Abortion Safety and Use with Normally Prescribed Mifepristone in Canada.

BACKGROUND: In the United States, mifepristone is available for medical abortion (for use with misoprostol) only with Risk Evaluation and Mitigation Strategy (REMS) restrictions, despite an absence of evidence to support such restrictions. Mifepristone has been available in Canada with a normal prescription since November 2017. METHODS: Using population-based administrative data from Ontario, Canada, we examined abortion use, safety, and effectiveness using an interrupted time-series analysis comparing trends in incidence before mifepristone was available (January 2012 through December 2016) with trends after its availability without restrictions (November 7, 2017, through March 15, 2020). RESULTS: A total of 195,183 abortions were performed before mifepristone was available and 84,032 after its availability without restrictions. After the availability of mifepristone with a normal prescription, the abortion rate continued to decline, although more slowly than was expected on the basis of trends before mifepristone had been available (adjusted risk difference in time-series analysis, 1.2 per 1000 female residents between 15 and 49 years of age; 95% confidence interval [CI], 1.1 to 1.4), whereas the percentage of abortions provided as medical procedures increased from 2.2% to 31.4% (adjusted risk difference, 28.8 percentage points; 95% CI, 28.0 to 29.7). There were no material changes between the period before mifepristone was available and the nonrestricted period in the incidence of severe adverse events (0.03% vs. 0.04%; adjusted risk difference, 0.01 percentage points; 95% CI, -0.06 to 0.03), complications (0.74% vs. 0.69%; adjusted risk difference, 0.06 percentage points; 95% CI, -0.07 to 0.18), or ectopic pregnancy detected after abortion (0.15% vs. 0.22%; adjusted risk difference, -0.03 percentage points; 95% CI, -0.19 to 0.09). There was a small increase in ongoing intrauterine pregnancy continuing to delivery (adjusted risk difference, 0.08 percentage points; 95% CI, 0.04 to 0.10). CONCLUSIONS: After mifepristone became available as a normal prescription, the abortion rate remained relatively stable, the proportion of abortions provided by medication increased rapidly, and adverse events and complications remained stable, as compared with the period when mifepristone was unavailable. (Funded by the Canadian Institutes of Health Research and the Women's Health Research Institute.)

Improving rural and regional access to long-acting reversible contraception and medical abortion through nurse-led models of care, task-sharing and telehealth (ORIENT): a protocol for a stepped-wedge pragmatic cluster-randomised controlled trial in Australian general practice

INTRODUCTION: Women living in rural and regional Australia often experience difficulties in accessing long-acting reversible contraception (LARC) and medical abortion services. Nurse-led models of care can improve access to these services but have not been evaluated in Australian general practice. The primary aim of the ORIENT trial (ImprOving Rural and regIonal accEss to long acting reversible contraceptioN and medical abortion through nurse-led models of care, Tasksharing and telehealth) is to assess the effectiveness of a nurse-led model of care in general practice at increasing uptake of LARC and improving access to medical abortion in rural and regional areas. METHODS AND ANALYSIS: ORIENT is a stepped-wedge pragmatic cluster-randomised controlled trial. We will enrol 32 general practices (clusters) in rural or regional Australia, that have at least two general practitioners, one practice nurse and one practice manager. The nurse-led model of care (the intervention) will be codesigned with key women's health stakeholders. Clusters will be randomised to implement the model sequentially, with the comparator being usual care. Clusters will receive implementation support through clinical upskilling, educational outreach and engagement in an online community of practice. The primary outcome is the change in the rate of LARC prescribing comparing control and intervention phases; secondary outcomes include change in the rate of medical abortion prescribing and provision of related telehealth services. A within-trial economic analysis will determine the relative costs and benefits of the model on the prescribing rates of LARC and medical abortion compared with usual care. A realist evaluation will provide contextual information regarding model implementation informing considerations for scale-up. Supporting nurses to work to their full scope of practice has the potential to increase LARC and medical abortion access in rural and regional Australia. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Monash University Human Research Ethics Committee (Project ID: 29476). Findings will be disseminated via multiple avenues including a knowledge exchange workshop, policy briefs, conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622000086763)

Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial.

BACKGROUND: Elevated blood pressure incurs a major health and economic burden, particularly in low-income and middle-income countries. The Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial showed a greater reduction in blood pressure in patients using fixed-combination, low-dose, triple-pill antihypertensive therapy (consisting of amlodipine, telmisartan, and chlorthalidone) than in those receiving usual care in Sri Lanka. We aimed to assess the cost-effectiveness of the triple-pill strategy. METHODS: We did a within-trial (6-month) and modelled (10-year) economic evaluation of the TRIUMPH trial, using the health system perspective. Health-care costs, reported in 2017 US dollars, were determined from trial records and published literature. A discrete-time simulation model was developed, extrapolating trial findings of reduced systolic blood pressure to 10-year health-care costs, cardiovascular disease events, and mortality. The primary outcomes were the proportion of people reaching blood pressure targets (at 6 months from baseline) and disability-adjusted life-years (DALYs) averted (at 10 years from baseline). Incremental cost-effectiveness ratios were calculated to estimate the cost per additional participant achieving target blood pressure at 6 months and cost per DALY averted over 10 years. FINDINGS: The triple-pill strategy, compared with usual care, cost an additional US$9·63 (95$347·75 (285·55 to 412·54) per person in the modelled analysis. Incremental cost-effectiveness ratios were estimated at $7·93 (95$2842·79 (-28·67 to 5714·24) per DALY averted over a 10-year period. INTERPRETATION: Compared with usual care, the triple-pill strategy is cost-effective for patients with mild-to-moderate hypertension. Scaled up investment in the triple pill for hypertension management in Sri Lanka should be supported to address the high population burden of cardiovascular disease. FUNDING: Australian National Health and Medical Research Council

An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial

Background: Cardiovascular diseases (CVD) are responsible for significant morbidity, premature mortality, and economic burden. Despite established evidence that supports the use of preventive medications among patients at high CVD risk, treatment gaps remain. Building on prior evidence and a theoretical framework, a complex intervention has been designed to address these gaps among high-risk, under-treated patients in the Australian primary care setting. This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities; availability of a range of CVD polypills (fixed-dose combinations of two blood pressure lowering agents, a statin ± aspirin) for prescription when appropriate; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification. Methods: Following a systematic development process, the intervention will be evaluated in a pragmatic cluster randomized controlled trial including 70 general practices for a median period of 18 months. The 35 general practices in the intervention group will work with a nominated partner pharmacy, whereas those in the control group will provide usual care without access to the intervention tools. The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels at the study end. The outcomes will be analyzed using data from electronic medical records, utilizing a validated extraction tool. Detailed process and economic evaluations will also be performed. Discussion: The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients, pharmacists, and general practitioners (GPs) for CVD prevention. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN1261600023342

Healthcare expenditure on Indigenous and non-Indigenous Australians at high risk of cardiovascular disease

Background: In spite of bearing a heavier burden of death, disease and disability, there is mixed evidence as to whether Indigenous Australians utilise more or less healthcare services than other Australians given their elevated risk level. This study analyses the Medicare expenditure and its predictors in a cohort of Indigenous and non-Indigenous Australians at high risk of cardiovascular disease. Methods: The healthcare expenditure of participants of the Kanyini Guidelines Adherence with the Polypill (GAP) pragmatic randomised controlled trial was modelled using linear regression methods. 535 adult (48% Indigenous) participants at high risk of cardiovascular disease (CVD) were recruited through 33 primary healthcare services (including 12 Aboriginal Medical Services) across Australia. Results: There was no significant difference in the expenditure of Indigenous and non-Indigenous participants in non-remote areas following adjustment for individual characteristics. Indigenous individuals living in remote areas had lower MBS expenditure ($932 per year P< 0.001) than other individuals. MBS expenditure was found to increase with being aged over 65 years ($128, p=0.013), being female ($472, p=0.003), lower baseline reported quality of life ($102 per 0.1 decrement of utility p=0.004) and a history of diabetes ($324, p=0.001), gout ($631, p=0.022), chronic obstructive pulmonary disease ($469, p=0.019) and established CVD whether receiving guideline-recommended treatment prior to the trial ($452, p=0.005) or not ($483, p=0.04). When controlling for all other characteristics, morbidly obese patients had lower MBS expenditure than other individuals (-$887, p=0.002). Conclusion: The findings suggest that for the majority of participants, once individuals are engaged with a primary care provider, factors other than whether they are Indigenous determine the level of Medicare expenditure for each person. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN 126080005833347

Integrative review of managed entry agreements : chances and limitations

Introduction: Managed Entry Agreements (MEAs) consist of a set of instruments to reduce the uncertainty and the budget impact of new high priced medicines; however, there are concerns. There is a need to critically appraise MEAs with their planned introduction in Brazil. Accordingly, the objective is to identify and appraise key attributes and concerns with MEAs among payers and their advisers, with the findings providing critical considerations for Brazil and other high- and middle-income countries. Methods: An integrative review approach was adopted. This involved a review of MEAs across countries. The review question was ‘What are the health technology MEAs that have been applied around the world?’ This review was supplemented with studies not retrieved in the search known to the senior level co-authors including key South American markets. Afterall, involved senior level decision makers and advisers providing guidance on potential advantages and disadvantages of MEAs and ways forward. Results: 25 studies were included in the review. Most MEAs included medicines (96.8%), focused on financial arrangements (43%), and included mostly antineoplastic medicines. Most countries kept key information confidential including discounts or had not published such data. Few details were found in the literature regarding South America. Our findings and inputs resulted in both advantages including reimbursement and disadvantages including concerns with data collection for outcome-based schemes. Conclusion: We are likely to see a growth in MEAs with the continual launch of new high priced and often complex treatments, coupled with increasing demands on resources. Whilst outcome based MEAs could be an important tool to improve access to new innovative medicines there are critical issues to address. Comparing knowledge, experiences and practices across countries is crucial to guide high- and middle-income countries when designing their future MEAs

Medication Adherence in Chronic Disease

Background: Chronic disease places a substantial health and economic burden on individuals and health systems globally. Effective chronic disease management relies on patient adherence to proven medications. Medication adherence rates in chronic disease are sub-optimal, yet adherence-enhancing intervention results are underwhelming. Potentially, current strategies are not matching patient adherence preferences, nor addressing heterogeneity in adherence behaviour between social groups. To inform effective intervention design, this thesis aimed to explore adherence preferences for chronic disease medications and to investigate the effectiveness of adherence-enhancing strategies in socioeconomically disadvantaged groups. Methods: Two discrete choice experiments (DCEs) and a qualitative study were conducted to explore adherence preferences within Australia. A systematic review exploring the effect of strategies aimed at improving adherence to cardiovascular disease medications in socioeconomically disadvantaged populations was conducted. Results and conclusions: Intentional medication decisions were a product of trading between treatment-related factors, particularly cost, treatment scheduling, medication harms and long-term benefits. A patient’s attitudes towards medications, expectations of prescribers and their social context shaped adherence preferences and behaviour. The findings do not support a one-size-fits-all approach to adherence-enhancing interventions. By accounting for heterogeneity in behaviour and critically addressing patient-perceived safety of medications, significant improvements in adherence within the Australian healthcare setting may be achieved

Prescription drug monitoring programs – why are clinicians cautious of this digital health tool and data?

Background: Prescription drug monitoring program (PDMP) systems are used internationally to monitor and reduce harm from high-risk psychoactive prescription medications that are often implicated in prescription shopping, diversion, misuse, and overdoses. PDMP systems facilitate tracking of medications and trigger alerts to assist clinicians in identifying high- or at-risk patients. Systematic reviews have shown varied results with respect to PDMP systems improving prescribing, dispensing, and safety outcomes.  Poor uptake of PDMP technology appears to be a key factor contributing to failure to achieve benefits.  Aim: To collate findings from process evaluations of PDMP to identify the main barriers and facilitators to adoption of these systems.Methods: A systematic review was conducted to identify all systematic reviews of PDMP published after 2015.Results: Only four reviews of PDMP process evaluation studies were identified, all conducted within the United States. Process outcomes examined varied across studies, but in all cases PDMP was underutilised by health care providers. Positive attitudes towards PDMP and knowledge of PDMP positively influenced the likelihood of PDMP use. One review identified a large number of barriers (n=142) and facilitators (n=183) to PDMP which related to information quality, use, intention to use, and user satisfaction. Low PDMP implementation rates related to PDMP infrastructure and data availability challenges.Conclusions: There is a paucity of research comprising process evaluations of PDMP systems.  To understand how and why these systems are achieving or not achieving anticipated outcomes, more studies are needed which assess and describe PDMP use and user experience, including in Australia

Understanding if, how and why non-adherent decisions are made in an Australian community sample : a key to sustaining medication adherence in chronic disease?

Background: Adherence to medications for chronic disease is sub-optimal. Current adherence-enhancing strategies do not seem to adequately address the fundamental need to sustain adherence or prevent non-adherence. Intentional non-adherence, involving active medication-taking decisions, is not well described within the Australian community setting. Understanding if, how and why non-adherent decisions are made may help develop strategies to sustain adherence in chronic disease. Objective: This study aimed to describe intentional non-adherent behavior in chronic disease within the Australian community setting and identify the factors that promote and prevent non-adherent decisions. Methods: In-depth, semi-structured interviews were conducted with 21 patients (12 rural, 9 metropolitan; New South Wales) prescribed medications for a diverse range of chronic conditions. Using the Theory of Planned Behavior as the theoretical framework, an iterative thematic framework analysis method was used to characterize the intentions and the decisions underlying non-adherent behavior. Data were indexed and charted within the thematic framework using Excel, and linked themes were combined, and associations and explanations drawn. Results: Although there was a strong intent to follow prescribers' recommendations, most patients described instances of intentionally non-adherent behavior. Trading between perceived treatment inefficacy, unfavorable side effects and unaffordable medication costs promoted non-adherent decisions; trusting prescriber–patient relationships, positive family values and lack of perceived control over treatment choice maintained adherent intentions. Intentional non-adherence was mostly temporary. Conclusions: Intentional medication non-adherence in chronic disease appears reversible and amenable to interventions that address treatment-related barriers such as medication affordability. Strategies that strengthen patient–prescriber relationships and empower patients as informed decision-makers may help maintain adherence intentions. Crucially, regular and sustained interventions that are refreshed to meet the changing needs of patients are needed to curb the temporal decline in adherence to chronic disease medications.9 page(s