Prothrombin 20210A mutation: a mild risk factor for venous thromboembolism but not for arterial thrombotic disease and pregnancy-related complications in a family study

BACKGROUND: The prothrombin 20210A mutation has been associated with an increased risk of venous thromboembolism (VTE). Its relationship with arterial disease and pregnancy-related complications is, however, still uncertain. The aim of this study was to estimate the incidences of first venous and arterial thrombotic events and pregnancy-related complications in relatives of patients with the mutation. METHODS: After clinical classification, the presence of the mutation was determined in first-degree relatives of consecutive patients with the mutation and a history of VTE or premature atherosclerosis. Relatives with and without the mutation were compared. RESULTS: Of all relatives, 204 (50%) were heterozygous, 5 were homozygous, and 198 had a normal genotype. The annual incidence of a first episode of VTE was 0.35% and 0.18% in carriers and noncarriers, respectively (odds ratio [OR], 1.9; 95% confidence interval [CI], 0.9-4.1); the annual incidence of a first arterial thrombosis was 0.22% and 0.15% in carriers and noncarriers, respectively (OR, 2.3; 95% CI, 0.8-6.3). The annual incidence of a first myocardial infarction was 0.14% (95% CI, 0.05%-0.23%) and 0.05% (0.01%-0.14%) in carriers and noncarriers, respectively (OR, 4.7; 95% CI, 1.0-22.5; P =.06). In particular, homozygous carriers were at increased risk of VTE (OR, 6.0; 95% CI, 1.3-27.2), whereas a history of VTE in the proband influenced the risk of VTE in the relatives. Women with the mutation did not experience significantly more pregnancy-related complications than their relatives with a normal genotype. CONCLUSIONS: The prothrombin mutation is a mild risk factor for VTE within families of carriers but does not seem to play an important role in arterial thrombotic disease, with the exception of myocardial infarction, or in pregnancy-related complications.     

Task-related motivation and academic achievement in children and adolescents with ADHD

European Child & Adolescent Psychiatry - Academic impairment in individuals with attention-deficit/hyperactivity disorder (ADHD) is in part due to reduced motivation for academic tasks, which...     

Assessing the predictive ability of the Suicide Crisis Inventory for near‐term suicidal behavior using machine learning approaches

ObjectiveThis study explores the prediction of near‐term suicidal behavior using machine learning (ML) analyses of the Suicide Crisis Inventory (SCI), which measures the Suicide Crisis Syndrome, a presuicidal mental state.MethodsSCI data were collected from high‐risk psychiatric inpatients (N = 591) grouped based on their short‐term suicidal behavior, that is, those who attempted suicide between intake and 1‐month follow‐up dates (N = 20) and those who did not (N = 571). Data were analyzed using three predictive algorithms (logistic regression, random forest, and gradient boosting) and three sampling approaches (split sample, Synthetic minority oversampling technique, and enhanced bootstrap).ResultsThe enhanced bootstrap approach considerably outperformed the other sampling approaches, with random forest (98.0% precision; 33.9% recall; 71.0% Area under the precision‐recall curve [AUPRC]; and 87.8% Area under the receiver operating characteristic [AUROC]) and gradient boosting (94.0% precision; 48.9% recall; 70.5% AUPRC; and 89.4% AUROC) algorithms performing best in predicting positive cases of near‐term suicidal behavior using this dataset.ConclusionsML can be useful in analyzing data from psychometric scales, such as the SCI, and for predicting near‐term suicidal behavior. However, in cases such as the current analysis where the data are highly imbalanced, the optimal method of measuring performance must be carefully considered and selected.     

A Post‐Hoc Comparison of the Utility of Sanger Sequencing and Exome Sequencing for the Diagnosis of Heterogeneous Diseases

The advent of massive parallel sequencing is rapidly changing the strategies employed for the genetic diagnosis and research of rare diseases that involve a large number of genes. So far it is not clear whether these approaches perform significantly better than conventional single gene testing as requested by clinicians. The current yield of this traditional diagnostic approach depends on a complex of factors that include gene‐specific phenotype traits, and the relative frequency of the involvement of specific genes. To gauge the impact of the paradigm shift that is occurring in molecular diagnostics, we assessed traditional Sanger‐based sequencing (in 2011) and exome sequencing followed by targeted bioinformatics analysis (in 2012) for five different conditions that are highly heterogeneous, and for which our center provides molecular diagnosis. We find that exome sequencing has a much higher diagnostic yield than Sanger sequencing for deafness, blindness, mitochondrial disease, and movement disorders. For microsatellite‐stable colorectal cancer, this was low under both strategies. Even if all genes that could have been ordered by physicians had been tested, the larger number of genes captured by the exome would still have led to a clearly superior diagnostic yield at a fraction of the cost.     

Low testosterone levels and decline in physical performance and muscle strength in older men: findings from two prospective cohort studies

Objective Progressive declines in serum levels of testosterone parallel the decline in physical performance and muscle strength in ageing men, although findings are not conclusive. We examined whether levels of testosterone were associated with 3‐year decline in physical performance and muscle strength in older men. Design Longitudinal data were available for 486 men (mean age 74·9 years, SD 6·4) from the Longitudinal Ageing Study Amsterdam (LASA) and 1071 well‐functioning men (mean age 73·7 years, SD 2·8) from the Health, Ageing and Body Composition (Health ABC) study. Measurements Three‐year change in physical performance score and grip strength according to categories of total testosterone (TT) and free testosterone (FT) levels. Results The mean 3‐year change in physical performance was –1·1 (SD 2·7, –13·6%) in LASA and –0·3 (SD 1·5, –2·9%) in Health ABC. The mean 3‐year change in grip strength was –9·7 kg (SD 12·2, –13·2%) in LASA and –4·4 kg (SD 11·4,–5·8%) in Health ABC. Low levels of TT were not associated with decline in physical performance or with decline in muscle strength [e.g. mean change in physical performance –1·09 (SD 0·26) in the lowest quartile (Q1) and –0·88 (0·24) in the highest quartile (Q4) of total testosterone in LASA, and –0·26 (0·07) vs.–0·36 (0·11) in Health ABC]. Similar results were found for FT. Conclusions Low levels of TT and FT were neither associated with 3‐year decline in physical performance nor with 3‐year decline in muscle strength in two independent samples of older men.     

Characterization of mutations in ATP8B1 associated with hereditary cholestasis

Progressive familial intrahepatic cholestasis (PFIC) and benign recurrent intrahepatic cholestasis (BRIC) are clinically distinct hereditary disorders. PFIC patients suffer from chronic cholestasis and develop liver fibrosis. BRIC patients experience intermittent attacks of cholestasis that resolve spontaneously. Mutations in ATP8B1 (previously FIC1) may result in PFIC or BRIC. We report the genomic organization of ATP8B1 and mutation analyses of 180 families with PFIC or BRIC that identified 54 distinct disease mutations, including 10 mutations predicted to disrupt splicing, 6 nonsense mutations, 11 small insertion or deletion mutations predicted to induce frameshifts, 1 large genomic deletion, 2 small inframe deletions, and 24 missense mutations. Most mutations are rare, occurring in 1-3 families, or are limited to specific populations. Many patients are compound heterozygous for 2 mutations. Mutation type or location correlates overall with clinical severity: missense mutations are more common in BRIC (58% vs. 38% in PFIC), while nonsense, frameshifting, and large deletion mutations are more common in PFIC (41% vs. 16% in BRIC). Some mutations, however, lead to a wide range of phenotypes, from PFIC to BRIC or even no clinical disease. ATP8B1 mutations were detected in 30% and 41%, respectively, of the PFIC and BRIC patients screened.     

Adherence to HIV and TB Care and Treatment,the Role of Food Security and Nutrition

Food security and nutrition play an important role in HIV and TB care and treatment, including for improving treatment outcomes, adherence and uptake of HIV and TB care. This AIDS and behaviour supplement on “Adherence to HIV and TB care and treatment, the role of food security and nutrition” provides an overview of the current evidence and knowledge about the barriers to uptake and retention in HIV and TB treatment and care and on whether and how food and nutrition assistance can help overcome these barriers. It contains nine papers on three topic areas discussing: (a) adherence and food and nutrition security in context of HIV and TB, their definitions, measurement tools and the current situation; (b) food and nutrition insecurity as barriers to uptake and retention; and (c) food and nutrition assistance to increase uptake and retention in care and treatment. Future interventions in the areas of food security, nutrition and social protection for increasing access and adherence should be from an HIV sensitive lens, linking the continuum of care with health systems, food systems and the community, complementing existing platforms through partnerships and integrated services.     

The Enabling Effect of Food Assistance in Improving Adherence and/or Treatment Completion for Antiretroviral Therapy and Tuberculosis Treatment: A Literature Review

Socioeconomic costs of HIV and TB and the difficulty of maintaining optimal treatment are well documented. Social protection measures such as food assistance may be required to offset some of the treatment related costs as well as to ensure food security and maintain good health of the affected individual and household. Programmes have started placing greater emphasis on treatment adherence and are looking for proven interventions that can optimize it. This paper looks at the effect of food assistance for enabling treatment adherence and reviews studies that used food assistance to promote adherence. Eight of ten studies found that provision of food can improve adherence and/or treatment completion for HIV care and treatment, ART and TB-DOTS. This indicates that food provision is not only a biological, but also a behavioural intervention, and underscores that unresolved food insecurity can be an impediment to treatment adherence and consequently to good treatment outcomes.