Colette Raymond

Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases

Objective To quantify an association between acute kidney injury and use of high potency statins versus low potency statins. Design Retrospective observational analysis of administrative databases, using nine population based cohort studies and meta-analysis. We performed as treated analyses in each database with a nested case-control design. Rate ratios for different durations of current and past statin exposure to high potency or low potency statins were estimated using conditional logistic regression. Ratios were adjusted for confounding by high dimensional propensity scores. Meta-analytic methods estimated overall effects across participating sites. Setting Seven Canadian provinces and two databases in the United Kingdom and the United States. Participants 2 067 639 patients aged 40 years or older and newly treated with statins between 1 January 1997 and 30 April 2008. Each person hospitalized for acute kidney injury was matched with ten controls. Intervention A dispensing event was new if no cholesterol lowering drug or niacin prescription was dispensed in the previous year. High potency statin treatment was defined as ≥10 mg rosuvastatin, ≥20 mg atorvastatin, and ≥40 mg simvastatin; all other statin treatments were defined as low potency. Statin potency groups were further divided into cohorts with or without chronic kidney disease. Main outcome measure Relative hospitalization rates for acute kidney injury. Results Of more than two million statin users (2 008 003 with non-chronic kidney disease; 59 636 with chronic kidney disease), patients with similar propensity scores were comparable on measured characteristics. Within 120 days of current treatment, there were 4691 hospitalizations for acute kidney injury in patients with non-chronic kidney injury, and 1896 hospitalizations in those with chronic kidney injury. In patients with non-chronic kidney disease, current users of high potency statins were 34% more likely to be hospitalized with acute kidney injury within 120 days after starting treatment (fixed effect rate ratio 1.34, 95% confidence interval 1.25 to 1.43). Users of high potency statins with chronic kidney disease did not have as large an increase in admission rate (1.10, 0.99 to 1.23). χ2 tests for heterogeneity confirmed that the observed association was robust across participating sites. Conclusions Use of high potency statins is associated with an increased rate of diagnosis for acute kidney injury in hospital admissions compared with low potency statins. The effect seems to be strongest in the first 120 days after initiation of statin treatment.

Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases

Objective To evaluate the incremental increase in new onset diabetes from higher potency statins compared with lower potency statins when used for secondary prevention. Design Eight population based cohort studies and a meta-analysis. Setting Six Canadian provinces and two international databases from the UK and US. Participants 136 966 patients aged ≥40 years newly treated with statins between 1 January 1997 and 31 March 2011. Methods Within each cohort of patients newly prescribed a statin after hospitalisation for a major cardiovascular event or procedure, we performed as-treated, nested case-control analyses to compare diabetes incidence in users of higher potency statins with incidence in users of lower potency statins. Rate ratios of new diabetes events were estimated using conditional logistic regression on different lengths of exposure to higher potency versus lower potency statins; adjustment for confounding was achieved using high dimensional propensity scores. Meta-analytic methods were used to estimate overall effects across sites. Main outcome measures Hospitalisation for new onset diabetes, or a prescription for insulin or an oral antidiabetic drug. Results In the first two years of regular statin use, we observed a significant increase in the risk of new onset diabetes with higher potency statins compared with lower potency agents (rate ratio 1.15, 95% confidence interval 1.05 to 1.26). The risk increase seemed to be highest in the first four months of use (rate ratio 1.26, 1.07 to 1.47). Conclusions Higher potency statin use is associated with a moderate increase in the risk of new onset diabetes compared with lower potency statins in patients treated for secondary prevention of cardiovascular disease. Clinicians should consider this risk when prescribing higher potency statins in secondary prevention patients.

Characterizing early prescribers of newly marketed drugs in Canada: a population-based study

BackgroundThe diffusion of innovations model proposes that early adopters of innovation influence others. This study was undertaken to determine if early prescribers and users of newly marketed drugs had different sociodemographic and professional characteristics as compared to majority and late users and prescribers.MethodsAfter market availability in Manitoba, Canada, of celecoxib, alendronate, clopiodogrel and pantoprazole, time to first prescriptions was determined. Early, majority and late adopters of the new drug were characterized by this diffusion time. The prescription, health and prescriber records were compared across adopter categories. The likelihood of being an early or late prescriber or user of the new medications according to patient demographic characteristics, physician factors (specialty and place of training) and neighborhood income was determined with polytomous logistic regression.ResultsCelecoxib demonstrated a much more rapid uptake into routine use than the other drugs. More than 300 Manitoba physicians prescribed celecoxib within two weeks of market availability. Early prescribers of celecoxib were more likely than majority prescribers to be general practitioners (OR = 1.81, 95%CI: 1.40–2.35) and have hospital affiliations (OR = 1.35, 95%CI: 1.03–1.77). Early users of celecoxib were more likely than the majority to have arthritic conditions, have a high income and have paid out-of-pocket for their prescription. For alendronate, clopidogrel and pantoprazole, only prescription drug coverage predicted adopter category. Early prescribers of one new drug were not early prescribers of the other new drugs.ConclusionNo common group of patients or physicians who were early prescribers or users of all four medications was described.

Proton Pump Inhibitors and the Risk of Adverse Cardiac Events

Background Recent evidence suggests that proton pump inhibitors (PPIs) might be linked with adverse cardiac events, but a causal relationship is unproven. Methods We applied the self-matched case series method to two studies using population-based health care data from Ontario, Canada between 1996 and 2008. The first included subjects aged 66 years or older hospitalized for acute myocardial infarction within 12 weeks following initiation of PPI, while the second included subjects hospitalized for heart failure. In both studies we designated the primary risk interval as the initial 4 weeks of therapy and the control interval as the final 4 weeks. To test the specificity of our findings we examined use of histamine H2 receptor antagonists and benzodiazepines, drugs with no plausible causal link to adverse cardiac events. Results During the 13-year study period, we identified 5550 hospital admissions for acute myocardial infarction and 6003 admissions for heart failure within 12 weeks of commencing PPI therapy. In the main analyses, we found that initiation of a PPI was associated with a higher risk of acute myocardial infarction (odds ratio 1.8; 95% confidence interval 1.7 to 1.9) and heart failure (odds ratio 1.8; 95% confidence interval 1.7 to 1.9). However, secondary analyses revealed similar risk estimates histamine H2 receptor antagonists and benzodiazepines, drugs with no known or suspected association with adverse cardiac events. Conclusion PPIs are associated with a short-term risk of adverse cardiac events, but similar associations are seen with other drugs exhibiting no known cardiac toxicity. Collectively these observations suggest that the association between PPIs and adverse cardiac events does not represent reflect cause-and-effect.

Prescribing of psychotropic medications to the elderly population of a Canadian province: a retrospective study using administrative databases

Background. Psychotropic medications, in particular second-generation antipsychotics (SGAs) and benzodiazepines, have been associated with harm in elderly populations. Health agencies around the world have issued warnings about the risks of prescribing such medications to frail individuals affected by dementia and current guidelines recommend their use only in cases where the benefits clearly outweigh the risks. This study documents the use of psychotropic medications in the entire elderly population of a Canadian province in the context of current clinical guidelines for the treatment of behavioural disturbances. Methods. Prevalent and incident utilization of antipsychotics, benzodiazepines and related medications (zopiclone and zaleplon) were determined in the population of Manitobans over age 65 in the time period 1997/98 to 2008/09 fiscal years. Comparisons between patients living in the community and those living in personal care (nursing) homes (PCH) were conducted. Influence of sociodemographic characteristics on prescribing was assessed by generalized estimating equations. Non-optimal use was defined as the prescribing of high dose of antipsychotic medications and the use of combination therapy of a benzodiazepine (or zopiclone/zaleplon) with an antipsychotic. A decrease in intensity of use over time and lower proportions of patients treated with antipsychotics at high dose or in combination with benzodiazepines (or zopiclone/zaleplon) was considered a trend toward better prescribing. Multiple regression analysis determined predictors of non-optimal use in the elderly population. Results. A 20-fold greater prevalent utilization of SGAs was observed in PCH-dwelling elderly persons compared to those living in the community. In 2008/09, 27% of PCH-dwelling individuals received a prescription for an SGA. Patient characteristics, such as younger age, male gender, diagnoses of dementia (or use of an acetylcholinesterase inhibitor) or psychosis in the year prior the prescription, were predictors of non-optimal prescribing (e.g., high dose antipsychotics). During the period 2002/3 and 2007/8, amongst new users of SGAs, 10.2% received high doses. Those receiving high dose antipsychotics did not show high levels of polypharmacy. Conclusions. Despite encouraging trends, the use of psychotropic medications remains high in elderly individuals, especially in residents of nursing homes. Clinicians caring for such patients need to carefully assess risks and benefits.

Proportion of opioid use due to compensated workers' compensation claims in Manitoba, Canada.

Background This study identifies the percentage of opioids prescribed for compensated workplace conditions in Manitoba, Canada and whether Workers Compensation Board (WCB) status is associated with higher prescription opioid doses. Methods Opioid prescriptions for WCB recipients were linked with databases housed at the Manitoba Center for Health Policy. Duration of continuous opioid prescription and morphine equivalents (ME) per day (ME/D) were calculated for individuals age 18–65. Results Over the period from 1998 to 2010, 3.8% of the total opioid dosage of medication prescribed in the study population were prescribed to WCB recipients. WCB recipients accounted for 2.1% of the individuals prescribed opioids. In adjusted analyses WCB recipients were more likely to be prescribed over 120 ME/D (OR 2.06 95% CI, 1.58–2.69). Conclusions WCB recipients account for a small, but significant amount of the total opioid prescribed in Manitoba. Manitobas WCB population is a group at increased risk of being prescribed over 120 ME/day. Am. J. Ind. Med. 58:33–39, 2015.

Psychotropic Drug Use before, during, and after Pregnancy: A Population-Based Study in a Canadian Cohort (2001-2013):

Objective: To describe the extent of increase in use and the rate of continuation versus discontinuation of psychotropic agents before, during, and after pregnancy. Methods: Rates of psychotropic use (antidepressants, anxiolytic/sedative-hypnotics, antiepileptics, antipsychotics, lithium, stimulants) among women with a hospital-recorded pregnancy outcome were assessed using databases at the Manitoba Centre for Health Policy. Rate of use was defined as ≥1 prescription over the total number of pregnancies in the 3-12 months before pregnancy, 0-3 months before pregnancy, during pregnancy, or 3 months after pregnancy. Continued use was defined as ≥2 prescriptions with gap ≤14 days. Poisson regression was used to analyze trends. Results: Over the study period, a psychotropic drug was used before, during, or after pregnancy in 41,923 of 224,762 pregnancies. From 2001 to 2013, psychotropic use increased 1.5-fold from 11.1% to 16.2% (p < 0.0001) in the 3-12 months before pregnancy, 1.6-fold from 6.4% to 10.5% (p < 0.0001) in the 3 months before pregnancy, 1.8-fold from 3.3% to 6.0% (p < 0.0001) during pregnancy, and 1.5-fold from 6.2% to 9.5% (p < 0.0001) in the 3 months postpartum. Among the 13,579 women who received at least 1 psychotropic agent in the 3 months prior to pregnancy, 38.5% stopped the agent prior to pregnancy and only 10.3% continued use throughout pregnancy. Continued use throughout pregnancy was higher (56.9%) among the 6693 women who received at least 2 prescriptions for a psychotropic agent and were at least 80% adherent in the 3 months prior to pregnancy. Conclusion: The use of psychotropic agents increased over 12 years. The safety of continuing versus discontinuing these agents during pregnancy remains uncertain, but we observed a decrease in psychotropic drug use during the pregnancy period.

The impact of opioid prescription dose and duration during a Workers Compensation claim, on post‐claim continued opioid use: A retrospective population‐based study

BACKGROUND Workers Compensation Board (WCB) recipients are a group commonly prescribed opioids. METHODS We explored factors influencing post-claim opioid dose and duration by linking data from 22,451 claims with the Manitoba Center for Population Health registry. RESULTS On average, the WCB paid for 94.55% of opioids prescribed during a claim. The amount paid for by the WCB varied significantly by total opioids prescribed. The main predictors of high opioid dosage (120 + morphine equivalents (ME)/day) during the first year post-claim (logistic regression), and of longer post-claim opioid usage (survival analysis), included opioid dosage during the final month of the claim both paid for and not paid for by the WCB. CONCLUSIONS Amongst low dose opioid claims, the WCB covers most opioids prescribed. Higher opioid dose WCB recipients are often prescribed opioids not covered by the WCB. Both opioids paid for and not paid for by the WCB are associated with post-claim opioid use.

The role of hematopoietic cell transplantation in adult ALL: clinical equipoise persists.

Adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1) may be treated either with ongoing systemic chemotherapy or with allogeneic hematopoietic cell transplantation (alloHCT). Despite the presence of phase III trials to support clinical decision-making, we hypothesized that physicians who treat adult ALL would demonstrate wide practice variation. Canadian hematologists who treat ALL were surveyed electronically. Overall, 69 of 173 physicians responded (40%). There was high agreement with offering alloHCT for ALL with high-risk cytogenetics or induction failure after a single chemotherapy cycle. However, only a minority of respondents felt that age >35 years was an indication for alloHCT in CR1. Almost all respondents (96%) felt that a well-matched unrelated donor was an acceptable alternative to a sibling donor. There was uncertainty about the role of cord blood (53% agree) and the utility of reduced intensity conditioning HCT (41% agree). In contrast to the results of the MRC/ECOG study, respondents considered alloHCT to be particularly helpful in high-risk patients. Consensus was lacking on the use of cord blood, RIC alloHCT, and the application of MRD. Equipoise exists on the role of alloHCT in CR1 in ALL, suggesting that further trials in this area are required.

Role of the pharmacist in a presurgical clinic designed to optimize outcomes after elective total joint arthroplasty

It is well documented that clinical pharmacists who provide pharmaceutical care reduce the frequency of drug-related problems (DRPs) and that optimization of drug therapy in this way may influence health expenses, patients’ quality of life, and mortality rates.[1][1],[2][2] It is common for