Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies target the underlying cause of cystic fibrosis (CF), and are generally well-tolerated; however, real-world studies indicate the frequency of discontinuation and adverse events (AEs) may be higher than what was observed in clinical trials. The objectives of this systematic review were to summarize real-world AEs reported for market-available CFTR modulators (i.e., ivacaftor (IVA), lumacaftor/ivacaftor (LUM/IVA), tezacaftor/ivacaftor (TEZ/IVA), and elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA)), and to identify ways in which the pharmacist on CF healthcare teams may contribute to mitigating and managing these AEs. The MEDLINE, EMBASE, CINAHL, and Web of Science Core Collection online databases were searched from 2012 to 1 Aug 2020. Full manuscripts or conference abstracts of observational studies, case series, and case reports were eligible for inclusion. The included full manuscripts and conference abstracts comprised of 54 observational studies, 5 case series, and 9 case reports. The types of AEs reported generally aligned with what have been observed in clinical trials. LUM/IVA was associated with a higher frequency of respiratory-related AE and discontinuation in real-world studies. A signal for mental health and neurocognitive AEs was identified with all 4 CFTR modulators. A systematic approach to monitoring for AEs in people with CF on CFTR modulators in the real-world setting is necessary to help better understand potential AEs, as well as patient characteristics that may be associated with higher risk of certain AEs. Pharmacists play a key role in the safe initiation and monitoring of people with CF on CFTR modulator therapies.

Background Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood. Objectives The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed. Methods MEDLINE (1946–3 May, 2017), EMBASE (1974–3 May, 2017), Pharmacogenomics Knowledge Base, and Public Health Genomics Knowledge Base online databases were searched. Studies were included if genotyping and analyses of phenytoin pharmacokinetics were performed in patients of the Middle East and North Africa region. Study quality was assessed using a National Institutes of Health assessment tool. A secondary search identified studies reporting genotypic and allelic frequencies of assessed genetic polymorphisms within the Middle East and North Africa region. Results Five studies met the inclusion criteria. CYP2C9, CYP2C19, and multidrug resistance protein 1 C3435T variants were evaluated. While CYP2C9*2 and *3 variants significantly reduced phenytoin metabolism, the impacts of CYP2C19*2 and *3 variants were unclear. The multidrug resistance protein 1 CC genotype was associated with drug-resistant epilepsy, but reported impacts on phenytoin pharmacokinetics were conflicting. Appreciable variability in minor allele frequencies existed both between and within countries of the Middle East and North Africa region. Conclusions CYP2C9 decrease-of-function alleles altered phenytoin pharmacokinetics in patients originating from the Middle East and North Africa region. The impacts of CYP2C19 and multidrug resistance protein 1 C3435T variants on phenytoin pharmacokinetic and clinical outcomes are unclear and require further investigation. Future research should focus on the clinical outcomes associated with phenytoin therapy. PROSPERO 2017: CRD42017057850

The mental health effects of elexacaftor/tezacaftor/ivacaftor (ETI) on adults with CF are still uncertain with mixed findings from published studies. To systematically investigate the impact of ETI on symptoms of anxiety and depression in adults with CF, Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire (PHQ-9) scores were evaluated at baseline, 6 months, and 12 months post-ETI. Overall, GAD-7 and PHQ-9 scores improved at 6 months post-ETI, with a greater proportion of individuals experiencing a clinically significant improvement (vs. worsening) of their symptoms, which was sustained at 12 months. Factors influencing mental health outcomes included pre-existing psychiatric diagnoses and psychiatric medication use. In conclusion, although there was overall improvement in anxiety and depression symptoms post-ETI, approximately 10 % of individuals experienced clinically significant worsening.

Evaluation of pre-licensure students’ competency in team-based decision-making is lacking. The purposes of this study were to evaluate pre-licensure pharmacy students’ competency in team-based decision-making in the context of an objective structured clinical examination (OSCE), and to determine whether performance correlated with reflective assignment scores. Students’ self-assessment and conceptualization of team-based decision-making in practice was also evaluated. Twenty-three pre-licensure pharmacy students’ competency in team-based decision-making was evaluated in an OSCE station and with a reflective journal assignment; rubric scores for both evaluations were compared using Spearman’s rank order analysis. Students completed an 18-item questionnaire regarding attitudes, confidence, and perceptions related to team-based decision-making. Descriptive statistics and construct analysis with open coding were used to analyse questionnaire results. Mean OSCE station and reflective journal scores were 45% and 66.3%, respectively, and were not correlated. Students’ attitudes toward team-based decision-making were positive, and they reported performing associated behaviours during experiential education rotations. Students appropriately defined ‘team-based decision-making’ and were highly confident in performing related activities. However, students’ conceptualization of team-based decision-making did not align with the pharmacy program’s competency framework. Three key themes were identified through the study analyses: 1) student performance is dependent on assessment context when evaluating collaborator-related competencies; 2) there is a mismatch between students’ perceived competency and objectively measured competence when collaborator outcomes were assessed within an OSCE; and 3) students’ perceptions of team-based decision-making do not align with the program’s competency framework. Future research is necessary to assess competency and perceptions of team-based decision-making in students from other healthcare professions, and to further evaluate whether pre-licensure students are “collaborative practice ready”. Article Type: Case Study