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Background Utilization of psychotropic medications among the elderly has garnered attention due to concerns about safety and degree of efficacy, but may be used differently across regions. Methods We conducted a cross-sectional study of all antipsychotic, benzodiazepine, and trazodone prescriptions dispensed to seniors (≥ 65 years) leveraging IQVIA (Durham, NC) GPM data in 2013. We report the units dispensed (per 100 seniors) by province. Results Nationally, on average, 26,210 units of antipsychotics, 24,257 of benzodiazepines, and 7,519 of trazodone were dispensed in 2013 for every 100 seniors; reports varied across Canada. The rate of antipsychotic and benzodiazepine prescribing was highest in New Brunswick (AP: 35,375 units per 100, BZD: 43,989 units per 100), and lowest in Newfoundland & Labrador for antipsychotics (20,974 per 100) and Saskatchewan for benzodiazepines (12,692 per 100). Trazodone unit dispensation rates were highest in Nova Scotia (9,164 per 100) and lowest in Newfoundland & Labrador (2,968 per 100). Conclusions There is considerable geographic variation in the prescribing patterns of antipsychotics, benzodiazepine, and trazodone. This study serves as the first step in understanding these differences, while future work is needed to develop regionspecific strategies to optimize the prescribing of psychotropic medications to older Canadian adults. [ABSTRACT FROM AUTHOR]

Background: Prescription opioid use is highly associated with risk of opioid-related death, with 1 of every 550 chronic opioid users dying within approximately 2.5 years of their first opioid prescription. Although gabapentin is widely perceived as safe, drug-induced respiratory depression has been described when gabapentin is used alone or in combination with other medications. Because gabapentin and opioids are both commonly prescribed for pain, the likelihood of co-prescription is high. However, no published studies have examined whether concomitant gabapentin therapy is associated with an increased risk of accidental opioid-related death in patients receiving opioids. The objective of this study was to investigate whether co-prescription of opioids and gabapentin is associated with an increased risk of accidental opioid-related mortality.Methods and Findings: We conducted a population-based nested case-control study among opioid users who were residents of Ontario, Canada, between August 1, 1997, and December 31, 2013, using administrative databases. Cases, defined as opioid users who died of an opioid-related cause, were matched with up to 4 controls who also used opioids on age, sex, year of index date, history of chronic kidney disease, and a disease risk index. After matching, we included 1,256 cases and 4,619 controls. The primary exposure was concomitant gabapentin use in the 120 days preceding the index date. A secondary analysis characterized gabapentin dose as low (<900 mg daily), moderate (900 to 1,799 mg daily), or high (≥1,800 mg daily). A sensitivity analysis examined the effect of concomitant nonsteroidal anti-inflammatory drug (NSAID) use in the preceding 120 days. Overall, 12.3% of cases (155 of 1,256) and 6.8% of controls (313 of 4,619) were prescribed gabapentin in the prior 120 days. After multivariable adjustment, co-prescription of opioids and gabapentin was associated with a significantly increased odds of opioid-related death (odds ratio [OR] 1.99, 95% CI 1.61 to 2.47, p < 0.001; adjusted OR [aOR] 1.49, 95% CI 1.18 to 1.88, p < 0.001) compared to opioid prescription alone. In the dose-response analysis, moderate-dose (OR 2.05, 95% CI 1.46 to 2.87, p < 0.001; aOR 1.56, 95% CI 1.06 to 2.28, p = 0.024) and high-dose (OR 2.20, 95% CI 1.58 to 3.08, p < 0.001; aOR 1.58, 95% CI 1.09 to 2.27, p = 0.015) gabapentin use was associated with a nearly 60% increase in the odds of opioid-related death relative to no concomitant gabapentin use. As expected, we found no significant association between co-prescription of opioids and NSAIDs and opioid-related death (OR 1.11, 95% CI 0.98 to 1.27, p = 0.113; aOR 1.14, 95% CI 0.98 to 1.32, p = 0.083). In an exploratory analysis of patients at risk of combined opioid and gabapentin use, we found that 46.0% (45,173 of 98,288) of gabapentin users in calendar year 2013 received at least 1 concomitant prescription for an opioid. This study was limited to individuals eligible for public drug coverage in Ontario, we were only able to identify prescriptions reimbursed by the government and dispensed from retail pharmacies, and information on indication for gabapentin use was not available. Furthermore, as with all observational studies, confounding due to unmeasured variables is a potential source of bias.Conclusions: In this study we found that among patients receiving prescription opioids, concomitant treatment with gabapentin was associated with a substantial increase in the risk of opioid-related death. Clinicians should consider carefully whether to continue prescribing this combination of products and, when the combination is deemed necessary, should closely monitor their patients and adjust opioid dose accordingly. Future research should investigate whether a similar interaction exists between pregabalin and opioids. [ABSTRACT FROM AUTHOR]

Background: Direct oral anticoagulants (DOACs) have expanded the armamentarium for antithrombotic therapy. Although DOAC-related major bleeding was associated with favorable outcomes compared with warfarin in clinical trials, warfarin effects were reversed in < 40% of cases, raising concerns about the generalizability of this finding.Methods: Consecutive patients ≥ 66 years presented to five tertiary care hospitals across three cities in Ontario, Canada from October 2010 to March 2015 with diagnoses that included hemorrhage. Charts were screened for association with DOAC or warfarin use; eligible cases were abstracted and linked to administrative databases.Results: Among 19,061 records screened, 2,002 (460 receiving DOAC, 1,542 receiving warfarin) were eligible. Reversal agents (72.9% vitamin K, 40.7% prothrombin complex concentrates) were frequently used in warfarin bleeding events. Red blood cell transfusions occurred more often in DOAC bleeding events than in warfarin events (52.0% vs 39.5%; adjusted relative risk [aRR], 1.32; 95% CI, 1.19-2.47). However, units of blood products transfused were not different between the two groups. Thirty-four DOAC cases (7.4%) received activated prothrombin complex concentrates or recombinant factor VIIa. In-hospital mortality was lower following DOAC bleeding events (9.8% vs 15.2%; aRR, 0.66; 95% CI, 0.49-0.89), although differences in 30-day mortality did not reach statistical significance (12.6% vs 16.3%; aRR, 0.79; 95% CI, 0.61-1.03).Conclusions: In this unselected cohort of patients with oral anticoagulant-related hemorrhage with high rates of warfarin reversal, in-hospital mortality was lower among DOAC-associated bleeding events. These findings support the safety of DOACs in routine care and present useful baseline measures for evaluations of DOAC-specific reversal agents. [ABSTRACT FROM AUTHOR]

Background: A randomized controlled trial of adults with empyema recently demonstrated decreased length of stay in hospital in patients treated with intrapleurally administered dornase alfa and fibrinolytics compared to fibrinolytics alone. Whether this treatment strategy is safe and effective in children remains unknown.Methods/design: This study protocol is for a superiority, placebo-controlled, parallel-design, multicenter randomized controlled trial. The participants are previously well children admitted to a children's hospital with a diagnosis of empyema requiring chest tube insertion and fibrinolytics administered intrapleurally. Children will be randomized after the treating physician has decided that pleural drainage is required but prior to chest tube insertion. After chest tube insertion, participants in the treatment group will receive intrapleurally administered tissue plasminogen activator (tPA) 4 mg followed by dornase alfa 5 mg. Participants in the placebo group will receive tPA 4 mg followed by normal saline. Study treatments will be administered once daily for 3 days. All participants, parents or caregivers, clinicians, and research personnel will remain blinded. The primary outcome is length of stay from chest tube insertion to discharge from hospital. Secondary outcomes include time to meeting discharge criteria, chest tube duration, fever duration, need for additional procedures, adverse events, hospital readmission, cost of hospitalization, and mortality.Discussion: This multicenter randomized controlled trial will assess the safety, effectiveness, and cost-effectiveness of combined treatment with dornase alfa and fibrinolytics compared to fibrinolytics alone for the treatment of empyema in children.Trial Registration: ClinicalTrials.gov: NCT01717742 . Registered on 8 October 2012. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Provincial drug-program policies for the reimbursement of testosterone replacement therapy (TRT) vary across Canada, which may result in marked regional variability in use.Methods: We conducted a population-based cross-sectional analysis of provincially funded TRT spending and utilization in eight provinces across Canada in 2012. We reported the annual cost per user, total cost, and rate of use of TRT overall and by formulation.Results: We identified 23,544 provincially-funded recipients of TRT in 2012 in the eight provinces studied. Average annual cost per person varied by 3-fold, ranging from $173 (Prince Edward Island) to $485 (Ontario). Ontario also had the highest rate of use (1,105 users per 100,000 eligible) and the most liberal listing. Provinces with more restricted access (Alberta, British Columbia, and PEI) had lower annual costs per user ($293, $206, $173, respectively).Conclusions: Differing reimbursement policies for TRT products across Canada are likely contributing to variation in the rate of use and cost per recipient. [ABSTRACT FROM AUTHOR]

Background: Smoking remains a serious public health concern. Pharmacotherapy for smoking cessation, including bupropion and varenicline, are proven means to increase quit rates. Post-marketing reports describing suicidal behaviours have raised concerns about the safety of varenicline. However, whether varenicline imparts a higher risk of suicide relative to bupropion remains uncertain. Methods: A population-based nested case-control study in Ontario, Canada, from April 1, 2011 to March 31, 2015 was conducted. Subjects were residents of Ontario aged 18 years and older with publicly funded drug coverage receiving either bupropion or varenicline for smoking cessation. We defined cases were those with a hospitalization or emergency department visit for suicide or non-fatal self-harm within 90 days of treatment. For each case, we identified up to fifty controls from the same cohort matched on age, sex, history of self-harm, use of selected psychotropic medications, alcohol abuse and prior admission to a mental health unit. Adjusted odds ratio were used to compare the risk of suicide/self-harm of varenicline to bupropion. Results: We identified 331 cases and 5,346 matched-controls. Following adjustment for potential confounders, we found that varenicline was not associated with an increased risk of suicide/self-harm relative to bupropion (adjusted odds ratio 1.15; 95% confidence interval 0.71 to 1.87). Interpretation: Treatment with varenicline does not appear to significantly increase the risk of suicide or self-harm relative to bupropion. [ABSTRACT FROM AUTHOR]

Background: Patients are vulnerable to medication-related errors during transitions in care. Patients discharged from acute care hospitals may be at an elevated risk for the unintentional continuation of medications prescribed to prevent or treat complications that are associated with acute illness but are no longer indicated. We sought to evaluate rates of (primary objective) and risk factors for (secondary objective) potentially unintentional medication continuation following hospitalization.Methods: A population-based cohort study of more than one million patients 66 years of age or older who were hospitalized in Ontario, Canada, between 2003 and 2011 and followed for 1 year (2004 to 2012). We created distinct cohorts by identifying seniors not previously receiving four classes of medications typically used to treat or prevent complications of acute illness: (1) antipsychotic medications, (2) gastric acid suppressants (histamine-2 blockers and proton pump inhibitors), (3) benzodiazepines, and (4) inhaled bronchodilators and steroids. After excluding documented indications, we followed patients to ascertain whether these medications were continued after hospital discharge, and assessed risk factors for their continuation using generalized estimating equations. The primary outcome was the new dispensation of any of the selected medications within 7 days of hospital discharge.Results: Prescription without documented indication occurred across all medication classes, from 12,209 patients (1.4 %) for antipsychotic medications to 34,140 patients (6.1 %) for gastric acid suppressants. Risk factors for unintentional continuation varied across medication groups, but rates were consistently higher for older patients, those with multiple comorbidities, and emergency hospitalizations. The largest absolute risk factor across all medications was a hospitalization > 7 days [OR 2.03 (95 % CI 1.94-2.11) for respiratory inhalers, 6.35 (95 % CI 5.91-6.82) for antipsychotic medications]. These medications were often continued at 1 year of follow-up, and accounted for a total additional medication cost of over CAD$18 million for the study population.Conclusion: Discharged patients are at risk of being prescribed and dispensed medications that are typically intended to prevent or treat complications of acute illness, despite having no documented indication for chronic use. [ABSTRACT FROM AUTHOR]

Background In Ontario, approximately $3.8 billion is spent annually on publicly funded drug programs. The annual growth in Ontario Public Drug Program ( OPDP) expenditure has been limited to 1.2% over the course of 3 years. Concurrently, the Ontario Drug Policy Research Network ( ODPRN) was appointed to conduct drug class review research relating to formulary modernization within the OPDP. Drug class reviews by ODPRN incorporate a novel methodological technique called reimbursement-based economics, which focuses on reimbursement strategies and may be particularly relevant for policy-makers. Objectives To describe the reimbursement-based economics approach. Methods Reimbursement-based economics aims to identify the optimal reimbursement strategy for drug classes by incorporating a review of economic literature, comprehensive budget impact analyses, and consideration of cost-effectiveness. This 3-step approach is novel in its focus on the economic impact of alternate reimbursement strategies rather than individual therapies. Results The methods involved within the reimbursement-based approach are detailed. To facilitate the description, summary methods and findings from a recent application to formulary modernization with respect to the drug class tryptamine-based selective serotonin receptor agonists (triptans) used to treat migraine headaches are presented. Conclusions The application of reimbursement-based economics in drug policy reforms allows policy-makers to consider the cost-effectiveness and budget impact of different reimbursement strategies allowing consideration of the trade-off between potential cost savings vs increased access to cost-effective treatments. [ABSTRACT FROM AUTHOR]

Background: The incidence of neonatal opioid withdrawal is increasing in both Canada and the United States. However, the degree to which the treatment of pain with opioids, rather than the misuse of prescription opioids or heroin, contributes to the prevalence of neonatal opioid withdrawal remains unknown. Methods: We conducted a retrospective, population-based, cross-sectional study between 1992 and 2011 in Ontario with 2 objectives. First, we determined the annual incidence of neonatal abstinence syndrome. Second, using data from a subset of women eligible for publicly funded prescription drugs, we determined what proportion of women who deliver an infant with neonatal abstinence syndrome were given a prescription for an opioid before and during pregnancy. Results: The incidence of neonatal abstinence syndrome in Ontario increased 15-fold during the study period, from 0.28 per 1000 live births in 1992 to 4.29 per 1000 live births in 2011. During the final 5 years of the study, we identified 927 deliveries of infants with neonatal abstinence syndrome to mothers who were public drug plan beneficiaries. Of these mothers, 67% had received an opioid prescription in the 100 days preceding delivery, including 53.3% who received methadone, an increase from 28.6% in the interval spanning 1 to 2 years before delivery (p < 0.001). Prescription for nonmethadone opioids decreased from 38% to 17% (p < 0.001). Interpretation: The incidence of neonatal opioid withdrawal in Ontario has increased substantially over the last 20 years. Most of the women in this cohort who delivered an infant with neonatal abstinence syndrome had received a prescription for an opioid both before and during their pregnancy. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Chlorthalidone Versus Hydrochlorothiazide for the Treatment of Hypertension in Older Adults in Population-Based Cohort Study," by I. A. Dhalla et al. in the 2013 issue of "Annals of Internal Medicine."

Background: Some evidence suggests that chlorthalidone may be superior to hydrochlorothiazide for the treatment of hypertension. Objective: To compare the effectiveness and safety of chlorthali-done and hydrochlorothiazide in older adults. Design: Propensity score-matched observational cohort study with up to 5 years of follow-up. Setting: Ontario, Canada. Patients: All individuals aged 66 years or older who were newly treated with chlorthalidone or hydrochlorothiazide and were not hospitalized for heart failure, stroke, or myocardial infarction in the prior year were eligible for inclusion. Each chlorthalidone recipient was matched to up to 2 hydrochlorothiazide recipients on the basis of age, sex, year of treatment initiation, and propensity score. Measurements: The primary outcome was a composite of death or hospitalization for heart failure, stroke, or myocardial infarction. Safety outcomes included hospitalization with hypokalemia or hyponatremia. Results: A total of 29 873 patients were studied. During follow-up, chlorthalidone recipients (n = 10 384) experienced the primary out-come at a rate of 3.2 events per 100 person-years of follow-ip, and hydrochlorothiazide recipients experienced 3.4 events per 100 person-years of follow-up (adjusted hazard ratio, 0.93 [95% CI, 0.81 to 1.06]). Patients treated with chlorthalidone were more likely to be hospitalized with hypokalemia (adjusted hazard ratio, 3.06 [CI, 2.04 to 4.58]) or hyponatremia (adjusted hazard ratio, 1.68 [CI, 1.24 to 2.28]). In 9 post hoc analyses comparing patients initially prescribed 12.5, 25, or 50 mg of chlorthalidone per day with those prescribed 12.5, 25, or 50 mg of hydrochlorothiazide per day, the former were more likely to be hospitalized with hy-pokalemia for all 6 comparisons in which a statistically significant association was found. The results of other effectiveness and safety outcomes were also consistent with those of the main analysis. Limitation: Unmeasured differences in baseline characteristics or physician treatment approaches or an insufficiently large sample may have limited the ability to detect small differences in the comparative effectiveness of the drugs. Conclusion: As typically prescribed, chlorthalidone in older adults was not associated with fewer adverse cardiovascular events or deaths than hydrochlorothiazide. However, it was associated with a greater incidence of electrolyte abnormalities, particularly hypokalemia. Primary Funding Source: Ontario Ministry of Health and Long-Term Care. [ABSTRACT FROM AUTHOR]

The article discusses the findings of a study to investigate the association between antihypertensive drug treatment and hip fracture risk in elderly patients. It notes that the community-based research was conducted for 301,591 elderly patients in Ontario, Canada with hip fracture occurrences between April 1, 2000 to March 31, 2009. The study confirms a 43 percent increased risk for hip fractures among elderly patients in the first 45 days of receiving antihypertensive drugs.

The article discusses a study which characterized the risk of hyperkalemia-associated hospitalization in elderly patients who were being treated with trimethoprim-sulfamethoxazole. Trimethoprim-sulfamethoxazole was coprescribed with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). The population-based, nested case-control study involved a cohort of elderly patients 66 years or older from Ontario. Trimethoprim-sulfamethoxazole was associated with increased risk of hyperkalemia-associated hospitalization.

Inhaled tobramycin solution is indicated for use in the management of Pseudomonas aeruginosa in patients with cystic fibrosis (CF). Concerns have been raised regarding increasing off-label use of inhaled tobramycin, particularly for the management of COPD. We conducted an 8-year repeated cross-sectional study examining the indication for prescription claims for inhaled tobramycin in Ontario paid for by the Public Drug Benefit Program, which covers all Ontario residents with financial needs or aged 65 and older. Inhaled tobramycin prescription claims increased approximately 3 times greater from 86 prescriptions in the second quarter of 2007 to 261 prescriptions in the first quarter of 2015. Approximately half of all prescriptions (range: 46-65%) per quarter were dispensed to patients with CF. A large proportion of prescriptions (range: 31-36%) were dispensed to individuals who did not have a diagnosis of CF but had a diagnosis of COPD. In 2014, there were 324 unique users of inhaled tobramycin solution in the Ontario Public Drug Program (OPDP). Only half of users (54%; n=163) had a diagnosis of CF. Our study found increasing prescriptions of inhaled tobramycin from 2007 to 2015 in the OPDP with approximately half of these claims being for off-label use, mostly among patients with COPD. [ABSTRACT FROM AUTHOR]

The article reports on the study on the occurrence of discontinuation of long-term medication use during discharge from the hospital to the community. Patients prescribed long-term therapy with warfarin were at risk for potentially unintended medication discontinuation after elective procedures. Patients prescribed statins or ßblocker opthalmic drops were not at increased risk.

Rationale Observational cohort studies are frequently used to measure the impact of therapies on the time to a particular outcome. Treatment often has a time-variant nature since it is frequently initiated at varying times during a patient’s follow-up. Studies in the medical literature frequently ignore the time-dependent nature of treatment exposure. Survivor treatment bias can arise when the time dependent nature of treatment exposure is ignored since patients who survived to receive treatment may be healthier than patients who died prior to receipt of treatment. Aims and objectives The objective of the current study was to explicitly quantify the magnitude of survivor-treatment bias. Methods Monte Carlo simulations using parameters obtained from an analysis of patients admitted to hospital with a diagnosis of acute myocardial infarction in Ontario, Canada. Results and conclusions When the true treatment was null (hazard ratio of 1), estimated treatment effects varied from a 4% reduction in mortality to a reduction in mortality of 27% when the time varying nature of the treatment was ignored. Furthermore, survivor-treatment bias increased as the time required foe exposed patients to receive treatment increased. Similarly, survivor treatment bias was amplified as exposure was defined to be exposure at any time prior to mortality compared to exposure within a fixed time interval starting at the time origin. Ignoring the time-dependent nature of treatment results in overly optimistic estimates of treatment effects. Depending on the period required for patients to initiate therapy, treatments with no effect on survival can appear to be strongly associated with improved survival. The current study is the first to explicitly quantify the magnitude of bias that results from ignoring the time-varying nature of treatment exposure in survival studies. [ABSTRACT FROM AUTHOR]

Background Atypical antipsychotic agents are thought to be less likely than older typical agents to produce parkinsonism. This has not been well documented. We compared the risk of development of incident parkinsonism among older adults dispensed atypical relative to typical antipsychotics. Methods Retrospective cohort study of all adults 66 years and older in Ontario. We used Cox proportional hazards models to study the association between the type, potency, and dose of antipsychotic dispensed and the development of parkinsonism during 1 year of follow-up. Results All 25 769 older adults prescribed antipsychotics were observed for 11 573 person-years, and 449 events of parkinsonism were identified. Relative to individuals dispensed an atypical antipsychotic, those dispensed a typical agent were 30% more likely (adjusted hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.04-1.58) and those exposed to neither agent were 60% less likely (HR, 0.40; 95% CI, 0.29-0.43) to experience development of parkinsonism. Furthermore, those dispensed lower-potency typical agents were no different (HR, 0.75; 95% CI, 0.48-1.15), and those dispensed higher-potency typical antipsychotics were at close to a 50% greater risk (HR, 1.44; 95% CI, 1.13-1.84) of development of parkinsonism relative to atypical antipsychotics. Relative to those dispensed a high-dose atypical antipsychotic, those dispensed a typical antipsychotic were at similar risk for parkinsonism (Wald χ2 = 0.14, P = .7). Conclusions The risk of development of parkinsonism associated with the use of high-dose atypical antipsychotics was similar to that associated with the use of typical antipsychotics. Caution should be used when prescribing atypical antipsychotic therapy at high doses. [ABSTRACT FROM AUTHOR]

Objective: To explore the prescribing of potentially inappropriate drug therapy in Ontario, Canada where there is a restrictive drug formulary relative to the US where there is no single drug formulary. Methods: A retrospective, cohort study using an administrative database (Ontario, Canada) compared with published survey results (US). All 1 088 680 community-dwelling adults ≥66 years of age in Ontario, Canada compared with published survey results from 2455 community-dwelling older adults in the US in 1996. Patterns of potentially inappropriate drug prescribing were compared between countries using a list of 33 potentially inappropriate drug therapies. These therapies were classified by an expert panel into three categories: (i) those to always avoid; (ii) those which are rarely appropriate; and (iii) those with only some indications to prescribe. Results: Among the 33 potentially inappropriate drug therapies, 15 (45%) prescribed in the US were not available through Ontario’s drug formulary. Potentially inappropriate drug therapies available through the Ontario Drug Benefit Plan (ODB) and also in the US were frequently prescribed in both Ontario and the US. Differences in prescribing patterns of individual drug therapies were noted between the two countries. Specifically, in the rarely appropriate category, diazepam, a long half-life benzodiazepine, was much more frequently dispensed in Ontario than in the US (3.18% vs 1.37%). In contrast, dextropropoxyphene, an opioid with a poor adverse event profile was more frequently prescribed in the US than in Ontario (6.21% vs 0.74%). Conclusion: Almost half of the potentially inappropriate drug therapies that are available in the US are unavailable from Ontario’s drug formulary. Potentially inappropriate drug therapies that were available through the ODB were frequently prescribed in both countries. Alternative approaches that make information immediately accessible to physicians at the time they make prescribing decisions should be considered to improve prescribing practices. [ABSTRACT FROM AUTHOR]

Context The benefits of cardiovascular therapies such as statins for secondary prevention have been well documented, although they may not be optimally used in patients most likely to benefit. Ideally, aggressiveness in the use of these beneficial therapies should correlate with baseline cardiovascular risk. Objective To examine the association between physicians' treatment aggressiveness and baseline cardiovascular risk. Design, Setting, and Patients Retrospective cohort study incorporating the use of multiple linked health care administrative databases covering more than 1.4 million elderly residents of Ontario. We included 396 077 patients aged 66 years or older who had a history of cardiovascular disease or diabetes while undergoing medical treatment and who were alive on April 1, 1998. Baseline cardiovascular risk was derived using a risk-adjustment index in which we modeled probability of death after 3 years of follow-up. Main Outcome Measure Likelihood of statin use, stratified by baseline cardiovascular risk, after adjusting for age, sex, socioeconomic status, and rural or urban residence. Results Only 75 617 patients (19.1%) in this secondary prevention cohort were prescribed statins. In patients 66 to 74 years old, the adjusted probabilities of statin prescription were 37.7%, 26.7%, and 23.4% in the categories of low, intermediate, and high baseline risk, respectively. The likelihood of statin prescription was 6.4% lower (adjusted odds ratio, 0.94; 95% confidence interval, 0.93-0.95) for each year of increase in age and each 1% increase in predicted 3-year mortality risk. The influence of age also interacted synergistically with baseline risk on the prescription of statins (P<.001). Conclusions We found that prescription of statins diminished progressively as baseline cardiovascular risk and future probability of death increased. Since the benefits of a therapy are dependent on the baseline risk, the maximum benefits of statins may not be fully realized... [ABSTRACT FROM AUTHOR]

: PurposePrevious guidelines for the management of uncomplicated hypertension in elderly patients have recommended diuretic agents and then beta-blockers. We examined trends in the initial treatment choice for elderly people with hypertension and the effects of a government-sponsored program to publish and disseminate a simplified version of the national guidelines for the treatment of hypertension to all physicians in Ontario, Canada.: Subjects and methodsLinked administrative databases containing information on the more than 1.2 million elderly residents in Ontario were used. Time series analysis was performed to determine prescribing trends from 1993 to 1998 for patients who began antihypertensive medication for the treatment of hypertension and to examine the effects of the simplified guidelines that were distributed in July of 1995.: ResultsDiuretic agents were the most commonly prescribed medications, with annual rates from 35% to 38% (P = 0.59) throughout the study. Beta-blocker prescribing rose from 12% to 16% (P <0.01), whereas angiotensin-converting enzyme (ACE) inhibitor prescribing rose from 27% to 32% (P <0.01). Prescriptions for calcium channel blockers dropped significantly, from 23% to 14% (P <0.01). However, the publication and dissemination of the Ontario hypertension guidelines had no statistically significant effects on the proportion of patients who began treatment with a diuretic agent (P = 0.55), beta-blocker, (P = 0.32), ACE inhibitor (P = 0.09), or calcium channel blocker (P = 0.07).: ConclusionThe dissemination of simplified practice guidelines for hypertension did not have notable effects on prescribing patterns in Ontario. [Copyright &y& Elsevier]

The article reports on research which was conducted to investigate whether the use of cholinesterase inhibitors (ChEIs) was associated with a risk of upper gastrointestinal bleeding in elderly adults with dementia. Researchers evaluated 203,279 dementia patients. They found that there was no significant association between ChEIs and bleeding in elderly adults.

Presents a research letter on the changes in prescribing patterns following publication of the ALLHAT Trial which studied treatment for hypertension to prevent heart attacks. Study of various antihypertensive agents; Methods of the study; Results; Comments from the authors.

Presents a study examining the effects of changing prescription patterns of lithium and valproic acid in old age. Use of valproic acid as an alternative to lithium for treating bipolar disorder in North America; Questioning of the effectiveness of both drugs in elderly patients; Description of the methods and results of the study.

Introduction: Medication is an important option for patients with overactive bladder (OAB), with four different drugs approved over the last 10 years, including the first non-anticholinergic treatment, mirabegron. We set out to describe the number and rate of users of medication for the management of OAB over the last 15 years among residents of Ontario, Canada covered by the public drug programs. Methods: We conducted a population-based, repeated cross-sectional study examining quarterly publically funded prescription claims for OAB medications from January 2000 to June 2016 in Ontario, Canada. Results: We report two major changes in prescription patterns for OAB. The first was the rise of newer, more selective anticholinergics (tolterodine, solifenacin, and darifenacin) replacing oxybutynin. This led to a 54.8% reduction in the rate of users of oxybutynin over the study period from 10.4 users/1000 beneficiaries in 2000 to 4.7 users/1000 beneficiaries in 2016. Recently, we saw the emergence of mirabegron as the most commonly prescribed treatment for OAB. By the final quarter of the observation period, mirabegron was the most commonly used OAB treatment with 25.0% (n=19 411) of all OAB medication users in Ontario (n=77 660). Conclusions: Our findings highlight the rapid uptake of novel agents and a major shift in the treatment of OAB over the last three years. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. N Engl J Med 2006;354:1352-61. [ABSTRACT FROM AUTHOR]