Drug-Drug Interactions and Actual Harm to Hospitalized Patients: A Multicentre Study Examining the Prevalence Pre- and Post-Electronic Medication System Implementation.

INTRODUCTION: Drug-drug interactions (DDIs) have potential to cause patient harm, including lowering therapeutic efficacy. This study aimed to (i) determine the prevalence of potential DDIs (pDDIs); clinically relevant DDIs (cDDIs), that is, DDIs that could lead to patient harm, taking into account a patient's individual clinical profile, drug effects and severity of potential harmful outcome; and subsequent actual harm among hospitalized patients and (ii) examine the impact of transitioning from paper-based medication charts to electronic medication management (eMM) on DDIs and patient harms. METHODS: This was a secondary analysis of the control arm of a controlled pre-post study. Patients were randomly selected from three Australian hospitals. Retrospective chart review was conducted before and after the implementation of an eMM system, without accompanying clinical decision support alerts for DDIs. Harm was assessed by an expert panel. RESULTS: Of 1186 patient admissions, 70.1% (n = 831) experienced a pDDI, 42.6% (n = 505) a cDDI and 0.9% (n = 11) an actual harm in hospital. Of 15,860 pDDIs identified, 27.0% (n = 4285) were classified as cDDIs. The median number of pDDIs and cDDIs per 10 drugs were 6 [interquartile range (IQR) 2-13] and 0 (IQR 0-2), respectively. In cases where a cDDI was identified, both drugs were 44% less likely to be co-administered following eMM (adjusted odds ratio 0.56, 95% confidence interval 0.46-0.73). CONCLUSION: Although most patients experienced a pDDI during their hospital stay, less than one-third of pDDIs were clinically relevant. The low prevalence of harm identified raises questions about the value of incorporating DDI decision support into systems given the potential negative impacts of DDI alerts.

Clinical report: one year of treatment of Proteus syndrome with miransertib (ARQ 092).

A 20-yr-old man with Proteus syndrome (PS) and somatic mosaicism of the AKT1 c.49G > A p.(E17K) variant had asymmetric overgrowth of the right frontal and facial bones, asymmetric spinal overgrowth with thoracolumbar scoliosis, dilatation of the inferior vena cava, testicular cystadenoma, bilateral knee deformities, macrodactyly, and apparent intellectual disability. Miransertib (ARQ 092) is an oral, allosteric, selective pan-AKT inhibitor initially developed for cancer therapeutics, now being evaluated for the treatment of PS. After baseline evaluation, the patient started unblinded treatment of 10 mg oral miransertib daily (∼5 mg/m2/day), escalated to 30 mg daily (∼15 mg/m2/day), and then to 50 mg daily (∼25 mg/m2/day) after 3 mo of treatment. Adverse events included dry mouth, one episode of gingivostomatitis, and loose, painful dentition due to preexisting periodontal disease, all of which resolved spontaneously. After 11 mo of treatment, the patient reported improved general well-being, increased mobility of the ankle, spine, and hands, a subjective decrease in size of the right facial bone overgrowth, and reduced areas of cerebriform connective tissue nevi on the soles. Whole-body MRI findings were stable without apparent disease progression. We conclude that 1 yr of treatment with miransertib was beneficial in this case.

Optimising computerised decision support to transform medication safety and reduce prescriber burden: study protocol for a mixed-methods evaluation of drug-drug interaction alerts.

INTRODUCTION: Drug-drug interaction (DDI) alerts in hospital electronic medication management (EMM) systems are generated at the point of prescribing to warn doctors about potential interactions in their patients' medication orders. This project aims to determine the impact of DDI alerts on DDI rates and on patient harm in the inpatient setting. It also aims to identify barriers and facilitators to optimal use of alerts, quantify the alert burden posed to prescribers with implementation of DDI alerts and to develop algorithms to improve the specificity of DDI alerting systems. METHODS AND ANALYSIS: A controlled pre-post design will be used. Study sites include six major referral hospitals in two Australian states, New South Wales and Queensland. Three hospitals will act as control sites and will implement an EMM system without DDI alerts, and three as intervention sites with DDI alerts. The medical records of 280 patients admitted in the 6 months prior to and 6 months following implementation of the EMM system at each site (total 3360 patients) will be retrospectively reviewed by study pharmacists to identify potential DDIs, clinically relevant DDIs and associated patient harm. To identify barriers and facilitators to optimal use of alerts, 10-15 doctors working at each intervention hospital will take part in observations and interviews. Non-identifiable DDI alert data will be extracted from EMM systems 6-12 months after system implementation in order to quantify alert burden on prescribers. Finally, data collected from chart review and EMM systems will be linked with clinically relevant DDIs to inform the development of algorithms to trigger only clinically relevant DDI alerts in EMM systems. ETHICS AND DISSEMINATION: This research was approved by the Hunter New England Human Research Ethics Committee (18/02/21/4.07). Study results will be published in peer-reviewed journals and presented at local and international conferences and workshops.

Active promotion of antibiotic guidelines: an intensive program.

John Hunter Hospital, a 600 bed tertiary referral centre, has an antimicrobial working party comprising representatives from pharmacy, microbiology and infectious diseases areas, which is responsible for the development, implementation and evaluation of guidelines for the appropriate use of antimicrobials. Activities include the development and promotion of a restricted antimicrobial policy, and specific guidelines for the management of pneumonia, and surgical prophylaxis and wound infection. These guidelines are available on the hospital intranet, in hard copies in all wards, and on laminated cards (10 x 6.5 cm) attached to the hospital identification tag. Active promotion of the guidelines is undertaken at orientation and via a 2 week intensive period four times per year (corresponding with the registrar rotation), weekly meetings and follow up of non-compliance courses directly with the attending medical officer. Education and feedback to specific groups is provided as required. Other projects include a campaign to encourage oral antibiotics where indicated. Regular drug utilisation evaluations are undertaken to measure outcomes, along with other indicators of antibiotic use such as the prevalence of antimicrobial resistance. Appropriate prescribing of third generation cephalosporins has increased from 21 per cent to 52 per cent (p = 0.008) of courses between December 1999 and June 2001.