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Dhalla I.A.,University of Toronto | Dhalla I.A.,Li Ka Shing Knowledge Institute | Mamdani M.M.,University of Toronto | Mamdani M.M.,Applied Health Research Center | And 4 more authors.
Canadian Family Physician | Year: 2011

Objective: To examine whether variation in prescribing at the level of the individual physician is associated with opioid-related mortality. Design: A population-based cross-sectional analysis linking prescription data with records from the Office of the Chief Coroner. Setting: The province of Ontario. Participants: Family physicians in Ontario and Ontarians aged 15 to 64 who were eligible for prescription drug coverage under the Ontario Public Drug Program. Main outcome measures: Variation in family physicians' opioid prescribing and opioid-related mortality among their patients. Results: The 20% of family physicians (n = 1978) who prescribed opioids most frequently issued opioid prescriptions 55 times more often than the 20% who prescribed opioids least frequently. Family physicians in the uppermost quintile also wrote the final opioid prescription before death for 62.7% of public drug plan beneficiaries whose deaths were related to opioids. Physician characteristics associated with greater opioid prescribing were male sex (P = .003), older age (P < .001), and a greater number of years in practice (P < .001). Conclusion: Opioid prescribing varies remarkably among family physicians, and opioid-related deaths are concentrated among patients treated by physicians who prescribe opioids frequently. Strategies to reduce opioid-related harm should include efforts focusing on family physicians who prescribe opioids frequently.


Al-Ansary L.A.,King Saud University | Tricco A.C.,Li Ka Shing Knowledge Institute | Adi Y.,King Saud University | Bawazeer G.,King Saud University | And 6 more authors.
PLoS ONE | Year: 2013

Background: Despite the availability of clinical practice guidelines (CPGs), optimal hypertension control is not achieved in many parts of the world; one of the challenges is the volume of guidelines on this topic and their variable quality. To systematically review the quality, methodology, and consistency of recommendations of recently-developed national CPGs on the diagnosis, assessment and the management of hypertension. Methodology/Principal Findings: MEDLINE, EMBASE, guidelines' websites and Google were searched for CPGs written in English on the general management of hypertension in any clinical setting published between January 2006 and September 2011. Four raters independently appraised each CPG using the AGREE-II instrument and 2 reviewers independently extracted the data. Conflicts were resolved by discussion or the involvement of an additional reviewer. Eleven CPGs were identified. The overall quality ranged from 2.5 to 6 out of 7 on the AGREE-II tool. The highest scores were for "clarity of presentation" (44.4% -88.9%) and the lowest were for "rigour of development" (8.3%-30% for 9 CGPs). None of them clearly reported being newly developed or adapted. Only one reported having a patient representative in its development team. Systematic reviews were not consistently used and only 2 up-to-date Cochrane reviews were cited. Two CPGs graded some recommendations and related that to levels (but not quality) of evidence. The CPGs' recommendations on assessment and non-pharmacological management were fairly consistent. Guidelines varied in the selection of first-line treatment, adjustment of therapy and drug combinations. Important specific aspects of care (e.g. resistant hypertension) were ignored by 6/11 CPGs. The CPGs varied in methodological quality, suggesting that their implementation might not result in less variation of care or in better health-related outcomes. Conclusions/Significance: More efforts are needed to promote the realistic approach of localization or local adaptation of existing high-quality CPGs to the national context. © 2013 Al-Ansary et al.


Alshaikh M.K.,King Saud University | Tricco A.C.,Li Ka Shing Knowledge Institute | Tashkandi M.,Applied Health Research Center | Mamdani M.,Li Ka Shing Knowledge Institute | And 4 more authors.
Journal of Clinical Sleep Medicine | Year: 2012

Study Objectives: To assess the efficacy and safety of sodium oxybate (SXB) in narcolepsy-cataplexy patients. Design: Systematic review and meta-analysis. Patients: Adults with narcolepsy-cataplexy. Interventions: SXB. Measurements and Results: Electronic databases (e.g., MEDLINE) and references of included studies were searched to identify randomized controlled trials (RCTs) assessing the effi cacy and safety of SXB for patients with narcolepsy-cataplexy. Risk of bias was appraised using the Cochrane risk of bias tool. Meta-analysis was conducted in Review Manager Version 5. Six RCTs and 5 companion reports were included after screening 14 full-text articles and 483 citations. All were private-industry funded. SXB (usually 9 g/night) was superior to placebo for reducing mean weekly cataplexy attacks (n = 2 RCTs, mean difference [MD]: -8.5, 95% CI: -15.3, -1.6), increasing maintenance wakefulness test (MWT) (n = 2, MD: 5.18, 95% CI: 2.59-7.78), reducing sleep attacks (n = 2, MD: -9.65, 95% CI: -17.72, -1.59), and increasing Clinical Global Impression scores (n = 3, relative risk, RR: 2.42, 95% CI: 1.77-3.32). SXB did not significantly increase REM sleep versus placebo (n = 2, MD: -0.49, 95% CI: -3.90, 2.92). Patients receiving SXB had statistically more adverse events versus placebo, including nausea (n = 3, relative risk [RR]: 7.74, 95% CI: 3.2, 19.2), vomiting (n = 2, RR: 11.8, 95% CI: 1.6, 89.4), and dizziness (n = 3, RR: 4.3, 95% CI: 1.1, 16.4). Enuresis was not significantly different from placebo (n = 2, RR: 2.6, 95% CI: 0.8, 9.8). All meta-analyses had minimal statistical heterogeneity (p-value > 0.1). Conclusion: Narcolepsy patients on SXB have significant reductions in cataplexy and daytime sleepiness. SXB is well tolerated in patients with narcolepsy, and most adverse events were mild to moderate in severity.


Bhindi B.,A+ Network | Mamdani M.,Applied Health Research Center | Kulkarni G.S.,A+ Network | Kulkarni G.S.,University of Toronto | And 8 more authors.
Journal of Urology | Year: 2015

Purpose We determined if the USPSTF recommendation against prostate specific antigen screening was associated with a change in biopsy and cancer detection rates. Materials and Methods We conducted a time series analysis (October 2008 to June 2013) of prostate biopsies performed at University Health Network (Toronto). Biopsies for active surveillance or solely targeting magnetic resonance imaging detected lesions were excluded from study. Interventional ARIMA models with step functions were used to examine changes in the number of biopsies performed and cancers detected per month. Low risk prostate cancer was defined as no Gleason pattern 4 or greater, 3 or fewer cores involved, or 1/3 or less of the total number of cores involved, and no core with greater than 50% cancer involvement. Intermediate to high grade prostate cancer was defined as Gleason 7-10. Results A total of 3,408 biopsies were performed and 1,601 (47.0%) prostate cancers were detected (low risk prostate cancer 563 [16.5%], intermediate to high grade prostate cancer 914 [26.8%]). The median number of biopsies per month decreased from 58.0 (IQR 54.5-63.0) before the recommendations to 35.5 (IQR 27.0-41.0) afterward (p=0.003), while the median number of patients undergoing first-time biopsy decreased from 42.5 (IQR 37.5-45.5) to 24.0 (IQR 19.0-32.5, p=0.025). The median number of low risk prostate cancers detected per month decreased from 8.5 (IQR 6.5-10.5) to 5.5 (IQR 4.0-7.0, p=0.012), while the median number of intermediate to high grade prostate cancers per month decreased from 17.5 (IQR 14.5-21.5) to 10.0 (IQR 9.0-12.0, p <0.001). Conclusions After the USPSTF recommendation the number of biopsies performed (total and first-time), based on referrals from our catchment area, has decreased. This is likely due to decreased use of prostate specific antigen screening. Although it is encouraging that fewer low risk prostate cancers are being diagnosed, the sudden decrease in the detection rate of Gleason 7-10 prostate cancers is concerning. © 2015 American Urological Association Education and Research, Inc.


Tricco A.C.,Li Ka Shing Knowledge Institute | Chit A.,Glaxosmithkline | Chit A.,University of Toronto | Soobiah C.,Li Ka Shing Knowledge Institute | And 6 more authors.
BMC Medicine | Year: 2013

Background: Influenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains. In the present work we aimed to examine the vaccine efficacy (VE) afforded by influenza vaccines when they are not well matched to circulating strains.Methods: We identified randomized clinical trials (RCTs) through MEDLINE, EMBASE, the Cochrane Library, and references of included RCTs. RCTs reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of matching and non-matching influenza strains were included. Two independent reviewers screened citations/full-text articles, abstracted data, and appraised risk of bias. Conflicts were resolved by discussion. A random effects meta-analysis was conducted. VE was calculated using the following formula: (1 - relative risk × 100%).Results: We included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, VE 54%, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, VE 83%, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months. Differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 75%, 95% CI 41% to 90%) and mismatched influenza B (five RCTs, VE 42%, 95% CI 22% to 56%) estimates among children aged 6 to 36 months. The trivalent inactivated vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults. Statistical heterogeneity was low (I2 <50%) across all meta-analyses, except for the LAIV meta-analyses among children (I2 = 79%).Conclusions: The TIV and LAIV vaccines can provide cross protection against non-matching circulating strains. The point estimates for VE were different for matching versus non-matching strains, with overlapping CIs. © 2013 Tricco et al.; licensee BioMed Central Ltd.

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