The 2003 Canadian recommendations for dyslipidemia management: revisions are needed.
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Adolescent↗
Biomedical subjects
Andreas Laupacis
Publications and source records attributed to Andreas Laupacis.
The Canadian Stroke Quality of Care Study: establishing indicators for optimal acute stroke care.
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Benchmarking↗
Risk of upper gastrointestinal hemorrhage in warfarin users treated with nonselective NSAIDs or COX-2 inhibitors.
BACKGROUND: Little is known about the risk of upper gastrointestinal (GI) hemorrhage during the concomitant use of warfarin and selective cyclooxygenase (COX)-2 inhibitors. We examined the association between the concomitant use of warfarin and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) or selective COX-2 inhibitors in older adults hospitalized for upper GI hemorrhage. METHODS: This nested case-control analysis of multiple linked health care databases conducted over 1 year identified a cohort of patients in Ontario, Canada, who were older than 66 years and continuously prescribed warfarin. Case patients were those admitted to the hospital with upper GI hemorrhage while taking warfarin. We compared their prescription records prior to hospitalization with those of age- and sex-matched controls who were also receiving warfarin (the control-case ratio was 4:1). Odds ratios (ORs) for the risk of hospitalization for upper GI hemorrhage while concomitantly using warfarin and celecoxib, rofecoxib, or nonselective NSAIDs were determined. RESULTS: During the study period, we identified 98 821 elderly patients continuously receiving warfarin. Of those, 361 (0.3%) were admitted to the hospital with upper GI hemorrhage. After adjusting for other potential confounders, case patients were significantly more likely to be also taking nonselective NSAIDs (OR, 1.9; 95% confidence interval [CI], 1.4-3.7), celecoxib (OR, 1.7; 95% CI, 1.2-3.6), or rofecoxib (OR, 2.4; 95% CI, 1.7-3.6) prior to hospitalization relative to controls. CONCLUSIONS: Patients taking warfarin concomitantly with selective COX-2 inhibitors have an increased risk of hospitalization for upper GI hemorrhage. The risk appears similar to that of patients simultaneously taking warfarin and nonselective NSAIDs.
Age Distribution↗
A systematic review of the Charlson comorbidity index using Canadian administrative databases: a perspective on risk adjustment in critical care research.
The Charlson index is commonly used for risk adjustment in critical care health services research. However, the literature supporting this methodology has not been thoroughly explored. We systematically reviewed the literature related to administrative database adaptations of the Charlson index. Our review has 3 major findings. First, 2 studies compared Canadian administrative databases with chart review for obtaining Charlson comorbidity data. Agreement between the database and chart review was substantial (kappa > 0.70), and mortality prediction did not differ. Second, 5 database adaptations were identified with the Deyo and Dartmouth-Manitoba adaptations being most popular. Three studies directly compared these 2 popular adaptations and demonstrated substantial agreement (kappa > 0.70) and similar predictive ability for mortality. Third, one study validated the Charlson index for critically ill patients but demonstrated that APACHE (Acute Physiology and Chronic Health Evaluation) II better discriminates inhospital mortality (area under curve 0.67 vs 0.87). Time and cost barriers prevent widespread use of physiology-based risk adjustment in population-based research. The decreased predictive ability of the Charlson index must be weighed against the advantages of using this instrument for population-based research. Future research should focus on updating the Charlson index for recent changes in the prognosis of comorbid diseases and introduction of International Statistical Classification of Diseases, 10th Revision coding of discharge abstracts.
Canada↗
Projected incidence of mechanical ventilation in Ontario to 2026: Preparing for the aging baby boomers.
OBJECTIVE: The aging baby boomers are expected to have a significant impact on the healthcare system. Mechanical ventilation is an age-dependent, costly, and relatively nondiscretionary medical service that may be particularly affected by the aging population. We forecast the future incidence of mechanical ventilation to the year 2026 to understand the impact of aging baby boomers on critical care resources. DESIGN: Population-based, sex-specific, and age-specific mechanical ventilation incidences for adults for the year 2000 were directly standardized to population projections to estimate the incidence of mechanical ventilation, in 5-yr intervals, from 2006 to 2026. Sensitivity analyses were performed by varying population projections and mechanical ventilation incidence for the elderly. SETTING: Province of Ontario, Canada. PATIENTS: Noncardiac surgery, mechanically ventilated adults. INTERVENTIONS: None. MAIN RESULTS: The projected number of ventilated patients in 2026 was 34,478, representing an 80% increase from 2000. The crude incidence increased 31%, from 222 to 291 per 100,000 adults. The annually compounded projected growth rate during this 26-yr period was 2.3%, similar to the actual growth rate experienced in the 1990s. The projected incidence was relatively insensitive to changes in assumptions, with estimates for 2026 ranging from 31,473 to 36,313 ventilated adults. CONCLUSIONS: The incidence of mechanical ventilation projected to the year 2026 will steadily increase and outpace population growth as occurred in the 1990s. In the current environment in which intensive care unit resources are limited and ventilated patients already use a significant proportion of acute care resources, planning for this continued growth is necessary. Existing evidence-based strategies that improve both the efficiency and efficacy of critical care services should be carefully evaluated for widespread implementation.
Adult↗
Incorporating economic evaluations into decision-making: the Ontario experience.
The Drug Quality and Therapeutics Committee (DQTC) and the Canadian Expert Drug Assessment Committee (CEDAC) make reimbursement recommendations to publicly funded outpatient drug plans in Ontario and Canada respectively. In this article, the organization and decision-making processes of these committees are described. Issues associated with these committees such as potential biases associated with pharmaceutical company submissions, transparency, restricted access programs, conditional listing, and price negotiation are discussed.
Cost-Benefit Analysis↗
A population-based assessment of the potential interaction between serotonin-specific reuptake inhibitors and digoxin.
AIM: In vitro evidence suggests that some serotonin-specific reuptake inhibitors (SSRIs) inhibit P-glycoprotein, a multidrug efflux pump responsible for the elimination of several drugs including digoxin. We sought to determine if some SSRIs cause digoxin toxicity in the clinical setting. METHODS: Population-based nested case-control study set in Ontario, Canada from 1994 to 2001. We studied all patients 66 years or older treated with digoxin. Prescription and hospital admission records were analysed to determine the relationship between the initiation of SSRI therapy and hospital admission for digoxin toxicity in the subsequent 30 days. RESULTS: Among 245 305 older patients treated with digoxin, we identified 3144 cases of digoxin toxicity. After adjusting for potential confounders, we observed an increased risk of digoxin toxicity following initiation of paroxetine [odds ratio (OR) 2.8; 95% confidence interval (CI) 1.6, 4.7], fluoxetine (OR 2.9; 95% CI 1.5, 5.4), sertraline (OR 3.0; 95% CI 1.9, 4.7), and fluvoxamine (OR 3.0; 95% CI 1.5, 5.7). However, an elevated risk was also seen with tricyclic antidepressants (OR 1.5; 95% CI 1.0, 2.4) and benzodiazepines (OR 2.1; 95% CI 1.7, 2.5), drugs classes having no known pharmacokinetic interaction with digoxin. There was no statistical difference in the risk of digoxin toxicity among any of the agents tested. CONCLUSIONS: We found no major discrepancy in the risk of digoxin toxicity after initiation of various SSRI antidepressants, suggesting that the inhibition of P-glycoprotein by sertraline and paroxetine observed in vitro is unlikely to be of major clinical significance.
Aged↗
Diabetic patients with prior specialist care have better glycaemic control than those with prior primary care.
OBJECTIVE: To compare glycaemic control, as reflected in the A1c level, of diabetic patients with primary care vs. with specialist care. METHODS: The study used administrative data from eastern Ontario, Canada, and a database containing the results of all A1c tests from this region between 1 September 1999 and 1 September 2000. To avoid referral bias, diabetic patients with an index specialist visit were selected and separated into those with exclusively primary care previously (n = 974) and those with prior specialist care (n = 3533). We compared A1c levels measured within 30 days of the index visit and hence attributable to the prior care. To control for confounding between the groups, both multiple linear regression and propensity score-based matching were used. RESULTS: After controlling for confounders, patients with prior specialist care had significantly lower A1c levels (P < 0.0001). Other predictors of lower A1c included older age, shorter diabetes duration, rural residence and higher neighbourhood income. In propensity score-matched cohorts, the A1c level was 8.3 +/- 2.0% with prior primary care vs. 7.9 +/- 1.6% with prior specialist care (P < 0.0001). CONCLUSIONS: Specialist care prior to the index visit was associated with a lower A1c level than prior primary care. This difference would result in reductions in diabetes complications for patients with ongoing specialist care.
Aged↗
Diagnostic imaging in Canada.
In Ontario, between 1993 and 2003, the annual number of MRI scans performed increased by more than 600 percent (Iron et al. 2003), and the number of CT scans increased threefold (Tu et al. 2005). Despite these massive increases, the Fraser Institute reported a median wait of five weeks for CT and thirteen weeks for MRI scanning in 2004 (Esmail and Walker 2004), and Canadians are increasingly concerned about the length of time they wait for diagnostic imaging. Because of this, politicians have made decreasing wait times for diagnostic imaging one of their top priorities (Health Canada 2004). This raises several interesting questions. Have the indications for CT and MRI really expanded that rapidly, or was there just a huge pent-up demand because Canada had fallen so far behind in acquiring modern imaging machines? Are physicians relying more on diagnostic imaging technologies and less on clinical skills? Are an increasing number of patients undergoing scans when there is a small likelihood that the results will change their management or improve their outcomes? Supporters of the view that Canada needs to expand its diagnostic imaging capacity point to the fact that we rank well behind many developed countries in terms of the number of diagnostic imaging machines per population (Canadian Institute for Health Information 2003: 33), and that improvements in imaging quality have expanded the indication for imaging. Supporters of the view that there is an increased and inappropriate reliance on technology over clinical skill point to the findings of a recent American study showing that the regions that spent the most on healthcare did not have better outcomes than the regions that spent less--indeed, the trend was toward poorer outcomes in the highest-spending regions (Fisher et al. 2003a, 2003b). One of the greatest differences between the highest- and lowest-spending regions was their expenditure on a variety of diagnostic tests, suggesting that more testing did not lead to better outcomes on a population basis. It may in fact have led to iatrogenic illnesses because of the workup of false positive results, and diverted attention away from simple interventions that have been shown to be effective (Fisher et al. 2003a). The truth is likely a combination of many factors. Some patients with clear indications for diagnostic imaging undoubtedly wait too long for their tests in Canada. At the same time, a number of patients undergo tests whose results have a very small likelihood of changing their management, which itself contributes to the access problem. Unfortunately there are no evidence-based benchmarks for the appropriate rate of diagnostic testing that can be used to determine the optimal supply of diagnostic machines and radiological personnel. In this article we discuss the reasons it has been so difficult to determine the optimal imaging capacity needed for a population, describe some factors that are "inappropriately" increasing the rate of imaging and suggest some solutions. Although many of our examples deal with CT and MRI scanning, our remarks apply more broadly to many other diagnostic tests.
Attitude of Health Personnel↗
Clinical inertia in response to inadequate glycemic control: do specialists differ from primary care physicians?
OBJECTIVE: Diabetic patients with inadequate glycemic control ought to have their management intensified. Failure to do so can be termed "clinical inertia." Because data suggest that specialist care results in better control than primary care, we evaluated whether specialists demonstrated less clinical inertia than primary care physicians. RESEARCH DESIGN AND METHODS: Using administrative data, we studied all non-insulin-requiring diabetic patients in eastern Ontario aged 65 or older who had A1c results >8% between September 1999 and August 2000. Drug intensification was measured by comparing glucose-lowering drug regimens in 4-month blocks before and after the elevated A1c test and was defined as 1) the addition of a new oral drug, 2) a dose increase of an existing oral drug, or 3) the initiation of insulin. Propensity score-based matching was used to control for confounding between groups. RESULTS: There were 591 patients with specialist care and 1,911 with exclusively primary care. In the matched cohorts, 45.1% of patients with specialist care versus 37.4% with primary care had drug intensification (P = 0.009). Most of this difference was attributed to specialists' more frequent initiation of insulin in response to elevated A1c. CONCLUSIONS: Fewer than one-half of patients with high A1c levels had intensification of their medications, regardless of specialty of their physician. Specialists were more aggressive with insulin initiation than primary care physicians, which may contribute to the lower A1c levels seen with specialist care. Interventions assisting patients and physicians to recognize and overcome clinical inertia should improve diabetes care in the population.
Aged↗
Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study.
BACKGROUND: The Randomized Aldactone Evaluation Study (RALES) demonstrated that spironolactone significantly improves outcomes in patients with severe heart failure. Use of angiotensin-converting-enzyme (ACE) inhibitors is also indicated in these patients. However, life-threatening hyperkalemia can occur when these drugs are used together. METHODS: We conducted a population-based time-series analysis to examine trends in the rate of spironolactone prescriptions and the rate of hospitalization for hyperkalemia in ambulatory patients before and after the publication of RALES. We linked prescription-claims data and hospital-admission records for more than 1.3 million adults 66 years of age or older in Ontario, Canada, for the period from 1994 through 2001. RESULTS: Among patients treated with ACE inhibitors who had recently been hospitalized for heart failure, the spironolactone-prescription rate was 34 per 1000 patients in 1994, and it increased immediately after the publication of RALES, to 149 per 1000 patients by late 2001 (P<0.001). The rate of hospitalization for hyperkalemia rose from 2.4 per 1000 patients in 1994 to 11.0 per 1000 patients in 2001 (P<0.001), and the associated mortality rose from 0.3 per 1000 to 2.0 per 1000 patients (P<0.001). As compared with expected numbers of events, there were 560 (95 percent confidence interval, 285 to 754) additional hyperkalemia-related hospitalizations and 73 (95 percent confidence interval, 27 to 120) additional hospital deaths during 2001 among older patients with heart failure who were treated with ACE inhibitors in Ontario. Publication of RALES was not associated with significant decreases in the rates of readmission for heart failure or death from all causes. CONCLUSIONS: The publication of RALES was associated with abrupt increases in the rate of prescriptions for spironolactone and in hyperkalemia-associated morbidity and mortality. Closer laboratory monitoring and more judicious use of spironolactone may reduce the occurrence of this complication.
Adrenergic beta-Antagonists↗
Observational studies of treatment effectiveness: some cautions.
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Coronary Disease↗
Cyclo-oxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients: a population-based cohort study.
BACKGROUND: Non-selective, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of congestive heart failure, but little is known about the cardiovascular effects of a newer group of NSAIDS called selective cyclo-oxygenase (COX)-2 inhibitors. We aimed to compare rates of admission for congestive heart failure in elderly patients who were newly dispensed COX-2 inhibitors or non-selective NSAIDs. METHODS: In this population-based retrospective cohort study we identified NSAID-naive individuals aged 66 years or older, who were started on rofecoxib (n=14,583), celecoxib (n=18,908), and non-selective NSAIDs (n=5,391), and randomly selected non-NSAID users as controls (n=100,000). FINDINGS: Relative to non-NSAID users, patients on rofecoxib and non-selective NSAIDS had an increased risk of admission for congestive heart failure (adjusted rate ratio 1.8, 95% CI 1.5-2.2, and 1.4, 1.0-1.9, respectively), but not celecoxib (1.0, 0.8-1.3). Compared with celecoxib users, admission was significantly more likely in users of non-selective NSAIDs (1.4, 1.0-1.9) and rofecoxib (1.8, 1.4-2.4). Risk of admission for rofecoxib users was higher than that for non-selective NSAID users (1.5, 1.1-2.1). Of patients with no admission in the past 3 years, only rofecoxib users were at increased risk of subsequent admission relative to controls (1.8, 1.4-2.3). INTERPRETATION: These findings suggest a higher risk of admission for congestive heart failure in users of rofecoxib and non-selective NSAIDs, but not celecoxib, relative to non-NSAID controls.
Aged↗
Stroke care delivery in institutions participating in the Registry of the Canadian Stroke Network.
BACKGROUND AND PURPOSE: Guidelines and performance indicators have been established for acute stroke care. However, little is known about the process of stroke care delivery in Canada. METHODS: The Registry of the Canadian Stroke Network (RCSN) captured detailed clinical data on patients with stroke and transient ischemic attack seen at 21 acute care institutions across Canada. Data from phase 1 of the RCSN (June 2001 to February 2002) were used to determine the use of evidence-based acute stroke care interventions in participating institutions. RESULTS: Overall, 4439 patients were seen during the study time frame and 1701 (38%) consented to full data collection. Thirty-one percent received care on a stroke unit or from a mobile stroke team. Among patients with ischemic stroke, 7% received thrombolysis, 80% underwent carotid imaging, 89% received antithrombotic agents, and 54% of those with atrial fibrillation received warfarin. There were significant intersite variations in the delivery of all of these interventions except for the use of antithrombotic agents, and these persisted after adjustment for age, sex, stroke type, and other comorbid conditions. CONCLUSIONS: Patients in institutions participating in the RCSN received high-quality stroke care based on a number of performance measures. However, gaps exist in the provision of other elements of stroke care, particularly organized inpatient stroke care and warfarin for atrial fibrillation. Future research should explore explanations for these findings and focus on solutions to deficiencies in care.
Aged↗
Gastrointestinal bleeding after the introduction of COX 2 inhibitors: ecological study.
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Age Factors↗
Age, risk-benefit trade-offs, and the projected effects of evidence-based therapies.
BACKGROUND: Physicians underutilize evidence-based therapies in the elderly, perhaps because of concerns about the generalizability of clinical trial results in elderly patients given that the relative efficacy of therapies may vary with age. We compared the estimated effects of age and efficacy of treatment on survival among patients with acute coronary syndromes. METHODS: Baseline risk, defined as mortality in the year after hospitalization for acute coronary syndromes, was determined for different age strata among 81,584 patients who had been discharged between April 1, 1997, and March 31, 2000, in Ontario, Canada. We calculated the relative efficacy (relative risk reduction) needed to achieve a clinically meaningful absolute survival benefit, using a number needed to treat of 50 patients for the different age strata. We also evaluated risk-benefit trade-offs in the elderly versus the young by modeling different levels of the relative efficacy and rates of fatal complication by age. RESULTS: Baseline risk (1-year all-cause mortality) was 12-fold lower in the youngest patients (age <50 years) than in oldest patients (age > or = 75 years). Given this gradient, a therapy would have to have a relative efficacy of 88% (i.e., a relative risk of 0.12) in the youngest age group, and 7% (a relative risk of 0.93) in the oldest age group, to generate a number needed to treat 50 patients. For a therapy whose relative efficacy was 25%, the fatal complication rate would have to be sevenfold greater in the oldest compared with the youngest age group to outweigh the survival benefits associated with treatment. CONCLUSION: For acute coronary syndromes, baseline mortality is so much higher for elderly patients that neither sharp reductions in the relative efficacy of therapies nor increases in the rates of serious complications are likely to negate the benefits of therapy. More attention should be paid to overall trial results and less to age-specific subgroup data, unless the latter provide very clear evidence for substantial reductions in absolute efficacy or net harm.
Aged↗
Impracticability of informed consent in the Registry of the Canadian Stroke Network.
BACKGROUND: Government legislators and research ethics boards in some jurisdictions require all patients to give written informed consent before enrollment in clinical registries. However, the effect of such a requirement on the use of clinical registries and the extent to which registry data can be generalized remain uncertain. METHODS: We examined the effectiveness of a comprehensive attempt to obtain informed consent between June 2001 and December 2002 on the overall participation rate and the characteristics of participating patients in the Registry of the Canadian Stroke Network, a prospective registry based at 20 major stroke centers across Canada. RESULTS: The overall participation rate (i.e., the consent rate among all potential participants) was 39.3 percent of 4285 eligible patients during phase 1 of the project (June 2001 through February 2002) and 50.6 percent of 2823 eligible patients during phase 2 (June 2002 through December 2002), despite the presence of neurologic research nurse coordinators at each site. Many patients died or left the hospital before they could be approached for consent. Major selection biases were found; the in-hospital mortality rate was much lower among patients who were enrolled (6.9 percent) than among those who were not enrolled (21.7 percent) (relative risk of in-hospital death, 3.13; 95 percent confidence interval, 2.65 to 3.70; P<0.001). We estimate that approximately 500,000 dollars (Canadian dollars) was spent on consent-related issues during the first two years of the registry. CONCLUSIONS: Obtaining written informed consent for participation in a stroke registry led to important selection biases, such that registry patients were not representative of the typical patient with stroke at each center. These findings highlight the need for legislation on privacy and policies permitting waivers of informed consent for minimal-risk observational research.
Canada↗
Management and outcomes of transient ischemic attacks in Ontario.
BACKGROUND: Canadian data on the characteristics, management and outcomes of patients with transient ischemic attack (TIA) are lacking. We studied prospectively a cohort of consecutive patients presenting with TIA to the emergency department of 4 regional stroke centres in Ontario. METHODS: Using data from the Ontario Stroke Registry linked with provincial administrative databases, we determined the short-term outcomes after TIA and assessed patient management in the emergency department and within 30 days after the index TIA. We compared the TIA patients with a cohort of patients who had ischemic stroke. RESULTS: Three-quarters of the TIA patients were discharged from the emergency department. After discharge, the 30-day stroke risk was 5% (13/265) overall and 8% (13/167) among those with a first-ever TIA; the 30-day risk of stroke or death was 9% (11/127) among the TIA patients with a speech deficit and 12% (9/76) among those with a motor deficit. Half of the cases of stroke occurred within the first 2 days after the TIA. Diagnostic investigations were underused in hospital and on an outpatient basis within 30 days after the index TIA, the rates being as follows: CT scanning, 58% (211/364); carotid Doppler ultrasonography, 44% (162/364); echocardiography, 19% (70/364); cerebral angiography, 5% (19/364); and MRI, 3% (11/364). Antithrombotic therapy was not prescribed for more than one-third of the patients at discharge. Carotid endarterectomy was performed in 2% within 90 days. INTERPRETATION: Patients in whom TIA is diagnosed in the emergency department have high immediate and short-term risks of stroke. However, their condition is underinvestigated and undertreated compared with stroke: many do not receive the minimum recommended diagnostic tests within 30 days. We need greater efforts to improve the timely delivery of care for TIA patients, along with investigation of treatments administered early after TIA to prevent stroke.
Adrenergic beta-Antagonists↗