Persistence and adherence to parenteral osteoporosis therapies: a systematic review.

Osteoporosis is a chronic disease of low bone mass and fragility. Treatment is frequently compromised by suboptimal medication compliance causing increased morbidity. This review investigates adherence and persistence to parenteral osteoporosis therapies. Findings reveal parenteral medications requiring reduced dosing frequency have higher compliance than oral therapies. This systematic review examines real-world adherence to parenteral osteoporosis therapies. We searched PubMed, Medline, and EMBASE databases for English language observational studies that examined patient adherence and/or persistence to parenteral osteoporosis treatments (teriparatide sc, ibandronate iv, zoledronic acid iv, and denosumab sc) in adults with osteoporosis published up to September 2018. Studies with only self-reported adherence or persistence data and those with less than 20 patients were excluded. Quality assessment of included studies was completed using the Newcastle-Ottawa quality assessment scale (NOS). We identified 40 eligible studies. Teriparatide was examined in 29 studies, with persistence rates of 10-87% (median 55%) at 1 year and 10-69% (median 29.5%) at 2 years, and adherence rates of 21-89% (median 53%) at 1 year and 37-68% (median 40%) at 2 years. Ten studies of zoledronic acid reported persistence rates of 34-73% (median 42%) for second dose and 20-54% (median 35.8%) for third dose. Ten studies of ibandronate adherence reported and 2-year persistence rates of 31-58% (median 47.5%) in 1 year and 13-35% (median 25%) at 2 years, and adherence rates of 21-72% (median 47.3%) and 15-58% (median 36.5%) respectively. Denosumab was reported in 19 studies, with second (1 year) and fourth (2 year) dose persistence rates of 61-100% (median 81%) and 36-99% (median 45.5%). There is substantial heterogeneity in reports of persistence and adherence rates with parenteral osteoporosis therapies. Most of the published data are from short-term studies and evaluations of long-term adherence and persistence with parenteral therapies for osteoporosis are needed.

A comparison of four risk models for the prediction of cardiovascular complications in patients with a history of atrial fibrillation undergoing non-cardiac surgery.

It is unclear how best to predict peri-operative cardiovascular risk in patients with atrial fibrillation undergoing non-cardiac surgery. This study examined the accuracy of the revised cardiac risk index and three atrial fibrillation thrombo-embolic risk models for predicting 30-day cardiovascular events after non-cardiac surgery in patients with a pre-operative history of atrial fibrillation. We conducted a prospective cohort study in 28 centres from 2007 to 2013 of 40,004 patients ≥ 45 years of age undergoing inpatient non-cardiac surgery who were followed until 30 days after surgery for cardiovascular events (defined as myocardial injury, heart failure, stroke, resuscitated cardiac arrest or cardiovascular death). The 2088 patients with a pre-operative history of atrial fibrillation were at higher risk of peri-operative cardiovascular events compared with the 34,830 patients without a history of atrial fibrillation (29% vs. 13%, respectively, adjusted odds ratio 1.30 (95%CI 1.17-1.45). Compared with the revised cardiac risk index (c-index 0.60), all atrial fibrillation thrombo-embolic risk scores were significantly better at predicting peri-operative cardiovascular events: CHADS2 (c-index 0.62); CHA2 DS2 -VASc (c-index 0.63); and R2 CHADS2 (c-index 0.65), respectively. Although the three thrombo-embolic risk prediction models were significantly better than the revised cardiac risk index for prediction of peri-operative cardiovascular events, none of the four models exhibited strong discrimination metrics. There remains a need to develop a better peri-operative risk prediction model.

The hospital frailty risk score in patients with heart failure is strongly associated with outcomes but less so with pharmacotherapy.

BACKGROUND: Although frailty is known to be an important prognostic factor in heart failure (HF), HF risk-adjustment models do not incorporate frailty measures and the interplay between frailty, age and pharmacotherapy is unclear. OBJECTIVES: To explore the relationships between frailty, pharmacotherapy and outcomes in heart failure (HF). METHODS: Retrospective cohort study of all adults in Alberta, Canada hospitalized for the first time for HF between 2004 and 2016. Frailty was defined using the Hospital Frailty Risk Score (HFRS). RESULTS: In 26 626 patients (mean age 77.4 years), the 8887 (33.4%) defined as frail (HFRS ≥ 5) were older, had higher Charlson scores and more prior emergency department visits or hospitalizations. The HFRS and the Charlson Score were only weakly correlated (r = 0.35). Whilst more common in older patients (41.4% of patients 80 or older), frailty was present in 22.4% of patients younger than 65. Frail patients had longer lengths of stay and worse outcomes postdischarge, but adding the HFRS to age, sex and Charlson score did not improve prediction of events (c-statistics 0.69 for 30-day mortality after admission, and 0.54 for 30-day readmission/ED visit/or death after discharge). Frail patients younger than 65 were significantly more likely than nonfrail patients 80 or older to be prescribed high-dose evidence-based HF therapies (27.1% vs. 22.2%, P = 0.003). CONCLUSION: Although the HFRS reflects aspects of frailty that patient age and Charlson scores do not, the addition of the HFRS to standard risk prediction equations provides little additional information. Prescribing practices correlate more with patient age than frailty status.

Adherence to osteoporosis therapy after an upper extremity fracture: a pre-specified substudy of the C-STOP randomized controlled trial.

Despite their proven efficacy for secondary fracture prevention, long-term adherence with oral bisphosphonates is poor. INTRODUCTION: To compare the effectiveness of two interventions on long-term oral bisphosphonate adherence after an upper extremity fragility fracture. METHODS: Community-dwelling participants 50 years or older with upper extremity fragility fractures not previously treated with bisphosphonates were randomized to either a multi-faceted patient and physician educational intervention (the active control arm) vs. a nurse-led case manager (the study arm). Primary outcome was adherence (taking > 80% of prescribed doses) with prescribed oral bisphosphonates at 12 months postfracture between groups; secondary outcomes included rates of primary non-adherence and 24-month adherence. We also compared quality of life between adherent and non-adherent patients. RESULTS: By 12 months, adherence with the initially prescribed bisphosphonate was similar (p = 0.96) in both groups: 38/48 (79.2%) in the educational intervention group vs. 66/83 (79.5%) in the case manager arm. By 24 months, adherence rates were 67% (32/48) in the educational intervention group vs. 53% (43/81) in case managed patients (p = 0.13). Primary non-adherence was 6% (11 patients) in the educational intervention group and 12% (21 patients) in the case managed group (p = 0.07). Prior family history of osteoporosis (aOR 2.1, 95% CI 1.0 to 4.4) and being satisfied with current medical care (aOR 2.3, 95% CI 1.1 to 4.8) were associated with better adherence while lower income (aOR 0.2, 95% CI 0.1 to 0.6, for patients with income < $30,000 per annum) was associated with poorer rates of adherence. There were no differences in health-related quality of life scores at baseline or during follow-up between patients who were adherent and those who were not. CONCLUSION: While both interventions achieved higher oral bisphosphonate adherence compared to previously reported adherence rates in the general population, primary non-adherence and long-term adherence to bisphosphonates were similar in both arms. Adherence was influenced by family history of osteoporosis, satisfaction with current medical care, and income. TRIAL REGISTRATION: ClinicalTrials.gov : NCT01401556.

Understanding fragility fracture patients' decision-making process regarding bisphosphonate treatment.

We aimed to understand how patients 50 years and older decided to persist with or stop osteoporosis (OP) treatment. Processes related to persisting with or stopping OP treatments are complex and dynamic. The severity and risks and harms related to untreated clinical OP and the favorable benefit-to-risk profile for OP treatments should be reinforced. INTRODUCTION: Older adults with fragility fracture and clinical OP are at high risk of recurrent fracture, and treatment reduces this risk by 50 %. However, only 20 % of fracture patients are treated for OP and half stop treatment within 1 year. We aimed to understand how older patients with new fractures decided to persist with or stop OP treatment over 1 year. METHODS: We conducted a grounded theory study of patients 50 years and older with upper extremity fracture who started bisphosphonates and then reported persisting with or stopping treatment at 1 year. We used theoretical sampling to identify patients who could inform emerging concepts until data saturation was achieved and analyzed these data using constant comparison. RESULTS: We conducted 21 interviews with 12 patients. Three major themes emerged. First, patients perceived OP was not a serious health condition and considered its impact negligible. Second, persisters and stoppers differed in weighting the risks vs benefits of treatments, where persisters perceived less risk and more benefit. Persisters considered treatment "required" while stoppers often deemed treatment "optional." Third, patients could change treatment status even 1-year post-fracture because they re-evaluated severity and impact of OP vs risks and benefits of treatments over time. CONCLUSIONS: The processes and reasoning related to persisting with or stopping OP treatments post-fracture are complex and dynamic. Our findings suggest two areas of leverage for healthcare providers to reinforce to improve persistence: (1) the severity and risks and harms related to untreated clinical OP and (2) the favorable benefit-to-risk profile for OP treatments.

Risk of new-onset heart failure in patients using sitagliptin: a population-based cohort study.

AIMS: To examine whether patients using sitagliptin at the time of an acute coronary syndrome event are at increased risk of incident heart failure compared with those not exposed. METHODS: Using US claims data, people with diabetes without a history of heart failure in the 3 years before hospitalization for acute coronary syndrome were identified for the period 2004 to 2010. We used a nested case-control design, whereby cases were patients who developed incident heart failure <30 days after admission to hospital for acute coronary syndrome and were matched by age and sex with up to 10 controls with no heart failure. Subjects exposed or not exposed to sitagliptin in the 90 days before acute coronary syndrome admission were compared using conditional logistic regression after adjustment for clinical and laboratory data, healthcare utilization and propensity scores. RESULTS: In total, 457 cases of heart failure developing de novo after diagnosis of acute coronary syndrome were matched to 4570 controls. The average age of the subjects was 55 years and 65% were male. Overall, 11 of 147 (7%) people exposed to sitagliptin developed heart failure compared with 446 of the 4880 people not exposed (9%, adjusted odds ratio 0.75, 95% CI 0.38-1.46; P=0.40). Sitagliptin exposure before acute coronary syndrome was not associated with an increased risk of death or heart failure combined (7% vs 9%, adjusted odds ratio 0.66, 95% CI 0.34-1.28). CONCLUSIONS: In our sample of patients who are at high risk of heart failure after acute coronary syndrome, sitagliptin exposure was not associated with an increased risk of de novo heart failure.

Prognostic significance of anaemia in patients with heart failure with preserved and reduced ejection fraction: results from the MAGGIC individual patient data meta-analysis.

BACKGROUND: Anaemia is common among patients with heart failure (HF) and is an important prognostic marker. AIM: We sought to determine the prognostic importance of anaemia in a large multinational pooled dataset of prospectively enrolled HF patients, with the specific aim to determine the prognostic role of anaemia in HF with preserved and reduced ejection fraction (HF-PEF and HF-REF, respectively). DESIGN: Individual person data meta-analysis. METHODS: Patients with haemoglobin (Hb) data from the MAGGIC dataset were used. Anaemia was defined as Hb < 120 g/l in women and <130 g/l in men. HF-PEF was defined as EF ≥ 50%; HF-REF was EF < 50%. Cox proportional hazard modelling, with adjustment for clinically relevant variables, was undertaken to investigate factors associated with 3-year all-cause mortality. RESULTS: Thirteen thousand two hundred and ninety-five patients with HF from 19 studies (9887 with HF-REF and 3408 with HF-PEF). The prevalence of anaemia was similar among those with HF-REF and HF-PEF (42.8 and 41.6% respectively). Compared with patients with normal Hb values, those with anaemia were older, were more likely to have diabetes, ischaemic aetiology, New York Heart Association class IV symptoms, lower estimated glomerular filtration rate and were more likely to be taking diuretic and less likely to be taking a beta-blocker. Patients with anaemia had higher all-cause mortality (adjusted hazard ratio [aHR] 1.38, 95% confidence interval [CI] 1.25-1.51), independent of EF group: aHR 1.67 (1.39-1.99) in HF-PEF and aHR 2.49 (2.13-2.90) in HF-REF. CONCLUSIONS: Anaemia is an adverse prognostic factor in HF irrespective of EF. The prognostic importance of anaemia was greatest in patients with HF-REF.

The prediction of postoperative stroke or death in patients with preoperative atrial fibrillation undergoing non-cardiac surgery: a VISION sub-study.

BACKGROUND: The optimal means of pre-operative risk stratification in patients with atrial fibrillation (AF) is uncertain. OBJECTIVE: To examine the accuracy of AF thromboembolic risk models (the CHADS2, CHA2DS2-VASc, and R2CHADS2 scores) for predicting 30-day stroke and/or all-cause mortality after non-cardiac surgery in patients with preoperative AF, and to compare these risk scores with the Revised Cardiac Risk Index (RCRI). PATIENTS/METHODS: A multicentre (8 countries, 2007-2011) prospective cohort study of patients ≥ 45 years of age undergoing inpatient non-cardiac surgery, who were followed until 30 days after surgery. We calculated c-statistics for each risk prediction model and net reclassification improvements (NRIs) compared with the RCRI. RESULTS: The 961 patients with preoperative AF were at higher risk of any cardiovascular event in the 30 days postoperatively compared with the 13 001 patients without AF: 26.6% vs. 9.0%; adjusted odds ratio, 1.58; 95% confidence interval [CI], 1.33-1.88. All thromboembolic risk scores predicted postoperative death just as well as the RCRI (with c-indices between 0.67 and 0.72). Compared with the RCRI (which had a c-index of 0.64 for 30-day stroke/death), the CHADS2 (c-index, 0.67; NRI, 0.31; 95% CI, 0.02-0.61) significantly improved postoperative stroke/mortality risk prediction, largely due to improved discrimination of patients who did not subsequently have an event. CONCLUSIONS: In AF patients, the three thromboembolic risk scores performed similarly to the RCRI in predicting death within 30 days and the CHADS2 score was the best predictor of postoperative stroke/death regardless of type of surgery.

The impact of multimorbidity on short-term events in patients with community-acquired pneumonia: prospective cohort study.

The impact of multimorbidity on patients with community-acquired pneumonia has not been well characterised. Thus, our aim was to explore the relationship between multimorbidity and adverse events within 90 days of discharge. Data were prospectively collected for a population-based cohort of all adults discharged from any of the seven emergency departments (ED) or six hospitals in Edmonton (Alberta, Canada) with community-acquired pneumonia. Multivariable Cox regression models were used to examine the independent association between multimorbidity (defined as two or more chronic conditions) and subsequent 90-day mortality, hospitalisation, or ED visits after treatment of pneumonia. The cohort included 5565 patients, mean age was 57 years (SD 20), 54% were male, and 59% were treated as outpatients; 1602 (29%) patients had multimorbidity. Within 90 days, 255 (5%) patients died, 1205 (22%) were hospitalised, 1280 (23%) died or were hospitalised, and 2049 (37%) were admitted to the ED. The presence of multimorbidity was independently associated with an increased risk of death or hospitalisation within 90 days (37% vs. 17% for those without multimorbidity, adjusted hazard ratio: 1.43, 95% confidence interval: 1.26 to 1.62) as well as ED visits (45% vs. 34%, adjusted hazard ratio: 1.40, 95% confidence interval: 1.26 to 1.56). Multimorbidity was present in one-third of all patients with pneumonia in our study, and it was independently associated with death, hospitalisation, or return to ED within 90 days of discharge. Our findings suggest that multimorbidity is strongly related to prognosis and should be considered when making site-of-care decisions in the ED or deciding upon readiness for discharge.

Intraclass differences among antihypertensive drugs.

The four major classes of antihypertensive drugs­diuretics, ß-blockers, calcium channel blockers, and renin-angiotensin system inhibitors (including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers)­have significant qualitative and quantitative differences in the adverse effects they cause. Structural and chemical differences have been identified within these classes, especially among the calcium channel blockers and, to a lesser extent, among the thiazide/thiazide-like diuretics. However, it has been more difficult to demonstrate that these differences translate into differential effects with respect to either the surrogate endpoint of blood pressure reduction or, more importantly, hypertension-related cardiovascular complications. Based on a hierarchy-of-evidence approach, differences are apparent between hydrochlorothiazide and chlorthalidone based on evidence of moderate quality. Low-quality evidence suggests atenolol is less effective than other ß-blockers. However, no significant intraclass differences have been established among the other classes of antihypertensive drugs.

Critical impact of patient knowledge and bone density testing on starting osteoporosis treatment after fragility fracture: secondary analyses from two controlled trials.

UNLABELLED: Most patients are not treated for osteoporosis after their fragility fracture "teachable moment." Among almost 400 consecutive wrist fracture patients, we determined that better-than-average osteoporosis knowledge (adjusted odds = 2.6) and BMD testing (adjusted odds = 6.5) were significant modifiable facilitators of bisphosphonate treatment while male sex, working outside the home, and depression were major barriers. INTRODUCTION: In the year following fragility fracture, fewer than one quarter of patients are treated for osteoporosis. Although much is known regarding health system and provider barriers and facilitators to osteoporosis treatment, much less is understood about modifiable patient-related factors. METHODS: Older patients with wrist fracture not treated for osteoporosis were enrolled in trials that compared a multifaceted intervention with usual care controls. Baseline data included a test of patient osteoporosis knowledge. We then determined baseline factors that independently predicted starting bisphosphonate treatment within 1 year. RESULTS: Three hundred seventy-four patients were enrolled; mean age 64 years, 78 % women, 90 % white, and 54 % with prior fracture. Within 1 year, 86 of 374 (23 %) patients were treated with bisphosphonates. Patients who were treated had better osteoporosis knowledge at baseline (70 % correct vs 57 % for untreated, p < 0.001) than patients who remained untreated; conversely, untreated patients were more likely to be male, still working, and report depression. In fully adjusted models, osteoporosis knowledge was independently associated with starting bisphosphonates (adjusted OR 2.6, 95 %CI 1.3-5.3). Obtaining a BMD test (aOR 6.5, 95 %CI 3.4-12.2) and abnormal BMD results (aOR 34.5, 95 %CI 16.8-70.9) were strongly associated with starting treatment. CONCLUSIONS: The most important modifiable facilitators of osteoporosis treatment in patients with fracture were knowledge and BMD testing. Specifically targeting these two patient-level factors should improve post-fracture treatment rates.

The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data.

BACKGROUND: In heart failure (HF), obesity, defined as body mass index (BMI) ≥30 kg m(-2), is paradoxically associated with higher survival rates compared with normal-weight patients (the 'obesity paradox'). We sought to determine if the obesity paradox differed by HF subtype (reduced ejection fraction (HF-REF) versus preserved ejection fraction (HF-PEF)). PATIENTS AND METHODS: A sub-analysis of the MAGGIC meta-analysis of patient-level data from 14 HF studies was performed. Subjects were divided into five BMI groups: <22.5, 22.5-24.9 (referent), 25-29.9, 30-34.9 and ≥35 kg m(-2). Cox proportional hazards models adjusted for age, sex, aetiology (ischaemic or non-ischaemic), hypertension, diabetes and baseline blood pressure, stratified by study, were used to examine the independent association between BMI and 3-year total mortality. Analyses were conducted for the overall group and within HF-REF and HF-PEF groups. RESULTS: BMI data were available for 23 967 subjects (mean age, 66.8 years; 32% women; 46% NYHA Class II; 50% Class III) and 5609 (23%) died by 3 years. Obese patients were younger, more likely to receive cardiovascular (CV) drug treatment, and had higher comorbidity burdens. Compared with BMI levels between 22.5 and 24.9 kg m(-2), the adjusted relative hazards for 3-year mortality in subjects with HF-REF were: hazard ratios (HR)=1.31 (95% confidence interval=1.15-1.50) for BMI <22.5, 0.85 (0.76-0.96) for BMI 25.0-29.9, 0.64 (0.55-0.74) for BMI 30.0-34.9 and 0.95 (0.78-1.15) for BMI ≥35. Corresponding adjusted HRs for those with HF-PEF were: 1.12 (95% confidence interval=0.80-1.57) for BMI <22.5, 0.74 (0.56-0.97) for BMI 25.0-29.9, 0.64 (0.46-0.88) for BMI 30.0-34.9 and 0.71 (0.49-1.05) for BMI ≥35. CONCLUSIONS: In patients with chronic HF, the obesity paradox was present in both those with reduced and preserved ventricular systolic function. Mortality in both HF subtypes was U-shaped, with a nadir at 30.0-34.9 kg m(-2).

Are users of sulphonylureas at the time of an acute coronary syndrome at risk of poorer outcomes?

AIMS: Adenosine triphosphate sensitive potassium (K(ATP)) channel activity is cardioprotective during ischaemia. One of the purported mechanisms for sulphonylurea adverse effects is through inhibition of these channels. The purpose of this study is to examine whether patients using K(ATP) channel inhibitors at the time of an acute coronary syndrome are at greater risk of death or heart failure (HF) than those not exposed. METHODS: Using linked administrative databases we identified all adults who had an acute coronary syndrome between April 2002 and October 2006 (n = 21 023). RESULTS: Within 30 days of acute coronary syndrome, 5.3% of our cohort died and 15.6% were diagnosed with HF. Individuals with diabetes exhibited significantly higher risk of death (adjusted OR: 1.20, 95% CI: 1.03-1.40) and death or HF (aOR: 1.73, 95% CI: 1.59-1.89) than individuals without diabetes. However, there was no significantly increased risk of death (aOR: 1.00, 95% CI: 0.76-1.33) or death/HF (aOR: 1.06, 95% CI: 0.89-1.26) in patients exposed to K(ATP) channel inhibitors versus patients not exposed to K(ATP) channel inhibitors prior to their acute coronary syndrome. CONCLUSIONS: Diabetes is associated with an increased risk of death or HF within 30 days of an acute coronary syndrome. However, we did not find any excess risk of death or HF associated with use of K(ATP) channel inhibitors at the time of an acute coronary syndrome, raising doubts about the hypothesis that sulphonylureas inhibit the cardioprotective effects of myocardial K(ATP) channels.

Comparative safety and effectiveness of sitagliptin in patients with type 2 diabetes: retrospective population based cohort study.

OBJECTIVE: To determine if the use of sitagliptin in newly treated patients with type 2 diabetes is associated with any changes in clinical outcomes. DESIGN: Retrospective population based cohort study. SETTING: Large national commercially insured US claims and integrated laboratory database. PARTICIPANTS: Inception cohort of new users of oral antidiabetic drugs between 2004 and 2009 followed until death, termination of medical insurance, or December 31 2010. MAIN OUTCOME MEASURE: Composite endpoint of all cause hospital admission and all cause mortality, assessed with time varying Cox proportional hazards regression after adjustment for demographics, clinical and laboratory data, pharmacy claims data, healthcare use, and time varying propensity scores. RESULTS: The cohort included 72,738 new users of oral antidiabetic drugs (8032 (11%) used sitagliptin; 7293 (91%) were taking it in combination with other agents) followed for a total of 182,409 patient years. The mean age was 52 (SD 9) years, 54% (39,573) were men, 11% (8111) had ischemic heart disease, and 9% (6378) had diabetes related complications at the time their first antidiabetic drug was prescribed. 14,215 (20%) patients met the combined endpoint. Sitagliptin users showed similar rates of all cause hospital admission or mortality to patients not using sitagliptin (adjusted hazard ratio 0.98, 95% confidence interval 0.91 to 1.06), including patients with a history of ischemic heart disease (adjusted hazard ratio 1.10, 0.94 to 1.28) and those with estimated glomerular filtration rate below 60 mL/min (1.11, 0.88 to 1.41). CONCLUSIONS: Sitagliptin use was not associated with an excess risk of all cause hospital admission or death compared with other glucose lowering agents among newly treated patients with type 2 diabetes. Most patients prescribed sitagliptin in this cohort were concordant with clinical practice guidelines, in that it was used as add-on treatment.

Cost-effectiveness of a multifaceted intervention to improve quality of osteoporosis care after wrist fracture.

UNLABELLED: In a randomized trial, a multifaceted intervention tripled rates of osteoporosis treatment in older patients with wrist fracture. An economic analysis of the trial now demonstrates that the intervention tested "dominates" usual care: over a lifetime horizon, it reduces fracture, increases quality-adjusted life years, and saves the healthcare system money. INTRODUCTION: In a randomized trial (N = 272), we reported a multifaceted quality improvement intervention directed at older patients and their physicians could triple rates of osteoporosis treatment within 6 months of a wrist fracture when compared with usual care (22% vs 7%). Alongside the trial, we conducted an economic evaluation. METHODS: Using 1-year outcome data from our trial and micro-costing time-motion studies, we constructed a Markov decision-analytic model to determine cost-effectiveness of the intervention compared with usual care over the patients' remaining lifetime. We took the perspective of third-party healthcare payers. In the base case, costs and benefits were discounted at 3% and expressed in 2006 Canadian dollars. One-way deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Median age of patients was 60 years, 77% were women, and 72% had low bone mineral density (BMD). The intervention cost $12 per patient. Compared with usual care, the intervention strategy was dominant: for every 100 patients receiving the intervention, three fractures (one hip fracture) would be prevented, 1.1 quality-adjusted life year gained, and $26,800 saved by the healthcare system over their remaining lifetime. The intervention dominated usual care across numerous one-way sensitivity analyses: with respect to cost, the most influential parameter was drug price; in terms of effectiveness, the most influential parameter was rate of BMD testing. The intervention was cost saving in 80% of probabilistic model simulations. CONCLUSIONS: For outpatients with wrist fractures, our multifaceted osteoporosis intervention was cost-effective. Healthcare systems implementing similar interventions should expect to save money, reduce fractures, and gain quality-adjusted life expectancy.

Nurse case-manager vs multifaceted intervention to improve quality of osteoporosis care after wrist fracture: randomized controlled pilot study.

UNLABELLED: Few outpatients with fractures are treated for osteoporosis in the years following fracture. In a randomized pilot study, we found a nurse case-manager could double rates of osteoporosis testing and treatment compared with a proven efficacious quality improvement strategy directed at patients and physicians (57% vs 28% rates of appropriate care). INTRODUCTION: Few patients with fractures are treated for osteoporosis. An intervention directed at wrist fracture patients (education) and physicians (guidelines, reminders) tripled osteoporosis treatment rates compared to controls (22% vs 7% within 6 months of fracture). More effective strategies are needed. METHODS: We undertook a pilot study that compared a nurse case-manager to the multifaceted intervention using a randomized trial design. The case-manager counseled patients, arranged bone mineral density (BMD) tests, and prescribed treatments. We included controls from our first trial who remained untreated for osteoporosis 1-year post-fracture. Primary outcome was bisphosphonate treatment and secondary outcomes were BMD testing, appropriate care (BMD test-treatment if bone mass low), and costs. RESULTS: Forty six patients untreated 1-year after wrist fracture were randomized to case-manager (n = 21) or multifaceted intervention (n = 25). Median age was 60 years and 68% were female. Six months post-randomization, 9 (43%) case-managed patients were treated with bisphosphonates compared with 3 (12%) multifaceted intervention patients (relative risk [RR] 3.6, 95% confidence intervals [CI] 1.1-11.5, p = 0.019). Case-managed patients were more likely than multifaceted intervention patients to undergo BMD tests (81% vs 52%, RR 1.6, 95%CI 1.1-2.4, p = 0.042) and receive appropriate care (57% vs 28%, RR 2.0, 95%CI 1.0-4.2, p = 0.048). Case-management cost was $44 (CDN) per patient vs $12 for the multifaceted intervention. CONCLUSIONS: A nurse case-manager substantially increased rates of appropriate testing and treatment for osteoporosis in patients at high-risk of future fracture when compared with a multifaceted quality improvement intervention aimed at patients and physicians. Even with case-management, nearly half of patients did not receive appropriate care. TRIAL REGISTRY: clinicaltrials.gov identifier: NCT00152321.

Association between obesity and health-related quality of life in patients with coronary artery disease.

BACKGROUND AND OBJECTIVE: In patients with coronary artery disease (CAD), obesity is paradoxically associated with better survival (the 'obesity paradox'). Our objective was to determine whether this counterintuitive relationship extends to health-related quality of life (HRQOL) outcomes. DESIGN: Cross-sectional observational study. SUBJECTS: All adults undergoing coronary angiography residing in Alberta, Canada between January 2003 and March 2006 in the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) registry. METHODS: Patients completed self-reported questionnaires 1 year after their index cardiac catheterization, including the Seattle Angina Questionnaire (SAQ) and the EuroQol 5D (EQ-5D Index). Patients were grouped into six body mass index (BMI) categories (underweight, normal, overweight, mild obesity, moderate obesity and severe obesity). An analysis of covariance was used to create risk-adjusted scores. RESULTS: A total of 5362 patients were included in the analysis. Obese patients were younger than normal and overweight participants, and had a higher prevalence of depression and cardiovascular risk factors. In the adjusted models, SAQ physical function scores and the EQ Index (representing overall QOL) were significantly reduced in patients with mild, moderate and severe obesity compared with patients with a normal BMI. Patients with severe obesity had both statistically and clinically significant reductions in HRQOL scores. Depressive symptoms accounted for a large proportion in variability of all HRQOL scores. CONCLUSIONS: BMI is inversely associated with physical function and overall HRQOL in CAD patients, especially in patients with severe obesity. High body weight is a modifiable risk factor; however, given the apparent obesity paradox in patients with CAD, it is critical that future studies be conducted to fully clarify the relationships between HRQOL and body composition (body fat and lean mass), nutritional state and survival outcomes.

The effect of specialist care within the first year on subsequent outcomes in 24,232 adults with new-onset diabetes mellitus: population-based cohort study.

BACKGROUND: Although specialty care has been shown to improve short-term outcomes in patients hospitalised with acute medical conditions, its effect on patients with chronic conditions treated in the ambulatory care setting is less clear. OBJECTIVE: To examine whether specialty care (ie, consultative care provided by an endocrinologist or a general internist in concert with a patient's primary care doctor) within the first year of diagnosis is associated with improved outcomes after the first year for adults with diabetes mellitus treated as outpatients. DESIGN: Population-based cohort study using linked administrative data. SETTING: The province of Saskatchewan, Canada. SAMPLE: 24 232 adults newly diagnosed with diabetes mellitus between 1991 and 2001. METHOD: The primary outcome was all-cause mortality. Analyses used multivariate Cox proportional hazards models with time-dependent covariates, propensity scores and case mix variables (demographic, disease severity and comorbidities). In addition, restriction analyses examined the effect of specialist care in low-risk subgroups. RESULTS: The median age of patients was 61 years, and over a mean follow-up of 4.9 years 2932 (12%) died. Patients receiving specialty care were younger, had a greater burden of comorbidities, and visited doctors more often before and after their diabetes diagnosis (all p< or =0.001). Compared with patients seen by primary care doctors alone, patients seen by specialists and primary care doctors were more likely to receive recommended treatments (all p< or =0.001), but were more likely to die (13.1% v 11.7%, adjusted hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.08 to 1.27). This association persisted even in patients without comorbidities or target organ damage (adjusted HR 1.16, 95% CI 1.01 to 1.34). CONCLUSION: Specialty care was associated with better disease-specific process measures but not improved survival in adults with diabetes cared for in ambulatory care settings.

Use of beta-blockers for uncomplicated hypertension in the elderly: a cause for concern.

Beta-blockers are less beneficial than other antihypertensive drugs in the elderly with hypertension. All elderly patients in Ontario, Canada (population over 3.5 million elderly) without co-morbidities who were first treated for hypertension with a beta-blocker were studied in a retrospective population-based cohort study (1994-2002) to determine the characteristics of those prescribed beta-blockers. Of the 194,761 patients in our cohort, 25 485 (13%) were prescribed a beta-blocker as their first antihypertensive agent. On multivariate analysis, factors significantly associated with being prescribed a beta-blocker as first-line therapy included male sex (adjusted odds ratio (OR) 1.06 [95% CI 1.03-1.09] vs women), younger age (adjusted OR 1.67 [95% CI 1.55-1.79] for patients aged 66-69 vs those aged 85 or older), residence in a long-term care facility (adjusted OR 1.19 [95% CI 1.04-1.35] vs living in the community) and lower socioeconomic status (adjusted OR 1.07 [95% CI 1.02-1.12], for lowest quintile vs highest quintile). Patients with diabetes were substantially less likely to be prescribed beta-blockers (adjusted OR 0.42 [95% CI 0.40-0.44]). Greater efforts are required to educate physicians to select other drugs for initial therapy in older patients with uncomplicated hypertension.

The Canadian Hypertension Education Program--a unique Canadian initiative.

While almost two-thirds of all strokes and one-half of all myocardial infarctions could be prevented if hypertensive individuals had their blood pressures optimally controlled, only a minority of hypertensive individuals (even in publicly funded health care systems with subsidization of medication costs) achieve target blood pressures. Traditional hypertension guidelines have had limited impact on hypertension management and control rates. As a result, the Canadian Hypertension Education Program was developed to address the perceived flaws in the traditional hypertension guideline approach. In the present article, the key features of the Canadian Hypertension Education Program methodology are reviewed, with attention to those factors thought to be critical to the successful translation of recommendations into practice.