Comparison of sexual behavior and HIV risk between two HIV-1 serodiscordant couple cohorts: the CHAVI 002 study.

PubMed

Ritchie, Adam J; Kuldanek, Kristin; Moodie, Zoe; Wang, Z Maggie; Fox, Julie; Nsubuga, Rebecca N; Legg, Kenneth; Birabwa, Esther F; Kaleebu, Pontiano; McMichael, Andrew J; Watera, Christine; Goonetilleke, Nilu; Fidler, Sarah

2012-01-01

The CHAVI002 study was designed to characterize immune responses, particularly HIV-specific T-cell responses, amongst 2 cohorts of HIV-exposed seronegative (HESN) individuals. The absence of a clear definition of HESNs has impaired comparison of research within and between such cohorts. This report describes two distinct HESN cohorts and attempts to quantify HIV exposure using a 'HIV risk index' (RI) model. HIV serodiscordant couples (UK; 24, Uganda; 72) and HIV unexposed seronegative (HUSN) controls (UK; 14, Uganda; 26 couples, 3 individuals) completed sexual behavior questionnaires every 3 months over a 9 month period. The two cohorts were heterogeneous, with most HESNs in the UK men who have sex with men (MSM), while all HESNs in Uganda were in heterosexual relationships. Concordance of responses between partners was determined. Each participant's sexual behavior score (SBS) was estimated based on the number and type of unprotected sex acts carried out in defined time periods. Independent HIV acquisition risk factors (partner plasma viral load, STIs, male circumcision, pregnancy) were integrated with the SBS, generating a RI for each HESN. 96 HIV serodiscordant couples completed 929 SBQs. SBSs remained relatively stable amongst the UK cohort, whilst decreasing from Visit 1 to 2 in the Ugandan cohort. Compared to the Ugandan cohort, SBSs and RIs in the UK cohort were lower at visit 1, and generally higher at later visits. Differences between the cohorts, with lower rates of ART use in Uganda and higher risk per-act sex in the UK, had major impacts on the SBSs and RIs of each cohort. There was one HIV transmission event in the UK cohort. Employment of a risk quantification model facilitated quantification and comparison of HIV acquisition risk across two disparate HIV serodiscordant couple cohorts.

Cohort Changes in Attitudes About Legalized Abortion.

ERIC Educational Resources Information Center

Cutler, Stephen J.; And Others

Cohort changes in attitudes about the availability of legal abortions are traced over a 12-year period using data from seven national surveys. Contrary to the aging-conservatism hypothesis, trends in the direction of increasingly favorable attitudes between 1965 and 1973 and general stability thereafter characterize all cohorts. On this issue,…

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.

Alcohol-Related Diagnoses in Hospital Admissions for All Causes Among Middle-Aged and Older Adults: Trends and Cohort Differences From 1993 to 2010.

PubMed

Sacco, Paul; Unick, George Jay; Kuerbis, Alexis; Koru, A Güneş; Moore, Alison A

2015-12-01

This aim of this study was to characterize trends in alcohol-related hospital admissions among middle-aged and older adults from 1993 to 2010 in relation to age, gender, race, and cohort membership. This study utilized repeated cross-sectional data from the Nationwide Inpatient Sample. Using alcohol-related classified admissions, yearly rates and longitudinal trends of alcohol-related inpatient hospitalizations based on age, period, birth cohort, gender, and race were estimated. Among those aged 45 and older, admissions rose from an estimated 610,634 to more than 1,134,876, and rates of any alcohol-related diagnosis also increased from 1993 to 2010. Rates for men were consistently higher than women, and rates for Blacks were higher than Whites. Age was associated with decreasing rates, but post-World War II cohorts displayed higher rates over time. Rates of alcohol-related admissions are increasing among adults above age 45, which may be a function of cohort effects. Training the health care workforce is crucial to respond to this trend. © The Author(s) 2015.

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

PubMed

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

2017-12-28

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

Cohort profile: the Western Australian Sleep Health Study.

PubMed

Mukherjee, Sutapa; Hillman, David; Lee, Jessica; Fedson, Annette; Simpson, Laila; Ward, Kim; Love, Gregory; Edwards, Cass; Szegner, Bernadett; Palmer, Lyle John

2012-03-01

Epidemiologic and genetic studies of obstructive sleep apnoea (OSA) are limited by a lack of large-scale, well-characterized OSA cohorts. These studies require large sample size to provide adequate power to detect differences between groups. This study describes the development of such a cohort (The Western Australian Sleep Health Study) in OSA patients of Caucasian-European origin attending the only public sleep clinic in Western Australia (WA). The main aim of the study is to phenotype 4,000 OSA patients in order to define the genetics of OSA and its co-morbidities. Almost all underwent laboratory-based attended polysomnography (PSG). Currently complete data (questionnaire, biochemistry, DNA, and PSG) has been obtained on over 3,000 individuals and will reach the target of 4,000 individuals by the end of 2010. In a separate but related study, we have developed a sleep study database containing data from all patients who have undergone PSG at the sleep laboratory since its inception in 1988 until the present day (over 30,000 PSG studies representing data from approximately 20,000 individuals). In addition, data from both cohorts have been linked prospectively to statutory health data collected by the WA Department of Health. This study will be the largest sleep clinic cohort database internationally with access to genetic and epidemiological data. It is unique among sleep clinic cohorts because of its size, the breadth of data collected and the ability to link prospectively to statutory health data. It will be a major tool to comprehensively assess genetic and epidemiologic factors determining OSA and its co-morbidities.

Development in Children with Achondroplasia: A Prospective Clinical Cohort Study

ERIC Educational Resources Information Center

Ireland, Penelope J.; Donaghey, Samantha; McGill, James; Zankl, Andreas; Ware, Robert S.; Pacey, Verity; Ault, Jenny; Savarirayan, Ravi; Sillence, David; Thompson, Elizabeth; Townshend, Sharron; Johnston, Leanne M.

2012-01-01

Aim: Achondroplasia is characterized by delays in the development of communication and motor skills. While previously reported developmental profiles exist across gross motor, fine motor, feeding, and communication skills, there has been no prospective study of development across multiple areas simultaneously. Method: This Australasian…

Creatine Transporter Deficiency: Screening of Males with Neurodevelopmental Disorders and Neurocognitive Characterization of a Case.

PubMed

Thurm, Audrey; Himelstein, Daniel; DʼSouza, Precilla; Rennert, Owen; Jiang, Susanqi; Olatunji, Damilola; Longo, Nicola; Pasquali, Marzia; Swedo, Susan; Salomons, Gajja S; Carrillo, Nuria

2016-05-01

Creatine transporter deficiency (CTD) is an X-linked, neurometabolic disorder associated with intellectual disability that is characterized by brain creatine (Cr) deficiency and caused by mutations in SLC6A8, the Cr transporter 1 protein gene. CTD is identified by elevated urine creatine/creatinine (Cr/Crn) ratio or reduced Cr peak on brain magnetic resonance spectroscopy; the diagnosis is confirmed by decreased Cr uptake in cultured fibroblasts, and/or identification of a mutation in the SLC6A8 gene. Prevalence studies suggest this disorder may be underdiagnosed. We sought to identify cases from a well-characterized cohort of children diagnosed with neurodevelopmental disorders. Urine screening for CTD was performed on a cohort of 46 males with autism spectrum disorder (ASD) and 9 males with a history of non-ASD developmental delay (DD) classified with intellectual disability. We identified 1 patient with CTD in the cohort based on abnormal urine Cr/Crn, and confirmed the diagnosis by the identification of a novel frameshift mutation in the SLC6A8 gene. This patient presented without ASD but with intellectual disability, and was characterized by a nonspecific phenotype of early language delay and DD that persisted into moderate-to-severe intellectual disability, consistent with previous descriptions of CTD. Identification of patients with CTD is possible by measuring urine Cr and Crn levels and the current case adds to the growing literature of neurocognitive deficits associated with the disorder that affect cognition, language and behavior in childhood.

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

PubMed

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

2018-01-01

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

Linking Investigations in Trauma and Emergency Services (LITES)

DTIC Science & Technology

2017-10-01

observational cohort that will have a limited data set from trauma registry data and electronic health records. Specific Aim one is to characterize the...epidemiology of moderate and severe physical injury in the U.S. and across the LITES network and investigate regional variations of presenting...observational cohort that will have a limited data set from trauma registry data and electronic health records. Specific Aim one is to characterize the

Decreased graft survival in liver transplant recipients of donors with positive blood cultures: a review of the United Network for Organ Sharing dataset.

PubMed

Huaman, Moises A; Vilchez, Valery; Mei, Xiaonan; Shah, Malay B; Daily, Michael F; Berger, Jonathan; Gedaly, Roberto

2017-06-01

Liver transplantation using blood culture positive donors (BCPD) has allowed a significant expansion of the donor pool. We aimed to characterize BCPD and assess the outcomes of BCPD liver transplant recipients. We retrieved data from the United Network for Organ Sharing (UNOS) registry on all adults who underwent primary, single-organ deceased-donor liver transplantation in the USA between 2008 and 2013. Patients were classified into two cohorts: the BCPD cohort and the non-BCPD cohort. One-year graft and patient survival were compared between cohorts using Kaplan-Meier estimates and Cox models. A total of 28 961 patients were included. There were 2316 (8.0%) recipients of BCPD. BCPD were more likely to be older, female, black, diabetic, hypertensive, and obese compared to non-BCPD. Graft survival was significantly lower in BCPD recipients compared to non-BCPD recipients (Kaplan-Meier, 0.85 vs. 0.87; P = 0.009). Results remained significant in propensity-matched analysis (P = 0.038). BCPD was independently associated with decreased graft survival (adjusted HR; 1.10, 95% CI 1.01-1.20; P = 0.04). There were no significant differences in patient survival between study groups. BCPD was associated with decreased graft survival in liver transplant recipients. Studies are needed to identify subgroups of BCPD with the highest risk of graft failure and characterize the underlying pathogenic mechanisms. © 2016 Steunstichting ESOT.

Using Satellite Data to Evaluate Linkages Between Land Cover/Land Use and Hypertension in a National Cohort

NASA Technical Reports Server (NTRS)

McClure, Leslie; Crosson, Bill; Al-Hamdan, Mohammed; Estes, Maury; Estes, Sue; Quattrochi, Dale

2009-01-01

Coincident with global expansion of urban areas has been an increase in hypertension. It is unclear how much the urban environment contributes as a risk factor for blood pressure differences, and how much is due to a variety of environmental, lifestyle, and demographic correlates of urbanization. Objectives/Purpose: The purpose of this study is to examine the relationship between living environment (defined as urban, suburban, or rural) and hypertension in selected regions from the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. Methods: REGARDS is a national cohort of 30,228 participants from the 48 contiguous United States. We used data from 4 metropolitan regions (Philadelphia, Atlanta, Minneapolis and Chicago) for this study (n=3928). We used Land Cover/Land Use (LCLU) information from the 30-meter National Land Cover Data. Results: Overall, 1996 (61%) of the participants were hypertensive. We characterized participants into urban, suburban or rural living environments using the LCLU data. In univariate models, we found that living environment is associated with hypertension, but that after adjustment for known hypertension risk factors, the relationship was no longer present at the 95% confidence level. Conclusions: LCLU data can be utilized to characterize the living environment, which in turn can be applied to studies of public health outcomes. Further study regarding the relationship between hypertension and living environment should focus on additional characteristics of the associated environment.

Risk factors of significant pain syndrome 90 days after minor thoracic injury: trajectory analysis.

PubMed

Daoust, Raoul; Emond, Marcel; Bergeron, Eric; LeSage, Natalie; Camden, Stéphanie; Guimont, Chantal; Vanier, Laurent; Chauny, Jean-Marc

2013-11-01

The objective was to identify the risk factors of clinically significant pain at 90 days in patients with minor thoracic injury (MTI) discharged from the emergency department (ED). A prospective, multicenter, cohort study was conducted in four Canadian EDs from November 2006 to November 2010. All consecutive patients aged 16 years or older with MTI were eligible at discharge from EDs. They underwent standardized clinical and radiologic evaluations at 1 and 2 weeks, followed by standardized telephone interviews at 30 and 90 days. A pain trajectory model characterized groups of patients with different pain evolutions and ascertained specific risk factors in each group through multivariate analysis. In this cohort of 1,132 patients, 734 were eligible for study inclusion. The authors identified a pain trajectory that characterized 18.2% of the study population experiencing clinically significant pain (>3 of 10) at 90 days after a MTI. Multivariate modeling found two or more rib fractures, smoking, and initial oxygen saturation below 95% to be predictors of this group of patients. To the authors' knowledge, this is the first prospective study of trajectory modeling to detect risk factors associated with significant pain at 90 days after MTI. These factors may help in planning specific treatment strategies and should be validated in another prospective cohort. © 2013 by the Society for Academic Emergency Medicine.

PRIMARY CILIARY DYSKINESIA: DIAGNOSTIC AND PHENOTYPIC FEATURES

EPA Science Inventory

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormalities in ciliary structure/function. We hypothesized that the major clinical and biologic phenotypic markers of the disease could be evaluated by studying a cohort of subjects suspected of having PCD. ...

Clopidogrel treatment on the incidence and severity of community acquired pneumonia in a cohort study and meta-analysis of antiplatelet therapy in pneumonia and critical illness

PubMed Central

Gross, A. Kendall; Dunn, Steven P.; Feola, David J.; Martin, Craig A.; Charnigo, Richard; Li, Zhenyu; Abdel-Latif, Ahmed; Smyth, Susan S.

2013-01-01

Background Platelet activation results in the release and upregulation of mediators responsible for immune cell activation and recruitment, suggesting that platelets play an active role in immunity. Animal models and retrospective data have demonstrated benefit of antiplatelet therapy on inflammatory mediator expression and clinical outcomes. This study sought to characterize effects of clopidogrel on the incidence and severity of community-acquired pneumonia (CAP). Methods A retrospective cohort study was conducted of Kentucky Medicaid patients (2001-2005). The exposed cohort consisted of patients receiving at least six consecutive clopidogrel prescriptions; the non-exposed cohort was comprised of patients not prescribed clopidogrel. Primary endpoints included incidence of CAP and inpatient treatment. Secondary severity endpoints included mortality, intensive care unit admission, mechanical ventilation, sepsis, and acute respiratory distress syndrome/acute lung injury. Results CAP incidence was significantly greater in the exposed cohort (OR 3.39, 95% CI 3.27-3.51, p < 0.0001) that remained after adjustment (OR 1.48, 95% CI 1.41-1.55, p < 0.0001). Inpatient treatment was more common in the exposed cohort (OR 1.96, 95% CI 1.85-2.07, p < 0.0001), but no significant difference remained after adjustment. Trends favoring the exposed cohort were found for the secondary severity endpoints of mechanical ventilation (p = 0.07) and mortality (p = 0.10). Pooled analysis of published studies supports these findings. Conclusions While clopidogrel use may be associated with increased CAP incidence, clopidogrel does not appear to increase – and may reduce – its severity among inpatients. Because this study was retrospective and could not quantify all variables (e.g., aspirin use), these findings should be explored prospectively. PMID:23124575

The Canadian HIV and aging cohort study - determinants of increased risk of cardio-vascular diseases in HIV-infected individuals: rationale and study protocol.

PubMed

Durand, Madeleine; Chartrand-Lefebvre, Carl; Baril, Jean-Guy; Trottier, Sylvie; Trottier, Benoit; Harris, Marianne; Walmsley, Sharon; Conway, Brian; Wong, Alexander; Routy, Jean-Pierre; Kovacs, Colin; MacPherson, Paul A; Monteith, Kenneth Marc; Mansour, Samer; Thanassoulis, George; Abrahamowicz, Michal; Zhu, Zhitong; Tsoukas, Christos; Ancuta, Petronela; Bernard, Nicole; Tremblay, Cécile L

2017-09-11

With potent antiretroviral drugs, HIV infection is becoming a chronic disease. Emergence of comorbidities, particularly cardiovascular disease (CVD) has become a leading concern for patients living with the infection. We hypothesized that the chronic and persistent inflammation and immune activation associated with HIV disease leads to accelerated aging, characterized by CVD. This will translate into higher incidence rates of CVD in HIV infected participants, when compared to HIV negative participants, after adjustment for traditional CVD risk factors. When characterized further using cardiovascular imaging, biomarkers, immunological and genetic profiles, CVD associated with HIV will show different characteristics compared to CVD in HIV-negative individuals. The Canadian HIV and Aging cohort is a prospective, controlled cohort study funded by the Canadian Institutes of Health Research. It will recruit patients living with HIV who are aged 40 years or older or have lived with HIV for 15 years or more. A control population, frequency matched for age, sex, and smoking status, will be recruited from the general population. Patients will attend study visits at baseline, year 1, 2, 5 and 8. At each study visit, data on complete medical and pharmaceutical history will be captured, along with anthropometric measures, a complete physical examination, routine blood tests and electrocardiogram. Consenting participants will also contribute blood samples to a research biobank. The primary outcome is incidence of a composite of: myocardial infarction, coronary revascularization, stroke, hospitalization for angina or congestive heart failure, revascularization or amputation for peripheral artery disease, or cardiovascular death. Preplanned secondary outcomes are all-cause mortality, incidence of the metabolic syndrome, incidence of type 2 diabetes, incidence of renal failure, incidence of abnormal bone mineral density and body fat distribution. Patients participating to the cohort will be eligible to be enrolled in four pre-planned sub-studies of cardiovascular imaging, glucose metabolism, immunological and genetic risk profile. The Canadian HIV and Aging Cohort will provide insights on pathophysiological pathways leading to premature CVD for patients living with HIV.

Characterization of a Clinician-Scientist Cohort in Ophthalmology: A Demographic Analysis of K Grant Awardees in Ophthalmology

PubMed Central

Chao, Daniel L.; Schiffman, Joyce C.; Gedde, Steven J.

2013-01-01

Objective To analyze ophthalmologists who are National Institutes of Health (NIH) K grant awardees to characterize clinician-scientists in ophthalmology. Design Cohort study. Participants Ophthalmologists who have received a K award from 1996 to 2010. Methods K08 and K23 grant awardees were identified through the NIH Research Portfolio Online Reporter database. Information including gender, institution, educational degrees, and success in obtaining an R01 grant was analyzed. Main Outcome Measure Receipt of an R01 grant. Results One hundred five ophthalmologists were identified who received K08 or K23 grants from the National Eye Institute from 1996 to 2010. Overall, 75% of these were male, although 43% of K awardees were women from 2006 to 2010. Sixty five percent (68/105) of individuals came from ophthalmology departments that ranked in the top 20 of NIH funding in 2010. The most predominant subspecialties represented were retina (32%), cornea (22%), and glaucoma (15%). Among the K awardees, 40% (42/105) had a Doctor of Philosophy (PhD) degree in addition to their Medical Doctor (MD) degree. From 1996 to 2000, 61% (23/38) individuals were successful in obtaining an R01 grant, while only 13% (5/39) individuals from 2001 to 2005 have obtained R01 grants (p<0.001). Conclusions Gender disparities exist among K awardees in ophthalmology, but these seem to be improving over time. None of the other variables studied: gender, PhD degree, specialty, or funding tier was associated with obtaining R01 funding. This study helps to characterize the clinician-scientist cohort in ophthalmology and identify areas to improve the recruitment of these individuals. PMID:23631948

Characterization of a clinician-scientist cohort in ophthalmology: a demographic analysis of k grant awardees in ophthalmology.

PubMed

Chao, Daniel L; Schiffman, Joyce C; Gedde, Steven J

2013-10-01

To analyze ophthalmologists who are National Institutes of Health (NIH) K grant awardees to characterize clinician-scientists in ophthalmology. Cohort study. Ophthalmologists who have received a K award from 1996 through 2010. K08 and K23 grant awardees were identified through the NIH Research Portfolio Online Reporter database. Information including gender, institution, educational degrees, and success in obtaining an R01 grant was analyzed. Receipt of an R01 grant. One hundred five ophthalmologists were identified who received K08 or K23 grants from the National Eye Institute from 1996 through 2010. Overall, 75% of these were male, although 43% of K awardees were women from 2006 through 2010. Sixty-five percent (68/105) of individuals came from ophthalmology departments that ranked in the top 20 of NIH funding in 2010. The most predominant subspecialties represented were retina (32%), cornea (22%), and glaucoma (15%). Among the K awardees, 40% (42/105) had a doctor of philosophy (PhD) degree in addition to their medical doctor degree. From 1996 through 2000, 61% (23/38) were successful in obtaining an R01 grant, whereas only 13% (5/39) from 2001 through 2005 obtained R01 grants (P<0.001). Gender disparities exist among K awardees in ophthalmology, but these seem to be improving over time. None of the other variables studied-gender, PhD degree, specialty, or funding tier-was associated with obtaining R01 funding. This study helps to characterize the clinician-scientist cohort in ophthalmology and to identify areas to improve the recruitment of these individuals. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

ANALYSIS OF COMPONENTS OF PARTICULATE MATTER (PM2.5) FOR AN EXPOSURE ASSESSMENT STUDY OF TWO SENSITIVE COHORTS IN ATLANTA, GA

EPA Science Inventory

Introduction
An exposure assessment study was conducted in Atlanta, GA during fall 1999 and spring 2000 to examine the short-term effects of exposure to particulate matter and gaseous air pollutants on heart rate variability (HRV). Characterization of particulate matter (PM...

Stability and Volatility of STEM Career Interest in High School: A Gender Study

ERIC Educational Resources Information Center

Sadler, Philip M.; Sonnert, Gerhard; Hazari, Zahra; Tai, Robert

2012-01-01

This retrospective cohort study characterizes how interest in science, technology, engineering, mathematics (STEM) careers changes during high school for more than 6,000 students in a representative national sample of 34 two- and four-year colleges taking mandatory college English courses. Overall, large gender differences in career plans were…

Correlates of Identity Configurations: Three Studies with Adolescent and Emerging Adult Cohorts

ERIC Educational Resources Information Center

Crocetti, Elisabetta; Scrignaro, Marta; Sica, Luigia Simona; Magrin, Maria Elena

2012-01-01

Adolescence and emerging adulthood are two core developmental periods in which individuals can develop a meaningful identity across domains. However, there is a lack of studies exploring correlates of different identity configurations. The purpose of this article was to fill this gap in examining correlates of configurations characterized by…

Effects of fat mass on motor development during the first two years of life

USDA-ARS?s Scientific Manuscript database

Objective: This study characterized total body fat mass and motor development during the first two years of life in healthy infants. Design: Participants (N=469) from the Beginnings’ cohort, a prospective, longitudinal study of early infant feeding, were assessed at 3, 6, 9, 12 and 24 months of age...

Gene expression profiling at birth characterizing the preterm infant with early onset infection.

PubMed

Hilgendorff, Anne; Windhorst, Anita; Klein, Manuel; Tchatalbachev, Svetlin; Windemuth-Kieselbach, Christine; Kreuder, Joachim; Heckmann, Matthias; Gkatzoflia, Anna; Ehrhardt, Harald; Mysliwietz, Josef; Maier, Michael; Izar, Benjamin; Billion, Andre; Gortner, Ludwig; Chakraborty, Trinad; Hossain, Hamid

2017-02-01

Early onset infection (EOI) in preterm infants <32 weeks gestational age (GA) is associated with a high mortality rate and the development of severe acute and long-term complications. The pathophysiology of EOI is not fully understood and clinical and laboratory signs of early onset infections in this patient cohort are often not conclusive. Thus, the aim of this study was to identify signatures characterizing preterm infants with EOI by using genome-wide gene expression (GWGE) analyses from umbilical arterial blood of preterm infants. This prospective cohort study was conducted in preterm infants <32 weeks GA. GWGE analyses using CodeLink human microarrays were performed from umbilical arterial blood of preterm infants with and without EOI. GWGE analyses revealed differential expression of 292 genes in preterm infants with EOI as compared to infants without EOI. Infants with EOI could be further differentiated into two subclasses and were distinguished by the magnitude of the expression of genes involved in both neutrophil and T cell activation. A hallmark activity for both subclasses of EOI was a common suppression of genes involved in natural killer (NK) cell function, which was independent from NK cell numbers. Significant results were recapitulated in an independent validation cohort. Gene expression profiling may enable early and more precise diagnosis of EOI in preterm infants. Gene expression (GE) profiling at birth characterizes preterm infants with EOI. GE analysis indicates dysregulation of NK cell activity. NK cell activity at birth may be a useful marker to improve early diagnosis of EOI.

Rationale of the FIBROTARGETS study designed to identify novel biomarkers of myocardial fibrosis

PubMed Central

Ferreira, João Pedro; Machu, Jean‐Loup; Girerd, Nicolas; Jaisser, Frederic; Thum, Thomas; Butler, Javed; González, Arantxa; Diez, Javier; Heymans, Stephane; McDonald, Kenneth; Gyöngyösi, Mariann; Firat, Hueseyin; Rossignol, Patrick; Pizard, Anne

2017-01-01

Abstract Aims Myocardial fibrosis alters the cardiac architecture favouring the development of cardiac dysfunction, including arrhythmias and heart failure. Reducing myocardial fibrosis may improve outcomes through the targeted diagnosis and treatment of emerging fibrotic pathways. The European‐Commission‐funded ‘FIBROTARGETS’ is a multinational academic and industrial consortium with the main aims of (i) characterizing novel key mechanistic pathways involved in the metabolism of fibrillary collagen that may serve as biotargets, (ii) evaluating the potential anti‐fibrotic properties of novel or repurposed molecules interfering with the newly identified biotargets, and (iii) characterizing bioprofiles based on distinct mechanistic phenotypes involving the aforementioned biotargets. These pathways will be explored by performing a systematic and collaborative search for mechanisms and targets of myocardial fibrosis. These mechanisms will then be translated into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure. Methods and results The FIBROTARGETS consortium has merged data from 12 patient cohorts in a common database available to individual consortium partners. The database consists of >12 000 patients with a large spectrum of cardiovascular clinical phenotypes. It integrates community‐based population cohorts, cardiovascular risk cohorts, and heart failure cohorts. Conclusions The FIBROTARGETS biomarker programme is aimed at exploring fibrotic pathways allowing the bioprofiling of patients into specific ‘fibrotic’ phenotypes and identifying new therapeutic targets that will potentially enable the development of novel and tailored anti‐fibrotic therapies for heart failure. PMID:28988439

MicroRNA-150 Is up-regulated in extranodal marginal zone lymphoma of MALT type.

PubMed

Gebauer, Niklas; Kuba, Johannes; Senft, Andrea; Schillert, Arne; Bernard, Veronica; Thorns, Christoph

2014-01-01

The mechanisms promoting malignant transformation from chronic Helicobacter pylori-gastritis to gastric extranodal marginal zone lymphoma (MALT lymphoma) are insufficiently characterized. This follow-up study aimed to validate candidate microRNAs (miRs) in the process of neoplastic transformation. MicroRNA expression signatures (n=20) were generated for a total of 60 cases of gastric lesions ranging from Wotherspoon 0-5 employing a quantitative real-time polymerase chain reaction (PCR) approach. Morphological and immunohistochemical characterization of the cohort was supplemented by PCR-based immunoglobulin heavy chain recombination studies. Quantitative expression of miR-150, miR-142.3p, miR-375 and miR-494 was significantly de-regulated in samples from MALT lymphoma compared to those from gastritis. The previously reported up-regulation of miR-150 in marginal zone lymphoma of MALT type was verified in an independent cohort of lymphoma samples employing a modified methodology. This further substantiates the role of miR-150 as a potential oncomiR in MALT lymphoma.

Systems Biology Methods for Alzheimer's Disease Research Toward Molecular Signatures, Subtypes, and Stages and Precision Medicine: Application in Cohort Studies and Trials.

PubMed

Castrillo, Juan I; Lista, Simone; Hampel, Harald; Ritchie, Craig W

2018-01-01

Alzheimer's disease (AD) is a complex multifactorial disease, involving a combination of genomic, interactome, and environmental factors, with essential participation of (a) intrinsic genomic susceptibility and (b) a constant dynamic interplay between impaired pathways and central homeostatic networks of nerve cells. The proper investigation of the complexity of AD requires new holistic systems-level approaches, at both the experimental and computational level. Systems biology methods offer the potential to unveil new fundamental insights, basic mechanisms, and networks and their interplay. These may lead to the characterization of mechanism-based molecular signatures, and AD hallmarks at the earliest molecular and cellular levels (and beyond), for characterization of AD subtypes and stages, toward targeted interventions according to the evolving precision medicine paradigm. In this work, an update on advanced systems biology methods and strategies for holistic studies of multifactorial diseases-particularly AD-is presented. This includes next-generation genomics, neuroimaging and multi-omics methods, experimental and computational approaches, relevant disease models, and latest genome editing and single-cell technologies. Their progressive incorporation into basic research, cohort studies, and trials is beginning to provide novel insights into AD essential mechanisms, molecular signatures, and markers toward mechanism-based classification and staging, and tailored interventions. Selected methods which can be applied in cohort studies and trials, with the European Prevention of Alzheimer's Dementia (EPAD) project as a reference example, are presented and discussed.

Do Stem Taper Microgrooves Influence Taper Corrosion in Total Hip Arthroplasty? A Matched Cohort Retrieval Study.

PubMed

Arnholt, Christina M; MacDonald, Daniel W; Underwood, Richard J; Guyer, Eric P; Rimnac, Clare M; Kurtz, Steven M; Mont, Michael A; Klein, Gregg R; Lee, Gwo-Chin; Chen, Antonia F; Hamlin, Brian R; Cates, Harold E; Malkani, Arthur L; Kraay, Matthew J

2017-04-01

Previous studies identified imprinting of the stem morphology onto the interior head bore, leading researchers to hypothesize an influence of taper topography on mechanically assisted crevice corrosion. The purpose of this study was to analyze whether microgrooved stem tapers result in greater fretting corrosion damage than smooth stem tapers. A matched cohort of 120 retrieved head-stem pairs from metal-on-polyethylene bearings was created controlling for implantation time, flexural rigidity, apparent length of engagement, and head size. There were 2 groups of 60 heads each, mated with either smooth or microgrooved stem tapers. A high-precision roundness machine was used to measure and categorize the surface morphology. Fretting corrosion damage at the head-neck junction was characterized using the Higgs-Goldberg scoring method. Fourteen of the most damaged heads were analyzed for the maximum depth of material loss and focused ion beam cross-sectioned to view oxide and base metal. Fretting corrosion damage was not different between the 2 cohorts at the femoral head (P = .14, Mann-Whitney) or stem tapers (P = .35). There was no difference in the maximum depths of material loss between the cohorts (P = .71). Cross-sectioning revealed contact damage, signs of micro-motion, and chromium-rich oxide layers in both cohorts. Microgroove imprinting did not appear to have a different effect on the fretting corrosion behavior. The results of this matched cohort retrieval study do not support the hypothesis that taper surfaces with microgrooved stems exhibit increased in vivo fretting corrosion damage or material release. Copyright © 2016 Elsevier Inc. All rights reserved.

What's in a Name? The Incorrect Use of Case Series as a Study Design Label in Studies Involving Dogs and Cats.

PubMed

Sargeant, J M; O'Connor, A M; Cullen, J N; Makielski, K M; Jones-Bitton, A

2017-07-01

Study design labels are used to identify relevant literature to address specific clinical and research questions and to aid in evaluating the evidentiary value of research. Evidence from the human healthcare literature indicates that the label "case series" may be used inconsistently and inappropriately. Our primary objective was to determine the proportion of studies in the canine and feline veterinary literature labeled as case series that actually corresponded to descriptive cohort studies, population-based cohort studies, or other study designs. Our secondary objective was to identify the proportion of case series in which potentially inappropriate inferential statements were made. Descriptive evaluation of published literature. One-hundred published studies (from 19 journals) labeled as case series. Studies were identified by a structured literature search, with random selection of 100 studies from the relevant citations. Two reviewers independently characterized each study, with disagreements resolved by consensus. Of the 100 studies, 16 were case series. The remaining studies were descriptive cohort studies (35), population-based cohort studies (36), or other observational or experimental study designs (13). Almost half (48.8%) of the case series or descriptive cohort studies, with no control group and no formal statistical analysis, included inferential statements about the efficacy of treatment or statistical significance of potential risk factors. Authors, peer-reviewers, and editors should carefully consider the design elements of a study to accurately identify and label the study design. Doing so will facilitate an understanding of the evidentiary value of the results. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Physical and Social Contexts of Physical Activity Behaviors of Fifth and Seventh Grade Youth

ERIC Educational Resources Information Center

Saunders, Ruth P.; Dowda, Marsha; Mciver, Kerry; McDonald, Samantha M.; Pate, Russell R.

2018-01-01

Background: The purpose of this study was to characterize the temporal, social, and physical contexts for physical activities commonly reported in a diverse cohort of 753 boys and girls from fifth to seventh grade. Methods: Data were obtained from a multilevel longitudinal study, the Transitions and Activity Changes in Kids. The Physical Activity…

Association of genetic variants of GRIN2B with autism.

PubMed

Pan, Yongcheng; Chen, Jingjing; Guo, Hui; Ou, Jianjun; Peng, Yu; Liu, Qiong; Shen, Yidong; Shi, Lijuan; Liu, Yalan; Xiong, Zhimin; Zhu, Tengfei; Luo, Sanchuan; Hu, Zhengmao; Zhao, Jingping; Xia, Kun

2015-02-06

Autism (MIM 209850) is a complex neurodevelopmental disorder characterized by social communication impairments and restricted repetitive behaviors. It has a high heritability, although much remains unclear. To evaluate genetic variants of GRIN2B in autism etiology, we performed a system association study of common and rare variants of GRIN2B and autism in cohorts from a Chinese population, involving a total sample of 1,945 subjects. Meta-analysis of a triad family cohort and a case-control cohort identified significant associations of multiple common variants and autism risk (Pmin = 1.73 × 10(-4)). Significantly, the haplotype involved with the top common variants also showed significant association (P = 1.78 × 10(-6)). Sanger sequencing of 275 probands from a triad cohort identified several variants in coding regions, including four common variants and seven rare variants. Two of the common coding variants were located in the autism-related linkage disequilibrium (LD) block, and both were significantly associated with autism (P < 9 × 10(-3)) using an independent control cohort. Burden analysis and case-only analysis of rare coding variants identified by Sanger sequencing did not find this association. Our study for the first time reveals that common variants and related haplotypes of GRIN2B are associated with autism risk.

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

PubMed

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

2008-05-01

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

Prevalence and characteristics of Shiga toxin-producing Escherichia coli in finishing pigs: Implications on public health.

PubMed

Cha, Wonhee; Fratamico, Pina M; Ruth, Leah E; Bowman, Andrew S; Nolting, Jacqueline M; Manning, Shannon D; Funk, Julie A

2018-01-02

Shiga toxin-producing Escherichia coli (STEC) are important food-borne pathogens, which can cause serious illnesses, including hemorrhagic colitis and hemolytic uremic syndrome. To study the epidemiology of STEC in finishing pigs and examine the potential risks they pose for human STEC infections, we conducted a longitudinal cohort study in three finishing sites. Six cohorts of pigs (2 cohorts/site, 20 pigs/cohort) were randomly selected, and fecal samples (n=898) were collected every two weeks through their finishing period. Eighty-two pigs (68.3%) shed STEC at least once, and the proportion of STEC-positive pigs varied across sites (50-97.5%) and cohorts (15-100%). Clinically important serotypes, O157:H7 (stx 2c , eae) and O26:H11 (stx 1a , eae), were recovered from two pigs at sites C and A, respectively. The most common serotype isolated was O59:H21 (stx 2e ), which was particularly prevalent in site B as it was recovered from all STEC positive pigs (n=39). Each cohort showed different patterns of STEC shedding, which were associated with the prevalent serotype. The median shedding duration of STEC in pigs was 28days, consistent with our prior study. However, among pigs shedding O59:H21 at least once, pigs in cohort B2 had a significantly longer shedding duration of 42days (P<0.05) compared to other cohorts. Stx2e was the most commonly observed stx variant in finishing pigs (93.9%), in accordance with the previous studies. Stx2e has been reported to be significantly associated with edema disease in pigs, however, the pathogenicity in humans warrants further investigations. Nonetheless, our findings affirm that pigs are an important reservoir for human STEC infections, and that the circulating serotypes in a cohort and site management factors may significantly affect the prevalence of STEC. Molecular characterization of STEC isolates and epidemiological studies to identify risk factors for shedding in pigs are strongly warranted to further address the significance to public health and to develop mitigation strategies. Copyright © 2017. Published by Elsevier B.V.

Whole Blood Gene Expression Profiles to Assess Pathogenesis and Disease Severity in Infants with Respiratory Syncytial Virus Infection

PubMed Central

Mejias, Asuncion; Dimo, Blerta; Suarez, Nicolas M.; Garcia, Carla; Suarez-Arrabal, M. Carmen; Jartti, Tuomas; Blankenship, Derek; Jordan-Villegas, Alejandro; Ardura, Monica I.; Xu, Zhaohui; Banchereau, Jacques; Chaussabel, Damien; Ramilo, Octavio

2013-01-01

Background Respiratory syncytial virus (RSV) is the leading cause of viral lower respiratory tract infection (LRTI) and hospitalization in infants. Mostly because of the incomplete understanding of the disease pathogenesis, there is no licensed vaccine, and treatment remains symptomatic. We analyzed whole blood transcriptional profiles to characterize the global host immune response to acute RSV LRTI in infants, to characterize its specificity compared with influenza and human rhinovirus (HRV) LRTI, and to identify biomarkers that can objectively assess RSV disease severity. Methods and Findings This was a prospective observational study over six respiratory seasons including a cohort of infants hospitalized with RSV (n = 135), HRV (n = 30), and influenza (n = 16) LRTI, and healthy age- and sex-matched controls (n = 39). A specific RSV transcriptional profile was identified in whole blood (training cohort, n = 45 infants; Dallas, Texas, US) and validated in three different cohorts (test cohort, n = 46, Dallas, Texas, US; validation cohort A, n = 16, Turku, Finland; validation cohort B, n = 28, Columbus, Ohio, US) with high sensitivity (94% [95% CI 87%–98%]) and specificity (98% [95% CI 88%–99%]). It classified infants with RSV LRTI versus HRV or influenza LRTI with 95% accuracy. The immune dysregulation induced by RSV (overexpression of neutrophil, inflammation, and interferon genes, and suppression of T and B cell genes) persisted beyond the acute disease, and immune dysregulation was greatly impaired in younger infants (<6 mo). We identified a genomic score that significantly correlated with outcomes of care including a clinical disease severity score and, more importantly, length of hospitalization and duration of supplemental O2. Conclusions Blood RNA profiles of infants with RSV LRTI allow specific diagnosis, better understanding of disease pathogenesis, and assessment of disease severity. This study opens new avenues for biomarker discovery and identification of potential therapeutic or preventive targets, and demonstrates that large microarray datasets can be translated into a biologically meaningful context and applied to the clinical setting. Please see later in the article for the Editors' Summary PMID:24265599

[Prognostic differences of phenotypes in pT1-2N0 invasive breast cancer: a large cohort study with cluster analysis].

PubMed

Wang, Z; Wang, W H; Wang, S L; Jin, J; Song, Y W; Liu, Y P; Ren, H; Fang, H; Tang, Y; Chen, B; Qi, S N; Lu, N N; Li, N; Tang, Y; Liu, X F; Yu, Z H; Li, Y X

2016-06-23

To find phenotypic subgroups of patients with pT1-2N0 invasive breast cancer by means of cluster analysis and estimate the prognosis and clinicopathological features of these subgroups. From 1999 to 2013, 4979 patients with pT1-2N0 invasive breast cancer were recruited for hierarchical clustering analysis. Age (≤40, 41-70, 70+ years), size of primary tumor, pathological type, grade of differentiation, microvascular invasion, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) were chosen as distance metric between patients. Hierarchical cluster analysis was performed using Ward's method. Cophenetic correlation coefficient (CPCC) and Spearman correlation coefficient were used to validate clustering structures. The CPCC was 0.603. The Spearman correlation coefficient was 0.617 (P<0.001), which indicated a good fit of hierarchy to the data. A twelve-cluster model seemed to best illustrate our patient cohort. Patients in cluster 5, 9 and 12 had best prognosis and were characterized by age >40 years, smaller primary tumor, lower histologic grade, positive ER and PR status, and mainly negative HER-2. Patients in the cluster 1 and 11 had the worst prognosis, The cluster 1 was characterized by a larger tumor, higher grade and negative ER and PR status, while the cluster 11 was characterized by positive microvascular invasion. Patients in other 7 clusters had a moderate prognosis, and patients in each cluster had distinctive clinicopathological features and recurrent patterns. This study identified distinctive clinicopathologic phenotypes in a large cohort of patients with pT1-2N0 breast cancer through hierarchical clustering and revealed different prognosis. This integrative model may help physicians to make more personalized decisions regarding adjuvant therapy.

Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs

PubMed Central

Kandathil, Abraham J.; Breitwieser, Florian P.; Sachithanandham, Jaiprasath; Robinson, Matthew; Mehta, Shruti H.; Timp, Winston; Salzberg, Steven L.; Thomas, David L.

2017-01-01

Background Next-generation metagenomic sequencing (NGMS) has opened new frontiers in microbial discovery but has been clinically characterized in only a few settings. Objective To explore the plasma virome of persons who inject drugs while characterizing the sensitivity and accuracy of NGMS compared to quantitative clinical standards. Design Longitudinal and cross-sectional studies. Participants Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co-infected persons enrolled in a clinical trial (NCT01285050) and/or a well-characterized cohort study of persons who have injected drugs. Measurements Viral nucleic acid in plasma by NGMS and quantitative polymerase chain reaction (PCR). Results NGMS generated a total of 600 million reads, which included the expected HIV and HCV RNA sequences. HIV and HCV reads were consistently identified only when samples contained >10,000 copies or IU/ml as determined by quantitative PCR. A novel RNA virus, human hepegivirus-1 (HHpgV-1) was also detected by NGMS in 4 samples from 2 persons in the clinical trial. Because of this unexpected finding, using a quantitative PCR assay for HHpgV-1, infection was also detected in 17 (10.9%) of 156 members of a cohort of persons who injected drugs in whom HHpgV-1 viremia persisted for a median of at least 4538 days and was associated with detection of other bloodborne viruses such as HCV RNA and SEN virus D Limitations The medical importance of HHpgV-1infection remains unknown. Conclusions Although NGMS is insensitive to detection of viruses with relatively low plasma nucleic acid concentrations, it may have a broad potential for discovery of new viral infections of potential medical importance like HHpgV-1. PMID:28586923

Metabolic Profiling of Right Ventricular-Pulmonary Vascular Function Reveals Circulating Biomarkers of Pulmonary Hypertension.

PubMed

Lewis, Gregory D; Ngo, Debby; Hemnes, Anna R; Farrell, Laurie; Domos, Carly; Pappagianopoulos, Paul P; Dhakal, Bishnu P; Souza, Amanda; Shi, Xu; Pugh, Meredith E; Beloiartsev, Arkadi; Sinha, Sumita; Clish, Clary B; Gerszten, Robert E

2016-01-19

Pulmonary hypertension and associated right ventricular (RV) dysfunction are important determinants of morbidity and mortality, which are optimally characterized by invasive hemodynamic measurements. This study sought to determine whether metabolite profiling could identify plasma signatures of right ventricular-pulmonary vascular (RV-PV) dysfunction. We measured plasma concentrations of 105 metabolites using targeted mass spectrometry in 71 individuals (discovery cohort) who underwent comprehensive physiological assessment with right-sided heart catheterization and radionuclide ventriculography at rest and during exercise. Our findings were validated in a second cohort undergoing invasive hemodynamic evaluations (n = 71), as well as in an independent cohort with or without known pulmonary arterial (PA) hypertension (n = 30). In the discovery cohort, 21 metabolites were associated with 2 or more hemodynamic indicators of RV-PV function (i.e., resting right atrial pressure, mean PA pressure, pulmonary vascular resistance [PVR], and PVR and PA pressure-flow response [ΔPQ] during exercise). We identified novel associations of RV-PV dysfunction with circulating indoleamine 2,3-dioxygenase (IDO)-dependent tryptophan metabolites (TMs), tricarboxylic acid intermediates, and purine metabolites and confirmed previously described associations with arginine-nitric oxide metabolic pathway constituents. IDO-TM levels were inversely related to RV ejection fraction and were particularly well correlated with exercise PVR and ΔPQ. Multisite sampling demonstrated transpulmonary release of IDO-TMs. IDO-TMs also identified RV-PV dysfunction in a validation cohort with known risk factors for pulmonary hypertension and in patients with established PA hypertension. Metabolic profiling identified reproducible signatures of RV-PV dysfunction, highlighting both new biomarkers and pathways for further functional characterization. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Minimally Invasive Lateral Access Surgery and Reoperation Rates: A Multi-Institution Retrospective Review of 2060 Patients.

PubMed

Nayar, Gautam; Wang, Timothy; Sankey, Eric W; Berry-Candelario, John; Elsamadicy, Aladine A; Back, Adam; Karikari, Isaac; Isaacs, Robert

2018-05-19

Risk factors for surgical revision remain important because of additional readmission, anesthesia, and morbidity for the patient and significant cost for health care systems. Although the rate of reoperation (RRO) is well described for traditional open posterior (OP) approaches, the RRO in minimally invasive lateral (MIL) surgery remains poorly characterized. This study compares the RRO in patients undergoing decompressive lumbar spine surgery via MIL versus OP approaches. Patient demographics and comorbidities were retrospectively collected for 2060 patients undergoing single-stage elective lumbar spinal surgery at multiple institutions. A subset of 1484 patients had long-term data (long-term cohort [LT cohort]). The RRO was compared between approaches through univariate and multivariate analysis. There were 1292 patients (62.7%) who underwent lateral access surgery, whereas 768 patients (37.3%) underwent OP surgery. The MIL cohort was significantly older, had a higher proportion of men, and had more comorbidities than the OP cohort. In the LT cohort, lateral patients were significantly older and had more comorbidities, with a lower body mass index and a lower proportion of men and smokers. Surgical complications between the groups trended to be similar. The MIL cohort had a significantly lower RRO at both 30 days (approximately 57% lower, MIL cohort: 1.01% vs. OP cohort: 2.36%, P = 0.02) and 2 years (approximately 61% lower, MIL cohort: 2.09% vs. OP cohort: 5.37%, P < 0.01) after surgery. On multivariate analysis, surgical approach was the only significant predictor for the RRO at both 30 days (open posterior approach odds ratio [OR], 4.47; 95% confidence interval [CI], 1.33-15.09; P = 0.02) and 2 years (open posterior approach OR, 3.26; 95% CI, 1.26-8.42; P = 0.01). This study shows that MIL surgical approaches, compared with OP approaches, have a significantly lower RRO after lumbar spine surgery. Copyright © 2018 Elsevier Inc. All rights reserved.

Review of the literature on benzene exposure and leukemia subtypes.

PubMed

Schnatter, A Robert; Rosamilia, Kim; Wojcik, Nancy C

2005-05-30

The epidemiologic literature on benzene exposure and leukemia in the MEDLINE and TOXNET databases was examined through October 2004 using the keywords "benzene", "leukemia" and "adverse health effects". This search was complemented by reviewing the reference lists from extant literature reviews and criteria documents on benzene. Published studies were characterized according to the type of industry studied and design, exposure assessment, disease classification, and control for confounding variables. Study design consisted of either cohort studies or case-control studies, which were further categorized into population-based and nested case-control studies. Disease classification considered the source of diagnostic information, whether there was clinical confirmation from medical records or histopathological, morphological and/or cytogenetic reviews, and as to whether the International Classification of Diseases (ICD) or the French-American-British (FAB) schemes were used (no studies used the Revised European-American Lymphoma (REAL) classification scheme). Nine cohort and 13 case-control studies met inclusion criteria for this review. High and significant acute myeloid leukemia risks with positive dose response relationships were identified across study designs, particularly in the "well-conducted" cohort studies and especially in more highly exposed workers in rubber, shoe, and paint industries. Risks for chronic lymphocytic leukemia (CLL) tended to show elevations in nested case-control studies, with possible dose response relationships in at least two of the three studies. However, cohort studies on CLL show no such risks. Data for chronic myeloid leukemia and acute lymphocytic leukemia are sparse and inconclusive.

Characterization of perineural invasion as a component of colorectal cancer staging.

PubMed

Ueno, Hideki; Shirouzu, Kazuo; Eishi, Yoshinobu; Yamada, Kazutaka; Kusumi, Takaya; Kushima, Ryoji; Ikegami, Masahiro; Murata, Akihiko; Okuno, Kiyotaka; Sato, Toshihiko; Ajioka, Yoichi; Ochiai, Atsushi; Shimazaki, Hideyuki; Nakamura, Takahiro; Kawachi, Hiroshi; Kojima, Motohiro; Akagi, Yoshito; Sugihara, Kenichi

2013-10-01

Perineural invasion (PN) in colorectal cancer (CRC) is a site-specific prognostic marker, as mentioned by the AJCC Cancer Staging Manual, but it remains to be clearly defined. We aimed to identify an optimal characterization of PN as a component of cancer staging. On the basis of the anatomic features of the nervous system of the large bowel, site-specific pathologic criteria were assigned to PN according to the location of PN. Multi-institutional pathologic review based on these criteria was performed for 962 patients with stage I to III CRC at 2 institutions (1999 to 2004, cohort 1) and 1883 patients from 8 other institutions (2000 to 2004, cohort 2). In cohort 1, intramural and extramural PN were observed in 152 and 101 patients, respectively, which had a different impact on disease-free survival (hazard ratio, 2.6 [1.9 to 3.5] vs. 4.7 [3.4 to 6.5], respectively). A 3-tiered grading system (Pn0; Pn1a, intramural PN; Pn1b, extramural PN) distinguished 5-year disease-free survival as 88%, 70%, and 48%, respectively; and multivariate analysis identified PN grade as a significant prognostic marker independent of T or N stage. These results were similar in cohort 2. Interinstitutional difference of the prognostic impact of PN grade was acceptably small among all institutions. Interobserver study among 6 gastrointestinal pathologists showed superior judgment reproducibility for PN compared with vascular invasion. The results of our study indicate that PN is an important prognostic marker in CRC. The value of cancer staging could be enhanced by PN assessment using site-specific criteria and a simple grading system based on PN location within the bowel.

Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort

PubMed Central

Banda, Yambazi; Kvale, Mark N.; Hoffmann, Thomas J.; Hesselson, Stephanie E.; Ranatunga, Dilrini; Tang, Hua; Sabatti, Chiara; Croen, Lisa A.; Dispensa, Brad P.; Henderson, Mary; Iribarren, Carlos; Jorgenson, Eric; Kushi, Lawrence H.; Ludwig, Dana; Olberg, Diane; Quesenberry, Charles P.; Rowell, Sarah; Sadler, Marianne; Sakoda, Lori C.; Sciortino, Stanley; Shen, Ling; Smethurst, David; Somkin, Carol P.; Van Den Eeden, Stephen K.; Walter, Lawrence; Whitmer, Rachel A.; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil

2015-01-01

Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. Principal component (PC) and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed, considering only nonadjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian–European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3741 genetically identified parent–child pairs, 93% were concordant for self-reported race/ethnicity; among 2018 genetically identified full-sib pairs, 96% were concordant; the lower rate for parent–child pairs was largely due to intermarriage. The parent–child pairs revealed a trend toward increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies. PMID:26092716

Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort.

PubMed

Banda, Yambazi; Kvale, Mark N; Hoffmann, Thomas J; Hesselson, Stephanie E; Ranatunga, Dilrini; Tang, Hua; Sabatti, Chiara; Croen, Lisa A; Dispensa, Brad P; Henderson, Mary; Iribarren, Carlos; Jorgenson, Eric; Kushi, Lawrence H; Ludwig, Dana; Olberg, Diane; Quesenberry, Charles P; Rowell, Sarah; Sadler, Marianne; Sakoda, Lori C; Sciortino, Stanley; Shen, Ling; Smethurst, David; Somkin, Carol P; Van Den Eeden, Stephen K; Walter, Lawrence; Whitmer, Rachel A; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil

2015-08-01

Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. Principal component (PC) and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed, considering only nonadjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian-European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3741 genetically identified parent-child pairs, 93% were concordant for self-reported race/ethnicity; among 2018 genetically identified full-sib pairs, 96% were concordant; the lower rate for parent-child pairs was largely due to intermarriage. The parent-child pairs revealed a trend toward increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies. Copyright © 2015 by the Genetics Society of America.

Genetic association analysis of ATP binding cassette protein family reveals a novel association of ABCB1 genetic variants with epilepsy risk, but not with drug-resistance.

PubMed

Balan, Shabeesh; Bharathan, Sumitha Prameela; Vellichiramal, Neetha Nanoth; Sathyan, Sanish; Joseph, Vijai; Radhakrishnan, Kurupath; Banerjee, Moinak

2014-01-01

Epilepsy constitutes a heterogeneous group of disorders that is characterized by recurrent unprovoked seizures due to widely different etiologies. Multidrug resistance remains a major issue in clinical epileptology, where one third of patients with epilepsy continue to have seizures. Role of efflux transporters in multidrug resistant epilepsy has been attributed to drug-resistant epilepsy although, with discrepant observation in genetic studies. These discrepancies could be attributed to variety of factors such as variable definition of the anti-epileptic drug (AED)-resistance, variable epilepsy phenotypes and ethnicities among the studies. In the present study we inquired the role of multidrug transporters ABCB1 and ABCG2 variants in determining AED-resistance and susceptibility to epilepsy in three well-characterized cohorts comprising of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) (prototype for AED-resistant epilepsy); juvenile myoclonic epilepsy (JME) (prototype for AED-responsive epilepsy); and healthy non-epileptic controls, in 738 subjects of Malayalam speaking south Indian ancestry. ABCB1 and ABCG2 variants were not found to be associated with drug resistance when AED-resistant and AED-responsive cohorts were compared. However, a significant association was observed between ABCB1 (C3435T) rs1045642 and risk of having epilepsy (MTLE-HS and JME pooled cohort; genotypic p-value = 0.0002; allelic p-value = 0.004). This association was seen persistent with MTLE-HS (genotypic p-value = 0.0008; allelic p-value = 0.004) and also with JME (genotypic p-value = 0.01; allelic p-value = 0.05) cohort individually. In-silico functional prediction indicated that ABCB1 rs1045642 has a deleterious impact on protein coding function and in splicing regulation. We conclude that the ABCB1 and ABCG2 variants do not confer to AED-resistance in the study population. However, ABCB1 rs1045642 increases vulnerability to epilepsy with greater tendency for MTLE-HS in south Indian ancestry from Kerala.

Diagnostic Yield of Chromosomal Microarray Analysis in a Cohort of Patients with Autism Spectrum Disorders from a Highly Consanguineous Population

ERIC Educational Resources Information Center

Al-Mamari, Watfa; Al-Saegh, Abeer; Al-Kindy, Adila; Bruwer, Zandre; Al-Murshedi, Fathiya; Al-Thihli, Khalid

2015-01-01

Autism Spectrum Disorders are a complicated group of disorders characterized with heterogeneous genetic etiologies. The genetic investigations for this group of disorders have expanded considerably over the past decade. In our study we designed a tired approach and studied the diagnostic yield of chromosomal microarray analysis on patients…

Characterization of the Three-Factor Eating Questionnaire scores of a young French cohort.

PubMed

Lesdéma, Aurélie; Fromentin, Gilles; Daudin, Jean-Jacques; Arlotti, Agathe; Vinoy, Sophie; Tome, Daniel; Marsset-Baglieri, Agnès

2012-10-01

The aims of our study were to characterize the psychological dimensions of eating behaviour of young French adults as measured by the Three Factor Eating Questionnaire (TFEQ) and to analyze the association between the 3 TFEQ mean scores (main scales and subscales) and gender, Body Mass Index (BMI) and socio-demographic data in this population. An online TFEQ questionnaire was used with a nationally representative sample of 1000 young French people (aged 20-39yrs). The average scores were 6.3±0.1 (sem) for dietary restraint, 6.0±0.1 for disinhibition and 5.0±0.1 for hunger. Compared to the limit commonly used in human food studies, young French adults were characterized by low restraint and low disinhibition levels. There was a significant gender effect on both restraint and disinhibition scores, with women showing significantly higher scores than men. Concerning the link between TFEQ scores and BMI, there was a significant effect of the BMI category on cognitive restraint, disinhibition and hunger. Disinhibition was the factor most strongly associated to BMI, independently of gender. Our results highlight both the importance of taking into account not only disinhibition but also cognitive restraint and the usefulness of subscales when studying eating behaviour and its link to body weight. We characterize the eating behaviour of a French cohort with criteria often chosen for healthy volunteers in human food studies. Consequently, we suggest new TFEQ limits (6 for cognitive restraint and disinhibition, 5 for hunger) lower than those traditionally used for this category of the population in clinical food studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

Do Stem Taper Microgrooves Influence Taper Corrosion in Total Hip Arthroplasty? A Matched Cohort Retrieval Study

PubMed Central

Arnholt, Christina M.; MacDonald, Daniel W.; Underwood, Richard; Guyer, Eric P.; Rimnac, Clare M.; Kurtz, Steven M.; Mont, Michael A.; Klein, Gregg; Lee, Gwo-Chin; Chen, Antonia F.; Hamlin, Brian; Cates, Harold; Malkani, Arthur; Kraay, Matthew

2017-01-01

Background Previous studies identified imprinting of the stem morphology onto the interior head bore, leading researchers to hypothesize an influence of taper topography on mechanically assisted crevice corrosion (MACC). The purpose of this study was to analyze whether micro-grooved stem tapers result in greater fretting corrosion damage than smooth stem tapers. Methods A matched cohort of 120 retrieved head-stem pairs from metal-on-polyethylene bearings was created controlling for implantation time, flexural rigidity, apparent length of engagement, and head size. There were two groups of 60 heads each, mated with either smooth or micro-grooved stem tapers. A high precision roundness machine was used to measure and categorize the surface morphology. Fretting corrosion damage at the head/neck junction was characterized using the Higgs-Goldberg scoring method. Fourteen of the most damaged heads, were analyzed for the maximum depth of material loss and focused ion beam (FIB) cross-sectioned to view oxide and base metal. Results Fretting corrosion damage was not different between the two cohorts at the femoral head (p = 0.14, Mann Whitney) or stem tapers (p = 0.35). There was no difference in the maximum depths of material loss between the cohorts (p = 0.71). Cross sectioning revealed contact damage, signs of micro-motion, and chromium rich oxide layers in both cohorts. Micro-groove imprinting did not appear to have a different effect on the fretting corrosion behavior. Conclusion The results of this matched cohort retrieval study do not support the hypothesis that taper surfaces with micro-grooved stems exhibit increased in vivo fretting corrosion damage or material release. PMID:28111124

Phenotypic heterogeneity and mutational spectrum in a cohort of 45 Italian males subjects with X-linked ectodermal dysplasia.

PubMed

Guazzarotti, L; Tadini, G; Mancini, G E; Giglio, S; Willoughby, C E; Callea, M; Sani, I; Nannini, P; Mameli, C; Tenconi, A A; Mauri, S; Bottero, A; Caimi, A; Morelli, M; Zuccotti, G V

2015-04-01

Ectodermal dysplasias (EDs) are a group of genetic disorders characterized by the abnormal development of the ectodermal-derived structures. X-linked hypohidrotic ectodermal dysplasia, resulting from mutations in ED1 gene, is the most common form. The main purpose of this study was to characterize the phenotype spectrum in 45 males harboring ED1 mutations. The study showed that in addition to the involvement of the major ectodermal tissues, the majority of patients also have alterations of several minor ectodermal-derived structures. Characterizing the clinical spectrum resulting from ED1 gene mutations improves diagnosis and can direct clinical care. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Repeated insect outbreaks promote multi-cohort aspen mixedwood forests in Northern Minnesota, USA

Treesearch

Michael Reinikainen; Anthony W. D' Amato; Shawn. Fraver

2012-01-01

Characterizing the timing, severity, and agents of historic forest disturbances is critical to developing management and conservation strategies based on natural processes. Typically such information is derived from retrospective studies of remnant old-growth forests; however, this approach has limited application in regions dominated by secondary forests heavily...

Meta-Review of the Quantity and Quality of Evidence for Knee Arthroplasty Devices.

PubMed

Gagliardi, Anna R; Ducey, Ariel; Lehoux, Pascale; Ross, Sue; Trbovich, Patricia; Easty, Anthony; Bell, Chaim; Takata, Julie; Pabinger, Christof; Urbach, David R

2016-01-01

Some cardiovascular devices are licensed based on limited evidence, potentially exposing patients to devices that are not safe or effective. Research is needed to ascertain if the same is true of other types of medical devices. Knee arthroplasty is a widely-used surgical procedure yet implant failures are not uncommon. The purpose of this study was to characterize available evidence on the safety and effectiveness of knee implants. A review of primary studies included in health technology assessments (HTA) on total (TKA) and unicompartmental knee arthroplasty (UKA) was conducted. MEDLINE, EMBASE, CINAHL, Cochrane Library and Biotechnology & BioEngineering Abstracts were searched from 2005 to 2014, plus journal tables of contents and 32 HTA web sites. Patients were aged 18 and older who underwent primary TKA or UKA assessed in cohort or randomized controlled studies. Summary statistics were used to report study characteristics. A total of 265 eligible primary studies published between 1986 and 2014 involving 59,217 patients were identified in 10 HTAs (2 low, 7 moderate, 1 high risk of bias). Most evaluated TKA (198, 74.5%). The quality of evidence in primary studies was limited. Most studies were industry-funded (23.8%) or offered no declaration of funding or conflict of interest (44.9%); based on uncontrolled single cohorts (58.5%), enrolled fewer than 100 patients (66.4%), and followed patients for 2 years or less (UKA: single cohort 29.8%, comparative cohort 16.7%, randomized trial 25.0%; TKA: single cohort 25.0%, comparative cohort 31.4%, randomized trial 48.6%). Furthermore, most devices were evaluated in only one study (55.3% TKA implants, 61.1% UKA implants). Patients, physicians, hospitals and payers rely on poor-quality evidence to support decisions about knee implants. Further research is needed to explore how decisions about the use of devices are currently made, and how the evidence base for device safety and effectiveness can be strengthened.

Risk factors for autistic regression: results of an ambispective cohort study.

PubMed

Zhang, Ying; Xu, Qiong; Liu, Jing; Li, She-chang; Xu, Xiu

2012-08-01

A subgroup of children diagnosed with autism experience developmental regression featured by a loss of previously acquired abilities. The pathogeny of autistic regression is unknown, although many risk factors likely exist. To better characterize autistic regression and investigate the association between autistic regression and potential influencing factors in Chinese autistic children, we conducted an ambispective study with a cohort of 170 autistic subjects. Analyses by multiple logistic regression showed significant correlations between autistic regression and febrile seizures (OR = 3.53, 95% CI = 1.17-10.65, P = .025), as well as with a family history of neuropsychiatric disorders (OR = 3.62, 95% CI = 1.35-9.71, P = .011). This study suggests that febrile seizures and family history of neuropsychiatric disorders are correlated with autistic regression.

Enteric Disease Surveillance Under the AFHSC-GEIS: Current Efforts, Landscape Analysis and Vision Forward

DTIC Science & Technology

2011-01-01

Severe diarrhea study at Cairo University • Case-control study of modifiable risk behaviors • Molecular biology and cholera/ rotavirus microbiology...capacity as WHO Rotavirus Reference Laboratory • Norovirus outbreak response support, Incirlik Air Base, Turkey NMRCD-Peru • Cohort study among basic...identified rotavirus as the leading causative agent • Advanced characterization of Campylobacter spp. and Shigella spp. USAMRU-K • Movement of Enteric

Serum metabolites are associated with all-cause mortality in chronic kidney disease.

PubMed

Hu, Jiun-Ruey; Coresh, Josef; Inker, Lesley A; Levey, Andrew S; Zheng, Zihe; Rebholz, Casey M; Tin, Adrienne; Appel, Lawrence J; Chen, Jingsha; Sarnak, Mark J; Grams, Morgan E

2018-06-02

Chronic kidney disease (CKD) involves significant metabolic abnormalities and has a high mortality rate. Because the levels of serum metabolites in patients with CKD might provide insight into subclinical disease states and risk for future mortality, we determined which serum metabolites reproducibly associate with mortality in CKD using a discovery and replication design. Metabolite levels were quantified via untargeted liquid chromatography and mass spectroscopy from serum samples of 299 patients with CKD in the Modification of Diet in Renal Disease (MDRD) study as a discovery cohort. Six among 622 metabolites were significantly associated with mortality over a median follow-up of 17 years after adjustment for demographic and clinical covariates, including urine protein and measured glomerular filtration rate. We then replicated associations with mortality in 963 patients with CKD from the African American Study of Kidney Disease and Hypertension (AASK) cohort over a median follow-up of ten years. Three of the six metabolites identified in the MDRD cohort replicated in the AASK cohort: fumarate, allantoin, and ribonate, belonging to energy, nucleotide, and carbohydrate pathways, respectively. Point estimates were similar in both studies and in meta-analysis (adjusted hazard ratios 1.63, 1.59, and 1.61, respectively, per doubling of the metabolite). Thus, selected serum metabolites were reproducibly associated with long-term mortality in CKD beyond markers of kidney function in two well characterized cohorts, providing targets for investigation. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Preeclampsia does not share common risk alleles in 9p21 with coronary artery disease and type 2 diabetes.

PubMed

Kaartokallio, Tea; Lokki, A Inkeri; Peterson, Hanna; Kivinen, Katja; Hiltunen, Leena; Salmela, Elina; Lappalainen, Tuuli; Maanselkä, Paula; Heino, Sanna; Knuutila, Sakari; Sayed, Ayat; Poston, Lucilla; Brennecke, Shaun P; Johnson, Matthew P; Morgan, Linda; Moses, Eric K; Kere, Juha; Laivuori, Hannele

2016-08-01

Preeclampsia is a common and partially genetic pregnancy complication characterized by hypertension and proteinuria. Association with cardiovascular disease and type 2 diabetes has been reported in 9p21 by several genome-wide association studies. It has been hypothesized that cardiometabolic diseases may share common etiology with preeclampsia. We tested association with the 9p21 region to preeclampsia in the Finnish population by genotyping 23 tagging single nucleotide polymorphisms (SNPs) in 15 extended preeclampsia families and in a nationwide cohort consisting of 281 cases and 349 matched controls. Replication was conducted in additional datasets. Four SNPs (rs7044859, rs496892, rs564398 and rs7865618) showed nominal association (p ≤ 0.024 uncorrected) with preeclampsia in the case-control cohort. To increase power, we genotyped two SNPs in additional 388 cases and 341 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort. Partial replication was also attempted in a UK cohort (237 cases and 199 controls) and in 74 preeclamptic families from Australia/New Zealand. We were unable to replicate the initial association in the extended Finnish dataset or in the two international cohorts. Our study did not find evidence for the involvement of the 9p21 region in the risk of preeclampsia. Key Message Chromosome 9p21 is not associated with preeclampsia.

Prescription Opioid Abuse, Prescription Opioid Addiction, and Heroin Abuse among Adolescents in a Recovery High School: A Pilot Study

ERIC Educational Resources Information Center

Vosburg, Suzanne K.; Eaton, Thomas A.; Sokolowska, Marta; Osgood, Eric D.; Ashworth, Judy B.; Trudeau, Jeremiah J.; Muffett-Lipinski, Michelle; Katz, Nathaniel P.

2016-01-01

The progression from prescription opioid (RXO) abuse to RXO addiction is not well understood in adolescents, nor is the progression from RXO addiction to heroin abuse. The purpose of this pilot study was to characterize the development of RXO drug abuse, RXO drug addiction, and heroin abuse in a small cohort of adolescents recovering from opioid…

Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysis.

PubMed

Wallach, Joshua D; Egilman, Alexander C; Dhruva, Sanket S; McCarthy, Margaret E; Miller, Jennifer E; Woloshin, Steven; Schwartz, Lisa M; Ross, Joseph S

2018-05-24

To characterize postmarketing requirements for new drugs and biologics approved by the US Food and Drug Administration (FDA), and to examine rates and timeliness of registration, results reporting, and publication of required prospective cohort studies, registries, and clinical trials. Cross sectional analysis. Postmarketing requirements for all new drugs and biologics approved by the FDA between 1 January 2009 and 31 December 2012, with follow-up up to 15 November 2017. Postmarketing requirements and their characteristics known at the time of FDA approval, including FDA authority, study design, and study characteristics. Rates and timeliness of registration and results reporting on ClinicalTrials.gov and publication in peer reviewed journals of required prospective cohort studies, registries, and clinical trials. Between 2009 and 12, the FDA approved 97 new drugs and biologics for 106 indications with at least one postmarketing requirement at the time of first approval, for a total of 437 postmarketing requirements. Postmarket study descriptions were short (median word count 44 (interquartile range 29-71)) and often lacked information to determine an up to date progress (131 (30%)). 220 (50.3%) postmarketing requirements were for new animal or other studies (including pharmacokinetic studies); 134 (30.7%) were for prospective cohort studies, registries, and clinical trials; and 83 (19.0%) were for secondary analyses or follow-up studies. Of 110 clinical trials, 38 (34.5%), 44 (40.0%), 62 (56.4%), 66 (60.0%), and 98 (89.1%) did not report enough information to establish use of randomization, comparator type, allocation, outcome, and number of patients to be enrolled, respectively. Of 134 required prospective cohort studies, registries, and clinical trials, 102 (76.1%) were registered on ClinicalTrials.gov; of 50 registered and completed studies, 36 (72.0%) had reported results on ClinicalTrials.gov. Among 65 completed studies, 47 (72.3%) had either reported results or were published a median of 47 months (interquartile range 32-67) after FDA approval. 32 (68.1%) of these 47 studies did not report results publicly by the time of their original FDA report submission deadline. Postmarketing requirements for new drugs and biologics were often briefly described and did not contain enough information to characterize study designs. Approximately three quarters of postmarketing requirements for prospective cohort studies, registries, and clinical trials were registered on ClinicalTrials.gov, and nearly three quarters of completed studies reported results or were published, suggesting that at least a quarter of these required studies are not being publicly disseminated. 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.

Single-dose pharmacokinetics and safety of azilsartan medoxomil in children and adolescents with hypertension as compared to healthy adults.

PubMed

Webb, Nicholas J A; Wells, Thomas; Tsai, Max; Zhao, Zhen; Juhasz, Attila; Dudkowski, Caroline

2016-04-01

This open-label, multicenter, single-dose study characterized the pharmacokinetics and short-term safety of azilsartan medoxomil (AZL-M) in hypertensive pediatric subjects (12-16 years [cohort 1a; n = 9]; 6-11 years [cohort 2; n = 8]; 4-5 years [cohort 3; n = 3]). Model-based simulations were performed to guide dosing, especially in 1-5-year olds, who were difficult to enroll. AZL-M was dosed according to body weight (20-60-mg tablet, cohorts 1a and 2; 0.66 mg/kg granule suspension, cohort 3). In cohort 1, gender-matched healthy adults (cohort 1b; n = 9) received AZL-M 80 mg. Exposure to AZL (active moiety of AZL-M), measured by dose-/body weight-normalized C max and AUC0-∞, was ∼15-30 % lower in pediatric subjects versus adults. In simulations, exposure with 0.66 mg/kg AZL-M in pediatric subjects weighing 8-25 kg approximated to AZL-M 40 mg (typical starting dose) in adults. The simulations suggest that 25-50-kg subjects require half the adult dose (10-40 mg), whereas 50-100-kg subjects can use the same dosing as adults. Adverse events were mild in intensity, apart from one moderate event (migraine). This dosing strategy should be safe in pediatric patients, as AZL exposure would not exceed that seen in adults with the highest approved AZL-M dose (80 mg).

Comprehensive molecular diagnosis of 67 Chinese Usher syndrome probands: high rate of ethnicity specific mutations in Chinese USH patients.

PubMed

Jiang, Lichun; Liang, Xiaofang; Li, Yumei; Wang, Jing; Zaneveld, Jacques Eric; Wang, Hui; Xu, Shan; Wang, Keqing; Wang, Binbin; Chen, Rui; Sui, Ruifang

2015-09-04

Usher syndrome (USH) is the most common disease causing combined deafness and blindness. It is predominantly an autosomal recessive genetic disorder with occasionally digenic cases. Molecular diagnosis of USH patients is important for disease management. Few studies have tried to find the genetic cause of USH in Chinese patients. This study was designed to determine the mutation spectrum of Chinese USH patients. We applied next generation sequencing to characterize the mutation spectrum in 67 independent Chinese families with at least one member diagnosed with USH. Blood was collected at Peking Union Medical College Hospital. This cohort is one of the largest USH cohorts reported. We utilized customized panel and whole exome sequencing, variant analysis, Sanger validation and segregation tests to find disease causing mutations in these families. We identified biallelic disease causing mutations in known USH genes in 70 % (49) of our patients. As has been previously reported, MYO7A is the most frequently mutated gene in our USH type I patients while USH2A is the most mutated gene in our USH type II patients. In addition, we identify mutations in CLRN1, DFNB31, GPR98 and PCDH15 for the first time in Chinese USH patients. Together, mutations in CLRN1, DNFB31, GPR98 and PCDH15 account for 11.4 % of disease in our cohort. Interestingly, although the spectrum of disease genes is quite similar between our Chinese patient cohort and other patient cohorts from different (and primarily Caucasian) ethnic backgrounds, the mutations themselves are dramatically different. In particular, 76 % (52/68) of alleles found in this study have never been previously reported. Interestingly, we observed a strong enrichment for severe protein truncating mutations expected to have severe functional consequence on the protein in USH II patients compared to the reported mutation spectrum in RP patients, who often carry partial protein truncating mutations. Our study provides the first comprehensive genetic characterization of a large collection of Chinese USH patients. Up to 90 % of USH patients have disease caused by mutations in known USH disease genes. By combining NGS-based molecular diagnosis and patient clinical information, a more accurate diagnosis, prognosis and personalized treatment of USH patients can be achieved.

Patterns and Correlates of Substance Use among Affluent, Suburban High School Students

ERIC Educational Resources Information Center

McMahon, Thomas J.; Luthar, Suniya S.

2006-01-01

Despite ongoing concern about substance use during adolescence, very little is known about alcohol and drug use among teens living in affluent social settings. In this longitudinal study, cluster analysis was used to characterize patterns of substance use and change in other dimensions of psychosocial adjustment within a cohort of 292 high school…

Dyspnea in Chronic Fatigue Syndrome (CFS): Comparison of Two Prospective Cross-Sectional Studies

PubMed Central

Ravindran, Murugan K.; Adewuyi, Oluwatoyin; Zheng, Yin; Rayhan, Rakib U.; Le, Uyenphuong; Timbol, Christian R.; Merck, Samantha; Esteitie, Rania; Cooney, Michelle; Read, Charles; Baraniuk, James N.

2013-01-01

Chronic Fatigue Syndrome (CFS) subjects have many systemic complaints including shortness of breath. Dyspnea was compared in two CFS and control cohorts to characterize pathophysiology. Cohort 1 of 257 CFS and 456 control subjects were compared using the Medical Research Council chronic Dyspnea Scale (MRC Score; range 0-5). Cohort 2 of 106 CFS and 90 controls answered a Dyspnea Severity Score (range 0-20) adapted from the MRC Score. Subsets of both cohorts completed CFS Severity Scores, fatigue, and other questionnaires. A subset had pulmonary function and total lung capacity measurements. Results show MRC Scores were equivalent between sexes in Cohort 1 CFS (1.92 [1.72-2.16]; mean [95% C.I.]) and controls (0.31 [0.23-0.39]; p<0.0001). Receiver-operator curves identified 2 as the threshold for positive MRC Scores in Cohort 1. This indicated 54% of CFS, but only 3% of controls, had significant dyspnea. In Cohort 2, Dyspnea Score threshold of 4 indicated shortness of breath in 67% of CFS and 23% of controls. Cohort 2 Dyspnea Scores were higher for CFS (7.80 [6.60-9.00]) than controls (2.40 [1.60-3.20]; p<0.0001). CFS had significantly worse fatigue and other complaints compared to controls. Pulmonary function was normal in CFS, but Borg scores and sensations of chest pain and dizziness were significantly greater during testing than controls. General linear model of Cohort 2 CFS responses linked Dyspnea with rapid heart rate, chest pain and dizziness. In conclusion, sensory hypersensitivity without airflow limitation contributed to dyspnea in CFS. Correlates of dyspnea in controls were distinct from CFS suggesting different mechanisms. PMID:23445698

Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies.

PubMed

Ravindran, Murugan; Adewuyi, Oluwatoyin; Zheng, Yin; Rayhan, Rakib U; Le, Uyenphuong; Timbol, Christian; Merck, Samantha; Esteitie, Rania; Read, Charles; Cooney, Michelle; Baraniuk, James

2012-12-12

Chronic Fatigue Syndrome (CFS) subjects have many systemic complaints including shortness of breath. Dyspnea was compared in two CFS and control cohorts to characterize pathophysiology. Cohort 1 of 257 CFS and 456 control subjects were compared using the Medical Research Council chronic Dyspnea Scale (MRC Score; range 0-5). Cohort 2 of 106 CFS and 90 controls answered a Dyspnea Severity Score (range 0-20) adapted from the MRC Score. Subsets of both cohorts completed CFS Severity Scores, fatigue, and other questionnaires. A subset had pulmonary function and total lung capacity measurements. Results show MRC Scores were equivalent between sexes in Cohort 1 CFS (1.92 [1.72-2.16]; mean [95% C.I.]) and controls (0.31 [0.23-0.39]; p<0.0001). Receiver-operator curves identified 2 as the threshold for positive MRC Scores in Cohort 1. This indicated 54% of CFS, but only 3% of controls, had significant dyspnea. In Cohort 2, Dyspnea Score threshold of 4 indicated shortness of breath in 67% of CFS and 23% of controls. Cohort 2 Dyspnea Scores were higher for CFS (7.80 [6.60-9.00]) than controls (2.40 [1.60-3.20]; p<0.0001). CFS had significantly worse fatigue and other complaints compared to controls. Pulmonary function was normal in CFS, but Borg scores and sensations of chest pain and dizziness were significantly greater during testing than controls. General linear model of Cohort 2 CFS responses linked Dyspnea with rapid heart rate, chest pain and dizziness. In conclusion, sensory hypersensitivity without airflow limitation contributed to dyspnea in CFS. Correlates of dyspnea in controls were distinct from CFS suggesting different mechanisms.

The Minnesota Adolescent Community Cohort Study: Design and Baseline Results

PubMed Central

Forster, Jean; Chen, Vincent; Perry, Cheryl; Oswald, John; Willmorth, Michael

2014-01-01

The Minnesota Adolescent Community Cohort (MACC) Study is a population-based, longitudinal study that enrolled 3636 youth from Minnesota and 605 youth from comparison states age 12 to 16 years in 2000–2001. Participants have been surveyed by telephone semi-annually about their tobacco-related attitudes and behaviors. The goals of the study are to evaluate the effects of the Minnesota Youth Tobacco Prevention Initiative and its shutdown on youth smoking patterns, and to better define the patterns of development of tobacco use in adolescents. A multilevel sample was constructed representing individuals, local jurisdictions and the entire state, and data are collected to characterize each of these levels. This paper presents the details of the multilevel study design. We also provide baseline information about MACC participants including demographics and tobacco-related attitudes and behaviors. This paper describes smoking prevalence at the local level, and compares MACC participants to the state as a whole. PMID:21360063

Gene-Lifestyle Interactions in Complex Diseases: Design and Description of the GLACIER and VIKING Studies

PubMed Central

Kurbasic, Azra; Poveda, Alaitz; Chen, Yan; Ågren, Åsa; Engberg, Elisabeth; Hu, Frank B.; Johansson, Ingegerd; Barroso, Ines; Brändström, Anders; Hallmans, Göran; Renström, Frida; Franks, Paul W.

2014-01-01

Most complex diseases have well-established genetic and non-genetic risk factors. In some instances, these risk factors are likely to interact, whereby their joint effects convey a level of risk that is either significantly more or less than the sum of these risks. Characterizing these gene-environment interactions may help elucidate the biology of complex diseases, as well as to guide strategies for their targeted prevention. In most cases, the detection of gene-environment interactions will require sample sizes in excess of those needed to detect the marginal effects of the genetic and environmental risk factors. Although many consortia have been formed, comprising multiple diverse cohorts to detect gene-environment interactions, few robust examples of such interactions have been discovered. This may be because combining data across studies, usually through meta-analysis of summary data from the contributing cohorts, is often a statistically inefficient approach for the detection of gene-environment interactions. Ideally, single, very large and well-genotyped prospective cohorts, with validated measures of environmental risk factor and disease outcomes should be used to study interactions. The presence of strong founder effects within those cohorts might further strengthen the capacity to detect novel genetic effects and gene-environment interactions. Access to accurate genealogical data would also aid in studying the diploid nature of the human genome, such as genomic imprinting (parent-of-origin effects). Here we describe two studies from northern Sweden (the GLACIER and VIKING studies) that fulfill these characteristics. PMID:25396097

Gene-Lifestyle Interactions in Complex Diseases: Design and Description of the GLACIER and VIKING Studies.

PubMed

Kurbasic, Azra; Poveda, Alaitz; Chen, Yan; Agren, Asa; Engberg, Elisabeth; Hu, Frank B; Johansson, Ingegerd; Barroso, Ines; Brändström, Anders; Hallmans, Göran; Renström, Frida; Franks, Paul W

2014-12-01

Most complex diseases have well-established genetic and non-genetic risk factors. In some instances, these risk factors are likely to interact, whereby their joint effects convey a level of risk that is either significantly more or less than the sum of these risks. Characterizing these gene-environment interactions may help elucidate the biology of complex diseases, as well as to guide strategies for their targeted prevention. In most cases, the detection of gene-environment interactions will require sample sizes in excess of those needed to detect the marginal effects of the genetic and environmental risk factors. Although many consortia have been formed, comprising multiple diverse cohorts to detect gene-environment interactions, few robust examples of such interactions have been discovered. This may be because combining data across studies, usually through meta-analysis of summary data from the contributing cohorts, is often a statistically inefficient approach for the detection of gene-environment interactions. Ideally, single, very large and well-genotyped prospective cohorts, with validated measures of environmental risk factor and disease outcomes should be used to study interactions. The presence of strong founder effects within those cohorts might further strengthen the capacity to detect novel genetic effects and gene-environment interactions. Access to accurate genealogical data would also aid in studying the diploid nature of the human genome, such as genomic imprinting (parent-of-origin effects). Here we describe two studies from northern Sweden (the GLACIER and VIKING studies) that fulfill these characteristics.

New cohort growth and survival in variable retention harvests of a pine ecosystem in Minnesota, USA

Treesearch

Rebecca A. Montgomery; Brian J. Palik; Suzanne B. Boyden; Peter B. Reich

2013-01-01

There is significant interest in silvicultural systems such as variable retention harvesting (VRH) that emulate natural disturbance and increase structural complexity, spatial heterogeneity, and biological diversity in managed forests. However, the consequences of variable retention harvesting for new cohort growth and survival are not well characterized in many forest...

Host Control of Fungal Infections: Lessons from Basic Studies and Human Cohorts.

PubMed

Lionakis, Michail S; Levitz, Stuart M

2018-04-26

In the last few decades, the AIDS pandemic and the significant advances in the medical management of individuals with neoplastic and inflammatory conditions have resulted in a dramatic increase in the population of immunosuppressed patients with opportunistic, life-threatening fungal infections. The parallel development of clinically relevant mouse models of fungal disease and the discovery and characterization of several inborn errors of immune-related genes that underlie inherited human susceptibility to opportunistic mycoses have significantly expanded our understanding of the innate and adaptive immune mechanisms that protect against ubiquitous fungal exposures. This review synthesizes immunological knowledge derived from basic mouse studies and from human cohorts and provides an overview of mammalian antifungal host defenses that show promise for informing therapeutic and vaccination strategies for vulnerable patients.

Pearson Syndrome: A Retrospective Cohort Study from the Marrow Failure Study Group of A.I.E.O.P. (Associazione Italiana Emato-Oncologia Pediatrica).

PubMed

Farruggia, Piero; Di Cataldo, Andrea; Pinto, Rita M; Palmisani, Elena; Macaluso, Alessandra; Valvo, Laura Lo; Cantarini, Maria E; Tornesello, Assunta; Corti, Paola; Fioredda, Francesca; Varotto, Stefania; Martire, Baldo; Moroni, Isabella; Puccio, Giuseppe; Russo, Giovanna; Dufour, Carlo; Pillon, Marta

2016-01-01

Pearson syndrome (PS) is a very rare and often fatal multisystemic mitochondrial disorder involving the liver, kidney, pancreas, and hematopoietic and central nervous system. It is characterized principally by a transfusion-dependent anemia that usually improves over time, a tendency to develop severe infections, and a high mortality rate. We describe a group of 11 PS patients diagnosed in Italy in the period 1993-2014. The analysis of this reasonably sized cohort of patients contributes to the clinical profile of the disease and highlights a rough incidence of 1 case/million newborns. Furthermore, it seems that some biochemical parameters like increased serum alanine and urinary fumaric acid can help to address an early diagnosis.

[Laservaporization of the prostate: current status of the greenlight and diode laser].

PubMed

Rieken, M; Bachmann, A; Gratzke, C

2013-03-01

In the last decade laser vaporization of the prostate has emerged as a safe and effective alternative to transurethral resection of the prostate (TURP). This was facilitated in particular by the introduction of photoselective vaporization of the prostate (PVP) with a 532 nm 80 W KTP laser in 2002. Prospective randomized trials comparing PVP and TURP with a maximum follow-up of 3 years mostly demonstrated comparable functional results. Cohort studies showed a safe application of PVP in patients under oral anticoagulation and with large prostates. Systems from various manufacturers with different maximum power output and wavelengths are now available for diode laser vaporization of the prostate. Prospective randomized trials comparing diode lasers and TURP are not yet available. In cohort studies and comparative studies PVP diode lasers are characterized by excellent hemostatic properties but functional results vary greatly with some studies reporting high reoperation rates.

Paradoxical dissociation between hepatic fat content and de novo lipogenesis due to PNPLA3 sequence variant.

PubMed

Mancina, Rosellina M; Matikainen, Niina; Maglio, Cristina; Söderlund, Sanni; Lundbom, Nina; Hakkarainen, Antti; Rametta, Raffaela; Mozzi, Enrico; Fargion, Silvia; Valenti, Luca; Romeo, Stefano; Taskinen, Marja-Riitta; Borén, Jan

2015-05-01

Nonalcoholic fatty liver disease (NAFLD) is an emerging epidemic disease characterized by increased hepatic fat, due to an imbalance between synthesis and removal of hepatic lipids. In particular, increased hepatic de novo lipogenesis (DNL) is a key feature associated with NAFLD. The genetic variations I148M in PNPLA3 and E167K in TM6SF2 confer susceptibility to NAFLD. Here we aimed to investigate the contribution of DNL to liver fat accumulation in the PNPLA3 I148M or TM6SF2 E167K genetic determinants of NAFLD. The PNPLA3 I148M and TM6SF2 E167K were genotyped in two well-characterized cohorts of Europeans. In the first cohort (Helsinki cohort; n = 88), we directly quantified hepatic DNL using deuterated water. In the second cohort (Milan cohort; n = 63), we quantified the hepatic expression of SREBP1c that we have found previously associated with increased fat content. Liver fat was measured by magnetic resonance proton spectroscopy in the Helsinki cohort, and by histological assessment of liver biopsies in the Milan cohort. PNPLA3 148M was associated with lower DNL and expression of the lipogenic transcription factor SREBP1c despite substantial increased hepatic fat content. Our data show a paradoxical dissociation between hepatic DNL and hepatic fat content due to the PNPLA3 148M allele indicating that increased DNL is not a key feature in all individuals with hepatic steatosis, and reinforces the contribution of decreased mobilization of hepatic triglycerides for hepatic lipid accumulation in subject with the PNPLA3 148M allele.

Cohort Profile: Recruitment cohorts in the neuropsychological substudy of the Multicenter AIDS Cohort Study.

PubMed

Becker, James T; Kingsley, Lawrence A; Molsberry, Samantha; Reynolds, Sandra; Aronow, Aaron; Levine, Andrew J; Martin, Eileen; Miller, Eric N; Munro, Cynthia A; Ragin, Ann; Sacktor, Ned; Selnes, Ola A

2015-10-01

The Multicenter AIDS Cohort Study (MACS) is one of the largest and longest running studies of the natural and treated history of HIV disease. The Neuropsychological (NP) substudy was begun in 1988 following reports of significant adverse neurological consequences of HIV disease, including dementia. The goal was to characterize the neuropsychological deficits among individuals with HIV disease, and track the natural history of the neurological complications over time. There were three distinct MACS recruitment stages that focused on different groups of HIV-infected men, or men at risk for infection. Initially, a subcohort was evaluated semi-annually with NP tests but, beginning in 2005, the entire group of MACS participants have had NP examinations biannually, unless closer follow-up was warranted. The participants complete a battery of NP tests, and are classified as either normal, mildly or severely impaired using the Antinori criteria for HIV-Associated Neurocognitive Disorder (HAND). Additional behavioural data, including mood state and psychoactive substance use, are recorded as part of the main MACS data collection. The MACS public data set (PDS) has been available since 1994 and includes baseline and 6-monthly follow-up data. Beginning in October 1995, the PDS has been released annually with new releases superseding previous versions. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

The Structure of Memory in Infants and Toddlers: An SEM Study with Full-Terms and Preterms

ERIC Educational Resources Information Center

Rose, Susan A.; Feldman, Judith F.; Jankowski, Jeffery J.; Van Rossem, Ronan

2011-01-01

There is considerable dispute about the nature of infant memory. Using SEM models, we examined whether popular characterizations of the structure of adult memory, including the two-process theory of recognition, are applicable in the infant and toddler years. The participants were a cohort of preterms and full-terms assessed longitudinally--at 1,…

Copy number analysis of NIPBL in a cohort of 510 patients reveals rare copy number variants and a mosaic deletion.

PubMed

Cheng, Yu-Wei; Tan, Christopher A; Minor, Agata; Arndt, Kelly; Wysinger, Latrice; Grange, Dorothy K; Kozel, Beth A; Robin, Nathaniel H; Waggoner, Darrel; Fitzpatrick, Carrie; Das, Soma; Del Gaudio, Daniela

2014-03-01

Cornelia de Lange syndrome (CdLS) is a genetically heterogeneous disorder characterized by growth retardation, intellectual disability, upper limb abnormalities, hirsutism, and characteristic facial features. In this study we explored the occurrence of intragenic NIPBL copy number variations (CNVs) in a cohort of 510 NIPBL sequence-negative patients with suspected CdLS. Copy number analysis was performed by custom exon-targeted oligonucleotide array-comparative genomic hybridization and/or MLPA. Whole-genome SNP array was used to further characterize rearrangements extending beyond the NIPBL gene. We identified NIPBL CNVs in 13 patients (2.5%) including one intragenic duplication and a deletion in mosaic state. Breakpoint sequences in two patients provided further evidence of a microhomology-mediated replicative mechanism as a potential predominant contributor to CNVs in NIPBL. Patients for whom clinical information was available share classical CdLS features including craniofacial and limb defects. Our experience in studying the frequency of NIBPL CNVs in the largest series of patients to date widens the mutational spectrum of NIPBL and emphasizes the clinical utility of performing NIPBL deletion/duplication analysis in patients with CdLS.

Genetic Association Analysis of ATP Binding Cassette Protein Family Reveals a Novel Association of ABCB1 Genetic Variants with Epilepsy Risk, but Not with Drug-Resistance

PubMed Central

Balan, Shabeesh; Bharathan, Sumitha Prameela; Vellichiramal, Neetha Nanoth; Sathyan, Sanish; Joseph, Vijai; Radhakrishnan, Kurupath; Banerjee, Moinak

2014-01-01

Epilepsy constitutes a heterogeneous group of disorders that is characterized by recurrent unprovoked seizures due to widely different etiologies. Multidrug resistance remains a major issue in clinical epileptology, where one third of patients with epilepsy continue to have seizures. Role of efflux transporters in multidrug resistant epilepsy has been attributed to drug-resistant epilepsy although, with discrepant observation in genetic studies. These discrepancies could be attributed to variety of factors such as variable definition of the anti-epileptic drug (AED)-resistance, variable epilepsy phenotypes and ethnicities among the studies. In the present study we inquired the role of multidrug transporters ABCB1 and ABCG2 variants in determining AED-resistance and susceptibility to epilepsy in three well-characterized cohorts comprising of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) (prototype for AED-resistant epilepsy); juvenile myoclonic epilepsy (JME) (prototype for AED-responsive epilepsy); and healthy non-epileptic controls, in 738 subjects of Malayalam speaking south Indian ancestry. ABCB1 and ABCG2 variants were not found to be associated with drug resistance when AED-resistant and AED-responsive cohorts were compared. However, a significant association was observed between ABCB1 (C3435T) rs1045642 and risk of having epilepsy (MTLE-HS and JME pooled cohort; genotypic p-value = 0.0002; allelic p-value = 0.004). This association was seen persistent with MTLE-HS (genotypic p-value = 0.0008; allelic p-value = 0.004) and also with JME (genotypic p-value = 0.01; allelic p-value = 0.05) cohort individually. In-silico functional prediction indicated that ABCB1 rs1045642 has a deleterious impact on protein coding function and in splicing regulation. We conclude that the ABCB1 and ABCG2 variants do not confer to AED-resistance in the study population. However, ABCB1 rs1045642 increases vulnerability to epilepsy with greater tendency for MTLE-HS in south Indian ancestry from Kerala. PMID:24586633

Respiratory manifestations in 38 patients with Alström syndrome.

PubMed

Boerwinkle, Caroline; Marshall, Jan D; Bryant, Joy; Gahl, William A; Olivier, Kenneth N; Gunay-Aygun, Meral

2017-04-01

Alström syndrome (AS) is a rare, multi-system condition characterized by retinal degeneration, sensorineural hearing loss, obesity, insulin-resistant diabetes, hypertriglyceridemia, cardiomyopathy, hepatorenal disease, and recurrent respiratory infections. It belongs to a group of genetic disorders known as primary ciliopathies, which includes autosomal dominant and recessive polycystic kidney diseases, as well as Joubert and Bardet-Biedl syndromes. Prior studies have suggested phenotypic overlap between primary ciliopathies affecting the non-motile, sensory cilia, and primary ciliary dyskinesia (PCD), a motile ciliopathy characterized by respiratory tract disease. We describe the burden of oto-sino-pulmonary disease in 38 individuals with AS and examines the degree of clinical overlap between PCD and AS. Evaluation at the NIH Clinical Center included clinical examination, chest imaging, and clinical history surveys, as well as measurement of nasal nitric oxide (nNO) in nine patients. Recurrent otitis media was ubiquitous in the AS cohort (92%) with 50% requiring pressure equalization tube placement. A history of bronchitis/pneumonia and sinusitis was reported in 61% and 50% of individuals, respectively. PCD-characterizing symptoms (laterality defects, unexplained neonatal respiratory distress, year-round nasal congestion, and wet cough) were far less prevalent in the AS cohort compared to PCD, and the average nNO production in the AS cohort was 232 ± 57.1 nl/min compared to a cut-off of <77 nl/min for PCD. These data suggest that the oto-sino-respiratory complications in AS are prominent enough to warrant increased clinical attention, but significantly impaired respiratory cilia function as seen in PCD is unlikely in AS. (www.clinicaltrials.gov, trial NCT00068224) Pediatr Pulmonol. 2017;52:487-493. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients.

PubMed

Barbosa, M; Lopes, A; Mota, C; Martins, E; Oliveira, J; Alves, S; De Bonis, P; Mota, M do Céu; Dias, C; Rodrigues-Santos, P; Fortuna, A M; Quelhas, D; Lacerda, L; Bisceglia, L; Cardoso, M L

2012-01-01

Cystinuria is a rare autosomal inherited disorder characterized by impaired transport of cystine and dibasic aminoacids in the proximal renal tubule. Classically, cystinuria is classified as type I (silent heterozygotes) and non-type I (heterozygotes with urinary hyperexcretion of cystine). Molecularly, cystinuria is classified as type A (mutations on SLC3A1 gene) and type B (mutations on SLC7A9 gene). The goal of this study is to provide a comprehensive clinical, biochemical and molecular characterization of a cohort of 12 Portuguese patients affected with cystinuria in order to provide insight into genotype-phenotype correlations. We describe seven type I and five non-type I patients. Regarding the molecular classification, seven patients were type A and five were type B. In SLC3A1 gene, two large genomic rearrangements and 13 sequence variants, including four new variants c.611-2A>C; c.1136+44G>A; c.1597T (p.Y533N); c.*70A>G, were found. One large genomic rearrangement was found in SLC7A9 gene as well as 24 sequence variants including 3 novel variants: c.216C>T (p.C72C), c.1119G>A (p.S373S) and c.*82C>T. In our cohort the most frequent pathogenic mutations were: large rearrangements (33.3% of mutant alleles) and a missense mutation c.1400T>C (p.M467T) (11.1%). This report expands the spectrum of SLC3A1 and SLC7A9 mutations and provides guidance in the clinical implementation of molecular assays in routine genetic counseling of Portuguese patients affected with cystinuria. © 2011 John Wiley & Sons A/S.

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

PubMed

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

2014-06-01

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

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

PubMed

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

2013-01-01

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

A hybrid Bayesian hierarchical model combining cohort and case-control studies for meta-analysis of diagnostic tests: Accounting for partial verification bias.

PubMed

Ma, Xiaoye; Chen, Yong; Cole, Stephen R; Chu, Haitao

2016-12-01

To account for between-study heterogeneity in meta-analysis of diagnostic accuracy studies, bivariate random effects models have been recommended to jointly model the sensitivities and specificities. As study design and population vary, the definition of disease status or severity could differ across studies. Consequently, sensitivity and specificity may be correlated with disease prevalence. To account for this dependence, a trivariate random effects model had been proposed. However, the proposed approach can only include cohort studies with information estimating study-specific disease prevalence. In addition, some diagnostic accuracy studies only select a subset of samples to be verified by the reference test. It is known that ignoring unverified subjects may lead to partial verification bias in the estimation of prevalence, sensitivities, and specificities in a single study. However, the impact of this bias on a meta-analysis has not been investigated. In this paper, we propose a novel hybrid Bayesian hierarchical model combining cohort and case-control studies and correcting partial verification bias at the same time. We investigate the performance of the proposed methods through a set of simulation studies. Two case studies on assessing the diagnostic accuracy of gadolinium-enhanced magnetic resonance imaging in detecting lymph node metastases and of adrenal fluorine-18 fluorodeoxyglucose positron emission tomography in characterizing adrenal masses are presented. © The Author(s) 2014.

A Hybrid Bayesian Hierarchical Model Combining Cohort and Case-control Studies for Meta-analysis of Diagnostic Tests: Accounting for Partial Verification Bias

PubMed Central

Ma, Xiaoye; Chen, Yong; Cole, Stephen R.; Chu, Haitao

2014-01-01

To account for between-study heterogeneity in meta-analysis of diagnostic accuracy studies, bivariate random effects models have been recommended to jointly model the sensitivities and specificities. As study design and population vary, the definition of disease status or severity could differ across studies. Consequently, sensitivity and specificity may be correlated with disease prevalence. To account for this dependence, a trivariate random effects model had been proposed. However, the proposed approach can only include cohort studies with information estimating study-specific disease prevalence. In addition, some diagnostic accuracy studies only select a subset of samples to be verified by the reference test. It is known that ignoring unverified subjects may lead to partial verification bias in the estimation of prevalence, sensitivities and specificities in a single study. However, the impact of this bias on a meta-analysis has not been investigated. In this paper, we propose a novel hybrid Bayesian hierarchical model combining cohort and case-control studies and correcting partial verification bias at the same time. We investigate the performance of the proposed methods through a set of simulation studies. Two case studies on assessing the diagnostic accuracy of gadolinium-enhanced magnetic resonance imaging in detecting lymph node metastases and of adrenal fluorine-18 fluorodeoxyglucose positron emission tomography in characterizing adrenal masses are presented. PMID:24862512

Latent class analysis reveals clinically relevant atopy phenotypes in 2 birth cohorts.

PubMed

Hose, Alexander J; Depner, Martin; Illi, Sabina; Lau, Susanne; Keil, Thomas; Wahn, Ulrich; Fuchs, Oliver; Pfefferle, Petra Ina; Schmaußer-Hechfellner, Elisabeth; Genuneit, Jon; Lauener, Roger; Karvonen, Anne M; Roduit, Caroline; Dalphin, Jean-Charles; Riedler, Josef; Pekkanen, Juha; von Mutius, Erika; Ege, Markus J

2017-06-01

Phenotypes of childhood-onset asthma are characterized by distinct trajectories and functional features. For atopy, definition of phenotypes during childhood is less clear. We sought to define phenotypes of atopic sensitization over the first 6 years of life using a latent class analysis (LCA) integrating 3 dimensions of atopy: allergen specificity, time course, and levels of specific IgE (sIgE). Phenotypes were defined by means of LCA in 680 children of the Multizentrische Allergiestudie (MAS) and 766 children of the Protection against allergy: Study in Rural Environments (PASTURE) birth cohorts and compared with classical nondisjunctive definitions of seasonal, perennial, and food sensitization with respect to atopic diseases and lung function. Cytokine levels were measured in the PASTURE cohort. The LCA classified predominantly by type and multiplicity of sensitization (food vs inhalant), allergen combinations, and sIgE levels. Latent classes were related to atopic disease manifestations with higher sensitivity and specificity than the classical definitions. LCA detected consistently in both cohorts a distinct group of children with severe atopy characterized by high seasonal sIgE levels and a strong propensity for asthma; hay fever; eczema; and impaired lung function, also in children without an established asthma diagnosis. Severe atopy was associated with an increased IL-5/IFN-γ ratio. A path analysis among sensitized children revealed that among all features of severe atopy, only excessive sIgE production early in life affected asthma risk. LCA revealed a set of benign, symptomatic, and severe atopy phenotypes. The severe phenotype emerged as a latent condition with signs of a dysbalanced immune response. It determined high asthma risk through excessive sIgE production and directly affected impaired lung function. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Characterizing longitudinal health state transitions among heroin, cocaine, and methamphetamine users

PubMed Central

Nosyk, B; Li, L; Evans, E; Huang, D; Min, J; Kerr, T; Brecht, ML; Hser, YI

2014-01-01

Aims Characterize longitudinal patterns of drug use careers and identify determinants of drug use frequency across cohorts of primary heroin, methamphetamine (MA) and cocaine users. Design Pooled analysis of prospective cohort studies. Settings Illicit drug users recruited from community, criminal justice and drug treatment settings in California, USA. Participants We used longitudinal data on from five observational cohort studies featuring primary users of heroin (N=629), cocaine (N=694) and methamphetamine (N=474). The mean duration of follow-up was 20.9 years. Measurements Monthly longitudinal data was arranged according to five health states (incarceration, drug treatment, abstinence, non-daily and daily use). We fitted proportional hazards (PH) frailty models to determine independent differences in successive episode durations. We then executed multi-state Markov (MSM) models to estimate probabilities of transitioning between health states, and the determinants of these transitions. Findings Across primary drug use types, PH frailty models demonstrated durations of daily use diminished in successive episodes over time. MSM models revealed primary stimulant users had more erratic longitudinal patterns of drug use, transitioning more rapidly between periods of treatment, abstinence, non-daily and daily use. MA users exhibited relatively longer durations of high-frequency use. Criminal engagement had a destabilizing effect on health state durations across drug types. Longer incarceration histories were associated with delayed transitions towards cessation. Conclusions PH frailty and MSM modeling techniques provided complementary information on longitudinal patterns of drug abuse. This information can inform clinical practice and policy, and otherwise be used in health economic simulation models, designed to inform resource allocation decisions. PMID:24837584

Disease characterization of systemic lupus erythematosus (SLE) patients in Quebec.

PubMed

Ng, R; Bernatsky, S; Rahme, E

2017-08-01

Objective Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by an array of organ manifestations that can appear during flares and disappear during remissions. The objectives of this study were: (i) to examine SLE manifestation groups longitudinally in an SLE cohort; and (ii) to assess the association between early antimalarial treatment and renal manifestations. Methods Seven SLE manifestation groups-cutaneous, hematologic, lung, musculoskeletal, neuropsychiatric, serositis, renal-were tracked using Kaplan-Meier survival curves in an incident SLE cohort from Quebec health administrative data ( n = 2010). A subgroup with provincial drug insurance coverage was followed over time to examine the association between early antimalarial treatment (within three months after SLE diagnosis) and renal manifestations using a Cox proportional hazards survival model. Results Cutaneous manifestations was the most common manifestation at SLE diagnosis (30.0%, 95% CI: 27.7-32.2%). About two-thirds (66.2%, 95% CI: 63.4-68.9%) of patients had evidence of at least one SLE manifestation at diagnosis, which increased to 87.2% (95% CI: 84.2-90.3%) by the end of follow-up. After adjusting for age, sex, early concomitant systemic steroid therapy, Charlson comorbidity index, primary care visits in the year prior and other SLE manifestations at baseline, no statistically significant association was established between antimalarial therapy and renal manifestations. Conclusion This study provides insight regarding organ manifestations within a population-based sample. Most patients identified with SLE had other diagnostic evidence that supports an underlying diagnosis of SLE. No protective effects for antimalarial agents against renal manifestations could be established in this population-based cohort.

Study of the prevalence of familial autoimmune myasthenia gravis in a Spanish cohort.

PubMed

Salvado, Maria; Canela, Merce; Ponseti, Jose Maria; Lorenzo, Laura; Garcia, Cecilia; Cazorla, Sonia; Gili, Gisela; Raguer, Nuria; Gamez, Josep

2016-01-15

Myasthenia gravis (MG) is an autoimmune disease caused by a failure of neuromuscular transmission. Familial clustering has been reported despiteMG usually manifesting as a sporadic condition presumed not to be inherited. Our study investigated the prevalence of FAMG in a Spanish cohort, characterizing their phenotype,antibody titres and thymus findings. We investigated the presence of familial cases in 462 MG patients, characterizing by age and MGFA class at debut, quantitative MG score, antibody titres, MGFA post-intervention status and thymus pathology. Sixteen cases from8 unrelated pedigrees were identified. The prevalence of FAMG caseswas 3.46%.Mean age at onset was 57.8 ± 17.4 years (range=23–82). Distribution at debut was: 6 ocular, 4 IIa, 4IIb, 1 IIIa and 1 IIIb. Thymoma was identified in two of the 7 thymectomized individuals. The prevalence of FAMG in Spain is similar to other populations. Post-intervention status did not differ from sporadic autoimmune MG. As in other neuromuscular disorders, phenotype and inheritance heterogeneity are present in FAMG. In addition to the interfamilial heterogeneity observed, members of the same family affected with FAMG may even present different ages of onset, severity and thymus involvement. Further studies are necessary to clarify the role of genetic risk factors in this form of autoimmune MG.

Seizures in juvenile Huntington's disease: frequency and characterization in a multicenter cohort.

PubMed

Cloud, Leslie J; Rosenblatt, Adam; Margolis, Russel L; Ross, Christopher A; Pillai, Jagan A; Corey-Bloom, Jody; Tully, Hannah M; Bird, Thomas; Panegyres, Peter K; Nichter, Charles A; Higgins, Donald S; Helmers, Sandra L; Factor, Stewart A; Jones, Randi; Testa, Claudia M

2012-12-01

Little is known about the epilepsy that often occurs in the juvenile form of Huntington's disease (HD), but is absent from the adult-onset form. The primary aim of this study was to characterize the seizures in juvenile HD (JHD) subjects with regard to frequency, semiology, defining EEG characteristics, and response to antiepileptic agents. A multicenter, retrospective cohort was identified by database query and/or chart review. Data on age of HD onset, primary HD manifestations, number of CAG repeats, the presence or absence of seizures, seizure type(s), antiepileptic drugs used, subjects' response to antiepileptic drugs (AEDs), and EEG results were assembled, where available. Ninety subjects with genetically confirmed JHD were included. Seizures were present in 38% of subjects and were more likely to occur with younger ages of HD onset. Generalized tonic-clonic seizures were the most common seizure type, followed by tonic, myoclonic, and staring spells. Multiple seizure types commonly occurred within the same individual. Data on EEG findings and AED usage are presented. Seizure risk in JHD increases with younger age of HD onset. Our ability to draw firm conclusions about defining EEG characteristics and response to AEDs was limited by the retrospective nature of the study. Future prospective studies are required. Copyright © 2012 Movement Disorder Society.

Menstruation and the Menopause Transition

PubMed Central

Harlow, Siobán D.; Paramsothy, Pangaja

2011-01-01

SYNOPSIS This paper characterizes changes in menstrual bleeding during perimenopause, including bleeding changes that represent markers of the menopausal transition. Recent results from the Study of Women’s Health Across the Nation (SWAN), a multiethnic cohort study of midlife women, as well as data from other cohort studies of women in the midlife are reviewed. Emerging data describing subpopulation differences in the transition experience is highlighted . Early transition, defined as a persistent difference in consecutive menstrual cycle length of seven or more days, begins on average 6-8 years before the FMP. Late transition, defined by an episode of 60 or more days of amenorrhea, begins on average two years before the FMP. When treating women in the midlife, clinicians should pay careful attention to medical factors, including both conditions and treatments, that may increase menstrual blood loss or alter menstrual cycle characteristics sufficiently to obscure the onset of the menopausal transition or the FMP. PMID:21961722

Characteristics and health care resource use of subjects with COPD in the year before initiating LAMA monotherapy or LAMA+LABA combination therapy: A U.S. database study.

PubMed

Nagar, Saurabh; Patel, Jeetvan; Stanford, Richard H

2018-05-01

To characterize subjects with chronic obstructive pulmonary disease (COPD) newly initiated on long-acting muscarinic antagonists (LAMA) or dual LAMA/long-acting β2-adrenergic agonist (LABA) therapy. This pilot/preliminary analysis was a retrospective crosssectional study of subjects with COPD from the Optum Impact National Managed Care Benchmark Database. Subjects with at least one LAMA prescription in the index period (July 2008-June 2009) were included and stratified by treatment. Data were collected in the year before the index date and included comorbidities, medication use, COPD-related costs, health care resource use, and exacerbations. Of 5,311 eligible subjects, 2,057 initiated LAMA therapy (LAMA cohort) and 191 initiated LAMA+LABA therapy (LAMA+LABA cohort). The Charlson comorbidity index was slightly lower in the LAMA+LABA cohort than the LAMA cohort (mean±SD: 0.63±1.13 vs. 0.66±1.28), but the number of prescriptions was higher (mean±SD: 42.9±23.2 vs. 30.5±27.2). The LAMA+LABA cohort had higher short-acting inhaled β2 agonist (56.0% vs. 35.7%), oral corticosteroid (37.7% vs. 32.6%), and home oxygen therapy use (14.1% vs. 3.2%) than the LAMA cohort. Total medical costs were greater in the LAMA+LABA cohort than the LAMA cohort (mean±SD: $3,320.40±4085.9 vs. $1,226.20±3602.9), although emergency department ($11.00±66.8 vs. $30.70±259.2) and outpatient visit ($39.60±163.1 vs. $41.70±424.3) costs were lower. Resource use and exacerbation incidence were similar between cohorts. In this first look, subjects with COPD initiating LAMA or LAMA+LABA therapy exhibited different clinical and resource use characteristics in the year before treatment. Subjects receiving LAMA+LABA were older, with higher COPD co-medication use, more prescriptions, and associated higher pharmacy costs compared with subjects initiating LAMA. These differences may reflect a higher severity of COPD in those starting LABA+LAMA treatment.

Assessing the Potential for Bias From Nonresponse to a Study Follow-up Interview: An Example From the Agricultural Health Study.

PubMed

Rinsky, Jessica L; Richardson, David B; Wing, Steve; Beard, John D; Alavanja, Michael; Beane Freeman, Laura E; Chen, Honglei; Henneberger, Paul K; Kamel, Freya; Sandler, Dale P; Hoppin, Jane A

2017-08-15

Prospective cohort studies are important tools for identifying causes of disease. However, these studies are susceptible to attrition. When information collected after enrollment is through interview or exam, attrition leads to missing information for nonrespondents. The Agricultural Health Study enrolled 52,394 farmers in 1993-1997 and collected additional information during subsequent interviews. Forty-six percent of enrolled farmers responded to the 2005-2010 interview; 7% of farmers died prior to the interview. We examined whether response was related to attributes measured at enrollment. To characterize potential bias from attrition, we evaluated differences in associations between smoking and incidence of 3 cancer types between the enrolled cohort and the subcohort of 2005-2010 respondents, using cancer registry information. In the subcohort we evaluated the ability of inverse probability weighting (IPW) to reduce bias. Response was related to age, state, race/ethnicity, education, marital status, smoking, and alcohol consumption. When exposure and outcome were associated and case response was differential by exposure, some bias was observed; IPW conditional on exposure and covariates failed to correct estimates. When response was nondifferential, subcohort and full-cohort estimates were similar, making IPW unnecessary. This example provides a demonstration of investigating the influence of attrition in cohort studies using information that has been self-reported after enrollment. © The Author(s) 2017. 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.

Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies.

PubMed

Azad, Meghan B; Abou-Setta, Ahmed M; Chauhan, Bhupendrasinh F; Rabbani, Rasheda; Lys, Justin; Copstein, Leslie; Mann, Amrinder; Jeyaraman, Maya M; Reid, Ashleigh E; Fiander, Michelle; MacKay, Dylan S; McGavock, Jon; Wicklow, Brandy; Zarychanski, Ryan

2017-07-17

Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects. We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points. From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference -0.37 kg/m 2 ; 95% confidence interval [CI] -1.10 to 0.36; I 2 9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06; I 2 0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome. Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners. Protocol registration: PROSPERO-CRD42015019749. © 2017 Canadian Medical Association or its licensors.

NF1 truncating mutations associated to aggressive clinical phenotype with elephantiasis neuromatosa and solid malignancies.

PubMed

Ponti, Giovanni; Martorana, Davide; Pellacani, Giovanni; Ruini, Cristel; Loschi, Pietro; Baccarani, Alessio; De Santis, Giorgio; Pollio, Annamaria; Neri, Tauro Maria; Mandel, Victor Desmond; Maiorana, Antonio; Maccio, Livia; Maccaferri, Monia; Tomasi, Aldo

2014-06-01

Von Recklinghausen disease is a syndrome characterized by a wide phenotypic variability giving rise to both, cutaneous and visceral benign and malignant neoplasms. The first include cutaneous neurofibromas, subcutaneous and plexiform neurofibromas. The latter can undergo malignant transformation and/or determine elephantiasis neuromatosa. Visceral tumors may include malignant peripheral nerve sheet tumors, gastrointestinal stromal tumors, cerebral gliomas and abdominal neurofibromas. In the present study, the authors discuss the clinical and biomolecular characterization of a cohort of 20 families with a diagnosis of type 1 neurofibromatosis. Clinically, the cohort includes three probands with elephantiasis neuromatosa and a peculiarly high incidence of breast and gastrointestinal cancer. Among the 14 NF1 mutations documented, 10 encoding for a truncated protein have been associated to particularly aggressive clinical phenotypes including elephantiasis neuromatosa, malignant peripheral nerve sheet tumors, breast cancer, gastrointestinal stromal tumors. This effect on protein synthesis, rather than the type of NF1 mutation, is the key to the explanation of the genotype-phenotype correlations in the context of neurofibromatosis type 1. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

A[Beta] Deposits in Older Non-Demented Individuals with Cognitive Decline Are Indicative of Preclinical Alzheimer's Disease

ERIC Educational Resources Information Center

Villemagne, V. L.; Pike, K. E.; Darby, D.; Maruff, P.; Savage, G.; Ng, S.; Ackermann, U.; Cowie, T. F.; Currie, J.; Chan, S. G.; Jones, G.; Tochon-Danguy, H.; O'Keefe, G.; Masters, C. L.; Rowe, C. C.

2008-01-01

Approximately 30% of healthy persons aged over 75 years show A[beta] deposition at autopsy. It is postulated that this represents preclinical Alzheimer's disease (AD). We evaluated the relationship between A[beta] burden as assessed by PiB PET and cognitive decline in a well-characterized, non-demented, elderly cohort. PiB PET studies and…

Characterization of African Human Retroviruses Related to HTLV-III/LAV

DTIC Science & Technology

1988-06-15

the prototype AIDS virus , HIV -1 (4,5). This new human retrovirus has now been termed Human Immunodeficiency Virus Type...lImmunodeficiency Virus and its Relationship to the Human Immunodeficiency Viruses . Nature 32:539-543, 1987. (12) Guyader, M., Emerman, M., Sonigo, P...populations the number of AIDS cases is still quite low suggesting a distinct pathobiology to this new human retrovirus . Cohort studies of

Development of Advanced Technologies for Complete Genomic and Proteomic Characterization of Quantized Human Tumor Cells

DTIC Science & Technology

2015-09-01

glioblastoma . We have successfully established several patient-derived cell lines from glioblastoma tumors and further established a number of...and single-cell technologies. Although the focus of this research is glioblastoma , the proposed tools are generally applicable to all cancer-based...studies. 15. SUBJECT TERMS Human cohorts, Glioblastoma , Genomic, Proteomic, Single-cell technologies, Hypothesis-driven, integrative systems approach

Longitudinal associations between different dementia diagnoses and medication use jointly accounting for dropout.

PubMed

Agogo, George O; Ramsey, Christine M; Gnjidic, Danijela; Moga, Daniela C; Allore, Heather

2018-04-18

ABSTRACTBackground:Longitudinal studies of older adults are characterized by high dropout rates, multimorbid conditions, and multiple medication use, especially proximal to death. We studied the association between multiple medication use and incident dementia diagnoses including Alzheimer's disease (AD), vascular dementia (VD), and Lewy-body dementia (LBD), simultaneously accounting for dropout. Using the National Alzheimer's Coordinating Center data with three years of follow-up, a set of covariate-adjusted models that ignore dropout was fit to complete-case data, and to the whole-cohort data. Additionally, covariate-adjusted joint models with shared random effects accounting for dropout were fit to the whole-cohort data. Multiple medication use was defined as polypharmacy (⩾ five medications), hyperpolypharmacy (⩾ ten medications), and total number of medications. Incident diagnoses were 2,032 for AD, 135 for VD, and 139 for LBD. Percentages of dropout at the end of follow-up were as follows: 71.8% for AD, 81.5% for VD, and 77.7% for LBD. The odds ratio (OR) estimate for hyperpolypharmacy among those with LBD versus AD was 2.19 (0.78, 6.15) when estimated using complete-case data and 3.00 (1.66, 5.40) using whole-cohort data. The OR reduced to 1.41 (0.76, 2.64) when estimated from the joint model accounting for dropout. The OR for polypharmacy using complete-case data differed from the estimates using whole-cohort data. The OR for dementia diagnoses on total number of medications was similar, but non-significant when estimated using complete-case data. Reasons for dropout should be investigated and appropriate statistical methods should be applied to reduce bias in longitudinal studies among high-risk dementia cohorts.

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

PubMed

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

2015-07-01

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

Quantitative cancer risk assessment based on NIOSH and UCC epidemiological data for workers exposed to ethylene oxide.

PubMed

Valdez-Flores, Ciriaco; Sielken, Robert L; Teta, M Jane

2010-04-01

The most recent epidemiological data on individual workers in the NIOSH and updated UCC occupational studies have been used to characterize the potential excess cancer risks of environmental exposure to ethylene oxide (EO). In addition to refined analyses of the separate cohorts, power has been increased by analyzing the combined cohorts. In previous SMR analyses of the separate studies and the present analyses of the updated and pooled studies of over 19,000 workers, none of the SMRs for any combination of the 12 cancer endpoints and six sub-cohorts analyzed were statistically significantly greater than one including the ones of greatest previous interest: leukemia, lymphohematopoietic tissue, lymphoid tumors, NHL, and breast cancer. In our study, no evidence of a positive cumulative exposure-response relationship was found. Fitted Cox proportional hazards models with cumulative EO exposure do not have statistically significant positive slopes. The lack of increasing trends was corroborated by categorical analyses. Cox model estimates of the concentrations corresponding to a 1-in-a-million extra environmental cancer risk are all greater than approximately 1ppb and are more than 1500-fold greater than the 0.4ppt estimate in the 2006 EPA draft IRIS risk assessment. The reasons for this difference are identified and discussed. Copyright 2009 Elsevier Inc. All rights reserved.

The kynurenine pathway is activated in human obesity and shifted toward kynurenine monooxygenase activation.

PubMed

Favennec, Marie; Hennart, Benjamin; Caiazzo, Robert; Leloire, Audrey; Yengo, Loïc; Verbanck, Marie; Arredouani, Abdelilah; Marre, Michel; Pigeyre, Marie; Bessede, Alban; Guillemin, Gilles J; Chinetti, Giulia; Staels, Bart; Pattou, François; Balkau, Beverley; Allorge, Delphine; Froguel, Philippe; Poulain-Godefroy, Odile

2015-10-01

This study characterized the kynurenine pathway (KP) in human obesity by evaluating circulating levels of kynurenines and the expression of KP enzymes in adipose tissue. Tryptophan and KP metabolite levels were measured in serum of individuals from the D.E.S.I.R. cohort (case-cohort study: 212 diabetic, 836 randomly sampled) and in women with obesity, diabetic or normoglycemic, from the ABOS cohort (n = 100). KP enzyme gene expressions were analyzed in omental and subcutaneous adipose tissue of women from the ABOS cohort, in human primary adipocytes and in monocyte-derived macrophages. In the D.E.S.I.R. cohort, kynurenine levels were positively associated with body mass index (BMI) (P = 4.68 × 10(-19) ) and with a higher HOMA2-IR insulin resistance index (P = 6.23 × 10(-4) ). The levels of kynurenine, kynurenic acid, and quinolinic acid were associated with higher BMI (P < 0.05). The expression of several KP enzyme genes (indoleamine 2,3-dioxygenase 1 [IDO1], kynureninase [KYNU], kynurenine 3-monooxygenase [KMO], and kynurenine aminotransferase III [CCBL2]) was increased in the omental adipose tissue of women with obesity compared to lean (P < 0.05), and their expression was induced by proinflammatory cytokines in human primary adipocytes (P < 0.05), except for KMO that is not expressed in these cells. The expressions of IDO1, KYNU, KMO, and CCBL2 were higher in proinflammatory than in anti-inflammatory macrophages (P < 0.05). In the context of obesity, the presence of macrophages in adipose tissue may contribute to diverting KP toward KMO activation. © 2015 The Obesity Society.

Demographics and co-occurring conditions in a clinic-based cohort with Down syndrome in the United Arab Emirates.

PubMed

Corder, Jennifer Price; Al Ahbabi, Fatima Jaber Sehmi; Al Dhaheri, Hind Saif; Chedid, Fares

2017-09-01

The majority of studies describing demographics and co-occurring conditions in cohorts with Down syndrome come from regions outside of the Middle East, mainly from Europe and North America. This paper describes demographics and co-occurring conditions in a hospital-based cohort of individuals with Down syndrome living in the Middle Eastern country of the United Arab Emirates (UAE). The first dedicated Down syndrome clinic in the UAE was established in 2012 at Tawam Hospital in Al Ain. This paper describes a clinic-based cohort of 221 participants over 4 years from the Gulf Down Syndrome Registry, a new Down syndrome database and contact registry created at Tawam Hospital. Key demographic findings include mean maternal age of 37 years, among the highest described in the literature. Sixty-two percent of mothers are >35 years. Over 90% of mothers received post-natal diagnosis of Down syndrome. High sex ratio, parental consanguinity, and large family size also characterize the group. The spectrum of many co-occurring conditions mirrors that of previously described populations, with some notable differences. Cardiovascular malformations are well represented, however, atrioventricular canal is not the most common. Genitourinary conditions are common, as evidenced by 12% of males with hypospadias and 15% with undescended testes. Glucose-6-phosphate dehydrogenase deficiency, alpha thalassemia trait, hypovitaminosis D, and dental caries are common in our cohort. This study describes a large hospital-based group with Down syndrome presenting to a new dedicated Down syndrome clinic in the UAE, highlighting unique demographic and co-occurring conditions found in that population. © 2017 Wiley Periodicals, Inc.

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

Over-representation of the APOE*4 allele in autopsy confirmed early- and late-onset sporadic Alzheimer`s disease

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

Kamboh, M.I.; DeKosky, S.T.; Ferrell, R.E.

1994-09-01

Apolipoprotein E binds to {beta}-amyloid peptide in senile plaques and neurofibrillary tangles in Alzheimer`s disease (AD). Recent studies have identified the APOE*4 allele as a major predisposing genetic factor for late-onset familial AD as well as in sporadic AD. Most of these association studies are based on clinically diagnosed AD cases with little data available on autopsy confirmed, definite AD. To characterize the distribution of APOE polymorphism in autopsy confirmed sporadic AD cases, we determined APOE genotypes in 111 DNA samples (aged 51-101 years) extracted from brain tissues which were available from the University of Pittsburgh Alzheimer`s Disease Research Center.more » The APOE data was compared between the AD group and 3 samples of population controls from Western Pennsylvania consisting of a young cohort (N=473, aged 18-48 years), middle cohort (N=473, aged 42-50 years) and an old cohort (N=870, aged 65-90 years). The frequency of the APOE*4 allele was similar in the young and middle cohorts (0.12) and slightly lower in the old cohort (0.10). However, the frequency of the APOE*4 allele was three times higher in both early-onset (<65 years; 0.36) and late-onset ({ge}65 years; 0.38) sporadic AD cases compared to the control groups (p<0.0001). In the AD cohort the frequency of the APOE*4 allele was similar across all age groups (<65, 65-75, 76-85, 86+) and so was in men and women (0.40 vs. 0.37). The E*4 homozygosity was observed in 18% of AD cases compared to 1% in each of the three control groups. The E*4 heterozygosity was present in 50% of AD cases compared to 17% in the control old cohort and 22% in both the young and middle control cohorts. These data confirm that the APOE*4 allele is a major risk factor for AD regardless of age-at-diagnosis or family history.« less

Candidemia in the intensive care unit: A 12-year retrospective cohort study in Reunion Island.

PubMed

Hoarau, G; Picot, S; Lemant, J; Peytral, J; Poubeau, P; Zunic, P; Mohr, C; Coueffe, X; Gerardin, P; Antok, E

2018-05-09

We aimed to describe the epidemiology of Candida bloodstream infection in an intensive care unit (ICU) in Reunion Island. We performed a retrospective cohort study and evaluated 63 candidemia episodes, which occurred between January 2004 and December 2015 in the ICU of a University Hospital in St-Pierre. The incidence rate of candidemia in the ICU was estimated at 7.6%. Candida albicans was the most common yeast pathogen species recovered (54%), followed by Candida glabrata (17%), Candida tropicalis (12%) and Candida parapsilosis (10%). Between 2012 and 2015, we also observed a modification of antifungal use. The epidemiology of candidemia in Reunion Island is characterized by the predominance of Candida albicans and by the relative importance of Candida tropicalis. This pattern corresponds to a model of epidemiological transition between the one usually observed in tropical areas and the one observed in temperate countries. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Using NASA Remotely Sensed Data to Help Characterize Environmental Risk Factors for National Public Health Applications

NASA Technical Reports Server (NTRS)

Al-Hamdan, Mohammad; Crosson, William; Estes, Maury; Estes, Sue; Hemmings, Sarah; Quattrochi, Dale; McClure, Keslie; Kent, Shia; Economou, Sigrid; Puckett, Mark;

Characterization of Death in Neonatal Encephalopathy in the Hypothermia Era.

PubMed

Lemmon, Monica E; Boss, Renee D; Bonifacio, Sonia L; Foster-Barber, Audrey; Barkovich, A James; Glass, Hannah C

2017-03-01

This study aimed to characterize the circumstances of death in encephalopathic neonates treated with therapeutic hypothermia. Patients who died after or during treatment with therapeutic hypothermia between 2007-2014 were identified. Patient circumstance of death was characterized using an established paradigm. Thirty-one of 229 patients died (14%) at a median of 3 days of life. Most who died were severely encephalopathic on examination (90%) and had severely abnormal electroencephalographic (EEG) findings (87%). All those who had magnetic resonance images (n = 13) had evidence of moderate-severe brain injury; 6 had near-total brain injury. Cooling was discontinued prematurely in 61% of patients. Most patients (90%) were physiologically stable at the time of death; 81% died following elective extubation for quality of life considerations. Three patients (10%) died following withholding or removal of artificial hydration and nutrition. Characterization of death in additional cohorts is needed to identify differences in decision making practices over time and between centers.

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma.

PubMed

Aguiar, João P; Cardoso Borges, Fábio; Murteira, Rodrigo; Ramos, Catarina; Gouveia, Emanuel; Passos, Maria José; Miranda, Ana; da Costa, Filipa Alves

2018-06-02

Background Toxicity of oncology treatments in real-life patients is frequently disregarded and hence underreported. Objective To characterize adverse events (AEs) of immunotherapy and targeted therapy reported in patients with locally advanced or metastatic melanoma. Setting District Hospital for Cancer treatment (Instituto Português de Oncologia de Lisboa Francisco Gentil). Method A retrospective cohort of melanoma patients was established, comprising adult patients diagnosed with malignant melanoma treated with immunotherapy or targeted therapy. Exposure was characterized by nature, time and intensity of exposure. To account for different exposure periods, person-time was used as unit of analysis. Main outcomes measure Occurrence of AEs. Results Data from 111 patients included in the cohort indicates the majority received immunotherapy regimens (CTLA-4, anti-PD-1 and combination therapy; (n = 70; 63.1%), among which anti-PD-1 were the predominant treatment. Pembrolizumab was the most frequently prescribed drug (n = 30; 45.7%). Three hundred and seventy-one AEs were extracted. The incidence of AEs was lower in the anti-PD-1 mAc group (54 AEs per 1000 person.months) and the number of AEs/patient was also lower (3.1 ± 2.0). Grade 3 to 4 AEs occurred in 15.3% (n = 17) of the cohort, being more common in the targeted therapy group. Forty-two (11.6%) of the extracted AEs were not described in the Summary of Product Characteristics of the drugs under study. Conclusion This study suggests various known and unknown AEs of immunotherapy and targeted therapy may be identified using the Cancer Registry database. These events should be considered as signals worth further investigation for assessment of causality as the underreporting of AEs in cancer may have potential implications for the patient's quality of life.

Breathing pattern and breathlessness in idiopathic pulmonary fibrosis: An observational study.

PubMed

Olukogbon, Kasope L; Thomas, Paul; Colasanti, Ricardo; Hope-Gill, Ben; Williams, Edgar Mark

2016-02-01

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive decline in lung function and increasing dyspnoea. The aim of this study was to investigate the relationship among IPF, pulmonary function, resting tidal breathing patterns and level of breathlessness. Thirty-one participants with IPF and 17 matched healthy controls underwent lung function testing, followed by a 2-min period of resting tidal breathing. The IPF cohort was stratified according to disease severity, based on their forced vital capacity and diffusion capacity for carbon monoxide. In comparison to the healthy controls, the IPF cohort showed a higher tidal volume, VT , of 0.22 L (P = 0.026) and a raised minute ventilation in the severest IPF group, while no differences in the timing of inspiration or expiration were observed. In the IPF cohort, the ratio of VT to forced vital capacity was around 15% higher. These changes corresponded with an increase in the self-reported sensation of breathlessness. Those with IPF increased their depth of breathing with worsening disease severity, with IPF-induced changes in pulmonary function and breathlessness associated with an altered tidal breathing pattern. © 2015 Asian Pacific Society of Respirology.

Preclinical Mouse Models of Neurofibromatosis

DTIC Science & Technology

2005-11-01

and NF2-deficient human cells and in cells from Nf1 and Nf2 mutant mice. Genetic analysis of human and murine tumors has provided compelling...lethal myeloproliferative disorder (MPD) characterized by over-production of infiltrative myeloid cells (13). JMML has been modeled in mice by...tumor development for 18 months after exposure. Pathologic analysis was performed on 91% of the Shannon, K.M. 11 study cohort, including 95 of 104

Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy.

PubMed

Iarossi, Giancarlo; Bertelli, Matteo; Maltese, Paolo Enrico; Gusson, Elena; Marchini, Giorgio; Bruson, Alice; Benedetti, Sabrina; Volpetti, Sabrina; Catena, Gino; Buzzonetti, Luca; Ziccardi, Lucia

2017-01-01

Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7-19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4 , LRP5 , TSPAN12 , and NDP . Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands ( NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family.

Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy

PubMed Central

Marchini, Giorgio; Volpetti, Sabrina; Catena, Gino

2017-01-01

Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7–19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4, LRP5, TSPAN12, and NDP. Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands (NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family. PMID:28758032

Advantages and pitfalls of an extended gene panel for investigating complex neurometabolic phenotypes.

PubMed

Reid, Emma S; Papandreou, Apostolos; Drury, Suzanne; Boustred, Christopher; Yue, Wyatt W; Wedatilake, Yehani; Beesley, Clare; Jacques, Thomas S; Anderson, Glenn; Abulhoul, Lara; Broomfield, Alex; Cleary, Maureen; Grunewald, Stephanie; Varadkar, Sophia M; Lench, Nick; Rahman, Shamima; Gissen, Paul; Clayton, Peter T; Mills, Philippa B

2016-11-01

Neurometabolic disorders are markedly heterogeneous, both clinically and genetically, and are characterized by variable neurological dysfunction accompanied by suggestive neuroimaging or biochemical abnormalities. Despite early specialist input, delays in diagnosis and appropriate treatment initiation are common. Next-generation sequencing approaches still have limitations but are already enabling earlier and more efficient diagnoses in these patients. We designed a gene panel targeting 614 genes causing inborn errors of metabolism and tested its diagnostic efficacy in a paediatric cohort of 30 undiagnosed patients presenting with variable neurometabolic phenotypes. Genetic defects that could, at least partially, explain observed phenotypes were identified in 53% of cases. Where biochemical abnormalities pointing towards a particular gene defect were present, our panel identified diagnoses in 89% of patients. Phenotypes attributable to defects in more than one gene were seen in 13% of cases. The ability of in silico tools, including structure-guided prediction programmes to characterize novel missense variants were also interrogated. Our study expands the genetic, clinical and biochemical phenotypes of well-characterized (POMGNT1, TPP1) and recently identified disorders (PGAP2, ACSF3, SERAC1, AFG3L2, DPYS). Overall, our panel was accurate and efficient, demonstrating good potential for applying similar approaches to clinically and biochemically diverse neurometabolic disease cohorts. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Characterizing the genetic risk for Type 2 diabetes in a Malaysian multi-ethnic cohort.

PubMed

Abdullah, N; Abdul Murad, N A; Attia, J; Oldmeadow, C; Mohd Haniff, E A; Syafruddin, S E; Abd Jalal, N; Ismail, N; Ishak, M; Jamal, R; Scott, R J; Holliday, E G

2015-10-01

To characterize the association with Type 2 diabetes of known Type 2 diabetes risk variants in people in Malaysia of Malay, Chinese and Indian ancestry who participated in the Malaysian Cohort project. We genotyped 1604 people of Malay ancestry (722 cases, 882 controls), 1654 of Chinese ancestry (819 cases, 835 controls) and 1728 of Indian ancestry (851 cases, 877 controls). First, 62 candidate single-nucleotide polymorphisms previously associated with Type 2 diabetes were assessed for association via logistic regression within ancestral groups and then across ancestral groups using a meta-analysis. Second, estimated odds ratios were assessed for excess directional concordance with previously studied populations. Third, a genetic risk score aggregating allele dosage across the candidate single-nucleotide polymorphisms was tested for association within and across ancestral groups. After Bonferroni correction, seven individual single-nucleotide polymorphisms were associated with Type 2 diabetes in the combined Malaysian sample. We observed a highly significant excess in concordance of effect directions between Malaysian and previously studied populations. The genetic risk score was strongly associated with Type 2 diabetes in all Malaysian groups, explaining from 1.0 to 1.7% of total Type 2 diabetes risk variance. This study suggests there is substantial overlap of the genetic risk alleles underlying Type 2 diabetes in Malaysian and other populations. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Characterization of particulate and gas exposures of sensitive subpopulations living in Baltimore and Boston.

PubMed

Koutrakis, Petros; Suh, Helen H; Sarnat, Jeremy A; Brown, Kathleen Ward; Coull, Brent A; Schwartz, Joel

2005-12-01

Personal exposures to particulate and gaseous pollutants and corresponding ambient concentrations were measured for 56 subjects living in Baltimore, Maryland, and 43 subjects living in Boston, Massachusetts. The 3 Baltimore cohorts consisted of 20 healthy older adults (seniors), 21 children, and 15 individuals with physician-diagnosed chronic obstructive pulmonary disease (COPD*). The 2 Boston cohorts were 20 healthy seniors and 23 children. All children were 9 to 13 years of age; seniors were 65 years of age or older; and the COPD participants had moderate to severe physician-diagnosed COPD. Personal exposures to particulate matter with aerodynamic diameters less than 2.5 microm (PM2.5), sulfate (SO(4)2-), elemental carbon (EC), ozone (03), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were measured simultaneously for 24 hours/day. All subjects were monitored for 8 to 12 consecutive days. The primary objectives of this study were (1) to characterize the personal particulate and gaseous exposures for individuals sensitive to PM health effects and (2) to assess the appropriateness of exposure assessment strategies for use in PM epidemiologic studies. Personal exposures to multiple pollutants and ambient concentrations were measured for subjects from each cohort from each location. Pollutant data were analyzed using correlation and mixed-model regression analyses. In Baltimore, personal PM2.5 exposures tended to be comparable to (and frequently lower than) corresponding ambient concentrations; in Boston, the personal exposures were frequently higher. Overall, personal exposures to the gaseous pollutants, especially O3 and SO2, were considerably lower than corresponding ambient concentrations because of the lack of indoor sources for these gases and their high removal rate on indoor surfaces. Further, the impact of ambient particles on personal exposure (the infiltration factor) and differences in infiltration factor by city, season, and cohort were investigated. No difference in infiltration factor was found among the cohorts, which suggests that all subjects were exposed to the same fraction of ambient PM2.5 for a given ambient concentration. In addition, the results show significant correlations between ambient PM2.5 concentrations and corresponding personal exposures over time and provide further indication that ambient gaseous pollutant concentrations may be better surrogates for personal PM2.5 exposures, especially personal exposures to PM2.5 of ambient origin, than their respective personal exposures. These results have important implications for PM health effects studies that use regression models including both ambient PM2.5 and gaseous pollutant concentrations as independent variables, because both parameters may be serving as surrogates for PM2.5 exposures.

The Kidney Outcomes Prediction and Evaluation (KOPE) study: a prospective cohort investigation of patients undergoing hemodialysis. Study design and baseline characteristics.

PubMed

Sevick, M A; Tell, G S; Shumaker, S A; Rocco, M V; Burkart, J M; Rushing, J T; Levine, D W; Chen, J; Bradham, D D; Pierce, J J; James, M K

1998-04-01

The purpose of the Kidney Outcomes Prediction and Evaluation (KOPE) study, was to more fully characterize the end-stage renal disease (ESRD) population with respect to social, psychological, and clinical characteristics, and to prospectively study the biomedical, social, and psychological factors that influence a range of ESRD outcomes in a large observational study of black and white patients on hemodialysis. This paper focuses on the KOPE study design as well as characteristics of patients at baseline. KOPE was a prospective cohort investigation of patients treated at four dialysis centers in Forsyth County, North Carolina. Participants were interviewed at the dialysis centers, semi-annually over a 3 1/2 year period. Prevalent cases who were being treated with hemodialysis at the initiation of the study were enrolled into KOPE. Incident cases were subsequently enrolled as they presented to the participating units for hemodialysis. A total of 304 prevalent and 162 incident cases were enrolled into the study. The baseline health and sociodemographic characteristics of KOPE participants reported in this paper were obtained from medical records and Southeast Kidney Council data. Laboratory values taken within a 30-day interval around the baseline interview are also reported. KOPE participants differ from national statistics on race, age, and gender. Differences between KOPE participants and patients living in the region, but who did not participate in the study, can be explained by our recruitment criteria. KOPE will enable the characterization of the ESRD population, identification of factors related to poor outcomes, and identification of opportunities for interventions to prevent death and morbidity.

Rationale and design of a multicenter echocardiographic study to assess the relationship between cardiac structure and function and heart failure risk in a biracial cohort of community-dwelling elderly persons: the Atherosclerosis Risk in Communities study.

PubMed

Shah, Amil M; Cheng, Susan; Skali, Hicham; Wu, Justina; Mangion, Judy R; Kitzman, Dalane; Matsushita, Kunihiro; Konety, Suma; Butler, Kenneth R; Fox, Ervin R; Cook, Nakela; Ni, Hanyu; Coresh, Josef; Mosley, Thomas H; Heiss, Gerardo; Folsom, Aaron R; Solomon, Scott D

2014-01-01

Heart failure is an important public health concern, particularly among persons>65 years of age. Women and blacks are critically understudied populations that carry a sizeable portion of the heart failure burden. Limited normative and prognostic data exist on measures of cardiac structure, diastolic function, and novel measures of systolic deformation in older adults living in the community. The Atherosclerosis Risk in Communities (ARIC) study is a large, predominantly biracial, National Heart, Lung, and Blood Institute-sponsored epidemiological cohort study. Between 2011 and 2013, ≈6000 surviving participants, now in their seventh to ninth decade of life, are expected to return for a fifth study visit during which comprehensive 2-dimensional, Doppler, tissue Doppler, and speckle-tracking echocardiography will be performed uniformly in all cohort clinic visit participants. The following objectives will be addressed: (1) to characterize cardiac structural and functional abnormalities among the elderly and to determine how they differ by sex and race/ethnicity, (2) to determine the relationship between ventricular and vascular abnormalities, and (3) to prospectively examine the extent to which these noninvasive measures associate with incident heart failure. We describe the design, imaging acquisition and analysis methods, and quality assurance metrics for echocardiography in visit 5 of the ARIC cohort. A better understanding of the differences in cardiac structure and function through the spectrum of heart failure stages in elderly persons generally, and between sexes and racial/ethnic groups specifically, will deepen our understanding of the pathophysiology driving heart failure progression in these at-risk populations and may inform novel prevention or therapeutic strategies.

Association between hypoglycaemia and impaired hypoglycaemia awareness and mortality in people with Type 1 diabetes mellitus.

PubMed

Sejling, A-S; Schouwenberg, B; Faerch, L H; Thorsteinsson, B; de Galan, B E; Pedersen-Bjergaard, U

2016-01-01

To examine whether severe hypoglycaemia and impaired hypoglycaemic awareness, a principal predictor of severe hypoglycaemia, are associated with all-cause mortality or cardiovascular mortality in Type 1 diabetes mellitus. Mortality was recorded in two cohorts, one in Denmark (n = 269, follow-up 12 years) and one in the Netherlands (n = 482, follow-up 6.5 years). In both cohorts, awareness class was characterized and numbers of episodes of severe hypoglycaemia either during lifetime (Danish cohort) or during the preceding year (Dutch cohort) were recorded. In addition, episodes of severe hypoglycaemia were prospectively recorded every month for 1 year in the Danish cohort. Follow-up data regarding mortality were obtained through medical reports and registries (Danish cohort). All-cause mortality was 14% (n = 39) in the Danish and 4% (n = 20) in the Dutch cohort. In either cohort, neither presence of episodes with severe hypoglycaemia nor impaired hypoglycaemia awareness were associated with increased mortality in age-truncated Cox proportional hazard regression models. Variables associated with increased risk of all-cause mortality in both cohorts were evidence of macrovascular disease and reduced kidney function. Severe hypoglycaemia and hypoglycaemia unawareness are not associated with increased risk of all-cause or cardiovascular mortality in people with Type 1 diabetes mellitus. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

An International Survey of Brain Banking Operation and Characterization Practices

PubMed Central

Palmer-Aronsten, Beatrix; McCrossin, Toni; Kril, Jillian

2016-01-01

Brain banks continue to make a major contribution to the study of neurological and psychiatric disorders. The current complexity and scope of research heighten the need for well-characterized cases and the demand for larger cohorts and necessitate strategies, such as the establishment of bank networks based in regional areas. While individual brain banks have developed protocols that meet researchers' needs within the confines of resources and funding, to further promote collaboration, standardization and scientific validity and understanding of the current protocols of participating banks are required. A survey was sent to brain banks, identified by an Internet search, to investigate operational protocols, case characterization, cohort management, data collection, standardization, and degree of collaboration between banks. The majority of the 24 banks that returned the survey have been established for more than 20 years, and most are affiliated with a regional network. While prospective donor programs were the primary source of donation, the data collected on donors varied. Longitudinal information assists case characterization and enhances the analysis capabilities of research. However, acquiring this information depended on the availability of qualified staff. Respondents indicated a high level of importance for standardization, but only 8 of 24 considered this occurred between banks. Standard diagnostic criteria were not achieved in the classification of controls, and some banks relied on the researcher to indicate the criteria for classification of controls. Although the capacity to collaborate with other banks was indicated by 16 of 24 banks, this occurred infrequently. Engagement of all brain banks to participate toward a consensus of diagnostic tools, especially for controls, will strengthen collaboration. PMID:27399803

An International Survey of Brain Banking Operation and Characterization Practices.

PubMed

Palmer-Aronsten, Beatrix; Sheedy, Donna; McCrossin, Toni; Kril, Jillian

2016-12-01

Brain banks continue to make a major contribution to the study of neurological and psychiatric disorders. The current complexity and scope of research heighten the need for well-characterized cases and the demand for larger cohorts and necessitate strategies, such as the establishment of bank networks based in regional areas. While individual brain banks have developed protocols that meet researchers' needs within the confines of resources and funding, to further promote collaboration, standardization and scientific validity and understanding of the current protocols of participating banks are required. A survey was sent to brain banks, identified by an Internet search, to investigate operational protocols, case characterization, cohort management, data collection, standardization, and degree of collaboration between banks. The majority of the 24 banks that returned the survey have been established for more than 20 years, and most are affiliated with a regional network. While prospective donor programs were the primary source of donation, the data collected on donors varied. Longitudinal information assists case characterization and enhances the analysis capabilities of research. However, acquiring this information depended on the availability of qualified staff. Respondents indicated a high level of importance for standardization, but only 8 of 24 considered this occurred between banks. Standard diagnostic criteria were not achieved in the classification of controls, and some banks relied on the researcher to indicate the criteria for classification of controls. Although the capacity to collaborate with other banks was indicated by 16 of 24 banks, this occurred infrequently. Engagement of all brain banks to participate toward a consensus of diagnostic tools, especially for controls, will strengthen collaboration.

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

Hair toxic and essential trace elements in children with autism spectrum disorder.

PubMed

Skalny, Anatoly V; Simashkova, Natalia V; Klyushnik, Tatiana P; Grabeklis, Andrei R; Bjørklund, Geir; Skalnaya, Margarita G; Nikonorov, Alexandr A; Tinkov, Alexey A

2017-02-01

The objective of the study was to investigate hair trace elements content in children suffering from autism spectrum disorder (ASD). A total of 74 ASD children and 74 sex- and age-matched controls divided into two age groups (2-4 and 5-9 years) were investigated. Hair trace elements content was assessed using inductively coupled plasma mass spectrometry. A general cohort of ASD children was characterized by 29 %, 41 %, and 24 % lower hair levels of chromium (Cr), iodine (I), and vanadium (V), respectively, whereas the level of selenium (Se) exceeded the respective control values by 31 %. In ASD children aged 2-4 years hair Cr, I and V content was 68 %, 36 % and 41 % lower than in the controls. Older ASD children were characterized by 45 % increase in hair Se levels. In a general cohort of ASD children hair beryllium (Be) and tin (Sn) levels were 50 % and 34 % lower than the control values. In the first age group (2-4 years) of ASD children 34 %, 42 %, and 73 % lower levels of arsenic (As), boron (B), and Be were detected. In the second age group of ASD children only a nearly significant 25 % decrease in hair lead (Pb) was detected. Surprisingly, no significant group difference in hair mercury (Hg), zinc (Zn), and copper (Cu) content was detected. Generally, the results of the present study demonstrate that children with ASD are characterized by lower values in hair of not only essential but also toxic trace elements.

GDNF Gene Is Associated With Tourette Syndrome in a Family Study

PubMed Central

Huertas-Fernández, Ismael; Gómez-Garre, Pilar; Madruga-Garrido, Marcos; Bernal-Bernal, Inmaculada; Bonilla-Toribio, Marta; Martín-Rodríguez, Juan Francisco; Cáceres-Redondo, María Teresa; Vargas-González, Laura; Carrillo, Fátima; Pascual, Alberto; Tischfield, Jay A.; King, Robert A.; Heiman, Gary A.; Mir, Pablo

2016-01-01

Background Tourette syndrome is a disorder characterized by persistent motor and vocal tics, and frequently accompanied by the comorbidities attention deficit hyperactivity disorder and obsessive-compulsive disorder. Impaired synaptic neurotransmission has been implicated in its pathogenesis. Our aim was to investigate the association of 28 candidate genes, including genes related to synaptic neurotransmission and neurotrophic factors, with Tourette syndrome. Methods We genotyped 506 polymorphisms in a discovery cohort from the United States composed of 112 families and 47 unrelated singletons with Tourette syndrome (201 cases and 253 controls). Genes containing significant polymorphisms were imputed to fine-map the signal(s) to potential causal variants. Allelic analyses in Tourette syndrome cases were performed to check the role in attention deficit hyperactivity disorder and obsessive-compulsive disorder comorbidities. Target polymorphisms were further studied in a replication cohort from southern Spain composed of 37 families and three unrelated singletons (44 cases and 73 controls). Results The polymorphism rs3096140 in glial cell line–derived neurotrophic factor gene (GDNF) was significant in the discovery cohort after correction (P = 1.5 × 10−4). No linkage disequilibrium was found between rs3096140 and other functional variants in the gene. We selected rs3096140 as target polymorphism, and the association was confirmed in the replication cohort (P = 0.01). No association with any comorbidity was found. Conclusions As a conclusion, a common genetic variant in GDNF is associated with Tourette syndrome. A defect in the production of GDNF could compromise the survival of parvalbumin interneurons, thus altering the excitatory/inhibitory balance in the corticostriatal circuitry. Validation of this variant in other family cohorts is necessary. PMID:26096985

GDNF gene is associated with tourette syndrome in a family study.

PubMed

Huertas-Fernández, Ismael; Gómez-Garre, Pilar; Madruga-Garrido, Marcos; Bernal-Bernal, Inmaculada; Bonilla-Toribio, Marta; Martín-Rodríguez, Juan Francisco; Cáceres-Redondo, María Teresa; Vargas-González, Laura; Carrillo, Fátima; Pascual, Alberto; Tischfield, Jay A; King, Robert A; Heiman, Gary A; Mir, Pablo

2015-07-01

Tourette syndrome is a disorder characterized by persistent motor and vocal tics, and frequently accompanied by the comorbidities attention deficit hyperactivity disorder and obsessive-compulsive disorder. Impaired synaptic neurotransmission has been implicated in its pathogenesis. Our aim was to investigate the association of 28 candidate genes, including genes related to synaptic neurotransmission and neurotrophic factors, with Tourette syndrome. We genotyped 506 polymorphisms in a discovery cohort from the United States composed of 112 families and 47 unrelated singletons with Tourette syndrome (201 cases and 253 controls). Genes containing significant polymorphisms were imputed to fine-map the signal(s) to potential causal variants. Allelic analyses in Tourette syndrome cases were performed to check the role in attention deficit hyperactivity disorder and obsessive-compulsive disorder comorbidities. Target polymorphisms were further studied in a replication cohort from southern Spain composed of 37 families and three unrelated singletons (44 cases and 73 controls). The polymorphism rs3096140 in glial cell line-derived neurotrophic factor gene (GDNF) was significant in the discovery cohort after correction (P = 1.5 × 10(-4) ). No linkage disequilibrium was found between rs3096140 and other functional variants in the gene. We selected rs3096140 as target polymorphism, and the association was confirmed in the replication cohort (P = 0.01). No association with any comorbidity was found. As a conclusion, a common genetic variant in GDNF is associated with Tourette syndrome. A defect in the production of GDNF could compromise the survival of parvalbumin interneurons, thus altering the excitatory/inhibitory balance in the corticostriatal circuitry. Validation of this variant in other family cohorts is necessary. © 2015 International Parkinson and Movement Disorder Society.

Gastroesophageal reflux disease and risk for bipolar disorder: a nationwide population-based study.

PubMed

Lin, Wan-Shan; Hu, Li-Yu; Liu, Chia-Jen; Hsu, Chih-Chao; Shen, Cheng-Che; Wang, Yen-Po; Hu, Yu-Wen; Tsai, Chia-Fen; Yeh, Chiu-Mei; Chen, Pan-Ming; Su, Tung-Ping; Chen, Tzeng-Ji; Lu, Ti

2014-01-01

Studies have shown that chronic inflammation may play a vital role in the pathophysiology of both gastroesophageal reflux disease (GERD) and bipolar disorder. Among patients with GERD, the risk of bipolar disorder has not been well characterized. We explored the relationship between GERD and the subsequent development of bipolar disorder, and examined the risk factors for bipolar disorder in patients with GERD. We identified patients who were diagnosed with GERD in the Taiwan National Health Insurance Research Database. A comparison cohort without GERD was matched according to age, sex, and comorbidities. The occurrence of bipolar disorder was evaluated in both cohorts based on diagnosis and the prescription of medications. The GERD cohort consisted of 21,674 patients, and the comparison cohort consisted of 21,674 matched control patients without GERD. The incidence of bipolar disorder (incidence rate ratio [IRR] 2.29, 95% confidence interval [CI] 1.58-3.36, P<.001) was higher among GERD patients than among comparison cohort. Multivariate, matched regression models showed that the female sex (hazard ratio [HR] 1.78, 95% CI 1.76-2.74, P = .008), being younger than 60 years old (HR 2.35, 95% CI 1.33-4.16, P = .003), and alcohol use disorder (HR 4.89, 95% CI 3.06-7.84, P = .004) were independent risk factors for the development of bipolar disorder among GERD patients. GERD may increase the risk of developing bipolar disorder. Based on our data, we suggest that attention should be focused on female patients younger than 60 years, and patients with alcohol use disorder, following a GERD diagnosis.

The Forgotten Learning Disability – Epidemiology of Written Language Disorder in a Population-Based Birth Cohort (1976-1982), Rochester, Minnesota

PubMed Central

Katusic, Slavica K.; Colligan, Robert C.; Weaver, Amy L.; Barbaresi, William J.

2009-01-01

OBJECTIVE The aim of this study was to report the incidence rates and other epidemiologic characterizations of Written Language Disorder (WLD). There have been no epidemiologic studies on the incidence of WLD in the United States and the use of a population-based birth cohort, longitudinally followed, is the most powerful method to reach this objective. METHODS In this population-based, retrospective birth cohort study, subjects included 5718 children born 1976-1982 in Rochester, Minnesota who remained in the community after age 5 years. Records from all public and nonpublic schools, medical facilities, and private tutorial services were reviewed and results of all individually administered IQ and achievement tests, and extensive medical, educational, and socioeconomic information were collected. The essential features of writing problems from the DSM-IV-TR were included in our operationalized definition of WLD. WLD incident cases were established using research criteria based on 3 formulas (regression-based discrepancy, non-regression-based discrepancy, low achievement). RESULTS Cumulative incidence rates of WLD varied from 6.9% to 14.7% depending on the formula. Boys were 2-3 times more likely to be affected than girls, regardless of the formula. Among all WLD cases (N=806), 25% (N=203) had WLD without Reading Disability (RD). Specifics of the writing problems were identified for 87% (N=702) of WLD cases. CONCLUSION In this population-based birth cohort of school aged children, WLD was at least as frequent as RD, and significantly more frequent among boys than girls. PMID:19403496

The UAE healthy future study: a pilot for a prospective cohort study of 20,000 United Arab Emirates nationals.

PubMed

Abdulle, Abdishakur; Alnaeemi, Abdullah; Aljunaibi, Abdullah; Al Ali, Abdulrahman; Al Saedi, Khaled; Al Zaabi, Eiman; Oumeziane, Naima; Al Bastaki, Marina; Al-Houqani, Mohammed; Al Maskari, Fatma; Al Dhaheri, Ayesha; Shah, Syed M; Loney, Tom; El-Sadig, Mohamed; Oulhaj, Abderrahim; Wareth, Leila Abdel; Al Mahmeed, Wael; Alsafar, Habiba; Hirsch, Benjamin; Al Anouti, Fatme; Yaaqoub, Jamila; Inman, Claire K; Al Hamiz, Aisha; Al Hosani, Ayesha; Haji, Muna; Alsharid, Teeb; Al Zaabi, Thekra; Al Maisary, Fatima; Galani, Divya; Sprosen, Tim; El Shahawy, Omar; Ahn, Jiyoung; Kirchhoff, Tomas; Ramasamy, Ravichandran; Schmidt, Ann Marie; Hayes, Richard; Sherman, Scott; Ali, Raghib

2018-01-05

The United Arab Emirates (UAE) is faced with a rapidly increasing burden of non-communicable diseases including obesity, diabetes, and cardiovascular disease. The UAE Healthy Future study is a prospective cohort designed to identify associations between risk factors and these diseases amongst Emiratis. The study will enroll 20,000 UAE nationals aged ≥18 years. Environmental and genetic risk factors will be characterized and participants will be followed for future disease events. As this was the first time a prospective cohort study was being planned in the UAE, a pilot study was conducted in 2015 with the primary aim of establishing the feasibility of conducting the study. Other objectives were to evaluate the implementation of the main study protocols, and to build adequate capacity to conduct advanced clinical laboratory analyses. Seven hundred sixty nine UAE nationals aged ≥18 years were invited to participate voluntarily in the pilot study. Participants signed an informed consent, completed a detailed questionnaire, provided random blood, urine, and mouthwash samples and were assessed for a series of clinical measures. All specimens were transported to the New York University Abu Dhabi laboratories where samples were processed and analyzed for routine chemistry and hematology. Plasma, serum, and a small whole blood sample for DNA extraction were aliquoted and stored at -80 °C for future analyses. Overall, 517 Emirati men and women agreed to participate (68% response rate). Of the total participants, 495 (95.0%), 430 (82.2%), and 492 (94.4%), completed the questionnaire, physical measurements, and provided biological samples, respectively. The pilot study demonstrated the feasibility of recruitment and completion of the study protocols for the first large-scale cohort study designed to identify emerging risk factors for the major non-communicable diseases in the region.

Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort.

PubMed

Meester, Josephina A N; Sukalo, Maja; Schröder, Kim C; Schanze, Denny; Baynam, Gareth; Borck, Guntram; Bramswig, Nuria C; Duman, Duygu; Gilbert-Dussardier, Brigitte; Holder-Espinasse, Muriel; Itin, Peter; Johnson, Diana S; Joss, Shelagh; Koillinen, Hannele; McKenzie, Fiona; Morton, Jenny; Nelle, Heike; Reardon, Willie; Roll, Claudia; Salih, Mustafa A; Savarirayan, Ravi; Scurr, Ingrid; Splitt, Miranda; Thompson, Elizabeth; Titheradge, Hannah; Travers, Colm P; Van Maldergem, Lionel; Whiteford, Margo; Wieczorek, Dagmar; Vandeweyer, Geert; Trembath, Richard; Van Laer, Lut; Loeys, Bart L; Zenker, Martin; Southgate, Laura; Wuyts, Wim

2018-06-20

Adams-Oliver syndrome (AOS) is a rare developmental disorder, characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Autosomal dominant forms of AOS are linked to mutations in ARHGAP31, DLL4, NOTCH1 or RBPJ, while DOCK6 and EOGT underlie autosomal recessive inheritance. Data on the frequency and distribution of mutations in large cohorts is currently limited. The purpose of this study was therefore to comprehensively examine the genetic architecture of AOS in an extensive cohort. Molecular diagnostic screening of 194 AOS/ACC/TTLD probands/families was conducted using next-generation and/or capillary sequencing analyses. In total, we identified 63 (likely) pathogenic mutations, comprising 56 distinct and 22 novel mutations, providing a molecular diagnosis in 30% of patients. Taken together with previous reports, these findings bring the total number of reported disease variants to 63, with a diagnostic yield of 36% in familial cases. NOTCH1 is the major contributor, underlying 10% of AOS/ACC/TTLD cases, with DLL4 (6%), DOCK6 (6%), ARHGAP31 (3%), EOGT (3%), and RBPJ (2%) representing additional causality in this cohort. We confirm the relevance of genetic screening across the AOS/ACC/TTLD spectrum, highlighting preliminary but important genotype-phenotype correlations. This cohort offers potential for further gene identification to address missing heritability. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Exposure matrix development for the Libby cohort.

PubMed

Noonan, C W

2006-11-01

The Libby, MT, cohort includes current and former residents with potential historical exposure to asbestos-contaminated vermiculite. This cohort includes individuals with a broad range of exposure experiences and work histories. While both occupational and nonoccupational exposure pathways were found to be relevant in recent investigations of health effects among this cohort, there has not been a comprehensive approach to characterizing these varied exposure pathways. Any approach toward assessing historical exposures among this population must account for three general categories: (1) occupational exposures, (2) residential exposures, and (3) exposures related to a variety of nonoccupational activities thought to be associated with vermiculite/asbestos exposure in this community. First, a job exposure matrix is commonly used in occupational epidemiology to assess historical worker exposures, allowing for the incorporation of numerous occupational categories and weighting factors applied to specific jobs for different time periods. Second, residential exposures can best be quantified by integrating individuals' residential histories with data on environmental asbestos contamination in the community. Previous soil or sediment sampling as well as air modeling could inform estimates of time- and spatial-dependent exposure concentrations for a residential exposure matrix. Finally, exposure opportunities due to nonoccupational activities could be weighted by factors such as time, geography, environmental sampling, and an assessment of the relative importance for each pathway. These three matrices for occupational, residential, and activity exposure pathways could be combined or used separately to provide a more comprehensive and quantitative, or semiquantitative, assessment of individual exposure in future epidemiological studies of this cohort.

[Psychological features and cognitive styles of students entering medicine and other careers at the Pontificia Universidad Católica de Chile].

PubMed

Bitran, Marcela; Zúñiga, Denisse; Lafuente, Montserrat; Viviani, Paola; Mena, Beltrán

2004-07-01

The similarity between the psychological features of medical school freshmen of different cohorts suggests that Medicine attracts students with specific psychological types. However, it is also possible that medical students are similar to the students admitted to any other career with high admission requirements. To determine if medical school freshmen are different from those of Engineering, Architecture, Psychology and Journalism. The Spanish version of the Myers Briggs Psychological Type Indicator (MBTI) was applied to two cohorts of Medical School freshmen (90 students of the 2000 cohort and 91 students of the 2001 cohort) and to a sample of 669 freshmen from the careers of Engineering, Psychology, Architecture and Journalism. Students entering Medical School are similar to the students admitted to Engineering and different from those that entered Architecture, Psychology and Journalism in the Pontificia Universidad Católica de Chile in 2000 and 2001. Medicine attracts a larger proportion of concrete and practical students that have an objective and systematic approach to study and to life in general. Unlike Medicine, Psychology and Architecture attract more students that have a cognitive style characterized by an intuitive perception, and that face life with an open and flexible attitude. This study reveals that the psychological features of undergradutate students are associated to their career choice. These psychological variables, therefore, may be relevant to the students' vocational preferences and possibly to their future specialty choice.

Heterogeneous PSMA expression on circulating tumor cells - a potential basis for stratification and monitoring of PSMA-directed therapies in prostate cancer

PubMed Central

Gorges, Tobias M.; Riethdorf, Sabine; von Ahsen, Oliver; Nastały, Paulina; Röck, Katharina; Boede, Marcel; Peine, Sven; Kuske, Andra; Schmid, Elke; Kneip, Christoph; König, Frank; Rudolph, Marion; Pantel, Klaus

2016-01-01

The prostate specific membrane antigen (PSMA) is the only clinically validated marker for therapeutic decisions in prostate cancer (PC). Characterization of circulating tumor cells (CTCs) obtained from the peripheral blood of PC patients might provide an alternative to tissue biopsies called “liquid biopsy”. The aim of this study was to develop a reliable assay for the determination of PSMA on CTCs. PSMA expression was analyzed on tissue samples (cohort one, n = 75) and CTCs from metastatic PC patients (cohort two, n = 29). Specific signals for the expression of PSMA could be seen for different prostate cancer cell line cells (PC3, LaPC4, 22Rv1, and LNCaP) by Western blot, immunohistochemistry (IHC), immunocytochemistry (ICC), and FACS. PSMA expression was found to be significantly increased in patients with higher Gleason grade (p = 0.0011) and metastases in lymph nodes (p = 0.0000085) or bone (p = 0.0020) (cohort one). In cohort two, CTCs were detectable in 20 out of 29 samples (69 %, range from 1 - 1000 cells). Twelve out of 20 CTC-positive patients showed PSMA-positive CTCs (67 %, score 1+ to 3+). We found intra-patient heterogeneity regarding the PSMA status between CTCs and the corresponding primary tumors. The results of our study could help to address the question whether treatment decisions based on CTC PSMA profiling will lead to a measurable benefit in clinical outcome for prostate cancer patients in the near future. PMID:27145459

Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles.

PubMed

Tan, J H T; Hoh, S F; Win, M T M; Chan, Y H; Das, L; Arkachaisri, T

2015-08-01

Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterized by immune dysregulation affecting patients less than 18 years old. One-fifth of SLE cases are diagnosed during childhood. cSLE presents differently from adults and has a more severe and aggressive course. We describe the clinical and antibody profiles in our cSLE Singapore cohort. All cSLE patients who satisfied the 1997 American College of Rheumatology diagnostic criteria were captured in our lupus registry from January 2009 to January 2014. Data including demographic, cumulative clinical, serologic data, and damage indices were collected. Adjusted mean SLEDAI-2K (AMS) was used to summarize disease activity over multiple visits. Cluster analysis using non-hierarchical K-means procedure was performed on eight selected antibodies. The 64 patients (female:male ratio 5:1; Chinese 45.3%, Malay 28.1%, Indian 9.4%, and other races 17.2%) had a mean onset age of 11.5 years (range 2.1-16.7) and mean age at diagnosis was 11.9 years (range 2.6-18.0). Our study demonstrated differences in clinical manifestations for which hematologic involvement was the most common manifestation with less renal disease and uncommon neurologic manifestation as compared to other cSLE cohorts reported in our region. Antibody clusters were identified in our cohort but their clinical association/discrimination and outcome prediction required further validation study. Outcomes of our cohort in regard to disease activity after therapy and organ damages were comparable if not better to other cSLE cohorts elsewhere. Steroid-related damage, including symptomatic multifocal avascular necrosis and cataract, were not uncommon locally. Infection remains the major cause of death for the continent. Nevertheless, the five year survival rate of our cohort (98.4%) was high. © The Author(s) 2015.

Clinical and genetic characterization of a founder PKHD1 mutation in Afrikaners with ARPKD.

PubMed

Lambie, Lindsay; Amin, Rasheda; Essop, Fahmida; Cnaan, Avital; Krause, Amanda; Guay-Woodford, Lisa M

2015-02-01

Autosomal recessive polycystic kidney disease (ARPKD; MIM 263200) occurs in 1:20,000 live births. Disease expression is widely variable, with approximately 30 % of affected neonates dying perinatally, while others survive to adulthood. Mutations at the PKHD1 locus are responsible for all typical presentations. The objectives of this study were to define the clinical and genetic characteristics in a cohort of South African patients of Afrikaner origin, a population with a high prevalence of ARPKD. DNA from the cohort was analyzed for background haplotypes and the p.M627K mutation previously identified in two unrelated Afrikaner patients. The clinical phenotype of the homozygous group was characterized. Analysis of 36 Afrikaner families revealed that 27 patients, from 24 (67 %) families, were homozygous for the p.M627K substitution, occurring on a common haplotype. The clinical phenotype of the homozygous individuals was variable. Our data provide strong evidence that the p.M627K substitution is a founder mutation in the Afrikaner population and can be used for streamlined diagnostic testing for at-risk pregnancies. The observed clinical variability suggests that disease expression is modulated by other genetic loci or by gene-environment interactions.

Association study between Van der Woude Syndrome causative gene GRHL3 and nonsyndromic cleft lip with or without cleft palate in a Chinese cohort.

PubMed

Wang, Yirui; Sun, Yimin; Huang, Yongqing; Pan, Yongchu; Jia, Zhonglin; Ma, Lijuan; Ma, Lan; Lan, Feifei; Zhou, Yuxi; Shi, Jiayu; Yang, Xiong; Zhang, Lei; Jiang, Hongbing; Jiang, Min; Yin, Aihua; Cheng, Jing; Wang, Lin; Yang, Yinxue; Shi, Bing

2016-08-15

Cleft lip with or without cleft palate (CL/P) is one of the most common birth defects worldwide and is characterized by abnormalities of the orofacial structure. Syndromic CL/P is mainly caused by Mendelian disorders such as Van der Woude Syndrome (VWS). However, >70% of CL/P cases are nonsyndromic, characterized by isolated orofacial cleft without any known syndrome. The etiology of nonsyndromic CL/P (NSCL/P) remains elusive, but it has been suggested that causative genes of syndromic CL/P might also contribute to NSCL/P. As such, the VWS causative gene IRF6 has been extensively studied in NSCL/P. Recently, GRHL3 was identified as another VWS causative gene. Thus, it may be a novel candidate gene for NSCL/P. In the present study, we genotyped 10 tag SNPs covering GRHL3 and performed association analysis with NSCL/P in 504 cases and 455 healthy controls. Our preliminary results identified rs10903078, rs4638975, and a haplotype rs10903078-rs6659209 of GRHL3 that exceeded the significance threshold (p<0.05), though none survived Bonferroni correction for multiple comparisons. As the first study between GRHL3 and NSCL/P, the contribution of this gene to NSCL/P etiology should be interpreted with caution based on existing evidence. Further, the robustness of association between GRHL3 and NSCL/P should be further validated in expanded cohorts. Copyright © 2016. Published by Elsevier B.V.

Personality traits of pharmacy and medical students throughout their course of studies

PubMed Central

Cordina, Maria; Lauri, Mary-Anne; Buttigieg, Raphael; LAURI, Josef

2015-01-01

Background: Pharmacists and medical doctors are two professional groups that very often receive their education and practice in the same environment. However, their approach to patient care and collaboration tends to be different and this may lead to both frustration and conflict which may adversely affect patient care. Personality has been identified as a psychological issue that could contribute to conflict in a work situation. Objective: To study the personality traits of a cohort of students studying pharmacy and medicine at the University of Malta in their first and final year. Methods: The Gordon Personal Profile – Inventory was administered to a cohort of pharmacy and medical students in their first year and once again administered to the same cohort who completed their course of study in their final year. Basic demographic data was also collected. Results: In first year the most pronounced traits for both student groups were those of Emotional Stability and Personal Relations. Over a period of five years, there were shifts in personality traits. In their final year pharmacy students were characterized by high scores for Cautiousness and Personal Relations while medical students exhibited medium scores in Cautiousness and Emotional Stability. Conclusion: The changes in personality traits over the duration of the course were not radical changes but rather that of traits becoming more pronounced. PMID:26759618

Clinical spectrum of primary hyperoxaluria type 1: Experience of a tertiary center

PubMed Central

Soliman, Neveen A.; Nabhan, Marwa M.; Abdelrahman, Safaa M.; Abdelaziz, Hanan; Helmy, Rasha; Ghanim, Khaled; Bazaraa, Hafez M.; Badr, Ahmed M.; Tolba, Omar A.; Kotb, Magd A.; Eweeda, Khaled M.; Fayez, Alaa

2018-01-01

Background and aim Primary hyperoxalurias are rare inborn errors of metabolism resulting in increased endogenous production of oxalate that leads to excessive urinary oxalate excretion. Diagnosis of primary hyperoxaluria type 1 (PH1) is a challenging issue and depends on diverse diagnostic tools including biochemical analysis of urine, stone analysis, renal biopsy, genetic studies and in some cases liver biopsy for enzyme assay. We characterized the clinical presentation as well as renal and extrarenal phenotypes in PH1 patients. Methods This descriptive cohort study included patients with presumable PH1 presenting with nephrolithiasis and/or nephrocalcinosis (NC). Precise clinical characterization of renal phenotype as well as systemic involvement is reported. AGXT mutational analysis was performed to confirm the diagnosis of PH1. Results The study cohort included 26 patients with presumable PH1 with male to female ratio of 1.4:1. The median age at time of diagnosis was 6 years, nevertheless the median age at initial symptoms was 3 years. Thirteen patients (50%) were diagnosed before the age of 5 years. Two patients had no symptoms and were diagnosed while screening siblings of index patients. Seventeen patients (65.4%) had reached end-stage renal disease (ESRD): 6/17 (35.3%) during infancy, 4/17 (23.5%) in early childhood and 7/17 (41.29%) in late childhood. Two patients (7.7%) had clinically manifest extra renal (retina, heart, bone, soft tissue) involvement. Mutational analysis of AGXT gene confirmed the diagnosis of PH1 in 15 out of 19 patients (79%) where analysis had been performed. Fifty percent of patients with maintained renal functions had projected 10 years renal survival. Conclusion PH1 is a heterogeneous disease with wide spectrum of clinical, imaging and functional presentation. More than two-thirds of patients presented prior to the age of 5 years; half of them with the stormy course of infantile PH1. ESRD was the commonest presenting manifestation in two-thirds of our cohort. PMID:28161266

Rubinstein-Taybi 2 associated to novel EP300 mutations: deepening the clinical and genetic spectrum.

PubMed

López, María; García-Oguiza, Alberto; Armstrong, Judith; García-Cobaleda, Inmaculada; García-Miñaur, Sixto; Santos-Simarro, Fernando; Seidel, Verónica; Domínguez-Garrido, Elena

2018-03-05

Rubinstein-Taybi syndrome (RSTS) is a rare autosomal dominant neurodevelopmental disorder characterized by broad thumbs and halluces. RSTS is caused by mutations in CREBBP and in EP300 genes in 50-60% and 8%, respectively. Up to now, 76 RSTS-EP300 patients have been described. We present the clinical and molecular characterization of a cohort of RSTS patients carrying EP300 mutations. Patients were selected from a cohort of 72 individuals suspected of RSTS after being negative in CREBBP study. MLPA and panel-based NGS EP300 were performed. Eight patients were found to carry EP300 mutations. Phenotypic characteristics included: intellectual disability (generally mild), postnatal growth retardation, infant feeding problems, psychomotor and language delay and typical facial dysmorphisms (microcephaly, downslanting palpebral fissures, columella below the alae nasi, and prominent nose). Broad thumbs and/or halluces were common, but angulated thumbs were only found in two patients. We identified across the gene novel mutations, including large deletion, frameshift mutations, nonsense, missense and splicing alterations, confirming de novo origin in all but one (the mother, possibly underdiagnosed, has short and broad thumbs and had learning difficulties). The clinical evaluation of our patients corroborates that clinical features in EP300 are less marked than in CREBBP patients although it is difficult to establish a genotype-phenotype correlation although. It is remarkable that these findings are observed in a RSTS-diagnosed cohort; some patients harbouring EP300 mutations could present a different phenotype. Broadening the knowledge about EP300-RSTS phenotype may contribute to improve the management of patients and the counselling to the families.

A Risk Prediction Score for Kidney Failure or Mortality in Rhabdomyolysis

PubMed Central

McMahon, Gearoid M.; Zeng, Xiaoxi; Waikar, Sushrut S.

2016-01-01

IMPORTANCE Rhabdomyolysis ranges in severity from asymptomatic elevations in creatine phosphokinase levels to a life-threatening disorder characterized by severe acute kidney injury requiring hemodialysis or continuous renal replacement therapy (RRT). OBJECTIVE To develop a risk prediction tool to identify patients at greatest risk of RRT or in-hospital mortality. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study of 2371 patients admitted between January 1, 2000, and March 31, 2011, to 2 large teaching hospitals in Boston, Massachusetts, with creatine phosphokinase levels in excess of 5000 U/L within 3 days of admission. The derivation cohort consisted of 1397 patients from Massachusetts General Hospital, and the validation cohort comprised 974 patients from Brigham and Women’s Hospital. MAIN OUTCOMES AND MEASURES The composite of RRT or in-hospital mortality. RESULTS The causes and outcomes of rhabdomyolysis were similar between the derivation and validation cohorts. In total, the composite outcome occurred in 19.0% of patients (8.0% required RRT and 14.1% died during hospitalization). The highest rates of the composite outcome were from compartment syndrome (41.2%), sepsis (39.3%), and following cardiac arrest (58.5%). The lowest rates were from myositis (1.7%), exercise (3.2%), and seizures (6.0%). The independent predictors of the composite outcome were age, female sex, cause of rhabdomyolysis, and values of initial creatinine, creatine phosphokinase, phosphate, calcium, and bicarbonate. We developed a risk-prediction score from these variables in the derivation cohort and subsequently applied it in the validation cohort. The C statistic for the prediction model was 0.82 (95% CI, 0.80–0.85) in the derivation cohort and 0.83 (0.80–0.86) in the validation cohort. The Hosmer-Lemeshow P values were .14 and .28, respectively. In the validation cohort, among the patients with the lowest risk score (<5), 2.3% died or needed RRT. Among the patients with the highest risk score (>10), 61.2% died or needed RRT. CONCLUSIONS AND RELEVANCE Outcomes from rhabdomyolysis vary widely depending on the clinical context. The risk of RRT or in-hospital mortality in patients with rhabdomyolysis can be estimated using commonly available demographic, clinical, and laboratory variables on admission. PMID:24000014

PNPLA3 148M Carriers with Inflammatory Bowel Diseases Have Higher Susceptibility to Hepatic Steatosis and Higher Liver Enzymes.

PubMed

Mancina, Rosellina Margherita; Spagnuolo, Rocco; Milano, Marta; Brogneri, Simona; Morrone, Attilio; Cosco, Cristina; Lazzaro, Veronica; Russo, Cristina; Ferro, Yvelise; Pingitore, Piero; Pujia, Arturo; Montalcini, Tiziana; Doldo, Patrizia; Garieri, Pietro; Piodi, Luca; Caprioli, Flavio; Valenti, Luca; Romeo, Stefano

2016-01-01

Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract and encompass Crohn's disease and ulcerative colitis. IBD are often associated with extraintestinal manifestations affecting multiple organs including the liver. Increased levels of serum aminotransferases, possibly related to nonalcoholic fatty liver disease, constitute one of the most frequently described IBD-related liver diseases. The PNPLA3 I148M substitution is a major common genetic determinant of hepatic fat content and progression to chronic liver disease. The aim of this study was to investigate whether carriers of PNPLA3 148M allele with IBD have higher risk of liver steatosis and increase in transaminases levels. The PNPLA3 I148M (rs738409) genotype was performed by Taqman assays in 158 individuals from Southern Italy (namely, Catanzaro cohort) and in 207 individuals from Northern Italy (namely, Milan cohort) with a definite diagnosis of IBD. Demographic and clinical data and also alanine transaminase levels were collected for both cohorts. The Catanzaro cohort underwent liver evaluation by sonography and liver stiffness and controlled attenuation parameter measurements by transient elastography. Here, we show for the first time that carriers of the PNPLA3 148M allele with IBD have a greater risk of hepatic steatosis (odds ratio, 2.9, and confidence interval, 1.1-7.8), higher controlled attenuation parameter values (P = 0.029), and increased circulating alanine transaminase (P = 0.035) in the Catanzaro cohort. We further confirm the higher alanine transaminase levels in the Milan cohort (P < 0.001). Our results show that PNPLA3 148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage.

Biomarkers of Rheumatoid Arthritis–Associated Interstitial Lung Disease

PubMed Central

Chen, Juan; Doyle, Tracy J.; Liu, Yongliang; Aggarwal, Rohit; Wang, Xiaoping; Shi, Yonghong; Ge, Sheng Xiang; Huang, Heqing; Lin, Qingyan; Liu, Wen; Cai, Yongjin; Koontz, Diane; Fuhrman, Carl R.; Golzarri, Maria F.; Liu, Yushi; Hatabu, Hiroto; Nishino, Mizuki; Araki, Tetsuro; Dellaripa, Paul F.; Oddis, Chester V.; Rosas, Ivan O.; Ascherman, Dana P.

2015-01-01

Objective Interstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA-associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication. Methods Patients with RA who were enrolled in a well-characterized Chinese identification cohort or a US replication cohort were subclassified as having RA–no ILD, RA–mild ILD, or RA–advanced ILD, based on high-resolution computed tomography scans of the chest. Multiplex enzyme-linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute-phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA-ILD and biomarkers of interest. Results MMP-7 and interferon-γ–inducible protein 10 (IP-10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA-ILD in 133 RA patients comprising the Chinese identification cohort (50 RA–no ILD, 41 RA-ILD, 42 RA–indeterminate ILD). The findings were confirmed by standard solid-phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RA–no ILD, 49 RA-ILD, 15 RA–indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses. Conclusion Levels of MMP-7 and IP-10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication. PMID:25302945

Endogenous estrogens and breast cancer risk: the case for prospective cohort studies.

PubMed Central

Toniolo, P G

1997-01-01

It is generally agreed that estrogens, and possibly androgens, are important in the etiology of breast cancer, but no consensus exists as to the precise estrogenic or androgenic environment that characterizes risk, or the exogenous factors that influence the hormonal milieu. Nearly all the epidemiological studies conducted in the 1970s and 1980s were hospital-based case-control studies in which specimen sampling was performed well after the clinical appearance of the disease. Early prospective cohort studies also had limitations in their small sample sizes or short follow-up periods. However, more recent case-control studies nested within large cohorts, such as the New York University Women's Health Study and the Ormoni e Dieta nell'Eziologia dei Tumori study in Italy, are generating new data indicating that increased levels of estrone, estradiol and bioavailable estradiol, as well as their androgenic precursors, may be associated with a 4- to 6-fold increase in the risk of postmenopausal breast cancer. Further new evidence, which complements and expands the observations from the latter studies, shows that women with the thickest bone density, which may be a surrogate for cumulated exposure to hormones, experience severalfold increased risk of subsequent breast cancer as compared to women with thin bones. These data suggests that endogenous sex hormones are a key factor in the etiology of postmenopausal breast cancer. New prospective cohort studies should be conducted to examine the role of endogenous sex hormones in blood and urine samples obtained early in the natural history of breast cancer jointly with an assessment of bone density and of other important risk factors, such as mammographic density, physical activity, body weight, and markers of individual susceptibility, which may confer increased risk through an effect on the metabolism of endogenous hormones or through specific metabolic responses to Western lifestyle and diet. PMID:9168000

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.

Expanding the Phenotypic and Genotypic Landscape of Autoimmune Polyendocrine Syndrome Type 1.

PubMed

Orlova, Elizaveta M; Sozaeva, Leila S; Kareva, Maria A; Oftedal, Bergithe E; Wolff, Anette S B; Breivik, Lars; Zakharova, Ekaterina Y; Ivanova, Olga N; Kämpe, Olle; Dedov, Ivan I; Knappskog, Per M; Peterkova, Valentina A; Husebye, Eystein S

2017-09-01

Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene and characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. Comprehensive characterizations of large patient cohorts are rare. To perform an extensive clinical, immunological, and genetic characterization of a large nationwide Russian APS-1 cohort. Clinical components were mapped by systematic investigations, sera were screened for autoantibodies associated with APS-1, and AIRE mutations were characterized by Sanger sequencing. We identified 112 patients with APS-1, which is, to the best of our knowledge, the largest cohort described to date. Careful phenotyping revealed several additional and uncommon phenotypes such as cerebellar ataxia with pseudotumor, ptosis, and retinitis pigmentosa. Neutralizing autoantibodies to interferon-ω were found in all patients except for one. The major Finnish mutation c.769C>T (p.R257*) was the most frequent and was present in 72% of the alleles. Altogether, 19 different mutations were found, of which 9 were unknown: c.38T>C (p.L13P), c.173C>T (p.A58V), c.280C>T (p.Q94*), c.554C>G (p.S185*), c.661A>T (p.K221*), c.821del (p.Gly274Afs*104), c.1195G>C (p.A399P), c.1302C>A (p.C434*), and c.1497del (p.A500Pfs*21). The spectrum of phenotypes and AIRE mutation in APS-1 has been expanded. The Finnish major mutation is the most common mutation in Russia and is almost as common as in Finland. Assay of interferon antibodies is a robust screening tool for APS-1. Copyright © 2017 Endocrine Society

SH3-domain binding protein 1 in the tumor microenvironment promotes hepatocellular carcinoma metastasis through WAVE2 pathway

PubMed Central

Tao, Yiming; Hu, Kuan; Tan, Fengbo; Zhang, Sai; Zhou, Ming; Luo, Jia; Wang, Zhiming

2016-01-01

SH3-domain binding protein-1 (SH3BP1) specifically inactivating Rac1 and its target WAVE2 is required for cell motility. The present study shows SH3BP1 expression patterns in human HCC tissues and cell lines were examined. The regulation of SH3BP1 on HCC cell migration and invasion related to Rac1-WAVE2 signaling was characterized using in vitro and in vivo models. SH3BP1 overexpressed in HCC tissues and highly metastatic HCC cells was significantly associated vascular invasion (VI). SH3BP1 promoted VEGF secretion via Rac1-WAVE2 signaling, so as to exert an augmentation on cell invasion and microvessel formation. In three study cohorts with a total of 516 HCC patients, high SH3BP1 expression combined with high microvessel density (MVD) was confirmed as a powerful independent predictor of HCC prognosis in both training cohorts and validation cohort. Being an important angiogenic factor of HCC through Rac1-WAVE2 signaling, SH3BP1 promotes tumor invasion and microvessel formation contributing to HCC metastasis and recurrence. SH3BP1 is a novel WAVE2 regulator, a prognostic marker and a potential therapeutic target of HCC. PMID:26933917

SH3-domain binding protein 1 in the tumor microenvironment promotes hepatocellular carcinoma metastasis through WAVE2 pathway.

PubMed

Tao, Yiming; Hu, Kuan; Tan, Fengbo; Zhang, Sai; Zhou, Ming; Luo, Jia; Wang, Zhiming

2016-04-05

SH3-domain binding protein-1 (SH3BP1) specifically inactivating Rac1 and its target WAVE2 is required for cell motility. The present study shows SH3BP1 expression patterns in human HCC tissues and cell lines were examined. The regulation of SH3BP1 on HCC cell migration and invasion related to Rac1-WAVE2 signaling was characterized using in vitro and in vivo models. SH3BP1 overexpressed in HCC tissues and highly metastatic HCC cells was significantly associated vascular invasion (VI). SH3BP1 promoted VEGF secretion via Rac1-WAVE2 signaling, so as to exert an augmentation on cell invasion and microvessel formation. In three study cohorts with a total of 516 HCC patients, high SH3BP1 expression combined with high microvessel density (MVD) was confirmed as a powerful independent predictor of HCC prognosis in both training cohorts and validation cohort. Being an important angiogenic factor of HCC through Rac1-WAVE2 signaling, SH3BP1 promotes tumor invasion and microvessel formation contributing to HCC metastasis and recurrence. SH3BP1 is a novel WAVE2 regulator, a prognostic marker and a potential therapeutic target of HCC.

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.

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

PubMed

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

2016-02-01

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

Pulmonary artery enlargement and cystic fibrosis pulmonary exacerbations: a cohort study

PubMed Central

Wells, J. Michael; Farris, Roopan F.; Gosdin, Taylor A.; Dransfield, Mark T.; Wood, Michelle E.; Bell, Scott C.; Rowe, Steven M.

2017-01-01

Background Acute pulmonary exacerbations are associated with progressive lung function decline and increased mortality in cystic fibrosis (CF). The role of pulmonary vascular disease in pulmonary exacerbations is unknown. We investigated the association between pulmonary artery enlargement (PA:A>1), a marker of pulmonary vascular disease, and exacerbations. Methods We analyzed clinical, computed tomography (CT), and prospective exacerbation data in a derivation cohort of 74 adult CF patients, measuring the PA:A at the level of the PA bifurcation. We then replicated our findings in a validation cohort of 190 adult CF patients. Patients were separated into groups based on the presence or absence of a PA:A>1 and were followed for 1-year in the derivation cohort and 2-years in the validation cohort. The primary endpoint was developing ≥1 acute pulmonary exacerbation during follow-up. Linear and logistic regression models were used to determine associations between clinical factors, the PA:A ratio, and pulmonary exacerbations. We used Cox regression to determine time to first exacerbation in the validation cohort. Findings We found that PA:A>1 was present in n=37/74 (50%) of the derivation and n=89/190 (47%) of the validation cohort. In the derivation cohort, n=50/74 (68%) had ≥1 exacerbation at 1 year and n=133/190 (70%) in the validation cohort had ≥1 exacerbation after 2 years. PA:A>1 was associated with younger age in both cohorts and with elevated sweat chloride (100.5±10.9 versus 90.4±19.9mmol/L, difference between groups 10.1mmol/L [95%CI 2.5–17.7], P=0.017) in the derivation group. PA:A>1 was associated with exacerbations in the derivation (OR 3.49, 95%CI 1.18–10.3, P=0.023) and validation (OR 2.41, 95%CI 1.06–5.52, P=0.037) cohorts when adjusted for confounders. Time to first exacerbation was shorter in PA:A>1 versus PA:A<1 [HR 1.66 (95%CI 1.18–2.34), P=0.004] in unadjusted analysis, but not when adjusted for sex, BMI, prior exacerbation, positive Pseudomonas status, and FEV1/FVC [HR 1.14 (95%CI 0.80–1.62), P=0.82]). Interpretation PA enlargement is prevalent in adult CF patients and is associated with acute pulmonary exacerbation risk in two well-characterized cohorts. PA:A may be a predictive marker in CF. PMID:27298019

Novel MRI-derived quantitative biomarker for cardiac function applied to classifying ischemic cardiomyopathy within a Bayesian rule learning framework

NASA Astrophysics Data System (ADS)

Menon, Prahlad G.; Morris, Lailonny; Staines, Mara; Lima, Joao; Lee, Daniel C.; Gopalakrishnan, Vanathi

2014-03-01

Characterization of regional left ventricular (LV) function may have application in prognosticating timely response and informing choice therapy in patients with ischemic cardiomyopathy. The purpose of this study is to characterize LV function through a systematic analysis of 4D (3D + time) endocardial motion over the cardiac cycle in an effort to define objective, clinically useful metrics of pathological remodeling and declining cardiac performance, using standard cardiac MRI data for two distinct patient cohorts accessed from CardiacAtlas.org: a) MESA - a cohort of asymptomatic patients; and b) DETERMINE - a cohort of symptomatic patients with a history of ischemic heart disease (IHD) or myocardial infarction. The LV endocardium was segmented and a signed phase-to-phase Hausdorff distance (HD) was computed at 3D uniformly spaced points tracked on segmented endocardial surface contours, over the cardiac cycle. An LV-averaged index of phase-to-phase endocardial displacement (P2PD) time-histories was computed at each tracked point, using the HD computed between consecutive cardiac phases. Average and standard deviation in P2PD over the cardiac cycle was used to prepare characteristic curves for the asymptomatic and IHD cohort. A novel biomarker of RMS error between mean patient-specific characteristic P2PD over the cardiac cycle for each individual patient and the cumulative P2PD characteristic of a cohort of asymptomatic patients was established as the RMS-P2PD marker. The novel RMS-P2PD marker was tested as a cardiac function based feature for automatic patient classification using a Bayesian Rule Learning (BRL) framework. The RMS-P2PD biomarker indices were significantly different for the symptomatic patient and asymptomatic control cohorts (p<0.001). BRL accurately classified 83.8% of patients correctly from the patient and control populations, with leave-one-out cross validation, using standard indices of LV ejection fraction (LV-EF) and LV end-systolic volume index (LV-ESVI). This improved to 91.9% with inclusion of the RMS-P2PD biomarker and was congruent with improvements in both sensitivity for classifying patients and specificity for identifying asymptomatic controls from 82.6% up to 95.7%. RMS-P2PD, when contrasted against a collective normal reference, is a promising biomarker to investigate further in its utility for identifying quantitative signs of pathological endocardial function which may boost standard image makers as precursors of declining cardiac performance.

A cohort study of psychosocial work stressors on work ability among Brazilian hospital workers.

PubMed

Martinez, Maria Carmen; do Rosário Dias de Oliveira Latorre, Maria; Fischer, Frida Marina

2015-07-01

Hospital work is characterized by stressors that can influence work ability. The present study aims to assess the association between psychosocial work stressors and changes in work ability in a group of Brazilian hospital employees. From 1,022 workers included in a 3-year cohort started in 2009, 423 (41.4%) returned the applied questionnaires in 2012. Changes in work ability were considered as the dependent variable and the investigated psychosocial work stressors as independent variables. Logistic regression models adjusted for potential con-founders (demographic, occupational features, social support, overcommitment, and situations liable to cause pain/injury). High levels of exposure to psychosocial work stressors were significantly associated with decreased work ability: job strain (OR = 2.81), effort-reward imbalance (OR = 3.21). Strategies to reduce psychosocial work stressors should be considered to maintain hospital employees' work ability. Such strategies have implications for institutional and social policies and might be included in quality management programs. © 2015 Wiley Periodicals, Inc.

Investigating the psychological impact of bank robbery: a cohort study.

PubMed

Hansen, Maj; Armour, Cherie; Shevlin, Mark; Elklit, Ask

2014-06-01

Despite numerous annual bank robberies worldwide, research in the psychological sequelae of bank robberies is sparse and characterized by several limitations. To overcome these limitations we investigated the psychological impact of bank robbery in a cohort study by comparing general levels of traumatization and somatization in employees never exposed to robbery and employees exposed to robbery at different degrees and time-points, while controlling for selected risk factors of posttraumatic distress. Multivariate regression analyses showed that only the acute directly exposed robbery group which had a significantly higher score on general traumatization and somatization compared to the control group whilst controlling for other factors. In conclusion, bank robbery exposure appears to be especially associated with psychological distress in the acute phase and in victims present during the robbery. After the acute phase, other factors appear more important in predicting general traumatization and somatization in bank employees compared to exposure to robbery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Disk displacement, eccentric condylar position, osteoarthrosis - misnomers for variations of normality? Results and interpretations from an MRI study in two age cohorts.

PubMed

Türp, Jens C; Schlenker, Anna; Schröder, Johannes; Essig, Marco; Schmitter, Marc

2016-11-17

Clinical decision-making and prognostic statements in individuals with manifest or suspected temporomandibular disorders (TMDs) may involve assessment of (a) the position of articular disc relative to the mandibular condyle, (b) the location of the condyle relative to the temporal joint surfaces, and (c) the depth of the glenoid fossa of the temporomandibular joints (TMJs). The aim of this study was twofold: (1) Determination of the prevalence of these variables in two representative population-based birth cohorts. (2) Reinterpretation of the clinical significance of the findings. From existing magnetic resonance imaging (MRI) scans of the TMJs that had been taken in 2005 and 2006 from 72 subjects born between 1930 and 1932 and between 1950 and 1952, respectively, the condylar position at closed jaw was calculated as percentage displacement of the condyle from absolute centricity. By using the criteria introduced by Orsini et al. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 86:489-97, 1998), a textbook-like disc position at closed jaw was distinguished from an anterior location. TMJ morphology of the temporal joint surfaces was assessed at open jaw by measuring the depth of the glenoid fossa, using the method proposed by Muto et al. (J Oral Maxillofac Surg 52:1269-72, 1994). Frequency distributions were recorded for the condylar and disc positions at closed jaw. Student's t-test with independent samples was used as test of significance to detect differences of condylar positions between the age cohorts (1930 vs. 1950) and the sexes. The significance levels were set at 5%. First, the results from the measurement of the age cohorts were compared without differentiation of sexes, i.e., age cohort 1930-1932 versus age cohort 1950-1952. Subsequently, the age cohorts were compared by sex, i.e., men in cohort 1930-1932 versus men in cohort 1950-1952, and women in cohort 1930-1932 women men in cohort 1950-1952. In both cohorts, condylar position was characterized by great variability. About 50% of the condyles were located centrically, while the other half was either in an anterior or in a posterior position. In both female cohorts, a posterior position predominated, whereas a centric position prevailed among men. Around 75% of the discs were positioned textbook-like, while the remaining forth was located anteriorly. Age had no statistically significant influence on condylar or on disc position. Conversely, comparison between the age groups revealed a statistically significant decrease of the depth of the glenoid fossa in both older cohorts. This age-dependent changes may be interpreted as flattening of the temporal joint surfaces. We call for a re-interpretation of imaging findings because they may insinuate pathology which usually is not present. Instead, anterior or posterior positions of the mandibular condyle as well as an anterior location of the articular disc should be construed as a variation of normalcy. Likewise, flattening of articular surfaces of the TMJs may be considered as normal adaptive responses to increased loading, rather than pathological degenerative changes. Not applicable.

Comparison of motor diagnoses by Chicago Classification versions 2.0 and 3.0 on esophageal high-resolution manometry.

PubMed

Patel, A; Cassell, B; Sainani, N; Wang, D; Shahid, B; Bennett, M; Mirza, F A; Munigala, S; Gyawali, C P

2017-07-01

The Chicago Classification (CC) uses high-resolution manometry (HRM) software tools to designate esophageal motor diagnoses. We evaluated changes in diagnostic designations between two CC versions, and determined motor patterns not identified by either version. In this observational cohort study of consecutive patients undergoing esophageal HRM over a 6-year period, proportions meeting CC 2.0 and 3.0 criteria were segregated into esophageal outflow obstruction, hypermotility, and hypomotility disorders. Contraction wave abnormalities (CWA), and 'normal' cohorts were recorded. Symptom burden was characterized using dominant symptom intensity and global symptom severity. Motor diagnoses, presenting symptoms, and symptom burden were compared between CC 2.0 and 3.0, and in cohorts not meeting CC diagnoses. Of 2569 eligible studies, 49.9% met CC 2.0 criteria, but only 40.3% met CC 3.0 criteria (P<.0001). Between CC 2.0 and 3.0, 82.8% of diagnoses were concordant. Discordance resulted from decreasing proportions of hypermotility (4.4%) and hypomotility (9.0%) disorders, and increase in 'normal' designations (13.0%); esophageal outflow obstruction showed the least variation between CC versions. Symptom burden was higher with CC 3.0 diagnoses (P≤.005) but not with CC 2.0 diagnoses (P≥.1). Within 'normal' cohorts for both CC versions, CWA were associated with higher likelihood of esophageal symptoms, especially dysphagia, regurgitation, and heartburn, compared to truly normal studies (P≤.02 for each comparison). Despite lower sensitivity, CC 3.0 identifies esophageal motor disorders with higher symptom burden compared to CC 2.0. CWA, which are associated with both transit and perceptive symptoms, are not well identified by either version. © 2017 John Wiley & Sons Ltd.

Hyperthyroidism and Risk for Bipolar Disorders: A Nationwide Population-Based Study

PubMed Central

Hu, Yu-Wen; Chen, Mu-Hong; Tsai, Chia-Fen; Chiang, Huey-Ling; Yeh, Chiu-Mei; Wang, Wei-Shu; Chen, Pan-Ming; Hu, Tsung-Ming; Chen, Tzeng-Ji; Su, Tung-Ping; Liu, Chia-Jen

2013-01-01

Background Thyroid disorders have long been associated with psychiatric illness, often with symptoms suggestive of mood disorders. The most common clinical features associated with hyperthyroidism are anxiety and depression. The risk of bipolar disorders, especially bipolar mania, among patients with thyroid disorders has not been well characterized. Objective We explored the relationship of hyperthyroidism and the subsequent development of bipolar disorders, and examined the risk factors for bipolar disorders in patients with hyperthyroidism. Methods We identified patients who were diagnosed with hyperthyroidism between 2000 and 2010 in the Taiwan National Health Insurance Research Database. A comparison cohort without hyperthyroidism was matched based on age, sex, and comorbidities. The occurrence of bipolar disorders was evaluated in both cohorts based on diagnosis and the use of mood stabilizer drugs. Results The hyperthyroidism cohort consisted of 21, 574 patients, and the comparison cohort consisted of 21, 574 matched control patients without hyperthyroidism. The incidence of bipolar disorders (incidence rate ratio [IRR], 2.31, 95% CI 1.80–2.99, P<.001) was higher for the hyperthyroidism patients than the control patients. Multivariate, matched regression models showed that women (HR 2.02, 95% CI 1.34–3.05, P = .001), patients with alcohol use disorders (HR 3.03, 95% CI 1.58–5.79, P = .001), and those with asthma (HR 1.70, 95% CI 1.18–2.43, P = .004) were independent risk factors for the development of bipolar disorders in hyperthyroidism patients. Conclusions Although a possibility that the diagnosis of bipolar disorders in this study actually includes "bipolar disorders due to hyperthyroidism" cannot be excluded, this study suggests that hyperthyroidism may increase the risk of developing bipolar disorders. PMID:24023669

The BioFIND study: Characteristics of a clinically typical Parkinson's disease biomarker cohort

PubMed Central

Goldman, Jennifer G.; Alcalay, Roy N.; Xie, Tao; Tuite, Paul; Henchcliffe, Claire; Hogarth, Penelope; Amara, Amy W.; Frank, Samuel; Rudolph, Alice; Casaceli, Cynthia; Andrews, Howard; Gwinn, Katrina; Sutherland, Margaret; Kopil, Catherine; Vincent, Lona; Frasier, Mark

2016-01-01

ABSTRACT Background Identifying PD‐specific biomarkers in biofluids will greatly aid in diagnosis, monitoring progression, and therapeutic interventions. PD biomarkers have been limited by poor discriminatory power, partly driven by heterogeneity of the disease, variability of collection protocols, and focus on de novo, unmedicated patients. Thus, a platform for biomarker discovery and validation in well‐characterized, clinically typical, moderate to advanced PD cohorts is critically needed. Methods BioFIND (Fox Investigation for New Discovery of Biomarkers in Parkinson's Disease) is a cross‐sectional, multicenter biomarker study that established a repository of clinical data, blood, DNA, RNA, CSF, saliva, and urine samples from 118 moderate to advanced PD and 88 healthy control subjects. Inclusion criteria were designed to maximize diagnostic specificity by selecting participants with clinically typical PD symptoms, and clinical data and biospecimen collection utilized standardized procedures to minimize variability across sites. Results We present the study methodology and data on the cohort's clinical characteristics. Motor scores and biospecimen samples including plasma are available for practically defined off and on states and thus enable testing the effects of PD medications on biomarkers. Other biospecimens are available from off state PD assessments and from controls. Conclusion Our cohort provides a valuable resource for biomarker discovery and validation in PD. Clinical data and biospecimens, available through The Michael J. Fox Foundation for Parkinson's Research and the National Institute of Neurological Disorders and Stroke, can serve as a platform for discovering biomarkers in clinically typical PD and comparisons across PD's broad and heterogeneous spectrum. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society PMID:27113479

Hyperthyroidism and risk for bipolar disorders: a nationwide population-based study.

PubMed

Hu, Li-Yu; Shen, Cheng-Che; Hu, Yu-Wen; Chen, Mu-Hong; Tsai, Chia-Fen; Chiang, Huey-Ling; Yeh, Chiu-Mei; Wang, Wei-Shu; Chen, Pan-Ming; Hu, Tsung-Ming; Chen, Tzeng-Ji; Su, Tung-Ping; Liu, Chia-Jen

2013-01-01

Thyroid disorders have long been associated with psychiatric illness, often with symptoms suggestive of mood disorders. The most common clinical features associated with hyperthyroidism are anxiety and depression. The risk of bipolar disorders, especially bipolar mania, among patients with thyroid disorders has not been well characterized. We explored the relationship of hyperthyroidism and the subsequent development of bipolar disorders, and examined the risk factors for bipolar disorders in patients with hyperthyroidism. We identified patients who were diagnosed with hyperthyroidism between 2000 and 2010 in the Taiwan National Health Insurance Research Database. A comparison cohort without hyperthyroidism was matched based on age, sex, and comorbidities. The occurrence of bipolar disorders was evaluated in both cohorts based on diagnosis and the use of mood stabilizer drugs. The hyperthyroidism cohort consisted of 21, 574 patients, and the comparison cohort consisted of 21, 574 matched control patients without hyperthyroidism. The incidence of bipolar disorders (incidence rate ratio [IRR], 2.31, 95% CI 1.80-2.99, P<.001) was higher for the hyperthyroidism patients than the control patients. Multivariate, matched regression models showed that women (HR 2.02, 95% CI 1.34-3.05, P = .001), patients with alcohol use disorders (HR 3.03, 95% CI 1.58-5.79, P = .001), and those with asthma (HR 1.70, 95% CI 1.18-2.43, P = .004) were independent risk factors for the development of bipolar disorders in hyperthyroidism patients. Although a possibility that the diagnosis of bipolar disorders in this study actually includes "bipolar disorders due to hyperthyroidism" cannot be excluded, this study suggests that hyperthyroidism may increase the risk of developing bipolar disorders.

MODUL-a multicenter randomized clinical trial of biomarker-driven maintenance therapy following first-line standard induction treatment of metastatic colorectal cancer: an adaptable signal-seeking approach.

PubMed

Schmoll, Hans-Joachim; Arnold, Dirk; de Gramont, Aimery; Ducreux, Michel; Grothey, Axel; O'Dwyer, Peter J; Van Cutsem, Eric; Hermann, Frank; Bosanac, Ivan; Bendahmane, Belguendouz; Mancao, Christoph; Tabernero, Josep

2018-06-01

The old approach of one therapeutic for all patients with mCRC is evolving with a need to target specific molecular aberrations or cell-signalling pathways. Molecular screening approaches and new biomarkers are required to fully characterize tumours, identify patients most likely to benefit, and predict treatment response. MODUL is a signal-seeking trial with a design that is highly adaptable, permitting modification of different treatment cohorts and inclusion of further additional cohorts based on novel evidence on new compounds/combinations that emerge during the study. MODUL is ongoing and its adaptable nature permits timely and efficient recruitment of patients into the most appropriate cohort. Recruitment will take place over approximately 5 years in Europe, Asia, Africa, and South America. The design of MODUL with ongoing parallel/sequential treatment cohorts means that the overall size and duration of the trial can be modified/prolonged based on accumulation of new data. The early success of the current trial suggests that the design may provide definitive leads in a patient-friendly and relatively economical trial structure. Along with other biomarker-driven trials that are currently underway, it is hoped that MODUL will contribute to the continuing evolution of clinical trial design and permit a more 'tailored' approach to the treatment of patients with mCRC.

Efficacy and safety of growth hormone treatment in children with hypochondroplasia: comparison with an historical cohort.

PubMed

Pinto, Graziella; Cormier-Daire, Valérie; Le Merrer, Martine; Samara-Boustani, Dinane; Baujat, Geneviève; Fresneau, Laurence; Viaud, Magali; Souberbielle, Jean Claude; Pineau, Jean Claude; Polak, Michel

2014-01-01

Hypochondroplasia (HCH) is a skeletal dysplasia characterized by disproportionate short stature. The aims of the study are to evaluate efficacy and safety of recombinant human growth hormone (r-hGH) therapy in HCH children, when compared with a historical cohort of untreated HCH children. Nineteen HCH patients with an initial height standard deviation score (SDS) ≤-2 and a mean age of 9.3 ± 3.1 years were treated with a mean r-hGH dose of 0.053 mg/kg/day over 3 years. Growth charts were derived from the historical cohort (n = 40). Height gain in the treated population was +0.62 ± 0.81 SDS greater than in the general population, and +1.39 ± 0.9 SDS greater than in the historical untreated HCH cohort (mean gain of 7.4 ± 6.6 cm gain). A negative correlation between height gain and age at treatment initiation was reported (p = 0.04). There was no significant difference in response between patients with fibroblast growth factor receptor 3 mutations and those without. No treatment-related serious adverse events were reported. r-hGH treatment is well tolerated and effective in improving growth in HCH patients, particularly when started early. The treatment effect varies greatly and must be evaluated for each patient during treatment to determine the value of continued therapy. © 2014 S. Karger AG, Basel.

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

PubMed

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

2012-02-15

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

IL4R alpha mutations are associated with asthma exacerbations and mast cell/IgE expression.

PubMed

Wenzel, Sally E; Balzar, Silvana; Ampleford, Elizabeth; Hawkins, Gregory A; Busse, William W; Calhoun, William J; Castro, Mario; Chung, K Fan; Erzurum, Serpil; Gaston, Benjamin; Israel, Elliot; Teague, W Gerald; Curran-Everett, Douglas; Meyers, Deborah A; Bleecker, Eugene R

2007-03-15

Severe asthma has been associated with severe exacerbations, lower lung function and greater tissue inflammation. Previous studies have suggested that mutations in interleukin-4 receptor alpha (IL4Ralpha) are associated with lower lung function, higher IgE, and a gain in receptor function. However, an effect on exacerbations and tissue inflammation has not been shown. Allelic substitutions in IL4Ralpha are associated with asthma exacerbations, lower lung function, and tissue inflammation, in particular to mast cells and IgE. Two well-characterized cohorts of subjects with severe asthma were analyzed for five single nucleotide polymorphisms (SNPs) in IL4Ralpha. These polymorphisms were compared with the history of severe asthma exacerbations and lung function. In the primary (National Jewish) cohort, these polymorphisms were also compared with endobronchial tissue inflammatory cells and local IgE. In both cohorts, the presence of the minor alleles at E375A and Q551R, which were more common in African Americans, was associated with a history of severe exacerbations and lower lung function. In the National Jewish cohort, the C allele at E375A was associated with higher tissue mast cells and higher levels of IgE bound to mast cells. The significance for most of these associations remained when whites (the larger racial subgroup) were analyzed separately. SNPs in IL4Ralpha, which are more common in African Americans, are associated with severe asthma exacerbations, lower lung function, and increased mast cell-related tissue inflammation. Further studies of the impact of these mutations in African Americans and on receptor function are indicated.

Cancer incidence and mortality: A cohort study in China, 2008-2013.

PubMed

Pan, Rui; Zhu, Meng; Yu, Canqing; Lv, Jun; Guo, Yu; Bian, Zheng; Yang, Ling; Chen, Yiping; Hu, Zhibin; Chen, Zhengming; Li, Liming; Shen, Hongbing

2017-10-01

The National Central Cancer Registry of China (NCCR) was the only available source of cancer monitoring in China, even though only about 70% of cancer registration sites were qualified by now. In this study, based on a national large prospective cohort-the China Kadoorie Biobank (CKB), we aimed to provide additional cancer statistics and compare the difference of cancer burden between urban and rural areas of China. A total of 497,693 cancer-free participants aged 35-74 years were recruited and successfully followed up from 2004 to 2013 in 5 urban and 5 rural areas across China. Except for traditional registration systems, the national health insurance system and active follow-up were used to determine new cancer incidents and related deaths. The mortality-to-incidence ratio (MIR) was used to compare the differences of cancer burden between urban and rural areas of China. We found that cancer mortality coincided well between our cohort and NCCR, while the incidence was much higher in our cohort. Based on CKB, we found the MIR of all cancers was 0.54 in rural areas, which was approximately one-third higher than that in urban areas with 0.39. Cancer profiles in urban areas were transiting to Western distributions, which were characterized with high incidences of breast cancer and colorectal cancer; while cancers of the esophagus, liver and cervix uteri were still common in rural areas of China. Our results provide additional cancer statistics of China and demonstrate the differences of cancer burden between urban and rural areas of China. © 2017 UICC.

Rare Copy Number Variation in Treatment-Resistant Major Depressive Disorder

PubMed Central

O’Dushlaine, Colm; Ripke, Stephan; Ruderfer, Douglas M.; Hamilton, Steven P.; Fava, Maurizio; Iosifescu, Dan V.; Kohane, Isaac S.; Churchill, Susanne E.; Castro, Victor M.; Clements, Caitlin C.; Blumenthal, Sarah R.; Murphy, Shawn N.; Smoller, Jordan W.; Perlis, Roy H.

2014-01-01

Background While antidepressant treatment response appears to be partially heritable, no consistent genetic associations have been identified. Large, rare copy number variants (CNVs) play a role in other neuropsychiatric diseases, so we assessed their association with treatment-resistant depression (TRD). Methods We analyzed data from two genome-wide association studies comprising 1263 Caucasian patients with major depressive disorder. One was drawn from a large health system by applying natural language processing to electronic health records (i2b2 cohort). The second consisted of a multicenter study of sequential antidepressant treatments, Sequenced Treatment Alternatives to Relieve Depression. The Birdsuite package was used to identify rare deletions and duplications. Individuals without symptomatic remission, despite two antidepressant treatment trials, were contrasted with those who remitted with a first treatment trial. Results CNV data were derived for 778 subjects in the i2b2 cohort, including 300 subjects (37%) with TRD, and 485 subjects in Sequenced Treatment Alternatives to Relieve Depression cohort, including 152 (31%) with TRD. CNV burden analyses identified modest enrichment of duplications in cases (empirical p = .04 for duplications of 100–200 kilobase) and a particular deletion region spanning gene PABPC4L (empirical p = .02, 6 cases: 0 controls). Pathway analysis suggested enrichment of CNVs intersecting genes regulating actin cytoskeleton. However, none of these associations survived genome-wide correction. Conclusions Contribution of rare CNVs to TRD appears to be modest, individually or in aggregate. The electronic health record-based methodology demonstrated here should facilitate collection of larger TRD cohorts necessary to further characterize these effects. PMID:24529801

Concerted Uranium Research in Europe (CURE): toward a collaborative project integrating dosimetry, epidemiology and radiobiology to study the effects of occupational uranium exposure.

PubMed

Laurent, Olivier; Gomolka, Maria; Haylock, Richard; Blanchardon, Eric; Giussani, Augusto; Atkinson, Will; Baatout, Sarah; Bingham, Derek; Cardis, Elisabeth; Hall, Janet; Tomasek, Ladislav; Ancelet, Sophie; Badie, Christophe; Bethel, Gary; Bertho, Jean-Marc; Bouet, Ségolène; Bull, Richard; Challeton-de Vathaire, Cécile; Cockerill, Rupert; Davesne, Estelle; Ebrahimian, Teni; Engels, Hilde; Gillies, Michael; Grellier, James; Grison, Stephane; Gueguen, Yann; Hornhardt, Sabine; Ibanez, Chrystelle; Kabacik, Sylwia; Kotik, Lukas; Kreuzer, Michaela; Lebacq, Anne Laure; Marsh, James; Nosske, Dietmar; O'Hagan, Jackie; Pernot, Eileen; Puncher, Matthew; Rage, Estelle; Riddell, Tony; Roy, Laurence; Samson, Eric; Souidi, Maamar; Turner, Michelle C; Zhivin, Sergey; Laurier, Dominique

2016-06-01

The potential health impacts of chronic exposures to uranium, as they occur in occupational settings, are not well characterized. Most epidemiological studies have been limited by small sample sizes, and a lack of harmonization of methods used to quantify radiation doses resulting from uranium exposure. Experimental studies have shown that uranium has biological effects, but their implications for human health are not clear. New studies that would combine the strengths of large, well-designed epidemiological datasets with those of state-of-the-art biological methods would help improve the characterization of the biological and health effects of occupational uranium exposure. The aim of the European Commission concerted action CURE (Concerted Uranium Research in Europe) was to develop protocols for such a future collaborative research project, in which dosimetry, epidemiology and biology would be integrated to better characterize the effects of occupational uranium exposure. These protocols were developed from existing European cohorts of workers exposed to uranium together with expertise in epidemiology, biology and dosimetry of CURE partner institutions. The preparatory work of CURE should allow a large scale collaborative project to be launched, in order to better characterize the effects of uranium exposure and more generally of alpha particles and low doses of ionizing radiation.

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.

Two new regions of interest to evaluate separately cortical and trabecular BMD in the proximal femur using DXA.

PubMed

Prevrhal, Sven; Meta, Margarita; Genant, Harry K

2004-01-01

To differentiate changes in trabecular and cortical bone density at a skeletal site bearing body weight, the main goal of this retrospective study was to develop and characterize two new regions of interest (ROIs) for DXA at the hip, one mainly focusing on trabecular bone and another mainly focusing on cortical bone. Specific aims were to maximize the precision of the ROIs and to characterize their usefulness for monitoring age-related bone loss and discriminating controls from fracture cases in a cross-sectional study population and to compare them with earlier ROIs designed by our group. The study used populations from two different previous studies conducted in our laboratory, with one comprising cohorts of healthy premenopausal women, healthy postmenopausal women, and postmenopausal osteoporotic women with at least one spinal fracture (Spine Fx Study) and the other one comprising two cohorts of age-matched postmenopausal women, in whom cases had sustained a hip fracture (Hip Fx study). The new ROI for trabecular bone (CIRCROI) tries to improve on the earlier custom-designed Central ROI, which was also targeted at trabecular bone. CIRCROI consists of an approximate largest circle that can fit inside the femoral proximal metaphysis without touching the superior and inferior endocortical walls. The new ROI for cortical bone (CORTROI) at a site bearing body weight is defined as a horizontal rectangular box crossing the femoral shaft below the lesser trochanter. CORTROI BMD cohort means were significantly higher than all other ROIs, and CIRCROI BMD cohort means were lower than standard ROIs with the exception of Ward's ROI. CIRCROI BMD was highly correlated with total femur BMD ( r=0.94) and Central BMD ( r=0.93), whereas CORTROI BMD correlations were lower (highest with total femur BMD ( r=0.86)). Fracture discrimination odds ratios (ORs) of all ROIs were significant for the Hip Fx Study, with CIRCROI BMD having the highest, and CORTROI BMD the lowest, OR (4.83 and 2.49 per SD, respectively, compared with 3.69 for Ward's ROI as the highest OR of standard ROIs). For the Spine Fx Study, only spinal and trochanteric BMD had significant OR. The new trabecular ROI had good short-term precision, comparable to the standard ROIs at the hip, but improving on that of Ward's triangle, the only standard ROI only including the anterior and posterior cortical walls and therefore more predominantly consisting of trabecular bone than other standard ROIs. The precision of the new cortical ROI was lower than standard DXA ROIs, except for Ward's triangle, but provides unique information on purely cortical bone at a skeletal site bearing body weight.

Methodology Series Module 1: Cohort Studies

PubMed Central

Setia, Maninder Singh

2016-01-01

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

Methodology Series Module 1: Cohort Studies.

PubMed

Setia, Maninder Singh

2016-01-01

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

CKD Self-management: Phenotypes and Associations With Clinical Outcomes.

PubMed

Schrauben, Sarah J; Hsu, Jesse Y; Rosas, Sylvia E; Jaar, Bernard G; Zhang, Xiaoming; Deo, Rajat; Saab, Georges; Chen, Jing; Lederer, Swati; Kanthety, Radhika; Hamm, L Lee; Ricardo, Ana C; Lash, James P; Feldman, Harold I; Anderson, Amanda H

2018-03-24

To slow chronic kidney disease (CKD) progression and its complications, patients need to engage in self-management behaviors. The objective of this study was to classify CKD self-management behaviors into phenotypes and assess the association of these phenotypes with clinical outcomes. Prospective cohort study. Adults with mild to moderate CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. 3,939 participants in the CRIC Study recruited between 2003 and 2008 served as the derivation cohort and 1,560 participants recruited between 2013 and 2015 served as the validation cohort. CKD self-management behavior phenotypes. CKD progression, atherosclerotic events, heart failure events, death from any cause. Latent class analysis stratified by diabetes was used to identify CKD self-management phenotypes based on measures of body mass index, diet, physical activity, blood pressure, smoking status, and hemoglobin A 1c concentration (if diabetic); Cox proportional hazards models. 3 identified phenotypes varied according to the extent of implementation of recommended CKD self-management behaviors: phenotype I characterized study participants with the most recommended behaviors; phenotype II, participants with a mixture of recommended and not recommended behaviors; and phenotype III, participants with minimal recommended behaviors. In multivariable-adjusted models for those with and without diabetes, phenotype III was strongly associated with CKD progression (HRs of 1.82 and 1.49), death (HRs of 1.95 and 4.14), and atherosclerotic events (HRs of 2.54 and 1.90; each P < 0.05). Phenotype II was associated with atherosclerotic events and death among those with and without diabetes. No consensus definition of CKD self-management; limited to baseline behavior data. There are potentially 3 CKD self-management behavior phenotypes that distinguish risk for clinical outcomes. These phenotypes may inform the development of studies and guidelines regarding optimal self-management. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Pharmacokinetics of surotomycin from phase 1 single and multiple ascending dose studies in healthy volunteers.

PubMed

Chandorkar, Gurudatt; Zhan, Qiao; Donovan, Julie; Rege, Shruta; Patino, Hernando

2017-03-28

Surotomycin, a novel, orally administered, cyclic, lipopeptide antibacterial in development for the treatment of Clostridium difficile-associated diarrhea, has demonstrated minimal intestinal absorption in animal models. Safety, tolerability, and plasma pharmacokinetics of single and multiple ascending oral doses (SAD/MAD) of surotomycin in healthy volunteers were characterized in two randomized, double-blind, placebo-controlled, phase 1 studies. Participants were sequentially enrolled into one of four SAD (500, 1000, 2000, 4000 mg surotomycin) or three MAD (250, 500, 1000 mg surotomycin twice/day for 14 days) cohorts. Ten subjects were randomized 4:1 into each cohort to receive surotomycin or placebo. Surotomycin plasma concentrations rose as dose increased (maximum plasma concentration [C max ]: 10.5, 21.5, 66.6, and 86.7 ng/mL). Systemic levels were generally low, with peak median surotomycin plasma concentrations observed 6-12 h after the first dose. In the MAD study, surotomycin plasma concentrations were higher on day 14 (C max : 25.5, 37.6, and 93.5 ng/mL) than on day 1 (C max : 6.8, 11.0, and 21.1 ng/mL for increasing doses), indicating accumulation. In the SAD study, <0.01% of the administered dose was recovered in urine. Mean surotomycin stool concentration from the 1000 mg MAD cohort was 6394 μg/g on day 5. Both cohorts were well tolerated with all adverse events reported as mild to moderate. Both SAD and MAD studies of surotomycin demonstrated minimal systemic exposure, with feces the primary route of elimination following oral administration; consistent with observations with similar compounds, such as fidaxomicin. Results of these phase 1 studies support the continued clinical development of surotomycin for the treatment of Clostridium difficile-associated diarrhea. NCT02835118 and NCT02835105 . Retrospectively registered, July 13 2016.

Plasma apolipoprotein E and Alzheimer disease risk: the AIBL study of aging.

PubMed

Gupta, V B; Laws, S M; Villemagne, V L; Ames, D; Bush, A I; Ellis, K A; Lui, J K; Masters, C; Rowe, C C; Szoeke, C; Taddei, K; Martins, R N

2011-03-22

There is mounting evidence for the contribution of apoE to the pathophysiology of Alzheimer disease (AD). Studies also indicate that plasma apoE levels may reflect disease status, suggesting that apoE is a potential AD biomarker. However, while some studies of apoE levels in plasma have presented correlations with AD pathology, others have not. Thus, there is a lack of consensus as to the suitability of plasma apoE as an AD biomarker. The major objective of this cross-sectional study was to investigate total plasma apoE as well as levels of the apoE4 form in a large, highly characterized cohort which included both healthy controls and participants with early-stage AD. Total apoE and apoE4 were measured in 1,079 individuals drawn from the highly characterized Australian Imaging, Biomarkers and Lifestyle (AIBL) study. Total and isoform-specific plasma apoE levels were then compared with cerebral Aβ load, as assessed by PET using Pittsburgh compound B (PiB). Total apoE and apoE4 levels were found to be significantly lower in patients with AD in the entire cohort, and decrease with Aβ load in the PiB-PET subset. ApoE levels were significantly lower among ε4 homozygous individuals. In APOE ε3/ε4 heterozygote carriers, apoE4 levels decrease, indicating that apoE3 levels increase with disease. Analysis of cross-sectional data from the AIBL study indicates that plasma apoE levels are altered in AD and correlate with AD pathology level. The significance of these findings will be determined in the AIBL longitudinal study of aging. © 2011 by AAN Enterprises, Inc.

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

PubMed

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

2017-04-01

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

Unspecific neurologic symptoms as possible psychogenic complaints.

PubMed

Franz, M; Schepank, H; Schellberg, D

1993-01-01

Prevalence and course of psychogenically influenced symptoms in neurology and their dependence on age and gender are reported. The epidemiological basis of the data is a long-term follow-up investigation of a high-risk population for about 10 years (n = 240): the Mannheim Cohort Study on Epidemiology of Psychogenic Disorders. Seven psychogenic symptoms of neurologic relevance (headache, lumbar and cervical vertebral complaints, functional vertigo, hyperkinesias, pareses, sleep and concentration disturbances) are characterized in regard to frequency, course and diagnostic significance.

Characterizing sleep disorders of adults with tuberous sclerosis complex: a questionnaire-based study and review.

PubMed

van Eeghen, Agnies M; Numis, Adam I; Staley, Brigid A; Therrien, Samuel E; Thibert, Ronald L; Thiele, Elizabeth A

2011-01-01

An adult cohort with tuberous sclerosis complex was investigated for the prevalence of sleep disturbances and the relationship with seizure variables, medication, and psychological functioning. Information on 35 adults was gathered using four questionnaires: Epworth Sleepiness Scale (ESS), Sleep and Epilepsy Questionnaire (SEQ), Sleep Diagnosis List (SDL), and Adult Self-Report Scale (ASR). In addition, clinical, genetic and electrophysiological data were collected. Of 35 respondents, 25 had a history of epilepsy. A subjective sleep disorder was found in 31% of the cohort. Insomnia scores showed a significant positive correlation with obstructive sleep apnea syndrome and restless legs syndrome scores. Significant correlations were found between daytime sleepiness and scores on depression, antisocial behavior, and use of mental health medication. A subgroup using antiepileptic medication showed high correlations between daytime sleepiness, attention deficits, and anxiety scores. Copyright © 2010 Elsevier Inc. All rights reserved.

Soy intake is associated with lower lung cancer risk: results from a meta-analysis of epidemiologic studies123

PubMed Central

Yang, Wan-Shui; Va, Puthiery; Wong, Man-Yu; Zhang, Huan-Ling

2011-01-01

Background: Although several in vitro and animal in vivo studies have suggested that soy or soy isoflavones may exert inhibitory effects on lung carcinogenesis, epidemiologic studies have reported inconclusive results on the association between soy intake and lung cancer. Objective: The aim of this meta-analysis was to investigate whether an association exists between soy and lung cancer in epidemiologic studies. Design: We searched PubMed, EMBASE, and the Cochrane Library from their inception to February 2011 for both case-control and cohort studies that assessed soy consumption and lung cancer risk. Study-specific risk estimates were combined by using fixed-effect or random-effect models. Results: A total of 11 epidemiologic studies that consisted of 8 case-control and 3 prospective cohort studies were included. A significantly inverse association was shown between soy intake and lung cancer with an overall RR of 0.77 (95% CI: 0.65, 0.92). Findings were slightly different when analyses were restricted to 5 high-quality studies (RR: 0.70; 95% CI: 0.45, 0.99). In a subgroup meta-analysis, a statistically significant protective effect of soy consumption was observed in women (RR: 0.79; 95% CI: 0.67, 0.93), never smokers (RR: 0.62; 95% CI: 0.51, 0.76), and Asian populations (RR: 0.86; 95% CI: 0.74, 0.98). Conclusions: Our findings indicate that the consumption of soy food is associated with lower lung cancer risk. Because of different methods used to assess soy consumption across studies, more well-designed cohort studies or intervention studies that use unified measures of soy intake are needed to fully characterize such an association. PMID:22071712

Characterization of Indoor Extremely Low Frequency and Low Frequency Electromagnetic Fields in the INMA-Granada Cohort

PubMed Central

Calvente, Irene; Dávila-Arias, Cristina; Ocón-Hernández, Olga; Pérez-Lobato, Rocío; Ramos, Rosa; Artacho-Cordón, Francisco; Olea, Nicolás; Núñez, María Isabel; Fernández, Mariana F.

2014-01-01

Objective To characterize the exposure to electric fields and magnetic fields of non-ionizing radiation in the electromagnetic spectrum (15 Hz to 100 kHz) in the dwellings of children from the Spanish Environment and Childhood-“INMA” population-based birth cohort. Methodology The study sample was drawn from the INMA-Granada cohort. Out of 300 boys participating in the 9–10 year follow-up, 123 families agreed to the exposure assessment at home and completed a specific ad hoc questionnaire gathering information on sources of non-ionizing radiation electric and magnetic fields inside the homes and on patterns of use. Long-term indoor measurements were carried out in the living room and bedroom. Results Survey data showed a low exposure in the children's homes according to reference levels of the International Commission on Non-Ionizing Radiation Protection but with large differences among homes in mean and maximum values. Daytime electrostatic and magnetic fields were below the quantification limit in 78.6% (92 dwellings) and 92.3% (108 dwellings) of houses, with an arithmetic mean value (± standard deviation) of 7.31±9.32 V/m and 162.30±91.16 nT, respectively. Mean magnetic field values were 1.6 lower during the night than the day. Nocturnal electrostatic values were not measured. Exposure levels were influenced by the area of residence (higher values in urban/semi-urban versus rural areas), type of dwelling, age of dwelling, floor of the dwelling, and season. Conclusion Given the greater sensitivity to extremely low-frequency electromagnetic fields of children and following the precautionary principle, preventive measures are warranted to reduce their exposure. PMID:25192253

Characterization of indoor extremely low frequency and low frequency electromagnetic fields in the INMA-Granada cohort.

PubMed

Calvente, Irene; Dávila-Arias, Cristina; Ocón-Hernández, Olga; Pérez-Lobato, Rocío; Ramos, Rosa; Artacho-Cordón, Francisco; Olea, Nicolás; Núñez, María Isabel; Fernández, Mariana F

2014-01-01

To characterize the exposure to electric fields and magnetic fields of non-ionizing radiation in the electromagnetic spectrum (15 Hz to 100 kHz) in the dwellings of children from the Spanish Environment and Childhood-"INMA" population-based birth cohort. The study sample was drawn from the INMA-Granada cohort. Out of 300 boys participating in the 9-10 year follow-up, 123 families agreed to the exposure assessment at home and completed a specific ad hoc questionnaire gathering information on sources of non-ionizing radiation electric and magnetic fields inside the homes and on patterns of use. Long-term indoor measurements were carried out in the living room and bedroom. Survey data showed a low exposure in the children's homes according to reference levels of the International Commission on Non-Ionizing Radiation Protection but with large differences among homes in mean and maximum values. Daytime electrostatic and magnetic fields were below the quantification limit in 78.6% (92 dwellings) and 92.3% (108 dwellings) of houses, with an arithmetic mean value (± standard deviation) of 7.31±9.32 V/m and 162.30±91.16 nT, respectively. Mean magnetic field values were 1.6 lower during the night than the day. Nocturnal electrostatic values were not measured. Exposure levels were influenced by the area of residence (higher values in urban/semi-urban versus rural areas), type of dwelling, age of dwelling, floor of the dwelling, and season. Given the greater sensitivity to extremely low-frequency electromagnetic fields of children and following the precautionary principle, preventive measures are warranted to reduce their exposure.

Natural history of aortic root dilation through young adulthood in a hypermobile Ehlers-Danlos syndrome cohort.

PubMed

Ritter, Alyssa; Atzinger, Carrie; Hays, Brandon; James, Jeanne; Shikany, Amy; Neilson, Derek; Martin, Lisa; Weaver, Kathryn Nicole

2017-06-01

Hypermobile Ehlers-Danlos syndrome (hEDS) is a common inherited connective tissue disorder characterized by joint hypermobility. The natural history of aortic root dilation (AoD), a potential complication of EDS, has not been well characterized in this population. We describe the natural history of aortic root size in a large cohort of patients with hEDS. A cohort of 325 patients with HEDS was identified at Cincinnati Children's Hospital Medical Center (CCHMC), including 163 patients from a previous study. Medical records were reviewed and each participant's height, weight, and aortic dimensions from up to four echocardiograms were documented. Aortic root z-scores were calculated using two established formulas based on age (Boston or Devereux). Overall prevalence of AoD and prevalence by age were calculated and longitudinal regression was performed. The prevalence of AoD with a z-score ≥ 2.0 was 14.2% (46/325) and with a z-score of ≥3.0 was 5.5% (18/325). No significant increases in z-score were seen over time for patients with multiple echocardiograms. Participants under the age of 15 years had an average decline of 0.1 standard deviations (SDs)/year. No significant change was found after 15 of age. Between the ages of 15 and 21 years, Boston z-scores were 0.96 higher than Devereux z-scores. The nearly 1 z-score unit difference between formulas indicates caution prior to diagnosing AoD in patients with hEDS. In light of the low prevalence and lack of progression of AoD, routine echocardiograms may not be warranted for pediatric patients with hEDS. © 2017 Wiley Periodicals, Inc.

A Quiescent Phase in Human Mortality? Exploring the Ages of Least Vulnerability

PubMed Central

Engelman, Michal; Seplaki, Christopher L.; Varadhan, Ravi

2017-01-01

Demographic studies of mortality often emphasize the two ends of the lifespan, focusing on the declining hazard after birth or the increasing risk of death at older ages. We call attention to the intervening phase, when humans are least vulnerable to the force of mortality, and consider its features in both evolutionary and historical perspectives. We define this quiescent phase (Q-phase) formally, estimate its bounds using life tables for Swedish cohorts born between 1800 and 1920, and describe changes in the morphology of the Q-phase. We show that for cohorts aging during Sweden’s demographic and epidemiological transitions, the Q-phase became longer and more pronounced, reflecting the retreat of infections and maternal mortality as key causes of death. These changes revealed an underlying hazard trajectory that remains relatively low and constant during the prime ages for reproduction and investment in both personal capital and relationships with others. Our characterization of the Q-phase highlights it as a unique, dynamic, and historically contingent cohort feature, whose increased visibility was made possible by the rapid pace of survival improvements in the nineteenth and twentieth centuries. This visibility may be reduced or sustained under subsequent demographic regimes. PMID:28397179

Adolescents and Young Adults with Down Syndrome Presenting to a Medical Clinic with Depression: Phenomenology and Characterization Using the Reiss Scales and Aberrant Behavior Checklist

ERIC Educational Resources Information Center

Capone, George T.; Aidikoff, Jenna M.; Goyal, Parag

2011-01-01

Caretakers of adolescents and young adults with Down syndrome (DS) may report the onset of a depressive illness in previously mentally well individuals. However, the behavioral phenomenology of these conditions has not been well characterized. We ascertained a cohort of DS patient-subjects presenting to a specialty clinic with medical and/or…

Characterizing Pediatric Non-Malarial Fever and Identifying the At-Risk Child in Rural Malawi.

PubMed

Kortz, Teresa Bleakly; Blair, Alden; Scarr, Ellen; Mguntha, Andrew Masozi; Bandawe, Gama; Schell, Ellen; Rankin, Sally; Baltzell, Kimberly

2018-01-01

Objective . To characterize children with non-malarial fever at risk of nonrecovery or worsening in rural Malawi. Methods . This is a subgroup analysis of patients ≤14 years of age from a prospective cohort study in non-malarial fever subjects (temperature ≥37.5°C, or fever within 48 hours, and malaria negative) in southern Malawi cared for at a mobile clinic during the 2016 dry (August to September) or wet (November to December) season. Data collection included chart review and questionnaires; 14-day follow-up was conducted. We conducted univariate descriptive statistics on cohort characteristics, bivariate analyses to examine associations between characteristics and outcomes, and multivariate logistic regressions to explore factors associated with nonrecovery. Results . A total of 2893 patients were screened, 401 were enrolled, 286 of these were children, and 280 children completed follow-up. Eighty-seven percent reported symptom resolution, 12.9% reported no improvement, and there were no deaths or hospitalizations. No improvement was associated with dry season presentation (42.6% vs 75.0%, P < .0003), >2 days of symptoms (51.6% vs 72.2%, P = .03), and food insecurity (62.3% vs 86.1%, P = .007). Dry season subjects had a 4.35 times greater likelihood of nonimprovement (95% confidence interval [CI] = 1.96-11.11). Household food insecurity and being >2 hours from a permanent clinic were associated with no improvement (adjusted odds ratio [AOR] = 4.61, 95% CI = 1.81-14.29; and AOR = 2.38, 95% CI = 1.11-5.36, respectively). Conclusion . Outcomes were generally excellent in this rural, outpatient pediatric cohort, though risk factors for nonrecovery included food insecurity, access to a standing clinic, and seasonality. Ideally, this study will inform clinic- and policy-level changes aimed at ameliorating the modifiable risk factors in Malawi and throughout rural Africa.

Racial and Ethnic Disparities in Nonalcoholic Fatty Liver Disease Prevalence, Severity, and Outcomes in the United States: A Systematic Review and Meta-analysis.

PubMed

Rich, Nicole E; Oji, Stefany; Mufti, Arjmand R; Browning, Jeffrey D; Parikh, Neehar D; Odewole, Mobolaji; Mayo, Helen; Singal, Amit G

2018-02-01

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting 75-100 million Americans. However, the disease burden may not be equally distributed among races or ethnicities. We conducted a systematic review and meta-analysis to characterize racial and ethnic disparities in NAFLD prevalence, severity, and prognosis. We searched MEDLINE, EMBASE, and Cochrane databases through August 2016 for studies that reported NAFLD prevalence in population-based or high-risk cohorts, NAFLD severity including presence of nonalcoholic steatohepatitis (NASH) and significant fibrosis, and NAFLD prognosis including development of cirrhosis complications and mortality. Pooled relative risks, according to race and ethnicity, were calculated for each outcome using the DerSimonian and Laird method for a random-effects model. We identified 34 studies comprising 368,569 unique patients that characterized disparities in NAFLD prevalence, severity, or prognosis. NAFLD prevalence was highest in Hispanics, intermediate in Whites, and lowest in Blacks, although differences between groups were smaller in high-risk cohorts (range 47.6%-55.5%) than population-based cohorts (range, 13.0%-22.9%). Among patients with NAFLD, risk of NASH was higher in Hispanics (relative risk, 1.09; 95% CI, 0.98-1.21) and lower in Blacks (relative risk, 0.72; 95% CI, 0.60-0.87) than Whites. However, the proportion of patients with significant fibrosis did not significantly differ among racial or ethnic groups. Data were limited and discordant on racial or ethnic disparities in outcomes of patients with NAFLD. In a systematic review and meta-analysis, we found significant racial and ethnic disparities in NAFLD prevalence and severity in the United States, with the highest burden in Hispanics and lowest burden in Blacks. However, data are discordant on racial or ethnic differences in outcomes of patients with NAFLD. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Risk-Factor Profile and Comorbidities in 2398 Patients With Newly Diagnosed Hypertension From the Abuja Heart Study.

PubMed

Ojji, Dike B; Libhaber, Elena; Atherton, John J; Abdullahi, Bolaji; Nwankwo, Ada; Sliwa, Karen

2015-09-01

Risk factors, comorbidities, and end-organ damage in newly diagnosed hypertension (HT) are poorly described in larger cohorts of urban African patients undergoing epidemiological transition. We therefore decided to characterize a large cohort of hypertensive subjects presenting to a tertiary health center in sub-Saharan Africa. It is an observational cross-sectional study. We prospectively collected detailed clinical, biochemical, electrocardiography, and echocardiography data of all subjects with HT as the primary diagnosis in patients presenting at the Cardiology Unit of the University of Abuja Teaching Hospital over an 8-year period. Of 2398 subjects, 1187 patients (49.4%) were female with a mean age of 51 ± 12.8 years. Presenting symptoms and signs were most commonly palpitation in 691 (28.8%) followed by dyspnoea on exertion in 541 (22.6%), orthopnea in 532 (22.2%), pedal oedema in 468 (19.5%), paroxysmal nocturnal dyspnoea in 332 (13.8%), whereas only 31 (1.3%) presented with chest pain. Risk factors were obesity in 671 (28%); 523 (21.8%) had total cholesterol >5.2 mmol/L, diabetes mellitus was present in 201 (8.4%) and 187 (7.8%) were smokers. End-organ damage was present in form of echocardiographic left ventricular hypertrophy in 1336 (55.7%) followed by heart failure in 542 (22.6%). Arrhythmias occurred in 110 (4.6%) of cases, cerebrovascular accident in 103 (4.3%), chronic kidney disease in 26 (1.1%), hypertensive encephalopathy in 10 (0.4%), and coronary artery disease in 6 (0.26%). There were marked differences in sex as women were more obese and men presented with more advanced disease. The burden of HT and its complications in this carefully characterized African cohort is quite enormous with more than three-fourth having one form of complication. The need of effective primary and secondary preventive measures to be mapped out to tackle this problem cannot be overemphasized.

Risk-Factor Profile and Comorbidities in 2398 Patients With Newly Diagnosed Hypertension From the Abuja Heart Study

PubMed Central

Ojji, Dike B.; Libhaber, Elena; Atherton, John J.; Abdullahi, Bolaji; Nwankwo, Ada; Sliwa, Karen

2015-01-01

Abstract Risk factors, comorbidities, and end-organ damage in newly diagnosed hypertension (HT) are poorly described in larger cohorts of urban African patients undergoing epidemiological transition. We therefore decided to characterize a large cohort of hypertensive subjects presenting to a tertiary health center in sub-Saharan Africa. It is an observational cross-sectional study. We prospectively collected detailed clinical, biochemical, electrocardiography, and echocardiography data of all subjects with HT as the primary diagnosis in patients presenting at the Cardiology Unit of the University of Abuja Teaching Hospital over an 8-year period. Of 2398 subjects, 1187 patients (49.4%) were female with a mean age of 51 ± 12.8 years. Presenting symptoms and signs were most commonly palpitation in 691 (28.8%) followed by dyspnoea on exertion in 541 (22.6%), orthopnea in 532 (22.2%), pedal oedema in 468 (19.5%), paroxysmal nocturnal dyspnoea in 332 (13.8%), whereas only 31 (1.3%) presented with chest pain. Risk factors were obesity in 671 (28%); 523 (21.8%) had total cholesterol >5.2 mmol/L, diabetes mellitus was present in 201 (8.4%) and 187 (7.8%) were smokers. End-organ damage was present in form of echocardiographic left ventricular hypertrophy in 1336 (55.7%) followed by heart failure in 542 (22.6%). Arrhythmias occurred in 110 (4.6%) of cases, cerebrovascular accident in 103 (4.3%), chronic kidney disease in 26 (1.1%), hypertensive encephalopathy in 10 (0.4%), and coronary artery disease in 6 (0.26%). There were marked differences in sex as women were more obese and men presented with more advanced disease. The burden of HT and its complications in this carefully characterized African cohort is quite enormous with more than three-fourth having one form of complication. The need of effective primary and secondary preventive measures to be mapped out to tackle this problem cannot be overemphasized. PMID:26426662

Brain Entropy Mapping Using fMRI

PubMed Central

Wang, Ze; Li, Yin; Childress, Anna Rose; Detre, John A.

2014-01-01

Entropy is an important trait for life as well as the human brain. Characterizing brain entropy (BEN) may provide an informative tool to assess brain states and brain functions. Yet little is known about the distribution and regional organization of BEN in normal brain. The purpose of this study was to examine the whole brain entropy patterns using a large cohort of normal subjects. A series of experiments were first performed to validate an approximate entropy measure regarding its sensitivity, specificity, and reliability using synthetic data and fMRI data. Resting state fMRI data from a large cohort of normal subjects (n = 1049) from multi-sites were then used to derive a 3-dimensional BEN map, showing a sharp low-high entropy contrast between the neocortex and the rest of brain. The spatial heterogeneity of resting BEN was further studied using a data-driven clustering method, and the entire brain was found to be organized into 7 hierarchical regional BEN networks that are consistent with known structural and functional brain parcellations. These findings suggest BEN mapping as a physiologically and functionally meaningful measure for studying brain functions. PMID:24657999

Individual differences in online spoken word recognition: Implications for SLI

PubMed Central

McMurray, Bob; Samelson, Vicki M.; Lee, Sung Hee; Tomblin, J. Bruce

2012-01-01

Thirty years of research has uncovered the broad principles that characterize spoken word processing across listeners. However, there have been few systematic investigations of individual differences. Such an investigation could help refine models of word recognition by indicating which processing parameters are likely to vary, and could also have important implications for work on language impairment. The present study begins to fill this gap by relating individual differences in overall language ability to variation in online word recognition processes. Using the visual world paradigm, we evaluated online spoken word recognition in adolescents who varied in both basic language abilities and non-verbal cognitive abilities. Eye movements to target, cohort and rhyme objects were monitored during spoken word recognition, as an index of lexical activation. Adolescents with poor language skills showed fewer looks to the target and more fixations to the cohort and rhyme competitors. These results were compared to a number of variants of the TRACE model (McClelland & Elman, 1986) that were constructed to test a range of theoretical approaches to language impairment: impairments at sensory and phonological levels; vocabulary size, and generalized slowing. None were strongly supported, and variation in lexical decay offered the best fit. Thus, basic word recognition processes like lexical decay may offer a new way to characterize processing differences in language impairment. PMID:19836014

Predictors of peer victimization among Peruvian adolescents in the young lives cohort.

PubMed

Lister, Cameron; Merrill, Ray M; Vance, David; West, Joshua H; Hall, P Cougar; Crookston, Benjamin T

2015-02-01

Bully-victimization is a widespread public health issue with significant negative effects on both social function and psychological well-being. Existing research in Peru shows high prevalence of bullying. However, researchers have yet to fully understand the phenomenon of victimization in developing regions. The purpose of this study was to characterize victimization patterns over time, along with the predictors of victimization from a cohort of Peruvian adolescents enrolled in the young lives (YL) study. This study examined data from YL, a longitudinal study of poverty, health, and development, which examined data from the older cohort of children in Peru across three rounds (ages 8, 12, and 15 years). The sample consisted of 714 children from 74 communities that represent 20 districts in Peru. After adjusting for urban/rural setting, there remained a significantly lower wealth index for children who were bullied at ages 8 and 12 years. Exploratory analysis showed that although those in the lowest quartile of body mass index (BMI) were significantly more likely to be bullied at age 8 years, this association waned over time. A worse caregiver assessment of child's health compared with others was associated with a significantly greater risk of bully-victimization. At age 8 years, caregiver education was significantly lower among those bullied compared with those who were not bullied. This study showed several factors as the predictors of victimization in the early years, including being male and having low BMI, low socioeconomic status, and low parental/caregiver education. Further longitudinal studies should be conducted to determine the extent to which these predictors vary in significance over time.

Omics analysis of human bone to identify genes and molecular networks regulating skeletal remodeling in health and disease.

PubMed

Reppe, Sjur; Datta, Harish K; Gautvik, Kaare M

2017-08-01

The skeleton is a metabolically active organ throughout life where specific bone cell activity and paracrine/endocrine factors regulate its morphogenesis and remodeling. In recent years, an increasing number of reports have used multi-omics technologies to characterize subsets of bone biological molecular networks. The skeleton is affected by primary and secondary disease, lifestyle and many drugs. Therefore, to obtain relevant and reliable data from well characterized patient and control cohorts are vital. Here we provide a brief overview of omics studies performed on human bone, of which our own studies performed on trans-iliacal bone biopsies from postmenopausal women with osteoporosis (OP) and healthy controls are among the first and largest. Most other studies have been performed on smaller groups of patients, undergoing hip replacement for osteoarthritis (OA) or fracture, and without healthy controls. The major findings emerging from the combined studies are: 1. Unstressed and stressed bone show profoundly different gene expression reflecting differences in bone turnover and remodeling and 2. Omics analyses comparing healthy/OP and control/OA cohorts reveal characteristic changes in transcriptomics, epigenomics (DNA methylation), proteomics and metabolomics. These studies, together with genome-wide association studies, in vitro observations and transgenic animal models have identified a number of genes and gene products that act via Wnt and other signaling systems and are highly associated to bone density and fracture. Future challenge is to understand the functional interactions between bone-related molecular networks and their significance in OP and OA pathogenesis, and also how the genomic architecture is affected in health and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Getting to the Heart of Cardiovascular Risk Assessment in Astronauts for Exploration Class Missions

NASA Technical Reports Server (NTRS)

Elgart, S. R.; Shavers, M. R.; Chappell, L.; Milder, C. M.; Huff, J. L.; Semones, E. J.; Simonsen, L. C.; Patel, Z. S.

2017-01-01

Since the beginning of manned spaceflight, NASA has recognized the potential risk of cardiovascular decrements due to stressors in the space environment. Of particular concern is the effect of space radiation on cardiovascular disease since astronauts will be exposed to higher levels of galactic cosmic rays outside the Earth's protective magnetosphere. To date, only a few studies have examined the effects of heavy ion radiation on cardiovascular disease, and at lower, space-relevant doses, the association between radiation exposure and cardiovascular pathology is more varied and unclear. Furthermore, other spaceflight conditions such as microgravity, circadian shifts, and confinement stress pose unique challenges in estimating the health risks that can be attributed to exposure to ionizing radiations. In this work, we review age, cause of mortality, and radiation exposure amongst early NASA astronauts in selection groups and discuss the limitations of assessing such a cohort when attempting to characterize the risk of space flight, including stressors such as space radiation and microgravity exposure, on cardiovascular health. METHODS: NASA astronauts in selection groups 1-7 were chosen and the comparison population was white men of the same birth cohort as drawn from data from the CDC Wonder Database and CDC National Center for Health Statistics Life Tables. Cause of death information was obtained from the Lifetime Surveillance of Astronaut Health program and deceased astronauts were classified based on ICD-10 codes: ischemic heart disease (IHD), stroke, cancer, acute occupational events, non-NASA accidents, and other/unknown. Expected years of life left and expected age at death were calculated for the cohort. RESULTS AND CONCLUSIONS: There were 32 deaths in this early astronaut population, 12 of which were due to accidents or acute occupational events that impacted lifespan considerably. The average age at death from these causes is 30 years lower than the average expected 70 years of age in the general population. Remarkably, all 41 living early astronauts outlived our calculated expected age at death for members of their birth cohort; furthermore, 13 of the 20 deceased astronauts who did not die in NASA/non-NASA accidents exceeded this age. There was no difference in IHD between the astronaut cohort and the comparison population; therefore, it is not possible to associate IHD mortality with radiation in that astronaut cohort. As NASA looks toward future exploration-class missions, early astronaut cohorts provide a convenient option for assessing these risks and for developing mitigation strategies. However, many challenges still exist when assessing such limited evidence, including small cohort size, health and lifestyle confounders (such as smoking and drinking), the high accident mortality rate, and the fact that many of these astronauts are still alive, outliving many of their birth-cohort peers. Future analysis should include a longitudinal study, monitoring cases as they occur in the cohort. As this cohort is currently followed-up over time, and as more IHD cases are anticipated in a population of this age, this type of study is not as resource-intensive as would normally be the case.

Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A.

PubMed

Coyle, T E; Reding, M T; Lin, J C; Michaels, L A; Shah, A; Powell, J

2014-04-01

BAY 94-9027 is a B-domain-deleted recombinant factor VIII (rFVIII) with site-specific attachment of poly(ethylene glycol) that has shown an extended half-life in animal models of hemophilia. To assess the pharmacokinetics and safety of BAY 94-9027 after single and repeated administration in subjects with severe hemophilia A. This 8-week, prospective, multicenter, open-label, phase I trial was conducted in 14 subjects aged 21–58 years with FVIII of < 1%, ≥ 150 days of exposure to FVIII, and no history of FVIII inhibitors. After a ≥ 3-day washout, subjects received a single dose of sucrose-formulated rFVIII (rFVIII-FS) (cohort 1 [n = 7], 25 IU kg−1; cohort 2 [n = 7], 50 IU kg−1) for a 48-h pharmacokinetic (PK) study. After another ≥ 3-day washout, cohort 1 received twice-weekly BAY 94-9027 at 25 IU kg−1 (16 doses), and cohort 2 received once-weekly BAY 94-9027 at 60 IU kg−1 (nine doses). A 168-h PK study was performed after the first and last BAY 94-9027 doses. BAY 94-9027 showed equivalent recovery and an improved PK profile vs. rFVIII-FS, with a half-life of ~ 19 h (vs. ~ 13.0 h for rFVIII-FS). BAY 94-9027 was well tolerated, and no immunogenicity was observed. This phase I study demonstrates that BAY 94-9027 has an extended half-life in subjects with hemophilia A and, after multiple dosing, was well tolerated with no immunogenicity during the 8-week trial. A phase III study in a larger number of subjects is underway to fully characterize how this prolonged half-life will permit less frequent prophylaxis dosing for patients with hemophilia.

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

PubMed

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

2017-01-01

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

Diagnosis of pernicious anemia and the risk of pancreatic cancer.

PubMed

Shah, Pari; Rhim, Andrew D; Haynes, Kevin; Hwang, Wei-Ting; Yang, Yu-Xiao

2014-04-01

A number of studies have demonstrated a trophic effect of gastrin on pancreatic cancer cells in vitro. Pernicious anemia (PA) is a clinical condition characterized by chronic hypergastrinemia. The aim of this study was to determine if PA is a risk factor for pancreatic cancer. This study is a retrospective cohort study using The Health Improvement Network database, which contains comprehensive health information on 7.5 million patients in the United Kingdom from 1993 to 2009. All patients with PA in the study cohort were identified and composed of the exposed group. Each exposed patient was matched on practice site, sex, and age with up to 4 unexposed patients without PA. The outcome was incident pancreatic cancer. The hazard ratio and 95% confidence intervals were estimated using multivariable Cox regression analysis. We identified 15,324 patients with PA and 55,094 unexposed patients. Mean follow-up time was similar between groups (exposed 4.31 [SD, 3.38] years, unexposed 4.63 [SD, 3.44] years). The multivariable adjusted hazard ratio for pancreatic cancer associated with PA was 1.16 (95% confidence interval, 0.77-1.76; P = 0.47). There is no significant association between PA and the risk of pancreatic cancer.

Epidemiologic tools to study the influence of environmental factors on fecundity and pregnancy-related outcomes.

PubMed

Slama, Rémy; Ballester, Ferran; Casas, Maribel; Cordier, Sylvaine; Eggesbø, Merete; Iniguez, Carmen; Nieuwenhuijsen, Mark; Philippat, Claire; Rey, Sylvie; Vandentorren, Stéphanie; Vrijheid, Martine

2014-01-01

Adverse pregnancy outcomes entail a large health burden for the mother and offspring; a part of it might be avoided by better understanding the role of environmental factors in their etiology. Our aims were to review the assessment tools to characterize fecundity troubles and pregnancy-related outcomes in human populations and their sensitivity to environmental factors. For each outcome, we reviewed the possible study designs, main sources of bias, and their suggested cures. In terms of study design, for most pregnancy outcomes, cohorts with recruitment early during or even before pregnancy allow efficient characterization of pregnancy-related events, time-varying confounders, and in utero exposures that may impact birth outcomes and child health. Studies on congenital anomalies require specific designs, assessment of anomalies in medical pregnancy terminations, and, for congenital anomalies diagnosed postnatally, follow-up during several months after birth. Statistical analyses should take into account environmental exposures during the relevant time windows; survival models are an appropriate approach for fecundity, fetal loss, and gestational duration/preterm delivery. Analysis of gestational duration could distinguish pregnancies according to delivery induction (and possibly pregnancy-related conditions). In conclusion, careful design and analysis are required to better characterize environmental effects on human reproduction.

[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.

Optimizing Millennials' Communication Styles

ERIC Educational Resources Information Center

Hartman, Jackie L.; McCambridge, Jim

2011-01-01

Millennials, those individuals born between 1980 and 2000, compose the largest cohort of college students in the United States. Stereotypical views of millennials characterize them as technologically sophisticated multitaskers, capable of significant contributions to tomorrow's organizations, yet deficient in communication skills. This article…

The Genome of the Netherlands: design, and project goals.

PubMed

Boomsma, Dorret I; Wijmenga, Cisca; Slagboom, Eline P; Swertz, Morris A; Karssen, Lennart C; Abdellaoui, Abdel; Ye, Kai; Guryev, Victor; Vermaat, Martijn; van Dijk, Freerk; Francioli, Laurent C; Hottenga, Jouke Jan; Laros, Jeroen F J; Li, Qibin; Li, Yingrui; Cao, Hongzhi; Chen, Ruoyan; Du, Yuanping; Li, Ning; Cao, Sujie; van Setten, Jessica; Menelaou, Androniki; Pulit, Sara L; Hehir-Kwa, Jayne Y; Beekman, Marian; Elbers, Clara C; Byelas, Heorhiy; de Craen, Anton J M; Deelen, Patrick; Dijkstra, Martijn; den Dunnen, Johan T; de Knijff, Peter; Houwing-Duistermaat, Jeanine; Koval, Vyacheslav; Estrada, Karol; Hofman, Albert; Kanterakis, Alexandros; Enckevort, David van; Mai, Hailiang; Kattenberg, Mathijs; van Leeuwen, Elisabeth M; Neerincx, Pieter B T; Oostra, Ben; Rivadeneira, Fernanodo; Suchiman, Eka H D; Uitterlinden, Andre G; Willemsen, Gonneke; Wolffenbuttel, Bruce H; Wang, Jun; de Bakker, Paul I W; van Ommen, Gert-Jan; van Duijn, Cornelia M

2014-02-01

Within the Netherlands a national network of biobanks has been established (Biobanking and Biomolecular Research Infrastructure-Netherlands (BBMRI-NL)) as a national node of the European BBMRI. One of the aims of BBMRI-NL is to enrich biobanks with different types of molecular and phenotype data. Here, we describe the Genome of the Netherlands (GoNL), one of the projects within BBMRI-NL. GoNL is a whole-genome-sequencing project in a representative sample consisting of 250 trio-families from all provinces in the Netherlands, which aims to characterize DNA sequence variation in the Dutch population. The parent-offspring trios include adult individuals ranging in age from 19 to 87 years (mean=53 years; SD=16 years) from birth cohorts 1910-1994. Sequencing was done on blood-derived DNA from uncultured cells and accomplished coverage was 14-15x. The family-based design represents a unique resource to assess the frequency of regional variants, accurately reconstruct haplotypes by family-based phasing, characterize short indels and complex structural variants, and establish the rate of de novo mutational events. GoNL will also serve as a reference panel for imputation in the available genome-wide association studies in Dutch and other cohorts to refine association signals and uncover population-specific variants. GoNL will create a catalog of human genetic variation in this sample that is uniquely characterized with respect to micro-geographic location and a wide range of phenotypes. The resource will be made available to the research and medical community to guide the interpretation of sequencing projects. The present paper summarizes the global characteristics of the project.

Outdoor characterization of radio frequency electromagnetic fields in a Spanish birth cohort.

PubMed

Calvente, I; Fernández, M F; Pérez-Lobato, R; Dávila-Arias, C; Ocón, O; Ramos, R; Ríos-Arrabal, S; Villalba-Moreno, J; Olea, N; Núñez, M I

2015-04-01

There is considerable public concern in many countries about the possible adverse effects of exposure to non-ionizing radiation electromagnetic fields, especially in vulnerable populations such as children. The aim of this study was to characterize environmental exposure profiles within the frequency range 100kHz-6GHz in the immediate surrounds of the dwellings of 123 families from the INMA-Granada birth cohort in Southern Spain, using spot measurements. The arithmetic mean root mean-square electric field (ERMS) and power density (SRMS) values were, respectively, 195.79mV/m (42.3% of data were above this mean) and 799.01µW/m(2) (30% of values were above this mean); median values were 148.80mV/m and 285.94µW/m(2), respectively. Exposure levels below the quantification limit were assigned a value of 0.01V/m. Incident field strength levels varied widely among different areas or towns/villages, demonstrating spatial variability in the distribution of exposure values related to the surface area population size and also among seasons. Although recorded values were well below International Commission for Non-Ionizing Radiation Protection reference levels, there is a particular need to characterize incident field strength levels in vulnerable populations (e.g., children) because of their chronic and ever-increasing exposure. The effects of incident field strength have not been fully elucidated; however, it may be appropriate to apply the precautionary principle in order to reduce exposure in susceptible groups. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-08-01

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

Associations of Posthemodialysis Weights above and below Target Weight with All-Cause and Cardiovascular Mortality

PubMed Central

Kshirsagar, Abhijit V.; Falk, Ronald J.; Brunelli, Steven M.

2015-01-01

Background and objectives Fluid removal via ultrafiltration is a primary function of hemodialysis, and inadequate volume control is associated with significant morbidity and mortality among chronic dialysis patients. Treatment-to-treatment fluid removal goals are typically calculated on the basis of interdialytic weight gain and prescribed target weight. The clinical effect of frequent missed target weights is unclear. This study was designed to evaluate the associations of postdialysis weights above and below the prescribed target weight (separately) and outcomes. Design, setting, participants, & measurements Data were taken from a national cohort of 10,785 prevalent, thrice-weekly, in-center hemodialysis patients dialyzing from 2005 to 2008 (median time at risk, 2.1 [25th percentile, 75th percentile] years) at a single dialysis organization. Patients were characterized as having an above target weight miss if their postdialysis weight was >2 kg above target weight in at least 30% of baseline treatments (14.6% of cohort), or they were characterized as control otherwise. Below target weight miss characterization was analogous for patients with postdialysis weight >2 kg below target weight (6.6% of cohort). Coprimary endpoints were all-cause and cardiovascular mortality. Results Above target weight miss in at least 30% of treatments (versus not) was associated with greater all-cause mortality (adjusted hazard ratio, 1.28; 95% confidence interval, 1.15 to 1.43); and below target weight miss in at least 30% of treatments (versus not) was associated with greater all-cause mortality (adjusted hazard ratio, 1.22; 95% confidence interval, 1.05 to 1.40). Both above and below target weight misses were also significantly associated with greater cardiovascular mortality. Secondary analyses demonstrated dose-response relationships between target weight misses and mortality. Results from sensitivity analyses considering the difference in postdialysis and target weights as a proportion of body weight were analogous to the primary results. Conclusions Postdialysis weights >2 kg above and below target weight are associated with higher all-cause and cardiovascular mortality. Consistent target weight achievement is a viable target for improving fluid management. PMID:25862779

Detection of 22 common leukemic fusion genes using a single-step multiplex qRT-PCR-based assay.

PubMed

Lyu, Xiaodong; Wang, Xianwei; Zhang, Lina; Chen, Zhenzhu; Zhao, Yu; Hu, Jieying; Fan, Ruihua; Song, Yongping

2017-07-25

Fusion genes generated from chromosomal translocation play an important role in hematological malignancies. Detection of fusion genes currently employ use of either conventional RT-PCR methods or fluorescent in situ hybridization (FISH), where both methods involve tedious methodologies and require prior characterization of chromosomal translocation events as determined by cytogenetic analysis. In this study, we describe a real-time quantitative reverse transcription PCR (qRT-PCR)-based multi-fusion gene screening method with the capacity to detect 22 fusion genes commonly found in leukemia. This method does not require pre-characterization of gene translocation events, thereby facilitating immediate diagnosis and therapeutic management. We performed fluorescent qRT-PCR (F-qRT-PCR) using a commercially-available multi-fusion gene detection kit on a patient cohort of 345 individuals comprising 108 cases diagnosed with acute myeloid leukemia (AML) for initial evaluation; remaining patients within the cohort were assayed for confirmatory diagnosis. Results obtained by F-qRT-PCR were compared alongside patient analysis by cytogenetic characterization. Gene translocations detected by F-qRT-PCR in AML cases were diagnosed in 69.4% of the patient cohort, which was comparatively similar to 68.5% as diagnosed by cytogenetic analysis, thereby demonstrating 99.1% concordance. Overall gene fusion was detected in 53.7% of the overall patient population by F-qRT-PCR, 52.9% by cytogenetic prediction in leukemia, and 9.1% in non-leukemia patients by both methods. The overall concordance rate was calculated to be 99.0%. Fusion genes were detected by F-qRT-PCR in 97.3% of patients with CML, followed by 69.4% with AML, 33.3% with acute lymphoblastic leukemia (ALL), 9.1% with myelodysplastic syndromes (MDS), and 0% with chronic lymphocytic leukemia (CLL). We describe the use of a F-qRT-PCR-based multi-fusion gene screening method as an efficient one-step diagnostic procedure as an effective alternative to lengthy conventional diagnostic procedures requiring both cytogenetic analysis followed by targeted quantitative reverse transcription (qRT-PCR) methods, thus allowing timely patient management.

Neuroanatomical morphometric characterization of sex differences in youth using statistical learning.

PubMed

Sepehrband, Farshid; Lynch, Kirsten M; Cabeen, Ryan P; Gonzalez-Zacarias, Clio; Zhao, Lu; D'Arcy, Mike; Kesselman, Carl; Herting, Megan M; Dinov, Ivo D; Toga, Arthur W; Clark, Kristi A

2018-05-15

Exploring neuroanatomical sex differences using a multivariate statistical learning approach can yield insights that cannot be derived with univariate analysis. While gross differences in total brain volume are well-established, uncovering the more subtle, regional sex-related differences in neuroanatomy requires a multivariate approach that can accurately model spatial complexity as well as the interactions between neuroanatomical features. Here, we developed a multivariate statistical learning model using a support vector machine (SVM) classifier to predict sex from MRI-derived regional neuroanatomical features from a single-site study of 967 healthy youth from the Philadelphia Neurodevelopmental Cohort (PNC). Then, we validated the multivariate model on an independent dataset of 682 healthy youth from the multi-site Pediatric Imaging, Neurocognition and Genetics (PING) cohort study. The trained model exhibited an 83% cross-validated prediction accuracy, and correctly predicted the sex of 77% of the subjects from the independent multi-site dataset. Results showed that cortical thickness of the middle occipital lobes and the angular gyri are major predictors of sex. Results also demonstrated the inferential benefits of going beyond classical regression approaches to capture the interactions among brain features in order to better characterize sex differences in male and female youths. We also identified specific cortical morphological measures and parcellation techniques, such as cortical thickness as derived from the Destrieux atlas, that are better able to discriminate between males and females in comparison to other brain atlases (Desikan-Killiany, Brodmann and subcortical atlases). Copyright © 2018 Elsevier Inc. All rights reserved.

Association of tobacco habits, including bidi smoking, with overall and site-specific cancer incidence: results from the Mumbai cohort study

PubMed Central

Pednekar, Mangesh S.; Gupta, Prakash C.; Yeole, Balkrishna B.; Hébert, James R.

2013-01-01

Objective Bidis are hand-rolled cigarettes commonly smoked in South Asia and are marketed to Western populations as a safer alternative to conventional cigarettes. This study examined the association between bidis and other forms of tobacco use and cancer incidence in an urban developing country population. Methods Using data from the large, well-characterized Mumbai cohort study, adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed from Cox proportional hazards regression models in order to compare the relative effect of various forms of tobacco use on cancer incidence. Results During 649,228 person-years of follow-up 1,267 incident cancers occurred in 87,222 male cohort members. Incident oral cancer in bidi smokers (HR = 3.55; 95% CI = 2.40,5.24) was 42% higher than in cigarette smokers (HR = 2.50;95% CI = 1.65,3.78). For all respiratory and intrathoracic organs combined, the increase was 69% (HR = 5.54; 95% CI = 3.46,8.87 vs. HR = 3.28; 95% CI = 1.99,5.39); for lung and larynx, the increases were 35 and 112%, respectively. Smokeless tobacco use was associated with cancers of the lip, oral cavity, pharynx, digestive, respiratory, and intrathoracic organs. Conclusions Despite marketing claims to the contrary, we found that smokeless tobacco use and bidi smoking are at least as harmful as cigarette smoking for all incident cancers and are associated with increased risk of oral and respiratory/intrathoracic cancers. PMID:21431915

Aortic PWV in Chronic Kidney Disease: A CRIC Ancillary Study

PubMed Central

Townsend, Raymond R.; Wimmer, Neil J.; Chirinos, Julio A.; Parsa, Afshin; Weir, Matthew; Perumal, Kalyani; Lash, James P.; Chen, Jing; Steigerwalt, Susan P.; Flack, John; Go, Alan S.; Rafey, Mohammed; Rahman, Mahboob; Sheridan, Angela; Gadegbeku, Crystal A.; Robinson, Nancy A.; Joffe, Marshall

2009-01-01

Background Aortic PWV is a measure of arterial stiffness and has proved useful in predicting cardiovascular morbidity and mortality in several populations of patients, including the healthy elderly, hypertensives and those with end stage renal disease receiving hemodialysis. Little data exist characterizing aortic stiffness in patients with chronic kidney disease who are not receiving dialysis, and in particular the effect of reduced kidney function on aortic PWV. Methods We performed measurements of aortic PWV in a cross-sectional cohort of participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study to determine factors which predict increased aortic PWV in chronic kidney disease. Results PWV measurements were obtained in 2564 participants. The tertiles of aortic PWV (adjusted for waist circumference) were < 7.7 m/sec, 7.7–10.2 m/sec and > 10.2 m/sec with an overall mean (± S.D.) value of 9.48 ± 3.03 m/sec [95% CI = 9.35–9.61 m/sec]. Multivariable regression identified significant independent positive associations of age, blood glucose concentrations, race, waist circumference, mean arterial blood pressure, gender, and presence of diabetes with aortic PWV and a significant negative association with the level of kidney function. Conclusions The large size of this unique cohort, and the targeted enrollment of chronic kidney disease participants provides an ideal situation to study the role of reduced kidney function as a determinant of arterial stiffness. Arterial stiffness may be a significant component of the enhanced cardiovascular risk associated with kidney failure. PMID:20019670

Aortic PWV in chronic kidney disease: a CRIC ancillary study.

PubMed

Townsend, Raymond R; Wimmer, Neil J; Chirinos, Julio A; Parsa, Afshin; Weir, Matthew; Perumal, Kalyani; Lash, James P; Chen, Jing; Steigerwalt, Susan P; Flack, John; Go, Alan S; Rafey, Mohammed; Rahman, Mahboob; Sheridan, Angela; Gadegbeku, Crystal A; Robinson, Nancy A; Joffe, Marshall

2010-03-01

Aortic pulse wave velocity (PWV) is a measure of arterial stiffness and has proved useful in predicting cardiovascular morbidity and mortality in several populations of patients, including the healthy elderly, hypertensives and those with end-stage renal disease receiving hemodialysis. Little data exist characterizing aortic stiffness in patients with chronic kidney disease (CKD) who are not receiving dialysis, and in particular the effect of reduced kidney function on aortic PWV. We performed measurements of aortic PWV in a cross-sectional cohort of participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study to determine factors which predict increased aortic PWV in CKD. PWV measurements were obtained in 2,564 participants. The tertiles of aortic PWV (adjusted for waist circumference) were <7.7 m/s, 7.7-10.2 m/s, and >10.2 m/s with an overall mean (+/- s.d.) value of 9.48 +/- 3.03 m/s (95% confidence interval = 9.35-9.61 m/s). Multivariable regression identified significant independent positive associations of age, blood glucose concentrations, race, waist circumference, mean arterial blood pressure, gender, and presence of diabetes with aortic PWV and a significant negative association with the level of kidney function. The large size of this unique cohort, and the targeted enrollment of CKD participants provides an ideal situation to study the role of reduced kidney function as a determinant of arterial stiffness. Arterial stiffness may be a significant component of the enhanced cardiovascular risk associated with kidney failure.

Characterization and novel analyses of acute stress response patterns in a population-based cohort of young adults: influence of gender, smoking, and BMI.

PubMed

Herbison, Carly E; Henley, David; Marsh, Julie; Atkinson, Helen; Newnham, John P; Matthews, Stephen G; Lye, Stephen J; Pennell, Craig E

2016-01-01

Dysregulation of the biological stress response system has been implicated in the development of psychological, metabolic, and cardiovascular disease. Whilst changes in stress response are often quantified as an increase or decrease in cortisol levels, three different patterns of stress response have been reported in the literature for the Trier Social Stress Test (TSST) (reactive-responders (RR), anticipatory-responders (AR) and non-responders (NR)). However, these have never been systematically analyzed in a large population-based cohort. The aims of this study were to examine factors that contribute to TSST variation (gender, oral contraceptive use, menstrual cycle phase, smoking, and BMI) using traditional methods and novel analyses of stress response patterns. We analyzed the acute stress response of 798, 18-year-old participants from a community-based cohort using the TSST. Plasma adrenocorticotrophic hormone, plasma cortisol, and salivary cortisol levels were quantified. RR, AR, and NR patterns comprised 56.6%, 26.2%, and 17.2% of the cohort, respectively. Smokers were more likely to be NR than (RR or AR; adjusted, p < 0.05). Overweight and obese subjects were less likely to be NR than the other patterns (adjusted, p < 0.05). Males were more likely to be RR than NR (adjusted, p = 0.05). In addition, we present a novel AUC measure (AUCR), for use when the TSST baseline concentration is higher than later time points. These results show that in a young adult cohort, stress-response patterns, in addition to other parameters vary with gender, smoking, and BMI. The distribution of these patterns has the potential to vary with adult health and disease and may represent a biomarker for future investigation.

Pharmacokinetic Profile and Tolerability of Liposomal Bupivacaine Following a Repeated Dose via Local Subcutaneous Infiltration in Healthy Volunteers.

PubMed

Rice, David; Heil, Justin W; Biernat, Lukasz

2017-03-01

Liposomal bupivacaine is indicated for administration into the surgical site to produce post-surgical analgesia. The objectives of this study were to characterize the pharmacokinetic and safety profiles of liposomal bupivacaine following a repeated dose in healthy volunteers. Healthy adults were assigned to receive liposomal bupivacaine via subcutaneous infiltration in a single 266 mg dose (cohort 1) or in two 266 mg doses, with the second dose given immediately, 24, 48, or 72 h after the first dose (cohorts 2-5). Pharmacokinetic parameters were estimated from blood samples collected up to day 14. Subjects were monitored for adverse events and assessed for neurologic function, cardiac function, and infiltration area abnormalities. Twelve subjects were assigned to each cohort. The mean ± standard deviation maximum observed plasma concentration (C max ) of bupivacaine after a single dose was 129 ± 47 ng/mL. The mean C max after the second dose was higher, but always less than double the C max for cohort 1. The highest individual C max (589 ng/mL) was observed in a subject who received the second dose 24 h after the first dose (cohort 4), but was well below the reported thresholds for neurotoxicity and cardiac toxicity (2000 and 4000 ng/mL, respectively). A single and repeated dose were well-tolerated, and there were no clinically meaningful findings regarding neurologic examinations and electrocardiography. The mean C max following a repeated dose of liposomal bupivacaine remained well below accepted values for central nervous system and cardiac toxicity. Liposomal bupivacaine was well-tolerated and revealed no clinically important safety signals. CLINICALTRIALS. NCT02210247.

Predictors and Impact of Self-Reported Suboptimal Effort on Estimates of Prevalence of HIV-Associated Neurocognitive Disorders.

PubMed

Levine, Andrew J; Martin, Eileen; Sacktor, Ned; Munro, Cynthia; Becker, James

2017-06-01

Prevalence estimates of HIV-associated neurocognitive disorders (HAND) may be inflated. Estimates are determined via cohort studies in which participants may apply suboptimal effort on neurocognitive testing, thereby inflating estimates. Additionally, fluctuating HAND severity over time may be related to inconsistent effort. To address these hypotheses, we characterized effort in the Multicenter AIDS Cohort Study. After neurocognitive testing, 935 participants (525 HIV- and 410 HIV+) completed the visual analog effort scale (VAES), rating their effort from 0% to 100%. Those with <100% then indicated the reason(s) for suboptimal effort. K-means cluster analysis established 3 groups: high (mean = 97%), moderate (79%), and low effort (51%). Rates of HAND and other characteristics were compared between the groups. Linear regression examined the predictors of VAES score. Data from 57 participants who completed the VAES at 2 visits were analyzed to characterize the longitudinal relationship between effort and HAND severity. Fifty-two percent of participants reported suboptimal effort (<100%), with no difference between serostatus groups. Common reasons included "tired" (43%) and "distracted" (36%). The lowest effort group had greater asymptomatic neurocognitive impairment and minor neurocognitive disorder diagnosis (25% and 33%) as compared with the moderate (23% and 15%) and the high (12% and 9%) effort groups. Predictors of suboptimal effort were self-reported memory impairment, African American race, and cocaine use. Change in effort between baseline and follow-up correlated with change in HAND severity. Suboptimal effort seems to inflate estimated HAND prevalence and explain fluctuation of severity over time. A simple modification of study protocols to optimize effort is indicated by the results.

Constitutional bone impairment in Noonan syndrome.

PubMed

Baldassarre, Giuseppina; Mussa, Alessandro; Carli, Diana; Molinatto, Cristina; Ferrero, Giovanni Battista

2017-03-01

Noonan syndrome (NS) is an autosomal dominant trait characterized by genotypic and phenotypic variability. It belongs to the Ras/MAPK pathway disorders collectively named Rasopathies or neurocardiofaciocutaneous syndromes. Phenotype is characterized by short stature, congenital heart defects, facial dysmorphisms, skeletal and ectodermal anomalies, cryptorchidism, mild to moderate developmental delay/learning disability, and tumor predisposition. Short stature and skeletal dysmorphisms are almost constant and several studies hypothesized a role for the RAS pathway in regulating bone metabolism. In this study, we investigated the bone quality assessed by phalangeal quantitative ultrasound (QUS) and the metabolic bone profiling in a group of patients with NS, to determine whether low bone mineralization is primary or secondary to NS characteristics. Thirty-five patients were enrolled, including 20 males (55.6%) and 15 females (44.5%) aged 1.0-17.8 years (mean 6.4 ± 4.5, median 4.9 years). Each patients was submitted to clinical examination, estimation of the bone age, laboratory assays, and QUS assessment. Twenty-five percent of the cohort shows reduced QUS values for their age based on bone transmission time. Bone measurement were adjusted for multiple factors frequently observed in NS patients, such as growth retardation, delayed bone age, retarded puberty, and reduced body mass index, potentially affecting bone quality or its appraisal. In spite of the correction attempts, QUS measurement indicates that bone impairment persists in nearly 15% of the cohort studied. Our results indicate that bone impairment in NS is likely primary and not secondary to any of the phenotypic traits of NS, nor consistent with metabolic disturbances. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

How are European birth-cohort studies engaging and consulting with young cohort members?

PubMed

Lucas, Patricia J; Allnock, Debra; Jessiman, Tricia

2013-04-11

Birth cohort studies, where parents consent for their child to be enrolled in a longitudinal study prior to or soon after birth, are a powerful study design in epidemiology and developmental research. Participation often continues into adulthood. Where participants are enrolled as infants, provision should be made for consent, consultation and involvement in study design as they age. This study aims to audit and describe the extent and types of consultation and engagement currently used in birth cohorts in Europe. Seventy study groups (representing 84 cohorts) were contacted to ask about their practice in engaging and involving study members. Information was gathered from study websites and publications, 15 cohorts provided additional information via email and 17 cohorts were interviewed over the phone. The cohorts identified confirm the growth of this study design, with more than half beginning since 1990, and 4 since 2011. Most studies maintain a website open to the general public, although many are written for the scientific community only. Five studies have web pages specifically for young cohort members and one study provides a dedicated page for fathers. Cohorts send newsletters, cards, and summaries of findings to participants to stay in touch. Six cohorts use Facebook for this purpose. Five cohorts provide feedback opportunities for participants after completing a round of data collection. We know of just 8 cohorts who have a mechanism for consulting with parents and 3 a mechanism for consulting with young people themselves, although these were 'one off' consultations for some groups. Barriers to further consultation with cohort members were: concerns about impact on quality of research, ethical constraints, resource limitations, lack of importance, and previous adverse experiences. Although the children in some of the cohorts are still young (born in the last 10 years) many are old enough to include some element of consultation. Barriers to greater participation identified here have been overcome in some cohorts and in other fields. Within the scope of their funding and resources, birth cohort studies should consider ways in which they could increase engagement, consultation, and co-production with research participants.

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

PubMed

Keogh, Ruth H; White, Ian R

2013-10-15

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

Participant profiles according to recruitment source in a large Web-based prospective study: experience from the Nutrinet-Santé study.

PubMed

Kesse-Guyot, Emmanuelle; Andreeva, Valentina; Castetbon, Katia; Vernay, Michel; Touvier, Mathilde; Méjean, Caroline; Julia, Chantal; Galan, Pilar; Hercberg, Serge

2013-09-13

Interest in Internet-based epidemiologic research is growing given the logistic and cost advantages. Cohort recruitment to maximally diversify the sociodemographic profiles of participants, however, remains a contentious issue. The aim of the study was to characterize the sociodemographic profiles according to the recruitment mode of adult volunteers enrolled in a Web-based cohort. The French NutriNet-Santé Web-based cohort was launched in 2009. Recruitment is ongoing and largely relies on recurrent multimedia campaigns. One month after enrollment, participants are asked how they learned about the study (eg, general newscast or a health program on television, radio newscast, newspaper articles, Internet, personal advice, leaflet/flyers) The sociodemographic profiles of participants recruited through operative communication channels (radio, print media, Internet, advice) were compared with the profiles of those informed through television by using polytomous logistic regression. Among the 88,238 participants enrolled through the end of 2011, 30,401 (34.45%), 16,751 (18.98%), and 14,309 (16.22%) learned about the study from television, Internet, and radio newscasts, respectively. Sociodemographic profiles were various, with 14,541 (16.5%) aged ≥60 years, 20,166 (22.9%) aged <30 years, 27,766 (32.1%) without postsecondary education, 15,397 (19.7%) with household income <€1200/month, and 8258 (10.6%) with household income €3700/month. Compared to employed individuals, unemployed and retired participants were less likely to be informed about the study through other sources than through television (adjusted ORs 0.56-0.83, P<.001). Participants reporting up to secondary education were also less likely to have learned about the study through radio newscasts, newspaper articles, Internet, and advice than through television (adjusted ORs 0.60-0.77, P<.001). Television broadcasts appear to permit the recruitment of e-cohort participants with diverse sociodemographic backgrounds, including socioeconomically disadvantaged individuals who are usually difficult to reach and retain in long-term epidemiologic studies. These findings could inform future Web-based studies regarding the development of promising targeted or general population recruitment strategies.

Typhoid fever in young children in Bangladesh: clinical findings, antibiotic susceptibility pattern and immune responses.

PubMed

Khanam, Farhana; Sayeed, Md Abu; Choudhury, Feroza Kaneez; Sheikh, Alaullah; Ahmed, Dilruba; Goswami, Doli; Hossain, Md Lokman; Brooks, Abdullah; Calderwood, Stephen B; Charles, Richelle C; Cravioto, Alejandro; Ryan, Edward T; Qadri, Firdausi

2015-04-01

Children bear a large burden of typhoid fever caused by Salmonella enterica serotype Typhi (S. Typhi) in endemic areas. However, immune responses and clinical findings in children are not well defined. Here, we describe clinical and immunological characteristics of young children with S. Typhi bacteremia, and antimicrobial susceptibility patterns of isolated strains. As a marker of recent infection, we have previously characterized antibody-in-lymphocyte secretion (TPTest) during acute typhoid fever in adults. We similarly assessed membrane preparation (MP) IgA responses in young children at clinical presentation, and then 7-10 days and 21-28 days later. We also assessed plasma IgA, IgG and IgM responses and T cell proliferation responses to MP at these time points. We compared responses in young children (1-5 years) with those seen in older children (6-17 years), adults (18-59 years), and age-matched healthy controls. We found that, compared to age-matched controls patients in all age cohorts had significantly more MP-IgA responses in lymphocyte secretion at clinical presentation, and the values fell in all groups by late convalescence. Similarly, plasma IgA responses in patients were elevated at presentation compared to controls, with acute and convalescent IgA and IgG responses being highest in adults. T cell proliferative responses increased in all age cohorts by late convalescence. Clinical characteristics were similar in all age cohorts, although younger children were more likely to present with loss of appetite, less likely to complain of headache compared to older cohorts, and adults were more likely to have ingested antibiotics. Multi-drug resistant strains were present in approximately 15% of each age cohort, and 97% strains had resistance to nalidixic acid. This study demonstrates that S. Typhi bacteremia is associated with comparable clinical courses, immunologic responses in various age cohorts, including in young children, and that TPTest can be used as marker of recent typhoid fever, even in young children.

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.

Sequential cohort design applying propensity score matching to analyze the comparative effectiveness of atorvastatin and simvastatin in preventing cardiovascular events.

PubMed

Helin-Salmivaara, Arja; Lavikainen, Piia; Aarnio, Emma; Huupponen, Risto; Korhonen, Maarit Jaana

2014-01-01

Sequential cohort design (SCD) applying matching for propensity scores (PS) in accrual periods has been proposed to mitigate bias caused by channeling when calendar time is a proxy for strong confounders. We studied the channeling of patients according to atorvastatin and simvastatin initiation in Finland, starting from the market introduction of atorvastatin in 1998, and explored the SCD PS approach to analyzing the comparative effectiveness of atorvastatin versus simvastatin in the prevention of cardiovascular events (CVE). Initiators of atorvastatin or simvastatin use in the 45-75-year age range in 1998-2006 were characterized by their propensity of receiving atorvastatin over simvastatin, as estimated for 17 six-month periods. Atorvastatin (10 mg) and simvastatin (20 mg) initiators were matched 1∶1 on the PS, as estimated for the whole cohort and within each period. Cox regression models were fitted conventionally, and also for the PS matched cohort and the periodically PS matched cohort, to estimate the hazard ratios (HR) for CVEs. Atorvastatin (10 mg) was associated with a 11%-12% lower incidence of CVE in comparison with simvastatin (20 mg). The HR estimates were the same for a conventional Cox model (0.88, 95% confidence interval 0.85-0.91), for the analysis in which the PS was used to match across all periods and the Cox model was adjusted for strong confounders (0.89, 0.85-0.92), and for the analysis in which PS matching was applied within sequential periods (0.88, 0.84-0.92). The HR from a traditional PS matched analysis was 0.80 (0.77-0.83). The SCD PS approach produced effect estimates similar to those obtained in matching for PS within the whole cohort and adjusting the outcome model for strong confounders, but at the cost of efficiency. A traditional PS matched analysis without further adjustment in the outcome model produced estimates further away from unity.

Measles vaccination improves the equity of health outcomes: evidence from Bangladesh.

PubMed

Bishai, David; Koenig, Michael; Ali Khan, Mehrab

2003-05-01

This paper asks whether measles vaccination can reduce socioeconomic differentials in under five mortality rates (U5MR) in a setting characterized by extreme poverty and high levels of childhood mortality. Longitudinal cohort study based on quasi experimental design. Data come from the phased introduction of a measles vaccine intervention in Matlab, Bangladesh in 1982. There were 16 270 Bangladeshi children aged 9-60 months. The intervention cohort received measles vaccine. Socioeconomic differentials in U5MR between the lowest and highest socioeconomic status (SES) quintiles in a cohort of 8135 vaccinated children and a cohort of unvaccinated age matched controls. Mantel-Haenszel rate ratios for the lowest to highest SES quintile were computed. SES was measured by factor analysis of maternal schooling, land holdings, dwelling size, and number of rooms. The U5MR ratio of lowest SES to highest was 2.27 (95% CI=1.62-3.19) in the unvaccinated population and 1.42 (95%CI=0.94-2.15) in the vaccinated population. The difference between unvaccinated and vaccinated U5MR ratios was statistically significant (p<0.10) and robust across alternative measures of SES. Children from the poorest quintile were more than twice as likely to die as those from the least quintile in the absence of measles vaccination. Universal distribution of measles vaccination largely nullified SES related mortality differentials within a high mortality population of children. Copyright 2002 John Wiley & Sons, Ltd.

Characterization of Intestinal Microbiota in Ulcerative Colitis Patients with and without Primary Sclerosing Cholangitis.

PubMed

Kevans, D; Tyler, A D; Holm, K; Jørgensen, K K; Vatn, M H; Karlsen, T H; Kaplan, G G; Eksteen, B; Gevers, D; Hov, J R; Silverberg, M S

2016-03-01

There is an unexplained association between ulcerative colitis [UC] and primary sclerosing cholangitis [PSC], with the intestinal microbiota implicated as an important factor. The study aim was to compare the structure of the intestinal microbiota of patients with UC with and without PSC. UC patients with PSC [PSC-UC] and without PSC [UC] were identified from biobanks at Oslo University Hospital, Foothills Hospital Calgary and Mount Sinai Hospital Toronto. Microbial DNA was extracted from colonic tissue and sequencing performed of the V4 region of the 16S rRNA gene on Illumina MiSeq. Sequences were assigned to operational taxonomic units [OTUs] using Quantitative Insights Into Microbial Ecology [QIIME]. Microbial alpha diversity, beta diversity, and relative abundance were compared between PSC-UC and UC phenotypes. In all, 31 PSC-UC patients and 56 UC patients were included. Principal coordinate analysis [PCoA] demonstrated that city of sample collection was the strongest determinant of taxonomic profile. In the Oslo cohort, Chao 1 index was modestly decreased in PSC-UC compared with UC [p = 0.04] but did not differ significantly in the Calgary cohort. No clustering by PSC phenotype was observed using beta diversity measures. For multiple microbial genera there were nominally significant differences between UC and PSC-UC, but results were not robust to false-discovery rate correction. No strong PSC-specific microbial associations in UC patients consistent across different cohorts were identified. Recruitment centre had a strong effect on microbial composition. Future studies should include larger cohorts to increase power and the ability to control for confounding factors. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Prevalence of Novel MAGED2 Mutations in Antenatal Bartter Syndrome.

PubMed

Legrand, Anne; Treard, Cyrielle; Roncelin, Isabelle; Dreux, Sophie; Bertholet-Thomas, Aurélia; Broux, Françoise; Bruno, Daniele; Decramer, Stéphane; Deschenes, Georges; Djeddi, Djamal; Guigonis, Vincent; Jay, Nadine; Khalifeh, Tackwa; Llanas, Brigitte; Morin, Denis; Morin, Gilles; Nobili, François; Pietrement, Christine; Ryckewaert, Amélie; Salomon, Rémi; Vrillon, Isabelle; Blanchard, Anne; Vargas-Poussou, Rosa

2018-02-07

Mutations in the MAGED2 gene, located on the X chromosome, have been recently detected in males with a transient form of antenatal Bartter syndrome or with idiopathic polyhydramnios. The aim of this study is to analyze the proportion of the population with mutations in this gene in a French cohort of patients with antenatal Bartter syndrome. The French cohort of patients with antenatal Bartter syndrome encompasses 171 families. Mutations in genes responsible for types 1-4 have been detected in 75% of cases. In patients without identified genetic cause ( n =42), transient antenatal Bartter syndrome was reported in 12 cases. We analyzed the MAGED2 gene in the entire cohort of negative cases by Sanger sequencing and retrospectively collected clinical data regarding pregnancy as well as the postnatal outcome for positive cases. We detected mutations in MAGED2 in 17 patients, including the 12 with transient antenatal Bartter syndrome, from 16 families. Fifteen different mutations were detected (one whole deletion, three frameshift, three splicing, three nonsense, two inframe deletions, and three missense); 13 of these mutations had not been previously described. Interestingly, two patients are females; in one of these patients our data are consistent with selective inactivation of chromosome X explaining the severity. The phenotypic presentation in our patients was variable and less severe than that of the originally described cases. MAGED2 mutations explained 9% of cases of antenatal Bartter syndrome in a French cohort, and accounted for 38% of patients without other characterized mutations and for 44% of male probands of negative cases. Our study confirmed previously published data and showed that females can be affected. As a result, this gene must be included in the screening of the most severe clinical form of Bartter syndrome. Copyright © 2018 by the American Society of Nephrology.

Genetic and serum biomarker evidence for a relationship between TNFα and PTSD in Vietnam war combat veterans.

PubMed

Bruenig, Dagmar; Mehta, Divya; Morris, Charles P; Harvey, Wendy; Lawford, Bruce; Young, Ross McD; Voisey, Joanne

2017-04-01

Posttraumatic stress disorder (PTSD) is associated with increased inflammation and comorbid medical conditions. However, study findings for individual inflammatory marker levels have been inconsistent. Some research suggests that resilience may play a role in decreased inflammation. A polymorphism in the promoter region of the tumor necrosis factor α gene (TNFα), TNFA -308 (rs1800629) is associated with psychiatric illness but its role in PTSD is yet to be elucidated. This study investigates a key inflammatory marker, TNFα, for its role in PTSD severity. In a cohort of trauma-exposed Vietnam War veterans (n=299; 159 cases, 140 controls) TNF α serum levels and TNFα polymorphism rs1800629 were correlated with PTSD severity and resilience scores. The polymorphism was associated with PTSD severity (p=0.045). There were significant group differences between cases and controls with regards to serum TNFα levels (p=0.036). Significant correlations were found between PTSD severity and elevated TNFα levels (r=0.153; p=0.009), and between resilience and decreased TNFα levels at a trend level (p=0.08) across the entire cohort. These relationships were non-significant after controlling for covariates. In the PTSD diagnostic group, a correlation of TNFα and PTSD severity was observed on a trend level (p=0.06), the relationship between TNFα and resilience remained non-significant. To our knowledge, this is the first time rs1800629 has been investigated in PTSD contributing to a growing body of literature that identifies the GG as a risk genotype for psychiatric disorders in Caucasian cohorts. However, more research is needed to replicate our results in larger, equally well-characterized cohorts. The relationship between serum TNFα levels and PTSD severity and resilience requires further investigation. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

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.

Sclerostin antibody treatment improves the bone phenotype of Crtap−/− mice, a model of recessive Osteogenesis Imperfecta

PubMed Central

Grafe, Ingo; Alexander, Stefanie; Yang, Tao; Lietman, Caressa; Homan, Erica P; Munivez, Elda; Chen, Yuqing; Jiang, Ming Ming; Bertin, Terry; Dawson, Brian; Asuncion, Franklin; Ke, Hua Zhu; Ominsky, Michael S; Lee, Brendan

2016-01-01

Osteogenesis Imperfecta (OI) is characterized by low bone mass, poor bone quality and fractures. Standard treatment for OI patients is limited to bisphosphonates, which only incompletely correct the bone phenotype, and seem to be less effective in adults. Sclerostin neutralizing antibodies (Scl-Ab) have been shown to be beneficial in animal models of osteoporosis, and dominant OI resulting from mutations in the genes encoding type I collagen. However, Scl-Ab treatment has not been studied in models of recessive OI. Cartilage associated protein (CRTAP) is involved in posttranslational type I collagen modification, and its loss of function results in recessive OI. In this study, we treated 1 and 6 week old Crtap−/− mice with Scl-Ab for 6 weeks (25 mg/kg, s.c., twice per week), to determine the effects on the bone phenotype in models of “pediatric” and “young adult” recessive OI. Vehicle treated Crtap−/− and wildtype (WT) mice served as controls. Compared with control Crtap−/− mice, microCT analyses showed significant increases in bone volume and improved trabecular microarchitecture in Scl-Ab treated Crtap−/− mice in both age cohorts, in both vertebrae and femurs. Additionally, Scl-Ab improved femoral cortical parameters in both age cohorts. Biomechanical testing showed that Scl-Ab improved parameters of whole bone strength in Crtap−/− mice, with more robust effects in the week 6–12 cohort, but did not affect the increased bone brittleness. Additionally, Scl-Ab normalized the increased osteoclast numbers, stimulated bone formation rate (week 6–12 cohort only), but did not affect osteocyte density. Overall, our findings suggest that Scl-Ab treatment may be beneficial in the treatment of recessive OI caused by defects in collagen post-translational modification. PMID:26716893

Vitamin A and D Deficiencies Associated With Incident Tuberculosis in HIV-Infected Patients Initiating Antiretroviral Therapy in Multinational Case-Cohort Study.

PubMed

Tenforde, Mark W; Yadav, Ashish; Dowdy, David W; Gupte, Nikhil; Shivakoti, Rupak; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Santos, Breno; Poongulali, Selvamuthu; Tripathy, Srikanth; Riviere, Cynthia; Berendes, Sima; Lama, Javier R; Cardoso, Sandra W; Sugandhavesa, Patcharaphan; Christian, Parul; Semba, Richard D; Campbell, Thomas B; Gupta, Amita

2017-07-01

Numerous micronutrients have immunomodulatory roles that may influence risk of tuberculosis (TB), but the association between baseline micronutrient deficiencies and incident TB after antiretroviral therapy (ART) initiation in HIV-infected individuals is not well characterized. We conducted a case-cohort study (n = 332) within a randomized trial comparing 3 ART regimens in 1571 HIV treatment-naive adults from 9 countries. A subcohort of 30 patients was randomly selected from each country (n = 270). Cases (n = 77; main cohort = 62, random subcohort = 15) included patients diagnosed with TB by 96 weeks post-ART initiation. We determined pretreatment concentrations of vitamin A, carotenoids, vitamin B6, vitamin B12, vitamin D, vitamin E, and selenium. We measured associations between pretreatment micronutrient deficiencies and incident TB using Breslow-weighted Cox regression models. Median pretreatment CD4 T-cell count was 170 cells/mm; 47.3% were women; and 53.6% Black. In multivariable models after adjusting for age, sex, country, treatment arm, previous TB, baseline CD4 count, HIV viral load, body mass index, and C-reactive protein, pretreatment deficiency in vitamin A (adjusted hazard ratio, aHR 5.33, 95% confidence interval, CI: 1.54 to 18.43) and vitamin D (aHR 3.66, 95% CI: 1.16 to 11.51) were associated with TB post-ART. In a diverse cohort of HIV-infected adults from predominantly low- and middle-income countries, deficiencies in vitamin A and vitamin D at ART initiation were independently associated with increased risk of incident TB in the ensuing 96 weeks. Vitamin A and D may be important modifiable risk factors for TB in high-risk HIV-infected patients starting ART in resource-limited highly-TB-endemic settings.

Decomposing Black-White Disparities in Heart Disease Mortality in the United States, 1973–2010: An Age-Period-Cohort Analysis

PubMed Central

Kramer, Michael R.; Valderrama, Amy L.; Casper, Michele L.

2015-01-01

Against the backdrop of late 20th century declines in heart disease mortality in the United States, race-specific rates diverged because of slower declines among blacks compared with whites. To characterize the temporal dynamics of emerging black-white racial disparities in heart disease mortality, we decomposed race-sex–specific trends in an age-period-cohort (APC) analysis of US mortality data for all diseases of the heart among adults aged ≥35 years from 1973 to 2010. The black-white gap was largest among adults aged 35–59 years (rate ratios ranged from 1.2 to 2.7 for men and from 2.3 to 4.0 for women) and widened with successive birth cohorts, particularly for men. APC model estimates suggested strong independent trends across generations (“cohort effects”) but only modest period changes. Among men, cohort-specific black-white racial differences emerged in the 1920–1960 birth cohorts. The apparent strength of the cohort trends raises questions about life-course inequalities in the social and health environments experienced by blacks and whites which could have affected their biomedical and behavioral risk factors for heart disease. The APC results suggest that the genesis of racial disparities is neither static nor restricted to a single time scale such as age or period, and they support the importance of equity in life-course exposures for reducing racial disparities in heart disease. PMID:26199382

Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer.

PubMed

Yu, Ke-Da; Jiang, Yi-Zhou; Hao, Shuang; Shao, Zhi-Ming

2015-10-05

The clinical significance of progesterone receptor (PgR) expression in estrogen receptor-negative (ER-) breast cancer is controversial. Herein, we systemically investigate the clinicopathologic features, molecular essence, and endocrine responsiveness of ER-/PgR+/HER2- phenotype. Four study cohorts were included. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n = 67,932) and Fudan University Shanghai Cancer Center (n = 2,338), respectively, for clinicopathologic and survival analysis. The third and fourth cohorts were from two independent publicly available microarray datasets including 837 operable cases and 483 cases undergoing neoadjuvant chemotherapy, respectively, for clinicopathologic and gene-expression analysis. Characterized genes defining subgroups within the ER-/PgR+/HER2- phenotype were determined and further validated. Clinicopathologic features and survival outcomes of the ER-/PgR+ phenotype fell in between the ER+/PgR+ and ER-/PgR- phenotypes, but were more similar to ER-/PgR-. Among the ER-/PgR+ phenotype, 30% (95% confidence interval [CI] 17-42%, pooled by a fixed-effects method) were luminal-like and 59% (95% CI 45-72%, pooled by a fixed-effects method) were basal-like. We further refined the characterized genes for subtypes within the ER-/PgR+ phenotype and developed an immunohistochemistry-based method that could determine the molecular essence of ER-/PgR+ using three markers, TFF1, CK5, and EGFR. Either PAM50-defined or immunohistochemistry-defined basal-like ER-/PgR+ cases have a lower endocrine therapy sensitivity score compared with luminal-like ER-/PgR+ cases (P <0.0001 by Mann-Whitney test for each study set and P <0.0001 for pooled standardized mean difference in meta-analysis). Immunohistochemistry-defined basal-like ER-/PgR+ cases might not benefit from adjuvant endocrine therapy (log-rank P = 0.61 for sufficient versus insufficient endocrine therapy). The majority of ER-/PgR+/HER2- phenotype breast cancers are basal-like and associated with a lower endocrine therapy sensitivity score. Additional studies are needed to validate these findings.

Clinical spectrum of primary hyperoxaluria type 1: Experience of a tertiary center.

PubMed

Soliman, Neveen A; Nabhan, Marwa M; Abdelrahman, Safaa M; Abdelaziz, Hanan; Helmy, Rasha; Ghanim, Khaled; Bazaraa, Hafez M; Badr, Ahmed M; Tolba, Omar A; Kotb, Magd A; Eweeda, Khaled M; Fayez, Alaa

2017-05-01

Primary hyperoxalurias are rare inborn errors of metabolism resulting in increased endogenous production of oxalate that leads to excessive urinary oxalate excretion. Diagnosis of primary hyperoxaluria type 1 (PH1) is a challenging issue and depends on diverse diagnostic tools including biochemical analysis of urine, stone analysis, renal biopsy, genetic studies and in some cases liver biopsy for enzyme assay. We characterized the clinical presentation as well as renal and extrarenal phenotypes in PH1 patients. This descriptive cohort study included patients with presumable PH1 presenting with nephrolithiasis and/or nephrocalcinosis (NC). Precise clinical characterization of renal phenotype as well as systemic involvement is reported. AGXT mutational analysis was performed to confirm the diagnosis of PH1. The study cohort included 26 patients with presumable PH1 with male to female ratio of 1.4:1. The median age at time of diagnosis was 6 years, nevertheless the median age at initial symptoms was 3 years. Thirteen patients (50%) were diagnosed before the age of 5 years. Two patients had no symptoms and were diagnosed while screening siblings of index patients. Seventeen patients (65.4%) had reached end-stage renal disease (ESRD): 6/17 (35.3%) during infancy, 4/17 (23.5%) in early childhood and 7/17 (41.29%) in late childhood. Two patients (7.7%) had clinically manifest extra renal (retina, heart, bone, soft tissue) involvement. Mutational analysis of AGXT gene confirmed the diagnosis of PH1 in 15 out of 19 patients (79%) where analysis had been performed. Fifty percent of patients with maintained renal functions had projected 10 years renal survival. PH1 is a heterogeneous disease with wide spectrum of clinical, imaging and functional presentation. More than two-thirds of patients presented prior to the age of 5 years; half of them with the stormy course of infantile PH1. ESRD was the commonest presenting manifestation in two-thirds of our cohort. Copyright © 2016 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.

Patterns of Care and Treatment Target Success among Persons with Type 2 Diabetes Mellitus in Dubai: A Retrospective Cohort Study.

PubMed

Osenenko, Katherine M; Szabo, Shelagh M; Qatami, Lara; Korenblat Donato, Bonnie M; Al Madani, Abdulrazzak Ali; Al Awadi, Fatheya Fardallah; Al-Ansari, Jaber; Maclean, Ross; Levy, Adrian R

2015-09-01

Despite the high prevalence of type 2 diabetes mellitus (T2DM), few data exist describing its management in Dubai. This study characterized the treatment and estimated levels of glycemic, lipid, and blood pressure control among a sample with T2DM at a large Dubai Hospital. This retrospective cohort study systematically sampled charts from adults seeking care for T2DM from October 2009 to March 2010 until the target (N = 250) was reached. Data on patient characteristics, pharmacotherapy, complications, and laboratory testing were abstracted until September 2011. The frequency of treatments and modifications over the period was calculated, and measures of glycosylated hemoglobin A 1c , low-density lipoprotein, and blood pressure control were compared with guideline targets. Frequencies of complications were compared according to treatment type. One-third of the cohort comprised men, and the mean age was 58 years. At enrolment, the mean time from T2DM diagnosis was nearly 15 years and 74% had received insulin. During the study period, the most common regimens were insulin + oral combinations (55%) and oral combination therapy (39%). Overall, 67% received any insulin therapy during the study; and by study end, 78% had received insulin at any time. At the most recent assessment, guideline targets for glycosylated hemoglobin A 1c , blood pressure, and low-density lipoprotein were met by 23%, 29%, and 71%, respectively. Complications were more frequent among those treated with combination or insulin therapies. This study provides baseline data from Dubai for future comparisons of the effectiveness of new treatments, and to better understand the humanistic and economic burden of T2DM and its complications. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Integrated Molecular Characterization of Uterine Carcinosarcoma.

PubMed

Cherniack, Andrew D; Shen, Hui; Walter, Vonn; Stewart, Chip; Murray, Bradley A; Bowlby, Reanne; Hu, Xin; Ling, Shiyun; Soslow, Robert A; Broaddus, Russell R; Zuna, Rosemary E; Robertson, Gordon; Laird, Peter W; Kucherlapati, Raju; Mills, Gordon B; Weinstein, John N; Zhang, Jiashan; Akbani, Rehan; Levine, Douglas A

2017-03-13

We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters. The range of EMT scores in UCS was the largest among all tumor types studied via The Cancer Genome Atlas. UCSs shared proteomic features with gynecologic carcinomas and sarcomas with intermediate EMT features. Multiple somatic mutations and copy-number alterations in genes that are therapeutic targets were identified. Copyright © 2017 Elsevier Inc. All rights reserved.

A comparison of Cox and logistic regression for use in genome-wide association studies of cohort and case-cohort design.

PubMed

Staley, James R; Jones, Edmund; Kaptoge, Stephen; Butterworth, Adam S; Sweeting, Michael J; Wood, Angela M; Howson, Joanna M M

2017-06-01

Logistic regression is often used instead of Cox regression to analyse genome-wide association studies (GWAS) of single-nucleotide polymorphisms (SNPs) and disease outcomes with cohort and case-cohort designs, as it is less computationally expensive. Although Cox and logistic regression models have been compared previously in cohort studies, this work does not completely cover the GWAS setting nor extend to the case-cohort study design. Here, we evaluated Cox and logistic regression applied to cohort and case-cohort genetic association studies using simulated data and genetic data from the EPIC-CVD study. In the cohort setting, there was a modest improvement in power to detect SNP-disease associations using Cox regression compared with logistic regression, which increased as the disease incidence increased. In contrast, logistic regression had more power than (Prentice weighted) Cox regression in the case-cohort setting. Logistic regression yielded inflated effect estimates (assuming the hazard ratio is the underlying measure of association) for both study designs, especially for SNPs with greater effect on disease. Given logistic regression is substantially more computationally efficient than Cox regression in both settings, we propose a two-step approach to GWAS in cohort and case-cohort studies. First to analyse all SNPs with logistic regression to identify associated variants below a pre-defined P-value threshold, and second to fit Cox regression (appropriately weighted in case-cohort studies) to those identified SNPs to ensure accurate estimation of association with disease.

Replicable in vivo physiological and behavioral phenotypes of the Shank3B null mutant mouse model of autism.

PubMed

Dhamne, Sameer C; Silverman, Jill L; Super, Chloe E; Lammers, Stephen H T; Hameed, Mustafa Q; Modi, Meera E; Copping, Nycole A; Pride, Michael C; Smith, Daniel G; Rotenberg, Alexander; Crawley, Jacqueline N; Sahin, Mustafa

2017-01-01

Autism spectrum disorder (ASD) is a clinically and biologically heterogeneous condition characterized by social, repetitive, and sensory behavioral abnormalities. No treatments are approved for the core diagnostic symptoms of ASD. To enable the earliest stages of therapeutic discovery and development for ASD, robust and reproducible behavioral phenotypes and biological markers are essential to establish in preclinical animal models. The goal of this study was to identify electroencephalographic (EEG) and behavioral phenotypes that are replicable between independent cohorts in a mouse model of ASD. The larger goal of our strategy is to empower the preclinical biomedical ASD research field by generating robust and reproducible behavioral and physiological phenotypes in animal models of ASD, for the characterization of mechanistic underpinnings of ASD-relevant phenotypes, and to ensure reliability for the discovery of novel therapeutics. Genetic disruption of the SHANK3 gene, a scaffolding protein involved in the stability of the postsynaptic density in excitatory synapses, is thought to be responsible for a relatively large number of cases of ASD. Therefore, we have thoroughly characterized the robustness of ASD-relevant behavioral phenotypes in two cohorts, and for the first time quantified translational EEG activity in Shank3B null mutant mice. In vivo physiology and behavioral assays were conducted in two independently bred and tested full cohorts of Shank3B null mutant ( Shank3B KO) and wildtype littermate control (WT) mice. EEG was recorded via wireless implanted telemeters for 7 days of baseline followed by 20 min of recording following pentylenetetrazol (PTZ) challenge. Behaviors relevant to the diagnostic and associated symptoms of ASD were tested on a battery of established behavioral tests. Assays were designed to reproduce and expand on the original behavioral characterization of Shank3B KO mice. Two or more corroborative tests were conducted within each behavioral domain, including social, repetitive, cognitive, anxiety-related, sensory, and motor categories of assays. Relative to WT mice, Shank3B KO mice displayed a dramatic resistance to PTZ seizure induction and an enhancement of gamma band oscillatory EEG activity indicative of enhanced inhibitory tone. These findings replicated in two separate cohorts. Behaviorally, Shank3B KO mice exhibited repetitive grooming, deficits in aspects of reciprocal social interactions and vocalizations, and reduced open field activity, as well as variable deficits in sensory responses, anxiety-related behaviors, learning and memory. Robust animal models and quantitative, replicable biomarkers of neural dysfunction are needed to decrease risk and enable successful drug discovery and development for ASD and other neurodevelopmental disorders. Complementary to the replicated behavioral phenotypes of the Shank3B mutant mouse is the new identification of a robust, translational in vivo neurophysiological phenotype. Our findings provide strong evidence for robustness and replicability of key translational phenotypes in Shank3B mutant mice and support the usefulness of this mouse model of ASD for therapeutic discovery.

Acute alcohol response phenotype in heavy social drinkers is robust and reproducible.

PubMed

Roche, Daniel J O; Palmeri, Michael D; King, Andrea C

2014-03-01

In 3 previously published works (Brumback et al., 2007, Drug Alcohol Depend 91:10-17; King et al., 2011a, Arch Gen Psychiatry 68:389-399; Roche and King, 2010, Psychopharmacology (Berl) 212:33-44), our group characterized acute alcohol responses in a large group of young, heavy binge drinkers (n = 104) across a variety of subjective, eye-tracking, and psychometric performance measures. The primary goal of the current study was to directly replicate prior findings of alcohol response in heavy social drinkers (HD) in a second independent cohort (n = 104) using identical methodology. A secondary goal was to examine the effects of family history (FH) of alcohol use disorders (AUD) on acute alcohol response in both samples. Participants attended 2 randomized laboratory sessions in which they consumed 0.8 g/kg alcohol or a taste-masked placebo. At pre- and post-drink time points, participants completed subjective scales, psychomotor performance and eye-movement tasks, and provided salivary samples for cortisol determination. Results showed that the second cohort of heavy drinkers exhibited a nearly identical pattern of alcohol responses to the original cohort, including sensitivity to alcohol's stimulating and hedonically rewarding effects during the rising breath alcohol content (BrAC) limb, increases in sedation during the declining BrAC limb, a lack of cortisol response, and psychomotor and eye-tracking impairment that was most evident at peak BrAC. The magnitude and temporal pattern of these acute effects of alcohol in the second cohort were similar to the first cohort across all measures, with the exception of 3 eye-movement measures: pro- and antisaccade accuracy and antisaccade velocity. FH of AUD did not affect alcohol response in the first cohort, and this was replicated in the second cohort. In sum, in 2 independent samples, we have demonstrated that HD display a consistent and reliable sensitivity to alcohol's subjective effects and impairment of eye-tracking and psychomotor performance, which is not affected by FH status. This acute alcohol response phenotype in heavy, frequent binge drinkers appears to be robust and reproducible. Copyright © 2013 by the Research Society on Alcoholism.

A cohort study of Chlamydia trachomatis treatment failure in women: a study protocol

PubMed Central

2013-01-01

Background Chlamydia trachomatis is the most commonly diagnosed bacterial sexually transmitted infection in the developed world and diagnosis rates have increased dramatically over the last decade. Repeat infections of chlamydia are very common and may represent re-infection from an untreated partner or treatment failure. The aim of this cohort study is to estimate the proportion of women infected with chlamydia who experience treatment failure after treatment with 1 gram azithromycin. Methods/design This cohort study will follow women diagnosed with chlamydia for up to 56 days post treatment. Women will provide weekly genital specimens for further assay. The primary outcome is the proportion of women who are classified as having treatment failure 28, 42 or 56 days after recruitment. Comprehensive sexual behavior data collection and the detection of Y chromosome DNA and high discriminatory chlamydial genotyping will be used to differentiate between chlamydia re-infection and treatment failure. Azithromycin levels in high-vaginal specimens will be measured using a validated liquid chromatography – tandem mass spectrometry method to assess whether poor azithromycin absorption could be a cause of treatment failure. Chlamydia culture and minimal inhibitory concentrations will be performed to further characterize the chlamydia infections. Discussion Distinguishing between treatment failure and re-infection is important in order to refine treatment recommendations and focus infection control mechanisms. If a large proportion of repeat chlamydia infections are due to antibiotic treatment failure, then international recommendations on chlamydia treatment may need to be re-evaluated. If most are re-infections, then strategies to expedite partner treatment are necessary. PMID:23957327

Effects of Sex and Education on Cognitive Change Over a 27-Year Period in Older Adults: The Rancho Bernardo Study.

PubMed

Reas, Emilie T; Laughlin, Gail A; Bergstrom, Jaclyn; Kritz-Silverstein, Donna; Barrett-Connor, Elizabeth; McEvoy, Linda K

2017-08-01

This study investigated how cognitive function changes with age and whether rates of decline vary by sex or education in a large, homogenous longitudinal cohort characterized by high participation rates, long duration of follow-up, and minimal loss to follow-up. Between 1988 and 2016, 2,225 community-dwelling participants of the Rancho Bernardo Study, aged 31 to 99 years at their initial cognitive assessment, completed neuropsychological testing approximately every 4 years, over a maximum 27-year follow-up. Linear mixed effects regression models defined sex-specific cognitive trajectories, adjusting for education and retest effects. Significant decline across all cognitive domains began around age 65 years and accelerated after age 80 years. Patterns of decline were generally similar between sexes, although men declined more rapidly than women on the global function test. Higher education was associated with slower decline on the tests of executive and global functions. After excluding 517 participants with evidence of cognitive impairment, accelerating decline with age remained for all tests, and women declined more rapidly than men on the executive function test. Accelerating decline with advancing age occurs across multiple cognitive domains in community-dwelling older adults, with few differences in rates of decline between men and women. Higher education may provide some protection against executive and global function decline with age. These findings better characterize normal cognitive aging, a critical prerequisite for identifying individuals at risk for cognitive impairment, and lay the groundwork for future studies of health and behavioral factors that affect age-related decline in this cohort. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women

PubMed Central

Arleevskaya, Marina I.; Shafigullina, Albina Z.; Filina, Yulia V.; Lemerle, Julie; Renaudineau, Yves

2017-01-01

To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further. PMID:29259607

Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women.

PubMed

Arleevskaya, Marina I; Shafigullina, Albina Z; Filina, Yulia V; Lemerle, Julie; Renaudineau, Yves

2017-01-01

To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further.

Comparing older and younger Japanese primiparae: fatigue, depression and biomarkers of stress.

PubMed

Mori, Emi; Maehara, Kunie; Iwata, Hiroko; Sakajo, Akiko; Tsuchiya, Miyako; Ozawa, Harumi; Morita, Akiko; Maekawa, Tomoko; Saeki, Akiko

2015-03-01

This cohort study of primiparae was conducted to answer the following questions: Do older (≧ 35 years) and younger (20-29 years) Japanese primiparous mothers differ when comparing biomarkers of stress and measures of fatigue and depression? Are there changes in fatigue, depression and stress biomarkers when comparing older and younger mothers during the postpartum period? The Postnatal Accumulated Fatigue Scale and the Edinburgh Postnatal Depression Scale were administered in a time-series method four times: shortly after birth and monthly afterwards. Assays to measure biomarkers of stress, urinary 17-ketosteroids, urinary 17-hydroxycorticosteroids and salivary chromogranin-A, were collected shortly after delivery and at 1 month postpartum in both groups and a third time in older mothers at the 4th month. Statistical testing showed very little difference in fatigue, depression or stress biomarkers between older and younger mothers shortly after birth or 1 month later. Accumulated fatigue and depression scores of older mothers were highest 1 month after delivery. Additional cohort studies are required to characterize physical/psychological well-being of older Japanese primiparae. © 2015 Wiley Publishing Asia Pty Ltd.

Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study in the Asia-Pacific Region (MUSIC OS-AP): Design of a multinational, prospective, observational study examining the impact of gastrointestinal events on osteoporosis management in postmenopausal women.

PubMed

Modi, Ankita; Ebeling, Peter R; Lee, Mel S; Min, Yong-Ki; Mithal, Ambrish; Yang, Xiaoqin; Sajjan, Shiva

2015-12-01

The burden of osteoporosis in the Asia-Pacific region is not well characterized. The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study in the Asia-Pacific Region (MUSIC OS-AP) was designed to better understand the association of gastrointestinal events with patient-reported outcomes in postmenopausal women of this region. MUSIC OS-AP is a prospective, multinational, observational cohort study of postmenopausal women ≥ 50 years of age diagnosed with osteoporosis. The study was conducted in five Asia-Pacific countries: Australia, New Zealand, Taiwan, Korea, and India. MUSIC OS-AP has three components: a physician questionnaire, a retrospective chart review, and a prospective cohort study. The physician questionnaire investigated the role of gastrointestinal events in physicians' pharmacologic management of osteoporosis. The retrospective chart review, also completed by physicians, recorded rate of osteoporosis treatment and the types of osteoporosis medications prescribed to osteoporosis patients. The prospective cohort study investigated the associations between gastrointestinal events and patient-reported outcomes among patients taking oral medications for osteoporosis as well as reasons for non-treatment in patients who remained untreated. The prospective cohort study enrolled two groups of patients: untreated, and treated with oral osteoporosis medications. Untreated patients completed only the baseline surveys, providing information on gastrointestinal event rates, quality of life, health care resource use, and reasons for non-treatment. Treated patients, who were either new to osteoporosis medication or continuing an ongoing medication course, completed surveys at baseline and 3, 6, and 12 months post-baseline. The evaluations recorded patient characteristics, gastrointestinal events, health-related and osteoporosis-specific quality of life, health care resource use, medication adherence, and satisfaction with treatment. Physicians at 59 sites completed the physician questionnaire, and data for 300 patients from 26 sites were abstracted for the retrospective chart review. Enrollment and baseline data collection for the prospective cohort study were conducted between July 2013 and August 2014 for 301 untreated and 3287 treated patients, of whom 1416 were new users and 1871 were experienced users of oral osteoporosis medications. The results of MUSIC OS-AP will highlight the association of gastrointestinal events with patient-reported outcomes among postmenopausal women with osteoporosis and elucidate physicians' management of gastrointestinal events among this patient population in the Asia-Pacific region.

Meta-analytic framework for sparse K-means to identify disease subtypes in multiple transcriptomic studies

PubMed Central

Huo, Zhiguang; Ding, Ying; Liu, Silvia; Oesterreich, Steffi; Tseng, George

2016-01-01

Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K-means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups. PMID:27330233

Classification of Clinical Research Study Eligibility Criteria to Support Multi-Stage Cohort Identification Using Clinical Data Repositories.

PubMed

Cimino, James J; Lancaster, William J; Wyatt, Mathew C

2017-01-01

One of the challenges to using electronic health record (EHR) repositories for research is the difficulty mapping study subject eligibility criteria to the query capabilities of the repository. We sought to characterize criteria as "easy" (searchable in a typical repository), "hard" (requiring manual review of the record data), and "impossible" (not typically available in EHR repositories). We obtained 292 criteria from 20 studies available from Clinical Trials.gov and rated them according to our three types, plus a fourth "mixed" type. We had good agreement among three independent reviewers and chose 274 criteria that were characterized by single types for further analysis. The resulting analysis showed typical features of criteria that do and don't map to repositories. We propose that these features be used to guide researchers in specifying eligibility criteria to improve development of enrollment workflow, including the definition of EHR repository queries for self-service or analyst-mediated retrievals.

Meta-analytic framework for sparse K-means to identify disease subtypes in multiple transcriptomic studies.

PubMed

Huo, Zhiguang; Ding, Ying; Liu, Silvia; Oesterreich, Steffi; Tseng, George

Disease phenotyping by omics data has become a popular approach that potentially can lead to better personalized treatment. Identifying disease subtypes via unsupervised machine learning is the first step towards this goal. In this paper, we extend a sparse K -means method towards a meta-analytic framework to identify novel disease subtypes when expression profiles of multiple cohorts are available. The lasso regularization and meta-analysis identify a unique set of gene features for subtype characterization. An additional pattern matching reward function guarantees consistent subtype signatures across studies. The method was evaluated by simulations and leukemia and breast cancer data sets. The identified disease subtypes from meta-analysis were characterized with improved accuracy and stability compared to single study analysis. The breast cancer model was applied to an independent METABRIC dataset and generated improved survival difference between subtypes. These results provide a basis for diagnosis and development of targeted treatments for disease subgroups.

Clinical, Endocrine, and Molecular Genetic Analysis of a Large Cohort of Saudi Arabian Patients with Laron Syndrome.

PubMed

Al-Ashwal, Abdullah A; Al-Sagheir, Afaf; Ramzan, Khushnooda; Al-Owain, Mohammed; Allam, Rabab; Qari, Alya; Al-Numair, Nouf S; Imtiaz, Faiqa

2017-01-01

Laron syndrome (LS) is an autosomal recessive disease characterized by marked short stature and very low serum IGF-1 and IGFBP-3 levels. This study assessed the clinical and endocrine features alongside determining the growth hormone receptor gene (GHR) mutation in Saudi Arabian patients with LS in order to establish whether or not a genotype/phenotype correlation is evident in this large cohort. A total of 40 Saudi Arabian patients with a suspected diagnosis of LS were recruited and subjected to a full clinical and endocrine investigation together with direct sequencing of the coding regions of the GHR gene. GHR mutations were identified in 34 patients from 22 separate nuclear families. All 34 molecularly confirmed patients had the typical clinical and endocrinological manifestations of LS. Eleven different mutations (9 previously unreported) were detected in this cohort of patients, all inherited in an autosomal recessive homozygous form. No genotype/phenotype correlation was apparent. The identification of pathogenic mutations causing LS will be of tremendous use for the molecular diagnosis of patients in Saudi Arabia and the region in general, with respect to prevention of this disease in the forms of future carrier testing, prenatal testing, premarital screening and preimplantation genetic diagnosis. © 2017 S. Karger AG, Basel.

Demographic analysis of arrhenotokous parthenogenesis and bisexual reproduction of Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae).

PubMed

Ding, Tianbo; Chi, Hsin; Gökçe, Ayhan; Gao, Yulin; Zhang, Bin

2018-02-20

Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) is a serious pest that is capable of bisexual and arrhenotokous reproduction. In arrhenotokous reproduction, virgin females initially produce male offspring; later, when their sons are sexually mature, the mothers begin bisexual reproduction by carrying out oedipal mating with their sons. Because a virgin female produces many male offspring before oedipal mating occurs, multiple oedipal mating is common. In this study, we investigated the effect of multiple oedipal mating on the population growth of F. occidentalis by using the age-stage, two-sex life table theory. In the arrhenotokous cohorts, all unfertilized eggs developed into males. In the bisexual cohorts, the offspring sex ratio was significantly female biased with the mean number of female offspring and male offspring being 72.68 and 29.00, respectively. These were the same as the net reproductive rate of female offspring and male offspring. In arrhenotokous cohorts, the number of males available for oedipal mating significantly affected the production of female offspring. The number of female offspring increased as the number of sons available for oedipal mating increased. Correctly characterizing this unique type of reproduction will provide important information for predicting the timing of future outbreaks of F. occidentalis, as well as aiding in formulating successful management strategies against the species.

Individual Data Linkage of Survey Data with Claims Data in Germany—An Overview Based on a Cohort Study

PubMed Central

March, Stefanie

2017-01-01

Research based on health insurance data has a long tradition in Germany. By contrast, data linkage of survey data with such claims data is a relatively new field of research with high potential. Data linkage opens up new opportunities for analyses in the field of health services research and public health. Germany has comprehensive rules and regulations of data protection that have to be followed. Therefore, a written informed consent is needed for individual data linkage. Additionally, the health system is characterized by heterogeneity of health insurance. The lidA-living at work-study is a cohort study on work, age and health, which linked survey data with claims data of a large number of statutory health insurance data. All health insurance funds were contacted, of whom a written consent was given. This paper will give an overview of individual data linkage of survey data with German claims data on the example of the lidA-study results. The challenges and limitations of data linkage will be presented. Despite heterogeneity, such kind of studies is possible with a negligibly small influence of bias. The experience we gain in lidA will be shown and provide important insights for other studies focusing on data linkage. PMID:29232834

Individual Data Linkage of Survey Data with Claims Data in Germany-An Overview Based on a Cohort Study.

PubMed

March, Stefanie

2017-12-09

Research based on health insurance data has a long tradition in Germany. By contrast, data linkage of survey data with such claims data is a relatively new field of research with high potential. Data linkage opens up new opportunities for analyses in the field of health services research and public health. Germany has comprehensive rules and regulations of data protection that have to be followed. Therefore, a written informed consent is needed for individual data linkage. Additionally, the health system is characterized by heterogeneity of health insurance. The lidA-living at work-study is a cohort study on work, age and health, which linked survey data with claims data of a large number of statutory health insurance data. All health insurance funds were contacted, of whom a written consent was given. This paper will give an overview of individual data linkage of survey data with German claims data on the example of the lidA-study results. The challenges and limitations of data linkage will be presented. Despite heterogeneity, such kind of studies is possible with a negligibly small influence of bias. The experience we gain in lidA will be shown and provide important insights for other studies focusing on data linkage.

Diesel engine exhaust and lung cancer: an unproven association.

PubMed Central

Muscat, J E; Wynder, E L

1995-01-01

The risk of lung cancer associated with diesel exhaust has been calculated from 14 case-control or cohort studies. We evaluated the findings from these studies to determine whether there is sufficient evidence to implicate diesel exhaust as a human lung carcinogen. Four studies found increased risks associated with long-term exposure, although two of the four studies were based on the same cohort of railroad workers. Six studies were inconclusive due to missing information on smoking habits, internal inconsistencies, or inadequate characterization of diesel exposure. Four studies found no statistically significant associations. It can be concluded that short-term exposure to diesel engine exhaust (< 20 years) does not have a causative role in human lung cancer. There is statistical but not causal evidence that long-term exposure to diesel exhaust (> 20 years) increases the risk of lung cancer for locomotive engineers, brakemen, and diesel engine mechanics. There is inconsistent evidence on the effects of long-term exposure to diesel exhaust in the trucking industry. There is no evidence for a joint effect of diesel exhaust and cigarette smoking on lung cancer risk. Using common criteria for determining causal associations, the epidemiologic evidence is insufficient to establish diesel engine exhaust as a human lung carcinogen. Images p812-a PMID:7498093

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

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

PubMed

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

2018-01-27

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

A Study of Group Dynamics in Educational Leadership Cohort and Non-Cohort Groups

ERIC Educational Resources Information Center

Greenlee, Bobbie J.; Karanxha, Zorka

2010-01-01

The purpose of this study was to examine group dynamics of educational leadership students in cohorts and make comparisons with the group dynamics characteristics of non-cohort students. Cohorts have emerged as dynamic and adaptive entities with attendant group dynamic processes that shape collective learning and action. Cohort (n=42) and…

Human gut microbiome viewed across age and geography

USDA-ARS?s Scientific Manuscript database

Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, we characterized bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy child...

Sleep characteristics and progression of coronary artery calcification: Results from the Heinz Nixdorf Recall cohort study.

PubMed

Kowall, Bernd; Lehmann, Nils; Mahabadi, Amir-Abbas; Lehnich, Anna-Therese; Moebus, Susanne; Budde, Thomas; Seibel, Rainer; Grönemeyer, Dietrich; Erbel, Raimund; Jöckel, Karl-Heinz; Stang, Andreas

2018-04-01

Sleep characteristics are associated with incident cardiovascular diseases (CVD), but there is a lack of studies on the association between sleep characteristics and incidence/progression of coronary artery calcification (CAC). In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany, CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. In an analysis set of 3043 subjects (age at baseline 45-74 years; 47% men), we fitted logistic and linear regression models to assess associations between self-rated sleep characteristics (nocturnal and total sleep duration; napping; various sleep disorders) and CAC incidence/CAC progression. Progression was measured as 5-year progression factor, as categories of absolute CAC change, and additionally characterized as rapid or slow compared to an extrapolation of baseline CAC values. We observed barely any association between sleep characteristics and CAC progression regardless of the chosen statistical approach; associations between sleep and CAC incidence were slightly larger, e.g., the geometric mean of the 5-year CAC progression factor was 6.8% (95% confidence interval: -9.5; 25.9) larger for ≤5 h, 2.9% (-7.3; 14.3) larger for 5.1-6.9 h and 7.1% (-2.4; 15.7) smaller for ≥7.5 h total sleep compared to 7- <7.5 h total sleep. For subjects with any regular sleep disorder, the geometric mean of the 5-year CAC progression was 3.5% (-4.7; 11.2) smaller compared to subjects without any regular sleep disorder. In this German cohort study, sleep characteristics were barely associated with CAC progression. Copyright © 2018 Elsevier B.V. All rights reserved.

Helicobacter pylori strains from a Nigerian cohort show divergent antibiotic resistance rates and a uniform pathogenicity profile

PubMed Central

Harrison, Ute; Fowora, Muinah A.; Seriki, Abiodun T.; Loell, Eva; Mueller, Susanna; Ugo-Ijeh, Margaret; Onyekwere, Charles A.; Lesi, Olufunmilayo A.; Otegbayo, Jesse A.; Akere, Adegboyega; Ndububa, Dennis A.; Adekanle, Olusegun; Anomneze, Ebere; Abdulkareem, Fatimah B.; Adeleye, Isaac A.; Crispin, Alexander; Rieder, Gabriele; Fischer, Wolfgang; Smith, Stella I.; Haas, Rainer

2017-01-01

Antibiotic resistance in Helicobacter pylori is a factor preventing its successful eradication. Particularly in developing countries, resistance against commonly used antibiotics is widespread. Here, we present an epidemiological study from Nigeria with 111 isolates. We analyzed the associated disease outcome, and performed a detailed characterization of these isolated strains with respect to their antibiotic susceptibility and their virulence characteristics. Furthermore, statistical analysis was performed on microbiological data as well as patient information and the results of the gastroenterological examination. We found that the variability concerning the production of virulence factors between strains was minimal, with 96.4% of isolates being CagA-positive and 92.8% producing detectable VacA levels. In addition, high frequency of bacterial resistance was observed for metronidazole (99.1%), followed by amoxicillin (33.3%), clarithromycin (14.4%) and tetracycline (4.5%). In conclusion, this study indicated that the infection rate of H. pylori infection within the cohort in the present study was surprisingly low (36.6%). Furthermore, an average gastric pathology was observed by histological grading and bacterial isolates showed a uniform pathogenicity profile while indicating divergent antibiotic resistance rates. PMID:28463973

Disease outcome of inflammatory bowel disease patients: general outline of a Europe-wide population-based 10-year clinical follow-up study.

PubMed

Wolters, Frank L; Russel, Maurice G; Sijbrandij, Jildou; Schouten, Leo J; Odes, Selwyn; Riis, Lene; Munkholm, Pia; Langholz, Ebbe; Bodini, Paolo; O'Morain, Colm; Katsanos, Kostas; Tsianos, Epameinondas; Vermeire, Severine; Van Zeijl, Gilbert; Limonard, Charles; Hoie, Ole; Vatn, Morten; Moum, Bjørn; Stockbrügger, Reinhold W

2006-01-01

To give a general outline of a 10-year clinical follow-up study of a population-based European cohort of inflammatory bowel disease (IBD) patients and to present the first results in terms of clinical outcome parameters and risk factors. A population-based cohort of newly, prospectively, diagnosed cases was initiated between 1991 and 1993. The 2201 patients with IBD (706 had Crohn's disease (CD), 1379 had ulcerative colitis (UC) and 116 had indeterminate colitis) originated from 20 different areas in 11 different European countries and Israel. For the 10-year follow-up of this cohort, electronic data-collecting instruments were made available through an Internet-based website. Data concerning vital status, disease activity, medication use, surgical events, cancer, pregnancy, fertility, quality of life and health-care costs were gathered. A blood sample was obtained from patients and controls to perform genotypic characterization. Thirteen centres from eight European countries and Israel participated. In 958 (316 CD and 642 UC) out of a total of 1505 IBD patients (64%) from these 13 centres, a complete dataset was obtained at follow-up. Even though an increased mortality risk was observed in CD patients 10 years after diagnosis, a benign disease course was observed in this patient group in terms of disease recurrence. A correlation between ASCA and CARD15 variants in CD patients and complicated disease course was observed. A north-south gradient was observed regarding colectomy rates in UC patients. Direct costs were found to be highest in the first year after diagnosis and greater in CD patients than in UC patients, with marked differences between participating countries. This 10-year clinical follow-up study of a population-based European cohort of IBD patients provides updated information on disease outcome of these patient groups.

Genetic diagnosis of X-linked dominant hypophosphatemic rickets in a cohort study: Tubular reabsorption of phosphate and 1,25(OH)2D serum levels are associated with PHEX mutation type

PubMed Central

2011-01-01

Background Genetic Hypophosphatemic Rickets (HR) is a group of diseases characterized by renal phosphate wasting with inappropriately low or normal 1,25-dihydroxyvitamin D3 (1,25(OH)2D) serum levels. The most common form of HR is X-linked dominant HR (XLHR) which is caused by inactivating mutations in the PHEX gene. The purpose of this study was to perform genetic diagnosis in a cohort of patients with clinical diagnosis of HR, to perform genotype-phenotype correlations of those patients and to compare our data with other HR cohort studies. Methods Forty three affected individuals from 36 non related families were analyzed. For the genetic analysis, the PHEX gene was sequenced in all of the patients and in 13 cases the study was complemented by mRNA sequencing and Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the clinical and biochemical phenotype of the patients was compared with the type of mutation, which was grouped into clearly deleterious or likely causative, using the Mann-Whitney and Fisher's exact test. Results Mutations in the PHEX gene were identified in all the patients thus confirming an XLHR. Thirty four different mutations were found distributed throughout the gene with higher density at the 3' end. The majority of the mutations were novel (69.4%), most of them resulted in a truncated PHEX protein (83.3%) and were family specific (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)2D serum levels were significantly lower in patients carrying clearly deleterious mutations than in patients carrying likely causative ones (61.39 ± 19.76 vs. 80.14 ± 8.80%, p = 0.028 and 40.93 ± 30.73 vs. 78.46 ± 36.27 pg/ml, p = 0.013). Conclusions PHEX gene mutations were found in all the HR cases analyzed, which was in contrast with other cohort studies. Patients with clearly deleterious PHEX mutations had lower TRP and 1,25(OH)2D levels suggesting that the PHEX type of mutation might predict the XLHR phenotype severity. PMID:21902834

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

Jensen, Anna M.; Warren, Jeffrey; Hanson, Paul J.

Using seasonal- and cohort-specific photosynthetic temperature response functions, we quantified the physiological significance of maintaining multiple foliar cohorts in mature (~40-45 year old) Picea mariana trees in an ombrotrophic Sphagnum-bog, northern Minnesota, USA. We measured photosynthetic capacity, foliar respiration (Rd), biochemistry and morphology to estimate annual carbon (C) uptake by cohort, season and canopy position. Temperature response of key photosynthetic parameters at 25 C (i.e., light-saturated rate of CO 2 assimilation (Asat), light-saturated rate of Rubisco carboxylation (Vcmax), light-saturated electron transport rate (Jmax)) were clearly dependent on season and were generally less responsive in younger needles. Temperature optimums range betweenmore » 18.7-23.7, 31.3-38.3 and 28.7-36.7 C for Asat, Vcmax and Jmax respectively. Current-year (Y0) foliage had lower photosynthetic capacities compared to one-year-old (Y1) and two-year-old (Y2) foliage. As Y0 needles matured, values of Asat, Vcmax, Jmax, foliar LMA and nitrogen increased. Values of Vcmax, Jmax and Rd were related to foliar nitrogen but only in the youngest (Y0) cohort. Foliar ontogeny affected photosynthetic capacity more than growth temperature. Morphological and physiological cohort differences were reflected by their annual contribution to modeled C uptake, with a ~36% lower estimated annual C uptake by Y0 needles (LAI 0.52 m 2m -2) compared to Y1&2 cohorts (LAI 0.67 m 2m -2). Collectively, these results illustrate the physiological and ecological significance of characterizing multiple foliar cohorts during bud break and throughout the growth season, and for cumulative C uptake model estimates.« less

The Research Implications of Prostate Specific Antigen Registry Errors: Data from the Veterans Health Administration.

PubMed

Guo, David P; Thomas, I-Chun; Mittakanti, Harsha R; Shelton, Jeremy B; Makarov, Danil V; Skolarus, Ted A; Cooperberg, Mathew R; Sonn, Geoffrey A; Chung, Benjamin I; Brooks, James D; Leppert, John T

2018-04-06

We sought to characterize the effects of prostate specific antigen registry errors on clinical research by comparing cohorts based on cancer registry prostate specific antigen values with those based directly on results in the electronic health record. We defined sample cohorts of men with prostate cancer using data from the VHA (Veterans Health Administration), including those with a prostate specific antigen value less than 4.0, 4.0 to 10.0, 10.0 to 20.0 and 20.0 to 98.0 ng/ml, respectively. We compared the composition of each cohort and overall patient survival when using PSA values from the VACCR (Veteran Affairs Central Cancer Registry) vs the gold standard electronic health record laboratory file results. There was limited agreement among cohorts when defined by cancer registry PSA values vs the laboratory file of the electronic health record. The least agreement of 58% was seen in patients with PSA less than 4.0 ng/ml and greatest agreement of 89% was noted among patients with PSA between 4.0 and 10.0 ng/ml. In each cohort patients assigned to a cohort based only on the cancer registry PSA value had significantly different overall survival when compared with patients assigned based on registry and laboratory file PSA values. Cohorts based exclusively on cancer registry PSA values may have high rates of misclassification that can introduce concerning differences in key characteristics and result in measurable differences in clinical outcomes. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Cardiovascular risk prediction tools for populations in Asia.

PubMed

Barzi, F; Patel, A; Gu, D; Sritara, P; Lam, T H; Rodgers, A; Woodward, M

2007-02-01

Cardiovascular risk equations are traditionally derived from the Framingham Study. The accuracy of this approach in Asian populations, where resources for risk factor measurement may be limited, is unclear. To compare "low-information" equations (derived using only age, systolic blood pressure, total cholesterol and smoking status) derived from the Framingham Study with those derived from the Asian cohorts, on the accuracy of cardiovascular risk prediction. Separate equations to predict the 8-year risk of a cardiovascular event were derived from Asian and Framingham cohorts. The performance of these equations, and a subsequently "recalibrated" Framingham equation, were evaluated among participants from independent Chinese cohorts. Six cohort studies from Japan, Korea and Singapore (Asian cohorts); six cohort studies from China; the Framingham Study from the US. 172,077 participants from the Asian cohorts; 25,682 participants from Chinese cohorts and 6053 participants from the Framingham Study. In the Chinese cohorts, 542 cardiovascular events occurred during 8 years of follow-up. Both the Asian cohorts and the Framingham equations discriminated cardiovascular risk well in the Chinese cohorts; the area under the receiver-operator characteristic curve was at least 0.75 for men and women. However, the Framingham risk equation systematically overestimated risk in the Chinese cohorts by an average of 276% among men and 102% among women. The corresponding average overestimation using the Asian cohorts equation was 11% and 10%, respectively. Recalibrating the Framingham risk equation using cardiovascular disease incidence from the non-Chinese Asian cohorts led to an overestimation of risk by an average of 4% in women and underestimation of risk by an average of 2% in men. A low-information Framingham cardiovascular risk prediction tool, which, when recalibrated with contemporary data, is likely to estimate future cardiovascular risk with similar accuracy in Asian populations as tools developed from data on local cohorts.

Characterization and structure of hypomania in a British nonclinical adolescent sample.

PubMed

Hosang, Georgina M; Cardno, Alastair G; Freeman, Daniel; Ronald, Angelica

2017-01-01

This study aimed to test the validity of using the Hypomania Checklist-16 [HCL-16] to measure hypomania in a British adolescent community sample. Limited research is available concerning the characterization of hypomania among community adolescent samples, particularly in the UK, despite its potential importance for early intervention policy development. To explore the structure and characterization of hypomania in a British adolescent nonclinical cohort, over 1400 17 year olds (Mean=17.05 years; SD=0.88) completed the HCL-16 along with measures of different psychological and psychopathological dimensions. Principal components analysis revealed a 2-component solution for the HCL-16, described as active-elated and irritable/risk-taking. Hypomanic symptoms were significantly correlated with many psychopathological dimensions. There were distinct correlation patterns for the two HCL-16 subscales, with the irritability/risk-taking subscale showing significantly stronger associations with psychotic-like experiences, internalizing and externalizing problems, and reduced life satisfaction relative to the active-elated dimension. Adolescents at 'high-risk' for bipolar disorder reported more psychopathology relative to the comparison group. Absence of the clinical diagnosis of bipolar disorder in the sample means that the classification of the 'high-risk' group cannot be confirmed. The structure of the HCL-16 in this UK adolescent sample mirrored that observed in adult and clinical cohorts. The observed links between the HCL-16 and psychopathological dimensions that have been previously associated with both hypomania and bipolar disorder lend support to the HCL-16's validity as a hypomania instrument for adolescents. Better understanding of hypomania prior to adulthood has considerable potential for informing early intervention approaches. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

The Genome of the Netherlands: design, and project goals

PubMed Central

Boomsma, Dorret I; Wijmenga, Cisca; Slagboom, Eline P; Swertz, Morris A; Karssen, Lennart C; Abdellaoui, Abdel; Ye, Kai; Guryev, Victor; Vermaat, Martijn; van Dijk, Freerk; Francioli, Laurent C; Hottenga, Jouke Jan; Laros, Jeroen F J; Li, Qibin; Li, Yingrui; Cao, Hongzhi; Chen, Ruoyan; Du, Yuanping; Li, Ning; Cao, Sujie; van Setten, Jessica; Menelaou, Androniki; Pulit, Sara L; Hehir-Kwa, Jayne Y; Beekman, Marian; Elbers, Clara C; Byelas, Heorhiy; de Craen, Anton J M; Deelen, Patrick; Dijkstra, Martijn; den Dunnen, Johan T; de Knijff, Peter; Houwing-Duistermaat, Jeanine; Koval, Vyacheslav; Estrada, Karol; Hofman, Albert; Kanterakis, Alexandros; Enckevort, David van; Mai, Hailiang; Kattenberg, Mathijs; van Leeuwen, Elisabeth M; Neerincx, Pieter B T; Oostra, Ben; Rivadeneira, Fernanodo; Suchiman, Eka H D; Uitterlinden, Andre G; Willemsen, Gonneke; Wolffenbuttel, Bruce H; Wang, Jun; de Bakker, Paul I W; van Ommen, Gert-Jan; van Duijn, Cornelia M

2014-01-01

Within the Netherlands a national network of biobanks has been established (Biobanking and Biomolecular Research Infrastructure-Netherlands (BBMRI-NL)) as a national node of the European BBMRI. One of the aims of BBMRI-NL is to enrich biobanks with different types of molecular and phenotype data. Here, we describe the Genome of the Netherlands (GoNL), one of the projects within BBMRI-NL. GoNL is a whole-genome-sequencing project in a representative sample consisting of 250 trio-families from all provinces in the Netherlands, which aims to characterize DNA sequence variation in the Dutch population. The parent–offspring trios include adult individuals ranging in age from 19 to 87 years (mean=53 years; SD=16 years) from birth cohorts 1910–1994. Sequencing was done on blood-derived DNA from uncultured cells and accomplished coverage was 14–15x. The family-based design represents a unique resource to assess the frequency of regional variants, accurately reconstruct haplotypes by family-based phasing, characterize short indels and complex structural variants, and establish the rate of de novo mutational events. GoNL will also serve as a reference panel for imputation in the available genome-wide association studies in Dutch and other cohorts to refine association signals and uncover population-specific variants. GoNL will create a catalog of human genetic variation in this sample that is uniquely characterized with respect to micro-geographic location and a wide range of phenotypes. The resource will be made available to the research and medical community to guide the interpretation of sequencing projects. The present paper summarizes the global characteristics of the project. PMID:23714750

Examination of Global Methylation and Targeted Imprinted Genes in Prader-Willi Syndrome.

PubMed

Manzardo, A M; Butler, M G

2016-01-01

Methylation changes observed in Prader-Willi syndrome (PWS) may impact global methylation as well as regional methylation status of imprinted genes on chromosome 15 (in cis) or other imprinted obesity-related genes on other chromosomes (in trans) leading to differential effects on gene expression impacting obesity phenotype unique to (PWS). Characterize the global methylation profiles and methylation status for select imprinted genes associated with obesity phenotype in a well-characterized imprinted, obesity-related syndrome (PWS) relative to a cohort of obese and non-obese individuals. Global methylation was assayed using two methodologies: 1) enriched LINE-1 repeat sequences by EpigenDx and 2) ELISA-based immunoassay method sensitive to genomic 5-methylcytosine by Epigentek. Target gene methylation patterns at selected candidate obesity gene loci were determined using methylation-specific PCR. Study participants were recruited as part of an ongoing research program on obesity-related genomics and Prader-Willi syndrome. Individuals with non-syndromic obesity (N=26), leanness (N=26) and PWS (N=39). A detailed characterization of the imprinting status of select target genes within the critical PWS 15q11-q13 genomic region showed enhanced cis but not trans methylation of imprinted genes. No significant differences in global methylation were found between non-syndromic obese, PWS or non-obese controls. None. Percentage methylation and the methylation index. The methylation abnormality in PWS due to errors of genomic imprinting effects both upstream and downstream effectors in the 15q11-q13 region showing enhanced cis but not trans methylation of imprinted genes. Obesity in our subject cohorts did not appear to impact global methylation levels using the described methodology.

Examination of Global Methylation and Targeted Imprinted Genes in Prader-Willi Syndrome

PubMed Central

Manzardo, AM; Butler, MG

2016-01-01

Context Methylation changes observed in Prader-Willi syndrome (PWS) may impact global methylation as well as regional methylation status of imprinted genes on chromosome 15 (in cis) or other imprinted obesity-related genes on other chromosomes (in trans) leading to differential effects on gene expression impacting obesity phenotype unique to (PWS). Objective Characterize the global methylation profiles and methylation status for select imprinted genes associated with obesity phenotype in a well-characterized imprinted, obesity-related syndrome (PWS) relative to a cohort of obese and non-obese individuals. Design Global methylation was assayed using two methodologies: 1) enriched LINE-1 repeat sequences by EpigenDx and 2) ELISA-based immunoassay method sensitive to genomic 5-methylcytosine by Epigentek. Target gene methylation patterns at selected candidate obesity gene loci were determined using methylation-specific PCR. Setting Study participants were recruited as part of an ongoing research program on obesity-related genomics and Prader-Willi syndrome. Participants Individuals with non-syndromic obesity (N=26), leanness (N=26) and PWS (N=39). Results A detailed characterization of the imprinting status of select target genes within the critical PWS 15q11-q13 genomic region showed enhanced cis but not trans methylation of imprinted genes. No significant differences in global methylation were found between non-syndromic obese, PWS or non-obese controls. Intervention None. Main outcome measures Percentage methylation and the methylation index. Conclusion The methylation abnormality in PWS due to errors of genomic imprinting effects both upstream and downstream effectors in the 15q11-q13 region showing enhanced cis but not trans methylation of imprinted genes. Obesity in our subject cohorts did not appear to impact global methylation levels using the described methodology. PMID:28111641

Exhaustively Characterizing a Patient Cohort by Prevalence of EMR Facts: a Generalized, Vendor-Agnostic Method for Quality Control and Research.

PubMed

Alex F, Bokov; Olin, Gail P; Bos, Angela; Tirado-Ramos, Alfredo; Kittrell, Pamela; Jackson, Carlayne

2017-01-01

We present a method for rapidly ranking all distinct facts in an electronic medical record (EMR) system by howover-represented or under-represented they are in a patient cohort of interest relative to some larger referencepopulation of patients in the same EMR. We have implemented this method as a plugin for i2b2, the open sourcedata warehouse platform widely used in research health informatics. Our method is highly flexible in terms of whatmedical terminologies it supports and is vendor-independent thanks to leveraging the i2b2 star schema rather thanany one specific EMR. It can be applied to a wide range of informatics problems including finding healthdisparities, searching for variables to include in a risk calculator or computable phenotype, detection ofcomorbidities, discovery of adverse drug reactions. The case study we present here uses this software to findunlabeled flowsheets for patients suffering from amyotrophic lateral sclerosis.

Household Exposure to Livestock and Health in the CHILILAB HDSS Cohort, Vietnam.

PubMed

Dang-Xuan, Sinh; MacDonald, Lauren E; Schurer, Janna M; Nguyen-Viet, Hung; Pham-Duc, Phuc

2017-07-01

In Vietnam, pigs and poultry are predominantly produced by small-scale farmers, creating challenges for zoonotic disease management. The objective of this study was to characterize practices related to livestock and manure management and to measure association with 3 self-reported health symptoms (coughing, fever, and diarrhea/nausea/vomiting) in a region currently undergoing health transitions. We analyzed cross-sectional survey data collected from a subset (N = 5520) of the Chi Linh Health and Demographic Surveillance System cohort in Chi Linh district, Vietnam. Bivariate analyses indicated that female gender was a significant risk factor for all 3 health symptoms, whereas age (≥60 years), suburban living, low education level, and household wealth were risk factors for 2 symptoms. Overall, we found no indication that biogas production or exposure to livestock and manure adversely affected human health. Efforts to control zoonotic disease transmission should prioritize utilization of veterinarians, enhanced farm biosecurity, and improvements to commune drinking water/wastewater infrastructure.

The child health exposure analysis resource as a vehicle to measure environment in the environmental influences on child health outcomes program.

PubMed

Wright, Robert O; Teitelbaum, Susan; Thompson, Claudia; Balshaw, David

2018-04-01

Demonstrate the role of environment as a predictor of child health. The children's health exposure analysis resource (CHEAR) assists the Environmental influences on child health outcomes (ECHO) program in understanding the time sensitive and dynamic nature of perinatal and childhood environment on developmental trajectories by providing a central infrastructure for the analysis of biological samples from the ECHO cohort awards. CHEAR will assist ECHO cohorts in defining the critical or sensitive period for effects associated with environmental exposures. Effective incorporation of these principles into multiple existing cohorts requires extensive multidisciplinary expertise, creativity, and flexibility. The pursuit of life course - informed research within the CHEAR/ECHO structure represents a shift in focus from single exposure inquiries to one that addresses multiple environmental risk factors linked through shared vulnerabilities. CHEAR provides ECHO both targeted analyses of inorganic and organic toxicants, nutrients, and social-stress markers and untargeted analyses to assess the exposome and discovery of exposure-outcome relationships. Utilization of CHEAR as a single site for characterization of environmental exposures within the ECHO cohorts will not only support the investigation of the influence of environment on children's health but also support the harmonization of data across the disparate cohorts that comprise ECHO.

Amino-Terminal Pro-B-Type Natriuretic Peptide and B-Type Natriuretic Peptide

PubMed Central

McKie, Paul M.; Rodeheffer, Richard J.; Cataliotti, Alessandro; Martin, Fernando L.; Urban, Lynn H.; Mahoney, Douglas W.; Jacobsen, Steven J.; Redfield, Margaret M.; Burnett, John C.

2007-01-01

Recent studies report that, in the absence of heart failure and renal failure, plasma B-type natriuretic peptide (BNP) has prognostic value for mortality. We sought to confirm and extend these previous studies to assess BNP, measured by 3 distinct assays, as a biomarker for mortality in a strategy to enhance efforts at primary prevention and to better understand the clinical phenotype of such subjects at risk. We used a community-based cohort of 2042 subjects from Olmsted County, Minn, and individuals with heart or renal failure were excluded. BNP was assessed using 3 assays including Biosite and Shionogi for mature, biologically active BNP and the Roche assay for apparently nonbiologically active amino-terminal pro-BNP (NT-proBNP). Thorough echocardiographic and clinical data were recorded for all of the participants. Median follow-up for mortality was 5.6 years. BNP by all 3 of the assays was predictive of mortality. NT-proBNP and Biosite assays remained significant even after adjustment for traditional clinical risk factors and echocardiographic abnormalities including left ventricular hypertrophy and diastolic dysfunction. Echocardiography documented widespread structural changes in those with increasing BNP levels yet below levels observed in heart failure. We report in a large, well-characterized community-based cohort, free of heart failure, the first study to compare 3 distinct BNP assays as biomarkers for mortality in the same cohort. Our findings confirm the potential use of NT-proBNP and BNP biomarkers for future events and underscore that these peptides may also serve as biomarkers for underlying cardiac remodeling secondary to diverse cardiovascular disease entities. PMID:16585413

LEUKEMIA, LYMPHOMA AND MULTIPLE MYELOMA MORTALITY (1950–1999) AND INCIDENCE (1969–1999) IN THE ELDORADO URANIUM WORKERS COHORT

PubMed Central

Zablotska, Lydia B.; Lane, Rachel S.D.; Frost, Stanley E.; Thompson, Patsy A.

2014-01-01

Uranium workers are chronically exposed to low levels of radon decay products (RDP) and gamma (γ) radiation. Risks of leukemia from acute and high doses of γ-radiation are well-characterized, but risks from lower doses and dose-rates and from RDP exposures are controversial. Few studies have evaluated risks of other hematologic cancers in uranium workers. The purpose of this study was to analyze radiation-related risks of hematologic cancers in the cohort of Eldorado uranium miners and processors first employed in 1932–1980 in relation to cumulative RDP exposures and γ-ray doses. The average cumulative RDP exposure was 100.2 working level months and the average cumulative whole-body γ-radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of hematologic cancers in the cohort. Overall, male workers had lower mortality and cancer incidence rates for all outcomes compared with the general Canadian male population, a likely healthy worker effect. No statistically significant association between RDP exposure or γ-ray doses, or a combination of both, and mortality or incidence of any hematologic cancer was found. We observed consistent but non-statistically significant increases in risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin lymphoma (NHL) mortality with increasing γ-ray doses. These findings are consistent with recent studies of increased risks of CLL and NHL incidence after γ-radiation exposure. Further research is necessary to understand risks of other hematologic cancers from low-dose exposures to γ-radiation. PMID:24583244

Molecular subgroups of adult medulloblastoma: a long-term single-institution study.

PubMed

Zhao, Fu; Ohgaki, Hiroko; Xu, Lei; Giangaspero, Felice; Li, Chunde; Li, Peng; Yang, Zhijun; Wang, Bo; Wang, Xingchao; Wang, Zhenmin; Ai, Lin; Zhang, Jing; Luo, Lin; Liu, Pinan

2016-07-01

Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort. We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics. Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes. We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Adult Congenital Heart Disease Patients Experience Similar Symptoms of Disease Activity.

PubMed

Cedars, Ari M; Stefanescu Schmidt, Ada; Broberg, Craig; Zaidi, Ali; Opotowsky, Alexander; Grewal, Jasmine; Kay, Joseph; Bhatt, Ami B; Novak, Eric; Spertus, John

2016-03-01

There is a lack of objective data on the symptoms characterizing disease activity among adults with congenital heart disease (ACHD). The purpose of this study was to elicit the most important symptoms from patients across the spectrum of ACHD and to examine whether reported symptoms were similar across the spectrum of ACHD as a foundation for creating a patient-reported outcome measure(s). We constructed a 39-item survey using input from physicians specializing in ACHD to assess the symptoms patients associate with disease activity. Patients (n=124) prospectively completed this survey, and the results were analyzed based on underlying anatomy and disease complexity. A confirmatory cohort of patients (n=40) was then recruited prospectively to confirm the validity of the initial data. When grouped based on underlying anatomy, significant differences in disease-related symptom rankings were found for only 6 of 39 symptoms. Six symptoms were identified which were of particular significance to patients, regardless of underlying anatomy. Patients with anatomy of great complexity experienced greater overall symptom severity than those with anatomy of low or moderate complexity, attributable exclusively to higher ranking of 5 symptoms. The second patient cohort had symptom experiences similar to those of the initial cohort, differing in only 5 of 39 symptoms. This study identified 6 symptoms relevant to patients across the spectrum of ACHD and remarkable homogeneity of patient experience, suggesting that a single disease-specific patient-reported outcome can be created for quality and outcome assessments. © 2016 American Heart Association, Inc.

A Genetic Basis for Mechanosensory Traits in Humans

PubMed Central

Frenzel, Henning; Bohlender, Jörg; Pinsker, Katrin; Wohlleben, Bärbel; Tank, Jens; Lechner, Stefan G.; Schiska, Daniela; Jaijo, Teresa; Rüschendorf, Franz; Saar, Kathrin; Jordan, Jens; Millán, José M.; Gross, Manfred; Lewin, Gary R.

2012-01-01

In all vertebrates hearing and touch represent two distinct sensory systems that both rely on the transformation of mechanical force into electrical signals. There is an extensive literature describing single gene mutations in humans that cause hearing impairment, but there are essentially none for touch. Here we first asked if touch sensitivity is a heritable trait and second whether there are common genes that influence different mechanosensory senses like hearing and touch in humans. Using a classical twin study design we demonstrate that touch sensitivity and touch acuity are highly heritable traits. Quantitative phenotypic measures of different mechanosensory systems revealed significant correlations between touch and hearing acuity in a healthy human population. Thus mutations in genes causing deafness genes could conceivably negatively influence touch sensitivity. In agreement with this hypothesis we found that a proportion of a cohort of congenitally deaf young adults display significantly impaired measures of touch sensitivity compared to controls. In contrast, blind individuals showed enhanced, not diminished touch acuity. Finally, by examining a cohort of patients with Usher syndrome, a genetically well-characterized deaf-blindness syndrome, we could show that recessive pathogenic mutations in the USH2A gene influence touch acuity. Control Usher syndrome cohorts lacking demonstrable pathogenic USH2A mutations showed no impairment in touch acuity. Our study thus provides comprehensive evidence that there are common genetic elements that contribute to touch and hearing and has identified one of these genes as USH2A. PMID:22563300

Epidemiologic Tools to Study the Influence of Environmental Factors on Fecundity and Pregnancy-related Outcomes

PubMed Central

Slama, Rémy; Ballester, Ferran; Casas, Maribel; Cordier, Sylvaine; Eggesbø, Merete; Iniguez, Carmen; Nieuwenhuijsen, Mark; Philippat, Claire; Rey, Sylvie; Vandentorren, Stéphanie; Vrijheid, Martine

2014-01-01

Adverse pregnancy outcomes entail a large health burden for the mother and offspring; a part of it might be avoided by better understanding the role of environmental factors in their etiology. Our aims were to review the assessment tools to characterize fecundity troubles and pregnancy-related outcomes in human populations and their sensitivity to environmental factors. For each outcome, we reviewed the possible study designs, main sources of bias, and their suggested cures. In terms of study design, for most pregnancy outcomes, cohorts with recruitment early during or even before pregnancy allow efficient characterization of pregnancy-related events, time-varying confounders, and in utero exposures that may impact birth outcomes and child health. Studies on congenital anomalies require specific designs, assessment of anomalies in medical pregnancy terminations, and, for congenital anomalies diagnosed postnatally, follow-up during several months after birth. Statistical analyses should take into account environmental exposures during the relevant time windows; survival models are an appropriate approach for fecundity, fetal loss, and gestational duration/preterm delivery. Analysis of gestational duration could distinguish pregnancies according to delivery induction (and possibly pregnancy-related conditions). In conclusion, careful design and analysis are required to better characterize environmental effects on human reproduction. PMID:24363355

Characterizing the course of back pain after osteoporotic vertebral fracture: a hierarchical cluster analysis of a prospective cohort study.

PubMed

Toyoda, Hiromitsu; Takahashi, Shinji; Hoshino, Masatoshi; Takayama, Kazushi; Iseki, Kazumichi; Sasaoka, Ryuichi; Tsujio, Tadao; Yasuda, Hiroyuki; Sasaki, Takeharu; Kanematsu, Fumiaki; Kono, Hiroshi; Nakamura, Hiroaki

2017-09-23

This study demonstrated four distinct patterns in the course of back pain after osteoporotic vertebral fracture (OVF). Greater angular instability in the first 6 months after the baseline was one factor affecting back pain after OVF. Understanding the natural course of symptomatic acute OVF is important in deciding the optimal treatment strategy. We used latent class analysis to classify the course of back pain after OVF and identify the risk factors associated with persistent pain. This multicenter cohort study included 218 consecutive patients with ≤ 2-week-old OVFs who were enrolled at 11 institutions. Dynamic x-rays and back pain assessment with a visual analog scale (VAS) were obtained at enrollment and at 1-, 3-, and 6-month follow-ups. The VAS scores were used to characterize patient groups, using hierarchical cluster analysis. VAS for 128 patients was used for hierarchical cluster analysis. Analysis yielded four clusters representing different patterns of back pain progression. Cluster 1 patients (50.8%) had stable, mild pain. Cluster 2 patients (21.1%) started with moderate pain and progressed quickly to very low pain. Patients in cluster 3 (10.9%) had moderate pain that initially improved but worsened after 3 months. Cluster 4 patients (17.2%) had persistent severe pain. Patients in cluster 4 showed significant high baseline pain intensity, higher degree of angular instability, and higher number of previous OVFs, and tended to lack regular exercise. In contrast, patients in cluster 2 had significantly lower baseline VAS and less angular instability. We identified four distinct groups of OVF patients with different patterns of back pain progression. Understanding the course of back pain after OVF may help in its management and contribute to future treatment trials.

Dissecting the role of non-coding RNAs in the accumulation of amyloid and tau neuropathologies in Alzheimer's disease.

PubMed

Patrick, Ellis; Rajagopal, Sathyapriya; Wong, Hon-Kit Andus; McCabe, Cristin; Xu, Jishu; Tang, Anna; Imboywa, Selina H; Schneider, Julie A; Pochet, Nathalie; Krichevsky, Anna M; Chibnik, Lori B; Bennett, David A; De Jager, Philip L

2017-07-01

Given multiple studies of brain microRNA (miRNA) in relation to Alzheimer's disease (AD) with few consistent results and the heterogeneity of this disease, the objective of this study was to explore their mechanism by evaluating their relation to different elements of Alzheimer's disease pathology, confounding factors and mRNA expression data from the same subjects in the same brain region. We report analyses of expression profiling of miRNA (n = 700 subjects) and lincRNA (n = 540 subjects) from the dorsolateral prefrontal cortex of individuals participating in two longitudinal cohort studies of aging. We confirm the association of two well-established miRNA (miR-132, miR-129) with pathologic AD in our dataset and then further characterize this association in terms of its component neuritic β-amyloid plaques and neurofibrillary tangle pathologies. Additionally, we identify one new miRNA (miR-99) and four lincRNA that are associated with these traits. Many other previously reported associations of microRNA with AD are associated with the confounders quantified in our longitudinal cohort. Finally, by performing analyses integrating both miRNA and RNA sequence data from the same individuals (525 samples), we characterize the impact of AD associated miRNA on human brain expression: we show that the effects of miR-132 and miR-129-5b converge on certain genes such as EP300 and find a role for miR200 and its target genes in AD using an integrated miRNA/mRNA analysis. Overall, miRNAs play a modest role in human AD, but we observe robust evidence that a small number of miRNAs are responsible for specific alterations in the cortical transcriptome that are associated with AD.

Evaluating Quality Metrics and Cost After Discharge: A Population-based Cohort Study of Value in Health Care Following Elective Major Vascular Surgery.

PubMed

de Mestral, Charles; Salata, Konrad; Hussain, Mohamad A; Kayssi, Ahmed; Al-Omran, Mohammed; Roche-Nagle, Graham

2018-04-18

Early readmission to hospital after surgery is an omnipresent quality metric across surgical fields. We sought to understand the relative importance of hospital readmission among all health services received after hospital discharge. The aim of this study was to characterize 30-day postdischarge cost and risk of an emergency department (ED) visit, readmission, or death after hospitalization for elective major vascular surgery. This is a population-based retrospective cohort study of patients who underwent elective major vascular surgery - carotid endarterectomy, EVAR, open AAA repair, bypass for lower extremity peripheral arterial disease - in Ontario, Canada, between 2004 and 2015. The outcomes of interest included quality metrics - ED visit, readmission, death - and cost to the Ministry of Health, within 30 days of discharge. Costs after discharge included those attributable to hospital readmission, ED visits, rehab, physician billing, outpatient nursing and allied health care, medications, interventions, and tests. Multivariable regression models characterized the association of pre-discharge characteristics with the above-mentioned postdischarge quality metrics and cost. A total of 30,752 patients were identified. Within 30 days of discharge, 2588 (8.4%) patients were readmitted to hospital and 13 patients died (0.04%). Another 4145 (13.5%) patients visited an ED without requiring admission. Across all patients, over half of 30-day postdischarge costs were attributable to outpatient care. Patients at an increased risk of an ED visit, readmission, or death within 30 days of discharge differed from those patients with relatively higher 30-day costs. Events occurring outside the hospital setting should be integral to the evaluation of quality of care and cost after hospitalization for major vascular surgery.

Trajectory of frequency stability in typical development.

PubMed

Frohlich, Joel; Irimia, Andrei; Jeste, Shafali S

2015-03-01

This work explores a feature of brain dynamics, metastability, by which transients are observed in functional brain data. Metastability is a balance between static (stable) and dynamic (unstable) tendencies in electrophysiological brain activity. Furthermore, metastability is a theoretical mechanism underlying the rapid synchronization of cell assemblies that serve as neural substrates for cognitive states, and it has been associated with cognitive flexibility. While much previous research has sought to characterize metastability in the adult human brain, few studies have examined metastability in early development, in part because of the challenges of acquiring adequate, noise free continuous data in young children. To accomplish this endeavor, we studied a new method for characterizing the stability of EEG frequency in early childhood, as inspired by prior approaches for describing cortical phase resets in the scalp EEG of healthy adults. Specifically, we quantified the variance of the rate of change of the signal phase (i.e., frequency) as a proxy for phase resets (signal instability), given that phase resets occur almost simultaneously across large portions of the scalp. We tested our method in a cohort of 39 preschool age children (age =53 ± 13.6 months). We found that our outcome variable of interest, frequency variance, was a promising marker of signal stability, as it increased with the number of phase resets in surrogate (artificial) signals. In our cohort of children, frequency variance decreased cross-sectionally with age (r = -0.47, p = 0.0028). EEG signal stability, as quantified by frequency variance, increases with age in preschool age children. Future studies will relate this biomarker with the development of executive function and cognitive flexibility in children, with the overarching goal of understanding metastability in atypical development.

The human early-life exposome (HELIX): project rationale and design.

PubMed

Vrijheid, Martine; Slama, Rémy; Robinson, Oliver; Chatzi, Leda; Coen, Muireann; van den Hazel, Peter; Thomsen, Cathrine; Wright, John; Athersuch, Toby J; Avellana, Narcis; Basagaña, Xavier; Brochot, Celine; Bucchini, Luca; Bustamante, Mariona; Carracedo, Angel; Casas, Maribel; Estivill, Xavier; Fairley, Lesley; van Gent, Diana; Gonzalez, Juan R; Granum, Berit; Gražulevičienė, Regina; Gutzkow, Kristine B; Julvez, Jordi; Keun, Hector C; Kogevinas, Manolis; McEachan, Rosemary R C; Meltzer, Helle Margrete; Sabidó, Eduard; Schwarze, Per E; Siroux, Valérie; Sunyer, Jordi; Want, Elizabeth J; Zeman, Florence; Nieuwenhuijsen, Mark J

2014-06-01

Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure-health effect relationships. The "exposome" concept encompasses the totality of exposures from conception onward, complementing the genome. The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the "early-life exposome." Here we describe the general design of the project. In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother-child pairs, and biomarkers will be measured in a subset of 1,200 mother-child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure-response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

Molecular and Clinical Characterization of Albinism in a Large Cohort of Italian Patients

PubMed Central

Gargiulo, Annagiusi; Testa, Francesco; Rossi, Settimio; Di Iorio, Valentina; Fecarotta, Simona; de Berardinis, Teresa; Iovine, Antonello; Magli, Adriano; Signorini, Sabrina; Fazzi, Elisa; Galantuomo, Maria Silvana; Fossarello, Maurizio; Montefusco, Sandro; Ciccodicola, Alfredo; Neri, Alberto; Macaluso, Claudio; Simonelli, Francesca; Surace, Enrico Maria

2011-01-01

Purpose. The purpose of this study was to identify the molecular basis of albinism in a large cohort of Italian patients showing typical ocular landmarks of the disease and to provide a full characterization of the clinical ophthalmic manifestations. Methods. DNA samples from 45 patients with ocular manifestations of albinism were analyzed by direct sequencing analysis of five genes responsible for albinism: TYR, P, TYRP1, SLC45A2 (MATP), and OA1. All patients studied showed a variable degree of skin and hair hypopigmentation. Eighteen patients with distinct mutations in each gene associated with OCA were evaluated by detailed ophthalmic analysis, optical coherence tomography (OCT), and fundus autofluorescence. Results. Disease-causing mutations were identified in more than 95% of analyzed patients with OCA (28/45 [62.2%] cases with two or more mutations; 15/45 [33.3%] cases with one mutation). Thirty-five different mutant alleles were identified of which 15 were novel. Mutations in TYR were the most frequent (73.3%), whereas mutations in P occurred more rarely (13.3%) than previously reported. Novel mutations were also identified in rare loci such as TYRP1 and MATP. Mutations in the OA1 gene were not detected. Clinical assessment revealed that patients with iris and macular pigmentation had significantly higher visual acuity than did severe hypopigmented phenotypes. Conclusions. TYR gene mutations represent a relevant cause of oculocutaneous albinism in Italy, whereas mutations in P present a lower frequency than that found in other populations. Clinical analysis revealed that the severity of the ocular manifestations depends on the degree of retinal pigmentation. PMID:20861488

Performance on a computerized neurocognitive battery in 22q11.2 deletion syndrome: A comparison between US and Israeli cohorts

PubMed Central

Yi, James J.; Weinberger, Ronnie; Moore, Tyler M.; Calkins, Monica E.; Guri, Yael; McDonald-McGinn, Donna M.; Zackai, Elaine H.; Emanuel, Beverly S.; Gur, Raquel E.; Gothelf, Doron; Gur, Ruben C.

2016-01-01

Increasingly, the effects of copy number variation (CNV) in the genome on brain function and behaviors are recognized as means to elucidate pathophysiology of psychiatric disorders. Such studies require large samples and we characterized the neurocognitive profile of two cohorts of individuals with 22q11.2 deletion syndrome (22q11DS), the most common CNV associated with schizophrenia, in an effort to harmonize phenotyping in multi-site global collaborations. The Penn Computerized Neurocognitive Battery (PCNB) was administered to individuals with 22q11DS in Philadelphia (PHL; n=155, aged 12–40) and Tel Aviv (TLV; n=59, aged 12–36). We examined effect sizes of performance differences between the cohorts and confirmed the factor structure of PCNB performance efficiency in the combined sample based on data from a large comparison community sample. The cohorts performed comparably with notable deficits in executive function, episodic memory and social cognition domains that were previously associated with abnormal neuroimaging findings in 22q11DS. In mixed model analysis, while there was a main effect for site for accuracy (number of correct response) and speed (time to correct response) independently, there were no main site effects for standardized efficiency (average of accuracy and speed). The fit of a structural model was excellent indicating that PCNB tests were related to the targeted cognitive domains. Thus, our results provide preliminary support for the use of the PCNB as an efficient tool for neurocognitive assessment in international 22q11DS collaborations. PMID:27200494

Development and validation of a surgical-pathologic staging and scoring system for cervical cancer.

PubMed

Li, Shuang; Li, Xiong; Zhang, Yuan; Zhou, Hang; Tang, Fangxu; Jia, Yao; Hu, Ting; Sun, Haiying; Yang, Ru; Chen, Yile; Cheng, Xiaodong; Lv, Weiguo; Wu, Li; Zhou, Jin; Wang, Shaoshuai; Huang, Kecheng; Wang, Lin; Yao, Yuan; Yang, Qifeng; Yang, Xingsheng; Zhang, Qinghua; Han, Xiaobing; Lin, Zhongqiu; Xing, Hui; Qu, Pengpeng; Cai, Hongbing; Song, Xiaojie; Tian, Xiaoyu; Shen, Jian; Xi, Ling; Li, Kezhen; Deng, Dongrui; Wang, Hui; Wang, Changyu; Wu, Mingfu; Zhu, Tao; Chen, Gang; Gao, Qinglei; Wang, Shixuan; Hu, Junbo; Kong, Beihua; Xie, Xing; Ma, Ding

2016-04-12

Most cervical cancer patients worldwide receive surgical treatments, and yet the current International Federation of Gynecology and Obstetrics (FIGO) staging system do not consider surgical-pathologic data. We propose a more comprehensive and prognostically valuable surgical-pathologic staging and scoring system (SPSs). Records from 4,220 eligible cervical cancer cases (Cohort 1) were screened for surgical-pathologic risk factors. We constructed a surgical-pathologic staging and SPSs, which was subsequently validated in a prospective study of 1,104 cervical cancer patients (Cohort 2). In Cohort 1, seven independent risk factors were associated with patient outcome: lymph node metastasis (LNM), parametrial involvement, histological type, grade, tumor size, stromal invasion, and lymph-vascular space invasion (LVSI). The FIGO staging system was revised and expanded into a surgical-pathologic staging system by including additional criteria of LNM, stromal invasion, and LVSI. LNM was subdivided into three categories based on number and location of metastases. Inclusion of all seven prognostic risk factors improves practical applicability. Patients were stratified into three SPSs risk categories: zero-, low-, and high-score with scores of 0, 1 to 3, and ≥4 (P=1.08E-45; P=6.15E-55). In Cohort 2, 5-year overall survival (OS) and disease-free survival (DFS) outcomes decreased with increased SPSs scores (P=9.04E-15; P=3.23E-16), validating the approach. Surgical-pathologic staging and SPSs show greater homogeneity and discriminatory utility than FIGO staging. Surgical-pathologic staging and SPSs improve characterization of tumor severity and disease invasion, which may more accurately predict outcome and guide postoperative therapy.

Stroke after Aortic Valve Surgery: Results from a Prospective Cohort

PubMed Central

Messé, Steven R.; Acker, Michael A.; Kasner, Scott E.; Fanning, Molly; Giovannetti, Tania; Ratcliffe, Sarah J.; Bilello, Michel; Szeto, Wilson Y.; Bavaria, Joseph E.; Hargrove, W. Clark; Mohler, Emile R.; Floyd, Thomas F.

2014-01-01

Background The incidence and impact of clinical stroke and silent radiographic cerebral infarction complicating open surgical aortic valve replacement (AVR) are poorly characterized. Methods and Results We performed a prospective cohort study of subjects ≥ 65 years of age undergoing AVR for calcific aortic stenosis. Subjects were evaluated by neurologists pre-operatively and post-operatively, and underwent post-operative magnetic resonance imaging (MRI). Over a 4 year period, 196 subjects were enrolled at 2 sites. Mean age = 75.8 ± 6.2 years, 36% female, 6% non-white. Clinical strokes were detected in 17%, Transient Ischemic Attack in 2%, and in-hospital mortality was 5%. The frequency of stroke in the Society for Thoracic Surgery (STS) database in this cohort was 7%. Most strokes were mild; the median National Institutes of Health Stroke Scale (NIHSS) was 3 (interquartile range 1 – 9). Clinical stroke was associated with increased length of stay, median 12 vs 10 days, p = 0.02. Moderate or severe stroke (NIHSS ≥10) occurred in 8 (4%) and was strongly associated with in-hospital mortality, 38% vs 4%, p = 0.005. Of the 109 stroke-free subjects with post-operative MRI, silent infarct was identified in 59 (54%). Silent infarct was not associated with in-hospital mortality or increased length of stay. Conclusions Clinical stroke after AVR was more common than previously reported, more than double for this same cohort in the STS database, and silent cerebral infarctions were detected in over half of patients undergoing AVR. Clinical stroke complicating AVR is associated with increased length of stay and mortality. PMID:24690611

Epigenome-wide DNA methylation analysis in siblings and monozygotic twins discordant for sporadic Parkinson's disease revealed different epigenetic patterns in peripheral blood mononuclear cells.

PubMed

Kaut, Oliver; Schmitt, Ina; Tost, Jörg; Busato, Florence; Liu, Yi; Hofmann, Per; Witt, Stephanie H; Rietschel, Marcella; Fröhlich, Holger; Wüllner, Ullrich

2017-01-01

Numerous studies have elucidated the genetics of Parkinson's disease; however, the aetiology of the majority of sporadic cases has not yet been resolved. We hypothesized that epigenetic variations could be associated with PD and evaluated the DNA methylation pattern in PD patients compared to brothers or twins without PD. The methylation of DNA from peripheral blood mononuclear cells of 62 discordant siblings including 24 monozygotic twins was characterized with Illumina DNA Methylation 450K bead arrays and subsequently validated in two independent cohorts: 221 PD vs. 227 healthy individuals (cohort 1) applying Illumina's VeraCode and 472 PD patients vs. 487 controls (cohort 2) using pyrosequencing. We choose a delta beta of >15 % and selected 62 differentially methylated CpGs in 51 genes from the discordant siblings. Among them, three displayed multiple CpGs per gene: microRNA 886 (MIR886, 10 CpGs), phosphodiesterase 4D (PDE4D, 2 CpGs) and tripartite motif-containing 34 (TRIM34, 2 CpGs). PDE4D was confirmed in both cohorts (p value 2.44e-05). In addition, for biomarker construction, we used the penalized logistic regression model, resulting in a signature of eight CpGs with an AUC of 0.77. Our findings suggest that a distinct level of PD susceptibility stems from individual, epigenetic modifications of specific genes. We identified a signature of CpGs in blood cells that could separate control from disease with a reasonable discriminatory power, holding promise for future epigenetically based biomarker development.

Performance on a computerized neurocognitive battery in 22q11.2 deletion syndrome: A comparison between US and Israeli cohorts.

PubMed

Yi, James J; Weinberger, Ronnie; Moore, Tyler M; Calkins, Monica E; Guri, Yael; McDonald-McGinn, Donna M; Zackai, Elaine H; Emanuel, Beverly S; Gur, Raquel E; Gothelf, Doron; Gur, Ruben C

2016-07-01

Increasingly, the effects of copy number variation (CNV) in the genome on brain function and behaviors are recognized as means to elucidate pathophysiology of psychiatric disorders. Such studies require large samples and we characterized the neurocognitive profile of two cohorts of individuals with 22q11.2 deletion syndrome (22q11DS), the most common CNV associated with schizophrenia, in an effort to harmonize phenotyping in multi-site global collaborations. The Penn Computerized Neurocognitive Battery (PCNB) was administered to individuals with 22q11DS in Philadelphia (PHL; n=155, aged 12-40) and Tel Aviv (TLV; n=59, aged 12-36). We examined effect sizes of performance differences between the cohorts and confirmed the factor structure of PCNB performance efficiency in the combined sample based on data from a large comparison community sample. The cohorts performed comparably with notable deficits in executive function, episodic memory and social cognition domains that were previously associated with abnormal neuroimaging findings in 22q11DS. In mixed model analysis, while there was a main effect for site for accuracy (number of correct response) and speed (time to correct response) independently, there were no main site effects for standardized efficiency (average of accuracy and speed). The fit of a structural model was excellent indicating that PCNB tests were related to the targeted cognitive domains. Thus, our results provide preliminary support for the use of the PCNB as an efficient tool for neurocognitive assessment in international 22q11DS collaborations. Copyright © 2016 Elsevier Inc. All rights reserved.

Student Typologies in Higher Education

ERIC Educational Resources Information Center

Hu, Shouping; Katherine, Lindsey; Kuh, George D.

2011-01-01

One way to understand the college student experience is the generational approach, which examines the characteristics and attitudes of cohorts across different periods in history. Terms such as "baby boomers," "generation X," and "millennials" convey powerful images that characterize different generations according to who they are and what they…

Hyperemesis gravidarum and pregnancy outcomes in the Norwegian Mother and Child Cohort - a cohort study.

PubMed

Vikanes, Åse V; Støer, Nathalie C; Magnus, Per; Grjibovski, Andrej M

2013-09-03

Hyperemesis gravidarum (HG) characterized by excessive nausea and vomiting in early pregnancy, is reported to be associated with increased risks for low birthweight (LBW), preterm birth (PTB), small-for-gestational-age (SGA) and perinatal death. Conflicting results in previous studies underline the necessity to study HG's potential effect on pregnancy outcomes using large cohorts with valid data on exposure and outcome measures, as well as potential confounders. This study aims to investigate associations between HG and adverse pregnancy outcomes using the Norwegian Mother and Child Cohort Study (MoBa). All singleton pregnancies in MoBa from 1998 to 2008 were included. Multivariable regression was used to estimate relative risks, approximated by odds ratios, for PTB, LBW, SGA and perinatal death. Linear regression was applied to assess differences in birthweight and gestational age for children born to women with and without HG. Potential confounders were adjusted for. Altogether, 814 out of 71,468 women (or 1.1%) had HG. In MoBa HG was not associated with PTB, LBW or SGA. Babies born to women with HG were born on average 1 day earlier than those born to women without HG; (-0.97 day (95% confidence intervals (CI): -1.80 - -0.15). There was no difference in birthweight when maternal weight gain was adjusted for; (23.42 grams (95% CI: -56.71 - 9.86). Babies born by women with HG had lower risk for having Apgar score < 7 after 1 minute (crude odds ratio was 0.64 (95% CI: 0.43 - 0.95)). No differences between the groups for Apgar score < 7 after 5 minutes were observed. Time-point for hospitalisation slightly increased differences in gestational age according to maternal HG status. HG was not associated with adverse pregnancy outcomes. Pregnancies complicated with HG had a slightly shorter gestational length. There was no difference in birth weight according to maternal HG-status. HG was associated with an almost 40% reduced risk for having Apgar score < 7 after 1 minute, but not after 5 minutes. The clinical importance of these statistically significant findings is, however, rather limited.

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

PubMed

Lee, Hye Ah; Park, Hyesook

2012-09-01

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

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

PubMed Central

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

2012-01-01

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

Sciatic Nerve Injury After Proximal Hamstring Avulsion and Repair

PubMed Central

Wilson, Thomas J.; Spinner, Robert J.; Mohan, Rohith; Gibbs, Christopher M.; Krych, Aaron J.

2017-01-01

Background: Muscle bellies of the hamstring muscles are intimately associated with the sciatic nerve, putting the sciatic nerve at risk of injury associated with proximal hamstring avulsion. There are few data informing the magnitude of this risk, identifying risk factors for neurologic injury, or determining neurologic outcomes in patients with distal sciatic symptoms after surgery. Purpose: To characterize the frequency and nature of sciatic nerve injury and distal sciatic nerve–related symptoms after proximal hamstring avulsion and to characterize the influence of surgery on these symptoms. Study Design: Cohort study; Level of evidence, 3. Methods: This was a retrospective review of patients with proximal partial or complete hamstring avulsion. The outcome of interest was neurologic symptoms referable to the sciatic nerve distribution below the knee. Neurologic symptoms in operative patients were compared pre- and postoperatively. Results: The cohort consisted of 162 patients: 67 (41.4%) operative and 95 (58.6%) nonoperative. Sciatic nerve–related symptoms were present in 22 operative and 23 nonoperative patients, for a total of 45 (27.8%) patients (8 [4.9%] motor deficits, 11 [6.8%] sensory deficits, and 36 [22.2%] with neuropathic pain). Among the operative cohort, 3 of 3 (100.0%) patients showed improvement in their motor deficit postoperatively, 3 of 4 (75.0%) patients’ sensory symptoms improved, and 17 of 19 (89.5%) patients had improvement in pain. A new or worsening deficit occurred in 5 (7.5%) patients postoperatively (2 [3.1%] motor deficits, 1 [1.5%] sensory deficit, and 3 [4.5%] with new pain). Predictors of operative intervention included lower age (odds ratio [OR], 0.952; 95% CI, 0.921-0.982; P = .001) and complete avulsion (OR, 10.292; 95% CI, 2.526-72.232; P < .001). Presence of neurologic deficit was not predictive. Conclusion: Sciatic nerve–related symptoms after proximal hamstring avulsion are underrecognized. Currently, neurologic symptoms are not considered when determining whether to pursue operative intervention. Given the high likelihood of improvement with surgical treatment, neurologic symptoms should be considered when making a decision regarding operative treatment. PMID:28758137

A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis.

PubMed

Phatak, Pradyumna; Brissot, Pierre; Wurster, Mark; Adams, Paul C; Bonkovsky, Herbert L; Gross, John; Malfertheiner, Peter; McLaren, Gordon D; Niederau, Claus; Piperno, Alberto; Powell, Lawrie W; Russo, Mark W; Stoelzel, Ulrich; Stremmel, Wolfgang; Griffel, Louis; Lynch, Nicola; Zhang, Yiyun; Pietrangelo, Antonello

2010-11-01

Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in iron overload. Although phlebotomy is widely practiced, it is poorly tolerated or contraindicated in patients with anemias, severe heart disease, or poor venous access, and compliance can vary. The once-daily, oral iron chelator, deferasirox (Exjade) may provide an alternative treatment option. Patients with HH carrying the HFE gene who were homozygous for the Cys282Tyr mutation, serum ferritin levels of 300-2000 ng/mL, transferrin saturation ≥ 45%, and no known history of cirrhosis were enrolled in this dose-escalation study to characterize the safety and efficacy of deferasirox, comprising a core and an extension phase (each 24 weeks). Forty-nine patients were enrolled and received starting deferasirox doses of 5 (n = 11), 10 (n = 15), or 15 (n = 23) mg/kg/day. Adverse events were generally dose-dependent, the most common being diarrhea, headache, and nausea (n = 18, n = 10, and n = 8 in the core and n = 1, n = 1, and n = 0 in the extension, respectively). More patients in the 15 mg/kg/day than in the 5 or 10 mg/kg/day cohorts experienced increases in alanine aminotransferase and serum creatinine levels during the 48-week treatment period; six patients had alanine aminotransferase > 3 × baseline and greater than the upper limit of normal range, and eight patients had serum creatinine > 33% above baseline and greater than upper limit of normal on two consecutive occasions. After receiving deferasirox for 48 weeks, median serum ferritin levels decreased by 63.5%, 74.8%, and 74.1% in the 5, 10, and 15 mg/kg/day cohorts, respectively. In all cohorts, median serum ferritin decreased to < 250 ng/mL. Deferasirox doses of 5, 10, and 15 mg/kg/day can reduce iron burden in patients with HH. Based on the safety and efficacy results, starting deferasirox at 10 mg/kg/day appears to be most appropriate for further study in this patient population.

A Phase 1/2, Dose-Escalation Trial of Deferasirox for the Treatment of Iron Overload in HFE-Related Hereditary Hemochromatosis

PubMed Central

Phatak, Pradyumna; Brissot, Pierre; Wurster, Mark; Adams, Paul C; Bonkovsky, Herbert L; Gross, John; Malfertheiner, Peter; McLaren, Gordon D; Niederau, Claus; Piperno, Alberto; Powell, Lawrie W; Russo, Mark W; Stoelzel, Ulrich; Stremmel, Wolfgang; Griffel, Louis; Lynch, Nicola; Zhang, Yiyun; Pietrangelo, Antonello

2010-01-01

Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in iron overload. Although phlebotomy is widely practiced, it is poorly tolerated or contraindicated in patients with anemias, severe heart disease, or poor venous access, and compliance can vary. The once-daily, oral iron chelator, deferasirox (Exjade) may provide an alternative treatment option. Patients with HH carrying the HFE gene who were homozygous for the Cys282Tyr mutation, serum ferritin levels of 300-2000 ng/mL, transferrin saturation ≥45%, and no known history of cirrhosis were enrolled in this dose-escalation study to characterize the safety and efficacy of deferasirox, comprising a core and an extension phase (each 24 weeks). Forty-nine patients were enrolled and received starting deferasirox doses of 5 (n = 11), 10 (n = 15), or 15 (n = 23) mg/kg/day. Adverse events were generally dose-dependent, the most common being diarrhea, headache, and nausea (n = 18, n = 10, and n = 8 in the core and n = 1, n = 1, and n = 0 in the extension, respectively). More patients in the 15 mg/kg/day than in the 5 or 10 mg/kg/day cohorts experienced increases in alanine aminotransferase and serum creatinine levels during the 48-week treatment period; six patients had alanine aminotransferase >3× baseline and greater than the upper limit of normal range, and eight patients had serum creatinine >33% above baseline and greater than upper limit of normal on two consecutive occasions. After receiving deferasirox for 48 weeks, median serum ferritin levels decreased by 63.5%, 74.8%, and 74.1% in the 5, 10, and 15 mg/kg/day cohorts, respectively. In all cohorts, median serum ferritin decreased to <250 ng/mL. Conclusion: Deferasirox doses of 5, 10, and 15 mg/kg/day can reduce iron burden in patients with HH. Based on the safety and efficacy results, starting deferasirox at 10 mg/kg/day appears to be most appropriate for further study in this patient population. (Hepatology 2010) PMID:20814896

Ten‐Year Blood Pressure Trajectories, Cardiovascular Mortality, and Life Years Lost in 2 Extinction Cohorts: the Minnesota Business and Professional Men Study and the Zutphen Study

PubMed Central

Tielemans, Susanne M. A. J.; Geleijnse, Johanna M.; Menotti, Alessandro; Boshuizen, Hendriek C.; Soedamah‐Muthu, Sabita S.; Jacobs, David R.; Blackburn, Henry; Kromhout, Daan

2015-01-01

Background Blood pressure (BP) trajectories derived from measurements repeated over years have low measurement error and may improve cardiovascular disease prediction compared to single, average, and usual BP (single BP adjusted for regression dilution). We characterized 10‐year BP trajectories and examined their association with cardiovascular mortality, all‐cause mortality, and life years lost. Methods and Results Data from 2 prospective and nearly extinct cohorts of middle‐aged men—the Minnesota Business and Professional Men Study (n=261) and the Zutphen Study (n=632)—were used. BP was measured annually during 1947–1957 in Minnesota and 1960–1970 in Zutphen. BP trajectories were identified by latent mixture modeling. Cox proportional hazards and linear regression models examined BP trajectories with cardiovascular mortality, all‐cause mortality, and life years lost. Associations were adjusted for age, serum cholesterol, smoking, and diabetes mellitus. Mean initial age was about 50 years in both cohorts. After 10 years of BP measurements, men were followed until death on average 20 years later. All Minnesota men and 98% of Zutphen men died. Four BP trajectories were identified, in which mean systolic BP increased by 5 to 49 mm Hg in Minnesota and 5 to 20 mm Hg in Zutphen between age 50 and 60. The third systolic BP trajectories were associated with 2 to 4 times higher cardiovascular mortality risk, 2 times higher all‐cause mortality risk, and 4 to 8 life years lost, compared to the first trajectory. Conclusions Ten‐year BP trajectories were the strongest predictors, among different BP measures, of cardiovascular mortality, all‐cause mortality, and life years lost in Minnesota. However, average BP was the strongest predictor in Zutphen. PMID:25753924

Clinical characteristics of RA patients with secondary SS and association with joint damage.

PubMed

Brown, Lindsay E; Frits, Michelle L; Iannaccone, Christine K; Weinblatt, Michael E; Shadick, Nancy A; Liao, Katherine P

2015-05-01

Secondary SS (sSS) is a common extra-articular manifestation of RA. There are conflicting data regarding the association of sSS with worse joint damage. This study aims to characterize sSS patients in an RA cohort and study the association between sSS and joint damage. We conducted a cross-sectional study of RA patients with ≥1 year of follow-up at a large academic centre. Subjects with co-morbid diseases that can also result in sicca symptoms were excluded from the analysis. Subjects were considered to have sSS if they were reported as having sSS by their rheumatologist at recruitment into the cohort and had the diagnosis confirmed by chart review. The primary outcome was Sharp score using bilateral hand radiographs at recruitment. We constructed a linear regression model to determine the association of sSS status and Sharp score adjusted by age, gender, disease duration and ACPA and RF status. We studied 829 RA subjects, mean age 57 years, 83% female, mean RA duration 13 years, 74% seropositive; 85 subjects (10.3%) had sSS. We observed a female predominance (95.3%), longer mean disease duration (16.9 years) and higher frequency of RF or ACPA positive among patients with sSS and RA. Having sSS at baseline was associated with higher Sharp scores (P = 0.03), independent of age, gender, RA disease duration and seropositive disease. In our RA cohort, RA subjects with sSS had worse joint damage, suggesting that sSS is a marker of more aggressive disease. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Japan Diabetic Nephropathy Cohort Study: study design, methods, and implementation.

PubMed

Furuichi, Kengo; Shimizu, Miho; Toyama, Tadashi; Koya, Daisuke; Koshino, Yoshitaka; Abe, Hideharu; Mori, Kiyoshi; Satoh, Hiroaki; Imanishi, Masahito; Iwano, Masayuki; Yamauchi, Hiroyuki; Kusano, Eiji; Fujimoto, Shouichi; Suzuki, Yoshiki; Okuda, Seiya; Kitagawa, Kiyoki; Iwata, Yasunori; Kaneko, Shuichi; Nishi, Shinichi; Yokoyama, Hitoshi; Ueda, Yoshihiko; Haneda, Masakazu; Makino, Hirofumi; Wada, Takashi

2013-12-01

Diabetic nephropathy, leading to end-stage renal disease, has a considerable impact on public health and the social economy. However, there are few national registries of diabetic nephropathy in Japan. The aims of this prospective cohort study are to obtain clinical data and urine samples for revising the clinical staging of diabetic nephropathy, and developing new diagnostic markers for early diabetic nephropathy. The Japanese Society of Nephrology established a nationwide, web-based, and prospective registry system. On the system, there are two basic registries; the Japan Renal Biopsy Registry (JRBR), and the Japan Kidney Disease Registry (JKDR). In addition to the two basic registries, we established a new prospective registry to the system; the Japan Diabetic Nephropathy Cohort Study (JDNCS), which collected physical and laboratory data. We analyzed the data of 321 participants (106 female, 215 male; average age 65 years) in the JDNCS. Systolic and diastolic blood pressure was 130.1 and 72.3 mmHg, respectively. Median estimated glomerular filtration rate (eGFR) was 33.3 ml/min/1.73 m(2). Proteinuria was 1.8 g/gCr, and serum levels of albumin were 3.6 g/dl. The majority of the JDNCS patients presented with preserved eGFR and low albuminuria or low eGFR and advanced proteinuria. In the JRBR and JKDR registries, 484 and 125 participants, respectively, were enrolled as having diabetes mellitus. In comparison with the JRBR and JKDR registries, the JDNCS was characterized by diabetic patients presenting with low proteinuria with moderately preserved eGFR. There are few national registries of diabetic nephropathy to evaluate prognosis in Japan. Future analysis of the JDNCS will provide clinical insights into the epidemiology and renal and cardiovascular outcomes of type 2 diabetic patients in Japan.

A Prospective Cohort Study of Periodontal Disease Measures and Cardiovascular Disease Markers in HIV-Infected Adults

PubMed Central

Babineau, Denise C.; Demko, Catherine A.; Lederman, Michael M.; Wang, Xuelei; Toossi, Zahra; Weinberg, Aaron; Rodriguez, Benigno

2011-01-01

Abstract The determinants of HIV-associated cardiovascular disease (CVD) are not well understood. Periodontal disease (PD) has been linked to CVD but this connection has not been examined in HIV infection. We followed a cohort of HIV-infected adults to ascertain whether PD was associated with carotid artery intima media thickness (IMT) and brachial artery flow-mediated dilation (FMD). We performed a longitudinal observational study of HIV-infected adults on HAART for <2 years with no known heart disease. PD was characterized clinically and microbiologically. Cardiovascular disease was assessed by IMT/FMD. Linear mixed models assessed cross-sectional and longitudinal associations between PD and FMD/IMT. Forty three HIV+ adults completed a median of 24 (6–44) months on the study. Defining delta to be the change in a variable between baseline and a follow-up time, longitudinally, on average and after adjusting for change in time, CVD-specific and HIV-specific potential confounding covariates, a 1-log10 increase in delta Porphyromonas gingivalis was associated with a 0.013 mm increase in delta IMT (95% CI: 0.0006–0.0262; p=0.04). After adjusting for the same potential confounding covariates, a 10% increase in delta gingival recession was associated with a 2.3% increase in delta FMD (95% CI: 0.4–4.2; p=0.03). In a cohort of HIV-infected adults, an increase in subgingival Porphyromonas gingivalis, a known periodontal pathogen, was significantly associated with longitudinal increases in IMT, while increased gingival recession, which herein may represent PD resolution, was significantly associated with longitudinal improvement in FMD. In the context of HIV infection, PD may contribute to CVD risk. Intervention studies treating PD may help clarify this association. PMID:21443451

Cardiovascular disease risk factors in relation to suicide mortality in Asia: prospective cohort study of over one million Korean men and women

PubMed Central

Jee, Sun Ha; Kivimaki, Mika; Kang, Hee-Cheol; Park, Il Su; Samet, Jonathan M.; Batty, G. David

2011-01-01

Aims A potential role for cardiovascular disease (CVD) risk factors in the aetiology of suicide has not been comprehensively examined. In addition to being small in scale and poorly characterized, existing studies very rarely sample Asian populations in whom risk factor–suicide relationships may plausibly differ to Caucasian groups. We examined the association between a series of CVD risk factors and future mortality from suicide. Methods and results The Korean Cancer Prevention Study is a prospective cohort study comprising 1 234 927 individuals (445 022 women) aged 30–95 years with extensive measurement of established CVD risk factors at baseline and subsequent mortality surveillance. Fourteen years of follow-up gave rise to 472 deaths (389 in men and 83 in women) from suicide. After adjustment for a range of covariates, in men, smoking hazard ratio; 95% CI: (current vs. never: 1.69; 1.27, 2.24), alcohol intake (1–24 g/day vs. none: 1.29; 1.00, 1.66), blood cholesterol (≥240 vs. <200 mg/dL: 0.54; 0.36, 0.80), body mass index (underweight vs. normal weight: 2.08; 1.26, 3.45), stature [quartile 1(lowest) vs. 4: 1.68; 1.23, 2.30], socioeconomic status [quartile 1(lowest) vs. 4: 1.65; 1.21, 2.24], and martial status (unmarried vs. other: 1.60; 0.83, 3.06) were related to suicide mortality risk. These associations were generally apparent in women, although of lower magnitude. Exercise and blood pressure were not associated with completed suicide. Conclusion In this cohort of Korean men and women, a series of CVD risk factors were associated with an elevated risk of future suicide mortality. PMID:21911340

A comparison of the results of prospective and retrospective cohort studies in the field of digestive surgery.

PubMed

Ukai, Tomohiko; Shikata, Satoru; Nakayama, Takeo; Takemura, Yousuke C

2017-07-01

We compared the results of prospective and retrospective cohort studies in the field of digestive surgery to clarify whether the results of prospective cohort studies were more similar to those of randomized controlled trials (RCTs). We conducted a secondary analysis of the results to compare the results of RCTs with those of cohort studies in meta-analyses of 18 digestive surgical topics. The data from the prospective and retrospective cohort studies were combined. The summary estimates of each design were compared with those of RCTs. We used the Z score to investigate discrepancies. Twenty-nine outcomes of 11 topics were investigated in 289 cohort studies (prospective, n = 69; retrospective, n = 220). These were compared with the outcomes of 123 RCTs. In comparison to retrospective studies, the summary estimates of the prospective cohort studies were more similar to those of the RCTs [19/29 (prospective) vs. 10/29 (retrospective), P = 0.035). Five of the 29 outcomes of prospective studies and 6 of 29 outcomes of retrospective studies (P = 0.99) showed significant discrepancies in comparison to RCTs. In the digestive surgical field, the results of prospective cohort studies tended to be more similar to those of RCTs than retrospective studies; however, there were no significant discrepancies between the two types of cohort study.

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.

[Design and implementation of the ELSA-Brasil biobank: a prospective study in a Brazilian population].

PubMed

Pereira, Alexandre C; Bensenor, Isabela M; Fedeli, Ligia M; Castilhos, Cristina; Vidigal, Pedro G; Maniero, Viviane; Leite, Claudia M; Pimentel, Robercia A; Duncan, Bruce B; Mill, Jose Geraldo; Lotufo, Paulo A

2013-06-01

The Brazilian Longitudinal Study for Adult Health (ELSA-Brasil) is a multicenter prospective cohort of civil servants designed to assess the determinants of chronic diseases, especially cardiovascular diseases and type 2 diabetes. The present article describes the main design and implementation points of the ELSA-Brasil biobank project. Economic, political, logistical and technological aspects of this study are characterized. Additionally, it discusses the final biorepository protocol and the facilities implemented to achieve this objective. The design and implementation process of the ELSA-Brasil biobank took three years to be performed. Both the central and local biobanks were built according to the best biorepository techniques, using different technological solutions for the distinct needs expected in this study.

Sciatic Nerve Injury After Proximal Hamstring Avulsion and Repair.

PubMed

Wilson, Thomas J; Spinner, Robert J; Mohan, Rohith; Gibbs, Christopher M; Krych, Aaron J

2017-07-01

Muscle bellies of the hamstring muscles are intimately associated with the sciatic nerve, putting the sciatic nerve at risk of injury associated with proximal hamstring avulsion. There are few data informing the magnitude of this risk, identifying risk factors for neurologic injury, or determining neurologic outcomes in patients with distal sciatic symptoms after surgery. To characterize the frequency and nature of sciatic nerve injury and distal sciatic nerve-related symptoms after proximal hamstring avulsion and to characterize the influence of surgery on these symptoms. Cohort study; Level of evidence, 3. This was a retrospective review of patients with proximal partial or complete hamstring avulsion. The outcome of interest was neurologic symptoms referable to the sciatic nerve distribution below the knee. Neurologic symptoms in operative patients were compared pre- and postoperatively. The cohort consisted of 162 patients: 67 (41.4%) operative and 95 (58.6%) nonoperative. Sciatic nerve-related symptoms were present in 22 operative and 23 nonoperative patients, for a total of 45 (27.8%) patients (8 [4.9%] motor deficits, 11 [6.8%] sensory deficits, and 36 [22.2%] with neuropathic pain). Among the operative cohort, 3 of 3 (100.0%) patients showed improvement in their motor deficit postoperatively, 3 of 4 (75.0%) patients' sensory symptoms improved, and 17 of 19 (89.5%) patients had improvement in pain. A new or worsening deficit occurred in 5 (7.5%) patients postoperatively (2 [3.1%] motor deficits, 1 [1.5%] sensory deficit, and 3 [4.5%] with new pain). Predictors of operative intervention included lower age (odds ratio [OR], 0.952; 95% CI, 0.921-0.982; P = .001) and complete avulsion (OR, 10.292; 95% CI, 2.526-72.232; P < .001). Presence of neurologic deficit was not predictive. Sciatic nerve-related symptoms after proximal hamstring avulsion are underrecognized. Currently, neurologic symptoms are not considered when determining whether to pursue operative intervention. Given the high likelihood of improvement with surgical treatment, neurologic symptoms should be considered when making a decision regarding operative treatment.

Distinctive Risk Factors and Phenotype of Younger Patients With Resistant Hypertension: Age Is Relevant.

PubMed

Ghazi, Lama; Oparil, Suzanne; Calhoun, David A; Lin, Chee Paul; Dudenbostel, Tanja

2017-05-01

Resistant hypertension, defined as blood pressure >140/90 mm Hg despite using ≥3 antihypertensive medications, is a well-recognized clinical entity. Patients with resistant hypertension are at an increased risk of cardiovascular disease compared with those with more easily controlled hypertension. Coronary heart disease mortality rates of younger adults are stagnating or on the rise. The purpose of our study was to characterize the phenotype and risk factors of younger patients with resistant hypertension, given the dearth of data on cardiovascular risk profile in this cohort. We conducted a cross-sectional analysis with predefined age groups of a large, ethnically diverse cohort of 2170 patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. Patients (n=2068) met the inclusion criteria and were classified by age groups, that is, ≤40 years (12.7% of total cohort), 41 to 55 years (32.1%), 56 to 70 years (36.1%), and ≥71 years (19.1%). Patients aged ≤40 years compared with those aged ≥71 years had significantly earlier onset of hypertension (24.7±7.4 versus 55.0±14.1 years; P <0.0001), higher rates of obesity (53.4% versus 26.9%; P <0.0001), and significantly higher levels of plasma aldosterone (11.3±9.8 versus 8.9±7.4 ng/dL; P =0.005), plasma renin activity (4.9±10.2 versus 2.5±5.0 ng/mL per hour; P =0.001), 24-hour urinary aldosterone (13.4±10.0 versus 8.2±6.2 µg/24 h; P <0.0001), and sodium excretion (195.9±92.0 versus 146.8±67.1 mEq/24 h; P <0.0001). Among patients with resistant hypertension, younger individuals have a distinct phenotype characterized by overlapping risk factors and comorbidities, including obesity, high aldosterone, and high dietary sodium intake compared with elderly. © 2017 American Heart Association, Inc.

AGE IS RELEVANT: DISTINCTIVE RISK FACTORS AND PHENOTYPE OF YOUNGER PATIENTS WITH RESISTANT HYPERTENSION

PubMed Central

Ghazi, Lama; Oparil, Suzanne; Calhoun, David A.; Lin, Chee Paul; Dudenbostel, Tanja

2017-01-01

Resistant hypertension, defined as blood pressure >140/90 mmHg despite using ≥3 antihypertensive medications, is a well-recognized clinical entity. Patients with resistant hypertension are at an increased risk of cardiovascular disease compared with those with more easily controlled hypertension. Coronary heart disease mortality rates of younger adults are stagnating or on the rise. The purpose of our study was to characterize the phenotype and risk factors of younger patients with resistant hypertension given the dearth of data on cardiovascular risk profile in this cohort. We conducted a cross sectional analysis with predefined age groups of a large, ethnically diverse cohort of 2170 patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. 2068 patients met the inclusion criteria and were classified by age groups, i.e. ≤40 yrs (12.7 % of total cohort), 41–55 yrs (32.1%), 56–70 yrs (36.1%) and ≥71 yrs (19.1%). Patients ≤40 yrs of age compared with ≥71 yrs, had significantly earlier onset of HTN (24.7±7.4vs 55.0±14.1 yrs, p<0.0001), higher rates of obesity (53.4% vs 26.9%, p<0.0001), and significantly higher levels of plasma aldosterone (11.3±9.8 vs 8.9±7.4 ng/dl, p=0.005), plasma renin activity (4.9±10.2 vs 2.5±5.0 ng/ml/hr, p=0.001), and 24-hr urinary aldosterone (13.4±10.0 vs 8.2±6.2 μg/24hr, p<0.0001) and sodium excretion (195.9±92.0 vs 146.8±67.1 mEq/24hr, p<0.0001). Among patients with resistant hypertension, younger individuals have a distinct phenotype characterized by overlapping risk factors and comorbidities, including obesity, high aldosterone and high dietary sodium intake compared to elderly. PMID:28348010

Clinical associations of proinflammatory cytokines, oxidative biomarkers and vitamin D levels in systemic lupus erythematosus.

PubMed

Willis, R; Smikle, M; DeCeulaer, K; Romay-Penabad, Z; Papalardo, E; Jajoria, P; Harper, B; Murthy, V; Petri, M; Gonzalez, E B

2017-12-01

Background The abnormal biological activity of cytokines plays an important role in the pathophysiology of both systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Several studies have highlighted the association of vitamin D and certain pro-inflammatory cytokines with disease activity in SLE. However, there are limited data on the association of vitamin D and antiphospholipid antibodies (aPL) with various proinflammatory biomarkers in these patients and their relative impact on clinical outcomes. Methods The serum levels of several aPL, 25-hydroxy-vitamin D, pro-inflammatory cytokines including IFNα, IL-1β, IL-6, IL-8, IP10, sCD40L, TNFα and VEGF were measured in 312 SLE patients from the Jamaican ( n = 45) and Hopkins ( n = 267) lupus cohorts using commercial Milliplex and ELISA assays. Oxidized LDL/β2glycoprotein antigenic complexes (oxLβ2Ag) and their associated antibodies were also measured in the Jamaican cohort. Healthy controls for oxidative marker and cytokine testing were used. Results Abnormally low vitamin D levels were present in 61.4% and 73.3% of Hopkins and Jamaican SLE patients, respectively. Median concentrations of IP10, TNFα, sCD40L and VEGF were elevated in both cohorts, oxLβ2Ag and IL-6 were elevated in the Jamaican cohort, and IFNα, IL-1β and IL-8 were the same or lower in both cohorts compared to controls. IP10 and VEGF were independent predictors of disease activity, aPL, IP10 and IL-6 were independent predictors of thrombosis and IL-8, and low vitamin D were independent predictors of pregnancy morbidity despite there being no association of vitamin D with pro-inflammatory cytokines. Conclusions Our results indicate that aPL-mediated pro-inflammatory cytokine production is likely a major mechanism of thrombus development in SLE patients. We provide presumptive evidence of the role IL-8 and hypovitaminosis D play in obstetric pathology in SLE but further studies are required to characterize the subtle complexities of vitamin D's relationship with cytokine production and disease activity in these patients.

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

PubMed

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

2009-01-01

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

Water and sewage systems, socio-demographics, and duration of residence associated with endemic intestinal infectious diseases: A cohort study

PubMed Central

2010-01-01

Background Studies of water-related gastrointestinal infections are usually directed at outbreaks. Few have examined endemic illness or compared rates across different water supply and sewage disposal systems. We conducted a cohort study of physician visits and hospitalizations for endemic intestinal infectious diseases in a mixed rural and urban community near Vancouver, Canada, with varied and well-characterized water and sewage systems. Methods Cohort members and their disease events were defined via universal health insurance data from 1995 through 2003. Environmental data were derived from municipal, provincial, and federal government sources. Logistic regression was used to examine associations between disease events and water and sewage systems, socio-demographic characteristics, and temporal factors. Results The cohort included 126,499 individuals and approximately 190,000,000 person-days. Crude incidence rates were 1,353 physician visits and 33.8 hospitalizations for intestinal infectious diseases per 100,000 person-years. Water supply chlorination was associated with reduced physician visit incidence (OR: 0.92, 95% CI 0.85-1.0). Two water systems with the highest proportions of surface water had increased incidence (ORs: 1.57, 95% CI 1.39-1.78; and 1.45, 95% CI 1.28-1.64). Private well water and well depth were not associated with increased risk, likely because of residents' awareness of and attention to water quality. There was increased crude incidence with increasing precipitation in the population served by surface water supplies, but this trend did not remain with adjustment for other variables. Municipal sewer systems were associated with increased risk (OR: 1.26, 95% CI 1.14-1.38). Most socio-demographic variables had predicted associations with risk: higher rates in females, in the very young and the elderly, and in residents of low income areas. Increased duration of area residence was associated with reduced risk (OR, duration ≥ 6 years: 0.69, 95% CI 0.60-0.80 vs. < 1 year: 1.16, 95% CI 1.03-1.30). Conclusions This large cohort study, with objective data on exposures and outcomes, demonstrated associations between endemic infectious intestinal diseases and factors related to water supply, sewage disposal, socio-demographics, and duration of residency. The results did not always follow prior expectations based on studies examining outbreaks and single systems, and underscore the importance of studying factors associated with endemic disease across water and sewage system types. PMID:21162734

Temporal trends in compliance with appropriateness criteria for stress single-photon emission computed tomography sestamibi studies in an academic medical center.

PubMed

Gibbons, Raymond J; Askew, J Wells; Hodge, David; Miller, Todd D

2010-03-01

The purpose of this study was to apply published appropriateness criteria for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in a single academic medical center to determine if the percentage of inappropriate studies was changing over time. In a previous study, we applied the American College of Cardiology Foundation/American Society of Nuclear Cardiology (ASNC) appropriateness criteria for stress SPECT MPI and reported that 14% of stress SPECT studies were performed for inappropriate reasons. Using similar methodology, we retrospectively examined 284 patients who underwent stress SPECT MPI in October 2006 and compared the findings to the previous cohort of 284 patients who underwent stress SPECT MPI in May 2005. The indications for testing in the 2 cohorts were very similar. The overall level of agreement in characterizing categories of appropriateness between 2 experienced cardiovascular nurse abstractors was good (kappa = 0.68), which represented an improvement from our previous study (kappa = 0.56). There was a significant change between May 2005 and October 2006 in the overall classification of categories for appropriateness (P = .024 by chi(2) statistic). There were modest, but insignificant, increases in the number of patients who were unclassified (15% in the current study vs 11% previously), appropriate (66% vs 64%), and uncertain (12% vs 11%). Only 7% of the studies in the current study were inappropriate, which represented a significant (P = .004) decrease from the 14% reported in the 2005 cohort. In the absence of any specific intervention, there was a significant change in the overall classification of SPECT appropriateness in an academic medical center over 17 months. The only significant difference in individual categories was a decrease in inappropriate studies. Additional measurements over time will be required to determine if this trend is sustainable or generalizable.

An Historical Framework for Cohort Differences in Intelligence

PubMed Central

Schaie, K. Warner; Willis, Sherry L.; Pennak, Sara

2006-01-01

This article reviews key issues regarding the controversy on the direction and magnitude of cohort differences in intelligence. Data from the Seattle Longitudinal Study (SLS) illustrate why differences must be studied across multiple cohorts and multiple chronological ages. Differential cohort patterns for multiple dimensions of intelligence are described. A conceptual framework is suggested for the identification of historical influences important for developmental study of cohort differences. PMID:16858496

Body mass index and all-cause mortality among older adults

USDA-ARS?s Scientific Manuscript database

Objective: To examine the association between baseline body mass index (BMI, kg/m2) and all-cause mortality in a well-characterized cohort of older persons. Methods: The association between BMI (both as a categorical and continuous variable) and all-cause mortality was investigated using 4,565 Geisi...

The People Unite: Learning Meaningful Civics Online

ERIC Educational Resources Information Center

Pitts, Annette Boyd; Dziuban, Charles; Cornett, Jeffrey W.

2011-01-01

Throughout the world, today's students are being characterized as digital natives, the "net generation." This twenty-first-century student cohort is adept at multi-tasking and at using a variety of tools and resources including electronic search engines, blogs, wikis, visual images, videos, gaming platforms, and social networking.…

Rumen bacterial community structure impacts feed efficiency in beef cattle

USDA-ARS?s Scientific Manuscript database

The importance of the rumen microbiota on nutrient cycling to the animal is well recognized; however, our understanding of the influence of the rumen microbiome composition on feed efficiency is limited. The rumen microbiomes of two large animal cohorts (125 heifers and 122 steers) were characterize...

Association of Colecalciferol, Ferritin, and Anemia among Pregnant Women: Result from Cohort Study on Vitamin D Status and Its Impact during Pregnancy and Childhood in Indonesia

PubMed Central

Gumilang, Lani; Irianti, Setyorini; Wirhana, Deni; Permana, Irman; Sofjan, Liza; Duhita, Hesty; Tambunan, Lies Ani; Gurnadi, Jeffry Iman; Seno, Umar; Ghrahani, Reni; Indrati, Agnes Rengga; Sribudiani, Yunia; Yuniati, Tetty; Setiabudiawan, Budi

2018-01-01

Studies had shown that iron-cycling was disturbed by inflammatory process through the role of hepcidin. Pregnancy is characterized by shifts of interleukin. Our objective was to determine if 25(OH) vitamin D (colecalciferol) status was associated with ferritin, anemia, and its changes during pregnancy. Method. A cohort study was done in 4 cities in West Java, Indonesia, beginning in July 2016. Subjects were followed up until third trimester. Examinations included were maternal ferritin, colecalciferol, and haemoglobin level. Result. 191 (95.5%) subjects had low colecalciferol, and 151 (75.5%) among them were at deficient state. Anemia is found in 15 (7.5%) subjects, much lower than previous report. Proportion of anemia increased by trimester among women with colecalciferol deficiency. Ferritin status and prepregnancy body mass index in the first trimester were correlated with anemia (r = 0.147, p = 0.038 and r = −0.56, p = 0.03). Anemia in the second trimester was strongly correlated with anemia in the third trimester (r = 0.676, p < 0.01). Conclusion. Our study showed that the state of colecalciferol was not associated with either ferritin state or anemia, but proportion of anemia tends to increase by trimester in the colecalciferol deficient subjects. PMID:29888000

Multidisciplinary design and analytic approaches to advance prospective research on the multilevel determinants of child health.

PubMed

Johnson, Sara B; Little, Todd D; Masyn, Katherine; Mehta, Paras D; Ghazarian, Sharon R

2017-06-01

Characterizing the determinants of child health and development over time, and identifying the mechanisms by which these determinants operate, is a research priority. The growth of precision medicine has increased awareness and refinement of conceptual frameworks, data management systems, and analytic methods for multilevel data. This article reviews key methodological challenges in cohort studies designed to investigate multilevel influences on child health and strategies to address them. We review and summarize methodological challenges that could undermine prospective studies of the multilevel determinants of child health and ways to address them, borrowing approaches from the social and behavioral sciences. Nested data, variation in intervals of data collection and assessment, missing data, construct measurement across development and reporters, and unobserved population heterogeneity pose challenges in prospective multilevel cohort studies with children. We discuss innovations in missing data, innovations in person-oriented analyses, and innovations in multilevel modeling to address these challenges. Study design and analytic approaches that facilitate the integration across multiple levels, and that account for changes in people and the multiple, dynamic, nested systems in which they participate over time, are crucial to fully realize the promise of precision medicine for children and adolescents. Copyright © 2017 Elsevier Inc. All rights reserved.

Polycystic ovary syndrome and hyperglycaemia in pregnancy. A narrative review and results from a prospective Danish cohort study.

PubMed

Palm, Camilla Viola Buskbjerg; Glintborg, Dorte; Kyhl, Henriette Boye; McIntyre, H David; Jensen, Richard Christian; Jensen, Tina Kold; Jensen, Dorte Møller; Andersen, Marianne

2018-04-22

Insulin resistance is common in polycystic ovary syndrome (PCOS). PCOS may be associated with increased risk of gestational diabetes mellitus (GDM). To (1) review literature regarding PCOS and hyperglycaemia in pregnancy and (2) present original data from Odense Child Cohort (OCC) regarding GDM in PCOS. Literature search including original studies from 2000-18. OCC included 2548 pregnant women, 9.5% (n = 241) had PCOS. Fasting plasma glucose was measured in 1519 and 659 oral glucose tolerance tests were performed (with risk factor for GDM, n = 384, without risk factors, n = 275), applying two different GDM criteria. 30 studies were eligible using 12 different sets of diagnostic criteria for GDM. Ten studies included n > 50, control group, assessment of GDM and BMI. Results were not uniform, but supported that higher BMI, higher age, Asian ethnicity, and fertility treatment increased the risk of GDM in PCOS. In OCC, women with PCOS and controls had similar prevalences of GDM independent of different sets of criteria for GDM. PCOS may not be an individual risk factor for GDM. Pregnancies in PCOS are characterized by factors known to increase risk of GDM, especially high BMI and fertility treatment. Copyright © 2018. Published by Elsevier B.V.

STATUS REPORT, BEGIN TO DEVELOP COMPLETE OPERATIONS MANUALS FOR THE COHORT: PREPARE TO IMPLEMENT A COHORT STUDY OF CHILDREN'S ENVIRONMENTAL HEALTH

EPA Science Inventory

As a precursor to the National Children's Study (NCS), the North Carolina Cohort Study (NC Cohort Study) will provide the opportunity to field test procedures to better inform the implementation of the NCS. In order to test some of the study hypotheses, it will be important to ob...

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

Child Adjustment and Parent Functioning: Considering the Role of Child Driven Effects

PubMed Central

Yan, Ni; Ansari, Arya

2016-01-01

Based on 13,694 mother-child dyads from the Early Childhood Longitudinal Kindergarten Cohort (ECLS-K), this study examined the bidirectional relations between parental and child functioning from kindergarten through third grade. Results from the cross-lagged models demonstrated that child-driven effects co-occurred with parental effects and these effects were comparable in size. At the same time, however, results from the latent profile analysis revealed idiosyncratic patterns of parent and child functioning. Compared with children in the least optimal functioning profiles, those in the average and above average profiles elicited greater improvements in parents’ functioning over time. Although children characterized by poor academic performance at kindergarten appeared to precede parents characterized by harsh parenting at third grade, there was a threshold in the evolving strength of the overall child-driven effects. Taken together, the results from this study underscore the importance of considering reciprocal processes in the parent-child dynamic while also underscoring individual differences in these processes across the early to middle childhood years. PMID:26866838

Molecular profiling of multiple myeloma: from gene expression analysis to next-generation sequencing.

PubMed

Agnelli, Luca; Tassone, Pierfrancesco; Neri, Antonino

2013-06-01

Multiple myeloma is a fatal malignant proliferation of clonal bone marrow Ig-secreting plasma cells, characterized by wide clinical, biological, and molecular heterogeneity. Herein, global gene and microRNA expression, genome-wide DNA profilings, and next-generation sequencing technology used to investigate the genomic alterations underlying the bio-clinical heterogeneity in multiple myeloma are discussed. High-throughput technologies have undoubtedly allowed a better comprehension of the molecular basis of the disease, a fine stratification, and early identification of high-risk patients, and have provided insights toward targeted therapy studies. However, such technologies are at risk of being affected by laboratory- or cohort-specific biases, and are moreover influenced by high number of expected false positives. This aspect has a major weight in myeloma, which is characterized by large molecular heterogeneity. Therefore, meta-analysis as well as multiple approaches are desirable if not mandatory to validate the results obtained, in line with commonly accepted recommendation for tumor diagnostic/prognostic biomarker studies.

Characterization of children hospitalized with traumatic brain injuries after building falls.

PubMed

Loftus, Kirsten V; Rhine, Tara; Wade, Shari L; Pomerantz, Wendy J

2018-04-10

Unintentional falls cause a substantial proportion of pediatric traumatic brain injury (TBI), with building falls carrying particularly high risk for morbidity and mortality. The cohort of children sustaining building fall-related TBI has not been well-examined. We sought to characterize children hospitalized with building fall-related TBIs and evaluate if specific factors distinguished these children from children hospitalized with TBI due to other fall mechanisms. We secondarily assessed if TBI severity among children injured due to a building fall varied between children from urban versus non-urban areas. This was a secondary analysis of the Pediatric Health Information System (PHIS), an administrative database from pediatric hospitals. We identified children < 15 years old, hospitalized between 2009 and 2014, with an associated TBI-related diagnosis due to a fall as determined by International Classification of Diseases, Clinical Modification, Ninth revision (ICD9-CM) diagnosis codes. Urban versus non-urban status was determined using PHIS-assigned Rural-Urban Commuting Area codes. Injury severity (i.e. Injury Severity Score (ISS) and head Abbreviated Injury Scale (AIS) score) were calculated. Head AIS scores were dichotomized into minor/moderate (1-2) and serious/severe (3-6) for analysis. Frequencies, descriptive statistics, Chi-square analysis, and Mann-Whitney U analysis characterized populations and determined group differences. The study cohort included 23,813 children, of whom 933 (3.9%) fell from buildings. Within the building fall cohort, 707 (75.8%) resided in urban areas, 619 (66.3%) were male, 513 (55.0%) were white, and 528 (56.6%) had government insurance; the mean age was 3.8 years (SD 2.9). There was a larger proportion of children with serious/severe TBI among those injured from building falls relative to other falls (63.4% vs 53.9%, p <  0.01). Among children injured from building falls, those from non-urban areas were more likely to sustain a serious/severe TBI relative to urban children (58.9% vs 53.6%, p <  0.01). Children hospitalized following buildings falls with TBI sustained more severe injuries relative to other fall types. Although a majority of children hospitalized with building fall related-TBIs were from urban areas, those from non-urban areas frequently sustained serious head injuries. Future research should target expanding prevention efforts to include non-urban areas.

Needle age and season influence photosynthetic temperature response and total annual carbon uptake in mature Picea mariana trees

DOE PAGES

Jensen, Anna M.; Warren, Jeffrey; Hanson, Paul J.; ...

2015-01-01

Using seasonal- and cohort-specific photosynthetic temperature response functions, we quantified the physiological significance of maintaining multiple foliar cohorts in mature (~40-45 year old) Picea mariana trees in an ombrotrophic Sphagnum-bog, northern Minnesota, USA. We measured photosynthetic capacity, foliar respiration (Rd), biochemistry and morphology to estimate annual carbon (C) uptake by cohort, season and canopy position. Temperature response of key photosynthetic parameters at 25 C (i.e., light-saturated rate of CO 2 assimilation (Asat), light-saturated rate of Rubisco carboxylation (Vcmax), light-saturated electron transport rate (Jmax)) were clearly dependent on season and were generally less responsive in younger needles. Temperature optimums range betweenmore » 18.7-23.7, 31.3-38.3 and 28.7-36.7 C for Asat, Vcmax and Jmax respectively. Current-year (Y0) foliage had lower photosynthetic capacities compared to one-year-old (Y1) and two-year-old (Y2) foliage. As Y0 needles matured, values of Asat, Vcmax, Jmax, foliar LMA and nitrogen increased. Values of Vcmax, Jmax and Rd were related to foliar nitrogen but only in the youngest (Y0) cohort. Foliar ontogeny affected photosynthetic capacity more than growth temperature. Morphological and physiological cohort differences were reflected by their annual contribution to modeled C uptake, with a ~36% lower estimated annual C uptake by Y0 needles (LAI 0.52 m 2m -2) compared to Y1&2 cohorts (LAI 0.67 m 2m -2). Collectively, these results illustrate the physiological and ecological significance of characterizing multiple foliar cohorts during bud break and throughout the growth season, and for cumulative C uptake model estimates.« less

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.

Characterization of European ancestry nonalcoholic fatty liver disease-associated variants in individuals of African and Hispanic descent.

PubMed

Palmer, Nicholette D; Musani, Solomon K; Yerges-Armstrong, Laura M; Feitosa, Mary F; Bielak, Lawrence F; Hernaez, Ruben; Kahali, Bratati; Carr, J Jeffrey; Harris, Tamara B; Jhun, Min A; Kardia, Sharon L R; Langefeld, Carl D; Mosley, Thomas H; Norris, Jill M; Smith, Albert V; Taylor, Herman A; Wagenknecht, Lynne E; Liu, Jiankang; Borecki, Ingrid B; Peyser, Patricia A; Speliotes, Elizabeth K

2013-09-01

Nonalcoholic fatty liver disease (NAFLD) is an obesity-related condition affecting over 50% of individuals in some populations and is expected to become the number one cause of liver disease worldwide by 2020. Common, robustly associated genetic variants in/near five genes were identified for hepatic steatosis, a quantifiable component of NAFLD, in European ancestry individuals. Here we tested whether these variants were associated with hepatic steatosis in African- and/or Hispanic-Americans and fine-mapped the observed association signals. We measured hepatic steatosis using computed tomography in five African American (n = 3,124) and one Hispanic American (n = 849) cohorts. All analyses controlled for variation in age, age(2) , gender, alcoholic drinks, and population substructure. Heritability of hepatic steatosis was estimated in three cohorts. Variants in/near PNPLA3, NCAN, LYPLAL1, GCKR, and PPP1R3B were tested for association with hepatic steatosis using a regression framework in each cohort and meta-analyzed. Fine-mapping across African American cohorts was conducted using meta-analysis. African- and Hispanic-American cohorts were 33.9/37.5% male, with average age of 58.6/42.6 years and body mass index of 31.8/28.9 kg/m(2) , respectively. Hepatic steatosis was 0.20-0.34 heritable in African- and Hispanic-American families (P < 0.02 in each cohort). Variants in or near PNPLA3, NCAN, GCKR, PPP1R3B in African Americans and PNPLA3 and PPP1R3B in Hispanic Americans were significantly associated with hepatic steatosis; however, allele frequency and effect size varied across ancestries. Fine-mapping in African Americans highlighted missense variants at PNPLA3 and GCKR and redefined the association region at LYPLAL1. Multiple genetic variants are associated with hepatic steatosis across ancestries. This explains a substantial proportion of the genetic predisposition in African- and Hispanic-Americans. Missense variants in PNPLA3 and GCKR are likely functional across multiple ancestries. © 2013 by the American Association for the Study of Liver Diseases.

Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single-arm, phase 2, multicentre study.

PubMed

McArthur, G A; Maio, M; Arance, A; Nathan, P; Blank, C; Avril, M-F; Garbe, C; Hauschild, A; Schadendorf, D; Hamid, O; Fluck, M; Thebeau, M; Schachter, J; Kefford, R; Chamberlain, M; Makrutzki, M; Robson, S; Gonzalez, R; Margolin, K

2017-03-01

Vemurafenib has shown activity in patients with BRAFV600 mutated melanoma with brain metastases (BM). This phase 2 study evaluated vemurafenib in patients with/without prior treatment for BM. Patients with BRAFV600 mutated melanoma with BM were enrolled into cohort 1 (previously untreated BM) and cohort 2 (previously treated BM) and received vemurafenib (960 mg BID) until disease progression (PD) or intolerance. Primary endpoint was best overall response rate (BORR) in the brain in cohort 1 that was evaluated using modified RECIST 1.1 criteria using lesions ≥0.5 cm to assess response. 146 patients were treated (cohort 1 n = 90; cohort 2 n = 56), 62% of whom were male. Median (range) time since diagnosis of BM: 1.0 (0-9) month in cohort 1 and 4.2 (1-68) months in cohort 2. Median duration of treatment was 4.1 months (range 0.3-34.5) in cohort 1 and 4.1 months (range 0.2-27.6) in cohort 2. Intracranial BORR in cohort 1 by an independent review committee (IRC) was 18% (2 CRs, 14 PRs). Extracranial BORR by IRC was 33% in cohort 1 and 23% in cohort 2. Median PFS (brain only, investigator-assessed) was 3.7 months (range 0.03-33.4; IQR 1.9-5.6) in cohort 1 and 4.0 months (range 0.3-27.4; IQR 2.2-7.4) in cohort 2. Median OS was 8.9 months (range 0.6-34.5; IQR 4.9-17.0) in cohort 1 and 9.6 months (range 0.7-34.3; IQR 4.5-18.4) in cohort 2. Adverse events (AEs) were similar in type, grade and frequency to other studies of single-agent vemurafenib. Grade 3/4 AEs occurred in 59 (66%) patients in cohort 1 and 36 (64%) in cohort 2. Overall, 84% of patients died during the study (86% in cohort 1 and 80% in cohort 2), mainly due to disease progression. The study demonstrates clinically meaningful response rates of melanoma BM to vemurafenib, which was well tolerated and without significant CNS toxicity. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

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

2018-06-05

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

Characteristics of Cavotricuspid Isthmus Ablation for Atrial Flutter Guided by Novel Parameters Using a Contact Force Catheter.

PubMed

Gould, Paul A; Booth, Cameron; Dauber, Kieran; Ng, Kevin; Claughton, Andrew; Kaye, Gerald C

2016-12-01

This study sought to investigate specific contact force (CF) parameters to guide cavotricuspid isthmus (CTI) ablation and compare the outcome with a historical control cohort. Patients (30) undergoing CTI ablation were enrolled prospectively in the Study cohort and compared with a retrospective Control cohort of 30 patients. Ablation in the Study cohort was performed using CF parameters >10 g and <40 g and a Force Time Integral (FTI) of 800 ± 10 g. The Control cohort underwent traditionally guided CTI ablation. Traditional parameters (electrogram and impedance change) were assessed in both cohorts. All ablations regardless of achieving targets were included in data analysis. Bidirectional CTI block was achieved in all of the Study and 27 of the Control cohort. Atrial flutter recurred in 3 (10%) patients (follow-up 564 ± 212 days) in the study cohort and in 3 (10%) patients (follow-up 804 ± 540 days) in the Control cohort. There were no major complications in either cohort. Traditional parameters correlated poorly with CF parameters. In the Study cohort, flutter recurrence was associated with significantly lower FTI and ablation duration, but was not associated with total average CF. CTI ablation can be safely performed using CF parameters guiding ablation, with similar long-term results to a historical ablation control group. Potentially CF parameters may provide adjunctive information to enable a more efficient CTI ablation. Further research is required to confirm this. © 2016 Wiley Periodicals, Inc.

Giardia: a pathogen or commensal for children in high prevalence settings?

PubMed Central

Bartelt, Luther A.

2016-01-01

Purpose of review Giardia is a common intestinal parasite worldwide, and infection can be associated with clear and sometimes persistent symptomatology. However, in children in high prevalence settings, it is not associated with or is perhaps even protective against acute diarrhea, and the association with long-term outcomes has been difficult to discern. Recent findings Recent studies have made progress in helping us disentangle this apparent paradox. First, prospective, well-characterized cohort studies have added to the data on the association between Giardia and diarrhea in these settings and have further characterized associations between Giardia infection and nutrition, gut function, and growth. Second, animal models have further characterized the host response to Giardia and helped elucidate mechanisms by which Giardia could impair child development. Finally, new work has shed light on the heterogeneity of human Giardia strains, which may both explain discrepant findings in the literature and help guide higher-resolution analyses of this pathogen in the future. Summary The true clinical impact of endemic pediatric giardiasis remains unclear, but recent prospective studies have confirmed a high prevalence of persistent, subclinical Giardia infections and associated growth shortfalls. Integrating how nutritional, microbial, metabolic, and pathogen-strain variables influence these outcomes could sharpen delineations between pathogenic and potentially beneficial attributes of this enigmatic parasite. PMID:27479025

Giardia: a pathogen or commensal for children in high-prevalence settings?

PubMed

Bartelt, Luther A; Platts-Mills, James A

2016-10-01

Giardia is a common intestinal parasite worldwide, and infection can be associated with clear and sometimes persistent symptomatology. However, in children in high-prevalence settings, it is not associated with or is perhaps even protective against acute diarrhea, and the association with long-term outcomes has been difficult to discern. Recent studies have made progress in helping us disentangle this apparent paradox. First, prospective, well-characterized cohort studies have added to the data on the association between Giardia and diarrhea in these settings and have further characterized associations between Giardia infection and nutrition, gut function, and growth. Second, animal models have further characterized the host response to Giardia and helped elucidate mechanisms by which Giardia could impair child development. Finally, new work has shed light on the heterogeneity of human Giardia strains, which may both explain discrepant findings in the literature and help guide higher-resolution analyses of this pathogen in the future. The true clinical impact of endemic pediatric giardiasis remains unclear, but recent prospective studies have confirmed a high prevalence of persistent, subclinical Giardia infections and associated growth shortfalls. Integrating how nutritional, microbial, metabolic, and pathogen-strain variables influence these outcomes could sharpen delineations between pathogenic and potentially beneficial attributes of this enigmatic parasite.

The Impact of Middle Turbinate Concha Bullosa on the Severity of Inferior Turbinate Hypertrophy in Patients with a Deviated Nasal Septum.

PubMed

Tomblinson, C M; Cheng, M-R; Lal, D; Hoxworth, J M

2016-07-01

Inferior turbinate hypertrophy and concha bullosa often occur opposite the direction of nasal septal deviation. The objective of this retrospective study was to determine whether a concha bullosa impacts inferior turbinate hypertrophy in patients who have nasal septal deviation. The electronic medical record was used to identify sinus CT scans exhibiting nasal septal deviation for 100 adult subjects without and 100 subjects with unilateral middle turbinate concha bullosa. Exclusion criteria included previous sinonasal surgery, tumor, sinusitis, septal perforation, and craniofacial trauma. Nasal septal deviation was characterized in the coronal plane by distance from the midline (severity) and height from the nasal floor. Measurement differences between sides for inferior turbinate width (overall and bone), medial mucosa, and distance to the lateral nasal wall were calculated as inferior turbinate hypertrophy indicators. The cohorts with and without concha bullosa were similarly matched for age, sex, and nasal septal deviation severity, though nasal septal deviation height was greater in the cohort with concha bullosa than in the cohort without concha bullosa (19.1 ± 4.3 mm versus 13.5 ± 4.1 mm, P < .001). Compensatory inferior turbinate hypertrophy was significantly greater in the cohort without concha bullosa than in the cohort with it as measured by side-to-side differences in turbinate overall width, bone width, and distance to the lateral nasal wall (P < .01), but not the medial mucosa. Multiple linear regression analyses found nasal septal deviation severity and height to be significant predictors of inferior turbinate hypertrophy with positive and negative relationships, respectively (P < .001). Inferior turbinate hypertrophy is directly proportional to nasal septal deviation severity and inversely proportional to nasal septal deviation height. The effect of a concha bullosa on inferior turbinate hypertrophy is primarily mediated through influence on septal morphology, because the nasal septal deviation apex tends to be positioned more superior from the nasal floor in these patients. © 2016 by American Journal of Neuroradiology.

Prognostication of patients with clear cell renal cell carcinomas based on quantification of DNA methylation levels of CpG island methylator phenotype marker genes.

PubMed

Tian, Ying; Arai, Eri; Gotoh, Masahiro; Komiyama, Motokiyo; Fujimoto, Hiroyuki; Kanai, Yae

2014-10-20

The CpG island methylator phenotype (CIMP) of clear cell renal cell carcinomas (ccRCCs) is characterized by accumulation of DNA methylation at CpG islands and poorer patient outcome. The aim of this study was to establish criteria for prognostication of patients with ccRCCs using the ccRCC-specific CIMP marker genes. DNA methylation levels at 299 CpG sites in the 14 CIMP marker genes were evaluated quantitatively in tissue specimens of 88 CIMP-negative and 14 CIMP-positive ccRCCs in a learning cohort using the MassARRAY system. An additional 100 ccRCCs were also analyzed as a validation cohort. Receiver operating characteristic curve analysis showed that area under the curve values for the 23 CpG units including the 32 CpG sites in the 7 CIMP-marker genes, i.e. FAM150A, ZNF540, ZNF671, ZNF154, PRAC, TRH and SLC13A5, for discrimination of CIMP-positive from CIMP-negative ccRCCs were larger than 0.95. Criteria combining the 23 CpG units discriminated CIMP-positive from CIMP-negative ccRCCs with 100% sensitivity and specificity in the learning cohort. Cancer-free and overall survival rates of patients with CIMP-positive ccRCCs diagnosed using the criteria combining the 23 CpG units in a validation cohort were significantly lower than those of patients with CIMP-negative ccRCCs (P = 1.41 × 10-5 and 2.43 × 10-13, respectively). Patients with CIMP-positive ccRCCs in the validation cohort had a higher likelihood of disease-related death (hazard ratio, 75.8; 95% confidence interval, 7.81 to 735; P = 1.89 × 10-4) than those with CIMP-negative ccRCCs. The established criteria are able to reproducibly diagnose CIMP-positive ccRCCs and may be useful for personalized medicine for patients with ccRCCs.

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

Phase II study of nab-paclitaxel in refractory small bowel adenocarcinoma and CpG island methylator phenotype (CIMP)-high colorectal cancer.

PubMed

Overman, M J; Adam, L; Raghav, K; Wang, J; Kee, B; Fogelman, D; Eng, C; Vilar, E; Shroff, R; Dasari, A; Wolff, R; Morris, J; Karunasena, E; Pisanic, R; Azad, N; Kopetz, S

2018-01-01

Hypermethylation of promoter CpG islands [CpG island methylator phenotype (CIMP)] represents a unique pathway for the development of colorectal cancer (CRC), characterized by lack of chromosomal instability and a low rate of adenomatous polyposis coli (APC) mutations, which have both been correlated with taxane resistance. Similarly, small bowel adenocarcinoma (SBA), a rare tumor, also has a low rate of APC mutations. This phase II study evaluated taxane sensitivity in SBA and CIMP-high CRC. The primary objective was Response Evaluation Criteria in Solid Tumors version 1.1 response rate. Eligibility included Eastern Cooperative Oncology Group performance status 0/1, refractory disease, and SBA or CIMP-high metastatic CRC. Nab-paclitaxel was initially administered at a dose of 260 mg/m2 every 3 weeks but was reduced to 220 mg/m2 owing to toxicity. A total of 21 patients with CIMP-high CRC and 13 with SBA were enrolled from November 2012 to October 2014. The efficacy-assessable population (patients who received at least three doses of the treatment) comprised 15 CIMP-high CRC patients and 10 SBA patients. Common grade 3 or 4 toxicities were fatigue (12%), neutropenia (9%), febrile neutropenia (9%), dehydration (6%), and thrombocytopenia (6%). No responses were seen in the CIMP-high CRC cohort and two partial responses were seen in the SBA cohort. Median progression-free survival was significantly greater in the SBA cohort than in the CIMP-high CRC cohort (3.2 months compared with 2.1 months, P = 0.03). Neither APC mutation status nor CHFR methylation status correlated with efficacy in the CIMP-high CRC cohort. In vivo testing of paclitaxel in an SBA patient-derived xenograft validated the activity of taxanes in this disease type. Although preclinical studies suggested taxane sensitivity was associated with chromosomal stability and wild-type APC, we found that nab-paclitaxel was inactive in CIMP-high metastatic CRC. Nab-paclitaxel may represent a novel therapeutic option for SBA. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The HIV-Brazil Cohort Study: Design, Methods and Participant Characteristics

PubMed Central

Grangeiro, Alexandre; Escuder, Maria Mercedes; Cassanote, Alex Jones Flores; Souza, Rosa Alencar; Kalichman, Artur O.; Veloso, Valdiléa; Ikeda, Maria Letícia Rodrigues; Barcellos, Nêmora Tregnago; Brites, Carlos; Tupinanbás, Unai; Lucena, Noaldo O.; da Silva, Carlos Lima; Lacerda, Heloisa Ramos; Grinsztejn, Beatriz; Castilho, Euclides Ayres

2014-01-01

Background The HIV-Brazil Cohort Study was established to analyze the effectiveness of combination antiretroviral therapy (cART) and the impact of this treatment on morbidity, quality of life (QOL) and mortality. The study design, patients’ profiles and characteristics of cART initiation between 2003 and 2010 were described. Methodology/Principal Findings Since 2003, the HIV-Brazil Cohort has been following HIV-infected adults receiving cART at 26 public health care facilities, using routine clinical care data and self-reported QOL questionnaires. When not otherwise available, data are obtained from national information systems. The main outcomes of interest are diseases related or unrelated to HIV; suppression of viral replication; adverse events; virological, clinical and immunological failures; changes in the cART; and mortality. For the 5,061 patients who started cART between 2003 and 2010, the median follow-up time was 4.1 years (IQR 2.2–5.9 years) with an 83.4% retention rate. Patient profiles were characterized by a predominance of men (male/female ratio 1.7∶1), with a mean age of 36.9 years (SD 9.9 years); 55.2% had been infected with HIV via heterosexual contact. The majority of patients (53.4%) initiated cART with a CD4+ T-cell count ≤200 cells/mm3. The medications most often used in the various treatment regimens were efavirenz (59.7%) and lopinavir/ritonavir (18.2%). The proportion of individuals achieving viral suppression within the first 12 months of cART use was 77.4% (95% CI 76.1–78.6). Nearly half (45.4%) of the patients presented HIV-related clinical manifestations after starting cART, and the AIDS mortality rate was 13.9 per 1,000 person-years. Conclusions/Significance Results from cART use in the daily practice of health services remain relatively unknown in low- and middle-income countries, and studies with the characteristics of the HIV-Brazil Cohort contribute to minimizing these shortcomings, given its scope and patient profile, which is similar to that of the AIDS epidemic in the country. PMID:24789106

Validation of the Children's Eating Behavior Questionnaire in 3 year old children of a multi-ethnic Asian population: The GUSTO cohort study.

PubMed

Quah, Phaik Ling; Cheung, Yin Bun; Pang, Wei Wei; Toh, Jia Ying; Saw, Seang-Mei; Godfrey, Keith M; Yap, Fabian; Chong, Yap Seng; Mary, Chong Foong-Fong

2017-06-01

The Children's Eating Behaviour Questionnaire (CEBQ) was developed to measure eating behaviors related to obesity risk in children. However, this questionnaire has not been validated for use in South East Asia, where parenting practices are different from those in western countries and child obesity rates are increasing. The aim of this study was to examine the validity of the CEBQ administered to mothers of children aged 3 years in Singapore. Confirmatory factor analysis (CFA) was used to examine if the original 35-item, 8-factor model was supported in our cohort. Participants were 636 mother-child dyads (mean (SD) child age = 36.7 (1.6) months), from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort in which the mothers were characterized in pregnancy and children were followed up to age 3 years. The CFA showed a poor model fit; RMSEA = 0.072 (PCLOSE<0.001), SRMR = 0.094, CFI = 0.826, and TLI = 0.805. Exploratory factor analysis revealed a 35 item, 7-factor structure (factor loadings ≥ 0.35): enjoyment of food, food fussiness, emotional overeating, desire to drink, emotional under eating, satiety responsiveness and slowness in eating. Cronbach's alpha estimates ranged from 0.70 to 0.88 for the 7 subscales. Convergent validity tests via correlation analysis revealed that emotional under eating (r = -0.14), slowness in eating (r = -0.16) and satiety responsiveness (r = -0.11) were negatively correlated with BMI z-score at 3 years, while enjoyment of food (r = 0.12) was positively correlated, p < 0.05. In conclusion, we found a revised 7-factor structure of the CEBQ more appropriate for examining eating behavior in 3 year old children in the Singapore setting. Further replication studies in a separate cohort study are warranted before further use of these factor structures generated. Copyright © 2017 Elsevier Ltd. All rights reserved.

No Evidence of a Common DNA Variant Profile Specific to World Class Endurance Athletes

PubMed Central

Wolfarth, Bernd; Wang, Guan; Sarzynski, Mark A.; Alexeev, Dmitry G.; Ahmetov, Ildus I.; Boulay, Marcel R.; Cieszczyk, Pawel; Eynon, Nir; Filipenko, Maxim L.; Garton, Fleur C.; Generozov, Edward V.; Govorun, Vadim M.; Houweling, Peter J.; Kawahara, Takashi; Kostryukova, Elena S.; Kulemin, Nickolay A.; Larin, Andrey K.; Maciejewska-Karłowska, Agnieszka; Miyachi, Motohiko; Muniesa, Carlos A.; Murakami, Haruka; Ospanova, Elena A.; Padmanabhan, Sandosh; Pavlenko, Alexander V.; Pyankova, Olga N.; Santiago, Catalina; Sawczuk, Marek; Scott, Robert A.; Uyba, Vladimir V.; Yvert, Thomas; Perusse, Louis; Ghosh, Sujoy; Rauramaa, Rainer; North, Kathryn N.; Lucia, Alejandro; Pitsiladis, Yannis; Bouchard, Claude

2016-01-01

There are strong genetic components to cardiorespiratory fitness and its response to exercise training. It would be useful to understand the differences in the genomic profile of highly trained endurance athletes of world class caliber and sedentary controls. An international consortium (GAMES) was established in order to compare elite endurance athletes and ethnicity-matched controls in a case-control study design. Genome-wide association studies were undertaken on two cohorts of elite endurance athletes and controls (GENATHLETE and Japanese endurance runners), from which a panel of 45 promising markers was identified. These markers were tested for replication in seven additional cohorts of endurance athletes and controls: from Australia, Ethiopia, Japan, Kenya, Poland, Russia and Spain. The study is based on a total of 1520 endurance athletes (835 who took part in endurance events in World Championships and/or Olympic Games) and 2760 controls. We hypothesized that world-class athletes are likely to be characterized by an even higher concentration of endurance performance alleles and we performed separate analyses on this subsample. The meta-analysis of all available studies revealed one statistically significant marker (rs558129 at GALNTL6 locus, p = 0.0002), even after correcting for multiple testing. As shown by the low heterogeneity index (I2 = 0), all eight cohorts showed the same direction of association with rs558129, even though p-values varied across the individual studies. In summary, this study did not identify a panel of genomic variants common to these elite endurance athlete groups. Since GAMES was underpowered to identify alleles with small effect sizes, some of the suggestive leads identified should be explored in expanded comparisons of world-class endurance athletes and sedentary controls and in tightly controlled exercise training studies. Such studies have the potential to illuminate the biology not only of world class endurance performance but also of compromised cardiac functions and cardiometabolic diseases. PMID:26824906

No Evidence of a Common DNA Variant Profile Specific to World Class Endurance Athletes.

PubMed

Rankinen, Tuomo; Fuku, Noriyuki; Wolfarth, Bernd; Wang, Guan; Sarzynski, Mark A; Alexeev, Dmitry G; Ahmetov, Ildus I; Boulay, Marcel R; Cieszczyk, Pawel; Eynon, Nir; Filipenko, Maxim L; Garton, Fleur C; Generozov, Edward V; Govorun, Vadim M; Houweling, Peter J; Kawahara, Takashi; Kostryukova, Elena S; Kulemin, Nickolay A; Larin, Andrey K; Maciejewska-Karłowska, Agnieszka; Miyachi, Motohiko; Muniesa, Carlos A; Murakami, Haruka; Ospanova, Elena A; Padmanabhan, Sandosh; Pavlenko, Alexander V; Pyankova, Olga N; Santiago, Catalina; Sawczuk, Marek; Scott, Robert A; Uyba, Vladimir V; Yvert, Thomas; Perusse, Louis; Ghosh, Sujoy; Rauramaa, Rainer; North, Kathryn N; Lucia, Alejandro; Pitsiladis, Yannis; Bouchard, Claude

2016-01-01

There are strong genetic components to cardiorespiratory fitness and its response to exercise training. It would be useful to understand the differences in the genomic profile of highly trained endurance athletes of world class caliber and sedentary controls. An international consortium (GAMES) was established in order to compare elite endurance athletes and ethnicity-matched controls in a case-control study design. Genome-wide association studies were undertaken on two cohorts of elite endurance athletes and controls (GENATHLETE and Japanese endurance runners), from which a panel of 45 promising markers was identified. These markers were tested for replication in seven additional cohorts of endurance athletes and controls: from Australia, Ethiopia, Japan, Kenya, Poland, Russia and Spain. The study is based on a total of 1520 endurance athletes (835 who took part in endurance events in World Championships and/or Olympic Games) and 2760 controls. We hypothesized that world-class athletes are likely to be characterized by an even higher concentration of endurance performance alleles and we performed separate analyses on this subsample. The meta-analysis of all available studies revealed one statistically significant marker (rs558129 at GALNTL6 locus, p = 0.0002), even after correcting for multiple testing. As shown by the low heterogeneity index (I2 = 0), all eight cohorts showed the same direction of association with rs558129, even though p-values varied across the individual studies. In summary, this study did not identify a panel of genomic variants common to these elite endurance athlete groups. Since GAMES was underpowered to identify alleles with small effect sizes, some of the suggestive leads identified should be explored in expanded comparisons of world-class endurance athletes and sedentary controls and in tightly controlled exercise training studies. Such studies have the potential to illuminate the biology not only of world class endurance performance but also of compromised cardiac functions and cardiometabolic diseases.

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

Safety of Outpatient Autologous Hematopoietic Cell Transplantation for Multiple Myeloma and Lymphoma

PubMed Central

Graff, Tara M.; Singavi, Arun K.; Schmidt, William; Eastwood, Daniel; Drobyski, William R.; Horowitz, Mary; Palmer, Jeanne; Pasquini, Marcelo; Rizzo, Douglas J.; Saber, Wael; Hari, Parmeswaran; Fenske, Timothy S.

2015-01-01

Autologous peripheral stem cell transplantation (AutoHCT) is commonly an inpatient procedure. However, AutoHCT is increasingly being offered on an outpatient basis. To better characterize the safety of outpatient AutoHCT, we compared the outcome of 230 patients who underwent AutoHCT on an inpatient (IP) versus outpatient (OP) basis for myeloma or lymphoma within a single transplant program. All OP transplants occurred in a cancer center day hospital. Hematopoietic recovery occurred earlier in the OP cohort, with median time to neutrophil recovery of 10 vs. 11 days (p<0.001) and median time to platelet recovery of 19 vs. 20 days (p=0.053). 51% of the OP cohort never required admission, with this percentage increasing in later years. Grade 3–4 non-hematologic toxicities occurred in 29% of both cohorts. Non-relapse mortality at one year was 0% in the OP cohort and 1.5% in the IP cohort (p=0.327). Two year progression-free survival was 62% for OP vs. 54% for IP (p=0.155). One and two year overall survival was 97% and 83% for OP vs. 91% and 80% for IP, respectively (p=0.271). We conclude that, with daily outpatient evaluation and aggressive supportive care, outpatient AutoHCT can result in excellent outcomes for myeloma and lymphoma patients. PMID:25867651

[EFFECT OF EARLY PROTEIN-CALORIE MALNUTRITION ON NUTRITIONAL STATUS AND ATTRIBUTES OF THE METABOLIC SYNDROME IN YOUNG ADULTS].

PubMed

Escaffi Fonseca, María José; Moreira Carrasco, Loreto; Rodríguez Osiac, Lorena; Pizarro Quevedo, Tito; Cavada Chacón, Gabriel; Villarroel del Pino, Luis; Salas Guzmán, Natalia; Muzzo Benavides, Santiago; Mönckeberg Barros, Fernando; Rozowski Narkunska, Jaime; Castillo Valenzuela, Oscar

2015-09-01

during recent years consistent studies have characterized the relationship between moderate and severe protein-calorie malnutrition and the appearance of non-communicable diseases in adulthood like metabolic syndrome (MS). to analyze the relationship between moderate and severe protein-calorie malnutrition during the first 1 000 days of life and the MS in a cohort of adults from Curicó, Chile. we studied 49 young adults who had suffered moderate to severe protein-calorie malnutrition during their first two years of life. Anthropometry, blood pressure measurement and laboratory tests were performed, and the burden of MS attributes was determined. the prevalence of MS was 14.3% with no significant differences by gender, showing a direct and significant association between burden of MS and body mass index, waist / height index, blood pressure, plasma levels of glucose and triglyceride, and an inverse association with HDL. systolic blood pressure and plasma level of triglyceride represented the most important risk factors for SM in this cohort. We found no association between the presence of protein-calorie malnutrition and MS. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Allelic distribution of human leucocyte antigen in historical and recently diagnosed tuberculosis patients in Southern Italy.

PubMed

Ruggiero, Giuseppina; Cosentini, Elena; Zanzi, Delia; Sanna, Veronica; Terrazzano, Giuseppe; Matarese, Giuseppe; Sanduzzi, Alessandro; Perna, Francesco; Zappacosta, Serafino

2004-03-01

This study addresses the analysis of the human leucocyte antigen (HLA) allele distribution in 54 historical and in 68 recently diagnosed tuberculosis (TB) patients. The historical cohort was characterized by the presence of large fibrocavernous lesions effectively treated with therapeutic pneumothorax during the period 1950-55. Patients and healthy controls enrolled in the study were from the Campania region of southern Italy. No significant association between HLA alleles and TB in the population of recently diagnosed TB patients was observed. On the contrary, among the historical TB patients there was a strong association with an increased frequency of the HLA-DR4 allele alone and/or in the presence of the HLA-B14 allele (P = 0.000004; Pc = 0.0008), as well as with a decreased frequency of the HLA-A2+,-B14-,DR4- allele association (P = 0.00005; Pc = 0.01). In order to exclude any interference from age-related factors, these results were confirmed by comparing the historical cohort of TB patients with an age-matched healthy control population of the same ethnic origin (P = 0.00004; Pc = 0.008; and P = 0.0001; and Pc = 0.02, respectively).

High Frequency of Tropheryma whipplei in Culture-Negative Endocarditis

PubMed Central

Geißdörfer, Walter; Moter, Annette; Loddenkemper, Christoph; Jansen, Andreas; Tandler, René; Morguet, Andreas J.; Fenollar, Florence; Raoult, Didier; Bogdan, Christian

2012-01-01

“Classical” Whipple's disease (cWD) is caused by Tropheryma whipplei and is characterized by arthropathy, weight loss, and diarrhea. T. whipplei infectious endocarditis (TWIE) is rarely reported, either in the context of cWD or as isolated TWIE without signs of systemic infection. The frequency of TWIE is unknown, and systematic studies are lacking. Here, we performed an observational cohort study on the incidence of T. whipplei infection in explanted heart valves in two German university centers. Cardiac valves from 1,135 patients were analyzed for bacterial infection using conventional culture techniques, PCR amplification of the bacterial 16S rRNA gene, and subsequent sequencing. T. whipplei-positive heart valves were confirmed by specific PCR, fluorescence in situ hybridization, immunohistochemistry, histological examination, and culture for T. whipplei. Bacterial endocarditis was diagnosed in 255 patients, with streptococci, staphylococci, and enterococci being the main pathogens. T. whipplei was the fourth most frequent pathogen, found in 16 (6.3%) cases, and clearly outnumbered Bartonella quintana, Coxiella burnetii, and members of the HACEK group (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae). In this cohort, T. whipplei was the most commonly found pathogen associated with culture-negative infective endocarditis. PMID:22135251

Methicillin-resistant Staphylococcus aureus colonization, behavioral risk factors, and skin and soft-tissue infection at an ambulatory clinic serving a large population of HIV-infected men who have sex with men.

PubMed

Szumowski, John D; Wener, Kenneth M; Gold, Howard S; Wong, Michael; Venkataraman, Lata; Runde, Carrie A; Cohen, Daniel E; Mayer, Kenneth H; Wright, Sharon B

2009-07-01

We conducted a prospective cohort study of 795 outpatients, many of whom were human immunodeficiency virus-infected men who have sex with men, to characterize risk of skin and soft-tissue infection (SSTI) associated with methicillin-resistant Staphylococcus aureus (MRSA) nares and perianal colonization. Multivariate analysis revealed that perianal colonization, drug use, and prior SSTIs were strongly associated with development of an SSTI. Of the patients who were colonized with MRSA at study entry, 36.7% developed an SSTI during the ensuing 12 months, compared with 8.1% of persons who were not colonized with MRSA.

[Methodologies of publications in the Revista de Investigación Clínica during the last 20 years].

PubMed

López-Jiménez, F; Borovoy, J

1997-01-01

To characterize the clinical research methods published in the Revista de Investigación Clínica for the past 20 years. Comparative study of methods used in the RIC articles published in 3-years periods representing three decades (1972-74, 1982-84, 1992-94). Out of 273 original papers, 218 (80%) were of clinical research. There was an increased percentage of longitudinal vs cross-sectional studies, with cohort and randomized clinical trials showing the largest increase. The total number of research manuscripts also increased. The clinical research methods of the papers in the RIC have shown an increased rate of designs with a higher scientific value.

Low prevalence of type 2 diabetes mellitus among patients with high levels of high-density lipoprotein cholesterol.

PubMed

Juren, Andrew J; Sarwal, Gautamn; Al-Sarraf, Ahmad; Vrablik, Michal; Chan, Darren; Humphries, Karin H; Frohlich, Jiri J

2013-01-01

Diabetes mellitus and low levels of high-density lipoprotein cholesterol (HDL-C) are among several known risk factors for coronary artery disease. Recent research has shown potential mechanistic links between these two diseases. The aim of our study was to characterize, by examining particular coronary artery disease risk factors, patients with extremely high and low levels of HDL-C who were referred to a prevention clinic. We compared the phenotypes of 113 patients with HDL-C levels greater than the 90th percentile with 212 patients with levels less than the 10th percentile by using a retrospective chart review. The cohort with high HDL-C had a remarkable difference in the incidence of type 2 diabetes (1.8% vs 21.7%). The high HDL-C cohort also had a greater age (52.1 years vs 46.7 years), more light or moderate alcohol consumption (70.8% vs 49.4%), more healthy diet (30.1% vs 22.4%), more light or moderate exercise (90.8% vs 52.2%), and a lower body mass index (25.2 kg/m² vs 28.1 kg/m²). Compared with the low HDL-C group--and also the general population--the high HDL-C cohort had a remarkably low prevalence of diabetes mellitus. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Expanding the phenome and variome of skeletal dysplasia.

PubMed

Maddirevula, Sateesh; Alsahli, Saud; Alhabeeb, Lamees; Patel, Nisha; Alzahrani, Fatema; Shamseldin, Hanan E; Anazi, Shams; Ewida, Nour; Alsaif, Hessa S; Mohamed, Jawahir Y; Alazami, Anas M; Ibrahim, Niema; Abdulwahab, Firdous; Hashem, Mais; Abouelhoda, Mohamed; Monies, Dorota; Al Tassan, Nada; Alshammari, Muneera; Alsagheir, Afaf; Seidahmed, Mohammed Zain; Sogati, Samira; Aglan, Mona S; Hamad, Muddathir H; Salih, Mustafa A; Hamed, Ahlam A; Alhashmi, Nadia; Nabil, Amira; Alfadli, Fatima; Abdel-Salam, Ghada M H; Alkuraya, Hisham; Peitee, Winnie Ong; Keng, W T; Qasem, Abdullah; Mushiba, Aziza M; Zaki, Maha S; Fassad, Mahmoud R; Alfadhel, Majid; Alexander, Saji; Sabr, Yasser; Temtamy, Samia; Ekbote, Alka V; Ismail, Samira; Hosny, Gamal Ahmed; Otaify, Ghada A; Amr, Khalda; Al Tala, Saeed; Khan, Arif O; Rizk, Tamer; Alaqeel, Aida; Alsiddiky, Abdulmonem; Singh, Ankur; Kapoor, Seema; Alhashem, Amal; Faqeih, Eissa; Shaheen, Ranad; Alkuraya, Fowzan S

2018-04-05

PurposeTo describe our experience with a large cohort (411 patients from 288 families) of various forms of skeletal dysplasia who were molecularly characterized.MethodsDetailed phenotyping and next-generation sequencing (panel and exome).ResultsOur analysis revealed 224 pathogenic/likely pathogenic variants (54 (24%) of which are novel) in 123 genes with established or tentative links to skeletal dysplasia. In addition, we propose 5 genes as candidate disease genes with suggestive biological links (WNT3A, SUCO, RIN1, DIP2C, and PAN2). Phenotypically, we note that our cohort spans 36 established phenotypic categories by the International Skeletal Dysplasia Nosology, as well as 18 novel skeletal dysplasia phenotypes that could not be classified under these categories, e.g., the novel C3orf17-related skeletal dysplasia. We also describe novel phenotypic aspects of well-known disease genes, e.g., PGAP3-related Toriello-Carey syndrome-like phenotype. We note a strong founder effect for many genes in our cohort, which allowed us to calculate a minimum disease burden for the autosomal recessive forms of skeletal dysplasia in our population (7.16E-04), which is much higher than the global average.ConclusionBy expanding the phenotypic, allelic, and locus heterogeneity of skeletal dysplasia in humans, we hope our study will improve the diagnostic rate of patients with these conditions.GENETICS in MEDICINE advance online publication, 5 April 2018; doi:10.1038/gim.2018.50.

Patient-shared TCRβ-CDR3 clonotypes correlate with favorable prognosis in chronic hepatitis B.

PubMed

Jiang, Qiong; Zhao, Tingting; Zheng, Wenhong; Zhou, Jijun; Wang, Haoliang; Dong, Hui; Chen, Yongwen; Tang, Xiaoqin; Liu, Cong; Ye, Lilin; Mao, Qing; Wang, Chunlin; Han, Jian; Shang, Xiaoyun; Wu, Yuzhang

2018-06-01

The presence of shared T cell clonotypes was found in several different diseases, but its relationship with the progression of disease remains unclear. By sequencing the complementary determining region 3 of T cell receptor (TCR) β chains from the purified antigen-experienced CD8 + T cells, we characterized the T cell repertoire in a prospective cohort study among 75 patients with chronic hepatitis B in China, as well as a healthy control and a validation cohort. We found that most T cell clones from patients harbored the 'patient-specific' TCR sequences. However, 'patient-shared' TCR clonotypes were also widely found, which correlated with the favorable turnover of disease. Interestingly, the frequency of the 'patient-shared' clonotypes can serve as a biomarker for favorable prognosis. Based on the clonotypes in those patients with favorable outcomes, we created a database including several clusters of protective anti-HBV CD8 + T cell clonotypes that might be a reasonable target for therapeutic vaccine development or adoptive cell transfer therapy. These findings were validated in an additional independent cohort of patients. These results suggest that the 'patient-shared' TCR clonotypes may serve as a valuable prognostic tool in the treatment of chronic hepatitis B and possibly other chronic viral diseases. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

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

PubMed

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

2013-11-01

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

Are There Subtypes of Panic Disorder? An Interpersonal Perspective

PubMed Central

Zilcha-Mano, Sigal; McCarthy, Kevin S.; Dinger, Ulrike; Chambless, Dianne L.; Milrod, Barbara L.; Kunik, Lauren; Barber, Jacques P.

2015-01-01

Objective Panic disorder (PD) is associated with significant personal, social, and economic costs. However, little is known about specific interpersonal dysfunctions that characterize the PD population. The current study systematically examined these interpersonal dysfunctions. Method The present analyses included 194 patients with PD out of a sample of 201 who were randomized to cognitive-behavioral therapy, panic-focused psychodynamic psychotherapy, or applied relaxation training. Interpersonal dysfunction was measured using the Inventory of Interpersonal Problems–Circumplex (Horowitz, Alden, Wiggins, & Pincus, 2000). Results Individuals with PD reported greater levels of interpersonal distress than that of a normative cohort (especially when PD was accompanied by agoraphobia), but lower than that of a cohort of patients with major depression. There was no single interpersonal profile that characterized PD patients. Symptom-based clusters (with versus without agoraphobia) could not be discriminated on core or central interpersonal problems. Rather, as revealed by cluster analysis based on the pathoplasticity framework, there were two empirically derived interpersonal clusters among PD patients which were not accounted for by symptom severity and were opposite in nature: domineering-intrusive and nonassertive. The empirically derived interpersonal clusters appear to be of clinical utility in predicting alliance development throughout treatment: While the domineering-intrusive cluster did not show any changes in the alliance throughout treatment, the non-assertive cluster showed a process of significant strengthening of the alliance. Conclusions Empirically derived interpersonal clusters in PD provide clinically useful and non-redundant information about individuals with PD. PMID:26030762

Characterizing Literacy and Cognitive Function during Pregnancy and Postpartum.

PubMed

Yee, Lynn M; Kamel, Leslie A; Quader, Zara; Rajan, Priya V; Taylor, Shaneah M; O'Conor, Rachel; Wolf, Michael S; Simon, Melissa A

2017-07-01

Objective  The objective of this study was to characterize health literacy and cognitive function in a diverse cohort of pregnant women. Methods  Pregnant and postpartum women underwent in-depth assessments of health literacy/numeracy and the cognitive domains of verbal ability, working memory, long-term memory, processing speed, and inductive reasoning. Differences by demographic characteristics and gestational age were assessed using chi-square tests and multivariable logistic regression. Results  In this cohort of pregnant ( N  = 77) or postpartum ( N  = 24) women, 41.6% had limited health literacy/numeracy. Women were more likely to score in the lowest quartile for literacy and verbal ability if they were less educated, younger, nonwhite or had Medicaid. These factors were associated with low scores for long-term memory, processing speed, and inductive reasoning. Although there were no differences in literacy or cognitive function by parity or gestational age, postpartum women were more likely to score in the lowest quartile for processing speed (adjusted odds ratio [aOR]: 3.79, 95% confidence interval [CI]: 1.32-10.93) and inductive reasoning (aOR: 4.07, 95% CI: 1.21-13.70). Conclusion  Although postpartum status was associated with reduced inductive reasoning and processing speed, there were no differences in cognitive function across pregnancy. Practice Implications  Postpartum maternal learning may require enhanced support. In addition, cognitive skills and health literacy may be a mediator of perinatal outcomes inequities. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Establishment of intestinal microbiota during early life: a longitudinal, explorative study of a large cohort of Danish infants.

PubMed

Bergström, Anders; Skov, Thomas Hjort; Bahl, Martin Iain; Roager, Henrik Munch; Christensen, Line Brinch; Ejlerskov, Katrine Tschentscher; Mølgaard, Christian; Michaelsen, Kim F; Licht, Tine Rask

2014-05-01

Fecal samples were obtained from a cohort of 330 healthy Danish infants at 9, 18, and 36 months after birth, enabling characterization of interbacterial relationships by use of quantitative PCR targeting 31 selected bacterial 16S rRNA gene targets representing different phylogenetic levels. Nutritional parameters and measures of growth and body composition were determined and investigated in relation to the observed development in microbiota composition. We found that significant changes in the gut microbiota occurred, particularly from age 9 to 18 months, when cessation of breastfeeding and introduction of a complementary feeding induce replacement of a microbiota characterized by lactobacilli, bifidobacteria, and Enterobacteriaceae with a microbiota dominated by Clostridium spp. and Bacteroides spp. Classification of samples by a proxy enterotype based on the relative levels of Bacteroides spp. and Prevotella spp. showed that enterotype establishment occurs between 9 and 36 months. Thirty percent of the individuals shifted enterotype between 18 and 36 months. The composition of the microbiota was most pronouncedly influenced by the time of cessation of breastfeeding. From 9 to 18 months, a positive correlation was observed between the increase in body mass index and the increase of the short-chain-fatty-acid-producing clostridia, the Clostridum leptum group, and Eubacterium hallii. Considering previously established positive associations between rapid infant weight gain, early breastfeeding discontinuation, and later-life obesity, the corresponding microbial findings seen here warrant attention.

Establishment of Intestinal Microbiota during Early Life: a Longitudinal, Explorative Study of a Large Cohort of Danish Infants

PubMed Central

Bergström, Anders; Skov, Thomas Hjort; Bahl, Martin Iain; Roager, Henrik Munch; Christensen, Line Brinch; Ejlerskov, Katrine Tschentscher; Mølgaard, Christian; Michaelsen, Kim F.

2014-01-01

Fecal samples were obtained from a cohort of 330 healthy Danish infants at 9, 18, and 36 months after birth, enabling characterization of interbacterial relationships by use of quantitative PCR targeting 31 selected bacterial 16S rRNA gene targets representing different phylogenetic levels. Nutritional parameters and measures of growth and body composition were determined and investigated in relation to the observed development in microbiota composition. We found that significant changes in the gut microbiota occurred, particularly from age 9 to 18 months, when cessation of breastfeeding and introduction of a complementary feeding induce replacement of a microbiota characterized by lactobacilli, bifidobacteria, and Enterobacteriaceae with a microbiota dominated by Clostridium spp. and Bacteroides spp. Classification of samples by a proxy enterotype based on the relative levels of Bacteroides spp. and Prevotella spp. showed that enterotype establishment occurs between 9 and 36 months. Thirty percent of the individuals shifted enterotype between 18 and 36 months. The composition of the microbiota was most pronouncedly influenced by the time of cessation of breastfeeding. From 9 to 18 months, a positive correlation was observed between the increase in body mass index and the increase of the short-chain-fatty-acid-producing clostridia, the Clostridum leptum group, and Eubacterium hallii. Considering previously established positive associations between rapid infant weight gain, early breastfeeding discontinuation, and later-life obesity, the corresponding microbial findings seen here warrant attention. PMID:24584251

Characterization of suicidal behaviour with self-organizing maps.

PubMed

Leiva-Murillo, José M; López-Castromán, Jorge; Baca-García, Enrique

2013-01-01

The study of the variables involved in suicidal behavior is important from a social, medical, and economical point of view. Given the high number of potential variables of interest, a large population of subjects must be analysed in order to get conclusive results. In this paper, we describe a method based on self-organizing maps (SOMs) for finding the most relevant variables even when their relation to suicidal behavior is strongly nonlinear. We have applied the method to a cohort with more than 8,000 subjects and 600 variables and discovered four groups of variables involved in suicidal behavior. According to the results, there are four main groups of risk factors that characterize the population of suicide attempters: mental disorders, alcoholism, impulsivity, and childhood abuse. The identification of specific subpopulations of suicide attempters is consistent with current medical knowledge and may provide a new avenue of research to improve the management of suicidal cases.

Utility of video-EEG monitoring in a tertiary care epilepsy center.

PubMed

Kumar-Pelayo, M; Oller-Cramsie, M; Mihu, N; Harden, C

2013-09-01

Our video-EEG monitoring (VEEG) unit is part of a typical metropolitan tertiary care center that services a diverse patient population. We aimed to determine if the specific clinical reason for inpatient VEEG was actually resolved. Our method was to retrospectively determine the stated goal of inpatient VEEG and to analyze the outcome of one hundred consecutive adult patients admitted for VEEG. The reason for admission fit into one of four categories: 1) to characterize paroxysmal events as either epileptic or nonepileptic, 2) to localize epileptic foci, 3) to characterize the epilepsy syndrome, and 4) to attempt safe antiepileptic drug adjustment. We found that VEEG was successful in accomplishing the goal of admission in 77% of cases. The remaining 23% failed primarily due to lack of typical events during monitoring. Furthermore, of the overall study cohort, VEEG outcomes altered medical management in 53% and surgery was pursued in 5%. © 2013.

Mucocele-Like Lesions of the Breast: Clinical Outcome and Histological Analysis of 102 Cases

PubMed Central

Meares, Annie L.; Frank, Ryan D.; Degnim, Amy C.; Vierkant, Robert A.; Frost, Marlene H.; Hartmann, Lynn C.; Winham, Stacey J.; Visscher, Daniel W.

2016-01-01

Mucocele-like lesions (MLL) of the breast are characterized by cystic architecture with stromal mucin and frequent atypia, but it is unknown whether they convey long term breast cancer risk. We evaluated 102MLL that were derived from a single institution benign breast disease (BBD) cohort of 13412 women who underwent biopsy from 1967–2001.MLL were histologically characterized by type of lining epithelium, architecture of the lesion, associated atypical hyperplasia (AH) and for incidence of breast cancer (14.8 years median follow-up). A relatively large proportion of MLL (42%) were diagnosed in women >55 years of age AH was significantly more frequent in MML patient compared to the cohort overall (27% vs 5%, p<0.001). Breast cancer has developed in 13 patients with MLL.. This frequency is only slightly higher than population expected rates overall (Standardized incidence ratio (SIR) 2.28, 95% CI 1.21–3.91), and not significantly different from women in the cohort with (non atypical) proliferative breast lesions. Younger women (<45) with MLL had a non-significant increase in risk of cancer compared to the general population (SIR 5.16, 95% CI 1.41–13.23). We conclude MLL is an uncommon breast lesion that is often associated with co-existing AH. However, in women over age 45, MLL do not convey additional risk of breast cancer beyond that associated with the presence of proliferative disease. PMID:26826407

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

PubMed

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

2009-07-08

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

Sclerostin Antibody Treatment Improves the Bone Phenotype of Crtap(-/-) Mice, a Model of Recessive Osteogenesis Imperfecta.

PubMed

Grafe, Ingo; Alexander, Stefanie; Yang, Tao; Lietman, Caressa; Homan, Erica P; Munivez, Elda; Chen, Yuqing; Jiang, Ming Ming; Bertin, Terry; Dawson, Brian; Asuncion, Franklin; Ke, Hua Zhu; Ominsky, Michael S; Lee, Brendan

2016-05-01

Osteogenesis imperfecta (OI) is characterized by low bone mass, poor bone quality, and fractures. Standard treatment for OI patients is limited to bisphosphonates, which only incompletely correct the bone phenotype, and seem to be less effective in adults. Sclerostin-neutralizing antibodies (Scl-Ab) have been shown to be beneficial in animal models of osteoporosis, and dominant OI resulting from mutations in the genes encoding type I collagen. However, Scl-Ab treatment has not been studied in models of recessive OI. Cartilage-associated protein (CRTAP) is involved in posttranslational type I collagen modification, and its loss of function results in recessive OI. In this study, we treated 1-week-old and 6-week-old Crtap(-/-) mice with Scl-Ab for 6 weeks (25 mg/kg, s.c., twice per week), to determine the effects on the bone phenotype in models of "pediatric" and "young adult" recessive OI. Vehicle-treated Crtap(-/-) and wild-type (WT) mice served as controls. Compared with control Crtap(-/-) mice, micro-computed tomography (μCT) analyses showed significant increases in bone volume and improved trabecular microarchitecture in Scl-Ab-treated Crtap(-/-) mice in both age cohorts, in both vertebrae and femurs. Additionally, Scl-Ab improved femoral cortical parameters in both age cohorts. Biomechanical testing showed that Scl-Ab improved parameters of whole-bone strength in Crtap(-/-) mice, with more robust effects in the week 6 to 12 cohort, but did not affect the increased bone brittleness. Additionally, Scl-Ab normalized the increased osteoclast numbers, stimulated bone formation rate (week 6 to 12 cohort only), but did not affect osteocyte density. Overall, our findings suggest that Scl-Ab treatment may be beneficial in the treatment of recessive OI caused by defects in collagen posttranslational modification. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.

Bacterial Composition of the Human Upper Gastrointestinal Tract Microbiome Is Dynamic and Associated with Genomic Instability in a Barrett’s Esophagus Cohort

PubMed Central

Gall, Alevtina; Fero, Jutta; McCoy, Connor; Claywell, Brian C.; Sanchez, Carissa A.; Blount, Patricia L.; Li, Xiaohong; Vaughan, Thomas L.; Matsen, Frederick A.; Reid, Brian J.; Salama, Nina R.

2015-01-01

Background The incidence of esophageal adenocarcinoma (EAC) has increased nearly five-fold over the last four decades in the United States. Barrett’s esophagus, the replacement of the normal squamous epithelial lining with a mucus-secreting columnar epithelium, is the only known precursor to EAC. Like other parts of the gastrointestinal (GI) tract, the esophagus hosts a variety of bacteria and comparisons among published studies suggest bacterial communities in the stomach and esophagus differ. Chronic infection with Helicobacter pylori in the stomach has been inversely associated with development of EAC, but the mechanisms underlying this association remain unclear. Methodology The bacterial composition in the upper GI tract was characterized in a subset of participants (n=12) of the Seattle Barrett’s Esophagus Research cohort using broad-range 16S PCR and pyrosequencing of biopsy and brush samples collected from squamous esophagus, Barrett’s esophagus, stomach corpus and stomach antrum. Three of the individuals were sampled at two separate time points. Prevalence of H. pylori infection and subsequent development of aneuploidy (n=339) and EAC (n=433) was examined in a larger subset of this cohort. Results/Significance Within individuals, bacterial communities of the stomach and esophagus showed overlapping community membership. Despite closer proximity, the stomach antrum and corpus communities were less similar than the antrum and esophageal samples. Re-sampling of study participants revealed similar upper GI community membership in two of three cases. In this Barrett’s esophagus cohort, Streptococcus and Prevotella species dominate the upper GI and the ratio of these two species is associated with waist-to-hip ratio and hiatal hernia length, two known EAC risk factors in Barrett’s esophagus. H. pylori-positive individuals had a significantly decreased incidence of aneuploidy and a non-significant trend toward lower incidence of EAC. PMID:26076489

Air pollution and nonmalignant respiratory mortality in 16 cohorts within the ESCAPE project.

PubMed

Dimakopoulou, Konstantina; Samoli, Evangelia; Beelen, Rob; Stafoggia, Massimo; Andersen, Zorana Jovanovic; Hoffmann, Barbara; Fischer, Paul; Nieuwenhuijsen, Mark; Vineis, Paolo; Xun, Wei; Hoek, Gerard; Raaschou-Nielsen, Ole; Oudin, Anna; Forsberg, Bertil; Modig, Lars; Jousilahti, Pekka; Lanki, Timo; Turunen, Anu; Oftedal, Bente; Nafstad, Per; Schwarze, Per E; Penell, Johanna; Fratiglioni, Laura; Andersson, Niklas; Pedersen, Nancy; Korek, Michal; De Faire, Ulf; Eriksen, Kirsten Thorup; Tjønneland, Anne; Becker, Thomas; Wang, Meng; Bueno-de-Mesquita, Bas; Tsai, Ming-Yi; Eeftens, Marloes; Peeters, Petra H; Meliefste, Kees; Marcon, Alessandro; Krämer, Ursula; Kuhlbusch, Thomas A J; Vossoughi, Mohammad; Key, Timothy; de Hoogh, Kees; Hampel, Regina; Peters, Annette; Heinrich, Joachim; Weinmayr, Gudrun; Concin, Hans; Nagel, Gabriele; Ineichen, Alex; Jacquemin, Bénédicte; Stempfelet, Morgane; Vilier, Alice; Ricceri, Fulvio; Sacerdote, Carlotta; Pedeli, Xanthi; Katsoulis, Michalis; Trichopoulou, Antonia; Brunekreef, Bert; Katsouyanni, Klea

2014-03-15

Prospective cohort studies have shown that chronic exposure to particulate matter and traffic-related air pollution is associated with reduced survival. However, the effects on nonmalignant respiratory mortality are less studied, and the data reported are less consistent. We have investigated the relationship of long-term exposure to air pollution and nonmalignant respiratory mortality in 16 cohorts with individual level data within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE). Data from 16 ongoing cohort studies from Europe were used. The total number of subjects was 307,553. There were 1,559 respiratory deaths during follow-up. Air pollution exposure was estimated by land use regression models at the baseline residential addresses of study participants and traffic-proximity variables were derived from geographical databases following a standardized procedure within the ESCAPE study. Cohort-specific hazard ratios obtained by Cox proportional hazard models from standardized individual cohort analyses were combined using metaanalyses. We found no significant associations between air pollution exposure and nonmalignant respiratory mortality. Most hazard ratios were slightly below unity, with the exception of the traffic-proximity indicators. In this study of 16 cohorts, there was no association between air pollution exposure and nonmalignant respiratory mortality.

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

Echocardiography fails to detect left ventricular noncompaction in a cohort of patients with noncompaction on cardiac magnetic resonance imaging.

PubMed

Diwadkar, Sachin; Nallamshetty, Leelakrishna; Rojas, Carlos; Athienitis, Alexia; Declue, Chris; Cox, Chad; Patel, Aarti; Chae, Sanders H

2017-06-01

Left ventricular noncompaction (LVNC) is a rare disorder characterized by increased left ventricular trabeculation, deep intertrabecular recesses, and a thin compacted myocardial layer with associated clinical sequelae. Cardiac imaging with echocardiogram and cardiac magnetic resonance (CMRI) can detect variable myocardial morphology including excessive trabeculations. Multiple CMRI and echocardiographic criteria have been offered that attempt to identify LVNC morphology. The aim of this study was to assess the utility of echocardiogram in identifying LVNC in a cohort of patients with LVNC detected on CMRI. Echocardiography fails to identify LVNC morphology in a large proportion of patients with LVNC/hypertrabeculation detected on CMRI. There were 1060 CMRI studies collected from 2009 to 2015 at 2 institutions. The patients included in this study (n = 37) met the criteria for LVNC on CMRI and had complete CMRI and echocardiogram images Clinical and imaging data were retrospectively reviewed. Of the 37 patients with LVNC on CMRI, only 10 patients (27%) had LVNC identified on echocardiogram (P < 0.0001, 95% confidence interval: 25.7%-66.2%). Echocardiography and CMRI were also significantly different in terms of identification of distribution of LVNC. Although 21 of 37 patients (57%) had evidence of LVNC in either the anterior or lateral walls on CMRI, there were 0 patients with LVNC detected in the anterior or lateral walls on echocardiogram (P = 0.019). Echocardiogram fails to detect LVNC morphology/hypertrabeculation in a significant number of a cohort of patients with LVNC on CMRI. LVNC may be missed if echocardiogram is the only imaging modality performed in a cardiac evaluation. © 2017 Wiley Periodicals, Inc.

Toxicological and epidemiological studies of cardiovascular effects of ambient air fine particulate matter (PM2.5) and its chemical components: coherence and public health implications.

PubMed

Lippmann, Morton

2014-04-01

Recent investigations on PM2.5 constituents' effects in community residents have substantially enhanced our knowledge on the impacts of specific components, especially the HEI-sponsored National Particle Toxicity Component (NPACT) studies at NYU and UW-LRRI that addressed the impact of long-term PM2.5 exposure on cardiovascular disease (CVD) effects. NYU's mouse inhalation studies at five sites showed substantial variations in aortic plaque progression by geographic region that was coherent with the regional variation in annual IHD mortality in the ACS-II cohort, with both the human and mouse responses being primarily attributable to the coal combustion source category. The UW regressions of associations of CVD events and mortality in the WHI cohort, and of CIMT and CAC progression in the MESA cohort, indicated that [Formula: see text] had stronger associations with CVD-related human responses than OC, EC, or Si. The LRRI's mice had CVD-related biomarker responses to [Formula: see text]. NYU also identified components most closely associated with daily hospital admissions (OC, EC, Cu from traffic and Ni and V from residual oil). For daily mortality, they were from coal combustion ([Formula: see text], Se, and As). While the recent NPACT research on PM2.5 components that affect CVD has clearly filled some major knowledge gaps, and helped to define remaining uncertainties, much more knowledge is needed on the effects in other organ systems if we are to identify and characterize the most effective and efficient means for reducing the still considerable adverse health impacts of ambient air PM. More comprehensive speciation data are needed for better definition of human responses.

Long-term Exposure to Fine Particulate Matter Air Pollution and Mortality Among Canadian Women.

PubMed

Villeneuve, Paul J; Weichenthal, Scott A; Crouse, Daniel; Miller, Anthony B; To, Teresa; Martin, Randall V; van Donkelaar, Aaron; Wall, Claus; Burnett, Richard T

2015-07-01

Long-term exposure to fine particulate matter (PM2.5) has been associated with increased mortality, especially from cardiovascular disease. There are, however, uncertainties about the nature of the exposure-response relation at lower concentrations. In Canada, where ambient air pollution levels are substantially lower than in most other countries, there have been few attempts to study associations between long-term exposure to PM2.5 and mortality. We present a prospective cohort analysis of 89,248 women who enrolled in the Canadian National Breast Screening Study between 1980 and 1985, and for whom residential measures of PM2.5 could be assigned. We derived individual-level estimates of long-term exposure to PM2.5 from satellite observations. We linked cohort records to national mortality data to ascertain mortality between 1980 and 2005. We used Cox proportional hazards models to characterize associations between PM2.5 and several causes of death. The hazard ratios (HRs) and 95% confidence intervals (CIs) computed from these models were adjusted for several individual and neighborhood-level characteristics. The cohort was composed predominantly of Canadian-born (82%) and married (80%) women. The median residential concentration of PM2.5 was 9.1 μg/m(3) (standard deviation = 3.4). In fully adjusted models, a 10 μg/m(3) increase in PM2.5 exposure was associated with elevated risks of nonaccidental (HR: 1.12; 95% CI = 1.04, 1.19), and ischemic heart disease mortality (HR: 1.34; 95% CI = 1.09, 1.66). The findings from this study provide additional support for the hypothesis that exposure to very low levels of ambient PM2.5 increases the risk of cardiovascular mortality.

Effectiveness of direct-acting antiviral therapy for hepatitis C in difficult-to-treat patients in a safety-net health system: a retrospective cohort study.

PubMed

Yek, Christina; de la Flor, Carolina; Marshall, John; Zoellner, Cindy; Thompson, Grace; Quirk, Lisa; Mayorga, Christian; Turner, Barbara J; Singal, Amit G; Jain, Mamta K

2017-11-20

Direct-acting antivirals (DAAs) have revolutionized chronic hepatitis C (HCV) treatment, but real-world effectiveness among vulnerable populations, including uninsured patients, is lacking. This study was conducted to characterize the effectiveness of DAAs in a socioeconomically disadvantaged and underinsured patient cohort. This retrospective observational study included all patients undergoing HCV treatment with DAA-based therapy between April 2014 and June 2016 at a large urban safety-net health system (Parkland Health and Hospital System, Dallas, TX, USA). The primary outcome was sustained virologic response (SVR), with secondary outcomes including treatment discontinuation, treatment relapse, and loss to follow-up. DAA-based therapy was initiated in 512 patients. The cohort was socioeconomically disadvantaged (56% uninsured and 13% Medicaid), with high historic rates of alcohol (41%) and substance (50%) use, and mental health disorders (38%). SVR was achieved in 90% of patients (n = 459); 26 patients (5%) were lost to follow-up. SVR was significantly lower in patients with decompensated cirrhosis (82% SVR; OR 0.37, 95% CI 0.16-0.85) but did not differ by insurance status (P = 0.98) or alcohol/substance use (P = 0.34). Reasons for treatment failure included loss to follow-up (n = 26, 5%), viral relapse (n = 16, 3%), non-treatment-related death (n = 7, 1%), and treatment discontinuation (n = 4, 1%). Of patients with viral relapse, 6 reported non-compliance and have not been retreated, 5 have been retreated and achieved SVR, 4 have undergone resistance testing but not yet initiated retreatment, and 1 was lost to follow-up. Effective outcomes with DAA-based therapy can be achieved in difficult-to-treat underinsured populations followed in resource-constrained safety-net health systems.

Evaluation of a clinical risk index for advanced colorectal neoplasia among a North American population of screening age.

PubMed

Ruco, Arlinda; Stock, David; Hilsden, Robert J; McGregor, S Elizabeth; Paszat, Lawrence F; Saskin, Refik; Rabeneck, Linda

2015-11-19

A clinical risk index employing age, sex, family history of colorectal cancer (CRC), smoking history and body mass index (BMI) may be useful for prioritizing screening with colonoscopy. The aim of this study was to conduct an external evaluation of a previously published risk index for advanced neoplasia (AN) in a large, well-characterized cohort. Five thousand one hundred thirty-seven asymptomatic persons aged 50 to 74 (54.9 % women) with a mean age (SD) of 58.3 (6.2) years were recruited for the study from a teaching hospital and colorectal cancer screening centre between 2003 and 2011. All participants underwent a complete screening colonoscopy and removal of all polyps. AN was defined as cancer or a tubular adenoma, traditional serrated adenoma (TSA), or sessile serrated adenoma (SSA) with villous characteristics (≥25% villous component), and/or high-grade dysplasia and/or diameter ≥10 mm. Risk scores for each participant were summed to derive an overall score (0-8). The c-statistic was used to measure discriminating ability of the risk index. The prevalence of AN in the study cohort was 6.8 %. The likelihood of detecting AN increased from 3.6 to 13.1 % for those with a risk score of 1 to 6 respectively. The c-statistic for the multivariable logistic model in our cohort was 0.64 (95 % CI = 0.61-067) indicating modest overlap between risk scores. The risk index for AN using age, sex, family history, smoking history and BMI was found to be of limited discriminating ability upon external validation. The index requires further refinement to better predict AN in average risk persons of screening age.

Eczema Is Associated with Childhood Speech Disorder: A Retrospective Analysis from the National Survey of Children’s Health and the National Health Interview Survey

PubMed Central

Strom, Mark A.; Silverberg, Jonathan I.

2016-01-01

Objective To determine if eczema is associated with an increased risk of a speech disorder. Study design We analyzed data on 354 416 children and adolescents from 19 US population-based cohorts: the 2003–2004 and 2007–2008 National Survey of Children’s Health and 1997–2013 National Health Interview Survey, each prospective, questionnaire-based cohorts. Results In multivariate survey logistic regression models adjusting for sociodemographics and comorbid allergic disease, eczema was significantly associated with higher odds of speech disorder in 12 of 19 cohorts (P < .05). The pooled prevalence of speech disorder in children with eczema was 4.7% (95% CI 4.5%–5.0%) compared with 2.2% (95% CI 2.2%–2.3%) in children without eczema. In pooled multivariate analysis, eczema was associated with increased odds of speech disorder (aOR [95% CI] 1.81 [1.57–2.05], P < .001). In a single study assessing eczema severity, mild (1.36 [1.02–1.81], P = .03) and severe eczema (3.56 [1.70–7.48], P < .001) were associated with higher odds of speech disorder. History of eczema was associated with moderate (2.35 [1.34–4.10], P = .003) and severe (2.28 [1.11–4.72], P = .03) speech disorder. Finally, significant interactions were found, such that children with both eczema and attention deficit disorder with or without hyperactivity or sleep disturbance had vastly increased risk of speech disorders than either by itself. Conclusions Pediatric eczema may be associated with increased risk of speech disorder. Further, prospective studies are needed to characterize the exact nature of this association. PMID:26520915

Interleukin-1β gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study.

PubMed

Kertai, Miklos D; Ji, Yunqi; Li, Yi-Ju; Mathew, Joseph P; Daubert, James P; Podgoreanu, Mihai V

2016-04-01

We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors. All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as > 440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes -involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes- was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats. After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1β (IL1β), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024). The results suggest a contribution of IL1β in modulating susceptibility to postoperative QTc prolongation after cardiac surgery.

Leukemia, lymphoma and multiple myeloma mortality (1950-1999) and incidence (1969-1999) in the Eldorado uranium workers cohort.

PubMed

Zablotska, Lydia B; Lane, Rachel S D; Frost, Stanley E; Thompson, Patsy A

2014-04-01

Uranium workers are chronically exposed to low levels of radon decay products (RDP) and gamma (γ) radiation. Risks of leukemia from acute and high doses of γ-radiation are well-characterized, but risks from lower doses and dose-rates and from RDP exposures are controversial. Few studies have evaluated risks of other hematologic cancers in uranium workers. The purpose of this study was to analyze radiation-related risks of hematologic cancers in the cohort of Eldorado uranium miners and processors first employed in 1932-1980 in relation to cumulative RDP exposures and γ-ray doses. The average cumulative RDP exposure was 100.2 working level months and the average cumulative whole-body γ-radiation dose was 52.2 millisievert. We identified 101 deaths and 160 cases of hematologic cancers in the cohort. Overall, male workers had lower mortality and cancer incidence rates for all outcomes compared with the general Canadian male population, a likely healthy worker effect. No statistically significant association between RDP exposure or γ-ray doses, or a combination of both, and mortality or incidence of any hematologic cancer was found. We observed consistent but non-statistically significant increases in risks of chronic lymphocytic leukemia (CLL) and Hodgkin lymphoma (HL) incidence and non-Hodgkin lymphoma (NHL) mortality with increasing γ-ray doses. These findings are consistent with recent studies of increased risks of CLL and NHL incidence after γ-radiation exposure. Further research is necessary to understand risks of other hematologic cancers from low-dose exposures to γ-radiation. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

TPMT Genetic Variations in Populations of the Russian Federation

PubMed Central

Samochatova, Elena V; Chupova, Natalia V; Rudneva, Anastassia; Makarova, Olga; Nasedkina, Tatyana V; Fedorova, Olga E; Glotov, Andrei S; Kozhekbaeva, Zh.; Maiorova, Olga A; Roumyantsev, Alexander G; Krynetski, Eugene Y; Krynetskaia, Natalia F; Evans, William E; Ribeiro, Raul C

2009-01-01

Background Polymorphisms that reduce the activity of thiopurine S-methyltransferase (TPMT) cause adverse reactions to conventional doses of thiopurines, routinely used for antileukemic and immunosuppressive treatment. There are more than 20 variant alleles of TPMT that cause decreased enzymatic activity. We studied the most common variant alleles of TPMT and their frequency distribution in a large cohort of multiracial residents in the Russian Federation and compared their frequencies in children with and without malignancy to determine whether TPMT gene abnormality is associated with hematologic malignancy. Procedure The TPMT biochip was used to detect 6 TPMT single nucleotide polymorphisms (SNPs) corresponding to 7 TPMT-deficiency alleles (TPMT*2, TPMT*3A, TPMT*3B, TPMT*3C, TPMT*3D, TPMT*7, and TPMT*8). We analyzed allele frequencies in the whole cohort, the childhood cancer group, and the non-cancer group. We also characterized disease features and outcome according to the presence of TPMT SNPs in children with acute lymphoblastic leukemia (ALL). Results Fifty-five (5.5%) study participants overall had heterozygous TPMT genotypes (1 variant and 1 wild-type allele): TPMT*1/*3A (n=45; 4.5%), TPMT*1/*3C (n=8; 0.8%), and TPMT*1/*2 (n=2; 0.2%). TPMT SNPs were more frequent in children with hematologic malignancy than in other participants (7.5% vs. 4.0%, P = 0.02). We found no significant association between TPMT SNPs and ALL treatment outcome (median follow-up, 31.3 months). Conclusions TPMT*3A is the most prevalent variant allele in the Russian Federation. The estimated frequency of variant alleles in the study cohort (5.5%) was similar to that observed in the White populations in the U.S. and Eastern Europe. PMID:19034904

Longer duration of homelessness is associated with a lower likelihood of non-detectable plasma HIV-1 RNA viral load among people who use illicit drugs in a Canadian setting.

PubMed

Loh, Jane; Kennedy, Mary Clare; Wood, Evan; Kerr, Thomas; Marshall, Brandon; Parashar, Surita; Montaner, Julio; Milloy, M-J

2016-11-01

Homelessness is common among people who use drugs (PWUD) and, for those living with HIV/AIDS, an important contributor to sub-optimal HIV treatment outcomes. This study aims to investigate the relationship between the duration of homelessness and the likelihood of plasma HIV-1 RNA viral load (VL) non-detectability among a cohort of HIV-positive PWUD. We used data from the ACCESS study, a long-running prospective cohort study of HIV-positive PWUD linked to comprehensive HIV clinical records including systematic plasma HIV-1 RNA VL monitoring. We estimated the longitudinal relationship between the duration of homelessness and the likelihood of exhibiting a non-detectable VL (i.e., <500 copies/mL plasma) using generalized linear mixed-effects modelling. Between May 1996 and June 2014, 922 highly active antiretroviral therapy-exposed participants were recruited and contributed 8188 observations. Of these, 4800 (59%) were characterized by non-detectable VL. Participants reported they were homeless in 910 (11%) interviews (median: six months, interquartile range: 6-12 months). A longer duration of homelessness was associated with lower odds of VL non-detectability (adjusted odds ratio = 0.71 per six-month period of homelessness, 95% confidence interval: 0.60-0.83) after adjustment for age, ancestry, drug use patterns, engagement in addiction treatment, and other potential confounders. Longer durations of episodes of homelessness in this cohort of HIV-positive illicit drug users were associated with a lower likelihood of plasma VL non-detectability. Our findings suggest that interventions that seek to promptly house homeless individuals, such as Housing First approaches, might assist in maximizing the clinical and public health benefits of antiretroviral therapy among people living with HIV/AIDS.

Effect of beta-blockers on exacerbation rate and lung function in chronic obstructive pulmonary disease (COPD).

PubMed

Duffy, Sean; Marron, Robert; Voelker, Helen; Albert, Richard; Connett, John; Bailey, William; Casaburi, Richard; Cooper, J Allen; Curtis, Jeffrey L; Dransfield, Mark; Han, MeiLan K; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando; Lazarus, Stephen; Niewoehner, Dennis; Scanlon, Paul D; Sciurba, Frank; Scharf, Steven; Reed, Robert M; Washko, George; Woodruff, Prescott; McEvoy, Charlene; Aaron, Shawn; Sin, Don; Criner, Gerard J

2017-06-19

Beta-blockers are commonly prescribed for patients with cardiovascular disease. Providers have been wary of treating chronic obstructive pulmonary disease (COPD) patients with beta-blockers due to concern for bronchospasm, but retrospective studies have shown that cardio-selective beta-blockers are safe in COPD and possibly beneficial. However, these benefits may reflect symptom improvements due to the cardiac effects of the medication. The purpose of this study is to evaluate associations between beta-blocker use and both exacerbation rates and longitudinal measures of lung function in two well-characterized COPD cohorts. We retrospectively analyzed 1219 participants with over 180 days of follow up from the STATCOPE trial, which excluded most cardiac comorbidities, and from the placebo arm of the MACRO trial. Primary endpoints were exacerbation rates per person-year and change in spirometry over time in association with beta blocker use. Overall 13.9% (170/1219) of participants reported taking beta-blockers at enrollment. We found no statistically significant differences in exacerbation rates with respect to beta-blocker use regardless of the prevalence of cardiac comorbidities. In the MACRO cohort, patients taking beta-blockers had an exacerbation rate of 1.72/person-year versus a rate of 1.71/person-year in patients not taking beta-blockers. In the STATCOPE cohort, patients taking beta-blockers had an exacerbation rate of 1.14/person-year. Patients without beta-blockers had an exacerbation rate of 1.34/person-year. We found no detrimental effect of beta blockers with respect to change in lung function over time. We found no evidence that beta-blocker use was unsafe or associated with worse pulmonary outcomes in study participants with moderate to severe COPD.

Adequacy of Mental Health Services for HIV-Positive Patients with Depression: Ontario HIV Treatment Network Cohort Study

PubMed Central

Choi, Stephanie K. Y.; Boyle, Eleanor; Cairney, John; Gardner, Sandra; Collins, Evan J.; Bacon, Jean; Rourke, Sean B.

2016-01-01

Background Major depression can profoundly impact clinical and quality-of-life outcomes of people living with HIV, and this disease is underdiagnosed and undertreated in many HIV-positive individuals. Here, we describe the prevalence of publicly funded primary and secondary mental health service use and antidepressant use, as well as mental health care for depression in accordance with existing Canadian guidelines for HIV-positive patients with depression in Ontario, Canada. Methods We conducted a prospective cohort study linking data from the Ontario HIV Treatment Network Cohort Study with administrative health databases in the province of Ontario, Canada. Current depression was assessed using the Center for Epidemiologic Depression Scale or the Kessler Psychological Distress Scale. Multivariable regressions were used to characterize prevalence outcomes. Results Of 990 HIV-positive patients with depression, 493 (50%) patients used mental health services; 182 (18%) used primary services (general practitioners); 176 (18%) used secondary services (psychiatrists); and 135 (14%) used both. Antidepressants were used by 407 (39%) patients. Patients who identified as gay, lesbian, or bisexual, as having low income or educational attainment, or as non-native English speakers or immigrants to Canada were less likely to obtain care. Of 493 patients using mental health services, 250 (51%) received mental health care for depression in accordance with existing Canadian guidelines. Conclusions Our results showed gaps in delivering publicly funded mental health services to depressed HIV-positive patients and identified unequal access to these services, particularly among vulnerable groups. More effective mental health policies and better access to mental health services are required to address HIV-positive patient needs and reduce depression’s impact on their lives. PMID:27280751

Long-term follow-up and outcome in patients with recurrent respiratory laryngeal papillomatosis.

PubMed

Rasmussen, Eva Rye; Schnack, Didde T; Jørkov, Andreas Schjellerup; Raja, Anna Axelsson; Olsen, Caroline Holkmann; Homøe, Preben

2017-12-01

Recurrent respiratory papillomatosis is characterized by wart-like lesions of the upper airway and is most frequently caused by human papillomavirus (HPV). The disease has significant impact on quality of life due to potential airway obstruction, dysphonia and the need for serial surgeries. The main objective of this study was to describe patient characteristics and long-term follow-up data in a Danish cohort with the disease. The study was a longitudinal retrospective cohort-study using data from electronic medical records and a pathology database. A total of 61 adult and four juvenile patients were identified. The male-to-female ratio was 2.4. In the adult population, the mean age at onset was 45 years. The median number of surgeries was four (interquartile range: 2.8). The mean follow-up time was 8.7 years (range: 7 days-30 years). Three cases of malignant transformation were observed. In the juvenile population, the mean age of onset was 8.5 years (range: 3-12 years). The mean follow-up time was 11.5 years (range: 2-23 years), and the number of surgeries per year at risk was one/year. CO2-laser and microdebrider were the surgical techniques usually employed. 43% of histopathologic analyses could detect HPV infection (subtype 6 or 11). More males than females suffer from respiratory papillomatosis; age of onset was either in childhood or in mid-life. Use of CO2-laser or microdebrider was the preferred surgical approach in this cohort. none. not relevant. Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Microbiome Heterogeneity Characterizing Intestinal Tissue and Inflammatory Bowel Disease Phenotype.

PubMed

Tyler, Andrea D; Kirsch, Richard; Milgrom, Raquel; Stempak, Joanne M; Kabakchiev, Boyko; Silverberg, Mark S

2016-04-01

Inflammatory bowel disease has been associated with differential abundance of numerous organisms when compared to healthy controls (HCs); however, few studies have investigated variability in the microbiome across intestinal locations and how this variability might be related to disease location and phenotype. In this study, we have analyzed the microbiome of a large cohort of individuals recruited at Mount Sinai Hospital in Toronto, Canada. Biopsies were taken from subjects with Crohn's disease, ulcerative colitis, and HC, and also individuals having undergone ileal pouch-anal anastomosis for treatment of ulcerative colitis or familial adenomatous polyposis. Microbial 16S rRNA was sequenced using the Illumina MiSeq platform. We observed a great deal of variability in the microbiome characterizing different sampling locations. Samples from pouch and afferent limb were comparable in microbial composition. When comparing sigmoid and terminal ileum samples, more differences were observed. The greatest number of differentially abundant microbes was observed when comparing either pouch or afferent limb samples to sigmoid or terminal ileum. Despite these differences, we were able to observe modest microbial variability between inflammatory bowel disease phenotypes and HCs, even when controlling for sampling location and additional experimental factors. Most detected associations were observed between HCs and Crohn's disease, with decreases in specific genera in the families Ruminococcaceae and Lachnospiraceae characterizing tissue samples from individuals with Crohn's disease. This study highlights important considerations when analyzing the composition of the microbiome and also provides useful insight into differences in the microbiome characterizing these seemingly related phenotypes.

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.

Simple maneuvers to reduce the incidence of false-negative findings for contralateral patent processus vaginalis during laparoscopic hernia repair in children: a comparative study between 2 cohorts.

PubMed

Tam, Yuk Him; Wong, Yuen Shan; Chan, Kin Wai; Pang, Kristine Kit Yi; Tsui, Siu Yan; Mou, Jennifer Wai Cheung; Sihoe, Jennifer Dart Yin; Lee, Kim Hung

2013-04-01

Transumbilical or transinguinal laparoscopic evaluation for contralateral patent processus vaginalis (CPPV) is commonly performed during laparoscopic or open hernia repair in children but may occasionally give false-negative findings. A retrospective study was conducted to compare 2 cohorts of children who underwent laparoscopic repair for clinically demonstrated unilateral inguinal hernia and evaluation for CPPV by transumbilical laparoscopy during the study periods of 2004 to 2007 (cohort 1) and 2008 to 2011 (cohort 2). Cohort 1 was a known historical cohort with CPPV being evaluated by laparoscopic inspection alone, whereas additional maneuvers were adopted in cohort 2. There were 395 and 564 patients in cohorts 1 and 2, respectively. There was no difference between the 2 cohorts in age of patients, sex distribution, laterality of clinically demonstrated inguinal hernia, and follow-up period at the time of data collection. More CPPV were diagnosed in cohort 2 than cohort 1(36.2% vs 25.8%; P < .01). 4 children (1.4%) developed metachronous inguinal hernia following negative laparoscopic evaluation for CPPV in cohort 1 compared with none from cohort 2 at a similar median follow-up period (P < .05). The additional maneuvers appear to be superior to laparoscopic inspection alone to evaluate CPPV during laparoscopic hernia repair in children. Copyright © 2013 Elsevier Inc. All rights reserved.

Prevalence and Severity of Voice and Swallowing Difficulties in Mitochondrial Disease

ERIC Educational Resources Information Center

Read, Jennifer L.; Whittaker, Roger G.; Miller, Nick; Clark, Sue; Taylor, Robert; McFarland, Robert; Turnbull, Douglass

2012-01-01

Background: Mutations of mitochondrial DNA (mtDNA) cause a broad spectrum of clinical phenotypes. Anecdotal evidence suggests that voice and swallow problems are a common feature of these diseases. Aims: To characterize accurately the prevalence and severity of voice and swallow problems in a large cohort of patients with mitochondrial disease.…

Functional characterization of IgA-targeted bacterial taxa from undernourished Malawian children that produce diet-dependent enteropathy

USDA-ARS?s Scientific Manuscript database

To gain insights into the interrelationships among childhood undernutrition, the gut microbiota, and gut mucosal immune/barrier function, we purified bacterial strains targeted by immunoglobulin A (IgA) from the fecal microbiota of two cohorts of Malawian infants and children. IgA responses to sever...

Depressive symptoms in the Belgian population: disentangling age and cohort effects.

PubMed

Brault, Marie-Christine; Meuleman, Bart; Bracke, Piet

2012-06-01

Although the association between age and depression has been previously demonstrated, uncertainty remains because of the confounding relationship existing between age and cohort. A study by Yang (J Health Soc Behav 48(1):16, 2007) has evidenced important cohort effects and age-by-cohort interactions in depressive symptoms among US citizens. A crucial limitation, however, is that this study confines itself to elderly population. The objective of the present study is to bring further clarification to the association between age, cohort membership and depressive symptoms, by analyzing a sample with a wider age range. The Panel Study of Belgian Households is a prospective longitudinal survey, following adults ages 25-74, annually from 1992 to 2002. Missing data were replaced using multiple imputation, allowing for a complete dataset (N = 7,000) at each wave. Respondents were classified into one of five birth cohorts: 1918-1927; 1928-1937; 1938-1947; 1948-1957; 1958-1967. Frequency of depressive symptoms was reported using a modified version of the Health and Daily Living form. Growth curve modeling was used to determine the effect of age and cohort on depression trajectory. All cohorts differed significantly from one another, with recent cohorts always obtaining the highest mean HDL-depression score. The intensity of depressive symptoms increases linearly with age, but significant age-by-cohorts interactions were detected, indicating that the relationship between age and depression varies across cohorts. No evidence of a WW2 effect was found. The association between age and depression has to take cohort membership into account. Cohort replacement effects explain the increase in depression in Belgium.

Bipolar mood state reflected in cortico-amygdala resting state connectivity: A cohort and longitudinal study.

PubMed

Brady, Roscoe O; Margolis, Allison; Masters, Grace A; Keshavan, Matcheri; Öngür, Dost

2017-08-01

Using resting-state functional magnetic resonance imaging (rsfMRI), we previously compared cohorts of bipolar I subjects in a manic state to those in a euthymic state to identify mood state-specific patterns of cortico-amygdala connectivity. Our results suggested that mania is reflected in the disruption of emotion regulation circuits. We sought to replicate this finding in a group of subjects with bipolar disorder imaged longitudinally across states of mania and euthymia METHODS: We divided our subjects into three groups: 26 subjects imaged in a manic state, 21 subjects imaged in a euthymic state, and 10 subjects imaged longitudinally across both mood states. We measured differences in amygdala connectivity between the mania and euthymia cohorts. We then used these regions of altered connectivity to examine connectivity in the longitudinal bipolar group using a within-subjects design. Our findings in the mania vs euthymia cohort comparison were replicated in the longitudinal analysis. Bipolar mania was differentiated from euthymia by decreased connectivity between the amygdala and pre-genual anterior cingulate cortex. Mania was also characterized by increased connectivity between amygdala and the supplemental motor area, a region normally anti-correlated to the amygdala in emotion regulation tasks. Stringent controls for movement effects limited the number of subjects in the longitudinal sample. In this first report of rsfMRI conducted longitudinally across mood states, we find that previously observed between-group differences in amygdala connectivity are also found longitudinally within subjects. These results suggest resting state cortico-amygdala connectivity is a biomarker of mood state in bipolar disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

Upper-Extremity Deep-Vein Thrombosis: A Retrospective Cohort Evaluation of Thrombotic Risk Factors at a University Teaching Hospital Antithrombosis Clinic.

PubMed

Stone, Rebecca H; Bress, Adam P; Nutescu, Edith A; Shapiro, Nancy L

2016-08-01

Upper-extremity deep-vein thrombosis (UEDVT) causes significant morbidity and mortality and is not well characterized in the existing literature, particularly in underrepresented minorities such as African Americans. To describe the characteristics of a cohort of patients with UEDVT seen at an urban academic medical center. This was a retrospective cohort study among patients with a confirmed UEDVT at the University of Illinois Hospital and Health Sciences System between 1996 and 2011. Patients were identified by ICD-9 code for UEDVT. Variables collected include thrombotic risk factors and outcomes, including recurrent thrombosis and bleeding. We identified 229 patients with UEDVT; 71% were African American, and 11% were diagnosed with sickle cell disease. The average number of UEDVT risk factors was 4.40 ± 1.5, the most common being central venous catheter (CVC) use (178, 78%). In the year following UEDVT, 13% experienced recurrent thrombosis, and 6% experienced major bleeding. Of 181 patients receiving warfarin after an UEDVT, 36% of international normalized ratio (INR) values were therapeutic. Patients with sickle cell disease had a lower proportion of INRs within the target range (25% vs 38%, P < 0.01), and were more likely to be lost to follow-up (67% vs 46%, P = 0.05) and experience a recurrent thrombotic event (29% vs 11%, P = 0.02). A CVC is the most common risk factor for UEDVT; however, patients with sickle cell disease demonstrate additional unique demographics and risk factors. Patients included in this underrepresented demographic cohort had a low quality of anticoagulation control, particularly those with sickle cell disease. © The Author(s) 2016.

Development and validation of a surgical-pathologic staging and scoring system for cervical cancer

PubMed Central

Zhou, Hang; Tang, Fangxu; Jia, Yao; Hu, Ting; Sun, Haiying; Yang, Ru; Chen, Yile; Cheng, Xiaodong; Lv, Weiguo; Wu, Li; Zhou, Jin; Wang, Shaoshuai; Huang, Kecheng; Wang, Lin; Yao, Yuan; Yang, Qifeng; Yang, Xingsheng; Zhang, Qinghua; Han, Xiaobing; Lin, Zhongqiu; Xing, Hui; Qu, Pengpeng; Cai, Hongbing; Song, Xiaojie; Tian, Xiaoyu; Shen, Jian; Xi, Ling; Li, Kezhen; Deng, Dongrui; Wang, Hui; Wang, Changyu; Wu, Mingfu; Zhu, Tao; Chen, Gang; Gao, Qinglei; Wang, Shixuan; Hu, Junbo; Kong, Beihua; Xie, Xing; Ma, Ding

2016-01-01

Background Most cervical cancer patients worldwide receive surgical treatments, and yet the current International Federation of Gynecology and Obstetrics (FIGO) staging system do not consider surgical-pathologic data. We propose a more comprehensive and prognostically valuable surgical-pathologic staging and scoring system (SPSs). Methods Records from 4,220 eligible cervical cancer cases (Cohort 1) were screened for surgical-pathologic risk factors. We constructed a surgical-pathologic staging and SPSs, which was subsequently validated in a prospective study of 1,104 cervical cancer patients (Cohort 2). Results In Cohort 1, seven independent risk factors were associated with patient outcome: lymph node metastasis (LNM), parametrial involvement, histological type, grade, tumor size, stromal invasion, and lymph-vascular space invasion (LVSI). The FIGO staging system was revised and expanded into a surgical-pathologic staging system by including additional criteria of LNM, stromal invasion, and LVSI. LNM was subdivided into three categories based on number and location of metastases. Inclusion of all seven prognostic risk factors improves practical applicability. Patients were stratified into three SPSs risk categories: zero-, low-, and high-score with scores of 0, 1 to 3, and ≥4 (P=1.08E-45; P=6.15E-55). In Cohort 2, 5-year overall survival (OS) and disease-free survival (DFS) outcomes decreased with increased SPSs scores (P=9.04E-15; P=3.23E-16), validating the approach. Surgical-pathologic staging and SPSs show greater homogeneity and discriminatory utility than FIGO staging. Conclusions Surgical-pathologic staging and SPSs improve characterization of tumor severity and disease invasion, which may more accurately predict outcome and guide postoperative therapy. PMID:27014971

Primary central nervous system lymphoma and glioblastoma differentiation based on conventional magnetic resonance imaging by high-throughput SIFT features.

PubMed

Chen, Yinsheng; Li, Zeju; Wu, Guoqing; Yu, Jinhua; Wang, Yuanyuan; Lv, Xiaofei; Ju, Xue; Chen, Zhongping

2018-07-01

Due to the totally different therapeutic regimens needed for primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM), accurate differentiation of the two diseases by noninvasive imaging techniques is important for clinical decision-making. Thirty cases of PCNSL and 66 cases of GBM with conventional T1-contrast magnetic resonance imaging (MRI) were analyzed in this study. Convolutional neural networks was used to segment tumor automatically. A modified scale invariant feature transform (SIFT) method was utilized to extract three-dimensional local voxel arrangement information from segmented tumors. Fisher vector was proposed to normalize the dimension of SIFT features. An improved genetic algorithm (GA) was used to extract SIFT features with PCNSL and GBM discrimination ability. The data-set was divided into a cross-validation cohort and an independent validation cohort by the ratio of 2:1. Support vector machine with the leave-one-out cross-validation based on 20 cases of PCNSL and 44 cases of GBM was employed to build and validate the differentiation model. Among 16,384 high-throughput features, 1356 features show significant differences between PCNSL and GBM with p < 0.05 and 420 features with p < 0.001. A total of 496 features were finally chosen by improved GA algorithm. The proposed method produces PCNSL vs. GBM differentiation with an area under the curve (AUC) curve of 99.1% (98.2%), accuracy 95.3% (90.6%), sensitivity 85.0% (80.0%) and specificity 100% (95.5%) on the cross-validation cohort (and independent validation cohort). Since the local voxel arrangement characterization provided by SIFT features, proposed method produced more competitive PCNSL and GBM differentiation performance by using conventional MRI than methods based on advanced MRI.

Characterization of ischemic index using ultra-widefield fluorescein angiography in patients with focal and diffuse recalcitrant diabetic macular edema.

PubMed

Patel, Ravi D; Messner, Leonard V; Teitelbaum, Bruce; Michel, Kimberly A; Hariprasad, Seenu M

2013-06-01

To explore the association of angiographic nonperfusion in focal and diffuse recalcitrant diabetic macular edema (DME) in diabetic retinopathy (DR). A retrospective, observational case series of patients with the diagnosis of recalcitrant DME for at least 2 years placed into 1 of 4 cohorts based on the degree of DR. A total of 148 eyes of 76 patients met the inclusion criteria at 1 academic institution. Ultra-widefield fluorescein angiography (FA) images and spectral-domain optical coherence tomography (SD OCT) images were obtained on all patients. Ultra-widefield FA images were graded for quantity of nonperfusion, which was used to calculate ischemic index. Main outcome measures were mean ischemic index, mean change in central macular thickness (CMT), and mean number of macular photocoagulation treatments over the 2-year study period. The mean ischemic index was 47% (SD 25%; range 0%-99%). The mean ischemic index of eyes within Cohorts 1, 2, 3, and 4 was 0%, 34% (range 16%-51%), 53% (range 32%-89%), and 65% (range 47%-99%), respectively. The mean percentage decrease in CMT in Cohorts 1, 2, 3, and 4 were 25.2%, 19.1%, 11.6%, and 7.2%, respectively. The mean number of macular photocoagulation treatments in Cohorts 1, 2, 3, and 4 was 2.3, 4.8, 5.3, and 5.7, respectively. Eyes with larger areas of retinal nonperfusion and greater severity of DR were found to have the most recalcitrant DME, as evidenced by a greater number of macular photocoagulation treatments and less reduction in SD OCT CMT compared with eyes without retinal nonperfusion. Areas of untreated retinal nonperfusion may generate biochemical mediators that promote ischemia and recalcitrant DME. Copyright © 2013 Elsevier Inc. All rights reserved.

Patient-level clinically meaningful improvements in activities of daily living and pain after total hip arthroplasty: data from a large US institutional registry.

PubMed

Singh, Jasvinder A; Lewallen, David G

2013-06-01

To characterize patient-level clinically meaningful improvements in pain and limitation of key activities of daily living (ADLs) after primary or revision total hip arthroplasty (THA). We analysed prospectively collected data from the Mayo Clinic Total Joint Registry to study clinically meaningful improvements in index hip pain severity and limitation in seven key ADLs (walking, climbing stairs, putting on shoes/socks, picking up objects, getting in/out of car, rising from a chair and sitting), from preoperative to 2- and 5-year post-THA. The primary THA cohort consisted of 6168 responders preoperatively, 5707 at 2 years and 3289 at 5 years postoperatively. The revision THA cohort consisted of 2063 responders preoperatively, 2682 at 2 years and 1627 at 5 years postoperatively. In the primary THA cohort, clinically meaningful pain reduction to mild or no hip pain at 2 years was reported by 94% with moderate and 91% with severe preoperative pain; respective proportions were 91% and 89% at 5-year follow-up. For revision THA, respective proportions were 84% and 77% at 2 years and 80% and 78% at 5 years. In the primary THA cohort, up to 4% with moderate and 17% with severe preoperative ADL limitation reported severe limitation in the respective activity 2 years post-primary THA; at 5 years, the respective proportions were up to 7% and 20%. Respective proportions for revision THA were up to 10% and 26% at 2 years and 13% and 30% at 5 years. These comprehensive data for patient-level clinically meaningful improvements in pain and seven key ADLs can help patients set realistic goals for improvement after THA.

An administrative claims model for profiling hospital 30-day mortality rates for pneumonia patients.

PubMed

Bratzler, Dale W; Normand, Sharon-Lise T; Wang, Yun; O'Donnell, Walter J; Metersky, Mark; Han, Lein F; Rapp, Michael T; Krumholz, Harlan M

2011-04-12

Outcome measures for patients hospitalized with pneumonia may complement process measures in characterizing quality of care. We sought to develop and validate a hierarchical regression model using Medicare claims data that produces hospital-level, risk-standardized 30-day mortality rates useful for public reporting for patients hospitalized with pneumonia. Retrospective study of fee-for-service Medicare beneficiaries age 66 years and older with a principal discharge diagnosis of pneumonia. Candidate risk-adjustment variables included patient demographics, administrative diagnosis codes from the index hospitalization, and all inpatient and outpatient encounters from the year before admission. The model derivation cohort included 224,608 pneumonia cases admitted to 4,664 hospitals in 2000, and validation cohorts included cases from each of years 1998-2003. We compared model-derived state-level standardized mortality estimates with medical record-derived state-level standardized mortality estimates using data from the Medicare National Pneumonia Project on 50,858 patients hospitalized from 1998-2001. The final model included 31 variables and had an area under the Receiver Operating Characteristic curve of 0.72. In each administrative claims validation cohort, model fit was similar to the derivation cohort. The distribution of standardized mortality rates among hospitals ranged from 13.0% to 23.7%, with 25(th), 50(th), and 75(th) percentiles of 16.5%, 17.4%, and 18.3%, respectively. Comparing model-derived risk-standardized state mortality rates with medical record-derived estimates, the correlation coefficient was 0.86 (Standard Error = 0.032). An administrative claims-based model for profiling hospitals for pneumonia mortality performs consistently over several years and produces hospital estimates close to those using a medical record model.

An Administrative Claims Model for Profiling Hospital 30-Day Mortality Rates for Pneumonia Patients

PubMed Central

Bratzler, Dale W.; Normand, Sharon-Lise T.; Wang, Yun; O'Donnell, Walter J.; Metersky, Mark; Han, Lein F.; Rapp, Michael T.; Krumholz, Harlan M.

2011-01-01

Background Outcome measures for patients hospitalized with pneumonia may complement process measures in characterizing quality of care. We sought to develop and validate a hierarchical regression model using Medicare claims data that produces hospital-level, risk-standardized 30-day mortality rates useful for public reporting for patients hospitalized with pneumonia. Methodology/Principal Findings Retrospective study of fee-for-service Medicare beneficiaries age 66 years and older with a principal discharge diagnosis of pneumonia. Candidate risk-adjustment variables included patient demographics, administrative diagnosis codes from the index hospitalization, and all inpatient and outpatient encounters from the year before admission. The model derivation cohort included 224,608 pneumonia cases admitted to 4,664 hospitals in 2000, and validation cohorts included cases from each of years 1998–2003. We compared model-derived state-level standardized mortality estimates with medical record-derived state-level standardized mortality estimates using data from the Medicare National Pneumonia Project on 50,858 patients hospitalized from 1998–2001. The final model included 31 variables and had an area under the Receiver Operating Characteristic curve of 0.72. In each administrative claims validation cohort, model fit was similar to the derivation cohort. The distribution of standardized mortality rates among hospitals ranged from 13.0% to 23.7%, with 25th, 50th, and 75th percentiles of 16.5%, 17.4%, and 18.3%, respectively. Comparing model-derived risk-standardized state mortality rates with medical record-derived estimates, the correlation coefficient was 0.86 (Standard Error = 0.032). Conclusions/Significance An administrative claims-based model for profiling hospitals for pneumonia mortality performs consistently over several years and produces hospital estimates close to those using a medical record model. PMID:21532758

Parkinson's disease: increased motor network activity in the absence of movement.

PubMed

Ko, Ji Hyun; Mure, Hideo; Tang, Chris C; Ma, Yilong; Dhawan, Vijay; Spetsieris, Phoebe; Eidelberg, David

2013-03-06

We used a network approach to assess systems-level abnormalities in motor activation in humans with Parkinson's disease (PD). This was done by measuring the expression of the normal movement-related activation pattern (NMRP), a previously validated activation network deployed by healthy subjects during motor performance. In this study, NMRP expression was prospectively quantified in (15)O-water PET scans from a PD patient cohort comprised of a longitudinal early-stage group (n = 12) scanned at baseline and at two or three follow-up visits two years apart, and a moderately advanced group scanned on and off treatment with either subthalamic nucleus deep brain stimulation (n = 14) or intravenous levodopa infusion (n = 14). For each subject and condition, we measured NMRP expression during both movement and rest. Resting expression of the abnormal PD-related metabolic covariance pattern was likewise determined in the same subjects. NMRP expression was abnormally elevated (p < 0.001) in PD patients scanned in the nonmovement rest state. By contrast, network activity measured during movement did not differ from normal (p = 0.34). In the longitudinal cohort, abnormal increases in resting NMRP expression were evident at the earliest clinical stages (p < 0.05), which progressed significantly over time (p = 0.003). Analogous network changes were present at baseline in the treatment cohort (p = 0.001). These abnormalities improved with subthalamic nucleus stimulation (p < 0.005) but not levodopa (p = 0.25). In both cohorts, the changes in NMRP expression that were observed did not correlate with concurrent PD-related metabolic covariance pattern measurements (p > 0.22). Thus, the resting state in PD is characterized by changes in the activity of normal as well as pathological brain networks.

Safety of sitagliptin in patients with type 2 diabetes and chronic kidney disease: outcomes from TECOS.

PubMed

Engel, Samuel S; Suryawanshi, Shailaja; Stevens, Susanna R; Josse, Robert G; Cornel, Jan H; Jakuboniene, Neli; Riefflin, Axel; Tankova, Tsvetalina; Wainstein, Julio; Peterson, Eric D; Holman, Rury R

2017-11-01

To characterize the incidence of diabetes-associated complications and assess the safety of sitagliptin in participants with chronic kidney disease (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). For participants with baseline eGFR measurements (n = 14 528), baseline characteristics and safety outcomes were compared for the CKD cohort (eGFR < 60 mL/min per 1.73 m 2 ) vs those without CKD. Within the CKD cohort, the same analyses were performed, comparing sitagliptin- and placebo-assigned participants. Baseline characteristics were summarized for all participants, and serious adverse events were analysed in those who received at least 1 dose of study medication. Adverse events of interest and diabetes complications were summarized for the intention-to-treat population. CKD was present in 3324 (23%) participants at entry into TECOS. The mean (SD) age for this CKD cohort was 68.8 (7.9) years, mean diabetes duration was 13.7 (9.0) years, and 62% were men. Incidences of serious adverse events, malignancy, bone fracture, severe hypoglycaemia and most categories of diabetes complications were higher in the CKD cohort compared with those without CKD. Over ~2.8 median years of follow-up, CKD participants assigned to sitagliptin had rates of diabetic eye disease, diabetic neuropathy, renal failure, malignancy, bone fracture, pancreatitis and severe hypoglycaemia similar to those of placebo-assigned participants. Participants in TECOS with CKD had higher incidences of serious adverse events and diabetes complications than those without CKD. Treatment with sitagliptin was generally well tolerated, with no meaningful differences in safety outcomes observed between those with CKD assigned to sitagliptin or placebo. © 2017 John Wiley & Sons Ltd.

Pattern Recognition Analysis of Age-Related Retinal Ganglion Cell Signatures in the Human Eye

PubMed Central

Yoshioka, Nayuta; Zangerl, Barbara; Nivison-Smith, Lisa; Khuu, Sieu K.; Jones, Bryan W.; Pfeiffer, Rebecca L.; Marc, Robert E.; Kalloniatis, Michael

2017-01-01

Purpose To characterize macular ganglion cell layer (GCL) changes with age and provide a framework to assess changes in ocular disease. This study used data clustering to analyze macular GCL patterns from optical coherence tomography (OCT) in a large cohort of subjects without ocular disease. Methods Single eyes of 201 patients evaluated at the Centre for Eye Health (Sydney, Australia) were retrospectively enrolled (age range, 20–85); 8 × 8 grid locations obtained from Spectralis OCT macular scans were analyzed with unsupervised classification into statistically separable classes sharing common GCL thickness and change with age. The resulting classes and gridwise data were fitted with linear and segmented linear regression curves. Additionally, normalized data were analyzed to determine regression as a percentage. Accuracy of each model was examined through comparison of predicted 50-year-old equivalent macular GCL thickness for the entire cohort to a true 50-year-old reference cohort. Results Pattern recognition clustered GCL thickness across the macula into five to eight spatially concentric classes. F-test demonstrated segmented linear regression to be the most appropriate model for macular GCL change. The pattern recognition–derived and normalized model revealed less difference between the predicted macular GCL thickness and the reference cohort (average ± SD 0.19 ± 0.92 and −0.30 ± 0.61 μm) than a gridwise model (average ± SD 0.62 ± 1.43 μm). Conclusions Pattern recognition successfully identified statistically separable macular areas that undergo a segmented linear reduction with age. This regression model better predicted macular GCL thickness. The various unique spatial patterns revealed by pattern recognition combined with core GCL thickness data provide a framework to analyze GCL loss in ocular disease. PMID:28632847

Characterization of microbiota in male infertility cases uncovers differences in seminal hyperviscosity and oligoasthenoteratozoospermia possibly correlated with increased prevalence of infectious bacteria.

PubMed

Monteiro, Catarina; Marques, Patrícia I; Cavadas, Bruno; Damião, Isabel; Almeida, Vasco; Barros, Nuno; Barros, Alberto; Carvalho, Filipa; Gomes, Sílvia; Seixas, Susana

2018-06-01

Sexually transmitted diseases and other infections of male genitourinary tract are thought to negatively impact reproductive health, affecting semen quality. Despite a possible link between bacteria and infertility, few studies attempted to characterize seminal microbiota in healthy and diseased subjects. A high-throughput sequencing of 16S ribosomal RNA gene was performed in a cohort of infertility-related cases (N = 89) and controls (N = 29) using a pooled sample approach. A global characterization of microbiota was obtained at low cost, without compromising the identification of bacterial taxa. This strategy allowed us to detect changes in the microbiota of infertility-related phenotypes, such as an increment of Proteobacteria in seminal hyperviscosity, and to separate this later group from oligoasthenoteratozoospermia based in bacterial (family/genus) abundances. We provide data for a likely contribution of bacteria into seminal hyperviscosity and oligoasthenoteratozoospermia, partially correlated with an increment of Neisseria, Klebsiella, and Pseudomonas pathogens and a reduction in Lactobacillus probiotic agent. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Low bone mineral mass is associated with decreased bone formation and diet in girls with Rett syndrome.

PubMed

Motil, Kathleen J; Barrish, Judy O; Neul, Jeffrey L; Glaze, Daniel G

2014-09-01

The aim of the present study was to characterize biomarkers of bone turnover and their relation with bone mineral mass in a cross-sectional cohort of girls with Rett syndrome (RTT) and to examine the role of dietary, biochemical, hormonal, and inflammatory factors on bone mineral mass and bone biomarkers in this disorder. Total body bone mineral content (BMC) and bone mineral density (BMD) were determined by dual-energy x-ray absorptiometry. Dietary nutrient intakes were determined from 3-day food records. Biomarkers of bone turnover, bone metabolites, vitamin D metabolites, hormones, and inflammatory markers were measured by standard clinical laboratory methods. Serum osteocalcin, bone alkaline phosphatase, and C-telopeptide showed significant inverse relations with age in the RTT cohort. Mean osteocalcin concentrations were significantly lower and mean bone alkaline phosphatase concentrations were significantly higher for individual age groups in the RTT cohort than mean values for their respective age ranges in the reference population. Significant inverse associations were identified between urinary calcium losses, expressed as calcium:creatinine ratios, and total body BMC and BMD z scores. Dietary protein, calcium, and phosphorus intakes, expressed as a proportion of Dietary Reference Intakes for age and sex, showed significant positive associations with total body BMD z scores. The present study suggests decreased bone formation instead of increased bone resorption may explain in part the deficits in bone mineral mass in RTT and that attention to the adequacy of dietary protein, calcium, and phosphorus intakes may offer an opportunity to improve bone health in RTT.

Effect of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of dolasetron and granisetron.

PubMed

Adams, Laurel M; Johnson, Brendan; Zhang, Ke; Yue, Lin; Kirby, Lyndon C; Lebowitz, Peter; Stoltz, Randall

2009-09-01

The objective of this study was to characterize the impact of casopitant, a novel neurokinin-1 receptor antagonist under investigation for the prevention of postoperative and chemotherapy-induced nausea and vomiting, on the pharmacokinetics of the commonly prescribed 5-hydroxytryptamine receptor 3 receptor antagonists, dolasetron or granisetron. In a phase I, open-label, two-part, two-period, single-sequence study, two cohorts of healthy subjects received either oral dolasetron (100 mg once daily for 3 days) or oral granisetron (2 mg once daily for 3 days) alone (period 1) and combined with oral casopitant, 150 mg day 1, 50 mg days 2 and 3 (period 2). Pharmacokinetics of hydrodolasetron and granisetron were assessed on days 1 and 3 of each period. Log-transformed area under the curve (AUC) and Cmax were statistically analyzed by performing an analysis of variance. Eighteen subjects were enrolled in the dolasetron cohort; nine subjects were CYP2D6 extensive metabolizers (EMs) and nine subjects were CYP2D6 poor metabolizers. Nineteen subjects were enrolled in the granisetron cohort. The largest changes in hydrodolasetron exposure after coadministration with casopitant were seen in CYP2D6 EMs, with a 24% increase in hydrodolasetron AUC on day 1 and 30% increase in Cmax on days 1 and 3. All other changes in hydrodolasetron exposure were <20%, and granisetron exposure was not altered to any relevant extent (<11%). None of the changes observed are considered clinically meaningful, and coadministration of casopitant with dolasetron or granisetron was well tolerated.

Aging Well: Observations From the Women’s Health Initiative Study

PubMed Central

Rillamas-Sun, Eileen; Cochrane, Barbara B.; La Croix, Andrea Z.; Seeman, Teresa E.; Tindle, Hilary A.; Zaslavsky, Oleg; Bird, Chloe E.; Johnson, Karen C.; Manson, JoAnn E.; Ockene, Judith K.; Seguin, Rebecca A.; Wallace, Robert B.

2016-01-01

Abstract Background. As the proportion of the population aged 80 and over accelerates, so does the value of understanding the processes of aging well. The purposes of this article are to: (a) review contemporary theoretical and conceptual perspectives on aging well, (b) describe indicators of aging well that reflect key concepts and perspectives as assessed in the Women’s Health Initiative (WHI) and (c) characterize the status of aging among women aged 80 and older using data obtained from WHI participants at the WHI Extension 2 follow-up. Methods. Data from the Lifestyle Questionnaire, which was administered from 2011 to 2012 during the WHI Follow-up Study (Extension 2), were analyzed to provide a profile of the WHI cohort with respect to aging well. Results. Data revealed substantial diversity in the cohort with respect to the various measures of aging well. Although many reported physical functioning levels consistent with disability, most rated their health as good or better. Most reported moderately high levels of resilience, self-control, and self-mastery but lower levels of environmental mastery. Finally, the cohort reported high levels of optimal aging as reflected by their high levels of emotional well-being and moderately high levels of life satisfaction and social support, but more modest levels of personal growth and purpose in life. Conclusions. The wide range of some dimensions of aging well suggest that further examination of predictors of positive coping and resilience in the face of aging-related disability could identify opportunities to support and facilitate aging well among U.S. women. PMID:26858322

Race and Resting-State Heart Rate Variability in Brazilian Civil Servants and the Mediating Effects of Discrimination: An ELSA-Brasil Cohort Study.

PubMed

Kemp, Andrew H; Koenig, Julian; Thayer, Julian F; Bittencourt, Marcio S; Pereira, Alexandre C; Santos, Itamar S; Dantas, Eduardo M; Mill, José G; Chor, Dora; Ribeiro, Antonio L P; Benseñor, Isabela M; Lotufo, Paulo A

2016-10-01

African Americans are characterized by higher heart rate variability (HRV), a finding ostensibly associated with beneficial health outcomes. However, these findings are at odds with other evidence that blacks have worse cardiovascular outcomes. Here, we examine associations in a large cohort from the ELSA-Brasil study and determined whether these effects are mediated by discrimination. Three groups were compared on the basis of self-declared race: "black" (n = 2,020), "brown" (n = 3,502), and "white" (n = 6,467). Perceived discrimination was measured using a modified version of the Everyday Discrimination Scale. Resting-state HRV was extracted from 10-minute resting-state electrocardiograms. Racial differences in HRV were determined by regression analyses weighted by propensity scores, which controlled for potentially confounding variables including age, sex, education, and other health-related information. Nonlinear mediation analysis quantified the average total effect, comprising direct (race-HRV) and indirect (race-discrimination-HRV) pathways. Black participants displayed higher HRV relative to brown (Cohen's d = 0.20) and white participants (Cohen's d = 0.31). Brown relative to white participants also displayed a small but significantly higher HRV (Cohen's d = 0.14). Discrimination indirectly contributed to the effects of race on HRV. This large cohort from the Brazilian population shows that HRV is greatest in black, followed by brown, relative to white participants. The presence of higher HRV in these groups may reflect a sustained compensatory psychophysiological response to the adverse effects of discrimination. Additional research is needed to determine the health consequences of these differences in HRV across racial and ethnic groups.

Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach.

PubMed

Abdulkadir, Mohamed; Londono, Douglas; Gordon, Derek; Fernandez, Thomas V; Brown, Lawrence W; Cheon, Keun-Ah; Coffey, Barbara J; Elzerman, Lonneke; Fremer, Carolin; Fründt, Odette; Garcia-Delgar, Blanca; Gilbert, Donald L; Grice, Dorothy E; Hedderly, Tammy; Heyman, Isobel; Hong, Hyun Ju; Huyser, Chaim; Ibanez-Gomez, Laura; Jakubovski, Ewgeni; Kim, Young Key; Kim, Young Shin; Koh, Yun-Joo; Kook, Sodahm; Kuperman, Samuel; Leventhal, Bennett; Ludolph, Andrea G; Madruga-Garrido, Marcos; Maras, Athanasios; Mir, Pablo; Morer, Astrid; Müller-Vahl, Kirsten; Münchau, Alexander; Murphy, Tara L; Plessen, Kerstin J; Roessner, Veit; Shin, Eun-Young; Song, Dong-Ho; Song, Jungeun; Tübing, Jennifer; van den Ban, Els; Visscher, Frank; Wanderer, Sina; Woods, Martin; Zinner, Samuel H; King, Robert A; Tischfield, Jay A; Heiman, Gary A; Hoekstra, Pieter J; Dietrich, Andrea

2018-04-01

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent-child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case-control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes.

Potential Adverse Effects of Broad-Spectrum Antimicrobial Exposure in the Intensive Care Unit.

PubMed

Wiens, Jenna; Snyder, Graham M; Finlayson, Samuel; Mahoney, Monica V; Celi, Leo Anthony

2018-02-01

The potential adverse effects of empiric broad-spectrum antimicrobial use among patients with suspected but subsequently excluded infection have not been fully characterized. We sought novel methods to quantify the risk of adverse effects of broad-spectrum antimicrobial exposure among patients admitted to an intensive care unit (ICU). Among all adult patients admitted to ICUs at a single institution, we selected patients with negative blood cultures who also received ≥1 broad-spectrum antimicrobials. Broad-spectrum antimicrobials were categorized in ≥1 of 5 categories based on their spectrum of activity against potential pathogens. We performed, in serial, 5 cohort studies to measure the effect of each broad-spectrum category on patient outcomes. Exposed patients were defined as those receiving a specific category of broad-spectrum antimicrobial; nonexposed were all other patients in the cohort. The primary outcome was 30-day mortality. Secondary outcomes included length of hospital and ICU stay and nosocomial acquisition of antimicrobial-resistant bacteria (ARB) or Clostridium difficile within 30 days of admission. Among the study cohort of 1918 patients, 316 (16.5%) died within 30 days, 821 (42.8%) had either a length of hospital stay >7 days or an ICU length of stay >3 days, and 106 (5.5%) acquired either a nosocomial ARB or C. difficile . The short-term use of broad-spectrum antimicrobials in any of the defined broad-spectrum categories was not significantly associated with either primary or secondary outcomes. The prompt and brief empiric use of defined categories of broad-spectrum antimicrobials could not be associated with additional patient harm.

Cardiorespiratory fitness and the risk of overweight in youth: the Healthy Hearts Longitudinal Study of Cardiometabolic Health.

PubMed

McGavock, Jonathan M; Torrance, Brian D; McGuire, K Ashlee; Wozny, Paul D; Lewanczuk, Richard Z

2009-09-01

The primary objective of this longitudinal study was to determine the association between cardiorespiratory fitness and the risk of overweight status in youth. To accomplish this aim we analyzed data from annual school-based surveys of cardiorespiratory fitness and anthropometry conducted between 2004 and 2006. The first analysis was performed on a cohort of 902 youth aged 6-15 years followed for 12 months to assess the association between cardiorespiratory fitness levels determined from a graded maximal field test and the risk of becoming overweight. The second analysis was conducted on a cohort of 222 youth followed for 2 years to assess the continuous association between annual changes fitness and weight gain. Children with low cardiorespiratory fitness were characterized by higher waist circumference and disproportionate weight gain over the 12-month follow-up period (P < 0.05). Within the entire cohort, the 12-month risk of overweight classification was 3.5-fold (95% confidence = 2.0-6.0, P < 0.001) higher in youth with low cardiorespiratory fitness, relative to fit peers. A time series mixed effects regression model revealed that reductions in cardiorespiratory fitness were significantly and independently associated with increasing BMI (r = -0.18, P < 0.05) in youth. Accordingly, low cardiorespiratory fitness and reductions in fitness over time are significantly associated with weight gain and the risk of overweight in children 6-15 years old. An assessment of cardiorespiratory fitness using a common field test may prove useful for the identification of youth at risk of overweight and serve as a potential target for obesity prevention.

Follow-up methods for retrospective cohort studies in New Zealand.

PubMed

Fawcett, Jackie; Garrett, Nick; Bates, Michael N

2002-01-01

To define a general methodology for maximising the success of follow-up processes for retrospective cohort studies in New Zealand, and to illustrate an approach to developing country-specific follow-up methodologies. We recently conducted a cohort study of mortality and cancer incidence in New Zealand professional fire fighters. A number of methods were used to trace vital status, including matching with records of the New Zealand Health Information Service (NZHIS), pension records of Work and Income New Zealand (WINZ), and electronic electoral rolls. Non-electronic methods included use of paper electoral rolls and the records of the Registrar of Births Deaths and Marriages. 95% of the theoretical person-years of follow-up of the cohort were traced using these methods. In terms of numbers of cohort members traced to end of follow-up, the most useful tracing methods were fire fighter employment records, the NZHIS, WINZ, and the electronic electoral rolls. The follow-up process used for the cohort study was highly successful. On the basis of this experience, we propose a generic, but flexible, model for follow-up of retrospective cohort studies in New Zealand. Similar models could be constructed for other countries. Successful follow-up of cohort studies is possible in New Zealand using established methods. This should encourage the use of cohort studies for the investigation of epidemiological issues. Similar models for follow-up processes could be constructed for other countries.

Predictors of Breastmilk Expression by 1 Month Postpartum and Influence on Breastmilk Feeding Duration

PubMed Central

Davidson, Barbara; Tabangin, Meredith; Morrow, Ardythe

2012-01-01

Abstract Objective This study was designed to determine which factors characterize mothers who expressed their milk by the end of 4 weeks postpartum as well as the duration for which they continued any breastmilk feeding. Methods This prospective longitudinal cohort study was conducted with women who donated their milk and clinical data to the Cincinnati Children's Research Human Milk Bank (Cincinnati, OH). We examined the characteristics and length of breastmilk feeding of mothers who expressed their milk within the first month postpartum compared with those mothers who only fed directly at the breast. Results By the end of the first 4 weeks postpartum, 63% (37 of 59) of the mothers had begun milk expression. Predictors of milk expression by 1 month were planned work by 6 months, lower infant birth weight, and higher maternal body mass index. Milk expression by 4 weeks did not significantly influence duration of breastmilk feeding. Conclusions Breastmilk expression in this cohort was common even within the first month postpartum before mothers in the United States typically go back to work. “Breastfeeding” classification needs to be updated to include options for breastmilk expression so the appropriate study of health outcomes related to this practice can be determined. PMID:21777073

Clinical evaluation of Morgellons disease in a cohort of North American patients

PubMed Central

Fesler, Melissa C.; Middelveen, Marianne J.; Stricker, Raphael B.

2018-01-01

Morgellons disease (MD) is a dermatological condition characterized by aberrant production of keratin and collagen fibers in skin. Although infection with Borrelia burgdorferi, the causative agent of Lyme disease (LD), has been associated with MD, relatively few studies have hitherto provided epidemiological evidence regarding this association. A cohort of 1000 seropositive North American LD patients was evaluated for the presence of MD. Patients were diagnosed with MD based on detection of microscopic fibers in skin lesions or under unbroken skin. Demographic and clinical features of MD patients were analyzed, and laboratory testing for tickborne coinfections and other infectious agents, was performed. Subjective and objective features of MD were analyzed using statistical methods. Of 1000 seropositive LD patients, 60 (6%) were diagnosed with MD. Of these 60 patients, 75% were female and 78% presented in the late disseminated stage of MD. All 60 patients (100%) were seropositive for B. burgdorferi infection. Tickborne coinfections in these patients included Babesia spp (62%), Bartonella and Rickettsia (25% each), Ehrlichia (15%) and Anaplasma (10%). Helicobacter pylori was detected in 12% of MD patients. In all, 77% of MD patients had one or more coinfections. This study confirms recent findings that MD occurs in a limited subset of LD patients. The clinical and genetic determinants of MD in LD patients require further study. PMID:29774138

Clinical evaluation of Morgellons disease in a cohort of North American patients.

PubMed

Fesler, Melissa C; Middelveen, Marianne J; Stricker, Raphael B

2018-04-23

Morgellons disease (MD) is a dermatological condition characterized by aberrant production of keratin and collagen fibers in skin. Although infection with Borrelia burgdorferi , the causative agent of Lyme disease (LD), has been associated with MD, relatively few studies have hitherto provided epidemiological evidence regarding this association. A cohort of 1000 seropositive North American LD patients was evaluated for the presence of MD. Patients were diagnosed with MD based on detection of microscopic fibers in skin lesions or under unbroken skin. Demographic and clinical features of MD patients were analyzed, and laboratory testing for tickborne coinfections and other infectious agents, was performed. Subjective and objective features of MD were analyzed using statistical methods. Of 1000 seropositive LD patients, 60 (6%) were diagnosed with MD. Of these 60 patients, 75% were female and 78% presented in the late disseminated stage of MD. All 60 patients (100%) were seropositive for B. burgdorferi infection. Tickborne coinfections in these patients included Babesia spp (62%), Bartonella and Rickettsia (25% each), Ehrlichia (15%) and Anaplasma (10%). Helicobacter pylori was detected in 12% of MD patients. In all, 77% of MD patients had one or more coinfections. This study confirms recent findings that MD occurs in a limited subset of LD patients. The clinical and genetic determinants of MD in LD patients require further study.

Ocular toxoplasmosis: adverse reactions to treatment in a Brazilian cohort.

PubMed

Guaraldo, Lusiele; Villar, Bianca Balzano de la Fuente; Durão, Nicolle Marins Gomes; Louro, Virgínia Clare; Quintana, Marcel de Souza Borges; Curi, André Luiz Land; Neves, Elizabeth Souza

2018-05-19

The purpose of this study was to estimate the frequency and describe the adverse drug reactions (ADRs) associated with the classic treatment of ocular toxoplasmosis (OT), namely sulfadiazine, pyrimethamine, corticosteroids and folinic acid. We performed a descriptive study of a prospective cohort of patients with OT treated with the classic therapy. Data were collected during medical consultations and treatment. Of the 147 patients studied, 85% developed one or more ADR. Women presented more ADRs than men (95% vs 77%). Of the total reactions (n=394), 82% were mild, but we found one life-threatening event (Stevens-Johnson syndrome). The most frequent types (71%) of ADRs were gastrointestinal, skin and neurological or psychiatric. The majority of ADRs (90.3%) occurred before the second week of treatment. A third of the patients were treated for the ADR and 10% dropped out of OT treatment. Most (70%) of the ADRs were characterized as being probably caused by the drugs and may be associated with prednisone, sulfadiazine and sulfadiazine/prednisone. Six percent of ADRs were not previously described, such as taste alteration, constipation/bloating, dyspnoea, sweating and somnolence. Our results suggest a high rate of ADRs to OT classic treatment, which requires careful follow-up in order to identify and treat ADRs early.

Use of remotely sensed data to evaluate the relationship between living environment and blood pressure.

PubMed

Estes, Maurice G; Al-Hamdan, Mohammad Z; Crosson, William; Estes, Sue M; Quattrochi, Dale; Kent, Shia; McClure, Leslie Ain

2009-12-01

Urbanization has been correlated with hypertension (HTN) in developing countries undergoing rapid economic and environmental transitions. We examined the relationships among living environment (urban, suburban, and rural), day/night land surface temperatures (LST), and blood pressure in selected regions from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Also, the linking of data on blood pressure from REGARDS with National Aeronautics and Space Administration (NASA) science data is relevant to NASA's strategic goals and missions, particularly as a primary focus of the agency's Applied Sciences Program. REGARDS is a national cohort of 30,228 people from the 48 contiguous United States with self-reported and measured blood pressure levels. Four metropolitan regions (Philadelphia, PA; Atlanta, GA; Minneapolis, MN; and Chicago, IL) with varying geographic and health characteristics were selected for study. Satellite remotely sensed data were used to characterize the LST and land cover/land use (LCLU) environment for each area. We developed a method for characterizing participants as living in urban, suburban, or rural living environments, using the LCLU data. These data were compiled on a 1-km grid for each region and linked with the REGARDS data via an algorithm using geocoding information. REGARDS participants in urban areas have higher systolic and diastolic blood pressure than do those in suburban or rural areas, and also a higher incidence of HTN. In univariate models, living environment is associated with HTN, but after adjustment for known HTN risk factors, the relationship was no longer present. Further study regarding the relationship between HTN and living environment should focus on additional environmental characteristics, such as air pollution. The living environment classification method using remotely sensed data has the potential to facilitate additional research linking environmental variables to public health concerns.

Association of Serum Vitamin D with the Risk of Incident Dementia and Subclinical Indices of Brain Aging: The Framingham Heart Study.

PubMed

Karakis, Ioannis; Pase, Matthew P; Beiser, Alexa; Booth, Sarah L; Jacques, Paul F; Rogers, Gail; DeCarli, Charles; Vasan, Ramachandran S; Wang, Thomas J; Himali, Jayandra J; Annweiler, Cedric; Seshadri, Sudha

2016-01-01

Identifying nutrition- and lifestyle-based risk factors for cognitive impairment and dementia may aid future primary prevention efforts. We aimed to examine the association of serum vitamin D levels with incident all-cause dementia, clinically characterized Alzheimer's disease (AD), MRI markers of brain aging, and neuropsychological function. Framingham Heart Study participants had baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations measured between 1986 and 2001. Vitamin D status was considered both as a continuous variable and dichotomized as deficient (<10 ng/mL), or at the cohort-specific 20th and 80th percentiles. Vitamin D was related to the 9-year risk of incident dementia (n = 1663), multiple neuropsychological tests (n = 1291) and MRI markers of brain volume, white matter hyperintensities and silent cerebral infarcts (n = 1139). In adjusted models, participants with vitamin D deficiency (n = 104, 8% of the cognitive sample) displayed poorer performance on Trail Making B-A (β= -0.03 to -0.05±0.02) and the Hooper Visual Organization Test (β= -0.09 to -0.12±0.05), indicating poorer executive function, processing speed, and visuo-perceptual skills. These associations remained when vitamin D was examined as a continuous variable or dichotomized at the cohort specific 20th percentile. Vitamin D deficiency was also associated with lower hippocampal volumes (β= -0.01±0.01) but not total brain volume, white matter hyperintensities, or silent brain infarcts. No association was found between vitamin D deficiency and incident all-cause dementia or clinically characterized AD. In this large community-based sample, low 25(OH)D concentrations were associated with smaller hippocampal volume and poorer neuropsychological function.

Cohort profile: cerebral palsy in the Norwegian and Danish birth cohorts (MOBAND-CP)

PubMed Central

Tollånes, Mette C; Strandberg-Larsen, Katrine; Forthun, Ingeborg; Petersen, Tanja Gram; Moster, Dag; Andersen, Anne-Marie Nybo; Stoltenberg, Camilla; Olsen, Jørn; Wilcox, Allen J

2016-01-01

Purpose The purpose of MOthers and BAbies in Norway and Denmark cerebral palsy (MOBAND-CP) was to study CP aetiology in a prospective design. Participants MOBAND-CP is a cohort of more than 210 000 children, created as a collaboration between the world's two largest pregnancy cohorts—the Norwegian Mother and Child Cohort study (MoBa) and the Danish National Birth Cohort. MOBAND-CP includes maternal interview/questionnaire data collected during pregnancy and follow-up, plus linked information from national health registries. Findings to date Initial harmonisation of data from the 2 cohorts has created 140 variables for children and their mothers. In the MOBAND-CP cohort, 438 children with CP have been identified through record linkage with validated national registries, providing by far the largest such sample with prospectively collected detailed pregnancy data. Several studies investigating various hypotheses regarding CP aetiology are currently on-going. Future plans Additional data can be harmonised as necessary to meet requirements of new projects. Biological specimens collected during pregnancy and at delivery are potentially available for assay, as are results from assays conducted on these specimens for other projects. The study size allows consideration of CP subtypes, which is rare in aetiological studies of CP. In addition, MOBAND-CP provides a platform within the context of a merged birth cohort of exceptional size that could, after appropriate permissions have been sought, be used for cohort and case-cohort studies of other relatively rare health conditions of infants and children. PMID:27591025

Detection and characterization of interleukin-6 gene variants in Canis familiaris: association studies with periodontal disease.

PubMed

Morinha, Francisco; Albuquerque, Carlos; Requicha, João; Dias, Isabel; Leitão, José; Gut, Ivo; Guedes-Pinto, Henrique; Viegas, Carlos; Bastos, Estela

2011-10-10

Periodontal disease (PD) is the most common inflammatory disease of the oral cavity of domestic carnivores. In Human Medicine molecular genetics research showed that several genes play a role in the predisposition and progression of this complex disease, primarily through the regulation of inflammatory mediators, but the exactly mechanisms are poorly understood. This study aims to contribute to the characterization of the genetic basis of PD in the dog, a classically accepted model in Periodontology. We searched for genetic variations in the interleukin-6 (IL6) gene, in order to verify its association with PD in a case-control study including 25 dogs in the PD case group and 45 dogs in the control group. We indentified and characterized three new genetic variations in IL6 gene. No statistically significant differences were detected between the control and PD cases groups. Our results do not support an evidence for a major role contribution of these variants in the susceptibility to PD in the analyzed population. Nevertheless, the sequence variant I/5_g.105G>A leads to an amino acid change (arginine to glutamine) and was predicted to be possibly damaging to the IL6 protein. A larger cohort and functional studies would be of extreme importance in a near future to understand the possible role of IL6 variants in this disease. Copyright © 2011 Elsevier B.V. All rights reserved.

The Dresden Burnout Study: Protocol of a prospective cohort study for the bio-psychological investigation of burnout.

PubMed

Penz, Marlene; Wekenborg, Magdalena K; Pieper, Lars; Beesdo-Baum, Katja; Walther, Andreas; Miller, Robert; Stalder, Tobias; Kirschbaum, Clemens

2018-06-01

The Dresden Burnout Study (DBS) is a 12-year longitudinal cohort study that aims to provide a description of the burnout syndrome on the basis of time and symptom criteria with a special focus on the search for biomarkers. Biological and psychosocial approaches are applied to examine the long-term course and consequences of burnout within a population-based German-speaking sample aged 18 to 68 years. Demographics and psychosocial data are generated by online assessments, including demographics and questionnaires on burnout, burnout-related constructs, work-environment, and health-related factors. The lab-based biomarker assessment includes endocrine, physiological, immunological, and epigenetic markers obtained from blood and hair samples. In addition, heart rate variability is also measured repeatedly. Within the first 2 years, the DBS collected psychosocial data from over 7,600 participants with biological data obtained from more than 800 individuals. During the following 10 years, detailed assessments of biomarkers and psychosocial factors will be collected in annual study waves. Results will be generated during the following decade. The findings of the DBS are expected to pave the road for an in-depth biopsychosocial characterization of burnout and to give insight into the long-term course and potential mental and physical health consequences of the burnout syndrome. Copyright © 2018 John Wiley & Sons, Ltd.

EU-AIMS Longitudinal European Autism Project (LEAP): the autism twin cohort.

PubMed

Isaksson, Johan; Tammimies, Kristiina; Neufeld, Janina; Cauvet, Élodie; Lundin, Karl; Buitelaar, Jan K; Loth, Eva; Murphy, Declan G M; Spooren, Will; Bölte, Sven

2018-01-01

EU-AIMS is the largest European research program aiming to identify stratification biomarkers and novel interventions for autism spectrum disorder (ASD). Within the program, the Longitudinal European Autism Project (LEAP) has recruited and comprehensively phenotyped a rare sample of 76 monozygotic and dizygotic twins, discordant, or concordant for ASD plus 30 typically developing twins. The aim of this letter is to complete previous descriptions of the LEAP case-control sample, clinically characterize, and investigate the suitability of the sample for ASD twin-control analyses purposes and share some 'lessons learnt.' Among the twins, a diagnosis of ASD is associated with increased symptom levels of ADHD, higher rates of intellectual disability, and lower family income. For the future, we conclude that the LEAP twin cohort offers multiple options for analyses of genetic and shared and non-shared environmental factors to generate new hypotheses for the larger cohort of LEAP singletons, but particularly cross-validate and refine evidence from it.

Impact of Cohort Bonds on Student Satisfaction and Engagement

ERIC Educational Resources Information Center

Martin, Kimberly A.; Goldwasser, Molly M.; Galentino, Richard

2017-01-01

This study examines differences in student satisfaction and engagement in cohort programs versus traditional, non-cohort educational programs by studying the impact of close bonds between students. The authors measure and compare "close bonds" within an educational cohort to a traditional program and measure the impact of close bonds on…

Spectrum and Prevalence of CALM1-, CALM2-, and CALM3-Encoded Calmodulin (CaM) Variants in Long QT Syndrome (LQTS) and Functional Characterization of a Novel LQTS-Associated CaM Missense Variant, E141G

PubMed Central

Calvert, Melissa L.; Tester, David J.; Kryshtal, Dmytro; Hwang, Hyun Seok; Johnson, Christopher N.; Chazin, Walter J.; Loporcaro, Christina G.; Shah, Maully; Papez, Andrew L.; Lau, Yung R.; Kanter, Ronald; Knollmann, Bjorn C.; Ackerman, Michael J.

2016-01-01

Background Calmodulin (CaM) is encoded by three genes, CALM1, CALM2, and CALM3, all of which harbor pathogenic variants linked to long QT syndrome (LQTS) with early and severe expressivity. These LQTS-causative variants reduce CaM affinity to Ca2+ and alter the properties of the cardiac L-type calcium channel (CaV1.2). CaM also modulates NaV1.5 and the ryanodine receptor, RyR2. All of these interactions may play a role in disease pathogenesis. Here, we determine the spectrum and prevalence of pathogenic CaM variants in a cohort of genetically elusive LQTS, and functionally characterize the novel variants. Methods and Results Thirty-nine genetically elusive LQTS cases underwent whole exome sequencing to identify CaM variants. Non-synonymous CaM variants were overrepresented significantly in this heretofore LQTS cohort (15.4%) compared to exome aggregation consortium (0.04%; p<0.0001). When the clinical sequelae of these 6 CaM-positive cases was compared to the 33 CaM-negative cases, CaM-positive cases had a more severe phenotype with an average age of onset of 8 months, an average QTc of 679 ms, and a high prevalence of cardiac arrest. Functional characterization of one novel variant, E141G-CaM, revealed an 11-fold reduction in Ca2+ binding affinity and a functionally-dominant loss of inactivation in CaV1.2, mild accentuation in NaV1.5 late current, but no effect on intracellular RyR2-mediated calcium release. Conclusions Overall, 15% of our genetically elusive LQTS cohort harbored non-synonymous variants in CaM. Genetic testing of CALM1-3 should be pursued for individuals with LQTS, especially those with early childhood cardiac arrest, extreme QT prolongation, and a negative family history. PMID:26969752

Serum C-X-C motif chemokine 13 is elevated in early and established rheumatoid arthritis and correlates with rheumatoid factor levels

PubMed Central

2014-01-01

Introduction We hypothesized that serum levels of C-X-C motif chemokine 13 (CXCL13), a B-cell chemokine, would delineate a subset of rheumatoid arthritis (RA) patients characterized by increased humoral immunity. Methods Serum from patients with established RA (the Dartmouth RA Cohort) was analyzed for CXCL13, rheumatoid factor (RF) levels, anticitrullinated peptide/protein antibody (ACPA) and total immunoglobulin G (IgG); other parameters were obtained by chart review. A confirmatory analysis was performed using samples from the Sherbrooke Early Undifferentiated PolyArthritis (EUPA) Cohort. The Wilcoxon rank-sum test, a t-test and Spearman’s correlation analysis were utilized to determine relationships between variables. Results In both the Dartmouth and Sherbrooke cohorts, CXCL13 levels were selectively increased in seropositive relative to seronegative RA patients (P = 0.0002 and P < 0.0001 for the respective cohorts), with a strong correlation to both immunoglobulin M (IgM) and IgA RF levels (P < 0.0001). There was a weaker relationship to ACPA titers (P = 0.03 and P = 0.006, respectively) and total IgG (P = 0.02 and P = 0.14, respectively). No relationship was seen with regard to age, sex, shared epitope status or inclusion high-sensitivity C-reactive protein (hsCRP) in either cohort or regarding the presence of baseline erosions in the Sherbrooke Cohort, whereas a modest relationship with Disease Activity Score in 28 joints CRP (DAS28-CRP) was seen in the Dartmouth cohort but not the Sherbrooke cohort. Conclusion Using both established and early RA cohorts, marked elevations of serum CXCL13 levels resided nearly completely within the seropositive population. CXCL13 levels exhibited a strong relationship with RF, whereas the association with clinical parameters (age, sex, DAS28-CRP and erosions) or other serologic markers (ACPA and IgG) was either much weaker or absent. Elevated serum CXCL13 levels may identify a subset of seropositive RA patients whose disease is shaped by or responsive to RF production. PMID:24766912

What is the relationship between type 2 diabetes mellitus status and the neuroradiological correlates of cerebral small vessel disease in adults? Protocol for a systematic review.

PubMed

Funnell, Clark; Doyle-Waters, Mary M; Yip, Samuel; Field, Thalia

2017-01-17

Cerebral small vessel disease (CSVD) is a common cause of stroke, dementia, and functional decline. In recent years, neuroradiologic correlates of CSVD have been identified. These imaging findings, best characterized on magnetic resonance imaging (MRI), include some combination of white matter hyperintensities, lacunes, cerebral microbleeds, enlarged perivascular spaces, and cerebral atrophy. Though some cohorts have reported that participants with type 2 diabetes mellitus (T2DM), an important risk factor for CSVD, may have a distinct neuroradiologic phenotype, this relationship is not well-characterized. Adults with diabetes mellitus have a two- to threefold higher incidence of ischemic stroke compared to controls and are an increasingly important population given global trends of increasing diabetes prevalence. This study aims to determine if adults with CSVD and T2DM have a distinct neuroradiologic phenotype. A systematic search of the literature will be conducted to find articles that report the MRI features of CSVD in a cohort of participants including those with and without type 2 diabetes mellitus (T2DM). A number of databases will be searched including MEDLINE, Embase, CINAHL, and Web of Science. Proceedings and abstracts from key conferences will also be reviewed and relevant journals hand searched for additional papers. The references from selected papers will be scanned. Screening of potential articles, data extraction, and quality appraisal will be performed in duplicate by independent reviewers. Odds ratios and 95% confidence intervals for the presence versus absence of each neuroradiologic correlate of interest from each included study will be calculated. If sufficient homogeneity exists among studies, a meta-analysis will be performed for each neuroradiologic correlate of CSVD. If heterogeneity of studies precludes data pooling, results will be presented in narrative form. Determining whether a distinct neuroradiologic phenotype of CSVD exists in adults with T2DM will provide insight into the underlying mechanisms of CSVD and guide future research on therapeutic targets. PROSPERO CRD42016046669.

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.

Cohort profile: cerebral palsy in the Norwegian and Danish birth cohorts (MOBAND-CP).

PubMed

Tollånes, Mette C; Strandberg-Larsen, Katrine; Forthun, Ingeborg; Petersen, Tanja Gram; Moster, Dag; Andersen, Anne-Marie Nybo; Stoltenberg, Camilla; Olsen, Jørn; Wilcox, Allen J

2016-09-02

The purpose of MOthers and BAbies in Norway and Denmark cerebral palsy (MOBAND-CP) was to study CP aetiology in a prospective design. MOBAND-CP is a cohort of more than 210 000 children, created as a collaboration between the world's two largest pregnancy cohorts-the Norwegian Mother and Child Cohort study (MoBa) and the Danish National Birth Cohort. MOBAND-CP includes maternal interview/questionnaire data collected during pregnancy and follow-up, plus linked information from national health registries. Initial harmonisation of data from the 2 cohorts has created 140 variables for children and their mothers. In the MOBAND-CP cohort, 438 children with CP have been identified through record linkage with validated national registries, providing by far the largest such sample with prospectively collected detailed pregnancy data. Several studies investigating various hypotheses regarding CP aetiology are currently on-going. Additional data can be harmonised as necessary to meet requirements of new projects. Biological specimens collected during pregnancy and at delivery are potentially available for assay, as are results from assays conducted on these specimens for other projects. The study size allows consideration of CP subtypes, which is rare in aetiological studies of CP. In addition, MOBAND-CP provides a platform within the context of a merged birth cohort of exceptional size that could, after appropriate permissions have been sought, be used for cohort and case-cohort studies of other relatively rare health conditions of infants and children. 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/

Replication of Rubella Vaccine Population Genetic Studies: Validation of HLA Genotype and Humoral Response Associations

PubMed Central

Ovsyannikova, Inna G.; Jacobson, Robert M.; Vierkant, Robert A.; O’Byrne, Megan M.; Poland, Gregory A.

2009-01-01

Purported genetic associations found in population studies require validation for confirmation. We previously reported rubella vaccine-induced immune responses and HLA associations in 346 adolescents, age 12–18 years (1st cohort), following two doses of a rubella-containing vaccine. We sought to replicate the associations discovered in that work by verifying these associations in a new cohort of 396 subjects, age 11–19 years (2nd cohort), all having had two doses of a rubella-containing vaccine. We found that B*2705 (median 1st cohort 20.9 IU/ml, p=0.028; 2nd cohort 20.5 IU/ml, p=0.001) and DPA1*0201 (median 1st cohort 32.5 IU/ml, p=0.048; 2nd cohort 25.8 IU/ml, p=0.025) alleles were consistently associated with lower rubella-induced antibodies. Further, DPB1*0401 (median 1st cohort 43.5 IU/ml, p=0.021; 2nd cohort 36.2 IU/ml, p=0.002) alleles were associated with higher antibody levels in both populations. The association of DRB1*04-DQB1*03-DPB1*03 (mean 1st cohort 25.2 IU/ml, p=0.011; 2nd cohort 21.4 IU/ml, p=0.032) and DRB1*15/16-DQB1*06-DPB1*03 (1st cohort 16.3 IU/ml, p=0.043; 2nd cohort 19.1 IU/ml, p=0.023) haplotypes with lower rubella-specific antibodies were observed in both studies. This study provides confirmatory evidence for an association between specific class I and II HLA markers and haplotypes with rubella vaccine-induced humoral responses and lends further weight to their influence on rubella immune responses. PMID:19761839

Air Pollution and Nonmalignant Respiratory Mortality in 16 Cohorts within the ESCAPE Project

PubMed Central

Dimakopoulou, Konstantina; Samoli, Evangelia; Beelen, Rob; Stafoggia, Massimo; Andersen, Zorana Jovanovic; Hoffmann, Barbara; Fischer, Paul; Nieuwenhuijsen, Mark; Vineis, Paolo; Xun, Wei; Hoek, Gerard; Raaschou-Nielsen, Ole; Oudin, Anna; Forsberg, Bertil; Modig, Lars; Jousilahti, Pekka; Lanki, Timo; Turunen, Anu; Oftedal, Bente; Nafstad, Per; Schwarze, Per E.; Penell, Johanna; Fratiglioni, Laura; Andersson, Niklas; Pedersen, Nancy; Korek, Michal; De Faire, Ulf; Eriksen, Kirsten Thorup; Tjønneland, Anne; Becker, Thomas; Wang, Meng; Bueno-de-Mesquita, Bas; Tsai, Ming-Yi; Eeftens, Marloes; Peeters, Petra H.; Meliefste, Kees; Marcon, Alessandro; Krämer, Ursula; Kuhlbusch, Thomas A.J.; Vossoughi, Mohammad; Key, Timothy; de Hoogh, Kees; Hampel, Regina; Peters, Annette; Heinrich, Joachim; Weinmayr, Gudrun; Concin, Hans; Nagel, Gabriele; Ineichen, Alex; Jacquemin, Bénédicte; Stempfelet, Morgane; Vilier, Alice; Ricceri, Fulvio; Sacerdote, Carlotta; Pedeli, Xanthi; Katsoulis, Michalis; Trichopoulou, Antonia; Brunekreef, Bert

2014-01-01

Rationale: Prospective cohort studies have shown that chronic exposure to particulate matter and traffic-related air pollution is associated with reduced survival. However, the effects on nonmalignant respiratory mortality are less studied, and the data reported are less consistent. Objectives: We have investigated the relationship of long-term exposure to air pollution and nonmalignant respiratory mortality in 16 cohorts with individual level data within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE). Methods: Data from 16 ongoing cohort studies from Europe were used. The total number of subjects was 307,553. There were 1,559 respiratory deaths during follow-up. Measurements and Main Results: Air pollution exposure was estimated by land use regression models at the baseline residential addresses of study participants and traffic-proximity variables were derived from geographical databases following a standardized procedure within the ESCAPE study. Cohort-specific hazard ratios obtained by Cox proportional hazard models from standardized individual cohort analyses were combined using metaanalyses. We found no significant associations between air pollution exposure and nonmalignant respiratory mortality. Most hazard ratios were slightly below unity, with the exception of the traffic-proximity indicators. Conclusions: In this study of 16 cohorts, there was no association between air pollution exposure and nonmalignant respiratory mortality. PMID:24521254

Characterization of Aryl Hydrocarbon Receptor Interacting Protein (AIP) Mutations in Familial Isolated Pituitary Adenoma Families

PubMed Central

Igreja, Susana; Chahal, Harvinder S; King, Peter; Bolger, Graeme B; Srirangalingam, Umasuthan; Guasti, Leonardo; Chapple, J Paul; Trivellin, Giampaolo; Gueorguiev, Maria; Guegan, Katie; Stals, Karen; Khoo, Bernard; Kumar, Ajith V; Ellard, Sian; Grossman, Ashley B; Korbonits, Márta

2010-01-01

Familial isolated pituitary adenoma (FIPA) is an autosomal dominant condition with variable genetic background and incomplete penetrance. Germline mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene have been reported in 15–40% of FIPA patients. Limited data are available on the functional consequences of the mutations or regarding the regulation of the AIP gene. We describe a large cohort of FIPA families and characterize missense and silent mutations using minigene constructs, luciferase and β-galactosidase assays, as well as in silico predictions. Patients with AIP mutations had a lower mean age at diagnosis (23.6±11.2 years) than AIP mutation-negative patients (40.4±14.5 years). A promoter mutation showed reduced in vitro activity corresponding to lower mRNA expression in patient samples. Stimulation of the protein kinase A-pathway positively regulates the AIP promoter. Silent mutations led to abnormal splicing resulting in truncated protein or reduced AIP expression. A two-hybrid assay of protein–protein interaction of all missense variants showed variable disruption of AIP-phosphodiesterase-4A5 binding. In summary, exonic, promoter, splice-site, and large deletion mutations in AIP are implicated in 31% of families in our FIPA cohort. Functional characterization of AIP changes is important to identify the functional impact of gene sequence variants. Hum Mutat 31:1–11, 2010. © 2010 Wiley-Liss, Inc. PMID:20506337

Investing in Prospective Cohorts for Etiologic Study of Occupational Exposures

PubMed Central

Blair, A.; Hines, C.J.; Thomas, K.W.; Alavanja, M.C.R.; Beane Freeman, L.E.; Hoppin, J.A.; Kamel, F.; Lynch, C.F.; Lubin, J.H.; Silverman, D.T.; Whelan, E.; Zahm, S. H.; Sandler, D. P.

2015-01-01

Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings. Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures. PMID:25603935

Screening for the C9ORF72 repeat expansion in a greek frontotemporal dementia cohort.

PubMed

Kartanou, Chrisoula; Karadima, Georgia; Koutsis, Georgios; Breza, Marianthi; Papageorgiou, Sokratis G; Paraskevas, George P; Kapaki, Elisabeth; Panas, Marios

2018-02-01

The C9orf72 repeat expansion is a common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) in European populations. A previous study has reported a high frequency of the expansion in Greek ALS. However, no data have been reported on the frequency of the expansion in Greek FTD. Currently, we investigated the frequency of the C9orfF72 expansion in a well-characterized cohort of 64 Greek FTD patients. We detected the C9orf72 repeat expansion in 9.3% of cases. Overall, 27.7% of familial and 2.2% of sporadic cases were expansion-positive. Five out of 6 cases had a diagnosis of behavioral variant FTD. All expansion-positive cases had fairly typical FTD presentations. Clinical features included motor neuron disease, Parkinsonism and hallucinations. We conclude that the overall frequency of C9orf72-positive cases in Greek FTD is high, comparable to Greek ALS, similar to some Western European, but significantly higher than some Mediterranean FTD populations.

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

Twenty novel mutations in BCKDHA, BCKDHB and DBT genes in a cohort of 52 Saudi Arabian patients with maple syrup urine disease.

PubMed

Imtiaz, Faiqa; Al-Mostafa, Abeer; Allam, Rabab; Ramzan, Khushnooda; Al-Tassan, Nada; Tahir, Asma I; Al-Numair, Nouf S; Al-Hamed, Mohamed H; Al-Hassnan, Zuhair; Al-Owain, Mohammad; Al-Zaidan, Hamad; Al-Amoudi, Mohammad; Qari, Alya; Balobaid, Ameera; Al-Sayed, Moeenaldeen

2017-06-01

Maple syrup urine disease (MSUD), an autosomal recessive inborn error of metabolism due to defects in the branched-chain α-ketoacid dehydrogenase (BCKD) complex, is commonly observed among other inherited metabolic disorders in the kingdom of Saudi Arabia. This report presents the results of mutation analysis of three of the four genes encoding the BCKD complex in 52 biochemically diagnosed MSUD patients originating from Saudi Arabia. The 25 mutations (20 novel) detected spanned across the entire coding regions of the BCKHDA , BCKDHB and DBT genes. There were no mutations found in the DLD gene in this cohort of patients. Prediction effects, conservation and modelling of novel mutations demonstrated that all were predicted to be disease-causing. All mutations presented in a homozygous form and we did not detect the presence of a "founder" mutation in any of three genes. In addition, prenatal molecular genetic testing was successfully carried out on chorionic villus samples or amniocenteses in 10 expectant mothers with affected children with MSUD, molecularly characterized by this study.

Differential expression of plasma miR-146a in sepsis patients compared with non-sepsis-SIRS patients.

PubMed

Wang, Lina; Wang, Hua-Cheng; Chen, Cha; Zeng, Jianming; Wang, Qian; Zheng, Lei; Yu, Huan-DU

2013-04-01

Sepsis is a subtype of systemic inflammatory response syndrome (SIRS), which is characterized by infection. Circulating microRNAs (miRNAs), including miR-150, miR-146a and miR-223, are potential biomarkers of sepsis. In this study, we demonstrated that measuring the relative expression of miR-146a/U6 in plasma, using the 2 -ΔΔCt method, provides a method for differentiating between sepsis and non-sepsis-SIRS. We observed a significant increase in miR-146a expression in the initial cohort of 6 non-sepsis-SIRS patients compared to the 4 sepsis patients (P=0.01) and in the second cohort of 8 non-sepsis-SIRS patients compared to the 10 sepsis patients (P=0.027). Additionally, we identified that sodium citrate and ethylenediaminetetraacetic acid (EDTA) K 2 may be used as anticoagulant reagents. Generation of a standard curve is not necessary in these diagnostic tests, unless the standard of normalization is carefully selected. Thus we provide more detailed guidance for the clinical use of circulating miRNA biomarkers.

Iatrogenic radiation exposure to patients with early onset spine and chest wall deformities.

PubMed

Khorsand, Derek; Song, Kit M; Swanson, Jonathan; Alessio, Adam; Redding, Gregory; Waldhausen, John

2013-08-01

Retrospective cohort series. Characterize average iatrogenic radiation dose to a cohort of children with thoracic insufficiency syndrome (TIS) during assessment and treatment at a single center with vertically expandable prosthetic titanium rib. Children with TIS undergo extensive evaluations to characterize their deformity. No standardized radiographical evaluation exists, but all reports use extensive imaging. The source and level of radiation these patients receive is not currently known. We evaluated a retrospective consecutive cohort of 62 children who had surgical treatment of TIS at our center from 2001-2011. Typical care included obtaining serial radiographs, spine and chest computed tomographic (CT) scans, ventilation/perfusion scans, and magnetic resonance images. Epochs of treatment were divided into time of initial evaluation to the end of initial vertically expandable prosthetic titanium rib implantation with each subsequent epoch delineated by the next surgical intervention. The effective dose for each examination was estimated within millisieverts (mSv). Plain radiographs were calculated from references. Effective dose was directly estimated for CT scans since 2007 and an average of effective dose from 2007-2011 was used for scans before 2007. Effective dose from fluoroscopy was directly estimated. All doses were reported in mSv. A cohort of 62 children had a total of 447 procedures. There were a total of 290 CT scans, 4293 radiographs, 147 magnetic resonance images, and 134 ventilation/perfusion scans. The average accumulated effective dose was 59.6 mSv for children who had completed all treatment, 13.0 mSv up to initial surgery, and 3.2 mSv for each subsequent epoch of treatment. CT scans accounted for 74% of total radiation dose. Children managed for TIS using a consistent protocol received iatrogenic radiation doses that were on average 4 times the estimated average US background radiation exposure of 3 mSv/yr. CT scans comprised 74% of the total dose. 3.

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

Increased subsequent risk of inflammatory bowel disease association in patients with chronic pancreatitis: a nationwide population-based cohort study.

PubMed

Chen, Yu-Long; Hsu, Chin-Wang; Cheng, Cheng-Chung; Yiang, Giou-Teng; Lin, Chin-Sheng; Lin, Cheng-Li; Sung, Fung-Chang; Liang, Ji-An

2017-06-01

To investigate the relationship between chronic pancreatitis (CP) and inflammatory bowel disease (IBD) in a large population-based cohort study. Data was obtained from the Taiwan National Health Insurance Research Database. The cohort study comprised 17,796 patients newly diagnosed with CP between 2000 and 2010 and 71,164 matched controls. A Cox proportional hazards model was used for evaluating the risk of IBD in the CP and comparison cohorts. When examined with a mean follow-up period of 4.87 and 6.04 years for the CP and comparison cohorts, respectively, the overall incidence of IBD was 10.3 times higher in the CP cohort than in the comparison cohort (5.75 vs. 0.56 per 10,000 person-years). Compared with the comparison cohort, the CP cohort exhibited a higher risk of IBD, irrespective of age, sex, and presence or absence of comorbidities. Moreover, the CP cohort was associated with a significantly higher risk of Crohn's disease (adjusted hazard ratio [aHR] = 12.9, 95% confidence interval [CI] = 5.15-32.5) and ulcerative colitis (aHR = 2.80, 95% CI = 1.00-7.86). This nationwide population-based cohort study revealed a significantly higher risk of IBD in patients with CP compared with control group. Clinicians should notice this association to avoid delayed diagnosis of IBD in patients with CP.

The pathophysiology of chronic noncommunicating hydrocephalus: lessons from continuous intracranial pressure monitoring and ventricular infusion testing.

PubMed

Eide, Per Kristian

2017-08-11

OBJECTIVE The pathophysiology of chronic noncommunicating hydrocephalus (ncHC) is poorly understood. This present study explored whether lessons about the pathophysiology of this clinical entity might be retrieved from results of overnight monitoring of pulsatile and static intracranial pressure (ICP) and ventricular infusion testing. METHODS The study cohort included adult patients (> 20 years of age) with chronic ncHC due to aqueductal stenosis in whom symptoms had lasted a minimum of 6 months. A reference cohort consisted of age- and sex-matched patients managed for communicating HC (cHC). Information about symptoms and clinical improvement following surgery was retrieved from a quality register, and results of overnight ICP recordings and ventricular infusion testing were retrieved from the hospital ICP database. RESULTS The cohort with ncHC consisted of 61 patients of whom 6 (10%) were managed conservatively, 34 (56%) by endoscopic third ventriculostomy (ETV), and 21 (34%) using ETV and subsequent shunt surgery. In patients responding to surgery, pulsatile ICP (mean ICP wave amplitude) was significantly increased to a similar magnitude in patients with ncHC and the reference cohort (cHC). Furthermore, intracranial compliance (ICC) was reduced in clinical responders. The results of ventricular infusion testing provided evidence that patients responding to ETV have impaired ventricular CSF absorption, while those requiring shunt placement after ETV present with impaired CSF absorption both in the intraventricular and extraventricular compartments. CONCLUSIONS The study may provide some lessons about the pathophysiology of chronic ncHC. First, increased pulsatile ICP and impaired ICC characterize patients with chronic ncHC who respond clinically to CSF diversion surgery, even though static ICP is not increased. Second, in patients responding clinically to ETV, impaired ventricular CSF absorption may be a key factor. Patients requiring shunt placement for clinical response appear to have both intraventricular and extraventricular CSF absorption failure. A subgroup of patients with ncHC due to aqueductal stenosis has normal ventricular CSF absorption and normal ICC and may not be in need of surgical CSF diversion.

The gut mycobiome of the Human Microbiome Project healthy cohort.

PubMed

Nash, Andrea K; Auchtung, Thomas A; Wong, Matthew C; Smith, Daniel P; Gesell, Jonathan R; Ross, Matthew C; Stewart, Christopher J; Metcalf, Ginger A; Muzny, Donna M; Gibbs, Richard A; Ajami, Nadim J; Petrosino, Joseph F

2017-11-25

Most studies describing the human gut microbiome in healthy and diseased states have emphasized the bacterial component, but the fungal microbiome (i.e., the mycobiome) is beginning to gain recognition as a fundamental part of our microbiome. To date, human gut mycobiome studies have primarily been disease centric or in small cohorts of healthy individuals. To contribute to existing knowledge of the human mycobiome, we investigated the gut mycobiome of the Human Microbiome Project (HMP) cohort by sequencing the Internal Transcribed Spacer 2 (ITS2) region as well as the 18S rRNA gene. Three hundred seventeen HMP stool samples were analyzed by ITS2 sequencing. Fecal fungal diversity was significantly lower in comparison to bacterial diversity. Yeast dominated the samples, comprising eight of the top 15 most abundant genera. Specifically, fungal communities were characterized by a high prevalence of Saccharomyces, Malassezia, and Candida, with S. cerevisiae, M. restricta, and C. albicans operational taxonomic units (OTUs) present in 96.8, 88.3, and 80.8% of samples, respectively. There was a high degree of inter- and intra-volunteer variability in fungal communities. However, S. cerevisiae, M. restricta, and C. albicans OTUs were found in 92.2, 78.3, and 63.6% of volunteers, respectively, in all samples donated over an approximately 1-year period. Metagenomic and 18S rRNA gene sequencing data agreed with ITS2 results; however, ITS2 sequencing provided greater resolution of the relatively low abundance mycobiome constituents. Compared to bacterial communities, the human gut mycobiome is low in diversity and dominated by yeast including Saccharomyces, Malassezia, and Candida. Both inter- and intra-volunteer variability in the HMP cohort were high, revealing that unlike bacterial communities, an individual's mycobiome is no more similar to itself over time than to another person's. Nonetheless, several fungal species persisted across a majority of samples, evidence that a core gut mycobiome may exist. ITS2 sequencing data provided greater resolution of the mycobiome membership compared to metagenomic and 18S rRNA gene sequencing data, suggesting that it is a more sensitive method for studying the mycobiome of stool samples.

Kidney stones and cardiovascular risk: a meta-analysis of cohort studies.

PubMed

Liu, Yanqiong; Li, Shan; Zeng, Zhiyu; Wang, Jian; Xie, Li; Li, Taijie; He, Yu; Qin, Xue; Zhao, Jinmin

2014-09-01

Recent epidemiologic evidence suggests an association between kidney stones and incident cardiovascular disease after adjusting for other cardiovascular risk factors, but results are inconsistent. Meta-analysis of cohort studies. Patients with kidney stones. Cohort studies with data for kidney stones and cardiovascular morbidity identified in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and conference proceedings through February 27, 2014. Kidney stones as determined by physician diagnosis, clinical coding, or self-reported scales. Cardiovascular disease, coronary heart disease (CHD), and stroke. 6 cohort studies that contained 49,597 patients with kidney stones and 3,558,053 controls, with 133,589 cardiovascular events, were included. Pooled results suggested that kidney stones were associated with an increased adjusted risk estimate for CHD (HR, 1.19; 95% CI, 1.05-1.35; P=0.05; n=6 cohorts) and stroke (HR, 1.40; 95% CI, 1.20-1.64; P<0.001; n=3 cohorts). In particular, kidney stones conferred HRs of 1.29 (95% CI, 1.10-1.52; n=6 cohorts) and 1.31 (95% CI, 1.05-1.65; n=4 cohorts) for myocardial infarction and coronary revascularization, respectively. Moreover, the pooled female cohorts showed a statistically significant association (HR, 1.49; 95% CI, 1.21-1.82; n=4 cohorts), whereas the male cohorts showed no association (HR, 1.15; 95% CI, 0.89-1.50; n=2 cohorts). Results may be limited by substantial heterogeneity, likelihood of residual confounding, and paucity of studies that separately evaluated for effect modification by sex. Kidney stones were associated with increased cardiovascular risk, including the risk for incident CHD or stroke. There is some suggestion that the risk may be higher in women than men. Further prospective studies are needed to determine whether the association is sex specific. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Selective reporting bias of harm outcomes within studies: findings from a cohort of systematic reviews.

PubMed

Saini, Pooja; Loke, Yoon K; Gamble, Carrol; Altman, Douglas G; Williamson, Paula R; Kirkham, Jamie J

2014-11-21

To determine the extent and nature of selective non-reporting of harm outcomes in clinical studies that were eligible for inclusion in a cohort of systematic reviews. Cohort study of systematic reviews from two databases. Outcome reporting bias in trials for harm outcomes (ORBIT II) in systematic reviews from the Cochrane Library and a separate cohort of systematic reviews of adverse events. 92 systematic reviews of randomised controlled trials and non-randomised studies published in the Cochrane Library between issue 9, 2012 and issue 2, 2013 (Cochrane cohort) and 230 systematic reviews published between 1 January 2007 and 31 December 2011 in other publications, synthesising data on harm outcomes (adverse event cohort). A 13 point classification system for missing outcome data on harm was developed and applied to the studies. 86% (79/92) of reviews in the Cochrane cohort did not include full data from the main harm outcome of interest of each review for all of the eligible studies included within that review; 76% (173/230) for the adverse event cohort. Overall, the single primary harm outcome was inadequately reported in 76% (705/931) of the studies included in the 92 reviews from the Cochrane cohort and not reported in 47% (4159/8837) of the 230 reviews in the adverse event cohort. In a sample of primary studies not reporting on the single primary harm outcome in the review, scrutiny of the study publication revealed that outcome reporting bias was suspected in nearly two thirds (63%, 248/393). The number of reviews suspected of outcome reporting bias as a result of missing or partially reported harm related outcomes from at least one eligible study is high. The declaration of important harms and the quality of the reporting of harm outcomes must be improved in both primary studies and systematic reviews. © Saini et al 2014.

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.

Array-CGH Analysis in a Cohort of Phenotypically Well-Characterized Individuals with "Essential" Autism Spectrum Disorders

ERIC Educational Resources Information Center

Napoli, Eleonora; Russo, Serena; Casula, Laura; Alesi, Viola; Amendola, Filomena Alessandra; Angioni, Adriano; Novelli, Antonio; Valeri, Giovanni; Menghini, Deny; Vicari, Stefano

2018-01-01

Copy-number variants (CNVs) are associated with susceptibility to autism spectrum disorder (ASD). To detect the presence of CNVs, we conducted an array-comparative genomic hybridization (array-CGH) analysis in 133 children with "essential" ASD phenotype. Genetic analyses documented that 12 children had causative CNVs (C-CNVs), 29…

Psychiatric Disorders and Intellectual Functioning throughout Development in Velocardiofacial (22q11.2 Deletion) Syndrome

ERIC Educational Resources Information Center

Green, Tamar; Gothelf, Doron; Glaser, Bronwyn; Debbane, Martin; Frisch, Amos; Kotler, Moshe; Weizman, Abraham; Eliez, Stephan

2009-01-01

Objective: Velocardiofacial syndrome (VCFS) is associated with cognitive deficits and high rates of schizophrenia and other neuropsychiatric disorders. We report the data from two large cohorts of individuals with VCFS from Israel and Western Europe to characterize the neuropsychiatric phenotype from childhood to adulthood in a large sample.…

European Prevention of Alzheimer's Dementia Registry: Recruitment and prescreening approach for a longitudinal cohort and prevention trials.

PubMed

Vermunt, Lisa; Veal, Colin D; Ter Meulen, Lea; Chrysostomou, Charalambos; van der Flier, Wiesje; Frisoni, Giovanni B; Guessous, Idris; Kivipelto, Miia; Marizzoni, Moira; Martinez-Lage, Pablo; Molinuevo, José Luis; Porteous, David; Ritchie, Karen; Scheltens, Philip; Ousset, Pierre-Jean; Ritchie, Craig W; Luscan, Gerald; Brookes, Anthony J; Visser, Pieter Jelle

2018-06-01

It is a challenge to find participants for Alzheimer's disease (AD) prevention trials within a short period of time. The European Prevention of Alzheimer's Dementia Registry (EPAD) aims to facilitate recruitment by preselecting subjects from ongoing cohort studies. This article introduces this novel approach. A virtual registry, with access to risk factors and biomarkers for AD through minimal data sets of ongoing cohort studies, was set up. To date, ten cohorts have been included in the EPAD. Around 2500 participants have been selected, using variables associated with the risk for AD. Of these, 15% were already recruited in the EPAD longitudinal cohort study, which serves as a trial readiness cohort. This study demonstrates that a virtual registry can be used for the preselection of participants for AD studies. Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Precision Medicine Approaches to Diabetic Kidney Disease: Tissue as an Issue.

PubMed

Gluck, Caroline; Ko, Yi-An; Susztak, Katalin

2017-05-01

Precision medicine approaches, that tailor medications to specific individuals has made paradigm-shifting improvements for patients with certain cancer types. Such approaches, however, have not been implemented for patients with diabetic kidney disease. Precision medicine could offer new avenues for novel diagnostic, prognostic and targeted therapeutics development. Genetic studies associated with multiscalar omics datasets from tissue and cell types of interest of well-characterized cohorts are needed to change the current paradigm. In this review, we will discuss precision medicine approaches that the nephrology community can take to analyze tissue samples to develop new therapeutics for patients with diabetic kidney disease.

Time-location patterns of a diverse population of older adults: the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

PubMed

Spalt, Elizabeth W; Curl, Cynthia L; Allen, Ryan W; Cohen, Martin; Adar, Sara D; Stukovsky, Karen H; Avol, Ed; Castro-Diehl, Cecilia; Nunn, Cathy; Mancera-Cuevas, Karen; Kaufman, Joel D

2016-06-01

The primary aim of this analysis was to present and describe questionnaire data characterizing time-location patterns of an older, multiethnic population from six American cities. We evaluated the consistency of results from repeated administration of this questionnaire and between this questionnaire and other questionnaires collected from participants of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). Participants reported spending most of their time inside their homes (average: 121 h/week or 72%). More than 50% of the participants reported spending no time in several of the location options, including at home outdoors, at work/volunteer/school locations indoors or outdoors, or in "other" locations outdoors. We observed consistency between self-reported time-location patterns from repeated administration of the time-location questionnaire and compared with other survey instruments. Comparisons with national cohorts demonstrated the differences in time-location patterns in the MESA Air cohort due to differences in demographics, but the data showed similar trends in patterns by age, gender, season, and employment status. This study was the first to explicitly examine the time-location patterns in an older, multiethnic population and the first to add data on Chinese participants. These data can be used to inform future epidemiological research of MESA Air and other studies that include diverse populations.

Differences in the Association between Serum Leptin Levels and Body Mass Index in Black and White Women: A Report from the Southern Community Cohort Study

PubMed Central

Cohen, Sarah S.; Fowke, Jay H.; Cai, Qiuyin; Buchowski, Maciej S.; Signorello, Lisa B.; Hargreaves, Margaret K.; Zheng, Wei; Blot, William J.; Matthews, Charles E.

2012-01-01

Background/Aims Leptin may be an important link between obesity and many high-burden diseases, including cancer and cardiovascular disease, but leptin levels and correlates in individuals of diverse racial backgrounds have not been well characterized despite racial differences in incidence and mortality patterns for many obesity-related diseases. Methods In a cross-sectional study of 915 white and 892 black women enrolled in the Southern Community Cohort Study (age 40–79 years, half postmenopausal), serum leptin levels were compared between the race groups and across categories of body mass index (BMI). Potential correlates of leptin were assessed via race-stratified linear regression models. Results Blacks had higher unadjusted leptin levels than whites (geometric mean 22.4 vs. 19.0 ng/ml; p < 0.0001). Leptin increased with increasing BMI, and racial differences in leptin were most pronounced in women with BMI ≥25. Significant correlates of leptin included BMI, age, alcohol consumption, cigarette smoking, diabetes (both races) and fat consumption (black women only). Leptin remained higher in black women (22.7 vs. 18.8 ng/ml) after adjustment for these factors. Conclusions Persistent racial differences in leptin concentrations exist after adjustment for BMI and other factors. Leptin assessment may be informative in future studies that investigate racial differences in the development of obesity-related diseases. PMID:22353927

Returning findings within longitudinal cohort studies: the 1958 birth cohort as an exemplar.

PubMed

Wallace, Susan E; Walker, Neil M; Elliott, Jane

2014-01-01

Population-based, prospective longitudinal cohort studies are considering the issues surrounding returning findings to individuals as a result of genomic and other medical research studies. While guidance is being developed for clinical settings, the process is less clear for those conducting longitudinal research. This paper discusses work conducted on behalf of The UK Cohort and Longitudinal Study Enhancement Resource programme (CLOSER) to examine consent requirements, process considerations and specific examples of potential findings in the context of the 1958 British Birth cohort. Beyond deciding which findings to return, there are questions of whether re-consent is needed and the possible impact on the study, how the feedback process will be managed, and what resources are needed to support that process. Recommendations are made for actions a cohort study should consider taking when making vital decisions regarding returning findings. Any decisions need to be context-specific, arrived at transparently, communicated clearly, and in the best interests of both the participants and the study.

Cohort Differences in Cognitive Aging in the Longitudinal Aging Study Amsterdam.

PubMed

Brailean, Anamaria; Huisman, Martijn; Prince, Martin; Prina, A Matthew; Deeg, Dorly J H; Comijs, Hannie

2016-09-30

This study aims to examine cohort differences in cognitive performance and rates of change in episodic memory, processing speed, inductive reasoning, and general cognitive performance and to investigate whether these cohort effects may be accounted for by education attainment. The first cohort (N = 705) was born between 1920 and 1930, whereas the second cohort (N = 646) was born between 1931 and 1941. Both birth cohorts were aged 65 to 75 years at baseline and were followed up 3 and 6 years later. Data were analyzed using linear mixed models. The later born cohort had better general cognitive performance, inductive reasoning, and processing speed at baseline, but cohort differences in inductive reasoning and general cognitive performance disappeared after adjusting for education. The later born cohort showed steeper decline in processing speed. Memory decline was steeper in the earlier born cohort but only from Time 1 to Time 3 when the same memory test was administered. Education did not account for cohort differences in cognitive decline. The later born cohort showed better initial performance in certain cognitive abilities, but no better preservation of cognitive abilities overtime compared with the earlier born cohort. These findings carry implications for healthy cognitive aging. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America.

European Birth Cohorts for Environmental Health Research

PubMed Central

Casas, Maribel; Bergström, Anna; Carmichael, Amanda; Cordier, Sylvaine; Eggesbø, Merete; Eller, Esben; Fantini, Maria P.; Fernández, Mariana F.; Fernández-Somoano, Ana; Gehring, Ulrike; Grazuleviciene, Regina; Hohmann, Cynthia; Karvonen, Anne M.; Keil, Thomas; Kogevinas, Manolis; Koppen, Gudrun; Krämer, Ursula; Kuehni, Claudia E.; Magnus, Per; Majewska, Renata; Andersen, Anne-Marie Nybo; Patelarou, Evridiki; Petersen, Maria Skaalum; Pierik, Frank H.; Polanska, Kinga; Porta, Daniela; Richiardi, Lorenzo; Santos, Ana Cristina; Slama, Rémy; Sram, Radim J.; Thijs, Carel; Tischer, Christina; Toft, Gunnar; Trnovec, Tomáš; Vandentorren, Stephanie; Vrijkotte, Tanja G.M.; Wilhelm, Michael; Wright, John; Nieuwenhuijsen, Mark

2011-01-01

Background: Many pregnancy and birth cohort studies investigate the health effects of early-life environmental contaminant exposure. An overview of existing studies and their data is needed to improve collaboration, harmonization, and future project planning. Objectives: Our goal was to create a comprehensive overview of European birth cohorts with environmental exposure data. Methods: Birth cohort studies were included if they a) collected data on at least one environmental exposure, b) started enrollment during pregnancy or at birth, c) included at least one follow-up point after birth, d) included at least 200 mother–child pairs, and e) were based in a European country. A questionnaire collected information on basic protocol details and exposure and health outcome assessments, including specific contaminants, methods and samples, timing, and number of subjects. A full inventory can be searched on www.birthcohortsenrieco.net. Results: Questionnaires were completed by 37 cohort studies of > 350,000 mother–child pairs in 19 European countries. Only three cohorts did not participate. All cohorts collected biological specimens of children or parents. Many cohorts collected information on passive smoking (n = 36), maternal occupation (n = 33), outdoor air pollution (n = 27), and allergens/biological organisms (n = 27). Fewer cohorts (n = 12–19) collected information on water contamination, ionizing or nonionizing radiation exposures, noise, metals, persistent organic pollutants, or other pollutants. All cohorts have information on birth outcomes; nearly all on asthma, allergies, childhood growth and obesity; and 26 collected information on child neurodevelopment. Conclusion: Combining forces in this field will yield more efficient and conclusive studies and ultimately improve causal inference. This impressive resource of existing birth cohort data could form the basis for longer-term and worldwide coordination of research on environment and child health. PMID:21878421

Pediatric severe sepsis in U.S. children's hospitals.

PubMed

Balamuth, Fran; Weiss, Scott L; Neuman, Mark I; Scott, Halden; Brady, Patrick W; Paul, Raina; Farris, Reid W D; McClead, Richard; Hayes, Katie; Gaieski, David; Hall, Matt; Shah, Samir S; Alpern, Elizabeth R

2014-11-01

To compare the prevalence, resource utilization, and mortality for pediatric severe sepsis identified using two established identification strategies. Observational cohort study from 2004 to 2012. Forty-four pediatric hospitals contributing data to the Pediatric Health Information Systems database. Children 18 years old or younger. We identified patients with severe sepsis or septic shock by using two International Classification of Diseases, 9th edition, Clinical Modification-based coding strategies: 1) combinations of International Classification of Diseases, 9th edition, Clinical Modification codes for infection plus organ dysfunction (combination code cohort); 2) International Classification of Diseases, 9th edition, Clinical Modification codes for severe sepsis and septic shock (sepsis code cohort). Outcomes included prevalence of severe sepsis, as well as hospital and ICU length of stay, and mortality. Outcomes were compared between the two cohorts examining aggregate differences over the study period and trends over time. The combination code cohort identified 176,124 hospitalizations (3.1% of all hospitalizations), whereas the sepsis code cohort identified 25,236 hospitalizations (0.45%), a seven-fold difference. Between 2004 and 2012, the prevalence of sepsis increased from 3.7% to 4.4% using the combination code cohort and from 0.4% to 0.7% using the sepsis code cohort (p < 0.001 for trend in each cohort). Length of stay (hospital and ICU) and costs decreased in both cohorts over the study period (p < 0.001). Overall, hospital mortality was higher in the sepsis code cohort than the combination code cohort (21.2% [95% CI, 20.7-21.8] vs 8.2% [95% CI, 8.0-8.3]). Over the 9-year study period, there was an absolute reduction in mortality of 10.9% (p < 0.001) in the sepsis code cohort and 3.8% (p < 0.001) in the combination code cohort. Prevalence of pediatric severe sepsis increased in the studied U.S. children's hospitals over the past 9 years, whereas resource utilization and mortality decreased. Epidemiologic estimates of pediatric severe sepsis varied up to seven-fold depending on the strategy used for case ascertainment.

Pediatric Severe Sepsis in US Children’s Hospitals

PubMed Central

Balamuth, Fran; Weiss, Scott L.; Neuman, Mark I.; Scott, Halden; Brady, Patrick W.; Paul, Raina; Farris, Reid W.D.; McClead, Richard; Hayes, Katie; Gaieski, David; Hall, Matt; Shah, Samir S.; Alpern, Elizabeth R.

2014-01-01

Objective To compare the prevalence, resource utilization, and mortality for pediatric severe sepsis identified using two established identification strategies. Design Observational cohort study from 2004–2012. Setting Forty-four pediatric hospitals contributing data to the Pediatric Health Information Systems database. Patients Children ≤18 years of age. Measurements and Main Results We identified patients with severe sepsis or septic shock by using two International Classification of Diseases, 9th edition-Clinical Modification (ICD9-CM) based coding strategies: 1) combinations of ICD9-CM codes for infection plus organ dysfunction (combination code cohort); 2) ICD9-CM codes for severe sepsis and septic shock (sepsis code cohort). Outcomes included prevalence of severe sepsis, as well as hospital and intensive care unit (ICU) length of stay (LOS), and mortality. Outcomes were compared between the two cohorts examining aggregate differences over the study period and trends over time. The combination code cohort identified, 176,124 hospitalizations (3.1% of all hospitalizations), while the sepsis code cohort identified 25,236 hospitalizations (0.45%), a 7-fold difference. Between 2004 and 2012, the prevalence of sepsis increased from 3.7% to 4.4% using the combination code cohort and from 0.4% to 0.7% using the sepsis code cohort (p<0.001 for trend in each cohort). LOS (hospital and ICU) and costs decreased in both cohorts over the study period (p<0.001). Overall hospital mortality was higher in the sepsis code cohort than the combination code cohort (21.2%, (95% CI: 20.7–21.8 vs. 8.2%,(95% CI: 8.0–8.3). Over the 9 year study period, there was an absolute reduction in mortality of 10.9% (p<0.001) in the sepsis code cohort and 3.8% (p<0.001) in the combination code cohort. Conclusions Prevalence of pediatric severe sepsis increased in the studied US children’s hospitals over the past 9 years, though resource utilization and mortality decreased. Epidemiologic estimates of pediatric severe sepsis varied up to 7-fold depending on the strategy used for case ascertainment. PMID:25162514

Disability Rises Gradually for a Cohort of Older Americans

PubMed Central

Brown, Dustin C.; Zajacova, Anna

2017-01-01

Objectives: We study changes in average disability over nearly two decades for a large epidemiological cohort of older Americans. As some people exit by mortality, do average disability levels for the living cohort rise rapidly, rise gradually, stay steady, or decline? Method: Data are from the Study of Asset and Health Dynamics Among the Oldest Old (AHEAD) cohort for 1993–2010. Cohort members are aged 70+ in 1993 (mean = 77.5 years), and the survivors are aged 87+ in 2010 (mean = 90.2 years). Personal care disability (activities of daily living), household management disability (instrumental activities of daily living), and physical limitations are studied. We study average disability for the living cohort over time and the disability histories for decedent and survivor groups. Results: Average disability rises gradually over time for the living cohort. Earlier decedent groups have higher average disability than later ones. Near death, disability rises sharply for all decedent groups. Longer surviving groups have less average disability, and slower disability increases, than shorter surviving groups. All results are repeated for younger cohort members (baseline age = 70–79 years), older ones (baseline age = 80+ years), women, and men. Discussion: As a cohort ages, average disability among living members increases gradually, signaling behavioral, psychological, and biological fitness in very old persons. PMID:26968638

Toward standardized reporting for a cohort study on functioning: The Swiss Spinal Cord Injury Cohort Study.

PubMed

Prodinger, Birgit; Ballert, Carolina S; Brach, Mirjam; Brinkhof, Martin W G; Cieza, Alarcos; Hug, Kerstin; Jordan, Xavier; Post, Marcel W M; Scheel-Sailer, Anke; Schubert, Martin; Tennant, Alan; Stucki, Gerold

2016-02-01

Functioning is an important outcome to measure in cohort studies. Clear and operational outcomes are needed to judge the quality of a cohort study. This paper outlines guiding principles for reporting functioning in cohort studies and addresses some outstanding issues. Principles of how to standardize reporting of data from a cohort study on functioning, by deriving scores that are most useful for further statistical analysis and reporting, are outlined. The Swiss Spinal Cord Injury Cohort Study Community Survey serves as a case in point to provide a practical application of these principles. Development of reporting scores must be conceptually coherent and metrically sound. The International Classification of Functioning, Disability and Health (ICF) can serve as the frame of reference for this, with its categories serving as reference units for reporting. To derive a score for further statistical analysis and reporting, items measuring a single latent trait must be invariant across groups. The Rasch measurement model is well suited to test these assumptions. Our approach is a valuable guide for researchers and clinicians, as it fosters comparability of data, strengthens the comprehensiveness of scope, and provides invariant, interval-scaled data for further statistical analyses of functioning.

[18F]FDDNP PET in Tauopathies: Correlation to post mortem Pathology in a Case of Progressive Supranuclear Palsy (PSP)

NASA Astrophysics Data System (ADS)

Villegas, Brendon Josef

This investigation of [18F]FDDNP was conducted in an effort to confirm the presence of disease in a patient with Progressive Supranuclear Palsy (PSP) and to correlate the ante mortem PET scan results to the post mortem pathology. The immunohistochemical and immunofluorescent staining of Paired Helical Filamentous (PHF) tau (AT8) and Amyloid Beta (6F/3D) misfolded proteins demonstrated a widespread deposition in the cortical and subcortical nuclei, the white matter, cerebellar white matter and the medulla oblongata. The in vitro autoradiography demonstrated a neocortical signal comprised of well-delineated amyloid beta in the nucleated layers I/II and hyperphosphorylated tau in the deeper layers III through VI. The autoradiography was well correlated with the immunohistochemical staining in adjacent tissue slides. The binding of the parametric [ 18F]FDDNP distribution volume ratio (DVR) correlated well (Spearman's rho = 0.962, p = .004) with the deposition of tau but not with the presence of amyloid beta (Spearman's rho = -0.829, p = .041). The [ 18F]FDDNP DVR signal appears to be primarily due to the large amount of bound hyperphosphorylated tau (p-tau) and the amyloid beta negligibly contributes to the total signal. Unlabeled FDDNP was shown to bind to tau in the form of globose tangles in the rostral ventromedial medulla as confirmed with both Thioflavin S and PHF-tau Immunofluorescence. The binding of [18F]FDDNP to the human neuroanatomy was investigated in two cohorts of distinct tauopathies and compared to the binding in two tau-negative cohorts against control patients. A cohort of PSP patients (n = 12) with a mean age of 63.8 years and a cohort of Chronic Traumatic Encephalopathy (CTE) patients (n = 14) with a mean age of 58.1 years are both characterized by the presence of various degrees of tau pathology in their brains. The cohort of Parkinson's Disease (PD) patients (n = 16) with a mean age of 63.2 years is initially characterized by clinical symptoms similar to PSP [18F]FDDNP is able to differentiate between PD and PSP with statistical significance (p < .05) in the striatum; particularly within the caudate nucleus. The Huntington's Disease (HD) patients (n = 15) with a mean age of 36.8 years display motor degeneration from a loss of striatal medium spiny neurons with no presence of amyloid beta or p-tau. It has further been demonstrated with statistical certainty that CTE is discernible from control patients in the amygdala, the midbrain, the caudate nucleus and the anterior cingulate gyrus (p < .05). On the other hand, the HD and PD cohort were both found to have decreased binding of [18F]FDDNP binding in caudate nucleus when compared to all the control patients (p < .05). In the tauopathy cases studied, [18F]FDDNP has successfully demonstrated its differential capability to discriminate between PSP, CTE and PD. The [18F]FDDNP DVR signal in the cases of PSP and CTE closely correlated with hyperphosphorylated tau deposition, as confirmed by the post mortem autopsy of a case with PSP.

Students' perceptions of vertical and horizontal integration in a discipline-based dental school.

PubMed

Postma, T C; White, J G

2017-05-01

Integration is a key concern in discipline-based undergraduate dental curricula. Therefore, this study compared feedback on integration from students who participated in different instructional designs in a Comprehensive Patient Care course. The study was conducted at the University of Pretoria (2009-2011). Third-year cohorts (Cohorts A, B and C) participated in pre-clinical case-based learning, whilst fourth-year cohorts (Cohorts D and E) received didactic teaching in Comprehensive Patient Care. Cohorts A, D and E practised clinical Comprehensive Patient Care in a discipline-based clinic. Cohort B conducted their Comprehensive Patient Care patient examinations in a dedicated facility supervised by dedicated faculty responsible to teach integration. Students had to indicate on visual analogue scales whether the way they were taught at the school helped them to integrate knowledge from the same (horizontal integration) and preceding (vertical integration) year of study. The end-points of the scales were defined as 'definitely' and 'not at all'. Analysis of variance (ANOVA) was employed to measure the differences between cohorts according to the year of study. Third-year case-based learning cohorts rated the horizontal integration close to 80/100 and vertical integration ranging from 64 to 71/100. In year four, Cohort B rated vertical and horizontal integration 9-15% higher (ANOVA, P < 0.05) than Cohorts A and D. In year five, Cohort A rated vertical and horizontal integration 11-18% higher (ANOVA, P < 0.05) than Cohorts D and E. Pre-clinical case-based learning and Comprehensive Patient Care supervised by dedicated faculty were associated with more favourable perceptions about integration in the discipline-based undergraduate dental curriculum. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Serum 1,25-dihydroxyvitamin D and calcium intake affect rates of bone calcium deposition during pregnancy and the early postpartum period123

PubMed Central

O'Brien, Kimberly O; Donangelo, Carmen M; Ritchie, Lorrene D; Gildengorin, Ginny; Abrams, Steve

2012-01-01

Background: Factors affecting bone calcium deposition across pregnancy and lactation are not well characterized. Objective: The impact of maternal age, calcium intake, race-ethnicity, and vitamin D status on the rate of bone calcium deposition (VO+) was assessed across pregnancy and lactation. Design: Stable calcium isotopes were given to 46 women at pre- or early pregnancy (trimester 1), late pregnancy (trimester 3), and 3–10 wk postpartum. Three cohorts were included: 23 adolescents from Baltimore (MD), aged 16.5 ± 1.4 y (mean ± SD; Baltimore cohort); 13 adults from California, aged 29.5 ± 2.6 y (California cohort); and 10 adults from Brazil, aged 30.4 ± 4.0 y (Brazil cohort). The total exchangeable calcium pool, VO+, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D [1,25(OH)2D], parathyroid hormone, and calcium intake were evaluated. Results: At trimester 3, inverse associations between 1,25(OH)2D and VO+ were evident in the Baltimore (P = 0.059) and Brazil (P = 0.008) cohorts and in the whole group (P = 0.029); calcium intake was not a significant determinant of VO+ in any group during pregnancy. At postpartum, a significant positive association was evident between VO+ and calcium intake (P ≤ 0.002) and between VO+ and African ethnicity (P ≤ 0.004) in the whole group and within the Baltimore and Brazil cohorts. Conclusions: Elevated 1,25(OH)2D was associated with decreased rates of bone calcium deposition during late pregnancy, a finding that was particularly evident in pregnant adolescents and adult women with low calcium intakes. Higher dietary calcium intakes and African ethnicity were associated with elevated rates of bone calcium deposition in the postpartum period. PMID:22648718

Mysid Population Responses to Resource Limitation Differ from those Predicted by Cohort Studies

EPA Science Inventory

Effects of anthropogenic stressors on animal populations are often evaluated by assembling vital rate responses from isolated cohort studies into a single demographic model. However, models constructed from cohort studies are difficult to translate into ecological predictions be...

Preinjury Psychological Status, Injury Severity and Postdeployment Posttraumatic Stress Disorder

DTIC Science & Technology

2011-05-01

Millennium Cohort Study Team. Smallpox vaccination : comparison of self-reported and electronic vaccine records in the Millennium Cohort Study. Hum Vaccin ...Smith B, Leard CA, Smith TC, Reed RJ, Ryan MAK; Millennium Cohort Study Team. Anthrax vaccination in the Millennium Cohort: validation and measures of...in Adults With Autism Spectrum Dis- orders” by Suzuki et al, published in the March 2011 is- sue of the Archives (2011;68(3):306-313), some figure

Median regression spline modeling of longitudinal FEV1 measurements in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) patients.

PubMed

Conrad, Douglas J; Bailey, Barbara A; Hardie, Jon A; Bakke, Per S; Eagan, Tomas M L; Aarli, Bernt B

2017-01-01

Clinical phenotyping, therapeutic investigations as well as genomic, airway secretion metabolomic and metagenomic investigations can benefit from robust, nonlinear modeling of FEV1 in individual subjects. We demonstrate the utility of measuring FEV1 dynamics in representative cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) populations. Individual FEV1 data from CF and COPD subjects were modeled by estimating median regression splines and their predicted first and second derivatives. Classes were created from variables that capture the dynamics of these curves in both cohorts. Nine FEV1 dynamic variables were identified from the splines and their predicted derivatives in individuals with CF (n = 177) and COPD (n = 374). Three FEV1 dynamic classes (i.e. stable, intermediate and hypervariable) were generated and described using these variables from both cohorts. In the CF cohort, the FEV1 hypervariable class (HV) was associated with a clinically unstable, female-dominated phenotypes while stable FEV1 class (S) individuals were highly associated with the male-dominated milder clinical phenotype. In the COPD cohort, associations were found between the FEV1 dynamic classes, the COPD GOLD grades, with exacerbation frequency and symptoms. Nonlinear modeling of FEV1 with splines provides new insights and is useful in characterizing CF and COPD clinical phenotypes.

Characterizing functional lung heterogeneity in COPD using reference equations for CT scan-measured lobar volumes.

PubMed

Come, Carolyn E; Diaz, Alejandro A; Curran-Everett, Douglas; Muralidhar, Nivedita; Hersh, Craig P; Zach, Jordan A; Schroeder, Joyce; Lynch, David A; Celli, Bartolome; Washko, George R

2013-06-01

CT scanning is increasingly used to characterize COPD. Although it is possible to obtain CT scan-measured lung lobe volumes, normal ranges remain unknown. Using COPDGene data, we developed reference equations for lobar volumes at maximal inflation (total lung capacity [TLC]) and relaxed exhalation (approximating functional residual capacity [FRC]). Linear regression was used to develop race-specific (non-Hispanic white [NHW], African American) reference equations for lobar volumes. Covariates included height and sex. Models were developed in a derivation cohort of 469 subjects with normal pulmonary function and validated in 546 similar subjects. These cohorts were combined to produce final prediction equations, which were applied to 2,191 subjects with old GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage II to IV COPD. In the derivation cohort, women had smaller lobar volumes than men. Height positively correlated with lobar volumes. Adjusting for height, NHWs had larger total lung and lobar volumes at TLC than African Americans; at FRC, NHWs only had larger lower lobes. Age and weight had no effect on lobar volumes at TLC but had small effects at FRC. In subjects with COPD at TLC, upper lobes exceeded 100% of predicted values in GOLD II disease; lower lobes were only inflated to this degree in subjects with GOLD IV disease. At FRC, gas trapping was severe irrespective of disease severity and appeared uniform across the lobes. Reference equations for lobar volumes may be useful in assessing regional lung dysfunction and how it changes in response to pharmacologic therapies and surgical or endoscopic lung volume reduction.

Outdoor characterization of radio frequency electromagnetic fields in a Spanish birth cohort

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

Calvente, I.; Department of Radiology and Physical Medicine, School of Medicine, University of Granada, Av. Madreid s/n, Granada 18071; Fernández, M.F.

There is considerable public concern in many countries about the possible adverse effects of exposure to non-ionizing radiation electromagnetic fields, especially in vulnerable populations such as children. The aim of this study was to characterize environmental exposure profiles within the frequency range 100 kHz–6 GHz in the immediate surrounds of the dwellings of 123 families from the INMA-Granada birth cohort in Southern Spain, using spot measurements. The arithmetic mean root mean-square electric field (E{sub RMS}) and power density (S{sub RMS}) values were, respectively, 195.79 mV/m (42.3% of data were above this mean) and 799.01 µW/m{sup 2} (30% of values weremore » above this mean); median values were 148.80 mV/m and 285.94 µW/m{sup 2}, respectively. Exposure levels below the quantification limit were assigned a value of 0.01 V/m. Incident field strength levels varied widely among different areas or towns/villages, demonstrating spatial variability in the distribution of exposure values related to the surface area population size and also among seasons. Although recorded values were well below International Commission for Non-Ionizing Radiation Protection reference levels, there is a particular need to characterize incident field strength levels in vulnerable populations (e.g., children) because of their chronic and ever-increasing exposure. The effects of incident field strength have not been fully elucidated; however, it may be appropriate to apply the precautionary principle in order to reduce exposure in susceptible groups. - Highlights: • Spot measurements were performed in the immediate surrounds of children's dwellings. • Mean root mean-square electric field and power density values were calculated. • Most recorded values were far below international standard guideline limits. • Data demonstrate spatial variability in the distribution of exposure levels. • While adverse effects are proven, application of the precautionary principle may be appropriate.« less

Acupuncture decreased the risk of coronary heart disease in patients with fibromyalgia in Taiwan: a nationwide matched cohort study.

PubMed

Wu, Mei-Yao; Huang, Ming-Cheng; Chiang, Jen-Huai; Sun, Mao-Feng; Lee, Yu-Chen; Yen, Hung-Rong

2017-02-28

The aim of this study was to understand whether acupuncture can decrease the risk of coronary heart disease (CHD) in patients with fibromyalgia. Using data from the Taiwanese National Health Insurance Research Database, we performed a propensity score-matched cohort study to analyze patients with fibromyalgia diagnosed between 1 January 2000 and 31 December 2010. Patients who received acupuncture treatment, beginning with their initial date of fibromyalgia diagnosis and extending to 31 December 2010, were regarded as the acupuncture cohort. The no-acupuncture cohort comprised patients who never received acupuncture through 31 December 2010. A Cox regression model was used to adjust for age, sex, comorbidities, and drugs used. The HRs of the acupuncture and no-acupuncture cohorts were compared. After performing a 1:1 propensity score match, 58,899 patients in both cohorts were identified. Baseline characteristics were similar in both cohorts. The cumulative incidence of CHD was significantly lower in the acupuncture cohort (log-rank test, p < 0.001). In the follow-up period, 4389 patients in the acupuncture cohort (17.44 per 1000 person-years) and 8133 patients in the no-acupuncture cohort (38.36 per 1000 person-years) developed CHD (adjusted HR 0.43, 95% CI 0.41-0.45). The beneficial effect of acupuncture on the incidence of CHD was independent of age, sex, comorbidities, and statins used. Our study confirmed that acupuncture reduced the risk of CHD in patients with fibromyalgia in Taiwan. Further clinical and mechanistic studies are warranted.

Variance Function Regression in Hierarchical Age-Period-Cohort Models: Applications to the Study of Self-Reported Health

PubMed Central

Zheng, Hui; Yang, Yang; Land, Kenneth C.

2012-01-01

Two long-standing research problems of interest to sociologists are sources of variations in social inequalities and differential contributions of the temporal dimensions of age, time period, and cohort to variations in social phenomena. Recently, scholars have introduced a model called Variance Function Regression for the study of the former problem, and a model called Hierarchical Age-Period-Cohort regression has been developed for the study of the latter. This article presents an integration of these two models as a means to study the evolution of social inequalities along distinct temporal dimensions. We apply the integrated model to survey data on subjective health status. We find substantial age, period, and cohort effects, as well as gender differences, not only for the conditional mean of self-rated health (i.e., between-group disparities), but also for the variance in this mean (i.e., within-group disparities)—and it is detection of age, period, and cohort variations in the latter disparities that application of the integrated model permits. Net of effects of age and individual-level covariates, in recent decades, cohort differences in conditional means of self-rated health have been less important than period differences that cut across all cohorts. By contrast, cohort differences of variances in these conditional means have dominated period differences. In particular, post-baby boom birth cohorts show significant and increasing levels of within-group disparities. These findings illustrate how the integrated model provides a powerful framework through which to identify and study the evolution of variations in social inequalities across age, period, and cohort temporal dimensions. Accordingly, this model should be broadly applicable to the study of social inequality in many different substantive contexts. PMID:22904570

Feasibility of a cohort study on health risks caused by occupational exposure to radiofrequency electromagnetic fields

PubMed Central

2009-01-01

Background The aim of this study was to examine the feasibility of performing a cohort study on health risks from occupational exposure to radiofrequency electromagnetic fields (RF-EMF) in Germany. Methods A set of criteria was developed to evaluate the feasibility of such a cohort study. The criteria aimed at conditions of exposure and exposure assessment (level, duration, preferably on an individual basis), the possibility to assemble a cohort and the feasibility of ascertaining various disease endpoints. Results Twenty occupational settings with workers potentially exposed to RF-EMF and, in addition, a cohort of amateur radio operators were considered. Based on expert ratings, literature reviews and our set of predefined criteria, three of the cohorts were identified as promising for further evaluation: the personnel (technicians) of medium/short wave broadcasting stations, amateur radio operators, and workers on dielectric heat sealers. After further analyses, the cohort of workers on dielectric heat sealers seems not to be feasible due to the small number of exposed workers available and to the difficulty of assessing exposure (exposure depends heavily on the respective working process and mixture of exposures, e.g. plastic vapours), although exposure was highest in this occupational setting. The advantage of the cohort of amateur radio operators was the large number of persons it includes, while the advantage of the cohort of personnel working at broadcasting stations was the quality of retrospective exposure assessment. However, in the cohort of amateur radio operators the exposure assessment was limited, and the cohort of technicians was hampered by the small number of persons working in this profession. Conclusion The majority of occupational groups exposed to RF-EMF are not practicable for setting up an occupational cohort study due to the small numbers of exposed subjects or due to exposure levels being only marginally higher than those of the general public. PMID:19480652

Feasibility of Conducting a Longitudinal, Transnational Study of Filipino Migrants to the United States: A Dual-Cohort Design

PubMed Central

Gee, Gilbert C.; de Castro, A.B.; Wang, May C.; Crespi, Catherine M.; Morey, Brittany N.; Fujishiro, Kaori

2015-01-01

Most studies of immigrant health are cross-sectional and fail to collect information prior to migration, leading to potential bias and confounding. The present pilot study examines the feasibility of studying migrants prospectively, with baseline data collected before migration. The study followed two cohorts of Filipinos for one year, a migrant cohort (n=27) that emigrated to the U.S. and a second non-migrant cohort (n=26) in the Philippines. The one-year retention rate was 96% The migrant cohort arrived in the U.S. within 2 months of their baseline assessment. Migrants and non-migrants did not differ with regard to body mass index, waist circumference or waist to hip ratio at baseline or at follow-up. It is feasible to conduct a transnational, longitudinal study of two cohorts of Filipinos. This design provides important pre-migration information, is analogous to a natural experiment, can be upscaled, and allows for a rigorous examination of immigrant health. PMID:25913346

A prospective cohort study on ambient air pollution and respiratory morbidities including childhood asthma in adolescents from the western Cape Province: study protocol.

PubMed

Olaniyan, Toyib; Jeebhay, Mohamed; Röösli, Martin; Naidoo, Rajen; Baatjies, Roslynn; Künzil, Nino; Tsai, Ming; Davey, Mark; de Hoogh, Kees; Berman, Dilys; Parker, Bhawoodien; Leaner, Joy; Dalvie, Mohamed Aqiel

2017-09-16

There is evidence from existing literature that ambient air pollutant exposure in early childhood likely plays an important role in asthma exacerbation and other respiratory symptoms, with greater effect among asthmatic children. However, there is inconclusive evidence on the role of ambient air pollutant exposures in relation to increasing asthma prevalence as well as asthma induction in children. At the population level, little is known about the potential synergistic effects between pollen allergens and air pollutants since this type of association poses challenges in uncontrolled real life settings. In particular, data from sub-Sahara Africa is scarce and virtually absent among populations residing in informal residential settlements. A prospective cohort study of 600 school children residing in four informal settlement areas with varying potential ambient air pollutant exposure levels in the Western Cape in South Africa is carried-out. The study has two follow-up periods of at least six-months apart including an embedded panel study in summer and winter. The exposure assessment component models temporal and spatial variability of air quality in the four study areas over the study duration using land-use regression modelling (LUR). Additionally, daily pollen levels (mould spores, tree, grass and weed pollen) in the study areas are recorded. In the panel study asthma symptoms and serial peak flow measurements is recorded three times daily to determine short-term serial airway changes in relation to varying ambient air quality and pollen over 10-days during winter and summer. The health outcome component of the cohort study include; the presence of asthma using a standardised ISAAC questionnaire, spirometry, fractional exhaled nitric-oxide (FeNO) and the presence of atopy (Phadiatop). This research applies state of the art exposure assessment approaches to characterize the effects of ambient air pollutants on childhood respiratory health, with a specific focus on asthma and markers of airway inflammation (FeNO) in South African informal settlement areas by considering also pollen counts and meteorological factors. The study will generate crucial data on air pollution and asthma in low income settings in sub-Sahara Africa that is lacking in the international literature.

The Tohoku Medical Megabank Project: Design and Mission.

PubMed

Kuriyama, Shinichi; Yaegashi, Nobuo; Nagami, Fuji; Arai, Tomohiko; Kawaguchi, Yoshio; Osumi, Noriko; Sakaida, Masaki; Suzuki, Yoichi; Nakayama, Keiko; Hashizume, Hiroaki; Tamiya, Gen; Kawame, Hiroshi; Suzuki, Kichiya; Hozawa, Atsushi; Nakaya, Naoki; Kikuya, Masahiro; Metoki, Hirohito; Tsuji, Ichiro; Fuse, Nobuo; Kiyomoto, Hideyasu; Sugawara, Junichi; Tsuboi, Akito; Egawa, Shinichi; Ito, Kiyoshi; Chida, Koichi; Ishii, Tadashi; Tomita, Hiroaki; Taki, Yasuyuki; Minegishi, Naoko; Ishii, Naoto; Yasuda, Jun; Igarashi, Kazuhiko; Shimizu, Ritsuko; Nagasaki, Masao; Koshiba, Seizo; Kinoshita, Kengo; Ogishima, Soichi; Takai-Igarashi, Takako; Tominaga, Teiji; Tanabe, Osamu; Ohuchi, Noriaki; Shimosegawa, Toru; Kure, Shigeo; Tanaka, Hiroshi; Ito, Sadayoshi; Hitomi, Jiro; Tanno, Kozo; Nakamura, Motoyuki; Ogasawara, Kuniaki; Kobayashi, Seiichiro; Sakata, Kiyomi; Satoh, Mamoru; Shimizu, Atsushi; Sasaki, Makoto; Endo, Ryujin; Sobue, Kenji; Tohoku Medical Megabank Project Study Group, The; Yamamoto, Masayuki

2016-09-05

The Great East Japan Earthquake (GEJE) and resulting tsunami of March 11, 2011 gave rise to devastating damage on the Pacific coast of the Tohoku region. The Tohoku Medical Megabank Project (TMM), which is being conducted by Tohoku University Tohoku Medical Megabank Organization (ToMMo) and Iwate Medical University Iwate Tohoku Medical Megabank Organization (IMM), has been launched to realize creative reconstruction and to solve medical problems in the aftermath of this disaster. We started two prospective cohort studies in Miyagi and Iwate Prefectures: a population-based adult cohort study, the TMM Community-Based Cohort Study (TMM CommCohort Study), which will recruit 80 000 participants, and a birth and three-generation cohort study, the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study), which will recruit 70 000 participants, including fetuses and their parents, siblings, grandparents, and extended family members. The TMM CommCohort Study will recruit participants from 2013 to 2016 and follow them for at least 5 years. The TMM BirThree Cohort Study will recruit participants from 2013 to 2017 and follow them for at least 4 years. For children, the ToMMo Child Health Study, which adopted a cross-sectional design, was also started in November 2012 in Miyagi Prefecture. An integrated biobank will be constructed based on the two prospective cohort studies, and ToMMo and IMM will investigate the chronic medical impacts of the GEJE. The integrated biobank of TMM consists of health and clinical information, biospecimens, and genome and omics data. The biobank aims to establish a firm basis for personalized healthcare and medicine, mainly for diseases aggravated by the GEJE in the two prefectures. Biospecimens and related information in the biobank will be distributed to the research community. TMM itself will also undertake genomic and omics research. The aims of the genomic studies are: 1) to construct an integrated biobank; 2) to return genomic research results to the participants of the cohort studies, which will lead to the implementation of personalized healthcare and medicine in the affected areas in the near future; and 3) to contribute the development of personalized healthcare and medicine worldwide. Through the activities of TMM, we will clarify how to approach prolonged healthcare problems in areas damaged by large-scale disasters and how useful genomic information is for disease prevention.

Evolving perspectives on genetic discrimination in health insurance among health care providers.

PubMed

Huizenga, Carin R; Lowstuter, Katrina; Banks, Kimberly C; Lagos, Veronica I; Vandergon, Virginia O; Weitzel, Jeffrey N

2010-06-01

Previous studies have documented that concerns about genetic discrimination (GD) may influence access to and participation in medically necessary care. We sought to characterize how GD issues influence current cancer genetics professional (CGP) practice, determine if their attitudes regarding GD have changed over time, and compare their knowledge and attitudes regarding laws prohibiting GD to a contemporary cohort of non-genetics clinicians. Members of the National Society of Genetic Counselors Familial Cancer Special Interest Group were invited to complete a 39 item online survey, adapted from previously published instruments. The resulting data were compared to a survey of CGPs published in 2000 and to a contemporary cohort of non-genetics clinicians (n = 1,181). There were 153 qualified respondents. Compared to the historical CGP cohort (n = 163), a significantly greater proportion said they would bill insurance for the cost of genetic testing for themselves (P < 0.0001). Most CGPs (94%) considered the risk of GD to be low to theoretical, concordant with 64% who expressed confidence in existing federal laws prohibiting GD. The mean knowledge score of CGPs regarding GD protective laws was significantly greater than that of non-genetics clinicians (P < 0.001). As barometers of change, CGPs show a migration in opinion over the past 8 years, with decreased fear of GD and greater knowledge of laws prohibiting GD compared to non-genetics clinicians. Better knowledge of GD and protective legislation, may facilitate non-genetics clinician utilization of genetics and personalized medicine.

Genetic screening of Greek patients with Huntington’s disease phenocopies identifies an SCA8 expansion.

PubMed

Koutsis, G; Karadima, G; Pandraud, A; Sweeney, M G; Paudel, R; Houlden, H; Wood, N W; Panas, M

2012-09-01

Huntington’s disease (HD) is an autosomal dominant disorder characterized by a triad of chorea, psychiatric disturbance and cognitive decline. Around 1% of patients with HD-like symptoms lack the causative HD expansion and are considered HD phenocopies. Genetic diseases that can present as HD phenocopies include HD-like syndromes such as HDL1, HDL2 and HDL4 (SCA17), some spinocerebellar ataxias (SCAs) and dentatorubral-pallidoluysian atrophy (DRPLA). In this study we screened a cohort of 21 Greek patients with HD phenocopy syndromes formutations causing HDL2, SCA17, SCA1, SCA2, SCA3,SCA8, SCA12 and DRPLA. Fifteen patients (71%) had a positive family history. We identified one patient (4.8% of the total cohort) with an expansion of 81 combined CTA/CTG repeats at the SCA8 locus. This falls within what is believed to be the high-penetrance allele range. In addition to the classic HD triad, the patient had features of dystonia and oculomotor apraxia. There were no cases of HDL2, SCA17, SCA1, SCA2, SCA3, SCA12 or DRPLA. Given the controversy surrounding the SCA8 expansion, the present finding may be incidental. However, if pathogenic, it broadens the phenotype that may be associated with SCA8 expansions. The absence of any other mutations in our cohort is not surprising, given the low probability of reaching a genetic diagnosis in HD phenocopy patients.

New Onset Autoimmune Hepatitis during Anti-Tumor Necrosis Factor-Alpha Treatment in Children.

PubMed

Ricciuto, Amanda; Kamath, Binita M; Walters, Thomas D; Frost, Karen; Carman, Nicholas; Church, Peter C; Ling, Simon C; Griffiths, Anne M

2018-03-01

To evaluate a large anti-tumor necrosis factor (TNF)-treated pediatric inflammatory bowel disease cohort for drug-induced liver injury (DILI) following presentation of an index case with suspected DILI with autoimmune features after infliximab exposure. To characterize the incidence, natural history, and risk factors for liver enzyme elevation with anti-TNF use. We reviewed the index case and performed a retrospective cohort study of 659 children receiving anti-TNF therapy between 2000 and 2015 at a tertiary pediatric inflammatory bowel disease center. Patients with alanine aminotransferase (ALT) ≥×2 the upper limit of normal were included. The incidence, evolution, and risk factors for liver injury were examined with univariate and multivariable proportional hazards regression. Causality was assessed using the Roussel-Uclaf Causality Assessment Method. The index case, a teenage girl with Crohn's disease, developed elevated liver enzymes and features of autoimmune hepatitis on liver biopsy 23 weeks after starting infliximab. The injury resolved entirely within 4 months of withdrawing infliximab without additional therapy. Overall, 7.7% of our cohort developed new ALT elevations while on anti-TNF. Most ALT elevations were mild and transient and attributable to alternate etiologies. No additional clear cases of autoimmune hepatitis were identified. Transient liver enzyme abnormalities are relatively common among anti-TNF-treated children. Anti-TNF-related DILI with autoimmune features is rare but must be recognized so that therapy can be stopped. Copyright © 2017 Elsevier Inc. All rights reserved.

Brief Report: Prevalence of Posttreatment Controller Phenotype Is Rare in HIV-Infected Persons After Stopping Antiretroviral Therapy.

PubMed

Perkins, Matthew J; Bradley, William P; Lalani, Tahaniyat; Agan, Brian K; Whitman, Timothy J; Ferguson, Tomas M; Okulicz, Jason F; Ganesan, Anuradha

2017-07-01

Posttreatment control of HIV infection is a rare phenomenon primarily described among those initiating treatment with antiretroviral therapy (ART) during early/acute HIV infection. We examined a large, well-characterized cohort of HIV-infected Department of Defense beneficiaries for the presence of posttreatment controllers (PTCs) whom we defined as individuals with sustained viral suppression for ≥6 months after discontinuation of ART. We defined those who became viremic within 6 months of discontinuing ART as rapid viremics (RVs) and compared demographic and clinical characteristics, CD4 counts, and viral loads prior, during, and after ART discontinuation between the 2 groups. From a cohort of 6070 patients, we identified 95 who had been treated with ART for 2 years or more who subsequently discontinued ART and had viral load assessments available after discontinuation. Four (4.2%) of these 95 met our definition of PTC. The duration of viral suppression off of ART ranged from 267 to 1058 days with 1 of the 4 restarting ART without having redeveloped a significant viremia. All 4 patients initiated ART during chronic HIV infection. Demographic and clinical characteristics of PTCs were similar to RVs. While posttreatment control has predominantly been described among individuals who initiated ART in early/acute HIV infection, we identified 4 PTCs who started ART during chronic infection suggesting that posttreatment control also occurs among such patients. The rarity of PTCs identified in our cohort is consistent with reports from previous studies.

Functional Testing of SLC26A4 Variants—Clinical and Molecular Analysis of a Cohort with Enlarged Vestibular Aqueduct from Austria

PubMed Central

Bernardinelli, Emanuele; Nofziger, Charity; Patsch, Wolfgang; Rasp, Gerd; Paulmichl, Markus; Dossena, Silvia

2018-01-01

The prevalence and spectrum of sequence alterations in the SLC26A4 gene, which codes for the anion exchanger pendrin, are population-specific and account for at least 50% of cases of non-syndromic hearing loss associated with an enlarged vestibular aqueduct. A cohort of nineteen patients from Austria with hearing loss and a radiological alteration of the vestibular aqueduct underwent Sanger sequencing of SLC26A4 and GJB2, coding for connexin 26. The pathogenicity of sequence alterations detected was assessed by determining ion transport and molecular features of the corresponding SLC26A4 protein variants. In this group, four uncharacterized sequence alterations within the SLC26A4 coding region were found. Three of these lead to protein variants with abnormal functional and molecular features, while one should be considered with no pathogenic potential. Pathogenic SLC26A4 sequence alterations were only found in 12% of patients. SLC26A4 sequence alterations commonly found in other Caucasian populations were not detected. This survey represents the first study on the prevalence and spectrum of SLC26A4 sequence alterations in an Austrian cohort and further suggests that genetic testing should always be integrated with functional characterization and determination of the molecular features of protein variants in order to unequivocally identify or exclude a causal link between genotype and phenotype. PMID:29320412

Comparison of labour induction with misoprostol and dinoprostone and characterization of uterine response based on electrohysterogram.

PubMed

Benalcazar-Parra, Carlos; Monfort-Orti, Rogelio; Ye-Lin, Yiyao; Prats-Boluda, Gema; Alberola-Rubio, Jose; Perales, Alfredo; Garcia-Casado, Javier

2017-12-17

The objective of this study is to compare the uterine activity response between women administered dinoprostone (prostaglandin E2) and misoprostol (prostaglandin E1) for induction of labour (IOL) by analysing not only the traditional obstetric data but also the parameters extracted from uterine electrohysterogram (EHG). Two cohorts were defined: misoprostol (25-µg vaginal tablets; 251 women) and dinoprostone cohort (10 mg vaginal inserts; 249 women). All the mothers were induced by a medical indication of a Bishop Score < = 6. The misoprostol cohort was associated with a shorter time to achieve active labour (p = .017) and vaginal delivery (p = .009) and with a higher percentage of vaginal delivery in less than 24 h in mothers with a very unfavourable cervix score (risk ratio (RR): 1.41, IC95% 1.17-1.69, p = .002). Successful inductions with misoprostol showed EHG parameter values significantly higher than basal state for amplitude and pseudo Montevideo units (PMU) 60' after drug administration, while spectral parameters significantly increased after 150'. This response was not observed in failed inductions. In the successful dinoprostone group, the duration and number of contractions increased significantly after 120', PMU did so after 180', and no significant differences were found for spectral parameters, possibly due to the slower pharmacokinetics of this drug. Successful inductions of labour by misoprostol are associated with earlier effective contractions than in labours induced by dinoprostone.

Case-control analysis of truncating mutations in DNA damage response genes connects TEX15 and FANCD2 with hereditary breast cancer susceptibility.

PubMed

Mantere, Tuomo; Tervasmäki, Anna; Nurmi, Anna; Rapakko, Katrin; Kauppila, Saila; Tang, Jiangbo; Schleutker, Johanna; Kallioniemi, Anne; Hartikainen, Jaana M; Mannermaa, Arto; Nieminen, Pentti; Hanhisalo, Riitta; Lehto, Sini; Suvanto, Maija; Grip, Mervi; Jukkola-Vuorinen, Arja; Tengström, Maria; Auvinen, Päivi; Kvist, Anders; Borg, Åke; Blomqvist, Carl; Aittomäki, Kristiina; Greenberg, Roger A; Winqvist, Robert; Nevanlinna, Heli; Pylkäs, Katri

2017-04-06

Several known breast cancer susceptibility genes encode proteins involved in DNA damage response (DDR) and are characterized by rare loss-of-function mutations. However, these explain less than half of the familial cases. To identify novel susceptibility factors, 39 rare truncating mutations, identified in 189 Northern Finnish hereditary breast cancer patients in parallel sequencing of 796 DDR genes, were studied for disease association. Mutation screening was performed for Northern Finnish breast cancer cases (n = 578-1565) and controls (n = 337-1228). Mutations showing potential cancer association were analyzed in additional Finnish cohorts. c.7253dupT in TEX15, encoding a DDR factor important in meiosis, associated with hereditary breast cancer (p = 0.018) and likely represents a Northern Finnish founder mutation. A deleterious c.2715 + 1G > A mutation in the Fanconi anemia gene, FANCD2, was over two times more common in the combined Finnish hereditary cohort compared to controls. A deletion (c.640_644del5) in RNF168, causative for recessive RIDDLE syndrome, had high prevalence in majority of the analyzed cohorts, but did not associate with breast cancer. In conclusion, truncating variants in TEX15 and FANCD2 are potential breast cancer risk factors, warranting further investigations in other populations. Furthermore, high frequency of RNF168 c.640_644del5 indicates the need for its testing in Finnish patients with RIDDLE syndrome symptoms.

Occupational factors and pancreatic cancer.

PubMed Central

Norell, S; Ahlbom, A; Olin, R; Erwald, R; Jacobson, G; Lindberg-Navier, I; Wiechel, K L

1986-01-01

The relation between occupational factors and pancreatic cancer has been studied by two different approaches: a population based case-control study with two series of controls and a retrospective cohort study based on register data. With both approaches, some support was found for an association with occupational exposure to petroleum products. Associations were also indicated with exposure to paint thinner (case-control study) and work in painting and in paint and varnish factories (cohort study), for exposure to detergents, floor cleaning agents, or polish (case-control study) and with floor polishing or window cleaning (cohort study), and for exposure to refuse (case-control study) and work in refuse disposal plants (cohort study). PMID:3790458

Improving survey response rates from parents in school-based research using a multi-level approach.

PubMed

Schilpzand, Elizabeth J; Sciberras, Emma; Efron, Daryl; Anderson, Vicki; Nicholson, Jan M

2015-01-01

While schools can provide a comprehensive sampling frame for community-based studies of children and their families, recruitment is challenging. Multi-level approaches which engage multiple school stakeholders have been recommended but few studies have documented their effects. This paper compares the impact of a standard versus enhanced engagement approach on multiple indicators of recruitment: parent response rates, response times, reminders required and sample characteristics. Parents and teachers were distributed a brief screening questionnaire as a first step for recruitment to a longitudinal study, with two cohorts recruited in consecutive years (cohort 1 2011, cohort 2 2012). For cohort 2, additional engagement strategies included the use of pre-notification postcards, improved study materials, and recruitment progress graphs provided to school staff. Chi-square and t-tests were used to examine cohort differences. Compared to cohort 1, a higher proportion of cohort 2 parents responded to the survey (76% versus 69%; p < 0.001), consented to participate (71% versus 56%; p < 0.001), agreed to teacher participation (90% versus 82%; p < 0.001) and agreed to follow-up contact (91% versus 80%; p < 0.001). Fewer cohort 2 parents required reminders (52% versus 63%; p < 0.001), and cohort 2 parents responded more promptly than cohort 1 parents (mean difference: 19.4 days, 95% CI: 18.0 to 20.9, p < 0.001). These results illustrate the value of investing in a relatively simple multi-level strategy to maximise parent response rates, and potentially reduce recruitment time and costs.

A Cohort, Is a Cohort, Is a Cohort...or Is It?

ERIC Educational Resources Information Center

Pemberton, Cynthia Lee A.; Akkary, Rima Karami

2010-01-01

This paper presents findings from a multi-year qualitative study based upon life-history narratives of women pursuing doctoral degrees in Educational Leadership. This paper focuses on findings specific to educational cohort models, and suggests that perhaps, at least for women, naturally emergent cohorts--born of relationships of choice--may be…

Meat consumption and risk of lung cancer: evidence from observational studies

PubMed Central

Yang, W. S.; Wong, M. Y.; Vogtmann, E.; Tang, R. Q.; Xie, L.; Yang, Y. S.; Wu, Q. J.; Zhang, W.; Xiang, Y. B.

2012-01-01

Background A number of epidemiological studies have reported inconsistent findings on the association between meat consumption and lung cancer. Design We therefore conducted a systematic review and meta-analysis to investigate the relationship between meat consumption and lung cancer risk in epidemiological studies. Results Twenty-three case–control and 11 cohort studies were included. All studies adjusted for smoking or conducted in never smokers. The summary relative risks (RRs) of lung cancer for the highest versus lowest intake categories were 1.35 (95% confidence interval (CI) 1.08–1.69) for total meat, 1.34 (95% CI 1.18–1.52) for red meat, and 1.06 (95% CI 0.90–1.25) for processed meat. An inverse association was found between poultry intake and lung cancer (RR = 0.91, 95% CI 0.85–0.97), but not for total white meat (RR = 1.06, 95% CI 0.82–1.37) or fish (RR = 1.01, 95% CI 0.96–1.07). Conclusions The relationship between meat intake and lung cancer risk appears to depend on the types of meat consumed. A high intake of red meat may increase the risk of lung cancer by about 35%, while a high intake of poultry decreases the risk by about 10%. More well-designed cohort studies on meat mutagens or heme iron, meat cooking preferences, and doneness level are needed to fully characterize this meat–lung cancer association. PMID:22855553

Piecewise exponential survival times and analysis of case-cohort data.

PubMed

Li, Yan; Gail, Mitchell H; Preston, Dale L; Graubard, Barry I; Lubin, Jay H

2012-06-15

Case-cohort designs select a random sample of a cohort to be used as control with cases arising from the follow-up of the cohort. Analyses of case-cohort studies with time-varying exposures that use Cox partial likelihood methods can be computer intensive. We propose a piecewise-exponential approach where Poisson regression model parameters are estimated from a pseudolikelihood and the corresponding variances are derived by applying Taylor linearization methods that are used in survey research. The proposed approach is evaluated using Monte Carlo simulations. An illustration is provided using data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of male smokers in Finland, where a case-cohort study of serum glucose level and pancreatic cancer was analyzed. Copyright © 2012 John Wiley & Sons, Ltd.

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

PubMed

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

2015-11-01

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

Clinical and Biological Insights from the University of California San Francisco Prospective and Longitudinal Cohort.

PubMed

Benn, Bryan S; Lehman, Zoe; Kidd, Sharon A; Ho, Melissa; Sun, Sara; Ramstein, Joris; Arger, Nicholas K; Nguyen, Christine P; Su, Robert; Gomez, Antonio; Gelfand, Jeffrey M; Koth, Laura L

2017-10-01

Sarcoidosis is a systemic inflammatory disease characterized by non-necrotizing granulomas in involved organs, most commonly the lung. Description of patient characteristics in the Western United States is limited. Furthermore, blood-based measures that relate to clinical sarcoidosis phenotypes are lacking. We present an analysis of a prospective, longitudinal sarcoidosis cohort at a Northern Californian academic medical center. We enrolled 126 sarcoidosis subjects and 64 healthy controls and recorded baseline demographic and clinical characteristics. We used regression models to identify factors independently associated with pulmonary physiology. We tested whether blood transcript levels at study entry could relate to longitudinal changes in pulmonary physiology. White, non-Hispanics composed ~70% of subjects. Hispanics and Blacks had a diagnostic biopsy at an age ~7 years younger than whites. Obstructive, but not restrictive, physiology characterized Scadding Stage IV patients. Subjects reporting use of immunosuppression had worse FEV1%p, FVC%p, and DLCO%p compared to subjects never treated, regardless of Scadding stage. We defined sarcoidosis disease activity by a drop in pulmonary function over 36 months and found that subjects meeting this definition had significant repression of blood gene transcripts related to T cell receptor signaling pathways, referred to as the "TCR factor." Obstructive pulmonary physiology defined Stage IV patients which were mostly white, non-Hispanics. Genes comprising the composite gene expression score, TCR factor, may represent a blood-derived measure of T-cell activity and an indirect measure of active sarcoidosis inflammation. Validation of this measure could translate into individualized treatment for sarcoidosis patients.

Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles

PubMed Central

Baron, Ralf; Maier, Christoph; Attal, Nadine; Binder, Andreas; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B.; Haanpää, Maija; Hansson, Per; Hüllemann, Philipp; Jensen, Troels S.; Freynhagen, Rainer; Kennedy, Jeffrey D.; Magerl, Walter; Mainka, Tina; Reimer, Maren; Rice, Andrew S.C.; Segerdahl, Märta; Serra, Jordi; Sindrup, Sören; Sommer, Claudia; Tölle, Thomas; Vollert, Jan; Treede, Rolf-Detlef

2016-01-01

Abstract Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of pain-related sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profiles might respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroups with characteristic sensory profiles were identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combination with pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders. PMID:27893485

Muscle imaging findings in GNE myopathy.

PubMed

Tasca, Giorgio; Ricci, Enzo; Monforte, Mauro; Laschena, Francesco; Ottaviani, Pierfrancesco; Rodolico, Carmelo; Barca, Emanuele; Silvestri, Gabriella; Iannaccone, Elisabetta; Mirabella, Massimiliano; Broccolini, Aldobrando

2012-07-01

GNE myopathy (MIM 600737) is an autosomal recessive muscle disease caused by mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. Besides the typical phenotype, characterized by the initial involvement of the distal leg muscles that eventually spreads proximally with sparing of the quadriceps, uncommon presentations with a non-canonical clinical phenotype, unusual muscle biopsy findings or both are increasingly recognized. The aim of our study was to characterize the imaging pattern of pelvic and lower limb muscles in GNE myopathy, thus providing additional diagnostic clues useful in the identification of patients with atypical features. We retrospectively evaluated muscle MRI and CT scans of a cohort of 13 patients heterogeneous for GNE mutations and degree of clinical severity. We found that severe involvement of the biceps femoris short head and, to a lesser extent, of the gluteus minimus, tibialis anterior, extensor hallucis and digitorum longus, soleus and gastrocnemius medialis was consistently present even in patients with early or atypical disease. The vastus lateralis, not the entire quadriceps, was the only muscle spared in advanced stages, while the rectus femoris, vastus intermedius and medialis showed variable signs of fatty replacement. Younger patients showed hyperintensities on T2-weighted sequences in muscles with a normal or, more often, abnormal T1-weighted signal. Our results define a pattern of muscle involvement that appears peculiar to GNE myopathy. Although these findings need to be further validated in a larger cohort, we believe that the recognition of this pattern may be instrumental in the initial clinical assessment of patients with possible GNE myopathy.

Molecular characterization of colorectal cancer patients and concomitant patient-derived tumor cell establishment

PubMed Central

Kim, Seung Tae; Kim, Sun Young; Kim, Nayoung K.D.; Jang, Jiryeon; Kang, Mihyun; Jang, Hyojin; Ahn, Soomin; Kim, Seok Hyeong; Park, Yoona; Cho, Yong Beom; Heo, Jeong Wook; Lee, Woo Yong; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Park, Woong-Yang; Lee, Jeeyun; Kim, Hee Cheol

2016-01-01

Background We aimed to establish a prospectively enrolled colorectal cancer (CRC) cohort for targeted sequencing of primary tumors from CRC patients. In parallel, we established collateral PDC models from the matched primary tumor tissues, which may be later used as preclinical models for genome-directed targeted therapy experiments. Results In all, we identified 27 SNVs in the 6 genes such as PIK3CA (N = 16), BRAF (N = 6), NRAS (N = 2), and CTNNB1 (N = 1), PTEN (N = 1), and ERBB2 (N = 1). RET-NCOA4 translocation was observed in one out of 105 patients (0.9%). PDC models were successfully established from 62 (55.4%) of the 112 samples. To confirm the genomic features of various tumor cells, we compared variant allele frequency results of the primary tumor and progeny PDCs. The Pearson correlation coefficient between the variants from primary tumor cells and PDCs was 0.881. Methods Between April 2014 and June 2015, 112 patients with CRC who underwent resection of the primary tumor were enrolled in the SMC Oncology Biomarker study. The PDC culture protocol was performed for all eligible patients. All of the primary tumors from the 112 patients who provided written informed consent were genomically sequenced with targeted sequencing. In parallel, PDC establishment was attempted for all sequenced tumors. Conclusions We have prospectively sequenced a CRC cohort of 105 patients and successfully established 62 PDC in parallel. Each genomically characterized PDCs can be used as a preclinical model especially in rare genomic alteration event. PMID:26909603

The RNA-Binding Protein Musashi1 Affects Medulloblastoma Growth via a Network of Cancer-Related Genes and Is an Indicator of Poor Prognosis

PubMed Central

Vo, Dat T.; Subramaniam, Dharmalingam; Remke, Marc; Burton, Tarea L.; Uren, Philip J.; Gelfond, Jonathan A.; de Sousa Abreu, Raquel; Burns, Suzanne C.; Qiao, Mei; Suresh, Uthra; Korshunov, Andrey; Dubuc, Adrian M.; Northcott, Paul A.; Smith, Andrew D.; Pfister, Stefan M.; Taylor, Michael D.; Janga, Sarath C.; Anant, Shrikant; Vogel, Christine; Penalva, Luiz O.F.

2013-01-01

Musashi1 (Msi1) is a highly conserved RNA-binding protein that is required during the development of the nervous system. Msi1 has been characterized as a stem cell marker, controlling the balance between self-renewal and differentiation, and has also been implicated in tumorigenesis, being highly expressed in multiple tumor types. We analyzed Msi1 expression in a large cohort of medulloblastoma samples and found that Msi1 is highly expressed in tumor tissue compared with normal cerebellum. Notably, high Msi1 expression levels proved to be a sign of poor prognosis. Msi1 expression was determined to be particularly high in molecular subgroups 3 and 4 of medulloblastoma. We determined that Msi1 is required for tumorigenesis because inhibition of Msi1 expression by small-interfering RNAs reduced the growth of Daoy medulloblastoma cells in xenografts. To characterize the participation of Msi1 in medulloblastoma, we conducted different high-throughput analyses. Ribonucleoprotein immunoprecipitation followed by microarray analysis (RIP-chip) was used to identify mRNA species preferentially associated with Msi1 protein in Daoy cells. We also used cluster analysis to identify genes with similar or opposite expression patterns to Msi1 in our medulloblastoma cohort. A network study identified RAC1, CTGF, SDCBP, SRC, PRL, and SHC1 as major nodes of an Msi1-associated network. Our results suggest that Msi1 functions as a regulator of multiple processes in medulloblastoma formation and could become an important therapeutic target. PMID:22985791

Prospective Associations of Maternal Dietary Patterns and Postpartum Mental Health in a Multi-Ethnic Asian Cohort: The Growing up in Singapore towards Healthy Outcomes (GUSTO) Study.

PubMed

Teo, Cherlyen; Chia, Ai-Ru; Colega, Marjorelee T; Chen, Ling-Wei; Fok, Doris; Pang, Wei Wei; Godfrey, Keith M; Tan, Kok Hian; Yap, Fabian; Shek, Lynette Pei-Chi; Chong, Yap-Seng; Meaney, Michael; Chen, Helen; Chong, Mary Foong-Fong

2018-03-02

Diet in the first month postpartum, otherwise known as "the confinement diet" in Asia, has unique characteristics that are influenced by traditions, cultures, and beliefs. We aimed to characterize dietary patterns during confinement period in a multi-ethnic Asian cohort and examined their associations with postpartum depression (PPD) and anxiety (PPA). Dietary intakes of 490 women were ascertained in the first month postpartum using 3-day food diaries and dietary patterns were derived by factor analysis. Participants completed the Edinburgh Postnatal Depression Scale (EPDS) and State-Trait Anxiety Inventory (STAI) at three months' postpartum; higher scores are indicative of more depressive and anxiety symptoms, respectively. Four dietary patterns were identified: Traditional-Chinese-Confinement diet, Traditional-Indian-Confinement diet, Eat-Out diet and Soup-Vegetables-Fruits diet. The Traditional-Indian-Confinement diet was associated with less PPD symptoms [β (95% CI) -0.62 (-1.16, -0.09) EPDS score per SD increase in diet score] and a non-significant trend with reduced probable PPD (EPDS scores ≥ 13) [OR (95% CI) 0.56 (0.31, 1.01)]. The Soup-Vegetables-Fruits diet was associated with less PPA symptoms [β (95% CI) -1.49 (-2.56, -0.42) STAI-state score]. No associations were observed for other dietary patterns. Independent of ethnicity, adherence to the Traditional-Indian-Confinement diet that is characterized by intake of herbs and legumes, and Soup-Vegetables-Fruits diet high in fruits, vegetables and fish during the postpartum period were associated with less PPD and PPA symptoms, respectively.

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

PubMed

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

2012-01-01

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

Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles.

PubMed

Baron, Ralf; Maier, Christoph; Attal, Nadine; Binder, Andreas; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B; Haanpää, Maija; Hansson, Per; Hüllemann, Philipp; Jensen, Troels S; Freynhagen, Rainer; Kennedy, Jeffrey D; Magerl, Walter; Mainka, Tina; Reimer, Maren; Rice, Andrew S C; Segerdahl, Märta; Serra, Jordi; Sindrup, Sören; Sommer, Claudia; Tölle, Thomas; Vollert, Jan; Treede, Rolf-Detlef

2017-02-01

Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of pain-related sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profiles might respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroups with characteristic sensory profiles were identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combination with pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders.

Using fractional exhaled nitric oxide (FeNO) to diagnose steroid-responsive disease and guide asthma management in routine care.

PubMed

Price, David; Ryan, Dermot; Burden, Annie; Von Ziegenweidt, Julie; Gould, Shuna; Freeman, Daryl; Gruffydd-Jones, Kevin; Copland, Anne; Godley, Clifford; Chisholm, Alison; Thomas, Mike

2013-11-07

Fractional exhaled nitric oxide (FeNO) is a surrogate marker of eosinophilic airway inflammation and good predictor of corticosteroid response. To evaluate how FeNO is being used to guide primary care asthma management in the United Kingdom (UK) with a view to devising practical algorithms for the use of FeNO in the diagnosis of steroid-responsive disease and to guide on-going asthma management. Eligible patients (n = 678) were those in the Optimum Patient Care Research Database (OPCRD) aged 4-80 years who, at an index date, had their first FeNO assessment via NIOX MINO® or Flex®. Eligible practices were those using FeNO measurement in at least ten patients during the study period. Patients were characterized over a one-year baseline period immediately before the index date. Outcomes were evaluated in the year immediately following index date for two patient cohorts: (i) those in whom FeNO measurement was being used to identify steroid-responsive disease and (ii) those in whom FeNO monitoring was being used to guide on-going asthma management. Outcomes for cohort (i) were incidence of new ICS initiation at, or within the one-month following, their first FeNO measurement, and ICS dose during the outcome year. Outcomes for cohort (ii) were adherence, change in adherence (from baseline) and ICS dose. In cohort (i) (n = 304) the higher the FeNO category, the higher the percentage of patients that initiated ICS at, or in the one month immediately following, their first FeNO measurement: 82%, 46% and 26% of patients with high, intermediate and low FeNO, respectively. In cohort (ii) (n = 374) high FeNO levels were associated with poorer baseline adherence (p = 0.005) but greater improvement in adherence in the outcome year (p = 0.017). Across both cohorts, patients with high FeNO levels were associated with significantly higher ICS dosing (p < 0.001). In the UK, FeNO is being used in primary practice to guide ICS initiation and dosing decisions and to identify poor ICS adherence. Simple algorithms to guide clinicians in the practical use of FeNO could improved diagnostic accuracy and better tailored asthma regimens.

Severe impingement of lumbar disc replacements increases the functional biological activity of polyethylene wear debris.

PubMed

Baxter, Ryan M; Macdonald, Daniel W; Kurtz, Steven M; Steinbeck, Marla J

2013-06-05

Wear, oxidation, and particularly rim impingement damage of ultra-high molecular weight polyethylene total disc replacement components have been observed following surgical revision. However, neither in vitro testing nor retrieval-based evidence has shown the effect(s) of impingement on the characteristics of polyethylene wear debris. Thus, we sought to determine (1) differences in polyethylene particle size, shape, number, or biological activity that correspond to mild or severe rim impingement and (2) in an analysis of all total disc replacements, regardless of impingement classification, whether there are correlations between the extent of regional damage and the characteristics of polyethylene wear debris. The extent of dome and rim damage was characterized for eleven retrieved polyethylene cores obtained at revision surgery after an average duration of implantation of 9.7 years (range, 4.6 to 16.1 years). Polyethylene wear debris was isolated from periprosthetic tissues with use of nitric acid and was imaged with use of environmental scanning electron microscopy. Subsequently, particle size, shape, number, biological activity, and chronic inflammation scores were determined. Grouping of particles by size ranges that represented high biological relevance (<0.1 to 1-μm particles), intermediate biological relevance (1 to 10-μm particles), and low biological relevance (>10-μm particles) revealed an increased volume fraction of particles in the <0.1 to 1-μm and 1 to 10-μm size ranges in the mild-impingement cohort as compared with the severe-impingement cohort. The increased volume fractions resulted in a higher specific biological activity per unit particle volume in the mild-impingement cohort than in the severe-impingement cohort. However, functional biological activity, which is normalized by particle volume (mm3/g of tissue), was significantly higher in the severe-impingement cohort. This increase was due to a larger volume of particles in all three size ranges. In both cohorts, the functional biological activity correlated with the chronic inflammatory response, and the extent of rim penetration positively correlated with increasing particle size, number, and functional biological activity. The results of this study suggest that severe rim impingement increases the production of biologically relevant particles from motion-preserving lumbar total disc replacement components. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Severe Impingement of Lumbar Disc Replacements Increases the Functional Biological Activity of Polyethylene Wear Debris

PubMed Central

Baxter, Ryan M.; MacDonald, Daniel W.; Kurtz, Steven M.; Steinbeck, Marla J.

2013-01-01

Background: Wear, oxidation, and particularly rim impingement damage of ultra-high molecular weight polyethylene total disc replacement components have been observed following surgical revision. However, neither in vitro testing nor retrieval-based evidence has shown the effect(s) of impingement on the characteristics of polyethylene wear debris. Thus, we sought to determine (1) differences in polyethylene particle size, shape, number, or biological activity that correspond to mild or severe rim impingement and (2) in an analysis of all total disc replacements, regardless of impingement classification, whether there are correlations between the extent of regional damage and the characteristics of polyethylene wear debris. Methods: The extent of dome and rim damage was characterized for eleven retrieved polyethylene cores obtained at revision surgery after an average duration of implantation of 9.7 years (range, 4.6 to 16.1 years). Polyethylene wear debris was isolated from periprosthetic tissues with use of nitric acid and was imaged with use of environmental scanning electron microscopy. Subsequently, particle size, shape, number, biological activity, and chronic inflammation scores were determined. Results: Grouping of particles by size ranges that represented high biological relevance (<0.1 to 1-μm particles), intermediate biological relevance (1 to 10-μm particles), and low biological relevance (>10-μm particles) revealed an increased volume fraction of particles in the <0.1 to 1-μm and 1 to 10-μm size ranges in the mild-impingement cohort as compared with the severe-impingement cohort. The increased volume fractions resulted in a higher specific biological activity per unit particle volume in the mild-impingement cohort than in the severe-impingement cohort. However, functional biological activity, which is normalized by particle volume (mm3/g of tissue), was significantly higher in the severe-impingement cohort. This increase was due to a larger volume of particles in all three size ranges. In both cohorts, the functional biological activity correlated with the chronic inflammatory response, and the extent of rim penetration positively correlated with increasing particle size, number, and functional biological activity. Conclusions: The results of this study suggest that severe rim impingement increases the production of biologically relevant particles from motion-preserving lumbar total disc replacement components. Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID:23780545

Comparison of Smoking History Patterns Among African American and White Cohorts in the United States Born 1890 to 1990.

PubMed

Holford, Theodore R; Levy, David T; Meza, Rafael

2016-04-01

Characterizing smoking history patterns summarizes life course exposure for birth cohorts, essential for evaluating the impact of tobacco control on health. Limited attention has been given to patterns among African Americans. Life course smoking histories of African Americans and whites were estimated beginning with the 1890 birth cohort. Estimates of smoking initiation and cessation probabilities, and intensity can be used as a baseline for studying smoking intervention strategies that target smoking exposure. US National Health Interview Surveys conducted from 1965 to 2012 yielded cross-sectional information on current smoking behavior among African Americans and whites. Additional detail for smokers including age at initiation, age at cessation and smoking intensity were available in some surveys and these were used to construct smoking histories for participants up to the date that they were interviewed. Age-period-cohort models with constrained natural splines provided estimates of current, former and never-smoker prevalence in cohorts beginning in 1890. This approach yielded yearly estimates of initiation, cessation and smoking intensity by age for each birth cohort. Smoking initiation probabilities tend to be lower among African Americans compared to whites, and cessation probabilities also were generally lower. Higher initiation leads to higher smoking prevalence among whites in younger ages, but lower cessation leads to higher prevalence at older ages in blacks, when adverse health effects of smoking become most apparent. These estimates provide a summary that can be used to better understand the effects of changes in smoking behavior following publication of the Surgeon General's Report in 1964. A novel method of estimating smoking histories was applied to data from the National Health Interview Surveys, which provided an extensive summary of the smoking history in this population following publication of the Surgeon General's Report in 1964. The results suggest that some of the existing disparities in smoking-related disease may be due to the lower cessation rates in African Americans compared to whites. However, the number of cigarettes smoked is also lower among African Americans. Further work is needed to determine mechanisms by which smoking duration and intensity can account for racial disparities in smoking-related diseases. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Quality standards for epidemiologic cohort studies : An evaluated catalogue of requirements for the conduct and preparation of cohort studies].

PubMed

Schmidt, Carsten Oliver; Krabbe, Christine E M; Schössow, Janka; Berger, Klaus; Enzenbach, Cornelia; Kamtsiuris, Panagiotis; Schöne, Gina; Houben, Robin; Meisinger, Christa; Bamberg, Fabian; Hendel, Thomas; Selder, Sonja; Nonnemacher, Michael; Moebus, Susanne; Stausberg, Jürgen

2018-01-01

Cohort studies are a longitudinal observational study type. They are firmly established within epidemiology to assess the course of diseases and risk factors. Yet, standards to describe and evaluate quality characteristics of cohort studies need further development. Within the TMF ("Technologie- und Methodenplattform für die vernetzte medizinische Forschung e. V.") project "Quality management standards in cohort studies", a catalogue of requirements was compiled and evaluated, focusing on the preparation and conduct of epidemiologic cohort studies. The catalogue of requirements was established based on a consensus process between representatives of seven German epidemiologic cohort studies. For this purpose, a set of expert meetings (telephone, face-to-face, web-based) was conducted and the importance of each element of the catalogue was assessed as well as its implementation. A catalogue of requirements with 138 requirements was consented. It is structured into ten sections: 1. Study documentation; 2. Selection of instruments; 3. Study implementation, 4. Organizational structure; 5. Qualification and certification; 6. Participant recruitment; 7. Preparation, conduct and follow-up processing of examinations; 8. Study logistics and maintenance, 9. Data capture and data management; 10. Reporting and monitoring. In total, 41 elements were categorized as being essential, 91 as important, and 6 as less important. The catalogue of requirements provides a guideline to improve the preparation and operation of cohort studies. The evaluation of the importance and degree of implementation of requirements depended on the study design. With adaptations, the catalogue might be transferable to other study types.

Cohort Profile Update: The China Jintan Child Cohort Study

PubMed Central

Liu, Jianghong; Cao, Siyuan; Chen, Zehang; Raine, Adrian; Hanlon, Alexandra; Ai, Yuexian; Zhou, Guoping; Yan, Chonghuai; Leung, Patrick W; McCauley, Linda; Pinto-Martin, Jennifer

2015-01-01

The China Jintan Child Cohort study began in 2004 with 1656 pre-school participants and a research focus on studying the impact of environmental exposures, such as lead, on children’s neurobehavioural outcomes. This population cohort now includes around 1000 of the original participants, who have been assessed three times over a period of 10 years. Since the original IJE cohort profile publication in 2010, participants have experienced a critical developmental transition from pre-school to school age and then adolescence. The study has also witnessed an increase in breadth and depth of data collection from the original aim of risk assessment. This cohort has added new directions to investigate the mechanisms and protective factors for the relationship between early health factors and child physical and mental health outcomes, with an emphasis on neurobehavioural consequences. The study now encompasses 11 domains, composed of repeated measures of the original variables and new domains of biomarkers, sleep, psychophysiology, neurocognition, personality, peer relationship, mindfulness and family dynamics. Depth of evaluation has increased from parent/teacher report to self/peer report and intergenerational family report. Consequently, the cohort has additional directions to include: (i) classmates of the original cohort participants for peer relationship assessment; and (ii) parental and grandparental measures to assess personality and dynamics within families. We welcome interest in our study and ask investigators to contact the corresponding author for additional information on data acquisition. PMID:26323725

Serum Metabolomic Profiling in Acute Alcoholic Hepatitis Identifies Multiple Dysregulated Pathways

PubMed Central

Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N.; Cooper, Sara; Malik, Shahid; Behari, Jaideep

2014-01-01

Background and Objectives While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. Methods This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Results Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Conclusion Severe AAH is characterized by a distinct metabolic phenotype spanning multiple pathways. Metabolomics profiling revealed a panel of biomarkers for disease prognosis, and future studies are planned to validate these findings in larger cohorts of patients with severe AAH. PMID:25461442

A CNGB1 Frameshift Mutation in Papillon and Phalène Dogs with Progressive Retinal Atrophy

PubMed Central

Ahonen, Saija J.; Arumilli, Meharji; Lohi, Hannes

2013-01-01

Progressive retinal degenerations are the most common causes of complete blindness both in human and in dogs. Canine progressive retinal atrophy (PRA) or degeneration resembles human retinitis pigmentosa (RP) and is characterized by a progressive loss of rod photoreceptor cells followed by a loss of cone function. The primary clinical signs are detected as vision impairment in a dim light. Although several genes have been associated with PRAs, there are still PRAs of unknown genetic cause in many breeds, including Papillons and Phalènes. We have performed a genome wide association and linkage studies in cohort of 6 affected Papillons and Phalènes and 14 healthy control dogs to map a novel PRA locus on canine chromosome 2, with a 1.9 Mb shared homozygous region in the affected dogs. Parallel exome sequencing of a trio identified an indel mutation, including a 1-bp deletion, followed by a 6-bp insertion in the CNGB1 gene. This mutation causes a frameshift and premature stop codon leading to probable nonsense mediated decay (NMD) of the CNGB1 mRNA. The mutation segregated with the disease and was confirmed in a larger cohort of 145 Papillons and Phalènes (PFisher = 1.4×10−8) with a carrier frequency of 17.2 %. This breed specific mutation was not present in 334 healthy dogs from 10 other breeds or 121 PRA affected dogs from 44 other breeds. CNGB1 is important for the photoreceptor cell function its defects have been previously associated with retinal degeneration in both human and mouse. Our study indicates that a frameshift mutation in CNGB1 is a cause of PRA in Papillons and Phalènes and establishes the breed as a large functional animal model for further characterization of retinal CNGB1 biology and possible retinal gene therapy trials. This study enables also the development of a genetic test for breeding purposes. PMID:24015210

Association of residential greenness with obesity and physical activity in a US cohort of women.

PubMed

Villeneuve, Paul J; Jerrett, Michael; Su, Jason G; Weichenthal, Scott; Sandler, Dale P

2018-01-01

There is evidence of several health benefits associated with neighborhood greenness, but reasons for this are unclear. Studies have found that those who live in greener neighborhoods are more physically active, and have lower rates of obesity. Relatively few studies have attempted to characterize associations between greenness and both obesity and physical activity concurrently, or among women who are at higher risk of developing cancer and for whom physical activity may be important for primary prevention. To address these gaps, we undertook a cross-sectional analysis of data from 50,884 women who enrolled in the Sister Study between 2003 and 2009. This cohort includes women aged 35-74 whose sister had been diagnosed with breast cancer. Residential measures of greenness were determined using the US National Land Cover database. Logistic regression was used to characterize associations between greenness, obesity, and physical activity. Adjustments were made for other possible confounders. Women who lived in areas with the highest tertile of greenness (based on a 500m buffer) had a reduced risk of obesity (body mass index (BMI) ≥ 30) relative to those in the lowest tertile (odds ratio (OR) = 0.83, 95% CI = 0.79-0.87). We also found that those the upper tertile of greenness were 17% more likely to expend more than 67.1 metabolic equivalent (MET) hours per week when compared to those in the lowest tertile (OR = 1.17, 95% CI = 1.10-1.23). Beneficial associations between greenness and both obesity and physical activity were observed in urban and rural areas, and regionally, stronger associations were observed in the western census region in the US. Mediation analyses indicated that physical activity attenuated the association between greenness and obesity by 32%. Our findings indicate that, amongst US adult women at higher risks of breast cancer, residential proximity to greenness may help mitigate against sedentary behaviors that increase the risk of chronic disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Ancestral Components of Admixed Genomes in a Mexican Cohort

PubMed Central

Johnson, Nicholas A.; Coram, Marc A.; Shriver, Mark D.; Romieu, Isabelle; Barsh, Gregory S.; London, Stephanie J.; Tang, Hua

2011-01-01

For most of the world, human genome structure at a population level is shaped by interplay between ancient geographic isolation and more recent demographic shifts, factors that are captured by the concepts of biogeographic ancestry and admixture, respectively. The ancestry of non-admixed individuals can often be traced to a specific population in a precise region, but current approaches for studying admixed individuals generally yield coarse information in which genome ancestry proportions are identified according to continent of origin. Here we introduce a new analytic strategy for this problem that allows fine-grained characterization of admixed individuals with respect to both geographic and genomic coordinates. Ancestry segments from different continents, identified with a probabilistic model, are used to construct and study “virtual genomes” of admixed individuals. We apply this approach to a cohort of 492 parent–offspring trios from Mexico City. The relative contributions from the three continental-level ancestral populations—Africa, Europe, and America—vary substantially between individuals, and the distribution of haplotype block length suggests an admixing time of 10–15 generations. The European and Indigenous American virtual genomes of each Mexican individual can be traced to precise regions within each continent, and they reveal a gradient of Amerindian ancestry between indigenous people of southwestern Mexico and Mayans of the Yucatan Peninsula. This contrasts sharply with the African roots of African Americans, which have been characterized by a uniform mixing of multiple West African populations. We also use the virtual European and Indigenous American genomes to search for the signatures of selection in the ancestral populations, and we identify previously known targets of selection in other populations, as well as new candidate loci. The ability to infer precise ancestral components of admixed genomes will facilitate studies of disease-related phenotypes and will allow new insight into the adaptive and demographic history of indigenous people. PMID:22194699

Modeling and Classification of Kinetic Patterns of Dynamic Metabolic Biomarkers in Physical Activity

PubMed Central

Breit, Marc; Netzer, Michael

2015-01-01

The objectives of this work were the classification of dynamic metabolic biomarker candidates and the modeling and characterization of kinetic regulatory mechanisms in human metabolism with response to external perturbations by physical activity. Longitudinal metabolic concentration data of 47 individuals from 4 different groups were examined, obtained from a cycle ergometry cohort study. In total, 110 metabolites (within the classes of acylcarnitines, amino acids, and sugars) were measured through a targeted metabolomics approach, combining tandem mass spectrometry (MS/MS) with the concept of stable isotope dilution (SID) for metabolite quantitation. Biomarker candidates were selected by combined analysis of maximum fold changes (MFCs) in concentrations and P-values resulting from statistical hypothesis testing. Characteristic kinetic signatures were identified through a mathematical modeling approach utilizing polynomial fitting. Modeled kinetic signatures were analyzed for groups with similar behavior by applying hierarchical cluster analysis. Kinetic shape templates were characterized, defining different forms of basic kinetic response patterns, such as sustained, early, late, and other forms, that can be used for metabolite classification. Acetylcarnitine (C2), showing a late response pattern and having the highest values in MFC and statistical significance, was classified as late marker and ranked as strong predictor (MFC = 1.97, P < 0.001). In the class of amino acids, highest values were shown for alanine (MFC = 1.42, P < 0.001), classified as late marker and strong predictor. Glucose yields a delayed response pattern, similar to a hockey stick function, being classified as delayed marker and ranked as moderate predictor (MFC = 1.32, P < 0.001). These findings coincide with existing knowledge on central metabolic pathways affected in exercise physiology, such as β-oxidation of fatty acids, glycolysis, and glycogenolysis. The presented modeling approach demonstrates high potential for dynamic biomarker identification and the investigation of kinetic mechanisms in disease or pharmacodynamics studies using MS data from longitudinal cohort studies. PMID:26317529

Multiple Independent Genetic Factors at NOS1AP Modulate the QT Interval in a Multi-Ethnic Population

PubMed Central

Arking, Dan E.; Khera, Amit; Xing, Chao; Kao, W. H. Linda; Post, Wendy; Boerwinkle, Eric; Chakravarti, Aravinda

2009-01-01

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6×10−5) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP × sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63×10−8), as well as the sex-interaction with rs16847548 (P = 8.68×10−6). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval. PMID:19180230

Assessment of Dietary Intake of Children with Chronic Kidney Disease

PubMed Central

Hui, W. F.; Betoko, Aisha; Savant, Jonathan D.; Abraham, Alison G.; Greenbaum, Larry A.; Warady, Bradley; Moxey-Mims, Marva M.; Furth, Susan L.

2017-01-01

Objective Our aim was to characterize the nutrient intake of children with chronic kidney disease (CKD) relative to recommended intake levels. Methods We conducted a cross-sectional study of dietary intake assessed by food frequency questionnaire (FFQ) in The North American Chronic Kidney Disease in Children (CKiD) prospective cohort study. Nutrient intake was analyzed to estimate the daily consumption levels of various nutrients and compared to national guidelines for intake. Results There were 658 FFQs available for analysis; 69.9% of respondents were boys, with a median age (Interquartile range [IQR]) of 11 years (8–15). Median daily sodium, potassium and phosphorus intake of the cohort was 3089 mg (2294–4243), 2384 mg (1804–3076) and 1206 mg (894–1612) respectively. Sodium and phosphorus consumptions were higher than recommended in all age groups. Caloric intake decreased with dropping glomerular filtration rate (p=0.003). Median daily caloric intakes were 1307 kcal in male children 2–3 years old, 1875 kcal in 4–8 year old, 1923 kcal in those 9–13 years old, and 2427 kcal in those 14–18 years old. Respective levels for girls were 1467 kcal, 1736 kcal, 1803 kcal, and 2281 kcal. Median protein intake exceeded recommended levels in all age groups, particularly among younger participants. Younger children were more likely than older children to exceed the recommended intakes for phosphorus (p<0.001) and the age-specific recommended caloric intake (p<0.001). Macronutrient distribution (carbohydrate: fat: protein) was consistent with recommendation. Conclusions Children in the CKiD cohort consumed more sodium, phosphorus, protein and calories than recommended. The gap between actual consumption and recommendations indicates a need for improved nutritional counseling and monitoring. PMID:27687620

Timing of food introduction and development of food sensitization in a prospective birth cohort.

PubMed

Tran, Maxwell M; Lefebvre, Diana L; Dai, David; Dharma, Christoffer; Subbarao, Padmaja; Lou, Wendy; Azad, Meghan B; Becker, Allan B; Mandhane, Piush J; Turvey, Stuart E; Sears, Malcolm R

2017-08-01

The effect of infant feeding practices on the development of food allergy remains controversial. We examined the relationship between timing and patterns of food introduction and sensitization to foods at age 1 year in the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study. Nutrition questionnaire data prospectively collected at age 3, 6, 12, 18, and 24 months were used to determine timing of introduction of cow's milk products, egg, and peanut. At age 1 year, infants underwent skin prick testing to cow's milk, egg white, and peanut. Logistic regression models were fitted to assess the impact of timing of food exposures on sensitization outcomes, and latent class analysis was used to study patterns of food introduction within the cohort. Among 2124 children with sufficient data, delaying introduction of cow's milk products, egg, and peanut beyond the first year of life significantly increased the odds of sensitization to that food (cow's milk adjOR 3.69, 95% CI 1.37-9.08; egg adjOR 1.89, 95% CI 1.25-2.80; peanut adjOR 1.76, 95% CI 1.07-3.01). Latent class analysis produced a three-class model: early, usual, and delayed introduction. A pattern of delayed introduction, characterized by avoidance of egg and peanut during the first year of life, increased the odds of sensitization to any of the three tested foods (adjOR 1.78, 95% CI 1.26-2.49). Avoidance of potentially allergenic foods during the first year of life significantly increased the odds of sensitization to the corresponding foods. © 2017 The Authors. Pediatric Allergy and Immunology Published by John Wiley & Sons Ltd.

Prevalence of simple and complex sacral perineural Tarlov cysts in a French cohort of adults and children.

PubMed

Kuhn, Félix P; Hammoud, Sonia; Lefèvre-Colau, Marie-Martine; Poiraudeau, Serge; Feydy, Antoine

2017-02-01

To determine the prevalence of simple and complex sacral perineural Tarlov cysts (TCs) in a cohort of children and adults. Retrospective observational epidemiological study assessing 1100 consecutive sacral magnetic resonance (MR) studies, including 100 children and adolescents. All patients underwent 1.5T MR imaging with T1 and T2 weighted image acquisitions in sagittal and axial planes. All perineural cysts affecting the sacral nerve roots S1-S4 were quantitatively and qualitatively assessed. Two hundred and sixty-three sacral TCs were found in 132 adult patients (13.2%), with a female predominance (68%). None was found in children. The prevalence of TCs increased with age. The average number of cysts per patient was 2.0±1.2 with a maximum of 6 cysts in a single patient. Most of the cysts (87.5%) showed a homogenous central fluid collection and a parietal course of the nerve fibers. Complex patterns were present in 33 cysts (12.5%) within which 28 cysts showed endocystic crossing of nerve fibers and 5 cysts contained internal septations. Seventy cysts (26.6%) eroded the adjacent bone and 13 cysts (4.9%) extended to the pelvis. The prevalence of sacral TCs in our cohort corresponded to 13%, with a female predominance. Interestingly no TCs were found in children or adolescents (<18 years). In relation to the non-negligible percentage of complex cysts with internal septations, or endocystic crossing of nerve fibers, pre-interventional characterization of sacral TCs might help to choose an appropriate procedure in the treatment of rare symptomatic variants. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

An Exploration of the Impact of Initial Timing of Physical Therapy on Safety and Outcomes After Concussion in Adolescents.

PubMed

Lennon, Anne; Hugentobler, Jason A; Sroka, Mary Claire; Nissen, Katharine S; Kurowski, Brad G; Gagnon, Isabelle; Quatman-Yates, Catherine C

2018-05-24

Physical therapy (PT) is a management strategy increasingly recognized to facilitate recovery after concussion. The purpose of this study was to investigate the safety and outcomes of multimodal impairment-based PT at varying time points after injury in youth diagnosed with concussion. Data were extracted retrospectively from medical records for patients who received PT for concussion-related impairments. Patient records were categorized into 3 cohorts on the basis of the timing of PT implementation: 0-20 days following injury (early intervention), 21 to 41 days following injury (middle intervention), and 42 or more days following injury (late intervention). The primary outcome measure was Post-Concussion Symptom Inventory score from the beginning to the end of the PT episode of care. Additional outcome measures included number of PT sessions, duration of PT episode of care (days), and occurrence of unplanned visits to a health care provider. A total of 120 patient records (mean age of 14.77 years) were analyzed. Thirty-three, 39, and 48 individuals were categorized into the early, middle, and late intervention cohorts, respectively. There were no significant differences between intervention cohorts with regard to symptom change on the Post-Concussion Symptom Inventory from the beginning to the end of the PT episode of care, unplanned health care visits, number of PT sessions, or duration of PT episode of care. Early initiation of PT may be safe and tolerable. Future prospective studies are needed to explore the efficacy of PT services administered early following injury to help characterize an optimal care plan for youth following concussion.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A210).