Factors Associated With Off-Label Utilization of Second-Generation Antipsychotics Among Publicly Insured Adults.

OBJECTIVE: Off-label utilization of second-generation antipsychotic medications may expose patients to significant risks. The authors examined the prevalence, temporal trends, and factors associated with off-label utilization of second-generation antipsychotics among publicly insured adults. METHODS: A retrospective repeated panel was used to examine monthly off-label utilization of second-generation antipsychotics among fee-for-service Medicare, Medicaid, and dually eligible White, Black, and Latino adult beneficiaries filling prescriptions for second-generation antipsychotics in California, Georgia, Mississippi, and Oklahoma from July 2008 through June 2013. RESULTS: Among 301,367 users of second-generation antipsychotics, between 36.5% and 41.9% had utilization that was always off-label. Payer did not modify effects of race-ethnicity on off-label utilization. Compared with Whites, Blacks had lower monthly odds of off-label utilization in all four states, and Latinos had lower odds of utilization in California and Georgia. Payer was associated with off-label utilization in California, Mississippi, and Oklahoma. California Medicaid beneficiaries were 1.12 (95% confidence interval=1.10-1.13) times as likely as dually eligible beneficiaries to have off-label utilization. Off-label utilization increased relative to the baseline year in all states, but a downward trend followed in three states. CONCLUSIONS: Off-label utilization of second-generation antipsychotics was prevalent despite the drugs' cardiometabolic risks and little evidence of their effectiveness. The lower likelihood of off-label utilization among patients from racial-ethnic minority groups might stem from prescribers' efforts to minimize risks, given a higher baseline risk for these groups, or from disparities-associated factors. Variation among payers suggests that payer policies can affect off-label utilization.

Impact of Primary Care Worksite Health and Wellness Clinics on HbA1c Level Among Prediabetic or Diabetic Employees.

PURPOSE: To determine whether the use of worksite health and wellness clinics reduced hemoglobin A1c (HbA1c) for prediabetic and diabetic employees. DESIGN: Hemoglobin A1c values were compared between clinic users and matched non-users. SETTING: The Wonderful Company's (TWC's) agricultural and packaging sites in Central California. SAMPLE: TWC's 2016 to 2017 employees who used clinics (n = 445, defined below) and clinic non-users (n = 217) who had HbA1c screening and worked at TWC for 3 or more months each year. INTERVENTION: A unique worksite health and wellness clinic that offers multidisciplinary primary medical care in synergy with TWC's overall wellness programs. MEASURES: Exposure was clinic use, defined by frequency and patterns of visits. Hemoglobin A1c was the outcome of interest. ANALYSIS: Users and non-users were propensity score matched using the 2016 employee data including HbA1c, and then 2017 HbA1c values were compared between the 2 groups. RESULTS: The 2017 HbA1c of diabetic employees was lower among clinic users compared to non-users (7.42 vs 8.53, P < .001). Differences in HbA1c among prediabetics or diabetics and prediabetics aggregated were not statistically significant, despite TWC's population-level data showing a reduction in prediabetes prevalence. The clinic impact results were robust to multivariate analyses and an alternative definition of utilization. CONCLUSION: The implementation of TWC's Health and Wellness clinics was associated with reductions in HbA1c among diabetics, but further research is needed on prediabetics.

The Effects of Dementia Care Co-Management on Acute Care, Hospice, and Long-Term Care Utilization.

BACKGROUND/OBJECTIVES: Although nurse practitioner dementia care co-management has been shown to reduce total cost of care for fee-for-service (FFS) Medicare beneficiaries, the reasons for cost savings are unknown. To further understand the impact of dementia co-management on costs, we examined acute care utilization, long-term care admissions, and hospice use of program enrollees as compared with persons with dementia not in the program using FFS and managed Medicare claims data. DESIGN: Quasi-experimental controlled before-and-after comparison. SETTING: Urban academic medical center. PARTICIPANTS: A total of 856 University of California, Los Angeles (UCLA) Alzheimer's and Dementia Care program patients were enrolled between July 1, 2012, and December 31, 2015, and 3,139 similar UCLA patients with dementia not in the program. Comparison patients were identified as having dementia using International Classification of Diseases-9 codes and natural language processing of clinical notes. Coarsened exact matching was used to reduce covariate imbalance between intervention and comparison patients. INTERVENTION: Dementia co-management model using nurse practitioners partnered with primary care providers and community organizations. MEASUREMENTS: Average difference-in-differences per quarter over the 2.5-year intervention period for all-cause hospitalization, emergency department (ED) visits, intensive care unit (ICU) stays, and number of inpatient hospitalization days; admissions to long-term care facilities; and hospice use in the last 6 months of life. RESULTS: Intervention patients had fewer ED visits (odds ratio [OR] = .80; 95% confidence interval [CI] = .66-.97) and shorter hospital length of stay (incident rate ratio = .74; 95% CI = .55-.99). There were no significant differences between groups for hospitalizations or ICU stays. Program participants were less likely to be admitted to a long-term care facility (hazard ratio = .65; 95% CI = .47-.89) and more likely to receive hospice services in the last 6 months of life (adjusted OR = 1.64; 95% CI = 1.13-2.37). CONCLUSION: Comprehensive nurse practitioner dementia care co-management reduced ED visits, shortened hospital length of stay, increased hospice use, and delayed admission to long-term care.

Receipt of Promotional Payments at the Individual and Physician Network Level Associated with Higher Branded Antipsychotic Prescribing Rates.

Pharmaceutical promotion can lead to market size expansion, which is beneficial if previously untreated patients access treatment but deleterious if it leads to overuse, an area of concern for second generation antipsychotics (SGA). We contribute to a growing body of work suggesting that networks of social and professional relationships shape prescribing behavior. We examined 88,439 Medicare Part D prescribing physicians, finding that promotion is associated with SGA market size expansion (elasticity: 0.062) and that network-level promotional activity is associated with network members' branded product prescribing. Research on the effects of promotion should account for its effects in prescribers' networks.

Evaluation of Policy Options for Increasing the Availability of Primary Care Services in Rural Washington State.

The Washington State legislature has recently considered several policy options to address a perceived shortage of primary care physicians in rural Washington. These policy options include opening the new Elson S. Floyd College of Medicine at Washington State University in 2017; increasing the number of primary care residency positions in the state; expanding educational loan-repayment incentives to encourage primary care physicians to practice in rural Washington; increasing Medicaid payment rates for primary care physicians in rural Washington; and encouraging the adoption of alternative models of primary care, such as medical homes and nurse-managed health centers, that reallocate work from physicians to nurse practitioners (NPs) and physician assistants (PAs). RAND Corporation researchers projected the effects that these and other policy options could have on the state's rural primary care workforce through 2025. They project a 7-percent decrease in the number of rural primary care physicians and a 5-percent decrease in the number of urban ones. None of the policy options modeled in this study, on its own, will offset this expected decrease by relying on physicians alone. However, combinations of these strategies or partial reallocation of rural primary care services to NPs and PAs via such new practice models as medical homes and nurse-managed health centers are plausible options for preserving the overall availability of primary care services in rural Washington through 2025.

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.

Blood transfusion and coagulopathy in geriatric trauma patients.

BACKGROUND: Trauma resuscitation has undergone a paradigm shift with new emphasis on the early use of blood products and increased proportions of plasma and platelets. However, it is unclear how this strategy is applied or how effective it is in the elderly population. The study aim is to identify differences in transfusion practices and the coagulopathy of trauma in the elderly. METHODS: Data was prospectively collected on all consecutive patients that met trauma activation criteria at a Level I trauma centre. Data fields included patient demographics, co-morbidities, injury and resuscitation data, laboratory values, thromboelastography (TEG) results, and outcome measures. Elderly patients were defined as those 55 and older. Propensity-score matched analysis was completed for patients receiving blood product transfusion. Patients were matched by gender, mechanism, injury severity score (ISS), head injury, and time from injury. RESULTS: Total of 628 patients were included, of which 142 (23%) were elderly. Elderly patients were more likely to be female (41% vs. 24%), suffer blunt mechanism of trauma (96% vs. 80%), have higher ISS scores (mean 25.4 vs. 21.6) and mortality (19% vs. 8%). Elderly patients were significantly more likely to receive a blood transfusion (42% vs. 30%), specifically for red cells and plasma. Propensity-matched analysis resulted in no difference in red cell transfusion or mortality. Despite the broad similarities between the matched cohorts, trauma coagulopathy as measured by TEG was less commonly observed in the elderly. DISCUSSION: Our results suggest that elderly trauma patients are more likely to receive blood products when admitted to a trauma centre, though this may be attributed to under-triage. The results also suggest an altered coagulopathic response to traumatic injury which is partially influenced by increased anticoagulant and antiplatelet medication use in the geriatric population. CONCLUSION: It is not clear whether the acute coagulopathy of trauma is equivalent in geriatric patients, and further study is therefore warranted.

Language Barriers Among the Foreign-Born in Canada: Agreement of Self-Reported Measures and Persistence Over Time.

Persistent language barriers are associated with poor health outcomes. The agreement between reporting a language barrier at time of immigration and in the 2007-2008 Canadian Community Health Survey (CCHS) was calculated using kappa scores among foreign-born individuals who arrived to Ontario, Canada between 1985 and 2005. A total of 2323 immigrants were included, with a mean (± SD) time of 10.2 ± 6.4 years between immigration and completing the CCHS. Only 6 % of immigrants reported a persistent language barrier, resulting in a low agreement between the two sources (kappa = 0.06, 95 % CI 0.042-0.086). Though immigrants were less likely to report a persistent language barrier the longer they had been in Canada, only 13 % of immigrants who had arrived <2 years ago reported one. Self-reported language barriers at time of immigration are poor indicators of persistent language barriers. There is a need for a better measure of language barriers among Canadian immigrants.

Drug-prescribing patterns among optometrists and nonophthalmologist physicians at a tertiary care centre in Kingston, Ontario.

OBJECTIVE: To report on patterns of optometry prescribing and adherence to prescribing regulations at a tertiary care ophthalmology centre. DESIGN: Prospective cohort study. PARTICIPANTS: All new referrals from optometrists and other health care professionals to the emergency eye care service (n = 1965) between July 2011 and June 2012, as well as optometry referrals to 2 subspecialty services (glaucoma [n = 71] and cornea [n = 212]). METHODS: In our primary analysis, the frequency of prescribing and classes of medications prescribed were reported and compared amongst various referral sources to the emergency eye care service. As a secondary analysis, we reported frequency of prescribing in optometry referrals to 2 subspecialty clinics. Adherence to prescribing guidelines was reported for all optometry referrals. RESULTS: Of 296 referrals from optometrists to the emergency eye care service, 20 (6.8%) had received a prescription medication; this was significantly less compared to emergency and family physicians (p < 0.001). Topical antibiotics were the most frequently prescribed medication class. The frequency of prescribing by optometrists was 5.2% (11/212) and 4.2% (3/71) for patients referred to the cornea and glaucoma services, respectively. Among those patients referred after being given a prescription for a glaucoma medication by an optometrist, 89% cases (8/9) did not adhere to prescribing regulations. CONCLUSIONS: After the introduction of prescribing privileges, optometrists prescribe a variety of medications in their practices. Current prescribing guidelines are not always followed in practice, suggesting that continued study and collaboration is necessary to create an optimal model of interdisciplinary care that provides access to the highest quality of care.

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.

Long-term outcomes following self-poisoning in adolescents: a population-based cohort study.

BACKGROUND: Suicide is the third most common cause of death among adolescents worldwide, and poisoning is the leading method of attempted suicide. Unlike more violent methods, survival after self-poisoning is common, providing an opportunity for secondary prevention. We determined the risk and time course of completed suicide after adolescent self-poisoning, and explored potential risk factors. METHODS: We did a population-based cohort study using multiple linked health-care databases in Ontario, Canada, from Jan 1, 2001, to Dec 31, 2012. We identified all adolescents aged 10-19 years presenting to hospital after a first self-poisoning episode. Each was matched with 50 population-based reference individuals with no such history, matching on age, sex, and year of cohort entry. The primary outcome was the risk of suicide after a first self-poisoning episode. Secondary analyses explored factors associated with suicide and self-poisoning repetition. FINDINGS: We identified 20,471 adolescents discharged from hospital after a first self-poisoning episode and 1,023,487 matched reference individuals. Over a median follow-up of 7·2 years (IQR 4·2-9·7), 248 (1%) adolescents discharged after self-poisoning died, 126 (51%) of whom died by suicide. The risk of suicide at 1 year after self-poisoning was greatly increased relative to reference individuals (hazard ratio [HR] 32·1, 95% CI 23·6-43·6), corresponding to a suicide rate of 89·6 (95% CI 75·2-106·7) per 100,000 person-years over the course of follow-up. The median time from hospital discharge to suicide was 3·0 years (IQR 1·1-5·3). Factors associated with suicide included recurrent self-poisoning (adjusted HR 3·5, 95% CI 2·4-5·0), male sex (2·5, 1·8-3·6) and psychiatric care in the preceding year (1·7, 1·1-2·5). Adolescents admitted to hospital for self-poisoning were also more likely to die from accidents (5·2, 4·1-6·6) and from all causes (3·9, 2·8-5·4) during follow-up. INTERPRETATION: Self-poisoning in adolescence is a strong predictor of suicide and premature death in the ensuing decade, and identifies a high-risk group for targeted secondary prevention. Suicide risk is increased for many years after the index hospital admission, emphasising the importance of sustained prevention efforts. FUNDING: The Canadian Drug Safety and Effectiveness Research Network, Ontario Ministry of Health and Long-Term Care, Paediatric Consultants Partnership.

Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study.

BACKGROUND: Proton pump inhibitors (PPIs) cause interstitial nephritis and are an underappreciated cause of acute kidney injury. We examined the risk of acute kidney injury and acute interstitial nephritis in a large population of older patients receiving PPIs. METHODS: We conducted a population-based study involving Ontario residents aged 66 years and older who initiated PPI therapy between Apr. 1, 2002, and Nov. 30, 2011. We used propensity score matching to establish a highly comparable reference group of control patients. The primary outcome was hospital admission with acute kidney injury within 120 days, and a secondary analysis examined acute interstitial nephritis. We used Cox proportional hazards regression to adjust for differences between groups. RESULTS: We studied 290 592 individuals who commenced PPI therapy and an equal number of matched controls. The rates of acute kidney injury (13.49 v. 5.46 per 1000 person-years, respectively; hazard ratio [HR] 2.52, 95% CI 2.27 to 2.79) and acute interstitial nephritis (0.32 vs. 0.11 per 1000 person-years; HR 3.00, 95% CI 1.47 to 6.14) were higher among patients given PPIs than among controls. INTERPRETATION: In our study population of older adults, those who started PPI therapy had an increased risk of acute kidney injury and acute interstitial nephritis. These are potentially reversible conditions that may not be readily attributed to drug treatment. Clinicians should appreciate the risk of acute interstitial nephritis during treatment with PPIs, monitor patients appropriately and discourage the indiscriminate use of these drugs.

Rates of Anomalous Bupropion Prescriptions in Ontario, Canada.

PURPOSE: Reports of bupropion misuse have increased since it was first reported in 2002. The purpose of this study was to explore trends in bupropion prescribing suggestive of misuse or diversion in Ontario, Canada. METHODS: A serial cross-sectional study was conducted of Ontarians aged younger than 65 years who received prescriptions under Ontario's public drug program from April 1, 2000, to March 31, 2013. We determined the number of potentially inappropriate prescriptions in each quarter, defined as early refills dispensed within 50% of the duration of the preceding prescription, as well as potentially duplicitous prescriptions, defined as similarly early refills originating from a different prescriber and different pharmacy. We replicated these analyses for citalopram and sertraline, antidepressants not known to be prone to abuse. RESULTS: We identified 1,780,802 prescriptions for bupropion, 3,402,462 for citalopram, and 1,775,285 for sertraline. Rates of early refills for bupropion declined during the study from 4.8% to 3.1%. In the final quarter, rates of early refills for bupropion were more common than for citalopram (3.1% vs 2.2%) (P <.001) but not for sertraline (3.1% vs 2.9%) (P =.16). Potentially duplicitous prescriptions for bupropion increased dramatically, from <0.05% of all prescriptions in early 2000 to 0.47% in early 2013 and by the final quarter were more common than both citalopram (0.11%) and sertraline (0.12%) (P <.001). CONCLUSIONS: Although no marked differences were seen for early refills of bupropion relative to its comparators, potentially duplicitous prescriptions have increased dramatically in Ontario, suggesting growing misuse of the drug.

Risk of cardiovascular events and mortality among a population-based cohort of immigrants and long-term residents with diabetes: Are all immigrants healthier and if so, for how long?

BACKGROUND: Cardiovascular events are responsible for half of all deaths among individuals with diabetes. Immigrants to Western countries may experience an acceleration of cardiovascular risk in the first 10 years of arrival because of a sedentary lifestyle, poor diet, or barriers to accessing care, leading to higher levels of obesity and diabetes. OBJECTIVES: To compare the risk of cardiovascular events and mortality between immigrants to Canada and long-term residents with diabetes and to assess whether immigrants experience acceleration in risk after arrival. METHODS: We conducted a population-based retrospective cohort study using linked health and immigration data from Ontario, Canada, of 87,707 immigrants who immigrated to Canada between 1985 and 2005 matched to 87,707 long-term residents with diabetes (age ≥20 years). Individuals were followed up from April 1, 2005, until February 29, 2012, for the primary composite outcome of a cardiovascular event (acute myocardial infarction, unstable angina, congestive heart failure, transient ischemic attack, stroke) or all-cause mortality. RESULTS: There was a lower adjusted risk of cardiovascular events or mortality among immigrants (adjusted hazard ratio [HR] 0.76, 95% CI 0.74-0.78) after accounting for differences in baseline age, gender, socioeconomic status, neighborhood, and health care utilization-which persisted beyond 10 years from immigration. However, this healthy immigrant advantage was not found among more recent refugees (HR 0.93, 95% CI 0.81-1.08), immigrants with no previous education (HR 1.08, 95% CI 0.84-1.40), and those who were unmarried (HR 0.80, 95% CI 0.62-1.03). CONCLUSION: Immigrants with diabetes are at lower risk for cardiovascular events and mortality compared with long-term residents, an effect that persists more than 10 years after arrival. Not all immigrants demonstrate this health advantage.

Risk of Suicide Following Deliberate Self-poisoning.

IMPORTANCE: Suicide is the tenth leading cause of death in the United States, and its rate has risen by 16% in the past decade. Deliberate self-poisoning is the leading method of attempted suicide. Unlike more violent methods, which are almost universally fatal, survival following self-poisoning is common, providing an opportunity for secondary prevention. However, the long-term risk of suicide following a first episode of self-poisoning is unknown. OBJECTIVE: To determine the risk of suicide and mortality from other causes following a first self-poisoning episode. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study using multiple linked health care databases. We identified all individuals with a first self-poisoning episode in Ontario, Canada, from April 1, 2002, through December 31, 2010, and followed up all surviving participants until December 31, 2011, or death, whichever occurred first. For each individual with a deliberate self-poisoning episode, we randomly selected 1 control from the same population with no such history, matched for age (within 3 months), sex, and calendar year. MAIN OUTCOMES AND MEASURES: The primary analysis examined the risk of suicide following discharge after self-poisoning. The secondary analyses explored factors associated with suicide and examined the risk of death caused by accidents or any other cause. RESULTS: We identified 65 784 patients (18 482 [28.1%] younger than 20 years) who were discharged after a first self-poisoning episode. During a median follow-up of 5.3 years (interquartile range, 3.1-7.6 years), 4176 died, including 976 (23.4%) by suicide. The risk of suicide following self-poisoning was markedly increased relative to controls (hazard ratio, 41.96; 95% CI, 27.75-63.44), corresponding to a suicide rate of 278 vs 7 per 100 000 person-years, respectively. The median time from hospital discharge to completed suicide was 585 days (interquartile range, 147-1301 days). Older age, male sex, multiple intervening self-poisoning episodes, higher socioeconomic status, depression, and recent psychiatric care were strongly associated with suicide. Patients with a self-poisoning episode were also more likely to die because of accidents (hazard ratio, 10.45; 95% CI, 8.10-13.47) and all causes combined (hazard ratio, 5.55; 95% CI, 5.12-6.02). CONCLUSIONS AND RELEVANCE: A first self-poisoning episode is a strong predictor of subsequent suicide and premature death. Most suicides occur long after the index poisoning, emphasizing the importance of longitudinal, sustained secondary prevention initiatives.

Trimethoprim-sulfamethoxazole and risk of sudden death among patients taking spironolactone.

BACKGROUND: Trimethoprim-sulfamethoxazole increases the risk of hyperkalemia when used with spironolactone. We examined whether this drug combination is associated with an increased risk of sudden death, a consequence of severe hyperkalemia. METHODS: We conducted a population-based nested case-control study involving Ontario residents aged 66 years or older who received spironolactone between Apr. 1, 1994, and Dec. 31, 2011. Within this group, we identified cases as patients who died of sudden death within 14 days after receiving a prescription for trimethoprim-sulfamethoxazole or one of the other study antibiotics (amoxicillin, ciprofloxacin, norfloxacin or nitrofurantoin). For each case, we identified up to 4 controls matched by age and sex. We determined the odds ratio (OR) for the association between sudden death and exposure to each antibiotic relative to amoxicillin, adjusted for predictors of sudden death using a disease risk index. RESULTS: Of the 11,968 patients who died of sudden death while receiving spironolactone, we identified 328 whose death occurred within 14 days after antibiotic exposure. Compared with amoxicillin, trimethoprim-sulfamethoxazole was associated with a more than twofold increase in the risk of sudden death (adjusted OR 2.46, 95% confidence interval [CI] 1.55-3.90). Ciprofloxacin (adjusted OR 1.55, 95% CI 1.02-2.38) and nitrofurantoin (adjusted OR 1.70, 95% CI 1.03-2.79) were also associated with an increased risk of sudden death, although the risk with nitrofurantoin was not apparent in a sensitivity analysis. INTERPRETATION: The antibiotic trimethoprim-sulfamethoxazole was associated with an increased risk of sudden death among older patients taking spironolactone. When clinically appropriate, alternative antibiotics should be considered in these patients.

Trends in Excess Mortality Among Patients With Rheumatoid Arthritis in Ontario, Canada.

OBJECTIVE: To evaluate excess mortality over time, comparing rheumatoid arthritis (RA) patients with the general population. METHODS: We computed all-cause mortality rates among Ontario residents age ≥15 years with RA versus without RA from 1996 to 2009. Age- and sex-standardized mortality rates were expressed as the number of deaths per 1,000 population. Excess mortality rates were calculated as the difference between death rates among RA patients and those in the general population. We estimated standardized mortality ratios (SMRs) and mortality rate ratios (MRRs) to assess relative excess mortality over time. RESULTS: From 1996 to 2009, SMRs in RA ranged from 13.0 (95% confidence interval [95% CI] 12.2, 13.9) to 9.2 deaths per 1,000 RA patients (95% CI 8.4, 10.0); and for those without RA from 8.7 (95% CI 8.6, 8.7) to 6.0 deaths (95% CI 5.9, 6.0) per 1,000 general population. Over the study period, the excess mortality rate among RA patients was approximately 3 excess deaths per 1,000 population. Relative reductions in standardized mortality rates occurred over time for those with and without RA (-21.4% versus -13.4%). The SMRs for RA patients in 1996-1997, 2000-2001, 2004-2005, and 2008-2009 were 1.51 (95% CI 1.43, 1.59), 1.50 (95% CI 1.43, 1.57), 1.43 (95% CI 1.37, 1.50), and 1.41 (95% CI 1.35, 1.47), respectively. We did not find a significant change in the MRR by calendar time. CONCLUSION: Mortality for RA patients has decreased over time but remains elevated compared to the general population, with 40-50% more deaths among RA patients. The relative excess mortality over time (mortality gap) remains unchanged in our sample.

Development and validation of an administrative data algorithm to estimate the disease burden and epidemiology of multiple sclerosis in Ontario, Canada.

BACKGROUND: Few studies have assessed the accuracy of administrative data for identifying multiple sclerosis (MS) patients. OBJECTIVES: To validate administrative data algorithms for MS, and describe the burden and epidemiology over time in Ontario, Canada. METHODS: We employed a validated search strategy to identify all MS patients within electronic medical records, to identify patients with and without MS (reference standard). We then developed and validated different combinations of administrative data for algorithms. The most accurate algorithm was used to estimate the burden and epidemiology of MS over time. RESULTS: The accuracy of the algorithm of one hospitalisation or five physician billings over 2 years provided both high sensitivity (84%) and positive predictive value (86%). Application of this algorithm to provincial data demonstrated an increasing cumulative burden of MS, from 13,326 patients (0.14%) in 2000 to 24,647 patients in 2010 (0.22%). Age-and-sex standardised prevalence increased from 133.9 to 207.3 MS patients per 100,000 persons in the population, from 2000 - 2010. During this same period, age-and-sex-standardised incidence varied from 17.9 to 19.4 patients per 100,000 persons. CONCLUSIONS: MS patients can be accurately identified from administrative data. Our findings illustrated a rising prevalence of MS over time. MS incidence rates also appear to be rising since 2009.

Impact of language barriers on complications and mortality among immigrants with diabetes: a population-based cohort study.

OBJECTIVE: Our objective was to examine the effect of language barriers on the risk of acute and chronic complications of diabetes and on mortality among immigrants. RESEARCH DESIGN AND METHODS: Linked health and immigration databases were used to identify 87,707 adults with diabetes who immigrated to Ontario, Canada, between 1985 and 2005. These individuals were included in our cohort and stratified by language ability at the time of their immigration application. Primary end points included: one or more emergency department visit or hospitalization for 1) hypo- or hyperglycemia, skin and soft tissue infection, or foot ulcer and 2) a cardiovascular event or death between April 1, 2005, and February 29, 2012. RESULTS: Our cohort was followed up for a median of 6.9 person-years. Immigrants with language barriers were older (mean age, 49 ± 15 vs. 42 ± 13 years; P < 0.001), more likely to have immigrated for family reunification (66% vs. 38%, P < 0.001), had less education (secondary school or less and no education, 82% vs. 53%; P < 0.001), and a higher use of health care (mean visits, 8.6 ± 12.1 vs. 7.8 ± 11.2; P < 0.001). Immigrants with language barriers were not found to have higher adjusted rates of diabetes complications (acute complications: hazard ratio [HR] 0.99, 95% CI 0.93-1.05; cardiovascular events or death: HR 0.95, 95% CI 0.91-0.99). Significant predictors included older age, being unmarried, living in a rural neighborhood, and having less education. Immigrants who were older (≥65 years) and who had arrived through family reunification had a lower risk of cardiovascular events or death (HR 0.88, 95% CI 0.81-0.96). CONCLUSIONS: In a heterogenous immigrant population with universal insurance, language barriers were not found to increase the risk of diabetes complications. However, their effect may vary based on age at time of landing, education level, marital status, and neighborhood of settlement.

Intraarticular hip injection and early revision surgery following total hip arthroplasty: a retrospective cohort study.

OBJECTIVE: Therapeutic intraarticular injections are used in the management of hip osteoarthritis (OA). Some studies suggest that their use increases the risk of infection and subsequent revision surgery after primary total hip arthroplasty (THA), while others do not. We undertook this study to clarify the relationship between prior intraarticular injection and the risk of complication in a subsequent primary THA. METHODS: In a cohort of patients with hip OA who underwent a primary elective THA between 2002 and 2009, we identified those who received ≥1 intraarticular injection performed by a radiologist in the 5 years preceding their THA. Multivariable Cox proportional hazards models were used to determine the relationship between receipt of a presurgical injection (no injection, 1-5 years prior to THA, or <1 year prior to THA) and the occurrence of postsurgical joint infection and revision THA in the following 2 years, while controlling for confounders. RESULTS: Of 37,881 eligible THA recipients, 2,468 (6.5%) received an intraarticular injection performed by a radiologist within 5 years of their THA (1,691 at <1 year, 777 at 1-5 years). Controlling for age, sex, comorbidity, frailty, income, and provider volume, those who had an injection in the year preceding surgery were at increased risk of infection (adjusted hazard ratio [HR] 1.37, P = 0.03) and revision THA (adjusted HR 1.53, P = 0.03) within 2 years of the primary THA, relative to patients who did not. The association between prior injection and revision arthroplasty was attenuated and became nonsignificant (adjusted HR 1.41, P = 0.13) after occurrence of postoperative infection was controlled for in the regression model. No effect was found for injection 1-5 years prior to surgery. CONCLUSION: Intraarticular injection in the year preceding THA independently predicted increased risk of infection leading to early revision surgery. Further studies are warranted to elucidate explanations for these findings.