The short version of students' perceptions of interprofessional clinical education-revised (SPICE-R3): a confirmatory factor analysis.

The Students' Perceptions of Physician-Pharmacist Interprofessional Clinical Education and its revision (SPICE, SPICE-R) were designed to understand medicine and pharmacy students' perceptions of interprofessional education and collaborative practice in managing complex health problems. The SPICE-R authors, however, suggested for additional items for subscales "roles and responsibilities for collaborative care" and "patient outcomes from collaborative practice". We added two items and introduced SPICE-R3 to differentiate it from the 10-item SPICE-R2 and to adapt the scale to a wider range of healthcare members. We administered the SPICE-R3 to healthcare students at the height of the COVID-19 outbreak in Hong Kong in February 2020. Using data from 225 students from Chinese medicine, medicine, nursing, and pharmacy, confirmatory factor analysis indicated nine items having acceptable item coefficients. Our data obtained a good fit to the three-factor, nine-item model suggesting construct validity. Results of the between-network analysis suggest that the three subscales of SPICE-R3 correlated systematically with other theoretically relevant variables in the nomological network suggesting convergent validity. The SPICE-R3 is a valid measure to examine Hong Kong healthcare students' interprofessional attitudes in online interprofessional education even during the pandemic. Implications and directions for future research are provided.

Development of an HPLC/UV method for the evaluation of extractables and leachables in plastic: Application to a plastic-packaged calcium gluconate glucoheptonate solution.

Calcium gluconate glucoheptonate (GGCa) is known to interact with glass containers, leading to the leaching of aluminum from the glass into the solution at toxic level. Therefore, plastic containers seem to be a preferable packaging alternative. Nevertheless, plastics contain potentially toxic additives which could be released into the solution. In order to study content container interaction between GGCa and two plastic containers (polypropylene PP and polyethylene PE containers), an HPLC-PDA method was developed to separate, detect and quantify eleven additives commonly found in plastic materials, with good limit of detection and quantification. This method was then applied to evaluate the compatibility between GGCa and the two plastic containers. After 3 months of storage at 25 °C, none of the eleven additives were detected in GGCa solutions. The safety concern threshold (SCT) and of the analytical evaluation threshold (AET) were evaluated to discriminate the need to identify and qualify unknown peaks.

Implementation of an interprofessional team-based learning program involving seven undergraduate health and social care programs from two universities, and students' evaluation of their readiness for interprofessional learning.

BACKGROUND: Interprofessional learning is gaining momentum in revolutionizing healthcare education. During the academic year 2015/16, seven undergraduate-entry health and social care programs from two universities in Hong Kong took part in an interprofessional education program. Based on considerations such as the large number of students involved and the need to incorporate adult learning principles, team-based learning was adopted as the pedagogy for the program, which was therefore called the interprofessional team-based learning program (IPTBL). The authors describe the development and implementation of the IPTBL program and evaluate the effectiveness of the program implementation. METHODS: Eight hundred and one students, who are predominantly Chinese, participated in the IPTBL. The quantitative design (a pretest-posttest experimental design) was utilized to examine the students' gains on their readiness to engage in interprofessional education (IPE). RESULTS: Three instructional units (IUs) were implemented, each around a clinical area which could engage students from complementary health and social care disciplines. Each IU followed a team-based learning (TBL) process: pre-class study, individual readiness assurance test, team readiness assurance test, appeal, feedback, and application exercise. An electronic platform was developed and was progressively introduced in the three IUs. The students' self-perceived attainment of the IPE learning outcomes was high. Across all four subscales of RIPLS, there was significant improvement in student's readiness to engage in interprofessional learning after the IPTBL. A number of challenges were identified: significant time involvement of the teachers, difficulty in matching students from different programs, difficulty in making IPTBL count towards a summative assessment score, difficulty in developing the LAMS platform, logistics difficulty in managing paper TBL, and inappropriateness of the venue. CONCLUSIONS: Despite some challenges in developing and implementing the IPTBL program, our experience showed that TBL is a viable pedagogy to be used in interprofessional education involving hundreds of students. The significant improvement in all four subscales of RIPLS showed the effects of the IPTBL program in preparing students for collaborative practice. Factors that contributed to the success of the use of TBL for IPE are discussed.

Managing Cardiovascular Risk of Macrolides: Systematic Review and Meta-Analysis.

INTRODUCTION: It was postulated that antibiotics including macrolides could be used for the secondary prevention of coronary heart disease but recent studies showed that macrolides increase the cardiovascular risk. We aimed to review the evidence of cardiovascular risk associated with macrolides regarding duration of effect and risk factors; and to explore the potential effect of statins for the prevention of cardiovascular events as a result of macrolide use. METHODS: Several electronic databases (PubMed, EMBASE, Cochrane library) were searched to identify eligible studies. Observational studies and randomized controlled trials that investigated the association between macrolides and cardiovascular events in adults aged ≥18 years were included. A meta-analysis was conducted to investigate the short- and long-term risks of cardiovascular mortality, myocardial infarction, arrhythmia, and stroke. Methodological quality was assessed by the Newcastle-Ottawa scale and the Cochrane Collaboration's tool. The body of evidence was evaluated by the Grading of Recommendations Assessment, Development, and Evaluation guidelines. RESULTS: Observational studies were found to have a short-term risk of cardiovascular outcomes including cardiovascular mortality, myocardial infarction, and arrhythmia associated with macrolides but no risk was found in randomized controlled trials. However, no association for long-term risk (ranging from >30 days to >3 years) was observed in observational studies or randomized controlled trials. LIMITATIONS: The included studies reported different units of denominators for absolute risk and used different outcome definitions, which might increase the heterogeneity. CONCLUSIONS: More studies are required to investigate the short-term cardiovascular outcomes associated with different types of macrolides. Future studies are warranted to evaluate the effect of statins for preventing excess acute cardiovascular events associated with clarithromycin or other macrolides.

Herbal tea extracts inhibit Cytochrome P450 3A4 in vitro.

OBJECTIVES: Ciclosporin and sirolimus, two immunosuppressive agents with narrow therapeutic windows, are mainly metabolized by Cytochrome 3A4 (CYP3A4). A clinical case of toxic blood levels of these drugs after the consumption of a '24-flavours' tea was reported. This study aims to identify the causative ingredients of the 24-flavour herbal tea in the inhibition of CYP3A4 metabolism. METHODS: Two commercially available 24-flavour tea products purchased in Hong Kong and the six plant constituents were tested for their CYP3A4 inhibitory effects utilizing an in-vitro fluorometric assay. KEY FINDINGS: Of the commercially available teas available in Hong Kong, the most potent inhibitory effect was observed with the tea consumed in the initial clinical case. Of the six universal constituents, chrysanthemum exhibited the greatest inhibitory effect, with an IC50 of 95.7 µg/ml. Dandelion, liquorice and bishop's weed have IC50 of 140.6, 148.4 and 185.5 µg/ml, respectively. Field mint and Japanese honeysuckle have weaker inhibitory effect on CYP3A4 with IC50 of 1153.3 and 1466.3 µg/ml. CONCLUSIONS: This study confirms the possible implication of herbal tea constituents in the inhibition of ciclosporin and sirolimus' CYP3A4 metabolism. Combined usage of herbal teas with drug should be closely monitored.

Oral transmucosal drug delivery for pediatric use.

The formulation of medicines for children remains a challenge. An ideal pediatric formulation must allow accurate dose administration and be in a dosage form that can be handled by the target age group. It is also important to consider the choices and the amount of excipients used in the formulation for this vulnerable age group. Although oral formulations are generally acceptable to most pediatric patients, they are not suitable for drugs with poor oral bioavailability or when a rapid clinical effect is required. In recent years, oral transmucosal delivery has emerged as an attractive route of administration for pediatric patients. With this route of administration, a drug is absorbed through the oral mucosa, therefore bypassing hepatic first pass metabolism and thus avoiding drug degradation or metabolism in the gastrointestinal tract. The high blood flow and relatively high permeability of the oral mucosa allow a quick onset of action to be achieved. It is a simple and non-invasive route of drug administration. However, there are several barriers that need to be overcome in the development of oral transmucosal products. This article aims to provide a comprehensive review of the current development of oral transmucosal delivery specifically for the pediatric population in order to achieve systemic drug delivery. The anatomical and physiological properties of the oral mucosa of infants and young children are carefully examined. The different dosage forms and formulation strategies that are suitable for young patients are discussed.

Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis.

BACKGROUND: Tofacitinib is a disease-modifying antirheumatic drug (DMARD) which was recently approved by US Food and Drug Administration (FDA). There are several randomised clinical trials (RCTs) that have investigated the efficacy and safety of tofacitinib in adult patients with rheumatoid arthritis (RA). A systematic review with a meta-analysis of RCTs was undertaken to determine the efficacy and safety of tofacitinib in treating patients with RA. METHODS: Electronic and clinical trials register databases were searched for published RCTs of tofacitinib between 2009 and 2013. Outcomes of interest include 20% and 50% improvement in the American College of Rheumatology Scale (ACR20 and ACR50) response rates, rates of infection, the number of immunological/haematological adverse events (AEs), deranged laboratory results (hepatic, renal, haematological tests and lipoprotein level) and the incidence of drug withdrawal. RESULTS: Eight RCTs (n = 3,791) were reviewed. Significantly greater ACR20 response rates were observed in patients receiving tofacitinib 5 and 10 mg bid (twice daily) versus placebo at week 12, with risk ratios (RR) of 2.20 (95% CI 1.58, 3.07) and 2.38 (95% CI 1.81, 3.14) respectively. The effect was maintained at week 24 for 5 mg bid (RR 1.94; 95% CI 1.55, 2.44) and 10 mg bid (RR 2.20; 95% CI 1.76, 2.75). The ACR50 response rate was also significantly higher for patients receiving tofacitinib 5 mg bid (RR 2.91; 95% CI 2.03, 4.16) and 10 mg bid (RR 3.32; 95% CI 2.33, 4.72) compared to placebo at week 12. Patients in the tofacitinib group had significantly lower mean neutrophil counts, higher serum creatinine, higher percentage change of LDL/HDL and a higher risk of ALT/AST > 1 ULN (upper limit of normal) versus placebo. There were no significant differences in AEs and withdrawal due to AEs compared to placebo. CONCLUSION: Tofacitinib is efficacious and well tolerated in patients with MTX-resistant RA up to a period of 24 weeks. However, haematological, liver function tests and lipoproteins should be monitored. Long-term efficacy and pharmacovigilance studies are recommended.

Systematic review and meta-analysis of the efficacy and safety of perampanel in the treatment of partial-onset epilepsy.

INTRODUCTION: Perampanel is a first-in-class antiepileptic drug approved for adjunctive treatment of partial-onset seizure in patients aged 12 years or older. Published randomised controlled trials (RCTs) had small sample sizes, and meta-analyses have included too few studies to draw conclusive results for the assessment of tolerability, efficacy and safety of perampanel. There is a need to conduct a meta-analysis with a larger dataset and an appropriate study design. OBJECTIVE: The aim of this study was to systematically review the efficacy and safety of perampanel in the treatment of partial-onset epilepsy. METHODS: Electronic and clinical trials databases were searched for RCTs of perampanel published up to March 2013. Outcomes of interest were 50 % responder rates, seizure freedom, treatment-emergent adverse events (TEAEs) and incidence of withdrawal. Meta-analysis was performed to investigate the outcomes of interest. RESULTS: Five RCTs with a total of 1,678 subjects were included. The 50 % responder rates were significantly greater in patients receiving 4, 8 and 12 mg perampanel versus placebo, with risk ratios of 1.54 (95 % CI 1.11-2.13), 1.80 (95 % CI 1.38-2.35) and 1.72 (95 % CI 1.17-2.52), respectively. There was no statistical evidence of a difference in seizure freedom between 8 or 12 mg perampanel and placebo. Of the five commonly reported TEAEs included, both dizziness and somnolence were statistically associated with 8 mg perampanel, whilst dizziness was statistically associated with 12 mg perampanel. Incidences of withdrawal due to adverse events were significantly higher in the 8 mg and 12 mg perampanel groups versus placebo. CONCLUSION: The use of perampanel resulted in a statistically significant reduction of seizure frequency with respect to the 50 % responder rate in patients with partial-onset epilepsy. Perampanel is well tolerated at 4 mg and reasonably tolerated at 8 and 12 mg. Further clinical and pharmacovigilance studies are required to investigate the long-term efficacy and safety of perampanel in the management of other types of epilepsy.

Dendritic cell expression of the Notch ligand jagged2 is not essential for Th2 response induction in vivo.

We have addressed the hypothesis that Notch ligands play a decisive role in determining the ability of antigen-presenting cells to influence T cell polarization. Dendritic cells displayed distinct expression profiles of Delta and Jagged ligands for Notch when exposed to biologically relevant pathogen preparations associated with Th1 or Th2 responses. Expression of delta4 was increased, and jagged2 decreased, after dendritic cell exposure to the Th1-promoting bacterium Propionibacterium acnes. In contrast, soluble egg antigen (SEA) from the parasitic helminth Schistosoma mansoni, a potent Th2 inducer, failed to significantly alter dendritic cell expression of any of the Notch ligands measured. Irrespective of this, jagged2-deficient dendritic cells were severely impaired in their ability to instruct Th2 polarization of naive T cells in vitro. However, the ability of SEA-pulsed jagged2-deficient dendritic cells to induce a Th2 response in vivo was unimpaired relative to jagged2-sufficient dendritic cells. Further, jagged2-deficient dendritic cells activated by P. acnes exhibited no evidence of enhanced (or impaired) Th1 induction in vivo. These data suggest that, although involved in Th2 direction in vitro, jagged2 is not fundamentally required for Th2 induction by SEA-activated dendritic cells in vivo.

Dendritic cell expression of OX40 ligand acts as a costimulatory, not polarizing, signal for optimal Th2 priming and memory induction in vivo.

Costimulatory cross-talk can occur at multiple cellular levels to potentiate expansion and polarization of Th responses. Although OX40L ligand (OX40L) is thought to play a key role in Th2 development, the critical cellular source of this molecule has yet to be identified. In this study, we demonstrate that OX40L expression by the initiating dendritic cell (DC) is a fundamental requirement for optimal induction of primary and memory Th2 responses in vivo. Analysis of the kinetics of the residual Th2 response primed by OX40L-deficient DC suggested a failure to stimulate appropriate expansion and/or survival of T cells, rather than an inability to polarize per se. The dependence upon OX40L was predominantly due to the provision of signaling through OX40 rather than retrograde signaling to the DC. Mechanistically, impaired Th2 priming in the absence of OX40L was not due to exaggerated regulation because there was no evidence of increased expansion or function of regulatory cell populations, suppression through IL-10 production, or hyporesponsiveness to secondary challenge. These data define a critical role for DC-derived OX40L in the induction and development of Th2 responses in vivo.

A novel promoter for the 11beta-hydroxysteroid dehydrogenase type 1 gene is active in lung and is C/EBPalpha independent.

11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) increases intracellular glucocorticoid action by converting inactive to active glucocorticoids (cortisol, corticosterone) within cells. It is highly expressed in glucocorticoid target tissues including liver and lung, and at modest levels in adipose tissue and brain. A selective increase in adipose 11beta-HSD1 expression occurs in obese humans and rodents and is likely to be of pathogenic importance in the metabolic syndrome. Here we have used 5' rapid amplificaiton of cDNA ends (RACE) to identify a novel promoter, P1, of the gene encoding 11beta-HSD1. P1 is located 23 kb 5' to the previously described promoter, P2. Both promoters are active in liver, lung, adipose tissue, and brain. However, P1 (encoding exon 1A) predominates in lung and P2 (encoding exon 1B) predominates in liver, adipose tissue, and brain. Adipose tissue of obese leptin-deficient C57BL/6J-Lepob mice showed higher expression only of the P2-associated exon 1B-containing 11beta-HSD1 mRNA variant. In contrast to P2, which is CAAAT/enhancer binding protein (C/EBP)-alpha inducible in transiently transfected cells, the P1 promoter was unaffected by C/EBPalpha in transfected cells. Consistent with these findings, mice lacking C/EBPalpha had normal 11beta-HSD1 mRNA levels in lung but showed a dramatic reduction in levels of 11beta-HSD1 mRNA in liver and brown adipose tissue. These results therefore demonstrate tissue-specific differential regulation of 11beta-HSD1 mRNA through alternate promoter usage and suggest that increased adipose 11beta-HSD1 expression in obesity is due to a selective increase in activity of the C/EBPalpha-regulated P2 promoter.