Real-world experience with long-term albumin in patients with cirrhosis and ascites.

Background & Aims: Long-term albumin (LTA) is currently standard of care for patients with decompensated cirrhosis in many Italian hepatology centres. In this real-life study, we aimed to describe patient, logistical and treatment-related characteristics in daily clinical practice and to identify predictors of response.

Methods: We performed a multicentre, retrospective, observational study in patients with cirrhosis and ascites receiving LTA between 01/2016 and 02/2022 and followed until death, TIPS (transjugular intrahepatic portosystemic shunt) placement, transplantation or 02/2023.

Comparing machine learning and deep learning models to predict cognition progression in Parkinson's disease.

Cognitive decline in Parkinson's disease (PD) varies widely. While models to predict cognitive progression exist, comparing traditional probabilistic models to deep learning methods remains understudied. This study compares sequential modeling techniques to identify cognitive progression in individuals with and without PD.

Eleven Years of Change: Disease Progression in Biomarker-Defined Sporadic Parkinson's Disease.

Long-term longitudinal data on outcomes in sporadic Parkinson's Disease are limited, especially from cohorts with extensive biological characterization. Recent advances in biomarkers characterization of Parkinson's Disease necessitate an updated examination of long-term progression within contemporary cohorts like the Parkinson's Progression Markers Initiative, which enrolled individuals within 2 years of clinical diagnosis of Parkinson's Disease. Our study leverages the Neuronal Synuclein Disease framework, which defines the disease based on biomarker assessed presence of neuronal alpha-synuclein and dopamine deficit, rather than based on conventional clinical diagnostic criteria.

Predicting Cerebrospinal Fluid Alpha-Synuclein Seed Amplification Assay Status from Demographics and Clinical Data.

Objective: To develop and externally validate models to predict probabilities of alpha-synuclein (a-syn) positive or negative status in vivo in a mixture of people with and without Parkinson's disease (PD) using easily accessible clinical predictors.

Methods: Uni- and multi-variable logistic regression models were developed in a cohort of participants from the Parkinson Progression Marker Initiative (PPMI) study to predict cerebrospinal fluid (CSF) a-syn status as measured by seeding amplification assay (SAA). Models were externally validated in a cohort of participants from the Systemic Synuclein Sampling Study (S4) that had also measured CSF a-syn status using SAA.

The Role of Transjugular Intrahepatic Portosystemic Shunt for the Management of Ascites in Patients with Decompensated Cirrhosis.

The development and progression of ascites represent a crucial event in the natural history of patients with cirrhosis, predisposing them to other complications and carrying a heavy impact on prognosis. The current standard of care for the management of ascites relies on various combinations of diuretics and large-volume paracenteses. Periodic long-term albumin infusions on top of diuretics have been recently shown to greatly facilitate the management of ascites.

Transdermal Nicotine Treatment and Progression of Early Parkinson's Disease.

BACKGROUND: Epidemiologic studies show that smokers have a lower incidence of Parkinson’s disease. Nicotine has been hypothesized to slow progression in early Parkinson’s disease. METHODS: In a double-blind, placebo-controlled multicenter trial, we randomly assigned patients with Parkinson’s disease, diagnosed within 18 months, who were in Hoehn and Yahr disease stage less than or equal to 2 (range from 0 to 5; higher scores indicate greater impairment), who were therapy naïve (except for stable monoamine-oxidase-B inhibition), and not requiring dopaminergic therapy, to transdermal nicotine or placebo.

Predictors of clinical trajectories of patients with acutely decompensated cirrhosis. An external validation of the PREDICT study.

Background And Aims: The PREDICT study recently showed that acutely decompensated (AD) patients with cirrhosis can present three different clinical phenotypes in the 90 days after admission: (1) pre-ACLF, developing acute-on-chronic liver failure (ACLF); (2) unstable decompensated cirrhosis (UDC), being re-admitted for AD without ACLF and (3) stable decompensated cirrhosis (SDC), not presenting readmission or ACLF. This study aimed to externally validate the existence of these three distinct trajectories and to identify predictors for the occurrence of each trajectory.

Methods: Baseline data, 3-month ACLF and readmission incidence and 1-year survival were analysed in a prospective cohort of patients admitted for AD.

Diagnostic value of anti-integrin αvβ6 antibodies in ulcerative colitis.

Ulcerative colitis (UC)-related mucosal inflammation is characterized by the production of various autoantibodies with limited clinical relevance. Recent studies have shown that circulating levels of IgG against integrin αvβ6 are increased in UC patients as compared to Crohn's disease (CD) patients and healthy controls (HC). The present study assessed the diagnostic value of circulating IgG anti-αvβ6 in UC.

Predicting Ambulatory Capacity in Parkinson's Disease to Analyze Progression, Biomarkers, and Trial Design.

Background: In Parkinson's disease (PD), gait and balance is impaired, relatively resistant to available treatment and associated with falls and disability. Predictive models of ambulatory progression could enhance understanding of gait/balance disturbances and aid in trial design.

Objectives: To predict trajectories of ambulatory abilities from baseline clinical data in early PD, relate trajectories to clinical milestones, compare biomarkers, and evaluate trajectories for enrichment of clinical trials.

Reversibility of Frail Phenotype in Patients with Inflammatory Bowel Diseases.

It was recently reported that frailty status can negatively influence the clinical course of patients with inflammatory bowel diseases (IBDs). Our recent study demonstrated that 20% of patients with an IBD are frail, and disease activity increases the risk of frailty. In the present study, we prospectively monitored this subgroup of frail patients, assessed whether the frailty status was reversible, and analyzed factors associated with frailty reversibility.

Developing better digital health measures of Parkinson's disease using free living data and a crowdsourced data analysis challenge.

One of the promising opportunities of digital health is its potential to lead to more holistic understandings of diseases by interacting with the daily life of patients and through the collection of large amounts of real-world data. Validating and benchmarking indicators of disease severity in the home setting is difficult, however, given the large number of confounders present in the real world and the challenges in collecting ground truth data in the home. Here we leverage two datasets collected from patients with Parkinson's disease, which couples continuous wrist-worn accelerometer data with frequent symptom reports in the home setting, to develop digital biomarkers of symptom severity.

Frail Phenotype in Patients With Inflammatory Bowel Disease.

Background: Recent retrospective studies have shown that frailty is common in hospitalized patients with inflammatory bowel disease (IBD) and enhances the risk of drug-related infections, postsurgery complications, hospital readmissions, and mortality, independently of age and comorbidities. We carried out a descriptive cohort study to evaluate the frequency of frail phenotype in IBD and analyzed the risk factors associated with this condition.

Methods: Frail phenotype was assessed in IBD patients by using the Fried frailty phenotype.

A Smartphone Application as an Exploratory Endpoint in a Phase 3 Parkinson's Disease Clinical Trial: A Pilot Study.

Background: Smartphones can generate objective measures of Parkinson's disease (PD) and supplement traditional in-person rating scales. However, smartphone use in clinical trials has been limited.

Objective: This study aimed to determine the feasibility of introducing a smartphone research application into a PD clinical trial and to evaluate the resulting measures.

Re-Analysis of the STEADY-PD II Trial-Evidence for Slowing the Progression of Parkinson's Disease.

Background: Recent examination of the STEADY-PD III isradipine clinical trial data concluded that early-stage Parkinson's disease (PD) participants who had longer exposure to isradipine had a significant delay in their need for symptomatic medication, as well as a lower medication burden at the end of the trial. These findings suggest that greater exposure to isradipine might slow disease progression.

Objectives: To test this hypothesis, the data from the STEADY-PD II isradipine clinical trial, in which an extended-release (ER) formulation of the drug was used, was re-examined.

A Disease Progression Model to Quantify the Nonmotor Symptoms of Parkinson's Disease in Participants With Leucine-Rich Repeat Kinase 2 Mutation.

Leucine-rich repeat kinase 2 (LRRK2) inhibitors are currently in clinical development as interventions to slow progression of Parkinson's disease (PD). Understanding the rate of progression in PD as measured by both motor and nonmotor features is particularly important in assessing the potential therapeutic effect of LRRK2 inhibitors in clinical development. Using standardized data from the Critical Path for Parkinson's Unified Clinical Database, we quantified the rate of progression of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I (nonmotor aspects of experiences of daily living) in 158 participants with PD who were carriers and 598 participants with PD who were noncarriers of at least one of three different LRRK2 gene mutations (G2019S, R1441C/G, or R1628P).

Isradipine plasma pharmacokinetics and exposure-response in early Parkinson's disease.

Objectives: Isradipine is a dihydropyridine calcium channel inhibitor that has demonstrated concentration-dependent neuroprotective effects in animal models of Parkinson's disease (PD) but failed to show efficacy in a phase 3 clinical trial. The objectives of this study were to model the plasma pharmacokinetics of isradipine in study participants from the phase 3 trial; and, to investigate associations between drug exposure and longitudinal clinical outcome measures of PD progression.

Methods: Plasma samples from nearly all study participants randomized to immediate-release isradipine 5-mg twice daily (166 of 170) were collected for population pharmacokinetic modeling.

Efficacy of Nilotinib in Patients With Moderately Advanced Parkinson Disease: A Randomized Clinical Trial.

Importance: There is a critical need for careful and independent validation of reported symptomatic efficacy and dopaminergic biomarker changes induced by nilotinib in Parkinson disease (PD).

Objectives: To assess safety and tolerability of nilotinib in participants with moderately advanced PD. Secondary and exploratory objectives were to assess its affect on PD disability, pharmacokinetics, cerebrospinal fluid (CSF) penetration, and biomarkers.

Pharmacotherapy Use for Non-Motor Symptoms Among de novo Parkinson's Disease Parkinson's Progression Markers Initiative Participants.

Parkinson's disease (PD) patients experience a range of non-motor symptoms that are believed to be related to disease pathophysiology, many of which are treatable by medications. Among newly-diagnosed PD participants in the Parkinson's Progression Markers Initiative study, we describe (1) the frequency of medication use for common non-motor symptoms, and (2) when non-motor symptomatic treatment was initiated relative to PD diagnosis. Non-motor medication use was reported by 73% of participants, most commonly for depression, constipation, and anxiety.

Toward precision prescribing for methadone: Determinants of methadone deposition.

Background: Despite the World Health Organization listing methadone as an essential medication, effective dose selection is challenging, especially in racial and ethnic minority populations. Subtherapeutic doses can result in withdrawal symptoms while supratherapeutic doses can result in overdose and death. Although CYP3A4 was conventionally considered the principal methadone metabolizing enzyme, more recent data have identified CYP2B6 as the principal enzyme.

Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection: The AIDS Clinical Trials Group A5335S Substudy.

Background: Direct-acting antivirals (DAAs) targeting hepatitis C virus (HCV) have revolutionized outcomes in human immunodeficiency virus (HIV) coinfection.

Methods: We examined early events in liver and plasma through A5335S, a substudy of trial A5329 (paritaprevir/ritonavir, ombitasvir, dasabuvir, with ribavirin) that enrolled chronic genotype 1a HCV-infected persons coinfected with suppressed HIV: 5 of 6 treatment-naive enrollees completed A5335S.

Results: Mean baseline plasma HCV ribonucleic acid (RNA) = 6.

Understanding the role of threading dislocations on 4H-SiC MOSFET breakdown under high temperature reverse bias stress.

The origin of dielectric breakdown was studied on 4H-SiC MOSFETs that failed after three months of high temperature reverse bias stress. A local inspection of the failed devices demonstrated the presence of a threading dislocation (TD) at the breakdown location. The nanoscale origin of the dielectric breakdown was highlighted with advanced high-spatial-resolution scanning probe microscopy (SPM) techniques.

Raltegravir pharmacokinetics before and during treatment with ombitasvir, paritaprevir/ritonavir plus dasabuvir in adults with human immunodeficiency virus-1 and hepatitis C virus coinfection: AIDS Clinical Trials Group sub-study A5334s.

Aims: AIDS Clinical Trials Group study A5334s evaluated the pharmacokinetics of raltegravir before and during combined administration of ombitasvir, paritaprevir/ritonavir, plus dasabuvir (OBV/PTV/r + DSV) and weight-based ribavirin in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfected adults. The pharmacokinetics of OBV/PTV/r + DSV during raltegravir coadministration were also characterized.

Methods: Adults living with HIV/HCV coinfection receiving steady-state raltegravir (400 mg twice daily) with 2 nucleos(t)ide analogues were enrolled.