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Aim: To examine the likelihood of mortality or rehospitalization following acute coronary syndrome with glyburide versus gliclazide use in adults with type 2 diabetes undergoing cardiac catheterization., Research Design and Methods: This retrospective cohort study used clinical data linked with administrative health data from Alberta, Canada between April 2008 and March 2021. Three methods were used to define exposure to glyburide and gliclazide in the year before catheterization. Multivariable logistic regression was used to compare the likelihood of a composite outcome of 1-year mortality or rehospitalization with use of glyburide versus use of gliclazide., Results: A total of 11 140 individuals with type 2 diabetes had a cardiac catheterization for acute coronary syndrome. Their mean age was 66 years and 31% were female. In the year before catheterization, 5% used glyburide and 19% used gliclazide. Any glyburide or gliclazide exposure in the year before catheterization was associated with a similar likelihood of all-cause mortality or rehospitalization (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 0.93-1.41; p = 0.20). However, current glyburide exposure (aOR 1.37, 95% CI 1.06-1.79; p = 0.018) and long exposure to glyburide (aOR 1.37, 95% CI 1.03-1.83; p = 0.030) were associated with a higher likelihood of the composite outcome compared to current and long exposure to gliclazide, respectively., Conclusions: Current and long exposure to glyburide was associated with a greater likelihood of mortality or rehospitalization following cardiac catheterization for acute coronary syndrome, when compared to similar gliclazide exposure definitions. This study adds further evidence of the need to avoid using glyburide if a sulphonylurea is required for type 2 diabetes management., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objectives: Our aim in this study was to identify the association between place of residence (metropolitan, urban, rural) and guideline-concordant processes of care in the first year of type 2 diabetes management., Methods: We conducted a retrospective cohort study of new metformin users between April 2015 and March 2020 in Alberta, Canada. Outcomes were identified as guideline-concordant processes of care through the review of clinical practice guidelines and published literature. Using multivariable logistic regression, the following outcomes were examined by place of residence: dispensation of a statin, angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB), eye examination, glycated hemoglobin (A1C), cholesterol, and kidney function testing., Results: Of 60,222 new metformin users, 67% resided in a metropolitan area, 10% in an urban area, and 23% in a rural area. After confounder adjustment, rural residents were less likely to have a statin dispensed (adjusted odds ratio [aOR] 0.83, 95% confidence interval [CI] 0.79 to 0.87) or undergo cholesterol testing (aOR 0.86, 95% CI 0.83 to 0.90) when compared with metropolitan residents. In contrast, rural residents were more likely to receive A1C and kidney function testing (aOR 1.14, 95% CI 1.08 to 1.21 and aOR 1.17, 95% CI 1.11 to 1.24, respectively). ACEi/ARB use and eye examinations were similar across place of residence., Conclusions: Processes of care varied by place of residence. Limited cholesterol management in rural areas is concerning because this may lead to increased cardiovascular outcomes., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Antihyperglycemic drug utilization studies are conducted frequently and describe the uptake of new drug therapies across may jurisdictions. An increasingly important, yet often absent, aspect of these studies is the impact of rurality on drug utilization., Objectives: The objective of this study was to explore the association between place of residence (rural, urban, metropolitan) and the use of dipeptidyl peptidase 4 inhibitors (DPP-4i) for first treatment intensification of type 2 diabetes., Methods: A retrospective cohort study was conducted from April 1, 2008 to March 31, 2019 of new metformin users. A multivariable logistic regression analysis was performed to determine the association between place of residence (using postal codes) and likelihood of DPP-4i dispensing., Results: After adjusting for confounders, analysis revealed that rural-dwellers are less likely to have a DPP-4i dispensed, compared with metropolitan-dwellers (aOR:0.64; 95%CI:0.61-0.67) and over-time, the uptake in rural areas was slower., Conclusions: This study demonstrates that rurality can have an impact on drug therapy decisions at first treatment intensification, with respect to the utilization of new therapies., Competing Interests: No potential conflicts of interest relevant to this article were reported. S.H.S. is supported as the Chair in Patient Health Management, jointly held by the Faculty of Pharmacy and Pharmaceutical Sciences and Faculty of Medicine and Dentistry, University of Alberta. This study is based in part on data provided by Alberta Health. The interpretation and conclusions contained herein are those of the researchers and do not necessarily represent the views of the Government of Alberta. Neither the Government of Alberta nor Alberta Health express any opinion in relation to this study., (© 2024 The Authors.)

Objective: To develop a machine-learning (ML) model using administrative data to estimate risk of adverse outcomes within 30-days of a benzodiazepine (BZRA) dispensation in older adults for use by health departments/regulators., Design, Setting and Participants: This study was conducted in Alberta, Canada during 2018-2019 in Albertans 65 years of age and older. Those with any history of malignancy or palliative care were excluded., Exposure: Each BZRA dispensation from a community pharmacy served as the unit of analysis., Main Outcomes and Measures: ML algorithms were developed on 2018 administrative data to predict risk of any-cause hospitalization, emergency department visit or death within 30-days of a BZRA dispensation. Validation on 2019 administrative data was done using XGBoost to evaluate discrimination, calibration and other relevant metrics on ranked predictions. Daily and quarterly predictions were simulated on 2019 data., Results: 65,063 study participants were included which represented 633,333 BZRA dispensation during 2018-2019. The validation set had 314,615 dispensations linked to 55,928 all-cause outcomes representing a pre-test probability of 17.8%. C-statistic for the XGBoost model was 0.75. Measuring risk at the end of 2019, the top 0.1 percentile of predicted risk had a LR + of 40.31 translating to a post-test probability of 90%. Daily and quarterly classification simulations resulted in uninformative predictions with positive likelihood ratios less than 10 in all risk prediction categories. Previous history of admissions was ranked highest in variable importance., Conclusion: Developing ML models using only administrative health data may not provide health regulators with sufficient informative predictions to use as decision aids for potential interventions, especially if considering daily or quarterly classifications of BZRA risks in older adults. ML models may be informative for this context if yearly classifications are preferred. Health regulators should have access to other types of data to improve ML prediction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We explore, experimentally and theoretically, the emergence of coherent coupled oscillations and synchronization between a pair of non-Hermitian, stochastic, opto-mechanical oscillators, levitated in vacuum. Each oscillator consists of a polystyrene microsphere trapped in a circularly polarized, counter-propagating Gaussian laser beam. Non-conservative, azimuthal forces, deriving from inhomogeneous optical spin, push the micro-particles out of thermodynamic equilibrium. For modest optical powers each particle shows a tendency towards orbital circulation. Initially, their stochastic motion is weakly correlated. As the power is increased, the tendency towards orbital circulation strengthens and the motion of the particles becomes highly correlated. Eventually, centripetal forces overcome optical gradient forces and the oscillators undergo a collective Hopf bifurcation. For laser powers exceeding this threshold, a pair of limit cycles appear, which synchronize due to weak optical and hydrodynamic interactions. In principle, arrays of such Non-Hermitian elements can be arranged, paving the way for opto-mechanical topological materials or, possibly, classical time crystals. In addition, the preparation of synchronized states in levitated optomechanics could lead to new and robust sensors or alternative routes to the entanglement of macroscopic objects., (© 2023. Springer Nature Limited.)

Objective: To construct a machine-learning (ML) model for health systems with organised falls prevention programmes to identify older adults at risk for fall-related admissions., Design: This prognostic study used population-level administrative health data to develop an ML prediction model., Setting: This study took place in Alberta, Canada during 2018-2019., Participants: Albertans aged 65 and older with at least one prior admission. Those with palliative conditions or emigrated out of Alberta were excluded., Exposure: Unit of analysis was the individual person., Main Outcomes/measures: We identified fall-related admissions. A CatBoost model was developed on 2018 data to predict risk of fall-related emergency department visits or hospitalisations. Temporal validation was done using 2019 data to evaluate model performance. We reported discrimination, calibration and other relevant metrics measured at the end of 2019 on both ranked predictions and predicted probability thresholds. A cost-savings simulation was performed using 2019 data., Results: Final number of study participants was 224 445. The validation set had 203 584 participants with 19 389 fall-related events (9.5% pretest probability) and an ML model c-statistic of 0.70. The highest ranked predictions had post-test probabilities ranging from 40% to 50%. Net benefit analysis presented mixed results with some net benefit using the ML model in the 6%-30% range. The top 50 percentile of predicted risks represented nearly $C60 million in health system costs related to falls. Intervening on the top 25 or 50 percentiles of predicted risk could realise substantial (up to $C16 million) savings., Conclusion: ML prediction models based on population-level administrative data can assist health systems with fall prevention programmes identify older adults at risk of fall-related admissions and reduce costs. ML predictions based on ranked predictions or probability thresholds could guide subsequent interventions to mitigate fall risks. Increased access to diverse forms of data could improve ML performance and further reduce costs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine the intersection between location of residence along the rural-urban continuum (metropolitan, urban, and rural) and sulfonylurea dispensation records for the management of type 2 diabetes., Research Design and Methods: This retrospective cohort study used administrative health records of adult new metformin users between April 2008 and March 2019 in Alberta, Canada. Multivariable logistic regression was performed to examine the association between sulfonylurea-based treatment intensification and location of residence., Results: Treatment was intensified in 66,084 (38%) of 171,759 new metformin users after a mean of 1.5 years. At treatment intensification, mean age was 55 years, 62% of users were male, and 27% were rural residents. The most common antihyperglycemic drug, given to 30,297 people (46%) for treatment intensification, was a sulfonylurea. At the beginning of our observation period, the proportion of people dispensed a sulfonylurea at first treatment intensification was highest in rural (57%), compared with urban (54%) and metropolitan (52%) areas (P = 0.009). Although proportions decreased over time across the province, rural residents continued to constitute the highest proportion of sulfonylurea users (45%), compared with urban (35%) and metropolitan (37%) residents (P < 0.001), and the trend away from sulfonylurea use was delayed by ∼4 years for rural residents. Adjusting for potential sources of confounding, rural residence was associated with a significantly higher likelihood of using a sulfonylurea compared with metropolitan residence (adjusted odds ratio 1.34; 95% CI 1.29-1.39)., Conclusions: Variation in sulfonylurea dispensation across the rural-urban continuum provides a basis for continued research in the differences in process of care by location., (© 2023 by the American Diabetes Association.)

Background: Pharmacists in Alberta have been authorized to administer vaccines and other medications by injection for more than 10 years; however, little is known about the provision of this service and their opinions regarding this service. Understanding pharmacists' experiences regarding injection services would inform development of strategies to improve provision of injection services., Objectives: To describe the actions related to administering an injection, including identification of commonly administered medications, and to identify perceived barriers and facilitators pharmacists face when providing injection services., Methods: An online survey was developed and loaded into REDCap, and e-mail invitations were sent to 5714 pharmacists registered with the Alberta College of Pharmacy in October 2020. Responses were analyzed using descriptive statistics. Pharmacists who administered at least one injection in the previous year were considered active providers, and their opinions regarding injection services were compared with nonactive providers., Results: A total of 397 pharmacists responded to our survey, mean age was 42 years, 66% were female, 82% were community pharmacists, and 90% were active providers. The most common injection, administered by 98% of active providers, was influenza vaccine, followed by vitamin B12 (95%), herpes zoster vaccine (88%), hepatitis vaccines (86%), and pneumococcal vaccines (82%). Nonactive providers were more likely than active providers to report that comfort with administering injections (P < 0.001) and managing adverse reactions (P = 0.013) were moderate or major barriers to providing injections. More than 60% of pharmacists indicated that access and automated reporting to the provincial immunization registry would be essential to increasing the frequency of providing injection services., Conclusion: We identified that Alberta pharmacists administer a wide variety of vaccines and other medications by injection. Respondents identified several barriers and facilitators to providing these services. Addressing these barriers may help improve provision of injection services by pharmacists., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Importance: Machine learning approaches can assist opioid stewardship by identifying high-risk opioid prescribing for potential interventions., Objective: To develop a machine learning model for deployment that can estimate the risk of adverse outcomes within 30 days of an opioid dispensation as a potential component of prescription drug monitoring programs using access to real-world data., Design, Setting, and Participants: This prognostic study used population-level administrative health data to construct a machine learning model. This study took place in Alberta, Canada (from January 1, 2018, to December 31, 2019), and included all patients 18 years and older who received at least 1 opioid dispensation from a community pharmacy within the province., Exposures: Each opioid dispensation served as the unit of analysis., Main Outcomes and Measures: Opioid-related adverse outcomes were identified from administrative data sets. An XGBoost model was developed on 2018 data to estimate the risk of hospitalization, an emergency department visit, or mortality within 30 days of an opioid dispensation; validation on 2019 data was done to evaluate model performance. Model discrimination, calibration, and other relevant metrics are reported using daily and weekly predictions on both ranked predictions and predicted probability thresholds using all data from 2019., Results: A total of 853 324 participants represented 6 181 025 opioid dispensations, with 145 016 outcome events reported (2.3%); 46.4% of the participants were men and 53.6% were women, with a mean (SD) age of 49.1 (15.6) years for men and 51.0 (18.0) years for women. Of the outcome events, 77 326 (2.6% pretest probability) occurred within 30 days of a dispensation in the validation set (XGBoost C statistic, 0.82 [95% CI, 0.81-0.82]). The top 0.1 percentile of estimated risk had a positive likelihood ratio (LR) of 28.7, which translated to a posttest probability of 43.1%. In our simulations, the weekly measured predictions had higher positive LRs in both the highest-risk dispensations and percentiles of estimated risk compared with predictions measured daily. Net benefit analysis showed that using machine learning prediction may not add additional benefit over the entire range of probability thresholds., Conclusions and Relevance: These findings suggest that prescription drug monitoring programs can use machine learning classifiers to identify patients at risk of opioid-related adverse outcomes and intervene on high-risk ranked predictions. Better access to available administrative and clinical data could improve the prediction performance of machine learning classifiers and thus expand opioid stewardship efforts.

Objectives: Depression is a known risk factor for poor medication adherence, but it is unclear whether depression treatment affects adherence rates. In this study, we examined the association between pharmacologic treatment of a new depressive episode and subsequent adherence to oral antihyperglycemic medications., Methods: In this retrospective cohort study, we used administrative health data to follow adult new metformin users in Alberta, Canada, between 2008 and 2018. Depressive episodes starting ≥1 year after metformin initiation were identified and individuals starting antidepressant treatment within the first 90 days were compared with those who did not. The proportion of days covered (PDC) with oral antihyperglycemic medications in the subsequent year (days 91 to 455) was used to estimate adherence. The association between antidepressant treatment and poor adherence (PDC<0.8) was examined using multivariate logistic regression models., Results: A new depressive episode occurred in 6,201 people, with a mean age of 56.0 (standard deviation [SD], 15.4) years. Of this cohort, 3,303 (53.2%) were women. Mean PDC was 0.55 (SD, 0.41); 924 (57.0%) of 1,621 people who started antidepressant treatment and 2,709 (59.2%) of 4,580 controls had poor adherence (p=0.13). After adjusting for baseline comorbidities and other characteristics, antidepressant treatment was associated with a lower likelihood of poor adherence (adjusted odds ratio, 0.85; 95% confidence interval, 0.75 to 0.96; p=0.007)., Conclusions: Although overall adherence to antihyperglycemic medications was low after onset of a depressive episode, antidepressant treatment was associated with a lower likelihood of poor adherence., (Copyright © 2022 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Background: We sought to develop machine learning (ML) models trained on administrative data which predict risk of readmission in patients with heart failure and to evaluate and compare the ML model with the currently used LaCE score using clinically informative metrics., Methods and Results: This prognostic study was conducted in Alberta, Canada, on 9845 patients with confirmed heart failure admitted to hospital between 2012 and 2019. The outcome was unplanned all-cause hospital readmission within 30 days of discharge. We used 80% of the data for the ML model development and 20% for independent validation. We reported, using the validation set, c-statistics (area under the receiver operating characteristic curves)and performance metrics (likelihood ratio, positive predictive values) for the XGBoost model and a modified LaCE score within their respective predictive thresholds. Boosted tree-based classifiers had higher area under the receiver operating characteristic curves (0.65 for XGBoost) compared with others (0.58 for neural networks) and 0.57 for the modified LaCE. Within the predicted threshold range of the XGBoost classifier, the positive likelihood ratio was 1.00 at the low end of predicted risk and 6.12 at the high end, resulting in a positive predictive value (post-test probability) range of 21%-62%; the pretest probability of readmission was 20.9% using prevalence. The corresponding positive likelihood ratios and positive predictive values across LaCE score thresholds were 1.00-1.20 and 21%-24%, respectively., Conclusions: Despite predicting readmissions better than the LaCE, even the best ML model trained on administrative health data (XGBoost) did not provide substantially informative prediction performance as it only generated a moderate shift from pre to post-test probability. Health systems wishing to deploy such a tool should consider training ML models with additional data. Adding other techniques like natural language processing, along with ML, to use other clinical information (like chart notes) might improve prediction performance., Competing Interests: Conflict of interest None., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: In this study, we aimed to characterize time to treatment intensification (TTI) in people on metformin with uncontrolled hyperglycemia, and estimated the frequency of physician visits until intensification., Methods: This work was a cohort study of Albertan adults with glycated hemoglobin (A1C) of >7.5% after at least 3 months of metformin monotherapy, using administrative databases from 2009 to 2018, with each subject followed for up to 4 years. Therapeutic intensification was defined as dispensation of an additional class of antihyperglycemic medication. Median TTI and the median number of physician visits were estimated from Kaplan-Meier functions within age/A1C strata. A Cox proportional hazards model was fitted to examine predictors of therapeutic intensification., Results: We included 38,846 people (average age, 57 years; 37% female; mean A1C, 8.8%). Overall, therapeutic intensification was observed in 23,077 (59%; 40% at 1 year). Median TTI was 1.4 years, varying from 0.7 years (A1C >8.5%, age <65 years) to 3.3 years (age ≥75 years, any A1C). The median number of physician visits until intensification was 9, varying between 5 (A1C >8.5%, age <65 years) and ≥30 (age ≥75 years); 93% of people awaiting intensification had at least 2 visits by 1 year. Higher A1C and younger age were the strongest predictors of intensification. Results were similar in people with ischemic heart disease., Conclusions: Despite ample contacts with community physicians, TTI exceeds the 6-month target recommended by guidelines, particularly in older adults. Further study is needed to better understand these foregone opportunities as guidelines call for wider promulgation of agents with cardiorenal benefits., (Copyright © 2021 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Aims: The association between depression and poor medication adherence is based on cross-sectional studies and cohort studies that measure adherence rates after depression status is determined. However, depressive symptoms occur well before diagnosis. This study examined adherence patterns in the year before a depressive episode., Methods: This retrospective cohort study followed new metformin users identified in Alberta Health's administrative data between 2008 and 2018. Depressive episodes starting ≥1 year after metformin initiation were identified using a validated case definition. Controls were randomly assigned a pseudo depression date. Adherence to oral antihyperglycemic medications was estimated using proportion of days covered (PDC) and group-based trajectory models to explore the association between depression and poor adherence (PDC<0.8)., Results: A depressive episode occurred in 17,418 (10.6%) of 165,056 new metformin users. Individuals with depression were more likely to have poor adherence compared to controls (adjusted odds ratio 1.21; 95% CI 1.17, 1.26). Five trajectories were identified: nearly perfect adherence (PDC >0.95 [34.8% of cohort]), discontinued (PDC=0 [18.3% of cohort], poor initial adherence (PDC 0.75) that declined either rapidly (9.2% of cohort) or gradually (30.1% of cohort), and poor initial adherence (PDC 0.26) that increased gradually (7.6% of cohort). Individuals with depression were more likely to be in one of the four trajectories of poor adherence compared to controls (adjusted odds ratio 1.24; 95% CI 1.19-1.29)., Conclusions: Poor medication adherence occurs in the year before a depressive episode; therefore, poor medication use patterns could be used as an early warning sign for depression., (© 2020 Diabetes UK.)

Aim: To examine whether early addition of sitagliptin to metformin is associated with a delay in type 2 diabetes progression., Methods: Administrative health records from Alberta, Canada, for the period April 2008 to March 2015, were used to conduct a retrospective cohort study in new metformin users. People who started sitagliptin on the same day they initiated metformin therapy were compared with those who added sitagliptin later. Insulin initiation served as a surrogate marker for diabetes progression, and multivariable logistic regression models were used to evaluate the association with sitagliptin addition (costart vs later use). A mixed-effects linear regression model was used to examine the effect of timing of sitagliptin addition on HbA 1c change over 1 year., Results: The mean (sd) age of the 8764 people who used sitagliptin was 52.1 (11.1) years, 5665 (64.6%) were men, and 1153 (13.2%) started sitagliptin on the same day as metformin. Insulin was added to the therapy of 173 (15.0%) costarters and 1453 (19.1%) later sitagliptin users. The adjusted odds ratio for adding insulin was 0.76 (95% CI 0.64 to 0.90) in favour of costarting sitagliptin. HbA 1c levels decreased in both groups 1 year after starting sitagliptin, with costarters having a significantly greater reduction [absolute between-group difference of 0.5% (95% CI 0.3 to 0.7)] compared with later sitagliptin users., Conclusion: Costarting drug therapy with sitagliptin and metformin was associated with a lower likelihood of disease progression in people with type 2 diabetes compared with adding sitagliptin later., (© 2019 Diabetes UK.)

Objectives: The primary objective was to determine medication-taking behaviours and factors influencing adherence in patients with mental illness and recent homelessness. Secondary objectives were to explore patients' perceptions on mobile technology use to support adherence., Methods: A constructivist approach and qualitative description method was used. The sample population consisted of patients with recent homelessness and mental illness affiliated with a community-based outreach programme in Canada. Participants were purposefully selected; semi-structured interviews were conducted to elicit information on medication-taking strategies and mobile technology to support adherence. A standardized questionnaire collected demographic and medical information; the Medication Adherence Rating Scale (MARS) was used to evaluate self-reported adherence. Questionnaire data were analysed using summary descriptive statistics. Interview data were subject to qualitative content analysis., Key Findings: Fifteen participants with a mean age of 44 years were included. The mean MARS score ± standard deviation was 7.3 ± 1.5. Themes arising from the data included patient factors (i.e. insight, attitudes towards medications, coping strategies) and external factors (i.e. therapeutic alliance, family support that impacted adherence) and technology use and health. Eight participants (53%) had access to a mobile phone. There was a moderate interest in the use of mobile technology to support adherence, with cost and technology literacy identified as barriers., Conclusion: External supports and individual medication management strategies were important in supporting medication adherence in this patient group. Perceived need for mobile technology, in addition to existing supports for adherence, was not high. Challenges accessing and maintaining consistent mobile technology and individual preferences should be considered when developing mobile technology-based interventions., (© 2020 Royal Pharmaceutical Society.)

We demonstrate an effect whereby stochastic, thermal fluctuations combine with nonconservative optical forces to break detailed balance and produce increasingly coherent, apparently deterministic motion for a vacuum-trapped particle. The particle is birefringent and held in a linearly polarized Gaussian optical trap. It undergoes oscillations that grow rapidly in amplitude as the air pressure is reduced, seemingly in contradiction to the equipartition of energy. This behavior is reproduced in direct simulations and captured in a simplified analytical model, showing that the underlying mechanism involves nonsymmetric coupling between rotational and translational degrees of freedom. When parametrically driven, these self-sustained oscillators exhibit an ultranarrow linewidth of 2.2 μHz and an ultrahigh mechanical quality factor in excess of 2 × 10 8 at room temperature. Last, nonequilibrium motion is seen to be a generic feature of optical vacuum traps, arising for any system with symmetry lower than that of a perfect isotropic microsphere in a Gaussian trap., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

Objectives: Our aim in this study was to determine whether differences exist in time to treatment intensification in newly treated type 2 diabetes patients in Canada and the United States (US)., Methods: Two separate retrospective cohorts of diabetes patients were used from Canada and the US. Time to treatment intensification (i.e. addition of a second antihyperglycemic agent after initial metformin use) was determined using multivariate Cox proportional hazard models., Results: Among new metformin users in 2004‒2007 (2,116 Canadians and 2,631 Americans) >65 years of age, the median time to treatment intensification was 362 days for Canadians and 170 days for Americans (adjusted hazard ratio, 1.99; 95% confidence interval, 1.69 to 2.36). In a second cohort of all adult ages with clinical data between 2008 and 2010 (23,022 Canadians and 19,318 Americans), the median time to treatment intensification was 197 days for Canadians and 119 days for Americans (adjusted hazard ratio, 5.62; 95% confidence interval, 5.246 to 6.029). At treatment intensification, the mean glycated hemoglobin was 9.0% (standard deviation, 2.0) in Canada and 8.6% (standard deviation, 2.2) in the US (p<0.01)., Conclusions: Although clinical practice guidelines are similar between Canada and the US, Canadian clinicians have historically demonstrated more clinical inertia compared with their US counterparts with respect to intensifying antihyperglycemic therapy. It is relatively unknown whether these differences currently exist or whether Canadian clinicians have closed the gap., (Copyright © 2019 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Aims: Pneumococcal vaccination is recommended in diabetes because of the high risk for invasive pneumococcal disease and mortality; however, vaccination rates are below recommended targets. This study was conducted to identify possible reasons behind the low rate of vaccine uptake., Methods: We examined baseline information from the Alberta Caring for Diabetes study, a prospective cohort study of 2040 adults with type 2 diabetes. Patients were recruited between December 2011 and December 2013. The baseline survey collected information on a wide range of socio-demographic characteristics, disease and management information, as well as health status measurements and health service utilization. Multivariable logistic regression analyses were conducted to identify factors associated with self-reported pneumococcal vaccination status., Results: Mean age was 64 (SD 11) years, 45% were women, mean duration of diabetes was 12 (SD 10) years, and 1090 (53%) were vaccinated. Age≥65 years (adjusted odds ratio [aOR] 2.52; 95% CI: 1.98-3.20), respiratory disease (aOR 1.50; 95% CI: 1.17-1.93), and cancer (aOR 1.45; 95% CI: 1.08-1.94) were independently associated with pneumococcal vaccination. In addition, women, retirees, people with diabetes≥10 years, people using antihypertensive medications or insulin, and those who had their HbA 1c , kidney function, or their weight or waist circumference measured by a healthcare professional in the past year were more likely to have been vaccinated., Conclusion: Based on this information, future programs aimed at people aged<65 years old, men, those who are currently working, those recently diagnosed with diabetes, and those with few comorbidities could have the most potential for improving pneumococcal vaccine uptake in people with diabetes., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objective: The objective of this study is to characterise concurrent use of benzodiazepine receptor modulators and opioids among prescription opioid users in Alberta in 2017., Design: A population based retrospective study., Setting: Alberta, Canada, in the year 2017., Participants: All individuals in Alberta, Canada, with at least one dispensation record from a community pharmacy for an opioid in the year 2017., Exposure: Concurrent use of a benzodiazepine receptor modulator and opioid, defined as overlap of supply for both drugs for at least 1 day., Main Outcome Measures: Prevalence of concurrency was estimated among subgroups of patient characteristics that were considered clinically relevant or associated with inappropriate medication use., Results: Among the 547 709 Albertans who were dispensed opioid prescriptions in 2017, 132 156 (24%) also received prescriptions for benzodiazepine receptor modulators. There were 96 581 (17.6%) prescription opioid users who concurrently used benzodiazepine receptor modulators with an average of 98 days (SD=114, 95% CI 97 to 99) of total cumulative concurrency and a median of 37 days (IQR 10 to 171). The average longest duration of consecutive days of concurrency was 45 (SD=60, 95% CI 44.6 to 45.4) with a median of 24 days (IQR 8 to 59). Concurrency was more prevalent in females, patients using an average daily oral morphine equivalent >90 mg, opioid dependence therapy patients, chronic opioid users, patients utilising a high number of unique providers, lower median household incomes and those older than 65 (p value<0.001 for all comparisons)., Conclusions: Concurrent prescribing of opioids and benzodiazepine receptor modulators is common in Alberta despite the ongoing guidance of many clinical resources. Older patients, those taking higher doses of opioids, and for longer durations may be at particular risk of adverse outcomes and may be worthy of closer follow-up for assessment for dose tapering or discontinuations. As well, those with higher healthcare utilisation (seeking multiple providers) should also be closely monitored. Continued surveillance of concurrent use of these medications is warranted to ensure that safe drug use recommendations are being followed by health providers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Healthy user bias, whereby health-seeking patients are more likely to initiate preventive therapies and engage in healthy lifestyle behaviours, is well known in observational studies, particularly with statins. However, its influence in studies of oral antihyperglycemic therapies is unknown. We sought to explore the healthy user effects in metformin users vs. nonusers on various health outcomes that should not be associated with metformin use., Methods: We conducted a retrospective cohort study using data from Alberta, between 2008 and 2015, to examine the association between metformin use and various health outcomes., Results: We identified 135,301 new users of oral antihyperglycemic agents. The mean age was 55 years, 75,949 (56%) were men and 130,725 (97%) had had at least 1 metformin prescription during a mean follow-up period of 3.4 years. Metformin users were less likely to be involved in accident-related events (adjusted hazard ratio [aHR] 0.90; 95% CI 0.85 to 0.96), were more likely to have preventive screening services (aHR 1.16; 95% CI 1.11 to 1.21), were less likely to experience other clinical events, such as asthma and gout attacks (aHR 0.90; 95% CI 0.84 to 0.97), and had lower risks for all-cause mortality (aHR 0.57; 95% CI 0.51 to 0.63) compared to nonusers., Conclusions: Our results suggest that metformin users are more likely to initiate preventive therapies and engage in other healthy behaviours. Failure to account for these behaviours may introduce healthy user bias into studies evaluating the effects of oral antihyperglycemic therapies., (Copyright © 2018 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Background: Heart failure (HF) exacerbations often relate to poor self-care. Education programs improve outcomes, but are resource-intensive. We developed a video-based educational intervention and evaluated it in patients with HF., Methods: Congestive Heart Failure O utreach P rogram of E ducation was a pragmatic multicenter randomized trial. We included subjects with HF if they were hospitalized, seen in the emergency department (ED), or high-risk outpatients, and randomized them to intervention or control. Intervention included a 20-minute video, supplementary booklet, and 3 bimonthly newsletters focusing on salt and fluid restriction, daily weights, and medications. Subjects watched the video and were encouraged to review it at home, along with the booklet/newsletters. Control subjects received the booklet only. The primary outcome was the difference in cardiovascular hospitalizations or ED visits between groups at 6 months. Secondary outcomes included clinical events and in-hospital days., Results: We recruited 539 subjects from 22 centers in Canada and the United States. Baseline characteristics were similar in both groups: 64% were male and had a mean age of 66 (± 13) years, mean ejection fraction 31% (± 13.5), and 65% New York Heart Association Functional Classification III/IV. The primary outcome occurred in 57 subjects (21%) in the intervention group compared with 61 subjects (23%) in the control group ( P  = 0.66). There were no significant differences in prespecified secondary outcomes; however, death occurred in 18 subjects (7%) in the intervention group and 33 subjects (12%) in the control group ( P  = 0.03)., Conclusion: Video education on self-care did not reduce hospitalizations or ED visits in patients with HF. Of note, mortality was lower in the intervention group., (© 2019 Canadian Cardiovascular Society. Published by Elsevier Inc.)

Silicon nanowires are held and manipulated in controlled optical traps based on counter-propagating beams focused by low numerical aperture lenses. The double-beam configuration compensates light scattering forces enabling an in-depth investigation of the rich dynamics of trapped nanowires that are prone to both optical and hydrodynamic interactions. Several polarization configurations are used, allowing the observation of optical binding with different stable structure as well as the transfer of spin and orbital momentum of light to the trapped silicon nanowires. Accurate modeling based on Brownian dynamics simulations with appropriate optical and hydrodynamic coupling confirms that this rich scenario is crucially dependent on the non-spherical shape of the nanowires. Such an increased level of optical control of multiparticle structure and dynamics open perspectives for nanofluidics and multi-component light-driven nanomachines.

We provide a vivid demonstration of the mechanical effect of transverse spin momentum in an optical beam in free space. This component of the Poynting momentum was previously thought to be virtual, and unmeasurable. Here, its effect is revealed in the inertial motion of a probe particle in a circularly polarized Gaussian trap, in vacuum. Transverse spin forces combine with thermal fluctuations to induce a striking range of non-equilibrium phenomena. With increasing beam power we observe (i) growing departures from energy equipartition, (ii) the formation of coherent, thermally excited orbits and, ultimately, (iii) the ejection of the particle from the trap. As well as corroborating existing measurements of spin momentum, our results reveal its dynamic effect. We show how the under-damped motion of probe particles in structured light fields can expose the nature and morphology of optical momentum flows, and provide a testbed for elementary non-equilibrium statistical mechanics.

BACKGROUND - A variety of methods are used to define exposure in pharmacoepidemiologic studies. Although each method has known biases, the relative effect of these biases on an observed association has not been fully examined. OBJECTIVE - To explore the influence of different exposure definitions on estimates, using the association between metformin and all-cause mortality as a proto-typical model. METHODS - New users of oral anti-hyperglycemic drugs were identified using administrative health databases from Alberta, Canada between 1998 and 2010. Drug exposure was described using definitions that are commonly used in observational studies. All analyses included the same covariates of age, gender, and a comorbidity score, and subjects not exposed to metformin served as the reference group. The measure of association was assessed using a Cox Proportional Hazards model for cohort studies and conditional logistic regression for case-control studies. RESULTS - We identified 64,293 new oral anti-hyperglycemic drugs users; mean age 68.9 years, 33,131 (52%) males, and 24,745 (39%) deaths during a mean follow-up of 6 years.  In adjusted models, the association between metformin and mortality ranged from 0.23 (95% CI 0.22-0.25) to 0.92 (95% CI 0.88-0.95) reduction. Most metformin exposure definitions, however, provided estimates in the 0.6-0.8 reduction range, aligning with the results of previous observational studies. CONCLUSIONS - The variety of exposure definitions tested in this analysis produced a wide range of associations between metformin and mortality risk. Therefore, pharmacoepidemiological studies should implement sensitivity analyses including at least two exposure definitions to provide more robust and potentially valid study estimates.

Objective: To determine whether use of a compensation plan to remunerate pharmacists for clinical pharmacy services was associated with the number of diabetes management activities provided., Methods: Alberta pharmacists were asked about compensation plan use and frequency they provide a list of 80 diabetes management activities., Key Findings: A total of 168 community pharmacists responded to the survey. When compensation plan use, diabetes-specific training, practice characteristics and additional authorizations were incorporated into a factorial ANOVA, pharmacists who used the compensation plan reported a mean of 42.9 (95% CI 39.4 to 46.4) diabetes management activities, while those who did not reported a mean of 29.9 (95% CI 21.4 to 38.4) activities (P = 0.016)., Conclusions: After considering other important influencing factors, use of the compensation plan is positively correlated with the number of diabetes management activities pharmacists provided., (© 2017 Royal Pharmaceutical Society.)

Background: In the past decade, pharmacist practice has evolved tremendously in Canada, but the scope of practice varies substantially from one province to another., Objective: To describe pharmacists' scopes of practice relevant to prescribing within various jurisdictions of Canada, using the prescribing model in Alberta (authors' province) as the reference point., Methods: This cross-sectional survey consisted of clinical scenarios for emergency prescribing, adapting or renewing a prescription, and initial-access prescribing for a chronic disease. Pharmacists were asked about their ability to administer injections and to order or access the results of laboratory tests, as well as certification and training requirements and reimbursement models., Results: Thirteen pharmacists representing Canadian provinces other than Alberta were surveyed in late 2015, for comparison with Alberta. With specific reference to the scenarios presented, pharmacists were able to prescribe in an emergency in 9 of the 10 provinces, renew prescriptions in all provinces, and adapt prescriptions in 6 provinces. Three provinces required that pharmacists have collaborative practice agreements identifying a specific practice area in order to initiate a prescription for a chronic disease (with 6-12 pharmacists per province having such agreements). Alberta required pharmacists to have authorization, based on a detailed application, in order to initiate any provincially regulated drug (with about 1150 pharmacists having this authorization). Pharmacists were allowed to administer vaccines in 9 provinces, and 5 provinces allowed pharmacists to administer drugs by injection. Three provinces had systems in place for pharmacists to access laboratory test results, and 2 allowed pharmacists to order laboratory tests. Five provinces had government-reimbursed programs in place for select prescribing services; however, all 9 provinces with public vaccination programs reimbursed pharmacists for this service., Conclusions: Pharmacist prescribing differs among Canadian provinces. Although most provinces allow emergency prescribing and renewal or adaptation of prescriptions by pharmacists, only 4 provinces allow prescription initiation, with variable criteria and scope. Despite some progress to enhance patient flow through the health care system (e.g., by allowing pharmacists to extend prescriptions), further work should be pursued to harmonize clinical practices across Canada and to enable pharmacists to initiate and manage drug therapy., Competing Interests: Competing interests: Tammy Bungard has received speaker’s honoraria from Bayer and Bristol-Myers Squibb, as well as unrestricted research grants from Bristol-Myers Squibb-Pfizer, and Bayer for work outside the topic of this article. Surya Bhatia and Scot Simpson have nothing to disclose.

Background: Inducement programs can promote customer loyalty; however, the clinical effects of these programs are unknown., Objective: To examine relationships among inducement program use, medication adherence, and health outcomes., Methods: Alberta residents with ≥ 1 physician visit for diabetes or hypertension between April 2008 and March 2014 were eligible for this study and included if they were new statin users and alive at least 455 days after the first statin dispensation. Group assignment was based on whether all statin dispensations in the first year were obtained from pharmacies with or without inducement programs. Discontinuation was defined as no statin dispensations between 275 and 455 days after the first statin dispensation. Acute coronary syndrome (ACS) hospitalizations or deaths were identified between 456 days and 3 years after the first statin dispensation. Multivariable regression analyses were conducted to examine relationships among inducement program use, discontinuation, and ACS events., Results: Among the 159 998 new statin users, mean age was 60.2 (±13.7) years and 67 534 (42%) were women. Statin discontinuation occurred in 22 455 (28.9%) of 77 803 inducement group participants and 25 816 (31.4%) of 82 195 noninducement group participants (adjusted odds ratio = 0.88; 95% CI = 0.86-0.90). Risk of an ACS event was similar between groups (adjusted hazard ratio = 1.00; 95% CI 0.92-1.08); however, discontinuing statin therapy was associated with a higher risk of an ACS event (adjusted hazard ratio = 1.27; 95% CI = 1.16-1.39)., Conclusions: Inducement programs are associated with better adherence and not directly associated with risk of health outcomes.

Multiple scattering of light induces structured interactions, or optical binding forces, between collections of small particles. This has been extensively studied in the case of microspheres. However, binding forces are strongly shape dependent: here, we turn our attention to dielectric nanowires. Using a novel numerical model we uncover rich behavior. The extreme geometry of the nanowires produces a sequence of stationary and dynamic states. In linearly polarized light, thermally stable ladder-like structures emerge. Lower symmetry, sagittate arrangements can also arise, whose configurational asymmetry unbalances the optical forces leading to nonconservative, translational motion. Finally, the addition of circular polarization drives a variety of coordinated rotational states whose dynamics expose fundamental properties of optical spin. These results suggest that optical binding can provide an increased level of control over the positions and motions of nanoparticles, opening new possibilities for driven self-organization and heralding a new field of self-assembling optically driven micromachines.

Background: Undiagnosed diabetes can create significant management issues for seniors., Objectives: To evaluate the effectiveness of two diabetes risk surveys-the Canadian Diabetes Risk Assessment Questionnaire (CANRISK) and the Finnish Diabetes Risk Score (FINDRISC)-to identify elevated blood glucose levels in seniors., Methods: A cross-sectional study was conducted in senior living facilities in Edmonton, Alberta, Canada. Those with known diabetes, without capacity, considered frail, or unable to communicate in English were excluded. Participants completed the CANRISK and FINDRISC surveys and had their glycated hemoglobin A 1c (HbA 1c ) measured. Correlations between seniors with elevated risk on the surveys and an HbA 1c value of 6.5% or higher or 6.0% and higher were assessed., Results: In this study, 290 residents participated; their mean age was 84.3 ± 7.3 years, 82 (28%) were men, and their mean HbA 1c level was 5.7% ± 0.4%. Mean CANRISK score was 29.4 ± 8.0, and of the 254 (88%) considered to be moderate or high risk, 10 (4%) had an HbA 1c level of 6.5% or higher and 49 (19%) had an HbA 1c level of 6.0% or higher. Mean FINDRISC score was 10.8 ± 4.2, and of the 58 (20%) considered to be high or very high risk, 4 (7%) had an HbA 1c level of 6.5% or higher and 15 (26%) had an HbA 1c level of 6.0% or higher. The area under the receiver-operating characteristic curve was 0.57 (95% confidence interval 0.42-0.72) for the CANRISK survey identifying participants with an HbA 1c level of 6.5% or higher and 0.59 (95% confidence interval 0.51-0.67) for identifying participants with an HbA 1c level of 6.0% or higher. Similar characteristics were observed for the FINDRISC survey., Conclusions: In this group of seniors with no known diabetes history, mean HbA 1c level approximated that in the general population and neither survey effectively identified those with elevated blood glucose levels. These findings should be confirmed in a larger study; nevertheless, routine use of these surveys as a diabetes screening strategy does not appear to be warranted at this time., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Legislative changes since 2007 have given Alberta pharmacists additional authorizations and new practice settings, which should enhance provision of clinical services to patients. This study examined whether these changes are related to the number of diabetes management activities provided by pharmacists., Methods: Cross-sectional surveys of Alberta pharmacists were conducted in 2006 and 2015. Both questionnaires contained 63 diabetes management activities, with response options to indicate how frequently the activity was provided. Respondents were grouped by survey year, practice setting, diabetes-specific training and additional authorizations. The number of diabetes management activities provided often or always were compared among groups by using analysis of variance., Results: Data from 128 pharmacists participating in the 2006 survey were compared with 256 pharmacists participating in the 2015 survey; overall mean age was 41.6 (±10.9) years, 245 (64%) were women, mean duration of practice was 16.1 (±11.8) years, 280 (73%) were community pharmacists, 75 (20%) were certified diabetes educators (CDEs), and 100 (26%) had additional prescribing authorization (APA). Pharmacists provided a mean of 28.7 (95% CI 26.3 to 31.2) diabetes management activities in 2006 and 35.2 (95% CI 33.4-37.0) activities in 2015 (p<0.001). Pharmacists who were CDEs provided significantly more activities compared to other pharmacists (p<0.001). In 2015, working in a primary care network and having APA were also associated with provision of more activities (p<0.05 for both comparisons)., Conclusions: Pharmacists provided more diabetes management activities in 2015 than in 2006. The number of diabetes management activities was also associated with being a CDE, working in a primary care network or having APA., (Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Purpose: The objective of this study was to determine if there is a dose-response relationship between sulfonylureas and major adverse cardiovascular events (MACE)., Methods: We conducted a retrospective cohort study among elderly patients with no history of acute coronary syndrome or stroke who initiated gliclazide or glyburide therapy between 1998 and 2010. Gliclazide and glyburide users were evaluated separately, and a high-dimensional propensity score (HDPS) was used to match patients initiating therapy with a low or high dose. A time-dependent variable was used to further characterize exposure, which can change during follow-up. Cox proportional hazard regression models were used to compare the risk of MACE between low (reference) and high doses., Results: We identified 14,213 new users of gliclazide or glyburide (mean age, 74.7 (standard deviation 6.4) years; males, 52.8%; and mean follow-up duration, 2.7 (standard deviation 2.9) years). Among gliclazide users, there was a higher risk of MACE with high compared with low dose (crude rates: 32.8 and 28.2 per 1000 person-years, respectively), but this did not reach statistical significance (HDPS-matched hazard ratio) 1.15; 95% confidence interval (0.96-1.38). For glyburide users, however, MACE occurred more frequently in the high compared with low dose (crude rates: 38.9 and 31.5 per 1000 person-years, respectively; HDPS-matched hazard ratio 1.24; 95% confidence interval 1.02-1.50)., Conclusions: Among new users of sulfonylureas, there appears to be a dose-response relationship between glyburide and MACE, but not for gliclazide. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Previous outcomes-based studies of adherence to diabetes medications have focused on glycemic control and are limited by questions of temporality and uncontrolled confounding., Objective: This retrospective cohort study of new oral antidiabetic medication users examined the effect of adherence on risk of incident macrovascular and microvascular complications., Methods: A nationwide integrated insurance claims and laboratory database was used to identify new oral antidiabetic medication users between January 2004 and December 2009. People with preexisting complications were excluded and the remaining cohort was followed until development of a new diabetes complication or December 2010. Medication adherence was calculated at 3-month intervals and entered as a time-dependent variable in a Cox proportional hazards model. Covariables entered in the model included patient demographics, clinical laboratory data, a medical frailty indicator and a mortality risk score from the Johns Hopkins adjusted clinical groups system, and medication use at baseline., Results: Among the 54 505 included patients, the median age was 60 years, 28 125 (52%) were men, 1447 (3%) were considered frail, the mean mortality risk score was 33.7 (±11.1), and 9793 (18%) developed a new diabetes complication. Good adherence (medication possession ratio ≥0.8) was associated with a lower risk of a new microvascular or macrovascular diabetes complication (adjusted hazard ratio = 0.96; 95% CI = 0.92-1.00; P = 0.05)., Conclusions: This study design addresses limitations of previous studies and found a small but significantly lower risk of new diabetes complications associated with good adherence to oral antidiabetic medications., (© The Author(s) 2016.)

We measure, by photonic torque microscopy, the nonconservative rotational motion arising from the transverse components of the radiation pressure on optically trapped, ultrathin silicon nanowires. Unlike spherical particles, we find that nonconservative effects have a significant influence on the nanowire dynamics in the trap. We show that the extreme shape of the trapped nanowires yields a transverse component of the radiation pressure that results in an orbital rotation of the nanowire about the trap axis. We study the resulting motion as a function of optical power and nanowire length, discussing its size-scaling behavior. These shape-dependent nonconservative effects have implications for optical force calibration and optomechanics with levitated nonspherical particles.

Aims: To examine whether patients using sitagliptin at the time of an acute coronary syndrome event are at increased risk of incident heart failure compared with those not exposed., Methods: Using US claims data, people with diabetes without a history of heart failure in the 3 years before hospitalization for acute coronary syndrome were identified for the period 2004 to 2010. We used a nested case-control design, whereby cases were patients who developed incident heart failure <30 days after admission to hospital for acute coronary syndrome and were matched by age and sex with up to 10 controls with no heart failure. Subjects exposed or not exposed to sitagliptin in the 90 days before acute coronary syndrome admission were compared using conditional logistic regression after adjustment for clinical and laboratory data, healthcare utilization and propensity scores., Results: In total, 457 cases of heart failure developing de novo after diagnosis of acute coronary syndrome were matched to 4570 controls. The average age of the subjects was 55 years and 65% were male. Overall, 11 of 147 (7%) people exposed to sitagliptin developed heart failure compared with 446 of the 4880 people not exposed (9%, adjusted odds ratio 0.75, 95% CI 0.38-1.46; P=0.40). Sitagliptin exposure before acute coronary syndrome was not associated with an increased risk of death or heart failure combined (7% vs 9%, adjusted odds ratio 0.66, 95% CI 0.34-1.28)., Conclusions: In our sample of patients who are at high risk of heart failure after acute coronary syndrome, sitagliptin exposure was not associated with an increased risk of de novo heart failure., (© 2015 Diabetes UK.)

Background: Even in the presence of promising biomedical treatment as prevention, HIV incidence among men who have sex with men has not always decreased. Counseling interventions, therefore, continue to play an important role in reducing HIV sexual transmission behaviors among gay and bisexual men and other men who have sex with men. The present study evaluated effects of a small-group counseling intervention on psychosocial outcomes and HIV sexual risk behavior., Method: HIV-positive (HIV+) peer counselors administered seven 2-hour counseling sessions to groups of 5 to 8 HIV+ gay and bisexual men. The intervention employed information provision, motivational interviewing, and behavioral skills building to reduce sexual transmission risk behaviors., Results: There was a significant reduction in condomless anal sex (CAS) with HIV-negative and unknown HIV-status partners, from 50.0% at baseline to 28.9% of the sample at 3-month follow-up. Findings were robust even when controlling for whether the participant had an undetectable viral load at baseline. Significant reductions were also found in the two secondary psychosocial outcomes, loneliness and sexual compulsivity., Conclusions: The findings provide preliminary evidence that this intervention may offer an efficient way of concurrently reducing CAS and mental health problems, such as sexual compulsivity and loneliness, for HIV+ gay and bisexual men., Trial Registration: ClinicalTrials.gov NCT02546271.

Background: Animal models have demonstrated that sulfonylureas increase the size of myocardial infarction; however, data in humans is scarce. This study evaluated the association between sulfonylurea use and infarct size in diabetes patients with ST-elevation myocardial infarction (STEMI)., Methods: Consecutive STEMI patients admitted in Edmonton, Canada between 2006 and 2011 were enrolled in a regional prospective registry program. Patients with type 2 diabetes were identified from this group and the maximum recorded troponin I (max cTnI) within the first 48 h of chest pain onset was used as the primary outcome to quantify infarct size. The relationship between preadmission sulfonylurea use and max cTnI was assessed using multivariable linear regression to adjust for patient demographics, cardiovascular risk factors, clinical data on admission, ischemia time, reperfusion therapy and preadmission drugs., Results: There were 560 STEMI patients with type 2 diabetes; mean (standard deviation; SD) age was 63.3 (12.8) years, 395 (70.5%) were male, 216 (38.6%) received primary percutaneous intervention, and 211 (37.7%) received thrombolysis. The max cTnI was higher in 146 sulfonylurea users compared to 414 non-sulfonylurea users (mean (SD): 49.8 (74.3) ng/mL versus 39.9 (50.4) ng/mL, respectively; adjusted between-group difference: 12.9 ng/mL; 95% CI 0.3-25.5; p=0.044)., Conclusion: This study adds further evidence to the proposed causal relationship between sulfonylureas and adverse cardiovascular events by observing a significant difference in infarct size among type 2 diabetes patients presenting with STEMI. Clinicians should consider this association when prescribing sulfonylureas to manage patients with type 2 diabetes., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The surface composition and surface tension of aqueous droplets can influence key aerosol characteristics and processes including the critical supersaturation required for activation to form cloud droplets in the atmosphere. Despite its fundamental importance, surface tension measurements on droplets represent a considerable challenge owing to their small volumes. In this work, we utilize holographic optical tweezers to study the damped surface oscillations of a suspended droplet (<10 μm radius) following the controlled coalescence of a pair of droplets and report the first contactless measurements of the surface tension and viscosity of droplets containing only 1-4 pL of material. An advantage of performing the measurement in aerosol is that supersaturated solute states (common in atmospheric aerosol) may be accessed. For pairs of droplets starting at their equilibrium surface composition, surface tensions and viscosities are consistent with bulk equilibrium values, indicating that droplet surfaces respond to changes in surface area on microsecond timescales and suggesting that equilibrium values can be assumed for growing atmospheric droplets. Furthermore, droplet surfaces are shown to be rapidly modified by trace species thereby altering their surface tension. This equilibration of droplet surface tension to the local environmental conditions is illustrated for unknown contaminants in laboratory air and also for droplets exposed to gas passing through a water-ethanol solution. This approach enables precise measurements of surface tension and viscosity over long time periods, properties that currently are poorly constrained.

When a microscopic particle moves through a low Reynolds number fluid, it creates a flow-field which exerts hydrodynamic forces on surrounding particles. In this work we study the 'Lissajous-like' trajectories of an optically trapped 'probe' microsphere as it is subjected to time-varying oscillatory hydrodynamic flow-fields created by a nearby moving particle (the 'actuator'). We show a breaking of time-reversal symmetry in the motion of the probe when the driving motion of the actuator is itself time-reversal symmetric. This symmetry breaking results in a fluid-pumping effect, which arises due to the action of both a time-dependent hydrodynamic flow and a position-dependent optical restoring force, which together determine the trajectory of the probe particle. We study this situation experimentally, and show that the form of the trajectories observed is in good agreement with Stokesian dynamics simulations. Our results are related to the techniques of active micro-rheology and flow measurement, and also highlight how the mere presence of an optical trap can perturb the environment it is in place to measure.

We present a microfluidic chip in Polymethyl methacrylate (PMMA) for optical trapping of particles in an 80µm wide microchannel using two counterpropagating single-mode beams. The trapping fibers are separated from the sample fluid by 70µm thick polymer walls. We calculate the optical forces that act on particles flowing in the microchannel using wave optics in combination with non-sequential ray-tracing and further mathematical processing. Our results are compared with a theoretical model and the Mie theory. We use a novel fabrication process that consists of a premilling step and ultraprecision diamond tooling for the manufacturing of the molds and double-sided hot embossing for replication, resulting in a robust microfluidic chip for optical trapping. In a proof-of-concept demonstration, we show the trapping capabilities of the hot embossed chip by trapping spherical beads with a diameter of 6µm, 8µm and 10µm and use the power spectrum analysis of the trapped particle displacements to characterize the trap strength.

Background: Adding pharmacists to primary care teams significantly improved blood pressure control and reduced predicted 10-year cardiovascular risk in patients with Type 2 diabetes. This pre-specified sub-study evaluated the economic implications of this cardiovascular risk reduction strategy., Methods: One-year outcomes and healthcare utilization data from the trial were used to determine cost-effectiveness from the public payer perspective. Costs were expressed in 2014 Canadian dollars and effectiveness was based on annualized risk of cardiovascular events derived from the UKPDS Risk Engine., Results: The 123 evaluable trial patients included in this analysis had a mean age of 62 ( ± 11) years, 38% were men, and mean diabetes duration was 6 ( ± 7) years. Pharmacists provided 3.0 ( ± 1.9) hours of additional service to each intervention patient, which cost $226 ( ± $1143) per patient. The overall one-year per-patient costs for healthcare utilization were $190 lower in the intervention group compared with usual care [95% confidence interval (CI): -$1040, $668). Intervention patients had a significant 0.3% greater reduction in the annualized risk of a cardiovascular event (95% CI: 0.08%, 0.6%) compared with usual care. In the cost-effectiveness analysis, the intervention dominated usual care in 66% of 10,000 bootstrap replications. At a societal willingness-to-pay of $4000 per 1% reduction in annual cardiovascular risk, the probability that the intervention was cost-effective compared with usual care reached 95%. A sensitivity analysis using multiple imputation to replace missing data produced similar results., Conclusions: Within a randomized trial, adding pharmacists to primary care teams was a cost-effective strategy for reducing cardiovascular risk in patients with Type 2 diabetes. In most circumstances, this intervention may also be cost saving., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

More than 40 years after publication of the University Group Diabetes Program trial, the cardiovascular safety of sulphonylureas is still contentious. Although several hypotheses linking sulphonylureas to adverse cardiovascular effects exist, none provide conclusive evidence. Adding to the controversy, current clinical trials and observational studies provide inconsistent, and sometimes conflicting, evidence for the cardiovascular effects of sulphonylureas. Overall, observational evidence suggests that an increased risk of adverse cardiovascular outcomes is associated with sulphonylureas; however, these data may be subject to residual confounding and bias. Although evidence from randomized controlled trials has suggested a neutral effect, the majority of these studies were not specifically designed to assess the effect of sulphonylureas on adverse cardiovascular event risk. Current ongoing large clinical trials may provide some clarity on the cardiovascular safety of sulphonylureas, but the results are not expected for several years. With the continued uncertainties concerning the cardiovascular safety of all antidiabetic drugs, a clear answer with regard to sulphonylureas is warranted. The objectives of the present article were to provide an overview of the controversy surrounding sulphonylurea-related cardiovascular effects, to discuss the limitations of the current literature, and to provide recommendations for future studies aiming to elucidate the true relationship between sulphonylureas and adverse cardiovascular effects in people with type 2 diabetes., (© 2015 John Wiley & Sons Ltd.)

Objective: To identify which activities produced a significant improvement in blood pressure control in patients with type 2 diabetes when pharmacists were added to primary care teams., Methods: This prespecified, secondary analysis evaluated medication management data from a randomized controlled trial. The primary outcome was a change in treatment, defined as addition, dosage increase, or switching of an antihypertensive medication during the 1-year study period. The secondary outcome was a change in antihypertensive medication adherence using the medication possession ratio (MPR)., Results: The 200 evaluable trial patients had a mean age of 59 (SD, 11) years, 44% were men, and mean blood pressure was 130 (SD, 16)/74 (SD, 10) mm Hg at baseline. Treatment changes occurred in 45 (42%) of 107 patients in the intervention group and 24 (26%) of 93 patients in the control group (RR, 1.63; 95% CI, 1.08-2.46). Addition of a new medication was the most common type of change, occurring in 34 (32%) patients in the intervention group and 17 (18%) patients in the control group (P = 0.029). Adherence to antihypertensive medication was high at baseline (MPR, 93%). Although medication adherence improved in the intervention group (MPR, 97%) and declined in the control group (MPR, 91%), the difference between groups was not significant (P = 0.21)., Conclusion: The observed improvement in blood pressure control when pharmacists were added to primary care teams was likely achieved through antihypertensive treatment changes and not through improvements in antihypertensive medication adherence.

Aim: To evaluate the association between insulin secretagogues and adverse cardiovascular sequelae in type 2 diabetes patients hospitalized for ischemic heart disease (IHD)., Methods: Administrative health records from Alberta, Canada between 1998 and 2010 were used to identify 2,254 gliclazide, 3,289 glyburide and 740 repaglinide users prior to an IHD-related hospitalization. Multivariable Cox regression models were used to compare the 30-day risk of a composite outcome of all-cause mortality or new onset of atrial fibrillation, stroke, heart failure or myocardial infarction according to insulin secretagogue use., Results: Mean (SD) age was 76.1 (6.9) years, and 60.7% were men. The composite outcome occurred in 322 (30.2%) gliclazide users, 455 (28.1%) glyburide users and 81 (23.4%) repaglinide users within 30 days of IHD hospitalization. There were no differences in risk for glyburide use (adjusted hazard ratio [aHR] 0.91; 95% confidence interval [CI] 0.78-1.05) or repaglinide use (aHR 0.80; 95% CI 0.63-1.03) compared to gliclazide. Similar results were observed in analyses for each element of the composite outcome., Conclusions: In older patients with type 2 diabetes hospitalized for IHD, prior use of gliclazide, glyburide, or repaglinide appears to be associated with a similar risk of adverse cardiovascular sequelae., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Our purpose was to measure the effect of non-benefit drug use on observed associations between exposure and outcome, thereby documenting an empirical example of the potential magnitude of biases introduced when exposure status is misclassified from a restrictive drug coverage policy., Methods: New users of antidiabetic agents were identified with a 1-year washout period between January 1, 1995, and December 31, 2005, in Saskatchewan, Canada, and were followed until December 31, 2008. Within this population-based cohort, persons were classified as users of benefit or non-benefit thiazolidinediones (TZDs) according to their first prescription record between January 1, 2006, and December 31, 2006 (non-benefit prescription records were not captured before 2006). An intention-to-treat approach was used to categorize TZD exposure over time. We evaluated the potential bias introduced by drug exposure misclassification by evaluating bootstrapped differences in hazard ratio (HR) estimates of all-cause hospitalization or death between users and nonusers of TZDs obtained from analyses that contained complete drug use (non-benefit and benefit drug use) versus benefit drug use only (non-benefit drug use was misclassified as unexposed). All analyses were replicated within the same cohort of new users of antidiabetic agents for clopidogrel and β-blocker (bisoprolol or carvedilol) users versus nonusers because these agents were also subject to exposure misclassification from non-benefit drug use during the period of the study., Findings: Among 27,333 new users of antidiabetic agents, we identified 5759 TZD users (28% non-benefit) and 21,574 nonusers of TZDs. The crude HR for hospitalization or death among TZD users versus nonusers was higher in a database that contained benefit-only prescriptions than in a database that contained all prescriptions (HR = 1.11 [95% CI, 1.05-1.18] vs HR = 0.99 [95% CI, 0.94-1.04]). However, the differences in HRs after adjustment for demographic characteristics, health care utilization, comorbidities, and medications suggested minimal bias was introduced when TZD exposure was misclassified in the benefit-only database (adjusted HR [aHR] = 1.04 [95% CI. 0.98-1.10] vs aHR = 0.99 [95% CI, 0.94-1.04]; bootstrapped aHR difference = +0.05 [95% CI, 0.02-0.08]). Minimal differences in aHRs were also observed within analyses of clopidogrel (1551 users [24% non-benefit]; bootstrapped aHR difference = +0.01 [95% CI, -0.04 to 0.06]) and β-blocker users (351 users [42% non-benefit]; bootstrapped aHR difference = +0.06 [95% CI, -0.09 to 0.20]) versus nonusers., Implications: Although patient characteristics and outcomes differed between users of non-benefit and benefit drugs, misclassification of drug exposure did not meaningfully bias estimates of all-cause mortality and hospitalization after covariate adjustment in our study., (Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.)