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

Safety and Effectiveness of Direct Oral Anticoagulants Versus Warfarin in People with Atrial Fibrillation and Dementia

Objective: To determine risks of embolic events, bleeding, and mortality with direct oral anticoagulants (DOACs) vs warfarin in people with atrial fibrillation (AF) and dementia. / Design: New-user retrospective cohort study using The Health Improvement Network database. / Setting and Participants: A population-based sample comprising people with AF and dementia prescribed DOACs or warfarin from August 2011 to September 2017. / Methods: Risk of ischemic stroke (IS), ischemic stroke/transient ischemic attack/systemic embolism (IS/TIA/SE), all-cause mortality, intracranial bleeding (ICB), gastrointestinal bleeding (GIB), and other bleeding were compared for DOACs vs warfarin using propensity score–adjusted Poisson regression. Incidence rate ratios (IRRs) and absolute risk differences (ARDs) were calculated. / Results: Overall, 2399 people with AF and dementia initiated DOACs (42%) or warfarin (58%). Before propensity score adjustment, patients who initiated DOACs were older and had more comorbidities. After adjustment, DOAC initiators demonstrated similar risks of IS, TIA, or SE; IS alone; and other bleeding but reduced ICB risk (IRR 0.27, 95% CI 0.08, 0.86; ARD −5.2, 95% CI –6.5, −1.0, per 1000 person-years) compared with warfarin. Increased risk of GIB (IRR 2.11, 95% CI 1.30, 3.42; ARD 14.8, 95% CI 4.0, 32.4, per 1000 person-years) and all-cause mortality (IRR 2.06, 95% CI 1.60, 2.65; ARD 53.0, 95% CI 30.2, 82.8, per 1000 person-years) were observed in DOAC initiators compared with warfarin. / Conclusions and Implications: Among people with AF and dementia, initiating treatment with DOACs compared with warfarin was associated with similar risks of IS, TIA, or SE and IS alone. DOAC-treated patients demonstrated reduced ICB risk but increased GIB and all-cause mortality risks. We cannot exclude the possible impact of residual confounding from channeling of DOACs toward older and sicker people, particularly for the outcome of all-cause mortality. Further safety data are urgently needed to confirm findings

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

Trends in oral anticoagulant prescribing in individuals with type 2 diabetes mellitus: a population-based study in the UK

OBJECTIVE: To evaluate oral anticoagulant (OAC) prescribing trends in type 2 diabetes mellitus (T2DM) in the UK from 2001 to 2015. DESIGN: A cross-sectional drug utilisation study. SETTING: Electronic health records from The Health Improvement Network primary care database in the UK. PARTICIPANTS: Individuals with T2DM who received a record of OAC prescription. OUTCOME MEASURES: The prescribing trends of OAC medications in individuals with T2DM were examined from 2001 to 2015, stratified by age, gender and therapeutic classifications. RESULTS: A total of 361 635 individuals with T2DM were identified, of whom 36 570 were prescribed OAC from 2001 to 2015. The prevalence of OAC prescribing increased by 50.0%, from 1781 individuals receiving OAC prescriptions (IROACP) (4.4 (95% CI 4.2 to 4.6) per 100 persons) in 2001, to 17 070 IROACP (6.6 (95% CI 6.5 to 6.7) per 100 persons) in 2015. The prevalence of warfarin prescribing decreased by 14.0%, from 1761 individuals receiving warfarin prescriptions (IRWP) (98.9 (95% CI 98.4 to 99.4) per 100 persons) in 2001, to 14 533 IRWP (85.1 (95% CI 84.6 to 85.7) per 100 persons) in 2015. This corresponded with increased prescribing of direct oral anticoagulants (DOACs), from 18 individuals receiving DOAC prescriptions (IRDOACP) (0.1 (95% CI 0.08 to 0.23) per 100 persons) in 2010, to 3016 IRDOACP (17.6 (95% CI 17.1 to 18.2) per 100 persons) in 2015, during the same period. CONCLUSIONS: Prescribing of OACs in individuals with T2DM increased from 2001 to 2015. Since the introduction of DOACs, there has been a clear shift in prescribing towards these agents. Future studies are needed to assess the safety of coadministration of OAC medications and antidiabetic therapy with T2DM

Gastrointestinal bleeding risk with rivaroxaban vs aspirin in atrial fibrillation: a multinational study

Purpose: Comparative gastrointestinal bleeding (GIB) risk between rivaroxaban and low‐dose aspirin is unknown in patients with atrial fibrillation (AF). This study investigated GIB risk with rivaroxaban vs aspirin among two separate AF cohorts in Hong Kong and the United Kingdom, using a common protocol approach. Methods: This was a population‐based cohort study using separate data from the Clinical Data Analysis and Reporting System (CDARS) of the Hong Kong Hospital Authority (2010‐2018) and The Health Improvement Network (THIN) database in the United Kingdom (2011‐2017). Patients with AF newly prescribed aspirin or rivaroxaban were included. Cox proportional hazards regression was used to compare GIB risks for rivaroxaban vs aspirin, accounting for confounders using propensity score fine stratification approach. Results: In CDARS, 29 213 patients were included; n = 1052 (rivaroxaban), n = 28 161 (aspirin). Crude GIB event rates per 100 patient‐years in CDARS were 3.0 (aspirin) and 2.6 (rivaroxaban). No difference in GIB risk was observed between rivaroxaban and aspirin overall (HR = 1.04, 95%CI = 0.76‐1.42), and in dose‐stratified analyses (HR = 1.21, 95%CI = 0.84‐1.74 [20 mg/day]; HR = 0.80, 95%CI = 0.44‐1.45 [≤15 mg/day]). In THIN, 11 549 patients were included, n = 3496 (rivaroxaban) and n = 8053 (aspirin). Crude GIB event rates were 1.3 (aspirin) and 2.4 (rivaroxaban) per 100 patient‐years. No difference in GIB risk was observed between rivaroxaban and aspirin overall (HR = 1.40, 95%CI = 1.00‐1.98) and low‐dose rivaroxaban (≤15 mg/day) (HR = 1.00, 95%CI = 0.56‐1.30), but increased GIB risk was observed for rivaroxaban 20 mg/day vs aspirin (HR = 1.57, 95%CI = 1.08‐2.29). Conclusion: In patients with AF, GIB risk was comparable between aspirin and rivaroxaban ≤15 mg/day. GIB risk for rivaroxaban 20 mg/day vs aspirin remains uncertain and warrants further investigation

Incidence and prevalence of hypoglycaemia in type 1 and type 2 diabetes individuals: A systematic review and meta-analysis

BACKGROUND: Previous meta-analysis investigating the incidence and prevalence of hypoglycaemia in both types of diabetes is limited. The purpose of this review is to conduct a systematic review and meta-analysis of the existing literature which investigates the incidence and prevalence of hypoglycaemia in individuals with diabetes. METHODS: PubMed, Embase and Cochrane library databases were searched up to October 2018. Observational studies including individuals with diabetes of all ages and reporting incidence and/or prevalence of hypoglycaemia were included. Two reviewers independently screened articles, extracted data and assessed the quality of included studies. Meta-analysis was performed using a random effects model with 95% confidence interval (CI) to estimate the pooled incidence and prevalence of hypoglycaemia in individuals with diabetes. RESULTS: Our search strategy generated 35,007 articles, of which 72 studies matched the inclusion criteria and were included in the meta-analysis. The prevalence of hypoglycaemia ranged from 0.074% to 73.0%, comprising a total of 2,462,810 individuals with diabetes. The incidence rate of hypoglycaemia ranged from 0.072 to 42,890 episodes per 1,000 person-years: stratified by type of diabetes, it ranged from 14.5 to 42,890 episodes per 1,000 person-years and from 0.072 to 16,360 episodes per 1,000-person years in type 1 and type 2 diabetes, respectively. CONCLUSION: Hypoglycaemia is very common among individuals with diabetes. Further studies are needed to investigate hypoglycaemia-associated risk factors

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

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

A Systems-Based Analysis of Mono- and Combination Therapy for Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections

Antimicrobial resistance is a global threat. As “proof-of-concept, ” we employed a system-based approach to identify patient, bacterial, and drug variables contributing to mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKp) bloodstream infections exposed to colistin (COL) and ceftazidime-avibactam (CAZ/AVI) as mono- or combination therapies. Patients (n = 49) and CRKp isolates (n = 22) were part of the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-1), a multicenter, observational, prospective study of patients with carbapenem-resistant Enterobacterales (CRE) conducted between 2011 and 2016. Pharmacodynamic activity of mono- and combination drug concentrations was evaluated over 24 h using in vitro static time-kill assays. Bacterial growth and killing dynamics were estimated with a mechanism-based model. Random Forest was used to rank variables important for predicting