richard D.; Baker, Erin S.

2017-01-01

Characterization of endogenous metabolites and xenobiotics is essential to deconvoluting the genetic and environmental causes of disease. However, surveillance of chemical exposure and disease-related changes in large cohorts requires an analytical platform that offers rapid measurement, high sensitivity, efficient separation, broad dynamic range, and application to an expansive chemical space. Here, we present a novel platform for small molecule analyses that addresses these requirements by combining solid-phase extraction with ion mobility spectrometry and mass spectrometry (SPE-IMS-MS). This platform is capable of performing both targeted and global measurements of endogenous metabolites and xenobiotics in human biofluids with high reproducibility (CV 6 3%), sensitivity (LODs in the pM range in biofluids) and throughput (10-s sample-to-sample duty cycle). We report application of this platform to the analysis of human urine from patients with and without type 1 diabetes, where we observed statistically significant variations in the concentration of disaccharides and previously unreported chemical isomers. This SPE-IMS-MS platform overcomes many of the current challenges of large-scale metabolomic and exposomic analyses and offers a viable option for population and patient cohort screening in an effort to gain insights into disease processes and human environmental chemical exposure. PMID:29276770

Simulated in vivo Electrophysiology Experiments Provide Previously Inaccessible Insights into Visual Physiology

PubMed Central

Quiroga, Maria del Mar; Price, Nicholas SC

2016-01-01

Lecture content and practical laboratory classes are ideally complementary. However, the types of experiments that have led to our detailed understanding of sensory neuroscience are often not amenable to classroom experimentation as they require expensive equipment, time-consuming surgeries, specialized experimental techniques, and the use of animals. While sometimes feasible in small group teaching, these experiments are not suitable for large cohorts of students. Previous attempts to expose students to sensory neuroscience experiments include: the use of electrophysiology preparations in invertebrates, data-driven simulations that do not replicate the experience of conducting an experiment, or simply observing an experiment in a research laboratory. We developed an online simulation of a visual neuroscience experiment in which extracellular recordings are made from a motion sensitive neuron. Students have control over stimulation parameters (direction and contrast) and can see and hear the action potential responses to stimuli as they are presented. The simulation provides an intuitive way for students to gain insight into neurophysiology, including experimental design, data collection and data analysis. Our simulation allows large cohorts of students to cost-effectively “experience” the results of animal research without ethical concerns, to be exposed to realistic data variability, and to develop their understanding of how sensory neuroscience experiments are conducted. PMID:27980465

Machine learning for neuroimaging with scikit-learn.

PubMed

Abraham, Alexandre; Pedregosa, Fabian; Eickenberg, Michael; Gervais, Philippe; Mueller, Andreas; Kossaifi, Jean; Gramfort, Alexandre; Thirion, Bertrand; Varoquaux, Gaël

2014-01-01

Statistical machine learning methods are increasingly used for neuroimaging data analysis. Their main virtue is their ability to model high-dimensional datasets, e.g., multivariate analysis of activation images or resting-state time series. Supervised learning is typically used in decoding or encoding settings to relate brain images to behavioral or clinical observations, while unsupervised learning can uncover hidden structures in sets of images (e.g., resting state functional MRI) or find sub-populations in large cohorts. By considering different functional neuroimaging applications, we illustrate how scikit-learn, a Python machine learning library, can be used to perform some key analysis steps. Scikit-learn contains a very large set of statistical learning algorithms, both supervised and unsupervised, and its application to neuroimaging data provides a versatile tool to study the brain.

Machine learning for neuroimaging with scikit-learn

PubMed Central

Abraham, Alexandre; Pedregosa, Fabian; Eickenberg, Michael; Gervais, Philippe; Mueller, Andreas; Kossaifi, Jean; Gramfort, Alexandre; Thirion, Bertrand; Varoquaux, Gaël

2014-01-01

Statistical machine learning methods are increasingly used for neuroimaging data analysis. Their main virtue is their ability to model high-dimensional datasets, e.g., multivariate analysis of activation images or resting-state time series. Supervised learning is typically used in decoding or encoding settings to relate brain images to behavioral or clinical observations, while unsupervised learning can uncover hidden structures in sets of images (e.g., resting state functional MRI) or find sub-populations in large cohorts. By considering different functional neuroimaging applications, we illustrate how scikit-learn, a Python machine learning library, can be used to perform some key analysis steps. Scikit-learn contains a very large set of statistical learning algorithms, both supervised and unsupervised, and its application to neuroimaging data provides a versatile tool to study the brain. PMID:24600388

A review of approaches to identifying patient phenotype cohorts using electronic health records

PubMed Central

Shivade, Chaitanya; Raghavan, Preethi; Fosler-Lussier, Eric; Embi, Peter J; Elhadad, Noemie; Johnson, Stephen B; Lai, Albert M

2014-01-01

Objective To summarize literature describing approaches aimed at automatically identifying patients with a common phenotype. Materials and methods We performed a review of studies describing systems or reporting techniques developed for identifying cohorts of patients with specific phenotypes. Every full text article published in (1) Journal of American Medical Informatics Association, (2) Journal of Biomedical Informatics, (3) Proceedings of the Annual American Medical Informatics Association Symposium, and (4) Proceedings of Clinical Research Informatics Conference within the past 3 years was assessed for inclusion in the review. Only articles using automated techniques were included. Results Ninety-seven articles met our inclusion criteria. Forty-six used natural language processing (NLP)-based techniques, 24 described rule-based systems, 41 used statistical analyses, data mining, or machine learning techniques, while 22 described hybrid systems. Nine articles described the architecture of large-scale systems developed for determining cohort eligibility of patients. Discussion We observe that there is a rise in the number of studies associated with cohort identification using electronic medical records. Statistical analyses or machine learning, followed by NLP techniques, are gaining popularity over the years in comparison with rule-based systems. Conclusions There are a variety of approaches for classifying patients into a particular phenotype. Different techniques and data sources are used, and good performance is reported on datasets at respective institutions. However, no system makes comprehensive use of electronic medical records addressing all of their known weaknesses. PMID:24201027

Association of Discoid Lupus with Clinical Manifestations and Damage Accrual in PROFILE: A Multiethnic Lupus Cohort

PubMed Central

Santiago-Casas, Yesenia; Vilá, Luis M.; McGwin, Gerald; Cantor, Ryan S.; Petri, Michelle; Ramsey-Goldman, Rosalind; Reveille, John D.; Kimberly, Robert P.; Alarcón, Graciela S.; Brown, Elizabeth E.

2013-01-01

Objective To determine the clinical manifestations and disease damage associated with discoid rash in a large multiethnic systemic lupus erythematosus (SLE) cohort. Methods SLE patients (per ACR criteria), age ≥ 16 years, disease duration ≤ 10 years at enrollment, and defined ethnicity (African American, Hispanic or Caucasian), from a longitudinal cohort were studied. Socioeconomic-demographic features, clinical manifestations and disease damage [as per the Systemic Lupus International Collaborating Clinics Damage Index (SDI)] were determined. The association of DLE with clinical manifestations and disease damage was examined using multivariable logistic regression. Results A total of 2,228 SLE patients were studied. The mean (standard deviation, SD) age at diagnosis was 34.3 (12.8) years and the mean (SD) disease duration was 7.9 (6.0) years; 91.8% were women. Discoid lupus was observed in 393 (17.6%) of patients with SLE. In the multivariable analysis, patients with discoid lupus were more likely to be smokers and of African-American ethnicity, and to have malar rash, photosensitivity, oral ulcers, leukopenia and vasculitis. DLE patients were less likely to be of Hispanic (from Texas) ethnicity, and to have arthritis, end-stage renal disease (ESRD), and antinuclear, anti-dsDNA and anti-phospholipid antibodies. Patients with DLE had more damage accrual, particularly chronic seizures, scarring alopecia, scarring of the skin, and skin ulcers. Conclusion In this cohort of SLE patients, discoid lupus was associated with several clinical features including serious manifestations such as vasculitis and chronic seizures. PMID:22190480

Study Protocol, Sample Characteristics, and Loss to Follow-Up: The OPPERA Prospective Cohort Study

PubMed Central

Bair, Eric; Brownstein, Naomi C.; Ohrbach, Richard; Greenspan, Joel D.; Dubner, Ron; Fillingim, Roger B.; Maixner, William; Smith, Shad; Diatchenko, Luda; Gonzalez, Yoly; Gordon, Sharon; Lim, Pei-Feng; Ribeiro-Dasilva, Margarete; Dampier, Dawn; Knott, Charles; Slade, Gary D.

2013-01-01

When studying incidence of pain conditions such as temporomandibular disorders (TMDs), repeated monitoring is needed in prospective cohort studies. However, monitoring methods usually have limitations and, over a period of years, some loss to follow-up is inevitable. The OPPERA prospective cohort study of first-onset TMD screened for symptoms using quarterly questionnaires and examined symptomatic participants to definitively ascertain TMD incidence. During the median 2.8-year observation period, 16% of the 3,263 enrollees completed no follow-up questionnaires, others provided incomplete follow-up, and examinations were not conducted for one third of symptomatic episodes. Although screening methods and examinations were found to have excellent reliability and validity, they were not perfect. Loss to follow-up varied according to some putative TMD risk factors, although multiple imputation to correct the problem suggested that bias was minimal. A second method of multiple imputation that evaluated bias associated with omitted and dubious examinations revealed a slight underestimate of incidence and some small biases in hazard ratios used to quantify effects of risk factors. Although “bottom line” statistical conclusions were not affected, multiply-imputed estimates should be considered when evaluating the large number of risk factors under investigation in the OPPERA study. Perspective These findings support the validity of the OPPERA prospective cohort study for the purpose of investigating the etiology of first-onset TMD, providing the foundation for other papers investigating risk factors hypothesized in the OPPERA project. PMID:24275220

The Effect of Intensive Glycemic Treatment on Coronary Artery Calcification in Type 1 Diabetic Participants of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

PubMed Central

Cleary, Patricia A.; Orchard, Trevor J.; Genuth, Saul; Wong, Nathan D.; Detrano, Robert; Backlund, Jye-Yu C.; Zinman, Bernard; Jacobson, Alan; Sun, Wanjie; Lachin, John M.; Nathan, David M.

2008-01-01

The Epidemiology of Diabetes Interventions and Complications (EDIC) study, an observational follow-up of the Diabetes Control and Complications Trial (DCCT) type 1 diabetes cohort, measured coronary artery calcification (CAC), an index of atherosclerosis, with computed tomography (CT) in 1,205 EDIC patients at ~7–9 years after the end of the DCCT. We examined the influence of the 6.5 years of prior conventional versus intensive diabetes treatment during the DCCT, as well as the effects of cardiovascular disease risk factors, on CAC. The prevalences of CAC >0 and >200 Agatston units were 31.0 and 8.5%, respectively. Compared with the conventional treatment group, the intensive group had significantly lower geometric mean CAC scores and a lower prevalence of CAC >0 in the primary retinopathy prevention cohort, but not in the secondary intervention cohort, and a lower prevalence of CAC >200 in the combined cohorts. Waist-to-hip ratio, smoking, hypertension, and hypercholesterolemia, before or at the time of CT, were significantly associated with CAC in univariate and multivariate analyses. CAC was associated with mean HbA1c (A1C) levels before enrollment, during the DCCT, and during the EDIC study. Prior intensive diabetes treatment during the DCCT was associated with less atherosclerosis, largely because of reduced levels of A1C during the DCCT. PMID:17130504

Maternal and offspring outcomes in women with intellectual and developmental disabilities: a population-based cohort study.

PubMed

Brown, H K; Cobigo, V; Lunsky, Y; Vigod, S N

2017-04-01

To compare the risks for adverse maternal and offspring outcomes in women with and without intellectual and developmental disabilities. Population-based cohort study. Ontario, Canada. Singleton obstetrical deliveries to 18- to 49-year-old women with and without intellectual and developmental disabilities (n = 3932 in the exposed cohort, n = 382 774 in the unexposed cohort; 2002-2011 fiscal years). Women with intellectual and developmental disabilities were identified based on diagnoses in health administrative data or receipt of disability income support. The unexposed cohort comprised women without intellectual and developmental disabilities. Modified Poisson regression was used to compute adjusted relative risks (aRR) and 95% confidence intervals (CI) comparing the two cohorts. Primary maternal outcomes were: gestational diabetes, gestational hypertension, pre-eclampsia, eclampsia, and venous thromboembolism. Primary offspring outcomes were: preterm birth, small for gestational age, and large for gestational age. The exposed cohort, compared with the unexposed cohort, had increased risks for pre-eclampsia (aRR 1.47, 95% CI 1.11-1.93) and venous thromboembolism (aRR 1.60, 95% CI 1.17-2.19). Their offspring had increased risks for preterm birth (aRR 1.63, 95% CI 1.47-1.80) and small for gestational age (aRR 1.35, 95% CI 1.25-1.45). These findings suggest that there is a need to address modifiable risk factors for adverse outcomes among women with intellectual and developmental disabilities prior to and during pregnancy. Moreover, there is a need to enhance monitoring for maternal and offspring complications in this population. Large cohort study: intellectual and developmental disabilities predispose women/babies to adverse outcomes. © 2016 Royal College of Obstetricians and Gynaecologists.

External validation of a risk assessment model for venous thromboembolism in the hospitalised acutely-ill medical patient (VTE-VALOURR).

PubMed

Mahan, Charles E; Liu, Yang; Turpie, A Graham; Vu, Jennifer T; Heddle, Nancy; Cook, Richard J; Dairkee, Undaleeb; Spyropoulos, Alex C

2014-10-01

Venous thromboembolic (VTE) risk assessment remains an important issue in hospitalised, acutely-ill medical patients, and several VTE risk assessment models (RAM) have been proposed. The purpose of this large retrospective cohort study was to externally validate the IMPROVE RAM using a large database of three acute care hospitals. We studied 41,486 hospitalisations (28,744 unique patients) with 1,240 VTE hospitalisations (1,135 unique patients) in the VTE cohort and 40,246 VTE-free hospitalisations (27,609 unique patients) in the control cohort. After chart review, 139 unique VTE patients were identified and 278 randomly-selected matched patients in the control cohort. Seven independent VTE risk factors as part of the RAM in the derivation cohort were identified. In the validation cohort, the incidence of VTE was 0.20%; 95% confidence interval (CI) 0.18-0.22, 1.04%; 95%CI 0.88-1.25, and 4.15%; 95%CI 2.79-8.12 in the low, moderate, and high VTE risk groups, respectively, which compared to rates of 0.45%, 1.3%, and 4.74% in the three risk categories of the derivation cohort. For the derivation and validation cohorts, the total percentage of patients in low, moderate and high VTE risk occurred in 68.6% vs 63.3%, 24.8% vs 31.1%, and 6.5% vs 5.5%, respectively. Overall, the area under the receiver-operator characteristics curve for the validation cohort was 0.7731. In conclusion, the IMPROVE RAM can accurately identify medical patients at low, moderate, and high VTE risk. This will tailor future thromboprophylactic strategies in this population as well as identify particularly high VTE risk patients in whom multimodal or more intensive prophylaxis may be beneficial.

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.

A patient cohort on long-term sequelae of sepsis survivors: study protocol of the Mid-German Sepsis Cohort.

PubMed

Scherag, André; Hartog, Christiane S; Fleischmann, Carolin; Ouart, Dominique; Hoffmann, Franziska; König, Christian; Kesselmeier, Miriam; Fiedler, Sandra; Philipp, Monique; Braune, Anke; Eichhorn, Cornelia; Gampe, Christin; Romeike, Heike; Reinhart, Konrad

2017-08-23

An increasing number of patients survive sepsis; however, we lack valid data on the long-term impact on morbidity from prospective observational studies. Therefore, we designed an observational cohort to quantify mid-term and long-term functional disabilities after intensive care unit (ICU)-treated sepsis. Ultimately, findings for the Mid-German Sepsis Cohort (MSC) will serve as basis for the implementation of follow-up structures for patients with sepsis and help to increase quality of care for sepsis survivors. All patients surviving ICU-treated sepsis are eligible and are recruited from five study centres in Germany (acute care hospital setting in Jena, Halle/Saale, Leipzig, Bad Berka, Erfurt; large long-term acute care hospital and rehabilitation setting in Klinik Bavaria Kreischa). Screening is performed by trained study nurses. Data are collected on ICU management of sepsis. On written informed consent provided by patients or proxies, follow-up is carried out by trained research staff at 3, 6 and 12 months and yearly thereafter. The primary outcome is functional disability as assessed by (instrumental) activities of daily living. Other outcomes cover domains like mortality, cognitive, emotional and physical impairment, and resource use. The estimated sample size of 3000 ICU survivors is calculated to allow detection of relevant changes in the primary outcome in sepsis survivors longitudinally. The study is conducted according to the current version of the Declaration of Helsinki and has been approved by four local/federal responsible institutional ethics committees and by the respective federal data protection commissioners. Results of MSC will be fed back to the patients and published in peer-reviewed journals. German Clinical Trials Registry DRKS00010050. © 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.

Rationale and design of three observational, prospective cohort studies including biobanking to evaluate and improve diagnostics, management strategies and risk stratification in venous thromboembolism: the VTEval Project

PubMed Central

Frank, Bernd; Ariza, Liana; Lamparter, Heidrun; Grossmann, Vera; Prochaska, Jürgen H; Ullmann, Alexander; Kindler, Florentina; Weisser, Gerhard; Walter, Ulrich; Lackner, Karl J; Espinola-Klein, Christine; Münzel, Thomas; Konstantinides, Stavros V; Wild, Philipp S

2015-01-01

Introduction Venous thromboembolism (VTE) with its two manifestations deep vein thrombosis (DVT) and pulmonary embolism (PE) is a major public health problem. The VTEval Project aims to investigate numerous research questions on diagnosis, clinical management, treatment and prognosis of VTE, which have remained uncertain to date. Methods and analysis The VTEval Project consists of three observational, prospective cohort studies on VTE comprising cohorts of individuals with a clinical suspicion of acute PE (with or without DVT), with a clinical suspicion of acute DVT (without symptomatic PE) and with an incidental diagnosis of VTE (PE or DVT). The VTEval Project expects to enrol a total of approximately 2000 individuals with subsequent active and passive follow-up investigations over a time period of 5 years per participant. Time points for active follow-up investigations are at months 3, 6, 12, 24 and 36 after diagnosis (depending on the disease cohort); passive follow-up investigations via registry offices and the cancer registry are performed 48 and 60 months after diagnosis for all participants. Primary short-term outcome is defined by overall mortality (PE-related death and all other causes of death), primary long-term outcome by symptomatic VTE (PE-related death, recurrence of non-fatal PE or DVT). The VTEval Project includes three ‘all-comer’ studies and involves the standardised acquisition of high-quality data, covering the systematic assessment of VTE including symptoms, risk profile, psychosocial, environmental and lifestyle factors as well as clinical and subclinical disease, and it builds up a large state-of-the-art biorepository containing various materials from serial blood samplings. Ethics and dissemination The VTEval Project has been approved by the local data safety commissioner and the responsible ethics committee (reference no. 837.320.12 (8421-F)). Trial results will be published in peer-reviewed journals and presented at national and international scientific meetings. Trial registration number NCT02156401. PMID:26133379

Dairy products and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition.

PubMed

Duarte-Salles, Talita; Fedirko, Veronika; Stepien, Magdalena; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Lukanova, Annekatrin; Trepo, Elisabeth; Overvad, Kim; Tjønneland, Anne; Halkjaer, Jytte; Boutron-Ruault, Marie-Christine; Racine, Antoine; Cadeau, Claire; Kühn, Tilman; Aleksandrova, Krasimira; Trichopoulos, Dimitrios; Tsiotas, Konstantinos; Boffetta, Paolo; Palli, Domenico; Pala, Valeria; Tumino, Rosario; Sacerdote, Carlotta; Panico, Salvatore; Bueno-de-Mesquita, H B as; Dik, Vincent K; Peeters, Petra H; Weiderpass, Elisabete; Torhild Gram, Inger; Hjartåker, Anette; Ramón Quirós, Jose; Fonseca-Nunes, Ana; Molina-Montes, Esther; Dorronsoro, Miren; Navarro Sanchez, Carmen; Barricarte, Aurelio; Lindkvist, Björn; Sonestedt, Emily; Johansson, Ingegerd; Wennberg, Maria; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth C; Romieu, Isabelle; Riboli, Elio; Jenab, Mazda

2014-10-01

Intake of dairy products has been associated with risk of some cancers, but findings are often inconsistent and information on hepatocellular carcinoma (HCC) risk is limited, particularly from prospective settings. The aim of our study was to investigate the association between consumption of total and specific dairy products (milk/cheese/yogurt) and their components (calcium/vitamin D/fats/protein), with first incident HCC (N(cases) = 191) in the European Prospective Investigation into Cancer and Nutrition cohort, including a nested case-control subset (N(cases) = 122) with the assessment of hepatitis B virus/hepatitis C virus infections status, liver damage and circulating insulin-like growth factor (IGF)-I levels. For cohort analyses, multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI). For nested case-control analyses, conditional logistic regression was used to calculate odds ratios and 95% CI. A total of 477,206 participants were followed-up for an average of 11 years (person-years follow-up = 5,415,385). In the cohort study, a significant positive HCC risk association was observed for total dairy products (highest vs. lowest tertile, HR = 1.66, 95% CI: 1.13-2.43; p(trend) = 0.012), milk (HR = 1.51, 95% CI: 1.02-2.24; p(trend) = 0.049), and cheese (HR = 1.56, 95% CI: 1.02-2.38; p(trend) = 0.101), but not yogurt (HR = 0.94, 95% CI: 0.65-1.35). Dietary calcium, vitamin D, fat and protein from dairy sources were associated with increased HCC risk, whereas the same nutrients from nondairy sources showed inverse or null associations. In the nested case-control study, similar results were observed among hepatitis-free individuals. Results from this large prospective cohort study suggest that higher consumption of dairy products, particularly milk and cheese, may be associated with increased HCC risk. Validation of these findings in other populations is necessary. Potential biologic mechanisms require further exploration. © 2014 UICC.

Pregnancy as a Window to Future Cardiovascular Health: Design and Implementation of the nuMoM2b Heart Health Study.

PubMed

Haas, David M; Ehrenthal, Deborah B; Koch, Matthew A; Catov, Janet M; Barnes, Shannon E; Facco, Francesca; Parker, Corette B; Mercer, Brian M; Bairey-Merz, C Noel; Silver, Robert M; Wapner, Ronald J; Simhan, Hyagriv N; Hoffman, Matthew K; Grobman, William A; Greenland, Philip; Wing, Deborah A; Saade, George R; Parry, Samuel; Zee, Phyllis C; Reddy, Uma M; Pemberton, Victoria L; Burwen, Dale R

2016-03-15

The National Institute of Child Health and Human Development's Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study (HHS) was designed to investigate the relationships between adverse pregnancy outcomes and modifiable risk factors for cardiovascular disease. The ongoing nuMoM2b-HHS, which started in 2013, is a prospective follow-up of the nuMoM2b cohort, which included 10,038 women recruited between 2010 and 2013 from 8 centers across the United States who were initially observed over the course of their first pregnancies. In this report, we detail the design and study procedures of the nuMoM2b-HHS. Women in the pregnancy cohort who consented to be contacted for participation in future studies were approached at 6-month intervals to ascertain health information and to maintain ongoing contact. Two to 5 years after completion of the pregnancy documented in the nuMoM2b, women in the nuMoM2b-HHS were invited to an in-person study visit. During this visit, they completed psychosocial and medical history questionnaires and had clinical measurements and biological specimens obtained. A subcohort of participants who had objective assessments of sleep-disordered breathing during pregnancy were asked to repeat this investigation. This unique prospective observational study includes a large, geographically and ethnically diverse cohort, rich depth of phenotypic information about adverse pregnancy outcomes, and clinical data and biospecimens from early in the index pregnancy onward. Data obtained from this cohort will provide mechanistic and clinical insights into how data on a first pregnancy can provide information about the potential development of subsequent risk factors for cardiovascular disease. © The Author 2016. 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.

Apneic oxygenation reduces hypoxemia during endotracheal intubation in the pediatric emergency department.

PubMed

Vukovic, Adam A; Hanson, Holly R; Murphy, Shelley L; Mercurio, Danielle; Sheedy, Craig A; Arnold, Donald H

2018-04-18

Apneic oxygenation (AO) has been evaluated in adult patients as a means of reducing hypoxemia during endotracheal intubation (ETI). While less studied in pediatric patients, its practice has been largely adopted. Determine association between AO and hypoxemia in pediatric patients undergoing ETI. Observational study at an urban, tertiary children's hospital emergency department. Pediatric patients undergoing ETI were examined during eras without (January 2011-June 2011) and with (August 2014-March 2017) apneic oxygenation. The primary outcome was hypoxemia, defined as pulse oximetry (SpO 2 ) < 90%. The χ 2 and Wilcoxon rank-sum tests examined differences between cohorts. Multivariable regression models examined adjusted associations between covariates and hypoxemia. 149 patients were included. Cohorts were similar except for greater incidence of altered mental status in those receiving AO (26% vs. 7%, p = 0.03). Nearly 50% of the pre-AO cohort experienced hypoxemia during ETI, versus <25% in the AO cohort. Median [IQR] lowest SpO 2 during ETI was 93 (69, 99) for pre-AO and 100 [95, 100] for the AO cohort (p < 0.001). In a multivariable logistic regression model, hypoxemia during ETI was associated with AO (aOR 0.3, 95% confidence interval [CI] 0.1-0.8), increased age (for 1 year, aOR 0.8, 95% CI 0.7-1.0), lowest SpO 2 before ETI (for 1% increase, aOR 0.9, 95% CI 0.8-1.0), and each additional intubation attempt (aOR 4.0, 95% CI 2.2-7.2). Apneic oxygenation is an easily-applied intervention associated with decreases in hypoxemia during pediatric ETI. Nearly 50% of children not receiving AO experienced hypoxemia. Copyright © 2018 Elsevier Inc. All rights reserved.

Smoking and elevated blood pressure are the most important risk factors for subarachnoid hemorrhage in the Asia-Pacific region: an overview of 26 cohorts involving 306,620 participants.

PubMed

Feigin, Valery; Parag, Varsha; Lawes, Carlene M M; Rodgers, Anthony; Suh, Il; Woodward, Mark; Jamrozik, Konrad; Ueshima, Hirotsugu

2005-07-01

The cause of subarachnoid hemorrhage (SAH) is poorly understood and there are few large cohort studies of risk factors for SAH. We investigated the risk of SAH mortality and morbidity associated with common cardiovascular risk factors in the Asia-Pacific region and examined whether the strengths of these associations were different in Asian and Australasian (predominantly white) populations. Cohort studies were identified from Internet electronic databases, searches of proceedings of meetings, and personal communication. Hazard ratios (HRs) for systolic blood pressure (SBP), current smoking, total serum cholesterol, body mass index (BMI), and alcohol drinking were calculated from Cox models that were stratified by sex and cohort and adjusted for age at risk. Individual participant data from 26 prospective cohort studies (total number of participants 306,620) that reported incident cases of SAH (fatal and/or nonfatal) were available for analysis. During the median follow-up period of 8.2 years, a total of 236 incident cases of SAH were observed. Current smoking (HR, 2.4; 95% CI, 1.8 to 3.4) and SBP >140 mm Hg (HR, 2.0; 95% CI, 1.5 to 2.7) were significant and independent risk factors for SAH. Attributable risks of SAH associated with current smoking and elevated SBP (> or =140 mm Hg) were 29% and 19%, respectively. There were no significant associations between the risk of SAH and cholesterol, BMI, or drinking alcohol. The strength of the associations of the common cardiovascular risk factors with the risk of SAH did not differ much between Asian and Australasian regions. Cigarette smoking and SBP are the most important risk factors for SAH in the Asia-Pacific region.

A nationwide population-based retrospective cohort study of the risk of uterine, ovarian and breast cancer in women with polycystic ovary syndrome.

PubMed

Shen, Cheng-Che; Yang, Albert C; Hung, Jeng-Hsiu; Hu, Li-Yu; Tsai, Shih-Jen

2015-01-01

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. We used a nationwide population-based retrospective cohort study to explore the relationship between PCOS and the subsequent development of gynecological cancers including uterine, breast, or ovarian cancer. We identified subjects who were diagnosed with PCOS between January 1, 2000, and December 31, 2004, in the Taiwan National Health Insurance (NHI) Research Database. A comparison cohort was constructed for patients without known PCOS who were also matched according to age. All PCOS and control patients were observed until diagnosed with breast cancer, ovarian cancer, or uterine cancer or until death, withdrawal from the NHI system, or December 31, 2009. The PCOS cohort consisted of 3,566 patients, and the comparison cohort consisted of 14,264 matched control patients without PCOS. The adjusted hazard ratio (HR) of uterine cancer and breast cancer in subjects with PCOS were higher (HR: 8.42 [95% confidence interval: 1.62-43.89] and HR: 1.99 [95% confidence interval: 1.05-3.77], respectively) than that of the controls during the follow-up. With the Monte Carlo method, only the mean adjusted HR of 1,000 comparisons for developing uterine cancer during the follow-up period was greater for the PCOS group than for the control groups (HR: 4.71, 95% confidence interval: 1.57-14.11). PCOS might increase the risk of subsequent newly diagnosed uterine cancer. It is critical that further large-scale, well-designed studies be conducted to confirm the association between PCOS and gynecological cancer risk. ©AlphaMed Press.

Disease Course and Colectomy Rate of Ulcerative Colitis: A Follow-up Cohort Study of a Referral Center in Tuscany.

PubMed

Manetti, Natalia; Bagnoli, Siro; Rogai, Francesca; Bonanomi, Andrea G; Vannozzi, Giancarlo; Giannotta, Martina; Annese, Vito

2016-08-01

The disease course and colectomy rate of ulcerative colitis (UC) vary largely in population-based and referral center cohorts. We retrospectively evaluated our cohort to determine the disease course and risk factors for colectomy. A cohort of 1723 ulcerative colitis patients (986 males; mean age, 34.8 ± 15.4 yrs) were identified and followed since 1960s for a mean of 11 ± 9 years (range, 1-49 yrs). The disease extension was classified as E1, E2, and E3 on diagnosis at 19.7%, 54.2%, and 26.1% of patients, respectively. At the final follow-up, the disease extension increased in 20% of the cases. Extraintestinal manifestations (EIMs) were reported by 11% of the patients, whereas systemic corticosteroids (CS), IM or anti-TNFα agents were used by 68.6%, 20.4%, and 6.4% of patients, respectively. The crude colectomy rate was 7% (120 pts), with a 1.2% rate (n = 21) at 1 year from diagnosis (95% CI, 0.7-1.7) and a Kaplan-Meyer estimation of up to 18.2% after 30 years of follow-up. The 1-year colectomy rate showed no significant difference through the decades, whereas the 5-year and 10-year absolute value of colectomy was halved in the last 2 decades compared with the period from 1960 to 1990 (P = 0.01), with a general trend of a reduced colectomy rate at survival curves (P = 0.056). The colectomy rate was low in our cohort and further reduced in the last 2 decades. However, despite the availability of anti-TNFα agents, no further significant reduction of colectomies was observed in the last decade.

NSAIDs utilization for musculoskeletal indications in elderly patients with cerebro/cardiovascular disease.

PubMed

Roberto, Giuseppe; Bartolini, Claudia; Rea, Federico; Onder, Graziano; Vitale, Cristiana; Trifirò, Gianluca; Kirchmayer, Ursula; Chinellato, Alessandro; Lucenteforte, Ersilia; Corrao, Giovanni; Mugelli, Alessandro; Lapi, Francesco; Gini, Rosa

2018-05-01

To describe NSAID utilization for musculoskeletal conditions in a large cohort of Italian elderly with cerebro/cardiovascular disease, a population in which NSAIDs should be generally avoided due to the prothrombotic potential. Administrative data from five Italian geographic areas were analyzed. Patients aged ≥ 65 with a cerebro/cardiovascular event recorded between 2008 and 2011 (cohort entry) were selected. Prescription NSAIDs reimbursed for musculoskeletal conditions and dispensed during 1 year follow-up were retrieved to describe (i) prevalence of use, (ii) average amount of defined daily doses of NSAIDs claimed by users per day of follow-up, and (iii) distribution of the received daily dose (RDD) among patients with ≥ 2 dispensings. Among new users, i.e., patients without NSAID dispensings during 2 years before cohort entry, the first dispensed NSAID molecule was observed. Overall, 511,989 patients were selected. Across the five geographic areas, prevalence of use ranged from 48 to 21% and average consumption ranged between 30 and 67 DDD/1000 users/day. Around 10% of patients in the overall cohort had a RDD > 1. Nimesulide (9.6%) and diclofenac (7.5%) had the highest prevalence of use. The most consumed NSAIDs were nimesulide and coxibs with 10.6 and 7.5 DDD/1000 users/day, respectively. Among new users recruited in 2011, 30% had diclofenac or a coxibs as the first prescription. NSAID use was common in the study cohort, particularly in central-southern areas. In contrast with current recommendations, coxibs and diclofenac were among the most prescribed active principles, even in new users. Interventions to promote appropriateness of use are warranted.

Demographics, clinical disease characteristics, and quality of life in a large cohort of psoriasis patients with and without psoriatic arthritis

PubMed Central

Truong, B; Rich-Garg, N; Ehst, BD; Deodhar, AA; Ku, JH; Vakil-Gilani, K; Danve, A; Blauvelt, A

2015-01-01

Innovation What is already known about the topic: psoriasis (PsO) is a common skin disease with major impact on quality of life (QoL). Patient-reported data on QoL from large number of PsO patients with and without psoriatic arthritis (PsA) are limited. What this study adds: In a large cohort referred to a university psoriasis center, patients with PsO and concomitant PsA (~30% in this group) had greater degrees of skin and nail involvement and experienced greater negative impacts on QoL. Despite large numbers of patients with moderate-to-severe disease, use of systemic therapy by community practitioners was uncommon. Background PsO and PsA are common diseases that have marked adverse impacts on QoL. The disease features and patient-reported QoL data comparing PsO and PsA patients are limited. Objective To identify and compare demographics, clinical disease characteristics, and QoL scores in a large cohort of PsO patients with and without PsA. Methods All PsO patients seen in a psoriasis specialty clinic, named the Center of Excellence for Psoriasis and Psoriatic Arthritis, were enrolled in an observational cohort. Demographic, QoL, and clinical data were collected from patient-reported questionnaires and from physical examinations performed by Center of Excellence for Psoriasis and Psoriatic Arthritis dermatologists and a rheumatologists. Cross sectional descriptive data were collected and comparisons between patients with PsO alone and those with concomitant PsA are presented. Results A total of 568 patients were enrolled in the database. Mean age of PsO onset was 28 years and mean disease duration was 18 years. Those with family history had an earlier onset of PsO by ~7 years. Mean body surface area involvement with PsO was 14%. Mean body mass index was 30.7. Prevalence of PsA was 29.8%. PsA patients had a higher mean body surface area compared to patients with PsO alone (16.7% vs 13.4%, P<0.05), higher prevalence of psoriatic nail changes (54.4% vs 36%, P<0.0002), and worse QoL scores as assessed by the Short Form-12 (67 vs 52, P<0.00001), Psoriasis Quality of Life-12 questionnaire (62 vs 71, P<0.01), and Routine Assessment of Patient Index Data 3 (2.3 vs 4.7, P<0.01). Strikingly, 49% of patients with PsO had never received any systemic therapy. Conclusion These data highlight that PsO has marked negative impacts on QoL, while those patients with concomitant PsA are affected to a much greater degree. Despite large numbers of patients presenting with moderate-to-severe disease, use of systemic therapy for both PsO and PsA was uncommon. PMID:26622188

Carpal tunnel syndrome and computer exposure at work in two large complementary cohorts.

PubMed

Mediouni, Z; Bodin, J; Dale, A M; Herquelot, E; Carton, M; Leclerc, A; Fouquet, N; Dumontier, C; Roquelaure, Y; Evanoff, B A; Descatha, A

2015-09-09

The boom in computer use and concurrent high rates in musculoskeletal complaints and carpal tunnel syndrome (CTS) among users have led to a controversy about a possible link. Most studies have used cross-sectional designs and shown no association. The present study used longitudinal data from two large complementary cohorts to evaluate a possible relationship between CTS and the performance of computer work. The Cosali cohort is a representative sample of a French working population that evaluated CTS using standardised clinical examinations and assessed self-reported computer use. The PrediCTS cohort study enrolled newly hired clerical, service and construction workers in several industries in the USA, evaluated CTS using symptoms and nerve conduction studies (NCS), and estimated exposures to computer work using a job exposure matrix. During a follow-up of 3-5 years, the association between new cases of CTS and computer work was calculated using logistic regression models adjusting for sex, age, obesity and relevant associated disorders. In the Cosali study, 1551 workers (41.8%) completed follow-up physical examinations; 36 (2.3%) participants were diagnosed with CTS. In the PrediCTS study, 711 workers (64.2%) completed follow-up evaluations, whereas 31 (4.3%) had new cases of CTS. The adjusted OR for the group with the highest exposure to computer use was 0.39 (0.17; 0.89) in the Cosali cohort and 0.16 (0.05; 0.59) in the PrediCTS cohort. Data from two large cohorts in two different countries showed no association between computer work and new cases of CTS among workers in diverse jobs with varying job exposures. CTS is far more common among workers in non-computer related jobs; prevention efforts and work-related compensation programmes should focus on workers performing forceful hand exertion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Carpal tunnel syndrome and computer exposure at work in two large complementary cohorts

PubMed Central

Mediouni, Z; Bodin, J; Dale, A M; Herquelot, E; Carton, M; Leclerc, A; Fouquet, N; Dumontier, C; Roquelaure, Y; Evanoff, B A; Descatha, A

2015-01-01

Objectives The boom in computer use and concurrent high rates in musculoskeletal complaints and carpal tunnel syndrome (CTS) among users have led to a controversy about a possible link. Most studies have used cross-sectional designs and shown no association. The present study used longitudinal data from two large complementary cohorts to evaluate a possible relationship between CTS and the performance of computer work. Settings and participants The Cosali cohort is a representative sample of a French working population that evaluated CTS using standardised clinical examinations and assessed self-reported computer use. The PrediCTS cohort study enrolled newly hired clerical, service and construction workers in several industries in the USA, evaluated CTS using symptoms and nerve conduction studies (NCS), and estimated exposures to computer work using a job exposure matrix. Primary and secondary outcome measures During a follow-up of 3–5 years, the association between new cases of CTS and computer work was calculated using logistic regression models adjusting for sex, age, obesity and relevant associated disorders. Results In the Cosali study, 1551 workers (41.8%) completed follow-up physical examinations; 36 (2.3%) participants were diagnosed with CTS. In the PrediCTS study, 711 workers (64.2%) completed follow-up evaluations, whereas 31 (4.3%) had new cases of CTS. The adjusted OR for the group with the highest exposure to computer use was 0.39 (0.17; 0.89) in the Cosali cohort and 0.16 (0.05; 0.59) in the PrediCTS cohort. Conclusions Data from two large cohorts in two different countries showed no association between computer work and new cases of CTS among workers in diverse jobs with varying job exposures. CTS is far more common among workers in non-computer related jobs; prevention efforts and work-related compensation programmes should focus on workers performing forceful hand exertion. PMID:26353869

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.

Abdominal aortic aneurysm events in the women's health initiative: cohort study.

PubMed

Lederle, Frank A; Larson, Joseph C; Margolis, Karen L; Allison, Matthew A; Freiberg, Matthew S; Cochrane, Barbara B; Graettinger, William F; Curb, J David

2008-10-14

To assess the association between potential risk factors and subsequent clinically important abdominal aortic aneurysm events (repairs and ruptures) in women. Large prospective observational cohort study with mean follow-up of 7.8 years. 40 clinical centres across the United States. 161 808 postmenopausal women aged 50-79 enrolled in the women's health initiative. Association of self reported or measured baseline variables with confirmed abdominal aortic aneurysm events assessed with multiple logistic regression. Events occurred in 184 women and were strongly associated with age and smoking. Ever smoking, current smoking, and amount smoked all contributed independent risk. Diabetes showed a negative association (odds ratio 0.29, 95% confidence interval 0.13, 0.68), as did postmenopausal hormone therapy. Positive associations were also seen for height, hypertension, cholesterol lowering treatment, and coronary and peripheral artery disease. Our findings confirm the strong positive associations of clinically important abdominal aortic aneurysm with age and smoking in women and the negative association with diabetes previously reported in men.

Adjustment of Cell-Type Composition Minimizes Systematic Bias in Blood DNA Methylation Profiles Derived by DNA Collection Protocols

PubMed Central

Shiwa, Yuh; Hachiya, Tsuyoshi; Furukawa, Ryohei; Ohmomo, Hideki; Ono, Kanako; Kudo, Hisaaki; Hata, Jun; Hozawa, Atsushi; Iwasaki, Motoki; Matsuda, Koichi; Minegishi, Naoko; Satoh, Mamoru; Tanno, Kozo; Yamaji, Taiki; Wakai, Kenji; Hitomi, Jiro; Kiyohara, Yutaka; Kubo, Michiaki; Tanaka, Hideo; Tsugane, Shoichiro; Yamamoto, Masayuki; Sobue, Kenji; Shimizu, Atsushi

2016-01-01

Differences in DNA collection protocols may be a potential confounder in epigenome-wide association studies (EWAS) using a large number of blood specimens from multiple biobanks and/or cohorts. Here we show that pre-analytical procedures involved in DNA collection can induce systematic bias in the DNA methylation profiles of blood cells that can be adjusted by cell-type composition variables. In Experiment 1, whole blood from 16 volunteers was collected to examine the effect of a 24 h storage period at 4°C on DNA methylation profiles as measured using the Infinium HumanMethylation450 BeadChip array. Our statistical analysis showed that the P-value distribution of more than 450,000 CpG sites was similar to the theoretical distribution (in quantile-quantile plot, λ = 1.03) when comparing two control replicates, which was remarkably deviated from the theoretical distribution (λ = 1.50) when comparing control and storage conditions. We then considered cell-type composition as a possible cause of the observed bias in DNA methylation profiles and found that the bias associated with the cold storage condition was largely decreased (λadjusted = 1.14) by taking into account a cell-type composition variable. As such, we compared four respective sample collection protocols used in large-scale Japanese biobanks or cohorts as well as two control replicates. Systematic biases in DNA methylation profiles were observed between control and three of four protocols without adjustment of cell-type composition (λ = 1.12–1.45) and no remarkable biases were seen after adjusting for cell-type composition in all four protocols (λadjusted = 1.00–1.17). These results revealed important implications for comparing DNA methylation profiles between blood specimens from different sources and may lead to discovery of disease-associated DNA methylation markers and the development of DNA methylation profile-based predictive risk models. PMID:26799745

Small-for-gestational age and large-for-gestational age thresholds to predict infants at risk of adverse delivery and neonatal outcomes: are current charts adequate? An observational study from the Born in Bradford cohort

PubMed Central

Norris, T; Johnson, W; Farrar, D; Tuffnell, D; Wright, J; Cameron, N

2015-01-01

Objectives Construct an ethnic-specific chart and compare the prediction of adverse outcomes using this chart with the clinically recommended UK-WHO and customised birth weight charts using cut-offs for small-for-gestational age (SGA: birth weight <10th centile) and large-for-gestational age (LGA: birth weight >90th centile). Design Prospective cohort study. Setting Born in Bradford (BiB) study, UK. Participants 3980 White British and 4448 Pakistani infants with complete data for gestational age, birth weight, ethnicity, maternal height, weight and parity. Main outcome measures Prevalence of SGA and LGA, using the three charts and indicators of diagnostic utility (sensitivity, specificity and area under the receiver operating characteristic (AUROC)) of these chart-specific cut-offs to predict delivery and neonatal outcomes and a composite outcome. Results In White British and Pakistani infants, the prevalence of SGA and LGA differed depending on the chart used. Increased risk of SGA was observed when using the UK-WHO and customised charts as opposed to the ethnic-specific chart, while the opposite was apparent when classifying LGA infants. However, the predictive utility of all three charts to identify adverse clinical outcomes was poor, with only the prediction of shoulder dystocia achieving an AUROC>0.62 on all three charts. Conclusions Despite being recommended in national clinical guidelines, the UK-WHO and customised birth weight charts perform poorly at identifying infants at risk of adverse neonatal outcomes. Being small or large may increase the risk of an adverse outcome; however, size alone is not sensitive or specific enough with current detection to be useful. However, a significant amount of missing data for some of the outcomes may have limited the power needed to determine true associations. PMID:25783424

Adjustment of Cell-Type Composition Minimizes Systematic Bias in Blood DNA Methylation Profiles Derived by DNA Collection Protocols.

PubMed

Shiwa, Yuh; Hachiya, Tsuyoshi; Furukawa, Ryohei; Ohmomo, Hideki; Ono, Kanako; Kudo, Hisaaki; Hata, Jun; Hozawa, Atsushi; Iwasaki, Motoki; Matsuda, Koichi; Minegishi, Naoko; Satoh, Mamoru; Tanno, Kozo; Yamaji, Taiki; Wakai, Kenji; Hitomi, Jiro; Kiyohara, Yutaka; Kubo, Michiaki; Tanaka, Hideo; Tsugane, Shoichiro; Yamamoto, Masayuki; Sobue, Kenji; Shimizu, Atsushi

2016-01-01

Differences in DNA collection protocols may be a potential confounder in epigenome-wide association studies (EWAS) using a large number of blood specimens from multiple biobanks and/or cohorts. Here we show that pre-analytical procedures involved in DNA collection can induce systematic bias in the DNA methylation profiles of blood cells that can be adjusted by cell-type composition variables. In Experiment 1, whole blood from 16 volunteers was collected to examine the effect of a 24 h storage period at 4°C on DNA methylation profiles as measured using the Infinium HumanMethylation450 BeadChip array. Our statistical analysis showed that the P-value distribution of more than 450,000 CpG sites was similar to the theoretical distribution (in quantile-quantile plot, λ = 1.03) when comparing two control replicates, which was remarkably deviated from the theoretical distribution (λ = 1.50) when comparing control and storage conditions. We then considered cell-type composition as a possible cause of the observed bias in DNA methylation profiles and found that the bias associated with the cold storage condition was largely decreased (λ adjusted = 1.14) by taking into account a cell-type composition variable. As such, we compared four respective sample collection protocols used in large-scale Japanese biobanks or cohorts as well as two control replicates. Systematic biases in DNA methylation profiles were observed between control and three of four protocols without adjustment of cell-type composition (λ = 1.12-1.45) and no remarkable biases were seen after adjusting for cell-type composition in all four protocols (λ adjusted = 1.00-1.17). These results revealed important implications for comparing DNA methylation profiles between blood specimens from different sources and may lead to discovery of disease-associated DNA methylation markers and the development of DNA methylation profile-based predictive risk models.

DEMONSTRATION OF LOW COST, LOW BURDEN EXPOSURE MONITORING STRATEGIES FOR USE IN LONGITUDINAL COHORT STUDIES

EPA Science Inventory

A large longitudinal cohort study designed to evaluate the association between children's exposures to environmental agents and health outcomes presents many challenges for exposure monitoring. Exposure of the child must be measured for multiple chemicals through multiple path...

Effect of urate-lowering therapies on renal disease progression in patients with hyperuricemia.

PubMed

Levy, Gerald D; Rashid, Nazia; Niu, Fang; Cheetham, T Craig

2014-05-01

To evaluate the association between hyperuricemia and renal disease progression in a real-world, large observational database study. We conducted a population-based retrospective cohort study identifying 111,992 patients with hyperuricemia (> 7 mg/dl) from a large medical group. The final cohort were ≥ 18 years old, urate-lowering therapy (ULT)-naïve, and had the following laboratory results available: at least 1 glomerular filtration rate (GFR) level before the index date and at least 1 serum uric acid (sUA) level and GFR in the followup 36-month period. The cohort was categorized into 3 groups: never treated (NoTx), ULT time receiving therapy of < 80% (< 80%), and ULT time receiving therapy of ≥ 80% (≥ 80%). Outcomes were defined as a ≥ 30% reduction in GFR from baseline, dialysis, or GFR of ≤ 15 ml/min. A subanalysis of patients with sUA < 6 mg/dl at study conclusion was performed. Cox proportional hazards regression model determined factors associated with renal function decline. A total of 16,186 patients met inclusion criteria. There were 11,192 NoTx patients, 3902 with < 80% time receiving ULT, and 1092 with ≥ 80% time receiving ULT. Factors associated with renal disease progression were age, sex, hypertension, diabetes, congestive heart failure, hospitalizations, rheumatoid arthritis, and higher sUA at baseline. Time receiving therapy was not associated with renal outcomes. Patients who achieved sUA < 6 mg/dl had a 37% reduction in outcome events (p < 0.0001; HR 0.63, 95% CI: 0.5-0.78). Hyperuricemia is an independent risk factor for renal function decline. Patients treated with ULT who achieved sUA < 6 mg/dl on ULT showed a 37% reduction in outcome events.

Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessing SPP1 and LTBP4 variants.

PubMed

van den Bergen, Janneke C; Hiller, Monika; Böhringer, Stefan; Vijfhuizen, Linda; Ginjaar, Hendrika B; Chaouch, Amina; Bushby, Kate; Straub, Volker; Scoto, Mariacristina; Cirak, Sebahattin; Humbertclaude, Véronique; Claustres, Mireille; Scotton, Chiara; Passarelli, Chiara; Lochmüller, Hanns; Muntoni, Francesco; Tuffery-Giraud, Sylvie; Ferlini, Alessandra; Aartsma-Rus, Annemieke M; Verschuuren, Jan J G M; 't Hoen, Peter Ac; Spitali, Pietro

2015-10-01

Duchenne muscular dystrophy (DMD) is characterised by progressive muscle weakness. It has recently been reported that single nucleotide polymorphisms (SNPs) located in the SPP1 and LTBP4 loci can account for some of the inter-individual variability observed in the clinical disease course. The validation of genetic association in large independent cohorts is a key process for rare diseases in order to qualify prognostic biomarkers and stratify patients in clinical trials. Duchenne patients from five European neuromuscular centres were included. Information about age at wheelchair dependence and steroid use was gathered. Melting curve analysis of PCR fragments or Sanger sequencing were used to genotype SNP rs28357094 in the SPP1 gene in 336 patients. The genotype of SNPs rs2303729, rs1131620, rs1051303 and rs10880 in the LTBP4 locus was determined in 265 patients by mass spectrometry. For both loci, a multivariate analysis was performed, using genotype/haplotype, steroid use and cohort as covariates. We show that corticosteroid treatment and the IAAM haplotype of the LTBP4 gene are significantly associated with prolonged ambulation in patients with DMD. There was no significant association between the SNP rs28357094 in the SPP1 gene and the age of ambulation loss. This study underlines the importance of replicating genetic association studies for rare diseases in large independent cohorts to identify the most robust associations. We anticipate that genotyping of validated genetic associations will become important for the design and interpretation of clinical trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Non-HACEK gram-negative bacillus endocarditis.

PubMed

Morpeth, Susan; Murdoch, David; Cabell, Christopher H; Karchmer, Adolf W; Pappas, Paul; Levine, Donald; Nacinovich, Francisco; Tattevin, Pierre; Fernández-Hidalgo, Núria; Dickerman, Stuart; Bouza, Emilio; del Río, Ana; Lejko-Zupanc, Tatjana; de Oliveira Ramos, Auristela; Iarussi, Diana; Klein, John; Chirouze, Catherine; Bedimo, Roger; Corey, G Ralph; Fowler, Vance G

2007-12-18

Infective endocarditis caused by non-HACEK (species other than Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kingella species) gram-negative bacilli is rare, is poorly characterized, and is commonly considered to be primarily a disease of injection drug users. To describe the clinical characteristics and outcomes of patients with non-HACEK gram-negative bacillus endocarditis in a large, international, contemporary cohort of patients. Observations from the International Collaboration on Infective Endocarditis Prospective Cohort Study (ICE-PCS) database. 61 hospitals in 28 countries. Hospitalized patients with definite endocarditis. Characteristics of non-HACEK gram-negative bacillus endocarditis cases were described and compared with those due to other pathogens. Among the 2761 case-patients with definite endocarditis enrolled in ICE-PCS, 49 (1.8%) had endocarditis (20 native valve, 29 prosthetic valve or device) due to non-HACEK, gram-negative bacilli. Escherichia coli (14 patients [29%]) and Pseudomonas aeruginosa (11 patients [22%]) were the most common pathogens. Most patients (57%) with non-HACEK gram-negative bacillus endocarditis had health care-associated infection, whereas injection drug use was rare (4%). Implanted endovascular devices were frequently associated with non-HACEK gram-negative bacillus endocarditis compared with other causes of endocarditis (29% vs. 11%; P < 0.001). The in-hospital mortality rate of patients with endocarditis due to non-HACEK gram-negative bacilli was high (24%) despite high rates of cardiac surgery (51%). Because of the small number of patients with non-HACEK gram-negative bacillus endocarditis in each treatment group and the lack of long-term follow-up, strong treatment recommendations are difficult to make. In this large, prospective, multinational cohort, more than one half of all cases of non-HACEK gram-negative bacillus endocarditis were associated with health care contact. Non-HACEK gram-negative bacillus endocarditis is not primarily a disease of injection drug users.

Interest of a simple on-line screening registry for measuring ICU burden related to an influenza pandemic.

PubMed

Richard, Jean-Christophe Marie; Pham, Tài; Brun-Buisson, Christian; Reignier, Jean; Mercat, Alain; Beduneau, Gaëtan; Régnier, Bernard; Mourvillier, Bruno; Guitton, Christophe; Castanier, Matthias; Combes, Alain; Le Tulzo, Yves; Brochard, Laurent

2012-07-09

The specific burden imposed on Intensive Care Units (ICUs) during the A/H1N1 influenza 2009 pandemic has been poorly explored. An on-line screening registry allowed a daily report of ICU beds occupancy rate by flu infected patients (Flu-OR) admitted in French ICUs. We conducted a prospective inception cohort study with results of an on-line screening registry designed for daily assessment of ICU burden. Among the 108 centers participating to the French H1N1 research network on mechanical ventilation (REVA) - French Society of Intensive Care (SRLF) registry, 69 ICUs belonging to seven large geographical areas voluntarily participated in a website screening-registry. The aim was to daily assess the ICU beds occupancy rate by influenza-infected and non-infected patients for at least three weeks. Three hundred ninety-one critically ill infected patients were enrolled in the cohort, representing a subset of 35% of the whole French 2009 pandemic cohort; 73% were mechanically ventilated, 13% required extra corporal membrane oxygenation (ECMO) and 22% died. The global Flu-OR in these ICUs was only 7.6%, but it exceeded a predefined 15% critical threshold in 32 ICUs for a total of 103 weeks. Flu-ORs were significantly higher in University than in non-University hospitals. The peak ICU burden was poorly predicted by observations obtained at the level of large geographical areas. The peak Flu-OR during the pandemic significantly exceeded a 15% critical threshold in almost half of the ICUs, with an uneven distribution with time, geographical areas and between University and non-University hospitals. An on-line assessment of Flu-OR via a simple dedicated registry may contribute to better match resources and needs.

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

Individual signatures and environmental factors shape skin microbiota in healthy dogs.

PubMed

Cuscó, Anna; Belanger, Janelle M; Gershony, Liza; Islas-Trejo, Alma; Levy, Kerinne; Medrano, Juan F; Sánchez, Armand; Oberbauer, Anita M; Francino, Olga

2017-10-13

The individual, together with its environment, has been reported as the main force driving composition and structure of skin microbiota in healthy dogs. Therefore, one of the major concerns when analyzing canine skin microbiota is the likely influence of the environment. Despite the dense fur covering, certain skin diseases exhibit differential prevalence among skin sites, dog breeds, and individuals. We have characterized the normal variability of dog skin microbiota in a well-controlled cohort of a large number of Golden-Labrador Retriever crossed dogs (N = 35) with similar ages, related genetic background, and a shared environment. We found that the individual drives the skin microbiota composition and structure followed by the skin site. The main bacterial classes inhabiting dog skin in this cohort are Gammaproteobacteria and Bacilli. We also detected bacteria associated to the environment on different dog skin sites that could be reflecting the different degrees of exposure of each skin site and each dog. Network analyses elucidated bacterial interactions within and between skin sites, especially in the chin, abdomen, axilla, and perianal region, with the highly shared interactions probably representing an anatomical, behavioral, or environmental component. When analyzing each skin site independently to assess host-specific factors, we found that temporality (season of birth and time spent in the kennel) affected all the skin sites and specially the inner pinna. The most abundant taxon driving this difference was Sphingomonas. We also found taxonomic differences among male and female dogs on the abdomen, axilla, and back. We observed a large inter-individual variability and differences among skin sites. Host-specific variables, such as temporality or sex, were also shaping skin microbiota of healthy dogs, even in an environmental homogenous cohort.

Evaluation of Buccal Cell Samples for Studies of Oral Microbiota.

PubMed

Yu, Guoqin; Phillips, Steve; Gail, Mitchell H; Goedert, James J; Humphrys, Michael; Ravel, Jacques; Ren, Yanfang; Caporaso, Neil E

2017-02-01

The human microbiota is postulated to affect cancer risk, but collecting microbiota specimens with prospective follow-up for diseases will take time. Buccal cell samples have been obtained from mouthwash for the study of human genomic DNA in many cohort studies. Here, we evaluate the feasibility of using buccal cell samples to examine associations of human microbiota and disease risk. We obtained buccal cells from mouthwash in 41 healthy participants using a protocol that is widely employed to obtain buccal cells for the study of human DNA. We compared oral microbiota from buccal cells with that from eight other oral sample types collected by following the protocols of the Human Microbiome Project. Microbiota profiles were determined by sequencing 16S rRNA gene V3-V4 region. Compared with each of the eight other oral samples, the buccal cell samples had significantly more observed species (P < 0.002) and higher alpha diversity (Shannon index, P < 0.02). The microbial communities were more similar (smaller beta diversity) among buccal cells samples than in the other samples (P < 0.001 for 12 of 16 weighted and unweighted UniFrac distance comparisons). Buccal cell microbial profiles closely resembled saliva but were distinct from dental plaque and tongue dorsum. Stored buccal cell samples in prospective cohort studies are a promising resource to study associations of oral microbiota with disease. The feasibility of using existing buccal cell collections in large prospective cohorts allows investigations of the role of oral microbiota in chronic disease etiology in large population studies possible today. Cancer Epidemiol Biomarkers Prev; 26(2); 249-53. ©2016 AACR. ©2016 American Association for Cancer Research.

Sickness absence due to otoaudiological diagnoses and risk of disability pension: a nationwide Swedish prospective cohort study.

PubMed

Friberg, Emilie; Jansson, Catarina; Mittendorfer-Rutz, Ellenor; Rosenhall, Ulf; Alexanderson, Kristina

2012-01-01

Hearing difficulties are a large public health problem. Knowledge is scarce regarding risk of disability pension among people who have been sickness absent due to these difficulties. A cohort including all 4,687,756 individuals living in Sweden in 2005, aged 20-64, and not on disability or old-age pension, was followed through 2009. Incidence rate ratios (RR) of disability pension with 95% confidence intervals (CI) were estimated using Cox proportional hazard models. In multivariable models, individuals who had a sick-leave spell due to otoaudiological diagnoses in 2005 had a 1.52-fold (95% CI: 1.43-1.62) increased risk of being granted a disability pension compared to individuals on sick leave due to other diagnoses. Hearing and tinnitus sick-leave diagnoses were associated with risk of disability pension: RR 3.38, 95% CI: 3.04-3.75, and 3.30, 95% CI: 2.95-3.68, respectively. No association was observed between sick leave due to vertigo diagnoses and disability pension whereas otological diagnoses and no sick leave were inversely associated with risk of disability pension compared to non-otoaudiological sick-leave diagnoses. Sick leave due to otoaudiological diagnoses was positively associated with risk of disability pension due to otoaudiological diagnoses and sick leave due to a tinnitus diagnosis was also associated with risk of disability pension due to mental diagnoses. The risk of disability pension among individuals with hearing or tinnitus sick-leave diagnoses was highest in the age group 35-44. Moreover, men had a slightly higher risk. This large cohort study suggests an increased risk of disability pension among those with sickness absence due to otoaudiological diagnoses, particularly hearing and tinnitus diagnoses, compared to those with sickness absence due to non-otoaudiological diagnoses.

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

Wang, Xusheng; Pandey, Ashutosh K.; Mulligan, Megan K.

Phenome-wide association is a novel reverse genetic strategy to analyze genome-to-phenome relations in human clinical cohorts. Here we test this approach using a large murine population segregating for ~5 million sequence variants, and we compare our results to those extracted from a matched analysis of gene variants in a large human cohort. For the mouse cohort, we amassed a deep and broad open-access phenome consisting of ~4,500 metabolic, physiological, pharmacological and behavioural traits, and more than 90 independent expression quantitative trait locus (QTL), transcriptome, proteome, metagenome and metabolome data sets-by far the largest coherent phenome for any experimental cohort (www.genenetwork.org).more » Here, we tested downstream effects of subsets of variants and discovered several novel associations, including a missense mutation in fumarate hydratase that controls variation in the mitochondrial unfolded protein response in both mouse and Caenorhabditis elegans, and missense mutations in Col6a5 that underlies variation in bone mineral density in both mouse and human.« less

Reference-based phasing using the Haplotype Reference Consortium panel.

PubMed

Loh, Po-Ru; Danecek, Petr; Palamara, Pier Francesco; Fuchsberger, Christian; A Reshef, Yakir; K Finucane, Hilary; Schoenherr, Sebastian; Forer, Lukas; McCarthy, Shane; Abecasis, Goncalo R; Durbin, Richard; L Price, Alkes

2016-11-01

Haplotype phasing is a fundamental problem in medical and population genetics. Phasing is generally performed via statistical phasing in a genotyped cohort, an approach that can yield high accuracy in very large cohorts but attains lower accuracy in smaller cohorts. Here we instead explore the paradigm of reference-based phasing. We introduce a new phasing algorithm, Eagle2, that attains high accuracy across a broad range of cohort sizes by efficiently leveraging information from large external reference panels (such as the Haplotype Reference Consortium; HRC) using a new data structure based on the positional Burrows-Wheeler transform. We demonstrate that Eagle2 attains a ∼20× speedup and ∼10% increase in accuracy compared to reference-based phasing using SHAPEIT2. On European-ancestry samples, Eagle2 with the HRC panel achieves >2× the accuracy of 1000 Genomes-based phasing. Eagle2 is open source and freely available for HRC-based phasing via the Sanger Imputation Service and the Michigan Imputation Server.

Joint mouse–human phenome-wide association to test gene function and disease risk

DOE PAGES

Wang, Xusheng; Pandey, Ashutosh K.; Mulligan, Megan K.; ...

2016-02-02

Phenome-wide association is a novel reverse genetic strategy to analyze genome-to-phenome relations in human clinical cohorts. Here we test this approach using a large murine population segregating for ~5 million sequence variants, and we compare our results to those extracted from a matched analysis of gene variants in a large human cohort. For the mouse cohort, we amassed a deep and broad open-access phenome consisting of ~4,500 metabolic, physiological, pharmacological and behavioural traits, and more than 90 independent expression quantitative trait locus (QTL), transcriptome, proteome, metagenome and metabolome data sets-by far the largest coherent phenome for any experimental cohort (www.genenetwork.org).more » Here, we tested downstream effects of subsets of variants and discovered several novel associations, including a missense mutation in fumarate hydratase that controls variation in the mitochondrial unfolded protein response in both mouse and Caenorhabditis elegans, and missense mutations in Col6a5 that underlies variation in bone mineral density in both mouse and human.« less

Historical clinical and economic consequences of anemia management in patients with end-stage renal disease on dialysis using erythropoietin stimulating agents versus routine blood transfusions: a retrospective cost-effectiveness analysis.

PubMed

Naci, Huseyin; de Lissovoy, Gregory; Hollenbeak, Christopher; Custer, Brian; Hofmann, Axel; McClellan, William; Gitlin, Matthew

2012-01-01

To determine whether Medicare's decision to cover routine administration of erythropoietin stimulating agents (ESAs) to treat anemia of end-stage renal disease (ESRD) has been a cost-effective policy relative to standard of care at the time. The authors used summary statistics from the actual cohort of ESRD patients receiving ESAs between 1995 and 2004 to create a simulated patient cohort, which was compared with a comparable simulated cohort assumed to rely solely on blood transfusions. Outcomes modeled from the Medicare perspective included estimated treatment costs, life-years gained, and quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratio (ICER) was calculated relative to the hypothetical reference case of no ESA use in the transfusion cohort. Sensitivity of the results to model assumptions was tested using one-way and probabilistic sensitivity analyses. Estimated total costs incurred by the ESRD population were $155.47B for the cohort receiving ESAs and $155.22B for the cohort receiving routine blood transfusions. Estimated QALYs were 2.56M and 2.29M, respectively, for the two groups. The ICER of ESAs compared to routine blood transfusions was estimated as $873 per QALY gained. The model was sensitive to a number of parameters according to one-way and probabilistic sensitivity analyses. This model was counter-factual as the actual comparison group, whose anemia was managed via transfusion and iron supplements, rapidly disappeared following introduction of ESAs. In addition, a large number of model parameters were obtained from observational studies due to the lack of randomized trial evidence in the literature. This study indicates that Medicare's coverage of ESAs appears to have been cost effective based on commonly accepted levels of willingness-to-pay. The ESRD population achieved substantial clinical benefit at a reasonable cost to society.

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.

HIV incidence and risk factors in Chinese young men who have sex with men--a prospective cohort study.

PubMed

Dong, Zhenxin; Xu, Jie; Zhang, Hongbo; Dou, Zhi; Mi, Guodong; Ruan, Yuhua; Shen, Limei; Min, Xiangdong; Lan, Guanghua; Li, Fan; Li, Tian; Ning, Zhen; Wu, Guohui; She, Min; Wu, Zunyou

2014-01-01

To assess HIV incidence and its associated risk factors among young men who have sex with men (YMSM) in urban areas, China. The study used a prospective cohort study design and standard diagnostic tests. A twelve-month prospective cohort study was conducted among YMSM (18-25 years old) in 8 large cities in China. The participants were recruited via snowball sampling. A total of 1102 HIV-negative YMSM completed baseline assessment, 878 YMSM participants completed 6-month follow-up, and 902 completed 12-month follow-up. HIV was screened by an enzyme-linked immunosorbent assay and confirmed with Western Blot. Syphilis was screened via rapid plasma reagent and confirmed by treponema pallidum particle agglutination assay. 78 HIV seroconversions were identified within 1168.4 person-year observations yielding an incidence rate of 6.7 per 100 person-years. HIV seroconversion was associated with non-student status (RR = 2.61, 90% CI = 1.3-5.26), low HIV transmission knowledge (RR = 8.87, 90% CI = 2.16-36.43), and syphilis infection (RR = 5.04, 90% CI = 2.57-9.90). Incidence of HIV among YMSM is high in urban areas of China. Interventions measures are required to contain the HIV epidemic within this population.

Plasma carotenoids, retinol, and tocopherols and postmenopausal breast cancer risk in the Multiethnic Cohort Study: a nested case-control study

PubMed Central

Epplein, Meira; Shvetsov, Yurii B; Wilkens, Lynne R; Franke, Adrian A; Cooney, Robert V; Le Marchand, Loïc; Henderson, Brian E; Kolonel, Laurence N; Goodman, Marc T

2009-01-01

Introduction Assessments by the handful of prospective studies of the association of serum antioxidants and breast cancer risk have yielded inconsistent results. This multiethnic nested case-control study sought to examine the association of plasma carotenoids, retinol, and tocopherols with postmenopausal breast cancer risk. Methods From the biospecimen subcohort of the Multiethnic Cohort Study, 286 incident postmenopausal breast cancer cases were matched to 535 controls on age, sex, ethnicity, study location (Hawaii or California), smoking status, date/time of collection and hours of fasting. We measured prediagnostic circulating levels of individual carotenoids, retinol, and tocopherols. Conditional logistic regression was used to compute odds ratios and 95% confidence intervals. Results Women with breast cancer tended to have lower levels of plasma carotenoids and tocopherols than matched controls, but the differences were not large or statistically significant and the trends were not monotonic. No association was seen with retinol. A sensitivity analysis excluding cases diagnosed within 1 year after blood draw did not alter the findings. Conclusions The lack of significant associations in this multiethnic population is consistent with previously observed results from less racially-diverse cohorts and serves as further evidence against a causal link between plasma micronutrient concentrations and postmenopausal breast cancer risk. PMID:19619335

Following the footprints of polymorphic inversions on SNP data: from detection to association tests

PubMed Central

Cáceres, Alejandro; González, Juan R.

2015-01-01

Inversion polymorphisms have important phenotypic and evolutionary consequences in humans. Two different methodologies have been used to infer inversions from SNP dense data, enabling the use of large cohorts for their study. One approach relies on the differences in linkage disequilibrium across breakpoints; the other one captures the internal haplotype groups that tag the inversion status of chromosomes. In this article, we assessed the convergence of the two methods in the detection of 20 human inversions that have been reported in the literature. The methods converged in four inversions including inv-8p23, for which we studied its association with low-BMI in American children. Using a novel haplotype tagging method with control on inversion ancestry, we computed the frequency of inv-8p23 in two American cohorts and observed inversion haplotype admixture. Accounting for haplotype ancestry, we found that the European inverted allele in children carries a recessive risk of underweight, validated in an independent Spanish cohort (combined: OR= 2.00, P = 0.001). While the footprints of inversions on SNP data are complex, we show that systematic analyses, such as convergence of different methods and controlling for ancestry, can reveal the contribution of inversions to the ancestral composition of populations and to the heritability of human disease. PMID:25672393

Implementation of a Longitudinal Introduction to Radiology Course During Internship Year Improves Diagnostic Radiology Residents' Academic and Clinical Skills: A Canadian Experience.

PubMed

Darras, Kathryn E; Worthington, Anne; Russell, David; Hou, Daniel J; Forster, Bruce B; Hague, Cameron J; Mar, Colin; Chang, Silvia D

2016-07-01

In order to ease the transition from internship to diagnostic radiology residency, a year-long didactic introduction to radiology course was offered to post-graduate year one (PGY-1) diagnostic radiology residents during their internship, which consisted of 27 hours of lecture over 9 months. The purpose of this study was to determine the quantitative and qualitative educational value of this course and its effect with respect to on-call preparedness. Two consecutive cohorts of Diagnostic Radiology residents were included: the first cohort (PGY-1s in 2011-2012) did not participate in the new course (Old Curriculum Residents) and the second cohort (PGY-1s in 2012-2013) completed the new course (New Curriculum Residents). These two cohorts were compared both qualitatively and quantitatively. Scores were compared from the standardized Canadian National Pre-Call Observed Standardized Clinical Examination and American College of Radiology Diagnostic Radiology In-Training examination, which are taken in the PGY-2 year, at months 5 and 7, respectively. In addition, staff observation of on-call resident performance and resident self-reported preparedness were considered. Cohorts were compared using Mann-Whitney U test with significance defined as P value <0.05. P values from 0.05 to 0.10 were noted as possibly significant and further analyzed using a Cohen d test where the difference was determined to be small (0.2), medium (0.5), or large (0.8). New Curriculum Residents reported that the content of the PGY1 curriculum was more appropriate than the old curriculum to prepare them for call in PGY2 (P = 0.013). New Curriculum Residents scored better than the Old Curriculum Residents on the Diagnostic Radiology In-Training examination (P = 0.039) and on the emergency cases of the Canadian National Pre-Call Observed Standardized Clinical Examination (P = 0.035). Staff radiologists, who were not blinded, reported that the New Curriculum Residents were better prepared for daytime (P = 0.006) and overnight (P = 0.008) independent call were better prepared to perform common ultrasound examinations alone (P = 0.049), and required less guidance while on call for nine competency areas. There was, however, no statistical difference between the residents' self-reported preparedness for independent call. Participation in a lecture-based introductory radiology curriculum during the PGY-1 internship year improved both radiology residents' preparedness for call and their performance in PGY-2. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Sedentary behavior and physical activity in youth with recent onset of type 2 diabetes.

PubMed

Kriska, Andrea; Delahanty, Linda; Edelstein, Sharon; Amodei, Nancy; Chadwick, Jennifer; Copeland, Kenneth; Galvin, Bryan; El ghormli, Laure; Haymond, Morey; Kelsey, Megan; Lassiter, Chad; Mayer-Davis, Elizabeth; Milaszewski, Kerry; Syme, Amy

2013-03-01

With the rise of type 2 diabetes in youth, it is critical to investigate factors such as physical activity (PA) and time spent sedentary that may be contributing to this public health problem. This article describes PA and sedentary time in a large cohort of youth with type 2 diabetes and compares these levels with other large-scale investigations. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial is a study in 699 youth, recruited from 15 US clinical centers, aged 10 to 17 years with <2 years of type 2 diabetes and a BMI ≥85th percentile. In comparison with the subset of the NHANES cohort who were obese (BMI ≥95th percentile), TODAY youth spent significantly more time being sedentary (difference averaging 56 minutes per day; P < .001) as assessed by accelerometry. Although moderate to vigorous activity levels in both obese cohorts for all age groups were exceptionally low, younger TODAY boys were still significantly less active than similarly aged NHANES youth. Comparisons between the TODAY girls and other investigations suggest that the TODAY girls also had relatively lower PA and fitness levels. Adolescents with type 2 diabetes from the large TODAY cohort appear to be less physically active and tend to spend more time being sedentary than similarly aged youth without diabetes identified from other large national investigations. Treatment efforts in adolescents with type 2 diabetes should include decreasing sitting along with efforts to increase PA levels.

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.

Cohort profile: the Geoscience and Health Cohort Consortium (GECCO) in the Netherlands.

PubMed

Timmermans, Erik J; Lakerveld, Jeroen; Beulens, Joline W J; Boomsma, Dorret I; Kramer, Sophia E; Oosterman, Mirjam; Willemsen, Gonneke; Stam, Mariska; Nijpels, Giel; Schuengel, Carlo; Smit, Jan H; Brunekreef, Bert; Dekkers, Jasper E C; Deeg, Dorly J H; Penninx, Brenda W J H; Huisman, Martijn

2018-06-09

In the Netherlands, a great variety of objectively measured geo-data is available, but these data are scattered and measured at varying spatial and temporal scales. The centralisation of these geo-data and the linkage of these data to individual-level data from longitudinal cohort studies enable large-scale epidemiological research on the impact of the environment on public health in the Netherlands. In the Geoscience and Health Cohort Consortium (GECCO), six large-scale and ongoing cohort studies have been enriched with a variety of existing geo-data. Here, we introduce GECCO by describing: (1) the phenotypes of the involved cohort studies, (2) the collected geo-data and their sources, (3) the methodology that was used to link the collected geo-data to individual cohort studies, (4) the similarity of commonly used geo-data between our consortium and the nationwide situation in the Netherlands and (5) the distribution of geo-data within our consortium. GECCO includes participants from six prospective cohort studies (eg, 44 657 respondents (18-100 years) in 2006) and it covers all municipalities in the Netherlands. Using postal code information of the participants, geo-data on the address-level, postal code-level as well as neighbourhood-level could be linked to individual-level cohort data. The geo-data could be successfully linked to almost all respondents of all cohort studies, with successful data-linkage rates ranging from 97.1% to 100.0% between cohort studies. The results show variability in geo-data within and across cohorts. GECCO increases power of analyses, provides opportunities for cross-checking and replication, ensures sufficient geographical variation in environmental determinants and allows for nuanced analyses on specific subgroups. GECCO offers unique opportunities for (longitudinal) studies on the complex relationships between the environment and health outcomes. For example, GECCO will be used for further research on environmental determinants of physical/psychosocial functioning and lifestyle behaviours. © 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.

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.

Large-scale serum protein biomarker discovery in Duchenne muscular dystrophy.

PubMed

Hathout, Yetrib; Brody, Edward; Clemens, Paula R; Cripe, Linda; DeLisle, Robert Kirk; Furlong, Pat; Gordish-Dressman, Heather; Hache, Lauren; Henricson, Erik; Hoffman, Eric P; Kobayashi, Yvonne Monique; Lorts, Angela; Mah, Jean K; McDonald, Craig; Mehler, Bob; Nelson, Sally; Nikrad, Malti; Singer, Britta; Steele, Fintan; Sterling, David; Sweeney, H Lee; Williams, Steve; Gold, Larry

2015-06-09

Serum biomarkers in Duchenne muscular dystrophy (DMD) may provide deeper insights into disease pathogenesis, suggest new therapeutic approaches, serve as acute read-outs of drug effects, and be useful as surrogate outcome measures to predict later clinical benefit. In this study a large-scale biomarker discovery was performed on serum samples from patients with DMD and age-matched healthy volunteers using a modified aptamer-based proteomics technology. Levels of 1,125 proteins were quantified in serum samples from two independent DMD cohorts: cohort 1 (The Parent Project Muscular Dystrophy-Cincinnati Children's Hospital Medical Center), 42 patients with DMD and 28 age-matched normal volunteers; and cohort 2 (The Cooperative International Neuromuscular Research Group, Duchenne Natural History Study), 51 patients with DMD and 17 age-matched normal volunteers. Forty-four proteins showed significant differences that were consistent in both cohorts when comparing DMD patients and healthy volunteers at a 1% false-discovery rate, a large number of significant protein changes for such a small study. These biomarkers can be classified by known cellular processes and by age-dependent changes in protein concentration. Our findings demonstrate both the utility of this unbiased biomarker discovery approach and suggest potential new diagnostic and therapeutic avenues for ameliorating the burden of DMD and, we hope, other rare and devastating diseases.

Mobile spine chordoma: results of 166 patients from the AOSpine Knowledge Forum Tumor database.

PubMed

Gokaslan, Ziya L; Zadnik, Patricia L; Sciubba, Daniel M; Germscheid, Niccole; Goodwin, C Rory; Wolinsky, Jean-Paul; Bettegowda, Chetan; Groves, Mari L; Luzzati, Alessandro; Rhines, Laurence D; Fisher, Charles G; Varga, Peter Pal; Dekutoski, Mark B; Clarke, Michelle J; Fehlings, Michael G; Quraishi, Nasir A; Chou, Dean; Reynolds, Jeremy J; Williams, Richard P; Kawahara, Norio; Boriani, Stefano

2016-04-01

A chordoma is an indolent primary spinal tumor that has devastating effects on the patient's life. These lesions are chemoresistant, resistant to conventional radiotherapy, and moderately sensitive to proton therapy; however, en bloc resection remains the preferred treatment for optimizing patient outcomes. While multiple small and largely retrospective studies have investigated the outcomes following en bloc resection of chordomas in the sacrum, there have been few large-scale studies on patients with chordomas of the mobile spine. The goal of this study was to review the outcomes of surgically treated patients with mobile spine chordomas at multiple international centers with respect to local recurrence and survival. This multiinstitutional retrospective study collected data between 1988 and 2012 about prognosis-predicting factors, including various clinical characteristics and surgical techniques for mobile spine chordoma. Tumors were classified according to the Enneking principles and analyzed in 2 treatment cohorts: Enneking-appropriate (EA) and Enneking-inappropriate (EI) cohorts. Patients were categorized as EA when the final pathological assessment of the margin matched the Enneking recommendation; otherwise, they were categorized as EI. Descriptive statistics were used to summarize the data (Student t-test, chi-square, and Fisher exact tests). Recurrence and survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and multivariate Cox proportional hazard modeling. A total of 166 patients (55 female and 111 male patients) with mobile spine chordoma were included. The median patient follow-up was 2.6 years (range 1 day to 22.5 years). Fifty-eight (41%) patients were EA and 84 (59%) patients were EI. The type of biopsy (p < 0.001), spinal location (p = 0.018), and if the patient received adjuvant therapy (p < 0.001) were significantly different between the 2 cohorts. Overall, 58 (35%) patients developed local recurrence and 57 (34%) patients died. Median survival was 7.0 years postoperative: 8.4 years postoperative for EA patients and 6.4 years postoperative for EI patients (p = 0.023). The multivariate analysis showed that the EI cohort was significantly associated with an increased risk of local recurrence in comparison with the EA cohort (HR 7.02; 95% CI 2.96-16.6; p < 0.001), although no significant difference in survival was observed. EA resection plays a major role in decreasing the risk for local recurrence in patients with chordoma of the mobile spine.

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.

Genome-Wide Gene Expression in relation to Age in Large Laboratory Cohorts of Drosophila melanogaster

PubMed Central

Carlson, Kimberly A.; Gardner, Kylee; Pashaj, Anjeza; Carlson, Darby J.; Yu, Fang; Eudy, James D.; Zhang, Chi; Harshman, Lawrence G.

2015-01-01

Aging is a complex process characterized by a steady decline in an organism's ability to perform life-sustaining tasks. In the present study, two cages of approximately 12,000 mated Drosophila melanogaster females were used as a source of RNA from individuals sampled frequently as a function of age. A linear model for microarray data method was used for the microarray analysis to adjust for the box effect; it identified 1,581 candidate aging genes. Cluster analyses using a self-organizing map algorithm on the 1,581 significant genes identified gene expression patterns across different ages. Genes involved in immune system function and regulation, chorion assembly and function, and metabolism were all significantly differentially expressed as a function of age. The temporal pattern of data indicated that gene expression related to aging is affected relatively early in life span. In addition, the temporal variance in gene expression in immune function genes was compared to a random set of genes. There was an increase in the variance of gene expression within each cohort, which was not observed in the set of random genes. This observation is compatible with the hypothesis that D. melanogaster immune function genes lose control of gene expression as flies age. PMID:26090231

Are the studies on cancer risk from CT scans biased by indication? Elements of answer from a large-scale cohort study in France.

PubMed

Journy, N; Rehel, J-L; Ducou Le Pointe, H; Lee, C; Brisse, H; Chateil, J-F; Caer-Lorho, S; Laurier, D; Bernier, M-O

2015-01-06

Recent epidemiological results suggested an increase of cancer risk after receiving computed tomography (CT) scans in childhood or adolescence. Their interpretation is questioned due to the lack of information about the reasons for examination. Our objective was to estimate the cancer risk related to childhood CT scans, and examine how cancer-predisposing factors (PFs) affect assessment of the radiation-related risk. The cohort included 67,274 children who had a first scan before the age of 10 years from 2000 to 2010 in 23 French departments. Cumulative X-rays doses were estimated from radiology protocols. Cancer incidence was retrieved through the national registry of childhood cancers; PF from discharge diagnoses. During a mean follow-up of 4 years, 27 cases of tumours of the central nervous system, 25 of leukaemia and 21 of lymphoma were diagnosed; 32% of them among children with PF. Specific patterns of CT exposures were observed according to PFs. Adjustment for PF reduced the excess risk estimates related to cumulative doses from CT scans. No significant excess risk was observed in relation to CT exposures. This study suggests that the indication for examinations, whether suspected cancer or PF management, should be considered to avoid overestimation of the cancer risks associated with CT scans.

Impact of genetic variants on haematopoiesis in patients with thrombocytopenia absent radii (TAR) syndrome.

PubMed

Manukjan, Georgi; Bösing, Hendrik; Schmugge, Markus; Strauß, Gabriele; Schulze, Harald

2017-11-01

Thrombocytopenia absent radii (TAR) syndrome is clearly defined by the combination of radial aplasia and reduced platelet counts. The genetics of TAR syndrome has recently been resolved and comprises a microdeletion on Chromosome 1 including the RBM8A gene and a single nucleotide polymorphism (SNP) either at the 5' untranslated region (5'UTR) or within the first intron of RBM8A. Although phenotypically readily diagnosed after birth, the genetic determination of particular SNPs in TAR syndrome harbours valuable information to evaluate disease severity and treatment decisions. Here, we present clinical data in a cohort of 38 patients and observed that platelet counts in individuals with 5'UTR SNP are significantly lower compared to patients bearing the SNP in intron 1. Moreover, elevated haemoglobin values could only be assessed in patients with 5'UTR SNP whereas white blood cell count is unaffected, indicating that frequently observed anaemia in TAR patients could also be SNP-dependent whereas leucocytosis does not correlate with genetic background. However, this report on a large cohort provides an overview of important haematological characteristics in TAR patients, facilitating evaluation of the various traits in this disease and indicating the importance of genetic validation for TAR syndrome. © 2017 John Wiley & Sons Ltd.

Marginal Structural Cox Models for Estimating the Association Between β-Interferon Exposure and Disease Progression in a Multiple Sclerosis Cohort

PubMed Central

Karim, Mohammad Ehsanul; Gustafson, Paul; Petkau, John; Zhao, Yinshan; Shirani, Afsaneh; Kingwell, Elaine; Evans, Charity; van der Kop, Mia; Oger, Joel; Tremlett, Helen

2014-01-01

Longitudinal observational data are required to assess the association between exposure to β-interferon medications and disease progression among relapsing-remitting multiple sclerosis (MS) patients in the “real-world” clinical practice setting. Marginal structural Cox models (MSCMs) can provide distinct advantages over traditional approaches by allowing adjustment for time-varying confounders such as MS relapses, as well as baseline characteristics, through the use of inverse probability weighting. We assessed the suitability of MSCMs to analyze data from a large cohort of 1,697 relapsing-remitting MS patients in British Columbia, Canada (1995–2008). In the context of this observational study, which spanned more than a decade and involved patients with a chronic yet fluctuating disease, the recently proposed “normalized stabilized” weights were found to be the most appropriate choice of weights. Using this model, no association between β-interferon exposure and the hazard of disability progression was found (hazard ratio = 1.36, 95% confidence interval: 0.95, 1.94). For sensitivity analyses, truncated normalized unstabilized weights were used in additional MSCMs and to construct inverse probability weight-adjusted survival curves; the findings did not change. Additionally, qualitatively similar conclusions from approximation approaches to the weighted Cox model (i.e., MSCM) extend confidence in the findings. PMID:24939980

Benign Breast Disease: Toward Molecular Prediction of Breast Cancer Risk

DTIC Science & Technology

2007-06-01

progress on these aims. Our current cohort comprises 9,376 women , 758 (8%) of whom have been diagnosed with breast cancer since the time of their benign... women . Our focus in 2007-2008 will be on the Wayne State cohort and exploring additional molecular markers. 15. SUBJECT TERMS benign breast disease...Excellence: 1) the establishment of a large tissue repository from a retrospective cohort of women with benign breast disease (BBD) (1967-1991); 2

Comparison of fasting and non-fasting lipid profiles in a large cohort of patients presenting at a community hospital.

PubMed

Cartier, Louis-Jacques; Collins, Charlene; Lagacé, Mathieu; Douville, Pierre

2018-02-01

To compare the fasting and non-fasting lipid profile including ApoB in a cohort of patients from a community setting. Our purpose was to determine the proportion of results that could be explained by the known biological variation in the fasting state and to examine the additional impact of non-fasting on these same lipid parameters. 1093 adult outpatients with fasting lipid requests were recruited from February to September 2016 at the blood collection sites of the Moncton Hospital. Participants were asked to come back in the next 3-4days after having eaten a regular breakfast to have their blood drawn for a non-fasting lipid profile. 91.6% of patients in this study had a change in total cholesterol that fell within the biological variation expected for this parameter. Similar results were seen for HDL-C (94.3%) non-HDL-C (88.8%) and ApoB (93.0%). A smaller number of patients fell within the biological variation expected for TG (78.8%) and LDL-C (74.6%). An average TG increase of 0.3mmol/L was observed in fed patients no matter the level of fasting TG. A gradual widening in the range of change in TG concentration was observed as fasting TG increased. Similar results were seen in diabetic patients. Outside of LDL-C and TG, little changes were seen in lipid parameters in the postprandial state. A large part of these changes could be explained by the biological variation. We observed a gradual widening in the range of increase in TG for patients with higher fasting TG. Non-HDL-C and ApoB should be the treatment target of choice for patients in the non-fasting state. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Cerebral palsy in Victoria: motor types, topography and gross motor function.

PubMed

Howard, Jason; Soo, Brendan; Graham, H Kerr; Boyd, Roslyn N; Reid, Sue; Lanigan, Anna; Wolfe, Rory; Reddihough, Dinah S

2005-01-01

To study the relationships between motor type, topographical distribution and gross motor function in a large, population-based cohort of children with cerebral palsy (CP), from the State of Victoria, and compare this cohort to similar cohorts from other countries. An inception cohort was generated from the Victorian Cerebral Palsy Register (VCPR) for the birth years 1990-1992. Demographic information, motor types and topographical distribution were obtained from the register and supplemented by grading gross motor function according to the Gross Motor Function Classification System (GMFCS). Complete data were obtained on 323 (86%) of 374 children in the cohort. Gross motor function varied from GMFCS level I (35%) to GMFCS level V (18%) and was similar in distribution to a contemporaneous Swedish cohort. There was a fairly even distribution across the topographical distributions of hemiplegia (35%), diplegia (28%) and quadriplegia (37%) with a large majority of young people having the spastic motor type (86%). The VCPR is ideal for population-based studies of gross motor function in children with CP. Gross motor function is similar in populations of children with CP in developed countries but the comparison of motor types and topographical distribution is difficult because of lack of consensus with classification systems. Use of the GMFCS provides a valid and reproducible method for clinicians to describe gross motor function in children with CP using a universal language.

Nordic registry-based cohort studies: Possibilities and pitfalls when combining Nordic registry data.

PubMed

Maret-Ouda, John; Tao, Wenjing; Wahlin, Karl; Lagergren, Jesper

2017-07-01

All five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) have nationwide registries with similar data structure and validity, as well as personal identity numbers enabling linkage between registries. These resources provide opportunities for medical research that is based on large registry-based cohort studies with long and complete follow-up. This review describes practical aspects, opportunities and challenges encountered when setting up all-Nordic registry-based cohort studies. Relevant articles describing registries often used for medical research in the Nordic countries were retrieved. Further, our experiences of conducting this type of study, including planning, acquiring permissions, data retrieval and data cleaning and handling, and the possibilities and challenges we have encountered are described. Combining data from the Nordic countries makes it possible to create large and powerful cohorts. The main challenges include obtaining all permissions within each country, usually in the local language, and retrieving the data. These challenges emphasise the importance of having experienced collaborators within each country. Following the acquisition of data, data management requires the understanding of the differences between the variables to be used in the various countries. A concern is the long time required between initiation and completion. Nationwide Nordic registries can be combined into cohorts with high validity and statistical power, but the considerable expertise, workload and time required to complete such cohorts should not be underestimated.

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.

The Long-Term Effects of Organophosphates Poisoning as a Risk Factor of CVDs: A Nationwide Population-Based Cohort Study

PubMed Central

Lin, Cheng-Li; Chang, Shih-Yu; Sung, Fung-Chang; Tai, Sally C. W.

2015-01-01

Background Organophosphorus pesticides are widely used throughout the world. Because of their ease of availability, organophosphorus compounds are commonly used for self-poisoning in developing countries. The acute effects of exposure to organophosphorus pesticides are well known, but the chronic effects are unclear. Recent studies suggest that abnormalities of the central and peripheral nervous systems persisted for up to 5 years after acute poisoning due to a single large dose of organophosphates (OPs). However, the long-term effects on cardiovascular diseases are poorly understood. Methodology/Principal Findings An OPs-exposed cohort (N = 7,561) and an age- and gender-matched control cohort (N = 30,244), both identified from the National Health Insurance Research Database, were compared. We utilized the multivariable Cox proportional model to estimate the risks of developing arrhythmia, coronary artery disease (CAD) and congestive heart failure (CHF). The patients with acute poisoning from OPs had higher incidence rates of arrhythmia (5.89 vs. 3.61 per 1,000 person-years), CAD (9.10 vs. 6.88 per 1,000 person-years), and CHF (3.89 vs. 2.98 per 1,000 person-years) compared with that of the non-OPs poisoning cohort, with a crude subhazard ratio (SHR) of 1.40, 1.13, and 1.12, respectively. Additionally, a significantly higher risk of arrhythmia was observed in the OPs poisoning cohort (adjusted SHR = 1.25) compared with the non-OPs poisoning cohort, particularly in male patients (adjusted SHR = 1.33) and those under 49 years of age (adjusted SHR = 3.16). After accounting for the competing risks of death, there was a higher risk of arrhythmia and CAD during a three year follow-up period (adjusted SHR = 1.50 for arrhythmia; adjusted SHR = 1.10 for CAD). We also found an adjusted SHR of 1.36 associated with developing CHF after 6 years of follow-up for OPs poisoning cohort. Conclusions Acute OPs poisoning may continuously impact human health through mechanisms that are unclear. Any supportive measurements that could contribute to a reduction in the risk of heart disease may be beneficial in cases of OPs poisoning survivors. PMID:26339906

The economic burden of end-of-life care in metastatic breast cancer.

PubMed

Bramley, Thomas; Antao, Vincent; Lunacsek, Orsolya; Hennenfent, Kristin; Masaquel, Anthony

2016-11-01

To assess end-of-life (EOL) total healthcare costs and resource utilization during the last 6 months of claims follow-up among patients with metastatic breast cancer (MBC) who received systemic anti-neoplastic therapy. Newly diagnosed females with MBC initiating treatment January 1, 2003-June 30, 2011 were identified in a large commercial claims database. Two cohorts were defined based on a proxy measure for EOL 1 month prior to the end of last recorded follow-up within the study period: patients who were assumed dead at end of claims follow-up (EOL cohort) and patients who were alive (no-end-of-life [NEOL] cohort). Proxy measures for EOL were obtained from published literature and clinical expert opinion. Cost and resource utilization were evaluated for the 6 months prior to end of claims follow-up. Baseline variables, resource utilization, and costs were compared between cohorts with univariate statistical tests. Adjusted relative risks were calculated for resource utilization measures. A covariate-adjusted generalized linear model evaluated 6-month total healthcare costs. Of the 3,878 females included, 18.5% (n = 718) met the criteria for EOL. Mean observational time (MBC onset to end of claims follow-up) was shorter for the EOL cohort (EOL, 32 months vs NEOL, 35 months; p < 0.001). In adjusted analyses, the EOL cohort had 4.15 times higher 6-month total healthcare costs (EOL, $72,112 vs NEOL, $17,137; p < 0.001). NEOL month-to-month mean total healthcare costs fluctuated between $2336-$3145, while EOL costs increased steadily from $8,956 in the sixth month prior to death to $19,326 in the last month of life. The adjusted relative risk of inpatient, hospice and emergency department utilization was >2 times higher in the EOL cohort (p < 0.001). Potential EOL presented a greater economic burden in the 6 months prior to death. EOL month-to-month costs increased precipitously in the last 2 months of life and were driven by acute inpatient care.

Match or mismatch: the influence of phenology on size-dependent life history and divergence in population structure

USGS Publications Warehouse

Borcherding, Jost; Beeck, Peter; DeAngelis, Donald L.; Scharf, Werner R.

2010-01-01

Summary 1. In gape-limited predators, body size asymmetries determine the outcome of predator-prey interactions. Due to ontogenetic changes in body size, the intensity of intra- and interspecific interactions may change rapidly between the match situation of a predator-prey system and the mismatch situation in which competition, including competition with the prey, dominates. 2. Based on a physiologically structured population model using the European perch (Perca fluviatilis), analysis was performed on how prey density (bream, Abramis brama), initial size differences in the young-of-the-year (YOY) age cohort of the predator, and phenology (time-gap in hatching of predator and prey) influence the size structure of the predator cohort. 3. In relation to the seasonality of reproduction, the match situation of the predator-prey system occurred when perch hatched earlier than bream and when no gape-size limitations existed, leading to decreased size divergence in the predator age cohort. Decreased size divergence was also found when bream hatched much earlier than perch, preventing perch predation on bream occurring, which, in turn, increased the competitive interaction of the perch with bream for the common prey, zooplankton; i.e. the mismatch situation in which also the mean size of the age cohort of the predator decreased. 4. In between the total match and the mismatch, however, only the largest individuals of the perch age cohort were able to prey on the bream, while smaller conspecifics got trapped in competition with each other and with bream for zooplankton, leading to enlarged differences in growth that increased size divergence. 5. The modelling results were combined with 7 years of field data in a lake, where large differences in the length-frequency distribution of YOY perch were observed after their first summer. These field data corroborate that phenology and prey density per predator are important mechanisms in determining size differences within the YOY age cohort of the predator. 6. The results demonstrate that the switch between competitive interactions and a predator-prey relationship depended on phenology. This resulted in pronounced size differences in the YOY age cohort, which had far-reaching consequences for the entire predator population.

Comparison of non-invasive MRI measurements of cerebral blood flow in a large multisite cohort.

PubMed

Dolui, Sudipto; Wang, Ze; Wang, Danny Jj; Mattay, Raghav; Finkel, Mack; Elliott, Mark; Desiderio, Lisa; Inglis, Ben; Mueller, Bryon; Stafford, Randall B; Launer, Lenore J; Jacobs, David R; Bryan, R Nick; Detre, John A

2016-07-01

Arterial spin labeling and phase contrast magnetic resonance imaging provide independent non-invasive methods for measuring cerebral blood flow. We compared global cerebral blood flow measurements obtained using pseudo-continuous arterial spin labeling and phase contrast in 436 middle-aged subjects acquired at two sites in the NHLBI CARDIA multisite study. Cerebral blood flow measured by phase contrast (CBFPC: 55.76 ± 12.05 ml/100 g/min) was systematically higher (p < 0.001) and more variable than cerebral blood flow measured by pseudo-continuous arterial spin labeling (CBFPCASL: 47.70 ± 9.75). The correlation between global cerebral blood flow values obtained from the two modalities was 0.59 (p < 0.001), explaining less than half of the observed variance in cerebral blood flow estimates. Well-established correlations of global cerebral blood flow with age and sex were similarly observed in both CBFPCASL and CBFPC CBFPC also demonstrated statistically significant site differences, whereas no such differences were observed in CBFPCASL No consistent velocity-dependent effects on pseudo-continuous arterial spin labeling were observed, suggesting that pseudo-continuous labeling efficiency does not vary substantially across typical adult carotid and vertebral velocities, as has previously been suggested. Although CBFPCASL and CBFPC values show substantial similarity across the entire cohort, these data do not support calibration of CBFPCASL using CBFPC in individual subjects. The wide-ranging cerebral blood flow values obtained by both methods suggest that cerebral blood flow values are highly variable in the general population. © The Author(s) 2016.

Processed and unprocessed red meat consumption and hypertension in women.

PubMed

Lajous, Martin; Bijon, Anne; Fagherazzi, Guy; Rossignol, Emilie; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise

2014-09-01

High processed red meat consumption is associated with increased risk of cardiovascular disease. The high sodium content of processed red meat could increase blood pressure and explain the association with cardiovascular disease. We evaluated the relation between the consumption of unprocessed and processed red meat and incident hypertension. In a prospective cohort of 44,616 disease-free French women who responded to a validated dietary questionnaire, we observed 10,256 incident cases of hypertension between 1993 and 2008. Cases were identified through self-reports of diagnosed or treated hypertension. Multivariate Cox regression models were adjusted for age, education, smoking, physical activity, body mass index, menopause, menopausal hormone therapy, and alcohol, bread, coffee, and fruit and vegetable consumption. Women who consumed ≥5 servings of processed red meat/wk (50 g = 1 serving) had a 17% higher rate of hypertension than that of women who consumed <1 serving/wk (HR: 1.17; 95% CI: 1.09, 1.26; P-trend = 0.0002). No association was observed between unprocessed red meat consumption and hypertension. When women who consumed ≥5 servings of unprocessed red meat/wk (100 g = 1 serving) were compared with women who consumed <1 serving unprocessed red meat/wk, the multivariate HR was 0.99 (95% CI: 0.91, 1.08; P-trend = 0.63). In this large prospective cohort of French women, we observed an association between the consumption of processed red meat and hypertension. We observed no association for unprocessed red meat consumption and hypertension. © 2014 American Society for Nutrition.

Increased Prevalence of Controlled Viremia and Decreased Rates of HIV Drug Resistance Among HIV-Positive People Who Use Illicit Drugs During a Community-wide Treatment-as-Prevention Initiative.

PubMed

Milloy, M-J; Wood, Evan; Kerr, Thomas; Hogg, Bob; Guillemi, Silvia; Harrigan, P Richard; Montaner, Julio

2016-03-01

Although treatment-as prevention (TasP) is a new cornerstone of global human immunodeficiency virus (HIV)-AIDS strategies, its effect among HIV-positive people who use illicit drugs (PWUD) has yet to be evaluated. We sought to describe longitudinal trends in exposure to antiretroviral therapy (ART), plasma HIV-1 RNA viral load (VL) and HIV drug resistance during a community-wide TasP intervention. We used data from the AIDS Care Cohort to Evaluate Exposure to Survival Services study, a prospective cohort of HIV-positive PWUD linked to HIV clinical monitoring records. We estimated longitudinal changes in the proportion of individuals with VL <50 copies/mL and rates of HIV drug resistance using generalized estimating equations (GEE) and extended Cox models. Between 1 January 2006 and 30 June 2014, 819 individuals were recruited and contributed 1 or more VL observation. During that time, the proportion of individuals with nondetectable VL increased from 28% to 63% (P < .001). In a multivariable GEE model, later year of observation was independently and positively associated with greater likelihood of nondetectable VL (adjusted odds ratio = 1.20 per year; P < .001). Although the proportion of individuals on ART increased, the incidence of HIV drug resistance declined (adjusted hazard ratio = 0.78 per year; P = .011). We observed significant improvements in several measures of exposure to ART and virologic status, including declines in HIV drug resistance, in this large long-running community-recruited cohort of HIV-seropositive illicit drug users during a community-wide ART expansion intervention. Our findings support continued efforts to scale up ART coverage among HIV-positive PWUD. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

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.

Prevalence of atopic dermatitis in infants by domestic water hardness and season of birth: Cohort study.

PubMed

Engebretsen, Kristiane A; Bager, Peter; Wohlfahrt, Jan; Skov, Lone; Zachariae, Claus; Nybo Andersen, Anne-Marie; Melbye, Mads; Thyssen, Jacob P

2017-05-01

Atopic dermatitis (AD) appears to be more common in regions with hard domestic water and in children with a fall/winter birth. However, it is unknown whether a synergistic effect exists. We sought to evaluate the association between domestic water hardness and season of birth, respectively, with onset of AD within the first 18 months of life in a large Danish birth cohort. Of children from the Danish National Birth Cohort, 52,950 were included. History of physician-diagnosed AD and population characteristics were obtained from interviews. Birth data were obtained from the Civil Registration System, and domestic water hardness data were obtained from the Geological Survey of Denmark and Greenland. The relative prevalence (RP) of AD was calculated by using log-linear binomial regression. The prevalence of AD was 15.0% (7,942/52,950). The RP of AD was 5% (RP trend , 1.05; 95% CI, 1.03-1.07) higher for each 5° increase in domestic water hardness (range, 6.60-35.90 German degrees of hardness [118-641 mg/L]). Although the RP of AD was higher in children with a fall (RP, 1.24; 95% CI, 1.17-1.31) or winter (RP, 1.18; 95% CI, 1.11-1.25) birth, no significant interaction was observed with domestic water hardness. The population attributable risk of hard domestic water on AD was 2%. We observed that early exposure to hard domestic water and a fall/winter birth was associated with an increase in the relative prevalence of AD within the first 18 months of life. Although the 2 exposures did not interact synergistically, a dose-response relationship was observed between domestic water hardness and AD. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Are Math Grades Cyclical?

ERIC Educational Resources Information Center

Adams, Gerald J.; Dial, Micah

1998-01-01

The cyclical nature of mathematics grades was studied for a cohort of elementary school students from a large metropolitan school district in Texas over six years (average cohort size of 8495). The study used an autoregressive integrated moving average (ARIMA) model. Results indicate that grades do exhibit a significant cyclical pattern. (SLD)

Genetic parameters for hoof health traits estimated with linear and threshold models using alternative cohorts.

PubMed

Malchiodi, F; Koeck, A; Mason, S; Christen, A M; Kelton, D F; Schenkel, F S; Miglior, F

2017-04-01

A national genetic evaluation program for hoof health could be achieved by using hoof lesion data collected directly by hoof trimmers. However, not all cows in the herds during the trimming period are always presented to the hoof trimmer. This preselection process may not be completely random, leading to erroneous estimations of the prevalence of hoof lesions in the herd and inaccuracies in the genetic evaluation. The main objective of this study was to estimate genetic parameters for individual hoof lesions in Canadian Holsteins by using an alternative cohort to consider all cows in the herd during the period of the hoof trimming sessions, including those that were not examined by the trimmer over the entire lactation. A second objective was to compare the estimated heritabilities and breeding values for resistance to hoof lesions obtained with threshold and linear models. Data were recorded by 23 hoof trimmers serving 521 herds located in Alberta, British Columbia, and Ontario. A total of 73,559 hoof-trimming records from 53,654 cows were collected between 2009 and 2012. Hoof lesions included in the analysis were digital dermatitis, interdigital dermatitis, interdigital hyperplasia, sole hemorrhage, sole ulcer, toe ulcer, and white line disease. All variables were analyzed as binary traits, as the presence or the absence of the lesions, using a threshold and a linear animal model. Two different cohorts were created: Cohort 1, which included only cows presented to hoof trimmers, and Cohort 2, which included all cows present in the herd at the time of hoof trimmer visit. Using a threshold model, heritabilities on the observed scale ranged from 0.01 to 0.08 for Cohort 1 and from 0.01 to 0.06 for Cohort 2. Heritabilities estimated with the linear model ranged from 0.01 to 0.07 for Cohort 1 and from 0.01 to 0.05 for Cohort 2. Despite a low heritability, the distribution of the sire breeding values showed large and exploitable variation among sires. Higher breeding values for hoof lesion resistance corresponded to sires with a higher prevalence of healthy daughters. The rank correlations between estimated breeding values ranged from 0.96 to 0.99 when predicted using either one of the 2 cohorts and from 0.94 to 0.99 when predicted using either a threshold or a linear model. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Impact of Adalimumab on Work Productivity and Activity Impairment in Japanese Patients with Rheumatoid Arthritis: Large-Scale, Prospective, Single-Cohort ANOUVEAU Study.

PubMed

Takeuchi, Tsutomu; Nakajima, Ryo; Komatsu, Shuichi; Yamazaki, Kiyotaka; Nakamura, Tomohiro; Agata, Naoki; Igarashi, Ataru; Tango, Toshiro; Tanaka, Yoshiya

2017-03-01

The Adalimumab Non-interventional Trial for Up-verified Effects and Utility (ANOUVEAU) was a large-scale, multicenter, prospective, observational, single-cohort study that evaluated the effects of adalimumab (ADA) on rheumatoid arthritis (RA)-related work productivity and activity impairment (RA-related WPAI) and disease activity in routine rheumatology care in Japan. Patients with RA were categorized as paid workers (PWs, ≥35 h/week), part-time workers (PTWs, <35 h/week), or homemakers (HMs, unemployed) and were administered the WPAI for RA (WPAI/RA) questionnaire. All patients who received ADA were followed for 48 weeks to evaluate safety and effectiveness. Of the 1808 patients analyzed, 825, 243, and 740 patients were PWs, PTWs, and HMs, respectively. WPAI/RA domain scores significantly improved at weeks 12, 24, and 48 in all groups, with maximum improvement observed for PWs (p < 0.05). Additionally, remission rates (according to Disease Activity Score 28, erythrocyte sedimentation rate, Simplified Disease Activity Index, or Health Assessment Questionnaire-Disability Index scores) and EuroQol 5-Dimension 3-Level scores significantly increased from baseline to 48 weeks in all groups (p < 0.0001). Analysis of patient subgroups revealed better WPAI/RA outcomes for patients who were biologic-naïve, treated with concomitant methotrexate, or with RA duration of ≤2 years (p < 0.05). The rate of serious adverse events over 48 weeks of ADA treatment was 5.23%. Treatment with ADA provided sustained improvement in WPAI and had an acceptable safety profile in patients with RA. AbbVie GK and Eisai Co., Ltd. ClinicalTrials.gov identifier, NCT01346488.

Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy.

PubMed

Fallil, Zianka; Pardoe, Heath; Bachman, Robert; Cunningham, Benjamin; Parulkar, Isha; Shain, Catherine; Poduri, Annapurna; Knowlton, Robert; Kuzniecky, Ruben

2015-10-01

Periventricular nodular heterotopia (PVNH) is a malformation of cortical development due to impaired neuronal migration resulting in the formation of nodular masses of neurons and glial cells in close proximity to the ventricular walls. We report the clinical characteristics of the largest case series of FLNA-negative patients with seizures and bilateral periventricular heterotopia. Participants were recruited through the Epilepsy Phenome/Genome Project (EPGP), a multicenter collaborative effort to collect detailed phenotypic data and DNA on a large number of individuals with epilepsy, including a cohort with symptomatic epilepsy related to PVNH. Included subjects had epilepsy, and MRI confirmed bilateral PVNH. Magnetic resonance imaging studies were visually and quantitatively reviewed to investigate the topographic extent of PVNH, symmetry, and laterality. We analyzed data on 71 patients with bilateral PVNH. The incidence of febrile seizures was 16.6%. There was at least one other family member with epilepsy in 36.9% of this population. Developmental delay was present in 21.8%. Focal onset seizures were the most common type of seizure presentation (79.3%). High heterotopia burden was strongly associated with female gender and trigonal nodular localization. There was no evidence for differences in brain volume between PVNH subjects and controls. No relationship was observed between heterotopic volume and gender, developmental delay, location of PVNH, ventricular or cerebellar abnormalities, laterality of seizure onset, age at seizure onset, and duration of epilepsy. A direct correlation was observed between high heterotopia burden, female gender, and trigonal location in this large cohort of FLNA-negative bilateral PVNH patients with epilepsy. Quantitative MRI measurements indicated that this correlation is based on the diffuse nature of the heterotopic nodules rather than on the total volume of abnormal heterotopic tissue. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical progression and metachronous paragangliomas in a large cohort of SDHD germline variant carriers.

PubMed

Heesterman, Berdine L; de Pont, Lisa M H; van der Mey, Andel Gl; Bayley, Jean-Pierre; Corssmit, Eleonora Pm; Hes, Frederik J; Verbist, Berit M; van Benthem, Peter Paul G; Jansen, Jeroen C

2018-05-18

Although it is well established that paternally transmitted germline variants in SDHD are associated with multifocal paragangliomas and lifelong follow-up is generally advised, the risk of metachronous lesions is presently unknown. In a large Dutch cohort of SDHD variant carriers, we studied the development of new paragangliomas, and the evolution of symptoms and cranial nerve impairment. Recurrent event analysis and the Kaplan-Meier product limit estimator were used to study the risk of new lesions. The relation between several predictors and development of new symptoms was assessed using logistic regression. Of the 222 SDHD variant carriers included, 65% presented with symptoms and 11% with cranial nerve dysfunction. Over a median period of 8 years, 42% reported new symptoms, and new cranial nerve impairment was observed in 11% of subjects. The estimated fraction of subjects that developed new HNPGL increased to 73% (95% CI: 52-85%) after 22 years of follow-up. Males were more likely to develop new HNPGL compared to females (HR: 1.63, 95% CI: 1.10-2.40), as were subjects that presented with symptoms, compared to subjects that were asymptomatic at baseline (HR: 1.61, 95% CI: 1.01-2.55). In addition, the risk of new lesions decreased with number of HNPGL present at first diagnosis (HR: 0.68 and 95% CI: 0.56-0.82). Carriers of a paternally inherited SDHD variant face a considerable risk for new HNPGL. In addition, nearly 50% of subjects reported new symptoms. However, new cranial nerve deficits were observed in only 11%, which is less than reported in surgical series. These risks should be taken into account when considering treatment strategies and counseling.

Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer.

PubMed

Couch, Fergus J; Hart, Steven N; Sharma, Priyanka; Toland, Amanda Ewart; Wang, Xianshu; Miron, Penelope; Olson, Janet E; Godwin, Andrew K; Pankratz, V Shane; Olswold, Curtis; Slettedahl, Seth; Hallberg, Emily; Guidugli, Lucia; Davila, Jaime I; Beckmann, Matthias W; Janni, Wolfgang; Rack, Brigitte; Ekici, Arif B; Slamon, Dennis J; Konstantopoulou, Irene; Fostira, Florentia; Vratimos, Athanassios; Fountzilas, George; Pelttari, Liisa M; Tapper, William J; Durcan, Lorraine; Cross, Simon S; Pilarski, Robert; Shapiro, Charles L; Klemp, Jennifer; Yao, Song; Garber, Judy; Cox, Angela; Brauch, Hiltrud; Ambrosone, Christine; Nevanlinna, Heli; Yannoukakos, Drakoulis; Slager, Susan L; Vachon, Celine M; Eccles, Diana M; Fasching, Peter A

2015-02-01

Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing of patients. We assessed the frequency of mutations in 17 predisposition genes, including BRCA1 and BRCA2, in a large cohort of patients with triple-negative breast cancer (TNBC) unselected for family history of breast or ovarian cancer to determine the utility of germline genetic testing for those with TNBC. Patients with TNBC (N = 1,824) unselected for family history of breast or ovarian cancer were recruited through 12 studies, and germline DNA was sequenced to identify mutations. Deleterious mutations were identified in 14.6% of all patients. Of these, 11.2% had mutations in the BRCA1 (8.5%) and BRCA2 (2.7%) genes. Deleterious mutations in 15 other predisposition genes were detected in 3.7% of patients, with the majority observed in genes involved in homologous recombination, including PALB2 (1.2%) and BARD1, RAD51D, RAD51C, and BRIP1 (0.3% to 0.5%). Patients with TNBC with mutations were diagnosed at an earlier age (P < .001) and had higher-grade tumors (P = .01) than those without mutations. Deleterious mutations in predisposition genes are present at high frequency in patients with TNBC unselected for family history of cancer. Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCA2. Although mutations in other predisposition genes are observed among patients with TNBC, better cancer risk estimates are needed before these mutations are used for clinical risk assessment in relatives. © 2014 by American Society of Clinical Oncology.

Inherited Mutations in 17 Breast Cancer Susceptibility Genes Among a Large Triple-Negative Breast Cancer Cohort Unselected for Family History of Breast Cancer

PubMed Central

Couch, Fergus J.; Hart, Steven N.; Sharma, Priyanka; Toland, Amanda Ewart; Wang, Xianshu; Miron, Penelope; Olson, Janet E.; Godwin, Andrew K.; Pankratz, V. Shane; Olswold, Curtis; Slettedahl, Seth; Hallberg, Emily; Guidugli, Lucia; Davila, Jaime I.; Beckmann, Matthias W.; Janni, Wolfgang; Rack, Brigitte; Ekici, Arif B.; Slamon, Dennis J.; Konstantopoulou, Irene; Fostira, Florentia; Vratimos, Athanassios; Fountzilas, George; Pelttari, Liisa M.; Tapper, William J.; Durcan, Lorraine; Cross, Simon S.; Pilarski, Robert; Shapiro, Charles L.; Klemp, Jennifer; Yao, Song; Garber, Judy; Cox, Angela; Brauch, Hiltrud; Ambrosone, Christine; Nevanlinna, Heli; Yannoukakos, Drakoulis; Slager, Susan L.; Vachon, Celine M.; Eccles, Diana M.; Fasching, Peter A.

2015-01-01

Purpose Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing of patients. We assessed the frequency of mutations in 17 predisposition genes, including BRCA1 and BRCA2, in a large cohort of patients with triple-negative breast cancer (TNBC) unselected for family history of breast or ovarian cancer to determine the utility of germline genetic testing for those with TNBC. Patients and Methods Patients with TNBC (N = 1,824) unselected for family history of breast or ovarian cancer were recruited through 12 studies, and germline DNA was sequenced to identify mutations. Results Deleterious mutations were identified in 14.6% of all patients. Of these, 11.2% had mutations in the BRCA1 (8.5%) and BRCA2 (2.7%) genes. Deleterious mutations in 15 other predisposition genes were detected in 3.7% of patients, with the majority observed in genes involved in homologous recombination, including PALB2 (1.2%) and BARD1, RAD51D, RAD51C, and BRIP1 (0.3% to 0.5%). Patients with TNBC with mutations were diagnosed at an earlier age (P < .001) and had higher-grade tumors (P = .01) than those without mutations. Conclusion Deleterious mutations in predisposition genes are present at high frequency in patients with TNBC unselected for family history of cancer. Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCA2. Although mutations in other predisposition genes are observed among patients with TNBC, better cancer risk estimates are needed before these mutations are used for clinical risk assessment in relatives. PMID:25452441

Inflammation and Arterial Stiffness in Chronic Kidney Disease: Findings From the CRIC Study.

PubMed

Peyster, Eliot; Chen, Jing; Feldman, Harold I; Go, Alan S; Gupta, Jayanta; Mitra, Nandita; Pan, Qiang; Porter, Anna; Rahman, Mahboob; Raj, Dominic; Reilly, Muredach; Wing, Maria R; Yang, Wei; Townsend, Raymond R

2017-04-01

Chronic kidney disease (CKD) and arterial stiffness are associated with increased cardiovascular morbidity and mortality. Inflammation is proposed to have a role in the development of arterial stiffness, and CKD is recognized as a proinflammatory state. Arterial stiffness is increased in CKD, and cross-sectional data has suggested a link between increased inflammatory markers in CKD and higher measures of arterial stiffness. However, no large scale investigations have examined the impact of inflammation on the progression of arterial stiffness in CKD. We performed baseline assessments of 5 inflammatory markers in 3,939 participants from the chronic renal insufficiency cohort (CRIC), along with serial measurements of arterial stiffness at 0, 2, and 4 years of follow-up. A total of 2,933 participants completed each of the follow-up stiffness measures. In cross-sectional analysis at enrollment, significant associations with at least 2 measures of stiffness were observed for fibrinogen, interleukin-6, high-sensitivity C-reactive protein, proteinuria, and composite inflammation score after adjustment for confounders. In longitudinal analyses, there were few meaningful correlations between baseline levels of inflammation and changes in metrics of arterial stiffness over time. In a large cohort of CKD participants, we observed multiple significant correlations between initial markers of inflammation and metrics of arterial stiffness, but baseline inflammation did not predict changes in arterial stiffness over time. While well-described biologic mechanisms provide the basis for our understanding of the cross-sectional results, continued efforts to design longitudinal studies are necessary to fully elucidate the relationship between chronic inflammation and arterial stiffening. © American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Association of Systemic Lupus Erythematosus With Decreased Immunosuppressive Potential of the IgG Glycome

PubMed Central

Vučković, Frano; Krištić, Jasminka; Gudelj, Ivan; Teruel, Maria; Keser, Toma; Pezer, Marija; Pučić‐Baković, Maja; Štambuk, Jerko; Trbojević‐Akmačić, Irena; Barrios, Clara; Pavić, Tamara; Menni, Cristina; Wang, Youxin; Zhou, Yong; Cui, Liufu; Song, Haicheng; Zeng, Qiang; Guo, Xiuhua; Pons‐Estel, Bernardo A.; McKeigue, Paul; Leslie Patrick, Alan; Gornik, Olga; Spector, Tim D.; Harjaček, Miroslav; Molokhia, Mariam; Wang, Wei; Lauc, Gordan

2015-01-01

Objective Glycans attached to the Fc portion of IgG are important modulators of IgG effector functions. Interindividual differences in IgG glycome composition are large and they associate strongly with different inflammatory and autoimmune diseases. IKZF1, HLA–DQ2A/B, and BACH2 genetic loci that affect IgG glycome composition show pleiotropy with systemic lupus erythematosus (SLE), indicating a potentially causative role of aberrant IgG glycosylation in SLE. We undertook this large multicenter case–control study to determine whether SLE is associated with altered IgG glycosylation. Methods Using ultra‐performance liquid chromatography analysis of released glycans, we analyzed the composition of the IgG glycome in 261 SLE patients and 247 matched controls of Latin American Mestizo origin (the discovery cohort) and in 2 independent replication cohorts of different ethnicity (108 SLE patients and 193 controls from Trinidad, and 106 SLE patients and 105 controls from China). Results Multiple statistically significant differences in IgG glycome composition were observed between patients and controls. The most significant changes included decreased galactosylation and sialylation of IgG (which regulate proinflammatory and antiinflammatory actions of IgG) as well as decreased core fucose and increased bisecting N‐acetylglucosamine (which affect antibody‐dependent cell‐mediated cytotoxicity). Conclusion The IgG glycome in SLE patients is significantly altered in a way that decreases immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the intensity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in SLE. PMID:26200652

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.

Observations of a large Dent disease cohort.

PubMed

Blanchard, Anne; Curis, Emmanuel; Guyon-Roger, Tiphaine; Kahila, Diana; Treard, Cyrielle; Baudouin, Véronique; Bérard, Etienne; Champion, Gérard; Cochat, Pierre; Dubourg, Julie; de la Faille, Renaud; Devuyst, Olivier; Deschenes, Georges; Fischbach, Michel; Harambat, Jérôme; Houillier, Pascal; Karras, Alexandre; Knebelmann, Bertrand; Lavocat, Marie-Pierre; Loirat, Chantal; Merieau, Elodie; Niaudet, Patrick; Nobili, François; Novo, Robert; Salomon, Rémi; Ulinski, Tim; Jeunemaître, Xavier; Vargas-Poussou, Rosa

2016-08-01

Dent disease classically combines low-molecular-weight proteinuria, hypercalciuria with nephrocalcinosis, and renal failure. Nephrotic range proteinuria, normal calciuria, and hypokalemia have been rarely reported. It is unknown whether the changes in phenotype observed over time are explained by a decrease in glomerular filtration rate (GFR) or whether there is any phenotype-genotype relationship. To answer this we retrospectively analyzed data from 109 male patients with CLCN5 mutations (Dent-1) and 9 patients with mutation of the OCRL gene (Dent-2). In Dent-1 disease, the estimated GFR decreased with age, by 1.0 to 1.6 ml/min per 1.73 m(2)/yr in the absence and presence of nephrocalcinosis, respectively, with no significant difference. Median values of low-molecular-weight proteinuria were in the nephrotic range and remained at the same level even in late renal disease. End-stage renal disease occurred in 12 patients, at a median age of 40 years. Hypercalciuria decreased with glomerular filtration and was absent in 40% of the patients under 30 and 85% of those over the age of 30. Hypophosphatemia did not resolve with age and calcitriol concentrations were in the upper normal range. Kalemia decreased with age, with half of the patients over the age of 18 presenting with hypokalemia. Thus, no phenotype/genotype correlation was observed in this cohort of patients with Dent disease. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: Findings from a prospective cohort study.

PubMed

Stepien, Magdalena; Duarte-Salles, Talita; Fedirko, Veronika; Floegel, Anne; Barupal, Dinesh Kumar; Rinaldi, Sabina; Achaintre, David; Assi, Nada; Tjønneland, Anne; Overvad, Kim; Bastide, Nadia; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Kühn, Tilman; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Lagiou, Pagona; Saieva, Calogero; Agnoli, Claudia; Panico, Salvatore; Tumino, Rosario; Naccarati, Alessio; Bueno-de-Mesquita, H B As; Peeters, Petra H; Weiderpass, Elisabete; Quirós, J Ramón; Agudo, Antonio; Sánchez, María-José; Dorronsoro, Miren; Gavrila, Diana; Barricarte, Aurelio; Ohlsson, Bodil; Sjöberg, Klas; Werner, Mårten; Sund, Malin; Wareham, Nick; Khaw, Kay-Tee; Travis, Ruth C; Schmidt, Julie A; Gunter, Marc; Cross, Amanda; Vineis, Paolo; Romieu, Isabelle; Scalbert, Augustin; Jenab, Mazda

2016-01-15

Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development. © 2015 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.

[Connecting biobanks of large European cohorts (EU Project BBMRI-LPC)].

PubMed

Kuhn, Klaus A; Bild, Raffael; Anton, Gabriele; Schuffenhauer, Simone; Wichmann, H-Erich

2016-03-01

In addition to the Biobanking and BioMolecular resources Research Initiative (BBMRI), which is establishing a European research infrastructure for biobanks, a network for large European prospective cohorts (LPC) is being built to facilitate transnational research into important groups of diseases and health care. One instrument for this is the database "LPC Catalogue," which supports access to the biomaterials of the participating cohorts. To present the LPC Catalogue as a relevant tool for connecting European biobanks. In addition, the LPC Catalogue has been extended to establish compatibility with existing Minimum Information About Biobank data Sharing (MIABIS) and to allow for more detailed search requests. This article describes the LPC Catalogue, its organizational and technical structure, and the aforementioned extensions. The LPC Catalogue provides a structured overview of the participating LPCs. It offers various retrieval possibilities and a search function. To support more detailed search requests, a new module has been developed, called a "data cube". The provision of data by the cohorts is being supported by a "connector" component. The LPC Catalogue contains data on 22 cohorts and more than 3.8 million biosamples. At present, data on the biosamples of three cohorts have been acquired for the "cube," which is continuously being expanded. In the BBMRI-LPC, tendering for scientific projects using the data and samples of the participating cohorts is currently being carried out. In this context, several proposals have already been approved. The LPC Catalogue is supporting transnational access to biosamples. A comparison with existing solutions illustrates the relevance of its functionality.

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.

Association between long-term exposure to ambient air pollution and diabetes mortality in the US.

PubMed

Lim, Chris C; Hayes, Richard B; Ahn, Jiyoung; Shao, Yongzhao; Silverman, Debra T; Jones, Rena R; Garcia, Cynthia; Thurston, George D

2018-05-17

Recent mechanistic and epidemiological evidence implicates air pollution as a potential risk factor for diabetes; however, mortality risks have not been evaluated in a large US cohort assessing exposures to multiple pollutants with detailed consideration of personal risk factors for diabetes. We assessed the effects of long-term ambient air pollution exposures on diabetes mortality in the NIH-AARP Diet and Health Study, a cohort of approximately a half million subjects across the contiguous U.S. The cohort, with a follow-up period between 1995 and 2011, was linked to residential census tract estimates for annual mean concentration levels of PM 2.5 , NO 2 , and O 3 . Associations between the air pollutants and the risk of diabetes mortality (N = 3598) were evaluated using multivariate Cox proportional hazards models adjusted for both individual-level and census-level contextual covariates. Diabetes mortality was significantly associated with increasing levels of both PM 2.5 (HR = 1.19; 95% CI: 1.03-1.39 per 10 μg/m 3 ) and NO 2 (HR = 1.09; 95% CI: 1.01-1.18 per 10 ppb). The strength of the relationship was robust to alternate exposure assessments and model specifications. We also observed significant effect modification, with elevated mortality risks observed among those with higher BMI and lower levels of fruit consumption. We found that long-term exposure to PM 2.5 and NO 2 , but not O 3 , is related to increased risk of diabetes mortality in the U.S, with attenuation of adverse effects by lower BMI and higher fruit consumption, suggesting that air pollution is involved in the etiology and/or control of diabetes. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Severe Hypoglycemia Requiring Medical Intervention in a Large Cohort of Adults With Diabetes Receiving Care in U.S. Integrated Health Care Delivery Systems: 2005-2011.

PubMed

Pathak, Ram D; Schroeder, Emily B; Seaquist, Elizabeth R; Zeng, Chan; Lafata, Jennifer Elston; Thomas, Abraham; Desai, Jay; Waitzfelder, Beth; Nichols, Gregory A; Lawrence, Jean M; Karter, Andrew J; Steiner, John F; Segal, Jodi; O'Connor, Patrick J

2016-03-01

Appropriate glycemic control is fundamental to diabetes care, but aggressive glucose targets and intensive therapy may unintentionally increase episodes of hypoglycemia. We quantified the burden of severe hypoglycemia requiring medical intervention in a well-defined population of insured individuals with diabetes receiving care in integrated health care delivery systems across the U.S. This observational cohort study included 917,440 adults with diabetes receiving care during 2005 to 2011 at participating SUrveillance, PREvention, and ManagEment of Diabetes Mellitus (SUPREME-DM) network sites. Severe hypoglycemia rates were based on any occurrence of hypoglycemia-related ICD-9 codes from emergency department or inpatient medical encounters and reported overall and by age, sex, comorbidity status, antecedent A1C level, and medication use. Annual rates of severe hypoglycemia ranged from 1.4 to 1.6 events per 100 person-years. Rates of severe hypoglycemia were higher among those with older age, chronic kidney disease, congestive heart failure, cardiovascular disease, depression, and higher A1C levels, and in users of insulin, insulin secretagogues, or β-blockers (P < 0.001 for all). Changes in severe hypoglycemia occurrence over time were not clinically significant in the cohort as a whole but were observed in subgroups of individuals with chronic kidney disease, congestive heart failure, and cardiovascular disease. Risk of severe hypoglycemia in clinical settings is considerably higher in identifiable patient subgroups than in randomized controlled trials. Strategies that reduce the risk of hypoglycemia in high-risk patients are needed. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

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.

Combined effect of blood pressure and total cholesterol levels on long-term risks of subtypes of cardiovascular death: Evidence for Cardiovascular Prevention from Observational Cohorts in Japan.

PubMed

Satoh, Michihiro; Ohkubo, Takayoshi; Asayama, Kei; Murakami, Yoshitaka; Sakurai, Masaru; Nakagawa, Hideaki; Iso, Hiroyasu; Okayama, Akira; Miura, Katsuyuki; Imai, Yutaka; Ueshima, Hirotsugu; Okamura, Tomonori

2015-03-01

No large-scale, longitudinal studies have examined the combined effects of blood pressure (BP) and total cholesterol levels on long-term risks for subtypes of cardiovascular death in an Asian population. To investigate these relationships, a meta-analysis of individual participant data, which included 73 916 Japanese subjects (age, 57.7 years; men, 41.1%) from 11 cohorts, was conducted. During a mean follow-up of 15.0 years, deaths from coronary heart disease, ischemic stroke, and intraparenchymal hemorrhage occurred in 770, 724, and 345 cases, respectively. Cohort-stratified Cox proportional hazard models were used. After stratifying the participants by 4 systolic BP ×4 total cholesterol categories, the group with systolic BP ≥160 mm Hg with total cholesterol ≥5.7 mmol/L had the greatest risk for coronary heart disease death (adjusted hazard ratio, 4.39; P<0.0001 versus group with systolic BP <120 mm Hg and total cholesterol <4.7 mmol/L). The adjusted hazard ratios of systolic BP (per 20 mm Hg) increased with increases in total cholesterol categories (hazard ratio, 1.52; P<0.0001 in group with total cholesterol ≥5.7 mmol/L). Similarly, the adjusted hazard ratios of total cholesterol increased with increases in systolic BP categories (P for interaction ≤0.04). Systolic BP was positively associated with ischemic stroke and intraparenchymal hemorrhage death, and total cholesterol was inversely associated with intraparenchymal hemorrhage, but no significant interactions between BP and total cholesterol were observed for stroke. High BP and high total cholesterol can synergistically increase the risk for coronary heart disease death but not for stroke in the Asian population. © 2015 American Heart Association, Inc.

Young driver education programs that build resilience have potential to reduce road crashes.

PubMed

Senserrick, Teresa; Ivers, Rebecca; Boufous, Soufiane; Chen, Huei-Yang; Norton, Robyn; Stevenson, Mark; van Beurden, Eric; Zask, Avigdor

2009-11-01

The research aimed to explore associations between participation in 2 education programs for school-based learner drivers and subsequent road traffic offenses and crashes among a large cohort of newly licensed drivers. DRIVE is a prospective cohort study of 20822 first-year drivers aged 17 to 24 in New South Wales (NSW), Australia. Participants completed a detailed questionnaire and consented to data linkage in 2003-2004. Questionnaire items included year of participation in 2 specific education programs: a 1-day workshop-only program focusing on driving risks ("driver-focused") and a whole-of-community program also including a 1-day workshop but also longer term follow-up activities and a broader focus on reducing risk-taking and building resilience ("resilience-focused"). Survey data were subsequently linked to police-reported crash and offense data for 1996-2005. Poisson regression models that adjusted for multiple confounders were created to explore offenses and crashes as a driver (dichotomized as 0 vs >or=1) after program participation. Offenses did not differ between groups; however, whereas the driver-focused program was not associated with reduced crash risk, the resilience-focused program was associated with a 44% reduced relative risk for crash (0.56 [95% confidence interval: 0.34-0.93]). The large effect size observed and complementary findings from a comparable randomized, controlled trial in the United States suggest programs that focus more generally on reducing risks and building resilience have the potential to reduce crashes. A large, representative, randomized, controlled trial is urgently needed to confirm road safety benefits and ensure evidence-based spending and practitioner recommendations in this field.

The Association of Hot Red Chili Pepper Consumption and Mortality: A Large Population-Based Cohort Study

PubMed Central

Chopan, Mustafa

2017-01-01

The evidence base for the health effects of spice consumption is insufficient, with only one large population-based study and no reports from Europe or North America. Our objective was to analyze the association between consumption of hot red chili peppers and mortality, using a population-based prospective cohort from the National Health and Nutritional Examination Survey (NHANES) III, a representative sample of US noninstitutionalized adults, in which participants were surveyed from 1988 to 1994. The frequency of hot red chili pepper consumption was measured in 16,179 participants at least 18 years of age. Total and cause-specific mortality were the main outcome measures. During 273,877 person-years of follow-up (median 18.9 years), a total of 4,946 deaths were observed. Total mortality for participants who consumed hot red chili peppers was 21.6% compared to 33.6% for those who did not (absolute risk reduction of 12%; relative risk of 0.64). Adjusted for demographic, lifestyle, and clinical characteristics, the hazard ratio was 0.87 (P = 0.01; 95% Confidence Interval 0.77, 0.97). Consumption of hot red chili peppers was associated with a 13% reduction in the instantaneous hazard of death. Similar, but statistically nonsignificant trends were seen for deaths from vascular disease, but not from other causes. In this large population-based prospective study, the consumption of hot red chili pepper was associated with reduced mortality. Hot red chili peppers may be a beneficial component of the diet. PMID:28068423

Assessment of large copy number variants in patients with apparently isolated congenital left-sided cardiac lesions reveals clinically relevant genomic events.

PubMed

Hanchard, Neil A; Umana, Luis A; D'Alessandro, Lisa; Azamian, Mahshid; Poopola, Mojisola; Morris, Shaine A; Fernbach, Susan; Lalani, Seema R; Towbin, Jeffrey A; Zender, Gloria A; Fitzgerald-Butt, Sara; Garg, Vidu; Bowman, Jessica; Zapata, Gladys; Hernandez, Patricia; Arrington, Cammon B; Furthner, Dieter; Prakash, Siddharth K; Bowles, Neil E; McBride, Kim L; Belmont, John W

2017-08-01

Congenital left-sided cardiac lesions (LSLs) are a significant contributor to the mortality and morbidity of congenital heart disease (CHD). Structural copy number variants (CNVs) have been implicated in LSL without extra-cardiac features; however, non-penetrance and variable expressivity have created uncertainty over the use of CNV analyses in such patients. High-density SNP microarray genotyping data were used to infer large, likely-pathogenic, autosomal CNVs in a cohort of 1,139 probands with LSL and their families. CNVs were molecularly confirmed and the medical records of individual carriers reviewed. The gene content of novel CNVs was then compared with public CNV data from CHD patients. Large CNVs (>1 MB) were observed in 33 probands (∼3%). Six of these were de novo and 14 were not observed in the only available parent sample. Associated cardiac phenotypes spanned a broad spectrum without clear predilection. Candidate CNVs were largely non-recurrent, associated with heterozygous loss of copy number, and overlapped known CHD genomic regions. Novel CNV regions were enriched for cardiac development genes, including seven that have not been previously associated with human CHD. CNV analysis can be a clinically useful and molecularly informative tool in LSLs without obvious extra-cardiac defects, and may identify a clinically relevant genomic disorder in a small but important proportion of these individuals. © 2017 Wiley Periodicals, Inc.

A Naive Bayes machine learning approach to risk prediction using censored, time-to-event data.

PubMed

Wolfson, Julian; Bandyopadhyay, Sunayan; Elidrisi, Mohamed; Vazquez-Benitez, Gabriela; Vock, David M; Musgrove, Donald; Adomavicius, Gediminas; Johnson, Paul E; O'Connor, Patrick J

2015-09-20

Predicting an individual's risk of experiencing a future clinical outcome is a statistical task with important consequences for both practicing clinicians and public health experts. Modern observational databases such as electronic health records provide an alternative to the longitudinal cohort studies traditionally used to construct risk models, bringing with them both opportunities and challenges. Large sample sizes and detailed covariate histories enable the use of sophisticated machine learning techniques to uncover complex associations and interactions, but observational databases are often 'messy', with high levels of missing data and incomplete patient follow-up. In this paper, we propose an adaptation of the well-known Naive Bayes machine learning approach to time-to-event outcomes subject to censoring. We compare the predictive performance of our method with the Cox proportional hazards model which is commonly used for risk prediction in healthcare populations, and illustrate its application to prediction of cardiovascular risk using an electronic health record dataset from a large Midwest integrated healthcare system. Copyright © 2015 John Wiley & Sons, Ltd.

Association between Exposure of Young Children to Procedures Requiring General Anesthesia and Learning and Behavioral Outcomes in a Population-based Birth Cohort.

PubMed

Hu, Danqing; Flick, Randall P; Zaccariello, Michael J; Colligan, Robert C; Katusic, Slavica K; Schroeder, Darrell R; Hanson, Andrew C; Buenvenida, Shonie L; Gleich, Stephen J; Wilder, Robert T; Sprung, Juraj; Warner, David O

2017-08-01

Exposure of young animals to general anesthesia causes neurodegeneration and lasting behavioral abnormalities; whether these findings translate to children remains unclear. This study used a population-based birth cohort to test the hypothesis that multiple, but not single, exposures to procedures requiring general anesthesia before age 3 yr are associated with adverse neurodevelopmental outcomes. A retrospective study cohort was assembled from children born in Olmsted County, Minnesota, from 1996 to 2000 (inclusive). Propensity matching selected children exposed and not exposed to general anesthesia before age 3 yr. Outcomes ascertained via medical and school records included learning disabilities, attention-deficit/hyperactivity disorder, and group-administered ability and achievement tests. Analysis methods included proportional hazard regression models and mixed linear models. For the 116 multiply exposed, 457 singly exposed, and 463 unexposed children analyzed, multiple, but not single, exposures were associated with an increased frequency of both learning disabilities and attention-deficit/hyperactivity disorder (hazard ratio for learning disabilities = 2.17 [95% CI, 1.32 to 3.59], unexposed as reference). Multiple exposures were associated with decreases in both cognitive ability and academic achievement. Single exposures were associated with modest decreases in reading and language achievement but not cognitive ability. These findings in children anesthetized with modern techniques largely confirm those found in an older birth cohort and provide additional evidence that children with multiple exposures are more likely to develop adverse outcomes related to learning and attention. Although a robust association was observed, these data do not determine whether anesthesia per se is causal.

Radiographic and Clinical Outcomes of the Treatment of Immature Permanent Teeth by Revascularization or Apexification: A Pilot Retrospective Cohort Study

PubMed Central

Alobaid, Adel S.; Cortes, Lina M.; Lo, Jeffery; Nguyen, Thuan T.; Albert, Jeffery; Abu-Melha, Abdulaziz S; Lin, Louis M.; Gibbs, Jennifer L.

2014-01-01

Introduction This retrospective cohort study compared clinical and radiographic outcomes of endodontic treatment performed in immature non-vital permanent teeth, by apexification (calcium hydroxide or apical barrier with Mineral Trioxide Aggregate (MTA)), versus revascularization. Methods A comprehensive chart review was performed to obtain a cohort of sequential previously completed cases with recalls. Clinical and radiographic data were collected for 31 treated teeth (19 revascularization and 12 apexification) with an average follow up time of 17 months and a recall rate of 63%. Tooth survival, success rate, and adverse events were analyzed. Changes in radiographic root length, width and area were quantified. Results The majority of treated teeth survived throughout the study period with 30/31 (97%) teeth surviving (18/19 (95%) revascularization, 12/12 apexification). Most cases were also clinically successful with 27/31 (87%) meeting criteria for success, (15/19 (78%) revascularization and 12/12 apexification; non-significant difference). A greater incidence of adverse events was observed in the revascularization group (8/19 (42%) versus 1/12 (11%) in apexification (Risk Ratio= 5.1, p=0.04, 95%CI (0.719, 35.48)). Although more revascularization cases than apexification cases demonstrated an increase in radiographic root area and width, the effect was not statistically significant. Conclusion In this study, revascularization was not superior to other apexification techniques in either clinical or radiographic outcomes. Studies with large subject cohorts, and long follow up periods are needed to evaluate outcomes of revascularization and apexification, while accounting for important co-variants relevant to clinical success. PMID:25069909

Advanced parental ages and low birth weight in autism spectrum disorders--rates and effect on functioning.

PubMed

Ben Itzchak, Esther; Lahat, Eli; Zachor, Ditza A

2011-01-01

(1) To assess the distribution of parental age and birth weight in a large cohort with autism spectrum disorder (ASD) and to compare them to Israeli national data. (2) To examine possible relationships between these risk factors and functioning. The study included 529 participants diagnosed with ASD using standardized tests: the Autism Diagnosis Interview-Revised and the Autism Diagnosis Observation Schedule (ADOS). Medical, developmental and familial histories (gender, age, pregnancy and birth information, parental ages) were obtained. Autism severity was assessed using the new ADOS severity scale and adaptive skill using the Vineland Adaptive Behavior Scales. Advanced parental age was associated with ASD. In the older age range the percentages of mothers (35-44 y) and fathers (30-40 y) were significantly higher in the ASD cohort in comparison to the Israeli newborn data. The ASD cohort had significantly higher percentages of low birth weight (<2500 g) and very low birth weight (VLBW<1500 g) in comparison to the Israeli newborn data. Of these risk factors, only VLBW was associated with lower adaptive functioning. The group with VLBW had lower scores in daily living, socialization and motor skills in comparison to the >1500 g group. Autism severity was not associated with advanced parental age or VLBW. The shift in parental age distribution and birth weight in our ASD cohort suggests that the increase in ASD prevalence in recent years might be associated with novel prenatal insults. An adverse fetal course resulting in VLBW may represent a "second hit" phenomenon, causing a poorer outcome. Copyright © 2011 Elsevier Ltd. All rights reserved.

Differential risks of cancer types in people with Parkinson's disease: a national record-linkage study.

PubMed

Ong, Eugene Liat Hui; Goldacre, Raph; Goldacre, Michael

2014-09-01

There is evidence that people with Parkinson's disease (PD) have a decreased risk of developing cancer. PD has also variably been shown to be associated with an increased risk of cancers like melanoma and breast. We investigated this relationship in a very large cohort of PD patients. We constructed two cohorts of people from an all-England record-linked hospital and mortality dataset spanning 1999-2011. One cohort comprised people with a record of PD; the other comprised people without a record of PD. We 'followed up' these two cohorts to determine observed and expected numbers of people with subsequent primary cancers in each, based on person-years at risk, and calculated standardised rate ratios (RRs). In 219,194 people with PD, the RR for all subsequent primary malignant cancers combined was 0.92 (95% confidence interval (CI) 0.91-0.93). Increased RRs (p<0.05) were found for six out of the 31 cancer types investigated, including breast, melanoma, uterus, kidney, and neurological malignancies. Decreased RRs were found for 11 cancer sites, including lung and colon cancer. We corroborate the findings of a reduced risk for the development of cancers in PD patients shown in smaller studies, including cancers associated and not known to be associated with smoking; and of an increased risk of melanoma and breast cancer. To the best of our knowledge, this is the first study to report an association between PD and elevated rates of uterine and renal cancer. Further work is warranted to understand the mechanisms behind these findings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Percutaneous Nephrolithotomy in the Superobese: A Comparison of Outcomes Based on Body Mass Index.

PubMed

Dauw, Casey A; Borofsky, Michael S; York, Nadya; Lingeman, James E

2016-09-01

Percutaneous nephrolithotomy (PCNL) is considered the gold standard for treatment of large renal calculi. Although several investigators have examined the feasibility and outcomes associated with PCNL in obese patients, these studies have been limited by small sample size, lack of a comparator group, or few patients at body mass index (BMI) extremes. We thus compared outcomes of superobese (BMI >50) patients undergoing PCNL vs both an "overweight" and "ideal" cohort. We used a prospectively maintained database to identify ideal (BMI 18.5-25), overweight (BMI 25.1-49.9), and superobese (BMI ≥50) patients who underwent PCNL. Our primary objective was to compare surgical outcomes between groups measured by the percent of patients who required secondary PCNL. We then compared complication rates, need for transfusion, and length of stay (LOS) using chi-square testing and ANOVA where appropriate. A total of 1152 patients were identified of which 254 were classified as ideal, 840 as overweight, and 58 as superobese. The overweight cohort had a higher mean age and greater proportion of males, whereas staghorn stones were more common in the superobese group. Comorbid conditions were more commonly observed in the superobese cohort. Otherwise, the groups were similar. Surgical outcomes were comparable with 47.2%, 42.0%, and 38.0% of ideal, overweight, and superobese patients requiring secondary PCNL (p = 0.25) with no difference in complication rates, need for transfusion, or LOS. PCNL can be effectively and safely performed in superobese patients with no difference in surgical outcomes or complications when compared to ideal or overweight patient cohorts.

Associations between fruit, vegetable and legume intakes and prostate cancer risk: results from the prospective Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort.

PubMed

Diallo, Abou; Deschasaux, Mélanie; Galan, Pilar; Hercberg, Serge; Zelek, Laurent; Latino-Martel, Paule; Touvier, Mathilde

2016-05-01

Although experimental studies suggest that fruits, vegetables and legumes may exert protective effects against prostate carcinogenesis through various bioactive compounds such as dietary fibre and antioxidants, epidemiological evidence is lacking. Notably, very few prospective studies have investigated the relationship between legume intake and prostate cancer risk. Our objective was to prospectively investigate the association between fruit, vegetable, tomato products, potatoes and legume intakes and prostate cancer risk. This study included 3313 male participants to the SUpplémentation en VItamines et Minéraux AntioXydants cohort (follow-up: 1994-2007) who completed at least three 24-h dietary records during the first 2 years of follow-up. Associations between tertiles of intake and prostate cancer risk were assessed by multivariate Cox proportional hazards models. After a median follow-up of 12·6 years, 139 incident prostate cancers were diagnosed. An inverse association was observed between prostate cancer risk and tertiles of legume intake (hazard ratio (HR)T3v.T1=0·53; 95 % CI 0·34, 0·85; P trend=0·009). This association was maintained after excluding soya and soya products from the legume group (HRT3 v.T1=0·56; 95 % CI 0·35, 0·89; P trend=0·02). No association was observed between prostate cancer risk and tertiles of intakes of fruits (P trend=0·25), vegetables (P trend=0·91), potatoes (P trend=0·77) and tomato products (P trend=0·09). This prospective study confirms the null association between fruit and non-starchy vegetable intakes and prostate cancer risk observed in most previous cohorts. In contrast, although very few prospective studies have been published on the topic, our results suggest an inverse association between legume intake and prostate cancer risk, supported by mechanistic plausibility. These results should be confirmed by large-scale observational and intervention studies.

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

Seasonal change in bone, muscle and fat in professional rugby league players and its relationship to injury: a cohort study

PubMed Central

Georgeson, Erin C; Weeks, Benjamin K; McLellan, Chris; Beck, Belinda R

2012-01-01

Objectives To examine the anthropometric characteristics of an Australian National Rugby League team and identify the relationship to type and incidence of injuries sustained during a professional season. It was hypothesised that body composition would not change discernibly across a season and that injury would be negatively related to preseason bone and muscle mass. Design A repeated measure, prospective, observational, cohort study. Setting Griffith University, Gold Coast, Australia. Participants 37 professional male Australian National Rugby League players, 24.3 (3.8) years of age were recruited for preseason 1 testing, of whom 25 were retested preseason 2. Primary and secondary outcome measures Primary outcome measures included biometrics; body composition (bone, muscle and fat mass; dual-energy x-ray absorptiometry; XR800, Norland Medical Systems, Inc); bone geometry and strength (peripheral quantitative CT; XCT 3000, Stratec); calcaneal broadband ultrasound attenuation (BUA; QUS-2, Quidel); diet and physical activity history. Secondary outcome measures included player injuries across a single playing season. Results Lean mass decreased progressively throughout the season (pre=81.45(7.76) kg; post=79.89(6.72) kg; p≤0.05), while whole body (WB) bone mineral density (BMD) increased until mid-season (pre=1.235(0.087) g/cm2; mid=1.296(0.093) g/cm2; p≤0.001) then decreased thereafter (post=1.256(0.100); p≤0.001). Start-of-season WB BMD, fat and lean mass, weight and tibial mass measured at the 38% site predicted bone injury incidence, but no other relationship was observed between body composition and injury. Conclusions Significant anthropometric changes were observed in players across a professional rugby league season, including an overall loss of muscle and an initial increase, followed by a decrease in bone mass. Strong relationships between anthropometry and incidence of injury were not observed. Long-term tracking of large rugby league cohorts is indicated to obtain more injury data in order to examine anthropometric relationships with greater statistical power. PMID:23135539

Reliability of plasma polar metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry.

PubMed

Harada, Sei; Hirayama, Akiyoshi; Chan, Queenie; Kurihara, Ayako; Fukai, Kota; Iida, Miho; Kato, Suzuka; Sugiyama, Daisuke; Kuwabara, Kazuyo; Takeuchi, Ayano; Akiyama, Miki; Okamura, Tomonori; Ebbels, Timothy M D; Elliott, Paul; Tomita, Masaru; Sato, Asako; Suzuki, Chizuru; Sugimoto, Masahiro; Soga, Tomoyoshi; Takebayashi, Toru

2018-01-01

Cohort studies with metabolomics data are becoming more widespread, however, large-scale studies involving 10,000s of participants are still limited, especially in Asian populations. Therefore, we started the Tsuruoka Metabolomics Cohort Study enrolling 11,002 community-dwelling adults in Japan, and using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography-mass spectrometry. The CE-MS method is highly amenable to absolute quantification of polar metabolites, however, its reliability for large-scale measurement is unclear. The aim of this study is to examine reproducibility and validity of large-scale CE-MS measurements. In addition, the study presents absolute concentrations of polar metabolites in human plasma, which can be used in future as reference ranges in a Japanese population. Metabolomic profiling of 8,413 fasting plasma samples were completed using CE-MS, and 94 polar metabolites were structurally identified and quantified. Quality control (QC) samples were injected every ten samples and assessed throughout the analysis. Inter- and intra-batch coefficients of variation of QC and participant samples, and technical intraclass correlation coefficients were estimated. Passing-Bablok regression of plasma concentrations by CE-MS on serum concentrations by standard clinical chemistry assays was conducted for creatinine and uric acid. In QC samples, coefficient of variation was less than 20% for 64 metabolites, and less than 30% for 80 metabolites out of the 94 metabolites. Inter-batch coefficient of variation was less than 20% for 81 metabolites. Estimated technical intraclass correlation coefficient was above 0.75 for 67 metabolites. The slope of Passing-Bablok regression was estimated as 0.97 (95% confidence interval: 0.95, 0.98) for creatinine and 0.95 (0.92, 0.96) for uric acid. Compared to published data from other large cohort measurement platforms, reproducibility of metabolites common to the platforms was similar to or better than in the other studies. These results show that our CE-MS platform is suitable for conducting large-scale epidemiological studies.

Prediction of Large Vessel Occlusions in Acute Stroke: National Institute of Health Stroke Scale Is Hard to Beat.

PubMed

Vanacker, Peter; Heldner, Mirjam R; Amiguet, Michael; Faouzi, Mohamed; Cras, Patrick; Ntaios, George; Arnold, Marcel; Mattle, Heinrich P; Gralla, Jan; Fischer, Urs; Michel, Patrik

2016-06-01

Endovascular treatment for acute ischemic stroke with a large vessel occlusion was recently shown to be effective. We aimed to develop a score capable of predicting large vessel occlusion eligible for endovascular treatment in the early hospital management. Retrospective, cohort study. Two tertiary, Swiss stroke centers. Consecutive acute ischemic stroke patients (1,645 patients; Acute STroke Registry and Analysis of Lausanne registry), who had CT angiography within 6 and 12 hours of symptom onset, were categorized according to the occlusion site. Demographic and clinical information was used in logistic regression analysis to derive predictors of large vessel occlusion (defined as intracranial carotid, basilar, and M1 segment of middle cerebral artery occlusions). Based on logistic regression coefficients, an integer score was created and validated internally and externally (848 patients; Bernese Stroke Registry). None. Large vessel occlusions were present in 316 patients (21%) in the derivation and 566 (28%) in the external validation cohort. Five predictors added significantly to the score: National Institute of Health Stroke Scale at admission, hemineglect, female sex, atrial fibrillation, and no history of stroke and prestroke handicap (modified Rankin Scale score, < 2). Diagnostic accuracy in internal and external validation cohorts was excellent (area under the receiver operating characteristic curve, 0.84 both). The score performed slightly better than National Institute of Health Stroke Scale alone regarding prediction error (Wilcoxon signed rank test, p < 0.001) and regarding discriminatory power in derivation and pooled cohorts (area under the receiver operating characteristic curve, 0.81 vs 0.80; DeLong test, p = 0.02). Our score accurately predicts the presence of emergent large vessel occlusions, which are eligible for endovascular treatment. However, incorporation of additional demographic and historical information available on hospital arrival provides minimal incremental predictive value compared with the National Institute of Health Stroke Scale alone.

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.

Lifestyle and Risk of Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Cohort of United States Male Health Professionals.

PubMed

Zhang, Ran; Sutcliffe, Siobhan; Giovannucci, Edward; Willett, Walter C; Platz, Elizabeth A; Rosner, Bernard A; Dimitrakoff, Jordan D; Wu, Kana

2015-11-01

Although chronic prostatitis/chronic pelvic pain syndrome is a prevalent urological disorder among men of all ages, its etiology remains unknown. Only a few previous studies have examined associations between lifestyle factors and chronic prostatitis/chronic pelvic pain syndrome, of which most were limited by the cross-sectional study design and lack of control for possible confounders. To address these limitations we performed a cohort study of major lifestyle factors (obesity, smoking and hypertension) and chronic prostatitis/chronic pelvic pain syndrome risk in the HPFS (Health Professionals Follow-up Study), a large ongoing cohort of United States based male health professionals. The HPFS includes 51,529 men who were 40 to 75 years old at baseline in 1986. At enrollment and every 2 years thereafter participants have completed questionnaires on lifestyle and health conditions. In 2008 participants completed an additional set of questions on recent chronic prostatitis/chronic pelvic pain syndrome pain symptoms modified from the NIH (National Institutes of Health)-CPSI (Chronic Prostatitis Symptom Index) as well as questions on approximate date of symptom onset. The 653 participants with NIH-CPSI pain scores 8 or greater who first experienced symptoms after 1986 were considered incident chronic prostatitis/chronic pelvic pain syndrome cases and the 19,138 who completed chronic prostatitis/chronic pelvic pain syndrome questions but did not report chronic prostatitis/chronic pelvic pain syndrome related pain were considered noncases. No associations were observed for baseline body mass index, waist circumference, waist-to-hip ratio, cigarette smoking and hypertension with chronic prostatitis/chronic pelvic pain syndrome risk (each OR ≤1.34). In this large cohort study none of the lifestyle factors examined was associated with chronic prostatitis/chronic pelvic pain syndrome risk. As the etiology of chronic prostatitis/chronic pelvic pain syndrome remains unknown, additional prospective studies are needed to elucidate modifiable risk factors for this common condition. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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

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.

Classical homeopathy in the treatment of cancer patients--a prospective observational study of two independent cohorts.

PubMed

Rostock, Matthias; Naumann, Johannes; Guethlin, Corina; Guenther, Lars; Bartsch, Hans H; Walach, Harald

2011-01-17

Many cancer patients seek homeopathy as a complementary therapy. It has rarely been studied systematically, whether homeopathic care is of benefit for cancer patients. We conducted a prospective observational study with cancer patients in two differently treated cohorts: one cohort with patients under complementary homeopathic treatment (HG; n = 259), and one cohort with conventionally treated cancer patients (CG; n = 380). For a direct comparison, matched pairs with patients of the same tumour entity and comparable prognosis were to be formed. Main outcome parameter: change of quality of life (FACT-G, FACIT-Sp) after 3 months. Secondary outcome parameters: change of quality of life (FACT-G, FACIT-Sp) after a year, as well as impairment by fatigue (MFI) and by anxiety and depression (HADS). HG: FACT-G, or FACIT-Sp, respectively improved statistically significantly in the first three months, from 75.6 (SD 14.6) to 81.1 (SD 16.9), or from 32.1 (SD 8.2) to 34.9 (SD 8.32), respectively. After 12 months, a further increase to 84.1 (SD 15.5) or 35.2 (SD 8.6) was found. Fatigue (MFI) decreased; anxiety and depression (HADS) did not change. CG: FACT-G remained constant in the first three months: 75.3 (SD 17.3) at t0, and 76.6 (SD 16.6) at t1. After 12 months, there was a slight increase to 78.9 (SD 18.1). FACIT-Sp scores improved significantly from t0 (31.0 - SD 8.9) to t1 (32.1 - SD 8.9) and declined again after a year (31.6 - SD 9.4). For fatigue, anxiety, and depression, no relevant changes were found. 120 patients of HG and 206 patients of CG met our criteria for matched-pairs selection. Due to large differences between the two patient populations, however, only 11 matched pairs could be formed. This is not sufficient for a comparative study. In our prospective study, we observed an improvement of quality of life as well as a tendency of fatigue symptoms to decrease in cancer patients under complementary homeopathic treatment. It would take considerably larger samples to find matched pairs suitable for comparison in order to establish a definite causal relation between these effects and homeopathic treatment.

Age, period and cohort effects on adult physical activity levels from 1991 to 2011 in China.

PubMed

Zang, Jiajie; Ng, Shu Wen

2016-04-20

To date no work has differentiated the effects of age, period, and cohort on physical activity (PA) among Chinese adults, while also considering biological, behavioral, economic, and environmental factors over time. We used data from the China Health and Nutrition Survey (CHNS) between 1991 and 2011 (20 years). The outcomes of interest are metabolic equivalent of task (MET) hours per week from work and domestic activities. Age, individual characteristics, household size, asset ownership, urbanization were included as covariates. Analyses for adult (≥20y) males (n = 29,343) and females (n = 31,094) was conducted to explicitly assess differences in PA due to age vs period effects, and implicitly assess differences by cohorts due to the period-specific experiences across individuals of varying ages. The mean age of the sample rose from 41.31 to 50.8 years and PA decreased from 427.75 ± 264.35 MET hours per week (MET-hr/wk) in 1991 to 245.99 ± 206.65 MET-hr/wk in 2011, with much steeper declines for women compared to men. For both genders, we found non-linear decreases in PA with age over time. Controlling for age effects, negative period effects on PA were observed in each survey year, and were substantial from 1993 to 2000 for males and from 1993 to 2011 for females. The interaction between survey year and age (P < 0.05) were observed from 2004 to 2011. Higher community urbanicity, vehicle ownership, TV and computer ownership, overweight and obese, higher education served as negative predictors. Bicycle ownership, bigger household size, non-professional jobs, being married and having more children (for women) were positive predictors of PA (P < 0.05). Furthermore, at any given age, individuals who were younger at baseline had higher mean PA compared with individuals older at baseline. This study followed a large cohort of adults over a significant portion of their lives. Strong age and secular trends were observed, resulting in an increasing number of participants who have or are likely to lower their PA levels. These trends suggest that tackling the rapid PA decline among its population is of high priority for China's public health outlook as its population ages and continues to experience significant economic and environmental changes.

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

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

Insecticide exposure and farm history in relation to risk of lymphomas and leukemias in the Women’s Health Initiative (WHI) observational study cohort

PubMed Central

Schinasi, L; De Roos, AJ; Ray, RM; Edlefsen, KL; Parks, CG; Howard, BV; Meliker; Bonner, MR; Wallace, RB; LaCroix, AZ

2017-01-01

Purpose Relationships of farm history and insecticide exposure at home or work with lymphohematopoietic (LH) neoplasm risk were investigated in a large prospective cohort of United States women. Methods In questionnaires, women self-reported history living or working on a farm, personally mixing or applying insecticides, insecticide application in the home or workplace by a commercial service, and treating pets with insecticides. Relationships with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, plasma cell neoplasms, and myeloid leukemia were investigated using Cox proportional hazard models. Age and farming history were explored as effect modifiers. Results The analysis included 76,493 women and 822 NHL cases. Women who ever lived or worked on a farm had 1.12 times the risk of NHL (95% CI: 0.95–1.32) compared to those who did not. Women who reported that a commercial service ever applied insecticides in their immediate surroundings had 65% higher risk of CLL/SLL (95% CI: 1.15–2.38). Women younger than 65 who ever applied insecticides had 87% higher risk of DLBCL (95% CI: 1.13–3.09). Conclusions Insecticide exposures may contribute to risk of CLL/SLL and DLBCL. Future studies should examine relationships of LH subtypes with specific types of household insecticides. PMID:26365305

Gastroduodenal Ulcers and ABO Blood Group: the Japan Nurses' Health Study (JNHS).

PubMed

Alkebsi, Lobna; Ideno, Yuki; Lee, Jung-Su; Suzuki, Shosuke; Nakajima-Shimada, Junko; Ohnishi, Hiroshi; Sato, Yasunori; Hayashi, Kunihiko

2018-01-05

Although several studies have shown that blood type O is associated with increased risk of peptic ulcer, few studies have investigated these associations in Japan. We sought to investigate the association between the ABO blood group and risk of gastroduodenal ulcers (GDU) using combined analysis of both retrospective and prospective data from a large cohort study of Japanese women, the Japan Nurses' Health Study (JNHS; n = 15,019). The impact of the ABO blood group on GDU risk was examined using Cox regression analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI), with adjustment for potential confounders. Compared with women with non-O blood types (A, B, and AB), women with blood type O had a significantly increased risk of GDU from birth (multivariable-adjusted HR 1.18; 95% CI, 1.04-1.34). Moreover, the highest cumulative incidence of GDU was observed in women born pre-1956 with blood type O. In a subgroup analysis stratified by birth year (pre-1956 or post-1955), the multivariable-adjusted HR of women with blood type O was 1.22 (95% CI, 1.00-1.49) and 1.15 (95% CI, 0.98-1.35) in the pre-1956 and post-1955 groups, respectively. In this large, combined, ambispective cohort study of Japanese women, older women with blood type O had a higher risk of developing GDU than those with other blood types.

Nearly Full Employment Recovery Among South African HIV Patients On Antiretroviral Therapy: Evidence From A Large Population Cohort

PubMed Central

Bor, Jacob; Tanser, Frank; Newell, Marie-Louise; Bärnighausen, Till

2013-01-01

Antiretroviral therapy for HIV may have important economic benefits for patients and their households. We quantified the impact of HIV treatment on employment status among HIV patients in rural South Africa who were enrolled in a public-sector HIV treatment program supported by the U.S. President’s Emergency Plan for AIDS Relief. We linked clinical data from more than 2000 patients in the treatment program with ten years of longitudinal socioeconomic data from a complete community-based population cohort of over 30,000 adults residing in the clinical catchment area. We estimated the employment effects of HIV treatment in fixed effects regressions. Four years after the initiation of antiretroviral therapy, employment among HIV patients had recovered to about 90 percent of baseline rates observed in the same patients three to five years before they started treatment. Many patients initiated treatment early enough that they were able to avoid any loss of employment due to HIV. These results represent the first estimates of employment recovery among HIV patients in a general population, relative to the employment levels that these patients had prior to job-threatening illness and the decision to seek care. We find large economic benefits to HIV treatment. For some patients, further gains could be obtained from initiating antiretroviral therapy earlier, prior to HIV-related job loss. PMID:22778335

Outcome-Dependent Sampling with Interval-Censored Failure Time Data

PubMed Central

Zhou, Qingning; Cai, Jianwen; Zhou, Haibo

2017-01-01

Summary Epidemiologic studies and disease prevention trials often seek to relate an exposure variable to a failure time that suffers from interval-censoring. When the failure rate is low and the time intervals are wide, a large cohort is often required so as to yield reliable precision on the exposure-failure-time relationship. However, large cohort studies with simple random sampling could be prohibitive for investigators with a limited budget, especially when the exposure variables are expensive to obtain. Alternative cost-effective sampling designs and inference procedures are therefore desirable. We propose an outcome-dependent sampling (ODS) design with interval-censored failure time data, where we enrich the observed sample by selectively including certain more informative failure subjects. We develop a novel sieve semiparametric maximum empirical likelihood approach for fitting the proportional hazards model to data from the proposed interval-censoring ODS design. This approach employs the empirical likelihood and sieve methods to deal with the infinite-dimensional nuisance parameters, which greatly reduces the dimensionality of the estimation problem and eases the computation difficulty. The consistency and asymptotic normality of the resulting regression parameter estimator are established. The results from our extensive simulation study show that the proposed design and method works well for practical situations and is more efficient than the alternative designs and competing approaches. An example from the Atherosclerosis Risk in Communities (ARIC) study is provided for illustration. PMID:28771664

Does acute maternal stress in pregnancy affect infant health outcomes? Examination of a large cohort of infants born after the terrorist attacks of September 11, 2001.

PubMed

Endara, Skye M; Ryan, Margaret A K; Sevick, Carter J; Conlin, Ava Marie S; Macera, Caroline A; Smith, Tyler C

2009-07-20

Infants in utero during the terrorist attacks of September 11, 2001 may have been negatively affected by maternal stress. Studies to date have produced contradictory results. Data for this retrospective cohort study were obtained from the Department of Defense Birth and Infant Health Registry and included up to 164,743 infants born to active-duty military families. Infants were considered exposed if they were in utero on September 11, 2001, while the referent group included infants gestating in the same period in the preceding and following year (2000 and 2002). We investigated the association of this acute stress during pregnancy with the infant health outcomes of male:female sex ratio, birth defects, preterm birth, and growth deficiencies in utero and in infancy. No difference in sex ratio was observed between infants in utero in the first trimester of pregnancy on September 11, 2001 and infants in the referent population. Examination of the relationship between first-trimester exposure and birth defects also revealed no significant associations. In adjusted multivariable models, neither preterm birth nor growth deficiencies were significantly associated with the maternal exposure to the stress of September 11 during pregnancy. The findings from this large population-based study suggest that women who were pregnant during the terrorist attacks of September 11, 2001 had no increased risk of adverse infant health outcomes.

Psychological job demands as a risk factor for common cold in a Dutch working population.

PubMed

Mohren, D C; Swaen, G M; Borm, P J; Bast, A; Galama, J M

2001-01-01

We investigated the effect of Psychological Job Demands (PJD) on the occurrence of the clinical symptoms of common cold. Subjects, participating in a large prospective cohort study on psychological determinants of fatigue at work, were asked to fill in a questionnaire on the occurrence of common cold during the previous four months. High PJD were considered as a potential risk factor. Other factors such as age, gender, and having young children were considered as potential confounders. In logistic regression analysis, the adjusted odds ratio (OR) for having a recent cold in subjects reporting high PJD vs. those reporting low PJD was 1.20 (95% confidence interval (CI), 1.08-1.33). A higher risk emerged among those with young children (OR, 1.70; 95% CI, 1.47-1.96), those having a history of asthma (OR, 1.69; 95% CI, 1.28-2.22), or being under the age of 40 (OR, 1.28; 95% CI, 1.14-1.43) and among smokers (OR, 1.23; 95% CI, 1.09-1.38). The results support an association between PJD and common cold. In spite of the almost inevitable shortcoming of a large cohort study using questionnaires, this study gave us the opportunity to study the relationship between common cold and work-related factors in a nonexperimental setting with participants observed in a natural environment with all the normal everyday hassles.

Intakes of caffeine, coffee and tea and risk of amyotrophic lateral sclerosis: Results from five cohort studies.

PubMed

Fondell, Elinor; O'Reilly, É Ilis J; Fitzgerald, Kathryn C; Falcone, Guido J; Kolonel, Laurence N; Park, Yikyung; Gapstur, Susan M; Ascherio, Alberto

2015-01-01

Caffeine is thought to be neuroprotective by antagonizing the adenosine A2A receptors in the brain and thereby protecting motor neurons from excitotoxicity. We examined the association between consumption of caffeine, coffee and tea and risk of amyotrophic lateral sclerosis (ALS). Longitudinal analyses based on over 1,010,000 males and females in five large cohort studies (the Nurses' Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health-AARP Diet and Health Study). Cohort-specific multivariable-adjusted risk ratios (RR) and 95% confidence intervals (CI) estimates of ALS incidence or death were estimated by Cox proportional hazards regression and pooled using random-effects models. Results showed that a total of 1279 cases of ALS were documented during a mean of 18 years of follow-up. Caffeine intake was not associated with ALS risk; the pooled multivariable-adjusted RR comparing the highest to the lowest quintile of intake was 0.96 (95% CI 0.81-1.16). Similarly, neither coffee nor tea was associated with ALS risk. In conclusion, the results of this large study do not support associations of caffeine or caffeinated beverages with ALS risk.

Intakes of caffeine, coffee and tea and risk of Amyotrophic Lateral Sclerosis: Results from five cohort studies

PubMed Central

Fondell, Elinor; O'Reilly, Éilis J.; Fitzgerald, Kathryn C.; Falcone, Guido J.; Kolonel, Laurence N.; Park, Yikyung; Gapstur, Susan M.; Ascherio, Alberto

2015-01-01

Objective Caffeine is thought to be neuroprotective by antagonizing the adenosine A2A receptors in the brain and thereby protecting motor neurons from excitotoxicity. We examined the association between consumption of caffeine, coffee and tea and risk of Amyotrophic Lateral Sclerosis (ALS). Methods Longitudinal analyses based on over 1 010 000 men and women in 5 large cohort studies [the Nurses’ Health Study, the Health Professionals Follow-up Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health – AARP Diet and Health Study]. Cohort-specific multivariable-adjusted risk ratios (RR) and 95% confidence intervals (CI) estimates of ALS incidence or death was estimated by Cox proportional hazards regression and pooled using random-effects models. Results A total of 1279 cases of ALS were documented during a mean of 18 years of follow-up. Caffeine intake was not associated with ALS risk; the pooled multivariable-adjusted RR comparing the highest to the lowest quintile of intake was 0.96 (95% CI 0.81-1.16). Similarly, neither coffee nor tea was associated with ALS risk. Conclusion The results of this large study do not support associations of caffeine or caffeinated beverages with ALS risk. PMID:25822002

Have children adapted to their mothers working, or was adaptation unnecessary? Cohort effects and the relationship between maternal employment and child well-being.

PubMed

Wills, Jeremiah B; Brauer, Jonathan R

2012-03-01

Drawing on previous theoretical and empirical work, we posit that maternal employment influences on child well-being vary across birth cohorts. We investigate this possibility by analyzing longitudinal data from a sample of children and their mothers drawn from the National Longitudinal Survey of Youth. We introduce a series of age, cohort, and maternal employment interaction terms into multilevel models predicting child well-being to assess whether any potential short-term or long-term effects of early and current maternal employment vary across birth cohorts. Results indicate that maternal employment largely is inconsequential to child well-being regardless of birth cohort, with a few exceptions. For instance, children born in earlier cohorts may have experienced long-term positive effects of having an employed mother; however, as maternal employment became more commonplace in recent cohorts, these beneficial effects appear to have disappeared. We discuss theoretical and methodological implications of these findings. Copyright © 2011 Elsevier Inc. All rights reserved.

Using Multiple Imputation to Assign Pesticide Use for Non-Responders in the Follow-Up Questionnaire in the Agricultural Health Study

EPA Science Inventory

The Agricultural Health Study (AHS), a large prospective cohort, was designed to elucidate associations between pesticide use and other agricultural exposures and health outcomes. The cohort includes 57,310 pesticide applicators who were enrolled between 1993 and 1997 in Iowa and...

Evaluating Long-Term Complex Professional Development: Using a Variation of the Cohort Control Design

ERIC Educational Resources Information Center

Sample Mcmeeking, Laura B.; Cobb, R. Brian; Basile, Carole

2010-01-01

This paper introduces a variation on the post-test only cohort control design and addresses questions concerning both the methodological credibility and the practical utility of employing this design variation in evaluations of large-scale complex professional development programmes in mathematics education. The original design and design…

Suicide Attempts and Severe Psychiatric Morbidity among Former Child Welfare Clients--A National Cohort Study

ERIC Educational Resources Information Center

Vinnerljung, Bo; Hjern, Anders; Lindblad, Frank

2006-01-01

Background: Few large sample studies have examined psychiatric morbidity among former child welfare/protection clients. In this study, risks for suicide attempts and severe psychiatric morbidity in younger years were assessed for former child welfare clients in ten national birth cohorts, comparing them with general population peers and…

Pre- and Postnatal Influences on Preschool Mental Health: A Large-Scale Cohort Study

ERIC Educational Resources Information Center

Robinson, Monique; Oddy, Wendy H.; Li, Jianghong; Kendall, Garth E.; de Klerk, Nicholas H.; Silburn, Sven R.; Zubrick, Stephen R.; Newnham, John P.; Stanley, Fiona J.; Mattes, Eugen

2008-01-01

Background: Methodological challenges such as confounding have made the study of the early determinants of mental health morbidity problematic. This study aims to address these challenges in investigating antenatal, perinatal and postnatal risk factors for the development of mental health problems in pre-school children in a cohort of Western…

Psychiatric Illness in a Cohort of Adults with Prader-Willi Syndrome

ERIC Educational Resources Information Center

Sinnema, Margje; Boer, Harm; Collin, Philippe; Maaskant, Marian A.; van Roozendaal, Kees E. P.; Schrander-Stumpel, Constance T. R. M.; Curfs, Leopold M. G.

2011-01-01

Previous studies have suggested an association between PWS and comorbid psychiatric illness. Data on prevalence rates of psychopathology is still scarce. This paper describes a large-scale, systematic study investigating the prevalence of psychiatric illness in a Dutch adult PWS cohort. One hundred and two individuals were screened for psychiatric…

Socioeconomic Status and Injury in a Cohort of Saskatchewan Farmers

ERIC Educational Resources Information Center

Pickett, William; Day, Andrew G.; Hagel, Louise; Sun, Xiaoqun; Day, Lesley; Marlenga, Barbara; Brison, Robert J.; Pahwa, Punam; Crowe, Trever; Voaklander, Donald C.; Dosman, James

2011-01-01

Purpose: To estimate the strength of relationships between socioeconomic status and injury in a large Canadian farm population. Methods: We conducted a prospective cohort study of 4,769 people from 2,043 farms in Saskatchewan, Canada. Participants reported socioeconomic exposures in 2007 and were followed for the occurrence of injury through 2009…

Child Maltreatment and Adolescent Mental Health Problems in a Large Birth Cohort

ERIC Educational Resources Information Center

Mills, Ryan; Scott, James; Alati, Rosa; O'Callaghan, Michael; Najman, Jake M.; Strathearn, Lane

2013-01-01

Objective: To examine whether notified child maltreatment is associated with adverse psychological outcomes in adolescence, and whether differing patterns of psychological outcome are seen depending on the type of maltreatment. Methods: The participants were 7,223 mother and child pairs enrolled in a population-based birth cohort study in…

[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

Analyses of Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics Pre and Post Short and Long-Duration Space Flights

NASA Technical Reports Server (NTRS)

Alperin, Noam; Barr, Yael; Lee, Sang H.; Mason,Sara; Bagci, Ahmet M.

2015-01-01

Preliminary results are based on analyses of data from 17 crewmembers. The initial analysis compares pre to post-flight changes in total cerebral blood flow (CBF) and craniospinal CSF flow volume. Total CBF is obtained by summation of the mean flow rates through the 4 blood vessels supplying the brain (right and left internal carotid and vertebral arteries). Volumetric flow rates were obtained using an automated lumen segmentation technique shown to have 3-4-fold improved reproducibility and accuracy over manual lumen segmentation (6). Two cohorts, 5 short-duration and 8 long-duration crewmembers, who were scanned within 3 to 8 days post landing were included (4 short-duration crewmembers with MRI scans occurring beyond 10 days post flight were excluded). The VIIP Clinical Practice Guideline (CPG) classification is being used initially as a measure for VIIP syndrome severity. Median CPG scores of the short and long-duration cohorts were similar, 2. Mean preflight total CBF for the short and long-duration cohorts were similar, 863+/-144 and 747+/-119 mL/min, respectively. Percentage CBF changes for all short duration crewmembers were 11% or lower, within the range of normal physiological fluctuations in healthy individuals. In contrast, in 4 of the 8 long-duration crewmembers, the change in CBF exceeded the range of normal physiological fluctuation. In 3 of the 4 subjects an increase in CBF was measured. Large pre to post-flight changes in the craniospinal CSF flow volume were found in 6 of the 8 long-duration crewmembers. Box-Whisker plots of the CPG and the percent CBF and CSF flow changes for the two cohorts are shown in Figure 4. Examples of CSF flow waveforms for a short and two long-duration (CPG 0 and 3) are shown in Figure 5. Changes in CBF and CSF flow dynamics larger than normal physiological fluctuations were observed in the long-duration crewmembers. Changes in CSF flow were more pronounced than changes in CBF. Decreased CSF flow dynamics were observed in a subject with VIIP signs. Study limitations include a slightly longer landing-to-MRI scan period for the short-duration cohort and limited sensitivity of the subjective discrete ordinal CPG scale. This limitation can be overcome by using imaging based parametric measures of VIIP severity such as globe deformation measures.

Linking Canadian Population Health Data: Maximizing the Potential of Cohort and Administrative Data

PubMed Central

Doiron, Dany; Raina, Parminder; Fortier, Isabel

2013-01-01

Linkage of data collected by large Canadian cohort studies with provincially managed administrative health databases can offer very interesting avenues for multidisciplinary and cost-effective health research in Canada. Successfully co-analyzing cohort data and administrative health data (AHD) can lead to research results capable of improving the health and well-being of Canadians and enhancing the delivery of health care services. However, such an endeavour will require strong coordination and long-term commitment between all stakeholders involved. The challenges and opportunities of a pan-Canadian cohort-to-AHD data linkage program have been considered by cohort study investigators and data custodians from each Canadian province. Stakeholders acknowledge the important public health benefits of establishing such a program and have established an action plan to move forward. PMID:23823892

Linking Canadian population health data: maximizing the potential of cohort and administrative data.

PubMed

Doiron, Dany; Raina, Parminder; Fortier, Isabel

2013-03-06

Linkage of data collected by large Canadian cohort studies with provincially managed administrative health databases can offer very interesting avenues for multidisciplinary and cost-effective health research in Canada. Successfully co-analyzing cohort data and administrative health data (AHD) can lead to research results capable of improving the health and well-being of Canadians and enhancing the delivery of health care services. However, such an endeavour will require strong coordination and long-term commitment between all stakeholders involved. The challenges and opportunities of a pan-Canadian cohort-to-AHD data linkage program have been considered by cohort study investigators and data custodians from each Canadian province. Stakeholders acknowledge the important public health benefits of establishing such a program and have established an action plan to move forward.

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…

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.

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.

Exploratory factor analysis of self-reported symptoms in a large, population-based military cohort

PubMed Central

2010-01-01

Background US military engagements have consistently raised concern over the array of health outcomes experienced by service members postdeployment. Exploratory factor analysis has been used in studies of 1991 Gulf War-related illnesses, and may increase understanding of symptoms and health outcomes associated with current military conflicts in Iraq and Afghanistan. The objective of this study was to use exploratory factor analysis to describe the correlations among numerous physical and psychological symptoms in terms of a smaller number of unobserved variables or factors. Methods The Millennium Cohort Study collects extensive self-reported health data from a large, population-based military cohort, providing a unique opportunity to investigate the interrelationships of numerous physical and psychological symptoms among US military personnel. This study used data from the Millennium Cohort Study, a large, population-based military cohort. Exploratory factor analysis was used to examine the covariance structure of symptoms reported by approximately 50,000 cohort members during 2004-2006. Analyses incorporated 89 symptoms, including responses to several validated instruments embedded in the questionnaire. Techniques accommodated the categorical and sometimes incomplete nature of the survey data. Results A 14-factor model accounted for 60 percent of the total variance in symptoms data and included factors related to several physical, psychological, and behavioral constructs. A notable finding was that many factors appeared to load in accordance with symptom co-location within the survey instrument, highlighting the difficulty in disassociating the effects of question content, location, and response format on factor structure. Conclusions This study demonstrates the potential strengths and weaknesses of exploratory factor analysis to heighten understanding of the complex associations among symptoms. Further research is needed to investigate the relationship between factor analytic results and survey structure, as well as to assess the relationship between factor scores and key exposure variables. PMID:20950474

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.

Maternal Continuing Folic Acid Supplementation after the First Trimester of Pregnancy Increased the Risk of Large-for-Gestational-Age Birth: A Population-Based Birth Cohort Study

PubMed Central

Wang, Sufang; Ge, Xing; Zhu, Beibei; Xuan, Yujie; Huang, Kun; Rutayisire, Erigene; Mao, Leijing; Huang, Sanhuan; Yan, Shuangqin; Tao, Fangbiao

2016-01-01

Supplementation with folic acid (FA) was proven to prevent neural tube defects (NTDs) and was recommended worldwide before and during early pregnancy. However, much less is known regarding the role of FA after the 12th gestational week (GW). This study aimed to investigate the related effects of continued FA supplementation after the first trimester of pregnancy on fetal growth. The study subjects came from the Ma’anshan-Anhui Birth Cohort Study (MABC) that recruited 3474 pregnant women from the city of Ma’anshan in Anhui Province in China during the period of May 2013 to September 2014. The information on use of vitamin and mineral supplements was recorded in different periods (the first/second/third trimester of pregnancy). Small-for-gestational-age (SGA) births were live-born infants that were <10th percentile of birth weight, and large-for-gestational-age (LGA) births were live-born infants that were ≥90th percentile of birth weight according to nomograms based on gender and gestational age from the latest standards. We used multivariable logistic regression to evaluate the effects of FA supplement consumption in the second/third trimester of pregnancy on the risk of LGA and SGA. In addition, propensity score analysis was also performed to examine the effects. In this prospective birth cohort study conducted in Chinese women who had taken FA in the first trimester of pregnancy, we found that continued FA supplementation with 400 micrograms/day in the second and third trimesters of pregnancy significantly increased the risk of LGA (RR = 1.98 (1.29, 3.04)). This relation was strong or monotonic after adjusting for maternal age, newborn’s gender, maternal pre-pregnancy BMI, maternal education level, smoking, alcohol consumption and calcium supplementation. We did not observe that continuing FA supplementation after the first trimester of pregnancy remarkably decreased the risk of SGA. The propensity score analysis showed similar results. To confirm these findings, additional investigations or trials with a large sample and the tracking of folate status throughout pregnancy are recommended. PMID:27537908

Survival in Women Versus Men Following Implantation of Pacemakers, Defibrillators, and Cardiac Resynchronization Therapy Devices in a Large, Nationwide Cohort.

PubMed

Varma, Niraj; Mittal, Suneet; Prillinger, Julie B; Snell, Jeff; Dalal, Nirav; Piccini, Jonathan P

2017-05-10

Whether outcomes differ between sexes following treatment with pacemakers (PM), implantable cardioverter defibrillators, and cardiac resynchronization therapy (CRT) devices is unclear. Consecutive US patients with newly implanted PM, implantable cardioverter defibrillators, and CRT devices from a large remote monitoring database between 2008 and 2011 were included in this observational cohort study. Sex-specific all-cause survival postimplant was compared within each device type using a multivariable Cox proportional hazards model, stratified on age and adjusted for remote monitoring utilization and ZIP-based socioeconomic variables. A total of 269 471 patients were assessed over a median 2.9 [interquartile range, 2.2, 3.6] years. Unadjusted mortality rates (MR; deaths/100 000 patient-years) were similar between women versus men receiving PMs (n=115 076, 55% male; MR 4193 versus MR 4256, respectively; adjusted hazard ratio, 0.87; 95% CI, 0.84-0.90; P <0.001) and implantable cardioverter defibrillators (n=85 014, 74% male; MR 4417 versus MR 4479, respectively; adjusted hazard ratio, 0.98; 95% CI, 0.93-1.02; P =0.244). In contrast, survival was superior in women receiving CRT defibrillators (n=61 475, 72% male; MR 5270 versus male MR 7175; adjusted hazard ratio, 0.73; 95% CI, 0.70-0.76; P <0.001) and also CRT pacemakers (n=7906, 57% male; MR 5383 versus male MR 7625, adjusted hazard ratio, 0.69; 95% CI, 0.61-0.78; P <0.001). This relative difference increased with time. These results were unaffected by age or remote monitoring utilization. Women accounted for less than 30% of high-voltage implants and fewer than half of low-voltage implants in a large, nation-wide cohort. Survival for women and men receiving implantable cardioverter defibrillators and PMs was similar, but dramatically greater for women receiving both defibrillator- and PM-based CRT. © 2017 The Authors and St. Jude Medical. Published on behalf of the American Heart Association, Inc., by Wiley.

Mortality among workers monitored for radiation exposure at the French nuclear fuel company.

PubMed

Metz-Flamant, C; Rogel, A; Caër, S; Samson, E; Laurier, D; Acker, A; Tirmarche, M

2009-01-01

A cohort of 9,285 nuclear workers employed at the French company AREVA NC specializing in the nuclear fuel cycle was established. Vital status, causes of death, employment characteristics and annual exposure to ionizing radiation were reconstructed for each individual over the time period 1977-2004. Standardized mortality ratios (SMRs) were computed using national mortality rates as an external reference. Tests for trends in mortality with duration of employment and cumulative external dose were performed. The all-cause and all-cancer mortality was significantly lower than expected from the French population. No significant excess among cancer sites studied was observed. Significant positive trends with cumulative dose were observed for colon and liver cancer and for respiratory diseases. Isolated significant trends should be carefully interpreted and considered in line with the large number of trend tests performed.

HIV Incidence and Risk Factors in Chinese Young Men Who Have Sex with Men—A Prospective Cohort Study

PubMed Central

Zhang, Hongbo; Dou, Zhi; Mi, Guodong; Ruan, Yuhua; Shen, Limei; Min, Xiangdong; Lan, Guanghua; Li, Fan; Li, Tian; Ning, Zhen; Wu, Guohui; She, Min; Wu, Zunyou

2014-01-01

Objectives To assess HIV incidence and its associated risk factors among young men who have sex with men (YMSM) in urban areas, China. Design The study used a prospective cohort study design and standard diagnostic tests. Methods A twelve-month prospective cohort study was conducted among YMSM (18–25 years old) in 8 large cities in China. The participants were recruited via snowball sampling. A total of 1102 HIV-negative YMSM completed baseline assessment, 878 YMSM participants completed 6-month follow-up, and 902 completed 12-month follow-up. HIV was screened by an enzyme-linked immunosorbent assay and confirmed with Western Blot. Syphilis was screened via rapid plasma reagent and confirmed by treponema pallidum particle agglutination assay. Results 78 HIV seroconversions were identified within 1168.4 person-year observations yielding an incidence rate of 6.7 per 100 person-years. HIV seroconversion was associated with non-student status (RR = 2.61, 90% CI = 1.3–5.26), low HIV transmission knowledge (RR = 8.87, 90% CI = 2.16–36.43), and syphilis infection (RR = 5.04, 90% CI = 2.57–9.90). Conclusions Incidence of HIV among YMSM is high in urban areas of China. Interventions measures are required to contain the HIV epidemic within this population. PMID:24878586

Trends in lung cancer incidence in Sweden with special reference to period and birth cohorts.

PubMed

Myrdal, G; Lambe, M; Bergström, R; Ekbom, A; Wagenius, G; Ståhle, E

2001-08-01

Sweden has one of the largest population-based cancer registers in the world that provides an opportunity to examine the trend of lung cancer incidence during a 35-year period. The primary aim of the present study was to estimate the effects of birth cohort, year of diagnosis (period), and age on the time trends of lung cancer incidence rates, and to analyze the gender-specific incidence of different histopathological types of lung cancer. Among men the age-standardized incidence rate increased steadily up to 1982, when a peak of 49 cases per 100,000 person-years was reached. Among women the incidence rate was lower and showed a monotonic increase throughout the observation period. The fastest rate of increase was noted among the youngest women. In women, but not in men, there was a steady increase in risk with each successive birth cohort. For both sexes there were large changes in the histopathological distributions of cases. The most notable was a major increase in adenocarcinomas. The overall age-adjusted incidence rate of lung cancer in Sweden has stabilized in men during the past two decades while rates are still increasing in women. In view of the continued high prevalence of smoking among young women, a future definite increase in the overall number of lung cancer cases in women can be expected.

Lack of association between arterial stiffness and genetic variants by genome-wide association scan.

PubMed

Park, Sungha; Lee, Ji-Young; Kim, Byeong-Keuk; Lee, Sang-Hak; Chang, Hyuk-Jae; Choi, DongHoon; Jang, Yangsoo

2015-01-01

Arterial stiffness is an independent predictor of cardiovascular disease risk. However, whether genetic risk variants are associated with arterial stiffness measures, such as pulse-wave velocity (PWV), is largely unknown. Therefore, we performed a genome-wide association study (GWAS) to identify single-nucleotide polymorphisms (SNPs) associated with PWV in a Korea population. Study participants consisted of 402 patients in the Yonsei cardiovascular genome center cohort. Arterial stiffness was measured as brachial-ankle pulse-wave velocity (baPWV). Genotyping was performed in 402 subjects with the Axiom Genome-Wide ASI 1 Array Plate containing more than 600,000 SNP markers. The findings were tested for replication in independent subjects from a community-based cohort of 1206 individuals, using a Taqman assay to include two candidate SNPs. Associations with PWV were evaluated using an additive genetic model that included age, gender, systolic blood pressure and diastolic blood pressure as covariates. GWAS and replication analyses were conducted using the measured genotype method implemented in PLINK and SAS. We observed two candidate SNPs associated with baPWV in GWAS: rs7271920 (p = 7.15 × 10(-9)) and rs10125157 (p = 8.25 × 10(-7)). However, neither of these was significant in the replication cohort. In summary, we did not identify any common genetic variants associated with baPWV in cardiovascular patients.

Inference and quantification of peptidoforms in large sample cohorts by SWATH-MS

PubMed Central

Röst, Hannes L; Ludwig, Christina; Buil, Alfonso; Bensimon, Ariel; Soste, Martin; Spector, Tim D; Dermitzakis, Emmanouil T; Collins, Ben C; Malmström, Lars; Aebersold, Ruedi

2017-01-01

The consistent detection and quantification of protein post-translational modifications (PTMs) across sample cohorts is an essential prerequisite for the functional analysis of biological processes. Data-independent acquisition (DIA), a bottom-up mass spectrometry based proteomic strategy, exemplified by SWATH-MS, provides complete precursor and fragment ion information of a sample and thus, in principle, the information to identify peptidoforms, the modified variants of a peptide. However, due to the convoluted structure of DIA data sets the confident and systematic identification and quantification of peptidoforms has remained challenging. Here we present IPF (Inference of PeptidoForms), a fully automated algorithm that uses spectral libraries to query, validate and quantify peptidoforms in DIA data sets. The method was developed on data acquired by SWATH-MS and benchmarked using a synthetic phosphopeptide reference data set and phosphopeptide-enriched samples. The data indicate that IPF reduced false site-localization by more than 7-fold in comparison to previous approaches, while recovering 85.4% of the true signals. IPF was applied to detect and quantify peptidoforms carrying ten different types of PTMs in DIA data acquired from more than 200 samples of undepleted blood plasma of a human twin cohort. The data approportioned, for the first time, the contribution of heritable, environmental and longitudinal effects on the observed quantitative variability of specific modifications in blood plasma of a human population. PMID:28604659

External validation of preexisting first trimester preeclampsia prediction models.

PubMed

Allen, Rebecca E; Zamora, Javier; Arroyo-Manzano, David; Velauthar, Luxmilar; Allotey, John; Thangaratinam, Shakila; Aquilina, Joseph

2017-10-01

To validate the increasing number of prognostic models being developed for preeclampsia using our own prospective study. A systematic review of literature that assessed biomarkers, uterine artery Doppler and maternal characteristics in the first trimester for the prediction of preeclampsia was performed and models selected based on predefined criteria. Validation was performed by applying the regression coefficients that were published in the different derivation studies to our cohort. We assessed the models discrimination ability and calibration. Twenty models were identified for validation. The discrimination ability observed in derivation studies (Area Under the Curves) ranged from 0.70 to 0.96 when these models were validated against the validation cohort, these AUC varied importantly, ranging from 0.504 to 0.833. Comparing Area Under the Curves obtained in the derivation study to those in the validation cohort we found statistically significant differences in several studies. There currently isn't a definitive prediction model with adequate ability to discriminate for preeclampsia, which performs as well when applied to a different population and can differentiate well between the highest and lowest risk groups within the tested population. The pre-existing large number of models limits the value of further model development and future research should be focussed on further attempts to validate existing models and assessing whether implementation of these improves patient care. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

In utero exposure to radiation and haematological malignancies: pooled analysis of Southern Urals cohorts

PubMed Central

Schüz, Joachim; Deltour, Isabelle; Krestinina, Lyudmila Y; Tsareva, Yulia V; Tolstykh, Evgenia I; Sokolnikov, Mikhail E; Akleyev, Alexander V

2017-01-01

Background: It is scientifically uncertain whether in utero exposure to low-dose ionising radiation increases the lifetime risk of haematological malignancies. Methods: We pooled two cohorts from the Southern Urals comprising offspring of female workers of a large nuclear facility (the Mayak Production Association) and of women living in areas along the Techa River contaminated by nuclear accidents/waste from the same facility, with detailed dosimetry. Results: The combined cohort totalled 19 536 subjects with 700 504 person-years at risk over the period of incidence follow-up, and slightly more over the period of mortality follow-up, yielding 58 incident cases and 36 deaths up to age 61 years. Risk was increased in subjects who received in utero doses of ⩾80 mGy (excess relative risk (ERR): 1.27; 95% confidence interval (CI): −0.20 to 4.71), and the risk increased consistently per 100 mGy of continuous exposure in utero (ERR: 0.77; CI: 0.02 to 2.56). No association was apparent in mortality-based analyses. Results for leukaemia and lymphoma were similar. A very weak positive association was observed between incidence and postnatal exposure. Conclusions: In summary, the results suggest a positive association between in utero exposure to ionising radiation and risk of haematological malignancies, but the small number of outcomes and inconsistent incidence and mortality findings preclude firm conclusions. PMID:27855443

The "DGPPN-Cohort": A national collaboration initiative by the German Association for Psychiatry and Psychotherapy (DGPPN) for establishing a large-scale cohort of psychiatric patients.

PubMed

Anderson-Schmidt, Heike; Adler, Lothar; Aly, Chadiga; Anghelescu, Ion-George; Bauer, Michael; Baumgärtner, Jessica; Becker, Joachim; Bianco, Roswitha; Becker, Thomas; Bitter, Cosima; Bönsch, Dominikus; Buckow, Karoline; Budde, Monika; Bührig, Martin; Deckert, Jürgen; Demiroglu, Sara Y; Dietrich, Detlef; Dümpelmann, Michael; Engelhardt, Uta; Fallgatter, Andreas J; Feldhaus, Daniel; Figge, Christian; Folkerts, Here; Franz, Michael; Gade, Katrin; Gaebel, Wolfgang; Grabe, Hans-Jörgen; Gruber, Oliver; Gullatz, Verena; Gusky, Linda; Heilbronner, Urs; Helbing, Krister; Hegerl, Ulrich; Heinz, Andreas; Hensch, Tilman; Hiemke, Christoph; Jäger, Markus; Jahn-Brodmann, Anke; Juckel, Georg; Kandulski, Franz; Kaschka, Wolfgang P; Kircher, Tilo; Koller, Manfred; Konrad, Carsten; Kornhuber, Johannes; Krause, Marina; Krug, Axel; Lee, Mahsa; Leweke, Markus; Lieb, Klaus; Mammes, Mechthild; Meyer-Lindenberg, Andreas; Mühlbacher, Moritz; Müller, Matthias J; Nieratschker, Vanessa; Nierste, Barbara; Ohle, Jacqueline; Pfennig, Andrea; Pieper, Marlenna; Quade, Matthias; Reich-Erkelenz, Daniela; Reif, Andreas; Reitt, Markus; Reininghaus, Bernd; Reininghaus, Eva Z; Riemenschneider, Matthias; Rienhoff, Otto; Roser, Patrik; Rujescu, Dan; Schennach, Rebecca; Scherk, Harald; Schmauss, Max; Schneider, Frank; Schosser, Alexandra; Schott, Björn H; Schwab, Sybille G; Schwanke, Jens; Skrowny, Daniela; Spitzer, Carsten; Stierl, Sebastian; Stöckel, Judith; Stübner, Susanne; Thiel, Andreas; Volz, Hans-Peter; von Hagen, Martin; Walter, Henrik; Witt, Stephanie H; Wobrock, Thomas; Zielasek, Jürgen; Zimmermann, Jörg; Zitzelsberger, Antje; Maier, Wolfgang; Falkai, Peter G; Rietschel, Marcella; Schulze, Thomas G

2013-12-01

The German Association for Psychiatry and Psychotherapy (DGPPN) has committed itself to establish a prospective national cohort of patients with major psychiatric disorders, the so-called DGPPN-Cohort. This project will enable the scientific exploitation of high-quality data and biomaterial from psychiatric patients for research. It will be set up using harmonised data sets and procedures for sample generation and guided by transparent rules for data access and data sharing regarding the central research database. While the main focus lies on biological research, it will be open to all kinds of scientific investigations, including epidemiological, clinical or health-service research.

Education in Twins and Their Parents Across Birth Cohorts Over 100 years: An Individual-Level Pooled Analysis of 42-Twin Cohorts.

PubMed

Silventoinen, Karri; Jelenkovic, Aline; Latvala, Antti; Sund, Reijo; Yokoyama, Yoshie; Ullemar, Vilhelmina; Almqvist, Catarina; Derom, Catherine A; Vlietinck, Robert F; Loos, Ruth J F; Kandler, Christian; Honda, Chika; Inui, Fujio; Iwatani, Yoshinori; Watanabe, Mikio; Rebato, Esther; Stazi, Maria A; Fagnani, Corrado; Brescianini, Sonia; Hur, Yoon-Mi; Jeong, Hoe-Uk; Cutler, Tessa L; Hopper, John L; Busjahn, Andreas; Saudino, Kimberly J; Ji, Fuling; Ning, Feng; Pang, Zengchang; Rose, Richard J; Koskenvuo, Markku; Heikkilä, Kauko; Cozen, Wendy; Hwang, Amie E; Mack, Thomas M; Siribaddana, Sisira H; Hotopf, Matthew; Sumathipala, Athula; Rijsdijk, Fruhling; Sung, Joohon; Kim, Jina; Lee, Jooyeon; Lee, Sooji; Nelson, Tracy L; Whitfield, Keith E; Tan, Qihua; Zhang, Dongfeng; Llewellyn, Clare H; Fisher, Abigail; Burt, S Alexandra; Klump, Kelly L; Knafo-Noam, Ariel; Mankuta, David; Abramson, Lior; Medland, Sarah E; Martin, Nicholas G; Montgomery, Grant W; Magnusson, Patrik K E; Pedersen, Nancy L; Dahl Aslan, Anna K; Corley, Robin P; Huibregtse, Brooke M; Öncel, Sevgi Y; Aliev, Fazil; Krueger, Robert F; McGue, Matt; Pahlen, Shandell; Willemsen, Gonneke; Bartels, Meike; van Beijsterveldt, Catharina E M; Silberg, Judy L; Eaves, Lindon J; Maes, Hermine H; Harris, Jennifer R; Brandt, Ingunn; Nilsen, Thomas S; Rasmussen, Finn; Tynelius, Per; Baker, Laura A; Tuvblad, Catherine; Ordoñana, Juan R; Sánchez-Romera, Juan F; Colodro-Conde, Lucia; Gatz, Margaret; Butler, David A; Lichtenstein, Paul; Goldberg, Jack H; Harden, K Paige; Tucker-Drob, Elliot M; Duncan, Glen E; Buchwald, Dedra; Tarnoki, Adam D; Tarnoki, David L; Franz, Carol E; Kremen, William S; Lyons, Michael J; Maia, José A; Freitas, Duarte L; Turkheimer, Eric; Sørensen, Thorkild I A; Boomsma, Dorret I; Kaprio, Jaakko

2017-10-01

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990-1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.

Global teaching and training initiatives for emerging cohort studies

PubMed Central

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

2015-01-01

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

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

PubMed

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

2016-01-01

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

Autism Traits in Individuals with Agenesis of the Corpus Callosum

ERIC Educational Resources Information Center

Lau, Yolanda C.; Hinkley, Leighton B. N.; Bukshpun, Polina; Strominger, Zoe A.; Wakahiro, Mari L. J.; Baron-Cohen, Simon; Allison, Carrie; Auyeung, Bonnie; Jeremy, Rita J.; Nagarajan, Srikantan S.; Sherr, Elliott H.; Marco, Elysa J.

2013-01-01

Autism spectrum disorders (ASD) have numerous etiologies, including structural brain malformations such as agenesis of the corpus callosum (AgCC). We sought to directly measure the occurrence of autism traits in a cohort of individuals with AgCC and to investigate the neural underpinnings of this association. We screened a large AgCC cohort (n =…

Predictors of mortality for juvenile trees in a residential urban-to-rural cohort in Worcester, MA

Treesearch

Arthur Elmes; John Rogan; Lara A. Roman; Christopher A. Williams; Samuel J. Ratick; David J. Nowak; Deborah G. Martin

2018-01-01

This paper explores predictors of juvenile tree mortality in a newly planted cohort in Worcester, MA, following an episode of large-scale tree removal necessitated by an Asian Longhorned Beetle (Anoplophora glabripennis, ALB) eradication program. Trees are increasingly seen as important providers of ecosystem services for urban areas, including:...

Strategies for Sustaining Quality in PBL Facilitation for Large Student Cohorts

ERIC Educational Resources Information Center

Young, Louise; Papinczak, Tracey

2013-01-01

Problem-based learning (PBL) has been used to scaffold and support student learning in many Australian medical programs, with the role of the facilitator in the process considered crucial to the overall educational experience of students. With the increasing size of student cohorts and in an environment of financial constraint, it is important to…

Trends in Childspacing: June 1975. Current Population Reports: Population Characteristics.

ERIC Educational Resources Information Center

Moore, Maurice J.; And Others

This report, largely statistical tables, presents data from the June 1975 Current Population Survey, on the timing and spacing of childbearing and discusses how such data is related to annual measures of fertility. By categorizing women according to their year of birth (birth cohort) or period of first marriage (marriage cohort), in addition to…

A Comparison of the PRIME-MD PHQ-9 and PHQ-8 in a Large Military Prospective Study, the Millennium Cohort Study

DTIC Science & Technology

2013-03-14

2007. Smallpox vaccination: comparison of self-reported and electronic vaccine records in the Millennium Cohort Study. Human. Vaccine 3, 6. Oquendo...Kim, H.M., McCarthy, J.F., Austin, K.L., Hoggatt, K.J., Walters, H., Valenstein, M., 2007. Suicide mortality among individuals receiving treatment

The Physical and Mental Health of A Large Military Cohort: Baseline Functional Health Status of the Millennium Cohort

DTIC Science & Technology

2007-11-26

Cohort T. C. Smith M. Zamorski, B. Smith, J. R. Riddle, C. A LeardMann T. S Wells, C. C. Engel, C. W. Hoge J. Adkins, D. Blaze for the...AUTHOR( S ) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) Naval Health Research Center,P.O...Box 85122,San Diego,CA,92186-5122 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME( S ) AND ADDRESS(ES) 10. SPONSOR

ProteinSeq: High-Performance Proteomic Analyses by Proximity Ligation and Next Generation Sequencing

PubMed Central

Vänelid, Johan; Siegbahn, Agneta; Ericsson, Olle; Fredriksson, Simon; Bäcklin, Christofer; Gut, Marta; Heath, Simon; Gut, Ivo Glynne; Wallentin, Lars; Gustafsson, Mats G.; Kamali-Moghaddam, Masood; Landegren, Ulf

2011-01-01

Despite intense interest, methods that provide enhanced sensitivity and specificity in parallel measurements of candidate protein biomarkers in numerous samples have been lacking. We present herein a multiplex proximity ligation assay with readout via realtime PCR or DNA sequencing (ProteinSeq). We demonstrate improved sensitivity over conventional sandwich assays for simultaneous analysis of sets of 35 proteins in 5 µl of blood plasma. Importantly, we observe a minimal tendency to increased background with multiplexing, compared to a sandwich assay, suggesting that higher levels of multiplexing are possible. We used ProteinSeq to analyze proteins in plasma samples from cardiovascular disease (CVD) patient cohorts and matched controls. Three proteins, namely P-selectin, Cystatin-B and Kallikrein-6, were identified as putative diagnostic biomarkers for CVD. The latter two have not been previously reported in the literature and their potential roles must be validated in larger patient cohorts. We conclude that ProteinSeq is promising for screening large numbers of proteins and samples while the technology can provide a much-needed platform for validation of diagnostic markers in biobank samples and in clinical use. PMID:21980495

Children's Contrast Sensitivity Function in Relation to Organophosphate Insecticide Prenatal Exposure in the Mother-Child PELAGIE Cohort.

PubMed

Cartier, Chloé; Warembourg, Charline; Monfort, Christine; Rouget, Florence; Limon, Gwendolina; Durand, Gaël; Cordier, Sylvaine; Saint-Amour, Dave; Chevrier, Cécile

2018-05-24

Human exposure to organophosphate pesticides (OP) is widespread. Several studies suggest that OP prenatal exposure alters the development of cognitive and behavioural functions in children, but the effects of OP prenatal exposure on child sensory functions are largely unknown. The aim of the study was to evaluate the association between OP prenatal exposure and visual processing in school-aged children from the mother-child PELAGIE cohort (France). OP biomarkers of exposure were measured in maternal urine samples at the beginning of pregnancy. The Functional Acuity Contrast Test (FACT) was used to assess visual contrast sensitivity in 180 children at 6 years of age. Linear regression models were performed on all children, and separately for boys and girls, taking into account various potential confounders, including maternal education and breastfeeding. No associations were observed in the whole sample, while maternal OP urinary metabolite levels were associated with a decrease of FACT scores in boys. These findings indicate that OP prenatal exposure might impair visual processing later in life in boys only. Copyright © 2018. Published by Elsevier B.V.

Genetic characterization of Greek population isolates reveals strong genetic drift at missense and trait-associated variants

PubMed Central

Panoutsopoulou, Kalliope; Hatzikotoulas, Konstantinos; Xifara, Dionysia Kiara; Colonna, Vincenza; Farmaki, Aliki-Eleni; Ritchie, Graham R. S.; Southam, Lorraine; Gilly, Arthur; Tachmazidou, Ioanna; Fatumo, Segun; Matchan, Angela; Rayner, Nigel W.; Ntalla, Ioanna; Mezzavilla, Massimo; Chen, Yuan; Kiagiadaki, Chrysoula; Zengini, Eleni; Mamakou, Vasiliki; Athanasiadis, Antonis; Giannakopoulou, Margarita; Kariakli, Vassiliki-Eirini; Nsubuga, Rebecca N.; Karabarinde, Alex; Sandhu, Manjinder; McVean, Gil; Tyler-Smith, Chris; Tsafantakis, Emmanouil; Karaleftheri, Maria; Xue, Yali; Dedoussis, George; Zeggini, Eleftheria

2014-01-01

Isolated populations are emerging as a powerful study design in the search for low-frequency and rare variant associations with complex phenotypes. Here we genotype 2,296 samples from two isolated Greek populations, the Pomak villages (HELIC-Pomak) in the North of Greece and the Mylopotamos villages (HELIC-MANOLIS) in Crete. We compare their genomic characteristics to the general Greek population and establish them as genetic isolates. In the MANOLIS cohort, we observe an enrichment of missense variants among the variants that have drifted up in frequency by more than fivefold. In the Pomak cohort, we find novel associations at variants on chr11p15.4 showing large allele frequency increases (from 0.2% in the general Greek population to 4.6% in the isolate) with haematological traits, for example, with mean corpuscular volume (rs7116019, P=2.3 × 10−26). We replicate this association in a second set of Pomak samples (combined P=2.0 × 10−36). We demonstrate significant power gains in detecting medical trait associations. PMID:25373335

Chloral hydrate sedation for magnetic resonance imaging in newborn infants.

PubMed

Finnemore, Anna; Toulmin, Hilary; Merchant, Naz; Arichi, Tom; Tusor, Nora; Cox, David; Ederies, Ash; Nongena, Phumza; Ko, Christopher; Dias, Ryan; Edwards, Anthony D; Groves, Alan M

2014-02-01

The aim of this study was to look for clinically significant adverse effects of chloral hydrate used in a large cohort of infants sedated for magnetic resonance imaging. Case notes of infants who underwent magnetic resonance imaging (MRI) scanning from 2008 to 2010 were reviewed, with patient demographics, sedation dose, comorbidities, time to discharge, and side effects of sedation noted. Four hundred and eleven infants (median [range] postmenstrual age per weight at scan 42 [31(+4) -60] weeks per 3500 g [1060-9900 g]) were sedated with chloral hydrate (median [range] dose 50 [20-80] mg·kg(-1)). In three cases (0.7%), desaturations occurred which prompted termination of the scan. One infant (0.2%) was admitted for additional observation following sedation but had no prolonged effects. In 17 (3.1%) cases, infants had desaturations which were self-limiting or responded to additional inspired oxygen such that scanning was allowed to continue. When adhering to strict protocols, MRI scanning in newborn infants in this cohort was performed using chloral hydrate sedation with a relatively low risk of significant adverse effects. © 2013 John Wiley & Sons Ltd.

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.

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.

All-Cause Mortality Trends in a Large Population-Based Cohort With Long-Standing Childhood-Onset Type 1 Diabetes

PubMed Central

Secrest, Aaron M.; Becker, Dorothy J.; Kelsey, Sheryl F.; LaPorte, Ronald E.; Orchard, Trevor J.

2010-01-01

OBJECTIVE Although management of type 1 diabetes improved dramatically in the 1980s, the effect on mortality is not clear. RESEARCH DESIGN AND METHODS We report trends in 30-year mortality using the Allegheny County (Pennsylvania) childhood-onset (age <18 years) type 1 diabetes registry (n = 1,075) with diagnosis from 1965–1979, by dividing the cohort into three diagnosis year cohorts (1965–1969, 1970–1974, and 1975–1979). Local (Allegheny County) mortality data were used to calculate standardized mortality ratios (SMRs). RESULTS As of 1 January 2008, vital status was ascertained for 97.0% of participants (n = 1,043) when mean age ± SD and duration of diabetes were 42.8 ± 8.0 and 32.0 ± 7.6 years, respectively. The 279 deaths (26.0%) observed were 7 times higher than expected (SMR 6.9 [95% CI 6.1–7.7]). An improving trend in SMR was seen by diagnosis cohort at 30 years of diabetes duration (9.3 [7.2–11.3], 7.5 [5.8–9.2], and 5.6 [4.0–7.2] for 1965–1969, 1970–1974, and 1975–1979, respectively). Although no sex difference in survival was observed (P = 0.27), female diabetic patients were 13 times more likely to die than age-matched women in the general population (SMR 13.2 [10.7–15.7]), much higher than the SMR for men (5.0 [4.0–6.0]). Conversely, whereas 30-year survival was significantly lower in African Americans than in Caucasians (57.2 vs. 82.7%, respectively; P < 0.001), no differences in SMR were seen by race. CONCLUSIONS Although survival has clearly improved, those with diabetes diagnosed most recently (1975–1979) still had a mortality rate 5.6 times higher than that seen in the general population, revealing a continuing need for improvements in treatment and care, particularly for women and African Americans with type 1 diabetes. PMID:21115767

Outcomes of special histotypes of breast cancer after adjuvant endocrine therapy with letrozole or tamoxifen in the monotherapy cohort of the BIG 1-98 trial.

PubMed

Munzone, E; Giobbie-Hurder, A; Gusterson, B A; Mallon, E; Viale, G; Thürlimann, B; Ejlertsen, B; MacGrogan, G; Bibeau, F; Lelkaitis, G; Price, K N; Gelber, R D; Coates, A S; Goldhirsch, A; Colleoni, M

2015-12-01

We investigated the outcomes of postmenopausal women with hormone receptor-positive, early breast cancer with special histotypes (mucinous, tubular, or cribriform) enrolled in the monotherapy cohort of the BIG 1-98 trial. The intention-to-treat BIG 1-98 monotherapy cohort (5 years of therapy with tamoxifen or letrozole) included 4922 women, of whom 4091 had central pathology review. Histotype groups were defined as: mucinous (N = 100), tubular/cribriform (N = 83), ductal (N = 3257), and other (N = 651). Of 183 women with either mucinous or tubular/cribriform tumors, 96 were randomly assigned to letrozole and 87 to tamoxifen. Outcomes assessed were disease-free survival (DFS), overall survival (OS), breast cancer-free interval (BCFI), and distant recurrence-free interval (DRFI). Median follow-up in the analytic cohort was 8.1 years. Women with tubular/cribriform breast cancer had the best outcomes for all end points compared with the other three histotypes, and had less breast cancer recurrence (97.5% 5-year BCFI) than those with mucinous (93.5%), ductal (88.9%), or other (89.9%) histotypes. Patients with mucinous or tubular/cribriform carcinoma had better DRFI (5-year rates 97.8% and 98.8%, respectively) than those with ductal (90.9%) or other (92.1%) carcinomas. Within the subgroup of women with special histotypes, we observed a nonsignificant increase in the hazard of breast cancer recurrence with letrozole [hazard (letrozole versus tamoxifen): 3.31, 95% confidence interval 0.94-11.7; P = 0.06]. Women with mucinous or tubular/cribriform breast cancer have better outcomes than those with other histotypes, although the observation is based on a limited number of events. In postmenopausal women with these histotypes, the magnitude of the letrozole advantage compared with tamoxifen may not be as large in patients with mucinous or tubular/cribriform disease. NCT00004205. © 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.

Rationale and design of three observational, prospective cohort studies including biobanking to evaluate and improve diagnostics, management strategies and risk stratification in venous thromboembolism: the VTEval Project.

PubMed

Frank, Bernd; Ariza, Liana; Lamparter, Heidrun; Grossmann, Vera; Prochaska, Jürgen H; Ullmann, Alexander; Kindler, Florentina; Weisser, Gerhard; Walter, Ulrich; Lackner, Karl J; Espinola-Klein, Christine; Münzel, Thomas; Konstantinides, Stavros V; Wild, Philipp S

2015-07-01

Venous thromboembolism (VTE) with its two manifestations deep vein thrombosis (DVT) and pulmonary embolism (PE) is a major public health problem. The VTEval Project aims to investigate numerous research questions on diagnosis, clinical management, treatment and prognosis of VTE, which have remained uncertain to date. The VTEval Project consists of three observational, prospective cohort studies on VTE comprising cohorts of individuals with a clinical suspicion of acute PE (with or without DVT), with a clinical suspicion of acute DVT (without symptomatic PE) and with an incidental diagnosis of VTE (PE or DVT). The VTEval Project expects to enrol a total of approximately 2000 individuals with subsequent active and passive follow-up investigations over a time period of 5 years per participant. Time points for active follow-up investigations are at months 3, 6, 12, 24 and 36 after diagnosis (depending on the disease cohort); passive follow-up investigations via registry offices and the cancer registry are performed 48 and 60 months after diagnosis for all participants. Primary short-term outcome is defined by overall mortality (PE-related death and all other causes of death), primary long-term outcome by symptomatic VTE (PE-related death, recurrence of non-fatal PE or DVT). The VTEval Project includes three 'all-comer' studies and involves the standardised acquisition of high-quality data, covering the systematic assessment of VTE including symptoms, risk profile, psychosocial, environmental and lifestyle factors as well as clinical and subclinical disease, and it builds up a large state-of-the-art biorepository containing various materials from serial blood samplings. The VTEval Project has been approved by the local data safety commissioner and the responsible ethics committee (reference no. 837.320.12 (8421-F)). Trial results will be published in peer-reviewed journals and presented at national and international scientific meetings. NCT02156401. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Setting up a cohort study in speech and language therapy: lessons from The UK Cleft Collective Speech and Language (CC-SL) study.

PubMed

Wren, Yvonne; Humphries, Kerry; Stock, Nicola Marie; Rumsey, Nichola; Lewis, Sarah; Davies, Amy; Bennett, Rhiannon; Sandy, Jonathan

2018-05-01

Efforts to increase the evidence base in speech and language therapy are often limited by methodological factors that have restricted the strength of the evidence to the lower levels of the evidence hierarchy. Where higher graded studies, such as randomized controlled trials, have been carried out, it has sometimes been difficult to obtain sufficient power to detect a potential effect of intervention owing to small sample sizes or heterogeneity in the participants. With certain clinical groups such as cleft lip and palate, systematic reviews of intervention studies have shown that there is no robust evidence to support the efficacy of any one intervention protocol over another. To describe the setting up of an observational clinical cohort study and to present this as an alternative design for answering research questions relating to prevalence, risk factors and outcomes from intervention. The Cleft Collective Speech and Language (CC-SL) study is a national cohort study of children born with cleft palate. Working in partnership with regional clinical cleft centres, a sample size of over 600 children and 600 parents is being recruited and followed up from birth to age 5 years. Variables being collected include demographic, psychological, surgical, hearing, and speech and language data. The process of setting up the study has led to the creation of a unique, large-scale data set which is available for researchers to access now and in future. As well as exploring predictive factors, the data can be used to explore the impact of interventions in relation to individual differences. Findings from these investigations can be used to provide information on sample criteria and definitions of intervention and dosage which can be used in future trials. The observational cohort study is a useful alternative design to explore questions around prevalence, risk factors and intervention for clinical groups where robust research data are not yet available. Findings from such a study can be used to guide service-delivery decisions and to determine power for future clinical trials. © 2017 Royal College of Speech and Language Therapists.

Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study.

PubMed

Palanca-Wessels, Maria Corinna A; Czuczman, Myron; Salles, Gilles; Assouline, Sarit; Sehn, Laurie H; Flinn, Ian; Patel, Manish R; Sangha, Randeep; Hagenbeek, Anton; Advani, Ranjana; Tilly, Herve; Casasnovas, Olivier; Press, Oliver W; Yalamanchili, Sreeni; Kahn, Robert; Dere, Randall C; Lu, Dan; Jones, Surai; Jones, Cheryl; Chu, Yu-Waye; Morschhauser, Franck

2015-06-01

Patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL) have an unfavourable prognosis with few treatment options. Polatuzumab vedotin is an antibody-drug conjugate containing an anti-CD79B monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the safety and clinical activity of polatuzumab vedotin in relapsed or refractory B-cell NHL and chronic lymphocytic leukaemia (CLL). In this phase 1, multicentre, open-label study, we enrolled patients with documented NHL or CLL expected to express CD79B (confirmation of CD79B expression was not required) and for whom no suitable therapy of curative intent or higher priority existed from 13 centres. The primary endpoints of the study were to assess safety and tolerability, determine the maximum tolerated dose, and identify the recommended phase 2 dose of polatuzumab vedotin as a single agent and in combination with rituximab. A 3 + 3 dose-escalation design was used in which we treated patients with polatuzumab vedotin (0·1-2·4 mg/kg every 21 days) in separate dose-escalation cohorts for NHL and CLL. After determination of the recommended phase 2 dose, we enrolled patients with relapsed or refractory diffuse large B-cell lymphoma and relapsed or refractory indolent NHL into indication-specific cohorts. We also enrolled patients with relapsed or refractory NHL into an additional cohort to assess the feasibility of the combination of polatuzumab vedotin and rituximab 375 mg/m(2). Patients who received any dose of polatuzumab vedotin were available for safety analyses. This study is registered with ClinicalTrials.gov, number NCT01290549. Between March 21, 2011, and Nov 30, 2012, we enrolled 95 patients (34 to the NHL dose-escalation cohort, 18 to the CLL dose-escalation cohort, 34 with NHL to the expansion cohort at the recommended phase 2 dose, and nine with NHL to the rituximab combination cohort; no expansion cohort of CLL was started due to lack of activity in the dose-escalation cohort). The recommended phase 2 dose in NHL was 2·4 mg/kg as a single agent and in combination with rituximab; the maximum tolerated dose in CLL was 1·0 mg/kg as a result of dose-limiting toxic effects reported in two of five patients given 1·8 mg/kg. Grade 3-4 adverse events were reported in 26 (58%) of 45 patients with NHL treated at the single-agent recommended phase 2 dose, and the most common grade 3-4 adverse events were neutropenia (18 [40%] of 45), anaemia (five [11%]), and peripheral sensory neuropathy (four [9%]). Serious adverse events were reported in 17 (38%) of 45 patients, and included diarrhoea (two patients), lung infection (two patients), disease progression (two patients), and lung disorder (two patients). Seven (77%) of nine patients in the rituximab combination cohort had a grade 3-4 adverse event, with neutropenia (five [56%]), anaemia (two [22%]), and febrile neutropenia (two [22%]) reported in more than one patient. 11 (12%) of 95 patients died during the study: eight with relapsed or refractory diffuse large B-cell lymphoma (due to progressive disease in four patients, infections in three patients [two treatment related], and treatment-related worsening ascites in one patient) and three with relapsed or refractory CLL (due to progressive disease, pulmonary infection, and pneumonia; none thought to be treatment-related). At the recommended phase 2 dose, objective responses were noted in 23 of 42 activity-evaluable patients with NHL given single-agent polatuzumab vedotin (14 of 25 with diffuse large B-cell lymphoma, seven of 15 with indolent NHL, and two with mantle-cell lymphoma) and seven of nine patients treated with polatuzumab vedotin combined with rituximab. No objective responses were observed in patients with CLL. Polatuzumab vedotin has an acceptable safety and tolerability profile in patients with NHL but not in those with CLL. Its clinical activity should be further assessed in NHL. Genentech. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

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.

Contrasting clinical outcomes in two cohorts of cats naturally infected with feline immunodeficiency virus (FIV).

PubMed

Bęczkowski, Paweł M; Litster, Annette; Lin, Tsang Long; Mellor, Dominic J; Willett, Brian J; Hosie, Margaret J

2015-03-23

Despite over 25 years of feline immunodeficiency virus (FIV) research, relatively little is known about the longitudinal course of FIV infection following natural infection. In contrast to published reports of experimental infections using lethal strains of the virus, clinical signs of naturally acquired FIV infection can be mild or inapparent, rather than life-threatening. In this prospective, longitudinal controlled study, based in Chicago, IL (n=17) and Memphis, TN (n=27), we investigated two cohorts of privately owned, naturally infected cats kept under different housing conditions. Cats in the Chicago cohort (Group 1) were kept in households of ≤2 cats, while the Memphis cohort (Group 2) comprised part of a large multi-cat household of over 60 cats kept indoors only, with unrestricted access to one another. The majority of cats from Group 1 did not display clinical signs consistent with immunodeficiency during the 22-month observation period. In contrast, the outcome of infection in Group 2 was dramatically different; 17/27 (63%) of cats lost a median of 51.3% of their bodyweight (P<0.0005) and died during the study period, with lymphoma being the most common cause of mortality. Although the decrease in CD4+ T cell count between enrolment and terminal disease was significant (P=0.0017), the CD4:CD8 ratio at the time of enrolment did not reliably distinguish FIV-positive cats classified as 'healthy' and 'not healthy' at either cohort. FIV load at enrolment was significantly lower in Group 1 than in Group 2 (P<0.0001), but there were no significant differences at enrolment between healthy and not healthy cats at either group. In conclusion, the results of this study suggest that management and housing conditions impact on disease progression and survival times of FIV-positive cats. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Mortality Attributable to Low Levels of Education in the United States.

PubMed

Krueger, Patrick M; Tran, Melanie K; Hummer, Robert A; Chang, Virginia W

2015-01-01

Educational disparities in U.S. adult mortality are large and have widened across birth cohorts. We consider three policy relevant scenarios and estimate the mortality attributable to: (1) individuals having less than a high school degree rather than a high school degree, (2) individuals having some college rather than a baccalaureate degree, and (3) individuals having anything less than a baccalaureate degree rather than a baccalaureate degree, using educational disparities specific to the 1925, 1935, and 1945 cohorts. We use the National Health Interview Survey data (1986-2004) linked to prospective mortality through 2006 (N=1,008,949), and discrete-time survival models, to estimate education- and cohort-specific mortality rates. We use those mortality rates and data on the 2010 U.S. population from the American Community Survey, to calculate annual attributable mortality estimates. If adults aged 25-85 in the 2010 U.S. population experienced the educational disparities in mortality observed in the 1945 cohort, 145,243 deaths could be attributed to individuals having less than a high school degree rather than a high school degree, 110,068 deaths could be attributed to individuals having some college rather than a baccalaureate degree, and 554,525 deaths could be attributed to individuals having anything less than a baccalaureate degree rather than a baccalaureate degree. Widening educational disparities between the 1925 and 1945 cohorts result in a doubling of attributable mortality. Mortality attributable to having less than a high school degree is proportionally similar among women and men and among non-Hispanic blacks and whites, and is greater for cardiovascular disease than for cancer. Mortality attributable to low education is comparable in magnitude to mortality attributable to individuals being current rather than former smokers. Existing research suggests that a substantial part of the association between education and mortality is causal. Thus, policies that increase education could significantly reduce adult mortality.

Pharmacokinetic modeling of gentamicin in treatment of infective endocarditis: Model development and validation of existing models.

PubMed

Gomes, Anna; van der Wijk, Lars; Proost, Johannes H; Sinha, Bhanu; Touw, Daan J

2017-01-01

Gentamicin shows large variations in half-life and volume of distribution (Vd) within and between individuals. Thus, monitoring and accurately predicting serum levels are required to optimize effectiveness and minimize toxicity. Currently, two population pharmacokinetic models are applied for predicting gentamicin doses in adults. For endocarditis patients the optimal model is unknown. We aimed at: 1) creating an optimal model for endocarditis patients; and 2) assessing whether the endocarditis and existing models can accurately predict serum levels. We performed a retrospective observational two-cohort study: one cohort to parameterize the endocarditis model by iterative two-stage Bayesian analysis, and a second cohort to validate and compare all three models. The Akaike Information Criterion and the weighted sum of squares of the residuals divided by the degrees of freedom were used to select the endocarditis model. Median Prediction Error (MDPE) and Median Absolute Prediction Error (MDAPE) were used to test all models with the validation dataset. We built the endocarditis model based on data from the modeling cohort (65 patients) with a fixed 0.277 L/h/70kg metabolic clearance, 0.698 (±0.358) renal clearance as fraction of creatinine clearance, and Vd 0.312 (±0.076) L/kg corrected lean body mass. External validation with data from 14 validation cohort patients showed a similar predictive power of the endocarditis model (MDPE -1.77%, MDAPE 4.68%) as compared to the intensive-care (MDPE -1.33%, MDAPE 4.37%) and standard (MDPE -0.90%, MDAPE 4.82%) models. All models acceptably predicted pharmacokinetic parameters for gentamicin in endocarditis patients. However, these patients appear to have an increased Vd, similar to intensive care patients. Vd mainly determines the height of peak serum levels, which in turn correlate with bactericidal activity. In order to maintain simplicity, we advise to use the existing intensive-care model in clinical practice to avoid potential underdosing of gentamicin in endocarditis patients.

Pharmacokinetic modeling of gentamicin in treatment of infective endocarditis: Model development and validation of existing models

PubMed Central

van der Wijk, Lars; Proost, Johannes H.; Sinha, Bhanu; Touw, Daan J.

2017-01-01

Gentamicin shows large variations in half-life and volume of distribution (Vd) within and between individuals. Thus, monitoring and accurately predicting serum levels are required to optimize effectiveness and minimize toxicity. Currently, two population pharmacokinetic models are applied for predicting gentamicin doses in adults. For endocarditis patients the optimal model is unknown. We aimed at: 1) creating an optimal model for endocarditis patients; and 2) assessing whether the endocarditis and existing models can accurately predict serum levels. We performed a retrospective observational two-cohort study: one cohort to parameterize the endocarditis model by iterative two-stage Bayesian analysis, and a second cohort to validate and compare all three models. The Akaike Information Criterion and the weighted sum of squares of the residuals divided by the degrees of freedom were used to select the endocarditis model. Median Prediction Error (MDPE) and Median Absolute Prediction Error (MDAPE) were used to test all models with the validation dataset. We built the endocarditis model based on data from the modeling cohort (65 patients) with a fixed 0.277 L/h/70kg metabolic clearance, 0.698 (±0.358) renal clearance as fraction of creatinine clearance, and Vd 0.312 (±0.076) L/kg corrected lean body mass. External validation with data from 14 validation cohort patients showed a similar predictive power of the endocarditis model (MDPE -1.77%, MDAPE 4.68%) as compared to the intensive-care (MDPE -1.33%, MDAPE 4.37%) and standard (MDPE -0.90%, MDAPE 4.82%) models. All models acceptably predicted pharmacokinetic parameters for gentamicin in endocarditis patients. However, these patients appear to have an increased Vd, similar to intensive care patients. Vd mainly determines the height of peak serum levels, which in turn correlate with bactericidal activity. In order to maintain simplicity, we advise to use the existing intensive-care model in clinical practice to avoid potential underdosing of gentamicin in endocarditis patients. PMID:28475651

Mortality Attributable to Low Levels of Education in the United States

PubMed Central

Krueger, Patrick M.; Tran, Melanie K.; Hummer, Robert A.; Chang, Virginia W.

2015-01-01

Background Educational disparities in U.S. adult mortality are large and have widened across birth cohorts. We consider three policy relevant scenarios and estimate the mortality attributable to: (1) individuals having less than a high school degree rather than a high school degree, (2) individuals having some college rather than a baccalaureate degree, and (3) individuals having anything less than a baccalaureate degree rather than a baccalaureate degree, using educational disparities specific to the 1925, 1935, and 1945 cohorts. Methods We use the National Health Interview Survey data (1986–2004) linked to prospective mortality through 2006 (N=1,008,949), and discrete-time survival models, to estimate education- and cohort-specific mortality rates. We use those mortality rates and data on the 2010 U.S. population from the American Community Survey, to calculate annual attributable mortality estimates. Results If adults aged 25–85 in the 2010 U.S. population experienced the educational disparities in mortality observed in the 1945 cohort, 145,243 deaths could be attributed to individuals having less than a high school degree rather than a high school degree, 110,068 deaths could be attributed to individuals having some college rather than a baccalaureate degree, and 554,525 deaths could be attributed to individuals having anything less than a baccalaureate degree rather than a baccalaureate degree. Widening educational disparities between the 1925 and 1945 cohorts result in a doubling of attributable mortality. Mortality attributable to having less than a high school degree is proportionally similar among women and men and among non-Hispanic blacks and whites, and is greater for cardiovascular disease than for cancer. Conclusions Mortality attributable to low education is comparable in magnitude to mortality attributable to individuals being current rather than former smokers. Existing research suggests that a substantial part of the association between education and mortality is causal. Thus, policies that increase education could significantly reduce adult mortality. PMID:26153885

Mitochondrial Haplogroup T Is Associated with Obesity in Austrian Juveniles and Adults

PubMed Central

Ebner, Sabine; Mangge, Harald; Langhof, Helmut; Halle, Martin; Siegrist, Monika; Aigner, Elmar; Paulmichl, Katharina; Paulweber, Bernhard; Datz, Christian; Sperl, Wolfgang; Kofler, Barbara; Weghuber, Daniel

2015-01-01

Background Recent publications have reported contradictory data regarding mitochondrial DNA (mtDNA) variation and its association with body mass index. The aim of the present study was to compare the frequencies of mtDNA haplogroups as well as control region (CR) polymorphisms of obese juveniles (n = 248) and obese adults (n = 1003) versus normal weight controls (njuvenile = 266, nadults = 595) in a well-defined, ethnically homogenous, age-matched comparative cohort of Austrian Caucasians. Methodology and Principal Findings Using SNP analysis and DNA sequencing, we identified the nine major European mitochondrial haplogroups and CR polymorphisms. Of these, only the T haplogroup frequency was increased in the juvenile obese cohort versus the control subjects [11.7% in obese vs. 6.4% in controls], although statistical significance was lost after adjustment for sex and age. Similar data were observed in a local adult cohort, in which haplogroup T was found at a significantly higher frequency in the overweight and obese subjects than in the normal weight group [9.7% vs. 6.2%, p = 0.012, adjusted for sex and age]. When all obese subjects were considered together, the difference in the frequency of haplogroup T was even more clearly seen [10.1% vs. 6.3%, p = 0.002, OR (95% CI) 1.71 (1.2–2.4), adjusted for sex and age]. The frequencies of the T haplogroup-linked CR polymorphisms C16294T and the C16296T were found to be elevated in both the juvenile and the adult obese cohort compared to the controls. Nevertheless, no mtDNA haplogroup or CR polymorphism was robustly associated with any of several investigated metabolic and cardiovascular parameters (e.g., blood pressure, blood glucose concentration, triglycerides, cholesterol) in all obese subjects. Conclusions and Significance By investigation of this large ethnically and geographically homogenous cohort of Middle European Caucasians, only mtDNA haplogroup T was identified as an obesity risk factor. PMID:26322975

Cardiovascular disease in Adult Life after Childhood Cancer in Scandinavia: A population-based cohort study of 32,308 one-year survivors.

PubMed

Gudmundsdottir, Thorgerdur; Winther, Jeanette F; de Fine Licht, Sofie; Bonnesen, Trine G; Asdahl, Peter H; Tryggvadottir, Laufey; Anderson, Harald; Wesenberg, Finn; Malila, Nea; Hasle, Henrik; Olsen, Jørgen H

2015-09-01

The lifetime risk for cardiovascular disease in a large cohort of childhood cancer survivors has not been fully assessed. In a retrospective population-based cohort study predicated on comprehensive national health registers, we identified a cohort of 32,308 one-year survivors of cancer diagnosed before the age of 20 in the five Nordic countries between the start of cancer registration in the 1940s and 1950s to 2008; 211,489 population comparison subjects were selected from national population registers. Study subjects were linked to national hospital registers, and the observed numbers of first hospital admission for cardiovascular disease among survivors were compared with the expected numbers derived from the population comparison cohort. Cardiovascular disease was diagnosed in 2,632 childhood cancer survivors (8.1%), yielding a standardized hospitalization rate ratio (RR) of 2.1 (95% CI 2.0-2.2) and an overall absolute excess risk (AER) of 324 per 100,000 person-years. At the end of follow-up 12% of the survivors were ≥ 50 years of age and 4.5% ≥ 60 years of age. Risk estimates were significantly increased throughout life, with an AER of ∼500-600 per 100,000 person-years at age ≥ 40. The highest relative risks were seen for heart failure (RR, 5.2; 95% CI 4.5-5.9), valvular dysfunction (4.6; 3.8-5.5) and cerebrovascular diseases (3.7; 3.4-4.1). Survivors of hepatic tumor, Hodgkin lymphoma and leukemia had the highest overall risks for cardiovascular disease, although each main type of childhood cancer had increased risk with different risk profiles. Nordic childhood cancer survivors are at markedly increased risk for cardiovascular disorders throughout life. These findings indicate the need for preventive interventions and continuous follow-up for this rapidly growing population. © 2015 UICC.

High red meat intake and all-cause cardiovascular and cancer mortality: is the risk modified by fruit and vegetable intake?

PubMed

Bellavia, Andrea; Stilling, Frej; Wolk, Alicja

2016-10-01

High red meat consumption is associated with a shorter survival and higher risk of cardiovascular disease (CVD), cancer, and all-cause mortality. Fruit and vegetable (FV) consumption is associated with a longer survival and lower mortality risk. Whether high FV consumption can counterbalance the negative impact of high red meat consumption is unknown. We evaluated 2 large prospective cohorts of Swedish men and women (the Swedish Mammography Cohort and the Cohort of Swedish Men) to determine whether the association between red meat consumption and the risk of all-cause, CVD, and cancer-specific mortality differs across amounts of FV intake. The study population included 74,645 Swedish men and women. Red meat and FV consumption were assessed through a self-administered questionnaire. We estimated HRs of all-cause, CVD, and cancer mortality according to quintiles of total red meat consumption. We next investigated possible interactions between red meat and FV consumption and evaluated the dose-response associations at low, medium, and high FV intake. Compared with participants in the lowest quintile of total red meat consumption, those in the highest quintile had a 21% increased risk of all-cause mortality (HR: 1.21; 95% CI: 1.13, 1.29), a 29% increased risk of CVD mortality (HR: 1.29; 95% CI: 1.14, 1.46), and no increase in the risk of cancer mortality (HR: 1.00; 95% CI: 0.88, 1.43). Results were remarkably similar across amounts of FV consumption, and no interaction between red meat and FV consumption was detected. High intakes of red meat were associated with a higher risk of all-cause and CVD mortality. The increased risks were consistently observed in participants with low, medium, and high FV consumption. The Swedish Mammography Cohort and the Cohort of Swedish Men were registered at clinicaltrials.gov as NCT01127698 and NCT01127711, respectively. © 2016 American Society for Nutrition.

Early Childhood Development and Schooling Attainment: Longitudinal Evidence from British, Finnish and Philippine Birth Cohorts.

PubMed

Peet, Evan D; McCoy, Dana C; Danaei, Goodarz; Ezzati, Majid; Fawzi, Wafaie; Jarvelin, Marjo-Riitta; Pillas, Demetris; Fink, Günther

2015-01-01

While recent literature has highlighted the importance of early childhood development for later life outcomes, comparatively little is known regarding the relative importance of early physical and cognitive development in predicting educational attainment cross-culturally. We used prospective data from three birth cohorts: the Northern Finland Birth Cohort of 1986 (NFBC1986), the 1970 British Cohort Study (BCS1970), and the Cebu Longitudinal Health and Nutrition Survey of 1983 (CLHNS) to assess the association of height-for-age z-score (HAZ) and cognitive development measured prior to age 8 with schooling attainment. Multivariate linear regression models were used to estimate baseline and adjusted associations. Both physical and cognitive development were highly predictive of adult educational attainment conditional on parental characteristics. The largest positive associations between physical development and schooling were found in the CLHNS (β = 0.53, 95%-CI: [0.32, 0.74]) with substantially smaller associations in the BCS1970 (β = 0.10, 95% CI [0.04, 0.16]) and the NFBC1986 (β = 0.06, 95% CI [-0.05, 0.16]). Strong associations between cognitive development and educational attainment were found for all three cohorts (NFBC1986: β = 0.22, 95%-CI: [0.12, 0.31], BCS1970: β = 0.58, 95%-CI: [0.52, 0.64], CLHNS: β = 1.08, 95%-CI: [0.88, 1.27]). Models jointly estimating educational associations of physical and cognitive development demonstrated weaker associations for physical development and minimal changes for cognitive development. The results indicate that although physical and cognitive early development are both important predictors of educational attainment, cognitive development appears to play a particularly important role. The large degree of heterogeneity in the observed effect sizes suggest that the importance of early life physical growth and cognitive development is highly dependent on socioeconomic and institutional contexts.

Rapid Rule-Out of Acute Myocardial Injury Using a Single High-Sensitivity Cardiac Troponin I Measurement.

PubMed

Sandoval, Yader; Smith, Stephen W; Shah, Anoop S V; Anand, Atul; Chapman, Andrew R; Love, Sara A; Schulz, Karen; Cao, Jing; Mills, Nicholas L; Apple, Fred S

2017-01-01

Rapid rule-out strategies using high-sensitivity cardiac troponin assays are largely supported by studies performed outside the US in selected cohorts of patients with chest pain that are atypical of US practice, and focused exclusively on ruling out acute myocardial infarction (AMI), rather than acute myocardial injury, which is more common and associated with a poor prognosis. Prospective, observational study of consecutive patients presenting to emergency departments [derivation (n = 1647) and validation (n = 2198) cohorts], where high-sensitivity cardiac troponin I (hs-cTnI) was measured on clinical indication. The negative predictive value (NPV) and diagnostic sensitivity of an hs-cTnI concentration

Short delay in timing of emergence determines establishment success in Pinus sylvestris across microhabitats.

PubMed

Castro, Jorge

2006-12-01

The date of emergence may have far-reaching implications for seedling performance. Seedlings emerging early in the growing season often have a greater rate of survival or grow better if early emergence provides advantages with respect to an environmental cue. As a result, the benefits of early emergence may be lost if the environmental stress creating the differences among cohorts disappears. The experimental manipulation under field conditions of the factors that constitute the main sources of stress for seedling establishment is thus a straightforward method to evaluate the impact of date of emergence on seedling establishment under realistic conditions. Two field experiments were performed to analyse the effect of emergence date on survival and first-year growth of Scots pine seedlings in natural mountain forests in south-east Spain. Two main environmental factors that determine seedling success in these mountains were considered: (1) microhabitat type (monitoring the effect of date of emergence in the three most common microhabitats where seedlings recruit); (2) summer drought (monitored by an irrigation treatment with control and watered sampling points). Overall, early emergence resulted in a higher probability of survival and better growth in the two experiments and across microhabitats. However, the reduction in summer drought did not diminish the differences observed among cohorts: all cohorts increased their survival and growth, but early cohorts still had a clear advantage. Date of emergence determines establishment success of Pinus sylvestris seedlings, even if cohorts are separated by only a few days, irrespective of the intensity of summer drought. The experimental design, covering a gradient of light intensity and soil moisture that simulates conditions of the regeneration niche of Scots pine across its geographical range, allows the results to be extrapolated to other areas of the species. Date of emergence is thus likely to have a large impact on the demography of Scots pine across its geographical range.