KCNT1 (K⁺ channel subfamily T member 1) is a sodium-activated potassium channel highly expressed in the nervous system which regulates neuronal excitability by contributing to the resting membrane potential and hyperpolarisation following a train of action potentials. Gain of function mutations in the KCNT1 gene are the cause of neurological disorders associated with different forms of epilepsy. To gain insights into the underlying pathobiology we investigated the functional effects of 9 recently published KCNT1 mutations, 4 previously studied KCNT1 mutations, and one previously unpublished KCNT1 variant of unknown significance. We analysed the properties of KCNT1 potassium currents and attempted to find a correlation between the changes in KCNT1 characteristics due to the mutations and severity of the neurological disorder they cause. KCNT1 mutations identified in patients with epilepsy were introduced into the full length human KCNT1 cDNA using quick-change site-directed mutagenesis protocol. Electrophysiological properties of different KCNT1 constructs were investigated using a heterologous expression system (HEK293T cells) and patch clamping. All mutations studied, except T314A, increased the amplitude of KCNT1 currents, and some mutations shifted the voltage dependence of KCNT1 open probability, increasing the proportion of channels open at the resting membrane potential. The T314A mutation did not affect KCNT1 current amplitude but abolished its voltage dependence. We observed a positive correlation between the severity of the neurological disorder and the KCNT1 channel open probability at resting membrane potential. This suggests that gain of function KCNT1 mutations cause epilepsy by increasing resting potassium conductance and suppressing the activity of inhibitory neurons. A reduction in action potential firing in inhibitory neurons due to excessively high resting potassium conductance leads to disinhibition of neural circuits, hyperexcitability and seizures.

Clinical implementation of pharmacogenomic (PGx)‐guided prescribing in oncology lags behind research evidence generation. We aimed to identify healthcare professionals' (HCPs) and consumers' knowledge, attitudes, perspectives, and education needs to inform strategies for implementation of scalable and sustainable oncology PGx programs. Systematic review of original articles indexed in EMBASE, EMCARE, MEDLINE, and PsycInfo from January 2012 until June 2022, following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines and using the Mixed Methods Appraisal Tool. PROSPERO registration number CRD42022352348. Of 1442 identified studies; 23 met inclusion criteria with 87% assessed high quality. Of these, 52% reported on HCPs, 35% on consumers, and 13% on both HCPs and consumers. Most were conducted in the United States (70%) and included multiple cancer types (74%). Across studies, HCPs and consumers mostly perceived value in PGx, however, both groups reported barriers to utilization, including cost, lack of consistent recommendations across guidelines, and limited knowledge among HCPs; test accuracy, clear testing benefits, and genomic information confidentiality among consumers. HCPs and consumers value and want to engage in PGx strategies in oncology care, however, are inhibited by unmet needs and practice and knowledge gaps. Implementation strategies aimed at addressing these issues may best support increased PGx uptake in oncology practice.

The accuracy of diagnostic laboratory tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can impact downstream clinical procedures in managing and controlling the outbreak of coronavirus disease 2019 (COVID-19). To assess the effectiveness of laboratory tools for managing COVID-19 patients in low-income countries (LICs), we systematically searched the PubMed, Embase, Scopus and CINHAL databases for reports published between January 2020 and June 2022. We found that 22 of 1303 articles reported the performance of various SARS-CoV-2 detection tools across 10 LICs. These tools were (1) real-time reverse transcriptase polymerase chain reaction (RT-PCR); (2) reverse transcription loop-mediated isothermal amplification (RT-LAMP); (3) rapid diagnostic tests (RDTs); (4) enzyme-linked immunosorbent assay (ELISA); and (5) dot-blot immunoassay. The detection of COVID-19 is largely divided into two main streams—direct virus (antigen) detection and serology (immunoglobulin)-based detection. Point-of-care testing using antigen-based RDTs is preferred in LICs because of cost effectiveness and simplicity in the test procedures. The nucleic acid amplification technology (RT-PCR and RT-LAMP) has the highest diagnostic performance among the available tests, but it is not broadly used in this context due to costs and shortage of facilities/trained staff. The serology-based test method is affected by antibody interferences and varying amounts of SARS-CoV-2 immunoglobulins expressed at different stages of disease onset. We further discuss the effectiveness and shortcomings of each of these tools in the diagnosis and management of COVID-19. Using the LICs as the study model, our findings highlight ways to improve the quality and turnaround time of COVID-19 testing in resource-constrained settings, notably through local/international collaborative efforts to refine the molecular-based or immunoassay-based testing technologies.

Background: Glucagon-like peptide 1 (GLP-1) analogues are a class of medications that stimulate glucose-dependent insulin release and slow gastric emptying. With the increasing use of GLP-1 analogues, concerns about potential psychiatric adverse events (AEs) remain under-explored. Aim: This pharmacovigilance study aimed to investigate the prevalence of psychiatric AEs associated with currently available GLP-1 analogues by analysing publicly available national datasets from the US (FAERS), Canada (CVAROD) and Australia (DAEN). Method: Psychiatric AE reports were extracted from all three databases for all approved GLP-1 analogues. A disproportionality analysis was conducted to calculate reporting odds ratios (RORs) and 95% confidence intervals (CIs) for psychiatric AEs of interest. Results: Significant associations were identified when multiple databases reported elevated RORs. Semaglutide was associated with depressive symptoms (FAERS, ROR = 6.24 CI 4.49–8.69), panic attacks (FAERS, ROR = 1.46 CI 1.16–1.82) and suicidal ideation (FAERS, ROR = 2.58 CI 2.31–2.88). Liraglutide was linked to depression (CVAROD, ROR = 1.68 CI 1.12–2.51), while dulaglutide showed positive associations with eating disorders (FAERS, ROR = 1.47 CI 1.26–1.71) and insomnia (FAERS, ROR = 2.93 CI 2.35–3.66). Conclusion: GLP-1 analogues, particularly semaglutide and liraglutide, are associated with significant psychiatric AEs, especially depression and suicidal ideation. Further studies are required to understand the mechanisms underlying these associations, particularly in patients with pre-existing psychiatric conditions.

Objectives: Dynamic and adaptive services that provide timely access to care are pivotal to ensuring patients with palliative needs experience high-quality care. Patients who have palliative care needs may require symptomatic relief with medicines and, therefore, may engage with community pharmacists frequently. However, there is limited evidence for pharmacists’ involvement in community palliative care models. Therefore, a scoping review was conducted to identify pharmacists’ role in community palliative care. Methods: A systematic search strategy was implemented across PubMed, PsychINFO, CINAHL, and Embase databases. Articles were screened by abstract and full text against inclusion and exclusion criteria. Key findings: Five articles (two from Australia, two from England, and one from Scotland) met the inclusion criteria and described interventions involving pharmacists in community palliative care. This review has identified that the inclusion of trained pharmacists in community palliative care teams can improve the quality of care provided for patients with palliative needs. Pharmacists are able to undertake medication reviews and provide education to patients and other healthcare professionals on the quality use of palliative care medicines. Additionally, the underutilization of community pharmacists in palliative care, the need for further training of pharmacists, and improved community pharmacy access to patient information to deliver community palliative care were identified. Conclusion: Pharmacists can play a vital role in community palliative care to enhance the quality of life of patients. There is a need for greater pharmacist education/training, improved interprofessional communication, improved access to patient information and sustainable funding to strengthen community-based palliative care.

Cultural competence is instrumental in reducing health equities. Addressing cultural competence at higher education level in healthcare students lays a solid cultural competence foundation for professional practice. The use of vignettes as a teaching intervention was effective because it allowed the use of role-modelling in real-life situations. The study aimed to enhance cultural competence in undergraduate pharmacy students using a self-directed online interactive cultural competence module embedded with three vignettes (case scenarios). This study was an exploratory longitudinal mixed method (survey and written feedback) study and used a convenience sample of 90 pharmacy students at an Australian University. Students’ self-perceived transcultural self-efficacy was evaluated pre- and post-intervention using Jeffreys’ Transcultural Self-Efficacy Tool (TSET) which is a validated outcome measure. Vignettes were effective in teaching cultural competence as shown by significant (P < 0.0005) changes pre- to post-intervention in cognitive, practical and affective domains scores using TSET. The affective domain had the least positive mean score change. There was no significant association between any of the demographic factors such as age, gender or birthplace/parents’ birthplace and changes in any of the three domains. Cronbach’s alpha of >0.90 in all domains confirmed the test’s internal consistency and reliability. The findings were indicative of the students’ positive receptivity to learning cultural competence and that they had a well-developed understanding of cultural competence. Further research is needed to determine why most cultural competence teaching methods produce little or no meaningful change in enhancing the affective domain.