Association Between Nonvitamin K Antagonist Oral Anticoagulants or Warfarin and Liver Injury: A Cohort Study.

INTRODUCTION: The risk of liver injury in patients with atrial fibrillation (AF) using nonvitamin K antagonist oral anticoagulants (NOACs) has not been previously examined using liver function tests as the primary outcome in the real-world setting. This study assessed the association between NOACs (dabigatran, rivaroxaban, and apixaban) and warfarin and the risk of liver injury, as defined by laboratory tests. METHODS: Patients newly diagnosed with AF and prescribed NOACs or warfarin between 2010 and 2016, identified using the Hong Kong Clinical Database and Reporting System, were matched on age, sex, health status scores, comorbidities, and medications by propensity score on a 1:1 ratio. Risk of liver injury, defined as laboratory test values >3 times the upper limit of normal of alanine aminotransferase or aspartate aminotransferase and >2 times the upper limit of normal of total bilirubin, was compared between NOAC and warfarin users using Cox proportional hazards regression. RESULTS: After propensity score matching, 13,698 patients were included, of which 141 (2.1%) NOAC users and 232 (3.4%) warfarin users developed liver injury. The hazard ratio (HR) for NOAC vs warfarin users was 0.71 (95% confidence interval: 0.58-0.89). When comparing individual NOACs, only dabigatran (hazard ratio: 0.63; 95% confidence interval: 0.48-0.82) was associated with a lower risk of liver injury. DISCUSSION: Among patients with AF, NOACs as a group, and dabigatran alone were associated with a significantly lower risk of laboratory-based liver injury when compared with warfarin. However, liver injury occurs more frequently in real-world practice than in NOAC randomized controlled trials.

Pharmacy students' perceptions on environmental sustainability in pharmacy education and practice.

Background: Given the negative environmental impacts of pharmaceuticals, including their contribution to healthcare's carbon footprint, pharmacists have a role in responding to the climate and biodiversity crises. Knowledge and education are required to support transitions to environmentally sustainable pharmacy practice (ESPP). The aim of this study was to explore Australian undergraduate pharmacy students' knowledge and attitudes towards environmental sustainability and ESPP curriculum content. Methods: Participants were surveyed using an anonymous online questionnaire deployed using Qualtrics. The questionnaire comprised of two main sections: the 15-item New Ecological Paradigm (NEP) scale to determine participants' environmental attitude score, and section on students' perceptions and curricular experience of environmentally sustainable practice which was adapted from previously published surveys. The invitation with survey link was disseminated via social media, Australian pharmacy student organisations, and direct approach. Quantitative data were reported descriptively. Qualitative data from responses to open-ended questions were analysed thematically using a reflexive, recursive approach. Incomplete survey responses were excluded from the analysis. Results: Of the 164 complete responses, 99% had previously received information on environmental sustainability. However, only 10% were knowledgeable about ESPP and only 8.5% were aware of ESPP content in their pharmacy school curriculum. Importantly, 70% of respondents saw ESPP as relevant to their future pharmacy practice, and 94% believed the pharmacy profession has a responsibility to undertake sustainability initiatives in the delivery of pharmaceutical care. Conclusions: Australian pharmacy students lacked knowledge of ESPP and few reported having curricular exposure to ESPP content in their pharmacy degrees. Therefore, ESPP content is an important area for development in pharmacy curricula.

Medication Regimen Complexity and Risk of Bleeding in People Who Initiate Oral Anticoagulants for Atrial Fibrillation: A Population-Based Study.

BACKGROUND: Oral anticoagulants (OACs) are high-risk medications often used in older people with complex medication regimens. This study was the first to assess the association between overall regimen complexity and bleeding in people with atrial fibrillation (AF) initiating OACs. METHODS: Patients diagnosed with AF who initiated an OAC (warfarin, dabigatran, rivaroxaban, apixaban) between 2010 and 2016 were identified from the Hong Kong Clinical Database and Reporting System. Each patient's Medication Regimen Complexity Index (MRCI) score was computed. Baseline characteristics were balanced using inverse probability of treatment weighting. People were followed until a first hospitalization for bleeding (intracranial hemorrhage, gastrointestinal bleeding, or other bleeding) and censored at discontinuation of the index OAC, death, or end of the follow-up period, whichever occurred first. Cox regression was used to estimate hazard ratios (HR) between MRCI quartiles and bleeding during initiation and all follow-up. RESULTS: There were 19 292 OAC initiators (n = 9 092 warfarin, n = 10 200 direct oral anticoagulants) with a mean (standard deviation) age at initiation of 73.9 (11.0) years. More complex medication regimens were associated with an increased risk of bleeding (MRCI > 14.0-22.00: aHR 1.17, 95% confidence interval [CI] 0.93-1.49; MRCI > 22.0-32.5: aHR 1.32, 95%CI 1.06-1.66; MRCI > 32.5: aHR 1.45, 95%CI 1.13-1.87, compared to MRCI ≤ 14). No significant association between MRCI and bleeding risk was observed during the initial 30, 60, or 90 days of treatment. CONCLUSION: In this cohort study of people with AF initiating an OAC, a more complex medication regimen was associated with higher bleeding risk over periods longer than 90 days. Further prospective studies are needed to assess whether MRCI should be considered in OAC prescribing.

Impact of Medication Regimen Simplification on Medication Incidents in Residential Aged Care: SIMPLER Randomized Controlled Trial.

In the SImplification of Medications Prescribed to Long-tErm care Residents (SIMPLER) cluster-randomized controlled trial, we investigated the impact of a structured medication regimen simplification intervention on medication incidents in residential aged care facilities (RACFs) over a 12-month follow-up. A clinical pharmacist applied the validated 5-step Medication Regimen Simplification Guide for Residential Aged CarE (MRS GRACE) for 96 of the 99 participating residents in the four intervention RACFs. The 143 participating residents in the comparison RACFs received usual care. Over 12 months, medication incident rates were 95 and 66 per 100 resident-years in the intervention and comparison groups, respectively (adjusted incident rate ratio (IRR) 1.13; 95% confidence interval (CI) 0.53-2.38). The 12-month pre/post incident rate almost halved among participants in the intervention group (adjusted IRR 0.56; 95%CI 0.38-0.80). A significant reduction in 12-month pre/post incident rate was also observed in the comparison group (adjusted IRR 0.67, 95%CI 0.50-0.90). Medication incidents over 12 months were often minor in severity. Declines in 12-month pre/post incident rates were observed in both study arms; however, rates were not significantly different among residents who received and did not receive a one-off structured medication regimen simplification intervention.

Medication administration in Australian residential aged care: A time-and-motion study.

RATIONALE/AIM: Medication administration is a complex and time-consuming task in residential aged care facilities (RACFs). Understanding the time associated with each administration step may help identify opportunities to optimize medication management in RACFs. This study aimed to investigate the time taken to administer medications to residents, including those with complex care needs such as cognitive impairment and swallowing difficulties. METHOD: A time-and-motion study was conducted in three South Australian RACFs. A representative sample of 57 scheduled medication administration rounds in 14 units were observed by a single investigator. The rounds were sampled to include different times of day, memory support units for residents living with dementia and standard units, and medication administration by registered and enrolled nurses. Medications were administered from pre-prepared medication strip packaging. The validated Work Observation Method By Activity Timing (WOMBAT) software was used to record observations. RESULTS: Thirty nurses were observed. The average time spent on scheduled medication administration rounds was 5.2 h/unit of average 22 residents/day. The breakfast medication round had the longest duration (1.92 h/unit). Resident preparation, medication preparation and provision, documentation, transit, communication, and cleaning took an average of 5 minutes per resident per round. Medication preparation and provision comprised 60% of overall medication round time and took significantly longer in memory support than in standard units (66 vs 49 seconds per resident per round for preparation, 79 vs 58 for provision; P < .001 for both). Almost half (42%) of tablets/capsules were crushed in memory support units. The time taken for medication administration was not significantly different among registered and enrolled nurses. CONCLUSIONS: Nurses took an average of 5 minutes to administer medications per resident per medication round. Medication administration in memory support units took an additional minute per resident per round, with almost half of tablets and capsules needing to be crushed.

Process Evaluation of the SImplification of Medications Prescribed to Long-tErm Care Residents (SIMPLER) Cluster Randomized Controlled Trial: A Mixed Methods Study.

Complex medication regimens are highly prevalent, burdensome for residents and staff, and associated with poor health outcomes in residential aged care facilities (RACFs). The SIMPLER study was a non-blinded, matched-pair, cluster randomized controlled trial in eight Australian RACFs that investigated the one-off application of a structured 5-step implicit process to simplify medication regimens. The aim of this study was to explore the processes underpinning study implementation and uptake of the medication simplification intervention. A mixed methods process evaluation with an explanatory design was undertaken in parallel with the main outcome evaluation of the SIMPLER study and was guided by an established 8-domain framework. The qualitative component included a document analysis and semi-structured interviews with 25 stakeholders (residents, family, research nurses, pharmacists, RACF staff, and a general medical practitioner). Interviews were transcribed verbatim and reflexively thematically content analyzed. Descriptive statistics were used to summarize quantitative data extracted from key research documents. The SIMPLER recruitment rates at the eight RACFs ranged from 18.9% to 48.6% of eligible residents (38.4% overall). Participation decisions were influenced by altruism, opinions of trusted persons, willingness to change a medication regimen, and third-party hesitation regarding potential resident distress. Intervention delivery was generally consistent with the study protocol. Stakeholders perceived regimen simplification was beneficial and low risk if the simplification recommendations were individualized. Implementation of the simplification recommendations varied between the four intervention RACFs, with simplification implemented at 4-month follow-up for between 25% and 86% of residents for whom simplification was possible. Good working relationships between stakeholders and new remunerated models of medication management were perceived facilitators to wider implementation. In conclusion, the one-off implicit medication simplification intervention was feasible and generally delivered according to the protocol to a representative sample of residents. Despite variable implementation, recommendations to simplify complex regimens were valued by stakeholders, who also supported wider implementation of medication simplification in RACFs.

Reducing the Burden of Complex Medication Regimens: SImplification of Medications Prescribed to Long-tErm care Residents (SIMPLER) Cluster Randomized Controlled Trial.

OBJECTIVE: To assess the application of a structured process to consolidate the number of medication administration times for residents of aged care facilities. DESIGN: A nonblinded, matched-pair, cluster randomized controlled trial. SETTING AND PARTICIPANTS: Permanent residents who were English-speaking and taking at least 1 regular medication, recruited from 8 South Australian residential aged care facilities (RACFs). METHODS: The intervention involved a clinical pharmacist applying a validated 5-step tool to identify opportunities to reduce medication complexity (eg, by administering medications at the same time or through use of longer-acting or combination formulations). Residents in the comparison group received routine care. The primary outcome at 4-month follow-up was the number of administration times per day for medications charted regularly. Resident satisfaction and quality of life were secondary outcomes. Harms included falls, medication incidents, hospitalizations, and mortality. The association between the intervention and primary outcome was estimated using linear mixed models. RESULTS: Overall, 99 residents participated in the intervention arm and 143 in the comparison arm. At baseline, the mean resident age was 86 years, 74% were female, and medications were taken an average of 4 times daily. Medication simplification was possible for 62 (65%) residents in the intervention arm, with 57 (62%) of 92 simplification recommendations implemented at follow-up. The mean number of administration times at follow-up was reduced in the intervention arm in comparison to usual care (-0.36, 95% confidence interval -0.63 to -0.09, P = .01). No significant changes in secondary outcomes or harms were observed. CONCLUSIONS AND IMPLICATIONS: One-off application of a structured tool to reduce regimen complexity is a low-risk intervention to reduce the burden of medication administration in RACFs and may enable staff to shift time to other resident care activities.

Process, impact and outcomes of medication review in Australian residential aged care facilities: A systematic review.

OBJECTIVE: To systematically review literature reporting processes, impact and outcomes of medication review and reconciliation in Australian residential aged care facilities (RACFs). METHODS: PubMed/MEDLINE, EMBASE, CINAHL, Informit Health and grey literature were searched from 1995 to July 2018. Studies reporting outcomes of a stand-alone medication review or reconciliation interventions in Australian RACFs were included. RESULTS: Thirteen studies investigated medication review, eight of which studied Residential Medication Management Reviews (RMMRs). Five studies reported that medication reviews identified an average of 2.7-3.9 medication-related problems (MRPs) per resident. One study reported medication reviews had no impact on quality of life, hospitalisation or mortality, but was not powered to assess these. Three studies reported general practitioners' acceptance of pharmacists' recommendations to resolve MRPs, ranging between 45 and 84%. CONCLUSIONS: Medication review may be a useful strategy to identify and prompt resolution of MRPs. However, the impact on clinical and resident-centred outcomes remains unclear.

Protocol for a non-randomised pilot and feasibility study evaluating a multicomponent intervention to simplify medication regimens for people receiving community-based home care services.

INTRODUCTION: Managing medication regimens is one of the most complex and burdensome tasks performed by older people, and can be prone to errors. People living with dementia may require medication administration assistance from formal and informal caregivers. Simplified medication regimens maintain the same therapeutic intent, but have less complex instructions and administration schedules. This protocol paper outlines a study to determine the feasibility of a multicomponent intervention to simplify medication regimens for people receiving community-based home care services. METHODS AND ANALYSIS: This is a non-randomised pilot and feasibility study. Research nurses will recruit 50 people receiving community-based home care services. All participants will receive the intervention from a clinical pharmacist, who will undertake medication reconciliation, assess each participant's capacity to self-manage their medication regimen and apply a structured tool to identify opportunities for medication simplification. The pharmacist will communicate recommendations regarding medication simplification to registered nurses at the community-based home care provider organisation. The primary outcome will be a description of study feasibility (recruitment and retention rates, protocol adherence and stakeholder acceptability). Secondary outcomes include the change in number of medication administration times per day, medication adherence, quality of life, participant satisfaction, medication incidents, falls and healthcare utilisation at 4 months. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Monash University Human Research Ethics Committee and the community-based home care provider organisation's ethical review panel. Research findings will be disseminated to consumers and caregivers, health professionals, researchers and healthcare providers through the National Health and Medical Research Council Cognitive Decline Partnership Centre and through conference presentations, lay summaries and peer-reviewed publications. This study will enable an improved understanding of medication management and administration among people receiving community-based home care services. This study will inform the decision to proceed with a randomised controlled trial to assess the effect of this intervention. TRIAL REGISTRATION NUMBER: ACTRN12618001130257; Pre-results.

Medications and Prescribing Patterns as Factors Associated with Hospitalizations from Long-Term Care Facilities: A Systematic Review.

BACKGROUND: Residents of long-term care facilities (LTCFs) are at high risk of hospitalization. Medications are a potentially modifiable risk factor for hospitalizations. OBJECTIVE: Our objective was to systematically review the association between medications or prescribing patterns and hospitalizations from LTCFs. METHODS: We searched MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and International Pharmaceutical Abstracts (IPA) from inception to August 2017 for longitudinal studies reporting associations between medications or prescribing patterns and hospitalizations. Two independent investigators completed the study selection, data extraction and quality assessment using the Joanna Briggs Institute Critical Appraisal Tools. RESULTS: Three randomized controlled trials (RCTs), 22 cohort studies, five case-control studies, one case-time-control study and one case-crossover study, investigating 13 different medication classes and two prescribing patterns were included. An RCT demonstrated that high-dose influenza vaccination reduced all-cause hospitalization compared with standard-dose vaccination (risk ratio [RR] 0.93; 95% confidence interval [CI] 0.88-0.98). Another RCT found no difference in hospitalization rates between oseltamivir as influenza treatment and oseltamivir as treatment plus prophylaxis (treatment = 4.7%, treatment and prophylaxis = 3.5%; p = 0.7). The third RCT found no difference between multivitamin/mineral supplementation and hospitalization (odds ratio [OR] 0.94; 95% CI 0.74-1.20) or emergency department visits (OR 1.05; 95% CI 0.76-1.47). Two cohort studies demonstrated influenza vaccination reduced hospitalization. Four studies suggested polypharmacy and potentially inappropriate medications (PIMs) increased all-cause hospitalization. However, associations between polypharmacy (two studies), PIMs (one study) and fall-related hospitalizations were inconsistent. Inconsistent associations were found between psychotropic medications with all-cause and cause-specific hospitalizations (11 studies). Warfarin, nonsteroidal anti-inflammatory drugs, pantoprazole and vinpocetine but not long-term acetylsalicylic acid (aspirin), statins, trimetazidine, digoxin or ß-blockers were associated with all-cause or cause-specific hospitalizations in single studies of specific resident populations. Most cohort studies assessed prevalent rather than incident medication exposure, and no studies considered time-varying medication use. CONCLUSION: High-quality evidence suggests influenza vaccination reduces hospitalization. Polypharmacy and PIMs are consistently associated with increased all-cause hospitalization.

SImplification of Medications Prescribed to Long-tErm care Residents (SIMPLER): study protocol for a cluster randomised controlled trial.

BACKGROUND: Complex medication regimens are highly prevalent in residential aged care facilities (RACFs). Strategies to reduce unnecessary complexity may be valuable because complex medication regimens can be burdensome for residents and are costly in terms of nursing time. The aim of this study is to investigate application of a structured process to simplify medication administration in RACFs. METHODS: SImplification of Medications Prescribed to Long-tErm care Residents (SIMPLER) is a non-blinded, matched-pair, cluster randomised controlled trial of a single multidisciplinary intervention to simplify medication regimens. Trained study nurses will recruit English-speaking, permanent residents from eight South Australian RACFs. Medications taken by residents in the intervention arm will be assessed once using a structured tool (the Medication Regimen Simplification Guide for Residential Aged CarE) to identify opportunities to reduce medication regimen complexity (e.g. by administering medications at the same time, or through the use of longer-acting or combination formulations). Residents in the comparison group will receive routine care. Participants will be followed for up to 36 months after study entry. The primary outcome measure will be the total number of charted medication administration times at 4 months after study entry. Secondary outcome measures will include time spent administering medications, medication incidents, resident satisfaction, quality of life, falls, hospitalisation and mortality. Individual-level analyses that account for clustering will be undertaken to determine the impact of the intervention on the study outcomes. DISCUSSION: Ethical approval has been obtained from the Monash University Human Research Ethics Committee and the aged care provider organisation. Research findings will be disseminated through conference presentations and peer-reviewed publications. SIMPLER will enable an improved understanding of the burden of medication use in RACFs and quantify the impact of regimen simplification on a range of outcomes important to residents and care providers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12617001060336 . Retrospectively registered on 20 July 2017.

Spontaneously reported haemorrhagic adverse events associated with rivaroxaban and dabigatran in Australia.

OBJECTIVES: The objective of our study was to describe spontaneously reported haemorrhagic adverse events associated with rivaroxaban and dabigatran in Australia. METHODS: Data were sourced from the Australian Therapeutic Goods Administration (TGA) Database of Adverse Event Notifications between June 2009 and May 2014. Records of haemorrhagic adverse events in which rivaroxaban or dabigatran was considered as a potential cause were analysed. RESULTS: There were 240 haemorrhagic adverse events associated with rivaroxaban and 504 associated with dabigatran. Age was specified for 164 (68%) haemorrhages associated with rivaroxaban, of which 101 occurred in people aged ⩾75 years. Age was specified for 437 (87%) haemorrhages associated with dabigatran, of which 300 occurred in people aged ⩾75 years. Time from treatment initiation to haemorrhage was specified for 122 (51%) haemorrhages associated with rivaroxaban, with 69 (57%) haemorrhages occurring within 30 days of rivaroxaban initiation. Time from treatment initiation to haemorrhage was specified for 253 (50%) haemorrhages associated with dabigatran, with 123 (49%) haemorrhages occurring within 30 days of dabigatran initiation. Gastrointestinal (GI) haemorrhages were the most frequent type of haemorrhages associated with both rivaroxaban (n = 105, 44%) and dabigatran (n = 302, 60%). Data were available on the severity of haemorrhage for 101 (42%) haemorrhages associated with rivaroxaban, with haemorrhage leading to death in 17 people. The severity of haemorrhage was specified for 384 (76%) haemorrhages associated with dabigatran, with haemorrhage leading to death in 61 people. CONCLUSIONS: Our study highlights the need for research on the haemorrhagic complications of anticoagulation in clinical care. A considerable proportion of reported haemorrhagic events occurred within 30 days of rivaroxaban and dabigatran initiation. This highlights the importance of considering bleeding risk at the time of treatment initiation.