Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease.

Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression.

Trial of Prasinezumab in Early-Stage Parkinson's Disease.

Background: Aggregated α-synuclein plays an important role in the pathogenesis of Parkinson's disease. The monoclonal antibody prasinezumab, directed at aggregated α-synuclein, is being studied for its effect on Parkinson's disease.

Methods: In this phase 2 trial, we randomly assigned participants with early-stage Parkinson's disease in a 1:1:1 ratio to receive intravenous placebo or prasinezumab at a dose of 1500 mg or 4500 mg every 4 weeks for 52 weeks.

Reliability and validity of the Roche PD Mobile Application for remote monitoring of early Parkinson's disease.

Digital health technologies enable remote and therefore frequent measurement of motor signs, potentially providing reliable and valid estimates of motor sign severity and progression in Parkinson's disease (PD). The Roche PD Mobile Application v2 was developed to measure bradykinesia, bradyphrenia and speech, tremor, gait and balance. It comprises 10 smartphone active tests (with ½ tests administered daily), as well as daily passive monitoring via a smartphone and smartwatch.

Hoehn and Yahr Stage and Striatal Dat-SPECT Uptake Are Predictors of Parkinson's Disease Motor Progression.

Currently, no treatments available for Parkinson's disease (PD) can slow PD progression. At the early stage of the disease, only a subset of individuals with PD progress quickly, while the majority have a slowly progressive form of the disease. In developing treatments that aim to slow PD progression, clinical trials aim to include individuals who are likely to progress faster, such that a treatment effect, if one exists, can be identified easier and earlier.

Self-Report versus Clinician Examination in Early Parkinson's Disease.

Background: Evaluating the discrepancies between patient-reported measures and clinician examination has implications for formulating individual treatment regimens.

Objective: This study investigated the association between health outcomes and level of self-reported motor-related function impairment relative to clinician-examined motor signs.

Methods: Recently diagnosed PD patients were evaluated using the Parkinson's Progression Marker Initiative (PPMI, N = 420) and the PASADENA phase II clinical trial (N = 316).

A Phase II Study to Evaluate the Safety and Efficacy of Prasinezumab in Early Parkinson's Disease (PASADENA): Rationale, Design, and Baseline Data.

Currently available treatments for Parkinson's disease (PD) do not slow clinical progression nor target alpha-synuclein, a key protein associated with the disease. The study objective was to evaluate the efficacy and safety of prasinezumab, a humanized monoclonal antibody that binds aggregated alpha-synuclein, in individuals with early PD. The PASADENA study is a multicenter, randomized, double-blind, placebo-controlled treatment study.

Testing for Implicit Gender Bias among Plastic Surgeons.

Unlabelled: The aim of this study was to examine for the presence of implicit bias within the field of plastic surgery using a gender-specific Implicit Association Test (IAT), specifically looking at gender and career stereotypes.

Methods: A Gender-Career/Family Implicit Association Test was developed and distributed to the international plastic surgery community. Mean scores were calculated.

The perils of dressings: a cautionary tale of ischaemia.

A cohort of patients presented to Queen Victoria Hospital, UK, with iatrogenic toe ischaemia following application of a different, newly available post-procedure dressing with different properties to those usually used. This resulted in ischaemia with extensive skin and soft tissue damage, requiring debridement surgery and, in some cases, skin grafting. We aim to highlight the risk of morbidity from dressing application to the digits.

Longitudinal Analysis of Multiple Neurotransmitter Metabolites in Cerebrospinal Fluid in Early Parkinson's Disease.

Background: Cerebrospinal fluid (CSF) levels of monoamine metabolites may represent biomarkers of Parkinson's disease (PD).

Objective: The aim of this study was quantification of multiple metabolites in CSF from PD versus healthy control subjects (HCs), including longitudinal analysis.

Methods: Absolute levels of multiple monoamine metabolites in CSF were quantified by liquid chromatography coupled with tandem mass spectrometry from 161 individuals with early PD and 115 HCs from the Parkinson's Progression Marker Initiative and de novo PD (DeNoPA) studies.

Safety and feasibility of using acellular sterile filtered amniotic fluid as a treatment for patients with COVID-19: protocol for a randomised, double-blinded, placebo-controlled clinical trial.

Introduction: Human amniotic fluid (hAF) has been shown to reduce inflammation in multiple experimental models. hAF has previously been approved by the US Food and Drug Administration (FDA) as a human cellular and tissue product for tissue injury for human administration, and used safely in thousands of patients as a therapeutic treatment for diverse conditions. Given the profound inflammatory response observed in patients with COVID-19, and the successful completion of 10-patient pilot study of intravenous hAF, we present a trial design for a larger clinical trial of intravenous hAF for the treatment of COVID-19.

Precompetitive Consensus Building to Facilitate the Use of Digital Health Technologies to Support Parkinson Disease Drug Development through Regulatory Science.

Innovative tools are urgently needed to accelerate the evaluation and subsequent approval of novel treatments that may slow, halt, or reverse the relentless progression of Parkinson disease (PD). Therapies that intervene early in the disease continuum are a priority for the many candidates in the drug development pipeline. There is a paucity of sensitive and objective, yet clinically interpretable, measures that can capture meaningful aspects of the disease.

A Mixed Methods, Observational Investigation of Physical Activity, Exercise, and Diet Among Older Ugandans Living With and Without Chronic HIV Infection.

People living with HIV (PLWH) are at increased risk for cardiovascular disease. Physical activity, exercise, and controlled diet can mitigate this risk, yet these behaviors are understudied in sub-Saharan Africa. Our objective was to describe and compare the meaning, value, and patterns of physical activity, exercise, and diet among PLWH and older adults without HIV in Uganda.

Cats and Apples: Semantic Fluency Performance for Living Things Identifies Patients with Very Early Alzheimer's Disease.

Objective: Reduced semantic memory performance is a known neuropsychological marker of very early Alzheimer's disease (AD), but the task format that best predicts disease status is an open question. The present study aimed to identify the semantic fluency task and measure that best discriminates early-stage AD patients (PATs) from cognitively healthy controls.

Method: Semantic fluency performance for animals, fruits, tools, and vehicles was assessed in 70 early-stage AD PATs and 67 cognitively healthy participants.

Immunohistochemical Detection of Synuclein Pathology in Skin in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinsonism.

Background: Recent studies reported abnormal alpha-synuclein deposition in biopsy-accessible sites of the peripheral nervous system in Parkinson's disease (PD). This has considerable implications for clinical diagnosis. Moreover, if deposition occurs early, it may enable tissue diagnosis of prodromal PD.

Outcome measures based on digital health technology sensor data: data- and patient-centric approaches.

Digital health technology tools (DHTT) are technologies such as apps, smartphones, and wearables that remotely acquire health-related information from individuals. They have the potential advantages of objectivity and sensitivity of measurement, richness of high-frequency sensor data, and opportunity for passive collection of health-related data. Thus, DHTTs promise to provide patient phenotyping at an order of granularity several times greater than is possible with traditional clinical research tools.

Building a Machine-Learning Framework to Remotely Assess Parkinson's Disease Using Smartphones.

Objective: Parkinson's disease (PD) is a neurodegenerative disorder that affects multiple neurological systems. Traditional PD assessment is conducted by a physician during infrequent clinic visits. Using smartphones, remote patient monitoring has the potential to obtain objective behavioral data semi-continuously, track disease fluctuations, and avoid rater dependency.

Gallery Game: Smartphone-based assessment of long-term memory in adults at risk of Alzheimer's disease.

: Gallery Game, deployed within the Mezurio smartphone app, targets the processes of episodic memory hypothesized to be first vulnerable to neurofibrillary tau-related degeneration in Alzheimer's Disease, prioritizing both perirhinal and entorhinal cortex/hippocampal demands.: Thirty-five healthy adults (aged 40-59 years), biased toward those at elevated familial risk of dementia, completed daily Gallery Game tasks for a month. Assessments consisted of cross-modal paired-associate learning, with subsequent tests of recognition and free recall following delays ranging from one to 13 days.

The use of mobile computing devices in microsurgery.

Mobile computing devices (MCDs), such as smartphones and tablets, are revolutionizing medical practice. These devices are almost universally available and offer a multitude of capabilities, including online features, streaming capabilities, high-quality cameras, and numerous applications. Within the surgical field, MCDs are increasingly being used for simulations.

Progressive Decline in Gray and White Matter Integrity in Parkinson's Disease: An Analysis of Longitudinal Parkinson Progression Markers Initiative Diffusion Tensor Imaging Data.

Progressive neuronal loss in neurodegenerative diseases such as Parkinson's disease (PD) is associated with progressive degeneration of associated white matter tracts as measured by diffusion tensor imaging (DTI). These findings may have diagnostic and functional implications but their value in PD remains unknown. Here we analyzed longitudinal DTI data from Parkinson's Progression Markers Initiative PD patients for changes over time relative to healthy control (HC) participants.

Concussion Burden, Recovery, and Risk Factors in Elite Youth Ice Hockey Players.

Objective: To examine rates of concussion and more severe concussion (time loss of greater than 10 days) in elite 13- to 17-year-old ice hockey players.

Methods: This is a prospective cohort study (Alberta, Canada). Bantam (13-14 years) and Midget (15-17 years) male and female elite (top 20% by division of play) youth ice hockey players participated in this study.

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

Background: 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.

Objectives: The present study assessed the feasibility, reliability, and validity of smartphone-based digital biomarkers of PD in a clinical trial setting.

Methods: 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.

Parietal lobe critically supports successful paired immediate and single-item delayed memory for targets.

The parietal lobe is important for successful recognition memory, but its role is not yet fully understood. We investigated the parietal lobes' contribution to immediate paired-associate memory and delayed item-recognition memory separately for hits (targets) and correct rejections (distractors). We compared the behavioral performance of 56 patients with known parietal and medial temporal lobe dysfunction (i.

Neuropsychological Markers of Medial Perirhinal and Entorhinal Cortex Functioning are Impaired Twelve Years Preceding Diagnosis of Alzheimer's Dementia.

Neurofibrillary pathology in Alzheimer's dementia (AD) is associated with cognitive impairments and cortical thinning, and begins in medial perirhinal cortex (mPRC) before entering entorhinal cortex (ERC). Thus, mPRC dysfunction (e.g.

Cortical thinning of parahippocampal subregions in very early Alzheimer's disease.

The stereotypical pattern of neurofibrillary tangle spreading in the earliest stages of typical Alzheimer's dementia (AD) predicts that medial perirhinal cortex (mPRC) atrophy precedes entorhinal cortex (ERC) atrophy, whereas the status of the parahippocampal cortex (PHC) remains unclear. Atrophy studies have focused on more advanced rather than early AD patients, and usually segment the entire PRC as opposed to the mPRC versus lateral PRC (lPRC). The present study therefore determined the extent of ERC, mPRC, lPRC, and PHC atrophy in very early AD (mean Mini-Mental State Examination score = 26) patients and its presumed prodrome amnestic mild cognitive impairment (mean Mini-Mental State Examination score = 28) compared to demographically matched controls.

The 12 Years Preceding Mild Cognitive Impairment Due to Alzheimer's Disease: The Temporal Emergence of Cognitive Decline.

Background: The identification of the type and sequence of cognitive decline in preclinical mild cognitive impairment (MCI) prior to Alzheimer's disease (AD) is crucial for understanding AD pathogenesis and implementing therapeutic interventions.

Objective: To model the longitudinal courses of different neuropsychological functions in MCI due to AD.

Methods: We investigated the prodromal phase of MCI over a 12-year period in 27 initially healthy participants with subsequent MCI preceding AD (NC-MCI) and 60 demographically matched healthy individuals (NC-NC).