Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial.

Background: Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38β MAPK) for the treatment of facioscapulohumeral muscular dystrophy.

Quantitative Muscle Analysis in FSHD Using Whole-Body Fat-Referenced MRI: Composite Scores for Longitudinal and Cross-sectional Analysis.

Background And Objectives: Facioscapulohumeral muscular dystrophy (FSHD) is a rare, debilitating disease characterized by progressive muscle weakness. MRI is a sensitive assessment of disease severity and progression. We developed a quantitative whole-body (WB) musculoskeletal MRI (WB-MSK-MRI) protocol analyzing muscles in their entirety.

Quantitative muscle analysis in facioscapulohumeral muscular dystrophy using whole-body fat-referenced MRI: Protocol development, multicenter feasibility, and repeatability.

Introduction/aims: Functional performance tests are the gold standard to assess disease progression and treatment effects in neuromuscular disorders. These tests can be confounded by motivation, pain, fatigue, and learning effects, increasing variability and decreasing sensitivity to disease progression, limiting efficacy assessment in clinical trials with small sample sizes. We aimed to develop and validate a quantitative and objective method to measure skeletal muscle volume and fat content based on whole-body fat-referenced magnetic resonance imaging (MRI) for use in multisite clinical trials.

Phase 1 clinical trial of losmapimod in facioscapulohumeral dystrophy: Safety, tolerability, pharmacokinetics, and target engagement.

Aims: Evaluate safety, tolerability, pharmacokinetics (PK) and target engagement (TE) of losmapimod in blood and muscle in facioscapulohumeral dystrophy (FSHD).

Methods: This study included Part A: 10 healthy volunteers randomized to single oral doses of losmapimod (7.5 mg then 15 mg; n = 8) or placebo (both periods; n = 2); Part B: 15 FSHD subjects randomized to placebo (n = 3), or losmapimod 7.

Rituximab utilization for approved and off-label nononcology indications and patients' experiences with the Patient Alert Card.

This study used retrospective chart review and survey data to evaluate: (1) off-label use of rituximab (MabThera/Rituxan) in autoimmune conditions and (2) patients' receipt and knowledge of the Patient Alert Card (PAC), a risk minimization measure for progressive multifocal leukoencephalopathy (PML) and serious infections. Anonymized patient data were collected from infusion centers in Europe from December 2015 to July 2017. Adults receiving rituximab in the same centers were provided a self-administered survey.

Persistence of immunity after vaccination with a capsular group B meningococcal vaccine in 3 different toddler schedules.

Background: One schedule for the capsular group B meningococcal vaccine 4CMenB is 2 doses that are administered 2 months apart for children aged 12-23 months, with a booster dose 12-24 months later. Our objective was to provide data on persistence of human serum bactericidal antibody (hSBA) titres in children up to 4 years of age after initial doses at 12-24 months, and immunogenicity of a booster dose at 48 months of age compared with vaccine-naive children.

Methods: Children previously immunized, as part of a randomized controlled trial, with 2 doses of 4CMenB vaccine at 12-24 months of age received a booster at 4 years of age.

Persistence of bactericidal antibodies following booster vaccination with 4CMenB at 12, 18 or 24months and immunogenicity of a fifth dose administered at 4years of age-a phase 3 extension to a randomised controlled trial.

Background: 4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24months and characterised the antibody response to a fifth dose administered at 4years of age.

Methods: A phase 3, open label, multi-centre extension to a randomised controlled trial conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four).

Mentoring in biostatistics: some suggestions for reform.

Mentoring is routinely used as a tool to facilitate acquisition of skills by new professionals in fields like medicine, nursing, surgery, and business. While mentoring has been proposed as an effective strategy for knowledge and skills transfer in biostatistics and related fields, there is still much to be done to facilitate adoption by stakeholders, including academia and employers of biostatisticians. This is especially troubling given that biostatisticians play a key role in the success or otherwise of clinical research conducted for evidence-based decisions.

Factors associated with discordance between absolute CD4 cell count and CD4 cell percentage in patients coinfected with HIV and hepatitis C virus.

Background: Liver cirrhosis has been associated with decreased absolute CD4 cell counts but preserved CD4 cell percentage in human immunodeficiency virus (HIV)-negative persons. We evaluated factors associated with discordance between the absolute CD4 cell count and the CD4 cell percentage in a cohort of patients coinfected with HIV and hepatitis C virus (HCV).

Methods: Baseline data from 908 participants in a prospective, Canadian, multisite cohort of individuals with HIV-HCV coinfection were analyzed.

Recovery-oriented service provision and clinical outcomes in assertive community treatment.

Objective: While the term "recovery" is routinely referenced in clinical services and health policy, few studies have examined the relationship between recovery-oriented service provision and client outcomes. The present study was designed to examine the relationship between recovery-orientation of service provision for persons with severe mental illnesses and outcomes in Assertive Community Treatment (ACT).

Methods: Client, family, staff, and manager ratings of service recovery-orientation and outcomes across a range of service utilization and community functioning indicators were examined among 67 ACT teams in Ontario, Canada.

Impact of hepatitis C viral replication on CD4+ T-lymphocyte progression in HIV-HCV coinfection before and after antiretroviral therapy.

Objective: HIV is known to have a negative impact on the progression of hepatitis C virus (HCV) infection, whereas the reverse remains unclear. We examined the impact of spontaneous clearance of HCV on CD4(+) T-lymphocyte count progression before and after initiation of antiretroviral therapy (ART) in HIV-HCV coinfected adults.

Methods: Data were analysed from participants in a Canadian, multisite prospective cohort of HIV-infected adults with serologic evidence of HCV infection.

Parenting-by-gender interactions in child psychopathology: attempting to address inconsistencies with a Canadian national database.

Background: Research has shown strong links between parenting and child psychopathology. The moderating role of child gender is of particular interest, due to gender differences in socialization history and in the prevalence of psychiatric disorders. Currently there is little agreement on how gender moderates the relationship between parenting and child psychopathology.

Tips on overlapping confidence intervals and univariate linear models.

In randomised controlled trials, an overlap of confidence intervals is often cited as evidence of 'no statistically significant difference' between intervention groups. This paper illustrates the limitations of this strategy and compares different univariate linear regression models with baseline and follow-up response measures. The researchers also demonstrate that using 'change in response' or exit score as a function of the baseline response in clinical studies leads to the same results.

Comparison of brachial and carotid artery ultrasound for assessing extent of subclinical atherosclerosis in HIV: a prospective cohort study.

Background: Non-invasive surrogate measures which are valid and responsive to change are needed to study cardiovascular risks in HIV. We compared the construct validity of two noninvasive arterial measures: carotid intima medial thickness (IMT), which measures anatomic disease; and brachial flow-mediated vasodilation (FMD), a measure of endothelial dysfunction.

Methods: A sample of 257 subjects aged 35 years or older, attending clinics in five Canadian centres, were prospectively recruited into a study of cardiovascular risk among HIV subjects.

Has the incidence of deep vein thrombosis in patients undergoing total hip/knee arthroplasty changed over time? A systematic review of randomized controlled trials.

Background: There is a perception in the orthopaedic and thromboembolism community that the incidence of deep vein thrombosis (DVT) has decreased in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA).

Objectives: To assess the incidence of DVT with warfarin thromboprophylaxis over time in patients undergoing elective TKA or THA.

Methods: The MEDLINE, EMBASE, and Cochrane Library databases were searched to October 2006, supplemented by a manual search of reference lists.

Quality of reporting of randomized controlled trials in general endocrinology literature.

Context: The reporting quality of randomized controlled trials (RCTs) is poor in general medicine and several areas of specialization but unknown in endocrinology.

Objective: Our aim was to assess the reporting quality of RCTs in general endocrinology. A secondary objective was to identify predictors for better reporting quality.

Comparison of generalized estimating equations and quadratic inference functions using data from the National Longitudinal Survey of Children and Youth (NLSCY) database.

Background: The generalized estimating equations (GEE) technique is often used in longitudinal data modeling, where investigators are interested in population-averaged effects of covariates on responses of interest. GEE involves specifying a model relating covariates to outcomes and a plausible correlation structure between responses at different time periods. While GEE parameter estimates are consistent irrespective of the true underlying correlation structure, the method has some limitations that include challenges with model selection due to lack of absolute goodness-of-fit tests to aid comparisons among several plausible models.