Geoffrey M. Anderson

Do practice guidelines guide practice? The effect of a consensus statement on the practice of physicians.

Guidelines for medical practice can contribute to improved care only if they succeed in moving actual practice closer to the behaviors the guidelines recommend. To assess the effect of such guidelines, we surveyed hospitals and obstetricians in Ontario before and after the release of a widely distributed and nationally endorsed consensus statement recommending decreases in the use of cesarean sections. These surveys, along with discharge data from hospitals reflecting actual practice, revealed that most obstetricians (87 to 94 percent) were aware of the guidelines and that most (82.5 to 85 percent) agreed with them. Attitudes toward the use of cesarean section were congruent with the recommendations even before their release. One third of the hospitals and obstetricians reported changing their practice as a consequence of the guidelines, and obstetricians reported rates of cesarean section in women with a previous cesarean section that were significantly reduced, in keeping with the recommendations (from 72.2 percent to 61.1 percent; P less than 0.01). The surveys also showed, however, that knowledge of the content of the recommendations was poor (67 percent correct responses). Furthermore, data on actual practice after the publication of the guidelines showed that the rates of cesarean section were 15 to 49 percent higher than the rates reported by obstetricians, and they showed only a slight change from the previous upward trend. We conclude that guidelines for practice may predispose physicians to consider changing their behavior, but that unless there are other incentives or the removal of disincentives, guidelines may be unlikely to effect rapid change in actual practice. We believe that incentives should operate at the local level, although they may include system-wide economic changes.

Antipsychotic Drug Use and Mortality in Older Adults with Dementia

Context Recent reports suggest that antipsychotics are associated with increased risk for death in patients with dementia. Contribution This large, population-based study from Canada assessed the risk for death after dispensation of antipsychotics in older adults with dementia. New use of antipsychotics compared with nonuse was associated with increased risk for death at 30 days. Conventional agents were associated with higher risks than were atypical agents. Caution Sensitivity analyses showed that unmeasured confounders might diminish or erase observed associations. Implication Both conventional and atypical antipsychotics may be associated with an increased risk for death in elderly persons with dementia. The Editors Various challenging behavioral and psychological symptoms commonly develop in older adults with dementia and predispose them and their caregivers to poor outcomes (1). Nonpharmacologic strategies are recommended as first-line management for these symptoms (2), but they may be difficult to implement in clinical practice (3). For many reasons, antipsychotic medications are routinely prescribed in this setting (4, 5). Conventional antipsychotics, such as haloperidol, have been available since the 1950s. Meta-analyses of clinical trials evaluating conventional antipsychotics to treat agitation in dementia show that these agents have modest efficacy and important adverse effects compared with placebo (6, 7). In the past decade, use of newer atypical antipsychotics has been rapidly increasing in clinical practice because these agents were thought to produce fewer adverse effects than conventional agents (2). A Canadian study found that the prevalence of antipsychotic use in older adults increased from 2.2% in 1993 to 3.0% at the end of 2002. In that study, atypical antipsychotics, which were unavailable in 1993, accounted for 82.5% of all antipsychotics dispensed in 2002 (8). Short-term randomized, controlled trials (RCTs) have studied the role of atypical antipsychotics in the management of behavioral and psychological symptoms of dementia (2, 9). An RCT involving 421 outpatients with Alzheimer disease and psychosis, aggression, or agitation concluded that the adverse effects of these newer drugs offset their advantages (10). As a result, improvements in behavioral symptoms with antipsychotic drug treatment do not necessarily lead to improvements in overall quality of life for patients or their caregivers (11). In April 2005, the U.S. Food and Drug Administration (FDA) issued a public health advisory that the use of atypical antipsychotics to treat elderly patients with dementia was associated with an increased risk for death compared with placebo (12). In June 2005, Health Canada issued a similar warning and additional data (13). These warnings stem from reviews of RCTs that involve the atypical agents risperidone, olanzapine, quetiapine, and aripiprazole. The mortality rate was approximately 1.6 to 1.7 times higher than with placebo and was greater with antipsychotics than with placebo in 15 of the 17 trials reviewed by the U.S. FDA (12). The warnings extend to all currently available atypical antipsychotics. Other publications have provided support for these warnings and have raised further safety concerns about older conventional antipsychotics (1416). Important questions remain unanswered. Although RCTs provide the best evidence of treatment efficacy and harm, the individual RCTs in this case had low event rates. Reliable estimates of the mortality risk were generated only when data were combined by meta-analysis (14). Furthermore, these RCTs were generally short in duration and could not provide information about the long-term effect of antipsychotics on mortality (14, 17). Finally, these trials provide estimates of harm primarily for atypical antipsychotics. Relatively few data are available on harms associated with older conventional antipsychotics. Studies suggest that important differences may exist in the safety profiles of conventional and atypical agents (15, 16, 18, 19). Using population-based data, we sought to determine the risk for all-cause mortality in older adults with dementia who received atypical antipsychotics, conventional antipsychotics, or no antipsychotic. Because important baseline differences exist among these groups, we used propensity score matching to improve their comparability. We also evaluated the effect of duration of treatment with antipsychotics on the risk for death. Methods Data Sources Ontario is Canadas most populous province. During our study, Ontario had a population of approximately 12 million people, of whom 1.4 million were 65 years of age or older. A universally funded health program covers nearly all physician services, medications, and hospital services for patients 65 years of age or older in Ontario. Information from 4 administrative health care databases was linked to develop the study cohort: pharmacy records from the Ontario Drug Benefit program, hospitalization records from the Canadian Institute for Health Information Discharge Abstract Database, physician billing information for inpatient and outpatient services from the Ontario Health Insurance Plan, and basic demographic information and vital statistics from the Registered Persons Database. We used encrypted unique identifiers that are common among databases to link anonymous information on demographic characteristics and health services utilization for patients in our study. Little basic information on patients is missing in these databases. For example, the coding accuracy of drug claims in the Ontario Drug Benefit program database is excellent, with an error rate of only 0.7% (20). The study was approved by the ethics review board of Sunnybrook and Womens College Health Sciences Centre, Toronto, Ontario, Canada. Dementia Cohort We identified a cohort of all Ontario residents 66 years of age or older with a diagnosis of dementia (in the Ontario Health Insurance Plan or Discharge Abstract Database) between 1 April 1997 and 31 March 2002. To focus on antipsychotic drug treatment for behavioral and psychological symptoms of dementia, we excluded patients who had evidence of other psychotic disorders (such as schizophrenia) or were receiving palliative care services. To reduce the potential for selection bias, we studied only new users of antipsychotics and excluded those who had received antipsychotics in the year before cohort entry (21). Exposure to Antipsychotics We identified new use of antipsychotics if any agent available through the Ontario Drug Benefit program was dispensed after cohort entry. Cohort entry (that is, the index date) was defined as the date of the first dispensed antipsychotic drug. Available atypical drugs included olanzapine, quetiapine, and risperidone, and available conventional drugs included chlorpromazine, flupenthixol, fluphenazine, haloperidol, loxapine, pericyazine, perphenazine, pimozide, thioridazine, and trifluoperazine. Clozapine was rarely used in Ontario during the study period, and we therefore excluded patients who were receiving this medication. Other atypical antipsychotics (such as aripiprazole and ziprasidone) are not licensed for use in Canada. We decided that exposure to an antipsychotic was discontinued (and we censored follow-up) if the patient did not refill his or her antipsychotic prescription within an interval composed of the days of drug supply plus a grace period of 20%. For example, we censored follow-up for a patient who did not refill his or her 60-day antipsychotic prescription within 72 days. We also censored follow-up for patients who switched from atypical to conventional antipsychotics (or vice versa). However, we continued follow-up for patients who switched from 1 atypical antipsychotic to another, because data suggest no statistically significant difference in the risk for death associated with individual drugs in this class (13, 14, 16). We applied the same rules to conventional antipsychotics. All-Cause Mortality The primary outcome was all-cause mortality, as recorded in the Registered Persons Database (for patients who were not hospitalized at the time of death) or the Discharge Abstract Database (for patients who died while hospitalized). To assess the influence of the duration of antipsychotic exposure on the outcome, we evaluated the risk for death at 30, 60, 120, and 180 days after the initial dispensing of antipsychotic medication. Cohort Matching We stratified the dementia cohort to support separate analyses among persons living in the community and those residing in long-term care at cohort entry. Studies have demonstrated that rates of antipsychotic prescribing are substantial among older adults newly admitted to long-term care facilities (4). Furthermore, long-term care residents typically carry a greater burden of comorbid disease and are more vulnerable to adverse drug events than are their counterparts in the community (22, 23). Our first objective was to determine the risk for death among older adults with dementia who received atypical antipsychotics compared with those who were not exposed to any antipsychotic. Because antipsychotic use was not randomly assigned in the study cohorts, we addressed potential confounding and selection biases by developing a propensity score for antipsychotic use. We then applied this score to match users of atypical antipsychotics with nonusers in the dementia cohort. The rationale and methods underlying the use of a propensity score for a proposed causal exposure variable are described elsewhere (24). Recent studies provide guidance on the selection of variables to include in the propensity score (25, 26). We developed a logistic regression model by using 42 covariates describing patient characteristics. Tables 1 and 2 list many of the characteristics included in the propensity score. After a structured and iterative assessment of the balance of measured covariates betwe

Reader's guide to critical appraisal of cohort studies: 2. Assessing potential for confounding

Although confounding is an important problem of cohort studies, its effects can be minimised to enable valid comparison In cohort studies, who does or does not receive an intervention is determined by practice patterns, personal choice, or policy decisions. This raises the possibility that the intervention and comparison groups may differ in characteristics that affect the study outcome, a problem called selection bias. If these characteristics have independent effects on the observed outcome in each group, they will create differences in outcomes between the groups apart from those related to the interventions being assessed. This effect is known as confounding.1 In the first paper in the series we dealt with the design and use of cohort studies and how to identify selection bias.2 This paper focuses on the definition and assessment of confounders. For a characteristic to be a confounder in a particular study, it must meet two criteria.1 The first is that it must be related to the outcome in terms of prognosis or susceptibility. For example, in the study of the association between antipsychotic use and hip fracture that we considered in the first paper,2 age is known to be related to risk of hip fracture and therefore has the potential to be a confounder. The second criterion that defines a confounder is that the distribution of the characteristic is different in the groups being compared. It can differ in terms of either the mean or the degree of variation or variability in that characteristic. For example, for age to be a confounder in a cohort study, either the average age or the variation in the age in the groups being compared would have to be different. Assessing variation as well as average values is important because groups can have the same average value …

Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs

Abstract Objective: To compare rates of upper gastrointestinal haemorrhage among elderly patients given selective cyclo-oxygenase-2 (COX 2) inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs). Design: Observational cohort study. Setting: Administrative data from Ontario, Canada, used from 17 April 2000 to 31 March 2001 to identify population based, NSAID-naive cohorts of patients. Patients: Subjects aged ≥ 66 years who started taking non-selective NSAIDs (n=5391), diclofenac plus misoprostol (n=5087), rofecoxib (n=14 583), or celecoxib (n=18 908) and a randomly selected control cohort not exposed to NSAIDs (n=100 000). Main outcome measures: Rate ratios of hospital admission for upper gastrointestinal haemorrhage in each drug cohort with adjustment for potential confounders. Results: Relative to controls, the multivariate model revealed an increased short term risk of upper gastrointestinal haemorrhage for users of non-selective NSAIDs (adjusted rate ratio 4.0 (95% confidence intervals 2.3 to 6.9)), diclofenac plus misoprostol (3.0 (1.7 to 5.6)), and rofecoxib (1.9 (1.3 to 2.8)) but not celecoxib (1.0 (0.7 to 1.6)). Relative to celecoxib, significantly higher risks of upper gastrointestinal haemorrhage were observed for non-selective NSAIDs (4.4 (2.3 to 8.5)), diclofenac plus misoprostol (3.2 (1.6 to 6.5)), and rofecoxib (1.9 (1.2 to 2.8)). Relative to rofecoxib, non-selective NSAID users were at significantly higher risk of upper gastrointestinal haemorrhage (1.9 (1.0 to 3.5)). Conclusions: This population based observational study found a lower short term risk of upper gastrointestinal haemorrhage for selective COX-2 inhibitors compared with non-selective NSAIDs.

Assessing the clinical effectiveness of preventive maneuvers: analytic principles and systematic methods in reviewing evidence and developing clinical practice recommendations. A report by the Canadian Task Force on the Periodic Health Examination.

This paper examines a process for evaluating clinical effectiveness and developing recommendations in which systematic methods are used to review evidence from published clinical research and to reach sound conclusions about appropriate medical policy. The methodology addresses four important components of the analytic process: (1) the criteria that must be satisfied for a clinical practice to be considered effective; (2) proper methods for reviewing evidence from published clinical research to determine whether a clinical practice meets these criteria (including methods for performing comprehensive literature reviews, for judging the quality of individual studies, and for synthesizing or pooling the results of multiple studies); (3) theoretical and practical concerns in translating the results of the scientific review into sound clinical practice recommendations; and (4) the importance of documentation, guidelines, and other safeguards to minimize the effect the reviewers themselves have on the objectivity and consistency of the analytic methods.

Revisiting Rose: strategies for reducing coronary heart disease

The way we assess risk of coronary heart disease has become more accurate in recent years. How does this affect the efficacy of primary and secondary prevention strategies?

Nursing Home Profit Status and Quality of Care: Is There Any Evidence of an Association?

This article critically reviews the association between the profit status of North American nursing homes and the quality of care. Studies were identified by searching MEDLINE (January 1990-October 2002), reference lists, letters, commentaries, and editorials. The quality indicator(s) used to measure quality of care, and its relationship to profit status, was extracted from each publication. The study design and risk-adjustment methodologies used were also extracted. The interrater reliability for the extraction of these three items was determined to be 1.0, 0.6, and 0.8, respectively. Aqualitative systematic review was performed using Donabedian’s framework of structure, process, and outcome for analyzing medical quality of care. Empirical research in the past 12 years has found that systematic differences exist between for-profit and not-for-profit nursing homes. Forprofit nursing homes appear to provide lower quality of care in many important areas of process and outcome.

Antipsychotic therapy and short-term serious events in older adults with dementia.

BACKGROUND Antipsychotic therapy is widely used to treat behavioral problems in older adults with dementia. Cohort studies evaluating the safety of antipsychotic therapy generally focus on a single adverse event. We compared the rate of developing any serious event, a composite outcome defined as an event serious enough to lead to an acute care hospital admission or death within 30 days of initiating antipsychotic therapy, to better estimate the overall burden of short-term harm associated with these agents. METHODS In this population-based, retrospective cohort study, we identified 20 682 matched older adults with dementia living in the community and 20 559 matched individuals living in a nursing home between April 1, 1997, and March 31, 2004. Propensity-based matching was used to balance differences between the drug exposure groups in each setting. To examine the effects of antipsychotic drug use on the composite outcome of any serious event we used a conditional logistic regression model. We also estimated adjusted odds ratios using models that included all covariates with a standard difference greater than 0.10. RESULTS Relative to those who received no antipsychotic therapy, community-dwelling older adults newly dispensed an atypical antipsychotic therapy were 3.2 times more likely (95% confidence interval, 2.77-3.68) and those who received conventional antipsychotic therapy were 3.8 times more likely (95% confidence interval, 3.31-4.39) to develop any serious event during the 30 days of follow-up. The pattern of serious events was similar but less pronounced among older adults living in a nursing home. CONCLUSIONS Serious events, as indicated by a hospital admission or death, are frequent following the short-term use of antipsychotic drugs in older adults with dementia. Antipsychotic drugs should be used with caution even when short-term therapy is being prescribed.

Reader's guide to critical appraisal of cohort studies: 1. Role and design

Cohort studies can provide valuable information unavailable from randomised trials, but readers need to be alert to possible flaws

Determinants of the increasing cesarean birth rate. Ontario data 1979 to 1982.

We analyzed the records of 454,668 births in Ontario in the years 1979 to 1982 and found that the cesarean birth rate increased from 16.5 per hundred deliveries in 1979 to 18.7 in 1982. Cesarean births were classified according to four indications: previous cesarean birth, breech presentation, dystocia, and fetal distress. The increase in the cesarean rate for each indication from 1979 to 1982 was calculated and expressed as a percentage of the total rate increase. Previous cesarean births accounted for 68 per cent of the increase, breech presentation for 14 per cent, dystocia for 4 per cent, and fetal distress for 14 per cent. The impact of previous cesarean births was indicated by an increase in the number of women presenting with this indication--from 5.8 to 7.8 per cent of all deliveries. Although the incidence of breech presentation remained stable, the cesarean birth rate increased from 54.8 to 65 per cent for this indication. There were no marked changes in either the incidence of or cesarean rates for dystocia. The incidence of fetal distress doubled (2.4 to 4.7 per cent of deliveries), but the rate of cesarean births in these cases fell from 50.5 to 32.7 per cent. These findings suggest that physicians may have begun to respond to rising professional and public concern over the increasing cesarean birth rate, but major advances in controlling this rate can be achieved only by addressing the question of vaginal deliveries for some patients who have previously had cesarean section.