Adverse drug reaction causality assessment tools for drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: room for improvement The correct name of the 9th Author is David J. Margolis. The original article was corrected.

Letter to the Editor: Clinically relevant drug–drug interactions among elderly people with dementia

Letter to editor: Clinically relevant drug–drug interactions among elderly people with dementia

Interaction between paracetamol and lamotrigine: new insights from the FDA Adverse Event Reporting System (FAERS) database

Proton pump inhibitors: why this gap between guidelines and prescribing practices in geriatrics?

Medication errors in hospitals in the Middle East: a systematic review of prevalence, nature, severity and contributory factors Abstract Purpose The aim was to critically appraise, synthesise and present the evidence of medication errors amongst hospitalised patients in Middle Eastern countries, specifically prevalence, nature, severity and contributory factors. Methods CINAHL, Embase, Medline, Pubmed and Science Direct were searched for studies published in English from 2000 to March 2018, with no exclusions. Study selection, quality assessment (using adapted STROBE checklists) and data extraction were conducted independently by two reviewers. A narrative approach to data synthesis was adopted; data related to error causation were synthesised according to Reason’s Accident Causation model. Results Searching yielded 452 articles, which were reduced to 50 following removal of duplicates and screening of titles, abstracts and full-papers. Studies were largely from Iran, Saudi Arabia, Egypt and Jordan. Thirty-two studies quantified errors; definitions of ‘medication error’ were inconsistent as were approaches to data collection, severity assessment, outcome measures and analysis. Of 13 studies reporting medication errors per ‘total number of medication orders’/ ‘number of prescriptions’, the median across all studies was 10% (IQR 2–35). Twenty-four studies reported contributory factors leading to errors. Synthesis according to Reason’s model identified the most common being active failures, largely slips (10 studies); lapses (9) and mistakes (12); error-provoking conditions, particularly lack of knowledge (13) and insufficient staffing levels (13) and latent conditions, commonly heavy workload (9). Conclusion There is a need to improve the quality and reporting of studies from Middle Eastern countries. A standardised approach to quantifying medication errors’ prevalence, severity, outcomes and contributory factors is warranted.

Tailored P2Y 12 inhibitor treatment in patients undergoing non-urgent PCI—the POPular Risk Score study Abstract Purpose The POPular Risk Score was developed for the selective intensification of P2Y12 inhibitor treatment with prasugrel instead of clopidogrel in patients undergoing non-urgent percutaneous coronary intervention (PCI) with stent implantation. This score is based on platelet reactivity (VerifyNow P2Y12 assay), CYP2C19 genotyping, and clinical risk factors. Our aim was to determine if the use of this score in clinical practice is associated with a reduction in thrombotic events without increasing bleeding events. Methods In a single-center prospective cohort study, patients with a high risk score were treated with prasugrel and patients with a low risk score with clopidogrel. The risk score–guided cohort was compared with a historic cohort of clopidogrel-treated patients. The endpoint consisted of all-cause death, myocardial infarction, stroke, or stent thrombosis during 1 year of follow-up. TIMI major and minor bleeding events were also analyzed. Results The guided cohort contained 1127 patients, 26.9% of whom were switched to prasugrel according to the POPular Risk Score. The historic cohort contained 893 patients. The incidence of the combined thrombotic endpoint was significantly lower in the guided cohort as compared with the historic cohort (8.4% versus 3.7%, p < 0.001). This strategy was safe with respect to bleeding (4.0% versus 1.3%, p < 0.001, for TIMI major or minor bleeding). Results were comparable after multivariate and propensity score matched and weighted analysis. Conclusion Selective intensification of P2Y12 inhibitor treatment after non-urgent PCI based on the POPular Risk Score is associated with a reduction in thrombotic events without an increase in bleeding events.

Vancomycin population pharmacokinetics for adult patients with sepsis or septic shock: are current dosing regimens sufficient? Abstract Purpose Vancomycin is commonly used for the management of severe infections; however, vancomycin dosing may be challenging in critically ill patients. This observational study aims to describe the population pharmacokinetics of vancomycin in adult patients with sepsis or septic shock. Methods A single-centre retrospective review of adult patients with sepsis or septic shock receiving vancomycin with therapeutic drug monitoring was undertaken. Blood samples taken 1 h after the vancomycin infusion cessation and 30 min prior to the next dose were assayed using the Vitros Crea Slide method. Vancomycin concentrations determined on different days were included. A pharmacokinetic model was developed using Pmetrics for R. Monte Carlo dosing simulations were performed using the final model. Results Vancomycin concentrations were available for 27 adult patients admitted to the intensive care unit with sepsis or septic shock. A one-compartment pharmacokinetic model with inter-occasion variability of clearance and volume of distribution before and after 72 h adequately described the data. Creatinine clearance normalized to body surface area was included as a covariate on vancomycin clearance. The clearance and volume of distribution within 72 h of admission were 7.29 L/h and 54.20 L, respectively. Monte Carlo simulations suggested that for patients with a creatinine clearance of ≥ 80 mL/min/1.73 m2, vancomycin doses of ≥ 2 g every 8 h are required to consistently achieve key therapeutic targets. Conclusions Vancomycin doses ≥ 2 g every 8 h in adult patients with sepsis or septic shock with a creatinine clearance ≥ 80 mL/min/1.73 m2 are likely needed to achieve an optimal therapeutic exposure.

Association between adherence to antihypertensive medications and health outcomes in middle and older aged community dwelling adults; results from the Irish longitudinal study on ageing Abstract Purpose To examine the association between antihypertensive medication (AHTM) implementation adherence and healthcare utilisation in community-dwelling adults aged ≥ 50 years in Ireland. Methods This was a prospective cohort study. The Irish Longitudinal Study on Ageing (TILDA) was linked to pharmacy claims data for participants aged ≥ 50 years. Participants were included if they had ≥ 3 pharmacy claims for one or more AHTM (ATC codes ‘C02’, ‘C03’, ‘C07’, ‘C08’ or ‘C09’) within the year preceding the year of self-reported healthcare utilisation outcome occurrence. Outcomes included self-reported general practitioner (GP), emergency department (ED), outpatient department visits and hospital admissions. Implementation adherence was measured using proportion of days covered (PDC), with participants classified as adherent if the average PDC ≥ 0.8. Negative binomial models were used to analyse the association between AHTM adherence and number of GP, ED, outpatient visits and hospitalisations (adjusted IRR and 95% CI are presented). Results One thousand four hundred thirty-one participants were included. The majority of participants (72.6%) were considered adherent. Good implementation adherence to AHTM was associated with a significant decrease in self-reported GP visits (adjusted IRR 0.91, 95% CI 0.83–0.99). Adherence had no significant impact on the number of ED visits, outpatient visits or hospitalisations reported by TILDA participants. Conclusions Good adherence to AHTM was associated with less self-reported GP visits in this population, suggesting improved overall health status. However, the impact of medication non-adherence on the other self-reported healthcare utilisation outcomes (ED, outpatient visits and hospitalisations) was not evident in this study.

Identification of the caffeine to trimethyluric acid ratio as a dietary biomarker to characterise variability in cytochrome P450 3A activity Abstract Purpose Cytochrome P450 (CYP) 3A plays an important role in the metabolism of many clinically used drugs and exhibits substantial between-subject variability (BSV) in activity. Current methods to assess variability in CYP3A activity have limitations and there remains a need for a minimally invasive clinically translatable strategy to define CYP3A activity. The purpose of this study was to evaluate the potential for a caffeine metabolic ratio to describe variability in CYP3A activity. Methods The metabolic ratio 1,3,7-trimethyluric acid (TMU) to caffeine was evaluated as a biomarker to describe variability in CYP3A activity in a cohort (n = 28) of healthy 21 to 35-year-old males. Midazolam, caffeine, and TMU concentrations were assessed at baseline and following dosing of rifampicin (300 mg daily) for 7 days. Results At baseline, correlation coefficients for the relationship between apparent oral midazolam clearance (CL/F) with caffeine/TMU ratio measured at 3, 4, and 6 h post dose were 0.82, 0.79, and 0.65, respectively. The strength of correlations was retained post rifampicin dosing; 0.72, 0.87, and 0.82 for the ratios at 3, 4, and 6 h, respectively. Weaker correlations were observed between the change in midazolam CL/F and change in caffeine/TMU ratio post/pre-rifampicin dosing. Conclusion BSV in CYP3A activity was well described by caffeine/TMU ratios pre- and post-induction. The caffeine/TMU ratio may be a convenient tool to assess BSV in CYP3A activity, but assessment of caffeine/TMU ratio alone is unlikely to account for all sources of variability in CYP3A activity.