Background

Composite outcomes that weight each component equally are commonly used to study treatment effects. We hypothesized that each component of a composite outcome would differentially affect patients’ overall health-related quality of life (HRQL).

Methods

We tested our hypothesis using data from 2 published clinical studies of treatment for heart failure, one comparing metformin and sulfonylurea and the other comparing digoxin and placebo. We applied the quality-adjusted survival (QAS) approach, which incorporates HRQL data to accommodate differential weights for 2 components (in this analysis, death or admission to hospital) of a commonly used composite end point. For each of the 2 studies, the composite outcome was partitioned into its components, to which utility weights derived from the literature were assigned. Total QAS time determined for each treatment by the QAS analysis was compared with the results from traditional survival analyses based on Cox proportional hazards regression.

Results

In the observational study of metformin in heart failure, the risk of the composite outcome of death or admission to hospital was lower for those receiving metformin therapy than for those who received sulfonylurea (event rate 160 [77%] v. 658 [85%]; hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.70–0.99). With traditional survival analysis, the net gain was 0.82 years (95% CI 0.26–1.37), whereas the difference in QAS time was less, at 0.54 years (95% CI 0.20–0.89). In the randomized trial of digoxin therapy, the risk of the composite outcome was lower for those receiving the intervention than for those receiving placebo (event rate 1291 [38%] v. 1041 [31%]; HR 0.75, 95% CI 0.69–0.82). With traditional survival analysis, the net gain was 0.06 years (95% CI 0.02–0.16), whereas the difference in QAS time was greater, at 0.11 years (95% CI 0.06–0.16).

Interpretation

Studies that assume equal weights for the components of composite outcomes may overestimate or underestimate treatment effects. By incorporating HRQL into survival analyses, the impact of the various components of the outcome can be assessed more directly.

Introduction

Diabetes represents a major public health and health system burden. As part of the Alberta's Caring for Diabetes (ABCD) Project, two quality-improvement interventions are being piloted in four Primary Care Networks in Alberta. Gaps between health research, policy and practice have been documented and the need to evaluate the impact of public health interventions in real-world settings to inform decision-making and clinical practice is paramount. In this article, we describe the application of the RE-AIM framework to evaluate the interventions beyond effectiveness.

Methods and analysis

Two quality-improvement interventions were implemented, based on previously proven effective models of care and are directed at improving the physical and mental health of patients with type-2 diabetes. Our goal is to adapt and apply the RE-AIM framework, using a mixed-methods approach, to understand the impact of the interventions to inform policy and clinical decision-making. We present the proposed measures, data sources and data management and analysis strategies used to evaluate the interventions by RE-AIM dimension.

Ethics and dissemination

Ethics approval for the ABCD Project has been granted from the Health Research Ethics Board (HREB #PRO00012663) at the University of Alberta. The RE-AIM framework will be used to structure our dissemination activities by dimension.

Results

It will be presented at relevant conferences and prepared for publication in peer-reviewed journals. Various products, such as presentations, briefing reports and webinars, will be developed to inform key stakeholders of the findings. Presentation of findings by RE-AIM dimension will facilitate discussion regarding the public health impact of the two interventions within the primary care context of Alberta and lessons learned to be used in programme planning and care delivery for patients with type-2 diabetes. It will also promote the application of evaluation models to better assess the impact of community-based primary healthcare interventions through our dissemination activities.

Background

Bariatric surgery is the most effective current treatment for severe obesity. Capacity to perform surgery within Canada’s public health system is limited and potential candidates face protracted wait times. A better understanding of the gaps between demand for surgery and the capacity to provide it is required. The purpose of this study was to quantify and characterize the bariatric surgery-eligible population in Canada in comparison to surgery-ineligible subjects and surgical recipients.

Methods

Data from adult (age > 20) respondents of the 2007–09 nationally representative Canadian Health Measures Survey (CHMS) were analyzed to estimate the prevalence and characteristics of the surgery-eligible and ineligible populations. Federally mandated administrative healthcare data (2007–08) were used to characterize surgical recipients.

Results

In 2007–09, an estimated 1.5 million obese Canadian adults met eligibility criteria for bariatric surgery. 19.2 million were surgery-ineligible (3.4 million obese and 15.8 million non-obese). Surgery-eligible Canadians had a mean BMI of 40.1 kg/m2 (95% CI 39.3 to 40.9 kg/m2) and, compared to the surgery-ineligible obese population, were more likely to be female (62 vs. 44%), 40–59 years old (55 vs. 48%), less educated (43 vs. 35%), in the lowest socioeconomic tertile (41 vs. 34%), and inactive (73 vs. 59%). Self-rated mental health and quality of life were lower and comorbidity was higher in surgery-eligible respondents compared with the ineligible populations. The annual proportion of Canadians eligible for surgery that actually underwent a publicly funded bariatric surgery between 2007–09 was 0.1%. Surgical recipients (n = 847) had a mean age of 43.6 years (SD 11.1) and 82% were female. With the exception of type 2 diabetes, obesity-related comorbidity prevalence was much lower in surgical recipients compared to those eligible for surgery.

Conclusions

The proportion of bariatric surgery-eligible Canadians that undergo publicly funded bariatric surgery is very low. There are notable differences in sociodemographic profiles and prevalence of comorbidities between surgery-eligible subjects and surgical recipients.

Background:

Patients with type 2 diabetes have a 40% increased risk of bladder cancer. Thiazolidinediones, especially pioglitazone, may increase the risk. We conducted a systematic review and meta-analysis to evaluate the risk of bladder cancer among adults with type 2 diabetes taking thiazolidinediones.

Methods:

We searched key biomedical databases (including MEDLINE, Embase and Scopus) and sources of grey literature from inception through March 2012 for published and unpublished studies, without language restrictions. We included randomized controlled trials (RCTs), cohort studies and case–control studies that reported incident bladder cancer among people with type 2 diabetes who ever (v. never) were exposed to pioglitazone (main outcome), rosiglitazone or any thiazolidinedione.

Results:

Of the 1787 studies identified, we selected 4 RCTs, 5 cohort studies and 1 case–control study. The total number of patients was 2 657 365, of whom 3643 had newly diagnosed bladder cancer, for an overall incidence of 53.1 per 100 000 person-years. The one RCT that reported on pioglitazone use found no significant association with bladder cancer (risk ratio [RR] 2.36, 95% confidence interval [CI] 0.91–6.13). The cohort studies of thiazolidinediones (pooled RR 1.15, 95% CI 1.04–1.26; I2 = 0%) and of pioglitazone specifically (pooled RR 1.22, 95% CI 1.07–1.39; I2 = 0%) showed significant associations with bladder cancer. No significant association with bladder cancer was observed in the two RCTs that evaluated rosiglitazone use (pooled RR 0.87, 95% CI 0.34–2.23; I2 = 0%).

Interpretation:

The limited evidence available supports the hypothesis that thiazolidinediones, particularly pioglitazone, are associated with an increased risk of bladder cancer among adults with type 2 diabetes.

Background

The vast majority of research in the area of community-acquired pneumonia (CAP) has been based on patients admitted to hospital. And yet, the majority of patients with CAP are treated on an ambulatory basis as outpatients, either by primary care physicians or in Emergency Departments. Few studies have been conducted in outpatients with pneumonia, and there is a paucity of data on short and long term morbidity or mortality and associated clinical correlates in this group of patients.

Methods

From 2000–2002, all CAP patients presenting to 7 Emergency Departments in Edmonton, Alberta, Canada were prospectively enrolled in a population-based registry. Clinical data, including pneumonia severity index (PSI) were collected at time of presentation. Patients discharged to the community were then followed for up to 5 years through linkage to the provincial administrative databases. The current report provides the rationale and design for the cohort, as well as describes baseline characteristics and 30-day morbidity and mortality.

Results

The total sample included 3874 patients. After excluding patients who were hospitalized, died or returned to the Emergency Department the same day they were initially discharged (n = 451; 12 %), and patients who could not be linked to provincial administrative databases (n = 237; 6 %), the final cohort included 3186 patients treated according to a validated clinical management pathway and discharged back to the community. Mean age was 51 (SD = 20) years, 53 % male; 4 % resided in a nursing home, 95 % were independently mobile, and 88 % had mild (PSI class I-III) pneumonia. Within 30-days, return to Emergency Department was common (25 %) as was hospitalization (8 %) and 1 % of patients had died.

Conclusions

To our knowledge, this represents the largest clinically-detailed outpatient CAP cohort assembled to date and will add to our understanding of the determinants and outcomes in this under-researched patient population. The rich clinical data along with the long term health care utilization and mortality will allow for the identification of novel prognostic indicators. Given how under studied this population is, the findings should aid clinicians in the routine care of their outpatients with pneumonia and help define the next generation of research questions.

Background

Protracted, multi-year wait times exist for bariatric care in Canada. Our objective was to examine wait-listed patients’ health status and perceptions regarding the consequences of prolonged wait times using a cross-sectional study design nested within a prospective cohort.

Methods

150 consecutive consenting subjects wait-listed for multi-disciplinary bariatric assessment in a population-based medical/surgical bariatric program were surveyed. Health status was measured using a visual analogue scale (VAS). A Waiting List Impact Questionnaire (WLIQ) examined employment, physical stress, social support, frustration, quality of life, and satisfaction with care. Multivariable linear regression analysis adjusted for age, sex and BMI identified independent predictors of lower VAS scores.

Results

136 (91%) subjects were women, mean age was 43 years (SD 9), mean BMI was 49.4 (SD 8.3) kg/m2 and average time wait-listed was 64 days (SD 76). The mean VAS score was 53/100 (SD 22). According to the WLIQ, 47% of subjects agreed/strongly agreed that waiting affected their quality of life, 65% described wait times as ‘concerning’ and 81% as ‘frustrating’. 86% reported worsening of physical symptoms over time. Nevertheless, only 31% were dissatisfied/very dissatisfied with their overall medical care. Independent predictors of lower VAS scores were higher BMI (beta coefficient 0.42; p = 0.03), unemployment (13.7; p = 0.01) and depression (10.3; p = 0.003).

Conclusions

Patients wait-listed for bariatric care self-reported very impaired health status and other adverse consequences, attributing these to protracted waits. These data may help benchmark the level of health impairment in this population, understand the physical and mental toll of waiting, and assist with wait list management.

Trial registration

Clinicaltrials.gov NCT00850356

Background

Elderly individuals who have memory problems without significant limitations in activities of daily living are often diagnosed as having mild cognitive impairment (MCI). Some of these individuals progress to dementia. Several cognitive enhancers (for example donepezil, galantamine, rivastigmine, memantine) have been approved for use in people with Alzheimer’s dementia but their use in patients with MCI is unclear. We aimed to determine the comparative effectiveness, safety, and cost of cognitive enhancers for MCI through a systematic review and network (that is, indirect comparisons) meta-analysis.

Design/Methods

We will include studies that examine the use of cognitive enhancers compared to placebo, supportive care, or other cognitive enhancers among patients diagnosed with MCI. Outcomes of interest include cognition and function (primary outcomes), as well as behavior, quality of life, safety, and cost (secondary outcomes). We will include all experimental studies (randomized controlled trials, quasi-randomized controlled trials, controlled clinical trials), quasi-experimental studies (controlled before-after, interrupted time series), and observational studies (cohort, case–control). Studies will be included regardless of publication status (that is, we will include unpublished studies), year, or language of dissemination.

To identify potentially relevant material, we will search the following electronic databases from inception onwards: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, and Ageline. The electronic database search will be supplemented by scanning the reference lists of included studies, searching Google and organization websites for unpublished or difficult to locate material literature, and contacting experts.

Two reviewers will independently screen the studies for inclusion using the eligibility criteria established a priori and independently extract data. Risk of bias will be assessed using the Cochrane Risk of Bias tool for experimental and quasi-experimental studies and the Newcastle Ottawa Scale for observational epidemiology studies. Meta-analysis and network meta-analysis are planned, if the studies are deemed statistically, methodologically, and clinically homogenous.

Discussion

Our systematic review will provide important information regarding the benefits, costs, and harms of cognitive enhancers for patients with MCI. This information can be used to assist healthcare providers, policy-makers, MCI patients and their family regarding the use of these agents.

PROSPERO registry number

CRD42012002234

Objective

To improve the understanding of the determinants of prognosis and accurate risk stratification in community-acquired pneumonia (CAP).

Design

Multicentre collaboration of prospective cohorts.

Setting

6 cohorts from the USA, Canada, Hong Kong and Spain.

Participants

From a published meta-analysis of risk stratification studies in CAP, the authors identified and pooled individual patient-level data from six prospective cohort studies of CAP (three from the USA, one each from Canada, Hong Kong and Spain) to create the International CAP Collaboration Cohort. Initial essential inclusion criteria of meta-analysis were (1) prospective design, (2) in English language, (3) reported 30-day mortality and transfer to an intensive or high dependency care and (4) minimum 1000 participants. Common baseline patient characteristics included demographics, history and physical examination findings, comorbidities and laboratory and radiographic findings.

Primary and secondary outcome measures

This paper reports the rationale, hypotheses and analytical framework and also describes study cohorts and patients. The authors aim to (1) compare the prognostic accuracy of existing CAP risk stratification tools, (2) assess patient-level determinants of prognosis, (3) improve risk stratification by combined use of scoring systems and (4) understand prognostic factors for specific patient groups.

Results

The six cohorts assembled from 1991 to 2007 included 13 784 patients (median age 71 years, 54% men). Aside from one randomised controlled study, the remaining five were cohort studies, but all had similar inclusion criteria. Overall, there was 0%–6% missing data. A total of 6159 (44%) had severe pneumonia by Pneumonia Severity Index class IV/V. Mortality at 30 days was 8% (1036). Admission to intensive care or high dependency unit was also 8% (1059).

Conclusions

International CAP Collaboration Cohort provides a pooled multicentre data set of patients with CAP, which will help us to better understand the prognosis of CAP.

Article summary

Article focus

This paper reports the rationale, hypotheses and analytical framework and also describes study cohorts and patients. We aim to

compare the prognostic accuracy of existing CAP risk stratification tools;

assess patient-level determinants of prognosis;

improve risk stratification by combined use of scoring systems;

understand prognostic factors for specific patient groups.

Key messages

The International CAP Collaboration Cohort (ICCC) as described in this report will be able to provide better understanding of determinants of outcomes in CAP. Examples of such development include comparison of commonly and less commonly known CAP severity scoring systems and identification of characteristics of CAP patients with poor outcome (30-day mortality) despite non-severe status of severity score.

In view of the large sample size, the ICCC cohort will be able to provide the determinants of outcomes in patient groups with specific conditions such as cardiovascular and respiratory diseases taking into account case mix and individual prognostic indicators.

The ICCC cohort will be of benefit to the CAP research community and help define a future agenda for research, as well as helping clinicians make better clinical decisions for patients with CAP.

Strengths and limitations of this study

The ICCC is a multicentre/multiethnic cohort where all collaborating groups defined pneumonia based on clinical features and the presence of CXR evidence of pneumonia. The major strengths of ICCC are prospective study design, inclusion of CAP patients spanning across wide age range, ethnicity, different healthcare settings and large sample size. Potential areas of improvement in assessment of CAP might be identification of at-risk patients with pneumonia who have been initially assessed as non-severe CAP. With large sample size, ICCC may provide an opportunity to identify characteristics of such individuals. Based on this work, risk assessment may be applied at more than one point in time in order to observe temporal trends in recovery or deterioration in future CAP research and clinical practice.

There were multiple observers and data collections across several centres. However, all cohorts followed the strict criteria in data collection as described in table 1. Furthermore, the data collected were objective measures such as age and urea level, thereby ruling out potential observer bias. The process of care between hospitals may be variable. There may be a variation in clinical management between different hospitals and in different healthcare setting between the various countries such as there may be important variations in antibiotic use, patterns of infective micro-organisms, care protocols and treatment guidelines. Other limitations to consider are biomarkers, healthcare provider and site characteristics. The patients were enrolled into the study at different time periods. However, this presents an opportunity to compare and contrast different healthcare systems to better understand the variation in healthcare setting and outcomes. Since all six studies used the Pneumonia Severity Index (PSI) for risk stratification, this can have implications, for example, patients who scored non-severe at initial assessment (low PSI) but might have had worse outcome are under-represented if such patients were sent home. This could contribute to attenuation of estimates in low PSI group. Nevertheless, it is possible that these patients would have presented again to the medical centre if/when deterioration occurred. Cohorts that only had data on CURB-related variables and cohorts with smaller sample sizes were not included in the ICCC, and this may introduce some degree of selection bias. Nevertheless, this should not have any effect on the internal relationship between the predictors and outcomes of interest.

OBJECTIVE

To evaluate the effect of adding pharmacists to primary care teams on the management of hypertension and other cardiovascular risk factors in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

We conducted a randomized controlled trial with blinded ascertainment of outcomes within primary care clinics in Edmonton, Canada. Pharmacists performed medication assessments and limited history and physical examinations and provided guideline-concordant recommendations to optimize medication management. Follow-up contact was completed as necessary. Control patients received usual care. The primary outcome was a ≥10% decrease in systolic blood pressure at 1 year.

RESULTS

A total of 260 patients were enrolled, 57% were women, the mean age was 59 years, diabetes duration was 6 years, and blood pressure was 129/74 mmHg. Forty-eight of 131 (37%) intervention patients and 30 of 129 (23%) control patients achieved the primary outcome (odds ratio 1.9 [95% CI 1.1–3.3]; P = 0.02). Among 153 patients with inadequately controlled hypertension at baseline, intervention patients (n = 82) were significantly more likely than control patients (n = 71) to achieve the primary outcome (41 [50%] vs. 20 [28%]; 2.6 [1.3–5.0]; P = 0.007) and recommended blood pressure targets (44 [54%] vs. 21 [30%]; 2.8 [1.4–5.4]; P = 0.003). The 10-year risk of cardiovascular disease, based on changes to the UK Prospective Diabetes Study Risk Engine, were predicted to decrease by 3% for intervention patients and 1% for control patients (P = 0.005).

CONCLUSIONS

Significantly more patients with type 2 diabetes achieved better blood pressure control when pharmacists were added to primary care teams, which suggests that pharmacists can make important contributions to the primary care of these patients.

Background

Globally, healthcare systems are attempting to optimize quality of care. This challenge has resulted in the development of implementation science or knowledge translation (KT) and the resulting need to build capacity in both the science and practice of KT.

Findings

We are attempting to meet these challenges through the creation of a national training initiative in KT. We have identified core competencies in this field and have developed a series of educational courses and materials for three training streams. We report the outline for this approach and the progress to date.

Conclusions

We have prepared a strategy to develop, implement, and evaluate a national training initiative to build capacity in the science and practice of KT. Ultimately through this initiative, we hope to meet the capacity demand for KT researchers and practitioners in Canada that will lead to improved care and a strengthened healthcare system.

OBJECTIVE

Diabetes and heart failure commonly coexist, and prior studies have suggested better outcomes with metformin than other antidiabetic agents. We designed this study to determine whether this association reflects a beneficial effect of metformin or a harmful effect of other agents.

RESEARCH DESIGN AND METHODS

We performed a case-control study nested within the U.K. General Practice Research Database cohort in which diagnoses were assigned by each patient's primary care physician. Case subjects were patients 35 years or older, newly diagnosed with both heart failure and diabetes after January 1988, and who died prior to October 2007. Control subjects were matched to case subjects based on age, sex, clinic site, calendar year, and duration of follow-up. Analyses were adjusted for comorbidities, A1C, renal function, and BMI.

RESULTS

The duration of concurrent diabetes and heart failure was 2.8 years (SD 2.6) in our 1,633 case subjects and 1,633 control subjects (mean age 78 years, 53% male). Compared with patients who were not exposed to antidiabetic drugs, the current use of metformin monotherapy (adjusted odds ratio 0.65 [0.48–0.87]) or metformin with or without other agents (0.72 [0.59–0.90]) was associated with lower mortality; however, use of other antidiabetic drugs or insulin was not associated with all-cause mortality. Conversely, the use of ACE inhibitors/angiotensin receptor blockers (0.55 [0.45–0.68]) and β-blockers (0.76 [0.61–0.95]) were associated with reduced mortality.

CONCLUSIONS

Our results confirm the benefits of trial-proven anti-failure therapies in patients with diabetes and support the use of metformin-based strategies to lower glucose.

BACKGROUND:

Glucose-insulin infusions (with potassium [GIK] or without [GI]) have been advocated in the setting of coronary artery bypass graft (CABG) surgery to optimize myocardial glucose use and to minimize ischemic injury.

OBJECTIVE:

To conduct a meta-analysis assessing whether the use of GIK/GI infusions perioperatively reduce in-hospital mortality or atrial fibrillation (AF) after CABG surgery.

METHODS:

Electronic databases (Medline, EMBASE and Cochrane Central Register of Controlled Trials [CENTRAL]) and references of retrieved articles were searched for randomized controlled trials that evaluated the effects of GIK or GI infusions, before or during CABG surgery, on in-hospital mortality and/or postoperative AF. Pooled ORs and 95% CIs were calculated for each outcome.

RESULTS:

Twenty trials were identified and eligible for review. The summary OR for in-hospital mortality was 0.88 (95% CI 0.56 to 1.40), based on 44 deaths among 2326 patients. While postoperative AF was a more frequent outcome (occurring in 519 of 1540 patients in the 10 trials reporting this outcome), the overall pooled estimate of effect was nonsignificant (OR 0.79, 95% CI 0.54 to 1.15). This latter finding needs to be interpreted cautiously because it is accompanied by significant heterogeneity across trials.

CONCLUSIONS:

Perioperative use of GIK/GI does not significantly reduce mortality or atrial fibrillation in patients undergoing CABG surgery. Unless future trial data in support of GIK/GI infusions become available, the routine use of these treatments in patients undergoing CABG surgery should be discouraged because the safety of these infusions has not been systematically examined.

The risk is negligible, and does not offset the benefits of reducing fractures

Objective To assess the impact of a pay for performance incentive on quality of care and outcomes among UK patients with hypertension in primary care.

Design Interrupted time series.

Setting The Health Improvement Network (THIN) database, United Kingdom.

Participants 470 725 patients with hypertension diagnosed between January 2000 and August 2007.

Intervention The UK pay for performance incentive (the Quality and Outcomes Framework), which was implemented in April 2004 and included specific targets for general practitioners to show high quality care for patients with hypertension (and other diseases).

Main outcome measures Centiles of systolic and diastolic blood pressures over time, rates of blood pressure monitoring, blood pressure control, and treatment intensity at monthly intervals for baseline (48 months) and 36 months after the implementation of pay for performance. Cumulative incidence of major hypertension related outcomes and all cause mortality for subgroups of newly treated (treatment started six months before pay for performance) and treatment experienced (started treatment in year before January 2001) patients to examine different stages of illness.

Results After accounting for secular trends, no changes in blood pressure monitoring (level change 0.85, 95% confidence interval −3.04 to 4.74, P=0.669 and trend change −0.01, −0.24 to 0.21, P=0.615), control (−1.19, −2.06 to 1.09, P=0.109 and −0.01, −0.06 to 0.03, P=0.569), or treatment intensity (0.67, −1.27 to 2.81, P=0.412 and 0.02, −0.23 to 0.19, P=0.706) were attributable to pay for performance. Pay for performance had no effect on the cumulative incidence of stroke, myocardial infarction, renal failure, heart failure, or all cause mortality in both treatment experienced and newly treated subgroups.

Conclusions Good quality of care for hypertension was stable or improving before pay for performance was introduced. Pay for performance had no discernible effects on processes of care or on hypertension related clinical outcomes. Generous financial incentives, as designed in the UK pay for performance policy, may not be sufficient to improve quality of care and outcomes for hypertension and other common chronic conditions.

Background

Granting dispensing pharmacists the authority to prescribe has significant implications for pharmaceutical and health human resources policy, and quality of care. Despite the growing number of jurisdictions that have given pharmacists such privileges, there are few rigorous evaluations of these policy changes. This study will examine a January 2009 policy change in British Columbia (BC), Canada that allowed pharmacists to independently adapt and renew prescriptions. We hypothesize this policy increased drug utilization and drug costs, increased patient adherence to medication, and reduced total healthcare resource use.

Methods/Design

We will study a population-based cohort of approximately 4 million BC residents from 2004 through 2010. We will use data from BC PharmaNet on all of the prescriptions obtained by this cohort during the study period, and link it to administrative billings from physicians and hospital discharges. Using interrupted time series analysis, we will study longitudinal changes in drug utilization and costs, medication adherence, and short-term health care use. Further, using hierarchical modelling, we will examine the factors at the regional, pharmacy, patient, and prescription levels that are associated with prescription adaptations and renewals.

Discussion

In a recent survey of Canadian policymakers, many respondents ranked the issue of prescribing privileges as one of their most pressing policy questions. No matter the results of our study, they will be important for policymakers, as our data will make policy decisions surrounding pharmacist prescribing more evidence-based.

Background

Extreme obesity affects nearly 8% of Canadians, and is debilitating, costly and ultimately lethal. Bariatric surgery is currently the most effective treatment available; is associated with reductions in morbidity/mortality, improvements in quality of life; and appears cost-effective. However, current demand for surgery in Canada outstrips capacity by at least 1000-fold, causing exponential increases in already protracted, multi-year wait-times. The objectives and hypotheses of this study were as follows: 1. To serially assess the clinical, economic and humanistic outcomes in patients wait-listed for bariatric care over a 2-year period. We hypothesize deterioration in these outcomes over time; 2. To determine the clinical effectiveness and changes in quality of life associated with modern bariatric procedures compared with medically treated and wait-listed controls over 2 years. We hypothesize that surgery will markedly reduce weight, decrease the need for unplanned medical care, and increase quality of life; 3. To conduct a 3-year (1 year retrospective and 2 year prospective) economic assessment of bariatric surgery compared to medical and wait-listed controls from the societal, public payor, and health-care payor perspectives. We hypothesize that lower indirect, out of pocket and productivity costs will offset increased direct health-care costs resulting in lower total costs for bariatric surgery.

Methods/design

Population-based prospective cohort study of 500 consecutive, consenting adults, including 150 surgically treated patients, 200 medically treated patients and 150 wait-listed patients. Subjects will be enrolled from the Edmonton Weight Wise Regional Obesity Program (Edmonton, Alberta, Canada), with prospective bi-annual follow-up for 2 years. Mixed methods data collection, linking primary data to provincial administrative databases will be employed. Major outcomes include generic, obesity-specific and preference-based quality of life assessment, patient satisfaction, patient utilities, anthropometric indices, cardiovascular risk factors, health care utilization and direct and indirect costs.

Discussion

The results will identify the spectrum of potential risks associated with protracted wait times for bariatric care and will quantify the economic, humanistic and clinical impact of surgery from the Canadian perspective. Such information is urgently needed by health-service providers and policy makers to better allocate use of finite resources. Furthermore, our findings should be widely-applicable to other publically-funded jurisdictions providing similar care to the extremely obese.

Trial Registration

Clinicaltrials.gov NCT00850356

Background

Survivors of transient ischemic attack (TIA) or stroke are at high risk for recurrent vascular events and aggressive treatment of vascular risk factors can reduce this risk. However, vascular risk factors, especially hypertension and high cholesterol, are not managed optimally even in those patients seen in specialized clinics. This gap between the evidence for secondary prevention of stroke and the clinical reality leads to suboptimal patient outcomes. In this study, we will be testing a pharmacist case manager for delivery of stroke prevention services. We hypothesize this new structure will improve processes of care which in turn should lead to improved outcomes.

Methods

We will conduct a prospective, randomized, controlled open-label with blinded ascertainment of outcomes (PROBE) trial. Treatment allocation will be concealed from the study personnel, and all outcomes will be collected in an independent and blinded manner by observers who have not been involved in the patient's clinical care or trial participation and who are masked to baseline measurements. Patients will be randomized to control or a pharmacist case manager treating vascular risk factors to guideline-recommended target levels. Eligible patients will include all adult patients seen at stroke prevention clinics in Edmonton, Alberta after an ischemic stroke or TIA who have uncontrolled hypertension (defined as systolic blood pressure (BP) > 140 mm Hg) or dyslipidemia (fasting LDL-cholesterol > 2.00 mmol/L) and who are not cognitively impaired or institutionalized. The primary outcome will be the proportion of subjects who attain 'optimal BP and lipid control'(defined as systolic BP < 140 mm Hg and fasting LDL cholesterol < 2.0 mmol/L) at six months compared to baseline; 12-month data will also be collected for analyses of sustainability of any effects. A variety of secondary outcomes related to vascular risk and health-related quality of life will also be collected.

Conclusions

Nearly one-quarter of those who survive a TIA or minor stroke suffer another vascular event within a year. If our intervention improves the provision of secondary prevention therapies in these patients, the clinical (and financial) implications will be enormous.

OBJECTIVE

Admission hyperglycemia has been associated with worse outcomes in ischemic stroke. We hypothesized that hyperglycemia (glucose >8.0 mmol/l) in the hyperacute phase would be independently associated with increased mortality, symptomatic intracerebral hemorrhage (SICH), and poor functional status at 90 days in stroke patients treated with intravenous tissue plasminogen activator (IV-tPA).

RESEARCH DESIGN AND METHODS

Using data from the prospective, multicenter Canadian Alteplase for Stroke Effectiveness Study (CASES), the association between admission glucose >8.0 mmol/l and mortality, SICH, and poor functional status at 90 days (modified Rankin Scale >1) was examined. Similar analyses examining glucose as a continuous measure were conducted.

RESULTS

Of 1,098 patients, 296 (27%) had admission hyperglycemia, including 18% of those without diabetes and 70% of those with diabetes. After multivariable logistic regression, admission hyperglycemia was found to be independently associated with increased risk of death (adjusted risk ratio 1.5 [95% CI 1.2–1.9]), SICH (1.69 [0.95–3.00]), and a decreased probability of a favorable outcome at 90 days (0.7 [0.5–0.9]). An incremental risk of death and SICH and unfavorable 90-day outcomes was observed with increasing admission glucose. This observation held true for patients with and without diabetes.

CONCLUSIONS

In this cohort of IV-tPA–treated stroke patients, admission hyperglycemia was independently associated with increased risk of death, SICH, and poor functional status at 90 days. Treatment trials continue to be urgently needed to determine whether this is a modifiable risk factor for poor outcome.

Background

Proven efficacious therapies are sometimes underused in patients with chronic cardiac conditions, resulting in suboptimal outcomes. We evaluated whether evidence summaries, which were either unsigned or signed by local opinion leaders, improved the quality of secondary prevention care delivered by primary care physicians of patients with coronary artery disease.

Methods

We performed a randomized trial, clustered at the level of the primary care physician, with 3 study arms: control, unsigned statements or opinion leader statements. The statements were faxed to primary care physicians of adults with coronary artery disease at the time of elective cardiac catheterization. The primary outcome was improvement in statin management (initiation or dose increase) 6 months after catheterization.

Results

We enrolled 480 adults from 252 practices. Although statin use was high at baseline (n = 316 [66%]), most patients were taking a low dose (mean 32% of the guideline-recommended dose), and their low-density lipoprotein (LDL) cholesterol levels were elevated (mean 3.09 mmol/L). Six months after catheterization, statin management had improved in 79 of 157 patients (50%) in the control arm, 85 of 158 (54%) patients in the unsigned statement group (adjusted odds ratio [OR] 1.18, 95% CI 0.71–1.94, p = 0.52) and 99 of 165 (60%) patients in the opinion leader statement group (adjusted OR 1.51, 95% CI 0.94–2.42, p = 0.09). The mean fasting LDL cholesterol levels after 6 months were similar in all 3 study arms: 2.35 (standard deviation [SD] 0.86) mmol/L in the control arm compared with 2.24 (SD 0.73) among those in the opinion leader group (p = 0.48) and 2.19 (SD 0.68) in the unsigned statement group (p = 0.32).

Interpretation

Faxed evidence reminders for primary care physicians, even when endorsed by local opinion leaders, were insufficient to optimize the quality of care for adults with coronary artery disease. ClinicalTrials.gov trial register no. NCT00175240.

Objective

Metformin has had a 'black box' contraindication in diabetic patients with heart failure (HF), but many believe it to be the treatment of choice in this setting. Therefore, we attempted to conduct a pilot study to evaluate the feasibility of undertaking a large randomized controlled trial with clinical endpoints.

Study Design

The pilot study was a randomized double blinded placebo controlled trial. Patients with HF and type 2 diabetes were screened in hospitals and HF clinics in Edmonton, Alberta, Canada (population ~1 million). Major exclusion criteria included the current use of insulin or high dose metformin, decreased renal function, or a glycosylated hemoglobin <7%. Patients were to be randomized to 1500 mg of metformin daily or matching placebo and followed for 6 months for a variety of functional outcomes, as well as clinical events.

Results

Fifty-eight patients were screened over a six month period and all were excluded. Because of futility with respect to enrollment, the pilot study was abandoned. The mean age of screened patients was 77 (SD 9) years and 57% were male. The main reasons for exclusion were: use of insulin therapy (n = 23; 40%), glycosylated hemoglobin <7% (n = 17; 29%) and current use of high dose metformin (n = 12; 21%). Overall, contraindicated metformin therapy was the most commonly prescribed oral antihyperglycemic agent (n = 27; 51%). On average, patients were receiving 1,706 mg (SD 488 mg) of metformin daily and 12 (44%) used only metformin.

Conclusion

Despite uncertainty in the scientific literature, there does not appear to be clinical uncertainty with regards to the safety or effectiveness of metformin in HF making a definitive randomized trial virtually impossible.

Trial registration

ClinicalTrials.gov Identifier: NCT00325910