Role of the endocannabinoid system in fragile X syndrome: potential mechanisms for benefit from cannabidiol treatment.

Multiple lines of evidence suggest a central role for the endocannabinoid system (ECS) in the neuronal development and cognitive function and in the pathogenesis of fragile X syndrome (FXS). This review describes the ECS, its role in the central nervous system, how it is dysregulated in FXS, and the potential role of cannabidiol as a treatment for FXS. FXS is caused by deficiency or absence of the fragile X messenger ribonucleoprotein 1 (FMR1) protein, FMRP, typically due to the presence of >200 cytosine, guanine, guanine sequence repeats leading to methylation of the FMR1 gene promoter.

A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX).

Background: Fragile X syndrome (FXS) is associated with dysregulated endocannabinoid signaling and may therefore respond to cannabidiol therapy.

Design: CONNECT-FX was a double-blind, randomized phase 3 trial assessing efficacy and safety of ZYN002, transdermal cannabidiol gel, for the treatment of behavioral symptoms in children and adolescents with FXS.

Methods: Patients were randomized to 12 weeks of ZYN002 (250 mg or 500 mg daily [weight-based]) or placebo, as add-on to standard of care.

Causal cascade of direct and indirect effects of anifrolumab on patient-reported outcomes: structural equation modelling of two Phase 3 trials.

Objectives: SLE significantly impairs health-related quality of life (HRQoL). In this post hoc analysis, structural equation modelling was used to examine the 'causal cascade' of interaction between anifrolumab, disease activity and patient-reported outcomes (PROs) in pooled data from the phase 3 TULIP-1 and TULIP-2 trials.

Methods: Data were pooled from the TULIP-1 (n = 364) and TULIP-2 (n = 362) randomized, placebo-controlled, 52-week trials of intravenous anifrolumab (300 mg every 4 weeks for 48 weeks).

Clinical meaningfulness of a British Isles Lupus Assessment Group-based Composite Lupus Assessment response in terms of patient-reported outcomes in moderate to severe systemic lupus erythematosus: a post-hoc analysis of the phase 3 TULIP-1 and TULIP-2 trials of anifrolumab.

Background: The British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) is a validated global measure of treatment response in systemic lupus erythematosus (SLE) clinical trials but does not include patient-reported outcomes. To evaluate the clinical meaningfulness of a BICLA response from the patient perspective, we aimed to analyse patient-reported outcomes by BICLA responses with anifrolumab or placebo in patients with moderate to severe SLE.

Methods: We did a post-hoc analysis of pooled data from the phase 3 TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) trials of anifrolumab, which assessed health-related quality of life using the Short Form 36 Health Survey (SF-36; version 2) and Lupus Quality of Life, fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), pain using the Numerical Rating Scale, and disease activity using Patient Global Assessment.

Measuring the patient experience of chronic rhinosinusitis with nasal polyposis: qualitative development of a novel symptom diary.

Background: This qualitative study assessed the experience of patients with chronic rhinosinusitis with nasal polyposis (NP) to inform the development of a novel symptom diary for clinical study use.

Methods: Concept elicitation and cognitive interviews were conducted with patients who had a physician-verified diagnosis of NP and a history of intranasal corticosteroid use. Concepts were identified via open-ended and follow-up questions.

Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD): Measurement Properties of Novel Patient-Reported Symptom Measures.

Background: The Asthma Daytime Symptom Diary (ADSD) and the Asthma Nighttime Symptom Diary (ANSD) were developed to meet the need for standardized patient-reported measures of asthma symptoms to assess treatment trial outcomes in adults and adolescents.

Objective: To determine scoring and evaluate the measurement properties of the ADSD/ANSD.

Methods: Adolescents (12-17 years) and adults (18+ years) with asthma completed draft 8-item electronic versions of the ADSD/ANSD for 10 days alongside the Adult Asthma Symptom Daily Scales (AASDS) and a Patient Global Impression of Severity (PGIS).

Development and content validation of a symptom assessment for eosinophilic gastritis and eosinophilic gastroenteritis in adults and adolescents.

Background: A patient reported outcome (PRO) instrument with evidence of validity and reliability for assessing symptoms of eosinophilic gastritis (EG) and eosinophilic gastroenteritis (EGE) is needed to measure treatment benefit in clinical trials. The aim of this research is to develop an EG/EGE symptom PRO instrument for patients aged 12 and above.

Methods: The Symptom Assessment for Gastrointestinal Eosinophilic Diseases (SAGED) was developed through a literature review, discussions with expert clinicians, and concept elicitation and cognitive debriefing interviews with patients.

Differing perceptions of asthma control and treatment effectiveness by patients with severe asthma and treating subspecialists in the United States.

Objective: For patients with severe asthma (SA), overestimation of asthma control may lead to poorer outcomes. The objective of this study was to assess concurrent patient and specialist assessments of asthma control and treatment effectiveness among a large US cohort of SA patients.

Methods: CHRONICLE is an ongoing observational study of patients with SA treated by US subspecialists.

Health-Related Quality of Life and Productivity Among US Patients with Severe Asthma.

Background: Health-related quality of life (HRQoL) and productivity of patients with confirmed severe asthma (SA) have not been well characterized in large, real-world populations.

Purpose: To characterize SA impact on HRQoL, work productivity, and activity impairment in a large, real-world cohort in the United States (US).

Methods: CHRONICLE is an observational study of specialist-treated adults (≥18 years) in the US with SA receiving biologics or maintenance systemic corticosteroids (mSCS), or those persistently uncontrolled by high-dosage inhaled corticosteroids with additional controllers (HD ICS+).

Health-related quality of life with tralokinumab in moderate-to-severe atopic dermatitis: A phase 2b randomized study.

Background: Atopic dermatitis (AD) is associated with a substantial burden on quality of life (QoL).

Objective: To evaluate the effects of tralokinumab on health-related QoL in patients with moderate-to-severe AD using patient-reported outcomes.

Methods: This was a phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study in adults with moderate-to-severe AD.

Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY.

Background: Patients with severe, uncontrolled asthma experience frequent exacerbations and hospitalization, leading to poor health-related quality of life. In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced exacerbations by up to 71% and improved lung function, asthma control, and health-related quality of life vs placebo.

Objective: This analysis further assessed the impact of tezepelumab on patient-reported outcomes (PROs) in PATHWAY.

Benralizumab for the Prevention of COPD Exacerbations.

Background: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.

Methods: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. <220 per cubic millimeter]) who had frequent exacerbations despite receiving guideline-based inhaled treatment.

Daily patient-reported health status assessment improvements with benralizumab for patients with severe, uncontrolled eosinophilic asthma.

Background: Patients with severe, uncontrolled asthma experience debilitating symptoms that result in meaningful reductions to health-related quality of life. Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody that reduces exacerbations and improves asthma symptoms for patients with severe, uncontrolled eosinophilic asthma.

Objective: The objective of this study was to evaluate improvements in daily asthma-related health status outcomes following treatment with benralizumab.

Evaluation of a respiratory symptom diary for clinical studies of idiopathic pulmonary fibrosis.

Background: There are no validated patient diaries for evaluating respiratory symptoms in idiopathic pulmonary fibrosis (IPF).

Purpose: To evaluate the performance properties of the chronic obstructive pulmonary disease (COPD) Evaluating Respiratory Symptoms™ (E-RS™: COPD) measure in patients with IPF.

Methods: Concept elicitation and cognitive interviews were conducted with IPF patients to evaluate content validity, including comprehensiveness, relevance, and interpretability of E-RS™ items in this patient population.

The development, implementation and evaluation of clinical pathways for chronic obstructive pulmonary disease (COPD) in Saskatchewan: protocol for an interrupted times series evaluation.

Background: Chronic obstructive pulmonary disease (COPD) has substantial economic and human costs; it is expected to be the third leading cause of death worldwide by 2030. To minimize these costs high quality guidelines have been developed. However, guidelines alone rarely result in meaningful change.

An overview of biosimilars and non-biologic complex drugs in Europe, the United States, and Canada and their relevance to multiple sclerosis.

The advent of biological medicines has significantly transformed the landscapes of many disease spaces and improved the lives of millions around the world. However, the structural complexity and sensitivity of such products result in a high price tag, adding to already financially strained healthcare systems. As these and other expensive complex drugs lose market exclusivity, stakeholders eagerly await the arrival of lower cost alternatives, such as biosimilars and subsequent entry non-biological complex drugs (NBCDs).

Development of the chronic obstructive pulmonary disease morning symptom diary (COPD-MSD).

Background: The morning tends to be the most difficult time of day for many patients with chronic obstructive pulmonary disease (COPD) when symptoms can limit one's ability to perform even simple activities. Morning symptoms have been linked to higher levels of work absenteeism, thereby increasing the already substantial economic burden associated with COPD. A validated patient-reported outcome (PRO) instrument designed to capture morning symptoms will allow for a more comprehensive approach to the evaluation of treatment benefit in COPD clinical trials.

Idiopathic Pulmonary Fibrosis in United States Automated Claims. Incidence, Prevalence, and Algorithm Validation.

Rationale: Estimates of idiopathic pulmonary fibrosis (IPF) incidence and prevalence from electronic databases without case validation may be inaccurate.

Objectives: Develop claims algorithms to identify IPF and assess their positive predictive value (PPV) to estimate incidence and prevalence in the United States.

Methods: We developed three algorithms to identify IPF cases in the HealthCore Integrated Research Database.

A new measure of caregiver burden in Alzheimer's disease: the caregiver-perceived burden questionnaire.

Objective: To validate the Caregiver-Perceived Burden Questionnaire (CPBQ) and report its psychometric properties.

Methods: The CPBQ was administered to caregivers of patients with moderate-to-severe AD in a double-blind randomized trial comparing extended-release memantine to placebo (n = 676). Measurement properties were analyzed using factor analysis, classical test theory, and Rasch analysis.

Pain-free results with sumatriptan taken at the first sign of migraine pain: 2 randomized, double-blind, placebo-controlled studies.

Objective: To evaluate the efficacy and tolerability of sumatriptan, 50-mg and 100-mg tablets, compared with placebo for treatment of migraine at the first sign of pain.

Patients And Methods: Two identical multicenter randomized, double-blind, placebo-controlled, single-attack studies were conducted from May through November 2000 in adults (aged 18-65 years). Patients treated migraine at the first sign of pain, while pain was mild, but not more than 2 hours after onset with oral sumatriptan, 50 mg or 100 mg, or matching placebo.

The pharmacokinetics of sumatriptan when administered with clarithromycin in healthy volunteers.

Background: Macrolide antibiotics such as clarithromycin are potent inhibitors of the cytochrome P450 (CYP)3A4 isozyme and have the potential to attenuate the metabolism and increase blood concentrations of drugs metabolized by this pathway. In vitro studies have suggested that sumatriptan is metabolized primarily by the monoamine oxidase-A isozyme and not by CYP3A4.

Objective: This study sought to determine the effect of coadministration of clarithromycin dosed to steady state on the pharmacokinetics of a single dose of sumatriptan.

Sumatriptan nasal spray and cognitive function during migraine: results of an open-label study.

Objective: To examine measures of cognitive function during acute migraine, before and after treatment with sumatriptan nasal spray, 20 mg.

Background: Migraineurs frequently report symptoms of cognitive impairment during migraine. The efficacy of sumatriptan for treatment of migraine-related cognitive impairment is undocumented.