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 lipidlowering 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.Peer reviewe

Trajectory analyses of adherence patterns in a real-life moderate to severe asthma population

Background: Global Initiative for Asthma step 5 therapies (GINA-5), other than inhaled corticosteroids and long-acting β-agonists in fixed dose combinations (ICS/LABA FDC), often entail more expensive (eg, monoclonal biologics) or less safe (eg, maintenance oral corticosteroids [OCS]) treatments. It is therefore important to assess poor inhaler adherence as a possible cause of suboptimal response to ICS/LABA FDC before additional GINA-5. Objective: To determine rates of, and time to, additional GINA-5 after first-year ICS/LABA FDC use, and their association with inhaler adherence. Methods: Patients initiating ICS/LABA FDC between 2013 and 2017 were identified from Australian national dispensing data. Group-based trajectory modeling was used to estimate medication adherence patterns. Multivariable Cox proportional hazards models were used to examine the association between adherence trajectories and GINA-5 addition during 2-year follow-up. Results: In total, 3062 new ICS/LABA FDC users were identified, of whom 120 (3.9%) received additional GINA-5 (OCS: 89; long-acting muscarinic antagonists: 39; biologics: &lt;3). Mean time to commencing additional GINA-5 was 705.2 (standard deviation, 1.7) days. Adherence trajectories were nonpersistent use (20%), seasonal use (8%), poor adherence (58%), and good adherence (13%). Although poor adherence was associated with longer time to additional GINA-5 (adjusted hazard ratio: 0.58; 95% confidence interval: 0.35-0.95), over 80% of additional GINA-5 was commenced in poorly adherent patients. Use of ≥2 OCS/antibiotic courses also predicted additional GINA-5. Conclusions: Almost 1 in 20 people with asthma commenced additional GINA-5 after ICS/LABA initiation, most of whom (&gt;80%) were poorly adherent to inhaled preventers. There is a substantial unmet need for inhaler adherence to be addressed before prescribing additional GINA-5.</p

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.</p

Risk of cardiovascular events and death associated with initiation of SGLT2 inhibitors compared with DPP-4 inhibitors:an analysis from the CVD-REAL 2 multinational cohort study

Background Cardiovascular outcome trials have shown cardiovascular benefit with sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors have not shown an effect. We aimed to address knowledge gaps regarding the comparative effectiveness of SGLT2 inhibitor use in clinical practice (with DPP-4 inhibitor use as an active comparator) across a range of cardiovascular risks and in diverse geographical settings. Methods In this comparative cohort study, we used data from clinical practice from 13 countries in the Asia-Pacific, Middle East, European, and North American regions to assess the risk of cardiovascular events and death in adult patients with type 2 diabetes newly initiated on SGLT2 inhibitors compared with those newly initiated on DPP-4 inhibitors. De-identified health records were used to select patients who were initiated on these drug classes between Dec 1, 2012, and May 1, 2016, with follow-up until Dec 31, 2014, to Nov 30, 2017 (full range; dates varied by country). Non-parsimonious propensity scores for SGLT2 inhibitor initiation were developed for each country and patients who were initiated on an SGLT2 inhibitor were matched with those who were initiated on a DPP-4 inhibitor in a 1:1 ratio. Outcomes assessed were hospitalisation for heart failure, all-cause death, myocardial infarction, and stroke. Hazard ratios (HRs) were estimated by country and then pooled in a weighted meta-analysis. Findings Following propensity score matching, 193 124 new users of SGLT2 inhibitors and 193 124 new users of DPP-4 inhibitors were included in the study population. Participants had a mean age of 58 years (SD 12.2), 170 335 (44.1%) of 386 248 were women, and 111933 (30.1%) of 372 262 had established cardiovascular disease. Initiation of an SGLT2 inhibitor versus a DPP-4 inhibitor was associated with substantially lower risks of hospitalisation for heart failure (HR 0.69, 95% CI 0. 61-0. 77; p Interpretation In this large, international, observational study, initiation of SGLT2 inhibitors versus DPP-4 inhibitors was associated with lower risks of heart failure, death, myocardial infarction, and stroke, providing further support for the cardiovascular benefits associated with use of SGLT2 inhibitors in patients with type 2 diabetes. Copyright (C) 2020 Elsevier Ltd. All rights reserved

Global epidemiology of hip fractures: a study protocol using a common analytical platform among multiple countries

INTRODUCTION: Hip fractures are associated with a high burden of morbidity and mortality. Globally, there is wide variation in the incidence of hip fracture in people aged 50 years and older. Longitudinal and cross-geographical comparisons of health data can provide insights on aetiology, risk factors, and healthcare practices. However, systematic reviews of studies that use different methods and study periods do not permit direct comparison across geographical regions. Thus, the objective of this study is to investigate global secular trends in hip fracture incidence, mortality and use of postfracture pharmacological treatment across Asia, Oceania, North and South America, and Western and Northern Europe using a unified methodology applied to health records. METHODS AND ANALYSIS: This retrospective cohort study will use a common protocol and an analytical common data model approach to examine incidence of hip fracture across population-based databases in different geographical regions and healthcare settings. The study period will be from 2005 to 2018 subject to data availability in study sites. Patients aged 50 years and older and hospitalised due to hip fracture during the study period will be included. The primary outcome will be expressed as the annual incidence of hip fracture. Secondary outcomes will be the pharmacological treatment rate and mortality within 12 months following initial hip fracture by year. For the primary outcome, crude and standardised incidence of hip fracture will be reported. Linear regression will be used to test for time trends in the annual incidence. For secondary outcomes, the crude mortality and standardised mortality incidence will be reported. ETHICS AND DISSEMINATION: Each participating site will follow the relevant local ethics and regulatory frameworks for study approval. The results of the study will be submitted for peer-reviewed scientific publications and presented at scientific conferences

Patterns of Medication Dispensation for Multiple Comorbidities among Older Adults in Australia

Background: The increasing burden of chronic (medical) conditions (CCs) is a major issue for healthcare systems across the world. We aimed to examine the changes in the rate of medication dispensation for multiple CCs among Australians aged &#8805;65 years. Methods: A repeated cross-sectional study was performed using the 2013&#8315;2016 Pharmaceutical Benefits Scheme (PBS) data on reimbursed prescriptions for a 10% random sample of the Australian population. Twenty-two CCs were identified via the RxRisk-V tool. The yearly changes in the proportion of older adults dispensed medications for &#8805;2 CCs were determined through Poisson regression modelling using 2013 as the reference year. The occurrence of CC dyads and triads for which medications were dispensed within a 180-day window were characterised, and the observed and expected rate of medication dispensation for each CC dyad or triad were calculated to identify the top 15 combinations. Results: The proportion of older adults dispensed medications for &#8805;2 CCs remained stable from 2013 to 2016, at &gt;79% in each year. The proportion who were dispensed medications for multiple CCs increased with age. No gender differences in the dispensation of medications for multiple CCs were observed. Over 60% had medications dispensed for &#8805;3 CCs. The most frequent CC dyad and triad for which medications were dispensed were dyslipidaemia + hypertension (38.6%) and dyslipidaemia + gastroesophageal reflux disease + hypertension (18.7%), respectively. For the majority of CC dyads and all triads examined, the observed rate of medication dispensation exceeded that expected by chance. Conclusions: A high proportion of older Australians are dispensed medications for multiple CCs, suggestive of multimorbidity. The results reiterate the need for increased research into understanding the causal mechanisms of multimorbidity to inform the design of cost-effective interventions

Prevalence of concomitant use of alcohol and sedative-hypnotic drugs in middle and older aged persons: A systematic review

OBJECTIVE: To systematically review the prevalence of concomitant alcohol and sedative-hypnotic use among middle-aged and older persons. DATA SOURCES: A bibliographic search of English-language literature was performed using MEDLINE, EMBASE, and PsycINFO (January 1990-August 2012). The reference lists of all included articles were screened for additional relevant articles not identified by any of the bibliographic searches. STUDY SELECTION AND DATA EXTRACTION: Population-based studies in which the mean age of participants was 40 years or older were included. For a study to be included in the review, alcohol use had to be reported in terms of the quantity or frequency consumed. Data from included articles were extracted using a standardized data extraction tool. DATA SYNTHESIS: Five population-based studies conducted in North America, 10 in Europe, and 1 in Australia were included in the review. Up to 88% of men and 79% of women who used sedative-hypnotics also consumed alcohol. Up to 28% of those who consumed alcohol were concomitant users of sedative-hypnotics. Alcohol was consumed at higher levels among middle-aged than older persons. Risky drinking (eg, binge drinking, heavy drinking) was more prevalent among middle-aged than older persons. In contrast, sedative-hypnotic use was more prevalent among older persons. CONCLUSIONS: Our review identified a higher prevalence of alcohol consumption among middle-aged than older persons. However, middle-aged persons may experience harm from alcohol/sedative-hypnotic drug interactions due to risky drinking behavior. Despite lower levels of alcohol consumption, older persons may be more susceptible to addictive central nervous system effects than younger persons because of physiologic changes in psychotropic drug and alcohol metabolism. Clinicians should consider patients’ alcohol consumption patterns before prescribing sedative-hypnotic drugs

Adherence, Persistence, and Switching Among People Prescribed Sodium Glucose Co-transporter 2 Inhibitors: A Nationwide Retrospective Cohort Study

Introduction: Non-adherence and non-persistence to diabetes medications are associated with worse clinical outcomes. In this study, we aimed to characterise the 1-year switching, adherence, and persistence patterns among people with diabetes aged 18\ua0years\ua0and older prescribed sodium-glucose co-transporter 2 inhibitors (SGLT2is) in Australia. Methods: Using data from Australia’s national Pharmaceutical Benefits Scheme (PBS), we identified 11,981 adults (mean age 60.9\ua0years; 40.5% female) newly initiated on SGLT2is (5993 dapagliflozin; 5988 empagliflozin) from September 2015 to August 2017. Adherence was assessed via the proportion of days covered (PDC), persistence was defined as\ua0the continuous use of SGLT2i without a gap of ≥ 90\ua0days, and switching was defined as the first change from dapagliflozin to empagliflozin or vice versa. Generalised linear models (GLMs) were used to compare the adherence (PDC = continuous), logistic regression models were used to compare the likelihoods of being adherent (PDC ≥ 0.80), and Cox proportional hazard models were used to compare the likelihoods of persistence and switching between people prescribed empagliflozin and dapagliflozin. Results: Overall, 65.8% (7879/11,981) of people dispensed SGLT2is were adherent (PDC ≥ 0.80) and 72.1% (8644/11,981) were persistent at 12 months. The mean PDC was 0.79 \ub1 0.27. The use of empagliflozin was associated with higher adherence (PDC = continuous) [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.03–1.05], being adherent (OR 1.39, 95% CI 1.29–1.51), and persisting for 12 months [hazard ratio (HR) 1.14, 95% CI 1.06–1.22] compared with dapagliflozin. Only 4.3% (509/11,981) of people switched between the SGLT2i. Compared with dapagliflozin, people initiated on empagliflozin were less likely to switch [HR 0.46, 95% CI 0.38–0.55]. Conclusions: A considerable proportion of Australians prescribed SGLT2is were non-adherent or non-persistent. However, empagliflozin was associated with better adherence and persistence rates and a lower likelihood of switching compared with dapagliflozin

Hospital Admissions due to Dysglycaemia and Prescriptions of Antidiabetic Medications in England and Wales:An Ecological Study

INTRODUCTION: Hypoglycaemia and hyperglycaemia are common adverse events associated with antidiabetic medications. They are also a common cause of hospital admissions for people with diabetes. The objective of the study was to explore the trends in hospital admissions due to hypoglycaemia and hyperglycaemia and in the prescriptions of antidiabetic medications in England and Wales. METHODS: We conducted an observational study during the period 1999–2016. Hospital admission data for patients from all age groups were extracted from the Hospital Episode Statistics database in England and the Patient Episode Database for Wales. Data on prescriptions of antidiabetic medications were extracted from the Prescription Cost Analysis database from 2004 to 2016. RESULTS: Between 1999 and 2016, the hospital admission rate increased by 173.0% [from 17.2 (95% CI 16.9–17.6) to 47.1 (95% CI 46.5–47.6) per 100,000 persons] for hypoglycaemia and by 147.0% [from 22.8 (95% CI 22.4–23.2) to 56.3 (95% CI 55.7–56.9) per 100,000 persons] for hyperglycaemia. The prescription rate for all antidiabetic medications increased between 2004 and 2016 by 116.0% [from 373.0 (95% CI 373.0–373.0) to 806.0 (95% CI 806.0–806.0) prescriptions per 1000 persons]. There was a parallel increase in the rate of antidiabetic medication prescriptions during the same study period, with correlation coefficients of 0.94 for hypoglycaemia and 0.98 for hyperglycaemia, respectively. CONCLUSIONS: There have been parallel increases in the rate of admissions due to dysglycaemia and the rate of antidiabetic prescriptions in England and Wales. Further analytical studies are required to investigate whether increased admission for dysglycaemia is associated with increased use of antidiabetic medications