Feasibility of preconception screening for thalassaemia in Indonesia: exploring the opinion of Javanese mothers

Background. Thalassaemia has become a major public health issue in Indonesia. It has been estimated that up to 10% of the population carries a gene associated with beta-thalassaemia. Currently, there is no formal recommendation for thalassaemia screening. This study aimed to explore awareness of thalassaemia, and to explore attitudes regarding carrier testing among Javanese mothers. Methods. A quantitative questionnaire, designed using constructs of the Theory of Planned Behaviour, was applied cross-sectionally. Results. Out of 191 mothers who were invited, 180 agreed to participate (RR 94%), of whom 74 had a child affected with thalassaemia. Both attitudes towards receiving information about thalassaemia, and attitudes towards carrier testing were very positive. Awareness of thalassaemia was poor. Mothers, both those with and without an affected child, had barely heard of thalassaemia, nor of carrier testing. However, all mothers, including those with an affected child expressed high levels of interest in carrier testing. Respondents did not perceive that they had any control over carrier testing, and feared stigmatization and being discriminated against if their carrier status was identified. Attitudes towards carrier testing explained 23% of future reproductive intentions, in addition to perceived stigmatization, education level and ‘mother’s age’ (R2 0.44; p 0.001). Conclusion. Responding mothers expressed high levels of interest in receiving information on both thalassaemia and carrier testing. The less educated and the more deprived they were, the keener they were to receive this information. Overall, awareness of thalassaemia was low. Even mothers with affected children seemed unaware of the inheritance pattern and the recurrent risk of having an affected child in a subsequent pregnancy, showing the need for genetic counselling in Indonesia. It is therefore recommended not only to raise awareness about thalassaemia, but to improve the education of healthcare professionals as well. Keywords: thalassaemia; carrier screening; Javanese mothers; genetic awareness; Theory of Planned Behaviour (TpB); awareness; Indonesi

Testing the Children: Do Non-Genetic Health-Care Providers Differ in Their Decision to Advise Genetic Presymptomatic Testing on Minors? A Cross-Sectional Study in Five Countries in the European Union

BACKGROUND: Within Europe many guidelines exist regarding the genetic testing of minors. Predictive and presymptomatic genetic testing of minors is recommended for disorders for which medical intervention/preventive measures exist, and for which early detection improves future medical health. AIM: This study, which is part of the larger 5th EU-framework "genetic education" (GenEd) study, aimed to evaluate the self-reported responses of nongenetic health-care providers in five different EU countries (Germany, France, Sweden, the United Kingdom, and the Netherlands) when confronted with a parent requesting presymptomatic testing on a minor child for a treatable disease. METHODS: A cross-sectional study design using postal, structured scenario-based questionnaires that were sent to 8129 general practitioners (GPs) and pediatricians, between July 2004 and October 2004, addressing self-reported management of a genetic case for which early medical intervention during childhood is beneficial, involving a minor. RESULTS: Most practitioners agreed on testing the oldest child, aged 12 years (81.5% for GPs and 87.2% for pediatricians), and not testing the youngest child, aged 6 months (72.6% for GPs and 61.3% for pediatricians). After multivariate adjustment there were statistical differences between countries in recommending a genetic test for the child at the age of 8 years. Pediatricians in France (50%) and Germany (58%) would recommend a test, whereas in the United Kingdom (22%), Sweden (30%), and the Netherlands (32%) they would not. CONCLUSION: Even though presymptomatic genetic testing in minors is recommended for disorders for which medical intervention exists, EU physicians are uncertain at what age starting to do so in young children

Outcomes after Complicated and Uncomplicated Mild Traumatic Brain Injury at Three- and Six-Months Post-Injury: Results from the CENTER-TBI Study

The objective of this study was to provide a comprehensive examination of the relation of complicated and uncomplicated mild traumatic brain injury (mTBI) with multidimensional outcomes at three- and six-months after TBI. We analyzed data from the Collaborative European NeuroTrauma Effectiveness Research (CENTER-TBI) research project. Patients after mTBI (Glasgow Coma scale (GCS) score of 13–15) enrolled in the study were differentiated into two groups based on computed tomography (CT) findings: complicated mTBI (presence of any traumatic intracranial injury on first CT) and uncomplicated mTBI (absence of any traumatic intracranial injury on first CT). Multidimensional outcomes were assessed using seven instruments measuring generic and disease-specific health-related quality of life (HRQoL) (SF-36 and QOLIBRI), functional outcome (GOSE), and psycho-social domains including symptoms of post-traumatic stress disorder (PTSD) (PCL-5), depression (PHQ-9), and anxiety (GAD-7). Data were analyzed using a multivariate repeated measures approach (MANOVA-RM), which inspected mTBI groups at three- and six-months post injury. Patients after complicated mTBI had significantly lower GOSE scores, reported lower physical and mental component summary scores based on the SF-36 version 2, and showed significantly lower HRQoL measured by QOLIBRI compared to those after uncomplicated mTBI. There was no difference between mTBI groups when looking at psychological outcomes, however, a slight improvement in PTSD symptoms and depression was observed for the entire sample from three to six months. Patients after complicated mTBI reported lower generic and disease specific HRQoL and worse functional outcome compared to individuals after uncomplicated mTBI at three and six months. Both groups showed a tendency to improve from three to six months after TBI. The complicated mTBI group included more patients with an impaired long-term outcome than the uncomplicated group. Nevertheless, patients, clinicians, researchers, and decisions-makers in health care should take account of the short and long-term impact on outcome for patients after both uncomplicated and complicated mTBI

Raising awareness of carrier testing for hereditary haemoglobinopathies in high-risk ethnic groups in the Netherlands: a pilot study among the general public and primary care providers

0.05). 191 surveys were collected from general practitioners or midwives. Their attitude towards the education programme for high-risk ethnic groups was positive, yet they did not show strong intention to effectuate carrier testing of their patients on the basis of ethnicity. The main factor which explained their (lack of) intention was social norm, i.e. their perception of negative peer opinion (41% variance explained). The majority of primary health care providers felt that policy change was unnecessary. CONCLUSION: The "infotainment" programme may have a positive effect on people from high-risk groups, but informed general practitioners and midwives were reluctant to facilitate their patients' getting tested. Additional initiatives are needed to motivate primary care providers to facilitate haemoglobinopathy carrier testing for their patients from high-risk background

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Reference Values and Psychometric Properties of the Quality of Life After Traumatic Brain Injury: Overall Scale in Italy, the Netherlands, and the United Kingdom

Objectives: The Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS) is a short screening instrument for assessing disease-specific health-related quality of life (HRQoL) after traumatic brain injury. To date, no reference values are available for the QOLIBRI-OS in general populations. Thus, this study aimed to establish reference values for the QOLIBRI-OS in general population samples from Italy, the Netherlands, and the United Kingdom. Methods: Data were collected using an online survey. The total sample comprised 11759 participants, consisting of 3549 Italian, 3564 Dutch, and 4646 British subjects. In this sample, 49% of the total sample did not report any health complaints, whereas 51% had at least 1 chronic health condition. Reference values were deduced for the QOLIBRI-OS for health-condition–related samples and total general population samples per country. To ensure the comparability of these values, measurement invariance was assessed using a multigroup confirmatory factor analysis. Covariates characterizing the reference values were selected with the help of regression analyses. Results: The confirmatory factor analysis confirmed that the QOLIBRI-OS scores measured the same traumatic brain injury–specific HRQoL construct across the 3 countries. Healthy individuals reported significantly higher HRQoL than individuals with at least 1 chronic health condition. Older age and higher education levels were significantly associated with higher HRQoL. Conclusions: Because the reference values displayed differences in terms of age and education level across the 3 countries, we recommend using country-specific reference values stratified by sociodemographic and health status in research and clinical practice

Reference Values and Psychometric Properties of the Quality of Life After Traumatic Brain Injury-Overall Scale in Italy, The Netherlands, and the United Kingdom

OBJECTIVES: The Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS) is a short screening instrument for assessing disease-specific health-related quality of life (HRQoL) after traumatic brain injury. To date, no reference values are available for the QOLIBRI-OS in general populations. Thus, this study aimed to establish reference values for the QOLIBRI-OS in general population samples from Italy, The Netherlands, and the United Kingdom. METHODS: Data were collected using an online survey. The total sample comprised 11759 participants, consisting of 3549 Italian, 3564 Dutch, and 4646 British subjects. In this sample, 49% of the total sample did not report any health complaints, whereas 51% had at least 1 chronic health condition. Reference values were deduced for the QOLIBRI-OS for health-condition-related samples and total general population samples per country. To ensure the comparability of these values, measurement invariance was assessed using a multigroup confirmatory factor analysis. Covariates characterizing the reference values were selected with the help of regression analyses. RESULTS: The confirmatory factor analysis confirmed that the QOLIBRI-OS scores measured the same traumatic brain injury-specific HRQoL construct across the 3 countries. Healthy individuals reported significantly higher HRQoL than individuals with at least 1 chronic health condition. Older age and higher education levels were significantly associated with higher HRQoL. CONCLUSIONS: Because the reference values displayed differences in terms of age and education level across the 3 countries, we recommend using country-specific reference values stratified by sociodemographic and health status in research and clinical practice