Recent trends in incidence, survival and treatment of multiple myeloma in Finland - a nationwide cohort study.

This study aimed to determine the incidence and prevalence of multiple myeloma (MM) in Finland in 2015-2019, to characterize adult patients newly diagnosed with MM, and to follow-up their overall survival (OS) and treatment patterns until the end of 2020. We sourced the data on inpatient and outpatient diagnoses, outpatient medication use, and date of death from comprehensive, nationwide registers. We identified 2037 incident patients with MM in 2015-2019. On average, the annual crude incidence was 8.8 and the age-standardized incidence (World Standard Population) was 3.3 per 100,000. The crude prevalence at the end of 2019 was 32.7 cases per 100,000 inhabitants ≥ 18 years of age. Median age of the patients at first diagnosis (index date) was 71 years, and 48% were female, the median follow-up being 2.4 years. The median OS was estimated at 4.5 years. The proportion of the patients receiving autologous stem cell transplantation (ASCT) within one year since the index date was 24%, with little variation across study years. Conversely, the proportion of all patients receiving lenalidomide within one year since the index date increased from 27 to 48% overall, and from 39 to 81% among ASCT recipients. The estimated median relapse-free survival after ASCT was 2.9 years. Information on in-hospital MM medication administrations was available for a subset of the study cohort. In this subset, 85.8% of the patients received immunomodulatory drugs and/or proteasome inhibitors within the first year after the index date.

Reimbursement and use of oral anticoagulants during 2014-2022 - A register-based study.

Background: Vitamin K antagonists, warfarin in particular, have been the mainstay of anticoagulation therapy, but their use has declined in many countries since direct oral anticoagulants (DOACs) have entered the market. Objective: To examine utilization trends of oral anticoagulants (OACs) in Finland considering the reimbursement of DOACs and changes to national treatment guidelines for the treatment of atrial fibrillation (AF). Methods: Both public, aggregated data on reimbursed OAC dispensations and individual-level data on electronic dispensations during 2014-2022 were applied. Data on electronic dispensations during 2015-2016 were used to study OAC initiations. Data on entitlements to reimbursement for DOACs came from public data. Results: In 2014, there were almost 20,000 DOAC users, rising to 214,000 in 2022. The number of warfarin users declined since 2015 from over 181,000 to around 59,000 users in 2022, DOACs exceeding warfarin in the number of users in 2019. The total DOAC costs were higher than warfarin costs each year. Rivaroxaban was the most widely used DOAC during 2014-2018, and apixaban during 2019-2022. In 2015, there were more warfarin (56.7%) than DOAC (43.3%) initiators, but the result was opposite for 2016 (warfarin 39.4%, DOACs 60.6%). The number of individuals entitled to reimbursement for DOACs has increased steadily, and in 2022, there were over 196,000 individuals entitled to this reimbursement due to AF. Conclusions: The uptake of DOACs in Finland appears to have been gradual and slower than in many other countries. During the 2010s, the treatment guidelines for AF were more cautious in recommending DOACs than the European guidelines. The use of DOACs increased as their reimbursement became less restrictive.

The changing pattern of statin use in people with dementia: A population-based study.

BACKGROUND: After a dementia diagnosis, goals of care are often reassessed, including the use of preventive medications like statins. OBJECTIVE: To examine changes in statin use after initiating medication for managing dementia. METHODS: A case-crossover study utilizing medication dispensing data from the Australian Pharmaceutical Benefits Scheme (PBS) 10% random sample was conducted. Use of statins was compared in the 12 months pre- and post-initiation (pre-period and post-period) of anti-dementia medications or risperidone for behavioural symptoms of dementia. Individuals aged ≥65 years who had their first dispensing of anti-dementia medication or risperidone between July 2006 and June 2017 and survived ≥12 months after their first supply were included. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for change in statin use in the discordant pairs. RESULTS: The cohort (n = 19,809) had a median age of 81 years and 61% were female. Statins were less likely to be used after initiating anti-dementia medication or risperidone (OR 0.50; 95%CI 0.45-0.55). The OR for statin use in the post-period versus the pre-period decreased annually over the 11 years from 1.21; 95%CI 0.84-1.75 in 2006-7 to 0.31; 95%CI 0.24-0.41 in 2016-17 (p for interaction <0.05). CONCLUSION: Statins are more likely to be ceased than started after initiating medication for dementia. This may reflect changes in goals of care, or changes in the interpretation of the available evidence for the safety and efficacy of statins in older people living with dementia.

Real-world adherence, persistence, and in-class switching during use of dipeptidyl peptidase-4 inhibitors: a systematic review and meta-analysis involving 594,138 patients with type 2 diabetes.

AIMS: Medication adherence and persistence are important determinants of treatment success in type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis evaluated the real-world adherence, persistence, and in-class switching among patients with T2DM prescribed dipeptidyl peptidase-4 (DPP4) inhibitors. METHODS: MEDLINE, EMBASE, Cochrane Library, PsychINFO, and CINAHL were searched for relevant observational studies published in the English language up to 20 December 2019. This was supplemented by manual screening of the references of included papers. Random-effects meta-analysis was performed. RESULTS: Thirty-four cohort studies involving 594,138 patients with T2DM prescribed DPP4 inhibitors from ten countries were included. The pooled proportion adherent (proportion of days covered (PDC) or medication possession ratio (MPR) ≥ 0.80) was 56.9% (95% confidence interval [CI] 49.3-64.4) at one year and 44.2% (95% CI 36.4-52.1) at two years. The proportion persistent with treatment decreased from 75.6% (95% CI 71.5-79.5) at six months to 52.8% (95% CI 51.6-59.8) at two years. No significant differences in adherence and persistence were observed between individual DPP4 inhibitors. At one year, just 3.2% (95% CI 3.1-3.3) of patients switched from one DPP4 inhibitor to another. Switching from saxagliptin and alogliptin to others was commonest. CONCLUSIONS: Adherence to and persistence with DPP4 inhibitors is suboptimal but similar across all medications within the class. While in-class switching is uncommon, saxagliptin and alogliptin are the DPP4 inhibitors most commonly switched. Interventions to improve treatment adherence and persistence among patients with T2DM prescribed DPP4 inhibitors may be warranted.

Frailty and Co-Prescribing of Potentially Interacting Drugs in New Users of Warfarin.

BACKGROUND: Warfarin is underutilised in frail older people because of the fear of bleeding complications. Drug interactions are an independent bleeding risk factor. However, the extent to which potential drug interactions are taken into account at warfarin therapy initiation in frail patients is not known. OBJECTIVE: The objective of this study was to investigate the use of potentially interacting drugs increasing the bleeding risk before and after warfarin initiation in frail and non-frail patients. METHODS: We conducted an observational study including inpatients aged ≥ 60 years initiated on warfarin in a tertiary hospital in Adelaide, South Australia. Frailty status was assessed with the Reported Edmonton Frail Scale. Medication charts were reviewed before and after warfarin initiation. RESULTS: In total, 151 patients (102 non-frail and 49 frail) were included. Before warfarin initiation, the use of clopidogrel and acetaminophen was more common in frail patients compared with non-frail patients (25.5% vs 10.2%, p = 0.0135, 63.8% vs 35.7% p = 0.0014, respectively). The use of non-steroidal anti-inflammatory drugs, 9.2% in non-frail patients and 6.4% in frail patients before warfarin initiation, was completely stopped after warfarin initiation in both groups. The use of antiplatelet drugs decreased from 56.1% in non-frail patients and 66.0 % in frail patients to 12.2% and 14.9%, respectively. Instead, the use of drugs affecting the metabolism of warfarin or vitamin K increased in both groups. No statistically significant difference was seen in the exposure to interacting drugs between study groups after warfarin initiation. Acetaminophen, senna glycosides and cytochrome P450 2C9 inhibiting drugs were the most common interacting drugs at discharge used in 49.0%, 18.4% and 20.4% of non-frail patients and 53.2%, 29.8% and 19.1% of frail patients, respectively. CONCLUSIONS: The overall frequency of potential drug interactions was moderate and frail patients were not exposed to warfarin drug interactions more often than non-frail patients. Further studies in larger study populations are required to verify these results.

Lifestyle Changes in Relation to Initiation of Antihypertensive and Lipid-Lowering Medication: A Cohort Study.

Background Lifestyle modification is a key component of cardiovascular disease prevention before and concurrently with pharmacologic interventions. We evaluated whether lifestyle factors change in relation to the initiation of antihypertensive or lipid-lowering medication (statins). Methods and Results The study population comprised 41 225 participants of the FPS (Finnish Public Sector) study aged ≥40 years who were free of cardiovascular disease at baseline and responded to ≥2 consecutive surveys administered in 4-year intervals in 2000-2013. Medication use was ascertained through pharmacy-claims data. Using a series of pre-post data sets, we compared changes in body mass index, physical activity, alcohol consumption, and smoking between 8837 initiators and 46 021 noninitiators of antihypertensive medications or statins. In participants who initiated medication use, body mass index increased more (difference in change 0.19; 95% CI, 0.16-0.22) and physical activity declined (-0.09 metabolic equivalent of task hour/day; 95% CI, -0.16 to -0.02) compared with noninitiators. The likelihood of becoming obese (odds ratio: 1.82; 95% CI, 1.63-2.03) and physically inactive (odds ratio: 1.08; 95% CI, 1.01-1.17) was higher in initiators. However, medication initiation was associated with greater decline in average alcohol consumption (-1.85 g/week; 95% CI, -3.67 to -0.14) and higher odds of quitting smoking (odds ratio for current smoking in the second survey: 0.74; 95% CI, 0.64-0.85). Conclusions These findings suggest that initiation of antihypertensive and statin medication is associated with lifestyle changes, some favorable and others unfavorable. Weight management and physical activity should be encouraged in individuals prescribed these medications.

First insight to the Finnish nationwide electronic prescription database as a data source for pharmacoepidemiology research.

BACKGROUND: Since 1994, the Finnish Prescription Register (FPR) has been the main data source for pharmacoepidemiology research in Finland. However, the FPR data are limited to reimbursed dispensations only. Implementation of electronic prescribing started in 2010 and after a stepwise extension, electronic prescribing became mandatory in all healthcare settings in 2017. Prescriptions issued and dispensed electronically are stored in the Prescription Centre of the nationwide Kanta database. OBJECTIVES: To describe the contents of the Kanta database and to compare the coverage of Kanta with the FPR, using prescriptions and dispensations of oral anticoagulants (OACs) as an example. METHODS: All prescriptions, dispensations, and their cancellations and corrections for OACs recorded in Kanta were retrieved for the period 2012-2016. RESULTS: In 2016, the total number of valid electronic prescriptions for OACs was 249 139 and the number of valid electronic OAC dispensations was 765 745. The number of identified direct oral anticoagulant (DOAC) users was higher in Kanta compared to the FPR since 2014, although more users of all OACs were identified from the FPR during 2012-2015. In 2016, an indication was identified in 44.7% of OAC prescriptions and dosing instructions in 99.5% of DOAC prescriptions. CONCLUSIONS: The Kanta database is a promising source of data on medication exposure. Because of reimbursement restrictions, use of DOACs was under-ascertained through the FPR.

Global Incidence of Frailty and Prefrailty Among Community-Dwelling Older Adults: A Systematic Review and Meta-analysis.

Importance: Frailty is a common geriatric syndrome of significant public health importance, yet there is limited understanding of the risk of frailty development at a population level. Objective: To estimate the global incidence of frailty and prefrailty among community-dwelling adults 60 years or older. Data Sources: MEDLINE, Embase, PsycINFO, Web of Science, CINAHL Plus, and AMED (Allied and Complementary Medicine Database) were searched from inception to January 2019 without language restrictions using combinations of the keywords frailty, older adults, and incidence. The reference lists of eligible studies were hand searched. Study Selection: In the systematic review, 2 authors undertook the search, article screening, and study selection. Cohort studies that reported or had sufficient data to compute incidence of frailty or prefrailty among community-dwelling adults 60 years or older at baseline were eligible. Data Extraction and Synthesis: The methodological quality of included studies was assessed using The Joanna Briggs Institute's Critical Appraisal Checklist for Prevalence and Incidence Studies. Meta-analysis was conducted using a random-effects (DerSimonian and Laird) model. Main Outcomes and Measures: Incidence of frailty (defined as new cases of frailty among robust or prefrail individuals) and incidence of prefrailty (defined as new cases of prefrailty among robust individuals), both over a specified duration. Results: Of 15 176 retrieved references, 46 observational studies involving 120 805 nonfrail (robust or prefrail) participants from 28 countries were included in this systematic review. Among the nonfrail individuals who survived a median follow-up of 3.0 (range, 1.0-11.7) years, 13.6% (13 678 of 100 313) became frail, with the pooled incidence rate being 43.4 (95% CI, 37.3-50.4; I2 = 98.5%) cases per 1000 person-years. The incidence of frailty was significantly higher in prefrail individuals than robust individuals (pooled incidence rates, 62.7 [95% CI, 49.2-79.8; I2 = 97.8%] vs 12.0 [95% CI, 8.2-17.5; I2 = 94.9%] cases per 1000 person-years, respectively; P for difference < .001). Among robust individuals in 21 studies who survived a median follow-up of 2.5 (range, 1.0-10.0) years, 30.9% (9974 of 32 268) became prefrail, with the pooled incidence rate being 150.6 (95% CI, 123.3-184.1; I2 = 98.9%) cases per 1000 person-years. The frailty and prefrailty incidence rates were significantly higher in women than men (frailty: 44.8 [95% CI, 36.7-61.3; I2 = 97.9%] vs 24.3 [95% CI, 19.6-30.1; I2 = 8.94%] cases per 1000 person-years; prefrailty: 173.2 [95% CI, 87.9-341.2; I2 = 99.1%] vs 129.0 [95% CI, 73.8-225.0; I2 = 98.5%] cases per 1000 person-years). The incidence rates varied by diagnostic criteria and country income level. The frailty and prefrailty incidence rates were significantly reduced when accounting for the risk of death. Conclusions and Relevance: Results of this study suggest that community-dwelling older adults are prone to developing frailty. Increased awareness of the factors that confer high risk of frailty in this population subgroup is vital to inform the design of interventions to prevent frailty and to minimize its consequences.

Trends and Predictors of Oral Anticoagulant Use in People with Alzheimer's Disease and the General Population in Australia.

BACKGROUND: People with Alzheimer's disease (AD) are less likely to use oral anticoagulants than people without AD. OBJECTIVE: We investigated incidence and prevalence of warfarin and direct oral anticoagulant (DOAC) use, and determined predictors of DOAC and warfarin initiation in older people with AD and the general population. METHODS: Australian Pharmaceutical Benefits Scheme data for 356,000 people aged ≥65 years dispensed warfarin or DOACs during July 2013-June 2017 were analyzed. Changes in annual incidence and prevalence were estimated using Poisson regression. Predictors of DOAC versus warfarin initiation were estimated using multivariable logistic regression separately for people with AD and the general population. RESULTS: Oral anticoagulant prevalence increased from 8% in people with AD and 9% in the general population to 12% in both groups from 2013/2014 to 2016/2017. DOAC prevalence increased (from 2.4% to 7.8% in people with AD, 3.2% to 7.7% in the general population) while warfarin prevalence declined (6.6% to 4.5%, 7.0% to 4.3%, correspondingly). The incidence of warfarin use decreased by 45-55%. In people with AD, women were less likely to initiate DOACs than men, whereas presence of arrhythmias or pain/inflammation increased likelihood of initiating DOACs. Age ≥85 years, cardiovascular diseases, gastric acid disorder, diabetes, and end-stage renal disease were associated with lower odds of DOAC initiation in the general population. CONCLUSION: DOAC introduction has coincided with increased anticoagulation rates in people with AD. Rates are now similar in older people with AD and the general population. Compared to previous years, DOACs are now more likely to be initiated, particularly for those aged ≥85 years.

Patterns of High-Dose and Long-Term Proton Pump Inhibitor Use: A Cross-Sectional Study in Six South Australian Residential Aged Care Services.

AIM: While proton pump inhibitors (PPIs) are generally considered safe and well tolerated, frail older people who take PPIs long term may be susceptible to adverse events. This study characterized PPI use and determined factors associated with high-dose use among older adults in residential aged care services (RACSs). METHODS: A cross-sectional study of 383 residents of six South Australian RACSs within the same organization was conducted. Clinical, diagnostic, and medication data were collected by study nurses. The proportions of residents who took a PPI for > 8 weeks and without documented indications were calculated. Factors associated with high-dose PPI use compared to standard/low doses were identified using age- and sex-adjusted logistic regression models. RESULTS: 196 (51%) residents received a PPI, with 45 (23%) prescribed a high dose. Overall, 173 (88%) PPI users had documented clinical indications or received medications that can increase bleeding risk. Three-quarters of PPI users with gastroesophageal reflux disease or dyspepsia had received a PPI for > 8 weeks. High-dose PPI use was associated with increasing medication regimen complexity [odds ratio (OR) 1.02; 95% confidence interval (CI) 1.01-1.04 per one-point increase in Medication Regimen Complexity Index score] and a greater number of medications prescribed for regular use (OR 1.11; 95% CI 1.01-1.21 per additional medication). CONCLUSIONS: Half of all residents received a PPI, of whom the majority had documented clinical indications or received medications that may increase bleeding risk. There remains an opportunity to review the continuing need for treatment and consider "step-down" approaches for high-dose PPI users.

Prevalence and incidence of prescription opioid analgesic use in Australia.

AIMS: The aims of the current study were to determine the prevalence and incidence of prescription opioid analgesic use in Australia and compare the characteristics of people with and without cancer initiating prescription opioid analgesics. METHODS: A retrospective population-based study was conducted using the random 10% sample of adults who were dispensed prescription opioid analgesics in Australia between July 2013 and June 2017 through the Pharmaceutical Benefits Scheme. Poisson regression was used to calculate rate ratios (RR) for opioid prevalence and incidence. The characteristics of people initiating opioids, including type of opioid initiated, total oral morphine equivalents dispensed, prescriber speciality, medical comorbidities, and past analgesic and benzodiazepine use, were compared for people with and without cancer. RESULTS: Opioid prevalence increased {RR = 1.006 [95% confidence interval (CI) 1.004, 1.008]}, while incidence decreased [RR = 0.977 (95% CI 0.975,0.979)] from 2013/2014 to 2016/2017. There were between 287 677 and 307 772 prevalent users each year. In total, 769 334 adults initiated opioids between 2013/2014 and 2016/2017, and half of these initiations were by general practitioners. Initiation with a strong opioid occurred in 55.8% of those with cancer and 28.2% of those without cancer. CONCLUSION: Rates of opioid use have remained high since 2013, with approximately 3 million adults using opioids and over 1.9 million adults initiating opioids each year. Between 2013 and 2017, opioid prevalence has slightly increased but incidence has decreased. People without cancer account for the majority of opioid use and are more likely to be initiated on short-acting and weak opioids. Initiation of strong opioids has increased over time, reinforcing concerns about increased use and the harms associated with strong opioids in the community.

Physicians' views on patient participation in choice of oral anticoagulants in atrial fibrillation-a qualitative study.

Direct oral anticoagulants provide an alternative to vitamin K antagonists for the anticoagulation therapy in atrial fibrillation (AF). The availability of several treatment options with different attributes makes shared decision-making appropriate for the choice of anticoagulation therapy. The aim of this study was to understand how physicians choose an oral anticoagulant (OAC) for patients with AF and how physicians view patients' participation in this decision. Semi-structured interviews with 17 Finnish physicians (eight general practitioners and nine specialists) working in the public sector were conducted. An interview guide on experience, prescribing and opinions about oral anticoagulants was developed based on previous literature. The data were thematically analysed using deductive and inductive approaches. Based on the interviews, patient's opinion was the most influential factor in decision-making when there were no clinical factors limiting the choice between OACs. Of patient's preferences, the most important was the attitude towards co-payments of OACs. Patients' opinions on monitoring of treatment, dosing and antidote availability were also mentioned by the interviewees. The choice of an OAC in AF was patient-centred as all interviewees expressed that patient's opinion affects the choice.

Demographic, clinical and lifestyle factors associated with high-intensity statin therapy in Australia: the AusDiab study.

PURPOSE: Clinical guidelines specify who should receive high-intensity statins; however, it is unclear how high-intensity statins are used in Australia. Our objective was to determine the demographic, clinical, and lifestyle factors associated with high-intensity statin therapy in Australia. METHODS: Data from the Australian Diabetes, Obesity and Lifestyle study collected in 2011-2012 were analyzed. High-, moderate-, and low-intensity statins were defined as use of statins at doses demonstrated to reduce low-density lipoprotein cholesterol levels by > 50, 30-50, and < 30%, respectively. Logistic regression was used to estimate adjusted odd ratios (ORs) and 95% confidence intervals (CIs) for factors associated with high- versus low-to-moderate-intensity statin therapy. RESULTS: Overall, 1108 (24%) study participants used a statin. Data on statin intensity were available for 1072 participants. The proportions of high-, moderate-, and low-intensity statin therapy were 32 (n = 341), 65 (n = 696), and 3% (n = 35), respectively. Overall, 51% of people with prior cardiovascular disease (CVD) used a high-intensity statin. In addition to prior CVD (OR = 3.34, 95% CI = 1.95-5.73), no (OR = 1.84, 95%CI 1.02-3.31) or insufficient physical activity (OR = 1.51, 95% CI = 1.01-2.25), obesity (OR = 1.87, 95% CI = 1.13-3.10), and consuming > 2 alcoholic drinks daily (OR = 1.66, 95% CI = 1.08-2.55) were associated with high versus low-to-moderate-intensity statin therapy. Conversely, age 65-74 vs. < 65 years was inversely associated with high-intensity statin therapy (OR = 0.62, 95% CI = 0.41-0.94). CONCLUSIONS: Prior CVD was the strongest factor associated with high-intensity statin therapy. Although the prevalence of CVD increases with age, older people were less likely to be treated with high-intensity statins.

Selective prescribing of statins and the risk of mortality, hospitalizations, and falls in aged care services.

BACKGROUND: Compared to randomized controlled trials, nonexperimental studies often report larger survival benefits but higher rates of adverse events for statin use vs nonuse. OBJECTIVE: We compared characteristics of statin users and nonusers living in aged care services and evaluated the relationships between statin use and all-cause mortality, all-cause and fall-related hospitalizations, and number of falls during a 12-month follow-up. METHODS: A prospective cohort study of 383 residents aged ≥65 years was conducted in six Australian aged care services. Data were obtained from electronic medical records and medication charts and through a series of validated assessments. RESULTS: The greatest differences between statin users and nonusers were observed in activities of daily living, frailty, and medication use (absolute standardized difference >0.40), with users being less dependent and less frail but using a higher number of medications. Statin use was associated with a decreased risk of all-cause mortality (adjusted hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.37-0.93) and hospitalizations (HR 0.67, 95% CI 0.46-0.98). After exclusion of residents unable to sit or stand, statin use was associated with a nonsignificant increase in the risk of fall-related hospitalizations (HR 1.47, 95% CI 0.80-2.68) but with a lower incidence of falls (incidence rate ratio 0.67, 95% CI 0.47-0.96). CONCLUSIONS: The observed associations between statin use and the outcomes may be largely explained by selective prescribing and deprescribing of statins and variation in likelihood of hospitalization based on consideration of each resident's clinical and frailty status. Randomized deprescribing trials are needed to guide statin prescribing in this setting.

Statins do not Increase the Rate of Bleeding Among Warfarin Users.

Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalization among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person-years of exposure to warfarin-only and 60,253 years of exposure to warfarin-with-statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalization. A Poisson generalized estimating equation model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin-with-statin compared to warfarin-only and to allow multiple episodes per patient and time-dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable-adjusted RR = 0.98, 95% CI 0.89-1.07) or to simvastatin (RR = 1.01, 95% CI 0.91-1.11) with warfarin compared to exposure to warfarin-only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalization.

Predictors of persistent prescription opioid analgesic use among people without cancer in Australia.

AIMS: To identify patterns of opioid analgesic use and determine predictors of persistent opioid use among people without cancer. METHODS: A population-based cohort study of Australians initiating prescription opioids from July 2013 to December 2015 was conducted using data from a random 10% sample of people who accessed medicines through Australia's Pharmaceutical Benefits Scheme. A 12-month retrospective period was used to define opioid initiation, exclude people with cancer and determine comorbidities. Persistent use over 12 months since initiation was identified through group-based trajectory modelling. Odds ratios (OR) and 95% confidence intervals (CIs) for predictors of opioid persistence were estimated using logistic regression. RESULTS: The cohort consisted of 431 963 people without cancer who initiated opioids. A total of 11 323 (2.6%) persistent opioid users were identified. Predictors of persistence included initiation with transdermal formulations (OR 4.2, 95% CI 3.9-4.5), or initiation with total oral morphine equivalents (OME) ≥ 750 mg (3.7, 3.3-4.1), having depression (1.6, 1.5-1.7) or psychotic illness (2.0, 1.9-2.2). Previous dispensing of paracetamol (2.0, 1.9-2.1), pregabalin (2.0, 1.8-2.1) and benzodiazepines (1.53, 1.4-1.6) predicted persistence. Compared to people aged 18-44 years, those ≥75 years were 2.5 (2.3-2.6) times more likely to be persistent users. CONCLUSIONS: Patient-specific characteristics (older age, prior history of mental health comorbidities and use of non-opioid analgesics) and prescriber choice of initial opioid (transdermal formulation and higher total OMEs) were found to strongly predict persistent use. This information may help prescribers target monitoring and early intervention efforts in order to prevent harms associated with the long-term use of opioids.

A Systematic Review and Meta-analysis of the Factors Associated With Nonadherence and Discontinuation of Statins Among People Aged ≥65 Years.

Background: Older individuals (aged ≥65 years) are commonly prescribed statins but may experience a range of barriers in adhering to therapy. The factors associated with poor statin adherence and/or discontinuation among this population have not been comprehensively reviewed. Methods: We conducted a systematic review to identify English articles published through December 12, 2016 that reported factors associated with nonadherence and/or discontinuation of statins among older persons. Data were pooled via random-effects meta-analysis techniques. Results: Forty-five articles reporting data from more than 1.8 million older statin users from 13 countries were included. The factors associated with increased statin nonadherence were black/non-white race (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.39-1.98), female gender (OR 1.08, 95% CI 1.03-1.13), current smoker (OR 1.12, 95% CI 1.03-1.21), higher copayments (OR 1.38, 95% CI 1.25-1.52), new user (OR 1.58, 95% CI 1.21-2.07), lower number of concurrent cardiovascular medications (OR 1.08, 95% CI 1.06-1.09), primary prevention (OR 1.49, 95% CI 1.40-1.59), having respiratory disorders (OR 1.17, 95% CI 1.12-1.23) or depression (OR 1.11, 95% CI 1.06-1.16), and not having renal disease (OR 1.09, 95% CI 1.04-1.14). The factors associated with increased statin discontinuation were lower income status (OR 1.20, 95% CI 1.06-1.36), current smoker (OR 1.14, 95% CI 1.06-1.23), higher copayment (OR 1.61, 95% CI 1.53-1.70), higher number of medications (OR 1.04, 95% CI 1.01-1.06), presence of dementia (OR 1.18, 95% CI 1.02-1.36), cancer (OR 1.22, 95% CI 1.11-1.33) or respiratory disorders (OR 1.19, 95% CI 1.05-1.34), primary prevention (OR 1.66, 95% CI 1.24-2.22), and not having hypertension (OR 1.13, 95% CI 1.07-1.20) or diabetes (OR 1.09, 95% CI 1.04-1.15). Conclusion: Interventions that target potentially modifiable factors including financial and social barriers, patients' perceptions about disease risk as well as polypharmacy may improve statin use in the older population.

Adherence and Persistence Among Statin Users Aged 65 Years and Over: A Systematic Review and Meta-analysis.

Background: Older people (aged ≥ 65 years) have distinctive challenges with medication adherence. However, adherence and persistence patterns among older statin users have not been comprehensively reviewed. Methods: As part of a broader systematic review, we searched Medline, Embase, PsycINFO, CINAHL, Database of Abstracts of Reviews of Effects, CENTRAL, and the National Health Service Economic Evaluation Database through December 2016 for English articles reporting adherence and/or persistence among older statin users. Data were analyzed via descriptive methods and meta-analysis using random-effect modeling. Results: Data from more than 3 million older statin users in 82 studies conducted in over 40 countries were analyzed. At 1-year follow-up, 59.7% (primary prevention 47.9%; secondary prevention 62.3%) of users were adherent (medication possession ratio [MPR] or proportion of days covered [PDC] ≥ 80%). For both primary and secondary prevention subjects, 1-year adherence was worse among individuals aged more than 75 years than those aged 65-75 years. At 3 and ≥10 years, 55.3% and 28.4% of users were adherent, respectively. The proportion of users persistent at 1-year was 76.7% (primary prevention 76.0%; secondary prevention 82.6%). Additionally, 68.1% and 61.2% of users were persistent at 2 and 4 years, respectively. Among new statin users, 48.2% were nonadherent and 23.9% discontinued within the first year. The proportion of statin users who were adherent based on self-report was 85.5%. Conclusions: There is poor short and long term adherence and persistence among older statin users. Strategies to improve adherence and reduce discontinuation are needed if the intended cardiovascular benefits of statin treatment are to be realized.

Changes in Statin Adherence Following an Acute Myocardial Infarction Among Older Adults: Patient Predictors and the Association With Follow-Up With Primary Care Providers and/or Cardiologists.

BACKGROUND: Hospitalizations for acute myocardial infarctions (AMIs) are associated with changes in statin adherence. It is unclear to what extent adherence changes, which patients are likely to change, and how post-discharge follow-up is associated with statin adherence change. METHODS AND RESULTS: This retrospective study used Medicare data for all fee-for-service beneficiaries 66 years and older with an AMI hospitalization in 2008-2010 and statin use before their index AMI. Multivariable multinomial logistic regression models (odds ratio [OR] and 99% confidence interval [CI]) were applied to assess associations between both patient characteristics and follow-up with a primary care provider and/or cardiologist with the outcome of statin adherence change (increase or decrease) from the 6-month pre- to 6-month post-AMI periods. Of 113 296 patients, 64.0% had no change in adherence, while 19.7% had increased and 16.3% had decreased adherence after AMI hospitalization. Black and Hispanic patients were more likely to have either increased or decreased adherence than white patients. Patients who required coronary artery bypass graft surgery (OR, 1.34; 99% CI, 1.21-1.49) or percutaneous transluminal coronary angioplasty/stent procedure (OR, 1.25; 99% CI, 1.17-1.32) during their index hospitalization were more likely to have increased adherence. Follow-up with a primary care provider was only mildly associated with increased adherence (OR, 1.08; 99% CI, 1.00-1.16), while follow-up with a cardiologist (OR, 1.15; 99% CI, 1.05-1.25) or both provider types (OR, 1.21; 99% CI, 1.12-1.30) had stronger associations with increased adherence. CONCLUSIONS: Post-AMI changes in statin adherence varied by patient characteristics, and improved adherence was associated with post-discharge follow-up care, particularly with a cardiologist or both a primary care provider and a cardiologist.