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Introduction: Primary care provides an opportunity to prevent community acquired, medicine or drug-induced acute kidney injury. One of the barriers to proactive prevention of medicine-induced kidney injury in primary care is the lack of a list of nephrotoxic medicines that are most problematic in primary care, particularly one that provides a comparison of risks across medicines.Objective: The aim of this study was to consolidate evidence on the risks associated with medicines and acute kidney injury, with a focus on medicines used in primary care.Method: We searched the MEDLINE and EMBASE databases to identify published studies of all medicines associated with acute kidney injury identified from spontaneous report data. For each medicine positively associated with acute kidney injury, as identified from spontaneous reports, we implemented a sequence symmetry analysis (SSA) and a case-control design to determine the association between the medicine and hospital admission with a primary diagnosis of acute kidney injury (representing community-acquired acute kidney injury). Administrative claims data held by the Australian Government Department of Veterans' Affairs for the study period 2005-2019 were used.Results: We identified 89 medicines suspected of causing acute kidney injury based on spontaneous report data and a reporting odds ratio above 2, from Japan, France and the US. Spironolactone had risk estimates of 3 or more based on spontaneous reports, SSA and case-control methods, while furosemide and trimethoprim with sulfamethoxazole had risk estimates of 1.5 or more. Positive association with SSA and spontaneous reports, but not case control, showed zoledronic acid had risk estimates above 2, while candesartan telmisartan, simvastatin, naproxen and ibuprofen all had risk estimates in SSA between 1.5 and 2. Positive associations with case-control and spontaneous reports, but not SSA, were found for amphotericin B, omeprazole, metformin, amlodipine, ramipril, olmesartan, ciprofloxacin, valaciclovir, mycophenolate and diclofenac. All with the exception of metformin and omeprazole had risk estimates above 2.Conclusion: This research highlights a number of medicines that may contribute to acute injury; however, we had an insufficient sample to confirm associations of some medicines. Spironolactone, furosemide, and trimethoprim with sulfamethoxazole are medicines that, in particular, need to be used carefully and monitored closely in patients in the community at risk of acute kidney injury. [ABSTRACT FROM AUTHOR]

Objective To assess the effectiveness of a pharmacist-led intervention using validated tools to reduce medicine-induced deterioration and adverse reactions. Design and setting Multicenter, open-label parallel randomised controlled trial involving 39 Australian aged-care facilities. Participants Residents on ≥4 medicines or ≥1 anticholinergic or sedative medicine. Intervention Pharmacist-led intervention using validated tools to detect signs and symptoms of medicine-induced deterioration which occurred every 8 weeks over 12 months. Comparator Usual care (Residential Medication Management Review) provided by accredited pharmacists. Outcomes Primary outcome was change in Frailty Index at 12 months. Secondary outcomes included changes in cognition, 24-hour movement behaviour by accelerometry, grip strength, weight, adverse events and quality of life. Results 248 persons (median age 87 years) completed the study; 120 in the interventionand, 128 in control arms. In total 575 pharmacist, sessions were undertaken in the intervention arm. There was no statistically significant difference for change in frailty between groups (mean difference: 0.009, 95% CI: −0.028, 0.009, P  = 0.320). A significant difference for cognition was observed, with a mean difference of 1.36 point change at 12 months (95% CI: 0.01, 2.72, P  = 0.048). Changes in 24-hour movement behaviour, grip strength, adverse events and quality of life were not significantly different between groups. Point estimates favoured the intervention arm at 12 months for frailty, 24-hour movement behaviour and grip strength. Conclusions The use of validated tools by pharmacists to detect signs of medicine-induced deterioration is a model of practice that requires further research, with promising results from this trial, particularly with regards to improved cognition. [ABSTRACT FROM AUTHOR]

Introduction: Medicines acting on the central nervous system can increase the risk of postoperative delirium, but the specific medicines associated with greatest risk remain unclear. Objectives: We aimed to examine the risk of individual central nervous system-acting medicines used preoperatively on delirium after hip or knee surgery. Methods: A matched case-control study was conducted using data from the Australian Government Department of Veterans' Affairs. We included people aged 65 years or older who had knee or hip surgery between 2000 and 2019. People with hip or knee surgery who developed postoperative delirium were cases and controls were people with hip or knee surgery but who did not develop postoperative delirium. Use of medicines including anxiolytics, sedatives, and hypnotics, opioid analgesics and antidepressants prior to surgery was compared between cases and controls. Results: A total of 2614 patient cases with postoperative delirium were matched by same sex, age (±2 years), and year of admission (±2 years) with 7842 controls without postoperative delirium. Cases were more likely to be exposed to nitrazepam (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.24–2.64), sertraline (OR = 1.50, 95% CI 1.20–1.87), mirtazapine (OR = 1.38, 95% CI 1.11–1.74), venlafaxine (OR = 1.42, 95% CI 1.02–1.98), citalopram (OR = 1.54, 95% CI 1.19–1.99), escitalopram (OR = 1.42, 95% CI 1.06–1.89) or fluvoxamine (OR = 5.01, 95% CI 2.15–11.68) prior to surgery than controls. At the class level, exposure to benzodiazepines (OR = 1.20, 95% CI 1.05–1.37) and antidepressants (OR = 1.64, 95% CI 1.47–1.83) prior to surgery was significantly higher in cases than in controls. The numbers needed to treat to harm for one additional delirium case were 43 for sertraline, 40 for citalopram, 57 for mirtazapine and 26 for nitrazepam. Whereas, the numbers needed to treat to harm were found to be 20 for sertraline, 17 for citalopram, 19 for mirtazapine and 10 for nitrazepam in the 85 years or older age group, indicating that the harmful effect of these medicines is pronounced as age advances. Conclusions: People who developed delirium following hip or knee surgery were more likely to be exposed to nitrazepam, sertraline, mirtazapine, venlafaxine, citalopram, escitalopram or fluvoxamine at the time of admission for surgery. Planning to reduce use of these medicines well prior to surgery may decrease the risk of postoperative delirium. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the utilization of Alzheimer's disease (AD) treatments, donepezil, galantamine, rivastigmine, and memantine, in Korea with Australia and other countries with universal health coverage. Methods: Reimbursement criteria and the patent status of four AD treatments in Korea and Australia were reviewed. The monthly spending and utilization of the treatments were extracted from the national electronic database in Korea and Australia. The defined daily dose per 1000 elderly population per day (DDD/1000e/day) were calculated from July 2008 to June 2019. Annual cost trends of Norway and England were compared with Korea and Australia. Results: With the highest share of the use of donepezil in both countries, the cost and utilization of AD treatments in Korea increased more rapidly and remained higher than Australia. The cost of AD treatments in Korea increased by 15.5% every year during the study period, while the spending of the same drugs in Australia decreased by 10.5% annually. The utilization in DDD/1000e/day of AD treatments in Korea increased by 18.3% annually compared with 1.4% in Australia. When compared with Norway and England, countries with similar universal health coverage (UHC) system and elderly polupation, the cost of AD treatments in Korea was still higher with the opposite trend from other countries. Conclusions: Despite the similar UHC systems, there were considerable differences in the post-market utilization of AD treatments in Korea from Australia and other countries. This results can be attributed to differences in re-assessment system, pricing and reimbursement policies, and prescribing culture. This study provides a baseline to explore more comprehensive cross-country studies on rational use of medicines. [ABSTRACT FROM AUTHOR]

Background: The case-crossover design is suited to medication safety studies but is vulnerable to exposure misclassification. Using the example of tricyclic antidepressants and the risk of hip fracture, we present a data visualisation tool for observing exposure misclassification in case-crossover studies.Methods: A case-crossover study was conducted using Australian Government Department of Veterans' Affairs claims data. Beneficiaries aged over 65 years who were hospitalised for hip fracture between 2009 and 2012 were included. The case window was defined as 1-50 days pre fracture. Control window one and control window two were defined as 101-150 and 151-200 days pre fracture, respectively. Patients were stratified by whether exposure status changed when control window two was specified instead of control window one. To visualise potential misclassification, each subject's tricyclic antidepressant dispensings were plotted over the 200 days pre fracture.Results: The study population comprised 8828 patients with a median age of 88 years. Of these subjects, 348 contributed data to the analyses with either control window. The data visualisation suggested that 14% of subjects were potentially misclassified with control window one while 45% were misclassified with control window two. The odds ratio for the association between tricyclic antidepressants and hip fracture was 1.18 (95% confidence interval = 0.91-1.52) using control window one, whereas risk was significantly increased (odds ratio = 1.43, 95% confidence interval = 1.11-1.83) using control window two.Conclusions: Exposure misclassification was less likely to be present with control window one than with an earlier control window, control window two. When specifying different control windows in a case-crossover study, data visualisation can help to assess the extent to which exposure misclassification may contribute to variable results. [ABSTRACT FROM AUTHOR]

Objectives To examine the risk of dementia associated with posttraumatic stress disorder ( PTSD) and the contribution of antipsychotic use to this risk. Design Retrospective cohort study Setting Australia. Administrative claims data from the Australian Government Department of Veterans' Affairs were used. Participants Male Vietnam veterans aged 55 to 65 at baseline (2001-02) with no preexisting dementia diagnosis (N = 15,612). Measurements The association between PTSD and dementia was assessed over 12 years of follow-up. Dementia was identified as a hospital diagnosis, dementia record in service disability data, or dispensing of medicines for dementia. Cox-proportional hazards models were used, with age as the time-scale. Results were stratified according to baseline antipsychotic use. Results No greater risk of dementia was observed with PTSD. In veterans who received antipsychotics, dementia risk was significantly higher than in those who did not (hazard ratio ( HR) = 2.1, 95% confidence interval ( CI) = 1.4-3.3). Dementia risk was significantly greater in veterans hospitalized for PTSD who received antipsychotics ( HR = 2.2, 95% CI = 1.1-4.6) and veterans without PTSD who received antipsychotics ( HR = 4.3, 95% CI = 2.1-8.6) than in those without PTSD with no antipsychotic use. Conclusion Antipsychotic use may be a contributor to dementia risk. These findings should be interpreted with caution because the study design was observational. Further research using prospective study designs in settings where diagnostic data, cognitive function, and disease severity are available are required. [ABSTRACT FROM AUTHOR]

Aims To determine the frequency, timing and patterns of endocrine therapy switching in Australian practice for postmenopausal women with primary breast cancer. Methods We identified postmenopausal women in a population-based cohort commencing endocrine therapy for invasive primary breast cancer between December 2005 and December 2008 ( n = 645). Individual-level administrative health records and self-report data were used to determine women's demographic and clinical characteristics, including preexisting and newly-treated comorbidities, and switches in endocrine therapy. Time to therapy switching was calculated. Chi-square tests compared the characteristics of women who did and did not switch, and those switching within 2 years or after 2 years of commencing therapy. Results Twenty-eight percent of women switched from their initial endocrine therapy, most commonly from tamoxifen to anastrozole, or the converse. A small number of anastrozole-to-exemestane and letrozole-to-exemestane switches were observed ( n = 19). Most women (>80%) who switched therapies did not have newly-treated comorbidities. Few women (<5%) switched before completing 2 years of therapy, but these women were significantly more likely to have preexisting antidepressant use than women switching later (43% vs 23%, P = 0.048) and remained on the subsequent therapy for less time (6 months vs 2.7 years, P < 0.001). Conclusions Approximately one-quarter of postmenopausal women with primary breast cancer switched endocrine therapies. The findings suggest that the majority of switching in Australian practice was planned; occurring after 2-3 years of, not precipitated by comorbidity, and in a sequence supported by trial evidence. Early switching, however, was associated with preexisting depression and appeared to be a marker of poor persistence. [ABSTRACT FROM AUTHOR]

Aim: To provide an estimate of the numbers of medication errors and adverse drug reactions that occur along a person's journey through their hospital stay in Australia. Methods: A search of databases and online resources was undertaken to identify published literature on medication safety in the acute care setting in Australia from 2008 to 2013. Data on the rates of adverse drug reactions and medication errors associated with hospitalization was extracted from the published studies. This evidence was synthesized with evidence from previous reviews of medication safety in the acute care setting in Australia conducted in 2002 and 2008. Results: Findings from the Australian literature across the two previous reviews of medication safety and the present review indicate the proportion of all hospital admissions that are medication-related is between 2 and 3%. Studies assessing medication errors on admission to hospital suggest there may be an overall rate of two errors for every three patients at the time of admission to hospital. Large studies examining the rates of prescribing errors in major Australian teaching hospitals give insight into the rates of prescription error and suggest that prescription error rates of up to one error per patient occur in the hospital system. The best available evidence from more recent research suggests that errors (excluding errors of timing) occur in around 9% of medication administrations in hospital. At hospital discharge, errors in medication documentation in discharge summaries may occur at a rate of up to two errors per patient. Conclusions: Medication safety in the various stages of the patient journey through acute care in Australia continues to be a significant problem. However, the extent of medication-related problems in acute care needs to be interpreted within the context of increasingly complex health care. There are an estimated 230 000 medication-related hospital admissions occurring per year. This suggests an annual cost of medication-related admissions of AU$1.2 billion. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of polymorphisms among the metabolising enzymes and pharmacodynamic receptors relevant for the thiazolidinediones differs by ethnic group, a factor that may modify risk of adverse drug events.Objective: The aim of the study was to determine if the risk of oedema or heart failure associated with the thiazolidinediones varies in populations in Australia, Canada, Hong Kong, Japan, Korea and Taiwan.Methods: Sequence symmetry analyses were undertaken to investigate the risk of peripheral oedema, as measured by incident furosemide dispensing, and risk of hospitalisations for heart failure. Results were pooled, with Australia and Canada representing predominantly Caucasian population and all other countries contributing to Asian population estimates.Results: Pooled estimates of risk for furosemide initiation in the Caucasian populations were significantly increased for pioglitazone [adjusted sequence ratio (ASR) 1.47; 95 % confidence interval (CI) 1.14-1.91] and rosiglitazone (ASR 1.65; 95 % CI 1.58-1.72), while in the Asian populations, the pooled risk estimates were lower (ASR 1.11; 95 % CI 0.93-1.32 and ASR 1.21; 95 % CI 1.01-1.45 for pioglitazone and rosiglitazone, respectively). Results for hospitalisation for heart failure showed a similar trend, with elevated risk in the Australian data (ASR 1.88; 95 % CI 1.01-3.5 and ASR 1.25; 95 % CI 0.76-2.05 for pioglitazone and rosiglitazone, respectively), while no increased risk was found in the pooled results for the Asian populations.Conclusion: The risk of both oedema and heart failure with thiazolidinediones was higher in predominantly Caucasian countries than in the Asian countries assessed. Assessment of adverse events by ethnicity may support safer medicine use. [ABSTRACT FROM AUTHOR]

Background The Australian Government Department of Veterans' Affairs (DVA) funds an ongoing health promotion based program to improve use of medicines and related health services, which implements interventions that include audit and feedback in the form of patient-specific feedback generated from administrative claims records. We aimed to determine changes in medicine use as a result of the program. Methods The program provides targeted patient-specific feedback to medical practitioners. The feedback is supported with educational material developed by a clinical panel, subject to peer review and overseen by a national editorial committee. Veterans who meet target criteria also receive educational brochures. The program is supported by a national call centre and ongoing national consultation. Segmented regression analyses (interrupted time series) were undertaken to assess changes in medication use in targeted veterans pre and post each intervention. Results 12 interventions were included; three to increase medicine use, seven which aimed to reduce use, and two which had combination of messages to change use. All programs that aimed to increase medicine use were effective, with relative effect sizes at the time of the intervention ranging from 1% to 8%. Mixed results were seen with programs aiming to reduce inappropriate medicine use. Highly specific programs were effective, with relative effect sizes at the time of the intervention of 10% decline in use of NSAIDs in high risk groups and 14% decline in use of antipsychotics in dementia. Interventions targeting combinations of medicines, including medicine interactions and potentially inappropriate medicines in the elderly did not change practice significantly. Interventions with combinations of messages targeting multiple components of practice had an impact on one component, but not all components targeted. Conclusions The Veterans' MATES program showed positive practice change over time, with interventions increasing use of appropriate medicines where under-use was evident and reduced use of inappropriate medicines when single medicines were targeted. Combinations of messages were less effective, suggesting specific messages focusing on single medicines are required to maximise effect. The program provides a model that could be replicated in other settings. [ABSTRACT FROM AUTHOR]

Purpose: To identify the extent of use of medicines recommended to be used with caution in glaucoma patients with specified comorbidities and to determine evidence of associated harm. Methods: Retrospective cohort analysis from administrative claims data and prescription/event sequence symmetry analysis. Participants: Australian Government Department of Veterans' Affairs treatment card holders dispensed glaucoma eye-drops. Main outcome measures: Proportion of veterans with glaucoma and diabetes, airways disease, heart failure, ischemic heart disease or depression, dispensed glaucoma eye drops which should be used with caution. For harms, outcome measures were hospitalizations for airways disease and heart disease. Results: The cohort analysis included 25,984 veterans. Of these, 88% with airways disease were dispensed glaucoma eye drops with the potential to aggravate airways disease, 43% with heart failure were dispensed topical beta-blockers and 49% with depression received glaucoma eye drops which should be used cautiously in those with depression. We found increased risk of initiation of inhaled beta-agonist following timolol (adjusted sequence ratio (ASR) 1.48, 99% CI 1.22-1.78) and latanoprost (ASR 1.24, 99% CI 1.11-1.38) initiation. We found increased risk of inhaled corticosteroid initiation following initiation of timolol (ASR 1.43, 99% CI 1.13-1.81). There was increased risk of antidepressant initiation following timolol initiation (ASR 1.24, 99% CI 1.07-1.43), and latanoprost (ASR 1.16, 99% CI 1.03-1.31). There was also increased risk of hospitalization for bradycardia following timolol initiation (ASR 2.22,99% CI 1.15-4.31). Conclusion: Use of glaucoma eye drops recommended to be used with caution in co-morbidities is common and was associated with adverse outcomes. Awareness of co-morbidities is required in the selection and prescription of glaucoma eye drops. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics are frequently and increasingly prescribed to treat the behavioural symptoms associated with dementia despite their modest efficacy. Evidence regarding the potential adverse events of antipsychotics is limited and little is known about the longer-term safety of these medicines in the elderly. The aim of this review was to determine the impact of the choice of observational study design and methods used to control for confounding on the measurement of antipsychotic risks in elderly patients. Methods: We searched PUBMED and the Cochrane controlled trials register for double-blind randomised controlled trials (RCTs), meta-analyses and published observational studies of antipsychotics. Results: Forty four studies were identified for the endpoints; death, cerebrovascular events, hip fracture and pneumonia. RCTs found a 20% to 30% increased risk of death, or an absolute increase of 1extra death per 100 patients with atypical antipsychotics compared to non-use. Cohort and instrumental variable analyses estimated between 2 to 7 extra deaths per 100 patients with conventional compared to atypical antipsychotics. RCTs found a 2 to 3 times increased risk of all cerebrovascular events with atypical antipsychotics compared to placebo and no association with serious stroke that required hospitalisation. Observational studies using cohort and self-controlled case-series designs reported similar results; no association where the endpoint was stroke causing hospitalisation and a doubling of risk when minor stroke was included. No RCTs were available for the outcome of hip fracture or pneumonia. Observational studies reported a 20% to 40% increased risk of hip fracture with both antipsychotic classes compared to non-use. The risk of pneumonia was a 2 to 3 times greater with both classes compared to non-use while a self-controlled case-series study estimated a 60% increased risk. Conventional antipsychotics were associated with a 50% greater hip fracture risk than atypical antipsychotics, while the risk of pneumonia was similar between the classes. Conclusions: Choice of observational study design is critical in studying the adverse effects of antispychotics. Cohort and instrumental variable analyses gave more consistent results to clinical studies for mortality outcomes as have self-controlled case-series for the risk of cerebrovascular events and stroke. Observational evidence has highlighted the potential for antipsychotics to be associated with serious adverse events that were not reported in RCTs including hip fracture and pneumonia. Good quality observational studies are required, that employ appropriate study designs that are robust towards unmeasured confounding, to confirm the potential excess risk of hip fracture and pneumonia with antipsychotics. [ABSTRACT FROM AUTHOR]

Background: Co-morbidity of both cardiac and non-cardiac conditions is common in the elderly with heart failure (HF) and can be associated with adverse clinical outcomes. Objectives: The aims of this study were to examine the prevalence of comorbidity and potential treatment conflicts that may result in adverse clinical outcomes in a large cohort of elderly HF patients. Methods: We conducted a cross-sectional study using administrative claims data (1 April to 31 July 2007) from the Department of Veterans' Affairs, Australia, on all veterans aged ≥65 years with HF. Co-morbidities were defined using the pharmaceutical based co-morbidity index Rx-Risk-V. Potential treatment conflicts for patients with HF and co-morbid diseases were identified from Australian clinical guidelines or reference compendia and their prevalence in the data were determined. Results: A total of 6730 patients were included in the study, with a median of 6 co-morbid conditions (interquartile range [IQR] 4-7) and 11 (IQR 8-15) unique medicines. Almost the entire HF cohort (97.8%) were identified as having at least one co-morbid condition that may cause a potential treatment conflict, with 55% having three or more. The conditions identified as being of greatest concern, based on their prevalence and potential for treatment conflict, were chronic airways disease, depression, chronic pain/inflammatory disease, glaucoma, diabetes mellitus and diseases treatable with corticosteroids. Conclusions: Potential treatment conflicts are common in the highly comorbid population of elderly patients with HF, and may influence the therapeutic management of not only HF but all conditions present. [ABSTRACT FROM AUTHOR]

Background: This study assessed whether the number of comorbid conditions unrelated to diabetes was associated with a delay in therapeutic progression of diabetes treatment in Australian veterans. Methodology/Principal Findings: A retrospective cohort study was undertaken using data from the Australian Department of Veterans' Affairs (DVA) claims database between July 2000 and June 2008. The study included new users of metformin or sulfonylurea medicines. The outcome was the time to addition or switch to another antidiabetic treatment. The total number of comorbid conditions unrelated to diabetes was identified using the pharmaceutical-based comorbidity index, Rx-Risk-V. Competing risk regression analyses were conducted, with adjustments for a number of covariates that included age, gender, residential status, use of endocrinology service, number of hospitalisation episodes and adherence to diabetes medicines. Overall, 20134 veterans were included in the study. At one year, 23.5% of patients with diabetes had a second medicine added or had switched to another medicine, with 41.4% progressing by 4 years. The number of unrelated comorbidities was significantly associated with the time to addition of an antidiabetic medicine or switch to insulin (subhazard ratio [SHR] 0.87 [95% CI 0.84-0.91], P,0.001). Depression, cancer, chronic obstructive pulmonary disease, dementia, and Parkinson's disease were individually associated with a decreased likelihood of therapeutic progression. Age, residential status, number of hospitalisations and adherence to anti-diabetic medicines delayed therapeutic progression. Conclusions/Significance: Increasing numbers of unrelated conditions decreased the likelihood of therapeutic progression in veterans with diabetes. These results have implications for the development of quality measures, clinical guidelines and the construction of models of care for management of diabetes in elderly people with comorbidities. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics are commonly used in the elderly despite a lack of safety data from randomized trials, particularly for the typical antipsychotics. Observational studies have investigated the association between antipsychotics and stroke but results vary, which may be due to lack of control for unmeasured confounding. Objective: To estimate the risk of hospitalization for stroke in elderly users of antipsychotics. Study Design and Setting: Using the Australian Government Department of Veterans' Affairs administrative claims dataset we utilized a self-controlled case series design to risk-adjust for potential unmeasured confounding. Risk periods prior to antipsychotic initiation were also included to search for evidence of confounding by indication. Unexposed patients were included to adjust for the increasing incidence of hospitalization for stroke with age. Results: There were 10638 patients aged ≥65 years with at least one hospitalization for stroke identified during the 4-year period from 1 January 2003 to 31 December 2006. Of these, 514 patients were initiated on typical anti-psychotics and 564 patients were initiated on atypical antipsychotics. Hospitalization for stroke was increased in the first week after initiation of a typical antipsychotic (incidence rate ratio [IRR] 2.3; 95% CI 1.3, 3.8). There was no evidence of an increased risk of hospitalization for stroke after initiation of atypical antipsychotics. The risk of hospitalization for stroke progressively increased in the weeks leading up to first-time antipsychotic treatment. However, while the risk of hospitalization for stroke in the week prior to initiating antipsychotic therapy was significantly increased for patients initiated on typical antipsychotics (IRR 7.2; 95% CI 5.3, 9.8), patients initiated on atypical antipsychotics had no excess risk in the same period (IRR 1.2; 95% CI 0.7, 2.3). Conclusions: The results of this study are consistent with randomized controlled trial evidence indicating that there is no increased risk of serious cerebrovascular events requiring hospitalization in patients taking atypical antipsychotics. No randomized controlled trial evidence is available on the risk of hospitalization for stroke with use of typical antipsychotics in the elderly. This study found a small but significantly increased risk of hospitalization for stroke immediately following the initiation of typical antipsychotics. Antipsychotics are likely to be initiated after hospitalization for stroke. This practice is likely to reflect the prescribing of antipsychotics during hospital admission for post-stroke complications such as delirium; however, the long-term effects of this practice are unknown. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Up to 21% of adverse drug event related hospital admissions are due to drug interactions. Clinical significance of drug interactions varies. • Studies which only identified drug interactions of potentially major clinical significance found lower prevalence, of between 2 and 16%. • Prevalence of drug interactions defined ‘potentially hazardous’ has had limited study, with no publications identified for the Australian population. WHAT THIS STUDY ADDS • In the study population of 287 074, 1.5% of subjects were dispensed potentially hazardous interacting drug pairs. • However, limited to populations on specific medicines, it was found that for patients dispensed verapamil, methotrexate, amiodarone, lithium, warfarin, cyclosporin and itraconazole, potentially hazardous interactions occurred at a rate greater than 5%. • These patients should be the focus of medication review programmes to avoid potentially serious adverse drug events. BACKGROUND Up to 21% of adverse drug event-related hospital admissions are due to drug interactions. Clinical significance of drug interactions varies, and drug interactions defined ‘potentially hazardous’ are more likely to contribute to morbidity and mortality. AIM The aim of this study was to assess the prevalence of potentially hazardous drug interactions in an elderly Australian veteran population. METHODS This study assessed the prevalence of potentially hazardous drug interactions, where hazardous was defined in three or more international drug interaction references, using Repatriation Pharmaceutical Benefits Scheme pharmacy claims data. Analysis was limited to patients who received regular concurrent dispensings of potentially hazardous interacting medicines. RESULTS Of the 287 074 subjects included in the study, 1.5% were dispensed potentially hazardous interacting drug pairs. For patients dispensed cyclosporin, concomitant use of a statin was common (47%); as was statin use with those dispensed itraconazole (31%). Of those dispensed methotrexate, 24% also received a non-steroidal anti-inflammatory drug; of those on lithium, 18% also received an ACE inhibitor or angiotensin 2 receptor blocker; of those on warfarin, 7.2% and 5.9% were co-dispensed an non-steroidal anti-inflammatory drugs or antiplatelets respectively; for those on verapamil, 5.3% were co-dispensed a beta-blocker, while for those on amiodarone 6.2% were co-dispensed digoxin. CONCLUSIONS Overall prevalence of potentially serious drug interactions appears to be low in the Australian veteran population. However, patients taking cyclosporine, itraconazole, methotrexate, lithium, warfarin, verapamil and amiodarone appear to be most at risk and their medicine use should be regularly reviewed to prevent potentially hazardous drug interactions. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To investigate the prevalence of comorbid conditions in the elderly with diabetes and the prescribing of potentially inappropriate medicines or treatment conflicts. Methods: A cross-sectional study of diabetics aged ≥65 years, using prescription dispensing data from the Australian Department of Veterans’ Affairs. Comorbidities were determined using the comorbidity index Rx-Risk-V. Potentially inappropriate prescribing or treatment conflicts specific for the elderly were determined from guidelines or reference compendia, in addition to the 2003 updated Beers criteria. Results: Of 18,968 diabetics, the median number of comorbidities was 5 (IQR 3–8). Diabetes and associated cardiovascular medicines accounted for 41.9% of all medicine use. Associated cardiovascular diseases were highly prevalent comorbidities. 46% had gastro-oesophageal reflux disease, 25% depression, 20% chronic airways disease or chronic pain and 15% also had heart failure or inflammation-pain. At least 16% were dispensed a medicine associated with adverse effects in patients with diabetes and 22.7% were dispensed at least one potentially inappropriate medicine. Conclusion: Significant comorbid conditions in elderly diabetic patients with potential for inappropriate prescribing or treatment conflicts include arthritis, heart failure, chronic airways diseases and diseases treatable with systemic corticosteroids. Appropriate management of comorbidity should be included in guidelines for the elderly with diabetes. [Copyright &y& Elsevier]

Background: Many observational studies in the general population have demonstrated an increased risk of adverse events associated with NSAIDs, including gastrointestinal bleeds, congestive heart failure, acute renal failure, hypertension and acute myocardial infarction. Few studies, however, have explored outcomes in populations considered to be more vulnerable to their effects. Objective: To determine the rate of adverse events requiring hospitalization that are associated with NSAIDs in two high-risk veteran populations and the general veteran population. Methods: In this retrospective cohort study, we identified veterans being dispensed medicines for diabetes mellitus (diabetes cohort), those receiving renin-angiotensin system medicines and frusemide (furosemide) concurrently (ACE inhibitors/angiotensin II type 1 receptor antagonists [angiotensin receptor blockers; ARBs] and frusemide cohort), or at least one other medicine (general population/reference cohort). The primary endpoint was hospitalization with a primary diagnosis of congestive heart failure, gastrointestinal ulcer, acute renal failure, acute myocardial infarction or hypertension. Hospitalization rates during the period of non-exposure and the 30-day period after a subject was first dispensed an NSAID were compared using Poisson regression. Results: There was a significant increase in risk of all hospitalizations of interest in the exposed period compared with the unexposed period in the diabetes cohort (incidence rate ratio [IRR] 1.31; 95% CI 1.08, 1.60), ACE inhibitor/ARB and frusemide cohort (IRR 1.34; 95% CI 1.13, 1.58) and reference cohort (IRR 1.47; 95% CI 1.30, 1.66). The incidence rates demonstrate that for every 10 000 veterans treated for 30 days with NSAIDs, there were 20 extra hospitalizations in the diabetes population, 30 additional hospitalizations in the ACE inhibitor/ARB and frusemide cohort and 6 extra hospitalizations in the reference population compared with those not treated with NSAIDs. Conclusions: NSAID use is associated with an increased risk of hospitalization in all groups, with similar risk ratio estimates. However, the clinical implications were greater in the high-risk populations, in which more hospitalizations were observed. Consideration may need to be given to differential presentation of risk information to clinicians. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the proportion of veterans with diabetes who had claims for recommended processes of diabetes care in 2005. Design: Observational study of 19,810 veterans’ dispensed medicines indicative of diabetes. Claims to the Department of Veterans’ Affairs for HbA1c, microalbuminuria, ophthalmology or optometry services, podiatry services, diabetes care plans, medication reviews, case conferences and GP management plans were assessed. Results: Overall 63% had at least one HbA1c claim in the year under review, while 40% had a microalbuminuria claim. The majority (87%) had a claim for an ophthalmology or optometry service, while two-thirds had a podiatry service claim. Only one-fifth had claims for an annual diabetes care plan. Just under half had a claim for any type of care plan, including medication review, discharge plan, case conference, GP management plan or health care plan. Veterans resident in aged-care facilities were significantly less likely to have claims for any of these services apart from medication review. Conclusions: While administrative claims data may under-represent some processes of care carried out routinely in general practice, this study suggests under-utilisation of services for veterans with diabetes, particularly those resident in aged-care facilities. [Copyright &y& Elsevier]

Objectives: Pricing polices used in many countries are often viewed in the United States as a mechanism of price constraint. Support for this contention has arisen from pricing studies which demonstrate that the United States pays higher prices for many pharmaceutical products. No study to date, however, has examined the prices paid for pharmaceuticals that provide significant health gain, which might be expected to be lower where price constraints were operating. This study aimed to examine prices paid by federal government programs and agencies in Australia and the United States for pharmaceutical products that provide significant health gain. Methods: Products identified by the US Food and Drug Administration and the Canadian Patented Medicines Prices Review Board as likely to confer significant health gains between 1999 and 2004 were identified. Australian and USfederal government prices ($US) and US average manufacturer prices (AMP), which do not include discounts or rebates, during the second quarter of 2006 were compared. Results: Of 22 products for which comparisons were possible, Australian prices were higher than the US Federal Supply Schedule (FSS) prices for 14 (64%) products. When compared with AMP, Australian prices were higher for eight of the 22 products. Overall, Australian prices were higher on average by 4.2% when compared with the FSS and lower by 14.4% when compared with the AMP. Conclusion: These results suggest that Australian prices for medicines representing significant advances in therapy are similar to those paid under key US programs despite fundamental differences in policy contexts. [ABSTRACT FROM AUTHOR]

What is already known about this subject • Previous cross-sectional studies have demonstrated underuse of cardiovascular medicines in the population with diabetes. What this study adds • Trends are changing over 5 years with increasing use of medicines affecting the angiotensin–renin system, lipid-lowering medicines and antiplatelets in the Australian veteran population, in line with recommended practice. Aim To determine trends over 5 years in cardiovascular medicine use in the Australian veteran population with diabetes Methods An observational study. All veterans dispensed medicines indicative of diabetes between 2000 and 2005 were identified from the Veterans Affairs pharmacy claims dataset. Concurrent dispensings of angiotensin-converting enzyme inhibitor (ACEI), lipid-lowering medicines and antiplatelets were assessed. Results ACEI/angiotensin II receptor blocker use has risen from 46% to 67% in the veteran population dispensed medicines indicative of diabetes. Lipid-lowering medicines have increased from 33% to 58% and antiplatelets from 28% to 50%. Conclusion The increasing use of cardiovascular medicines in the diabetes population is suggestive of improved treatment practices over time, consistent with guidelines and quality use of medicines initiatives. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the prevalence of duplicate antidepressant prescribing and avoidable potential antidepressant drug interactions in the Australian war veteran population. Method: The Department of Veterans' Affairs Pharmacy Claims database was interrogated, using specific criteria, to identify antidepressant duplication. In addition, potential drug interactions where safer alternative therapies were available were assessed. These included anticholinergic agents with tricyclic antidepressants and tramadol with antidepressants. Episodic tramadol dispensings with antidepressants were also assessed. Results: A total of 46 859 veterans had antidepressants regularly dispensed to them in the period 1 April-31 July 2005. Overall, 4037 potential interactions were identified in 3818 veterans (8.1%) to whom were dispensed antidepressants regularly. Antidepressant and tramadol co-prescribing was the most common potential interaction identified among 3.6% of veterans. Two or more interactions were identified in 212 veterans (0.5%). Analysis of episodic tramadol dispensings with antidepressants suggested a much higher prevalence of 7.7%. Conclusion: The increasing use of antidepressants and the high level of potentially avoidable interactions detected in the present study, highlight the necessity of ongoing vigilance concerning the use of potentially inappropriate drug combinations, particularly in the elderly. [ABSTRACT FROM AUTHOR]

Background: It is essential that knowledge gained through health services research is collated and made available for evaluation, for policy purposes and to enable collaboration between people working in similar areas (capacity building). The Australian Quality Use of Medicine (QUM) on-line, web-based project database, known as the QUMmap, was designed to meet these needs for a specific sub-section of health services research related to improving the use of medicines. Australia's National Strategy for Quality Use of Medicines identifies the primacy of consumers as a major principle for quality use of medicines, and aims to support consumer led research. The aim of this study was to determine how consumers as a group have been represented in QUM projects in Australia. A secondary aim was to investigate how the projects with consumer involvement fit into Australia's QUM policy framework. Method: Using the web-based QUMmap, all projects which claimed consumer involvement were identified and stratified into four categories, projects undertaken by; (a) consumers for consumers, (b) health professionals for consumers, (c) health professionals for health professionals, and (d) other. Projects in the first two categories were then classified according to the policy 'building blocks' considered necessary to achieve QUM. Results: Of the 143 'consumer' projects identified, the majority stated to be 'for consumers' were either actually by health professionals for health professionals (c) or by health professionals for consumers (b) (47% and 40% respectively). Only 12 projects (9%) were directly undertaken by consumers or consumer groups for consumers (a). The majority of the health professionals for consumers (b) projects were directed at the provision of services and interventions, but were not focusing on the education, training or skill development of consumers. Conclusion: Health services research relating to QUM is active in Australia and the projects are collated and searchable on the web-based interactive QUMmap. Healthcare professionals appear to be dominating nominally 'consumer focussed' research, with less than half of these projects actively involving the consumers or directly benefiting consumers. The QUMmap provides a valuable tool for policy analysis and for provision of future directions through identification of QUM initiatives. [ABSTRACT FROM AUTHOR]

Medication-related problems are most commonly reported in elderly patients. It is for this reason that the development of services supporting appropriate medication management in the elderly is paramount; particularly for those living in residential care facilities. In 1991, Australia had very limited services supporting the quality use of medicines for residents of aged-care facilities. Over 11 years, from 1991–2002, the range of services has expanded considerably. Federally funded medication review services are now available, with over 80% of residents provided with the service. Medication advisory committees, in accordance with national practice guidelines, have been established in many facilities to address issues concerning medication management. Fifty percent of Australian’s pharmacies are registered to provide services, with over 10% of the country’s pharmacists accredited to provide the service. National practice guidelines for medication management in aged-care facilities have been incorporated into accreditation standards for aged-care facilities, further integrating activity into the wider health system. The environment was created for these activities through the formation of the Pharmaceutical Health and Rational Use of Medicines (PHARM) Committee, an expert advisory committee, and the Australian Pharmaceutical Advisory Council (APAC), a representative council. Both groups had responsibility for advising the Federal Minister of Health. They both identified medication misadventure in residential aged care as a priority issue and through their recommendations the Government devoted funds to the development of best practice guidelines and research activity. Clinical pharmacy services in nursing-home and hostel settings were found to reduce the use of benzodiazepines, laxatives, NSAIDs and antacids leading to cost savings to the health system. Dose-administration aids were found to reduce error rates during medication administration, and the alteration of medications for administration to residents was found to be common practice and potentially problematic. Research in the Australian setting demonstrating effectiveness, as measured by changes in medication use or health outcomes, as well as actual or potential cost savings has been a critical success factor. In addition, prioritisation by government advisory committees, inquiries and policy documents, have assisted in the development of services from ideas in 1991 to nationally funded realities in 2002. [ABSTRACT FROM AUTHOR]

Presents a case study of events which led to changes in the use of the antibiotic, flucloxacillin in Australia. Adverse drug reaction reports; Pharmaceutical industry's advertising of flucloxacillin and cephalexin; Publication reports concerning flucloxacillin and adverse hepatic reactions.

Objectives To measure rates of potentially inappropriate pathology testing in the hospital setting. Methods Retrospective cross-sectional study in hospital setting from July 2021 to December 2021. We examined 3 potentially inappropriate uses: overordering, selection errors, and unnecessary repeat testing. Overordering included vitamin D and lipids (rarely required in acute hospital care). Selection error was the ratio of iron studies to standalone ferritin requests. Unnecessary repeats included any repeat vitamin D, lipids, iron, or ferritin in an episode of care or C-reactive protein (CRP) repeated within 3 days and N-terminal pro–brain natriuretic peptide (NT-proBNP) within 7 days and repeated previously abnormal CRP and NT-proBNP tests. Costs of inappropriate tests were estimated using the Australian Medicare Benefits Schedules. Results Among 55,904 test requests, 15% (n = 8120) were potentially inappropriate. Vitamin D was frequently ordered (n = 4498), as were lipids (n = 2872). Ratio of iron studies to standalone ferritin was 36. Of 19,233 repeat CRPs, 36% (n = 6947) were within 3 days and 62% (n = 179) of repeat NT-proBNPs were within 7 days of the first test. For initially abnormal tests, 89% of CRPs and 97% of NT-proBNPs remained abnormal. Inappropriate test costs accounted for 12% to 30% of costs. Conclusions Frequent potential inappropriate use and selection of pathology tests was observed in South Australian hospitals. [ABSTRACT FROM AUTHOR]

The author reflects on the challenges in assessing and improving medication safety across the whole health system and the lack of comprehensive audits of medication safety errors where medication errors across all aspects of hospital care are measured. He cites the need for carers and patients to be active participants in improving medication safety as more people living with multiple chronic illness are taking multiple medicines and being treated by multiple providers.

The author explores the clinical and pharmacovigilance challenges involving multidrug interactions. She mentions the challenge posed by the growing prevalence of people with multiple chronic health conditions and taking multiple medications, the importance of systems pharmacology in predicting multidrug interactions and the need to direct attention on the prevention of potential interactions to reduce possible multidrug interactions.

This study aimed to identify opportunities for clinical decision support targeting medication safety in remote primary care, by investigating the relationship between clinical workflows, health system priorities, cognitive tasks, and reasoning processes in the context of medicines used in people with chronic kidney disease (CKD).This qualitative study involved one-on-one, semistructured interviews. The participants were healthcare professionals employed in a clinical or managerial capacity with clinical work experience in a remote health setting for at least 1 year.Twenty-five clinicians were interviewed. Of these, four were rural medical practitioners, nine were remote area nurses, eight were Aboriginal health practitioners, and four were pharmacists. Four major themes were identified from the interviews: (1) the need for a clinical decision support system to support a sustainable remote health workforce, as clinicians were “constantly stretched” and problems may “fall through the cracks”; (2) reliance on digital health technologies, as medical staff are often not physically available and clinicians-on-duty usually “flick an email and give a call so that I can actually talk it through to our GP”; (3) knowledge gaps, as “it takes a lot of mental space” to know each patient's renal function and their medication history, and clinicians believe “mistakes can be made”; and (4) multiple risk factors impacting CKD management, including clinical, social and behavioural determinants.The high prevalence of CKD and reliance on digital health systems in remote primary health settings can make a clinical decision support system valuable for supporting clinicians who may not have extensive experience in managing medicines for people with CKD. [ABSTRACT FROM AUTHOR]

Background: Frailty and medicine‐related problems are common among the elderly and have been associated with an increased risk of adverse outcomes. However, there has been limited research on the association between frailty and medicines use. Aim: To determine the distribution of frailty among older people who used medicines and to examine the difference in frailty scores over time with continuation or discontinuation of specific medicines. Methods: The study population was from the Australian Longitudinal Study of Ageing (ALSA). The data used in the analysis were collected in 1992 (wave 1) and in 1995 (wave 3). Frailty scores were assessed at both waves using a modified version of the Frailty Index. Non‐parametric tests were used to examine the difference in the distribution of frailty scores in relation to medicines used at baseline. Medicine use was categorised into continued or stopped by comparing use at wave 3 to use at baseline. A t‐test was used to compare the mean changes in frailty scores between the two groups, with a p‐value of <0.05 considered to be significant. Results: Data from 2087 participants were included. At baseline, a higher number of medicines used was associated with higher frailty scores (p < 0.0001). Stopping any preventive medicines, as well as beta‐blockers, or potassium‐sparing diuretics, was associated with a higher increase in mean frailty score changes than continuing these medicines, p = 0.01, p = 0.03 and p = 0.004, respectively. Conclusions: There was an association between frailty and medicines use. Further study is needed to assess whether the progression of frailty was due to medicine cessation or vice versa. [ABSTRACT FROM AUTHOR]

• The effects of medicines on physical function have not been quantified. • We studied the association between medicine changes and 24-hour activity composition. • As sedative/anticholinergic load increased, sedentary time increased. • Wearable accelerometry bands can be used to monitor the effects of medicines on physical function. Studies have shown that use of medicines with sedative or anticholinergic properties is associated with a decline in physical function; however, the effects have not been quantified, and it is not known how and which specific physical movements are affected. This prospective study quantified the impact of a change in sedative or anticholinergic load over time on 24-hour activity composition. This study used data collected from a randomised trial assessing an ongoing pharmacist service in residential aged care. The 24-hour activity composition of sleep, sedentary behaviour, light-intensity physical activity, and moderate to vigorous physical activity was derived from 24-hour accelerometry bands. Mixed effect linear models were used to regress the multivariate outcome of 24-hour activity composition on medication load at baseline and at 12 months. A fixed effect interaction between trial stage and medication load was included to test for differing sedative or anticholinergic load effects at the two trial stages. Data for 183 and 85 participants were available at baseline and 12 months respectively. There was a statistically significant interaction between medication load and time point on the multivariate outcome of 24-hour activity composition (sedative F = 7.2, p < 0.001 and anticholinergic F = 3.2, p = 0.02). A sedative load increase from 2 to 4 over the 12-month period was associated with an average increase in daily sedentary behaviour by an estimated 24 min. As sedative or anticholinergic load increased, there was an increase in sedentary time. Our findings suggest wearable accelerometry bands are a possible tool for monitoring the effects on physical function of sedative and anticholinergic medicines. The ReMInDAR trial was registered on the Australian and New Zealand Trials Registry ACTRN12618000766213. [ABSTRACT FROM AUTHOR]

Background: Aged care residents are vulnerable to the harmful effects of medicines; however, data on the prevalence and preventability of adverse medicine events in aged care residents are scarce. Aim: To determine the prevalence and preventability of adverse medicine events in Australian aged care residents. Methods: A secondary analysis of data from the Reducing Medicine-Induced Deterioration and Adverse Reactions (ReMInDAR) trial was conducted. Potential adverse medicine events were identified and independently screened by two research pharmacists to produce a short-list of potential adverse medicine events. An expert clinical panel reviewed each potential adverse medicine to determine the likelihood that the event was medicine related (based on the Naranjo Probability Scale criteria). The clinical panel assessed preventability of medicine-related events using Schumock-Thornton criteria. Results: There were 583 adverse events due to medicines, involving 154 residents (62% of the 248 study participants). There was a median of three medication-related adverse events (interquartile range [IQR] 1–5) per resident over the 12-month follow-up period. The most common medication-related adverse events were falls (56%), bleeding (18%) and bruising (9%). There were 482 (83%) medication-related adverse events that were preventable, most commonly falls (66% of preventable adverse medicine events), bleeding (12%) and dizziness (8%). Of the 248 residents, 133 (54% of the cohort) had at least one preventable adverse medicine event, with a median of 2 (IQR 1–4) preventable adverse medicine events per resident. Conclusion: In total, 62% of aged care residents in our study had an adverse medicine event and 54% had a preventable adverse medicine event in a 12-month period. [ABSTRACT FROM AUTHOR]

Purpose: Many studies of persistence involving fixed dose combinations (FDCs) of cardiovascular medicines have not adequately accounted for a user's prior experience with similar medicines. The aim of this research was to assess the effect of prior medicine experience on persistence to combination therapy. Patients and methods: Two retrospective cohort studies were conducted in the complete Pharmaceutical Benefits Scheme prescription claims dataset. Initiation and cessation rates were determined for combinations of: ezetimibe/statin; and amlodipine/statin. Initiators to combinations of these medicines between April and September 2013 were classified according to prescriptions dispensed in the prior 12 months as either: experienced to statin or calcium channel blocker (CCB); or naïve to both classes of medicines. Cohorts were stratified according to formulation initiated: FDC or separate pill combinations (SPC). Cessation of therapy over 12 months was determined using Kaplan–Meier survival analysis. Risk of cessation, adjusted for differences in patient characteristics was assessed using Cox proportional hazard models. Results: There were 12,169 people who initiated combinations of ezetimibe/statin; and 26,848 initiated combinations of amlodipine/statin. A significant proportion of each cohort were naïve initiators: ezetimibe/statin cohort, 1,964 (16.1%) of whom 81.9% initiated a FDC; and amlodipine/statin cohort, 5,022 (18.7%) of whom 55.4% initiated a FDC. Naïve initiators had a significantly higher risk of ceasing therapy than experienced initiators regardless of formulation initiated: ezetimibe/statin cohort, naïve FDC versus experienced FDC HR=3.0 (95% CI 2.8, 3.3) and naïve SPC versus experienced SPC HR=4.4 (95% CI 3.8, 5.2); and amlodipine/statin cohort naïve FDC versus experienced FDC HR=2.0 (95% CI 1.8, 2.2) and naïve SPC versus experienced SPC HR=1.5 (95% CI 1.4,1.6). Conclusion: Prescribers are initiating people to combinations of two cardiovascular medicines without prior experience to at least one medicine in the combination. This is associated with a higher risk of ceasing therapy than when combination therapy is initiated following experience with one component medicine. The use of FDC products does not overcome this risk. [ABSTRACT FROM AUTHOR]

Aim: To compare persistence in people who initiate the combination of amlodipine and statin as a fixed-dose combination (FDC) or separate pill combination (SePC), and assess the impact of prior medicine exposure on this outcome.Method: Prescription dispensing data from a national administrative dataset was used to identify patients initiating FDCs or SePCs of amlodipine and statin between April and September 2013. Each cohort was stratified according to dispensing of calcium channel blockers (CCBs) or statins in the prior 12 months. Time to cessation of combination therapy (persistence) was analyzed over 12 months using Kaplan Meyer survival analysis and Cox proportional hazards (PH) models. Patient factors associated with length of treatment were identified using Cox PH modeling.Results: Of 26,000 people who initiated combination amlodipine and statin, the majority initiated SePCs (77%). The unadjusted cessation rates at 12 months were SePC 40% and FDC 44%. Following adjustment for patient factors, the risk of ceasing combination therapy was higher in those taking the SePC versus FDC, hazard ratio (95% CI): 1.15 (1.11, 1.21). Patients naïve to both therapies had double the cessation rate compared to those who had at least one prior dispensing of a statin. Factors positively associated with persistence were prior use of other antihypertensive drugs and reaching the medicine subsidy safety-net: factors that were more common in users of SePC amlodipine and statin.Conclusion: In this study we found a lower risk (15%) of ceasing combination therapy when people initiate amlodipine and statin in the form of a FDC. While this outcome supports findings in other countries that FDCs improve persistence with combination therapy, prior experience with component or similar medicines has a larger impact on persistence regardless of formulation initiated. [ABSTRACT FROM AUTHOR]

Background: Objective measures for screening, prioritizing, and planning care for frail individuals are essential for appropriate aged care provision. This study evaluates metrics derived from actigraphy measures (captured by wrist accelerometer) as a digital biomarker to identify frail individuals at risk of adverse outcomes, including death, hospitalization, and cognitive decline. Methods: This was a secondary study using data from a randomized controlled trial assessing the effectiveness of an ongoing pharmacist service in residential aged care facilities. Three metrics are studied and compared: the Frailty Index, the daily time spent in light time activity, and the temporal correlation of the actigraphy signal, measured by detrended fluctuation analysis. The association between actigraphy‐derived metrics at baseline and adverse events within 12 months (death, cognitive decline, and hospitalizations) was assessed using logistic regression. Results: Actigraphy records were available for 213 participants living in aged‐care, median age of 85 years. Individuals with higher temporal correlation (activity is less random) were at lower risk of death (Standardized OR: 0.49; 95% CI 0.34, 0.7, p < 0.001) and hospitalization (Standardized OR: 0.57; 95% CI 0.42, 0.77, p < 0.001) in 12 months, but there was no difference in cognitive decline (Standardized OR: 1; 95% CI 0.74, 1.35, p = 0.98). The predictive model that included temporal correlation had an area under the curve of 0.70 (CI 0.60–0.80) for death and 0.64 (CI 0.54–0.72) for hospitalization. Conclusion: Temporal correlation of the actigraphy signal from aged care residents was strongly associated with death and hospitalization, but not cognitive decline. Digital biomarkers may have a place as an objective, accurate, and low‐cost patient metric to support risk stratification and clinical planning. [ABSTRACT FROM AUTHOR]

Objectives: This paper aimed to review and synthesise the qualitative research evidence on the experiences and perceptions of dementia in Vietnam and among the Vietnamese diaspora. Methods: Systematic searches were conducted in June 2019 using Medline, Embase, Emcare, PsycINFO and Cochrane electronic databases, as well as grey literature. Keywords and Medical Subject Headings [MeSH terms] for dementia and associated terms were combined with keywords for Vietnam and its provinces. Qualitative research articles published in English or Vietnamese were included to examine evidence on the life experiences of Vietnamese people with dementia using thematic analysis. Results: Our searches resulted in 3,940 papers, from which 21 qualitative research studies were included for final analysis. The majority of research has not been undertaken in Vietnam but with the Vietnamese diaspora in Western countries and has taken a cultural perspective to analyses. Research in Western countries has focused on the need for culturally adapted and culturally sensitive models of care. Emerging themes about the life experiences of Vietnamese people with dementia identified from the studies included: many people do not have diagnostic terms for dementia but use the descriptive language of symptoms; stigma was a reported problem and on occasions can be observed in the descriptive language used for people with dementia; cultural and traditional values create both an opportunity and a barrier, supporting compassion, family care and relaxation, but creating barriers to accessing health services or long-term residential care. Conclusions: This is the first systematic review reporting qualitative evidence on the life experiences of people with dementia in Vietnam and among the Vietnamese diaspora. Future research is needed on the voice of people with dementia themselves and their caregivers particularly in Vietnam, and low and middle-income countries with regards to living with dementia, pathways to care from diagnosis, treatment, care and support, additional social care and preparedness for end of life care for people with dementia. [ABSTRACT FROM AUTHOR]

Background: The Australian Government Department of Veterans' Affairs (DVA) funds an ongoing health promotion based program to improve use of medicines and related health services, which implements interventions that include audit and feedback in the form of patient-specific feedback generated from administrative claims records. We aimed to determine changes in medicine use as a result of the program.Methods: The program provides targeted patient-specific feedback to medical practitioners. The feedback is supported with educational material developed by a clinical panel, subject to peer review and overseen by a national editorial committee. Veterans who meet target criteria also receive educational brochures. The program is supported by a national call centre and ongoing national consultation. Segmented regression analyses (interrupted time series) were undertaken to assess changes in medication use in targeted veterans pre and post each intervention.Results: 12 interventions were included; three to increase medicine use, seven which aimed to reduce use, and two which had combination of messages to change use. All programs that aimed to increase medicine use were effective, with relative effect sizes at the time of the intervention ranging from 1% to 8%. Mixed results were seen with programs aiming to reduce inappropriate medicine use. Highly specific programs were effective, with relative effect sizes at the time of the intervention of 10% decline in use of NSAIDs in high risk groups and 14% decline in use of antipsychotics in dementia. Interventions targeting combinations of medicines, including medicine interactions and potentially inappropriate medicines in the elderly did not change practice significantly. Interventions with combinations of messages targeting multiple components of practice had an impact on one component, but not all components targeted.Conclusions: The Veterans' MATES program showed positive practice change over time, with interventions increasing use of appropriate medicines where under-use was evident and reduced use of inappropriate medicines when single medicines were targeted. Combinations of messages were less effective, suggesting specific messages focusing on single medicines are required to maximise effect. The program provides a model that could be replicated in other settings. [ABSTRACT FROM AUTHOR]

Objective. To compare the demographic, socioeconomic, and medical characteristics of patients who had a General Practitioner Management Plan (GPMP) with those for patients without GPMP. Methods. Cohort study of patients with chronic diseases during the time period 1 July 2006 to 30 June 2008 using the Australian Department of Veterans' Affairs (DVA) claims database. Results. Of the 88 128 veterans with chronic diseases included in the study, 23 015 (26%) veterans had a GPMP and 11 089 (13%) had a Team Care Arrangement (TCA). Those with a GPMP had a higher number of comorbidities (P < 0.001), and a higher use of services such as health assessment and medicine review (P < 0.001) than did those without GPMP. Diabetes was associated with a significantly increased use of GPMP compared with all other chronic diseases except heart failure. Conclusions. GPMPs are used in a minority of patients with chronic diseases. Use is highest in people with diabetes. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to compare adherence and persistence in patients who add ezetimibe to statin therapy as a separate pill combination (SPC) or fixed dose combination (FDC). Method This is a retrospective cohort study of prescription data conducted in an Australian health dataset. Two cohorts were identified: those dispensed statins and subsequently ezetimibe as either SPC or FDC. We compared adherence to combination therapy using the medication possession ratio (MPR), multivariate linear and logistic regression. Persistence to initial combination medicines and any lipid-lowering therapies were analysed using Kaplan Meyer survival and Cox proportional hazards models. Results A total of 3651 people initiated ezetimibe SPC and 5740 ezetimibe FDC. There was no significant difference in adherence with mean MPRs: ezetimibe SPC = 0.99 (95% confidence interval 0.98-1.01) and FDC = 0.97 (95% CI 0.95-0.99). One year persistence rates to initial combination medicines were ezetimibe SPC 49.1% vs. FDC 62.4%; hazard ratio (HR) = 1.81 (95% CI 1.76-1.90). However, persistence to any lipid-lowering therapy was higher in those initiating ezetimibe SPC = 84.9% vs. FDC = 76%; HR = 0.62 (95% CI 0.55-0.72). One year persistence rates to any two lipid-lowering medicines were similar: ezetimibe SPC 65.2% and FDC 65%. Conclusion In this study FDCs have little impact on either adherence or persistence to combination lipid-lowering therapy in people who have been taking statins. The benefit of higher persistence to FDCs in first episode of treatment with initial medicines is debatable as persistence to dual therapy was similar in both cohorts. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics are frequently and increasingly prescribed to treat the behavioural symptoms associated with dementia despite their modest efficacy. Evidence regarding the potential adverse events of antipsychotics is limited and little is known about the longer-term safety of these medicines in the elderly. The aim of this review was to determine the impact of the choice of observational study design and methods used to control for confounding on the measurement of antipsychotic risks in elderly patients.Methods: We searched PUBMED and the Cochrane controlled trials register for double-blind randomised controlled trials (RCTs), meta-analyses and published observational studies of antipsychotics.Results: Forty four studies were identified for the endpoints; death, cerebrovascular events, hip fracture and pneumonia. RCTs found a 20% to 30% increased risk of death, or an absolute increase of 1extra death per 100 patients with atypical antipsychotics compared to non-use. Cohort and instrumental variable analyses estimated between 2 to 7 extra deaths per 100 patients with conventional compared to atypical antipsychotics. RCTs found a 2 to 3 times increased risk of all cerebrovascular events with atypical antipsychotics compared to placebo and no association with serious stroke that required hospitalisation. Observational studies using cohort and self-controlled case-series designs reported similar results; no association where the endpoint was stroke causing hospitalisation and a doubling of risk when minor stroke was included. No RCTs were available for the outcome of hip fracture or pneumonia. Observational studies reported a 20% to 40% increased risk of hip fracture with both antipsychotic classes compared to non-use. The risk of pneumonia was a 2 to 3 times greater with both classes compared to non-use while a self-controlled case-series study estimated a 60% increased risk. Conventional antipsychotics were associated with a 50% greater hip fracture risk than atypical antipsychotics, while the risk of pneumonia was similar between the classes.Conclusions: Choice of observational study design is critical in studying the adverse effects of antispychotics. Cohort and instrumental variable analyses gave more consistent results to clinical studies for mortality outcomes as have self-controlled case-series for the risk of cerebrovascular events and stroke. Observational evidence has highlighted the potential for antipsychotics to be associated with serious adverse events that were not reported in RCTs including hip fracture and pneumonia. Good quality observational studies are required, that employ appropriate study designs that are robust towards unmeasured confounding, to confirm the potential excess risk of hip fracture and pneumonia with antipsychotics. [ABSTRACT FROM AUTHOR]

Background: Pain is an indication for total hip arthroplasty (THA) and it should be resolved post-surgery. Because patients' pain is typically treated pharmacologically we tested whether opioid use can be used as a surrogate for patient-reported pain and as an indicator for early surgical failure. Specifically, we evaluated whether the amount of opioids taken within the year after THA was associated with one and five years risk of revision surgery.Methods: A cohort of 9943 THAs (01/2001-12/2012) was evaluated. Post-operative opioid use was the exposure of interest and cumulative daily oral morphine equivalent (OME) amounts were calculated. Total OMEs/90-day periods were categorised into quartiles. Revisions within one and five years were the outcomes of interest.Results: Of the THAs, 2.0 % (N = 200) were revised within one year and 4.2 % (N = 413) within five years. After adjustments for gender, age, surgical indication, co-morbidities, and other analgesics, revision was associated with amount of OMEs in the second quarter after THA (days 91-180 after discharge). Patients on medium-high amounts of OME (400-1119 mg) had higher risk of one (hazard ratio (HR) = 2.22, 95 % CI 1.08-4.56) and five year (HR = 1.66, 95 % CI 1.08-2.56) revision than a patient not taking opioids. During the same period, patients taking the highest amounts of OMEs (≥1120 mg) had a 2.64 (95 % CI 1.03-6.74) times higher risk of one year and a 2.11 (95 % CI 1.13-3.96) times higher risk of five year revision.Conclusions: Opioid use 91-180 days post-surgery is associated with higher risk of revision surgery and therefore is an early and useful indicator for surgical failure. [ABSTRACT FROM AUTHOR]

Background: Joint arthroplasty patients have a high prevalence of co-morbidities and this impacts their surgical outcomes. There are different ways to ascertain co-morbidities and appropriate measurement is necessary. The purpose of this study was to: (1) describe the prevalence of co-morbidities in a cohort of total hip arthroplasty (THA) and knee arthroplasty (TKA) patients using two diagnoses-based measures (Charlson and Elixhauser) and one prescription-based measure (RxRisk-V); (2) compare the agreement of co-morbidities amongst the measures.Methods: A cross-sectional study of Australian veterans undergoing THAs (n = 11,848) and TKAs (n = 18,972) between 2001 and 2012 was conducted. Seventeen co-morbidities were identified using the Charlson, 30 using the Elixhauser, and 42 using the RxRisk-V measure. Agreement between co-morbidities was calculated using Kappa (κ) statistics.Results: Combining measures, 64 conditions were identified, of these 28 were only identified using the RxRisk-V, 11 using the Elixhauser, and 2 using the Charlson. The most prevalent conditions was pain treated with anti-inflammatories (58.7% THAs, 55.9% TKAs), pain treated with narcotics (55.0% THAs, 50.9% TKAs), hypertension (56.0% THAs and TKAs), and anticoagulation disorders (53.0% THAs, 48.6% TKAs). Diabetes was the only condition with substantial agreement (all κ > 0.6) amongst all measures. When comparing the diagnoses based algorithms, agreement was high for overlapping conditions (all κ > 0.71).Conclusions: Different measures identified different co-morbidities, provided different estimates for the same co-morbidity, and had different levels of agreement for common co-morbidities. This highlights the importance of understanding co-morbidity measures and using them appropriately in studies and case-mix adjustments analyses. [ABSTRACT FROM AUTHOR]

Randomized controlled trials always report the dose assessed and usually include a measure of adherence. By comparison, observational studies assessing medication safety often fail to report the dose used and rarely report any measure of adherence to therapy. This limits the ability to control for differences in doses used when undertaking meta-analyses. Non-adherence with therapy is common in the practice setting and varies across countries and settings. Inter-country differences in the registration of medicines may also result in different product strengths being available in different countries. These two factors combined means that observational studies undertaken for the same medicine in different settings may be assessing the same medicine but in circumstances where quite different dosages are used. Given that many adverse drug effects are dose dependent, differences in dosages used could be a factor explaining differences in risk estimates observed across studies. We argue that dose intensity, which can be defined as a product of the dose prescribed and adherence to the dose prescribed over the course of treatment, should be routinely reported in observational studies of medication safety. We illustrate the issue with the example of dabigatran. The randomized controlled trial evidence underpinning dabigatran's marketing authorization resulted in uncertainty about the appropriate dose for efficacy versus safety. As a result, different dosages of dabigatran were registered in the USA and Europe. The USA registered the 150- and 75-mg dabigatran products, while the 150- and 110-mg dabigatran products were registered in Europe. Among five observational studies subsequently undertaken to resolve the safety question concerning dabigatran and risk of bleeding, only one stratified results by dose. None of the US studies stratified results by the 75-mg dabigatran dose, despite this dose not being assessed in the original trial. None of the five studies reported adherence measures, despite three separate observational studies finding between 25 and 40 % of patients were non-adherent to dabigatran. The STROBE and RECORD statements should consider adding the requirement for reporting measures of dose intensity and its component products to improve observational study reports. [ABSTRACT FROM AUTHOR]

Introduction: Regulatory advisories on hydroxyzine and risk of QT prolongation and Torsade de pointes (TdP) were issued in the UK in April 2015 and Canada in June 2016. We hypothesized patients with risk factors for QT prolongation and TdP, compared with those without risk factors, would be less likely to initiate hydroxyzine in the UK and in British Columbia (BC), Canada, following advisories. Methods: We conducted a longitudinal study with repeated measures, and evaluated hydroxyzine initiation in a UK cohort and a concurrent BC control cohort (April 2013–March 2016) as well as in a BC advisory cohort (June 2014–May 2017). Results: This study included 247,665 patients in the UK cohort, 297,147 patients in the BC control cohort, and 303,653 patients in the BC advisory cohort. Over a 12-month post-advisory period, hydroxyzine initiation decreased by 21% in the UK (rate ratio 0.79, 95% confidence interval 0.66–0.96) relative to the expected level of initiation based on the pre-advisory trend. Hydroxyzine initiation did not change in the BC control cohort or following the Canadian advisory in the BC advisory cohort. The decrease in hydroxyzine initiation in the UK in the 12 months after the advisories was not significantly different for patients with risk factors compared with those without risk factors. Conclusion: Hydroxyzine initiation decreased in the UK, but not in BC, in the 12 months following safety advisories. The decrease in hydroxyzine initiation in the UK was not significantly different for patients with versus without risk factors for QT prolongation and TdP. [ABSTRACT FROM AUTHOR]

Background: In elderly populations, paracetamol may be used regularly for conditions such as osteoarthritis. Paracetamol has been associated with respiratory disease through a proposed mechanism of glutathione depletion and oxidative stress. Given that chronic obstructive pulmonary disease (COPD) is frequently co-morbid with osteoarthritis, this study investigated whether the dose and timing of paracetamol exposure may induce COPD exacerbations.Methods: The study population was 3523 Australian Government Department of Veterans' Affairs full entitlement holders who had existing COPD on 1 January 2011, who were dispensed at least one prescription of paracetamol between 1 January 2011 and 30 September 2015, and had no paracetamol dispensed in the 6 months prior to 1 January 2011. The outcome was time to first hospitalisation for COPD exacerbation after initiation of paracetamol. A weighted cumulative exposure approach was used.Results: The association between paracetamol exposure and COPD exacerbation was protective or harmful depending on the dose, duration, and recency of exposure. Compared to non-use, current use at the maximum dose of 4 g daily for 7 days was associated with a lower risk (HR = 0.78, 95% CI = 0.67-0.92) and a higher risk after 30 days (HR = 1.27, 95% CI = 1.06-1.52). Risk declined to baseline after 2 months. For past use, there was a short-term increase in risk on discontinuation depending of dose, duration and time since stopping.Conclusions: Patients and doctors should be aware of the possible risk of COPD exacerbation with higher dose paracetamol 1 to 6 weeks after initiation or discontinuation, but no increased risk after 2 months. [ABSTRACT FROM AUTHOR]

Background: The use of cardiac implantable electronic devices (CIED), which includes pacemakers, implantable cardioverter-defibrillators (ICD), cardiac resynchronisation therapy pacemakers (CRT-P) and cardiac resynchronisation therapy defibrillators (CRT-D) has increased over the past 20 years, but there is a lack of real world evidence on the longevity of these devices in the older population which is essential to inform health care delivery and support clinical decisions.Methods and Results: We conducted a retrospective cohort study using data from the Australian Government Department of Veterans' Affairs database. The cohort consisted of people who had a CIED procedure between 2005 and 2015. The cumulative risk of generator replacement/reoperations was estimated accounting for the competing risk of death. A total of 16,662 patients were included. In pacemaker recipients with an average age of 85 years, the 5-year risk of reoperation ranged from 2.8% in single chamber, 3.6% in dual chamber to 7.6% in CRT-P recipients, while the 5-year risk of dying with the index pacemaker in situ was 63% in single chamber, 46% in dual chamber and 56% in CRT-P recipients. In defibrillator recipients with an average age of 80 years, the 5-year risk of reoperation ranged from 11% in single chamber, 13% in dual chamber to 24% in CRT-D recipients, while the 5-year risk of dying with the index defibrillator in situ was 46% in single chamber, 40% in dual chamber and 41% in CRT-D recipients.Conclusion: In this cohort of older patients the 5-year risk of generator reoperation was low in pacemaker recipients whereas up to one in four CRT-D recipients would have a reoperation within 5 years. [ABSTRACT FROM AUTHOR]

Introduction: Medication-related problems often lead to patient harm. This paper aims to review the Australian literature to determine the overall incidence, severity and preventability of medication-related hospital admissions, as well as providing a national estimate on their extent and cost. Methods: The first part of the paper includes a literature search to identify studies that provided estimates of medication-related problems that caused hospital admissions. Incidence of medication-related hospital admissions, type of medication-related problem contributing to admission (e.g. adverse medicine reaction) and method used to estimate incidence (e.g. chart review) were extracted. Data on severity and preventability of the admissions were extracted where available. The second part of the paper involves use of methodological triangulation to estimate the extent and cost of medication-related hospital admission. Median estimates used to assess medication-related hospital admissions and the 2019–2020 national hospital admissions data were used to calculate the national estimate on the extent of medication-related hospital admission. Costs were also estimated. Results: Seventeen studies provided estimates on the extent of medication-related hospital admissions as assessed using medication chart review. The median incidence of 2.5% (interquartile range [IQR] 0.6%) as a proportion of all hospital admissions suggests 275,000 hospital admissions annually in Australia are medication related. The median incidence of 9% (IQR 3.9%) of emergency admissions suggests that 270,000 admissions annually are medication related. Eight studies provided estimates of the extent of medication-related hospital admissions identified from administrative health data; the median incidence of 1.7% with an under-reporting rate of 82% suggests 280,000 hospital admissions annually are medication related. Triangulation of results suggests that at least 250,000 hospital admissions annually in Australia are medication related, with an estimated cost of 1.4 billion Australian dollars (AUD$). Five studies assessed severity, and nine studies assessed preventability. Preventability estimates suggest two-thirds of medication-related hospital admissions are potentially preventable. Conclusions: We estimated that 250,000 hospital admissions in Australia are medication related, with an annual cost of AUD$1.4 billion to the healthcare system. Two-thirds of medication-related hospital admissions are potentially preventable. [ABSTRACT FROM AUTHOR]

Background: Hip fracture impacts on quality of life and may lead to premature death. In Australia, the extent of use of medicines that increase risk of falls or hip fracture in at-risk older people is not known. Aim: To determine the use of medicines associated with falls or hip fracture before hip fracture and whether medicine use changed after hip fracture. Method: Data from the Australian Department of Veterans' Affairs healthcare claims database were used. The cohort included patients aged > 65 years who were hospitalised for hip fracture in 2009. Percentages of patients using medicines associated with falls or hip fracture were calculated in the 6 weeks before hospitalisation for hip fracture. McNemar's test was used to assess changes in medicines used before admission and after discharge from hospital. Results: 2235 patients with a median age of 87 years had hip fractures in 2009. At least 1 medicine that increases risk of falls or hip fracture was used by 84% of patients before admission. Of the drug classes that increase risk of falls or hip fracture, the 4 most commonly dispensed before admission were antihypertensives (63%), antidepressants (29%), benzodiazepines (26%) and opioids (19%). After discharge, the use of antipsychotics (p < 0.0001), opioids (p < 0.0001), benzodiazepines (p = 0.0009) and antidepressants (p = 0.01) increased significantly. Conclusion: Most older patients used at least 1 medicine that increases the risk of falls or hip fracture before and after hip fracture. Antipsychotic, opioid, benzodiazepine and antidepressant use increased significantly after hospital discharge. [ABSTRACT FROM AUTHOR]

It is known that younger patients treated with antipsychotics are at increased risk of metabolic events; however, it is unknown how this risk varies according to ethnicity, the class of antipsychotic and the specific product used, and by age group. We conducted a multinational sequence symmetry study in Asian populations (Hong Kong, Japan, Korea, Taiwan and Thailand) and non-Asian populations (Australia and Denmark) to evaluate the metabolic events associated with antipsychotics in both Asian and non-Asian populations, for typical and atypical antipsychotics, and by the subgroups of children and adolescents, and young adults. Patients aged 6–30 years newly initiating oral antipsychotic drugs were included. We defined a composite outcome for metabolic events which included dyslipidemia, hypertension and hyperglycemia. We calculated the sequence ratio (SR) by dividing the number of people for whom a medicine for one of the outcome events was initiated within a 12-month period after antipsychotic initiation by the number before antipsychotic initiation. This study included 346,904 antipsychotic initiators across seven countries. Antipsychotic use was associated with an increased risk of composite metabolic events with a pooled adjusted SR (ASR) of 1.22 (95% CI 1.00–1.50). Pooled ASRs were similar between Asian (ASR, 1.22; 95% CI 0.88–1.70) and non-Asian populations (ASR, 1.22; 95% CI 1.04–1.43). The pooled ASR for typical and atypical antipsychotics was 0.98 (95% CI 0.85–1.12) and 1.24 (95% CI 0.97–1.59), respectively. No difference was observed in the relative effect in children and adolescents compared to young adults. The risk of metabolic events associated with antipsychotics use was similar in magnitude in Asian and non-Asian populations despite the marked difference in drug utilization patterns. [ABSTRACT FROM AUTHOR]