Mitapivat improves ineffective erythropoiesis and iron overload in adult patients with pyruvate kinase deficiency.

Pyruvate kinase (PK) deficiency is a rare, hereditary disease characterized by chronic hemolytic anemia. Iron overload is a common complication regardless of age, genotype, or transfusion history. Mitapivat, an oral, allosteric PK activator, improves anemia and hemolysis in adult patients with PK deficiency.

Mitapivat in adult patients with pyruvate kinase deficiency receiving regular transfusions (ACTIVATE-T): a multicentre, open-label, single-arm, phase 3 trial.

Background: Mitapivat, an oral activator of pyruvate kinase (PK) in red blood cells (RBCs), has shown significant improvements in haemoglobin and haemolysis among patients with pyruvate kinase deficiency who were not receiving regular transfusions. We aimed to evaluate the efficacy and safety of mitapivat in adults with pyruvate kinase deficiency receiving regular transfusions.

Methods: ACTIVATE-T was an open-label, single-arm, phase 3 trial conducted in 20 centres across Europe, North America, and Asia.

Vortioxetine 5, 10, and 20 mg significantly reduces the risk of relapse compared with placebo in patients with remitted major depressive disorder: The RESET study.

Background: Maintenance therapy for major depressive disorder (MDD) is typically recommended at the dose on which the patient was stabilized. However, for some patients, dose alteration may be required. We investigated multiple vortioxetine doses versus placebo for relapse prevention in patients achieving remission with vortioxetine 10 mg daily.

A phase 1b/2a study of soticlestat as adjunctive therapy in participants with developmental and/or epileptic encephalopathies.

Objective: To evaluate the safety, tolerability, and pharmacokinetics of soticlestat, a first-in-class cholesterol 24-hydroxylase inhibitor, in adults with developmental and/or epileptic encephalopathies (DEE).

Methods: The study comprised a 30-day, randomized, double-blind, placebo-controlled phase (Part A), followed by a 55-day open-label phase (Part B) (ClinicalTrials.gov ID: NCT03166215) .

A novel study design for investigating relapse prevention in major depressive disorder: Preliminary data from the open-label period of a phase 4 vortioxetine study.

Background: Traditional randomized withdrawal studies have assessed the efficacy of antidepressants for reducing relapse and recurrence of major depressive episodes (MDEs) but have not compared dose reduction, increase, or maintenance within the same study.

Methods: Here we present the development, implementation, and preliminary data from the open-label period of an ongoing phase 4, non-traditional, randomized withdrawal study. Designed to evaluate the efficacy of vortioxetine across its approved dose range for relapse prevention, the study enrolled adult patients with recurrent major depressive disorder (MDD), Montgomery-Åsberg Depression Rating Scale (MADRS) ≥ 26, and history of ≥2 MDEs.

Using self-reported vocational functioning measures to identify employed patients with impaired functional capacity in major depressive disorder.

Background: Patients with major depressive disorder (MDD) show impairments in cognitive functioning, including deficits on performance-based measures of functional capacity. A proportion of patients with MDD may achieve higher scores at baseline, and may not show a detectable response to treatment. How to identify these cases is the goal of this investigation.

Hazard ratio inference in stratified clinical trials with time-to-event endpoints and limited sample size.

The stratified Cox model is commonly used for stratified clinical trials with time-to-event endpoints. The estimated log hazard ratio is approximately a weighted average of corresponding stratum-specific Cox model estimates using inverse-variance weights; the latter are optimal only under the (often implausible) assumption of a constant hazard ratio across strata. Focusing on trials with limited sample sizes (50-200 subjects per treatment), we propose an alternative approach in which stratum-specific estimates are obtained using a refined generalized logrank (RGLR) approach and then combined using either sample size or minimum risk weights for overall inference.

Association between mesothelioma and non-occupational asbestos exposure: systematic review and meta-analysis.

Background: The risk of mesothelioma has been shown to be associated with exposure to asbestos fibers. Most of the existing literature focuses on occupational exposure; however, non-occupational asbestos exposure has also been identified as an important risk factor.

Objective: To estimate the association between mesothelioma and non-occupational asbestos exposure, and evaluate control recruitment and exposure measurement methods.

Incorporating baseline measurements into the analysis of crossover trials with time-to-event endpoints.

Two-period two-treatment (2×2) crossover designs are commonly used in clinical trials. For continuous endpoints, it has been shown that baseline (pretreatment) measurements collected before the start of each treatment period can be useful in improving the power of the analysis. Methods to achieve a corresponding gain for censored time-to-event endpoints have not been adequately studied.

Framework for assessment and phytoremediation of asbestos-contaminated sites.

We examine the feasibility of phytoremediation as an alternative strategy to limit the exposure of asbestos in site with asbestos-containing materials. We collected soils from four locations from two sites-one with naturally occurring asbestos, and another, a superfund site, where asbestos-containing materials were disposed over decades-and performed ecotoxicology tests. We also performed two experiments with crop cultivar and two grasses from serpentine ecotype and cultivar to determined best choice for phytoremediation.

Comparison of statistical methods for detection of serum lipid biomarkers for mesothelioma and asbestos exposure.

Aim: We compared three statistical methods in selecting a panel of serum lipid biomarkers for mesothelioma and asbestos exposure.

Materials & Methods: Serum samples from mesothelioma, asbestos-exposed subjects and controls (40 per group) were analyzed. Three variable selection methods were considered: top-ranked predictors from univariate model, stepwise and least absolute shrinkage and selection operator.

The impact of parental history on children's risk of asthma: a study based on the National Health and Nutrition Examination Survey-III.

Purpose: This study aimed to examine the separate effects of maternal and paternal history on the onset of asthma in children and evaluate the relationship between age of asthma onset in parents and risk of asthma in their children.

Methods: We used data from the third National Health and Nutrition Examination Survey. We developed new continuous standardized scores for survey data to quantify parental history that incorporated both the occurrence of asthma and the age at onset, and associated these scores with asthma risk in the children.

Urinary incontinence and disability in community-dwelling women: a cross-sectional study.

Aims: Disability, an individual's reduced capacity to perform physical tasks encountered in daily routine, is associated with urinary incontinence in the elderly. Our objective was to determine if urinary incontinence is associated with disability in community-dwelling women 40 years and older.

Methods: Cross-sectional study among US women ≥40 years (n = 4,458) from National Health and Nutrition Examination Surveys 2005-2010.