Evaluation of smartphone-based testing to generate exploratory outcome measures in a phase 1 Parkinson's disease clinical trial

Ubiquitous digital technologies such as smartphone sensors promise to fundamentally change biomedical research and treatment monitoring in neurological diseases such as PD, creating a new domain of digital biomarkers.; The present study assessed the feasibility, reliability, and validity of smartphone-based digital biomarkers of PD in a clinical trial setting.; During a 6-month, phase 1b clinical trial with 44 Parkinson participants, and an independent, 45-day study in 35 age-matched healthy controls, participants completed six daily motor active tests (sustained phonation, rest tremor, postural tremor, finger-tapping, balance, and gait), then carried the smartphone during the day (passive monitoring), enabling assessment of, for example, time spent walking and sit-to-stand transitions by gyroscopic and accelerometer data.; Adherence was acceptable: Patients completed active testing on average 3.5 of 7 times/week. Sensor-based features showed moderate-to-excellent test-retest reliability (average intraclass correlation coefficient = 0.84). All active and passive features significantly differentiated PD from controls with P < 0.005. All active test features except sustained phonation were significantly related to corresponding International Parkinson and Movement Disorder Society-Sponsored UPRDS clinical severity ratings. On passive monitoring, time spent walking had a significant (P = 0.005) relationship with average postural instability and gait disturbance scores. Of note, for all smartphone active and passive features except postural tremor, the monitoring procedure detected abnormalities even in those Parkinson participants scored as having no signs in the corresponding International Parkinson and Movement Disorder Society-Sponsored UPRDS items at the site visit.; These findings demonstrate the feasibility of smartphone-based digital biomarkers and indicate that smartphone-sensor technologies provide reliable, valid, clinically meaningful, and highly sensitive phenotypic data in Parkinson's disease. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

The role of whole genome sequencing in antimicrobial susceptibility testing of bacteria:report from the EUCAST Subcommittee

Whole genome sequencing (WGS) offers the potential to predict antimicrobial susceptibility from a single assay. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) established a subcommittee to review the current development status of WGS for bacterial antimicrobial susceptibility testing (AST).The published evidence for using WGS as a tool to infer antimicrobial susceptibility accurately is currently either poor or non-existent and the evidence/knowledge base requires significant expansion. The primary comparators for assessing genotypic-phenotypic concordance from WGS data should be changed to epidemiological cut-off values (ECOFFs) in order to improve differentiation of wild type from non-wild type isolates (harbouring an acquired resistance). Clinical breakpoints should be a secondary comparator. This assessment will reveal whether genetic predictions could also be used to guide clinical decision making. Internationally agreed principles and quality control (QC) metrics will facilitate early harmonization of analytical approaches and interpretative criteria for WGS-based predictive AST. Only datasets that pass agreed QC metrics should be used in AST predictions. Minimum performance standards should exist and comparative accuracies across different WGS laboratories and processes should be measured. In order to facilitate comparisons, a single public database of all known resistance loci should be established, regularly updated and strictly curated using minimum standards for the inclusion of resistance loci.For most bacterial species the major limitations to widespread adoption for WGS-based AST in clinical labs remain the current high-cost and limited speed of inferring antimicrobial susceptibility from WGS data as well as the dependency on prior culture since analysis directly on specimens remains challenging. For most bacterial species there is currently insufficient evidence to support the use of WGS-inferred AST to guide clinical decision making. WGS-AST should be a funding priority if it is to become a rival to phenotypic AST. This report will be updated as the available evidence increases.</p

Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial.

A randomized, double-blind, placebo-controlled, 52-week study (no. NCT03068468) evaluated gosuranemab, an anti-tau monoclonal antibody, in the treatment of progressive supranuclear palsy (PSP). In total, 486 participants dosed were assigned to either gosuranemab (n = 321) or placebo (n = 165). Efficacy was not demonstrated on adjusted mean change of PSP Rating Scale score at week 52 between gosuranemab and placebo (10.4 versus 10.6, P = 0.85, primary endpoint), or at secondary endpoints, resulting in discontinuation of the open-label, long-term extension. Unbound N-terminal tau in cerebrospinal fluid decreased by 98% with gosuranemab and increased by 11% with placebo (P &lt; 0.0001). Incidences of adverse events and deaths were similar between groups. This well-powered study suggests that N-terminal tau neutralization does not translate into clinical efficacy

Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial.

A randomized, double-blind, placebo-controlled, 52-week study (no. NCT03068468) evaluated gosuranemab, an anti-tau monoclonal antibody, in the treatment of progressive supranuclear palsy (PSP). In total, 486 participants dosed were assigned to either gosuranemab (n = 321) or placebo (n = 165). Efficacy was not demonstrated on adjusted mean change of PSP Rating Scale score at week 52 between gosuranemab and placebo (10.4 versus 10.6, P = 0.85, primary endpoint), or at secondary endpoints, resulting in discontinuation of the open-label, long-term extension. Unbound N-terminal tau in cerebrospinal fluid decreased by 98% with gosuranemab and increased by 11% with placebo (P &lt; 0.0001). Incidences of adverse events and deaths were similar between groups. This well-powered study suggests that N-terminal tau neutralization does not translate into clinical efficacy