Alexander Kopp

β blockers for elective surgery in elderly patients: population based, retrospective cohort study

Abstract Objective To test whether atenolol (a long acting β blocker) and metoprolol (a short acting β blocker) are associated with equivalent reductions in risk for elderly patients undergoing elective surgery. Design Population based, retrospective cohort analysis. Setting Acute care hospitals in Ontario, Canada, over one decade. Participants Consecutive patients older than 65 who were admitted for elective surgery, without symptomatic coronary disease. Main outcome measure Death or myocardial infarction. Results 37 151 patients were receiving atenolol or metoprolol before surgery, of which the most common operations were orthopaedic or abdominal procedures. As expected, the two groups were similar in demographic characteristics, medical therapy, and type of surgery. 1038 patients experienced a myocardial infarction or died, a rate that was significantly lower for patients receiving atenolol than for those receiving metoprolol(2.5% v 3.2%, P < 0.001). The decreased risk with atenolol persisted after adjustment for measured demographic, medical, and surgical factors; extended to comparisons of other long acting and short acting βblockers; was accentuated in analyses that focused on patients with the clearest evidence β blocker treatment; and reflected the immediate postoperative interval. Conclusions Patients receiving metoprolol do not have as low a perioperative cardiac risk as patients receiving atenolol, in accord with possible acute withdrawal after missed doses.

Proton Pump Inhibitors and Hospitalization for Clostridium Difficile—Associated Disease: A Population-Based Study

BACKGROUND Previous studies have examined the association between proton pump inhibitor (PPI) use and the risk of Clostridium difficile-associated disease (CDAD), with conflicting results. Whether outpatient PPI use influences the risk of hospital admission for CDAD among older patients who have recently been treated with antibiotics is unknown. METHODS We conducted a population-based, nested case-control study of linked health care databases in Ontario, Canada, from 1 April 2002 through 31 March 2005. We identified patients aged > or = 66 years who were hospitalized for CDAD within 60 days of receiving outpatient antibiotic therapy. Each case patient with CDAD was matched with 10 control subjects on the basis of age, sex, and details of antibiotic use (antibiotic class, timing, and number of antibiotics used). PPI use by case patients and control subjects was categorized as current (within 90 days), recent (91-180 days), or remote (181-365 days). We used conditional logistic regression to estimate the odds ratio for the association between outpatient PPI use and risk of hospitalization for CDAD. RESULTS We identified 1389 case patients and 12,303 matched control subjects. Case patients were no more likely than control subjects to have received a PPI in the preceding 90 days (adjusted odds ratio, 0.9; 95% confidence interval, 0.8-1.1). Similarly, we found no association between hospitalization for CDAD and more remote use of PPIs. CONCLUSIONS Among community-dwelling older patients, PPI use is not a risk factor for hospitalization with CDAD.

Living near major roads and the incidence of dementia, Parkinson's disease, and multiple sclerosis: a population-based cohort study

BACKGROUND Emerging evidence suggests that living near major roads might adversely affect cognition. However, little is known about its relationship with the incidence of dementia, Parkinsons disease, and multiple sclerosis. We aimed to investigate the association between residential proximity to major roadways and the incidence of these three neurological diseases in Ontario, Canada. METHODS In this population-based cohort study, we assembled two population-based cohorts including all adults aged 20-50 years (about 4·4 million; multiple sclerosis cohort) and all adults aged 55-85 years (about 2·2 million; dementia or Parkinsons disease cohort) who resided in Ontario, Canada on April 1, 2001. Eligible patients were free of these neurological diseases, Ontario residents for 5 years or longer, and Canadian-born. We ascertained the individuals proximity to major roadways based on their residential postal-code address in 1996, 5 years before cohort inception. Incident diagnoses of dementia, Parkinsons disease, and multiple sclerosis were ascertained from provincial health administrative databases with validated algorithms. We assessed the associations between traffic proximity and incident dementia, Parkinsons disease, and multiple sclerosis using Cox proportional hazards models, adjusting for individual and contextual factors such as diabetes, brain injury, and neighbourhood income. We did various sensitivity analyses, such as adjusting for access to neurologists and exposure to selected air pollutants, and restricting to never movers and urban dwellers. FINDINGS Between 2001, and 2012, we identified 243 611 incident cases of dementia, 31 577 cases of Parkinsons disease, and 9247 cases of multiple sclerosis. The adjusted hazard ratio (HR) of incident dementia was 1·07 for people living less than 50 m from a major traffic road (95% CI 1·06-1·08), 1·04 (1·02-1·05) for 50-100 m, 1·02 (1·01-1·03) for 101-200 m, and 1·00 (0·99-1·01) for 201-300 m versus further than 300 m (p for trend=0·0349). The associations were robust to sensitivity analyses and seemed stronger among urban residents, especially those who lived in major cities (HR 1·12, 95% CI 1·10-1·14 for people living <50 m from a major traffic road), and who never moved (1·12, 1·10-1·14 for people living <50 m from a major traffic road). No association was found with Parkinsons disease or multiple sclerosis. INTERPRETATION In this large population-based cohort, living close to heavy traffic was associated with a higher incidence of dementia, but not with Parkinsons disease or multiple sclerosis. FUNDING Health Canada (MOA-4500314182).

Drug‐Induced Lithium Toxicity in the Elderly: A Population‐Based Study

Objectives: To study the association between hospital admission for lithium toxicity and the use of diuretics, angiotensin‐converting enzyme (ACE) inhibitors, and nonsteroidal antiinflammatory drugs (NSAIDs) in the elderly.

Spatial association between ambient fine particulate matter and incident hypertension

Background— Laboratory studies suggest that exposure to fine particulate matter (⩽2.5 &mgr;m in diameter) (PM2.5) can trigger a combination of pathophysiological responses that may induce the development of hypertension. However, epidemiological evidence relating PM2.5 and hypertension is sparse. We thus conducted a population-based cohort study to determine whether exposure to ambient PM2.5 is associated with incident hypertension. Methods and Results— We assembled a cohort of 35 303 nonhypertensive adults from Ontario, Canada, who responded to 1 of 4 population-based health surveys between 1996 and 2005 and were followed up until December 31, 2010. Incident diagnoses of hypertension were ascertained from the Ontario Hypertension Database, a validated registry of persons diagnosed with hypertension in Ontario (sensitivity=72%, specificity=95%). Estimates of long-term exposure to PM2.5 at participants’ postal-code residences were derived from satellite observations. We used Cox proportional hazards models, adjusting for various individual and contextual risk factors including body mass index, smoking, physical activity, and neighbourhood-level unemployment rates. We conducted various sensitivity analyses to assess the robustness of the effect estimate, such as investigating several time windows of exposure and controlling for potential changes in the risk of hypertension over time. Between 1996 and 2010, we identified 8649 incident cases of hypertension and 2296 deaths. For every 10-µg/m3 increase of PM2.5, the adjusted hazard ratio of incident hypertension was 1.13 (95% confidence interval, 1.05–1.22). Estimated associations were comparable among all sensitivity analyses. Conclusions— This study supports an association between PM2.5 and incident hypertension.

Antidepressants, warfarin, and the risk of hemorrhage

Background: Case reports suggest that some selective serotonin reuptake inhibitors can interact with warfarin to increase the likelihood of bleeding. We speculated that, among patients receiving warfarin, initiation of selective serotonin reuptake inhibitor treatment would be associated with an increased risk of hospitalization for upper gastrointestinal tract bleeding (UGIB). Methods: We conducted a population-based, nested, case-control study involving Ontario residents 66 years or older continuously treated with warfarin for at least 1 year. Cases admitted with UGIB were compared with matched controls (1:10) to explore the odds ratio for initiation of various antidepressants within 42, 90, and 180 days before the index admission. Results: From January 1994 to December 2002, we identified 98,784 elderly patients continuously receiving warfarin for at least 1 year; of whom 1538 (0.6%) were admitted to hospital for UGIB. The adjusted odds ratio for fluoxetine/fluvoxamine exposure in 90 days before UGIB hospitalization is 1.2 (95% confidence interval, 0.8-1.7), and the adjusted odds ratio for other selective serotonin reuptake inhibitors in the same period was 1.1 (95% confidence interval, 0.9-1.4). The odds ratios for exposure to antidepressants in 180 days before UGIB hospitalization were similar. Conclusion: The initiation of selective serotonin reuptake inhibitor treatment in patients receiving warfarin was not associated with a significant increase in the risk of hospitalization for UGIB.

Hemorrhage During Warfarin Therapy Associated With Cotrimoxazole and Other Urinary Tract Anti-infective Agents A Population-Based Study

BACKGROUND Some antibiotic agents, including cotrimoxazole, inhibit the metabolism of warfarin sodium and possibly increase the risk of hemorrhage. We examined the risk of upper gastrointestinal (UGI) tract hemorrhage in older patients receiving warfarin in combination with antibiotics commonly used to treat urinary tract infection, with a focus on cotrimoxazole. METHODS This population-based, nested case-control study using health care databases in Ontario, Canada, between April 1, 1997, and March 31, 2007, identified residents 66 years or older who were continuously treated with warfarin. Cases were hospitalized with UGI tract hemorrhage. For each case, we selected up to 10 age- and sex-matched control subjects. We calculated adjusted odds ratios (aORs) for exposure to cotrimoxazole, amoxicillin trihydrate, ampicillin trihydrate, ciprofloxacin hydrochloride, nitrofurantoin, and norfloxacin within 14 days before the UGI tract hemorrhage. RESULTS We identified 134 637 patients receiving warfarin, of whom 2151 cases were hospitalized for UGI tract hemorrhage. Cases were almost 4 times more likely than controls to have recently received cotrimoxazole (aOR, 3.84; 95% confidence interval [CI], 2.33-6.33). Treatment with ciprofloxacin was also associated with increased risk (aOR, 1.94; 95% CI, 1.28-2.95), but no significant association was observed with amoxicillin or ampicillin (1.37; 0.92-2.05), nitrofurantoin (1.40; 0.71-2.75), or norfloxacin (0.38; 0.12-1.26). Compared with amoxicillin or ampicillin, cotrimoxazole prescription was associated with an almost 3-fold risk (ratio of ORs, 2.80; 95% CI, 1.48-5.32). CONCLUSIONS Among older patients receiving warfarin, cotrimoxazole is associated with a significantly higher risk of UGI tract hemorrhage than other commonly used antibiotics. Whenever possible, clinicians should prescribe alternative antibiotics in patients receiving warfarin.

Ambient Fine Particulate Matter and Mortality among Survivors of Myocardial Infarction: Population-Based Cohort Study.

Background: Survivors of acute myocardial infarction (AMI) are at increased risk of dying within several hours to days following exposure to elevated levels of ambient air pollution. Little is known, however, about the influence of long-term (months to years) air pollution exposure on survival after AMI. Objective: We conducted a population-based cohort study to determine the impact of long-term exposure to fine particulate matter ≤ 2.5 μm in diameter (PM2.5) on post-AMI survival. Methods: We assembled a cohort of 8,873 AMI patients who were admitted to 1 of 86 hospital corporations across Ontario, Canada in 1999–2001. Mortality follow-up for this cohort extended through 2011. Cumulative time-weighted exposures to PM2.5 were derived from satellite observations based on participants’ annual residences during follow-up. We used standard and multilevel spatial random-effects Cox proportional hazards models and adjusted for potential confounders. Results: Between 1999 and 2011, we identified 4,016 nonaccidental deaths, of which 2,147 were from any cardiovascular disease, 1,650 from ischemic heart disease, and 675 from AMI. For each 10-μg/m3 increase in PM2.5, the adjusted hazard ratio (HR10) of nonaccidental mortality was 1.22 [95% confidence interval (CI): 1.03, 1.45]. The association with PM2.5 was robust to sensitivity analyses and appeared stronger for cardiovascular-related mortality: ischemic heart (HR10 = 1.43; 95% CI: 1.12, 1.83) and AMI (HR10 = 1.64; 95% CI: 1.13, 2.40). We estimated that 12.4% of nonaccidental deaths (or 497 deaths) could have been averted if the lowest measured concentration in an urban area (4 μg/m3) had been achieved at all locations over the course of the study. Conclusions: Long-term air pollution exposure adversely affects the survival of AMI patients. Citation: Chen H, Burnett RT, Copes R, Kwong JC, Villeneuve PJ, Goldberg MS, Brook RD, van Donkelaar A, Jerrett M, Martin RV, Brook JR, Kopp A, Tu JV. 2016. Ambient fine particulate matter and mortality among survivors of myocardial infarction: population-based cohort study. Environ Health Perspect 124:1421–1428; http://dx.doi.org/10.1289/EHP185

Antipsychotic use in older adults with Parkinson's disease

The choice of agents to treat psychotic symptoms in Parkinsons disease is important given the potential for antipsychotics to worsen Parkinsonism. The purpose of this study was to estimate the incidence of psychotic symptoms requiring treatment in individuals with Parkinsons disease after starting dopaminergic medications, and to describe the agents being selected as initial antipsychotic therapy. Using the administrative health care databases of Ontario, Canada, individuals 66 years of age or older with Parkinsons disease who were newly treated with dopaminergic agents were identified. Subsequent prescriptions for antipsychotic medications were then identified. A total of 10,347 older adults were newly started on dopaminergic agents between 1998 and 2003. The Kaplan–Meier estimate for the cumulative probability of requiring an antipsychotic at 7 years was 35%; 499 individuals (4.8%; 5.2/100 person–years) were prescribed an antipsychotic within 1 year of starting dopaminergic therapy. The proportion of initial antipsychotic prescriptions for typical antipsychotics decreased from 56% (42 of 75) in 1998 to 9% (8 of 88) in 2002. Antipsychotic use is common in individuals with Parkinsonism newly treated with dopaminergic medication. Typical antipsychotics are still commonly being chosen as first‐line agents for older patients, indicating a need for interventions to improve practice.

Inequitable distribution of implantable cardioverter defibrillators in Ontario

OBJECTIVES Implantable cardioverter defibrillator (ICD) therapy reduces the risk of sudden death in patients with ischemic cardiomyopathy, but their novelty and cost may represent barriers to utilization. The objective of this study was to examine the influence of age, gender, place of residence, and socioeconomic status on rates of ICD implantation for the primary prevention of death. METHODS We conducted a population-based retrospective cohort study involving the entire province of Ontario, Canada. Patients were eligible if they had survived following hospitalization for heart failure from 1 January 1993, to 31 March 2004, and previously sustained an acute coronary syndrome within 5 years. Patients with an existing ICD or a documented history of cardiac arrest were excluded, as were patients who died in the hospital. Primary outcome was ICD implantation. RESULTS We identified 48,426 patients hospitalized for heart failure who survived to hospital discharge. Of these, 440 received an ICD, with a gradual 30-fold increase in implantation rates over the study period (.12-3.9 percent). ICD recipients were more likely to be men (odds ratio [OR]=4.14; 95 percent confidence interval [CI], 3.24-5.30), younger than 75 years of age (OR=3.19; 95 percent CI, 2.57-3.96), reside in a metropolitan area (OR=1.42; 95 percent CI, 1.04-1.9), and live in a higher socioeconomic neighborhood (OR=1.32; 95 percent CI, 1.08-1.61). CONCLUSIONS Among patients with heart failure and a previous myocardial infarction, ICD use is increasing in Ontario. However, the application of this technology is characterized by major sociodemographic inequities. The causes and consequences of the pronounced age and gender discrepancies, in particular, warrant further investigation.