Decreasing uptake of predictive testing for Huntington's disease in a German centre: 12 years' experience (1993-2004).
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ABSTRACT:
SUBMITTER: Bernhardt C
PROVIDER: S-EPMC2986171 | biostudies-other | 2009 Mar
REPOSITORIES: biostudies-other
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Project description:BackgroundWe aimed to investigate the association between preterm birth and body composition at 6, 18, and 30 years of age using data from three population-based birth cohort studies.MethodsGestational age (GA), defined by the date of the last menstrual period (categorized in ≤33, 34-36, and ≥ 37 weeks), was gathered in the first 24-h after delivery for all live births occurring in the city of Pelotas, Brazil, in 2004, 1993 and 1982. Body composition was assessed by air-displacement plethysmography. Outcomes included fat mass (FM, kg), percent FM (%FM), FM index (FMI, kg/m2), fat-free mass (FFM, kg); percent FFM (%FFM), FFM index (FFMI, kg/m2), body mass index (BMI, kg/m2 at 18 years in the 1993 cohort and 30 years in the 1982 cohort), and BMI Z-score (at 6 years in the 2004 cohort). We further explored the association of birth weight for GA with body composition indicators and BMI. Crude and adjusted linear regressions provided beta coefficients with 95% confidence intervals (95%CI).ResultsA total of 3036, 3027, and 3369 participants, respectively, from the 2004, 1993, and 1982 cohorts were analyzed. At 6 years, preterm boys (born at 34-36 weeks) presented lower adjusted mean of FM (β = - 0.80 kg, - 1.45;-0.16, p = 0.046), %FM (β = - 2.39%, - 3.90;-0.88, p = 0.008), FMI (β = - 0.70 kg/m2, - 1.13;-0.27, p = 0.004) as well as lower FFM (β = - 0.4 kg, - 0.77; - 0.12, p = 0.010) and FFMI (β = - 0.3 kg/m2, - 0.46;-0.10, p < 0.001), and BMI Z-score (β = - 0.69,; - 0.99;-0.40, p < 0.001); but higher %FFM (β = 2.4%, 0.87;-3.90, p = 0.008), when compared to boys born at term (≥37). At 30 years, FM (15.7 kg, 0.25;31.1, p = 0.102) was higher among males born at ≤33 weeks. No association was observed for females from the three cohorts and for 18-year-old males. The association of birth weight for GA with body composition and BMI was not significant in any cohort. At 6 years, SGA boys had lower FFMI than boys AGA.ConclusionsOur results suggest that preterm birth is associated with decreased body fat and fat-free mass in childhood but higher fat mass in adulthood. Nevertheless, results were only significant for males. SGA boys also showed lower FFMI.
| S-EPMC7871570 | biostudies-literature
Project description:BackgroundIt is well known in Huntington's disease that cytosine-adenine-guanine expansion and age at study entry are predictive of the timing of motor diagnosis. The goal of this study was to assess whether additional motor, imaging, cognitive, functional, psychiatric, and demographic variables measured at study entry increased the ability to predict the risk of motor diagnosis over 12 years.MethodsOne thousand seventy-eight Huntington's disease gene-expanded carriers (64% female) from the Neurobiological Predictors of Huntington's Disease study were followed up for up to 12 y (mean = 5, standard deviation = 3.3) covering 2002 to 2014. No one had a motor diagnosis at study entry, but 225 (21%) carriers prospectively received a motor diagnosis. Analysis was performed with random survival forests, which is a machine learning method for right-censored data.ResultsAdding 34 variables along with cytosine-adenine-guanine and age substantially increased predictive accuracy relative to cytosine-adenine-guanine and age alone. Adding six of the common motor and cognitive variables (total motor score, diagnostic confidence level, Symbol Digit Modalities Test, three Stroop tests) resulted in lower predictive accuracy than the full set, but still had twice the 5-y predictive accuracy than when using cytosine-adenine-guanine and age alone. Additional analysis suggested interactions and nonlinear effects that were characterized in a post hoc Cox regression model.ConclusionsMeasurement of clinical variables can substantially increase the accuracy of predicting motor diagnosis over and above cytosine-adenine-guanine and age (and their interaction). Estimated probabilities can be used to characterize progression level and aid in future studies' sample selection.
| S-EPMC4795466 | biostudies-literature
Project description:The inherited prion diseases (IPD) are a group of untreatable neurodegenerative diseases that segregate as autosomal dominant traits. Mutations in the prion protein gene (PRNP) were first found to be causal of IPD in 1989, before the molecular genetic characterisation of any other neurodegenerative disease. Predictive testing for IPD has subsequently been carried out at a single UK clinical and research centre for 22 years. We have analysed the uptake, consequences and factors influencing the decision for predictive testing over this period. In all, 104 predictive tests were done on individuals at 50% risk, compared with 135 positive diagnostic tests. Using genealogies from clinical records, we estimated that 23% of those at 50% risk have completed testing. There was no gender bias, and unsurprisingly, there was a slight excess of normal results because some patients were already partly through the risk period because of their age. An unexpectedly large number of patients developed symptoms shortly after predictive testing, suggesting that undisclosed early symptoms of disease may prompt some patients to come forward for predictive testing. Fifteen per cent of predictive tests were done >10 years after molecular diagnosis in a proband. A strong determinant of the timing of testing in these patients was a second diagnosis in the family. IPD may generate infectious prions that might be transmitted by surgical procedures; however, we found no evidence that public health information influenced decisions about predictive testing.
| S-EPMC4091984 | biostudies-literature
Project description:The point of departure for the present work is the observation that, in comparison with Anglo-American countries or the Netherlands, Germany was responsible for only a marginal number of international publications in the field of medical education research before 2004. Recent years, however, have seen an increase in the importance of medical education research in Germany. The objective of this article is to evaluate the extent to which this trend can be substantiated by increased German publishing activity since the year 2004 in international, English-language journals in the subject area of "medical education research".In the framework of a literature and content analysis, German-author articles from the years 2004 to 2013 in six international, English-language medical education research journals were evaluated. In order to obtain an overview of German research activity in this area, all project and original works with German first and last authors were identified and subjected to a more in-depth content analysis.In total, 10,055 articles were examined. The evaluation shows that between the years 2004 and 2013 179 articles (of which 145 are project or original works) by German authors were published in the journals examined. Fluctuations over the course of time were evidenced. The project and original works are primarily cross-sectional studies (27.8%) and randomised control studies (25.6%) on the subject of "teaching and learning methods" (43.6%).In comparison with the years 2004-2008, a significant rise can be seen in the number of publications by German education researchers in international journals since the year 2009.
| S-EPMC4580754 | biostudies-other
Project description:Background:This study examined the validity of the FitnessGram® criterion-reference cut-points for cardiorespiratory fitness (CRF) based on two samples of US adolescents (aged 12-15 years). This study also established the CRF cut-points for metabolically healthy weight status based on a recent national fitness survey for the purposes of cross-validating with pre-existing cut-points including FitnessGram. Methods:Two cross-sectional data from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) (n = 378) and 2012 NHANES National Youth Fitness Survey (NNYFS) (n = 451) were used. CRF (estimated V? O2max in mL/kg/min) was estimated from a submaximal exercise test. CRF categories based on FitnessGram cut-points, a clustered cardiometabolic risk factors score and weight status were used. A series of Receiver Operating Characteristic (ROC) curve analyses were conducted to identify age- and sex-specific CRF cut-points that were optimal for metabolically healthy weight status. Results:Based on FitnessGram cut-points, having high risk CRF, but not low risk CRF, was associated with high cardiometabolic risk (OR = 3.17, 95% CI = 1.14-8.79) and unhealthy weight status (OR = 5.81, 95% CI = 3.49-9.68). The optimal CRF cut-points for 12-13-year-olds and 14-15-year-olds were 40 and 43 mL/kg/min in males and 39 and 34 mL/kg/min in females, respectively. Compared to meeting new CRF cut-points, not meeting new CRF cut-points was associated with higher odds of showing high cardiometabolic risk (OR = 2.91, 95% CI = 1.47-5.77) and metabolically unhealthy weight status (OR = 4.47, 95% CI = 2.83-7.05). Conclusion:FitnessGram CRF cut-point itself has rarely been scrutinized in previous literature. Our findings provide partial support for FitnessGram based on two samples of US adolescents. CRF cut-points established in this study supports international criterion-referenced cut-points as well as FitnessGram cut-points only for males. FitnessGram should be continuously monitored and scrutinized using different samples.
| S-EPMC7248668 | biostudies-literature
Project description:Primary culture of marrow-derived mesenchymal cells vs marrow-derived MSCs with a prolonged life span vs MSCs with a prolonged life span after neuronal induction. Keywords: repeat sample
2004-12-28 | GSE2110 | GEO
Project description:This multi-centre UK study assesses the impact of predictive testing for breast and ovarian cancer predisposition genes (BRCA1/2) in the clinical context. In the year following predictive testing, 261 adults (59 male) from nine UK genetics centres participated; 91 gene mutation carriers and 170 noncarriers. Self-report questionnaires were completed at baseline (pre-genetic testing) and 1, 4 and 12 months following the genetic test result. Men were assessed for general mental health (by general health questionnaire (GHQ)) and women for general mental health, cancer-related worry, intrusive and avoidant thoughts, perception of risk and risk management behaviour. Main comparisons were between female carriers and noncarriers on all measures and men and women for general mental health. Female noncarriers benefited psychologically, with significant reductions in cancer-related worry following testing (P<0.001). However, younger female carriers (<50 years) showed a rise in cancer-related worry 1 month post-testing (P<0.05). This returned to pre-testing baseline levels 12 months later, but worry remained significantly higher than noncarriers throughout (P<0.01). There were no significant differences in GHQ scores between males and females (both carriers and noncarriers) at any time point. Female carriers engaged in significantly more risk management strategies than noncarriers in the year following testing (e.g. mammograms; 92% carriers vs 30% noncarriers). In the 12 months post-testing, 28% carriers had bilateral risk-reducing mastectomy and 31% oophorectomy. Oophorectomy was confined to older (mean 41 yrs) women who already had children. However, worry about cancer was not assuaged by surgery following genetic testing, and this requires further investigation. In all, 20% of female carriers reported insurance problems. The data show persistent worry in younger female gene carriers and confirm changes in risk management consistent with carrier status. Men were not adversely affected by genetic testing in terms of their general mental health.
| S-EPMC2410052 | biostudies-other
Project description:BackgroundPost-concussion symptoms (PCS) are a common consequence of pediatric traumatic brain injury (pTBI). They include cognitive, emotional, and physical disturbances. To address the lack of age-adapted instruments assessing PCS after pTBI, this study examines the psychometric properties of the German 17-item post-TBI version of the Postconcussion Symptom Inventory (PCSI-SR8) in children aged 8-12 years. The study also aims to establish reference values based on data from a pediatric general population sample to better estimate the prevalence and clinical relevance of PCS after pTBI in clinical and research settings.MethodsA total of 132 children aged 8-12 years from a post-acute TBI sample and 1,047 from a general population sample were included in the analyses. The questionnaire was translated from English into German and linguistically validated using forward and backward translation and cognitive debriefing to ensure comprehensibility of the developed version. Reliability and validity were examined; descriptive comparisons were made with the results of the English study. Measurement invariance (MI) analyses between TBI and general population samples were conducted prior to establishing reference values. Factors contributing to the total and scale scores of the PCSI-SR8 were identified using regression analyses. Reference values were calculated using percentiles.ResultsMost children (TBI: 83%; general population: 79%) rated at least one symptom as "a little" bothersome. The German PCSI-SR8 met the psychometric assumptions in both samples and was comparable to the English version. The four-factor structure comprising physical, emotional, cognitive, and fatigue symptoms could be replicated. The MI assumption was retained. Therefore, reference values could be provided to determine the symptom burden of patients in relation to a comparable general population. Clinical relevance of reported symptoms is indicated by a score of 8, which is one standard deviation above the mean of the general population sample.ConclusionThe German version of the PCSI-SR8 is suitable for assessment of PCS after pTBI. The reference values allow for a more comprehensive evaluation of PCS following pTBI. Future research should focus on validation of the PCSI-SR8 in more acute phases of TBI, psychometric examination of the pre-post version, and child-proxy comparisons.
| S-EPMC10693295 | biostudies-literature
Project description:BackgroundThere are an increasing number of reports on time trends in child and adolescent psychological problems but none from low- and middle-income countries, and very few covering the preschool period. The aim was to investigate changes in preschool behavioral/emotional problems in two birth cohorts from a middle-income country born 11 years apart.MethodsWe analyzed data from the 1993 and 2004 Pelotas birth cohort studies from Brazil. A subsample of 4-year olds from the 1993 cohort (634) and all 4-year olds from the 2004 cohort (3750) were assessed for behavioral/emotional problems through maternal report using the Child Behavior Checklist (CBCL). Response rates in these two population-based cohorts were above 90%.ResultsWe found a significant increase in CBCL total problems, internalizing and externalizing mean scores over the 11-year period. For 1993 and 2004 Pelotas cohorts, respectively, CBCL mean values (SE) total problems scores were 27.9 (0.8) and 34.7 (0.3); for internalizing scores, 5.7 (0.2) and 6.3 (0.1) and for externalizing scores, 12.4 (0.4) and 15.5 (0.1). After adjusting for confounding variables, the largest increase from 1993 to 2004 was identified in the aggressive behavior syndrome score (Cohen's d = .50), followed by the externalizing problem score (Cohen's d = .40) and CBCL total problem score (Cohen's d = .36), respectively. The rise in child psychological problems was more marked in children from families with fewer assets and with less educated mothers.ConclusionsOur findings provide evidence for a substantial increase in preschool behavioral problems among children in Brazil over an 11-year period.
| S-EPMC4263231 | biostudies-literature
Project description:BackgroundElimination of mother-to-child transmission (MTCT) of HIV by 2020 is a goal of the World Health Organization (WHO) action plan for the European Region. However, data to monitor progress towards MTCT elimination are not readily available in Germany.AimWe aimed to estimate the number of pregnant women with HIV and MTCT rates in Germany.MethodsWe triangulated retrospectively obtained data from: (i) healthcare reimbursement for HIV screening tests, (ii) a statutory health insurance subsample of prevalent and incident HIV diagnoses among pregnant women, (iii) a mathematical model of the German HIV epidemic with number, region of origin and risk factors for women of childbearing age, and (iv) the statutory anonymous HIV registry on children infected through HIV MTCT.ResultsThe number of women aged 15-49 years with HIV increased from ca 6,000 in 1993 to ca 11,000 in 2016. Risk of injecting drug use (IDU) declined from 65% in 1993 to 16% in 2016. The annual proportion of women living with HIV giving live birth increased from a mean of 1.9% during 1993 to 1998 to 4.9% in 2011 to 2015. HIV screening rates during pregnancy increased from ca 50% in 2001 to ca 90% in 2016. The HIV MTCT rate dropped from 6.8% in 2001 to 1.1% in 2016.ConclusionsThe population of women living with HIV in Germany shifted from predominantly IDU-associated infections to predominantly sexually acquired infections, while fertility rates more than doubled. MTCT rates dropped, mainly because of improved detection and management of HIV in pregnancy.
| S-EPMC6891947 | biostudies-literature