Debra A. Butt

The Risk of Hip Fracture After Initiating Antihypertensive Drugs in the Elderly

BACKGROUND Initiating antihypertensive drugs in the elderly has been associated with an immediate increased risk of falls. However, it is unknown whether initiation of antihypertensive drugs (eg, thiazide diuretics, angiotensin II converting-enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, or β-adrenergic blockers) is associated with an immediate increased risk of hip fractures. METHODS A population-based, self-controlled case series design using health care administrative databases identifying patients initiating an antihypertensive drug in Ontario, Canada. A cohort of newly treated hypertensive elderly patients was linked to the occurrence of hip fractures from April 1, 2000, to March 31, 2009, to create exposed cases. The risk period was the first 45 days following antihypertensive therapy initiation with control periods before and after treatment in a 450-day observation period. The outcome measure was the first occurrence for a proximal femoral fracture during the risk period. The analysis determined the relative incidence (incidence rate ratio), defined as the hip fracture rate in the risk period compared with control periods. RESULTS Among the 301,591 newly treated hypertensive community-dwelling elderly patients, 1463 hip fractures were identified during the observation period. Hypertensive elderly persons who began receiving an antihypertensive drug had a 43% increased risk of having a hip fracture during the first 45 days following treatment initiation relative to the control periods (incidence rate ratio, 1.43; 95% CI, 1.19-1.72). CONCLUSIONS Antihypertensive drugs were associated with an immediate increased hip fracture risk during the initiation of treatment in hypertensive community-dwelling elderly patients. Caution is advised when initiating antihypertensive drugs in the elderly.

Gabapentin for the treatment of menopausal hot flashes: a randomized controlled trial.

Objective: To compare the effectiveness and tolerability of gabapentin with placebo for the treatment of hot flashes in women who enter menopause naturally. Design: A randomized, double-blind, placebo-controlled trial was conducted across the greater Toronto area between March 2004 and April 2006 in the community and primary care settings. Eligible participants were 200 women in natural menopause, aged 45 to 65 years, having at least 14 hot flashes per week. Study participants were randomized to receive gabapentin 300 mg oral capsules or placebo three times daily for 4 weeks. The primary outcome measure was the mean percentage change from baseline to week 4 in daily hot flash score, determined from participant diaries. Secondary outcome measures included changes in weekly mean hot flash scores and frequencies, quality of life, and adverse events. Results: Of the 197 participants, 193 (98%) completed the study. Analysis was by intention to treat. Hot flash scores decreased by 51% (95% CI: 43%-58%) in the gabapentin group, compared with 26% (95% CI: 18%-35%) on placebo, from baseline to week 4. This twofold improvement was statistically significant (P < 0.001). The Menopause-Specific Quality-of-Life vasomotor score decreased by 1.7 (95% CI: 1.3-2.1; P < 0.001) in the gabapentin group. These women reported greater dizziness (18%), unsteadiness (14%), and drowsiness (12%) at week 1 compared with those taking placebo; however, these symptoms improved by week 2 and returned to baseline levels by week 4. Conclusions: Gabapentin at 900 mg/day is an effective and well-tolerated treatment for hot flashes.

Assessing the validity of using administrative data to identify patients with epilepsy

Previous validation studies assessing the use of administrative data to identify patients with epilepsy have used targeted sampling or have used a reference standard of patients in the neurologist, hospital, or emergency room setting. Therefore, the validity of using administrative data to identify patients with epilepsy in the general population has not been previously assessed. The purpose of this study was to determine the validity of using administrative data to identify patients with epilepsy in the general population.

Validity of Administrative Data for Identifying Patients Who Have Had a Stroke or Transient Ischemic Attack Using EMRALD as a Reference Standard

BACKGROUND Surveillance for stroke/transient ischemic attack (TIA) using administrative data has traditionally been limited to reporting patients who had an acute event and were hospitalized. This underestimates the true prevalence because many events do not result in hospitalization. We examined whether the accuracy of administrative data for identifying prevalent stroke/TIA could be improved by using data from both inpatient and outpatient visits. METHODS An administrative data validation reference standard was developed through chart abstraction of 5000 adult patients randomly sampled from 73,014 patients of 83 family physicians who participate in the Electronic Medical Record Administrative Data Linked Database (EMRALD), in Ontario, Canada. RESULTS The prevalence of stroke/TIA in our adult population was 3.0%. An algorithm of 1 hospital record had a sensitivity of 35.3% (27.7%-43.0%) and specificity of 99.8% (99.7%-99.9%), whereas an algorithm of 2 physician billings within 1 year or 1 hospitalization had a sensitivity of 68.0% (95% confidence interval [CI], 60.5%-75.5%) and specificity of 98.9% (95% CI, 98.6%-99.2%) for the identification of patients who had ever had a stroke/TIA. We found that hospitalization data underestimated the prevalence of stroke by > 50% and TIA by > 66% compared with using both hospitalization and physician claims data. CONCLUSIONS The use of outpatient physician claims data in addition to hospitalization data improves the sensitivity of administrative data for the identification of prevalent stroke/TIA and may be used to estimate the prevalence of cerebrovascular events in large populations and over time.

Minimal decrease in hot flashes desired by postmenopausal women in family practice.

Objective: To determine the minimal important difference in the frequency and severity of hot flashes that postmenopausal women desire from a nonhormonal agent. Design: Women recorded their number of hot flashes daily, along with their degree of severity, using a diary for 1 week and completed the Menopause-Specific Quality of Life Questionnaire. Women were asked to report the percentage reduction in hot flashes that they would find clinically important. Distribution-based estimates were used to estimate the minimal important difference. Results: Approximately 69% of the postmenopausal women who reported their hot flashes as moderate to severe responded that they wanted a nonhormonal agent that provided at least a 50% mean reduction in the frequency of hot flashes (95% CI, 32% to 66%). Median hot flash reduction for all respondents was 50%. Conclusions: The minimal clinically important difference in hot flashes is approximately 50%. This estimate can provide the basis to calculate sample size in clinical trials of anti-hot flash agents and in selecting possible candidates for investigation.

Development and validation of an administrative data algorithm to estimate the disease burden and epidemiology of multiple sclerosis in Ontario, Canada

Background: Few studies have assessed the accuracy of administrative data for identifying multiple sclerosis (MS) patients. Objectives: To validate administrative data algorithms for MS, and describe the burden and epidemiology over time in Ontario, Canada. Methods: We employed a validated search strategy to identify all MS patients within electronic medical records, to identify patients with and without MS (reference standard). We then developed and validated different combinations of administrative data for algorithms. The most accurate algorithm was used to estimate the burden and epidemiology of MS over time. Results: The accuracy of the algorithm of one hospitalisation or five physician billings over 2 years provided both high sensitivity (84%) and positive predictive value (86%). Application of this algorithm to provincial data demonstrated an increasing cumulative burden of MS, from 13,326 patients (0.14%) in 2000 to 24,647 patients in 2010 (0.22%). Age-and-sex standardised prevalence increased from 133.9 to 207.3 MS patients per 100,000 persons in the population, from 2000 – 2010. During this same period, age-and-sex-standardised incidence varied from 17.9 to 19.4 patients per 100,000 persons. Conclusions: MS patients can be accurately identified from administrative data. Our findings illustrated a rising prevalence of MS over time. MS incidence rates also appear to be rising since 2009.

The Rising Burden of Rheumatoid Arthritis Surpasses Rheumatology Supply in Ontario

ObjectivesAccurate data on the burden of rheumatoid arthritis (RA) are scarce, but critical in helping health care providers and decision makers to optimize clinical and public health strategies for disease management. We quantified the burden of RA in Ontario from 1996 to 2010 by age, sex and health planning region.MethodsWe used the Ontario Rheumatoid Arthritis administrative Database (ORAD), a validated population-based cohort of all Ontarians with RA, to estimate the crude prevalence and incidence of RA among men and women, and by age group from 1996 to 2010. Burden by area of patient residence and rheumatology supply also were determined.ResultsThe number of RA patients increased over time, from 42,734 Ontarians (0.5%) in 1996 to 97,499 (0.9%) in 2010. On average 5,830 new RA patients were diagnosed each year. In 2010, the burden was higher among females (1.3%) than males (0.5%) and increased with age, with almost half of all RA patients aged 65 years and older. The burden was higher in northern communities (1.0%) than in southern urban areas (0.7%). During the study period, the number of rheumatologists practicing in Ontario remained unchanged (approximately 160).ConclusionOver a 15-year period, the number of RA patients more than doubled with no concomitant increase in the number of practicing rheumatologists. We observed considerable regional variation in burden, with the highest rates observed in the north. Our findings highlight the need for regional approaches to the planning and delivery of RA care in order to manage the growing burden.RésuméObjectifsLes données précises sur le fardeau de la polyarthrite rhumatoïde (PR) sont rares mais essentielles pour aider le personnel soignant et les décideurs à optimiser les stratégies cliniques et de santé publique en gestion des soins thérapeutiques. Nous avons chiffré le fardeau de la PR en Ontario de 1996 à 2010 selon l’âge, le sexe et la région de planification sanitaire.MéthodeNous avons utilisé la base de données administratives sur la polyarthrite rhumatoïde de l’Ontario (ORAD), une cohorte populationnelle validée de tous les Ontariens atteints de PR, pour estimer la prévalence et l’incidence brutes de la PR selon le sexe et le groupe d’âge de 1996 à 2010. Nous avons aussi déterminé le fardeau de la maladie selon la région de résidence des patients et l’offre en rhumatologie.RésultatsLe nombre de patients atteints de PR a augmenté avec le temps, passant de 42 734 Ontariens (0,5%) en 1996 à 97 499 (0,9%) en 2010. En moyenne, 5 830 nouveaux patients par année ont reçu un diagnostic de PR. En 2010, le fardeau était plus lourd chez les femmes (1,3%) que chez les hommes (0,5%), et il augmentait avec l’âge: près de la moitié des patients atteints de PR avaient 65 ans et plus. Le fardeau était plus lourd dans les communautés nordiques (1,0%) que dans les agglomérations urbaines du Sud (0,7%). Sur la période de l’étude, le nombre de rhumatologues exerçant en Ontario est resté inchangé (environ 160).ConclusionSur une période de 15 ans, le nombre de patients atteints de PR a plus que doublé, sans augmentation comparable du nombre de rhumatologues en exercice. Nous avons relevé des écarts régionaux considérables dans le fardeau de la maladie, les plus hauts taux étant observés dans le Nord. Nos constatations soulignent le besoin d’approches régionales en matière de planification et de prestation des soins de la PR afin de composer avec l’alourdissement du fardeau.

Benefits and risks of antihypertensive medications in the elderly

Hypertension is highly prevalent in older age and accounts for a large proportion of cardiovascular (CV) morbidity and mortality worldwide. Isolated systolic hypertension is more common in the elderly than younger adults and associated with poor outcomes such as cerebrovascular disease and acute coronary events. International guidelines are inconsistent in providing recommendations on optimal blood pressure targets in hypertensive elderly patients as a result of the limited evidence in this population. Evidence from clinical trials supports the use of antihypertensive drugs in hypertensive elderly patients due to benefits in reducing CV disease and mortality. However, elderly participants in these trials may not be typical of elderly patients seen in routine clinical practice, and the potential risks associated with use of antihypertensive drugs in the elderly are not as well studied as younger participants. Therefore, the purpose of this review was to provide a comprehensive summary of the benefits and risks of the use of antihypertensive drugs in elderly patients (aged ≥65 years), highlighting landmark clinical trials and observational studies. We will focus on specific outcomes relating to the benefits and risks of these medications in hypertensive elderly patients, such as CV disease, cognitive decline, dementia, orthostatic hypotension, falls, fractures, cancer and diabetes, in order to provide an update of the most relevant and current evidence to help inform clinical decision‐making.

Risk of Osteoporotic Fractures With Angiotensin II Receptor Blockers Versus Angiotensin-Converting Enzyme Inhibitors in Hypertensive Community-Dwelling Elderly

Angiotensin‐converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) are used to treat hypertension; however, in vivo and clinical studies suggest that ARBs and ACE inhibitors may exert different effects on bone. The association between long‐term use of ARBs and ACE inhibitors and fracture requiring medical attention is limited. We conducted a population‐based, retrospective cohort study with propensity score matching using administrative databases in Ontario, Canada, to examine the risk of osteoporosis‐related fractures in hypertensive elderly treated with ARBs versus ACE inhibitors. We identified a cohort of newly treated hypertensive patients aged 66 years and older who initiated an ACE inhibitor from May 1, 2004, to March 31, 2012, and matched them to ARB users on propensity score, sex, and age at drug initiation. The primary outcome was hip fracture, and secondary outcomes were non‐hip major osteoporotic fractures (other femoral, clinical vertebral, forearm, wrist, humerus) and other osteoporotic fractures (pelvis, clavicle, patella, shoulder, upper arm, tibia, fibula, ankle, scapula, ribs, sternum, trunk). We calculated hazard ratios (HRs) using Cox proportional hazards model with robust standard errors. Of the 87,635 patients who initiated treatment, 28,819 (32.9%) started ARBs and 58,816 (67.1%) started ACE inhibitors. Among new ARB users, 27,815 (96.5%) were successfully matched to ACE inhibitor users. Without dose adjustment, no significant association was observed for ARBs relative to ACE inhibitor users for hip fractures (HR = 0.88; 95% confidence interval [CI] 0.70–1.11), with a decreased risk of other major osteoporotic fractures (HR = 0.81; CI 0.70–0.93) and no significant association for other osteoporotic fractures (HR = 0.88; CI 0.74–1.05). When adjusted for dosage, there was no significant difference between the effects of ARBs and ACE inhibitors on hip (HR = 0.99; CI 0.78–1.25), other major osteoporotic (HR = 0.87; CI 0.75–1.01), and other osteoporotic fractures (HR = 0.90; CI 0.74–1.08).

Antihypertensive Drug Prescribing and Persistence Among New Elderly Users: Implications for Persistence Improvement Interventions

BACKGROUND The objective of this study was to examine persistence rates and factors influencing persistence for new elderly users of antihypertensive drugs. METHODS We conducted a population-based cohort study in Ontario of adults aged 66 years or older to identify new users of antihypertensive medications between 1999 and 2010. Two-year therapy and class persistence were defined as persistence on any antihypertensive medication and persistence only on the same antihypertensive medication class, respectively. RESULTS From 1999-2010, the prevalence of antihypertensive drug use increased from 47.8%-60.5% (P < 0.0001). Persistence was evaluated in 420,148 new users of antihypertensive drugs. After 2 years, therapy persistence was 58.9% and varied according to initial class prescribed, from 52.3% for diuretics to 64.1% for angiotensin-converting enzyme inhibitors. Class persistence ranged from 25.3% for diuretics to 35.8% for angiotensin II receptor blockers. Therapy persistence rates were greater in new users from more recent years (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.21-1.27). Subgroups that demonstrated poorer persistence included patients older than 75 years (aOR, 0.95; 95% CI, 0.94-0.96), those with lowest neighbourhood income quintile (aOR, 0.81; 95% CI, 0.80-0.83 compared with the highest quintile), those from urban vs rural areas (aOR, 0.83; 95% CI, 0.81-0.84), and those who started on diuretics as initial monotherapy compared with all other drug classes. CONCLUSIONS Although 2-year therapy and class persistence were low for new users of antihypertensive drugs, improvements have occurred over the past decade. Our data highlight subgroups to target for future persistence improvement interventions.