A repeat-dose thorough QT study of inhaled fluticasone furoate/vilanterol combination in healthy subjects

AIMS

This study was designed as a thorough QT (TQT) study to evaluate the effects of fluticasone furoate(FF)/vilanterol (VI) in healthy subjects. Supportive data from a TQT study conducted with FF are also presented.

METHODS

This was a randomized, placebo-and positive-controlled, double-dummy, double-blind, four-way crossover study, in which healthy subjects (n = 85) were randomized to 7 days of once-daily treatment of FF/VI (200/25 or 800/100 μg) or placebo or single-dose oral moxifloxacin (single-blind, 400 mg). In the supportive TQT study, subjects (n = 40) were randomized to single-dose inhaled FF(4000 μg), oral moxifloxacin (400 mg) or placebo.

RESULTS

There was a lack of effect of FF/VI (200/25 μg) on QTcF (Fridericia''s correction); all time-matched mean differences from baseline relative to placebo (0–24 h) were <5 ms, with upper 90% confidence intervals (CI) of <10 ms. At 800/100 μg, FF/VI had no significant clinicaleffect on QTcF except at 30 min postdose when the 90% CI was >10 ms [mean (90% CI), 9.6 ms (7.2, 12.0)]. No effect on QTci (individually corrected) was observed at either strength of FF/VI, with mean time-matched treatment differences <5 ms at all time points [upper 90% CIs <10 ms (0–24 h)]. Assay sensitivity was confirmed; moxifloxacin prolonged QTcF and QTci, with time-matched mean differences from baseline relative toplacebo of >10 ms (1–8 h postdose).

CONCLUSIONS

Repeat once-daily dosing of FF/VI (200/25 μg), which is the highest therapeutic strength used in phase III studies, is not associated with QTc prolongation in healthy subjects. Supratherapeutic strength FF/VI (800/100 μg) demonstrated a small transient effect on QTcF but not on QTci.     

Sewage‐based epidemiology in monitoring the use of new psychoactive substances: Validation and application of an analytical method using LC‐MS/MS

Sewage‐based epidemiology (SBE) employs the analysis of sewage to detect and quantify drug use within a community. While SBE has been applied repeatedly for the estimation of classical illicit drugs, only few studies investigated new psychoactive substances (NPS). These compounds mimic effects of illicit drugs by introducing slight modifications to chemical structures of controlled illicit drugs. We describe the optimization, validation, and application of an analytical method using liquid chromatography coupled to positive electrospray tandem mass spectrometry (LC‐ESI‐MS/MS) for the determination of seven NPS in sewage: methoxetamine (MXE), butylone, ethylone, methylone, methiopropamine (MPA), 4‐methoxymethamphetamine (PMMA), and 4‐methoxyamphetamine (PMA). Sample preparation was performed using solid‐phase extraction (SPE) with Oasis MCX cartridges. The LC separation was done with a HILIC (150 x 3 mm, 5 µm) column which ensured good resolution of the analytes with a total run time of 19 min. The lower limit of quantification (LLOQ) was between 0.5 and 5 ng/L for all compounds. The method was validated by evaluating the following parameters: sensitivity, selectivity, linearity, accuracy, precision, recoveries and matrix effects. The method was applied on sewage samples collected from sewage treatment plants in Belgium and Switzerland in which all investigated compounds were detected, except MPA and PMA. Furthermore, a consistent presence of MXE has been observed in most of the sewage samples at levels higher than LLOQ. Copyright © 2015 John Wiley & Sons, Ltd.     

Research strategy for health sciences: Facebook friend request is non‐differentially accepted in a diverse,young adult population

Social media is being used for recruitment and the study of health‐care choices and behavior, and could be particularly helpful to reach young adult populations outside of a 4 year college setting. The aim of this study was to report on overall success of recruiting young adults in diverse settings with respect to education and employment into a study using Facebook (FB). Young adults (n = 380, 50% male, 44% white) who had been involved in a longitudinal research project received a friend request from the research study group's profile. Acceptance rates of friend requests and sociodemographic and mental health factors associated with acceptance were evaluated. Approximately 67% of 318 participants who received a friend request accepted the request. Sociodemographic and mental health characteristics were similar between those who did and did not accept friend requests, suggesting non‐differential recruitment through FB. Friending through FB is a feasible way to reach young adults involved in health and behavioral research, and could be a way to expand the populations that are studied in health science research to maximize generalizability of the conclusions drawn.     

The transition from patient to mental health peer worker: A grounded theory approach

Peer workers are increasingly being engaged in contemporary mental healthcare. To become a peer worker, patients must evolve from having a patient identity to a peer worker identity. This study aims to understand how mental health peer workers experience their transition and how it affects their view of themselves and their direct working context. A grounded theory approach was used. Seventeen mental health peer workers in Belgium were recruited through theoretical sampling. Semi‐structured interviews were conducted and analysed according to the constant comparative method. The results indicate that novice peer workers experience peer work as an opportunity to liberate themselves from the process of mental suffering and realise an acceptable form of personal self‐maintenance. As peer workers become more experienced, they are confronted with external factors that influence their self‐maintenance and personal development. Experiencing clarity in their duties and responsibilities, equality, and transparency in the workplace reinforce their experience of self‐maintenance and positively influence their self‐development. Experiencing a lack of clarity in their duties and responsibilities, inequality, and lack of openness discourage peer workers’ self‐development process. These experiences challenge their personal motivations to become peer workers, which are usually linked to building a meaningful life for themselves. The insights can encourage organisations to build up a supportive environment collaboratively with peer workers and ensure that peer workers can exert their authentically unique role in mental healthcare.