Reducing opioid use for chronic non-cancer pain in primary care using an evidence-based, theory-informed, multistrategic, multistakeholder approach: a single-arm time series with segmented regression.

BACKGROUND: Many countries have high opioid use among people with chronic non-cancer pain. Knowledge about effective interventions that could be implemented at scale is limited. We designed a national intervention that included audit and feedback, deprescribing guidance, information on catastrophising assessment, pain neuroscience education and a cognitive tool for use by patients with their healthcare providers. METHOD: We used a single-arm time series with segmented regression to assess rates of people using opioids before (January 2015 to September 2017), at the time of (October 2017) and after the intervention (November 2017 to August 2019). We used a cohort with historical comparison group and log binomial regression to examine the rate of psychologist claims in opioid users not using psychologist services prior to the intervention. RESULTS: 13 968 patients using opioids, 8568 general practitioners, 8370 pharmacies and accredited pharmacists and 689 psychologists were targeted. The estimated difference in opioid use was -0.51 persons per 1000 persons per month (95% CI -0.69, -0.34; p<0.001) as a result of the intervention, equating to 25 387 (95% CI 24 676, 26 131) patient-months of opioid use avoided during the 22-month follow-up. The targeted group had a significantly higher rate of incident patient psychologist claims compared with the historical comparison group (rate ratio: 1.37, 95% CI 1.16, 1.63; p<0.001), equating to an additional 690 (95% CI 289, 1167) patient-months of psychologist treatment during the 22-month follow-up. CONCLUSIONS: Our intervention addressed the cognitive, affective and sensory factors that contribute to pain and consequent opioid use, demonstrating it could be implemented at scale and was associated with a reduction in opioid use and increasing utilisation of psychologist services.

The association between exacerbation of chronic obstructive pulmonary disease and timing of paracetamol use: a cohort study in elderly Australians.

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.

Implementation and Evaluation of a Digitally Enabled Precision Public Health Intervention to Reduce Inappropriate Gabapentinoid Prescription: Cluster Randomized Controlled Trial.

BACKGROUND: Digital technologies can enable rapid targeted delivery of audit and feedback interventions at scale. Few studies have evaluated how mode of delivery affects clinical professional behavior change and none have assessed the feasibility of such an initiative at a national scale. OBJECTIVE: The aim of this study was to develop and evaluate the effect of audit and feedback by digital versus postal (letter) mode of delivery on primary care physician behavior. METHODS: This study was developed as part of the Veterans' Medicines Advice and Therapeutics Education Services (MATES) program, an intervention funded by the Australian Government Department of Veterans' Affairs that provides targeted education and patient-specific audit with feedback to Australian general practitioners, as well as educational material to veterans and other health professionals. We performed a cluster randomized controlled trial of a multifaceted intervention to reduce inappropriate gabapentinoid prescription, comparing digital and postal mode of delivery. All veteran patients targeted also received an educational intervention (postal delivery). Efficacy was measured using a linear mixed-effects model as the average number of gabapentinoid prescriptions standardized by defined daily dose (individual level), and number of veterans visiting a psychologist in the 6 and 12 months following the intervention. RESULTS: The trial involved 2552 general practitioners in Australia and took place in March 2020. Both intervention groups had a significant reduction in total gabapentinoid prescription by the end of the study period (digital: mean reduction of 11.2%, P=.004; postal: mean reduction of 11.2%, P=.001). We found no difference between digital and postal mode of delivery in reduction of gabapentinoid prescriptions at 12 months (digital: -0.058, postal: -0.058, P=.98). Digital delivery increased initiations to psychologists at 12 months (digital: 3.8%, postal: 2.0%, P=.02). CONCLUSIONS: Our digitally delivered professional behavior change intervention was feasible, had comparable effectiveness to the postal intervention with regard to changes in medicine use, and had increased effectiveness with regard to referrals to a psychologist. Given the logistical benefits of digital delivery in nationwide programs, the results encourage exploration of this mode in future interventions.

Evaluation of Renal Function Testing in Older Australian Veterans Dispensed Medicines that Require Renal Function Monitoring.

INTRODUCTION: Renal function testing should be performed prior to initiating medicines that require dose adjustment in renal impairment, with ongoing monitoring in continued use, particularly in older people. There is little evidence regarding the extent to which renal function monitoring is performed in older Australians dispensed medicines requiring renal function monitoring. OBJECTIVE: The aim of this study was to determine the extent of renal function testing in older people dispensed medicines requiring renal function monitoring. METHODS: A retrospective analysis of administrative claims data from the Australian Government Department of Veterans' Affairs was conducted for people aged 65 years or older who were dispensed one or more medicines requiring renal function monitoring, from 1 June 2019 to 30 September 2019, to investigate the proportion of people with a claim for a pathology test that included creatinine levels in the 6-12 months before or after dispensing of a medicine requiring renal function monitoring. RESULTS: There were 100,113 people who were dispensed at least one medicine requiring renal function monitoring during the study period, of whom 15% had a history of renal impairment and 16% had diabetes mellitus. Sixty-one percent had a claim for a test in the prior 6 months; this increased to 80% of participants with a claim for a test in the prior 12 months. The rate of claims for testing was lower in aged care facility residents compared with people living in the community (54% vs 62% in the previous 6 months; p < 0.001), and was higher in people with diabetes (75% vs 58%; p < 0.001), history of renal impairment (91% vs 59%; p < 0.001) or heart failure (77% vs 60%; p < 0.001) compared with those without these conditions. CONCLUSION: Medicines that require renal function monitoring are commonly used in older Australians, and while the majority have claims for tests that include renal function, some are missing out.

Medication-related hospital admissions in aged care residents.

OBJECTIVE: To determine the prevalence of medication-related hospitalisations preceded by potentially suboptimal processes of care in aged care residents. METHOD: We conducted a retrospective analysis of administrative claims data from the Australian Government Department of Veterans' Affairs (DVA). We identified all hospital admissions for aged care residents between 1 July 2014 and 30 June 2019. The proportion of hospital admissions preceded by potentially suboptimal medication-related processes of care was determined. RESULTS: A total of 18 874 hospitalisations were included, and 46% were preceded by potentially suboptimal medication-related care. One-quarter of fracture admissions occurred in residents at risk of fracture who were not using a medicine to prevent fracture, and 87% occurred in residents using falls-risk medicines. Thirty per cent of heart failure admissions occurred in patients who were not using an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. CONCLUSION: Nearly half of hospital admissions were preceded by potentially suboptimal medication-related processes of care. Interventions to improve use of medicines for aged care residents in these areas are warranted.

Comorbidities in an Australian sample of chronic and new opioid users.

INTRODUCTION AND AIMS: Mental health disorders and substance abuse are risk factors that both precede and follow chronic opioid use. We predicted that incident opioid users would have lower rates of mental health comorbidities than chronic opioid users, but that incident chronic opioid users would have lower rates of mental health comorbidities than prevalent chronic users. DESIGN AND METHODS: We used administrative health claims data to evaluate differences in lifetime mental health and substance abuse comorbidity profiles of people who were prevalent and incident chronic opioid users, as well as those who used opioids acutely. Results were stratified by age. RESULTS: Over 5,188 people were prevalent chronic opioid users at study entry. Of the 10,079 people who initiated opioids, 10.2 per-cent had a subsequent chronic episode (incident chronic) and the remainder stopped within 90 days (incident acute). In prevalent chronic users compared to incident chronic users, rates of depression and anxiety were higher across all age groups (odds ratio (OR) across age groups range from = 1.60, 95 percent confidence interval (CI) = 1.35,1.89, to OR = 6.66, 95 percent CI = 3.02, 14.69) and prevalence of alcohol abuse was higher in those aged 55 to 74 years (OR = 5.11, 95 percent CI = 1.83, 14.24, p = 0.002). Acute users were less likely than incident chronic users to have depression and anxiety in those aged over 74 years (depression OR = 0.82, 95 per-cent CI = 0.70, 0.95; anxiety OR = 0.82, 95% CI 0.70, 0.98). CONCLUSIONS: Mental health morbidities commonly associated with chronic opioid use increase in prevalence as chronic use continues.

Comparative effectiveness and safety of low-strength and high-strength direct oral anticoagulants compared with warfarin: a sequential cohort study.

OBJECTIVES: The aim of this study was to compare effectiveness and safety of low-strength and high-strength direct oral anticoagulants (DOACs) with warfarin in the Australian Veteran population. DESIGN: Sequential cohort study using inverse probability of treatment weighting (IPTW) and propensity score matching. Initiators of high-strength (apixaban 5 mg, dabigatran 150 mg, rivaroxaban 20 mg) and low-strength DOACS (apixaban 2.5 mg, dabigatran 110 mg, rivaroxaban 15 mg) were compared with warfarin initiators. SETTING: Australian Government Department of Veterans' Affairs claims database. PARTICIPANTS: 4836 patients who initiated oral anticoagulants (45.8%, 26.0% and 28.2% on low-strength, high-strength DOACs and warfarin, respectively) between August 2013 and March 2015. Mean age was 85, 75 and 83 years for low-strength, high-strength DOACs and warfarin initiators, respectively. MAIN OUTCOME MEASURES: One-year risk of hospitalisation for ischaemic stroke, any bleeding event or haemorrhagic stroke. Secondary outcomes were 1-year risk of hospitalisation for myocardial infarction and death. RESULTS: Using the IPTW method, no difference in risk of ischaemic stroke or bleeding was found with low-strength DOACs compared with warfarin. As a class, no increased risk of myocardial infarction was found for low-strength DOACs, however, risk was elevated for apixaban (HR 2.25, 95% CI 1.23 to 4.13). For high-strength DOACs, no difference was found for ischaemic stroke compared with warfarin, however, there was a significant reduction in risk of bleeding events (HR 0.63, 95% CI 0.44 to 0.89) and death (HR 0.40, 95% CI 0.28 to 0.58). Propensity score matching showed no difference in risk of ischaemic stroke or bleeding. CONCLUSION: We found that in the practice setting both DOAC formulations were similar to warfarin with regard to effectiveness and had no increased risk of bleeding.

Persistence with opioids post discharge from hospitalisation for surgery in Australian adults: a retrospective cohort study.

OBJECTIVE: To determine time to opioid cessation post discharge from hospital in persons who had been admitted to hospital for a surgical procedure and were previously naïve to opioids. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study using administrative health claims database from the Australian Government Department of Veterans' Affairs (DVA). DVA gold card holders aged between 18 and 100 years who were admitted to hospital for a surgical admission between 1 January 2014 and 30 December 2015 and naïve to opioid therapy prior to admission were included in the study. Gold card holders are eligible for all health services that DVA funds. MAIN OUTCOME MEASURES: The outcome of interest was time to cessation of opioids, with follow-up occurring over 12 months. Cessation was defined as a period without an opioid prescription that was equivalent to three times the estimated supply duration. The proportion who became chronic opioid users was defined as those who continued taking opioids for greater than 90 days post discharge. Cumulative incidence function with death as a competing event was used to determine time to cessation of opioids post discharge. RESULTS: In 2014-2015, 24 854 persons were admitted for a surgical admission. In total 3907 (15.7%) were discharged on opioids. In total 3.9% of those discharged on opioids became chronic users of opioids. The opioid that the patients were most frequently discharged with was oxycodone; oxycodone alone accounted for 43%, while oxycodone with naloxone accounted for 8%. CONCLUSIONS: Opioid initiation post-surgical hospital admission leads to chronic use of opioids in a small percentage of the population. However, given the frequency at which surgical procedures occur, this means that a large number of people in the population may be affected. Post-discharge assessment and follow-up of at-risk patients is important, particularly where psychosocial elements such as anxiety and catastrophising are identified.

Using Post-market Utilisation Analysis to Support Medicines Pricing Policy: An Australian Case Study of Aflibercept and Ranibizumab Use.

OBJECTIVES: To describe how post-market utilisation analysis in Australia informs cost-effectiveness assessment and pricing decisions, using aflibercept and ranibizumab as case studies. METHODS: Pharmaceutical claims were used to identify initiators of aflibercept and ranibizumab in the year after aflibercept-listing (December 2012), and ranibizumab initiators in the year before aflibercept listing. The dispensing rates for each cohort were calculated, and their demographic and clinical characteristics compared using Kruskal-Wallis tests. RESULTS: Aflibercept and ranibizumab each accounted for half the age-related macular degeneration market following aflibercept listing. Aflibercept initiators had similar dispensing rates to ranibizumab initiators in the pre- and post-aflibercept era (~ three scripts during the first 90 days, and eight to nine scripts during the following 12 months). All cohorts were similar in terms of their age, sex, residential aged-care status and geographic remoteness, and no differences were observed in their overall co-morbidity scores and history of thromboembolic events. CONCLUSIONS: Contrary to clinical trial protocols, post-market utilisation research for ranibizumab and aflibercept demonstrates equivalent use in practice in terms of dose frequency, and the demographic and clinical characteristics of initiators. This supports Australia's decision to pay the same price for each rather than giving a premium to aflibercept. Many other countries are likely overpaying for aflibercept if their utilization patterns are similar to Australia's, and could benefit from incorporating routine utilisation assessment.

Reducing hypnotic use in insomnia management among Australian veterans: results from repeated national interventions.

BACKGROUND: The Australian Government Department of Veterans' Affairs (DVA) Veterans' Medicines Advice and Therapeutics Education Services (Veterans' MATES) programme conducted two intervention (March 2009, follow-up intervention June 2012) both of which aimed to reduce hypnotic use among Australian veterans. We evaluated the effectiveness of the interventions, and estimated the associated health consequences. METHODS: Both interventions targeted veterans who had been dispensed hypnotics prior to the intervention. Patient-specific prescriber feedback containing patient details and the volume of hypnotics dispensed, along with tailored educational information, was mailed to general practitioners. Veterans, pharmacists and directors of care in residential aged care facilities were mailed tailored educational information. Interrupted time-series and segmented regression modelling were used to determine the effect of the two interventions on the rate of hypnotics dispensing. The cumulative patient-months of hypnotic treatment avoided as a result of the interventions was calculated. We estimated improvements in health consequences of as a result of hypnotic treatment avoided based on the results of cohort studies in the same population identifying the association between hypnotic and sedative use on the outcomes of falls, and confusion. RESULTS: After the first Veterans' MATES intervention in March 2009, hypnotic use declined by 0.2% each month, when compared to the baseline level (p = 0.006). The intervention effect was attenuated after one year, and use of hypnotics was found to increase by 0.2% per month after March 2010. Following the second intervention in June 2012, there was a further significant decline in use of 0.18% each month over the 12 months of follow up (p = 0.049). The cumulative effect of both interventions resulted in 20,850 fewer patient-months of treatment with hypnotics. This cumulative reduction in hypnotic use was estimated to lead to a minimum of 1 fewer hospital admissions for acute confusion and 7 fewer hospital admissions due to falls. CONCLUSIONS: The Veterans' MATES insomnia interventions which involved multiple stakeholders were effective in reducing hypnotic use among older Australians. Repetition of key messages led to sustained practice change.

The validity of the Rx-Risk Comorbidity Index using medicines mapped to the Anatomical Therapeutic Chemical (ATC) Classification System.

OBJECTIVES: To provide a map of Anatomical Therapeutic Chemical (ATC) Classification System codes to individual Rx-Risk comorbidities and to validate the Rx-Risk Comorbidity Index. DESIGN: The 46 comorbidities in the Rx-Risk Index were mapped to dispensing's indicative of each condition using ATC codes. Prescription dispensing claims in 2014 were used to calculate the Rx-Risk. A baseline logistic regression model was fitted using age and gender as covariates. Rx-Risk was added to the base model as an (1) unweighted score, (2) weighted score and as (3) individual comorbidity categories indicating the presence or absence of each condition. The Akaike information criterion and c-statistic were used to compare the models. SETTING: Models were developed in the Australian Government Department of Veterans' Affairs health claims data, and external validation was undertaken in a 10% sample of the Australian Pharmaceutical Benefits Scheme Data. PARTICIPANTS: Subjects aged 65 years or older. OUTCOME MEASURES: Death within 1 year (eg, 2015). RESULTS: Compared with the base model (c-statistic 0.738, 95% CI 0.734 to 0.742), including Rx-Risk improved prediction of mortality; unweighted score 0.751, 95% CI 0.747 to 0.754, weighted score 0.786, 95% CI 0.782 to 0.789 and individual comorbidities 0.791, 95% CI 0.788 to 0.795. External validation confirmed the utility of the weighted index (c-statistic=0.833). CONCLUSIONS: The updated Rx-Risk Comorbidity Score was predictive of 1-year mortality and may be useful in practice to adjust for confounding in observational studies using medication claims data.

Posttraumatic Stress Disorder, Antipsychotic Use and Risk of Dementia in Veterans.

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.

Use of proton pump inhibitors among older Australians: national quality improvement programmes have led to sustained practice change.

OBJECTIVE: To evaluate the impact of national multifaceted initiatives to improve use of proton pump inhibitors (PPIs) on the use of PPIs among older Australians. DESIGN: Interrupted time series analysis using administrative health claims data from the Australian Government Department of Veterans' Affairs (DVA). SETTING: Australia. PARTICIPANTS: All veterans and dependents who received PPIs between January 2003 and December 2013. INTERVENTION(S): National, multifaceted interventions to improve PPI use were conducted by the Australian Government Department of Veterans' Affairs Veterans' MATES programme and Australia's NPS MedicineWise in April 2004, June 2006, May 2009 and August 2012. MAIN OUTCOME MEASURE(S): Trends in monthly rate of use of any PPI among the veteran population, and the monthly rate of use of low strength PPIs among all veterans dispensed a PPI. RESULTS: Interventions in 2004, 2006, 2009 and 2012 slowed the rate of increase in PPI use significantly, with the 2012 intervention resulting in a sustained 0.04% decrease in PPI use each month. The combined effect of all four interventions was a 20.9% (95% CI 7.8-33.9%) relative decrease in PPI use 12 months after the final intervention. The four interventions also resulted in a 42.2% (95% CI 19.9-64.5%) relative increase in low strength PPI use 12 months after the final intervention. CONCLUSIONS: National multifaceted programmes targeting clinicians and consumers were effective in reducing overall PPI use and increasing use of low strength PPIs. Interventions to improve PPI use should incorporate regular repetition of key messages to sustain practice change.

Central Nervous System-Acting Medicines and Risk of Hospital Admission for Confusion, Delirium, or Dementia.

BACKGROUND: Most studies assessing the effect of central nervous system (CNS)-acting medicines on cognitive disturbances have focused on the use of individual medicines. The impact on cognitive function when another CNS-acting medicine is added to a patient's treatment regimen is not well known. OBJECTIVE: To determine risk of hospitalization for confusion, delirium, or dementia in older people associated with increasing numbers of CNS-acting medicines taken concurrently, as well as the number of standard doses taken each day (measured as defined daily doses). DESIGN: Retrospective cohort study, from July 2011 to June 2012, using health claims data. SETTING: Australian veteran population. PARTICIPANTS: A total of 74,321 community-dwelling individuals aged 65 years and over, who were dispensed at least 1 CNS-acting medicine in the year before study entry. Patients with prior hospitalization for confusion or delirium, and those with dementia or receiving palliative care, were excluded. MAIN OUTCOME MEASURE: Hospitalization for confusion, delirium, or dementia. RESULTS: Over the 1-year study period, 401 participants were hospitalized with confusion, delirium, or dementia. Adjusted analyses showed the risk of hospitalization was 2.4 times greater with the use of 2 CNS-acting medicines compared with no use [incident rate ratio (IRR) 2.39, 95% confidence interval (CI) 1.79-3.19, P < .001], and more than 19 times greater when 5 or more CNS-acting medicines were taken concurrently (IRR 19.35, 95% CI 11.10-33.72, P < .001). Similarly, the risk of hospitalization was significantly increased among patients taking between 1.0 and 1.9 standard doses per day (IRR 2.64, 95% CI 1.99-3.50, P < .001) and between 2.0 and 2.9 standard doses per day (IRR 3.43, 95% CI 2.07-5.69, P < .001) compared with no use. CONCLUSIONS: Use of multiple CNS-acting medicines or higher doses is associated with an increased risk of hospitalization for confusion, delirium, or dementia. Health care professionals need to be alert to the contribution of CNS-acting medicines among patients presenting with confusion or delirium and consider strategies to reduce treatment burden where possible.

Commitment questions targeting patients promotes uptake of under-used health services: Findings from a national quality improvement program in Australia.

RATIONALE: Interventions asking patients to commit to speaking with their doctor about a health-related issue could be used to improve quality of care. OBJECTIVE: To evaluate the impact of commitment questions targeting patients on the uptake of recommended health services within a national quality improvement program (Veterans' MATES). METHODS: Patients targeted in the home medicines reviews (HMRs), dose administration aids (DAAs), renal function testing and diabetes interventions were posted educational information and response forms which asked whether they intended to talk to their general practitioner (GP) about the targeted service. Uptake of the service after each intervention was determined using health claims data. Log binomial regression models compared the monthly rate of service use in the nine months post-intervention among patients answering 'yes' to a commitment question with non-responders and patients answering 'no' or 'unsure'. RESULTS: Each intervention targeted up to 58,000 patients. The average response rate was 28%. Positive responses were associated with increased uptake of HMRs (rate ratio (RR) 2.64, 95% CI 2.39-2.92; p < 0.0001), dose administration aids (RR 2.53, 95% CI 2.29-2.79; p < 0.0001), renal function tests (RR 1.18, 95% CI 1.13-1.24; p < 0.0001), GP management plans (RR 1.30, 95% CI 1.14-1.48; p < 0.0001) and diabetes care plans (RR 1.47, 95% CI 1.24-1.75; p < 0.0001) compared to non-responders. Similar increases in uptake were also observed among positive responders when compared to patients responding 'no' or 'unsure' to the commitment question. CONCLUSION: Positive responses to commitment questions distributed as part of national, multifaceted interventions were consistently associated with increased uptake of targeted services.

Association between Ophthalmic Timolol and Hospitalisation for Bradycardia.

Introduction. Ophthalmic timolol, a topical nonselective beta-blocker, has the potential to be absorbed systemically which may cause adverse cardiovascular effects. This study was conducted to determine whether initiation of ophthalmic timolol was associated with an increased risk of hospitalisation for bradycardia. Materials and Methods. A self-controlled case-series study was undertaken in patients who were hospitalised for bradycardia and were exposed to timolol. Person-time after timolol initiation was partitioned into risk periods: 1-30 days, 31-180 days, and >180 days. A 30-day risk period prior to initiating timolol was also included. All remaining time was considered unexposed. Results. There were 6,373 patients with at least one hospitalisation for bradycardia during the study period; 267 were exposed to timolol. Risk of bradycardia was significantly increased in the 31-180 days after timolol initiation (incidence rate ratio (IRR) = 1.93; 95% confidence interval (CI) 1.00-1.87). No increased risk was observed in the first 30 days or beyond 180 days of continuous exposure (IRR = 1.40; 95% CI 0.87-2.26 and IRR = 1.21; 95% CI 0.64-2.31, resp.). Conclusion. Bradycardia is a potential adverse event following timolol initiation. Practitioners should consider patient history before choosing a glaucoma regime and closely monitor patients after treatment initiation with topical nonselective beta-blocker eye drops.

Multiple anticholinergic medication use and risk of hospital admission for confusion or dementia.

OBJECTIVES: To identify the association between use of multiple anticholinergic medications and risk of hospitalization for confusion or dementia. DESIGN: Retrospective cohort study conducted over 2 years between July 2010 and June 2012, using administrative claims data from the Australian Department of Veterans' Affairs. SETTING: Australia. PARTICIPANTS: Australian veterans dispensed at least one moderately or highly anticholinergic medication in the year before study start. MEASUREMENTS: Cumulative anticholinergic use on each day of the study period was determined. The association between hospitalization for confusion or dementia and number of anticholinergic medications used at the time of admission was compared against times during which participants were not taking anticholinergic medications. Sensitivity analyses were undertaken limiting the outcome to admissions for acute confusion and excluding individuals taking antipsychotics. RESULTS: Adjusted results showed a significantly greater risk of hospitalization for confusion or dementia when individuals were taking two or more anticholinergic medications. The adjusted incident rate ratios (IRRs) were 2.58 (95% confidence interval (CI) = 1.91-3.48) for those taking two anticholinergics and 3.87 (95% CI = 1.83-8.21) for those taking three or more. Sensitivity analyses in which participants taking antipsychotic medications were excluded and the outcome was limited to acute confusion also found similar risks for those taking two (IRR 1.82, 95% CI = 1.18-2.80) and three or more (IRR = 3.98 95% CI = 1.50-10.58) anticholinergic medications. CONCLUSION: Taking more anticholinergic medications is associated with greater risk of hospitalization for confusion or dementia. Strategies to reduce anticholinergic medication burden are likely to translate into significant health benefits.

Ranibizumab and risk of hospitalisation for ischaemic stroke and myocardial infarction in patients with age-related macular degeneration: a self-controlled case-series analysis.

BACKGROUND: Ranibizumab, a vascular endothelial growth factor (VEGF) inhibitor, is used in the treatment of age-related macular degeneration. Inhibition of VEGF has an anti-angiogenic action and is associated with thrombogenicity, thus, myocardial infarction and ischaemic stroke are potential side effects of VEGF inhibitors. OBJECTIVE: Our objective was to assess the association between use of ranibizumab and risk of hospitalisation for ischaemic stroke (IS) and myocardial infarction (MI). METHODS: The self-controlled case series design was used, including subjects exposed to ranibizumab (Anatomical Therapeutic Chemical [ATC] code S01LA04) who were hospitalized for IS (International Classification of Diseases, tenth edition [ICD-10] code I63) or the combined endpoint of stroke or transient ischaemic attack (TIA) (ICD-10 code G45) or MI (ICD-10 code I21) were identified between August 2007 and March 2013. Rate ratios in exposed periods compared with unexposed periods were calculated using conditional Poisson regression. RESULTS: A total of 323 subjects received ranibizumab and were hospitalized for IS, 490 for IS or TIA, and 391 for MI. Median period of exposure was 8-9 months with follow-up times of approximately 2.8 years. No elevated risk of IS was seen in the 1-30 days post initiation (incidence rate ratio [IRR] 1.36; 95% confidence interval [CI] 0.98-1.88); however, elevated risk was observed for those who received therapy for 31-60 days (IRR 1.91; 95% CI 1.13-3.24). Sensitivity analyses adjusting for time-varying confounders found elevated risk in both the 1-30 days and 31-60 days periods. Similar results to those for IS were observed for the combined endpoint of IS or TIA. No association was seen for MI in either time period (1-30 days IRR 0.90, 95% CI 0.65-1.23; 31-60 days IRR 0.98, 95% CI 0.54-1.79). CONCLUSION: This case-series analysis suggests an increased risk of hospitalisation for ischaemic stroke for patients receiving ranibizumab in the 31-60 days risk period. Studies with larger populations are required to confirm the risk in the 1-30 days risk period. No evidence of increased risk of hospitalisation for MI was observed.