Oxycodone, Hydromorphone, and the Risk of Suicide: A Retrospective Population-Based Case-Control Study.

INTRODUCTION: Opioids have been increasingly associated with suicide, but whether they are independent contributors is unclear. Oxycodone and hydromorphone are commonly prescribed high-potency opioids that can differentially affect mood. OBJECTIVE: The objective of this study was to explore whether oxycodone and hydromorphone are differentially associated with suicide. METHODS: We conducted a retrospective population-based case-control study in Ontario, Canada, from 1992 to 2014. Using coronial data, we defined case subjects as individuals who died by suicide involving an opioid overdose. Each of these was matched with up to four controls who died of accidental opioid overdose. We ascertained exposure to oxycodone, hydromorphone, and other opioids from postmortem toxicology testing. We used odds ratios and 95% confidence intervals to examine whether opioid-related suicide was disproportionately associated with oxycodone relative to hydromorphone. RESULTS: We identified 438 suicides and 1212 accidental deaths, each of which involved either oxycodone or hydromorphone but not both. The median age at death was 49 years and 51% were men. After adjusting for a history of self-harm, psychiatric illness, and exposure to other opioids, we found that oxycodone was more strongly associated with suicide than hydromorphone (adjusted odds ratio 1.59; 95% confidence interval 1.20-2.11). In a secondary analysis, we observed a trend of similar magnitude in which combined exposure to oxycodone and hydromorphone was more strongly associated with suicide than hydromorphone alone (adjusted odds ratio 1.68; 95% confidence interval 0.92-3.09). CONCLUSIONS: While preliminary, these findings support the possibility that some high-potency opioids might independently influence the risk of suicide in susceptible individuals.

Second-generation anti-depressants and risk of new-onset seizures in the elderly.

BACKGROUND: Anti-depressants are among the most widely-prescribed medications. It is unknown whether the risk of seizure during therapeutic use differs by drug. We ranked the seizure risk of popular anti-depressants. METHODS: We conducted a population-based case-control study between April 2002 and March 2015 in Ontario, Canada. Cases were Ontario residents aged ≥65 years hospitalized for a first-ever seizure within 60 d of filling a prescription for one of nine second-generation anti-depressants, each dispensed more than 1 million times (range: 1,196,810 [fluvoxamine] to 19,849,930 [citalopram]) during the study period. For each case, we identified up to four seizure-free controls receiving a similar anti-depressant, and matched on age, sex, date and a pre-defined seizure-specific disease risk index. RESULTS: We identified 5701 patients hospitalized with a first-ever seizure and matched them with 21,872 controls. Relative to bupropion, the risk of new-onset seizure during therapeutic use was highest for escitalopram (adjusted odds ratio [OR] 1.79; 95% confidence interval [CI] 1.42-2.25) and citalopram (OR 1.67; 95% CI 1.35-2.07), while no incremental risk was found for fluoxetine (OR 1.02; 95%CI 0.78-1.33) and duloxetine (OR 0.94; 95%CI 0.75-1.22). Other anti-depressants were associated with modest increase in seizure risk. CONCLUSIONS: The risk of seizure during therapeutic use among elderly patients varies among second-generation anti-depressants. Escitalopram and citalopram are associated with the highest risk. Prescribers should consider the seizure risk of individual anti-depressants and use discretion when selecting an anti-depressant, especially for patients with other risk factors for seizure. Frontline clinicians should be cognizant of this differential risk.

A population-based study of the risk of osteoporosis and fracture with dutasteride and finasteride.

BACKGROUND: Dutasteride is a potent inhibitor of 5-alpha reductase enzymes that reduces concentrations of dihydrotestosterone to a greater extent than finasteride. Whether this has adverse implications for bone health is unknown. We compared the risk of osteoporosis and fractures in older men treated with dutasteride or finasteride. METHODS: We conducted a population-based retrospective cohort study with high-dimensional propensity score matching of Ontario men aged 66 years or older who started treatment with dutasteride or finasteride between January 1, 2006 and December 31, 2012. The primary outcome was a diagnosis of osteoporosis within 2 years of treatment initiation. A secondary outcome was osteoporotic or fragility fractures. RESULTS: We studied 31,615 men treated with dutasteride and an equal number of men treated with finasteride. Dutasteride-treated patients had a lower incidence of osteoporosis than those receiving finasteride [2.2 versus 2.6 per 100 person years; hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.72 to 0.93]. This effect was no longer statistically significant following adjustment for specialty of prescribing physician (HR 0.90; 95% CI 0.78 to 1.02)]. There was no differential risk of fractures with dutasteride (HR 1.04; 95% 0.86 to 1.25). CONCLUSIONS: Despite differential effects on 5-alpha reductase, dutasteride is not associated with an increased risk of osteoporosis or fractures in older men relative to finasteride. These findings suggest that dutasteride does not adversely affect bone health.

Predictors of Critical Care and Mortality in Bronchiolitis after Emergency Department Discharge.

OBJECTIVES: To identify the epidemiologic predictors and stratify the risk of critical care unit (CCU) admission or death in bronchiolitis following emergency department discharge. This information has not yet been explored. STUDY DESIGN: A population-based cohort study using Ontario-wide demographic and healthcare databases linked at the individual level. We assessed all infants with bronchiolitis discharged home from all emergency departments in Ontario, Canada, 2003-2014. Targeted information included plausible demographic and clinical predictors of CCU admission/death within 14 days of emergency department discharge. Using multivariable logistic regression analyses, we identified independent predictors of this outcome and stratified the outcome risk by the type of multivariable predictor. RESULTS: Of 34 270 study infants, 102 (0.3%) were admitted to CCU or died after discharge. Predictors of CCU admission/death were: comorbidities (OR 5.33; 95% CI 2.82-10.10), younger age [months] (OR 1.47; 95%CI 1.33-1.61), low income (OR 1.53; 95% CI 1.01-2.34), younger gestational age [weeks] (OR 1.14; 95%CI 1.06-1.22), and emergent presentation (Canadian Triage and Acuity Scale 2) at the index visit (OR 1.55, 95% CI 1.03-2.33). The absolute event risk of CCU admission/death in infants with versus without comorbidities were 1.5% versus 0.26%, respectively (P < .001). The odds of these outcomes in infants with comorbidities plus ≥2 other predictors were 25 times higher than in infants without predictors (OR 25.1, 95% CI 11.4-55.3). CONCLUSIONS: Infants with comorbidities plus other predictors discharged from the emergency department with bronchiolitis are at considerable risk of subsequent CCU admission and death. These risk factors should augment current clinical and social considerations determining patient disposition.

Medication use and kidney cancer survival: A population-based study.

Several studies demonstrate that use of commonly prescribed medications is associated with improved survival in various malignancies. Methods of classifying medication use in many of these studies, however, do not account for intermittent or cumulative use. Moreover, there are limited data in kidney cancer. Therefore, we performed a population-based cohort study utilizing healthcare databases in Ontario, Canada. We identified patients aged ≥65 with an incident diagnosis of kidney cancer between 1997 and 2013 and examined use of nine putative anti-neoplastic medications using prescription claims. Cox proportional hazard models evaluated the association of medication exposure on cancer-specific and overall survival. We conducted three separate analyses: the effect of cumulative duration of exposure to the study medications on outcomes, the effect of current exposure (in a binary nature) and the effect of exposure at diagnosis. During the 16-year study period, we studied 9,124 patients. Increasing cumulative use of angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs) and selective serotonin reuptake inhibitors were associated with markedly improved cancer-specific survival; increasing use of NSAIDs was associated with markedly improved overall survival. These results were generally discordant with analyses evaluating the effect of current use and exposure at diagnosis. In conclusion, pharmacoepidemiology studies may be sensitive to the method of analysis; cumulative use analyses may be the most robust as it accounts for intermittent use and supports a dose-outcome relationship. Prospective studies are needed to confirm whether patients diagnosed with kidney cancer should be started on an angiotensin-converting enzyme inhibitor, NSAID or selective serotonin reuptake inhibitor to improve survival.

Concomitant pulmonologist and primary care for chronic obstructive pulmonary disease: a population study.

Background: Pulmonologists provide quality care, however, their number is not adequate to take care of all the chronic obstructive pulmonary disease (COPD) needs of the population and their services come with a cost. Their optimal role should be defined, ideally based on evidence, to ensure that their abilities are applied most efficiently where needed. Objective: To determine if concomitant pulmonologist and primary care physician care after COPD hospital or emergency department discharge was associated with better health outcomes than primary care services alone. Methods: A population cohort study was conducted in Ontario, Canada from 2004 to 2011. All individuals with a COPD hospital or emergency department discharge were included. Patients who visited both a pulmonologist and a primary care physician within 30 days of the index discharge were matched to patients who had visited a primary care physician alone using propensity scores. The composite outcome of death, COPD hospitalization or COPD emergency department visit was compared using proportional hazards regression. Results: In the propensity score matched sample, 39.7% of patients who received concomitant care and 38.9% who received primary care only died or visited the emergency department visit or hospital for COPD within 1 year (adjusted hazard ratio 1.08, 95% confidence interval 1.00-1.17). The former, however, were more likely to receive diagnostic testing and medications. Conclusion: Patients who received concomitant care after COPD emergency department or hospital discharge did not have better outcomes than those who received primary care alone, however, they did receive more testing and medical management.

Medication use and kidney cancer risk: A population-based study.

BACKGROUND: Exposure to commonly prescribed medications may be associated with cancer risk. However, there is limited data in kidney cancer. Furthermore, methods of classifying cumulative medication exposure in previous studies may be prone to bias. METHODS: We conducted a population-based case-control study of 10,377 incident kidney cancer cases aged ≥66 years matched with 35,939 controls on age, sex, history of hypertension, comorbidity score, and geographic location. Cumulative exposure to commonly prescribed medications hypothesised to modulate cancer risk was obtained using prescription claims data. We modelled exposure in four different fashions: (1) as continuous exposures using (a) fractional polynomials (which allow for a non-linear relationship between an exposure and outcome) or (b) assuming linear relationships; and 2) as dichotomous exposures denoting (a) ≥3 years versus <3 years exposure; or (b) "ever" versus "never" exposure. We used conditional logistic regression to estimate the association of medication exposure on incident kidney cancer. RESULTS: The directions of association were relatively consistent across analyses; however, the magnitudes were sensitive to the method of analysis. When utilising fractional polynomials, increasing cumulative exposure to acetylsalicylic acid, selective serotonin reuptake inhibitors, and proton-pump inhibitors was associated with significantly reduced risk of kidney cancer, while increasing exposure to antihypertensive drugs was associated with significantly increased risk. CONCLUSIONS: Our study provides impetus to further explore the effect of commonly prescribed medications on carcinogenesis to identify modifiable pharmacological interventions to reduce the risk of kidney cancer.

Lipophilic Statins and the Risk of Intracranial Hemorrhage Following Ischemic Stroke: A Population-Based Study.

BACKGROUND: Statins are commonly prescribed for the secondary prevention of ischemic stroke, but there is conflicting evidence as to whether they increase the risk of intracranial hemorrhage. Lipophilic statins cross the blood-brain barrier more freely than hydrophilic statins and may therefore increase the risk of intracranial hemorrhage. OBJECTIVE: To determine whether, in older patients following ischemic stroke, receipt of lipophilic statins was associated with differences in the risk of intracranial hemorrhage. METHODS: We conducted a population-based nested case-control study linking multiple healthcare databases between 1 April, 2001 and 31 March, 2015 in Ontario, Canada. Cases were Ontarians aged 66 years or older receiving a statin within 100 days preceding the development of intracranial hemorrhage within 1 year following ischemic stroke. Each case was matched with up to four controls who experienced ischemic stroke not complicated by intracranial hemorrhage but who also received a statin. We classified statins as lipophilic (atorvastatin, simvastatin, lovastatin, fluvastatin, and cerivastatin) or hydrophilic (pravastatin and rosuvastatin) based on their octanol/water partition coefficients. We calculated the odds ratio for the association between intracranial hemorrhage and receipt of lipophilic statins, with hydrophilic statins as the reference group. RESULTS: We identified 2766 individuals who experienced intracranial hemorrhage during statin therapy after ischemic stroke and 11,060 matched controls. Relative to hydrophilic statins, lipophilic statins were not associated with an increased risk of intracranial hemorrhage (adjusted odds ratio 1.07; 95% confidence interval 0.97-1.19). CONCLUSION: Among patients treated with a statin following ischemic stroke, the risk of intracranial hemorrhage is not influenced by statin lipophilicity.

Pregabalin and heart failure: A population-based study.

PURPOSE: The anticonvulsant pregabalin is increasingly prescribed for pain, seizures, and psychiatric disorders. Although evidence suggests pregabalin can cause edema and heart failure, its cardiac safety profile in clinical practice is unknown. We sought to examine the risk of heart failure among older patients receiving pregabalin compared to those receiving gabapentin. METHODS: We conducted a population-based cohort study of Ontarians aged 66 and older with a history of seizure who received pregabalin or gabapentin between April 2013 and March 2014. We used propensity scores to match patients commencing pregabalin to those commencing gabapentin. The primary outcome was an emergency department visit or hospitalization for heart failure within 90 days. RESULTS: We studied 9855 patients who initiated pregabalin and an equal number treated with gabapentin. In the primary analysis, we found no difference in the risk of heart failure with pregabalin compared to gabapentin (1.2% versus 1.3%, hazard ratio of 0.77; 95% CI 0.58-1.03). Secondary analyses stratified for baseline history of heart failure yielded similar findings. CONCLUSION: In a large cohort of older patients with a seizure disorder, pregabalin was not associated with an increased risk of heart failure relative to gabapentin.

Macrolides, Digoxin Toxicity and the Risk of Sudden Death: A Population-Based Study.

INTRODUCTION: Digoxin is commonly prescribed to elderly patients with heart failure and atrial fibrillation, and macrolide antibiotics markedly increase the risk of digoxin toxicity. OBJECTIVE: The aim was to determine whether, in older patients receiving digoxin, macrolide antibiotics are associated with sudden death. METHODS: We used a population-based, nested, case-control design from January 1, 1994 to December 31, 2012 in a cohort of Ontario residents aged 66 years or older prescribed digoxin. The primary outcome was the risk of sudden death within 14 days of exposure to one of three antibiotics (erythromycin, clarithromycin, or azithromycin), relative to cefuroxime. RESULTS: Among 39,072 Ontarians who died suddenly while receiving digoxin, 586 died within 14 days of receiving a study antibiotic. Relative to cefuroxime, we found no statistically significant increase in the risk of sudden death following treatment with erythromycin [adjusted odds ratio (aOR) 0.98; 95% confidence interval (CI) 0.65-1.48], clarithromycin (aOR 1.25; 95% CI 0.94-1.65), or azithromycin (aOR 1.07; 95% CI 0.75-1.53). CONCLUSION: This finding reinforces the cardiovascular safety of macrolide antibiotics in a high-risk population.

Association between statin use and ischemic stroke or major hemorrhage in patients taking dabigatran for atrial fibrillation.

BACKGROUND: Dabigatran etexilate is a prodrug whose absorption is opposed by intestinal P-glycoprotein and which is converted by carboxylesterase to its active form, dabigatran. Unlike other statins, simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase, and might either increase the risk of hemorrhage with dabigatran etexilate or decrease its effectiveness. METHODS: We conducted 2 population-based, nested case-control studies involving Ontario residents 66 years of age and older who started dabigatran etexilate between May 1, 2012, and Mar. 31, 2014. In the first study, cases were patients with ischemic stroke; in the second, cases were patients with major hemorrhage. Each case was matched with up to 4 controls by age and sex. All cases and controls received a single statin in the 60 days preceding the index date. We determined the association between each outcome and the use of simvastatin or lovastatin, relative to other statins. RESULTS: Among 45 991 patients taking dabigatran etexilate, we identified 397 cases with ischemic stroke and 1117 cases with major hemorrhage. After multivariable adjustment, use of simvastatin or lovastatin was not associated with an increased risk of stroke (adjusted odds ratio [OR] 1.33, 95% confidence interval [CI] 0.88 to 2.01). In contrast, use of simvastatin and lovastatin were associated with a higher risk of major hemorrhage (adjusted OR 1.46, 95% CI 1.17 to 1.82). INTERPRETATION: In patients receiving dabigatran etexilate, simvastatin and lovastatin were associated with a higher risk of major hemorrhage relative to other statins. Preferential use of the other statins should be considered in these patients.

Overdose Risk in Young Children of Women Prescribed Opioids.

BACKGROUND AND OBJECTIVE: Over the past 20 years, the prescribing of opioids has increased dramatically in North America, with parallel increases in opioid addiction, overdose, and associated deaths. We examined whether young children of women prescribed opioids were at increased risk of opioid overdose. METHODS: We conducted a population-based, nested case control study in Ontario, Canada, between 2002 and 2015. We identified children aged ≤10 years, whose mothers received publicly funded prescriptions for an opioid or a nonsteroidal antiinflammatory drug (comparator analgesic) in the preceding year. Cases were children who presented to hospital for or died of opioid overdose. Each case was matched with 4 controls with no opioid overdose. The primary outcome was the risk of opioid overdose. RESULTS: We identified 103 children who presented to the hospital with opioid overdose and matched them with 412 controls. Half of the children with opioid overdose were <2 years old. Compared with controls, children with an opioid overdose were far more likely to have a mother who received a prescription opioid (unadjusted odds ratio, 2.41; 95% confidence interval, 1.68-3.45) and who was prescribed antidepressants. The most commonly implicated overdose opioids were codeine (53.4%), oxycodone (32.0%), and methadone (15.5%). CONCLUSIONS: Young children of mothers prescribed opioids are at a markedly increased risk of overdose. Physicians, pharmacists, and parents should take measures to mitigate the risk of opioid-related harm to children, such as prescribing smaller quantities, emphasizing the importance of secure medication storage, and the prompt disposal of unused opioids.

The Cardiovascular Safety of Dutasteride.

PURPOSE: Randomized controlled trials suggest an increased risk of heart failure with dutasteride, which inhibits both the type 1 and type 2 isoforms of 5α-reductase. In contrast, no such association has been suggested for finasteride, which selectively inhibits the type 2 isoform. We investigated the risk of cardiovascular events among patients receiving dutasteride relative to finasteride. MATERIALS AND METHODS: We performed a population based cohort study of Ontario men 66 years old or older who commenced treatment with dutasteride or finasteride between October 1, 2005 and March 31, 2015. For each individual treated with dutasteride, we identified 1 treated with finasteride, matching on a propensity score and calendar quarter of treatment initiation to account for temporal changes in prescribing. The primary outcome was hospitalization for heart failure. Secondary analyses were done to examine acute myocardial infarction and stroke. Cox proportional hazards regression was used to adjust for differences between groups. RESULTS: We studied 36,311 men who commenced dutasteride and 36,311 treated with finasteride. In the primary analysis, we found no difference in the risk of heart failure among patients receiving dutasteride relative to those receiving finasteride (adjusted HR 0.98, 95% CI 0.88-1.08). Similarly, we found no difference in the risk of acute myocardial infarction (HR 0.94, 95% CI 0.82-1.08) or stroke (HR 1.03, 95% CI 0.88-1.20). CONCLUSIONS: In this population based cohort study of more than 72,000 older men, dutasteride was not associated with an increased risk of cardiovascular events relative to finasteride.

Cost evaluation of out-of-country care for patients with eating disorders in Ontario: a population-based study.

BACKGROUND: Eating disorders, specifically anorexia nervosa, bulimia nervosa and eating disorder not otherwise specified, represent a substantial burden to the health care system. Our goal was to estimate the economic burden of patients who received specialized inpatient care for an eating disorder out of country. METHOD: We conducted a cost-of-illness study evaluating health care costs among patients in Ontario who received specialized inpatient care for an eating disorder out of country from 2003 to 2011, from the public third-party payer perspective. Using linked administrative databases, we estimated net costs of eating disorders for 2 patient groups: those who received specialized inpatient care both out of country and in province (n = 160), and those who received specialized inpatient care out of country only (n = 126). RESULTS: Patients approved for specialized out-of-country inpatient care were mostly girls and young women from high-income, urban neighbourhoods. Total net costs varied annually and were higher for patients treated both out of country and in province (about $11 million before 2007, $6.5 million after) than for those treated out of country alone (about $5 million and $2 million, respectively). The main cost drivers were out-of-country care and physician services. INTERPRETATION: Costs associated with eating disorder care represent a substantial economic burden to the Ontario health care system. Given the high costs of out-of-country care, there may be opportunity to redirect these funds to increase capacity and expertise for eating disorder treatment within Ontario.

Vasectomy and risk of prostate cancer: population based matched cohort study.

OBJECTIVE:  To determine the association between vasectomy and prostate cancer, adjusting for measures of health seeking behaviour. DESIGN:  Population based matched cohort study. SETTING:  Multiple validated healthcare databases in Ontario, Canada, 1994-2012. PARTICIPANTS:  326 607 men aged 20 to 65 who had undergone vasectomy were identified through physician billing codes and matched 1:1 on age (within two years), year of cohort entry, comorbidity score, and geographical region to men who did not undergo a vasectomy. MAIN OUTCOMES MEASURES:  The primary outcome was incident prostate cancer. Secondary outcomes were prostate cancer related grade, stage, and mortality. RESULTS:  3462 incident cases of prostate cancer were identified after a median follow-up of 10.9 years: 1843 (53.2%) in the vasectomy group and 1619 (46.8%) in the non-vasectomy group. In unadjusted analysis, vasectomy was associated with a slightly increased risk of incident prostate cancer (hazard ratio 1.13, 95% confidence interval 1.05 to 1.20). After adjustment for measures of health seeking behaviour, however, no association remained (adjusted hazard ratio 1.02, 95% confidence interval 0.95 to 1.09). Moreover, no association was found between vasectomy and high grade prostate cancer (adjusted odds ratio 1.05, 95% confidence interval 0.67 to 1.66), advanced stage prostate cancer (adjusted odds ratio 1.04, 0.81 to 1.34), or mortality (adjusted hazard ratio 1.06, 0.60 to 1.85). CONCLUSION:  The findings do not support an independent association between vasectomy and prostate cancer.

Medication use and survival in diabetic patients with kidney cancer: A population-based cohort study.

Survival rates in kidney cancer have improved little over time, and diabetes may be an independent risk factor for poor survival in kidney cancer. We sought to determine whether medications with putative anti-neoplastic properties (statins, metformin and non-steroidal anti-inflammatory drugs (NSAIDs)) are associated with survival in diabetics with kidney cancer. We conducted a population-based cohort study utilizing linked healthcare databases in Ontario, Canada. Patients were aged 66 or older with newly diagnosed diabetes and a subsequent diagnosis of incident kidney cancer. Receipt of metformin, statins or NSAIDs was defined using prescription claims. The primary outcome was all-cause mortality and the secondary outcome was cancer-specific mortality. We used multivariable Cox proportional hazard regression, with medication use modeled with time-varying and cumulative exposure analyses to account for intermittent use. During the 14-year study period, we studied 613 patients. Current statin use was associated with a markedly reduced risk of death from any cause (adjusted hazard ratio 0.74; 95% CI 0.59-0.91) and death due to kidney cancer (adjusted hazard ratio 0.71; 95% CI 0.51-0.97). However, survival was not associated with current use of metformin or NSAIDs, or cumulative exposure to any of the medications studied. Among diabetic patients with kidney cancer, survival outcomes are associated with active statin use, rather than total cumulative use. These findings support the use of randomized trials to confirm whether diabetics with kidney cancer should be started on a statin at the time of cancer diagnosis to improve survival outcomes.

Repetition of intentional drug overdose: a population-based study.

CONTEXT: Intentional overdose is a leading method of self-harm and suicide, and repeat attempts strongly predict eventual death by suicide. OBJECTIVES: To determine the risk of recurrence after a first intentional overdose. Secondary objectives included characterization of the temporal course and potential predictors of repeat overdose, a strong risk factor for death from suicide. DESIGN: Population-based cohort study. SETTING: Ontario, Canada, from 1 April 2002 to 31 March 2013. PARTICIPANTS: All Ontario residents presenting to an emergency department after a first intentional overdose. MAIN OUTCOME MEASURES: The incidence and timing of recurrent overdose. RESULTS: We followed 81,675 patients discharged from hospital after a first intentional overdose. Overall, 13,903 (17.0%) returned with a repeat overdose after a median interval of 288 (inter-quartile range: 62 to 834) days. Of these, 4493 (5.5%) had multiple repeat episodes. Factors associated with repeat self-poisoning included psychiatric care in the preceding year (adjusted hazard ratio [aHR] 1.55; 95% confidence interval [CI] 1.50 to 1.61), alcohol dependence (aHR 1.41; 95% CI 1.35 to 1.46) and documented depression (aHR 1.39; 95% CI 1.34 to 1.44). Female sex, rural residence, lower socioeconomic status, ingestion of psychoactive drugs and younger age were also weakly associated with repeat overdose. DISCUSSION: Hospital presentation for repetition of intentional overdose is common, with recurrent episodes often far removed from the first. While several factors predict overdose repetition, none is particularly strong. CONCLUSION: Secondary prevention initiatives should be implemented for all individuals who present to the emergency department and survive intentional overdose.

Antiepileptic use for epilepsy and nonepilepsy disorders: A population-based study (1998-2013).

OBJECTIVE: To examine the trends in antiepileptic drug (AED) use among individuals living in Manitoba with and without a history of epilepsy. METHODS: Using data obtained from administrative health databases in Manitoba, we assessed the quarterly prevalence of AED use between 1998 and 2013 among individuals with and without a history of epilepsy using cross-sectional time series analysis. RESULTS: Over the study period, the number of individuals prescribed AEDs increased more than 3-fold, from 8,883 to 27,246. The prevalence of AED use among patients with epilepsy increased by 3%, from 789.6 per 1,000 in 1998/1999 to 813.9 per 1,000 in 2012/2013 (p < 0.001 after 2006). In contrast, we observed a 210% increase in AED use among patients without epilepsy from 6.8 to 21.1 per 1,000 over the same period (p < 0.001). We observed a 55-fold rise in gabapentin use among patients without a seizure disorder (from 0.2 to 11.1 per 1,000; p < 0.001), while gabapentin use among those with epilepsy increased only 2-fold, from 21.6 to 41.3 per 1,000 (p < 0.001). CONCLUSIONS: There has been a marked increase in the prevalence of AED users over the last 15 years, with a large shift towards the use of newer antiepileptic agents (primarily gabapentin) among those without epilepsy. Further research on the effect of these trends on health and economic outcomes will be of interest for clinicians and policymakers.