Development and application of Adverse drug reactions reports QUality Algorithm (AQUA-12) score: a single-centre quality improvement initiative.

PURPOSE: To develop a reliable assessment tool to monitor the quality of adverse drug reaction (ADR) reports and evaluate its performance within a quaternary hospital setting. METHODS: Adverse drug reactions report QUality Algorithm (AQUA-12) was developed by a multidisciplinary team with the expertise in the management of ADRs. The design was based on data elements required to establish medication causality. Inter-rater reliability of AQUA-12 was evaluated over three rounds in two phases: development and prospective evaluation phases, by independent assessors both internal and external to the institutional ADR review processes. The characteristics and quality of ADR reports were subsequently assessed, and potential factors contributing to low-quality reports were identified. RESULTS: A total of 70 ADR reports were assessed, 20 in development and 50 in evaluation phases. The inter-rater reliability of AQUA-12 was found to be excellent in all three rounds (Cronbach's alpha of  ≥ 0.9, p < 0.001 for all). Approximately one in five reports concerned immediate hypersensitivity reactions while delayed hypersensitivity reactions constituted 60% of all reactions. AQUA-12 identified 18 (25.7%) reports as 'low-quality' with a score of  < 10. Identification of suspected medications (37.1%), description of index ADR (27.1%), and key events (ADR narrative, 35.7%) were the top data elements incomplete or missing from all reports. Univariable analyses identified the severity of the reaction as a factor associated with low quality of reports (p = 0.008). CONCLUSIONS: AQUA-12 is a practical and highly reliable assessment tool that can be utilised in hospital settings to regularly monitor the completeness of ADR reports to guide quality improvement initiatives.

Safety of Intravenous Iron Following Infusion Reactions.

BACKGROUND: Where an ongoing requirement for intravenous iron replacement exists after an index infusion reaction, current recommendations are limited to expert opinion and isolated case reports. OBJECTIVE: To evaluate the safety of recommencing an infusion or subsequent rechallenge following an infusion reaction to intravenous iron. METHODS: Infusion reactions to intravenous iron occurring between January 1, 2010, and December 31, 2019, at a metropolitan health network were identified. Patient characteristics, reaction type (mild, moderate, or severe hypersensitivity, delayed, or Fishbane: transient flushing and truncal myalgias), and outcomes of recommencing the index infusion or subsequent rechallenge were examined. RESULTS: Among 13,509 iron infusions, 195 infusion reactions occurred in 195 patients (1.4% of infusions). Recommencement of the index infusion (generally with a reduced infusion rate and premedication) was tolerated in 33 of 33 patients with Fishbane (20 of 20) or mild (9 of 9) and moderate (4 of 4) hypersensitivity reactions. Subsequent rechallenge (generally at standard infusion rates to an alternative formulation, ferric carboxymaltose) was successful in 68 of 69 patients with Fishbane (23 of 23), mild (26 of 26), moderate (16 of 17), and severe (3 of 3) hypersensitivity, or delayed (2 of 2) reactions. All 9 patients rechallenged to the original formulation (iron polymaltose) completed the infusion. CONCLUSIONS: Following an infusion reaction to intravenous iron infusion, recommencement of the index infusion is safe for Fishbane or mild and moderate hypersensitivity reactions. Subsequent rechallenge to an alternative formulation is tolerated, including in severe hypersensitivity reactions (albeit based on limited numbers). Where alternative formulations are not available, rechallenge to the same formulation could be considered, depending on the risk-benefit profile.

Implementing a sustainable medication reconciliation process in Australian hospitals: The World Health Organization High 5s project.

BACKGROUND: Medication reconciliation (medrec) is a mandated patient safety strategy by national, including Australian, accreditation bodies. Yet there are no validated performance measures. OBJECTIVE: To determine the feasibility of implementing the World Health Organization (WHO) Medrec Standard Operating Protocol (SOP) in a range of Australian acute care facilities to achieve measurable and sustainable reductions in medication discrepancies occurring at admission. METHODS: A multicentre, prospective national study was conducted in ten academic, urban and regional hospitals to implement the SOP using WHO High 5s project and quality improvement methodology. Sites collected data on the rate of medrec performed within 24 h of admission in a random selection of 50 patients aged ≥65 years admitted via the emergency department, monthly for four years. Medrec quality was reviewed in a subset of 30 patients using three performance measures. Barriers, enablers and benefits of SOP implementation were collected using qualitative surveys. RESULTS: Ten health services reviewed 42,003 patient records. Of these, 20,162 (49.5%) had medicines reconciled within 24 h of admission. Four services increased, two decreased, and in four, medrec completion rates remained static. Mean number of unintentional and undocumented intentional medication discrepancies per patient decreased: 0.21 to 0.16 (p = 0.001) and 0.34 to 0.08 (p = 0.003), respectively. Unintentional discrepancies decreased from 15.2% to 11.1% (p = 0.001). Barriers to full implementation included: medrec not seen as a priority, limited resources and lack of electronic systems integration. Enablers included: use of medrec measures for feedback, educational resources, and 7-day week clinical pharmacy services. Benefits included improvements in medication safety culture and multidisciplinary teamwork. CONCLUSIONS: The WHO SOP was feasible, although challenging, to implement in a range of acute health services, and produced measureable and sustainable improvements in medicines information accuracy on admission. Sustaining the quantum of quality and timely medrec requires investment in pharmacist resources and electronic systems integration.

Medication-related anaphylaxis treated in hospital: Agents implicated, patient outcomes, and management lessons.

PURPOSE: On background of increasing medication-related anaphylaxis rates in Australia, our aim was to determine epidemiology, outcomes, adverse drug reaction (ADR) reporting rates, and accuracy of coding in patients treated for nonantimicrobial medication-related anaphylaxis in our hospital network. METHODS: From January 2010 to December 2015 patients treated in our hospital network for medication-related anaphylaxis were identified using International Classification of Diseases, 10th Edition diagnosis code T88.6. Cases were also extracted from the hospital ADR database. Medical records were reviewed to ensure consistent diagnosis and to extract clinical, documentation, and outcome data. RESULTS: Of 1110 patients coded as T88.6, 177 (15.9%) met the medication-related anaphylaxis definition. Eighty (40.8%) had anaphylaxis due to nonantimicrobial agents. Thirteen of these (16.3%) had a previous reaction to the same medication/group. In 51 (63.8%) patients, anaphylaxis occurred during inpatient stay, with 31 reactions occurring during surgery. Eighty-five medications were implicated, most commonly neuromuscular blocking agents (31, 36.5%) and nonsteroidal anti-inflammatory drugs. No trends were noted over the 6-year period, and there was no anaphylaxis-related mortality. Fifty-three (66.3%) patients were assessed in allergy clinics. One in 10 cases did not have the reaction documented in the discharge summary. Adverse drug reaction reports were received for 38 patients (47.5%). CONCLUSIONS: Although acute patient outcomes were excellent, gaps in practice were noted regarding ADR coding accuracy and reporting rates. One in 6 patients had a prior hypersensitivity reaction to a similar medication, so we recommend accurate documentation, ADR review with allergy follow-up, and patient held information to decrease re-exposure risk.

Drug-induced liver injury is frequently associated with severe cutaneous adverse drug reactions: experience from two Australian tertiary hospitals.

BACKGROUND: Drug-induced liver injury (DILI) can be associated with certain cutaneous adverse drug reaction (cADR). AIMS: To demonstrate the prevalence of DILI in patients with cADRs. Severity and patterns of liver injury, risk factors, causal medications and outcomes are also examined. METHODS: A retrospective cohort study of patients with cADRs was conducted across two hospitals in Australia. Patients were identified through cross-linkage of multiple databases. RESULTS: One hundred and four patients with cADRs were identified. Of these, 33 (31.7%) had liver injury, representing 50% of patients with drug reaction with eosinophilia and systemic symptoms, and 30.2% of patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Most cases of liver injury (69.7%) were of a cholestatic/mixed pattern with severe disease in 18.2%. No significant risk factors for development of liver injury were noted, but peripheral lymphocytosis may represent a risk in patients with SJS (odds ratio, OR = 6.0, 95% confidence interval, CI: 1.8-19.7, P = 0.003). Antimicrobials were the most common class to be implicated in DILI. The median length of inpatient stay was longer in patients with liver injury compared to those without (19 vs 11 days, P = 0.002). The mortality rate in those with liver injury was 15.2% and 9.9% in those without. No patients required liver transplantation. CONCLUSIONS: DILI commonly occurs in patients with cADRs and is associated with longer inpatient stay. Patients with SJS/TEN and peripheral lymphocytosis appear to be at higher risk for developing associated liver injury.

Old but not forgotten: Antibiotic allergies in General Medicine (the AGM Study).

OBJECTIVES: To determine the nature, prevalence and description accuracy of recorded antibiotic allergy labels (AALs) in a cohort of general medical inpatients, and to assess the feasibility of an oral antibiotic re-challenge study. DESIGN: Multicentre cross-sectional study. SETTING AND PARTICIPANTS: All patients admitted to the general medical units of Austin Health and Alfred Health, 18 May - 5 June 2015. MAIN OUTCOME MEASURES: Baseline demographics, medical and allergy history, infection diagnoses and antibiotic prescribing data for general medical inpatients were collected. A questionnaire was administered to clarify AAL history, followed by correlation of responses with electronic and admissions record descriptions. A hypothetical oral re-challenge in a supervised setting was offered to patients with low risk allergy phenotypes (non-immediate reaction, non-severe cutaneous adverse reaction, or unknown reaction more than 10 years ago). RESULTS: Of the 453 inpatients, 107 (24%) had an AAL (median age, 82 years; interquartile range, 74-87 years); 160 individual AALs were recorded, and there was a mismatch in AAL description between recording platforms in 25% of cases. Most patients with an AAL were women (64%; P < 0.001), and more presented with concurrent immunosuppression than those without an AAL (23% v 8%; P < 0.001). ß-Lactam penicillins were employed less frequently in patients with an AAL (16% v 35%; P = 0.02), while ceftriaxone (32% v 20%; P = 0.02) and fluoroquinolones (6% v 2%; P = 0.04) were used more often. Fifty-four per cent of patients with AALs were willing to undergo oral re-challenge, of whom 48% had a low risk allergy phenotype. CONCLUSIONS: AAL prevalence in general medical inpatients was 24%, and was associated with excessive use of broad spectrum antibiotics. Allergies in a large proportion of patients with AALs were incorrectly documented, and were non-immune-mediated and potentially amenable to oral re-challenge. A direct oral re-challenge study in carefully selected patients with low risk allergy phenotypes appears feasible.

Recommendations and Low-Technology Safety Solutions Following Neuromuscular Blocking Agent Incidents.

BACKGROUND: Neuromuscular blocking agents (NMBs) are high-risk medications used to facilitate endotracheal intubation and artificial ventilation. In an incident at a metropolitan tertiary referral and teaching public hospital in Australia, a neurosurgical patient became unresponsive at the start of surgery. It was determined that cisatracurium was administered in error in place of midazolam; the patient was ventilated and the emergency surgery continued. Two additional non-operating room (OR) drug-swap cases involving cisatracurium were reported within 12 months of this event, resulting in a comprehensive review of NMB safety. METHODS: A root cause analysis (RCA) resulted in multiple interventions to decrease the risk of selection and administration errors: (1) review of NMB packaging and introduction of in-house NMB labeling by pharmacy procurement staff before distribution; (2) implementation of a medication administration in anesthetics guideline with ongoing education; (3) audit of storage with removal of NMBs; (4) review of new products by medication safety pharmacists and a senior anesthetist before distribution; and (5) use of red-barrel syringes for administering NMBs was expanded to all areas using NMBs to minimize syringe-swap incidents. RESULTS: In the four years since full implementation of interventions, there have been no reports of cisatracurum selection errors. An incident of atracurium administration resulted in further recommendations for review of OR cart storage. Ongoing monitoring via medication safety walkrounds, by OR staff, by the perioperative pharmacist, and through the hospital's medication incident monitoring system has not detected any further NMB incidents. CONCLUSIONS: Technological solutions have been shown to decrease the risk of NMB errors, yet multifaceted low-technology solutions may be an effective, cheaper alternative.

Medication Safety: Experiential Learning for Pharmacy Students and Staff in a Hospital Setting.

Medication Safety has been an established pharmacy specialty in Australian hospitals since the early 2000s and is now one of the ten Australian hospital accreditation standards. Although advances have occurred, medication-related patient harm has not been eradicated. Victorian undergraduate pharmacy programs include some aspects of medication safety, however clinical pharmacy experience, along with interpersonal and project management skills, are required to prepare pharmacists to be confident medication safety practitioners. This article outlines the range of medication safety-related training offered at an Australian tertiary teaching hospital, including; on-site tutorial for undergraduate students, experiential placement for pharmacy interns, orientation for pharmacy staff and resources for credentialing pharmacists for extended roles. Improvements continue to be made, such as electronic medication management systems, which increase the safe use of medications and facilitate patient care. Implementation and evaluation of these systems require medication safety expertise. Patients' engaging in their own care is an acknowledged safety improvement strategy and is enhanced by pharmacist facilitation. Building educator skills and integrating experiential teaching with university curricula should ensure pharmacists have both the knowledge and experience early in their careers, in order to have a leading role in future medication management.

Probable fenofibrate-induced acute generalized exanthematous pustulosis.

PURPOSE: The case of a patient who experienced a severe adverse reaction requiring emergency treatment after a single dose of fenofibrate is described. SUMMARY: A 58-year-old woman with type 1 diabetes was hospitalized for treatment of an extensive blistering rash on the buttocks and trunk accompanied by fever, hypotension, tachycardia, neutrophilia, impaired renal function, and liver enzyme abnormalities. She reported that two days previously she had developed fever and vomiting four hours after taking her first dose of fenofibrate (145 mg). The patient required vasopressor support and was initially treated with broad-spectrum antibiotics for 3 days and a course of immune globulin. On hospital day 4, histopathology returned results consistent with acute generalized exanthematous pustulosis (AGEP), and the patient was subsequently treated with topical steroids. Gradual resolution of AGEP was noted at the time of her discharge from the hospital on day 7 and at one-week follow-up. Analysis of the case using the adverse drug reaction probability scale of Naranjo et al. yielded a score of 5, indicating a probable association between fenofibrate use and AGEP development. AGEP is a predominantly drug-induced condition but is not typically associated with fenofibrate use. Cutaneous eruptions in AGEP are often accompanied by systemic symptoms (e.g., fever, leukocytosis), and the disorder can also be associated with impaired creatinine clearance and elevated aminotransaminase levels. CONCLUSION: A woman with type 1 diabetes developed AGEP after taking a single dose of fenofibrate. Her cutaneous symptoms began to resolve within days of discontinuation of fenofibrate use.

Multicentre study to develop a medication safety package for decreasing inpatient harm from omission of time-critical medications.

QUALITY ISSUE: Omitting time-critical medications leads to delays in treatment and may result in patient harm. INITIAL ASSESSMENT: Published studies show that omission of prescribed medication doses is common. Although most are inconsequential, up to 86% of omitted medications place patients at some risk of harm. SOLUTION: Funding was obtained to develop a medication safety package to facilitate decreasing omitted dose incidents by audit, education and feedback. IMPLEMENTATION: A panel of nursing and pharmacy hospital staff in Victoria, Australia, reviewed existing audit tools and published studies to develop a critical medication list and audit tool. The tool, definitions and instructions were tested in 11 rural, urban and teaching hospitals. Qualitative feedback was sought to refine the tool using a Plan-Do-Study-Act model. An educational presentation was developed using reported incidents. EVALUATION: Staff in 11 hospitals tested the audit tool in 321 patients receiving 17 361 doses of medication. Feedback indicated audit data were useful for informing improvements in practice and for accreditation. The educational material consists of the User Guide, plus a presentation for nursing staff illustrated by six cases with questions, with instructions on how to decrease harm from omitted doses by ensuring correct documentation and prioritising time-critical medications. LESSONS LEARNED: A medication safety package using standard definitions and a critical medication list was successfully tested. It is now used by nursing and pharmacy staff across the state. Several interstate hospitals are using the tools as part of their hospital medication safety programmes.

Changes in anticonvulsant prescribing for Australian children: implications for Quality Use of Medicines.

AIMS: The evidence-base guiding choices between newer versus established anticonvulsants in children is limited. Inappropriate use exposes children to potentially ineffective and/or harmful medicines. Our objective is to describe recent anticonvulsant prescribing patterns in the Australian paediatric population, evaluating overall trends and extent of off-label prescribing of newer agents. METHODS: Aggregated national data on 15 anticonvulsants with Pharmaceutical Benefits Scheme subsidy dispensed by community pharmacies for children aged <16 years were obtained from the Drug Utilisation Subcommittee, which is part of the Australian Government Department of Health and Ageing. We analysed trends for the five most prescribed anticonvulsants dispensed between 2002 and 2009 and off-label prescribing for agents where approved Australian product information stipulates a minimum age. RESULTS: Valproate was the most frequently prescribed anticonvulsant with no marked change in prescription numbers per 1000 children aged 0-16 years (11.3-11.8 prescriptions/year). Lamotrigine was the most frequently prescribed newer anticonvulsant (7.9-9.3 prescriptions/year). Carbamazepine prescriptions decreased by 38% and topiramate prescriptions increased by 19% over the 7-year study period; 3.6% of topiramate prescriptions were off-label (by age) for children aged <2 years. Since Pharmaceutical Benefits Scheme listing in 2003, levetiracetam prescriptions increased steeply to 2.5 prescriptions/year per 1000 children in 2009; 4.2% were off-label for children aged <4 years. CONCLUSIONS: The substantial reduction in carbamazepine use and corresponding increase in newer anticonvulsant prescribing, including off-label uses, raises questions about potentially suboptimal Quality Use of Medicines. Such major changes in prescribing may have important clinical and economic consequences. Further study to better understand paediatric prescribing choices and outcomes is needed.

Pertussis prevention and treatment: a call for wider access to azithromycin.

Azithromycin is recommended as the first-line antibiotic for the prophylaxis and treatment of pertussis, a common vaccine-preventable communicable disease. Azithromycin is better tolerated than other macrolide antibiotics. Access to azithromycin is limited, as the product information and the Pharmaceutical Benefits Scheme do not include azithromycin for pertussis. Issues regarding access to azithromycin are highlighted in a case report of pertussis exposure in a tertiary paediatric hospital.

Off-label use of medicines: consensus recommendations for evaluating appropriateness.

Off-label prescribing is the prescription of a registered medicine for a use that is not included in the product information. The practice is common, with rates up to 40% in adults and up to 90% in paediatric patients. Off-label prescribing is not illegal and may sometimes be clinically appropriate, but is associated with a number of clinical, safety and ethical issues. To date, no explicit guidance has been available to help clinicians assess appropriateness in off-label prescribing. We describe the development of a guide for clinicians, policymakers and funders of health care in evaluating the appropriateness of medicines proposed for off-label use. Three broad categories of appropriate off-label use are identified:off-label use justified by high-quality evidence; use within the context of a formal research proposal; and exceptional use, justified by individual clinical circumstances. An appropriate process for informed consent is proposed for each category. If there is no high-quality evidence supporting off-label use, and the medicine is not suitable for exceptional or research indications, its use is generally not recommended. This will reduce inappropriate use, enhance patient safety by reducing exposure to unnecessary risk, and may stimulate more clinically relevant medicines research.

Pethidine in emergency departments: promoting evidence-based prescribing.

OBJECTIVE: To reduce pethidine prescribing in hospital emergency departments (EDs). DESIGN: Multi-centre drug use evaluation (DUE) process. SETTING AND PARTICIPANTS: Emergency departments in 23 public hospitals (22 in New South Wales, 1 in Victoria) from 1 September 2002 to 31 August 2003. Participating hospitals included seven principal referral hospitals, six major non-teaching hospitals and 10 district or community hospitals. Data for comparison were collected from 12 non-participating hospitals. INTERVENTIONS: Hospital coordinators at each participating hospital were provided with support to implement a range of prescribing interventions in their ED in each of three DUE cycles. Interventions included educational materials (guidelines, posters, prescribing reminders), audit and feedback, and small-group discussions. Three audits of pethidine prescribing were undertaken. Prescribing was compared with evidence-based guidelines and non-concordance identified. MAIN OUTCOME MEASURES: Number of dosage units of parenteral analgesics issued to the ED from each hospital's pharmacy department was recorded monthly and aggregated in 3-month periods. RESULTS: In the 12 months between the preintervention period and the equivalent post-intervention period, pethidine use decreased by 62% in project hospitals (4669 to 1793 units) and 56% in control hospitals (1476 to 648 units). Six months after project completion there was a significantly greater reduction from baseline in participating hospitals (71%; 4669 to 1348 units) compared with non-participating hospitals (64%; 1476 to 532 units; P < 0.001). There was a concurrent increase in use of both morphine and tramadol. CONCLUSION: There was a sustained reduction in pethidine use during the study period, which may indicate successful promotion of safer analgesic prescribing. It is not clear whether changes were a result of collaborative DUE methods or other factors.