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Biomedical subjects

David N Juurlink

Publications and source records attributed to David N Juurlink.

At least 19 recordsLinked to original sources
PubMed2006

Testing multiple statistical hypotheses resulted in spurious associations: a study of astrological signs and health.

OBJECTIVES: To illustrate how multiple hypotheses testing can produce associations with no clinical plausibility. STUDY DESIGN AND SETTING: We conducted a study of all 10,674,945 residents of Ontario aged between 18 and 100 years in 2000. Residents were randomly assigned to equally sized derivation and validation cohorts and classified according to their astrological sign. Using the derivation cohort, we searched through 223 of the most common diagnoses for hospitalization until we identified two for which subjects born under one astrological sign had a significantly higher probability of hospitalization compared to subjects born under the remaining signs combined (P<0.05). RESULTS: We tested these 24 associations in the independent validation cohort. Residents born under Leo had a higher probability of gastrointestinal hemorrhage (P=0.0447), while Sagittarians had a higher probability of humerus fracture (P=0.0123) compared to all other signs combined. After adjusting the significance level to account for multiple comparisons, none of the identified associations remained significant in either the derivation or validation cohort. CONCLUSIONS: Our analyses illustrate how the testing of multiple, non-prespecified hypotheses increases the likelihood of detecting implausible associations. Our findings have important implications for the analysis and interpretation of clinical studies.

Adolescent↗
PubMed2006

How many "Me-Too" drugs are enough? The case of physician preferences for specific statins.

BACKGROUND: The increasing availability of "Me-Too" drugs has provided considerable treatment options for clinicians. However, the number of such drugs within a class that are actually used by clinicians has not been well studied. OBJECTIVE: To determine the number of different statins that individual physicians use in practice. METHODS: The Ontario Drug Benefit database was used to identify physicians who issued at least 10 incident statin prescriptions between October 2001 and May 2003 for patients aged 66 years and older. A preferred statin was defined for each physician, and the proportion of each physician's incident prescriptions written for that agent was determined. We then determined the number of different statins required to fill each physician's incident prescribing needs. RESULTS: A total of 3426 physicians wrote 73,571 incident statin prescriptions. The mean percentage of prescriptions written for each physician's preferred statin formulation was 73.7%. Repeat analysis to examine the proportion of prescriptions filled using each physician's top 2 statin formulations found that the average physician wrote the vast majority of his or her incident prescriptions (94.9%) for only 1 or 2 statins. Half of all physicians used, at most, 2 different statins for all incident prescribing, while 91.3% of physicians used, at most, 3 different statins for all of their incident prescribing. CONCLUSIONS: A high proportion of Ontario physicians issued the majority of their incident statin prescriptions for the same statin formulation. Most physicians required, at most, 3 different statins for all incident statin prescribing.

Adult↗
PubMed2006

Outpatient gatifloxacin therapy and dysglycemia in older adults.

BACKGROUND: Gatifloxacin has been associated with both hypoglycemia and hyperglycemia. We examined dysglycemia-related health outcomes associated with various antibiotics in a population of approximately 1.4 million Ontario, Canada, residents 66 years of age or older. METHODS: We conducted two population-based, nested case-control studies. In the first, case patients were persons treated in the hospital for hypoglycemia after outpatient treatment with a macrolide, a second-generation cephalosporin, or a respiratory fluoroquinolone (gatifloxacin, levofloxacin, moxifloxacin, or ciprofloxacin). In the second, case patients were persons who received hospital care for hyperglycemia. For each case patient, we identified up to five controls matched according to age, sex, the presence or absence of diabetes, and the timing of antibiotic therapy. RESULTS: Between April 2002 and March 2004, we identified 788 patients treated for hypoglycemia within 30 days after antibiotic therapy. As compared with macrolide antibiotics, gatifloxacin was associated with an increased risk of hypoglycemia (adjusted odds ratio, 4.3; 95 percent confidence interval, 2.9 to 6.3). Levofloxacin was also associated with a slightly increased risk (adjusted odds ratio, 1.5; 95 percent confidence interval, 1.2 to 2.0), but no such risk was seen with moxifloxacin, ciprofloxacin, or cephalosporins. We then identified 470 patients treated for hyperglycemia within 30 days after antibiotic therapy. As compared with macrolides, gatifloxacin was associated with a considerably increased risk of hyperglycemia (adjusted odds ratio, 16.7; 95 percent confidence interval, 10.4 to 26.8), but no risk was noted with the other antibiotics. Risks were similar in the two studies regardless of the presence or absence of diabetes. CONCLUSIONS: As compared with the use of other broad-spectrum oral antibiotics, including other fluoroquinolones, the use of gatifloxacin among outpatients is associated with an increased risk of in-hospital treatment for both hypoglycemia and hyperglycemia.

Aged↗
PubMed2006

Missed opportunities in the secondary prevention of myocardial infarction: an assessment of the effects of statin underprescribing on mortality.

BACKGROUND: The benefits of statins for the secondary prevention of coronary heart disease are well established. Previous research indicates that patients at the greatest risk of cardiovascular events are the least likely to receive statins. We explored the potential reduction in mortality at the population level that could result from improving statin prescribing among patients least likely to be prescribed a statin after acute myocardial infarction (AMI). METHODS: Simulation analysis of detailed clinical data for a population-based sample of 7285 AMI survivors discharged from 102 hospitals between April 1, 1999, and March 31, 2001 in Ontario, Canada, was done. Using estimates obtained from randomized controlled trials, we estimated the reduction in 3-year all-cause mortality associated with improved statin prescribing at hospital discharge. RESULTS: Overall, 35.6% of patients received a statin prescription at hospital discharge. We estimate that increasing statin prescribing among patients least likely to receive them (ie, the lowest quintile of propensity to receive a prescription at discharge) from the current rate of 7.8% to the rate among all patients (35.6%) could decrease AMI mortality by 83 deaths in Ontario per year (2.1% of all post-AMI deaths within 3 years of discharge). Increasing statin prescribing to 70% among all patients with AMI could avert 312 deaths per year in Ontario. Factoring in low rates of adherence to statin therapy would reduce these estimates to 33 and 126, respectively. CONCLUSIONS: Modest increases in statin prescribing for patients least likely to receive one could decrease post-AMI mortality at the population level.

Aged↗
PubMed2006

Appropriateness of spironolactone prescribing in heart failure patients: a population-based study.

BACKGROUND: The Randomized Aldactone Evaluation Study (RALES) established the safety and benefit of spironolactone for heart failure (HF) patients with systolic dysfunction. However, recent data have raised concerns regarding hyperkalemia secondary to spironolactone use and suggest it occurs more commonly in routine practice. METHODS AND RESULTS: We explored factors potentially associated with hyperkalemia from spironolactone therapy in a population-based cohort of 9165 HF patients hospitalized in Ontario, Canada, between 1999 and 2001. Compared with patients enrolled in RALES, community-based patients were older (mean age 75 years versus 65 years, P < .001) and were more likely to be female (50% versus 27%, P < .001). Of the 1502 patients that were prescribed spironolactone at discharge, 18% had elevated serum potassium levels (>5 mmol/L) during hospitalization and 23% were discharged on concurrent potassium supplements. Although only 8% of patients had serum creatinine >2.5 mg/dL, many patients had stage III (53.1%), stage IV (12.8%), or stage V (3.9%) chronic renal insufficiency according to glomerular filtration rate. CONCLUSION: Spironolactone was often prescribed to inappropriate HF candidates because of the presence of relative or absolute contraindications. These findings highlight the need for more careful patient selection when prescribing spironolactone to minimize potential life-threatening hyperkalemia.

Aged↗
PubMed2006

Are broad-spectrum fluoroquinolones more likely to cause Clostridium difficile-associated disease?

Limited evidence suggests that broad-spectrum fluoroquinolones such as gatifloxacin and moxifloxacin are more likely to cause Clostridium difficile-associated disease than levofloxacin. In a population-based case-control study of outpatients prescribed fluoroquinolones, we found no increased risk of C. difficile-associated disease requiring hospitalization among patients prescribed gatifloxacin or moxifloxacin compared to levofloxacin.

Aged↗
PubMed2006

The risk of suicide with selective serotonin reuptake inhibitors in the elderly.

OBJECTIVE: The authors explored the relationship between the initiation of therapy with selective serotonin reuptake inhibitor (SSRI) antidepressants and completed suicide in older patients. METHOD: The authors linked population-based coroner's records with patient-level prescription data, physician billing claims, and hospitalization data for more than 1.2 million Ontario residents 66 years of age and older from 1992 to 2000. For each suicide case, four closely matched comparison subjects were selected using propensity score methods. The authors determined the odds ratio for suicide with SSRIs versus other antidepressant treatment, calculated at discrete monthly intervals from the start of treatment. RESULTS: Of 1,329 suicide cases, 1,138 (86%) were each fully matched to four comparison subjects using propensity scores. During the first month of therapy, SSRI antidepressants were associated with a nearly fivefold higher risk of completed suicide than other antidepressants (adjusted odds ratio: 4.8, 95% confidence interval=1.9-12.2). The risk was independent of a recent diagnosis of depression or the receipt of psychiatric care, and suicides of a violent nature were distinctly more common during SSRI therapy. Numerous sensitivity analyses revealed consistent results. No disproportionate suicide risk was seen during the second and subsequent months of treatment with SSRI antidepressants, and the absolute risk of suicide with all antidepressants was low. CONCLUSIONS: Initiation of SSRI therapy is associated with an increased risk of suicide during the first month of therapy compared with other antidepressants. The absolute risk is low, suggesting that an idiosyncratic response to these agents may provoke suicide in a vulnerable subgroup of patients.

Age Factors↗
PubMed2005

Risk-treatment mismatch in the pharmacotherapy of heart failure.

CONTEXT: Patients with heart failure have a wide spectrum of mortality risks. To maximize the benefit of available pharmacotherapies, patients with high mortality risk should receive high rates of drug therapy. OBJECTIVE: To examine patterns of drug therapy and underlying mortality risk in patients with heart failure. DESIGN, SETTING, AND PATIENTS: In the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) population-based cohort (1999-2001) of 9942 patients with heart failure hospitalized in Ontario, Canada, we evaluated 1418 patients with documented left ventricular ejection fraction of 40% or less and aged 79 years or younger with low-, average-, and high-predicted risk of death within 1 year; all patients survived to hospital discharge. Administration of angiotensin-converting enzyme (ACE) inhibitors, ACE inhibitors or angiotensin II receptor blockers (ARBs), and beta-adrenoreceptor antagonists was evaluated according to predicted risk of death. MAIN OUTCOME MEASURE: Heart failure drug administration rates at time of discharge and 90 days after hospital discharge. RESULTS: At hospital discharge, prescription rates for patients in the low-, average-, and high-risk groups were 81%, 73%, 60%, respectively, for ACE inhibitors; 86%, 80%, 65%, respectively, for ACE inhibitors or ARBs; and 40%, 33%, 24%, respectively, for beta-adrenoreceptor antagonists (all P<.001 for trend). Within 90 days following hospital discharge, the rates were 83%, 76%, and 61% for ACE inhibitors; 89%, 83%, and 67% for ACE inhibitors or ARBs; and 43%, 36%, and 28% for beta-adrenoreceptor antagonists for the 3 risk groups, respectively (all P<.001 for trend). The pattern of lower rates of drug administration in those patients at increasing risk was maintained up to 1 year postdischarge (P<.001). After accounting for varying survival time and potential contraindications to therapy, low-risk patients were more likely to receive ACE inhibitors or ARBs (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.49-1.74) and beta-adrenoreceptor antagonists (HR, 1.80; 95% CI, 1.60-2.01) compared with high-risk patients (both P<.001). CONCLUSIONS: Patients with heart failure at greatest risk of death are least likely to receive ACE inhibitors, ACE inhibitors or ARBs, and beta-adrenoreceptor antagonists. Understanding the reasons underlying this mismatch may facilitate improvements in care and outcomes for patients with heart failure.

Adrenergic beta-Antagonists↗
PubMed2005

Kappa statistic.

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Evidence-Based Medicine↗
PubMed2005

Identifying individuals with a reduced GFR using ambulatory laboratory database surveillance.

The use of outpatient laboratory databases to identify people with a low GFR may be part of an effective strategy to increase their use of treatments to prevent kidney failure. All renal function data from 17 independent outpatient laboratories in Eastern Ontario were combined to determine the proportion of adults with at least one serum creatinine measurement during a 1-yr period. The detection rates of low GFR were measured using different algorithms, and what proportion of identified low GFR was transient was considered. Canadian census data were used to calculate rates and proportions. Renal function testing was common. Of the 1,090,000 adult residents, 32% of the entire population and 63% of seniors had at least one serum creatinine measured during the study year. Sixteen percent of the population (49% of those with tests performed) had at least one GFR <80 ml/min per 1.73 m2, 5% (16%) had at least one GFR <60 ml/min per 1.73 m2, and 0.6% (1.7%) had at least one GFR <30 ml/min per 1.73 m2. Low GFR were usually not transient: 68% of individuals with subsequent testing at least 30 d later had a similar or worse GFR. Ambulatory laboratory database case finding, particularly in older patients, seems to be a promising method for easily identifying large segments of the population with persistent reductions in GFR. Whether such identification leads to improved health outcomes warrants further study.

Algorithms↗
PubMed2005

Unintended medication discrepancies at the time of hospital admission.

BACKGROUND: Prior studies suggest that unintended medication discrepancies that represent errors are common at the time of hospital admission. These errors are particularly worthy of attention because they are not likely to be detected by computerized physician order entry systems. METHODS: We prospectively studied patients reporting the use of at least 4 regular prescription medications who were admitted to general internal medicine clinical teaching units. The primary outcome was unintended discrepancies (errors) between the physicians' admission medication orders and a comprehensive medication history obtained through interview. We also evaluated the potential seriousness of these discrepancies. All discrepancies were reviewed with the medical team to determine if they were intentional or unintentional. All unintended discrepancies were rated for their potential to cause patient harm. RESULTS: After screening 523 admissions, 151 patients were enrolled based on the inclusion criteria. Eighty-one patients (53.6%; 95% confidence interval, 45.7%-61.6%) had at least 1 unintended discrepancy. The most common error (46.4%) was omission of a regularly used medication. Most (61.4%) of the discrepancies were judged to have no potential to cause serious harm. However, 38.6% of the discrepancies had the potential to cause moderate to severe discomfort or clinical deterioration. CONCLUSIONS: Medication errors at the time of hospital admission are common, and some have the potential to cause harm. Better methods of ensuring an accurate medication history at the time of hospital admission are needed.

Aged↗
PubMed2005

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↗