Characterisation of pharmacokinetics, safety and tolerability in a first-in-human study for AZD8154, a novel inhaled selective PI3Kγδ dual inhibitor targeting airway inflammatory disease.

AIMS: This 3-part, randomised, phase 1 first-in-human study (NCT03436316) investigated the safety, tolerability and pharmacokinetics (PK) of AZD8154, a dual phosphoinositide 3-kinase (PI3K) γδ inhibitor developed as a novel inhaled anti-inflammatory treatment for respiratory disease. METHODS: Healthy men, and women of nonchildbearing potential, were enrolled to receive single and multiple ascending inhaled doses of AZD8154 in parts 1 and 3 of the study, respectively, while part 2 characterised the systemic PK after a single intravenous (IV) dose. In part 1, participants received 0.1-7.7 mg AZD8154 in 6 cohorts. In part 2, participants were given 0.15 mg AZD8154 as an IV infusion. In part 3, AZD8154 was given in 3 cohorts of 0.6, 1.8 and 3.1 mg, with a single dose on Day 1 followed by repeated once-daily doses on Days 4-12. RESULTS: In total, 78 volunteers were randomised. All single inhaled, single IV and multiple inhaled doses were shown to be well tolerated without any safety concerns. A population PK model, using nonlinear mixed-effect modelling, was developed to describe the PK of AZD8154. The terminal mean half-life of AZD8154 was 18.0-32.0 hours. The geometric mean of the absolute pulmonary bioavailability of AZD8154 via the inhaled route was 94.1%. CONCLUSION: AZD8154 demonstrated an acceptable safety profile, with no reports of serious adverse events and no clinically significant drug-associated safety concerns reported in healthy volunteers. AZD8154 demonstrated prolonged lung retention and a half-life supporting once-daily dosing.

School Nurses' Experiences Working With Students With Mental Health Problems: A Qualitative Study.

The aim was to describe school nurses' experiences working with students with mental health problems. In this inductive qualitative study, interviews were conducted with 14 school nurses in Sweden. The content analysis revealed three themes: (1) sense of worriedness about working with students with mental health problems, (2) taking care of students with mental health issues was an opportunity for personal and professional development, and (3) the experience of making a difference for young people with mental health problems. The school nurses working with students who have mental health problems had to cope with their own emotions, worries, and feelings of insufficiency. However, the school nurses also found the work to be meaningful and rewarding because they appreciated the opportunity for personal and professional development while taking care of students with mental health problems. They felt grateful for having a profession that had a huge impact on children's/adolescents' lives.

Discrepancies between the electronic medical record, the prescriptions in the Swedish national prescription repository and the current medication reported by patients.

PURPOSE: To study discrepancies between (i) the prescribed current treatment stated by patients with congestive heart failure (CHF) compared with patients with other chronic diseases, (ii) the data in the medication list (ML) in the electronic medical record and (iii) the data in the prescription list (PL) on the prescriptions stored in the national prescription repository in Sweden, to determine current, noncurrent, duplicate and missing prescriptions. METHODS: At one healthcare centre, a random sample of patients 18 years and older with a diagnosis of CHF, diabetes mellitus (DM) or osteoarthritis (OA) provided written informed consent to participate. Participants were interviewed by telephone on the prescribed current treatment. RESULTS: Of 161 invited patients (61 CHF, 50 DM and 50 OA), 66 patients were included. More than 80% of the patients had at least one discrepancy, a noncurrent, a duplicate or a missing prescription, in the ML and PL. The overall congruence for unique prescriptions on current treatment between the ML and the PL was only 55%. Patients with CHF had overall more discrepancies and patients with DM fewer discrepancies in the ML. CONCLUSIONS: Prescriptions for noncurrent treatment, duplicates and missing prescriptions are common in both the ML in the electronic medical record and the list on prescriptions stored in the Swedish National Prescription Repository. Patients with CHF had more discrepancies in the ML. The risk for medication errors in primary care due to incorrect information on prescribed treatment may be substantial.