Tara Gomes

Risk of incident diabetes among patients treated with statins: population based study

Objective To examine the risk of new onset diabetes among patients treated with different HMG-CoA reductase inhibitors (statins). Design Population based cohort study with time to event analyses to estimate the relation between use of particular statins and incident diabetes. Hazard ratios were calculated to determine the effect of dose and type of statin on the risk of incident diabetes. Setting Ontario, Canada. Participants All patients aged 66 or older without diabetes who started treatment with statins from 1 August 1997 to 31 March 2010. The analysis was restricted to new users who had not been prescribed a statin in at least the preceding year. Patients with established diabetes before the start of treatment were excluded. Interventions Treatment with statins. Main outcome measure Incident diabetes. Results Compared with pravastatin (the reference drug in all analyses), there was an increased risk of incident diabetes with atorvastatin (adjusted hazard ratio 1.22, 95% confidence interval 1.15 to 1.29), rosuvastatin (1.18, 1.10 to 1.26), and simvastatin (1.10, 1.04 to 1.17). There was no significantly increased risk among people who received fluvastatin (0.95, 0.81 to 1.11) or lovastatin (0.99, 0.86 to 1.14). The absolute risk for incident diabetes was about 31 and 34 events per 1000 person years for atorvastatin and rosuvastatin, respectively. There was a slightly lower absolute risk with simvastatin (26 outcomes per 1000 person years) compared with pravastatin (23 outcomes per 1000 person years). Our findings were consistent regardless of whether statins were used for primary or secondary prevention of cardiovascular disease. Although similar results were observed when statins were grouped by potency, the risk of incident diabetes associated with use of rosuvastatin became non-significant (adjusted hazard ratio 1.01, 0.94 to 1.09) when dose was taken into account. Conclusions Compared with pravastatin, treatment with higher potency statins, especially atorvastatin and simvastatin, might be associated with an increased risk of new onset diabetes.

Adherence to Multiple Sclerosis Disease-Modifying Therapies in Ontario is Low

BACKGROUND/OBJECTIVE Differences in patient adherence to various disease-modifying drugs (DMDs) in the treatment of multiple sclerosis (MS) are not well understood. The goal of this study was to evaluate adherence of adult MS patients in Ontario with public drug plan coverage to various DMDs: intramuscular interferon beta-1a (i.m. IFNβ-1a, Avonex), subcutaneous interferon beta-1a (s.c. IFNβ-1a, Rebif), subcutaneous interferon beta-1b (IFNβ-1b, Betaseron) or glatiramer acetate (Copaxone). METHODS In this retrospective cohort study, Ontario Public Drug Plan beneficiaries aged 15 or older who were newly treated with i.m. IFNβ-1a, s.c. IFNβ-1a, IFNβ-1b or glatiramer acetate between April 2006 and March 2008 were followed forward until treatment discontinuation, switch to another DMD or a maximum two year follow-up period. Cumulative persistence rates were analyzed by the Kaplan-Meier method. The proportion of patients reaching the study endpoints after the two year follow-up period was also calculated. RESULTS Cumulative persistence rates for all four DMDs were similar over time (p=0.80), ranging from 73.6-79.1% at six months, 59.1-63.1% at one year and 41.5-47.4% at two years. After two years, the proportion of patients who had discontinued treatment, switched to another DMD or died was similar among DMDs (p=0.79, Fishers exact test). Switching between DMD types was low and occurred in 3.4-6.5% of new DMD users. CONCLUSIONS Adherence to DMDs in adult MS patients in Ontario is poor, which is consistent with previously reported adherence rates to MS DMDs in other regions. No significant differences in adherence exist between the DMDs evaluated in this study.

Triptans in the acute treatment of migraine: A systematic review and network meta-analysis.

Although triptans are widely used in the acute management of migraine, there is uncertainty around the comparative efficacy of triptans among each other and vs non‐triptan migraine treatments. We conducted systematic reviews and network meta‐analyses to compare the relative efficacy of triptans (alone or in combination with other drugs) for acute treatment of migraines compared with other triptan agents, non‐steroidal anti‐inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA), acetaminophen, ergots, opioids, or anti‐emetics.

No Increase in Adverse Events During Aliskiren Use Among Ontario Patients Receiving Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers

BACKGROUND Some evidence suggests that the direct renin inhibitor aliskiren may increase the risk of severe hyperkalemia, stroke, or acute kidney injury (AKI) when prescribed with angiotensin-converting enzyme inhibitors (ACEis) or angiotensin-receptor blockers (ARBs). The extent to which concomitant treatment increases the risk of these outcomes in routine clinical practice is unknown. We addressed this issue with the use of administrative databases. METHODS We established a cohort of Ontarians treated with an ACEi or an ARB. Within this cohort, we conducted 3 case-control studies. Cases were patients hospitalized with 1 of 3 outcomes (hyperkalemia, AKI, or stroke). In each analysis, we identified up to 5 matched control subjects for each case. Conditional logistic regression was used to examine the association between hospitalization for each outcome and the use of aliskiren in the preceding 60 days. RESULTS Among 903,346 patients aged 66 years and older treated with an ACEi or ARB during the 28-month study period, we identified 4235 hospitalized with hyperkalemia, 18,231 hospitalized with AKI, and 8283 hospitalized with stroke. After extensive multivariable adjustment, aliskiren therapy was not associated with a significant increase in the risk of hospitalization for hyperkalemia, AKI, or stroke. We found similar results in stratified analyses of patients with and without a history of chronic kidney disease, diabetes, or heart failure. CONCLUSIONS Among community-dwelling patients aged 66 years and older receiving therapy with an ACEi or an ARB, aliskiren use was not associated with hospitalization for hyperkalemia, AKI, or stroke.

The Burden of Opioid-Related Mortality in the United States

Key Points Question What has been the burden of opioid-related deaths in the United States over a recent 15-year period? Findings In this serial cross-sectional study, we found that the percentage of all deaths attributable to opioids increased 292% (from 0.4% to 1.5%) between 2001 and 2016, resulting in approximately 1.68 million person-years of life lost in 2016 alone (5.2 per 1000 population). The burden was particularly high among adults aged 24 to 35 years; in 2016, 20% of deaths in this age group involved opioids. Meaning Premature death from opioids imposes an enormous and growing public health burden across the United States.

Novel Oral Anticoagulants and the Risk of Major Hemorrhage in Elderly Patients With Chronic Kidney Disease: A Nested Case-Control Study

BACKGROUND The novel oral anticoagulants, including dabigatran and rivaroxaban, differ in their degree of renal excretion. METHODS We conducted a population-based nested case-control study in patients 66 years and older with chronic kidney disease (CKD) (excluding patients undergoing chronic dialysis) who received an oral anticoagulant between April 2006 and March 2013. We calculated odds ratios for hospitalization with a major hemorrhagic event and receipt of dabigatran, rivaroxaban, or warfarin in the preceding 60 days. We also performed a sensitivity analysis to investigate whether a relationship exists between major hemorrhage and advanced age (age < 80 years or ≥ 80 years). RESULTS We identified 237,409 patients with CKD, 4470 (1.9%) of whom experienced a major hemorrhage. We matched these patients to 14,460 controls. The use of dabigatran or rivaroxaban was not associated with a statistically significant elevated risk of hemorrhage compared with warfarin (adjusted odds ratio [aOR], 1.15; 95% confidence interval [CI], 0.91-1.45 for dabigatran; aOR, 1.22; 95% CI, 0.83-1.79 for rivaroxaban). Our sensitivity analysis found that older age was associated with an increased risk of hemorrhage for patients receiving dabigatran (aOR, 1.41; 95% CI, 1.06-1.88); results were similar but did not reach statistical significance for rivaroxaban (aOR, 1.57; 95% CI, 0.91-2.69). CONCLUSIONS Among elderly patients with CKD, exposure to dabigatran or rivaroxaban was not associated with a statistically significant increased risk of major hemorrhagic events compared with exposure to warfarin.

Allergen immunotherapy for the treatment of allergic rhinitis and/or asthma: an umbrella review

BACKGROUND Allergic rhinitis and asthma are important public health concerns, yet there is no consensus about the benefits and harms of allergen-specific immunotherapy to treat these conditions. We performed an umbrella review of systematic reviews summarizing the current evidence for the benefits and harms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). METHODS We searched MEDLINE, Embase, the Cochrane Library and the grey literature from Jan. 1, 2010 to Nov. 20, 2016 for systematic reviews of randomized controlled trials or prospectively controlled studies involving children or adults with allergic rhinitis or asthma. Outcomes were summarized narratively (benefits: total combined symptom-medication score, symptom score, medication score, disease-specific quality of life, adherence; harms: anaphylaxis, death, local and systemic reactions). RESULTS Twenty-three systematic reviews were included. SCIT and SLIT were more effective than placebo for most outcomes. SCIT was better than SLIT at improving medication and symptom scores, with no differences in quality of life; however, data were limited for this comparison. Anaphylaxis and death were infrequently reported. Few reviews assessed benefits or harms among children. INTERPRETATION Allergen immunotherapy appears to be effective among patients with allergic rhinitis and asthma. The safety of allergen immunotherapy is not conclusively established, although death and anaphylaxis appear to be rare. PROSPERO no.: CRD42015024590.

Trends in the use and cost of antipsychotics among older adults from 2007 to 2013: a repeated cross-sectional study

BACKGROUND Recently, several new atypical antipsychotic agents have been introduced in Ontario, and regulatory warnings have been issued regarding use of atypical antipsychotics in older adults. We sought to establish the impact of newer atypical antipsychotics on prescribing rates and costs. METHODS We performed a population-based cross-sectional study of Ontario adults aged 65 years or more using atypical antipsychotics from Jan. 1, 2007, to Mar. 31, 2013. These people have universal access to publicly funded drugs through the Ontario Health Insurance Plan and the Ontario Drug Benefit. We conducted time-series analysis to assess the impact of the introduction of new atypical antipsychotics on rates of use of atypical antipsychotics and associated expenditures. RESULTS Rates of atypical antipsychotic use increased following the introduction of new agents in 2009, from 27.6 users per 1000 older adults in the third quarter of 2009 to 29.1 users per 1000 older adults at the end of the study period (p = 0.04). Although prescribing rates for the newer atypical agents (paliperidone, ziprasidone and aripiprazole) remained low relative to their older counterparts (risperidone, olanzapine and quetiapine), rates of aripiprazole use rose to 1.0 user per 1000 older adults by the end of the study period. The proportion of prescriptions that were for brand-name agents fell from 57.5% in the second quarter of 2007 to 6.1% in the second quarter of 2009, and then rose to 11.7% by the end of the study period. By the first quarter of 2013, newer atypical antipsychotic agents were used by 4.4% of atypical antipsychotic users but accounted for 14.1% (

Publicly funded overactive bladder drug treatment patterns in Ontario over 15 years: An ecological study

1.2 million of

Factors that may be influencing the rise in prescription testosterone replacement therapy in adult men: a qualitative study

8.5 million) of atypical antipsychotic expenditures. INTERPRETATION Although the overall prevalence of use of new atypical antipsychotic agents remains low, their introduction has led to increased prescribing of this class of drugs in older adults. Given the potential cost implications, further study of these trends would be prudent.