HF-rTMS treatment decreases psychomotor retardation in medication-resistant melancholic depression

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Modelling Forced Vital Capacity in Idiopathic Pulmonary Fibrosis: Optimising Trial Design

Introduction: Forced vital capacity is the only registrational endpoint in idiopathic pulmonary fibrosis clinical trials. As most new treatments will be administered on top of standard of care, estimating treatment response will become more challenging. We developed a simulation model to quantify variability associated with forced vital capacity decline. Methods: The model is based on publicly available clinical trial summary and home spirometry data. A single, illustrative trial setting is reported. Model assumptions are 400 subjects randomised 1:1 to investigational drug or placebo over 52 weeks, 50% of each group receiving standard of care (all-comer population), and a 90-mL treatment difference in annual forced vital capacity decline. Longitudinal profiles were simulated and the impact of varying clinical scenarios evaluated. Results: Power to detect a significant treatment differe

Self-reported alcohol, tobacco, and cannabis use during covid-19 lockdown measures: results from a web-based survey.

BACKGROUND: The outbreak of coronavirus disease 19 (COVID-19) has led to measures of social distancing and quarantine worldwide. This stressful period may lead to psychological problems, including increases in substance use. OBJECTIVE: To investigate changes in alcohol, tobacco, and cannabis consumption before and during COVID-19 lockdown and motives for these changes in substance use. METHOD: A web-based survey was filled out by an unselected population during the social distancing measures of the COVID-19 pandemic in Belgium that assessed changes in alcohol, tobacco, and cannabis consumption in the period before and during the COVID-19 lockdown and also asked about reasons for change. RESULTS: A total of 3,632 respondents (mean age 42.1 ± 14.6 years; 70% female) filled out the survey. Overall, respondents reported consuming more alcohol (d = 0.21) and smoking more cigarettes (d = 0.13) than before the COVID-19 pandemic (both p < 0.001), while no significant changes in the consumption of cannabis were noted. The odds of consuming more alcohol during the lockdown were associated with younger age (OR = 0.981, p < 0.001), more children at home (OR = 1.220, p < 0.001), non-healthcare workers (p < 0.001), and being technically unemployed related to COVID-19 (p = 0.037). The odds of smoking more cigarettes during the lockdown were associated with younger age (OR = 0.988, p = 0.027), current living situation (p < 0.001), lower education (p = 0.015), and working situation related to COVID-19 (p = 0.018). Boredom, lack of social contacts, loss of daily structure, reward after a hard-working day, loneliness, and conviviality were the main reasons for consuming more of the various substances. CONCLUSIONS: During the lockdown, individuals consumed slightly more alcohol and smoked marginally more cigarettes compared to the period before the lockdown. Further research focussing on follow-up of individuals at risk may be useful to provide appropriate care in post-COVID times

Modelling Forced Vital Capacity in Idiopathic Pulmonary Fibrosis: Optimising Trial Design

INTRODUCTION: Forced vital capacity is the only registrational endpoint in idiopathic pulmonary fibrosis clinical trials. As most new treatments will be administered on top of standard of care, estimating treatment response will become more challenging. We developed a simulation model to quantify variability associated with forced vital capacity decline. METHODS: The model is based on publicly available clinical trial summary and home spirometry data. A single, illustrative trial setting is reported. Model assumptions are 400 subjects randomised 1:1 to investigational drug or placebo over 52 weeks, 50% of each group receiving standard of care (all-comer population), and a 90-mL treatment difference in annual forced vital capacity decline. Longitudinal profiles were simulated and the impact of varying clinical scenarios evaluated. RESULTS: Power to detect a significant treatment difference was 87-97%, depending on the analysis method. Repeated measures analysis generally outperformed analysis of covariance and mixed linear models, particularly with missing data (as simulated data were non-linear). A 15% yearly random dropout rate led to 0.6-5% power loss. Forced vital capacity decline-related dropout introduced greater power loss (up to 12%), as did subjects starting/stopping standard of care or investigational drug. Power was substantially lower for a 26-week trial due to the smaller assumed treatment effect at week 26 (sample size would need doubling to reach a power similar to that of a 52-week trial). CONCLUSIONS: Our model quantifies forced vital capacity decline and associated variability, with all the caveats of background therapy, permitting robust power calculations to inform future idiopathic pulmonary fibrosis clinical trial design. FUNDING: Galapagos NV (Mechelen, Belgium).status: publishe