Abstract

Abstract
The current availability of large volumes of health care data makes it a promising data source to new views on disease interaction. Most of the times, patients have multiple diseases instead of a single one (also known as multimorbidity), but the small size of most clinical research data makes it hard to impossible to investigate this issue. In this paper, we propose a latent-based approach to expand patient evolution in temporal electronic health records, which can be uninformative due to its very general events. We introduce the notion of clusters of hidden states allowing for an expanded understanding of the multiple dynamics that underlie events in such data. Clusters are defined as part of hidden Markov models learned from such data, where the number of hidden states is not known beforehand. We evaluate the proposed approach based on a large dataset from Dutch practices of patients that had events on comorbidities related to atherosclerosis. The discovered clusters are further correlated to medical-oriented outcomes in order to show the usefulness of the proposed method.

Abstract
The varied phenotypes of obstructive sleep apnea (OSA) poses critical challenges, resulting in missed or delayed diagnosis. In this work, we applied k-modes, aiming to identify groups of OSA patients, based on demographic, physical examination, clinical history, and comorbidities characterization variables (n=41) collected from 318 patients. Missing values were imputed with k-nearest neighbours (k-NN) and chi-square test was held. Thirteen variables were inserted in cluster analysis, resulting in three clusters. Cluster 1 were middle-aged men, while Cluster 3 were the oldest men and Cluster 2 mainly middle-aged women. Cluster 3 weighted the most, whereas Cluster 1 weighted the least. The same effect was described in increased neck circumference. The percentages of variables driving sleepiness, congestive heart failure, arrhythmias and pulmonary hypertension were very low (<20%) and OSA severity was more common in mild level. Our results suggest that it is possible to phenotype OSA patients in an objective way, as also, different (although not considered innovative) visualizations improve the recognition of this common sleep pathology.

Abstract
In pharmacovigilance, reported cases are considered suspected adverse drug reactions (ADR). Health authorities have thus adopted structured causality assessment methods, allowing the evaluation of the likelihood that a drug was the causal agent of an adverse reaction. The aim of this work was to develop and validate a new causality assessment support system used in a regional pharmacovigilance centre. A Bayesian network was developed, for which the structure was defined by experts while the parameters were learnt from 593 completely filled ADR reports evaluated by the Portuguese Northern Pharmacovigilance Centre medical expert between 2000 and 2012. Precision, recall and time to causality assessment (TTA) was evaluated, according to the WHO causality assessment guidelines, in a retrospective cohort of 466 reports (April-September 2014) and a prospective cohort of 1041 reports (January-December 2015). Additionally, a simplified assessment matrix was derived from the model, enabling its preliminary direct use by notifiers. Results show that the network was able to easily identify the higher levels of causality (recall above 80%), although struggling to assess reports with a lower level of causality. Nonetheless, the median (Q1:Q3) ITA was 4 (2:8) days using the network and 8 (5:14) days using global introspection, meaning the network allowed a faster time to assessment, which has a procedural deadline of 30 days, improving daily activities in the centre. The matrix expressed similar validity, allowing an immediate feedback to the notifiers, which may result in better future engagement of patients and health professionals in the pharmacovigilance system.

Abstract

Abstract
The literature on gait analysis in Vascular Parkinsonism (VaP), addressing issues such as variability, foot clearance patterns, and the effect of levodopa, is scarce. This study investigates whether spatiotemporal, foot clearance and stride-to-stride variability analysis can discriminate VaP, and responsiveness to levodopa. Fifteen healthy subjects, 15 Idiopathic Parkinson's Disease (IPD) patients and 15 VaP patients, were assessed in two phases: before (Off-state), and one hour after (On-state) the acute administration of a suprathreshold (1.5 times the usual) levodopa dose. Participants were asked to walk a 30-meter continuous course at a self-selected walking speed while wearing foot-worn inertial sensors. For each gait variable, mean, coefficient of variation (CV), and standard deviations SDI and SD2 obtained by Poincare analysis were calculated. General linear models (GLMs) were used to identify group differences. Patients were subject to neuropsychological evaluation (MoCA test) and Brain MRI. VaP patients presented lower mean stride velocity, stride length, lift-off and strike angle, and height of maximum toe (later swing) (p < .05), and higher %gait cycle in double support, with only the latter unresponsive to levodopa. VaP patients also presented higher CV, significantly reduced after levodopa. Yet, all VaP versus IPD differences lost significance when accounting for mean stride length as a covariate. In conclusion, VaP patients presented a unique gait with reduced degrees of foot clearance, probably correlated to vascular lesioning in dopaminergic/non-dopaminergic cortical and subcortical non-dopaminergic networks, still amenable to benefit from levodopa. The dependency of gait and foot clearance and variability deficits from stride length deserves future clarification.