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.

Influence of drug safety advisories on drug utilisation: an international interrupted time series and meta-analysis.

OBJECTIVE: To evaluate the association between regulatory drug safety advisories and changes in drug utilisation. DESIGN: We conducted controlled, interrupted times series analyses with administrative prescription claims data to estimate changes in drug utilisation following advisories. We used random-effects meta-analysis with inverse-variance weighting to estimate the average postadvisory change in drug utilisation across advisories. STUDY POPULATION: We included advisories issued in Canada, Denmark, the UK and the USA during 2009-2015, mainly concerning drugs in common use in primary care. We excluded advisories related to over-the-counter drugs, drug-drug interactions, vaccines, drugs used primarily in hospital and advisories with co-interventions within ±6 months. MAIN OUTCOME MEASURES: Change in drug utilisation, defined as actual versus predicted percentage change in the number of prescriptions (for advisories without dose-related advice), or in the number of defined daily doses (for dose-related advisories), per 100 000 population. RESULTS: Among advisories without dose-related advice (n=20), the average change in drug utilisation was -5.83% (95% CI -10.93 to -0.73; p=0.03). Advisories with dose-related advice (n=4) were not associated with a statistically significant change in drug utilisation (-1.93%; 95% CI -17.10 to 13.23; p=0.80). In a post hoc subgroup analysis of advisories without dose-related advice, we observed no statistically significant difference between the change in drug utilisation following advisories with explicit prescribing advice, such as a recommendation to consider the risk of a drug when prescribing, and the change in drug utilisation following advisories without such advice. CONCLUSIONS: Among safety advisories issued on a wide range of drugs during 2009-2015 in 4 countries (Canada, Denmark, the UK and the USA), the association of advisories with changes in drug utilisation was variable, and the average association was modest.

Variation in health service use by veterans with an accepted disability of post-traumatic stress disorder who had a service record post 1975: a cluster analysis.

BACKGROUND: The use of health services is likely to vary among veterans with an accepted disability of post-traumatic stress disorder (PTSD), however, the extent of variation is not known. We aimed to determine the extent and type of health services used by veterans with an accepted disability of PTSD. METHODS: The cohort included veterans who served post 1975, were eligible for all Australian Government Department of Veterans' Affairs funded health services, had PTSD as an accepted disability prior to July 2015 and were alive at the 30 June 2016. Veterans were assigned to groups based on their use of health services using K-means cluster analysis. RESULTS: The cohort comprised five clusters involving 2286 veterans. The largest cluster (43%) were a younger, general practitioner (GP) managed cluster who saw their GP quarterly and the psychiatrist twice a year. The second GP cluster (30%) had higher levels of physical comorbidity. The psychiatrist managed cluster (14%) had a mean of 12 psychiatrist visits and one PTSD hospitalisation in the year. The remaining two clusters involved GP and allied healthcare, but no psychologist care. High levels of antidepressant use occurred in all clusters, ranging from 44% up to 69%. The psychiatrist managed cluster had 47% on antipsychotics and 58% on anxiolytics. CONCLUSION: Our study highlights the heterogeneity in health service use. These results identify the significant health utilisation required for up to one-sixth of veterans with PTSD and the significant role of primary care physicians in supporting veterans with PTSD.

Impact of a patient-specific national programme aimed at increasing the use of emollient moisturisers to reduce the risk of skin tears: a longitudinal cohort study.

OBJECTIVES: To evaluate the impact of a patient-specific national programme targeting older Australians and health professionals that aimed to increase use of emollient moisturisers to reduce to the risk of skin tears. DESIGN: A prospective cohort intervention. PARTICIPANTS: The intervention targeted 52 778 Australian Government's Department of Veterans' Affairs patients aged over 64 years who had risk factors for wound development, and their general practitioners (GPs) (n=14 178). OUTCOME MEASURES: An interrupted time series model compared the rate of dispensing of emollients in the targeted cohort before and up to 23 months after the intervention. Commitment questions were included in self-report forms. RESULTS: In the first month after the intervention, the rate of claims increased 6.3-fold (95% CI: 5.2 to 7.6, p<0.001) to 10 emollient dispensings per 1000 patients in the first month after the intervention. Overall, the intervention resulted in 10 905 additional patient-months of treatment. The increased rate of dispensing among patients who committed to talking to their GP about using an emollient was six times higher (rate ratio: 6.2, 95% CI: 4.4 to 8.7) than comparison groups. CONCLUSIONS: The intervention had a sustained effect over 23 months. Veterans who responded positively to commitment questions had higher uptake of emollients than those who did not.

Reducing medicine-induced deterioration and adverse reactions (ReMInDAR) trial: study protocol for a randomised controlled trial in residential aged-care facilities assessing frailty as the primary outcome.

INTRODUCTION: Many medicines have adverse effects which are difficult to detect and frequently go unrecognised. Pharmacist monitoring of changes in signs and symptoms of these adverse effects, which we describe as medicine-induced deterioration, may reduce the risk of developing frailty. The aim of this trial is to determine the effectiveness of a 12-month pharmacist service compared with usual care in reducing medicine-induced deterioration, frailty and adverse reactions in older people living in aged-care facilities in Australia. METHODS AND ANALYSIS: The reducing medicine-induced deterioration and adverse reactions trial is a multicentre, open-label randomised controlled trial. Participants will be recruited from 39 facilities in South Australia and Tasmania. Residents will be included if they are using four or more medicines at the time of recruitment, or taking more than one medicine with anticholinergic or sedative properties. The intervention group will receive a pharmacist assessment which occurs every 8 weeks. The pharmacists will liaise with the participants' general practitioners when medicine-induced deterioration is evident or adverse events are considered serious. The primary outcome is a reduction in medicine-induced deterioration from baseline to 6 and 12 months, as measured by change in frailty index. The secondary outcomes are changes in cognition scores, 24-hour movement behaviour, grip strength, weight, percentage robust, pre-frail and frail classification, rate of adverse medicine events, health-related quality of life and health resource use. The statistical analysis will use mixed-models adjusted for baseline to account for repeated outcome measures. A health economic evaluation will be conducted following trial completion using data collected during the trial. ETHICS AND DISSEMINATION: Ethics approvals have been obtained from the Human Research Ethics Committee of University of South Australia (ID:0000036440) and University of Tasmania (ID:H0017022). A copy of the final report will be provided to the Australian Government Department of Health. TRIAL REGISTRATION NUMBER: Australian and New Zealand Trials Registry ACTRN12618000766213.

Analysis of anticholinergic and sedative medicine effects on physical function, cognitive function, appetite and frailty: a cross-sectional study in Australia.

OBJECTIVE: To test the association between use of medicines with anticholinergic or sedative properties and physical function, cognitive function, appetite and frailty. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study analysed baseline data collected as part of the Australian Longitudinal Study of Ageing, a population-based cohort of 2087 participants aged 65 years or over living in South Australia. MAIN OUTCOME MEASURES: Physical function was measured at baseline using measures including hand grip strength, walking speed, chair stands, activities of daily living and instrumental activities of daily living (IADL). Cognitive function was measured using Mini-Mental State Examination. Appetite was measured using Center for Epidemiologic Studies Depression question 2. Frailty was measured using frailty index. The association between use of anticholinergics or sedatives and physical or cognitive function, appetite, or frailty was assessed using analysis of covariance and ordinal or binary logistic regression. RESULTS: Almost half of the population were using anticholinergics or sedatives (n=954, 45.7%). Use of anticholinergics was significantly associated with poorer grip strength, slower walking speed, poorer IADL and poorer appetite. Use of sedatives was significantly associated with poorer grip strength, slower walking speed and poorer IADL. We found no significant association between medicine use and cognitive function. Users of anticholinergics or sedatives were significantly more likely to be frail compared with non-users. CONCLUSION: Use of medicines with anticholinergic or sedative properties is significantly associated with poorer physical function, poorer appetite and increased frailty. Early identification of signs and symptoms of deterioration associated with medicine use is particularly important in older people so that worsening frailty and subsequent adverse events are prevented.

Sequence symmetry analysis graphic adjustment for prescribing trends.

BACKGROUND: Sequence symmetry analysis (SSA) is a signal detection method that can be used to assist with adverse drug event detection. It provides both a risk estimate and a data visualisation. Published methods provide results in the form of an adjusted sequence ratio, which adjusts for underlying market trends of medicine use, however no method for adjusting the visualisation is available. We aimed to develop and evaluate another method of adjustment for prescribing trends and apply it to the SSA visualisation. METHODS: The SSA method relies on incident prescriptions for pairs of medicines of interest. Smoothing curves were fitted to the frequency distributions of incident medicine use. When divided and normalised, these curves yielded a set of proportions related to differences in prescribing trends over follow-up. These were then used to adjust the unit counts for incident prescriptions in the SAA visualisation and to calculate the sequence ratio. Curve fitting was also used to identify the proportional relationship between sequences over time for SSA and is presented as a supplementary visualisation to the SSA. We compared the sensitivity and specificity of our method with that from the SSA method of Tsiropolous et al. RESULTS: Curve-fit adjusted SSA visualisations yielded adjusted sequence ratios very close to those of Tsiropolous, with a p-value of 0.999 for the two sample Kolmogorov-Smirnov test. Results for sensitivity and specificity derived from adjusted sequence ratios were also practically the same. The curve-fit method graphically indicates the proportionality of the sequence and provides a useful supplement of net differences between the two sides of the SSA visualisation. Additionally, we found that incident prescriptions for patients common to both distributions are best precluded from adjustment calculations, leaving only incident prescriptions for patients unique to one or other distribution. This improved the accuracy of SSA in some atypical instances with negligible affect on accuracy elsewhere. CONCLUSIONS: Our curve-fit method is equivalent to current methods in the literature for adjusting prescribing trends in SAA, with the advantage of providing adjustment incorporated in the SAA visualisation.

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.

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.

Inflated medicine prices in Vietnam: a qualitative study.

One third of the world's population lacks regular access to essential medicines partly because of the high cost of medicines. In Vietnam, the cost to patients of medicines was 47 times the international reference price for originator brands and 11 times the price for generic equivalents in the public sector. In this article, we report the results of a qualitative study conducted to identify the principal reasons for inflated medicine prices in Vietnam.Between April 2008 and December 2009, 29 semi-structured interviews were conducted with staff from pharmaceutical companies, private pharmacies, the Ministry of Health, and the Ministry of Finance of Vietnam. Study participants were recruited using a combination of purposive and snowball sampling techniques. Interviews were recorded, transcribed and coded using NVivo8® software and analyzed using a framework of structure-conduct-performance (SCP).Participants attributed high prices of originator medicines to a monopoly of supply. The prices of generic medicines were also considered to be excessive, reportedly due to the need to recoup the cost of financial inducements paid to prescribers and procurement officers. These inducements constituted a dominant cost component of the end price of generic medicines. Poor market intelligence about current world prices, as well as failure to achieve economies of scale because of unwarranted duplication in pharmaceutical production and distribution system were also factors contributing to high prices. This was reported to be further compounded by multiple layers in the supply chain and unregulated retail mark-ups.To address these problems a multifaceted approach is needed encompassing policy and legislative responses. Policy options include establishing effective monitoring of medicine quality assurance, procurement, distribution and use. Rationalization of the domestic pharmaceutical production and distribution system to achieve economies of scale is also required. Appropriate legal responses include collaborations with the justice and law enforcement sectors to enforce existing laws.

Policy options for pharmaceutical pricing and purchasing: issues for low- and middle-income countries.

Pharmaceutical expenditure is rising globally. Most high-income countries have exercised pricing or purchasing strategies to address this pressure. Low- and middle-income countries (LMICs), however, usually have less regulated pharmaceutical markets and often lack feasible pricing or purchasing strategies, notwithstanding their wish to effectively manage medicine budgets. In high-income countries, most medicines payments are made by the state or health insurance institutions. In LMICs, most pharmaceutical expenditure is out-of-pocket which creates a different dynamic for policy enforcement. The paucity of rigorous studies on the effectiveness of pharmaceutical pricing and purchasing strategies makes it especially difficult for policy makers in LMICs to decide on a course of action. This article reviews published articles on pharmaceutical pricing and purchasing policies. Many policy options for medicine pricing and purchasing have been found to work but they also have attendant risks. No one option is decisively preferred; rather a mix of options may be required based on country-specific context. Empirical studies in LMICs are lacking. However, risks from any one policy option can reasonably be argued to be greater in LMICs which often lack strong legal systems, purchasing and state institutions to underpin the healthcare system. Key factors are identified to assist LMICs improve their medicine pricing and purchasing systems.

Comorbidity of chronic disease and potential treatment conflicts in older people dispensed antidepressants.

OBJECTIVES: the study aimed to examine the prevalence of comorbidity, the prescribing of potentially inappropriate medications and treatment conflicts in a large sample of older people who have been dispensed an antidepressant medicine. METHODS: a cross-sectional study of administrative claims data from the Department of Veterans' Affairs, Australia, 1 April-31 July 2007, of veterans aged > or =65 years was conducted. Comorbidities determined using the pharmaceutical-based comorbidity index, Rx-Risk-V. Concomitant medicines that may be potentially inappropriate for patients with depression and areas of treatment conflicts were determined from Australian clinical guidelines or reference compendia. RESULTS: a total of 39,695 subjects were included, with a median of 5 comorbid conditions (inter-quartile range 3-6). Ninety percent of medicine use was attributed to the treatment of comorbid conditions. Eighty-seven percent of the study cohort was identified as having at least one comorbid condition that may cause a potential treatment conflict when an antidepressant is used. Those conditions of most concern included cardiovascular diseases, anxiety disorders, arthritis or pain management and osteoporosis. CONCLUSION: we observed a high level of potentially inappropriate prescribing and treatment conflicts that may arise when caring for older patients dispensed an antidepressant with comorbidity. These have the potential to place a large number of older people with depression at increased risk for adverse events.

Medicines information in medical journal advertising in Australia, Malaysia and the United States: A comparative cross-sectional study.

OBJECTIVE: The aim of this study was to compare the provision of medicines information in medical journal advertising in Australia, Malaysia and the United States. METHODS: A consecutive sample of 85 unique advertisements from each country was selected from the advertisements published between January 2004 to December 2006 in three widely circulated medical journals and one prescribing reference manual. The availability of brand name and generic name, indication, contraindications, dosage, side-effects, warnings, interactions and precautions was compared between the three countries. RESULTS: We examined 255 distinct advertisements for 136 pharmaceutical products. Journal advertising in Australia, Malaysia and the US usually provided brand names and generic names (range 96 -100%). Information on dosage was significantly less likely to be mentioned (32%) in the US than in Australia (92%) and Malaysia (48%) (P < 0.001). Warning information was significantly less likely to be provided in Australia (5%) than in the US (81%) and Malaysia (9%) (P < 0.001). Apart from information on brand name, generic name, warnings and dosage, other product information significantly less likely to be provided in journal advertising in Malaysia than in Australia and the US (P < 0.001). Similar trends in the provision of product information for the same medicines published in these countries were noted. Brand name and generic name were always provided in the three countries (100%). However, information on the negative effects of medicines was less frequently provided in Malaysia than in Australia and the US. CONCLUSIONS: Journal advertising in Australia, Malaysia and the US failed to provide complete product information. Low quality of information provided in Malaysia indicates the need for effective regulation of provision of medicines information in journal advertising. Different standards of medicines information provided in these three countries suggest that pharmaceutical promotion needs to be better controlled at the international level.

The Australian funding debate on quadrivalent HPV vaccine: a case study for the national pharmaceutical policy.

OBJECTIVES: To analyse the media and political reactions to the initial decision of the Pharmaceutical Benefits Advisory Committee (PBAC) to reject funding of the quadrivalent human papilloma virus (HPV) vaccine in Australia. METHODS: A case study, informed by media reports and government documents, was utilised to examine the reactions of key stakeholders; PBAC, consumers, consumer organisations, pharmaceutical industry, politicians, health professionals and the media to the initial decision to reject funding of HPV vaccine. RESULTS: The initial decision to reject funding of the HPV vaccine led to unprecedented public response with over 300 newspaper articles and calls by consumers, health professionals and politicians to intervene in the decision making process. Misunderstanding of the decision making process, particularly cost-effectiveness assessments, the need for an independent process, the legislated inability of a timely and transparent response from policy makers and the lack of a risk mitigation strategy all played a role in the public outcry. CONCLUSIONS: Despite 15 years of implementation of cost-effectiveness assessments there is still a need for improving stakeholder understanding of the decision making process and for timely transfer of complete information. Risk mitigation strategies should be considered as part of the communication plan for all decisions.