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Background: Muscular dystrophies (MDs) are characterized by chronic muscle wasting but also poorly understood metabolic co-morbidities. We have recently shown that Duchenne MD (DMD) patients, dogs and asymptomatic carriers are affected by a new form of dyslipidemia that may exacerbate muscle damage.Objective: We aimed to perform a systematic review and meta-analysis for evidence that other types of MDs are associated with dyslipidemia compared to healthy controls.Methods: Search was conducted using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials for reports that compare plasma/serum lipids from MD patients and controls, and meta-analysis of cross-sectional studies quantifying total cholesterol, high-density lipoprotein, low density lipoprotein and triglycerides was performed.Results: Out of 749 studies, 17 met our inclusion criteria for meta-analysis. 14 of the 17 studies (82%) included investigated myotonic dystrophy (DM); other studies were on pseudohypertrophic MD (PMD) or DMD. As a whole, MD individuals had significantly higher levels of circulating total cholesterol (Hedges’ g with 95% confidence interval [CI], 0.80 [0.03 – 1.56]; p?=?0.04) and triglycerides (Hedges’ g with 95% confidence interval [CI], 2.28[0.63 – 3.92]; p?=?0.01) compared to controls. Meta-regression analysis showed the percentage of male gender was significantly associated with the difference in total cholesterol (beta?=?0.05; 95% CI, – 0.02 to 0.11; p?=?0.043) and high-density lipoprotein (beta?=?– 9.38; 95% CI, – 16.26 to – 2.50; p?=?0.028).Conclusions: MD is associated with significantly higher circulating levels of total cholesterol and triglycerides. However, caution on the interpretation of these findings is warranted and future longitudinal research is required to better understand this relationship.

Muscular dystrophies (MDs) are characterized by chronic muscle wasting but also poorly understood metabolic co-morbidities. We have recently shown that Duchenne MD (DMD) patients, dogs and asymptomatic carriers are affected by a new form of dyslipidemia that may exacerbate muscle damage. We aimed to perform a systematic review and meta-analysis for evidence that other types of MDs are associated with dyslipidemia compared to healthy controls. Search was conducted using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials for reports that compare plasma/serum lipids from MD patients and controls, and meta-analysis of cross-sectional studies quantifying total cholesterol, high-density lipoprotein, low density lipoprotein and triglycerides was performed. Out of 749 studies, 17 met our inclusion criteria for meta-analysis. 14 of the 17 studies (82%) included investigated myotonic dystrophy (DM); other studies were on pseudohypertrophic MD (PMD) or DMD. As a whole, MD individuals had significantly higher levels of circulating total cholesterol (Hedges’ g with 95% confidence interval [CI], 0.80 [0.03 – 1.56]; p = 0.04) and triglycerides (Hedges’ g with 95% confidence interval [CI], 2.28[0.63 – 3.92]; p = 0.01) compared to controls. Meta-regression analysis showed the percentage of male gender was significantly associated with the difference in total cholesterol (beta = 0.05; 95% CI, – 0.02 to 0.11; p = 0.043) and high-density lipoprotein (beta = – 9.38; 95% CI, – 16.26 to – 2.50; p = 0.028). MD is associated with significantly higher circulating levels of total cholesterol and triglycerides. However, caution on the interpretation of these findings is warranted and future longitudinal research is required to better understand this relationship.

ABSTRACTIntroductionMany adverse effects of medicines only become known after approval, prompting regulatory agencies to issue post-market safety advisories to support safer care. Our team evaluated advisories issued by national regulators in Australia, Canada, Denmark, the United Kingdom, and the United States from 2007 to 2016 inclusive, comparing regulators’ decisions to warn, effects on prescribing, doctors’ awareness and responses to warnings, relevant regulatory policies, and specific case studies.Areas CoveredBased mainly on our research program and a narrative review, this commentary describes how often regulators issue safety advisories and effects on clinical practice. We found extensive differences in decisions to warn, timing and content of warnings. Monitoring advice is often inadequate. The most systematic estimate suggests an average reduction in prescribing of around 6% compared with settings with no advisory. Interviews with doctors suggest limited awareness, uptake, and at times belief in these warnings.Expert OpinionPost-market safety advisories are an important intervention aiming to improve prescribing and use of medicines. However, differing warnings mean that some patients may be exposed to riskier prescribing than others. Better integration of safety information into clinical practice is needed, as well as improved transparency, independence, and public engagement in regulatory decision-making.

Objective.To compare medication persistence of tofacitinib with persistence of injectable biological disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA).Methods.We performed a retrospective new-user cohort study of patients with RA in the IBM MarketScan Research Databases. New users of tofacitinib or bDMARD were identified between November 2012 and December 2016. Persistence, in number of years, was the time between treatment initiation and the earliest occurrence of discontinuation or switching from the medication prescribed at cohort entry. Persistence of tofacitinib was compared with bDMARD persistence using Cox proportional hazards regression with adjustment for high-dimensional propensity scores. Similar methods were used for an analysis of post first-line therapy in patients who switched to tofacitinib from a bDMARD.Results.New tofacitinib users (n = 1031) were 56 years of age, on average, and 82% were women. New bDMARD users (n = 17,803) were 53 years of age, on average, and 78% were women. New tofacitinib users had shorter medication persistence (median 0.81 yrs) compared to bDMARD patients (1.02 yrs). After adjustment, the HR for discontinuation of tofacitinib compared with bDMARD was 1.14 (95% CI 1.05–1.25). Patients who switched to tofacitinib from a bDMARD had longer persistence than patients who switched to a bDMARD (adjusted HR for discontinuation 0.90, 95% CI 0.83–0.97).Conclusion.Further research is warranted to understand the reasons for discontinuation of tofacitinib despite its ease of administration and to understand the observed differences between switchers and new users.

IMPORTANCE: The association between incretin-based drugs, such as dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, and acute pancreatitis is controversial. OBJECTIVE: To determine whether the use of incretin-based drugs, compared with the use of 2 or more other oral antidiabetic drugs, is associated with an increased risk of acute pancreatitis. DESIGN, SETTING, AND PARTICIPANTS: A large, international, multicenter, population-based cohort study was conducted using combined health records from 7 participating sites in Canada, the United States, and the United Kingdom. An overall cohort of 1 532 513 patients with type 2 diabetes initiating the use of antidiabetic drugs between January 1, 2007, and June 30, 2013, was included, with follow-up until June 30, 2014. EXPOSURES: Current use of incretin-based drugs compared with current use of at least 2 oral antidiabetic drugs. MAIN OUTCOMES AND MEASURES: Nested case-control analyses were conducted including hospitalized patients with acute pancreatitis matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and follow-up duration. Hazard ratios (HRs) and 95% CIs for hospitalized acute pancreatitis were estimated and compared current use of incretin-based drugs with current use of 2 or more oral antidiabetic drugs. Secondary analyses were performed to assess whether the risk varied by class of drug (DPP-4 inhibitors and GLP-1 agonists) or by duration of use. Site-specific HRs were pooled using random-effects models. RESULTS: Of 1 532 513 patients included in the analysis, 781 567 (51.0%) were male; mean age was 56.6 years. During 3 464 659 person-years of follow-up, 5165 patients were hospitalized for acute pancreatitis (incidence rate, 1.49 per 1000 person-years). Compared with current use of 2 or more oral antidiabetic drugs, current use of incretin-based drugs was not associated with an increased risk of acute pancreatitis (pooled adjusted HR, 1.03; 95% CI, 0.87-1.22). Similarly, the risk did not vary by drug class (DPP-4 inhibitors: pooled adjusted HR, 1.09; 95% CI, 0.86-1.22; GLP-1 agonists: pooled adjusted HR, 1.04; 95% CI, 0.81-1.35) and there was no evidence of a duration-response association. CONCLUSIONS AND RELEVANCE: In this large population-based study, use of incretin-based drugs was not associated with an increased risk of acute pancreatitis compared with other oral antidiabetic drugs.

Cholinesterase inhibitors (ChEIs) are widely used to treat mild to moderate Alzheimer's disease and related dementia. Clinical trials have focused on placebo comparisons, inadequately addressing within-class comparative safety.

It has been anecdotally reported that nocturnal leg cramps in pregnant women are worse in summer. We analyzed population-level data to determine whether the symptom burden of nocturnal leg cramps is seasonal in the general population.

Background:Isotretinoin, a teratogen, is widely used to treat cystic acne. Although the risks of pregnancy during isotretinoin therapy are well recognized, there are doubts about the level of adherence with the pregnancy prevention program in Canada. Our objective was to evaluate the effectiveness of the Canadian pregnancy prevention program in 4 provinces: British Columbia, Saskatchewan, Manitoba and Ontario.Methods:Using administrative data, we identified 4 historical cohorts of female users of isotretinoin (aged 12–48 yr) for the period 1996 to 2011. We defined pregnancy using International Statistical Classification of Diseases and billing codes. One definition included only cases with documented pregnancy outcomes (high-specificity definition); the other definition also included individuals recorded as receiving prenatal care (high-sensitivity definition). We studied new courses of isotretinoin and detected pregnancies in 2 time windows: during isotretinoin treatment only and up to 42 weeks after treatment. Live births were followed for 1 year to identify congenital malformations.Results:A total of 59 271 female patients received 102 308 courses of isotretinoin. Between 24.3% and 32.9% of participants received prescriptions for oral contraceptives while they were taking isotretinoin, compared with 28.3% to 35.9% in the 12 months before isotretinoin was started. According to the high-specificity definition of pregnancy, there were 186 pregnancies during isotretinoin treatment (3.1/1000 isotretinoin users), compared with 367 (6.2/1000 users) according to the high-sensitivity definition. By 42 weeks after treatment, there were 1473 pregnancies (24.9/1000 users), according to the high-specificity definition. Of these, 1331 (90.4%) terminated spontaneously or were terminated by medical intervention. Among the 118 live births were 11 (9.3%) cases of congenital malformation. Pregnancy rates during isotretinoin treatment remained constant between 1996 and 2011.Interpretation:Adherence to the isotretinoin pregnancy prevention program in Canada was poor during the 15-year period of this study.

Background:Opioid analgesics and benzodiazepines are often misused in clinical practice. We determined whether implementation of a centralized prescription network offering real-time access to patient-level data on filled prescriptions (PharmaNet) reduced the number of potentially inappropriate prescriptions for opioids and benzodiazepines.Methods:We conducted a time series analysis using prescription records between Jan. 1, 1993, and Dec. 31, 1997, for residents of the province of British Columbia who were receiving social assistance or were 65 years or older. We calculated monthly percentages of filled prescriptions for an opioid or a benzodiazepine that were deemed inappropriate (those issued by a different physician and dispensed at a different pharmacy within 7 days after a filled prescription of at least 30 tablets of the same drug).Results:Within 6 months after implementation of PharmaNet in July 1995, we observed a relative reduction in inappropriate filled prescriptions for opioids of 32.8% (95% confidence interval [CI] 31.0%–34.7%) among patients receiving social assistance; inappropriate filled prescriptions for benzodiazepines decreased by 48.6% (95% CI 43.2%–53.1%). Similar and statistically significant reductions were observed among residents 65 years or older.Interpretation:The implementation of a centralized prescription network was associated with a dramatic reduction in inappropriate filled prescriptions for opioids and benzodiazepines.

BACKGROUND: The annual cut-off date of birth for entry to school in British Columbia, Canada, is Dec. 31. Thus, children born in December are typically the youngest in their grade. We sought to determine the influence of relative age within a grade on the diagnosis and pharmacologic treatment of attention-deficit/hyperactivity disorder (ADHD) in children. METHODS: We conducted a cohort study involving 937 943 children in British Columbia who were 6–12 years of age at any time between Dec. 1, 1997, and Nov. 30, 2008. We calculated the absolute and relative risk of receiving a diagnosis of ADHD and of receiving a prescription for a medication used to treat ADHD (i.e., methylphenidate, dextroamphetamine, mixed amphetamine salts or atomoxetine) for children born in December compared with children born in January. RESULTS: Boys who were born in December were 30% more likely (relative risk [RR] 1.30, 95% confidence interval [CI] 1.23–1.37) to receive a diagnosis of ADHD than boys born in January. Girls born in December were 70% more likely (RR 1.70, 95% CI 1.53–1.88) to receive a diagnosis of ADHD than girls born in January. Similarly, boys were 41% more likely (RR 1.41, 95% CI 1.33–1.50) and girls 77% more likely (RR 1.77, 95% CI 1.57–2.00) to be given a prescription for a medication to treat ADHD if they were born in December than if they were born in January. INTERPRETATION: The results of our analyses show a relative-age effect in the diagnosis and treatment of ADHD in children aged 6–12 years in British Columbia. These findings raise concerns about the potential harms of overdiagnosis and overprescribing. These harms include adverse effects on sleep, appetite and growth, in addition to increased risk of cardiovascular events.

Health plans that increase prescription cost-sharing for their patients may increase overall plan costs. We analyzed the impact on health plan spending of a switch in public drug insurance from full coverage to a prescription copayment (copay), and then to income-based deductibles plus coinsurance (IBD).

Reference drug pricing (RP) is a cost-sharing strategy commonly used to control drug expenditures. Under RP, a benefit plan fully reimburses medications that are equally or less expensive than the reference price, and requires patients to pay the extra cost of therapeutically equivalent but higher priced drugs. Critics argued that drug plan savings are offset by administrative costs and increased spending on other health services.

Objective: Reference pricing is a medication cost-sharing policy that fully covers medications which are less expensive than a standard reference price and requires patients to pay the extra cost of higher-priced drugs in a class of therapeutically substitutable drugs. Little information exists on the clinical and economic consequences. We analyzed changes in drug utilization, physician visits, hospitalizations, long-term care admissions, and expenditures after the introduction of reference pricing for dihydropyridine calcium channel blockers (CCBs) among patients aged 65 years or older in British Columbia, Canada.Methods: This quasiexperimental longitudinal study was performed in the setting of Pharmacare, the state-funded drug benefits plan of all elderly persons in British Columbia. Study patients comprised all elderly residents of British Columbia who were enrolled in the provincial health insurance program and received dihydropyridine CCBs at the time of the policy change (35,886) and a subgroup of high-priced dihydropyridine CCB users (23,116). We studied the implementation of reference drug pricing on Jan 1, 1997, affecting all elderly Pharmacare beneficiaries. The main outcome measures were drug utilization, drug expenditures, physician visits, hospitalizations, long-term care, and net savings.Results: The start of reference pricing was followed by a significant reduction in high-priced dihydropyridine CCBs (−150 monthly doses per 10,000 elderly persons), with a corresponding increase in fully covered dihydropyridine CCBs (+116). Overall, antihypertensive use did not decline (P = .46). Low-income status was a risk factor for discontinuing treatment (odds ratio, 1.64; 95% confidence interval [CI], 1.36 to 1.99); however, this was already observed to a similar magnitude 12 months before reference pricing (odds ratio, 1.46). In the overall study cohort, there was no increase in rates of physician visits, hospitalizations, and long-term care admissions. However, the 9% of patients who actually switched medications showed an 18% increase (95% CI, 8% to 28%) in physician visits and an increase of Canadian $13 (95% CI, Canadian $3 to Canadian $24) in costs of physician visits per patient as compared with nonswitchers during the transition but not afterward. This temporary increase may have been a result of additional prescribing and monitoring in switchers. Changes in drug expenditures and physician services resulted in net savings of Canadian $1.6 million in the first 12 months of policy implementation.Conclusions: Reference pricing as implemented in British Columbia may be a model for successful pharmaceutical cost-containment without adversely affecting patients or cost-shifting.

IMPORTANCE: Ondansetron is frequently used to treat nausea and vomiting during pregnancy. Although some studies reported important safety signals, few studies have been sufficiently large to assess rare pregnancy outcomes. OBJECTIVE: To study the association between ondansetron exposure during pregnancy and the risks of spontaneous abortion, stillbirth, and major congenital malformations. DESIGN, SETTING, AND PARTICIPANTS: This is a cohort study conducted in 3 countries, with a meta-analysis. Participants included women and girls aged 12 to 55 years who experienced spontaneous abortion, induced abortion, stillbirth, or live birth between April 2002 and March 2016, as recorded in administrative data from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, and Ontario), the US IBM MarketScan Research Databases, and the UK Clinical Practice Research Datalink. The statistical analysis was completed in October 2020. EXPOSURES: Exposure to ondansetron during pregnancy was compared with exposure to other commonly used antiemetics to minimize confounding by indication. MAIN OUTCOMES AND MEASURES: The primary outcome was fetal death, defined as either spontaneous abortion or stillbirth. Secondary outcomes were the 2 components of the primary outcome and major congenital malformations identified during the year after a live birth. Adjusted hazard ratios were estimated using Cox proportional hazards models with time-dependent drug exposures and were adjusted using high-dimensional propensity scores. For major congenital malformations, adjusted odds ratios were estimated from logistic models. Site-level results were pooled using random-effects meta-analysis. Sensitivity analyses considered second-line antiemetic exposure and exposure specifically during 4 to 10 weeks of gestation. RESULTS: Data from 456?963 pregnancies were included in this study of fetal death (249?787 [54.7%] in Canada, 197?913 [43.3%] in the US, and 9263 [2.0%] in the UK; maternal age, =24 years, 93?201 patients [20.4%]; 25-29 years, 149?117 patients [32.6%]; 30-34 years, 142?442 patients [31.2%]; and =35 years, 72?203 patients [15.8%]). Fetal death occurred in 12?907 (7.9%) of 163?810 pregnancies exposed to ondansetron, and 17?476 (5.7%) of 306?766 pregnancies exposed to other antiemetics. The adjusted hazard ratios were 0.91 (95% CI, 0.67-1.23) for fetal death with time-dependent ondansetron exposure during pregnancy, 0.82 (95% CI, 0.64-1.04) for spontaneous abortion, and 0.97 (95% CI, 0.79-1.20) for stillbirth. For major congenital malformations, the estimated odds ratio was 1.06 (95% CI, 0.91-1.22). Results of sensitivity analyses were generally consistent with those of the primary analyses. CONCLUSIONS AND RELEVANCE: In this large, multicenter cohort study, there was no association between ondansetron exposure during pregnancy and increased risk of fetal death, spontaneous abortion, stillbirth, or major congenital malformations compared with exposure to other antiemetic drugs.

ObjectiveTo compare the risk of cardiovascular events between sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors among people with type 2 diabetes in a real world context of clinical practice.DesignMulti-database retrospective cohort study using a prevalent new user design with subsequent meta-analysis.SettingCanadian Network for Observational Drug Effect Studies (CNODES), with administrative healthcare databases from seven Canadian provinces and the United Kingdom, 2013-18.Population209 867 new users of a SGLT2 inhibitor matched to 209 867 users of a DPP-4 inhibitor on time conditional propensity score and followed for a mean of 0.9 years.Main outcome measuresThe primary outcome was major adverse cardiovascular events (MACE, a composite of myocardial infarction, ischaemic stroke, or cardiovascular death). Secondary outcomes were the individual components of MACE, heart failure, and all cause mortality. Cox proportional hazards models were used to estimate site specific adjusted hazards ratios and 95% confidence intervals, comparing use of SGLT2 inhibitors with use of DPP-4 inhibitors in an as treated approach. Site specific results were pooled using random effects meta-analysis.ResultsCompared with DPP-4 inhibitors, SGLT2 inhibitors were associated with decreased risks of MACE (incidence rate per 1000 person years: 11.4 v16.5; hazard ratio 0.76, 95% confidence interval 0.69 to 0.84), myocardial infarction (5.1 v6.4; 0.82, 0.70 to 0.96), cardiovascular death (3.9 v7.7; 0.60, 0.54 to 0.67), heart failure (3.1 v7.7; 0.43, 0.37 to 0.51), and all cause mortality (8.7 v17.3; 0.60, 0.54 to 0.67). SGLT2 inhibitors had more modest benefits for ischaemic stroke (2.6 v3.5; 0.85, 0.72 to 1.01). Similar benefits for MACE were observed with canagliflozin (0.79, 0.66 to 0.94), dapagliflozin (0.73, 0.63 to 0.85), and empagliflozin (0.77, 0.68 to 0.87).ConclusionsIn this large observational study conducted in a real world clinical practice context, the short term use of SGLT2 inhibitors was associated with a decreased risk of cardiovascular events compared with the use of DPP-4 inhibitors.Trial registrationClinicalTrials.gov NCT03939624.

Objective To determine the safety of direct oral anticoagulant (DOAC) use compared with warfarin use for the treatment of venous thromboembolism.Design Retrospective matched cohort study conducted between 1 January 2009 and 31 March 2016.Setting Community based, using healthcare data from six jurisdictions in Canada and the United States.Participants 59 525 adults (12 489 DOAC users; 47 036 warfarin users) with a new diagnosis of venous thromboembolism and a prescription for a DOAC or warfarin within 30 days of diagnosis.Main outcome measures Outcomes included hospital admission or emergency department visit for major bleeding and all cause mortality within 90 days after starting treatment. Propensity score matching and shared frailty models were used to estimate adjusted hazard ratios of the outcomes comparing DOACs with warfarin. Analyses were conducted independently at each site, with meta-analytical methods used to estimate pooled hazard ratios across sites.Results Of the 59 525 participants, 1967 (3.3%) had a major bleed and 1029 (1.7%) died over a mean follow-up of 85.2 days. The risk of major bleeding was similar for DOAC compared with warfarin use (pooled hazard ratio 0.92, 95% confidence interval 0.82 to 1.03), with the overall direction of the association favouring DOAC use. No difference was found in the risk of death (pooled hazard ratio 0.99, 0.84 to 1.16) for DOACs compared with warfarin use. There was no evidence of heterogeneity across centres, between patients with and without chronic kidney disease, across age groups, or between male and female patients.Conclusions In this analysis of adults with incident venous thromboembolism, treatment with DOACs, compared with warfarin, was not associated with an increased risk of major bleeding or all cause mortality in the first 90 days of treatment.Trial registration Clinical trials NCT02833987.

Objective To determine whether the use of incretin based drugs compared with sulfonylureas is associated with an increased risk of incident pancreatic cancer in people with type 2 diabetes.Design Population based cohort.Setting Large, international, multicentre study combining the health records from six participating sites in Canada, the United States, and the United Kingdom.Participants A cohort of 972 384 patients initiating antidiabetic drugs between 1 January 2007 and 30 June 2013, with follow-up until 30 June 2014.Main outcome measures Within each cohort we conducted nested case-control analyses, where incident cases of pancreatic cancer were matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and duration of follow-up. Hazard ratios and 95% confidence intervals for incident pancreatic cancer were estimated, comparing use of incretin based drugs with use of sulfonylureas, with drug use lagged by one year for latency purposes. Secondary analyses assessed whether the risk varied by class (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) or by duration of use (cumulative duration of use and time since treatment initiation). Site specific hazard ratios were pooled using random effects models.Results During 2 024 441 person years of follow-up (median follow-up ranging from 1.3 to 2.8 years; maximum 8 years), 1221 patients were newly diagnosed as having pancreatic cancer (incidence rate 0.60 per 1000 person years). Compared with sulfonylureas, incretin based drugs were not associated with an increased risk of pancreatic cancer (pooled adjusted hazard ratio 1.02, 95% confidence interval 0.84 to 1.23). Similarly, the risk did not vary by class and evidence of a duration-response relation was lacking.Conclusions In this large, population based study the use of incretin based drugs was not associated with an increased risk of pancreatic cancer compared with sulfonylureas. Although this potential adverse drug reaction will need to be monitored long term owing to the latency of the cancer, these findings provide some reassurance on the safety of incretin based drugs.

ObjectiveTo evaluate the incremental increase in new onset diabetes from higher potency statins compared with lower potency statins when used for secondary prevention.DesignEight population based cohort studies and a meta-analysis.SettingSix Canadian provinces and two international databases from the UK and US.Participants136 966 patients aged ≥40 years newly treated with statins between 1 January 1997 and 31 March 2011.MethodsWithin 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 measuresHospitalisation for new onset diabetes, or a prescription for insulin or an oral antidiabetic drug.ResultsIn 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).ConclusionsHigher 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.

ObjectiveTo quantify an association between acute kidney injury and use of high potency statins versus low potency statins.DesignRetrospective 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.SettingSeven Canadian provinces and two databases in the United Kingdom and the United States. Participants2 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.InterventionA 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 measureRelative hospitalization rates for acute kidney injury. ResultsOf 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). χ2tests for heterogeneity confirmed that the observed association was robust across participating sites.ConclusionsUse 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.

Objective. The purpose of this study was to assess the impacts of individualized prescribing feedback and interactive small group education aimed at encouraging evidence-based prescribing in family/general practice. Methods. A two-by-two factorial randomized controlled trial was carried out involving 200 family physicians in British Columbia, Canada. The physicians met monthly in 28 peer learning groups within the Practice-Based Small Group (PBSG) learning programme. Personalized prescribing feedback related to hypertension was provided through ‘prescribing portraits’ which graphically displayed comparative rates of individual and peer group prescribing, together with a concise guide for evidence-based prescribing. A case-based educational module, containing the same evidence-based message, was discussed in small groups. Groups were matched and randomized into four arms of seven groups each: control (n = 56), prescribing portrait only (n = 48), educational module only (n = 47), both portrait and module (n = 49). The main outcome measure was changes in ‘prescribing preferences’ to new patients among those medications used to treat hypertension (i.e. probability that a patient would receive the evidence-based medication as first-line therapy). Results. Using data from the provincial pharmacy registry (PharmaNet), prescribing preferences for antihypertensive agents were determined for all groups for a 6 month period before and after the interventions, based on 4394 patients receiving a first-line antihypertensive. Significant absolute increases in prescribing preference for thiazides were documented for both the module +0.068 (confidence interval [CI] 0.022–0.115) and the portrait +0.065 (CI 0.018–0.111). Preference in the group receiving both module and portrait increased by +0.115 (CI 0.040–0.189). Conclusions. Evidence-based educational interventions combining personalized prescribing feedback with interactive group discussion can lead to modest but meaningful changes in physician prescribing. Clear messages, proper trial design and sensitive outcomes are necessary to demonstrate these changes.