Comparative Safety of Ultrasound Enhancing Agents: A Systematic Review and Bayesian Network Meta-Analysis.

Ultrasound enhancing agents (UEAs), including Optison, DEFINITY, and LUMASON, enhance the diagnostic performance of echocardiography, particularly, in patients with suboptimal acoustic windows. However, there remains a paucity of comparative safety assessments among the Food and Drug Administration-approved UEAs. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic literature review performed in August 2023 searched Medline, Embase, Cochrane Library, and gray literature.

Assessing Quality of Life, Economic Burden, and Independence Across the Alzheimer's Disease Continuum Using Patient-Caregiver Dyad Surveys.

Background: Alzheimer's disease (AD) and mild cognitive impairment (MCI) have negative quality of life (QoL) and economic impacts on patients and their caregivers and may increase along the disease continuum from MCI to mild, moderate, and severe AD.

Objective: To assess how patient and caregiver QoL, indirect and intangible costs are associated with MCI and AD severity.

Methods: An on-line survey of physician-identified patient-caregiver dyads living in the United States was conducted from June-October 2022 and included questions to both patients and their caregivers.

Minimal clinically important differences in six-minute walking distance in late-onset Pompe disease.

Background: The minimal clinically important difference (MCID) is the smallest change in outcome that physicians or patients would consider meaningful and is relevant when evaluating disease progression or the efficacy of interventions. Studies of patients with late-onset Pompe disease (LOPD) have used the 6-min walk distance (6MWD) as an endpoint to assess motor function. However, an MCID for 6MWD (% predicted and meters) has yet to be established in LOPD.

Validation of the Patient-Reported Outcomes Measurement Information System (PROMIS) physical function questionnaire in late-onset Pompe disease using PROPEL phase 3 data.

Background: The construct validity and interpretation of the Patient-Reported Outcome Measurement Information System (PROMIS) Physical Function short form 20a (PF20a) questionnaire were evaluated for patients with late-onset Pompe disease (LOPD), a rare, autosomal recessive, progressive neuromuscular disorder treatable by enzyme replacement therapy (ERT).

Methods: In the phase 3 PROPEL study, adults with LOPD underwent testing of physical functioning and had PRO measurements at baseline and at weeks 12, 26, 38, and 52 while receiving experimental or standard-of-care ERT. All patients were pooled for analyses, without comparisons between treatment groups.

Estimating Transition Probabilities Across the Alzheimer's Disease Continuum Using a Nationally Representative Real-World Database in the United States.

Introduction: Clinical Alzheimer's disease (AD) begins with mild cognitive impairment (MCI) and progresses to mild, moderate, or severe dementia, constituting a disease continuum that eventually leads to death. This study aimed to estimate the probabilities of transitions across those disease states.

Methods: We developed a mixed-effects multi-state Markov model to estimate the transition probabilities, adjusted for 5 baseline covariates, using the Health and Retirement Study (HRS) database.

Long-Term Climate Treaties with a Refunding Club.

We show that an appropriately-designed "Refunding Club" can simultaneously solve both free-riding problems in mitigating climate change-participating in a coalition with an emission reduction target and enduring voluntary compliance with the target once the coalition has been formed. Countries in the Club pay an initial fee into a fund that is invested in assets. In each period, part of the fund is distributed among the Club members in relation to the emission reductions they have achieved, suitably rescaled by a weighting factor.

Modelling Decline in Cognition to Decline in Function in Alzheimer's Disease.

Objectives: The study aimed to evaluate and quantify the temporal link between cognitive and functional decline, and assess the impact of the apolipoprotein E4 (APOE-e4) genotype on Alzheimer's disease (AD) progression.

Methods: A nonlinear mixed-effects Emax model was developed using longitudinal data from 659 patients with dementia due to AD sourced from the Alzheimer's disease neuroimaging initiative (ADNI) database. A cognitive decline model was first built using a cognitive subscale of the AD assessment scale (delayed word recall) as the endpoint, followed by a functional decline model, using the functional assessment questionnaire (FAQ) as the endpoint.

Prediction of Real-World Drug Effectiveness Prelaunch: Case Study in Rheumatoid Arthritis.

Background: Decision makers often need to assess the real-world effectiveness of new drugs prelaunch, when phase II/III randomized controlled trials (RCTs) but no other data are available.

Objective: To develop a method to predict drug effectiveness prelaunch and to apply it in a case study in rheumatoid arthritis (RA).

Methods: The approach 1) identifies a market-approved treatment ( S) currently used in a target population similar to that of the new drug ( N); 2) quantifies the impact of treatment, prognostic factors, and effect modifiers on clinical outcome; 3) determines the characteristics of patients likely to receive N in routine care; and 4) predicts treatment outcome in simulated patients with these characteristics.

Rheumatoid arthritis patients treated in trial and real world settings: comparison of randomized trials with registries.

Objective: To investigate whether patients with RA enrolled in randomized controlled trials (RCTs) and observational studies may differ in terms of characteristics that could modify treatment effects, leading to an efficacy-effectiveness gap.

Methods: We conducted systematic literature reviews to identify RCTs and observational studies with RA, treated with rituximab, tocilizumab or etanercept. We extracted baseline characteristics and compared the data of RCTs and observational studies using fixed-effects meta-analyses for the RCTs and random-effects meta-analyses for the observational studies.

GetReal in mathematical modelling: a review of studies predicting drug effectiveness in the real world.

The performance of a drug in a clinical trial setting often does not reflect its effect in daily clinical practice. In this third of three reviews, we examine the applications that have been used in the literature to predict real-world effectiveness from randomized controlled trial efficacy data. We searched MEDLINE, EMBASE from inception to March 2014, the Cochrane Methodology Register, and websites of key journals and organisations and reference lists.

Get real in individual participant data (IPD) meta-analysis: a review of the methodology.

Individual participant data (IPD) meta-analysis is an increasingly used approach for synthesizing and investigating treatment effect estimates. Over the past few years, numerous methods for conducting an IPD meta-analysis (IPD-MA) have been proposed, often making different assumptions and modeling choices while addressing a similar research question. We conducted a literature review to provide an overview of methods for performing an IPD-MA using evidence from clinical trials or non-randomized studies when investigating treatment efficacy.

Effect of gemfibrozil, rifampicin, or probenecid on the pharmacokinetics of the SGLT2 inhibitor empagliflozin in healthy volunteers.

Background: Empagliflozin is a potent, oral, selective inhibitor of sodium glucose cotransporter 2 in development for the treatment of type 2 diabetes mellitus.

Objective: The goal of these studies was to investigate potential drug-drug interactions between empagliflozin and gemfibrozil (an organic anion-transporting polypeptide 1B1 [OATP1B1]/1B3 and organic anion transporter 3 [OAT3] inhibitor), rifampicin (an OATP1B1/1B3 inhibitor), or probenecid (an OAT3 and uridine diphosphate glucuronosyltransferase inhibitor).

Methods: Two open-label, randomized, crossover studies were undertaken in healthy subjects.