Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Cost-effectiveness of preventive case management for parents with a mental illness: A randomized controlled trial from three economic perspectives

Contains fulltext : 158917.pdf (publisher's version ) (Open Access)Background: The children of parents with a mental illness (COPMI) are at increased risk for developing costly psychiatric disorders because of multiple risk factors which threaten parenting quality and thereby child development. Preventive basic care management (PBCM) is an intervention aimed at reducing risk factors and addressing the needs of COPMI-families in different domains. The intervention may lead to financial consequences in the healthcare sector and in other sectors, also known as inter-sectoral costs and benefits (ICBs). The objective of this study was to assess the cost-effectiveness of PBCM from three perspectives: a narrow healthcare perspective, a social care perspective (including childcare costs) and a broad societal perspective (including all ICBs). Methods: Effects on parenting quality (as measured by the HOME) and costs during an 18-month period were studied in in a randomized controlled trial. Families received PBCM (n = 49) or care as usual (CAU) (n = 50). For all three perspectives, incremental cost-effectiveness ratios (ICERs) were calculated. Stochastic uncertainty in the data was dealt with using non-parametric bootstraps. Sensitivity analyses included calculating ICERs excluding cost outliers, and making an adjustment for baseline cost differences. Results: Parenting quality improved in the PBCM group and declined in the CAU group, and PBCM was shown to be more costly than CAU. ICERs differ from 461 Euros (healthcare perspective) to 215 Euros (social care perspective) to 175 Euros (societal perspective) per one point improvement on the HOME T-score. The results of the sensitivity analyses, based on complete cases and excluding cost outliers, support the finding that the ICER is lower when adopting a broader perspective. The subgroup analysis and the analysis with baseline adjustments resulted in higher ICERs. Conclusions: This study is the first economic evaluation of family-focused preventive basic care management for COPMI in psychiatric and family services. The effects of the chosen perspective on determining the cost-effectiveness of PBCM underscore the importance of economic studies of interdepartmental policies. Future studies focusing on the cost-effectiveness of programs like PBCM in other sites and studies with more power are encouraged as this may improve the quality of information used in supporting decision making. Trial registration: NTR2569, date of registration 2010-10-12.15 p

Diagnostic yield of muscle fibre conduction velocity in myopathies

Item does not contain fulltextWe prospectively assessed diagnostic yield of muscle fiber conduction velocity (MFCV) studies in patients with signs and symptoms suggestive of a myopathy. Results were analysed with respect to the final diagnosis, and compared to the reference standard, which was qualitative electromyography (EMG), turns-amplitude analysis (TAA), and muscle biopsy. We included 125 patients, in whom a myopathy was diagnosed in 71, and a neuromuscular disorder was excluded in 54. Sensitivity of MFCV for the presence of a myopathy was 84%, and specificity 83%. Diagnostic yield of MFCV was superior to EMG, TAA, and muscle biopsy in patients with metabolic myopathies, non-dystrophic myopathies, and channelopathies. We concluded that measurement of MFCV is a quantitative EMG technique with a high diagnostic yield. In certain myopathies, MFCV may be more informative than conventional EMG examination

Chronic progressive external ophthalmoplegia caused by an m.4267A > G mutation in the mitochondrial tRNAIle.

Contains fulltext : 52239.pdf (publisher's version ) (Closed access

Raising the Profile of Research Software

Research software is fundamental to contemporary research, yet it does not receive the recognition it rightfully deserves. This needs to change, particularly in the context of the discussions around open science and reproducibility. We argue that if open science is to truly lead towards better, more transparent, and reproducible research, then research software needs to be treated in equal footing to research data and publications at the policy level