Study on different fractional CO laser parameters combined with halometasone in treatment of chronic eczema.

This prospective study aimed to investigate the efficacy and safety of fractional CO laser with different parameters, in combination with topical halometason, for the management of chronic eczema. Each lesion of the patients were divided into four groups and given fractional CO laser treatment with different parameter and a negative control. After treatment, all four groups were treated with topical halometasone cream once daily for a week.

A randomized, double-blind, placebo-controlled, phase 2b study of the efficacy and safety of velusetrag in subjects with diabetic or idiopathic gastroparesis.

Background: This study assessed the efficacy and safety of velusetrag-a 5-HT agonist with pan-gastrointestinal prokinetic activity-for gastroparesis symptom management and gastric emptying (GE).

Methods: In this multicenter, double-blind, randomized, placebo-controlled study, subjects with diabetic or idiopathic gastroparesis received velusetrag 5, 15, or 30 mg or placebo for 12 weeks. The primary efficacy outcome was a 7-day mean Gastroparesis Cardinal Symptom Index 24-h composite score (GCSI-24H) change from baseline at week 4; GE was evaluated using scintigraphy (GES) and breath tests, and safety from adverse events (AEs).

Effects of solriamfetol on on-the-road driving in participants with narcolepsy: A randomised crossover trial.

Objective: To evaluate the impact of solriamfetol, a dopamine and norepinephrine reuptake inhibitor, on on-the-road driving performance in participants with narcolepsy.

Methods: In this randomised, double-blind, placebo-controlled, crossover study, driving performance during a 1 h on-road driving test was assessed at 2 and 6 h post-dose following 7 days of treatment with solriamfetol (150 mg/day for 3 days, followed by 300 mg/day for 4 days) or placebo. The primary endpoint was standard deviation of lateral position (SDLP) at 2 h post-dose.

Effects of solriamfetol on on-the-road driving performance in participants with excessive daytime sleepiness associated with obstructive sleep apnoea.

Objective: To evaluate the impact of solriamfetol, a dopamine and norepinephrine reuptake inhibitor, on on-the-road driving in participants with excessive daytime sleepiness (EDS) associated with obstructive sleep apnoea (OSA).

Methods: Eligible participants were aged 21-75 years with OSA and EDS (Maintenance of Wakefulness Test mean sleep latency <30 minutes and Epworth Sleepiness Scale score ≥10). Participants were randomised 1:1 to solriamfetol (150 mg/day [3 days], then 300 mg/day [4 days]) or placebo for 7 days, before crossover to the other treatment paradigm.

Safety, Pharmacokinetics, and Pharmacodynamics of TD-0714, a Novel Potent Neprilysin Inhibitor in Healthy Adult and Elderly Subjects.

TD-0714 is an orally active, potent, and selective inhibitor of human neprilysin (NEP) in development for the treatment of chronic heart failure. Oral administration of TD-0714 in rats resulted in dose-dependent and sustained increases in plasma cyclic guanosine monophosphate (cGMP) over 24 hours consistent with NEP target engagement. Randomized, double-blind, placebo controlled, single ascending dose (50-600 mg TD-0714) and multiple ascending dose (10-200 mg TD-0714 q.

Minimal Residual Disease Status as a Surrogate Endpoint for Progression-free Survival in Newly Diagnosed Multiple Myeloma Studies: A Meta-analysis.

Background: Therapeutic advances have greatly extended survival times in patients with multiple myeloma, necessitating increasingly lengthy trials when using survival outcomes as primary endpoints. A surrogate endpoint that can more rapidly predict survival could accelerate drug development. We conducted a meta-analysis to evaluate minimal residual disease (MRD) status as a valid progression-free survival (PFS) surrogate in patients with newly diagnosed multiple myeloma (NDMM).

A Network Reduction-Based Multiobjective Evolutionary Algorithm for Community Detection in Large-Scale Complex Networks.

Evolutionary algorithms have been demonstrated to be very competitive in the community detection for complex networks. They, however, show poor scalability to large-scale networks due to the exponential increase of search space. In this paper, we suggest a network reduction-based multiobjective evolutionary algorithm for community detection in large-scale networks, where the size of the networks is recursively reduced as the evolution proceeds.

Robust inference for group sequential trials.

For ethical reasons, group sequential trials were introduced to allow trials to stop early in the event of extreme results. Endpoints in such trials are usually mortality or irreversible morbidity. For a given endpoint, the norm is to use a single test statistic and to use that same statistic for each analysis.

A single test for rejecting the null hypothesis in subgroups and in the overall sample.

In clinical trials, some patient subgroups are likely to demonstrate larger effect sizes than other subgroups. For example, the effect size, or informally the benefit with treatment, is often greater in patients with a moderate condition of a disease than in those with a mild condition. A limitation of the usual method of analysis is that it does not incorporate this ordering of effect size by patient subgroup.

Inference from blinded data in randomized clinical trials.

Background: With blinded data, several authors have concluded that there is a negligible chance of inferring a non-null treatment effect. The recent Food and Drug Administration (FDA) draft guidance document on adaptive trials, by encouraging blinded sample size reestimation, implies the same.

Purpose: We derive methods to investigate whether the probability of inferring a treatment effect is much larger than previously thought, and whether that is of concern.

The benefit of stratification in clinical trials revisited.

Stratification is common in clinical trials because it can reduce the variance of the estimated treatment effect. The traditional demonstration of variance reduction relies on the assumption of stratum sizes being fixed quantities. However, in practice, to speed up enrollment, and to obtain a study population with a similar distribution as the overall population, the stratum sizes are allowed to vary.

A Unified Approach to Nonparametric Comparison of Receiver Operating Characteristic Curves for Longitudinal and Clustered Data.

We present a unified approach to nonparametric comparisons of receiver operating characteristic (ROC) curves for a paired design with clustered data. Treating empirical ROC curves as stochastic processes, their asymptotic joint distribution is derived in the presence of both between-marker and within-subject correlations. A Monte Carlo method is developed to approximate their joint distribution without involving nonparametric density estimation.

Alcohol use, comorbidity, and mortality.

Objectives: To examine the combined influence of alcohol use and comorbidity on 20-year mortality in older adults (average age 66 at the time of the baseline survey).

Design: Longitudinal analysis of a national probability sample-based cohort study.

Setting: Data sources were the National Health and Nutrition Examination Survey I (NHANES I), 1971-1974, and the NHANES Epidemiologic Followup Survey, 1992.

Longitudinal trajectories of heavy drinking in adults in the United States of America.

Aims: To estimate age, period, cohort and other demographic influences on heavy alcohol consumption and trajectories of heavy drinking in American adults.

Design: Prospective cohort of 14 127 participants, aged 25-74 years at baseline. Generalized estimating equations to model longitudinal change in the probability of heavy drinking and its association with demographic factors.

The effects of megestrol acetate suspension for elderly patients with reduced appetite after hospitalization: a phase II randomized clinical trial.

Objectives: To provide preliminary evidence on the effectiveness and optimal dosage of megestrol acetate for older persons with impaired appetite after hospitalization.

Design: Randomized clinical trial.

Setting: Acute care hospital.

Longitudinal patterns and predictors of alcohol consumption in the United States.

Objectives: We examined demographic predictors of longitudinal patterns in alcohol consumption.

Methods: We used mixed-effects models to describe individual alcohol consumption and change in consumption with age, as well as the associations between consumption and birth year, national alcohol consumption, and demographic factors, among 14 105 adults from the National Health and Nutrition Examination Survey I Epidemiologic Follow-Up Study.

Results: Alcohol consumption declined with increasing age, and individual consumption mirrored national consumption.