ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma.

Purpose: Pharmacologic therapies for neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PNs) are limited; currently, none are US Food and Drug Administration-approved for adults.

Methods: ReNeu is an open-label, multicenter, pivotal, phase IIb trial of mirdametinib in 58 adults (≥18 years of age) and 56 children (2 to 17 years of age) with NF1-PN causing significant morbidities. Patients received mirdametinib capsules or tablets for oral suspension (2 mg/m twice daily, maximum 4 mg twice daily), regardless of food intake, in 3 weeks on/1 week off 28-day cycles.

Probability of Response in the First Sixteen Weeks After Starting Biologics: An Analysis of Juvenile Idiopathic Arthritis Biologics Trials.

Objectives: Most juvenile idiopathic arthritis (JIA) biologic disease-modifying antirheumatic drugs (bDMARDs) trials used an open-label run-in period followed by randomized medication withdrawal. We used data from the run-in period of 4 bDMARD trials to 1) delineate early response trajectory to bDMARDs and 2) identify predictors of early response.

Methods: Data from the first 16 weeks of 4 bDMARD trials were used.

Latent classes of early response trajectories to biologics initiation in juvenile idiopathic arthritis: an analysis of four trials.

Aims: 1) To delineate latent classes of treatment response to biologics in juvenile idiopathic arthritis (JIA) patients in the first 16 weeks after initiation. 2) To identify predictors of early disease response.

Methods: The study population was drawn from four biologics trials in polyarticular course JIA: Etanercept 2000, Abatacept 2008, TRial of Early Aggressive Therapy (TREAT) 2012 and Tocilizumab 2014.

Quantifying the extent of visit irregularity in longitudinal data.

The timings of visits in observational longitudinal data may depend on the study outcome, and this can result in bias if ignored. Assessing the extent of visit irregularity is important because it can help determine whether visits can be treated as repeated measures or as irregular data. We propose plotting the mean proportions of individuals with 0 visits per bin against the mean proportions of individuals with >1 visit per bin as bin width is varied and using the area under the curve (AUC) to assess the extent of irregularity.

Efficacy, Safety, and Pharmacodynamic Effects of the Bruton's Tyrosine Kinase Inhibitor Fenebrutinib (GDC-0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: Fenebrutinib (GDC-0853) is a noncovalent, oral, and highly selective inhibitor of Bruton's tyrosine kinase (BTK). The efficacy, safety, and pharmacodynamics of fenebrutinib in systemic lupus erythematosus (SLE) were assessed in this phase II, multicenter, randomized, placebo-controlled study.

Methods: Patients who had moderately to severely active SLE while receiving background standard therapy were randomized to receive placebo, fenebrutinib 150 mg once daily, or fenebrutinib 200 mg twice daily.

Summarizing the extent of visit irregularity in longitudinal data.

Background: Observational longitudinal data often feature irregular, informative visit times. We propose descriptive measures to quantify the extent of irregularity to select an appropriate analytic outcome approach.

Methods: We divided the study period into bins and calculated the mean proportions of individuals with 0, 1, and > 1 visits per bin.

Cancer survivorship and opioid prescribing rates: A population-based matched cohort study among individuals with and without a history of cancer.

Background: Little is known about opioid prescribing among individuals who have survived cancer. Our aim is to examine a predominantly socio-economically disadvantaged population for differences in opioid prescribing rates among cancer survivors compared with matched controls without a prior diagnosis of cancer.

Methods: This was a retrospective population-wide matched cohort study.

Trends in unintentional injury mortality in Canadian children 1950-2009 and association with selected population-level interventions.

Objectives: To examine unintentional injury mortality rates in children (0-19 years) in Canada from 1950 to 2009 against national population-level injury prevention interventions.

Methods: Injury mortality rates were age and sex adjusted. Changes in trend and level of mortality rates were assessed at pre-specified intervention periods using segmented linear regression analyses for interrupted time series.

Trends and Outcomes of Patent Ductus Arteriosus Treatment in Very Preterm Infants in Canada.

 To assess trends in patent ductus arteriosus (PDA) management and examine concurrent changes in neonatal mortality and morbidities.  This retrospective observational study examined infants born at 23 to 32 weeks' gestational age with PDA and admitted to a neonatal unit during 2006 to 2012. Multivariable logistic regression assessed trends in yearly PDA treatment rates and compared a composite outcome of mortality or any severe morbidity (bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, or necrotizing enterocolitis) between and within time periods and PDA treatments.